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Sample records for a431 carcinoma cells

  1. Anticancer effects of cantharidin in A431 human skin cancer (Epidermoid carcinoma) cells in vitro and in vivo.

    PubMed

    Li, Chi-Chuan; Yu, Fu-Shun; Fan, Ming-Jen; Chen, Ya-Yin; Lien, Jin-Cherng; Chou, Yu-Cheng; Lu, Hsu-Feng; Tang, Nou-Ying; Peng, Shu-Fen; Huang, Wen-Wen; Chung, Jing-Gung

    2017-03-01

    Cantharidin (CTD), a potential anticancer agent of Traditional Chinese Medicine has cytotxic effects in different human cancer cell lines. The cytotoxic effects of CTD on A431 human skin cancer (epidermoid carcinoma) cells in vitro and in A431 cell xenograft mouse model were examined. In vitro, A431 human skin cell were treated with CTD for 24 and 48 h. Cell phase distribution, ROS production, Ca 2+ release, Caspase activity and the level of apoptosis associated proteins were measured. In vivo, A431 cell xenograft mouse model were examined. CTD-induced cell morphological changes and decreased percentage of viable A431 cells via G0/G1 phase arrest and induced apoptosis. CTD-induced G0/G1 phase arrest through the reduction of protein levels of cyclin E, CDK6, and cyclin D in A431 cells. CTD-induced cell apoptosis of A431 cells also was confirm by DNA gel electrophoresis showed CTD-induced DNA fragmentation. CTD reduced the mitochondrial membrane potential and stimulated release of cytochrome c, AIF and Endo G in A431 cells. Flow cytometry demonstrated that CTD increased activity of caspase-8, -9 and -3. However, when cells were pretreated with specific caspase inhibitors activity was reduced and cell viability increased. CTD increased protein levels of death receptors such as DR4, DR5, TRAIL and levels of the active form of caspase-8, -9 and -3 in A431 cells. AIF and Endo G proteins levels were also enhanced by CTD. In vivo studies showed that CTD significantly inhibited A431 cell xenograft tumors in mice. Taken together, these in vitro and in vivo results provide insight into the mechanisms of CTD on cell growth and tumor production. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 723-738, 2017. © 2016 Wiley Periodicals, Inc.

  2. Identification of specific gravity sensitive signal transduction pathways in human A431 carcinoma cells

    NASA Astrophysics Data System (ADS)

    Rijken, P. J.; de Groot, R. P.; Kruijer, W.; de Laat, S. W.; Verkleij, A. J.; Boonstra, J.

    Epidermal growth factor (EGF) activates a well characterized signal transduction cascade in human A431 epidermoid carcinoma cells. The influence of gravity on EGF-induced EGF-receptor clustering and early gene expression as well as on actin polymerization and actin organization have been investigated. Different signalling pathways induced by the agents TPA, forskolin and A23187 that activate gene expression were tested for sensitivity to gravity. EGF-induced c-fos and c-jun expression were decreased in microgravity. However, constitutive β-2 microglobulin expression remained unaltered. Under simulated weightlessness conditions EGF- and TPA-induced c-fos expression was decreased, while forskolin- and A23187-induced c-fos expression was independent of the gravity conditions. These results suggest that gravity affects specific signalling pathways. Preliminary results indicate that EGF-induced EGF-receptor clustering remained unaltered irrespective of the gravity conditions. Furthermore, the relative filamentous actin content of steady state A431 cells was enhanced under microgravity conditions and actin filament organization was altered. Under simulated weightlessness actin filament organization in steady state cells as well as in EGF-treated cells was altered as compared to the 1 G reference experiment. Interestingly the microtubule and keratin organization in untreated cells showed no difference with the normal gravity samples. This indicates that gravity may affect specific components of the signal transduction circuitry.

  3. The growth of human fibroblasts and A431 epidermoid carcinoma cells on gamma-irradiated human amnion collagen substrata.

    PubMed

    Liu, B; Harrell, R; Lamb, D J; Dresden, M H; Spira, M

    1989-10-15

    Human fibroblasts and A431 human epidermoid carcinoma cells were cultured on gamma-irradiated human amnion collagen as well as on plastic dishes and non-irradiated collagen coated dishes. The morphology, attachment, growth and short-term cytotoxicity of these culture conditions have been determined. Both irradiated and non-irradiated amnion collagen enhanced the attachment and proliferation of fibroblasts as compared to the plastic dishes. No differences in these properties were observed for A431 cells cultured on irradiated collagen when compared with culture on non-irradiated collagen substrates. Cytotoxicity assays showed that irradiated and non-irradiated collagens were not cytotoxic for either fibroblasts or A431 cells. The results demonstrated that amnion collagen irradiated at doses of 0.25-2.0 Mrads is optimal for cell growth.

  4. Toxicity of dimethylmonothioarsinic acid toward human epidermoid carcinoma A431 cells.

    PubMed

    Naranmandura, Hua; Ibata, Kenji; Suzuki, Kazuo T

    2007-08-01

    Chronic ingestion of arsenic-contaminated drinking water induces skin lesions and urinary bladder cancer in humans. It is now recognized that thioarsenicals such as dimethylmonothioarsinic acid (DMMTA (V)) are commonly excreted in the urine of humans and animals and that the production of DMMTA (V) may be a risk factor for the development of the diseases caused by arsenic. The toxicity of DMMTA (V) was compared with that of related nonthiolated arsenicals with respect to cell viability, uptake ability, generation of reactive oxygen species (ROS), and cell cycle progression of human epidermoid carcinoma A431 cells, arsenate (iAs (V)), arsenite (iAs (III)), dimethylarsinic acid (DMA (V)), and dimethylarsinous acid (DMA (III)) being used as reference nonthiolated arsenicals. DMMTA (V) (LC 50 = 10.7 microM) was shown to be much more cytotoxic than iAs (V) (LC 50 = 571 microM) and DMA (V) (LC 50 = 843 microM), and its potency was shown to be close to that of trivalent arsenicals iAs (III) (LC 50 = 5.49 microM) and DMA (III) (LC 50 = 2.16 microM). The greater cytotoxicity of DMMTA (V) was associated with greater cellular uptake and distribution, and the level of intracellular ROS remarkably increased in A431 cells upon exposure to DMMTA (V) compared to that after exposure to other trivalent arsenicals at the respective LC 50. Exposure of DMMTA (V) to cells for 24 h induced cell cycle perturbation. Namely, the percentage of cells residing in S and G2/M phases increased from 10.2 and 15.6% to 46.5 and 20.8%, respectively. These results suggest that although DMMTA (V) is a pentavalent arsenical, it is taken up efficiently by cells and causes various levels of toxicity, in a manner different from that of nonthiolated pentavalent arsenicals, demonstrating that DMMTA (V) is one of the most toxic arsenic metabolites. The high cytotoxicity of DMMTA (V) was explained and/or proposed by (1) efficient uptake by cells followed by (2) its transformation to DMA (V), (3) producing ROS

  5. Purification of high-molecular-weight subfraction from porcine skin inhibiting proliferation of A431 human carcinoma epidermoid cells.

    PubMed

    Belova, O V; Sergienko, V I; Arion, V Ya; Lukanidina, T A; Moskvina, S N; Zimina, I V; Borisenko, G G; Lutsenko, G V; Grechikhina, M V; Kovaleva, E V; Klyuchnikova, Zh I

    2014-07-01

    Subfraction with a molecular weight >250 kDa isolated from porcine skin and inhibiting the proliferation of A431 human carcinoma epidermoid cells was purified by DEAE 32 anion exchange chromatography with NaCl concentration step-gradient. The effects of the initial subfraction and fractions obtained by separation in DEAE 32 on the proliferation of A431 human carcinoma epidermoid cells were studied in vitro in two tests (MTT and fluorescent test). The more sensitive fluorescent test showed the highest inhibitory activity of fraction No. 2 released from the column at 0.15 M NaCl. One major protein component and a series of minor protein components were detected in this fraction by vertical PAAG-SDS electrophoresis.

  6. Flurbiprofen benzyl nitrate (NBS-242) inhibits the growth of A-431 human epidermoid carcinoma cells and targets β-catenin.

    PubMed

    Nath, Niharika; Liu, Xiaoping; Jacobs, Lloydine; Kashfi, Khosrow

    2013-01-01

    The Wnt/β-catenin/T cell factor (TCF) signaling pathway is important in the development of nonmelanoma skin cancers (NMSCs). Nitric-oxide-releasing nonsteroidal anti-inflammatory drugs (NO-NSAIDs) are chemopreventive agents consisting of a traditional NSAID attached to an NO-releasing moiety through a chemical spacer. Previously we showed that an aromatic spacer enhanced the potency of a particular NO-NSAID compared to an aliphatic spacer. We synthesized an NO-releasing NSAID with an aromatic spacer (flurbiprofen benzyl nitrate, NBS-242), and using the human skin cancer cell line A-431, we evaluated its effects on cell kinetics, Wnt/β-catenin, cyclin D1, and caspase-3. NBS-242 inhibited the growth of A-431 cancer cells, being ~15-fold more potent than flurbiprofen and up to 5-fold more potent than NO-flurbiprofen with an aliphatic spacer, the half maximal inhibitory concentrations (IC50) for growth inhibition being 60 ± 4 μM, 320 ± 20 μM, and 880 ± 65 μM for NBS-242, NO-flurbiprofen, and flurbiprofen, respectively. This effect was associated with inhibition of proliferation, accumulation of cells in the G0/G1 phase of the cell cycle, and an increase in apoptotic cell population. NBS-242 cleaved β-catenin both in the cytoplasm and the nucleus of A-431 cells. NBS-242 activated caspase-3 whose activation was reflected in the cleavage of procaspase-3. To test the functional consequence of β-catenin cleavage, we determined the expression of cyclin D1, a Wnt-response gene. NBS-242 reduced cyclin D1 levels in a concentration dependent manner. These findings establish a strong inhibitory effect of NBS-242 in A-431 human epidermoid carcinoma cells. NBS-242 modulates parameters that are important in determining cellular mass.

  7. Regulation of apoptosis by resveratrol through JAK/STAT and mitochondria mediated pathway in human epidermoid carcinoma A431 cells

    SciTech Connect

    Madan, Esha; Prasad, Sahdeo; Roy, Preeti

    2008-12-26

    Resveratrol (trans-3,4',5-trihydroxystilbene), a polyphenolic phytoalexin present mainly in grapes, red wine and berries, is known to possess strong chemopreventive and anticancer properties. Here, we demonstrated the anti-proliferative and apoptosis-inducing activities of resveratrol in human epidermoid carcinoma A431 cells. Resveratrol has cytotoxic effects through inhibiting cellular proliferation of A431 cells, which leads to the induction of apoptosis, as evident by an increase in the fraction of cells in the sub-G{sub 1} phase of the cell cycle and Annexin-V binding of externalized phosphatidylserine. Results revealed that inhibition of proliferation is associated with regulation of the JAK/STAT pathway, where resveratrol prevents phosphorylation ofmore » JAK, thereby inhibiting STAT1 phosphorylation. Furthermore, resveratrol treatment actively stimulated reactive oxygen species (ROS) and mitochondrial membrane depolarization. Consequently, an imbalance in the Bax/Bcl-2 ratio triggered the caspase cascade and subsequent cleavage of PARP, thereby shifting the balance in favor of apoptosis. These observations indicate that resveratrol treatment inhibits JAK/STAT-mediated gene transcription and induce the mitochondrial cell death pathway.« less

  8. Resveratrol enhances ultraviolet B-induced cell death through nuclear factor-{kappa}B pathway in human epidermoid carcinoma A431 cells

    SciTech Connect

    Roy, Preeti; Kalra, Neetu; Nigam, Nidhi

    Resveratrol has been reported to suppress cancer progression in several in vivo and in vitro models, whereas ultraviolet B (UVB), a major risk for skin cancer, is known to induce cell death in cancerous cells. Here, we investigated whether resveratrol can sensitize A431 human epidermoid carcinoma cells to UVB-induced cell death. We examined the combined effect of UVB (30 mJ/cm{sup 2}) and resveratrol (60 {mu}M) on A431 cells. Exposure of A431 carcinoma cells to UVB radiation or resveratrol can inhibit cell proliferation and induce apoptosis. However, the combination of resveratrol and UVB exposure was associated with increased proliferation inhibition ofmore » A431 cells compared with either agent alone. Furthermore, results showed that resveratrol and UVB treatment of A431 cells disrupted the nuclear factor-kappaB (NF-{kappa}B) pathway by blocking phosphorylation of serine 536 and inactivating NF-{kappa}B and subsequent degradation of I{kappa}B{alpha}, which regulates the expression of survivin. Resveratrol and UVB treatment also decreased the phosphorylation of tyrosine 701 of the important transcription factor signal transducer activator of transcription (STAT1), which in turn inhibited translocation of phospho-STAT1 to the nucleus. Moreover, resveratrol/UVB also inhibited the metastatic protein LIMK1, which reduced the motility of A431 cells. In conclusion, our study demonstrates that the combination of resveratrol and UVB act synergistically against skin cancer cells. Thus, resveratrol is a potential chemotherapeutic agent against skin carcinogenesis.« less

  9. Fisetin inhibits growth, induces G2/M arrest and apoptosis of human epidermoid carcinoma A431 cells: Role of mitochondrial membrane potential disruption and consequent caspases activation

    PubMed Central

    Pal, Harish C.; Sharma, Samriti; Elmets, Craig A.; Athar, Mohammad; Afaq, Farrukh

    2013-01-01

    Non-melanoma skin cancers (NMSCs) one of the most common neoplasms causes serious morbidity and mortality. Therefore, identification of non-toxic phytochemicals for prevention/treatment of NMSCs is highly desirable. Fisetin (3,3′,4′,7-tetrahydroxyflavone), a dietary flavonoid, present in fruits and vegetables possesses anti-oxidant and anti-proliferative properties. The aim of this study was to investigate the chemotherapeutic potential of fisetin in cultured human epidermoid carcinoma A431 cells. Treatment of A431 cells with fistein (5-80 μM) resulted in a significant decrease in cell viability in a dose- and time-dependent manner. Employing clonogenic assay, we found that fisetin treatment significantly reduced colony formation in A431 cells. Fisetin treatment of A431 cells resulted in G2/M arrest and induction of apoptosis. Furthermore, treatment of A431 cells with fisetin resulted in (i) decreased expression of anti-apoptotic proteins (Bcl2, Bcl-xL and Mcl-1), (ii) increased expression of pro-apoptotic proteins (Bax, Bak and Bad), (iii) disruption of mitochondrial potential, (iv) release of cytchrome c and Smac/DIABLO from mitochondria, (v) activation of caspases, and (vi) cleavage of PARP protein. Pretreatment of A431 cells with the pan-caspase inhibitor (Z-VAD-FMK) blocked fisetin-induced cleavage of caspases and PARP. Taken together, these data provide evidence that fisetin possesses chemotherapeutic potential against human epidermoid carcinoma A431 cells. Overall, these results suggest that fisetin could be developed as a novel therapeutic agent for the management of NMSCs. PMID:23800058

  10. Icotinib, a potent and specific EGFR tyrosine kinase inhibitor, inhibits growth of squamous cell carcinoma cell line A431 through negatively regulating AKT signaling.

    PubMed

    Gao, Zhenzhen; Chen, Wei; Zhang, Xiaohua; Cai, Peifen; Fang, Xianying; Xu, Qiang; Sun, Yang; Gu, Yanhong

    2013-06-01

    Icotinib is a potent and specific epidermal growth factor receptor tyrosine kinase inhibitor. In this study, we reported that icotinib had the antitumor activity on human squamous cell carcinoma cell line A431 in vitro. Meanwhile, adhesion to fibronectin and expression of integrin α3 and β1 were significantly reduced in a dose-dependent manner after the treatment of icotinib. Moreover, icotinib induced cell cycle arrested and affected expression of various cell cycle related proteins in squamous cancer cell line A431, whereas it did not cause apoptosis. Furthermore, icotinib remarkably down-regulated phosphorylation of protein kinase B (AKT) though blocking the interaction between 3-phosphoinositide-dependent protein kinase-1 (PDK1) and AKT in A431 cells. Taken together, it is shown that the small molecular compound, icotinib, has an anti-squamous cell carcinoma activity in vitro and its antitumor mechanism is associated with the blockage of the interaction between PDK1 and AKT. These results provide a novel strategy for anti-squamous cell carcinoma therapy. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  11. Alpha-santalol, a chemopreventive agent against skin cancer, causes G2/M cell cycle arrest in both p53-mutated human epidermoid carcinoma A431 cells and p53 wild-type human melanoma UACC-62 cells

    PubMed Central

    2010-01-01

    Background α-Santalol, an active component of sandalwood oil, has shown chemopreventive effects on skin cancer in different murine models. However, effects of α-santalol on cell cycle have not been studied. Thus, the objective of this study was to investigate effects of α-santalol on cell cycle progression in both p53 mutated human epidermoid carcinoma A431 cells and p53 wild-type human melanoma UACC-62 cells to elucidate the mechanism(s) of action. Methods MTT assay was used to determine cell viability in A431 cells and UACC-62; fluorescence-activated cell sorting (FACS) analysis of propidium iodide staining was used for determining cell cycle distribution in A431 cells and UACC-62 cells; immunoblotting was used for determining the expression of various proteins and protein complexes involved in the cell cycle progression; siRNA were used to knockdown of p21 or p53 in A431 and UACC-62 cells and immunofluorescence microscopy was used to investigate microtubules in UACC-62 cells. Results α-Santalol at 50-100 μM decreased cell viability from 24 h treatment and α-santalol at 50 μM-75 μM induced G2/M phase cell cycle arrest from 6 h treatment in both A431 and UACC-62 cells. α-Santalol altered expressions of cell cycle proteins such as cyclin A, cyclin B1, Cdc2, Cdc25c, p-Cdc25c and Cdk2. All of these proteins are critical for G2/M transition. α-Santalol treatment up-regulated the expression of p21 and suppressed expressions of mutated p53 in A431 cells; whereas, α-santalol treatment increased expressions of wild-type p53 in UACC-62 cells. Knockdown of p21 in A431 cells, knockdown of p21 and p53 in UACC-62 cells did not affect cell cycle arrest caused by α-santalol. Furthermore, α-santalol caused depolymerization of microtubules similar to vinblastine in UACC-62 cells. Conclusions This study for the first time identifies effects of α-santalol in G2/M phase arrest and describes detailed mechanisms of G2/M phase arrest by this agent, which might be

  12. Interference of silibinin with IGF-1R signalling pathways protects human epidermoid carcinoma A431 cells from UVB-induced apoptosis

    SciTech Connect

    Liu, Weiwei; Otkur, Wuxiyar; Li, Lingzhi

    Highlights: ► Silibinin protects A431 cells from UVB irradiation-induced apoptosis. ► Up-regulation of the IGF-1R-JNK/ERK pathways by UVB induces cell apoptosis. ► Silibinin inhibits IGF-1R pathways to repress caspase-8-mediated apoptosis. -- Abstract: Ultraviolet B (UVB) from sunlight is a major cause of cutaneous lesion. Silibinin, a traditional hepatic protectant, elicits protective effects against UVB-induced cellular damage. In A431 cells, the insulin-like growth factor-1 receptor (IGF-1R) was markedly up-regulated by UVB irradiation. The activation of the IGF-1R signalling pathways contributed to apoptosis of the cells rather than rescuing the cells from death. Up-regulated IGF-1R stimulated downstream mitogen-activated protein kinases (MAPKs), suchmore » as c-Jun N-terminal kinases (JNK) and extracellular signal-regulated protein kinases 1/2 (ERK1/2). The subsequent activation of caspase-8 and caspase-3 led to apoptosis. The activation of IGF-1R signalling pathways is the cause of A431 cell death. The pharmacological inhibitors and the small interfering RNA (siRNA) targeting IGF-1R suppressed the downstream activation of JNK/ERK-caspases to help the survival of the UVB-irradiated A431 cells. Indeed, silibinin treatment suppressed the IGF-1R-JNK/ERK pathways and thus protected the cells from UVB-induced apoptosis.« less

  13. Induction of apoptosis by lupeol in human epidermoid carcinoma A431 cells through regulation of mitochondrial, Akt/PKB and NFkappaB signaling pathways.

    PubMed

    Prasad, Sahdeo; Madan, Esha; Nigam, Nidhi; Roy, Preeti; George, Jasmine; Shukla, Yogeshwer

    2009-09-01

    The rising incidence of skin cancer in humans makes it equivalent to malignancies of organs. Therefore, it is necessary to intensify our efforts for better understanding and development of novel treatment and preventive approaches for skin cancer. Fruits and other plant derived products have gained considerable attention as they can reduce the risk of several cancer types. Lupeol, a triterpene, present in many fruits and medicinal plants, has been shown to possess many pharmacological properties including anti-cancer effect in both in vitro and in vivo assay systems. In the present study, apoptosis inducing effects of lupeol were studied in human epidermoid carcinoma A431 cells. Cell cycle analysis showed that lupeol treatment induces apoptosis (14-37%) in a dose-dependent manner as evident by an increased sub G(1) cell population. The RT-PCR and Western blot analysis showed that lupeol-induced apoptosis was associated with caspase dependent mitochondrial cell death pathway through activation of Bax, caspases, Apaf1, decrease in Bcl-2 expression and subsequent cleavage of PARP. Lupeol treatment also inhibited Akt/PKB signaling pathway by inhibition of Bad (Ser136) phosphorylation and 14-3-3 expression. In addition, lupeol treatment inhibited cell survival by inactivation of NFkappaB through upregulation of its inhibitor Ikappabetaalpha. The Caspase mediated apoptosis was noticed by decrease in lupeol induced apoptosis by Caspase inhibitors as well as increase in reactive oxygen species generation and loss of mitochondrial membrane potential. These results suggest that lupeol could be an effective anti-cancer agent and merits further investigation.

  14. Bromelain inhibits nuclear factor kappa-B translocation, driving human epidermoid carcinoma A431 and melanoma A375 cells through G(2)/M arrest to apoptosis.

    PubMed

    Bhui, Kulpreet; Tyagi, Shilpa; Srivastava, Amit Kumar; Singh, Madhulika; Roy, Preeti; Singh, Richa; Shukla, Yogeshwer

    2012-03-01

    Bromelain, obtained from pineapple, is already in use clinically as adjunct in chemotherapy. Our objective was to test its ability to act as a sole anti-cancer agent. Therefore, we describe its anti-proliferative, anti-inflammatory and subsequent anti-cancer effects in vitro, against human epidermoid carcinoma-A431 and melanoma-A375 cells. Bromelain exhibited reduction in proliferation of both these cell-lines and suppressed their potential for anchorage-independent growth. Further, suppression of inflammatory signaling by bromelain was evident by inhibition of Akt regulated-nuclear factor-kappaB activation via suppression of inhibitory-kappaBα phosphorylation and concomitant reduction in cyclooxygenase-2. Since, the inflammatory cascade is well-known to be closely allied to cancer; we studied the effect of bromelain on events/molecules central to it. Bromelain caused depletion of intracellular glutathione and generation of reactive oxygen-species followed by mitochondrial membrane depolarization. This led to bromelain-induced cell-cycle arrest at G(2)/M phase which was mediated by modulation of cyclin B1, phospho-cdc25C, Plk1, phospho-cdc2, and myt1. This was subsequently followed by induction of apoptosis, indicated by membrane-blebbing, modulation of Bax-Bcl-2 ratio, Apaf-1, caspase-9, and caspase-3; chromatin-condensation, increase in caspase-activity and DNA-fragmentation. Bromelain afforded substantial anti-cancer potential in these settings; hence we suggest it as a potential prospect for anti-cancer agent besides only an additive in chemotherapy. Copyright ©2011 Wiley Periodicals, Inc.

  15. Diosmin reduces cell viability of A431 skin cancer cells through apoptotic induction.

    PubMed

    Buddhan, Rajamanickam; Manoharan, Shanmugam

    2017-01-01

    Aim of the present study was to evaluate the in vitro cytotoxic potential of the diosmin in A431 skin cancer cells. The cytotoxic (anti-cell proliferative) potential of diosmin in A431 cells was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay (cell viability), dual staining (apoptotic induction), dichloro-dihydro-fluorescein diacetate assay (reactive oxygen species [ROS] generation), DNA fragmentation study, Western blotting analysis (apoptotic markers expression) and flow cytometry (cell cycle arrest). Diosmin reduced the cell viability of A431 cells in a dose-dependent fashion and the inhibitory concentration 50% value was attained at 45 μg/ml using MTT assay. Diosmin at a concentration of 45 μg/ml generated excessive ROS in A431 cells, as compared to untreated cells. Diosmin treated A431 cells also revealed multiple DNA fragments than the untreated cells. Diosmin upregulated the expression of p53, caspases 3 and 9 and downregulated the expression of Bcl-2, matrix metalloproteinases-2 and 9 in A431 cells. The cytotoxic or anti-cell proliferative potential of diosmin is due to its ROS-mediated apoptotic induction potential, as well as due to its role in the inhibition of invasion in the A431 cells.

  16. A green approach toward quinoxalines and bis-quinoxalines and their biological evaluation against A431, human skin cancer cell lines.

    PubMed

    Bandyopadhyay, Debasish; Cruz, Jessica; Morales, Liza D; Arman, Hadi D; Cuate, Erica; Lee, Young S; Banik, Bimal K; Kim, Dae J

    2013-08-01

    The objective of this study was to develop a practical green procedure to synthesize quinoxalines and bis-quinoxalines and evaluate their inhibitory effects on the viability of A431 human epidermoid carcinoma cells. A series of quinoxaline and bis-quinoxaline derivatives have been designed and synthesized following a microwave-assisted and bismuth nitrate-catalyzed eco-friendly route. A detailed comparison has been made between microwave-induced protocol with the reactions occurred at room temperature. The structure of the compounds have been elucidated by various spectroscopic methods and finally confirmed by x-ray crystallographic analyses. Two quinoxaline derivatives, compounds 6 and 12 have demonstrated inhibitory effects on the viability of A431 human epidermoid carcinoma cells when compared with HaCaT nontumorigenic human keratinocyte cells. Notably, compound 6 inhibits Stat3 phosphorylation/activation in A431 skin cancer cells.

  17. Expression of heparanase in basal cell carcinoma and squamous cell carcinoma.

    PubMed

    Pinhal, Maria Aparecida Silva; Almeida, Maria Carolina Leal; Costa, Alessandra Scorse; Theodoro, Thérèse Rachell; Serrano, Rodrigo Lorenzetti; Machado, Carlos D'Apparecida Santos

    2016-01-01

    Heparanase is an enzyme that cleaves heparan sulfate chains. Oligosaccharides generated by heparanase induce tumor progression. Basal cell carcinoma and squamous cell carcinoma comprise types of nonmelanoma skin cancer. Evaluate the glycosaminoglycans profile and expression of heparanase in two human cell lines established in culture, immortalized skin keratinocyte (HaCaT) and squamous cell carcinoma (A431) and also investigate the expression of heparanase in basal cell carcinoma, squamous cell carcinoma and eyelid skin of individuals not affected by the disease (control). Glycosaminoglycans were quantified by electrophoresis and indirect ELISA method. The heparanase expression was analyzed by quantitative RT-PCR (qRTPCR). The A431 strain showed significant increase in the sulfated glycosaminoglycans, increased heparanase expression and decreased hyaluronic acid, comparing to the HaCaT lineage. The mRNA expression of heparanase was significantly higher in Basal cell carcinoma and squamous cell carcinoma compared with control skin samples. It was also observed increased heparanase expression in squamous cell carcinoma compared to the Basal cell carcinoma. The glycosaminoglycans profile, as well as heparanase expression are different between HaCaT and A431 cell lines. The increased expression of heparanase in Basal cell carcinoma and squamous cell carcinoma suggests that this enzyme could be a marker for the diagnosis of such types of non-melanoma cancers, and may be useful as a target molecule for future alternative treatment.

  18. Binding of fluoresceinated epidermal growth factor to A431 cell sub-populations studied using a model-independent analysis of flow cytometric fluorescence data.

    PubMed Central

    Chatelier, R C; Ashcroft, R G; Lloyd, C J; Nice, E C; Whitehead, R H; Sawyer, W H; Burgess, A W

    1986-01-01

    A method is developed for determining ligand-cell association parameters from a model-free analysis of data obtained with a flow cytometer. The method requires measurement of the average fluorescence per cell as a function of ligand and cell concentration. The analysis is applied to data obtained for the binding of fluoresceinated epidermal growth factor to a human epidermoid carcinoma cell line, A431. The results indicate that the growth factor binds to two classes of sites on A431 cells: 4 X 10(4) sites with a dissociation constant (KD) of less than or equal to 20 pM, and 1.5 X 10(6) sites with a KD of 3.7 nM. A derived plot of the average fluorescence per cell versus the average number of bound ligands per cell is used to construct binding isotherms for four sub-populations of A431 cells fractionated on the basis of low-angle light scatter. The four sub-populations bind the ligand with equal affinity but differ substantially in terms of the number of binding sites per cell. We also use this new analysis to critically evaluate the use of 'Fluorotrol' as a calibration standard in flow cytometry. PMID:3015587

  19. Establishment of A431 cell membrane chromatography-RPLC method for screening target components from Radix Caulophylli.

    PubMed

    Hou, Xiaofang; Wang, Sicen; Hou, Jingjing; He, Langchong

    2011-03-01

    We describe here an analytical method of A431 cell membrane chromatography (A431/CMC) (CMC, cell membrane chromatography) combined with RPLC for recognition, separation, and identification of target components from traditional Chinese medicines (TCMs) Radix Caulophylli. The A431 cells with high expressed epidermal growth factor receptor (EGFR) were used to prepare the stationary phase in the CMC model. Retention fractions on the A431-CMC model were collected using an automated fraction collection and injection module (FC/I). Each fraction was analyzed by RPLC under the optimized conditions. Gefitinib and erlotinib were used as standard compounds to investigate the suitability and reliability of the A431 cell membrane chromatography-RPLC method prior to screening target component from Radix Caulophylli total alkaloids. The results indicated that caulophine and taspine were the target component acting on the epidermal growth factor receptor. This method could be an efficient way in drug discovery using natural medicinal herbs as a source of novel compounds. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Lysosomal Signaling Enhances Mitochondria-Mediated Photodynamic Therapy in A431 Cancer Cells: Role of Iron

    PubMed Central

    Saggu, Shalini; Hung, Hsin-I; Quiogue, Geraldine; Lemasters, John J.; Nieminen, Anna-Liisa

    2015-01-01

    In photodynamic therapy (PDT), light activates a photosensitizer added to a tissue, resulting in singlet oxygen formation and cell death. The photosensitizer phthalocyanine 4 (Pc 4) localizes primarily to mitochondrial membranes in cancer cells, resulting in mitochondria-mediated cell death. The aim of this study was to determine how lysosomes contribute to PDT-induced cell killing by mitochondria-targeted photosensitizers such as Pc 4. We monitored cell killing of A431 cells after Pc 4-PDT in the presence and absence of bafilomycin, an inhibitor of the vacuolar proton pump of lysosomes and endosomes. Bafilomycin was not toxic by itself, but greatly enhanced Pc 4-PDT-induced cell killing. To investigate whether iron loading of lysosomes affects bafilomycin-induced killing, cells were incubated with ammonium ferric citrate (30 μm) for 30 h prior to PDT. Ammonium ferric citrate enhanced Pc 4 plus bafilomycin-induced cell killing without having toxicity by itself. Iron chelators (desferrioxamine and starch-desferrioxamine) and the inhibitor of the mitochondrial calcium (and ferrous iron) uniporter, Ru360, protected against Pc 4 plus bafilomycin toxicity. These results support the conclusion that chelatable iron stored in the lysosomes enhances the efficacy of bafilomycin-mediated PDT and that lysosomal disruption augments PDT with Pc 4. PMID:22220628

  1. Up-regulation of the tight-junction protein ZO-1 by substance P and IGF-1 in A431 cells.

    PubMed

    Ko, Ji-Ae; Murata, Shizuka; Nishida, Teruo

    2009-08-01

    The formation of a barrier by tight junctions is important in epithelia of various tissues. Substance P (SP) and insulin-like growth factor (IGF)-1 synergistically promote barrier function in the corneal epithelium. We have now examined the effects of SP and IGF-1 on expression of the tight-junction protein zonula occludens (ZO)-1 in A431 human epidermoid carcinoma cells. Reverse transcription-polymerase chain reaction (RT-PCR) and immunoblot analyses revealed that SP and IGF-1 increased the amounts of ZO-1 mRNA and protein in these cells in a concentration-dependent manner, with neither SP nor IGF-1 alone having such an effect. The SP- and IGF-1-induced up-regulation of ZO-1 was accompanied by phosphorylation of extracellular signal-regulated kinase (ERK), and both of these effects were blocked by PD98059, an inhibitor of ERK activation. SP and IGF-1 also increased the transepithelial electrical resistance (TER) (an indicator of barrier function) of an A431 cell monolayer in a manner sensitive to PD98059. Our results thus suggest that the synergistic induction of ZO-1 expression by SP and IGF-1 may promote barrier function in skin epithelial cells. (c) 2009 John Wiley & Sons, Ltd.

  2. Biologically synthesised silver nanoparticles from three diverse family of plant extracts and their anticancer activity against epidermoid A431 carcinoma.

    PubMed

    Nayak, Debasis; Pradhan, Sonali; Ashe, Sarbani; Rauta, Pradipta Ranjan; Nayak, Bismita

    2015-11-01

    Biological synthesis of silver nanoparticles is a cost effective natural process where the phytochemicals specifically phenols, flavonoids and terpenoids present in the plant extracts act as capping and reducing agent. Due to their nano size regime the silver nanoparticles may directly bind to the DNA of the pathogenic bacterial strains leading to higher antimicrobial activity. In the current study silver nanoparticles were synthesised using plant extracts from different origin Cucurbita maxima (petals), Moringa oleifera (leaves) and Acorus calamus (rhizome). The synthesised nanoparticles were characterized by UV-visible spectroscopy, dynamic light scattering (DLS), X-ray diffraction (XRD), field emission scanning electron microscopy (Fe-SEM) and Fourier transform infrared spectroscopy (FTIR). Highly crystalline, roughly spherical and cuboidal silver nanoparticles of 30-70 nm in size were synthesised. The nanoparticles provided strong antimicrobial activity against pathogenic strains. The effect of the synthesised nanoparticles against A431 skin cancer cell line was tested for their toxicity by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) dye. The IC50 values of 82.39±3.1, 83.57±3.9 and 78.58±2.7 μg/ml were calculated for silver nanoparticles synthesised by C. maxima, M. oleifera and A. calamus respectively. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Proteolytic cleavage and activation of PAK2 during UV irradiation-induced apoptosis in A431 cells.

    PubMed

    Tang, T K; Chang, W C; Chan, W H; Yang, S D; Ni, M H; Yu, J S

    1998-09-15

    Exposure of mammalian cells to ultraviolet (UV) light elicits a cellular response and can also lead to apoptotic cell death. In this report, we show that a 36-kDa myelin basic protein (MBP) kinase detected by an in-gel kinase assay can be dramatically activated during the early stages of UV irradiation-triggered apoptosis of A431 cells. Immunoblot analysis revealed that this 36-kDa MBP kinase could be recognized by an antibody against the C-terminal regions of a family of p21Cdc42/Rac-activated kinases (PAKs). By using this antibody and a PAK2-specific antibody against the N-terminal region of PAK2 as studying tools, we further demonstrated that UV irradiation caused cleavage of PAK2 to generate a 36-kDa C-terminal catalytic fragment and a 30-kDa N-terminal fragment in A431 cells. The appearance of the 36-kDa C-terminal catalytic fragment of PAK2 matched exactly with the activation of the 36-kDa MBP kinase in A431 cells upon UV irradiation. In addition, UV irradiation also led to activation of CPP32/caspase-3, but not ICH-1L/caspase-2 and ICE/caspase-1, in A431 cells and the kinetics of activation of CPP32/caspase-3 appeared to correlate well with that of DNA fragmentation and of cleavage/activation of PAK2, respectively. Moreover, blockage of activation of CPP32/caspase-3 by pretreating the cells with two specific tetrapeptidic inhibitors for caspases (Ac-DEVD-cho and Ac-YVAD-cmk) could significantly attenuate the extent of cleavage/activation of PAK2 induced by UV irradiation. Collectively, the results demonstrate that cleavage and activation of PAK2 can be induced during the early stages of UV irradiation-triggered apoptosis and indicate the involvement of CPP32/caspase-3 in this process.

  4. CELL CARCINOMA].

    PubMed

    Drvar, D Ledić; Lipozenčić, J; Mokos, Z Bukvić; Ilić, I; Knežević, F

    2015-01-01

    An increase in the incidence of cancer, in particular skin cancer, has been observed in the last few decades. Skin cancer represents a significant public health problem in Croatia and worldwide. Cutaneous squamous cell carcinoma (cSCC) is a malignant tumor arising in epidermal keratinocytes. Together with basal cell carcinoma it belongs to non-melanoma skin cancers, which are the most common cancers in humans. The lifetime risk of cSCC development in Caucasian population is nowadays estimated to about 15%, which makes it double compared to 20 years ago. The most probable causes are increased ultraviolet light (UV) exposure (exposure to artificial UV sources in suntan parlors, spending more time outdoors, changes in fashion, as well as ozone holes), and longer life expectancy. In its etiopathogenesis, important risk factors include genetic factors, fair-skin phototype, UV exposure, chronic degenerative and inflammatory conditions, chemical factors, oncogenic viruses, immunosuppression, ionizing radiation, as well as habitual risk factors. Human epidermal growth factor receptor (HER) family is involved in the control of multiple signal pathways. Their dysregulation is associated with development of many cancers such as breast carcinoma, non-small cell lung carcinoma, ovarian carcinoma, carcinoma of pancreas, head and neck carcinoma, as well as glioblastoma. The objective of our investigation was to establish if there is association of the skin phototype and UV exposure with the expression of HER receptors, Ki67 and p53 in patients with cSCC. Study group included 101 cSCC patients. Inclusion criteria were age >50, both sexes, histopathologically confirmed cSCC, no previous therapy, specimens sufficient for immunohistochemistry, and complete clinical data collected by a questionnaire. Material obtained by excisional biopsy was completely histopathologically evaluated and additional tissue slices were immunohistochemically analyzed. Statistical analysis of the sample

  5. Oral Rigosertib for Squamous Cell Carcinoma

    ClinicalTrials.gov

    2017-06-22

    Head and Neck Squamous Cell Carcinoma; Anal Squamous Cell Carcinoma; Lung Squamous Cell Carcinoma; Cervical Squamous Cell Carcinoma; Esophageal Squamous Cell Carcinoma; Skin Squamous Cell Carcinoma; Penile Squamous Cell Carcinoma

  6. 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.

  7. Ebselen reduces the toxicity of mechlorethamine in A-431 cells via inhibition of apoptosis.

    PubMed

    Lulla, Anju; Pino, Maria A; Piętka-Ottlik, Magdalena; Młochowski, Jacek; Sparavalo, Oleksiy; Billack, Blase

    2013-06-01

    A series of test compounds were evaluated for an ability to reduce the toxicity of the nitrogen mustard mechlorethamine (HN2) in vitro. The test compounds included resveratrol, pterostilbene, vitamin C, ebselen, ebselen diselenide, and ebselen-sulfur. Among them, ebselen demonstrated the highest degree of protection against HN2 toxicity. To this end, pretreatment of the cells with ebselen offered protection against the toxicant whereas no protection was observed when cells were first incubated with HN2 and then treated with ebselen. Significant increases in caspase 3 and caspase 9 activities were observed in response to HN2, and ebselen was found to reduce these effects. Taken together, the data presented here indicate that ebselen is an effective countermeasure to nitrogen mustard in vitro, which is worthy of future investigation in vivo. © 2013 Wiley Periodicals, Inc.

  8. 1,4-Naphthoquinone activates the HSP90/HSF1 pathway through the S-arylation of HSP90 in A431 cells: Negative regulation of the redox signal transduction pathway by persulfides/polysulfides.

    PubMed

    Abiko, Yumi; Sha, Liang; Shinkai, Yasuhiro; Unoki, Takamitsu; Luong, Nho Cong; Tsuchiya, Yukihiro; Watanabe, Yasuo; Hirose, Reiko; Akaike, Takaaki; Kumagai, Yoshito

    2017-03-01

    The current consensus is that environmental electrophiles activate redox signal transduction pathways through covalent modification of sensor proteins with reactive thiol groups at low concentrations, while they cause cell damage at higher concentrations. We previously exposed human carcinoma A431 cells to the atmospheric electrophile 1,4-naphthoquinone (1,4-NQ) and found that heat shock protein 90 (HSP90), a negative regulator of heat shock factor 1 (HSF1), was a target of 1,4-NQ. In the study presented here, we determined whether 1,4-NQ activates HSF1. We also examined whether such redox signaling could be regulated by nucleophilic sulfur species. Exposure of A431 cells to 1,4-NQ covalently modified cellular HSP90, resulting in repression of the association between HSF1 with HSP90, thereby enhancing HSF1 translocation into the nuclei. Liquid chromatography-tandem mass spectrometry analysis with recombinant HSP90 revealed that the modifications site were Cys412 and Cys564. We found that HSF1 activation mediated by 1,4-NQ upregulated downstream genes, such as HSPA6. HSF1 knockdown accelerated 1,4-NQ-mediated cytotoxicity in the cells. While simultaneous treatment with reactive persulfide and polysulfide, Na 2 S 2 and Na 2 S 4 , blocked 1,4-NQ-dependent protein modification and HSF1 activation in A431 cells, the knockdown of Cys persulfide producing enzymes cystathionine β-synthase (CBS) and/or cystathionine γ-lyase (CSE) enhanced these phenomena. 1,4-NQ-thiol adduct and 1,4-NQ-S-1,4-NQ adduct were produced during the enzymatic reaction of recombinant CSE in the presence of 1,4-NQ. The results suggest that activation of the HSP90-HSF1 signal transduction pathway mediated by 1,4-NQ protects cells against 1,4-NQ and that per/polysulfides can diminish the reactivity of 1,4-NQ by forming sulfur adducts. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Inhibition of STAT-3 Results in Radiosensitization of Human Squamous Cell Carcinoma

    PubMed Central

    Bonner, James A.; Trummell, Hoa Q.; Willey, Christopher D.; Plants, Brian A.; Raisch, Kevin P.

    2009-01-01

    Background Signal Transducer and Activator of Transcription – 3 (STAT-3) is a downstream component of the Epidermal Growth Factor Receptor (EGFr) signaling process that may facilitate the resistance of tumor cells to conventional cancer treatments. Studies were performed to determine if inhibition of this downstream protein may produce radiosensitization. Methods/Results A431 cells (human squamous cell carcinoma cells with EGFr overexpression) were found to be sensitized to radiation after treatment with STAT-3 small interfering RNA (siRNA). Therefore, a short hairpin RNA (shRNA) against STAT-3 was designed and cloned into a pBABE vector system modified for shRNA expression. Following transfection, clone 2.1 was selected for further study as it showed a dramatic reduction of STAT-3 protein (and mRNA) when compared to A431 parental cells or a negative control shRNA cell line (transfected with STAT-3 shRNA with 2 base pairs mutated). A431 2.1 showed doubling times of 25-31 h as compared to 18-24 h for the parental cell line. The A431 shRNA knockdown STAT-3 cells A431 were more sensitive to radiation than A431 parental or negative STAT-3 control cells. Conclusion A431 cells stably transfected with shRNA against STAT-3 resulted in enhanced radiosensitivity. Further work will be necessary to determine whether inhibition of STAT-3 phosphorylation is a necessary step for the radiosensitization that is induced by inhibition of EGFr. PMID:19616333

  10. Nevoid basal cell carcinoma syndrome

    MedlinePlus

    NBCC syndrome; Gorlin-Goltz syndrome; Basal cell nevus syndrome; BCNS; Basal cell cancer - nevoid basal cell carcinoma syndrome ... Nevoid basal cell carcinoma nevus syndrome is a rare genetic condition. The gene linked to the syndrome is known as PTCH (" ...

  11. Basal Cell Carcinoma

    PubMed Central

    Lanoue, Julien

    2016-01-01

    Basal cell carcinoma is the most commonly occurring cancer in the world and overall incidence is still on the rise. While typically a slow-growing tumor for which metastases is rare, basal cell carcinoma can be locally destructive and disfiguring. Given the vast prevalence of this disease, there is a significant overall burden on patient well-being and quality of life. The current mainstay of basal cell carcinoma treatment involves surgical modalities, such as electrodessication and curettage, excision, cryosurgery, and Mohs micrographic surgery. Such methods are typically reserved for localized basal cell carcinoma and offer high five-year cure rates, but come with the risk of functional impairment, disfigurement, and scarring. Here, the authors review the evidence and indications for nonsurgical treatment modalities in cases where surgery is impractical, contraindicated, or simply not desired by the patient. PMID:27386043

  12. A combined A431 cell membrane chromatography and online high performance liquid chromatography/mass spectrometry method for screening compounds from total alkaloid of Radix Caulophylli acting on the human EGFR.

    PubMed

    Sun, Meng; Ren, Jing; Du, Hui; Zhang, Yanmin; Zhang, Jie; Wang, Sicen; He, Langchong

    2010-10-15

    We have developed an online analytical method that combines A431 cell membrane chromatography (A431/CMC) with high performance liquid chromatography and mass spectrometry (LC/MS) for identifying active components from Radix Caulophylli acting on human EGFR. Retention fractions on A431/CMC model were captured onto an enrichment column and the components were directly analyzed by combining a 10-port column switcher with an LC/MS system for separation and preliminary identification. Using Sorafenib tosylate as a positive control, taspine and caulophine from Radix Caulophylli were identified as the active molecules which could act on the EGFR. This A431/CMC-online-LC/MS method can be applied for screening active components acting on EGFR from traditional Chinese medicines exemplified by Radix Caulophylli and will be of great utility in drug discovery using natural medicinal herbs as a source of novel compounds. Copyright © 2010 Elsevier B.V. All rights reserved.

  13. [Sarcomatoid renal cell carcinoma].

    PubMed

    Arnoux, V; Lechevallier, E; Pamela, A; Long, J-A; Rambeaud, J-J

    2013-06-01

    The objective was to perform a systematic review of literature concerning epidemiology, clinical and biological data, prognosis and therapy of sarcomatoid renal cell carcinomas. Data on sarcomatoid renal cell carcinomas have been sought by querying the server Medline with MeSH terms following or combination of them: "renal carcinoma", "renal cell carcinoma," "renal cancer", "sarcomatoid" "sarcomatoid transformation" and "sarcomatoid differentiation." The articles obtained were selected according to their methodology, the language in English or French, the relevance and the date of publication. Twenty papers were selected. According to the literature, a sarcomatoid contingent can be observed in all subtypes of renal cell carcinomas, with a frequency of 1 to 15% of cases. The median age at diagnosis was 60 years with a majority of symptomatic patients (90%), mainly with abdominal pain and hematuria. These tumors were often found in patients with locally advanced or metastatic (45-77%). The imaging was not specific for the diagnosis and biopsy had a low sensitivity for identifying a sarcomatoid contingent. The treatment was based on a combination of maximal surgical resection whenever possible and systemic therapy for metastastic disease. Pathological data often showed large tumors, Furhman 4 grades, combined biphasic carcinomatous contingent (clear cell carcinoma in most cases) and sarcomatoid. Genetically, there was no specific abnormality but a complex association of chromosomal additions and deletions. The prognosis was pejorative with a specific median survival of 5 to 19 months without any impact of the sarcomatoid contingent rate. Sarcomatoid renal cell carcinoma is a form not to ignore despite its rarity. Mainly symptomatic and discovered at an advanced stage, it has a poor prognosis, requiring multidisciplinary management quickly and correctly. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  14. Stages of Merkel Cell Carcinoma

    MedlinePlus

    ... of Skin Cancer Skin Cancer Screening Research Merkel Cell Carcinoma Treatment (PDQ®)–Patient Version General Information About Merkel Cell Carcinoma Go to Health Professional Version Key Points ...

  15. Merkel Cell Carcinoma.

    PubMed

    Pulitzer, Melissa

    2017-06-01

    Merkel cell carcinoma (MCC) encompasses neuroendocrine carcinomas primary to skin and occurs most commonly in association with clonally integrated Merkel cell polyomavirus with related retinoblastoma protein sequestration or in association with UV radiation-induced alterations involving the TP53 gene and mutations, heterozygous deletion, and hypermethylation of the Retinoblastoma gene. Molecular genetic signatures may provide therapeutic guidance. Morphologic features, although patterned, are associated with predictable diagnostic pitfalls, usually resolvable by immunohistochemistry. Therapeutic options for MCC, traditionally limited to surgical intervention and later chemotherapy and radiation, are growing, given promising early results of immunotherapeutic regimens. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Extracellular ATP is a mitogen for 3T3, 3T6, and A431 cells and acts synergistically with other growth factors.

    PubMed Central

    Huang, N; Wang, D J; Heppel, L A

    1989-01-01

    Extracellular ATP in concentrations of 5-50 microM displayed very little mitogenic activity by itself but it caused synergistic stimulation of [3H]thymidine incorporation in the presence of phorbol 12-tetradecanoate 13-acetate, epidermal growth factor, platelet-derived growth factor, insulin, adenosine, or 5'-(N-ethyl)carboxamidoadenosine. Cultures of Swiss 3T3, Swiss 3T6, A431, DDT1-MF2, and HFF cells were used. The percent of cell nuclei labeled with [3H]thymidine and cell number were also increased. ADP was equally mitogenic, while UTP and ITP were much less active. The effect of ATP was not due to hydrolysis by ectoenzymes to form adenosine, a known growth factor. Thus, the nonhydrolyzable analogue adenosine 5'-[beta, gamma-imido]triphosphate was mitogenic. In addition, it was found that ATP showed synergism in 3T6 and 3T3 cells when present for only the first hour of an incorporation assay, during which time no significant hydrolysis occurred. Furthermore, prolonged preincubation of cells with ATP reduced the mitogenic response to ATP but not to adenosine; preincubation with adenosine or N6-(R-phenylisopropyl)adenosine had the reverse effect. Finally, the effect of adenosine, but not of ATP, was inhibited by aminophylline. We conclude that extracellular ATP is a mitogen that interacts with P2 purinoceptors on the plasma membrane. PMID:2813367

  17. Induction of Apoptosis and Antiproliferative Activity of Naringenin in Human Epidermoid Carcinoma Cell through ROS Generation and Cell Cycle Arrest

    PubMed Central

    Jafri, Asif; Ahmad, Sheeba; Afzal, Mohammad; Arshad, Md

    2014-01-01

    A natural predominant flavanone naringenin, especially abundant in citrus fruits, has a wide range of pharmacological activities. The search for antiproliferative agents that reduce skin carcinoma is a task of great importance. The objective of this study was to analyze the anti-proliferative and apoptotic mechanism of naringenin using MTT assay, DNA fragmentation, nuclear condensation, change in mitochondrial membrane potential, cell cycle kinetics and caspase-3 as biomarkers and to investigate the ability to induce reactive oxygen species (ROS) initiating apoptotic cascade in human epidermoid carcinoma A431 cells. Results showed that naringenin exposure significantly reduced the cell viability of A431 cells (p<0.01) with a concomitant increase in nuclear condensation and DNA fragmentation in a dose dependent manner. The intracellular ROS generation assay showed statistically significant (p<0.001) dose-related increment in ROS production for naringenin. It also caused naringenin-mediated epidermoid carcinoma apoptosis by inducing mitochondrial depolarization. Cell cycle study showed that naringenin induced cell cycle arrest in G0/G1 phase of cell cycle and caspase-3 analysis revealed a dose dependent increment in caspase-3 activity which led to cell apoptosis. This study confirms the efficacy of naringenin that lead to cell death in epidermoid carcinoma cells via inducing ROS generation, mitochondrial depolarization, nuclear condensation, DNA fragmentation, cell cycle arrest in G0/G1 phase and caspase-3 activation. PMID:25330158

  18. Inhibition of Phosphatidylcholine-Specific Phospholipase C Interferes with Proliferation and Survival of Tumor Initiating Cells in Squamous Cell Carcinoma

    PubMed Central

    Ferri, Renata; Mercurio, Laura; Canevari, Silvana; Podo, Franca; Miotti, Silvia; Iorio, Egidio

    2015-01-01

    Purpose The role of phosphatidylcholine-specific phospholipase C (PC-PLC), the enzyme involved in cell differentiation and proliferation, has not yet been explored in tumor initiating cells (TICs). We investigated PC-PLC expression and effects of PC-PLC inhibition in two adherent (AD) squamous carcinoma cell lines (A431 and CaSki), with different proliferative and stemness potential, and in TIC-enriched floating spheres (SPH) originated from them. Results Compared with immortalized non-tumoral keratinocytes (HaCaT) A431-AD cells showed 2.5-fold higher PC-PLC activity, nuclear localization of a 66-kDa PC-PLC isoform, but a similar distribution of the enzyme on plasma membrane and in cytoplasmic compartments. Compared with A431-AD, A431-SPH cells showed about 2.8-fold lower PC-PLC protein and activity levels, but similar nuclear content. Exposure of adherent cells to the PC-PLC inhibitor D609 (48h) induced a 50% reduction of cell proliferation at doses comprised between 33 and 50 μg/ml, without inducing any relevant cytotoxic effect (cell viability 95±5%). In A431-SPH and CaSki-SPH D609 induced both cytostatic and cytotoxic effects at about 20 to 30-fold lower doses (IC50 ranging between 1.2 and 1.6 μg/ml). Furthermore, D609 treatment of A431-AD and CaSki-AD cells affected the sphere-forming efficiency, which dropped in both cells, and induced down-modulation of stem-related markers mRNA levels (Oct4, Nestin, Nanog and ALDH1 in A431; Nestin and ALDH1 in CaSki cells). Conclusions These data suggest that the inhibition of PC-PLC activity may represent a new therapeutic approach to selectively target the most aggressive and tumor promoting sub-population of floating spheres originated from squamous cancer cells possessing different proliferative and stemness potential. PMID:26402860

  19. Squamous cell carcinoma - invasive (image)

    MedlinePlus

    This irregular red nodule is an invasive squamous cell carcinoma (a form of skin cancer). Initial appearance, shown here, may be very similar to a noncancerous growth called a keratoacanthoma. Squamous cell cancers ...

  20. 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.

  1. Protein-tyrosine-phosphatase-mediated epidermal growth factor (EGF) receptor transinactivation and EGF receptor-independent stimulation of mitogen-activated protein kinase by bradykinin in A431 cells.

    PubMed Central

    Graness, A; Hanke, S; Boehmer, F D; Presek, P; Liebmann, C

    2000-01-01

    Transactivation of the epidermal growth factor (EGF) receptor (EGFR) has been proposed to represent an essential link between G-protein-coupled receptors and the mitogen-activated protein kinase (MAPK) pathway in various cell types. In the present work we report, in contrast, that in A431 cells bradykinin transinactivates the EGFR and stimulates MAPK activity independently of EGFR tyrosine phosphorylation. Both effects of bradykinin are mediated by a pertussis-toxin-insensitive G-protein. Three lines of evidence suggest the activation of a protein tyrosine phosphatase (PTP) by bradykinin: (i) treatment of A431 cells with bradykinin decreases both basal and EGF-induced EGFR tyrosine phosphorylation, (ii) this effect of bradykinin can be blocked by two different PTP inhibitors, and (iii) bradykinin significantly increased the PTP activity in total A431 cell lysates when measured in vitro. The transmembrane receptor PTP sigma was identified as a putative mediator of bradykinin-induced downregulation of EGFR autophosphorylation. Activation of MAPK in response to bradykinin was insensitive towards AG 1478, a specific inhibitor of EGFR tyrosine kinase, but was blocked by wortmannin or bisindolylmaleimide, inhibitors of phosphatidylinositol 3-kinase (PI3-K) and protein kinase C (PKC) respectively. These results also suggest that the bradykinin-induced activation of MAPK is independent of EGFR and indicate a pathway involving PI3-K and PKC. In addition, bradykinin evokes a rapid and transient increase in Src kinase activity. Although Src does not participate in bradykinin-induced stimulation of PTP activity, inhibition of Src by 4-amino-5-(4-methylphenyl)-7-(t-butyl)pyrazolo(3,4-d)pyrimidine leads to an increase in MAPK activation by bradykinin. Our results suggest that in A431 cells the G(q/11)-protein-coupled bradykinin B(2) receptor may stimulate PTP activity and thereby transinactivate the EGFR, and may simultaneously activate MAPK by an alternative signalling pathway

  2. [Penile squamous cell carcinoma].

    PubMed

    Ferrándiz-Pulido, C; de Torres, I; García-Patos, V

    2012-01-01

    Penile squamous cell carcinoma (SCC) is uncommon in Europe, where it accounts for approximately 0.7% of all malignant tumors in men. The main risk factors are poor hygiene, lack of circumcision, human papillomavirus (HPV) infection, and certain chronic inflammatory skin diseases. HPV infection is detected in 70% to 100% of all penile in situ SCCs and in 30% to 50% of invasive forms of the disease, mainly basaloid and warty SCCs. In situ tumors can be treated conservatively, but close monitoring is essential as they become invasive in between 1% and 30% of cases. The treatment of choice for penile SCC is surgery. Inguinal lymph node irradiation is no longer recommended as a prophylactic measure, and it appears that selective lymph node biopsy might be useful for reducing the morbidity associated with prophylactic inguinal lymph node dissection. Survival is directly related to lymph node involvement. Improving our knowledge of underlying molecular changes and their associated genotypes will open up new therapeutic pathways. Copyright © 2011 Elsevier España, S.L. and AEDV. All rights reserved.

  3. Metastasis suppressor proteins in cutaneous squamous cell carcinoma.

    PubMed

    Bozdogan, Onder; Vargel, Ibrahim; Cavusoglu, Tarik; Karabulut, Ayse A; Karahan, Gurbet; Sayar, Nilufer; Atasoy, Pınar; Yulug, Isik G

    2016-07-01

    Cutaneous squamous cell carcinomas (cSCCs) are common human carcinomas. Despite having metastasizing capacities, they usually show less aggressive progression compared to squamous cell carcinoma (SCC) of other organs. Metastasis suppressor proteins (MSPs) are a group of proteins that control and slow-down the metastatic process. In this study, we established the importance of seven well-defined MSPs including NDRG1, NM23-H1, RhoGDI2, E-cadherin, CD82/KAI1, MKK4, and AKAP12 in cSCCs. Protein expression levels of the selected MSPs were detected in 32 cSCCs, 6 in situ SCCs, and two skin cell lines (HaCaT, A-431) by immunohistochemistry. The results were evaluated semi-quantitatively using the HSCORE system. In addition, mRNA expression levels were detected by qRT-PCR in the cell lines. The HSCOREs of NM23-H1 were similar in cSCCs and normal skin tissues, while RGHOGDI2, E-cadherin and AKAP12 were significantly downregulated in cSCCs compared to normal skin. The levels of MKK4, NDRG1 and CD82 were partially conserved in cSCCs. In stage I SCCs, nuclear staining of NM23-H1 (NM23-H1nuc) was significantly lower than in stage II/III SCCs. Only nuclear staining of MKK4 (MKK4nuc) showed significantly higher scores in in situ carcinomas compared to invasive SCCs. In conclusion, similar to other human tumors, we have demonstrated complex differential expression patterns for the MSPs in in-situ and invasive cSCCs. This complex MSP signature warrants further biological and experimental pathway research. Copyright © 2016 Elsevier GmbH. All rights reserved.

  4. General Information about Merkel Cell Carcinoma

    MedlinePlus

    ... Merkel Cell Carcinoma Treatment (PDQ®)–Patient Version General Information About Merkel Cell Carcinoma Go to Health Professional ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

  5. Potential targets for lung squamous cell carcinoma

    Cancer.gov

    Researchers have identified potential therapeutic targets in lung squamous cell carcinoma, the second most common form of lung cancer. The Cancer Genome Atlas (TCGA) Research Network study comprehensively characterized the lung squamous cell carcinoma gen

  6. Treatment Options by Stage (Merkel Cell Carcinoma)

    MedlinePlus

    ... of Skin Cancer Skin Cancer Screening Research Merkel Cell Carcinoma Treatment (PDQ®)–Patient Version General Information About Merkel Cell Carcinoma Go to Health Professional Version Key Points ...

  7. Treatment Option Overview (Merkel Cell Carcinoma)

    MedlinePlus

    ... of Skin Cancer Skin Cancer Screening Research Merkel Cell Carcinoma Treatment (PDQ®)–Patient Version General Information About Merkel Cell Carcinoma Go to Health Professional Version Key Points ...

  8. Multiple gastrointestinal metastases of Merkel cell carcinoma.

    PubMed

    Poškus, Eligijus; Platkevičius, Gediminas; Simanskaitė, Vilma; Rimkevičiūtė, Ernesta; Petrulionis, Marius; Strupas, Kestutis

    2016-01-01

    Merkel cell carcinoma is an aggressive skin malignancy. Primary Merkel cell carcinomas are treated by wide radical excision with or without adjuvant radiotherapy, while benefits of adjuvant chemotherapy remain doubtful. There are only several cases of gastrointestinal metastases of Merkel cell carcinoma reported so far. We report a case of recurrent Merkel cell carcinoma with metastases to the stomach and the small intestines after wide excision of primary Merkel cell carcinoma. Copyright © 2016 The Lithuanian University of Health Sciences. Production and hosting by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  9. Familial Non-VHL Clear Cell Renal Cell Carcinoma

    MedlinePlus

    ... Cell Carcinoma Request Permissions Familial Non-VHL Clear Cell Renal Cell Carcinoma Approved by the Cancer.Net Editorial Board , 12/2017 What is familial non-VHL clear cell renal cell carcinoma? Familial non-VHL clear cell ...

  10. Renal cell carcinoma

    MedlinePlus

    Renal cancer; Kidney cancer; Hypernephroma; Adenocarcinoma of renal cells; Cancer - kidney ... 2016:chap 57. National Cancer Institute website. Renal cell cancer treatment (PDQ) - health professional version. February 23, 2018. ...

  11. Update on Merkel Cell Carcinoma.

    PubMed

    Harms, Paul W

    2017-09-01

    Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous neuroendocrine malignancy. Merkel cell polyomavirus, a tumorigenic DNA virus, is present in most MCC tumors, with implications for tumor biology, diagnosis, and management. Merkel cell polyomavirus-negative tumors have a high burden of UV-signature mutations, similar to melanoma. The histopathologic diagnosis of MCC requires immunohistochemistry to exclude morphologically similar entities. Therapies for advanced disease are currently lacking. Here, the features of MCC are reviewed, including recent molecular discoveries with implications for improved therapy for advanced disease. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Merkel cell carcinoma in an immunosuppressed patient.

    PubMed

    Góes, Heliana Freitas de Oliveira; Lima, Caren Dos Santos; Issa, Maria Cláudia de Almeida; Luz, Flávio Barbosa; Pantaleão, Luciana; Paixão, José Gabriel Miranda da

    2017-01-01

    Merkel cell carcinoma is an uncommon neuroendocrine carcinoma with a rising incidence and an aggressive behavior. It predominantly occurs in older patients, with onset occurring at a mean age of 75-80 years. Recognized risk factors are ultraviolet sunlight exposure, immunosuppression, and, more recently, Merkel cell polyomavirus. We report a case of Merkel cell carcinoma in a young HIV positive patient with Merkel Cell polyomavirus detected in the tumor.

  13. Basal cell carcinoma

    MedlinePlus

    ... confirm basal cell cancer or other skin cancers. Treatment Treatment depends on the size, depth, and location ... blocks both UVA and UVB light. Use a water-resistant sunscreen. Apply sunscreen at least 30 minutes ...

  14. Photodynamic therapy for basal cell carcinoma.

    PubMed

    Fargnoli, Maria Concetta; Peris, Ketty

    2015-11-01

    Topical photodynamic therapy is an effective and safe noninvasive treatment for low-risk basal cell carcinoma, with the advantage of an excellent cosmetic outcome. Efficacy of photodynamic therapy in basal cell carcinoma is supported by substantial research and clinical trials. In this article, we review the procedure, indications and clinical evidences for the use of photodynamic therapy in the treatment of basal cell carcinoma.

  15. Bowenoid epidermotropic metastatic squamous cell carcinoma.

    PubMed

    Ihm, C W; Park, S L; Sung, S Y; Lee, I S

    1996-10-01

    Epidermotropic metastatic squamous cell carcinoma produced full-thickness cellular atypia of bowenoid carcinoma in situ or vulvar intraepithelial neoplasia, grade 3 (VIN 3), in a 73-year-old woman who had past history of uterine cervical carcinoma. The presence of intravascular tumor cell nests and areas showing smooth continuity of the malignant squamous cell nodules with the adjoining benign epidermis supported the possibility of the epidermotropic metastasis. To our knowledge, metastatic epidermotropic squamous carcinoma clinicopathologically simulating primary Bowen's disease has not been reported.

  16. Current Aspects on Oral Squamous Cell Carcinoma

    PubMed Central

    Markopoulos, Anastasios K

    2012-01-01

    Oral squamous cell carcinoma is the most common malignant epithelial neoplasm affecting the oral cavity. This article overviews the essential points of oral squamous cell carcinoma, highlighting its risk and genomic factors, the potential malignant disorders and the therapeutic approaches. It also emphasizes the importance of the early diagnosis. PMID:22930665

  17. Scalp squamous cell carcinoma in xeroderma pigmentosum.

    PubMed

    Awan, Basim A; Alzanbagi, Hanadi; Samargandi, Osama A; Ammar, Hossam

    2014-02-01

    Xeroderma pigmentosum is a rare autosomal-recessive disorder that appears in early childhood. Squamous cell carcinoma is not uncommon in patients with xeroderma pigmentosum and mostly involving the face, head, neck, and scalp. However, squamous cell carcinoma of the scalp may exhibit an aggressive course. Here, we present a huge squamous cell carcinoma of the scalp in a three-years-old child with xeroderma pigmentosum. In addition, we illustrate the challenges of a child with xeroderma pigmentosum who grows up in a sunny environment where the possibility of early onset of squamous cell carcinoma is extremely high in any suspected skin lesion. In xeroderma pigmentosum patients, squamous cell carcinoma of the scalp can present early and tends to be unusually aggressive. In sunny areas, proper education to the patient and their parents about ultra-violet light protection and early recognition of any suspicious lesion could be life-saving.

  18. Scalp Squamous Cell Carcinoma in Xeroderma Pigmentosum

    PubMed Central

    Awan, Basim A.; Alzanbagi, Hanadi; Samargandi, Osama A.; Ammar, Hossam

    2014-01-01

    Context: Xeroderma pigmentosum is a rare autosomal-recessive disorder that appears in early childhood. Squamous cell carcinoma is not uncommon in patients with xeroderma pigmentosum and mostly involving the face, head, neck, and scalp. However, squamous cell carcinoma of the scalp may exhibit an aggressive course. Case Report: Here, we present a huge squamous cell carcinoma of the scalp in a three-years-old child with xeroderma pigmentosum. In addition, we illustrate the challenges of a child with xeroderma pigmentosum who grows up in a sunny environment where the possibility of early onset of squamous cell carcinoma is extremely high in any suspected skin lesion. Conclusion: In xeroderma pigmentosum patients, squamous cell carcinoma of the scalp can present early and tends to be unusually aggressive. In sunny areas, proper education to the patient and their parents about ultra-violet light protection and early recognition of any suspicious lesion could be life-saving. PMID:24695441

  19. Mucinous breast carcinoma with tall columnar cells.

    PubMed

    Tsoukalas, N; Kiakou, M; Tolia, M; Kostakis, I D; Galanopoulos, M; Nakos, G; Tryfonopoulos, D; Kyrgias, G; Koumakis, G

    2018-05-01

    Mucinous carcinoma of the breast represents 1%-4% of all breast cancers. The World Health Organization classification divides this type of tumour into three different subtypes: mucinous carcinoma, mucinous carcinoma with tall columnar cells (mucinous cystadenocarcinoma and columnar cell mucinous carcinoma) and signet ring cell carcinoma. A 74-year-old woman presented a tumour with inflammatory features in the upper outer quadrant of her left breast, 7 cm in diameter. The core biopsy showed infiltrating ductal carcinoma of no specific type. The tumour-node-metastasis clinical staging was T4cN3M0 (Stage IIIC). She received neoadjuvant chemotherapy, underwent left mastectomy with radical axillary resection and subsequently received radiotherapy and chemotherapy. The histological examination of the surgical specimen revealed two solid tumors in the tail of Spence, which corresponded to adenocarcinoma with high columnar cells. The patient died 16 months after the diagnosis, suffering from pulmonary metastases and anterior chest wall infiltration. A review of the literature revealed only 21 reports of mucinous carcinoma of the breast with tall columnar cells, including our case. This is only the third time that the specific histological type of columnar cell mucinous carcinoma has been reported in the literature.

  20. Photosensitizer adhered to cell culture microplates induces phototoxicity in carcinoma cells.

    PubMed

    Ziegler, Verena; Kiesslich, Tobias; Krammer, Barbara; Plaetzer, Kristjan

    2013-01-01

    In vitro experiments in plastic receptacles are the basis of characterization of new photosensitizers (PSs) for the photodynamic therapy. We recently reported that lipophilic PSs adhere to cell culture microplates in a kinetic-like manner (Engelhardt et al., 2011). In the current study, we examined the interaction and phototoxic effects of the microplate-adhered PS in cancer cells. Therefore, we preloaded microplates with hypericin, Foscan, PVP-hypericin, or aluminum (III) phthalocyanine tetrasulfonate chloride (AlPCS4) for 24 hours and measured the PS distribution after addition of A431 human carcinoma cells: following another 24 hours up to 68% of hypericin were detected in the cell fraction. The hydrophilic PVP-hypericin and AlPCS4 also diffused into the cells, but the quantities of PS adherence were considerably lower. Microplate-adhered Foscan appeared not to be redistributed. In contrast to the hydrophilic PSs, the cellular phototoxicity of microplate-adhered lipophilic PS was high, independent of whether the PS (i) was pre-loaded onto microplates or (ii) added simultaneously with the cells or (iii) one day after cell seeding. Based on these results, we suggest testing lipophilic PS dyes for their adherence to microplates. Furthermore, the ability of plastic materials to (reversibly) store PSs might represent a new approach for the PS delivery or the development of antimicrobial coatings.

  1. Photosensitizer Adhered to Cell Culture Microplates Induces Phototoxicity in Carcinoma Cells

    PubMed Central

    Ziegler, Verena; Kiesslich, Tobias; Krammer, Barbara; Plaetzer, Kristjan

    2013-01-01

    In vitro experiments in plastic receptacles are the basis of characterization of new photosensitizers (PSs) for the photodynamic therapy. We recently reported that lipophilic PSs adhere to cell culture microplates in a kinetic-like manner (Engelhardt et al., 2011). In the current study, we examined the interaction and phototoxic effects of the microplate-adhered PS in cancer cells. Therefore, we preloaded microplates with hypericin, Foscan, PVP-hypericin, or aluminum (III) phthalocyanine tetrasulfonate chloride (AlPCS4) for 24 hours and measured the PS distribution after addition of A431 human carcinoma cells: following another 24 hours up to 68% of hypericin were detected in the cell fraction. The hydrophilic PVP-hypericin and AlPCS4 also diffused into the cells, but the quantities of PS adherence were considerably lower. Microplate-adhered Foscan appeared not to be redistributed. In contrast to the hydrophilic PSs, the cellular phototoxicity of microplate-adhered lipophilic PS was high, independent of whether the PS (i) was pre-loaded onto microplates or (ii) added simultaneously with the cells or (iii) one day after cell seeding. Based on these results, we suggest testing lipophilic PS dyes for their adherence to microplates. Furthermore, the ability of plastic materials to (reversibly) store PSs might represent a new approach for the PS delivery or the development of antimicrobial coatings. PMID:23509741

  2. Merkel cell carcinoma: is this a true carcinoma?

    PubMed

    Jankowski, Marek; Kopinski, Piotr; Schwartz, Robert; Czajkowski, Rafal

    2014-11-01

    Recent years have brought an enhanced understanding of Merkel cell carcinoma (MCC) biology, especially with regard to the Merkel cell polyoma virus as a causative agent. Differences between Merkel cell polyomavirus-positive and Merkel cell polyomavirus-negative MCC in morphology; gene expression, miRNA profiles and prognosis have been reported. Origin of MCC is controversial. Presence of neurosecretory granules has suggested that these carcinomas originate from one of the neurocrest derivatives, most probably Merkel cells; the name Merkel cell carcinoma is now widely accepted. Expression of PGP 9.5, chromogranin A and several neuropeptides, initially regarded as specific markers for neural and neuroendocrine cells, has recently been shown in a subset of lymphomas. MCC commonly expresses terminal deoxynucleotidyl transferase and PAX5. Their co-expression under physiologic circumstances is restricted to pro/pre-B cells and pre-B cells. These findings lead to the hypothesis by zur Hausen et al. that MCC originates from early B cells. This review was intended to critically appraise zur Hausen's hypothesis and discuss the possibility that MCC is a heterogenous entity with distinct subtypes. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. Nevoid Basal Cell Carcinoma Syndrome (Gorlin Syndrome).

    PubMed

    Bresler, Scott C; Padwa, Bonnie L; Granter, Scott R

    2016-06-01

    Nevoid basal cell carcinoma syndrome, or basal cell nevus syndrome (Gorlin syndrome), is a rare autosomal dominantly inherited disorder that is characterized by development of basal cell carcinomas from a young age. Other distinguishing clinical features are seen in a majority of patients, and include keratocystic odontogenic tumors (formerly odontogenic keratocysts) as well as dyskeratotic palmar and plantar pitting. A range of skeletal and other developmental abnormalities are also often seen. The disorder is caused by defects in hedgehog signaling which result in constitutive pathway activity and tumor cell proliferation. As sporadic basal cell carcinomas also commonly harbor hedgehog pathway aberrations, therapeutic agents targeting key signaling constituents have been developed and tested against advanced sporadically occurring tumors or syndromic disease, leading in 2013 to FDA approval of the first hedgehog pathway-targeted small molecule, vismodegib. The elucidation of the molecular pathogenesis of nevoid basal cell carcinoma syndrome has resulted in further understanding of the most common human malignancy.

  4. Chemotherapeutic Effect of CD147 Antibody-labeled Micelles Encapsulating Doxorubicin Conjugate Targeting CD147-Expressing Carcinoma Cells.

    PubMed

    Asakura, Tadashi; Yokoyama, Masayuki; Shiraishi, Koichi; Aoki, Katsuhiko; Ohkawa, Kiyoshi

    2018-03-01

    CD147 (basigin/emmprin) is expressed on the surface of carcinoma cells. For studying the efficacy of CD147-targeting medicine on CD147-expressing cells, we studied the effect of anti-CD147-labeled polymeric micelles (CD147ab micelles) that encapsulated a conjugate of doxorubicin with glutathione (GSH-DXR), with specific accumulation and cytotoxicity against CD147-expressing A431 human epidermoid carcinoma cells, Ishikawa human endometrial adenocarcinoma cells, and PC3 human prostate carcinoma cells. By treatment of each cell type with CD147ab micelles for 1 h, a specific accumulation of CD147ab micelles in CD147-expressing cells was observed. In addition, the cytotoxicity of GSH-DXR-encapsulated micelles against each cell type was measured by treatment of the micelles for 1 h. The cytotoxic effect of CD147ab micelles carrying GSH-DXR was 3- to 10-fold higher for these cells than that of micelles without GSH-DXR. These results suggest that GSH-DXR-encapsulated CD147ab micelles could serve as an effective drug delivery system to CD147-expressing carcinoma cells. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  5. Basal cell carcinoma, squamous cell carcinoma and melanoma of the head and face.

    PubMed

    Feller, L; Khammissa, R A G; Kramer, B; Altini, M; Lemmer, J

    2016-02-05

    Ultraviolet light (UV) is an important risk factor for cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma and cutaneous melanoma of the skin. These cancers most commonly affect persons with fair skin and blue eyes who sunburn rather than suntan. However, each of these cancers appears to be associated with a different pattern of UV exposure and to be mediated by different intracellular molecular pathways.Some melanocortin 1 receptor (MC1R) gene variants play a direct role in the pathogenesis of cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma and cutaneous melanoma apart from their role in determining a cancer-prone pigmentory phenotype (fair skin, red hair, blue eyes) through their interactions with other genes regulating immuno-inflammatory responses, DNA repair or apoptosis.In this short review we focus on the aetiological role of UV in cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma and cutaneous melanoma of the skin, and on some associated biopathological events.

  6. Apigenin inhibits renal cell carcinoma cell proliferation

    PubMed Central

    Meng, Shuai; Zhu, Yi; Li, Jiang-Feng; Wang, Xiao; Liang, Zhen; Li, Shi-Qi; Xu, Xin; Chen, Hong; Liu, Ben; Zheng, Xiang-Yi; Xie, Li-Ping

    2017-01-01

    Apigenin, a natural flavonoid found in vegetables and fruits, has antitumor activity in several cancer types. The present study evaluated the effects and mechanism of action of apigenin in renal cell carcinoma (RCC) cells. We found that apigenin suppressed ACHN, 786-0, and Caki-1 RCC cell proliferation in a dose- and time-dependent manner. A comet assay suggested that apigenin caused DNA damage in ACHN cells, especially at higher doses, and induced G2/M phase cell cycle arrest through ATM signal modulation. Small interfering RNA (siRNA)-mediated p53 knockdown showed that apigenin-induced apoptosis was likely p53 dependent. Apigenin anti-proliferative effects were confirmed in an ACHN cell xenograft mouse model. Apigenin treatment reduced tumor growth and volume in vivo, and immunohistochemical staining revealed lower Ki-67 indices in tumors derived from apigenin-treated mice. These findings suggest that apigenin exposure induces DNA damage, G2/M phase cell cycle arrest, p53 accumulation and apoptosis, which collectively suppress ACHN RCC cell proliferation in vitro and in vivo. Given its antitumor effects and low in vivo toxicity, apigenin is a highly promising agent for treatment of RCC. PMID:28423637

  7. Apigenin inhibits renal cell carcinoma cell proliferation.

    PubMed

    Meng, Shuai; Zhu, Yi; Li, Jiang-Feng; Wang, Xiao; Liang, Zhen; Li, Shi-Qi; Xu, Xin; Chen, Hong; Liu, Ben; Zheng, Xiang-Yi; Xie, Li-Ping

    2017-03-21

    Apigenin, a natural flavonoid found in vegetables and fruits, has antitumor activity in several cancer types. The present study evaluated the effects and mechanism of action of apigenin in renal cell carcinoma (RCC) cells. We found that apigenin suppressed ACHN, 786-0, and Caki-1 RCC cell proliferation in a dose- and time-dependent manner. A comet assay suggested that apigenin caused DNA damage in ACHN cells, especially at higher doses, and induced G2/M phase cell cycle arrest through ATM signal modulation. Small interfering RNA (siRNA)-mediated p53 knockdown showed that apigenin-induced apoptosis was likely p53 dependent. Apigenin anti-proliferative effects were confirmed in an ACHN cell xenograft mouse model. Apigenin treatment reduced tumor growth and volume in vivo, and immunohistochemical staining revealed lower Ki-67 indices in tumors derived from apigenin-treated mice. These findings suggest that apigenin exposure induces DNA damage, G2/M phase cell cycle arrest, p53 accumulation and apoptosis, which collectively suppress ACHN RCC cell proliferation in vitro and in vivo. Given its antitumor effects and low in vivo toxicity, apigenin is a highly promising agent for treatment of RCC.

  8. Cetuximab & Nivolumab in Patients With Recurrent/Metastatic Head & Neck Squamous Cell Carcinoma

    ClinicalTrials.gov

    2018-06-13

    Squamous Cell Carcinoma of the Oropharynx; Squamous Cell Carcinoma of the Larynx; Squamous Cell Carcinoma of the Oral Cavity; Squamous Cell Carcinoma of the Hypopharynx; Squamous Cell Carcinoma of the Paranasal Sinus; Head and Neck Squamous Cell Carcinoma; Squamous Cell Cancer; Head and Neck Carcinoma

  9. Perioperative Considerations in Metastatic Renal Cell Carcinoma

    PubMed Central

    Flavin, Kate; Vasdev, Nikhil; Ashead, Jim; Lane, Tim; Hanbury, Damian; Nathan, Paul; Gowrie-Mohan, Shanmugasundaram

    2016-01-01

    Patients with metastatic renal cell carcinoma are complex, with the potential for significant complications, and require extensive pre-, peri-, and postoperative management. This article discusses, in depth, the necessary considerations in the treatment of these patients. PMID:27833463

  10. Sunitinib benefits patients with renal cell carcinoma

    Cancer.gov

    Findings from clinical trial patients with metastatic renal cell carcinoma, a common kidney cancer, show they did not have accelerated tumor growth after treatment with sunitinib, in contrast to some study results in animals.

  11. Metastatic Basal Cell Carcinoma Accompanying Gorlin Syndrome

    PubMed Central

    Bilir, Yeliz; Gokce, Erkan; Ozturk, Banu; Deresoy, Faik Alev; Yuksekkaya, Ruken; Yaman, Emel

    2014-01-01

    Gorlin-Goltz syndrome or basal cell nevus syndrome is an autosomal dominant syndrome characterized by skeletal anomalies, numerous cysts observed in the jaw, and multiple basal cell carcinoma of the skin, which may be accompanied by falx cerebri calcification. Basal cell carcinoma is the most commonly skin tumor with slow clinical course and low metastatic potential. Its concomitance with Gorlin syndrome, resulting from a mutation in a tumor suppressor gene, may substantially change morbidity and mortality. A 66-year-old male patient with a history of recurrent basal cell carcinoma was presented with exophthalmus in the left eye and the lesions localized in the left lateral orbita and left zygomatic area. His physical examination revealed hearing loss, gapped teeth, highly arched palate, and frontal prominence. Left orbital mass, cystic masses at frontal and ethmoidal sinuses, and multiple pulmonary nodules were detected at CT scans. Basal cell carcinoma was diagnosed from biopsy of ethmoid sinus. Based on the clinical and typical radiological characteristics (falx cerebri calcification, bifid costa, and odontogenic cysts), the patient was diagnosed with metastatic skin basal cell carcinoma accompanied by Gorlin syndrome. Our case is a basal cell carcinoma with aggressive course accompanying a rarely seen syndrome. PMID:25506011

  12. Metastatic Basal cell carcinoma accompanying gorlin syndrome.

    PubMed

    Bilir, Yeliz; Gokce, Erkan; Ozturk, Banu; Deresoy, Faik Alev; Yuksekkaya, Ruken; Yaman, Emel

    2014-01-01

    Gorlin-Goltz syndrome or basal cell nevus syndrome is an autosomal dominant syndrome characterized by skeletal anomalies, numerous cysts observed in the jaw, and multiple basal cell carcinoma of the skin, which may be accompanied by falx cerebri calcification. Basal cell carcinoma is the most commonly skin tumor with slow clinical course and low metastatic potential. Its concomitance with Gorlin syndrome, resulting from a mutation in a tumor suppressor gene, may substantially change morbidity and mortality. A 66-year-old male patient with a history of recurrent basal cell carcinoma was presented with exophthalmus in the left eye and the lesions localized in the left lateral orbita and left zygomatic area. His physical examination revealed hearing loss, gapped teeth, highly arched palate, and frontal prominence. Left orbital mass, cystic masses at frontal and ethmoidal sinuses, and multiple pulmonary nodules were detected at CT scans. Basal cell carcinoma was diagnosed from biopsy of ethmoid sinus. Based on the clinical and typical radiological characteristics (falx cerebri calcification, bifid costa, and odontogenic cysts), the patient was diagnosed with metastatic skin basal cell carcinoma accompanied by Gorlin syndrome. Our case is a basal cell carcinoma with aggressive course accompanying a rarely seen syndrome.

  13. Merkel Cell Carcinoma Therapeutic Update.

    PubMed

    Cassler, Nicole M; Merrill, Dean; Bichakjian, Christopher K; Brownell, Isaac

    2016-07-01

    Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine tumor of the skin. Early-stage disease can be cured with surgical resection and radiotherapy (RT). Sentinel lymph node biopsy (SLNB) is an important staging tool, as a microscopic MCC is frequently identified. Adjuvant RT to the primary excision site and regional lymph node bed may improve locoregional control. However, newer studies confirm that patients with biopsy-negative sentinel lymph nodes may not benefit from regional RT. Advanced MCC currently lacks a highly effective treatment as responses to chemotherapy are not durable. Recent work suggests that immunotherapy targeting the programmed cell death receptor 1/programmed cell death ligand 1 (PD-1/PD-L1) checkpoint holds great promise in treating advanced MCC and may provide durable responses in a portion of patients. At the same time, high-throughput sequencing studies have demonstrated significant differences in the mutational profiles of tumors with and without the Merkel cell polyomavirus (MCV). An important secondary endpoint in the ongoing immunotherapy trials for MCC will be determining if there is a response difference between the virus-positive MCC tumors that typically lack a large mutational burden and the virus-negative tumors that have a large number of somatic mutations and predicted tumor neoantigens. Interestingly, sequencing studies have failed to identify a highly recurrent activated driver pathway in the majority of MCC tumors. This may explain why targeted therapies can demonstrate exceptional responses in case reports but fail when treating all comers with MCC. Ultimately, a precision medicine approach may be more appropriate for treating MCC, where identified driver mutations are used to direct targeted therapies. At a minimum, stratifying patients in future clinical trials based on tumor viral status should be considered as virus-negative tumors are more likely to harbor activating driver mutations.

  14. Merkel cell polyomavirus and Merkel cell carcinoma.

    PubMed

    DeCaprio, James A

    2017-10-19

    Merkel cell polyomavirus (MCPyV) causes the highly aggressive and relatively rare skin cancer known as Merkel cell carcinoma (MCC). MCPyV also causes a lifelong yet relatively innocuous infection and is one of 14 distinct human polyomaviruses species. Although polyomaviruses typically do not cause illness in healthy individuals, several can cause catastrophic diseases in immunocompromised hosts. MCPyV is the only polyomavirus clearly associated with human cancer. How MCPyV causes MCC and what oncogenic events must transpire to enable this virus to cause MCC is the focus of this essay.This article is part of the themed issue 'Human oncogenic viruses'. © 2017 The Author(s).

  15. 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.

  16. Conditioned media from a renal cell carcinoma cell line demonstrates the presence of basic fibroblast growth factor.

    PubMed

    Mydlo, J H; Zajac, J; Macchia, R J

    1993-09-01

    In a previous report, we demonstrated the isolation and purification of a heparin binding growth factor from human renal carcinoma, and suggested that this growth factor may play a role in the neovascularity and growth of the tumor. In this report, we demonstrate that the growth of the renal cell carcinoma cell line RC29 is stimulated by the addition of exogenous fibroblast growth factor (FGF), epidermal growth factor (EGF) and transforming growth factor alpha (TGF alpha). Also, media conditioned by this cell line was able to stimulate growth of the A431 vulvar tumor cell line, known for its high concentration of EGF receptors, 3T3 fibroblasts, human umbilical vein (HUV) cells and RC29 cells. Using heparin-sepharose chromatography and then SDS polyacrylamide gel electrophoresis (PAGE), we were able to demonstrate several proteins in the conditioned media of the RC29 cell line. Using Western blot analysis, we detected that at least one of the proteins expressed in this conditioned media was FGF and that it belongs to the basic, not acidic, family of fibroblast growth factors. These findings suggest that renal tumors may express growth factors that may play a direct role in maintaining their unrestricted proliferation.

  17. Metastatic giant basal cell carcinoma: a case report.

    PubMed

    Bellahammou, Khadija; Lakhdissi, Asmaa; Akkar, Othman; Rais, Fadoua; Naoual, Benhmidou; Elghissassi, Ibrahim; M'rabti, Hind; Errihani, Hassan

    2016-01-01

    Basal cell carcinoma is the most common skin cancer, characterised by a slow growing behavior, metastasis are extremely rare, and it occurs in less than 0, 1% of all cases. Giant basal cell carcinoma is a rare form of basal cell carcinoma, more aggressive and defined as a tumor measuring more than 5 cm at its largest diameter. Only 1% of all basal cell carcinoma develops to a giant basal cell carcinoma, resulting of patient's negligence. Giant basal cell carcinoma is associated with higher potential of metastasis and even death, compared to ordinary basal cell carcinoma. We report a case of giant basal cell carcinoma metastaticin lung occurring in a 79 years old male patient, with a fatal evolution after one course of systemic chemotherapy. Giant basal cell carcinoma is a very rare entity, early detection of these tumors could prevent metastasis occurrence and improve the prognosis of this malignancy.

  18. Metastatic renal cell carcinoma in the nasopharynx.

    PubMed

    Atar, Yavuz; Topaloglu, Ilhan; Ozcan, Deniz

    2013-01-01

    Metastatic renal cell carcinoma of the nasopharynx, nasal cavity, and paranasal sinuses can be misdiagnosed as primary malignant or benign diseases. A 33-year-old male attended our outpatient clinic complaining of difficulty breathing through the nose, bloody nasal discharge, postnasal drop, snoring, and discharge of phlegm. Endoscopic nasopharyngeal examination showed a vascularized nasopharyngeal mass. Under general anesthesia, multiple punch biopsies were taken from the nasopharynx. Pathologically, the tumor cells had clear cytoplasm and were arranged in a trabecular pattern lined by a layer of endothelial cells. After the initial pathological examination, the pathologist requested more information about the patient's clinical status. A careful history revealed that the patient had undergone left a nephrectomy for a kidney mass diagnosed as renal cell carcinoma 3 years earlier. Subsequently, nasopharyngeal metastatic renal cell carcinoma was diagnosed by immunohistochemical staining with CD10 and vimentin. Radiotherapy was recommended for treatment.

  19. Small cell type neuroendocrine carcinoma colliding with squamous cell carcinoma at esophagus

    PubMed Central

    Yang, Luoluo; Sun, Xun; Zou, Yabin; Meng, Xiangwei

    2014-01-01

    Collision tumor is an extremely rare tumor which defined as the concrescence of two distinct primaries neoplasms. We report here a case of collision tumor at lower third esophagus composed of small cell type neuroendocrine carcinoma (NEC), which is an very rare, highly aggressive and poorly prognostic carcinoma and squamous cell carcinoma (SqCC). In our case, pathologically, the small cell carcinoma display the characteristic of small, round, ovoid or spindle-shaped tumor cells with scant cytoplasm, which colliding with a moderately differentiated squamous cell carcinoma. Immunohistochemical staining demonstrated positive activities for CD56, synaptophysin, 34βE12, CK 5/6, ki-67 (70%-80%), but negative for CD99, chromogranin A, and TTF-1. Accurate diagnosis was made base on these findings. PMID:24817981

  20. 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.

  1. 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

  2. Clinicopathological characteristics of head and neck Merkel cell carcinomas.

    PubMed

    Knopf, Andreas; Bas, Murat; Hofauer, Benedikt; Mansour, Naglaa; Stark, Thomas

    2017-01-01

    There are still controversies about the therapeutic strategies and subsequent outcome in head and neck Merkel cell carcinoma. Clinicopathological data of 23 Merkel cell carcinomas, 93 cutaneous head and neck squamous cell carcinomas (HNSCCs), 126 malignant melanomas, and 91 primary parotid gland carcinomas were comprehensively analyzed. Merkel cell carcinomas were cytokeratin 20 (CK20)/neuron-specific enolase (NSE)/chromogranin A (CgA)/synaptophysin (Syn)/thyroid transcription factor-1 (TTF-1)/MIB1 immunostained. All Merkel cell carcinomas underwent wide local excision. Parotidectomy/neck dissection was performed in 40%/33% cutaneous Merkel cell carcinoma and 100%/100% in parotid gland Merkel cell carcinoma. Five-year recurrence-free interval (RFI)/overall survival (OS) was significantly higher in malignant melanoma (81/80%) than in cutaneous Merkel cell carcinoma/HNSCC. Interestingly, 5-year RFI/OS was significantly higher in Merkel cell carcinoma (61%/79%) than in HNSCC (33%/65%; p < .0001) despite comparable TNM classifications and treatment regimens. There were neither differences of RFI/OS between parotid gland Merkel cell carcinoma and parotid gland carcinomas, nor in the immunohistochemical profile. Five-year RFI/OS was significantly better in cutaneous Merkel cell carcinoma when compared with TNM classification matched HNSCC. Five-year RFI/OS was comparable in parotid gland Merkel cell carcinoma and other primary parotid gland malignancies. © 2016 Wiley Periodicals, Inc. Head Neck 39: 92-97, 2017. © 2016 Wiley Periodicals, Inc.

  3. Depsipeptide in Unresectable Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck

    ClinicalTrials.gov

    2015-04-29

    Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Larynx; Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IV Squamous Cell Carcinoma of the Oropharynx

  4. Identification of Prognostic Biomarkers for Progression of Invasive Squamous Cell Carcinoma

    ClinicalTrials.gov

    2017-10-09

    Carcinoma, Squamous Cell; Carcinoma, Squamous; Squamous Cell Carcinoma; Lung Neoplasms; Cancer of Lung; Cancer of the Lung; Lung Cancer; Neoplasms, Lung; Neoplasms, Pulmonary; Pulmonary Cancer; Pulmonary Neoplasms

  5. Merkel Cell Carcinoma Treatment (PDQ®)—Health Professional Version

    Cancer.gov

    Merkel cell carcinoma treatment options include surgery, radiation therapy, and chemotherapy. Get detailed information about the diagnosis and treatment of newly diagnosed and recurrent Merkel cell carcinoma in this summary for clinicians.

  6. Therapeutic challenges in renal cell carcinoma

    PubMed Central

    Penticuff, Justin C; Kyprianou, Natasha

    2015-01-01

    Renal cell carcinoma (RCC) is a malignancy that in advanced disease, is highly resistant to systemic therapies. Elucidation of the angiogenesis pathways and their intrinsic signaling interactions with the genetic and metabolic disturbances within renal cell carcinoma variants has ushered in the era of “targeted therapies”. Advanced surgical interventions and novel drugs targeting VEGF and mTOR, have improved patient survival and prolonged clinically stable-disease states. This review discusses the current understanding of diagnostic challenges and the mechanism-based clinical evidence on therapeutic management of advanced RCC. PMID:26309897

  7. Molecular pathogenesis of ovarian clear cell carcinoma.

    PubMed

    Gounaris, Ioannis; Brenton, James D

    2015-01-01

    Ovarian clear cell carcinoma is a distinct subtype of epithelial ovarian cancer, characterized by an association with endometriosis, glycogen accumulation and resistance to chemotherapy. Key driver events, including ARID1A mutations and HNF1B overexpression, have been recently identified and their functional characterization is ongoing. Additionally, the role of glycogen in promoting the malignant phenotype is coming under scrutiny. Appreciation of the notion that ovarian clear cell carcinoma is essentially an ectopic uterine cancer will hopefully lead to improved animal models of the disease, in turn paving the way for effective treatments.

  8. Histologic Mimics of Basal Cell Carcinoma.

    PubMed

    Stanoszek, Lauren M; Wang, Grace Y; Harms, Paul W

    2017-11-01

    - Basal cell carcinoma (BCC) is the most common human malignant neoplasm and is a frequently encountered diagnosis in dermatopathology. Although BCC may be locally destructive, it rarely metastasizes. Many diagnostic entities display morphologic and immunophenotypic overlap with BCC, including nonneoplastic processes, such as follicular induction over dermatofibroma; benign follicular tumors, such as trichoblastoma, trichoepithelioma, or basaloid follicular hamartoma; and malignant tumors, such as sebaceous carcinoma or Merkel cell carcinoma. Thus, misdiagnosis has significant potential to result in overtreatment or undertreatment. - To review key features distinguishing BCC from histologic mimics, including current evidence regarding immunohistochemical markers useful for that distinction. - Review of pertinent literature on BCC immunohistochemistry and differential diagnosis. - In most cases, BCC can be reliably diagnosed by histopathologic features. Immunohistochemistry may provide useful ancillary data in certain cases. Awareness of potential mimics is critical to avoid misdiagnosis and resulting inappropriate management.

  9. Metastatic Renal Cell Carcinoma to the Pancreas: A Review.

    PubMed

    Cheng, Shaun Kian Hong; Chuah, Khoon Leong

    2016-06-01

    The pancreas is an unusual site for tumor metastasis, accounting for only 2% to 5% of all malignancies affecting the pancreas. The more common metastases affecting the pancreas include renal cell carcinomas, melanomas, colorectal carcinomas, breast carcinomas, and sarcomas. Although pancreatic involvement by nonrenal malignancies indicates widespread systemic disease, metastatic renal cell carcinoma to the pancreas often represents an isolated event and is thus amenable to surgical resection, which is associated with long-term survival. As such, it is important to accurately diagnose pancreatic involvement by metastatic renal cell carcinoma on histology, especially given that renal cell carcinoma metastasis may manifest more than a decade after its initial presentation and diagnosis. In this review, we discuss the clinicopathologic findings of isolated renal cell carcinoma metastases of the pancreas, with special emphasis on separating metastatic renal cell carcinoma and its various differential diagnoses in the pancreas.

  10. Granuloma Inguinale Simulating Squamous Cell Carcinoma.

    PubMed

    Mani, M Z; Singh, Trilochan; Mathew, Mary

    1981-01-01

    A case of extensive granuloma inguinale simulating squamous cell carcinoma is described. There was past history of urethritis leading to a urethral fistula. The ulcer healed almost completely within 19 days of receiving streptomycin injections. The patient had associated scabies and presumably also had latent syphillis (His VDRL was reactive in 1:8 dilution). The patient belonged to Madhya Pradesh.

  11. Perirenal lipoma versus renal cell carcinoma.

    PubMed

    Mydlo, J H; Shore, N; Reuter, V; Herr, H W

    1991-07-01

    Pure renal and perirenal lipomas are rare. They arise from renal cortex, capsule, or perirenal tissue, and may be difficult to distinguish from renal adenocarcinomas. We report on a patient who presented with a renal mass that had the radiologic findings suggestive of a renal cell carcinoma, but proved to be a simple lipoma.

  12. Presumed choroidal metastasis of Merkel cell carcinoma

    SciTech Connect

    Small, K.W.; Rosenwasser, G.O.; Alexander, E. III

    1990-05-01

    Merkel cell carcinoma is a rare skin tumor of neural crest origin and is part of the amine precursor uptake and decarboxylase system. It typically occurs on the face of elderly people. Distant metastasis is almost uniformly fatal. Choroidal metastasis, to our knowledge, has not been described. We report a patient with Merkel cell carcinoma who had a synchronous solid choroidal tumor and a biopsy-proven brain metastasis. Our 56-year-old patient presented with a rapidly growing, violaceous preauricular skin tumor. Computed tomography of the head disclosed incidental brain and choroidal tumors. Light and electron microscopy of biopsy specimens of both themore » skin and the brain lesions showed Merkel cell carcinoma. Ophthalmoscopy, fluorescein angiography, and A and B echography revealed a solid choroidal mass. The brain and skin tumors responded well to irradiation. A radioactive episcleral plaque was applied subsequently to the choroidal tumor. All tumors regressed, and the patient was doing well 28 months later. To our knowledge this is the first case of presumed choroidal metastasis of Merkel cell carcinoma.« less

  13. Clear cell papillary renal cell carcinoma as part of histologically discordant multifocal renal cell carcinoma: A case report and review of literature.

    PubMed

    Shao, Tiffany; Yousef, Peter; Shipilova, Irina; Saleeb, Rola; Lee, Jason Y; Krizova, Adriana

    2016-03-01

    Multifocal renal cell carcinoma of different histological subtypes within a single kidney is rare. We report a recently classified clear cell (tubulo) papillary renal cell carcinoma as part of an unusual case of multifocal renal cell carcinoma of discordant histological subtypes. A 57 year-old-man was found to have multiple renal tumors and cysts on imaging and underwent a laparoscopic left radical nephrectomy. Pathological review showed multifocal renal cell carcinoma (clear cell (tubulo) papillary, clear cell and papillary renal cell carcinomas and papillary adenomas). Morphology of clear cell papillary renal cell carcinoma was supported by immunohistochemical profile (CK7+, HMWK+, CAIX+, AMACR-, CD10-, TFE3-). This is the first report of clear cell papillary renal cell carcinoma as part of multifocal renal cell carcinoma of different histological subtypes. Related lineage of clear cell renal cell carcinoma and papillary renal cell carcinoma is supported by the highest prevalence of their combination within multifocal renal cell carcinoma of different histological subtypes along with their molecular interconnection. Clear cell papillary renal cell carcinoma may be uniquely placed between clear cell and papillary renal cell carcinomas since it shows morphological features intermediate between clear cell and papillary renal cell carcinoma along with overlapping but unique immunohistochemical profile. Clear cell papillary renal cell carcinoma may be molecularly related to clear cell and papillary renal cell carcinomas since the tumors overexpress markers of HIF pathway activation with normal/elevated VHL mRNA expression and some tumors show losses of chromosome 3. Due to the overlapping morphology, it is possible that cases of clear cell papillary renal cell carcinoma may have been misclassified as papillary or clear cell renal cell carcinoma in the literature, incorrectly increasing their reported prevalence. Identification of multifocal RCCs may be related to the

  14. Cutaneous metastasis of bilateral renal cell carcinoma.

    PubMed

    Abbasi, Fariba; Alizadeh, Mansur; Noroozinia, Farahnaz; Moradi, Amin

    2013-01-01

    Renal cell carcinoma (RCC) is a malignant lethal tumour with high potential of metastasis. However, metastasis from RCC to the skin is much less common. It is virtually a sign of poor prognosis. We represent a 42 years old man with bilateral RCC of clear cell type followed by metastasis to the scalp one month later. In this case the relatively young age of the patient, bilaterality of RCC and occurance of skin metastasis in the absence of recurrent kidney tumour are interesting.

  15. Reevaluation and reclassification of resected lung carcinomas originally diagnosed as squamous cell carcinoma using immunohistochemical analysis

    PubMed Central

    Kadota, Kyuichi; Nitadori, Jun-ichi; Rekhtman, Natasha; Jones, David R.; Adusumilli, Prasad S.; Travis, William D.

    2015-01-01

    Currently, non-small cell lung carcinomas are primarily classified by light microscopy. However, recent studies have shown that poorly-differentiated tumors are more accurately classified by immunohistochemistry. In this study, we investigated the use of immunohistochemical analysis in reclassifying lung carcinomas that were originally diagnosed as squamous cell carcinoma. Tumor slides and blocks were available for histologic evaluation, and tissue microarrays were constructed from 480 patients with resected lung carcinomas originally diagnosed as squamous cell carcinoma between 1999 and 2009. Immunohistochemistry for p40, p63, thyroid transcription factor-1 (TTF-1; clone SPT24 and 8G7G3/1), Napsin A, Chromogranin A, Synaptophysin, and CD56 were performed. Staining intensity (weak, moderate, or strong) and distribution (focal or diffuse) were also recorded. Of all, 449 (93.5%) patients were confirmed as having squamous cell carcinomas; the cases were mostly diffusely positive for p40 and negative for TTF-1 (8G7G3/1). Twenty cases (4.2%) were reclassified as adenocarcinoma since they were positive for TTF-1 (8G7G3/1 or SPT24) with either no or focal p40 expression, and all of them were poorly-differentiated with squamoid morphology. In addition, 1 case was reclassified as adenosquamous carcinoma, 4 cases as large cell carcinoma, 4 cases as large cell neuroendocrine carcinoma, and 2 cases as small cell carcinoma. In poorly-differentiated non-small cell lung carcinomas, an accurate distinction between squamous cell carcinoma and adenocarcinoma cannot be reliably determined by morphology alone and requires immunohistochemical analysis, even in resected specimens. Our findings suggest that TTF-1 8G7G3/1 may be better suited as the primary antibody in differentiating adenocarcinoma from squamous cell carcinoma. PMID:25871623

  16. Nevoid Basal Cell Carcinoma Syndrome

    MedlinePlus

    ... develops. Some individuals may have thousands of basal cell cancers in areas of skin that are exposed to ... have been approved to treat people with basal cell cancers that have spread in the body or that ...

  17. Hereditary Papillary Renal Cell Carcinoma

    MedlinePlus

    ... of papillary cancer called type 1 papillary renal cell cancer. Individuals with HPRC have an increased risk of ... that the risk for type 1 papillary renal cell cancer can be passed from generation to generation in ...

  18. Tuft (caveolated) cells in two human colon carcinoma cell lines.

    PubMed

    Barkla, D H; Whitehead, R H; Foster, H; Tutton, P J

    1988-09-01

    The presence of an unusual cell type in two human colon carcinoma cell lines is reported. The cells show the same morphology as "tuft" (caveolated) cells present in normal gastrointestinal epithelium. Tuft cells were seen in cell line LIM 1863 growing in vitro and in human colon carcinoma cell line LIM 2210 growing as subcutaneous solid tumour xenografts in nude mice. Characteristic morphologic features of tuft cells included a wide base, narrow apex and a tuft of long microvilli projecting from the apical surface. The microvilli are attached by a core of long microfilaments passing deep into the apical cytoplasm. Between the microvilli are parallel arrays of vesicles (caveoli) containing flocculent material. Two different but not mutually exclusive explanations for the presence of tuft cells are proposed. The first explanation is that tuft cells came from the resected tumour and have survived by mitotic division during subsequent passages. The second explanation suggests that tuft cells are the progeny of undifferentiated tumour cells. Descriptions of tuft cells in colon carcinomas are uncommon and possible reasons for this are presented. The morphology of tuft cells is consistent with that of a highly differentiated cell specialised for absorption, and these new models provide an opportunity to further investigate the structure and function of tuft cells.

  19. Tuft (caveolated) cells in two human colon carcinoma cell lines.

    PubMed Central

    Barkla, D. H.; Whitehead, R. H.; Foster, H.; Tutton, P. J.

    1988-01-01

    The presence of an unusual cell type in two human colon carcinoma cell lines is reported. The cells show the same morphology as "tuft" (caveolated) cells present in normal gastrointestinal epithelium. Tuft cells were seen in cell line LIM 1863 growing in vitro and in human colon carcinoma cell line LIM 2210 growing as subcutaneous solid tumour xenografts in nude mice. Characteristic morphologic features of tuft cells included a wide base, narrow apex and a tuft of long microvilli projecting from the apical surface. The microvilli are attached by a core of long microfilaments passing deep into the apical cytoplasm. Between the microvilli are parallel arrays of vesicles (caveoli) containing flocculent material. Two different but not mutually exclusive explanations for the presence of tuft cells are proposed. The first explanation is that tuft cells came from the resected tumour and have survived by mitotic division during subsequent passages. The second explanation suggests that tuft cells are the progeny of undifferentiated tumour cells. Descriptions of tuft cells in colon carcinomas are uncommon and possible reasons for this are presented. The morphology of tuft cells is consistent with that of a highly differentiated cell specialised for absorption, and these new models provide an opportunity to further investigate the structure and function of tuft cells. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 PMID:3414781

  20. Chemo-spectroscopic sensor for carboxyl terminus overexpressed in carcinoma cell membrane.

    PubMed

    Stanca, Sarmiza E; Matthäus, Christian; Neugebauer, Ute; Nietzsche, Sandor; Fritzsche, Wolfgang; Dellith, Jan; Heintzmann, Rainer; Weber, Karina; Deckert, Volker; Krafft, Christoph; Popp, Jürgen

    2015-10-01

    Certain carboxyl groups of the plasma membrane are involved in tumorgenesis processes. A gold core-hydroxyapatite shell (AuHA) nanocomposite is introduced as chemo-spectroscopic sensor to monitor these carboxyl groups of the cell membrane. Hydroxyapatite (HA) plays the role both of a chemical detector and of a biocompatible Raman marker. The principle of detection is based on chemical interaction between the hydroxyl groups of the HA and the carboxyl terminus of the proteins. The AuHA exhibits a surface enhanced Raman scattering (SERS) signal at 954 cm(-1) which can be used for its localization. The bio-sensing capacity of AuHA towards human skin epidermoid carcinoma (A431) and Chinese hamster ovary (CHO) cell lines is investigated using Raman microspectroscopic imaging. The localization of AuHA on cells is correlated with scanning electron microscopy, transmission electron microscopy and structured illumination fluorescence microscopy. This qualitative approach is a step towards a quantitative study of the proteins terminus. This method would enable further studies on the molecular profiling of the plasma membrane, in an attempt to provide accurate cell identification. Using a gold core-hydroxyapatite shell (AuHA) nanocomposite, the authors in this paper showed the feasibility of detecting and differentiating cell surface molecules by surface enhanced Raman scattering. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Avelumab Impresses in Merkel Cell Carcinoma.

    PubMed

    2017-06-01

    The PD-L1 inhibitor avelumab-approved by the FDA in March for the treatment of Merkel cell carcinoma-demonstrated a high number of durable responses in an international, open-label, prospective phase II study. The results of the study, which supported the FDA's decision, were presented in April at the American Association for Cancer Research (AACR) Annual Meeting 2017. ©2017 American Association for Cancer Research.

  2. Oral paracoccidioidomycosis or squamous cell carcinoma?

    PubMed

    Kaminagakura, Estela; Graner, Edgard; de Almeida, Oslei Paes; Di Hipolito Júnior, Osvaldo; Lopes, Marcio Ajudarte

    2004-01-01

    Paracoccidioidomycosis is a deep, systemic, and progressive mycosis caused by Paracoccidioides brasiliensis. Oral lesions normally are multiples with a mulberry-like appearance. This article reviews an unusual case involving a chronic, solitary, and ulcerated lesion whose clinical aspects were similar to squamous cell carcinoma. Viewed microscopically, the lesion showed pseudoepitheliomatous hyperplasia and non-necrotizing granulomas. The patient was treated with systemic ketoconazole. Over the next 11 years, follow-up examinations were performed but no recurrence was observed.

  3. The role of mast cells in oral squamous cell carcinoma

    PubMed Central

    Gudiseva, Swetha; Chitturi, Raviteja; Anumula, Vamsikrishna; Poosarla, Chandrashekar; Baddam, Venkat Ramana Reddy

    2017-01-01

    The mast cells are initial effective lineage in both humoral and adaptive immunity. They are ubiquitous in skin, mucosa, and in function. They contain biologically essential and dynamic mediators in healthy and harmful conditions of tissue. Mast cell malfunctioning could be attributed to various chronic allergic diseases. Considerately, emerging evidence of mast cell involvement in various cancers shows them to have both positive and negative roles in tumour growth. It mostly indulges in tumour progression and metastasis via angiogenesis, extracellular matrix degradation, and mitogenic activity in the tumour microenvironment. The current paper reviewed research papers on mast cells in oral squamous cell carcinoma through the PubMed database from 1980 to the present date. The present paper is an attempt to summarise the research reports on the role of mast cells in oral squamous cell carcinoma. Further to this note, this paper also outlines the role of mast cells in normal physiological processes and tumour biology. PMID:28435394

  4. Aggressive squamous cell carcinoma in Kindler syndrome.

    PubMed

    Emanuel, Patrick O; Rudikoff, Donald; Phelps, Robert G

    2006-01-01

    A 57-year-old Hispanic man with a personal and family history of bullae and photosensitivity presented with a fungating, ulcerated squamous cell carcinoma on his left hand (Figure 1). Physical examination showed conjunctival injection, ectropion, symblepharon, urethral stricture, loss of teeth, short stature, and nail dystrophy. There was reticulated erythema, atrophy, hyperpigmentation and hypopigmentation, and telangiectasia of sun-exposed skin of the face, neck, and hands consistent with poikiloderma (Figure 2). In addition, there was foreshortening of the left thumb and sclerodermoid changes of his hands (Figure 3). Radiation therapy was applied to shrink the tumor before a local excision was performed. However, a local recurrence followed and axillary lymph nodes became clinically palpable, necessitating amputation and lymph node dissection. Extensive histologic evaluation of the specimen obtained following left arm amputation and lymph node dissection showed moderate-to-poorly differentiated deeply invasive squamous cell carcinoma. Two of 3 axillary lymph nodes were positive for metastatic carcinoma. A random biopsy of the trunk showed epidermal atrophy, telangiectasia, a perivascular lymphocytic infiltration, and pigment-laden macrophages consistent with poikiloderma. Electron microscopy illustrated extensive reduplication of the basement membrane, with loops, curls, and free extensions of the basal lamina in the superficial dermis; reduced numbers of hemidesmosomes and anchoring fibrils; and a basement membrane focally devoid of basal cells (Figure 4). On the basis of the clinical features and the characteristic basement zone changes, a diagnosis of Kindler syndrome was made.

  5. Localized renal cell carcinoma management: an update.

    PubMed

    Heldwein, Flavio L; McCullough, T Casey; Souto, Carlos A V; Galiano, Marc; Barret, Eric

    2008-01-01

    To review the current modalities of treatment for localized renal cell carcinoma. A literature search for keywords: renal cell carcinoma, radical nephrectomy, nephron sparing surgery, minimally invasive surgery, and cryoablation was performed for the years 2000 through 2008. The most relevant publications were examined. New epidemiologic data and current treatment of renal cancer were covered. Concerning the treatment of clinically localized disease, the literature supports the standardization of partial nephrectomy and laparoscopic approaches as therapeutic options with better functional results and oncologic success comparable to standard radical resection. Promising initial results are now available for minimally invasive therapies, such as cryotherapy and radiofrequency ablation. Active surveillance has been reported with acceptable results, including for those who are poor surgical candidates. This review covers current advances in radical and conservative treatments of localized kidney cancer. The current status of nephron-sparing surgery, ablative therapies, and active surveillance based on natural history has resulted in great progress in the management of localized renal cell carcinoma.

  6. Anogenital squamous cell carcinoma in neglected patient.

    PubMed

    Svecova, D; Havrankova, M; Weismanova, E; Babal, P

    2012-01-01

    Skin squamous cell carcinomas (SCCs) are arguably the second most common carcinoma of the skin and are responsible for the majority of non-melanoma skin cancer deaths. Gynecologist treated a Caucasian 56-years old female patient for genital wart with podophyllotoxin cream. She did not achieve complete response and therefore she has interrupted the therapy and the collaboration with the gynecologist. At the time of evaluation the lesion had a size of man's palm in anogenital region and showed characteristic features of neoplasm. The regional lymph nodes have produced infiltrated painful bubo. PCR analysis for HPV proved negative. Histopathology revealed well-differentiated squamous cell keratinizing carcinoma from the tumor as well as from the regional lymph node packet. Staging computed tomography scans proved negative and pelvis scans disclosed regional lymphadenopathy underlying the tumor. Palliative radiation therapy (by linear accelerator) was administered for the oversized tumor to the total TD 50.0Gy. The patient died 6 months after diagnostic assessment from cardio-respiratory failure. Staging computed tomography before her death did not disclose distinct metastases in her inner organs. Well-differentiated squamous cell keratinizing carcinoma could be growing endophytically affecting the underlying adipose tissue and musculature, with spreading into the regional lymph nodes. The rate of metastases into inner organs seems to vary according to the aggressiveness and metastatic behavior of each SCC. The case report calls for attention to the importance of collaboration among various specialists assisting in the diagnosis and management of skin neoplasm (Fig. 5, Ref. 12). Full Text in PDF www.elis.sk.

  7. Urinary bladder urothelial carcinoma with expression of KIT and PDGFRA and showing diverse differentiations into plasmacytoid, clear cell, acantholytic, nested, and spindle variants, and into adenocarcinoma, signet-ring cell carcinoma, small cell carcinoma, large cell carcinoma, and pleomorphic carcinoma.

    PubMed

    Terada, Tadashi

    2013-01-01

    Various tumors can arise in the urinary bladder (UB); most common is urothelial carcinoma (UC). UC of the UB have many variants. Other types of carcinomas such as adenocarcinoma (AC) and small cell carcinoma (SmCC) can occur in UB carcinomas. Expression of KIT and PDGFRA has not been reported. A 66-year-old man admitted to our hospital because of hematuria. Cystoscopy revealed papillary invasive tumor and a transurethral bladder tumorectomy (TUR-BT) was performed. The TUR-BT showed UC, AC, SmCC, large cell carcinoma (LCC), and pleomorphic carcinoma (PC). The UC component showed plasmacytoid, spindle, nested, clear cell, acantholytic variants. The AC element showed tubular adenocarcinoma and signet-ring cell carcinoma (Sig). Immunohistochemically, all of these subtypes were positive for cytokeratin (CK) AE1/3, CK CAM5.2, CK34BE12, CK5, CK6, CK7, CK8, CK18, CK19, CK20, EMA, CEA, p63, CA19-9, p53 (positive 45%), MUC1, NSE, NCAM, KIT, PDGFRA, and Ki-67 (87%). They were negative for vimentin, chromogranin, synaptophysin, S100 protein, CD34, CD14, α-smooth muscle actin, CD31, caldesmon, CD138, CD45, κ-chain, λ-chain, MUC2, MUC5AC and MUC6. Mucin histochemistry revealed mucins in AC element including Sig. A molecular genetic analysis using PCR-direct sequencing method identified no mutations of KIT (exons 9, 11, 13, and 17) and PDGFRA (exons 12 and 18) genes. The carcinoma was highly aggressive and invaded into muscular layer. The nuclear grade was very high, and there were numerous lymphovascular permeations were seen. The surface showed carcinoma in situ involving von-Brunn's nests. This case shows that carcinoma of UB can show diverse differentiations into numerous histological types and variants, and can express KIT and PDGFRA. The both genes showed no mutations in the present case.

  8. A Study of Varlilumab (Anti-CD27) and Sunitinib in Patients With Metastatic Clear Cell Renal Cell Carcinoma

    ClinicalTrials.gov

    2017-11-10

    Carcinoma, Renal Cell; Kidney Diseases; Kidney Neoplasms; Urogenital Neoplasms; Urologic Diseases; Urologic Neoplasms; Neoplasms; Neoplasms by Histologic Type; Clear-cell Metastatic Renal Cell Carcinoma

  9. Pigmented basal cell carcinoma mimicking a superficial spreading melanoma.

    PubMed

    Hasbún Acuña, Paula; Cullen Aravena, Roberto; Maturana Donaire, César; Ares Mora, Raúl; Porras Kusmanic, Ninoska

    2016-12-20

    Basal cell carcinoma is the most common form of skin cancer, especially in elderly people. Pigmented basal cell carcinoma is a rare subtype and has been described in the literature as a nodular and hyperpigmented lesion; rarely, it can appear as an extensive pigmented plate, which may be clinically indistinguishable from superficial spreading melanoma and Bowen disease. Dermatoscopy has a high sensitivity in the diagnosis of basal cell carcinoma. When Menzies criteria are used; however, the final diagnosis is made by histopathology. The objective of the present report is to analyze the case of a patient with pigmented basal cell carcinoma simulating a superficial spreading melanoma.

  10. Photodynamic Therapy With HPPH in Treating Patients With Squamous Cell Carcinoma of the Oral Cavity

    ClinicalTrials.gov

    2016-04-19

    Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Stage I Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage I Squamous Cell Carcinoma of the Oropharynx; Stage I Verrucous Carcinoma of the Oral Cavity; Stage II Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage II Squamous Cell Carcinoma of the Oropharynx; Stage II Verrucous Carcinoma of the Oral Cavity; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage III Verrucous Carcinoma of the Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVA Verrucous Carcinoma of the Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVB Verrucous Carcinoma of the Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Oropharynx; Stage IVC Verrucous Carcinoma of the Oral Cavity

  11. Mixed primary squamous cell carcinoma, follicular carcinoma, and micropapillary carcinoma of the thyroid gland: A case report.

    PubMed

    Dong, Su; Song, Xue-Song; Chen, Guang; Liu, Jia

    2016-08-01

    Primary squamous cell carcinoma of the thyroid gland is rare, and mixed squamous cell and follicular carcinoma is even rarer still, with only a few cases reported in the literature. The simultaneous presentation of three primary cancers of the thyroid has not been reported previously. Here we report a case of primary squamous cell carcinoma of the thyroid, follicular thyroid carcinoma, and micropapillary thyroid carcinoma. A 62-year-old female patient presented with complaints of pain and a 2-month history of progressively increased swelling in the anterior region of the neck. Fine-needle-aspiration cytology of both lobes indicated the possibility of the presence of a follicular neoplasm. Total thyroidectomy with left-sided modified radical neck dissection was performed. Postoperative pathological examination confirmed the diagnosis of thyroid follicular carcinoma with squamous cell carcinoma and micropapillary carcinoma of the thyroid. Thyroid-stimulating hormone suppressive therapy with l-thyroxine was administered. Radioiodine and radiotherapy also were recommended, but the patient did not complete treatment as scheduled. The patient remained alive more than 9 months after operation. The present case report provides an example of the coexistence of multiple distinct malignancies in the thyroid. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  12. Small cell sweat gland carcinoma of childhood

    PubMed Central

    Drut, R; Giménez, O P; Oliva, J

    2005-01-01

    Small cell sweat gland carcinoma appears to represent a very unusual histological type of sweat gland anlage tumour presenting in children. The differential diagnosis from other small blue cell tumours involving the skin is often difficult. The present report confirms the original observation describing two patients of 2 and 5 years of age harbouring cutaneous tumours. The histology of these lesions showed a monomorphic proliferation of small cells with a high mitotic rate and areas of necrosis. Immunohistochemically, the cells were negative for desmin, cytokeratin 7, cytokeratin 20, Cam 5.2, CD99, chromogranin, CD56, synaptophysin, and S-100, and focally positive for the pancytokeratin marker AE1/AE3, carcinoembryonic antigen (one case), and neurone specific enolase (one case). The prognosis of this type of tumour seems to be good. As more cases are added, the clinical pathological spectrum of the lesion will become better defined. PMID:16311358

  13. Small cell carcinoma of the urinary bladder.

    PubMed

    Terada, Tadashi

    2012-01-01

    Primary small cell carcinoma of the urinary bladder is very rare; only several studies have been reported in the English literature. A 62-year-old woman was admitted to our hospital because of hematuria and dysuria. Bladder endoscopy revealed a large polypoid tumor at the bladder base. Transurethral bladder tumorectomy (TUR-BT) was performed. Many TUR-BT specimens were obtained. Histologically, the bladder tumor was pure small cell carcinoma. Immunohistochemically, the tumor cells were positive for cytokeratin (CK) AE1/3, CK CAM5.2, CK8, CK18, neurone-specific enolase, chromogranin, NCAM (CD56), synaptophysin, Ki-67 (labeling=100%), p53, KIT (CD117), and platelet-derived growth factor receptor-α (PDGFRA). The tumor cells were negative for CK5/6, CK 34BE12, CK7, CK14, CK19, CK20, p63, CD45, and TTF-1. A molecular genetic analysis using PCR-direct sequencing showed no mutations of KIT (exons 9, 11, 13 and 17) and PDGFRA (exons 12 and 18) genes. No metastases were found by various imaging techniques. The patient is now treated by cisplatin-based chemotherapy.

  14. Immunotherapy With MK-3475 in Surgically Resectable Head and Neck Squamous Cell Carcinoma

    ClinicalTrials.gov

    2018-02-08

    Cancer of Head and Neck; Head and Neck Cancer; Neoplasms, Head and Neck; Carcinoma, Squamous Cell of Head and Neck; Squamous Cell Carcinoma of the Head and Neck; Squamous Cell Carcinoma, Head and Neck

  15. 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.

  16. [Descriptive study on basal cell eyelid carcinoma].

    PubMed

    Pfeiffer, M J; Pfeiffer, N; Valor, C

    2015-09-01

    To describe a series of cases of basal cell carcinomas of the eyelid. A descriptive and retrospective study was conducted by reviewing the medical outcome, histopathological history, and photographic images of 200 patients with basal cell eyelid carcinomas. All were treated in the Herzog Carl Theodor Eye Hospital in Munich, Germany, between 2000 and 2013. In the present study, it was found that females are more affected than males. The mean age of presentation of the tumor occurred at the age of 70 years. In 50% of the cases the tumor was found on the lower lid, especially medially from the center of the lid. The lid margin was involved in 47% of all tumors. The mean diameter was 9.2mm. The recurrence rate after surgery with histologically clear resection margins was 5%. There was a significant relationship between tumor diameter and age. As tumors where located farther away from medial and closer to the lid margin, they became larger. There is a predominance of women affected by this tumor. This may be related to the fact that the sample was taken from those attending an oculoplastic surgery clinic, where there are generally more women than men attending. The formation of basal cell carcinomas increases with age. The infrequent involvement of the upper lid could be explained by the protection of the the eyebrow. The frequent involvement of the lower lid may be due to the light reflection (total reflection) by the cornea on the lower lid margin. Also chemical and physical effects of the tears may be more harmful on the lower lid. Patients tend to ask for medical help when they are females, younger, when the tumor is closer to the medial canthus or when the tumor is away from the lid margin. Copyright © 2014 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

  17. Therapeutic vaccines in renal cell carcinoma.

    PubMed

    Schwaab, Thomas; Ernstoff, Marc S

    2011-07-01

    Metastatic renal cell carcinoma (mRCC) is a lethal disease. The advent of tyrosine kinase inhibitors (TKIs) has changed the disease process, yet the majority of patients will develop treatment-resistant disease. IL-2 based immunotherapy in mRCC is the only US FDA-approved treatment with curative results. Immunotherapeutic vaccine approaches to mRCC have been under investigation for several decades with mixed results. The recent FDA-approval of the first cellular immunotherapy in prostate cancer (Provenge(®)) has reinvigorated the search for similar vaccines approaches in mRCC. This review introduces the concepts and different features required for a successful anticancer vaccine approach.

  18. Merkel cell polyomavirus infection and Merkel cell carcinoma.

    PubMed

    Liu, Wei; MacDonald, Margo; You, Jianxin

    2016-10-01

    Merkel cell polyomavirus is the only polyomavirus discovered to date that is associated with a human cancer. MCPyV infection is highly prevalent in the general population. Nearly all healthy adults asymptomatically shed MCPyV from their skin. However, in elderly and immunosuppressed individuals, the infection can lead to a lethal form of skin cancer, Merkel cell carcinoma. In the last few years, new findings have established links between MCPyV infection, host immune response, and Merkel cell carcinoma development. This review discusses these recent discoveries on how MCPyV interacts with host cells to achieve persistent infection and, in the immunocompromised population, contributes to MCC development. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Airway Basal Cell Heterogeneity and Lung Squamous Cell Carcinoma.

    PubMed

    Hynds, Robert E; Janes, Sam M

    2017-09-01

    Basal cells are stem/progenitor cells that maintain airway homeostasis, enact repair following epithelial injury, and are a candidate cell-of-origin for lung squamous cell carcinoma. Heterogeneity of basal cells is recognized in terms of gene expression and differentiation capacity. In this Issue, Pagano and colleagues isolate a subset of immortalized basal cells that are characterized by high motility, suggesting that they might also be heterogeneous in their biophysical properties. Motility-selected cells displayed an increased ability to colonize the lung in vivo The possible implications of these findings are discussed in terms of basal cell heterogeneity, epithelial cell migration, and modeling of metastasis that occurs early in cancer evolution. Cancer Prev Res; 10(9); 491-3. ©2017 AACR See related article by Pagano et al., p. 514 . ©2017 American Association for Cancer Research.

  20. Pulmonary giant cell carcinoma associated with pseudomyxoma peritonei.

    PubMed

    Goldin, Mark; Li, Jinghong; Amirrezvani, Ali; Riker, David

    2012-01-01

    Pulmonary giant cell carcinoma is a rare subtype of sarcomatoid carcinoma. Pseudomyxoma peritonei (PMP) is a rare condition in which gelatinous material accumulates within the peritoneal cavity. It is believed PMP arises from a primary appendiceal mucinous neoplasm that perforates the gut, causing mucinous ascites. There are sporadic reports of PMP associated with neoplasms of other organs, rarely the lung. Here, we report on a 60-year-old woman with pulmonary giant cell carcinoma associated with PMP. She presented with progressive dyspnea and abdominal distention. Abdominal computed tomography revealed moderately dense ascites without an obvious mass. Chest computed tomography revealed a large, solitary right lower-lobe lung mass. She underwent transbronchial fine-needle aspiration of the mass, and was diagnosed with pulmonary giant cell carcinoma. The ascites showed scattered malignant cells in a background of mucin, confirming PMP. To our knowledge, this is the first report of pulmonary giant cell carcinoma associated with PMP.

  1. Targeting HIF2 in Clear Cell Renal Cell Carcinoma.

    PubMed

    Cho, Hyejin; Kaelin, William G

    2016-01-01

    Inactivation of the von Hippel-Lindau tumor-suppressor protein (pVHL) is the signature "truncal" event in clear cell renal cell carcinoma, which is the most common form of kidney cancer. pVHL is part of a ubiquitin ligase the targets the α subunit of the hypoxia-inducible factor (HIF) transcription factor for destruction when oxygen is available. Preclinical studies strongly suggest that deregulation of HIF, and particularly HIF2, drives pVHL-defective renal carcinogenesis. Although HIF2α was classically considered undruggable, structural and chemical work by Rick Bruick and Kevin Gardner at University of Texas Southwestern laid the foundation for the development of small molecule direct HIF2α antagonists (PT2385 and the related tool compound PT2399) by Peloton Therapeutics that block the dimerization of HIF2α with its partner protein ARNT1. These compounds inhibit clear cell renal cell carcinoma growth in preclinical models, and PT2385 has now entered the clinic. Nonetheless, the availability of such compounds, together with clustered regularly interspaced short palindromic repeat (CRISPR)-based gene editing approaches, has revealed a previously unappreciated heterogeneity among clear cell renal carcinomas and patient-derived xenografts with respect to HIF2 dependence, suggesting that predictive biomarkers will be needed to optimize the use of such agents in the clinic. © 2016 Cho and Kaelin; Published by Cold Spring Harbor Laboratory Press.

  2. Targeting Btk with ibrutinib inhibit gastric carcinoma cells growth.

    PubMed

    Wang, Jin Dao; Chen, Xiao Ying; Ji, Ke Wei; Tao, Feng

    2016-01-01

    Bruton's tyrosine kinase (Btk) is a member of the Tec-family non-receptor tyrosine kinases family. It has previously been reported to be expressed in B cells and has an important role in B-cell malignancies. While the roles of Btk in the pathogenesis of certain B-cell malignancies are well established, the functions of Btk in gastric carcinoma have never been investigated. Herein, we found that Btk is over-expressed in gastric carcinoma tissues and gastric cancer cells. Knockdown of Btk expression selectively inhibits the growth of gastric cancer cells, but not that of the normal gastric mucosa epithelial cell, which express very little Btk. Inhibition of Btk by its inhibitor ibrutinib has an additive inhibitory effect on gastric cancer cell growth. Treatment of gastric cancer cells, but not immortalized breast epithelial cells with ibrutinib results in effective cell killing, accompanied by the attenuation of Btk signals. Ibrutinib also induces apoptosis in gastric carcinoma cells as well as is a chemo-sensitizer for docetaxel (DTX), a standard of care for gastric carcinoma patients. Finally, ibrutinib markedly reduces tumor growth and increases tumor cell apoptosis in the tumors formed in mice inoculated with the gastric carcinoma cells. Given these promising preclinical results for ibrutinib in gastric carcinoma, a strategy combining Btk inhibitor warrants attention in gastric cancer.

  3. Targeting Btk with ibrutinib inhibit gastric carcinoma cells growth

    PubMed Central

    Wang, Jin Dao; Chen, Xiao Ying; Ji, Ke Wei; Tao, Feng

    2016-01-01

    Bruton’s tyrosine kinase (Btk) is a member of the Tec-family non-receptor tyrosine kinases family. It has previously been reported to be expressed in B cells and has an important role in B-cell malignancies. While the roles of Btk in the pathogenesis of certain B-cell malignancies are well established, the functions of Btk in gastric carcinoma have never been investigated. Herein, we found that Btk is over-expressed in gastric carcinoma tissues and gastric cancer cells. Knockdown of Btk expression selectively inhibits the growth of gastric cancer cells, but not that of the normal gastric mucosa epithelial cell, which express very little Btk. Inhibition of Btk by its inhibitor ibrutinib has an additive inhibitory effect on gastric cancer cell growth. Treatment of gastric cancer cells, but not immortalized breast epithelial cells with ibrutinib results in effective cell killing, accompanied by the attenuation of Btk signals. Ibrutinib also induces apoptosis in gastric carcinoma cells as well as is a chemo-sensitizer for docetaxel (DTX), a standard of care for gastric carcinoma patients. Finally, ibrutinib markedly reduces tumor growth and increases tumor cell apoptosis in the tumors formed in mice inoculated with the gastric carcinoma cells. Given these promising preclinical results for ibrutinib in gastric carcinoma, a strategy combining Btk inhibitor warrants attention in gastric cancer. PMID:27508020

  4. Pembrolizumab Combined With Cetuximab for Treatment of Recurrent/Metastatic Head & Neck Squamous Cell Carcinoma

    ClinicalTrials.gov

    2018-05-21

    HNSCC; Lip SCC; Oral Cavity Cancer; Oropharynx Cancer; Larynx Cancer; Hypopharynx Cancer; Nasopharynx Cancer; Sinonasal Carcinoma; Cutaneous Squamous Cell Carcinoma; Head and Neck Neoplasms; Head and Neck Cancer; Head and Neck Squamous Cell Carcinoma

  5. Purification and characterization of a membrane-associated 3,3',5-triiodo-L-thyronine binding protein from a human carcinoma cell line.

    PubMed Central

    Cheng, S Y; Hasumura, S; Willingham, M C; Pastan, I

    1986-01-01

    A membrane-associated binding protein for 3,3',5-triiodo-L-thyronine (T3) was purified to apparent homogeneity from A431 human epidermoid carcinoma cells. A431 cells were specifically labeled with the N-bromoacetyl derivative of T3 labeled with 125I at the 3' position (BrAc[125I]T3) and were extracted with 3-[3-(cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS), a zwitterionic detergent. The solubilized BrAc[125I]T3-labeled protein was successively purified by chromatography on Sephadex G-200 and QAE-Sephadex followed by NaDod-SO4/PAGE. Approximately 0.2 mg of purified protein was obtained from 2.5 X 10(9) cells, which represents a 3000-fold purification. The membrane-associated T3 binding protein is an acidic protein with a pI of 5.1 and an apparent molecular mass of 55,000 daltons determined by NaDodSO4/PAGE. Polyclonal antibodies against the 55-kDa protein were prepared and used in indirect immunofluorescence to show that the 55-kDa protein was mainly found in the nuclear envelope and endoplasmic reticulum. Images PMID:3006034

  6. Red Dot Basal Cell Carcinoma: Report of Cases and Review of This Unique Presentation of Basal Cell Carcinoma.

    PubMed

    Cohen, Philip R

    2017-03-22

    Red dot basal cell carcinoma is a unique variant of basal cell carcinoma. Including the three patients described in this report, red dot basal cell carcinoma has only been described in seven individuals. This paper describes the features of two males and one female with red dot basal cell carcinoma and reviews the characteristics of other patients with this clinical subtype of basal cell carcinoma. A 70-year-old male developed a pearly-colored papule with a red dot in the center on his nasal tip. A 71-year-old male developed a red dot surrounded by a flesh-colored papule on his left nostril. Lastly, a 74-year-old female developed a red dot within an area of erythema on her left mid back. Biopsy of the lesions all showed nodular and/or superficial basal cell carcinoma. Correlation of the clinical presentation and pathology established the diagnosis of red dot basal cell carcinoma. The tumors were treated by excision using the Mohs surgical technique. Pubmed was searched with the keyword: basal, cell, cancer, carcinoma, dot, red, and skin. The papers generated by the search and their references were reviewed. Red dot basal cell carcinoma has been described in three females and two males; the gender was not reported in two patients. The tumor was located on the nose (five patients), back (one patient) and thigh (one patient). Cancer presented as a solitary small red macule or papule; often, the carcinoma was surrounded by erythema or a flesh-colored papule. Although basal cell carcinomas usually do not blanch after a glass microscope slide is pressed against them, the red dot basal cell carcinoma blanched after diascopy in two of the patients, resulting in a delay of diagnosis in one of these individuals. Dermoscopy may be a useful non-invasive modality for evaluating skin lesions when the diagnosis of red dot basal cell carcinoma is considered. Mohs surgery is the treatment of choice; in some of the patients, the ratio of the area of the postoperative wound to that

  7. Red Dot Basal Cell Carcinoma: Report of Cases and Review of This Unique Presentation of Basal Cell Carcinoma

    PubMed Central

    2017-01-01

    Red dot basal cell carcinoma is a unique variant of basal cell carcinoma. Including the three patients described in this report, red dot basal cell carcinoma has only been described in seven individuals. This paper describes the features of two males and one female with red dot basal cell carcinoma and reviews the characteristics of other patients with this clinical subtype of basal cell carcinoma. A 70-year-old male developed a pearly-colored papule with a red dot in the center on his nasal tip. A 71-year-old male developed a red dot surrounded by a flesh-colored papule on his left nostril. Lastly, a 74-year-old female developed a red dot within an area of erythema on her left mid back. Biopsy of the lesions all showed nodular and/or superficial basal cell carcinoma. Correlation of the clinical presentation and pathology established the diagnosis of red dot basal cell carcinoma. The tumors were treated by excision using the Mohs surgical technique. Pubmed was searched with the keyword: basal, cell, cancer, carcinoma, dot, red, and skin. The papers generated by the search and their references were reviewed. Red dot basal cell carcinoma has been described in three females and two males; the gender was not reported in two patients. The tumor was located on the nose (five patients), back (one patient) and thigh (one patient). Cancer presented as a solitary small red macule or papule; often, the carcinoma was surrounded by erythema or a flesh-colored papule. Although basal cell carcinomas usually do not blanch after a glass microscope slide is pressed against them, the red dot basal cell carcinoma blanched after diascopy in two of the patients, resulting in a delay of diagnosis in one of these individuals. Dermoscopy may be a useful non-invasive modality for evaluating skin lesions when the diagnosis of red dot basal cell carcinoma is considered. Mohs surgery is the treatment of choice; in some of the patients, the ratio of the area of the postoperative wound to that

  8. Diagnostic utility of hepatocyte nuclear factor 1-beta immunoreactivity in endometrial carcinomas: lack of specificity for endometrial clear cell carcinoma.

    PubMed

    Fadare, Oluwole; Liang, Sharon X

    2012-12-01

    Hepatocyte nuclear factor 1-beta (HNF1β) has recently emerged as a relatively sensitive and specific marker for ovarian clear cell carcinoma. The purpose of this study is to assess the diagnostic utility of this marker for endometrial clear cell carcinoma. Immunohistochemical analysis was performed on 75 endometrial tissues using a goat polyclonal antibody raised against a peptide mapping at the C-terminus of human HNF1β protein. The 75 cases included 15 clear cell carcinomas, 20 endometrioid carcinomas, 15 endometrial serous carcinomas/uterine papillary serous carcinomas, 20 cases of normal endometrium, 2 cases of clear cell metaplasia, and 3 cases of Arias Stella reaction. Staining interpretations were based on a semiquantitative scoring system, a 0 to 12+ continuous numerical scale that was derived by multiplying the extent of staining (0 to 4+ scale) by the intensity of staining (0 to 3+ scale) for each case. HNF1β expression was found to be present in a wide spectrum of tissues. Twenty-seven (54%) of the 50 carcinomas displayed at least focal nuclear HNF1β expression, including 11 (73%) of 15, 9 (60%) of 15, and 7 (35%) of 20 clear cell, serous, and endometrioid carcinomas, respectively. The average nuclear staining scores for clear cell carcinomas, endometrioid carcinomas, and serous carcinomas were 5.2, 1.4, and 4.1, respectively. Clear cell carcinomas and endometrioid carcinomas displayed statistically significant differences regarding their nuclear staining scores (P = 0.0027), but clear cell carcinomas and endometrial serous carcinomas did not (P = 0.45). The calculated sensitivity of any nuclear HNF1β expression in classifying a carcinoma as being of the clear cell histotype was 73%, whereas the specificity was 54%. Nineteen of 20 normal endometrium samples displayed at least focal nuclear expression of HNF1β, and this expression was often diffuse. The 5 cases of benign histologic mimics of clear cell carcinomas (Arias Stella reaction and clear

  9. Metastatic squamous cell carcinoma thyroid from functionally cured cancer cervix

    PubMed Central

    Vamsy, Mohana; Dattatreya, Palanki Satya; Sarma, Lella Yugandhar; Dayal, Monal; Janardhan, Nandigam; Rao, Vatturi Venkata Satya Prabhakar

    2013-01-01

    The authors report a very unusual occurrence of a metastatic squamous carcinoma to thyroid gland from a treated squamous cell carcinoma cervix 12 years before with no recurrence at the primary site. The case also has an additional complexity of rapid progression of the metastatic thyroid carcinoma to wide spread dissemination to lungs and bones while on concurrent chemo radio therapy confirming the aggressiveness of the entity. PMID:24163519

  10. Merkel Cell Carcinoma Metastatic to Pleural Fluid: A Case Report.

    PubMed

    Rhee, Ye-Young; Kim, Soo Hee; Kim, Eun Kyung; Kim, Se Hoon

    2018-05-01

    Merkel cell carcinoma (MCC) is a rare aggressive neuroendocrine carcinoma of the skin that shows locoregional or distant metastasis. Metastasis of MCC to body cavity effusion is extremely rare; only three cases have been reported so far. Metastatic MCC in effusion cytology shows small blue round cells with fine stippled chromatin like other small blue round cell tumors such as small cell lung carcinoma or lymphoma. The diagnosis of metastatic MCC can grant patients good chances at recently advanced therapeutic options. Here, we present a case of metastatic MCC to pleural effusion with characteristic single file-like pattern.

  11. Presentation of renal cell carcinoma as cervical polyp metastasis.

    PubMed

    Godfrey, Gwendolyn J; Moore, Grace; Alatassi, Houda

    2010-10-01

    Secondary cervical adenocarcinomas are most commonly seen owing to the extension of a primary endometrial adenocarcinoma. Metastatic tumors from other sites are rather uncommon and, when seen, are most frequently from the ovaries, gastrointestinal tract, or breast. We report a case of metastatic renal cell carcinoma, clear cell variant, to the cervix, which presented as a cervical polyp in a postmenopausal female. To our knowledge, this is the fourth reported case of renal cell carcinoma metastatic to the cervix. This case is only the third in which the cervical metastasis was the presenting sign of renal cell carcinoma and the first in which the clinical presentation was as a cervical polyp.

  12. Origin of clear cell carcinoma: nature or nurture?

    PubMed

    Kolin, David L; Dinulescu, Daniela M; Crum, Christopher P

    2018-02-01

    A rare but serious complication of endometriosis is the development of carcinoma, and clear cell and endometrioid carcinomas of the ovary are the two most common malignancies which arise from endometriosis. They are distinct diseases, characterized by unique morphologies, immunohistochemical profiles, and responses to treatment. However, both arise in endometriosis and can share common mutations. The overlapping mutational profiles of clear cell and endometrioid carcinomas suggest that their varied histologies may be due to a different cell of origin which gives rise to each type of cancer. Cochrane and colleagues address this question in a recent article in this journal. They show that a marker of ovarian clear cell carcinoma, cystathionine gamma lyase, is expressed in ciliated cells. Similarly, they show that markers of secretory cells (estrogen receptor and methylenetetrahydrofolate dehydrogenase 1) are expressed in ovarian endometrioid carcinoma. Taken together, they suggest that endometrioid and clear cell carcinomas arise from cells related to secretory and ciliated cells, respectively. We discuss Cochrane et al's work in the context of other efforts to determine the cell of origin of gynecological malignancies, with an emphasis on recent developments and challenges unique to the area. These limitations complicate our interpretation of tumor differentiation; does it reflect nature imposed by a specific cell of origin or nurture, by either mutation(s) or environment? Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  13. Radiation Therapy With or Without Cisplatin in Treating Patients With Stage III-IV Squamous Cell Carcinoma of the Head and Neck Who Have Undergone Surgery

    ClinicalTrials.gov

    2017-12-07

    Head and Neck Squamous Cell Carcinoma; Laryngeal Squamous Cell Carcinoma, Spindle Cell Variant; Stage III Hypopharyngeal Squamous Cell Carcinoma; Stage III Laryngeal Squamous Cell Carcinoma; Stage III Laryngeal Verrucous Carcinoma; Stage III Oral Cavity Squamous Cell Carcinoma; Stage III Oral Cavity Verrucous Carcinoma; Stage III Oropharyngeal Squamous Cell Carcinoma; Stage IVA Hypopharyngeal Squamous Cell Carcinoma; Stage IVA Laryngeal Squamous Cell Carcinoma; Stage IVA Laryngeal Verrucous Carcinoma; Stage IVA Oral Cavity Squamous Cell Carcinoma; Stage IVA Oral Cavity Verrucous Carcinoma; Stage IVA Oropharyngeal Squamous Cell Carcinoma

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

    SciTech Connect

    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

  15. Neuroendocrine differentiation in basal cell carcinoma.

    PubMed

    Houcine, Yoldez; Chelly, Ines; Zehani, Alia; Belhaj Kacem, Linda; Azzouz, Haifa; Rekik, Wafa; C, Hend; Haouet, Slim; Kchir, Nidhameddine

    2017-01-01

    Basal cell carcinoma (BCC) is the prototypical basaloid tumor of the skin. It may show various patterns simulating other cutaneous tumors due to its pleomorphism. It may have an unusal pattern of differentiation such as squamous, sebaceous, apocrine, eccrine, pilar, and endocrine differentiation. In order to establish the relative frequency of neuroendocrine differentiation in BCC, we performed a retrospective study of 33 consecutive BCCs using conventional immunohistochemistry with two neuroendocrine antibodies: Chromogranine A and synaptophysine. The age of the patients ranged from 17-83 years with mean of 65 years. The male to female ratio was 16:17. In immunohistochimestry, Chromogranine A was seen in 72.2% (24/33) while Synaptophysine was positive in 9.09% (3/33). Their expression was cytoplasmic and membranous and was seen in the periphery of these tumors in the overlying cells. Positive staining of chromogranine A was high (75-100% of tumors cells) in 9%, intermediate (25-75% of tumors cells) in 33% of cases and relatively low (<25%) in 30.3% of cases.

  16. Basal Cell Carcinoma Arising within Seborrheic Keratosis

    PubMed Central

    Yurdakul, Cüneyt; Güçer, Hasan; Sehitoglu, Ibrahim

    2014-01-01

    Malignant tumour development within a seborrheic keratosis (SK) is extremely rare. Though the most commonly developed malignant tumour is the basal cell carcinoma (BCC), other tumour types have also been reported in literature. Herein, we will report a superficial type BCC case developed within SK localized in hairy skin of a 78-year-old female patient. In immunohistochemical evaluation, diffuse positive staining with CK19 and over-expression in p53 compared with non-neoplastic areas were determined in neoplastic basaloid islands. It is always not easy to differentiate especially superficial type BCC cases from non-neoplastic epithelium of SK with histopathological evaluation. As far as this reason we believe that in difficult differentiation of these 2 lesions, in order to show the differentiation in basal epithelium, immunohistochemical evaluation may be helpful. PMID:25177624

  17. [Muscular metastases from renal cell carcinoma].

    PubMed

    Montagnac, Richard; Champion, Justine; Pradel, Jean; Takin, Romulus; Eychenne, Dominique; Schendel, Adeline

    2016-12-01

    Renal cell carcinoma can metastasize to several locations but rarely in muscles. However, this possibility must never be overlooked because muscle metastases may occur a very long time after the initial nephrectomy. So the post-operative follow-up, according to the recommendations, with thoraco-abdomino-pelvic imaging (computed tomography or nuclear magnetic resonance) allowing to detect metastases, including muscle metastases in the trunk, does not have to neglect the metastases located in the members. This search is based upon a thorough clinical examination, completed by targeted imaging in case of symptoms and/or palpable mass. Copyright © 2016 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.

  18. Subungual squamous cell carcinoma: A case study

    SciTech Connect

    Neill, Cory J., E-mail: coryjneill@gmail.com

    The purpose of this case study is to describe a dosimetric delivery of radiation to a superficial disease process involving the skin and bone of the distal finger. A 76-year-old male patient presented with a subungual squamous cell carcinoma (SCC) of the left distal index finger with bony involvement. The patient refused conventional surgical treatment but agreed to external beam radiation therapy (EBRT). There is a gap in the current literature describing how to successfully immobilize fingers and which EBRT modality is dosimetrically advantageous in treating them. The construction of a simple immobilization method with the patient in a reproduciblemore » position is described. The use of photons and electrons were compared ultimately showing photons to be dosimetrically advantageous. Long-term efficacy of the treatment was not evaluated because of patient noncompliance.« less

  19. Circular RNA expression in basal cell carcinoma.

    PubMed

    Sand, Michael; Bechara, Falk G; Sand, Daniel; Gambichler, Thilo; Hahn, Stephan A; Bromba, Michael; Stockfleth, Eggert; Hessam, Schapoor

    2016-05-01

    Circular RNAs (circRNAs), are nonprotein coding RNAs consisting of a circular loop with multiple miRNA, binding sites called miRNA response elements (MREs), functioning as miRNA sponges. This study was performed to identify differentially expressed circRNAs and their MREs in basal cell carcinoma (BCC). Microarray circRNA expression profiles were acquired from BCC and control followed by qRT-PCR validation. Bioinformatical target prediction revealed multiple MREs. Sequence analysis was performed concerning MRE interaction potential with the BCC miRNome. We identified 23 upregulated and 48 downregulated circRNAs with 354 miRNA response elements capable of sequestering miRNA target sequences of the BCC miRNome. The present study describes a variety of circRNAs that are potentially involved in the molecular pathogenesis of BCC.

  20. Merkel cell carcinoma with seborrheic keratosis: A unique association.

    PubMed

    Anand, Murthy S; Krishnamurthy, Shantha; Ravindranath, Suvarna; Ranganathan, Jyothi

    2018-01-01

    Merkel cell carcinoma (MCC) is a rare, clinically aggressive neuroendocrine carcinoma of the skin; MCC is 40 times less common as compared to melanoma. The most frequently reported sites have been the head and neck, extremities, and trunk. Potential mimics include malignant melanoma, lymphoma, or metastatic small cell (neuroendocrine) carcinomas. Histopathology of MCC resembles small cell carcinoma both morphologically and on IHC. The possible cell of origin was proposed as the Merkel cell, which functions as a mechanoreceptor. It has a high chance of local recurrence, regional and distant spread. In recent times, Merkel cell polyomavirus has been implicated as the causative agent for this tumor. The same agent has a reported etiologic association with other skin lesions, including seborrheic keratosis.

  1. 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.

  2. Effects of Cabazitaxel in Renal Cell Carcinoma Cell Lines.

    PubMed

    Mizutani, Kosuke; Tomoda, Masashi; Ohno, Yuta; Hayashi, Hideki; Fujita, Yasunori; Kawakami, Kyojiro; Kameyama, Koji; Kato, Taku; Sugiyama, Tadashi; Itoh, Yoshinori; Ito, Masafumi; Deguchi, Takashi

    2015-12-01

    Advanced renal cell carcinoma is treated with mammalian target of rapamycin (mTOR) inhibitors or tyrosine kinase inhibitors (TKIs). The effects of these drugs are, however, limited and novel treatment strategies are required. Clear-cell type renal cell carcinoma (ccRCC) is chemo-resistant, in part, due to expression of multidrug resistance proteins such as p-glycoprotein. Cabazitaxel, a tubulin-binding taxane drug used for castration-resistant prostate cancer, has less affinity for p-glycoprotein compared to docetaxel. In the current study, the effects of docetaxel and cabazitaxel on ccRCC cells were investigated. The expression of p-glycoprotein was evaluated in the ccRCC cell lines, Caki-1, KMRC-1 and OS-RC-2 by western blotting. Cells were treated with cabazitaxel or docetaxel, and growth kinetics and tubulin polymerization were determined by the WST-1 assay and cell-based tubulin polymerization assay, respectively. Intracellular drug concentrations were measured by chromatography. AKT activation after treatment was examined by western blotting. All ccRCC cell lines expressed p-glycoprotein. Cabazitaxel inhibited cell growth and induced tubulin polymerization more potently than docetaxel. The intracellular concentration of cabazitaxel was much higher than docetaxel in all cell lines. Both docetaxel and cabazitaxel inhibit AKT phosphorylation at 5 min among three cells. Cabazitaxel inhibits growth of ccRCC cells expressing p-glycoprotein and could thus be possibly used for advanced ccRCC patients in combination with targeted-therapy enhancing their effects. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  3. Squamous cell carcinoma of the anal sacs in three dogs.

    PubMed

    Mellett, S; Verganti, S; Murphy, S; Bowlt, K

    2015-03-01

    Anal sac squamous cell carcinoma is rare in dogs. Five cases have been previously reported, treatment of which involved surgery alone. This report describes three further cases of canine anal sac squamous cell carcinoma which underwent medical (meloxicam) management alone, resulting in survival of up to seven months. No metastases were identified. Squamous cell carcinoma, although extremely uncommon, should be considered as a possible differential diagnosis when a dog is presented for investigation of an anal sac mass. © 2014 British Small Animal Veterinary Association.

  4. Diabetes and Risk of Renal Cell Carcinoma

    PubMed Central

    Habib, Samy L; Prihoda, Thomas J; Luna, Maria; Werner, Sherry A

    2012-01-01

    Background and objectives: There is evidence that the incidence of solid tumors is markedly increased in patients with diabetes mellitus. In the current study, we investigate the association between diabetes and renal cancer. Patients and Methods: A single-center retrospective analysis of 473 patients who underwent nephrectomy for renal cell carcinoma (RCC) was performed. Diabetic RCC patients were screened for age, gender, ethnicity, HgA1C, glucose levels and renal function. Results: Of the 473 cases with RCC, we identified 120 patients (25.4%) with a history of diabetes. The incidence of diabetes in RCC patients was higher in female than male subjects and in Hispanic compared to White and Other ethnic backgrounds. At diagnosis, the majority of diabetic RCC patients were 50-59 years of age. In diabetic RCC cases, clear cell type histology (92.0%), nuclear grade 2 (56.1%) and tumor size range from 1-5 cm (65.7%) were the most common in each category. Conclusion: Our findings indicate that diabetic RCC patients have a predominance of localized, small clear cell RCC. In addition, females with a history of RCC have a higher frequency of diabetes compared to males. This is the first report of clinical and histopathological features of RCC associated with diabetes. PMID:22232697

  5. Identification of Human Cutaneous Basal Cell Carcinoma Cancer Stem Cells.

    PubMed

    Morgan, Huw; Olivero, Carlotta; Patel, Girish K

    2018-04-20

    The cancer stem cell model states that a subset of tumor cells, called "cancer stem cells," can initiate and propagate tumor growth through self-renewal, high proliferative capacity, and their ability to recreate tumor heterogeneity. In basal cell carcinoma (BCC), we have shown that tumor cells that express the cell surface protein CD200 fulfill the cancer stem cell hypothesis. CD200+ CD45- BCC cells represent 0.05-3.96% of all BCC cells and reside in small clusters at the tumor periphery. Using a novel, reproducible in vivo xenograft growth assay, we determined that tumor-initiating cell (TIC) frequencies are approximately 1 per 1.5 million unsorted BCC cells. The CD200+ CD45- BCC subpopulation recreated BCC tumor growth in vivo with typical histological architecture and expression of sonic hedgehog-regulated genes. Reproducible in vivo BCC growth was achieved with as few as 10,000 CD200+ CD45- cells, representing ~1500-fold enrichment. The methods used to identify and purify CD200+ CD45- BCC cells, as well as characterize gene expression, are described herein.

  6. Detection of squamous carcinoma cells using gold nanoparticles

    NASA Astrophysics Data System (ADS)

    Dai, Wei-Yun; Lee, Sze-tsen; Hsu, Yih-Chih

    2015-03-01

    The goal of this study is to use gold nanoparticle as a diagnostic agent to detect human squamous carcinoma cells. Gold nanoparticles were synthesized and the gold nanoparticle size was 34.3 ± 6.2 nm. Based on the over-expression of epidermal growth factor receptor (EGFR) biomarkers in squamous carcinoma cells, we hypothesized that EGFR could be a feasible biomarker with a target moiety for detection. We further modified polyclonal antibodies of EGFR on the surface of gold nanoparticles. We found selected squamous carcinoma cells can be selectively detected using EGFR antibody-modified gold nanoparticles via receptor-mediated endocytosis. Cell death was also examined to determine the survival status of squamous carcinoma cells with respect to gold nanoparticle treatment and EGFR polyclonal antibody modification.

  7. Radiation sensitivity of Merkel cell carcinoma cell lines

    SciTech Connect

    Leonard, J.H.; Ramsay, J.R.; Birrell, G.W.

    1995-07-30

    Merkel cell carcinoma (MCC), being a small cell carcinoma, would be expected to be sensitive to radiation. Clinical analysis of patients at our center, especially those with macroscopic disease, would suggest the response is quite variable. We have recently established a number of MCC cell lines from patients prior to radiotherapy, and for the first time are in a position to determine their sensitivity under controlled conditions. Some of the MCC lines grew as suspension cultures and could not be single cell cloned; therefore, it was not possible to use clonogenic survival for all cell lines. A tetrazolium based (MTT)more » assay was used for these lines, to estimate cell growth after {gamma} irradiation. Control experiments were conducted on lymphoblastoid cell lines (LCL) and the adherent MCC line, MCC13, to demonstrate that the two assays were comparable under the conditions used. We have examined cell lines from MCC, small cell lung cancer (SCLC), malignant melanomas, Epstein Barr virus (EBV) transformed lymphocytes (LCL), and skin fibroblasts for their sensitivity to {gamma} irradiation using both clonogenic cell survival and MTT assays. The results show that the tumor cell lines have a range of sensitivities, with melanoma being more resistant (surviving fraction at 2 Gy (SF2) 0.57 and 0.56) than the small cell carcinoma lines, MCC (SF2 range 0.21-0.45, mean SF2 0.30, n = 8) and SCLC (SF2 0.31). Fibroblasts were the most sensitive (SF2 0.13-0.20, mean 0.16, n = 5). The MTT assay, when compared to clonogenic assay for the MCC13 adherent line and the LCL, gave comparable results under the conditions used. Both assays gave a range of SF2 values for the MCC cell lines, suggesting that these cancers would give a heterogeneous response in vivo. The results with the two derivative clones of MCC14 (SF2 for MCC14/1 0.38, MCC14/2 0.45) would further suggest that some of them may develop resistance during clonogenic evolution. 25 refs., 3 figs., 1 tab.« less

  8. [Breast carcinoma metastasis to the gastrointestinal tract and tumour-to-tumour metastasis to renal cell carcinoma].

    PubMed

    Mosholt, Karina Sif Søndergaard; Pilt, Anette Pedersen; Wittendorff, Hans-Erik

    2015-04-06

    Breast carcinoma metastasis to the gastrointestinal tract and tumour-to-tumour metastasis is rare. We describe a case of a 71-year-old woman with previous breast cancer presenting with dyspepsia, nausea and weight-loss. Biopsies from the pylorus revealed what appeared to be a gastric carcinoma. A CT scan showed large kidney mass and biopsies revealed clear cell renal cell carcinoma with areas of poorly differentiated adenocarcinoma. Subsequent immunohistochemical analysis revealed the presence of breast carcinoma in both locations.

  9. Sorafenib Tosylate, Cisplatin, and Docetaxel in Treating Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck

    ClinicalTrials.gov

    2018-05-22

    Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Salivary Gland Squamous Cell Carcinoma; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IVA Salivary Gland Cancer; Stage IVA Squamous Cell Carcinoma of the Larynx; Stage IVA Oral Cavity Squamous Cell Carcinoma; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVA Verrucous Carcinoma of the Larynx; Stage IVA Verrucous Carcinoma of the Oral Cavity; Stage IVB Salivary Gland Cancer; Stage IVB Squamous Cell Carcinoma of the Larynx; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVB Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVB Verrucous Carcinoma of the Larynx; Stage IVB Verrucous Carcinoma of the Oral Cavity; Stage IVC Salivary Gland Cancer; Stage IVC Squamous Cell Carcinoma of the Larynx; Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Oropharynx; Stage IVC Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVC Verrucous Carcinoma of the Larynx; Stage IVC Verrucous Carcinoma of the Oral Cavity; Tongue Cancer; Untreated Metastatic Squamous Neck Cancer With Occult Primary

  10. Nevoid basal cell carcinoma syndrome (Gorlin syndrome)

    PubMed Central

    Lo Muzio, Lorenzo

    2008-01-01

    Nevoid basal cell carcinoma syndrome (NBCCS), also known as Gorlin syndrome, is a hereditary condition characterized by a wide range of developmental abnormalities and a predisposition to neoplasms. The estimated prevalence varies from 1/57,000 to 1/256,000, with a male-to-female ratio of 1:1. Main clinical manifestations include multiple basal cell carcinomas (BCCs), odontogenic keratocysts of the jaws, hyperkeratosis of palms and soles, skeletal abnormalities, intracranial ectopic calcifications, and facial dysmorphism (macrocephaly, cleft lip/palate and severe eye anomalies). Intellectual deficit is present in up to 5% of cases. BCCs (varying clinically from flesh-colored papules to ulcerating plaques and in diameter from 1 to 10 mm) are most commonly located on the face, back and chest. The number of BBCs varies from a few to several thousand. Recurrent jaw cysts occur in 90% of patients. Skeletal abnormalities (affecting the shape of the ribs, vertebral column bones, and the skull) are frequent. Ocular, genitourinary and cardiovascular disorders may occur. About 5–10% of NBCCS patients develop the brain malignancy medulloblastoma, which may be a potential cause of early death. NBCCS is caused by mutations in the PTCH1 gene and is transmitted as an autosomal dominant trait with complete penetrance and variable expressivity. Clinical diagnosis relies on specific criteria. Gene mutation analysis confirms the diagnosis. Genetic counseling is mandatory. Antenatal diagnosis is feasible by means of ultrasound scans and analysis of DNA extracted from fetal cells (obtained by amniocentesis or chorionic villus sampling). Main differential diagnoses include Bazex syndrome, trichoepithelioma papulosum multiplex and Torre's syndrome (Muir-Torre's syndrome). Management requires a multidisciplinary approach. Keratocysts are treated by surgical removal. Surgery for BBCs is indicated when the number of lesions is limited; other treatments include laser ablation, photodynamic

  11. Genomic instability in human actinic keratosis and squamous cell carcinoma

    PubMed Central

    Cabral, Luciana Sanches; Neto, Cyro Festa; Sanches, José A; Ruiz, Itamar R G

    2011-01-01

    OBJECTIVE: To compare the repetitive DNA patterns of human actinic keratoses and squamous cell carcinomas to determine the genetic alterations that are associated with malignant transformation. INTRODUCTION: Cancer cells are prone to genomic instability, which is often due to DNA polymerase slippage during the replication of repetitive DNA and to mutations in the DNA repair genes. The progression of benign actinic keratoses to malignant squamous cell carcinomas has been proposed by several authors. MATERIAL AND METHODS: Eight actinic keratoses and 24 squamous cell carcinomas (SCC), which were pair-matched to adjacent skin tissues and/or leucocytes, were studied. The presence of microsatellite instability (MSI) and the loss of heterozygosity (LOH) in chromosomes 6 and 9 were investigated using nine PCR primer pairs. Random Amplified Polymorphic DNA patterns were also evaluated using eight primers. RESULTS: MSI was detected in two (D6S251, D9S50) of the eight actinic keratosis patients. Among the 8 patients who had squamous cell carcinoma-I and provided informative results, a single patient exhibited two LOH (D6S251, D9S287) and two instances of MSI (D9S180, D9S280). Two LOH and one example of MSI (D6S251) were detected in three out of the 10 patients with squamous cell carcinoma-II. Among the four patients with squamous cell carcinoma-III, one patient displayed three MSIs (D6S251, D6S252, and D9S180) and another patient exhibited an MSI (D9S280). The altered random amplified polymorphic DNA ranged from 70% actinic keratoses, 76% squamous cell carcinoma-I, and 90% squamous cell carcinoma-II, to 100% squamous cell carcinoma-III. DISCUSSION: The increased levels of alterations in the microsatellites, particularly in D6S251, and the random amplified polymorphic DNA fingerprints were statistically significant in squamous cell carcinomas, compared with actinic keratoses. CONCLUSION: The overall alterations that were observed in the repetitive DNA of actinic keratoses and

  12. 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.

  13. Understanding Papillary Renal Cell Carcinoma | Center for Cancer Research

    Cancer.gov

    Renal cell carcinoma (RCC), the most common form of kidney cancer in adults, is not a single disease but rather a collection of different tumor types driven by distinct genetic changes that arise within the same tissue.

  14. Adenoid basal cell carcinoma: a rare facet of basal cell carcinoma

    PubMed Central

    Saxena, Kartikay; Manohar, Vidya; Bhakhar, Vikas; Bahl, Sumit

    2016-01-01

    Basal cell carcinoma (BCC) is a common, locally invasive epithelial malignancy of skin and its appendages. Every year, close to 10 million people get diagnosed with BCC worldwide. While the histology of this lesion is mostly predictable, some of the rare histological variants such as cystic, adenoid, morpheaform, infundibulocystic, pigmented and miscellaneous variants (clear-cell, signet ring cell, granular, giant cell, adamantanoid, schwannoid) are even rarer, accounting for <10% of all BCC's. Adenoid BCC (ADBCC) is a very rare histopathological variant with reported incidence of only approximately 1.3%. The clinical appearance of this lesion can be a pigmented or non-pigmented nodule or ulcer without predilection for any particular site. We share a case report of ADBCC, a rare histological variant of BCC that showed interesting features not only histologically but also by clinically mimicking a benign lesion. PMID:27095806

  15. Photodynamic treatment of basal cell carcinoma and squamous cell carcinoma with hypericin.

    PubMed

    Alecu, M; Ursaciuc, C; Hãlãlãu, F; Coman, G; Merlevede, W; Waelkens, E; de Witte, P

    1998-01-01

    Hypericin displays antiproliferative and cytotoxic effects on tumor cells. This effect depends on photodynamic activation with visible light and oxygen. Hence, we explored its potential use in treating skin cancer. Eight patients with squamous cell carcinoma (SCC) and eleven patients with basal cell carcinoma (BCC) were treated topically with hypericin. After intralesional injection, the hypericin was irradiated with visible light. Patients with SCC were given 40-100 micrograms hypericin intralesionally, 3-5 times per week for 2-4 weeks; patients with BCC 40-200 micrograms hypericin 3-5 times per week for 2-6 weeks. Hypericin displayed selective tumor-targeting: penetration in the surrounding tissues did not induce necrosis or cell loss and even the generation of a new epithelium at the surface of the malignancy was noticed. The effectiveness of the therapy depends on the concentration and total dose of hypericin, the frequency and duration of the therapy; clinical remissions can be expected after 6-8 weeks.

  16. β-sitosterol induces G1 arrest and causes depolarization of mitochondrial membrane potential in breast carcinoma MDA-MB-231 cells

    PubMed Central

    2013-01-01

    Backgrounds It is suggested that dietary phytosterols, such as β-sitosterol (ST), have cancer chemopreventive effects; however, studies are limited to support such claims. Here, we evaluated the efficacy of ST on three different human cancer cell lines including skin epidermoid carcinoma A431 cells, lung epithelial carcinoma A549 cells and breast adenocarcinoma MDA-MB-231. Methods Cell growth assay, cell cycle analysis, FACS, JC-1 staining, annexin V staining and immunoblotting were used to study the efficacy of ST on cancer cells. Results ST (30–90 μM) treatments for 48 h and 72 h did not show any significant effect on cell growth and death in A431 cells. Whereas similar ST treatments moderately inhibited the growth of A549 cells by up to 13% (p ≤ 0.05) in 48 h and 14% (p ≤ 0.05-0.0001) in 72 h. In MDA-MB-231 cells, ST caused a significant dose-dependent cell growth inhibition by 31- 63% (p ≤ 0.0001) in 48 h and 40-50% (p ≤ 0.0001) in 72 h. While exploring the molecular changes associated with strong ST efficacy in breast cancer cells, we observed that ST induced cell cycle arrest as well as cell death. ST caused G0/G1 cell cycle arrest which was accompanied by a decrease in CDK4 and cyclin D1, and an increase in p21/Cip1and p27/Kip1 protein levels. Further, cell death effect of ST was associated with induction of apoptosis. ST also caused the depolarization of mitochondrial membrane potential and increased Bax/Bcl-2 protein ratio. Conclusions These results suggest prominent in vitro anti-proliferative and pro-apoptotic effects of ST in MDA-MB-231 cells. This study provides valuable insight into the chemopreventive efficacy and associated molecular alterations of ST in breast cancer cells whereas it had only moderate efficacy on lung cancer cells and did not show any considerable effect on skin cancer cells. These findings would form the basis for further studies to understand the mechanisms and assess the potential utility of ST as a cancer

  17. Corneal squamous cell carcinoma in a Border Collie.

    PubMed

    Busse, Claudia; Sansom, Jane; Dubielzig, R R; Hayes, Alison

    2008-01-01

    A 6-year-old, female, spayed Border Collie was presented to the Unit of Comparative Ophthalmology at the Animal Health Trust with a 6-month history of a progressive nonpainful opacity of the left cornea. A keratectomy was performed and the tissue submitted for histopathology. The diagnosis was squamous cell carcinoma. There has been no recurrence of the neoplasm to date (5 months). Canine corneal squamous cell carcinoma (SCC) has not been reported previously in the UK.

  18. Comprehensive Molecular Characterization of Papillary Renal-Cell Carcinoma.

    PubMed

    Linehan, W Marston; Spellman, Paul T; Ricketts, Christopher J; Creighton, Chad J; Fei, Suzanne S; Davis, Caleb; Wheeler, David A; Murray, Bradley A; Schmidt, Laura; Vocke, Cathy D; Peto, Myron; Al Mamun, Abu Amar M; Shinbrot, Eve; Sethi, Anurag; Brooks, Samira; Rathmell, W Kimryn; Brooks, Angela N; Hoadley, Katherine A; Robertson, A Gordon; Brooks, Denise; Bowlby, Reanne; Sadeghi, Sara; Shen, Hui; Weisenberger, Daniel J; Bootwalla, Moiz; Baylin, Stephen B; Laird, Peter W; Cherniack, Andrew D; Saksena, Gordon; Haake, Scott; Li, Jun; Liang, Han; Lu, Yiling; Mills, Gordon B; Akbani, Rehan; Leiserson, Mark D M; Raphael, Benjamin J; Anur, Pavana; Bottaro, Donald; Albiges, Laurence; Barnabas, Nandita; Choueiri, Toni K; Czerniak, Bogdan; Godwin, Andrew K; Hakimi, A Ari; Ho, Thai H; Hsieh, James; Ittmann, Michael; Kim, William Y; Krishnan, Bhavani; Merino, Maria J; Mills Shaw, Kenna R; Reuter, Victor E; Reznik, Ed; Shelley, Carl S; Shuch, Brian; Signoretti, Sabina; Srinivasan, Ramaprasad; Tamboli, Pheroze; Thomas, George; Tickoo, Satish; Burnett, Kenneth; Crain, Daniel; Gardner, Johanna; Lau, Kevin; Mallery, David; Morris, Scott; Paulauskis, Joseph D; Penny, Robert J; Shelton, Candace; Shelton, W Troy; Sherman, Mark; Thompson, Eric; Yena, Peggy; Avedon, Melissa T; Bowen, Jay; Gastier-Foster, Julie M; Gerken, Mark; Leraas, Kristen M; Lichtenberg, Tara M; Ramirez, Nilsa C; Santos, Tracie; Wise, Lisa; Zmuda, Erik; Demchok, John A; Felau, Ina; Hutter, Carolyn M; Sheth, Margi; Sofia, Heidi J; Tarnuzzer, Roy; Wang, Zhining; Yang, Liming; Zenklusen, Jean C; Zhang, Jiashan; Ayala, Brenda; Baboud, Julien; Chudamani, Sudha; Liu, Jia; Lolla, Laxmi; Naresh, Rashi; Pihl, Todd; Sun, Qiang; Wan, Yunhu; Wu, Ye; Ally, Adrian; Balasundaram, Miruna; Balu, Saianand; Beroukhim, Rameen; Bodenheimer, Tom; Buhay, Christian; Butterfield, Yaron S N; Carlsen, Rebecca; Carter, Scott L; Chao, Hsu; Chuah, Eric; Clarke, Amanda; Covington, Kyle R; Dahdouli, Mahmoud; Dewal, Ninad; Dhalla, Noreen; Doddapaneni, Harsha V; Drummond, Jennifer A; Gabriel, Stacey B; Gibbs, Richard A; Guin, Ranabir; Hale, Walker; Hawes, Alicia; Hayes, D Neil; Holt, Robert A; Hoyle, Alan P; Jefferys, Stuart R; Jones, Steven J M; Jones, Corbin D; Kalra, Divya; Kovar, Christie; Lewis, Lora; Li, Jie; Ma, Yussanne; Marra, Marco A; Mayo, Michael; Meng, Shaowu; Meyerson, Matthew; Mieczkowski, Piotr A; Moore, Richard A; Morton, Donna; Mose, Lisle E; Mungall, Andrew J; Muzny, Donna; Parker, Joel S; Perou, Charles M; Roach, Jeffrey; Schein, Jacqueline E; Schumacher, Steven E; Shi, Yan; Simons, Janae V; Sipahimalani, Payal; Skelly, Tara; Soloway, Matthew G; Sougnez, Carrie; Tam, Angela; Tan, Donghui; Thiessen, Nina; Veluvolu, Umadevi; Wang, Min; Wilkerson, Matthew D; Wong, Tina; Wu, Junyuan; Xi, Liu; Zhou, Jane; Bedford, Jason; Chen, Fengju; Fu, Yao; Gerstein, Mark; Haussler, David; Kasaian, Katayoon; Lai, Phillip; Ling, Shiyun; Radenbaugh, Amie; Van Den Berg, David; Weinstein, John N; Zhu, Jingchun; Albert, Monique; Alexopoulou, Iakovina; Andersen, Jeremiah J; Auman, J Todd; Bartlett, John; Bastacky, Sheldon; Bergsten, Julie; Blute, Michael L; Boice, Lori; Bollag, Roni J; Boyd, Jeff; Castle, Erik; Chen, Ying-Bei; Cheville, John C; Curley, Erin; Davies, Benjamin; DeVolk, April; Dhir, Rajiv; Dike, Laura; Eckman, John; Engel, Jay; Harr, Jodi; Hrebinko, Ronald; Huang, Mei; Huelsenbeck-Dill, Lori; Iacocca, Mary; Jacobs, Bruce; Lobis, Michael; Maranchie, Jodi K; McMeekin, Scott; Myers, Jerome; Nelson, Joel; Parfitt, Jeremy; Parwani, Anil; Petrelli, Nicholas; Rabeno, Brenda; Roy, Somak; Salner, Andrew L; Slaton, Joel; Stanton, Melissa; Thompson, R Houston; Thorne, Leigh; Tucker, Kelinda; Weinberger, Paul M; Winemiller, Cynthia; Zach, Leigh Anne; Zuna, Rosemary

    2016-01-14

    Papillary renal-cell carcinoma, which accounts for 15 to 20% of renal-cell carcinomas, is a heterogeneous disease that consists of various types of renal cancer, including tumors with indolent, multifocal presentation and solitary tumors with an aggressive, highly lethal phenotype. Little is known about the genetic basis of sporadic papillary renal-cell carcinoma, and no effective forms of therapy for advanced disease exist. We performed comprehensive molecular characterization of 161 primary papillary renal-cell carcinomas, using whole-exome sequencing, copy-number analysis, messenger RNA and microRNA sequencing, DNA-methylation analysis, and proteomic analysis. Type 1 and type 2 papillary renal-cell carcinomas were shown to be different types of renal cancer characterized by specific genetic alterations, with type 2 further classified into three individual subgroups on the basis of molecular differences associated with patient survival. Type 1 tumors were associated with MET alterations, whereas type 2 tumors were characterized by CDKN2A silencing, SETD2 mutations, TFE3 fusions, and increased expression of the NRF2-antioxidant response element (ARE) pathway. A CpG island methylator phenotype (CIMP) was observed in a distinct subgroup of type 2 papillary renal-cell carcinomas that was characterized by poor survival and mutation of the gene encoding fumarate hydratase (FH). Type 1 and type 2 papillary renal-cell carcinomas were shown to be clinically and biologically distinct. Alterations in the MET pathway were associated with type 1, and activation of the NRF2-ARE pathway was associated with type 2; CDKN2A loss and CIMP in type 2 conveyed a poor prognosis. Furthermore, type 2 papillary renal-cell carcinoma consisted of at least three subtypes based on molecular and phenotypic features. (Funded by the National Institutes of Health.).

  19. Primary mucoepidermoid carcinoma of the lung with prominent clear cells

    PubMed Central

    Fink, David D.; Lomas, Angela M.; Roden, Anja C.; Shah, Prashant C.

    2017-01-01

    Mucoepidermoid carcinoma of the lung is a rare malignancy of salivary gland-type origin. We report a case of a 21-year-old man with a right mainstem bronchus mass composed predominantly of clear cells. This case represents a rare primary pulmonary low-grade mucoepidermoid carcinoma positive for MAML2 rearrangement by fluorescence in situ hybridization with a prominent clear cell component. PMID:28670072

  20. Comprehensive Molecular Characterization of Papillary Renal Cell Carcinoma

    PubMed Central

    Linehan, W. Marston; Spellman, Paul T.; Ricketts, Christopher J.; Creighton, Chad J.; Fei, Suzanne S.; Davis, Caleb; Wheeler, David A.; Murray, Bradley A.; Schmidt, Laura; Vocke, Cathy D.; Peto, Myron; Al Mamun, Abu Amar M.; Shinbrot, Eve; Sethi, Anurag; Brooks, Samira; Rathmell, W. Kimryn; Brooks, Angela N.; Hoadley, Katherine A.; Robertson, A. Gordon; Brooks, Denise; Bowlby, Reanne; Sadeghi, Sara; Shen, Hui; Weisenberger, Daniel J.; Bootwalla, Moiz; Baylin, Stephen B.; Laird, Peter W.; Cherniack, Andrew D.; Saksena, Gordon; Haake, Scott; Li, Jun; Liang, Han; Lu, Yiling; Mills, Gordon B.; Akbani, Rehan; Leiserson, Mark D.M.; Raphael, Benjamin J.; Anur, Pavana; Bottaro, Donald; Albiges, Laurence; Barnabas, Nandita; Choueiri, Toni K.; Czerniak, Bogdan; Godwin, Andrew K.; Hakimi, A. Ari; Ho, Thai; Hsieh, James; Ittmann, Michael; Kim, William Y.; Krishnan, Bhavani; Merino, Maria J.; Mills Shaw, Kenna R.; Reuter, Victor E.; Reznik, Ed; Shelley, Carl Simon; Shuch, Brian; Signoretti, Sabina; Srinivasan, Ramaprasad; Tamboli, Pheroze; Thomas, George; Tickoo, Satish; Burnett, Kenneth; Crain, Daniel; Gardner, Johanna; Lau, Kevin; Mallery, David; Morris, Scott; Paulauskis, Joseph D.; Penny, Robert J.; Shelton, Candace; Shelton, W. Troy; Sherman, Mark; Thompson, Eric; Yena, Peggy; Avedon, Melissa T.; Bowen, Jay; Gastier-Foster, Julie M.; Gerken, Mark; Leraas, Kristen M.; Lichtenberg, Tara M.; Ramirez, Nilsa C.; Santos, Tracie; Wise, Lisa; Zmuda, Erik; Demchok, John A.; Felau, Ina; Hutter, Carolyn M.; Sheth, Margi; Sofia, Heidi J.; Tarnuzzer, Roy; Wang, Zhining; Yang, Liming; Zenklusen, Jean C.; Zhang, Jiashan (Julia); Ayala, Brenda; Baboud, Julien; Chudamani, Sudha; Liu, Jia; Lolla, Laxmi; Naresh, Rashi; Pihl, Todd; Sun, Qiang; Wan, Yunhu; Wu, Ye; Ally, Adrian; Balasundaram, Miruna; Balu, Saianand; Beroukhim, Rameen; Bodenheimer, Tom; Buhay, Christian; Butterfield, Yaron S.N.; Carlsen, Rebecca; Carter, Scott L.; Chao, Hsu; Chuah, Eric; Clarke, Amanda; Covington, Kyle R.; Dahdouli, Mahmoud; Dewal, Ninad; Dhalla, Noreen; Doddapaneni, HarshaVardhan; Drummond, Jennifer; Gabriel, Stacey B.; Gibbs, Richard A.; Guin, Ranabir; Hale, Walker; Hawes, Alicia; Hayes, D. Neil; Holt, Robert A.; Hoyle, Alan P.; Jefferys, Stuart R.; Jones, Steven J.M.; Jones, Corbin D.; Kalra, Divya; Kovar, Christie; Lewis, Lora; Li, Jie; Ma, Yussanne; Marra, Marco A.; Mayo, Michael; Meng, Shaowu; Meyerson, Matthew; Mieczkowski, Piotr A.; Moore, Richard A.; Morton, Donna; Mose, Lisle E.; Mungall, Andrew J.; Muzny, Donna; Parker, Joel S.; Perou, Charles M.; Roach, Jeffrey; Schein, Jacqueline E.; Schumacher, Steven E.; Shi, Yan; Simons, Janae V.; Sipahimalani, Payal; Skelly, Tara; Soloway, Matthew G.; Sougnez, Carrie; Tam, Angela; Tan, Donghui; Thiessen, Nina; Veluvolu, Umadevi; Wang, Min; Wilkerson, Matthew D.; Wong, Tina; Wu, Junyuan; Xi, Liu; Zhou, Jane; Bedford, Jason; Chen, Fengju; Fu, Yao; Gerstein, Mark; Haussler, David; Kasaian, Katayoon; Lai, Phillip; Ling, Shiyun; Radenbaugh, Amie; Van Den Berg, David; Weinstein, John N.; Zhu, Jingchun; Albert, Monique; Alexopoulou, Iakovina; Andersen, Jeremiah J; Auman, J. Todd; Bartlett, John; Bastacky, Sheldon; Bergsten, Julie; Blute, Michael L.; Boice, Lori; Bollag, Roni J.; Boyd, Jeff; Castle, Erik; Chen, Ying-Bei; Cheville, John C.; Curley, Erin; Davies, Benjamin; DeVolk, April; Dhir, Rajiv; Dike, Laura; Eckman, John; Engel, Jay; Harr, Jodi; Hrebinko, Ronald; Huang, Mei; Huelsenbeck-Dill, Lori; Iacocca, Mary; Jacobs, Bruce; Lobis, Michael; Maranchie, Jodi K.; McMeekin, Scott; Myers, Jerome; Nelson, Joel; Parfitt, Jeremy; Parwani, Anil; Petrelli, Nicholas; Rabeno, Brenda; Roy, Somak; Salner, Andrew L.; Slaton, Joel; Stanton, Melissa; Thompson, R. Houston; Thorne, Leigh; Tucker, Kelinda; Weinberger, Paul M.; Winemiller, Cythnia; Zach, Leigh Anne; Zuna, Rosemary

    2016-01-01

    Background Papillary renal cell carcinoma, accounting for 15% of renal cell carcinoma, is a heterogeneous disease consisting of different types of renal cancer, including tumors with indolent, multifocal presentation and solitary tumors with an aggressive, highly lethal phenotype. Little is known about the genetic basis of sporadic papillary renal cell carcinoma; no effective forms of therapy for advanced disease exist. Methods We performed comprehensive molecular characterization utilizing whole-exome sequencing, copy number, mRNA, microRNA, methylation and proteomic analyses of 161 primary papillary renal cell carcinomas. Results Type 1 and Type 2 papillary renal cell carcinomas were found to be different types of renal cancer characterized by specific genetic alterations, with Type 2 further classified into three individual subgroups based on molecular differences that influenced patient survival. MET alterations were associated with Type 1 tumors, whereas Type 2 tumors were characterized by CDKN2A silencing, SETD2 mutations, TFE3 fusions, and increased expression of the NRF2-ARE pathway. A CpG island methylator phenotype (CIMP) was found in a distinct subset of Type 2 papillary renal cell carcinoma characterized by poor survival and mutation of the fumarate hydratase (FH) gene. Conclusions Type 1 and Type 2 papillary renal cell carcinomas are clinically and biologically distinct. Alterations in the MET pathway are associated with Type 1 and activation of the NRF2-ARE pathway with Type 2; CDKN2A loss and CIMP in Type 2 convey a poor prognosis. Furthermore, Type 2 papillary renal cell carcinoma consists of at least 3 subtypes based upon molecular and phenotypic features. PMID:26536169

  1. Paget's disease of the urethral meatus following transitional cell carcinoma of the bladder.

    PubMed

    Tomaszewski, J E; Korat, O C; LiVolsi, V A; Connor, A M; Wein, A

    1986-02-01

    Pagetoid extension of transitional cell carcinoma onto the urethral meatus following cystectomy is a rare complication of bladder carcinoma. We report 2 cases associated with severe dysplasia and carcinoma in situ of the periurethral glands.

  2. Primary pure spindle cell carcinoma (sarcomatoid carcinoma) of the ovary: A case report with immunohistochemical study.

    PubMed

    Giordano, Giovanna; Berretta, Roberto; Silini, Enrico

    2016-08-05

    In the ovary, sarcomatoid carcinoma has been reported only as mural nodules in epithelial malignant or borderline serous or mucinous cystic neoplasms, and in teratomas. In this paper we report a rare case of a solid sarcomatoid carcinoma of the ovary, without accompanying component of giant cells, pleomorphic cells, or glandular and other epithelial structures. This case report refers to a sarcomatoid carcinoma of the ovary in in a 57 year-old woman with abdominal pain. Macroscopically, the neoplasm was a 15x10x5 cm ovarian mass that featured gray white solid fleshy areas, interspersed with areas of necrosis, hemorrhage and cystic spaces filled with thick fluid. The epithelial differentiation of the tumor was demonstrated by strong and diffuse reactivity to CAM5.2 and focal immunoreactivity to EMA. A diagnosis of malignant mesenchymal tumor was excluded due to negativity for desmin, smooth muscle actin, caldesmon, CD34, CD10, and myoglobin. Neural, neuroendocrine neoplasm, melanoma and Perivascular Epithelioid Cell Tumor (PEComa) were excluded because of negativity for S100, chromogranin, synaptophysin and HMB45. Primary ovarian spindle cell carcinoma is a rare neoplasm, which must be considered in the differential diagnosis of solid ovarian mass with spindle cell appearance. This case adds to our knowledge of the biological behavior of these rare neoplasms. The distinction from true sarcomas and carcinosarcomas is important because of the more favorable prognosis of the spindle cell carcinomas. However their diagnosis necessitates a careful tissue sampling and immunohistochemical staining.

  3. Chemotherapy With or Without Bevacizumab in Treating Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

    ClinicalTrials.gov

    2018-06-19

    Recurrent Hypopharyngeal Squamous Cell Carcinoma; Recurrent Laryngeal Squamous Cell Carcinoma; Recurrent Laryngeal Verrucous Carcinoma; Recurrent Lip and Oral Cavity Squamous Cell Carcinoma; Recurrent Metastatic Squamous Cell Carcinoma in the Neck With Occult Primary; Recurrent Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Recurrent Oral Cavity Verrucous Carcinoma; Recurrent Oropharyngeal Squamous Cell Carcinoma; Recurrent Salivary Gland Carcinoma; Salivary Gland Squamous Cell Carcinoma; Squamous Cell Carcinoma Metastatic in the Neck With Occult Primary; Stage IV Hypopharyngeal Squamous Cell Carcinoma AJCC v7; Stage IV Major Salivary Gland Cancer AJCC v7; Stage IVA Laryngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Laryngeal Verrucous Carcinoma AJCC v7; Stage IVA Lip and Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVA Major Salivary Gland Cancer AJCC v7; Stage IVA Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v7; Stage IVA Oral Cavity Cancer AJCC v6 and v7; Stage IVA Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Laryngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Laryngeal Verrucous Carcinoma AJCC v7; Stage IVB Lip and Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVB Major Salivary Gland Cancer AJCC v7; Stage IVB Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v7; Stage IVB Oral Cavity Cancer AJCC v6 and v7; Stage IVB Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVC Laryngeal Squamous Cell Carcinoma AJCC v7; Stage IVC Laryngeal Verrucous Carcinoma AJCC v7; Stage IVC Lip and Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVC Major Salivary Gland Cancer AJCC v7; Stage IVC Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v7; Stage IVC Oral Cavity Cancer AJCC v6 and v7; Stage IVC Oropharyngeal Squamous Cell Carcinoma AJCC v7; Tongue Carcinoma; Untreated Metastatic Squamous Cell Carcinoma to Neck With Occult Primary

  4. ELF5 in epithelial ovarian carcinoma tissues and biological behavior in ovarian carcinoma cells.

    PubMed

    Yan, Hongchao; Qiu, Linglin; Xie, Xiaolei; Yang, He; Liu, Yongli; Lin, Xiaoman; Huang, Hongxiang

    2017-03-01

    The expression of E74-like factor 5 (ELF5) in epithelial ovarian carcinoma tissues and its effects on biological behavior in ovarian carcinoma cells were assessed in search for a new approach for gene treatment of epithelial ovarian carcinoma. RT-PCR technology was applied to detect the expression of ELF5 mRNA in epithelial ovarian carcinoma (n=49), borderline ovarian epithelial tumor (n=19), benign ovarian epithelial tumor (n=31) and normal ovarian tissues (n=40). Then, we transfected recombinant plasmid pcDNA3.1‑ELF5+EGFP into human ovarian carcinoma SKOV3 cells (recombinant plasmid group) in vitro and screened out stably transfected cells to conduct multiplication culture. Western blot analysis was performed to detect the expression of ELF5 protein in the different groups. Flow cytometry was employed to detect cell apoptosis and cycles. ELF5 mRNA in epithelial ovarian carcinoma and borderline ovarian epithelial tumor tissues were significantly lower (P<0.05) than those in benign ovarian epithelial tumor and normal ovarian tissues. ELF5 protein expression in the cells of recombinant plasmid group was significantly higher compared with empty plasmid and blank control groups. The capacity of cell reproductive recombinant plasmid group at each time point decreased (P<0.05). Flow cytometry detection showed that 67.03% of cells in recombinant plasmid group was blocked in G0/G1 phase (P<0.05), compared with empty plasmid group (37.17%) and blank control group (38.24%). Apoptotic rate of recombinant plasmid group was significantly lower (31.4±1.9%; P<0.05), compared with that of empty plasmid group (9.1±2.2%) and blank control group (8.7±1.5%), and the differences were statistically significant. In conclusion, ELF5 interfered with cell cycle of human ovarian carcinoma SKOV3 cells and promoted apoptosis of human ovarian carcinoma SKOV3 cells inhibiting their growth and invasive capacity; and thus providing a new approach to gene treatment of ovarian carcinoma.

  5. [Immunotherapy for renal cell carcinoma - current status].

    PubMed

    Grimm, Marc-Oliver; Foller, Susan

    2018-04-01

    Systemic treatment of metastatic renal cell carcinoma (mRCC) has substantially changed during the last 2 years due to approval of the immune-checkpoint inhibitor Nivolumab (Opdivo ® ) and new multikinase inhibitors (Cabozantinib, Lenvatinib, Tivozanib). The german kidney tumor guideline strongly recommends Nivolumab and Cabozantinib as 2nd line treatments after prior VEGF targeted therapy. CheckMate 025, the prospective randomized trial which led to approval of Nivolumab demonstrated improved overall survival (26 month vs. 19.7 month; hazard ratio 0.73; p = 0.0006) and response rate (26 % vs. 5 %) as well as a favorable toxicity profile compared with Everolimus. Currently, numerous combinations with PD-1/PD-L1 inhibitors are compared to Sunitinib as first line treatment of mRCC. Out of these CheckMate 214, a randomized phase-3 trial is the first to demonstrate a significant higher objective response rate (42 % vs. 27 %, p < 0.0001) and overall survival (Sunitinib 26.0 month, median for Nivo + Ipi has been not yet reached (28.2 - NR); Hazard ratio 0.63) for the combination of Nivolumab and the CTLA-4 antibody Ipilimumab in IMDC intermediate and high risk patients. Furthermore, CheckMate 214 shows better side effect profile and quality of life in patients receiving Nivolumab and Ipilimumab compared with Sunitinib. However, a considerable increase of immune related adverse events is associated with the immune combination therapy. Another randomized trial demonstrates improved progression-free survival for the combination of the PD-L1 inhibitor Atezolizumab and the VEGF antibody Bevacizumab in patients with PD-L1 positive tumors; this was found in all IMDC risk groups. Further phase-3 trials with "new" VEGFR-TKIs (Axitinib, Cabozantinib, Lenvatinib) and PD-1/PD-L1 inhibitor combinations are ongoing.In conclusion, the PD-1 immune checkpoint inhibitor Nivolumab will remain a standard treatment for patients with metastatic renal cell carcinoma

  6. Unusual mucoepidermoid carcinoma of the liver misdiagnosed as squamous cell carcinoma by intraoperative histological examination

    PubMed Central

    2014-01-01

    As rare condition, mucoepidermoid carcinoma may occur in liver although its etiology and pathogenesis is still unclear. We report here a case of intrahepatic mucoepidermoid carcinoma misdiagnosed as cholangiocarcinoma and squamous cell carcinoma by preoperative radiologic and intraoperative histological examinations, respectively. A 60-year-old woman presented with a 1-month history of progressive jaundice, epigastric discomfort, and weight loss with slightly increased carbohydrate antigen 19-9 (CA19-9). Computed tomography (CT) showed a large tumor, 8.0 cm in diameter, in the left lobe of the liver. A preliminary diagnosis of a cholangiocarcinoma of the liver was made. In the intraoperative histological examination, a diagnosis of squamous cell carcinoma was made based on predominantly invasive epidermoid cells with abundant keratinization and absence of mucin-producing cell component. However, postoperative histological diagnosis of the lesion was mucoepidermiod carcinoma of liver by thoroughly microscopical inspection and the presence of mucin-producing cells confirmed by Alcian blue staining. Despite surgical excision and chemotherapy, the tumor showed very aggressive malignancy with tumor recurrence. The patient died shortly afterward, surviving 6 months after surgery. Due to its rarity and distinct morphological features, mucoepidermoid carcinoma might be erroneously interpreted as squamous cell carcinoma by those who were not familiar with this condition in unusual locations. Therefore, removal of sufficient tissue from different portions of the lesion is essential for the surgeons and pathologists to make a precise diagnosis in the intraoperative histological examination. Virtual slide The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/4956311271136060 PMID:24475740

  7. Erlotinib in Treating Patients With Advanced Non-Small Cell Lung Cancer, Ovarian Cancer, or Squamous Cell Carcinoma of the Head and Neck

    ClinicalTrials.gov

    2013-01-08

    Recurrent Non-small Cell Lung Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Nasopharynx; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage IIIA Non-small Cell Lung Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IIIB Ovarian Epithelial Cancer; Stage IIIC Ovarian Epithelial Cancer; Stage IV Non-small Cell Lung Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IVA Squamous Cell Carcinoma of the Larynx; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVB Squamous Cell Carcinoma of the Larynx; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVC Squamous Cell Carcinoma of the Larynx; Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Oropharynx

  8. Cutaneous squamous and neuroendocrine carcinoma: genetically and immunohistochemically different from Merkel cell carcinoma

    PubMed Central

    Pulitzer, Melissa P; Brannon, A Rose; Berger, Michael F; Louis, Peter; Scott, Sasinya N; Jungbluth, Achim A; Coit, Daniel G; Brownell, Isaac; Busam, Klaus J

    2016-01-01

    Cutaneous neuroendocrine (Merkel cell) carcinoma most often arises de novo in the background of a clonally integrated virus, the Merkel cell polyomavirus, and is notable for positive expression of retinoblastoma 1 (RB1) protein and low expression of p53 compared with the rare Merkel cell polyomavirus-negative Merkel cell carcinomas. Combined squamous and Merkel cell tumors are consistently negative for Merkel cell polyomavirus. Little is known about their immunophenotypic or molecular profile. Herein, we studied 10 combined cutaneous squamous cell and neuroendocrine carcinomas for immunohistochemical expression of p53, retinoblastoma 1 protein, neurofilament, p63, and cytokeratin 20 (CK20). We compared mutation profiles of five combined Merkel cell carcinomas and seven ‘pure’ Merkel cell carcinomas using targeted next-generation sequencing. Combined tumors were from the head, trunk, and leg of Caucasian males and one female aged 52–89. All cases were highly p53- and p63-positive and neurofilament-negative in the squamous component, whereas RB1-negative in both components. Eight out of 10 were p53-positive, 3/10 p63-positive, and 3/10 focally neurofilament-positive in the neuroendocrine component. Six out of 10 were CK20-positive in any part. By next-generation sequencing, combined tumors were highly mutated, with an average of 48 mutations per megabase compared with pure tumors, which showed 1.25 mutations per megabase. RB1 and p53 mutations were identified in all five combined tumors. Combined tumors represent an immunophenotypically and genetically distinct variant of primary cutaneous neuroendocrine carcinomas, notable for a highly mutated genetic profile, significant p53 expression and/or mutation, absent RB1 expression in the context of increased RB1 mutation, and minimal neurofilament expression. PMID:26022453

  9. Cutaneous squamous and neuroendocrine carcinoma: genetically and immunohistochemically different from Merkel cell carcinoma.

    PubMed

    Pulitzer, Melissa P; Brannon, A Rose; Berger, Michael F; Louis, Peter; Scott, Sasinya N; Jungbluth, Achim A; Coit, Daniel G; Brownell, Isaac; Busam, Klaus J

    2015-08-01

    Cutaneous neuroendocrine (Merkel cell) carcinoma most often arises de novo in the background of a clonally integrated virus, the Merkel cell polyomavirus, and is notable for positive expression of retinoblastoma 1 (RB1) protein and low expression of p53 compared with the rare Merkel cell polyomavirus-negative Merkel cell carcinomas. Combined squamous and Merkel cell tumors are consistently negative for Merkel cell polyomavirus. Little is known about their immunophenotypic or molecular profile. Herein, we studied 10 combined cutaneous squamous cell and neuroendocrine carcinomas for immunohistochemical expression of p53, retinoblastoma 1 protein, neurofilament, p63, and cytokeratin 20 (CK20). We compared mutation profiles of five combined Merkel cell carcinomas and seven 'pure' Merkel cell carcinomas using targeted next-generation sequencing. Combined tumors were from the head, trunk, and leg of Caucasian males and one female aged 52-89. All cases were highly p53- and p63-positive and neurofilament-negative in the squamous component, whereas RB1-negative in both components. Eight out of 10 were p53-positive, 3/10 p63-positive, and 3/10 focally neurofilament-positive in the neuroendocrine component. Six out of 10 were CK20-positive in any part. By next-generation sequencing, combined tumors were highly mutated, with an average of 48 mutations per megabase compared with pure tumors, which showed 1.25 mutations per megabase. RB1 and p53 mutations were identified in all five combined tumors. Combined tumors represent an immunophenotypically and genetically distinct variant of primary cutaneous neuroendocrine carcinomas, notable for a highly mutated genetic profile, significant p53 expression and/or mutation, absent RB1 expression in the context of increased RB1 mutation, and minimal neurofilament expression.

  10. Hypofractionated Radiation Therapy Followed by Surgery in Treating Patients With Advanced Squamous Cell Carcinoma of the Oral Cavity

    ClinicalTrials.gov

    2017-11-15

    Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Verrucous Carcinoma of the Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Verrucous Carcinoma of the Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Verrucous Carcinoma of the Oral Cavity; Tongue Cancer

  11. Cytokeratin 20-negative Merkel cell carcinoma is infrequently associated with the Merkel cell polyomavirus.

    PubMed

    Miner, Andrew G; Patel, Rajiv M; Wilson, Deborah A; Procop, Gary W; Minca, Eugen C; Fullen, Douglas R; Harms, Paul W; Billings, Steven D

    2015-04-01

    Merkel cell carcinoma is a rare, highly aggressive cutaneous neuroendocrine carcinoma most commonly seen in sun-damaged skin. Histologically, the tumor consists of primitive round cells with fine chromatin and numerous mitoses. Immunohistochemical stains demonstrate expression of neuroendocrine markers. In addition, cytokeratin 20 (CK20) is expressed in ∼95% of cases. In 2008, Merkel cell carcinoma was shown to be associated with a virus now known as Merkel cell polyomavirus in ∼80% of cases. Prognostic and mechanistic differences between Merkel cell polyomavirus-positive and Merkel cell polyomavirus-negative Merkel cell carcinoma may exist. There has been the suggestion that CK20-negative Merkel cell carcinomas less frequently harbor Merkel cell polyomavirus, but a systematic investigation for Merkel cell polyomavirus incidence in CK20-negative Merkel cell carcinoma has not been done. To test the hypothesis that Merkel cell polyomavirus is less frequently associated with CK20-negative Merkel cell carcinoma, we investigated 13 CK20-negative Merkel cell carcinomas from the files of the Cleveland Clinic and the University of Michigan for the virus. The presence or absence of Merkel cell polyomavirus was determined by quantitative PCR performed for Large T and small T antigens, with sequencing of PCR products to confirm the presence of Merkel cell polyomavirus. Ten of these (77%) were negative for Merkel cell polyomavirus and three (23%) were positive for Merkel cell polyomavirus. Merkel cell polyomavirus is less common in CK20-negative Merkel cell carcinoma. Larger series and clinical follow-up may help to determine whether CK20-negative Merkel cell carcinoma is mechanistically and prognostically unique.

  12. Adjuvant therapy for advanced renal cell carcinoma.

    PubMed

    Meissner, Matthew A; McCormick, Barrett Z; Karam, Jose A; Wood, Christopher G

    2018-07-01

    Locally advanced, non-metastatic renal cell carcinoma (RCC) is conventionally managed with surgery. However, patients are at a high risk of RCC recurrence and have poor survival outcomes. An effective adjuvant systemic treatment is needed to improve on these outcomes. Targeted molecular and immune-based therapies have been investigated, or are under investigation, but their role in this setting remains unclear. Areas covered: A comprehensive search of PubMed and ClinicalTrials.gov was performed for relevant literature. The following topics pertinent to adjuvant therapy in RCC were evaluated: strategies for patient selection, cytokine-based immunotherapy, vaccine therapy, VEGF and non-VEGF targeted molecular agents, and immune checkpoint inhibitors. Expert commentary: Strong evidence for the incorporation of adjuvant therapy in high-risk RCC is lacking. Multiple targeted molecular therapies have been examined with only one approved for use. Genetic and molecular-based prognostic models are needed to determine who may benefit from adjuvant therapy. Developing adjuvant therapy strategies in the future depends on the results of important ongoing trials with immunotherapy and targeted agents.

  13. Segregation analysis of urothelial cell carcinoma.

    PubMed

    Aben, Katja K H; Baglietto, Laura; Baffoe-Bonnie, Agnes; Coebergh, Jan-Willem W; Bailey-Wilson, Joan E; Trink, Barry; Verbeek, André L M; Schoenberg, Mark P; Alfred Witjes, J; Kiemeney, Lambertus A

    2006-07-01

    A family history of urothelial cell carcinoma (UCC) confers an almost two-fold increased risk of developing UCC. It is unknown whether (part of) this aggregation of UCC has a Mendelian background. We performed complex segregation analyses on 1193 families ascertained through a proband with UCC of the bladder, ureter, renal pelvis or urethra, who were newly diagnosed between January 1, 1995 and December 31, 1997 and registered by two population-based cancer registries in the southeastern part of the Netherlands. Data were reported on 10 738 first-degree relatives by postal questionnaire; 101 of these relatives had UCC. All reported occurrences of UCC were verified (if possible) using medical records. Analyses were performed with the S.A.G.E. segregation package. Five restricted models (Mendelian dominant, Mendelian recessive, Mendelian co-dominant, 'no major gene' model and environmental model) were tested against the general unrestricted model. Sex and smoking status were incorporated as covariates. Strong evidence of Mendelian inheritance of UCC through a single major gene was not found in these 1 193 families. However, since none of the Mendelian models could be rejected, an inherited subtype of UCC cannot be excluded. A major gene may segregate in some families but this effect may have been masked in a background of high sporadic incidence. The 'no major gene' (or sporadic) model appeared to be the most parsimonious one to describe the occurrence of UCC in these families.

  14. Cell-Matrix Interactions in Breast Carcinoma Invasion.

    DTIC Science & Technology

    1998-01-01

    concentrated in hemidesmosomes, adhesive junctions which connect the basement membrane to the intracellular keratin cytoskeleton. In virtually all...fibronectin receptor contribute to the adhesive abnormalities of transformed fibroblasts by overexpressing this integrin in Chinese hamster ovary (CHO) cells...normal breast epithelium , the integrins expressed in breast carcinoma cells are diffusely distributed over the cell surface (Zutter et al., 1990

  15. Mucinous breast carcinoma with myoepithelial-like spindle cells.

    PubMed

    Miyake, Yasuyuki; Hirokawa, Mitsuyoshi; Norimatsu, Yoshiaki; Kanahara, Takuo; Monobe, Yasumasa; Ohno, Setsuyo; Miyamoto, Tomoyuki; Yakushiji, Hiromasa; Sakaguchi, Takuya; Aratake, Yatsuki; Ohno, Eiji

    2009-06-01

    Appearance of spindle cells has been believed as a benign index of breast cytology. But, we have frequently observed the spindle cells in smears from mucinous carcinoma of the breast. Here, we characterized the biochemical nature of the spindle cells, so as to clarify their identity in cytology. Nineteen cases of breast mucinous carcinoma were used for cytological examination. The spindle cells were located at edges of tumor cell nests and in the backgrounds of cytological specimens. Immunohistological examination revealed that the spindle cells exhibited both immunoreactivity against carcinoembryonic antigen (CEA) and epithelial membrane antigen (EMA). Immunoreactivity against vimentin, cytokeratin, or alpha-smooth muscle actin was, however, not observed. The mode of distribution of biochemical markers suggests that the positive cells for anti-CEA antibody and anti-EMA antibody are tumor cells compressed by mucin, while the vimentin-positive cells are fibroblasts. We assert that the presence of spindle cells can be a characteristic feature of mucinous carcinoma of the breast. Discrimination of the spindle cells in mucinous carcinoma from myoepithelial cells and naked bipolar nuclei in benign lesions was established here. It should facilitate precise diagnosis of breast cancer. (c) 2009 Wiley-Liss, Inc.

  16. Synchronous Parotid (Mammary Analog) Secretory Carcinoma and Acinic Cell Carcinoma: Report of a Case.

    PubMed

    Mossinelli, C; Pigni, C; Sovardi, F; Occhini, A; Preda, L; Benazzo, M; Morbini, P; Pagella, F

    2018-06-06

    Mammary analogue secretory carcinoma (MASC) is a recently described low-grade salivary gland malignancy with histologic, immunohistochemical and molecular similarities to secretory carcinoma of the breast, including a specific t(12;15)(p13;q25) resulting in an ETV6-NTRK3 gene fusion. Ultrasound and magnetic resonance imaging frequently document a macrocystic structure. The main differential diagnosis of secretory carcinoma is with low grade acinic cell carcinoma (AciCC). The two can be differentiated with immunohistochemical stains for S100, mammaglobin, carbonic anhydrase VI and DOG-1; the identification of the specific translocation can help to characterize non-typical cases. We report a unique case of synchronous MASC and AciCC presenting in a parotid gland and discuss the implications of the correct identification of the two tumors.

  17. Vismodegib (ERIVEDGE°) In basal cell carcinoma: too many unknowns.

    PubMed

    2015-01-01

    Basal cell carcinomas are the most common skin cancers. They are usually localised and carry a good prognosis. There is no standard treatment for the rare patients with metastatic basal cell carcinoma or very extensive basal cell carcinoma for whom surgery or radiotherapy is inappropriate. Vismodegib, a cytotoxic drug, is claimed to prevent tumour growth by inhibiting a pathway involved in tissue repair and embryogenesis. It has been authorised in the European Union for patients with metastatic or locally advanced and extensive basal cell carcinoma. Clinical evaluation of vismodegib is based on a non-comparative clinical trial involving 104 patients, providing only weak evidence. Twenty-one months after the start of the trial, 7 patients with metastases (21%) and 6 patients with advanced basal cell carcinoma (10%) had died. Given the lack of a placebo group, there is no way of knowing whether vismodegib had any effect, positive or negative, on survival. There were no complete responses among patients with metastases, but about one-third of them had partial responses. Among the 63 patients with locally advanced basal cell carcinoma, there were 14 complete responses and 16 partial responses. The recurrence rate in patients with complete responses was not reported. Similar results were reported in two other uncontrolled trials available in mid-2014. Vismodegib has frequent and sometimes serious adverse effects, including muscle spasms, fatigue and severe hyponatraemia. Cases of severe weight loss, alopecia, ocular disorders, other cancers (including squamous cell carcinoma) and anaemia have also been reported. More data are needed on possible hepatic and cardiovascular adverse effects. A potent teratogenic effect was seen in experimental animals. As vismodegib enters semen, contraception is mandatory for both men (condoms) and women. In practice, vismodegib has frequent and varied adverse effects, some of which are serious, while its benefits are poorly documented

  18. Expression of Cat Podoplanin in Feline Squamous Cell Carcinomas.

    PubMed

    Itai, Shunsuke; Yamada, Shinji; Kaneko, Mika K; Harada, Hiroyuki; Kagawa, Yumiko; Konnai, Satoru; Kato, Yukinari

    2017-12-01

    Oral squamous cell carcinoma is an aggressive tumor in cats; however, molecular-targeted therapies against this tumor, including antibody therapy, have not been developed. Sensitive and specific monoclonal antibodies (mAbs) against highly expressed membrane proteins are needed to develop antibody therapies. Podoplanin, a type I transmembrane glycoprotein, is expressed in many human malignant tumors, including brain tumor, esophageal cancer, lung cancer, mesothelioma, and oral cancer. Podoplanin binds to C-type lectin-like receptor-2 (CLEC-2) and activates platelet aggregation, which is involved in cancer metastasis. Until now, we have established several mAbs against podoplanin in humans, mice, rats, rabbits, dogs, cattle, and cats. We have reported podoplanin expression in canine melanoma and squamous cell carcinomas using an anti-dog podoplanin mAb PMab-38. In this study, we investigated podoplanin expression in 40 feline squamous cell carcinomas (14 cases of mouth floor, 13 of skin, 9 of ear, and 4 of tongue) by immunohistochemical analysis using an anti-cat podoplanin mAb PMab-52, which we recently developed by cell-based immunization and screening (CBIS) method. Of the total 40 cases, 38 (95%) showed positive staining for PMab-52. In particular, 12 cases (30%) showed a strong membrane-staining pattern of squamous cell carcinoma cells. PMab-52 can be useful for antibody therapy against feline podoplanin-expressing squamous cell carcinomas.

  19. [Transitional cell carcinoma of the ovary. Morphological and clinical features].

    PubMed

    Kommoss, F; Kommoss, S; Eichhorn, J; Schmidt, D

    2007-05-01

    Transitional cell carcinoma of the ovary (TCC-O) is a less common type of malignant surface epithelial-stromal tumor of the ovary, still with uncertain incidence. Histologically, TCC-O resembles urothelial carcinoma of the urinary system, and by definition does not contain a Brenner tumor component. TCC-O may not be a bona fide urothelial neoplasm, however, but rather a lesion of the Müllerian type derived from the ovarian surface epithelium. This notion is supported by the existence of mixed tumors consisting of TCC-O and other histological types of ovarian carcinoma, as well as the observation that TCC-O has a Müllerian type but not a urothelial-like immunohistochemical profile. Besides metastatic urothelial carcinoma of the urinary tract, the other types of ovarian carcinoma, as well as sex cord-stromal tumors such as adult granulosa cell tumors, have to be considered in the differential diagnosis of TCC-O. A recent analysis of a large series of advanced ovarian carcinomas treated by radical surgery and postoperative chemotherapy confirms studies that had suggested that TCC-O has a better prognosis (with current treatment) than that of the other histological types of ovarian carcinoma. Further studies applying standardized histopathological criteria are needed to clarify the true incidence and behavior of TCC-O. In addition, it is important to study the biological and molecular background of this apparently less aggressive phenotype.

  20. Basal cell carcinoma vs basaloid squamous cell carcinoma of the skin: an immunohistochemical reappraisal.

    PubMed

    Webb, David V; Mentrikoski, Mark J; Verduin, Lindsey; Brill, Louis B; Wick, Mark R

    2015-04-01

    Typical cutaneous basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are morphologically dissimilar. It is well known, however, that poorly differentiated SCC may assume a basaloid phenotype, complicating the histologic distinction between these 2 neoplasms. Selected immunohistochemical stains have been used in the past to aid in that differential diagnosis. In the current study, additional markers were evaluated to determine whether they would be helpful in that regard. Twenty-nine cases of metatypical (squamoid) BCC (MBCC) and 25 examples of basaloid SCC (BSCC) were studied using the antibodies Ber-EP4 and MOC-31 as well as a plant lectin preparation from Ulex europaeus I (UEA-1). The resulting immunostains were interpreted independently by 3 pathologists, and the results showed that MBCCs demonstrated strong and diffuse staining for Ber-EP4 (25/29) and MOC-31 (29/29). In contrast, BSCCs tended to be only sporadically reactive for both markers (4/25 and 1/25 cases, respectively). Labeling for UEA-1 was observed in almost all BSCCs (24/25), but only 6 of 29 cases of MBCC showed limited, focal staining with that lectin. These data suggest that MOC-31 is a useful marker in the specified differential diagnosis, especially when used together with UEA-1. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. 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.

  2. Epithelial-to-mesenchymal transition in penile squamous cell carcinoma.

    PubMed

    Masferrer, Emili; Ferrándiz-Pulido, Carla; Masferrer-Niubò, Magalí; Rodríguez-Rodríguez, Alfredo; Gil, Inmaculada; Pont, Antoni; Servitje, Octavi; García de Herreros, Antonio; Lloveras, Belen; García-Patos, Vicenç; Pujol, Ramon M; Toll, Agustí; Hernández-Muñoz, Inmaculada

    2015-02-01

    Epithelial-to-mesenchymal transition is a phenomenon in epithelial tumors that involves loss of intercellular adhesion, mesenchymal phenotype acquisition and enhanced migratory potential. While the epithelial-to-mesenchymal transition process has been extensively linked to metastatic progression of squamous cell carcinoma, studies of the role of epithelial-to-mesenchymal transition in squamous cell carcinoma containing high risk human papillomaviruses are scarce. Moreover, to our knowledge epithelial-to-mesenchymal transition involvement in human penile squamous cell carcinoma, which can arise through transforming HPV infections or independently of HPV, has not been investigated. We evaluated the presence of epithelial-to-mesenchymal transition markers and their relationship to HPV in penile squamous cell carcinoma. We assessed the expression of E-cadherin, vimentin and the epithelial-to-mesenchymal transition related transcription factors Twist, Zeb1 and Snail by immunohistochemical staining in 64 penile squamous cell carcinoma cases. HPV was detected by polymerase chain reaction amplification. Simultaneous loss of membranous E-cadherin expression and vimentin over expression were noted in 43.5% of penile squamous cell carcinoma cases. HPV was significantly associated with loss of membranous E-cadherin but not with epithelial-to-mesenchymal transition. Recurrence and mortality rates were significantly higher in cases showing epithelial-to-mesenchymal transition. Our findings indicate that in penile squamous cell carcinoma epithelial-to-mesenchymal transition is associated with poor prognosis but not with the presence of HPV. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  3. [Exenteration of the Orbit for Basal Cell Carcinoma].

    PubMed

    Furdová, A; Horkovičová, K; Krčová, I; Krásnik, V

    2015-08-01

    Primary treatment of basal cell carcinoma of the lower eyelid and the inner corner is essentially surgical, but advanced lesions require extensive surgical interventions. In some cases it is necessary to continue with the mutilating surgery--exenteration of the orbit. In this work we evaluate the indications of radical solutions in patients with basal cell carcinoma invading the orbit and the subsequent possibility for individually made prosthesis to cover the defect of the cavity. Indications to exenteration of the orbit in patients with basal cell carcinoma findings in 2008-2013. Case report of 2 patients. In period 2008-20013 at the Dept. of Ophthalmology, Comenius University in Bratislava totally 221 patients with histologically confirmed basal cell carcinoma of the eyelids and the inner corner were treated. In 5 cases (2.7 %) with infiltration of the orbit the radical surgical procedure, exenteration was necessary. In 3 patients exenteration was indicated as the first surgical procedure in the treatment of basal cell carcinoma, since they had never visited ophthalmologist before only at in the stage of infiltration of the orbit (stage T4). In one case was indicated exenteration after previous surgical interventions and relapses. After healing the cavity patients got individually prepared epithesis. Surgical treatment of basal cell carcinoma involves the radical removal of the neoplasm entire eyelid and stage T1 or T2 can effectively cure virtually all tumors with satisfactory cosmetic and functional results. In advanced stages (T4 stage) by infiltrating the orbit by basal cell carcinoma exenteration of the orbit is necessary. This surgery is a serious situation for the patient and also for his relatives. Individually made prosthesis helps the patient to be enrolled to the social environment.

  4. 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.

  5. Primary intraosseous squamous cell carcinoma: a devil in disguise

    PubMed Central

    Pardhe, Nilesh; Bhagalia, Sanjay; Nayak, Prathibha Anand; Sireesha, Sundaragiri Krishna

    2013-01-01

    Primary intraosseous squamous cell carcinoma (PIOSCC) is a rare central jaw carcinoma derived from odontogenic epithelial remnants. When the tumour arises in an existing cyst, it may be difficult to recognise early PIOSCC and carry out necessary treatment. We report a case diagnosed in a 50-year-old man where timely intervention was delayed and prognosis was affected and the case diagnosed eventually by comprehensive clinical, radiological and histopathological examination. PMID:23749827

  6. Synchronous occurrence of neuroendocrine colon carcinoma and hairy cell leukemia.

    PubMed

    Salemis, Nikolaos S; Pinialidis, Dionisios; Tsiambas, Evangelos; Gakis, Christos; Nakos, Georgios; Sambaziotis, Dimitrios; Christofyllakis, Charalambos

    2011-09-01

    BACKGROUND-PURPOSE: The risk of secondary malignancy development in patients with hairy cell leukemia has been evaluated in several studies with varying results. The aim of this study is to describe a case of synchronous occurrence of neuroendocrine colon carcinoma and hairy cell leukemia. A 69-year-old man presented with rectal bleeding. Colonoscopy revealed a rectal tumor, whereas biopsy specimens revealed a poorly differentiated carcinoma. During the preoperative evaluation, pancytopenia was detected. At laparotomy, a mass was detected 16 cm from the anal verge and an anterior resection of the rectum was performed. Detailed histological and immunohistochemical analyses revealed a poorly differentiated neuroendocrine carcinoma of the rectum. Postoperative evaluation of pancytopenia revealed hairy cell leukemia. The patient was initially treated with chemotherapy for hairy cell leukemia followed by chemotherapy for neuroendocrine colon carcinoma. Survival was 44 months. To our knowledge, synchronous occurrence of neuroendocrine colon carcinoma and hairy cell leukemia has not been previously reported in the literature. Given the rare incidence of both entities in the general population, it is highly unlikely that they occurred together by chance. Further research is needed to determine what would be the optimal management options of patients with simultaneous hairy cell leukemia and a neuroendocrine colon cancer.

  7. Comparative transcriptional profiling of human Merkel cells and Merkel cell carcinoma.

    PubMed

    Mouchet, Nicolas; Coquart, Nolwenn; Lebonvallet, Nicolas; Le Gall-Ianotto, Christelle; Mogha, Ariane; Fautrel, Alain; Boulais, Nicholas; Dréno, Brigitte; Martin, Ludovic; Hu, Weiguo; Galibert, Marie-Dominique; Misery, Laurent

    2014-12-01

    Merkel cell carcinoma is believed to be derived from Merkel cells after infection by Merkel cell polyomavirus (MCPyV) and other poorly understood events. Transcriptional profiling using cDNA microarrays was performed on cells from MCPy-negative and MCPy-positive Merkel cell carcinomas and isolated normal Merkel cells. This microarray revealed numerous significantly upregulated genes and some downregulated genes. The extensive list of genes that were identified in these experiments provides a large body of potentially valuable information of Merkel cell carcinoma carcinogenesis and could represent a source of potential targets for cancer therapy. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Chemoprevention of esophageal squamous cell carcinoma

    SciTech Connect

    Stoner, Gary D.; Wang Lishu; Chen Tong

    2007-11-01

    Esophageal squamous cell carcinoma (SCC) is responsible for approximately one-sixth of all cancer-related mortality worldwide. This malignancy has a multifactorial etiology involving several environmental, dietary and genetic factors. Since esophageal cancer has often metastasized at the time of diagnosis, current treatment modalities offer poor survival and cure rates. Chemoprevention offers a viable alternative that could well be effective against the disease. Clinical investigations have shown that primary chemoprevention of this disease is feasible if potent inhibitory agents are identified. The Fischer 344 (F-344) rat model of esophageal SCC has been used extensively to investigate the biology of the disease, andmore » to identify chemopreventive agents that could be useful in human trials. Multiple compounds that inhibit tumor initiation by esophageal carcinogens have been identified using this model. These include several isothiocyanates, diallyl sulfide and polyphenolic compounds. These compounds influence the metabolic activation of esophageal carcinogens resulting in reduced genetic (DNA) damage. Recently, a few agents have been shown to inhibit the progression of preneoplastic lesions in the rat esophagus into tumors. These agents include inhibitors of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), vascular endothelial growth factor (VEGF) and c-Jun [a component of activator protein-1 (AP-1)]. Using a food-based approach to cancer prevention, we have shown that freeze-dried berry preparations inhibit both the initiation and promotion/progression stages of esophageal SCC in F-344 rats. These observations have led to a clinical trial in China to evaluate the ability of freeze-dried strawberries to influence the progression of esophageal dysplasia to SCC.« less

  9. Merkel Cell Carcinoma of Unknown Primary Origin

    PubMed Central

    Deneve, Jeremiah L.; Messina, Jane L.; Marzban, Suroosh S.; Gonzalez, Ricardo J.; Walls, Brooke M.; Fisher, Kate J.; Ann Chen, Y.; Wayne Cruse, C.; Sondak, Vernon K.; Zager, Jonathan S.

    2015-01-01

    Background Merkel cell carcinoma (MCC) is a rare neuroendocrine tumor of the skin. MCC from an unknown primary origin (MCCUP) can present a diagnostic and therapeutic challenge. We describe our single-institution experience with the diagnosis and management of MCCUP presenting as metastases to lymph nodes. Methods After institutional review board approval, our institutional database spanning the years 1998–2010 was queried for patients with MCCUP. Clinicopathologic variables and outcomes were assessed. Results From a database of 321 patients with MCC, 38 (12%) were identified as having nodal MCCUP. Median age was 67 years, and 79% were men. Nodal basins involved at presentation were cervical (58%), axillary/epitrochlear (21%), or inguinal/iliac (21%). CK20 staining was positive in 93% of tumors tested, and all were negative for thyroid transcription factor-1. Twenty-nine patients (76%) underwent complete regional lymph node dissection (LND): 3 had LND alone, ten had LND and adjuvant radiotherapy, and 16 underwent LND followed by chemoradiotherapy. Definitive chemoradiotherapy without surgery was provided to six patients (16%), while radiotherapy alone was provided to three (8%). Recurrence was observed in 34% of patients. Median recurrence-free survival was 35 months. Ten patients (26%) died, five of disease and five of other causes. The median overall survival was 104 months. Conclusions Nodal MCCUP is a rare disease affecting primarily elderly white men. Recurrence is observed in approximately one-third of patients, with a 104 month median overall survival after a multimodal treatment approach consisting of surgery along with adjuvant chemotherapy and radiotherapy in the majority of patients. PMID:22271206

  10. Intratumoral PV701 in Treating Patients With Advanced or Recurrent Unresectable Squamous Cell Carcinoma of the Head and Neck

    ClinicalTrials.gov

    2013-01-23

    Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Salivary Gland Squamous Cell Carcinoma; Stage III Salivary Gland Cancer; Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Nasopharynx; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage III Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IV Salivary Gland Cancer; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Larynx; Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IV Squamous Cell Carcinoma of the Oropharynx; Stage IV Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity

  11. [Glandular squamous cell carcinoma of the urinary bladder].

    PubMed

    Kovylina, M V; Pushkar', D Iu; Zaĭrat'iants, O V; Rasner, P I

    2006-01-01

    The paper gives a clinical observation of a 52 year-old male with a rare histological urinary bladder tumor primary grandular-squamous-cell carcinoma (pT3N IM0). The tumor is represented by two components large acinic-cell adenocarcinoma and squamous-cell carcinoma with keratinization, which smoothly pass one into another; the tumor has grown through all layers of the urinary bladder wall but it has failed to grow into the peritoneum. A microscopic study has indicated that the urachus is intact. Metastases were found in 3 of 8 lymph nodes: one showed high-grade adenocarcinoma and two others displayed average-grade squamous-cell carcinoma.

  12. [The factors involved in invasive ability of endometrial carcinoma cells].

    PubMed

    Mori, Y; Mizuuchi, H; Sato, K; Okamura, N; Kudo, R

    1994-06-01

    The in vitro invasive ability, the expression of cell adhesion molecule E-cadherin, activity of matrix metalloproteinase (MMP) and K-ras point mutation were investigated in eight human endometrial carcinoma cell lines. 1) In vitro invasive abilities of endometrial carcinoma cell lines depend on the degree of cell differentiation and the origin of cell lines. A poorly-differentiated carcinoma cell line (NUE-1) and a cell line derived from metastatic lymph node (SNG-M) were more invasive than moderately-(HEC-1A, HEC-1BE) and well-differentiated (HEC-6, Ishikawa) cell lines. 2) Immunohistochemically, less or non-invasive cell lines expressed E-cadherin strongly, whereas a highly invasive cell line (NUE-1) expressed E-cadherin weakly. 3) When cultured on Matrigel-coated dishes, the tumor cells derived from moderately- and well-differentiated carcinoma aggregated with each other and did not invade Matrigel in the invasion assay. The aggregated cells expressed E-cadherin more strongly when cultured on Matrigel. 4) 72-kD gelatinase (MMP-2) was secreted in serum-free conditioned medium of all cell lines. In an invasive cell line (NUE-1,SNG-M), the activity of MMP-2 was stronger than in other cell lines. And the activity of 92-kDa gelatinase (MMP-9) was detected in most invasive cell line (NUE-1). 5) Point mutation of K-ras codon 12 was detected in four of eight (50%) cell lines by the PCR-RFLP method. The changes in the DNA sequence were identified, but K-ras point mutation was not correlated with in vitro invasiveness of the tumor cells.

  13. Onalespib in Treating Patients With Locoregionally Advanced Squamous Cell Carcinoma of the Head and Neck Receiving Radiation Therapy and Cisplatin

    ClinicalTrials.gov

    2018-04-23

    Stage III Hypopharyngeal Squamous Cell Carcinoma AJCC v7; Stage III Laryngeal Squamous Cell Carcinoma AJCC v6 and v7; Stage III Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage III Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Hypopharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Laryngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVA Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Hypopharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Laryngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVB Oropharyngeal Squamous Cell Carcinoma AJCC v7

  14. [Merkel cell carcinoma experience in a reference medical center.

    PubMed

    Roesch-Dietlen, Federico; Devezé-Bocardi, Raúl; Ruiz-Juárez, Isabel; Grube-Pagola, Peter; Romero-Sierra, Graciela; Remes-Troche, José María; Silva-Cañetas, Carmen Sofía; Lozoya-López Escalera, Hilda

    2013-01-01

    Background: Merkel cell carcinoma is a rare tumor that occurs on areas exposed to ultraviolet light. It is usually asymptomatic and it is diagnosed late often. The treatment is surgical, associated with adjuvant radiotherapy. The objective was to present the experience in the management of Merkel cell carcinoma in a reference medical center. Methods: all patients with Merkel cell carcinoma treated at the Instituto de Investigaciones Médico-Biológicas of the Universidad Veracruzana during the period 2008 to 2011 were studied. Sex, age, evolution time, tumor localization, size, metastases and treatment were analyzed. Results: of 3217 patients treated, three cases were Merkel cell carcinoma (0.09 %), their age was 52.1 ± 14.17, male predominance of 66.67 %; the evolution time was of 29.66 ± 35.36 months; the tumour localization was on inguinal region, anterior chest and left arm; the noodle size was of 6.0 ± 5.19 cm; two patients had lymph node metastases. In two cases, resection and lymphadenectomy were performed. They all received radiation therapy and chemotherapy in one case. Histologically the medium variant predominated; immunohistochemistry was positive in the three cases. One patient died ten months after the study was done. Conclusions: our experience is similar with others authors, Merkel cell carcinoma is a rare tumor, usually diagnosed late, and it has poor survival.

  15. OVARIAN HILUS CELLS AND ENDOMETRIAL CARCINOMA WITH REFERENCE TO RADIATION

    SciTech Connect

    Ames, S.; Janovski, N.A.

    1963-07-01

    A survey of the relation of hilus cell genesis and frequency of detection in ovaries to adenocarcinoma of the endometrium is presented. Results were based on the examination of 281 ovaries obtained from patients with endometrial carcinoma. The results showed that there was no statistical difference between the occurrence of hilus cells in the endometrial carcinoma group and a control group (33 and 25% respectively). However, if mode of treatment was taken into consideration, and patients undergoing irradiation for endometrial adenocarcinoma prior to operation separated into an individual group, there was a significant difference in the distribution of hilus cellsmore » in those patients as compared with the nonirradiated carcinoma group, at the level of 5%. The radiotherapy in these cases consisisted mainly of 50100 mg intracavitary Ra for approximates 72 hr. A surprisingly high incidence (60%) of ovarian hilus cells was found in patients who underwent radioinduced menopause for benign gynecologic conditions prior to developing adenocarcinoma of the endometrium. The incidence in all postmenopausal patients was only 37%. Ovarian hilus cells were more prevalent in postmenopausal women irrespective of endometrial carcinoma. Premenopausal women with endometrial carcinoma who received no irradiation prior to definitive operation are, therefore, the ideal subjects for further investigation of the relation between endometrial adenocarcinoma and ovarian hilus cells. (BBB)« less

  16. Human papilloma virus prevalence in laryngeal squamous cell carcinoma.

    PubMed

    Gungor, A; Cincik, H; Baloglu, H; Cekin, E; Dogru, S; Dursun, E

    2007-08-01

    To determine the prevalence and type of human papilloma virus deoxyribonucleic acid (DNA) in cases of laryngeal squamous cell carcinoma. We analysed the prevalence of human papilloma virus infection in archived paraffin block specimens taken from 99 cases of laryngeal squamous cell carcinoma between 1990 and 2005, using polymerase chain reaction techniques. Biopsy specimens from five proven verrucous skin lesions were used as positive controls, and peripheral blood samples from five healthy volunteers were used as negative controls. Four test samples were found to have inadequate deoxyribonucleic acid purity and were therefore excluded from the study. Human papilloma virus deoxyribonucleic acid was detected in seven of 95 cases of laryngeal squamous cell carcinoma (7.36 per cent). Human papilloma virus genotyping revealed double human papilloma virus infection in three cases and single human papilloma virus infection in the remaining four cases. The human papilloma virus genotypes detected were 6, 11 and 16 (the latter detected in only one case). In our series, a very low human papilloma virus prevalence was found among laryngeal squamous cell carcinoma cases. The human papilloma virus genotypes detected were mostly 6 and/or 11, and 16 in only one case. To the best of our knowledge, this is the first report of human papilloma virus prevalence in laryngeal squamous cell carcinoma, based on polymerase chain reaction genotyping in a Turkish population.

  17. Targeted mutation analysis of endometrial clear cell carcinoma.

    PubMed

    Hoang, Lien N; McConechy, Melissa K; Meng, Bo; McIntyre, John B; Ewanowich, Carol; Gilks, Cyril Blake; Huntsman, David G; Köbel, Martin; Lee, Cheng-Han

    2015-04-01

    Endometrial clear cell carcinomas (CCC) constitute fewer than 5% of all carcinomas of the endometrium. Currently, little is known regarding the genetic basis of endometrial CCC. We performed genomic and immunohistochemical analyses on 14 rigorously reviewed pure endometrial CCC. The genomic analysis consisted of sequencing the coding regions of 26 genes implicated previously in endometrial carcinoma. Twelve of 14 tumours displayed a prototypical CCC immunophenotype [napsin A+, hepatocyte nuclear factor-1β (HNF1β(+) ) and oestrogen receptor(-) ] and all showed intact mismatch repair protein expression. We detected mutations in 11 of 14 tumours, and there was a predominance of mutations involving genes that are mutated more frequently in endometrial serous carcinomas than in endometrioid carcinomas. Two tumours displayed a prototypical serous carcinoma mutation profile (concurrent TP53 and PPP2R1A mutations, without PTEN, CTNNB1 or ARID1A mutation). No mutations in PTEN, CTNNB1 or POLE were identified. The overall mutation profile of this cohort of endometrial CCC appears to be more serous-like than endometrioid-like, with a minor subset in the TP53-mutated CCC showing serous carcinoma profile. These findings provide new insights into the molecular features of morphologically prototypical endometrial CCC, and underscore the need for further investigations into the oncogenesis of endometrial CCC. © 2014 John Wiley & Sons Ltd.

  18. Spindle cell carcinoma of the esophagus

    PubMed Central

    Zhang, Baihua; Xiao, Qin; Yang, Desong; Li, Xu; Hu, Jun; Wang, Yonggang; Wang, Wenxiang

    2016-01-01

    Abstract This study conducted a retrospective multicenter analysis to investigate the clinicopathological features, optimal therapeutic strategy, and prognosis of spindle cell carcinoma (SpCC) of the esophagus. A total of 71 patients with esophageal SpCC from 3 large cancer centers in China were systematically analyzed. All patients received curative resection, 13 patients received adjuvant radiotherapy and 15 patients received adjuvant combination chemotherapy. Additionally, a total of 1852 patients with typical esophageal SCC (SCC) were selected as controls in this study. SpCC mostly presented as a polypoid appearance (66.2%), and the surrounding mucosa showed high-grade hyperplasia or superficial SCC in 31 cases (43.7%). Two patients even had extensive carcinoma in situ that spread to the resection margins. Patients in the SpCC group were more likely to present with stage I lesions compared with those in the typical SCC group (33.8% vs 8.0%, P < 0.001). Although the percentage of T1/2 lesions was higher in the SpCC group than in the typical SCC group (67.6% vs 29.7%, P < 0.001), both groups had similar rates of locoregional lymphatic metastases (45.1% vs 48.4%, P = 0.578). The median survival time and 5-year overall survival of the SpCC group was 43 months and 44.8%, respectively, higher than 37.5 months and 38.3%, respectively, for the typical SCC group (P = 0.044). In univariate analysis, the macroscopical type and pathological T, N, and TNM stages had a statistically significant impact on the prognosis of SpCC after curative resection. However, only the TNM stage (hazard ratio, 2.708; 95% confidence interval, 1.786–4.105, P < 0.001) was identified as an independent prognostic factor in multivariate analysis. The 5-year OS of SpCC in stages I (79.8%) and II (39.7%) were significantly longer than that of stages III/IV (16.2%) (P < 0.001 and P = 0.012). As those SpCC cases that received chemoradiotherapy were in more advanced stages

  19. A Phase I Study of LJM716 in Squamous Cell Carcinoma of Head and Neck, or HER2+ Breast Cancer or Gastric Cancer

    ClinicalTrials.gov

    2014-04-21

    HER2 + Breast Cancer, HER2 + Gastric Cancer, Squamous Cell Carcinoma of Head and Neck, Esophageal Squamous Cell Carcinoma; HER2 + Breast Cancer; HER2 + Gastric Cancer; Squamous Cell Carcinoma of Head and Neck; Esophageal Squamous Cell Carcinoma

  20. Neuroendocrine small cell carcinoma of the uterine cervix.

    PubMed

    Reig Castillejo, Anna; Membrive Conejo, Ismael; Foro Arnalot, Palmira; Rodríguez de Dios, Nuria; Algara López, Manuel

    2010-07-01

    Neuroendocrine small cell carcinoma of the uterine cervix (SCC) is a rare disease that mixes clinical and biological characteristics of both cervical neoplasms and neuroendocrine small cell cancer. The prognosis is poor and the optimal treatment has not yet been clarified. Multimodality treatment, with surgery and concurrent chemoradiation has recently been shown to improve local control and survival rates.

  1. Fusion with stem cell makes the hepatocellular carcinoma cells similar to liver tumor-initiating cells.

    PubMed

    Wang, Ran; Chen, Shuxun; Li, Changxian; Ng, Kevin Tak Pan; Kong, Chi-wing; Cheng, Jinping; Cheng, Shuk Han; Li, Ronald A; Lo, Chung Mau; Man, Kwan; Sun, Dong

    2016-02-04

    Cell fusion is a fast and highly efficient technique for cells to acquire new properties. The fusion of somatic cells with stem cells can reprogram somatic cells to a pluripotent state. Our research on the fusion of stem cells and cancer cells demonstrates that the fused cells can exhibit stemness and cancer cell-like characteristics. Thus, tumor-initiating cell-like cells are generated. We employed laser-induced single-cell fusion technique to fuse the hepatocellular carcinoma cells and human embryonic stem cells (hESC). Real-time RT-PCR, flow cytometry and in vivo tumorigenicity assay were adopted to identify the gene expression difference. We successfully produced a fused cell line that coalesces the gene expression information of hepatocellular carcinoma cells and stem cells. Experimental results showed that the fused cells expressed cancer and stemness markers as well as exhibited increased resistance to drug treatment and enhanced tumorigenesis. Fusion with stem cells transforms liver cancer cells into tumor initiating-like cells. Results indicate that fusion between cancer cell and stem cell may generate tumor initiating-like cells.

  2. Tropomyosin Receptor Kinase A Expression on Merkel Cell Carcinoma Cells.

    PubMed

    Wehkamp, Ulrike; Stern, Sophie; Krüger, Sandra; Hauschild, Axel; Röcken, Christoph; Egberts, Friederike

    2017-11-01

    Merkel cell carcinoma (MCC) is a malignant neuroendocrine skin tumor frequently associated with the Merkel cell polyomavirus. Immune checkpoint therapy showed remarkable results, although not all patients are responsive to this therapy. Anti-tropomyosin receptor kinase A (TrkA)-targeted treatment has shown promising results in several tumor entities. To determine TrkA expression in MCC as a rationale for potential targeted therapy. This case series study investigated the MCC specimens of 55 patients treated at the Department of Dermatology, University Hospital of Schleswig-Holstein, Kiel, Germany, from January 1, 2005, through December 31, 2015. Thirty-nine of the 55 samples were suitable for further histopathologic examination. Expression of TrkA was explored by immunohistochemical analysis. Diagnosis of MCC was confirmed by staining positive for cytokeratin 20 (CK20) and synaptophysin. Expression of TrkA on the tumor cells. Specimens of 39 patients (21 women and 18 men; mean [SD] age, 75.0 [7.8] years) underwent immunohistochemical investigation. Thirty-eight of 38 specimens expressed CK20 and synaptophysin on the MCC tumor cells (100% expression). Merkel cell polyomavirus was detected in 32 of 38 specimens (84%). Tropomyosin receptor kinase A was found in all 36 evaluable specimens on the tumor cells; 34 (94%) showed a weak and 2 (6%) showed a strong cytoplasmic expression. In addition, strongly positive perinuclear dots were observed in 30 of 36 specimens (83%). Tropomyosin receptor kinase A was expressed on MCC tumor cells in 100% of evaluable specimens. This result may lead to the exploration of new targeted treatment options in MCC, especially for patients who do not respond to anti-programmed cell death protein 1 treatment.

  3. PKI 166 induced redox signalling and apoptosis through activation of p53, MAP kinase and caspase pathway in epidermoid carcinoma.

    PubMed

    Das, Subhasis; Dey, Kaushik Kumar; Bharti, Rashmi; MaitiChoudhury, Sujata; Maiti, Sukumar; Mandal, Mahitosh

    2012-01-01

    Cellular redox changes have emerged as a pivotal and proximal event in cancer. PKI 166 is used to determine the effects of redox sensitive inhibition of EGFR, metastasis and apoptosis in epidermoid carcinoma. Cytotoxicity study of PKI 166 (IC50 1.0 microM) treated A431 cells were performed by MTT assay for 48 and 72 hrs. Morphological analysis of PKI 166 treated A431 cells for 48 hrs. revealed the cell shrinkage, loss of filopodia and lamellipodia by phase contrast and SEM images in dose dependent manner. It has cytotoxic effects through inhibiting cellular proliferation, leads to the induction of apoptosis, as increased fraction of sub-G1 phase of the cell cycle, chromatin condensation and DNA ladder. It inhibited cyclin-D1 and cyclin-E expression and induced p53, p21 expression in dose dependent manner. Consequently, an imbalance of Bax/Bcl-2 ratio triggered caspase cascade and subsequent cleavage of PARP, thereby shifting the balance in favour of apoptosis. PKI 166 treatment actively stimulated reactive oxygen species (ROS) and mitochondrial membrane depolarization. It inhibited some metastatic properties of A431 cells supressing colony formation by soft agar assay and inhibition of MMP 9 activity by gelatin zymography and western blot analysis. PKI 166 inhibited growth factor induced phosphorylation of EGFR, Akt, MAPK, JNK and colony formation in A431 cells. Thus the inhibition of proliferation was associated with redox regulation of the caspase cascade, EGFR, Akt/PI3K, MAPK/ ERK and JNK pathway. On the other hand, increased antioxidant activity leads to decreased ROS generation inhibit the anti-proliferative and apoptotic properties of PKI 166 in A431 cells. These observations indicated PKI 166 induced redox signalling dependent inhibition of cell proliferation, metastatic properties and induction of apoptotic potential in epidermoid carcinoma.

  4. 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.

  5. Verrucoid Variant of Invasive Squamous Cell Carcinoma in Oral Submucous Fibrosis: A Clinicopathological Challenge.

    PubMed

    Ramani, Priya; Krithika, C; Ananthalakshmi, R; Singaram, Mamta; Jagdish, Praveena; Janardhanan, Sunitha; Jeevakarunyam, Sathiyajeeva

    2016-11-04

    Verrucous carcinoma (VC) is an exophytic, low-grade, well-differentiated variant of squamous cell carcinoma. It is described as a lesion appearing in the sixth or seventh decade of life that has minimal aggressive potential and, in long-standing cases, has been shown to transform into squamous cell carcinoma. Oral submucous fibrosis (OSMF) is a potentially malignant disorder, and about one-third of the affected population develop oral squamous cell carcinoma. The histopathological diagnosis of verrucous carcinoma is challenging, and the interpretation of early squamous cell carcinoma requires immense experience. Here we present a rare case of a 24-year-old male with OSMF transforming to verrucous carcinoma with invasive squamous cell carcinoma. Even though the case had a straightforward clinical diagnosis, the serial sectioning done for pathological diagnosis disclosed the squamous cell carcinoma.

  6. 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

  7. [High dosage therapy with stem cell transplantation in neuroendocrine carcinoma].

    PubMed

    Buxhofer, V; Ruckser, R; Kier, P; Habertheuer, K H; Zelenka, P; Tatzreiter, G; Dorner, S; Vedovelli, H; Sebesta, C; Hinterberger, W

    2000-01-01

    Neuroendocrine carcinoma and small-cell lung cancer (SCLC) are highly responsive to chemo- and radiotherapy. Nevertheless, most patients (pts.) experience relapse. At the 2nd department of medicine in the Donauspital, 4 pts. with neuroendocrine carcinomas of different primary sites underwent high-dose chemotherapy with autologous stem-cell transplantation (ASTx). Pt. 1 suffered from neuroendocrine lung cancer, pt. 2 from a small-cell carcinoma of the pancreas. Pt. 3 had a metastatic small-cell abdominal bulky tumor and pt. 4 presented with neuroendocrine carcinoma of the prostate. After 4-6 cycles induction chemotherapy pts. were consolidated with 1 cycle of HDCht and ASTx. Prior to HDCht pt. 1 and pt. 2 were in complete remission (CR) and pt. 3 and pt. 4 in partial remission. Pt. 3 converted in CR after HDCht. He is still in CR with a disease-free survival of 23 month after ASTx and 30 month after diagnosis. Pt. 1, 2 and 4 died from relapse 10, 16 and 5 month after ASTx and 16, 22 and 9 month after diagnosis. Pts. with neuroendocrine carcinomas might be suitable candidates for HDCht and ASTx.

  8. [c-MET Oncogene in Renal Cell Carcinomas].

    PubMed

    Erlmeier, F; Weichert, W; Autenrieth, M; Ivanyi, P; Hartmann, A; Steffens, S

    2016-12-01

    c-Met plays a significant role in multiple cellular processes. Being encoded by a proto-oncogene, tyrosine kinase supports aggressive tumour behaviour such as tumour invasiveness and formation of metastases. For some subtypes of renal cell carcinoma studies have shown a association between c-Met expression and clinical outcome or prognosis. Therefore, c-Met represents a prognostic marker in renal cell carcinoma.Furthermore, c-MET will play a decisive role as a possible target for targeted therapies in the era of personalised medicine. Especially for RCC, the dual inhibition of VEGF and c-MET tyrosine kinase in cases of metastatic, treatment-resistant tumours is gaining clinical relevance. The role of c-Met has not been fully elucidated for all subtypes of renal cell carcinomas. The relevance of c-Met for the remaining subtypes of renal tumours has yet to be clarified. © Georg Thieme Verlag KG Stuttgart · New York.

  9. Avelumab for the treatment of metastatic Merkel cell carcinoma.

    PubMed

    Cordes, L M; Gulley, J L

    2017-07-01

    Avelumab is a promising new therapeutic agent for patients with metastatic Merkel cell carcinoma, a rare and aggressive type of neuroendocrine tumor of the skin. Until the recent approval of avelumab (Bavencio), no therapies were approved by the U.S. Food and Drug Administration for the treatment of metastatic Merkel cell carcinoma. In a recent trial, avelumab, an anti-programmed death ligand-1 antibody, demonstrated an objective response in 28 of 88 patients (31.8% [95.9% CI, 21.9-43.1]) with advanced, chemotherapy-refractory Merkel cell carcinoma. Overall, avelumab was well tolerated at a dose of 10 mg/kg administered intravenously every 2 weeks. Serious treatment-related adverse events were reported in 5 patients (6%), but no grade 4 adverse events or treatment-related deaths were reported. Preliminary data evaluating avelumab in chemotherapy-naive patients is also encouraging. Copyright 2017 Clarivate Analytics.

  10. Clear Cell Carcinoma of the Penis: An HPV-related Variant of Squamous Cell Carcinoma: A Report of 3 Cases.

    PubMed

    Sanchez, Diego F; Rodriguez, Ingrid M; Piris, Adriano; Cañete, Sofía; Lezcano, Cecilia; Velazquez, Elsa F; Fernandez-Nestosa, Maria J; Mendez-Pena, Javier E; Hoang, Mai P; Cubilla, Antonio L

    2016-07-01

    Penile clear cell carcinoma originating in skin adnexal glands has been previously reported. Here, we present 3 morphologically distinctive penile tumors with prominent clear cell features originating not in the penile skin but in the mucosal tissues of the glans surface squamous epithelium. Clinical and pathologic features were evaluated. Immunohistochemical stains were GATA3 and p16. Human papilloma virus (HPV) detection by in situ hybridization was performed in 3 cases, and whole-tissue section-polymerase chain reaction was performed in 1 case. Patients' ages were 52, 88, and 95 years. Tumors were large and involved the glans and coronal sulcus in all cases. Microscopically, nonkeratinizing clear cells predominated. Growth was in solid nests with comedo-like or geographic necrosis. Focal areas of invasive warty or basaloid carcinomas showing in addition warty or basaloid penile intraepithelial neoplasia were present in 2 cases. There was invasion of corpora cavernosa, lymphatic vessels, veins, and perineural spaces in all cases. p16 was positive, and GATA3 stain was negative in the 3 cases. HPV was detected in 3 cases by in situ hybridization and in 1 case by polymerase chain reaction. Differential diagnoses included other HPV-related penile carcinomas, skin adnexal tumors, and metastatic renal cell carcinoma. Features that support primary penile carcinoma were tumor location, concomitant warty and/or basaloid penile intraepithelial neoplasia, and HPV positivity. Clinical groin metastases were present in all cases, pathologically confirmed in 1. Two patients died from tumor dissemination at 9 and 12 months after penectomy. Clear cell carcinoma, another morphologic variant related to HPV, originates in the penile mucosal surface and is probably related to warty carcinomas.

  11. Sunitinib, Cetuximab, and Radiation Therapy in Treating Patients With Locally Advanced or Recurrent Squamous Cell Carcinoma of the Head and Neck

    ClinicalTrials.gov

    2013-07-01

    Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Salivary Gland Squamous Cell Carcinoma; Stage III Salivary Gland Cancer; Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Nasopharynx; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage III Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage III Verrucous Carcinoma of the Larynx; Stage III Verrucous Carcinoma of the Oral Cavity; Stage IV Salivary Gland Cancer; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Larynx; Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IV Squamous Cell Carcinoma of the Oropharynx; Stage IV Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IV Verrucous Carcinoma of the Larynx; Stage IV Verrucous Carcinoma of the Oral Cavity; Tongue Cancer; Untreated Metastatic Squamous Neck Cancer With Occult Primary

  12. Sclerodermiform basal cell carcinoma: how much can we rely on dermatoscopy to differentiate from non-aggressive basal cell carcinomas? Analysis of 1256 cases.

    PubMed

    Husein-ElAhmed, Husein

    2018-03-01

    The behaviour of each basal cell carcinoma is known to be different according to the histological growth pattern. Among these aggressive lesions, sclerodermiform basal cell carcinomas are the most common type. This is a challenging-to-treat lesion due to its deep tissue invasion, rapid growth, risk of metastasis and overall poor prognosis if not diagnosed in early stages. To investigate if sclerodermiform basal cell carcinomas are diagnosed later compared to non-sclerodermiform basal cell carcinoma Method: All lesions excised from 2000 to 2010 were included. A pathologist classified the lesions in two cohorts: one with specimens of non-aggressive basal cell carcinoma (superficial, nodular and pigmented), and other with sclerodermiform basal cell carcinoma. For each lesion, we collected patient's information from digital medical records regarding: gender, age when first attending the clinic and the tumor location. 1256 lesions were included, out of which 296 (23.6%) corresponded to sclerodermiform basal cell carcinoma, whereas 960 (76.4%) were non-aggressive subtypes of basal cell carcinoma. The age of diagnosis was: 72.78±12.31 years for sclerodermiform basal cell and 69.26±13.87 years for non-aggressive basal cell carcinoma (P<.0001). Sclerodermiform basal cell carcinomas are diagnosed on average 3.52 years later than non-aggressive basal cell carcinomas. Sclerodermiform basal cell carcinomas were diagnosed 3.40 years and 2.34 years later than non-aggressive basal cell carcinomas in younger and older patients respectively (P=.002 and P=.03, respectively). retrospective design. The diagnostic accuracy and primary clinic conjecture of sclerodermiform basal cell carcinomas is quite low compared to other forms of basal cell carcinoma such as nodular, superficial and pigmented. The dermoscopic vascular patterns, which is the basis for the diagnosis of non-melanocytic nonpigmented skin tumors, may not be particularly useful in identifying sclerodermiform basal cell

  13. Identification of the zinc finger 216 (ZNF216) in human carcinoma cells: a potential regulator of EGFR activity

    PubMed Central

    Mincione, Gabriella; Di Marcantonio, Maria Carmela; Tarantelli, Chiara; Savino, Luca; Ponti, Donatella; Marchisio, Marco; Lanuti, Paola; Sancilio, Silvia; Calogero, Antonella; Di Pietro, Roberta; Muraro, Raffaella

    2016-01-01

    Epidermal Growth Factor Receptor (EGFR), a member of the ErbB family of receptor tyrosine kinase (RTK) proteins, is aberrantly expressed or deregulated in tumors and plays pivotal roles in cancer onset and metastatic progression. ZNF216 gene has been identified as one of Immediate Early Genes (IEGs) induced by RTKs. Overexpression of ZNF216 protein sensitizes 293 cell line to TNF-α induced apoptosis. However, ZNF216 overexpression has been reported in medulloblastomas and metastatic nasopharyngeal carcinomas. Thus, the role of this protein is still not clearly understood. In this study, the inverse correlation between EGFR and ZNF216 expression was confirmed in various human cancer cell lines differently expressing EGFR. EGF treatment of NIH3T3 cells overexpressing both EGFR and ZNF216 (NIH3T3-EGFR/ZNF216), induced a long lasting activation of EGFR in the cytosolic fraction and an accumulation of phosphorylated EGFR (pEGFR) more in the nuclear than in the cytosolic fraction compared to NIH3T3-EGFR cells. Moreover, EGF was able to stimulate an increased expression of ZNF216 in the cytosolic compartment and its nuclear translocation in a time-dependent manner in NIH3T3-EGFR/ZNF216. A similar trend was observed in A431 cells endogenously expressing the EGFR and transfected with Znf216. The increased levels of pEGFR and ZNF216 in the nuclear fraction of NIH3T3-EGFR/ZNF216 cells were paralleled by increased levels of phospho-MAPK and phospho-Akt. Surprisingly, EGF treatment of NIH3T3-EGFR/ZNF216 cells induced a significant increase of apoptosis thus indicating that ZNF216 could sensitize cells to EGF-induced apoptosis and suggesting that it may be involved in the regulation and effects of EGFR signaling. PMID:27732953

  14. Cell adhesion molecules, the extracellular matrix and oral squamous carcinoma.

    PubMed

    Lyons, A J; Jones, J

    2007-08-01

    Carcinomas are characterized by invasion of malignant cells into the underlying connective tissue and migration of malignant cells to form metastases at distant sites. These processes require alterations in cell-cell and cell-extracellular matrix interactions. As cell adhesion molecules play a role in cell-cell and cell-extracellular matrix adhesion and interactions they are involved in the process of tumour invasion and metastases. In epithelial tissues, receptors of the integrin family mediate adhesion to the adjacent matrix whereas cadherins largely mediate intercellular adhesion. These and other cell adhesion molecules such as intercellular adhesion molecule-1, CD44, dystroglycans and selectins, are involved and undergo changes in carcinomas, which provide possible targets for anti-cancer drug treatments. In the extracellular matrix that is associated with tumours, laminin 5, oncofetal fibronectin and tenascin C appear. The degree of expression of some of these moieties indicates prognosis in oral cancer and offer targets for antibody-directed radiotherapy. Metalloproteases which degrade the extracellular matrix are increased in carcinomas, and their activity is necessary for tumour angiogenesis and consequent invasion and metastases. Metalloprotease inhibitors have begun to produce decreases in mortality in clinical trials. This report provides a brief overview of our current understanding of cell adhesion molecules, the extracellular matrix, tumour invasion and metastasis.

  15. Nesfatin-1 inhibits ovarian epithelial carcinoma cell proliferation in vitro

    SciTech Connect

    Xu, Yang; Pang, Xiaoyan; Dong, Mei

    Highlights: •Nesfatin-1 inhibits the proliferation and growth of HO-8910 cells by G1 phase arrest. •Nesfatin-1 enhances HO-8910 cell apoptosis. •Nesfatin-1 inhibits HO-8910 cell proliferation via mTOR and RhoA/ROCK signaling pathway. •The first report of nesfatin-1-mediated proliferation in ovarian epithelial carcinoma. -- Abstract: Nesfatin-1, an 82-amino-acid peptide derived from a 396-amino-acid precursor protein nucleobindin 2 (NUCB2), was originally identified in hypothalamic nuclei involved in the regulation of food intake. It was recently reported that nesfatin-1 is a novel depot specific adipokine preferentially produced by subcutaneous tissue, with obesity- and food deprivation-regulated expression. Although a relation between ovarian cancer mortality and obesitymore » has been previously established, a role of nesfatin-1 in ovarian epithelial carcinoma remains unknown. The aim of the present study is to examine the effect of nesfatin-1 on ovary carcinoma cells proliferation. We found that nesfatin-1 inhibits the proliferation and growth of HO-8910 cells by G1 phase arrest, this inhibition could be abolished by nesfatin-1 neutralizing antibody. Nesfatin-1 enhances HO-8910 cell apoptosis, activation of mammalian target of rapamycin (mTOR) and RhoA/ROCK signaling pathway block the effects of nesfatin-1-induced apoptosis, therefore reverses the inhibition of HO-8910 cell proliferation by nesfatin-1. In conclusion, the present study demonstrated that nesfatin-1 can inhibit the proliferation in human ovarian epithelial carcinoma cell line HO-8910 cells through inducing apoptosis via mTOR and RhoA/ROCK signaling pathway. This study provides a novel regulatory signaling pathway of nesfatin-1-regulated ovarian epithelial carcinoma growth and may contribute to ovarian cancer prevention and therapy, especially in obese patients.« less

  16. Basal Cell Carcinoma: A Patient and Physician's Experience.

    PubMed

    Cohen, Barbara J; Cohen, Eliahou S; Cohen, Philip R

    2018-06-02

    In this article, the first coauthor, a patient with a basal cell carcinoma on her upper lip, discusses her experience with Mohs micrographic surgery for the treatment of the skin cancer. The second coauthor, who is the patient's physician (a dermatologist who shares her last name but is not a relative), diagnosed her skin cancer and referred her for Mohs surgery. The third coauthor, who is the patient's son and not only a dermatologist, but also a dermatopathologist and a Mohs surgeon (and also shares her last name), summarizes the presentation and treatment of the basal cell carcinoma.

  17. Squamous cell carcinoma in exstrophy of the bladder.

    PubMed

    Sharma, Pramod Kumar; Pandey, Praveen Kumar; Vijay, Mukesh Kumar; Bera, Malay Kumar; Singh, Jitendra Pratap; Saha, Kaushik

    2013-08-01

    Exstrophy of the bladder is a rare congenital anomaly with an incidence of about 1 per 50,000 newborns. The malignant potential of the exstrophied bladder mucosa is well known; 95% are adenocarcinomas, and 3% to 5% are squamous cell carcinomas. Most of the malignant tumors (60%) associated with an exstrophy of the bladder occur during the fourth and fifth decades of life. Of the remaining, about 20% each occur after 60 years and before 40 years. Here we present a case in which squamous cell carcinoma developed in an unrepaired exstrophy of the bladder. We present the management of the case and a brief review of the literature.

  18. Squamous Cell Carcinoma in Exstrophy of the Bladder

    PubMed Central

    Pandey, Praveen Kumar; Vijay, Mukesh Kumar; Bera, Malay Kumar; Singh, Jitendra Pratap; Saha, Kaushik

    2013-01-01

    Exstrophy of the bladder is a rare congenital anomaly with an incidence of about 1 per 50,000 newborns. The malignant potential of the exstrophied bladder mucosa is well known; 95% are adenocarcinomas, and 3% to 5% are squamous cell carcinomas. Most of the malignant tumors (60%) associated with an exstrophy of the bladder occur during the fourth and fifth decades of life. Of the remaining, about 20% each occur after 60 years and before 40 years. Here we present a case in which squamous cell carcinoma developed in an unrepaired exstrophy of the bladder. We present the management of the case and a brief review of the literature. PMID:23956833

  19. Paracoccidioidomycosis: report of 2 cases mimicking squamous cell carcinoma.

    PubMed

    Meneses-García, Abelardo; Mosqueda-Taylor, Adalberto; Morales-de la Luz, Rosario; Rivera, Luz María Ruíz-Godoy

    2002-11-01

    Paracoccidioidomycosis is an endemic fungal infection in Latin America. This mucocutaneous disease often involves the oral mucosa and may clinically resemble other infectious and neoplastic processes. Paracoccidioidomycosis that clinically suggested squamous cell carcinoma was diagnosed in 2 patients with a history of heavy alcohol and tobacco use. Antifungal therapy with ketoconazole and itraconazole resulted in resolution of the oral lesions. Interestingly, 1 patient had a pulmonary lesion that persisted after antifungal therapy, and biopsy proved this to be a squamous cell carcinoma of the lung.

  20. 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.

  1. Basal cell carcinomas in elderly patients treated by cryotherapy

    PubMed Central

    Chiriac, Anca; Mihaila, Doina; Foia, Liliana; Solovan, Caius

    2013-01-01

    Basal cell carcinoma is a malignant skin tumor with high incidence in our country, especially in rural areas, on sun-exposed skin (particularly on the face) in elderly patients. We present three cases of basal cell carcinoma with good results with cryotherapy. This report aims to outline and to prove that in some difficult situations, a simple, inexpensive, easy-to-perform procedure with no contraindications and with minimal side effects (erythema, mild pain) can be applied and resolve such cases. PMID:23569366

  2. Hürthle cell carcinoma in a lingual thyroid.

    PubMed

    Thakur, Jagdeep; Verma, Naina; Singh, Riya

    2018-06-13

    To present a case of lingual thyroid Hürthle cell carcinoma. A 37-year old female presented with dysphagia and recurrent haemorrhage. Histopathology was suggestive of Hürthle cell carcinoma; the tumour was excised by the transglossal approach which provided adequate exposure and helped avoid external scar or mandibular osteoetomy. Histopathology showed tumour-positive right lateral resection margin. This prompted referral to nuclear medicine for radioablation. Lingual thyroid cases should be followed up closely and fine needle aspiration biopsy should be considered when in doubt. ©2018The Author(s). Published by S. Karger AG, Basel.

  3. Acinic cell carcinoma in an African pygmy hedgehog (Atelerix albiventris).

    PubMed

    Fukuzawa, Ryuji; Fukuzawa, Kazuhiro; Abe, Hitoshi; Nagai, Toshihiro; Kameyama, Kaori

    2004-01-01

    A male African pygmy hedgehog (Atelerix albiventris), estimated to be 3 years old, presented with exophthalmos and fixed abduction of the right eye. Radiographic examination revealed a retrobulbar tumor in the right orbital cavity. The mass was surgically resected but recurred 3 months later and the hedgehog died. There was no gross or microscopic evidence of salivary or lacrimal gland involvement of the tumor at surgery or at necropsy. The histopathologic, immunohistochemical, and ultrastructural findings were those of acinic cell carcinoma, the origin of which was unknown. This is the first known case of acinic cell carcinoma in an African hedgehog.

  4. Pure Small Cell Carcinoma of the Bladder: A Case Report

    PubMed Central

    Trabelsi, Amel; Abdelkrim, Soumaya Ben; Tebra, Samah; Gharbi, Olfa; Jaidane, Lilia; Bouaouina, Noureddine; Abbassi, Dajla Bakir; Mokni, Moncef

    2010-01-01

    Small cell carcinoma of the urinary bladder is an uncommon tumor that has been described in case reports or small series. We report a new case in a 67-year-old male who presented with gross hematuria and irritative symptoms. Cystoscopy revealed an extensive mass of the bladder and computed tomography scan showed an important thickening of the bladder wall. Diagnosis of small cell carcinoma was established after radical cystectomy and microscopic examination. The patient received pelvic hemostatic radiotherapy and platinium-based chemotherapy. Three months after the diagnosis, he developed bone, renal and adrenal metastases. PMID:29147197

  5. Pure Small Cell Carcinoma of the Bladder: A Case Report.

    PubMed

    Trabelsi, Amel; Abdelkrim, Soumaya Ben; Tebra, Samah; Gharbi, Olfa; Jaidane, Lilia; Bouaouina, Noureddine; Abbassi, Dajla Bakir; Mokni, Moncef

    2010-06-01

    Small cell carcinoma of the urinary bladder is an uncommon tumor that has been described in case reports or small series. We report a new case in a 67-year-old male who presented with gross hematuria and irritative symptoms. Cystoscopy revealed an extensive mass of the bladder and computed tomography scan showed an important thickening of the bladder wall. Diagnosis of small cell carcinoma was established after radical cystectomy and microscopic examination. The patient received pelvic hemostatic radiotherapy and platinium-based chemotherapy. Three months after the diagnosis, he developed bone, renal and adrenal metastases.

  6. UOK 268 Cell Line for Hereditary Leiomyomatosis and Renal Cell Carcinoma | NCI Technology Transfer Center | TTC

    Cancer.gov

    The National Cancer Institute’s Urologic Oncology Branch seeks parties to co-develop the UOK 262 immortalized cell line as research tool to study aggressive hereditary leiomyomatosis and renal cell carcinoma (HLRCC)-associated recurring kidney cancer.

  7. Nuclear localization of Merkel cell polyomavirus large T antigen in Merkel cell carcinoma

    SciTech Connect

    Nakamura, Tomoyuki; Sato, Yuko; Watanabe, Daisuke

    2010-03-15

    To clarify whether mutations in the large T gene encoded by Merkel cell polyomavirus affect the expression and function of large T antigen in Merkel cell carcinoma cases, we investigated the expression of large T antigen in vitro and in vivo. Immunohistochemistry using a rabbit polyclonal antibody revealed that large T antigen was expressed in the nuclei of Merkel cell carcinoma cells with Merkel cell polyomavirus infection. Deletion mutant analyses identified an Arg-Lys-Arg-Lys sequence (amino acids 277-280) as a nuclear localization signal in large T antigen. Sequence analyses revealed that there were no mutations in the nuclear localization signal inmore » any of the eleven Merkel cell polyomavirus strains examined. Furthermore, stop codons were not observed in the upstream of the nuclear localization signal in any of the Merkel cell carcinoma cases examined. These data suggest that the nuclear localization signal is highly conserved and functional in Merkel cell carcinoma cases.« less

  8. Mechanism of cisplatin resistance in human urothelial carcinoma cells.

    PubMed

    Yu, Hui-Min; Wang, Tsing-Cheng

    2012-05-01

    An isogenic pair of cisplatin-susceptible (NTUB1) and -resistant (NTUB1/P) human urothelial carcinoma cell lines was used to elucidate the mechanism of cisplatin resistance. The significantly lower intracellular platinum (IP) concentration, which resulted from the decreased cisplatin uptake, was found in NTUB1/P cells. The enhancement of IP concentration did not increase the susceptibility of NTUB1/P cells to cisplatin treatment. The reduction of IP concentration as well was unable to enhance the cisplatin-resistance in susceptible NTUB1 cells. This indicated that reduction of IP concentration was not the account for the development of cisplatin resistance here. Instead, the over expression of anti-apoptotic Bcl-2, anti-oxidative heme oxygenase-1 (HO-1) and cell cycle regulator p16INK4 seemed to be more important for the gaining of cisplatin in these human urothelial carcinoma cell. Copyright © 2012 Elsevier Ltd. All rights reserved.

  9. Oblimersen in Treating Patients With Merkel Cell Carcinoma

    ClinicalTrials.gov

    2013-06-03

    Recurrent Neuroendocrine Carcinoma of the Skin; Stage I Neuroendocrine Carcinoma of the Skin; Stage II Neuroendocrine Carcinoma of the Skin; Stage III Neuroendocrine Carcinoma of the Skin; Stage IV Neuroendocrine Carcinoma of the Skin

  10. Clear cell and endometrioid carcinomas: are their differences attributable to distinct cells of origin?

    PubMed

    Cochrane, Dawn R; Tessier-Cloutier, Basile; Lawrence, Katherine M; Nazeran, Tayyebeh; Karnezis, Anthony N; Salamanca, Clara; Cheng, Angela S; McAlpine, Jessica N; Hoang, Lien N; Gilks, C Blake; Huntsman, David G

    2017-09-01

    Endometrial epithelium is the presumed tissue of origin for both eutopic and endometriosis-derived clear cell and endometrioid carcinomas. We had previously hypothesized that the morphological, biological and clinical differences between these carcinomas are due to histotype-specific mutations. Although some mutations and genomic landscape features are more likely to be found in one of these histotypes, we were not able to identify a single class of mutations that was exclusively present in one histotype and not the other. This lack of genomic differences led us to an alternative hypothesis that these cancers could arise from distinct cells of origin within endometrial tissue, and that it is the cellular context that accounts for their differences. In a proteomic screen, we identified cystathionine γ-lyase (CTH) as a marker for clear cell carcinoma, as it is expressed at high levels in clear cell carcinomas of the ovary and endometrium. In the current study, we analysed normal Müllerian tissues, and found that CTH is expressed in ciliated cells of endometrium (both eutopic endometrium and endometriosis) and fallopian tubes. We then demonstrated that other ciliated cell markers are expressed in clear cell carcinomas, whereas endometrial secretory cell markers are expressed in endometrioid carcinomas. The same differential staining of secretory and ciliated cells was demonstrable in a three-dimensional organoid culture system, in which stem cells were stimulated to differentiate into an admixture of secretory and ciliated cells. These data suggest that endometrioid carcinomas are derived from cells of the secretory cell lineage, whereas clear cell carcinomas are derived from, or have similarities to, cells of the ciliated cell lineage. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  11. Cancer stem cell-like cells from a single cell of oral squamous carcinoma cell lines

    SciTech Connect

    Felthaus, O.; Department of Oral and Maxillofacial Surgery, University of Regensburg; Ettl, T.

    2011-04-01

    Research highlights: {yields} Four oral squamous cancer cell lines (OSCCL) were analyzed for cancer stem cells (CSCs). {yields} Single cell derived colonies of OSCCL express CSC-marker CD133 differentially. {yields} Monoclonal cell lines showed reduced sensitivity for Paclitaxel. {yields} In situ CD133{sup +} cells are slow cycling (Ki67-) indicating a reduced drug sensitivity. {yields} CD133{sup +} and CSC-like cells can be obtained from single colony forming cells of OSCCL. -- Abstract: Resistance of oral squamous cell carcinomas (OSCC) to conventional chemotherapy or radiation therapy might be due to cancer stem cells (CSCs). The development of novel anticancer drugs requires a simplemore » method for the enrichment of CSCs. CSCs can be enriched from OSCC cell lines, for example, after cultivation in serum-free cell culture medium (SFM). In our study, we analyzed four OSCC cell lines for the presence of CSCs. CSC-like cells could not be enriched with SFM. However, cell lines obtained from holoclone colonies showed CSC-like properties such as a reduced rate of cell proliferation and a reduced sensitivity to Paclitaxel in comparison to cells from the parental lineage. Moreover, these cell lines differentially expressed the CSC-marker CD133, which is also upregulated in OSCC tissues. Interestingly, CD133{sup +} cells in OSCC tissues expressed little to no Ki67, the cell proliferation marker that also indicates reduced drug sensitivity. Our study shows a method for the isolation of CSC-like cell lines from OSCC cell lines. These CSC-like cell lines could be new targets for the development of anticancer drugs under in vitro conditions.« less

  12. Cancer stem cell markers in patterning differentiation and in prognosis of oral squamous cell carcinoma.

    PubMed

    Mohanta, Simple; Siddappa, Gangotri; Valiyaveedan, Sindhu Govindan; Dodda Thimmasandra Ramanjanappa, Ravindra; Das, Debashish; Pandian, Ramanan; Khora, Samanta Sekhar; Kuriakose, Moni Abraham; Suresh, Amritha

    2017-06-01

    Differentiation is a major histological parameter determining tumor aggressiveness and prognosis of the patient; cancer stem cells with their slow dividing and undifferentiated nature might be one of the factors determining the same. This study aims to correlate cancer stem cell markers (CD44 and CD147) with tumor differentiation and evaluate their subsequent effect on prognosis. Immunohistochemical analysis in treatment naïve oral cancer patients (n = 53) indicated that the expression of CD147 was associated with poorly differentiated squamous cell carcinoma and moderately differentiated squamous cell carcinoma (p < 0.01). Furthermore, co-expression analysis showed that 45% each of moderately differentiated squamous cell carcinoma and poorly differentiated squamous cell carcinoma patients were CD44 high /CD147 high as compared to only 10% of patients with well-differentiated squamous cell carcinoma. A three-way analysis indicated that differentiation correlated with recurrence and survival (p < 0.05) in only the patients with CD44 high /CD147 high cohort. Subsequently, relevance of these cancer stem cell markers in patterning the differentiation characteristics was evaluated in oral squamous cell carcinoma cell lines originating from different grades of oral cancer. Flowcytometry-based analysis indicated an increase in CD44 + /CD147 + cells in cell lines of poorly differentiated squamous cell carcinoma (94.35 ± 1.14%, p < 0.001) and moderately differentiated squamous cell carcinoma origin (93.49 ± 0.47%, p < 0.001) as compared to cell line of well-differentiated squamous cell carcinoma origin (23.12% ± 0.49%). Expression profiling indicated higher expression of cancer stem cell and epithelial-mesenchymal transition markers in SCC029B (poorly differentiated squamous cell carcinoma originated; p ≤ 0.001), which was further translated into increased spheroid formation, migration, and invasion (p < 0.001) as compared to cell line of well-differentiated squamous

  13. Renal cell carcinoma, unclassified with medullary phenotype: poorly differentiated adenocarcinomas overlapping with renal medullary carcinoma.

    PubMed

    Sirohi, Deepika; Smith, Steven C; Ohe, Chisato; Colombo, Piergiuseppe; Divatia, Mukul; Dragoescu, Ema; Rao, Priya; Hirsch, Michelle S; Chen, Ying-Bei; Mehra, Rohit; Amin, Mahul B

    2017-09-01

    Renal medullary carcinoma (RMC) is a highly aggressive renal cell carcinoma arising in the collecting system and requiring careful correlation with status of sickle cell trait. A panel of international experts has recently proposed provisional diagnostic terminology, renal cell carcinoma, unclassified, with medullary phenotype, based on encountering an extraordinarily rare tumor with RMC morphology and immunophenotype in an individual proven not to have a hemoglobinopathy. Herein, we extend this observation to a cohort of 5 such tumors, morphologically similar to RMC, lacking SMARCB1 expression by immunohistochemistry, but each without evidence of a hemoglobinopathy. The tumors arose in 4 men and 1 woman with a mean age of 44 years, occurring in 3 left and 2 right kidneys. Clinically, aggression was apparent with involvement of perinephric adipose tissue in all 5 cases, nodal metastasis in 4 of 5 cases, and death of disease in 4 of 5 cases within 3-27 months. Histologic sections showed poorly differentiated adenocarcinoma, often with solid and nested growth patterns, as well as infiltrative glandular, tubulopapillary, cribriform, or reticular growth. Rhabdoid and sarcomatoid cytomorphology was seen in a subset. All tumors showed PAX8 nuclear positivity and SMARCB1 loss, with OCT3/4 expression in 4 of 5 cases. In summary, this first series of renal cell carcinoma, unclassified, with medullary phenotype documents tumors with morphologic, immunophenotypic, and prognostic features of RMC occurring in individuals without sickle cell trait. Although greater biologic and molecular understanding is needed, the available evidence points to these cases representing a sporadic counterpart to sickle cell trait-associated RMC. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Complexity of tumor vasculature in clear cell renal cell carcinoma.

    PubMed

    Qian, Chao-Nan; Huang, Dan; Wondergem, Bill; Teh, Bin Tean

    2009-05-15

    Clear cell renal cell carcinoma (CCRCC) is a highly vascularized cancer resistant to conventional chemotherapy and radiotherapy. Antiangiogenic therapy has achieved some effectiveness against this unique malignancy. The complexity of the tumor vasculature in CCRCC has led to differences in correlating tumor microvessel density with patient prognosis. The authors' recent findings demonstrated that there were at least 2 major categories of tumor vessels in CCRCC-namely, undifferentiated and differentiated-correlating with patient prognosis in contrasting ways, with higher undifferentiated vessel density indicating poorer prognosis, and higher differentiated vessel density correlating with better prognosis. Furthermore, the presence of pericytes supporting the differentiated vessels varied in CCRCC. The distributions of pericyte coverage and differentiated vessels in CCRCC were uneven. The tumor margin had a higher pericyte coverage rate for differentiated vessels than did the inner tumor area. The uneven distributions of pericyte coverage and differentiated vessels in CCRCC prompted the authors to revisit the mechanism of tumor central necrosis, which was also known to be a prognostic indicator for CCRCC. The discrepancy of prognostic correlation between protein and messenger RNA levels of vascular endothelial growth factor in CCRCC was discussed. The complexity of the tumor vasculature in CCRCC also led the authors to begin to re-evaluate the therapeutic effects of antiangiogenic agents for each type of tumor vessel, which will in turn significantly broaden understanding of tumor angiogenesis and improve therapeutic effect. (c) 2009 American Cancer Society.

  15. COMPREHENSIVE MOLECULAR CHARACTERIZATION OF CLEAR CELL RENAL CELL CARCINOMA

    PubMed Central

    2013-01-01

    Genetic changes underlying clear cell renal cell carcinoma (ccRCC) include alterations in genes controlling cellular oxygen sensing (e.g. VHL) and the maintenance of chromatin states (e.g. PBRM1). We surveyed more than 400 tumors using different genomic platforms and identified 19 significantly mutated genes. The PI3K/Akt pathway was recurrently mutated, suggesting this pathway as a potential therapeutic target. Widespread DNA hypomethylation was associated with mutation of the H3K36 methyltransferase SETD2, and integrative analysis suggested that mutations involving the SWI/SNF chromatin remodeling complex (PBRM1, ARID1A, SMARCA4) could have far-reaching effects on other pathways. Aggressive cancers demonstrated evidence of a metabolic shift, involving down-regulation of genes involved in the TCA cycle, decreased AMPK and PTEN protein levels, up-regulation of the pentose phosphate pathway and the glutamine transporter genes, increased acetyl-CoA carboxylase protein, and altered promoter methylation of miR-21 and GRB10. Remodeling cellular metabolism thus constitutes a recurrent pattern in ccRCC that correlates with tumor stage and severity and offers new views on the opportunities for disease treatment. PMID:23792563

  16. [Basal cell carcinoma of the nose].

    PubMed

    Bonvallot, T; Raulo, Y; Zeller, J; Faivre, J M; Horn, G; Baruch, J

    1993-01-01

    The purpose of this study of 81 patients with basal cell carcinoma (BCC) of the nose was to present the oncological and cosmetic results of surgical treatment and compare these results with those of other possible treatments. We report a series of 81 cases of histologically proven BCC of the nose located chiefly on the alae nasi and on the lower end of this organ; 42 p. 100 of the tumors had previously been treated and had recurred. The patients' mean age was 63 years, and the shortest follow-up was 3 years. Excision of the tumor under simple or reinforced local anaesthesia was complete in 88 p. 100 of the cases, incomplete or borderline in 12 p. 100 and systematically repeated. Extemporaneous histological examination was performed in 18 p. 100 of the cases. The operative lesion was repaired with a graft or a flap. There was no postsurgical treatment. The recurrence rate was 4 p. 100 with a minimum follow-up of 3 years. The cosmetic result was good in 78 p. 100 of the patients. Numerous treatments have been used against BCC of the nose, the results, advantages and disadvantages of each of these treatments are given below: 1. Cryosurgery. The problem with this method is that it is relatively difficult to perform and requires reliable operators. The cure rate is similar to that of other treatments. 2. Chemotherapy is not frequently used. 3. Electrocoagulation. Contrary to the conventional excision, this method precludes all histological controls, and the common idea of good oncological results is now being revised. 4. Radiotherapy. The recurrence rate varies from 7 to 11.8 p. 100 with fair cosmetic results. It requires numerous sessions, cannot be repeated in case of recurrence and complicates the surgical treatment. In addition, there is a long-term risk of radiodystrophy. 5. Curietherapy by local implantation of 192Iridium has a recurrence rate of 2.5 to 7 p. 100. This treatment requires hospitalization and is costly. It is indicated in cases of complex surgery

  17. SQUAMOUS CELL CARCINOMA IN THE GULF MENHADEN, 'BREVOORTIA PATRONUS' GOODE

    EPA Science Inventory

    The communication reports a case (RTLA 3618) of squamous cell carcinoma from the gulf menhaden, Brevoortia patronus Goode, the first tumor reported from the species. The affected fish was collected in a gill net on 15 January 1986 in the northern Gulf of Mexico near Round Island,...

  18. Genetic drivers of papillary renal cell carcinoma - TCGA

    Cancer.gov

    A comprehensive genomic analysis of 161 tumors from people with papillary renal cell carcinoma (PRCC) – the second most common form of kidney cancer –provided insights into the molecular basis of this cancer and may inform its classification and treatment.

  19. Genetics Home Reference: head and neck squamous cell carcinoma

    MedlinePlus

    ... Lyons B, Fox SB, Rischin D, Dobrovic A, Solomon B. Differential mechanisms of CDKN2A (p16) alteration in oral tongue squamous cell carcinomas and correlation with patient outcome. Int J Cancer. 2014 Aug 15;135(4):887-95. doi: 10.1002/ijc.28727. Epub ...

  20. Pancreatic panniculitis as a presentation symptom of acinar cell carcinoma.

    PubMed

    de Frutos Rosa, Diego; Espinosa Taranilla, Laura; González de Canales de Simón, Pilar; Vélez Velázquez, María Dolores; Guirado Koch, Cristina

    2018-05-01

    Pancreatic panniculitis is a rare skin manifestation associated with pancreatic conditions. This condition has similar characteristics to those of other panniculitis types and its course parallels the triggering condition and may occasionally precede it. We report the case of a female patient with asymptomatic pancreatic panniculitis; the etiologic study identified a pancreatic acinar cell carcinoma with liver metastases.

  1. Re-irradiation for head and neck squamous cell carcinoma.

    PubMed

    Benson, Rony; Giridhar, Prashant; Venkatesulu, Bhanu Prasad; Mallick, Supriya; Raza, Mohd Waseem; Rath, Goura Kishor

    2017-03-01

    Local recurrences after curative treatment have a potential for cure with salvage surgery or with re-irradiation. We reviewed the PubMed for articles published in English with key words squamous cell carcinoma, recurrent, re-irradiation, prognostic factors to find relevant articles describing prognostic factors, re-irradiation, and outcome for recurrent head and neck squamous cell carcinoma. Various factors including age, performance status, time for recurrence, previous radiation dose volume and site of recurrence, previous use of chemotherapy are all prognostic factors in recurrent head and neck squamous cell carcinoma. Surgery is feasible in very select subgroup of patients and must be done when feasible. Re-irradiation with the aid of modern sophisticated technology is safe and confers durable and clinically meaningful survival benefit. Re-irradiation in head and neck recurrent squamous cell carcinoma may provide an expected median survival of 10-12months. Chemotherapy may be added along with radiation in the recurrent setting. Treatment approaches may have to be personalized. Re surgery must be done in all patients in whom it is feasible. In patients in whom surgery is not feasible, re-irradiation must be evaluated as a therapeutic option especially in patients with limited volume recurrence. Copyright © 2016 National Cancer Institute, Cairo University. Production and hosting by Elsevier B.V. All rights reserved.

  2. Human papillomavirus type 16 DNA in periungual squamous cell carcinomas

    SciTech Connect

    Moy, R.L.; Eliezri, Y.D.; Bennett, R.G.

    1989-05-12

    Ten squamous cell carcinomas (in situ or invasive) of the fingernail region were analyzed for the presence of DNA sequences homologous to human papilloma-virus (HPV) by dot blot hybridization. In most patients, the lesions were verrucae of long-term duration that were refractory to conventional treatment methods. Eight of the lesions contained HPV DNA sequences, and in six of these the sequences were related to HPV 16 as deduced from low-stringency nucleic acid hybridization followed by low- and high-stringency washes. Furthermore, the restriction endonuclease digestion pattern of DNA isolated from four of these lesions was diagnostic of episomal HPV 16. Themore » high-frequency association of HPV 16 with periungual squamous cell carcinoma is similar to that reported for HPV 16 with squamous cell carcinomas on mucous membranes at other sites, notably the genital tract. The findings suggest that HPV 16 may play an important role in the development of squamous cell carcinomas of the finger, most notably those lesions that are chronic and located in the periungual area.« less

  3. Basal cell carcinoma of the vulva: a case series.

    PubMed

    Mulvany, Nicholas J; Rayoo, Mukta; Allen, David G

    2012-10-01

    To review the diagnostic features and characteristics of an uncommon tumour, basal cell carcinoma (BCC) of the vulva. The clinical and pathological details of six vulvar BCCs were reviewed. Four of the BCCs arose in isolation, one was combined with vulvar Paget's disease and another was intimately associated with a poorly differentiated squamous cell carcinoma. The average age of the six patients was 76 years (75 years for 'isolated' BCC; 78 years for BCC 'mixed' with other lesions). The duration of symptoms averaged 13 months in 'isolated' BCC but 24 months in 'mixed' BCC. Vulvar pruritus was the most common presenting complaint in the four cases of 'isolated' BCC. The initial biopsies included shave (× 2) or punch biopsies (× 4). Definitive surgery included excisional biopsy (× 2) or a wide local excision (× 3). In the five assessable tumours, the maximum tumour diameter averaged 19.8 mm (range 11-36 mm). In the sixth patient the BCC was contiguous with a 70 mm, unresectable, poorly differentiated squamous cell carcinoma which was treated by radiotherapy alone. : Although the histological diagnosis of vulvar BCC was straightforward in some of our cases, others presented difficulties due to non-representative initial biopsies, insufficient clinical information or contiguity with lesions of greater clinical significance such as Paget's disease or squamous cell carcinoma.

  4. Esophageal squamous cell carcinoma with dural and bone marrow metastases.

    PubMed

    Chen, Yen-Hao; Huang, Cheng-Hua

    2014-09-21

    Patients with esophageal squamous cell carcinoma generally present at an advanced stage at the time of diagnosis. The most common sites of visceral metastasis are the lung, liver and bone, but brain and bone marrow involvement is exceedingly rare. Herein, we report a 62-year-old man with a 4-wk history of progressive low back pain with radiation to bilateral lower legs, dysphagia and body weight loss. Esophageal squamous cell carcinoma with regional lymph node, liver and bone metastases was diagnosed. He underwent concurrent chemoradiotherapy and got a partial response. Four months later, he complained of headache, diplopia and severe hearing impairment in the left ear. There was no evidence for bacterial, fungal, tuberculous infection or neoplastic infiltration. Magnetic resonance imaging of the brain demonstrated thickening and enhancement of bilateral pachymeninges and multiple enhancing masses in bilateral skull. Dural metastasis was diagnosed and he received whole brain irradiation. In addition, laboratory examination revealed severe thrombocytopenia and leucopenia, and bone marrow study confirmed the diagnosis of metastatic squamous cell carcinoma. This is the first described case of esophageal squamous cell carcinoma with dural and bone marrow metastases. We also discuss the pathogenesis of unusual metastatic diseases and differential diagnosis of pachymeningeal thickening.

  5. Basal cell carcinoma of the nipple. Report of two cases.

    PubMed

    Cain, R J; Sau, P; Benson, P M

    1990-02-01

    Two cases of basal cell carcinoma of the nipple are presented, bringing the total number of reported cases to 15. The majority, including our two patients, are elderly men. This finding suggests a causal role of exposure to ultraviolet radiation. In our cases excision was curative.

  6. 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.

  7. 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

  8. Basal Cell Carcinoma in Cases with or without Xeroderma Pigmentosum.

    PubMed

    Ghartimagar, Dilasma; Ghosh, Arnab; Shrestha, Sushil Ram; Shrestha, Sachet; Thapa, Sushma; Narasimhan, Raghavan; Talwar, O P

    2017-01-01

    Basal cell carcinoma is the most common form of cancer in humans and comprises the vast majority of skin cancers. It predominantly affects fair-skinned individuals, and its incidence is rapidly increasing. The objective of the study is to identify the epidemiology, its topography and different histological subtypes of basal cell carcinoma in patients with or without Xeroderma Pigmentosum. A cross-sectional descriptive study was conducted at Manipal Teaching Hospital, Pokhara from Jan 2009 to Dec 2016. Ethical approval was taken from MEMG/IRC/GA. The study included patients with a confirmed diagnosis of basal cell carcinoma irrespective of their age and sex. This study showed 77 individuals with 91 biopsies of BCC including 5 cases of Xeroderma Pigmentosum. The predominant histological subtype was nodular with 41 (53.94%) cases, followed by the 14 (18.42%) cases of pigmented and 10 (13.15%) cases baso-squamous subtype. The most frequent sites of involvement were the head and neck, with predominance in the nasal and orbital region. The mean age was 57.68 years but the basal cell carcinoma in cases of Xeroderma Pigmentosum was seen more in younger age groups. There were 43 (55.84 %) male patients and 34 (44.16 %) female patients with a male to female ratio of 1.26:1. Nodular and pigmented varieties were the most frequent subtypes with nose being the commonest site of involvement. Basal cell carcinomas in cases of Xeroderma Pigmentosum were noted in younger age group with multiple lesions.

  9. GLUT-1 immunoexpression in oral epithelial dysplasia, oral squamous cell carcinoma, and verrucous carcinoma.

    PubMed

    Angadi, Vidya C; Angadi, Punnya V

    2015-06-01

    Glucose transporters, such as GLUT-1, mediate the important mechanisms involved in cellular glucose influx, allowing cells to proliferate and survive. The significance of GLUT-1 expression in oral epithelial dysplasia (OED) and oral squamous cell carcinoma (OSCC) has been less explored, and no study has investigated it in relation to verrucous carcinoma (VC). We evaluated 30 cases each of OED, OSCC, and VC, graded further on the basis of their differentiation, immunohistochemically for GLUT-1 expression, along with 10 specimens of normal oral mucosa (NOM) as controls. In OSCC, GLUT-1 expression increased with the degree of dysplasia and increasing grade (P < 0.001). The expression in VC was predominantly membranous and intense, resembling well differentiated OSCC. This increase of GLUT-1 expression in OSCC along with the degree of dysplasia and the histologic grade reflects the expanding glycolytic response to hypoxia. This is the first study to have revealed prominent GLUT-1 expression in VC, highlighting its inherent metabolic capacity.

  10. Poorly Differentiated Squamous Cell Carcinoma Arising in Tattooed Skin

    PubMed Central

    Sarma, Deba P.; Dentlinger, Renee B.; Forystek, Amanda M.; Stevens, Todd; Huerter, Christopher

    2010-01-01

    Introduction. Tattoos have increasingly become accepted by mainstream Western society. As a result, the incidence of tattoo-associated dermatoses is on the rise. The presence of a poorly differentiated squamous cell carcinoma in an old tattooed skin is of interest as it has not been previously documented. Case Presentation. A 79-year-old white homeless man of European descent presented to the dermatology clinic with a painless raised nodule on his left forearm arising in a tattooed area. A biopsy of the lesion revealed a poorly differentiated squamous cell carcinoma infiltrating into a tattoo. The lesion was completely excised and the patient remains disease-free one year later. Conclusion. All previous reports of squamous cell carcinomas arising in tattoos have been well-differentiated low-grade type or keratoacanthoma-type and are considered to be coincidental rather than related to any carcinogenic effect of the tattoo pigments. Tattoo-associated poorly differentiated invasive carcinoma appears to be extremely rare. PMID:21274289

  11. p16 expression is not associated with human papillomavirus in urinary bladder squamous cell carcinoma.

    PubMed

    Alexander, Riley E; Hu, Yingchuan; Kum, Jennifer B; Montironi, Rodolfo; Lopez-Beltran, Antonio; Maclennan, Gregory T; Idrees, Muhammad T; Emerson, Robert E; Ulbright, Thomas M; Grignon, David G; Eble, John N; Cheng, Liang

    2012-11-01

    Squamous cell carcinoma of the urinary bladder is unusual and of unknown etiology. There is a well-established association between human papillomavirus (HPV) infection and the development of cervical and head/neck squamous cell carcinomas. However, the role of HPV in the pathogenesis of squamous cell carcinoma of the urinary bladder is uncertain. The purposes of this study were to investigate the possible role of HPV in the development of squamous cell carcinoma of the urinary bladder and to determine if p16 expression could serve as a surrogate marker for HPV in this malignancy. In all, 42 cases of squamous cell carcinoma of the urinary bladder and 27 cases of urothelial carcinoma with squamous differentiation were investigated. HPV infection was analyzed by both in situ hybridization at the DNA level and immunohistochemistry at the protein level. p16 protein expression was analyzed by immunohistochemistry. HPV DNA and protein were not detected in 42 cases of squamous cell carcinoma (0%, 0/42) or 27 cases of urothelial carcinoma with squamous differentiation (0%, 0/15). p16 expression was detected in 13 cases (31%, 13/42) of squamous cell carcinoma and 9 cases (33%, 9/27) of urothelial carcinoma with squamous differentiation. There was no correlation between p16 expression and the presence of HPV infection in squamous cell carcinoma of the bladder or urothelial carcinoma with squamous differentiation. Our data suggest that HPV does not play a role in the development of squamous cell carcinoma of the urinary bladder or urothelial carcinoma with squamous differentiation. p16 expression should not be used as a surrogate marker for evidence of HVP infection in either squamous cell carcinoma of the urinary bladder or urothelial carcinoma with squamous differentiation as neither HVP DNA nor protein is detectable in these neoplasms.

  12. Microarray profile of human kidney from diabetes, renal cell carcinoma and renal cell carcinoma with diabetes

    PubMed Central

    Kosti, Adam; Harry Chen, Hung-I; Mohan, Sumathy; Liang, Sitai; Chen, Yidong; Habib, Samy L.

    2015-01-01

    Recent study from our laboratory showed that patients with diabetes are at a higher risk of developing kidney cancer. In the current study, we have screened whole human DNA genome from healthy control, patients with diabetes or renal cell carcinoma (RCC) or RCC+diabetes. We found that 883 genes gain/163 genes loss of copy number in RCC+diabetes group, 669 genes gain/307 genes loss in RCC group and 458 genes gain/38 genes loss of copy number in diabetes group, after removing gain/loss genes obtained from healthy control group. Data analyzed for functional annotation enrichment pathways showed that control group had the highest number (280) of enriched pathways, 191 in diabetes+RCC group, 148 in RCC group, and 81 in diabetes group. The overlap GO pathways between RCC+diabetes and RCC groups showed that nine were enriched, between RCC+diabetes and diabetes groups was four and between diabetes and RCC groups was eight GO pathways. Overall, we observed majority of DNA alterations in patients from RCC+diabetes group. Interestingly, insulin receptor (INSR) is highly expressed and had gains in copy number in RCC+diabetes and diabetes groups. The changes in INSR copy number may use as a biomarker for predicting RCC development in diabetic patients. PMID:25821562

  13. Differential senescence capacities in meibomian gland carcinoma and basal cell carcinoma.

    PubMed

    Zhang, Leilei; Huang, Xiaolin; Zhu, Xiaowei; Ge, Shengfang; Gilson, Eric; Jia, Renbing; Ye, Jing; Fan, Xianqun

    2016-03-15

    Meibomian gland carcinoma (MGC) and basal cell carcinoma (BCC) are common eyelid carcinomas that exhibit highly dissimilar degrees of proliferation and prognoses. We address here the question of the differential mechanisms between these two eyelid cancers that explain their different outcome. A total of 102 confirmed MGC and 175 diagnosed BCC cases were analyzed. Twenty confirmed MGC and twenty diagnosed BCC cases were collected to determine the telomere length, the presence of senescent cells, and the expression levels of the telomere capping shelterin complex, P53, and the E3 ubiquitin ligase Siah1. Decreased protein levels of the shelterin subunits, shortened telomere length, over-expressed Ki-67, and Bcl2 as well as mutations in P53 were detected both in MGC and BCC. It suggests that the decreased protein levels of the shelterin complex and the shortened telomere length contribute to the tumorigenesis of MGC and BCC. However, several parameters distinguish MGC from BCC samples: (i) the mRNA level of the shelterin subunits decreased in MGC but it increased in BCC; (ii) P53 was more highly mutated in MGC; (iii) Siah1 mRNA was over-expressed in BCC; (iv) BCC samples contain a higher level of senescent cells; (v) Ki-67 and Bcl2 expression were lower in BCC. These results support a model where a preserved P53 checkpoint in BCC leads to cellular senescence and reduced tumor proliferation as compared to MGC. © 2015 UICC.

  14. Cell culture of the mucinous variant of human colorectal carcinoma.

    PubMed

    Tibbetts, L M; Chu, M Y; Vezeridis, M P; Miller, P G; Tibbetts, L L; Poisson, M H; Camara, P D; Calabresi, P

    1988-07-01

    Two cell lines, RW-2982 and RW-7213, have been established for the first time from the mucinous variant of human colorectal carcinoma, which is a distinctive and important subtype that has a worse prognosis than the more common nonmucogenic large bowel carcinoma. Methods of establishment and observations made during 7 and 3 years, respectively, of continuous culture are described. These cell lines required 4-9 months of adaptation to tissue culture conditions before noticeable growth occurred. Both cell lines have the following unique properties: (a) growth in vitro as delicate branching three-dimensional tumor particles within a wide gel of insoluble, often translucent mucus (proteoglycan); (b) production of large quantities of carcinoembryonic antigen; (c) ability to survive or adapt to growth in media free of serum, hormones, growth factors, and all protein; and (d) tumorigenicity in multiple sites in nude mice, including liver, with especially rapid growth in the peritoneal cavity as gelatinous material that is nonadherent and noninvasive and thus resembles pseudomyxoma peritonei. Unlike other reported colorectal cell lines, these mucus-coated particulate cell lines will not readily grow as monolayers and grow much more slowly with a doubling time of 2 weeks or more. A serially transplantable tumor from the RW-7213 surgical specimen has also been maintained in nude mice since August 8, 1984. This tumor retains properties of the original specimen. Observations made on the tumor biology of mucogenic colorectal carcinoma using these cell lines are discussed.

  15. In vitro perforation of human epithelial carcinoma cell with antibody-conjugated biodegradable microspheres illuminated by a single 80 femtosecond near-infrared laser pulse

    PubMed Central

    Terakawa, Mitsuhiro; Tsunoi, Yasuyuki; Mitsuhashi, Tatsuki

    2012-01-01

    Pulsed laser interaction with small metallic and dielectric particles has been receiving attention as a method of drug delivery to many cells. However, most of the particles are attended by many risks, which are mainly dependent upon particle size. Unlike other widely used particles, biodegradable particles have advantages of being broken down and eliminated by innate metabolic processes. In this paper, the perforation of cell membrane by a focused spot with transparent biodegradable microspheres excited by a single 800 nm, 80 fs laser pulse is demonstrated. A polylactic acid (PLA) sphere, a biodegradable polymer, was used. Fluorescein isothiocyanate (FITC)-dextran and short interfering RNA were delivered into many human epithelial carcinoma cells (A431 cells) by applying a single 80 fs laser pulse in the presence of antibody-conjugated PLA microspheres. The focused intensity was also simulated by the three-dimensional finite-difference time-domain method. Perforation by biodegradable spheres compared with other particles has the potential to be a much safer phototherapy and drug delivery method for patients. The present method can open a new avenue, which is considered an efficient adherent for the selective perforation of cells which express the specific antigen on the cell membrane. PMID:22679375

  16. Squamous cell carcinoma presenting as an endodontic-periodontic lesion.

    PubMed

    Levi, Paul A; Kim, David M; Harsfield, Scott L; Jacobson, Erica R

    2005-10-01

    Regardless of advances in diagnosis and treatment during the past 40 years, the overall 5-year survival rates for oral and oropharyngeal squamous cancers have only slightly improved and remain around 50%. Thus, the early diagnosis and treatment of carcinoma by health care providers are essential in achieving a good prognosis. We report a case of invasive squamous cell carcinoma that presented as a benign endodontic-periodontic lesion with a 7-mm periodontal pocket on tooth #15 in a 40-year-old, non-smoking woman. The subsequent management of the case is also discussed. The study was conducted in accordance with the Helsinki Declaration of 1975, as revised in 2000. Our patient was seen for a comprehensive periodontal examination including a periodontal charting, occlusal analysis, study casts, electronic pulp test for tooth #15, and complete mouth periapical radiographs. As there was a periapical radiolucency, an endodontic consultation was obtained. A periodontal flap surgical procedure was performed on teeth #13 to #15, and as there was bone erosion into the maxillary sinus, a biopsy of the soft tissue was submitted to the local hospital for histological analysis. The biopsied lesion was diagnosed as invasive, moderately differentiated squamous cell carcinoma with focal spindle and clear cell differentiation (grade II to III of IV). Bone invasion was also identified. The treatment of the carcinoma involved a hemimaxillectomy with the removal of the maxillary left posterior teeth. The patient remained free of tumor for 5 years after the initial presentation. Patient education and periodic oral cancer examinations by dental professionals are necessary to reduce diagnostic delay and improve prognosis. This case report emphasizes the important role of dental professionals, especially periodontists and endodontists, of being aware that squamous cell carcinoma may manifest itself clinically and/or radiographically as a common periodontal or endodontic lesion.

  17. Detection and Characterization of Carcinoma Cells in the Blood

    NASA Astrophysics Data System (ADS)

    Racila, Emilian; Euhus, David; Weiss, Arthur J.; Rao, Chandra; McConnell, John; Terstappen, Leon W. M. M.; Uhr, Jonathan W.

    1998-04-01

    A highly sensitive assay combining immunomagnetic enrichment with multiparameter flow cytometric and immunocytochemical analysis has been developed to detect, enumerate, and characterize carcinoma cells in the blood. The assay can detect one epithelial cell or less in 1 ml of blood. Peripheral blood (10-20 ml) from 30 patients with carcinoma of the breast, from 3 patients with prostate cancer, and from 13 controls was examined by flow cytometry for the presence of circulating epithelial cells defined as nucleic acid+, CD45-, and cytokeratin+. Highly significant differences in the number of circulating epithelial cells were found between normal controls and patients with cancer including 17 with organ-confined disease. To determine whether the circulating epithelial cells in the cancer patients were neoplastic cells, cytospin preparations were made after immunomagnetic enrichment and were analyzed. Epithelial cells from patients with breast cancer generally stained with mAbs against cytokeratin and 3 of 5 for mucin-1. In contrast, no cells that stained for these antigens were observed in the blood from normal controls. The morphology of the stained cells was consistent with that of neoplastic cells. Of 8 patients with breast cancer followed for 1-10 months, there was a good correlation between changes in the level of tumor cells in the blood with both treatment with chemotherapy and clinical status. The present assay may be helpful in early detection, in monitoring disease, and in prognostication.

  18. Renal cell carcinoma containing abundant non-calcified fat.

    PubMed

    Wasser, Elliot J; Shyn, Paul B; Riveros-Angel, Marcela; Sadow, Cheryl A; Steele, Graeme S; Silverman, Stuart G

    2013-06-01

    Renal masses found to contain macroscopic fatty elements on CT or MRI imaging can generally be classified as benign angiomyolipomas. Rarely, renal cell carcinomas may also contain evidence of macroscopic fat. When true adipocytic elements are present, this is generally due to a process of osseous metaplasia in which both fat cells and calcification are co-localized within the mass. We present a patient with a large papillary renal cell carcinoma containing abundant fat with sparse, punctate calcification remote from the fatty elements on imaging. This report highlights the need for radiologists to maintain caution when diagnosing renal angiomyolipomas on the basis of macroscopic fat and reviews the current literature on fat-containing renal masses.

  19. Granulomatous inflammation of pulmonary squamous cell carcinoma: a rare phenomenon.

    PubMed

    Tajima, Shogo; Koda, Kenji

    2015-01-01

    Some neoplasms are associated with granulomatous inflammation. Granuloma formation in tumor tissue is caused by the cytokines derived from either the main tumor or other cells surrounding the tumor. In other instances, granulomatous inflammation is observed in the lymph nodes draining a tumor. This has been recognized as a sarcoid-like reaction. Herein, we report of a 75-year-old man with pulmonary squamous cell carcinoma (SCC), where granulomatous inflammation was observed extensively at the primary site. The carcinoma seemed to partly regress. In the regressing area, tumor cell debris was surrounded by granuloma. In contrast, no granuloma was identified in the dissected regional lymph nodes. To the best of our knowledge, such a case of SCC had not been described thus far. More case studies are required to determine whether tumor-related granuloma is the main cause of regression or whether it is just a secondary phenomenon caused by the attack and destruction of the tumor by lymphocytes.

  20. DPPIV promotes endometrial carcinoma cell proliferation, invasion and tumorigenesis

    PubMed Central

    Yang, Xiaoqing; Zhang, Xinhua; Wu, Rongrong; Huang, Qicheng; Jiang, Yao; Qin, Jianbing; Yao, Feng; Jin, Guohua; Zhang, Yuquan

    2017-01-01

    Dipeptidyl peptidase IV (DPPIV), also known as CD26, is a 110-kDa cell surface glycoprotein expressed in various tissues. DPPIV reportedly plays a direct role in the progression of several human malignancies. DPPIV specific inhibitors are employed as antidiabetics and could potentially be repurposed to enhance anti-tumor immunotherapies. In the present study, we investigated the correlation between DPPIV expression and tumor progression in endometrial carcinoma (EC). DPPIV overexpression altered cell morphology and stimulated cell proliferation, invasion and tumorigenesis in vitro and in vivo. These effects were abrogated by DPPIV knockdown or pharmacological inhibition using sitagliptin. DPPIV overexpression increased hypoxia-inducible factor 1a (HIF-1a) and vascular endothelial growth factor A (VEGFA) expression to promote HIF-1a-VEGFA signaling. Our results indicated that DPPIV accelerated endometrial carcinoma progression and that sitagliptin may be an effective anti-EC therapeutic. PMID:28060721

  1. Squamous cell carcinoma of the anal sac in five dogs.

    PubMed

    Esplin, D G; Wilson, S R; Hullinger, G A

    2003-05-01

    Tumors of the perianal area of dogs are common and include multiple tumor types. Whereas perianal adenomas occur often, adenocarcinomas of the apocrine glands of the anal sac occur less frequently. A review of the literature revealed no reports of squamous cell carcinomas arising from the epithelial lining of the anal sac. Squamous cell carcinomas originating from the lining of the anal sac were diagnosed in five dogs. Microscopically, the tumors consisted of variably sized invasive nests and cords of epithelial cells displaying squamous differentiation. Four of the five dogs were euthanatized because of problems associated with local infiltration by the tumors. In the fifth dog, there was no evidence of tumor 7 months after surgical removal, but further follow up was not available.

  2. DPPIV promotes endometrial carcinoma cell proliferation, invasion and tumorigenesis.

    PubMed

    Yang, Xiaoqing; Zhang, Xinhua; Wu, Rongrong; Huang, Qicheng; Jiang, Yao; Qin, Jianbing; Yao, Feng; Jin, Guohua; Zhang, Yuquan

    2017-01-31

    Dipeptidyl peptidase IV (DPPIV), also known as CD26, is a 110-kDa cell surface glycoprotein expressed in various tissues. DPPIV reportedly plays a direct role in the progression of several human malignancies. DPPIV specific inhibitors are employed as antidiabetics and could potentially be repurposed to enhance anti-tumor immunotherapies. In the present study, we investigated the correlation between DPPIV expression and tumor progression in endometrial carcinoma (EC). DPPIV overexpression altered cell morphology and stimulated cell proliferation, invasion and tumorigenesis in vitro and in vivo. These effects were abrogated by DPPIV knockdown or pharmacological inhibition using sitagliptin. DPPIV overexpression increased hypoxia-inducible factor 1a (HIF-1a) and vascular endothelial growth factor A (VEGFA) expression to promote HIF-1a-VEGFA signaling. Our results indicated that DPPIV accelerated endometrial carcinoma progression and that sitagliptin may be an effective anti-EC therapeutic.

  3. Primary cutaneous neuroendocrine carcinoma, Merkel cell carcinoma. Case series 1991-2012.

    PubMed

    Campillo, Ramón; Gil-Carcedo, Elisa; Alonso, David; Vallejo, Luis A; Oñate, Juan M; Gil-Carcedo, Luis M

    2013-01-01

    Merkel cell carcinoma was first described by Toker in 1972. It is an uncommon, primary neuroendocrine skin carcinoma which appears in the dermoepidermic area, grows fast, is very aggressive and has a poor prognosis. The aim of this work is to highlight the importance of this tumour, which develops mainly in the skin of the head and neck area, and whose prevalence has increased in recent years. We gathered data on 16 patients suffering cutaneous neuroendocrine carcinoma treated at our hospital between September 12, 1991 and July 13, 2012. We indicated the age and gender of patients. We described the area where the tumour was located, indicating the size in millimetres, according to the major axis of the lesion. Most of the patients studied were over 70 years old, except for one who was 55. The highest frequency of cases appeared among patients aged over 80 years. In the cases studied, when the tumour appeared in the head and neck region (10/16), its location could be nasal-lateronasal, cheek-malar, upper eyelid, frontal or mandibular. The major axis of the lesion ranged between 7 and 35 mm. Unlike with epidermoid or basocellular carcinomas, recurrence and ganglionar metastases were common. Immunohistochemical (CK20) tests are essential for a correct diagnosis. Treatment is usually surgical and occasionally followed by radiotherapy and chemotherapy. This carcinoma is not a very common skin tumour. It appears in old age, in the head and neck region in 50% of cases and often leads to exitus. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  4. Altered gene expression in conjunctival squamous cell carcinoma.

    PubMed

    Mahale, Alka; Alkatan, Hind; Alwadani, Saeed; Othman, Maha; Suarez, Maria J; Price, Antoinette; Al-Hussain, Hailah; Jastaneiah, Sabah; Yu, Wayne; Maktabi, Azza; Deepak, Edward P; Eberhart, Charles G; Asnaghi, Laura

    2016-05-01

    Conjunctival squamous cell carcinoma is a malignancy of the ocular surface. The molecular drivers responsible for the development and progression of this disease are not well understood. We therefore compared the transcriptional profiles of eight snap-frozen conjunctival squamous cell carcinomas and one in situ lesion with normal conjunctival specimens in order to identify diagnostic markers or therapeutic targets. RNA was analyzed using oligonucleotide microarrays, and a wide range of transcripts with altered expression identified, including many dysregulated in carcinomas arising at other sites. Among the upregulated genes, we observed more than 30-fold induction of the matrix metalloproteinases, MMP-9 and MMP-11, as well as a prominent increase in the mRNA level of a calcium-binding protein important for the intracellular calcium signaling, S100A2, which was induced over 20-fold in the tumor cohort. Clusterin was the most downregulated gene, with an approximately 180-fold reduction in the mRNA expression. These alterations were all confirmed by qPCR in the samples used for initial microarray analysis. In addition, immunohistochemical analysis confirmed the overexpression of MMP-11 and S100A2, as well as reductions in clusterin, in several independent in situ carcinomas of conjunctiva. These data identify a number of alterations, including upregulation of MMP-9, MMP-11, and S100A2, as well as downregulation of clusterin, associated with epithelial tumorigenesis in the ocular surface.

  5. Hürthle cell carcinoma of the thyroid presenting as thyrotoxicosis.

    PubMed

    Karanchi, Harsha; Hamilton, Dale J; Robbins, Richard J

    2012-01-01

    To report a case of hyperthyroidism associated with Hürthle cell carcinoma and to review the literature regarding this relationship. We describe the clinical, biochemical, radiologic, and pathologic data of a patient with Hürthle cell carcinoma associated with thyrotoxicosis and reversible heart failure. We discuss the mechanistic aspects and review previously reported cases of functional Hürthle cell carcinomas. A 43-year-old woman presented with thyrotoxicosis and nonischemic cardiomyopathy. She had a "hot" nodule in the left lobe of the thyroid on sodium pertechnetate scan. She underwent a left hemithyroidectomy and isthmusectomy. Pathologic findings revealed a minimally invasive Hürthle cell carcinoma. On follow-up, the dilated cardiomyopathy had resolved. The association of thyroid carcinoma with thyrotoxicosis is rare. Some Hürthle cell carcinomas can be functional and lead to thyrotoxicosis. To our knowledge, we present the first case of reversible dilated cardiomyopathy due to thyrotoxicosis originating from Hürthle cell carcinoma.

  6. Culture and Characterization of Circulating Endothelial Progenitor Cells in Patients with Renal Cell Carcinoma.

    PubMed

    Gu, Wenyu; Sun, Wei; Guo, Changcheng; Yan, Yang; Liu, Min; Yao, Xudong; Yang, Bin; Zheng, Junhua

    2015-07-01

    Although emerging evidence demonstrates increased circulating endothelial progenitor cells in patients with solid tumors, to our knowledge it is still unknown whether such cells can be cultured from patients with highly angiogenic renal cell carcinoma. We cultured and characterized circulating endothelial progenitor cells from patients with renal cell carcinoma. The circulating endothelial progenitor cell level (percent of CD45(-)CD34(+) VEGF-R2(+) cells in total peripheral blood mononuclear cells) was quantified in 47 patients with renal cell carcinoma and 40 healthy controls. Peripheral blood mononuclear cells were then isolated from 33 patients with renal cell carcinoma and 30 healthy controls to culture and characterize circulating endothelial progenitor cells. The circulating endothelial progenitor cell level was significantly higher in patients with renal cell carcinoma than in healthy controls (0.276% vs 0.086%, p <0.001). A colony of circulating endothelial progenitor cells first emerged significantly earlier in patient than in control preparations (6.72 vs 14.67 days, p <0.001). The culture success rate (87.8% vs 40.0% of participants) and the number of colonies (10.06 vs 1.83) were significantly greater for patients than for controls (each p <0.001). The circulating endothelial progenitor cell level correlated positively with the number of patient colonies (r = 0.762, p <0.001). Cells cultured from patients and controls showed a similar growth pattern, immunophenotype, ability to uptake Ac-LDL and bind lectin, and form capillary tubes in vitro. However, significantly more VEGF-R2(+) circulating endothelial progenitor cells were found in preparations from patients with renal cell carcinoma than from healthy controls (21.1% vs 13.4%, p <0.001). Earlier emergence of circulating endothelial progenitor cell colonies, a higher cell culture success rate and more colonies were found for patients with renal cell carcinoma than for healthy controls. Results

  7. Detergent solubilization of the EGF receptor from A431 cells

    NASA Technical Reports Server (NTRS)

    Dayanidhi, R.; Rintoul, D. A.; Spooner, B. S. (Principal Investigator)

    1993-01-01

    Functional reconstitution of purified preparations of human epidermal growth factor receptor (EGFR) requires dissociation of the protein from its plasma membrane lipid environment. Solubilization of membrane proteins in this manner requires the use of detergents, which are known to disrupt plasma membrane lipid/protein interactions. We have investigated the ability of three nonionic detergents to solubilize the human EGFR selectively, and have also analyzed the effect of these various treatments on the intrinsic tyrosyl kinase activity of the receptor. The nonionic detergent known as n-octyl glucoside (n-octyl beta-D-glucopyranoside) was found to give the best combination of selectivity, yield, and maintenance of enzymatic activity of the human EGFR.

  8. Molecular Genetic Evidence for a Common Clonal Origin of Urinary Bladder Small Cell Carcinoma and Coexisting Urothelial Carcinoma

    PubMed Central

    Cheng, Liang; Jones, Timothy D.; McCarthy, Ryan P.; Eble, John N.; Wang, Mingsheng; MacLennan, Gregory T.; Lopez-Beltran, Antonio; Yang, Ximing J.; Koch, Michael O.; Zhang, Shaobo; Pan, Chong-Xian; Baldridge, Lee Ann

    2005-01-01

    In most cases, small-cell carcinoma of the urinary bladder is admixed with other histological types of bladder carcinoma. To understand the pathogenetic relationship between the two tumor types, we analyzed histologically distinct tumor cell populations from the same patient for loss of heterozygosity (LOH) and X chromosome inactivation (in female patients). We examined five polymorphic microsatellite markers located on chromosome 3p25-26 (D3S3050), chromosome 9p21 (IFNA and D9S171), chromosome 9q32-33 (D9S177), and chromosome 17p13 (TP53) in 20 patients with small-cell carcinoma of the urinary bladder and concurrent urothelial carcinoma. DNA samples were prepared from formalin-fixed, paraffin-embedded tissue sections using laser-assisted microdissection. A nearly identical pattern of allelic loss was observed in the two tumor types in all cases, with an overall frequency of allelic loss of 90% (18 of 20 cases). Three patients showed different allelic loss patterns in the two tumor types at a single locus; however, the LOH patterns at the remaining loci were identical. Similarly, the same pattern of nonrandom X chromosome inactivation was present in both carcinoma components in the four cases analyzed. Concordant genetic alterations and X chromosome inactivation between small-cell carcinoma and coexisting urothelial carcinoma suggest that both tumor components originate from the same cells in the urothelium. PMID:15855652

  9. Fusobacterium nucleatum and T Cells in Colorectal Carcinoma.

    PubMed

    Mima, Kosuke; Sukawa, Yasutaka; Nishihara, Reiko; Qian, Zhi Rong; Yamauchi, Mai; Inamura, Kentaro; Kim, Sun A; Masuda, Atsuhiro; Nowak, Jonathan A; Nosho, Katsuhiko; Kostic, Aleksandar D; Giannakis, Marios; Watanabe, Hideo; Bullman, Susan; Milner, Danny A; Harris, Curtis C; Giovannucci, Edward; Garraway, Levi A; Freeman, Gordon J; Dranoff, Glenn; Chan, Andrew T; Garrett, Wendy S; Huttenhower, Curtis; Fuchs, Charles S; Ogino, Shuji

    2015-08-01

    Evidence indicates a complex link between gut microbiome, immunity, and intestinal tumorigenesis. To target the microbiota and immunity for colorectal cancer prevention and therapy, a better understanding of the relationship between microorganisms and immune cells in the tumor microenvironment is needed. Experimental evidence suggests that Fusobacterium nucleatum may promote colonic neoplasia development by downregulating antitumor T cell-mediated adaptive immunity. To test the hypothesis that a greater amount of F nucleatum in colorectal carcinoma tissue is associated with a lower density of T cells in tumor tissue. A cross-sectional analysis was conducted on 598 rectal and colon carcinoma cases in 2 US nationwide prospective cohort studies with follow-up through 2006, the Nurses' Health Study (participants enrolled in 1976) and the Health Professionals Follow-up Study (participants enrolled in 1986). Tissue collection and processing were performed from 2002 through 2008, and immunity assessment, 2008 through 2009. From 2013 through 2014, the amount of F nucleatum in colorectal carcinoma tissue was measured by quantitative polymerase chain reaction assay; we equally dichotomized positive cases (high vs low). Multivariable ordinal logistic regression analysis was conducted in 2014 to assess associations of the amount of F nucleatum with densities (quartiles) of T cells in tumor tissue, controlling for clinical and tumor molecular features, including microsatellite instability, CpG island methylator phenotype, long interspersed nucleotide element-1 (LINE-1) methylation, and KRAS, BRAF, and PIK3CA mutation status. We adjusted the 2-sided α level to .013 for multiple hypothesis testing. Densities of CD3+, CD8+, CD45RO (protein tyrosine phosphatase receptor type C [PTPRC])+, and FOXP3+ T cells in tumor tissue, determined by means of tissue microarray immunohistochemical analysis and computer-assisted image analysis. F nucleatum was detected in colorectal carcinoma

  10. Squamous Cell Cancer of The Lung with Synchronous Renal Cell Carcinoma

    PubMed Central

    Ateş, İhsan; Yazıcı, Ozan; Ateş, Hale; Yazılıtaş, Doğan; Özcan, Ayşe Naz; Ağaçkıran, Yetkin; Zengin, Nurullah

    2016-01-01

    Coexistence of two or more primary cancers is a relatively rare case. Not with standing that the coexistence of multiple primary cancers is often discussed in the literature, there is a small number of publications concerning the coexistence of squamous cell lung carcinoma and renal cancer. In this case report, detection of both squamous cell lung carcinoma and primary renal cancer in one male patient is going to be discussed. PMID:29404140

  11. NEDD 4 binding protein 2-like 1 promotes cancer cell invasion in oral squamous cell carcinoma.

    PubMed

    Sasahira, Tomonori; Kurihara, Miyako; Nishiguchi, Yukiko; Fujiwara, Rina; Kirita, Tadaaki; Kuniyasu, Hiroki

    2016-08-01

    Head and neck cancer, including oral squamous cell carcinoma, is the sixth most common cancer worldwide. Although cancer cell invasion and metastasis are crucial for tumor progression, detailed molecular mechanisms underlying the invasion and metastasis of oral squamous cell carcinoma are unclear. Comparison of transcriptional profiles using a cDNA microarray demonstrated that N4BP2L1, a novel oncogene expressed by neural precursor cells, is involved in oral squamous cell carcinoma. Expression of N4BP2L1 in oral squamous cell carcinoma is regulated by activation of miR-448 and is higher than in normal oral mucosa. Knockdown of N4BP2L1 and upregulation of miR-448 significantly reduced the invasive potential of oral squamous cell carcinoma cells. We studied N4BP2L1 expression in 187 cases of oral squamous cell carcinoma and found its overexpression to be significantly associated with nodal metastasis (P = 0.0155) and poor prognosis (P = 0.0136). Expression of miR-448 was found to be inversely associated with that of N4BP2L1 (P = 0.0019). Cox proportional hazards analysis identified N4BP2L1 expression as an independent predictor of disease-free survival (P = 0.0349). Our results suggest that N4BP2L1 plays an important role in tumor cell invasion in oral squamous cell carcinoma. Further studies on expression of N4BP2L1 may provide new insight into its function and clarify its potential as biomarker in human oral cancer.

  12. Diagnosis and therapy of oral squamous cell carcinoma.

    PubMed

    Konkimalla, V Badireenath; Suhas, Venkatramana Laxminarayana; Chandra, Nagasuma R; Gebhart, Erich; Efferth, Thomas

    2007-03-01

    Oral squamous cell carcinoma ranks among the top ten most common cancers worldwide. Despite the success in diagnosis and therapy during the past 30 years, oral squamous cell carcinoma still belongs to the tumor types with a very unfavorable prognosis. In an effort to identify genomic alterations with prognostic relevance, we applied the comparative genomic hybridization technique on oral squamous cell carcinoma. The tumors exhibited from five up to 47 DNA copy number alterations, indicating a considerable degree of genomic imbalance. Out of 35 tumors, 19 showed a gain of chromosome band 7p12. Genomic imbalances were investigated by hierarchical cluster analysis and clustered image mapping to investigate whether genomic profiles correlate with clinical data. Results of the present investigation show that profiling of genomic imbalances in general, and especially of the epidermal growth factor receptor (EGFR) on 7p12, may be suitable as prognostic factors. In order to identify small-molecule inhibitors for EGFR, we established a database of 531 natural compounds derived from medicinal plants used in traditional Chinese medicine. Candidate compounds were identified by correlation analysis using the Kendall tau-test of IC50 values of tumor cell lines and microarray-based EGFR mRNA expression. Further validation was performed by molecular docking studies using the AutoDock program with the crystal structure of EGFR tyrosine kinase domain as docking template. We estimate these results will be a further step toward the ultimate goal of individualized, patient-adapted tumor treatment based on tumor molecular profiling.

  13. Different effects of H2O2 treatment on cervical squamous carcinoma cells and adenocarcinoma cells

    PubMed Central

    Zhang, Peihai; Yin, Haiqin; Wang, Sie; Wei, Yuping; Peng, Nan

    2015-01-01

    Introduction This study aims to compare the antioxidant abilities of cervical squamous carcinoma cells and cervical adenocarcinoma cells and to study the related mechanisms. Material and methods Cervical squamous carcinoma and adenocarcinoma cells were treated with H2O2. Cell proliferation was determined with the MTT assay. The reactive oxygen species (ROS) level was detected by the 2’,7’-dichlorofluorescein-diacetate (DCFH-DA) method. The 5,5’-dithiobis-2-nitrobenzoic acid (DTNB) method was performed to measure intracellular concentrations of reduced glutathione (GSH) and oxidized glutathione (GSSG). The nitrite formation method, the molybdate colorimetric method, and the DTNB colorimetric method were used to determine activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), respectively. Results Compared with untreated control cells, cell proliferation of cervical squamous carcinoma cells and cervical adenocarcinoma cells was significantly inhibited by H2O2 treatment (p < 0.05). Reactive oxygen species levels and GSSG levels were significantly increased (p < 0.01), whereas GSH levels were significantly decreased (p < 0.05 or 0.01) in both cells after H2O2 treatment. Thus the ratio of GSH/GSSG was significantly decreased by H2O2 treatment in both cells (p < 0.01). In addition, H2O2 treatment significantly increased activities of SOD, CAT, and GPx in both cells (p < 0.05 or 0.01). Furthermore, the above-mentioned changes induced by H2O2 treatment were more dramatic in cervical squamous carcinoma cells. Conclusions The antioxidant ability of cervical squamous carcinoma cells is lower than that of cervical adenocarcinoma cells, which may be related to the increased ROS levels in cervical squamous carcinoma cells induced by H2O2 treatments. PMID:26788095

  14. Advances on immunotherapy in genitourinary and renal cell carcinoma

    PubMed Central

    Botta, Gregory P.; Granowicz, Eric; Costantini, Carrie

    2017-01-01

    Genitourinary (GU) cancers are a group of epithelial malignancies associated with the organs involved in the excretion of urine. Renal cell, urothelial, and prostatic carcinoma are the overwhelming subtypes diagnosed by oncologists. Each of these was traditionally treated surgically when local and non-invasive. When these carcinomas spread, invade, or metastasize, surgical control lacks in efficacy. Chemotherapeutic regimens have been implemented for decades and have increased overall survival but many patients progress. Molecular targeting through tyrosine kinase inhibition of the vascular endothelial growth factor (VEGF) has emerged as a frontline therapy in kidney cancer with more durable responses. More recently, immunotherapy has begun to find efficacy in many other solid tumors including melanoma and non-small cell lung cancer. The inherent genetic instability of this group of cancers makes them ideal solid tumors for immune modulation. Vaccines manufactured to initiate T-Cell regulation through neoplastic-antigen presentation are available for prostate cancer and are currently on trial in renal cell carcinoma (RCC). Programmed death-1 (PD-1) and its ligand (PD-L1) are intricate members of cellular immunity against neoplastic cells. In an activated, unbound state, these molecules permit T-cell activation and cytotoxic killing of cancer cells. However, when they are linked, cellular immunity is attenuated and local cancer cells are permitted the opportunity to proliferate and invade. A novel class of monoclonal antibodies have been developed which stop PD-1 linkage and thus uncouple the ‘stop’ signal of these neoplastic regulatory cells. The increased overall and progression free survival have made them attractive options alone as well as in combination with anti-VEGF inhibitors for patients. Although more tolerable than chemotherapy, immunotherapeutics have adverse potential toxicities. Overall, the use of immunomodulatory medications have opened a new

  15. Notch signaling is significantly suppressed in basal cell carcinomas and activation induces basal cell carcinoma cell apoptosis.

    PubMed

    Shi, Feng-Tao; Yu, Mei; Zloty, David; Bell, Robert H; Wang, Eddy; Akhoundsadegh, Noushin; Leung, Gigi; Haegert, Anne; Carr, Nicholas; Shapiro, Jerry; McElwee, Kevin J

    2017-04-01

    A subset of basal cell carcinomas (BCCs) are directly derived from hair follicles (HFs). In some respects, HFs can be defined as 'ordered' skin appendage growths, while BCCs can be regarded as 'disordered' skin appendage growths. The aim of the present study was to examine HFs and BCCs to define the expression of common and unique signaling pathways in each skin appendage. Human nodular BCCs, along with HFs and non‑follicular skin epithelium from normal individuals, were examined using microarrays, qPCR, and immunohistochemistry. Subsequently, BCC cells and root sheath keratinocyte cells from HFs were cultured and treated with Notch signaling peptide Jagged1 (JAG1). Gene expression, protein levels, and cell apoptosis susceptibility were assessed using qPCR, immunoblotting, and flow cytometry, respectively. Specific molecular mechanisms were found to be involved in the process of cell self‑renewal in the HFs and BCCs, including Notch and Hedgehog signaling pathways. However, several key Notch signaling factors showed significant differential expression in BCCs compared with HFs. Stimulating Notch signaling with JAG1 induced apoptosis of BCC cells by increasing Fas ligand expression and downstream caspase-8 activation. The present study showed that Notch signaling pathway activity is suppressed in BCCs, and is highly expressed in HFs. Elements of the Notch pathway could, therefore, represent targets for the treatment of BCCs and potentially in hair follicle engineering.

  16. Cutaneous and laryngeal squamous cell carcinoma in mixed epidermolysis bullosa, kindler syndrome.

    PubMed

    Mizutani, Hiromi; Masuda, Koji; Nakamura, Naomi; Takenaka, Hideya; Tsuruta, Daisuke; Katoh, Norito

    2012-05-01

    Kindler syndrome is a rare autosomal recessive genodermatosis characterized by trauma-induced acral blisters in infancy and childhood, photosensitivity, and progressive poikiloderma. Other clinical features include chronic erosive gingivitis, dysphagia, esophageal and urethral strictures, ectropion, and an increased risk of mucocutaneous squamous cell carcinoma. We describe a patient with Kindler syndrome associated with squamous cell carcinoma of the skin and larynx. He had squamous cell carcinoma on his left knee with simultaneous unresectable laryngeal carcinoma at the age of 43 years. The squamous cell carcinoma on his knee was excised and the laryngeal carcinoma was treated with radiation therapy. Although pathophysiology of Kindler syndrome and its frequency of association with cancer are still not fully elucidated, we speculate that long-term erosion and regeneration of mucosal and cutaneous surfaces may have induced squamous cell carcinoma on the patient's knee and larynx.

  17. Squamous cell carcinoma of the lung with highly proliferating fibromatosis-like stroma: a rare phenomenon.

    PubMed

    Tajima, Shogo; Takanashi, Yusuke; Koda, Kenji

    2015-01-01

    Few cases of carcinoma with exuberant stromal proliferation have been documented, apart from scirrhous carcinoma. To the best of our knowledge, previous cases of carcinoma exhibiting exuberant stromal proliferation have exclusively been reported in the thyroid gland, specifically as papillary carcinoma. The exuberant stromal proliferation has been recognized to be similar to either fibromatosis or nodular fasciitis. Herein, we report a case of a 74-year-old Japanese man whose tumor in the upper lobe of his right lung displayed highly proliferating stroma with dispersed, poorly differentiated squamous cell carcinoma nests. The stromal spindle cells (fibroblasts/myofibroblasts) had similar molecular profiles to those typically observed in fibromatosis rather than nodular fasciitis, resulting in the designation of "fibromatosis-like" stroma. The presence of carcinoma cells, along with stromal cells, expressing TGF-β in this case likely fostered continuous stromal proliferation, presumably in conjunction with the unique microenvironment in which the carcinoma cells were present.

  18. Classification of human carcinoma cells using multispectral imagery

    NASA Astrophysics Data System (ADS)

    Ćinar, Umut; Y. Ćetin, Yasemin; Ćetin-Atalay, Rengul; Ćetin, Enis

    2016-03-01

    In this paper, we present a technique for automatically classifying human carcinoma cell images using textural features. An image dataset containing microscopy biopsy images from different patients for 14 distinct cancer cell line type is studied. The images are captured using a RGB camera attached to an inverted microscopy device. Texture based Gabor features are extracted from multispectral input images. SVM classifier is used to generate a descriptive model for the purpose of cell line classification. The experimental results depict satisfactory performance, and the proposed method is versatile for various microscopy magnification options.

  19. Clear cell hepatocellular carcinoma: Back to the basics for diagnosis.

    PubMed

    Sakhuja, Puja; Mishra, Pramod K; Rajesh, R; Sharma, Ashok Kumar; Gondal, Ranjana; Singh, Meeta

    2015-01-01

    Hepatocellular carcinoma (HCC) is a common cancer world-wide with a higher incidence in Asia. Clear cell variant of HCC (CCHCC) has a frequency ranging from 0.4% to 37%. The presence of 90-100% clear cells is rare. In the present case, a 35-year-old female patient presented with fever and a large abdominal mass in the right hypochondrium. Histology of the tumor revealed >95% clear cells and after taking multiple sections from different areas of tumor only few scattered cells with eosinophilic cytoplasm were found. Immunohistochemistry with Hep Par 1, Glypican 3 and polyclonal carcinoembryonic antigen were negative as were all other markers for metastatic clear cell tumors. Histological diagnosis was based on routine H and E sections showing a histological pattern of architecture with thickened trabeculae. We describe a rare case of CCHCC with >95% clear cells and no immunoreactivity in tumor cells in a non-cirrhotic liver.

  20. Personalized targeted therapy for esophageal squamous cell carcinoma

    PubMed Central

    Kang, Xiaozheng; Chen, Keneng; Li, Yicheng; Li, Jianying; D'Amico, Thomas A; Chen, Xiaoxin

    2015-01-01

    Esophageal squamous cell carcinoma continues to heavily burden clinicians worldwide. Researchers have discovered the genomic landscape of esophageal squamous cell carcinoma, which holds promise for an era of personalized oncology care. One of the most pressing problems facing this issue is to improve the understanding of the newly available genomic data, and identify the driver-gene mutations, pathways, and networks. The emergence of a legion of novel targeted agents has generated much hope and hype regarding more potent treatment regimens, but the accuracy of drug selection is still arguable. Other problems, such as cancer heterogeneity, drug resistance, exceptional responders, and side effects, have to be surmounted. Evolving topics in personalized oncology, such as interpretation of genomics data, issues in targeted therapy, research approaches for targeted therapy, and future perspectives, will be discussed in this editorial. PMID:26167067

  1. Focal cutaneous squamous cell carcinoma following radium-223 extravasation.

    PubMed

    Benjegerdes, Katie E; Brown, Shannon C; Housewright, Chad D

    2017-01-01

    Long-term sequelae due to extravasation of intravenous radioisotopes resulting in radiation injuries are rarely reported. As the use of radioactive isotopes for the treatment of osteoblastic metastases increases, information regarding the prevention, treatment, and long-term monitoring of suspected extravasation injury will become increasingly important. We present a patient with no previous history of skin cancer who developed an aggressive cutaneous squamous cell carcinoma at the site of prior radium-223 extravasation. We recommend that patients who experience extravasation of therapeutic radioisotopes be monitored by dermatologists for long-term sequelae. Cutaneous squamous cell carcinoma should be recognized as a rare but potential adverse event following cutaneous extravasation of radium-223 and is likely a side effect that is severely underreported.

  2. Nevoid basal cell carcinoma syndrome (Gorlin-Goltz syndrome)

    PubMed Central

    Kiran, N. K.; Tilak Raj, T. N.; Mukunda, K. S.; Rajashekar Reddy, V.

    2012-01-01

    The Gorlin-Goltz syndrome, also known as nevoid basal cell carcinoma syndrome (NBCCS), is an infrequent multisystemic disease inherited in a dominant autosomal way, which shows a high level of penetrance and variable expressiveness. It is characterized by odontogenic keratocysts in the jaw, multiple basal cell nevi carcinomas and skeletal abnormalities. This syndrome may be diagnosed early by a dentist by routine radiographic exams in the first decade of life, since the odontogenic keratocysts are usually one of the first manifestations of the syndrome. This case report presents a patient diagnosed as NBCCS by clinical, radiographic and histological findings in a 13-year-old boy. This paper highlights the importance of early diagnosis of NBCCS which can help in preventive multidisciplinary approach to provide a better prognosis for the patient. PMID:23633824

  3. Nevoid basal cell carcinoma syndrome (Gorlin-Goltz syndrome).

    PubMed

    Kiran, N K; Tilak Raj, T N; Mukunda, K S; Rajashekar Reddy, V

    2012-10-01

    The Gorlin-Goltz syndrome, also known as nevoid basal cell carcinoma syndrome (NBCCS), is an infrequent multisystemic disease inherited in a dominant autosomal way, which shows a high level of penetrance and variable expressiveness. It is characterized by odontogenic keratocysts in the jaw, multiple basal cell nevi carcinomas and skeletal abnormalities. This syndrome may be diagnosed early by a dentist by routine radiographic exams in the first decade of life, since the odontogenic keratocysts are usually one of the first manifestations of the syndrome. This case report presents a patient diagnosed as NBCCS by clinical, radiographic and histological findings in a 13-year-old boy. This paper highlights the importance of early diagnosis of NBCCS which can help in preventive multidisciplinary approach to provide a better prognosis for the patient.

  4. Giant kidney worms in a patient with renal cell carcinoma.

    PubMed

    Kuehn, Jemima; Lombardo, Lindsay; Janda, William M; Hollowell, Courtney M P

    2016-03-07

    Dioctophyma renale (D. renale), or giant kidney worms, are the largest nematodes that infect mammals. Approximately 20 cases of human infection have been reported. We present a case of a 71-year-old man with a recent history of unintentional weight loss and painless haematuria, passing elongated erythematous tissue via his urethra. CT revealed a left renal mass with pulmonary nodules and hepatic lesions. On microscopy, the erythematous tissue passed was identified as D. renale. On subsequent renal biopsy, pathology was consistent with renal cell carcinoma. This is the first reported case of concomitant D. renale infection and renal cell carcinoma, and the second reported case of D. renale infection of the left kidney alone. 2016 BMJ Publishing Group Ltd.

  5. Giant kidney worms in a patient with renal cell carcinoma

    PubMed Central

    Kuehn, Jemima; Lombardo, Lindsay; Janda, William M; Hollowell, Courtney M P

    2016-01-01

    Dioctophyma renale (D. renale), or giant kidney worms, are the largest nematodes that infect mammals. Approximately 20 cases of human infection have been reported. We present a case of a 71-year-old man with a recent history of unintentional weight loss and painless haematuria, passing elongated erythematous tissue via his urethra. CT revealed a left renal mass with pulmonary nodules and hepatic lesions. On microscopy, the erythematous tissue passed was identified as D. renale. On subsequent renal biopsy, pathology was consistent with renal cell carcinoma. This is the first reported case of concomitant D. renale infection and renal cell carcinoma, and the second reported case of D. renale infection of the left kidney alone. PMID:26952087

  6. [Metastatic signet ring cell carcinoma to the breast from stomach].

    PubMed

    Krichen Makni, S; Abbes, K; Khanfir, A; Frikha, M; Sellami Boudawara, T

    2007-09-01

    Metastatic tumors in the breast are quite rare and constitute 0.5 to 6% of all breast malignancies. They often occur in a polymetastatic context. The most frequent primitive tumors are lymphoma, leukaemia and malignant melanoma. The gastric origin is seldom reported. We report here the observation of a 40-years woman operated in urgency for an acute abdominal syndrome. A gastric tumor was discovered intraoperatively with ovarian metastasis and peritoneal carcinosis. The pathological examination revealed a gastric signet ring cell carcinoma with an infiltration of the right ovary. Four months later, the patient presented with a lump of the right breast. The histologic examination corresponded to a mammary metastasis by a signet ring cell carcinoma from stomach. The objective of our work is to discuss through this observation the anatomoclinical and evolutionary characteristics of breast metastasis.

  7. Multimodal confocal mosaicing microscopy: an emphasis on squamous cell carcinoma

    NASA Astrophysics Data System (ADS)

    Chen, Nathaniel W.; Sensibaugh, Jordan; Ardeshiri, Ardaland; Blanchard, Adam; Jacques, Steven; Gareau, Daniel

    2010-02-01

    Our previous study reported a sensitivity of 96.6% and a specificity of 89.2% in rapidly detecting Basal Cell Carcinomas (BCCs) when nuclei were stained with acridine orange. Squamous Cell Carcinomas (SCCs) and infiltrative BCCs remain difficult to detect. More complete screening can be achieved utilizing both acridine orange for nuclei staining and eosin for cytoplasmic contrast, using two lasers to excite the two stains independently. Nuclear fluorescence is achieved by staining with acridine orange (0.5mM, 60 s), and cytoplasmic fluorescence is achieved by staining with eosin working solution (30 s). This work shows good morphological contrast of SCC and infiltrative BCC with eosin, acridine orange, and reflectance, and presents a means for rapid SCC and infiltrative BCC detection in fresh skin excisions using multimodal confocal microscopy. In addition, digital staining is shown to effectively simulate hematoxylin and eosin (H&E) histology with confocal mosaics.

  8. Cutaneous Squamous Cell Carcinoma of the Head and Neck

    PubMed Central

    Gurudutt, Vivek V.; Genden, Eric M.

    2011-01-01

    Cutaneous squamous cell carcinoma of the head and neck is an epidemic that reaches all parts of the world. Making the diagnosis relies on the acumen of the clinician and pathologist. Various pathologic subtypes exist and differ in histology and prognosis. High-risk tumors need aggressive treatment and vigilant surveillance to monitor for recurrence. Large tumors, deep tissue invasion, perineural involvement, recurrence, location in high-risk areas, and immunosuppression are implicated in worsening prognosis. Surgery is the mainstay of treatment with adjuvant radiation therapy as needed for aggressive tumors; however, other modalities are potentially useful for low-risk lesions. The use of Mohs surgery has become increasingly useful and has shown high success rates. Involvement of parotid and neck lymph nodes significantly affects outcomes and the physician should be comfortable with management of this complex disease. This paper examines the diagnosis, pathology, clinical course, and treatment options for cutaneous squamous cell carcinoma of the head and neck. PMID:21461387

  9. Breast Metastatic Localization of Signet-Ring Cell Gastric Carcinoma

    PubMed Central

    Parrell Soler, C.; Palacios Marqués, A.; Saco López, L.; Bermejo De las Heras, R.; Pertusa Martínez, S.

    2011-01-01

    Metastatic tumors in the breast are quite rare and constitute 0,5 to 6% of all breast malignancies. They often occur in a polymetastatic context. Gastrointestinal lesions rarely metastasize to the breast. The first case of a metastasis deposit to the breast and ovary from gastric signet-ring cell carcinoma was reported in the literature in 1999. Since this report, only 5 cases have been reported. We present a case report of a 37-year-old woman who complained of a lump in the left breast. Two months earlier, the woman underwent a subtotal gastrectomy and a total hysterectomy with double anexectomy, which histologically was diagnosed of gastric signet-ring carcinoma, disseminated with Krukenberg's tumor. In those days, the patient was following a chemotherapy treatment. A core needle biopsy of the lesion in left breast revealed cells with signet-ring features, with probably gastric origin. PMID:21637360

  10. Giant Cornu Cutaneum Superimposed on Basal Cell Carcinoma.

    PubMed

    Agirgol, S; Mansur, A T; Bozkurt, K; Azakli, H N; Babacan, A; Dikmen, A

    2015-09-01

    Cornu cutaneum (CC) is a clinical term that describes the horn-like keratotic lesions extending vertically from the skin. Benign, premalignant or malignant lesions may be present at the base of CC. Seborrhoeic keratosis and squamous cell carcinoma (SCC) are the most commonly reported benign and malignant forms, respectively. Basal cell carcinoma (BCC) at the base is rare. Here, we report on an 85-year old female patient having multiple CC lesions, one being giant on her face and two of the lesions diagnosed with BCC at the base. This case is of significance due to the presence of giant and multiple CC and detection of BCC at the base of more than one lesion. This present case indicates the need for the treatment of possible malignant lesions underlying CC in the elderly by total surgical excision.

  11. Uroplakins, specific membrane proteins of urothelial umbrella cells, as histological markers of metastatic transitional cell carcinomas.

    PubMed Central

    Moll, R.; Wu, X. R.; Lin, J. H.; Sun, T. T.

    1995-01-01

    Uroplakins (UPs) Ia, Ib, II, and III, transmembrane proteins constituting the asymmetrical unit membrane of urothelial umbrella cells, are the first specific urothelial differentiation markers described. We investigated the presence and localization patterns of UPs in various human carcinomas by applying immunohistochemistry (avidin-biotin-peroxidase complex method), using rabbit antibodies against UPs II and III, to paraffin sections. Positive reactions for UP III (sometimes very focal) were noted in 14 of the 16 papillary noninvasive transitional cell carcinomas (TCCs) (88%), 29 of the 55 invasive TCCs (53%), and 23 of the 35 TCC metastases (66%). Different localization patterns of UPs could be distinguished, including superficial membrane staining like that found in normal umbrella cells (in papillary carcinoma), luminal (microluminal) membrane staining (in papillary and invasive carcinoma), and, against expectations, peripheral membrane staining (in invasive carcinoma). Non-TCC carcinomas of various origins (n = 177) were consistently negative for UPs. The presence of UPs in metastatic TCCs represents a prime example of even advanced tumor progression being compatible with the (focal) expression of highly specialized differentiation repertoires. Although of only medium-grade sensitivity, UPs do seem to be highly specific urothelial lineage markers, thus operating up interesting histodiagnostic possibilities in cases of carcinoma metastases of uncertain origin. Images Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 PMID:7485401

  12. Pedunculated and Telangiectatic Merkel Cell Carcinoma: An Unusual Clinical Presentation

    PubMed Central

    Errichetti, Enzo; Piccirillo, Angelo; Ricciuti, Federico; Ricciuti, Francesco

    2013-01-01

    Merkel cell carcinoma (MCC) is an uncommon aggressive neuroendocrine tumor of the skin that classically presents on chronic sun-damaged skin as a skin-colored, red or violaceous, firm and nontender papule or nodule with a smooth and shiny surface. Ulcerations can be observed very seldom and only in very advanced lesions. We present a unique case of a MCC presenting with two unusual clinical features: The Telangiectatic surface and the pedunculated aspect. PMID:23723504

  13. Pedunculated and telangiectatic merkel cell carcinoma: an unusual clinical presentation.

    PubMed

    Errichetti, Enzo; Piccirillo, Angelo; Ricciuti, Federico; Ricciuti, Francesco

    2013-05-01

    Merkel cell carcinoma (MCC) is an uncommon aggressive neuroendocrine tumor of the skin that classically presents on chronic sun-damaged skin as a skin-colored, red or violaceous, firm and nontender papule or nodule with a smooth and shiny surface. Ulcerations can be observed very seldom and only in very advanced lesions. We present a unique case of a MCC presenting with two unusual clinical features: The Telangiectatic surface and the pedunculated aspect.

  14. Imaging and Management of Intrathoracic Renal Cell Carcinoma Metastases.

    PubMed

    Price, Melissa; Wu, Carol C; Genshaft, Scott; Sadow, Peter M; Xie, Ling; Shepard, Jo-Anne O; McDermott, Shaunagh

    2018-06-01

    Renal cell carcinoma (RCC) has a propensity to metastasize to the chest, with the lungs being the most common distant metastatic site. The histologic subtype of RCC has implications for prognosis. Significant advances have been made in the management of metastatic RCC, both in systemic and locoregional therapies. The aim of this article is to review appearances of intrathoracic metastases from RCC and to discuss treatment considerations.

  15. Bone pulsating metastasis due to renal cell carcinoma.

    PubMed

    Cınar, Murat; Derincek, Alihan; Karan, Belgin; Akpınar, Sercan; Tuncay, Cengiz

    2010-11-01

    Pulsation on the bone cortex surface is a rare condition. Pulsative palpation of the superficial-located bone tumors can be misperceived as an aneurysm. Fifty-eight-year-old man is presented with pulsating bone mass in his proximal tibia. During angiographic examination, hypervascular masses were diagnosed both at right kidney and at right proximal tibia. Renal cell carcinoma was diagnosed after abdominal CT scan. Proximal tibia biopsy was complicated with projectile bleeding.

  16. New York esophageal squamous cell carcinoma-1 and cancer immunotherapy.

    PubMed

    Esfandiary, Ali; Ghafouri-Fard, Soudeh

    2015-01-01

    New York esophageal squamous cell carcinoma 1 (NY-ESO-1) is a known cancer testis gene with exceptional immunogenicity and prevalent expression in many cancer types. These characteristics have made it an appropriate vaccine candidate with the potential application against various malignancies. This article reviews recent knowledge about the NY-ESO-1 biology, function, immunogenicity and expression in cancers as well as and the results of clinical trials with this antigen.

  17. Clinicopathologic Features of Submucosal Esophageal Squamous Cell Carcinoma.

    PubMed

    Emi, Manabu; Hihara, Jun; Hamai, Yoichi; Furukawa, Takaoki; Ibuki, Yuta; Okada, Morihito

    2017-12-01

    The prognoses of submucosal esophageal squamous cell carcinoma patients vary. Patients with favorable prognoses may receive less invasive or nonsurgical interventions, whereas patients with poor prognoses or advanced esophageal cancer may require aggressive treatments. We sought to identify prognostic factors for patients with submucosal esophageal squamous cell carcinoma, focusing on lymph node metastasis and recurrence. We included 137 submucosal esophageal squamous cell carcinoma patients who had undergone transthoracic esophagectomy with systematic extended lymph node dissection. Submucosal tumors were classified as SM1, SM2, and SM3 according to the depth of invasion. Prognostic factors were determined by univariable and multivariable analyses. Lymph node metastasis was observed in 18.8%, 30.5%, and 50.0% of SM1, SM2, and SM3 cases, respectively. The overall 5-year recurrence rate was 21.9%; the rates for SM1, SM2, and SM3 tumors were 9.4%, 18.6%, and 34.8%, respectively. The SM1 tumors all recurred locoregionally; distant metastasis occurred in SM2 and SM3 cases. The 5-year overall survival rates were 83%, 77%, and 59% for SM1, SM2, and SM3 cases, respectively. On univariable analysis, lymph node metastasis, depth of submucosal invasion (SM3 versus SM1/2), and tumor location (upper thoracic versus mid/lower thoracic) were poor prognostic factors for overall survival. Multivariable Cox regression analyses identified depth of submucosal invasion (hazard ratio 2.51, 95% confidence interval: 1.37 to 4.61) and tumor location (hazard ratio 2.43, 95% confidence interval: 1.18 to 4.63) as preoperative prognostic factors. Tumor location (upper thoracic) and infiltration (SM3) are the worse prognostic factors of submucosal esophageal squamous cell carcinoma, but lymph node metastasis is not a predictor of poorer prognosis. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  18. Autofluorescence imaging of basal cell carcinoma by smartphone RGB camera.

    PubMed

    Lihachev, Alexey; Derjabo, Alexander; Ferulova, Inesa; Lange, Marta; Lihacova, Ilze; Spigulis, Janis

    2015-01-01

    The feasibility of smartphones for in vivo skin autofluorescence imaging has been investigated. Filtered autofluorescence images from the same tissue area were periodically captured by a smartphone RGB camera with subsequent detection of fluorescence intensity decreasing at each image pixel for further imaging the planar distribution of those values. The proposed methodology was tested clinically with 13 basal cell carcinoma and 1 atypical nevus. Several clinical cases and potential future applications of the smartphone-based technique are discussed.

  19. Autofluorescence imaging of basal cell carcinoma by smartphone RGB camera

    NASA Astrophysics Data System (ADS)

    Lihachev, Alexey; Derjabo, Alexander; Ferulova, Inesa; Lange, Marta; Lihacova, Ilze; Spigulis, Janis

    2015-12-01

    The feasibility of smartphones for in vivo skin autofluorescence imaging has been investigated. Filtered autofluorescence images from the same tissue area were periodically captured by a smartphone RGB camera with subsequent detection of fluorescence intensity decreasing at each image pixel for further imaging the planar distribution of those values. The proposed methodology was tested clinically with 13 basal cell carcinoma and 1 atypical nevus. Several clinical cases and potential future applications of the smartphone-based technique are discussed.

  20. Salvage Surgery for Locoregional Failure in Anal Squamous Cell Carcinoma.

    PubMed

    Guerra, Glen R; Kong, Joseph C; Bernardi, Maria-Pia; Ramsay, Robert G; Phillips, Wayne A; Warrier, Satish K; Lynch, A Craig; Ngan, Samuel Y; Heriot, Alexander G

    2018-02-01

    Anal squamous cell carcinoma is a rare cancer with a high cure rate, making research into the treatment of locoregional failure difficult. The purpose of this study was to examine factors related to local treatment failure and determine the outcomes of patients undergoing local salvage resection. This was a retrospective cohort study. This study was conducted at a quaternary referral center. Patients with anal squamous cell carcinoma treated with chemoradiotherapy between January 1983 and December 2015 were included. The influence of patient-, tumor-, and treatment-related factors on the primary outcome measures of locoregional failure, overall survival, and disease-free survival were investigated. Of 467 patients with anal squamous cell carcinoma, 63 experienced locoregional failure with 41 undergoing salvage resection. Twenty-seven patients (38%) had persistent disease and 36 (62%) developed locoregional recurrence. Multivariate analysis identified tumor stage (HR, 3.16; p < 0.002) as an independent predictor of locoregional failure. Thirty abdominoperineal resections and 11 pelvic exenterations were undertaken with no surgical mortality. At a median follow-up of 20 months (range, 4-150 months), 5-year overall and disease-free survival for the salvage cohort was 51% and 47%. Margin positivity was an independent predictor for relapse post-salvage surgery on multivariate analysis (HR, 20.1; p = 0.027). Nineteen patients (48%) developed further relapse, which included all 10 patients with a positive resection margin, 3 of whom underwent re-resection. Of the 19 patients with relapse, 3 remain alive and 2 have persistent disease. Limitations include the retrospective nature of the database, the prolonged time period of the study, and episodes of incomplete data. Advanced T stage is an independent predictor of local failure in anal squamous cell carcinoma. Most patients can be salvaged, with a positive resection margin being a strong predictor of further relapse and

  1. Effects of demethoxycurcumin on the viability and apoptosis of skin cancer cells.

    PubMed

    Wu, Yaoqun; Zhang, Pei; Yang, Hongyun; Ge, Yong; Xin, Yong

    2017-07-01

    The present study investigated the effects and mechanisms of demethoxycurcumin (DMC) on a human skin squamous cell carcinoma cell line, A431, and a human keratinocyte cell line, HaCaT. A431 and HaCaT cells were cultured in vitro. The effects of DMC treatment on cell viability were analyzed using the Cell Counting kit‑8 (CCK‑8) assay; cell cycle distribution was analyzed by flow cytometry; apoptosis was assessed by flow cytometry and Hoechst 33258 staining; and the protein expression levels of cytochrome c, B‑cell lymphoma 2 (Bcl‑2), Bcl‑2‑associated X protein (BAX), caspase‑9 and caspase‑3 were evaluated by western blotting. CCK‑8 assay results demonstrated that DMC treatment significantly inhibited viability of A431 and HaCaT cells in a dose‑dependent manner. Flow cytometric analysis confirmed that DMC treatment induced apoptosis in a dose‑dependent manner, and significantly increased the proportion of cells in G2/M phase. Western blot analysis indicated that the protein expression levels of Bcl‑2 were decreased, whereas the expression levels of BAX, caspase‑9, caspase‑3 and cytochrome c were increased following DMC treatment compared with in untreated cells. In conclusion, DMC treatment significantly inhibited viability of A431 and HaCaT cells, and induced cell cycle arrest in G2/M phase. The present study indicated that DMC may induce apoptosis of skin cancer cells through a caspase‑dependent pathway.

  2. Immunotherapy for pulmonary squamous cell carcinoma and colon carcinoma with pembrolizumab: A case report.

    PubMed

    Nozawa, Yoshihiro; Oka, Yuka; Oosugi, Jun; Takemura, Shinichi

    2018-05-01

    Novel treatment strategies such as immunotherapy are being evaluated to further improve the outcomes of colorectal cancer patients. To our knowledge, this is the first report to show both the successful treatment of pulmonary squamous cell carcinoma (SCC) with pembrolizumab alongside histological and immunohistochemical findings of resected colon cancer under immunotherapy for lung cancer. This patient was a 70-year-old man who presented with a right lung tumor and simultaneous adenocarcinoma of the sigmoid colon. Biopsy examination revealed squamous cell carcinoma in the right lung and adenocarcinoma of the sigmoid colon. The patient underwent successful pembrolizumab treatment as first-line immunotherapy for lung cancer, as demonstrated by computed tomography, and the sigmoid colon tumor was excised during an immunotherapy-free window. No unusual tumor growth in the right lung or abnormal abdominal signs was observed during the 9-month follow-up. Microscopically, the resected colon cancer specimen was characterized by numerous lymphoid cells in the partial stroma, with a large number of infiltrating lymphocytes consisting of CD3+, CD8+ T cells. In summary, this case demonstrates how immunotherapy affects PD-L1-negative colon cancer and indicates future treatment prospects.

  3. Invasive squamous cell carcinoma originating from a giant penile condyloma.

    PubMed

    Sir, Emin; Gungor, Melike; Ucer, Oktay; Kebat, Tulu

    2017-05-01

    In this case study, we present an unusual case with squamous cell carcinoma originating from a giant condyloma acuminata completely surrounding the penis. A 57-year-old circumcised heterosexual male patient presented with a penile lesion existing for 20 years. Incisional biopsy revealed acanthosis of the squamous epithelium. The patient was operated on under spinal anaesthesia. The lesion was resected circumferentially with macroscopic clearance, resulting in complete degloving of the penile shaft. Neurovascular bundles were preserved. The penile skin was constructed with a split thickness skin graft. Histopathological analysis of the lesion revealed an invasive and well-differentiated squamous cell carcinoma arising on a condyloma, and the surgical margins were free from tumour. The patient was staged as G2 T1 N0 M0 and was followed for one year. He did not have any erectile dysfunction and could engage in intercourse. Pelvic tomographic and physical examination findings did not reveal any episode of recurrence or metastasis. When encountering patients with giant condyloma acuminata, it should not be forgotten that it may be accompanied by squamous cell carcinoma. In addition, tissue excision should be as extensive as possible while keeping in mind the importance of the function. This is the first case of a penile-degloving surgery for giant penile condyloma, supporting conservative and preserving penile surgery for such tumours.

  4. Basal Cell Carcinoma Arising in a Breast Augmentation Scar.

    PubMed

    Edwards, Lisa R; Cresce, Nicole D; Russell, Mark A

    2017-04-01

    We report a case of a 46-year-old female who presented with a persistent lesion on the inferior right breast. The lesion was located within the scar from a breast augmentation procedure 12 years ago. The lesion had been treated as several conditions with no improvement. Biopsy revealed a superficial and nodular basal cell carcinoma, and the lesion was successfully removed with Mohs micrographic surgery. Basal cell carcinoma arising in a surgical scar is exceedingly rare with only 13 reported cases to date. This is the first reported case of basal cell carcinoma arising in a breast augmentation scar. We emphasize the importance of biopsy for suspicious lesions or those refractory to treatment, particularly those lesions that form within a scar. Level of Evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

  5. 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

  6. Vorinostat, an HDAC inhibitor attenuates epidermoid squamous cell carcinoma growth by dampening mTOR signaling pathway in a human xenograft murine model

    SciTech Connect

    Kurundkar, Deepali; Srivastava, Ritesh K.; Chaudhary, Sandeep C.

    Histone deacetylase (HDAC) inhibitors are potent anticancer agents and show efficacy against various human neoplasms. Vorinostat is a potent HDAC inhibitor and has shown potential to inhibit growth of human xenograft tumors. However, its effect on the growth of skin neoplasm remains undefined. In this study, we show that vorinostat (2 μM) reduced expression of HDAC1, 2, 3, and 7 in epidermoid carcinoma A431 cells. Consistently, it increased acetylation of histone H3 and p53. Vorinostat (100 mg/kg body weight, IP) treatment reduced human xenograft tumor growth in highly immunosuppressed nu/nu mice. Histologically, the vorinostat-treated tumor showed features of well-differentiation withmore » large necrotic areas. Based on proliferating cell nuclear antigen (PCNA) staining and expression of cyclins D1, D2, E, and A, vorinostat seems to impair proliferation by down-regulating the expression of these proteins. However, it also induced apoptosis. The mechanism by which vorinostat blocks proliferation and makes tumor cells prone to apoptosis, involved inhibition of mTOR signaling which was accompanied by reduction in cell survival AKT and extracellular-signal regulated kinase (ERK) signaling pathways. Our data provide a novel mechanism-based therapeutic intervention for cutaneous squamous cell carcinoma (SCC). Vorinostat may be utilized to cure skin neoplasms in organ transplant recipient (OTR). These patients have high morbidity and surgical removal of these lesions which frequently develop in these patients, is difficult. -- Highlights: ► Vorinostat reduces SCC growth in a xenograft murine model. ► Vorinostat dampens proliferation and induces apoptosis in tumor cells. ► Diminution in mTOR, Akt and ERK signaling underlies inhibition in proliferation. ► Vorinostat by inhibiting HDACs inhibits epithelial–mesenchymal transition.« less

  7. Establishment of an ASPL-TFE3 renal cell carcinoma cell line (S-TFE)

    PubMed Central

    Hirobe, Megumi; Masumori, Naoya; Tanaka, Toshiaki; Kitamura, Hiroshi; Tsukamoto, Taiji

    2013-01-01

    Xp11 translocation renal cell carcinoma is a rare disease diagnosed in children and adolescents in the advanced stage with an aggressive clinical course. Various gene fusions including the transcription factor E3 (TFE3) gene located on chromosome X cause the tumor. We established an Xp11 translocation renal cell carcinoma cell line from a renal tumor in a 18-y-old Japanese female and named it “S-TFE.” The cell line and its xenograft demonstrated definite gene fusion including TFE3. They showed strong nuclear staining for TFE3 in immunohistochemistry, TFE3 gene rearrangement in dual-color, break-apart FISH analysis and ASPL-TFE3 type 1 fusion transcripts detected by RT-PCR and direct DNA sequencing. Although many renal cell carcinoma cell lines have been established and investigated, only a few cell lines are recognized as Xp11.2 translocation carcinoma. S-TFE will be useful to examine the characteristics and drug susceptibility of Xp11 translocation renal cell carcinoma. PMID:23760492

  8. Establishment of an ASPL-TFE3 renal cell carcinoma cell line (S-TFE).

    PubMed

    Hirobe, Megumi; Masumori, Naoya; Tanaka, Toshiaki; Kitamura, Hiroshi; Tsukamoto, Taiji

    2013-06-01

    Xp11 translocation renal cell carcinoma is a rare disease diagnosed in children and adolescents in the advanced stage with an aggressive clinical course. Various gene fusions including the transcription factor E3 (TFE3) gene located on chromosome X cause the tumor. We established an Xp11 translocation renal cell carcinoma cell line from a renal tumor in a 18-y-old Japanese female and named it "S-TFE." The cell line and its xenograft demonstrated definite gene fusion including TFE3. They showed strong nuclear staining for TFE3 in immunohistochemistry, TFE3 gene rearrangement in dual-color, break-apart FISH analysis and ASPL-TFE3 type 1 fusion transcripts detected by RT-PCR and direct DNA sequencing. Although many renal cell carcinoma cell lines have been established and investigated, only a few cell lines are recognized as Xp11.2 translocation carcinoma. S-TFE will be useful to examine the characteristics and drug susceptibility of Xp11 translocation renal cell carcinoma.

  9. DNA hypermethylation profiles in squamous cell carcinoma of the vulva.

    PubMed

    Stephen, Josena K; Chen, Kang Mei; Raitanen, Misa; Grénman, Seija; Worsham, Maria J

    2009-01-01

    Gene silencing through promoter hypermethylation is a growing concept in the development of human cancers. In this study, we examined the contribution of aberrant methylation of promoter regions in methylation-prone tumor suppressors to the pathogenesis of vulvar cancer. Thirteen cell lines from 12 patients with squamous cell carcinoma of the vulva were evaluated for aberrant methylation status and gene copy number alterations, concomitantly, using the methylation-specific multiplex ligation-dependent probe amplification assay. Of the 22 tumor suppressor genes examined, aberrant methylation was observed for 9 genes: tumor protein p73 (TP73), fragile histidine triad (FHIT), von Hippel-Lindau (VHL), adenomatosis polyposis coli (APC), estrogen receptor 1 (ESR1), cyclin-dependent kinase inhibitor 2B (CDKN2B), death-associated protein kinase 1 (DAPK1), glutathione S-transferase pi (GSTP1), and immunoglobin superfamily, member 4 (IGSF4). The most frequently methylated genes included TP73 in 9 of 13 cell lines, and IGSF4, DAPK1, and FHIT in 3 of 13 cell lines. Methylation-specific polymerase chain reaction was performed for TP73 and FHIT to confirm aberrant methylation by methylation-specific multiplex ligation-dependent probe amplification. In the context of gene copy number and methylation status, both copies of the TP73 gene were hypermethylated. Loss or decreased mRNA expression of TP73 and IGSF4 by reverse transcription polymerase chain reaction confirmed aberrant methylation. Frequent genetic alterations of loss and gain of gene copy number included gain of GSTP1 and multiple endocrine neoplasia type 1 (MEN1), and loss of malignant fibrous histiocytoma amplified sequence 1 (MFHAS1) and IGSF4 in over 50% of the squamous cell carcinoma of the vulva cell lines. These findings underscore the contribution of both genetic and epigenetic events to the underlying pathogenesis of squamous cell carcinoma of the vulva.

  10. Axillary basal cell carcinoma in patients with Goltz-Gorlin syndrome: report of basal cell carcinoma in both axilla of a woman with basal cell nevus syndrome and literature review.

    PubMed

    Cohen, Philip R

    2014-08-17

    Basal cell carcinoma of the axilla, an area that is not usually exposed to the sun, is rare. Individuals with basal cell nevus syndrome, a disorder associated with a mutation in the patch 1 (PTCH1) gene, develop numerous basal cell carcinomas. To describe a woman with basal cell nevus syndrome who developed a pigmented basal cell carcinoma in each of her axilla and to review the features of axillary basal cell carcinoma patients with Goltz-Gorlin syndrome. Pubmed was used to search the following terms: axillary basal cell carcinoma and basal cell nevus syndrome. The papers and their citations were evaluated. Basal cell nevus syndrome patients with basal cell carcinoma of the axilla were observed in two women; this represents 2.5% (2 of 79) of the patients with axillary basal cell carcinoma. Both women had pigmented tumors that were histologically nonaggressive. The cancers did not recur after curettage or excision. Basal cell carcinoma of the axilla has only been described in 79 individuals; two of the patients were women with pigmented tumors who had basal cell nevus syndrome. Similar to other patients with axillary basal cell carcinoma, the tumors were histologically nonaggressive and did not recur following treatment. Whether PTCH1 gene mutation predisposes basal cell nevus patients to develop axillary basal cell carcinomas remains to be determined.

  11. Phase I/II Study of Postoperative Adjuvant Chemoradiation for Advanced-Stage Cutaneous Squamous Cell Carcinoma of the Head and Neck (cSCCHN)

    ClinicalTrials.gov

    2014-11-17

    Recurrent Skin Cancer; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Squamous Cell Carcinoma of the Skin; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity

  12. Human papillomavirus-mediated carcinogenesis and HPV-associated oral and oropharyngeal squamous cell carcinoma. Part 2: Human papillomavirus associated oral and oropharyngeal squamous cell carcinoma

    PubMed Central

    2010-01-01

    Human papillomavirus (HPV) infection of the mouth and oropharynx can be acquired by a variety of sexual and social forms of transmission. HPV-16 genotype is present in many oral and oropharyngeal squamous cell carcinomata. It has an essential aetiologic role in the development of oropharyngeal squamous cell carcinoma in a subset of subjects who are typically younger, are more engaged with high-risk sexual behaviour, have higher HPV-16 serum antibody titer, use less tobacco and have better survival rates than in subjects with HPV-cytonegative oropharyngeal squamous cell carcinoma. In this subset of subjects the HPV-cytopositive carcinomatous cells have a distinct molecular profile. In contrast to HPV-cytopositive oropharyngeal squamous cell carcinoma, the causal association between HPV-16 and other high-risk HPV genotypes and squamous cell carcinoma of the oral mucosa is weak, and the nature of the association is unclear. It is likely that routine administration of HPV vaccination against high-risk HPV genotypes before the start of sexual activity will bring about a reduction in the incidence of HPV-mediated oral and oropharyngeal squamous cell carcinoma. This article focuses on aspects of HPV infection of the mouth and the oropharynx with emphasis on the link between HPV and squamous cell carcinoma, and on the limitations of the available diagnostic tests in identifying a cause-and-effect relationship of HPV with squamous cell carcinoma of the mouth and oropharynx. PMID:20633288

  13. Carcinocythaemia (carcinoma cell leukaemia) in a dog: an acute leukaemia-like picture due to metastatic carcinoma.

    PubMed

    Amati, M; Miele, F; Avallone, G; Banco, B; Bertazzolo, W

    2012-08-01

    An eight-year-old entire female boxer was presented with a two-week history of anorexia and lethargy and two-day history of unilateral left epistaxis. Clinical findings and laboratory test results suggested disseminated intravascular coagulation. On blood smear evaluation, occasional large epithelioid-like unclassified cells were detected. Occasionally these cells were organised in small clusters. Bone marrow examination revealed a marked infiltration by a malignant population of the same epithelioid-like cells. The dog was euthanased because of the guarded prognosis. Following histology and immunohistochemistry, a widespread undifferentiated carcinoma of unknown primary origin was diagnosed. To the authors' knowledge, this is the first case of carcinoma cell leukaemia reported in a dog. Carcinoma cell leukaemia is a rare oncological condition previously described in humans, characterised by non-haematopoietic neoplastic cells in peripheral blood. © 2012 British Small Animal Veterinary Association.

  14. Proteomic Studies of Cholangiocarcinoma and Hepatocellular Carcinoma Cell Secretomes

    PubMed Central

    Srisomsap, Chantragan; Sawangareetrakul, Phannee; Subhasitanont, Pantipa; Chokchaichamnankit, Daranee; Chiablaem, Khajeelak; Bhudhisawasdi, Vaharabhongsa; Wongkham, Sopit; Svasti, Jisnuson

    2010-01-01

    Cholangiocarcinoma (CCA) and hepatocellular carcinoma (HCC) occur with relatively high incidence in Thailand. The secretome, proteins secreted from cancer cells, are potentially useful as biomarkers of the diseases. Proteomic analysis was performed on the secreted proteins of cholangiocarcinoma (HuCCA-1) and hepatocellular carcinoma (HCC-S102, HepG2, SK-Hep-1, and Alexander) cell lines. The secretomes of the five cancer cell lines were analyzed by SDS-PAGE combined with LC/MS/MS. Sixty-eight proteins were found to be expressed only in HuCCA-1. Examples include neutrophil gelatinase-associated lipocalin (lipocalin 2), laminin 5 beta 3, cathepsin D precursor, desmoplakin, annexin IV variant, and annexin A5. Immunoblotting was used to confirm the presence of lipocalin 2 in conditioned media and cell lysate of 5 cell lines. The results showed that lipocalin 2 was a secreted protein which is expressed only in the conditioned media of the cholangiocarcinoma cell line. Study of lipocalin 2 expression in different types of cancer and normal tissues from cholangiocarcinoma patients showed that lipocalin 2 was expressed only in the cancer tissues. We suggest that lipocalin 2 may be a potential biomarker for cholangiocarcinoma. PMID:20069059

  15. Primary paranasal sinus hyalinizing clear cell carcinoma: a case report.

    PubMed

    AlAli, Batool M; Alyousef, Mohammed J; Kamel, Ahmad Salah; Al Hamad, Mohammad A; Al-Bar, Mohammad H; Algowiez, Roaa M

    2017-09-25

    Hyalinizing clear cell carcinoma (HCCC) is a rare low-grade tumour of salivary glands that was first described as a distinct entity in 1994 by Milchgrub et al. EWSR1-ATF1 fusion was found to be specific for this tumour. The majority of the reported cases of HCCC arise from minor salivary glands within the oral cavity. Primary HCCC of the paranasal sinus is extremely uncommon. To our knowledge, only three cases have been reported in the English literature. Herein, we present a case of HCCC of the posterior ethmoid/maxillary sinus. A 63-year-old lady who presented with a long history of epistaxis. CT scan revealed a destructive mass in the left ethmoid/posterior maxillary sinus extending to the nasal cavity. Surgical excision was done and microscopic evaluation showed a tumour composed mainly of nests of clear epithelial cells separated by fibrocellular and hyalinized septa with extensive bone destruction. The tumour cells expressed CK5/6, EMA and p63 immunohistochemically but were negative for S100 protein, PAX-8, RCC and CK7. Sinonasal renal cell-like adenocarcinomas, myoepithelial carcinoma and metastatic renal cell carcinoma were excluded by radiological and immunohistochemical studies. Fluorescence in situ hybridization analysis revealed an EWSR1 gene rearrangement. Postoperative radiation was administrated and the patient did not show recurrence or distant metastasis 4 months after the surgery. Head and neck region have many tumours that demonstrate clear cell changes on histology. Thus, the differential diagnosis for HCCC is wide. Awareness of this rare entity and the possibility of it is arising in unusual location is necessary. EWSR1-AFT1 fusion, a consistent finding in HCCC, can be used to confirm the diagnosis.

  16. Non-Small Cell Carcinoma of the Lung With Osteoclast-Like Giant Cells.

    PubMed

    Dahm, Hans Helmut

    2017-05-01

    Carcinomas of the lung with benign osteoclast-like giant cells are rare. A literature search showed only 8 previously reported examples. These tumors resemble a giant cell tumor of bone. Many of these tumors, which occur in most epithelium-containing organs, are composed of an undifferentiated, sarcomatoid component that contains benign osteoclast-like giant cells and a conventional carcinoma. In some tumors the epithelial origin may be revealed by immunohistochemistry only; others lack any evidence of an epithelial component. A 59-year-old man had an inoperable tumor in the upper lobe of the left lung. The tumor did not respond to radiation therapy, and chemotherapy resulted in minimal relief of symptoms. Light microscopy of biopsy samples showed benign osteoclast-like giant cells distributed irregularly between proliferations of undifferentiated medium-sized tumor cells. Approximately one third of the undifferentiated tumor cells were cytokeratin AE1/AE3-positive, and a minor alveolar clear cell component of the tumor was cytokeratin 7-positive. The osteoclast-like giant cells were strongly CD68-positive. The clinical and histologic findings supported the diagnosis of a non-small cell carcinoma of the lung with benign osteoclast-like giant cells. The differential diagnosis is composed of giant cell carcinoma, carcinosarcoma, and mesenchymal tumors of the lung.

  17. Introducing Cytology-Based Theranostics in Oral Squamous Cell Carcinoma: A Pilot Program.

    PubMed

    Patrikidou, Anna; Valeri, Rosalia Maria; Kitikidou, Kyriaki; Destouni, Charikleia; Vahtsevanos, Konstantinos

    2016-04-01

    We aimed to evaluate the feasibility and reliability of brush cytology in the biomarker expression profiling of oral squamous cell carcinomas within the concept of theranostics, and to correlate this biomarker profile with patient measurable outcomes. Markers representative of prognostic gene expression changes in oral squamous cell carcinoma was selected. These markers were also selected to involve pathways for which commercially available or investigational agents exist for clinical application. A set of 7 markers were analysed by immunocytochemistry on the archival primary tumour material of 99 oral squamous cell carcinoma patients. We confirmed the feasibility of the technique for the expression profiling of oral squamous cell carcinomas. Furthermore, our results affirm the prognostic significance of the epidermal growth factor receptor (EGFR) family and the angiogenic pathway in oral squamous cell carcinoma, confirming their interest for targeted therapy. Brush cytology appears feasible and applicable for the expression profiling of oral squamous cell carcinoma within the concept of theranostics, according to sample availability.

  18. Trefoil Factor 3 as a Novel Biomarker to Distinguish Between Adenocarcinoma and Squamous Cell Carcinoma

    PubMed Central

    Wang, Xiao-Nan; Wang, Shu-Jing; Pandey, Vijay; Chen, Ping; Li, Qing; Wu, Zheng-Sheng; Wu, Qiang; Lobie, Peter E.

    2015-01-01

    Abstract In carcinoma, such as of the lung, the histological subtype is important to select an appropriate therapeutic strategy for patients. However, carcinomas with poor differentiation cannot always be distinguished on the basis of morphology alone nor on clinical findings. Hence, delineation of poorly differentiated adenocarcinoma and squamous cell carcinoma, the 2 most common epithelial-origin carcinomas, is pivotal for selection of optimum therapy. Herein, we explored the potential utility of trefoil factor 3 (TFF3) as a biomarker for primary lung adenocarcinoma and extrapulmonary adenocarcinomas derived from different organs. We observed that 90.9% of lung adenocarcinomas were TFF3-positive, whereas no expression of TFF3 was observed in squamous cell carcinomas. The subtype of lung carcinoma was confirmed by four established biomarkers, cytokeratin 7 and thyroid transcription factor 1 for adenocarcinoma and P63 and cytokeratin 5/6 for squamous cell carcinoma. Furthermore, expression of TFF3 mRNA was observed by quantitative PCR in all of 11 human lung adenocarcinoma cell lines and highly correlated with markers of the adenocarcinomatous lineage. In contrast, little or no expression of TFF3 was observed in 4 lung squamous cell carcinoma cell lines. By use of forced expression, or siRNA-mediated depletion of TFF3, we determined that TFF3 appeared to maintain rather than promote glandular differentiation of lung carcinoma cells. In addition, TFF3 expression was also determined in adenocarcinomas from colorectum, stomach, cervix, esophagus, and larynx. Among all these extrapulmonary carcinomas, 93.7% of adenocarcinomas exhibited TFF3 positivity, whereas only 2.9% of squamous cell carcinomas were TFF3-positive. Totally, 92.9% of both pulmonary and extrapulmonary adenocarcinomas exhibited TFF3 positivity, whereas only 1.5% of squamous cell carcinomas were TFF3-positive. In conclusion, TFF3 is preferentially expressed in adenocarcinoma and may function as an

  19. Ficlatuzumab With or Without Cetuximab in Treating Patients With Cetuximab-Resistant, Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

    ClinicalTrials.gov

    2018-02-02

    Head and Neck Basaloid Carcinoma; Recurrent Head and Neck Squamous Cell Carcinoma; Recurrent Oropharyngeal Squamous Cell Carcinoma; Squamous Cell Carcinoma of Unknown Primary Origin; Stage IV Lip and Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IV Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v7; Stage IV Nasopharyngeal Keratinizing Squamous Cell Carcinoma AJCC v7; Stage IV Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Lip and Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVA Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v7; Stage IVA Nasopharyngeal Keratinizing Squamous Cell Carcinoma AJCC v7; Stage IVA Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Lip and Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVB Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v7; Stage IVB Nasopharyngeal Keratinizing Squamous Cell Carcinoma AJCC v7; Stage IVB Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVC Lip and Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVC Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v7; Stage IVC Nasopharyngeal Keratinizing Squamous Cell Carcinoma AJCC v7; Stage IVC Oropharyngeal Squamous Cell Carcinoma AJCC v7; Head and Neck Cancer; Oropharyngeal Cancer; HNSCC

  20. The genetic landscape of endometrial clear cell carcinomas.

    PubMed

    DeLair, Deborah F; Burke, Kathleen A; Selenica, Pier; Lim, Raymond S; Scott, Sasinya N; Middha, Sumit; Mohanty, Abhinita S; Cheng, Donavan T; Berger, Michael F; Soslow, Robert A; Weigelt, Britta

    2017-10-01

    Clear cell carcinoma of the endometrium is a rare type of endometrial cancer that is generally associated with an aggressive clinical behaviour. Here, we sought to define the repertoire of somatic genetic alterations in endometrial clear cell carcinomas (ECCs), and whether ECCs could be classified into the molecular subtypes described for endometrial endometrioid and serous carcinomas. We performed a rigorous histopathological review, immunohistochemical analysis and massively parallel sequencing targeting 300 cancer-related genes of 32 pure ECCs. Eleven (34%), seven (22%) and six (19%) ECCs showed abnormal expression patterns for p53, ARID1A, and at least one DNA mismatch repair (MMR) protein, respectively. Targeted sequencing data were obtained from 30 of the 32 ECCs included in this study, and these revealed that two ECCs (7%) were ultramutated and harboured mutations affecting the exonuclease domain of POLE. In POLE wild-type ECCs, TP53 (46%), PIK3CA (36%), PPP2R1A (36%), FBXW7 (25%), ARID1A (21%), PIK3R1 (18%) and SPOP (18%) were the genes most commonly affected by mutations; 18% and 11% harboured CCNE1 and ERBB2 amplifications, respectively, and 11% showed DAXX homozygous deletions. ECCs less frequently harboured mutations affecting CTNNB1 and PTEN but more frequently harboured PPP2R1A and TP53 mutations than non-POLE endometrioid carcinomas from The Cancer Genome Atlas (TCGA). Compared to endometrial serous carcinomas (TCGA), ECCs less frequently harboured TP53 mutations. When a surrogate model for the molecular-based TCGA classification was used, all molecular subtypes previously identified in endometrial endometrioid and serous carcinomas were present in the ECCs studied, including POLE, MMR-deficient, copy-number high (serous-like)/p53 abnormal, and copy-number low (endometrioid)/p53 wild-type, which were significantly associated with disease-free survival in univariate analysis. These findings demonstrate that ECCs constitute a histologically and

  1. Breast Cancer with Synchronous Renal Cell Carcinoma: A Rare Presentation.

    PubMed

    Arjunan, Ravi; Kumar, Durgesh; Kumar, K V Veerendra; Premlatha, C S

    2016-10-01

    Primary cancer arising from multiple organs is a well known fact. Synchronous tumours have been most commonly associated with kidney cancer. Bladder, prostate, colorectal and lung cancer are the most common synchronous primaries with Renal Cell Carcinoma (RCC) identified till date. We found metachronous tumours of breast with RCC in literature search which included both metastatic tumours as well second primaries. Overall, 25 cases of metastatic breast tumours and eight cases of second primary in previously treated RCC have been reported in the literature. Here, we are reporting a case of synchronous presentation of carcinoma breast with RCC which is very rare because most of the multiple malignancies reported in the literature are metastatic tumours or metachronous breast malignancy with RCC.

  2. Breast Cancer with Synchronous Renal Cell Carcinoma: A Rare Presentation

    PubMed Central

    Arjunan, Ravi; Kumar, K V Veerendra; Premlatha, C S

    2016-01-01

    Primary cancer arising from multiple organs is a well known fact. Synchronous tumours have been most commonly associated with kidney cancer. Bladder, prostate, colorectal and lung cancer are the most common synchronous primaries with Renal Cell Carcinoma (RCC) identified till date. We found metachronous tumours of breast with RCC in literature search which included both metastatic tumours as well second primaries. Overall, 25 cases of metastatic breast tumours and eight cases of second primary in previously treated RCC have been reported in the literature. Here, we are reporting a case of synchronous presentation of carcinoma breast with RCC which is very rare because most of the multiple malignancies reported in the literature are metastatic tumours or metachronous breast malignancy with RCC. PMID:27891445

  3. Basal cell carcinoma of the nipple - an unusual location in a male patient.

    PubMed

    Avci, Oktay; Pabuççuoğlu, Uğur; Koçdor, M Ali; Unlü, Mehtat; Akin, Ciler; Soyal, Cüneyt; Canda, Tülay

    2008-02-01

    Although basal cell carcinoma is extremely common, it only rarely occurs on the nipple. Men are affected more often than women. Basal cell carcinoma of the nipple-areola complex may be more aggressive as metastases to regional lymph nodes have been reported. We report a basal cell carcinoma of the nipple with features of a fibroepithelioma of Pinkus in a man and review the literature.

  4. Nucleolar Organizer Regions in Oral Squamous Cell Carcinoma

    PubMed Central

    Moradzadeh Khiavi, Monir; Vosoughhosseini, Sepideh; Halimi, Monire; Mahmoudi, Seyyed Mostafa; Yarahmadi, Asghar

    2012-01-01

    Background and aims Several diagnostic methods are being employed to detect benign and malignant lesions, one of which is silver nitrate staining for organizer regions. The number of nucleolar organizing regions (NORs) can be used to show the degree of cell activity or metabolism in pathologic lesions. This study was designed to evaluate NORs as determi-nants of precancerous and squamous cell carcinoma. Materials and methods A silver colloid technique was applied on paraffin sections of 40 cases of oral squamous cell carcinoma and 25 cases of precancerous lesions; 15 specimens of normal epithelium were selected for the control group. After staining with silver nitrate, argyrophilic nucleolar organizer regions (AgNORs) were counted in 100 epithelial cells in three groups with the use of an oil immersion and ×1000 objective lens. One-way ANOVA and a post hoc Tukey test were used for statistical analysis. Results The mean numbers and standard deviations of AgNORs were 1.58 ± 0.76 in normal epithelium, 2.1 ± 1.05 in pre-cancerous lesions and 2.43 ±1.33 in squamous cell carcinoma (SCC). There were statistically significant differences in Ag-NORs numbers between the groups (P<0.001) and significant differences in precancerous lesions between dysplastic and non-dysplastic epithelia (P<0.001). The mean AgNORs count per nucleus increased from healthy epithelium to precancer-ous lesion to SCC. Conclusion This study suggests that the silver staining technique for the detection of NORs (AgNOR) can be used to distinguish precancerous lesions and benign and malignant lesions. PMID:22991629

  5. Chromophobe Renal Cell Carcinoma is the Most Common Nonclear Renal Cell Carcinoma in Young Women: Results from the SEER Database.

    PubMed

    Daugherty, Michael; Blakely, Stephen; Shapiro, Oleg; Vourganti, Srinivas; Mollapour, Mehdi; Bratslavsky, Gennady

    2016-04-01

    The renal cell cancer incidence is relatively low in younger patients, encompassing 3% to 7% of all renal cell cancers. While young patients may have renal tumors due to hereditary syndromes, in some of them sporadic renal cancers develop without any family history or known genetic mutations. Our recent observations from clinical practice have led us to hypothesize that there is a difference in histological distribution in younger patients compared to the older cohort. We queried the SEER (Surveillance, Epidemiology and End Results) 18-registry database for all patients 20 years old or older who were surgically treated for renal cell carcinoma between 2001 and 2008. Patients with unknown race, grade, stage or histology and those with multiple tumors were excluded from study. Four cohorts were created by dividing patients by gender, including 1,202 females and 1,715 males younger than 40 years old, and 18,353 females and 30,891 males 40 years old or older. Chi-square analysis was used to compare histological distributions between the cohorts. While clear cell carcinoma was still the most common renal cell cancer subtype across all genders and ages, chromophobe renal cell cancer was the most predominant type of nonclear renal cell cancer histology in young females, representing 62.3% of all nonclear cell renal cell cancers (p <0.0001). In all other groups papillary renal cell cancer remained the most common type of nonclear renal cell cancer. It is possible that hormonal factors or specific pathway dysregulations predispose chromophobe renal cell cancer to develop in younger women. We hope that this work provides some new observations that could lead to further studies of gender and histology specific renal tumorigenesis. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  6. TMPRSS2-ERG gene fusion in small cell carcinoma of the prostate.

    PubMed

    Guo, Charles C; Dancer, Jane Y; Wang, Yan; Aparicio, Ana; Navone, Nora M; Troncoso, Patricia; Czerniak, Bogdan A

    2011-01-01

    Recent studies have shown that most prostate cancers carry the TMPRSS2-ERG gene fusion. Here we evaluated the TMPRSS2-ERG gene fusion in small cell carcinoma of the prostate (n = 12) in comparison with small cell carcinoma of the urinary bladder (n = 12) and lung (n = 11). Fluorescence in situ hybridization demonstrated rearrangement of the ERG gene in 8 cases of prostatic small cell carcinoma (67%), and the rearrangement was associated with deletion of the 5' ERG gene in 7 cases, but rearrangement of the ERG gene was not present in any small cell carcinoma of the urinary bladder or lung. Next we evaluated the TMPRSS2-ERG gene fusion in nude mouse xenografts that were derived from 2 prostatic small cell carcinomas carrying the TMPRSS2-ERG gene fusion. Two transcripts encoded by the TMPRSS2-ERG gene fusion were detected by reverse transcriptase polymerase chain reaction, and DNA sequencing demonstrated that the 2 transcripts were composed of fusions of exon 1 of the TMPRSS2 gene to exon 4 or 5 of the ERG gene. Our study demonstrates the specific presence of TMPRSS2-ERG gene fusion in prostatic small cell carcinoma, which may be helpful in distinguishing small cell carcinoma of prostatic origin from nonprostatic origins. The high prevalence of the TMPRSS2-ERG gene fusion in prostatic small cell carcinoma as well as adenocarcinoma implies that small cell carcinoma may share a common pathogenic pathway with adenocarcinoma in the prostate. Copyright © 2011 Elsevier Inc. All rights reserved.

  7. AgNORs in hyperplasia, papilloma and oral squamous cell carcinoma.

    PubMed

    Fonseca, L M; do Carmo, M A

    2000-01-01

    Ten inflammatory fibrous hyperplasias, ten papillomas, and nineteen oral squamous cell carcinomas were analyzed by the AgNOR technique to determine if different disturbances of oral epithelia presented different AgNOR counts. The papilloma group showed higher mean AgNOR counts (3.15 +/- 0.58) than the hyperplasia group (1.98 +/- 0.24) and smaller than the well-differentiated oral squamous cell carcinoma group (6.56 +/- 1.25) and poorly differentiated oral squamous cell carcinoma group (7.07 +/- 1.60). The differences among the groups of lesions were statistically significant (P < 0.05) except between the well differentiated oral squamous cell carcinoma group and the poorly differentiated oral squamous cell carcinoma group. Our findings suggest that the cellular proliferation ratio in papillomas is greater than hyperplasias and smaller than carcinomas.

  8. Association of cystic neck metastases and human papillomavirus-positive oropharyngeal squamous cell carcinoma.

    PubMed

    McHugh, Jonathan B

    2009-11-01

    Human papillomavirus is an established cause of oropharyngeal squamous cell carcinoma. Similar to cervical cancer, these cancers are usually caused by high-risk human papillomavirus types 16 and 18 and are associated with high-risk sexual behaviors. Human papillomavirus-associated oropharyngeal squamous cell carcinoma typically affects the palatine and lingual tonsils and frequently results in cystic neck metastases. The histopathology of this subset of head and neck squamous cell carcinoma is unique and typically characterized by poorly differentiated, nonkeratinizing morphology with a basaloid appearance. These tumors occur in younger patients and are more often seen in nonsmokers compared with conventional oral cavity and oropharyngeal squamous cell carcinomas. The incidence of human papillomavirus-associated squamous cell carcinoma is increasing. Recognition of this unique clinicopathologic subset of head and neck carcinoma is important because these patients typically respond more favorably to organ-sparing treatment modalities and have an improved prognosis.

  9. Ovarian malignant mixed germ cell tumor with clear cell carcinoma in a postmenopausal woman.

    PubMed

    Yu, Xiu-Jie; Zhang, Lin; Liu, Zai-Ping; Shi, Yi-Quan; Liu, Yi-Xin

    2014-01-01

    Malignant germ cell tumors of the ovary are very rare and account for about 2-5% of all ovarian tumors of germ origin. Most patients are adolescent and young women, approximately two-thirds of them are under 20 years of age, occasionally in postmenopausal women. But clear cell carcinoma usually occurs in older patients (median age: 57-year old), and closely related with endometriosis. Here we report a case of a 55-year old woman with right ovarian mass that discovered by B ultrasonic. Her serum levels of human chorionic gonadotropin (hCG) and α-fetoprotein (AFP) were elevated. Pathological examination revealed the tumor to be a mixed germ cell tumor (yolk sac tumor, embryonal carcinoma and mature teratoma) with clear cell carcinoma in a background of endometriosis. Immunohistochemical staining showed SALL4 and PLAP were positive in germ cell tumor area, hCG, CD30 and OCT4 were positive in epithelial-like cells and giant synctiotrophoblastic cells, AFP, AAT, CD117 and Glyp3 were positive in yolk sac component, EMA and CK7 were positive in clear cell carcinoma, CD10 was positive in endometrial cells of endometriotic area. She was treated with surgery followed by seven courses of chemotherapy. She is well and serum levels of hCG and AFP have been decreased to normal levels.

  10. Single-cell genetic analysis validates cytopathological identification of circulating cancer cells in patients with clear cell renal cell carcinoma.

    PubMed

    Broncy, Lucile; Njima, Basma Ben; Méjean, Arnaud; Béroud, Christophe; Romdhane, Khaled Ben; Ilie, Marius; Hofman, Veronique; Muret, Jane; Hofman, Paul; Bouhamed, Habiba Chaabouni; Paterlini-Bréchot, And Patrizia

    2018-04-13

    Circulating Rare Cells (CRC) are non-haematological cells circulating in blood. They include Circulating Cancer Cells (CCC) and cells with uncertain malignant features (CRC-UMF) according to cytomorphology. Clear cell renal cell carcinomas frequently bear a mutated Von Hippel-Lindau (VHL) gene. To match blind genetic analysis of CRC and tumor samples with CRC cytopathological diagnosis. 29/30 patients harboured CRC (20 harboured CCC, 29 CRC-UMF) and 25/29 patients carried VHL mutations in their tumour. 205 single CRC (64 CCC, 141 CRC-UMF) provided genetic data. 57/57 CCC and 104/125 CRC-UMF from the 25 patients with VHL-mutated tumor carried the same VHL mutation detected in the tumor. Seven CCC and 16 CRC-UMF did not carry VHL mutations but were found in patients with wild-type VHL tumor tissue. All the CCC and 83,2% (104/125) of the CRC-UMF were found to carry the same VHL mutation identified in the corresponding tumorous tissue, validating cytopathological identification of CCC in patients with clear cell renal cell carcinoma. The blood of 30 patients with clear cell renal cell carcinoma was treated by ISET ® for CRC isolation, cytopathology and single-cell VHL mutations analysis, performed blindly and compared to VHL mutations of corresponding tumor tissues and leukocytes.

  11. Merkel Cell Carcinoma of the Buccal Mucosa and Lower Lip.

    PubMed

    Islam, Mohammed N; Chehal, Hardeep; Smith, Molly Housley; Islam, Sarah; Bhattacharyya, Indraneel

    2018-06-01

    Merkel cell carcinoma (MCC) is an uncommon relatively aggressive neuroendocrine dermal neoplasm first described in 1972 as a tumor of the sun exposed skin. Although most MCC affect the skin of the head and neck, rare primarily oral mucosal cases have been documented. Merkel cells are nondendritic neuroendocrine cells that are found not only in the skin but also the oral mucosa and give rise to MCC. Neuroendocrine cells may be found as aggregates in organs or as diffuse or isolated cells within organs and their epithelial lining. They contain peptide hormones and biogenic amines and occur in two forms: dendritic, which are not associated with nerve fibers and non-dendritic, which are associated with nerve fibers. Merkel cells as well as MCC express simple epithelium-type Cytokeratins (8, 18, 19, 20), neurosecretory substances; chromogranin A, synaptophysin, neuron-specific enolase (NSE), adhesion molecules, and villin (intermediate filament). Though weakly, they also express neural markers such as S-100 protein. Cytokeratin 20, and Cluster of differentiation 56, are the two key diagnostic markers for Merkel cells and MCC. Etiology includes UV radiation, the recently described Merkel cell polyomavirus, and long term systemic immunosuppression. The cutaneous and mucosal variants of MCC are considered aggressive tumors with a high risk for local recurrence and metastasis and should be considered in the differential diagnosis of head and neck mucosal lesions. We present two cases of primary Merkel cell carcinoma, one on the buccal mucosa and the other on the lower lip, and discuss the salient histologic, immunohistochemical and clinical features.

  12. 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.

  13. Integrin-β4 identifies cancer stem cell-enriched populations of partially mesenchymal carcinoma cells

    PubMed Central

    Bierie, Brian; Pierce, Sarah E.; Kroeger, Cornelia; Stover, Daniel G.; Pattabiraman, Diwakar R.; Thiru, Prathapan; Liu Donaher, Joana; Reinhardt, Ferenc; Chaffer, Christine L.; Keckesova, Zuzana; Weinberg, Robert A.

    2017-01-01

    Neoplastic cells within individual carcinomas often exhibit considerable phenotypic heterogeneity in their epithelial versus mesenchymal-like cell states. Because carcinoma cells with mesenchymal features are often more resistant to therapy and may serve as a source of relapse, we sought to determine whether such cells could be further stratified into functionally distinct subtypes. Indeed, we find that a basal epithelial marker, integrin-β4 (ITGB4), can be used to enable stratification of mesenchymal-like triple-negative breast cancer (TNBC) cells that differ from one another in their relative tumorigenic abilities. Notably, we demonstrate that ITGB4+ cancer stem cell (CSC)-enriched mesenchymal cells reside in an intermediate epithelial/mesenchymal phenotypic state. Among patients with TNBC who received chemotherapy, elevated ITGB4 expression was associated with a worse 5-year probability of relapse-free survival. Mechanistically, we find that the ZEB1 (zinc finger E-box binding homeobox 1) transcription factor activity in highly mesenchymal SUM159 TNBC cells can repress expression of the epithelial transcription factor TAp63α (tumor protein 63 isoform 1), a protein that promotes ITGB4 expression. In addition, we demonstrate that ZEB1 and ITGB4 are important in modulating the histopathological phenotypes of tumors derived from mesenchymal TNBC cells. Hence, mesenchymal carcinoma cell populations are internally heterogeneous, and ITGB4 is a mechanistically driven prognostic biomarker that can be used to identify the more aggressive subtypes of mesenchymal carcinoma cells in TNBC. The ability to rapidly isolate and mechanistically interrogate the CSC-enriched, partially mesenchymal carcinoma cells should further enable identification of novel therapeutic opportunities to improve the prognosis for high-risk patients with TNBC. PMID:28270621

  14. Evaluating hepatocellular carcinoma cell lines for tumour samples using within-sample relative expression orderings of genes.

    PubMed

    Ao, Lu; Guo, You; Song, Xuekun; Guan, Qingzhou; Zheng, Weicheng; Zhang, Jiahui; Huang, Haiyan; Zou, Yi; Guo, Zheng; Wang, Xianlong

    2017-11-01

    Concerns are raised about the representativeness of cell lines for tumours due to the culture environment and misidentification. Liver is a major metastatic destination of many cancers, which might further confuse the origin of hepatocellular carcinoma cell lines. Therefore, it is of crucial importance to understand how well they can represent hepatocellular carcinoma. The HCC-specific gene pairs with highly stable relative expression orderings in more than 99% of hepatocellular carcinoma but with reversed relative expression orderings in at least 99% of one of the six types of cancer, colorectal carcinoma, breast carcinoma, non-small-cell lung cancer, gastric carcinoma, pancreatic carcinoma and ovarian carcinoma, were identified. With the simple majority rule, the HCC-specific relative expression orderings from comparisons with colorectal carcinoma and breast carcinoma could exactly discriminate primary hepatocellular carcinoma samples from both primary colorectal carcinoma and breast carcinoma samples. Especially, they correctly classified more than 90% of liver metastatic samples from colorectal carcinoma and breast carcinoma to their original tumours. Finally, using these HCC-specific relative expression orderings from comparisons with six cancer types, we identified eight of 24 hepatocellular carcinoma cell lines in the Cancer Cell Line Encyclopedia (Huh-7, Huh-1, HepG2, Hep3B, JHH-5, JHH-7, C3A and Alexander cells) that are highly representative of hepatocellular carcinoma. Evaluated with a REOs-based prognostic signature for hepatocellular carcinoma, all these eight cell lines showed the same metastatic properties of the high-risk metastatic hepatocellular carcinoma tissues. Caution should be taken for using hepatocellular carcinoma cell lines. Our results should be helpful to select proper hepatocellular carcinoma cell lines for biological experiments. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. MULTIHORMONAL ISLET CELL CARCINOMAS IN THREE KOMODO DRAGONS (VARANUS KOMODOENSIS).

    PubMed

    Eustace, Ronan; Garner, Michael M; Cook, Kimberly; Miller, Christine; Kiupel, Matti

    2017-03-01

      Multihormonal pancreatic islet cell carcinomas were found in one female and two male captive geriatric Komodo dragons (Varanus komodoensis). Gross changes in the pancreas were visible in two of the cases. Clinical signs noted in the Komodo dragons were lethargy, weakness, and anorexia. Histologically, the tumors were comprised of nests and cords of well-differentiated neoplastic islet cells with scant amounts of eosinophilic cytoplasm and round, euchromatic nuclei, with rare mitoses. Infiltration by the islet cell tumor into the surrounding acinar tissue was observed in all cases, but no metastatic foci were seen. Multihormone expression was observed in all tumors, which labeled strongly positive for glucagon and somatostatin and focally positive for polypeptide. Pancreatic islet cell neoplasms should be considered in the differential diagnosis for geriatric Komodo dragons presenting with weakness, lethargy, and poor appetite.

  16. Poly ADP-ribose polymerase-1 as a potential therapeutic target in Merkel cell carcinoma.

    PubMed

    Ferrarotto, Renata; Cardnell, Robert; Su, Shirley; Diao, Lixia; Eterovic, A Karina; Prieto, Victor; Morrisson, William H; Wang, Jing; Kies, Merrill S; Glisson, Bonnie S; Byers, Lauren Averett; Bell, Diana

    2018-03-23

    Patients with metastatic Merkel cell carcinoma are treated similarly to small cell lung cancer (SCLC). Poly ADP-ribose polymerase-1 (PARP1) is overexpressed in SCLC and response to PARP inhibitors have been reported in patients with SCLC. Our study explores PARP as a therapeutic target in Merkel cell carcinoma. We evaluated PARP1 expression and Merkel cell polyomavirus (MCPyV) in 19 patients with Merkel cell carcinoma. Target exome-sequencing was performed in 14 samples. Sensitivity to olaparib was tested in 4 Merkel cell carcinoma cell lines. Most Merkel cell carcinomas (74%) express PARP1 at high levels. Mutations in DNA-damage repair genes were identified in 9 samples (64%), occurred exclusively in head neck primaries, and correlated with TP53/RB1 mutations. The TP53/RB1 mutations were more frequent in MCPyV-negative tumors. Sensitivity to olaparib was seen in the Merkel cell carcinoma line with highest PARP1 expression. Based on PARP1 overexpression, DNA-damage repair gene mutations, platinum sensitivity, and activity of olaparib in a Merkel cell carcinoma line, clinical trials with PARP inhibitors are warranted in Merkel cell carcinoma. © 2018 Wiley Periodicals, Inc.

  17. Surface topography and ultrastructural changes of mucinous carcinoma breast cells.

    PubMed

    Voloudakis, G E; Baltatzis, G E; Agnantis, N J; Arnogianaki, N; Misitzis, J; Voloudakis-Baltatzis, I

    2007-01-01

    Mucinous carcinoma of the breast (MCB) is histologically classified into 2 groups: (1) pure MCB and (2) mixed MCB. Pure MCB carries a better diagnosis than mixed MCB. This research relates to the cell surface topography and ultrastructure of the cells in the above cases and aims to find the differences between them, by means of two methods: scanning electron microscopy (SEM) and transmission electron microscopy (TEM). For the SEM examination, it was necessary to initially culture the MCB tissues and then proceed with the usual SEM method. In contrast, for the TEM technique, MCB tissues were initially fixed followed by the classic TEM method. The authors found the topography of pure MCB cases to be without nodes. The cell membrane was smooth, with numerous pores and small ruffles that covered the entire cell. The ultrastructural appearance of the same cases was with a normal cell membrane containing abundant collagen fibers. They also had many small vesicles containing mucin as well as secretory droplets. In contrast the mixed MCB had a number of lymph nodes and their cell surface topography showed stronger changes such as microvilli, numerous blebs, ruffles and many long projections. Their ultrastructure showed very long microvilli with large cytoplasmic inclusions and extracellular mucin collections, electron-dense material vacuoles, and many important cytoplasmic organelles. An important fact is that mixed MCB also contains areas of infiltrating ductal carcinoma. These cells of the cytoplasmic organelles are clearly responsible for the synthesis, storage, and secretion of the characteristic mucin of this tumor type. Evidently, this abnormal mucin production and the abundance of secretory granules along with the long projections observed in the topographical structure might be responsible for transferring tumor cells to neighboring organs, thus being responsible for metastatic disease.

  18. Protease-activated receptor 2 modulates proliferation and invasion of oral squamous cell carcinoma cells.

    PubMed

    Al-Eryani, Kamal; Cheng, Jun; Abé, Tatsuya; Maruyama, Satoshi; Yamazaki, Manabu; Babkair, Hamzah; Essa, Ahmed; Saku, Takashi

    2015-07-01

    Based on our previous finding that protease-activated receptor 2 (PAR-2) regulates hemophagocytosis of oral squamous cell carcinoma (SCC) cells, which induces their heme oxygenase 1-dependent keratinization, we have formulated a hypothesis that PAR-2 functions in wider activities of SCC cells. To confirm this hypothesis, we investigated immunohistochemical profiles of PAR-2 in oral SCC tissues and its functional roles in cell proliferation and invasion in SCC cells in culture. The PAR-2 expression modes were determined in 48 surgical tissue specimens of oral SCC. Using oral SCC-derived cell systems, we determined both gene and protein expression levels of PAR-2. SCC cell proliferation and invasive properties were also examined in conditions in which PAR-2 was activated by the synthetic peptide SLIGRL. PAR-2 was immunolocalized in oral SCC and carcinoma in situ cells, especially in those on the periphery of carcinoma cell foci (100% of cases), but not in normal oral epithelia. Its expression at both gene and protein levels was confirmed in 3 oral SCC cell lines including ZK-1. Activation of PAR-2 induced ZK-1 cell proliferation in a dose-dependent manner. PAR-2-activated ZK-1 cells invaded faster than nonactivated ones. The expression of PAR-2 is specific to oral malignancies, and PAR-2 regulates the growth and invasion of oral SCC cells. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Histopathologic risk factors in oral and oropharyngeal squamous cell carcinoma variants: An update with special reference to HPV-related carcinomas

    PubMed Central

    2014-01-01

    Accurate identification of the microscopic risk factors of oral and oropharyngeal (OP) squamous cell carcinomas (SCC) and their morphologic variants is of at most importance, as these generally determine treatment modalities, prognosis and overall patient outcome. The great majority of oral and oropharyngeal squamous cell carcinomas are microscopically described as kerartinizing squamous cell carcinoma (KSCC). They bear certain resemblance to keratinizing stratified squamous epithelium. Tobacco habits and excessive consumption of alcoholic beverages have been considered to be the main etiologic agents in these carcinomas. The tumors occurred in older patients more commonly affected the oral tongue and floor of the mouth with well established morphologic risk factors including tumor grade, pattern of invasion and perineural involvement. Within the last 30 years however, the advent and expanding prevalence of high risk human papillomavirus (HPV) as an important etiologic agent for head and neck squamous cell carcinoma, particularly in the OP, has resulted in a significant change in the established morphologic criteria for risk assessment. The majority of HPV relate carcinomas of the OP are nonkeratinizing squamous cell carcinoma (NKSCC). These tumors are found to be more responsive to treatment with a favorable patient outcome and good prognosis. Consequently, alterations in treatment protocols aimed at de-escalation are currently being evaluated. More recently, other morphologic variants that are HPV positive are reported with increasing frequency in the OP and other head and neck sites. As a result, several clinical and pathologic questions have emerged. Importantly, whether the virus is biologically active in these tumors and involved in their pathogenesis, and second, what are the clinical implications with regard to patient management and outcome in the HPV-related variants. Examples of HPV-related squamous cell carcinoma variants that will be addressed here are

  20. Cisplatin, Intensity-Modulated Radiation Therapy, and Pembrolizumab in Treating Patients With Stage III-IV Head and Neck Squamous Cell Carcinoma

    ClinicalTrials.gov

    2018-05-18

    CDKN2A-p16 Negative; Stage III Hypopharyngeal Squamous Cell Carcinoma AJCC v7; Stage III Laryngeal Squamous Cell Carcinoma AJCC v6 and v7; Stage III Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage III Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Hypopharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Laryngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVA Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Hypopharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Laryngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVB Oropharyngeal Squamous Cell Carcinoma AJCC v7

  1. Protein arginine N-methyltransferase 1 promotes the proliferation and metastasis of hepatocellular carcinoma cells.

    PubMed

    Gou, Qing; He, ShuJiao; Zhou, ZeJian

    2017-02-01

    Hepatocellular carcinoma is the most common subtype of liver cancer. Protein arginine N-methyltransferase 1 was shown to be upregulated in various cancers. However, the role of protein arginine N-methyltransferase 1 in hepatocellular carcinoma progression remains incompletely understood. We investigated the clinical and functional significance of protein arginine N-methyltransferase 1 in a series of clinical hepatocellular carcinoma samples and a panel of hepatocellular carcinoma cell lines. We performed suppression analysis of protein arginine N-methyltransferase 1 using small interfering RNA to determine the biological roles of protein arginine N-methyltransferase 1 in hepatocellular carcinoma. In addition, the expression of epithelial-mesenchymal transition indicators was verified by western blotting in hepatocellular carcinoma cell lines after small interfering RNA treatment. Protein arginine N-methyltransferase 1 expression was found to be significantly upregulated in hepatocellular carcinoma cell lines and clinical tissues. Moreover, downregulation of protein arginine N-methyltransferase 1 in hepatocellular carcinoma cells by small interfering RNA could inhibit cell proliferation, migration, and invasion in vitro. These results indicate that protein arginine N-methyltransferase 1 may contribute to hepatocellular carcinoma progression and serves as a promising target for the treatment of hepatocellular carcinoma patients.

  2. BHD Tumor Cell Line and Renal Cell Carcinoma Line | NCI Technology Transfer Center | TTC

    Cancer.gov

    Scientists at the National Cancer Institute  have developed a novel renal cell carcinoma (RCC) cell line designated UOK257, which was derived from the surgical kidney tissue of a patient with hereditary Birt-Hogg-Dube''''(BHD) syndrome and companion cell line UOK257-2 in which FLCN expression has been restored by lentivirus infection. The NCI Urologic Oncology Branch seeks parties interested in licensing or collaborative research to co-develop, evaluate, or commercialize kidney cancer tumor cell lines.

  3. Role of Neurokinin 3 Receptor Signaling in Oral Squamous Cell Carcinoma.

    PubMed

    Obata, Kyoichi; Shimo, Tsuyoshi; Okui, Tatsuo; Matsumoto, Kenichi; Takada, Hiroyuki; Takabatake, Kiyofumi; Kunisada, Yuki; Ibaragi, Soichiro; Yoshioka, Norie; Kishimoto, Koji; Nagatsuka, Hitoshi; Sasaki, Akira

    2017-11-01

    The neurokinin 3 receptor (NK-3R) is differentially expressed in the central nervous system including cases of human oral squamous cell carcinoma. However, the role of NK-3R signaling in oral squamous cell carcinoma is not well known. NK-3R expression in surgically resected oral squamous cell carcinoma was examined immunohistochemically and the strength of the expression was quantified. We evaluated the function of NK-3R signaling using NK-3R antagonist in human oral squamous cell carcinoma bone invasion mouse model. NK-3R was significantly expressed in tumor cells that had invaded the bone matrix compared to the oral side tumor cells. SB222200, a selective antagonist of NK-3R, significantly suppressed the radiographic osteolytic lesion and tumorigenesis. NK-3R signaling is a potential target for the treatment of oral squamous cell carcinoma in cases of bone destruction. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  4. Hemidesmosomal linker proteins regulate cell motility, invasion and tumorigenicity in oral squamous cell carcinoma derived cells.

    PubMed

    Chaudhari, Pratik Rajeev; Charles, Silvania Emlit; D'Souza, Zinia Charlotte; Vaidya, Milind Murlidhar

    2017-11-15

    BPAG1e and Plectin are hemidesmosomal linker proteins which anchor intermediate filament proteins to the cell surface through β4 integrin. Recent reports indicate that these proteins play a role in various cellular processes apart from their known anchoring function. However, the available literature is inconsistent. Further, the previous study from our laboratory suggested that Keratin8/18 pair promotes cell motility and tumor progression by deregulating β4 integrin signaling in oral squamous cell carcinoma (OSCC) derived cells. Based on these findings, we hypothesized that linker proteins may have a role in neoplastic progression of OSCC. Downregulation of hemidesmosomal linker proteins in OSCC derived cells resulted in reduced cell migration accompanied by alterations in actin organization. Further, decreased MMP9 activity led to reduced cell invasion in linker proteins knockdown cells. Moreover, loss of these proteins resulted in reduced tumorigenic potential. SWATH analysis demonstrated upregulation of N-Myc downstream regulated gene 1 (NDRG1) in linker proteins downregulated cells as compared to vector control cells. Further, the defects in phenotype upon linker proteins ablation were rescued upon loss of NDRG1 in linker proteins knockdown background. These data together indicate that hemidesmosomal linker proteins regulate cell motility, invasion and tumorigenicity possibly through NDRG1 in OSCC derived cells. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Collision of Ductal Carcinoma In Situ of Anogenital Mammary-like Glands and Vulvar Sarcomatoid Squamous Cell Carcinoma.

    PubMed

    Tran, Tien A N; Deavers, Michael T; Carlson, J Andrew; Malpica, Anais

    2015-09-01

    A spectrum of invasive adenocarcinomas presumably arising from the anogenital mammary-like glands of the vulva has been reported. Even rarer are the cases of pure ductal carcinoma in situ that originated from these unique glandular structures. Herein, we report an 81-yr-old woman presented with an invasive well-differentiated squamous cell carcinoma of the vulva. Unexpectedly, the underlying dermis demonstrated a cystically dilated structure that displayed a layer of malignant squamous cells in the periphery, and a second centrally located population of neoplastic cells exhibiting glandular differentiation. In addition, a spindle and pleomorphic malignant cell population consistent with a sarcomatoid carcinoma was identified around the cystic structure. Scattered benign anogenital mammary-like glands were present in the adjacent dermis. The histologic and immunohistochemical findings were consistent with those of vulvar squamous cell carcinoma that has undergone sarcomatoid transformation after spreading in a pagetoid fashion into an underlying focus of ductal carcinoma in situ of anogenital mammary-like gland origin.

  6. Characterization of a Merkel Cell Polyomavirus-Positive Merkel Cell Carcinoma Cell Line CVG-1.

    PubMed

    Velásquez, Celestino; Amako, Yutaka; Harold, Alexis; Toptan, Tuna; Chang, Yuan; Shuda, Masahiro

    2018-01-01

    Merkel cell polyomavirus (MCV) plays a causal role in ∼80% of Merkel cell carcinomas (MCC). MCV is clonally integrated into the MCC tumor genome, which results in persistent expression of large T (LT) and small T (sT) antigen oncoproteins encoded by the early locus. In MCV-positive MCC tumors, LT is truncated by premature stop codons or deletions that lead to loss of the C-terminal origin binding (OBD) and helicase domains important for replication. The N-terminal Rb binding domain remains intact. MCV-positive cell lines derived from MCC explants have been valuable tools to study the molecular mechanism of MCV-induced Merkel cell carcinogenesis. Although all cell lines have integrated MCV and express truncated LT antigens, the molecular sizes of the LT proteins differ between cell lines. The copy number of integrated viral genome also varies across cell lines, leading to significantly different levels of viral protein expression. Nevertheless, these cell lines share phenotypic similarities in cell morphology, growth characteristics, and neuroendocrine marker expression. Several low-passage MCV-positive MCC cell lines have been established since the identification of MCV. We describe a new MCV-positive MCV cell line, CVG-1, with features distinct from previously reported cell lines. CVG-1 tumor cells grow in more discohesive clusters in loose round cell suspension, and individual cells show dramatic size heterogeneity. It is the first cell line to encode an MCV sT polymorphism resulting in a unique leucine (L) to proline (P) substitution mutation at amino acid 144. CVG-1 possesses a LT truncation pattern near identical to that of MKL-1 cells differing by the last two C-terminal amino acids and also shows an LT protein expression level similar to MKL-1. Viral T antigen knockdown reveals that, like other MCV-positive MCC cell lines, CVG-1 requires T antigen expression for cell proliferation.

  7. Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma.

    PubMed

    Choueiri, Toni K; Escudier, Bernard; Powles, Thomas; Mainwaring, Paul N; Rini, Brian I; Donskov, Frede; Hammers, Hans; Hutson, Thomas E; Lee, Jae-Lyun; Peltola, Katriina; Roth, Bruce J; Bjarnason, Georg A; Géczi, Lajos; Keam, Bhumsuk; Maroto, Pablo; Heng, Daniel Y C; Schmidinger, Manuela; Kantoff, Philip W; Borgman-Hagey, Anne; Hessel, Colin; Scheffold, Christian; Schwab, Gisela M; Tannir, Nizar M; Motzer, Robert J

    2015-11-05

    Cabozantinib is an oral, small-molecule tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor (VEGFR) as well as MET and AXL, each of which has been implicated in the pathobiology of metastatic renal-cell carcinoma or in the development of resistance to antiangiogenic drugs. This randomized, open-label, phase 3 trial evaluated the efficacy of cabozantinib, as compared with everolimus, in patients with renal-cell carcinoma that had progressed after VEGFR-targeted therapy. We randomly assigned 658 patients to receive cabozantinib at a dose of 60 mg daily or everolimus at a dose of 10 mg daily. The primary end point was progression-free survival. Secondary efficacy end points were overall survival and objective response rate. Median progression-free survival was 7.4 months with cabozantinib and 3.8 months with everolimus. The rate of progression or death was 42% lower with cabozantinib than with everolimus (hazard ratio, 0.58; 95% confidence interval [CI] 0.45 to 0.75; P<0.001). The objective response rate was 21% with cabozantinib and 5% with everolimus (P<0.001). A planned interim analysis showed that overall survival was longer with cabozantinib than with everolimus (hazard ratio for death, 0.67; 95% CI, 0.51 to 0.89; P=0.005) but did not cross the significance boundary for the interim analysis. Adverse events were managed with dose reductions; doses were reduced in 60% of the patients who received cabozantinib and in 25% of those who received everolimus. Discontinuation of study treatment owing to adverse events occurred in 9% of the patients who received cabozantinib and in 10% of those who received everolimus. Progression-free survival was longer with cabozantinib than with everolimus among patients with renal-cell carcinoma that had progressed after VEGFR-targeted therapy. (Funded by Exelixis; METEOR ClinicalTrials.gov number, NCT01865747.).

  8. Orbitofacial Metastatic Basal Cell Carcinoma: Report of 10 Cases.

    PubMed

    Branson, Sara V; McClintic, Elysa; Ozgur, Omar; Esmaeli, Bita; Yeatts, R Patrick

    To explore the clinical features, management, and prognosis of metastatic basal cell carcinoma originating in the orbitofacial region. Ten cases of orbitofacial metastatic basal cell carcinoma were identified by searching databases at 2 institutions from 1995 to 2015. A retrospective chart review was performed. Main outcome measures included patient demographics, lesion size, location of metastases, histologic subtype, recurrence rate, time between primary tumor diagnosis and metastasis, perineural invasion, treatment modalities, and survival from time of metastasis. The median tumor size at largest dimension was 3.3 cm (range, 1.9-11.5 cm), and 6 of 10 patients had at least 1 local recurrence before metastasis (range, 0-2 recurrences). The most common sites of metastasis included the ipsilateral parotid gland (n = 6) and cervical lymph nodes (n = 5). Histologic subtypes included infiltrative (n = 5), basosquamous (n = 2), nodular (n = 1), and mixed (n = 1). The median time from primary tumor diagnosis to metastasis was 7.5 years (range, 0-13). The median survival time from diagnosis of metastasis to last documented encounter or death was 5.3 years (range, 7 months-22.8 years). Treatment regimens included surgical excision, radiotherapy, and hedgehog inhibitors. Based on our findings, the following features may be markers of high risk orbitofacial basal cell carcinoma: 1) increasing tumor size, 2) local recurrence of the primary tumor, 3) aggressive histologic subtype, and 4) perineural invasion. Screening should include close observation of the primary site and tissues in the distribution of regional lymphatics, particularly the parotid gland and cervical lymph nodes.

  9. PT2385 for the Treatment of Von Hippel-Lindau Disease-Associated Clear Cell Renal Cell Carcinoma

    ClinicalTrials.gov

    2017-08-23

    VHL Gene Mutation; VHL; VHL Syndrome; VHL Gene Inactivation; Von Hippel; Von Hippel-Lindau Disease; Von Hippel's Disease; Von Hippel-Lindau Syndrome, Modifiers of; Clear Cell Renal Cell Carcinoma; Clear Cell RCC; ccRCC

  10. Biology of Metastatic Renal Cell Carcinoma

    PubMed Central

    Milella, Michele; Felici, Alessandra

    2011-01-01

    In the past ten years we have made exceptional progresses in the understanding of RCC biology, particularly by recognizing the crucial pathogenetic role of activation of the HIF/VEGF and mTOR pathways. This has resulted in the successful clinical development of anti-angiogenic and mTOR-targeted drugs, which have profoundly impacted on the natural history of the disease and have improved the duration and quality of RCC patient lives. However, further improvements are still greatly needed: 1) even in patients who obtain striking clinical responses early in the course of treatment, disease will ultimately escape control and progress to a treatment-resistant state, leading to therapeutic failure; 2) prolonged disease control usually requires 'continuous' treatment, even across different treatment lines, making the impact of chronic, low-grade, toxicities on quality of life greater and precluding, for most patients, the possibility of experiencing 'drug-free holidays'; 3) although we have successfully identified classes of drugs (or molecular mechanisms of action) that are effective in a substantial proportion of patients, we still fall short of molecular predictive factors that identify individual patients who will (or will not) benefit from a specific intervention and still proceed on a trial-and-error basis, far from a truly 'personalized' therapeutic approach; 4) finally (and perhaps most importantly), even in the best case scenario, currently available treatments inevitably fail to definitively 'cure' metastatic RCC patients. In this review we briefly summarize recent developments in the understanding of the molecular pathogenesis of RCC, the development of resistance/escape mechanisms, the rationale for sequencing agents with different mechanisms of action, and the importance of host-related factors. Unraveling the complex mechanisms by which RCC shapes host microenvironment and immune response and therapeutic treatments, in turn, shape both cancer cell biology

  11. Biology of metastatic renal cell carcinoma.

    PubMed

    Milella, Michele; Felici, Alessandra

    2011-01-01

    In the past ten years we have made exceptional progresses in the understanding of RCC biology, particularly by recognizing the crucial pathogenetic role of activation of the HIF/VEGF and mTOR pathways. This has resulted in the successful clinical development of anti-angiogenic and mTOR-targeted drugs, which have profoundly impacted on the natural history of the disease and have improved the duration and quality of RCC patient lives. However, further improvements are still greatly needed: 1) even in patients who obtain striking clinical responses early in the course of treatment, disease will ultimately escape control and progress to a treatment-resistant state, leading to therapeutic failure; 2) prolonged disease control usually requires 'continuous' treatment, even across different treatment lines, making the impact of chronic, low-grade, toxicities on quality of life greater and precluding, for most patients, the possibility of experiencing 'drug-free holidays'; 3) although we have successfully identified classes of drugs (or molecular mechanisms of action) that are effective in a substantial proportion of patients, we still fall short of molecular predictive factors that identify individual patients who will (or will not) benefit from a specific intervention and still proceed on a trial-and-error basis, far from a truly 'personalized' therapeutic approach; 4) finally (and perhaps most importantly), even in the best case scenario, currently available treatments inevitably fail to definitively 'cure' metastatic RCC patients. In this review we briefly summarize recent developments in the understanding of the molecular pathogenesis of RCC, the development of resistance/escape mechanisms, the rationale for sequencing agents with different mechanisms of action, and the importance of host-related factors. Unraveling the complex mechanisms by which RCC shapes host microenvironment and immune response and therapeutic treatments, in turn, shape both cancer cell biology

  12. Reappraisal of Morphologic Differences Between Renal Medullary Carcinoma, Collecting Duct Carcinoma, and Fumarate Hydratase-deficient Renal Cell Carcinoma.

    PubMed

    Ohe, Chisato; Smith, Steven C; Sirohi, Deepika; Divatia, Mukul; de Peralta-Venturina, Mariza; Paner, Gladell P; Agaimy, Abbas; Amin, Mitual B; Argani, Pedram; Chen, Ying-Bei; Cheng, Liang; Colecchia, Maurizio; Compérat, Eva; Werneck da Cunha, Isabela; Epstein, Jonathan I; Gill, Anthony J; Hes, Ondřej; Hirsch, Michelle S; Jochum, Wolfram; Kunju, Lakshmi P; Maclean, Fiona; Magi-Galluzzi, Cristina; McKenney, Jesse K; Mehra, Rohit; Nesi, Gabriella; Osunkoya, Adeboye O; Picken, Maria M; Rao, Priya; Reuter, Victor E; de Oliveira Salles, Paulo Guilherme; Schultz, Luciana; Tickoo, Satish K; Tomlins, Scott A; Trpkov, Kiril; Amin, Mahul B

    2018-03-01

    Renal medullary carcinomas (RMCs) and collecting duct carcinomas (CDCs) are rare subsets of lethal high-stage, high-grade distal nephron-related adenocarcinomas with a predilection for the renal medullary region. Recent findings have established an emerging group of fumarate hydratase (FH)-deficient tumors related to hereditary leiomyomatosis and renal cell carcinoma (HLRCC-RCCs) syndrome within this morphologic spectrum. Recently developed, reliable ancillary testing has enabled consistent separation between these tumor types. Here, we present the clinicopathologic features and differences in the morphologic patterns between RMC, CDC, and FH-deficient RCC in consequence of these recent developments. This study included a total of 100 cases classified using contemporary criteria and ancillary tests. Thirty-three RMCs (SMARCB1/INI1-deficient, hemoglobinopathy), 38 CDCs (SMARCB1/INI1-retained), and 29 RCCs defined by the FH-deficient phenotype (FH/2SC or FH/2SC with FH mutation, regardless of HLRCC syndromic stigmata/history) were selected. The spectrum of morphologic patterns was critically evaluated, and the differences between the morphologic patterns present in the 3 groups were analyzed statistically. Twenty-five percent of cases initially diagnosed as CDC were reclassified as FH-deficient RCC on the basis of our contemporary diagnostic approach. Among the different overlapping morphologic patterns, sieve-like/cribriform and reticular/yolk sac tumor-like patterns favored RMCs, whereas intracystic papillary and tubulocystic patterns favored FH-deficient RCC. The tubulopapillary pattern favored both CDCs and FH-deficient RCCs, and the multinodular infiltrating papillary pattern favored CDCs. Infiltrating glandular and solid sheets/cords/nested patterns were not statistically different among the 3 groups. Viral inclusion-like macronucleoli, considered as a hallmark of HLRCC-RCCs, were observed significantly more frequently in FH-deficient RCCs. Despite the

  13. Mechanical Stress Promotes Cisplatin-Induced Hepatocellular Carcinoma Cell Death

    PubMed Central

    Riad, Sandra; Bougherara, Habiba

    2015-01-01

    Cisplatin (CisPt) is a commonly used platinum-based chemotherapeutic agent. Its efficacy is limited due to drug resistance and multiple side effects, thereby warranting a new approach to improving the pharmacological effect of CisPt. A newly developed mathematical hypothesis suggested that mechanical loading, when coupled with a chemotherapeutic drug such as CisPt and immune cells, would boost tumor cell death. The current study investigated the aforementioned mathematical hypothesis by exposing human hepatocellular liver carcinoma (HepG2) cells to CisPt, peripheral blood mononuclear cells, and mechanical stress individually and in combination. HepG2 cells were also treated with a mixture of CisPt and carnosine with and without mechanical stress to examine one possible mechanism employed by mechanical stress to enhance CisPt effects. Carnosine is a dipeptide that reportedly sequesters platinum-based drugs away from their pharmacological target-site. Mechanical stress was achieved using an orbital shaker that produced 300 rpm with a horizontal circular motion. Our results demonstrated that mechanical stress promoted CisPt-induced death of HepG2 cells (~35% more cell death). Moreover, results showed that CisPt-induced death was compromised when CisPt was left to mix with carnosine 24 hours preceding treatment. Mechanical stress, however, ameliorated cell death (20% more cell death). PMID:25685789

  14. Actinic cheilitis and squamous cell carcinoma of the lip: clinical, histopathological and immunogenetic aspects.

    PubMed

    Vieira, Renata Aparecida Martinez Antunes Ribeiro; Minicucci, Eliana Maria; Marques, Mariangela Esther Alencar; Marques, Silvio Alencar

    2012-01-01

    Actinic cheilitis is the main precancerous lesion of the lip. Squamous cell carcinoma of the lip is reported together with oral carcinomas in the Brazilian official statistics. Overall, they account for 40% of the head and neck carcinomas. In general, physicians and dentists know little about what causes oral tumor development and progression. Tumor suppressor genes and cell proliferation regulatory proteins play a role in the progression of actinic cheilitis to squamous cell carcinoma and in its biological behavior. Knowledge on prognostic and diagnostic markers has a positive impact on the follow-up of these patients.

  15. Ubiquitin-specific protease 14 regulates cell proliferation and apoptosis in oral squamous cell carcinoma.

    PubMed

    Chen, Xiangyun; Wu, Jingjing; Chen, Yitian; Ye, Dongxia; Lei, Hu; Xu, Hanzhang; Yang, Li; Wu, Yingli; Gu, Wenli

    2016-10-01

    Ubiquitin-specific protease 14, a deubiquitinating enzyme, has been implicated in the tumorigenesis and progression of several cancers, but its role in oral squamous cell carcinoma remains to be elucidated. The aim of this study was to explore the expression pattern and roles of Ubiquitin-specific protease 14 in the occurrence and development of oral squamous cell carcinoma. Interestingly, Ubiquitin-specific protease 14 was overexpressed in oral cancer tissues and cell lines at both mRNA and protein levels. b-AP15, a specific inhibitor of Ubiquitin-specific protease 14, significantly inhibited the growth of cancer cells and increased cell apoptosis in a dose-dependent manner. Moreover, knockdown of Ubiquitin-specific protease 14 by shRNA significantly inhibited the proliferation and migration of cancer cells in vitro. Finally, using a xenograft mouse model of oral squamous cell carcinoma, knockdown of Ubiquitin-specific protease 14 markedly inhibited tumor growth and triggered the cancer cell apoptosis in vivo, supporting previous results. In conclusion, for the first time we have demonstrated the expression pattern of Ubiquitin-specific protease 14 in oral squamous cell carcinoma and verified a relationship with tumor growth and metastasis. These results may highlight new therapeutic strategies for tumor treatment, application of Ubiquitin-specific protease 14 selective inhibitor, such as b-AP15, or knockdown by shRNA. Collectively, Ubiquitin-specific protease 14 could be a potential therapeutic target for oral squamous cell carcinoma patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. 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

  17. Sarcomatoid renal cell carcinoma: Biology and treatment advances.

    PubMed

    Mouallem, Nemer El; Smith, Steven C; Paul, Asit K

    2018-06-01

    Sarcomatoid transformation in renal cell carcinoma, so called sacromatoid RCC (sRCC), is associated with an aggressive behavior and a poor prognosis. Current therapeutic approaches are largely ineffective. Recent studies looking into the genomic and molecular characterization of sRCCs have provided insights into the biology and pathogenesis of this entity. These advances in molecular signatures may help development of effective treatment strategies. We herein present a review of recent developments in the pathology, biology, and treatment modalities in sRCC. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Immunotherapy in Merkel cell carcinoma: role of Avelumab.

    PubMed

    Palla, Amruth R; Doll, Donald

    2018-01-01

    Merkel cell carcinoma (MCC), a rare skin cancer, is associated with high mortality, especially in a metastatic setting. Though conventional chemotherapy with platinum and etoposide has had high response rates, many of the patients have had early relapse without any effective therapy thereafter. Recently, immune check point inhibitors have shown very good durable responses, leading to the approval of a programmed death-ligand 1 inhibitor Avelumab for these patients. We briefly review the epidemiology and immune basis of the pathogenesis of MCC, which therefore explains the excellent response to check point inhibitors, and throw light on future directions of immunotherapy for this cancer.

  19. Immunotherapy in Merkel cell carcinoma: role of Avelumab

    PubMed Central

    Palla, Amruth R; Doll, Donald

    2018-01-01

    Merkel cell carcinoma (MCC), a rare skin cancer, is associated with high mortality, especially in a metastatic setting. Though conventional chemotherapy with platinum and etoposide has had high response rates, many of the patients have had early relapse without any effective therapy thereafter. Recently, immune check point inhibitors have shown very good durable responses, leading to the approval of a programmed death-ligand 1 inhibitor Avelumab for these patients. We briefly review the epidemiology and immune basis of the pathogenesis of MCC, which therefore explains the excellent response to check point inhibitors, and throw light on future directions of immunotherapy for this cancer. PMID:29535979

  20. Novel approach to recurrent cavoatrial renal cell carcinoma.

    PubMed

    Alejo, Jennifer L; George, Timothy J; Beaty, Claude A; Allaf, Mohamad E; Black, James H; Shah, Ashish S

    2012-05-01

    Renal cell carcinoma (RCC) with cavoatrial extension is a rare and complex problem. Complete resection is difficult but correlates with favorable patient outcomes. We present 2 cases of successful reoperative resections of recurrent RCC in patients with level III-IV cavoatrial involvement. We used a thoracoabdominal approach, peripheral cannulation, and hypothermic circulatory arrest. We advocate this novel approach as a successful means of avoiding a more difficult reoperation. Copyright © 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  1. Nevoid basal cell carcinoma syndrome in a black child.

    PubMed

    Hall, J; Johnston, K A; McPhillips, J P; Barnes, S D; Elston, D M

    1998-02-01

    Nevoid basal cell carcinoma syndrome (NBCCS) is rare in black persons. We describe an 11-year-old black boy with NBCCS who presented with exotropia and a painful, expanding, cystic mass in the left posterior alveolar ridge. Further examination revealed odontogenic keratocysts with palmar and plantar pitting. Less than 5% of reported patients with NBCCS are black. To our knowledge, this is the first report of a black patient with NBCCS presenting with exotropia and an impacted molar displaced into the orbit by an odontogenic keratocyst.

  2. [Care of Merkel cell carcinoma and role of the radiotherapy].

    PubMed

    Rehailia-Blanchard, Amel; Pigné, Grégoire; Guy, Jean-Baptiste; Vallard, Alexis; El Meddeb Hamrouni, Anis; Rancoule, Chloé; Magné, Nicolas

    2017-01-01

    Merkel cell carcinoma is a rare neuro-endocrine tumor of skin with a poor prognosis. Data available in literature are scarce. Current treatment for locoregional disease is based on combined treatment by surgery and radiotherapy. However these treatments are controversial. The aim of the present review is to sum up the different available studies and to compare national and international guidelines. Copyright © 2016 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

  3. Chronicle of a pigmented superficial Basal cell carcinoma.

    PubMed

    Caucanas, Marie; Piérard-Franchimont, Claudine; Piérard, Gérald E

    2012-01-01

    Dermoscopic patterns of basal cell carcinoma (BCC) are well defined, but the dynamics of dermoscopic changes in time were apparently never described so far. In this paper, prominent changes were observed over a 8-week period, allowing to establish a close connection between spoke wheel areas and maple leaf-like aspects, through progressive thickening of the former ones. A chronobiological phenomenon ruling synchronous apoptosis in some of the most superficial BCC nests is suggested, leading to a wax and wane process of millimetric crusts, taking part in the spontaneous BCC regression/progression process.

  4. Gingival squamous cell carcinoma masquerading as an aphthous ulcer

    PubMed Central

    Kumari, Prathypaty Santha; Kumar, Gudi Pavan; Bai, Yendluri Durga; Reddy, Eragam Yella Reddy Balaji Naveen

    2013-01-01

    Gingival squamous cell carcinoma (GSCC) is an uncommon condition of the oral cavity. It is seldom associated with classic risk factors of oral cancer and shows a predilection for females. It's close clinical resemblances to various lesions of the oral cavity may make it go unnoticed. This may lead to diagnosis at advanced stages and coupled with the proximity to underlying alveolar bone may result in subsequent morbidity and mortality. A case of GSCC camouflaged as an aphthous ulcer in a middle aged woman is presented. The article highlights the importance of early diagnosis resulting in conservative treatment approaches. PMID:24174737

  5. SOX10-positive salivary gland tumors: a growing list, including mammary analogue secretory carcinoma of the salivary gland, sialoblastoma, low-grade salivary duct carcinoma, basal cell adenoma/adenocarcinoma, and a subgroup of mucoepidermoid carcinoma.

    PubMed

    Hsieh, Min-Shu; Lee, Yi-Hsuan; Chang, Yih-Leong

    2016-10-01

    Transcription factor SRY-related HMG-box 10 (SOX10) is an important marker for melanocytic, schwannian, myoepithelial, and some salivary gland tumors. The aim of this study was to investigate SOX10 expression more thoroughly in the salivary gland neoplasms, including mammary analogue secretory carcinoma and hyalinizing clear cell carcinoma harboring specific genetic rearrangements. A new rabbit monoclonal anti-SOX10 antibody (clone EP268) was used to examine SOX10 expression in 14 different types of salivary gland tumors. We found that acinic cell carcinoma (AciCC), adenoid cystic carcinoma, mammary analogue secretory carcinoma (MASC), epithelial-myoepithelial carcinoma, low-grade salivary duct carcinoma, sialoblastoma, basal cell adenocarcinoma, basal cell adenoma, and pleomorphic adenoma were SOX10 positive. Salivary duct carcinoma, lymphoepithelial carcinoma, hyalinizing clear cell carcinoma, and oncocytoma were SOX10 negative. Earlier, mucoepidermoid carcinoma (MEC) was considered a SOX10-negative tumor. This study identified a subgroup of SOX10-positive MEC cases with characteristic polygonal epithelial cells, pale-to-eosinophilic cytoplasm, and colloid-like dense eosinophilic material. Our data show SOX10 expression can be observed in salivary gland tumors with either one of the 4 cell types: acinic cells, cuboidal ductal cells with low-grade cytologic features, basaloid cells, and myoepithelial cells. In this article we thoroughly evaluated SOX10 expression in salivary gland tumors. SOX10 is useful in the differential diagnosis between myoepithelial carcinoma with clear cell features and hyalinizing clear cell carcinoma. It can also be used to discriminate low-grade salivary duct carcinoma from high-grade ones. Pathologists should be cautious with the interpretation of SOX10 positivity in salivary gland tumors, and correlation with histologic feature is mandatory. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Neutrophils suppress intraluminal NK-mediated tumor cell clearance and enhance extravasation of disseminated carcinoma cells

    PubMed Central

    Spiegel, Asaf; Brooks, Mary W.; Houshyar, Samin; Reinhardt, Ferenc; Ardolino, Michele; Fessler, Evelyn; Chen, Michelle B.; Krall, Jordan A.; DeCock, Jasmine; Zervantonakis, Ioannis K.; Iannello, Alexandre; Iwamoto, Yoshiko; Cortez-Retamozo, Virna; Kamm, Roger D.; Pittet, Mikael J.; Raulet, David H.; Weinberg, Robert A.

    2016-01-01

    Immune cells promote the initial metastatic dissemination of carcinoma cells from primary tumors. In contrast to their well-studied functions in the initial stages of metastasis, the specific roles of immunocytes in facilitating progression through the critical later steps of the invasion-metastasis cascade remain poorly understood. Here we define novel functions of neutrophils in promoting intraluminal survival and extravasation at sites of metastatic dissemination. We show that CD11b+/Ly6G+ neutrophils enhance metastasis formation via two distinct mechanisms. First, neutrophils inhibit natural killer cell function, which leads to a significant increase in the intraluminal survival time of tumor cells. Thereafter, neutrophils operate to facilitate extravasation of tumor cells through the secretion of IL-1β and matrix metalloproteinases. These results identify neutrophils as key regulators of intraluminal survival and extravasation through their crosstalk with host cells and disseminating carcinoma cells. PMID:27072748

  7. 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.

  8. Evodiamine Induces Cell Growth Arrest, Apoptosis and Suppresses Tumorigenesis in Human Urothelial Cell Carcinoma Cells.

    PubMed

    Shi, Chung-Sheng; Li, Jhy-Ming; Chin, Chih-Chien; Kuo, Yi-Hung; Lee, Ying-Ray; Huang, Yun-Ching

    2017-03-01

    Evodiamine, an indole alkaloid derived from Evodia rutaecarpa, exhibits pharmacological activities including vasodilatation, analgesia, anti-cardiovascular disease, anti-Alzheimer's disease, anti-inflammation, and anti-tumor activity. This study analyzes the anti-tumor effects of evodiamine on cellular growth, tumorigenesis, cell cycle and apoptosis induction of human urothelial cell carcinoma (UCC) cells. The present study showed that evodiamine significantly inhibited the proliferation of UCC cells in a dose- and time-dependent manner. Also, evodiamine suppressed the tumorigenesis of UCC cells in vitro. Moreover, evodiamine caused G 2 /M cell-cycle arrest and induced caspase-dependent apoptosis in UCC cells. Finally, we demonstrated that evodiamine exhibits better cytotoxic than 5-fluorouracil, a clinical chemotherapeutic drug, for UCC cells. Evodiamine induces growth inhibition, tumorigenesis suppression, cell-cycle arrest, and apoptosis induction in human UCC cells. Therefore, this agent displays a therapeutic potential for treating human UCC cells and is worthy for further investigation. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  9. The CXCR5 chemokine receptor is expressed by carcinoma cells and promotes growth of colon carcinoma in the liver.

    PubMed

    Meijer, Joost; Zeelenberg, Ingrid S; Sipos, Bence; Roos, Ed

    2006-10-01

    The chemokine receptor CXCR5 is expressed by B cells and certain T cells and controls their migration into and within lymph nodes. Its ligand BCA-1/CXCL13 is present in lymph nodes and spleen and also in the liver. Surprisingly, we detected CXCR5 in several mouse and human carcinoma cell lines. CXCR5 was particularly prominent in pancreatic carcinoma cell lines and was also detected by immunohistochemistry in 7 of 18 human pancreatic carcinoma tissues. Expression in CT26 colon carcinoma was low in vitro, up-regulated in vivo, and rapidly lost when cells were explanted in vitro. CXCL13 strongly promoted proliferation of CXCR5-transfected CT26 cells in vitro. In the liver, after intrasplenic injection, these CXCR5 transfectants initially grew faster than controls, but the growth rate of control tumors accelerated later to become similar to the transfectants, likely due to the up-regulation of CXCR5. Inhibition of CXCR5 function, by trapping CXCR5 in the endoplasmic reticulum using a CXCL13-KDEL "intrakine," had no effect on initial growth of liver foci but later caused a prolonged growth arrest. In contrast, s.c. and lung tumors of CXCR5- and intrakine-transfected cells grew at similar rates as controls. We conclude that expression of CXCR5 on tumor cells promotes the growth of tumor cells in the liver and, at least for CT26 cells, seems to be required for outgrowth to large liver tumors. Given the limited expression on normal cells, CXCR5 may constitute an attractive target for therapy, particularly for pancreatic carcinoma.

  10. Recent developments in small molecule therapies for renal cell carcinoma.

    PubMed

    Song, Minsoo

    2017-12-15

    Renal cell carcinoma (RCC) is the most common type of kidney cancer in adults and is known to be the 10th most common type of cancer in the world. Most of the currently available RCC drugs are tyrosine kinase inhibitors (TKIs). However, combination therapies of TKIs and immune checkpoint inhibitors such as programmed cell death protein 1 (PD-1) and programmed cell death protein 1 ligand 1 (PD-L1) inhibitors are the focus of most of the final stage clinical trials. Meanwhile, other small molecule therapies for RCC that target indoleamine-2,3-dioxygenase (IDO1), glutaminase, C-X-C chemokine receptor 4 (CXCR4), and transglutaminase 2 (TG2) are emerging as the next generation of therapeutics. In this review, these three major streams for the development of small molecule drugs for RCC are described. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  11. Function of oval cells in hepatocellular carcinoma in rats.

    PubMed

    Fang, Chi-Hua; Gong, Jia-Qing; Zhang, Wei

    2004-09-01

    To study oval cells' pathological characteristics and relationship with the occurrence of hepatocellular carcinoma (HCC); to observe the form and structural characteristics of oval cells; to explore the expression characteristics of C-kit, PCNA mRNA and c-myc gene during the occurrence and development of HCC and the effect of ulinastatin (UTI) on C-kit and PCNA expression. One hundred and twenty-five SD rats fed on 3,3'-diaminobenzidine (DAB) to construct HCC models were divided into control group, cancer-inducing group and UTI intervention group. In each group, rat liver samples were collected at weeks 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22 and 24 respectively to study pathological distribution characteristics of oval cells in the process of carcinogenesis under optical microscope. Oval cells were separated by the methods of improved density gradient centrifugation and their structural characteristics were observed under optical microscope and electronic microscope respectively; the oval cells expressing C-kit and PCNA in the collected samples were observed by the methods of immunohistochemistry and image analysis and the expression of c-myc mRNA was also detected by reverse transcription polymerase chain reaction (RT-PCR). Oval cells proliferated firstly in the portal area then gradually migrated into hepatic parenchyma in the inducing group and intervention group. The oval cells distributed inside and outside the carcinoma nodes. The oval cells presented the characteristics of undifferentiated cells: a high ratio of nucleolus and cellular plasm and obvious nucleoli, rare organelle in plasm. Only a few mitochondria and endoplasmic reticulum and some villus-like apophysis on surface of cells could be seen. Cells stained with C-kit and PCNA antibody were mainly oval cells distributed in the portal area. The expression of c-myc mRNA increased with the progression of HCC. However, in the intervention group, UTI could retard its increase. Oval cells work throughout

  12. Function of oval cells in hepatocellular carcinoma in rats

    PubMed Central

    Fang, Chi-Hua; Gong, Jia-Qing; Zhang, Wei

    2004-01-01

    AIM: To study oval cells pathological characteristics and relationship with the occurrence of hepatocellular carcinoma (HCC); to observe the form and structural characteristics of oval cells; to explore the expression characteristics of C-kit, PCNA mRNA and c-myc gene during the occurrence and development of HCC and the effect of ulinastatin (UTI) on C-kit and PCNA expression. METHODS: One hundred and twenty-five SD rats fed on 3,3'-diaminobenzidine (DAB) to construct HCC models were divided into control group, cancer-inducing group and UTI intervention group. In each group, rat liver samples were collected at weeks 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22 and 24 respectively to study pathological distribution characteristics of oval cells in the process of carcinogenesis under optical microscope. Oval cells were separated by the methods of improved density gradient centrifugation and their structural characteristics were observed under optical microscope and electronic microscope respectively; the oval cells expressing C-kit and PCNA in the collected samples were observed by the methods of immunohistochemistry and image analysis and the expression of c-myc mRNA was also detected by reverse transcription polymerase chain reaction (RT-PCR). RESULTS: Oval cells proliferated firstly in the portal area then gradually migrated into hepatic parenchyma in the inducing group and intervention group. The oval cells distributed inside and outside the carcinoma nodes. The oval cells presented the characteristics of undifferentiated cells: a high ratio of nucleolus and cellular plasm and obvious nucleoli, rare organelle in plasm. Only a few mitochondria and endoplasmic reticulum and some villus-like apophysis on surface of cells could be seen. Cells stained with C-kit and PCNA antibody were mainly oval cells distributed in the portal area. The expression of c-myc mRNA increased with the progression of HCC. However, in the intervention group, UTI could retard its increase

  13. Curcumin targets fibroblast–tumor cell interactions in oral squamous cell carcinoma

    SciTech Connect

    Dudás, József, E-mail: jozsef.dudas@i-med.ac.at; Fullár, Alexandra, E-mail: fullarsz@gmail.com; 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Üllői út 26, 1085 Budapest

    Co-culture of periodontal ligament fibroblasts (PDLs) and SCC-25 oral squamous carcinoma cells (OSCC) results in conversion of PDLs into carcinoma-associated fibroblasts (CAFs) and induces epithelial-to mesenchymal transition (EMT) of OSCC tumor cells. We hypothesized that Curcumin targets this dynamic mutual interaction between CAFs and tumor cells. Normal and 2 μM Curcumin-treated co-culture were performed for 4 days, followed by analysis of tumor cell invasivity, mRNA/protein expression of EMT-markers and mediators, activity measure of matrix metalloproteinase 9 (MMP-9), and western blot analysis of signal transduction in tumor cells and fibroblasts. In Curcumin-treated co-culture, in tumor cells, the levels of nuclear factormore » κB (NFκBα) and early response kinase (ERK)—decreased, in fibroblasts, integrin αv protein synthesis decreased compared to corresponding cells in normal co-culture. The signal modulatory changes induced by Curcumin caused decreased release of EMT-mediators in CAFs and reversal of EMT in tumor cells, which was associated with decreased invasion. These data confirm the palliative potential of Curcumin in clinical application. - Graphical abstract: Co-culture of periodontal ligament fibroblasts (PDLs) and SCC-25 oral squamous carcinoma cells (OSCC) results in conversion of PDLs into carcinoma-associated fibroblasts (CAFs) and induces epithelial-to mesenchymal transition (EMT) of tumor cells. Curcumin targets this dynamic mutual interaction between CAFs and tumor cells by inhibiting the production of EMT mediators in CAFs and by modification of intracellular signaling in tumor cells. This causes less invasivity and reversal of EMT in tumor cells. Highlights: ► Curcumin targets tumor–fibroblast interaction in head and neck cancer. ► Curcumin suppresses mediators of epithelial–mesenchymal transition. ► Curcumin decreases the invasivity of tumor cells.« less

  14. Basal Cell Carcinoma with Myoepithelial Differentiation: Case Report and Literature Review.

    PubMed

    Cohen, Philip R

    2018-01-17

    Basal cell carcinoma is the most common skin cancer. Myoepithelial cells are specialized epithelial cells. Basal cell carcinoma with myoepithelial differentiation is a rare tumor. A 71-year-old man with a basal cell carcinoma with myoepithelial differentiation that presented as an asymptomatic red papule of two months duration on his forehead is described. Including the reported patient, this variant of basal cell carcinoma has been described in 16 patients: 11 men and five women. The patients ranged in age at diagnosis from 43 years to 83 years; the median age at diagnosis was 66 years. All of the tumors were located on the face-most were papules or nodules of less than 10 x 10 mm. Their pathology demonstrated two components: one was that of a typical basal cell carcinoma and the other was myoepithelioma-like in which the tumor cells were plasmacytoid or signet ring in appearance and contained abundant eosinophilic cytoplasm or hyaline inclusions or both. The myoepithelial tumor cells had variable immunohistochemical expression that included not only cytokeratin but also actin, glial fibrillary acid protein, S100, and vimentin. The most common clinical impression, prior to biopsy, was a basal cell carcinoma. The pathologic differential diagnosis included cutaneous mixed sweat gland tumor of the skin, myoepithelioma, myoepithelial carcinoma, and tumors that contain a prominent signet ring cell component (such as metastatic gastrointestinal and breast carcinoma, melanoma, plasmacytoid squamous cell carcinoma, and T-cell lymphoma). Mohs micrographic surgical excision, with complete removal of the tumor, was recommended for treatment of the carcinoma.

  15. Basal Cell Carcinoma with Myoepithelial Differentiation: Case Report and Literature Review

    PubMed Central

    2018-01-01

    Basal cell carcinoma is the most common skin cancer. Myoepithelial cells are specialized epithelial cells. Basal cell carcinoma with myoepithelial differentiation is a rare tumor. A 71-year-old man with a basal cell carcinoma with myoepithelial differentiation that presented as an asymptomatic red papule of two months duration on his forehead is described. Including the reported patient, this variant of basal cell carcinoma has been described in 16 patients: 11 men and five women. The patients ranged in age at diagnosis from 43 years to 83 years; the median age at diagnosis was 66 years. All of the tumors were located on the face—most were papules or nodules of less than 10 x 10 mm. Their pathology demonstrated two components: one was that of a typical basal cell carcinoma and the other was myoepithelioma-like in which the tumor cells were plasmacytoid or signet ring in appearance and contained abundant eosinophilic cytoplasm or hyaline inclusions or both. The myoepithelial tumor cells had variable immunohistochemical expression that included not only cytokeratin but also actin, glial fibrillary acid protein, S100, and vimentin. The most common clinical impression, prior to biopsy, was a basal cell carcinoma. The pathologic differential diagnosis included cutaneous mixed sweat gland tumor of the skin, myoepithelioma, myoepithelial carcinoma, and tumors that contain a prominent signet ring cell component (such as metastatic gastrointestinal and breast carcinoma, melanoma, plasmacytoid squamous cell carcinoma, and T-cell lymphoma). Mohs micrographic surgical excision, with complete removal of the tumor, was recommended for treatment of the carcinoma. PMID:29560294

  16. Culture in embryonic kidney serum and xeno-free media as renal cell carcinoma and renal cell carcinoma cancer stem cells research model.

    PubMed

    Krawczyk, Krzysztof M; Matak, Damian; Szymanski, Lukasz; Szczylik, Cezary; Porta, Camillo; Czarnecka, Anna M

    2018-04-01

    The use of fetal bovine serum hinders obtaining reproducible experimental results and should also be removed in hormone and growth factor studies. In particular hormones found in FBS act globally on cancer cell physiology and influence transcriptome and metabolome. The aim of our study was to develop a renal carcinoma serum free culture model optimized for (embryonal) renal cells in order to select the best study model for downstream auto-, para- or endocrine research. Secondary aim was to verify renal carcinoma stem cell culture for this application. In the study, we have cultured renal cell carcinoma primary tumour cell line (786-0) as well as human kidney cancer stem cells in standard 2D monolayer cultures in Roswell Park Memorial Institute Medium or Dulbecco's Modified Eagle's Medium and Complete Human Kidney Cancer Stem Cell Medium, respectively. Serum-free, animal-component free Human Embryonic Kidney 293 media were tested. Our results revealed that xeno-free embryonal renal cells optimized culture media provide a useful tool in RCC cancer biology research and at the same time enable effective growth of RCC. We propose bio-mimic RCC cell culture model with specific serum-free and xeno-free medium that promote RCC cell viability.

  17. Renal cell carcinoma: incidental detection and pathological staging.

    PubMed

    Siow, W Y; Yip, S K; Ng, L G; Tan, P H; Cheng, W S; Foo, K T

    2000-10-01

    In developed countries, there has been increased incidental detection of renal cell carcinoma (RCC). The incidence, pathological stage and survival of incidentally detected carcinoma in a developing country in Asia where, from 1990 to 1998, 165 renal cell carcinomas were identified. The clinical presentation, diagnostic-imaging modality employed, pathological staging and patient survival was reviewed. Incidental renal cancers included those that were diagnosed through health screening or detected incidentally through imaging studies for other conditions. The survival between these incidentally detected lesions and their symptomatic counterparts (suspected group) was compared. Sixty-four patients (39%) had their tumours detected incidentally, including 39 who were entirely asymptomatic and 25 who presented with non-specific symptoms, not initially suggestive of RCC. For the entire group, computed tomography provided the definitive diagnosis in 81% of cases. The incidental detection group had significantly smaller size of tumour (5.9 cm c.f. 7.6 cm), lower stage and lower histological grading. In particular, 78% of patients with incidental RCC had stage I or II diseases (TNM stage classification), compared with 57% of patients with suspected tumour (p < 0.05; Chi-square test). The disease free survival was significantly better for those with incidental detection (86% c.f. 66% at last follow up; p < 0.05; log-rank test) over a mean follow up period of 33 months (range 1-91). Regression analysis showed that stage of disease was the only independent variable predictive of clinical outcome. In conclusion, that significant numbers of RCC were detected incidentally. These tumours were of a lower clinical pathological stage and had a better prognosis.

  18. Current status of superficial pharyngeal squamous cell carcinoma in Japan.

    PubMed

    Rikitake, Ryoko; Ando, Mizuo; Saito, Yuki; Yoshimoto, Seiichi; Yamasoba, Tatsuya; Higashi, Takahiro

    2017-10-01

    To investigate the status and treatment of superficial pharyngeal squamous cell carcinoma in Japan. We analyzed all cases diagnosed between 2011 and 2013, as recorded in the national database of hospital-based cancer registries. We extracted data on patient sex, age, tumor locations, histology, presentation routes, initial treatments, and TNM stages. Additionally, we compared the characteristics of pharyngeal carcinoma to those of esophageal cancer. A total of 16,521 oropharyngeal and hypopharyngeal cancers from 409 institutions were included. Diagnosis of Tis tumors was infrequent, and both cancers were likely to be diagnosed at an advanced stage (n = 866, 5.3%). Tis diseases were the most commonly detected during follow-up examinations for other diseases (n = 608, 70%). While more oropharyngeal Tis patients were men compared to T1-4 patients (88 vs 82%, respectively), hypopharyngeal cancer patients comprised an equally high proportion of men (94 vs 92%, respectively). The most common location of oropharyngeal Tis tumors was the posterior wall (32%), whereas T1-4 tumors were most commonly found on the lateral wall (36%). In hypopharyngeal cancer, both Tis and T1-4 were most commonly located in the pyriform sinus (62%). The proportion of Tis tumors diagnosed at individual institutions showed a positive correlation with the number of endoscopic treatments (r = 0.32, P < 0.001) and the number of esophageal cancer cases (r = 0.37, P < 0.001). Our national database study elucidated the current characteristics of superficial pharyngeal squamous cell carcinoma patients in Japan. Further improvements in early diagnosis and standardized treatments are warranted.

  19. Cutaneous squamous cell carcinoma in an African pygmy hedgehog (Atelerix albiventris).

    PubMed

    Couture, Émilie L; Langlois, Isabelle; Santamaria-Bouvier, Ariane; Benoit-Biancamano, Marie-Odile

    2015-12-01

    A cutaneous mass was surgically excised in a 4-year-old African pygmy hedgehog (Atelerix albiventris). A squamous cell carcinoma was diagnosed based on histopathological examination and local recurrence following excision is strongly suspected. To the authors' knowledge, this is the first well-documented report of a cutaneous squamous cell carcinoma in this species.

  20. Cutaneous squamous cell carcinoma in an African pygmy hedgehog (Atelerix albiventris)

    PubMed Central

    Couture, Émilie L.; Langlois, Isabelle; Santamaria-Bouvier, Ariane; Benoit-Biancamano, Marie-Odile

    2015-01-01

    A cutaneous mass was surgically excised in a 4-year-old African pygmy hedgehog (Atelerix albiventris). A squamous cell carcinoma was diagnosed based on histopathological examination and local recurrence following excision is strongly suspected. To the authors’ knowledge, this is the first well-documented report of a cutaneous squamous cell carcinoma in this species. PMID:26663924

  1. Basaloid and warty carcinomas of the vulva. Distinctive types of squamous cell carcinoma frequently associated with human papillomaviruses.

    PubMed

    Kurman, R J; Toki, T; Schiffman, M H

    1993-02-01

    In a previous study, we described an elevated prevalence of human papillomavirus (HPV) in two specific types of squamous cell carcinoma of the vulva designated basaloid carcinoma (BC) and warty carcinoma (WC) compared with the conventional type of keratinizing squamous cell carcinoma (KSC). To determine whether there were other differences in their clinical presentation or behavior, we examined 100 cases of squamous cell carcinoma of the vulva classified as BC (28 cases), WC (seven cases), and KSC (65 cases). We included only cases in which tissue adjacent to the tumor was present so that the presence of intraepithelial lesions (squamous hyperplasia, lichen sclerosus, and vulvar intraepithelial neoplasia [VIN]) could be correlated with the different types of invasive carcinomas. Microscopically, BC was characterized by a relatively uniform population of small, ovoid cells with a high nuclear-cytoplasmic ratio resembling VIN 3. Although WC was similar to typical squamous cell carcinoma, it contained many squamous cells that displayed marked nuclear pleomorphism, enlargement, atypia, and multinucleation in conjunction with cytoplasmic cavitation resembling koilocytotic atypia in intraepithelial lesions. The majority of the women with BC and WC were less than 60 years of age, and the proportion of black women was higher as compared with the women with KSC, the majority of whom were white and over 65 years of age. On crude comparison, women with BC appeared to have a survival advantage compared with women with KSC; however, through multivariate modelling, when all possible confounding variables were taken into account, there was little residual impression of a survival advantage of women with BC compared with those having KSC. Substantial differences were found among the three types of carcinoma with regard to the prevalence of adjacent intraepithelial lesions. Squamous hyperplasia was found adjacent to KSC in 54 (83%) of the 65 cases, whereas 27 (77%) of 35 cases of

  2. Revisiting the association between candidal infection and carcinoma, particularly oral squamous cell carcinoma.

    PubMed

    Mohd Bakri, Marina; Mohd Hussaini, Haizal; Rachel Holmes, Ann; David Cannon, Richard; Mary Rich, Alison

    2010-12-21

    Tobacco and alcohol are risk factors associated with cancer of the upper aerodigestive tract, but increasingly the role of infection and chronic inflammation is recognized as being significant in cancer development. Bacteria, particularly Helicobacter pylori, and viruses such as members of the human papilloma virus family and hepatitis B and C are strongly implicated as etiological factors in certain cancers. There is less evidence for an association between fungi and cancer, although it has been recognized for many years that white patches on the oral mucosa, which are infected with Candida, have a greater likelihood of undergoing malignant transformation than those that are not infected. This article reviews the association between the development of oral squamous cell carcinoma in potentially malignant oral lesions with chronic candidal infection and describes mechanisms that may be involved in Candida-associated malignant transformation.

  3. Evaluating the Role of Immunological Cells (Tissue Eosinophils and Mast Cells) in Progression of Oral Squamous Cell Carcinoma.

    PubMed

    Saxena, S; Singh, A; Singh, P; Sundaragiri, K S; Sankhla, B; Bhargava, A

    2018-04-01

    Mast cells and eosinophils are increased in oral squamous cell carcinoma. The significance of such an association has been variably thought to be either a potential diagnostic tool for stromal invasion or as a prognostic indicator. The aim of the study was to study the mast cells and eosinophils between normal oral mucosa, leukoplakia and oral squamous cell carcinoma and to study the significance of mast cells in the progression of the lesion. A retrospective study was done on archival tissue received from January 2015 to December 2015, in the Department of Oral Pathology, RUHS College of Dental Sciences, Jaipur, Rajasthan, India. Seventy (70) cases were studied (30 cases each of leukoplakia and carcinoma and 10 cases of control group), sections were stained with toluidine blue solution to reveal mast cells. Eosinophils were studied in Haematoxylin & Eosin stained sections. Mast cell density significantly increased from: normal mucosa to oral leukoplakia to carcinoma, suggesting a role of the mast cells in the development of these lesions. The higher eosinophil counts in carcinoma group compared to dysplasia group proved that they might have a role in stromal invasion. The assessment of these could become, in the future, useful for therapeutic approaches in this subset of the patient.

  4. Small cell ovarian carcinoma: genomic stability and responsiveness to therapeutics.

    PubMed

    Gamwell, Lisa F; Gambaro, Karen; Merziotis, Maria; Crane, Colleen; Arcand, Suzanna L; Bourada, Valerie; Davis, Christopher; Squire, Jeremy A; Huntsman, David G; Tonin, Patricia N; Vanderhyden, Barbara C

    2013-02-21

    The biology of small cell ovarian carcinoma of the hypercalcemic type (SCCOHT), which is a rare and aggressive form of ovarian cancer, is poorly understood. Tumourigenicity, in vitro growth characteristics, genetic and genomic anomalies, and sensitivity to standard and novel chemotherapeutic treatments were investigated in the unique SCCOHT cell line, BIN-67, to provide further insight in the biology of this rare type of ovarian cancer. The tumourigenic potential of BIN-67 cells was determined and the tumours formed in a xenograft model was compared to human SCCOHT. DNA sequencing, spectral karyotyping and high density SNP array analysis was performed. The sensitivity of the BIN-67 cells to standard chemotherapeutic agents and to vesicular stomatitis virus (VSV) and the JX-594 vaccinia virus was tested. BIN-67 cells were capable of forming spheroids in hanging drop cultures. When xenografted into immunodeficient mice, BIN-67 cells developed into tumours that reflected the hypercalcemia and histology of human SCCOHT, notably intense expression of WT-1 and vimentin, and lack of expression of inhibin. Somatic mutations in TP53 and the most common activating mutations in KRAS and BRAF were not found in BIN-67 cells by DNA sequencing. Spectral karyotyping revealed a largely normal diploid karyotype (in greater than 95% of cells) with a visibly shorter chromosome 20 contig. High density SNP array analysis also revealed few genomic anomalies in BIN-67 cells, which included loss of heterozygosity of an estimated 16.7 Mb interval on chromosome 20. SNP array analyses of four SCCOHT samples also indicated a low frequency of genomic anomalies in the majority of cases. Although resistant to platinum chemotherapeutic drugs, BIN-67 cell viability in vitro was reduced by > 75% after infection with oncolytic viruses. These results show that SCCOHT differs from high-grade serous carcinomas by exhibiting few chromosomal anomalies and lacking TP53 mutations. Although BIN-67 cells are

  5. Characteristics of cell lines established from human colorectal carcinoma.

    PubMed

    Park, J G; Oie, H K; Sugarbaker, P H; Henslee, J G; Chen, T R; Johnson, B E; Gazdar, A

    1987-12-15

    We have characterized 14 human colorectal carcinoma cell lines established from primary and metastatic sites by us during the years 1982 to 1985. Five lines were established in fully defined ACL-4 medium and 9 in serum supplemented R10 medium. However, after establishment, cultures could be grown interchangeably in either medium. The lines grew as floating cell aggregates in ACL-4 medium, while most demonstrated substrate adherence in R10 medium. The lines had relatively long doubling times and low cloning efficiencies. Twelve were tumorigenic in athymic nude mice when injected s.c., and two grew i.p. as well. Based on culture, xenograft, and ultrastructural morphologies, the 14 lines could be subtyped as follows: 4 were well differentiated; 5 were moderately differentiated; 4 were poorly differentiated; and 1 was a mucinous carcinoma. Membrane associated antigens characteristic for gastrointestinal cells (carcinoembryonic antigen, CA 19-9, and TAG-72 antigens) were expressed by 50-71% of the lines. Lines expressing carcinoembryonic antigen and CA 19-9 actively secreted these antigens into the supernatant fluids while TAG-72 antigen was not secreted. Surprisingly, 5 of 7 of the original tumor samples tested and 13 of 14 cultured lines expressed L-dopa decarboxylase activity, which is a characteristic enzyme marker of neuroendocrine cells and tumors. In addition, one poorly differentiated cell line contained dense core granules, characteristic of endocrine secretion. Preliminary cytogenetic analyses indicated that 9 of 11 lines examined contained double minute chromosomes. In addition, 3 of the 9 lines with double minutes also had homogeneously staining regions. These findings indicate a high incidence of amplification of one or more as yet unidentified genes.

  6. Fluorescence detection of oral squamous cell carcinoma using Hyperflav

    NASA Astrophysics Data System (ADS)

    Melnik, Ivan S.; Dets, Sergiy M.; Rawicz, Andrew H.; Zhang, Lewei

    2000-05-01

    A novel hypericin-based drug HyperflavTM has been evaluated for light-induced fluorescence detection of oral cancer. Squamous cell carcinoma was induced with carcinogenic agent in right pouches of forty hamsters (20/20 males/females). Solution of HyperflavTM was sprinkled into stomach with a single dose 0.2 - 4 mg of pure hypericin per kg b.w. and 4 - 8 hours before fluorescence analysis. In two animal groups with cancer symptoms the autofluorescence and hypericin-induced fluorescence were taken under 442 nm excitation. The buccal mucosa and adjacent areas were measured fiberoptically in-vivo and in-vitro using orange/green ratio (610/540). The in-vivo fluorescence imaging of malignant areas was conducted to assist the biopsy guidance and to compare with white-light images. Histological and morphological analyses were performed from biopsies. Oral squamous cell carcinoma in its early stage demonstrated specific higher 610/540 ratio for 37 tested hamsters. Advanced state involved another higher fluorescence maximum around 640 nm that in our opinion caused by strong porphyrin-induced native fluorescence. Such deformation of fluorescence spectra may lead to inadequate perception of diseased tissue area. To avoid this problem the autofluorescence spectra & images were added. HyperflavTM application is promising for demarcation of early oral cancer when combined with autofluorescence measurements.

  7. Silencing of karyopherin α2 inhibits cell growth and survival in human hepatocellular carcinoma

    PubMed Central

    Yang, Yunfeng; Guo, Jian; Hao, Yuxia; Wang, Fuhua; Li, Fengxia; Shuang, Shaomin; Wang, Junping

    2017-01-01

    Karyopherin α2 (KPNA2), involved in nucleocytoplasmic transport, has been reported to be upregulated in hepatocellular carcinoma and considered as a biomarker for poor prognosis. However, comprehensive studies of KPNA2 functions in hepatocellular carcinogenesis are still lacking. Our study examine the roles and related molecular mechanisms of KPNA2 in hepatocellular carcinoma development. Results show that KPNA2 knockdown inhibited the proliferation and growth of hepatocellular carcinoma cells in vitro and in vivo. KPNA2 knockdown also inhibited colony formation ability, induced cell cycle arrest and cellular apoptosis in two hepatocellular carcinoma cell lines, HepG2 and SMMC-7721. Furthermore, gene expression microarray analysis in HepG2 cells with KPNA2 knockdown revealed that critical signaling pathways involved in cell proliferation and survival were deregulated. In conclusion, this study provided systematic evidence that KPNA2 was an essential factor promoting hepatocellular carcinoma and unraveled potential molecular pathways and networks underlying KPNA2-induced hepatocellular carcinogenesis. PMID:28422734

  8. Silencing of karyopherin α2 inhibits cell growth and survival in human hepatocellular carcinoma.

    PubMed

    Yang, Yunfeng; Guo, Jian; Hao, Yuxia; Wang, Fuhua; Li, Fengxia; Shuang, Shaomin; Wang, Junping

    2017-05-30

    Karyopherin α2 (KPNA2), involved in nucleocytoplasmic transport, has been reported to be upregulated in hepatocellular carcinoma and considered as a biomarker for poor prognosis. However, comprehensive studies of KPNA2 functions in hepatocellular carcinogenesis are still lacking. Our study examine the roles and related molecular mechanisms of KPNA2 in hepatocellular carcinoma development. Results show that KPNA2 knockdown inhibited the proliferation and growth of hepatocellular carcinoma cells in vitro and in vivo. KPNA2 knockdown also inhibited colony formation ability, induced cell cycle arrest and cellular apoptosis in two hepatocellular carcinoma cell lines, HepG2 and SMMC-7721. Furthermore, gene expression microarray analysis in HepG2 cells with KPNA2 knockdown revealed that critical signaling pathways involved in cell proliferation and survival were deregulated. In conclusion, this study provided systematic evidence that KPNA2 was an essential factor promoting hepatocellular carcinoma and unraveled potential molecular pathways and networks underlying KPNA2-induced hepatocellular carcinogenesis.

  9. The Analysis of Cell Cycle-related Proteins in Ovarian Clear Cell Carcinoma Versus High-grade Serous Carcinoma.

    PubMed

    Hazama, Yukiko; Moriya, Takuya; Sugihara, Mika; Sano, Rikiya; Shiota, Mitsuru; Nakamura, Takafumi; Shimoya, Koichiro

    2017-10-10

    In Japan, the frequency of ovarian clear cell carcinoma (CCC) is twice as high as that in the United States and Europe. Often, patient prognosis of CCC is poor because of chemoresistance. Here, we focus on the cell cycle, which is one of the mechanisms of chemoresistance. To detect the informative markers and improve the strategy of chemotherapy for CCC, we performed immunochemical staining of cell cycle-related proteins in ovarian malignant tumors. We detected that each of the 29 samples of CCC and high-grade serous carcinoma (HGSC) were necessary to reveal the significant differences in immunostaining and prognosis. We performed the immunostaining analysis using the antibodies of cell cycle-related proteins such as Ki-67, Cdt1, MCM7, and geminin. The positive rate of Cdt1 in the CCC group was significantly higher than that in the HGSC group (P<0.0001). However, the positive rate of geminin in the HGSC group was significantly higher than that in the CCC group (P<0.0001). The overall survival of CCC patients with high labeling index of Cdt1 was significantly worse than that of CCC patients with low labeling index of Cdt1 (P=0.004). The study results suggested that the cancer cells of CCC and HGSC exist in the G1 phase and S, G2, and M phases, respectively. The differences in cell cycle of CCC might be one of the reasons for chemotherapy resistance. Further investigations are necessary to reveal the usefulness of Cdt1 as a biomarker in CCC.

  10. Knockdown of Immature Colon Carcinoma Transcript 1 Inhibits Proliferation and Promotes Apoptosis of Non–Small Cell Lung Cancer Cells

    PubMed Central

    He, Jiantao; Zhang, Shenghui; Yang, Qingbo; Wang, Bo; Liu, Zhiyu; Wu, Xintian

    2016-01-01

    Non–small cell lung cancer, as the most frequent type lung cancer, has lower survival rate of 5 years, despite improvements in surgery and chemotherapy. Previous studies showed immature colon carcinoma transcript 1 is closely related to tumorigenesis of human cancer cells. In the present study, we found immature colon carcinoma transcript 1 was overexpressed in lung cancer tissues using Oncomine database mining, and the biological effect of immature colon carcinoma transcript 1 was investigated in non–small cell lung cancer cell lines 95D and A549. Lentivirus-mediated RNA interference was used to knock down immature colon carcinoma transcript 1 expression in 95D and A549 cells in vitro, and the knockdown efficiency was determined using quantitative real-time polymerase chain reaction and Western blot assay. Knockdown of immature colon carcinoma transcript 1 significantly suppressed non–small cell lung cancer cell proliferation and colony formation ability confirmed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and colony formation assay. Flow cytometry was applied to measure cell cycle arrest, and the result showed the cell cycle arrested in G2/M phase in 95D cells and arrested in G0/G1 phase in A549 cells. Furthermore, we measured the levels of cell cycle–associated proteins by Western blot analysis and found immature colon carcinoma transcript 1–mediated cell proliferation inhibition appeared due to downregulation of cell cycle activator cyclin D1 and upregulation of cell cycle inhibitor p21. In addition, immature colon carcinoma transcript 1 silencing significantly induced non–small cell lung cancer cell apoptosis by annexin V/7-amino-actinomycin D double-staining assay. All our data suggest that immature colon carcinoma transcript 1 may play an important role for non–small cell lung cancer cell proliferation and could be a potential molecular target for diagnosing and treating human non–small cell lung cancer. PMID:27413166

  11. Cytogenetics of small cell carcinoma of the lung.

    PubMed

    Wurster-Hill, D H; Cannizzaro, L A; Pettengill, O S; Sorenson, G D; Cate, C C; Maurer, L H

    1984-12-01

    Nineteen cell lines derived from various malignant tissues of 15 patients with small cell carcinoma of the lung (SCCL) have been studied. The results showed heterogeneity in all cell lines, with no one consistent abnormality among them. Cell lines from 11 of the patients had minute and double minute chromosomes, and cell lines from 2 patients had abnormally banding regions, designated as ABRs, as distinguished from homogeneously staining regions (HSRs). The latter 2 and several of the former cell lines were derived from specimens taken before the patients were placed on therapy. All but 2 of the cell lines had a constant marker load, consisting of 24%-35% of the complement. Some markers remained stable through months and years of culture life, while other markers came and went. Chromosomes #1, #6 and #11 were most frequently involved in marker formation in the cell lines, and these were compared to similar markers in direct bone marrow preparations. Chromosome #1 markers were of variable structure, whereas #6 and #11 most often took the form of 6q- and 11p+ markers, with breakpoints most frequently at 6q23-25 and 11p11-12. A 3p- marker was found in a minority of cell lines. All of these markers were also found in direct marrow preparations from some patients with SCCL. Nonmonoclonal tumors arose from inoculation of bimodal cell lines into nude mice, but population selection by undetermined mechanism was evident. Cytogenetic parameters showed no positive correlation with hormone production by these cell lines.

  12. Squamous cell carcinoma – similarities and differences among anatomical sites

    PubMed Central

    Yan, Wusheng; Wistuba, Ignacio I; Emmert-Buck, Michael R; Erickson, Heidi S

    2011-01-01

    Squamous cell carcinoma (SCC) is an epithelial malignancy involving many anatomical sites and is the most common cancer capable of metastatic spread. Development of early diagnosis methods and novel therapeutics are important for prevention and mortality reduction. In this effort, numerous molecular alterations have been described in SCCs. SCCs share many phenotypic and molecular characteristics, but they have not been extensively compared. This article reviews SCC as a disease, including: epidemiology, pathology, risk factors, molecular characteristics, prognostic markers, targeted therapy, and a new approach to studying SCCs. Through this comparison, several themes are apparent. For example, HPV infection is a common risk factor among the four major SCCs (NMSC, HNSC, ESCC, and NSCLC) and molecular abnormalities in cell-cycle regulation and signal transduction predominate. These data reveal that the molecular insights, new markers, and drug targets discovered in individual SCCs may shed light on this type of cancer as a whole. PMID:21938273

  13. Avelumab and other recent advances in Merkel cell carcinoma.

    PubMed

    Bommareddy, Praveen K; Kaufman, Howard L

    2017-12-01

    Merkel cell carcinoma (MCC) is a rare but aggressive form of skin cancer that occurs in the elderly, is associated with UV radiation and immunosuppression. Initial treatment consists of wide excision with adjuvant radiation. Although the tumor is sensitive to chemotherapy, long-term survival is unusual and there had been no US FDA-approved drugs prior to 2017. The recognition that MCC is associated with the Merkel cell polyomavirus occurs more commonly in immune-compromised patients and tumors express PD-L1 suggested testing immunotherapy. A study of an anti-PD-L1 antibody, avelumab, in chemotherapy-refractory MCC demonstrated a response rate of 31.8% resulting in FDA approval in March 2017 and EMA in September 2017. This review will discuss the disease, role of avelumab and other emerging treatment strategies for MCC.

  14. Renal medullary carcinoma and sickle cell trait: A systematic review.

    PubMed

    Alvarez, Ofelia; Rodriguez, Maria M; Jordan, Lanetta; Sarnaik, Sharada

    2015-10-01

    Sickle cell trait (SCT) carries a small risk of renal medullary carcinoma (RMC). We conducted a systematic literature review and reported new four RMC cases (total N = 217). Eighty eight percent had SCT and 8% had sickle cell disease; 50% were children. Males had 2.4× risk than females. Isolated hematuria or in combination with abdominal or flank pain was the presenting sign in 66% cases. Tumor-related mortality was 95%. Four non-metastatic patients were long-term disease-free survivors. Although risk appears to be very low, individuals with SCT should be informed about the low risk of RMC with the hope of early diagnosis. Hematuria should prompt immediate investigation. © 2015 Wiley Periodicals, Inc.

  15. Merkel cell carcinoma in the community setting: a case report.

    PubMed

    Callaghan, Cameron M; Amornmarn, Rumpa

    2018-04-12

    Merkel cell carcinoma (MCC) is a rare neuroendocrine tumor of the skin initially believed to arise from the Merkel cells. In the community setting a general radiation oncologist may only encounter this pathology in a handful of cases over the course of their career. Due to the low incidence of this malignancy, few prospective randomized controlled trials have ever been conducted and therefore guidelines are based on relatively lower levels of evidence upon which the clinical recommendations are made. We discuss the case of a female in her 90s presenting with a classic MCC primary lesion, as well as satellite lesions proximal to both the primary and the draining regional lymph nodes with no evidence of nodal involvement. Here we discuss the presentation, management, treatment planning, underlying pathology, results and sequelae of treatment. We also review new treatment modalities, and the most current staging systems and guidelines.

  16. Renal cell carcinoma: a review of biology and pathophysiology

    PubMed Central

    Nabi, Shahzaib; Kessler, Elizabeth R.; Bernard, Brandon; Flaig, Thomas W.; Lam, Elaine T.

    2018-01-01

    Over the past decade, our understanding of the biology and pathophysiology of renal cell carcinoma (RCC) has improved significantly. Insight into the disease process has helped us in developing newer therapeutic approaches toward RCC. In this article, we review the various genetic and immune-related mechanisms involved in the pathogenesis and development of this cancer and how that knowledge is being used to develop therapeutic targeted drugs for the treatment of RCC. The main emphasis of this review article is on the most common genetic alterations found in clear cell RCC and how various drugs are currently targeting such pathways. This article also looks at the role of the immune system in allowing the growth of RCC and how the immune system can be manipulated to reactivate cytotoxic immunity against RCC. PMID:29568504

  17. Merkel cell carcinoma: Do you know your guidelines?

    PubMed

    Miles, Brett A; Goldenberg, David

    2016-05-01

    Merkel cell carcinoma (MCC) is a cutaneous neuroendocrine malignancy that exhibits clinically aggressive features and is associated with a poor prognosis. The incidence of MCC seems to be increasing for reasons unknown, and is estimated to be 0.32/100,000 in the United States. This article will review the current literature and National Comprehensive Cancer Network practice guidelines in the treatment of MCC. Resection of MCC with negative margins remains the mainstay of therapy. Positive nodal disease should be treated with neck dissection and adjuvant radiotherapy. High-risk patients should undergo adjuvant radiotherapy, which improves oncologic outcomes. The role of chemotherapy is less clear and is currently reserved for advanced-stage MCC and palliative therapy. The pathogenesis of MCC has recently been impacted with the discovery of the Merkel cell polyomavirus (MCPyV). Research to establish targeted and immunologic therapeutic options are ongoing. © 2015 Wiley Periodicals, Inc.

  18. Textural pattern classification for oral squamous cell carcinoma.

    PubMed

    Rahman, T Y; Mahanta, L B; Chakraborty, C; DAS, A K; Sarma, J D

    2018-01-01

    Despite being an area of cancer with highest worldwide incidence, oral cancer yet remains to be widely researched. Studies on computer-aided analysis of pathological slides of oral cancer contribute a lot to the diagnosis and treatment of the disease. Some researches in this direction have been carried out on oral submucous fibrosis. In this work an approach for analysing abnormality based on textural features present in squamous cell carcinoma histological slides have been considered. Histogram and grey-level co-occurrence matrix approaches for extraction of textural features from biopsy images with normal and malignant cells are used here. Further, we have used linear support vector machine classifier for automated diagnosis of the oral cancer, which gives 100% accuracy. © 2017 The Authors Journal of Microscopy © 2017 Royal Microscopical Society.

  19. HPV-negative penile squamous cell carcinoma: disruptive mutations in the TP53 gene are common.

    PubMed

    Kashofer, Karl; Winter, Elke; Halbwedl, Iris; Thueringer, Andrea; Kreiner, Marisa; Sauer, Stefan; Regauer, Sigrid

    2017-07-01

    The majority of penile squamous cell carcinomas is caused by transforming human papilloma virus (HPV) infection. The etiology of HPV-negative cancers is unclear, but TP53 mutations have been implicated. Archival tissues of 108 invasive squamous cell carcinoma from a single pathology institution in a low-incidence area were analyzed for HPV-DNA and p16 ink4a overexpression and for TP53 mutations by ion torrent next-generation sequencing. Library preparation failed in 32/108 squamous cell carcinomas. Institutional review board approval was obtained. Thirty of 76 squamous cell carcinomas (43%; average 63 years) were HPV-negative with 8/33 squamous cell carcinomas being TP53 wild-type (24%; average 63 years). Twenty-five of 33 squamous cell carcinomas (76%; average 65 years) showed 32 different somatic TP53 mutations (23 missense mutations in exons 5-8, 6 nonsense, 1 frameshift and 2 splice-site mutations). Several hotspot mutations were detected multiple times (R175H, R248, R282, and R273). Eighteen of 19 squamous cell carcinomas with TP53 expression in immunohistochemistry had TP53 mutations. Fifty percent of TP53-negative squamous cell carcinomas showed mostly truncating loss-of-function TP53 mutations. Patients without mutations had longer survival (5 years: 86% vs 61%; 10 years: 60% vs 22%), but valid clinically relevant conclusions cannot be drawn due to different tumor stages and heterogeneous treatment of the cases presented in this study. Somatic TP53 mutations are a common feature in HPV-negative penile squamous cell carcinomas and offer an explanation for HPV-independent penile carcinogenesis. About half of HPV-negative penile cancers are driven by oncogenic activation of TP53, while a quarter is induced by loss of TP53 tumor suppressor function. Detection of TP53 mutations should be carried out by sequencing, as immunohistochemical TP53 staining could not identify all squamous cell carcinomas with TP53 mutations.

  20. Palliative chemotherapy for non-transitional cell carcinomas of the urothelial tract.

    PubMed

    Hong, Jung Yong; Choi, Moon Ki; Uhm, Ji Eun; Park, Min Jae; Lee, Jeeyun; Park, Se Hoon; Park, Joon Oh; Kim, Won Seog; Kang, Won Ki; Lee, Hyun Moo; Choi, Han Yong; Lim, Hoyeong

    2009-01-01

    Non-transitional cell carcinomas of the urothelial tract comprise 5-10% of urothelial cancers. Clinical information regarding the clinical behavior and chemotherapy outcome of non-transitional cell carcinomas of the urothelial tract are incomplete due to their rarity. The object of this study was to evaluate the clinical features and the efficacy of palliative chemotherapy in advanced non-transitional cell carcinomas of the urothelial tract. We analyzed the clinical records of 21 consecutive patients who received palliative chemotherapy for unresectable or metastatic non-transitional cell carcinomas of the urothelial tract between January 1995 and November 2007. All the 21 patients received first-line chemotherapy with platinum-based regimens which are known to be effective in transitional cell urothelial carcinomas. The median age of the patients was 57 years (range, 27-71 years). The primary sites of involvement were the bladder, urethra, urachus, and ureter in 43%, 29%, 19%, and 10% of the patients, respectively. Adenocarcinoma was the most common histological type (67%); squamous cell carcinoma and small cell carcinoma comprised 24 and 10% of the histologic types, respectively. With a median duration of follow-up of 32 months (range, 12-71 months), the median overall survival for all 21 patients from the day of first-line chemotherapy was 13 months (95% CI, 6.8-19.2). The expected 1-year survival rate was 50.6% (95% CI, 28.6-72.5). Univariate analysis showed a better median overall survival in patients with adenocarcinoma, compared to non-adenocarcinomas (47 vs. 10 months, P = 0.049). The median overall survival of patients who received platinum-based palliative chemotherapy for advanced non-transitional cell carcinomas was comparable to previous studies for patients with transitional cell carcinomas. Adenocarcinomas appear to have a favorable prognosis for the survival of the patients who received platinum-based chemotherapy for advanced non-transitional cell

  1. Osthole inhibits the tumorigenesis of hepatocellular carcinoma cells.

    PubMed

    Lin, Zhi-Kun; Liu, Jia; Jiang, Guo-Qiang; Tan, Guang; Gong, Peng; Luo, Hai-Feng; Li, Hui-Min; Du, Jian; Ning, Zhen; Xin, Yi; Wang, Zhong-Yu

    2017-03-01

    Hepatocellular carcinoma (HCC) accounts for approximately 90% of all cases of primary liver cancer, and the majority of patients with HCC are deprived of effective curative methods. Osthole is a Chinese herbal medicine which has been reported to possess various pharmacological functions, including hepatocellular protection. In the present study, we investigated the anticancer activity of osthole using HCC cell lines. We found that osthole inhibited HCC cell proliferation, induced cell cycle arrest, triggered DNA damage and suppressed migration in HCC cell lines. Furthermore, we demonstrated that osthole not only contributed to cell cycle G2/M phase arrest via downregulation of Cdc2 and cyclin B1 levels, but also induced DNA damage via an increase in ERCC1 expression. In addition, osthole inhibited the migration of HCC cell lines by significantly downregulating MMP-2 and MMP-9 levels. Finally, we demonstrated that osthole inhibited epithelial-mesenchymal transition (EMT) via increasing the expression of epithelial biomarkers E-cadherin and β-catenin, and significantly decreasing mesenchymal N-cadherin and vimentin protein expression. These results suggest that osthole may have potential chemotherapeutic activity against HCC.

  2. The effect of L-cysteine and N-acetylcysteine on porphyrin/heme biosynthetic pathway in cells treated with 5-aminolevulinic acid and exposed to radiation.

    PubMed

    He, D; Behar, S; Roberts, J E; Lim, H W

    1996-10-01

    The effects of L-cysteine (LC) and N-acetylcysteine (NAC) on porphyrin accumulation in a human dermal microvascular endothelial cell line (HMEC-1) and a human epidermoid carcinoma cell line (A431) loaded with 5-aminolevulinic acid (ALA) and exposed to ultraviolet A (UVA) and blue light radiation were determined. Porphyrin accumulation was decreased in the presence of 0.1-7.5 mM LC (24.8%-31.4% suppression in HMEC-1 cell; 35.8%-48.9% suppression in A431 cells), and in the presence of 0.1-10.0 mM NAC (30.9%-58.0% suppression in HMEC-1 cells; 8.5%-45.3% in A431 cells). The suppression occurred in a LC or NAC dose-dependent fashion. The above was associated with partial reversal of suppression of ferrochelatase (FeC) activity in HMEC-1 cells and in A431 cells. As compared to FeC activity in cells treated with ALA and irradiation, enzyme activity was higher (by 31.9%-62.1%) in the presence of LC (1.0 mM or 5.0 mM) and in the presence of NAC (1.0 mM or 5.0 mM). These data indicate that LC and NAC have protective effects on porphyrin- and irradiation-induced diminution of FeC activity in HMEC-1 cells and A341 cells in vitro.

  3. Gallic acid modulates phenotypic behavior and gene expression in oral squamous cell carcinoma cells by interfering with leptin pathway.

    PubMed

    Santos, Eliane Macedo Sobrinho; da Rocha, Rogério Gonçalves; Santos, Hércules Otacílio; Guimarães, Talita Antunes; de Carvalho Fraga, Carlos Alberto; da Silveira, Luiz Henrique; Batista, Paulo Ricardo; de Oliveira, Paulo Sérgio Lopes; Melo, Geraldo Aclécio; Santos, Sérgio Henrique; de Paula, Alfredo Maurício Batista; Guimarães, André Luiz Sena; Farias, Lucyana Conceição

    2018-01-01

    Gallic acid is a polyphenolic compost appointed to interfere with neoplastic cells behavior. Evidence suggests an important role of leptin in carcinogenesis pathways, inducing a proliferative phenotype. We investigated the potential of gallic acid to modulate leptin-induced cell proliferation and migration of oral squamous cell carcinoma cell lines. The gallic acid effect on leptin secretion by oral squamous cell carcinoma cells, as well as the underlying molecular mechanisms, was also assessed. For this, we performed proliferation, migration, immunocytochemical and qPCR assays. The expression levels of cell migration-related genes (MMP2, MMP9, Col1A1, and E-cadherin), angiogenesis (HIF-1α, mir210), leptin signaling (LepR, p44/42 MAPK), apoptosis (casp-3), and secreted leptin levels by oral squamous cell carcinoma cells were also measured. Gallic acid decreased proliferation and migration of leptin-treated oral squamous cell carcinoma cells, and reduced mRNA expression of MMP2, MMP9, Col1A1, mir210, but did not change HIF-1α. Gallic acid decreased levels of leptin secreted by oral squamous cell carcinoma cells, accordingly with downregulation of p44/42 MAPK expression. Thus, gallic acid appears to break down neoplastic phenotype of oral squamous cell carcinoma cells by interfering with leptin pathway. Copyright © 2017 Elsevier GmbH. All rights reserved.

  4. VX-970, Cisplatin, and Radiation Therapy in Treating Patients With Locally Advanced HPV-Negative Head and Neck Squamous Cell Carcinoma

    ClinicalTrials.gov

    2018-06-11

    Head and Neck Squamous Cell Carcinoma; Human Papillomavirus Negative; Stage III Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v6 and v7; Stage III Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IV Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v7; Stage IV Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v7; Stage IVA Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v7; Stage IVB Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVC Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v7; Stage IVC Oropharyngeal Squamous Cell Carcinoma AJCC v7

  5. Ursodeoxycholic acid induces apoptosis of hepatocellular carcinoma cells in vitro.

    PubMed

    Zhu, Lei; Shan, Lu Juan; Liu, Yue Jian; Chen, Dan; Xiao, Xiao Guang; Li, Yan

    2014-12-01

    Ursodeoxycholic acid (UDCA) is widely used to treat chronic liver diseases, and its cytoprotective effect on normal hepatocytes has been shown. This study aimed to investigate the apoptotic effects of UDCA on hepatocellular carcinoma (HCC) cells and the underlying molecular events in vitro. HCC cells were treated by UDCA at different doses and periods of time to assess cell morphology, viability, apoptosis and gene expression using methyl thiazolyl tetrazolium (MTT), Annexin V/propidium iodide (PI) stain, transferase dUTP nick end labeling (TUNEL), enzyme-linked immunosorbent assay (ELISA), immunocytochemistry and quantitative reverse transcription polymerase chain reaction, respectively. UDCA treatment reduced cell viability but induced HCC cell apoptosis in dose-dependent and time-dependent manners. UDCA arrested HepG2 cells at phase S of the cell cycle. At the gene levels, UDCA downregulated Bcl-2 and second mitochondria-derived activator of caspase (Smac) protein expressions, but upregulated Bax and Livin proteins in HCC cells. At the highest concentration, UDCA inhibited Livin mRNA expression but increased Smac and caspase-3 mRNA expressions as well as the activity of caspase-3 in HCC cells. The induction of HCC cell apoptosis by UDCA was dose-dependent and time-dependent and was mediated by the regulation of Bax to Bcl-2 ratio, the expressions of Smac and Livin, and caspase-3 expression and activity. © 2014 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

  6. Inhibitory effects of 3-bromopyruvate in human nasopharyngeal carcinoma cells.

    PubMed

    Zou, Xue; Zhang, Mengxiao; Sun, Yiming; Zhao, Surong; Wei, Yingmei; Zhang, Xudong; Jiang, Chenchen; Liu, Hao

    2015-10-01

    Tumor cells depend on aerobic glycolysis for adenosine triphosphate (ATP) production, which is therefore targeted by therapeutic agents. The compound 3-bromopyruvate (3-BrPA), a strong alkylating agent and hexokinase inhibitor, inhibits tumor cell glycolysis and the production of ATP, causing apoptosis. 3-BrPA induces apoptosis of nasopharyngeal carcinoma (NPC) cell lines HNE1 and CNE-2Z, which may be related to its molecular mechanisms. In the present study, we investigated the effects of 3-BrPA on the viability, reactive oxygen species (ROS), apoptosis and other types of programmed cell death in NPC cells in vitro and in vivo. PI staining showed significant apoptosis in NPC cells accompanied by the overproduction of ROS and downregulation of mitochondrial membrane potential (MMP, ΔΨm) by 3-BrPA. However, the ROS scavenger N-acetyl-L-cysteine (NAC) significantly reduced 3-BrPA-induced apoptosis by decreasing ROS and facilitating the recovery of MMP. We elucidated the molecular mechanisms underlying 3-BrPA activity and found that it caused mitochondrial dysfunction and ROS production, leading to necroptosis of NPC cells. We investigated the effects of the caspase inhibitor z-VAD-fmk, which inhibits apoptosis but promotes death domain receptor (DR)-induced NPC cell necrosis. Necrostatin-1 (Nec-1) inhibits necroptosis, apparently via a DR signaling pathway and thus abrogates the effects of z-VAD‑fmk. In addition, we demonstrated the effective attenuation of 3-BrPA-induced necrotic cell death by Nec-1. Finally, animal studies proved that 3-BrPA exhibited significant antitumor activity in nude mice. The present study is the first demonstration of 3-BrPA-induced non-apoptotic necroptosis and ROS generation in NPC cells and provides potential strategies for developing agents against apoptosis‑resistant cancers.

  7. [Cellular architecture of papillary and nonpapillary transitional cell carcinoma].

    PubMed

    Moriyama, M

    1989-07-01

    To characterize the cellular architecture of papillary and nonpapillary transitional cell carcinoma. 2 normal ureters, 6 papillary bladder cancers and 5 nonpapillary bladder cancers were subjected to light and electron microscopic study as well as three dimensional reconstruction by 0.5 microns thick serial sections. Normal urothelium consisted of three cell layers of the basal, intermediate and superficial cells, each of which was morphologically characterized in terms of cell shape and development of cell organelles. Over 90% of the epithelial cells were proved to be connected to the uniform basement membrane directly or with long, fine cytoplasmic processes, forming hemidesmosomes at the junctional portion. Papillary tumors had, as a rule, the same cellular architecture as that of normal epithelium in terms of the regularity of cellular polarity, arrangement and differentiation, and the connection to the basement membrane. But, in G2 tumors, the connection between the intermediate and superficial cells and the basement membrane failed to be confirmed in 7 to 44% of the cells, suggesting the heterogeneity of the tumors. In contrast, nonpapillary tumors showed a high irregularity of the cellular architecture in both lesions of stromal and intra-epithelial invasion. The development of the basement membrane was indefinite, often showing thinning or disruption where occasional cytoplasmic protrusion of the tumor cells into the lamina propria was found. Nearly all of the intermediate and superficial cells in the intraepithelial lesions proved not to communicate with the basement membrane. The present results indicate distinct differences of cellular architecture between the papillary and nonpapillary urothelial tumors, which may reflect not only the growth pattern but also the biological behaviour of the individual tumors.

  8. Basal cell carcinoma: CD56 and cytokeratin 5/6 staining patterns in the differential diagnosis with Merkel cell carcinoma.

    PubMed

    Panse, Gauri; McNiff, Jennifer M; Ko, Christine J

    2017-06-01

    Basal cell carcinoma (BCC) can resemble Merkel cell carcinoma (MCC) on histopathological examination and while CK20 is a useful marker in this differential, it is occasionally negative in MCC. CD56, a sensitive marker of neuroendocrine differentiation, is sometimes used to identify MCC, but has been reportedly variably positive in BCC as well. In contrast, CK5/6 consistently labels BCC but is not expressed in neuroendocrine tumors. We evaluated 20 cases of BCC for the pattern of CD56 and cytokeratin 5/6 (CK5/6) staining, hypothesizing that these 2 stains could differentiate BCC from MCC in difficult cases. Seventeen cases of MCC previously stained with CD56 were also examined. All BCCs showed patchy expression of CD56 except for 2 cases, which showed staining of greater than 70% of tumor. CK5/6 was diffusely positive in all cases of BCC. Fifteen of 17 MCCs were diffusely positive for CD56. The difference in the pattern of CD56 expression between MCC and BCC (diffuse vs patchy, respectively) was statistically significant (P < .05). BCC typically shows patchy CD56 expression and diffuse CK5/6 positivity. These 2 markers can be used to distinguish between BCC and MCC in challenging cases. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Unusual case of small cell gastric carcinoma: case report and literature review.

    PubMed

    Richards, David; Davis, Daniel; Yan, Peisha; Guha, Sushovan

    2011-04-01

    Small cell carcinomas are among the most aggressive, poorly differentiated, and highly malignant of the neuroendocrine tumors (NETs). Of which, small cell gastric carcinoma is a rare small cell neuroendocrine tumor. The purpose of our study was to present this case and perform a comprehensive literature review. We review a case of small cell gastric carcinoma that is particularly unusual in that it occurred in a woman from the US when the majority of cases of small cell gastric carcinoma have been reported in men from East Asia, and more specifically, from Japan. The diagnosis was made after endoscopy revealed a large ulcerated mass in the gastric cardia of Borrmann type 3. Biopsies revealed multiple small basophilic cells underlying the squamous epithelium of the esophagus and cardiac mucosa, indicating the presence of a tumor at the gastroesophageal junction. Immunostaining established the diagnosis with positive stains for chromogranin, synaptophysin, and CD56. Our patient is being treated with chemotherapy, but many different treatment regimens have been tried for small cell gastric carcinoma with variable success. Overall prognosis for small cell gastric carcinoma is dismal. Neuroendocrine tumors in general have variable clinical behaviors and prognosis is dependent on the neuroendocrine tumor type. The adoption of a standardized classification system for neuroendocrine tumors could improve the recognition of infrequently encountered neuroendocrine tumors like small cell gastric carcinoma and will enhance strategies for treatment and thus improve prognosis for patients with these rare and aggressive tumors.

  10. Aggressive Variants of Papillary Thyroid Carcinoma: Hobnail, Tall Cell, Columnar, and Solid.

    PubMed

    Nath, Meryl C; Erickson, Lori A

    2018-05-01

    Papillary thyroid carcinomas are the most common endocrine cancer and are usually associated with good survival. However, some variants of papillary thyroid carcinomas may behave more aggressively than classic papillary thyroid carcinomas. The tall cell variant of papillary thyroid carcinoma is the most common aggressive variant of papillary thyroid carcinoma. The aggressive behavior has been ascribed to the histologic subtype and/or to the clinicopathologic features, an issue that remains controversial. The columnar variant of papillary thyroid carcinoma can be aggressive, particularly in older patients, with larger tumors showing a diffusely infiltrative growth pattern and extrathyroidal extension. A papillary thyroid carcinoma is designated as solid/trabecular variant when all or nearly all of a tumor not belonging to any of the other variants has a solid, trabecular, or nested (insular) appearance. This tumor must be distinguished from poorly differentiated thyroid carcinoma which has the same growth pattern but lacks nuclear features of papillary thyroid carcinoma and may show tumor necrosis and high mitotic activity. New to the fourth edition of the WHO Classification of Tumours of Endocrine Organs, the hobnail variant of papillary thyroid carcinoma is a moderately differentiated papillary thyroid carcinoma variant with aggressive clinical behavior and significant mortality. All of these variants are histologically unique and important to recognize due to their aggressive behavior.

  11. Comparison of clinical characteristics of patients with follicular thyroid carcinoma and Hürthle cell carcinoma.

    PubMed

    Ernaga Lorea, Ander; Migueliz Bermejo, Iranzu; Anda Apiñániz, Emma; Pineda Arribas, Javier; Toni García, Marta; Martínez de Esteban, Juan Pablo; Insausti Serrano, Ana María

    2018-03-01

    Hürthle cell carcinoma (HCC) is an uncommon thyroid cancer historically considered to be a variant of follicular thyroid carcinoma (FTC). The aim of this study was to assess the differences between these groups in terms of clinical factors and prognoses. A total of 230 patients (153 with FTC and 77 with HCC) with a median follow-up of 13.4 years were studied. The different characteristics were compared using SPSS version 20 statistical software. Patients with HCC were older (57.3±13.8 years vs. 44.6±15.2 years; P<.001). More advanced TNM stages were also seen in patients with HCC and a greater trend to distant metastases were also seen in patients with HCC (7.8% vs. 2.7%, P=.078). The persistence/recurrence rate at the end of follow-up was higher in patients with HCC (13% vs. 3.9%, P=.011). However, in a multivariate analysis, only age (hazard ratio [HR] 1.10, confidence interval [CI] 1.04-1.17; P=.001), size (HR 1.43, CI 1.05-1.94; P=.021), and histological subtype (HR 9.79, CI 2.35-40.81; P=.002), but not presence of HCC, were significantly associated to prognosis. HCC is diagnosed in older patients and in more advanced stages as compared to FTC. However, when age, size, and histological subtype are similar, disease-free survival is also similar in both groups. Copyright © 2018 SEEN y SED. Publicado por Elsevier España, S.L.U. All rights reserved.

  12. CUTANEOUS SQUAMOUS CELL CARCINOMA IN A PANTHER CHAMELEON (FURCIFER PARDALIS) AND TREATMENT WITH CARBOPLATIN IMPLANTABLE BEADS.

    PubMed

    Johnson, James G; Naples, Lisa M; Chu, Caroline; Kinsel, Michael J; Flower, Jennifer E; Van Bonn, William G

    2016-09-01

    A 3-yr-old male panther chameleon (Furcifer pardalis) presented with bilateral raised crusted skin lesions along the lateral body wall that were found to be carcinoma in situ and squamous cell carcinoma. Similar lesions later developed on the caudal body wall and tail. A subcutaneous implantable carboplatin bead was placed in the first squamous cell carcinoma lesion identified. Additional new lesions sampled were also found to be squamous cell carcinomas, and viral polymerase chain reaction was negative for papillomaviruses and herpesviruses. Significant skin loss would have resulted from excision of all the lesions, so treatment with only carboplatin beads was used. No adverse effects were observed. Lesions not excised that were treated with beads decreased in size. This is the first description of cutaneous squamous cell carcinoma and treatment with carboplatin implantable beads in a panther chameleon.

  13. Improved method increases sensitivity for circulating hepatocellular carcinoma cells

    PubMed Central

    Liu, Hui-Ying; Qian, Hai-Hua; Zhang, Xiao-Feng; Li, Jun; Yang, Xia; Sun, Bin; Ma, Jun-Yong; Chen, Lei; Yin, Zheng-Feng

    2015-01-01

    AIM: To improve an asialoglycoprotein receptor (ASGPR)-based enrichment method for detection of circulating tumor cells (CTCs) of hepatocellular carcinoma (HCC). METHODS: Peripheral blood samples were collected from healthy subjects, patients with HCC or various other cancers, and patients with hepatic lesions or hepatitis. CTCs were enriched from whole blood by extracting CD45-expressing leukocytes with monoclonal antibody coated-beads following density gradient centrifugation. The remaining cells were cytocentrifuged on polylysine-coated slides. Isolated cells were treated by triple immunofluorescence staining with CD45 antibody and a combination of antibodies against ASGPR and carbamoyl phosphate synthetase 1 (CPS1), used as liver-specific markers, and costained with DAPI. The cell slide was imaged and stained tumor cells that met preset criteria were counted. Recovery, sensitivity and specificity of the detection methods were determined and compared by spiking experiments with various types of cultured human tumor cell lines. Expression of ASGPR and CPS1 in cultured tumor cells and tumor tissue specimens was analyzed by flow cytometry and triple immunofluorescence staining, respectively. RESULTS: CD45 depletion of leukocytes resulted in a significantly greater recovery of multiple amounts of spiked HCC cells than the ASGPR+ selection (Ps < 0.05). The expression rates of either ASGPR or CPS1 were different in various liver cancer cell lines, ranging between 18% and 99% for ASGPR and between 9% and 98% for CPS1. In both human HCC tissues and liver cancer cell lines, there were a few HCC cells that did not stain positive for ASGPR or CPS1. The mixture of monoclonal antibodies against ASGPR and CPS1 identified more HCC cells than either antibody alone. However, these antibodies did not detect any tumor cells in blood samples spiked with the human breast cancer cell line MCF-7 and the human renal cancer cell line A498. ASGPR+ or/and CPS1+ CTCs were detected in 29

  14. Radiosensitization by inhibiting STAT1 in renal cell carcinoma.

    PubMed

    Hui, Zhouguang; Tretiakova, Maria; Zhang, Zhongfa; Li, Yan; Wang, Xiaozhen; Zhu, Julie Xiaohong; Gao, Yuanhong; Mai, Weiyuan; Furge, Kyle; Qian, Chao-Nan; Amato, Robert; Butler, E Brian; Teh, Bin Tean; Teh, Bin S

    2009-01-01

    Renal cell carcinoma (RCC) has been historically regarded as a radioresistant malignancy, but the molecular mechanism underlying its radioresistance is not understood. This study investigated the role of signal transducer and activator of transcription 1 (STAT1), a transcription factor downstream of the interferon-signaling pathway, in radioresistant RCC. The expressions of STAT1 and STAT3 in 164 human clear cell RCC samples, 47 papillary RCC samples, and 15 normal kidney tissue samples were examined by microarray expression profiling and immunohistochemistry. Western blotting was performed to evaluate the total and phosphorylated STAT1 expression in CRL-1932 (786-O) (human clear cell RCC), SKRC-39 (human papillary RCC), CCL-116 (human fibroblast), and CRL-1441 (G-401) (human Wilms tumor). STAT1 was reduced or inhibited by fludarabine and siRNA, respectively, and the effects on radiation-induced cell death were investigated using clonogenic assays. STAT1 expression, but not STAT3 expression, was significantly greater in human RCC samples (p = 1.5 x 10(-8) for clear cell; and p = 3.6 x 10(-4) for papillary). Similarly, the expression of STAT1 was relatively greater in the two RCC cell lines. STAT1 expression was reduced by both fludarabine and siRNA, significantly increasing the radiosensitivity in both RCC cell lines. This is the first study reporting the overexpression of STAT1 in human clear cell and papillary RCC tissues. Radiosensitization in RCC cell lines was observed by a reduction or inhibition of STAT1 signaling, using fludarabine or siRNA. Our data suggest that STAT1 may play a key role in RCC radioresistance and manipulation of this pathway may enhance the efficacy of radiotherapy.

  15. Effects of cholera toxin on human colon carcinoma cell lines.

    PubMed

    Barkla, D H; Whitehead, R H; Hayward, I P

    1992-10-01

    This study reports on changes in morphology and membrane transport in 5 human colon carcinoma cell lines treated with cholera toxin (CT). Three of the cell lines that grew as monolayers (LIM 1215, LIM 1899, LIM 2099) and 1 that grew as floating clumps (LIM 2408) did not show morphological changes after CT treatment. However, cell line LIM 1863 that grows as floating "crypt-like" organoids showed rapid and distinctive changes in morphology and membrane transport after CT treatment. At 1 and 6 hrs after CT treatment, light and transmission electron microscopy revealed rapid dilatation of the central lumen of organoids and the appearance of 2 populations of apical vesicular inclusions. The first population was unusual in being non-membrane bound and limited by fuzzy filamentous material. The second population was membrane bound. Scanning electron microscopy at 1-6 hr after CT treatment showed swelling and loss of surface microvilli on some, but not all, cells. At 24 hr after CT treatment the majority of organoids showed evidence of fluid accumulation and small apical vesicles coalesced to form large single vacuoles that obliterated normal cell morphology. By 48 hr, continued swelling produced extreme attenuation of the plasma membrane with cells taking on an "endothelial cell-like" appearance. The response to CT was dose-dependent. Uptake studies using 86Rubidium and blocking studies using ouabain and amiloride indicated that CT is acting on the Na+/K+ ATPase membrane pump to cause the increased fluid uptake by LIM 1863 cells. This study is the first to report specific morphological changes in intestine-derived cells in response to CT.(ABSTRACT TRUNCATED AT 250 WORDS)

  16. [Epidemiology and risk factors of the esophageal squamous cell carcinoma].

    PubMed

    Szumiło, Justyna

    2009-01-01

    Esophageal carcinoma is the eighth most common malignancy in the world. In most countries, including Poland, the squamous cell carcinoma is a predominant histological type. It is characterized by extreme diversity in geographical distribution and incidence. High incidence is noted in regions located along with so-called "Asian esophageal cancer belt" beginning from eastern Turkey through Caspian littoral countries, northern Afghanistan to Central and Eastern Asia, as well as in Japan, South Africa and some South American countries. In Western Europe the highest incidence is observed in France, Portugal and northern Italy. Poland belongs to low-incidence countries with the age-standardized annual incidence exceeding 4.5 and 0.7/100,000, for men and women respectively. Etiology of the cancer is multi-factorial. In western countries the most important risk factors are tobacco smoking and alcohol consumption, and to a lesser extent, an inappropriate diet. In other countries, a diet lacking of fresh vegetables and fruits with vitamin and mineral deficiency and high level of sodium chloride, carbohydrates and animal fats is a predominant factor. Furthermore, preserving and processing food which facilitates accumulation of carcinogens, special dietary habits and viral infections are also attributed to the development of cancer. More recently, the significance of genetically determined increased susceptibility of some individuals versus environmental factors has been stressed. Previous studies proved the relationship between cancer susceptibility and polymorphisms in genes encoding some important molecules engaged in carcinogens metabolism or DNA repair.

  17. [Small-cell anaplastic neuroendocrine carcinoma of the rectum].

    PubMed

    Molas, G; Bougis-de-Brux, M A; Potet, F

    1987-12-01

    A pediculed tumor of the rectum was discovered in a 63 years old man. Within the tumor adenomatous dysplastic proliferation was associated with a neuroendocrine small-cell anaplastic carcinoma. The neuroendocrine nature of the tumor was suspected on conventional optic microscopy and confirmed by a positive Grimelius technique. Specific typical granules were also found on electron microscopy. Immunohistochemical techniques using neurospecific enolase were also positive. Carcinomatous invasion was limited to the submucosa, but the surgical specimen showed that one lymph node was metastatic. Three months later, hepatic metastasis was suspected on physical examination and the patient died of hepatic failure ten months after the discovery of the tumor. Twenty-two similar cases were found in the literature: of these five cases were associated with benign adenomatous lesions. In all cases the patients died of early metastatic diffusion. This tumor raises the problems of diagnosis, terminology, classification and therapy: only aggressive chemotherapy, similar to that applied to the same type of carcinoma in the respiratory tract might improve prognosis.

  18. Salivary analytes in patients with oral squamous cell carcinoma.

    PubMed

    Fuchs, Petra Nola; Rogić, Dunja; Vidović-Juras, Danica; Susić, Mato; Milenović, Aleksandar; Brailo, Vlaho; Boras, Vanja Vucićević

    2011-06-01

    Literature data indicates that measurement of certain salivary constituents might serve as a useful diagnostic/prognostic tool in the patients with oral squamous cell carcinoma (OSCC). In 24 patients with OSCC (60 +/- 2.5 yrs) and in 24 controls (24 +/- 3.7 yrs) we have determined levels of salivary magnesium, calcium, copper, chloride, phosphate, potassium, sodium, total proteins and amylase. Sodium, potassium and chloride were determined by indirect potentiometry whereas copper, magnesium and phosphate were determined by atomic absorption spectrophotometry. Total proteins were determined by pyrogalol colorimetric method. Amylase levels were determined by continued colorimetric method. Statistical analysis was performed by use of chi2 test and Spearman's correlation test. The results of this study indicate that the concentrations of sodium and chloride were significantly elevated in patients with OSCC when compared to the controls. However, level of total protein was significantly decreased when compared to the healthy controls. Furthermore, there was a negative correlation between alcohol consumption and total protein concentration in patients with oral carcinoma. We might conclude that in patients with OSCC increased salivary sodium and chloride might reflect their overall dehydration status due to alcohol consumption rather than consequence of OSCC itself.

  19. Photodynamic therapy in early esophageal squamous cell carcinoma

    NASA Astrophysics Data System (ADS)

    Spinelli, Pasquale; Dal Fante, Marco; Mancini, Andrea; Massetti, Renato; Meroni, Emmanuele

    1995-03-01

    From 1/1985 to 7/1993, 18 patients underwent endoscopic photodynamic therapy (PDT) for early stage esophageal squamous cell carcinoma -- as two patients had two synchronous esophageal cancers, 20 lesions were treated. Tumors were staged as Tis in 7 cases and T1 in 13. The average light energy delivered was 50 J/cm2 and 70 J/cm2 for the treatment of Tis and T1, respectively. To obtain a more uniform distribution of laser light in 12 cases the irradiation was performed through the wall of a transparent tube previously placed over the endoscope and advanced into the stomach. The overall results show a complete response in 14/20 (70%) tumors. Three patients developed a local recurrence, 6, 12, and 14 months after therapy. After a follow-up of 5 to 75 months, there was no evidence of disease in 10/18 patients (56%). The actuarial survival rate was 95%, 79%, and 26% at 1, 3, and 5 years, respectively. Complications were skin reaction in one patient and esophageal stenosis at the treatment site, that gradually responded to endoscopic bougienage, in 2 patients. Endoscopic PDT proved to be safe and effective in the treatment of superficial carcinoma of the esophagus.

  20. 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.

  1. Squamous cell carcinoma antigen in human liver carcinogenesis.

    PubMed

    Guido, M; Roskams, T; Pontisso, P; Fassan, M; Thung, S N; Giacomelli, L; Sergio, A; Farinati, F; Cillo, U; Rugge, M

    2008-04-01

    Squamous cell carcinoma antigen (SCCA) is a serine protease inhibitor that can be overexpressed in hepatocellular carcinoma (HCC) at both molecular and protein level, but no data are available on its expression in pre-malignant stages. To assess SCCA expression by immunohistochemistry in HCC and its nodular precursors in cirrhotic livers. 55 nodules from 42 explanted livers were evaluated: 7 large regenerative nodules (LRNs), 7 low-grade dysplastic nodules (LG-DNs), 10 high-grade DNs (HG-DNs), and 31 HCC. SCCA expression was semiquantitatively scored on a four-tiered scale. SCCA hepatocyte immunostaining was always restricted to the cytoplasm, mainly exhibiting a granular pattern. Stain intensity varied, ranging from weak to very strong. Within the nodules, positive cells were unevenly distributed, either scattered or in irregular clusters. The prevalence of SCCA expression was 29% in LRNs, 100% in DNs and 93% in HCC. A significant difference emerged in both prevalence and score for LRNs versus LG-DNs (p<0.039), HG-DNs (p = 0.001), and HCC (p = 0.000). A barely significant difference (p = 0.49) was observed between LG-DNs and HG-DNs, while no difference in SCCA expression was detected between HG-DNs and HCC. Cirrhotic tissue adjacent to the nodules was positive in 96% of cases, with a significant difference in the score (p = 0.000) between hepatocytes adjacent to HCC and those surrounding LRNs. This study provides the first evidence that aberrant SCCA expression is an early event in liver cell carcinomatous transformation.

  2. Mucin profiles in signet-ring cell carcinoma.

    PubMed

    Nguyen, Minh D; Plasil, Brian; Wen, Ping; Frankel, Wendy L

    2006-06-01

    Signet-ring cell carcinoma (SRCC) is a poorly differentiated mucin-producing adenocarcinoma that may arise from many different organs, but all SRCCs share identical morphology. It is not possible to differentiate sites of origin for metastatic SRCC based on morphology alone. Mucins are high-molecular-weight glycoproteins differentially expressed in glandular epithelia and in adenocarcinomas. To identify mucin profiles of primary and metastatic SRCCs using immunohistochemistry to determine whether mucin staining could help distinguish sites of origin. Forty-seven SRCCs, including 38 primary (21 stomach, 11 colorectum, and 6 breast) and 9 metastases from these primary sites were retrieved from archival files. Consecutive tissue sections were immunostained with monoclonal antibodies against MUC1, MUC2, MUC4, MUC5AC (MUC5), and MUC6 on separate slides. Cytoplasmic staining was scored based on proportion of positive tumor cells as follows: 0+ (<5%), 1+ (5%-25%), 2+ (26%-50%), and 3+ (>50%). Mucin profiles were recorded as MUC+, MUCv, and MUC- for consistent, variable, and negative expression, respectively. The mucin profiles for gastric, colorectum, and breast SRCCs are MUC1.2.4.5.6v, MUC2.4+/MUC5v/ MUC1.6-, and MUC1+/MUC2.5.6v/MUC4-, respectively. Mucin profiles of metastatic cases shared profiles with their respective primaries. Signet-ring cell carcinomas of the stomach, colorectum, and breast have distinct mucin expression patterns that are maintained in metastases. Mucin profiling may be useful to identify the origin of a metastatic SRCC of unknown primary.

  3. Definitive radiation therapy for squamous cell carcinoma of the vagina

    SciTech Connect

    Frank, Steven J.; Jhingran, Anuja; Levenback, Charles

    2005-05-01

    Purpose: To evaluate outcome and describe clinical treatment guidelines for patients with primary squamous cell carcinoma of the vagina treated with definitive radiation therapy. Methods and Materials: Between 1970 and 2000, a total of 193 patients were treated with definitive radiation therapy for squamous cell carcinoma of the vagina at The University of Texas M. D. Anderson Cancer Center. The patients' medical records were reviewed to obtain information about patient, tumor, and treatment characteristics, as well as outcome and patterns of recurrence. Surviving patients were followed for a median of 137 months. Survival rates were calculated using the Kaplan-Meier method,more » with differences assessed using log-rank tests. Results: Disease-specific survival (DSS) and pelvic disease control rates correlated with International Federation of Gynecology and Obstetrics (FIGO) stage and tumor size. At 5 years, DSS rates were 85% for the 50 patients with Stage I, 78% for the 97 patients with Stage II, and 58% for the 46 patients with Stage III-IVA disease (p = 0.0013). Five-year DSS rates were 82% and 60% for patients with tumors {<=}4 cm or >4 cm, respectively (p = 0.0001). At 5 years, pelvic disease control rates were 86% for Stage I, 84% for Stage II, and 71% for Stage III-IVA (p = 0.027). The predominant mode of relapse after definitive radiation therapy was local-regional (68% and 83%, respectively, for patients with stages I-II or III-IVA disease). The incidence of major complications was correlated with FIGO stage; at 5 years, the rates of major complications were 4% for Stage I, 9% for Stage II, and 21% for Stage III-IVA (p < 0.01). Conclusions: Excellent outcomes can be achieved with definitive radiation therapy for invasive squamous cell carcinoma of the vagina. However, to achieve these results, treatment must be individualized according to the site and size of the tumor at presentation and the response to initial external-beam radiation therapy

  4. RNA editing is induced by type I interferon in esophageal squamous cell carcinoma.

    PubMed

    Zhang, Jinyao; Chen, Zhaoli; Tang, Zefang; Huang, Jianbing; Hu, Xueda; He, Jie

    2017-07-01

    In recent years, abnormal RNA editing has been shown to play an important role in the development of esophageal squamous cell carcinoma, as such abnormal editing is catalyzed by ADAR (adenosine deaminases acting on RNA). However, the regulatory mechanism of ADAR1 in esophageal squamous cell carcinomas remains largely unknown. In this study, we investigated ADAR1 expression and its association with RNA editing in esophageal squamous cell carcinomas. RNA sequencing applied to esophageal squamous cell carcinoma clinical samples showed that ADAR1 expression was correlated with the expression of STAT1, STAT2, and IRF9. In vitro experiments showed that the abundance of ADAR1 protein was associated with the induced activation of the JAK/STAT pathway by type I interferon. RNA sequencing results showed that treatment with type I interferon caused an increase in the number and degree of RNA editing in esophageal squamous cell carcinoma cell lines. In conclusion, the activation of the JAK/STAT pathway is a regulatory mechanism of ADAR1 expression and causes abnormal RNA editing profile in esophageal squamous cell carcinoma. This mechanism may serve as a new target for esophageal squamous cell carcinoma therapy.

  5. A dural metastatic small cell carcinoma of the gallbladder as the first manifestation: a case report.

    PubMed

    Tonomura, Shuichi; Kitaichi, Tomoko; Onishi, Rina; Kakehi, Yoshiaki; Shimizu, Hisao; Shimada, Keiji; Kanemasa, Kazuyuki; Fukusumi, Akio; Takahashi, Nobuyuki

    2018-03-16

    A dural metastasis is one of the essential differential diagnoses of meningioma. In general, carcinomas of the breast and lung in females and prostate in males have been the most commonly reported primary lesions of dural metastases. However, dural metastasis of gallbladder carcinoma is extremely rare. Here, we report a unique case of a dural matter metastasis of gallbladder carcinoma as the first manifestation, which was autopsy-defined as small cell carcinoma. A 78-year-old man came to our hospital complaining of left hemianopia. Brain computed tomography (CT) revealed a sizeable parasagittal dural-based extra-axial tumor. However, the findings for meningioma were atypical by magnetic resonance imaging, suggesting a meningioma mimic. A contrast-enhanced CT scan of the abdomen revealed a large gallbladder carcinoma. The patient opted for the best supportive care and died 2 months later. The post-mortem examination revealed small cell carcinoma in gallbladder carcinoma. Moreover, an immunologically similar carcinoma was detected in the dural metastasis. To the best of our knowledge, this is the first case of a dural metastasis of gallbladder small cell carcinoma. A systemic examination is essential for clinicians when atypical findings of meningioma are observed, suggesting a meningioma mimic. We present this rare case with a review of the literature.

  6. Selective Ablation of Tumor Suppressors in Parafollicular C Cells Elicits Medullary Thyroid Carcinoma.

    PubMed

    Song, Hai; Lin, Chuwen; Yao, Erica; Zhang, Kuan; Li, Xiaoling; Wu, Qingzhe; Chuang, Pao-Tien

    2017-03-03

    Among the four different types of thyroid cancer, treatment of medullary thyroid carcinoma poses a major challenge because of its propensity of early metastasis. To further investigate the molecular mechanisms of medullary thyroid carcinoma and discover candidates for targeted therapies, we developed a new mouse model of medullary thyroid carcinoma based on our CGRP CreER mouse line. This system enables gene manipulation in parafollicular C cells in the thyroid, the purported cells of origin of medullary thyroid carcinoma. Selective inactivation of tumor suppressors, such as p53 , Rb , and Pten , in mature parafollicular C cells via an inducible Cre recombinase from CGRP CreER led to development of murine medullary thyroid carcinoma. Loss of Pten accelerated p53 / Rb -induced medullary thyroid carcinoma, indicating interactions between pathways controlled by tumor suppressors. Moreover, labeling differentiated parafollicular C cells by CGRP CreER allows us to follow their fate during malignant transformation to medullary thyroid tumor. Our findings support a model in which mutational events in differentiated parafollicular C cells result in medullary thyroid carcinoma. Through expression analysis including RNA-Seq, we uncovered major signaling pathways and networks that are perturbed following the removal of tumor suppressors. Taken together, these studies not only increase our molecular understanding of medullary thyroid carcinoma but also offer new candidates for designing targeted therapies or other treatment modalities. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  7. Renal Cell Carcinoma, Unclassified with Medullary Phenotype and Synchronous Renal Clear Cell Carcinoma Present in a Patient with No Sickle Cell Trait/Disease: Diagnostic and Therapeutic Challenges.

    PubMed

    Lai, Jenny Z; Lai, H Henry; Cao, Dengfeng

    2018-06-01

    Renal medullary carcinoma (RMC) is an aggressive high-grade renal cell carcinoma (RCC) associated almost exclusively with sickle cell trait or sickle cell disease. However, RCC with RMC features has rarely been reported in patients with no sickle cell trait or disease. Renal cell carcinoma unclassified with medullary phenotype (RCCU-MP) is a newly-coined term used by an international panel of experts to describe renal cell carcinoma showing morphologic and immunohistochemical features of renal medullary carcinoma in patients without sickle cell trait/disease. So far, only one study in the English literature has described five such cases. Here, we report a case with unique clinical and pathological features in a 76-year-old male patient without sickle cell trait. The patient had a history of colon cancer with liver and lung metastases and was found to have a new renal mass in his right kidney during the follow up. A right nephrectomy was performed and showed two separate masses (tumor 1 and tumor 2). Tumor 1 had histologic features of RMC and the tumor cells were positive for CK7, Pax8, and OCT4 and showed loss of nuclear INI1 expression. Tumor 1 was diagnosed as RCCU-MP (6.3 cm, pT3aNx, WHO/ISUP nuclear grade 3). Tumor 2 showed features of clear cell type of RCC (0.6 cm, pT1aNx, WHO/ISUP grade 2) with intact nuclear INI1 expression. Three-months post-nephrectomy, the patient developed lung metastasis of RCCU-MP. To the best of our knowledge, this was the first documented case with synchronous RCCU-MP and clear cell RCC presenting in a patient without sickle cell trait. Careful histologic assessment with a panel of immunohistochemical biomarkers was helpful to render a correct diagnosis for early aggressive treatment. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  8. Expression of Ulex europaeus agglutinin I lectin-binding sites in squamous cell carcinomas and their absence in basal cell carcinomas. Indicator of tumor type and differentiation.

    PubMed

    Heng, M C; Fallon-Friedlander, S; Bennett, R

    1992-06-01

    Lectins bind tightly to carbohydrate moieties on cell surfaces. Alterations in lectin binding have been reported to accompany epidermal cell differentiation, marking alterations in membrane sugars during this process. The presence of UEA I (Ulex europaeus agglutinin I) L-fucose-specific lectin-binding sites has been used as a marker for terminally differentiated (committed) keratinocytes. In this article, we report the presence of UEA-I-binding sites on squamous keratinocytes of well-differentiated squamous cell carcinomas, with patchy loss of UEA I positivity on poorly differentiated cells of squamous cell carcinomas, suggesting a possible use for this technique in the rapid assessment of less differentiated areas within the squamous cell tumor. The absence of UEA-I-binding sites on basal cell carcinomas may be related to an inability of cells comprising this tumor to convert the L-D-pyranosyl moiety on basal cells to the L-fucose moiety, resulting in an inability of basal cell carcinoma cell to undergo terminal differentiation into a committed keratinocyte.

  9. ALA-PpIX variability quantitatively imaged in A431 epidermoid tumors using in vivo ultrasound fluorescence tomography and ex vivo assay

    NASA Astrophysics Data System (ADS)

    DSouza, Alisha V.; Flynn, Brendan P.; Gunn, Jason R.; Samkoe, Kimberley S.; Anand, Sanjay; Maytin, Edward V.; Hasan, Tayyaba; Pogue, Brian W.

    2014-03-01

    Treatment monitoring of Aminolevunilic-acid (ALA) - Photodynamic Therapy (PDT) of basal-cell carcinoma (BCC) calls for superficial and subsurface imaging techniques. While superficial imagers exist for this purpose, their ability to assess PpIX levels in thick lesions is poor; additionally few treatment centers have the capability to measure ALA-induced PpIX production. An area of active research is to improve treatments to deeper and nodular BCCs, because treatment is least effective in these. The goal of this work was to understand the logistics and technical capabilities to quantify PpIX at depths over 1mm, using a novel hybrid ultrasound-guided, fiber-based fluorescence molecular spectroscopictomography system. This system utilizes a 633nm excitation laser and detection using filtered spectrometers. Source and detection fibers are collinear so that their imaging plane matches that of ultrasound transducer. Validation with phantoms and tumor-simulating fluorescent inclusions in mice showed sensitivity to fluorophore concentrations as low as 0.025μg/ml at 4mm depth from surface, as presented in previous years. Image-guided quantification of ALA-induced PpIX production was completed in subcutaneous xenograft epidermoid cancer tumor model A431 in nude mice. A total of 32 animals were imaged in-vivo, using several time points, including pre-ALA, 4-hours post-ALA, and 24-hours post-ALA administration. On average, PpIX production in tumors increased by over 10-fold, 4-hours post-ALA. Statistical analysis of PpIX fluorescence showed significant difference among all groups; p<0.05. Results were validated by exvivo imaging of resected tumors. Details of imaging, analysis and results will be presented to illustrate variability and the potential for imaging these values at depth.

  10. Regulation of carcinoma cell invasion by protein C inhibitor whose expression is decreased in renal cell carcinoma.

    PubMed

    Wakita, Toshiaki; Hayashi, Tatsuya; Nishioka, Junji; Tamaru, Hiroshi; Akita, Nobuyuki; Asanuma, Kunihiro; Kamada, Haruhiko; Gabazza, Esteban C; Ido, Masaru; Kawamura, Juichi; Suzuki, Koji

    2004-02-10

    Protein C inhibitor (PCI), a member of the serine protease inhibitor family, is produced in various human tissues, including the liver, kidney and testis. In addition to inhibiting the anticoagulant protein C pathway, PCI also inhibits urinary plasminogen activator (uPA), which is a well-known mediator of tumor cell invasion. In the present study, to clarify the biologic significance of PCI in the kidney, we compared the expression of PCI between human renal cell carcinoma (RCC) tissue and nontumor kidney tissue. The PCI antigen level in RCC tissue was found to be significantly lower than in nontumor kidney tissue, and expression of PCI mRNA was detected in normal renal proximal tubular epithelial cells (RPTEC), but not in RCC or in an RCC cell line (Caki-1 cells). No differences were detected between the nucleotide sequence of the major cis-elements in the promoter region of the PCI gene from nontumor kidney and RCC tissues, RPTEC and Caki-1 cells, an RPTEC-derived RCC cell line. The in vitro invasiveness of Caki-1 cells transfected with a PCI expression vector was significantly decreased compared to mock-transfected Caki-1 cells, and it was blocked in the presence of anti-PCI antibody. Since PCI itself did not affect the proliferation rate of Caki-1 cells or cell expression of uPA in vitro, the effect of uPA, PCI, heat-inactivated PCI and plasminogen activator inhibitor (PAI)-1 on the invasive potential of cultured RCC cells was evaluated. The in vitro invasiveness of Caki-1 cells, which express uPA, was significantly enhanced by the addition of uPA, and it was inhibited by anti-uPA antibody, PCI and PAI-1, but not by heat-inactivated PCI. In addition, uPA activity was significantly decreased and uPA-PCI complex level was significantly increased in the culture medium of PCI expression vector-transfected Caki-1 cells as compared to mock-transfected Caki-1 cells. These findings strongly suggest that PCI regulates the invasive potential of RCC cells by inhibiting u

  11. Collective cell migration of thyroid carcinoma cells: a beneficial ability to override unfavourable substrates.

    PubMed

    Lobastova, Liudmila; Kraus, Dominik; Glassmann, Alexander; Khan, Dilaware; Steinhäuser, Christian; Wolff, Christina; Veit, Nadine; Winter, Jochen; Probstmeier, Rainer

    2017-02-01

    Tumor cell invasion and metastasis are life threatening events. Invasive tumor cells tend to migrate as collective sheets. In the present in vitro study we aimed to (i) assess whether collective tumor cells gain benefits in their migratory potential compared to single cells and (ii) to identify its putative underlying molecular mechanisms. The migratory potential of single and collective carcinoma cells was assessed using video time lapse microscopy and cell migration assays in the absence and presence of seven potential gap junction inhibitors or the Rac1 inhibitor Z62954982. The perturbation of gap junctions was assessed using a dye diffusion assay. In addition, LDH-based cytotoxicity and RT-PCR-based expression analyses were performed. Whereas single breast, cervix and thyroid carcinoma cells were virtually immobile on unfavourable plastic surfaces, we found that they gained pronounced migratory capacities as collectives under comparable conditions. Thyroid carcinoma cells, that were studied in more detail, were found to express specific subsets of connexins and to form active gap junctions as revealed by dye diffusion analysis. Although all potential gap junction blockers suppressed intercellular dye diffusion in at least one of the cell lines tested, only two of them were found to inhibit collective cell migration and none of them to inhibit single cell migration. In the presence of the Rac1 inhibitor Z62954982 collective migration, but not single cell migration, was found to be reduced up to 20 %. Our data indicate that collective migration enables tumor cells to cross otherwise unfavourable substrate areas. This capacity seems to be independent of intercellular communication via gap junctions, whereas Rac1-dependent intracellular signalling seems to be essential.

  12. 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.

  13. 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

  14. Expression of CDK6 in Oral Squamous Cell Carcinomas

    PubMed

    Andisheh-Tadbir, Azadeh; Ashraf, Mohammad Javad; Jeiroodi, Naghmeh

    2018-04-25

    Background: CDK6 is the key factor in regulation of the cell cycle and essential for passage into the G1 phase. It also plays an important role in the development of various tumors. In this cross-sectional study expression of the CDK6 protein in oral squamous cell carcinoma (OSCC) and healthy oral mucosa of controls was assessed to determine relations with malignant transformation and clinicopathologic factors. Method: A total of 60 samples, 45 from OSCCs and 15 from healthy tissue, underwent immunohistochemistry for CDK6. Nuclear and cytoplasmic staining of keratinocytes was considered as positive and the percentages of positive cells were calculated. Results: Expression of CDK6 was detected in 55.6% of OSCC samples (25 cases) and 13.3% of controls (2 cases), the difference being significant. Mean percentage of CDK6 stained cells was 24.2±29.3 in the OSCC cases and 4.33±2.1 in the control group, again statistically significant. No relationship was detected between CDK6 expression and clinicopathologic factors. Conclusion: Overexpression of CDK6 observed in OSCC points to a role for this protein in oral carcinogenesis. Creative Commons Attribution License

  15. Downregulation of FOXP2 promoter human hepatocellular carcinoma cell invasion.

    PubMed

    Yan, Xia; Zhou, Huiling; Zhang, Tingting; Xu, Pan; Zhang, Shusen; Huang, Wei; Yang, Linlin; Gu, Xingxing; Ni, Runzhou; Zhang, Tianyi

    2015-12-01

    Hepatocellular carcinoma (HCC) is a major health concern with a high morbidity and mortality rate worldwide. However, the mechanism underlying hepatocarcinogenesis remains unclear. Forkhead box P2 (FOXP2) has been implicated in various human cancer types. However, the role of FOXP2 in HCC remains unknown. Western blot and immunohistochemistry were used to measure the expression of FOXP2 protein in HCC and adjacent normal tissues in 50 patients. Wound healing and transwell assays were used to determine the cell invasion ability. We showed that the level of FOXP2 was significantly reduced in HCC compared with the adjacent non-tumorous tissue. There was statistical significance between the expression of FOXP2 and vein invasion (P = 0.017), number of tumor nodes (P = 0.028), and AFP (P = 0.033). Low expression of FOXP2 correlated with poor survival. Moreover, wound healing and transwell assays showed that FOXP2 could decrease cell invasion and affect the expression of vimentin and E-cadherin. Our results suggested that FOXP2 expression was downregulated in HCC tumor tissues, and reduced FOXP2 expression was associated with poor overall survival. In addition, downregulation of FOXP2 significantly enhanced cell invasiveness. These findings uncover that FOXP2 might be a new prognostic factor and be closely correlated with HCC cell invasion.

  16. Prognostic significance of phosphorylated RON in esophageal squamous cell carcinoma.

    PubMed

    Hui, Marco K C; Lai, Kenneth K Y; Chan, Kwok Wah; Luk, John M; Lee, Nikki P; Chung, Yvonne; Cheung, Leo C; Srivastava, Gopesh; Tsao, Sai Wah; Tang, Johnny C; Law, Simon

    2012-09-01

    Esophageal squamous cell carcinoma (ESCC) is the most common type of esophageal cancer. RON is a transmembrane receptor overexpressed in various cancers; however, the clinical significance of its phosphorylated form (pRON) is not fully deciphered. This report is the first to investigate the expression and clinical significance of pRON in human ESCC. Quantitative polymerase chain reaction revealed an up-regulation of RON mRNA in 70% (7/10) of ESCC tissues when compared to the adjacent nontumor tissues. An overexpression of pRON protein was found in most of the ESCC cell lines studied (4/5) when compared to two non-neoplastic esophageal epithelial cells using immunoblot. In 64 ESCC tissues, pRON was localized at the cell membrane, cytoplasm and nucleus in 15 (23.4%), 63 (98.4%) and 61 (95.3%) cases using immunohistochemistry. Patients having high expression of cytoplasmic pRON significantly associated with shorter median survival when compared to those with low expression (25.41 months vs. 14.43 months), suggesting cytoplasmic pRON as a potential marker for poor prognosis in ESCC patients.

  17. FOXF2 promoter methylation is associated with prognosis in esophageal squamous cell carcinoma.

    PubMed

    Chen, Xiaoying; Hu, Haochang; Liu, Jing; Yang, Yong; Liu, Guili; Ying, Xiuru; Chen, Yingmin; Li, Bin; Ye, Cong; Wu, Dongping; Duan, Shiwei

    2017-02-01

    Esophageal squamous cell carcinoma is a commonly malignant tumor of digestive tract with poor prognosis. Previous studies suggested that forkhead box F2 ( FOXF2) could be a candidate gene for assessing and predicting the prognosis of human cancers. However, the relationship between FOXF2 promoter methylation and the prognosis of esophageal squamous cell carcinoma remained unclear. Formalin-fixed, paraffin-embedded esophageal squamous cell carcinoma tissues of 135 esophageal squamous cell carcinoma patients were detected for FOXF2 promoter methylation status by methylation-specific polymerase chain reaction approach. DNA methylation results were evaluated with regard to clinicopathological features and overall survival. Our study confirmed that FOXF2 promoter hypermethylation could independently predict a poorer overall survival of esophageal squamous cell carcinoma patients ( p = 0.002), which was consistent with the data mining results of the data from 82 esophageal squamous cell carcinoma patients in The Cancer Genome Atlas datasets ( p = 0.036). In addition, no correlation was found between FOXF2 promoter methylation and other clinic pathological parameters (age, gender, differentiation, lymph node metastasis, stage, cutting edge, vascular invasion, smoking behavior, and drinking history). In conclusion, FOXF2 methylation might be a useful prognostic biomarker for esophageal squamous cell carcinoma patients.

  18. Role of human papillomavirus in oropharyngeal squamous cell carcinoma: A review

    PubMed Central

    Woods, Robbie SR; O’Regan, Esther M; Kennedy, Susan; Martin, Cara; O’Leary, John J; Timon, Conrad

    2014-01-01

    Human papillomavirus (HPV) has been implicated in the pathogenesis of a subset of oropharyngeal squamous cell carcinoma. As a result, traditional paradigms in relation to the management of head and neck squamous cell carcinoma have been changing. Research into HPV-related oropharyngeal squamous cell carcinoma is rapidly expanding, however many molecular pathological and clinical aspects of the role of HPV remain uncertain and are the subject of ongoing investigation. A detailed search of the literature pertaining to HPV-related oropharyngeal squamous cell carcinoma was performed and information on the topic was gathered. In this article, we present an extensive review of the current literature on the role of HPV in oropharyngeal squamous cell carcinoma, particularly in relation to epidemiology, risk factors, carcinogenesis, biomarkers and clinical implications. HPV has been established as a causative agent in oropharyngeal squamous cell carcinoma and biologically active HPV can act as a prognosticator with better overall survival than HPV-negative tumours. A distinct group of younger patients with limited tobacco and alcohol exposure have emerged as characteristic of this HPV-related subset of squamous cell carcinoma of the head and neck. However, the exact molecular mechanisms of carcinogenesis are not completely understood and further studies are needed to assist development of optimal prevention and treatment modalities. PMID:24945004

  19. Photodynamic detection and treatment of squamous cell carcinoma

    NASA Astrophysics Data System (ADS)

    Vari, Sandor G.; Pergadia, Vani R.; Papaioannou, Thanassis; Snyder, Wendy J.; Marcus, J.; Glassberg, Edward; Dimino-Emme, L.; Fishbein, Michael C.; Thomas, Reem; Dhondt, M. D.; Lask, Gary P.; Grundfest, Warren S.

    1994-02-01

    In this study the fluorescence intensity of photosensitizer in squamous cell tumors were quantified in terms of the tumor resolution rate. A He-Cd laser (442 nm - 17 mW) with a 600 micrometers core silica fiber was used for excitation. The same fiber was used for fluorescence acquisition and an optical multichannel analyzer (EG&G, OMA III) was used to analyze the fluorescence. Twelve days after carcinoma inoculation fluorescence signal from the tumor and skin (1 cm radius from the tumor) at the 12, 3, 6, and 9 o'clock positions were recorded. Benzoporphyrin Derivative (QLT, Canada -- 2 mg/kg of body weight) was then injected into the tail vein. The drug was photoactivated with a 690 nm modified argon pump cw-dye laser (Medtech) operating at 140 mW/cm2 for 15 mins. LIFS is capable of localizing in situ malignancy and evaluating photosensitizers for photodynamic fluorescence detection and therapy of tumors.

  20. 'Dancing eyes, dancing feet syndrome' in small cell lung carcinoma.

    PubMed

    Sharma, Chandramohan; Acharya, Mihir; Kumawat, Bansi Lal; Kochar, Abhishek

    2014-04-23

    A 60-year-old man presented with a 25-day history of acute onset instability of gait, tremulousness of limbs and involuntary eye movements. Examination revealed presence of opsoclonus, myoclonus and ataxia, without any loss of motor power in the limbs. Prompt investigations were directed towards identifying an underlying malignancy which is often associated with this type of clinical scenario. CT of the brain was normal and cerebrospinal fluid examination showed lymphocytic pleocytosis. A cavitatory lesion was found in the right lung base on the high-resolution CT of the chest and histopathological examination of this lung mass showed small cell lung carcinoma. The patient was managed symptomatically with levetiracetam and baclofen and referred to oncology department for resection of the lung mass.

  1. Transitional cell carcinomas in four fishing cats (Prionailurus viverrinus).

    PubMed

    Sutherland-Smith, Meg; Harvey, Catherine; Campbell, Mark; McAloose, Denise; Rideout, Bruce; Morris, Patrick

    2004-09-01

    Transitional cell carcinomas (TCC) of the urinary bladder were diagnosed in four related fishing cats (Prionailurus viverrinus). The major clinical sign in each case was persistent hematuria unresponsive to medical therapy. Cystotomy and biopsy provided an antemortem diagnosis in three of the fishing cats before euthanasia because of progression of clinical signs. The diagnosis was made in the fourth cat after euthanasia because of renal failure. Hematuria improved temporarily in one of the cats diagnosed antemortem and treated with piroxicam and carboplatin. Attempts to isolate a herpesvirus in two of the cats failed. Histopathologic appearance of the TCC was similar to that described for other species. TCC metastasis to the lungs was noted at necropsy in one cat; metastatic disease was not noted in the other fishing cats on gross or histopathologic examination. TCC of the urinary bladder appears to be more prevalent in fishing cats than in other species of domestic or nondomestic felids.

  2. [Squamous cell carcinoma of the nasal vestibule - Review of literature].

    PubMed

    Koopmann, Mario; Rudack, Claudia; Weiss, Daniel; Stenner, Markus

    2018-06-01

    Squamous cell carcinoma of the nasal vestibule is a rare entity. In consequence disagreement in etiology, staging system and therapy of primary tumor with or without adjuvant treatment of regional lymph nodes are apparent. Pubmed-Recherche of relevant literature concerning: lymphatic drainage, metastases, incidence, risk factors (leather, nickel, nicotine, human papillomavirus, Staging system (UICC, AJCC, Wang's system), therapy of the primary tumor, regional lymph nodes and immunohistochemistry. Fifty-five studies were found and analyzed. Results are inconsistent. The Wang-classification is recommended. Radiation and surgery are the treatment of choice for small lesions. Larger lesions (T3-Wang) should be treated with a combined approach. In cT1-cT2cN0-situation after accurate diagnostic, an elective therapy of regional lymph nodes is not necessary. © Georg Thieme Verlag KG Stuttgart · New York.

  3. [Conjunctival squamous cell carcinoma: paradoxical response to interferon eyedrops].

    PubMed

    Mata, E; Conesa, E; Castro, M; Martínez, L; de Pablo, C; González, M L

    2014-07-01

    A 67 year-old male seen for a longstanding corneal-conjunctival tumor. topical interferon α2b (IFN-α2b) 10 U/ml. A significant increase in lesion size was observed after 8 weeks. A surgical excision with cryotherapy was then performed. Pathological examination confirmed the diagnosis of squamous cell carcinoma. At this time the patient was found to have a positive HIV serology. Conjunctival intraepithelial neoplasia (CIN) is a pre-cancerous lesion of the ocular surface. Medical treatment of CIN is essentially with IFN-α2b due to its antiviral/antitumor properties. In patients with HIV, treatment response could be paradoxical. We recommend serology for HIV before treatment with topical IFN-α2b. Copyright © 2012 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.

  4. International cancer seminars: a focus on esophageal squamous cell carcinoma.

    PubMed

    Murphy, G; McCormack, V; Abedi-Ardekani, B; Arnold, M; Camargo, M C; Dar, N A; Dawsey, S M; Etemadi, A; Fitzgerald, R C; Fleischer, D E; Freedman, N D; Goldstein, A M; Gopal, S; Hashemian, M; Hu, N; Hyland, P L; Kaimila, B; Kamangar, F; Malekzadeh, R; Mathew, C G; Menya, D; Mulima, G; Mwachiro, M M; Mwasamwaja, A; Pritchett, N; Qiao, Y-L; Ribeiro-Pinto, L F; Ricciardone, M; Schüz, J; Sitas, F; Taylor, P R; Van Loon, K; Wang, S-M; Wei, W-Q; Wild, C P; Wu, C; Abnet, C C; Chanock, S J; Brennan, P

    2017-09-01

    The International Agency for Research on Cancer (IARC) and the US National Cancer Institute (NCI) have initiated a series of cancer-focused seminars [Scelo G, Hofmann JN, Banks RE et al. International cancer seminars: a focus on kidney cancer. Ann Oncol 2016; 27(8): 1382-1385]. In this, the second seminar, IARC and NCI convened a workshop in order to examine the state of the current science on esophageal squamous cell carcinoma etiology, genetics, early detection, treatment, and palliation, was reviewed to identify the most critical open research questions. The results of these discussions were summarized by formulating a series of 'difficult questions', which should inform and prioritize future research efforts. Published by Oxford University Press on behalf of the European Society for Medical Oncology 2017. This work is written by US Government employees and is in the public domain in the US.

  5. 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.

  6. Avelumab: a new standard for treating metastatic Merkel cell carcinoma.

    PubMed

    Baker, Mairead; Cordes, Lisa; Brownell, Isaac

    2018-04-01

    Merkel cell carcinoma (MCC) is a rare and aggressive skin cancer. Although MCC is chemosensitive, responses to traditional chemotherapeutic agents are not durable. Avelumab, a novel anti-PD-L1 immune checkpoint inhibitor, recently became the first FDA-approved agent for the treatment of metastatic MCC and represents a new option to improve patient survival. Areas covered: This article presents an overview of MCC and summarizes the development of avelumab in the treatment of metastatic MCC. Preclinical studies, phase 1 and phase 2 clinical trials, and the safety profile of avelumab are reviewed. Future perspectives and ongoing studies are also discussed. Expert commentary: Avelumab demonstrated rapid and durable responses and a manageable safety profile in the treatment of metastatic MCC. Patient outcomes are favorable when compared to historical responses to standard chemotherapy. Ongoing clinical trials will continue to characterize avelumab and its optimal use in MCC therapy.

  7. Merkel cell carcinoma: Epidemiology, pathogenesis, diagnosis and therapy.

    PubMed

    Amaral, Teresa; Leiter, Ulrike; Garbe, Claus

    2017-12-01

    Merkel cell carcinoma (MCC) is a rare and aggressive skin cancer with a neuroendocrine phenotype. Incidence varies according to the geographic regions but is overall increasing. Different risk factors have been identified namely advanced age, immunosuppression, and ultraviolet light exposure. An association between MCC and polyomavirus infection is known. However, the exact mechanism that leads to carcinogenesis is yet to be fully understood. Surgery when feasible is the recommended treatment for localized disease, followed by adjuvant radiation or chemoradiation. In the metastatic setting, chemotherapy has been the standard treatment. However, two recently published trials with immune checkpoint inhibitors in first and second line showed promising results with a tolerable safety profile and these might become the standard therapy shortly. Somatostatin receptors are expressed in many MCC but such expression is not associated with disease severity. Presently there are no biomarkers predictive of response that could help to better select patients to these new therapies, and additional research is essential.

  8. Primary Squamous Cell Carcinoma of the Thyroid Gland

    PubMed Central

    Ibrahim, Mohd-Irman-Shah; Jusoh, Yusri-Rahimi; Adam, Nurul-Nadhihah; Mohamad, Irfan

    2018-01-01

    Introduction: Primary squamous cell carcinoma (SCC) of the thyroid gland is one of the rarest types of all reported thyroid malignancies worldwide. It is very aggressive in nature and carries a poor prognosis. The surgical resection with adjuvant radiotherapy and chemotherapy is the most recommended treatment despite its poor reported outcome. Case Report: A 74-year-old woman presented with a rapidly progressive neck swelling, with hoarseness and compressive symptoms. Physical examination revealed a multilobulated firm thyroid mass with unilateral vocal cord palsy. Histopathological findings confirmed the diagnosis of SCC while radiological investigations and panendoscopy findings ruled out the possibility of other primary tumors. A surgical intervention was performed; however, the patient eventually succumbed to death prior to undergoing an oncological treatment. Conclusion: With no standard consensus to guide the management plan, SCC of the thyroid gland presents a great challenge for the managing team to come up with the best treatment option, due to its unfavorable rate of survival. PMID:29387667

  9. Prognostic significance of extensive necrosis in renal cell carcinoma.

    PubMed

    Collins, Jennifer; Epstein, Jonathan I

    2017-08-01

    Few studies using the current classification of renal cell carcinoma (RCC) have looked at a large number of cases with near total necrosis. We identified 21 cases of resections of RCC with >90% necrosis from the archives of Johns Hopkins Hospital between 2000 and 2015. Patients' mean age was 59 years (43-77) with 16 men (76%); 12 cases (57%) were papillary RCC, 4 clear cell papillary RCC (19%), 4 clear cell RCC (19%), and 1 unclassified with sarcomatoid differentiation (5%). International Society of Urological Pathology (ISUP) nucleolar grade was grade 1 (9 cases) or grade 2 (9 cases). Two cases were ISUP nucleolar grade 3, and 1 case was grade 4. Pathological stage was low (pT1-2) in 20 (95%) with the unclassified RCC with sarcomatoid differentiation RCC stage pT3a. Mean tumor size was 6.3 cm (1.2-17). In 52% (11) of cases, it was difficult to identify viable tumor, requiring multiple sections; 4 cases of papillary RCC were diagnosed in part due to necrotic tumor "ghost" architecture. Follow-up was available in 17 cases (81%) with a mean follow-up of 59 months. Thirteen patients (62%) are alive without disease. The patient with unclassified carcinoma with sarcomatoid differentiation died of cancer, and 2 died due to causes unrelated to cancer. One patient (5%) with low-grade clear cell RCC developed metastases but had a contralateral RCC. In the setting of a low-grade RCC, extensive necrosis does not have an adverse prognosis. In summary, our data, together with a prior study from our institution, comprise one of the largest cohorts of extensively (>90%) necrotic RCCs and suggests that in the setting of a low-grade RCC, it portends a good prognosis (only 2/36 cases showing progression (6%) on follow-up). However, we did identify a single case of high-grade RCC with an adverse prognosis and therefore, careful attention to tumor grade and classification is critical. The presence of tumor necrosis as a prognosticator in RCCs is complex, and despite its well

  10. The somatic genomic landscape of chromophobe renal cell carcinoma

    PubMed Central

    Davis, Caleb F.; Ricketts, Christopher; Wang, Min; Yang, Lixing; Cherniack, Andrew D.; Shen, Hui; Buhay, Christian; Kang, Hyojin; Kim, Sang Cheol; Fahey, Catherine C.; Hacker, Kathryn E.; Bhanot, Gyan; Gordenin, Dmitry A.; Chu, Andy; Gunaratne, Preethi H.; Biehl, Michael; Seth, Sahil; Kaipparettu, Benny A.; Bristow, Christopher A.; Donehower, Lawrence A.; Wallen, Eric M.; Smith, Angela B.; Tickoo, Satish K.; Tamboli, Pheroze; Reuter, Victor; Schmidt, Laura S.; Hsieh, James J.; Choueiri, Toni K.; Hakimi, A. Ari; Chin, Lynda; Meyerson, Matthew; Kucherlapati, Raju; Park, Woong-Yang; Robertson, A. Gordon; Laird, Peter W.; Henske, Elizabeth P.; Kwiatkowski, David J.; Park, Peter J.; Morgan, Margaret; Shuch, Brian; Muzny, Donna; Wheeler, David A.; Linehan, W. Marston; Gibbs, Richard A.; Rathmell, W. Kimryn; Creighton, Chad J.

    2014-01-01

    Summary We describe the landscape of somatic genomic alterations of 66 chromophobe renal cell carcinomas (ChRCCs) based on multidimensional and comprehensive characterization, including mitochondrial DNA (mtDNA) and whole genome sequencing. The result is consistent that ChRCC originates from the distal nephron compared to other kidney cancers with more proximal origins. Combined mtDNA and gene expression analysis implicates changes in mitochondrial function as a component of the disease biology, while suggesting alternative roles for mtDNA mutations in cancers relying on oxidative phosphorylation. Genomic rearrangements lead to recurrent structural breakpoints within TERT promoter region, which correlates with highly elevated TERT expression and manifestation of kataegis, representing a mechanism of TERT up-regulation in cancer distinct from previously-observed amplifications and point mutations. PMID:25155756

  11. Salvage treatment for recurrent oropharyngeal squamous cell carcinoma.

    PubMed

    Röösli, Christof; Studer, Gabriela; Stoeckli, Sandro J

    2010-08-01

    This study evaluates the oncological outcome of patients with recurrent oropharyngeal squamous cell carcinoma (OPSCC) after primary radiation therapy +/- chemotherapy, primary surgical therapy, and surgical therapy followed by radiation therapy +/- chemotherapy. A total of 156 patients (36%) of a cohort of 427 treated for OPSCC between 1990 and 2006 developed recurrent disease. Fifty-one patients (12%) qualified for salvage treatment. Study endpoints were 5-year overall survival (OS) and disease-specific survival (DSS). The 5-year OS and DSS rates after salvage treatment were 29% and 40%; after initial primary radiation therapy, 25% and 40%; after initial surgery followed by radiation therapy, 40% and 40%; and after initial surgery alone, 20% and 40%. Patients with an advanced OPSCC have a considerable risk for recurrence. Despite poor ultimate outcome, salvage treatment should be attempted in patients with resectable disease, good performance status, and absence of distant metastases. 2009 Wiley Periodicals, Inc. Head Neck, 2010.

  12. Genetic Susceptibility to Head and Neck Squamous Cell Carcinoma

    SciTech Connect

    Lacko, Martin; Braakhuis, Boudewijn J.M.; Sturgis, Erich M.

    2014-05-01

    Head-and-neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide, and its incidence is growing. Although environmental carcinogens and carcinogenic viruses are the main etiologic factors, genetic predisposition obviously plays a risk-modulating role, given that not all individuals exposed to these carcinogens experience the disease. This review highlights some aspects of genetic susceptibility to HNSCC: among others, genetic polymorphisms in biotransformation enzymes, DNA repair pathway, apoptotic pathway, human papillomavirus-related pathways, mitochondrial polymorphisms, and polymorphism related to the bilirubin-metabolized pathway. Furthermore, epigenetic variations, familial forms of HNSCC, functional assays for HNSCC risk assessment, and the implications and perspectives ofmore » research on genetic susceptibility in HNSCC are discussed.« less

  13. Human Papilloma Virus and Squamous Cell Carcinoma of the Anus

    PubMed Central

    Gami, Bhavna; Kubba, Faris; Ziprin, Paul

    2014-01-01

    The incidence of anal cancer is increasing. In the UK, the incidence is estimated at approximately 1.5 per 100,000. Most of this increase is attributed to certain at-risk populations. Persons who are human immunodeficiency virus (HIV)–positive and men who have sex with men (MSM), Organ transplant recipients, women with a history of cervical cancer, human papilloma virus (HPV), or cervical intraepithelial neoplasia (CIN) are known to have a greater risk for anal cancer. This paper will focus on HPV as a risk factor for anal intraepithelial neoplasia (AIN) and discusses the etiology, anatomy, pathogenesis, management of squamous cell carcinoma (SCC) of the anus. PMID:25288893

  14. Management of periorbital basal cell carcinoma with orbital invasion.

    PubMed

    Sun, Michelle T; Wu, Albert; Figueira, Edwin; Huilgol, Shyamala; Selva, Dinesh

    2015-11-01

    Basal cell carcinoma (BCC) is the most common eyelid malignancy; however, orbital invasion by periocular BCC is rare, and management remains challenging. Established risk factors for orbital invasion by BCC include male gender, advanced age, medial canthal location, previous recurrences, large tumor size, aggressive histologic subtype and perineural invasion. Management requires a multidisciplinary approach with orbital exenteration remaining the treatment of choice. Globe-sparing treatment may be appropriate in selected patients and radiotherapy and chemotherapy are often used as adjuvant therapies for advanced or inoperable cases, although the evidence remains limited. We aim to summarize the presentation and treatment of BCC with orbital invasion to better guide the management of this complex condition.

  15. Novel Hedgehog pathway targets against basal cell carcinoma

    SciTech Connect

    Tang, Jean Y.; Department of Epidemiology and Biostatistics, University of California, San Francisco, CA; So, P.-L.

    2007-11-01

    The Hedgehog signaling pathway plays a key role in directing growth and patterning during embryonic development and is required in vertebrates for the normal development of many structures, including the neural tube, axial skeleton, skin, and hair. Aberrant activation of the Hedgehog (Hh) pathway in adult tissue is associated with the development of basal cell carcinoma (BCC), medulloblastoma, and a subset of pancreatic, gastrointestinal, and other cancers. This review will provide an overview of what is known about the mechanisms by which activation of Hedgehog signaling leads to the development of BCCs and will review two recent papers suggesting thatmore » agents that modulate sterol levels might influence the Hh pathway. Thus, sterols may be a new therapeutic target for the treatment of BCCs, and readily available agents such as statins (HMG-CoA reductase inhibitors) or vitamin D might be helpful in reducing BCC incidence.« less

  16. Nevus sebaceus with basal cell carcinoma, poroma, and verruca vulgaris.

    PubMed

    Cicek, Ali Fuat; Aykan, Andac; Yapici, Abdulkerim; Gamsizkan, Mehmet; Ozturk, Serdar; Demiriz, Murat

    2015-01-01

    Nevus sebaceus (NS) is a congenital, benign, hamartomatous lesion and it is possible to see several benign or malignant tumors accompanying it. One of these is the poroma, which is very rare, and has only been reported twice before, in the English literature. In this paper, we presented two new cases of NS. One of them was a 40-year-old male who presented with a congenital skin lesion on his temporoparietal region. This lesion was composed of four different lesions, including NS, poroma, basal cell carcinoma (BCC), and verruca vulgaris. The second patient was a 41-year-old male presenting with a yellow-brown patch on the scalp. This lesion was comprised of NS and BCC. In addition to these presentations, we discussed the differential diagnosis between BCC and trichoblastoma, both of which are likely to be seen with NS. For this purpose, we recommended an immunohistological panel, which may be useful for differentiating these two morphologically similar lesions.

  17. Treatment of renal cell carcinoma: Current status and future directions.

    PubMed

    Barata, Pedro C; Rini, Brian I

    2017-11-01

    Answer questions and earn CME/CNE Over the past 12 years, medical treatment for renal cell carcinoma (RCC) has transitioned from a nonspecific immune approach (in the cytokine era), to targeted therapy against vascular endothelial growth factor (VEGF), and now to novel immunotherapy agents. Multiple agents-including molecules against vascular endothelial growth factor, platelet-derived growth factor, and related receptors; inhibitors of other targets, such as the mammalian target of rapamycin and the MET and AXL tyrosine-protein kinase receptors; and an immune-checkpoint inhibitor-have been approved based on significant activity in patients with advanced RCC. Despite these advances, important questions remain regarding biomarkers of efficacy, patient selection, and the optimal combination and sequencing of agents. The purpose of this review is to summarize present management and future directions in the treatment of metastatic RCC. CA Cancer J Clin 2017;67:507-524. © 2017 American Cancer Society. © 2017 American Cancer Society.

  18. Lymphatic drainage in renal cell carcinoma: back to the basics.