Squamous cell carcinoma arising within a maxillary odontogenic keratocyst: A rare occurrence

PubMed Central

Jalali, Elnaz; Ferneini, Elie M.; Rengasamy, Kandasamy

2017-01-01

Squamous cell carcinoma (SCC) arising within the lining of an odontogenic keratocyst (OKC) is a rare occurrence. Although potentially locally destructive, OKC is a benign odontogenic process that typically presents with clinical and radiographic features characteristic of a benign intraosseous neoplasm. We present the clinical and radiographic features of a maxillary mass that demonstrated SCC arising from the lining of an OKC. Although the initial clinical and radiographic presentation suggested an infection or malignant neoplasm, biopsies revealed an infiltrative well-differentiated SCC contiguous with and arising from the focus of a pre-existing OKC. The patient subsequently underwent a type II hemi-maxillectomy with neoadjuvant chemoradiation. This report discusses the clinical and radiographic features associated with intraosseous malignancies, especially those arising from an otherwise benign odontogenic lesion. While the majority of OKCs are benign, the current report illustrates the potential for carcinomatous transformation within the lining of an OKC. PMID:28680851

Sodium copper chlorophyllin: in vitro digestive stability and accumulation by Caco-2 human intestinal cells.

PubMed

Ferruzzi, Mario G; Failla, Mark L; Schwartz, Steven J

2002-03-27

Sodium copper chlorophyllin (SCC), a mixture of water-soluble chlorophyll derivatives, is used as both a food colorant and a common dietary supplement. Although the potential antimutagenic and antioxidant properties of this commercial preparation have been demonstrated, limited information is available on its digestion and absorption by humans. Stability of SCC was examined during simulated gastric and small intestinal digestion. Three preparations were subjected to in vitro digestion: SCC in water, SCC in water + 10% corn oil, and SCC in applesauce. SCC components from raw material preparations and in digested samples were analyzed by C(18) HPLC with photodiode array detection. Cu(II)chlorin e(4), the major chlorin component of SCC, was relatively stable during simulated digestion. In contrast, greater than 90% of Cu(II)chlorin e(6) was degraded to undetermined products during digestion. Recovery of Cu(II)chlorin e(6) after digestion was increased by incorporation of SCC into applesauce, suggesting a protective role of the inclusion matrix for stabilization of labile SCC components. Accumulation of SCC derivatives was investigated by using differentiated cultures of the TC7 clone of the Caco-2 human intestinal cell line. Cellular accumulation from media containing 0.5 to 60 ppm SCC was linear with intracellular content ranging between 0.2 and 29.6 microg of total SCC per mg of cellular protein. Uptake of SCC by Caco-2 cells was significantly (p < 0.01) lower in cultures incubated at 4 degrees C than in those incubated at 37 degrees C. Although intracellular SCC was transported into both apical and basolateral compartments when Caco-2 cells were grown on inserts, apical efflux was significantly greater (p < 0.01) than basolateral efflux. Stability of Cu(II)chlorin e(4) during in vitro digestion and effective uptake by Caco-2 enterocyte-like cells support the likelihood that a portion of this SCC component or its metabolites is absorbed from the human intestine.

Spheroid Culture of Head and Neck Cancer Cells Reveals an Important Role of EGFR Signalling in Anchorage Independent Survival.

PubMed

Braunholz, Diana; Saki, Mohammad; Niehr, Franziska; Öztürk, Merve; Borràs Puértolas, Berta; Konschak, Robert; Budach, Volker; Tinhofer, Ingeborg

2016-01-01

In solid tumours millions of cells are shed into the blood circulation each day. Only a subset of these circulating tumour cells (CTCs) survive, many of them presumable because of their potential to form multi-cellular clusters also named spheroids. Tumour cells within these spheroids are protected from anoikis, which allows them to metastasize to distant organs or re-seed at the primary site. We used spheroid cultures of head and neck squamous cell carcinoma (HNSCC) cell lines as a model for such CTC clusters for determining the role of the epidermal growth factor receptor (EGFR) in cluster formation ability and cell survival after detachment from the extra-cellular matrix. The HNSCC cell lines FaDu, SCC-9 and UT-SCC-9 (UT-SCC-9P) as well as its cetuximab (CTX)-resistant sub-clone (UT-SCC-9R) were forced to grow in an anchorage-independent manner by coating culture dishes with the anti-adhesive polymer poly-2-hydroxyethylmethacrylate (poly-HEMA). The extent of apoptosis, clonogenic survival and EGFR signalling under such culture conditions was evaluated. The potential of spheroid formation in suspension culture was found to be positively correlated with the proliferation rate of HNSCC cell lines as well as their basal EGFR expression levels. CTX and gefitinib blocked, whereas the addition of EGFR ligands promoted anchorage-independent cell survival and spheroid formation. Increased spheroid formation and growth were associated with persistent activation of EGFR and its downstream signalling component (MAPK/ERK). Importantly, HNSCC cells derived from spheroid cultures retained their clonogenic potential in the absence of cell-matrix contact. Addition of CTX under these conditions strongly inhibited colony formation in CTX-sensitive cell lines but not their resistant subclones. Altogether, EGFR activation was identified as crucial factor for anchorage-independent survival of HNSCC cells. Targeting EGFR in CTC cluster formation might represent an attractive anti-metastatic treatment approach in HNSCC.

Targeting PI3K-AKT-mTOR by LY3023414 inhibits human skin squamous cell carcinoma cell growth in vitro and in vivo.

PubMed

Zou, Ying; Ge, Minggai; Wang, Xuemin

2017-08-19

Abnormal activation of PI3K-AKT-mTOR signaling is detected in human skin squamous cell carcinoma (SCC). LY3023414 is a novel, potent, and orally bio-available PI3K-AKT-mTOR inhibitor. Its activity against human skin SCC cells was tested. We demonstrated that LY3023414 was cytotoxic when added to established (A431 line) and primary (patient-derived) human skin SCC cells. LY3023414 induced G0/1-S arrest and inhibited proliferation of skin SCC cells. Moreover, LY3023414 induced activation of caspase-3/-9 and apoptosis in skin SCC cells. Intriguingly, LY3023414 was yet non-cytotoxic nor pro-apoptotic to normal human skin cells (melanocytes, keratinocytes and fibroblasts). At the molecular level, LY3023414 blocked PI3K-AKT-mTOR activation in skin SCC cells, as it dephosphorylated PI3K-AKT-mTOR substrates: P85, AKT and S6K1. In vivo studies showed that oral administration of LY3023414 at well-tolerated doses inhibited A431 xenograft tumor growth in severe combined immunodeficiency (SCID) mice. AKT-mTOR activation in LY3023414-treated tumors was also largely inhibited. Together, these results suggest that targeting PI3K-AKT-mTOR by LY3023414 inhibits human skin SCC cell growth in vitro and in vivo, establishing the rationale for further clinical testing. Copyright © 2017 Elsevier Inc. All rights reserved.

Distinct profiles of TERT promoter mutations and telomerase expression in head and neck cancer and cervical carcinoma.

PubMed

Annunziata, Clorinda; Pezzuto, Francesca; Greggi, Stefano; Ionna, Franco; Losito, Simona; Botti, Gerardo; Buonaguro, Luigi; Buonaguro, Franco M; Tornesello, Maria Lina

2018-03-31

Two recurrent mutations (-124 G > A and -146 G > A) in the core promoter region of the human telomerase reverse transcriptase (TERT) gene create consensus binding sites for ETS transcription factors and cause increased TERT expression in several tumour types. We analyzed TERT promoter mutations and TERT mRNA levels in head and neck cancer, cervical carcinoma and cervical intraepithelial neoplasia (CIN) as well as in C-4I, CaSki, HeLa and SiHa cervical cell lines. Nucleotide sequence analysis of TERT promoter region showed that 33.3% of oral squamous cell carcinoma (SCC) and 16.8% of cervical SCC harboured mutually exclusive G to A transitions at nucleotide position -124 or -146. TERT promoter was mutated at nucleotide -146 (G > A) in SiHa cell line. Other nucleotide changes creating in some cases putative ETS binding sites were more frequent in oral SCC (26.7%) than in cervical carcinoma (4.8%). The frequency of mutations was independent of human papillomavirus (HPV) tumour status in both cervical and oral cancer. Expression of TERT gene was significantly higher in TERT promoter mutated (-124G > A or -146G > A) cervical SCC compared to not mutated SCC irrespective of HPV16 E6 and E7 levels. Such hot spot changes were not detected in oropharyngeal SCC, cervical adenocarcinoma and CIN lesions. Our results suggest that TERT promoter mutations play a relevant role in oral SCC as well as in cervical SCC, besides the already known effect of HPV16 E6 protein on TERT expression. © 2018 UICC.

DNA methylation regulated microRNAs in HPV-16-induced head and neck squamous cell carcinoma (HNSCC).

PubMed

Sannigrahi, M K; Sharma, Rajni; Singh, Varinder; Panda, Naresh K; Rattan, Vidya; Khullar, Madhu

2018-02-17

Epigenetic modifications have been reported to play an important role in regulating gene expression and these modifications become critical when they have a role in controlling another important layer of epigenetic regulation namely microRNAs. In the present study, we have identified the microRNAs that may be regulated by promoter DNA methylation and histone acetylation in Human papilloma virus-positive head and neck squamous cell carcinoma. HPV-negative cell line (UPCI:SCC-116) and HPV-16 +ve cell line (UPCI:SCC-090) were treated with methylation inhibitor (5-aza-2'-deoxycytidine, AZA) and acetylation inhibitor (Trichostatin-A, TSA), followed by micro-array analysis. The differentially expressed miRNAs were validated in control (n = 10), HPV-16 +ve (n = 30), and HPV -ve (n = 30) HNC, TCGA (n = 529) tissue samples, and two HPV -ve (SCC116 and Hacat) and two HPV +ve (SCC090 and SiHa) cell lines. Methylation-specific PCR (MSP) and chromatin immunoprecipitation assay (CHIP) were performed to validate their regulation. In silico and in vitro analyses of identified miRNAs were done to study putative pathways they target and their possible role in carcinogenesis. Among 10 miRNAs specifically up-regulated in microarray analysis of AZA-treated SCC090 cells, we observed significantly decreased expression of hsa-miR-181c-5p, hsa-miR-132-5p, hsa-miR-658 in HPV +ve HNC cohort, TCGA tissue samples, and cell lines as compared to their HPV -ve counterpart, and their promoter region also possesses CpG islands. MSP and analysis of TCGA data (MethHC) revealed increased frequency of methylation at the promoter of hsa-miR-132-5p that is negatively correlated with its expression. In TSA-treated SCC090 cells, out of 7 miRNAs, two namely Hsa-miR-129-2-3p and Hsa-miR-449a were found to be up-regulated as compared to HPV -ve cells. However, the levels of enrichment by anti-acetyl-H3 and anti-acetyl-H4 were significantly low in cell lines compared to respective controls and both were up-regulated in HPV +ve compared to HPV -ve TCGA tissue samples. In silico analysis revealed hsa-miR-132-5p targeted canonical β-catenin/wnt pathway and modulation of down-stream genes of the pathway was observed on over-expression/inhibition of hsa-miR-132-5p. This study suggests the role of epigenetic modifications in regulating expression of miRNAs in HPV +ve HNSCC.

Epidermal growth factor receptor inhibition by anti-CD147 therapy in cutaneous squamous cell carcinoma.

PubMed

Frederick, John W; Sweeny, Larissa; Hartman, Yolanda; Zhou, Tong; Rosenthal, Eben L

2016-02-01

Advanced cutaneous squamous cell carcinoma (SCC) is an uncommon and aggressive malignancy. As a result, there is limited understanding of its biology and pathogenesis. CD147 and epidermal growth factor receptor (EGFR) have been identified as oncologically important targets, but their relationship remains undefined in cutaneous SCC. Multiple cutaneous SCC cell lines (Colo-16, SRB-1, and SRB-12), were treated in vitro with a range of chimeric anti-CD147 monoclonal antibody (mAb) (0, 50, 100, and 200 µg/mL) or transfected with a small interfering RNA against CD147 (SiCD147). Cell proliferation, migration (scratch wound healing assay), and protein expression was then assessed. In vivo, Colo-16 flank xenografts were treated anti-CD147 mAb (150 µg i.p. triweekly). After treatment with anti-CD147 (200 µg/mL), there was a significant decrease in proliferation for all cell lines relative to controls (p < .005). In addition, treatment with anti-CD147 (200 µg/mL) resulted in decreased cell migration for all cell lines, with an average of 43% reduction in closure compared to controls (p < .001). Colo-16 SiCD147 expression demonstrated similar reduction in proliferation and wound closure. Anti-CD147 antibody therapy and siRNA mediated reduction in CD147 expression were both found to decrease protein expression of EGFR, which correlated with a reduction in downstream total and phosphorylated protein kinase B (pAKT). Tumor growth in vivo was reduced for both the anti-CD147 treatment group and the SiCD147 group relative to controls. Inhibition and downregulation of CD147 in cutaneous SCC resulted in suppression of the malignant phenotype in vitro and in vivo, which may be mediated in part by an alteration in EGFR expression. As a result, CD147 may serve as a potential therapeutic target for advanced cutaneous SCC. © 2014 Wiley Periodicals, Inc.

SOX2 and p63 colocalize at genetic loci in squamous cell carcinomas

PubMed Central

Watanabe, Hideo; Ma, Qiuping; Peng, Shouyong; Adelmant, Guillaume; Swain, Danielle; Song, Wenyu; Fox, Cameron; Francis, Joshua M.; Pedamallu, Chandra Sekhar; DeLuca, David S.; Brooks, Angela N.; Wang, Su; Que, Jianwen; Rustgi, Anil K.; Wong, Kwok-kin; Ligon, Keith L.; Liu, X. Shirley; Marto, Jarrod A.; Meyerson, Matthew; Bass, Adam J.

2014-01-01

The transcription factor SOX2 is an essential regulator of pluripotent stem cells and promotes development and maintenance of squamous epithelia. We previously reported that SOX2 is an oncogene and subject to highly recurrent genomic amplification in squamous cell carcinomas (SCCs). Here, we have further characterized the function of SOX2 in SCC. Using ChIP-seq analysis, we compared SOX2-regulated gene profiles in multiple SCC cell lines to ES cell profiles and determined that SOX2 binds to distinct genomic loci in SCCs. In SCCs, SOX2 preferentially interacts with the transcription factor p63, as opposed to the transcription factor OCT4, which is the preferred SOX2 binding partner in ES cells. SOX2 and p63 exhibited overlapping genomic occupancy at a large number of loci in SCCs; however, coordinate binding of SOX2 and p63 was absent in ES cells. We further demonstrated that SOX2 and p63 jointly regulate gene expression, including the oncogene ETV4, which was essential for SOX2-amplified SCC cell survival. Together, these findings demonstrate that the action of SOX2 in SCC differs substantially from its role in pluripotency. The identification of the SCC-associated interaction between SOX2 and p63 will enable deeper characterization the downstream targets of this interaction in SCC and normal squamous epithelial physiology. PMID:24590290

SOX2 and p63 colocalize at genetic loci in squamous cell carcinomas.

PubMed

Watanabe, Hideo; Ma, Qiuping; Peng, Shouyong; Adelmant, Guillaume; Swain, Danielle; Song, Wenyu; Fox, Cameron; Francis, Joshua M; Pedamallu, Chandra Sekhar; DeLuca, David S; Brooks, Angela N; Wang, Su; Que, Jianwen; Rustgi, Anil K; Wong, Kwok-kin; Ligon, Keith L; Liu, X Shirley; Marto, Jarrod A; Meyerson, Matthew; Bass, Adam J

2014-04-01

The transcription factor SOX2 is an essential regulator of pluripotent stem cells and promotes development and maintenance of squamous epithelia. We previously reported that SOX2 is an oncogene and subject to highly recurrent genomic amplification in squamous cell carcinomas (SCCs). Here, we have further characterized the function of SOX2 in SCC. Using ChIP-seq analysis, we compared SOX2-regulated gene profiles in multiple SCC cell lines to ES cell profiles and determined that SOX2 binds to distinct genomic loci in SCCs. In SCCs, SOX2 preferentially interacts with the transcription factor p63, as opposed to the transcription factor OCT4, which is the preferred SOX2 binding partner in ES cells. SOX2 and p63 exhibited overlapping genomic occupancy at a large number of loci in SCCs; however, coordinate binding of SOX2 and p63 was absent in ES cells. We further demonstrated that SOX2 and p63 jointly regulate gene expression, including the oncogene ETV4, which was essential for SOX2-amplified SCC cell survival. Together, these findings demonstrate that the action of SOX2 in SCC differs substantially from its role in pluripotency. The identification of the SCC-associated interaction between SOX2 and p63 will enable deeper characterization the downstream targets of this interaction in SCC and normal squamous epithelial physiology.

Analysis of DNA methylation and gene expression in radiation-resistant head and neck tumors.

PubMed

Chen, Xiaofei; Liu, Liang; Mims, Jade; Punska, Elizabeth C; Williams, Kristin E; Zhao, Weiling; Arcaro, Kathleen F; Tsang, Allen W; Zhou, Xiaobo; Furdui, Cristina M

2015-01-01

Resistance to radiation therapy constitutes a significant challenge in the treatment of head and neck squamous cell cancer (HNSCC). Alteration in DNA methylation is thought to play a role in this resistance. Here, we analyzed DNA methylation changes in a matched model of radiation resistance for HNSCC using the Illumina HumanMethylation450 BeadChip. Our results show that compared to radiation-sensitive cells (SCC-61), radiation-resistant cells (rSCC-61) had a significant increase in DNA methylation. After combining these results with microarray gene expression data, we identified 84 differentially methylated and expressed genes between these 2 cell lines. Ingenuity Pathway Analysis revealed ILK signaling, glucocorticoid receptor signaling, fatty acid α-oxidation, and cell cycle regulation as top canonical pathways associated with radiation resistance. Validation studies focused on CCND2, a protein involved in cell cycle regulation, which was identified as hypermethylated in the promoter region and downregulated in rSCC-61 relative to SCC-61 cells. Treatment of rSCC-61 and SCC-61 with the DNA hypomethylating agent 5-aza-2'deoxycitidine increased CCND2 levels only in rSCC-61 cells, while treatment with the control reagent cytosine arabinoside did not influence the expression of this gene. Further analysis of HNSCC data from The Cancer Genome Atlas found increased methylation in radiation-resistant tumors, consistent with the cell culture data. Our findings point to global DNA methylation status as a biomarker of radiation resistance in HNSCC, and suggest a need for targeted manipulation of DNA methylation to increase radiation response in HNSCC.

5-Fluorouracil-induced apoptosis in cultured oral cancer cells.

PubMed

Tong, D; Poot, M; Hu, D; Oda, D

2000-03-01

Chemotherapy is commonly used to treat advanced oral squamous cell carcinoma (SCC) and is known to kill cancer cells through apoptosis. Our hypothesis states that 5-fluorouracil (5FU) also kills cultured oral epithelial cells through programmed cell death or apoptosis. Cultured oral cancer cells were exposed to an optimum dose of 20 mg/ml of 5FU. Cells were analyzed for changes in cell cycle distribution and induction of cell death including apoptosis. Normal control, human papilloma virus-immortalized (PP), ATCC SCC cell line (CA1) and two primary oral SCC cell lines (CA3 and -4) were studied. Inhibition of apoptosis by a pan-caspase inhibitor was used. SYTO 11 flow cytometry showed increased apoptosis in all 5FU-treated cell cultures compared to untreated controls. The results show biological variation in apoptotic response. CA1 had the lowest apoptotic rate of the cancer cell lines at 1.5%. Next lowest was CA3, followed by CA4 and PP. In addition, alteration in the G1 and S phase fractions were found. Untreated CA1 showed 28% G1, 53% S compared to 43% G1, and 40% S of treated. We investigated the pathway of apoptosis using the pan-caspase inhibitor IDN-1529 by methylthiazolyl diphenyl tetrazolium bromide (MTT) colorimetric analysis. Results showed mild inhibition of cell death when cells were incubated with 50 microM IDN-1529 for 24 h. This suggests a probable caspase-dependent apoptotic pathway. In conclusion, our data suggest that 5FU induces oral cancer cell death through apoptosis and that biological variation exists between normal and cancer cells and between different types of cancer cells themselves. Our data indicate that cultures of a useful in vitro model for chemosensitivity assays are possible. Our results also suggest a caspase-dependent pathway for chemocytotoxicity in oral SCC.

Cellular intrinsic factors involved in the resistance of squamous cell carcinoma to photodynamic therapy.

PubMed

Gilaberte, Yolanda; Milla, Laura; Salazar, Nerea; Vera-Alvarez, Jesús; Kourani, Omar; Damian, Alejandra; Rivarola, Viviana; Roca, Maria José; Espada, Jesús; González, Salvador; Juarranz, Angeles

2014-09-01

Photodynamic therapy (PDT) is widely used to treat non-melanoma skin cancer. However, some patients affected with squamous cell carcinoma (SCC) do not respond adequately to PDT with methyl-δ-aminolevulinic acid (MAL-PDT) and the tumors acquire an infiltrative phenotype and became histologically more aggressive, less differentiated, and more fibroblastic. To search for potential factors implicated in SCC resistance to PDT, we have used the SCC-13 cell line (parental) and resistant SCC-13 cells obtained by repeated MAL-PDT treatments (5th and 10th PDT-resistant generations). Xenografts assays in immunodeficient mice showed that the tumors generated by resistant cells were bigger than those induced by parental cells. Comparative genomic hybridization array (aCGH) showed that the three cell types presented amplicons in 3p12.1 CADM2, 7p11.2 EFGR, and 11q13.3 CCND1 genes. The 5th and 10th PDT-resistant cells showed an amplicon in 5q11.2 MAP3K1, which was not present in parental cells. The changes detected by aCGH on CCND1, EFGR, and MAP3K1 were confirmed in extracts of SCC-13 cells by reverse-transcriptase PCR and by western blot, and by immunohistochemistry in human biopsies from persistent tumors after MAL-PDT. Our data suggest that genomic imbalances related to CCND1, EFGR, and particularly MAP3K1 seem to be involved in the development of the resistance of SCC to PDT.

Anticancer drugs and the regulation of Hedgehog genes GLI1 and PTCH1, a comparative study in nonmelanoma skin cancer cell lines.

PubMed

Olesen, Uffe H; Bojesen, Sophie; Gehl, Julie; Haedersdal, Merete

2017-11-01

Nonmelanoma skin cancer is the most common cancer in humans, comprising mainly basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). BCC proliferation is highly dependent on the Hedgehog signaling pathway. We aimed to investigate a panel of anticancer drugs with known activity against skin cancer for their therapeutic potential in localized, enhanced topical treatment of SCC and BCC. Cytotoxicity profiles for vismodegib, 5-fluorouracil (5-FU), methotrexate (MTX), cisplatin, bleomycin, and vorinostat were established in terms of half maximal inhibitory concentration values in a panel of immortalized keratinocytes (HaCaT), BCC (UWBCC1 and BCC77015), and SCC (A431 and SCC25) cell lines. The impact of treatment on the regulation of Hedgehog pathway target genes (GLI1 and PTCH1), measured by real-time PCR, was compared between UWBCC1 and HaCaT. Varying cell line sensitivity profiles to the examined anticancer drugs were observed. Generally, 24-h drug exposure was sufficient to reduce cell viability. We found that 5-FU, MTX, and cisplatin significantly downregulated the expression of two genes controlled by the Hedgehog pathway (≤25-, 2.9-, and 12.5-fold, respectively, for GLI1 in UWBCC1 cells at 48 h, P<0.0001). The gene regulation showed clear concentration dependence and correlated with cytotoxicity for both 5-FU and MTX. We find a potential for the use of anticancer drugs in localized and enhanced topical treatment of nonmelanoma skin cancer. Of importance in the clinical setting, 24-h drug exposure may be sufficient for significant cytotoxicity for vismodegib, 5-FU, cisplatin, and bleomycin. MTX, 5-FU, and cisplatin may offer particular promise through combined cytotoxicity and downregulation of Hedgehog pathway genes GLI1 and PTCH1.

Cellular and Tumor Radiosensitivity is Correlated to Epidermal Growth Factor Receptor Protein Expression Level in Tumors Without EGFR Amplification;Epidermal growth factor receptor; Radiotherapy; Squamous cell carcinoma; Biomarker; Local tumor control

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kasten-Pisula, Ulla; Saker, Jarob; Eicheler, Wolfgang

2011-07-15

Purpose: There is conflicting evidence for whether the expression of epidermal growth factor receptor in human tumors can be used as a marker of radioresponse. Therefore, this association was studied in a systematic manner using squamous cell carcinoma (SCC) cell lines grown as cell cultures and xenografts. Methods and Materials: The study was performed with 24 tumor cell lines of different tumor types, including 10 SCC lines, which were also investigated as xenografts on nude mice. Egfr gene dose and the length of CA-repeats in intron 1 were determined by polymerase chain reaction, protein expression in vitro by Western blotmore » and in vivo by enzyme-linked immunosorbent assay, and radiosensitivity in vitro by colony formation. Data were correlated with previously published tumor control dose 50% data after fractionated irradiation of xenografts of the 10 SCC. Results: EGFR protein expression varies considerably, with most tumor cell lines showing moderate and only few showing pronounced upregulation. EGFR upregulation could only be attributed to massive gene amplification in the latter. In the case of little or no amplification, in vitro EGFR expression correlated with both cellular and tumor radioresponse. In vivo EGFR expression did not show this correlation. Conclusions: Local tumor control after the fractionated irradiation of tumors with little or no gene amplification seems to be dependent on in vitro EGFR via its effect on cellular radiosensitivity.« less

Optimising intratumoral treatment of head and neck squamous cell carcinoma models with the diterpene ester Tigilanol tiglate.

PubMed

Barnett, Catherine M E; Broit, Natasa; Yap, Pei-Yi; Cullen, Jason K; Parsons, Peter G; Panizza, Benedict J; Boyle, Glen M

2018-04-18

The five-year survival rate for patients with head and neck squamous cell carcinoma (HNSCC) has remained at ~50% for the past 30 years despite advances in treatment. Tigilanol tiglate (TT, also known as EBC-46) is a novel diterpene ester that induces cell death in HNSCC in vitro and in mouse models, and has recently completed Phase I human clinical trials. The aim of this study was to optimise efficacy of TT treatment by altering different administration parameters. The tongue SCC cell line (SCC-15) was identified as the line with the lowest efficacy to treatment. Subcutaneous xenografts of SCC-15 cells were grown in BALB/c Foxn1 nu and NOD/SCID mice and treated with intratumoral injection of 30 μg TT or a vehicle only control (40% propylene glycol (PG)). Greater efficacy of TT treatment was found in the BALB/c Foxn1 nu mice compared to NOD/SCID mice. Immunohistochemical analysis indicated a potential role of the host's innate immune system in this difference, specifically neutrophil infiltration. Neither fractionated doses of TT nor the use of a different excipiant led to significantly increased efficacy. This study confirmed that TT in 40% PG given intratumorally as a single bolus dose was the most efficacious treatment for a tongue SCC mouse model.

Culture of human mesenchymal stem cells using a candidate pharmaceutical grade xeno-free cell culture supplement derived from industrial human plasma pools.

PubMed

Díez, José M; Bauman, Ewa; Gajardo, Rodrigo; Jorquera, Juan I

2015-03-13

Fetal bovine serum (FBS) is an animal product used as a medium supplement. The animal origin of FBS is a concern if cultured stem cells are to be utilized for human cell therapy. Therefore, a substitute for FBS is desirable. In this study, an industrial, xeno-free, pharmaceutical-grade supplement for cell culture (SCC) under development at Grifols was tested for growth of human mesenchymal stem cells (hMSCs), cell characterization, and differentiation capacity. SCC is a freeze-dried product obtained through cold-ethanol fractionation of industrial human plasma pools from healthy donors. Bone marrow-derived hMSC cell lines were obtained from two commercial suppliers. Cell growth was evaluated by culturing hMSCs with commercial media or media supplemented with SCC or FBS. Cell viability and cell yield were assessed with an automated cell counter. Cell surface markers were studied by indirect immunofluorescence assay. Cells were cultured then differentiated into adipocytes, chondrocytes, osteoblasts, and neurons, as assessed by specific staining and microscopy observation. SCC supported the growth of commercial hMSCs. Starting from the same number of seeded cells in two consecutive passages of culture with medium supplemented with SCC, hMSC yield and cell population doubling time were equivalent to the values obtained with the commercial medium and was consistent among lots. The viability of hMSCs was higher than 90%, while maintaining the characteristic phenotype of undifferentiated hMSCs (positive for CD29, CD44, CD90, CD105, CD146, CD166 and Stro-1; negative for CD14 and CD19). Cultured hMSCs maintained the potential for differentiation into adipocytes, chondrocytes, osteoblasts, and neurons. The tested human plasma-derived SCC sustains the adequate growth of hMSCs, while preserving their differentiation capacity. SCC can be a potential candidate for cell culture supplement in advanced cell therapies.

Antitumoral Effect of Hibiscus sabdariffa on Human Squamous Cell Carcinoma and Multiple Myeloma Cells.

PubMed

Malacrida, Alessio; Maggioni, Daniele; Cassetti, Arianna; Nicolini, Gabriella; Cavaletti, Guido; Miloso, Mariarosaria

2016-10-01

Cancer is a leading cause of death worldwide. Despite therapeutic improvements, some cancers are still untreatable. Recently there has been an increasing interest in the use of natural substances for cancer prevention and treatment. Hibiscus sabdariffa (HS) is a plant, belonging to Malvaceae family, widespread in South Asia and Central Africa. HS extract (HSE) used in folk medicine, gained researchers' interest thanks to its antioxidant, anti-inflammatory, and chemopreventive properties. In the present study, we initially assessed HSE effect on a panel of human tumor cell lines. Then we focused our study on the following that are most sensitive to HSE action cell lines: Multiple Myeloma (MM) cells (RPMI 8226) and Oral Squamous Cell Carcinoma (OSCC) cells (SCC-25). In both RPMI 8226 and SCC-25 cells, HSE impaired cell growth, exerted a reversible cytostatic effect, and reduced cell motility and invasiveness. We evaluated the involvement of MAPKs ERK1/2 and p38 in HSE effects by using specific inhibitors, U0126 and SB203580, respectively. For both SCC-25 and RPMI 8226, HSE cytostatic effect depends on p38 activation, whereas ERK1/2 modulation is crucial for cell motility and invasiveness. Our results suggest that HSE may be a potential therapeutic agent against MM and OSCC.

Super-Enhancer-Driven Long Non-Coding RNA LINC01503, Regulated by TP63, Is Over-Expressed and Oncogenic in Squamous Cell Carcinoma.

PubMed

Xie, Jian-Jun; Jiang, Yan-Yi; Jiang, Yuan; Li, Chun-Quan; Lim, Mei-Chee; An, Omer; Mayakonda, Anand; Ding, Ling-Wen; Long, Lin; Sun, Chun; Lin, Le-Hang; Chen, Li; Wu, Jian-Yi; Wu, Zhi-Yong; Cao, Qi; Fang, Wang-Kai; Yang, Wei; Soukiasian, Harmik; Meltzer, Stephen J; Yang, Henry; Fullwood, Melissa; Xu, Li-Yan; Li, En-Min; Lin, De-Chen; Koeffler, H Phillip

2018-06-01

Long non-coding RNAs (lncRNAs) are expressed in tissue-specific pattern, but it is not clear how these are regulated. We aimed to identify squamous cell carcinoma (SCC)-specific lncRNAs and investigate mechanisms that control their expression and function. We studied expression patterns and functions of 4 SCC-specific lncRNAs. We obtained 113 esophageal SCC (ESCC) and matched non-tumor esophageal tissues from a hospital in Shantou City, China, and performed quantitative reverse transcription polymerase chain reaction assays to measure expression levels of LINC01503. We collected clinical data from patients and compared expression levels with survival times. LINC01503 was knocked down using small interfering RNAs and oligonucleotides in TE7, TE5, and KYSE510 cell lines and overexpressed in KYSE30 cells. Cells were analyzed by chromatin immunoprecipitation sequencing, luciferase reporter assays, colony formation, migration and invasion, and mass spectrometry analyses. Cells were injected into nude mice and growth of xenograft tumors was measured. LINC01503 interaction with proteins was studied using fluorescence in situ hybridization, RNA pulldown, and RNA immunoprecipitation analyses. We identified a lncRNA, LINC01503, which is regulated by a super enhancer and is expressed at significantly higher levels in esophageal and head and neck SCCs than in non-tumor tissues. High levels in SCCs correlated with shorter survival times of patients. The transcription factor TP63 bound to the super enhancer at the LINC01503 locus and activated its transcription. Expression of LINC01503 in ESCC cell lines increased their proliferation, colony formation, migration, and invasion. Knockdown of LINC01503 in SCC cells reduced their proliferation, colony formation, migration, and invasion, and the growth of xenograft tumors in nude mice. Expression of LINC01503 in ESCC cell lines reduced ERK2 dephosphorylation by DUSP6, leading to activation of ERK signaling via MAPK. LINC01503 disrupted the interaction between EBP1 and the p85 subunit of PI3K, increasing AKT signaling. We identified an lncRNA, LINC01503, which is increased in SCC cells compared with non-tumor cells. Increased expression of LINC01503 promotes ESCC cell proliferation, migration, invasion, and growth of xenograft tumors. It might be developed as a biomarker of aggressive SCCs in patients. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

Establishment and characterization of a penile cancer cell line, penl1, with a deleterious TP53 mutation as a paradigm of HPV-negative penile carcinogenesis.

PubMed

Chen, Jieping; Yao, Kai; Li, Zaishang; Deng, Chuangzhong; Wang, Liangjiao; Yu, Xingsu; Liang, Peili; Xie, Qiankun; Chen, Peng; Qin, Zike; Ye, Yunlin; Liu, Zhuowei; Zhou, Fangjian; Zhang, Zhenfeng; Han, Hui

2016-08-09

To establish penile cancer (PeCa) cell lines for the study of molecular mechanisms of carcinogenesis and testing therapeutic reagents. We successfully established two PeCa cell lines from fresh tumor tissues from 21 cases. One cell line named Penl1 was isolated from a lymph node metastasis (LNM) of penile squamous cell carcinoma (PeSCC), usual type and comprehensively characterized here. Our in-depth characterization analysis of the Penl1 cell line included morphology, tumorigenicity, genetic characteristics, protein expression, biology, and chemosensitivity. Penl1 was authenticated by single tandem repeat (STR) DNA typing. Comparative histomorphology, genetic characteristics, and protein expression patterns revealed essential similarities between the cell line and its corresponding LNM. In-depth characterization analysis of Penl1 cell line revealed tumorigenicity in immunodeficient mice, negative human papilloma virus (HPV) and mycoplasma infection, TP53 mutations and sensitivity to cisplatin and epirubicin. STR DNA typing did not match any cell lines within three international cell banks. The limitation of this study is that one patient cannot represent the complete heterogeneity of PeCa, especially primary tumor. We established and characterized an HPV-negative and moderately differentiated PeCa cell model with a TP53 missense mutation from a PeSCC, usual type patient. A preliminarily study of carcinogenesis and chemosensitivity suggests that this cell model carries a tumor suppressor gene mutation and is sensitive to chemotherapy drugs.

Establishment and characterization of a penile cancer cell line, penl1, with a deleterious TP53 mutation as a paradigm of HPV-negative penile carcinogenesis

PubMed Central

Li, Zaishang; Deng, Chuangzhong; Wang, Liangjiao; Yu, Xingsu; Liang, Peili; Xie, Qiankun; Chen, Peng; Qin, Zike; Ye, Yunlin; Liu, Zhuowei; Zhou, Fangjian; Zhang, Zhenfeng; Han, Hui

2016-01-01

Purpose To establish penile cancer (PeCa) cell lines for the study of molecular mechanisms of carcinogenesis and testing therapeutic reagents. Materials and Methods We successfully established two PeCa cell lines from fresh tumor tissues from 21 cases. One cell line named Penl1 was isolated from a lymph node metastasis (LNM) of penile squamous cell carcinoma (PeSCC), usual type and comprehensively characterized here. Our in-depth characterization analysis of the Penl1 cell line included morphology, tumorigenicity, genetic characteristics, protein expression, biology, and chemosensitivity. Penl1 was authenticated by single tandem repeat (STR) DNA typing. Results Comparative histomorphology, genetic characteristics, and protein expression patterns revealed essential similarities between the cell line and its corresponding LNM. In-depth characterization analysis of Penl1 cell line revealed tumorigenicity in immunodeficient mice, negative human papilloma virus (HPV) and mycoplasma infection, TP53 mutations and sensitivity to cisplatin and epirubicin. STR DNA typing did not match any cell lines within three international cell banks. The limitation of this study is that one patient cannot represent the complete heterogeneity of PeCa, especially primary tumor. Conclusions We established and characterized an HPV-negative and moderately differentiated PeCa cell model with a TP53 missense mutation from a PeSCC, usual type patient. A preliminarily study of carcinogenesis and chemosensitivity suggests that this cell model carries a tumor suppressor gene mutation and is sensitive to chemotherapy drugs. PMID:27351128

Acacia catechu Ethanolic Seed Extract Triggers Apoptosis of SCC-25 Cells.

PubMed

Lakshmi, Thangavelu; Ezhilarasan, Devaraj; Nagaich, Upendra; Vijayaragavan, Rajagopal

2017-10-01

Acacia catechu Willd ( Fabaceae ), commonly known as catechu, cachou, and black cutch, has been studied for its hepatoprotective, antipyretic, antidiarrheal, hypoglycemic, anti-inflammatory, immunomodulatory, antinociceptive, antimicrobial, free radical scavenging, and antioxidant activities. We evaluated the cytotoxic activity of ethanol extract of A. catechu seed (ACS) against SCC-25 human oral squamous carcinoma cell line. Cytotoxic effect of ACS extract was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, using concentrations of 0.1-1000 μg/mL for 24 h. A. catechu ethanol seed extract was treated SCC-25 cells with 25 and 50 μg/mL. At the end of treatment period, apoptotic marker gene expressions such as caspase 8, 9, Bcl-2, Bax, and cytochrome c were evaluated by semiquantitative reverse transcription-polymerase chain reaction. Morphological changes of ACS treated SCC-25 cells was evaluated by acridine orange/ethidium bromide (AO/EB) dual staining. Nuclear morphology and DNA fragmentation was evaluated by propidium iodide (PI) staining. A. catechu ethanol seed extract treatment caused cytotoxicity in SCC-25 cells with an IC 50 value of 100 μg/mL. Apoptotic markers caspases 8 and 9, cytochrome c, Bax gene expressions were significantly increased upon ACS extract treatment indicate the apoptosis induction in SCC-25 cells. This treatment also caused significant downregulation of Bcl-2 gene expression. Staining with AO/EB and PI shows membrane blebbing, and nuclear membrane distortion further confirms the apoptosis induction by ACS treatment in SCC-25 cells. The ethanol seed extracts of A. catechu was found to be cytotoxic at lower concentrations and induced apoptosis in human oral squamous carcinoma SCC-25 cells. Acacia catechu ethanolic seed extract contains phytochemicals such as epicatechin, rutin, and quercetin Acacia catechu seed (ACS) extract significantly ( P < 0.001) inhibits the active proliferation of human oral squamous carcinoma (SCC-25) cellsACS extract treatment to SCC-25 cells significantly modulated the gene expressions pertaining to apoptosis and propidium iodide and acridine orange/ethidium bromide staining also confirm the apoptosis inductionAntiproliferative and apoptosis inducing activities of ACS extract is correlated with phytochemical contents. Abbreviations used: ACS: Acacia catechu seed extract; MTT: 3 (4,5 dimethylthiazol 2 yl) 2,5 diphenyltetrazolium bromide; DMSO: Dimethyl sulfoxide; AO/EO: Acridine orange/ethidium bromide; LC MS: Liquid chromatography mass spectrometry.

Radiation Response in Two HPV-Infected Head-and-Neck Cancer Cell Lines in Comparison to a Non-HPV-Infected Cell Line and Relationship to Signaling Through AKT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gupta, Anjali K.; Lee, John H.; Wilke, Werner W.

2009-07-01

Purpose: Human papilloma virus (HPV)-associated cancers of the head and neck (H and N) are increasing in frequency and are often treated with radiation. There are conflicting data in the literature regarding the radiation response in the presence of HPV infection, with some data suggesting they may be more sensitive to radiation. There are few studies looking at in vitro effects of HPV and further sensitization by inhibitors of specific signaling pathways. We are in the process of starting a clinical trial in H and N cancer patients using nelfinavir (NFV) (which inhibits Akt) and it would be important tomore » know the effect of HPV on radiation response {+-} NFV. Methods and Materials: Two naturally infected HPV-16 cell lines (UPCI-SCC90 and UMSCC47) and the HPV-negative SQ20B H and N squamous carcinoma cells were used. Western blots with or without 10 uM NFV were done to evaluate signaling from the PI3K-Akt pathway. Clonogenic assays were done in the three cell lines with or without NFV. Results: Both UPCI-SCC90 and UMSCC47 cells were sensitive to radiation as compared with SQ20B and the degree corresponded to Akt activation. The SQ20B cell line has an activating mutation in EGFR resulting in phosphorylation (P) of Akt; UMSCC47 has decreased P-phosphatase and TENsin (PTEN), resulting in increased P-Akt; UPCI-SCC90 had overexpression of P-PTEN and decreased P-Akt. NFV resulted in downregulation of Akt in all three cell lines, resulting in sensitization to radiation. Conclusions: HPV-infected H and N cancers are sensitive to radiation. The degree of sensitivity correlates to Akt activation and they can be further sensitized by NFV00.« less

Effects of neratinib and combination with irradiation and chemotherapy in head and neck cancer cells.

PubMed

Schneider, S; Thurnher, D; Kadletz, L; Seemann, R; Brunner, M; Kotowski, U; Schmid, R; Lill, C; Heiduschka, G

2016-11-01

Prognosis of patients with head and neck squamous cell carcinoma (HNSCC) is still poor. Novel therapeutic approaches are of great interest to improve the effects of radiochemotherapy. We evaluated the effects of tyrosine kinase inhibitor neratinib on HNSCC cell lines CAL27, SCC25 and FaDu as a single agent and in combination with irradiation and chemotherapy. Effects of neratinib were evaluated in HNSCC cell lines CAL27, SCC25 and FaDu. Effect on cell viability of neratinib and combination with cisplatin and irradiation was measured using CCK-8 assays and clonogenic assays. Western blot analysis was performed to distinguish the effect on epithelial growth factor receptor and HER2 expression. Apoptosis was evaluated by flow cytometry analysis. Growth inhibition was achieved in all cell lines, whereas combination of cisplatin and neratinib showed greater inhibition than each agent alone. Apoptosis was induced in all cell lines. Combination of neratinib with irradiation or cisplatin showed significantly increased apoptosis. In clonogenic assays, significant growth inhibition was observed in all investigated cell lines. Neratinib, as a single agent or in combination with chemo-irradiation, may be a promising treatment option for patients with head and neck cancer. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Acacia catechu ethanolic bark extract induces apoptosis in human oral squamous carcinoma cells.

PubMed

Lakshmi, Thangavelu; Ezhilarasan, Devaraj; Vijayaragavan, Rajagopal; Bhullar, Sukhwinder Kaur; Rajendran, Ramasamy

2017-01-01

Oral cancer is in approximately 30% of all cancers in India. This study was conducted to evaluate the cytotoxic activity of ethanolic extract of Acacia catechu bark (ACB) against human squamous cell carcinoma cell line-25 (SCC-25). Cytotoxic effect of ACB extract was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium Bromide assay. A. catechu extract was treated SCC-25 cells with 25 and 50 μg/mL for 24 h. Apoptosis markers such as caspases-8 and 9, bcl-2, bax, and cytochrome c (Cyt-c) were done by RT-PCR. Morphological changes of ACB treated cells were evaluated using acridine orange/ethidium bromide (AO/EB) dual staining. Nuclear morphology and DNA fragmentation were evaluated using propidium iodide (PI) staining. Further, cell cycle analysis was performed using flow cytometry. A. catechu treatment caused cytotoxicity in SCC-25 cells with an IC 50 of 52.09 μg/mL. Apoptotic marker gene expressions were significantly increased on ACB treatment. Staining with AO/EB and PI shows membrane blebbing and nuclear membrane distortion, respectively, and it confirms the apoptosis induction in SCC-25 cells. These results suggest that ACB extract can be used as a modulating agent in oral squamous cell carcinoma.

Differential immunohistochemical expression profiles of perlecan-binding growth factors in epithelial dysplasia, carcinoma in situ, and squamous cell carcinoma of the oral mucosa.

PubMed

Hasegawa, Mayumi; Cheng, Jun; Maruyama, Satoshi; Yamazaki, Manabu; Abé, Tatsuya; Babkair, Hamzah; Saito, Chikara; Saku, Takashi

2016-05-01

The intercellular deposit of perlecan, a basement-membrane type heparan sulfate proteoglycan, is considered to function as a growth factor reservoir and is enhanced in oral epithelial dysplasia and carcinoma in situ (CIS). However, it remains unknown which types of growth factors function in these perlecan-enriched epithelial conditions. The aim of this study was to determine immunohistochemically which growth factors were associated with perlecan in normal oral epithelia and in different epithelial lesions from dysplasia and CIS to squamous cell carcinoma (SCC). Eighty-one surgical tissue specimens of oral SCC containing different precancerous stages, along with ten of normal mucosa, were examined by immunohistochemistry for growth factors. In normal epithelia, perlecan and growth factors were not definitely expressed. In epithelial dysplasia, VEGF, SHH, KGF, Flt-1, and Flk-1were localized in the lower half of rete ridges (in concordance with perlecan, 33-100%), in which Ki-67 positive cells were densely packed. In CIS, perlecan and those growth factors/receptors were more strongly expressed in the cell proliferating zone (63-100%). In SCC, perlecan and KGF disappeared from carcinoma cells but emerged in the stromal space (65-100%), while VEGF, SHH, and VEGF receptors remained positive in SCC cells (0%). Immunofluorescence showed that the four growth factors were shown to be produced by three oral SCC cell lines and that their signals were partially overlapped with perlecan signals. The results indicate that perlecan and its binding growth factors are differentially expressed and function in specific manners before (dysplasia/CIS) and after (SCC) invasion of dysplasia/carcinoma cells. Copyright © 2016 Elsevier GmbH. All rights reserved.

Berberine suppresses in vitro migration and invasion of human SCC-4 tongue squamous cancer cells through the inhibitions of FAK, IKK, NF-kappaB, u-PA and MMP-2 and -9.

PubMed

Ho, Yung-Tsuan; Yang, Jai-Sing; Li, Tsai-Chung; Lin, Jen-Jyh; Lin, Jaung-Geng; Lai, Kuang-Chi; Ma, Chia-Yu; Wood, W Gibson; Chung, Jing-Gung

2009-07-08

There is increasing evidence that urokinase-type plasminogen activator (u-PA) and matrix metalloproteinases (MMPs) play an important role in cancer metastasis and angiogenesis. Inhibition of u-PA and MMPs could suppress migration and invasion of cancer cells. Berberine, one of the main constituents of the plant Rhizoma coptidis, is a type of isoquinoline alkaloid, reported to have anti-cancer effects in different human cancer cell lines. There is however, no available information on effects of berberine on migration and invasion of human tongue cancer cells. Here, we report that berberine inhibited migration and invasion of human SCC-4 tongue squamous carcinoma cells. This action was mediated by the p-JNK, p-ERK, p-p38, IkappaK and NF-kappaB signaling pathways resulting in inhibition of MMP-2 and -9 in human SCC-4 tongue squamous carcinoma cells. Our Western blowing analysis also showed that berberine inhibited the levels of urokinase-plasminogen activator (u-PA). These results suggest that berberine down-regulates u-PA, MMP-2 and -9 expressions in SCC-4 cells through the FAK, IKK and NF-kappaB mediated pathways and a novel function of berberine is to inhibit the invasive capacity of malignant cells.

Fisetin-induced apoptosis of human oral cancer SCC-4 cells through reactive oxygen species production, endoplasmic reticulum stress, caspase-, and mitochondria-dependent signaling pathways.

PubMed

Su, Chen-Hsuan; Kuo, Chao-Lin; Lu, Kung-Wen; Yu, Fu-Shun; Ma, Yi-Shih; Yang, Jiun-Long; Chu, Yung-Lin; Chueh, Fu-Shin; Liu, Kuo-Ching; Chung, Jing-Gung

2017-06-01

Oral cancer is one of the cancer-related diseases in human populations and its incidence rates are rising worldwide. Fisetin, a flavonoid from natural products, has been shown to exhibit anticancer activities in many human cancer cell lines but the molecular mechanism of fisetin-induced apoptosis in human oral cancer cells is still unclear; thus, in this study, we investigated fisetin-induced cell death and associated signal pathways on human oral cancer SCC-4 cells in vitro. We examined cell morphological changes, total viable cells, and cell cycle distribution by phase contrast microscopy and flow cytometry assays. Reactive oxygen species (ROS), Ca 2+ , mitochondria membrane potential (ΔΨ m ), and caspase-8, -9, and -3 activities were also measured by flow cytometer. Results indicate that fisetin induced cell death through the cell morphological changes, caused G2/M phase arrest, induction of apoptosis, promoted ROS and Ca 2+ production, and decreased the level of ΔΨ m and increased caspase-3, -8, and -9 activities in SCC-4 cells. DAPI staining and DNA gel electrophoresis were also used to confirm fisetin-induced cell apoptosis in SCC-4 cells. Western blotting also found out that Fisetin increased the proapoptotic proteins such as Bax and Bid and decreased the antiapoptotic proteins such as Bcl-2. Furthermore, results also showed that Fisetin increased the cytochrome c, AIF, and Endo G release from mitochondria in SCC-4 cells. We also used ATF-6α, ATF-6β, GADD153, and GRP78 which indicated that fisetin induced cell death through ER stress. Based on those observations, we suggest that fisetin induced cell apoptosis through ER stress, mitochondria-, and caspase-dependent pathways. © 2017 Wiley Periodicals, Inc.

Somatically Acquired LINE-1 Insertions in Normal Esophagus Undergo Clonal Expansion in Esophageal Squamous Cell Carcinoma.

PubMed

Doucet-O'Hare, Tara T; Sharma, Reema; Rodić, Nemanja; Anders, Robert A; Burns, Kathleen H; Kazazian, Haig H

2016-09-01

Squamous cell carcinoma of the esophagus (SCC) is the most common form of esophageal cancer in the world and is typically diagnosed at an advanced stage when successful treatment is challenging. Understanding the mutational profile of this cancer may identify new treatment strategies. Because somatic retrotransposition has been shown in tumors of the gastrointestinal system, we focused on LINE-1 (L1) mobilization as a source of genetic instability in this cancer. We hypothesized that retrotransposition is ongoing in SCC patients. The expression of L1 encoded proteins is necessary for retrotransposition to occur; therefore, we evaluated the expression of L1 open reading frame 1 protein (ORF1p). Using immunohistochemistry, we detected ORF1p expression in all four SCC cases evaluated. Using L1-seq, we identified and validated 74 somatic insertions in eight tumors of the nine evaluated. Of these, 12 insertions appeared to be somatic, not genetically inherited, and sub-clonal (i.e., present in less than one copy per genome equivalent) in the adjacent normal esophagus (NE), while clonal in the tumor. Our results indicate that L1 retrotransposition is active in SCC of the esophagus and that insertion events are present in histologically NE that expands clonally in the subsequent tumor. © 2016 WILEY PERIODICALS, INC.

Field validation of protocols developed to evaluate in-line mastitis detection systems.

PubMed

Kamphuis, C; Dela Rue, B T; Eastwood, C R

2016-02-01

This paper reports on a field validation of previously developed protocols for evaluating the performance of in-line mastitis-detection systems. The protocols outlined 2 requirements of these systems: (1) to detect cows with clinical mastitis (CM) promptly and accurately to enable timely and appropriate treatment and (2) to identify cows with high somatic cell count (SCC) to manage bulk milk SCC levels. Gold standard measures, evaluation tests, performance measures, and performance targets were proposed. The current study validated the protocols on commercial dairy farms with automated in-line mastitis-detection systems using both electrical conductivity (EC) and SCC sensor systems that both monitor at whole-udder level. The protocol for requirement 1 was applied on 3 commercial farms. For requirement 2, the protocol was applied on 6 farms; 3 of them had low bulk milk SCC (128×10(3) cells/mL) and were the same farms as used for field evaluation of requirement 1. Three farms with high bulk milk SCC (270×10(3) cells/mL) were additionally enrolled. The field evaluation methodology and results were presented at a workshop including representation from 7 international suppliers of in-line mastitis-detection systems. Feedback was sought on the acceptance of standardized performance evaluation protocols and recommended refinements to the protocols. Although the methodology for requirement 1 was relatively labor intensive and required organizational skills over an extended period, no major issues were encountered during the field validation of both protocols. The validation, thus, proved the protocols to be practical. Also, no changes to the data collection process were recommended by the technology supplier representatives. However, 4 recommendations were made to refine the protocols: inclusion of an additional analysis that ignores small (low-density) clot observations in the definition of CM, extension of the time window from 4 to 5 milkings for timely alerts for CM, setting a maximum number of 10 milkings for the time window to detect a CM episode, and presentation of sensitivity for a larger range of false alerts per 1,000 milkings replacing minimum performance targets. The recommended refinements are discussed with suggested changes to the original protocols. The information presented is intended to inform further debate toward achieving international agreement on standard protocols to evaluate performance of in-line mastitis-detection systems. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

FGFR signaling regulates resistance of head and neck cancer stem cells to cisplatin.

PubMed

McDermott, Sarah C; Rodriguez-Ramirez, Christie; McDermott, Sean P; Wicha, Max S; Nör, Jacques E

2018-05-18

Patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) have poor prognosis with less than 1-year median survival. Platinum-based chemotherapy remains the first-line treatment for HNSCC. The cancer stem cell (CSC) hypothesis postulates that tumors are maintained by a self-renewing CSC population that is also capable of differentiating into non-self renewing cell populations that constitute the bulk of the tumor. A small population of CSC exists within HNSCC that are relatively resistant to chemotherapy and clinically predicted to contribute to tumor recurrence. These head and neck CSCs (HNCSC) are identified by high cell-surface expression of CD44 and high intracellular activity of aldehyde dehydrogenase (ALDH) and termed ALDH high CD44 high . Here, we performed microarray analysis in two HNSCC cell lines (UM-SCC-1, UM-SCC-22B) to investigate molecular pathways active in untreated and cisplatin-resistant ALDH high CD44 high cells. Gene set enrichment analysis and iPathway analysis identified signaling pathways with major implications to the pathobiology of cancer (e.g. TNFα, IFN, IL6/STAT, NF-κB) that are enriched in cisplatin-resistant ALDH high CD44 high cells, when compared to control cells. FGF2 was also enriched in cisplatin-resistant ALDH high CD44 high , which was confirmed by ELISA analysis. Inhibition of FGF signaling using BGJ398, a pan-FGF receptor (FGFR) small-molecule inhibitor, decreased ALDH high CD44 high alone in UM-SCC-1 and preferentially targeted cisplatin-resistant ALDH high CD44 high cells in UM-SCC-22B. These findings suggest that FGFR signaling might play an important role in the resistance of head and neck CSC to cisplatin. Collectively, this work suggests that some head and neck cancer patients might benefit from the combination of cisplatin and a FGFR inhibitor.

pSTAT3 Levels Have Divergent Expression Patterns and Associations with Survival in Squamous Cell Carcinoma and Adenocarcinoma of the Oesophagus.

PubMed

O' Sullivan, Katie E; Michielsen, Adriana J; O' Regan, Esther; Cathcart, Mary C; Moore, Gillian; Breen, Eamon; Segurado, Ricardo; Reynolds, John V; Lysaght, Joanne; O' Sullivan, Jacintha

2018-06-10

Signal transducers and activator of transcription (STAT)-3 is activated in cancers, where it promotes growth, inflammation, angiogenesis, and inhibits apoptosis. Tissue microarrays were generated using tissues from 154 patients, with oesophageal adenocarcinoma (OAC) ( n = 116) or squamous cell carcinoma (SCC) ( n = 38) tumours. The tissues were stained for pSTAT3 and IL-6R using immunohistochemistry. The OE33 (OAC) and OE21 (SCC) cell lines were treated with the STAT3 inhibitor, STATTIC. The Univariate cox regression analysis revealed that a positive pSTAT3 in SCC was adversely associated with survival (Hazard ratio (HR) 6.382, 95% CI 1.266⁻32.184), while a protective effect was demonstrated with the higher pSTAT3 levels in OAC epithelium (HR 0.74, 95% CI 0.574⁻0.953). The IL-6R intensity levels were higher in the SCC tumours compared with the OAC tumours for the core and leading edge tumour tissue. The pSTAT3 levels correlated positively with the IL-6R levels in both the OAC and SCC. The treatment of OE21 and OE33 cells with the STAT3 inhibitor STATTIC in vitro resulted in decreased survival, proliferation, migration, and increased apoptosis. The pSTAT3 expression was associated with adverse survival in SCC, but not in the OAC patients. The inhibition of STAT3 in both of the tumour subtypes resulted in alterations in the survival, proliferation, migration, and apoptosis, suggesting a potential role for therapeutically targeting STAT3.

In vitro Antiproliferative Effect of Earthworm Coelomic Fluid of Eudrilus Eugeniae, Eisenia Foetida, and Perionyx Excavatus on Squamous Cell Carcinoma-9 Cell Line: A Pilot Study.

PubMed

Augustine, Dominic; Rao, Roopa S; Anbu, Jayaraman; Chidambara Murthy, K N

2017-12-01

The earthworm coelomic fluid (ECF) has shown proven antiproliferative effect against breast, liver, gastrointestinal, and brain cancer, but it is least explored in oral cancer. The present in vitro study is an attempt to investigate the antiproliferative activity of ECF on oral cancer cell line squamous cell carcinoma (SCC)-9. ECF was collected from the species Eudrilus eugeniae (EE), Eisenia foetida (EF), and Perionyx excavatus (PE) stored at -80°C. Percentage inhibition of ECF on squamous cell carcinoma-9 cells in vitro was recorded at 24 h. Protein estimation was done using Bradford protein assay validated by the biuret method. Cytotoxicity was tested at 2.5, 5, 10, 20, 40, and 80 μg/ml concentrations by 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay in SCC-9 cells in vitro . GraphPad Prism 7.0 software was used to calculate the inhibitory concentration (IC 50 ). Chi-square test was used to analyze the difference between samples. The test samples EE, EF, and PE inhibited the growth of SCC-9 cells significantly in a dose-dependent manner, and the IC 50 values were found to be 4.6, 44.69, and 5.27 μg/ml, respectively. The antiproliferative effect was found to be variable among the three earthworm species with EE showing the most promising effect followed by PE and EF. Establishing the antiproliferative effect of ECF on oral cancer cells could be an initial step toward drug development and future anticancer research. The preliminary investigation has shown that ECF has a promising antiproliferative effect on oral cancer cells in vitro . The present pilot study evaluated the in vitro antiproliferative effect of earthworm coelomic fluid (ECF) of Eudrilus eugeniae (EE), Eisenia foetida (EF), and Perionyx excavatus (PE) on squamous cell carcinoma-9 cell line. The ECF inhibitory activity was promising at inhibitory concentration values of 4.6, 44.69, and 5.27 μg/ml, respectively. Further studies pertaining to antiproliferative mechanism of EE, EF, and PE have been planned. Abbreviations Used: ECF: Earthworm coelomic fluid, EE: Eudrilus eugeniae , EF: Eisenia foetida , PE: Perionyx excavatus , MTT: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, SCC: Squamous cell carcinoma, BSA: Bovine serum albumin, PBS: Phosphored buffered saline, ATCC: American Type Culture Collection.

MicroRNA and protein profiles in invasive versus non-invasive oral tongue squamous cell carcinoma cells in vitro

DOE Office of Scientific and Technical Information (OSTI.GOV)

Korvala, Johanna, E-mail: johanna.korvala@oulu.fi; Jee, Kowan; Department of Pathology, Haartman Institute, University of Helsinki, Helsinki

Complex molecular pathways regulate cancer invasion. This study overviewed proteins and microRNAs (miRNAs) involved in oral tongue squamous cell carcinoma (OTSCC) invasion. The human highly aggressive OTSCC cell line HSC-3 was examined in a 3D organotypic human leiomyoma model. Non-invasive and invasive cells were laser-captured and protein expression was analyzed using mass spectrometry-based proteomics and miRNA expression by microarray. In functional studies the 3D invasion assay was replicated after silencing candidate miRNAs, miR-498 and miR-940, in invasive OTSCC cell lines (HSC-3 and SCC-15). Cell migration, proliferation and viability were also studied in the silenced cells. In HSC-3 cells, 67 proteinsmore » and 53 miRNAs showed significant fold-changes between non-invasive vs. invasive cells. Pathway enrichment analyses allocated “Focal adhesion” and “ECM-receptor interaction” as most important for invasion. Significantly, in HSC-3 cells, miR-498 silencing decreased the invasion area and miR-940 silencing reduced invasion area and depth. Viability, proliferation and migration weren’t significantly affected. In SCC-15 cells, down-regulation of miR-498 significantly reduced invasion and migration. This study shows HSC-3 specific miRNA and protein expression in invasion, and suggests that miR-498 and miR-940 affect invasion in vitro, the process being more influenced by mir-940 silencing in aggressive HSC-3 cells than in the less invasive SCC-15.« less

Identification and Characterization of Cells with Cancer Stem Cell Properties in Human Primary Lung Cancer Cell Lines

PubMed Central

Suo, Zhenhe; Munthe, Else; Solberg, Steinar; Ma, Liwei; Wang, Mengyu; Westerdaal, Nomdo Anton Christiaan; Kvalheim, Gunnar; Gaudernack, Gustav

2013-01-01

Lung cancer (LC) with its different subtypes is generally known as a therapy resistant cancer with the highest morbidity rate worldwide. Therapy resistance of a tumor is thought to be related to cancer stem cells (CSCs) within the tumors. There have been indications that the lung cancer is propagated and maintained by a small population of CSCs. To study this question we established a panel of 15 primary lung cancer cell lines (PLCCLs) from 20 fresh primary tumors using a robust serum-free culture system. We subsequently focused on identification of lung CSCs by studying these cell lines derived from 4 representative lung cancer subtypes such as small cell lung cancer (SCLC), large cell carcinoma (LCC), squamous cell carcinoma (SCC) and adenocarcinoma (AC). We identified a small population of cells strongly positive for CD44 (CD44high) and a main population which was either weakly positive or negative for CD44 (CD44low/−). Co-expression of CD90 further narrowed down the putative stem cell population in PLCCLs from SCLC and LCC as spheroid-forming cells were mainly found within the CD44highCD90+ sub-population. Moreover, these CD44highCD90+ cells revealed mesenchymal morphology, increased expression of mesenchymal markers N-Cadherin and Vimentin, increased mRNA levels of the embryonic stem cell related genes Nanog and Oct4 and increased resistance to irradiation compared to other sub-populations studied, suggesting the CD44highCD90+ population a good candidate for the lung CSCs. Both CD44highCD90+ and CD44highCD90− cells in the PLCCL derived from SCC formed spheroids, whereas the CD44low/− cells were lacking this potential. These results indicate that CD44highCD90+ sub-population may represent CSCs in SCLC and LCC, whereas in SCC lung cancer subtype, CSC potentials were found within the CD44high sub-population. PMID:23469181

Epigenetic repression of HOXB cluster in oral cancer cell lines.

PubMed

Xavier, Flávia Caló Aquino; Destro, Maria Fernanda de Souza Setubal; Duarte, Carina Magalhães Esteves; Nunes, Fabio Daumas

2014-08-01

Aberrant DNA methylation is a fundamental transcriptional control mechanism in carcinogenesis. The expression of homeobox genes is usually controlled by an epigenetic mechanism, such as the methylation of CpG islands in the promoter region. The aim of this study was to describe the differential methylation pattern of HOX genes in oral squamous cell carcinoma (OSCC) cell lines and transcript status in a group of hypermethylated and hypomethylated genes. Quantitative analysis of DNA methylation was performed on two OSCC cell lines (SCC4 and SCC9) using a method denominated Human Homeobox Genes EpiTect Methyl qPCR Arrays, which allowed fast, precise methylation detection of 24 HOX specific genes without bisulfite conversion. Methylation greater than 50% was detected in HOXA11, HOXA6, HOXA7, HOXA9, HOXB1, HOXB2, HOXB3, HOXB4, HOXB5, HOXB6, HOXC8 and HOXD10. Both cell lines demonstrated similar hypermethylation status for eight HOX genes. A similar pattern of promoter hypermethylation and hypomethylation was demonstrated for the HOXB cluster and HOXA cluster, respectively. Moreover, the hypermethylation profile of the HOXB cluster, especially HOXB4, was correlated with decreased transcript expression, which was restored following treatment with 5-aza-2'-deoxycytidine. The homeobox methylation profile in OSCC cell lines is consistent with an epigenetic biomarker. Copyright © 2014 Elsevier Ltd. All rights reserved.

CXCR6 expression in non-small cell lung carcinoma supports metastatic process via modulating metalloproteinases.

PubMed

Mir, Hina; Singh, Rajesh; Kloecker, Goetz H; Lillard, James W; Singh, Shailesh

2015-04-30

Lung cancer (LuCa) is the leading cause of cancer-related deaths worldwide regardless of the gender. High mortality associated with LuCa is due to metastasis, molecular mechanisms of which are yet to be defined. Here, we present evidence that chemokine receptor CXCR6 and its only natural ligand, CXCL16, are significantly expressed by non-small cell lung cancer (NSCLC) and are involved in the pathobiology of LuCa. CXCR6 expression was significantly higher in two subtypes of NSCLC (adenocarcinomas-ACs and squamous cell carcinoma-SCCs) as compared to non-neoplastic tissue. Additionally, serum CXCL16 was significantly elevated in LuCa cases as compared to healthy controls. Similar to CXCR6 tissue expression, serum level of CXCL16 in AC patients was significantly higher than SCC patients. Biological significance of this axis was validated using SCC and AC cell lines. Expression of CXCR6 was higher in AC cells, which also showed higher migratory and invasive potential than SCC. Differences in migratory and invasive potential between AC and SCC were due to differential expression of metalloproteinases following CXCL16 stimulation. Hence, our findings suggest clinical and biological significance of CXCR6/CXCL16 axis in LuCa, which could be used as potential prognostic marker and therapeutic target.

CXCR6 expression in non-small cell lung carcinoma supports metastatic process via modulating metalloproteinases

PubMed Central

Mir, Hina; Singh, Rajesh; Kloecker, Goetz H.; Lillard, James W.; Singh, Shailesh

2015-01-01

Lung cancer (LuCa) is the leading cause of cancer-related deaths worldwide regardless of the gender. High mortality associated with LuCa is due to metastasis, molecular mechanisms of which are yet to be defined. Here, we present evidence that chemokine receptor CXCR6 and its only natural ligand, CXCL16, are significantly expressed by non-small cell lung cancer (NSCLC) and are involved in the pathobiology of LuCa. CXCR6 expression was significantly higher in two subtypes of NSCLC (adenocarcinomas-ACs and squamous cell carcinoma-SCCs) as compared to non-neoplastic tissue. Additionally, serum CXCL16 was significantly elevated in LuCa cases as compared to healthy controls. Similar to CXCR6 tissue expression, serum level of CXCL16 in AC patients was significantly higher than SCC patients. Biological significance of this axis was validated using SCC and AC cell lines. Expression of CXCR6 was higher in AC cells, which also showed higher migratory and invasive potential than SCC. Differences in migratory and invasive potential between AC and SCC were due to differential expression of metalloproteinases following CXCL16 stimulation. Hence, our findings suggest clinical and biological significance of CXCR6/CXCL16 axis in LuCa, which could be used as potential prognostic marker and therapeutic target. PMID:25888629

Multiple cells express interleukin 17 in oral squamous cell carcinoma.

PubMed

Avadhani, Avadhoot V; Parachuru, Venkata P B; Milne, Trudy; Seymour, Gregory J; Rich, Alison M

2017-01-01

Interleukin (IL)-17 is a pro-inflammatory cytokine with pro- and antitumour effects. The aim of this study was to investigate the presence and potential sources of IL-17 in oral squamous cell carcinoma (OSCC). Immunohistochemistry was used to label and compare IL-17 + cells in the tissue sections of OSCC and inflammatory controls (IC), n = 14 for both. In OSCC, the comparison was made between the number of IL-17 + cells in the tumoral islands (TI), tumour-stroma interface (TS) and more distant stroma (DS). Cells expressing IL-17 were identified using double-labelling immunofluorescence and examined using laser scanning microscopy. The production of IL-17 from tumour cells was determined in the culture supernatants of OSCC cell lines, SCC4, SCC15 and SCC25, using sandwich ELISA. Significantly more IL-17 + cells were observed in OSCC compared with IC (Mann-Whitney, P < 0.0001). In OSCC, the numbers of IL-17 + cells were not significantly different in three compartments, TI, TS and DS (one-way ANOVA, P > 0.05). However, the TI had significantly fewer IL-17 + cells than the combined stroma (both TS and DS together, Mann-Whitney, P < 0.01). Laser scanning microscopy revealed helper T cells, cytotoxic T cells, macrophages and mast cells co-expressed IL-17. ELISA experiments did not detect IL-17 in the supernatants of OSCC cell lines. Although the tumour cells themselves did not express IL-17, a range of cell types did, suggesting multiple cellular sources for IL-17 in OSCC. The spatial distribution of IL-17 + cells suggests specific interactions with cells within the tumour microenvironment, implying that IL-17 + cells are likely to play a role in the pathogenesis of OSCC. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Hepatocyte growth factor activator inhibitor type-2 (HAI-2)/SPINT2 contributes to invasive growth of oral squamous cell carcinoma cells.

PubMed

Yamamoto, Koji; Kawaguchi, Makiko; Shimomura, Takeshi; Izumi, Aya; Konari, Kazuomi; Honda, Arata; Lin, Chen-Yong; Johnson, Michael D; Yamashita, Yoshihiro; Fukushima, Tsuyoshi; Kataoka, Hiroaki

2018-02-20

Hepatocyte growth factor activator inhibitor (HAI)-1/ SPINT1 and HAI-2/ SPINT2 are membrane-anchored protease inhibitors having homologous Kunitz-type inhibitor domains. They regulate membrane-anchored serine proteases, such as matriptase and prostasin. Whereas HAI-1 suppresses the neoplastic progression of keratinocytes to invasive squamous cell carcinoma (SCC) through matriptase inhibition, the role of HAI-2 in keratinocytes is poorly understood. In vitro homozygous knockout of the SPINT2 gene suppressed the proliferation of two oral SCC (OSCC) lines (SAS and HSC3) but not the growth of a non-tumorigenic keratinocyte line (HaCaT). Reversion of HAI-2 abrogated the growth suppression. Matrigel invasion of both OSCC lines was also suppressed by the loss of HAI-2. The levels of prostasin protein were markedly increased in HAI-2-deficient cells, and knockdown of prostasin alleviated the HAI-2 loss-induced suppression of OSCC cell invasion. Therefore, HAI-2 has a pro-invasive role in OSCC cells through suppression of prostasin. In surgically resected OSCC tissues, HAI-2 immunoreactivity increased along with neoplastic progression, showing intense immunoreactivities in invasive OSCC cells. In summary, HAI-2 is required for invasive growth of OSCC cells and may contribute to OSCC progression.

Fisetin suppresses malignant proliferation in human oral squamous cell carcinoma through inhibition of Met/Src signaling pathways.

PubMed

Li, Yan-Shu; Qin, Xing-Jun; Dai, Wei

2017-01-01

Fisetin (3,7,3',4'-tetrahydroxyflavone) is a dietary flavonoid and has been indicated as a novel anti-cancer agent in several types of cancer cells. However, the mechanisms underlying the effect of fisetin in human oral squamous cell carcinoma (OSCC) remain unclear. Here, we report that fisetin significantly inhibits tumor cell proliferation and induces apoptosis in OSCC (UM-SCC-23 and Tca-8113) cancer cell lines. Further analysis demonstrates that fisetin also inhibits Met/Src signaling pathways using the PathScan ® receptor tyrosine kinases (RTK) Signaling Antibody Array Kit. Fisetin resulted in decreased basal expression of Met and Src protein in UM-SCC-23 cancer cell lines, which validated by western blot. A student's t -test (two-tailed) was used to compare differences between groups. Furthermore, fisetin significantly inhibited the expression of a disintegrin and metalloproteinase 9 (ADAM9) protein in OSCC cells. Taken together, these results provide novel insights into the mechanism of fisetin and suggest potential therapeutic strategies for human OSCC by blocking the Met/Src signaling pathways.

Osteoactivin regulates head and neck squamous cell carcinoma invasion by modulating matrix metalloproteases.

PubMed

Arosarena, Oneida A; Barr, Eric W; Thorpe, Ryan; Yankey, Hilary; Tarr, Joseph T; Safadi, Fayez F

2018-01-01

Nearly 60% of patients with head and neck squamous cell carcinoma (HNSCC) die of metastases or locoregional recurrence. Metastasis is mediated by cancer cell migration and invasion, which are in part dependent on extracellular matrix degradation by matrix metalloproteinases. Osteoactivin (OA) overexpression plays a role in metastases in several malignancies, and has been shown to upregulate matrix metalloproteinase (MMP) expression and activity. To determine how OA modulates MMP expression and activity in HNSCC, and to investigate OA effects on cell invasion, we assessed effects of OA treatment on MMP mRNA and protein expression, as well as gelatinase and caseinolytic activity in HNSCC cell lines. We assessed the effects of OA gene silencing on MMP expression, gelatinase and caseinolytic activity, and cell invasion. OA treatment had differential effects on MMP mRNA expression. OA treatment upregulated MMP-10 expression in UMSCC14a (p = 0.0431) and SCC15 (p < 0.0001) cells, but decreased MMP-9 expression in UMSCC14a cells (p = 0.0002). OA gene silencing decreased MMP-10 expression in UMSCC12 cells (p = 0.0001), and MMP-3 (p = 0.0005) and -9 (p = 0.0036) expression in SCC25 cells. In SCC15 and SCC25 cells, OA treatment increased MMP-2 (p = 0.0408) and MMP-9 gelatinase activity (p < 0.0001), respectively. OA depletion decreased MMP-2 (p = 0.0023) and -9 (p < 0.0001) activity in SCC25 cells. OA treatment increased 70 kDa caseinolytic activity in UMSCC12 cells consistent with tissue type plasminogen activator (p = 0.0078). OA depletion decreased invasive capacity of UMSCC12 cells (p < 0.0001). OA's effects on MMP expression in HNSCC are variable, and may promote cancer cell invasion. © 2017 Wiley Periodicals, Inc.

Heat shock protein 90 (HSP90) is overexpressed in p16-negative oropharyngeal squamous cell carcinoma, and its inhibition in vitro potentiates the effects of chemoradiation.

PubMed

Patel, Kirtesh; Wen, Jing; Magliocca, Kelly; Muller, Susan; Liu, Yuan; Chen, Zhuo Georgia; Saba, Nabil; Diaz, Roberto

2014-11-01

Cisplatin and radiation therapy remain the current standard for treating locally advanced SCCHN. Novel treatment approaches are needed, especially in patients with human papilloma virus (HPV)-negative disease who have worse outcomes despite multimodality therapy. Using our institutional review board approved database, we obtained twenty oropharyngeal squamous cell carcinoma (SCC) tissue samples: ten p16 positive, ten p16-negative. Because p16 expression is strongly associated with HPV positivity in oropharyngeal SCC, p16 status was used as a marker of HPV. We subsequently analyzed, via immunohistochemistry, heat shock protein 90 (HSP90) protein levels. Using HPV-positive and HPV-negative SCC cell lines, we compared baseline HSP90 expression levels and the effect of the HSP90 inhibitor ganetespib on viability and apoptosis. Clonogenic survival of HPV-negative cells treated with ganetespib, radiation therapy, and/or cisplatin was then investigated. We characterize the effects of ganetespib on proteins that are thought to drive DNA damage resistance in HPV-negative cells. HSP90 expression was significantly higher in p16-negative compared with p16-positive samples (p = 0.016) and in HPV-negative cell lines compared with positive cells. Ganetespib increased cytotoxicity and induced apoptosis in HPV-negative more than positive cells. Adding ganetespib to cisplatin and/or radiation therapy in HPV-negative cells further decreased clonogenic survival. Finally, ganetespib downregulated expressions of EGFR, ERK, AKT, p53, and HIF-1α. Ganetespib inhibited HPV-negative SCCHN viability and potentiated cell kill when combined with cisplatin or radiation therapy in vitro. With HSP90 expression higher in HPV-negative cells and in p16-negative patients, further exploration of the clinical activity of HSP90 inhibitors in SCCHN is warranted.

Methyl-donor depletion of head and neck cancer cells in vitro establishes a less aggressive tumour cell phenotype.

PubMed

Hearnden, Vanessa; Powers, Hilary J; Elmogassabi, Abeir; Lowe, Rosanna; Murdoch, Craig

2018-06-01

DNA methylation plays a fundamental role in the epigenetic control of carcinogenesis and is, in part, influenced by the availability of methyl donors obtained from the diet. In this study, we developed an in-vitro model to investigate whether methyl donor depletion affects the phenotype and gene expression in head and neck squamous cell carcinoma (HNSCC) cells. HNSCC cell lines (UD-SCC2 and UPCI-SCC72) were cultured in medium deficient in methionine, folate, and choline or methyl donor complete medium. Cell doubling-time, proliferation, migration, and apoptosis were analysed. The effects of methyl donor depletion on enzymes controlling DNA methylation and the pro-apoptotic factors death-associated protein kinase-1 (DAPK1) and p53 upregulated modulator of apoptosis (PUMA) were examined by quantitative-PCR or immunoblotting. HNSCC cells cultured in methyl donor deplete conditions showed significantly increased cell doubling times, reduced cell proliferation, impaired cell migration, and a dose-dependent increase in apoptosis when compared to cells cultured in complete medium. Methyl donor depletion significantly increased the gene expression of DNMT3a and TET-1, an effect that was reversed upon methyl donor repletion in UD-SCC2 cells. In addition, expression of DAPK1 and PUMA was increased in UD-SCC2 cells cultured in methyl donor deplete compared to complete medium, possibly explaining the observed increase in apoptosis in these cells. Taken together, these data show that depleting HNSCC cells of methyl donors reduces the growth and mobility of HNSCC cells, while increasing rates of apoptosis, suggesting that a methyl donor depleted diet may significantly affect the growth of established HNSCC.

Genetic analysis for mastitis resistance and milk somatic cell score in French Lacaune dairy sheep

PubMed Central

Barillet, Francis; Rupp, Rachel; Mignon-Grasteau, Sandrine; Astruc, Jean-Michel; Jacquin, Michèle

2001-01-01

Genetic analysis for mastitis resistance was studied from two data sets. Firstly, risk factors for different mastitis traits, i.e. culling due to clinical or chronic mastitis and subclinical mastitis predicted from somatic cell count (SCC), were explored using data from 957 first lactation Lacaune ewes of an experimental INRA flock composed of two divergent lines for milk yield. Secondly, genetic parameters for SCC were estimated from 5 272 first lactation Lacaune ewes recorded among 38 flocks, using an animal model. In the experimental flock, the frequency of culling due to clinical mastitis (5%) was lower than that of subclinical mastitis (10%) predicted from SCC. Predicted subclinical mastitis was unfavourably associated with the milk yield level. Such an antagonism was not detected for clinical mastitis, which could result, to some extent, from its low frequency or from the limited amount of data. In practice, however, selection for mastitis resistance could be limited in a first approach to selection against subclinical mastitis using SCC. The heritability estimate of SCC was 0.15 for the lactation mean trait and varied from 0.04 to 0.12 from the first to the fifth test-day. The genetic correlation between lactation SCC and milk yield was slightly positive (0.15) but showed a strong evolution during lactation, i.e. from favourable (-0.48) to antagonistic (0.27). On a lactation basis, our results suggest that selection for mastitis resistance based on SCC is feasible. Patterns for genetic parameters within first lactation, however, require further confirmation and investigation. PMID:11559483

Erbb2 up-regulation of ADAM12 expression accelerates skin cancer progression.

PubMed

Rao, Velidi H; Vogel, Kristen; Yanagida, Jodi K; Marwaha, Nitin; Kandel, Amrit; Trempus, Carol; Repertinger, Susan K; Hansen, Laura A

2015-10-01

Solar ultraviolet (UV) radiation can cause severe damage to the skin and is the primary cause of most skin cancer. UV radiation causes DNA damage leading to mutations and also activates the Erbb2/HER2 receptor through indirect mechanisms involving reactive oxygen species. We hypothesized that Erbb2 activation accelerates the malignant progression of UV-induced skin cancer. Following the induction of benign squamous papillomas by UV exposure of v-ras(Ha) transgenic Tg.AC mice, mice were treated topically with the Erbb2 inhibitor AG825 and tumor progression monitored. AG825 treatment reduced tumor volume, increased tumor regression, and delayed the development of malignant squamous cell carcinoma (SCC). Progression to malignancy was associated with increased Erbb2 and ADAM12 (A Disintegin And Metalloproteinase 12) transcripts and protein, while inhibition of Erbb2 blocked the increase in ADAM12 message upon malignant progression. Similarly, human SCC and SCC cell lines had increased ADAM12 protein and transcripts when compared to normal controls. To determine whether Erbb2 up-regulation of ADAM12 contributed to malignant progression of skin cancer, Erbb2 expression was modulated in cultured SCC cells using forced over-expression or siRNA targeting, demonstrating up-regulation of ADAM12 by Erbb2. Furthermore, ADAM12 transfection or siRNA targeting revealed that ADAM12 increased both the migration and invasion of cutaneous SCC cells. Collectively, these results suggest Erbb2 up-regulation of ADAM12 as a novel mechanism contributing to the malignant progression of UV-induced skin cancer. Inhibition of Erbb2/HER2 reduced tumor burden, increased tumor regression, and delayed the progression of benign skin tumors to malignant SCC in UV-exposed mice. Inhibition of Erbb2 suppressed the increase in metalloproteinase ADAM12 expression in skin tumors, which in turn increased migration and tumor cell invasiveness. © 2014 Wiley Periodicals, Inc.

Human squamous cell carcinoma from skin: establishment and characterization of a new cell line (HSC-5).

PubMed

Hozumi, Y; Kondo, S; Shimoura, T; Aso, K

1990-03-01

A new cell line, designated as HSC-5 and derived from human skin squamous cell carcinoma (SCC), has been established in vitro and maintained proliferative in continuous tissue culture for over two years. The cells grow in a monolayer in vitro and have anaplastic epithelioid features. The doubling time was about 35 hr at the 30th passage. Chromosome analysis showed hypotetraploidy with a modal number of 76. A trial of transplantation of the cultured cells into nude mice was not successful. Analysis of cytokeratins from HSC-5 by two-dimensional gel electrophoresis revealed polypeptides No. 5, 8, 13, 18 and 19. The cell line is available to other investigators.

6-Gingerol Mediates its Anti Tumor Activities in Human Oral and Cervical Cancer Cell Lines through Apoptosis and Cell Cycle Arrest.

PubMed

Kapoor, Vaishali; Aggarwal, Sadhna; Das, Satya N

2016-04-01

6-Gingerol, a potent nutraceutical, has been shown to have antitumor activity in different tumors, although its mechanism of action is not well understood. In this study, we evaluated antitumor activities of 6-gingerol on human oral (SCC4, KB) and cervical cancer (HeLa) cell lines with or without wortmannin, rapamycin, and cisplatin. Tumor cell proliferation was observed using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H tetrazolium, inner salt assay, cell cycle analysis by propidium iodide labeling and flow cytometry, apoptosis by Annexin-V binding assay, and caspase activity by chemiluminescence assay. 6-Gingerol showed dose-dependent cytotoxicity in all three cell lines. Combinations of 6-gingerol with wortmannin and cisplatin showed additive effects, while with rapamycin, it showed 50% cytotoxicity that was equivalent to IC50 of 6-gingerol alone. Treatment with 6-gingerol resulted in G2-phase arrest in KB and HeLa cells and S-phase arrest in SCC4 cells. 6-Gingerol, wortmannin, and rapamycin treatment showed almost two-fold higher expression of caspase 3 in all cell lines. The results imply that 6-gingerol either alone or in combination with PI-3 K inhibitor and cisplatin may provide better therapeutic effects in oral and cervical carcinoma. Thus, 6-gingerol appears to be a safe and potent chemotherapeutic/chemopreventive compound acting through cell cycle arrest and induction of apoptosis in human oral and cervical tumor cells. Copyright © 2016 John Wiley & Sons, Ltd.

Survivin Modulates Squamous Cell Carcinoma-Derived Stem-Like Cell Proliferation, Viability and Tumor Formation in Vivo

PubMed Central

Lotti, Roberta; Palazzo, Elisabetta; Petrachi, Tiziana; Dallaglio, Katiuscia; Saltari, Annalisa; Truzzi, Francesca; Quadri, Marika; Puviani, Mario; Maiorana, Antonino; Marconi, Alessandra; Pincelli, Carlo

2016-01-01

Squamous Cell Carcinoma-derived Stem-like Cells (SCC-SC) originate from alterations in keratinocyte stem cells (KSC) gene expression and sustain tumor development, invasion and recurrence. Since survivin, a KSC marker, is highly expressed in SCC-SC, we evaluate its role in SCC-SC cell growth and SCC models. Survivin silencing by siRNA decreases clonal growth of SCC keratinocytes and viability of total, rapidly adhering (RAD) and non-RAD (NRAD) cells from primary SCC. Similarly, survivin silencing reduces the expression of stem cell markers (OCT4, NOTCH1, CD133, β1-integrin), while it increases the level of differentiation markers (K10, involucrin). Moreover, survivin silencing improves the malignant phenotype of SCC 3D-reconstruct, as demonstrated by reduced epidermal thickness, lower Ki-67 positive cell number, and decreased expression of MMP9 and psoriasin. Furthermore, survivin depletion by siRNA in RasG12V-IκBα-derived tumors leads to smaller tumor formation characterized by lower mitotic index and reduced expression of the tumor-associated marker HIF1α, VEGF and CD51. Therefore, our results indicate survivin as a key gene in regulating SCC cancer stem cell formation and cSCC development. PMID:26771605

A comparative study of the effectiveness of cisplatin and 5-fluorouracil on cutaneous squamous human carcinoma cell line: Potential chemotherapy alternative to surgery.

PubMed

Gil, S; Yébenes, M; Luelmo, J; Alsina, M; Sabés, M

2016-09-01

Surgery as treatment for local invasive cutaneous squamous cell carcinoma (cSCC) is not always feasible due to the age and/or the health status of patients. Thus, the investigation of new strategies to improve the quality of life of them is required. The aim of this work is to investigate two chemotherapy agents individually on cSCC cells with the purpose to provide a better understanding of the effectiveness underlying each one. The cisplatin effectiveness is compared at different times with that observed for the 5-fluorouracil treatment. The effectiveness of both was assessed by using flow cytometry to determine the survival cell ratio, and QBlue test to study the cell recovery ability after treatments. A significant increase in the number of apoptotic cells, especially 48 hours after treatments, has been detected. Despite this, cisplatin arises as the most promising agent for the treatment of local invasive cutaneous squamous cell carcinoma due to the fact that a lower concentration and time are required to observe a higher effectiveness on cells with respect to the 5-fluorouracil. An optimal cisplatin-based chemotherapy might provide a better outcome for patients affected by a local invasive cSCC rather than surgery. © 2016 Wiley Periodicals, Inc.

Cytotoxic effect of Erythroxylum daphnites extract is associated with G1 cell cycle arrest and apoptosis in oral squamous cell carcinoma.

PubMed

Elias, Silvia T; Macedo, Carolina C S; Simeoni, Luiz A; Silveira, Dâmaris; Magalhães, Pérola O; Lofrano-Porto, Adriana; Coletta, Ricardo D; Neves, Francisco A R; Guerra, Eliete N S

2016-01-01

Plant-derived molecules showing antineoplastic effects have recently gained increased attention as potential adjuvants to traditional therapies for various cancers. Cerrado biome in Brazil contains high floral biodiversity, but knowledge about the potential therapeutic effects of compounds derived from that flora is still limited. The present study investigated the antineoplastic activity of Erythroxylum daphnites Mart., a Brazilian native plant from Cerrado biome, in the SCC-9 oral squamous cell carcinoma cell line. Cells were treated with various concentrations of hexane extract of Erythroxylum daphnites leaves (EDH) and assessed for cytotoxicity, proliferation, and apoptosis. Thin layer chromatography was conducted to characterize the substances present in EDH. Our results showed that EDH exerted anti-proliferative effects in SCC-9 cells by stabilizing the cell cycle at G1 phase in association with reduced intracellular levels of cyclins D and E and increased level of p21. EDH also demonstrated pro-apoptotic properties, as shown by an increased expression of caspase-3. Triterpenes were the major constituents of EDH. Our findings demonstrated a cytotoxic effect of EDH against SCC-9 cells in vitro mediated by the restraint of cellular proliferation and induction of apoptosis. Taken together, these findings support EDH constituents as potential therapeutic adjuvants for oral cancer.

Modulation of 3-methylcholanthrene toxicity in cultured neoplastic keratinocytes by glucocorticoids and retinoids is not accounted for by macromolecular adduct formation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rubin, A.L.; Rice, R.H.

3-Methylcholanthrene (3-MC) greatly inhibits the growth of two lines of human squamous carcinoma cells, SCC-9 and SCC-12B{sub 2}. The degree of 3-MC-mediated inhibition, however, was markedly alleviated by inclusion of retinoic acid and hydrocortisone or dexamethasone in the culture medium. These physiological effectors, which are known to have opposing actions on keratinocyte character in SCC cells, did not significantly alter either aryl hydrocarbon hydroxylase activity or macromolecular adduct formation. Further analysis of the cellular responses indicated that hydrocortisone and, in some experiments, retinoids increased the growth rate in 3-MC-exposed cultures, while 3-MC increased the saturation density in retinoic acid-exposed cultures,more » an example of interference with a physiological response of the cells. These results indicate that alteration of the differentiated state, regardless of the direction of the change, can alter the sensitivity of these cells to toxic stimuli. Further investigation of the bases of such toxic responses and their modulation by the microenvironment may enhance our understanding of the target cell specificity of polycyclic aromatic hydrocarbons.« less

Up-regulation of antioxidant enzymes and coenzyme Q(10) in a human oral cancer cell line with acquired bleomycin resistance.

PubMed

Yen, Hsiu-Chuan; Li, Sin-Hua; Majima, Hideyuki J; Huang, Yu-Hsiang; Chen, Chiu-Ping; Liu, Chia-Chi; Tu, Ya-Chi; Chen, Chih-Wei

2011-06-01

Bleomycin (BLM) is an anti-cancer drug that can induce formation of reactive oxygen species (ROS). To investigate the association between up-regulation of antioxidant enzymes and coenzyme Q(10) (CoQ(10)) in acquired BLM resistance, one BLM-resistant clone, SBLM24 clone, was selected from a human oral cancer cell line, SCC61 clone. The BLM resistance of SBLM24 clone relative to a sub-clone of SCC61b cells was confirmed by analysis of clonogenic ability and cell cycle arrest. CoQ(10) levels and levels of Mn superoxide dismutase, glutathione peroxidase 1, catalase and thioredoxin reductase 1 were augmented in SBLM24 clone although there was also a mild increase in the expression of BLM hydrolase. Suppression of CoQ(10) levels by 4-aminobenzoate sensitized BLM-induced cytotoxicity. The results of suppression on enhanced ROS production by BLM and the cross-resistance to hydrogen peroxide in SBLM24 clone further demonstrated the development of adaptation to oxidative stress during the formation of acquired BLM resistance.

Interrelationships of somatic cell count, mastitis, and milk yield in a low somatic cell count herd.

PubMed

Deluyker, H A; Gay, J M; Weaver, L D

1993-11-01

In a high yielding low SCC herd, changes in milk yield associated with SCC and occurrence of clinical mastitis and differences in SCC with parity, clinical mastitis, and DIM were investigated. Milk yield data were obtained at every milking, and SCC was measured once every 48 h in 117 cows during the first 119 d postpartum. Effects of SCC and clinical mastitis on cumulative milk yield in the first 119 d postpartum were evaluated with least squares linear regression. Repeated measures ANOVA was used to detect changes in SCC. The SCC was highest at lactation onset, and cows with clinical mastitis had significantly higher SCC. During the 10 d prior to onset of clinical mastitis, SCC was higher in affected cows than in matched unaffected controls and surged just prior to diagnosis. During the 10-d period following a mastitis treatment, SCC differences between treated and control cows remained significant but became smaller with time and returned to the premastitis differences. Occurrence of clinical mastitis was associated with 5% milk yield loss. Cows with mean SCC > 245,000 cells/ml over the 119 d showed 6.2% yield loss compared with cows with SCC < or = 90,000 cells/ml. Cows with clinical mastitis had higher SCC prior to and following the end of treatment for mastitis than did controls. Clinical mastitis and SCC were associated with significant yield loss. Milk yield loss attributed to clinical mastitis was greater than that associated with elevated SCC (> 245,000 cells/ml) because a greater percentage of cows (26%) had clinical mastitis than elevated SCC (12.5%).

Lgr5-positive cells are cancer stem cells in skin squamous cell carcinoma.

PubMed

Liu, Shunli; Gong, Zhenyu; Chen, Mingrui; Liu, Benli; Bian, Donghui; Wu, Kai

2014-11-01

Cancer stem cells (CSCs) in most human tumors are commonly identified and enriched using similar strategies for identifying normal stem cells, including flow cytometry assays for side population, high aldehyde dehydrogenase (ALDH) activity, and CD133 positivity. Thus, development of a method for isolating a specific cancer using cancer-specific characteristic appears to be potentially important. Here, we reported extremely high Lgr5 levels in the specimen from skin squamous cell carcinoma (SCC) in patients. Using SCC cell line A431, we detected high Lgr5 and CD133 levels in ALDH-high or side population from these cancer cells. To figure out whether Lgr5 is a marker of CSCs in SCC, we transfected A431 cells with a Lgr5-creERT-2A-DTR/Cag-Loxp-GFP-STOP-Loxp-RFP plasmid and purified transfected cells (tA431) based on GFP by flow cytometry. 4-Hydroxytamoxifen (4-OHT) was given to label Lgr5-positive cells with RFP, for comparison to GFP-positive Lgr5-negative cells. Lgr5-positive cells grew significantly faster than Lgr5-negative cells, and the fold increase in growth of Lgr5-positive vs Lgr5-negative cells is significantly higher than SP vs non-SP, or ALDH-high vs ALDH-low, or CD133-positive vs CD133-negative cells. Moreover, in Lgr5-negative population, Lgr5-positive re-appeared in culture with time, suggesting that Lgr5-positive cells can be regenerated from Lgr5-negative cells. Furthermore, the growth of tA431 cells significantly decreased upon a single dose of diphtheria toxin (DT)/4-OHT to eliminate Lgr5-positive cell lineage, while multiple doses of DT/4-OHT nearly completely inhibited tA431 cell growth. Taken together, our data provide compelling data to demonstrate that Lgr5-positive cells are CSCs in skin SCC.

INF-γ sensitizes head and neck squamous cell carcinoma cells to chemotherapy-induced apoptosis and necroptosis through up-regulation of Egr-1.

PubMed

Xu, Bei; Shu, Yongqian; Liu, Peng

2014-11-01

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. Acquired resistance to standard chemotherapy accounts for most of treatment failure. Here we demonstrate that Interferon-γ (INF-γ) may up-regulate Egr-1 gene expression in HNSCC cell line SCC-25. Forced expression of Egr-1 sensitizes SCC-25 cells to chemotherapy-induced apoptosis and necroptosis, a novel form of programmed cell death. Egr-1 up-regulation also significantly increases the production of Thrombospondin-1 (TSP-1), a matricellular glycoprotein which has been described to induce cell death in HNSCC. Moreover, INF-γ-induced sensitization of cells to chemotherapy-mediated cell death and TSP-1 production could be markedly abolished by Egr-1 silencing. The present investigation provides the first evidence that INF-γ may sensitize HNSCC cells to chemotherapy-induced apoptosis and necroptosis through up-regulation of Egr-1. These data support the combination use of INF-γ and cytotoxic drugs for HNSCC Therapy.

Differential cytotoxicity of long-chain bases for human oral gingival epithelial keratinocytes, oral fibroblasts, and dendritic cells.

PubMed

Mehalick, Leslie A; Poulsen, Christopher; Fischer, Carol L; Lanzel, Emily A; Bates, Amber M; Walters, Katherine S; Cavanaugh, Joseph E; Guthmiller, Janet M; Johnson, Georgia K; Wertz, Philip W; Brogden, Kim A

2015-12-01

Long-chain bases, found in the oral cavity, have potent antimicrobial activity against oral pathogens. In an article associated with this dataset, Poulson and colleagues determined the cytotoxicities of long-chain bases (sphingosine, dihydrosphingosine, and phytosphingosine) for human oral gingival epithelial (GE) keratinocytes, oral gingival fibroblasts (GF), dendritic cells (DC), and squamous cell carcinoma (SCC) cell lines [1]. Poulson and colleagues found that GE keratinocytes were more resistant to long-chain bases as compared to GF, DC, and SCC cell lines [1]. In this study, we assess the susceptibility of DC to lower concentrations of long chain bases. 0.2-10.0 µM long-chain bases and GML were not cytotoxic to DC; 40.0-80.0 µM long-chain bases, but not GML, were cytotoxic for DC; and 80.0 µM long-chain bases were cytotoxic to DC and induced cellular damage and death in less than 20 mins. Overall, the LD50 of long-chain bases for GE keratinocytes, GF, and DC were considerably higher than their minimal inhibitory concentrations for oral pathogens, a finding important to pursuing their future potential in treating periodontal and oral infections.

Improved Fuzzy Logic System to Evaluate Milk Electrical Conductivity Signals from On-Line Sensors to Monitor Dairy Goat Mastitis.

PubMed

Zaninelli, Mauro; Tangorra, Francesco Maria; Costa, Annamaria; Rossi, Luciana; Dell'Orto, Vittorio; Savoini, Giovanni

2016-07-13

The aim of this study was to develop and test a new fuzzy logic model for monitoring the udder health status (HS) of goats. The model evaluated, as input variables, the milk electrical conductivity (EC) signal, acquired on-line for each gland by a dedicated sensor, the bandwidth length and the frequency and amplitude of the first main peak of the Fourier frequency spectrum of the recorded milk EC signal. Two foremilk gland samples were collected from eight Saanen goats for six months at morning milking (lactation stages (LS): 0-60 Days In Milking (DIM); 61-120 DIM; 121-180 DIM), for a total of 5592 samples. Bacteriological analyses and somatic cell counts (SCC) were used to define the HS of the glands. With negative bacteriological analyses and SCC < 1,000,000 cells/mL, glands were classified as healthy. When bacteriological analyses were positive or showed a SCC > 1,000,000 cells/mL, glands were classified as not healthy (NH). For each EC signal, an estimated EC value was calculated and a relative deviation was obtained. Furthermore, the Fourier frequency spectrum was evaluated and bandwidth length, frequency and amplitude of the first main peak were identified. Before using these indexes as input variables of the fuzzy logic model a linear mixed-effects model was developed to evaluate the acquired data considering the HS, LS and LS × HS as explanatory variables. Results showed that performance of a fuzzy logic model, in the monitoring of mammary gland HS, could be improved by the use of EC indexes derived from the Fourier frequency spectra of gland milk EC signals recorded by on-line EC sensors.

MMP-10 (Stromelysin-2) and MMP-21 in human and murine squamous cell cancer.

PubMed

Boyd, Sonja; Virolainen, Susanna; Pärssinen, Jenita; Skoog, Tiina; van Hogerlinden, Max; Latonen, Leena; Kyllönen, Lauri; Toftgard, Rune; Saarialho-Kere, Ulpu

2009-12-01

The squamous cell cancers (SCC) of renal transplant recipients are more aggressive and metastasize earlier than those of the non-immunocompromised population. Matrix metalloproteinases (MMPs) have a central role in tumor initiation, invasion and metastasis. Our aim was to compare the expression of MMPs-10, -12 and -21 in SCCs from immunosuppressed (IS) and control patients and the contribution of MMPs-10 and -21 to SCC development in the FVB/N-Tg(KRT5-Nfkbia)3Rto mouse line. Immunohistochemical analysis of 25 matched pairs of SCCs, nine of Bowen's disease and timed back skin biopsies of mice with selective inhibition of Rel/NF-kappaB signalling were performed. Semiquantitatively assessed stromal MMP-10 expression was higher (P = 0.009) in the control group when compared with IS patients. Tumor cell-derived MMP-10, -12 and -21 expression did not differ between the groups but stromal fibroblasts of the control SCCs tended to express MMP-21 more abundantly. MMP-10 expression was observed already in Bowen's disease while MMP-21 was absent. MMP-10 and -21 were present in inflammatory or stromal cells in ageing mice while dysplastic keratinocytes and invasive cancer were negative. Our results suggest that MMP-10 may be important in the initial stages of SCC progression and induced in the stroma relating to the general host-response reaction to skin cancer. MMP-21 does not associate with invasion of SCC but may be involved in keratinocyte differentiation.

1,25D3 potentiates cisplatin antitumor activity by p73 induction in a squamous cell carcinoma model

PubMed Central

Ma, Yingyu; Yu, Wei-Dong; Hershberger, Pamela A.; Flynn, Geraldine; Kong, Rui-Xian; Trump, Donald L.; Johnson, Candace S.

2008-01-01

1,25D3 exhibits anti-tumor activity in a variety of cancers including squamous cell carcinoma (SCC). Intrinsic resistance of SCC cells to cisplatin was observed and led to the investigation into whether 1,25D3 sensitizes SCC cells to cisplatin. Pretreatment with 1,25D3 followed by cisplatin enhanced growth inhibition in SCC cells compared with 1,25D3 alone, as assessed by cytotoxicity and in vitro clonogenic assays. In addition, 1,25D3 sensitized SCC cells to cisplatin-mediated apoptosis. Treatment of tumor-bearing C3H mice with 1,25D3 prior to cisplatin reduced clonogenic survival using in vivo excision clonogenic assay. These results were not observed in a 1,25D3-resistant SCC variant, indicating the critical role of 1,25D3 in sensitizing SCC cells to cisplatin. Further, a marked decrease in fractional tumor volume was observed when SCC tumor-bearing mice were treated with 1,25D3 prior to cisplatin as compared to either agent administered alone. Cisplatin has been shown to modulate p73 protein level in certain cancer cells. Our data showed that p73 level was not affected by cisplatin, but increased by 1,25D3 in SCC cells. Knocking down p73 by siRNA protected SCC cells against 1,25D3 and cisplatin-mediated clonogenic cell kill and apoptosis. Increasing p73 protein level by knocking down UFD2a, which mediates p73 degradation, promoted 1,25D3 and cisplatin-mediated clonogenic cell kill. These results suggest that 1,25D3 potentiates cisplatin anti-tumor activity in vitro and in vivo in a SCC model system, possibly through p73 induction and apoptosis. The combination treatment may provide a more effective therapeutic regimen in cancer treatment. PMID:18790784

A novel indole-3-carbinol derivative inhibits the growth of human oral squamous cell carcinoma in vitro.

PubMed

Weng, Jing-Ru; Bai, Li-Yuan; Omar, Hany A; Sargeant, Aaron M; Yeh, Ching-Tung; Chen, Yuan-Yin; Tsai, Ming-Hsui; Chiu, Chang-Fang

2010-10-01

Indole-3-carbinol (I3C), a naturally occurring phytochemical found in cruciferous vegetables, has received much attention due to its translational potential in cancer prevention and therapy. In this study, we investigated the antitumor effects of OSU-A9, a structurally optimized I3C derivative, in a panel of oral squamous cell carcinoma cell lines, SCC4, SCC15, and SCC2095. The antiproliferative effect of OSU-A9 was approximately two-orders-of-magnitude higher than that of I3C. Importantly, normal human oral keratinocytes were less sensitive to OSU-A9 than oral cancer cells. This antiproliferative effect of OSU-A9 was attributable to the induction of mitochondrial-dependent apoptosis as evidenced by sub-G1 accumulation of cells, poly ADP-ribose polymerase cleavage, and cytochrome c release from the mitochondria. OSU-A9 down regulates Akt and NF-κB signaling pathways, leading to changes in many downstream effectors involved in regulating cell cycle and apoptosis. Moreover, the observed down regulation of IKKα and IKKβ expression by OSU-A9 is not reported for I3C. OSU-A9 also induces both the production of reactive oxygen species and the endoplasmic reticulum stress. Taken together, these results suggest the translational value of OSU-A9 in oral squamous cell cancer therapy in the future. Copyright © 2010 Elsevier Ltd. All rights reserved.

Passive diffusion of naltrexone into human and animal cells and upregulation of cell proliferation.

PubMed

Cheng, Fan; McLaughlin, Patricia J; Banks, William A; Zagon, Ian S

2009-09-01

Naltrexone (NTX) is a potent opioid antagonist that promotes cell proliferation by upregulating DNA synthesis through displacement of the tonically active inhibitory peptide, opioid growth factor (OGF) from its receptor (OGFr). To investigate how NTX enters cells, NTX was fluorescently labeled [1-(N)-fluoresceinyl NTX thiosemicarbazone; FNTX] to study its uptake by living cultured cells. When human head and neck squamous cell carcinoma cell line (SCC-1) was incubated with FNTX for as little as 1 min, cells displayed nuclear and cytoplasmic staining of FNTX as determined by fluorescent deconvolution microscopy, with enrichment of fluorescent signal in the nucleus and nucleolus. The same temporal-spatial distribution of FNTX was detected in a human pancreatic cancer cell line (MIA PaCa-2), African green monkey kidney cell line (COS-7), and human mesenchymal stem cells (hMSCs). FNTX remained in cells for as long as 48 h. FNTX was internalized in SCC-1 cells when incubation occurred at 4 degrees C, with the signal being comparable to that recorded at 37 degrees C. A 100-fold excess of NTX or a variety of other opioid ligands did not alter the temporal-spatial distribution of FNTX. Neither fluorescein-labeled dextran nor fluorescein alone entered the cells. To study the effect of FNTX on DNA synthesis, cells incubated with FNTX at concentrations ranging from 10(-5) to 10(-8) M had a 5-bromo-2'-deoxyuridine index that was 39-82% greater than for vehicle-treated cells and was comparable to that of unlabeled NTX (37-70%). Taken together, these results suggested that NTX enters cells by passive diffusion in a nonsaturable manner.

Altered epigenetic regulation of homeobox genes in human oral squamous cell carcinoma cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Marcinkiewicz, Katarzyna M.; Gudas, Lorraine J., E-mail: ljgudas@med.cornell.edu

To gain insight into oral squamous cell carcinogenesis, we performed deep sequencing (RNAseq) of non-tumorigenic human OKF6-TERT1R and tumorigenic SCC-9 cells. Numerous homeobox genes are differentially expressed between OKF6-TERT1R and SCC-9 cells. Data from Oncomine, a cancer microarray database, also show that homeobox (HOX) genes are dysregulated in oral SCC patients. The activity of Polycomb repressive complexes (PRC), which causes epigenetic modifications, and retinoic acid (RA) signaling can control HOX gene transcription. HOXB7, HOXC10, HOXC13, and HOXD8 transcripts are higher in SCC-9 than in OKF6-TERT1R cells; using ChIP (chromatin immunoprecipitation) we detected PRC2 protein SUZ12 and the epigenetic H3K27me3 markmore » on histone H3 at these genes in OKF6-TERT1R, but not in SCC-9 cells. In contrast, IRX1, IRX4, SIX2 and TSHZ3 transcripts are lower in SCC-9 than in OKF6-TERT1R cells. We detected SUZ12 and the H3K27me3 mark at these genes in SCC-9, but not in OKF6-TERT1R cells. SUZ12 depletion increased HOXB7, HOXC10, HOXC13, and HOXD8 transcript levels and decreased the proliferation of OKF6-TERT1R cells. Transcriptional responses to RA are attenuated in SCC-9 versus OKF6-TERT1R cells. SUZ12 and H3K27me3 levels were not altered by RA at these HOX genes in SCC-9 and OKF6-TERT1R cells. We conclude that altered activity of PRC2 is associated with dysregulation of homeobox gene expression in human SCC cells, and that this dysregulation potentially plays a role in the neoplastic transformation of oral keratinocytes. - Highlights: • RNAseq elucidates differences between non-tumorigenic and tumorigenic oral keratinocytes. • Changes in HOX mRNA in SCC-9 vs. OKF6-TERT1R cells are a result of altered epigenetic regulation. • RNAseq shows that retinoic acid (RA) influences gene expression in both OKF6-TERT1R and SCC-9 cells.« less

Potential Role of S100A8 in Cutaneous Squamous Cell Carcinoma Differentiation.

PubMed

Shin, Jung-Min; Chang, In-Kyu; Lee, Young-Ho; Yeo, Min-Kyung; Kim, Jin-Man; Sohn, Kyung-Cheol; Im, Myung; Seo, Young-Joon; Kim, Chang-Deok; Lee, Jeung-Hoon; Lee, Young

2016-04-01

S100A8 is differentially expressed in various cell types and is associated with a number of malignant disorders. S100A8 may affect tumor biology. However, its role in cutaneous squamous cell carcinoma (SCC) is not well established. This study aims to investigate the relationship between S100A8 and cutaneous SCC development. We performed immunohistochemical staining to detect S100A8 expression in facial skin specimens of premalignant actinic keratosis (AK), malignant SCC, and normal tissues. In addition, we utilized postconfluence and high calcium-induced differentiation in a culture system model. Furthermore, we constructed a recombinant adenovirus expressing GFP-tagged S100A8 to investigate the role of S100A8 in SCC cell differentiation. S100A8 was significantly overexpressed in human cutaneous SCC compared to that in normal and AK tissues. S100A8 was gradually upregulated in SCC cells in a post-confluence-induced differentiation model. Overexpression of S100A8 in SCC cells induced by adenoviral transduction led to increased expression levels of differentiation markers, such as loricrin, involucrin, and filaggrin. S100A8 overexpression also increased loricrin and involucrin luciferase activity. S100A8 regulates cutaneous SCC differentiation and induces well-differentiated SCC formation in skin.

Regulation of Motility, Invasion and Metastatic Potential of Squamous Cell Carcinoma by 1,25D3

PubMed Central

Ma, Yingyu; Yu, Wei-Dong; Su, Bing; Seshadri, Mukund; Luo, Wei; Trump, Donald L.; Johnson, Candace S.

2012-01-01

BACKGROUND 1,25D3, the active metabolite of vitamin D, has been shown to exhibit broad spectrum anti-tumor activity in xenograft animal models. However, its activity against metastatic disease has not been extensively investigated. METHODS Squamous cell carcinoma (SCC) or 1,25D3-resistant variant SCC-DR cells were treated with 1,25D3. Actin organization was examined by immunofluorescence assay. Cell migration was assessed by “wound” healing and chemotactic migration assay. Cell invasion was assessed by Matrigel-based invasion assay and in situ zymography. MMP-2 and MMP-9 expression and secretion was examined by immunoblot analysis and ELISA, respectively. E-cadherin expression was assessed by flow cytometry, immunoblot analysis and immunohistochemistry. Knockdown of E-cadherin was achieved by siRNA. Experimental metastasis mouse model was done by intravenous injection of tumor cells. Lung tumor development was assessed by magnetic resonance imaging, gross observation and histology. RESULTS SCC cellular morphology and actin organization were altered by 10 nM of 1,25D3. 1,25D3 inhibited SCC cell motility and invasion, which was associated with reduced expression and secretion of MMP-2 and MMP-9. 1,25D3 promoted the expression of E-cadherin. These findings were not observed in SCC-DR cells. Knock down of E-cadherin rescued 1,25D3-inhibited cell migration. Intravenous injection of SCC or SCC-DR cells resulted in the establishment of extensive pulmonary lesions in saline-treated C3H mice. Treatment with 1,25D3 resulted in a marked reduction in the formation of lung tumor colonies in animals injected with SCC but not SCC-DR cells. CONCLUSIONS 1,25D3 suppresses SCC cell motility, invasion and metastasis, partially through the promotion of E-cadherin-mediated cell-cell adhesion. PMID:22833444

The relationship between solar keratoses and squamous cell carcinomas among Japanese.

PubMed

Takemiya, M; Ohtsuka, H; Miki, Y

1990-06-01

Between 1976 and 1988, 135 patients with solar keratosis (SK) and 53 patients with squamous cell carcinoma (SCC) on the sun-exposed skin, but without apparent preceding diseases such as burn scars, chronic radiodermatitis, chronic arsenic poisoning, or xeroderma pigmentosum, were encountered. Sixteen of the SCC patients also had SK on other areas of sun-exposed skin. There were 31 SCC patients also showing SK (SK-SCC) and 22 SCC not showing SK (DN-SCC) within the same histologic sections. The mean ages of the patients with SK-SCC and with DN-SCC were similar. Metastases to regional lymph nodes were observed in 5 SK-SCC patients, of whom 3 died of the disease, and in 5 DN-SCC patients, of whom 4 died of the disease. The five-year post-operative survival rates were 70% in SK-SCC and 74% in DN-SCC; the ten-year post-operative survival rates were 70% in SK-SCC and 44% in DN-SCC.

Response of head and neck squamous cell carcinoma cells carrying PIK3CA mutations to selected targeted therapies.

PubMed

Wirtz, Eric D; Hoshino, Daisuke; Maldonado, Anthony T; Tyson, Darren R; Weaver, Alissa M

2015-06-01

The PIK3CA mutation is one of the most common mutations in head and neck squamous cell carcinoma (HNSCC). Through this research we attempt to elicit the role of oncogene dependence and effects of targeted therapy on this PIK3CA mutation. (1) To determine the role of oncogene dependence on PIK3CA-one of the more common and targetable oncogenes in HNSCC, and (2) to evaluate the consequence of this oncogene on the effectiveness of newly developed targeted therapies. This was a cell culture-based, in vitro study performed at an academic research laboratory assessing the viability of PIK3CA-mutated head and neck cell lines when treated with targeted therapy. PIK3CA-mutated head and neck cell lines were treated with 17-AAG, GDC-0941, trametinib, and BEZ-235. Assessment of cell viability of HNSCC cell lines characterized for PIK3CA mutations or SCC25 cells engineered to express the PIK3CA hotspot mutations E545K or H1047R. Surprisingly, in engineered cell lines, the hotspot E545K and H1047R mutations conferred increased, rather than reduced, IC50 assay measurements when treated with the respective HSP90, PI3K, and MEK inhibitors, 17-AAG, GDC-0941, and trametinib, compared with the SCC25 control cell lines. When treated with BEZ-235, H1047R-expressing cell lines showed increased sensitivity to inhibition compared with control, whereas those expressing E545K showed slightly increased sensitivity of unclear significance. (1) The PIK3CA mutations within our engineered cell model did not lead to enhanced oncogene-dependent cell death when treated with direct inhibition of the PI3K enzyme yet did show increased sensitivity compared with control with dual PI3K/mTOR inhibition. (2) Oncogene addiction to PIK3CA hotspot mutations, if it occurs, is likely to evolve in vivo in the context of additional molecular changes that remain to be identified. Additional study is required to develop new model systems and approaches to determine the role of targeted therapy in the treatment of PI3K-overactive HNSCC tumors.

PWSCC Susceptibility in Heat Affected Zones of Alloy 600

NASA Astrophysics Data System (ADS)

Couvant, Thierry; Brossier, Thomas; Cossange, Christian

The recent field experience and several experimental results have shown the possible deleterious effect of a heat affected zone (HAZ) induced by welding on the susceptibility to the stress corrosion cracking (SCC) of Alloy 600 of bottom penetrations exposed to primary water of PWRs. This work tried to quantify the increasing susceptibility to initiation and crack propagation in 600/182 HAZ. The rolled plate did not exhibit any susceptibility to SCC except for a cold work higher than 10% typically. By contrast, the weld metal was well known for its high susceptibility to SCC. Metallurgical and mechanical characterizations of the HAZ indicated a slight gradient of Vickers micro hardness close to the fusion line (up to few mm) and a lack of intergranular precipitates up to 500 µm from the fusion line. SCC tests clearly demonstrated that a non-susceptible plate may exhibit a significant susceptibility to SCC propagation in the HAZ. Results of initiation tests did not allow to observe any SCC in the base metal, due to the high susceptibility to SCC of the weld.

Increased ICAM-1 Expression in Transformed Human Oral Epithelial Cells: Molecular Mechanism and Functional Role in Peripheral Blood Mononuclear Cell Adhesion and Lymphokine-Activated-Killer Cell Cytotoxicity

PubMed Central

Huang, George T.-J.; Zhang, Xinli; Park, No-Hee

2012-01-01

The intercellular adhesion molecule-1 (ICAM-1, CD54) serves as a counter-receptor for the β2-integrins, LFA-1 and Mac-1, which are expressed on leukocytes. Although expression of ICAM-1 on tumor cells has a role in tumor progression and development, information on ICAM-1 expression and its role in oral cancer has not been established. Normal human oral keratinocytes (NHOK), human papilloma virus (HPV)-immortalized human oral keratinocyte lines (HOK-16B, HOK-18A, and HOK-18C), and six human oral neoplastic cell lines (HOK-16B-BaP-T1, SCC-4, SCC-9, HEp-2, Tu-177 and 1483) were used to study ICAM-1 expression and its functional role in vitro. Our results demonstrated that NHOK express negligible levels of ICAM-1, whereas immortalized human oral keratinocytes and cancer cells express significantly higher levels of ICAM-1, except for HOK-16B-BaP-T1 and HEp-2. Altered mRNA half-lives did not fully account for the increased accumulation of ICAM-1 mRNA. Adhesion of peripheral blood mononuclear cells (PBMC) to epithelial cells correlated with cell surface ICAM-1 expression levels. This adhesion was inhibited by antibodies specific for either ICAM-1 or LFA-1/Mac-1, suggesting a role for these molecules in adhesion. In contrast, lymphokine-activated-killer (LAK) cell cytotoxic killing of epithelial cells did not correlate with ICAM-1 levels or with adhesion. Nonetheless, within each cell line, blocking of ICAM-1 or LFA-1/Mac-1 reduced LAK cells killing, suggesting that ICAM-1 is involved in mediating this killing. PMID:10938387

Identification of the optimal therapeutic antibody for fluorescent imaging of cutaneous squamous cell carcinoma

PubMed Central

Day, Kristine E.; Beck, Lauren N.; Heath, C. Hope; Huang, Conway C.; Zinn, Kurt R.; Rosenthal, Eben L.

2013-01-01

Intraoperative, real-time fluorescence imaging may significantly improve tumor visualization and resection and postoperatively, in pathological assessment. To this end, we sought to determine the optimal FDA approved therapeutic monoclonal antibody for optical imaging of human cutaneous squamous cell carcinoma (cSCC). A near-infrared (NIR) fluorescent probe (IRDye800) was covalently linked to bevacizumab, panitumumab or tocilizumab and injected systemically into immunodeficient mice bearing either cutaneous tumor cell lines (SCC13) or cutaneous human tumor explants. Tumors were then imaged and resected under fluorescent guidance with the SPY, an FDA-approved intraoperative imaging system, and the Pearl Impulse small animal imaging system. All fluorescently labeled antibodies delineated normal tissue from tumor in SCC13 xenografts based on tumor-to-background (TBR) ratios. The conjugated antibodies produced TBRs of 1.2–2 using SPY and 1.6–3.6 using Pearl; in comparison, isotype control antibody IgG-IRDye produced TBRs of 1.0 (SPY) and 0.98 (Pearl). Comparison between antibodies revealed them to be roughly equivalent for imaging purposes with both the SPY and Pearl (p = 0.89 SPY, p = 0.99 Pearl; one way ANOVA). Human tumor explants were also imaged and tumor detection was highest with panitumumab-IRDye800 when using the SPY (TBR 3.0) and Pearl (TBR 4.0). These data suggest that FDA approved antibodies may be clinically used for intraoperative detection of cSCC. PMID:23298904

Differential cytotoxicity of long-chain bases for human oral gingival epithelial keratinocytes, oral fibroblasts, and dendritic cells

PubMed Central

Mehalick, Leslie A.; Poulsen, Christopher; Fischer, Carol L.; Lanzel, Emily A.; Bates, Amber M.; Walters, Katherine S.; Cavanaugh, Joseph E.; Guthmiller, Janet M.; Johnson, Georgia K.; Wertz, Philip W.; Brogden, Kim A.

2015-01-01

Long-chain bases, found in the oral cavity, have potent antimicrobial activity against oral pathogens. In an article associated with this dataset, Poulson and colleagues determined the cytotoxicities of long-chain bases (sphingosine, dihydrosphingosine, and phytosphingosine) for human oral gingival epithelial (GE) keratinocytes, oral gingival fibroblasts (GF), dendritic cells (DC), and squamous cell carcinoma (SCC) cell lines [1]. Poulson and colleagues found that GE keratinocytes were more resistant to long-chain bases as compared to GF, DC, and SCC cell lines [1]. In this study, we assess the susceptibility of DC to lower concentrations of long chain bases. 0.2–10.0 µM long-chain bases and GML were not cytotoxic to DC; 40.0–80.0 µM long-chain bases, but not GML, were cytotoxic for DC; and 80.0 µM long-chain bases were cytotoxic to DC and induced cellular damage and death in less than 20 mins. Overall, the LD50 of long-chain bases for GE keratinocytes, GF, and DC were considerably higher than their minimal inhibitory concentrations for oral pathogens, a finding important to pursuing their future potential in treating periodontal and oral infections. PMID:26550599

Potential Role of S100A8 in Cutaneous Squamous Cell Carcinoma Differentiation

PubMed Central

Shin, Jung-Min; Chang, In-Kyu; Lee, Young-Ho; Yeo, Min-Kyung; Kim, Jin-Man; Sohn, Kyung-Cheol; Im, Myung; Seo, Young-Joon; Kim, Chang-Deok; Lee, Jeung-Hoon

2016-01-01

Background S100A8 is differentially expressed in various cell types and is associated with a number of malignant disorders. S100A8 may affect tumor biology. However, its role in cutaneous squamous cell carcinoma (SCC) is not well established. Objective This study aims to investigate the relationship between S100A8 and cutaneous SCC development. Methods We performed immunohistochemical staining to detect S100A8 expression in facial skin specimens of premalignant actinic keratosis (AK), malignant SCC, and normal tissues. In addition, we utilized postconfluence and high calcium-induced differentiation in a culture system model. Furthermore, we constructed a recombinant adenovirus expressing GFP-tagged S100A8 to investigate the role of S100A8 in SCC cell differentiation. Results S100A8 was significantly overexpressed in human cutaneous SCC compared to that in normal and AK tissues. S100A8 was gradually upregulated in SCC cells in a post-confluence-induced differentiation model. Overexpression of S100A8 in SCC cells induced by adenoviral transduction led to increased expression levels of differentiation markers, such as loricrin, involucrin, and filaggrin. S100A8 overexpression also increased loricrin and involucrin luciferase activity. Conclusion S100A8 regulates cutaneous SCC differentiation and induces well-differentiated SCC formation in skin. PMID:27081264

Primary intraosseous squamous cell carcinoma in odontogenic keratocyst: A rare entity

PubMed Central

Saxena, Chitrapriya; Aggarwal, Pooja; Wadhwan, Vijay; Bansal, Vishal

2015-01-01

Squamous cell carcinoma (SCC) arising from the wall of an odontogenic cyst (also known as primary intraosseous carcinoma) is a rare tumor which occurs only in jaw bones. This tumor was first described by Loos in 1913 as a central epidermoid carcinoma of the jaw. Primary intraosseous carcinomas (PIOC) may theoretically arise from the lining of an odontogenic cyst or de novo from presumed odontogenic cell rests. According to the new histological classification of tumors of the World Health Organization, odontogenic keratocyst is nowadays considered a specific odontogenic tumor and the PIOC derived from it is considered as a specific entity which is different from other PIOCs derived from the odontogenic cysts. The following report describes a case of such extremely rare entity that is primary intraosseous SCC of the mandible derived from an OKC in a 60-year-old male patient with brief review of literature. PMID:26980976

CD10-bearing fibroblast inhibits matrigel invasive potency of interleukin-1α-producing squamous cell carcinoma by diminishing substance P levels in the tumor microenvironment.

PubMed

Xie, Lining; Moroi, Yoichi; Tsuji, Gaku; Liu, Min; Hayashida, Sayaka; Takahara, Masakazu; Fukagawa, Shuji; Takeuchi, Satoshi; Shan, Baoen; Nakahara, Takeshi; Uchi, Hiroshi; Yokomizo, Takehiko; Furue, Masutaka

2010-12-01

CD10 is a neutral endopeptidase, which cleaves various peptide substrates including substance P. CD10 expression has been detected in peritumoral fibroblasts (Fb) within the invasive area of various cancers such as squamous cell carcinoma (SCC). However, the biological significance of CD10-bearing Fb remains largely unknown. We examined dynamic interactions of Fb with tumorigenic A431 SCC cells or non-tumorigenic HaCaT squamous cells. The SCC and HaCaT cells did not synthesize CD10, while Fb constitutively expressed CD10. When co-cultured, SCC markedly upregulated fibroblastic CD10 expression compared with HaCaT, which was mainly attributable to SCC-derived interleukin-1α (IL-1α). Both SCC and Fb autonomously secreted substance P, which eventually enhanced the invasive capacity of SCC in a matrigel invasion assay by upregulating matrix metalloproteinase (MMP)-1 and MMP-2, but not MMP-9. Transfection of siRNA for CD10 successfully knocked down the CD10 expression in Fb (CD10ND-Fb). In the presence of CD10ND-Fb, substance P levels in supernatants as well as MMP production and the invasive potency of SCC were significantly augmented compared with control scramble RNA-transfected Fb. We also transfected CD10 vector to Fb and found that the matrigel invasive ability of SCC cells was downregulated co-cultured with CD10 vector-transfected Fb rather than empty vector-transfected Fb. In conclusion, the CD10-bearing Fb generated by SCC-derived IL-1 inhibited the invasive capacity of SCC by diminishing the microenvironmental concentration of substance P. © 2010 Japanese Cancer Association.

A Tetrameric Peptide Derived from Bovine Lactoferricin Exhibits Specific Cytotoxic Effects against Oral Squamous-Cell Carcinoma Cell Lines.

PubMed

Solarte, Víctor A; Rosas, Jaiver E; Rivera, Zuly J; Arango-Rodríguez, Martha L; García, Javier E; Vernot, Jean-Paul

2015-01-01

Several short linear peptides derived from cyclic bovine lactoferricin were synthesized and tested for their cytotoxic effect against the oral cavity squamous-cell carcinoma (OSCC) cell lines CAL27 and SCC15. As a control, an immortalized and nontumorigenic cell line, Het-1A, was used. Linear peptides based on the RRWQWR core sequence showed a moderate cytotoxic effect and specificity towards tumorigenic cells. A tetrameric peptide, LfcinB(20-25)4, containing the RRWQWR motif, exhibited greater cytotoxic activity (>90%) in both OSCC cell lines compared to the linear lactoferricin peptide or the lactoferrin protein. Additionally, this tetrameric peptide showed the highest specificity towards tumorigenic cells among the tested peptides. Interestingly, this effect was very fast, with cell shrinkage, severe damage to cell membrane permeability, and lysis within one hour of treatment. Our results are consistent with a necrotic effect rather than an apoptotic one and suggest that this tetrameric peptide could be considered as a new candidate for the therapeutic treatment of OSCC.

Glabridin induces apoptosis and cell cycle arrest in oral cancer cells through the JNK1/2 signaling pathway.

PubMed

Chen, Chang-Tai; Chen, Yi-Tzu; Hsieh, Yi-Hsien; Weng, Chia-Jui; Yeh, Jung-Chun; Yang, Shun-Fa; Lin, Chiao-Wen; Yang, Jia-Sin

2018-06-01

Glabridin, a flavonoid extracted from licorice (Glycyrrhiza glabra), possesses various biological properties, including anticancer activities. However, the effect of glabridin on oral cancer cell apoptosis and the underlying molecular mechanisms has not been elucidated. In this study, we demonstrated that glabridin treatment significantly inhibits cell proliferation in human oral cancer SCC-9 and SAS cell lines. Flow cytometric assays demonstrated that glabridin induced several features of apoptosis, such as sub-G1 phase cell increase and phosphatidylserine externalization. Furthermore, glabridin induced apoptosis dose-dependently in SCC-9 cells through caspase-3, -8, and -9 activation and poly (ADP-ribose) polymerase cleavage. Moreover, glabridin increased the phosphorylation of the extracellular signal-regulated kinase, p38, and c-Jun N-terminal kinase (JNK) pathways in a dose-dependent manner. Moreover, the inhibition of the JNK1/2 inhibitor significantly reversed the glabridin-induced activation of the caspase pathway. In conclusion, our findings suggest that glabridin induces oral cancer cell apoptosis through the JNK1/2 pathway and is a potential therapeutic agent for oral cancer. © 2018 Wiley Periodicals, Inc.

Casticin impairs cell growth and induces cell apoptosis via cell cycle arrest in human oral cancer SCC-4 cells.

PubMed

Chou, Guan-Ling; Peng, Shu-Fen; Liao, Ching-Lung; Ho, Heng-Chien; Lu, Kung-Wen; Lien, Jin-Cherng; Fan, Ming-Jen; La, Kuang-Chi; Chung, Jing-Gung

2018-02-01

Casticin, a polymethoxyflavone, present in natural plants, has been shown to have biological activities including anti-cancer activities. Herein, we investigated the anti-oral cancer activity of casticin on SCC-4 cells in vitro. Viable cells, cell cycle distribution, apoptotic cell death, reactive oxygen species (ROS) production, and Ca 2+ production, levels of ΔΨ m and caspase activity were measured by flow cytometric assay. Cell apoptosis associated protein expressions were examined by Western blotting and confocal laser microscopy. Results indicated that casticin induced cell morphological changes, DNA condensation and damage, decreased the total viable cells, induced G 2 /M phase arrest in SCC-4 cells. Casticin promoted ROS and Ca 2+ productions, decreases the levels of ΔΨ m , promoted caspase-3, -8, and -9 activities in SCC-4 cells. Western blotting assay demonstrated that casticin affect protein level associated with G2/M phase arrest and apoptosis. Confocal laser microscopy also confirmed that casticin increased the translocation of AIF and cytochrome c in SCC-4 cells. In conclusion, casticin decreased cell number through G 2 /M phase arrest and the induction of cell apoptosis through caspase- and mitochondria-dependent pathways in SCC-4 cells. © 2017 Wiley Periodicals, Inc.

Afatinib radiosensitizes head and neck squamous cell carcinoma cells by targeting cancer stem cells.

PubMed

Macha, Muzafar A; Rachagani, Satyanarayana; Qazi, Asif Khurshid; Jahan, Rahat; Gupta, Suprit; Patel, Anery; Seshacharyulu, Parthasarathy; Lin, Chi; Li, Sicong; Wang, Shuo; Verma, Vivek; Kishida, Shosei; Kishida, Michiko; Nakamura, Norifumi; Kibe, Toshiro; Lydiatt, William M; Smith, Russell B; Ganti, Apar K; Jones, Dwight T; Batra, Surinder K; Jain, Maneesh

2017-03-28

The dismal prognosis of locally advanced and metastatic squamous cell carcinoma of the head and neck (HNSCC) is primarily due to the development of resistance to chemoradiation therapy (CRT). Deregulation of Epidermal Growth Factor Receptor (EGFR) signaling is involved in HNSCC pathogenesis by regulating cell survival, cancer stem cells (CSCs), and resistance to CRT. Here we investigated the radiosensitizing activity of the pan-EGFR inhibitor afatinib in HNSCC in vitro and in vivo. Our results showed strong antiproliferative effects of afatinib in HNSCC SCC1 and SCC10B cells, compared to immortalized normal oral epithelial cells MOE1a and MOE1b. Comparative analysis revealed stronger antitumor effects with afatinib than observed with erlotinib. Furthermore, afatinib enhanced in vitro radiosensitivity of SCC1 and SCC10B cells by inducing mesenchymal to epithelial transition, G1 cell cycle arrest, and the attenuating ionizing radiation (IR)-induced activation of DNA double strand break repair (DSB) ATM/ATR/CHK2/BRCA1 pathway. Our studies also revealed the effect of afatinib on tumor sphere- and colony-forming capabilities of cancer stem cells (CSCs), and decreased IR-induced CSC population in SCC1 and SCC10B cells. Furthermore, we observed that a combination of afatinib with IR significantly reduced SCC1 xenograft tumors (median weight of 168.25 ± 20.85 mg; p = 0.05) compared to afatinib (280.07 ± 20.54 mg) or IR alone (324.91 ± 28.08 mg). Immunohistochemical analysis of SCC1 tumor xenografts demonstrated downregulation of the expression of IR-induced pEGFR1, ALDH1 and upregulation of phosphorylated γH2AX by afatinib. Overall, afatinib reduces tumorigenicity and radiosensitizes HNSCC cells. It holds promise for future clinical development as a novel radiosensitizer by improving CSC eradication.

Cancer Stem-like Cells Act via Distinct Signaling Pathways in Promoting Late Stages of Malignant Progression.

PubMed

da Silva-Diz, Victoria; Simón-Extremera, Pilar; Bernat-Peguera, Adrià; de Sostoa, Jana; Urpí, Maria; Penín, Rosa M; Sidelnikova, Diana Pérez; Bermejo, Oriol; Viñals, Joan Maria; Rodolosse, Annie; González-Suárez, Eva; Moruno, Antonio Gómez; Pujana, Miguel Ángel; Esteller, Manel; Villanueva, Alberto; Viñals, Francesc; Muñoz, Purificación

2016-03-01

Cancer stem-like cells (CSC) play key roles in long-term tumor propagation and metastasis, but their dynamics during disease progression are not understood. Tumor relapse in patients with initially excised skin squamous cell carcinomas (SCC) is characterized by increased metastatic potential, and SCC progression is associated with an expansion of CSC. Here, we used genetically and chemically-induced mouse models of skin SCC to investigate the signaling pathways contributing to CSC function during disease progression. We found that CSC regulatory mechanisms change in advanced SCC, correlating with aggressive tumor growth and enhanced metastasis. β-Catenin and EGFR signaling, induced in early SCC CSC, were downregulated in advanced SCC. Instead, autocrine FGFR1 and PDGFRα signaling, which have not been previously associated with skin SCC CSC, were upregulated in late CSC and promoted tumor growth and metastasis, respectively. Finally, high-grade and recurrent human skin SCC recapitulated the signaling changes observed in advanced mouse SCC. Collectively, our findings suggest a stage-specific switch in CSC regulation during disease progression that could be therapeutically exploited by targeting the PDGFR and FGFR1 pathways to block relapse and metastasis of advanced human skin SCC. ©2015 American Association for Cancer Research.

Differentiation-induced skin cancer suppression by FOS, p53, and TACE/ADAM17

PubMed Central

Guinea-Viniegra, Juan; Zenz, Rainer; Scheuch, Harald; Jiménez, María; Bakiri, Latifa; Petzelbauer, Peter; Wagner, Erwin F.

2012-01-01

Squamous cell carcinomas (SCCs) are heterogeneous and aggressive skin tumors for which innovative, targeted therapies are needed. Here, we identify a p53/TACE pathway that is negatively regulated by FOS and show that the FOS/p53/TACE axis suppresses SCC by inducing differentiation. We found that epidermal Fos deletion in mouse tumor models or pharmacological FOS/AP-1 inhibition in human SCC cell lines induced p53 expression. Epidermal cell differentiation and skin tumor suppression were caused by a p53-dependent transcriptional activation of the metalloprotease TACE/ADAM17 (TNF-α–converting enzyme), a previously unknown p53 target gene that was required for NOTCH1 activation. Although half of cutaneous human SCCs display p53-inactivating mutations, restoring p53/TACE activity in mouse and human skin SCCs induced tumor cell differentiation independently of the p53 status. We propose FOS/AP-1 inhibition or p53/TACE reactivating strategies as differentiation-inducing therapies for SCCs. PMID:22772468

Estimating milk yield and value losses from increased somatic cell count on US dairy farms.

PubMed

Hadrich, J C; Wolf, C A; Lombard, J; Dolak, T M

2018-04-01

Milk loss due to increased somatic cell counts (SCC) results in economic losses for dairy producers. This research uses 10 mo of consecutive dairy herd improvement data from 2013 and 2014 to estimate milk yield loss using SCC as a proxy for clinical and subclinical mastitis. A fixed effects regression was used to examine factors that affected milk yield while controlling for herd-level management. Breed, milking frequency, days in milk, seasonality, SCC, cumulative months with SCC greater than 100,000 cells/mL, lactation, and herd size were variables included in the regression analysis. The cumulative months with SCC above a threshold was included as a proxy for chronic mastitis. Milk yield loss increased as the number of test days with SCC ≥100,000 cells/mL increased. Results from the regression were used to estimate a monetary value of milk loss related to SCC as a function of cow and operation related explanatory variables for a representative dairy cow. The largest losses occurred from increased cumulative test days with a SCC ≥100,000 cells/mL, with daily losses of $1.20/cow per day in the first month to $2.06/cow per day in mo 10. Results demonstrate the importance of including the duration of months above a threshold SCC when estimating milk yield losses. Cows with chronic mastitis, measured by increased consecutive test days with SCC ≥100,000 cells/mL, resulted in higher milk losses than cows with a new infection. This provides farm managers with a method to evaluate the trade-off between treatment and culling decisions as it relates to mastitis control and early detection. Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Tumor necrosis factor-alpha stimulates the production of squamous cell carcinoma antigen in normal squamous cells.

PubMed

Numa, F; Takeda, O; Nakata, M; Nawata, S; Tsunaga, N; Hirabayashi, K; Suminami, Y; Kato, H; Hamanaka, S

1996-01-01

Squamous cell carcinoma (SCC) antigen, a tumor marker of squamous cell carcinoma, is also increased in several nonmalignant skin lesions, e.g. pemphigus. The aim of the present investigation was to determine if tumor necrosis factor-alpha (TNF-alpha), one of the important environmental factors, stimulated the production of SCC antigen in the normal squamous cells. The exposure of normal human epidermal keratinocytes to TNF-alpha (100 IU/ml) for 72 h greatly increased the SCC antigen production. The stimulatory effect of TNF-alpha (1,000 IU/ml) on the production of SCC antigen was also observed in the normal squamous epithelium tissue. These results would be helpful for understanding the increase of SCC antigen in several nonmalignant skin disorders.

Evaluation of the Fourier Frequency Spectrum Peaks of Milk Electrical Conductivity Signals as Indexes to Monitor the Dairy Goats' Health Status by On-Line Sensors.

PubMed

Zaninelli, Mauro; Agazzi, Alessandro; Costa, Annamaria; Tangorra, Francesco Maria; Rossi, Luciana; Savoini, Giovanni

2015-08-21

The aim of this study is a further characterization of the electrical conductivity (EC) signal of goat milk, acquired on-line by EC sensors, to identify new indexes representative of the EC variations that can be observed during milking, when considering not healthy (NH) glands. Two foremilk gland samples from 42 Saanen goats, were collected for three consecutive weeks and for three different lactation stages (LS: 0-60 Days In Milking (DIM); 61-120 DIM; 121-180 DIM), for a total amount of 1512 samples. Bacteriological analyses and somatic cells counts (SCC) were used to define the health status of the glands. With negative bacteriological analyses and SCC < 1,000,000 cells/mL, glands were classified as healthy. When bacteriological analyses were positive or showed a SCC > 1,000,000 cells/mL, glands were classified as NH. For each milk EC signal, acquired on-line and for each gland considered, the Fourier frequency spectrum of the signal was calculated and three representative frequency peaks were identified. To evaluate data acquired a MIXED procedure was used considering the HS, LS and LS × HS as explanatory variables in the statistical model.Results showed that the studied frequency peaks had a significant relationship with the gland's health status. Results also explained how the milk EC signals' pattern change in case of NH glands. In fact, it is characterized by slower fluctuations (due to the lower frequencies of the peaks) and by an irregular trend (due to the higher amplitudes of all the main frequency peaks). Therefore, these frequency peaks could be used as new indexes to improve the performances of algorithms based on multivariate models which evaluate the health status of dairy goats through the use of gland milk EC sensors.

Evaluation of the Fourier Frequency Spectrum Peaks of Milk Electrical Conductivity Signals as Indexes to Monitor the Dairy Goats’ Health Status by On-Line Sensors

PubMed Central

Zaninelli, Mauro; Agazzi, Alessandro; Costa, Annamaria; Tangorra, Francesco Maria; Rossi, Luciana; Savoini, Giovanni

2015-01-01

The aim of this study is a further characterization of the electrical conductivity (EC) signal of goat milk, acquired on-line by EC sensors, to identify new indexes representative of the EC variations that can be observed during milking, when considering not healthy (NH) glands. Two foremilk gland samples from 42 Saanen goats, were collected for three consecutive weeks and for three different lactation stages (LS: 0–60 Days In Milking (DIM); 61–120 DIM; 121–180 DIM), for a total amount of 1512 samples. Bacteriological analyses and somatic cells counts (SCC) were used to define the health status of the glands. With negative bacteriological analyses and SCC < 1,000,000 cells/mL, glands were classified as healthy. When bacteriological analyses were positive or showed a SCC > 1,000,000 cells/mL, glands were classified as NH. For each milk EC signal, acquired on-line and for each gland considered, the Fourier frequency spectrum of the signal was calculated and three representative frequency peaks were identified. To evaluate data acquired a MIXED procedure was used considering the HS, LS and LS × HS as explanatory variables in the statistical model.Results showed that the studied frequency peaks had a significant relationship with the gland’s health status. Results also explained how the milk EC signals’ pattern change in case of NH glands. In fact, it is characterized by slower fluctuations (due to the lower frequencies of the peaks) and by an irregular trend (due to the higher amplitudes of all the main frequency peaks). Therefore, these frequency peaks could be used as new indexes to improve the performances of algorithms based on multivariate models which evaluate the health status of dairy goats through the use of gland milk EC sensors. PMID:26307993

Evaluation of T-lymphocyte subpopulations in actinic keratosis, in situ and invasive squamous cell carcinoma of the skin.

PubMed

Stravodimou, Aristea; Tzelepi, Vassiliki; Papadaki, Helen; Mouzaki, Athanasia; Georgiou, Sophia; Melachrinou, Maria; Kourea, Eleni P

2018-05-01

Tumor infiltrating lymphocytes (TILs) represent important regulators of carcinogenesis. Cutaneous invasive squamous cell carcinoma (inSCC) develops through precursor lesions, namely in situ squamous cell carcinoma (isSCC) and actinic keratosis (AK), representing a natural model of carcinogenesis. The study evaluates TIL subpopulations in inSCC and its precursors by comparing 2 semiquantitative scoring systems, and assesses the presence of regulatory T-cells (Tregs) in these lesions. Paraffin sections from 33 cases of AK, 19 isSCCs and 34 inSCCs with adjacent precursor lesions or normal skin (NS) were immunostained for CD3, CD4, CD8 and Foxp3. TIL subgroups were evaluated by the semiquantitative Klintrup-Mäkinen (K-M) score, and by a more detailed modification of this system. Treg counts were assessed by image analysis quantification. An increase of all TIL subpolulations from precursor lesions toward inSCC was shown by both scoring systems. Treg counts progressively increased from NS to AK and isSCC, but decreased in inSCC. Tregs were more numerous in pT2 and around indolent inSCCs compared to T1 and aggressive subtypes. T-cells and cytotoxic T-cells progressively increase in cutaneous squamous cell carcinogenesis, while Treg counts diminish in inSCC. The K-M score is an appropriate, easily applicable TIL scoring system in cutaneous inSCC. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Distribution of non-aureus staphylococci species in udder quarters with low and high somatic cell count, and clinical mastitis.

PubMed

Condas, Larissa A Z; De Buck, Jeroen; Nobrega, Diego B; Carson, Domonique A; Roy, Jean-Philippe; Keefe, Greg P; DeVries, Trevor J; Middleton, John R; Dufour, Simon; Barkema, Herman W

2017-07-01

The effect of non-aureus staphylococci (NAS) in bovine mammary health is controversial. Overall, NAS intramammary infections (IMI) increase somatic cell count (SCC), with an effect categorized as mild, mostly causing subclinical or mild to moderate clinical mastitis. However, based on recent studies, specific NAS may affect the udder more severely. Some of these apparent discrepancies could be attributed to the large number of species that compose the NAS group. The objectives of this study were to determine (1) the SCC of quarters infected by individual NAS species compared with NAS as a group, culture-negative, and major pathogen-infected quarters; (2) the distribution of NAS species isolated from quarters with low SCC (<200,000 cells/mL) and high SCC (≥200,000 cells/mL), and clinical mastitis; and (3) the prevalence of NAS species across quarters with low and high SCC. A total of 5,507 NAS isolates, 3,561 from low SCC quarters, 1,873 from high SCC quarters, and 73 from clinical mastitis cases, were obtained from the National Cohort of Dairy Farms of the Canadian Bovine Mastitis Research Network. Of quarters with low SCC, high SCC, or clinical mastitis, 7.6, 18.5, and 4.3% were NAS positive, respectively. The effect of NAS IMI on SCC was estimated using mixed-effect linear regression; prevalence of NAS IMI was estimated using Bayesian analyses. Mean SCC of NAS-positive quarters was 70,000 cells/mL, which was higher than culture-negative quarters (32,000 cells/mL) and lower than major pathogen-positive quarters (129,000 to 183,000 cells/mL). Compared with other NAS species, SCC was highest in quarters positive for Staphylococcus capitis, Staphylococcus gallinarum, Staphylococcus hyicus, Staphylococcus agnetis, or Staphylococcus simulans. In NAS-positive quarters, Staphylococcus xylosus (12.6%), Staphylococcus cohnii (3.1%), and Staphylococcus equorum (0.6%) were more frequently isolated from quarters with low SCC than other NAS species, whereas Staphylococcus sciuri (14%) was most frequently isolated from clinical mastitis cases. Finally, in NAS-positive quarters, Staphylococcus chromogenes, S. simulans, Staphylococcus epidermidis, and Staphylococcus haemolyticus were isolated with similar frequency from among low SCC and high SCC quarters and clinical mastitis cases. Staphylococcus chromogenes, S. simulans, S. xylosus, S. haemolyticus, S. epidermidis, S. agnetis, Staphylococcus arlettae, S. capitis, S. gallinarum, S. sciuri, and Staphylococcus warneri were more prevalent in high than in low SCC quarters. Because the NAS are a large, heterogeneous group, considering them as a single group rather than at the species, or even subspecies level, has undoubtedly contributed to apparent discrepancies among studies as to their distribution and importance in IMI and mastitis. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Detecting and targeting mesenchymal-like subpopulations within squamous cell carcinomas

PubMed Central

Montone, Kathleen T; Wang, Li-Ping; Gimotty, Phyllis A; Hammond, Rachel; Diehl, J Alan; Rustgi, Anil K; Lee, John T; Rasanen, Kati; Weinstein, Gregory S

2011-01-01

Curative eradication of all cells within carcinomas is seldom achievable with chemotherapy alone. This limitation may be partially attributable to tumor cell subpopulations with intrinsic resistance to current drugs. Within squamous cell carcinoma (SCC) cell lines, we previously characterized a subpopulation of mesenchymal-like cells displaying phenotypic plasticity and increased resistance to both cytotoxic and targeted agents. These mesenchymal-like (Ecad-lo) cells are separable from epithelial-like (Ecad-hi) cells based on loss of surface E-cadherin and expression of vimentin. Despite their long-term plasticity, both Ecad-lo and Ecad-hi subsets in short-term culture maintained nearly uniform phenotypes after purification. This stability allowed testing of segregated subpopulations for relative sensitivity to the cytotoxic agent cisplatin in comparison to salinomycin, a compound with reported activity against CD44+CD24− stem-like cells in breast carcinomas. Salinomycin showed comparable efficacy against both Ecad-hi and Ecad-lo cells in contrast to cisplatin, which selectively depleted Ecad-hi cells. An in vivo correlate of these mesenchymal-like Ecad-lo cells was identified by immunohistochemical detection of vimentin-positive malignant subsets across a part of direct tumor xenografts (DTXs) of advanced stage SCC patient samples. Cisplatin treatment of mice with established DTXs caused enrichment of vimentin-positive malignant cells in residual tumors, but salinomycin depleted the same subpopulation. These results demonstrate that mesenchymal-like SCC cells, which resist current chemotherapies, respond to a treatment strategy developed against a stem-like subset in breast carcinoma. Further, they provide evidence of mesenchymal-like subsets being well-represented across advanced stage SCCs, suggesting that intrinsic drug resistance in this subpopulation has high clinical relevance. PMID:21558812

Detecting and targeting mesenchymal-like subpopulations within squamous cell carcinomas.

PubMed

Basu, Devraj; Montone, Kathleen T; Wang, Li-Ping; Gimotty, Phyllis A; Hammond, Rachel; Diehl, J Alan; Rustgi, Anil K; Lee, John T; Rasanen, Kati; Weinstein, Gregory S; Herlyn, Meenhard

2011-06-15

Curative eradication of all cells within carcinomas is seldom achievable with chemotherapy alone. This limitation may be partially attributable to tumor cell subpopulations with intrinsic resistance to current drugs. Within squamous cell carcinoma (SCC) cell lines, we previously characterized a subpopulation of mesenchymal-like cells displaying phenotypic plasticity and increased resistance to both cytotoxic and targeted agents. These mesenchymal-like (Ecad-lo) cells are separable from epithelial-like (Ecad-hi) cells based on loss of surface E-cadherin and expression of vimentin. Despite their long-term plasticity, both Ecad-lo and Ecad-hi subsets in short-term culture maintained nearly uniform phenotypes after purification. This stability allowed testing of segregated subpopulations for relative sensitivity to the cytotoxic agent cisplatin in comparison to salinomycin, a compound with reported activity against CD44(+)CD24(-) stem-like cells in breast carcinomas. Salinomycin showed comparable efficacy against both Ecad-hi and Ecad-lo cells in contrast to cisplatin, which selectively depleted Ecad-hi cells. An in vivo correlate of these mesenchymal-like Ecad-lo cells was identified by immunohistochemical detection of vimentin-positive malignant subsets across a part of direct tumor xenografts (DTXs) of advanced stage SCC patient samples. Cisplatin treatment of mice with established DTXs caused enrichment of vimentin-positive malignant cells in residual tumors, but salinomycin depleted the same subpopulation. These results demonstrate that mesenchymal-like SCC cells, which resist current chemotherapies, respond to a treatment strategy developed against a stem-like subset in breast carcinoma. Further, they provide evidence of mesenchymal-like subsets being well-represented across advanced stage SCCs, suggesting that intrinsic drug resistance in this subpopulation has high clinical relevance.

Diagnostic value of CD10 and Bcl2 expression in distinguishing cutaneous basal cell carcinoma from squamous cell carcinoma and seborrheic keratosis.

PubMed

Gaballah, Mohammad A; Ahmed, Rehab-Allah

2015-12-01

The distinction between cutaneous basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and seborrheic keratosis (SK), which are common entities in clinical practice, can be difficult clinically and histologically. CD10 and Bcl2 antigens are important factors in tumor growth, survival and spread. The aim of the present study is to define the frequency of CD10 and Bcl2 expression in such cutaneous tumors and its relation to the clinicopathological characteristics as well as their possible diagnostic utility. CD10 and Bcl2 immunohistochemistry was performed on 30 BCC, 20 SCC and 15 SK. 93.3% of SK cases and 53.3% of BCC cases showed significant expression of CD10 in tumor cells when compared either with each other or with SCC cases (100% negative). Stromal CD10 expression was positive in 50% of BCC cases and 75% of SCC cases. Stromal CD10 expression was significantly higher in high risk BCC and BCC with infiltrating deep margins; furthermore, it showed a significant positive correlation with grade of SCC. A significant inverse correlation between CD10 expression in stromal and tumor cells of BCC was present. Bcl2 was significantly expressed in 93.3% of SK cases and 80% of BCC cases when compared with SCC cases (100% negative). It was found that for distinguishing BCC from SK, only CD10 expression in tumor cells provided a high diagnostic value with positive likelihood ratio (PLR) was 7.00. In addition, CD10 and Bcl2 expression in tumor cells could give convincing diagnostic value to distinguish SCC from SK (PLR=15.00 for each marker). Moreover, for differentiating BCC from SCC, only Bcl2 in the tumor cells could provide a high diagnostic value (PLR=5.5). In conclusion, CD10 and Bcl2 can help in differentiating cutaneous BCC from SK and SCC. The overexpression of CD10 in the stromal cells of SCC and some variants of BCC suggests the invasive properties of such tumors. Copyright © 2015 Elsevier GmbH. All rights reserved.

PDT in squamous cell carcinoma of the skin.

PubMed

Zwiebel, S; Baron, E

2011-12-01

Topical photodynamic therapy (PDT) has been demonstrated to be an effective and safe treatment option for pre-malignancies such as actinic keratoses (AK) and Bowen's disease (BD), with an increasing amount of evidence indicating good long term outcomes. Studies comparing PDT to other options such as cryotherapy and 5-fluorouracil generally demonstrate that PDT is equal to or better than these therapies with respect to patient satisfaction, cosmesis, and efficacy for AK and BD. While there are studies using squamous cell carcinoma (SCC) cells to elucidate the cellular and molecular mechanisms of PDT, this therapy is currently not indicated for treating SCC and surgery is still the first line of therapy. There has been special interest in using PDT to prevent warts, basal cell carcinoma, AK, and BD in solid organ transplant recipients, as these skin lesions are more common in immunosuppressed patients, and trials have been somewhat successful and very promising. Pain remains an obstacle for some patients and techniques such as nerve blocks, cooling packs, and hydration have been attempted to mitigate pain with an overall reduction in pain scores. Optimizing PDT is still a priority and the delivery of pro-drug as well as induction of cellular differentiation are being explored as ways to improve the efficacy of PDT. Perhaps the most interesting use of PDT in treating SCC is the potential for a tumor-specific vaccine, which is currently being developed.

EMMPRIN/CD147 up-regulates urokinase-type plasminogen activator: implications in oral tumor progression

PubMed Central

2012-01-01

Backgrounds An elevated level of EMMPRIN in cancer tissues have been correlated with tumor invasion in numerous cancers including oral cavity and larynx. Although EMMPRIN's effect has been generally attributed to its MMP inducing activity, we have previously demonstrated in breast cancer model that EMMPRIN can also enhance invasion by upregulating uPA. In this study, the role of EMMPRIN in regulating uPA and invasion was investigated in oral squamous cell carcinoma (OSCC) progression. Methods Precancerous and invasive oral tumoral tissues were used as well as the corresponding cell lines, DOK and SCC-9 respectively. The paracrine regulation of uPA by EMMPRIN was investigated by treating culture cells with EMMPRIN-enriched membrane vesicles. UPA expression was analyzed by qPCR and immunostaining and the consequence on the invasion capacity was studied using modified Boyden chamber assay, in the presence or absence of EMMPRIN blocking antibody, the uPA inhibitor amiloride or the MMP inhibitor marimastat. Results OSCC tumors were shown to express more EMMPRIN and uPA compared to dysplastic lesions. The corresponding cell models, SCC-9 and DOK cells, displayed similar expression pattern. In both cell types EMMPRIN upregulated the expression of uPA as well as that of MMP-2 and MMP-9. EMMPRIN treatment led to a significant increase in cell invasion both in the invasive SCC-9 and in the less invasive dysplastic DOK cells, in an MMP and uPA dependent manner. Conclusions Our results suggest that the upregulation of uPA contributes to EMMPRIN's effect in promoting oral tumor invasion. PMID:22443116

EMMPRIN/CD147 up-regulates urokinase-type plasminogen activator: implications in oral tumor progression.

PubMed

Lescaille, Géraldine; Menashi, Suzanne; Cavelier-Balloy, Bénédicte; Khayati, Farah; Quemener, Cathy; Podgorniak, Marie Pierre; Naïmi, Benyoussef; Calvo, Fabien; Lebbe, Céleste; Mourah, Samia

2012-03-23

An elevated level of EMMPRIN in cancer tissues have been correlated with tumor invasion in numerous cancers including oral cavity and larynx. Although EMMPRIN's effect has been generally attributed to its MMP inducing activity, we have previously demonstrated in breast cancer model that EMMPRIN can also enhance invasion by upregulating uPA. In this study, the role of EMMPRIN in regulating uPA and invasion was investigated in oral squamous cell carcinoma (OSCC) progression. Precancerous and invasive oral tumoral tissues were used as well as the corresponding cell lines, DOK and SCC-9 respectively. The paracrine regulation of uPA by EMMPRIN was investigated by treating culture cells with EMMPRIN-enriched membrane vesicles. UPA expression was analyzed by qPCR and immunostaining and the consequence on the invasion capacity was studied using modified Boyden chamber assay, in the presence or absence of EMMPRIN blocking antibody, the uPA inhibitor amiloride or the MMP inhibitor marimastat. OSCC tumors were shown to express more EMMPRIN and uPA compared to dysplastic lesions. The corresponding cell models, SCC-9 and DOK cells, displayed similar expression pattern. In both cell types EMMPRIN upregulated the expression of uPA as well as that of MMP-2 and MMP-9. EMMPRIN treatment led to a significant increase in cell invasion both in the invasive SCC-9 and in the less invasive dysplastic DOK cells, in an MMP and uPA dependent manner. Our results suggest that the upregulation of uPA contributes to EMMPRIN's effect in promoting oral tumor invasion.

Protein expression of MMP-2 and MT1-MMP in actinic keratosis, squamous cell carcinoma of the skin, and basal cell carcinoma.

PubMed

de Oliveira Poswar, Fabiano; de Carvalho Fraga, Carlos Alberto; Gomes, Emisael Stênio Batista; Farias, Lucyana Conceição; Souza, Linton Wallis Figueiredo; Santos, Sérgio Henrique Souza; Gomez, Ricardo Santiago; de-Paula, Alfredo Maurício Batista; Guimarães, André Luiz Sena

2015-02-01

Squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) are 2 skin neoplasms with distinct potentials to invasion and metastasis. Actinic keratosis (AK) is a precursor lesion of SCC. Immunohistochemistry was performed to evaluate the expression of MMP-2 and MT1-MMP in samples of BCC (n = 29), SCC (n = 12), and AK (n = 13). The ratio of positive cells to total cells was used to quantify the staining. Statistical significance was considered under the level P < .05. We found a higher expression of MMP-2 in tumor stroma and parenchyma of SCC as compared to BCC. The expression of this protein was also similar between SCC and its precursor actinic keratosis, and it was higher in the stroma of high-risk BCC when compared to low-risk BCC. MT1-MMP, which is an activator of MMP-2, was similarly expressed in all groups. Our results suggest that MMP-2 expression may contribute to the distinct invasive patterns seen in SCC and BCC. © The Author(s) 2014.

Response of Head and Neck Squamous Cell Carcinoma Cells Carrying PIK3CA Mutations to Select Targeted Therapies

PubMed Central

Wirtz, Eric D; Hoshino, Daisuke; Maldonado, Anthony T; Tyson, Darren R; Weaver, Alissa M

2015-01-01

Importance The PIK3CA mutation is one of the most common mutations in Head and Neck Squamous Cell Carcinoma (HNSCC). Through this research we attempt to elicit the role of oncogene dependence and effects of targeted therapy on this PIK3CA mutation. Objectives 1) To determine the role of oncogene dependence on one of the more common and targetable oncogenes in HNSCC – PIK3CA; 2) To evaluate the consequence of this oncogene on the effectiveness of newly developed targeted therapies. Study Design In vitro study. Setting Academic research laboratory. Participants Cell culture based study assessing the viability of PIK3CA mutated head and neck cell lines when treated with targeted therapy. Exposures PIK3CA mutated head and neck cell lines were treated with 17-AAG, GDC-0941, trametinib, and BEZ-235. Main Outcome and Measures Assessment of cell viability of HNSCC cell lines characterized for PIK3CA mutations or SCC25 cells engineered to express the PIK3CA hotspot mutations E545K or H1047R Results Surprisingly, in engineered cell lines, the hotspot E545K and H1047R mutations conferred decreased, rather than increased, sensitivity as measured by IC50 when treated with the respective HSP90, PI3K, and MEK inhibitors, 17-AAG, GDC-0941, and trametinib, compared to the SCC25 control cell lines. When treated with BEZ-235, H1047R-expressing cell lines showed increased sensitivity to inhibition compared to control while those expressing E545K showed slightly increased sensitivity of unclear significance. Conclusions and Relevance 1) The PIK3CA mutations within our engineered cell model did not lead to enhanced oncogene-dependent cell death when treated with direct inhibition of the PI3K enzyme yet did show increased sensitivity compared to control with dual PI3K/mTOR inhibition. 2) Oncogene addiction to PIK3CA hot spot mutations, if it occurs, is likely to evolve in vivo molecular changes that remain to be identified. Additional study is required to develop new model systems and approaches to determine the role of targeted therapy in the treatment of PI3K-overactive HNSCC tumors. PMID:25855885

Squamous Cell Carcinoma Arising in Hypertrophic Lichen Planus: A Review and Analysis of 38 Cases.

PubMed

Knackstedt, Thomas J; Collins, Lindsey K; Li, Zhongze; Yan, Shaofeng; Samie, Faramarz H

2015-12-01

Hypertrophic lichen planus is a chronic variant of lichen planus with controversial malignant association. To describe and analyze the relationship of squamous cell carcinoma (SCC) and hypertrophic lichen planus. A retrospective chart review of patients with hypertrophic lichen planus and SCC was performed at the authors' institution. Thereafter, scientific databases were searched for articles reporting cases of SCC arising in hypertrophic lichen planus. Patient demographics, immune status, lichen planus features, and SCC data points were extracted for each patient and evaluated. Thirty-eight cases of SCC in hypertrophic lichen planus occurred in 16 women, average age: 61.4, and 22 men, average age: 51.3, after a lag time of 88 days to 40 years. Squamous cell carcinoma was uniformly located on the lower extremity. Men had larger SCC than women (p = .027) and a significantly longer lag time to SCC development (p = .002). Long lag time was associated with a smaller SCC size (p = .032). In the past, hypertrophic lichen planus and SCC have been considered isolated diseases. Based on an increasing number of cases, the association between hypertrophic lichen planus and keratinocyte malignancies warrants surveillance.

Preparation and stability of milk somatic cell reference materials.

PubMed

Di Marzo, Larissa; Wojciechowski, Karen L; Barbano, David M

2016-09-01

Our objectives were to develop a method to produce milk somatic cell count (SCC) reference materials for calibration of electronic somatic cell count (ESCC) using gravity separation and to determine the effect of refrigerated storage (4°C) and freeze-thaw stability of the skim and whole milk SCC reference materials. Whole raw milk was high-temperature short-time pasteurized and split into 2 portions. One portion was gravity separated at 4°C for 22 h and the second portion was centrifugally separated to produce skim milk that was also gravity separated with somatic cells rising to the surface. After 22 h, stock solutions (low SCC skim milk, high SCC skim milk, high SCC whole milk) were prepared and preserved (bronopol). Two experiments were conducted, one to compare the shelf-life of skim and whole milk SCC standards at 4°C and one to determine the effect of freezing and thawing on SCC standards. Both experiments were replicated 3 times. Gravity separation was an effective approach to isolate and concentrate somatic cells from bovine milk and redistribute them in a skim or whole milk matrix to create a set of reference materials with a wider and more uniformly distributed range of SCC than current calibration sets. The liquid SCC reference materials stored using the common industry practice at 4°C were stable (i.e., fit for purpose, no large decrease in SCC) for a 2-wk period, whereas frozen and thawed reference materials may have a much longer useful life. A gradual decrease occurred in residual difference in ESCC (SCC × 1,000/mL) versus original assigned reference SCC over duration of refrigerated storage for both skim and whole milk SCC samples, indicating that milk ESCC of the preserved milks was gradually decreasing during 28 d of storage at 4°C by about 15,000 SCC/mL. No difference in the ESCC for skim milk was detected between refrigerated and frozen storage, whereas for whole milk the ESCC for frozen was lower than refrigerated samples. Future work is needed to determine the time and temperature of longer term frozen storage over which the SCC results are stable. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Enhanced expression of unique gangliosides with GM2-determinant in human uterine cervical carcinoma-derived cell lines.

PubMed

Tanaka, Kyoko; Miyazawa, Masaki; Mikami, Mikio; Aoki, Daisuke; Kiguchi, Kazushige; Iwamori, Masao

2016-10-01

Monoclonal antibody YHD-06 generated by immunization with GM2 reacted with gangliosides with GM2-determinant, i.e., GM2, GalNAc-GM1b and GalNAc-GD1a, among which GalNAc-GD1a was characterized as an antigen of autoimmune peripheral neuropathies including Guillain-Barré syndrome. When glycolipids were examined by TLC-immunostaining with YHD-06 in seven human cervical carcinoma-derived cell lines, GM2 was found in all cell lines, amounting to 15.5 % to 57.5 % of total gangliosides. Whereas GalNAc-GD1a was present in three cell lines, amounting to 5.4-17.5 % of total gangliosides, and GalNAc-GM1b in four cell lines in amounts of less than 2 %. The elevated amounts of gangliosides with GM2 determinant were closely correlated with the relative intensities of gene expression of GalNAc transferase, this being characteristic of cervical carcinoma-derived cells. However, in tissues from patients with several histological types of cervical carcinomas, GM3 was ubiquitously expressed in amounts of more than 66 % of total gangliosides, GM2 was expressed in only five of 15 tissues, and both GalNAc-GM1b and GalNAc-GD1a were not even detected in trace amounts. Since GM1 was detected in all tissues in amounts of less than 0.06 μg/mg dried tissue, all cervical carcinoma tissues were revealed to exhibit GM2 synthesis, indicating that enhanced synthesis of gangliosides with GM2 determinant is a characteristic of cultivated cells in vitro. Similarly, although I(3)SO3-GalCer was not present in the squamous cell carcinoma (SCC) tissues, SCC-derived cells selectively expressed II(3)SO3-LacCer. Since enhanced synthesis of GM2 has been reported in SV-40 virus-transfected fibroblasts, papilloma virus might be involved in the expression of GM2 in cervical carcinoma-derived cells.

IL-6 Inhibition With MEDI5117 Decreases The Fraction of Head and Neck Cancer Stem Cells and Prevents Tumor Recurrence.

PubMed

Finkel, Kelsey A; Warner, Kristy A; Kerk, Samuel; Bradford, Carol R; McLean, Scott A; Prince, Mark E; Zhong, Haihong; Hurt, Elaine M; Hollingsworth, Robert E; Wicha, Max S; Tice, David A; Nör, Jacques E

2016-05-01

Head and neck squamous cell carcinomas (HNSCC) exhibit a small population of uniquely tumorigenic cancer stem cells (CSC) endowed with self-renewal and multipotency. We have recently shown that IL-6 enhances the survival and tumorigenic potential of head and neck cancer stem cells (i.e. ALDH(high)CD44(high) cells). Here, we characterized the effect of therapeutic inhibition of IL-6 with a novel humanized anti-IL-6 antibody (MEDI5117) using three low-passage patient-derived xenograft (PDX) models of HNSCC. We observed that single agent MEDI5117 inhibited the growth of PDX-SCC-M1 tumors (P < .05). This PDX model was generated from a previously untreated HNSCC. In contrast, MEDI5117 was not effective at reducing overall tumor volume for PDX models representing resistant disease (PDX-SCC-M0, PDX-SCC-M11). Low dose MEDI5117 (3 mg/kg) consistently decreased the fraction of cancer stem cells in PDX models of HNSCC when compared to IgG-treated controls, as follows: PDX-SCC-M0 (P < .001), PDX-SCC-M1 (P < .001), PDX-SCC-M11 (P = .04). Interestingly, high dose MEDI5117 (30 mg/kg) decreased the CSC fraction in the PDX-SCC-M11 model (P = .002), but not in PDX-SCC-M0 and PDX-SCC-M1. MEDI5117 mediated a dose-dependent decrease in the number of orospheres generated by ALDH(high)CD44(high) cells cultured in ultra-low attachment plates (P < .05), supporting an inhibitory effect on head and neck cancer stem cells. Notably, single agent MEDI5117 reduced the overall recurrence rate of PDX-SCC-M0, a PDX generated from the local recurrence of human HNSCC. Collectively, these data demonstrate that therapeutic inhibition of IL-6 with low-dose MEDI5117 decreases the fraction of cancer stem cells, and that adjuvant MEDI5117 inhibits recurrence in preclinical models of HNSCC. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Traditional Aboriginal Preparation Alters the Chemical Profile of Carica papaya Leaves and Impacts on Cytotoxicity towards Human Squamous Cell Carcinoma.

PubMed

Nguyen, Thao T; Parat, Marie-Odile; Shaw, Paul N; Hewavitharana, Amitha K; Hodson, Mark P

2016-01-01

Carica papaya leaf decoction, an Australian Aboriginal remedy, has been used widely for its healing capabilities against cancer, with numerous anecdotal reports. In this study we investigated its in vitro cytotoxicity on human squamous cell carcinoma cells followed by metabolomic profiling of Carica papaya leaf decoction and leaf juice/brewed leaf juice to determine the effects imparted by the long heating process typical of the Aboriginal remedy preparation. MTT assay results showed that in comparison with the decoction, the leaf juice not only exhibited a stronger cytotoxic effect on SCC25 cancer cells, but also produced a significant cancer-selective effect as shown by tests on non-cancerous human keratinocyte HaCaT cells. Furthermore, evidence from testing brewed leaf juice on these two cell lines suggested that the brewing process markedly reduced the selective effect of Carica papaya leaf on SCC25 cancer cells. To tentatively identify the compounds that contribute to the distinct selective anticancer activity of leaf juice, an untargeted metabolomic approach employing Ultra High Performance Liquid Chromatography-Quadrupole Time of Flight-Mass Spectrometry followed by multivariate data analysis was applied. Some 90 and 104 peaks in positive and negative mode respectively were selected as discriminatory features from the chemical profile of leaf juice and >1500 putative compound IDs were obtained via database searching. Direct comparison of chromatographic and tandem mass spectral data to available reference compounds confirmed one feature as a match with its proposed authentic standard, namely pheophorbide A. However, despite pheophorbide A exhibiting cytotoxic activity on SCC25 cancer cells, it did not prove to be the compound contributing principally to the selective activity of leaf juice. With promising results suggesting stronger and more selective anticancer effects when compared to the Aboriginal remedy, Carica papaya leaf juice warrants further study to explore its activity on other cancer cell lines, as well as investigation to confirm the identity of compounds contributing to its selective effect, particularly those compounds altered by the long heating process applied during the traditional Aboriginal remedy preparation.

Traditional Aboriginal Preparation Alters the Chemical Profile of Carica papaya Leaves and Impacts on Cytotoxicity towards Human Squamous Cell Carcinoma

PubMed Central

Nguyen, Thao T.; Parat, Marie-Odile; Shaw, Paul N.; Hewavitharana, Amitha K.; Hodson, Mark P.

2016-01-01

Carica papaya leaf decoction, an Australian Aboriginal remedy, has been used widely for its healing capabilities against cancer, with numerous anecdotal reports. In this study we investigated its in vitro cytotoxicity on human squamous cell carcinoma cells followed by metabolomic profiling of Carica papaya leaf decoction and leaf juice/brewed leaf juice to determine the effects imparted by the long heating process typical of the Aboriginal remedy preparation. MTT assay results showed that in comparison with the decoction, the leaf juice not only exhibited a stronger cytotoxic effect on SCC25 cancer cells, but also produced a significant cancer-selective effect as shown by tests on non-cancerous human keratinocyte HaCaT cells. Furthermore, evidence from testing brewed leaf juice on these two cell lines suggested that the brewing process markedly reduced the selective effect of Carica papaya leaf on SCC25 cancer cells. To tentatively identify the compounds that contribute to the distinct selective anticancer activity of leaf juice, an untargeted metabolomic approach employing Ultra High Performance Liquid Chromatography-Quadrupole Time of Flight-Mass Spectrometry followed by multivariate data analysis was applied. Some 90 and 104 peaks in positive and negative mode respectively were selected as discriminatory features from the chemical profile of leaf juice and >1500 putative compound IDs were obtained via database searching. Direct comparison of chromatographic and tandem mass spectral data to available reference compounds confirmed one feature as a match with its proposed authentic standard, namely pheophorbide A. However, despite pheophorbide A exhibiting cytotoxic activity on SCC25 cancer cells, it did not prove to be the compound contributing principally to the selective activity of leaf juice. With promising results suggesting stronger and more selective anticancer effects when compared to the Aboriginal remedy, Carica papaya leaf juice warrants further study to explore its activity on other cancer cell lines, as well as investigation to confirm the identity of compounds contributing to its selective effect, particularly those compounds altered by the long heating process applied during the traditional Aboriginal remedy preparation. PMID:26829042

Danshen extract circumvents drug resistance and represses cell growth in human oral cancer cells.

PubMed

Yang, Cheng-Yu; Hsieh, Cheng-Chih; Lin, Chih-Kung; Lin, Chun-Shu; Peng, Bo; Lin, Gu-Jiun; Sytwu, Huey-Kang; Chang, Wen-Liang; Chen, Yuan-Wu

2017-12-29

Danshen is a common traditional Chinese medicine used to treat neoplastic and chronic inflammatory diseases in China. However, the effects of Danshen on human oral cancer cells remain relatively unknown. This study investigated the antiproliferative effects of a Danshen extract on human oral cancer SAS, SCC25, OEC-M1, and KB drug-resistant cell lines and elucidated the possible underlying mechanism. We investigated the anticancer potential of the Danshen extract in human oral cancer cell lines and an in vivo oral cancer xenograft mouse model. The expression of apoptosis-related molecules was evaluated through Western blotting, and the concentration of in vivo apoptotic markers was measured using immunohistochemical staining. The antitumor effects of 5-fluorouracil and the Danshen extract were compared. Cell proliferation assays revealed that the Danshen extract strongly inhibited oral cancer cell proliferation. Cell morphology studies revealed that the Danshen extract inhibited the growth of SAS, SCC25, and OEC-M1 cells by inducing apoptosis. The Flow cytometric analysis indicated that the Danshen extract induced cell cycle G0/G1 arrest. Immunoblotting analysis for the expression of active caspase-3 and X-linked inhibitor of apoptosis protein indicated that Danshen extract-induced apoptosis in human oral cancer SAS cells was mediated through the caspase pathway. Moreover, the Danshen extract significantly inhibited growth in the SAS xenograft mouse model. Furthermore, the Danshen extract circumvented drug resistance in KB drug-resistant oral cancer cells. The study results suggest that the Danshen extract could be a potential anticancer agent in oral cancer treatment.

Afatinib radiosensitizes head and neck squamous cell carcinoma cells by targeting cancer stem cells

PubMed Central

Macha, Muzafar A; Rachagani, Satyanarayana; Qazi, Asif Khurshid; Jahan, Rahat; Gupta, Suprit; Patel, Anery; Seshacharyulu, Parthasarathy; Lin, Chi; Li, Sicong; Wang, Shuo; Verma, Vivek; Kishida, Shosei; Kishida, Michiko; Nakamura, Norifumi; Kibe, Toshiro; Lydiatt, William M; Smith, Russell B; Ganti, Apar K; Jones, Dwight T; Batra, Surinder K; Jain, Maneesh

2017-01-01

The dismal prognosis of locally advanced and metastatic squamous cell carcinoma of the head and neck (HNSCC) is primarily due to the development of resistance to chemoradiation therapy (CRT). Deregulation of Epidermal Growth Factor Receptor (EGFR) signaling is involved in HNSCC pathogenesis by regulating cell survival, cancer stem cells (CSCs), and resistance to CRT. Here we investigated the radiosensitizing activity of the pan-EGFR inhibitor afatinib in HNSCC in vitro and in vivo. Our results showed strong antiproliferative effects of afatinib in HNSCC SCC1 and SCC10B cells, compared to immortalized normal oral epithelial cells MOE1a and MOE1b. Comparative analysis revealed stronger antitumor effects with afatinib than observed with erlotinib. Furthermore, afatinib enhanced in vitro radiosensitivity of SCC1 and SCC10B cells by inducing mesenchymal to epithelial transition, G1 cell cycle arrest, and the attenuating ionizing radiation (IR)-induced activation of DNA double strand break repair (DSB) ATM/ATR/CHK2/BRCA1 pathway. Our studies also revealed the effect of afatinib on tumor sphere- and colony-forming capabilities of cancer stem cells (CSCs), and decreased IR-induced CSC population in SCC1 and SCC10B cells. Furthermore, we observed that a combination of afatinib with IR significantly reduced SCC1 xenograft tumors (median weight of 168.25 ± 20.85 mg; p = 0.05) compared to afatinib (280.07 ± 20.54 mg) or IR alone (324.91 ± 28.08 mg). Immunohistochemical analysis of SCC1 tumor xenografts demonstrated downregulation of the expression of IR-induced pEGFR1, ALDH1 and upregulation of phosphorylated γH2AX by afatinib. Overall, afatinib reduces tumorigenicity and radiosensitizes HNSCC cells. It holds promise for future clinical development as a novel radiosensitizer by improving CSC eradication. PMID:28423495

Increased expression of enhancer of Zeste Homolog 2 (EZH2) differentiates squamous cell carcinoma from normal skin and actinic keratosis.

PubMed

Xie, Qiang; Wang, Hongbei; Heilman, Edward R; Walsh, Michael G; Haseeb, M A; Gupta, Raavi

2014-01-01

Enhancer of Zeste Homolog 2 (EZH2) is a polycomb group protein that has been shown to be involved in the progression of multiple human cancers including melanoma. The expression of EZH2 in normal skin and in pre-malignant and malignant cutaneous squamous cell carcinoma (SCC) has not been studied. We examined the expression of EZH2 in normal skin, actinic keratosis (AK), SCC in situ, well-differentiated (SCC-WD), moderately-differentiated (SCC-MD) and poorly-differentiated SCC (SCC-PD) to ascertain whether EZH2 expression differentiates these conditions. Immunohistochemical staining for EZH2 was performed on formalin-fixed paraffin-embedded biopsies and a tissue microarray containing normal skin, AK, SCC in situ, and SCC of different grades. In comparison to the normal skin, EZH2 expression in actinic keratosis was increased (p=0.03). Similarly, EZH2 expression in all of the neoplastic conditions studied (SCC in situ, SCC-WD, SCC-MD and SCC-PD) was greatly increased in comparison to both the normal skin and actinic keratosis (p≤0.001). EZH2 expression increases incrementally from normal skin to AK and further to SCC, suggesting a role for EZH2 in the progression and differentiation of SCC. EZH2 expression may be used as a diagnostic marker for differentiating SCC from AK or normal skin.

Medicare claims data reliably identify treatments for basal cell carcinoma and squamous cell carcinoma: a prospective cohort study.

PubMed

Thompson, Bridie S; Olsen, Catherine M; Subramaniam, Padmini; Neale, Rachel E; Whiteman, David C

2016-04-01

To investigate the accuracy of Medical Benefit Schedule (MBS) item numbers to identify treatments for basal cell carcinomas (BCC) and squamous cell carcinomas (SCC). We linked records from QSkin Study participants (n=37,103) to Medicare. We measured the proportion of Medicare claims for primary excision of BCC/SCC that had corresponding claims for histopathology services. In subsets of participants, we estimated the sensitivity and external concordance of MBS item numbers for identifying BCC/SCC diagnoses by comparing against 'gold-standard' histopathology reports. A total of 2,821 (7.6%) participants had 4,830 separate Medicare claims for BCC/SCC excision; almost all (97%) had contemporaneous Medicare claims for histopathology services. Among participants with BCC/SCC confirmed by histology reports, 76% had a corresponding Medicare claim for primary surgical excision of BCC/SCC. External concordance for Medicare claims for primary BCC/SCC excision was 68%, increasing to 97% when diagnoses for intra-epidermal carcinomas and keratoacanthomas were included. MBS item numbers for primary excision of BCC/SCC are reasonably reliable for determining incident cases of keratinocyte skin cancers, but may underestimate incidence by up to 24%. Medicare claims data may have utility in monitoring trends in conditions for which there is no mandatory reporting. © 2015 Public Health Association of Australia.

In vitro assessment of the role of DpC in the treatment of head and neck squamous cell carcinoma.

PubMed

Xu, Ye-Xing; Zeng, Man-Li; Yu, Di; Ren, Jie; Li, Fen; Zheng, Anyuan; Wang, Yong-Ping; Chen, Chen; Tao, Ze-Zhang

2018-05-01

The present study aimed to investigate the antitumor efficacy of di-2-pyridylketone-4-cyclohexyl-4-methyl-3-thiosemicarbazone (DpC) and di-2-pyridylketone-4,4,-dimethyl-3-thiosemicarbazone (Dp44mT) on head and neck squamous cell carcinoma (HNSCC) cells. The proliferation and apoptosis of HNSCC cells treated with the iron chelators DpC and Dp44mT were detected. The mechanism of DpC-induced apoptosis on HNSCC cells was investigated. The human HNSCC cell lines FaDu, Cal-27 and SCC-9 were cultured in vitro and exposed to gradient concentrations of DpC and Dp44mT. A Cell Counting Kit-8 assay was used to detect the viability of FaDu, Cal-27, SCC-9 cells. Double staining with annexin V and propidium iodide was performed for the detection of the proportion of apoptotic FaDu, Cal-27 and SCC-9 cells following treatment. The nuclear damage to Cal-27 cells that were treated with DpC was detected by Hoechst staining. Finally, western blot analysis was used to detect the expression of proteins associated with the DNA damage pathway in Cal-27 cells that were treated with DpC. The CCK-8 assay showed that treatment with DpC and Dp44mT was able to markedly inhibit the viability of FaDu, Cal-27 and SCC-9 cells in a concentration-dependent manner. In comparison to Dp44mT, treatment with DpC exhibited a more effective inhibitory effect on the viability of HNSCC cells. The proportion of apoptotic cells detected by flow cytometry increased in a dose-dependent manner in all cell lines following DpC and Dp44mT treatment, with the proportion of apoptotic HNSCC cells induced by DpC treatment being significantly higher compared with Dp44mT (P<0.05). The results of Hoechst staining revealed that the nuclei of Cal-27 cells exhibited morphological changes in response to DpC treatment, including karyopyknosis and nuclear fragmentation. The expression of DNA damage-associated proteins, including phosphorylated (p)-serine-protein kinase ATM, p-serine/threonine-protein kinase Chk1 (p-Chk-1), p-serine/threonine-protein kinase ATR (p-ATR), p-Chk-2, poly (ADP-ribose) polymerase, p-histone H2AX, breast cancer type 1 susceptibility protein, p-tumor protein P53, increased with increasing concentration of DpC in Cal-27 cells. Treatment with DpC and Dp44mT markedly inhibited cell viability and increased the apoptotic rates in human HNSCC cells in a concentration-dependent manner. DpC exhibited a stronger antitumor effect compared with Dp44mT, potentially inducing the apoptosis of HNSCC cells via the upregulation of DNA damage repair-associated proteins.

Lack of differences in radiation-induced immunogenicity parameters between HPV-positive and HPV-negative human HNSCC cell lines.

PubMed

Schneider, Karolin; Bol, Vanesa; Grégoire, Vincent

2017-09-01

Clinical studies indicate that patients with HPV/p16-associated head & neck squamous cell carcinoma (HNSCC) represent a subgroup with a better prognosis and improved response to conventional radiotherapy. Involvement of immune-based factors has been hypothesized. In the present study, we investigated radiation-induced differences in release of damage associated molecular patterns (DAMPs), cytokines and activation of dendritic cells (DCs) in HPV-positive and negative HNSCC cancer cell lines. Calreticulin (CRT) exposure was detected on cancer cell surface. ATP, HMGB1 and cytokines were measured in culture supernatants. Maturation marker CD83 surface exposure was determined on DCs after co-incubation with irradiated tumor cells. There was no increase in DAMPs and cytokine profiles after radiation treatment and no difference between HPV+ and HPV- cell lines. The HPV/p16-positive SCC90 cells showed a trend for increased total CRT, HMGB1, and number of cytokines compared to all other cell lines. None of the irradiated cancer cell lines could affect DC maturation. Radiation treatment did not increase immunogenicity of HNSCC cell lines assessed by membrane CRT, ATP, HMGB1, cytokines production, and by activation of immature DCs. There was no difference between HPV-positive and HPV-negative cell lines. Copyright © 2017 Elsevier B.V. All rights reserved.

Paranuclear blue inclusions in metastatic undifferentiated small cell carcinoma in the bone marrow.

PubMed

Wittchow, R; Laszewski, M; Walker, W; Dick, F

1992-09-01

Paranuclear blue inclusions (PBIs) are frequently identified within metastatic undifferentiated small cell carcinoma (SCC) cells on air-dried bone marrow aspirates stained with Wright's stain. To determine the sensitivity and specificity of this finding, 116 bone marrow aspirates containing metastatic neoplasms were evaluated for the presence and frequency of PBIs. Bone marrow specimens included 47 cases of metastatic SCC of the lung, 13 cases of large cell lymphoma, 19 cases of neuroblastoma, five cases of small, noncleaved cell lymphoma, seven cases of rhabdomyosarcoma, three cases of Ewing's sarcoma, three cases of other sarcomas, and 19 cases of non-small cell carcinoma (adenocarcinoma). PBIs were identified in 40 of 47 (85%) cases of SCC and their frequency varied from 0 to 24% of tumor cells among different cases. In approximately half the cases of SCC, PBIs were identified in 1 to 4% tumor cells; and in eight cases, PBIs were present in 5% or more of tumor cells. PBIs were also identified in two of seven (29%) cases of rhabdomyosarcoma and one case of malignant peripheral nerve sheath tumor, but they were not seen in Ewing's sarcoma, small non-cleaved cell lymphoma, large cell lymphoma, neuroblastoma, or non-small cell carcinoma. In addition, PBIs were not seen in alcohol-fixed, Papanicolaou-stained cytology specimens containing SCC. Ultrastructurally, PBIs may represent phagocytized nuclear/cellular material. PBIs are a feature of small cell carcinoma on air-dried, cytologic material stained with Romanowsky type stains. Their presence may provide diagnostic information with regard to the differential diagnosis of metastatic SCC in the bone marrow. Future studies evaluating non-bone marrow Wright's stained fine-needle aspiration specimens are needed to determine if PBIs are useful in distinguishing SCC from other poorly differentiated tumors in the cytology laboratory.

A Tetrameric Peptide Derived from Bovine Lactoferricin Exhibits Specific Cytotoxic Effects against Oral Squamous-Cell Carcinoma Cell Lines

PubMed Central

Solarte, Víctor A.; Rosas, Jaiver E.; Rivera, Zuly J.; Arango-Rodríguez, Martha L.; García, Javier E.; Vernot, Jean-Paul

2015-01-01

Several short linear peptides derived from cyclic bovine lactoferricin were synthesized and tested for their cytotoxic effect against the oral cavity squamous-cell carcinoma (OSCC) cell lines CAL27 and SCC15. As a control, an immortalized and nontumorigenic cell line, Het-1A, was used. Linear peptides based on the RRWQWR core sequence showed a moderate cytotoxic effect and specificity towards tumorigenic cells. A tetrameric peptide, LfcinB(20–25)4, containing the RRWQWR motif, exhibited greater cytotoxic activity (>90%) in both OSCC cell lines compared to the linear lactoferricin peptide or the lactoferrin protein. Additionally, this tetrameric peptide showed the highest specificity towards tumorigenic cells among the tested peptides. Interestingly, this effect was very fast, with cell shrinkage, severe damage to cell membrane permeability, and lysis within one hour of treatment. Our results are consistent with a necrotic effect rather than an apoptotic one and suggest that this tetrameric peptide could be considered as a new candidate for the therapeutic treatment of OSCC. PMID:26609531

Nitric oxide metabolite levels in acute vaso-occlusive sickle-cell crisis.

PubMed

Lopez, B L; Barnett, J; Ballas, S K; Christopher, T A; Davis-Moon, L; Ma, X

1996-12-01

1) To measure nitric oxide (NO) metabolite levels in patients presenting to the ED in acute vaso-occlusive sickle-cell crisis (SCC), and 2) to determine whether a relationship exists between NO metabolite levels and pain. A prospective, observational study of patients with documented sickle-cell anemia (SCA), aged > or = 18 years, presenting in typical, acute SCC was conducted in an urban, university teaching hospital. Excluded were those with atypical pain or acute, coexistent disease (as evidenced by fever, tachycardia, tachypnea, or hypotension). Pain scores were measured by a 10-cm visual analog scale (VAS). Blood NO metabolite levels for SCC patients and control subjects (healthy volunteers, n = 9; SCA control subjects not in SCC, n = 10) were determined using an NO-specific chemiluminescence technique that measured plasma nitrite and nitrate, the stable end-products of NO. The acute SCC patients were divided into 3 groups, with the range for the SCC-normal (n = 5) group defined as within 2 SD of the healthy volunteer control patients. The SCC-low patients (n = 21) had NO metabolite levels below this range and the SCC-high (n = 21) patients had levels above this range. The SCA and healthy volunteer control groups had similar NO metabolite levels (25.3 vs 22.6 mumol; p = 0.10). The 3 acute SCC groups had the following mean NO levels: 1) SCC-normal = 21.3 +/- 1.6 mumol; 2) SCC-low = 7.2 +/- 1.1 mumol; and 3) SCC-high = 43.7 +/- 3.5 mumol. The SCC-high NO-level group had significantly lower VAS pain scores when compared with the SCC-low and SCC-normal NO-level groups (6.52 +/- 1.85 cm vs 8.76 +/- 0.83 cm, and 8.62 +/- 1.29 cm, p = 0.02). NO metabolite levels vary in SCC patients. Elevated levels are associated with lower pain scores, while lower levels are associated with higher pain scores, indicating that NO metabolites may potentially represent a marker for compensatory mechanisms in SCC tissue ischemia. Further work is needed to delineate the usefulness of NO metabolites in assessing the severity of SCC.

Differences in survival outcome between oropharyngeal and oral cavity squamous cell carcinoma in relation to HPV status.

PubMed

Lai, Kenneth; Killingsworth, Murray; Matthews, Slade; Caixeiro, Nicole; Evangelista, Carlyn; Wu, Xiao; Wykes, James; Samakeh, Alan; Forstner, Dion; Niles, Navin; Hong, Angela; Lee, Cheok Soon

2017-09-01

This study examined the prognostic significance of human papillomavirus (HPV) in patients with oropharyngeal and oral cavity squamous cell carcinoma (SCC). Tissue microarrays were constructed from oropharyngeal and oral cavity SCC (n = 143). The presence of functional HPV in tumour was determined by combined assessments of p16 immunohistochemistry and HPV in situ hybridisation. Oropharyngeal SCC patients presented with more advanced disease in comparison with oral cavity SCC patients (P = 0.001). HPV is present in 60% and 61% of oropharyngeal and oral cavity SCC patients, respectively. HPV-positive oropharyngeal SCC patients with advanced TNM stages displayed better overall and disease-free survival outcomes than HPV-negative patients (P = 0.022 and 0.046, respectively). Such survival differences were not observed in oral cavity SCC. HPV is common in both oropharyngeal and oral cavity SCC and is associated with better survival outcome in oropharyngeal SCC but not in oral cavity SCC patients. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The role of PD-L1 in the radiation response and prognosis for esophageal squamous cell carcinoma related to IL-6 and T-cell immunosuppression.

PubMed

Chen, Miao-Fen; Chen, Ping-Tsung; Chen, Wen-Cheng; Lu, Ming-Shian; Lin, Paul-Yang; Lee, Kuan Der

2016-02-16

The aim of this study was to assess the significance of programmed cell death 1 ligand 1 (PD-L1) in esophageal squamous cell carcinoma (ESCC) and its association with IL-6 and radiation response. Weretrospectively enrolled 162 patients with ESCC, and examined the correlation between PD-L1 levels and clinical outcomes in esophageal cancer patients. Furthermore, the human esophageal SCC cell line CE81T and TE2 were selected for cellular experiments to investigate the role of PD-L1 in T cell functions and radiation response. Here we demonstrated that PD-L1 expression was significantly higher in esophageal cancer specimens than in non-malignant epithelium. In clinical outcome analysis, this staining of PD-L1 was positively linked to the clinical T4 stage (p=0.004), development of LN metastasis (p=0.012) and higher loco-regional failure rate (p=0.0001). In addition, the frequency of PD-L1 immunoreactivity was significantly higher in IL-6-positive esophageal cancer specimens. When IL-6 signaling was inhibited in vitro, the level of PD-L1 is significantly down-regulated. PD-L1 is a significant predictor for poor treatment response and shorter survival.As demonstrated through in vitro experiments, Irradiation increased PD-L1 expression in human esophageal cancer cells. The inhibition of T cell functions including proliferation and cytotoxicity against tumor cells might be the mechanisms responsible to the role of PD-L1 in radiation response. In conclusion, PD-L1 is important in determining the radiation response and could predict the prognosis of patients with esophageal SCC. Therefore, we suggest inhibition of PD-L1 as a potential strategy for the treatment of esophageal SCC.

Bovine mastitis prevention: humoral and cellular response of dairy cows inoculated with lactic acid bacteria at the dry-off period.

PubMed

Pellegrino, M; Berardo, N; Giraudo, J; Nader-Macías, M E F; Bogni, C

2017-08-24

The use of lactic acid bacteria (LAB) in animal feed, constitute an alternative tool for bovine mastitis prevention. Previously, two LAB strains were isolated from bovine milk and selected for their probiotics properties. So far, immune response of inoculating LAB in bovine udders at dry-off period has not been investigated. The immunoglobulin isotype levels and memory cell proliferation in blood and milk of animals inoculated with Lactobacillus lactis subsp. lactis CRL1655 and Lactobacillus perolens CRL1724 at dry-off period was studied. Ten animals were inoculated intramammarily with 10 6 cells of each LAB (IG) and 2 animals used as control (NIG). Milk and blood samples were taken before inoculation and 1, 2, 4, 6, 12 and 24 h and 7 and 14 days after inoculation. Somatic cell count (SCC) in milk, the presence of bovine mastitis pathogens, the levels of antibodies and lymphocyte proliferation were determined. In the IG, the SCC was <250,000 cells/ml up to 4 h after intramammary inoculation. Six and 12 h after inoculation, the SCC increased up to 600,000 and 2,000,000 cells/ml, respectively. In the NIG, the SCC reached the maximum value 7 days after inoculation. Microbiological analysis showed that all samples were negative for major bovine mastitis pathogens after 24-48 h of incubation. In general, LAB inoculation increased the amount of IgG isotypes in blood and milk, and these antibodies were able to recognise Staphylococcus aureus epitopes. Lymphocytes proliferation was significantly higher in the IG at all time points assayed, following LAB or S. aureus stimulation. The lymphocytes of animals inoculated with LAB do not react in vitro to the presence of S. aureus antigen.. The results showed that probiotic microorganisms could be a natural and effective alternative in the prevention of bovine mastitis at dry-off period and act as immunomodulatory stimulating local and systemic defence lines.

Esophageal adenosquamous carcinoma mimicking acantholytic squamous cell carcinoma

PubMed Central

Matsukuma, Susumu; Takahashi, Oh; Utsumi, Yoshitaka; Tsuda, Masaki; Miyai, Kosuke; Okada, Kenji; Takeo, Hiroaki

2017-01-01

Herein is described a unique case of esophageal cancer mimicking acantholytic squamous cell carcinoma (SCC). The patient succumbed to the disease within one month of diagnosis. Autopsy revealed a 10-cm esophageal tumor, characterized by prominent acantholysis-like areas composed of discohesive cancer cells, along with nested growth of SCC. These discohesive cancer cells focally exhibited pagetoid extension into adjacent esophageal epithelium, comprised ~60% of the esophageal tumor volume and had widely metastasized to the lungs, chest wall, liver, spleen, right adrenal gland, bones and lymph nodes. No metastases of SCC were observed. SCC cells were immunohistochemically positive for keratin 5/6 and E-cadherin and were negative for mucin and carcinoembryonic antigen (CEA). However, the discohesive cancer cells exhibited negativity for keratin 5/6, positivity for mucin and CEA, and diminished or no immunostaining for E-cadherin. Thus, these discohesive cells represented true adenocarcinomatous differentiation rather than acantholytic SCC cells. It was concluded that this tumor was an esophageal adenosquamous carcinoma with ‘pseudo’-acantholytic adenocarcinoma components, which should be considered as a rare but distinctive type of aggressive cancer. PMID:29085501

Wharton's jelly mesenchymal stromal cells have contrasting effects on proliferation and phenotype of cancer stem cells from different subtypes of lung cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vulcano, Francesca, E-mail: francesca.vulcano@iss.it; Milazzo, Luisa, E-mail: luisa.milazzo@iss.it; Ciccarelli, Carmela, E-mail: carmela.ciccarelli@univaq.it

Studies on the role of multipotent mesenchymal stromal cells (MSC) on tumor growth have reported both a tumor promoting and a suppressive effect. The aim of the present study was to determine the effect of MSC isolated from Wharton's jelly of umbilical cord (WJMSC) on lung cancer stem cells (LCSC) derived from human lung tumors: two adenocarcinomas (AC) and two squamous cell carcinomas (SCC). LCSC derived from SCC and AC expressed, to varying extents, the more relevant stem cell markers. The effect of WJMSC on LCSC was investigated in vitro using conditioned medium (WJ-CM): a proliferation increase in AC-LCSC wasmore » observed, with an increase in the ALDH+ and in the CD133+ cell population. By contrast, WJ-CM hampered the growth of SCC-LCSC, with an increase in the pre-G1 phase indicating the induction of apoptosis. Furthermore, the ALDH+ and CD133+ population was also reduced. In vivo, subcutaneous co-transplantation of AC-LCSC/WJMSC generated larger tumors than AC-LCSC alone, characterized by an increased percentage of CD133+ and CD166+ cells. By contrast, co-transplantation of WJMSC and SCC-LCSC did not affect the tumor size. Our results strongly suggest that WJMSC exert, both in vitro and in vivo, contrasting effects on LCSC derived from different lung tumor subtypes. - Highlights: • CM from WJMSC induces apoptosis of SCC-LCSC and reduction of ALDH+ and CD133+ cells. • Specificity of SCC-LCSC inhibition by WJ-CM is proved by the use of a CM from NHDF. • WJ-CM enhance AC-LCSC proliferation and increase CD133+ and ALDH+ cell fractions. • Coinjection of WJMSC with AC-LCSC increase tumor growth with SCC-LCSC has no effect.« less

Acantholytic squamous cell carcinoma is usually associated with hair follicles, not acantholytic actinic keratosis, and is not “high risk”: Diagnosis, management, and clinical outcomes in a series of 115 cases

PubMed Central

Ogawa, Toru; Kiuru, Maija; Konia, Thomas H.; Fung, Maxwell A.

2017-01-01

Background Acantholytic squamous cell carcinoma (aSCC) is regarded as a high-risk variant of cutaneous squamous cell carcinoma (SCC). Acantholytic actinic keratosis (aAK) has been regarded as a precursor risk factor for aSCC. However, supporting evidence is limited. Objective We sought to document clinical features, histologic features, management, and outcomes in a series of aSCC cases. Methods Definitions of aSCC, aAK, and aSCC arising in association with aAK were applied to a consecutive series of aSCC cases. Clinical characteristics and outcomes were obtained from electronic medical records. Results Of 115 aSCC cases (103 patients, mean age 71.8 years), actinic keratosis was present in 23% (27/115) but only 7.8% (9/115) exhibited associated aAK. Ten cases (10/115, 9%) fulfilled strict histologic criteria for follicular SCC as previously defined, but 50 of 115 (43%) of our aSCC cases exhibited predominant involvement of follicular epithelium rather than epidermis. Clinical outcome (median follow-up, 36 months) was available in 106 of 115 (92%). One patient experienced regional extension (parotid), and 1 patient experienced a local recurrence (nose). No disease-related metastases or deaths were documented. Limitations This was a single-institution retrospective study from the United States. Conclusions The presence of acantholysis in cutaneous SCC does not specifically confer aggressive behavior, a finding that may inform clinical practice guidelines. PMID:27889291

Acantholytic squamous cell carcinoma is usually associated with hair follicles, not acantholytic actinic keratosis, and is not "high risk": Diagnosis, management, and clinical outcomes in a series of 115 cases.

PubMed

Ogawa, Toru; Kiuru, Maija; Konia, Thomas H; Fung, Maxwell A

2017-02-01

Acantholytic squamous cell carcinoma (aSCC) is regarded as a high-risk variant of cutaneous squamous cell carcinoma (SCC). Acantholytic actinic keratosis (aAK) has been regarded as a precursor risk factor for aSCC. However, supporting evidence is limited. We sought to document clinical features, histologic features, management, and outcomes in a series of aSCC cases. Definitions of aSCC, aAK, and aSCC arising in association with aAK were applied to a consecutive series of aSCC cases. Clinical characteristics and outcomes were obtained from electronic medical records. Of 115 aSCC cases (103 patients, mean age 71.8 years), actinic keratosis was present in 23% (27/115) but only 7.8% (9/115) exhibited associated aAK. Ten cases (10/115, 9%) fulfilled strict histologic criteria for follicular SCC as previously defined, but 50 of 115 (43%) of our aSCC cases exhibited predominant involvement of follicular epithelium rather than epidermis. Clinical outcome (median follow-up, 36 months) was available in 106 of 115 (92%). One patient experienced regional extension (parotid), and 1 patient experienced a local recurrence (nose). No disease-related metastases or deaths were documented. This was a single-institution retrospective study from the United States. The presence of acantholysis in cutaneous SCC does not specifically confer aggressive behavior, a finding that may inform clinical practice guidelines. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

In vitro and in vivo antitumor effects of chloroquine on oral squamous cell carcinoma

PubMed Central

Jia, Lihua; Wang, Juan; Wu, Tong; Wu, Jinan; Ling, Junqi; Cheng, Bin

2017-01-01

Chloroquine, which is a widely used antimalarial drug, has been reported to exert anticancer activity in some tumor types; however, its potential effects on oral squamous cell carcinoma (OSCC) remain unclear. The present study aimed to explore the effects and possible underlying mechanisms of chloroquine against OSCC. MTT and clonogenic assays were conducted to evaluate the effects of chloroquine on the human OSCC cell lines SCC25 and CAL27. Cell cycle progression and apoptosis were detected using flow cytometry. Autophagy was monitored using microtubule-associated protein 1A/1B-light chain 3 as an autophagosomal marker. In order to determine the in vivo antitumor effects of chloroquine on OSCC, a CAL27 xenograft model was used. The results demonstrated that chloroquine markedly inhibited the proliferation and the colony-forming ability of both OSCC cell lines in a dose- and time-dependent manner in vitro. Chloroquine also disrupted the cell cycle, resulting in the cell cycle arrest of CAL27 and SCC25 cells at G0/G1 phase, via downregulation of cyclin D1. In addition, chloroquine inhibited autophagy, and induced autophagosome and autolysosome accumulation in the cytoplasm, thus interfering with degradation; however, OSCC apoptosis was barely affected by chloroquine. The results of the in vivo study demonstrated that chloroquine effectively inhibited OSCC tumor growth in the CAL27 xenograft model. In conclusion, the present study reported the in vitro and in vivo antitumor effects of chloroquine on OSCC, and the results indicated that chloroquine may be considered a potent therapeutic agent against human OSCC. PMID:28849182

Red blood cell aggregation, aggregate strength and oxygen transport potential of blood are abnormal in both homozygous sickle cell anemia and sickle-hemoglobin C disease.

PubMed

Tripette, Julien; Alexy, Tamas; Hardy-Dessources, Marie-Dominique; Mougenel, Daniele; Beltan, Eric; Chalabi, Tawfik; Chout, Roger; Etienne-Julan, Maryse; Hue, Olivier; Meiselman, Herbert J; Connes, Philippe

2009-08-01

Recent evidence suggests that red blood cell aggregation and the ratio of hematocrit to blood viscosity (HVR), an index of the oxygen transport potential of blood, might considerably modulate blood flow dynamics in the microcirculation. It thus seems likely that these factors could play a role in sickle cell disease. We compared red blood cell aggregation characteristics, blood viscosity and HVR at different shear rates between sickle cell anemia and sickle cell hemoglobin C disease (SCC) patients, sickle cell trait carriers (AS) and control individuals (AA). Blood viscosity determined at high shear rate was lower in sickle cell anemia (n=21) than in AA (n=52), AS (n=33) or SCC (n=21), and was markedly increased in both SCC and AS. Despite differences in blood viscosity, both sickle cell anemia and SCC had similar low HVR values compared to both AA and AS. Sickle cell anemia (n=21) and SCC (n=19) subjects had a lower red blood cell aggregation index and longer time for red blood cell aggregates formation than AA (n=16) and AS (n=15), and a 2 to 3 fold greater shear rate required to disperse red blood cell aggregates. The low HVR levels found in sickle cell anemia and SCC indicates a comparable low oxygen transport potential of blood in both genotypes. Red blood cell aggregation properties are likely to be involved in the pathophysiology of sickle cell disease: the increased shear forces needed to disperse red blood cell aggregates may disturb blood flow, especially at the microcirculatory level, since red blood cell are only able to pass through narrow capillaries as single cells rather than as aggregates.

Cross-species identification of genomic drivers of squamous cell carcinoma development across preneoplastic intermediates

PubMed Central

Chitsazzadeh, Vida; Coarfa, Cristian; Drummond, Jennifer A.; Nguyen, Tri; Joseph, Aaron; Chilukuri, Suneel; Charpiot, Elizabeth; Adelmann, Charles H.; Ching, Grace; Nguyen, Tran N.; Nicholas, Courtney; Thomas, Valencia D.; Migden, Michael; MacFarlane, Deborah; Thompson, Erika; Shen, Jianjun; Takata, Yoko; McNiece, Kayla; Polansky, Maxim A.; Abbas, Hussein A.; Rajapakshe, Kimal; Gower, Adam; Spira, Avrum; Covington, Kyle R.; Xiao, Weimin; Gunaratne, Preethi; Pickering, Curtis; Frederick, Mitchell; Myers, Jeffrey N.; Shen, Li; Yao, Hui; Su, Xiaoping; Rapini, Ronald P.; Wheeler, David A.; Hawk, Ernest T.; Flores, Elsa R.; Tsai, Kenneth Y.

2016-01-01

Cutaneous squamous cell carcinoma (cuSCC) comprises 15–20% of all skin cancers, accounting for over 700,000 cases in USA annually. Most cuSCC arise in association with a distinct precancerous lesion, the actinic keratosis (AK). To identify potential targets for molecularly targeted chemoprevention, here we perform integrated cross-species genomic analysis of cuSCC development through the preneoplastic AK stage using matched human samples and a solar ultraviolet radiation-driven Hairless mouse model. We identify the major transcriptional drivers of this progression sequence, showing that the key genomic changes in cuSCC development occur in the normal skin to AK transition. Our data validate the use of this ultraviolet radiation-driven mouse cuSCC model for cross-species analysis and demonstrate that cuSCC bears deep molecular similarities to multiple carcinogen-driven SCCs from diverse sites, suggesting that cuSCC may serve as an effective, accessible model for multiple SCC types and that common treatment and prevention strategies may be feasible. PMID:27574101

Squamous cell carcinoma of the bladder mimicking interstitial cystitis and voiding dysfunction.

PubMed

Prudnick, Colton; Morley, Chad; Shapiro, Robert; Zaslau, Stanley

2013-01-01

Squamous cell carcinoma (SCC) of the bladder is a relatively uncommon cause of bladder cancer accounting for <5% of bladder tumors in the western countries. SCC has a slight male predominance and tends to occur in the seventh decade of life. The main presenting symptom of SCC is hematuria, and development of this tumor in the western world is associated most closely with chronic indwelling catheters and spinal cord injuries. A 39-year-old Caucasian female presented with bladder and lower abdominal pain, urinary frequency, and nocturia which was originally believed to be interstitial cystitis (IC) but was later diagnosed as SCC of the bladder. Presentation of SCC without hematuria is an uncommon presentation, but the absence of this symptom should not lead a practitioner to exclude the diagnosis of SCC. This case is being reported in an attempt to explain the delay and difficulty of diagnosis. Background on the risk factors for SCC of the bladder and the typical presenting symptoms of bladder SCC and IC are also reviewed.

Invited review: Low milk somatic cell count and susceptibility to mastitis.

PubMed

Rainard, P; Foucras, G; Boichard, D; Rupp, R

2018-05-23

An enduring controversy exists about low milk cell counts and susceptibility to mastitis. The concentration of milk leukocytes, or somatic cell count (SCC), is a well-established direct indicator of mammary gland inflammation that is highly correlated with the presence of a mammary infection. The SCC is also used as a trait for the selection of dairy ruminants less prone to mastitis. As selection programs favor animals with less SCC, and as milk cells contribute to the defense of the mammary gland, the idea that susceptibility to mastitis could possibly be increased in the long term has been put forward and is still widely debated. Epidemiological and experimental studies aimed at relating SCC to susceptibility to mastitis have yielded results that seem contradictory at first sight. Nevertheless, by taking into account the immunobiology of milk and mammary tissue cells and their role in the defense against infection, along with recent studies on SCC-based divergent selection of animals, the issue can be settled. Apparent SCC-linked susceptibility to mastitis is a phenotypic trait that may be linked to immunomodulation but not to selection. Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Curcumin inhibits oral squamous cell carcinoma SCC-9 cells proliferation by regulating miR-9 expression

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xiao, Can; Department of Stomatology, The First Affiliated Hospital of Soochow University, Suzhou 215006; Wang, Lili

Highlights: • miR-9 expression level was significantly decreased in OSCC tissues. • Curcumin significantly inhibited SCC-9 cells proliferation. • miR-9 mediates the inhibition of SCC-9 proliferation by curcumin. • Curcumin suppresses Wnt/β-catenin signaling in SCC-9 cells. • miR-9 mediates the suppression of Wnt/β-catenin signaling by curcumin. - Abstract: Curcumin, a phytochemical derived from the rhizome of Curcuma longa, has shown anticancer effects against a variety of tumors. In the present study, we investigated the effects of curcumin on the miR-9 expression in oral squamous cell carcinoma (OSCC) and explored the potential relationships between miR-9 and Wnt/β-catenin pathway in curcumin-mediated OSCCmore » inhibition in vitro. As the results shown, the expression levels of miR-9 were significantly lower in clinical OSCC specimens than those in the adjacent non-tumor tissues. Furthermore, our results indicated that curcumin inhibited OSCC cells (SCC-9 cells) proliferation through up-regulating miR-9 expression, and suppressing Wnt/β-catenin signaling by increasing the expression levels of the GSK-3β, phosphorylated GSK-3β and β-catenin, and decreasing the cyclin D1 level. Additionally, the up-regulation of miR-9 by curcumin in SCC-9 cells was significantly inhibited by delivering anti-miR-9 but not control oligonucleotides. Downregulation of miR-9 by anti-miR-9 not only attenuated the growth-suppressive effects of curcumin on SCC-9 cells, but also re-activated Wnt/β-catenin signaling that was inhibited by curcumin. Therefore, our findings would provide a new insight into the use of curcumin against OSCC in future.« less

Evolution of taste and solitary chemoreceptor cell systems.

PubMed

Finger, T E

1997-01-01

Vertebrates possess four distinct chemosensory systems distinguishable on the basis of structure, innervation and utilization: olfaction, taste, solitary chemoreceptor cells (SCC) and the common chemical sense (free nerve endings). Of these, taste and the SCC sense rely on secondary receptor cells situated in the epidermis and synapsing on sensory nerve fibers innervating them near their base. The SCC sense occurs in anamniote aquatic craniates, including hagfish, and may be used for feeding or predator avoidance. The sense of taste occurs only in vertebrates and is always utilized for feeding. The SCC system achieves a high degree of specialization in two teleosts: sea robins (Prionotus) and rocklings (Ciliata). In sea robins, SCCs are abundant on the three anterior fin rays of the pectoral fin which are free of fin webbing and are used in active exploration of the substrate. Behavioral and physiological studies show that this SCC system responds to feeding cues and drives feeding behavior. It is connected centrally like a somatosensory system. In contrast, the specialized SCC system of rocklings occurs on the anterior dorsal fin which actively samples the surrounding water. This system responds to mucus substances and may serve as a predator detector. The SCC system in rocklings is connected centrally like a gustatory system. Taste buds contain multiple receptor cell types, including a serotonergic Merkel-like cell. Taste receptor cells respond to nutritionally relevant substances. Due to similarities between SCCs and one type of taste receptor cell, the suggestion is made that taste buds may be compound sensory organs that include some cells related to SCCs and others related to cutaneous Merkel cells. The lack of taste buds in hagfish and their presence in all vertebrates may indicate that the phylogenetic development of taste buds coincided with the elaboration of head structures at the craniate-vertebrate transition.

Candida albicans triggers interleukin-8 secretion by oral epithelial cells.

PubMed

Dongari-Bagtzoglou, A; Kashleva, H

2003-04-01

Oropharyngeal candidiasis is a frequent opportunistic infection associated with immunocompromised hosts. Candida albicans is the principal species responsible for this infection. Production of interleukin-8 (IL-8), by oral epithelial cells can be expected to play a major role in the recruitment and activation of professional phagocytes at the infected site. The purpose of this study was to determine whether C. albicans triggers secretion of IL-8 by oral epithelial cells in vitro and investigate mechanisms of host cell-fungal interactions that trigger such responses. Oral epithelial cell lines (SCC4, SCC15, and OKF6/TERT-2) as well as primary gingival epithelial cells were used. Epithelial cells were cocultured with C. albicans, strains SC5314, ATCC28366 or ATCC32077, for 24-48 hr, and supernatants were analyzed for IL-8 content by ELISA. A germination-deficient mutant (efg1/efg1 cph1/cph1), otherwise isogenic to strain SC5314, was used to assess the requirement for germination in triggering IL-8 responses. In order to ascertain whether direct contact of yeast with host cells is required to trigger cytokine production, epithelial cells were separated from yeast using cell culture inserts. To test whether IL-8 secretion is dependent on IL-1alpha activity, epithelial cells were challenged with viable C. albicans in the presence or absence of neutralizing anti-IL-1alpha antibody or IL-1ra, and IL-8 secretion was measured in the supernatants. All cell lines and primary cultures responded to C. albicans with an increase in IL-8 secretion. IL-8 responses were contact-dependent, strain-specific, required yeast viability and germination into hyphae, and were in part autoregulated by IL-1alpha. Copyright 2003 Elsevier Science Ltd.

Evaluation of milk cathelicidin for detection of bovine mastitis.

PubMed

Addis, M F; Tedde, V; Puggioni, G M G; Pisanu, S; Casula, A; Locatelli, C; Rota, N; Bronzo, V; Moroni, P; Uzzau, S

2016-10-01

Mastitis due to intramammary infection is one of the most economically relevant diseases in dairy cows, causing reductions in milk quality and quantity. Currently, mastitis monitoring is based on somatic cell count (SCC) and bacteriologic culture (BC) of milk. Nevertheless, inflammation-specific protein markers might provide more sensitive and reliable assays, enabling immunoassay-based screening strategies. Cathelicidin is an inflammatory protein released in milk that has recently demonstrated fair reliability and diagnostic potential for ewe mastitis. To assess its performance in cows, 531 quarter milk samples from 2 herds were tested using cathelicidin ELISA, SCC, and BC. We found that 29.0% of samples were positive for cathelicidin, 18.8% had SCC >200,000 cells/mL, and 13.7% were BC-positive. Cathelicidin showed a strong positive correlation with SCC as demonstrated by receiver operating characteristics curve analysis and by the clustering of cathelicidin-negative and cathelicidin-positive samples in association with low and high SCC values, respectively. For evaluating the diagnostic performance of a novel test, BC cannot be considered a reliable gold standard for true disease status because of its known limitations. Therefore, we assessed the sensitivity (Se) and specificity (Sp) of the milk cathelicidin ELISA using a latent class analysis approach together with BC and SCC by considering different diagnostic thresholds to identify the preferred Se/Sp combination. We modeled conditional dependence of cathelicidin and SCC to account for their close association. The cathelicidin ELISA showed higher Se than SCC and BC for almost all threshold combinations. In fact, at the best-performing threshold combination, the Se of cathelicidin was 80.6%, 6.2 percentage points higher than that of SCC >200,000 cells/mL (74.4%) and similar to that of SCC >100,000 cells/mL (80.2%). Most importantly, this Se was obtained with a loss in Sp of only 1.4 percentage points compared with SCC >200,000 cells/mL (94.9% Sp for cathelicidin vs. 96.3% for SCC >200,000). The limited Se of BC (38.8%) was also confirmed in this study, and BC showed a slightly lower Sp than both cathelicidin and SCC for most of threshold combinations. This study confirmed that cathelicidin is released in the milk of cows with mastitis and that its presence is highly correlated with SCC. The measurement of cathelicidin by ELISA may hold significant potential for improving the sensitivity of mastitis detection in dairy cows while maintaining high specificity. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Rectal squamous cell carcinoma in immunosuppressed populations: is this a distinct entity from anal cancer?

PubMed Central

COGHILL, Anna E.; SHIELS, Meredith S.; RYCROFT, Randi K.; COPELAND, Glenn; FINCH, Jack L.; HAKENEWERTH, Anne M.; PAWLISH, Karen S.; ENGELS, Eric A.

2015-01-01

Objective Squamous cell carcinoma (SCC) of the rectum is rare, but as with anal cancer, risk may be increased among immunosuppressed individuals. We assessed risk of rectal SCC in HIV-infected people. Design Population-based registry Methods We utilized the HIV/AIDS Cancer Match, a linkage of US HIV and cancer registries (1991–2010), to ascertain cases of anal SCC, rectal SCC, rectal non-SCC, and colon non-SCC. We compared risk in HIV-infected persons to the general population using standardized incidence ratios (SIRs) and evaluated risk factors using Poisson regression. We reviewed cancer registry case notes to confirm site and histology for a subset of cases. Results HIV-infected persons had an excess risk of rectal SCC compared to the general population (SIR=28.9; 95%CI 23.2–35.6), similar to the increase for anal SCC (SIR=37.3). Excess rectal SCC risk was most pronounced among HIV-infected men who have sex with men (MSM, SIR=61.2). Risk was not elevated for rectal non-SCC (SIR=0.88) or colon non-SCC (SIR=0.63). Individuals diagnosed with AIDS had higher rectal SCC rates than those with HIV-only (incidence rate ratio=1.86; 95%CI 1.04–3.31). Based on available information, one-third of rectal SCCs were determined to be misclassified anal cancer. Conclusions HIV-infected individuals, especially with advanced immunosuppression, appear to have substantially elevated risk for rectal SCC. As for anal SCC, rectal SCC risk was highest in MSM, pointing to involvement of a sexually transmitted infection such as human papillomavirus. Site misclassification was present, and detailed information on tumor location is needed to prove that rectal SCC is a distinct entity. PMID:26372482

Advanced cutaneous squamous cell carcinoma: A retrospective analysis of patient profiles and treatment patterns-Results of a non-interventional study of the DeCOG.

PubMed

Hillen, Uwe; Leiter, Ulrike; Haase, Sylvie; Kaufmann, Roland; Becker, Jürgen; Gutzmer, Ralf; Terheyden, Patrick; Krause-Bergmann, Albrecht; Schulze, Hans-Joachim; Hassel, Jessica; Lahner, Nina; Wollina, Uwe; Ziller, Fabian; Utikal, Jochen; Hafner, Christine; Ulrich, Jens; Machens, Hans-Günther; Weishaupt, Carsten; Hauschild, Axel; Mohr, Peter; Pföhler, Claudia; Maurer, Jan; Wolff, Patrick; Windemuth-Kieselbach, Christine; Schadendorf, Dirk; Livingstone, Elisabeth

2018-04-14

Advanced cutaneous squamous cell carcinoma (aSCC) is an area of unmet medical need and no treatment standards are established. Recently, an anti-PD-1 inhibitor received FDA breakthrough therapy designation. The aim of the study was to describe the clinical course, therapeutic management and prognosis of aSCC under real-life conditions. In a retrospective study performed in 24 German and Austrian hospitals and doctor's offices, patient and tumour characteristics of patients diagnosed with aSCC between January 1, 2010 and December 31, 2011 and their disease course was documented. Advanced SCC comprised either locally advanced SCCs (laSCC) or metastatic SCCs (mSCC) with any kind of metastatic spread. Data of 190 patients with aSCC were analysed. Median age at time of diagnosis of aSCC was 78 years. LaSCC was diagnosed in 76 patients (40%), 114 patients (60%) had mSCC. Once diagnosed with laSCC, most patients (59%) did not receive any therapy, whereas in 92% of mSCC patients at least one type of therapy was performed. Only 32 patients (29 mSCC, 3 laSCC) received systemic antitumour therapies, mostly EGFR inhibitor-based regimens. Mean duration of response was short (17-months laSCC patients, 3-months mSCC patients). Only 2 patients achieved a complete response, 27% had a partial response, 43% disease stabilisation. At diagnosis of aSCC, ECOG status was 0-1 in most patients. Non-malignant comorbidities influenced the decision on SCC-specific therapy in 39 patients (21%). Our data show the high medical need for efficient and tolerable antitumour therapies and demonstrate that despite older age and comorbidities, most patients can be expected to be fit for treatment. This study provides a historical context for emerging aSCC treatments. Copyright © 2018 Elsevier Ltd. All rights reserved.

A novel extracellular drug conjugate significantly inhibits head and neck squamous cell carcinoma

PubMed Central

Sweeny, Larissa; Hartman, Yolanda E.; Zinn, Kurt R.; Prudent, James R.; Marshall, David J.; Shekhani, Mohammed S.; Rosenthal, Eben L.

2014-01-01

Objectives Despite advances in treatment modalities, head and neck squamous cell carcinoma (HNSCC) remains a challenge to treat with poor survival and high morbidity, necessitating a therapy with greater efficacy. EDC22 is an extracellular drug conjugate of the monoclonal antibody targeting CD147 (glycoprotein highly expressed on HNSCC cells) linked with a small drug molecule inhibitor of Na, K-ATPase. In this study, EDC22’s potential as a treatment modality for HNSCC was performed. Materials and methods HNSCC cell lines (FADU, OSC-19, Cal27, SCC-1) were cultured in vitro and proliferation and cell viability were assessed following treatment with a range of concentrations of EDC22 (0.25–5.00 μg/mL). Mice bearing HNSCC xenografts (OSC-19, SCC-1) were treated with either EDC22 (3–10 mg/kg), anti-CD147 monoclonal antibody, cisplatin (1 mg/kg) or radiation therapy (2 Gy/week) monotherapy or in combination. Results In vitro, treatment with minimal concentration of EDC22 (0.25 μg/mL) significantly decreased cellular proliferation and cell viability (p < 0.0001). In vivo, systemic treatment with EDC22 significantly decreased primary tumor growth rate in both an orthotopic mouse model (OSC-19) and a flank tumor mouse model (SCC-1) (p < 0.05). In addition, EDC22 therapy resulted in a greater reduction in tumor growth in vivo compared to radiation monotherapy (p < 0.05) and a similar reduction in tumor growth compared to cisplatin monotherapy. Combination therapy provided no significant further reduction in tumor growth relative to EDC22 monotherapy. Conclusion EDC22 is a potent inhibitor of HNSCC cell proliferation in vitro and in vivo, warranting further investigations of its clinical potential in the treatment of HNSCC. PMID:23920309

Basaloid Squamous Cell Carcinoma of the Anus Revisited.

PubMed

Graham, Rondell P; Arnold, Christina A; Naini, Bita V; Lam-Himlin, Dora M

2016-03-01

Basaloid squamous cell carcinoma (SCC) of the anus, previously called cloacogenic carcinoma, is a subtype of SCC. There are very few data on the morphologic variation within basaloid SCC of the anus, which may contribute to misdiagnosis. We retrospectively evaluated cases originally diagnosed as basaloid SCC for histologic characterization. We retrieved and reviewed cases of basaloid SCC from 1994 to 2013. Ten (27%) cases were reclassified after review, including basal cell carcinoma (n=6), melanoma (n=2), and neuroendocrine carcinoma (n=2). The final group of basaloid SCC (n=27) showed a female predominance (median age=60 y; range, 42 to 92 y). Morphologically, basaloid SCC could be categorized into 4 groups: transitional carcinoma like (n=10), basaloid with peripheral palisade (n=13), adenoid cystic carcinoma like (n=3), and mucinous microcystic (n=1). In 19 cases the histologic patterns were pure and were mixed in the remainder. CK5/6, p16, and high-risk HPV were positive in all cases (n=27). SOX2 was positive in 18/22 cases. Clinical follow-up was available on 60% of cases; 9 patients (53%) developed local recurrence or metastasis, and 5 (29%) died of disease. Basaloid SCC of the anus is characterized by 4 major histologic patterns and is consistently HPV driven.

Family history of skin cancer is associated with increased risk of cutaneous squamous cell carcinoma.

PubMed

Asgari, Maryam M; Warton, E Margaret; Whittemore, Alice S

2015-04-01

The contribution of family history to cutaneous squamous cell carcinoma (SCC) risk has not been systematically quantified. To examine the association between self-reported family history of skin cancer and SCC risk. Cases (n = 415) with a pathology-verified SCC and 415 age-, gender-, and race-matched controls were identified within a large integrated health care delivery system. Family history and skin cancer risk factors were ascertained by survey. Odds ratios (ORs) for associations of SCC with family history of skin cancer were estimated using conditional logistic regression adjusted for environmental and innate SCC risk factors. Any known family history of skin cancer was associated with a four-fold higher risk of SCC, adjusting for known environmental and innate SCC risk factors (OR, 4.0; confidence interval [CI]: 2.5-6.5). An unknown family history of skin cancer showed similar risk for SCC (OR, 3.9; CI: 2.4-6.5). In models including skin cancer type, the strongest association was for family history of basal cell carcinoma (OR, 9.8; CI: 2.6-36.8) and for multiple skin cancer types (OR, 10.5; CI: 3.7-29.6). Family history of skin cancer is an important independent risk factor for cutaneous SCCs.

Human papillomavirus-associated increase in p16INK4A expression in penile lichen sclerosus and squamous cell carcinoma.

PubMed

Prowse, D M; Ktori, E N; Chandrasekaran, D; Prapa, A; Baithun, S

2008-02-01

Human papillomaviruses (HPVs) are sexually transmitted human carcinogens that may play a role in the oncogenesis of penile cancer. To investigate the role of HPV infection and expression of the tumour suppressor protein p16INK4A in the pathogenesis of penile cancer. By means of polymerase chain reaction amplification and reverse hybridization line probe assay to detect HPV infection, and immunohistochemical staining for p16INK4A and Ki67, we analysed 26 penile squamous cell carcinomas (SCCs) and 20 independent penile lichen sclerosus (LS) lesions from 46 patients. HPV DNA was found in 54% of penile SCCs and 33% of penile LS cases in single and multiple infections. High-risk HPV 16 was the predominant HPV type detected. No relationship between Ki67 expression and HPV infection was observed. Strong immunostaining for p16INK4A correlated with HPV 16/18 infection in both penile LS and penile SCC. In our penile SCC series the cancer margins were also associated with penile LS in 13 of 26 lesions, and HPV was detected in seven of the 13 SCC cases associated with LS and in six of the 11 SCC lesions not involving LS. Our study shows a high prevalence of HPV 16 and p16INK4A expression in penile lesions, consistent with an active role for HPV in interfering with the retinoblastoma pathway. High-risk HPV infection could be involved in the tumorigenic process in 50% of penile cancers, and the use of prophylactic HPV vaccines has the potential to prevent these cancers.

Using dairy herd improvement records and clinical mastitis history to identify subclinical mastitis infections at dry-off.

PubMed

Torres, Audrey H; Rajala-Schultz, Päivi J; Degraves, Fred J; Hoblet, Kent H

2008-05-01

Interest in selective dry cow therapy (SDCT) has been increasing owing to concerns over development of antimicrobial resistance. Implementation of SDCT, however, requires a quick and cost-effective on-farm method for identifying cows for treatment and cows that can be left without treatment. The objective of the present study was to evaluate the use of clinical mastitis (CM) history and somatic cell counts (SCC) from monthly Dairy Herd Improvement (DHI) records in identification of infected and uninfected cows at dry-off. A total of 647 Holstein cows were classified as uninfected or infected at dry-off based on CM history and varying number of monthly SCC records (with three different SCC cut-offs). Cows were considered uninfected based on the following criteria: (1) SCC <100,000 cells/ml and no CM during the lactation; (2) SCC <200,000 cells/ml and no CM during the lactation; (3) as criterion two, but additionally a cow was also considered uninfected if it experienced a case of CM during the first 3 months of the lactation and the SCC was <100,000 cells/ml for the rest of the lactation; (4) SCC <300,000 cells/ml and no CM during the lactation; otherwise they were considered infected. Infected and uninfected cows at dry-off were most efficiently identified using three months' SCC records with a threshold of 200,000 cells/ml for cows without CM during the lactation and a threshold of 100,000 cells/ml during the rest of lactation for cows with CM during the first 90 days in milk. Moreover, this criterion also most efficiently identified cows infected with major pathogens only at dry-off. The success of the criteria used for identifying infected and uninfected cows will, however, depend on herd characteristics, such as prevalence of infection and type of pathogens present in the herd.

Protein regulator of cytokinesis-1 expression: prognostic value in lung squamous cell carcinoma patients

PubMed Central

Zhan, Ping; Xi, Guang-Min; Liu, Hong-Bing; Liu, Ya-Fang; Xu, Wu-Jian; Zhu, Qingqing; Zhou, Ze-Jun; Miao, Ying-Ying; Wang, Xiao-Xia; Jin, Jia-Jia

2017-01-01

Background Protein regulator of cytokinesis-1 (PRC1) has been shown to participate in the completion of cytokinesis, and it is dysregulated in cancer processes. However, its relevance in lung squamous cell carcinoma (SCC) remained largely unknown. We aimed to study the expression pattern of PRC1 and assess its clinical significance in lung SCC. Methods PRC1 protein expression in human lung SCC and adjacent normal lung tissues was detected by immunohistochemistry. PRC1 expression was assessed in association with clinicopathological features and clinical outcomes of lung SCC patients. Results In lung SCC tissues, PRC1 protein expression was significantly higher than those in paired normal lung tissues. The lung SCC patients with PRC1 overexpression had an advanced pathological stage (TNM stage), positive lymph node metastasis, and a shorter overall survival (OS) time more frequently than patients with low PRC1 expression. Additional, PRC1 expression was also shown to be poor as a prognostic factor for OS in patients with lung SCC. Conclusions Our study indicated that aberrant expression of PRC1 may point to biochemical recurrence in lung SCC. This highlights its potential as a valuable prognostic marker for lung SCC. PMID:28840006

Wild-type p53 reactivation by small-molecule Minnelide™ in human papillomavirus (HPV)-positive head and neck squamous cell carcinoma.

PubMed

Caicedo-Granados, Emiro; Lin, Rui; Fujisawa, Caitlin; Yueh, Bevan; Sangwan, Veena; Saluja, Ashok

2014-12-01

The incidence of high-risk human papillomavirus (HR-HPV) head and neck squamous cell carcinoma (HNSCC) continues to increase, particularly oropharyngeal squamous cell carcinoma (OPSCC) cases. The inactivation of the p53 tumor suppressor gene promotes a chain of molecular events, including cell cycle progression and apoptosis resistance. Reactivation of wild-type p53 function is an intriguing therapeutic strategy. The aim of this study was to investigate whether a novel compound derived from diterpene triepoxide (Minnelide™) can reactivate wild-type p53 function in HPV-positive HNSCC. For all of our in vitro experiments, we used 2 HPV-positive HNSCC cell lines, University of Michigan squamous cell carcinoma (UM-SCC) 47 and 93-VU-147, and 2 HPV-positive human cervical cancer cell lines, SiHa and CaSki. Cells were treated with different concentrations of triptolide and analyzed for p53 activation. Mice bearing UM-SCC 47 subcutaneous xenografts and HPV-positive patient-derived tumor xenografts were treated with Minnelide and evaluated for tumor growth and p53 activation. In HPV-positive HNSCC, Minnelide reactivated p53 by suppressing E6 oncoprotein. Activation of apoptosis followed, both in vitro and in vivo. In 2 preclinical HNSCC animal models (a subcutaneous xenograft model and a patient-derived tumor xenograft model), Minnelide reactivated p53 function and significantly decreased tumor progression and tumor volume. Triptolide and Minnelide caused cell death in vitro and in vivo in HPV-positive HNSCC by reactivating wild-type p53 and thus inducing apoptosis. In addition, in 2 HPV-positive HNSCC animal models, Minnelide decreased tumor progression and induced apoptosis. Copyright © 2014 Elsevier Ltd. All rights reserved.

Integration of High-Risk Human Papillomavirus into Cellular Cancer-Related Genes in Head and Neck Cancer Cell Lines

PubMed Central

Walline, Heather M; Komarck, Christine M; McHugh, Jonathan B; Tang, Alice L; Owen, John H; Teh, Bin T; McKean, Erin; Glover, Thomas; Graham, Martin P; Prince, Mark E; Chepeha, Douglas B; Chinn, Steven B; Ferris, Robert L; Gollin, Susanne M; Hoffmann, Thomas K; Bier, Henning; Brakenhoff, Ruud; Bradford, Carol R; Carey, Thomas E

2017-01-01

Background HPV-positive oropharyngeal cancer is generally associated with excellent response to therapy, but some HPV-positive tumors progress despite aggressive therapy. This study evaluates viral oncogene expression and viral integration sites in HPV16 and HPV18-positive squamous carcinoma cell lines. Methods E6-E7 alternate transcripts were assessed by RT-PCR. Detection of integrated papillomavirus sequences (DIPS-PCR) and sequencing identified viral insertion sites and affected host genes. Cellular gene expression was assessed across viral integration sites. Results All HPV-positive cell lines expressed alternate HPVE6/E7 splicing indicative of active viral oncogenesis. HPV integration occurred within cancer-related genes TP63, DCC, JAK1, TERT, ATR, ETV6, PGR, PTPRN2, and TMEM237 in 8 HNSCC lines but UM-SCC-105 and UM-GCC-1 had only intergenic integration. Conclusions HPV integration into cancer-related genes occurred in 7/9 HPV-positive cell lines and of these six were from tumors that progressed. HPV integration into cancer-related genes may be a secondary carcinogenic driver in HPV-driven tumors. PMID:28236344

Interplay between Notch1 and Notch3 promotes EMT and tumor initiation in squamous cell carcinoma.

PubMed

Natsuizaka, Mitsuteru; Whelan, Kelly A; Kagawa, Shingo; Tanaka, Koji; Giroux, Veronique; Chandramouleeswaran, Prasanna M; Long, Apple; Sahu, Varun; Darling, Douglas S; Que, Jianwen; Yang, Yizeng; Katz, Jonathan P; Wileyto, E Paul; Basu, Devraj; Kita, Yoshiaki; Natsugoe, Shoji; Naganuma, Seiji; Klein-Szanto, Andres J; Diehl, J Alan; Bass, Adam J; Wong, Kwok-Kin; Rustgi, Anil K; Nakagawa, Hiroshi

2017-11-24

Notch1 transactivates Notch3 to drive terminal differentiation in stratified squamous epithelia. Notch1 and other Notch receptor paralogs cooperate to act as a tumor suppressor in squamous cell carcinomas (SCCs). However, Notch1 can be stochastically activated to promote carcinogenesis in murine models of SCC. Activated form of Notch1 promotes xenograft tumor growth when expressed ectopically. Here, we demonstrate that Notch1 activation and epithelial-mesenchymal transition (EMT) are coupled to promote SCC tumor initiation in concert with transforming growth factor (TGF)-β present in the tumor microenvironment. We find that TGFβ activates the transcription factor ZEB1 to repress Notch3, thereby limiting terminal differentiation. Concurrently, TGFβ drives Notch1-mediated EMT to generate tumor initiating cells characterized by high CD44 expression. Moreover, Notch1 is activated in a small subset of SCC cells at the invasive tumor front and predicts for poor prognosis of esophageal SCC, shedding light upon the tumor promoting oncogenic aspect of Notch1 in SCC.

Two different protein expression profiles of oral squamous cell carcinoma analyzed by immunoprecipitation high-performance liquid chromatography.

PubMed

Kim, Soung Min; Jeong, Dasul; Kim, Min Keun; Lee, Sang Shin; Lee, Suk Keun

2017-08-08

Oral squamous cell carcinoma (OSCC) is one of the most dangerous cancers in the body, producing serious complications with individual behaviors. Many different pathogenetic factors are involved in the carcinogenesis of OSCC. Cancer cells derived from oral keratinocytes can produce different carcinogenic signaling pathways through differences in protein expression, but their protein expression profiles cannot be easily explored with ordinary detection methods. The present study compared the protein expression profiles between two different types of OSCCs, which were analyzed through immunoprecipitation high-performance liquid chromatography (IP-HPLC). Two types of squamous cell carcinoma (SCC) occurred in a mandibular (SCC-1) and maxillary gingiva (SCC-2), but their clinical features and progression were quite different from each other. SCC-1 showed a large gingival ulceration with severe halitosis and extensive bony destruction, while SCC-2 showed a relatively small papillary gingival swelling but rapidly grew to form a large submucosal mass, followed by early cervical lymph node metastasis. In the histological observation, SCC-1 was relatively well differentiated with a severe inflammatory reaction, while SCC-2 showed severely infiltrative growth of each cancer islets accompanied with a mild inflammatory reaction. IP-HPLC analysis revealed contrary protein expression profiles analyzed by 72 different oncogenic proteins. SCC-1 showed more cellular apoptosis and invasive growth than SCC-2 through increased expression of caspases, MMPs, p53 signaling, FAS signaling, TGF-β1 signaling, and angiogenesis factors, while SCC-2 showed more cellular growth and survival than SCC-1 through the increased expression of proliferating factors, RAS signaling, eIF5A signaling, WNT signaling, and survivin. The increased trends of cellular apoptosis and invasiveness in the protein expression profiles of SCC-1 were implicative of its extensive gingival ulceration and bony destruction, while the increased trends of cellular proliferation and survival in the protein profile of SCC-2 were implicative of its rapid growing tumor mass and early lymph node metastasis. These analyses of the essential oncogenic protein expression profiles in OSCC provide important information for genetic counseling or customized gene therapy in cancer treatment. Therefore, protein expression profile analysis through IP-HPLC is helpful not only for the molecular genetic diagnosis of cancer but also in identifying target molecules for customized gene therapy in near future.

The Polycomb proteins RING1B and EZH2 repress the tumoral pro-inflammatory function in metastasizing primary cutaneous squamous cell carcinoma.

PubMed

Hernández-Ruiz, Eugenia; Toll, Agustí; García-Diez, Irene; Andrades, Evelyn; Ferrandiz-Pulido, Carla; Masferrer, Emili; Yébenes, Mireia; Jaka, Ane; Gimeno, Javier; Gimeno, Ramón; García-Patos, Vicenç; Pujol, Ramón M; Hernández-Muñoz, Inmaculada

2018-03-08

Cutaneous squamous cell carcinoma (cSCC) is the second most common malignancy in humans and approximately 5% metastasize, usually to regional lymph nodes. Epigenetic regulation of gene expression may allow tumoral cells to acquire new functions in order to escape from the primary tumor. The aim of this study was to investigate the expression and function of proteins of the Polycomb family of epigenetic regulators in the metastatic process of cSCC. A higher expression of RING1B and EZH2 was detected by immunohistochemistry in a series of primary cSCC tumors that metastasized (MSCCs) when compared with non-metastasizing cSCCs (non-MSCCs). Stable downregulation of RING1B and EZH2 in cSCC cells results in enhanced expression of inflammatory cytokines and activation of the NF-κB signaling pathway. Accordingly, non-MSCCs display higher levels of membranous pS176-inhibitor of NF-kB kinase, and their stroma is enriched in neutrophils and eosinophils when compared with MSCCs. In vitro, hematopoietic cells exhibit a substantial migratory response to supernatants from Polycomb-depleted cSCC cells. Altogether, these data indicate that RING1B and EZH2 repress the innate inflammatory cSCC function and impair tumor immunosurveillance and suggest that patients with high-risk cSCCs could benefit from clinical therapies addressed to harness the immune response.

The methoxychlor metabolite, HPTE, inhibits rat luteal cell progesterone production.

PubMed

Akgul, Yucel; Derk, Raymond C; Meighan, Terence; Rao, K Murali Krishna; Murono, Eisuke P

2011-07-01

The methoxychlor metabolite, HPTE, was shown to inhibit P450-cholesterol side-chain cleavage (P450scc) activity resulting in decreased progesterone production by cultured ovarian follicular cells in previous studies. It is not known whether HPTE has any effect on progesterone formation by the corpus luteum. Exposure to 100 nM HPTE reduced progesterone production by luteal cells with progressive declines to <22% of control at 500 nM HPTE. Similarly, HPTE progressively inhibited progesterone formation and P450scc catalytic activity of hCG- or 8 Br-cAMP-stimulated luteal cells. However, HPTE did not alter mRNA and protein levels of P450scc. Compounds acting as estrogen (17 β-estradiol, bisphenol-A or octylphenol), antiestrogen (ICI) or antiandrogen (monobutyl phthalate, flutamide or M-2) added alone to luteal cells did not mimic the action of HPTE on progesterone and P450scc activity. These results suggest that HPTE directly inhibits P450scc catalytic activity resulting in reduced progesterone formation, and this action was not mediated through estrogen or androgen receptors. Published by Elsevier Inc.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hinshaw, Stephen M.; Makrantoni, Vasso; Kerr, Alastair

The cohesin ring holds newly replicated sister chromatids together until their separation at anaphase. Initiation of sister chromatid cohesion depends on a separate complex, Scc2NIPBL/Scc4Mau2 (Scc2/4), which loads cohesin onto DNA and determines its localization across the genome. Proper cohesin loading is essential for cell division, and partial defects cause chromosome missegregation and aberrant transcriptional regulation, leading to severe developmental defects in multicellular organisms. We present here a crystal structure showing the interaction between Scc2 and Scc4. Scc4 is a TPR array that envelops an extended Scc2 peptide. Using budding yeast, we demonstrate that a conserved patch on the surfacemore » of Scc4 is required to recruit Scc2/4 to centromeres and to build pericentromeric cohesion. These findings reveal the role of Scc4 in determining the localization of cohesin loading and establish a molecular basis for Scc2/4 recruitment to centromeres.« less

In vivo study of ALA PLGA nanoparticles-mediated PDT for treating cutaneous squamous cell carcinoma

NASA Astrophysics Data System (ADS)

Wang, Xiaojie; Shi, Lei; Huang, Zheng; Wang, Xiuli

2014-09-01

Background: Squamous cell carcinoma (SCC) is a common skin cancer and its treatment is still a challenge. Although topical photodynamic therapy (PDT) is effective for treating in situ and superficial SCC, the effectiveness of topical ALA delivery to thick SCC can be limited by its bioavailability. Polylactic-co-glycolic acid nanopartieles (PLGA NPs) might provide a promising ALA delivery strategy. The aim of this study was to evaluate the efficacy of ALA PLGA NPs PDT for the treatment of cutaneous SCC in a mouse model. Methods: ALA loaded PLGA NPs were prepared and characterized. The therapeutic efficacy of ALA PLGA NP mediated PDT in treating UV-induced cutaneous SCC in the mice model were examined. Results: In vivo study showed that ALA PLGA NPs PDT were more effective than free ALA of the same concentration in treating mouse cutaneous SCC. Conclusion: ALA PLGA NPs provides a promising strategy for delivering ALA and treating cutaneous SCC.

Effects of milk somatic cell counts on some physicochemical and functional characteristics of skim and whole milk powders.

PubMed

Sert, Durmuş; Mercan, Emin; Aydemir, Serdar; Civelek, Mustafa

2016-07-01

The aim of this work was to study the influence of milk somatic cell count (SCC) levels on spray-dried milk powders. For this reason, 3 cow milks with different SCC (<300,000, 300,000-700,000, >700,000 SCC/mL) were processed into skim (SMP) and whole milk powder (WMP). The effect of SCC on the physicochemical and functional characteristics of the milk powders and textural properties of set-type yogurts produced from reconstituted milk powders with different SCC was evaluated. A crucial difference was noted between milk powders depending on different SCC. Protein values and ash content of powder samples decreased correlatively with increasing SCC. The hydroxymethylfurfural content of SMP was higher than WMP. We noted an increase in hydroxymethylfurfural content of both SMP and WMP depending on elevated SCC. Solubility index of SMP and WMP was 1.280 to 1.632 and 0.940 to 1.208mL, respectively; with increasing SCC, solubility index was affected adversely. The highest foam stability was determined in SMP containing >700,000 SCC. Bulk density of SMP and WMP was between 0.682 and 0.708 and 0.660 to 0.685g/cm(3), respectively. An increase was observed in scorched particle of both SMP and WMP depending on increasing SCC. We found significant differences in particle size distribution of milk powders produced from milk with SCC at different levels. Although WMP had more uniform and big particle structure, SMP had more specific area. A negative correlation was noted between yogurt texture and SCC. Results indicate that milk SCC has negative influences on milk powder quality. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Targeting of Survivin Pathways by YM155 Inhibits Cell Death and Invasion in Oral Squamous Cell Carcinoma Cells.

PubMed

Zhang, Wei; Liu, Yuan; Li, Yu Feng; Yue, Yun; Yang, Xinghua; Peng, Lin

2016-01-01

Specific overexpression in cancer cells and evidence of oncogenic functions make Survivin an attractive target in cancer therapy. The small molecule compound YM155 has been described as the first "Survivin suppressant" but molecular mechanisms involved in its biological activity and its clinical potential remain obscure. Survivin protein plays critical roles in oral squamous cell carcinoma (OSCC), suggesting that YM155 would be extremely valuable for OSCC. In this study, we tested our hypothesis whether YM155 could be an effective inhibitor of cell growth, invasion and angiogenesis in oral squamous cell carcinoma (OSCC) cells. SCC9 and SCC25 were treated with different concentration of YM155 for indicated time. Using MTT assay and flow cytometry analysis to detect cell growth and apoptosis; Using transwell and Wound healing assay to detect migration and invasion; Using reverse transcription-PCR, Western blotting and electrophoretic mobility shift assay for measuring gene and protein expression, and DNA binding activity of NF-x03BA;B. YM155 inhibited survivin-rich expressed SCC9 cell growth in a dose- and time dependent manner. This was accompanied by increased apoptosis and concomitant attenuation of NF-x03BA;B and downregulation of NF-x03BA;B downstream genes MMP-9, resulting in the inhibition of SCC9 cell migration and invasion in vitro and caused antitumor activity and anti metastasis in vivo. YM155 treatment did not affect cell growth, apoptosis and invasion of surviving-poor expressed SCC25 cells in vitro. YM155 is a potent inhibitor of progression of SCC9 cells, which could be due to attenuation of survivin signaling processes. Our findings provide evidence showing that YM155 could act as a small molecule survivin inhibitor on survivin-rich expressed SCC9 cells in culture as well as when grown as tumor in a xenograft model. We also suggest that survivin could be further developed as a potential therapeutic agent for the treatment of survivin-rich expressed OSCC. © 2016 The Author(s) Published by S. Karger AG, Basel.

Nonlinear spectral imaging of human normal skin, basal cell carcinoma and squamous cell carcinoma based on two-photon excited fluorescence and second-harmonic generation

NASA Astrophysics Data System (ADS)

Xiong, S. Y.; Yang, J. G.; Zhuang, J.

2011-10-01

In this work, we use nonlinear spectral imaging based on two-photon excited fluorescence (TPEF) and second harmonic generation (SHG) for analyzing the morphology of collagen and elastin and their biochemical variations in basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and normal skin tissue. It was found in this work that there existed apparent differences among BCC, SCC and normal skin in terms of their thickness of the keratin and epithelial layers, their size of elastic fibers, as well as their distribution and spectral characteristics of collagen. These differences can potentially be used to distinguish BCC and SCC from normal skin, and to discriminate between BCC and SCC, as well as to evaluate treatment responses.

Eldecalcitol (ED-71), an analog of 1α,25(OH)2D3, inhibits the growth of squamous cell carcinoma (SCC) cells in vitro and in vivo by down-regulating expression of heparin-binding protein 17/fibroblast growth factor-binding protein-1 (HBp17/FGFBP-1) and FGF-2.

PubMed

Shintani, T; Takatsu, F; Rosli, S N Z; Usui, E; Hamada, A; Sumi, K; Hayashido, Y; Toratani, S; Okamoto, Tetsuji

2017-10-01

Heparin-binding protein 17 (HBp17)/fibroblast growth factor-binding protein-1 (FGFBP-1) was first purified from medium conditioned by A431 cells for its capacity to bind to fibroblast growth factors 1 and 2 (FGF-1 and -2). Among FGF family members, FGF-2 is a potent mitogen for various cell types, including vascular endothelial cells, fibroblasts, and cancer cells such as oral squamous cell carcinoma (OSCC) cells. Besides being well known in bone metabolism, the active form of vitamin D 3 , i.e., 1α,25(OH) 2 D 3 (1,25D 3 ), was reported to have protective effects for heart disease and cancer. Previously, we reported that 1,25D 3 inhibited HBp17/FGFBP-1 expression in OSCC cell lines through NF-κB inhibition (IκBα activation) and resulted in the inactivation of FGF-2. In this study, we examined the potential anti-tumor effect of ED-71, an analog of 1α,25(OH) 2 D 3 , for squamous cell carcinoma cells in vitro and in vivo. The cell lines used were OSCC cell lines (NA-HO-1-n-1 and UE-HO-1-u-1), established from oral cancer patients in our laboratory, and an epidermoid carcinoma/SCC cell line (A431). The growth assay in serum-free culture revealed that ED-71 inhibited the growth of the cancer cell lines in a dose-dependent manner. In addition, ED-71 suppressed HBp17/FGFBP-1 expression by inhibiting the NF-κB pathway as did 1,25D 3 . Furthermore, a luciferase reporter assay revealed that the promoter activity of HBp17/FGFBP-1 (region between -217 and +61) was down-regulated by ED-71. Oral administration of ED-71 significantly inhibited the growth of A431-derived tumors in athymic nude mice. Immunohistochemical analysis revealed that the expression of HBp17/FGFBP-1, FGF-2, CD31, and Ki-67 in the tumors of ED71-treated group was down-regulated in comparison to control. These results suggest that ED-71 possesses potential anti-tumor activity for SCCs both in vitro and in vivo. This compound may act directly on the tumor cells or on endothelial cells by modulating the tumor microenvironment.

Sarcomatoid carcinoma associated with small cell carcinoma of the urinary bladder: a series of 28 cases.

PubMed

Urrea, Yuly Ramirez; Epstein, Jonathan I

2017-09-01

The association of sarcomatoid carcinoma (SC) with small cell carcinoma (SCC) has not been systematically studied. We identified 39 consult cases between 2001 and 2016 with available slides for review in 28 cases. There were 19 men and 9 women (mean age: 78 years [51-89]). In 26 (92.8%) cases, the sarcomatoid component had nonspecific malignant spindle cells, 4 (14%) chondrosarcoma, 2 (7%) myxoid sarcomatous, 1 (3.5%) osteosarcoma, and 1 (3.5%) rhabdomyosarcoma. The predominant component was SCC in 11 (39%) cases, urothelial carcinoma in 6 (21%), sarcomatoid in 3 (10%), and equal sarcomatoid and SCC in 8 (29%). There were 3 morphological groups: group 1 (18/28 [64%]) showed a gradual transition from SCC to other components; group 2 (5/28 [18%]) had an abrupt transition from SCC to other components; and in group 3 (5/28 [18%]), the SCC was separate from other components. In group 1, 12 (66%) cases of SCC showed a gradual transition to sarcomatoid areas; 3 (17%) to urothelial carcinoma; and 3 (17%) to multiple components including squamous cell carcinoma, urothelial carcinoma, and sarcomatoid. Mortality did not differ based on pathological groups. The 36-month actuarial risk of death was 64.3%. The multitude of different components in these tumors is further evidence of the remarkable ability of carcinoma of the bladder to show divergent differentiation with, in some cases, gradual transition between SCC and other elements including sarcomatoid. Greater recognition of this entity with chemotherapy targeted to the various histological elements may have important therapeutic implications. Copyright © 2017 Elsevier Inc. All rights reserved.

Spotlighting the role of photodynamic therapy in cutaneous malignancy: an update and expansion.

PubMed

Ross, Kate; Cherpelis, Basil; Lien, Mary; Fenske, Neil

2013-12-01

Topical photodynamic therapy (PDT) is an option for the treatment of cutaneous malignancy. To present an update and expansion on a previous review of the use of PDT in the current literature in the treatment of actinic keratoses (AK), superficial and nodular basal cell carcinoma (sBCC, nBCC), squamous cell carcinoma (SCC), Bowen's disease, cutaneous T cell lymphoma (CTCL), malignant melanoma, and its use in chemoprevention. Extensive PubMed search January 2013. We find sufficient evidence to recommend the use of PDT in certain patients in the treatment of AK, Bowen's disease, sBCC, and nBCC. It is especially useful in those with contraindications to surgery, widespread areas of involvement, and large lesions. Not only can it be considered superior to other therapies as far as recovery time, tolerance, and cosmetic outcomes, but it also should be considered, when indicated, as first-line treatment in the above conditions. Investigations continue for the use of PDT in the treatment of melanoma, SCC, chemoprevention, and CTCL. © 2013 by the American Society for Dermatologic Surgery, Inc. Published by Wiley Periodicals, Inc.

STRESS CORROSION CRACK GROWTH RESPONSE FOR ALLOY 152/52 DISSIMILAR METAL WELDS IN PWR PRIMARY WATER

DOE Office of Scientific and Technical Information (OSTI.GOV)

Toloczko, Mychailo B.; Olszta, Matthew J.; Overman, Nicole R.

2015-08-15

As part of ongoing research into primary water stress corrosion cracking (PWSCC) susceptibility of alloy 690 and its welds, SCC tests have been conducted on alloy 152/52 dissimilar metal (DM) welds with cracks positioned with the goal to assess weld dilution and fusion line effects on SCC susceptibility. No increased crack growth rate was found when evaluating a 20% Cr dilution zone in alloy 152M joined to carbon steel (CS) that had not undergone a post-weld heat treatment (PWHT). However, high SCC crack growth rates were observed when the crack reached the fusion line of that material where it propagatedmore » both on the fusion line and in the heat affected zone (HAZ) of the carbon steel. Crack surface and crack profile examinations of the specimen revealed that cracking in the weld region was transgranular (TG) with weld grain boundaries not aligned with the geometric crack growth plane of the specimen. The application of a typical pressure vessel PWHT on a second set of alloy 152/52 – carbon steel DM weld specimens was found to eliminate the high SCC susceptibility in the fusion line and carbon steel HAZ regions. PWSCC tests were also performed on alloy 152-304SS DM weld specimens. Constant K crack growth rates did not exceed 5x10-9 mm/s in this material with post-test examinations revealing cracking primarily on the fusion line and slightly into the 304SS HAZ.« less

Correlation Between Squamous Cell Carcinoma Antigen Level and the Clinicopathological Features of Early-Stage Cervical Squamous Cell Carcinoma and the Predictive Value of Squamous Cell Carcinoma Antigen Combined With Computed Tomography Scan for Lymph Node Metastasis.

PubMed

Xu, Dianbo; Wang, Danbo; Wang, Shuo; Tian, Ye; Long, Zaiqiu; Ren, Xuemei

2017-11-01

The aim of this study was to analyze the relationship between serum squamous cell carcinoma antigen (SCC-Ag) and the clinicopathological features of cervical squamous cell carcinoma. The value of SCC-Ag and computed tomography (CT) for predicting lymph node metastasis (LNM) was evaluated. A total of 197 patients with International Federation of Gynecology and Obstetrics stages IB to IIA cervical squamous cell carcinoma who underwent radical surgery were enrolled in this study. The SCC-Ag was measured, and CT scans were used for the preoperative assessment of lymph node status. Increased preoperative SCC-Ag levels were associated with International Federation of Gynecology and Obstetrics stage (P = 0.001), tumor diameter of greater than 4 cm (P < 0.001), lymphovascular invasion (P = 0.001), LNM (P < 0.001), and greater than one half stromal infiltration (P < 0.001). Multivariate analysis identified LNM (P < 0.001, odds ratio [OR] = 4.399), tumor diameter of greater than >4 cm (P = 0.001, OR = 4.019), and greater than one half stromal infiltration (P = 0.002, OR = 3.680) as independent factors affecting SCC-Ag greater than or equal to 2.35 ng/mL. In the analysis of LNM, SCC-Ag greater than or equal to 2.35 ng/mL (P < 0.001, OR = 4.825) was an independent factor for LNM. The area under the receiver operator characteristic curve (AUC) of SCC-Ag was 0.763 for all patients, and 0.805 and 0.530 for IB1 + IIA1 and IB2 + IIA2 patients, respectively; 2.35 ng/mL was the optimum cutoff for predicting LNM. The combination of CT and SCC-Ag showed a sensitivity and specificity of 82.9% and 66% in parallel tests, and 29.8% and 93.3% in serial tests, respectively. The increase of SCC-Ag level in the preoperative phase means that there may be a pathological risk factor for postoperative outcomes. The SCC-Ag (≥2.35 ng/mL) may be a useful marker for predicting LNM of cervical cancer, especially in stages IB1 and IIA1, and the combination of SCC-Ag and CT may help identify patients with LNM to provide them with the most appropriate therapeutic approach.

Tumor-produced, active Interleukin-1 {beta} regulates gene expression in carcinoma-associated fibroblasts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dudas, Jozsef, E-mail: Jozsef.Dudas@i-med.ac.at; Fullar, Alexandra, E-mail: fullarsz@gmail.com; 1st Institute of Pathology and Experimental Cancer Research, Semmelweis University, Ulloei ut 26, H-1085 Budapest

2011-09-10

Recently we described a co-culture model of periodontal ligament (PDL) fibroblasts and SCC-25 lingual squamous carcinoma cells, which resulted in conversion of normal fibroblasts into carcinoma-associated fibroblasts (CAFs), and in epithelial-mesenchymal transition (EMT) of SCC-25 cells. We have found a constitutive high interleukin-1{beta} (IL1-{beta}) expression in SCC-25 cells in normal and in co-cultured conditions. In our hypothesis a constitutive IL1-{beta} expression in SCC-25 regulates gene expression in fibroblasts during co-culture. Co-cultures were performed between PDL fibroblasts and SCC-25 cells with and without dexamethasone (DEX) treatment; IL1-{beta} processing was investigated in SCC-25 cells, tumor cells and PDL fibroblasts were treated withmore » IL1-{beta}. IL1-{beta} signaling was investigated by western blot and immunocytochemistry. IL1-{beta}-regulated genes were analyzed by real-time qPCR. SCC-25 cells produced 16 kD active IL1-{beta}, its receptor was upregulated in PDL fibroblasts during co-culture, which induced phosphorylation of interleukin-1 receptor-associated kinase-1 (IRAK-1), and nuclear translocalization of NF{kappa}B{alpha}. Several genes, including interferon regulatory factor 1 (IRF1) interleukin-6 (IL-6) and prostaglandin-endoperoxide synthase 2 (COX-2) were induced in CAFs during co-culture. The most enhanced induction was found for IL-6 and COX-2. Treatment of PDL fibroblasts with IL1-{beta} reproduced a time- and dose-dependent upregulation of IL1-receptor, IL-6 and COX-2. A further proof was achieved by DEX inhibition for IL1-{beta}-stimulated IL-6 and COX-2 gene expression. Constitutive expression of IL1-{beta} in the tumor cells leads to IL1-{beta}-stimulated gene expression changes in tumor-associated fibroblasts, which are involved in tumor progression. -- Graphical abstract: SCC-25 cells produce active, processed IL1-{beta}. PDL fibroblasts possess receptor for IL1-{beta}, and its expression is increased 4.56-times in the presence of SCC-25 tumor cells. IL1-{beta} receptor expression in fibroblasts, especially in CAFs represents a major option in coordination of fibroblast and tumor behavior. A key event in IL1-{beta} signaling, the phosphorylation of IRAK1, occurred in co-cultured fibroblasts, which has lead to nuclear translocation of NF{kappa}B{alpha}, and finally to induction of several genes, including BDNF, IRF1, IL-6 and COX-2. The most enhanced induction was found for IL-6 and COX-2.« less

Physical Association of Saccharomyces cerevisiae Polo-like Kinase Cdc5 with Chromosomal Cohesin Facilitates DNA Damage Response.

PubMed

Pakchuen, Sujiraporn; Ishibashi, Mai; Takakusagi, Emi; Shirahige, Katsuhiko; Sutani, Takashi

2016-08-12

At the onset of anaphase, a protease called separase breaks the link between sister chromatids by cleaving the cohesin subunit Scc1. This irreversible step in the cell cycle is promoted by degradation of the separase inhibitor, securin, and polo-like kinase (Plk) 1-dependent phosphorylation of the Scc1 subunit. Plk could recognize substrates through interaction between its phosphopeptide interaction domain, the polo-box domain, and a phosphorylated priming site in the substrate, which has been generated by a priming kinase beforehand. However, the physiological relevance of this targeting mechanism remains to be addressed for many of the Plk1 substrates. Here, we show that budding yeast Plk1, Cdc5, is pre-deposited onto cohesin engaged in cohesion on chromosome arms in G2/M phase cells. The Cdc5-cohesin association is mediated by direct interaction between the polo-box domain of Cdc5 and Scc1 phosphorylated at multiple sites in its middle region. Alanine substitutions of the possible priming phosphorylation sites (scc1-15A) impair Cdc5 association with chromosomal cohesin, but they make only a moderate impact on mitotic cell growth even in securin-deleted cells (pds1Δ), where Scc1 phosphorylation by Cdc5 is indispensable. The same scc1-15A pds1Δ double mutant, however, exhibits marked sensitivity to the DNA-damaging agent phleomycin, suggesting that the priming phosphorylation of Scc1 poses an additional layer of regulation that enables yeast cells to adapt to genotoxic environments. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

The interplay between hepatic stellate cells and hepatocytes in an in vitro model of NASH.

PubMed

Barbero-Becerra, Varenka J; Giraudi, Pablo J; Chávez-Tapia, Norberto C; Uribe, Misael; Tiribelli, Claudio; Rosso, Natalia

2015-10-01

A complex interplay exists between hepatocytes and hepatic stellate cells (HSC) in hepatic fibrogenesis. The activation of HSCs after liver injury leads to production of extracellular matrix (ECM). Co-culture models could be useful to mimic the liver microenvironment. This study evaluates the effect of free fatty acids (FFA) on HSC cells and the interplay with hepatocytes via both soluble-mediator and cell-cell contact. The human hepatocyte cell line (HuH7) and HSC cells (LX2) were exposed to FFA for 24 h in 3 different experimental set-ups: (A) monoculture of HSC; (B) Transwell® system (effect of soluble mediators); and (C) Simultaneous Co-Culture (SCC) (cell-to-cell connections). Intracellular FFA accumulation was assessed qualitatively (microscopy) and quantitatively (flow cytometry); the activation of HSC (alpha smooth muscle actin, α-SMA) expression of ECM components were quantified by RT-PCR. FFA exposure induces intracellular fat accumulation in all the experimental set-up but the expression of α-SMA was significantly increased only in SCC. On the contrary, the expression of ECM was substantially decreased in the transwell® system. The HSC activation is independent of FFA accumulation but requires cell-to-cell interaction with hepatocyte. On the contrary, the gene regulation of ECM components seems to occur through paracrine mediators. Copyright © 2015 Elsevier Ltd. All rights reserved.

Aberrant expression of the tight junction molecules claudin-1 and zonula occludens-1 mediates cell growth and invasion in oral squamous cell carcinoma.

PubMed

Babkair, Hamzah; Yamazaki, Manabu; Uddin, Md Shihab; Maruyama, Satoshi; Abé, Tatsuya; Essa, Ahmed; Sumita, Yoshimasa; Ahsan, Md Shahidul; Swelam, Wael; Cheng, Jun; Saku, Takashi

2016-11-01

We reported that altered cell contact mediated by E-cadherin is an initial event in the pathogenesis of oral epithelial malignancies. To assess other effects of cell adhesion, we examined the expression levels of tight junction (TJ) molecules in oral carcinoma in situ (CIS) and squamous cell carcinoma (SCC). To identify changes in the expression of TJ molecules, we conducted an analysis of the immunohistochemical profiles of claudin-1 (CLDN-1) and zonula occludens-1 (ZO-1) in surgical specimens acquired from patients with oral SCC containing foci of epithelial dysplasia or from patients with CIS. We used immunofluorescence, Western blotting, reverse-transcription polymerase chain reaction, and RNA interference to evaluate the functions of CLDN-1 and ZO-1 in cultured oral SCC cells. TJ molecules were not detected in normal oral epithelial tissues but were expressed in SCC/CIS cells. ZO-1 was localized within the nucleus of proliferating cells. When CLDN-1 expression was inhibited by transfecting cells with specific small interference RNAs, SCC cells dissociated, and their ability to proliferate and invade Matrigel was inhibited. In contrast, although RNA interference-mediated inhibition of ZO-1 expression did not affect cell morphology, it inhibited cell proliferation and invasiveness. Our findings indicated that the detection of TJ molecules in the oral epithelia may serve as a marker for the malignant phenotype of cells in which CLDN-1 regulates proliferation and invasion. Copyright © 2016 Elsevier Inc. All rights reserved.

Novel Pactamycin Analogs Induce p53 Dependent Cell-Cycle Arrest at S-Phase in Human Head and Neck Squamous Cell Carcinoma (HNSCC) Cells

PubMed Central

Guha, Gunjan; Liang, Xiaobo; Kulesz-Martin, Molly F.; Mahmud, Taifo; Indra, Arup Kumar; Ganguli-Indra, Gitali

2015-01-01

Pactamycin, although putatively touted as a potent antitumor agent, has never been used as an anticancer drug due to its high cytotoxicity. In this study, we characterized the effects of two novel biosynthetically engineered analogs of pactamycin, de-6MSA-7-demethyl-7-deoxypactamycin (TM-025) and 7-demethyl-7-deoxypactamycin (TM-026), in head and neck squamous cell carcinoma (HNSCC) cell lines SCC25 and SCC104. Both TM-025 and TM-026 exert growth inhibitory effects on HNSCC cells by inhibiting cell proliferation. Interestingly, unlike their parent compound pactamycin, the analogs do not inhibit synthesis of nascent protein in a cell-based assay. Furthermore, they do not induce apoptosis or autophagy in a dose- or a time-dependent manner, but induce mild senescence in the tested cell lines. Cell cycle analysis demonstrated that both analogs significantly induce cell cycle arrest of the HNSCC cells at S-phase resulting in reduced accumulation of G2/M-phase cells. The pactamycin analogs induce expression of cell cycle regulatory proteins including master regulator p53, its downstream target p21Cip1/WAF1, p27kip21, p19, cyclin E, total and phospho Cdc2 (Tyr15) and Cdc25C. Besides, the analogs mildly reduce cyclin D1 expression without affecting expression of cyclin B, Cdk2 and Cdk4. Specific inhibition of p53 by pifithrin-α reduces the percentage of cells accumulated in S-phase, suggesting contribution of p53 to S-phase increase. Altogether, our results demonstrate that Pactamycin analogs TM-025 and TM-026 induce senescence and inhibit proliferation of HNSCC cells via accumulation in S-phase through possible contribution of p53. The two PCT analogs can be widely used as research tools for cell cycle inhibition studies in proliferating cancer cells with specific mechanisms of action. PMID:25938491

Hypothyroidism Potentially Linked to Cutaneous Squamous Cell Carcinoma: Retrospective Study at a Single Tertiary Academic Medical Center.

PubMed

Ahadiat, Omeed; Higgins, Shauna; Trodello, Cameron; Talmor, Guy; Kokot, Niels; Wysong, Ashley

2018-01-01

There are multiple known risk factors for the development of cutaneous squamous cell carcinoma (SCC). To determine whether patients with cutaneous SCC have a higher prevalence of hypothyroidism than the general US population. A retrospective review was performed for patients seen at the University of Southern California with cutaneous SCC. Chart review was performed for the presence of hypothyroidism and thyroid replacement therapy before the diagnosis of SCC for each patient. Multiple prevalence studies were gathered from the literature for comparison, reporting the prevalence of overt and subclinical hypothyroidism in the general US population and/or elderly US population. Of the 265 patients diagnosed with SCC of the skin, 61 (23%) of patients were found to have a preceding diagnosis of hypothyroidism. The prevalence of hypothyroidism among the population of SCC patients was significantly greater than the prevalence of hypothyroidism (overt and subclinical) in any general and/or elderly US population reported. Patients with SCC of skin are more likely to have a history of hypothyroidism than the general population. The authors conclude that hypothyroidism may be linked to the development of cutaneous SCC.

The importance of staphylococci and threshold value of somatic cell count for diagnosis of sub-clinical mastitis in Pirlak sheep at mid-lactation.

PubMed

Ozenc, E; Seker, E; Baki Acar, D; Birdane, M K; Darbaz, I; Dogan, N

2011-12-01

This study investigated the bacterial agents causing sub-clinical mastitis and the mean somatic cell counts (SCC) of milk in Pirlak sheep at mid-lactation. The percentage of infected udder halves was 11.4% (53/464). The most frequently isolated species were coagulase-negative staphylococci (CNS) (64.2%), followed by Staphylococcus aureus (24.5%) and Escherichia coli (11.3%). Among the CNS, the most common species was Staphylococcus epidermidis (38.2%). The other species isolated from milk samples were Staphylococcus xylosus (17.7%), Staphylococcus chromogenes (14.7%), Staphylococcus simulans (8.8%) and Staphylococcus hyicus (8.8%). The mean SCC for culture positive and negative samples was 1742×10(3) and 161×10(3) cells/ml, respectively. A significant difference (p<0.05) was determined between with and without microbial growth groups in terms of the SCC values. Threshold limit for SCC was 374×10(3) cells/ml for Pirlak sheep. In conclusion, it was considered that SCC is an important predictor of sub-clinical mastitis in Pirlak sheep. This is the first study to describe the bacterial agents causing sub-clinical mastitis and threshold limit for SCC in Pirlak sheep in Turkey. © 2011 Blackwell Verlag GmbH.

Expression of matrix metalloproteinase-1, -2 and -3 in squamous cell carcinoma and actinic keratosis

PubMed Central

Tsukifuji, R; Tagawa, K; Hatamochi, A; Shinkai, H

1999-01-01

Matrix metalloproteinase (MMP) plays an important role in extracellular matrix degradation associated with cancer invasion. An expression of MMP-1 (interstitial collagenase), MMP-2 (72-kDa type IV collagenase) and MMP-3 (stromelysin-1) was investigated in squamous cell carcinoma (SCC) and its precancerous condition, actinic keratosis (AK), using in situ hybridization techniques. MMP-1 mRNA was detected in tumour cells and/or in stromal cells in all cases of SCC, four of six AKs adjacent to SCC and four of 16 AKs. MMP-2 and MMP-3 mRNAs were detected in SCC but not in AK. The expression of MMP-3 correlated to that of MMP-1 (P = 0.03) localized at the tumour mass and stroma of the invasive area, while MMP-2 mRNA was detected widely throughout the stroma independent of MMP-1 expression. Our results indicated that the expression of MMP-1, -2 and -3 showed different localization patterns, suggesting a unique role of each MMP in tumour progression. Moreover, MMP-1 expression could be an early event in the development of SCC, and AK demonstrating MMP-1 mRNA, might be in a more advanced dysplastic state, progressing to SCC. © 1999 Cancer Research Campaign PMID:10362121

MUC4 Regulates Cellular Senescence in Head and Neck Squamous Cell Carcinoma (HNSCC) through p16/Rb Pathway

PubMed Central

Macha, Muzafar A.; Rachagani, Satyanarayana; Pai, Priya; Gupta, Suprit; Lydiatt, Williams M.; Smith, Russell B.; Johansson, Sonny L.; Lele, Subodh M.; Kakar, Sham S.; Lee, John H.; Meza, Jane; Ganti, Apar K.; Jain, Maneesh; Batra, Surinder K.

2014-01-01

The limited effectiveness of therapy for patients with advanced stage Head and Neck Squamous Cell Carcinoma (HNSCC) or recurrent disease is a reflection of an incomplete understanding of the molecular basis of HNSCC pathogenesis. MUC4, a high molecular weight glycoprotein, is differentially overexpressed in many human cancers and implicated in cancer progression and resistance to several chemotherapies. However its clinical relevance and the molecular mechanisms through which it mediates HNSCC progression are not well understood. The present study revealed a significant up-regulation of MUC4 in 78% (68/87) of HNSCC tissues compared to 10% (1/10) in benign samples [p= 0.006, OR (95% C.I) = 10.74 (2.0 - 57.56)]. MUC4 knockdown (KD) in SCC1 and SCC10B HNSCC cell lines resulted in significant inhibition of growth in vitro and in vivo, increased senescence as indicated by an increase in the number of flat, enlarged and senescence-associated β-galactosidase (SA-β-Gal) positive cells. Decreased cellular proliferation was associated with G0/G1 cell cycle arrest and decrease expression of cell cycle regulatory proteins like cyclin E, cyclin D1 and decrease in BrdU incorporation. Mechanistic studies revealed upregulation of p16, pRb dephosphorylation and its interaction with HDAC1/2. This resulted in decreased histone acetylation (H3K9) at Cyclin E promoter leading to its downregulation. Orthotropic implantation of MUC4 KD SCC1 cells into the floor of the mouth of nude mice resulted in the formation of significantly small tumors (170±18.30 mg) compared to bigger tumors (375 ±17.29 mg) formed by control cells (p= 0.00007). In conclusion, our findings showed that MUC4 overexpression plays a critical role by regulating proliferation and cellular senescence of HNSCC cells. Downregulation of MUC4 may be a promising therapeutic approach for treating HNSCC patients. PMID:24747969

MUC4 regulates cellular senescence in head and neck squamous cell carcinoma through p16/Rb pathway.

PubMed

Macha, M A; Rachagani, S; Pai, P; Gupta, S; Lydiatt, W M; Smith, R B; Johansson, S L; Lele, S M; Kakar, S S; Farghaly, H; Lee, J H; Meza, J; Ganti, A K; Jain, M; Batra, S K

2015-03-26

The limited effectiveness of therapy for patients with advanced stage head and neck squamous cell carcinoma (HNSCC) or recurrent disease is a reflection of an incomplete understanding of the molecular basis of HNSCC pathogenesis. MUC4, a high molecular weight glycoprotein, is differentially overexpressed in many human cancers and implicated in cancer progression and resistance to several chemotherapies. However, its clinical relevance and the molecular mechanisms through which it mediates HNSCC progression are not well understood. This study revealed a significant upregulation of MUC4 in 78% (68/87) of HNSCC tissues compared with 10% positivity (1/10) in benign samples (P=0.006, odds ratio (95% confidence interval)=10.74 (2.0-57.56). MUC4 knockdown (KD) in SCC1 and SCC10B HNSCC cell lines resulted in significant inhibition of growth in vitro and in vivo, increased senescence as indicated by an increase in the number of flat, enlarged and senescence-associated β-galactosidase (SA-β-Gal)-positive cells. Decreased cellular proliferation was associated with G0/G1 cell cycle arrest and decrease expression of cell cycle regulatory proteins like cyclin E, cyclin D1 and decrease in BrdU incorporation. Mechanistic studies revealed upregulation of p16, pRb dephosphorylation and its interaction with histone deacetylase 1/2. This resulted in decreased histone acetylation (H3K9) at cyclin E promoter leading to its downregulation. Orthotopic implantation of MUC4 KD SCC1 cells into the floor of the mouth in nude mice resulted in the formation of significantly smaller tumors (170±18.30 mg) compared to those (375±17.29 mg) formed by control cells (P=0.00007). In conclusion, our findings showed that MUC4 overexpression has a critical role by regulating proliferation and cellular senescence of HNSCC cells. Downregulation of MUC4 may be a promising therapeutic approach for treating HNSCC patients.

Developing an Activity and Absorption-based Quality Control Platform for Chinese Traditional Medicine: Application to Zeng-Sheng-Ping

PubMed Central

Yin, Taijun; Yang, Guanyi; Ma, Yong; Xu, Beibei; Hu, Ming; You, Ming; Gao, Song

2015-01-01

Ethnopharmacological relevance Zeng-Sheng-Ping (ZSP) is a marketed Chinese traditional medicine used for cancer prevention. Aim of the study Currently, for the quality control of Chinese traditional medicines, marker compounds are not selected based on bioactivities and pharmaceutical behaviors in most of the cases. Therefore, even if the “quality” of the medicine is controlled, the pharmacological effect could still be inconsistent. The aim of this study is to establish an activity and absorption-based platform to select marker compound(s) for the quality control of Chinese traditional medicines. Materials and methods We used ZSP as a reference Chinese traditional medicine to establish the platform. Activity guided fractionation approach was used to purify the major components from ZSP. NMR and MS spectra were used to elucidate the structure of the isolated compounds. MTT assay against oral carcinoma cell line (SCC2095) was performed to evaluate the activities. UPLC-MS/MS was used to quantify the pure compounds in ZSP and the active fraction. The permeabilities of the identified compounds were evaluated in the Caco-2 cell culture model. The intracellular accumulation of the isolated compounds was evaluated in the SCC2095 cells. Results The major compounds were identified from ZSP. The contents, anti-proliferation activities, permeabilities, and intracellular accumulations of these compounds were also evaluated. The structure of these purified compounds were identified by comparing the NMR and MS data with those of references as rutaevine (1), limonin (2) , evodol (3), obacunone (4), fraxinellone (5), dictamnine (6), maackiain (7), trifolirhizin (8), and matrine (9). The IC50 of compounds 5, 6, and 7 against SCC2095 cells were significantly lower than that of ZSP. The uptake permeability of compounds 5, 6, and 7 were 2.58 ± 0. 3 × 10−5, 4.33 ± 0.5 × 10−5, and 4.27 ± 0.8 × 10−5 respectively in the Caco-2 cell culture model. The intracellular concentrations of these compounds showed that compounds 5, 6, and 7 were significantly accumulated inside the cells. Conclusion Based on the activity against oral carcinoma cell line as well as the absorption permeability, compound 5, 6, and 7 are selected as quality control markers for ZSP. A activity and absorption-based platform was established and successfully used for the quality control of ZSP. PMID:26099633

History of Allergy and Atopic Dermatitis in Relation to Squamous Cell and Basal Cell Carcinoma of the Skin

PubMed Central

Cheng, Judy; Zens, M. Scot; Duell, Eric; Perry, Ann E.; Chapman, M. Shane; Karagas, Margaret R.

2015-01-01

Background Little is known about whether history of allergies and atopy are related to the occurrence of keratinocyte cancers. Thus, we evaluated the association between history of allergies and atopy and the incidence of squamous cell carcinoma (SCC) and early onset basal cell carcinoma (BCC). Methods As part of a population-based case-control study, interviews were conducted with 1,050 residents of New Hampshire (375 early onset BCC cases and 251 controls, 254 SCC cases and 432 controls). Odds ratios (ORs) of SCC and early onset BCC and history of allergy and atopic dermatitis were computed using logistic regression, while controlling for potential confounding factors. Results An overall inverse association was observed between a history of allergy and early onset BCC (OR 0.61, 95% CI 0.38-0.97) but not SCC (OR 1.18, 95% CI 0.78-1.79). Among women, we found reduced ORs of both early onset BCC and for SCC in relation to allergy history (early onset BCC OR 0.53, 95% CI 0.31-0.92 and SCC OR 0.59, 95% CI 0.29-1.19). Among men, we observed no clear association with early onset BCC (OR 0.87, 95% CI 0.39-1.99) and an increased risk of SCC (OR 1.58, 95% CI 0.93-2.69). Conclusion Our findings suggest that allergies and atopy may influence risk of early onset BCC and SCC, and that effects may be gender specific. Impact A deeper understanding of the immune mechanisms underlying allergies and atopy may provide new routes of preventing keratinocyte cancer. PMID:25670807

The role of epithelial-mesenchymal transition in squamous cell carcinoma of the oral cavity.

PubMed

Zidar, Nina; Boštjančič, Emanuela; Malgaj, Marija; Gale, Nina; Dovšak, Tadej; Didanovič, Vojko

2018-02-01

Epithelial-mesenchymal transition (EMT) has emerged as a possible mechanism of cancer metastasizing, but strong evidence for EMT involvement in human cancer is lacking. Our aim was to compare oral spindle cell carcinoma (SpCC) as an example of EMT with oral conventional squamous cell carcinoma (SCC) with and without nodal metastases to test the hypothesis that EMT contributes to metastasizing in oral SCC. Thirty cases of oral SCC with and without nodal metastasis and 15 cases of SpCC were included. Epithelial (cytokeratin, E-cadherin), mesenchymal (vimentin, N-cadherin), and stem cell markers (ALDH-1, CD44, Nanog, Sox-2) and transcription repressors (Snail, Slug, Twist) were analyzed immunohistochemically. We also analyzed the expression of microRNAs miR-141, miR-200 family, miR-205, and miR-429. SpCC exhibited loss of epithelial markers and expression of mesenchymal markers or coexpression of both up-regulation of transcription repressors and down-regulation of the investigated microRNAs. SCC showed only occasional focal expression of mesenchymal markers at the invasive front. No other differences were observed between SCC with and without nodal metastases except for a higher expression of ALDH-1 in SCC with metastases. Our results suggest that SpCC is an example of true EMT but do not support the hypothesis that EMT is involved in metastasizing of conventional SCC. Regarding oral SCC progression and metastasizing, we have been facing a shift from the initial enthusiasm for the EMT concept towards a more critical approach with "EMT-like" and "partial EMT" concepts. The real question, though, is, is there no EMT at all?

Fluorescence photon migration techniques for the on-farm measurement of somatic cell count in fresh cow's milk

NASA Astrophysics Data System (ADS)

Khoo, Geoffrey; Kuennemeyer, Rainer; Claycomb, Rod W.

2005-04-01

Currently, the state of the art of mastitis detection in dairy cows is the laboratory-based measurement of somatic cell count (SCC), which is time consuming and expensive. Alternative, rapid, and reliable on-farm measurement methods are required for effective farm management. We have investigated whether fluorescence lifetime measurements can determine SCC in fresh, unprocessed milk. The method is based on the change in fluorescence lifetime of ethidium bromide when it binds to DNA from the somatic cells. Milk samples were obtained from a Fullwood Merlin Automated Milking System and analysed within a twenty-four hour period, over which the SCC does not change appreciably. For reference, the milk samples were also sent to a testing laboratory where the SCC was determined by traditional methods. The results show that we can quantify SCC using the fluorescence photon migration method from a lower bound of 4x105 cells mL-1 to an upper bound of 1 x 107 cells mL-1. The upper bound is due to the reference method used while the cause of the lower boundary is unknown, yet.

Systematical analysis of cutaneous squamous cell carcinoma network of microRNAs, transcription factors, and target and host genes.

PubMed

Wang, Ning; Xu, Zhi-Wen; Wang, Kun-Hao

2014-01-01

MicroRNAs (miRNAs) are small non-coding RNA molecules found in multicellular eukaryotes which are implicated in development of cancer, including cutaneous squamous cell carcinoma (cSCC). Expression is controlled by transcription factors (TFs) that bind to specific DNA sequences, thereby controlling the flow (or transcription) of genetic information from DNA to messenger RNA. Interactions result in biological signal control networks. Molecular components involved in cSCC were here assembled at abnormally expressed, related and global levels. Networks at these three levels were constructed with corresponding biological factors in term of interactions between miRNAs and target genes, TFs and miRNAs, and host genes and miRNAs. Up/down regulation or mutation of the factors were considered in the context of the regulation and significant patterns were extracted. Participants of the networks were evaluated based on their expression and regulation of other factors. Sub-networks with two core TFs, TP53 and EIF2C2, as the centers are identified. These share self-adapt feedback regulation in which a mutual restraint exists. Up or down regulation of certain genes and miRNAs are discussed. Some, for example the expression of MMP13, were in line with expectation while others, including FGFR3, need further investigation of their unexpected behavior. The present research suggests that dozens of components, miRNAs, TFs, target genes and host genes included, unite as networks through their regulation to function systematically in human cSCC. Networks built under the currently available sources provide critical signal controlling pathways and frequent patterns. Inappropriate controlling signal flow from abnormal expression of key TFs may push the system into an incontrollable situation and therefore contributes to cSCC development.

Identification of TRA2B-DNAH5 fusion as a novel oncogenic driver in human lung squamous cell carcinoma

PubMed Central

Li, Fei; Fang, Zhaoyuan; Zhang, Jian; Li, Chen; Liu, Hongyan; Xia, Jufeng; Zhu, Hongwen; Guo, Chenchen; Qin, Zhen; Li, Fuming; Han, Xiangkun; Wang, Yuetong; Feng, Yan; Wang, Ye; Zhang, Wenjing; Wang, Zuoyun; Jin, Yujuan; Sun, Yihua; Wei, Wenyi; Zeng, Rong; Chen, Haiquan; Ji, Hongbin

2016-01-01

Lung squamous cell carcinoma (SCC) is one of the major subtypes of lung cancer. Our current knowledge of oncogenic drivers in this specific subtype of lung cancer is largely limited compared with lung adenocarcinoma (ADC). Through exon array analyses, molecular analyses and functional studies, we here identify the TRA2B-DNAH5 fusion as a novel oncogenic driver in lung SCC. We found that this gene fusion occurs exclusively in lung SCC (3.1%, 5/163), but not in lung ADC (0/119). Through mechanistic studies, we further revealed that this TRA2B-DNAH5 fusion promotes lung SCC malignant progression through regulating a SIRT6-ERK1/2-MMP1 signaling axis. We show that inhibition of ERK1/2 activation using selumetinib efficiently inhibits the growth of lung SCC with TRA2B-DNAH5 fusion expression. These findings improve our current knowledge of oncogenic drivers in lung SCC and provide a potential therapeutic strategy for lung SCC patients with TRA2B-DNAH5 fusion. PMID:27670699

Associations of herd- and cow-level factors, cow lying behavior, and risk of elevated somatic cell count in free-stall housed lactating dairy cows.

PubMed

Watters, M E Alexandrea; Meijer, Karin M A; Barkema, Herman W; Leslie, Kenneth E; von Keyserlingk, Marina A G; Devries, Trevor J

2013-09-01

Recent evidence suggests that the risk of intramammary infection in dairy cows is related to lying patterns. The objectives of this study were to quantify the standing and lying behavior of dairy cows milked 3×/d, determine the cow- and herd-level factors associated with these behaviors, and relate these findings to the risk of an elevated somatic cell count (SCC). Five commercial free-stall dairy herds in Eastern Ontario, milking 3×/d, were enrolled in a longitudinal study. Forty Holstein-Friesian cows/herd were randomly selected as focal animals based on days in milk (<200 d) and SCC (<100,000 cells/mL). Farms were followed for 4, 5-week periods. Individual-cow SCC was recorded at the beginning of each period and end of the final period. Elevated SCC (eSCC) was used as an indicator of subclinical mastitis. A new incident eSCC was defined as an individual cow that started the period with a SCC <100,000 cells/mL but whose next SCC exceeded 200,000 cells/mL. Lying behavior was recorded 5d after each milk sampling using data loggers. For these 5d, individual milking times and feeding times were also recorded. On d1 of each recording period 2 trained observers scored focal cows for hygiene and lameness. Throughout the course of the study, cows averaged 11.2h/d of lying time, split into 8.6 lying bouts/d that were on average 84.6 min in length. Later lactation cows had longer daily lying times that were split into fewer lying bouts of longer duration than cows earlier in lactation. Lame cows had longer daily lying times and lying bout durations than non-lame cows. Cows with greater milk yield had lower lying times than lower producing cows. Average post-milking standing time across the study herds was 103 min. Manipulation of feed (feed delivery or push-up) by the stockperson, in the hour before milking or shortly thereafter, resulted in the longest post-milking standing times. Over the study period, 48 new eSCC were detected, resulting in a mean herd incidence rate of 0.91 eSCC/cow-year at risk for all study herds. A non-linear relationship between post-milking standing time and eSCC incidence was found; compared to those cows that lie down <90 min after milking, cows that lie down for the first time >90 min after milking had a lower risk of acquiring a new eSCC. The risk of experiencing an eSCC was also increased in multiparous cows, and in those cows with a higher SCC at the beginning of the study. These results indicate that management practices that promote post-milking standing time, such as the manipulation of feed delivery around milking times, should be encouraged to reduce the risk of cows experiencing new eSCC. Copyright © 2013 Elsevier B.V. All rights reserved.

Incidence of cutaneous squamous cell carcinoma in a New Zealand population of chronic lymphocytic leukaemia patients.

PubMed

Hock, B D; McIntosh, N D; McKenzie, J L; Pearson, J F; Simcock, J W; MacPherson, S A

2016-12-01

Chronic lymphocytic leukaemia (CLL) is associated with an increased incidence and aggressiveness of skin cancers, particularly cutaneous squamous cell carcinoma (cSCC), but little is known about cSCC incidence in Australasian CLL patients. In this retrospective study, we analysed the incidence of cSCC in patients seen at a tertiary hospital in New Zealand (NZ). We retrospectively assessed the clinical history and histology data of CLL patients (n = 371) who presented to the Haematology Department, Christchurch Hospital, NZ during the period 1996-2015. Baseline characteristics, incidence of second cancers, treatment details and overall survival were analysed. During follow-up (median = 11.8 years), 221 second cancers were recorded in 88 patients. Of these cancers, 185 were cSCC, removed from 61 patients. In 56% of these patients, >1 cSCC was removed, and the majority of cSCC occurred following the treatment for CLL. The cumulative incidence of a first cSCC was 11% at 5 years, whereas the cumulative incidence of a subsequent cSCC was 88% at 5 years. The incidence of cSCC in male patients was threefold higher than that reported for the general NZ population. NZ CLL patients have a high incidence of cSCC relative to the levels observed in the general population, which are themselves among the highest in the world. The careful monitoring of CLL patients is warranted, particularly those who have a progressive disease or have had a first cSCC removed. © 2016 Royal Australasian College of Physicians.

Cutaneous Squamous Cell Carcinoma.

PubMed

Parekh, Vishwas; Seykora, John T

2017-09-01

Cutaneous squamous cell carcinoma (cSCC) is a malignant neoplasm of the skin characterized by an aberrant proliferation of keratinocytes. Cutaneous SCC is the second most common malignancy globally, and usually arises in the chronically sun-damaged skin of elderly white individuals. From a pathologist's perspective, it is important to differentiate cSCC from the benign and reactive squamoproliferative lesions and identify the high-risk features associated with aggressive tumor behavior. In this article, we provide an up-to-date overview of cSCC along with its precursor lesions and important histologic variants, with a particular emphasis on the histopathologic features and molecular pathogenesis. Copyright © 2017 Elsevier Inc. All rights reserved.

Chl1 DNA helicase and Scc2 function in chromosome condensation through cohesin deposition.

PubMed

Shen, Donglai; Skibbens, Robert V

2017-01-01

Chl1 DNA helicase promotes sister chromatid cohesion and associates with both the cohesion establishment acetyltransferase Eco1/Ctf7 and the DNA polymerase processivity factor PCNA that supports Eco1/Ctf7 function. Mutation in CHL1 results in precocious sister chromatid separation and cell aneuploidy, defects that arise through reduced levels of chromatin-bound cohesins which normally tether together sister chromatids (trans tethering). Mutation of Chl1 family members (BACH1/BRIP/FANCJ and DDX11/ChlR1) also exhibit genotoxic sensitivities, consistent with a role for Chl1 in trans tethering which is required for efficient DNA repair. Chl1 promotes the recruitment of Scc2 to DNA which is required for cohesin deposition onto DNA. There is limited evidence, however, that Scc2 also directs the deposition onto DNA of condensins which promote tethering in cis (intramolecular DNA links). Here, we test the ability of Chl1 to promote cis tethering and the role of both Chl1 and Scc2 to promote condensin recruitment to DNA. The results reveal that chl1 mutant cells exhibit significant condensation defects both within the rDNA locus and genome-wide. Importantly, chl1 mutant cell condensation defects do not result from reduced chromatin binding of condensin, but instead through reduced chromatin binding of cohesin. We tested scc2-4 mutant cells and similarly found no evidence of reduced condensin recruitment to chromatin. Consistent with a role for Scc2 specifically in cohesin deposition, scc2-4 mutant cell condensation defects are irreversible. We thus term Chl1 a novel regulator of both chromatin condensation and sister chromatid cohesion through cohesin-based mechanisms. These results reveal an exciting interface between DNA structure and the highly conserved cohesin complex.

Chl1 DNA helicase and Scc2 function in chromosome condensation through cohesin deposition

PubMed Central

Shen, Donglai

2017-01-01

Chl1 DNA helicase promotes sister chromatid cohesion and associates with both the cohesion establishment acetyltransferase Eco1/Ctf7 and the DNA polymerase processivity factor PCNA that supports Eco1/Ctf7 function. Mutation in CHL1 results in precocious sister chromatid separation and cell aneuploidy, defects that arise through reduced levels of chromatin-bound cohesins which normally tether together sister chromatids (trans tethering). Mutation of Chl1 family members (BACH1/BRIP/FANCJ and DDX11/ChlR1) also exhibit genotoxic sensitivities, consistent with a role for Chl1 in trans tethering which is required for efficient DNA repair. Chl1 promotes the recruitment of Scc2 to DNA which is required for cohesin deposition onto DNA. There is limited evidence, however, that Scc2 also directs the deposition onto DNA of condensins which promote tethering in cis (intramolecular DNA links). Here, we test the ability of Chl1 to promote cis tethering and the role of both Chl1 and Scc2 to promote condensin recruitment to DNA. The results reveal that chl1 mutant cells exhibit significant condensation defects both within the rDNA locus and genome-wide. Importantly, chl1 mutant cell condensation defects do not result from reduced chromatin binding of condensin, but instead through reduced chromatin binding of cohesin. We tested scc2-4 mutant cells and similarly found no evidence of reduced condensin recruitment to chromatin. Consistent with a role for Scc2 specifically in cohesin deposition, scc2-4 mutant cell condensation defects are irreversible. We thus term Chl1 a novel regulator of both chromatin condensation and sister chromatid cohesion through cohesin-based mechanisms. These results reveal an exciting interface between DNA structure and the highly conserved cohesin complex. PMID:29186203

Less aggressive disease in patients with primary squamous cell carcinomas of the thyroid gland and coexisting lymphocytic thyroiditis.

PubMed

Asik, Mehmet; Binnetoglu, Emine; Sen, Hacer; Gunes, Fahri; Muratli, Asli; Kankaya, Duygu; Uysal, Fatma; Sahin, Mustafa; Ukinc, Kubilay

2015-01-01

Primary squamous cell carcinoma (SCC) of the thyroid gland is extremely rare. Infrequently, primary SCC of the thyroid gland is accompanied by other thyroid diseases such as Hashimoto's thyroiditis (HT). Recently, studies have demonstrated that differentiated thyroid cancer with coexisting HT has a better prognosis. However, the prognosis of patients with primary SCC of the thyroid gland and coexistent HT has not been clearly identified. We compared the clinical characteristics and disease stages of patients with primary SCC with and without lymphocytic thyroiditis (LT). We reviewed reports of primary SCC of the thyroid gland published in the English literature. We identified 46 papers that included 17 cases of primary SCC of the thyroid gland with LT and 77 cases of primary SCC of the thyroid gland without LT. Lymph node metastasis and local invasion rates did not differ between these two groups. Distant metastases were absent in patients with LT, and were observed in 13 (16.9%) patients without LT. A greater proportion of patients without LT had advanced stage disease (stage IV A-B-C) than patients with LT (p < 0.05). Patients with primary SCC of the thyroid gland and coexisting LT had lower tumour-node-metastasis stage and frequency of distant metastasis than those without LT. Lymphocytic infiltration in patients with SCC appears to limit tumour growth and distant metastases.

The current role of in vivo reflectance confocal microscopy within the continuum of actinic keratosis and squamous cell carcinoma: a systematic review.

PubMed

Nguyen, Kim P; Peppelman, Malou; Hoogedoorn, Lisa; Van Erp, Piet E J; Gerritsen, Marie-Jeanne P

2016-12-01

Clinical differentiation between actinic keratosis (AK), squamous cell carcinoma (SCC) in situ, and invasive SCC and its variants may be difficult. Reflectance confocal microscopy (RCM) is a non-invasive technique for in vivo skin imaging. To explicate the diagnostic and monitoring use of RCM within the spectrum of AK and SCC, and evaluate the accuracy of RCM for these diagnoses relative to histopathology. A systematic literature search was performed in PubMed, EMBASE, the Cochrane Library, and Web of Science databases. The quality was assessed using the STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) checklist. Twenty-five eligible studies were included. Different diagnostic RCM features have been described for AK, actinic cheilitis (AC), erythroplasia of Queyrat, Bowen disease, invasive SCC, and keratoacanthoma (KA). The overall range of sensitivity and specificity of RCM for the diagnosis of SCC, AK, SCC in situ, and KA was 79-100% and 78-100%, respectively. The current literature describes the use of RCM for diagnosing AK, AC, erythroplasia of Queyrat, Bowen disease, invasive SCC, and KA, as well as for monitoring treatments of AK, with good accuracy. Unfortunately, studies with high methodological quality are lacking. Pre-treatment of hyperkeratotic lesions and uniform definitions of RCM features are required to simplify the differentiation between AKs, SCC in situ, and SCC and its variants in clinical practice.

Effect of Adipose-Derived Stem Cells on Head and Neck Squamous Cell Carcinoma.

PubMed

Danan, Deepa; Lehman, Christine E; Mendez, Rolando E; Langford, Brian; Koors, Paul D; Dougherty, Michael I; Peirce, Shayn M; Gioeli, Daniel G; Jameson, Mark J

2018-05-01

Objective Patients with head and neck squamous cell carcinoma (HNSCC) have significant wound-healing difficulties. While adipose-derived stem cells (ASCs) facilitate wound healing, ASCs may accelerate recurrence when applied to a cancer field. This study evaluates the impact of ASCs on HNSCC cell lines in vitro and in vivo. Study Design In vitro experiments using HNSCC cell lines and in vivo mouse experiments. Setting Basic science laboratory. Subjects and Methods Impact of ASCs on in vitro proliferation, survival, and migration was assessed using 8 HNSCC cell lines. One cell line was used in a mouse orthotopic xenograft model to evaluate in vivo tumor growth in the presence and absence of ASCs. Results Addition of ASCs did not increase the number of HNSCC cells. In clonogenic assays to assess cell survival, addition of ASCs increased colony formation only in SCC9 cells (maximal effect 2.3-fold, P < .02) but not in other HNSCC cell lines. In scratch assays to assess migration, fluorescently tagged ASCs did not migrate appreciably and did not increase the rate of wound closure in HNSCC cell lines. Addition of ASCs to HNSCC xenografts did not increase tumor growth. Conclusion Using multiple in vitro and in vivo approaches, ASCs did not significantly stimulate HNSCC cell proliferation or migration and increased survival in only a single cell line. These findings preliminarily suggest that the use of ASCs may be safe in the setting of HNSCC but that further investigation on the therapeutic use of ASCs in the setting of HNSCC is needed.

Electrochemotherapy with cisplatin or bleomycin in head and neck squamous cell carcinoma: Improved effectiveness of cisplatin in HPV-positive tumors.

PubMed

Prevc, Ajda; Niksic Zakelj, Martina; Kranjc, Simona; Cemazar, Maja; Scancar, Janez; Kosjek, Tina; Strojan, Primoz; Sersa, Gregor

2018-06-06

Human papillomavirus (HPV) is an important etiological factor in head and neck squamous cell carcinomas (SCCs). Standard treatment of HPV-positive tumors with platinum-based radio(chemo)therapy results in a better outcome than in HPV-negative tumors. Electrochemotherapy is becoming an increasingly recognized mode of treatment in different cancers; thus, its use in the management of head and neck SCC is of considerable interest. However, response to electrochemotherapy according to HPV status of the tumors has not been evaluated yet. Thus, our aim was to compare the effect of electrochemotherapy with cisplatin or bleomycin between HPV-negative and HPV-positive human pharyngeal SCC derived cell lines and tumor models. HPV-positive cells and tumors were found to be more sensitive to electrochemotherapy with cisplatin than HPV-negative ones, whereas sensitivity to electrochemotherapy with bleomycin was similar irrespective of the HPV status. The higher sensitivity of HPV-positive cells and tumors to electrochemotherapy with cisplatin is likely due to the higher level and slower repair of DNA damage. In HPV-negative tumors, a higher number of complete responses was recorded after bleomycin-based rather than cisplatin-based electrochemotherapy, while in HPV-positive tumors electrochemotherapy with cisplatin was more effective. Copyright © 2018. Published by Elsevier B.V.

Treating cutaneous squamous cell carcinoma using ALA PLGA nanoparticle-mediated photodynamic therapy in a mouse model

NASA Astrophysics Data System (ADS)

Wang, Xiaojie; Shi, Lei; Tu, Qingfeng; Wang, Hongwei; Zhang, Haiyan; Wang, Peiru; Zhang, Linglin; Huang, Zheng; Wang, Xiuli; Zhao, Feng; Luan, Hansen

2015-03-01

Background: Squamous cell carcinoma (SCC) is a common skin cancer and its treatment is still difficult. The aim of this study was to evaluate the effectiveness of nanoparticle (NP)-assisted ALA delivery for topical photodynamic therapy (PDT) of cutaneous SCC. Methods: UV-induced cutaneous SCCs were established in hairless mice. ALA loaded polylactic-co-glycolic acid (PLGA) NPs were prepared and characterized. The kinetics of ALA PLGA NPs-induced protoporphyrin IX (PpIX) fluorescence in SCCs, therapeutic efficacy of ALA NP-mediated PDT, and immune responses were examined. Results: PLGA NPs could enhance PpIX production in SCC. ALA PLGA NP mediated topical PDT was more effective than free ALA of the same concentration in treating cutaneous SCC. Conclusion: PLGA NPs provide a promising strategy for delivering ALA in topical PDT of cutaneous SCC.

Age and clear eyes are associated with an increased risk of cutaneous squamous cell carcinomas in vemurafenib-treated melanoma patients.

PubMed

Herms, Florian; Kramkimel, Nora; Regnier-Rosencher, Elodie; Carlotti, Agnès; Chanal, Johan; Boitier, Françoise; Aractingi, Selim; Dupin, Nicolas; Avril, Marie-Françoise

2016-10-01

Cutaneous squamous cell carcinoma (cSCC) is a frequent side-effect of vemurafenib treatment. The main aim of this study was to identify the clinical risk factors associated with the development of cSCC in melanoma patients treated with vemurafenib. We carried out a retrospective study, including 63 consecutive melanoma patients treated with vemurafenib for BRAF-mutant metastatic melanoma in an oncodermatological department. Clinical and follow-up data were collected and analysed, and a comparison of the subgroups who did and did not develop cSCC was performed. A total of 42.9% of patients (n=27) treated with vemurafenib developed one or more cSCC. Patients with cSCC were significantly older (P=0.01). Clear eyes were also associated with a higher risk of developing cSCC (odds ratio=3.50; 95% confidence interval: 1.08-12.43). Three patients developed cSCC more than 1 year after the initiation of treatment (12, 16 and 18 months, respectively). Clinicians should be vigilant in older patients undergoing vemurafenib therapy as well as patients with clear eyes as they seem to be at increased risk of developing cSCC, even late after the initiation of treatment.

Risk of cutaneous squamous cell carcinoma after treatment of basal cell carcinoma with vismodegib.

PubMed

Bhutani, Tina; Abrouk, Michael; Sima, Camelia S; Sadetsky, Natalia; Hou, Jeannie; Caro, Ivor; Chren, Mary-Margaret; Arron, Sarah T

2017-10-01

Vismodegib is a first-in-class agent targeting the hedgehog signaling pathway for treatment of patients with locally advanced basal cell carcinoma (BCC) and metastatic BCC. There have been concerns about the development of squamous cell carcinoma (SCC) in patients treated with this drug. We sought to determine whether treatment with vismodegib is associated with an increase in the risk of cutaneous SCC. In this retrospective cohort study, patients treated with vismodegib as part of phase I and II clinical studies were compared with participants from the University of California, San Francisco, Nonmelanoma Skin Cancer Cohort who received standard therapy for primary BCC. In total, 1675 patients were included in the analysis, and the development of SCC after vismodegib exposure was assessed. The use of vismodegib was not associated with an increased risk of subsequent development of SCC (adjusted hazard ratio, 0.57; 95% confidence interval, 0.28-1.16). Covariates including age, sex, history of previous nonmelanoma skin cancer, and number of visits per year were significantly associated with the development of SCC. A limitation of the study was that a historic control cohort was used as a comparator. Vismodegib was not associated with an increased risk of subsequent SCC when compared with standard surgical treatment of BCC. Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Genetic variation in SIRT1 affects susceptibility of lung squamous cell carcinomas in former uranium miners from the Colorado plateau

PubMed Central

Leng, Shuguang; Picchi, Maria A.; Liu, Yushi; Thomas, Cynthia L.; Willis, Derall G.; Bernauer, Amanda M.; Carr, Teara G.; Mabel, Padilla T.; Han, Younghun; Amos, Christopher I.; Lin, Yong; Stidley, Christine A.; Gilliland, Frank D.; Jacobson, Marty R.; Belinsky, Steven A.

2013-01-01

Epidemiological studies of underground miners suggested that occupational exposure to radon causes lung cancer with squamous cell carcinoma (SCC) as the predominant histological type. However, the genetic determinants for susceptibility of radon-induced SCC in miners are unclear. Double-strand breaks induced by radioactive radon daughters are repaired primarily by non-homologous end joining (NHEJ) that is accompanied by the dynamic changes in surrounding chromatin, including nucleosome repositioning and histone modifications. Thus, a molecular epidemiological study was conducted to assess whether genetic variation in 16 genes involved in NHEJ and related histone modification affected susceptibility for SCC in radon-exposed former miners (267 SCC cases and 383 controls) from the Colorado plateau. A global association between genetic variation in the haplotype block where SIRT1 resides and the risk for SCC in miners (P = 0.003) was identified. Haplotype alleles tagged by the A allele of SIRT1 rs7097008 were associated with increased risk for SCC (odds ratio = 1.69, P = 8.2×10−5) and greater survival in SCC cases (hazard ratio = 0.79, P = 0.03) in miners. Functional validation of rs7097008 demonstrated that the A allele was associated with reduced gene expression in bronchial epithelial cells and compromised DNA repair capacity in peripheral lymphocytes. Together, these findings substantiate genetic variation in SIRT1 as a risk modifier for developing SCC in miners and suggest that SIRT1 may also play a tumor suppressor role in radon-induced cancer in miners. PMID:23354305

Correlation between standard plate count and somatic cell count milk quality results for Wisconsin dairy producers.

PubMed

Borneman, Darand L; Ingham, Steve

2014-05-01

The objective of this study was to determine if a correlation exists between standard plate count (SPC) and somatic cell count (SCC) monthly reported results for Wisconsin dairy producers. Such a correlation may indicate that Wisconsin producers effectively controlling sanitation and milk temperature (reflected in low SPC) also have implemented good herd health management practices (reflected in low SCC). The SPC and SCC results for all grade A and B dairy producers who submitted results to the Wisconsin Department of Agriculture, Trade, and Consumer Protection, in each month of 2012 were analyzed. Grade A producer SPC results were less dispersed than grade B producer SPC results. Regression analysis showed a highly significant correlation between SPC and SCC, but the R(2) value was very small (0.02-0.03), suggesting that many other factors, besides SCC, influence SPC. Average SCC (across 12 mo) for grade A and B producers decreased with an increase in the number of monthly SPC results (out of 12) that were ≤ 25,000 cfu/mL. A chi-squared test of independence showed that the proportion of monthly SCC results >250,000 cells/mL varied significantly depending on whether the corresponding SPC result was ≤ 25,000 or >25,000 cfu/mL. This significant difference occurred in all months of 2012 for grade A and B producers. The results suggest that a generally consistent level of skill exists across dairy production practices affecting SPC and SCC. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Barium inhibits arsenic-mediated apoptotic cell death in human squamous cell carcinoma cells.

PubMed

Yajima, Ichiro; Uemura, Noriyuki; Nizam, Saika; Khalequzzaman, Md; Thang, Nguyen D; Kumasaka, Mayuko Y; Akhand, Anwarul A; Shekhar, Hossain U; Nakajima, Tamie; Kato, Masashi

2012-06-01

Our fieldwork showed more than 1 μM (145.1 μg/L) barium in about 3 μM (210.7 μg/L) arsenic-polluted drinking well water (n = 72) in cancer-prone areas in Bangladesh, while the mean concentrations of nine other elements in the water were less than 3 μg/L. The types of cancer include squamous cell carcinomas (SCC). We hypothesized that barium modulates arsenic-mediated biological effects, and we examined the effect of barium (1 μM) on arsenic (3 μM)-mediated apoptotic cell death of human HSC-5 and A431 SCC cells in vitro. Arsenic promoted SCC apoptosis with increased reactive oxygen species (ROS) production and JNK1/2 and caspase-3 activation (apoptotic pathway). In contrast, arsenic also inhibited SCC apoptosis with increased NF-κB activity and X-linked inhibitor of apoptosis protein (XIAP) expression level and decreased JNK activity (antiapoptotic pathway). These results suggest that arsenic bidirectionally promotes apoptotic and antiapoptotic pathways in SCC cells. Interestingly, barium in the presence of arsenic increased NF-κB activity and XIAP expression and decreased JNK activity without affecting ROS production, resulting in the inhibition of the arsenic-mediated apoptotic pathway. Since the anticancer effect of arsenic is mainly dependent on cancer apoptosis, barium-mediated inhibition of arsenic-induced apoptosis may promote progression of SCC in patients in Bangladesh who keep drinking barium and arsenic-polluted water after the development of cancer. Thus, we newly showed that barium in the presence of arsenic might inhibit arsenic-mediated cancer apoptosis with the modulation of the balance between arsenic-mediated promotive and suppressive apoptotic pathways.

Prognostic value of CD44 expression in penile squamous cell carcinoma: a pilot study.

PubMed

Minardi, Daniele; Lucarini, Guendalina; Filosa, Alessandra; Zizzi, Antonio; Simonetti, Oriana; Offidani, Anna Maria; d'Anzeo, Gianluca; Di Primio, Roberto; Montironi, Rodolfo; Muzzonigro, Giovanni

2012-10-01

Several studies have reported on the prognostic value of molecular markers for metastasis risk and survival in penile squamous cell carcinoma (SCC) patients. The usefulness of CD44 expression as such a marker has been studied in different tumors, but not in penile SCC. Our aim was to determine whether CD44 expression may serve as a prognostic marker for lymph node metastasis and survival in penile SCC patients. CD44 immunoistochemical expression was investigated in tissue specimens from 39 patients with penile SCC. CD44 cell positivity, staining intensity and distribution were analyzed and correlated with tumor stage, grade, lymph node status and disease-specific survival. CD44 expression was detected in epithelial cells of both intratumoral and normal tissues with different intensities and staining distributions. In normal tissues CD44 protein was mainly detected in cell membranes, whereas in the tumor compartments it was found in both the cell membranes and the cytoplasm. The intensities and percentages of CD44 expressing cells did not correlate with tumor stage and/or grade. Seventy-three percent of the patients with lymph node metastasis showed high intensities of CD44 staining, as compared to 44% of the patients without lymph node metastasis (P = 0.03). Lymph node-positive patients showed both cytoplasmic and membranous CD44 expression. High CD44 expression was found to be significantly correlated with a decreased 5 year overall survival (P = 0.01). CD44 levels and patterns of expression can be considered as markers for penile SCC aggressiveness and, in addition, may serve as predictive markers for lymph node metastasis, also in patients with clinically negative lymph nodes. CD44 expression may provide prognostic information for penile SCC patients, next to classical clinical-pathological factors.

Combined oncolytic virotherapy with herpes simplex virus for oral squamous cell carcinoma.

PubMed

Ogawa, Fumi; Takaoka, Hiroo; Iwai, Soichi; Aota, Keiko; Yura, Yoshiaki

2008-01-01

The effect of dual infection with herpes simplex virus type 1 (HSV-1) mutants on human oral squamous cell carcinoma (SCC) cells was examined. Human oral SCC cells were infected with gamma1(34.5) gene-deficient HSV-1 R849 and HSV-1 HF that has multiple mutations and induces cell fusion. Cell viability was measured by LDH release assay. Athymic mice were injected with oral SCC cells into the buccal region to induce subcutaneous tumors. Oral SCC cells were infected with R849, followed by infection with R849 or HF. Virus production was elevated by both strains of HSV-1. Although the release of LDH from R849-infected cells was increased by secondary infection with R849 or HF, the effect of HF was more remarkable. When nude mouse tumors were treated with R849, HF, R849+R849, or R849+HF, treatment with R849+HF was the most effective. These results suggest that fusion-inducing virus HF enhances the oncolytic ability of gamma1(34.5) gene-deficient HSV-1 and provides a rationale for using fusogenic viruses as enhancing agents

Clear-cell differentiation and lymphatic invasion, but not the revised TNM classification, predict lymph node metastases in pT1 penile cancer: a clinicopathologic study of 76 patients from a low incidence area.

PubMed

Mannweiler, Sebastian; Sygulla, Stephan; Tsybrovskyy, Oleksiy; Razmara, Yas; Pummer, Karl; Regauer, Sigrid

2013-10-01

Prediction of lymph node (LN) metastases in penile invasive cancer relies on clinical features and histologic characteristics of the primary tumor. Correct prediction, however, is difficult, as only 50% patients undergoing lymphadenectomies will have LN metastases. In 2009, the tumor, nodes, metastases (TNM) classification for staging of early penile cancers was revised. We tested the predictive accuracy of the revised TNM classification in a low incidence area for penile carcinoma. The presence of LN metastases in 76 men with pT1 penile cancers was correlated with the 2009 TNM subclassification, which is based on a combined evaluation of tumor grade and lymphatic invasion, but also with individual parameters, such as histologic grade, lymphatic invasion, perineural invasion, invasion depth, growth pattern and human papilloma virus (HPV) status. 76pT1 penile cancers were reclassified into 31pT1a squamous cell carcinomas (SCC) and 45pT1b (41 SCC; 4 clear-cell carcinomas); 12/22 men (55%; 8 SCC, 4 clear-cell carcinomas) undergoing lymphadenectomy for enlarged inguinal lymph nodes had metastases, 54 patients without enlarged LN and lymphadenectomies had no LN metastases during follow-up of median 47 months. Statistically, clear cell differentiation of the primary carcinoma was highly associated with metastases (100% clear-cell carcinomas vs. 11% SCC) and poor survival (50% vs. 5.5%). Among conventional SCC, only lymphatic invasion showed a highly significant association with metastases with 100% specificity. The 2009 TNM classification, tumor grade alone, perineural invasion, growth pattern, invasion depth or HPV status could not predict LN status. Lymphadenectomy for enlarged LN resulted in 100% sensitivity and 42% predictive probability for identifying metastases and a 16% false positive rate. Statistically, survival correlated significantly with clear-cell differentiation and with lymphatic invasion in both clear-cell carcinomas and conventional SCC. Penile clear-cell carcinomas are more aggressive cancers than SCC. Our observation suggests a benefit of a prophylactic lymphadenectomy for patients with clear-cell carcinomas. Among conventional SCC, only lymphatic invasion predicted LN metastases. Neither tumor grade alone nor perineural invasion, growth pattern, depth of invasion, and subgrouping according to the revised TNM classification correlated with metastases. Clinical evaluation of the LN status was superior to histologic risk stratification. Copyright © 2013 Elsevier Inc. All rights reserved.

Expression of matrix metalloproteinase-13 and Ki-67 in nonmelanoma skin cancer in xeroderma pigmentosum and non-xeroderma pigmentosum.

PubMed

El-Hawary, Amira K; Yassin, Eman; Khater, Ashraf; Abdelgaber, Soheir

2013-02-01

Xeroderma pigmentosum (XP) is a heterogenous group of genetic diseases in which basal cell carcinoma (BCC) is the most common nonmelanoma skin cancer (NMSC) followed by squamous cell carcinoma (SCC). The aim of this study was to investigate the expression of matrix metalloproteinase (MMP)-13 and Ki-67 in SCC and BCC from patients with and without XP to elucidate their roles in the pathogenesis of these highly aggressive tumors in patients with XP. Immunolabeling using MMP-13 and Ki-67 antibodies was performed on tissue sections derived from skin biopsies of SCC and BCC of 15 patients with XP and 40 non-XP patients. There was no significant difference between XP and non-XP patients as regards MMP-13 expression by epithelial and stromal cells of SCC or BCC. Ki-67 expression in SCC and BCC of patients with XP was significantly higher than in non-XP patients. We concluded that the higher expression of Ki-67 in NMSC of patients with XP than of non-XP patients may reflect the growth and invasive capacity of these tumors in patients with XP. MMP-13 is expressed by tumor epithelial cells, stromal and inflammatory cells of NMSC of both XP and non-XP patients.

Oral cavity squamous cell carcinoma - characteristics and survival in aboriginal and non-aboriginal Western australians.

PubMed

Frydrych, A M; Slack-Smith, L M; Parsons, R; Threlfall, T

2014-01-01

Squamous cell carcinoma (SCC) is the most common type of malignancy affecting the oral cavity. While exposures to main risk factors for oral SCC such as smoking and alcohol use are higher amongst the Aboriginal people, little is known about oral cancer in this population. This study aimed to describe characteristics and survival of oral SCC in Aboriginal and non-Aboriginal Western Australians. All primary oral SCC cases reported to the Western Australian Cancer Registry (WACR) between 1990 and 1999 were analysed with respect to person characteristics including: date of birth, sex and indigenous status; and disease characteristics including: date of biopsy, disease stage and site as well as date of recurrence and date of death. Exclusion criteria included diagnosis not based on incisional or excisional biopsy, diagnosis other than oral SCC or a history of another malignant neoplasm. Aboriginal individuals were more likely to reside in rural areas. No statistically significant differences in oral SCC characteristics and survival were noted between Aboriginal and non-Aboriginal Western Australians. This study provides new information on person and disease characteristics of Aboriginal Western Australians diagnosed with oral SCC.

Squamous cell carcinoma-like and pox lesions occurring simultaneously in chorioallantoic membranes of chicken embryos inoculated with materials from squamous cell carcinoma and pox lesions in broiler chickens.

PubMed

Fallavena, L C; Rodrigues, N C; Moraes, H L; Salle, C T; da Silva, A B; Nascimento, V P; Rodrigues, O

1997-01-01

The finding of closely associated squamous cell carcinoma (SCC)-like lesions and pox lesions in chorioallantoic membranes (CAMs) inoculated with skin and palate samples taken from broilers is described. The samples were obtained from two broilers coming from different flocks that were not vaccinated against fowl pox. Both birds presented skin lesions, which were diagnosed in one bird as fowl pox, and in the other as SCC. After inoculation of CAMs with fresh tissues from both birds, histologic examination revealed, in all CAMs, lesions that were characteristic of fowl pox together with lesions consistent with those seen in the skin of broilers affected with SCC. This finding was unexpected and may shed some light on the etiology of SCC.

Human papillomavirus (HPV) and Oropharyngeal Squamous Cell Carcinoma (OP-SCC) of the Head and Neck: a Growing Epidemic

PubMed Central

Bauman, Jessica; Wirth, Lori

2015-01-01

Human papillomavirus (HPV) is now considered a major causative agent in oropharyngeal squamous cell carcinoma (OP-SCC). The incidence of HPV+ OP-SCC is increasing dramatically, is higher in men, and is now more common than cervical cancer in the United States. HPV+ OPSCCs usually present as locally advanced, stage IV cancers, requiring intensive treatment with surgery, chemotherapy, and/or radiation that can cause tremendous morbidity. HPV vaccination is predicted to prevent HPV+ OP-SCC because over 90% are caused by vaccine-type HPV. However, current vaccination rates are not yet high enough to be effective at preventing HPV-associated malignancies at a population level. PMID:27132327

Human polyomaviruses and incidence of cutaneous squamous cell carcinoma in the New Hampshire skin cancer study.

PubMed

Gossai, Anala; Waterboer, Tim; Hoen, Anne G; Farzan, Shohreh F; Nelson, Heather H; Michel, Angelika; Willhauck-Fleckenstein, Martina; Christensen, Brock C; Perry, Ann E; Pawlita, Michael; Karagas, Margaret R

2016-06-01

Squamous cell carcinoma (SCC) of the skin is a malignancy arising from epithelial keratinocytes. Experimental and epidemiologic evidence raise the possibility that human polyomaviruses (PyV) may be associated with the occurrence of SCC. To investigate whether the risk for SCC was associated with PyV infection, seropositivity to 10 PyV types was assessed following diagnosis in a population-based case-control study conducted in the United States. A total of 253 SCC cases and 460 age group and gender-matched controls were included. Antibody response against each PyV was measured using a multiplex serology-based glutathione S-transferase capture assay of recombinantly expressed VP1 capsid proteins. Odds ratios (OR) for SCC associated with seropositivity to each PyV type were estimated using logistic regression, with adjustment for potentially confounding factors. SCC cases were seropositive for a greater number of PyVs than controls (P = 0.049). Those who were JC seropositive had increased odds of SCC when compared to those who were JC seronegative (OR = 1.37, 95% CI: 0.98-1.90), with an increasing trend in SCC risk with increasing quartiles of seroreactivity (P for trend = 0.04). There were no clear associations between SCC risk and serostatus for other PyV types. This study provides limited evidence that infection with certain PyVs may be related to the occurrence of SCC in the general population of the United States. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Consequence of changing standards for somatic cell count on US Dairy Herd Improvement herds

USDA-ARS?s Scientific Manuscript database

Consequence of noncompliance with European Union (EU) and current US standards for somatic cell count (SCC) as well as SCC standards proposed by the National Milk Producers Federation was examined for US herds. Somatic cell scores (SCS) from 14,854 Dairy Herd Improvement (DHI) herds were analyzed. H...

Low-dose retinoic acid enhances in vitro invasiveness of human oral squamous-cell-carcinoma cell lines

PubMed Central

Uchida, D; Kawamata, H; Nakashiro, K; Omotehara, F; Hino, S; Hoque, M O; Begum, N-M; Yoshida, H; Sato, M; Fujimori, T

2001-01-01

Retinoids inhibit the proliferation of several types of tumour cells, and are used for patients with several malignant tumours. In this study, we examined the effect of retinoic acids (RAs) on the invasive potentials of the oral squamous cell carcinoma (SCC) cells, BHY and HNt. BHY cells expressed all of retinoid nuclear receptors (RARα, β, γ, and RXRα) and cytoplasmic retinoic acid binding proteins (CRABP1 and CRABP2). HNt cells lacked the expression of RARβ, but expressed other nuclear receptors and CRABPs. All-trans retinoic acid (ATRA) and 13-cis retinoic acid (13-cisRA) (10−6and 10−7M) inhibited the growth of the cells, but low-dose ATRA and 13-cisRA (10−8M) marginally affected the growth of the cells. Surprisingly, low-dose RAs enhanced the activity of tissue-type plasminogen activator (tPA), and activated pro-matrix metalloproteinases (proMMP2 and proMMP9). Activation of proMMP2 and proMMP9 was inhibited by aprotinin, a serine-proteinase, tPA inhibitor. Furthermore, low-dose RAs enhanced the in vitro invasiveness of BHY cells. These results indicate that low-dose RAs enhances the in vitro invasiveness of oral SCC cells via an activation of proMMP2 and proMMP9 probably mediated by the induction of tPA. © 2001 Cancer Research Campaign http://www.bjcancer.com PMID:11437413

Curcumin-cyclodextrin encapsulated chitosan nanoconjugates with enhanced solubility and cell cytotoxicity.

PubMed

Popat, Amirali; Karmakar, Surajit; Jambhrunkar, Siddharth; Xu, Chun; Yu, Chengzhong

2014-05-01

Curcumin (CUR), a naturally derived anti-cancer cocktail is arguably the most widely studied neutraceutical. Despite a lot of promises, it is yet to reach the market as an active anti-cancer formulation. In the present study, we have prepared highly soluble (3 mg/ml) CUR-γ-hydroxypropyl cyclodextrin (CUR-CD) hollow spheres. CUR-CD hollow spheres were prepared by a novel and scalable spray drying method. CUR-CD was then encapsulated into positively charged biodegradable chitosan (CUR-CD-CS) nanoparticles. The CUR-CD-CS nanoparticles were characterised by TEM, SEM, DLS, drug loading and in vitro release. We tested the efficacy of these CUR-CD-CS nanoparticles in SCC25 cell lines using MTT assay and investigated its cellular uptake mechanism. We also studied Oligo DNA loading in CUR-CD-CS nanoparticles and its delivery via confocal imaging and FACS analysis. Our results demonstrated that CUR-CD-CS nanoparticles showed superior in vitro release performance and higher cytotoxicity in SCC25 cell line amongst all tested formulations. The cytotoxicity results were corroborated by cell cycle analysis and apoptosis test, showing nearly 100% apoptotic cell death in the case of CUR-CD-CS nanoparticles. Compared to CS nanoparticles, CS-CD nanoformulation showed higher cellular delivery of Cy3-Oligo DNA which was tested quantitatively using flowcytometry analysis, indicating that CD not only enhanced CUR solubility but also boosted the cellular uptake. Our study shows that rationally designed bio-degradable natural biomaterials have great potential as next generation nano-carriers for hydrophobic drug delivery such as CUR with potential of dual drug-gene delivery. Copyright © 2014 Elsevier B.V. All rights reserved.

Coexistent Ampullary Squamous Cell Carcinoma with Adenocarcinoma of the Pancreatic Duct

PubMed Central

Pathak, Gayatri S.; Deshmukh, Sanjay D.; Yavalkar, Prasanna A.; Ashturkar, Amrut V.

2011-01-01

Primary squamous cell carcinoma (SCC) of ampulla has seldom been reported. However, metastatic SCC to ampulla of Vater is well known. We report a case of primary SCC of ampulla of Vater coexistent with well-differentiated adenocarcinoma of the distal pancreatic duct. A 50-year-old female presented with evidence of obstructive jaundice. Endoscopic retrograde cholangio-pancreatography revealed bulging papilla with ulcero-infiltrative growth at the ampulla of Vater. An initial endoscopic biopsy of the ampullary mass showed a well-differentiated SCC. The patient underwent Whipple's operation. Thorough sampling of the dilated portion of the pancreatic duct showed presence of well-differentiated adenocarcinoma of the distal pancreatic duct. Immunohistochemical study with synaptophysin and chromogranin was done with negative result, ruling out neuroendocrine differentiation. Also, a detailed clinical, endoscopic and radiological examination was carried out, that excluded the presence of primary SCC elsewhere. PMID:22064341

Alcohol intake is associated with increased risk of squamous cell carcinoma of the skin: three US prospective cohort studies

PubMed Central

Siiskonen, Satu; Han, Jiali; Li, Tricia; Cho, Eunyoung

2016-01-01

The association between alcohol intake and cutaneous squamous cell carcinoma (cSCC) is unclear. We studied the association between alcohol intake and incident invasive cSCC in three cohorts of women and men with repeated assessments of alcohol intake in the US. Information on alcohol intake was collected repeatedly during follow-up. Cumulative average of alcohol intakes was used. Multivariable Cox proportional hazards models with time-dependent exposure were used to estimate relative risks (RR) and 95% confidence intervals, followed by a meta-analysis. During a follow-up of 4,234,416 person-years, 2,938 cSCC were identified. Alcohol intake was associated with an increased risk of cSCC with a dose-response relationship. Each additional drink (12.8 gram of alcohol) per day was associated with a 22% increased risk of cSCC (RR 1.22, 95% confidence interval: 1.13 to 1.31). White wine consumption of ≥5 times/wk was associated with an increased risk of cSCC (RR 1.31, 95% confidence interval: 1.09 to 1.59). We found no increased risk of cSCC with other alcoholic beverages. The population attributable risk associated with alcohol intake of ≥20 grams/d was 3% of cSCCs. In conclusion, alcohol intake was associated with an elevated risk of cSCC. Among alcoholic beverages, white wine was associated with cSCC. PMID:27145335

Alcohol Intake is Associated with Increased Risk of Squamous Cell Carcinoma of the Skin: Three US Prospective Cohort Studies.

PubMed

Siiskonen, Satu; Han, Jiali; Li, Tricia; Cho, Eunyoung; Nijsten, Tamar; Qureshi, Abrar

2016-01-01

The association between alcohol intake and cutaneous squamous cell carcinoma (cSCC) is unclear. We studied the association between alcohol intake and incident invasive cSCC in three cohorts of women and men with repeated assessments of alcohol intake in the US. Information on alcohol intake was collected repeatedly during follow-up. Cumulative average of alcohol intakes was used. Multivariable Cox proportional hazards models with time-dependent exposure were used to estimate relative risks (RRs) and 95% confidence intervals, followed by a meta-analysis. During a follow-up of 4,234,416 person-years, 2,938 cSCC were identified. Alcohol intake was associated with an increased risk of cSCC with a dose-response relationship. Each additional drink (12.8 gram of alcohol) per day was associated with a 22% increased risk of cSCC (RR 1.22, 95% confidence interval: 1.13-1.31). White wine consumption of ≥5 times/wk was associated with an increased risk of cSCC (RR 1.31, 95% confidence interval: 1.09-1.59). We found no increased risk of cSCC with other alcoholic beverages. The population-attributable risk associated with alcohol intake of ≥20 grams/d was 3% of cSCCs. In conclusion, alcohol intake was associated with an elevated risk of cSCC. Among alcoholic beverages, white wine was associated with cSCC.

The role of immunosuppression in squamous cell carcinomas arising in seborrheic keratosis.

PubMed

Conic, Ruzica Z; Napekoski, Karl; Schuetz, Heidi; Piliang, Melissa; Bergfeld, Wilma; Atanaskova Mesinkovska, Natasha

2017-06-01

Seborrheic keratoses (SK) are common skin neoplasms considered to be benign. Reports of associated squamous cell carcinoma arising within seborrheic keratosis (SCC-SK) have been described. To describe the histopathologic characteristics of SCC-SK and identify predisposing factors in formation of these rare lesions. There were 162 cases of SCC-SK in a span of a decade (2003-2014). All of the histopathologic specimens and medical records were reviewed. Data from these patients were compared to a control group with seborrheic keratosis who were matched by age, sex, and location of lesion from the same time period (n = 162). SCC-SK has the classic histopathologic features of SK, such as hyperkeratosis, parakeratosis, papillomatosis, and pseudohorn cysts. The areas of squamous cell carcinoma were characterized by areas of squamous dysplasia (100%), hypogranulosis (79.6%), squamous eddies (79.6%), solar elastosis (80.9%), and brown pigmentation (59.9%). Patients with a history of immunosuppression had an increased risk for developing SCC-SK (19% vs 3%; P < .01), particularly when inhibition was transplant-associated (10% vs 0%; P < .01). This was a single center, retrospective study. SCC-SK occurs more often in elderly men with a history of immunosuppression associated with organ transplants. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Inactivation of the budding yeast cohesin loader Scc2 alters gene expression both globally and in response to a single DNA double strand break

PubMed Central

Lindgren, Emma; Hägg, Sara; Giordano, Fosco; Björkegren, Johan; Ström, Lena

2014-01-01

Genome integrity is fundamental for cell survival and cell cycle progression. Important mechanisms for keeping the genome intact are proper sister chromatid segregation, correct gene regulation and efficient repair of damaged DNA. Cohesin and its DNA loader, the Scc2/4 complex have been implicated in all these cellular actions. The gene regulation role has been described in several organisms. In yeast it has been suggested that the proteins in the cohesin network would effect transcription based on its role as insulator. More recently, data are emerging indicating direct roles for gene regulation also in yeast. Here we extend these studies by investigating whether the cohesin loader Scc2 is involved in regulation of gene expression. We performed global gene expression profiling in the absence and presence of DNA damage, in wild type and Scc2 deficient G2/M arrested cells, when it is known that Scc2 is important for DNA double strand break repair and formation of damage induced cohesion. We found that not only the DNA damage specific transcriptional response is distorted after inactivation of Scc2 but also the overall transcription profile. Interestingly, these alterations did not correlate with changes in cohesin binding. PMID:25483075

Dual Paraneoplastic Syndromes: Small Cell Lung Carcinoma-related Oncogenic Osteomalacia, and Syndrome of Inappropriate Antidiuretic Hormone Secretion: Report of a Case and Review of the Literature

PubMed Central

Ng, Roland CK

2011-01-01

Acquired isolated renal phosphate wasting associated with a tumor, known as oncogenic osteomalacia or tumor-induced osteomalacia, is a rare paraneoplastic syndrome caused by overproduction of fibroblast growth factor 23. Oncogenic osteomalacia is usually associated with benign mesenchymal tumors. Syndrome of inappropriate antidiuretic hormone secretion (SIADH), on the other hand, is a common paraneoplastic syndrome caused by small cell carcinoma (SCC). Concomitant oncogenic osteomalacia and SIADH associated with SCC is very rare with only 4 other cases reported in the literature. The authors report a case of small cell lung cancer (SCLC)-related renal wasting hypophosphatemia and concurrent SIADH, and review the literature reporting 9 other cases of SCC associated with oncogenic osteomalacia. Almost half of reported cases of renal phosphate wasting associated with SCC concomitantly presented with SIADH. These cases had initial serum phosphorus level lower and survival periods shorter than those without SIADH. This rare combination of a dual paraneoplastic syndrome and low serum phosphorus may be a poor prognostic sign. In addition, both renal phosphate wasting and SIADH usually occur in a short period of time before identification of SCC. Therefore, renal wasting hypophosphatemia with concomitant SIADH/hyponatremia should prompt a search for SCC rather than a benign mesenchymal tumor. PMID:21886301

Dual paraneoplastic syndromes: small cell lung carcinoma-related oncogenic osteomalacia, and syndrome of inappropriate antidiuretic hormone secretion: report of a case and review of the literature.

PubMed

Tantisattamo, Ekamol; Ng, Roland C K

2011-07-01

Acquired isolated renal phosphate wasting associated with a tumor, known as oncogenic osteomalacia or tumor-induced osteomalacia, is a rare paraneoplastic syndrome caused by overproduction of fibroblast growth factor 23. Oncogenic osteomalacia is usually associated with benign mesenchymal tumors. Syndrome of inappropriate antidiuretic hormone secretion (SIADH), on the other hand, is a common paraneoplastic syndrome caused by small cell carcinoma (SCC). Concomitant oncogenic osteomalacia and SIADH associated with SCC is very rare with only 4 other cases reported in the literature. The authors report a case of small cell lung cancer (SCLC)-related renal wasting hypophosphatemia and concurrent SIADH, and review the literature reporting 9 other cases of SCC associated with oncogenic osteomalacia. Almost half of reported cases of renal phosphate wasting associated with SCC concomitantly presented with SIADH. These cases had initial serum phosphorus level lower and survival periods shorter than those without SIADH. This rare combination of a dual paraneoplastic syndrome and low serum phosphorus may be a poor prognostic sign. In addition, both renal phosphate wasting and SIADH usually occur in a short period of time before identification of SCC. Therefore, renal wasting hypophosphatemia with concomitant SIADH/hyponatremia should prompt a search for SCC rather than a benign mesenchymal tumor.

Testing lung cancer drugs and therapies in mice

Cancer.gov

National Cancer Institute (NCI) investigators have designed a genetically engineered mouse for use in the study of human lung squamous cell carcinoma (SCC). SCC is a type of non-small cell lung carcinoma, one of the most common types of lung cancer, with

Clinicopahological features of superficial basaloid squamous cell carcinoma of the esophagus.

PubMed

Oguma, J; Ozawa, S; Kazuno, A; Nitta, M; Ninomiya, Y; Tomita, S

2017-12-01

Basaloid squamous cell carcinoma (BSC) of the esophagus is classified as an epithelial malignant tumor and is a rare variant of squamous cell carcinoma (SCC). Most previous reports have suggested that advanced BSC has a poorer prognosis than typical SCC because of its high biological malignancy, but the biological activity of superficial BSC remains unclear. Twenty cases of superficial BSC, which underwent surgical resection in Tokai University Hospital between January 2004 and December 2013, were analyzed retrospectively. Among these cases, 19 cases with a T1 depth of invasion (BSC group) were compared with 180 cases of SCC that were resected during the same period and were pathologically diagnosed as T1 (SCC group). The frequency of lymph node metastasis in the T1 BSC group was significantly lower (2 patients, 11%) than that in the SCC group (84 patients, 47%) (P = 0.005). The frequency of lymphatic invasion in the BSC group was also lower (9 patients, 47%) than that in the SCC group (131 patients, 73%) (P = 0.021). The pathological type of the metastatic lymph node was BSC in all the superficial BSC cases with lymph node metastasis. This study demonstrated that lymph node metastasis was less likely to occur in cases with superficial BSC than in cases with superficial SCC. © The Authors 2017. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Integration of high-risk human papillomavirus into cellular cancer-related genes in head and neck cancer cell lines.

PubMed

Walline, Heather M; Goudsmit, Christine M; McHugh, Jonathan B; Tang, Alice L; Owen, John H; Teh, Bin T; McKean, Erin; Glover, Thomas W; Graham, Martin P; Prince, Mark E; Chepeha, Douglas B; Chinn, Steven B; Ferris, Robert L; Gollin, Susanne M; Hoffmann, Thomas K; Bier, Henning; Brakenhoff, Ruud; Bradford, Carol R; Carey, Thomas E

2017-05-01

Human papillomavirus (HPV)-positive oropharyngeal cancer is generally associated with excellent response to therapy, but some HPV-positive tumors progress despite aggressive therapy. The purpose of this study was to evaluate viral oncogene expression and viral integration sites in HPV16- and HPV18-positive squamous cell carcinoma lines. E6/E7 alternate transcripts were assessed by reverse transcriptase-polymerase chain reaction (RT-PCR). Detection of integrated papillomavirus sequences (DIPS-PCR) and sequencing identified viral insertion sites and affected host genes. Cellular gene expression was assessed across viral integration sites. All HPV-positive cell lines expressed alternate HPVE6/E7 splicing indicative of active viral oncogenesis. HPV integration occurred within cancer-related genes TP63, DCC, JAK1, TERT, ATR, ETV6, PGR, PTPRN2, and TMEM237 in 8 head and neck squamous cell carcinoma (HNSCC) lines but UM-SCC-105 and UM-GCC-1 had only intergenic integration. HPV integration into cancer-related genes occurred in 7 of 9 HPV-positive cell lines and of these 6 were from tumors that progressed. HPV integration into cancer-related genes may be a secondary carcinogenic driver in HPV-driven tumors. © 2017 Wiley Periodicals, Inc. Head Neck 39: 840-852, 2017. © 2017 Wiley Periodicals, Inc.

The notch pathway is activated in neoplastic progression in esophageal squamous cell carcinoma.

PubMed

Lubin, Daniel J; Mick, Rosemarie; Shroff, Stuti G; Stashek, Kristen; Furth, Emma E

2018-02-01

The Notch signaling pathway is integral to normal human development and homeostasis and has a deterministic function on cell differentiation. Recent studies suggest aberrant Notch signaling may contribute to neoplastic progression by an increase in stem cell survival, chemoresistance, and the promotion of epithelial-to-mesenchymal transition. The goals of our study were to determine, utilizing quantitative technologies, the expression of activated Notch 1 in esophageal squamous cell carcinoma (SCC) and to determine the relationship between Notch 1 expression and various clinicopathologic parameters. Immunohistochemical staining for Notch intracellular domain (NICD) was performed on 60 consecutive cases of esophageal squamous cell carcinoma, 42 cases of benign esophageal squamous epithelium, and 13 cases of eosinophilic esophagitis diagnosed in our department from 2007 through 2015, and exact nuclear staining and nuclear characteristics were graded using the Vectra imaging system. Clinicopathologic data (gender, age at diagnosis, smoking status, tumor grade, tumor stage, tumor location, and survival) were collected for each SCC case and these were correlated with NICD staining. Cases of esophageal SCC demonstrated significantly higher NICD staining compared to cases of benign and reactive esophageal epithelium (P=.003 and .005, respectively). Among cases of esophageal SCC, nuclear NICD staining was significantly correlated with both tumor grade and stage. Following classification and regression tree analysis, esophageal SCC patients with increased NICD expression were found to be more likely to die from their disease than those with lower levels of expression. Taken together, the findings suggest that increased Notch 1 may contribute to the development and aggressiveness of esophageal SCC. Copyright © 2017 Elsevier Inc. All rights reserved.

Identification of Key Transcription Factors Associated with Lung Squamous Cell Carcinoma

PubMed Central

Zhang, Feng; Chen, Xia; Wei, Ke; Liu, Daoming; Xu, Xiaodong; Zhang, Xing; Shi, Hong

2017-01-01

Background Lung squamous cell carcinoma (lung SCC) is a common type of lung cancer, but its mechanism of pathogenesis is unclear. The aim of this study was to identify key transcription factors in lung SCC and elucidate its mechanism. Material/Methods Six published microarray datasets of lung SCC were downloaded from Gene Expression Omnibus (GEO) for integrated bioinformatics analysis. Significance analysis of microarrays was used to identify differentially expressed genes (DEGs) between lung SCC and normal controls. The biological functions and signaling pathways of DEGs were mapped in the Gene Otology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database, respectively. A transcription factor gene regulatory network was used to obtain insights into the functions of DEGs. Results A total of 1,011 genes, including 539 upregulated genes and 462 downregulated genes, were filtered as DEGs between lung SCC and normal controls. DEGs were significantly enriched in cell cycle, DNA replication, p53 signaling pathway, pathways in cancer, adherens junction, and cell adhesion molecules signaling pathways. There were 57 transcription factors identified, which were used to construct a regulatory network. The network consisted of 736 interactions between 49 transcription factors and 486 DEGs. NFIC, BRCA1, and NFATC2 were the top 3 transcription factors that had the highest connectivity with DEGs and that regulated 83, 82, and 75 DEGs in the network, respectively. Conclusions NFIC, BRCA1, and NFATC2 might be the key transcription factors in the development of lung SCC by regulating the genes involved in cell cycle and DNA replication pathways. PMID:28081052

C-Jun expression in lichen planus, psoriasis, and cutaneous squamous cell carcinoma, an immunohistochemical study.

PubMed

Abdou, Asmaa Gaber; Marae, Alaa Hassan; Shoeib, Mohammed; Dawood, Ghada; Abouelfath, Enas

2018-01-01

The AP-1 transcription factor complex is a key player in regulating inflammatory processes, cell proliferation, differentiation, and cell transformation. The aim of the present study is to investigate C-Jun (one of AP-1complex) expression and its proliferative role in skin samples of lichen planus, psoriasis as common inflammatory skin diseases and squamous cell carcinoma using immunohistochemical method. The present study was carried out on skin biopsies of 15 psoriatic patients, 15 lichen planus patients, 15 SCC, and 15 normal skin biopsies. Nuclear expression of C-Jun was detected in basal and few suprabasal layers of epidermis of normal skin. C-Jun was expressed in the whole epidermal layers of both psoriasis (14/15) and lichen planus (15/15) in addition to its expression in lymphocytic infiltrate in the latter in about half of cases (8/15). C-Jun was also expressed in 93.3% (14/15) of SCC in a percentage lower than that of psoriasis, lichen planus, and normal skin. The percentage of C-Jun expression in SCC was significantly associated with an early stage (p = 0.000), free surgical margins (p = 0.022), and small tumour size (p = 0.003). The marked reduction of C-Jun in SCC in comparison to normal skin and inflammatory skin dermatoses may refer to its tumour suppressor activity. C-Jun expression in SCC carries favourable prognosis. Absence of significant association between C-Jun and Ki-67 either in SCC or inflammatory skin diseases indicates that it does not affect proliferative capacity of cells.

Effect of mastitis treatment and somatic cell counts on milk yield in Danish organic dairy cows.

PubMed

Bennedsgaard, T W; Enevoldsen, C; Thamsborg, S M; Vaarst, M

2003-10-01

Production and disease data from 17,488 lactations in 48 Danish organic dairy herds from 1997 to 2001 were analyzed to obtain estimates on the effect of somatic cell counts (SCC) and mastitis treatment on milk production. A multilevel three-parameter piecewise random coefficients linear model with energy-corrected milk (ECM) as dependent variable and herd, lactation, and test days as levels, was used to model the lactation curve. Covariates related to production, SCC, veterinary treatments, and reproductive performance in the previous lactation as well as information on other diseases in the current lactation were included to describe the production capacity of the individual cow. The average daily milk production at herd level was 20.8, 24.2, and 25.8 kg of ECM/d in first, second, and third or later lactation. The estimates for production losses were on average 0.2, 0.3, and 0.4 kg of ECM/d in first, second, and third or later lactation with each twofold increase in SCC between 100,000 and 1,500,000 cells/ml. The effect varied with the stage of lactation and was nonsignificant around 60 d postpartum and highest at the end of the lactation. The production losses in cows treated for mastitis varied with parity and stage of lactation and were modified by the SCC after treatment. For a cow in third lactation with a SCC below 100,000 cells/ ml before treatment at days in milk = 15, the predicted loss was 435 kg of ECM, including a loss of 135 kg of ECM because of higher SCC compared with the level before treatment. Most of the variation in production related to SCC and mastitis was at the lactation level, and no significant differences were found between herds grouped according to milk production level, SCC, or prevalence of mastitis treatment.

Citrus consumption and risk of basal cell carcinoma and squamous cell carcinoma of the skin.

PubMed

Wu, Shaowei; Cho, Eunyoung; Feskanich, Diane; Li, Wen-Qing; Sun, Qi; Han, Jiali; Qureshi, Abrar A

2015-10-01

Animal experiments have demonstrated the photocarcinogenic properties of furocoumarins, a group of naturally occurring chemicals that are rich in citrus products. We conducted a prospective study for citrus consumption and risk of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) of the skin based on data from 41530 men in the Health Professionals Follow-up Study (1986-2010) and 63759 women in the Nurses' Health Study (1984-2010) who were free of cancers at baseline. Over 24-26 years of follow-up, we documented 20840 incident BCCs and 3544 incident SCCs. Compared to those who consumed citrus products less than twice per week, the pooled multivariable-adjusted hazard ratios were 1.03 [95% confidence interval (95% CI): 0.99-1.08] for BCC and 1.14 (95% CI: 1.00-1.30) for SCC for those who consumed two to four times per week, 1.06 (95% CI: 1.01-1.11) for BCC and 1.15 (95% CI: 1.02-1.28) for SCC for five to six times per week, 1.11 (95% CI: 1.06-1.16) for BCC and 1.22 (95% CI: 1.08-1.37) for SCC for once to 1.4 times per day and 1.16 (95% CI: 1.09-1.23) for BCC and 1.21 (95% Cl: 1.06-1.38) for SCC for 1.5 times per day or more (P trend = 0.001 for BCC and 0.04 for SCC). In contrast, consumption of non-citrus fruit and juice appeared to be inversely associated with risk of BCC and SCC. Our findings support positive associations between citrus consumption and risk of cutaneous BCC and SCC in two cohorts of men and women, and call for further investigations to better understand the potential photocarcinogenesis associated with dietary intakes. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Citrus consumption and risk of basal cell carcinoma and squamous cell carcinoma of the skin

PubMed Central

Wu, Shaowei; Cho, Eunyoung; Feskanich, Diane; Li, Wen-Qing; Sun, Qi; Han, Jiali; Qureshi, Abrar A.

2015-01-01

Animal experiments have demonstrated the photocarcinogenic properties of furocoumarins, a group of naturally occurring chemicals that are rich in citrus products. We conducted a prospective study for citrus consumption and risk of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) of the skin based on data from 41530 men in the Health Professionals Follow-up Study (1986–2010) and 63759 women in the Nurses’ Health Study (1984–2010) who were free of cancers at baseline. Over 24–26 years of follow-up, we documented 20840 incident BCCs and 3544 incident SCCs. Compared to those who consumed citrus products less than twice per week, the pooled multivariable-adjusted hazard ratios were 1.03 [95% confidence interval (95% CI): 0.99–1.08] for BCC and 1.14 (95% CI: 1.00–1.30) for SCC for those who consumed two to four times per week, 1.06 (95% CI: 1.01–1.11) for BCC and 1.15 (95% CI: 1.02–1.28) for SCC for five to six times per week, 1.11 (95% CI: 1.06–1.16) for BCC and 1.22 (95% CI: 1.08–1.37) for SCC for once to 1.4 times per day and 1.16 (95% CI: 1.09–1.23) for BCC and 1.21 (95% Cl: 1.06–1.38) for SCC for 1.5 times per day or more (P trend = 0.001 for BCC and 0.04 for SCC). In contrast, consumption of non-citrus fruit and juice appeared to be inversely associated with risk of BCC and SCC. Our findings support positive associations between citrus consumption and risk of cutaneous BCC and SCC in two cohorts of men and women, and call for further investigations to better understand the potential photocarcinogenesis associated with dietary intakes. PMID:26224304

STAT3:FOXM1 and MCT1 drive uterine cervix carcinoma fitness to a lactate-rich microenvironment.

PubMed

Silva, Lidia Santos; Goncalves, Luis Gafeira; Silva, Fernanda; Domingues, Germana; Maximo, Valdemar; Ferreira, Joana; Lam, Eric W-F; Dias, Sergio; Felix, Ana; Serpa, Jacinta

2016-04-01

Uterine cervix cancer is the second most common malignancy in women worldwide with human papillomavirus (HPV) as the etiologic factor. The two main histological variants, squamous cell carcinomas (SCC) and adenocarcinomas (AC), resemble the cell morphology of exocervix and endocervix, respectively. Cancer metabolism is a cancer hallmark conditioned by the microenvironment. As uterine cervix homeostasis is dependent on lactate, we hypothesized lactate plays a role in uterine cervix cancer progression. Using in vitro (SiHa-SCC and HeLa-AC) and BALB-c/SCID models, we demonstrated that lactate metabolism is linked to histological types, with SCC predominantly consuming and AC producing lactate. MCT1 is a key factor, allowing lactate consumption and being regulated in vitro by lactate through the FOXM1:STAT3 pathway. In vivo models showed that SCC (SiHa) expresses MCT1 and is dependent on lactate to grow, whereas AC (HeLa) expresses MCT1 and MCT4, with higher growth capacities. Immunohistochemical analysis of tissue microarrays (TMA) from human cervical tumors showed that MCT1 expression associates with the SCC type and metastatic behavior of AC, whereas MCT4 expression concomitantly increases from in situ SCC to invasive SCC and is significantly associated with the AC type. Consistently, FOXM1 expression is statistically associated with MCT1 positivity in SCC, whereas the expression of FOXO3a, a FOXM1 functional antagonist, is linked to MCT1 negativity in AC. Our study reinforces the role of the microenvironment in the metabolic adaptation of cancer cells, showing that cells that retain metabolic features of their normal counterparts are positively selected by the organ's microenvironment and will survive. In particular, MCT1 was shown to be a key element in uterine cervix cancer development; however, further studies are needed to validate MCT1 as a suitable therapeutic target in uterine cervix cancer.

Immunohistochemical demonstration of EphA2 processing by MT1-MMP in invasive cutaneous squamous cell carcinoma.

PubMed

Tatsukawa, Ryoko; Koga, Kaori; Aoki, Mikiko; Koshikawa, Naohiko; Imafuku, Shinichi; Nakayama, Juichiro; Nabeshima, Kazuki

2016-07-01

Erythropoietin-producing hepatocellular receptor-2 (EphA2) overexpression is prevalent in many types of human cancers, and it has been reported that high EphA2 expression is correlated with malignancy. Recent studies revealed that processing of EphA2 by cleaving off the N-terminal portion by membrane-type 1 matrix metalloproteinase (MT1-MMP) promotes invasion via stimulation of Ras in cancer cells in vitro. The objectives of this study were to investigate the presence and role of EphA2 processing in cutaneous squamous cell carcinoma (SCC) tissues. EphA2 (C-terminal and N-terminal) and MT1-MMP expression patterns and levels were analyzed immunohistochemically in SCC (n = 70) and Bowen disease (BD; n = 20). Levels of MT1-MMP and EphA2 expression were evaluated using digital image analysis. Proximity between MT1-MMP and EphA2 in cancer cells and its effect on EphA2 processing were investigated using a combination of in situ proximity ligation assay (PLA) and Western blotting. Immunohistochemical analyses showed that levels of EphA2 N-terminal expression were significantly lower than those of EphA2 C-terminal expression in SCC, whereas levels of EphA2 C- and N-terminal expression were similar in BD. Western blotting showed processed EphA2 fragments in human SCC tissues. Expression levels of MT1-MMP, EphA2, and processed EphA2 fragments were higher in SCC than BD. Proximity between MT1-MMP and EphA2 in SCC was demonstrated by in situ PLA. Our results suggest possible involvement of MT1-MMP processing of EphA2 in invasiveness of cutaneous SCC.

Contribution of Beta-HPV Infection and UV-Damage to Rapid-onset Cutaneous Squamous Cell Carcinoma during BRAF-inhibition Therapy

PubMed Central

Cohen, Daniel N.; Lawson, Steven K.; Shaver, Aaron C.; Du, Liping; Nguyen, Harrison P.; He, Qin; Johnson, Douglas B.; Lumbang, Wilfred A.; Moody, Brent R.; Prescott, James L.; Chandra, Pranil K.; Boyd, Alan S.; Zwerner, Jeffrey P.; Robbins, Jason B.; Tyring, Stephen K.; Rady, Peter L.; Chappell, James D.; Shyr, Yu; Infante, Jeffrey R.; Sosman, Jeffrey A.

2015-01-01

Purpose BRAF-inhibition (BRAFi) therapy for advanced melanoma carries a high rate of secondary cutaneous squamous cell carcinoma (cSCC) and risk of other cancers. Ultraviolet (UV) radiation and α-genus human papillomavirus (HPV) are highly associated with SCC, but a novel role for β-genus HPV is suspected in BRAFi-cSCC. Cutaneous β-HPV may act in concert with host and environmental factors in BRAFi-cSCC. Experimental Design Primary BRAFi-cSCC tissue DNA isolated from patients receiving vemurafenib (Vem) or dabrafenib from two cancer centers was analyzed for the presence of cutaneous oncogenic viruses and host genetic mutations. Diagnostic specimens underwent consensus dermatopathology review. Clinical parameters for UV exposure and disease course were statistically analyzed in conjunction with histopathology. Results Twenty-nine patients contributed 69 BRAFi-cSCC lesions. BRAFi-cSCC had wart-like features (BRAFi-cSCC-WF) in 22% of specimens. During Vem therapy, BRAFi-cSCC-WF arose 11.6 weeks more rapidly than conventional-cSCC when controlled for gender and UV-exposure (p-value=0.03). Among all BRAFi-cSCC, β-genus HPV-17, HPV-38, HPV-111 were most frequently isolated and novel β-HPV genotypes were discovered (CTR, CRT-11, CRT-22). Sequencing revealed 63% of evaluated BRAFi-cSCCs harbored RAS mutations with PIK3CA, CKIT, ALK and EGFR mutations also detected. Conclusions We examined clinical, histopathologic, viral and genetic parameters in BRAFi-cSCC demonstrating rapid onset; wart-like histomorphology; β-HPV-17, HPV-38, and HPV-111 infection; UV damage; and novel ALK and CKIT mutations. Discovered β-HPV genotypes expand the spectrum of tumor-associated viruses. These findings enhance our understanding of factors cooperating with BRAF inhibition that accelerate keratinocyte oncogenesis as well as broaden the knowledge base of multifactorial mediators of cancer in general. PMID:25724524

Patterns and timing of sunlight exposure and risk of basal cell and squamous cell carcinomas of the skin--a case-control study.

PubMed

Iannacone, Michelle R; Wang, Wei; Stockwell, Heather G; O'Rourke, Kathleen; Giuliano, Anna R; Sondak, Vernon K; Messina, Jane L; Roetzheim, Richard G; Cherpelis, Basil S; Fenske, Neil A; Rollison, Dana E

2012-09-20

Non-melanoma skin cancer (NMSC), comprised of basal (BCC) and squamous (SCC) cell carcinomas, is the most common cancer in Caucasians. Ultraviolet radiation (UVR) exposure is the most important environmental risk factor for NMSC. However, the precise relationship between UVR and the risk of NMSC is complex, and the relationship may differ by skin cancer type. A case-control study was conducted among Florida residents to investigate measures of patterns (intermittent vs. continuous) and timing (childhood vs. adulthood) of sunlight exposure in BCC and SCC. Participants included 218 BCC and 169 SCC cases recruited from a university dermatology clinic and 316 controls with no history of skin or other cancers. A history of blistering sunburn (a measure of intermittent sunlight exposure) was associated with both BCC (OR = 1.96, 95% CI = 1.27-3.03) and SCC (OR = 2.02, 95% CI = 1.22-3.33). Additionally, having a job in the sun for ≥ 3 months for 10 years or longer (a measure of continuous sunlight exposure) was also associated with both BCC and SCC in our study population. With the exception of younger age at first blistering sunburn, measures of younger age at sunlight exposure tended to be associated with SCC, but not BCC risk. Results from the current study suggest that sunlight exposure is associated with both BCC and SCC risk regardless of the pattern in which the exposure was received (i.e. intermittent vs. continuous). The data also suggest that sunlight exposure at a younger age may be more important for SCC but not BCC, however additional studies are needed to further characterize sunlight exposure-response relationships in different types of NMSC.

Patterns and timing of sunlight exposure and risk of basal cell and squamous cell carcinomas of the skin – a case–control study

PubMed Central

2012-01-01

Background Non-melanoma skin cancer (NMSC), comprised of basal (BCC) and squamous (SCC) cell carcinomas, is the most common cancer in Caucasians. Ultraviolet radiation (UVR) exposure is the most important environmental risk factor for NMSC. However, the precise relationship between UVR and the risk of NMSC is complex, and the relationship may differ by skin cancer type. Methods A case–control study was conducted among Florida residents to investigate measures of patterns (intermittent vs. continuous) and timing (childhood vs. adulthood) of sunlight exposure in BCC and SCC. Participants included 218 BCC and 169 SCC cases recruited from a university dermatology clinic and 316 controls with no history of skin or other cancers. Results A history of blistering sunburn (a measure of intermittent sunlight exposure) was associated with both BCC (OR = 1.96, 95% CI = 1.27-3.03) and SCC (OR = 2.02, 95% CI = 1.22-3.33). Additionally, having a job in the sun for ≥3 months for 10 years or longer (a measure of continuous sunlight exposure) was also associated with both BCC and SCC in our study population. With the exception of younger age at first blistering sunburn, measures of younger age at sunlight exposure tended to be associated with SCC, but not BCC risk. Conclusions Results from the current study suggest that sunlight exposure is associated with both BCC and SCC risk regardless of the pattern in which the exposure was received (i.e. intermittent vs. continuous). The data also suggest that sunlight exposure at a younger age may be more important for SCC but not BCC, however additional studies are needed to further characterize sunlight exposure-response relationships in different types of NMSC. PMID:22994655

Protease-Activated Receptor-2 Is Associated with Terminal Differentiation of Epidermis and Eccrine Sweat Glands

PubMed Central

Shin, Yong-Sup; Kim, Hyung Won; Kim, Chang Deok; Kim, Hyun-Woo; Park, Jin Woon; Jung, Sunggyun; Lee, Jeung-Hoon; Ko, Young-Kwon

2015-01-01

Background Protease-activated receptor 2 (PAR-2) participates in various biological activities, including the regulation of epidermal barrier homeostasis, inflammation, pain perception, and melanosome transfer in the skin. Objective To evaluate the basic physiological role of PAR-2 in skin. Methods We investigated PAR-2 expression in human epidermis, skin tumors, and cultured epidermal cells using western blot and immunohistochemical analysis. Additionally, we examined the effect of the PAR-2 agonist, SLIGRL-NH2, on cultured keratinocytes. Results Strong PAR-2 immunoreactivity was observed in the granular layer of normal human skin and the acrosyringium of the eccrine sweat glands. In contrast, weak PAR-2 immunoreactivity was seen in the granular layer of callused skin and in the duct and gland cells of the eccrine sweat glands. Interestingly, PAR-2 immunoreactivity was very weak or absent in the tumor cells of squamous cell carcinoma (SCC) and syringoma. PAR-2 was detected in primary keratinocytes and SV-40T-transformed human epidermal keratinocytes (SV-HEKs), an immortalized keratinocyte cell line, but not in SCC12 cells. SV-HEKs that were fully differentiated following calcium treatment displayed higher PAR-2 expression than undifferentiated SV-HEKs. Treatment of cultured SV-HEKs with PAR-2 agonist increased loricrin and filaggrin expression, a terminal differentiation marker. Conclusion Our data suggest that PAR-2 is associated with terminal differentiation of epidermis and eccrine sweat glands. PMID:26273149

Protease-Activated Receptor-2 Is Associated with Terminal Differentiation of Epidermis and Eccrine Sweat Glands.

PubMed

Shin, Yong-Sup; Kim, Hyung Won; Kim, Chang Deok; Kim, Hyun-Woo; Park, Jin Woon; Jung, Sunggyun; Lee, Jeung-Hoon; Ko, Young-Kwon; Lee, Young Ho

2015-08-01

Protease-activated receptor 2 (PAR-2) participates in various biological activities, including the regulation of epidermal barrier homeostasis, inflammation, pain perception, and melanosome transfer in the skin. To evaluate the basic physiological role of PAR-2 in skin. We investigated PAR-2 expression in human epidermis, skin tumors, and cultured epidermal cells using western blot and immunohistochemical analysis. Additionally, we examined the effect of the PAR-2 agonist, SLIGRL-NH2, on cultured keratinocytes. Strong PAR-2 immunoreactivity was observed in the granular layer of normal human skin and the acrosyringium of the eccrine sweat glands. In contrast, weak PAR-2 immunoreactivity was seen in the granular layer of callused skin and in the duct and gland cells of the eccrine sweat glands. Interestingly, PAR-2 immunoreactivity was very weak or absent in the tumor cells of squamous cell carcinoma (SCC) and syringoma. PAR-2 was detected in primary keratinocytes and SV-40T-transformed human epidermal keratinocytes (SV-HEKs), an immortalized keratinocyte cell line, but not in SCC12 cells. SV-HEKs that were fully differentiated following calcium treatment displayed higher PAR-2 expression than undifferentiated SV-HEKs. Treatment of cultured SV-HEKs with PAR-2 agonist increased loricrin and filaggrin expression, a terminal differentiation marker. Our data suggest that PAR-2 is associated with terminal differentiation of epidermis and eccrine sweat glands.

Cutaneous Squamous Cell Carcinoma With Sclerosing Features: An Uncommon and Potentially Aggressive Variant.

PubMed

Ronen, Shira; Gru, Alejandro A; Noland, Mary M; Rowe, David M; Wick, Mark R

2018-05-08

Sclerosing squamous cell carcinoma (SCC), also known as "desmoplastic" SCC, is a rare subtype of cutaneous malignancy. This variant is clinically significant because it is associated with an increased risk of local recurrence and metastasis. We herein present 16 examples of sclerotic SCC of the skin in 8 men and 3 women, with a median age of 66 years. The most common site of origin for this tumor is the skin of the head and neck, including the scalp (5 tumors in 2 different patients), forehead (3 cases), nasal ala (2 cases), neck (2 cases in the same patient), ear (2 cases), cheek (1 case), and chest (1 case). Microscopically, sclerosing SCCs are characterized by cellular cords, nests, and islands, as well as scattered single cells infiltrating densely desmoplastic and collagenized connective tissue. The differential diagnosis principally includes sclerosing basal cell carcinoma, microcystic adnexal carcinoma, and desmoplastic trichoepithelioma. The main goals of this study are to further characterize these lesions pathologically, and increase general awareness of this SCC subtype.

Impact of subclinical mastitis on greenhouse gas emissions intensity and profitability of dairy cows in Norway.

PubMed

Özkan Gülzari, Şeyda; Vosough Ahmadi, Bouda; Stott, Alistair W

2018-02-01

Impaired animal health causes both productivity and profitability losses on dairy farms, resulting in inefficient use of inputs and increase in greenhouse gas (GHG) emissions produced per unit of product (i.e. emissions intensity). Here, we used subclinical mastitis as an exemplar to benchmark alternative scenarios against an economic optimum and adjusted herd structure to estimate the GHG emissions intensity associated with varying levels of disease. Five levels of somatic cell count (SCC) classes were considered namely 50,000 (i.e. SCC50), 200,000, 400,000, 600,000 and 800,000cells/mL (milliliter) of milk. The effects of varying levels of SCC on milk yield reduction and consequential milk price penalties were used in a dynamic programming (DP) model that maximizes the profit per cow, represented as expected net present value, by choosing optimal animal replacement rates. The GHG emissions intensities associated with different levels of SCC were then computed using a farm-scale model (HolosNor). The total culling rates of both primiparous (PP) and multiparous (MP) cows for the five levels of SCC scenarios estimated by the model varied from a minimum of 30.9% to a maximum of 43.7%. The expected profit was the highest for cows with SCC200 due to declining margin over feed, which influenced the DP model to cull and replace more animals and generate higher profit under this scenario compared to SCC50. The GHG emission intensities for the PP and MP cows with SCC50 were 1.01kg (kilogram) and 0.95kg carbon dioxide equivalents (CO 2 e) per kg fat and protein corrected milk (FPCM), respectively, with the lowest emissions being achieved in SCC50. Our results show that there is a potential to reduce the farm GHG emissions intensity by 3.7% if the milk production was improved through reducing the level of SCC to 50,000cells/mL in relation to SCC level 800,000cells/mL. It was concluded that preventing and/or controlling subclinical mastitis consequently reduces the GHG emissions per unit of product on farm that results in improved profits for the farmers through reductions in milk losses, optimum culling rate and reduced feed and other variable costs. We suggest that further studies exploring the impact of a combination of diseases on emissions intensity are warranted. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Effect of parathyroid hormone on transport by toad and turtle bladder

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sabatini, S.; Kurtzman, N.A.

1987-01-01

The authors recently demonstrated that parathyroid hormone (PTH) inhibited both vasopressin- and cyclic AMP-stimulated water transport in the toad bladder. This was associated with an increase in calcium uptake by isolated epithelial cells. They postulated that PTH exerts its action on H/sub 2/O transport by directly stimulating calcium uptake. The current study was designed to compare the effects of PTH and the calcium ionophore, A23187, on H/sub 2/O and Na transport and H..mu.. secretion in toad and turtle bladders. In toad bladder, PTH and A23187 decreased arginine vasopressin (AVP)-stimulated H/sub 2/O flow and short-circuit current (SCC) after 60 min serosalmore » incubation. In turtle bladder A23187 decreased SCC to 79.3 +/- 3.6% of base line (P < 0.05), and significantly decreased RSCC as well. PTH had no effect on SCC or H/sup +/ secretion in turtle bladders. Both PTH and A23187 increased /sup 45/Ca uptake in toad bladder epithelial cells; only A23187 increased /sup 45/Ca uptake in the turtle bladder. The different action of PTH in these two membranes, compared with that of the calcium ionophore, illustrates the selectivity of PTH on membrane transport. PTH increases calcium uptake and decreases transport only in a hormone-sensitive epithelium, whereas the ionophore works in virtually all living membranes. The mode of action of these two agents to increase calcium uptake is, therefore likely different.« less

Influence of raw milk quality on fluid milk shelf life.

PubMed

Barbano, D M; Ma, Y; Santos, M V

2006-03-01

Pasteurized fluid milk shelf life is influenced by raw milk quality. The microbial count and somatic cell count (SCC) determine the load of heat-resistant enzymes in milk. Generally, high levels of psychrotrophic bacteria in raw milk are required to contribute sufficient quantities of heat-stable proteases and lipases to cause breakdown of protein and fat after pasteurization. Sanitation, refrigeration, and the addition of CO2 to milk are used to control both total and psychrotrophic bacteria count. It is not uncommon for total bacterial counts of raw milk to be < 10,000 cfu/mL. In the past, fluid milk processors have not focused much attention on milk SCC. Increased SCC is correlated with increased amounts of heat-stable protease (plasmin) and lipase (lipoprotein lipase) in milk. When starting with raw milk that has a low bacterial count, and in the absence of microbial growth in pasteurized milk, enzymes associated with high SCC will cause protein and fat degradation during refrigerated storage, and produce off-flavors. As the ability to kill, remove, or control microbial growth in pasteurized refrigerated milk continues to improve, the original milk SCC will be the factor limiting the time of refrigerated storage before development of an off-flavor in milk. Most healthy cows in a dairy herd have a milk SCC < 50,000 cell/mL. Bulk tank SCC > 200,000 cell/mL are usually due to the contribution of high SCC milk from a small number of cows in the herd. Technology to identify these cows and keep their milk out of the bulk tank could substantially increase the value of the remaining milk for use in fluid milk processing. To achieve a 60- to 90-d shelf life of refrigerated fluid milk, fluid processors and dairy farmers need to work together to structure economic incentives that allow farmers to produce milk with the SCC needed for extended refrigerated shelf life.

Incidence, demographics and surgical outcomes of cutaneous squamous cell carcinoma diagnosed in Northland, New Zealand.

PubMed

Elliott, Brodie M; Douglass, Benjamin R; McConnell, Daniel; Johnson, Blair; Harmston, Christopher

2018-05-18

Non-melanoma skin cancer (NMSC) is the most commonly diagnosed and most costly cancer in Australasia. Cutaneous squamous cell carcinoma (cSCC) accounts for approximately 25% of NMSC. Despite this, reporting of cSCC is not mandatory in Australasia. This creates difficulties in planning, resourcing and improving outcomes in cSCC. Previous studies in New Zealand have lacked data on ethnicity. The aim of this study was to define the incidence and demographics of cSCC diagnosed in Northland, New Zealand, including data on ethnicity. A 12-month retrospective study was carried out of all primary cSCC histologically diagnosed in Northland for one year. The cohort was identified by searching the Northland District Health Board pathology database. Data on outcomes and ethnicity were obtained from the hospital results system. Primary outcome of interest was the incidence of cSCC in Northland. Secondary outcomes of interest were lesion characteristics and positive margin rate. 1,040 cSCC were identified in 890 patients. Mean age of patients was 75. Crude incidence of primary cSCC was 668/100,000 patient years. Age standardised incidence was 305/100,000 patient years. An estimate of New Zealand incidence adjusted for age and ethnicity is 580/100,000 patient years. Overall positive margin rate in excised lesions was 9.5%. This study has defined the rate of cSCC in a large, well defined New Zealand population, and estimated age and ethnicity adjusted incidence in New Zealand. It has demonstrated the highest incidence of cSCC in the world outside Australia. Overall positive margin rate of excised lesions was acceptable.

Consequence for dairy herds in the United States of imposing different standards for somatic cell count

USDA-ARS?s Scientific Manuscript database

New European Union (E.U.) regulations may require that a somatic cell count (SCC) limit of 400,000 cells/mL for milk be met by every farm that contributes to pooled milk exported to Europe. In the United States, the standard is 750,000 cells/mL. Because bulk tank SCC is not readily available through...

Microbiological quality and somatic cell count in bulk milk of dromedary camels (Camelus dromedarius): descriptive statistics, correlations, and factors of variation.

PubMed

Nagy, P; Faye, B; Marko, O; Thomas, S; Wernery, U; Juhasz, J

2013-09-01

The objectives of the present study were to monitor the microbiological quality and somatic cell count (SCC) of bulk tank milk at the world's first large-scale camel dairy farm for a 2-yr period, to compare the results of 2 methods for the enumeration of SCC, to evaluate correlation among milk quality indicators, and to determine the effect of specific factors (year, season, stage of lactation, and level of production) on milk quality indicators. The study was conducted from January 2008 to January 2010. Total viable count (TVC), coliform count (CC), California Mastitis Test (CMT) score, and SCC were determined from daily bulk milk samples. Somatic cell count was measured by using a direct microscopic method and with an automatic cell counter. In addition, production parameters [total daily milk production (TDM, kg), number of milking camels (NMC), average milk per camel (AMC, kg)] and stage of lactation (average postpartum days, PPD) were recorded for each test day. A strong correlation (r=0.33) was found between the 2 methods for SCC enumeration; however, values derived using the microscopic method were higher. The geometric means of SCC and TVC were 394×10(3) cells/mL and 5,157 cfu/mL during the observation period, respectively. Somatic cell count was >500×10(3) cells/mL on 14.6% (106/725) and TVC was >10×10(3) cfu/mL on 4.0% (30/742) of the test days. Both milk quality indicators had a distinct seasonal pattern. For log SCC, the mean was lowest in summer and highest in autumn. The seasonal pattern of log TVC was slightly different, with the lowest values being recorded during the spring. The monthly mean TVC pattern showed a clear difference between years. Coliform count was <10 cfu/mL in most of the samples (709/742, 95.6%). A positive correlation was found between log SCC and log TVC (r=0.32), between log SCC and CMT score (r=0.26), and between log TVC and CC in yr 1 (r=0.30). All production parameters and stage of lactation showed strong seasonal variation. Log SCC was negatively correlated with TDM (r=-0.35), AMC (r=-0.37), and NMC (r=-0.15) and positively correlated with PPD (r=0.40). Log TVC had a negative correlation with AMC (r=-0.40) but a positive correlation with NMC (r=0.32), TDM (r=0.16), and PPD (r=0.45). The linear mixed model with stepwise variable selection showed that the main sources of log SCC variation were PPD, TDM, PPD × season, and season. For log TVC, the same factors and year contributed to the variation. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Differentiating oral lesions in different carcinogenesis stages with optical coherence tomography

NASA Astrophysics Data System (ADS)

Tsai, Meng-Tsan; Lee, Cheng-Kuang; Lee, Hsiang-Chieh; Chen, Hsin-Ming; Chiang, Chun-Pin; Wang, Yih-Ming; Yang, Chih-Chung

2009-07-01

A swept-source optical coherence tomography (SS-OCT) system is used to clinically scan oral lesions in different oral carcinogenesis stages, including normal oral mucosa control, mild dysplasia (MiD), moderate dysplasia (MoD), early-stage squamous cell carcinoma (ES-SCC), and well-developed SCC (WD-SCC), for diagnosis purpose. On the basis of the analyses of the SS-OCT images, the stages of dysplasia (MiD and MoD), and SCC (ES-SCC and WD-SCC) can be differentiated from normal control by evaluating the depth-dependent standard deviation (SD) values of lateral variations. In the dysplasia stage, the boundary between the epithelium (EP) and lamina propria (LP) layers can still be identified and the EP layer becomes significantly thicker than that of normal control. Also, in a certain range of the EP layer above the EP/LP boundary, the SD value becomes larger than a certain percentage of the maximum level, which is observed around the EP/LP boundary. On the other hand, in the ES-SCC and WD-SCC stages, the EP/LP boundary disappears. Because of the higher density of connective tissue papillae in the ES-SCC stage, the SD values of the slowly varying lateral scan profiles in the ES-SCC samples are significantly larger than those in the WD-SCC sample. Also, ES-SCC can be differentiated from WD-SCC by comparing the exponential decay constants of averaged A-mode scan profiles. Because of the higher tissue absorption in the WD-SCC lesion, the decay constants in the WD-SCC samples are significantly higher than those in the ES-SCC samples.

Tyrosine Kinase Inhibition in HPV-related Squamous Cell Carcinoma Reveals Beneficial Expression of cKIT and Src.

PubMed

Kramer, Benedikt; Kneissle, Marcel; Birk, Richard; Rotter, Nicole; Aderhold, Christoph

2018-05-01

Therapeutic options of locally advanced or metastatic head and neck squamous cell carcinoma (HNSCC) are limited. Src and cKIT are key protein regulators for local tumor progression. The aim of the study was to investigate the therapeutic potential of targeted therapies in human squamous cell carcinoma (HNSCC) in vitro. Therefore, the influence of the selective tyrosine kinase inhibitors niotinib, dasatinib, erlotinib, gefitinib and afatinib on Src and cKIT expression in Human papilloma virus (HPV)-positive and HPV-negative squamous cancer cells (SCC) was analyzed in vitro. ELISA was performed to evaluate the expression of Src and cKIT under the influence of nilotinib, dasatinib, erlotinib, gefitinib and afatinib (10 μmol/l) in HPV-negative and HPV-positive SCC (24-96 h of incubation). Gefitinib significantly increased cKIT expression in HPV-positive and HPV-negative cells whereas nilotinib and afatinib decreased cKIT expression in HPV-positive SCC. The influence of tyrosine kinase inhibitors in HPV-negative SCC was marginal. Surprisingly, Src expression was significantly increased by all tested tyrosine kinase inhibitors in HPV-positive SCC. The results revealed beneficial and unexpected information concerning the interaction of selective tyrosine kinase inhibitors and the tumor biology of HNSCC. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Bronchial airway gene expression signatures in mouse lung squamous cell carcinoma and their modulation by cancer chemopreventive agents

PubMed Central

Szabo, Eva; Miller, Mark Steven; Lubet, Ronald A.; You, Ming; Wang, Yian

2017-01-01

Due to exposure to environmental toxicants, a “field cancerization” effect occurs in the lung resulting in the development of a field of initiated but morphologically normal appearing cells in the damaged epithelium of bronchial airways with dysregulated gene expression patterns. Using a mouse model of lung squamous cell carcinoma (SCC), we performed transcriptome sequencing (RNA-Seq) to profile bronchial airway gene expression and found activation of the PI3K and Myc signaling networks in cytologically normal bronchial airway epithelial cells of mice with preneopastic lung SCC lesions, which was reversed by treatment with the PI3K Inhibitor XL-147 and pioglitazone, respectively. Activated MYC signaling was also present in premalignant and tumor tissues from human lung SCC patients. In addition, we identified a key microRNA, mmu-miR-449c-5p, whose suppression significantly up-regulated Myc expression in the normal bronchial airway epithelial cells of mice with early stage SCC lesions. We developed a novel bronchial genomic classifier in mice and validated it in humans. In the classifier, Ppbp (pro-platelet basic protein) was overexpressed 115 fold in the bronchial airways of mice with preneoplastic lung SCC lesions. This is the first report that demonstrates Ppbp as a novel biomarker in the bronchial airway for lung cancer diagnosis. PMID:27935865

A case of squamous cell carcinoma presenting as localized severe periodontitis in the maxillary gingiva.

PubMed

Kim, Ok-Su; Uhm, So-Won; Kim, Sang-Chul; Lee, Bo-Ah; Kim, Ok-Joon; Kim, Young-Joon; Chung, Hyun-Ju

2012-06-01

Squamous cell carcinoma (SCC) is the most common malignant neoplasm of the oral cavity. The clinical features of gingival SCC include alveolar bone loss and erythematous lesion. Therefore, gingival SCC sometimes presents as advanced periodontitis. This case report describes a patient diagnosed with gingival SCC after the extraction of molars presenting as being affected by localized severe periodontitis. The patient was a 61-year-old man whose chief complaint was pain in the left maxillary area. Clinical and radiographic examinations revealed common findings of a periodontal abscess on the left maxillary first and second molars. These teeth were extracted based on a diagnosis of a periodontal abscess. Three months later, a rapidly growing exophytic soft tissue mass was observed, and a biopsy of the mass was performed. According to the biopsy, the final diagnosis was a well-differentiated SCC. The patient was treated with a partial maxillectomy of the left maxilla and split-thickness skin graft. Two years after treatment, the patient remained free of recurrence. Gingival SCC is quite different from other forms of SCC, mimicking localized periodontal disease. Therefore, it can be misdiagnosed as localized periodontal disease and is generally discovered after extracting teeth. Therefore, clinicians must diagnose these lesions carefully and follow up with the patient after tooth extraction.

Assessment of salivary total antioxidant capacity in patients with primary untreated head and neck squamous cell carcinoma with ORAC.

PubMed

Wesołowski, Piotr; Zawada, Katarzyna; Wojtowicz, Andrzej; Strużycka, Izabela; Kamiński, Tomasz

2016-11-01

Oxidative DNA damage leads to abnormalities in endogenous cellular processes and constitutes a direct link between free radicals, antioxidants and squamous cell carcinoma (SCC). Oxygen radical absorbance capacity (ORAC) method is used to measure antioxidant capacity versus oxygen free radicals. There is no report on the application of ORAC to evaluate salivary antioxidant capacity in patients with head and neck SCC. This study investigated the relation between total antioxidant capacity of saliva, measured with ORAC method, and the incidence, location, size and histopathological grading of SCC. Salivary antioxidant capacity was assessed in 30 male and female patients with histopathologically confirmed oral and laryngeal SCC. Histopathological grading of SCC was based on WHO classification. Mean ORAC in patients with SCC was higher than the mean value in the control group. Statistically significant difference was observed in the study group versus the control group. No significant differences were observed for ORAC values in relation to histopathological grading, tumour size and spread to lymph nodes. The obtained results can advocate local compensatory mechanism in saliva in response to increased oxidative stress associated with primary tumour. ORAC can become an additional factor in head and neck SCC prognosis, but further investigation is required. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Photodynamic therapy and tumor imaging of hypericin-treated squamous cell carcinoma

PubMed Central

Head, Christian S; Luu, Quang; Sercarz, Joel; Saxton, Romaine

2006-01-01

Background Conventional cancer therapy including surgery, radiation, and chemotherapy often are physically debilitating and largely ineffective in previously treated patients with recurrent head and neck squamous cell carcinoma (SCC). A natural photochemical, hypericin, could be a less invasive method for laser photodynamic therapy (PDT) of these recurrent head and neck malignancies. Hypericin has powerful photo-oxidizing ability, tumor localization properties, and fluorescent imaging capabilities as well as minimal dark toxicity. The current study defined hypericin PDT in vitro with human SCC cells before the cells were grown as tumor transplants in nude mice and tested as a model for hypericin induced tumor fluorescence and PDT via laser fiberoptics. Methods SNU squamous carcinoma cells were grown in tissue culture, detached from monolayers with trypsin, and incubated with 0.1 μg to 10 μg/ml of hypericin before exposure to laser light at 514, 550, or 593 nm to define optimal dose, time, and wavelength for PDT of tumor cells. The SCC cells also were injected subcutaneously in nude mice and grown for 6–8 weeks to form tumors before hypericin injection and insertion of fiberoptics from a KTP532 surgical laser to assess the feasibility of this operating room instrument in stimulating fluorescence and PDT of tumors. Results In vitro testing revealed a hypericin dose of 0.2–0.5 μg/ml was needed for PDT of the SCC cells with an optimal tumoricidal response seen at the 593 nm light absorption maximum. In vivo tumor retention of injected hypericin was seen for 7 to10 days using KTP532 laser induced fluorescence and biweekly PDT via laser fiberoptics led to regression of SCC tumor transplants under 0.4 cm2 diameter, but resulted in progression of larger size tumors in the nude mice. Conclusion In this preclinical study, hypericin was tested for 514–593 nm dye laser PDT of human SCC cells in vitro and for KTP532 surgical laser targeting of SCC tumors in mice. The results suggest hypericin is a potent tumor imaging agent using this surgical laser that may prove useful in defining tumor margins and possibly in sterilizing post-resection margins. Deeply penetrating pulsed infrared laser emissions will be needed for PDT of larger and more inaccessible tumors. PMID:17147827

A graphic system for telemetry monitoring and procedure performing at the Telecom SCC

NASA Technical Reports Server (NTRS)

Loubeyre, Jean Philippe

1994-01-01

The increasing amount of telemetry parameters and the increasing complexity of procedures used for the in-orbit satellite follow-up has led to the development of new tools for telemetry monitoring and procedures performing. The name of the system presented here is Graphic Server. It provides an advanced graphic representation of the satellite subsystems, including real-time telemetry and alarm displaying, and a powerful help for decision making with on line contingency procedures. Used for 2.5 years at the TELECOM S.C.C. for procedure performing, it has become an essential part of the S.C.C.

Cutaway line drawing of STS-34 middeck experiment Polymer Morphology (PM)

NASA Technical Reports Server (NTRS)

1989-01-01

Cutaway line drawing shows components of STS-34 middeck experiment Polymer Morphology (PM). Components include the EAC, heat exchanger, sample cell control (SCC), sample cells, source, interferometer, electronics, carousel drive, infrared (IR) beam, and carousel. PM, a 3M-developed organic materials processing experiment, is designed to explore the effects of microgravity on polymeric materials as they are processed in space. The samples of polymeric materials being studied in the PM experiment are thin films (25 microns or less) approximately 25mm in diameter. The samples are mounted between two infrared transparent windows in a specially designed infrared cell that provides the capability of thermally processing the samples to 200 degrees Celsius with a high degree of thermal control. The samples are mounted on a carousel that allows them to be positioned, one at a time, in the infrared beam where spectra may be acquired. The Generic Electronics Module (GEM) provides all carousel and

Nucleolin overexpression in breast cancer cell sub-populations with different stem-like phenotype enables targeted intracellular delivery of synergistic drug combination.

PubMed

Fonseca, Nuno A; Rodrigues, Ana S; Rodrigues-Santos, Paulo; Alves, Vera; Gregório, Ana C; Valério-Fernandes, Ângela; Gomes-da-Silva, Lígia C; Rosa, Manuel Santos; Moura, Vera; Ramalho-Santos, João; Simões, Sérgio; Moreira, João Nuno

2015-11-01

Breast cancer stem cells (CSC) are thought responsible for tumor growth and relapse, metastization and active evasion to standard chemotherapy. The recognition that CSC may originate from non-stem cancer cells (non-SCC) through plastic epithelial-to-mesenchymal transition turned these into relevant cell targets. Of crucial importance for successful therapeutic intervention is the identification of surface receptors overexpressed in both CSC and non-SCC. Cell surface nucleolin has been described as overexpressed in cancer cells as well as a tumor angiogenic marker. Herein we have addressed the questions on whether nucleolin was a common receptor among breast CSC and non-SCC and whether it could be exploited for targeting purposes. Liposomes functionalized with the nucleolin-binding F3 peptide, targeted simultaneously, nucleolin-overexpressing putative breast CSC and non-SCC, which was paralleled by OCT4 and NANOG mRNA levels in cells from triple negative breast cancer (TNBC) origin. In murine embryonic stem cells, both nucleolin mRNA levels and F3 peptide-targeted liposomes cellular association were dependent on the stemness status. An in vivo tumorigenic assay suggested that surface nucleolin overexpression per se, could be associated with the identification of highly tumorigenic TNBC cells. This proposed link between nucleolin expression and the stem-like phenotype in TNBC, enabled 100% cell death mediated by F3 peptide-targeted synergistic drug combination, suggesting the potential to abrogate the plasticity and adaptability associated with CSC and non-SCC. Ultimately, nucleolin-specific therapeutic tools capable of simultaneous debulk multiple cellular compartments of the tumor microenvironment may pave the way towards a specific treatment for TNBC patient care. Copyright © 2015 Elsevier Ltd. All rights reserved.

A Novel Model for Squamous Cell Carcinoma of the Lung | Center for Cancer Research

Cancer.gov

In the U.S. lung cancer remains the most deadly cancer type with less than one in five patients alive five years after diagnosis. The majority of lung cancer deaths are due to tobacco smoke, and the squamous cell carcinoma (SCC) subtype of lung cancer is strongly associated with smoking. Researchers have identified a number of mutations in lung SCC tumors but have failed to generate an animal model of lung SCC, which is critical for understanding the biology of the disease and for identifying novel therapeutic targets.

SOLITARY CHEMORECEPTOR CELL SURVIVAL IS INDEPENDENT OF INTACT TRIGEMINAL INNERVATION

PubMed Central

Gulbransen, Brian; Silver, Wayne; Finger, Tom

2008-01-01

Nasal solitary chemoreceptor cells (SCCs) are a population of specialized chemosensory epithelial cells presumed to broaden trigeminal chemoreceptivity in mammals (Finger et al., 2003). SCCs are innervated by peptidergic trigeminal nerve fibers (Finger et al., 2003) but it is currently unknown if intact innervation is necessary for SCC development or survival. We tested the dependence of SCCs on innervation by eliminating trigeminal nerve fibers during development with neurogenin-1 knockout mice, during early postnatal development with capsaicin desensitization, and during adulthood with trigeminal lesioning. Our results demonstrate that elimination of innervation at any of these times does not result in decreased SCC numbers. In conclusion, neither SCC development nor mature cell maintenance is dependent on intact trigeminal innervation. PMID:18300260

Differential repair of radiation-induced DNA damage in cells of human squamous cell carcinoma and the effect of caffeine and cysteamine on induction and repair of DNA double-strand breaks

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smeets, M.F.M.A.; Mooren, E.H.M.; Abdel-Wahab, A.H.A.

1994-11-01

The goal of these experiments was to investigate further the relationship between DNA double-strand breaks and cell killing in human tumor cells, first by comparing different cell lines, and second by radiomodification studies. Field-inversion gel electrophoresis was used to quantify double-strand breaks. Two subclones of the radioresistant human squamous cell carcinoma line SQ20B (SQD9 and SQG6) were compared. These subclones differed in DNA index by a factor of 1.7 but showed the same resistance to radiation as cells of the parental cell line. It was found that, although induction of DSBs was not significantly different in the two cell lines,more » the t{sub 1/2} of the fast component of repair was significantly shorter for SQD9 cells, leading to greater overall repair which was not reflected in increased survival. Caffeine and cysteamine were tested as modifiers of radiosensitivity, using the radioresistant SQ20B line and the radiosensitive SCC61 cell line. No effect of caffeine was seen when the drug was present only during irradiation. Postirradiation incubations with caffeine, however, resulted in a dose reduction factor greater than 2.0 in cell survival for both cell lines. In contrast, induction of DSBs was reduced by caffeine, and no effect on DSB repair was observed. Cysteamine led to a dose protection factor greater than 1.8 in cell survival in both cell lines. A reduction in induced DSBs was found at high doses corresponding approximately with the increase in cell survival. Over the same (low) dose range, however, the correlation between DSB induction and cell killing was poor. These data indicate that DSB induction does not correlate well with cell killing either for different cell lines, for radiochemical modification (cysteamine) or for some other types of modification (caffeine). 31 refs., 8 figs.« less

Differential prooxidative effects of the green tea polyphenol, (-)-epigallocatechin-3-gallate, in normal and oral cancer cells are related to differences in sirtuin 3 signaling.

PubMed

Tao, Ling; Park, Jong-Yung; Lambert, Joshua D

2015-02-01

We have previously reported that the green tea catechin, (-)-epigallocatechin-3-gallate (EGCG), can induce oxidative stress in oral cancer cells but exerts antioxidant effects in normal cells. Here, we report that these differential prooxidative effects are associated with sirtuin 3 (SIRT3), an important mitochondrial redox modulator. EGCG rapidly induced mitochondria-localized reactive oxygen species in human oral squamous carcinoma cells (SCC-25, SCC-9) and premalignant leukoplakia cells (MSK-Leuk1), but not in normal human gingival fibroblast cells (HGF-1). EGCG suppressed SIRT3 mRNA and protein expression, as well as, SIRT3 activity in SCC-25 cells, whereas it increased SIRT3 activity in HGF-1 cells. EGCG selectively decreased the nuclear localization of the estrogen-related receptor α (ERRα), the transcription factor regulating SIRT3 expression, in SCC-25 cells. This indicates that EGCG may regulate SIRT3 transcription in oral cancer cells via ERRα. EGCG also differentially modulated the mRNA expressions of SIRT3-associated downstream targets including glutathione peroxidase 1 and superoxide dismutase 2 in normal and oral cancer cells. SIRT3 represents a novel potential target through which EGCG exerts differential prooxidant effects in cancer and normal cells. Our results provide new biomarkers to be further explored in animal studies. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Resveratrol suppresses TPA-induced matrix metalloproteinase-9 expression through the inhibition of MAPK pathways in oral cancer cells.

PubMed

Lin, Feng-Yan; Hsieh, Yi-Hsien; Yang, Shun-Fa; Chen, Chang-Tai; Tang, Chih-Hsin; Chou, Ming-Yung; Chuang, Yi-Ting; Lin, Chiao-Wen; Chen, Mu-Kuan

2015-10-01

Naturally occurring agents, such as resveratrol, have been determined to benefit health. Numerous studies have demonstrated that resveratrol has antioxidative, cardioprotective, and neuroprotective properties. However, the effect of resveratrol exerts on the metastasis of oral cancer cells remains unclear. In this study, we investigated the effect the anti-invasive activity of resveratrol on a human oral cancer cell line (SCC-9) in vitro and the underlying mechanisms. Cell viability was examined by MTT assay, whereas cell motility was measured by migration and wound-healing assays. Zymography, reverse-transcriptase polymerase chain reaction (PCR), and promoter assays confirmed the inhibitory effects of resveratrol on matrix metalloproteinase-9 (MMP-9) expression in oral cancer cells. We established that various concentrations (0-100 μM) of resveratrol inhibited the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced migration capacities of SCC-9 cells and caused no cytotoxic effects. Zymography and Western blot analyses suggested that resveratrol inhibited TPA-induced MMP-9 gelatinolytic activity and protein expression. In addition, the results indicated that resveratrol inhibited the phosphorylation of c-Jun N-terminal kinase (JNK)1/2 and extracellular-signal-regulated kinase (ERK)1/2 involved in downregulating protein expression and the transcription of MMP-9. In summary, resveratrol inhibited MMP-9 expression and oral cancer cell metastasis by downregulating JNK1/2 and ERK1/2 signals pathways and, thus, exerts beneficial effects in chemoprevention. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Risk of head and neck squamous cell cancer and death in patients with Fanconi anemia who did and did not receive transplants.

PubMed

Rosenberg, Philip S; Socié, Gerard; Alter, Blanche P; Gluckman, Eliane

2005-01-01

Hematopoietic stem cell transplant (SCT) is currently the only therapy that can restore normal hematopoiesis in patients with Fanconi anemia (FA). Patients with FA have a high baseline risk of squamous cell cancers (SCCs) of the head, neck, and esophagus, and SCT conditioning may increase SCC incidence. We evaluated the risks of SCC and death in 145 patients with FA in the North American Survey (NAS) cohort who did not receive transplants, and 117 patients with FA in the Hôpital Saint Louis (SLH) cohort who did receive transplants. The age-specific hazard of SCC was 4.4-fold higher in patients who received transplants than in those who did not (P = .003), and SCCs occurred at significantly younger ages in the former (respective medians, 18 and 33 years, P = .004). Survival after SCC was similarly poor in both cohorts (P = .135, median, 13 months). The hazard of SCC increased at a greater than linear rate, to 4.4% per year by age 40 in NAS and 4.7% per year by 10 years after transplant in SLH. In SLH, the hazard of non-SCC death was biphasic, declining significantly (P = .004) from 7.1% per month during the first 6 months after transplant to 0.13% per month (1.6% per year) after the first year. Acute and chronic graft-versus-host diseases were significant SCC risk factors. Adverse event rates in these cohorts provide historical control rates to assess emerging therapies for FA.

Clinicopathological roles of S100A8 and S100A9 in cutaneous squamous cell carcinoma in vivo and in vitro.

PubMed

Choi, Dae-Kyoung; Li, Zheng Jun; Chang, In-Kyu; Yeo, Min-Kyung; Kim, Jin-Man; Sohn, Kyung-Cheol; Im, Myung; Seo, Young-Joon; Lee, Jeung-Hoon; Kim, Chang-Deok; Lee, Young

2014-07-01

S100A8 and S100A9 are members of the S100 protein family and exist in neutrophils, monocytes, and macrophages. Recent studies have shown that S100A8 and S100A9 are associated with various neoplastic disorders; however, their roles in cutaneous squamous cell carcinoma (SCC) are not well defined. To investigate the expression and function of S100A8 and S100A9 in skin tumors, we examined the expression levels of S100A8 and S100A9 between premalignant and malignant skin tumors and investigated the functional roles of S100A8 and S100A9 in vitro and in vivo using recombinant adenovirus expressing S100A8 or S100A9. The immunopositive staining rates and intensities of S100A8 and S100A9 were higher in SCC than in premalignant skin tumors. When S100A8 and/or S100A9 were overexpressed in SCC12 cells using a recombinant adenovirus, cell growth and motility were increased. Similarly, when mouse skin was intradermally injected with SCC12 cells overexpressing S100A8 and/or S100A9, there were remarkable increases in tumor growth and volume. Both S100A8 and S100A9 are highly expressed in cutaneous SCC and play important roles in tumorigenesis. We suggest that S100A8 and S100A9 may be potential therapeutic targets for the prevention or treatment of SCC in skin.

Targeting of the tumor suppressor GRHL3 by a miR-21-dependent proto-oncogenic network results in PTEN loss and tumorigenesis.

PubMed

Darido, Charbel; Georgy, Smitha R; Wilanowski, Tomasz; Dworkin, Sebastian; Auden, Alana; Zhao, Quan; Rank, Gerhard; Srivastava, Seema; Finlay, Moira J; Papenfuss, Anthony T; Pandolfi, Pier Paolo; Pearson, Richard B; Jane, Stephen M

2011-11-15

Despite its prevalence, the molecular basis of squamous cell carcinoma (SCC) remains poorly understood. Here, we identify the developmental transcription factor Grhl3 as a potent tumor suppressor of SCC in mice, and demonstrate that targeting of Grhl3 by a miR-21-dependent proto-oncogenic network underpins SCC in humans. Deletion of Grhl3 in adult epidermis evokes loss of expression of PTEN, a direct GRHL3 target, resulting in aggressive SCC induced by activation of PI3K/AKT/mTOR signaling. Restoration of Pten expression completely abrogates SCC formation. Reduced levels of GRHL3 and PTEN are evident in human skin, and head and neck SCC, associated with increased expression of miR-21, which targets both tumor suppressors. Our data define the GRHL3-PTEN axis as a critical tumor suppressor pathway in SCC. 2011 Elsevier Inc. All rights reserved.

Size of cervical lymph node and metastasis in squamous cell carcinoma of the oral tongue and floor of mouth.

PubMed

Jarungroongruangchai, Weerawut; Charoenpitakchai, Mongkol; Silpeeyodom, Tawatchai; Pruksapong, Chatchai; Burusapat, Chairat

2014-02-01

Squamous cell carcinoma (SCC) of the oral tongue and floor of mouth are the most common head and neck cancers. Regional metastasis of SCC is most likely found at the cervical lymph node. Size and characteristics of pathologically suspicious lymph nodes are related to the aggressiveness of the primary tumor: The objective of this study is to analyze the conrrelation between sizes of cervical node and metastasis in SCC of oral tongue and floor of mouth. Retrospective review was conducted firom the patient's charts between January 2008 and December 2012. Clinical, histopathology and surgical records were reviewed. Cervical lymph nodes ofSCC of oral tongue and floor of mouth were reviewed and divided into four groups depending on their size (1-5 mm, 6-9 mm, 10-30 mm and more than 30 am,). A p-value <0.05 was considered statistically significant. 196 patients with SCC of the oral cavity were recorded. Sixteen patients ofSCC of the oral tongue and 15patients of SCC of the floor of mouth underwent neck dissection (641 cervical nodes). Most ofthe patients were diagnosed with stage 3 (41.94%). Extracapsular extension was found in 72.15% of SCC of oral tongue and 73.33 % of SCC ofthe floor of mouth. Size of cervical lymph nodes less than 10 mm was found to be metastasis at 9.27% and 10.82% of SCC of oral tongue and floor of mouth, respectively. Cervical node metastasis can be found in SCC of the oral tongue and floor ofmouth with clinlically negative node andsize of cervical node less than 10 mm. Here in, size of cervical node less than 10 mm was still important due to the chance for metastasis especially high grade tumors, advanced stage cancer and lymphovascular invasion.

Occupation and relative risk of cutaneous squamous cell carcinoma (cSCC): A 45-year follow-up study in 4 Nordic countries.

PubMed

Alfonso, Jose Hernán; Martinsen, Jan Ivar; Pukkala, Eero; Weiderpass, Elisabete; Tryggvadottir, Laufey; Nordby, Karl-Christian; Kjærheim, Kristina

2016-09-01

The age-adjusted incidence of cutaneous squamous cell carcinoma (cSCC) in the Nordic countries has increased during the last 60 years, and the identification of occupational variation in the relative risk of cSCC may have preventive implications. We sought to describe variation in the relative risk of cSCC between occupational categories in Finland, Iceland, Norway, and Sweden. This is a historical prospective cohort study based on record linkages between census data for 12.9 million people and cancer registry data from 1961 to 2005. Standardized incidence ratios for cSCC were estimated for 53 occupational categories with the cSCC incidence rates for the national population of each country used as reference. During follow-up, 87,619 incident cases of cSCC were reported to the national cancer registries. In all countries combined, significant increased standardized incidence ratios were observed among seamen, military personnel, public safety workers, technical workers, teachers, transport workers, physicians, dentists, nurses, other health workers, religious workers, clerical workers, administrators, and sale agents (standardized incidence ratios between 1.08 and 1.77). Information on occupation was based on 1 point in time only. The occupational variation of the relative risk of cSCC might be associated with socioeconomic factors, and to some extent to occupational exposures. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Detection of Papillomavirus DNA in Cutaneous Squamous Cell Carcinoma and Multiple Papillomas in Captive Reptiles.

PubMed

Eleni, C; Corteggio, A; Altamura, G; Meoli, R; Cocumelli, C; Rossi, G; Friedrich, K G; Di Cerbo, P; Borzacchiello, G

2017-07-01

Papillomaviruses (PVs) are small, non-enveloped DNA viruses that cause mucocutaneous tumours including squamous cell carcinoma (SCC) in man. In animals, evidence supports a causal role for PVs in the development of cutaneous and oral SCC in some species. In reptiles, three cases of papilloma or fibropapilloma have been associated with PV infection, but no association has been reported to date with SCC. Two cases of cutaneous epithelial tumours, multiple papillomas in a spiny-tailed lizard (Uromastyx acanthinura) and SCC in a Dumeril's boa (Acrantophis dumerili), were investigated by polymerase chain reaction. PV DNA was amplified from samples of both lesions. Typical microscopical features suggestive of PV infection (e.g. the presence of koilocytes) were observed in the lesions from the spiny-tailed lizard. This is the first report of an association between PV and SCC in reptiles. Further studies are needed to better clarify the role of PVs in these species and to characterize the PV strains involved. Copyright © 2017 Elsevier Ltd. All rights reserved.

Polymorphism in cytochrome P450 1A2 and their interaction with risk factors in determining risk of squamous cell lung carcinoma in men.

PubMed

Singh, Arvind P; Pant, Mohan C; Ruwali, Munindra; Shah, Parag P; Prasad, Rajendra; Mathur, Neeraj; Parmar, Devendra

The present case-control study was carried out to investigate the association of functionally important polymorphisms of cytochrome P450 1A2 (CYP1A2) involved in the metabolic activation of tobacco derived procarcinogens with squamous cell carcinoma (SCC) of lung in North Indian men. The study consisted of 200 male cases with SCC of lung and an equal number of age and sex matched healthy controls. Our data showed that variant genotype of CYP1A2*1D and CYP1A2*1F were significantly associated with increased susceptibility to SCC of lung. Likewise, GSTM1 null genotype was found to be over represented in patients when compared to controls. Haplotype analysis revealed that haplotype, G-Tdel-T-C was significantly associated with risk to SCC of lung. Moreover, a significant increase in the risk to SCC of lung in the cases carrying combination of variant genotype of CYP1A2 with either CYP1A1 or GSTM1 have shown that gene-gene interactions may play an important role in squamous cell lung cancer risk. Our data also revealed that smokers or tobacco chewers carrying variant alleles of either CYP1A2*1D or CYP1A2*1F were at increased risk to SCC of lung, further demonstrating that CYP1A2 genotypes interact with environmental risk factors in enhancing the risk to squamous cell lung carcinoma.

Inefficient differentiation response to cell cycle stress leads to genomic instability and malignant progression of squamous carcinoma cells

PubMed Central

Alonso-Lecue, Pilar; de Pedro, Isabel; Coulon, Vincent; Molinuevo, Rut; Lorz, Corina; Segrelles, Carmen; Ceballos, Laura; López-Aventín, Daniel; García-Valtuille, Ana; Bernal, José M; Mazorra, Francisco; Pujol, Ramón M; Paramio, Jesús; Ramón Sanz, J; Freije, Ana; Toll, Agustí; Gandarillas, Alberto

2017-01-01

Squamous cell carcinoma (SCC) or epidermoid cancer is a frequent and aggressive malignancy. However in apparent paradox it retains the squamous differentiation phenotype except for very dysplastic lesions. We have shown that cell cycle stress in normal epidermal keratinocytes triggers a squamous differentiation response involving irreversible mitosis block and polyploidisation. Here we show that cutaneous SCC cells conserve a partial squamous DNA damage-induced differentiation response that allows them to overcome the cell division block. The capacity to divide in spite of drug-induced mitotic stress and DNA damage made well-differentiated SCC cells more genomically instable and more malignant in vivo. Consistently, in a series of human biopsies, non-metastatic SCCs displayed a higher degree of chromosomal alterations and higher expression of the S phase regulator Cyclin E and the DNA damage signal γH2AX than the less aggressive, non-squamous, basal cell carcinomas. However, metastatic SCCs lost the γH2AX signal and Cyclin E, or accumulated cytoplasmic Cyclin E. Conversely, inhibition of endogenous Cyclin E in well-differentiated SCC cells interfered with the squamous phenotype. The results suggest a dual role of cell cycle stress-induced differentiation in squamous cancer: the resulting mitotic blocks would impose, when irreversible, a proliferative barrier, when reversible, a source of genomic instability, thus contributing to malignancy. PMID:28661481

Inhibitory effects of marine-derived DNA-binding anti-tumour tetrahydroisoquinolines on the Fanconi anaemia pathway.

PubMed

Martínez, Sandra; Pérez, Laura; Galmarini, Carlos M; Aracil, Miguel; Tercero, Juan C; Gago, Federico; Albella, Beatriz; Bueren, Juan A

2013-10-01

We have previously shown that cells with a defective Fanconi anaemia (FA) pathway are hypersensitive to trabectedin, a DNA-binding anti-cancer tetrahydroisoquinoline (DBAT) whose adducts functionally mimic a DNA inter-strand cross link (ICL). Here we expand these observations to new DBATs and investigate whether our findings in primary untransformed cells can be reproduced in human cancer cells. Initially, the sensitivity of transformed and untransformed cells, deficient or not in one component of the FA pathway, to mitomycin C (MMC) and three DBATs, trabectedin, Zalypsis and PM01183, was assessed. Then, the functional interaction of these drugs with the FA pathway was comparatively investigated. While untransformed FA-deficient haematopoietic cells were hypersensitive to both MMC and DBATs, the response of FA-deficient squamous cell carcinoma (SCC) cells to DBATs was similar to that of their respective FA-competent counterparts, even though these FA-deficient SCC cells were hypersensitive to MMC. Furthermore, while MMC always activated the FA pathway, the DBATs inhibited the FA pathway in the cancer cell lines tested and this enhanced their response to MMC. Our data show that although DBATs functionally interact with DNA as do agents that generate classical ICL, these drugs should be considered as FA pathway inhibitors rather than activators. Moreover, this effect was most significant in a variety of cancer cells. These inhibitory effects of DBATs on the FA pathway could be exploited clinically with the aim of 'fanconizing' cancer cells in order to make them more sensitive to other anti-tumour drugs. © 2013 The British Pharmacological Society.

Inhibitory effects of marine-derived DNA-binding anti-tumour tetrahydroisoquinolines on the Fanconi anaemia pathway

PubMed Central

Martínez, Sandra; Pérez, Laura; Galmarini, Carlos M; Aracil, Miguel; Tercero, Juan C; Gago, Federico; Albella, Beatriz; Bueren, Juan A

2013-01-01

BACKGROUND AND PURPOSE We have previously shown that cells with a defective Fanconi anaemia (FA) pathway are hypersensitive to trabectedin, a DNA-binding anti-cancer tetrahydroisoquinoline (DBAT) whose adducts functionally mimic a DNA inter-strand cross link (ICL). Here we expand these observations to new DBATs and investigate whether our findings in primary untransformed cells can be reproduced in human cancer cells. EXPERIMENTAL APPROACH Initially, the sensitivity of transformed and untransformed cells, deficient or not in one component of the FA pathway, to mitomycin C (MMC) and three DBATs, trabectedin, Zalypsis and PM01183, was assessed. Then, the functional interaction of these drugs with the FA pathway was comparatively investigated. KEY RESULTS While untransformed FA-deficient haematopoietic cells were hypersensitive to both MMC and DBATs, the response of FA-deficient squamous cell carcinoma (SCC) cells to DBATs was similar to that of their respective FA-competent counterparts, even though these FA-deficient SCC cells were hypersensitive to MMC. Furthermore, while MMC always activated the FA pathway, the DBATs inhibited the FA pathway in the cancer cell lines tested and this enhanced their response to MMC. CONCLUSIONS AND IMPLICATIONS Our data show that although DBATs functionally interact with DNA as do agents that generate classical ICL, these drugs should be considered as FA pathway inhibitors rather than activators. Moreover, this effect was most significant in a variety of cancer cells. These inhibitory effects of DBATs on the FA pathway could be exploited clinically with the aim of ‘fanconizing’ cancer cells in order to make them more sensitive to other anti-tumour drugs. PMID:23937566

A Proposed Molecular Mechanism of High-Dose Vitamin D3 Supplementation in Prevention and Treatment of Preeclampsia.

PubMed

Zabul, Piotr; Wozniak, Michal; Slominski, Andrzej T; Preis, Krzysztof; Gorska, Magdalena; Korozan, Marek; Wieruszewski, Jan; Zmijewski, Michal A; Zabul, Ewa; Tuckey, Robert; Kuban-Jankowska, Alicja; Mickiewicz, Wieslawa; Knap, Narcyz

2015-06-09

A randomized prospective clinical study performed on a group of 74 pregnant women (43 presenting with severe preeclampsia) proved that urinary levels of 15-F(2t)-isoprostane were significantly higher in preeclamptic patients relative to the control (3.05 vs. 2.00 ng/mg creatinine). Surprisingly enough, plasma levels of 25-hydroxyvitamin D3 in both study groups were below the clinical reference range with no significant difference between the groups. In vitro study performed on isolated placental mitochondria and placental cell line showed that suicidal self-oxidation of cytochrome P450scc may lead to structural disintegration of heme, potentially contributing to enhancement of oxidative stress phenomena in the course of preeclampsia. As placental cytochrome P450scc pleiotropic activity is implicated in the metabolism of free radical mediated arachidonic acid derivatives as well as multiple Vitamin D3 hydroxylations and progesterone synthesis, we propose that Vitamin D3 might act as a competitive inhibitor of placental cytochrome P450scc preventing the production of lipid peroxides or excess progesterone synthesis, both of which may contribute to the etiopathogenesis of preeclampsia. The proposed molecular mechanism is in accord with the preliminary clinical observations on the surprisingly high efficacy of high-dose Vitamin D3 supplementation in prevention and treatment of preeclampsia.

Do pure squamous cell carcinomas and urothelial carcinomas have similar prognosis after radical cystectomy?

PubMed

Balci, Ugur; Ozer, Kutan; Gorgel, Sacit Nuri; Sefik, Ertugrul; Girgin, Cengiz; Dincel, Cetin

2013-10-01

The purpose of this study was to evaluate the surgical treatment results of urothelial carcinoma (UC) and pure squamous cell carcinoma of the bladder (SCC). The records of 460 patients who have undergone radical cystectomy in our department between the years 1991 and 2011 were analyzed retrospectively, and 364 patients with UC and 60 patients with pure SCC were evaluated. Average ages of the patients with UC and SCC were 61.12 ± 8.9 and 59.38 ± 8.6 years, respectively (p = 0.902). UC group had 29 female patients, whereas SCC group had 9 female patients (p = 0.077). The mean follow-up periods were 26.09 ± 24.75 months for UC group and 22.23 ± 31.01 months for SCC group (p = 0.805). The incidence of organ-confined, extravesical, lymph node-positive diseases in UC and SCC cases was 48.9 and 32.2, 29.3 and 32.2 %, 21.8 and 35.6 %, respectively (p = 0.028). Five-year disease-specific survival (DSS) rates were 57.5 % in UC and 39.1 % in SCC group (p = 0.011). Five-year DSS rates were 81.2 % in UC and 75.0 % in SCC group in organ-confined disease (p = 0.534) and 28.2 % in UC and 40.9 % in SCC group in extravesical disease (p = 0.845). In lymph node-positive patients, DSS time was 20.9 ± 2.85 months in UC and 12.8 ± 2.07 months in SCC patients (p = 0.182). In multivariate analysis, pT stage (HR: 2.221; 95 % CI: 1.695-2.911) and lymph node involvement (HR: 2.863; 95 % CI: 1.819-4.509) were independently associated with DSS (p < 0.001), but histological subtype (HR: 1.423; 95 % CI: 0.798-2.538) was not a statistically significant factor (p = 0.232). Although pure SCC cases are diagnosed at advanced stages of the disease, UC and pure SCC cases have similar prognosis by stages. Lymph node involvement and stages are the most important prognostic factors after radical cystectomy.

Influence of somatic cell count and breed on capillary electrophoretic protein profiles of ewes' milk: a chemometric study.

PubMed

Rodríguez-Nogales, J M; Vivar-Quintana, A M; Revilla, I

2007-07-01

Bulk tank ewe milk from the Assaf, Castellana, and Churra breeds categorized into 3 somatic cell count (SCC) groups (<500,000; 1,000,000 to 1,500,000; and >2,500,000 cells/mL) was used to investigate changes in chemical composition and capillary electrophoresis protein profiles. The results obtained indicated that breed affected fat, protein, and total solids levels, and differences were also observed for the following milk proteins: beta-, beta1-, beta2-, and alpha(s1)-III-casein, alpha-lactalbumin, and beta-lactoglobulin. High SCC affected fat and protein contents and bacterial counts. The level of beta1-, beta2-, and alpha(s1)-I-casein, and alpha-lactalbumin were significantly lower in milk with SCC scores >2,500,000 cells/mL. A preliminary study of the chemical, microbiological, and electrophoretic data was performed by cluster analysis and principal components analysis. Applying discriminant analysis, it was possible to group the milk samples according to breed and level of SCC, obtaining a prediction of 100 and 97% of the samples, respectively.

Is ultraviolet exposure acquired at work the most important risk factor for cutaneous squamous cell carcinoma? Results of the population-based case-control study FB-181.

PubMed

Schmitt, J; Haufe, E; Trautmann, F; Schulze, H-J; Elsner, P; Drexler, H; Bauer, A; Letzel, S; John, S M; Fartasch, M; Brüning, T; Seidler, A; Dugas-Breit, S; Gina, M; Weistenhöfer, W; Bachmann, K; Bruhn, I; Lang, B M; Bonness, S; Allam, J P; Grobe, W; Stange, T; Westerhausen, S; Knuschke, P; Wittlich, M; Diepgen, T L

2018-02-01

Squamous cell carcinoma (SCC) is one of the most frequent types of cancer constituting a significant public health burden. Prevention strategies focus on limiting ultraviolet (UV) exposure during leisure time. However, the relative impact of occupational and nonoccupational UV exposure for SCC occurrence is unclear. To investigate the association between occupational and nonoccupational UV exposure for SCC in a multicentre population-based case-control study hypothesizing that high occupational UV exposure increases the risk of SCC. Consecutive patients with incident SCC (n = 632) were recruited from a German national dermatology network. Population-based controls (n = 996) without history of skin cancer were recruited from corresponding residents' registration offices and propensity score matched to cases. Lifetime UV exposure, sociodemographic and clinical characteristics were assessed by trained physicians. Occupational and nonoccupational UV exposure doses were estimated by masked investigators using established reference values. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were assessed using conditional logistic regression adjusting for relevant confounders. Total solar UV exposure was significantly associated with increased SCC. The OR for high (> 90th percentile) vs. low (< 40th percentile) and high vs, moderate (40-59th percentile) occupational UV exposure was 1·95 (95% CI 1·19-3·18) and 2·44 (95% CI 1·47-4·06) for SCC. Adjusting for occupational UV exposure, nonoccupational UV exposure was not significantly related to SCC incidence. Dose-response relationships were observed for occupational but not for nonoccupational solar UV exposure. Solar occupational UV exposure is a major determinant of incident SCC. Our findings indicate that prevention strategies should be further expanded to the occupational setting. © 2017 British Association of Dermatologists.

Past sexual behaviors and risks of oropharyngeal squamous cell carcinoma: a case-case comparison.

PubMed

Schnelle, Christoph; Whiteman, David C; Porceddu, Sandro V; Panizza, Benedict J; Antonsson, Annika

2017-03-01

The incidence of oropharyngeal squamous cell carcinomas (SCCs) is increasing and is believed to reflect changing sexual practices in recent decades. For this case-case comparative study, we collected medical and life-style information and data on sexual behavior from 478 patients treated at the head and neck clinic of a tertiary hospital in Brisbane, Australia. Patients were grouped as (i) oropharyngeal SCC (n = 96), (ii) oral cavity, larynx and hypopharynx SCC ("other HNSCCs," n = 96), (iii) other SCCs (n = 141), and (iv) other diagnoses (n = 145). We fitted multivariable logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) associated with lifestyle factors and sexual behaviors. Compared to the other three patient groups, the oropharyngeal SCC patients had overall more sexual lifetime partners (kissing, oral sex and sexual intercourse). Oropharyngeal SCC patients were significantly more likely to have ever given oral sex compared to the other three patient groups-93% of oropharyngeal SCC patients, 64% of other HNSCC patients, and 58% of patients with other SCC or other diagnoses. Oropharyngeal SCC patients were significantly more likely to have given oral sex to four or more partners when compared to patients with other HNSCC (odds ratio [OR] 11.9; 95% CI 3.5-40.1), other SCC (OR 16.6; 95% CI 5.3-52.0) or patients with other diagnoses (OR 25.2; 95% CI 7.8-81.7). The very strong associations reported here between oral sex practices and risks of oropharyngeal SCC support the hypothesis that sexually transmitted HPV infections cause some of these cancers. © 2016 UICC.

Actinic keratosis-related signs predictive of squamous cell carcinoma in renal transplant recipients: a nested case-control study.

PubMed

Jiyad, Z; O'Rourke, P; Soyer, H P; Green, A C

2017-04-01

Squamous cell carcinoma (SCC) and intraepidermal carcinoma (IEC) commonly arise in actinically damaged skin. To identify clinical features of actinic change that correlate with an increased risk of SCC or IEC in the short-to-medium term as guidance for prioritizing field treatment. In a nested case-control study, cases were renal transplant recipients who developed an incident SCC or IEC within 18 months following baseline examination and photography. Controls without SCC or IEC were matched to cases on age, sex and duration of immunosuppression. Predefined skin sites on the head, neck and upper limbs were examined using baseline photographs to assess objectively the following features of actinic damage: presence of actinic keratosis (AK) patch (defined as AK > 1 cm 2 ), number of AK patches, number of AKs and area affected by AK. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using McNemar's test to identify differences in SCC/IEC risk combined and SCC risk alone between case and control skin sites. Thirty-nine cases were matched to 39 controls. Significant associations with the presence of an AK patch, number of AK patches, number of AKs and area affected by AKs were identified. The presence of an AK patch conferred an 18-fold increased risk of SCC (OR 18·00, 95% CI 2·84-750) and more than a sixfold increased risk of SCC/IEC combined (OR 6·60, 95% CI 2·56-21·66). AK patches are predictive of SCC/IEC development within 18 months. This can be used to guide site selection for field treatment in patients with widespread actinic damage. © 2016 British Association of Dermatologists.

Keratoacanthoma versus invasive squamous cell carcinoma: a comparison of dermatoscopic vascular features in 510 cases.

PubMed

Pyne, John H; Windrum, Graham; Sapkota, Devendra; Wong, Jian Cheng

2014-07-01

Keratoacanthoma (KA) and invasive squamous cell carcinoma (SCC) are keratinocytic tumors displaying vascular features, imaged using dermatoscopy. Compare the dermatoscopy vascular features of KA to SCC. This prospective study examined consecutive cases of 100 KA and 410 invasive SCC in a single private practice in Sydney, Australia. Vascular features were recorded in vivo direct from patients using a non-polarized Delta 20 Heine dermatoscope. These vascular features were: linear, branching, serpentine, hairpin, glomerular and dot vessels, the presence or absence of large diameter tumor vessels, vessel presence in central verses peripheral tumor areas and tumor pink areas in different proportions. Following full excision, all cases were submitted for histopathologic diagnosis. Branching vessels were the only vessel morphology that varied, with a significant incidence in KA (25.0%), compared to SCC (10.7%), P < 0.01. Large vessels were identified in 20.0% of KA, compared to 12.4% in SCC, P = 0.05. No vessels were observed in the central tumor areas in 43.4 % of KA compared to 58.0% of SCC, P = 0.01. Other data comparing the central versus peripheral tumor areas for vessels present did not reveal any distinctive associations. There were no significant differences between KA and SCC when reviewing the selected proportions of pink within the tumor. The vascular features may be confounded by tumor depth in KA. Polarized dermatoscopy may not produce the same findings. This study found branching vessels to have a higher incidence in KA compared to invasive SCC. Although not statistically significant, large diameter vessels were also more frequent in KA. Proportions of pink within the tumor or central verses peripheral tumor vessel distribution were not useful diagnostic features separating KA from SCC using dermatoscopy.

Case-control study of genus-beta human papillomaviruses in plucked eyebrow hairs and cutaneous squamous cell carcinoma.

PubMed

Iannacone, Michelle R; Gheit, Tarik; Pfister, Herbert; Giuliano, Anna R; Messina, Jane L; Fenske, Neil A; Cherpelis, Basil S; Sondak, Vernon K; Roetzheim, Richard G; Silling, Steffi; Pawlita, Michael; Tommasino, Massimo; Rollison, Dana E

2014-05-01

Cutaneous human papillomaviruses (HPV) have been reported in cutaneous squamous cell carcinoma (SCC). We conducted a clinic-based case-control study to investigate the association between genus-beta HPV DNA in eyebrow hairs (EBH) and SCC. EBH from 168 SCC cases and 290 controls were genotyped for genus-beta HPV DNA. SCC tumors from a subset of cases (n = 142) were also genotyped. Viral load was determined in a subset of specimens positive for a single HPV type. Associations with SCC were estimated by odds ratios (OR) and 95% confidence intervals (CI) adjusted for age and sex using logistic regression. Statistical tests were two-sided. EBH DNA prevalence was greater in cases (87%) than controls (73%) (p < 0.05), and the association with SCC increased with the number of HPV types present, (≥ 4 types vs. HPV-negative: OR = 2.02, 95% CI = 1.07-3.80; p(trend) = 0.02). Type-specific associations were observed between SCC and DNA in EBH for HPV23 (OR = 1.90, 95% CI = 1.10-3.30) and HPV38 (OR = 1.84, 95% CI = 1.04-3.24). Additionally, when compared with the controls, the DNA prevalence in EBH was significantly higher among cases for 11 of the 25 genus-beta types tested, when accounting for DNA for the same HPV type in the tumor (ORs = 3.44-76.50). Compared to controls, the mean viral DNA load in EBH among the selected cases was greater for HPV5, HPV8 and HPV24, but lower for HPV38. SCC cases were more likely than controls to have HPV DNA+ EBH for single and multiple HPV types, providing additional support for the potential role of genus-beta HPV infections in SCC development. © 2013 UICC.

Systemic retinoids for the chemoprevention of cutaneous squamous cell carcinoma and verrucal keratosis in a cohort of patients on BRAF inhibitors.

PubMed

Anforth, R; Blumetti, T C M P; Clements, A; Kefford, R; Long, G V; Fernandez-Peñas, P

2013-12-01

The treatment of metastatic melanoma has changed greatly with the development of inhibitors targeted at the mutated BRAF kinase present in up to 50% of metastatic melanoma cases. These agents, vemurafenib and dabrafenib, have been shown to increase median survival. Unfortunately, they have also been associated with the development of verrucal keratosis (VK) and cutaneous squamous cell carcinoma (cuSCC). These lesions require surgical excision, and when a large number of these lesions need to be treated, it can significantly affect the patient's quality of life. To determine if acitretin is suitable as a chemopreventative agent against the development of verrucal keratosis and cuSCC, in patients on BRAF inhibitors. Patients treated with a BRAF inhibitor, vemurafenib or dabrafenib, for stage IV metastatic melanoma, who had undergone more than five surgical excisions to remove lesions suggestive of cuSCC, were offered the opportunity to commence acitretin as a chemopreventative agent. Patients were evaluated every 4 weeks. Clinical and histological data were collected. Eight patients, who had a total of 24 cuSCC removed, were included in the study. After commencement of acitretin, only five cuSCC were excised from two patients. The most significant reduction was in a patient who had developed 13 cuSCC over 10 months and only two cuSCC 3 months after commencing acitretin. No modifications in the dose of the BRAF inhibitor were made as a result of cuSCC in any of these patients. Acitretin should be considered as a chemopreventative agent for VK and cuSCC in patients taking BRAF inhibitors, before considering dosage reductions. © 2013 British Association of Dermatologists.

ATP7B detoxifies silver in ciliated airway epithelial cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ibricevic, Aida, E-mail: aidaibricevic@hotmail.co; Brody, Steven L., E-mail: sbrody@dom.wustl.ed; Youngs, Wiley J., E-mail: youngs@uakron.ed

2010-03-15

Silver is a centuries-old antibiotic agent currently used to treat infected burns. The sensitivity of a wide range of drug-resistant microorganisms to silver killing suggests that it may be useful for treating refractory lung infections. Toward this goal, we previously developed a methylated caffeine silver acetate compound, SCC1, that exhibits broad-spectrum antimicrobial activity against clinical strains of bacteria in vitro and when nebulized to lungs in mouse infection models. Preclinical testing of high concentrations of SCC1 in primary culture mouse tracheal epithelial cells (mTEC) showed selective ciliated cell death. Ciliated cell death was induced by both silver- and copper-containing compoundsmore » but not by the methylated caffeine portion of SCC1. We hypothesized that copper transporting P-type ATPases, ATP7A and ATP7B, play a role in silver detoxification in the airway. In mTEC, ATP7A was expressed in non-ciliated cells, whereas ATP7B was expressed only in ciliated cells. The exposure of mTEC to SCC1 induced the trafficking of ATP7B, but not ATP7A, suggesting the presence of a cell-specific silver uptake and detoxification mechanisms. Indeed, the expression of the copper uptake protein CTR1 was also restricted to ciliated cells. A role of ATP7B in silver detoxification was further substantiated when treatment of SCC1 significantly increased cell death in ATP7B shRNA-treated HepG2 cells. In addition, mTEC from ATP7B{sup -/-} mice showed enhanced loss of ciliated cells compared to wild type. These studies are the first to demonstrate a cell type-specific expression of the Ag{sup +}/Cu{sup +} transporters ATP7A, ATP7B, and CTR1 in airway epithelial cells and a role for ATP7B in detoxification of these metals in the lung.« less

Relationship between milk cathelicidin abundance and microbiologic culture in clinical mastitis.

PubMed

Addis, M F; Bronzo, V; Puggioni, G M G; Cacciotto, C; Tedde, V; Pagnozzi, D; Locatelli, C; Casula, A; Curone, G; Uzzau, S; Moroni, P

2017-04-01

The availability of reliable tools to enable the sensitive and specific detection of mastitis in dairy cows can assist in developing control strategies and promote the more rational use of antibiotics. We have developed a milk cathelicidin ELISA that shows high sensitivity and specificity for dairy cow mastitis, based on latent class analysis. In this study, we investigated the effect of microbial agents on cathelicidin abundance in the milk of cows with clinical mastitis. We subjected 535 quarter milk samples (435 from quarters showing signs of clinical mastitis and 100 from healthy quarters as a control) to milk cathelicidin ELISA, somatic cell count (SCC), and microbiologic culture. Of the 435 clinical mastitis samples, 431 (99.08%) were positive for cathelicidin, 424 (97.47%) had SCC >200,000 cells/mL, and 376 (86.44%) were culture-positive. Of the 59 culture-negative samples, 58 (98.30%) were positive for cathelicidin and 55 (93.22%) had SCC >200,000 cells/mL. The abundance of cathelicidin and the extent of SCC increase depended on the causative agent: Streptococcus agalactiae and coagulase-negative staphylococci showed the highest and lowest changes, respectively. We also observed differences in behavior between the 2 markers depending on the pathogen: Streptococcus agalactiae induced the highest cathelicidin abundance, and Serratia spp. induced the highest SCC. Nevertheless, the different ability of microorganisms to induce cathelicidin release in milk did not compromise its value as a mastitis marker, given its higher sensitivity compared to SCC or microbiologic culture. All 100 negative control samples (collected from healthy quarters with SCC <100,000 cells/mL and culture-negative) were also negative for cathelicidin, corresponding to 100% specificity in the evaluated sample cohort. This study confirmed the value of the milk cathelicidin ELISA for detecting bovine mastitis, and highlighted the influence of mastitis-causing microorganisms on cathelicidin abundance. This influence did not compromise diagnostic performance; instead, it may have better reflected disease severity and evolution than SCC. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Solitary chemoreceptor cell survival is independent of intact trigeminal innervation.

PubMed

Gulbransen, Brian; Silver, Wayne; Finger, Thomas E

2008-05-01

Nasal solitary chemoreceptor cells (SCCs) are a population of specialized chemosensory epithelial cells presumed to broaden trigeminal chemoreceptivity in mammals (Finger et al. [2003] Proc Natl Acad Sci USA 100:8981-8986). SCCs are innervated by peptidergic trigeminal nerve fibers (Finger et al. [2003]) but it is currently unknown if intact innervation is necessary for SCC development or survival. We tested the dependence of SCCs on innervation by eliminating trigeminal nerve fibers during development with neurogenin-1 knockout mice, during early postnatal development with capsaicin desensitization, and during adulthood with trigeminal lesioning. Our results demonstrate that elimination of innervation at any of these times does not result in decreased SCC numbers. In conclusion, neither SCC development nor mature cell maintenance is dependent on intact trigeminal innervation. (c) 2008 Wiley-Liss, Inc.

Perineural Infiltration of Cutaneous Squamous Cell Carcinoma and Basal Cell Carcinoma Without Clinical Features

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin, Charles, E-mail: Charles_Lin@health.qld.gov.au; Tripcony, Lee; Keller, Jacqui

2012-01-01

Purpose: To review the factors that influence outcome and patterns of relapse in patients with cutaneous squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) with perineural infiltration (PNI) without clinical or radiologic features, treated with surgery and radiotherapy. Methods and Materials: Between 1991 and 2004, 222 patients with SCC or BCC with PNI on pathologic examination but without clinical or radiologic PNI features were identified. Charts were reviewed retrospectively and relevant data collected. All patients were treated with curative intent; all had radiotherapy, and most had surgery. The primary endpoint was 5-year relapse-free survival from the time of diagnosis.more » Results: Patients with SCC did significantly worse than those with BCC (5-year relapse-free survival, 78% vs. 91%; p < 0.01). Squamous cell carcinoma with PNI at recurrence did significantly worse than de novo in terms of 5-year local failure (40% vs. 19%; p < 0.01) and regional relapse (29% vs. 5%; p < 0.01). Depth of invasion was also a significant factor. Of the PNI-specific factors for SCC, focal PNI did significantly better than more-extensive PNI, but involved nerve diameter or presence of PNI at the periphery of the tumor were not significant factors. Conclusions: Radiotherapy in conjunction with surgery offers an acceptable outcome for cutaneous SCC and BCC with PNI. This study suggests that focal PNI is not an adverse feature.« less

MicroRNA-588 suppresses tumor cell migration and invasion by targeting GRN in lung squamous cell carcinoma

PubMed Central

Qian, Li; Lin, Longlong; Du, Yufeng; Hao, Xiaoyan; Zhao, Yuze; Liu, Xuejun

2016-01-01

MicroRNAs (miRNAs) have been demonstrated to be critical in regulating tumor development and progression. The present study investigated the expression of miR-588 using reverse transcription-quantitative polymerase chain reaction analysis in 85 cases of lung squamous cell carcinoma (SCC), and observed the correlation between the expression of miR-588 with clinical pathologic features. The results indicated that the expression of miR-588 was predominantly lower in the tumor samples, compared with non-tumorous samples, and was negatively associated with tumor stages and lymph node invasion. The present study also examined the significance of the expression of miR-588 in SCC using gain- and loss-of-function analyses. It was found that miR-588 inhibited tumor cell migration and invasion. In addition, it was revealed that the overexpression of miR-588 in SCC cells reduced the mRNA and protein levels of progranulin (GRN), whereas miR-588 silencing increased the expression of GRN. A luciferase activity assay showed that miR-588 was able to directly bind to the 3′untranslated region of GRN and regulate its expression. Furthermore, it was found that the expression of GRN was inversely correlated with the expression of miR-588 in 85 paired SCC samples. These results indicated that GRN was involved in the miR-588-mediated suppressive functions in the progression of SCC. PMID:27571908

Squamous cell carcinoma of the scrotum in a radiation technologist and the use of sentinel lymph node biopsy in recurrent disease.

PubMed

Shifrin, David A; Lange, Marianne K; Kahnoski, Richard J; Avallone, Anthony N

2007-03-01

Squamous cell carcinoma (SCC) of the scrotum is an uncommon neoplasm. It has been described in many different occupations and is associated with a myriad of carcinogens, yet the etiology still remains a mystery. This is the first report of its occurrence in a radiation technologist. Additionally, the use of sentinel lymph node biopsy in SCC has been advocated as a safe method of limiting the morbidity associated with bilateral ilioinguinal dissections. This is the first report of its use in recurrent metastatic SCC of the scrotum.

Evaluation of milk cathelicidin for detection of dairy sheep mastitis.

PubMed

Addis, M F; Tedde, V; Dore, S; Pisanu, S; Puggioni, G M G; Roggio, A M; Pagnozzi, D; Lollai, S; Cannas, E A; Uzzau, S

2016-08-01

Mastitis due to intramammary infections is one of the most detrimental diseases in dairy sheep farming, representing a major cause of reduced milk productions and quality losses. In particular, subclinical mastitis presents significant detection and control problems, and the availability of tools enabling its timely, sensitive, and specific detection is therefore crucial. We have previously demonstrated that cathelicidins, small proteins implicated in the innate immune defense of the host, are specifically released in milk of mastitic animals by both epithelial cells and neutrophils. Here, we describe the development of an ELISA for milk cathelicidin and assess its value against somatic cell counts (SCC) and bacteriological culture for detection of ewe mastitis. Evaluation of the cathelicidin ELISA was carried out on 705 half-udder milk samples from 3 sheep flocks enrolled in a project for improvement of mammary health. Cathelicidin was detected in 35.3% of milk samples (249/705), and its amount increased with rising SCC values. The cathelicidin-negative (n=456) and cathelicidin-positive (n=249) sample groups showed a clear separation in relation to SCC, with median values of 149,500 and 3,300,000 cells/mL, respectively. Upon bacteriological culture, 20.6% (145/705) of the milk samples showed microbial growth, with coagulase-negative staphylococci being by far the most frequent finding. A significant proportion of all bacteriologically positive milk samples were positive for cathelicidin (110/145, 75.9%). Given the lack of a reliable gold standard for defining the true disease status, sensitivity (Se) and specificity (Sp) of the cathelicidin ELISA were assessed by latent class analysis against 2 SCC thresholds and against bacteriological culture results. At an SCC threshold of 500,000 cells/mL, Se and Sp were 92.3 and 92.3% for cathelicidin ELISA, 89.0 and 94.9% for SCC, and 39.4 and 93.6% for bacteriological culture, respectively. At an SCC threshold of 1,000,000 cells/mL, Se and Sp were 93.3 and 91.9% for cathelicidin ELISA, 80.0 and 97.1% for SCC, and 39.4 and 93.5% for bacteriology, respectively. In view of the results obtained in this study, the measurement of cathelicidin in milk by ELISA can provide added Se while maintaining a high Sp and may therefore improve detection of subclinical mastitis. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Diagnosis of subclinical mastitis in Santa Inês and Morada Nova sheep in southeastern Brazil.

PubMed

Zafalon, Luiz Francisco; Santana, Raul Costa Mascarenhas; Pilon, Lucas Eduardo; Júnior, Guilherme Aparecido Fim

2016-06-01

The objective of this study was to evaluate different screening limits for the California mastitis test (CMT) and the somatic cell count (SCC) in previous diagnoses of subclinical mastitis in Santa Inês and Morada Nova ewes, which were reared under the same management conditions. Additionally, cutoff points were defined for SCC in accordance with the sensitivity and specificity of the test. A total of 907 mammary halves were subjected to CMT and SCC. The disease was confirmed by means of microbiological identification. Coagulase-negative staphylococci (CNS) were the microorganisms with highest occurrence. The CMT score of 1+ provided adequate sensitivity and specificity at all periods of lactation investigated. This score showed good agreement with SCC, >400,000 cells mL(-1). Higher cell counts favored higher diagnostic specificity. They can be used when producers have financial difficulties relating to treatment or culling of sheep with subclinical mastitis. However, producers should be warned about the risk of false-negative results in the flock.

Semicircular Canals Circumvent Brownian Motion Overload of Mechanoreceptor Hair Cells.

PubMed

Muller, Mees; Heeck, Kier; Elemans, Coen P H

2016-01-01

Vertebrate semicircular canals (SCC) first appeared in the vertebrates (i.e. ancestral fish) over 600 million years ago. In SCC the principal mechanoreceptors are hair cells, which as compared to cochlear hair cells are distinctly longer (70 vs. 7 μm), 10 times more compliant to bending (44 vs. 500 nN/m), and have a 100-fold higher tip displacement threshold (< 10 μm vs. <400 nm). We have developed biomechanical models of vertebrate hair cells where the bundle is approximated as a stiff, cylindrical elastic rod subject to friction and thermal agitation. Our models suggest that the above differences aid SCC hair cells in circumventing the masking effects of Brownian motion noise of about 70 nm, and thereby permit transduction of very low frequency (<10 Hz) signals. We observe that very low frequency mechanoreception requires increased stimulus amplitude, and argue that this is adaptive to circumvent Brownian motion overload at the hair bundles. We suggest that the selective advantage of detecting such low frequency stimuli may have favoured the evolution of large guiding structures such as semicircular canals and otoliths to overcome Brownian Motion noise at the level of the mechanoreceptors of the SCC.

Semicircular Canals Circumvent Brownian Motion Overload of Mechanoreceptor Hair Cells

PubMed Central

Muller, Mees; Heeck, Kier

2016-01-01

Vertebrate semicircular canals (SCC) first appeared in the vertebrates (i.e. ancestral fish) over 600 million years ago. In SCC the principal mechanoreceptors are hair cells, which as compared to cochlear hair cells are distinctly longer (70 vs. 7 μm), 10 times more compliant to bending (44 vs. 500 nN/m), and have a 100-fold higher tip displacement threshold (< 10 μm vs. <400 nm). We have developed biomechanical models of vertebrate hair cells where the bundle is approximated as a stiff, cylindrical elastic rod subject to friction and thermal agitation. Our models suggest that the above differences aid SCC hair cells in circumventing the masking effects of Brownian motion noise of about 70 nm, and thereby permit transduction of very low frequency (<10 Hz) signals. We observe that very low frequency mechanoreception requires increased stimulus amplitude, and argue that this is adaptive to circumvent Brownian motion overload at the hair bundles. We suggest that the selective advantage of detecting such low frequency stimuli may have favoured the evolution of large guiding structures such as semicircular canals and otoliths to overcome Brownian Motion noise at the level of the mechanoreceptors of the SCC. PMID:27448330

Developments in SCC Mitigation by Electrocatalysis

NASA Astrophysics Data System (ADS)

Andresen, Peter L.; Kim, Young J.

SCC is strongly influenced by water chemistry parameters, especially when crack chemistry can be concentrated from differential aeration or thermal gradients or boiling. Mitigation of the effects of the high corrosion potential associated with oxidants is markedly and efficiently accomplished by electrocatalysis, which requires that there be a stoichiometric excess of reductants over oxidants. Mechanisms and criteria for effective SCC mitigation are summarized, with particular focus on the critical location for the catalyst in a crack and experimental support for these concepts. Optimization of electrocatalysis by OnLine NobleChem- is described, for example where Pt is injected at levels of 0.002 to 0.05 ppb in the reactor water.

Microbiota of Cow’s Milk; Distinguishing Healthy, Sub-Clinically and Clinically Diseased Quarters

PubMed Central

Oikonomou, Georgios; Bicalho, Marcela Lucas; Meira, Enoch; Rossi, Rodolfo Elke; Foditsch, Carla; Machado, Vinicius Silva; Teixeira, Andre Gustavo Vieira; Santisteban, Carlos; Schukken, Ynte Hein; Bicalho, Rodrigo Carvalho

2014-01-01

The objective of this study was to use pyrosequencing of the 16S rRNA genes to describe the microbial diversity of bovine milk samples derived from clinically unaffected quarters across a range of somatic cell counts (SCC) values or from clinical mastitis, culture negative quarters. The obtained microbiota profiles were used to distinguish healthy, subclinically and clinically affected quarters. Two dairy farms were used for the collection of milk samples. A total of 177 samples were used. Fifty samples derived from healthy, culture negative quarters with a SCC of less than 20,000 cells/ml (group 1); 34 samples derived from healthy, culture negative quarters, with a SCC ranging from 21,000 to 50,000 cells/ml (group 2); 26 samples derived from healthy, culture negative quarters with a SCC greater than 50,000 cells/ml (group 3); 34 samples derived from healthy, culture positive quarters, with a SCC greater than 400,000 (group 4, subclinical); and 33 samples derived from clinical mastitis, culture negative quarters (group 5, clinical). Bacterial DNA was isolated from these samples and the 16S rRNA genes were individually amplified and pyrosequenced. All samples analyzed revealed great microbial diversity. Four bacterial genera were present in every sample obtained from healthy quarters (Faecalibacterium spp., unclassified Lachnospiraceae, Propionibacterium spp. and Aeribacillus spp.). Discriminant analysis models showed that samples derived from healthy quarters were easily discriminated based on their microbiota profiles from samples derived from clinical mastitis, culture negative quarters; that was also the case for samples obtained from different farms. Staphylococcus spp. and Streptococcus spp. were among the most prevalent genera in all groups while a general multivariable linear model revealed that Sphingobacterium and Streptococcus prevalences were associated with increased 10 log SCC. Conversely, Nocardiodes and Paenibacillus were negatively correlated, and a higher percentage of the genera was associated with a lower 10 log SCC. PMID:24465777

p16 immunostaining in keratinocytic neoplasia in organ transplant recipients: Bowen's disease shows a characteristic pattern.

PubMed

Genders, Roel E; Beck, Samuel; Bouwes Bavinck, Jan Nico; van den Munckhof, Henk A M; Kouwenhoven, Stijn T P; de Koning, Maurits N C; de Gruijl, Frank R; Jenkins, David; Willemze, Rein; Quint, Koen D

2017-01-01

For selecting therapy, it is important to distinguish different types of keratinocytic neoplasia. It is sometimes difficult to make histopathologic diagnosis, especially in organ transplant recipients (OTR) who develop numerous lesions. To investigate p16 immunostaining in different types of keratinocytic neoplasia in OTR, we studied 59 actinic keratoses (AK), 51 Bowen' s disease (BD), 63 squamous cell carcinomas (SCC), 16 benign keratotic lesions (BKL) from 31 OTR patients and 25 controls (eczema and psoriasis). Tissue sections were stained for H&E and p16. We scored intensity, proportion and distribution of p16 positive lesional cells. In 19% of AK, 92% of BD, 35% of SCC and 12% of BKL more than 15% of lesional cells were p16-positive. In 16% of AK, 80% of BD, 18% of SCC and 13% of BKL strong p16 staining was observed. BKL, AK and SCC showed focal and patchy staining, BD showed diffuse pattern with strong staining of all atypical cells. Sparing of the basal layer was predominantly seen in BD. No control specimen showed p16-overexpression. p16 immunostaining shows a characteristic pattern in BD, but not in AK, SCC and BKL. It appears useful in recognizing BD, but not in differentiating between other keratinocytic neoplasia. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

GAB2 Amplification in Squamous Cell Lung Cancer of Non-Smokers

PubMed Central

2017-01-01

Lung squamous cell cancer (SCC) is typically found in smokers and has a very low incidence in non-smokers, indicating differences in the tumor biology of lung SCC in smokers and non-smokers. However, the specific mutations that drive tumor growth in non-smokers have not been identified. To identify mutations in lung SCC of non-smokers, we performed a genetic analysis using arrays comparative genomic hybridization (ArrayCGH). We analyzed 19 patients with lung SCC who underwent surgical treatment between April 2005 and April 2015. Clinical characteristics were reviewed, and DNA was extracted from fresh frozen lung cancer specimens. All of copy number alterations from ArrayCGH were validated using The Cancer Genome Atlas (TCGA) copy number variation (CNV) data of lung SCC. We examined the frequency of copy number changes according to the smoking status (non-smoker [n = 8] or smoker [n = 11]). We identified 16 significantly altered regions from ArrayCGH data, three gain and four loss regions overlapped with the TCGA lung squamous cell carcinoma (LUSC) patients. Within these overlapped significant regions, we detected 15 genes that have been reported in the Cancer Gene census. We also found that the proto-oncogene GAB2 (11q14.1) was significantly amplified in non-smokers patients and vice versa in both ArrayCGH and TCGA data. Immunohistochemical analyses showed that GAB2 protein was relatively upregulated in non-smoker than smoker tissues (37.5% vs. 9.0%, P = 0.007). GAB2 amplification may have an important role in the development of lung SCC in non-smokers. GAB2 may represent a potential biomarker for lung SCC in non-smokers. PMID:28960030

GAB2 Amplification in Squamous Cell Lung Cancer of Non-Smokers.

PubMed

Park, Yu Rang; Bae, Soo Hyeon; Ji, Wonjun; Seo, Eul Ju; Lee, Jae Cheol; Kim, Hyeong Ryul; Jang, Se Jin; Choi, Chang Min

2017-11-01

Lung squamous cell cancer (SCC) is typically found in smokers and has a very low incidence in non-smokers, indicating differences in the tumor biology of lung SCC in smokers and non-smokers. However, the specific mutations that drive tumor growth in non-smokers have not been identified. To identify mutations in lung SCC of non-smokers, we performed a genetic analysis using arrays comparative genomic hybridization (ArrayCGH). We analyzed 19 patients with lung SCC who underwent surgical treatment between April 2005 and April 2015. Clinical characteristics were reviewed, and DNA was extracted from fresh frozen lung cancer specimens. All of copy number alterations from ArrayCGH were validated using The Cancer Genome Atlas (TCGA) copy number variation (CNV) data of lung SCC. We examined the frequency of copy number changes according to the smoking status (non-smoker [n = 8] or smoker [n = 11]). We identified 16 significantly altered regions from ArrayCGH data, three gain and four loss regions overlapped with the TCGA lung squamous cell carcinoma (LUSC) patients. Within these overlapped significant regions, we detected 15 genes that have been reported in the Cancer Gene census. We also found that the proto-oncogene GAB2 (11q14.1) was significantly amplified in non-smokers patients and vice versa in both ArrayCGH and TCGA data. Immunohistochemical analyses showed that GAB2 protein was relatively upregulated in non-smoker than smoker tissues (37.5% vs. 9.0%, P = 0.007). GAB2 amplification may have an important role in the development of lung SCC in non-smokers. GAB2 may represent a potential biomarker for lung SCC in non-smokers. © 2017 The Korean Academy of Medical Sciences.

SOCS3 inhibits the pathological effects of IL-22 in non-melanoma skin tumor-derived keratinocytes.

PubMed

Madonna, Stefania; Scarponi, Claudia; Morelli, Martina; Sestito, Rosanna; Scognamiglio, Pasqualina Liana; Marasco, Daniela; Albanesi, Cristina

2017-04-11

Basal cell carcinomas (BCC) and squamous-cell carcinomas (SCC) are common malignancies in humans, caused by neoplastic transformation of keratinocytes of the basal or suprabasal layers of epidermis, respectively. Tumor-infiltrating lymphocytes (TILs) are frequently found in BCC and SCC, and functionally promote epithelial carcinogenesis. TILs secreting IL-22, in particular, participate to BCC and SCC growth by inducing keratinocyte proliferation and migration, as well as the expression of inflammatory, anti-apoptotic and pro-angiogenic genes.In this study, we identified SOCS3 as a valid candidate to be manipulated for suppressing tumorigenic functions in BCC and SCC. We found that SOCS3 and SOCS1 expression was reduced in vivo, in tumor lesions of BCC and SCC, as compared to other skin inflammatory conditions such as psoriasis, despite the high number of IL-22-secreting TILs. Moreover, IL-22 was not able to induce in vitro the transcriptional expression of SOCS3 in BCC-or SCC-derived keratinocytes, contrarily to healthy cells. Aimed at rescuing SOCS3 activity in these tumor contexts, a SOCS3-derived peptide, named KIR-ESS, was synthesized, and its ability in suppressing IL-22-induced responses was evaluated in healthy and transformed keratinocytes. We found that KIR-ESS peptide efficiently suppressed the IL-22 molecular signaling in keratinocytes, by acting on STAT3 and Erk1/2 cascade, as well as on the expression of STAT3-dependent downstream genes. Interestingly, after treatment with peptide, both healthy and transformed keratinocytes could no longer aberrantly proliferate and migrate in response to IL-22. Finally, treatment of athymic nude mice bearing SCC xenografts with KIR-ESS peptide concomitantly reduced tumor growth and activated STAT3 levels. As a whole, these data provides the rationale for the use in BCC and SCC skin tumors of SOCS3 mimetics, being able to inhibit the deleterious effects of IL-22 in these contexts.

SOCS3 inhibits the pathological effects of IL-22 in non-melanoma skin tumor-derived keratinocytes

PubMed Central

Madonna, Stefania; Scarponi, Claudia; Morelli, Martina; Sestito, Rosanna; Scognamiglio, Pasqualina Liana; Marasco, Daniela; Albanesi, Cristina

2017-01-01

Basal cell carcinomas (BCC) and squamous-cell carcinomas (SCC) are common malignancies in humans, caused by neoplastic transformation of keratinocytes of the basal or suprabasal layers of epidermis, respectively. Tumor-infiltrating lymphocytes (TILs) are frequently found in BCC and SCC, and functionally promote epithelial carcinogenesis. TILs secreting IL-22, in particular, participate to BCC and SCC growth by inducing keratinocyte proliferation and migration, as well as the expression of inflammatory, anti-apoptotic and pro-angiogenic genes. In this study, we identified SOCS3 as a valid candidate to be manipulated for suppressing tumorigenic functions in BCC and SCC. We found that SOCS3 and SOCS1 expression was reduced in vivo, in tumor lesions of BCC and SCC, as compared to other skin inflammatory conditions such as psoriasis, despite the high number of IL-22-secreting TILs. Moreover, IL-22 was not able to induce in vitro the transcriptional expression of SOCS3 in BCC-or SCC-derived keratinocytes, contrarily to healthy cells. Aimed at rescuing SOCS3 activity in these tumor contexts, a SOCS3-derived peptide, named KIR-ESS, was synthesized, and its ability in suppressing IL-22-induced responses was evaluated in healthy and transformed keratinocytes. We found that KIR-ESS peptide efficiently suppressed the IL-22 molecular signaling in keratinocytes, by acting on STAT3 and Erk1/2 cascade, as well as on the expression of STAT3-dependent downstream genes. Interestingly, after treatment with peptide, both healthy and transformed keratinocytes could no longer aberrantly proliferate and migrate in response to IL-22. Finally, treatment of athymic nude mice bearing SCC xenografts with KIR-ESS peptide concomitantly reduced tumor growth and activated STAT3 levels. As a whole, these data provides the rationale for the use in BCC and SCC skin tumors of SOCS3 mimetics, being able to inhibit the deleterious effects of IL-22 in these contexts. PMID:28445952

Management of canine corneal squamous cell carcinoma with lamellar keratectomy and strontium 90 plesiotherapy: 3 cases.

PubMed

Nevile, Jessica C; Hurn, Simon D; Turner, Andrew G; McCowan, Christina

2015-05-01

To report three cases of canine corneal squamous cell carcinoma (SCC) treated with strontium 90 beta radiation as an adjunct to surgical excision. Corneal SCC was excised with lamellar keratectomy. This was followed by local application of strontium 90 beta radiation. Available case follow-up times range from 3 to 50 months. One case suffered a recurrence 5 months following initial excision and strontium 90 treatment. Strontium 90 beta radiation has been used extensively as an adjunctive treatment for equine corneal SCC and in other canine ocular tumors; however, there is a paucity of information regarding use in canine corneal SCC. The cases presented here suggest its use following keratectomy may be helpful in preventing disease recurrence. At the dosage used, severe adverse effects were not observed. © 2014 American College of Veterinary Ophthalmologists.

Use of dairy herd improvement somatic cell information by Ohio dairy producers and their perceptions of mastitis.

PubMed

Miller, G Y; Eastridge, M L; Hueston, W D; Hoblet, K H

1988-08-01

A telephone survey was conducted of 149 current recipients of the Ohio DHIA SCC option, 30 past recipients of the SCC option, and 30 producers who had never received the SCC option. Producers were questioned to ascertain their knowledge of mastitis, how they used SCC information, their treatment and prevention of mastitis, and their use of veterinary services. Producers' perceptions of mastitis indicated a high awareness of the consequences of mastitis. However, 10% of producers on DHI still did not practice postmilking teat dipping, and 16% did not handle mastitic cows any differently during milking. Current recipients of SCC data used the data more frequently than did past recipients of the SCC data to evaluate mastitis treatment or control, choose cows to cull, identify cows to dry off early, indicate herd infection, and evaluate mastitis control. The major reason given by nonrecipients for never having enrolled in the SCC program was that they did not perceive a need for it. Further educational programs explaining SCC and its use to producers seems warranted.

Case–Control Study of Cutaneous Human Papillomaviruses in Squamous Cell Carcinoma of the Skin

PubMed Central

Iannacone, Michelle R.; Gheit, Tarik; Waterboer, Tim; Giuliano, Anna R.; Messina, Jane L.; Fenske, Neil A.; Cherpelis, Basil S.; Sondak, Vernon K.; Roetzheim, Richard G.; Michael, Kristina M.; Tommasino, Massimo; Pawlita, Michael; Rollison, Dana E.

2015-01-01

Background Cutaneous human papillomavirus (HPV) infection may be a risk factor for squamous cell carcinoma (SCC) of the skin. Methods To investigate the association between cutaneous HPV and SCC, a case–control study was conducted, including 173 SCC cases from a university dermatology clinic and 300 controls that screened negative for skin cancer. Serum antibodies against cutaneous HPV types in genera alpha, beta, gamma, mu, and nu were measured. Tumor tissue from 159 SCC cases was tested for the presence of DNA for genus-beta HPV types. Using logistic regression ORs and 95% confidence intervals (CI) were estimated for the associations between SCC and cutaneous HPV infection, adjusting for age and sex. The Bonferroni method was used to account for multiple comparisons. Results SCC was positively associated with seropositivity to any genus-beta HPV type (OR, 1.93; 95% CI, 1.23–3.02), particularly with types in species-1 (OR, 1.86; 95% CI, 1.22–2.85). Type-specific associations with SCC were observed for HPV 8 (OR, 1.80; 95% CI, 1.14–2.84), 17 (OR, 1.59; 95% CI, 1.02–2.49) and HPV 10 from genus-alpha (OR, 2.24; 95% CI, 1.04–4.85). None of the type-specific associations remained statistically significant after correction for multiple comparisons. When DNA-positive SCC cases were compared with controls, strong serologic associations were observed for HPVs 5 (OR, 3.48; 95% CI, 1.27–9.59), 17 (OR, 3.36; 95% CI, 1.29–8.72), and 24 (OR, 3.79; 95% CI, 1.24–11.5). Conclusion Genus-beta HPV infections were associated with SCC in our study population. Impact Identifying the role of cutaneous HPV infection in SCC may lead to improved characterization of high-risk individuals and the development of novel prevention strategies. PMID:22707711

Naturally occurring mastitis disrupts developmental competence of bovine oocytes.

PubMed

Roth, Z; Dvir, A; Kalo, D; Lavon, Y; Krifucks, O; Wolfenson, D; Leitner, G

2013-10-01

We examined the effects of naturally occurring mastitis on bovine oocyte developmental competence in vitro. Specifically, we investigated the effects of intramammary infection on the ovarian pool of oocytes (i.e., follicle-enclosed oocytes) and their ability to undergo in vitro maturation, fertilization, and further development to the blastocyst stage. Culled Holstein cows (n=50) from 9 commercial dairy farms in Israel were allotted to 3 groups according to somatic cell count (SCC) records of the last 3 monthly milk tests as well as of quarter samples collected before slaughter: (1) low SCC (n=7), (2) medium SCC (n=16), or (3) high SCC (n=27). Means of SCC values differed among low-, medium-, and high-SCC groups: 148,000, 311,000 and 1,813,000 cell/mL milk, respectively. Milk yield and days in milk did not differ among the 3 groups. Bacterial isolates included coagulase-negative staphylococci, Escherichia coli, Streptococcus dysgalactiae, or no bacteria found. Ovaries were collected at the abattoir and brought to the laboratory. Cumulus oocyte complexes were recovered separately from each cow and subjected individually to in vitro maturation and fertilization, followed by 8d in culture. The number of aspirated oocytes did not differ among groups, with a range of 17 to 21 oocytes per cow. The proportion of oocytes that cleaved into 2- to 4-cell-stage embryos (86.1 ± 3.4%) did not differ among groups. In contrast, mean percentages of embryos developed to the blastocyst stage on d 7 and 8 after fertilization were less in both medium- and-high SCC groups than in the low-SCC group (5.6 ± 2.3 and 4.1 ± 1.8 vs. 18.1 ± 4.6%, respectively). Additional analysis indicated that cleavage and blastocyst-formation rates did not differ among the bacterial types in the low-, medium-, and high-SCC groups. These are the first results to demonstrate that naturally occurring mastitis disrupts the developmental competence of the ovarian pool of oocytes, (i.e., oocytes at the germinal vesicle stage). The disruption was associated with elevation of SCC rather than bacterial type. The results may provide a partial explanation for the low fertility of cows that have contracted mastitic pathogens before insemination. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Oral cancer/endothelial cell fusion experiences nuclear fusion and acquisition of enhanced survival potential.

PubMed

Song, Kai; Song, Yong; Zhao, Xiao-Ping; Shen, Hui; Wang, Meng; Yan, Ting-Lin; Liu, Ke; Shang, Zheng-Jun

2014-10-15

Most previous studies have linked cancer-macrophage fusion with tumor progression and metastasis. However, the characteristics of hybrid cells derived from oral cancer and endothelial cells and their involvement in cancer remained unknown. Double-immunofluorescent staining and fluorescent in situ hybridization (FISH) were performed to confirm spontaneous cell fusion between eGFP-labeled human umbilical vein endothelial cells (HUVECs) and RFP-labeled SCC9, and to detect the expression of vementin and cytokeratin 18 in the hybrids. The property of chemo-resistance of such hybrids was examined by TUNEL assay. The hybrid cells in xenografted tumor were identified by FISH and GFP/RFP dual-immunofluoresence staining. We showed that SCC9 cells spontaneously fused with cocultured endothelial cells, and the resultant hybrid cells maintained the division and proliferation activity after re-plating and thawing. Such hybrids expressed markers of both parental cells and became more resistant to chemotherapeutic drug cisplatin as compared to the parental SCC9 cells. Our in vivo data indicated that the hybrid cells contributed to tumor composition by using of immunostaining and FISH analysis, even though the hybrid cells and SCC9 cells were mixed with 1:10,000, according to the FACS data. Our study suggested that the fusion events between oral cancer and endothelial cells undergo nuclear fusion and acquire a new property of drug resistance and consequently enhanced survival potential. These experimental findings provide further supportive evidence for the theory that cell fusion is involved in cancer progression. Copyright © 2014 Elsevier Inc. All rights reserved.

Immunolocalization of glioma-associated oncogene homolog 1 in non melanoma skin cancer.

PubMed

Bakry, Ola Ahmed; Samaka, Rehab Monir; Shoeib, Mohamed Abdel Moneim; Megahed, Doaa Mohamed

2015-04-01

Glioma-associated oncogene homolog (GLI)1 is involved in controlling cell proliferation and angiogenesis. The aim of this work was to explore its possible role in non-melanoma skin cancer pathogenesis through its immunohistochemical (IHC) expression in skin biopsies of these diseases and correlating this expression with the clinico-pathological parameters of the studied cases. Seventy-six cutaneous specimens were studied; 30 cases with basal cell carcinoma (BCC), 30 cases with squamous cell carcinoma (SCC) and 16 normal skin samples, from age- and gender-matched subjects, as a control group. GLI1 was expressed in all BCC cases and in 60% of SCC cases. All SCC cases showed cytoplasmic, while 70% of BCC cases showed nucleocytoplasmic immunoreactivity. It was over expressed in BCC and SCC compared to normal skin (p = 0.01 and 0.0006, respectively). Higher Histo (H) score in BCC cases was significantly associated with female gender (p = 0.04), multiple lesions, desmoplastic stromal reaction and stromal angiogenesis (p < 0.001 for all). Higher H score in SCC cases was significantly associated with scalp location, nodular type, recurrent lesions, high tumor grade, lymphovascular invasion (p = 0.004 for all), inflammatory stromal reaction (p = 0.01), lymph node involvement and absence of calcification (p = 0.001 for both). In conclusion, GLI1 may play a role in BCC pathogenesis through its role in cell proliferation, migration, and angiogenesis. Its upregulation and cytoplasmic localization in SCC may suggest that its role in tumor pathogenesis is through mechanisms other than Hedgehog pathway activation. Further studies are needed to clarify the exact molecular basis of its oncogenic action.

Geographic variation and risk of skin cancer in US women. Differences between melanoma, squamous cell carcinoma, and basal cell carcinoma.

PubMed

Qureshi, Abrar A; Laden, Francine; Colditz, Graham A; Hunter, David J

2008-03-10

Occurrences of melanoma, squamous cell carcinoma (SCC), and basal cell carcinoma (BCC) have been associated with varying geography. Our goal was to evaluate differences in risk of these skin cancers according to residence at varying UV indices at 3 time points. Prospective 1984-2002 study of 84 836 female nurses who lived in different UV index regions of the United States at birth and at 15 or 30 years of age. The outcome measure was diagnosis of melanoma, SCC, or BCC. During the 18-year study, 420 cases of melanoma, 863 cases of SCC, and 8215 cases of BCC occurred. At 30 years of age, age-adjusted risks for SCC were 1.47 (95% confidence interval [CI], 1.22-1.76) and 1.90 (95% CI, 1.51-2.36) for women residing in states with a UV index of 6 (medium) and 7 or more (high), respectively. Although elevated, the age-adjusted risk of BCC at 30 years of age associated with residence in these states was substantially less. Although the risk of melanoma was not elevated for women living in these states at 30 years of age, it was significantly elevated among women living in states with UV indices of 6 at birth and at 15 years of age. There was no material change in risk estimates with multivariate adjustment. For women who reported living in states with UV indices of 7 or more at all 3 time points, the multivariate risk of SCC was highest. The risk of SCC is independently affected by residence in locations with medium and high UV indices; the gradient of risk is weaker for BCC; and the risk of melanoma does not change significantly across this gradient.

Reliability and Agreement Between Metrics of Cone Spacing in Adaptive Optics Images of the Human Retinal Photoreceptor Mosaic.

PubMed

Giannini, Daniela; Lombardo, Giuseppe; Mariotti, Letizia; Devaney, Nicholas; Serrao, Sebastiano; Lombardo, Marco

2017-06-01

To assess reliability and agreement among three metrics used to evaluate the distribution of cell distances in adaptive optics (AO) images of the cone mosaic. Using an AO flood illumination retinal camera, we acquired images of the cone mosaic in 20 healthy subjects and 12 patients with retinal diseases. The three spacing metrics studied were the center-to-center spacing (Scc), the local cone spacing (LCS), and the density recovery profile distance (DRPD). Each metric was calculated in sampling areas of different sizes (64 × 64 μm and 204 × 204 μm) across the parafovea. Both Scc and LCS were able to discriminate between healthy subjects and patients with retinal diseases; DRPD did not reliably detect any abnormality in the distribution of cell distances in patients with retinal diseases. The agreement between Scc and LCS was high in healthy subjects (intraclass correlation coefficient [ICC] ≥ 0.79) and moderate in patients with retinal diseases (ICC ≤ 0.51). The DRPD had poor agreement with Scc (ICC ≤ 0.47) and LCS (ICC ≤ 0.37). The correlation between the spacing metrics of the two sampling areas was greater in healthy subjects than in patients with retinal diseases. The Scc and LCS provided interchangeable estimates of cone distance in AO retinal images of healthy subjects but could not be used interchangeably when investigating retinal diseases with significant cell reflectivity loss (≥30%). The DRPD was unreliable for describing cell distance in a human retinal cone mosaic and did not correlate with Scc and LCS. Caution is needed when comparing spacing metrics evaluated in sampling areas of different sizes.

Haematuria as an uncommon initial presenting symptom of metastatic squamous cell carcinoma (SCC) to kidney

PubMed Central

Kawsar, Hameem I; Spiro, Timothy P; Daw, Hamed A

2011-01-01

A 47-year-old female presented with a 2-week history of painless haematuria. Urine dipstick showed moderate leucocytes. Blood and urine cultures were negative and cytology was negative for malignant cells. Flexible cystoscopy was negative for any bladder pathology. An ultrasonogram of the abdomen showed a mass in the left kidney. CT showed a mass-like lesion within the left kidney suspicious for renal carcinoma, and cavitary lesions in both lungs. Biopsy of the lung showed clusters of atypical cells suspicious for squamous cell carcinoma (SCC), and left kidney lesion showed malignant cells derived from SCC. A whole body positron emission tomography/CT showed lesions in the lungs, left kidney and skeleton. Complete clinical examination, laboratory and imaging studies did not reveal any site of primary tumour in any part of the body. Haematuria is a very unusual initial presentation of metastatic tumour to kidney. PMID:22688475

Invited review: effect of udder health management practices on herd somatic cell count.

PubMed

Dufour, S; Fréchette, A; Barkema, H W; Mussell, A; Scholl, D T

2011-02-01

A systematic review of the scientific literature on relationships between management practices used on dairy farms and herd somatic cell count (SCC) was undertaken to distinguish those management practices that have been consistently shown to be associated with herd SCC from those lacking evidence of association. Relevant literature was identified using a combination of database searches (PubMed, Medline, CAB, Agricola, and Web of Science) and iterative screening of references. To be included in the review, a manuscript had to be published after 1979 in French, English, or Dutch; study design had to be other than case report or case series; herds studied had to be composed of ≥ 40 milking cows producing on average ≥ 7,000kg of milk in 305 d; interventions studied had to be management practices applied at the herd level and used as udder health control strategies; and SCC had to be measured using electronic cell counting methods. The 36 manuscripts selected were mainly observational cross-sectional studies; 8 manuscripts dealt exclusively with automatic milking systems and 4 with management of calves and heifers and its effect on SCC in early lactation heifers. Most practices having consistent associations with SCC were related to milking procedures: wearing gloves during milking, using automatic take-offs, using postmilking teat dipping, milking problem cows last, yearly inspection of the milking system, and use of a technique to keep cows standing following milking; all were consistently associated with lower herd SCC. Other practices associated with lower SCC were the use of a freestall system, sand bedding, cleaning the calving pen after each calving, surveillance of dry-cow udders for mastitis, use of blanket dry-cow therapy, parenteral selenium supplementation, udder hair management, and frequent use of the California Mastitis Test. Regarding SCC of heifers, most of the consistent associations reported were related to interventions made during the peripartum period. Studies on automatic milking systems have frequently reported elevation of the herd SCC following transition to the new system. These elevations seemed to be mediated both by the lack of monitoring of chronically infected cows and by an elevated incidence of intramammary infections. By assembling the results reported in many different studies, this review generates a more comprehensive understanding of the management practices influencing SCC and highlights areas of SCC control knowledge that lack evidence of effectiveness. Copyright © 2011 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Donor-derived stem-cells and epithelial mesenchymal transition in squamous cell carcinoma in transplant recipients.

PubMed

Verneuil, Laurence; Leboeuf, Christophe; Bousquet, Guilhem; Brugiere, Charlotte; Elbouchtaoui, Morad; Plassa, Louis-François; Peraldi, Marie-Noelle; Lebbé, Celeste; Ratajczak, Philippe; Janin, Anne

2015-12-08

Skin squamous-cell-carcinoma (SCC), is the main complication in long-term kidney-transplant recipients, and it can include donor-derived cells. Preclinical models demonstrated the involvement of epithelial mesenchymal transition (EMT) in the progression of skin SCC, and the role of Snail, an EMT transcription factor, in cancer stem-cell survival and expansion.Here, we studied stem-cells and EMT expression in SCCs and concomitant actinic keratoses (AK) in kidney-transplant recipients. In SCC and AK in 3 female recipients of male kidney-transplants, donor-derived Y chromosome in epidermal stem cells was assessed using combined XY-FISH/CD133 immunostaining, and digital-droplet-PCR on laser-microdissected CD133 expressing epidermal cells.For EMT study, double immunostainings of CD133 with vimentin or snail and slug, electron microscopy and immunostainings of keratinocytes junctions were performed. Digital droplet PCR was used to check CDH1 (E-cadherin) expression level in laser-microdissected cells co-expressing CD133 and vimentin or snail and slug.The numbers of Y-chromosome were assessed using digital droplet PCR in laser-microdissected cells co-expressing CD133 and vimentin, or snail and slug, and in CD133 positive cells not expressing any EMT maker. We identified donor-derived stem-cells in basal layers and invasive areas in all skin SCCs and in concomitant AKs, but not in surrounding normal skin.The donor-derived stem-cells expressed the EMT markers, vimentin, snail and slug in SCCs but not in AKs. The expression of the EMT transcription factor, SNAI1, was higher in stem-cells when they expressed vimentin. They were located in invasive areas of SCCs. In these areas, the expressions of claudin-1 and desmoglein 1 were reduced or absent, and within the basal layer there were features of basal membrane disappearance.Donor-derived stem cells were in larger numbers in stem cells co-expressing vimentin or snail and slug than in stem cells not expressing any EMT marker. We identified here donor-derived stem cells within skin SCC in kidney-transplant recipients. They were located in invasive areas of SCC and had EMT characteristics.

HA-1077 inhibits cell migration/invasion of oral squamous cell carcinoma.

PubMed

Moreira Carboni, Simone de Sales Costa; Rodrigues Lima, Nathália Alves; Pinheiro, Nanci Mendes; Tavares-Murta, Beatriz Martins; Crema, Virgínia Oliveira

2015-10-01

Oral squamous cell carcinoma (OSCC) is the most malignant lesion occurring in the head and neck. The Rho-kinases (ROCKs), effectors of Rho proteins, are involved in actin cytoskeletal organization, cell migration, and maintenance cortex. The HA-1077 inhibits the ROCKs. This study aimed to evaluate the effect of treatment with HA-1077 on cell motility in SCC-4 cells, a cell line originating from human OSCC. F-actin of SCC-4 cells treated or not with HA-1077 (1, 50 and 100 μmol/l), and also HA-1077 50 μmol/l and/or inhibitors Y-27632 30 μmol/l was stained with rhodamine-conjugated phalloidin and analyzed by confocal microscopy. Approximately 1×10 cells/well, control and treated with HA-1077 (25, 50, and 100 μmol/l) were added to the migration plate assay. In addition, 1×10 cells/well, control and treated with HA-1077 50 μmol/l, were tested by invasion assays (plate coated with Matrigel). The inhibition of ROCKs with HA-1077 and/or Y-27632 leads to morphological changes, affecting the organization of the actin. The inhibitory effect of HA-1077 (P<0.0001) was dose dependent as the number of cells migrated at 100 μmol/l was statistically different: 25 μmol/l (P<0.0001) and 50 μmol/l (P<0.01). The number of cells treated with HA-1077 50 μmol/l decreased compared with control cells that invaded through Matrigel (P<0.0001). This study shows an inhibitory effect of HA-1077 on cell migration and invasion, suggesting that the use of HA-1077 can be a potential therapy for OSCC.

Analysis of full coding sequence of the TP53 gene in invasive vulvar cancers: Implications for therapy.

PubMed

Kashofer, Karl; Regauer, Sigrid

2017-08-01

This study evaluates the frequency and type of TP53 gene mutations and HPV status in 72 consecutively diagnosed primary invasive vulvar squamous cell carcinomas (SCC) during the past 5years. DNA of formalin-fixed and paraffin embedded tumour tissue was analysed for 32 HPV subtypes and the full coding sequence of the TP53 gene, and correlated with results of p53 immunohistochemistry. 13/72 (18%) cancers were HPV-induced squamous cell carcinomas, of which 1/13 (8%) carcinoma harboured a somatic TP53 mutation. Among the 59/72 (82%) HPV-negative cancers, 59/72 (82%) SCC were HPV-negative with wild-type gene in 14/59 (24%) SCC and somatic TP53 mutations in 45/59 (76%) SCC. 28/45 (62%) SCC carried one (n=20) or two (n=8) missense mutations. 11/45 (24%) carcinomas showed a single disruptive mutation (3× frame shift, 7× stop codon, 1× deletion), 3/45 SCC a splice site mutation. 3/45 (7%) carcinomas had 2 or 3 different mutations. 18 different "hot spot" mutations were observed in 22/45 cancers (49%; 5× R273, 3× R282; 2× each Y220, R278, R248). Immunohistochemical p53 over expression was identified in most SCC with missense mutations, but not in SCC with disruptive TP53 mutations or TP53 wild-type. 14/45 (31%) patients with TP53 mutated SCC died of disease within 12months (range 2-24months) versus 0/13 patients with HPV-induced carcinomas and 0/14 patients with HPV-negative, TP53 wild-type carcinomas. 80% of primary invasive vulvar SCC were HPV-negative carcinomas with a high frequency of disruptive mutations and "hot spot" TP53 gene mutations, which have been linked to chemo- and radioresistance. The death rate of patients with p53 mutated vulvar cancers was 31%. Immunohistochemical p53 over expression could not reliably identify SCC with TP53 gene mutation. Pharmacological therapies targeting mutant p53 will be promising strategies for personalized therapy in patients with TP53 mutated vulvar cancers. Copyright © 2017. Published by Elsevier Inc.

Human papillomavirus in tonsillar squamous cell carcinomas from Guatemala and Brazil.

PubMed

Piña, Alicia Rumayor; Jimenez, Laísa Simakawa; Mariano, Fernanda Viviane; de Andrade, Bruno Augusto Benevenuto; Carlos, Román; Altemani, Albina; de Almeida, Oslei Paes

2016-04-01

A subgroup of tonsillar squamous cell carcinoma (SCC) is associated with human papillomavirus (HPV). Nevertheless, the prevalence of HPV seems to be variable in different regions and ethnic groups. There are no reports of HPV in tonsillar carcinomas in Guatemala, and data from Brazil are scarce. The aim of this study is to analyze and compare HPV presence in samples of tonsillar SCC from these countries. This study describes the histologic features, expression of p16 by immunohistochemistry (IHC), and HPV by in situ hybridization (ISH) in 13 Guatemalan and 13 Brazilian patients. All cases of tonsillar SCC from Guatemala were positive for p16, 92% expressed HPV by ISH, and 75% corresponded to the high-risk genotype 16/18. From the Brazilian patients, only four expressed p16, and all were negative for HPV. Cases from Guatemala, which were mostly nonkeratinizing SCC and originated from the crypt/reticular epithelium of the tonsil, had high-risk integrated HPV, whereas in Brazilian cases, which were mostly keratinizing SCC that originated from the surface epithelium, there was no association with HPV. Copyright © 2016 Elsevier Inc. All rights reserved.

No association between infections, HLA type and other transplant-related factors and risk of cutaneous squamous cell carcinoma in solid organ transplant recipients.

PubMed

Ingvar, Åsa; Ekström Smedby, Karin; Lindelöf, Bernt; Fernberg, Pia; Bellocco, Rino; Tufveson, Gunnar; Höglund, Petter; Adami, Johanna

2012-11-01

Recipients of solid organ transplants are at a markedly increased risk of cutaneous squamous cell carcinoma (SCC). We investigated potential associations between post-transplant infections, HLA type, and other transplant-related factors and risk of SCC, taking immuno-suppressive treatment into account. A population-based case-control study was conducted. All patients who developed SCC during follow-up (1970-1997) were eligible as cases (n = 207). Controls (n = 189) were individually matched to the cases on age and calendar period of transplantation. Detailed exposure information was collected through an extensive, blinded review of medical records. Odds ratios were computed with conditional logistic regression. There were no significant associations with any infectious agents, or with number and timing of infections, specific HLA-type, donor characteristics, or other transplant characteristics and risk of post-transplant SCC. These results suggest that risk of post-transplant SCC is neither closely related to specific post-transplant infectious disorders, nor to the infectious load or specific HLA types.

Height, height-related SNPs, and risk of non-melanoma skin cancer.

PubMed

Li, Xin; Liang, Liming; Feng, Yen-Chen Anne; De Vivo, Immaculata; Giovannucci, Edward; Tang, Jean Y; Han, Jiali

2017-01-03

Adult height has been associated with risk of several site-specific cancers, including melanoma. However, less attention has been given to non-melanoma skin cancer (NMSC). We prospectively examined the risk of squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) in relation to adult height in the Nurses' Health Study (NHS, n=117 863) and the Health Professionals Follow-up Study (HPFS, n=51 111). We also investigated the relationships between height-related genetic markers and risk of BCC and SCC in the genetic data sets of the NHS and HPFS (3898 BCC cases, and 8530 BCC controls; 527 SCC cases, and 8962 SCC controls). After controlling for potential confounding factors, the hazard ratios were 1.09 (95% CI: 1.02, 1.15) and 1.10 (95% CI: 1.07, 1.13) for the associations between every 10 cm increase in height and risk of SCC and BCC respectively. None of the 687 height-related single-nucleotide polymorphisms (SNPs) was significantly associated with the risk of SCC or BCC, nor were the genetic scores combining independent height-related loci. Our data from two large cohorts provide further evidence that height is associated with an increased risk of NMSC. More studies on height-related genetic loci and early-life exposures may help clarify the underlying mechanisms.

Influence of the site of origin on the outcome of squamous cell carcinoma of the maxilla-oral versus sinus.

PubMed

Bobinskas, A M; Wiesenfeld, D; Chandu, A

2014-02-01

The maxilla may be affected by squamous cell carcinoma (SCC) from both oral and sinus sites. We sought to determine whether the site of origin of the maxillary tumour, oral as compared to sinus, influences survival. Univariate Kaplan-Meier and multivariate Cox proportional hazard models analysis of 58 patients with SCC involving the maxilla, treated with curative intent, was conducted. The overall 5-year disease-free survival for the group was 41.7%. Five-year disease-free survival for oral subsite SCC was 56.8%, while for sinus subsite was only 21.6%. Univariate analysis found SCC of sinus origin to be associated with a poorer prognosis, however this was not confirmed on multivariate analysis. T-stage and positive margins were found to be the only independent risk factors. For SCC of the maxilla, sinus origin of the tumour per se does not confer a poorer prognosis; however, as a result of the complex anatomy of the midface, these tumours can present at an advanced stage, while surgical control of the disease can be more difficult, especially posteriorly. Tumour size and positive margins were the determinants of a poor prognosis in this group of patients with maxillary SCC. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

S100A8/A9 Stimulates Keratinocyte Proliferation in the Development of Squamous Cell Carcinoma of the Skin via the Receptor for Advanced Glycation-End Products

PubMed Central

Iotzova-Weiss, Guergana; Dziunycz, Piotr J.; Freiberger, Sandra N.; Läuchli, Severin; Hafner, Jürg; Vogl, Thomas; French, Lars E.; Hofbauer, Günther F. L.

2015-01-01

Squamous cell carcinoma (SCC) is the most common neoplasm in organ transplant recipients (OTR) on long-term immunosuppression and occurs 60- to 100-fold more frequently than in the general population. Here, we present the receptor for advanced glycation end products (RAGE) and S100A8/A9 as important factors driving normal and tumor keratinocyte proliferation. RAGE and S100A8/A9 were transcriptionally upregulated in SCC compared to normal epidermis, as well as in OTR compared to immunocompetent patients (IC) with SCC. The proliferation of normal and SCC keratinocytes was induced by exposure to exogenous S100A8/A9 which in turn was abolished by blocking of RAGE. The migratory activities of normal and SCC keratinocytes were also increased upon exposure to S100A8/A9. We demonstrated that exogenous S100A8/A9 induces phosphorylation of p38 and SAPK/JNK followed by activation of ERK1/2. We hypothesize that RAGE and S100A8/A9 contribute to the development of human SCC by modulating keratinocyte growth and migration. These processes do not seem to be impaired by profound drug-mediated immunosuppression in OTR. PMID:25811984

Fibroblast Senescence and Squamous Cell Carcinoma: How wounding therapies could be protective

PubMed Central

Travers, Jeffrey B.; Spandau, Dan F; Lewis, Davina A.; Machado, Christiane; Kingsley, Melanie; Mousdicas, Nico; Somani, Ally-Khan

2014-01-01

Background Squamous cell carcinoma (SCC), which has one of the highest incidences of all cancers in the United States, is an age-dependent disease as the majority of these cancers are diagnosed in people over 70 years of age. Recent findings have led to a new hypothesis on the pathogenesis of SCC. Objectives To evaluate the potential of preventive therapies to reduce the incidence of SCC in at-risk geriatric patients. Materials and Methods Survey of current literature on wounding therapies to prevent SCCs. Results This new hypothesis of SCC photocarcinogenesis states that senescent fibroblasts accumulate in geriatric dermis resulting in a reduction in dermal insulin-like growth factor-1 (IGF-1) expression. This lack of IGF-1 expression sensitizes epidermal keratinocytes to fail to suppress UVB-induced mutations leading to increased proclivity to photocarcinogenesis. Recent evidence suggests that dermal wounding therapies, specifically dermabrasion and fractionated laser resurfacing, can decrease the proportion of senescent dermal fibroblasts, increase dermal IGF-1 expression, and correct the inappropriate UVB response found in geriatric skin, thus protecting geriatric keratinocytes from UVB-induced SCC initiation. Conclusions In this review, we will discuss the translation of pioneering basic science results implicating commonly used dermal fibroblast rejuvenation procedures as preventative treatments for SCC. PMID:23437969

Evaluation of Microvascularity by CD34 Expression in Esophagus and Oral Squamous Cell Carcinoma.

PubMed

Shahsavari, Fatemeh; Farhadi, Sareh; Sadri, Donia; Sedehi, Marzieh

2015-06-01

The present study was scheduled to evaluate microvascularity by CD34 expression in esophagus and oral squamous cell carcinoma. This study was scheduled using 40 paraffin blocked samples including 20 of oral SCC and 20 of esophagus ones and Immunohistochemical staining was conducted using CD34 monoclonal antibody. Exact fisher test was used to evaluate frequency of expression between two studied groups. There was significant correlation between age and tumor size with CD34 expression in oral SCC samples (p < 0.05) and no significant correlation between sex and tumor differentiation level (grading) (p > 0.05). Also, there was no significant correlation between age, sex, tumor size and tumor differentiation level (grading) with CD34 expression in esophagus SCC samples (p > 0.05). There was no significant difference of CD34 expression frequency in oral and esophagus SCC (p = 0/583). Finally, CD34 expression was reported 'high' for major cases of esophagus and oral SCCs. It seems, other angiogenetic or nonangiogenetic factors except CD34 may play more important role and explain the different clinical behavior of SCC at recent different locations. Other factors would be considered along with CD34 expression to interpret different clinical behavior of SCC at recent different locations.

The burden of non-melanoma skin cancers in Auckland, New Zealand.

PubMed

Pondicherry, Ashwini; Martin, Richard; Meredith, Ineke; Rolfe, Jack; Emanuel, Patrick; Elwood, Mark

2018-01-19

As the New Zealand Cancer Registry does not require mandatory reporting of non-melanoma skin cancers (NMSC), basal cell carcinomas (BCC) and squamous cell carcinomas (SCC), the clinical burden of these diseases is unknown. A retrospective review of all patients with histopathology performed allowed us to estimate invasive BCC and SCC in the Auckland region in 2008 (population 1.44 million). During this period, a total of 21 236 NMSC were diagnosed among 13 996 patients, consisting of 5611 SCC lesions (26%) and 15 525 (74%) BCC. The Auckland incidence rates per 100 000 were 425 for SCC and 1177 for BCC. The overall rate of NMSC per 100 000 was 1906.5 (standardised to the census data of Australia 2001); 1385 for BCC and 522 for SCC. Using published data on incidence trends and population growth, we estimate that 29 000-33 000 NMSC would have been excised in Auckland in 2016, and 78 000-87 000 in New Zealand. Auckland has the highest reported incidence of invasive NMSC in the world. We believe that high-risk cutaneous SCC and complex BCC should be recorded. Our study provides information for clinicians and health economists on the scale of the problem. © 2018 The Australasian College of Dermatologists.

Milk amyloid A as a biomarker for diagnosis of subclinical mastitis in cattle

PubMed Central

Hussein, Hany Ahmed; El-Razik, Khaled Abd El-Hamid Abd; Gomaa, Alaa Mohamed; Elbayoumy, Mohamed Karam; Abdelrahman, Khaled A.; Hosein, H. I.

2018-01-01

Background and Aim: Mastitis is one of the most vital noteworthy monetary risks to dairy ranchers and affects reproductive performance in dairy cattle. However, subclinical mastitis (SCM) negatively affects milk quality and quantity and associated with economic losses as clinical mastitis. It is recognizable only by additional testing. Somatic cell count (SCC) is currently used worldwide for the screening of intramammary infection (IMI) infections. However, somatic cells (SC) are affected by numerous factors and not always correlate with infection of the udder. Therefore, the aim of the present study was to evaluate the milk amyloid A (MAA) in the milk of normal and SCM cows and compare the sensitivity of both MAA secretion and SCC in response to mammary gland bacterial infection. Materials and Methods: A total of 272 quarter milk samples collected from 68 Friesian cows after clinical examination for detection of clinical mastitis were employed in this study. All quarter milk samples (272) were subjected to bacteriological examination, while SCs were assessed in samples (220). Following SCC estimation and bacteriological examination, the apparently normal quarter milk samples were categorized into 7 groups and MAA concentration was estimated in normal and subclinical mastitic milk samples. Results: Prevalence of clinical mastitis was 19.12 % (52 quarters), while 80.88 % (220 quarters) were clinically healthy with normal milk secretion. Of those 220 clinically healthy quarter milk samples, 72 (32.73%) showed SCM as detected by SCC (SCC ≥500,000 cells/ml). The most prevalent bacteria detected in this study were streptococci (48.53%), Staphylococcus aureus (29.41%), Escherichia coli (36.76%), and coagulase-negative staphylococci (11.76%). Results of MAA estimation revealed a strong correlation between MAA secretion level and SCC in agreement with the bacteriological examination. Interestingly, there was a prompt increase in MAA concentration in Group III (G III) (group of milk samples had SCC ≤200,000 cells/ml and bacteriologically positive) than Group I (G I) (group of milk samples with SCC ≤500,000 cells/ml and bacteriologically negative), as MAA concentration in G III was about 4 times its concentration in G I. Conclusion: Our study provides a strong evidence for the significance of MAA measurement in milk during SCM, and MAA is more sensitive to IMI than SCC. This can be attributed to rapid and sensitive marker of inflammation. The advantage of MAA over other diagnostic markers of SCM is attributed the minute or even undetectable level of MAA in the milk of healthy animals, it is not influenced by factors other than mastitis, and could be estimated in preserved samples. Therefore, we recommend that estimation of MAA concentration in milk is a more useful diagnostic tool than SCC to detect SCM and to monitor the udder health in dairy cattle. PMID:29479155

Folliculocentric squamous cell carcinoma with tricholemmal differentiation: a reappraisal of tricholemmal carcinoma.

PubMed

Misago, N; Toda, S; Narisawa, Y

2012-07-01

The diagnostic criteria for tricholemmal carcinoma remain controversial, and even the existence of tricholemmal carcinoma has been the subject of debate. Follicular (infundibular) squamous cell carcinoma (SCC) is a distinctive subset of SCC, which develops solely with folliculocentricity, and displays the features of conventional SCC without tricholemmal differentiation. To examine the existence of pure folliculocentric SCCs showing tricholemmal differentiation, that is, tricholemmal carcinoma. In total, 812 SCCs were examined, and those meeting the following diagnostic criteria were selected: (i) pure folliculocentricity without any associated Bowen's disease or actinic keratosis; (ii) composition primarily of lightly eosinophilic cells or clear cells containing glycogen; (iii) columnar lightly eosinophilic or clear cells aligned in a palisade along a discernible basement membrane; (iv) tricholemmal keratinization; (v) glycogen contained within the pale/clear cells; and (vi) cytological atypia and or infiltrative growth. We also evaluated whether the immunohistochemical profile [cytokeratin (CK)1, CK10, CK17, CD34 and D2-40] seen in normal hair follicles was retained in the selected lesions. Only two lesions met the criteria. The immunohistochemical profile of the normal outer root sheath cells was generally retained in these lesions, except for CD34. Tricholemmal carcinoma is a rare occurrence, but it does exist, and at least one type of tricholemmal carcinoma is considered to be related to follicular (infundibular) SCC. © The Author(s). CED © 2012 British Association of Dermatologists.

Suppression of E-cadherin function drives the early stages of Ras-induced squamous cell carcinoma through up-regulation of FAK and Src

PubMed Central

Alt-Holland, Addy; Sowalsky, Adam; Szwec-Levin, Yonit; Shamis, Yulia; Hatch, Harold; Feig, Larry A.; Garlick, Jonathan A.

2011-01-01

Advanced stages of epithelial carcinogenesis involve the loss of intercellular adhesion, but it remains unclear how proteins that regulate alterations in cell-cell and cell-matrix adhesion are deregulated to promote the early stages of cancer development. To address this, a three-dimensional human tissue model that mimics the incipient stages of Squamous Cell Carcinoma (SCC) was used to study how E-cadherin suppression promotes tumor progression in Ras-expressing human keratinocytes. We found that E-cadherin suppression triggered elevated mRNA and protein expression levels of Focal Adhesion Kinase (FAK), and increased FAK and Src activities above the level seen in Ras-expressing E-cadherin-competent keratinocytes. sh-RNA-mediated depletion of FAK and Src restored E-cadherin expression levels by increasing its stability in the membrane, and blocked tumor cell invasion in tissues. Surface transplantation of these tissues to mice resulted in reversion of the tumor phenotype to low-grade tumor islands in contrast to control tissues that manifested an aggressive, high-grade SCC. These findings suggest that the tumor-promoting effect of E-cadherin suppression, a common event in SCC development, is exacerbated by enhanced E-cadherin degradation induced by elevated FAK and Src activities. Furthermore, they imply that targeting FAK or Src in human epithelial cells with neoplastic potential may inhibit the early stages of SCC. PMID:21716326

Mutational analysis of cutaneous squamous cell carcinomas and verrucal keratosis in patients taking BRAF inhibitors.

PubMed

Anforth, Rachael; Tembe, Varsha; Blumetti, Tatiana; Fernandez-Peñas, Pablo

2012-09-01

B-RAF inhibitors (BRAFi) have been shown to improve rates of overall and progression-free survival in patients with stage IV metastatic melanoma positive for the BRAF V600E mutation. However, the main drawback is the development of verrucal keratosis (hyperkeratotic papules with verruca-like characteristics with benign histological findings) and cutaneous squamous cell carcinomas (cuSCC). We have found upstream mutations in RAS as well as PIK3CA in both verrucal keratosis and cuSCC. This suggests that verrucal keratosis is an early clinical presentation of cuSCC in patients on BRAFi. © 2012 John Wiley & Sons A/S.

Introducing a novel highly prognostic grading scheme based on tumour budding and cell nest size for squamous cell carcinoma of the uterine cervix.

PubMed

Jesinghaus, Moritz; Strehl, Johanna; Boxberg, Melanie; Brühl, Frido; Wenzel, Adrian; Konukiewitz, Björn; Schlitter, Anna M; Steiger, Katja; Warth, Arne; Schnelzer, Andreas; Kiechle, Marion; Beckmann, Matthias W; Noske, Aurelia; Hartmann, Arndt; Mehlhorn, Grit; Koch, Martin C; Weichert, Wilko

2018-04-01

A novel histopathological grading system based on tumour budding and cell nest size has recently been shown to outperform conventional (WHO-based) grading algorithms in several tumour entities such as lung, oral, and oesophageal squamous cell carcinoma (SCC) in terms of prognostic patient stratification. Here, we tested the prognostic value of this innovative grading approach in two completely independent cohorts of SCC of the uterine cervix. To improve morphology-based grading, we investigated tumour budding activity and cell nest size as well as several other histomorphological factors (e.g., keratinization, nuclear size, mitotic activity) in a test cohort (n = 125) and an independent validation cohort (n = 122) of cervical SCC. All parameters were correlated with clinicopathological factors and patient outcome. Small cell nest size and high tumour budding activity were strongly associated with a dismal patient prognosis (p < 0.001 for overall survival [OS], disease-specific survival, and disease-free survival; test cohort) in both cohorts of cervical SCC. A novel grading algorithm combining these two parameters proved to be a highly effective, stage-independent prognosticator in both cohorts (OS: p < 0.001, test cohort; p = 0.001, validation cohort). In the test cohort, multivariate statistical analysis of the novel grade revealed that the hazard ratio (HR) for OS was 2.3 for G2 and 5.1 for G3 tumours compared to G1 neoplasms (p = 0.010). In the validation cohort, HR for OS was 3.0 for G2 and 7.2 for G3 tumours (p = 0.012). In conclusion, our novel grading algorithm incorporating cell nest size and tumour budding allows strongly prognostic histopathological grading of cervical SCC superior to WHO-based grading. Therefore, our data can be regarded as a cross-organ validation of previous results demonstrated for oesophageal, lung, and oral SCC. We suggest this grading algorithm as an additional morphology-based parameter for the routine diagnostic assessment of this tumour entity. © 2018 The Authors The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and Ireland and John Wiley & Sons Ltd.

Occupation and keratinocyte cancer risk: a population-based case-control study.

PubMed

Marehbian, Josh; Colt, Joanne S; Baris, Dalsu; Stewart, Patricia; Stukel, Therese A; Spencer, Steven K; Karagas, Margaret R

2007-10-01

The aim of our study was to identify occupations associated with increased risk of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). We conducted a population-based case-control study of BCC and SCC in New Hampshire. Cases (n = 599 BCC, n = 290 SCC) and controls (n = 524) completed a self-administered residence and work history questionnaire and personal interview regarding major risk factors for skin cancer. Reported jobs were coded using the Standardized Occupational Classification system (SOC). Odds ratios (ORs) and confidence intervals (CIs) for BCC and SCC were calculated for men and women separately using unconditional logistic regression models taking into account age, education, skin reaction to sun, history of painful sunburns, time spent outdoors, and for SCC, smoking. Among men, we observed elevated risks of both BCC and SCC among groundskeepers and gardeners, except farm (SOC 5622). We also found that garage and service station-related occupations (SOCs 873) and to some extent food/beverage preparation/service occupations (SOC 521) were associated with BCC risk among men. Women in health services occupations (SOC 523) had elevated risks for both tumors, especially for BCC. Additionally, administrative support (SOC 46/47) occupations were related to BCC risk among women. Other occupations were associated with excess risks, but without consistent trends by duration of employment. We observed several occupations associated with elevated BCC and SCC risk. These results resemble reported findings for cutaneous melanoma and are generally consistent with the few available studies on keratinocyte cancers.

The Prevalence of Lichen Sclerosus in Patients With Vulvar Squamous Cell Carcinoma.

PubMed

Davick, Jonathan J; Samuelson, Megan; Krone, James T; Stockdale, Colleen K

2017-07-01

Women with vulvar lichen sclerosus (LS) have an increased risk of developing differentiated vulvar intraepithelial neoplasia and vulvar squamous cell carcinoma (SCC). Our primary aim was to determine the prevalence of LS among women with vulvar SCC. All patients who underwent excision for invasive SCC of the vulva from January 1, 2009 to December 31, 2013 were identified by searching our institution's electronic laboratory information system (n=111). The vulvar excision specimens from these patients were reviewed for the presence of adjacent LS. The grade of the SCC and clinical data were also documented for each case. The proportion of vulvar SCCs with adjacent LS identified on the excision specimen was 0.29 (95% confidence interval, 0.21-0.38). The proportion of patients in our study population who have ever had a histopathologic diagnosis of LS was 0.36 (95% confidence interval, 0.28-0.45). The presence of LS was not associated with the grade of the adjacent SCC. Patients with synchronous LS on excision were older on average than patients without LS. Tobacco users in our population were more likely to have a history of lower genital tract dysplasia, more likely to be younger, and less likely to have LS identified on the vulvar SCC excision specimen. Given the strong association between LS, differentiated vulvar intraepithelial neoplasia, and vulvar SCC, we recommend careful evaluation of these patients from a clinical and pathologic standpoint.

Immunohistochemical patterns of ProEx C in vulvar squamous lesions: detection of overexpression of MCM2 and TOP2A.

PubMed

Chen, Hui; Gonzalez, Jorge L; Brennick, Jeoffry B; Liu, Miaoliang; Yan, Shaofeng

2010-09-01

Two major subtypes of vulvar squamous cell carcinomas (SCC) have been described. Basaloid and warty SCC are human papillomavirus-related and associated with classic vulvar intraepithelial neoplasia (VIN). Keratinizing SCC is associated with lichen sclerosus and differentiated VIN, but not with human papillomavirus. This study was undertaken to examine the expression patterns of ProEx C in vulvar SCC and its precursors. We analyzed 22 cases with normal vulvar epidermis, 13 cases of lichen sclerosus, 14 cases of condylomas, 23 cases of high-grade classic VIN, 6 cases of differentiated VIN, 3 cases of verrucous carcinomas, 10 cases of keratinizing SCC, and 8 cases of basaloid and warty SCC. ProEx C targets minichromosome maintenance protein and topoisomerase II alpha protein which are overexpressed in the cell nucleus during aberrant S-phase induction. Marked confluent ProEx C expression is present in high-grade classic VIN with nuclear staining extending into the middle and upper layers of the epidermis. Condylomas show parabasal nuclear immunoreactivity associated with scattered ProEx C-positive nuclei in the more differentiated suprabasilar layers. Invasive SCC shows variable staining patterns. In contrast, ProEx C staining is essentially limited to the basal and parabasal layers in normal epidermis, lichen sclerosus, differentiated VIN, and verrucous carcinoma. Overall, ProEx C is a useful proliferation marker for high-grade VIN analogous to the staining patterns reported in high-grade cervical intraepithelial neoplasia.

Expression of hypoxia-inducible factor-1α, vascular endothelial growth factor and prolyl hydroxylase domain protein 2 in cutaneous squamous cell carcinoma and precursor lesions and their relationship with histological stages and clinical features.

PubMed

An, Xiangjie; Xu, Guangfen; Yang, Liu; Wang, Yuejue; Li, Yan; McHepange, Uwesu O; Shen, Guanxin; Tu, Yating; Tao, Juan

2014-01-01

The hypoxia-inducible factor-1 (HIF-1α) pathway is associated with tumor growth, angiogenesis and metastasis in various carcinomas. Little is known regarding the role of the HIF-1α signaling pathway in cutaneous squamous cell carcinoma (SCC). We investigated the expression of HIF-1α, vascular endothelial growth factor (VEGF) and the HIF negative regulator, prolyl hydroxylase domain protein 2 (PHD2), in cutaneous SCC, Bowen's disease, seborrheic keratosis (SK) and normal skin by immunohistochemistry and in situ hybridization. Additionally, we explored the relationships between these factors and the clinical and histological characteristics of each disease. Our study indicated that the expression of HIF-1α and VEGF was significantly higher (P < 0.05) in cutaneous SCC than in Bowen's disease, SK or normal skin. In contrast, PHD2 showed significantly higher expression in normal skin compared with SK, Bowen's disease and cutaneous SCC (P < 0.05). Grade II-IV cutaneous SCC had higher expression levels of nuclear HIF-1α and cytoplasm VEGF protein but less nuclear PHD2 protein than grade Ι cutaneous SCC (P < 0.05). Overexpression of HIF-1α and VEGF, as well as the decreased expression of PHD2, may play important roles in the development of cutaneous SCC. © 2013 Japanese Dermatological Association.

Comparing Immunohistologic and Demographic Variables of Head and Neck Squamous Cell Carcinoma

DTIC Science & Technology

2015-06-01

HPV 16 and 18 which have a well-established association with cervical cancers . However, HPV 16 accounts for the majority ofHPV...These cancers are now subdivided into HPV associated ( HPV - SCC) and non- HPV associated squamous cell (SCC) carcinomas. HPV -SCG is a distinct entity... cell carcinomas. Laryngoscope 2009; 119(8): 1542-1549. 13. Venuti A, Paolini F. HPV detection methods in head and neck cancer . Head Neck

SQUAMOUS CELL CARCINOMA IN TWO SNOW LEOPARDS (UNCIA UNCIA) WITH UNUSUAL AURICULAR PRESENTATION.

PubMed

Quintard, Benoît; Greunz, Eva Maria; Lefaux, Brice; Lemberger, Karin; Leclerc, Antoine

2017-06-01

Squamous cell carcinoma (SCC) is well documented in snow leopards ( Uncia uncia ) and most common locations are oral, facial, or pedal. These two cases illustrate an unusual auricular presentation, which is more often reported in white domestic cats. The animals were aged and presented clinical signs of otitis such as head shaking and ear scratching. Clinical examinations showed auricular canal masses with chronic purulent otitis. In both cases, clinical deterioration led to euthanasia and histology of the ear canal was consistent with SCC and showed numerous vascular emboli. These cases illustrate an unreported aggressive localization for SCC in snow leopards, which should be included in the differential diagnosis of otitis in this species. Auricular SCC may be underdiagnosed as the ear canal is infrequently sampled for histopathology. This auricular localization should be considered when metastases are found upon necropsy without internal primary tumor.

Neuroendocrine-type prostatic adenocarcinoma with microsatellite instability in a patient with lynch syndrome.

PubMed

Wagner, David G; Gatalica, Zoran; Lynch, Henry T; Kohl, Shane; Johansson, Sonny L; Lele, Subodh M

2010-12-01

Lynch syndrome is an autosomal-dominant cancer syndrome that can be identified with microsatellite instability molecular tests or immunohistochemical stains on pathologic material from patients who meet the Amsterdam Criteria II. The development of prostatic carcinoma in situ or invasive small cell carcinoma (SCC) of the prostate has not been previously reported in a patient with this syndrome. In this report, an 87-year-old White man with the Lynch syndrome had a prostate biopsy that revealed a mixed high-grade conventional adenocarcinoma and SCC of the prostate with high-grade prostatic intraepithelial neoplasia of the small cell neuroendocrine-type (HGPIN-NE), all showing MSH2 microsatellite instability and loss of MSH2 expression, a finding not previously published. These findings suggest that HGPIN-NE is a precursor of invasive SCC and also that prostatic SCC can develop in a patient with the Lynch syndrome.

Carcinomatous myelitis and meningitis after a squamous cell carcinoma of the lip.

PubMed

Pougnet, Isabelle; Murati, Anne; Sarran, Anthony; Viens, Patrice; Sabatier, Renaud

2014-01-01

Nervous central system metastases from head and neck squamous cell carcinoma (SCC) are rare. We report an exceptional case of isolated leptomeningeal and spinal cord involvement few years after the diagnosis of invasive SCC of the lip. A 33-year-old man with a history of infracentimetric carcinoma of the lip developed back pain associated with progressive neurological disorders leading to paraplegia. This atypical presentation led to initial misdiagnosis, but radiological and cytological explorations finally confirmed the diagnosis of leptomeningeal and intramedullar secondary spinal cord lesions from his previously treated head and neck SCC. Systemic targeted therapy with epidermal growth factor receptor inhibitor and intrathecal chemotherapy led to prolonged disease stabilization. To our knowledge, this is the first case of isolated neurological metastases from a head and neck SCC. Combination of systemic targeted therapy and intrathecal chemotherapy may be effective in such cases.

Differential diagnosis of well-differentiated squamous cell carcinoma from non-neoplastic oral mucosal lesions: New cytopathologic evaluation method dependent on keratinization-related parameters but not nuclear atypism.

PubMed

Hara, Hitoshi; Misawa, Tsuneo; Ishii, Eri; Nakagawa, Miki; Koshiishi, Saki; Amemiya, Kenji; Oyama, Toshio; Tominaga, Kazuya; Cheng, Jun; Tanaka, Akio; Saku, Takashi

2017-05-01

The cytology of oral squamous cell carcinoma (SCC) is challenging because oral SCC cells tend to be well differentiated and lack nuclear atypia, often resulting in a false negative diagnosis. The purpose of this study was to establish practical cytological parameters specific to oral SCCs. We reviewed 123 cases of malignancy and 53 of non-neoplastic lesions of the oral mucosa, which had been diagnosed using both cytology and histopathology specimens. From those, we selected 12 SCC and 4 CIS cases that had initially been categorized as NILM to ASC-H with the Bethesda system, as well as 4 non-neoplastic samples categorized as LSIL or ASC-H as controls, and compared their characteristic findings. After careful examinations, we highlighted five cytological parameters, as described in Results. Those 20 cytology samples were then reevaluated by 4 independent examiners using the Bethesda system as well as the 5 parameters. Five cytological features, (i) concentric arrangement of orangeophilic cells (indicating keratin pearls), (ii) large number of orangeophilic cells, (iii) bizarre-shaped orangeophilic cells without nuclear atypia, (iv) keratoglobules, and (v) uneven filamentous cytoplasm, were found to be significant parameters. All malignant cases contained at least one of those parameters, while none were observed in the four non-neoplastic cases with nuclear atypia. In reevaluations, the Bethesda system did not help the screeners distinguish oral SCCs from non-neoplastic lesions, while use of the five parameters enabled them to make a diagnosis of SCC. Recognition of the present five parameters is useful for oral SCC cytology. Diagn. Cytopathol. 2017;45:406-417. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

The Effects of Task, Database, and Guidance on Interaction in a Goal-Based Scenario.

ERIC Educational Resources Information Center

Bell, Benjamin

This paper describes the "Sickle Cell Counselor" (SCC), a goal based scenario on permanent display at the Museum of Science and Industry in Chicago. SCC is an exploratory hypermedia simulation program which provides users with a basic understanding of Sickle Cell Anemia. The user of the program plays the role of a genetic counselor, and,…

FRMD4A upregulation in human squamous cell carcinoma promotes tumor growth and metastasis and is associated with poor prognosis.

PubMed

Goldie, Stephen J; Mulder, Klaas W; Tan, David Wei-Min; Lyons, Scott K; Sims, Andrew H; Watt, Fiona M

2012-07-01

New therapeutic strategies are needed to improve treatment of head and neck squamous cell carcinoma (HNSCC), an aggressive tumor with poor survival rates. FRMD4A is a human epidermal stem cell marker implicated previously in epithelial polarity that is upregulated in SCC cells. Here, we report that FRMD4A upregulation occurs in primary human HNSCCs where high expression levels correlate with increased risks of relapse. FRMD4A silencing decreased growth and metastasis of human SCC xenografts in skin and tongue, reduced SCC proliferation and intercellular adhesion, and stimulated caspase-3 activity and expression of terminal differentiation markers. Notably, FRMD4A attenuation caused nuclear accumulation of YAP, suggesting a potential role for FRMD4A in Hippo signaling. Treatment with the HSP90 inhibitor 17-DMAG or ligation of CD44 with hyaluronan caused nuclear depletion of FRMD4A, nuclear accumulation of YAP and reduced SCC growth and metastasis. Together, our findings suggest FRMD4A as a novel candidate therapeutic target in HNSCC based on the key role in metastatic growth we have identified. ©2012 AACR.

Unusual recurrent tongue spindle cell carcinoma with marked anaplasia occurring at the site of glossectomy for a well-differentiated squamous cell carcinoma: A case report.

PubMed

Okuyama, Kohei; Fujita, Shuichi; Yanamoto, Souichi; Naruse, Tomofumi; Sakamoto, Yuki; Kawakita, Akiko; Omori, Keisuke; Tsuchihashi, Hiroki; Umeda, Masahiro

2017-09-01

Spindle cell carcinoma (SpCC), which predominantly arises in the oral, pharyngeal and laryngeal mucosal tissues, is composed of a mixture of squamous and sarcomatoid components. The present study describes the case of a 62-year-old woman with SpCC recurrence 4 years after an initial surgery to remove a well-differentiated primary squamous cell carcinoma (SCC) of the tongue. The recurrent tumor was spherical and located deep within the tongue tissue, which differs from the typical manifestation of ulcerated masses of the mucosa. The majority of cases of recurrence involving SpCC are associated with radiotherapeutic treatment of the primary malignancy; however, the patient in the present study had not received postoperative radiotherapy for SCC. Furthermore, the recurrent tumor in the present case exhibited marked anaplasia and sarcomatoid features, and the absence of SCC elements upon biopsy rendered histological diagnosis difficult. In summary, the present findings suggest that immunohistochemical examination and identification of SCC components are essential for ensuring the accuracy of the histological diagnosis of recurrent SpCC following a primary epithelial malignancy.

Unusual recurrent tongue spindle cell carcinoma with marked anaplasia occurring at the site of glossectomy for a well-differentiated squamous cell carcinoma: A case report

PubMed Central

Okuyama, Kohei; Fujita, Shuichi; Yanamoto, Souichi; Naruse, Tomofumi; Sakamoto, Yuki; Kawakita, Akiko; Omori, Keisuke; Tsuchihashi, Hiroki; Umeda, Masahiro

2017-01-01

Spindle cell carcinoma (SpCC), which predominantly arises in the oral, pharyngeal and laryngeal mucosal tissues, is composed of a mixture of squamous and sarcomatoid components. The present study describes the case of a 62-year-old woman with SpCC recurrence 4 years after an initial surgery to remove a well-differentiated primary squamous cell carcinoma (SCC) of the tongue. The recurrent tumor was spherical and located deep within the tongue tissue, which differs from the typical manifestation of ulcerated masses of the mucosa. The majority of cases of recurrence involving SpCC are associated with radiotherapeutic treatment of the primary malignancy; however, the patient in the present study had not received postoperative radiotherapy for SCC. Furthermore, the recurrent tumor in the present case exhibited marked anaplasia and sarcomatoid features, and the absence of SCC elements upon biopsy rendered histological diagnosis difficult. In summary, the present findings suggest that immunohistochemical examination and identification of SCC components are essential for ensuring the accuracy of the histological diagnosis of recurrent SpCC following a primary epithelial malignancy. PMID:28781811

The effect of somatic cell count data adjustment and interpretation, as outlined in European Union legislation, on herd eligibility to supply raw milk for processing of dairy products.

PubMed

More, S J; Clegg, T A; Lynch, P J; O'Grady, L

2013-06-01

Somatic cell count (SCC) limits are a key component of national and international regulation for milk quality. As yet, very limited work has been published on SCC regulatory standards, including on the effect of different approaches to SCC data adjustment and interpretation. This study examines the effect of SCC data adjustment and interpretation, as outlined in current European Union (EU) legislation, on herd eligibility to supply raw milk for processing of dairy products for human consumption, using Irish data for illustration. The study used Irish milk-recording data as a proxy for bulk tank SCC (BTSCC) data, to calculate an unadjusted monthly SCC value for each herd during each month of participation. Subsequently, 4 data adjustments were applied, as outlined in EU and national legislation: seasonal adjustment; 3-mo rolling geometric average, without accounting for a break in the supply; 3-mo rolling geometric average, after accounting for a break in the supply; and seasonal adjustment and 3-mo rolling geometric average combined, after accounting for a break in the supply. Analyses were conducted to examine the effect, during the period from 2004 to 2010, of data adjustment on the percentage of herds with herd SCC >400,000 cells/mL. In all, 4 interpretation scenarios, incorporating different data adjustment combinations, were used to estimate herd eligibility (compliant, under warning, or suspended, as defined by legislation) to supply raw milk for processing. The 4 methods of data adjustment each led to a sizable reduction (6.7, 5.0, 5.3, and 11.1 percentage points, respectively, compared with the unadjusted data) in the percentage of herds exceeding a herd SCC of 400,000 cells/mL. Herd eligibility varied by interpretation scenarios, in particular those incorporating seasonal adjustment. The study provides new perspectives on the effect of data adjustment on herd SCC and of interpretation scenarios on herd eligibility. The results provide an illustrative, rather than definitive, picture of this effect, as national authorities use BTSCC data when determining herd eligibility, whereas this study was conducted using milk-recording data as a proxy. Some aspects of the primary EU legislation are unclear, which may lead to differences in interpretation and application. The potential impact of data adjustment and milk purchaser pricing on farm-level mastitis control in Ireland is considered. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Meat and heme iron intake and risk of squamous cell carcinoma of the upper aero-digestive tract in the European Prospective Investigation into Cancer and Nutrition (EPIC)

PubMed Central

Steffen, Annika; Bergmann, Manuela M.; Sánchez, María-José; Chirlaque, Maria-Dolores; Jakszyn, Paula; Amiano, Pilar; Quirós, J. Ramón; Gurrea, Aurelio Barricarte; Ferrari, Pietro; Romieu, Isabelle; Fedirko, Veronika; Bueno-de-Mesquita, H. B(as).; Siersema, Peter D.; Peeters, Petra HM; Khaw, Kay-Tee; Wareham, Nick; Allen, Naomi E.; Crowe, Francesca L.; Skeie, Guri; Hallmanns, Göran; Johansson, Ingegerd; Borgquist, Signe; Ericson, Ulrika; Egeberg, Rikke; Tjønneland, Anne; Overvad, Kim; Grote, Verena; Li, Kuanrong; Trichopoulou, Antonia; Oikonomidou, Despoina; Pantzalis, Menelaos; Tumino, Rosario; Panico, Salvatore; Palli, Domenico; Krogh, Vittorio; Naccarati, Alessio; Mouw, Traci; Vergnaud, Anne-Claire; Norat, Teresa; Boeing, Heiner

2012-01-01

Background Evidence from prospective studies on intake of meat and fish and risk of squamous cell carcinoma (SCC) of the upper aero-digestive tract (UADT) is scarce. We prospectively investigated the association of meat and fish intake with risk of SCC of the UADT and the possible mechanism via heme iron in the large multi-center European Prospective Investigation into Cancer and Nutrition (EPIC) study. Methods Multivariable proportional hazards models were used to estimate relative risks of SCC of the UADT in relation to intake of total meat, as well as subtypes of meat, fish and heme iron among 348,738 individuals from 7 European countries. Results During an average follow-up of 11.8 years, a total of 682 incident cases of UADT SCC were accrued. Intake of processed meat was positively associated with risk of SCC of the UADT in the total cohort (highest versus lowest quintile: RR=1.41; 95% CI=1.03-1.94), however, in stratified analyses, this association was confined to the group of current smokers (highest versus lowest quintile: RR=1.89; 95% CI=1.22-2.93). Red meat, poultry, fish and heme iron were not consistently related to UADT SCC. Conclusion Higher intake of processed meat was positively associated with SCC of the UADT among smokers. Although this finding was stable in various sensitivity analyses, we cannot rule out residual confounding by smoking. Confirmation in future studies and identification of biological mechanisms is warranted. Impact Smokers may further increase their risk for SCC of the UADT if they additionally consume large amounts of processed meat. PMID:23033453

Heterogeneous relationships of squamous and basal cell carcinomas of the skin with smoking: the UK Million Women Study and meta-analysis of prospective studies.

PubMed

Pirie, Kirstin; Beral, Valerie; Heath, Alicia K; Green, Jane; Reeves, Gillian K; Peto, Richard; McBride, Penelope; Olsen, Catherine M; Green, Adèle C

2018-06-14

Published findings on the associations between smoking and the incidence of cutaneous squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) are inconsistent. We aimed to generate prospective evidence on these relationships overall and by anatomical site. We followed 1,223,626 women without prior cancer by electronic linkage to national cancer registration data. Questionnaire information about smoking and other factors was recorded at recruitment (1996-2001) and every 3-5 years subsequently. Cox regression yielded adjusted relative risks (RRs) comparing smokers versus never-smokers. After 14 (SD4) years follow-up per woman, 6699 had a first registered cutaneous SCC and 48,666 a first BCC. In current versus never-smokers, SCC incidence was increased (RR = 1.22, 95% CI 1.15-1.31) but BCC incidence was decreased (RR = 0.80, 0.78-0.82). RRs varied substantially by anatomical site; for the limbs, current smoking was associated with an increased incidence of SCC (1.55, 1.41-1.71) and a decreased incidence of BCC (0.72, 0.66-0.79), but for facial lesions there was little association of current smoking with either SCC (0.93, 0.82-1.06) or BCC (0.92, 0.88-0.96). Findings in meta-analyses of results from this and seven other prospective studies were largely dominated by the findings in this study. Smoking-associated risks for cutaneous SCC and BCC are in the opposite direction to each other and appear to vary by anatomical site.

Epithelial expression of extracellular matrix metalloproteinase inducer/CD147 and matrix metalloproteinase-2 in neoplasms and precursor lesions derived from cutaneous squamous cells: An immunohistochemical study.

PubMed

Ayva, Sebnem Kupana; Karabulut, Ayse Anil; Akatli, Ayşe Nur; Atasoy, Pinar; Bozdogan, Onder

2013-10-01

Extracellular matrix metalloproteinase inducer (CD147) is a transmembrane glycoprotein involved in the regulation of matrix metalloproteinases (MMPs). The study investigated CD147 and MMP-2 expression in epidermis of cutaneous squamous lesions. CD147 and MMP-2 expressions were evaluated immunohistochemically in 44 specimens: 18 actinic keratoses (AK), 6 squamous cell carcinomas in situ (SCCIS), 13 squamous cell carcinomas (SCC; peritumoral and invasive portions assessed), and 7 normal skins. Patterns of expression were assessed, with MMP-2 in nuclei (MMP-2n) and cytoplasm (MMP-2c) evaluated separately. The expression of each marker was quantified using a calculated immunohistochemical/histologic score (H-score). Correlations were analyzed for the marker H-scores in each study group. Associations between H-scores and histopathologic parameters were also evaluated. CD147 H-score was the highest in SCC (invasive islands), followed by AK, SCCIS, and control specimens, respectively. MMP-2n and MMP-2c H-scores were the highest in AK, followed by SCCIS, SCC, and control specimens, respectively. MMP-2c and MMP-2n H-scores were significantly higher in peritumoral epidermis than in invasive islands of SCC. MMP-2c and CD147 H-scores were positively correlated in the peritumoral SCCs. CD147 H-score was positively correlated with tumor differentiation in SCC. The findings suggest that overexpression of CD147 plays a role in the development of SCC. Copyright © 2013 Elsevier GmbH. All rights reserved.

Regulation of prohibitin expression during follicular development and atresia in the mammalian ovary.

PubMed

Thompson, Winston E; Asselin, Eric; Branch, Alicia; Stiles, Jonathan K; Sutovsky, Peter; Lai, Liangxue; Im, Gi-Sun; Prather, Randall S; Isom, S Clay; Rucker, Edmund; Tsang, Benjamin K

2004-07-01

Prohibitin is a ubiquitous and highly conserved protein implicated as an important regulator in cell survival. Prohibitin content is inversely associated with cell proliferation, but it increases during granulosa cell differentiation as well as in earlier events of apoptosis in a temperature-sensitive granulosa cell line. In the present study, we have characterized the spatial expression patterns for prohibitin using established in vivo models for the induction of follicular development and atresia in the mammalian ovary. Comparative Western blot analyses of granulosa cell lysates from control ovaries and from ovaries primed with eCG or treated with eCG plus anti-eCG (gonadotropin withdrawal) were conducted. Prohibitin was immunolocalized in rat ovarian sections probed with antibodies against either proliferating cell nuclear antigen (PCNA) or cholesterol side-chain cleavage cytochrome P450 (P450(scc)) or in terminal deoxynucleotidyl transferase-mediated dUTP nick end labeled sections. Additionally, porcine oocytes, zygotes, and blastocyts were also immunolocalized with prohibitin antibody. Immunolocalization revealed the presence of prohibitin in granulosa cells, theca-interstitial cells, and the oocyte. The results indicate that prohibitin protein expression in the gonadotropin-treated cells was upregulated. Immunoreactivity of prohibitin was inversely related to PCNA expression during follicular maturation and colocalized with P450(scc). Prohibitin appeared to be translocated from the cytoplasm to the nucleus in atretic follicles, germinal vesicle-stage oocytes, zygotes, and blastocysts. These results suggest that prohibitin has several functional regulatory roles in granulosa and theca-interstitial cells and in the ovum during follicular maturation and atresia. It is likely that prohibitin may play an important role in determining the fate of these cells and eventual follicular destiny.

[Analysis of tissue-specific differentially methylated genes with differential gene expression in non-small cell lung cancer].

PubMed

Yin, L G; Zou, Z Q; Zhao, H Y; Zhang, C L; Shen, J G; Qi, L; Qi, M; Xue, Z Q

2014-01-01

Adenocarcinoma (ADC) and squamous cell carcinomas (SCC) are two subtypes of non-small cell lung carcinomas which are regarded as the leading cause of cancer-related malignancy worldwide. The aim of this study is to detect the differentially methylated loci (DMLs) and differentially methylated genes (DMGs) of these two tumor sets, and then to illustrate the different expression level of specific methylated genes. Using TCGA database and Illumina HumanMethylation 27 arrays, we first screened the DMGs and DMLs in tumor samples. Then, we explored the BiologicalProcess terms of hypermethylated and hypomethylated genes using Functional Gene Ontology (GO) catalogues. Hypermethylation intensively occurred in CpG-island, whereas hypomethylation was located in non-CpG-island. Most SCC and ADC hypermethylated genes involved GO function of DNA dependenit regulation of transcription, and hypomethylated genes mainly 'enriched in the term of immune responses. Additionally, the expression level of specific differentially methylated genesis distinctbetween ADC and SCC. It is concluded that ADC and SCC have different methylated status that might play an important role in carcinogenesis.

Oligodendrocyte precursor cell transplantation promotes functional recovery following contusive spinal cord injury in rats and is associated with altered microRNA expression

PubMed Central

Yang, Jin; Xiong, Liu-Lin; Wang, You-Cui; He, Xiang; Jiang, Ling; Fu, Song-Jun; Han, Xue-Fei; Liu, Jia; Wang, Ting-Hua

2018-01-01

It has been reported that oligodendrocyte precursor cells (OPCs) may be used to treat contusive spinal cord injury (SCC), and may alter microRNA (miRNA/miR) expression following SCC in rats. However, the association between miRNA expression and the treatment of rats with SCC with OPC transplantation remain unclear. The present study transplanted OPCs into the spinal cord of rats with SCC and subsequently used the Basso, Beattie and Bresnahan (BBB) score to assess the functional recovery and pain scores. An miRNA assay was performed to detect differentially expressed miRNAs in the spinal cord of SCC rats transplanted with OPCs, compared with SCC rats transplanted with medium. Quantitative polymerase chain reaction was used to verify significantly altered miRNA expression levels. The results demonstrated that OPC transplantation was able to improve motor recovery and relieve mechanical allodynia in rats with SCC. In addition, through a miRNA assay, 45 differentially expressed miRNAs (40 upregulated miRNAs and 5 downregulated miRNAs) were detected in the spinal cord of rats in the OPC group compared with in the Medium group. Differentially expressed miRNAs were identified according to the following criteria: Fold change >2 and P<0.05. Furthermore, quantitative polymerase chain reaction was used to verify the most highly upregulated (miR-375-3p and miR-1-3p) and downregulated (miR-363-3p, miR-449a-5p and miR-3074) spinal cord miRNAs that were identified in the miRNA assay. In addition, a bioinformatics analysis of these miRNAs indicated that miR-375 and miR-1 may act primarily to inhibit cell proliferation and apoptosis via transcriptional and translational regulation, whereas miR-363, miR-449a and miR-3074 may act primarily to inhibit cell proliferation and neuronal differentiation through transcriptional regulation. These results suggested that OPC transplantation may promote functional recovery of rats with SCC, which may be associated with the expression of various miRNAs in the spinal cord, including miR-375-3p, miR-1-3p, miR-363-3p, miR-449a-5p and miR-3074. PMID:29115639

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vaid, Mudit; Prasad, Ram; Singh, Tripti

Grape seed proanthocyanidins (GSPs) have been shown to have anti-skin carcinogenic effects in in vitro and in vivo models. However, the precise epigenetic molecular mechanisms remain unexplored. This study was designed to investigate whether GSPs reactivate silenced tumor suppressor genes following epigenetic modifications in skin cancer cells. For this purpose, A431 and SCC13 human squamous cell carcinoma cell lines were used as in vitro models. The effects of GSPs on DNA methylation, histone modifications and tumor suppressor gene expressions were studied in these cell lines using enzyme activity assays, western blotting, dot-blot analysis and real-time polymerase chain reaction (RT-PCR). Wemore » found that treatment of A431 and SCC13 cells with GSPs decreased the levels of: (i) global DNA methylation, (ii) 5-methylcytosine, (iii) DNA methyltransferase (DNMT) activity and (iv) messenger RNA (mRNA) and protein levels of DNMT1, DNMT3a and DNMT3b in these cells. Similar effects were noted when these cancer cells were treated identically with 5-aza-2′-deoxycytidine, an inhibitor of DNA methylation. GSPs decreased histone deacetylase activity, increased levels of acetylated lysines 9 and 14 on histone H3 (H3-Lys 9 and 14) and acetylated lysines 5, 12 and 16 on histone H4, and reduced the levels of methylated H3-Lys 9. Further, GSP treatment resulted in re-expression of the mRNA and proteins of silenced tumor suppressor genes, RASSF1A, p16{sup INK4a} and Cip1/p21. Together, this study provides a new insight into the epigenetic mechanisms of GSPs and may have significant implications for epigenetic therapy in the treatment/prevention of skin cancers in humans. -- Highlights: ►Epigenetic modulations have been shown to have a role in cancer risk. ►Proanthocyanidins decrease the levels of DNA methylation and histone deacetylation. ►Proanthocyanidins inhibit histone deacetylase activity in skin cancer cells. ►Proanthocyanidins reactivate tumor suppressor genes in skin cancer cells. ►Grape seed proanthocyanidins can prevent skin cancer through epigenetic modulation.« less

The effect of estrus synchronization treatments on somatic cell count of transitional-anestrus Awassi ewes' milk.

PubMed

Talafha, A Q; Lafi, S Q; Ababneh, M M

2009-02-01

Fifty-three transitional-anestrus Awassi ewes, randomly assigned to three groups: fluorogestone acetate (FGA, n = 18), FGA-Prostaglandin (FGA-PGF, n = 18) and control (n = 17), were used to examine the effect of estrus synchronization protocols and steroid hormones concentrations on milk somatic cell count (SCC). Intravaginal FGA sponge was inserted for 13 days and 600 IU equine chorionic gonadotropin was administered for ewes of FGA and FGA-PGF groups at the time of sponge removal (day 0). In addition, 10 mg was administered to ewes of FGA-PGF group on day 0. Blood and milk samples were collected from all ewes on days -13, -6, 0, 1, 2, 7 and 14. Estradiol had significant positive correlation with the SCC during the periods of sponge insertion (P = 0.015, r = 0.235) and within two days (P = 0.063 r = 0.23) after sponge removal with no correlation with SCC of both udder halves during the luteal phase. Progesterone concentrations, on the other hand, had a significant positive correlation (P < 0.001; r = 0.420) with the SCC of both udder halves during the luteal phase of the experiment, but not during the periods of sponge insertion and expected estrus. SCC returned under the influence of endogenous progesterone on days 7 and 14 to pre-synchronization values. In conclusion, sheep milk SCC is affected significantly with induction of estrus and steroid hormones concentrations. However, peak SCC recorded during estrus was far below the upper limit of the current standard for normal milk. With the current standards for SCC of 1,000,000/ml as legal limit for abnormal milk control programs in sheep, estrus synchronization programs and the estrus status should not be considered when bulk-tank milk SCC is being investigated, but should be considered during the process of setting new standards.

Histogram analysis of apparent diffusion coefficient maps for the differentiation between lymphoma and metastatic lymph nodes of squamous cell carcinoma in head and neck region.

PubMed

Wang, Yan-Jun; Xu, Xiao-Quan; Hu, Hao; Su, Guo-Yi; Shen, Jie; Shi, Hai-Bin; Wu, Fei-Yun

2018-06-01

Background To clarify the nature of cervical malignant lymphadenopathy is highly important for the diagnosis and differential diagnosis of head and neck tumors. Purpose To investigate the role of first-order apparent diffusion coefficient (ADC) histogram analysis for differentiating lymphoma from metastatic lymph nodes of squamous cell carcinoma (SCC) in the head and neck region. Material and Methods Diffusion-weighted imaging (DWI) data of 67 patients (lymphoma, n = 20; SCC, n = 47) with malignant lymphadenopathy were retrospectively analyzed. The SCC group was divided into nasopharyngeal SCC and non-nasopharyngeal SCC groups. The ADC histogram features (ADC 10 , ADC 25 , ADC mean , ADC median , ADC 75 , ADC 90 , skewness, and kurtosis) were derived and then compared by independent-samples t-test and one-way analysis of variance test, respectively. Receiver operating characteristic curve analyses were employed to investigate diagnostic performance of the significant parameters. Results Lymphoma showed significantly lower ADC mean , ADC median , ADC 75 , and ADC 90 than SCC (all P < 0.05). Setting ADC 90  = 0.719 × 10 -3  mm 2 /s as the threshold value, optimal diagnostic performance was achieved (area under the curve [AUC] = 0.719, sensitivity = 95.7%, specificity = 50.0%). Subgroup analyses showed no significant difference between lymphoma and NPC (all P > 0.05). Lymphoma showed significantly lower ADC 25 , ADC mean , ADC median , ADC 75 , and ADC 90 than non-nasopharyngeal SCC (all P < 0.05). Optimal diagnostic performance (AUC = 0.847, sensitivity = 86.7%, specificity = 80.0%) could be achieved when setting ADC 90  = 0.943 × 10 -3  mm 2 /s as the threshold value. Conclusion Given its limitations, our study has shown that first-order ADC histogram analysis is capable of differentiating lymphoma from metastatic lymph nodes of SCC, especially those of non-nasopharyngeal SCC.

Green tea polyphenol, (-)-epigallocatechin-3-gallate, induces toxicity in human skin cancer cells by targeting β-catenin signaling.

PubMed

Singh, Tripti; Katiyar, Santosh K

2013-12-01

The green tea polyphenol, (-)-epigallocatechin-3-gallate (EGCG), has been shown to have anti-carcinogenic effects in several skin tumor models, and efforts are continued to investigate the molecular targets responsible for its cytotoxic effects to cancer cells. Our recent observation that β-catenin is upregulated in skin tumors suggested the possibility that the anti-skin carcinogenic effects of EGCG are mediated, at least in part, through its effects on β-catenin signaling. We have found that treatment of the A431 and SCC13 human skin cancer cell lines with EGCG resulted in reduced cell viability and increased cell death and that these cytotoxic effects were associated with inactivation of β-catenin signaling. Evidence of EGCG-induced inactivation of β-catenin included: (i) reduced accumulation of nuclear β-catenin; (ii) enhanced levels of casein kinase1α, reduced phosphorylation of glycogen synthase kinase-3β, and increased phosphorylation of β-catenin on critical serine(45,33/37) residues; and (iii) reduced levels of matrix metalloproteinase (MMP)-2 and MMP-9, which are down-stream targets of β-catenin. Treatment of cells with prostaglandin E2 (PGE2) enhanced the accumulation of β-catenin and enhanced β-catenin signaling. Treatment with either EGCG or an EP2 antagonist (AH6809) reduced the PGE2-enhanced levels of cAMP, an upstream regulator of β-catenin. Inactivation of β-catenin by EGCG resulted in suppression of cell survival signaling proteins. siRNA knockdown of β-catenin in A431 and SCC13 cells reduced cell viability. Collectively, these data suggest that induction of cytotoxicity in skin cancer cells by EGCG is mediated by targeting of β-catenin signaling and that the β-catenin signaling is upregulated by inflammatory mediators. © 2013.

Comparison of cephalonium alone and in combination with an internal teat sealant for dry cow therapy in seasonally calving dairy cows.

PubMed

Bates, A J; Chambers, G; Laven, R A

2016-03-01

To assess the effect of combining an internal teat sealant (ITS) and a long-acting cephalonium-based dry cow therapy (DCT) on the prevalence of cows with a somatic cell count (SCC) >150,000 cells/mL 60-80 days after calving, and the incidence of clinical mastitis diagnosed by farm staff in the first 100 days after calving. Cows from a spring-calving, pasture-based, dairy farm in the South Canterbury region of New Zealand were randomly allocated to receive cephalonium DCT (n=289) or cephalonium and internal teat sealant (n=304) at the end of lactation. Cows were inspected twice daily by farm staff during the dry period and following calving for signs of mastitis. Individual SCC were determined from herd tests conducted in the previous lactation and following calving. Logistic regression models were used to determine relationships with the prevalence of cows with a SCC >150,000 cells/mL after calving, and survival analysis was used to model time to the first case of clinical mastitis following calving at the cow and quarter level. The OR for a cow with a SCC >150,000 cells/mL after calving, including age and individual SCC in the preceding lactation in the model, was 0.53 (95% CI=0.32-0.89) for cows treated with combination therapy compared to cows receiving cephalonium (p=0.017). At the cow level, including age and preceding SCC in the model, the hazard ratio for diagnosis of clinical mastitis by farm staff in the first 100 days of lactation was 0.60 (95% CI=0.39-0.98) for cows treated with combination therapy compared to cows receiving cephalonium (p=0.04). At the quarter level, the hazard ratio for diagnosis of clinical mastitis, with age included in the model, was 0.41 (95% CI=0.23-0.74) for the combination therapy compared to cephalonium alone (p<0.001). The combination of internal teat sealant and cephalonium DCT was more effective than cephalonium alone at reducing clinical mastitis diagnosed by farm staff in the 100 days after calving, and the prevalence of cows with a SCC >150,000 cells/mL 60-80 days after calving. This study adds to the evidence that the prevention of intra mammary infections throughout the dry period and up to calving by using combination therapy is important in reducing the incidence of farmer-diagnosed clinical mastitis and prevalence of cows with a SCC >150,000 cells/mL 60-80 days after calving.

MHI-148 Cyanine Dye Conjugated Chitosan Nanomicelle with NIR Light-Trigger Release Property as Cancer Targeting Theranostic Agent.

PubMed

Thomas, Reju George; Moon, Myeong Ju; Surendran, Suchithra Poilil; Park, Hyeong Ju; Park, In-Kyu; Lee, Byeong-Il; Jeong, Yong Yeon

2018-02-15

Paclitaxel (PTX) loaded hydrophobically modified glycol chitosan (HGC) micelle is biocompatible in nature, but it requires cancer targeting ability and stimuli release property for better efficiency. To improve tumor retention and drug release characteristic of HGC-PTX nanomicelles, we conjugated cancer targeting heptamethine dye, MHI-148, which acts as an optical imaging agent, targeting moiety and also trigger on-demand drug release on application of NIR 808 nm laser. The amine group of glycol chitosan modified with hydrophobic 5β-cholanic acid and the carboxyl group of MHI-148 were bonded by 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide/N-hydroxysuccinimide chemistry. Paclitaxel was loaded to MHI-HGC nanomicelle by an oil-in-water emulsion method, thereby forming MHI-HGC-PTX. Comparison of near infrared (NIR) dyes, MHI-148, and Flamma-774 conjugated to HGC showed higher accumulation for MHI-HGC in 4T1 tumor and 4T1 tumor spheroid. In vitro studies showed high accumulation of MHI-HGC-PTX in 4T1 and SCC7 cancer cell lines compared to NIH3T3 cell line. In vivo fluorescence imaging of the 4T1 and SCC7 tumor showed peak accumulation of MHI-HGC-PTX at day 1 and elimination from the body at day 6. MHI-HGC-PTX showed good photothermal heating ability (50.3 °C), even at a low concentration of 33 μg/ml in 1 W/cm 2 808 nm laser at 1 min time point. Tumor reduction studies in BALB/c nude mice with SCC7 tumor showed marked reduction in MHI-HGC-PTX in the PTT group combined with photothermal therapy compared to MHI-HGC-PTX in the group without PTT. MHI-HGC-PTX is a cancer theranostic agent with cancer targeting and optical imaging capability. Our studies also showed that it has cancer targeting property independent of tumor type and tumor reduction property by combined photothermal and chemotherapeutic effects.

Height, height-related SNPs, and risk of non-melanoma skin cancer

PubMed Central

Li, Xin; Liang, Liming; Feng, Yen-Chen Anne; De Vivo, Immaculata; Giovannucci, Edward; Tang, Jean Y; Han, Jiali

2017-01-01

Background: Adult height has been associated with risk of several site-specific cancers, including melanoma. However, less attention has been given to non-melanoma skin cancer (NMSC). Methods: We prospectively examined the risk of squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) in relation to adult height in the Nurses' Health Study (NHS, n=117 863) and the Health Professionals Follow-up Study (HPFS, n=51 111). We also investigated the relationships between height-related genetic markers and risk of BCC and SCC in the genetic data sets of the NHS and HPFS (3898 BCC cases, and 8530 BCC controls; 527 SCC cases, and 8962 SCC controls). Results: After controlling for potential confounding factors, the hazard ratios were 1.09 (95% CI: 1.02, 1.15) and 1.10 (95% CI: 1.07, 1.13) for the associations between every 10 cm increase in height and risk of SCC and BCC respectively. None of the 687 height-related single-nucleotide polymorphisms (SNPs) was significantly associated with the risk of SCC or BCC, nor were the genetic scores combining independent height-related loci. Conclusions: Our data from two large cohorts provide further evidence that height is associated with an increased risk of NMSC. More studies on height-related genetic loci and early-life exposures may help clarify the underlying mechanisms. PMID:27846199

Risk factors for development of primary bladder squamous cell carcinoma

PubMed Central

Hubbard, R; Swallow, D; Finch, W; Wood, SJ; Biers, SM

2017-01-01

INTRODUCTION The aim of this study was to investigate the prevalence of risk factors for primary squamous cell carcinoma (SCC) of the bladder. MATERIALS A total of 90 cases of primary SCC of the bladder were identified through multicentre analysis. Patient demographics, stage and grade of cancer at presentation, management and outcomes were recorded. The presence of known risk factors (catheter use, neuropathic bladder, smoking history, recurrent urinary tract infection and bladder stones) was also documented. RESULTS Over half of the patients had at least one identifiable risk factor for the development of primary bladder SCC: 13.9% of patients had a history of catheter use (clean intermittent self-catheterisation [CISC] in 11.1%), 10.0% of patients had a neuropathic bladder, 27.8% were smokers or ex-smokers and 20.0% had a documented history of recurrent urinary tract infection. Statistical analysis of the results showed no association between risk factors and grade of tumour at presentation. CONCLUSIONS These data further support the association between primary bladder SCC and several of the well documented risk factors for its development. Chronic use of CISC may confer a greater risk for development of SCC than thought previously. Further evidence of the role of CISC in primary SCC is required to justify routine screening and to determine exactly when surveillance of the bladder should begin for this group of patients. PMID:27869492

Erwinia carotovora elicitors and Botrytis cinerea activate defense responses in Physcomitrella patens

PubMed Central

Ponce de León, Inés; Oliver, Juan Pablo; Castro, Alexandra; Gaggero, Carina; Bentancor, Marcel; Vidal, Sabina

2007-01-01

Background Vascular plants respond to pathogens by activating a diverse array of defense mechanisms. Studies with these plants have provided a wealth of information on pathogen recognition, signal transduction and the activation of defense responses. However, very little is known about the infection and defense responses of the bryophyte, Physcomitrella patens, to well-studied phytopathogens. The purpose of this study was to determine: i) whether two representative broad host range pathogens, Erwinia carotovora ssp. carotovora (E.c. carotovora) and Botrytis cinerea (B. cinerea), could infect Physcomitrella, and ii) whether B. cinerea, elicitors of a harpin (HrpN) producing E.c. carotovora strain (SCC1) or a HrpN-negative strain (SCC3193), could cause disease symptoms and induce defense responses in Physcomitrella. Results B. cinerea and E.c. carotovora were found to readily infect Physcomitrella gametophytic tissues and cause disease symptoms. Treatments with B. cinerea spores or cell-free culture filtrates from E.c. carotovoraSCC1 (CF(SCC1)), resulted in disease development with severe maceration of Physcomitrella tissues, while CF(SCC3193) produced only mild maceration. Although increased cell death was observed with either the CFs or B. cinerea, the occurrence of cytoplasmic shrinkage was only visible in Evans blue stained protonemal cells treated with CF(SCC1) or inoculated with B. cinerea. Most cells showing cytoplasmic shrinkage accumulated autofluorescent compounds and brown chloroplasts were evident in a high proportion of these cells. CF treatments and B. cinerea inoculation induced the expression of the defense-related genes: PR-1, PAL, CHS and LOX. Conclusion B. cinerea and E.c. carotovora elicitors induce a defense response in Physcomitrella, as evidenced by enhanced expression of conserved plant defense-related genes. Since cytoplasmic shrinkage is the most common morphological change observed in plant PCD, and that harpins and B. cinerea induce this type of cell death in vascular plants, our results suggest that E.c. carotovora CFSCC1 containing HrpN and B. cinerea could also induce this type of cell death in Physcomitrella. Our studies thus establish Physcomitrella as an experimental host for investigation of plant-pathogen interactions and B. cinerea and elicitors of E.c. carotovora as promising tools for understanding the mechanisms involved in defense responses and in pathogen-mediated cell death in this simple land plant. PMID:17922917

A Population-based Case–Control Study of Urinary Arsenic Species and Squamous Cell Carcinoma in New Hampshire, USA

PubMed Central

Li, Zhigang; Perry, Ann E.; Spencer, Steven K.; Gandolfi, A. Jay; Karagas, Margaret R.

2013-01-01

Background: Chronic high arsenic exposure is associated with squamous cell carcinoma (SCC) of the skin, and inorganic arsenic (iAs) metabolites may play an important role in this association. However, little is known about the carcinogenicity of arsenic at levels commonly observed in the United States. Objective: We estimated associations between total urinary arsenic and arsenic species and SCC in a U.S. population. Methods: We conducted a population-based case–control SCC study (470 cases, 447 controls) in a U.S. region with moderate arsenic exposure through private well water and diet. We measured urinary iAs, monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA), and summed these arsenic species (ΣAs). Because seafood contains arsenolipids and arsenosugars that metabolize into DMA through alternate pathways, participants who reported seafood consumption within 2 days before urine collection were excluded from the analyses. Results: In adjusted logistic regression analyses (323 cases, 319 controls), the SCC odds ratio (OR) was 1.37 for each ln-transformed microgram per liter increase in ln-transformed ΣAs concentration [ln(ΣAs)] (95% CI: 1.04, 1.80). Urinary ln(MMA) and ln(DMA) also were positively associated with SCC (OR = 1.34; 95% CI: 1.04, 1.71 and OR = 1.34; 95% CI: 1.03, 1.74, respectively). A similar trend was observed for ln(iAs) (OR = 1.20; 95% CI: 0.97, 1.49). Percent iAs, MMA, and DMA were not associated with SCC. Conclusions: These results suggest that arsenic exposure at levels common in the United States relates to SCC and that arsenic metabolism ability does not modify the association. Citation: Gilbert-Diamond D, Li Z, Perry AE, Spencer SK, Gandolfi AJ, Karagas MR. 2013. A population-based case–control study of urinary arsenic species and squamous cell carcinoma in New Hampshire, USA. Environ Health Perspect 121:1154–1160; http://dx.doi.org/10.1289/ehp.1206178 PMID:23872349

Environmental and lifestyle risk factors for oral squamous cell carcinoma in domestic cats.

PubMed

Bertone, Elizabeth R; Snyder, Laura A; Moore, Antony S

2003-01-01

Oral squamous cell carcinoma (SCC) is a common malignancy in cats, but little currently is known about its etiology. We examined the relationship between risk of oral SCC and factors such as environmental tobacco smoke, flea control products, and diet in 36 domestic cats with histologically confirmed oral SCC and 112 renal disease control cats presented to a large veterinary referral hospital between 1994 and 2000. Questionnaires were mailed to owners of all study and control cats to assess demographic characteristics, lifestyle factors, and level of chemical exposures 2 years before diagnosis. Multivariate relative risks (RR) were used to estimate the relationships between the various factors and the risk of oral SCC. Flea control product use and diet were significantly associated with risk of oral SCC. Cats that wore a flea collar had 5 times the risk of oral SCC as nonusers, after adjustment for other factors (RR = 5.3; P = .002). In contrast, use of flea shampoo substantially reduced risk. Compared to cats eating mostly dry food, those with high canned food intake had a 3-fold increase in risk (RR = 3.6; P = .014); canned tuna fish intake was independently associated with risk (RR = 4.7; P = .004). Exposure to household environmental tobacco smoke was associated with a nonsignificant 2-fold increase in risk (P = .11). Results of this study suggest that flea control products, diet, and perhaps environmental tobacco smoke might be associated with risk of oral SCC and indicate that further investigation into these relationships is warranted.

Piroxicam and doxycycline treatment for an oral squamous cell carcinoma in an inshore bottlenose dolphin (Tursiops aduncus).

PubMed

March, D T; Blyde, D J; Bossart, G D; Begg, A P; Taylor, D P; McClure, V

2016-06-01

The virus family Papillomaviridae has been documented in a wide range of animal species and can cause benign and malignant proliferative lesions. The presence of concurrent lingual papillomas and squamous cell carcinomas (SCC) in cetaceans has also been documented in both wild and captive populations, suggesting malignant transformation of benign papilloma to SCC may occur in this species. In 2008, a 38-year-old captive male inshore bottlenose dolphin (Tursiops aduncus) was diagnosed with papillomatous lesions on the intermandibular frenulum rostral to the tongue and an infiltrative SCC of the soft palate following biopsy and histological analysis. A treatment regimen of piroxicam and doxycycline was initiated with misoprostol as a gastroprotectant. The treatment resulted in a marked reduction in tumour size and reversible hepatotoxicosis. Subsequent biopsies revealed the presence of SCC in the oral cavity; however, the disease remains stable at the time of writing. To the best of our knowledge, this case is the first report of piroxicam and doxycycline used to treat SCC in a bottlenose dolphin. The treatment was successful in reducing the clinical presentation of the disease. © 2016 Australian Veterinary Association.

Correlation between cell cycle proteins and hMSH2 in actinic cheilitis and lip cancer.

PubMed

Lopes, Maria Luiza Diniz de Sousa; de Oliveira, Denise Hélen Imaculada Pereira; Sarmento, Dmitry José de Santana; Queiroz, Lélia Maria Guedes; Miguel, Márcia Cristina da Costa; da Silveira, Éricka Janine Dantas

2016-04-01

This study aims to evaluate and verify the relationship between the immunoexpression of hMSH2, p53 and p21 in actinic cheilitis (AC) and lower lip squamous cell carcinoma (SCC) cases. Forty AC and 40 SCC cases were submitted to immunoperoxidase method and quantitatively analyzed. Expression was compared by Mann-Whitney test, Student t test or one-way ANOVA. To correlate the variables, Pearson's correlation coefficient was calculated. The expression of p53 and p21 showed no significant differences between histopathological grades of AC or lower lip SCC (p > 0.05). Immunoexpression of p53 was higher in SCC than in AC (p < 0.001), while p21 expression was more observed in AC when compared to SCC group (p = 0.006). The AC group revealed an inverse correlation between p53 and hMSH2 expression (r = -0.30, p = 0.006). Alterations in p53 and p21 expression suggest that these proteins are involved in lower lip carcinogenesis. Moreover, p53 and hMSH2 seem to be interrelated in early events of this process.

Vemurafenib cooperates with HPV to promote initiation of cutaneous tumors.

PubMed

Holderfield, Matthew; Lorenzana, Edward; Weisburd, Ben; Lomovasky, Lisa; Boussemart, Lise; Lacroix, Ludovic; Tomasic, Gorana; Favre, Michel; Vagner, Stephan; Robert, Caroline; Ghoddusi, Majid; Daniel, Dylan; Pryer, Nancy; McCormick, Frank; Stuart, Darrin

2014-04-15

Treatment with RAF inhibitors such as vemurafenib causes the development of cutaneous squamous cell carcinomas (cSCC) or keratoacanthomas as a side effect in 18% to 30% of patients. It is known that RAF inhibitors activate the mitogen-activated protein kinase (MAPK) pathway and stimulate growth of RAS-mutated cells, possibly accounting for up to 60% of cSCC or keratoacanthoma lesions with RAS mutations, but other contributing events are obscure. To identify such events, we evaluated tumors from patients treated with vemurafenib for the presence of human papilloma virus (HPV) DNA and identified 13% to be positive. Using a transgenic murine model of HPV-driven cSCC (K14-HPV16 mice), we conducted a functional test to determine whether administration of RAF inhibitors could promote cSCC in HPV-infected tissues. Vemurafenib treatment elevated MAPK markers and increased cSCC incidence from 22% to 70% in this model. Furthermore, 55% of the cSCCs arising in vemurafenib-treated mice exhibited a wild-type Ras genotype, consistent with the frequency observed in human patients. Our results argue that HPV cooperates with vemurafenib to promote tumorigenesis, in either the presence or absence of RAS mutations. ©2014 AACR.

Quercetin decrease somatic cells count in mastitis of dairy cows.

PubMed

Burmańczuk, Artur; Hola, Piotr; Milczak, Andrzej; Piech, Tomasz; Kowalski, Cezary; Wojciechowska, Beata; Grabowski, Tomasz

2018-04-01

Quercetin is a dietary flavonoid which has an effect on inflammation, angiogenesis and vascular inflammation. In several other flavonoids (e.g. kaempferol, astragalin, alpinetin, baicalein, indirubin), anti-inflammatory mechanism was proven by using mice mastitis model. The aim of the current study was pilot analysis of quercetin tolerability and its impact on somatic cells count (SCC) after multiple intramammary treatment on dairy cows with clinical mastitis. Based on SCC and clinical investigation, 9 dairy cows with clinical mastitis of one quarter were selected for the pilot study. Baseline analysis (hematology, TNFα, SCC) was performed every 24h among all cows three days before the first dose (B1-B3). After the baseline monitoring (B1-B3) eight days treatment (D1-D8) was performed with a high and low dose. Selected blood parameters were analyzed. Starting from D1 to D8, a decrease of SCC in relation to baseline was characterized by declining trend. The presented results allowed the confirmation of the significant influence of quercetin on the reduction of SCC in mastitis in dairy cows after 8days of therapy. Copyright © 2018. Published by Elsevier Ltd.

Immunohistochemical expression of basement membrane proteins of verrucous carcinoma of the oral mucosa.

PubMed

Arduino, Paolo G; Carrozzo, Marco; Pagano, Marco; Broccoletti, Roberto; Scully, Crispian; Gandolfo, Sergio

2010-06-01

Squamous cell carcinoma (SCC) of the oral cavity is an extremely invasive tumour of stratified squamous epithelium that spreads throughout degradation of the basement membrane (BM) and extra-cellular matrix. Oral verrucous carcinoma (VC) is a rare low-grade variant of oral SCC that penetrates into the subepithelial connective tissue. It also has a different clinical behaviour from classical oral SCC. We investigated the immunohistochemical expression of laminin, laminin-5, collagen IV and fibronectin in VC, severe epithelial dysplasia (SED) and SCC in order to analyse if the pattern of these molecules expression contributes to the differences in the biological behaviour of these diseases. The staining pattern of laminin was less intensive in SCC compared with SED and VC, and collagen IV expression was increased in VC compared with SED. Discontinuities of laminin, collagen IV and fibronectin were more evident in SED than in VC. This study indicates that VC has a biological behaviour different from SED or SCC, observable by immunohistochemistry in the BM zone.

Nonmelanoma skin cancer in Saudi Arabia: single center experience.

PubMed

AlSalman, Sarah Abdullah; Alkaff, Tuqa Morad; Alzaid, Tariq; Binamer, Yousef

2018-01-01

Skin cancer is the most common cancer worldwide; one in every three diagnosed malignancies is a skin cancer. However, skin cancer is rarely reported in Saudi Arabia so we conducted this study to highlight these underreported neoplasms. Determine the prevalence and patterns of basal cell carcinoma (BCC) and primary squamous cell carcinoma (SCC), the most common types of nonmelanoma skin cancer (NMSC) with respect to age, sex, and anatomic location and to identify potentially associated risk factors. Retrospective, descriptive medical record review. A tertiary care centre. We did a retrospective chart review of all patients diagnosed with basal cell carcinoma and primary squamous cell carcinoma between 2003-2016. Prevalence and pattern of BCC and SCC with respect to age, sex, and anatomic location. Of 593 cases reviewed, 279 had NMSC. Most (95%) were diagnosed with BCC or SCC or both in a few cases. The mean age at diagnosis was 59 (19.5) years. Sixty-two percent of the patients were males. However, 24.3% (n=68) of skin cancers occurred in patients younger than 50 years. The frequency of BCC and SCC was 50.2% and 44.8%, respectively. The head and neck was the most common location (79.6%). In patients younger than 50 years, xeroderma pigmentosum and previously treated solid malignancies were the major factors. BCC and SCC are uncommon but not rare. However, skin cancers are underreported in our population. NMSC in individuals younger than 50 years of age requires more careful evaluation of possible risk factors. Retrospective in a single tertiary care setting.

ΔNp63 activates the Fanconi anemia DNA repair pathway and limits the efficacy of cisplatin treatment in squamous cell carcinoma.

PubMed

Bretz, Anne Catherine; Gittler, Miriam P; Charles, Joël P; Gremke, Niklas; Eckhardt, Ines; Mernberger, Marco; Mandic, Robert; Thomale, Jürgen; Nist, Andrea; Wanzel, Michael; Stiewe, Thorsten

2016-04-20

TP63, a member of the p53 gene family gene, encodes the ΔNp63 protein and is one of the most frequently amplified genes in squamous cell carcinomas (SCC) of the head and neck (HNSCC) and lungs (LUSC). Using an epiallelic series of siRNAs with intrinsically different knockdown abilities, we show that the complete loss of ΔNp63 strongly impaired cell proliferation, whereas partial ΔNp63 depletion rendered cells hypersensitive to cisplatin accompanied by an accumulation of DNA damage. Expression profiling revealed wide-spread transcriptional regulation of DNA repair genes and in particular Fanconi anemia (FA) pathway components such as FANCD2 and RAD18 - known to be crucial for the repair of cisplatin-induced interstrand crosslinks. In SCC patients ΔNp63 levels significantly correlate with FANCD2 and RAD18 expression confirming ΔNp63 as a key activator of the FA pathway in vivo Mechanistically, ΔNp63 bound an upstream enhancer of FANCD2 inactive in primary keratinocytes but aberrantly activated by ΔNp63 in SCC. Consistently, depletion of FANCD2 sensitized to cisplatin similar to depletion of ΔNp63. Together, our results demonstrate that ΔNp63 directly activates the FA pathway in SCC and limits the efficacy of cisplatin treatment. Targeting ΔNp63 therefore would not only inhibit SCC proliferation but also sensitize tumors to chemotherapy. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

The correlated blanching of synaptic bodies and reduction in afferent firing rates caused by transmitter-depleting agents in the frog semicircular canal

NASA Technical Reports Server (NTRS)

Guth, P.; Norris, C.; Fermin, C. D.; Pantoja, M.

1993-01-01

Synaptic bodies (SBs) associated with rings of synaptic vesicles and well-defined, pre- and post-synaptic membrane structures are indicators of maturity in most hair cell-afferent nerve junctions. The role of the SBs remains elusive despite several experiments showing that they may be involved in storage of neurotransmitter. Our results demonstrate that SBs of the adult posterior semicircular canal (SCC) cristae hair cells become less electron dense following incubation of the SCC with the transmitter-depleting drug tetrabenazine (TBZ). Objective quantification and comparison of the densities of the SBs in untreated and TBZ-treated frog SCC demonstrated that TBZ significantly decreased the electron density of SBs. This reduction in electron density was accompanied by a reduction in firing rates of afferent fibers innervating the posterior SCC. A second transmitter-depleting drug, guanethidine, previously shown to reduce the electron density of hair cell SBs, also reduced the firing rates of afferent fibers innervating the posterior SCC. In contrast, the electron density of dense granules (DG), similar in size and shape to synaptic bodies (SB) in hair cells, did not change after incubation in TBZ, thus indicating that granules and SBs are not similar in regard to their electron density. The role of SBs in synaptic transmission and the transmitter, if any, stored in the SBs remain unknown. Nonetheless, the association of the lessening of electron density with a reduction in afferent firing rate provides impetus for the further investigation of the SB's role in neurotransmission.

A Novel Model for Squamous Cell Carcinoma of the Lung | Center for Cancer Research

Cancer.gov

In the U.S. lung cancer remains the most deadly cancer type with less than one in five patients alive five years after diagnosis. The majority of lung cancer deaths are due to tobacco smoke, and the squamous cell carcinoma (SCC) subtype of lung cancer is strongly associated with smoking. Researchers have identified a number of mutations in lung SCC tumors but have failed to

Differentially expressed genes in nonsmall cell lung cancer: expression profiling of cancer-related genes in squamous cell lung cancer.

PubMed

Kettunen, Eeva; Anttila, Sisko; Seppänen, Jouni K; Karjalainen, Antti; Edgren, Henrik; Lindström, Irmeli; Salovaara, Reijo; Nissén, Anna-Maria; Salo, Jarmo; Mattson, Karin; Hollmén, Jaakko; Knuutila, Sakari; Wikman, Harriet

2004-03-01

The expression patterns of cancer-related genes in 13 cases of squamous cell lung cancer (SCC) were characterized and compared with those in normal lung tissue and 13 adenocarcinomas (AC), the other major type of nonsmall cell lung cancer (NSCLC). cDNA array was used to screen the gene expression levels and the array results were verified using a real-time reverse-transcriptase-polymerase chain reaction (RT-PCR). Thirty-nine percent of the 25 most upregulated and the 25 most downregulated genes were common to SCC and AC. Of these genes, DSP, HMGA1 (alias HMGIY), TIMP1, MIF, CCNB1, TN, MMP11, and MMP12 were upregulated and COPEB (alias CPBP), TYROBP, BENE, BMPR2, SOCS3, TIMP3, CAV1, and CAV2 were downregulated. The expression levels of several genes from distinct protein families (cytokeratins and hemidesmosomal proteins) were markedly increased in SCC compared with AC and normal lung. In addition, several genes, overexpressed in SCC, such as HMGA1, CDK4, IGFBP3, MMP9, MMP11, MMP12, and MMP14, fell into distinct chromosomal loci, which we have detected as gained regions on the basis of comparative genomic hybridization data. Our study revealed new candidate genes involved in NSCLC.

Cow characteristics and their association with udder health after different dry period lengths.

PubMed

van Hoeij, R J; Lam, T J G M; de Koning, D B; Steeneveld, W; Kemp, B; van Knegsel, A T M

2016-10-01

Shortening or omitting the dry period (DP) in dairy cows is of interest because of potential beneficial effects on energy balance and metabolic health. Reported effects of a short or omitted dry period on udder health are ambiguous. This study aimed to evaluate the effect of no DP (0d), a short DP (30d), or a conventional DP (60 d) on the occurrence of intramammary infections (IMI) during the precalving period and on somatic cell counts (SCC), elevations of SCC (SCC≥200,000 cells/mL), and clinical mastitis in the subsequent lactation. The study also aimed to analyze which prepartum cow characteristics are associated with udder health after different DP lengths. Holstein-Friesian dairy cows (n=167) were randomly assigned to a DP length (0, 30, or 60 d). Cows with a 0-d DP had a greater occurrence of chronic IMI and a lower occurrence of cured IMI during the precalving period than cows with a 30-d or 60-d DP. Postpartum average SCC for lactation was greater in cows with a 0-d DP than in cows with a 30-d or 60-d DP. The number of cows with at least 1 elevation of SCC, the number of elevations of SCC per affected cow, the number of cows treated for clinical mastitis, and the number of cases of mastitis per affected cow did not differ among DP lengths. Cow characteristics related to postpartum average SCC for lactation were DP length, parity, and the following interactions: DP length with prepartum elevation of SCC, DP length with fat- and protein-corrected milk (FPCM) reduction between 150 and 67d prepartum, DP length with parity and with average SCC for lactation, and last FPCM before the conventional drying-off day with average SCC for lactation. Cows with prepartum parity 1 had a lower occurrence of at least 1 elevation of SCC in subsequent lactation compared with cows with parity >2. Last SCC before the conventional drying-off day was positively associated with occurrence of clinical mastitis in the subsequent lactation. In this study, DP length was not a risk factor for either elevation of SCC or occurrence of clinical mastitis in the subsequent lactation. The identified cow characteristics could be used in a decision support model to optimize DP length for individual cows. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Primary frontal sinus squamous cell carcinoma in three dogs treated with piroxicam combined with carboplatin or toceranib.

PubMed

de Vos, J; Ramos Vega, S; Noorman, E; de Vos, P

2012-09-01

In human medicine, primary frontal sinus squamous cell carcinoma (pFS-SCC) is not frequently reported. In veterinary medicine, frontal sinus SCC is exclusively described as an extension of nasal cavity SCC. To our knowledge, this is the first publication concerning canine pFS-SCC, diagnosed using histology or cytology and medical imaging, in three dogs. The tumours extended into the orbit or brain cavity, without nasal involvement. Treatment was initiated with piroxicam-carboplatin. Prolongation of carboplatin delivery with a low dose intensity was performed on dogs with a favourable initial response. Dog 1 achieved a complete remission (CR), but was euthanized 344 days after start of therapy. Dog 2, still alive 3 years after start of therapy and in CR, received 14 carboplatin deliveries. In dog 3, after changing the treatment protocol into piroxicam-toceranib, a significant tumour reduction occurred, but the dog was euthanized after 195 days because of a relapse. © 2011 Blackwell Publishing Ltd.

A potential role for zinc transporter 7 in testosterone synthesis in mouse Leydig tumor cells.

PubMed

Chu, Qingqing; Chi, Zhi-Hong; Zhang, Xiuli; Liang, Dan; Wang, Xuemei; Zhao, Yue; Zhang, Li; Zhang, Ping

2016-06-01

Previous studies have demonstrated that zinc (Zn) is an essential trace element which is involved in male reproduction. The zinc transporter (ZnT) family, SLC30a, is involved in the maintenance of Zn homeostasis and in mediating intracellular signaling events; however, relatively little is known regarding the effect of ZnTs on testosterone synthesis. Thus, in the present study, we aimed to determine the effect of Zn transporter 7 (ZnT7) on testosterone synthesis in male CD-1 mice and mouse Leydig cells. The findings of the present study revealed that the concentrations of Zn in the testes and Leydig cells were significantly lower in mice fed a Zn-deficient diet compared with the control mice fed a Zn-adequate diet. In addition, ZnT7 was principally expressed and colocalized with steroidogenic acute regulatory protein (StAR) in the Leydig cells of male CD-1 mice. ZnT7 expression was downregulated in the mice fed a Zn-deficient diet, which led to decreases in the expression of the enzymes involved in testosterone synthesis namely cholesterol side‑chain cleavage enzyme (P450scc) and 3β-hydroxysteroid dehydrogenase/D5-D4 isomerase (3β-HSD) as well as decreased serum testosterone levels. These results suggested that Znt7 may be involved in testosterone synthesis in the mouse testes. To examine this hypothesis, we used the mouse Leydig tumor cell line (MLTC-1 cell line) in which the ZnT7 gene had been silenced, in order to gauge the impact of changes in ZnT7 expression on testosterone secretion and the enzymes involved in testosterone synthesis. The results demonstrated that ZnT7 gene silencing downregulated the expression of StAR, P450scc and 3β-HSD as well as progesterone concentrations in the human chorionic gonadotrophin (hCG)-stimulated MLTC-1 cells. Taken together, these findings reveal that ZnT7 may play an important role in the regulation of testosterone synthesis by modulating steroidogenic enzymes, and may represent a therapeutic target in testosterone deficiency.

Oral cancer/endothelial cell fusion experiences nuclear fusion and acquisition of enhanced survival potential

DOE Office of Scientific and Technical Information (OSTI.GOV)

Song, Kai; The State Key Laboratory Breeding Base of Basic Science of Stomatology; Song, Yong

Most previous studies have linked cancer–macrophage fusion with tumor progression and metastasis. However, the characteristics of hybrid cells derived from oral cancer and endothelial cells and their involvement in cancer remained unknown. Double-immunofluorescent staining and fluorescent in situ hybridization (FISH) were performed to confirm spontaneous cell fusion between eGFP-labeled human umbilical vein endothelial cells (HUVECs) and RFP-labeled SCC9, and to detect the expression of vementin and cytokeratin 18 in the hybrids. The property of chemo-resistance of such hybrids was examined by TUNEL assay. The hybrid cells in xenografted tumor were identified by FISH and GFP/RFP dual-immunofluoresence staining. We showed thatmore » SCC9 cells spontaneously fused with cocultured endothelial cells, and the resultant hybrid cells maintained the division and proliferation activity after re-plating and thawing. Such hybrids expressed markers of both parental cells and became more resistant to chemotherapeutic drug cisplatin as compared to the parental SCC9 cells. Our in vivo data indicated that the hybrid cells contributed to tumor composition by using of immunostaining and FISH analysis, even though the hybrid cells and SCC9 cells were mixed with 1:10,000, according to the FACS data. Our study suggested that the fusion events between oral cancer and endothelial cells undergo nuclear fusion and acquire a new property of drug resistance and consequently enhanced survival potential. These experimental findings provide further supportive evidence for the theory that cell fusion is involved in cancer progression. - Highlights: • The fusion events between oral cancer and endothelial cells undergo nuclear fusion. • The resulting hybrid cells acquire a new property of drug resistance. • The resulting hybrid cells express the markers of both parental cells (i.e. vimentin and cytokeratin 18). • The hybrid cells contribute to tumor repopulation in vivo.« less

Inactivated Wnt signaling in resveratrol-treated epidermal squamous cancer cells and its biological implication

PubMed Central

Liu, Zhi-Li; Li, Hong; Liu, Jia; Wu, Mo-Li; Chen, Xiao-Yan; Liu, Li-Hong; Wang, Qian

2017-01-01

Squamous cell carcinoma (SCC) is the most common epidermal malignancy, and Wnt/β-catenin signaling is frequently activated in SCC. Resveratrol prevents rodent epidermal carcinogenesis, while its effect on human epidermal cancer remains unknown. To address this issue, the impact of resveratrol on the growth and Wnt signaling of skin SCC Colo16 cells were investigated at the cellular and molecular biology levels by flow cytometry, immunocytochemistry, reverse transcription-polymerase chain reaction, western blotting and β-catenin-specific small interfering RNA (siRNA) transfection. Resveratrol (100 µM) suppressed cell growth and induced apoptosis in Colo16 cells. Wnt2 and its downstream genes were downregulated, which was accompanied by increased expression of the Wnt signaling inhibitor Axin2. Transfection with a β-catenin-specific siRNA did not affect cell growth but enhanced the resveratrol susceptibility of Colo16 transfectants. The present results suggest the inhibitory effects of resveratrol on epidermal SCCs and inactivation of Wnt signaling as one of the resveratrol-caused molecular events in Colo16 cells. β-catenin oriented siRNA is insufficient to induce cell crisis, implicating the presence of more critical cancer-associated element(s) as the target in Colo16 cells. PMID:28781663

Transcriptional regulation of ataxia-telangiectasia and Rad3-related protein by activated p21-activated kinase-1 protects keratinocytes in UV-B-induced premalignant skin lesions.

PubMed

Beesetti, S; Mavuluri, J; Surabhi, R P; Oberyszyn, T M; Tober, K; Pitani, R S; Joseph, L D; Venkatraman, G; Rayala, S K

2017-11-02

Sun-induced skin lesions, in particular actinic keratosis, are generally considered as premalignant skin lesions that can progress into squamous cell carcinoma (SCC) and invasive SCC if left untreated. Therefore, understanding the molecular mechanisms by which the ultraviolet-B (UV-B)-exposed cells are being protected and the signaling pathways that promote the progression of certain premalignant skin lesions to malignant lesions will permit us to prevent or cure skin cancers. In the current study, we found that phospho-p21-activated kinase-1 (Pak1) and Pak1 expression was high in clinical samples of sunlight-induced premalignant skin lesions assessed by immunohistochemistry. Further, we observed that phospho-Pak1 and Pak1 levels are high in UV-B-exposed hairless SKH mouse model skin samples as compared with unexposed skin tissue. Our results from cell line and animal models showed that Pak1 is activated in response to UV-B radiation, and this activated Pak1 translocates from the cytoplasm to the nucleus. Inside the nucleus, Pak1 via C-Fos binds to a specific promoter region of DNA repair kinase ATR (ataxia-telangiectasia and Rad3-related protein) and acts as a transcriptional regulator of ATR. Results from our analysis showed that Pak1 overexpression, knockdown and Pak1 knockout cell line models showed that Pak1 confers protection to keratinocytes from UV-B-induced apoptosis and DNA damage via ATR. To our knowledge, this is the first study that evaluates the functional and clinical significance of a signaling molecule, Pak1, in sun-induced premalignant skin lesions and indicates that increased Pak1 activation and expression could serve as an early warning sign of progression toward non-melanoma skin cancer, if ignored.

The LSH/HELLS homolog Irc5 contributes to cohesin association with chromatin in yeast

PubMed Central

Bakowski, Tomasz; Maciaszczyk-Dziubinska, Ewa; Wysocki, Robert

2017-01-01

Abstract Accurate chromosome segregation is essential for every living cell as unequal distribution of chromosomes during cell division may result in genome instability that manifests in carcinogenesis and developmental disorders. Irc5 from Saccharomyces cerevisiae is a member of the conserved Snf2 family of ATP-dependent DNA translocases and its function is poorly understood. Here, we identify Irc5 as a novel interactor of the cohesin complex. Irc5 associates with Scc1 cohesin subunit and contributes to cohesin binding to chromatin. Disruption of IRC5 decreases cohesin levels at centromeres and chromosome arms, causing premature sister chromatid separation. Moreover, reduced cohesin occupancy at the rDNA region in cells lacking IRC5 leads to the loss of rDNA repeats. We also show that the translocase activity of Irc5 is required for its function in cohesion pathway. Finally, we demonstrate that in the absence of Irc5 both the level of chromatin-bound Scc2, a member of cohesin loading complex, and physical interaction between Scc1 and Scc2 are reduced. Our results suggest that Irc5 is an auxiliary factor that is involved in cohesin association with chromatin. PMID:28383696

Inecalcitol, an analog of 1,25D₃, displays enhanced antitumor activity through the induction of apoptosis in a squamous cell carcinoma model system

PubMed Central

Ma, Yingyu; Yu, Wei-Dong; Hidalgo, Alejandro A.; Luo, Wei; Delansorne, Remi; Johnson, Candace S.; Trump, Donald L.

2013-01-01

Epidemiological data suggest an important role of vitamin D signaling in cancer development and progression, and experimental studies demonstrate that the active vitamin D metabolite 1α, 25-dihydroxyvitamin D₃ (1,25D₃) has broad spectrum antitumor activity. Hypercalcemia has often been suggested to limit the clinical application of these data. The 14-epi-analog of 1,25D₃, inecalcitol [19-nor-14-epi-23-yne-1,25-(OH)₂D₃; TX522], was developed to have superagonistic antitumor activities but low hypercalcemia potential. We examined the antitumor activity of inecalcitol and the underlying mechanisms in a murine squamous cell carcinoma (SCC) model system. In vitro, compared with 1,25D₃, inecalcitol showed enhanced vitamin D receptor (VDR)-mediated transcriptional activity. Inecalcitol suppressed SCC cell proliferation in a dose-dependent manner with an IC₅₀ value 30 times lower than that of 1,25D₃. Both inecalcitol and 1,25D₃ induced a comparable level of G₀/G₁ cell cycle arrest in SCC cells. The level of apoptosis induced by inecalcitol was markedly higher than that of 1,25D₃. Apoptosis was mediated through the activation of the caspase 8/10- caspase 3 pathway. Further, inecalcitol markedly inhibited the mRNA and protein expression of c-IAP1 and XIAP compared with 1,25D₃. In vivo, inecalcitol inhibits SCC tumor growth in a dose-dependent fashion. Notably, inecalcitol induced a significantly higher level of apoptosis in the SCC xenograft model. While in vitro inecalcitol demonstrates apparent enhanced VDR binding and antiproliferative effects compared to 1,25D₃, in vivo these advantages disappear; at doses of inecalcitol that have equivalent antitumor effects, similar hypercalcemia is seen. This may be explained by the pharmacokinetics of 1,25D₃ vs. inecalcitol and attributed to the much shorter serum half-life of inecalcitol.We show that inecalcitol has potent antitumor activity in the SCC model system, and this is associated with a strong induction of apoptosis. These findings support the further development of inecalcitol in cancer treatment. PMID:23388458

SU-G-TeP3-10: Radiation Induces Prompt Live-Cell Metabolic Fluxes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Campos, D; Peeters, W; Bussink, J

2016-06-15

Purpose: To compare metabolic dynamics and HIF-1α expression following radiation between a cancerous cell line (UM-SCC-22B) and a normal, immortalized cell line, NOK (Normal Oral Keratinocyte). HIF-1 is a key factor in metabolism and radiosensitivity. A better understanding of how radiation affects the interplay of metabolism and HIF-1 might give a better understanding of the mechanisms responsible for radiosensitivity. Methods: Changes in cellular metabolism in response to radiation are tracked by fluorescence lifetime of NADH. Expression of HIF-1α was measured by immunofluorescence for both cell lines with and without irradiation. Radiation response is also monitored with additional treatment of amore » HIF-1α inhibitor (chrysin) as well as a radical scavenger (glutathione). Changes in oxygen consumption and respiratory capacity are also monitored using the Seahorse XF analyzer. Results: An increase in HIF-1α was found to be in response to radiation for the cancer cell line, but not the normal cell line. Radiation was found to shift metabolism toward glycolytic pathways in cancer cells as measured by oxygen consumption and respiratory capacity. Radiation response was found to be muted by addition of glutathione to cell media. HIF-1α inhibition similarly muted radiation response in cancer. Conclusion: The HIF-1 protein complex is a key regulator cellular metabolism through the regulation of glycolysis and glucose transport enzymes. Moreover, HIF-1 has shown radio-protective effects in tumor vascular endothelia, and has been implicated in metastatic aggression. Monitoring interplay between metabolism and the HIF-1 protein complex can give a more fundamental understanding of radiotherapy response.« less

Structure of the Pds5-Scc1 Complex and Implications for Cohesin Function.

PubMed

Muir, Kyle W; Kschonsak, Marc; Li, Yan; Metz, Jutta; Haering, Christian H; Panne, Daniel

2016-03-08

Sister chromatid cohesion is a fundamental prerequisite to faithful genome segregation. Cohesion is precisely regulated by accessory factors that modulate the stability with which the cohesin complex embraces chromosomes. One of these factors, Pds5, engages cohesin through Scc1 and is both a facilitator of cohesion, and, conversely also mediates the release of cohesin from chromatin. We present here the crystal structure of a complex between budding yeast Pds5 and Scc1, thus elucidating the molecular basis of Pds5 function. Pds5 forms an elongated HEAT repeat that binds to Scc1 via a conserved surface patch. We demonstrate that the integrity of the Pds5-Scc1 interface is indispensable for the recruitment of Pds5 to cohesin, and that its abrogation results in loss of sister chromatid cohesion and cell viability. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Host characteristics, sun exposure, indoor tanning and risk of squamous cell carcinoma of the skin.

PubMed

Veierød, Marit B; Couto, Elisabeth; Lund, Eiliv; Adami, Hans-Olov; Weiderpass, Elisabete

2014-07-15

Use of indoor tanning devices increases risk of cutaneous malignant melanoma, but the association with risk of squamous cell carcinoma (SCC) of the skin is unclear. Cohort studies of SCC risk are rare and we aimed to assess the association between SCC risk and host characteristics, sun exposure, and indoor tanning in a population-based cohort of Norwegian and Swedish women conjunctly with SCC incidence data from national cancer registries. Host characteristics and exposure to sun and indoor tanning devices before 50-years old were recorded by questionnaire at inclusion (30-50 years) in 1991/92. Multivariable relative risks (RRs) and 95% confidence intervals (CIs) were estimated by Poisson regression. During follow-up of 106,548 women through December 2009, SCC was diagnosed in 141 women. Skin sensitivity to acute sun exposure was the most important pigmentation characteristic (RR = 2.73, 95% CI 1.47-5.05, for red with pain/red with pain and blisters versus brown). We found no consistent associations with sunburns and bathing vacations in the first five age decades, but a significant positive trend for bathing vacations summarized over ages 10-49 years (Ptrend  = 0.02). We also found significantly increased risks of SCC following indoor tanning at age 40-49 years (RR = 2.17, 95% CI 1.29-3.67, for ≥ 1 time/month versus never) and indoor tanning summarized over ages 10-49 years (Ptrend  = 0.001). RR for ever versus never use of indoor tanning over ages 10-49 years was 1.93 (95% CI 1.27-2.95). Propensity to burn was an important host characteristic, and bathing vacations and indoor tanning summarized over ages 10-49 years increased SCC risk. © 2013 UICC.

A population-based case-control study of urinary arsenic species and squamous cell carcinoma in New Hampshire, USA.

PubMed

Gilbert-Diamond, Diane; Li, Zhigang; Perry, Ann E; Spencer, Steven K; Gandolfi, A Jay; Karagas, Margaret R

2013-10-01

Chronic high arsenic exposure is associated with squamous cell carcinoma (SCC) of the skin, and inorganic arsenic (iAs) metabolites may play an important role in this association. However, little is known about the carcinogenicity of arsenic at levels commonly observed in the United States. We estimated associations between total urinary arsenic and arsenic species and SCC in a U.S. population. We conducted a population-based case-control SCC study (470 cases, 447 controls) in a U.S. region with moderate arsenic exposure through private well water and diet. We measured urinary iAs, monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA), and summed these arsenic species (ΣAs). Because seafood contains arsenolipids and arsenosugars that metabolize into DMA through alternate pathways, participants who reported seafood consumption within 2 days before urine collection were excluded from the analyses. In adjusted logistic regression analyses (323 cases, 319 controls), the SCC odds ratio (OR) was 1.37 for each ln-transformed microgram per liter increase in ln-transformed ΣAs concentration [ln(ΣAs)] (95% CI: 1.04, 1.80). Urinary ln(MMA) and ln(DMA) also were positively associated with SCC (OR = 1.34; 95% CI: 1.04, 1.71 and OR = 1.34; 95% CI: 1.03, 1.74, respectively). A similar trend was observed for ln(iAs) (OR = 1.20; 95% CI: 0.97, 1.49). Percent iAs, MMA, and DMA were not associated with SCC. These results suggest that arsenic exposure at levels common in the United States relates to SCC and that arsenic metabolism ability does not modify the association.

Marriage, cohabitation and incidence trends of invasive penile squamous cell carcinoma in Denmark 1978-2010.

PubMed

Ulff-Møller, Constance J; Simonsen, Jacob; Frisch, Morten

2013-09-01

Few population-based studies have investigated the relation between living arrangements and risk of invasive penile squamous cell carcinoma (iP-SCC). Using long-term national cancer registry data in Denmark we examined incidence trends of iP-SCC. Furthermore, we examined the relation between marital status, cohabitation status and risk of iP-SCC using hazard ratios (HRs) with 95% confidence intervals (CIs) obtained in Cox proportional hazards regression analyses as our measure of relative risk. Overall, 1,292 cases of iP-SCC were identified during 65.6 million person-years of observation between 1978 and 2010. During this period, the WHO world age-standardized incidence remained relatively stable (p-trend = 0.41) with an average incidence of 1.05 cases per 100,000 person-years. When compared to married men, those who were unmarried (HR 1.37; 95% CI: 1.13-1.66), divorced (HR 1.49; 95% CI: 1.24-1.79) or widowed (HR 1.36; 95% CI: 1.13-1.63) were at increased risk of iP-SCC. Regarding cohabitation status, single-living men were at increased risk of iP-SCC compared to men in opposite-sex cohabitation (HR 1.43; 95% CI: 1.26-1.62). Risk increased with increasing numbers of prior opposite-sex (p-trend = 0.02) and same-sex (p-trend < 0.001) cohabitations. In conclusion, single-living Danish men and men who are not currently married are at increased risk of iP-SCC, and the risk increases with the number of prior cohabitations, perhaps reflecting less stable sexual relations in these subgroups. Copyright © 2013 UICC.

Patterns of Ultraviolet Radiation Exposure and Skin Cancer Risk: the E3N-SunExp Study.

PubMed

Savoye, Isabelle; Olsen, Catherine M; Whiteman, David C; Bijon, Anne; Wald, Lucien; Dartois, Laureen; Clavel-Chapelon, Françoise; Boutron-Ruault, Marie-Christine; Kvaskoff, Marina

2018-01-05

While ultraviolet (UV) radiation exposure is a recognized risk factor for skin cancer, associations are complex and few studies have allowed a direct comparison of exposure profiles associated with cutaneous melanoma, basal-cell carcinoma (BCC), and squamous-cell carcinoma (SCC) within a single population. We examined associations between UV exposures and skin cancer risk in a nested case-control study within E3N, a prospective cohort of 98,995 French women born in 1925-1950. In 2008, a lifetime UV exposure questionnaire was sent to all reported skin cancer cases and three controls per case, which were matched on age, county of birth, and education. Analyses were performed using conditional logistic regression and included 366 melanoma cases, 1,027 BCC cases, 165 SCC cases, and 3,647 controls. A history of severe sunburns <25 years was associated with increased risks of all skin cancers (melanoma: OR 2.7; BCC: OR 1.7; SCC: OR 2.0 for ≥6 sunburns vs. none), while sunburns ≥25 years were associated with BCC and SCC only. While high-sun protection factor sunscreen use before age 25 was associated with lower BCC risk (P trend = 0.02), use since age 25 and reapplication of sunscreen were associated with higher risks of all three types of skin cancer. There were positive linear associations between total UV score and risks of BCC (P trend = 0.01) and SCC (P trend = 0.09), but not melanoma. While recreational UV score was strongly associated with BCC, total and residential UV scores were more strongly associated with SCC. Melanoma, BCC, and SCC are associated with different sun exposure profiles in women.

Protein kinase C delta overexpressing transgenic mice are resistant to chemically but not to UV radiation-induced development of squamous cell carcinomas: a possible link to specific cytokines and cyclooxygenase-2.

PubMed

Aziz, Moammir H; Wheeler, Deric L; Bhamb, Bhushan; Verma, Ajit K

2006-01-15

Protein kinase C delta (PKCdelta), a Ca(2+)-independent, phospholipid-dependent serine/threonine kinase, is among the novel PKCs (delta, epsilon, and eta) expressed in mouse epidermis. We reported that FVB/N transgenic mice that overexpress ( approximately 8-fold) PKCdelta protein in basal epidermal cells and cells of the hair follicle are resistant to the development of both skin papillomas and squamous cell carcinoma (SCC) elicited by 7,12-dimethylbenz(a)anthracene initiation and 12-O-tetradecanoylphorbol-13-acetate (TPA) promotion protocol. We now present that PKCdelta overexpression in transgenic mice failed to suppress the induction of SCC developed by repeated exposures to UV radiation (UVR), the environmental carcinogen linked to the development of human SCC. Both TPA and UVR treatment of wild-type mice (a) increased the expression of proliferating cell nuclear antigen (PCNA) and apoptosis; (b) stimulated the expression of cytokines tumor necrosis factor-alpha (TNF-alpha), granulocyte macrophage colony-stimulating factor (GM-CSF), and granulocyte CSF (G-CSF); and (c) increased cyclooxygenase-2 (COX-2) expression and expression of phosphorylated Akt (p-Akt), p38, extracellular signal-regulated kinase-1 (ERK1), and ERK2. PKCdelta overexpression in transgenic mice enhanced TPA-induced but not UVR-induced apoptosis and suppressed TPA-stimulated but not UVR-stimulated levels of cell PCNA, cytokines (TNF-alpha, G-CSF, and GM-CSF), and the expression of COX-2, p-Akt, and p38. The results indicate that UVR-mediated signal transduction pathway to the induction of SCC does not seem to be sensitive to PKCdelta overexpression. The proapoptotic activity of PKCdelta coupled with its ability to suppress TPA-induced expression of proinflammatory cytokines, COX-2 expression, and the phosphorylation of Akt and p38 may play roles in the suppression of TPA-promoted development of SCC.

Trends in incidence, mortality and survival of penile squamous cell carcinoma in Norway 1956-2015.

PubMed

Hansen, Bo T; Orumaa, Madleen; Lie, A Kathrine; Brennhovd, Bjørn; Nygård, Mari

2018-04-15

We examine trends in incidence, mortality and survival of penile squamous cell carcinoma (SCC) in Norway over 60 years. Data on all cases of penile cancer diagnosed in Norway during 1956-2015 were obtained from the Cancer Registry of Norway. Trends in age-standardized rates of penile SCC incidence, mortality and 5-year relative survival were assessed by the annual percentage change statistic and joinpoint regression. A total of 1,596 penile cancer cases were diagnosed during 1956-2015, among which 1,474 (92.4%) were SCC. During 2011-2015, the age-standardized incidence and mortality of penile SCC were 0.91 (95% confidence interval (CI): 0.78; 1.05) and 0.50 (0.42; 0.60) per 100,000, respectively, and the 5-year relative survival was 61.6% (41.9; 76.4). The incidence of SCC increased during 1956-2015, with an average annual percentage change (AAPC) of 0.80% (0.46; 1.15). The increase was strongest among men diagnosed at a relatively early age (age<=64 years; AAPC: 1.47% (0.90; 2.05)). Mortality also increased over the study period (AAPC: 0.47% (0.10; 0.85)), whereas 5-year relative survival did not change (AAPC: 0.08% (-0.19; 0.36)). We conclude that the incidence of penile SCC has increased at a moderate and constant rate during 1956-2015, and that the most consistent increase occurred among younger men. Mortality also increased during the study period. However, survival did not change, thus changes in diagnostics and treatment had little impact on survival from penile SCC. Since a substantial proportion of penile SCC is caused by human papillomavirus (HPV), the incidence increase may in part be attributed to increased exposure to HPV in the population. © 2017 The Authors International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.

Trends in incidence, mortality and survival of penile squamous cell carcinoma in Norway 1956–2015

PubMed Central

Orumaa, Madleen; Lie, A. Kathrine; Brennhovd, Bjørn; Nygård, Mari

2017-01-01

We examine trends in incidence, mortality and survival of penile squamous cell carcinoma (SCC) in Norway over 60 years. Data on all cases of penile cancer diagnosed in Norway during 1956–2015 were obtained from the Cancer Registry of Norway. Trends in age‐standardized rates of penile SCC incidence, mortality and 5‐year relative survival were assessed by the annual percentage change statistic and joinpoint regression. A total of 1,596 penile cancer cases were diagnosed during 1956–2015, among which 1,474 (92.4%) were SCC. During 2011–2015, the age‐standardized incidence and mortality of penile SCC were 0.91 (95% confidence interval (CI): 0.78; 1.05) and 0.50 (0.42; 0.60) per 100,000, respectively, and the 5‐year relative survival was 61.6% (41.9; 76.4). The incidence of SCC increased during 1956–2015, with an average annual percentage change (AAPC) of 0.80% (0.46; 1.15). The increase was strongest among men diagnosed at a relatively early age (age<=64 years; AAPC: 1.47% (0.90; 2.05)). Mortality also increased over the study period (AAPC: 0.47% (0.10; 0.85)), whereas 5‐year relative survival did not change (AAPC: 0.08% (−0.19; 0.36)). We conclude that the incidence of penile SCC has increased at a moderate and constant rate during 1956–2015, and that the most consistent increase occurred among younger men. Mortality also increased during the study period. However, survival did not change, thus changes in diagnostics and treatment had little impact on survival from penile SCC. Since a substantial proportion of penile SCC is caused by human papillomavirus (HPV), the incidence increase may in part be attributed to increased exposure to HPV in the population. PMID:29205336

Incidence and relative risk of cutaneous squamous cell carcinoma with single-agent BRAF inhibitor and dual BRAF/MEK inhibitors in cancer patients: a meta-analysis

PubMed Central

Peng, Ling; Wang, Yina; Hong, Yun; Ye, Xianghua; Shi, Peng; Zhang, Junyan; Zhao, Qiong

2017-01-01

Background BRAF inhibitor and dual BRAF/MEK inhibitors have been approved for the treatment of BRAF-mutated melanoma. Cutaneous squamous cell carcinoma (cuSCC) is an adverse event associated with these drugs. The contribution of BRAF inhibitor and dual BRAF/MEK inhibitors to cuSCC are still unknown. We performed this meta-analysis to determine the overall incidence and relative risk of cuSCC in cancer patients treated with these drugs. Results A total of 7,442 patients from 24 primary studies were included. The incidences of all-grade and high-grade cuSCC in cancer patients treated with BRAF inhibitor were 12.5% (95% CI: 10.8–14.6%) and 11.6% (95% CI: 9.8–13.8%), and dual BRAF/MEK inhibitors were 3.0% (95% CI: 2.0–4.5%) and 2.8% (95% CI: 1.9–4.0%), respectively. On subgroup analysis and meta-regression, the incidence of cuSCC did not vary with tumor type, study design and specific drug used. The use of single agent BRAF inhibitor significantly increased the risk of developing cuSCC comparing with dual BRAF/MEK inhibitors for all-grade (RR 4.72, 95% CI: 2.42–9.20) and high-grade (RR 4.92, 95% CI: 2.64–9.16) in cancer patients. Materials and Methods The databases of PubMed, Embase and abstracts published in ASCO proceedings were searched for relevant studies from January 2000 to June 2017. Summary incidences, relative risks (RRs) and 95% confidence intervals (CIs) were calculated by using either random effects or fixed effect models according to the heterogeneity of included studies. Conclusions BRAF inhibitor significantly increases the risk of developing cuSCC compared with dual BRAF/MEK inhibitors in cancer patients. Clinicians should be aware of the risks of cuSCC with the administration of these drugs in cancer patients. PMID:29137342

Overexpression of the Steroidogenic Enzyme Cytochrome P450 Side Chain Cleavage in the Ventral Tegmental Area Increases 3α,5α-THP and Reduces Long-Term Operant Ethanol Self-Administration

PubMed Central

Cook, Jason B.; Werner, David F.; Maldonado-Devincci, Antoniette M.; Leonard, Maggie N.; Fisher, Kristen R.; O'Buckley, Todd K.; Porcu, Patrizia; McCown, Thomas J.; Besheer, Joyce; Hodge, Clyde W.

2014-01-01

Neuroactive steroids are endogenous neuromodulators capable of altering neuronal activity and behavior. In rodents, systemic administration of endogenous or synthetic neuroactive steroids reduces ethanol self-administration. We hypothesized this effect arises from actions within mesolimbic brain regions that we targeted by viral gene delivery. Cytochrome P450 side chain cleavage (P450scc) converts cholesterol to pregnenolone, the rate-limiting enzymatic reaction in neurosteroidogenesis. Therefore, we constructed a recombinant adeno-associated serotype 2 viral vector (rAAV2), which drives P450scc expression and neuroactive steroid synthesis. The P450scc-expressing vector (rAAV2-P450scc) or control GFP-expressing vector (rAAV2-GFP) were injected bilaterally into the ventral tegmental area (VTA) or nucleus accumbens (NAc) of alcohol preferring (P) rats trained to self-administer ethanol. P450scc overexpression in the VTA significantly reduced ethanol self-administration by 20% over the 3 week test period. P450scc overexpression in the NAc, however, did not alter ethanol self-administration. Locomotor activity was unaltered by vector administration to either region. P450scc overexpression produced a 36% increase in (3α,5α)-3-hydroxypregnan-20-one (3α,5α-THP, allopregnanolone)-positive cells in the VTA, but did not increase 3α,5α-THP immunoreactivity in NAc. These results suggest that P450scc overexpression and the resultant increase of 3α,5α-THP-positive cells in the VTA reduces ethanol reinforcement. 3α,5α-THP is localized to neurons in the VTA, including tyrosine hydroxylase neurons, but not astrocytes. Overall, the results demonstrate that using gene delivery to modulate neuroactive steroids shows promise for examining the neuronal mechanisms of moderate ethanol drinking, which could be extended to other behavioral paradigms and neuropsychiatric pathology. PMID:24760842

Overexpression of the steroidogenic enzyme cytochrome P450 side chain cleavage in the ventral tegmental area increases 3α,5α-THP and reduces long-term operant ethanol self-administration.

PubMed

Cook, Jason B; Werner, David F; Maldonado-Devincci, Antoniette M; Leonard, Maggie N; Fisher, Kristen R; O'Buckley, Todd K; Porcu, Patrizia; McCown, Thomas J; Besheer, Joyce; Hodge, Clyde W; Morrow, A Leslie

2014-04-23

Neuroactive steroids are endogenous neuromodulators capable of altering neuronal activity and behavior. In rodents, systemic administration of endogenous or synthetic neuroactive steroids reduces ethanol self-administration. We hypothesized this effect arises from actions within mesolimbic brain regions that we targeted by viral gene delivery. Cytochrome P450 side chain cleavage (P450scc) converts cholesterol to pregnenolone, the rate-limiting enzymatic reaction in neurosteroidogenesis. Therefore, we constructed a recombinant adeno-associated serotype 2 viral vector (rAAV2), which drives P450scc expression and neuroactive steroid synthesis. The P450scc-expressing vector (rAAV2-P450scc) or control GFP-expressing vector (rAAV2-GFP) were injected bilaterally into the ventral tegmental area (VTA) or nucleus accumbens (NAc) of alcohol preferring (P) rats trained to self-administer ethanol. P450scc overexpression in the VTA significantly reduced ethanol self-administration by 20% over the 3 week test period. P450scc overexpression in the NAc, however, did not alter ethanol self-administration. Locomotor activity was unaltered by vector administration to either region. P450scc overexpression produced a 36% increase in (3α,5α)-3-hydroxypregnan-20-one (3α,5α-THP, allopregnanolone)-positive cells in the VTA, but did not increase 3α,5α-THP immunoreactivity in NAc. These results suggest that P450scc overexpression and the resultant increase of 3α,5α-THP-positive cells in the VTA reduces ethanol reinforcement. 3α,5α-THP is localized to neurons in the VTA, including tyrosine hydroxylase neurons, but not astrocytes. Overall, the results demonstrate that using gene delivery to modulate neuroactive steroids shows promise for examining the neuronal mechanisms of moderate ethanol drinking, which could be extended to other behavioral paradigms and neuropsychiatric pathology.

Mast cells and matrix metalloproteinase 9 expression in actinic cheilitis and lip squamous cell carcinoma.

PubMed

Souza Freitas, Valéria; de Andrade Santos, Pedro Paulo; de Almeida Freitas, Roseana; Pereira Pinto, Leão; de Souza, Lélia Batista

2011-09-01

The aim of this study was to evaluate mast cell (MC) density and migration and their association with matrix metalloproteinase (MMP) 9 expression in squamous cell carcinoma (SCC) and actinic cheilitis (AC). Tryptase, c-Kit, and MMP-9 expression was evaluated in 20 cases of SCC, 20 cases of AC, and 7 cases of normal lip (control samples) by immunohistochemistry techniques. Tryptase(+) and c-Kit(+) MC densities were significantly higher in SCCs than in ACs and control samples (P < .001). However, no significant difference was found when comparing tryptase(+) and c-Kit(+) MC densities between ACs and control samples (P values .185 and .516, respectively). MMP-9 was strongly expressed in SCCs and moderately expressed in ACs and control samples. A highly significant association was found between tryptase(+) MC density and the expression of MMP-9 (P < .001). The increase in MC density associated with the strong expression of MMP-9 may favor SCC progression. Copyright © 2011 Mosby, Inc. All rights reserved.

Different screening tests and milk somatic cell count for the prevalence of subclinical bovine mastitis in Bangladesh.

PubMed

Hoque, Md Nazmul; Das, Ziban Chandra; Talukder, Anup Kumar; Alam, Mohammad Shah; Rahman, Abu Nasar Md Aminoor

2015-01-01

Identification of cows with subclinical mastitis (SCM) is an important tool for sustainable dairying and implementing effective mastitis control strategies. A total of 892 quarters milk samples from 228 lactating cows were screened by California mastitis test (CMT), White side test (WST), Surf field mastitis test (SFMT), and somatic cell count (SCC) to study the prevalence of bovine SCM in some selected areas of Bangladesh. Out of 228 cows, 148 (64.9%), 138 (60.5%), 132 (57.9%), and 164 (71.9%) were found positive for SCM by CMT, WST, SFMT, and SCC, respectively. The prevalence of bovine SCM was diagnosed 45.7, 40.2, 36.6, and 29.6% in Chittagong, Sirajgonj, Mymensingh, and Gazipur districts, respectively, based on a combination of all tests. The overall quarter-wise prevalence of SCM was 45.7, 43.5, 41.2, and 55.0% for CMT, WST, SFMT, and SCC. Single quarters and left front quarters were more prone to SCM (P < 0.05). Friesian crossbred cows (56.4%), BCS 2.0-2.5 (55.4%), and parity 4-6 (52.4%), the late lactation stage (5-8 months; 64.7%) and high yielding cows (16-20 L/day; 65.3%) were more susceptible to SCM (P < 0.05). The sensitivity of the CMT, WST, SFMT, and SCC was 65.8, 57.9, 51.0, and 82.5%; specificity 76.2, 72.4, 69.5, and 89.4%; percentage accuracy 70.0, 64.8, 59.9, and 85.2%; positive predictive value 75.2, 69.8, 64.9, and 92.7%, respectively. The categories of CMT reactions were strongly correlated with SCC (P < 0.05). Kappa value of SCC was higher than that of other tests (SCC>CMT>WST>SFMT). Thus, CMT was concluded to be the most accurate (r = 0.782) field diagnostic test after laboratory test like SCC (r = 0.924). However, the use of any single test may not be reliable in diagnosing SCM, while the result of CMT supported by SCC might be used effectively to pinpoint diagnosis of SCM in dairy animals than alone.

Serum expression level of squamous cell carcinoma antigen, highly sensitive C-reactive protein, and CA-125 as potential biomarkers for recurrence of cervical cancer.

PubMed

Guo, Suyang; Yang, Bo; Liu, Hongli; Li, Yuzhi; Li, Shengze; Ma, Ling; Liu, Jian; Guo, Wei

2017-01-01

The aim of this study was to evaluate the serum expression levels of squamous cell carcinoma antigen (SCC-Ag), highly sensitive C-reactive protein (hs-CRP), and CA-125 as potential serum biomarkers for recurrence of cervical cancer. Eighty-six cervical cancer patients who received radical treatment were retrospectively included in this study from February 2011 to January 2014. Of the included 86 cases, 23 were recurred within the 36 months (recurrence group [RG]) and other 63 patients did not (non-RG [NRG]). The serum levels of SCC-Ag, hs-CRP, and CA-125 were examined and compared between the two groups. The prediction recurrence sensitivity, specificity area under the receiver operating characteristic curve were calculated by STATA11.0 software (http://www.stata.com). The correlation among SCC-Ag, hs-CRP, and CA-125 were analyzed by Pearson correlation test. The serum levels of SCC-Ag, hs-CRP, and CA-125 were 1.29 (0.21-33.20) mg/mL, 4.78 (0.22-175.20) mg/mL, and 11.56 (2.028-123.66) IU/mL for NRG and 5.64 (0.50-136.80) mg/mL, 22.41 (0.56-588.90) mg/mL, and 25.41 (3.658-3687.00) IU/mL for RG, respectively. The serum levels of SCC-Ag, hs-CRP, and CA-125 in NG group were significant higher than those of NRG group (P < 0.05). The recurrence prediction sensitivity was 0.74, 0.65, and 0.74; specificity was 0.65, 0.63, and 0.58; area under the curve was 0.75, 0.66, and 0.67, respectively, for serum SCC-Ag, hs-CRP, and CA-125. Significant positive correlation between SCC-Ag and hs-CRP (rpearson = 0.20, P = 0.04), SCC-Ag and CA-125 (rpearson = 0.64, P < 0.001), hs-CRP and CA-125 (rpearson= -0.13, P = 0.56) was found in the RG patients. Serum SCC-Ag, hs-CRP, and CA-125 were higher in recurrence cervical patients which could be potential biomarkers for predicting cervical cancer recurrence risk.

Hypoxia-Inducible Factor Pathway Inhibition Resolves Tumor Hypoxia and Improves Local Tumor Control After Single-Dose Irradiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Helbig, Linda; Department of Radiation Oncology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden; Koi, Lydia

2014-01-01

Purpose: To study the effects of BAY-84-7296, a novel orally bioavailable inhibitor of mitochondrial complex I and hypoxia-inducible factor 1 (HIF-1) activity, on hypoxia, microenvironment, and radiation response of tumors. Methods and Materials: UT-SCC-5 and UT-SCC-14 human squamous cell carcinomas were transplanted subcutaneously in nude mice. When tumors reached 4 mm in diameter BAY-84-7296 (Bayer Pharma AG) or carrier was daily administered to the animals. At 7 mm tumors were either excised for Western blot and immunohistologic investigations or were irradiated with single doses. After irradiation animals were randomized to receive BAY-84-7296 maintenance or carrier. Local tumor control was evaluatedmore » 150 days after irradiation, and the dose to control 50% of tumors (TCD{sub 50}) was calculated. Results: BAY-84-7296 decreased nuclear HIF-1α expression. Daily administration of inhibitor for approximately 2 weeks resulted in a marked decrease of pimonidazole hypoxic fraction in UT-SCC-5 (0.5% vs 21%, P<.0001) and in UT-SCC-14 (0.3% vs 19%, P<.0001). This decrease was accompanied by a significant increase in fraction of perfused vessels in UT-SCC-14 but not in UT-SCC-5. Bromodeoxyuridine and Ki67 labeling indices were significantly reduced only in UT-SCC-5. No significant changes were observed in vascular area or necrosis. BAY-84-7296 before single-dose irradiation significantly decreased TCD{sub 50}, with an enhancement ratio of 1.37 (95% confidence interval [CI] 1.13-1.72) in UT-SCC-5 and of 1.55 (95% CI 1.26-1.94) in UT-SCC-14. BAY-84-7296 maintenance after irradiation did not further decrease TCD{sub 50}. Conclusions: BAY-84-7296 resulted in a marked decrease in tumor hypoxia and substantially reduced radioresistance of tumor cells with the capacity to cause a local recurrence after irradiation. The data suggest that reduction of cellular hypoxia tolerance by BAY-84-7296 may represent the primary biological mechanism underlying the observed enhancement of radiation response. Whether this mechanism contributes to the improved outcome of fractionated chemoradiation therapy warrants further investigation.« less

Characterization of dendritic cells in lip and oral cavity squamous cell carcinoma.

PubMed

Costa, Nádia Lago; Gonçalves, Andréia Souza; Martins, Allisson Filipe Lopes; Arantes, Diego Antônio Costa; Silva, Tarcília Aparecida; Batista, Aline Carvalho

2016-07-01

There may be differences in the antitumor immunity induced by dendritic cells (DCs) during the development of squamous cell carcinoma (SCC) located in the lip rather than in the oral cavity. The aim of this study was to evaluate the number of immature and mature DCs in SCC and potentially malignant disorders of the oral cavity and lip. Immunohistochemistry was used to identify the number (cells/mm(2) ) of immature (CD1a(+) ) or mature (CD83(+) ) DCs in samples of oral cavity SCC (OCSCC) (n = 39), lip SCC (LSCC) (n = 23), leukoplakia (LK) (n = 21), actinic cheilitis (AC) (n = 13), and normal mucosa of the oral cavity (OC control, n = 12) and the lip (lip control, n = 11). The number of CD1a(+) cells tended to be higher in the OC control samples compared with the LK (P = 0.04) and OCSCC (P = 0.21). Unlike, this cell population was lower in the lip control than in AC or LSCC (P < 0.05). The number of CD83(+) cells was increased in the LSCC samples compared with the AC and lip control (P = 0.0001) and in OCSCC compared with both the LK (P = 0.001) and OC control (P = 0.0001) samples. LSCC showed an elevated number of CD1a(+) and CD83(+) cells compared with OCSCC (P = 0.03). The population of mature DCs was lower than the population of immature DCs in all of the tested groups (P < 0.05). There were a greater number of both mature and immature DC populations in the LSCC samples than in the OCSCC, which could contribute to establishing a more effective immune antitumor response for this neoplasm. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Diagnosis and Clinical Management of Human Papilloma Virus-Related Gingival Squamous Cell Carcinoma in a Patient With Leukemia: A Case Report.

PubMed

Yassin, Alaa; Dixon, Douglas R; Oda, Dolphine; London, Robert M

2016-02-01

Close clinical inspection for intraoral lesions in patients with leukemia that develop chronic graft-versus-host disease (cGVHD) is critical. Additionally, neoplasias developing in bone marrow transplant patients after treatment for leukemia represent a significant obstacle for long-term patient survival, necessitating lifetime follow-up by health care providers. This case report describes the identification, diagnosis, and treatment of gingival squamous cell carcinoma (SCC) in a patient with leukemia who was treated previously with a stem cell transplant and referred for routine periodontal care. A 53-year-old male was referred to the Department of Periodontics for an assessment of tooth #10 with 2+ mobility and associated cross-bite occlusion. The patient was diagnosed with acute myeloid leukemia at age 39 years, received hematopoietic stem cell transplantation (HSCT), and later developed cGVHD followed by human papilloma virus (HPV) infections. During the periodontal evaluation, a large, non-painful, exophytic, alveolar gingival mass was identified and later diagnosed as SCC. It is unusual that oral SCC presents as an exophytic, gingival swelling. The patient received comprehensive periodontal management in coordination with his otolaryngology team before and during the diagnosis of SCC secondary to cGVHD and HPV infection. Patients with a history of HSCT treatment for leukemia and subsequent cGVHD are at a high risk of developing second primary oral malignancies, including SCC. Exposure to oncogenic HPV infection may compound this risk. Therefore, it is important for dentists to be aware of special treatment concerns and to frequently screen these patients to achieve early diagnosis and treatment of these neoplasms.

Multimodal fluorescence molecular imaging for in vivo characterization of skin cancer using endogenous and exogenous fluorophores

NASA Astrophysics Data System (ADS)

Miller, Jessica P.; Habimana-Griffin, LeMoyne; Edwards, Tracy S.; Achilefu, Samuel

2017-06-01

Similarity of skin cancer with many benign skin pathologies requires reliable methods to detect and differentiate the different types of these lesions. Previous studies have explored the use of disparate optical techniques to identify and estimate the invasive nature of melanoma and basal cell carcinoma with varying outcomes. Here, we used a concerted approach that provides complementary information for rapid screening and characterization of tumors, focusing on squamous cell carcinoma (SCC) of the skin. Assessment of in vivo autofluorescence lifetime (FLT) imaging of endogenous fluorophores that are excitable at longer wavelengths (480 nm) than conventional NADH and FAD revealed a decrease in the short FLT component for SCC compared to normal skin, with mean values of 0.57±0.026 ns and 0.61±0.021 ns, respectively (p=0.004). Subsequent systemic administration of a near-infrared fluorescent molecular probe in SCC bearing mice, followed by the implementation of image processing methods on data acquired from two-dimensional and three-dimensional fluorescence molecular imaging, allowed us to estimate the tumor volume and depth, as well as quantify the fluorescent probe in the tumor. The result suggests the involvement of lipofuscin-like lipopigments and riboflavin in SCC metabolism and serves as a model for staging SCC.

Risk factors for squamous cell carcinoma of the penis--population-based case-control study in Denmark.

PubMed

Madsen, Birgitte Schütt; van den Brule, Adriaan J C; Jensen, Helle Lone; Wohlfahrt, Jan; Frisch, Morten

2008-10-01

Few etiologic studies of squamous cell carcinoma (SCC) of the penis have been carried out in populations where childhood circumcision is rare. A total of 71 patients with invasive (n=53) or in situ (n=18) penile SCC, 86 prostate cancer controls, and 103 population controls were interviewed in a population-based case-control study in Denmark. For 37 penile SCC patients, tissue samples were PCR examined for human papillomavirus (HPV) DNA. Overall, 65% of PCR-examined penile SCCs were high-risk HPV-positive, most of which (22 of 24; 92%) were due to HPV16. Penile SCC risk was positively associated with measures of early and high sexual activity, including lifetime number of female sex partners, number of female sex partners before age 20, age at first intercourse, penile-oral sex, a history of anogenital warts, and never having used condoms. Histories of phimosis and priapism at least 5 years before diagnosis were also significant risk factors, whereas alcohol abstinence was associated with reduced risk. Our study confirms sexually transmitted HPV16 infection and phimosis as major risk factors for penile SCC and suggests that penile-oral sex may be an important means of viral transmission. The association with priapism was unexpected and needs replication.

EB1 protein alteration characterizes sporadic but not ulcerative colitis associated colorectal cancer.

PubMed

Gemoll, Timo; Kollbeck, Sophie L; Karstens, Karl F; Hò, Gia G; Hartwig, Sonja; Strohkamp, Sarah; Schillo, Katharina; Thorns, Christoph; Oberländer, Martina; Kalies, Kathrin; Lehr, Stefan; Habermann, Jens K

2017-08-15

While carcinogenesis in Sporadic Colorectal Cancer (SCC) has been thoroughly studied, less is known about Ulcerative Colitis associated Colorectal Cancer (UCC). This study aimed to identify and validate differentially expressed proteins between clinical samples of SCC and UCC to elucidate new insights of UCC/SCC carcinogenesis and progression. Multiplex-fluorescence two-dimensional gel electrophoresis (2-D DIGE) and mass spectrometry identified 67 proteoforms representing 43 distinct proteins. After analysis by Ingenuity Pathway Analysis ® (IPA), subsequent Western blot validation proofed the differential expression of Heat shock 27 kDA protein 1 (HSPB1) and Microtubule-associated protein R/EB family, member 1 (EB1) while the latter one showed also expression differences by immunohistochemistry. Fresh frozen tissue of UCC ( n = 10) matched with SCC ( n = 10) was investigated. Proteins of cancerous intestinal mucosal cells were obtained by Laser Capture Microdissection (LCM) and compared by 2-D DIGE. Significant spots were identified by mass spectrometry. After IPA, three proteins [EB1, HSPB1, and Annexin 5 (ANXA5)] were chosen for further validation by Western blotting and tissue microarray-based immunohistochemistry. This study identified significant differences in protein expression of colorectal carcinoma cells from UCC patients compared to patients with SCC. Particularly, EB1 was validated in an independent clinical cohort.

Bulk tank somatic cell counts analyzed by statistical process control tools to identify and monitor subclinical mastitis incidence.

PubMed

Lukas, J M; Hawkins, D M; Kinsel, M L; Reneau, J K

2005-11-01

The objective of this study was to examine the relationship between monthly Dairy Herd Improvement (DHI) subclinical mastitis and new infection rate estimates and daily bulk tank somatic cell count (SCC) summarized by statistical process control tools. Dairy Herd Improvement Association test-day subclinical mastitis and new infection rate estimates along with daily or every other day bulk tank SCC data were collected for 12 mo of 2003 from 275 Upper Midwest dairy herds. Herds were divided into 5 herd production categories. A linear score [LNS = ln(BTSCC/100,000)/0.693147 + 3] was calculated for each individual bulk tank SCC. For both the raw SCC and the transformed data, the mean and sigma were calculated using the statistical quality control individual measurement and moving range chart procedure of Statistical Analysis System. One hundred eighty-three herds of the 275 herds from the study data set were then randomly selected and the raw (method 1) and transformed (method 2) bulk tank SCC mean and sigma were used to develop models for predicting subclinical mastitis and new infection rate estimates. Herd production category was also included in all models as 5 dummy variables. Models were validated by calculating estimates of subclinical mastitis and new infection rates for the remaining 92 herds and plotting them against observed values of each of the dependents. Only herd production category and bulk tank SCC mean were significant and remained in the final models. High R2 values (0.83 and 0.81 for methods 1 and 2, respectively) indicated a strong correlation between the bulk tank SCC and herd's subclinical mastitis prevalence. The standard errors of the estimate were 4.02 and 4.28% for methods 1 and 2, respectively, and decreased with increasing herd production. As a case study, Shewhart Individual Measurement Charts were plotted from the bulk tank SCC to identify shifts in mastitis incidence. Four of 5 charts examined signaled a change in bulk tank SCC before the DHI test day identified the change in subclinical mastitis prevalence. It can be concluded that applying statistical process control tools to daily bulk tank SCC can be used to estimate subclinical mastitis prevalence in the herd and observe for change in the subclinical mastitis status. Single DHI test day estimates of new infection rate were insufficient to accurately describe its dynamics.

Varied clinical presentations of seven patients with mutations in CYP11A1 encoding the cholesterol side-chain cleavage enzyme, P450scc.

PubMed

Tee, Meng Kian; Abramsohn, Michal; Loewenthal, Neta; Harris, Mark; Siwach, Sudeep; Kaplinsky, Ana; Markus, Barak; Birk, Ohad; Sheffield, Val C; Parvari, Ruti; Pavari, Ruti; Hershkovitz, Eli; Miller, Walter L

2013-02-01

The cholesterol side-chain cleavage enzyme P450scc, encoded by CYP11A1, converts cholesterol to pregnenolone to initiate steroidogenesis. P450scc deficiency can disrupt adrenal and gonadal steroidogenesis, resembling congenital lipoid adrenal hyperplasia clinically and hormonally; only 12 such patients have been reported previously. We sought to expand clinical and genetic experience with P450scc deficiency. We sequenced candidate genes in 7 children with adrenal insufficiency who lacked disordered sexual development. P450scc missense mutations were recreated in the F2 vector, which expresses the fusion protein P450scc-Ferredoxin Reductase-Ferredoxin. COS-1 cells were transfected, production of pregnenolone was assayed, and apparent kinetic parameters were calculated. Previously described P450scc mutants were assayed in parallel. Four of five Bedouin children in one kindred were compound heterozygotes for mutations c.694C>T (Arg232Stop) and c.644T>C (Phe215Ser). Single-nucleotide polymorphism analysis confirmed segregation of these mutations. The fifth kindred member and another Bedouin patient presented in infancy and were homozygous for Arg232Stop. A patient from Fiji presenting in infancy was homozygous for c.358T>C (Arg120Stop). All mutations are novel. As assayed in the F2 fusion protein, P450scc Phe215Ser retained 2.5% of wild-type activity; previously described mutants Leu141Trp and Ala269Val had 2.6% and 12% of wild-type activity, respectively, and Val415Glu and c.835delA lacked detectable activity. Although P450scc is required to produce placental progesterone required to maintain pregnancy, severe mutations in P450scc are compatible with term gestation; milder P450scc mutations may present later without disordered sexual development. Enlarged adrenals usually distinguish steroidogenic acute regulatory protein deficiency from P450scc deficiency, but only DNA sequencing is definitive.

Overexpression of TMPRSS4 in non-small cell lung cancer is associated with poor prognosis in patients with squamous histology

PubMed Central

Larzabal, L; Nguewa, P A; Pio, R; Blanco, D; Sanchez, B; Rodríguez, M J; Pajares, M J; Catena, R; Montuenga, L M; Calvo, A

2011-01-01

Background: Mortality rates in lung cancer patients have not decreased significantly in recent years, even with the implementation of new therapeutic regimens. One of the main problems is that a large proportion of patients present local or distant metastasis at the time of diagnosis. The need for identification of novel biomarkers and therapeutic targets for a more effective management of lung cancer led us to investigate TMPRSS4, a protease reported to promote tumour growth and metastasis. Material and methods: In all, 34 lung cancer cell lines were used to evaluate the TMPRSS4 expression. Cell migration and clonogenic assays, and an in-vivo lung metastasis model were used for functional analysis of the TMPRSS4 downregulation in H358, H441 and H2170 cell lines. The TMPRSS4 expression analysis in normal and malignant lung tissue samples was performed by qPCR. Five different microarray-based publicly available expression databases were used to validate our results and to study prognosis. Results: The TMPRSS4 knock down in H358, H441 and H2170 cells resulted in a significant reduction in proliferation, clonogenic capacity and invasion. A significant (P<0.05) decrease in the lung colonisation and growth was found when mice were injected with TMPRSS4-depleated H358-derived clones, as compared with controls. Expression of TMPRSS4 showed a >30-fold increase (P<0.001) in tumours in comparison with non-malignant samples. Levels in tumours with squamous cell carcinoma (SCC) histology were found to be significantly higher (P<0.001) than those with adenocarcinoma (AC) histology, which was confirmed in data retrieved from the microarrays. Kaplan–Meier curves demonstrated that high levels of TMPRSS4 were significantly associated (P=0.017) with reduced overall survival in the patients with SCC histology, whereas no correlation was found for the AC histology. Conclusion: Our results demonstrate that TMPRSS4 has a role in the lung cancer development. The potential use of TMPRSS4 as a biomarker for lung cancer detection or as a predictor of patient's outcome warrants further investigation. PMID:22067904

Udder health of dairy cows fed different dietary energy levels after a short or no dry period without use of dry cow antibiotics.

PubMed

van Hoeij, R J; Lam, T J G M; Bruckmaier, R M; Dijkstra, J; Remmelink, G J; Kemp, B; van Knegsel, A T M

2018-05-01

Reports on the effects of length of dry period (DP) on udder health of cows that were not treated with dry cow antibiotics are scarce. Additionally, the effects of a reduced dietary energy level for cows with a 0-d DP on udder health have not yet been studied. The aims of this study were (1) to compare effects of a 0-d or 30-d DP without use of dry cow antibiotics on udder health across the DP and subsequent lactation in dairy cows fed different dietary energy levels and (2) to evaluate associations between udder health and metabolic status of dairy cows. Five weeks before the expected calving date, Holstein-Friesian dairy cows (n = 115) were blocked for parity, expected calving date, and milk yield and somatic cell count (SCC) at their 2 last test days and were randomly assigned to 2 DP lengths: 0-d DP (n = 77) or 30-d DP (n = 38). Quarter milk samples were taken in wk 5 prepartum and in wk 1 and 5 postpartum. Proportion of quarters with elevated SCC (SCC ≥200,000 cells/mL) and proportion of udder pathogens in quarter milk samples did not differ between DP lengths among weeks. After calving, 102 of these cows were randomly assigned to 3 treatments: a 30-d DP with a standard energy level required for expected milk yield (30-d DP SEL; n = 36), a 0-d DP with the same energy level as cows with a 30-d DP (0-d DP SEL; n = 33), and a 0-d DP with a low energy level (0-d DP LEL, n = 33). From wk 8 of lactation onward, cows received either a glucogenic ration consisting of corn silage and grass silage or a lipogenic ration consisting of grass silage and sugar beet pulp at a standard or low energy level. During wk 1 to 7 postpartum, treatment did not affect SCC or SCC corrected for milk yield. During wk 8 to 44 of lactation, 0-d DP SEL cows had a greater SCC than 0-d DP LEL or 30-d DP SEL cows and had a greater SCC corrected for milk yield than 0-d DP LEL cows. During wk 1 to 44 of lactation, occurrence of at least 1 elevation of SCC (SCC ≥200,000 cells/mL after 2 wk of SCC <200,000 cells/mL) was not different among treatments. The 0-d DP SEL cows but not the 0-d DP LEL cows tended to have a 2.17 times greater hazard of having a case of clinical mastitis at any time in lactation than 30-d DP SEL cows. In wk 1 to 44 of lactation, lower fat- and protein- corrected milk yield and energy intake, greater energy balance, and greater plasma insulin concentration were associated with greater SCC. In conclusion, DP length did not affect udder health in the DP and in early lactation but seemed to decrease udder health for 0-d DP SEL cows in later lactation compared with 30-d DP SEL or 0-d DP LEL cows. Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Epigenetic Inactivation of GALR1 in Head and Neck Cancer

PubMed Central

Misawa, Kiyoshi; Ueda, Yo; Kanazawa, Takeharu; Misawa, Yuki; Jang, Ilwhan; Brenner, John Chadwick; Ogawa, Tetsuya; Takebayashi, Satoru; Grenman, Reidar A.; Herman, James G.; Mineta, Hiroyuki; Carey, Thomas E.

2011-01-01

Purpose One copy of the GALR1 locus on 18q is often deleted and expression is absent in some head and neck squamous cell carcinoma (HNSCC) cell lines. To determine if LOH and hypermethylation might silence the GALR1 gene, promoter methylation status and gene expression were assessed in a large panel of HNSCC cell lines and tumors. Experimental Design Promoter methylation of GALR1 in 72 cell lines and 100 primary tumor samples was analyzed using methylation-specific PCR (MSP). GALR1 expression and methylation status were analyzed further by real-time PCR and bisulfite sequencing analysis. Results The GALR1 promoter was fully or partially methylated in 38 of 72 HNSCC cell lines (52.7%) but not in the majority 18/20 (90.0%) of non-malignant lines. GALR1 methylation was also found in 38/100 (38%) primary tumor specimens. Methylation correlated with decreased GALR1 expression. In tumors methylation was significantly correlated with increased tumor size (P=0.0036), lymph-node status (P=0.0414), tumor stage (P=0.0037), cyclin D1 expression (P=0.0420), and p16 methylation (P=0.0494) and survival (P=0.045). Bisulfite sequencing of 36 CpG sites upstream of the transcription start site revealed that CpG methylation within transcription factor binding sites correlated with complete suppression of GALR1 mRNA. Treatment with TSA and 5-azacytidine restored GALR1 expression. In UM-SCC-23 cells that have total silencing of GALR1, exogenous GALR1 expression and stimulation with galanin suppressed cell proliferation. Conclusions Frequent promoter hypermethylation, gene silencing, association with prognosis, and growth suppression after re-expression support the hypothesis that GALR1 is a tumor suppressor gene in HNSCC. PMID:19047085

Analysis of stress corrosion cracking in alloy 718 following commercial reactor exposure

DOE PAGES

Leonard, Keith J.; Gussev, Maxim N.; Stevens, Jacqueline N.; ...

2015-08-24

Alloy 718 is generally considered a highly corrosion-resistant material but can still be susceptible to stress corrosion cracking (SCC). The combination of factors leading to SCC susceptibility in the alloy is not always clear enough. In this paper, alloy 718 leaf spring (LS) materials that suffered stress corrosion damage during two 24-month cycles in pressurized water reactor service, operated to >45 MWd/mtU burn-up, was investigated. Compared to archival samples fabricated through the same processing conditions, little microstructural and property changes occurred in the material with in-service irradiation, contrary to high dose rate laboratory-based experiments reported in literature. Though the lackmore » of delta phase formation along grain boundaries would suggest a more SCC resistant microstructure, grain boundary cracking in the material was extensive. Crack propagation routes were explored through focused ion beam milling of specimens near the crack tip for transmission electron microscopy as well as in polished plan view and cross-sectional samples for electron backscatter diffraction analysis. It has been shown in this study that cracks propagated mainly along random high-angle grain boundaries, with the material around cracks displaying a high local density of dislocations. The slip lines were produced through the local deformation of the leaf spring material above their yield strength. Also, the cause for local SCC appears to be related to oxidation of both slip lines and grain boundaries, which under the high in-service stresses resulted in crack development in the material.« less

Pseudocarcinomatous hyperplasia in anaplastic large cell lymphoma, a mimicker of poorly differentiated squamous cell carcinoma: report of a case and review of the literature.

PubMed

Price, Alexandra; Miller, Jason H; Junkins-Hopkins, Jacqueline M

2015-11-01

Pseudocarcinomatous hyperplasia can occasionally be observed in biopsies of CD30-positive lymphoproliferative disorders. It is important to be cognizant of this association, because epithelial hyperproliferation can overshadow large atypical lymphoid cells, leading to an erroneous diagnosis of squamous cell carcinoma (SCC) or keratoacanthoma. Herein, we present a case of anaplastic large cell lymphoma (ALCL) with pseudocarcinomatous hyperplasia simulating a poorly differentiated carcinoma and review the literature on this subject. Immunohistochemical staining with p63 helped delineate the infiltrating tongues of pseudocarcinomatous hyperplasia from the malignant infiltrate. We present this case to raise awareness of the potential for pseudocarcinomatous hyperplasia to occur in the setting of CD30+ lymphoproliferative disorders. Clinicians and dermatopathologists should consider the possibility of ALCL or lymphomatoid papulosis when examining lesions with features of inflamed SCC, especially if the tumor presents on a site or in a patient that is not typical of SCC. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A genome-wide screen identifies YAP/WBP2 interplay conferring growth advantage on human epidermal stem cells

PubMed Central

Walko, Gernot; Woodhouse, Samuel; Pisco, Angela Oliveira; Rognoni, Emanuel; Liakath-Ali, Kifayathullah; Lichtenberger, Beate M.; Mishra, Ajay; Telerman, Stephanie B.; Viswanathan, Priyalakshmi; Logtenberg, Meike; Renz, Lisa M.; Donati, Giacomo; Quist, Sven R.; Watt, Fiona M.

2017-01-01

Individual human epidermal cells differ in their self-renewal ability. To uncover the molecular basis for this heterogeneity, we performed genome-wide pooled RNA interference screens and identified genes conferring a clonal growth advantage on normal and neoplastic (cutaneous squamous cell carcinoma, cSCC) human epidermal cells. The Hippo effector YAP was amongst the top positive growth regulators in both screens. By integrating the Hippo network interactome with our data sets, we identify WW-binding protein 2 (WBP2) as an important co-factor of YAP that enhances YAP/TEAD-mediated gene transcription. YAP and WPB2 are upregulated in actively proliferating cells of mouse and human epidermis and cSCC, and downregulated during terminal differentiation. WBP2 deletion in mouse skin results in reduced proliferation in neonatal and wounded adult epidermis. In reconstituted epidermis YAP/WBP2 activity is controlled by intercellular adhesion rather than canonical Hippo signalling. We propose that defective intercellular adhesion contributes to uncontrolled cSCC growth by preventing inhibition of YAP/WBP2. PMID:28332498

Desmoglein 2 modulates extracellular vesicle release from squamous cell carcinoma keratinocytes.

PubMed

Overmiller, Andrew M; Pierluissi, Jennifer A; Wermuth, Peter J; Sauma, Sami; Martinez-Outschoorn, Ubaldo; Tuluc, Madalina; Luginbuhl, Adam; Curry, Joseph; Harshyne, Larry A; Wahl, James K; South, Andrew P; Mahoney, Mỹ G

2017-08-01

Extracellular vesicles (EVs) are nanoscale membrane-derived vesicles that serve as intercellular messengers carrying lipids, proteins, and genetic material. Substantial evidence has shown that cancer-derived EVs, secreted by tumor cells into the blood and other bodily fluids, play a critical role in modulating the tumor microenvironment and affecting the pathogenesis of cancer. Here we demonstrate for the first time that squamous cell carcinoma (SCC) EVs were enriched with the C-terminal fragment of desmoglein 2 (Dsg2), a desmosomal cadherin often overexpressed in malignancies. Overexpression of Dsg2 increased EV release and mitogenic content including epidermal growth factor receptor and c-Src. Inhibiting ectodomain shedding of Dsg2 with the matrix metalloproteinase inhibitor GM6001 resulted in accumulation of full-length Dsg2 in EVs and reduced EV release. When cocultured with Dsg2/green fluorescence protein-expressing SCC cells, green fluorescence protein signal was detected by fluorescence-activated cell sorting analysis in the CD90 + fibroblasts. Furthermore, SCC EVs activated Erk1/2 and Akt signaling and enhanced fibroblast cell proliferation. In vivo, Dsg2 was highly up-regulated in the head and neck SCCs, and EVs isolated from sera of patients with SCC were enriched in Dsg2 C-terminal fragment and epidermal growth factor receptor. This study defines a mechanism by which Dsg2 expression in cancer cells can modulate the tumor microenvironment, a step critical for tumor progression.-Overmiller, A. M., Pierluissi, J. A., Wermuth, P. J., Sauma, S., Martinez-Outschoorn, U., Tuluc, M., Luginbuhl, A., Curry, J., Harshyne, L. A., Wahl, J. K. III, South, A. P., Mahoney, M. G. Desmoglein 2 modulates extracellular vesicle release from squamous cell carcinoma keratinocytes. © FASEB.

Associations of dairy cow behavior, barn hygiene, cow hygiene, and risk of elevated somatic cell count.

PubMed

Devries, T J; Aarnoudse, M G; Barkema, H W; Leslie, K E; von Keyserlingk, M A G

2012-10-01

Poor dairy cow hygiene has been consistently associated with elevated somatic cell count (SCC) and the risk of subclinical mastitis. The objective of this study was to determine the associations between dairy cow standing and lying behavior, barn hygiene, cow hygiene, and the risk of experiencing elevated SCC. Lactating Holstein dairy cows (n=69; 86 ± 51 DIM; parity: 2.0 ± 1.2; means ± SD), kept in 1 of 2 groups, were monitored over a 4-mo period. Each group contained 61 ± 1 (mean ± SD) cows over the study period; complete data were obtained from 37 and 32 animals within each respective group. Cows were housed in a sand-bedded, freestall barn with 2 symmetrical pens, each with a free cow traffic automatic milking system. To vary barn hygiene, in 4 consecutive 28-d periods, alley manure scrapers in each of the 2 pens were randomly assigned to frequencies of operation of 3, 6, 12, and 24 times per day. During the last 7 d of each period, cow hygiene (upper leg/flank, lower legs, and udder; scale of 1 = very clean to 4 = very dirty) and stall hygiene (number of 0.15×0.15-m squares contaminated with manure in a 1.20×1.65-m grid) were recorded. Standing and lying behavior of the cows were collected during those days using data loggers. Individual-cow SCC was recorded at the beginning and end of each 28-d period. Elevated SCC was used as an indicator of subclinical mastitis; incidence of elevated SCC was defined as having a SCC >200,000 cells/mL at the end of each 28-d period, when SCC was <100,000 cells/mL at the beginning of the period. Less frequent scraping of the barn alleys was associated with cows having poorer hygiene. Poor udder hygiene was associated with poor stall hygiene. Longer lying duration was associated with poor hygiene of the upper legs/flank and udder. Greater premilking standing duration was associated with poor udder hygiene and decreased frequency of lying bouts was associated with poor hygiene of the lower legs. Higher milk yield was associated with poor hygiene of the udder and lower legs; multiparous cows had poorer hygiene of the upper legs/flank and udder. Over the study period, 24 new cases of elevated SCC were detected. No associations existed for the risk of experiencing an elevated SCC with alley scraping frequency or cow behavior patterns. However, increased odds of occurrence of elevated SCC were noted for cows of lower milk yield as well as for multiparous cows. In summary, these results show that cow hygiene is affected by the standing and lying behavior of cows and by the cleanliness of the cow's environment. These findings emphasize the need for cows to be provided clean standing and lying environments. The results also show that frequent cleaning of barn alley floors will help improve cow hygiene. Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Association between isolation of Staphylococcus aureus one week after calving and milk yield, somatic cell count, clinical mastitis, and culling through the remaining lactation.

PubMed

Whist, Anne Cathrine; Osterås, Olav; Sølverød, Liv

2009-02-01

Cows with isolation of Staphylococcus aureus approximately 1 week after calving and milk yield, somatic cell count (SCC), clinical mastitis (CM), and culling risk through the remaining lactation were assessed in 178 Norwegian dairy herds. Mixed models with repeated measures were used to compare milk yield and SCC, and survival analyses were used to estimate the hazard ratio for CM and culling. On average, cows with an isolate of Staph. aureus had a significantly higher SCC than culture-negative cows. If no post-milking teat disinfection (PMTD) was used, the mean values of SCC were 42,000, 61,000, 68,000 and 77,000 cells/ml for cows with no Staph. aureus isolate, with Staph. aureus isolated in 1 quarter, in 2 quarters and more than 2 quarters respectively. If iodine PMTD was used, SCC means were 36,000; 63,000; 70,000 and 122,000, respectively. Primiparous cows testing positive for Staph. aureus had the same milk yield curve as culture-negative cows, except for those with Staph. aureus isolated in more than 2 quarters. They produced 229 kg less during a 305-d lactation. Multiparous cows with isolation of Staph. aureus in at least 1 quarter produced 94-161 kg less milk in 2nd and >3rd parity, respectively, and those with isolation in more than 2 quarters produced 303-390 kg less than multiparous culture-negative animals during a 305-d lactation. Compared with culture-negative cows, the hazard ratio for CM and culling in cows with isolation of Staph. aureus in at least 1 quarter was 2.0 (1.6-2.4) and 1.7 (1.5-1.9), respectively. There was a decrease in the SCC and in the CM risk in culture-negative cows where iodine PMTD had been used, indicating that iodine PMTD has a preventive effect on already healthy cows. For cows testing positive for Staph. aureus in more than 2 quarters at calving, iodine PMTD had a negative effect on the CM risk and on the SCC through the remaining lactation.

Association between somatic cell count after first parturition and cumulative milk yield in dairy cows.

PubMed

Archer, S C; Mc Coy, F; Wapenaar, W; Green, M J

2013-10-05

The aim was to assess the association between the somatic cell count of parity 1 cows between 5 and 30 days in milk (SCC1), and subsequent cumulative milk yield over approximately two years for cows in English and Welsh dairy herds. The dataset included records from 43,461 cows in 2111 herds, from 2004 to 2006. Cumulative milk yield was the model outcome, and a random effect was included to account for variation between herds. The model fitted the data well and was used to make predictions of cumulative milk yield, based on SCC1. A unit increase in the natural logarithm of SCC1/1000 was associated with a median decrease in cumulative milk yield of 482 kg, over a median study period of 868 days.

Synchronous metastatic adenoid cystic and squamous cell carcinoma of the cervical lymph nodes 31 years after ablation of the primary palatal tumour.

PubMed

Doumas, Stergios; Barrett, Andrew W; Carrillo, Mauricio; Tighe, John V

2013-10-01

The coexistence of different types of malignancy in cervical lymph nodes has been reported previously. We report the first case, to the best of our knowledge, of concurrent metastatic adenoid cystic carcinoma and squamous cell carcinoma (SCC) in cervical lymph nodes. A primary SCC developed three decades after treatment for adenoid cystic carcinoma of the palate, and the synchronous metastases became clinically apparent the following year. The aetiology of the SCC may have been related to radiotherapy or smoking. Whether the adenoid cystic carcinoma would have remained dormant, or was reactivated after perturbation of host defence mechanisms, is not known. Copyright © 2012 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

5-epi-Sinuleptolide induces cell cycle arrest and apoptosis through tumor necrosis factor/mitochondria-mediated caspase signaling pathway in human skin cancer cells.

PubMed

Liang, Chia-Hua; Wang, Guey-Horng; Chou, Tzung-Han; Wang, Shih-Hao; Lin, Rong-Jyh; Chan, Leong-Perng; So, Edmund Cheung; Sheu, Jyh-Horng

2012-07-01

Skin cancers are reportedly increasing worldwide. Developing novel anti-skin cancer drugs with minimal side effects is necessary to address this public health issue. Sinuleptolide has been demonstrated to possess anti-cancer cell activities; however, the mechanisms underlying the anti-skin cancer effects of 5-epi-sinuleptolide and sinuleptolide remain poorly understood. Apoptosis cell, cell-cycle-related regulatory factors, and mitochondria- and death receptor-dependent caspase pathway in 5-epi-sinuleptolide-induced cell apoptosis were examined using SCC25 cells. 5-epi-Sinuleptolide inhibited human skin cancer cell growth more than did sinuleptolide. Treatment of SCC25 cells with 5-epi-sinuleptolide increased apoptotic body formation, and induced cell-cycle arrest during the G2/M phase. Notably, 5-epi-sinuleptolide up-regulated p53 and p21 expression and inhibited G2/M phase regulators of cyclin B1 and cyclin-dependent kinease 1 (CDK1) in SCC25 cells. Additionally, 5-epi-sinuleptolide induced apoptosis by mitochondria-mediated cytochrome c and Bax up-expression, down-regulated Bcl-2, and activated caspase-9 and -3. 5-epi-Sinuleptolide also up-regulated tBid, which is associated with up-regulation of tumor necrosis factor-α (TNF-α) and Fas ligand (FasL) and their cognate receptors (i.e., TNF-RI, TNF-R2 and Fas), downstream adaptor TNF-R1-associated death domain (TRADD) and Fas-associated death domain (FADD), and activated caspase-8 in SCC25 cells. The analytical results indicate that the death receptor- and mitochondria-mediated caspase pathway is critical in 5-epi-sinuleptolide-induced apoptosis of skin cancer cells. This is the first report suggesting that the apoptosis mediates the anti-tumor effect of 5-epi-sinuleptolide. The results of this study might provide useful suggestions for designing of anti-tumor drugs for skin cancer patients. Copyright © 2012 Elsevier B.V. All rights reserved.

A comparison of the effect of short-acting and long-acting cloxacillin-based dry-cow therapy on somatic cell counts after calving in cows also given internal teat sealants.

PubMed

Whitfield, L K; Laven, R A

2018-01-01

To compare, in cows treated with an internal teat sealant, the effect of short-acting and long-acting cloxacillin-based dry-cow therapy on somatic cell counts (SCC) after calving. Cows from a spring-calving, pasture-based dairy farm in the Manawatu-Whanganui region of New Zealand were randomly allocated to receive either a short-acting cloxacillin and ampicillin dry-cow therapy and internal teat sealant (n=291) or a long-acting cloxacillin and ampicillin dry-cow therapy and internal teat sealant (n=288) at the end of lactation. Cows were managed on-farm with routine husbandry procedures through the dry period and following calving. A multivariable logistic regression model was used to determine the association between length of action of dry-cow therapy and the proportion of cows with a SCC >150,000 cells/mL at the first herd test after calving. Age of cow, mean SCC for the preceding season and interval from calving to the first post-calving herd test were all associated with the proportion of cows with an individual SCC >150,000 cells/mL at the first herd test (p<0.001) Treatment with the short-acting dry-cow therapy was not associated with decreased odds of cows having a SCC >150,000 cells/mL at the first herd test compared with treatment with long-acting dry-cow therapy (OR=0.724; 95% CI=0.40-1.30). In this herd, which routinely used internal teat sealants, the use of short-acting cloxacillin-based dry-cow therapy did not result in an increased proportion of cows with elevated SSC post-calving. This was a single farm, single year study but indicates that in this herd, changing from a long-acting to a short-acting antimicrobial may have no impact on the prevalence of subclinical mastitis.

[Epidemiology of occupational skin cancer due to UV-irradiation].

PubMed

Diepgen, T L; Drexler, H; Schmitt, J

2012-10-01

Skin cancer induced by occupational UV-irradiation is not an official occupational disease number in the appendix of the German ordinance on occupational diseases (Berufskrankheitenverordnung (BKV) but can be recognized as a "virtually" occupational disease according to § 9 (2) of the 7th book of the German Social Code (SGB VII). Epidemiological studies have demonstrated a positive, statistically significant and relevant association between occupational UV-irradiation and the risk of squamous cell carcinoma (SCC) and actinic keratoses (AK). Outdoor workers have on average a 100% higher risk to develop SCC compared to the general population. Therefore, the prerequisites for a new occupational disease are fulfilled and SCC and AK should be reported as an occupational disease if an additional 40% occupationally-related UV-irradiation is documented and the clinical criteria are typical for work- related skin cancer. Epidemiologic evidence also indicates a significant association between work-related UV-irradiation and basal cell carcinoma (BCC) risk: however the results are less consistent and the association is weaker than with SCC. There is an urgent need for further studies in outdoor workers on BCC and lentigo maligna melanoma.

Surgical management for squamous cell carcinoma of vulva.

PubMed

Amavi, Ayi Kossigan; Kouadio, Laurent; Adabra, Komlan; Tengue, Kodjo; Tijami, Fouad; Jalil, Abdelouahed

2016-01-01

To analyze our surgical management and the result of squamous cell carcinoma (SCC) of vulva. Retrospectively, we collected 38 cases of SCC; 17 cases of them were early SCC and 21 cases were locally advanced. The patients underwent primary surgery. The survival was estimated using Kaplan-Meier analysis and the log rank test. The mean age was 60.78 years. Total vulvectomy was performed in all patients. Superficial and deep incision of bilateral inguinal lymphadenectomy was performed by separates incisions for SCC infiltrating more than 1mm. The average tumor size was 53 mm (10 to 140mm). Morbidity was 42.1%. Lateral resection margin ≥8mm was obtained in 57.1%. Eighteen patients benefited from adjuvant radiotherapy. The follow-up median was 19.4 months (6 to 61.5 month) with 05 recurrences in 12 months. The survival using the Kaplan-Meyer analysis at 5 years, was 62.1% (71.2%N(-) vs 46.7%N(+); p = 0.13). We identified two groups for locally advanced vulva cancer. Primary surgery keeps its place. Neo adjuvant radio chemotherapy followed by surgery is the alternative treatment for locally extensive lesions.

Use of a staphylococcal vaccine to reduce prevalence of mastitis and lower somatic cell counts in a registered Saanen dairy goat herd.

PubMed

Kautz, F M; Nickerson, S C; Ely, L O

2014-08-01

This investigation evaluated the efficacy of a bacterin in reducing the prevalence of staphylococcal mastitis and somatic cell counts (SCC) in a dairy goat herd. Does were vaccinated or left as controls, and the levels of mastitis and SCC monitored over 18 months. Staphylococcus caprae (42.5%), S. xylosus (15.1%), and S. simulans (10.0%) were the predominant causes of intramammary infections (IMI). The infection rate was 1.64 IMI/doe among vaccinates, which tended to be lower (P < 0.12) than controls (2.67 IMI/doe). The spontaneous cure rate of IMI after immunization was 1.28 cures/doe in vaccinates, which was higher than controls (0.6 cures/doe; P < 0.043). Average SCC of milk samples from vaccinates tended to be lower than that of controls (1274 × 10(3)/ml vs. 1529 × 10(3)/ml, respectively) (P < 0.10). Results support the continued study of mastitis vaccines for use in managing staphylococcal mastitis and SCC in dairy goats. Published by Elsevier Ltd.

Ineffectiveness of the presence of H-ras/p53 combination of mutations in squamous cell carcinoma cells to induce a conversion of a nontumorigenic to a tumorigenic phenotype.

PubMed

Lee, H; Li, D; Prior, T; Casto, B C; Weghorst, C M; Shuler, C F; Milo, G E

1997-10-01

Human tumor cells have properties in vitro or in surrogate hosts that are distinct from those of normal cells, such as immortality, anchorage independence, and tumor formation in nude mice. However, different cells from individual tumors may exhibit some, but not all of these features. In previous years, human tumor cell lines derived from different tumor and tissue types have been studied to determine those molecular changes that are associated with the in vitro properties listed above and with tumorigenicity in nude mice. In the present study, seven cell lines derived from human tumors were characterized for p53 and ras mutations that may occur in SCC tumor phenotypes and for tumor formation in nude mice. This investigation was designed to examine whether co-occurrence of mutated ras and p53 lead to a malignant stage in the progression process. None of the seven cell lines contained mutations in the recognized "hot spots" of the p53 tumor suppressor gene, but four had a nonsense/splice mutation in codon 126 and a mutation in codon 12 of the H-ras gene. The remaining three cell lines had p53 mutations in intron 5, in codon 193, and a missense mutation in codon 126, respectively. Four of seven cell lines were nontumorigenic; two of these cell lines contained a nonsense p53-126 mutation and mutated ras; one had a missense mutation at codon 126 but no mutated ras; the the fourth had only a p53 mutation at codon 193. Two of the nontumorigenic cell lines were converted to tumorigenicity after treatment with methyl methanesulfonate or N-methyl-N'-nitro-N-nitrosoguanidine with no apparent additional mutations in either gene. Our analysis revealed that there was a high frequency of genetic diversity and mutations in both p53 and H-ras. There was also a lack of a causal relationship in the presence of mutations in p53 and the cells' ability to exhibit a malignant potential in nude mice.

Exploratory studies on some electrochemical cell systems

NASA Astrophysics Data System (ADS)

Chaudhuri, Srikumar; Guha, D.

Exploratory studies were conducted on cell systems with different metal anodes, and iodine and sulphur mixed with graphite powder in a polymer matrix as cathodes, using different electrolytes in non-aqueous and aqueous media as ionic charge carriers. The electrical conductance of the electrolyte solutions in aqueous and non-aqueous solvents, the open circuit voltage (OCV) and short circuit current (SCC) for the different cell systems were measured. To date, the non-aqueous solvents used in our studies were dimethylformamide, formamide, dioxan, and nitrobenzene, and the electrolytes used were potassium iodide, caustic potash, cetyltrimethylammonium bromide (CTAB), sodium lauryl sulphate (SLS) and calcium chloride. These electrolytes were used in both non-aqueous and aqueous media. In general, aqueous electrolyte solutions gave a better performance than non-aqueous electrolyte solutions. Of the aqueous electrolytes, the highest conductance was shown by potassium chloride solution in water (conductance=0.0334 mho). However, the best OCV and SCC were shown by aluminium as anode and iodine as cathode with a saturated solution of caustic potash in water. The OCV was 1.85 V and the SCC was 290 mA cm -2. The highest conductance among the non-aqueous systems was shown by caustic potash in formamide. (Conductance=0.013 mho.) The best OCV and SCC, however, were shown by a zinc anode and iodine cathode with saturated potassium chloride in formamide, having an OCV of 1.55 V and an SCC of 150 mA cm -2. Further studies are in progress to obtain detailed performance data and recharging characteristics of some of the more promising systems reported here.

Cutaway line drawing of STS-34 middeck experiment Polymer Morphology (PM)

NASA Technical Reports Server (NTRS)

1989-01-01

Cutaway line drawing shows components of STS-34 middeck experiment Polymer Morphology (PM). Generic Electronics Module (GEM) components include the control housing, circulating fans, hard disk, tape drives, computer boards, and heat exchanger. PM, a 3M-developed organic materials processing experiment, is designed to explore the effects of microgravity on polymeric materials as they are processed in space. The samples of polymeric materials being studied in the PM experiment are thin films (25 microns or less) approximately 25mm in diameter. The samples are mounted between two infrared transparent windows in a specially designed infrared cell that provides the capability of thermally processing the samples to 200 degrees Celsius with a high degree of thermal control. The samples are mounted on a carousel that allows them to be positioned, one at a time, in the infrared beam where spectra may be acquired. The GEM provides all carousel and sample cell control (SCC). The first flight of P

The LSH/HELLS homolog Irc5 contributes to cohesin association with chromatin in yeast.

PubMed

Litwin, Ireneusz; Bakowski, Tomasz; Maciaszczyk-Dziubinska, Ewa; Wysocki, Robert

2017-06-20

Accurate chromosome segregation is essential for every living cell as unequal distribution of chromosomes during cell division may result in genome instability that manifests in carcinogenesis and developmental disorders. Irc5 from Saccharomyces cerevisiae is a member of the conserved Snf2 family of ATP-dependent DNA translocases and its function is poorly understood. Here, we identify Irc5 as a novel interactor of the cohesin complex. Irc5 associates with Scc1 cohesin subunit and contributes to cohesin binding to chromatin. Disruption of IRC5 decreases cohesin levels at centromeres and chromosome arms, causing premature sister chromatid separation. Moreover, reduced cohesin occupancy at the rDNA region in cells lacking IRC5 leads to the loss of rDNA repeats. We also show that the translocase activity of Irc5 is required for its function in cohesion pathway. Finally, we demonstrate that in the absence of Irc5 both the level of chromatin-bound Scc2, a member of cohesin loading complex, and physical interaction between Scc1 and Scc2 are reduced. Our results suggest that Irc5 is an auxiliary factor that is involved in cohesin association with chromatin. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Frequency of HPV in oral cavity squamous cell carcinoma.

PubMed

de Abreu, Priscila Marinho; Có, Anna Clara Gregório; Azevedo, Pedro Leite; do Valle, Isabella Bittencourt; de Oliveira, Karine Gadioli; Gouvea, Sônia Alves; Cordeiro-Silva, Melissa Freitas; Louro, Iúri Drummond; de Podestá, José Roberto Vasconcelos; Lenzi, Jeferson; Sena, Agenor; Mendonça, Elismauro Francisco; von Zeidler, Sandra Lúcia Ventorin

2018-03-27

The prevalence of high-risk human papillomavirus (HPV) DNA in cases of oral cavity squamous cell carcinoma (SCC) varies widely. The aim of this study is to investigate the frequency of high-risk HPV DNA in a large Brazilian cohort of patients with oral cavity SCC. Biopsy and resected frozen and formalin-fixed paraffin-embedded specimens of oral cavity SCC were available from 101 patients who were recruited at two Brazilian centres. Stringent measures with respect to case selection and prevention of sample contamination were adopted to ensure reliability of the data. Nested PCR using MY09/MY11 and GP5 + /GP6 + as well as PGMY09/11 L1 consensus primers were performed to investigate the presence of HPV DNA in the tumours. HPV-positive cases were subjected to direct sequencing. Shapiro-Wilk and Student t test were used to evaluate data normality and to compare the means, respectively. Qualitative variables were analysed by logistic regression. Our results demonstrate that the frequency of high-risk HPV types in oral cavity SCC is very low and is less than 4%. All HPV-positive cases were HPV16. In addition, our results do not show a significant association between the tumour clinical features and the risk factors (tobacco, alcohol and HPV) for oral cavity SCC. In the current study, we observed an overlapping pattern of risk factors that are related to tumour development. This, along with a low frequency of high-risk HPV DNA, supports the findings that HPV is not involved in the genesis of oral cavity SCC in Brazilian population.

Investigating the Prevalence of Human Papilloma Virus in Squamous Cell Carcinoma of the Larynx and Its Correlation with Disease Prognosis.

PubMed

Atighechi, Saeid; Meybodian, Mojtaba; Dadgarnia, Mohammad Hossein; Baradaranfar, Mohammad Hossein; Behniafard, Nasim

2016-05-01

The human papilloma virus (HPV) can play a role in the development of head and neck squamous cell carcinoma (SCC). Our aim was to assess the prevalence of HPV DNA in SCC of the larynx. The impact of HPV infection on patient survival was also evaluated. This case-control study was performed in 44 patients with SCC of the larynx (case group), while the control group comprised samples obtained from cadavers with no previous history of malignancy. A preliminary pathologic evaluation was performed on all samples in the control group (36 samples) to ensure the absence of dysplasia or malignancy. Polymerase chain reaction (PCR) was used to detect HPV DNA. After completing the treatment protocol, patients were followed to assess the impact of HPV infection on overall survival (OS). PCR evaluation in the case group showed that HPV DNA was successfully isolated from 11 (25%) samples, while only two (5.6%) HPV DNA-positive were obtained from cadavers. According to these results, a significant difference was obtained in the prevalence of HPV DNA and laryngeal SCC between cases and controls (P=0.031). No statistically significant difference was observed in the OS of patients with or without HPV infection in the case group (P=0.235). Based on these results, we suggest that the prevalence of HPV infection is higher in laryngeal SCC subjects compared with healthy individuals. Although a longer OS was seen in HPV-positive patients, survival analysis did not show a significant difference in the comparison of HPV-positive and negative findings in SCC patients.

Squamous cell carcinoma of dogs and cats: an ideal test system for human head and neck PDT protocols

NASA Astrophysics Data System (ADS)

Lucroy, Michael D.

2006-02-01

Photodynamic therapy (PDT) is ideally suited for the treatment of head and neck cancer (HNC) in humans. Developing useful PDT protocols for HNC is challenging due to the expense of Phase I and II clinical trials. Moreover, the often-poor predictive value of murine models means that photosensitizers may proceed far into development before problems are noted. Dogs and cats with spontaneous oral squamous cell carcinoma (SCC) share striking similarities with humans affected with oral SCC. These similarities include viral and environmental tobacco smoke as risk factors, location-dependent prognoses, and relative resistance to chemotherapy. The relatively large oral cancers encountered in veterinary patients allow for light and drug dosimetry that are directly applicable to humans. The irregular shape of oral SCC allows a rigorous evaluation of novel photodynamic therapy protocols under field conditions. Because spontaneous tumors in dogs and cats arise in an outbred animal population it is possible to observe an intact host response to PDT. The shorter lifespan of dogs and cats allows rapid accrual of endpoint data. External beam radiation therapy and chemotherapy are commonplace in veterinary medicine, making dogs and cats with spontaneous SCC a useful resource to study the interactions with PDT and other cancer treatment modalities. Our preliminary results demonstrate that PDT is well-tolerated by dogs with oral cancer, and a Phase II clinical trial of zinc-phthalocyanine-based photodynamic therapy is underway in dogs with oral SCC. The usefulness of 5-aminolevulinic acid methyl ester-based PDT is being investigated in cats with oral SCC.

CD117 expression in operable oesophageal squamous cell carcinomas predicts worse clinical outcome

PubMed Central

Fan, Huijie; Yuan, Yuan; Wang, Junsheng; Zhou, Fuyou; Zhang, Mingzhi; Giercksky, Karl-Erik; Nesland, Jahn M; Suo, Zhenhe

2013-01-01

Aims To investigate the aberrant expression of CD117 in oesophageal squamous cell carcinoma (SCC) and its prognostic significance. Methods and results Immunohistochemical staining for CD117 was performed on tissue microarray and routine tissue sections from 157 oesophageal SCC patients and 10 normal oesophageal epithelia adjacent to tumour. The positive rate of CD117 expression was 29.9% in oesophageal SCC tissues, whereas no CD117 expression was detected in the 10 normal oesophageal epithelia. CD117 expression was significantly associated with T stage (P < 0.001), distant metastasis (P = 0.015), lymph node metastasis (P = 0.019), and clinical stage (P = 0.021). Progression-free survival in the patients with CD117-positive tumours was shorter than that in the patients with CD117-negative tumours (P = 0.010). In univariate analyses, CD117 expression was the most significant factor for overall survival of oesophageal SCC patients (P < 0.001), followed by lymph node metastasis (P = 0.001), T stage (P = 0.002), clinical stage (P = 0.006), distant metastasis (P = 0.020), and histological grade (P = 0.027). Multivariate analyses verified that CD117 expression was an independent prognostic marker for oesophageal SCC patients (P = 0.002). In addition, CD117 expression predicted poorer survival in patients without distant metastases. Conclusions CD117 expression in operable oesophageal SCC may be a valuable prognostic marker, and detection of its expression in clinical samples may be useful in defining a subclass of oesophageal SCCs with extremely poor clinical outcome, which may require a specially targeted treatment modality. PMID:23570416

Different patterns of nuclear and mitochondrial penetration by the G3 PAMAM dendrimer and its biotin–pyridoxal bioconjugate BC-PAMAM in normal and cancer cells in vitro

PubMed Central

Uram, Łukasz; Szuster, Magdalena; Filipowicz, Aleksandra; Gargasz, Krzysztof; Wołowiec, Stanisław; Wałajtys-Rode, Elżbieta

2015-01-01

The intracellular localization and colocalization of a fluorescently labeled G3 amine-terminated cationic polyamidoamine (PAMAM) dendrimer and its biotin–pyridoxal (BC-PAMAM) bioconjugate were investigated in a concentration-dependent manner in normal human fibroblast (BJ) and squamous epithelial carcinoma (SCC-15) cell lines. After 24 hours treatment, both cell lines revealed different patterns of intracellular dendrimer accumulation depending on their cytotoxic effects. Cancer cells exhibited much higher (20-fold) tolerance for native PAMAM treatment than fibroblasts, whereas BC-PAMAM was significantly toxic only for fibroblasts at 50 µM concentration. Fibroblasts accumulated the native and bioconjugated dendrimers in a concentration-dependent manner at nontoxic range of concentration, with significantly lower bioconjugate loading. After reaching the cytotoxicity level, fluorescein isothiocyanate-PAMAM accumulation remains at high, comparable level. In cancer cells, native PAMAM loading at higher, but not cytotoxic concentrations, was kept at constant level with a sharp increase at toxic concentration. Mander’s coefficient calculated for fibroblasts and cancer cells confirmed more efficient native PAMAM penetration as compared to BC-PAMAM. Significant differences in nuclear dendrimer penetration were observed for both cell lines. In cancer cells, PAMAM signals amounted to ~25%–35% of the total nuclei area at all investigated concentrations, with lower level (15%–25%) observed for BC-PAMAM. In fibroblasts, the dendrimer nuclear signal amounted to 15% at nontoxic and up to 70% at toxic concentrations, whereas BC-PAMAM remained at a lower concentration-dependent level (0.3%–20%). Mitochondrial localization of PAMAM and BC-PAMAM revealed similar patterns in both cell lines, depending on the extracellular dendrimer concentration, and presented significantly lower signals from BC-PAMAM, which correlated well with the cytotoxicity. PMID:26379435

[Development of cell content and shedding of Prototheca spp. in milk from infected udder quarters of cows].

PubMed

Tenhagen, B A; Hille, A; Schmidt, A; Heuwieser, W

2005-02-01

It was the objective of this study to analyse shedding patterns and somatic cell counts in cows and quarters infected with Prototheca spp. and to evaluate two approaches to identify infected animals by somatic cell count (SCC) or by bacteriological analysis of pooled milk samples. Five lactating dairy cows, chronically infected with Prototheca spp. in at least one quarter were studied over 11 weeks to 13 months. Quarter milk samples and a pooled milk sample from 4 quarters were collected aseptically from all quarters of the cows on a weekly basis. Culture results of quarter milk and pooled samples were compared using cross tabulation. SCC of quarter milk samples and of pooled samples were related to the probability of detection in the infected quarters and cows, respectively. Shedding of Prototheca spp. was continuous in 2 of 8 quarters. In the other quarters negative samples were obtained sporadically or over a longer period (1 quarter). Overall, Prototheca spp. were isolated from 83.6% of quarter milk samples and 77.0% of pooled milk samples of infected quarters and cows. Somatic cell counts were higher in those samples from infected quarters that contained the algae than in negative samples (p < 0.0001). The same applied for composite samples from infected cows. Positive samples had higher SCC than negative samples. However, Prototheca spp. were also isolated from quarter milk and pooled samples with physiological SCC (i.e. < 10(5)/ml). Infected quarters that were dried off did not develop acute mastitis. However, drying off had no effect on the infection, i.e. samples collected at calving or 8 weeks after dry off still contained Prototheca spp. Results indicate that pre-selection of cows to be sampled for Prototheca spp. by SCC and the use of composite samples are probably inadequate in attempts to eradicate the disease. However, due to intermittent shedding of the algae in some cows, single herd sampling using quarter milk samples probably also fails to detect all infected cases. Therefore, continuous monitoring of problem cows with clinical mastitis or increased SCC in herds during eradication programs is recommended.

Efficacy of a high free iodine barrier teat disinfectant for the prevention of naturally occurring new intramammary infections and clinical mastitis in dairy cows.

PubMed

Martins, C M M R; Pinheiro, E S C; Gentilini, M; Benavides, M Lopez; Santos, M V

2017-05-01

Using a natural exposure trial design, the goal of our study was to evaluate the clinical efficacy of an iodine teat disinfectant with barrier properties and a high level of free iodine relative to a conventional iodine teat disinfectant with no barrier properties and low levels of free iodine. During the 18 wk of the trial, quarter milk samples were collected every 2 wk from 385 dairy cows from 2 herds. Cows on both farms were assigned in a balanced way according to milk yield, number of lactation, days in milk, somatic cell count (SCC) and microbiology culture pretrial into one of following groups: nonbarrier post milking teat disinfectant (NBAR; n = 195 cows; 747 quarters) or barrier postmilking teat disinfectant (BAR; n = 190 cows; 728 quarters). Afterward, at each scoring date every 2 wk, milk SCC was quantified in samples from all mammary quarters and microbiologic culture was only performed on milk samples with SCC >200,000 cells/mL for multiparous cows and SCC >100,000 cells/mL for primiparous cows. A new intramammary infection (NIMI) was defined when a quarter had milk SCC <200,000 cells/mL for multiparous cows and <100,000 cells/mL for primiparous without microorganism isolation, and in a subsequent sampling visit had milk SCC >200,000 cells/mL for multiparous cows and >100,000 cells/mL for primiparous cows, and positive microorganism isolation. A quarter could have several NIMI, but only 1 case per specific pathogen was considered. The most frequently isolated microorganism group on both farms was Streptococcus spp. (6.25% of total mammary quarters), followed by coagulase-negative staphylococci (3.6%) and Corynebacterium spp. (1.5%). In the present study, an interaction occurred between treatment and week of trial on the incidence risk of NIMI. Quarters disinfected with BAR had 54 and 37% lower odds of NIMI than quarters disinfected with NBAR at 8 and 16 wk of the trial, respectively; whereas at other weeks of the study both products had similar incidence risks of NIMI. Overall, teats disinfected with BAR had 46% lower odds of acquiring a clinical mastitis than those disinfected with NBAR. We concluded that the postmilking teat disinfectant with barrier properties and higher free iodine content reduced the risk of clinical mastitis, although differences in new infections were detected at only weekly time points. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Enhanced efficacy of AKT and FAK kinase combined inhibition in squamous cell lung carcinomas with stable reduction in PTEN

PubMed Central

Cavazzoni, Andrea; La Monica, Silvia; Alfieri, Roberta; Ravelli, Andrea; Van Der Steen, Nele; Sciarrillo, Rocco; Madeddu, Denise; Lagrasta, Costanza Anna Maria; Quaini, Federico; Bonelli, Mara; Fumarola, Claudia; Cretella, Daniele; Digiacomo, Graziana; Tiseo, Marcello; Peters, Godefridus J.; Ardizzoni, Andrea; Petronini, Pier Giorgio; Giovannetti, Elisa

2017-01-01

Squamous cell lung carcinoma (SCC) accounts for 30% of patients with NSCLC and to date, no molecular targeted agents are approved for this type of tumor. However, recent studies have revealed several oncogenic mutations in SCC patients, including an alteration of the PI3K/AKT pathway, i.e. PI3K point mutations and amplification, AKT mutations and loss or reduced PTEN expression. Prompted by our observation of a correlation between PTEN loss and FAK phosphorylation in a cohort of patients with stage IV SCC, we evaluated the relevance of PTEN loss in cancer progression as well as the efficacy of a new combined treatment with the pan PI3K inhibitor buparlisip and the FAK inhibitor defactinib. An increase in AKT and FAK phosphorylation, associated with increased proliferation and invasiveness, paralleled by the acquisition of mesenchymal markers, and overexpression of the oncomir miR-21 were observed in SKMES-1-derived cell clones with a stable reduction of PTEN. Notably, the combined treatment induced a synergistic inhibition of cell proliferation, and a significant reduction in cell migration and invasion only in cells with reduced PTEN. The molecular mechanisms underlying these findings were unraveled using a specific RTK array that showed a reduction in phosphorylation of key kinases such as JNK, GSK-3 α/β, and AMPK-α2, due to the concomitant decrease in AKT and FAK activation. In conclusion, the combination of buparlisib and defactinib was effective against cells with reduced PTEN and warrants further studies as a novel therapeutic strategy for stage IV SCC patients with loss of PTEN expression. PMID:28881794

Short-term stress enhances cellular immunity and increases early resistance to squamous cell carcinoma.

PubMed

Dhabhar, Firdaus S; Saul, Alison N; Daugherty, Christine; Holmes, Tyson H; Bouley, Donna M; Oberyszyn, Tatiana M

2010-01-01

In contrast to chronic/long-term stress that suppresses/dysregulates immune function, an acute/short-term fight-or-flight stress response experienced during immune activation can enhance innate and adaptive immunity. Moderate ultraviolet-B (UV) exposure provides a non-invasive system for studying the naturalistic emergence, progression and regression of squamous cell carcinoma (SCC). Because SCC is an immunoresponsive cancer, we hypothesized that short-term stress experienced before UV exposure would enhance protective immunity and increase resistance to SCC. Control and short-term stress groups were treated identically except that the short-term stress group was restrained (2.5h) before each of nine UV-exposure sessions (minimum erythemal dose, 3-times/week) during weeks 4-6 of the 10-week UV exposure protocol. Tumors were measured weekly, and tissue collected at weeks 7, 20, and 32. Chemokine and cytokine gene expression was quantified by real-time PCR, and CD4+ and CD8+ T cells by flow cytometry and immunohistochemistry. Compared to controls, the short-term stress group showed greater cutaneous T-cell attracting chemokine (CTACK)/CCL27, RANTES, IL-12, and IFN-gamma gene expression at weeks 7, 20, and 32, higher skin infiltrating T cell numbers (weeks 7 and 20), lower tumor incidence (weeks 11-20) and fewer tumors (weeks 11-26). These results suggest that activation of short-term stress physiology increased chemokine expression and T cell trafficking and/or function during/following UV exposure, and enhanced Type 1 cytokine-driven cell-mediated immunity that is crucial for resistance to SCC. Therefore, the physiological fight-or-flight stress response and its adjuvant-like immuno-enhancing effects, may provide a novel and important mechanism for enhancing immune system mediated tumor-detection/elimination that merits further investigation.

Genetic characterization drives personalized therapy for early-stage non-small-cell lung cancer (NSCLC) patients and survivors with metachronous second primary tumor (MST): A case report.

PubMed

Ding, Xingchen; Wang, Linlin; Liu, Xijun; Sun, Xindong; Yu, Jinming; Meng, Xue

2017-03-01

The pathogenesis and progression of lung cancer is a complicated process in which many genes take part. But molecular gene testing is typically only performed in advanced-stage non-squamous non-small-cell lung cancer (NSCLC). The value of tyrosine kinase inhibitors (TKI) administration is not widely recognized with respect to early-stage NSCLC. Here, we present a case of a man, heavy smoker who initially presented with stage IA lung adenocarcinoma (LADC). Three years after a lung lobectomy, he was diagnosed with advanced lung squamous cell carcinoma (SCC), according to laboratory, imaging, and pathological examinations. The case initially had an early-stage LADC with an L858R epidermal growth factor receptor (EGFR) mutation. A subsequent advanced SCC bearing EGFR L858R/T790M mutations occurred 3 years after surgery. The comprehensive therapy we utilized, including surgical resection for the early-stage lesion and GP chemotherapy and local radiotherapy as the first line therapy along with gefitinib maintenance treatment for the advanced metachronous second primary tumors (MST). The synthetical therapy, have resulted in our patient with remaining alive and progression free for 4.5 years. This case suggests that changes in molecular pathology should be monitored closely throughout cancer progression to guide personalized therapy and improve prognosis. We further review administration of TKI to early-stage NSCLC and to the metachronous second primary tumors (MST) in survivors.

MUC1-Targeted Cancer Cell Photothermal Ablation Using Bioinspired Gold Nanorods.

PubMed

Zelasko-Leon, Daria C; Fuentes, Christina M; Messersmith, Phillip B

2015-01-01

Recent studies have highlighted the overexpression of mucin 1 (MUC1) in various epithelial carcinomas and its role in tumorigenesis. These mucins present a novel targeting opportunity for nanoparticle-mediated photothermal cancer treatments due to their unique antenna-like extracellular extension. In this study, MUC1 antibodies and albumin were immobilized onto the surface of gold nanorods using a "primer" of polydopamine (PD), a molecular mimic of catechol- and amine-rich mussel adhesive proteins. PD forms an adhesive platform for the deposition of albumin and MUC1 antibodies, achieving a surface that is stable, bioinert and biofunctional. Two-photon luminescence confocal and darkfield scattering imaging revealed targeting of MUC1-BSA-PD-NRs to MUC1+ MCF-7 breast cancer and SCC-15 squamous cell carcinoma cells lines. Treated cells were exposed to a laser encompassing the near-infrared AuNR longitudinal surface plasmon and assessed for photothermal ablation. MUC1-BSA-PD-NRs substantially decreased cell viability in photoirradiated MCF-7 cell lines vs. MUC1- MDA-MB-231 breast cancer cells (p < 0.005). Agents exhibited no cytotoxicity in the absence of photothermal treatment. The facile nature of the coating method, combined with targeting and photoablation efficacy, are attractive features of these candidate cancer nanotherapeutics.

Long non-coding RNA CASC15 promotes tongue squamous carcinoma progression through targeting miR-33a-5p.

PubMed

Zuo, Zhibin; Ma, Long; Gong, Zuode; Xue, Lande; Wang, Qibao

2018-05-26

Long non-coding RNAs (lncRNAs) have gained a lot of attention because they participate in several human disorders, including tumors. This study determined the role of LncRNA CASC15 (cancer susceptibility candidate 15) in the development of tongue squamous cell carcinoma (TSCC). Here, we identified that CASC15 expression was upregulated in TSCC samples and cell lines. We showed that overexpression of CASC15 promoted cell proliferation, cycle, and migration in TSCC. In addition, we revealed that miR-33a-5p expression was downregulated in TSCC tissues and cell lines. Moreover, we showed that the expression of CASC15 was negatively related with miR-33a-5p expression in TSCC tissues. Ectopic expression of miR-33a-5p suppressed cell proliferation, cycle, and migration in TSCC. Elevated expression of CASC15 suppressed miR-33a-5p expression and promoted ZEB1 expression in SCC4 cell. Ectopic expression of CASC15 promoted TSCC cell proliferation, cycle, and migration through targeting miR-33a-5p. These results suggested that lncRNA CASC15 and miR-33a-5p might be exploited as new markers of TSCC and were potential treatment targets for TSCC patients.

A Case of Squamous Cell Carcinoma Developing Within a Red-Ink Tattoo.

PubMed

Sherif, Sara; Blakeway, Elizabeth; Fenn, Chris; German, Alyn; Laws, Philip

Cutaneous reactions to tattoos are well reported and include allergic reactions, infections, and foreign body granuloma or may be a presenting sign of sarcoidosis. There have been very few reported cases of squamous cell carcinoma (SCC) arising in tattoo-treated skin. We report a case of SCC arising within a red-ink tattoo and discuss the potential the role of chronic low-grade inflammation in pathogenesis. This should serve to raise awareness of potential tattoo-related serious adverse effects.

Establishment and evaluation of a stable steroidogenic goat Leydig cell line.

PubMed

Zhou, Jinhua; Dai, Rui; Lei, Lanjie; Lin, Pengfei; Lu, Xiaolong; Wang, Xiangguo; Tang, Keqiong; Wang, Aihua; Jin, Yaping

2016-04-01

Leydig cells play a key role in synthesizing androgen and regulating spermatogenesis. The dysfunction of Leydig cells may lead to various male diseases. Although primary Leydig cell cultures have been used, their finite lifespan hinders the assessment of long-term effects. In the present study, primary goat Leydig cells (GLCs) were immortalized via the transfection of a plasmid containing the human telomerase reverse transcriptase (hTERT) gene. The expressions of hTERT and telomerase activity were evaluated in transduced GLCs (hTERT-GLCs). These cells steadily expressed the hTERT gene and exhibited longer telomere lengths at passage 55 that were similar to those of HeLa cells. The hTERT-GLCs at passages 30 and 50 expressed genes that encoded key proteins, enzymes and receptors that are inherent to normal Leydig cells, for example, steroidogenic acute regulatory protein (StAR), cytochrome P450 cholesterol side-chain cleavage enzyme (P450scc), 3β-hydroxysteroid dehydrogenase (3β-HSD) and LH-receptor (LH-R). Additionally, the immortalized goat Leydig cells secreted detectable quantities of testosterone in response to hCG stimulation. Furthermore, this cell line appeared to proliferate more quickly than the control cells, although no neoplastic transformation occurred in vitro. We concluded that the GLCs immortalized with hTERT retained their original characteristics and might provide a useful model for the study of Leydig cell function. © 2015 Japanese Society of Animal Science.

Squamous cell carcinoma in chronic wound: Marjolin ulcer.

PubMed

Cocchetto, Vanessa; Magrin, Paula; de Paula, Roberta Andrade; Aidé, Márcia; Monte Razo, Leonardo; Pantaleão, Luciana

2013-02-15

Cutaneous squamous cell carcinoma (SCC) is a malignant tumor that can occur in normal skin, but commonly evolves from precursor lesions. SCC arising in ulcers is a rare and often aggressive cutaneous malignancy that arises from chronic wounds or old scars and is the most common histological tumor type found in Marjolin ulcer. Most frequently occurs in patients of low socioeconomic status, with limited access to health services, as a result of burns and other neglected injuries. Herein, we report a case of squamous cell carcinoma originating from a longstanding decubitus ulcer in a 56-year-old paraplegic man.

Effect of cell-phone radiofrequency on angiogenesis and cell invasion in human head and neck cancer cells.

PubMed

Alahmad, Yaman M; Aljaber, Mohammed; Saleh, Alaaeldin I; Yalcin, Huseyin C; Aboulkassim, Tahar; Yasmeen, Amber; Batist, Gerald; Moustafa, Ala-Eddin Al

2018-05-13

Today, the cell phone is the most widespread technology globally. However, the outcome of cell-phone radiofrequency on head and neck cancer progression has not yet been explored. The chorioallantoic membrane (CAM) and human head and neck cancer cell lines, FaDu and SCC25, were used to explore the outcome of cell-phone radiofrequency on angiogenesis, cell invasion, and colony formation of head and neck cancer cells, respectively. Western blot analysis was used to investigate the impact of the cell phone on the regulation of E-cadherin and Erk1/Erk2 genes. Our data revealed that cell-phone radiofrequency promotes angiogenesis of the CAM. In addition, the cell phone enhances cell invasion and colony formation of human head and neck cancer cells; this is accompanied by a downregulation of E-cadherin expression. More significantly, we found that the cell phone can activate Erk1/Erk2 in our experimental models. Our investigation reveals that cell-phone radiofrequency could enhance head and neck cancer by stimulating angiogenesis and cell invasion via Erk1/Erk2 activation. © 2018 Wiley Periodicals, Inc.

Case-control study of smoking and non-melanoma skin cancer.

PubMed

Rollison, Dana E; Iannacone, Michelle R; Messina, Jane L; Glass, L Frank; Giuliano, Anna R; Roetzheim, Richard G; Cherpelis, Basil S; Fenske, Neil A; Jonathan, Kristen A; Sondak, Vernon K

2012-02-01

To investigate the association between cigarette smoking and basal and squamous cell carcinomas (BCC and SCC) of the skin, a clinic-based case-control study was conducted in Tampa, FL. Patients with histologically confirmed BCC/SCC were recruited from a university dermatology clinic (n = 215 BCC, 165 SCC). Controls were comprised of individuals with no history of skin cancer who screened negative for skin cancer upon physical examination at the affiliated cancer screening or primary care clinics (n = 315). Information on smoking and other risk factors was obtained from self-administered questionnaires. After adjustment for age, sex, and other skin cancer-risk factors, ever smoking was not associated with BCC (odds ratio (OR) = 1.26, 95% confidence interval (CI) = 0.83-1.92), but was statistically significantly associated with SCC (OR = 1.97, 95% CI = 1.19-3.26), with significant trends observed for SCC associated with increasing cigarettes per day (p = 0.01) and pack-years smoked (p = 0.01). Among men, smoking ≥20 pack-years was associated with non-significant increased risks of BCC (OR = 1.90, 95% CI = 0.88-4.12) and SCC (OR = 1.97, 95% CI = 0.84-4.66), whereas among women, no association was observed with BCC (OR = 0.98, 95% CI = 0.39-2.46) while a statistically significant three-fold risk was observed with SCC (OR = 3.00, 95% CI = 1.02-8.80). Cigarette smoking is more strongly associated with SCC than BCC, particularly among women.

Elevated Squamous Cell Carcinoma Antigen, Cytokeratin 19 Fragment, and Carcinoembryonic Antigen Levels in Diabetic Nephropathy

PubMed Central

Chen, Jianzhong; Zhang, Bin; Chen, Qingguang; Qiu, Yan; Luo, Qian; Gen, Yanna; Meng, Jiali

2017-01-01

Objective We aimed to explore whether squamous cell carcinoma antigen (SCC), cytokeratin 19 fragment (Cyfra21-1), neuron-specific enolase (NSE), and carcinoembryonic antigen (CEA) are elevated in diabetic nephropathy (DN) and the association between urinary albumin-to-creatinine ratio (UACR) and tumor markers in diabetic patients. Methods Nondialysis patients with diabetes (n = 261) and 90 healthy controls were enrolled. DN was defined as an UACR ≥ 30 mg/g in the absence of a urinary tract infection or other renal abnormalities. Results Patients with DN had significantly higher serum SCC, Cyfra21-1, and CEA levels than those with normoalbuminuria and healthy controls. The rates of positive SCC, Cyfra21-1, and CEA significantly increased with increasing urinary albumin excretion (all P for trend < 0.001). In contrast, NSE was not affected by DN. SCC, Cyfra21-1, and CEA were significantly and positively correlated with UACR. In logistic regression, after multivariable adjustment, increased UACR was associated with increased odds ratio of elevated tumor marker levels (all P for trend < 0.05). Conclusions Serum levels of SCC, Cyfra21-1, and CEA are markedly increased with increasing urinary albumin excretion, which affects the specificity for diagnosis for lung cancer. Appropriate interpretation of tumor markers in diabetic patients is mandatory to avoid unnecessary and even hazardous biopsies. PMID:28744310

Short communication: Repeatability of differential goat bulk milk culture and associations with somatic cell count, total bacterial count, and standard plate count.

PubMed

Koop, G; Dik, N; Nielen, M; Lipman, L J A

2010-06-01

The aims of this study were to assess how different bacterial groups in bulk milk are related to bulk milk somatic cell count (SCC), bulk milk total bacterial count (TBC), and bulk milk standard plate count (SPC) and to measure the repeatability of bulk milk culturing. On 53 Dutch dairy goat farms, 3 bulk milk samples were collected at intervals of 2 wk. The samples were cultured for SPC, coliform count, and staphylococcal count and for the presence of Staphylococcus aureus. Furthermore, SCC (Fossomatic 5000, Foss, Hillerød, Denmark) and TBC (BactoScan FC 150, Foss) were measured. Staphylococcal count was correlated to SCC (r=0.40), TBC (r=0.51), and SPC (r=0.53). Coliform count was correlated to TBC (r=0.33), but not to any of the other variables. Staphylococcus aureus did not correlate to SCC. The contribution of the staphylococcal count to the SPC was 31%, whereas the coliform count comprised only 1% of the SPC. The agreement of the repeated measurements was low. This study indicates that staphylococci in goat bulk milk are related to SCC and make a significant contribution to SPC. Because of the high variation in bacterial counts, repeated sampling is necessary to draw valid conclusions from bulk milk culturing. 2010 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Scc2 regulates gene expression by recruiting cohesin to the chromosome as a transcriptional activator during yeast meiosis

PubMed Central

Lin, Weiqiang; Jin, Hui; Liu, Xiuwen; Hampton, Kristin; Yu, Hong-Guo

2011-01-01

To tether sister chromatids, a protein-loading complex, including Scc2, recruits cohesin to the chromosome at discrete loci. Cohesin facilitates the formation of a higher-order chromosome structure that could also influence gene expression. How cohesin directly regulates transcription remains to be further elucidated. We report that in budding yeast Scc2 is required for sister-chromatid cohesion during meiosis for two reasons. First, Scc2 is required for activating the expression of REC8, which encodes a meiosis-specific cohesin subunit; second, Scc2 is necessary for recruiting meiotic cohesin to the chromosome to generate sister-chromatid cohesion. Using a heterologous reporter assay, we have found that Scc2 increases the activity of its target promoters by recruiting cohesin to establish an upstream cohesin-associated region in a position-dependent manner. Rec8-associated meiotic cohesin is required for the full activation of the REC8 promoter, revealing that cohesin has a positive feedback on transcriptional regulation. Finally, we provide evidence that chromosomal binding of cohesin is sufficient for target-gene activation during meiosis. Our data support a noncanonical role for cohesin as a transcriptional activator during cell differentiation. PMID:21508318

Factors influencing variation of bulk milk antibiotic residue occurrence, somatic cell count, and total bacterial count in dairy sheep flocks.

PubMed

Gonzalo, C; Carriedo, J A; García-Jimeno, M C; Pérez-Bilbao, M; de la Fuente, L F

2010-04-01

To study the variations of bulk tank milk variables in dairy ewe flocks and to identify the main target practices and flock groups to improve milk quality and safety, a total of 71,228 records of antibiotic residue (AR) and milk yield and 68,781 records of somatic cell count (SCC) and total bacterial count (TBC) were obtained over 5 yr from the same 209 dairy ewe flocks of the Assaf breed belonging to the Consortium for Ovine Promotion of Castilla-León (Spain). Based on a logistic regression model, year, month, semester, SCC, TBC, dry therapy, and milk yield significantly contributed to AR variation. High SCC was associated with increased AR violations. When antibiotic dry therapy was implemented, AR occurrence was higher than when this practice was not used. A polynomial monthly distribution throughout the year was observed for AR occurrence; the highest values were in autumn, coinciding with low milk yields per flock. Yearly occurrences drastically diminished from 2004 (1.36%) to 2008 (0.30%), probably as a result of effective educational programs. The mixed-model ANOVA of factors influencing variation in SCC and TBC indicated that year, month, AR, dry therapy group, milking type, and year interactions were significant variation factors for SCC and TBC; mathematical model accounted for 74.1 and 35.4% of total variance for each variable, respectively. Differences in management and hygiene practice caused significant SCC and TBC variations among flocks and within flocks throughout the 5-yr study. Over time, continuously dry treated flocks showed lower logSCC (5.80) and logTBC (4.92) than untreated (6.10 and 5.18, respectively) or discontinuously dry treated (6.01 and 5.05, respectively) flocks. Continuously dry treated flocks had lower AR occurrences than did discontinuously dry treated flocks. As a whole, AR occurrence and SCC and TBC bulk tank milk variables can be used for monitoring mammary health and milk hygiene and safety in dairy sheep throughout time. Copyright (c) 2010 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

The Characteristic of S100A7 Induction by the Hippo-YAP Pathway in Cervical and Glossopharyngeal Squamous Cell Carcinoma.

PubMed

Kong, Fei; Li, Yunguang; Hu, Enze; Wang, Rui; Wang, Junhao; Liu, Jin; Zhang, Jinsan; He, Dacheng; Xiao, Xueyuan

2016-01-01

S100A7 is expressed in many squamous cell carcinomas (SCCs). Our previous study revealed that S100A7 was dramatically induced in several SCC cells and activation of the Hippo pathway significantly promoted S100A7 in epidermoid carcinoma cells. However, whether the Hippo pathway regulates S100A7 expression in SCCs remains largely unknown. Here, we uncover that S100A7 induction by the Hippo-YAP pathway displays different characteristic in cervical and glossopharyngeal SCC. In well differentiated HCC94 cervical cells and FaDu pharyngeal cells, S100A7 is easily induced by both suspension and dense culture, which is accompanied by an increase in YAP phosphorylation and a decrease in nuclear YAP. Strikingly, these correlations of S100A7 and YAP reverse after recovery of cell attachment or relief from dense culture. Further examination finds that S100A7 induction is significantly repressed by nuclear YAP, which is validated by activation or inhibition of the Hippo pathway via loss- and/or gain-of- LATS1 and MST1 function. Subsequently, we prove that TEAD1 is required for YAP transcriptional repression of S100A7. However, S100A7 is hardly induced in poorly differentiated SiHa cervical cells and NCI-H226 pulmonary cells even in suspension or activation of the Hippo pathway. More importantly, cervical and lingual SCC tissues array analyses show that S100A7 expression displays the positive correlation with pYAP-S127 and the negative correlation with nuclear YAP in the majority of well differentiated but not in poorly differentiated tissues. Collectively, our findings demonstrate that the different induction of S100A7 toward activation of the Hippo pathway mainly depends on the degree of cell differentiation in cervical and glossopharyngeal SCC.

The relevance of the vitamin D endocrine system (VDES) for tumorigenesis, prevention, and treatment of non-melanoma skin cancer (NMSC)

PubMed Central

Reichrath, Jörg; Reichrath, Sandra

2013-01-01

Solar UV (UV)-B-radiation exerts both beneficial and adverse effects on human health. On the one hand, it is the most important environmental risk factor for the development of non-melanoma skin cancer [NMSC; most importantly basal (BCC) and squamous (SCC) cell carcinomas], that represent the most common malignancies in Caucasian populations. On the other hand, the human body’s requirements of vitamin D are mainly achieved by UV-B-induced cutaneous photosynthesis. This dilemma represents a serious problem in many populations, for an association of vitamin D-deficiency and multiple independent diseases including various types of cancer has been convincingly demonstrated. In line with these findings, epidemiologic and laboratory investigations now indicate that vitamin D and its metabolites have a risk reducing effect for NMSC. Potential mechanisms of action include inhibition of the hedgehog signaling pathway (BCC) and modulation of p53-mediated DNA damage response (SCC). As a consequence of these new findings it can be concluded that UV-B-radiation exerts both beneficial and adverse effects on risk and prognosis of NMSC. It can be assumed that many independent factors, including frequency and dose of UV-B exposure, skin area exposed, and individual factors (such as skin type and genetic determinants of the skin`s vitamin D status and of signaling pathways that are involved in the tumorigenesis of NMSC) determine whether UV-B exposure promotes or inhibits tumorigenesis of NMSC. Moreover, these findings may help to explain many of the differential effects of UV-B radiation on risk of NMSC, including variation in the dose-dependent risk for development of SCC in situ (actinic keratosis, AK), invasive SCC, and BCC. In this review, we analyze the relevance of the vitamin D endocrine system (VDES) for tumorigenesis, prevention, and treatment of NMSC and give an overview of present concepts and future perspectives. PMID:24494041

Zyflamend reduces LTB4 formation and prevents oral carcinogenesis in a 7,12-dimethylbenz[alpha]anthracene (DMBA)-induced hamster cheek pouch model.

PubMed

Yang, Peiying; Sun, Zheng; Chan, Diana; Cartwright, Carrie A; Vijjeswarapu, Mary; Ding, Jibin; Chen, Xiaoxin; Newman, Robert A

2008-11-01

Aberrant arachidonic acid metabolism, especially altered cyclooxygenase and 5-lipoxygenase (LOX) activities, has been associated with chronic inflammation as well as carcinogenesis in human oral cavity tissues. Here, we examined the effect of Zyflamend, a product containing 10 concentrated herbal extracts, on development of 7,12-dimethylbenz[alpha]anthracene (DMBA)-induced inflammation and oral squamous cell carcinoma (SCC). A hamster cheek pouch model was used in which 0.5% DMBA was applied topically onto the left cheek pouch of male Syrian golden hamsters either three times per week for 3 weeks (short term) or 6 weeks (long term). Zyflamend was then applied topically at one of three different doses (25, 50 and 100 microl) onto the left cheek pouch three times for 1 week (short-term study) or chronically for 18 weeks. Zyflamend significantly reduced infiltration of inflammatory cells, incidence of hyperplasia and dysplastic lesions, bromodeoxyuridine-labeling index as well as number of SCC in a concentration-dependent manner. Application of Zyflamend (100 microl) reduced formation of leukotriene B(4) (LTB(4)) by 50% compared with DMBA-treated tissues. The reduction of LTB(4) was concentration dependent. The effect of Zyflamend on inhibition of LTB(4) formation was further confirmed with in vitro cell-based assay. Adding LTB(4) to RBL-1 cells, a rat leukemia cell line expressing high levels of 5-LOX and LTA(4) hydrolase, partially blocked antiproliferative effect of Zyflamend. This study demonstrates that Zyflamend inhibited LTB(4) formation and modulated adverse histopathological changes in the DMBA-induced hamster cheek pouch model. The study suggests that Zyflamend might prevent oral carcinogenesis at the post-initiation stage.

Combination of c-reactive protein and squamous cell carcinoma antigen in predicting postoperative prognosis for patients with squamous cell carcinoma of the esophagus.

PubMed

Feng, Ji-Feng; Chen, Sheng; Yang, Xun

2017-09-08

We initially proposed a useful and novel prognostic model, named CCS [Combination of c-reactive protein (CRP) and squamous cell carcinoma antigen (SCC)], for predicting the postoperative survival in patients with esophageal squamous cell carcinoma (ESCC). Two hundred and fifty-two patients with resectable ESCC were included in this retrospective study. A logistic regression was performed and yielded a logistic equation. The CCS was calculated by the combined CRP and SCC. The optimal cut-off value for CCS was evaluated by X-tile program. Univariate and multivariate analyses were used to evaluate the predictive factors. In addition, a novel nomogram model was also performed to predict the prognosis for patients with ESCC. In the current study, CCS was calculated as CRP+6.33 SCC according to the logistic equation. The optimal cut-off value was 15.8 for CCS according to the X-tile program. Kaplan-Meier analyses demonstrated that high CCS group had a significantly poor 5-year cancer-specific survival (CSS) than low CCS group (10.3% vs. 47.3%, P <0.001). According to multivariate analyses, CCS ( P =0.004), but not CRP ( P =0.466) or SCC ( P =0.926), was an independent prognostic factor. A nomogram could be more accuracy for CSS (Harrell's c-index: 0.70). The CCS is a usefull and independent predictive factor in patients with ESCC.

Non-melanoma skin cancer: United Kingdom National Multidisciplinary Guidelines.

PubMed

Newlands, C; Currie, R; Memon, A; Whitaker, S; Woolford, T

2016-05-01

This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer patients in the UK. This paper provides consensus recommendations on the management of cutaneous basal cell carcinoma and squamous cell carcinoma in the head and neck region on the basis of current evidence. Recommendations • Royal College of Pathologists minimum datasets for NMSC should be adhered to in order to improve patient care and help work-force planning in pathology departments. (G) • Tumour depth is of critical importance in identifying high-risk cutaneous squamous cell carcinoma (cSCC), and should be reported in all cases. (R) • Appropriate imaging to determine the extent of primary NMSC is indicated when peri-neural involvement or bony invasion is suspected. (R) • In the clinically N0 neck, radiological imaging is not beneficial, and a policy of watchful waiting and patient education can be adopted. (R) • Patients with high-risk NMSC should be treated by members of a skin cancer multidisciplinary team (MDT) in secondary care. (G) • Non-infiltrative basal cell carcinoma (BCC) <2 cm in size should be excised with a margin of 4-5 mm. Smaller margins (2-3 mm) may be taken in sites where reconstructive options are limited, when reconstruction should be delayed. (R) • Where there is a high risk of recurrence, delayed reconstruction or Mohs micrographic surgery should be used. (R) • Surgical excision of low-risk cSCC with a margin of 4 mm or greater is the treatment of choice. (R) • High-risk cSCC should be excised with a margin of 6 mm or greater. (R). • Mohs micrographic surgery has a role in some high-risk cSCC cases following MDT discussion. (R) • Delayed reconstruction should be used in high-risk cSCC. (G) • Intra-operative conventional frozen section in cSCC is not recommended. (G) • Radiotherapy (RT) is an effective therapy for primary BCC and cSCC. (R) • Re-excision should be carried out for incompletely excised high-risk BCC or where there is deep margin involvement. (R) • Incompletely excised high-risk cSCC should be re-excised. (R) • Further surgery should involve confirmed marginal clearance before reconstruction. (R) • P+ N0 disease: Resection should include involved parotid tissue, combined with levels I-III neck dissection, to include the external jugular node. (R) • P+ N+ disease: Resection should include level V if that level is clinically or radiologically involved. (R) • Adjuvant RT should include level V if not dissected. (R) • P0 N+ disease: Anterior neck disease should be managed with levels I-IV neck dissection to include the external jugular node. (R) • P0 N+ posterior echelon nodal disease (i.e. occipital or post-auricular) should undergo dissection of levels II-V, with sparing of level I. (R) • Consider treatment of the ipsilateral parotid if the primary site is the anterior scalp, temple or forehead. (R) • All patients should receive education in self-examination and skin cancer prevention measures. (G) • Patients who have had a single completely excised BCC or low-risk cSCC can be discharged after a single post-operative visit. (G) • Patients with an excised high-risk cSCC should be reviewed three to six monthly for two years, with further annual review depending upon clinical risk. (G) • Those with recurrent or multiple BCCs should be offered annual review. (G).

The analysis of milk components and pathogenic bacteria isolated from bovine raw milk in Korea.

PubMed

Park, Y K; Koo, H C; Kim, S H; Hwang, S Y; Jung, W K; Kim, J M; Shin, S; Kim, R T; Park, Y H

2007-12-01

Bovine mastitis can be diagnosed by abnormalities in milk components and somatic cell count (SCC), as well as by clinical signs. We examined raw milk in Korea by analyzing SCC, milk urea nitrogen (MUN), and the percentages of milk components (milk fat, protein, and lactose). The associations between SCC or MUN and other milk components were investigated, as well as the relationships between the bacterial species isolated from milk. Somatic cell counts, MUN, and the percentages of milk fat, protein, and lactose were analyzed in 30,019 raw milk samples collected from 2003 to 2006. The regression coefficients of natural logarithmic-transformed SCC (SCCt) on milk fat (-0.0149), lactose (-0.8910), and MUN (-0.0096), and those of MUN on milk fat (-0.3125), protein (-0.8012), and SCCt (-0.0671) were negative, whereas the regression coefficient of SCCt on protein was positive (0.3023). When the data were categorized by the presence or absence of bacterial infection in raw milk, SCCt was negatively associated with milk fat (-0.0172), protein (-0.2693), and lactose (-0.4108). The SCCt values were significantly affected by bacterial species. In particular, 104 milk samples infected with Staphylococcus aureus had the highest SCCt (1.67) compared with milk containing other mastitis-causing bacteria: coagulase-negative staphylococci (n = 755, 1.50), coagulase-positive staphylococci (except Staphylococcus aureus; n = 77, 1.59), Streptococcus spp. (Streptococcus dysgalactiae, n = 37; Streptococcus uberis, n = 12, 0.83), Enterococcus spp. (n = 46, 1.04), Escherichia coli (n = 705, 1.56), Pseudomonas spp. (n = 456, 1.59), and yeast (n = 189, 1.52). These results show that high SCC and MUN negatively affect milk components and that a statistical approach associating SCC, MUN, and milk components by bacterial infection can explain the patterns among them. Bacterial species present in raw milk are an important influence on SCC in Korea.

Chemoradiotherapy, with adjuvant surgery for local control, confers a durable survival advantage in adenocarcinoma and squamous cell carcinoma of the oesophagus.

PubMed

Bass, G A; Furlong, H; O'Sullivan, K E; Hennessy, T P J; Walsh, T N

2014-04-01

Oesophageal cancer usually presents with systemic disease, necessitating systemic therapy. Neo-adjuvant chemoradiotherapy improves short-term survival, but its long-term impact is disputed because of limited accrual, treatment-protocol heterogeneity and a short follow-up of randomised trials. Long-term results of two simultaneous randomised controlled trials (RCTs) comparing neo-adjuvant chemo-radiotherapy and surgery (MMT) with surgical monotherapy were examined, and the response of adenocarcinoma (AC) and squamous cell carcinoma (SCC) to identical regimens compared. Between 1990 and 1997, two RCTs were undertaken on 211 patients. Patients with AC (n=113) or SCC (n=98) were separately-randomised to identical protocols of MMT or surgical monotherapy. 211 patients were followed to 206 months; 104 patients were randomised to MMT (58 AC and 46 SCC, respectively) and 107 to surgery. MMT provided a significant survival-advantage over surgical monotherapy for AC (P=0.004), SCC (P=0.01). There was a 54% relative risk-reduction in lymph-node metastasis following MMT, compared with surgery (64% versus 29%, P<0.001). MMT produced a pathologic complete response (pCR) in 25% and 31% of AC and SCC, respectively. Survival advantage accrued to MMT, pCR and node-negative patients: AC pCR versus surgical monotherapy (P=0.001); residual disease following MMT versus surgical monotherapy (P=0.008); SCC pCR versus surgical monotherapy (P=0.033). A survival advantage for MMT persisted long-term in AC and was replicated in SCC. MMT produced loco-regional tumour down-staging to extinction in 25-31% of patients, potentially permitting personalised treatment in this cohort that avoids the morbidity and mortality associated with resection. Node-negative patients with residual localised disease following MMT had a survival advantage over node-negative patients following surgery alone, supporting a systemic effect on micro-metastatic disease. Copyright © 2014 Elsevier Ltd. All rights reserved.

The mannose 6-phosphate-binding sites of M6P/IGF2R determine its capacity to suppress matrix invasion by squamous cell carcinoma cells

PubMed Central

Probst, Olivia C.; Karayel, Evren; Schida, Nicole; Nimmerfall, Elisabeth; Hehenberger, Elisabeth; Puxbaum, Verena; Mach, Lukas

2013-01-01

The M6P (mannose 6-phosphate)/IGF2R (insulin-like growth factor II receptor) interacts with a variety of factors that impinge on tumour invasion and metastasis. It has been shown that expression of wild-type M6P/IGF2R reduces the tumorigenic and invasive properties of receptor-deficient SCC-VII squamous cell carcinoma cells. We have now used mutant forms of M6P/IGF2R to assess the relevance of the different ligand-binding sites of the receptor for its biological activities in this cellular system. The results of the present study demonstrate that M6P/IGF2R does not require a functional binding site for insulin-like growth factor II for inhibition of anchorage-independent growth and matrix invasion by SCC-VII cells. In contrast, the simultaneous mutation of both M6P-binding sites is sufficient to impair all cellular functions of the receptor tested. These findings highlight that the interaction between M6P/IGF2R and M6P-modified ligands is not only important for intracellular accumulation of lysosomal enzymes and formation of dense lysosomes, but is also crucial for the ability of the receptor to suppress SCC-VII growth and invasion. The present study also shows that some of the biological activities of M6P/IGF2R in SCC-VII cells strongly depend on a functional M6P-binding site within domain 3, thus providing further evidence for the non-redundant cellular functions of the individual carbohydrate-binding domains of the receptor. PMID:23347038

Milk losses associated with somatic cell counts by parity and stage of lactation.

PubMed

Gonçalves, Juliano L; Cue, Roger I; Botaro, Bruno G; Horst, José A; Valloto, Altair A; Santos, Marcos V

2018-05-01

The reduction of milk production caused by subclinical mastitis in dairy cows was evaluated through the regression of test-day milk yield on log-transformed somatic cell counts (LnSCC). Official test-day records (n = 1,688,054) of Holstein cows (n = 87,695) were obtained from 719 herds from January 2010 to December 2015. Editing was performed to ensure both reliability and consistency for the statistical analysis, and the final data set comprised 232,937 test-day records from 31,692 Holstein cows in 243 herds. A segmented regression was fitted to estimate the cutoff point in the LnSCC scale where milk yield started to be affected by mastitis. The statistical model used to explain daily milk yield included the effect of herd as a random effect and days in milk and LnSCC as fixed effects regressions, and analyses were performed by parity and stage of lactation. The cutoff point where milk yield starts to be affected by changes in LnSCC was estimated to be around 2.52 (the average of all estimates of approximately 12,400 cells/mL) for Holsteins cows from Brazilian herds. For first-lactation cows, milk losses per unit increase of LnSCC had estimates around 0.68 kg/d in the beginning of the lactation [5 to 19 d in milk (DIM)], 0.55 kg/d in mid-lactation (110 to 124 DIM), and 0.97 kg/d at the end of the lactation (289 to 304 DIM). For second-lactation cows, milk losses per unit increase of LnSCC had estimates around 1.47 kg/d in the beginning of the lactation (5 to 19 DIM), 1.09 kg/d in mid-lactation (110 to 124 DIM), and 2.45 kg/d at the end of the lactation (289 to 304 DIM). For third-lactation cows, milk losses per unit increase of LnSCC had estimates around 2.22 kg/d in the beginning of the lactation (5 to 19 DIM), 1.13 kg/d in mid-lactation (140 to 154 DIM), and 2.65 kg/d at the end of the lactation (289 to 304 DIM). Daily milk losses caused by increased LnSCC were dependent on parity and stage of lactation, and these factors should be considered when estimating losses associated with subclinical mastitis. Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

The ultrastructural surface morphology of oral cancer cells and keratinocytes after exposure to chitosan

NASA Astrophysics Data System (ADS)

Fatimah; Sarsito, A. S.; Wimardhani, Y. S.

2017-08-01

Low-molecular-weight chitosan (LMWC) has the same selective cytotoxic effects on oral cancer cells as cisplatin. The cell deaths caused by the anticancer characteristics of chitosan show that apoptosis is not the death pathway of the primary cells involved. The interactions between LMWC and the cells need to be explored. The objective of this study was to compare the ultrastructural morphology of oral Squamous Cell Carcinoma (SCC Ca)-922 and noncancer keratinocyte HaCaT cell lines after exposure to LMWC and cisplatin. The cells were treated with LMWC and cisplatin, and their ultrastructural morphology was analyzed using scanning electron micrographs. Features of early apoptosis, seen as the loss of microvilli, were detected in the LMWC-exposed Ca9-22 cells, and there was a material surrounding the cells. In contrast, the LMWC-exposed HaCaT cells showed no changes related to apoptosis. The results were the opposite when cisplatin was used. This study confirms that there are differences in the ultrastructural surface morphology of LMWC-exposed and cisplatin-exposed oral cancer cells and keratinocytes that could be correlated with their biological activity.

The economic burden of occupational non-melanoma skin cancer due to solar radiation.

PubMed

Mofidi, Amirabbas; Tompa, Emile; Spencer, James; Kalcevich, Christina; Peters, Cheryl E; Kim, Joanne; Song, Chaojie; Mortazavi, Seyed Bagher; Demers, Paul A

2018-06-01

Solar ultraviolet (UV) radiation is the second most prevalent carcinogenic exposure in Canada and is similarly important in other countries with large Caucasian populations. The objective of this article was to estimate the economic burden associated with newly diagnosed non-melanoma skin cancers (NMSCs) attributable to occupational solar radiation exposure. Key cost categories considered were direct costs (healthcare costs, out-of-pocket costs (OOPCs), and informal caregiver costs); indirect costs (productivity/output costs and home production costs); and intangible costs (monetary value of the loss of health-related quality of life (HRQoL)). To generate the burden estimates, we used secondary data from multiple sources applied to computational methods developed from an extensive review of the literature. An estimated 2,846 (5.3%) of the 53,696 newly diagnosed cases of basal cell carcinoma (BCC) and 1,710 (9.2%) of the 18,549 newly diagnosed cases of squamous cell carcinoma (SCC) in 2011 in Canada were attributable to occupational solar radiation exposure. The combined total for direct and indirect costs of occupational NMSC cases is $28.9 million ($15.9 million for BCC and $13.0 million for SCC), and for intangible costs is $5.7 million ($0.6 million for BCC and $5.1 million for SCC). On a per-case basis, the total costs are $5,670 for BCC and $10,555 for SCC. The higher per-case cost for SCC is largely a result of a lower survival rate, and hence higher indirect and intangible costs. Our estimates can be used to raise awareness of occupational solar UV exposure as an important causal factor in NMSCs and can highlight the importance of occupational BCC and SCC among other occupational cancers.

Phosphorylated Epidermal Growth Factor Receptor Expression Is Associated With Clinicopathologic Parameters and Patient Survival in Mobile Tongue Squamous Cell Carcinoma.

PubMed

Theocharis, Stamatios; Giaginis, Constantinos; Dana, Eugene; Thymara, Irene; Rodriguez, Jose; Patsouris, Efstratios; Klijanienko, Jerzy

2017-03-01

Phosphorylated epidermal growth factor receptor (pEGFR) activates several signaling pathways, resulting in tumor-promoting cellular activities, and has been implicated in malignant transformation and disease progression. The present study evaluated the clinical significance of pEGFR protein expression in mobile tongue squamous cell carcinoma (SCC). The present cohort study included 48 patients with mobile tongue SCC. We evaluated whether pEGFR immunohistochemical protein expression is associated with clinical variables and patient outcome. Of the 48 patients included in the present cohort study, 25 were men and 23 were women. The median patient age was 60 years (interquartile range 53 to 72). pEGFR protein expression was significantly increased in well-differentiated tumors compared with poorly differentiated tumors (P = .001). Elevated pEGFR protein expression was significantly more frequently observed in mobile tongue SCC cases with a well-defined tumor shape and an earlier disease stage (P = .010 and P = .019, respectively). Patients with mobile tongue SCC presenting with elevated pEGFR expression had longer overall and disease-free survival times compared with those with low pEGFR expression (P = .015 and P = .006, respectively; log-rank test). On multivariate analysis, pEGFR expression proved to be an independent prognostic factor of both overall and disease-free survival (P = .008 and P = .044, respectively; Cox regression analysis). The results of the present study support evidence that the pEGFR signaling pathway might be implicated in the malignant transformation of mobile tongue SCC. Additional studies are recommended to validate whether pEGFR could be used as a potential biomarker and therapeutic target in mobile tongue SCC. Copyright © 2016 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Squamous Cell Carcinoma: Clinical and Pathological Features and Associated Risk Factors in an Observational Study of 118 Patients.

PubMed

Díaz-Corpas, T; Morales-Suárez-Varela, M; Rausell Fontestad, N; Fuertes Prósper, A; Marquina-Vila, A; Jordá-Cuevas, E

2015-12-01

In the latest edition of its cancer staging manual, the American Joint Committee on Cancer (AJCC) revised the criteria for staging squamous cell carcinoma (SCC) by introducing high-risk tumor features to define tumor stage (T) and help to identify tumors with a higher risk of metastasis. The aim of this study was to investigate the characteristics associated with SCC meeting the high-risk criteria defined by the AJCC for T2 lesions. We performed a case-case observational study in which patients with SCC were included over a period of 18 months. We collected clinical, anthropometric, and tumor data, and analyzed these using PASW Statistics (SPSS) version 18. One-hundred eighteen patients, the majority of whom were men, were included. Mean age was 77 years. Over 70% of the tumors were located in the head region and a majority of tumors measured 2 cm or less. The prevalence of SCC T2 was 61.9%. The risk factors significantly associated with SCC T2 were an age of over 85 years (odds ratio [OR], 4.48), location in the head and neck region (OR, 3.38), presence of solar elastosis in the peritumoral tissue (OR, 2.08), a higher tumor growth rate (>1.5 mm·wk(-1); OR, 5.73), and higher cumulative exposure to smoking (>20 pack-years, OR, 3.63). Advanced age, location in the head and neck region, presence of solar elastosis, high tumor growth rate, and high cumulative smoking exposure were all significantly associated with the presence of SCC T2. Copyright © 2015 Elsevier España, S.L.U. and AEDV. All rights reserved.

Treatment outcomes of patients with primary squamous cell carcinoma of the retromolar trigone.

PubMed

Rizvi, Zain H; Alonso, Jose E; Kuan, Edward C; St John, Maie A

2018-05-14

Squamous cell carcinoma of the retromolar trigone (RMT SCC) is a relatively uncommon primary site for oral cavity malignancy. However, given its proximity to the mandible and buccal mucosa, RMT SCC typically exhibits early invasion and generally presents at an advanced stage. Large-sample studies are needed to assess the epidemiology and clinical outcomes of this tumor. Our aim was to describe the determinants of survival in patients with RMT SCC. Retrospective cohort study. Retrospective, population-based cohort study of patients in the Surveillance, Epidemiology, and End Results tumor registry who were diagnosed with RMT SCC from 1973 to 2012. Primary endpoints were overall survival (OS) and disease-specific survival (DSS). A total of 4,022 cases of RMT SCC were identified. The mean age at diagnosis was 65 years. Thirty-nine percent of cases presented with stage IV disease. The median OS by stages I to IV were 73.7, 52.4, 27.5, and 23.4 months, respectively (P < .05). Overall, 34.3% of patients underwent surgery, 23.5% received radiation therapy, and 34.1% had both surgical and radiation therapy. On multivariate analysis, advanced age, greater tumor size, and advanced stage were associated with worse OS and DSS (P < .05), surgery predicted improved OS and DSS (P < .05), and radiation therapy predicted improved OS only (P < .05). RMT SCC is an aggressive malignancy that portends a poor prognosis, though early-stage tumors (stages I and II) have significantly improved survival. Any surgical intervention independently predicted higher survival outcomes. There may be a role of dual modality approaches, particularly for larger tumors. 4. Laryngoscope, 2018. © 2018 The American Laryngological, Rhinological and Otological Society, Inc.

Investigating the Prevalence of Human Papilloma Virus in Squamous Cell Carcinoma of the Larynx and Its Correlation with Disease Prognosis

PubMed Central

Atighechi, Saeid; Meybodian, Mojtaba; Dadgarnia, Mohammad Hossein; Baradaranfar, Mohammad Hossein; Behniafard, Nasim

2016-01-01

Introduction: The human papilloma virus (HPV) can play a role in the development of head and neck squamous cell carcinoma (SCC). Our aim was to assess the prevalence of HPV DNA in SCC of the larynx. The impact of HPV infection on patient survival was also evaluated. Materials and Methods: This case-control study was performed in 44 patients with SCC of the larynx (case group), while the control group comprised samples obtained from cadavers with no previous history of malignancy. A preliminary pathologic evaluation was performed on all samples in the control group (36 samples) to ensure the absence of dysplasia or malignancy. Polymerase chain reaction (PCR) was used to detect HPV DNA. After completing the treatment protocol, patients were followed to assess the impact of HPV infection on overall survival (OS). Results: PCR evaluation in the case group showed that HPV DNA was successfully isolated from 11 (25%) samples, while only two (5.6%) HPV DNA-positive were obtained from cadavers. According to these results, a significant difference was obtained in the prevalence of HPV DNA and laryngeal SCC between cases and controls (P=0.031). No statistically significant difference was observed in the OS of patients with or without HPV infection in the case group (P=0.235). Conclusion: Based on these results, we suggest that the prevalence of HPV infection is higher in laryngeal SCC subjects compared with healthy individuals. Although a longer OS was seen in HPV-positive patients, survival analysis did not show a significant difference in the comparison of HPV-positive and negative findings in SCC patients. PMID:27429948

Lack of Correlation between Aberrant p16, RAR-β2, TIMP3, ERCC1, and BRCA1 Protein Expression and Promoter Methylation in Squamous Cell Carcinoma Accompanying Candida albicans-Induced Inflammation

PubMed Central

Terayama, Yui; Matsuura, Tetsuro; Ozaki, Kiyokazu

2016-01-01

Hyperplastic candidiasis is characterized by thickening of the mucosal epithelia with Candida albicans infection with occasional progression to squamous cell carcinoma (SCC). C. albicans is a critical factor in tumor development; however, the oncogenic mechanism is unclear. We have previously produced an animal model for hyperplastic candidiasis in the rat forestomach. In the present study, we investigate whether impaired DNA methylation and associated protein expression of tumor suppressor and DNA repair genes are involved in the SCC carcinogenesis process using this hyperplastic candidiasis model. Promoter methylation and protein expression were analyzed by methylation specific PCR and immunohistochemical staining, respectively, of 5 areas in the forestomachs of alloxan-induced diabetic rats with hyperplastic candidiasis: normal squamous epithelia, squamous hyperplasia, squamous hyperplasia adjacent to SCC, squamous hyperplasia transitioning to SCC, and SCC. We observed nuclear p16 overexpression despite increases in p16 gene promoter methylation during the carcinogenic process. TIMP3 and RAR-β2 promoter methylation progressed until the precancerous stage but disappeared upon malignant transformation. In comparison, TIMP3 protein expression was suppressed during carcinogenesis and RAR-β2 expression was attenuated in the cytoplasm but enhanced in nuclei. ERCC1 and BRCA1 promoters were not methylated at any stage; however, their protein expression disappeared beginning at hyperplasia and nuclear protein re-expression in SCC was observed only for ERCC1. These results suggest that aberrant p16, RAR-β2, TIMP3, ERCC1, and BRCA1 expression might occur that is inconsistent with the respective gene promoter methylation status, and that this overexpression might serve to promote the inflammatory carcinogenesis caused by C. albicans infection. PMID:27410681

Anal Cancer Incidence in the United States, 1977–2011: Distinct Patterns by Histology and Behavior

PubMed Central

Shiels, Meredith S.; Kreimer, Aimée R.; Coghill, Anna E.; Darragh, Teresa M.; Devesa, Susan S.

2015-01-01

Background Although anal squamous cell carcinoma (SCC) and adenocarcinoma (ADC) are generally combined in cancer surveillance, their etiologies likely differ. Here, we describe demographic characteristics and trends in incidence rates (IRs) of anal cancer by histology (SCC, ADC) and behavior (invasive, in situ) in the United States. Methods With data from the Surveillance, Epidemiology and End Results (SEER) Program, we estimated age-adjusted anal cancer IRs across behavior/histology by demographic and tumor characteristics for 2000–2011. Trends in IRs and annual percent changes during 1977–2011 were also estimated and compared to rectal cancer. Results Women had higher rates of SCC (rate ratio [RR]=1.45; 95%CI 1.40–1.50) and lower rates of ADC (RR=0.68; 95%CI 0.62–0.74) and squamous carcinoma in situ (CIS) (RR=0.36; 95%CI 0.34–0.38) than men. Blacks had lower rates of SCC (RR=0.82; 95%CI 0.77–0.87) and CIS (RR=0.90; 95%CI 0.83–0.98) than non-Hispanic whites, but higher rates of ADC (RR=1.48; 95%CI 1.29–1.70). Anal cancer IRs were higher in men and blacks aged <40 years. During 1992–2011, SCC IRs increased 2.9%/year, ADC IRs declined non-significantly, and CIS IRs rose 14.2%/year. SCC and ADC IR patterns and trends were similar across anal and rectal cancers. Conclusions Rates of anal SCC and CIS have increased strongly over time, in contrast to rates of anal ADC, similar to trends observed for rectal SCC and ADC. Impact Anal SCC and ADC likely have different etiologies, but may have similar etiologies to rectal SCC and ADC, respectively. Strong increases in CIS IRs over time may reflect anal cancer screening patterns. PMID:26224796

[Sickle-cell crisis in the child and teenager in Brazzaville, Congo. A retrospective study of 587 cases].

PubMed

Babela, J R Mabiala; Nzingoula, S; Senga, P

2005-12-01

Using files related to children admitted at the Brazzaville teaching hospital (Congo) between May 1995 and May 2002, the authors have studied the part of sickle cell crisis (SCC) in the sickle cell disease, have assessed the epidemiological particularities, the relation between some clinical, biological factors as well as the severity of the disease. On the whole, 587 SCC have been observed in homozygous SS children aged 6 to 17. The distribution was as follows: painful osteo-articular crisis (58.6%), abdominal crisis (23.5%), acute chest syndrome (14%), neurological strokes (3.2%) and priapism (0.7%). The neurological strokes (75%) and the hand-foot syndrome (77.8%) were predominant in male. As regards the interaction age-localization of the crisis, the hand-foot syndrome mainly concerned children under five, long bones and rachis impairment those aged 11 to 15; abdominal and neurological crisis were observed especially before the age of 10, the acute chest syndrome after 10 (68.3%). Malaria (48.9%) and bacterial or viral infections (24.5%) proved to be the triggering factors when these are identified (188 cases). SCC occurred in 67.5% of the cases during the hot and rainy seasons. Moreover the haemoglobin F rate above 10% was correlated with a low prevalence of SCC, in particular the potentially severe crisis, revealing at the same time its protective value. These results show that SCC, by their frequency and/or their severity constitute a major handicap when the vital prognosis is not involved. Rigorous health habits, appropriate vaccination programme, adequate malarial prophylaxis, optimal transfusional strategy and especially the use of hydroxyurea, prove to be urgent preventive measures to put into practice. Their efficient implementation will provide a better quality of life to the sickle cell patient and will decrease the risks of severe crisis.

Investigation of relationship between precursor of miRNA-944 and its mature form in lung squamous-cell carcinoma - the diagnostic value.

PubMed

Powrózek, Tomasz; Mlak, Radosław; Dziedzic, Marcin; Małecka-Massalska, Teresa; Sagan, Dariusz

2018-03-01

MicroRNA (miRNA) are attractive markers of lung cancer, due to their regulatory role in cell cycle. However, we know more about function of miRNA in cancer development, there is still little known about role of their precursors (primary miRNA; pri-miRNA) in tumorgenesis. In present study we investigated potential role of miRNA-944 and its precursor pri-miRNA-944 in development of squamous-cell lung cancer (SCC) and explored interdependence between miRNA precursor and its mature form. This is a first available literature report analyzing pri-miRNA as a cancer diagnostic marker. Expression of miRNA-944 and its precursor was analyzed in 58 fresh-frozen tissues of non-small cell lung cancer and corresponding adjacent non-cancerous tissues using qRT-PCR. Expression of pri-miRNA-944 was correlated with TP63 and miRNA-944. Using ROC analysis diagnostic accuracy of studied markers was evaluated. miRNA-944 and its precursor were significantly overexspressed in SCC compared to adenocarcinoma (AC) and non-cancerous tissue. pri-miRNA-944 strongly and positively correlated with TP63 (r = 0.739, p < 0.001) and with mature miRNA-944 expression (r = 0.691, p < 0.001). Also, TP63 expression significantly correlated with mature miRNA (r = 0.785, p < 0.001). Combined analysis of pri-miRNA-944 and mature miRNA-944 allowed to distinguish SCC tissue form AC with sensitivity of 93.3% and specificity of 100% (AUC = 0.978), and SCC from non-cancerous tissue with 92.9% sensitivity and 100% specificity (AUC = 0.992). We assumed that pri-miRNA-944 and miRNA-944 may be involved in early squamous-type differentiation of lung tumors. Moreover, analysis of both markers provided high diagnostic accuracy for SCC detection. Copyright © 2018 Elsevier GmbH. All rights reserved.

Short communication: role of Mycoplasma arginini in mastitis caused by Streptococcus dysgalactiae.

PubMed

Stipkovits, Laszlo; Somogyi, Maria; Asvanyi, Balazs; Toth, Agnes; Szathmary, Susan

2013-03-01

We performed a comparative study on the development of mastitis induced by Mycoplasma arginini or Streptococcus dysgalactiae after challenging the cows. Mycoplasma arginini did not cause any clinical symptoms on its own, resulting in only a transient increase of somatic cell count (SCC; increase ranging from 0.5 × 10(6) to 0.8 × 10(6) cells/mL) and a slight decrease of milk production (10%) for 5 d. In contrast, Strep. dysgalactiae induced more severe clinical signs in animals and SCC increased to 1.60 × 10(6) to 2.11 × 10(6) cells/mL for 10 d. In addition, milk production decreased (22.9 to 27.0%) for 10 d. After 3 mo (2 mo after the first challenge), animals that were challenged previously with M. arginini were rechallenged with Strep. dysgalactiae. Severe clinical mastitis developed, with very high SCC (5.00 × 10(6) to 21.5 × 10(6) cells/mL), and a very significant reduction of milk production (28.6 to 68.7%), which lasted more than 4 wk, was observed. The severe clinical mastitis developed not only in cows inoculated with Strep. dysgalactiae andM. arginini in the same udder quarter but also in cows infected in the quarter previously not challenged with mycoplasma. Cows challenged first with Strep. dysgalactiae and rechallenged with M. arginini 2 mo later developed only slight changes in both SCC and milk production, similar to those when the cows were challenged with M. arginini alone. We conclude that M. arginini infection does not cause remarkable mastitis (characterized by decrease in milk production and increase of SCC) but it significantly predisposes animals to infection with Strep. dysgalactiae, leading to severe clinical mastitis. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Tretinoin and the prevention of keratinocyte carcinoma (Basal and squamous cell carcinoma of the skin): a veterans affairs randomized chemoprevention trial.

PubMed

Weinstock, Martin A; Bingham, Stephen F; Digiovanna, John J; Rizzo, Amilcar E; Marcolivio, Kim; Hall, Russell; Eilers, David; Naylor, Mark; Kirsner, Robert; Kalivas, James; Cole, Gary; Vertrees, Julia E

2012-06-01

Keratinocyte carcinoma (KC) is the most common cancer in the United States, with no proven means for prevention other than systemic retinoids, which have significant toxicity, and sunscreen. Topical tretinoin has been used for KC chemoprevention, although this use is unproven. Hence, we conducted the randomized Veterans Affairs Topical Tretinoin Chemoprevention Trial of high-dose topical tretinoin for KC prevention. We randomized 1,131 patients to topical 0.1% tretinoin or a matching vehicle control for 1.5-5.5 years. The primary outcomes were time to development of new basal cell carcinoma (BCC) and new invasive squamous cell carcinoma (SCC) on the face or ears. The effects were not significant (P=0.3 for BCC and P=0.4 for SCC). The proportions of the tretinoin and control groups who developed a BCC at 5 years were 53 and 54% and an invasive SCC at 5 years were 28 and 31%. These differences (95% confidence intervals) were: for BCC, 1.0% (-6.5, 8.6%); for SCC, 3.6% (-3.1, 10.3%). No differences were observed in any cancer-related end points or in actinic keratosis counts. The only quality of life difference was worse symptoms in the tretinoin group at 12 months after randomization. This trial in high-risk patients demonstrates that high-dose topical tretinoin is ineffective at reducing risk of KCs.

PKCepsilon overexpression, irrespective of genetic background, sensitizes skin to UVR-induced development of squamous-cell carcinomas.

PubMed

Sand, Jordan M; Aziz, Moammir H; Dreckschmidt, Nancy E; Havighurst, Thomas C; Kim, KyungMann; Oberley, Terry D; Verma, Ajit K

2010-01-01

Chronic exposure to UVR is the major etiologic factor in the development of human skin cancers including squamous-cell carcinoma (SCC). We have previously shown that protein Kinase C epsilon (PKCepsilon) transgenic mice on FVB/N background, which overexpress PKCepsilon protein approximately eightfold over endogenous levels in epidermis, exhibit about threefold more sensitivity than wild-type littermates to UVR-induced development of SCC. To determine whether it is PKCepsilon and not the mouse genetic background that determines susceptibility to UVR carcinogenesis, we cross-bred PKCepsilon FVB/N transgenic mice with SKH-1 hairless mice to generate PKCepsilon-overexpressing SKH-1 hairless mice. To evaluate the susceptibility of PKCepsilon SKH-1 hairless transgenic mice to UVR carcinogenesis, the mice were exposed to UVR (1-2 KJ m(-2)) three times weekly from a bank of six kodacel-filtered FS40 sunlamps. As compared with the wild-type hairless mice, PKCepsilon overexpression in SKH-1 hairless mice decreased the latency (12 weeks), whereas it increased the incidence (twofold) and multiplicity (fourfold) of SCC. The SKH hairless transgenic mice were observed to be as sensitive as FVB/N transgenic mice to UVR-induced development of SCC and expression of proliferative markers (proliferating cell nuclear antigen, signal transducers and activators of transcription 3, and extracellular signal-regulated kinase 1/2). The results indicate that PKCepsilon level dictates susceptibility, irrespective of genetic background, to UVR carcinogenesis.

Developmental and Subcellular Organization of Single-Cell C₄ Photosynthesis in Bienertia sinuspersici Determined by Large-Scale Proteomics and cDNA Assembly from 454 DNA Sequencing.

PubMed

Offermann, Sascha; Friso, Giulia; Doroshenk, Kelly A; Sun, Qi; Sharpe, Richard M; Okita, Thomas W; Wimmer, Diana; Edwards, Gerald E; van Wijk, Klaas J

2015-05-01

Kranz C4 species strictly depend on separation of primary and secondary carbon fixation reactions in different cell types. In contrast, the single-cell C4 (SCC4) species Bienertia sinuspersici utilizes intracellular compartmentation including two physiologically and biochemically different chloroplast types; however, information on identity, localization, and induction of proteins required for this SCC4 system is currently very limited. In this study, we determined the distribution of photosynthesis-related proteins and the induction of the C4 system during development by label-free proteomics of subcellular fractions and leaves of different developmental stages. This was enabled by inferring a protein sequence database from 454 sequencing of Bienertia cDNAs. Large-scale proteome rearrangements were observed as C4 photosynthesis developed during leaf maturation. The proteomes of the two chloroplasts are different with differential accumulation of linear and cyclic electron transport components, primary and secondary carbon fixation reactions, and a triose-phosphate shuttle that is shared between the two chloroplast types. This differential protein distribution pattern suggests the presence of a mRNA or protein-sorting mechanism for nuclear-encoded, chloroplast-targeted proteins in SCC4 species. The combined information was used to provide a comprehensive model for NAD-ME type carbon fixation in SCC4 species.

Altered β-catenin expression related to cancer progression on actinic cheilitis and squamous cell carcinoma of the lip.

PubMed

Schussel, Juliana L; Pinto, Décio Dos Santos; Martins, Marília Trierveiler

2011-02-01

β-Catenin is a bifunctional protein related to cell adhesion and gene transcription when activated by Wnt pathway. Altered expression of β-catenin was related to loss of differentiation, more aggressive phenotype, increase of tumor invasion, and poor prognosis in a number of different cancers. Actinic cheilitis is caused by excessive exposure to ultraviolet radiation and has a high potential to suffer malignant transformation into squamous cell carcinoma (SCC) of the lip, the most frequent oral malignancy. Studies of oral cancer have shown the correlation of β-catenin expression and oral SCC prognosis, and loss of membrane expression may be considered as a potential marker for early tumor recurrence. Thirty-five cases of actinic cheilitis and 12 cases of SCC of the lip were select and submitted to immunohistochemical staining using β-catenin antibody. β-Catenin was positive on the membrane for all cases. Eighty-five percent of actinic cheilitis cases showed cytoplasmatic staining, and 22% nuclear staining. Eighty-three percent of SCC was positive for β-catenin, and none of them had nuclear staining. Cytoplasmatic and nuclear staining of β-catenin on studied cases point to pathway alterations. Results demonstrated that β-catenin expression is altered on epithelial dysplasia, and it is related to degree of alterations. Copyright © 2011 Elsevier Inc. All rights reserved.

Feasibility of utilising an infrared-thermographic technique for early detection of subclinical mastitis in dairy camels (Camelus dromedarius).

PubMed

Samara, Emad M; Ayadi, Moez; Aljumaah, Riyadh S

2014-02-01

Despite the proven ability of infrared thermography (IRT) technology for early detection of subclinical mastitis in dairy cows/sheep/goats, studies on its diagnostic feasibility in dairy camels are lacking. Sixty-five lactating camels in mid lactation, machine milked twice-daily and managed under intensive conditions were screened to evaluate the feasibility of utilising IRT compared with other routine indicators in detecting subclinical mastitis. Immediately before the morning milking, a portable infrared camera was used to obtain thermograms in duplicate for the front and rear left quarters to determine the udder surface temperature (UST). Thereafter, milk samples from quarters were collected, and processed for California mastitis test (CMT) score and somatic cell count (SCC). In the present study, CMT score was used to define subclinical mastitis and the feasibility of IRT to detect subclinical mastitis was compared with CMT and SCC. According to CMT score, subclinical mastitic udders had an average UST of 1·42 °C greater (P<0·0001) than healthy udders. The relationship between UST and CMT was found to be highly correlated (r=0·77; P<0·001), and UST was linearly increased as the CMT increased [UST (°C)=34·86+0·66×CMT score; R 2=0·65; P<0·001]. Additionally, high correlations were obtained between UST and SCC score (r=0·75; P<0·001) and the relationship between UST and SCC was fitted best to a logarithmic equation [UST, °C=33·39+0·88×Log (SCC, ×103 cells/ml), R 2=0·61, P<0·001]. The cut-off value, sensitivity, specificity and area under the receiver operating characteristics (ROC) curve for UST were 35·15 °C, 0·90, 0·98, and 0·95, respectively, when subclinical mastitis was defined according to CMT score, and were 35·70 °C, 0·89, 0·96 and 0·94, respectively, when categorised according to the obtained SCC threshold (SCC=432 000 cells/ml). In conclusion, IRT, as an indirect non-invasive screening method, was highly feasible for distinguishing subclinical mastitic udders in dairy camels, which is crucial to treat mastitis early and efficiently.

Small cell carcinoma of rectum: A case report

PubMed Central

Ihtiyar, Enver; Algin, Cem; Isiksoy, Serap; Ates, Ersin

2005-01-01

We present a case of a 40-year-old woman with small-cell carcinoma (SCC) of the rectum. She had profuse bleeding in rectum for 5 d. By colonoscopy, polyps were determined in the rectum and biopsies were carried out. Histopathologically, the polyps were adenomatous. Because of the profuse bleeding in rectum, she underwent low anterior resection. After the diagnosis of SCC, she received intravenous chemotherapy with standard doses of siklofosfamid, adriamycin, and vepesid. Nevertheless, intracranial metastases were revealed and she died 6 mo after the operation. PMID:15918209

Non-invasive imaging of actinic cheilitis and squamous cell carcinoma of the lip.

PubMed

Lupu, Mihai; Caruntu, Ana; Caruntu, Constantin; Boda, Daniel; Moraru, Liliana; Voiculescu, Vlad; Bastian, Alexandra

2018-05-01

An early diagnosis is of overwhelming importance for the management and prognosis of mucocutaneous cancer. Actinic cheilitis (AC), defined by the clonal expansion of genomically unstable keratinocytes, is the most common potentially malignant lesion affecting the lips. Squamous cell carcinoma (SCC) is the most frequent oral malignancy, and there is strong evidence that the majority of the SCCs of the lip originate from AC. There is considerable difficulty in discerning between dysplasia and invasive carcinomas solely on a clinical basis. Although dermoscopy has become an essential tool for skin tumor evaluation, reflectance confocal microscopy (RCM) is a non-invasive imaging technology that has proved itself extremely useful in the diagnosis and monitoring of several skin diseases, including AC and SCC. The present study aimed to re-emphasize the usefulness of RCM in the early detection of malignant transformation, using AC and SCC of the lips as working examples. Due to the apparent innocuousness of AC for numerous patients, it is not possible to overstress the importance of a correct and early diagnosis, proper treatment and long-term patient follow-up as being essential for preventing the progression to lip SCC, or for its timely diagnosis.

Lymph node ratio as a prognostic factor in metastatic cutaneous head and neck squamous cell carcinoma.

PubMed

Vasan, Kartik; Low, Tsu-Hui Hubert; Gupta, Ruta; Ashford, Bruce; Asher, Rebecca; Gao, Kan; Ch'ng, Sydney; Palme, Carsten E; Clark, Jonathan R

2018-05-01

The prognostic impact of the size and number of nodal metastases in head and neck cutaneous squamous cell carcinoma (SCC) is well established. The purpose of this study was to validate the prognostic significance of the lymph node ratio in metastatic head and neck cutaneous SCC. A retrospective review of 326 patients with head and neck cutaneous SCC with parotid and/or cervical nodal metastases was performed. The primary endpoints were overall survival (OS) and disease-free survival (DFS). The minimal-P approach was used to investigate the optimal lymph node ratio threshold. Our data included 77 recurrences and 101 deaths. A lymph node ratio of 6% was a significant predictor of shorter DFS (hazard ratio [HR] 1.62; 95% confidence interval [CI] 1.11-2.38; P = .01) and OS (HR 1.63; 95% CI 1.03-2.58; P = 0.04) on multivariable analysis. The lymph node ratio is an independent prognosticator of survival outcomes in patients presenting with metastatic head and neck cutaneous SCC. A lymph node ratio >6% is a significant threshold to categorize patients into low and high risk. © 2018 Wiley Periodicals, Inc.

Non-invasive imaging of actinic cheilitis and squamous cell carcinoma of the lip

PubMed Central

Lupu, Mihai; Caruntu, Ana; Caruntu, Constantin; Boda, Daniel; Moraru, Liliana; Voiculescu, Vlad; Bastian, Alexandra

2018-01-01

An early diagnosis is of overwhelming importance for the management and prognosis of mucocutaneous cancer. Actinic cheilitis (AC), defined by the clonal expansion of genomically unstable keratinocytes, is the most common potentially malignant lesion affecting the lips. Squamous cell carcinoma (SCC) is the most frequent oral malignancy, and there is strong evidence that the majority of the SCCs of the lip originate from AC. There is considerable difficulty in discerning between dysplasia and invasive carcinomas solely on a clinical basis. Although dermoscopy has become an essential tool for skin tumor evaluation, reflectance confocal microscopy (RCM) is a non-invasive imaging technology that has proved itself extremely useful in the diagnosis and monitoring of several skin diseases, including AC and SCC. The present study aimed to re-emphasize the usefulness of RCM in the early detection of malignant transformation, using AC and SCC of the lips as working examples. Due to the apparent innocuousness of AC for numerous patients, it is not possible to overstress the importance of a correct and early diagnosis, proper treatment and long-term patient follow-up as being essential for preventing the progression to lip SCC, or for its timely diagnosis. PMID:29725529

Treatment of naturally occuring hemangiopericytoma and oral squamous cell carcinoma in dogs using surgery and photodynamic therapy with HPPH as a photosensitizer

NASA Astrophysics Data System (ADS)

Payne, John T.; McCaw, Dudley L.; Rogers, Kevin J.; Tompson, Robert V.

1995-05-01

Pyropheophorbide-a-hexyl ether (HPPH) is a new photosensitizer for use with photodynamic therapy (PDT) that has shown promise in laboratory animals. PDT, using this drug, is being used to treat canine patients afflicted with hemangiopericytoma and oral squamous cell carcinoma (SCC) at the University of Missouri-Columbia College of Veterinary Medicine. To date, 11 dogs with hemangiopericytoma and 5 dogs with oral SCC have been treated using a combination of surgery and PDT. Thus far, there have been no serious complications attributable to the treatment. Two dogs have had recurrences of the hemangiopericytoma and there have been no recurrences of SCC with a median follow time of 5 months. Both recurrent hemangiopericytomas were in patients with large tumors that had previous surgery. This study is ongoing and no conclusions have been reached; however several observations are noted. It appears that PDT using HPPH is safe is dogs, and may decrease the recurrence rate of Hemangiopericytomas. In dogs with oral SCC, the treatment is effective is causing necrosis and sloughing of the tumor tissue, and recurrences have not been noted on follow-ups up to 6 months.

Surgical management for squamous cell carcinoma of vulva

PubMed Central

Amavi, Ayi Kossigan; Kouadio, Laurent; Adabra, Komlan; Tengue, Kodjo; Tijami, Fouad; Jalil, Abdelouahed

2016-01-01

To analyze our surgical management and the result of squamous cell carcinoma (SCC) of vulva. Retrospectively, we collected 38 cases of SCC; 17 cases of them were early SCC and 21 cases were locally advanced. The patients underwent primary surgery. The survival was estimated using Kaplan-Meier analysis and the log rank test. The mean age was 60.78 years. Total vulvectomy was performed in all patients. Superficial and deep incision of bilateral inguinal lymphadenectomy was performed by separates incisions for SCC infiltrating more than 1mm. The average tumor size was 53 mm (10 to 140mm). Morbidity was 42.1%. Lateral resection margin ≥8mm was obtained in 57.1%. Eighteen patients benefited from adjuvant radiotherapy. The follow-up median was 19.4 months (6 to 61.5 month) with 05 recurrences in 12 months. The survival using the Kaplan-Meyer analysis at 5 years, was 62.1% (71.2%N- vs 46.7%N+; p = 0.13). We identified two groups for locally advanced vulva cancer. Primary surgery keeps its place. Neo adjuvant radio chemotherapy followed by surgery is the alternative treatment for locally extensive lesions. PMID:27642483

Local and Regional Spread of Primary Conjunctival Squamous Cell Carcinoma.

PubMed

Desai, Shilpa J; Pruzan, Noelle L; Geske, Michael J; Jeng, Bennie H; Bloomer, Michele M; Vagefi, M Reza

2016-04-06

Two cases of biopsy-proven conjunctival squamous cell carcinoma (SCC) that developed local and regional spread are described. The cases involved a 65-year-old woman and a 79-year-old man who were initially treated at outside institutions for SCC of the conjunctiva. The patients did not have a history of immune compromise. The female patient presented with direct extension into the lacrimal gland but deferred recommended exenteration. Despite eventual exenteration, she developed metastasis to a neck node 6 months later, which was treated with radiotherapy. The male patient presented with local recurrence and a parotid node metastasis treated with exenteration, parotidectomy, selective neck dissection, and postoperative radiotherapy. Review of the outside pathology of both cases revealed positive tumor margins at the time of original resection. Local control of conjunctival SCC is of critical importance to reduce the risk of orbital extension and regional spread.

Metabolic Profile of Oral Squamous Carcinoma Cell Lines Relies on a Higher Demand of Lipid Metabolism in Metastatic Cells

PubMed Central

Sant’Anna-Silva, Ana Carolina B.; Santos, Gilson C.; Campos, Samir P. Costa; Oliveira Gomes, André Marco; Pérez-Valencia, Juan Alberto; Rumjanek, Franklin David

2018-01-01

Tumor cells are subjected to a broad range of selective pressures. As a result of the imposed stress, subpopulations of surviving cells exhibit individual biochemical phenotypes that reflect metabolic reprograming. The present work aimed at investigating metabolic parameters of cells displaying increasing degrees of metastatic potential. The metabolites present in cell extracts fraction of tongue fibroblasts and of cell lines derived from human tongue squamous cell carcinoma lineages displaying increasing metastatic potential (SCC9 ZsG, LN1 and LN2) were analyzed by 1H NMR (nuclear magnetic resonance) spectroscopy. Living, intact cells were also examined by the non-invasive method of fluorescence lifetime imaging microscopy (FLIM) based on the auto fluorescence of endogenous NADH. The cell lines reproducibly exhibited distinct metabolic profiles confirmed by Partial Least-Square Discriminant Analysis (PLS-DA) of the spectra. Measurement of endogenous free and bound NAD(P)H relative concentrations in the intact cell lines showed that ZsG and LN1 cells displayed high heterogeneity in the energy metabolism, indicating that the cells would oscillate between glycolysis and oxidative metabolism depending on the microenvironment’s composition. However, LN2 cells appeared to have more contributions to the oxidative status, displaying a lower NAD(P)H free/bound ratio. Functional experiments of energy metabolism, mitochondrial physiology, and proliferation assays revealed that all lineages exhibited similar energy features, although resorting to different bioenergetics strategies to face metabolic demands. These differentiated functions may also promote metastasis. We propose that lipid metabolism is related to the increased invasiveness as a result of the accumulation of malonate, methyl malonic acid, n-acetyl and unsaturated fatty acids (CH2)n in parallel with the metastatic potential progression, thus suggesting that the NAD(P)H reflected the lipid catabolic/anabolic pathways. PMID:29456966

Primary Endometrial Squamous Cell Carcinoma In Situ: Report of a rare disease.

PubMed

Jetley, Sujata; Jairajpuri, Zeeba S; Hassan, Mohammad J; Madaan, Garima; Jain, Reena

2015-11-01

Squamous cell carcinoma (SCC) of the endometrium, whether primary or secondary to cervical cancer, is a rare entity. Primary endometrial squamous cell carcinoma in situ is even more uncommon; it usually occurs in postmenopausal women and has a strong association with pyometra. We report a 60-year-old multiparous postmenopausal woman who presented to the Hakeem Abdul Hameed Centenary Hospital, New Delhi, India, in May 2014 with a lower abdominal swelling corresponding in size to a pregnancy of 26 gestational weeks and vaginal discharge of one year's duration. A total abdominal hysterectomy with a bilateral salpingooophorectomy was performed, which revealed an enlarged uterus with pyometra. Histopathology showed that the entire endometrial lining had been replaced with malignant squamous cells without invasion of the myometrium. Immunohistochemistry revealed that the tumour cells were positive for p63 with a high Ki-67 labelling index. No adjuvant therapy was required and the patient was disease-free at a seven-month follow-up.

Comparison of risk patterns in carcinoma and melanoma of the skin in men: a multi-centre case–case–control study

PubMed Central

Zanetti, R; Rosso, S; Martinez, C; Nieto, A; Miranda, A; Mercier, M; Loria, D I; Østerlind, A; Greinert, R; Navarro, C; Fabbrocini, G; Barbera, C; Sancho-Garnier, H; Gafà, L; Chiarugi, A; Mossotti, R

2006-01-01

We directly compared risk factors between 214 histologically confirmed melanomas (CMM), 215 basal-cell carcinomas (BCC) and 139 squamous-cell carcinomas (SCC) in a multiple case–case–control study with 349 controls from patients without dermatological disease admitted to the same hospitals. Subjects with fair hair had a significant risk increase for all types of tumours at a comparable level (ORadj for blonde hair: CMM 2.3; SCC 2.4; BCC 2.3). The effect of pale eyes was significant and similar for CMM and BCC (ORadj 2.6). Intermittent sun exposure measured in hours spent at beach during holidays was significant for both CMM (ORadj 2.6 for more than 7000 lifelong hours) and BCC (ORadj 2.1 for more than 7000 lifelong hours), while SCC exhibited a significant risk increase for chronic exposure to sunlight measured in hours of outdoor work (ORadj 2.2 for more than 6000 lifelong hours). In the case–case comparison using a multinomial logistic regression model, we found a statistically significant risk difference for pale eyes, and number of naevi in the CMM group, compared to other skin cancers. For intermittent sun exposure, there was a significant risk difference of BCC when compared to the risk of SCC. Factors influencing risk of SCC are different, with chronic exposure to sun playing a major role in causing this type of carcinoma. PMID:16495934

Acid sphingomyelinase activity as an indicator of the cell stress in HPV-positive and HPV-negative head and neck squamous cell carcinoma.

PubMed

Gerle, Mirko; Medina, Tuula Peñate; Gülses, Aydin; Chu, Hanwen; Naujokat, Hendrik; Wiltfang, Jörg; Açil, Yahya

2018-03-21

Human papillomavirus (HPV) infection, especially HPV-16 and HPV-18, has been increasingly associated with head and neck squamous cell carcinoma. The treatment of HPV-positive squamous cell carcinoma has a better response to both radiotherapy and chemotherapy and presents a better prognosis for the patient. Defining the underlying mechanism of the difference might help in developing future treatment options and could be an important factor in personal therapy planning. Endogenously secreted acid sphingomyelinase (ASMase) levels in the cellular stress caused by irradiation and cisplatin were investigated. MTT assay was performed to evaluate the viability of the treated cells. Keratinocytes were used to evaluate the effects of radiation on normal tissues. Irradiation caused a dose-dependent increase in ASMase activity in both SCC9 HPV-negative, and UDSCC2 HPV-positive cells. ASMase activity in UDSCC2 cells was significantly higher than that in SCC9 cells. UDSCC cells were more sensitive to cisplatin treatment than SCC cells, and the dose-response in the activity was observed in long-time treatments when high doses of cisplatin were used. The results of the current study have clearly showed that HPV positivity should be considered as one of the determinative factors which should be considered when tumor treatments are planned. However, further studies are needed to determine the differences in cellular responses and pathways among HPV-negative and HPV-positive cells.

DEVELOPMENT OF AN EMAT IN-LINE INSPECTION SYSTEM FOR DETECTION, DISCRIMINATION, AND GRADING OF STRESS CORROSION CRACKING IN PIPELINES

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jeff Aron; Jeff Jia; Bruce Vance

2005-02-01

This report describes prototypes, measurements, and results for a project to develop a prototype pipeline in-line inspection (ILI) tool that uses electromagnetic acoustic transducers (EMATs) to detect and grade stress corrosion cracking (SCC). The introduction briefly provides motivation and describes SCC, gives some background on EMATs and guided ultrasonic waves, and reviews promising results of a previous project using EMATs for SCC. The experimental section then describes lab measurement techniques and equipment, the lab mouse and prototypes for a mule, and scan measurements made on SCC. The mouse was a moveable and compact EMAT setup. The prototypes were even moremore » compact circuits intended to be pulled or used in an ILI tool. The purpose of the measurements was to determine the best modes, transduction, and processing to use, to characterize the transducers, and to prove EMATs and mule components could produce useful results. Next, the results section summarizes the measurements and describes the mouse scans, processing, prototype circuit operating parameters, and performance for SH0 scans. Results are given in terms of specifications--like SNR, power, insertion loss--and parametric curves--such as signal amplitude versus magnetic bias or standoff, reflection or transmission coefficients versus crack depth. Initially, lab results indicated magnetostrictive transducers using both SH0 and SV1 modes would be worthwhile to pursue in a practical ILI system. However, work with mule components showed that SV1 would be too dispersive, so SV1 was abandoned. The results showed that reflection measurements, when normalized by the direct arrival are sensitive to and correlated with SCC. This was not true for transmission measurements. Processing yields a high data reduction, almost 60 to 1, and permits A and C scan display techniques and software already in use for pipeline inspection. An analysis of actual SH0 scan results for SCC of known dimensions showed that length and depth could be determined for deep enough cracks. Defect shadow and short length effects were apparent but may be taken into account. The SH0 scan was done with the mule prototype circuits and permanent magnet EMATs. These gave good enough results that this hardware and the processing techniques are very encouraging for use in a practical ILI tool.« less

Integrated molecular portrait of non-small cell lung cancers

PubMed Central

2013-01-01

Background Non-small cell lung cancer (NSCLC), a leading cause of cancer deaths, represents a heterogeneous group of neoplasms, mostly comprising squamous cell carcinoma (SCC), adenocarcinoma (AC) and large-cell carcinoma (LCC). The objectives of this study were to utilize integrated genomic data including copy-number alteration, mRNA, microRNA expression and candidate-gene full sequencing data to characterize the molecular distinctions between AC and SCC. Methods Comparative genomic hybridization followed by mutational analysis, gene expression and miRNA microarray profiling were performed on 123 paired tumor and non-tumor tissue samples from patients with NSCLC. Results At DNA, mRNA and miRNA levels we could identify molecular markers that discriminated significantly between the various histopathological entities of NSCLC. We identified 34 genomic clusters using aCGH data; several genes exhibited a different profile of aberrations between AC and SCC, including PIK3CA, SOX2, THPO, TP63, PDGFB genes. Gene expression profiling analysis identified SPP1, CTHRC1and GREM1 as potential biomarkers for early diagnosis of the cancer, and SPINK1 and BMP7 to distinguish between AC and SCC in small biopsies or in blood samples. Using integrated genomics approach we found in recurrently altered regions a list of three potential driver genes, MRPS22, NDRG1 and RNF7, which were consistently over-expressed in amplified regions, had wide-spread correlation with an average of ~800 genes throughout the genome and highly associated with histological types. Using a network enrichment analysis, the targets of these potential drivers were seen to be involved in DNA replication, cell cycle, mismatch repair, p53 signalling pathway and other lung cancer related signalling pathways, and many immunological pathways. Furthermore, we also identified one potential driver miRNA hsa-miR-944. Conclusions Integrated molecular characterization of AC and SCC helped identify clinically relevant markers and potential drivers, which are recurrent and stable changes at DNA level that have functional implications at RNA level and have strong association with histological subtypes. PMID:24299561

Evaluation of Hypoxia Inducible Factor-1α and Glucose Transporter-1 Expression in Non Melanoma Skin Cancer: An Immunohistochemical Study

PubMed Central

Seleit, Iman; Bakry, Ola Ahmed; Ragab, Rania Abdel Aziz; Al-Shiemy, shimaa Ahmed

2017-01-01

Introduction Hypoxia Inducible Factor-1 (HIF-1) is a mediator enabling cell adaptation to hypoxia. It plays its role mainly through transcription of many target genes including Glucose Transporter-1 (GLUT-1) gene. Aim The present work aimed at evaluating the pattern and distribution of HIF-1α and GLUT-1 in each case and control. Materials and Methods A case-control and retrospective study was conducted on archival blocks diagnosed from pathology department as, Basal Cell Carcinoma (BCC, 20 cases), cutaneous Squamous Cell Carcinoma (SCC, 20 cases) and 20 normal site-matched skin biopsies from age and gender-matched healthy subjects as a control. Evaluation of both HIF-1α and GLUT1 expression using standard immunohistochemical techniques was performed on cut sections from selected paraffin embedded blocks. Results HIF-1α was expressed in 90%, 35% and 100% of normal skin, BCC and SCC tumour islands respectively. It was up regulated in both BCC and SCC compared with normal skin (p= 0.001, p<0.001 respectively). GLUT-1 was expressed in 100%, 70% and 100% of normal skin, BCC and SCC tumour islands respectively. It was down regulated in Non Melanoma Skin Cancer (NMSC) cases compared with normal skin (p=0.004). HIF-1α and GLUT-1 localization in tumour nests was central, peripheral or central and peripheral. Both HIF-1α and GLUT-1 showed variable expression in stroma, adnexa and inflammatory cells. No significant correlation was found between Histo (H) score or expression percentage values of HIF-1α and those of GLUT-1 in tumour islands or in overlying epidermis either in BCC or SCC. Conclusion HIF-1α may have a role in NMSC pathogenesis through adaptation to hypoxia which results from excessive proliferation. GLUT-1 down regulation in NMSC may be explained by its consumption by proliferating tumour cells. The expression of HIF-1α and GLUT-1 in normal epidermis, stromal and adnexal structures needs further research. PMID:28764171

Primary epidermoid carcinoma of the breast presenting as a breast abscess and sepsis.

PubMed

Damin, Andrea Pires; Nascimento, Fernanda Costa; Andreola, João Batista; Cerutti, Talita Haubert; Roehe, Adriana; Damin, Daniel Carvalho

2011-12-01

Squamous cell carcinoma (SCC) of the breast is an extremely rare form of cancer, accounting for approximately 0.04% of all malignant breast tumors. To date, only a limited number of cases of SCC of the breast have been reported, and most of them presented like the usual breast carcinomas. A 39-year-old woman presented with a large breast abscess and signs of sepsis. After surgical debridement of the lesion, histopathological examination of the abscess capsule revealed the presence of SCC of the breast. The definitive treatment for the tumor consisted of modified radical mastectomy with resection of the residual lesion in the right breast. This unusual case illustrates how an apparently benign disorder such as a breast abscess might be related to a clinically occult malignancy. A review of the literature on SCC of the breast is presented.

Personal history of psoriasis and risk of nonmelanoma skin cancer (NMSC) among women in the United States: A population-based cohort study.

PubMed

Dai, Hongji; Li, Wen-Qing; Qureshi, Abrar A; Han, Jiali

2016-10-01

To our knowledge, no prospective studies have examined the association between personal history of psoriasis and risk of nonmelanoma skin cancer. We sought to examine this association based on 2 prospective cohorts, the Nurses' Health Study and Nurses' Health Study II. Diagnoses of nonmelanoma skin cancer, including basal cell carcinoma and squamous cell carcinoma (SCC), were obtained by self-reported questionnaires. Information on clinician-diagnosed psoriasis and diagnosis year was collected and validated with a supplementary questionnaire. After 2,487,941 and 2,478,148 person-years of follow-up, we documented 1725 SCC cases and 16,075 basal cell carcinoma cases, respectively. For the combined cohorts, personal history of psoriasis was associated with an elevated risk of SCC, with a multivariate-adjusted relative risk (RR) of 1.51 (95% confidence interval [CI] 1.11-2.05). The associations appeared stronger with increasing psoriasis severity, with RR of 1.42 (95% CI 0.94-2.15) in the mild psoriasis group and RR of 1.99 (95% CI 0.74-5.32) in the moderate to severe psoriasis group (P trend = .03). There was no association between psoriasis and the risk of basal cell carcinoma (RR 0.95; 95% CI 0.75-1.18). Lack of treatment data may bias the result. Personal history of psoriasis may be associated with an increased risk of SCC. Further investigations are warranted to understand the underlying mechanisms. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Cigarette Smoking and the Risks of Basal Cell Carcinoma and Squamous Cell Carcinoma.

PubMed

Dusingize, Jean Claude; Olsen, Catherine M; Pandeya, Nirmala P; Subramaniam, Padmini; Thompson, Bridie S; Neale, Rachel E; Green, Adèle C; Whiteman, David C

2017-08-01

Sunlight is the principal environmental risk factor for keratinocyte cancers, but other carcinogens have also been implicated, including tobacco smoke. Findings have been conflicting, however. We investigated associations between cigarette smoking and incidence of basal cell carcinoma (BCC) or squamous cell carcinoma (SCC) in QSkin, a prospective study of skin cancer (N = 43,794). Smoking history was self-reported at baseline; newly diagnosed BCCs and SCCs were ascertained through data linkage and verified by histopathology reports. We restricted analyses to white participants who at baseline reported no past history of skin cancer excisions and no more than five destructively treated actinic skin lesions. We fitted Cox proportional hazards models, adjusted for known confounders. Compared with never smokers, current smokers had significantly lower risks of BCC (hazard ratio = 0.6; 95% confidence interval = 0.4-0.9) but significantly higher risks of SCC (hazard ratio = 2.3; 95% confidence interval = 1.5-3.6). Former smokers had similar risks for BCC and SCC as never smokers. Among smokers, we observed no dose-response trends with duration of smoking, intensity, or time since quitting. On further analysis, current smokers had fewer skin examinations and procedures than never smokers, suggesting greater opportunities for detection among never smokers. Strengths include large sample size, prospective design, and virtually complete follow-up; however, histologic details were missing for a proportion of excised tumors. In conclusion, current smokers had a lower incidence of BCC (possibly because of detection bias) but higher rates of SCC. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Identification of Logic Relationships between Genes and Subtypes of Non-Small Cell Lung Cancer

PubMed Central

Su, Yansen; Pan, Linqiang

2014-01-01

Non-small cell lung cancer (NSCLC) has two major subtypes: adenocarcinoma (AC) and squamous cell carcinoma (SCC). The diagnosis and treatment of NSCLC are hindered by the limited knowledge about the pathogenesis mechanisms of subtypes of NSCLC. It is necessary to research the molecular mechanisms related with AC and SCC. In this work, we improved the logic analysis algorithm to mine the sufficient and necessary conditions for the presence states (presence or absence) of phenotypes. We applied our method to AC and SCC specimens, and identified lower and higher logic relationships between genes and two subtypes of NSCLC. The discovered relationships were independent of specimens selected, and their significance was validated by statistic test. Compared with the two earlier methods (the non-negative matrix factorization method and the relevance analysis method), the current method outperformed these methods in the recall rate and classification accuracy on NSCLC and normal specimens. We obtained biomarkers. Among biomarkers, genes have been used to distinguish AC from SCC in practice, and other six genes were newly discovered biomarkers for distinguishing subtypes. Furthermore, NKX2-1 has been considered as a molecular target for the targeted therapy of AC, and other genes may be novel molecular targets. By gene ontology analysis, we found that two biological processes (‘epidermis development’ and ‘cell adhesion’) were closely related with the tumorigenesis of subtypes of NSCLC. More generally, the current method could be extended to other complex diseases for distinguishing subtypes and detecting the molecular targets for targeted therapy. PMID:24743794

Basaloid squamous cell carcinoma of the esophagus.

PubMed

Chen, Shao-Bin; Weng, Hong-Rui; Wang, Geng; Yang, Jie-Sheng; Yang, Wei-Ping; Li, Hua; Liu, Di-Tian; Chen, Yu-Ping

2012-07-01

Basaloid squamous cell carcinoma (BSCC) of the esophagus is a rare carcinoma with distinct characteristics. No standard treatment has been established. This retrospective study was designed to investigate the clinical and pathological characteristics, diagnosis, treatment, and prognosis of esophageal BSCC. Clinical data were retrospectively analyzed from 26 patients with pathologically confirmed esophageal BSCC who underwent transthoracic esophagectomy with lymphadenectomy between January 1995 and June 2010 at the Cancer Hospital of Shantou University Medical College. Clinicopathologic data between BSCC patients and different histologic grades of esophageal squamous cell carcinoma (ESCC) patients were statistically compared by means of the χ(2) test or Fisher's exact test. The Kaplan-Meier and log-rank methods were used to estimate and compare survival rates. Microscopically, BSCC was characterized by a nesting, lobular, or trabecular arrangement of small crowded cells with scant cytoplasm. None of the histologic specimens taken at preoperative esophagoscopy were diagnosed as BSCC. The median survival time (MST) of the 26 patients was 29.0 months (95% confidence interval, 9.0-49.0), and the 1-, 3-, and 5-year overall survival rates were 73.1, 42.7, and 36.6%, respectively. The MST for BSCC patients was significantly lower than that of well-differentiated SCC patients (P = 0.024), but there were no significant differences between the MST for BSCC patients and that of moderately or poorly differentiated SCC patients (P > 0.05). BSCC of the esophagus is a rare but distinctive disease and is prone to be misdiagnosed by endoscopic biopsy. The prognosis is poorer than well-differentiated SCC, but similar to moderately or poorly differentiated SCC.

Relevance of psychosocial factors to quality of life in oral cancer and oral lichen planus: a prospective comparative study.

PubMed

Rana, Madiha; Kanatas, Anastasios; Herzberg, Philipp Y; Gellrich, Nils-Claudius; Rana, Majeed

2015-09-01

We can improve our understanding of how patients cope with oral squamous cell carcinoma (SCC) by making a comparison with their processes of coping and those used in other conditions. We have therefore compared quality of life (QoL), severity of symptoms, coping strategies, and factors that influence coping between patients with oral SCC and those with oral lichen planus. We asked 104 patients with oral SCC and 51 with oral lichen planus to complete questionnaires about their coping strategies, social support, locus of control, spirituality, QoL, and severity of symptoms. The outcome was that patients with oral SCC were far more likely to resort to coping strategies such as depressive coping, distraction, and self-motivation. The groups also differed regarding QoL and severity of symptoms. Patients with oral SCC had a poorer QoL and higher depression scores, whereas patients with oral lichen planus had better scores in the social support and spirituality categories. Patients with oral SCC generally had more distress than those with oral lichen planus. Not only did the former resort to depressive coping strategies, but they also had poorer QoL and higher values for depression. For the patients with oral lichen planus, social support and spirituality were protective, whereas they were associated with distress by patients with oral SCC. Copyright © 2015 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Unchanging pattern of prevalence of esophageal cancer, overall and by histological subtype, in the endoscopy service of the main referral hospital in the central region of Rio Grande do Sul State, in Southern Brazil.

PubMed

Fagundes, R B; de Carli, D; Xaubet, R V; Cantarelli, J C

2016-08-01

Squamous cell carcinoma (SCC) and adenocarcinoma (ADC) are the two main histological types of esophageal cancer. Southern Brazil has the highest rates of esophageal cancer in South America, and the most prevalent subtype of esophageal cancer has been SCC. This study assessed the trend changes in the histological types of esophageal cancer, in a 20-year period, in the central region of Rio Grande do Sul State, Brazil. We searched all cases of esophageal cancer from 1993 to 2012 by their histological diagnosis, grouping the patients in 4-year time periods to evaluate time trends. Among 18 441 upper gastrointestinal endoscopies we identified 686 cases of esophageal cancer. Histological study confirmed the diagnosis of SCC in 640 (93.3%) patients and ADC in 46 (6.7%). Overall, 522 men were diagnosed with esophageal carcinoma; from these, 489 (93.6%) presented SCC, and 33 (6.3%) ADC. Among women, 164 had the diagnosis of esophageal cancer, 151 (92%) SCC, and 13 (7.9%) ADC. The proportion found among men and women was 3.1:1, respectively. The prevalence rate of esophageal cancer, along a 20 year-period, remained stable, as well as the rates of SCC and ADC. SCC was the most common type of esophageal cancer, and ADC presented very low prevalence. © 2015 International Society for Diseases of the Esophagus.

Implication of human telomerase reverse transcriptase in cervical carcinogenesis and cancer recurrence.

PubMed

Wang, P-H; Ko, J-L

2006-01-01

The objective of this study was to evaluate the implication of human telomerase reverse transcriptase (hTERT) in cervical carcinogenesis and cancer recurrence. One hundred three cases of uterine cervix, including 20 normal, 13 low-grade squamous intraepithelial lesion (LSIL), 30 high-grade squamous intraepithelial lesion (HSIL), and 40 squamous cell carcinoma (SCC) tissues, were evaluated for hTERT immunoreactivity. The expressions of hTERT in normal, LSIL, HSIL, and SCC tissues were compared by Fisher exact or Chi-square test. The relationships between hTERT and clinicopathologic variables of SCC were also assessed. Furthermore, SCC patients were subdivided into negative and positive hTERT expression subgroups, and Kaplan-Meier curves were used to plot the cumulative recurrence hazard for 5 years. There was a significant difference for hTERT expression between LSIL and HSIL subgroups (P < 0.001) but no significant difference between normal and LSIL as well as HSIL and SCC subgroups. For SCC patients, hTERT expression was positive in lymph nodes, vagina, and parametrium metastastic cases. However, it did not reach a significant difference. The cumulative recurrence hazard for 5 years was about 29% in positive hTERT expression subgroup compared to 0% in negative hTERT subgroup (P = 0.2866). In conclusion, a point stage of HSIL exists in the progression of cervical carcinogenesis when the hTERT expression increases significantly. Moreover, SCC patients with positive hTERT expression may have higher cumulative recurrence hazard.

Use of tanning devices and risk of basal cell and squamous cell skin cancers.

PubMed

Karagas, Margaret R; Stannard, Virginia A; Mott, Leila A; Slattery, Mary Jo; Spencer, Steven K; Weinstock, Martin A

2002-02-06

Use of artificial tanning devices that emit UV radiation, such as tanning lamps and tanning beds, has become increasingly popular in the United States. Although an excess risk of nonmelanoma skin cancers might be predicted from this exposure, little epidemiologic data exist. We conducted a population-based, case-control study that included 603 basal cell carcinoma (BCC) case patients, 293 squamous cell carcinoma (SCC) case patients, and 540 control subjects. Study participants were interviewed in person to obtain information on tanning device use, sun exposure history, sun sensitivity, and other risk factors for skin cancer. Overall, any use of tanning devices was associated with odds ratios of 2.5 (95% confidence interval [CI] = 1.7 to 3.8) for SCC and 1.5 (95% CI = 1.1 to 2.1) for BCC. Adjustment for history of sunburns, sunbathing, and sun exposure did not affect our results. Our findings suggest that the use of tanning devices may contribute to the incidence of nonmelanoma skin cancers. They highlight the need to further evaluate the potential risks of BCC and SCC that are associated with tanning lamp exposure and the appropriate public health response.

Primary squamous cell carcinoma of the breast with unusual basal-HER2 phenotype.

PubMed

Shui, Ruohong; Li, Anqi; Yang, Fei; Zhou, Xiaoyan; Yu, Baohua; Xu, Xiaoli; Yang, Wentao

2014-01-01

To report three cases of primary squamous cell carcinoma of the breast with an unusual "basal-HER2" phenotype. Clinical data were analyzed. Morphological features were observed. Immunohistochemical study for ER, PR, HER2, Ki-67, CK 5/6, CK10/13, CK14, EGFR, P63 and FISH detection of HER2 gene amplification were performed. Three patients were all female with 26, 57 and 66 years old. The tumors were 3 cm, 4 cm and 5 cm in size respectively. Morphologically, all three tumors were pure squamous cell carcinoma and entirely composed metaplastic squamous cells. Two tumors were moderately differentiated and one was poorly differentiated. All three patients were positive for P63 or CK10/13. All three tumors exhibited basal-HER2 phenotype: negative for ER and PR, positive for HER2 protein and HER2 gene amplification, and positive for at least two basal markers. SCC with basal-HER2 phenotype is an extremely rare subset of breast carcinoma. Since it may have worse prognosis than typical basal-like SCC, recognization of this unusual SCC in routine work may have obvious clinical significance.

Spindle Cell Carcinoma of Nasal Cavity- A Case Report

PubMed Central

Mittal, Abhishek; Nagpal, Tapan

2016-01-01

Spindle Cell Carcinoma (SpCC), also known as Sarcomatoid Carcinoma, is a rare and peculiar biphasic malignant neoplasm that occurs mainly in the upper aero-digestive tract, mostly in larynx. SCC accounts for 3% of all squamous cell carcinomas (SCCs) in the head and neck region. It is a rare variant of SCC which shows spindled or pleomorphic tumour cells simulating a true sarcoma. We present a case report of SpCC nasal cavity in a 50-year-old female patient, presented with intermittent epistaxis from left nasal cavity. On physical examination, the patient had an ulcero-exophytic type of mass in the left nasal cavity and a smooth bulge on the left side of anterior hard palate. Patient underwent excision of nasal mass along with partial palatectomy by facial degloving approach and reconstruction of palate with naso-labial flap. The postoperative histopathological report showed SCC. Surgery forms the mainstay of treatment. Radiotherapy and Chemotherapy is warranted in order to improve treatment results. As only few cases have been reported, we report a case of this rare entity to contribute for better understanding and awareness of this rare malignancy. PMID:27190843

Omega-3 polyunsaturated fatty acids selectively inhibit growth in neoplastic oral keratinocytes by differentially activating ERK1/2

PubMed Central

Parkinson, Eric Kenneth

2013-01-01

The long-chain omega-3 polyunsaturated fatty acids (n-3 PUFAs)—eicosapentaenoic acid (EPA) and its metabolite docosahexaenoic acid (DHA)—inhibit cancer formation in vivo, but their mechanism of action is unclear. Extracellular signal-regulated kinase 1/2 (ERK1/2) activation and inhibition have both been associated with the induction of tumour cell apoptosis by n-3 PUFAs. We show here that low doses of EPA, in particular, inhibited the growth of premalignant and malignant keratinocytes more than the growth of normal counterparts by a combination of cell cycle arrest and apoptosis. The growth inhibition of the oral squamous cell carcinoma (SCC) lines, but not normal keratinocytes, by both n-3 PUFAs was associated with epidermal growth factor receptor (EGFR) autophosphorylation, a sustained phosphorylation of ERK1/2 and its downstream target p90RSK but not with phosphorylation of the PI3 kinase target Akt. Inhibition of EGFR with either the EGFR kinase inhibitor AG1478 or an EGFR-blocking antibody inhibited ERK1/2 phosphorylation, and the blocking antibody partially antagonized growth inhibition by EPA but not by DHA. DHA generated more reactive oxygen species and activated more c-jun N-terminal kinase than EPA, potentially explaining its increased toxicity to normal keratinocytes. Our results show that, in part, EPA specifically inhibits SCC growth and development by creating a sustained signalling imbalance to amplify the EGFR/ERK/p90RSK pathway in neoplastic keratinocytes to a supraoptimal level, supporting the chemopreventive potential of EPA, whose toxicity to normal cells might be reduced further by blocking its metabolism to DHA. Furthermore, ERK1/2 phosphorylation may have potential as a biomarker of n-3 PUFA function in vivo. PMID:23892603

Prevalence of cutaneous viral infections in incident cutaneous squamous cell carcinoma detected among chronic lymphocytic leukemia and hematopoietic stem cell transplant patients.

PubMed

Hampras, Shalaka S; Locke, Frederick L; Chavez, Julio C; Patel, Nishit S; Giuliano, Anna R; Miller, Kyle; Gheit, Tarik; Tommasino, Massimo; Rollison, Dana E

2018-04-01

The role of cutaneous viral infections in the development of non-melanoma skin cancer (NMSC), including cutaneous squamous cell carcinoma (SCC), among chronic lymphocytic leukemia (CLL) and blood and marrow transplant (BMT) patients is not established. CLL (n = 977) and BMT (n = 3587) patients treated at the Moffitt Cancer Center were included in a retrospective cohort study. Human papillomavirus (HPV) and human polyomavirus (HPyV) DNA were examined in a subset of incident SCC tumors. Five-year cumulative incidence of NMSC was 1.42% in both BMT (n = 31 NMSCs) and CLL (n = 18 NMSCs) cohorts. Of the nine SCC tumors examined from each cohort, 22.2% and 33.3% were positive for viral DNA in the transplant (HPV 65, MCV) and CLL (HPV 38, HPV 15, HPyV6) cohort, respectively. Enhanced skin cancer screening of BMT/CLL patients should be conducted to better capture incident NMSCs and examine the role of viral infections in these tumors.

Analysis of clonality and HPV infection in benign, hyperplastic, premalignant, and malignant lesions of the vulvar mucosa.

PubMed

Ueda, Yutaka; Enomoto, Takayuki; Miyatake, Takashi; Shroyer, Kenneth R; Yoshizaki, Tatsuo; Kanao, Hiroyuki; Ueno, Yuko; Sun, Hongbo; Nakashima, Ryuichi; Yoshino, Kiyoshi; Kimura, Toshihiro; Haba, Tomoko; Wakasa, Kenichi; Murata, Yuji

2004-08-01

To elucidate the pathogenesis of vulvar carcinomas, we studied clonality and human papillomavirus (HPV) infection in vulvar epithelial diseases. Monoclonal composition was demonstrated in all 9 invasive tumors (squamous cell carcinoma [SCC], 6; basal cell carcinoma, 1; malignant melanoma, 2), 15 of 20 cases of vulvar intraepithelial neoplasia (VIN), 7 of 9 cases of Paget disease, 2 of 6 cases of lichen sclerosus (LS), and 2 of 3 cases of squamous cell hyperplasia (SCH); high-risk type HPV was revealed in 5 of 6 SCCs and 17 of 20 VINs. These observations might imply that a subset of cases of LS and SCH result from a neoplastic proliferation, similar to VINs but not related to infection with high-risk type HPV. In 1 case of SCC with concurrent VIN 3 in an adjacent lesion, both lesions showed the same pattern of X chromosome inactivation and the presence of HPV-16 in episomal and integrated forms, suggesting that monoclonal expansion triggered by high-risk type HPV integration is an early event for carcinogenesis of HPV-associated SCC.

Combined human papillomavirus typing and TP53 mutation analysis in distinguishing second primary tumors from lung metastases in patients with head and neck squamous cell carcinoma.

PubMed

Daher, Tamas; Tur, Mehmet Kemal; Brobeil, Alexander; Etschmann, Benjamin; Witte, Biruta; Engenhart-Cabillic, Rita; Krombach, Gabriele; Blau, Wolfgang; Grimminger, Friedrich; Seeger, Werner; Klussmann, Jens Peter; Bräuninger, Andreas; Gattenlöhner, Stefan

2018-06-01

In head and neck squamous cell carcinoma (HNSCC), the occurrence of concurrent lung malignancies poses a significant diagnostic challenge because metastatic HNSCC is difficult to discern from second primary lung squamous cell carcinoma (SCC). However, this differentiation is crucial because the recommended treatments for metastatic HNSCC and second primary lung SCC differ profoundly. We analyzed the origin of lung tumors in 32 patients with HNSCC using human papillomavirus (HPV) typing and targeted next generation sequencing of all coding exons of tumor protein 53 (TP53). Lung tumors were clearly identified as HNSCC metastases or second primary tumors in 29 patients, thus revealing that 16 patients had received incorrect diagnoses based on clinical and morphological data alone. The HPV typing and mutation analysis of all TP53 coding exons is a valuable diagnostic tool in patients with HNSCC and concurrent lung SCC, which can help to ensure that patients receive the most suitable treatment. © 2018 Wiley Periodicals, Inc.

In vitro apoptotic effects of methanol extracts of Dianthus chinensis and Acalypha australis L. targeting specificity protein 1 in human oral cancer cells.

PubMed

Shin, Ji-Ae; Kim, Jae-Jin; Choi, Eun-Sun; Shim, Jung-Hyun; Ryu, Mi Heon; Kwon, Ki Han; Park, Hee-Min; Seo, Jin-Young; Lee, Soo-Yeon; Lim, Do-Won; Cho, Nam-Pyo; Cho, Sung-Dae

2013-07-01

The aims of this study were to evaluate the apoptotic activities and molecular mechanisms of methanol extracts of Dianthus chinensis (MEDC) and Acalypha australis L. (MEAL) in human oral cancer cells. The apoptotic effects and related molecular mechanisms of MEDC and MEAL on oral cancer cells were evaluated using MTS assay, DAPI staining, immunostaining, Western blotting, and reverse transcriptase-polymerase chain reaction. Sp1 was overexpressed in oral tumor tissues compared with normal oral mucosa. Downregulation of Sp1 inhibited the growth of SCC-15 and YD-15 oral cancer cells. MEDC and MEAL inhibited cell growth and induced apoptosis in both cell lines by decreasing the expression of Sp1. In addition, treatment of cells with MEDC and MEAL decreased Mcl-1 expression, which is a downstream target of Sp1. Our results indicate that MEDC and MEAL are bioactive natural products that can potentially induce apoptosis of tumor cells that overexpress the Sp1 protein. Copyright © 2012 Wiley Periodicals, Inc.

Effects of Carbon Nanotubes in Barrier Epithelial Cells via Effects on Lipid Bilayers

NASA Astrophysics Data System (ADS)

Lewis, Shanta

Carbon nanotubes (CNTs) are one of the most common nanoparticles (NP) found in workplace air. Therefore, there is a strong chance that these NP will enter the human body. They have similar physical properties to asbestos, a known toxic material, yet there is limited evidence showing that CNTs may be hazardous to human barrier epithelia. In previous studies done in our laboratory, the effects of CNTs on the barrier function in the human airway epithelial cell line (Calu-3) were measured. Measurements were done using electrophysiology, a technique which measures both transepithelial electrical resistance (TEER), a measure of monolayer integrity, and short circuit current (SCC) which is a measure of vectorial ion transport across the cell monolayer. The research findings showed that select physiologically relevant concentrations of long single-wall (SW) and multi-wall (MW) CNTs significantly decreased the stimulated SCC of the Calu-3 cells compared to untreated cultures. Calu-3 cells showed decreases in TEER when incubated for 48 hours (h) with concentrations of MWCNT ranging from 4microg/cm2 to 0.4ng/cm2 and SWCNT ranging from 4microg/cm2 to 0.04ng/cm2. The impaired cellular function, despite sustained cell viability, led us to investigate the mechanism by which the CNTs were affecting the cell membrane. We investigated the interaction of short MWCNTs with model lipid membranes using an ion channel amplifier, Planar Bilayer Workstation. Membranes were synthesized using neutral diphytanoylphosphatidylcholine (DPhPC) and negatively charged diphytanoylphosphatidylserine (DPhPS) lipids. Gramicidin A (GA), an ion channel reporter protein, was used to measure changes in ion channel conductance due to CNT exposures. Synthetic membranes exposed to CNTs allowed bursts of currents to cross the membrane when they were added to the membrane buffer system. When added to the membrane in the presence of GA, they distorted channel formation and reduced membrane stability.

Limitations of on-site dairy farm regulatory debits as milk quality predictors.

PubMed

Borneman, Darand L; Stiegert, Kyle; Ingham, Steve

2015-03-01

In the United States, compliance with grade A raw fluid milk regulatory standards is assessed via laboratory milk quality testing and by on-site inspection of producers (farms). This study evaluated the correlation between on-site survey debits being marked and somatic cell count (SCC) or standard plate count (SPC) laboratory results for 1,301 Wisconsin grade A dairy farms in 2012. Debits recorded on the survey form were tested as predictors of laboratory results utilizing ordinary least squares regression to determine if results of the current method for on-site evaluation of grade A dairy farms accurately predict SCC and SPC test results. Such a correlation may indicate that current methods of on-site inspection serve the primary intended purpose of assuring availability of high-quality milk. A model for predicting SCC was estimated using ordinary least squares regression methods. Step-wise selected regressors of grouped debit items were able to predict SCC levels with some degree of accuracy (adjusted R2=0.1432). Specific debit items, seasonality, and farm size were the best predictors of SCC levels. The SPC data presented an analytical challenge because over 75% of the SPC observations were at or below a 25,000 cfu/mL threshold but were recorded by testing laboratories as at the threshold value. This classic censoring problem necessitated the use of a Tobit regression approach. Even with this approach, prediction of SPC values based on on-site survey criteria was much less successful (adjusted R2=0.034) and provided little support for the on-site survey system as a way to inform farmers about making improvements that would improve SPC. The lower level of correlation with SPC may indicate that factors affecting SPC are more varied and differ from those affecting SCC. Further, unobserved deficiencies in postmilking handling and storage sanitation could enhance bacterial growth and increase SPC, whereas postmilking sanitation will have no effect on SCC because somatic cells do not reproduce in stored milk. Results suggest that close examination, and perhaps redefinition, of survey debits, along with making the survey coincident with SCC and SPC sampling, could make the on-site survey a better tool for ensuring availability of high-quality milk. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Hypericin and pulsed laser therapy of squamous cell cancer in vitro.

PubMed

Bublik, Michael; Head, Christian; Benharash, Peyman; Paiva, Marcos; Eshraghi, Adrian; Kim, Taiho; Saxton, Romaine

2006-06-01

This in vitro study compares continuous wave and pulsed laser light at longer wavelengths for activation of the phototoxic drug hypericin in human cancer cells. Two-photon pulsed laser light now allows high-resolution fluorescent imaging of cancer cells and should provide deeper tissue penetration with near infrared light for improved detection as well as phototoxicity in human tumors. Cultured Seoul National University (SNU)-1 tumor cells from a squamous cell carcinoma (SCC) were incubated with hypericin before photoirradiation at four laser wavelengths. Phototoxicity of hypericin sensitized SCC cells was measured by dimethyl thiazoldiphenyl (MTT) tetrazolium bromide cell viability assays and by confocal fluorescence microscopy via 532-nm and infrared two-photon pulsed laser light. Phototoxic response increased linearly with hypericin dose of 0.1-2 microM, light exposure time of 5-120 sec, and pulsed dye laser wavelengths of 514-593 nm. Light energy delivery for 50% cell phototoxicity (LD50) response was 9 joules at 514 nm, 3 joules at 550 nm, and less than 1 joule at the 593 nm hypericin light absorption maxima. Fluorescence confocal microscopy revealed membrane and perinuclear localization of hypericin in the SNU cells with membrane damage seen after excitation with visible 532 nm continuous wave light or two-photon 700-950 nm picosecond pulsed laser irradiation. Hypericin may be a powerful tumor targetting drug when combined with pulsed laser light in patients with recurrent head and neck SCC.

Fibroblast spheroids as a model to study sustained fibroblast quiescence and their crosstalk with tumor cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Salmenperä, Pertteli, E-mail: pertteli.salmenpera@helsinki.fi; Karhemo, Piia-Riitta; Räsänen, Kati

Stromal fibroblasts have an important role in regulating tumor progression. Normal and quiescent fibroblasts have been shown to restrict and control cancer cell growth, while cancer-associated, i. e. activated fibroblasts have been shown to enhance proliferation and metastasis of cancer cells. In this study we describe generation of quiescent fibroblasts in multicellular spheroids and their effects on squamous cell carcinoma (SCC) growth in soft-agarose and xenograft models. Quiescent phenotype of fibroblasts was determined by global down-regulation of expression of genes related to cell cycle and increased expression of p27. Interestingly, microarray analysis showed that fibroblast quiescence was associated with similarmore » secretory phenotype as seen in senescence and they expressed senescence-associated-β-galactosidase. Quiescent fibroblasts spheroids also restricted the growth of RT3 SCC cells both in soft-agarose and xenograft models unlike proliferating fibroblasts. Restricted tumor growth was associated with marginally increased tumor cell senescence and cellular differentiation, showed with senescence-associated-β-galactosidase and cytokeratin 7 staining. Our results show that the fibroblasts spheroids can be used as a model to study cellular quiescence and their effects on cancer cell progression. - Highlights: • Fibroblasts acquire a sustained quiescence when grown as multicellular spheroids. • This quiescence is associated with drastic change in gene expression. • Fibroblasts spheroids secrete various inflammation-linked cytokines and chemokines. • Fibroblasts spheroids reduced growth of RT3 SCC cells in xenograft model.« less

Targeting mTOR and AREG with everolimus, sunitinib and sorafenib in HPV-positive and -negative SCC.

PubMed

Aderhold, Christoph; Faber, Anne; Umbreit, Claudia; Birk, Richard; Weiss, Christel; Sommer, Jörg Ulrich; Hörmann, Karl; Schultz, Johannes David

2015-04-01

Head and neck squamous cell carcinoma (HNSCC) is an aggressive epithelial malignancy. It is the most common neoplasm appearing in the upper aerodigestive tract and the sixth most common cancer worldwide. The five-year survival rate remains poor despite advances in surgery, radiation and chemotherapy. Furthermore, the incidence of human papillomavirus (HPV)-associated oropharyngeal cancer is rising. Thus, innovative therapy approaches are imperative in order to improve the situation. Everolimus, an inhibitor of the mammalian target of rapamycin (mTOR) and sorafenib and sunitinib, multityrosine kinase inhibitors, have been notably effective in the therapy of different tumor entities. The modest side-effects and oral application of the drugs might improve patient compliance. Expression levels of mTOR and Amphiregulin (AREG) in p16-positive and -negative SCC (squamous cell carcinoma) and the effect of everolimus, sorafenib or sunitinib on the expression levels of these target proteins were assessed. As far as we are aware of, this is one of the first in vitro studies to evaluate the effect of these small-molecule drugs with regard to the p16 status of SCC cells. p16-negative HNSCC 11A and 14C cells and p16-positive CERV196 cells were exposed to different concentrations of everolimus, sorafenib and sunitinib for 2-8 days. Expression levels of mTOR and AREG were determined by enzyme-linked immunosorbent assay (ELISA) and compared against a chemonaïve control. AREG and mTOR were expressed in all tested cell lines. CERV196 displayed a remarkable increase of mTOR expression compared to p16-negative HNSCC. On the contrary, AREG levels were reduced by 50% in CERV196. Everolimus, sorafenib and sunitinib significantly reduced mTOR expression. Everolimus significantly decreased AREG expression independently of the HPV status. Sunitinib and sorafenib increased AREG expression in HNSCC 11A and 14C but not in CERV196. The applied drugs showed remarkable suppression of mTOR expression, which might delay tumor progression. Interestingly, sorafenib and sunitinib increased AREG in HNSCC 11A and 14C, which could be a possible evasive mechanism following incubation with these drugs. On the contrary, p16-positive CERV196 showed increased susceptibility to sorafenib and sunitinib concerning suppression of AREG expression. Further studies are required to evaluate the HPV-dependent differences of therapy response and the possible consequences for treatment options. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Tri-modal confocal margin screening for the presence of residual squamous cell carcinoma in Mohs surgical excisions

NASA Astrophysics Data System (ADS)

Bar, Anna; Snavely, Nicholas; Chen, Nathaniel; Jacques, Steven; Gareau, Daniel S.

2012-03-01

Screening cancer in excision margins may be done with confocal microscopy to save time and cost over the gold standard histopathology (H&E). However, diagnostic accuracy requires sufficient contrast. Reflectance mode enables detection of large (>500um) nodular tumors. Enhanced nuclear contrast with acridine orange fluorescence mode additionally enables detection of tiny (<50um) basal cell carcinomas. Here, we present a novel combination of three modes to detect squamous cell carcinoma (SCC). Accurate screening of SCC requires eosin fluorescence, reflectance and acridine orange fluorescence to enable contrast for cytoplasm, collagen and nuclei respectively. Combining these signals replicates H&E for rapid clinical translation.

Non-solar ultraviolet radiation and the risk of basal and squamous cell skin cancer.

PubMed Central

Bajdik, C. D.; Gallagher, R. P.; Astrakianakis, G.; Hill, G. B.; Fincham, S.; McLean, D. I.

1996-01-01

A case-control study of non-melanocytic skin cancer was conducted among men in the province of Alberta, Canada. Two hundred and twenty-six cases of basal cell carcinoma (BCC), 180 cases of squamous cell carcinoma (SCC) and 406 age-matched controls provided information concerning skin pigmentation, occupational history, recreational activity, exposure to sunlight and sources of non-solar ultraviolet radiation (NSUVR) and other potential risk factors. Our analyses show no evidence of elevated risk for BCC or SCC among subjects exposed to various types of NSUVR. This is in opposition to studies of melanoma that have shown elevated risks for exposure to fluorescent lighting, sunlamps and sunbeds. PMID:8664139

Squamous cell carcinoma of penis with bullous pemphigoid masquerading as lymphogranuloma venereum

PubMed Central

Venugopal, V.; Gnanaraj, Pushpa; Fernandes, S. D.; Narasimhan, Murali; Karthikeyan, Subashini; Rahul, Shwetha

2013-01-01

We report a case of a 60-year old unmarried male who presented with multiple ulcers and foul smelling discharge from the groin since 4 months and multiple tense bullae over the trunk of 1 month duration. Groove sign was present. Investigations for lymphogranuloma venereum (LGV) and other sexually transmitted diseases were negative. Histopathology from the ulcer in the groin and growth in the penis revealed squamous cell carcinoma (SCC). Skin biopsy of bulla was diagnostic of bullous pemphigoid (BP). We report a rare case of SCC masquerading as LGV with BP occurring as a paraneoplastic phenomenon. PMID:23919055

Indoleamine 2,3-dioxygenase 1 and overall survival of patients diagnosed with esophageal cancer

PubMed Central

Rosenberg, Ari J.; Wainwright, Derek A.; Rademaker, Alfred; Galvez, Carlos; Genet, Matthew; Zhai, Lijie; Lauing, Kristen L.; Mulcahy, Mary F.; Hayes, John P.; Odell, David D.; Horbinski, Craig; Komanduri, Srinadh; Tetreault, Marie-Pier; Kim, Kwang-Youn A.; Villaflor, Victoria M.

2018-01-01

Background Indoleamine 2,3-dioxygenase 1 (IDO1) is an enzyme with immunomodulatory properties that has emerged as a potential immunotherapeutic target in human cancer. However, the role, expression pattern, and relevance of IDO1 in esophageal cancer (EC) are poorly understood. Here, we utilize gene expression analysis of the cancer genome atlas (TCGA) and immunohistochemistry (IHC) to better understand the role and prognostic significance of IDO1 in EC. Results High IDO1 mRNA levels were associated with worse overall survival (OS) in both esophageal squamous cell carcinoma (SCC) (P = 0.02) and adenocarcinoma (AC) (P = 0.036). High co-expression of IDO1 and programmed death ligand 1 (PD-L1) was associated with worse OS in SCC (P = 0.0031) and AC (P = 0.0186). IHC for IDO1 in SCC showed a significant correlation with PD-L1 (P < 0.0001) and CD3ε (P < 0.0001). Conclusions EC with high IDO1 and PD-L1 expression is significantly correlated with decreased patient survival, and may correlate with increased T-cells. These data suggest that simultaneous inhibition of IDO1 and PD-(L)1 may overcome important barriers to T-cell mediated immune rejection of EC. Materials and Methods mRNA expression data from TCGA (SCC N = 87; AC N = 97). IHC in a second cohort of EC (N = 93) were stained for IDO1, PD-L1, and CD3ε, followed by light microscopic analysis. PMID:29805749

Prothymosin-α and parathymosin expression predicts poor prognosis in squamous and adenosquamous carcinomas of the gallbladder

PubMed Central

Chen, Kang; Xiong, Li; Yang, Zhuling; Huang, Shengfu; Zeng, Rong; Miao, Xiongying

2018-01-01

The present study aimed to investigate the expression patterns of prothymosin-α (PTMA) and parathymosin (PTMS) in patients with squamous cell carcinoma (SCC), adenosquamous cell carcinoma (ASC) and adenocarcinoma (AC) of the gallbladder, and to assess their association with the clinicopathological characteristics and prognosis of the patients. A retrospective analysis of data pertaining to patients with SCC/ASC (n=46) and AC (n=80) of the gallbladder, who were treated with surgical resection, was conducted. Kaplan-Meier survival analysis was also performed to assess the correlation of the expression pattern with survival. The results revealed a higher percentage of patients with a large tumor diameter (>3 cm) in the SCC/ASC group as compared with those in the AC group (P<0.05). No significant differences were observed between patients with SCC/ASC and those with AC with respect to the patient sex, presence of gallstones, TNM stage, lymph node metastasis, invasive growth into anatomically contiguous structures, surgical methods used, survival rate, and the expression levels of PTMA and PTMA (P>0.05). However, positive expression of PTMA and PTMA was associated with tumor size, TNM stage, lymph node metastasis, locally invasive growth, and treatment with radical resection in patients with SCC/ASC and AC (P<0.05). In addition, positive expression of PTMA and PTMA was observed in a significantly lower number of patients with advanced AC as compared with those in early AC (P<0.05), while these expression levels were also associated with shorter survival in the SCC/ASC group and AC group (P<0.05). Cox multivariate analysis also demonstrated a negative correlation between PTMA and PTMA levels, and the postoperative survival rate in the two groups. In conclusion, the present study indicated that the expression levels of PTMA and PTMA were closely associated with the tumorigenesis and progression of SCC, ASC and AC of the gallbladder. Positive expression of PTMA and PTMA may serve as a valuable prognostic factor in these patients. PMID:29541218

Burden of invasive squamous cell carcinoma of the penis in the United States, 1998-2003.

PubMed

Hernandez, Brenda Y; Barnholtz-Sloan, Jill; German, Robert R; Giuliano, Anna; Goodman, Marc T; King, Jessica B; Negoita, Serban; Villalon-Gomez, Jose M

2008-11-15

Invasive squamous cell carcinoma (SCC) of the penis is rare in the United States. Although human papillomavirus (HPV) infection is an established etiologic agent in at least 40% of penile SCCs, relatively little is known about the epidemiology of this malignancy. Population-based data from the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) program, the Centers for Disease Control and Prevention's National Program for Cancer Registries, and the National Center for Health Statistics were used to examine invasive penile SCC incidence and mortality in the United States. SEER data were used to examine treatment of penile SCC. From 1998 to 2003, 4967 men were diagnosed with histologically confirmed invasive penile SCC in the United States, representing less than 1% of new cancers in men. The annual, average age-adjusted incidence rate was 0.81 cases per 100,000 men, and rates increased steadily with age. Overall, penile SCC incidence was comparable in whites and blacks, but approximately 2-fold lower in Asians/Pacific Islanders. Rates among Hispanics were 72% higher compared with non-Hispanics. Blacks compared with whites and Asians/Pacific Islanders and Hispanics compared with non-Hispanics were diagnosed at significantly younger ages. Higher rates of mortality were also observed among blacks compared with whites and Hispanics compared with non-Hispanics. Penile SCC incidence and mortality were elevated in Southern states and in regions of low socioeconomic status (SES). Some histologic and anatomic site differences were observed by race and ethnicity. Treatment of penile SCC varied with age, stage, and other tumor characteristics. There are considerable disparities in invasive penile cancer incidence and mortality in the United States. Key risk factors for excess incidence include Hispanic ethnicity and residence in the South and in low SES regions. Risks for excess mortality include these factors in addition to black race. Decreases in penile cancer incidence and mortality in the United States may be realized in the future as the indirect result of prophylactic HPV vaccination of females. Further research is needed to better understand the epidemiology of penile cancer including the role of HPV.

Evaluation of cannabinoid CB1 and CB2 receptors expression in mobile tongue squamous cell carcinoma: associations with clinicopathological parameters and patients' survival.

PubMed

Theocharis, Stamatios; Giaginis, Constantinos; Alexandrou, Paraskevi; Rodriguez, Jose; Tasoulas, Jason; Danas, Eugene; Patsouris, Efstratios; Klijanienko, Jerzy

2016-03-01

Cannabinoid receptors (CB1R and CB2R) constitute essential members of the endocannabinoid system (ECS) which participates in many different functions indispensable to homeostatic regulation in several tissues, exerting also antitumorigenic effects. The present study aimed to assess the clinical significance of CB1R and CB2R protein expression in mobile tongue squamous cell carcinoma (SCC). CB1R and CB2R expression was assessed immunohistochemically on 28 mobile tongue SCC tissue samples and was analyzed in relation with clinicopathological characteristics and overall and disease-free patients' survival. CB1R, CB2R, and concomitant CB1R/CB2R expression was significantly increased in older compared to younger mobile tongue SCC patients (p = 0.0243, p = 0.0079, and p = 0.0366, respectively). Enhanced CB2R and concomitant CB1R/CB2R expression was significantly more frequently observed in female compared to male mobile tongue SCC patients (p = 0.0025 and p = 0.0016, respectively). Elevated CB2R expression was significantly more frequently observed in mobile tongue SCC patients presenting well-defined tumor shape compared to those with diffuse (p = 0.0430). Mobile tongue SCC patients presenting enhanced CB1R, CB2R, or concomitant CB1R/CB2R expression showed significantly longer overall (log-rank test, p = 0.004, p = 0.011, p = 0.018, respectively) and disease-free (log-rank test, p = 0.003, p = 0.007, p = 0.027, respectively) survival times compared to those with low expression. In multivariate analysis, CB1R was identified as an independent prognostic factor for disease-free patients' survival (Cox-regression analysis, p = 0.032). The present study provides evidence that CB1R and CB2R may play a role in the pathophysiological aspects of the mobile tongue SCC and even each molecule may constitute a potential target for the development of novel anti-cancer drugs for this type of malignancy.

Burden of Invasive Squamous Cell Carcinoma of the Penis in the United States, 1998–2003

PubMed Central

Hernandez, Brenda Y.; Barnholtz-Sloan, Jill; German, Robert R.; Giuliano, Anna; Goodman, Marc T.; King, Jessica B.; Negoita, Serban; Villalon-Gomez, Jose M.

2009-01-01

BACKGROUND Invasive squamous cell carcinoma (SCC) of the penis is rare in the United States. Although human papillomavirus (HPV) infection is an established etiologic agent in at least 40% of penile SCCs, relatively little is known about the epidemiology of this malignancy. METHODS Population-based data from the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) program, the Centers for Disease Control and Prevention's National Program for Cancer Registries, and the National Center for Health Statistics were used to examine invasive penile SCC incidence and mortality in the United States. SEER data were used to examine treatment of penile SCC. RESULTS From 1998 to 2003, 4967 men were diagnosed with histologically confirmed invasive penile SCC in the United States, representing less than 1% of new cancers in men. The annual, average age-adjusted incidence rate was 0.81 cases per 100,000 men, and rates increased steadily with age. Overall, penile SCC incidence was comparable in whites and blacks, but approximately 2-fold lower in Asians/Pacific Islanders. Rates among Hispanics were 72% higher compared with non-Hispanics. Blacks compared with whites and Asians/Pacific Islanders and Hispanics compared with non-Hispanics were diagnosed at significantly younger ages. Higher rates of mortality were also observed among blacks compared with whites and Hispanics compared with non-Hispanics. Penile SCC incidence and mortality were elevated in Southern states and in regions of low socioeconomic status (SES). Some histologic and anatomic site differences were observed by race and ethnicity. Treatment of penile SCC varied with age, stage, and other tumor characteristics. CONCLUSIONS There are considerable disparities in invasive penile cancer incidence and mortality in the United States. Key risk factors for excess incidence include Hispanic ethnicity and residence in the South and in low SES regions. Risks for excess mortality include these factors in addition to black race. Decreases in penile cancer incidence and mortality in the United States may be realized in the future as the indirect result of prophylactic HPV vaccination of females. Further research is needed to better understand the epidemiology of penile cancer including the role of HPV. PMID:18980292

The multicentre south European study 'Helios'. II: Different sun exposure patterns in the aetiology of basal cell and squamous cell carcinomas of the skin.

PubMed Central

Rosso, S.; Zanetti, R.; Martinez, C.; Tormo, M. J.; Schraub, S.; Sancho-Garnier, H.; Franceschi, S.; Gafà, L.; Perea, E.; Navarro, C.; Laurent, R.; Schrameck, C.; Talamini, R.; Tumino, R.; Wechsler, J.

1996-01-01

The role of sun exposure in development of basal cell and squamous cell carcinomas among different populations from south Europe was investigated. Between 1989 and 1993 we interviewed incident cases and a random population sample of controls from five centres where a cancer registry was operating, whereas we selected a sample of hospital-based cases and controls from the other three centres. We gathered information on life-long exposure to sunlight during different activities. Results are analysed for 1549 basal cell carcinoma (BCC) cases and 228 squamous cell carcinoma (SCC) cases compared with 1795 controls. We observed a statistically significant increase of risk of SCC with increasing sun exposure beyond a threshold of 70,000 cumulated hours of exposure in a lifetime. Sun exposures during work and holidays were, however, inversely correlated. Odds ratios (ORs) of SCC were up to eight or nine times the reference for the highest exposures (200,000 cumulated hours or more). BCC exhibited a 2-fold increase of risk for lower exposure (8000-10,000 cumulated hours in a lifetime) with a plateau and a slight decrease of risk for the highest exposures (100,000 cumulated hours or more). Outdoor work showed a significantly increased risk of SCC (OR 1.6 for more than 54,000 cumulated hours of exposure in a lifetime), whereas recreational activities such as sun exposure during holidays at the beach (OR 1.6 for more than 2600 cumulated hours of exposure in a lifetime) or during water sports (OR 1.6 for more than 2600 cumulated hours of exposure in a lifetime) were associated with an increased risk of BCC. Risk patterns were different in poor or good tanners with a significant risk trend for good tanners, whereas poor tanners were on a plateau of increased risk at any level of exposure. Solar radiation is associated with a risk of BCC even for relatively short periods of exposure such as during holidays and sports, whereas SCC develops later if exposure continues. The skin's ability to tan modulates the risk of BCC; subjects who tan poorly have a steady risk increase, whereas people who tan easily develop cancer only after prolonged exposures. PMID:8645596

Establishment and evaluation of a stable steroidogenic caprine luteal cell line.

PubMed

Li, Wei; Xu, Xingang; Huang, Yong; Li, Zhaocai; Yu, Gaoshui; Wang, Zhisheng; Ding, Li; Tong, Dewen

2012-07-15

Many physiological, biological, pharmacologic, and toxicologic events and compounds affect the function of Saanen dairy goat luteal cells, resulting in implantation failure or early embryonic loss. Although primary luteal cell cultures have been used, their finite lifespan precludes assessment of long-term effects. In the present study, primary caprine luteal cells (CLCs) were immortalized through transfection of a plasmid containing the human telomerase reverse transcriptase (hTERT) gene. The expression of hTERT and telomerase activity were evaluated in transduced CLCs (hTERT-CLCs). In this study, these cells steadily expressed hTERT gene and exhibited higher telomerase activity at Passages 30 and 50. The hTERT-CLCs at Passages 30 and 50 expressed genes encoding key proteins, enzymes and receptors inherent to normal luteal cells, e.g., steroidogenic acute regulatory protein (StAR), cytochrome P450 cholesterol side-chain cleavage enzyme (P450scc), 3β-hydroxysteroid dehydrogenase (3β-HSD), and LH-receptor (LH-R). In addition, immortalized caprine luteal cells produced detectable quantities of progesterone in response to 8-bromo-cAMP (8-Br-cAMP) or 22(R)-hydroxycholesterol (22R-HC) stimulation. Furthermore, this cell line appeared to proliferate more quickly than control cells, although no neoplastic transformation occurred either in vivo or in vitro. We concluded the immortalized CLCs by hTERT retained their original characteristics and may provide a useful model to study luteal cell functions. Copyright © 2012 Elsevier Inc. All rights reserved.

Identification of differentially expressed genes in human lung squamous cell carcinoma using suppression subtractive hybridization.

PubMed

Sun, Wenyue; Zhang, Kaitai; Zhang, Xinyu; Lei, Wendong; Xiao, Ting; Ma, Jinfang; Guo, Suping; Shao, Shujuan; Zhang, Husheng; Liu, Yan; Yuan, Jinsong; Hu, Zhi; Ma, Ying; Feng, Xiaoli; Hu, Songnian; Zhou, Jun; Cheng, Shujun; Gao, Yanning

2004-08-20

Lung cancer is one of the major causes of cancer-related deaths. Over the past decade, much has been known about the molecular changes associated with lung carcinogenesis; however, our understanding to lung tumorigenesis is still incomplete. To identify genes that are differentially expressed in squamous cell carcinoma (SCC) of the lung, we compared the expression profiles between primarily cultured SCC tumor cells and bronchial epithelial cells derived from morphologically normal bronchial epithelium of the same patient. Using suppression subtractive hybridization (SSH), two cDNA libraries containing up- and down-regulated genes in the tumor cells were constructed, named as LCTP and LCBP. The two libraries comprise 258 known genes and 133 unknown genes in total. The known up-regulated genes in the library LCTP represented a variety of functional groups; including metabolism-, cell adhesion and migration-, signal transduction-, and anti-apoptosis-related genes. Using semi-quantitative reverse transcription-polymerase chain reaction, seven genes chosen randomly from the LCTP were analyzed in the tumor tissue paired with its corresponding adjacent normal lung tissue derived from 16 cases of the SCC. Among them, the IQGAP1, RAP1GDS1, PAICS, MLF1, and MARK1 genes showed a consistent expression pattern with that of the SSH analysis. Identification and further characterization of these genes may allow a better understanding of lung carcinogenesis.