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Sample records for jnk-dependent epithelial neoplasia

  1. scribble mutants promote aPKC and JNK-dependent epithelial neoplasia independently of Crumbs

    PubMed Central

    Leong, Gregory R; Goulding, Karen R; Amin, Nancy; Richardson, Helena E; Brumby, Anthony M

    2009-01-01

    Background Metastatic neoplasias are characterized by excessive cell proliferation and disruptions to apico-basal cell polarity and tissue architecture. Understanding how alterations in cell polarity can impact upon tumour development is, therefore, a central issue in cancer biology. The Drosophila gene scribble (scrib) encodes a PDZ-domain scaffolding protein that regulates cell polarity and acts as a tumour suppressor in flies. Increasing evidence also implicates the loss of human Scrib in cancer. In this report, we investigate how loss of Scrib promotes epithelial tumourigenesis in Drosophila, both alone and in cooperation with oncogenic mutations. Results We find that genetically distinct atypical protein kinase C (aPKC)-dependent and Jun N-terminal kinase (JNK)-dependent alterations in scrib mutants drive epithelial tumourigenesis. First, we show that over-expression of the apical cell polarity determinants Crumbs (Crb) or aPKC induces similar cell morphology defects and over-proliferation phenotypes as scrib loss-of-function. However, the morphological and proliferative defects in scrib mutants are independent of Crb function, and instead can be rescued by a dominant negative (kinase dead) aPKC transgene. Secondly, we demonstrate that loss of Scrib promotes oncogene-mediated transformation through both aPKC and JNK-dependent pathways. JNK normally promotes apoptosis of scrib mutant cells. However, in cooperation with oncogenic activated Ras or Notch signalling, JNK becomes an essential driver of tumour overgrowth and invasion. aPKC-dependent signalling in scrib mutants cooperates with JNK to significantly enhance oncogene-mediated tumour overgrowth. Conclusion These results demonstrate distinct aPKC and JNK-dependent pathways through which loss of Scrib promotes tumourigenesis in Drosophila. This is likely to have a direct relevance to the way in which human Scrib can similarly restrain an oncogene-mediated transformation and, more generally, on how the

  2. Gastrointestinal epithelial neoplasia: Vienna revisited.

    PubMed

    Dixon, M F

    2002-07-01

    International consensus meetings in Padova and Vienna have attempted to rationalise the grading and classification of gastrointestinal epithelial neoplasia (GEN). With its minor adjustments, the Vienna classification of GEN seeks to be more closely in tune with patient management and it is hoped that it is not seen as fiddling around with terms but as a genuine contribution to patient care.

  3. Human Papillomaviruses; Epithelial Tropisms, and the Development of Neoplasia.

    PubMed

    Egawa, Nagayasu; Egawa, Kiyofumi; Griffin, Heather; Doorbar, John

    2015-07-16

    Papillomaviruses have evolved over many millions of years to propagate themselves at specific epithelial niches in a range of different host species. This has led to the great diversity of papillomaviruses that now exist, and to the appearance of distinct strategies for epithelial persistence. Many papillomaviruses minimise the risk of immune clearance by causing chronic asymptomatic infections, accompanied by long-term virion-production with only limited viral gene expression. Such lesions are typical of those caused by Beta HPV types in the general population, with viral activity being suppressed by host immunity. A second strategy requires the evolution of sophisticated immune evasion mechanisms, and allows some HPV types to cause prominent and persistent papillomas, even in immune competent individuals. Some Alphapapillomavirus types have evolved this strategy, including those that cause genital warts in young adults or common warts in children. These strategies reflect broad differences in virus protein function as well as differences in patterns of viral gene expression, with genotype-specific associations underlying the recent introduction of DNA testing, and also the introduction of vaccines to protect against cervical cancer. Interestingly, it appears that cellular environment and the site of infection affect viral pathogenicity by modulating viral gene expression. With the high-risk HPV gene products, changes in E6 and E7 expression are thought to account for the development of neoplasias at the endocervix, the anal and cervical transformation zones, and the tonsilar crypts and other oropharyngeal sites. A detailed analysis of site-specific patterns of gene expression and gene function is now prompted.

  4. Volumetric imaging of oral epithelial neoplasia by MPM-SHGM: epithelial connective tissue interface (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Pal, Rahul; Yang, Jinping; Qiu, Suimin; Resto, Vicente; McCammon, Susan; Vargas, Gracie

    2016-03-01

    The majority of oral cancers are comprised of oral squamous cell carcinoma in which neoplastic epithelial cells invade across the epithelial connective tissue interface (ECTI). Invasion is preceded by a multi-component process including epithelial hyperproliferation, loss of cell polarity, and remodeling of the extracellular matrix. Multiphoton Autofluorescence Microscopy (MPAM) and Second Harmonic Generation Microscopy (SHGM) show promise for revealing indicators of neoplasia. In particular, volumetric imaging by these methods can reveal aspects of the 3D microstructure that are not possible by other methods and which could both further our understanding of neoplastic transformation and be explored for development of diagnostic approaches in this disease having only 55% 5-year survival rate. MPAM-SHG were applied to reveal the 3D structure of the critical ECTI interface that plays an integral part toward invasion. Epithelial dysplasia was induced in an established hamster model. MPAM-SHGM was applied to lesion sites, using 780 nm excitation (450-600nm emission) for autofluroescence of cellular and extracellular components; 840 nm using 420 nm bandpass filter for SHG. The ECTI surface was identified as the interface at which SHG signal began following the epithelium and was modeled as a 3D surface using Matlab. ECTI surface area and cell features at sites of epithelial expansion where ECTI was altered were measured; Imaged sites were biopsied and processed for histology. ROC analysis using ECTI image metrics indicated the ability to delineate normal from neoplasia with high sensitivity and specificity and it is noteworthy that inflammation did not significantly alter diagnostic potential of MPAM-SHGM .

  5. Combining large area fluorescence with multiphoton microscopy for improved detection of oral epithelial neoplasia (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Pal, Rahul; Yang, Jinping; Qiu, Suimin; McCammon, Susan; Resto, Vicente; Vargas, Gracie

    2016-03-01

    Volumetric Multiphoton Autofluorescence Microscopy (MPAM) and Second Harmonic Generation Microscopy (SHGM) show promise for revealing indicators of neoplasia representing the complex microstructural organization of mucosa, potentially providing high specificity for detection of neoplasia, but is limited by small imaging area. Large area fluorescence methods on the other hand show high sensitivity appropriate for screening but are hampered by low specificity. In this study, we apply MPAM-SHGM following guidance from large area fluorescence, by either autofluorescence or a targeted metabolic fluorophore, as a potentially clinically viable approach for detection of oral neoplasia. Sites of high neoplastic potentially were identified by large area red/green autofluorescence or by a fluorescently labelled deoxy-glucose analog, 2-deoxy-2-[(7-nitro-2,1,3-benzoxadiazol-4-yl)amino]-D-glucose (2-NBDG) to highlight areas of high glucose uptake across the buccal pouch of a hamster model for OSCC. Follow-up MPAM-SHGM was conducted on regions of interests (ROIs) to assess whether microscopy would reveal microscopic features associated with neoplasia to confirm or exclude large area fluorescence findings. Parameters for analysis included cytologic metrics, 3D epithelial connective tissue interface metrics (MPAM-SHGM) and intensity of fluorescence (widefield). Imaged sites were biopsied and processed for histology and graded by a pathologist. A small sample of human ex vivo tissues were also imaged. A generalized linear model combining image metrics from large area fluorescence and volumetric MPAM-SHGM indicated the ability to delineate normal and inflammation from neoplasia.

  6. Genetic Instability in Gastric Epithelial Neoplasias Categorized by the Revised Vienna Classification

    PubMed Central

    Chung, Woo Chul; Jung, Sung Hoon; Lee, Kang Moon; Paik, Chang Nyol; Kwak, Jae Wuk; Jung, Ji Han; Yoo, Jin Young; Lee, Min Kyoung

    2010-01-01

    Background/Aims The aim of this study was to determine the structural chromosomal aberrations, such as loss of heterozygosity (LOH) and microsatellite instability (MSI), at multiple tumor suppressor gene loci in gastric epithelial neoplasia categorized by the revised Vienna classification. Methods All tissue samples were excised by endoscopic mucosal resection. Sixty category 3 (low-grade adenoma) tissue samples and 51 category 4 samples (high-grade adenoma and intramucosal carcinoma with adenoma) were examined at the 7 sets of microsatellite loci linked to the tumor suppressor gene locus. Results For category 3 and 4 tissue samples, there were no differences in the frequencies of LOH-positive chromosomes or the extent of chromosomal loss. The Helicobacter-pylori (H. pylori)-positive rate was significantly higher in MSI-positive category 4 samples than in category 3 samples (p=0.04). The frequency of MSI positivity was significantly higher in category 4 samples than in category 3 samples (p=0.003). Conclusions H. pylori infection is associated with genetic instability of the premalignant lesion. MSI occurs in the early stages of gastric carcinogenesis and its occurrence increases during malignant transformation. Detection of MSI in premalignant gastric lesions may be a surveillant of risk of malignant transformation. PMID:20559519

  7. Immunohistochemical Characterization of Intestinal Neoplasia in Zebrafish (Danio rerio) Indicates Epithelial Origin

    PubMed Central

    Paquette, Colleen E.; Kent, Michael L.; Peterson, Tracy S.; Wang, Rong; Dashwood, Roderick H.; Löhr, Christiane V.

    2015-01-01

    Spontaneous neoplasia of the intestinal tract in sentinel and moribund zebrafish (Danio rerio) is common in some zebrafish facilities. We previously classified these tumors as adenocarcinoma, small-cell carcinoma, or carcinoma otherwise unspecified based on histomorphologic characteristics. Based on histological presentation, the primary differential diagnosis for the intestinal carcinomas was tumor of neuroendocrine cells (e.g., carcinoids). To further characterize the phenotype of the neoplastic cells, select tissue sections were stained with a panel of antibodies directed toward human epithelial (Cytokeratin Wide Spectrum Screening [WSS], AE1/AE3) or neuroendocrine (S100, chromogranin A) markers. We also investigated antibody specificity by Western blot analysis, using a human cell line and zebrafish tissues. Nine of the intestinal neoplasms (64%) stained for AE1/AE3, seven (50%) also stained for WSS. None of the intestinal neoplastic cells were stained for chromogranin A or S100. Endocrine cells of the pituitary gland and neurons and axons of peripheral nerves and ganglia stained for Chromogranin A, whereas perineural and periaxonal cells of peripheral intestinal ganglia, and glial and ependymal cells of the brain stained for S100. Immunohistochemistry for cytokeratins confirmed the majority of intestinal neoplasms in this cohort of zebrafish as carcinomas. PMID:26503773

  8. The association between sexually transmitted pathogens and cervical intra-epithelial neoplasia in a developing community.

    PubMed Central

    Kharsany, A B; Hoosen, A A; Moodley, J; Bagaratee, J; Gouws, E

    1993-01-01

    OBJECTIVE--To determine the association of sexually transmitted pathogens in women with cervical intra-epithelial neoplasia (CIN). SETTING--An urban tertiary referral hospital serving a large indigent developing community. PARTICIPANTS--48 women attending a colposcopy clinic and 49 women attending a family planning clinic. METHODS--Vaginal, endocervical, rectal swab specimens and sera were collected for the detection of sexually transmitted pathogens. Cervical cytology was performed on all patients. Women attending the colposcopy clinic had confirmation of abnormal cervical cytology by colposcopic directed biopsy. RESULTS--The mean age of women with CIN (33 years) was significantly greater than that of the women without CIN (28 years) and that of the family planning group (26 years). There was a high prevalence of sexually transmitted pathogens in all women. A significantly higher prevalence of bacterial vaginosis was found in women with CIN compared to those without (50% vs 20%; p = 0.034). The human papilloma virus (HPV) was detected in 46% of women with CIN and 65% of those without CIN. Chlamydia trachomatis (21%) and Trichomonas vaginalis (39%) were detected frequently in women with CIN. C. trachomatis (14%-21%) was detected more frequently than Neisseria gonorrhoeae (3-5%) in all asymptomatic women studied. CONCLUSION--This study demonstrates a high prevalence of sexually transmitted pathogens in women with and without CIN as well as family planning clinic attenders. Bacterial vaginosis was a significant finding in women with CIN. C. trachomatis was detected in a high proportion of all women studied and found more commonly than N. gonorrhoeae. We therefore recommend that all women attending gynaecological services in a developing community be investigated and treated for sexually transmitted diseases. PMID:8244352

  9. Evaluation of HPV Infection and Smoking Status Impacts on Cell Proliferation in Epithelial Layers of Cervical Neoplasia

    PubMed Central

    Guillaud, Martial; Buys, Timon P. H.; Carraro, Anita; Korbelik, Jagoda; Follen, Michele; Scheurer, Michael; Storthz, Karen Adler; van Niekerk, Dirk; MacAulay, Calum E.

    2014-01-01

    Accurate cervical intra-epithelial neoplasia (CIN) lesion grading is needed for effective patient management. We applied computer-assisted scanning and analytic approaches to immuno-stained CIN lesion sections to more accurately delineate disease states and decipher cell proliferation impacts from HPV and smoking within individual epithelial layers. A patient cohort undergoing cervical screening was identified (n = 196) and biopsies of varying disease grades and with intact basement membranes and epithelial layers were obtained (n = 261). Specimens were sectioned, stained (Mib1), and scanned using a high-resolution imaging system. We achieved semi-automated delineation of proliferation status and epithelial cell layers using Otsu segmentation, manual image review, Voronoi tessellation, and immuno-staining. Data were interrogated against known status for HPV infection, smoking, and disease grade. We observed increased cell proliferation and decreased epithelial thickness with increased disease grade (when analyzing the epithelium at full thickness). Analysis within individual cell layers showed a ≥50% increase in cell proliferation for CIN2 vs. CIN1 lesions in higher epithelial layers (with minimal differences seen in basal/parabasal layers). Higher rates of proliferation for HPV-positive vs. -negative cases were seen in epithelial layers beyond the basal/parabasal layers in normal and CIN1 tissues. Comparing smokers vs. non-smokers, we observed increased cell proliferation in parabasal (low and high grade lesions) and basal layers (high grade only). In sum, we report CIN grade-specific differences in cell proliferation within individual epithelial layers. We also show HPV and smoking impacts on cell layer-specific proliferation. Our findings yield insight into CIN progression biology and demonstrate that rigorous, semi-automated imaging of histopathological specimens may be applied to improve disease grading accuracy. PMID:25210770

  10. Epithelial expression and chromosomal location of human TLE genes: Implications for notch signaling and neoplasia

    SciTech Connect

    Liu, Yanling; Dehni, Ghassan; Stifani, S.

    1996-01-01

    The TLE genes are the human homologues of Drosophila groucho, a member of the Notch signaling pathway. This pathway controls a number of different cell-fate choices in invertebrates and vertebrates. We are interested in investigating the functions of the TLE gene family during epithelial determination and carcinogenesis. We show that expression of individual TLE genes correlates with immature epithelial cells that are progressing toward their terminally differentiated state, suggesting a role during epithelial differentiation. In both normal tissues and conditions resulting from incorrect or incomplete maturation events, such as metaplastic and neoplastic transformations, TLE expression is elevated and coincides with Notch expression, implicating these molecules in the maintenance of the undifferentiated state in epithelial cells. We also show that TLE1 and TLE2 are organized in a tandem array at chromosomal location 19p13.3, while TLE3 maps to 15q22. 26 refs., 4 figs.

  11. HPV infection, anal intra-epithelial neoplasia (AIN) and anal cancer: current issues

    PubMed Central

    2012-01-01

    Background Human papillomavirus (HPV) is well known as the major etiological agent for ano-genital cancer. In contrast to cervical cancer, anal cancer is uncommon, but is increasing steadily in the community over the last few decades. However, it has undergone an exponential rise in the men who have sex with men (MSM) and HIV + groups. HIV + MSM in particular, have anal cancer incidences about three times that of the highest worldwide reported cervical cancer incidences. Discussion There has therefore traditionally been a lack of data from studies focused on heterosexual men and non-HIV + women. There is also less evidence reporting on the putative precursor lesion to anal cancer (AIN – anal intraepithelial neoplasia), when compared to cervical cancer and CIN (cervical intraepithelial neoplasia). This review summarises the available biological and epidemiological evidence for HPV in the anal site and the pathogenesis of AIN and anal cancer amongst traditionally non-high risk groups. Summary There is strong evidence to conclude that high-grade AIN is a precursor to anal cancer, and some data on the progression of AIN to invasive cancer. PMID:22958276

  12. VEGF elicits epithelial-mesenchymal transition (EMT) in prostate intraepithelial neoplasia (PIN)-like cells via an autocrine loop.

    PubMed

    Gonzalez-Moreno, Oscar; Lecanda, Jon; Green, Jeffrey E; Segura, Victor; Catena, Raul; Serrano, Diego; Calvo, Alfonso

    2010-02-15

    Vascular endothelial growth factor (VEGF) is overexpressed during the transition from prostate intraepithelial neoplasia (PIN) to invasive carcinoma. We have mimicked such a process in vitro using the PIN-like C3(1)/Tag-derived Pr-111 cell line, which expresses low levels of VEGF and exhibits very low tumorigenicity in vivo. Elevated expression of VEGF164 in Pr-111 cells led to a significant increase in tumorigenicity, invasiveness, proliferation rates and angiogenesis. Moreover, VEGF164 induced strong changes in cell morphology and cell transcriptome through an autocrine mechanism, with changes in TGF-beta1- and cytoskeleton-related pathways, among others. Further analysis of VEGF-overexpressing Pr-111 cells or following exogenous addition of recombinant VEGF shows acquisition of epithelial-mesenchymal transition (EMT) features, with an increased expression of mesenchymal markers, such as N-cadherin, Snail1, Snail2 (Slug) and vimentin, and a decrease in E-cadherin. Administration of VEGF led to changes in TGF-beta1 signaling, including reduction of Smad7 (TGF-beta inhibitory Smad), increase in TGF-betaR-II, and translocation of phospho-Smad3 to the nucleus. Our results suggest that increased expression of VEGF in malignant cells during the transition from PIN to invasive carcinoma leads to EMT through an autocrine loop, which would promote tumor cell invasion and motility. Therapeutic blockade of VEGF/TGF-beta1 in PIN lesions might impair not only tumor angiogenesis, but also the early dissemination of malignant cells outside the epithelial layer.

  13. Toll pathway modulates TNF-induced JNK-dependent cell death in Drosophila.

    PubMed

    Wu, Chenxi; Chen, Changyan; Dai, Jianli; Zhang, Fan; Chen, Yujun; Li, Wenzhe; Pastor-Pareja, José Carlos; Xue, Lei

    2015-07-01

    Signalling networks that control the life or death of a cell are of central interest in modern biology. While the defined roles of the c-Jun N-terminal kinase (JNK) pathway in regulating cell death have been well-established, additional factors that modulate JNK-mediated cell death have yet to be fully elucidated. To identify novel regulators of JNK-dependent cell death, we performed a dominant-modifier screen in Drosophila and found that the Toll pathway participates in JNK-mediated cell death. Loss of Toll signalling suppresses ectopically and physiologically activated JNK signalling-induced cell death. Our epistasis analysis suggests that the Toll pathway acts as a downstream modulator for JNK-dependent cell death. In addition, gain of JNK signalling results in Toll pathway activation, revealed by stimulated transcription of Drosomycin (Drs) and increased cytoplasm-to-nucleus translocation of Dorsal. Furthermore, the Spätzle (Spz) family ligands for the Toll receptor are transcriptionally upregulated by activated JNK signalling in a non-cell-autonomous manner, providing a molecular mechanism for JNK-induced Toll pathway activation. Finally, gain of Toll signalling exacerbates JNK-mediated cell death and promotes cell death independent of caspases. Thus, we have identified another important function for the evolutionarily conserved Toll pathway, in addition to its well-studied roles in embryonic dorso-ventral patterning and innate immunity.

  14. Optimal fluorescence excitation wavelengths for detection of squamous intra-epithelial neoplasia: results from an animal model

    NASA Astrophysics Data System (ADS)

    Coghlan, Lezlee; Utzinger, Urs; Drezek, Rebekah A.; Heintzelmann, Doug; Zuluaga, Andres F.; Brookner, Carrie; Richards-Kortum, Rebecca R.; Gimenez-Conti, Irma; Follen, Michele

    2000-12-01

    Using the hamster cheek pouch carcinogenesis model, we explore which fluorescence excitation wavelengths are useful for the detection of neoplasia. 42 hamsters were treated with DMBA to induce carcinogenesis, and 20 control animals were treated only with mineral oil. Fluorescence excitation emission matrices were measured from the cheek pouches of the hamsters weekly. Results showed increased fluorescence near 350-370 nm and 410 nm excitation and decreased fluorescence near 450-470 nm excitation with neoplasia. The optimal diagnostic excitation wavelengths identified using this model - 350-370 nm excitation and 400-450 nm excitation - are similar to those identified for detection of human oral cavity neoplasia.

  15. Proto-oncogenes and p53 protein expression in normal cervical stratified squamous epithelium and cervical intra-epithelial neoplasia.

    PubMed

    Ngan, H Y; Liu, S S; Yu, H; Liu, K L; Cheung, A N

    1999-10-01

    The aim of this study was to study the protein expression of six proto-oncogenes (epidermal growth factor receptor (EGFR), c-fms, c-myc, c-kit, c-erbB-2 and pan-ras) and one tumour suppressor gene (TP53), by immunohistochemical staining of normal cervical stratified squamous epithelium and cervical intra-epithelial neoplasia (CIN). Paraffin sections of 45 normal cervical specimens, 38 CIN grade one (CIN1), 37 CIN2 and 43 CIN3 were studied. An immunohistochemical (IHC) score was derived from the intensity of staining and the percentages of cells stained. In normal cervical specimens, a higher IHC score was found with EGFR and c-fms in superficial (S), intermediate (I) and parabasal (PB) cells compared with basal cells. In contrast, a higher IHC score was found with c-erbB-2 in basal cells in normal cervical specimens. Dysplastic cells in CIN had a higher IHC score with c-myc and c-erbB-2 than normal S/I and PB cells. Dysplastic cells had a higher score with EGFR than normal basal cells. However, a higher IHC score with EGFR and c-fms was found in normal S/I cells than dysplastic cells. These findings suggested that EGFR and c-fms were activated in more differentiated normal cells but were less active in less differentiated normal basal cells. However, EGFR was reactivated in dysplastic cells. Meanwhile, c-erbB-2 was activated in less differentiated normal basal cells and dysplastic cells, and was less active in differentiated normal cells. c-myc was activated in dysplastic cells. c-fms was more active in more differentiated normal cells and was not activated in less differentiated or dysplastic cells. c-kit, pan-ras and TP53 were not activated in normal nor dysplastic cervical cells. These results suggest EGFR, c-erbB-2 and c-myc may be important proto-oncogenes in CIN and that antibodies or anti-genes targeted against them may alter the progress of CIN to invasive cancer.

  16. In-Vivo Nonlinear Optical Microscopy (NLOM) of Epithelial-Connective Tissue Interface (ECTI) Reveals Quantitative Measures of Neoplasia in Hamster Oral Mucosa

    PubMed Central

    Pal, Rahul; Yang, Jinping; Ortiz, Daniel; Qiu, Suimin; Resto, Vicente; McCammon, Susan; Vargas, Gracie

    2015-01-01

    The epithelial-connective tissue interface (ECTI) plays an integral role in epithelial neoplasia, including oral squamous cell carcinoma (OSCC). This interface undergoes significant alterations due to hyperproliferating epithelium that supports the transformation of normal epithelium to precancers and cancer. We present a method based on nonlinear optical microscopy to directly assess the ECTI and quantify dysplastic alterations using a hamster model for oral carcinogenesis. Neoplastic and non-neoplastic normal mucosa were imaged in-vivo by both multiphoton autofluorescence microscopy (MPAM) and second harmonic generation microscopy (SHGM) to obtain cross-sectional reconstructions of the oral epithelium and lamina propria. Imaged sites were biopsied and processed for histopathological grading and measurement of ECTI parameters. An ECTI shape parameter was calculated based on deviation from the linear geometry (ΔLinearity) seen in normal mucosa was measured using MPAM-SHGM and histology. The ECTI was readily visible in MPAM-SHGM and quantitative shape analysis showed ECTI deformation in dysplasia but not in normal mucosa. ΔLinearity was significantly (p < 0.01) higher in dysplasia (0.41±0.24) than normal (0.11±0.04) as measured in MPAM-SHGM and results were confirmed in histology which showed similar trends in ΔLinearity. Increase in ΔLinearity was also statistically significant for different grades of dysplasia. In-vivo ΔLinearity measurement alone from microscopy discriminated dysplasia from normal tissue with 87.9% sensitivity and 97.6% specificity, while calculations from histology provided 96.4% sensitivity and 85.7% specificity. Among other quantifiable architectural changes, a progressive statistically significant increase in epithelial thickness was seen with increasing grade of dysplasia. MPAM-SHGM provides new noninvasive ways for direct characterization of ECTI which may be used in preclinical studies to investigate the role of this interface in

  17. IL-6 signaling by STAT3 participates in the change from hyperplasia to neoplasia in NRP-152 and NRP-154 rat prostatic epithelial cells

    PubMed Central

    Barton, Beverly E; Murphy, Thomas F; Adem, Patricia; Watson, Richard A; Irwin, Robert J; Huang, Hosea F

    2001-01-01

    Background STAT3 phosphorylation is associated with the neoplastic state in many types of cancer, including prostate cancer. We investigated the role of IL-6 signaling and phosphorylation of STAT3 in 2 rat prostatic epithelial lines. NRP-152 and NRP-154 cells were derived from the same rat prostate, yet the NRP-152 cells are not tumorigenic while the NRP-154 cells are tumorigenic. These lines are believed to represent 2 of the stages in the development of prostate cancer, hyperplasia and neoplasia. Differences in signaling pathways should play a role in the 2 phenotypes, hyperplastic and neoplastic. Methods We looked at the phosphorylation state of STAT3 by intracellular flow cytometry, using phospho-specific antibodies to STAT3. We used the same method to examine IL-6 production by the cell lines. We also measured apoptosis by binding of fluorescent annexin V to the cells. Results Although both cells lines made IL-6 constitutively, phosphorylated-STAT3 was present in untreated NRP-154 cells, but not in NRP-152 cells. Treatment with dexamethasone inhibited the IL-6 production of NRP-152 cells, but enhanced that of NRP-154 cells. Treatment with the JAK2 inhibitor AG490 induced apoptosis in NRP-152, but not NRP-154 cells. Conclusions We conclude from these experiments that STAT3 activity plays a role in the phenotype of NRP-154 cell, but not NRP-152 cells. The significance of alternative IL-6 signaling pathways in the different phenotypes of the 2 cell lines is discussed. PMID:11710966

  18. JNK-dependent Atg4 upregulation mediates asperphenamate derivative BBP-induced autophagy in MCF-7 cells

    SciTech Connect

    Li, Yanchun; Luo, Qiyu; Yuan, Lei; Miao, Caixia; Mu, Xiaoshuo; Xiao, Wei; Li, Jianchun; Sun, Tiemin; Ma, Enlong

    2012-08-15

    N-Benzoyl-O-(N′-(1-benzyloxycarbonyl-4-piperidiylcarbonyl) -D-phenylalanyl)-D-phenylalaninol (BBP), a novel synthesized asperphenamate derivative with the increased solubility, showed growth inhibitory effect on human breast carcinoma MCF-7 cells in a time- and concentration-dependent manner. The growth inhibitory effect of BBP was associated with induction of autophagy, which was demonstrated by the development of acidic vesicular organelles, cleavage of LC3 and upregulation of Atg4 in BBP-treated MCF-7 cells. Since the application of Atg4 siRNA totally blocked the cleavage of LC3, we demonstrated a central role of Atg4 in BBP-induced autophagy. The further studies showed that BBP increased the levels of reactive oxygen species (ROS), and pretreatment with NAC effectively blocked the accumulation of ROS, autophagy and growth inhibition triggered by BBP. Moreover, BBP induced the activation of JNK, and JNK inhibitor SP600125 reversed autophagy, the increase of Atg4 levels, conversion of LC3 and growth inhibition induced by BBP. Knockdown of JNK by siRNA efficiently inhibited ROS production and autophagy, but antioxidant NAC failed to block JNK activation induced by BBP, indicating that JNK activation may be a upstream signaling of ROS and should be a core component in BBP-induced autophagic signaling pathway. These results suggest that BBP produces its growth inhibitory effect through induction of the autophagic cell death in MCF-7 cells, which is modulated by a JNK-dependent Atg4 upregulation involving ROS production. -- Highlights: ► Asperphenamate derivative BBP with increased solubility was synthesized. ► BBP selectively inhibited the growth of human breast tumor cells. ► The growth inhibitory effect of BBP was associated with induction of autophagy. ► JNK-dependent Atg4 upregulation mediated BBP-induced autophagy.

  19. Oxidized lipids activate autophagy in a JNK-dependent manner by stimulating the endoplasmic reticulum stress response.

    PubMed

    Haberzettl, Petra; Hill, Bradford G

    2013-01-01

    Excessive production of unsaturated aldehydes from oxidized lipoproteins and membrane lipids is a characteristic feature of cardiovascular disease. Our previous studies show that unsaturated lipid peroxidation-derived aldehydes such as 4-hydroxy-trans-2-nonenal (HNE) promote autophagy in rat aortic smooth muscle cells (RASMC). In this study, we examined the mechanism by which HNE induces autophagy. Exposure of RASMC to HNE led to the modification of several proteins, most of which were identified by mass spectrometry and confocal microscopy to be localized to the endoplasmic reticulum (ER). HNE stimulated the phosphorylation of PKR-like ER kinase and eukaryotic initiation factor 2α and increased heme oxygenase-1 (HO-1) abundance. HNE treatment also increased LC3-II formation and the phosphorylation of JNK and p38. Pharmacological inhibition of JNK, but not p38, prevented HNE-induced HO-1 expression and LC3-II formation. Inhibition of JNK increased cell death in HNE-treated cells. Pretreatment with the chemical chaperone phenylbutryic acid prevented LC3-II formation as well as JNK phosphorylation and HO-1 induction. Taken together, these data suggest that autophagic responses triggered by unsaturated aldehydes could be attributed, in part, to ER stress, which stimulates autophagy by a JNK-dependent mechanism and promotes cell survival during oxidative stress.

  20. JNK-dependent Atg4 upregulation mediates asperphenamate derivative BBP-induced autophagy in MCF-7 cells.

    PubMed

    Li, Yanchun; Luo, Qiyu; Yuan, Lei; Miao, Caixia; Mu, Xiaoshuo; Xiao, Wei; Li, Jianchun; Sun, Tiemin; Ma, Enlong

    2012-08-15

    N-Benzoyl-O-(N'-(1-benzyloxycarbonyl-4-piperidiylcarbonyl)-D-phenylalanyl)-D-phenylalaninol (BBP), a novel synthesized asperphenamate derivative with the increased solubility, showed growth inhibitory effect on human breast carcinoma MCF-7 cells in a time- and concentration-dependent manner. The growth inhibitory effect of BBP was associated with induction of autophagy, which was demonstrated by the development of acidic vesicular organelles, cleavage of LC3 and upregulation of Atg4 in BBP-treated MCF-7 cells. Since the application of Atg4 siRNA totally blocked the cleavage of LC3, we demonstrated a central role of Atg4 in BBP-induced autophagy. The further studies showed that BBP increased the levels of reactive oxygen species (ROS), and pretreatment with NAC effectively blocked the accumulation of ROS, autophagy and growth inhibition triggered by BBP. Moreover, BBP induced the activation of JNK, and JNK inhibitor SP600125 reversed autophagy, the increase of Atg4 levels, conversion of LC3 and growth inhibition induced by BBP. Knockdown of JNK by siRNA efficiently inhibited ROS production and autophagy, but antioxidant NAC failed to block JNK activation induced by BBP, indicating that JNK activation may be a upstream signaling of ROS and should be a core component in BBP-induced autophagic signaling pathway. These results suggest that BBP produces its growth inhibitory effect through induction of the autophagic cell death in MCF-7 cells, which is modulated by a JNK-dependent Atg4 upregulation involving ROS production. PMID:22668848

  1. Epithelial neoplasia coincides with exacerbated injury and fibrotic response in the lungs of Gprc5a-knockout mice following silica exposure

    PubMed Central

    Zhong, Shuangshuang; Song, Hongyong; Sun, Beibei; Zhou, Binhua P.; Deng, Jiong; Han, Baohui

    2015-01-01

    Exposure to crystalline silica is suggested to increase the risk for a variety of lung diseases, including fibrosis and lung cancer. However, epidemiological evidences for the exposure-risk relationship are ambiguous and conflicting, and experimental study from a reliable animal model to explore the relationship is lacking. We reasoned that a mouse model that is sensitive to both lung injury and tumorigenesis would be appropriate to evaluate the exposure-risk relationship. Previously, we showed that, Gprc5a−/− mice are susceptible to both lung tumorigenesis and endotoxin-induced acute lung injury. In this study, we investigated the biological consequences in Gprc5a−/− mouse model following silica exposure. Intra-tracheal administration of fine silica particles in Gprc5a−/− mice resulted in more severe lung injury and pulmonary inflammation than in wild-type mice. Moreover, an enhanced fibrogenic response, including EMT-like characteristics, was induced in the lungs of Gprc5a−/− mice compared to those from wild-type ones. Importantly, increased hyperplasia or neoplasia coincided with silica-induced tissue injury and fibrogenic response in lungs from Gprc5a−/− mice. Consistently, expression of MMP9, TGFβ1 and EGFR was significantly increased in lungs from silica-treated Gprc5a−/− mice compared to those untreated or wild-type ones. These results suggest that, the process of tissue repair coincides with tissue damages; whereas persistent tissue damages leads to abnormal repair or neoplasia. Thus, silica-induced pulmonary inflammation and injury contribute to increased neoplasia development in lungs from Gprc5a−/− mouse model. PMID:26447616

  2. Neoplasia: The Second Decade

    PubMed Central

    Rehemtulla, Alnawaz

    2008-01-01

    This issue marks the end of the 10-year anniversary of Neoplasia where we have seen exciting growth in both number of submitted and published articles in Neoplasia. Neoplasia was first published in 1999. During the past 10 years, Neoplasia has dynamically adapted to the needs of the cancer research community as technologies have advanced. Neoplasia is currently providing access to articles through PubMed Central to continue to facilitate rapid broad-based dissemination of published findings to the scientific community through an Open Access model. This has in part helped Neoplasia to achieve an improved impact factor this past year, demonstrating that the manuscripts published by Neoplasia are of great interest to the overall cancer research community. This past year, Neoplasia received a record number of articles for review and has had a 21% increase in the number of published articles. PMID:19048110

  3. Multiple Endocrine Neoplasia Syndromes

    MedlinePlus

    ... or cancerous (malignant) tumors or grow excessively without forming tumors. Multiple endocrine neoplasia syndromes are caused by ... This Article Generic Name Select Brand Names corticotropin H.P. ACTHAR GEL epinephrine ADRENALIN Multiple Endocrine Neoplasia ...

  4. Activation of Wnt/β-catenin signaling in a subpopulation of murine prostate luminal epithelial cells induces high grade prostate intraepithelial neoplasia

    PubMed Central

    Valkenburg, Kenneth C.; Yu, Xiuping; De Marzo, Angelo M.; Spiering, Tyler; Matusik, Robert J.; Williams, Bart O.

    2014-01-01

    Background Wnt/β-catenin signaling is important for prostate development and cancer in humans. Activation of this pathway in differentiated luminal cells of mice induces high-grade prostate intraepithelial neoplasia (HGPIN). Though the cell of origin of prostate cancer has yet to be conclusively identified, a castration-resistant Nkx3.1-expressing cell (CARN) may act as a cell of origin for prostate cancer. Methods To activate Wnt/β-catenin signaling in CARNs, we crossed mice carrying tamoxifen-inducible Nkx3.1-driven Cre to mice containing loxP sites in order to either conditionally knock out adenomatous polyposis coli (Apc) or constitutively activate β-catenin directly. We then castrated and hormonally regenerated these mice to target the CARN population. Results Loss of Apc in hormonally normal mice induced HGPIN; however, after one or more rounds of castration and hormonal regeneration, Apc-null CARNs disappeared. Alternatively, when β-catenin was constitutively activated under the same conditions, HGPIN was apparent. Conclusion Activation of Wnt/β-catenin signaling via Apc deletion is sufficient to produce HGPIN in hormonally normal mice. Loss of Apc may destabilize the CARN population under regeneration conditions. When β-catenin is constitutively activated, HGPIN occurs in hormonally regenerated mice. A second genetic hit is likely required to cause progression to carcinoma and metastasis. PMID:25175604

  5. Comparison of a physical model and principal component analysis for the diagnosis of epithelial neoplasias in vivo using diffuse reflectance spectroscopy

    NASA Astrophysics Data System (ADS)

    Skala, Melissa C.; Palmer, Gregory M.; Vrotsos, Kristin M.; Gendron-Fitzpatrick, Annette; Ramanujam, Nirmala

    2007-06-01

    We explored the use of diffuse reflectance spectroscopy in the ultraviolet-visible (UV-VIS) spectrum for the diagnosis of epithelial pre-cancers and cancers in vivo. A physical model (Monte Carlo inverse model) and an empirical model [principal component analysis, (PCA)] based approach were compared for extracting diagnostic features from diffuse reflectance spectra measured in vivo from the dimethylbenz[α]anthracene-treated hamster cheek pouch model of oral carcinogenesis. These diagnostic features were input into a support vector machine algorithm to classify each tissue sample as normal (n=10) or neoplastic (dysplasia to carcinoma, n=10) and cross-validated using a leave one out method. There was a statistically significant decrease in the absorption and reduced scattering coefficient at 460 nm in neoplastic compared to normal tissues, and these two features provided 90% classification accuracy. The first two principal components extracted from PCA provided a classification accuracy of 95%. The first principal component was highly correlated with the wavelength-averaged reduced scattering coefficient. Although both methods show similar classification accuracy, the physical model provides insight into the physiological and structural features that discriminate between normal and neoplastic tissues and does not require a priori, a representative set of spectral data from which to derive the principal components.

  6. Cervical Neoplasia Probe Control

    1997-01-24

    This software, which consists of a main executive and several subroutines, performs control of the optics, image acquisition, and Digital Signal Processing (DSP) of this image, of an optical based medical instrument that performs fluoresence detection of precancerous lesions (neoplasia) of the human cervix. The hardware portion of this medical instrument is known by the same name Cervical Neoplasia Probe (CNP)

  7. Xenopus Pkdcc1 and Pkdcc2 Are Two New Tyrosine Kinases Involved in the Regulation of JNK Dependent Wnt/PCP Signaling Pathway

    PubMed Central

    Vitorino, Marta; Silva, Ana Cristina; Inácio, José Manuel; Ramalho, José Silva; Gur, Michal; Fainsod, Abraham; Steinbeisser, Herbert; Belo, José António

    2015-01-01

    Protein Kinase Domain Containing, Cytoplasmic (PKDCC) is a protein kinase which has been implicated in longitudinal bone growth through regulation of chondrocytes formation. Nevertheless, the mechanism by which this occurs remains unknown. Here, we identified two new members of the PKDCC family, Pkdcc1 and Pkdcc2 from Xenopus laevis. Interestingly, our knockdown experiments revealed that these two proteins are both involved on blastopore and neural tube closure during gastrula and neurula stages, respectively. In vertebrates, tissue polarity and cell movement observed during gastrulation and neural tube closure are controlled by Wnt/Planar Cell Polarity (PCP) molecular pathway. Our results showed that Pkdcc1 and Pkdcc2 promote the recruitment of Dvl to the plasma membrane. But surprisingly, they revealed different roles in the induction of a luciferase reporter under the control of Atf2 promoter. While Pkdcc1 induces Atf2 expression, Pkdcc2 does not, and furthermore inhibits its normal induction by Wnt11 and Wnt5a. Altogether our data show, for the first time, that members of the PKDCC family are involved in the regulation of JNK dependent Wnt/PCP signaling pathway. PMID:26270962

  8. Immunohistochemistry of Pancreatic Neoplasia

    PubMed Central

    Kaur, Sukhwinder; Shimizu, Tomohiro; Baine, Michael J.; Kumar, Sushil; Batra, Surinder K.

    2013-01-01

    Immunohistochemistry (IHC) is a valuable tool to visualize the distribution and localization of specific cellular components within morphologically preserved tissue sections or cell preparations. It combines the histologic morphology of tissues for detecting the actual antigen distribution, specificity of antibody–antigen interaction for optimal detection, and sensitivity of immunochemical methods for assessing the amount of antigen in tissues. It is routinely used clinically to diagnose type (benign or malignant), stage, and grade of cancer using specific tumor markers. The application of IHC ranges from disease diagnosis and prognosis to drug development and analysis of the pathobiological roles of various molecular players during disease development. Due to better availability of highly specific antibodies and optimal methodologies for performing immunohistochemical studies, IHC is being used at an expanding rate to understand pancreatic tumor biology as well as to study the fate of various molecular markers during the initiation, progression, and metastasis of pancreatic neoplasia. Herein, we describe the detailed protocol for IHC analyses of pancreatic intraepithelial neoplasia in tissues and fine needle aspirates from both human and mouse samples. PMID:23359148

  9. Quantitative proteomics investigation of pancreatic intraepithelial neoplasia

    PubMed Central

    Pan, Sheng; Chen, Ru; Reimel, Beth Ann; Crispin, David A.; Mirzaei, Hamid; Cooke, Kelly; Coleman, Joshua F.; Lane, Zhaoli; Bronner, Mary P.; Goodlett, David R.; McIntosh, Martin; Traverso, William; Aebersold, Ruedi; Brentnall, Teresa A.

    2009-01-01

    Patients with pancreatic cancer are usually diagnosed at late stages, when the disease is incurable. Pancreatic intraepithelial neoplasia (PanIN) 3, is believed to be the immediate precursor lesion of pancreatic adenocarcinoma, and would be an ideal stage to diagnose patients, when intervention and cure are possible and patients are curable. In this study, we used quantitative proteomics to identify dysregulated proteins in PanIN 3 lesions. Altogether, over 200 dysregulated proteins were identified in the PanIN 3 tissues, with a minimum of a 1.75 fold change compared to the proteins in normal pancreas. These dysregulated PanIN 3 proteins play roles in cell motility, the inflammatory response, the blood clotting cascade, the cell cycle and its regulation, and protein degradation. Further network analysis of the proteins identified c-MYC as an important regulatory protein in PanIN 3 lesions. Finally, three of the overexpressed proteins, laminin beta-1, galectin-1, and actinin-4 were validated by IHC analysis. All three of these proteins were overexpressed in the stroma or ductal epithelial cells of advanced PanIN lesions, as well as in pancreatic cancer tissue. Our findings suggest that these three proteins may be useful as biomarkers for advanced PanIN and pancreatic cancer if further validated. The dysregulated proteins identified in this study may assist in the selection of candidates for future development of biomarkers for detecting early and curable pancreatic neoplasia. PMID:19373808

  10. Pathophysiology of ocular surface squamous neoplasia

    PubMed Central

    Gichuhi, Stephen; Ohnuma, Shin-ichi; Sagoo, Mandeep S.; Burton, Matthew J.

    2014-01-01

    The incidence of ocular surface squamous neoplasia (OSSN) is strongly associated with solar ultraviolet (UV) radiation, HIV and human papilloma virus (HPV). Africa has the highest incidence rates in the world. Most lesions occur at the limbus within the interpalpebral fissure particularly the nasal sector. The nasal limbus receives the highest intensity of sunlight. Limbal epithelial crypts are concentrated nasally and contain niches of limbal epithelial stem cells in the basal layer. It is possible that these are the progenitor cells in OSSN. OSSN arises in the basal epithelial cells spreading towards the surface which resembles the movement of corneo-limbal stem cell progeny before it later invades through the basement membrane below. UV radiation damages DNA producing pyrimidine dimers in the DNA chain. Specific CC → TT base pair dimer transformations of the p53 tumour-suppressor gene occur in OSSN allowing cells with damaged DNA past the G1-S cell cycle checkpoint. UV radiation also causes local and systemic photoimmunosuppression and reactivates latent viruses such as HPV. The E7 proteins of HPV promote proliferation of infected epithelial cells via the retinoblastoma gene while E6 proteins prevent the p53 tumour suppressor gene from effecting cell-cycle arrest of DNA-damaged and infected cells. Immunosuppression from UV radiation, HIV and vitamin A deficiency impairs tumour immune surveillance allowing survival of aberrant cells. Tumour growth and metastases are enhanced by; telomerase reactivation which increases the number of cell divisions a cell can undergo; vascular endothelial growth factor for angiogenesis and matrix metalloproteinases (MMPs) that destroy the intercellular matrix between cells. Despite these potential triggers, the disease is usually unilateral. It is unclear how HPV reaches the conjunctiva. PMID:25447808

  11. Neoplasia: An Anniversary of Progress

    PubMed Central

    Rehemtulla, Alnawaz

    2007-01-01

    This issue marks the 10th year anniversary of Neoplasia where we have seen exciting growth on the impact that Neoplasia has had on cancer research worldwide. Neoplasia was founded in 1999 at which time manuscripts were accepted through e-mail. In 2000, Neoplasia became the first journal to offer web-based online manuscript submission and peer-review using a custom-designed application JournalSoft. Now, the use of web-based manuscript processing has become an industry standard as it provides authors with a rapid and useful dialog exchange for improving the quality of the science and the overall speed of the review process. Moreover, during the past 10 years, the Internet has experienced a massive growth of a complex global grid of now over an estimated 1.2 billion Internet users which have resulted in a major shift in the medium of scientific communication for scholarly publishing. Neoplasia continues to evolve with the technology and has implemented a rapid time-to-publication schedule to continue dissemination of published cancer research findings quickly to the scientific community.

  12. Radiogenic neoplasia in thyroid and mammary clonogens

    SciTech Connect

    Clifton, K.H.

    1991-05-31

    We have developed rat thyroid and mammary clonogen transplantation systems for the study of radiogenic cancer induction at the target cell level in vivo. The epithelial cell populations of both glands contain small subpopulations of cells which are capable of giving rise to monoclonal glandular structures when transplanted and stimulated with appropriate hormones. During the end of the last grant year and the first half of the current grant year, we have completed analyses and summarized for publication: investigations on the relationship between grafted thyroid cell number and the rapidity and degree of reestablishment of the thyroid-hypothalamicpituitary axis in thyroidectomized rats maintained on a normal diet or an iodine deficient diet; studies of the persistence of, and the differentiation potential and functional characteristics of, the TSH- (thyrotropin-) responsive sub-population of clonogens during goitrogenesis, the plateau-phase of goiter growth, and goiter involution; studies of changes in the size of the clonogen sub-population during goitrogenesis, goiter involution and the response to goitrogen rechallenge; and the results of the large carcinogenesis experiment on the nature of the grafted thyroid cell number-dependent suppression of promotion/progression to neoplasia in grafts of radiation-initiated thyroid cells. We are testing new techniques for the culture, cytofluorescent analysis and characterization mammary epithelial cells and of clonogens in a parallel project, and plan to apply similar technology to the thyroid epithelial cells and clonogen population. Data from these studies will be used in the design of future carcinogenesis experiments on neoplastic initiation by high and low LET radiations and on cells interactions during the neoplastic process.

  13. Animal models of pituitary neoplasia

    PubMed Central

    Lines, K.E.; Stevenson, M.; Thakker, R.V.

    2016-01-01

    Pituitary neoplasias can occur as part of a complex inherited disorder, or more commonly as sporadic (non-familial) disease. Studies of the molecular and genetic mechanisms causing such pituitary tumours have identified dysregulation of >35 genes, with many revealed by studies in mice, rats and zebrafish. Strategies used to generate these animal models have included gene knockout, gene knockin and transgenic over-expression, as well as chemical mutagenesis and drug induction. These animal models provide an important resource for investigation of tissue-specific tumourigenic mechanisms, and evaluations of novel therapies, illustrated by studies into multiple endocrine neoplasia type 1 (MEN1), a hereditary syndrome in which ∼30% of patients develop pituitary adenomas. This review describes animal models of pituitary neoplasia that have been generated, together with some recent advances in gene editing technologies, and an illustration of the use of the Men1 mouse as a pre clinical model for evaluating novel therapies. PMID:26320859

  14. Intrathoracic neoplasia: Epidemiology and etiology

    SciTech Connect

    Weller, R.E.

    1992-05-01

    Neoplasms of the thorax encompass those derived from the thoracic wall, trachea, mediastinum, lungs and pleura. They represent a wide variety of lesions including benign and malignant tumors arising from many tissues. The large surface area, 60 to 90 m{sup 2} in man, represented by the respiratory epithelium and associated thoracic structures are ideal targets for carcinogens carried by inspired air. The topic of discussion in this report is the epidemiology, etiology, and mechanisms of spontaneous intrathoracic neoplasia in animals and man. Much of what we know or suspect about thoracic neoplasia in animals has been extrapolated from experimentally-induced neoplasms.

  15. The contribution of heavy metals in cigarette smoke condensate to malignant transformation of breast epithelial cells and in vivo initiation of neoplasia through induction of a PI3K–AKT–NFκB cascade

    SciTech Connect

    Mohapatra, Purusottam; Preet, Ranjan; Das, Dipon; Satapathy, Shakti Ranjan; Siddharth, Sumit; Choudhuri, Tathagata; Wyatt, Michael D.; Kundu, Chanakya Nath

    2014-01-01

    Cigarette smoking is a crucial factor in the development and progression of multiple cancers including breast. Here, we report that repeated exposure to a fixed, low dose of cigarette smoke condensate (CSC) prepared from Indian cigarettes is capable of transforming normal breast epithelial cells, MCF-10A, and delineate the biochemical basis for cellular transformation. CSC transformed cells (MCF-10A-Tr) were capable of anchorage-independent growth, and their anchorage dependent growth and colony forming ability were higher compared to the non-transformed MCF-10A cells. Increased expression of biomarkers representative of oncogenic transformation (NRP-1, Nectin-4), and anti-apoptotic markers (PI3K, AKT, NFκB) were also noted in the MCF-10A-Tr cells. Short tandem repeat (STR) profiling of MCF-10A and MCF-10A-Tr cells revealed that transformed cells acquired allelic variation during transformation, and had become genetically distinct. MCF-10A-Tr cells formed solid tumors when implanted into the mammary fat pads of Balb/c mice. Data revealed that CSC contained approximately 1.011 μg Cd per cigarette equivalent, and Cd (0.0003 μg Cd/1 × 10{sup 7} cells) was also detected in the lysates from MCF-10A cells treated with 25 μg/mL CSC. In similar manner to CSC, CdCl{sub 2} treatment in MCF-10A cells caused anchorage independent colony growth, higher expression of oncogenic proteins and increased PI3K–AKT–NFκB protein expression. An increase in the expression of PI3K–AKT–NFκB was also noted in the mice xenografts. Interestingly, it was noted that CSC and CdCl{sub 2} treatment in MCF-10A cells increased ROS. Collectively, results suggest that heavy metals present in cigarettes of Indian origin may substantially contribute to tumorigenesis by inducing intercellular ROS accumulation and increased expression of PI3K, AKT and NFκB proteins. - Highlights: • Repeated exposure of CSC causes malignant transformation in MCF-10A. • MCF-10A-Tr cells showed a distinct

  16. Canine histiocytic neoplasia: An overview

    PubMed Central

    Fulmer, Amanda K.; Mauldin, Glenna E.

    2007-01-01

    Canine histiocytic neoplasms include cutaneous histiocytoma, as well as localized and disseminated histiocytic sarcoma. These tumors have variable biologic behavior, although the malignant disorders often have a poor prognosis. Immunohistochemistry plays an essential role in differentiating histiocytic tumors from other neoplasias that may have similar histological appearances. This allows a definitive diagnosis to be established and provides a more accurate prediction of prognosis. This article reviews the biologic behavior, diagnosis, and treatment of histiocytic tumors in the dog. PMID:17987966

  17. Marine mammal neoplasia: a review.

    PubMed

    Newman, S J; Smith, S A

    2006-11-01

    A review of the published literature indicates that marine mammal neoplasia includes the types and distributions of tumors seen in domestic species. A routine collection of samples from marine mammal species is hampered, and, hence, the literature is principally composed of reports from early whaling expeditions, captive zoo mammals, and epizootics that affect larger numbers of animals from a specific geographic location. The latter instances are most important, because many of these long-lived, free-ranging marine mammals may act as environmental sentinels for the health of the oceans. Examination of large numbers of mortalities reveals incidental proliferative and neoplastic conditions and, less commonly, identifies specific malignant cancers that can alter population dynamics. The best example of these is the presumptive herpesvirus-associated metastatic genital carcinomas found in California sea lions. Studies of tissues from St. Lawrence estuary beluga whales have demonstrated a high incidence of neoplasia and produced evidence that environmental contamination with high levels of polychlorinated biphenols and dichlorophenyl trichloroethane might be the cause. In addition, viruses are suspected to be the cause of gastric papillomas in belugas and cutaneous papillomas in Florida manatees and harbor porpoises. While experimental laboratory procedures can further elucidate mechanisms of neoplasia, continued pathologic examination of marine mammals will also be necessary to follow trends in wild populations. PMID:17099143

  18. New concepts in neoplasia as applied to diagnostic pathology

    SciTech Connect

    Fenoglio-Preiser, C.M.; Weinstein, R.S.; Kaufman, N.

    1986-01-01

    This book contains 13 selections. Some of the titles are: Cellular Aspects of Neoplasia; Oncogenes and Cancer; Chromosome and Oncogene Rearrangements in Leukemia and Lymphoma; Ionizing Radiation and Neoplasia; and Papillomaviruses and Neoplasia in Man.

  19. Radiogenic neoplasia in thyroid and mammary clonogens

    SciTech Connect

    Clifton, K.H.

    1992-05-20

    We have developed rat thyroid and mammary clonogen transplantation systems for the study of radiogenic cancer induction at the target cell level in vivo. The epithelial cell populations of both glands contain small subpopulations of cells which are capable of giving rise to monoclonal glandular structures when transplanted and stimulated with appropriate hormones. Previous results indicated that these clonogens are the precursor cells of radiogenic cancer, and that initiation, is common event at the clonegenic cell level. Detailed information on the physiologic control of clonogen proliferation, differentiation, and total numbers is thus essential to an understanding of the carcinogenic process. We report here studies on investigations on the relationships between grafted thyroid cell number and the rapidity and degree of reestablishment of the thyroid-hypothalamus-pituitary feedback axis in thyroidectomized rats maintained on a normal diet or an iodine deficient diet; studies of the persistence of, and the differentiation potential and functional characteristics of, the TSH-(thyrotropin-) responsive sub- population of clonogens during goitrogenesis, the plateau-phase of goiter growth, and goiter involution; studies of changes in the size of the clonogen sub-population during goitrogenesis, goiter involution and the response to goitrogen rechallenge; and a large carcinogenesis experiment on the nature of the grafted thyroid cell number-dependent suppression of promotion/progression to neoplasia in grafts of radiation-initiated thyroid cells. Data from these studies will be used in the design of future carcinogenesis experiments on neoplastic initiation by high and low LET radiations and on cell interactions during the neoplastic process.

  20. Multiple endocrine neoplasia type 2.

    PubMed

    Lodish, Maya

    2013-01-01

    Multiple endocrine neoplasia type 2 (MEN2) is an autosomal-dominant cancer syndrome characterized by variable penetrance of medullary thyroid carcinoma(MTC), pheochromocytoma (PHEO), and primary hyperparathyroidism (PHPT). MEN2 consists of two clinical subtypes, MEN2A and MEN2B. Familial medullary thyroid cancer is now viewed as a phenotypic variant of MEN2A with decreased penetrance for PHEO and PHPT rather than a distinct entity. All subtypes are caused by gain-of-function mutations of the RET proto-oncogene. Genotype-phenotype correlations exist that help predict the presence of other associated endocrine neoplasms as well as the timing of thyroid cancer development. Recognition of the clinical entity in individuals and families at risk of harboring a germline RET mutation is crucial for the management and prevention of associated malignancies. Recent guidelines released by the American Thyroid Association regarding the management of MTC will be summarized in this chapter.

  1. Update on Pancreatic Intraepithelial Neoplasia

    PubMed Central

    Hruban, Ralph H; Maitra, Anirban; Goggins, Michael

    2008-01-01

    Pancreatic intraepithelial neoplasia (PanIN) is a histologically well-defined precursor to invasive ductal adenocarcinoma of the pancreas. PanINs are remarkably common lesions, particularly in the elderly population. Molecular studies have helped establish the progression of PanIN to invasive cancer, and recently genetically engineered mouse models have been generated that recapitulate the entire spectrum of lesions from precursor to invasive pancreatic cancer. Some PanIN lesions produce lobulocentric atrophy of the pancreatic parenchyma, and, when multifocal, this lobulocentric atrophy may be detectable using currently available imaging techniques such as endoscopic ultrasound. The association of acinar-ductal metaplasia with PanIN lesions has led some to hypothesize that PanINs develop from acinar cells that undergo acinar-ductal metaplasia. PMID:18787611

  2. Fluorescence detection of esophageal neoplasia

    NASA Astrophysics Data System (ADS)

    Borisova, E.; Vladimirov, B.; Avramov, L.

    2008-06-01

    White-light endoscopy is well-established and wide used modality. However, despite the many technological advances that have been occurred, conventional endoscopy is suboptimal and usually detects advanced stage lesions. The limitations of standard endoscopy initiate development of spectroscopic techniques, additional to standard endoscopic equipment. One of the most sensitive approaches is fluorescence spectroscopy of gastrointestinal mucosa for neoplasia detection. In the recent study delta-aminolevulinic acid/Protoporphyrin IX (5-ALA/PpIX) is used as fluorescent marker for dysplasia and tumor detection in esophagus. The 5-ALA is administered per os six hours before measurements at dose 20 mg/kg weight. Excitation source has max of emission at 405 nm and light is delivered by the standard light guide of the endoscopic equipment. Through endoscopic instrumental channel a fiber is applied to return information about fluorescence to microspectrometer. Spectral features observed during endoscopic investigations could be distinct as the next regions: 450-630 nm region, where tissue autofluorescence is observed; 630-710 nm region, where fluorescence of PpIX is clearly pronounced; 530-580 nm region, where minima in the autofluorescence signal are observed, related to reabsorption of blood. The lack of fluorescence peaks in the red spectral area for normal mucosa is an indication for selective accumulation of 5-ALA/PpIX only in abnormal sites Very good correlation between fluorescence signals and histology examination of the lesions investigated is achieved.

  3. Fractal Analysis of Cervical Intraepithelial Neoplasia

    PubMed Central

    Fabrizii, Markus; Moinfar, Farid; Jelinek, Herbert F.; Karperien, Audrey; Ahammer, Helmut

    2014-01-01

    Introduction Cervical intraepithelial neoplasias (CIN) represent precursor lesions of cervical cancer. These neoplastic lesions are traditionally subdivided into three categories CIN 1, CIN 2, and CIN 3, using microscopical criteria. The relation between grades of cervical intraepithelial neoplasia (CIN) and its fractal dimension was investigated to establish a basis for an objective diagnosis using the method proposed. Methods Classical evaluation of the tissue samples was performed by an experienced gynecologic pathologist. Tissue samples were scanned and saved as digital images using Aperio scanner and software. After image segmentation the box counting method as well as multifractal methods were applied to determine the relation between fractal dimension and grades of CIN. A total of 46 images were used to compare the pathologist's neoplasia grades with the predicted groups obtained by fractal methods. Results Significant or highly significant differences between all grades of CIN could be found. The confusion matrix, comparing between pathologist's grading and predicted group by fractal methods showed a match of 87.1%. Multifractal spectra were able to differentiate between normal epithelium and low grade as well as high grade neoplasia. Conclusion Fractal dimension can be considered to be an objective parameter to grade cervical intraepithelial neoplasia. PMID:25302712

  4. Quantitative evaluation of in vivo vital-dye fluorescence endoscopic imaging for the detection of Barrett's-associated neoplasia

    NASA Astrophysics Data System (ADS)

    Thekkek, Nadhi; Lee, Michelle H.; Polydorides, Alexandros D.; Rosen, Daniel G.; Anandasabapathy, Sharmila; Richards-Kortum, Rebecca

    2015-05-01

    Current imaging tools are associated with inconsistent sensitivity and specificity for detection of Barrett's-associated neoplasia. Optical imaging has shown promise in improving the classification of neoplasia in vivo. The goal of this pilot study was to evaluate whether in vivo vital dye fluorescence imaging (VFI) has the potential to improve the accuracy of early-detection of Barrett's-associated neoplasia. In vivo endoscopic VFI images were collected from 65 sites in 14 patients with confirmed Barrett's esophagus (BE), dysplasia, or esophageal adenocarcinoma using a modular video endoscope and a high-resolution microendoscope (HRME). Qualitative image features were compared to histology; VFI and HRME images show changes in glandular structure associated with neoplastic progression. Quantitative image features in VFI images were identified for objective image classification of metaplasia and neoplasia, and a diagnostic algorithm was developed using leave-one-out cross validation. Three image features extracted from VFI images were used to classify tissue as neoplastic or not with a sensitivity of 87.8% and a specificity of 77.6% (AUC=0.878). A multimodal approach incorporating VFI and HRME imaging can delineate epithelial changes present in Barrett's-associated neoplasia. Quantitative analysis of VFI images may provide a means for objective interpretation of BE during surveillance.

  5. [VULVAR INTRAEPITHELIAL NEOPLASIA--TERMINOLOGY, SYMPTOMS AND TREATMENT].

    PubMed

    Ganovska, A; Kovachev, S

    2015-01-01

    The term vulvar intraepithelial neoplasia (VIN) was introduced for first time in 1986 year from the International Society for the Study of Vulvar Disease (ISSVD). With this term are denoted precancer vulvar conditions. According to a classification dated 1986 depending on the degree of affection of multilayered squamous epithelial vulvar precancerous lesion are subdivided into three groups: VINI, VIN2 and VIN3. Subsequently VIN1 is determinate as a lesion which there isn't oncogenic potential. These types of changes often are result from irritation or viral infection which leads to benign condylomata acuminate. Compare to lesions with VIN require histological signs for high grade intraepithelial neoplasia as nuclear pleomorphism, increased mitotic activity, atypical mitotic activity and disordered architecture of squamous cells epithelium. These fundamental morphologic characterizations lead to revision and subsequent change of the current classification. In 2004 ISSVD changed the classification. It included lesions like VIN2 and VIN3, but they are subdivided in two groups: the usual type VIN and the differentiated VIN. They have different etiology, morphology, oncogenic potential and prognosis. The usual type VIN is associated with infection of high risk types of human papilloma virus and is a more frequently met form of VIN. A very good prognosis is characteristic for it. The differentiated VIN is met in postmenopausal women of about 70 with frequency of about 2-5%. It originated from vulvar dermatosis like lichen scierosus and there is a high oncogenic potential and worse prognosis. The treatment of VIN may be surgical and by medicines. The frequency of recurrences after treatment is 30-50% which required frequently follows up. The aim of this literature review is to introduce present terminological classification of VIN, as well as basic clinical, diagnostically and curative methods in treat of the both types of this precancerous.

  6. Neither Neoplasia Nor Tuberculosis, but Francisella

    PubMed Central

    Mambie, Adeline; Wallet, Frédéric; Scherman, Laurine; Armand, Sylvie; Vervelle, Christine; Faure, Karine; Guery, Benoit; Titécat, Marie; Loïez, Caroline

    2016-01-01

    Tularaemia is an emerging anthropozoonosis transmitted by contact with infected animals and through arthropod bites, inhalation, or ingestion. We describe a pulmonary nodule suggesting cancer in a 70-year-old man. Histological analysis excluded neoplasia, and bacteriological culture excluded tuberculosis. Serological testing and PCR Francisella were positive for this hunter patient, then treated by ciprofloxacin with a favourable outcome. PMID:27419157

  7. High-Grade Prostatic Intraepithelial Neoplasia

    PubMed Central

    Bostwick, David G; Liu, Lina; Brawer, Michael K; Qian, Junqi

    2004-01-01

    High-grade prostatic intraepithelial neoplasia is considered the most likely precursor of prostatic carcinoma. The only method of detection is biopsy; prostatic intraepithelial neoplasia (PIN) does not significantly elevate serum prostate-specific antigen concentration and cannot be detected by ultra-sonography. The incidence of PIN in prostate biopsies averages 9% (range, 4%–16%), representing 115,000 new cases of PIN diagnosed each year in United States. PIN has a high predictive value as a marker for adenocarcinoma, and its identification warrants repeated biopsy for concurrent or subsequent invasive carcinoma. Carcinoma will develop in most patients with PIN within 10 years. PIN is associated with progressive abnormalities of phenotype and genotype that are intermediate between normal prostatic epithelium and cancer, indicating impairment of cell differentiation and regulatory control with advancing stages of prostatic carcinogenesis. Androgen deprivation therapy decreases the prevalence and extent of PIN, suggesting that this form of treatment may play a role in chemoprevention. PMID:16985598

  8. Common multigenic activation in different human neoplasias.

    PubMed Central

    Hanania, N; Shaool, D; Harel, J; Wiels, J; Tursz, T

    1983-01-01

    It was previously shown that a common multigenic component, designated as tumor-specific DNA (tsDNA), was transcriptionally active in human lymphoid neoplasias and only slightly active, if at all, in normal lymphoid cells, including the Priess cell line immortalized by Epstein-Barr virus. In the Burkitt lymphoma-derived Raji cell line, tsDNA corresponded to 2500-3000 distinct transcription units, arbitrarily defined as encoding mRNA chains of 1000 kds each. In the present study, radioactive Raji cell tsDNA was isolated by a recycling procedure which eliminates transcribed DNA sequences common to both the Raji cell and the Priess cell, and was used as a probe for homologous transcripts. The major part of this probe could be hybridized to RNAs from all the human neoplasias studied: cultured cell lines derived from leukemias, malignant lymphomas or sarcomas, leukemic cells or solid tumors (sarcomas and carcinomas) recovered from patients. In contrast, only a minor portion of Raji cell tsDNA could be hybridized to RNAs from non-malignant cells, normal human lymphoid cells or fibroblasts grown in culture, fetal and chorioplacental tissues. It is concluded that a common multigenic set is activated in a wide variety of, and perhaps in all, human neoplasias. PMID:6315395

  9. Endoscopic Treatment of Early Barrett's Neoplasia: Expanding Indications, New Challenges.

    PubMed

    Pech, Oliver

    2016-01-01

    Endoscopic therapy of early Barrett's neoplasia is nowadays the treatment of choice and recommended over surgery in most current guidelines. Recent data suggest radiofrequency ablation of low-grade intraepithelial neoplasia when confirmed by an expert pathologist. Endoscopic therapy of high-grade intraepithelial neoplasia and mucosal Barrett's adenocarcinoma consists of two steps: first endoscopic resection of all visible lesions, and second ablation of the remaining flat Barrett's mucosa to reduce the rate of recurrences and metachronous neoplasia. The preferred ablation method is radiofrequency ablation. In case of Barrett's adenocarcinoma with incipient submucosal invasion, endoscopic treatment can be considered curative when there are no further risk factors present. PMID:27573769

  10. Aetiology, pathogenesis, and pathology of cervical neoplasia.

    PubMed Central

    Arends, M J; Buckley, C H; Wells, M

    1998-01-01

    Early epidemiological studies of cervical neoplasia suggested a causal relation with sexual activity and human papillomaviruses (HPVs) have emerged as prime suspects as venerally transmitted carcinogens. HPVs fall into two broad camps: low risk types, associated with cervical condylomas and CIN 1; and high risk types (mostly 16 and 18), found in 50-80% of CIN 2 and CIN 3 lesions, and 90% of cancers. This association with cancer is very strong, with odds ratios of > 15 (often much higher) in case-control studies that are methodologically sound. An infrequently detected third group of intermediate risk type HPVs is associated with all grades of CIN and occasionally with cancers. HPVs have also been detected in a wide range of asymptomatic controls, indicating that other events are required for development of neoplasia such as viral persistence and/or altered expression of viral genes, often following integration of the viral genome. This leaves the two major viral oncogenes, E6 and E7, directly coupled to viral enhancers and promoters, allowing their continued expression after integration. High risk HPV E7 proteins bind and inactivate the Rb protein, whereas E6 proteins bind p53 and direct its rapid degradation. A range of putative cofactors has been implicated in progression: HLA type, immunosuppression, sex steroid hormones, and smoking; most of these cofactors appear to influence progression to CIN 3. The natural history includes progression to CIN 3 in 10% of CIN 1 and 20% of CIN 2 cases, whereas at least 12% of CIN 3 cases progress to invasive carcinoma. Cervical glandular intraepithelial neoplasia (CGIN) often coexists with squamous CIN, and the premalignant potential of high grade CGIN is not in doubt, but the natural history of low grade CGIN remains uncertain. A high proportion of CGIN lesions and adenocarcinomas are HPV positive, and HPV18 has been implicated more in glandular than in squamous lesions. A strong clinical case for the application of HPV

  11. Management of hemopoietic neoplasias during pregnancy.

    PubMed

    Paydas, Semra

    2016-08-01

    Hemopoietic neoplasias are unique cancers generally affecting bone marrow, and requires a special attention for disease control and also their complications. When these neoplastic disorders accompany to pregnancy there are many risks both for mother and foetus. Diagnostic difficulties due to the limited use of imaging modalities is essential in pregnant women. On the other hand suboptimal using of the anti-neoplastic drugs and their higher toxicity in mother and foetus must be considered in the management of these neoplastic disorders. Due to the lack of therapeutic guidelines in these cases, team approach is essential and therapy requires to the use the art of medicine. PMID:27283927

  12. Chemoresistant gestational trophoblastic neoplasia: a case report.

    PubMed

    Cp, Sudha; M, Sahana

    2014-07-01

    Gestational trophoblastic neoplasia (GTN) is a disease of women in reproductive age. It is one of the most chemotherapy responsive and highly curable cancer. It is diagnosed when there is clinical, radiologic, pathologic, and/or hormonal evidence of persistent or relapsed gestational trophoblastic disease. In most instances, it is cured by surgical evacuation of the uterus. If persistent, it is treated with chemotherapy which provides response in >90% of the cases. In the unresponsive persistent cases and if the women has completed her child bearing, hysterectomy is generally recommended. Here, we report a rare case of chemoresistant GTN which was confirmed to be placental-site trophoblastic tumour (PSTT) on biopsy.

  13. Molecular signatures of thyroid follicular neoplasia.

    PubMed

    Borup, Rehannah; Rossing, Maria; Henao, Ricardo; Yamamoto, Yohei; Krogdahl, Annelise; Godballe, Christian; Winther, Ole; Kiss, Katalin; Christensen, Lise; Høgdall, Estrid; Bennedbaek, Finn; Nielsen, Finn Cilius

    2010-09-01

    The molecular pathways leading to thyroid follicular neoplasia are incompletely understood, and the diagnosis of follicular tumors is a clinical challenge. To provide leads to the pathogenesis and diagnosis of the tumors, we examined the global transcriptome signatures of follicular thyroid carcinoma (FC) and normofollicular adenoma (FA) as well as fetal/microFA (fetal adenoma). Carcinomas were strongly enriched in transcripts encoding proteins involved in DNA replication and mitosis corresponding to increased number of proliferating cells and depleted number of transcripts encoding factors involved in growth arrest and apoptosis. In the latter group, the combined loss of transcripts encoding the nuclear orphan receptors NR4A1 and NR4A3, which were recently shown to play a causal role in hematopoetic neoplasia, was noteworthy. The analysis of differentially expressed transcripts provided a mechanism for cancer progression, which is why we exploited the results in order to generate a molecular classifier that could identify 95% of all carcinomas. Validation employing public domain and cross-platform data demonstrated that the signature was robust and could diagnose follicular nodules originating from different geographical locations and platforms with similar accuracy. We came to the conclusion that down-regulation of factors involved in growth arrest and apoptosis may represent a decisive step in the pathogenesis of FC. Moreover, the described molecular pathways provide an accurate and robust genetic signature for the diagnosis of FA and FC. PMID:20668010

  14. Pancreatic paracoccidioidomycosis simulating malignant neoplasia: case report.

    PubMed

    Lima, Talles Bazeia; Domingues, Maria Aparecida Custódio; Caramori, Carlos Antonio; Silva, Giovanni Faria; de Oliveira, Cássio Vieira; Yamashiro, Fábio da Silva; Franzoni, Letícia de Campos; Sassaki, Lígia Yukie; Romeiro, Fernando Gomes

    2013-09-14

    Paracoccidioidomycosis is a systemic granulomatous disease caused by fungus, and must be considered in the differential diagnosis of intra-abdominal tumors in endemic areas. We report a rare case of paracoccidioidomycosis in the pancreas. A 45-year-old man was referred to our institution with a 2-mo history of epigastric abdominal pain that was not diet-related, with night sweating, inappetence, weight loss, jaundice, pruritus, choluria, and acholic feces, without signs of sepsis or palpable tumors. Abdominal ultrasonography (US) showed a solid mass of approximately 7 cm × 5.5 cm on the pancreas head. Abdominal computerized tomography showed dilation of the biliary tract, an enlarged pancreas (up to 4.5 in the head region), with dilation of the major pancreatic duct. The patient underwent exploratory laparotomy, and the surgical description consisted of a tumor, measuring 7 to 8 cm with a poorly-defined margin, adhering to posterior planes and mesenteric vessels, showing an enlarged bile duct. External drainage of the biliary tract, Roux-en-Y gastroenteroanastomosis, lymph node excision, and biopsies were performed, but malignant neoplasia was not found. Microscopic analysis showed chronic pancreatitis and a granulomatous chronic inflammatory process in the choledochal lymph node. Acid-alcohol resistant bacillus and fungus screening were negative. Fine-needle aspiration of the pancreas was performed under US guidance. The smear was compatible with infection by Paracoccidioides brasiliensis. We report a rare case of paracoccidioidomycosis simulating a malignant neoplasia in the pancreas head. PMID:24039371

  15. Spontaneous neoplasia in four captive greater hedgehog tenrecs (Setifer setosus).

    PubMed

    Khoii, Mina K; Howerth, Elizabeth W; Burns, Roy B; Carmichael, K Paige; Gyimesi, Zoltan S

    2008-09-01

    Little information is available about diseases and pathology of species within the family Tenrecidae, including the greater hedgehog tenrec (Setifer setosus), a Madagascan insectivore. This report summarizes necropsy and histopathologic findings of neoplasia in four captive greater hedgehog tenrecs. Although only four animals are included in this report, neoplasia seems to be a common and significant source of morbidity and mortality in greater hedgehog tenrecs. Types of neoplasia identified include a thyroid follicular-solid carcinoma, two urinary bladder transitional cell carcinomas, uterine endometrial polyps, and multicentric B-cell lymphoma. Due to small sample size, no etiology could be determined, but genetics, viral infection, pesticide treatment, nutrition, or other environmental factors might contribute to the development of neoplasia in this species. This is the first report of neoplasia in greater hedgehog tenrecs.

  16. Sorafenib suppresses JNK-dependent apoptosis through inhibition of ZAK.

    PubMed

    Vin, Harina; Ching, Grace; Ojeda, Sandra S; Adelmann, Charles H; Chitsazzadeh, Vida; Dwyer, David W; Ma, Haiching; Ehrenreiter, Karin; Baccarini, Manuela; Ruggieri, Rosamaria; Curry, Jonathan L; Ciurea, Ana M; Duvic, Madeleine; Busaidy, Naifa L; Tannir, Nizar M; Tsai, Kenneth Y

    2014-01-01

    Sorafenib is U.S. Food and Drug Adminstration-approved for the treatment of renal cell carcinoma and hepatocellular carcinoma and has been combined with numerous other targeted therapies and chemotherapies in the treatment of many cancers. Unfortunately, as with other RAF inhibitors, patients treated with sorafenib have a 5% to 10% rate of developing cutaneous squamous cell carcinoma (cSCC)/keratoacanthomas. Paradoxical activation of extracellular signal-regulated kinase (ERK) in BRAF wild-type cells has been implicated in RAF inhibitor-induced cSCC. Here, we report that sorafenib suppresses UV-induced apoptosis specifically by inhibiting c-jun-NH(2)-kinase (JNK) activation through the off-target inhibition of leucine zipper and sterile alpha motif-containing kinase (ZAK). Our results implicate suppression of JNK signaling, independent of the ERK pathway, as an additional mechanism of adverse effects of sorafenib. This has broad implications for combination therapies using sorafenib with other modalities that induce apoptosis. PMID:24170769

  17. Glutamine deprivation stimulates mTOR-JNK-dependent chemokine secretion

    PubMed Central

    Shanware, Naval P.; Bray, Kevin; Eng, Christina H.; Wang, Fang; Follettie, Maximillian; Myers, Jeremy; Fantin, Valeria R.; Abraham, Robert T.

    2014-01-01

    The non-essential amino acid, glutamine, exerts pleiotropic effects on cell metabolism, signalling and stress resistance. Here we demonstrate that short-term glutamine restriction triggers an endoplasmic reticulum (ER) stress response that leads to production of the pro-inflammatory chemokine, interleukin-8 (IL-8). Glutamine deprivation-induced ER stress triggers colocalization of autophagosomes, lysosomes and the Golgi into a subcellular structure whose integrity is essential for IL-8 secretion. The stimulatory effect of glutamine restriction on IL-8 production is attributable to depletion of tricarboxylic acid cycle intermediates. The protein kinase, mTOR, is also colocalized with the lysosomal membrane clusters induced by glutamine deprivation, and inhibition of mTORC1 activity abolishes both endomembrane reorganization and IL-8 secretion. Activated mTORC1 elicits IL8 gene expression via the activation of an IRE1-JNK signalling cascade. Treatment of cells with a glutaminase inhibitor phenocopies glutamine restriction, suggesting that these results will be relevant to the clinical development of glutamine metabolism inhibitors as anticancer agents. PMID:25254627

  18. Disruption of PPARγ signaling results in mouse prostatic intraepithelial neoplasia involving active autophagy

    PubMed Central

    Jiang, Ming; Fernandez, Suzanne; Jerome, W. Gray; He, Yue; Yu, Xiuping; Cai, Hui; Boone, Braden; Yi, Yajun; Magnuson, Mark A.; Roy-Burman, Pradip; Matusik, Robert J.; Shappell, Scott B.; Hayward, Simon W.

    2009-01-01

    Peroxisome proliferator-activated receptor-gamma (PPARγ) regulates the interface between cellular lipid metabolism, redox status and organelle differentiation. Conditional prostatic epithelial knockout of PPARγ in mice resulted in focal hyperplasia which developed into mouse prostatic intraepithelial neoplasia (mPIN). The grade of PIN became more severe with time. Electron microscopy (EM) showed accumulated secondary lysosomes containing cellular organelles and debris suggestive of autophagy. Consistent with this analysis the autophagy marker LC3 was found to be upregulated in areas of PIN in PPARγ KO tissues. We selectively knocked down PPARγ2 isoform in wild-type mouse prostatic epithelial cells and examined the consequences of this in a tissue recombination model. Histopathologically grafted tissues resembled the conditional PPARγ KO mouse prostates. EM studies of PPARγ- and PPARγ2-deficient epithelial cells in vitro were suggestive of autophagy, consistent with the prostatic tissue analysis. This was confirmed by examining expression of beclin-1 and LC3. Gene expression profiling in PPARγ-/γ2-deficient cells indicated a major dysregulation of cell cycle control and metabolic signaling networks related to peroxisomal and lysosomal maturation, lipid oxidation and degradation. The putative autophagic phenotypes of PPARγ-deficient cells could be rescued by re-expression of either γ1 or γ2 isoform. We conclude that disruption of PPARγ signaling results in autophagy and oxidative stress during mPIN pathogenesis. PMID:19834493

  19. Photodynamic therapy of cervical intraepithelial neoplasia

    NASA Astrophysics Data System (ADS)

    Inada, Natalia M.; Lombardi, Welington; Leite, Marieli F. M.; Trujillo, Jose R.; Kurachi, Cristina; Bagnato, Vanderlei S.

    2014-03-01

    Photodynamic therapy (PDT) is a technique that has been used for the treatment of tumors, especially in Gynecology. The photodynamic reaction is based on the production of reactive oxygen species after the activation of a photosensitizer. Advantages of the PDT in comparison to the surgical resection are: ambulatory treatment and tissue recovery highly satisfactory, through a non-invasive procedure. The cervical intraepithelial neoplasia (CIN) grades I and II presents potential indications for PDT. The aim of the proposed study is to evaluate the safety and efficacy of the PDT for the diagnostics and treatment of CIN I and II. The equipment and the photosensitizer are produced in Brazil with a representative low cost. It is possible to visualize the fluorescence of the cervix and to treat the lesions, without side effects. The proposed clinical protocol shows great potential to become a public health technique.

  20. T cells, precocious aging, and familial neoplasia.

    PubMed

    Fudenberg, H H; Schuman, S H; Goust, J M; Jorgenson, R

    1978-01-01

    A 15-year-old girl presented with precocious aging and was found to have low levels of active and total T cells. Family history revealed a high familial incidence of cancer on both the maternal and paternal sides, and activ T cell levels were found to be low in several living family members. The patient developed osteogenic sarcoma 13 months after initial study. Since our previous studies have reported low active and total T cells in patients with cancer, the present results suggest that subjects with low active T cells should be monitored frequently to detect possible neoplasia in it early stages. They also suggest that impaired cellular immunity in humans is associated with, if not the cause of, accelerated aging. PMID:304823

  1. Anal Warts and Anal Intradermal Neoplasia

    PubMed Central

    Echenique, Ignacio; Phillips, Benjamin R.

    2011-01-01

    For the last five millennia we have been dealing with the annoyance of verrucas. Anogenital human papillomavirus (HPV) infection is the most common sexually transmitted disease in the United States and is increasing in incidence. As in other gastrointestinal conditions, HPV infection can lead to a stepwise transition from normal cells to dysplastic cells and then to invasive anal cancer. Knowledge of the natural history of HPV infection, risk factors, diagnostic tools, and therapeutic methods gives us the tools to adequately prevent, evaluate, treat, and counsel our patients. In this review, the authors detail the diagnosis, management, and treatment of anal condyloma and anal intraepithelial neoplasia with a focus on prevention, early detection, and treatment using current data and technology. PMID:22379403

  2. Chemoresistant Gestational Trophoblastic Neoplasia: A Case Report

    PubMed Central

    M, Sahana

    2014-01-01

    Gestational trophoblastic neoplasia (GTN) is a disease of women in reproductive age. It is one of the most chemotherapy responsive and highly curable cancer. It is diagnosed when there is clinical, radiologic, pathologic, and/or hormonal evidence of persistent or relapsed gestational trophoblastic disease. In most instances, it is cured by surgical evacuation of the uterus. If persistent, it is treated with chemotherapy which provides response in >90% of the cases. In the unresponsive persistent cases and if the women has completed her child bearing, hysterectomy is generally recommended. Here, we report a rare case of chemoresistant GTN which was confirmed to be placental-site trophoblastic tumour (PSTT) on biopsy. PMID:25177610

  3. Peripheral Calcifying Epithelial Odontogenic Tumour Mimicking a Gingival Inflammation: A Diagnostic Dilemma

    PubMed Central

    de Carvalho, Danielle Lima Corrêa; do Canto, Alan Motta; Eduardo, Fernanda de Paula; Bezinelli, Letícia Mello

    2016-01-01

    The calcifying epithelial odontogenic tumour (CEOT) is an extremely rare benign neoplasia, accounting for approximately 1% of all odontogenic tumours. CEOT can have two clinical manifestations: central or intraosseous (94% of the cases) and peripheral or extraosseous (6% of the cases). Although the latter is less common, the peripheral variant has been described as an insidious lesion, since it is usually asymptomatic and may be erroneously mistaken with gingival hyperplasia, hamartomas, or even metastasis of malignant neoplasia. We report a case of a young male patient presenting with a peripheral CEOT in the mandibular posterior region, mimicking a located gingival inflammation. PMID:27807486

  4. [Clinical characteristics of multiple endocrine neoplasia].

    PubMed

    Conte-Devolx, Bernard; Niccoli, Patricia

    2010-01-01

    Multiple endocrine neoplasia type 1 (MEN1) and type 2 (MEN2) are autosomal dominant inherited multiglandular diseases with familial and individual age-related penetrance and variable expression. The most frequent endocrine features of MEN1 are parathyroid involvement (> 95%), duodeno-pancreatic endocrine tissue involvement (80%), pituitary adenoma (30%), and adrenal cortex tumors (25%), with no clear syndromic variants. Identification of the germline MEN1 mutation confirms the diagnosis, but there is no phenotype-genotype correlation. All patients with MEN2 have medullary thyroid carcinoma (MTC). The most distinctive MEN2 variants are MEN2A (MTC+pheochromocytoma+hyperparathyroidism), MEN2B (MTC+pheo), and isolated familial MTC (FMTC). The prognosis of MEN2 is linked to the progression of MTC, which depends mainly on the stage at diagnosis and the quality of initial surgical treatment. This emphasizes the need for early diagnosis and management. The specific RET codon mutation correlates with the MEN2 syndromic variant and with the age of onset and aggressiveness of MTC. Consequently, RET mutational status should guide major management decisions, such as whether and when to perform thyroidectomy. PMID:20669560

  5. Relationship of ECL cells and gastric neoplasia.

    PubMed Central

    Waldum, H. L.; Brenna, E.; Sandvik, A. K.

    1998-01-01

    The enterochromaffin-like (ECL) cell in the oxyntic mucosa has a key role in the regulation of gastric secretion since it synthesizes and releases the histamine regulating the acid secretion from the parietal cell. Gastrin is the main regulator of the ECL cell function and growth. Long-term hypergastrinemia induces ECL cell hyperplasia, and if continued, neoplasia. ECL cell carcinoids occur in man after long-term hypergastrinemia in conditions like pernicious anemia and gastrinoma. There is also accumulating evidence that a proportion of gastric carcinomas of the diffuse type is derived from the ECL cell. Furthermore, the ECL cell may, by producing substances with angiogenic effects (histamine and basic fibroblast growth factor), be particularly prone to develop malignant tumors. Although the general opinion is that gastrin itself has a direct effect on the oxyntic mucosal stem cell, it cannot be excluded that the general trophic effect of gastrin on the oxyntic mucosa is mediated by histamine or other substances from the ECL cell, and that the ECL cell, therefore, could play a role also in the tumorigenesis/carcinogenesis of gastric carcinomas of intestinal type. PMID:10461363

  6. Multiple endocrine neoplasia type 2 and RET: from neoplasia to neurogenesis

    PubMed Central

    Hansford, J.; Mulligan, L.

    2000-01-01

    Multiple endocrine neoplasia type 2 (MEN 2) is an inherited cancer syndrome characterised by medullary thyroid carcinoma (MTC), with or without phaeochromocytoma and hyperparathyroidism. MEN 2 is unusual among cancer syndromes as it is caused by activation of a cellular oncogene, RET. Germline mutations in the gene encoding the RET receptor tyrosine kinase are found in the vast majority of MEN 2 patients and somatic RET mutations are found in a subset of sporadic MTC. Further, there are strong associations of RET mutation genotype and disease phenotype in MEN 2 which have led to predictions of tissue specific requirements and sensitivities to RET activity. Our ability to identify genetically, with high accuracy, subjects with MEN 2 has revolutionised our ability to diagnose, predict, and manage this disease. In the past few years, studies of RET and its normal ligand and downstream interactions and the signalling pathways it activates have clarified our understanding of the roles played by RET in normal cell survival, proliferation, and differentiation, as well as in disease. Here, we review the current knowledge of the normal functions of RET and the effects of mutations of this gene in tumorigenesis and in normal development.


Keywords: multiple endocrine neoplasia type 2; RET; receptor tyrosine kinase PMID:11073534

  7. A Case of Solitary Nonvascularized Corneal Epithelial Dysplasia

    PubMed Central

    Morii, Tomoya; Sumioka, Takayoshi; Izutani-Kitano, Ai; Takada, Yukihisa; Okada, Yuka; Kao, Winston W.-Y.; Saika, Shizuya

    2016-01-01

    Background. Epithelial dysplasia is categorized as conjunctival/corneal intraepithelial neoplasia which is a precancerous lesion. The lesion is usually developed at the limbal region and grows towards central cornea in association with neovascularization into the lesion. Here, we report a case of isolated nonvascularized corneal epithelial dysplasia surrounded by normal corneal epithelium with immune histochemical finding of ocular surface tissues cytokeratins, for example, keratin 13 and keratin 12. Case Presentation. A 76-year-old man consulted us for visual disturbance with localized opacification of the corneal epithelium in his left eye. His visual acuity was 20/20 and 20/200 in his right and left eye, respectively. Slit lamp examination showed a whitish plaque-like lesion at the center of his left corneal epithelium. No vascular invasion to the lesion was found. The lesion was surgically removed and subjected to histopathological examination and diagnosed as epithelial dysplasia. Amyloidosis was excluded by direct fast scarlet 4BS (DFS) staining. Immunohistochemistry showed that the dysplastic epithelial cells express keratin 13 and vimentin, but not keratin 12, indicating that the neoplastic epithelial cells lacked corneal-type epithelium differentiation. Conclusions. The lesion was diagnosed as nonvascularized epithelial dysplasia of ocular surface. Etiology of the lesion is not known. PMID:27042371

  8. SCRIB expression is deregulated in human prostate cancer, and its deficiency in mice promotes prostate neoplasia

    PubMed Central

    Pearson, Helen B.; Perez-Mancera, Pedro A.; Dow, Lukas E.; Ryan, Andrew; Tennstedt, Pierre; Bogani, Debora; Elsum, Imogen; Greenfield, Andy; Tuveson, David A.; Simon, Ronald; Humbert, Patrick O.

    2011-01-01

    Loss of cellular polarity is a hallmark of epithelial cancers, raising the possibility that regulators of polarity have a role in suppressing tumorigenesis. The Scribble complex is one of at least three interacting protein complexes that have a critical role in establishing and maintaining epithelial polarity. In human colorectal, breast, and endometrial cancers, expression of the Scribble complex member SCRIB is often mislocalized and deregulated. Here, we report that Scrib is indispensable for prostate homeostasis in mice. Scrib heterozygosity initiated prostate hyperplasia, while targeted biallelic Scrib loss predisposed mice to prostate intraepithelial neoplasia. Mechanistically, Scrib was shown to negatively regulate the MAPK cascade to suppress tumorigenesis. Further analysis revealed that prostate-specific loss of Scrib in mice combined with expression of an oncogenic Kras mutation promoted the progression of prostate cancer that recapitulated the human disease. The clinical significance of the work in mice was highlighted by our observation that SCRIB deregulation strongly correlated with poor survival in human prostate cancer. These data suggest that the polarity network could provide a new avenue for therapeutic intervention. PMID:21965329

  9. Aquaporin water channels in the mammary gland: from physiology to pathophysiology and neoplasia.

    PubMed

    Mobasheri, Ali; Barrett-Jolley, Richard

    2014-03-01

    Aquaporins are membrane proteins that play fundamental roles in water and small solute transport across epithelial and endothelial barriers. Recent studies suggest that several aquaporin proteins are present in the mammary gland. Immunohistochemical techniques have confirmed the presence of aquaporin 1 (AQP1) and AQP3 water channels in rat, mouse, bovine and human mammary glands. Studies suggest that in addition to AQP1 and AQP3 AQP4, AQP5 and AQP7 proteins are expressed in different locations in the mammary gland. Aquaporins play key roles in tumor biology and are involved in cell growth, migration and formation of ascites via increased water permeability of micro-vessels. Emerging evidence suggests that expression of these proteins is altered in mammary tumors and in breast cancer cell lines although it is not yet clear whether this is a cause or a consequence of neoplastic development. This review analyzes the expression and potential functional roles of aquaporin water channels in the mammary gland. The physiological mechanisms involved in the transport of water and small solutes across mammary endothelial and epithelial barriers are discussed in the context of milk production and lactation. This paper also reviews papers from the recent cancer literature that implicate aquaporins in mammary neoplasia.

  10. Putting the brakes on mammary tumorigenesis: Loss of STAT1 predisposes to intraepithelial neoplasias

    PubMed Central

    Schneckenleithner, Christine; Bago-Horvath, Zsuzsanna; Dolznig, Helmut; Neugebauer, Nina; Kollmann, Karoline; Kolbe, Thomas; Decker, Thomas; Kerjaschki, Dontscho; Wagner, Kay-Uwe; Müller, Mathias; Stoiber, Dagmar; Sexl, Veronika

    2011-01-01

    Multiparous Stat1−/− mice spontaneously develop mammary tumors with increased incidence: at an average age of 12 months, 55% of the animals suffer from mammary cancer, although the histopathology is heterogeneous. We consistently observed mosaic expression or down-regulation of STAT1 protein in wild-type mammary cancer evolving in the control group. Transplantation experiments show that tumorigenesis in Stat1−/− mice is partially influenced by impaired CTL mediated tumor surveillance. Additionally, STAT1 exerts an intrinsic tumor suppressing role by controlling and blocking proliferation of the mammary epithelium. Loss of STAT1 in epithelial cells enhances cell growth in both transformed and primary cells. The increased proliferative capacity leads to the loss of structured acini formation in 3D-cultures. Analogous effects were observed when Irf1−/− epithelial cells were used. Accordingly, the rate of mammary intraepithelial neoplasias (MINs) is increased in Stat1−/− animals: MINs represent the first step towards mammary tumors. The experiments characterize STAT1/IRF1 as a key growth inhibitory and tumor suppressive signaling pathway that prevents mammary cancer formation by maintaining growth control. Furthermore, they define the loss of STAT1 as a predisposing event via enhanced MIN formation. PMID:22185785

  11. [Heredity in renal and prostatic neoplasia].

    PubMed

    Prayer Galetti, T; D'Arrigo, L; De Zorzi, L; Patarnello, T

    1997-09-01

    There is an ever growing report of data supporting the evidence that accumulated genetic changes underlie the development of neoplasia. The paradigma of this multistep process is colon cancer were cancer onset is associated, over decades, with at least seven genetic events. The number of genetic alterations increases moving from adenomatous lesions to colon cancer and, although the genetic alterations occur according to a preferred sequence, the total accumulation of changes rather than their sequential order is responsible of tumor biological behavior. It is noteworthy that, at least for this neoplasia, carcinogenesis appears to arise as a result of the mutational activation of oncogenes coupled with the mutational inactivation of tumor suppressor genes. In some cases mutant suppressor genes appear to exert a phenotypic effect even when present in the heterozygous state thus been non "recessive" at the cellular level. The general features of this model may apply also to renal cell cancer (RCC) and prostate cancer (CaP). Extensive literature exists on the cytogenetic and molecular findings in RCC. Only 2% of RCC are familiar, but molecular genetic studies of these cancers have provided important informations on RCC pathogenesis. As with other cancers, familiar RCC is characterized by an early age of onset and frequent multicentricity. A pathological classification useful in studying these patients subdivide renal cancers in papillary (pRCC) and non papillary (RCC) neoplasms. The most common cause of inherited RCC is the Von Hippel Lindau disease (VHL) a dominantly inherited multisystem disorder characterized by retinal and cerebellar hemangioblastomas, pheochromocytomas, pancreatic cysts and RCC. Over 70% of these patients will develop an RCC by their sixth decade. In 1993 the isolation of the tumor suppressor gene in VHL disease at the level of chromosome 3p25-p26 have lead to a better understanding of RCC. Most missense mutations are associated with high risk of

  12. [Heredity in renal and prostatic neoplasia].

    PubMed

    Prayer Galetti, T; D'Arrigo, L; De Zorzi, L; Patarnello, T

    1997-09-01

    There is an ever growing report of data supporting the evidence that accumulated genetic changes underlie the development of neoplasia. The paradigma of this multistep process is colon cancer were cancer onset is associated, over decades, with at least seven genetic events. The number of genetic alterations increases moving from adenomatous lesions to colon cancer and, although the genetic alterations occur according to a preferred sequence, the total accumulation of changes rather than their sequential order is responsible of tumor biological behavior. It is noteworthy that, at least for this neoplasia, carcinogenesis appears to arise as a result of the mutational activation of oncogenes coupled with the mutational inactivation of tumor suppressor genes. In some cases mutant suppressor genes appear to exert a phenotypic effect even when present in the heterozygous state thus been non "recessive" at the cellular level. The general features of this model may apply also to renal cell cancer (RCC) and prostate cancer (CaP). Extensive literature exists on the cytogenetic and molecular findings in RCC. Only 2% of RCC are familiar, but molecular genetic studies of these cancers have provided important informations on RCC pathogenesis. As with other cancers, familiar RCC is characterized by an early age of onset and frequent multicentricity. A pathological classification useful in studying these patients subdivide renal cancers in papillary (pRCC) and non papillary (RCC) neoplasms. The most common cause of inherited RCC is the Von Hippel Lindau disease (VHL) a dominantly inherited multisystem disorder characterized by retinal and cerebellar hemangioblastomas, pheochromocytomas, pancreatic cysts and RCC. Over 70% of these patients will develop an RCC by their sixth decade. In 1993 the isolation of the tumor suppressor gene in VHL disease at the level of chromosome 3p25-p26 have lead to a better understanding of RCC. Most missense mutations are associated with high risk of

  13. [Hematopoietic stem cells and hematopoietic neoplasias].

    PubMed

    Wickenhauser, C

    2002-11-01

    Pluripotent hematopoietic stem cells have been defined as cells with extensive self-renewal capacity and lympho-hematopoietic differentiation potential. Clonal selection of a stem cell as a first step in the progression to neoplasia can be achieved by an alteration of this self-renewal potency. Our current understanding of the pathogenesis of the myeloproliferative disorders including acute myeloid leukemias, chronic myeloproliferative disorders (CMPD) and myelodysplastic syndromes (MDS), is based on the assumption that they represent a clonal disorder resulting from transformation of a hematopoietic stem cell. However, when performing methods for determining X-chromosome inactivation in female patients as a clonality marker, a significant minority of the patients with Philadelphia chromosome negative (Ph(-)) CMPD and MDS exhibit polyclonal proliferation. The implications of these results are not yet clarified and the lack of a proven target cell impairs the understanding of the underlying molecular defect. In this context, altered response to cytokine stimulation in vitro provides indirect information concerning molecular dysregulation. A subset of patients with MPD present with translocations that facilitate molecular investigation and clonality proof. They nearly always result in rearrangements of at least one transcription factor gene. Most of these fusion genes are constitutively active, sending out continuous proliferative and antiapoptotic signals or activate an overlapping set of signalling pathways. The classical example for a balanced translocation is the t(9;22) bcr-abl aberration in chronic myelogeneous leukemia. Many other karyotypic abnormalities have also been associated with CMPD and MDS and involve deletions of chromosomes 20q, 13q, 1q, 7q and 5q as well as trisomy of 8 and 9. Our increased understanding of the hematopoietic stem cell compartment and the molecular basis of regulation of its self-renewal and differentiation bears a direct impact on

  14. Development of germ cell neoplasia in situ in chinchilla rabbits.

    PubMed

    Vigueras-Villaseñor, Rosa María; Montelongo Solís, Paola; Chávez-Saldaña, Margarita; Gutiérrez-Pérez, Oscar; Cortés Trujillo, Lucero; Rojas-Castañeda, Julio César

    2016-05-01

    The present study was designed to describe the development of germ cell neoplasia in situ in Chinchilla rabbit by administration of estradiol. The study was performed in rabbits distributed into two groups: control and 17 β-estradiol. The determination of histological alterations and POU5F1 and c-kit proteins employed as biomarkers for the diagnosis of this neoplasia was carried out. Testicular descent and complete spermatogenesis were observed in the control group. The protein biomarkers were negative. However, in the rabbits treated with estradiol, the testes remained undescended with the gonocytes undifferentiated to spermatogonia. There were histological lesions owing to germ cell neoplasia in situ and positive to POU5F1 and c-kit proteins. These findings indicate that the chinchilla rabbit is an ideal model to study this neoplasia in which the histological characteristics and biomarkers of the disease could be clearly observed. Using this model we suggested that the persisting gonocytes could be responsible for the development of germ cell neoplasia in situ. PMID:26617392

  15. [Myoepithelial differentiation markers in salivary gland neoplasia].

    PubMed

    Scarpellini, F; Marucci, G; Foschini, M P

    2001-12-01

    Salivary gland tumors frequently present myoepithelial cell differentiation that is not always easily identified on routinely stained sections. Recently novel markers of myoepithelium have been studied, such as calponin (CALP), caldesmon (CALD), and smooth muscle myosin heavy chain. These markers, together with smooth muscle actin may be useful tools for identifying myoepithelial cells. We immunohistochemically studied a series of 23 benign and malignant salivary gland tumors using antibodies to these four markers. The tumors were classified as follows: pleomorphic adenoma (n = 8), basal cell adenoma (n = 3), myoepithelioma with plasmacytoid cells (n = 2), epithelial-myoepithelial cell carcinoma (n = 6) and adenoid cystic carcinoma (n = 4). All tumors were positive for at least one of the four markers. CALP and smooth muscle actin were the markers more frequently expressed. Positivity was mostly located in the myoepithelial cells that constitute the external layer of the glandular or tubular neoplastic structures. In poorly differentiated epithelial myoepithelial carcinomas, composed of solid sheets of neoplastic cells and sometimes of clear cells, immunohistochemical staining for myoepithelial markers evidenced rudimentary glandular structures. CALP and smooth muscle actin were positive in the two cases of myoepithelioma with plasmacytoid cells. In conclusion, the combined staining with four markers helps to disclose myoepithelial cell differentiation and can be a useful tool for the correct histopathological diagnosis of salivary gland tumors. Among the four markers studied, CALP and smooth muscle actin were the most useful to identify myoepithelial cell differentiation.

  16. Radiogenic neoplasia in thyroid and mammary clonogens. Progress report, January 1, 1991--December 31, 1991

    SciTech Connect

    Clifton, K.H.

    1991-05-31

    We have developed rat thyroid and mammary clonogen transplantation systems for the study of radiogenic cancer induction at the target cell level in vivo. The epithelial cell populations of both glands contain small subpopulations of cells which are capable of giving rise to monoclonal glandular structures when transplanted and stimulated with appropriate hormones. During the end of the last grant year and the first half of the current grant year, we have completed analyses and summarized for publication: investigations on the relationship between grafted thyroid cell number and the rapidity and degree of reestablishment of the thyroid-hypothalamicpituitary axis in thyroidectomized rats maintained on a normal diet or an iodine deficient diet; studies of the persistence of, and the differentiation potential and functional characteristics of, the TSH- (thyrotropin-) responsive sub-population of clonogens during goitrogenesis, the plateau-phase of goiter growth, and goiter involution; studies of changes in the size of the clonogen sub-population during goitrogenesis, goiter involution and the response to goitrogen rechallenge; and the results of the large carcinogenesis experiment on the nature of the grafted thyroid cell number-dependent suppression of promotion/progression to neoplasia in grafts of radiation-initiated thyroid cells. We are testing new techniques for the culture, cytofluorescent analysis and characterization mammary epithelial cells and of clonogens in a parallel project, and plan to apply similar technology to the thyroid epithelial cells and clonogen population. Data from these studies will be used in the design of future carcinogenesis experiments on neoplastic initiation by high and low LET radiations and on cells interactions during the neoplastic process.

  17. Inflammatory bowel disease associated neoplasia: A surgeon’s perspective

    PubMed Central

    Althumairi, Azah A; Lazarev, Mark G; Gearhart, Susan L

    2016-01-01

    Inflammatory bowel disease (IBD) is associated with increased risk of colorectal cancer (CRC). The risk is known to increase with longer duration of the disease, family history of CRC, and history of primary sclerosing cholangitis. The diagnosis of the neoplastic changes associated with IBD is difficult owing to the heterogeneous endoscopic appearance and inter-observer variability of the pathological diagnosis. Screening and surveillance guidelines have been established which aim for early detection of neoplasia. Several surgical options are available for the treatment of IBD-associated neoplasia. Patients’ morbidities, risk factors for CRC, degree and the extent of neoplasia must be considered in choosing the surgical treatment. A multidisciplinary team including the surgeon, gastroenterologist, pathologist, and the patient who has a clear understanding of the nature of their disease is needed to optimize outcomes. PMID:26811640

  18. Plasminogen activators in human colorectal neoplasia.

    PubMed Central

    Gelister, J S; Mahmoud, M; Lewin, M R; Gaffney, P J; Boulos, P B

    1986-01-01

    A crucial step in the transition from adenomatous polyp to invasive colorectal cancer is the degradation of the epithelial basement membrane. Plasminogen activators may play a part in regulating the extracellular protease environment necessary for this to occur. Both functional and antigenic activity of the two principal activators of plasminogen, tissue plasminogen activator and urokinase, were measured in 30 colorectal cancers, matched samples of mucosa, and eight adenomatous polyps. Both polyps (p less than 0.01) and carcinomas (p less than 0.001) had raised urokinase activities compared with normal mucosa, the activity being highest in the carcinomas. Activity of tissue plasminogen activator, however, was diminished in both polyps (p less than 0.01) and carcinomas (p less than 0.001) compared with normal mucosa, the values being lowest in carcinomas. Plasmin generation by urokinase--in contrast with tissue plasminogen activator--is fibrin independent and thus less subject to physiological control. Images p730-a PMID:3094628

  19. High grade prostatic intraepithelial neoplasia with squamous differentiation

    PubMed Central

    Melissari, M; Beltran, A Lopez; Mazzucchelli, R; Froio, E; Bostwick, D G; Montironi, R

    2006-01-01

    An unusual variant of prostatic intraepithelial neoplasia with prominent and extensive squamous differentiation is described. The lesion was identified in the transition zone of a 79 year old man with a three year history of increasing urinary obstructive symptoms and a clinical diagnosis of benign prostatic hyperplasia who underwent simple prostatectomy. Two years after surgery, prostatic biopsies showed atrophy and mild chronic inflammation, with no evidence of malignancy. This unusual intraepithelial lesion seems not to have been described before and may represent a new variant of high grade prostatic intraepithelial neoplasia (HGPIN) with squamous differentiation. PMID:16567473

  20. Progressive squamous epithelial neoplasia in K14-human papillomavirus type 16 transgenic mice.

    PubMed Central

    Arbeit, J M; Münger, K; Howley, P M; Hanahan, D

    1994-01-01

    To model human papillomavirus-induced neoplastic progression, expression of the early region of human papillomavirus type 16 (HPV16) was targeted to the basal cells of the squamous epithelium in transgenic mice, using a human keratin 14 (K14) enhancer/promoter. Twenty-one transgenic founder mice were produced, and eight lines carrying either wild-type or mutant HPV16 early regions that did not express the E1 or E2 genes were established. As is characteristic of human cancers, the E6 and E7 genes remained intact in these mutants. The absence of E1 or E2 function did not influence the severity of the phenotype that eventually developed in the transgenic mice. Hyperplasia, papillomatosis, and dysplasia appeared at multiple epidermal and squamous mucosal sites, including ear and truncal skin, face, snout and eyelids, and anus. The ears were the most consistently affected site, with pathology being present in all lines with 100% penetrance. This phenotype also progressed through discernible stages. An initial mild hyperplasia was followed by hyperplasia, which further progressed to dysplasia and papillomatosis. During histopathological progression, there was an incremental increase in cellular DNA synthesis, determined by 5-bromo-2'-deoxyuridine incorporation, and a profound perturbation in keratinocyte terminal differentiation, as revealed by immunohistochemistry to K5, K14, and K10 and filaggrin. These K14-HPV16 transgenic mice present an opportunity to study the role of the HPV16 oncogenes in the neoplastic progression of squamous epithelium and provide a model with which to identify genetic and epigenetic factors necessary for carcinogenesis. Images PMID:7515971

  1. Association of human immunodeficiency virus-induced immunosuppression with human papillomavirus infection and cervical intraepithelial neoplasia.

    PubMed

    Henry, M J; Stanley, M W; Cruikshank, S; Carson, L

    1989-02-01

    Human papillomavirus infection plays an important causal role in cervical intraepithelial neoplasia and carcinoma. The rate of infection with human papillomavirus as well as the incidence of cervical intraepithelial neoplasia and carcinoma are increased in immunosuppressed patients. We report a possible association between infection with human immunodeficiency virus and cervical intraepithelial neoplasia with human papillomavirus infection.

  2. In vivo and in vitro hyperspectral imaging of cervical neoplasia

    NASA Astrophysics Data System (ADS)

    Wang, Chaojian; Zheng, Wenli; Bu, Yanggao; Chang, Shufang; Tong, Qingping; Zhang, Shiwu; Xu, Ronald X.

    2014-02-01

    Cervical cancer is a prevalent disease in many developing countries. Colposcopy is the most common approach for screening cervical intraepithelial neoplasia (CIN). However, its clinical efficacy heavily relies on the examiner's experience. Spectroscopy is a potentially effective method for noninvasive diagnosis of cervical neoplasia. In this paper, we introduce a hyperspectral imaging technique for noninvasive detection and quantitative analysis of cervical neoplasia. A hyperspectral camera is used to collect the reflectance images of the entire cervix under xenon lamp illumination, followed by standard colposcopy examination and cervical tissue biopsy at both normal and abnormal sites in different quadrants. The collected reflectance data are calibrated and the hyperspectral signals are extracted. Further spectral analysis and image processing works are carried out to classify tissue into different types based on the spectral characteristics at different stages of cervical intraepithelial neoplasia. The hyperspectral camera is also coupled with a lab microscope to acquire the hyperspectral transmittance images of the pathological slides. The in vivo and the in vitro imaging results are compared with clinical findings to assess the accuracy and efficacy of the method.

  3. Hematopoietic Neoplasias in Horses: Myeloproliferative and Lymphoproliferative Disorders

    PubMed Central

    MUÑOZ, Ana; RIBER, Cristina; TRIGO, Pablo; CASTEJÓN, Francisco

    2010-01-01

    Leukemia, i.e., the neoplasia of one or more cell lines of the bone marrow, although less common than in other species, it is also reported in horses. Leukemia can be classified according to the affected cells (myeloproliferative or lymphoproliferative disorders), evolution of clinical signs (acute or chronic) and the presence or lack of abnormal cells in peripheral blood (leukemic, subleukemic and aleukemic leukemia). The main myeloproliferative disorders in horses are malignant histiocytosis and myeloid leukemia, the latter being classified as monocytic and myelomonocytic, granulocytic, primary erythrocytosis or polycythemia vera and megakaryocytic leukemia. The most common lymphoproliferative disorders in horses are lymphoid leukemia, plasma cell or multiple myeloma and lymphoma. Lymphoma is the most common hematopoietic neoplasia in horses and usually involves lymphoid organs, without leukemia, although bone marrow may be affected after metastasis. Lymphoma could be classified according to the organs involved and four main clinical categories have been established: generalized-multicentric, alimentary-gastrointestinal, mediastinal-thymic-thoracic and cutaneous. The clinical signs, hematological and clinical pathological findings, results of bone marrow aspirates, involvement of other organs, prognosis and treatment, if applicable, are presented for each type of neoplasia. This paper aims to provide a guide for equine practitioners when approaching to clinical cases with suspicion of hematopoietic neoplasia. PMID:24833969

  4. Reptile neoplasia at the Philadelphia Zoological Garden, 1901-2002.

    PubMed

    Sykes, John M; Trupkiewicz, John G

    2006-03-01

    A retrospective study of neoplasia in reptiles held at the Philadelphia Zoological Garden was conducted. A total of 3,684 original necropsy reports for the period 1901-2002 were reviewed and revealed 86 cases of neoplasia. Original glass slides or re-cuts from paraffin-embedded tissue blocks were examined for confirmation of the original diagnosis. At necropsy, a total of six neoplasms were identified in six of 490 chelonians (1.2%), 22 neoplasms in 19 of 736 lizards (3.0%), and 58 neoplasms in 53 of 1,835 snakes (2.9%). An additional 12 neoplasms were found in biopsies of one turtle and 10 snakes. In the chelonians, all the neoplasms were seen in turtles, four of six tumors were malignant (66%) and no organ predilection was noted. For lizards, the liver was the most commonly affected organ, with 7 of 22 primary neoplasms (31%). Multiple tumor types were identified in three lizards (15%), metastasis occurred in five cases (25%), and malignant tumors were identified in 16 cases (73%). In snakes, the liver was most frequently affected by neoplasia at necropsy, with 13 of 58 primary neoplasms (22%); multiple types of neoplasm were identified in five cases (10%) and metastasis in six (9%); and 42 tumors (80%) were diagnosed as malignant. When biopsies were included for snakes, however, the skin was the most commonly affected organ, with 17 of 69 neoplasms (24%). One of five lizards (20%) and four of six snakes (66%) with metastasis also had a second primary neoplasm. Since 1967, the incidence of lizard neoplasia has increased from 0.7% to 5.9%, and snake neoplasia has increased from 2.6% to 9.3%.

  5. Pten Regulates Epithelial Cytodifferentiation during Prostate Development

    PubMed Central

    Lokody, Isabel B.; Francis, Jeffrey C.; Gardiner, Jennifer R.; Erler, Janine T.; Swain, Amanda

    2015-01-01

    Gene expression and functional studies have indicated that the molecular programmes involved in prostate development are also active in prostate cancer. PTEN has been implicated in human prostate cancer and is frequently mutated in this disease. Here, using the Nkx3.1:Cre mouse strain and a genetic deletion approach, we investigate the role of Pten specifically in the developing mouse prostate epithelia. In contrast to its role in other developing organs, this gene is dispensable for the initial developmental processes such as budding and branching. However, as cytodifferentiation progresses, abnormal luminal cells fill the ductal lumens together with augmented epithelial proliferation. This phenotype resembles the hyperplasia seen in postnatal Pten deletion models that develop neoplasia at later stages. Consistent with this, gene expression analysis showed a number of genes affected that are shared with Pten mutant prostate cancer models, including a decrease in androgen receptor regulated genes. In depth analysis of the phenotype of these mice during development revealed that loss of Pten leads to the precocious differentiation of epithelial cells towards a luminal cell fate. This study provides novel insight into the role of Pten in prostate development as part of the process of coordinating the differentiation and proliferation of cell types in time and space to form a functional organ. PMID:26076167

  6. Anchoring Hepatic Gene Expression with Development of Fibrosis and Neoplasia in a Toxicant-Induced Fish Model of Liver Injury

    PubMed Central

    Van Wettere, Arnaud J.; Law, J. Mac; Hinton, David E.; Kullman, Seth W.

    2014-01-01

    Fish have been used as laboratory models to study hepatic development and carcinogenesis but not for pathogenesis of hepatic fibrosis. In this study, a dimethylnitrosamine-induced fish model of hepatic injury was developed in Japanese medaka (Oryzias latipes) and gene expression was anchored with the development of hepatic fibrosis and neoplasia. Exposed livers exhibited mild hepatocellular degenerative changes 2 weeks post-exposure. Within six weeks hepatic fibrosis/cirrhosis was evident with development of neoplasia by 10 weeks. Stellate cell activation and development of fibrosis was associated with upregulation of tgfb1,tgfb receptor 2, smad3a, smad3b, ctnnb1, myc, mmp2, mmp14a, mmp14b, timp2a, timp2b, timp3, col1a1a, and col1a1b, and a less pronounced increase in mmp13 and col4a1expression. Tgfb receptor I expression was unchanged. Immunohistochemistry suggested that biliary epithelial cells and stellate cells were the main producers of TGF-β1. This study identified a group of candidate genes likely to be involved in the development of hepatic fibrosis, and demonstrated that the TGF-β pathway likely plays a major role in the pathogenesis. These results support the medaka as a viable fish model of hepatic fibrosis. PMID:23197195

  7. Evaluation of DNA single and double strand breaks in women with cervical neoplasia based on alkaline and neutral comet assay techniques.

    PubMed

    Cortés-Gutiérrez, Elva I; Hernández-Garza, Fernando; García-Pérez, Jorge O; Dávila-Rodríguez, Martha I; Aguado-Barrera, Miguel E; Cerda-Flores, Ricardo M

    2012-01-01

    A hospital-based unmatched case-control study was performed in order to determine the relation of DNA single (ssb) and double (dsb) strand breaks in women with and without cervical neoplasia. Cervical epithelial cells of 30 women: 10 with low grade squamous intraepithelial lesions (LG-SIL), 10 with high-grade SIL (HG-SIL), and 10 without cervical lesions were evaluated using alkaline and neutral comet assays. A significant increase in global DNA damage (ssb + dsb) and dsb was observed in patients with HG-SIL (48.90 ± 12.87 and 23.50 ± 13.91), patients with LG-SIL (33.60 ± 14.96 and 11.20 ± 5.71), and controls (21.70 ± 11.87 and 5.30 ± 5.38; resp.). Pearson correlation coefficient reveled a strong relation between the levels ssb and dsb (r(2) = 0.99, P = 0.03, and r(2) = 0.94, P = 0.16, resp.) and progression of neoplasia. The increase of dsb damage in patients with HG-SIL was confirmed by DNA breakage detection-FISH (DBD-FISH) on neutral comets. Our results argue in favor of a real genomic instability in women with cervical neoplasia, which was strengthened by our finding of a higher proportion of DNA dsb. PMID:23093842

  8. Evaluation of DNA Single and Double Strand Breaks in Women with Cervical Neoplasia Based on Alkaline and Neutral Comet Assay Techniques

    PubMed Central

    Cortés-Gutiérrez, Elva I.; Hernández-Garza, Fernando; García-Pérez, Jorge O.; Dávila-Rodríguez, Martha I.; Aguado-Barrera, Miguel E.; Cerda-Flores, Ricardo M.

    2012-01-01

    A hospital-based unmatched case-control study was performed in order to determine the relation of DNA single (ssb) and double (dsb) strand breaks in women with and without cervical neoplasia. Cervical epithelial cells of 30 women: 10 with low grade squamous intraepithelial lesions (LG-SIL), 10 with high-grade SIL (HG-SIL), and 10 without cervical lesions were evaluated using alkaline and neutral comet assays. A significant increase in global DNA damage (ssb + dsb) and dsb was observed in patients with HG-SIL (48.90 ± 12.87 and 23.50 ± 13.91), patients with LG-SIL (33.60 ± 14.96 and 11.20 ± 5.71), and controls (21.70 ± 11.87 and 5.30 ± 5.38; resp.). Pearson correlation coefficient reveled a strong relation between the levels ssb and dsb (r2 = 0.99, P = 0.03, and r2 = 0.94, P = 0.16, resp.) and progression of neoplasia. The increase of dsb damage in patients with HG-SIL was confirmed by DNA breakage detection-FISH (DBD-FISH) on neutral comets. Our results argue in favor of a real genomic instability in women with cervical neoplasia, which was strengthened by our finding of a higher proportion of DNA dsb. PMID:23093842

  9. Increasing expression of gastrointestinal phenotypes and p53 along with histologic progression of intraductal papillary neoplasia of the liver.

    PubMed

    Shimonishi, Tomonori; Zen, Yoh; Chen, Tse-Ching; Chen, Miin-Fu; Jan, Yi-Yin; Yeh, Ta-Sen; Nimura, Yuji; Nakanuma, Yasuni

    2002-05-01

    Intraductal papillary neoplasia of the liver (IPN-L) was recently proposed as the name for intraductal papillary proliferation of neoplastic biliary epithelium with a fine fibrovascular stalk resembling intraductal papillary mucinous neoplasm of the pancreas. We histochemically and immunohistochemically examined IPN-L alone or associated with hepatolithiasis, with an emphasis on the gastrointestinal metaplasia, nuclear p53 expression, and histologic progression. A total of 66 cases of IPN-L were divided into 4 groups: group 1, IPN-L with low-grade dysplasia (13 cases); group 2, IPN-L with high-grade dysplasia (20 cases); group 3, IPN-L lined with carcinoma in situ and no or microinvasion (19 cases); and group 4, group 3 with distinct invasive carcinoma (14 cases). It is suggested that IPN-L progresses from group 1 to group 4. As controls, 20 cases of nonneoplastic intrahepatic large bile ducts and 17 cases of nonpapillary invasive intrahepatic cholangiocarcinoma (ICC) were used. Biliary epithelial hypersecretion of sialomucin rather than sulfomucin was prevalent in IPN-L, and this was associated with the progression of INP-L. Immunohistochemically, cytokeratin (CK) 20 and MUC2, a gastrointestinal marker, were expressed more frequently in IPN-L than in nonneoplastic bile ducts and nonpapillary ICC (P <0.01), and their incidence were significantly increased in parallel with the progression of IPN-L (P < 0.01). In contrast, expression of CK 7, a biliary marker, was decreased in IPN-L compared with nonpapillary ICC. Nuclear p53 immunostaining was detected in 30% of IPN-L as a whole and increased in tandem with the progression of IPN-L (P < 0.01). It is suggested that IPN-L forms a spectrum of biliary epithelial neoplasia with frequent gastrointestinal metaplasia, different from the usual nonpapillary ICC, and shows stepwise progression from the perspective of mucin profile, gastrointestinal metaplasia, and p53 nuclear expression. PMID:12094375

  10. Innate immunity gene polymorphisms and the risk of colorectal neoplasia

    PubMed Central

    Berndt, Sonja I.

    2013-01-01

    Inherited variation in genes that regulate innate immunity and inflammation may contribute to colorectal neoplasia risk. To evaluate this association, we conducted a nested case–control study of 451 colorectal cancer cases, 694 colorectal advanced adenoma cases and 696 controls of European descent within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. A total of 935 tag single-nucleotide polymorphisms (SNPs) in 98 genes were evaluated. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association with colorectal neoplasia. Sixteen SNPs were associated with colorectal neoplasia risk at P < 0.01, but after adjustment for multiple testing, only rs2838732 (ITGB2) remained suggestively associated with colorectal neoplasia (ORper T allele = 0.68, 95% CI: 0.57–0.83, P = 7.7 × 10–5, adjusted P = 0.07). ITGB2 codes for the CD18 protein in the integrin beta chain family. The ITGB2 association was stronger for colorectal cancer (ORper T allele = 0.41, 95% CI: 0.30–0.55, P = 2.4 × 10− 9) than for adenoma (ORper T allele = 0.84, 95%CI: 0.69–1.03, P = 0.08), but it did not replicate in the validation study. The ITGB2 rs2838732 association was significantly modified by smoking status (P value for interaction = 0.003). Among never and former smokers, it was inversely associated with colorectal neoplasia (ORper T allele = 0.5, 95% CI: 0.37–0.69 and ORper T allele = 0.72, 95% CI: 0.54–0.95, respectively), but no association was seen among current smokers. Other notable findings were observed for SNPs in BPI/LBP and MYD88. Although the results need to be replicated, our findings suggest that genetic variation in inflammation-related genes may be related to the risk of colorectal neoplasia. PMID:23803696

  11. Cervical intraepithelial neoplasia disease progression is associated with increased vaginal microbiome diversity

    PubMed Central

    Mitra, A.; MacIntyre, D. A.; Lee, Y. S.; Smith, A.; Marchesi, J. R.; Lehne, B.; Bhatia, R.; Lyons, D.; Paraskevaidis, E.; Li, J. V.; Holmes, E.; Nicholson, J. K.; Bennett, P. R.; Kyrgiou, M.

    2015-01-01

    Persistent infection with oncogenic Human Papillomavirus (HPV) is necessary for cervical carcinogenesis. Although evidence suggests that the vaginal microbiome plays a functional role in the persistence or regression of HPV infections, this has yet to be described in women with cervical intra-epithelial neoplasia (CIN). We hypothesised that increasing microbiome diversity is associated with increasing CIN severity. llumina MiSeq sequencing of 16S rRNA gene amplicons was used to characterise the vaginal microbiota of women with low-grade squamous intra-epithelial lesions (LSIL; n = 52), high-grade (HSIL; n = 92), invasive cervical cancer (ICC; n = 5) and healthy controls (n = 20). Hierarchical clustering analysis revealed an increased prevalence of microbiomes characterised by high-diversity and low levels of Lactobacillus spp. (community state type-CST IV) with increasing disease severity, irrespective of HPV status (Normal = 2/20,10%; LSIL = 11/52,21%; HSIL = 25/92,27%; ICC = 2/5,40%). Increasing disease severity was associated with decreasing relative abundance of Lactobacillus spp. The vaginal microbiome in HSIL was characterised by higher levels of Sneathia sanguinegens (P < 0.01), Anaerococcus tetradius (P < 0.05) and Peptostreptococcus anaerobius (P < 0.05) and lower levels of Lactobacillus jensenii (P < 0.01) compared to LSIL. Our results suggest advancing CIN disease severity is associated with increasing vaginal microbiota diversity and may be involved in regulating viral persistence and disease progression. PMID:26574055

  12. Cervical intraepithelial neoplasia disease progression is associated with increased vaginal microbiome diversity.

    PubMed

    Mitra, A; MacIntyre, D A; Lee, Y S; Smith, A; Marchesi, J R; Lehne, B; Bhatia, R; Lyons, D; Paraskevaidis, E; Li, J V; Holmes, E; Nicholson, J K; Bennett, P R; Kyrgiou, M

    2015-11-17

    Persistent infection with oncogenic Human Papillomavirus (HPV) is necessary for cervical carcinogenesis. Although evidence suggests that the vaginal microbiome plays a functional role in the persistence or regression of HPV infections, this has yet to be described in women with cervical intra-epithelial neoplasia (CIN). We hypothesised that increasing microbiome diversity is associated with increasing CIN severity. llumina MiSeq sequencing of 16S rRNA gene amplicons was used to characterise the vaginal microbiota of women with low-grade squamous intra-epithelial lesions (LSIL; n = 52), high-grade (HSIL; n = 92), invasive cervical cancer (ICC; n = 5) and healthy controls (n = 20). Hierarchical clustering analysis revealed an increased prevalence of microbiomes characterised by high-diversity and low levels of Lactobacillus spp. (community state type-CST IV) with increasing disease severity, irrespective of HPV status (Normal = 2/20,10%; LSIL = 11/52,21%; HSIL = 25/92,27%; ICC = 2/5,40%). Increasing disease severity was associated with decreasing relative abundance of Lactobacillus spp. The vaginal microbiome in HSIL was characterised by higher levels of Sneathia sanguinegens (P < 0.01), Anaerococcus tetradius (P < 0.05) and Peptostreptococcus anaerobius (P < 0.05) and lower levels of Lactobacillus jensenii (P < 0.01) compared to LSIL. Our results suggest advancing CIN disease severity is associated with increasing vaginal microbiota diversity and may be involved in regulating viral persistence and disease progression.

  13. Plasminogen activators in experimental colorectal neoplasia: a role in the adenoma-carcinoma sequence?

    PubMed Central

    Gelister, J S; Lewin, M R; Driver, H E; Savage, F; Mahmoud, M; Gaffney, P J; Boulos, P B

    1987-01-01

    An important step in the transition from adenomatous polyp to invasive carcinoma is the degradation of the epithelial basement membrane. By the generation of plasmin, plasminogen activators may play an important role in regulating the extracellular protease activity required for this event to occur. The production of biofunctional urokinase and of tissue plasminogen activator was therefore investigated in the dimethylhydrazine induced rat model of colorectal neoplasia. Both adenomatous polyps (p values less than 0.001) and colorectal carcinomas (p values less than 0.001) were demonstrated to produce a significant excess of both urokinase and tissue plasminogen activator when compared with macroscopically normal colon. There was, however, no increased production of either enzyme by macroscopically normal preneoplastic colon when compared with control colon. This enhanced capacity of colorectal tumours to produce plasminogen activators and generate plasmin is thus a feature of both the premalignant as well as the malignant phenotype. These enzymes may contribute to the malignant potential of adenomatous polyps and to the invasive capacity of established carcinomas. PMID:3115868

  14. Translocations in epithelial cancers

    PubMed Central

    Chad Brenner, J.; Chinnaiyan, Arul M.

    2009-01-01

    Genomic translocations leading to the expression of chimeric transcripts characterize several hematologic, mesenchymal and epithelial malignancies. While several gene fusions have been linked to essential molecular events in hematologic malignancies, the identification and characterization of recurrent chimeric transcripts in epithelial cancers has been limited. However, the recent discovery of the recurrent gene fusions in prostate cancer has sparked a revitalization of the quest to identify novel rearrangements in epithelial malignancies. Here, the molecular mechanisms of gene fusions that drive several epithelial cancers and the recent technological advances that increase the speed and reliability of recurrent gene fusion discovery are explored. PMID:19406209

  15. Association between Cysticercosis and Neoplasia: A Study Based on Autopsy Findings

    PubMed Central

    Cavellani, Camila Lourencini; da Silva, Aline Cristina Souza; Ribeiro, Grace Kelly Naves de Aquino; Oliveira, Lívia Ferreira; Ferraz, Mara Lúcia Fonseca; Teixeira, Vicente de Paula Antunes

    2013-01-01

    Chronic infections including the cysticercosis induce inflammatory cells to produce free radicals and synthesize carcinogenic toxins. The cells with genetic mutations proliferate in a disorganized manner, leading to the development of neoplasia. The aim of the present study was to demonstrate the relation between cysticercosis and neoplasia. Patients autopsied were divided into 4 groups: patients with neoplasia and cysticercosis (NC), patients with neoplasia only (NN), patients with cysticercosis only (CC), and patients without neoplasia or cysticercosis (WW). Of 2012 autopsy reports analyzed, 0.4 showed NC. In groups CC and NC, the most common location of the parasite was the brain. There was a predominance of three or more cysticerci in groups NC and CC. In the NC group, all had malignant neoplasms, and was predominance of benign neoplasm in NN group. The digestive system was the most frequent neoplasia. By calculating odds ratio, rate of neoplasia in patients with cysticercosis was 0.74. In conclusion, the demographic profile of patients with cysticercosis and neoplasia is similar to that of patients with cysticercosis alone. The incidence of cysticercosis and neoplasia was greater in older patients suggesting that immunosenescence may contribute to development of neoplasia promoted by cysticercosis. PMID:24288510

  16. Homozygotes for the autosomal dominant neoplasia syndrome (MEN1)

    SciTech Connect

    Brandi, M.L.; Falchetti, A.; Tonelli, F. ); Weber, G.; Svensson, A.; Larsson, C. ); Castello, R.; Furlani, L.; Scappaticci, S.; Fraccaro, M.

    1993-12-01

    Families in which both parents are heterozygotes for the same autosomal dominant neoplasia syndrome are extremely unusual. Recently, the authors had the unique opportunity to evaluate three symptomatic siblings from the union between two unrelated individuals affected by multiple endocrine neoplasia type 1 (MEN1). When the three siblings and their parents and relatives were genotyped for 12 markers tightly linked to the MEN1 locus, at 11q13, two of the siblings were found to be homozygotes, and one a heterozygote, for MEN1. With regard to the MEN1 syndrome, no phenotypic differences were observed between the two homozygotes and the heterozygotes. However, the two homozygotes showed unexplained infertility, which was not the case for any of the heterozygotes. Thus, MEN1 appears to be a disease with complete dominance, and the presence of two MEN1 alleles with mutations of the type that occur constitutionally may be insufficient for tumor development. 28 refs., 2 figs.

  17. An inducible knockout mouse to model the cell-autonomous role of PTEN in initiating endometrial, prostate and thyroid neoplasias

    PubMed Central

    Mirantes, Cristina; Eritja, Núria; Dosil, Maria Alba; Santacana, Maria; Pallares, Judit; Gatius, Sónia; Bergadà, Laura; Maiques, Oscar; Matias-Guiu, Xavier; Dolcet, Xavier

    2013-01-01

    SUMMARY PTEN is one of the most frequently mutated tumor suppressor genes in human cancers. The role of PTEN in carcinogenesis has been validated by knockout mouse models. PTEN heterozygous mice develop neoplasms in multiple organs. Unfortunately, the embryonic lethality of biallelic excision of PTEN has inhibited the study of complete PTEN deletion in the development and progression of cancer. By crossing PTEN conditional knockout mice with transgenic mice expressing a tamoxifen-inducible Cre-ERT under the control of a chicken actin promoter, we have generated a tamoxifen-inducible mouse model that allows temporal control of PTEN deletion. Interestingly, administration of a single dose of tamoxifen resulted in PTEN deletion mainly in epithelial cells, but not in stromal, mesenchymal or hematopoietic cells. Using the mT/mG double-fluorescent Cre reporter mice, we demonstrate that epithelial-specific PTEN excision was caused by differential Cre activity among tissues and cells types. Tamoxifen-induced deletion of PTEN resulted in extremely rapid and consistent formation of endometrial in situ adenocarcinoma, prostate intraepithelial neoplasia and thyroid hyperplasia. We also analyzed the role of PTEN ablation in other epithelial cells, such as the tubular cells of the kidney, hepatocytes, colonic epithelial cells or bronchiolar epithelium, but those tissues did not exhibit neoplastic growth. Finally, to validate this model as a tool to assay the efficacy of anti-tumor drugs in PTEN deficiency, we administered the mTOR inhibitor everolimus to mice with induced PTEN deletion. Everolimus dramatically reduced the progression of endometrial proliferations and significantly reduced thyroid hyperplasia. This model could be a valuable tool to study the cell-autonomous mechanisms involved in PTEN-loss-induced carcinogenesis and provides a good platform to study the effect of anti-neoplastic drugs on PTEN-negative tumors. PMID:23471917

  18. The prevalence and characteristics of colorectal neoplasia in acromegaly.

    PubMed

    Renehan, A G; Bhaskar, P; Painter, J E; O'Dwyer, S T; Haboubi, N; Varma, J; Ball, S G; Shalet, S M

    2000-09-01

    An increased prevalence of colorectal neoplasia has been reported in acromegalic patients, and recommendations have been made for early colonoscopic screening and regular surveillance. This assumption, however, is frequently drawn from studies using selected control populations. To clarify colonoscopic management in these patients, we undertook a 2-center prospective screening colonoscopy study in 122 acromegalics (age range, 25-82 yr). In the absence of ideal age-matched controls, we calculated prevalence rates of occult adenocarcinomas and adenomas in the general population using cumulative data in the published literature from 8 autopsy studies (model 1, n = 3,559) and 4 screening colonoscopy studies (model 2, n= 810), applying linear regression models. Of the 115 patients with complete examinations, adenocarcinomas were discovered in 3 (2.6%), and at least 1 adenoma was found in 11, giving an overall prevalence of neoplasia of 12% (14 of 115). Prevalence rates for age bands 30-40, 40-49, 50-59, 60-69, and 70+ yr were 0%, 8%, 12%, 20%, and 21%, respectively. Compared with the 2 control models, the prevalence of occult colorectal cancer was not significantly increased (acromegalics vs. models 1 and 2, 2.6% vs. 2.3% and 0.9%), nor was there an increase in the prevalence of adenomas in any age band. Pathological characteristics showed some differences, in that adenomas in acromegalics tended to be right sided (68% vs. 57% and 56%), larger (for > or =10 mm, 27% vs. 13% and 9%), and of advanced histology (for tubulovillous, 27% vs. 4% and 22%). No associations were found between the presence of colonic neoplasia and the duration of disease, total GH exposure, cure status, and serum insulin-like growth factor I. This study has failed to demonstrate an increased prevalence of neoplasia in acromegalic patients compared with the expected prevalence in the general population and questions the need for an aggressive colonoscopic screening policy.

  19. Disruption of the Cdc42/Par6/aPKC or Dlg/Scrib/Lgl Polarity Complex Promotes Epithelial Proliferation via Overlapping Mechanisms.

    PubMed

    Schimizzi, Gregory V; Maher, Meghan T; Loza, Andrew J; Longmore, Gregory D

    2016-01-01

    The establishment and maintenance of apical-basal polarity is a defining characteristic and essential feature of functioning epithelia. Apical-basal polarity (ABP) proteins are also tumor suppressors that are targeted for disruption by oncogenic viruses and are commonly mutated in human carcinomas. Disruption of these ABP proteins is an early event in cancer development that results in increased proliferation and epithelial disorganization through means not fully characterized. Using the proliferating Drosophila melanogaster wing disc epithelium, we demonstrate that disruption of the junctional vs. basal polarity complexes results in increased epithelial proliferation via distinct downstream signaling pathways. Disruption of the basal polarity complex results in JNK-dependent proliferation, while disruption of the junctional complex primarily results in p38-dependent proliferation. Surprisingly, the Rho-Rok-Myosin contractility apparatus appears to play opposite roles in the regulation of the proliferative phenotype based on which polarity complex is disrupted. In contrast, non-autonomous Tumor Necrosis Factor (TNF) signaling appears to suppress the proliferation that results from apical-basal polarity disruption, regardless of which complex is disrupted. Finally we demonstrate that disruption of the junctional polarity complex activates JNK via the Rho-Rok-Myosin contractility apparatus independent of the cortical actin regulator, Moesin.

  20. Disruption of the Cdc42/Par6/aPKC or Dlg/Scrib/Lgl Polarity Complex Promotes Epithelial Proliferation via Overlapping Mechanisms

    PubMed Central

    Schimizzi, Gregory V.; Maher, Meghan T.; Loza, Andrew J.; Longmore, Gregory D.

    2016-01-01

    The establishment and maintenance of apical-basal polarity is a defining characteristic and essential feature of functioning epithelia. Apical-basal polarity (ABP) proteins are also tumor suppressors that are targeted for disruption by oncogenic viruses and are commonly mutated in human carcinomas. Disruption of these ABP proteins is an early event in cancer development that results in increased proliferation and epithelial disorganization through means not fully characterized. Using the proliferating Drosophila melanogaster wing disc epithelium, we demonstrate that disruption of the junctional vs. basal polarity complexes results in increased epithelial proliferation via distinct downstream signaling pathways. Disruption of the basal polarity complex results in JNK-dependent proliferation, while disruption of the junctional complex primarily results in p38-dependent proliferation. Surprisingly, the Rho-Rok-Myosin contractility apparatus appears to play opposite roles in the regulation of the proliferative phenotype based on which polarity complex is disrupted. In contrast, non-autonomous Tumor Necrosis Factor (TNF) signaling appears to suppress the proliferation that results from apical-basal polarity disruption, regardless of which complex is disrupted. Finally we demonstrate that disruption of the junctional polarity complex activates JNK via the Rho-Rok-Myosin contractility apparatus independent of the cortical actin regulator, Moesin. PMID:27454609

  1. Piroxicam decreases postirradiation colonic neoplasia in the rat

    SciTech Connect

    Northway, M.G.; Scobey, M.W.; Cassidy, K.T.; Geisinger, K.R. )

    1990-12-01

    This study evaluated the effects of the nonsteroidal antiinflammatory agent piroxicam on chronic radiation proctitis in the rat. Forty female Wistar rats received a 2250-cGy dose of irradiation to the distal 2 cm of the colon. Twenty received piroxicam 8.0 mg/kg orally 30 minutes before exposure and 24 hours after exposure; 20 rats served as irradiated controls. All animals were evaluated by colonoscopy 1 and 3 weeks postexposure and every third week until death or killing at 1 year. At killing, colons were removed for light microscopic examination. One year postirradiation results showed no differences in mortality, vascular changes, acute inflammation, colitis cystica profunda, or rectal stricture between the control and piroxicam-treated groups. However, at 1 year postirradiation the control group demonstrated neoplasia in 15 of 19 animals compared with eight of 20 animals in the piroxicam-treated group. The first endoscopic appearance of colonic neoplasm occurred at 15 weeks postirradiation in one control irradiated rat whereas the first evidence of endoscopic neoplasm in the piroxicam-treated group did not occur until 36 weeks postirradiation. Histologic examination documented a tendency toward a greater presence of adenocarcinomas in the control group compared with the piroxicam-treated group. The authors conclude that piroxicam treatment significantly decreased the incidence of colonic neoplasia in general as well as delayed the endoscopic appearance of colonic neoplasia in rats after pelvic irradiation. 41 references.

  2. Acetic acid chromoendoscopy: Improving neoplasia detection in Barrett's esophagus

    PubMed Central

    Chedgy, Fergus J Q; Subramaniam, Sharmila; Kandiah, Kesavan; Thayalasekaran, Sreedhari; Bhandari, Pradeep

    2016-01-01

    Barrett’s esophagus (BE) is an important condition given its significant premalignant potential and dismal five-year survival outcomes of advanced esophageal adenocarcinoma. It is therefore suggested that patients with a diagnosis of BE undergo regular surveillance in order to pick up dysplasia at an earlier stage to improve survival. Current “gold-standard” surveillance protocols suggest targeted biopsy of visible lesions followed by four quadrant random biopsies every 2 cm. However, this method of Barrett’s surveillance is fraught with poor endoscopist compliance as the procedures are time consuming and poorly tolerated by patients. There are also significant miss-rates with this technique for the detection of neoplasia as only 13% of early neoplastic lesions appear as visible nodules. Despite improvements in endoscope resolution these problems persist. Chromoendoscopy is an extremely useful adjunct to enhance mucosal visualization and characterization of Barrett’s mucosa. Acetic acid chromoendoscopy (AAC) is a simple, non-proprietary technique that can significantly improve neoplasia detection rates. This topic highlight summarizes the current evidence base behind AAC for the detection of neoplasia in BE and provides an insight into the direction of travel for further research in this area. PMID:27433088

  3. Activation of ras oncogenes preceding the onset of neoplasia

    SciTech Connect

    Kumar, R.; Barbacid, M. ); Sukumar, S. )

    1990-06-01

    The identification of ras oncogenes in human and animal cancers including precancerous lesions indicates that these genes participate in the early stages of neoplastic development. Yet, these observations do not define the timing of ras oncogene activation in the multistep process of carcinogenesis. To ascertain the timing of ras oncogene activation, an animal model system was devised that involves the induction of mammary carcinomas in rats exposed at birth to the carcinogen nitrosomethylurea. High-resolution restriction fragment length polymorphism analysis of polymerase chain reaction-amplified ras sequences revealed the presence of both H-ras and K-ras oncogenes in normal mammary glands 2 weeks after carcinogen treatment and at least 2 months before the onset of neoplasia. These ras oncogenes can remain latent within the mammary gland until exposure to estrogens, demonstrating that activation of ras oncogenes can precede the onset of neoplasia and suggesting that normal physiological proliferative processes such as estrogen-induced mammary gland development may lead to neoplasia if the targeted cells harbor latent ras oncogenes.

  4. Acetic acid chromoendoscopy: Improving neoplasia detection in Barrett's esophagus.

    PubMed

    Chedgy, Fergus J Q; Subramaniam, Sharmila; Kandiah, Kesavan; Thayalasekaran, Sreedhari; Bhandari, Pradeep

    2016-07-01

    Barrett's esophagus (BE) is an important condition given its significant premalignant potential and dismal five-year survival outcomes of advanced esophageal adenocarcinoma. It is therefore suggested that patients with a diagnosis of BE undergo regular surveillance in order to pick up dysplasia at an earlier stage to improve survival. Current "gold-standard" surveillance protocols suggest targeted biopsy of visible lesions followed by four quadrant random biopsies every 2 cm. However, this method of Barrett's surveillance is fraught with poor endoscopist compliance as the procedures are time consuming and poorly tolerated by patients. There are also significant miss-rates with this technique for the detection of neoplasia as only 13% of early neoplastic lesions appear as visible nodules. Despite improvements in endoscope resolution these problems persist. Chromoendoscopy is an extremely useful adjunct to enhance mucosal visualization and characterization of Barrett's mucosa. Acetic acid chromoendoscopy (AAC) is a simple, non-proprietary technique that can significantly improve neoplasia detection rates. This topic highlight summarizes the current evidence base behind AAC for the detection of neoplasia in BE and provides an insight into the direction of travel for further research in this area. PMID:27433088

  5. Slow progression of periampullary neoplasia in familial adenomatous polyposis.

    PubMed

    Moozar, Kouros L; Madlensky, Lisa; Berk, Terri; Gallinger, Steven

    2002-01-01

    Variable endoscopic surveillance protocols and treatment strategies have been proposed for periampullary neoplasia in familial adenomatous polyposis (FAP), primarily because of the lack of long-term, prospective natural history data. A total of 115 patients with FAP were followed prospectively for 10 years with periodic side-viewing upper gastrointestinal endoscopy by a single surgeon. The appearance of the duodenum was classified as stages 1 to 5. Statistical analysis included one-way analysis of variance for age comparisons between stage groupings and Kaplan-Meier analysis for the lifetime risks of having a particular stage of duodenal polyposis. Eighty-seven patients had multiple endoscopies over an average of 6.6 years. Thirty-three subjects had a change in stage, within an average time of 3.9 years at an average age of 41 years. The risk of having stage 3 or 4 duodenal neoplasia increased exponentially after the age of 40. The degree of dysplasia did not correlate with stage at initial classification. Progression of neoplasia in the duodenum of patients with FAP is slow. The severity of duodenal polyposis increases with age and is not influenced by the initial stage. The average time for progression of adenoma to carcinoma is likely long. PMID:12504221

  6. Development of a reactive stroma associated with prostatic intraepithelial neoplasia in EAF2 deficient mice.

    PubMed

    Pascal, Laura E; Ai, Junkui; Masoodi, Khalid Z; Wang, Yujuan; Wang, Dan; Eisermann, Kurtis; Rigatti, Lora H; O'Malley, Katherine J; Ma, Hei M; Wang, Xinhui; Dar, Javid A; Parwani, Anil V; Simons, Brian W; Ittman, Michael M; Li, Luyuan; Davies, Benjamin J; Wang, Zhou

    2013-01-01

    ELL-associated factor 2 (EAF2) is an androgen-responsive tumor suppressor frequently deleted in advanced prostate cancer that functions as a transcription elongation factor of RNA Pol II through interaction with the ELL family proteins. EAF2 knockout mice on a 129P2/OLA-C57BL/6J background developed late-onset lung adenocarcinoma, hepatocellular carcinoma, B-cell lymphoma and high-grade prostatic intraepithelial neoplasia. In order to further characterize the role of EAF2 in the development of prostatic defects, the effects of EAF2 loss were compared in different murine strains. In the current study, aged EAF2(-/-) mice on both the C57BL/6J and FVB/NJ backgrounds exhibited mPIN lesions as previously reported on a 129P2/OLA-C57BL/6J background. In contrast to the 129P2/OLA-C57BL/6J mixed genetic background, the mPIN lesions in C57BL/6J and FVB/NJ EAF2(-/-) mice were associated with stromal defects characteristic of a reactive stroma and a statistically significant increase in prostate microvessel density. Stromal inflammation and increased microvessel density was evident in EAF2-deficient mice on a pure C57BL/6J background at an early age and preceded the development of the histologic epithelial hyperplasia and neoplasia found in the prostates of older EAF2(-/-) animals. Mice deficient in EAF2 had an increased recovery rate and a decreased overall response to the effects of androgen deprivation. EAF2 expression in human cancer was significantly down-regulated and microvessel density was significantly increased compared to matched normal prostate tissue; furthermore EAF2 expression was negatively correlated with microvessel density. These results suggest that the EAF2 knockout mouse on the C57BL/6J and FVB/NJ genetic backgrounds provides a model of PIN lesions associated with an altered prostate microvasculature and reactive stromal compartment corresponding to that reported in human prostate tumors.

  7. Can photodynamic therapy be the preferred treatment option for anal intraepithelial neoplasia? Initial results of a pilot study.

    PubMed

    Welbourn, Hannah; Duthie, Graeme; Powell, John; Moghissi, Keyvan

    2014-03-01

    Anal intra-epithelial neoplasia (AIN) is a pre-malignant condition, which over time may progress to invasive anal squamous cell carcinoma. There is no standard treatment for AIN, but one of the therapeutic options available is photodynamic therapy (PDT). There are very few published studies of the efficacy of PDT, but it has been shown to produce downgrading of high-grade dysplasia in the anal region. The aim of the study was to evaluate the role of PDT in the treatment of AIN. Fifteen patients who received anal PDT between 2004 and 2013 were identified; twelve of these had AIN, two had intra-epithelial adenocarcinoma and one had dysplasia with high-risk human papillomavirus. After a median follow-up of nineteen months, ten of these have had at least one follow-up with aceto-white staining. Six of these ten patients had a complete response to PDT, although three subsequently had some recurrence. Three further patients had a partial response to PDT. There were no major therapeutic complications. Our findings suggest that PDT is a safe and feasible treatment option for AIN, associated with reasonable response rates and relatively little morbidity. Further research into the efficacy of PDT for AIN is required. PMID:24280437

  8. Squamous morules are functionally inert elements of premalignant endometrial neoplasia.

    PubMed

    Lin, Ming-Chieh; Lomo, Lesley; Baak, Jan P A; Eng, Charis; Ince, Tan A; Crum, Christopher P; Mutter, George L

    2009-02-01

    Squamous morules are a common component of premalignant glandular lesions that are followed by glandular, rather than squamous, carcinomas. We tested the hypothesis that the appearance of glands associated with morules predicts cancer risk, and undertook molecular testing to determine the clonal and hormonal response properties of admixed squamous and glandular elements. A total of 66 patients with squamous morules in an index endometrial biopsy had follow-up clinical data (average follow-up: interval 31 months, 2.5 biopsies) showing development of carcinoma in 11% (7/66) of cases. The histological appearance of morule-associated glands in the index biopsy was significantly associated with this clinical outcome, with the majority (71%, 5/7) of cancer occurrences following an overtly premalignant lesion (endometrial intraepithelial neoplasia) with squamous morules. Eight endometrial intraepithelial neoplasias with squamous morules were examined by immunohistochemistry for estrogen and progesterone receptors and mitotic activity (Ki-67 antigen percent stained). Glandular components had abundant estrogen and progesterone receptors, and high levels of mitotic activity in all cases. In sharp contrast, all squamous morules were devoid of sex hormone receptors and had undetectable or extremely low-proliferation rates. When mutated, the same specific PTEN mutation was detected in squamous and glandular elements, indicating that both are of common lineage. The clinical and laboratory data are consistent with a model of morule biology in which squamous morules are a hormonally incompetent subpopulation of endometrial glandular lesions. Isolated morules might result from artifactual displacement from their native glandular context, or selective hormonally induced regression of the glandular but not squamous components over time. Subsequent cancer risk, as promoted by estrogens, is greatest when the glandular component has the appearance of endometrial intraepithelial

  9. Squamous Morules Are Functionally Inert Elements of Premalignant Endometrial Neoplasia

    PubMed Central

    Lin, Ming-Chieh; Lomo, Lesley; Baak, Jan P. A.; Eng, Charis; Ince, Tan A.; Crum, Christopher P.; Mutter, George L.

    2008-01-01

    Squamous morules are a common component of premalignant glandular lesions that are followed by glandular, rather than squamous, carcinomas. We tested the hypothesis that the appearance of glands associated with morules predicts cancer risk, and undertook molecular testing to determine the clonal and hormonal response properties of admixed squamous and glandular elements. 66 patients with squamous morules in an index endometrial biopsy had followup clinical data (average followup: interval 31 months, 2.5 biopsies) showing development of carcinoma in 11% (7/66) of cases. The histological appearance of morule-associated glands in the index biopsy was significantly associated with this clinical outcome, with the majority (71%, 5/7) of cancer occurrences following an overtly premalignant lesion (Endometrial Intraepithelial Neoplasia) with squamous morules. Eight endometrial intraepithelial neoplasias with squamous morules were examined by immunohistochemistry for estrogen and progesterone receptors and mitotic activity (Ki-67 antigen percent stained). Glandular components had abundant estrogen and progesterone receptors, and high levels of mitotic activity in all cases. In sharp contrast, all squamous morules were devoid of sex hormone receptors and had undetectable or extremely low proliferation rates. When mutated, the same specific PTEN mutation was detected in squamous and glandular elements, indicating that both are of common lineage. The clinical and laboratory data are consistent with a model of morule biology in which squamous morules are a hormonally incompetent subpopulation of endometrial glandular lesions. Isolated morules might result from artifactual displacement from their native glandular context, or selective hormonally induced regression of the glandular but not squamous components over time. Subsequent cancer risk, as promoted by estrogens, is greatest when the glandular component has the appearance of endometrial intraepithelial neoplasia. Even

  10. [Anesthesiologic peculiarities in bilateral pheochromocytoma and suspected multiple endocrine neoplasia].

    PubMed

    Hack, G; Mihanovic, N; Helpap, B

    1985-10-01

    Based on a case report with surgical removal of bilateral giant phaeochromocytomas with heredofamilial affliction and suspicion of multiple endocrine neoplasia type II (MEN-II syndrome) and of malignancy, the anaesthetic implications are discussed in a patient inadvertently not prepared by antiadrenergic treatment. It is pointed out that in MEN II syndrome, a combination of phaeochromocytoma and medullary carcinoma of the thyroid, surgical removal of the phaeochromocytoma merits utmost priority before thyreoidectomy. The most important laboratory parameters in the diagnosis of MEN II syndrome are pre- and postoperative determinations of calcitonin and carcinoembryonal antigen (CEA).

  11. Integumentary Disorders Including Cutaneous Neoplasia in Older Horses.

    PubMed

    Knottenbelt, Derek C

    2016-08-01

    Few skin diseases specifically or exclusively affect older horses and donkeys. Hypertrichosis (hirsutism) associated with pituitary pars intermedia dysfunction is probably the most recognized and best understood exception and is the most common age-related skin condition in equids. Many other conditions are known to be more serious in older horses. Horses affected with immune-compromising conditions can be more severely affected by infectious diseases of the skin or heavy and pathologically significant parasitism. Neoplasia of the skin is probably more prevalent and worse in older horses, although many of the more serious skin tumors develop initially at a younger age. PMID:27329491

  12. [New challenges to the treatment of cervical intraepithelial neoplasia].

    PubMed

    Sun, J H

    2016-07-01

    Due to the progress of intracavitary afterloading technology and dosage of brachytherapy, a similar dose distribution as that of cervical conization can be achieved and can be applied to the treatment of cervical intraepithelial neoplasia (CIN), it is called "afterloading conization" . Being adjusted the radioactive source movement and weight, low exposure doses to the ovary, endometrium and vagina can be assured. So a high quality of life after treatment could be maintained and overcomes the shortcomings of cervical conization and hysterectomy, such as anesthesia, bleeding, over or insufficient treatment, early ovarian ageing and operative complications. PMID:27531273

  13. Endoscopic submucosal dissection for early Barrett’s neoplasia

    PubMed Central

    Barret, Maximilien; Cao, Dalhia Thao; Beuvon, Frédéric; Leblanc, Sarah; Terris, Benoit; Camus, Marine; Coriat, Romain; Chaussade, Stanislas

    2015-01-01

    Introduction The possible benefit of endoscopic submucosal dissection (ESD) for early neoplasia arising in Barrett’s esophagus remains controversial. We aimed to assess the efficacy and safety of ESD for the treatment of early Barrett’s neoplasia. Methods All consecutive patients undergoing ESD for the resection of a visible lesion in a Barrett’s esophagus, either suspicious of submucosal infiltration or exceeding 10 mm in size, between February 2012 and January 2015 were prospectively included. The primary endpoint was the rate of curative resection of carcinoma, defined as histologically complete resection of adenocarcinomas without poor histoprognostic factors. Results Thirty-five patients (36 lesions) with a mean age of 66.2 ± 12 years, a mean ASA score of 2.1 ± 0.7, and a mean C4M6 Barrett’s segment were included. The mean procedure time was 191 ± 79 mn, and the mean size of the resected specimen was 51.3 ± 23 mm. En bloc resection rate was 89%. Lesions were 12 ± 15 mm in size, and 81% (29/36) were invasive adenocarcinomas, six of which with submucosal invasion. Although R0 resection of carcinoma was 72.4%, the curative resection rate was 66% (19/29). After a mean follow-up of 12.9 ± 9 months, 16 (45.7%) patients had required additional treatment, among whom nine underwent surgical resection, and seven further endoscopic treatments. Metachronous lesions or recurrence of cancer developed during the follow-up period in 17.2% of the patients. The overall complication rate was 16.7%, including 8.3% perforations, all conservatively managed, and no bleeding. The 30-day mortality was 0%. Conclusion In this early experience, ESD yielded a moderate curative resection rate in Barrett’s neoplasia. At present, improvements are needed if ESD is to replace piecemeal endoscopic mucosal resection in the management of Barrett’s neoplasia. PMID:27087948

  14. The plasticity of human breast carcinoma cells is more than epithelial to mesenchymal conversion

    SciTech Connect

    Petersen, Ole William; Nielsen, Helga Lind; Gudjonsson, Thorarinn; Villadsen, René; Ronnov-Jessen, Lone; Bissell, Mina J.

    2001-05-12

    The human breast comprises three lineages: the luminal epithelial lineage, the myoepithelial lineage, and the mesenchymal lineage. It has been widely accepted that human breast neoplasia pertains only to the luminal epithelial lineage. In recent years, however, evidence has accumulated that neoplastic breast epithelial cells may be substantially more plastic in their differentiation repertoire than previously anticipated. Thus, along with an increasing availability of markers for the myoepithelial lineage, at least a partial differentiation towards this lineage is being revealed frequently. It has also become clear that conversions towards the mesenchymal lineage actually occur, referred to as epithelial to mesenchymal transitions. Indeed, some of the so-called myofibroblasts surrounding the tumor may indeed have an epithelial origin rather than a mesenchymal origin. Because myoepithelial cells, epithelial to mesenchymal transition-derived cells, genuine stromal cells and myofibroblasts share common markers, we now need to define a more ambitious set of markers to distinguish these cell types in the microenvironment of the tumors. This is necessary because the different microenvironments may confer different clinical outcomes. The aim of this commentary is to describe some of the inherent complexities in defining cellular phenotypes in the microenvironment of breast cancer and to expand wherever possible on the implications for tumor suppression and progression.

  15. The Role of MicroRNAs in Myeloproliferative Neoplasia.

    PubMed

    Alizadeh, Shaban; Azizi, Seyed Ghader; Soleimani, Masoud; Farshi, Yadollah; Kashani Khatib, Zahra

    2016-07-01

    MiRs are 17-25 nucleotide non-coding RNAs. These RNAs target approximately 80% of protein coding mRNAs. MiRs control gene expression and altered expression of them affects the development of cancer. MiRs can function as tumor suppressor via down-regulation of proto-oncogenes and may function as oncogenes by suppressing tumor suppressors. Myeloproliferative neoplasias (formerly known as chronic myeloproliferative disorders) form a class of hematologic malignancies demonstrating the expansion of stem cells in one or more hematopoietic cell lines. CML results from an acquired translocation known as BCR-ABL (Philadelphia chromosome). JAK2V617F mutation is present in over 95% of PV, 55% of ET and 65% of PMF cases. Aberrant expression of miR is associated with myeloproliferative neoplasias, pathogenesis, disease progress and response to treatment. MiRs can also be potential therapeutic targets. CML is mainly treated by tyrosine kinase inhibitors such as Imatinib. In addition, altered function of miRs may be used as a prognostic factor in treatment. Resistance to Imatinib is currently a major clinical problem. The role of a number of miRs has been demonstrated in this resistance. Changing expression pattern of miRs can be effective in response to treatment and inhibition of drug resistance. In this paper, we set out to evaluate the effect of miRs in pathogenesis and treatment of MPN. PMID:27489593

  16. Analysis of digitized cervical images to detect cervical neoplasia

    NASA Astrophysics Data System (ADS)

    Ferris, Daron G.

    2004-05-01

    Cervical cancer is the second most common malignancy in women worldwide. If diagnosed in the premalignant stage, cure is invariably assured. Although the Papanicolaou (Pap) smear has significantly reduced the incidence of cervical cancer where implemented, the test is only moderately sensitive, highly subjective and skilled-labor intensive. Newer optical screening tests (cervicography, direct visual inspection and speculoscopy), including fluorescent and reflective spectroscopy, are fraught with certain weaknesses. Yet, the integration of optical probes for the detection and discrimination of cervical neoplasia with automated image analysis methods may provide an effective screening tool for early detection of cervical cancer, particularly in resource poor nations. Investigative studies are needed to validate the potential for automated classification and recognition algorithms. By applying image analysis techniques for registration, segmentation, pattern recognition, and classification, cervical neoplasia may be reliably discriminated from normal epithelium. The National Cancer Institute (NCI), in cooperation with the National Library of Medicine (NLM), has embarked on a program to begin this and other similar investigative studies.

  17. The Role of MicroRNAs in Myeloproliferative Neoplasia

    PubMed Central

    Alizadeh, Shaban; Azizi, Seyed Ghader; Soleimani, Masoud; Farshi, Yadollah; Kashani Khatib, Zahra

    2016-01-01

    MiRs are 17-25 nucleotide non-coding RNAs. These RNAs target approximately 80% of protein coding mRNAs. MiRs control gene expression and altered expression of them affects the development of cancer. MiRs can function as tumor suppressor via down-regulation of proto-oncogenes and may function as oncogenes by suppressing tumor suppressors. Myeloproliferative neoplasias (formerly known as chronic myeloproliferative disorders) form a class of hematologic malignancies demonstrating the expansion of stem cells in one or more hematopoietic cell lines. CML results from an acquired translocation known as BCR-ABL (Philadelphia chromosome). JAK2V617F mutation is present in over 95% of PV, 55% of ET and 65% of PMF cases. Aberrant expression of miR is associated with myeloproliferative neoplasias, pathogenesis, disease progress and response to treatment. MiRs can also be potential therapeutic targets. CML is mainly treated by tyrosine kinase inhibitors such as Imatinib. In addition, altered function of miRs may be used as a prognostic factor in treatment. Resistance to Imatinib is currently a major clinical problem. The role of a number of miRs has been demonstrated in this resistance. Changing expression pattern of miRs can be effective in response to treatment and inhibition of drug resistance. In this paper, we set out to evaluate the effect of miRs in pathogenesis and treatment of MPN. PMID:27489593

  18. The c-Jun N-terminal kinase signaling pathway mediates chrysotile asbestos-induced alveolar epithelial cell apoptosis

    PubMed Central

    LI, PENG; LIU, TIE; KAMP, DAVID W.; LIN, ZIYING; WANG, YAHONG; LI, DONGHONG; YANG, LAWEI; HE, HUIJUAN; LIU, GANG

    2015-01-01

    Exposure to chrysotile asbestos exposure is associated with an increased risk of mortality in combination with pulmonary diseases including lung cancer, mesothelioma and asbestosis. Multiple mechanisms by which chrysotile asbestos fibers induce pulmonary disease have been identified, however the role of apoptosis in human lung alveolar epithelial cells (AEC) has not yet been fully explored. Accumulating evidence implicates AEC apoptosis as a crucial event in the development of both idiopathic pulmonary fibrosis and asbestosis. The aim of the present study was to determine whether chrysotile asbestos induces mitochondria-regulated (intrinsic) AEC apoptosis and, if so, whether this induction occurs via the activation of mitogen-activated protein kinases (MAPK). Human A549 bronchoalveolar carcinoma-derived cells with alveolar epithelial type II-like features were used. The present study showed that chrysotile asbestos induced a dose- and time-dependent decrease in A549 cell viability, which was accompanied by the activation of the MAPK c-Jun N-terminal kinases (JNK), but not the MAPKs extracellular signal-regulated kinase 1/2 and p38. Chrysotile asbestos was also shown to induce intrinsic AEC apoptosis, as evidenced by the upregulation of the pro-apoptotic genes Bax and Bak, alongside the activation of caspase-9, poly (ADP-ribose) polymerase (PARP), and the release of cytochrome c. Furthermore, the specific JNK inhibitor SP600125 blocked chrysotile asbestos-induced JNK activation and subsequent apoptosis, as assessed by both caspase-9 cleavage and PARP activation. The results of the present study demonstrated that chrysotile asbestos induces intrinsic AEC apoptosis by a JNK-dependent mechanism, and suggests a potential novel target for the modulation of chrysotile asbestos-associated lung diseases. PMID:25530474

  19. Radiogenic neoplasia in thyroid and mammary clonogens. Progress report, January 1, 1990--December 31, 1992

    SciTech Connect

    Clifton, K.H.

    1992-05-20

    We have developed rat thyroid and mammary clonogen transplantation systems for the study of radiogenic cancer induction at the target cell level in vivo. The epithelial cell populations of both glands contain small subpopulations of cells which are capable of giving rise to monoclonal glandular structures when transplanted and stimulated with appropriate hormones. Previous results indicated that these clonogens are the precursor cells of radiogenic cancer, and that initiation, is common event at the clonegenic cell level. Detailed information on the physiologic control of clonogen proliferation, differentiation, and total numbers is thus essential to an understanding of the carcinogenic process. We report here studies on investigations on the relationships between grafted thyroid cell number and the rapidity and degree of reestablishment of the thyroid-hypothalamus-pituitary feedback axis in thyroidectomized rats maintained on a normal diet or an iodine deficient diet; studies of the persistence of, and the differentiation potential and functional characteristics of, the TSH-(thyrotropin-) responsive sub- population of clonogens during goitrogenesis, the plateau-phase of goiter growth, and goiter involution; studies of changes in the size of the clonogen sub-population during goitrogenesis, goiter involution and the response to goitrogen rechallenge; and a large carcinogenesis experiment on the nature of the grafted thyroid cell number-dependent suppression of promotion/progression to neoplasia in grafts of radiation-initiated thyroid cells. Data from these studies will be used in the design of future carcinogenesis experiments on neoplastic initiation by high and low LET radiations and on cell interactions during the neoplastic process.

  20. Influence of demographic parameters on rectal epithelial proliferation.

    PubMed

    Fireman, Z; Rozen, P; Fine, N; Chetrit, A

    1989-09-15

    Measurement of rectal epithelial proliferation is now being used as a biomarker for assessing risk for colorectal cancer and response within dietary intervention studies. We examined the possible confounding effects of demographic parameters on the proliferation of 52 healthy middle-aged volunteers without known risk factors for colorectal cancer. No significant effects on proliferation of age, sex or ethnic grouping were found other than marked urban-rural differences amongst men. We hypothesise that these could be explained by differences in dietary habits and their deleterious effects in the older male population. Careful matching of controls are probably needed in order to demonstrate the minor changes in mucosal proliferation that could reflect risk for neoplasia. Further human studies are needed to examine the effects of diet and extremes of age on proliferation.

  1. Microtopographic Inspection and Fractal Analysis of Skin Neoplasia

    NASA Astrophysics Data System (ADS)

    Costa, Manuel F. M.; Hipolito, Alberto Valencia; Gutierrez, Gustavo Fidel; Chanona, Jorge; Gallegos, Eva Ramón

    2008-04-01

    ) corresponding to some neoplasia is higher (1.334+/-0.072) than those for healthy skin (1.091+/-0.082). A significant difference between the fractal dimensions of neoplasia and healhty skin (>0.001) was registered. The FD of microtopography maps (FDm) can also distinguish between healthy and malignant tissue in general (2.277+/-0.070 to 2.309+/-0.040), but not discriminate the different types of skin neoplasias. The combination of the rugometric evaluation and fractal geometry characterization provides valuable information about the malignity of skin lesions and type of lesion.

  2. Bovine myocardial epithelial inclusions.

    PubMed

    Baker, D C; Schmidt, S P; Langheinrich, K A; Cannon, L; Smart, R A

    1993-01-01

    Light microscopic, histochemical, immunohistochemical, and ultrastructural methods were used to examine myocardial epithelial masses in the hearts of ten cattle. The tissues consisted of paraffin-embedded or formalin-fixed samples from eight hearts that were being inspected in slaughter houses and from two hearts from calves that died of septicemia. The ages of the cattle ranged from 4 days to 12 years; the breeds were unspecified for all but one Hereford female and the two Holstein calves; and there were three males, four females, and three steers. The masses in these cases were compared with similar appearing lesions found in other animal species. The lesions in the bovine hearts were single to multiple, well circumscribed, found in the left ventricle wall, and composed of squamous to cuboidal epithelial cells that formed tubular, ductular, and acinar structures with lumens that were void or filled with amorphous protein globules. Electron microscopic examination revealed epithelial cells that had sparse apical microvilli, tight apical intercellular junctions, perinuclear bundles of filaments, and rare cilia. Almost half of the bovine epithelial masses (4/9) had occasional diastase-resistant periodic acid-Schiff-positive granules in their cytoplasm, and few had hyaluronidase-resistant alcian blue-positive granules (2/9) or colloidal iron-positive granules (1/9). All myocardial masses had abundant collagen surrounding the tubular and acinar structures, and 2/9 had elastin fibers as well. None of the myocardial masses had Churukian-Schenk or Fontana Masson's silver staining granules in epithelial cells. Immunohistochemically, all bovine myocardial tumors stained positively for cytokeratin (8/8), and occasional masses stained positively for vimentin (3/8) or carcinoembryonic antigen (3/8). None of the masses stained positively for desmin. The myocardial epithelial tumors most likely represent endodermal rests of tissue misplaced during organogenesis.

  3. The riddle of hepatic neoplasia in brown bullheads from relatively unpolluted waters in New York State.

    PubMed

    Spitsbergen, J M; Wolfe, M J

    1995-01-01

    Since 1985, pathologists at Cornell University have investigated the causes of lesions in freshwater fish throughout New York waters in order to clarify possible impairment of fish health by environmental contaminants. Fishermen and biologists alerted us to several relatively protected reservoirs and ponds in which we have found no evidence of elevated levels of anthropogenic environmental contaminants but in which up to 100% of brown bullheads exhibited skin neoplasia. Complete necropsies and histologic study revealed that over 30% of mature brown bullheads from some of these sites had benign or malignant hepatocellular or biliary liver neoplasia. Up to 50% of brown bullheads had benign or malignant liver neoplasia in other relatively unpolluted waters with no evidence of skin neoplasia in bullheads. Multiple samplings of brown bullheads from several of these sites have revealed puzzling variability in the prevalence of skin, liver, and other neoplasia in these fish populations. The cause of these striking epizootics of neoplasia in brown bullheads in unpolluted waters in New York State remains unclear. We hypothesize that natural carcinogens such as N-nitroso compounds formed in aquatic sediments or radon from geologic formations may contribute to epizootic fish neoplasia in New York waters. PMID:8772257

  4. Myeloid Neoplasias: What Molecular Analyses Are Telling Us

    PubMed Central

    Gutiyama, Luciana M.; Coutinho, Diego F.; Lipkin, Marina V.; Zalcberg, Ilana R.

    2012-01-01

    In the last decades, cytogenetic and molecular characterizations of hematological disorders at diagnosis and followup have been most valuable for guiding therapeutic decisions and prognosis. Genetic and epigenetic alterations detected by different procedures have been associated to different cancer types and are considered important indicators for disease classification, differential diagnosis, prognosis, response, and individualization of therapy. The search for new biomarkers has been revolutionized by high-throughput technologies. At this point, it seems that we have overcome technological barriers, but we are still far from sorting the biological puzzle. Evidence based on translational research is required for validating novel genetic and epigenetic markers for routine clinical practice. We herein discuss the importance of genetic abnormalities and their molecular pathways in acute myeloid leukemia, myelodysplastic syndromes, and myeloproliferative neoplasms. We also discuss how novel genomic abnormalities may interact and reassess concepts and classifications of myeloid neoplasias. PMID:23056961

  5. Atypical clinical manifestations of multiple endocrine neoplasia type 1 syndrome.

    PubMed

    Krysiak, Robert; Kajdaniuk, Dariusz; Marek, Bogdan; Okopień, Bogusław

    2009-03-01

    Multiple endocrine neoplasia type 1 (MEN1) is a hereditary tumor syndrome characterized by a genetic predisposition to develop a variety of neuroendocrine tumors and hormone excess syndromes. The major components of MEN1 are hyperparathyroidism due to multiple parathyroid adenomas or hyperplasia, duodenopancreatic neuroendocrine tumors and pituitary adenomas, most often producing prolactin. Physicians' inadequate knowledge of this clinical entity and sometimes its atypical presentation result in a probable significant underdiagnosis of MEN1. This describes the case of a 65-year-old female in whom primary hyperparathyroidism, limited to only one parathyroid gland, was preceded by acromegaly that was diagnosed 23 years earlier. This case shows that MEN1 manifests itself even in older groups and hyperparathyroidism may not be the first symptom of this syndrome. Therefore, we believe that all subjects who, regardless of age, gender and initial manifestation present with whichever the major symptom should be followed up regularly for the early detection of MEN1. PMID:19514648

  6. Gallbladder Papillary Neoplasia Associated With Intrahepatic Carcinoma and Pancreaticobiliary Malformation

    PubMed Central

    Resende, Vivian; Roda, Rodrigo; Pedrosa, Moises Salgado

    2012-01-01

    Papillary carcinoma is a rare tumor of the gallbladder. Papillary mucinous lesions of the intra- and extra-hepatic biliary tract (BT- IPMN) have been recognized. However the gallbladder is not included, except for the diffuse papillomatosis, where the sequence biliary papillomatosis to papillary carcinoma is proposed. We report a simultaneous case of gallbladder papillary neoplasia and intrahepatic duct carcinoma in situ associated with pancreaticobiliary maljunction (PBM). We proposed that double location, in our case, is more likely explained by a diffuse biliopancreatic tree disease leading to synchronous tumors arising in amenable duct. It was verified absence of continuity between gallbladder and intrahepatic bile duct site of involvement, absence of lymph node metastasis or venous involvement. This case report supports the concept of a proliferative and neoplastic process involving simultaneously the biliary tree and gallbladder associated with PBM.

  7. Thyroid neoplasia following radiation therapy for Hodgkin's lymphoma

    SciTech Connect

    McHenry, C.; Jarosz, H.; Calandra, D.; McCall, A.; Lawrence, A.M.; Paloyan, E.

    1987-06-01

    The question of thyroid neoplasia following high-dose radiation treatment to the neck and mediastinum for malignant neoplasms such as Hodgkin's lymphoma in children and young adults has been raised recently. Five patients, 19 to 39 years old, were operated on for thyroid neoplasms that developed following cervical and mediastinal radiation therapy for Hodgkin's lymphoma. Three patients had papillary carcinomas and two had follicular adenomas. The latency period between radiation exposure and the diagnosis of thyroid neoplasm ranged from eight to 16 years. This limited series provided strong support for the recommendation that children and young adults who are to receive high-dose radiation therapy to the head, neck, and mediastinum should receive suppressive doses of thyroxine prior to radiation therapy in order to suppress thyrotropin (thyroid-stimulating hormone) and then be maintained on a regimen of suppression permanently.

  8. Is bacterial vaginosis associated with cervical intraepithelial neoplasia?

    PubMed

    Boyle, D C M; Barton, S E; Uthayakumar, S; Hay, P E; Pollock, J W; Steer, P J; Smith, J R

    2003-01-01

    Previous research has produced conflicting results regarding the association of bacterial vaginosis (BV) and cervical intraepithelial neoplasia (CIN). These studies have been weakened in their conclusions mainly by failure to adequately control for the presence of sexually transmitted infections (STIs). One proposed mechanism suggesting that carcinogenic nitrosamines acting either independently or via human papilloma virus (HPV) has not been fully tested previously. We undertook a prospective, case-controlled, cross-sectional study where the presence of STIs, in particular human papillomavirus (HPV) which is known to be associated with the development of CIN, was controlled for. Women with BV were not found to have CIN more frequently than women with normal vaginal flora and the quantities of nitrosamines produced by women with BV did not differ significantly from women without BV. We thus found that BV is not associated with CIN. PMID:12657117

  9. A Metastatic Ovarian Angiosarcoma Mimicking Hematologic Neoplasia at Diagnosis

    PubMed Central

    Gaiolla, Rafael Dezen; Duarte, Ívison Xavier; Bacchi, Carlos Eduardo; Paiva, Carlos Eduardo

    2014-01-01

    Angiosarcomas are rare aggressive neoplasms of vascular endothelial origin with a high metastatic rate and poor prognosis. Involvement of the bone marrow by the angiosarcoma is exceedingly uncommon, and there have only been a few cases reported in the literature to date. Clinical manifestations and common laboratory findings of bone marrow involvement can mimic other more common bone marrow-replacing neoplasias such as lymphomas and acute leukemia. A definitive diagnosis is difficult to make from cytologic material, probably due to an associated bone marrow fibrosis, and requires bone marrow trephine biopsy with an immunohistochemical profile. Here we had the opportunity to study a case of metastatic angiosarcoma with positive cytologic findings and an unusual presentation that challenged its primary diagnosis. PMID:24847252

  10. Photodynamic therapy of Cervical Intraepithelial Neoplasia (CIN) high grade

    NASA Astrophysics Data System (ADS)

    Carbinatto, Fernanda M.; Inada, Natalia M.; Lombardi, Welington; da Silva, Eduardo V.; Belotto, Renata; Kurachi, Cristina; Bagnato, Vanderlei S.

    2016-02-01

    Cervical intraepithelial neoplasia (CIN) is the precursor of invasive cervical cancer and associated with human papillomavirus (HPV) infection. Photodynamic therapy (PDT) is a technique that has been used for the treatment of tumors. PDT is based on the accumulation of a photosensitizer in target cells that will generate cytotoxic reactive oxygen species upon illumination, inducing the death of abnormal tissue and PDT with less damaging to normal tissues than surgery, radiation, or chemotherapy and seems to be a promising alternative procedure for CIN treatment. The CIN high grades (II and III) presents potential indications for PDT due the success of PDT for CIN low grade treatment. The patients with CIN high grade that were treated with new clinic protocol shows lesion regression to CIN low grade 60 days after the treatment. The new clinical protocol using for treatment of CIN high grade shows great potential to become a public health technique.

  11. Anterior Segment Imaging in Ocular Surface Squamous Neoplasia

    PubMed Central

    Vora, Gargi K.

    2016-01-01

    Recent advances in anterior segment imaging have transformed the way ocular surface squamous neoplasia (OSSN) is diagnosed and monitored. Ultrasound biomicroscopy (UBM) has been reported to be useful primarily in the assessment of intraocular invasion and metastasis. In vivo confocal microscopy (IVCM) shows enlarged and irregular nuclei with hyperreflective cells in OSSN lesions and this has been found to correlate with histopathology findings. Anterior segment optical coherence tomography (AS-OCT) demonstrates thickened hyperreflective epithelium with an abrupt transition between abnormal and normal epithelium in OSSN lesions and this has also been shown to mimic histopathology findings. Although there are limitations to each of these imaging modalities, they can be useful adjunctive tools in the diagnosis of OSSN and could greatly assist the clinician in the management of OSSN patients. Nevertheless, anterior segment imaging has not replaced histopathology's role as the gold standard in confirming diagnosis. PMID:27800176

  12. Uterine arteriovenous malformations following gestational trophoblastic neoplasia: a systematic review.

    PubMed

    Touhami, Omar; Gregoire, Jean; Noel, Patricia; Trinh, Xuan Bich; Plante, Marie

    2014-10-01

    Uterine arteriovenous malformation (AVM) following gestational trophoblastic neoplasia (GTN) is a rare condition. It can be associated with chronic vaginal bleeding or life-threatening heavy bleeding, even after complete resolution of the tumor following chemotherapy. This analysis aimed to perform an extensive systematic review highlighting clinical symptoms, imaging, management and prognosis of this rare complication of GTN. We also describe an additional case of uterine AVM following GTN. We conducted a literature search using Medline, Embase and Cochrane library to analyze the clinical data of 49 published cases of uterine AVM following GTN. Median age of the women diagnosed with AVM was 29 years (range 15-49). Median gravidity was 2 (range 1-8) and 50% of women were nulligravida. Complete molar pregnancy was the most common initial gestational trophoblastic diagnosis (48%). Overall, 44 patients (88%) were symptomatic and presented with chronic or acute abnormal vaginal bleeding. Only 3 patients had an undetectable HCG level at the time of uterine AVM diagnosis. Hypo-echoic space in the myometrium is the most relevant finding on ultrasonography but the gold standard for the definitive diagnosis of AVMs is angiographic examination. Uterine artery embolization was the most common treatment option performed in 82% of the patients and was successful in controlling the bleeding in 85% of cases. We identified 20 pregnancies after successful embolization of uterine AVM following a GTN and 90% of them were successful. Because of the risk of life-threatening heavy bleeding, the diagnosis of uterine AVM should always be considered in patients with a history of recurrent unexplained vaginal bleeding after gestational trophoblastic neoplasia. Angiographic embolization is successful in the majority of cases and does not appear to compromise future pregnancy.

  13. Advanced colorectal neoplasia risk stratification by penalized logistic regression.

    PubMed

    Lin, Yunzhi; Yu, Menggang; Wang, Sijian; Chappell, Richard; Imperiale, Thomas F

    2016-08-01

    Colorectal cancer is the second leading cause of death from cancer in the United States. To facilitate the efficiency of colorectal cancer screening, there is a need to stratify risk for colorectal cancer among the 90% of US residents who are considered "average risk." In this article, we investigate such risk stratification rules for advanced colorectal neoplasia (colorectal cancer and advanced, precancerous polyps). We use a recently completed large cohort study of subjects who underwent a first screening colonoscopy. Logistic regression models have been used in the literature to estimate the risk of advanced colorectal neoplasia based on quantifiable risk factors. However, logistic regression may be prone to overfitting and instability in variable selection. Since most of the risk factors in our study have several categories, it was tempting to collapse these categories into fewer risk groups. We propose a penalized logistic regression method that automatically and simultaneously selects variables, groups categories, and estimates their coefficients by penalizing the [Formula: see text]-norm of both the coefficients and their differences. Hence, it encourages sparsity in the categories, i.e. grouping of the categories, and sparsity in the variables, i.e. variable selection. We apply the penalized logistic regression method to our data. The important variables are selected, with close categories simultaneously grouped, by penalized regression models with and without the interactions terms. The models are validated with 10-fold cross-validation. The receiver operating characteristic curves of the penalized regression models dominate the receiver operating characteristic curve of naive logistic regressions, indicating a superior discriminative performance.

  14. Epithelial atypia in biopsies performed for microcalcifications. Practical considerations about 2,833 serially sectioned surgical biopsies with a long follow-up

    PubMed Central

    MacGrogan, Gaëtan; Mathoulin-Pélissier, Simone; Vincent-Salomon, Anne; Soubeyran, Isabelle; Picot, Véronique; Coindre, Jean-Michel; Mauriac, Louis

    2007-01-01

    This study analyzes the occurrence of epithelial atypia in 2,833 serially sectioned surgical breast biopsies (SB) performed for microcalcifications (median number of blocks per SB:26) and the occurrence of subsequent cancer after an initial diagnosis of epithelial atypia (median follow-up 160 months). Epithelial atypia (flat epithelial atypia, atypical ductal hyperplasia, and lobular neoplasia) were found in 971 SB, with and without a concomitant cancer in 301 (31%) and 670 (69%) SB, respectively. Thus, isolated epithelial atypia were found in 670 out of the 2,833 SB (23%). Concomitant cancers corresponded to ductal carcinomas in situ and micro-invasive (77%), invasive ductal carcinomas not otherwise specified (15%), invasive lobular carcinomas (4%), and tubular carcinomas (4%). Fifteen out of the 443 patients with isolated epithelial atypia developed a subsequent ipsilateral (n = 14) and contralateral (n = 1) invasive cancer. The high slide rating might explain the high percentages of epithelial atypia and concomitant cancers and the low percentage of subsequent cancer after a diagnosis of epithelial atypia as a single lesion. Epithelial atypia could be more a risk marker of concomitant than subsequent cancer. PMID:17551752

  15. Malignant Neoplasia of the Sex Skin in 2 Chimpanzees (Pan troglodytes)

    PubMed Central

    Beck, Amanda P; Magden, Elizabeth R; Buchl, Stephanie J; Baze, Wallace B

    2016-01-01

    This report describes 2 cases of spontaneous malignant neoplasia within the sex skin of aged female chimpanzees. In both cases, the initial presentation resembled nonhealing traumatic wounds to the sex skin, with different degrees of infection, ulceration, and tissue necrosis. Histopathology of the lesions confirmed the diagnosis of squamous cell carcinoma in one case and of adenocarcinoma with metastasis in the other. Advanced age and previous trauma likely contributed to the development of the neoplasias in both cases; long-term sun exposure may also have contributed to the development of the squamous cell carcinoma. To our knowledge, these 2 cases represent the first reports of sex skin neoplasia in chimpanzees. PMID:27053571

  16. Malignant Neoplasia of the Sex Skin in 2 Chimpanzees (Pan troglodytes).

    PubMed

    Beck, Amanda P; Magden, Elizabeth R; Buchl, Stephanie J; Baze, Wallace B

    2016-04-01

    This report describes 2 cases of spontaneous malignant neoplasia within the sex skin of aged female chimpanzees. In both cases, the initial presentation resembled nonhealing traumatic wounds to the sex skin, with different degrees of infection, ulceration, and tissue necrosis. Histopathology of the lesions confirmed the diagnosis of squamous cell carcinoma in one case and of adenocarcinoma with metastasis in the other. Advanced age and previous trauma likely contributed to the development of the neoplasias in both cases; long-term sun exposure may also have contributed to the development of the squamous cell carcinoma. To our knowledge, these 2 cases represent the first reports of sex skin neoplasia in chimpanzees. PMID:27053571

  17. Oral focal epithelial hyperplasia.

    PubMed

    Bassioukas, K; Danielides, V; Georgiou, I; Photos, E; Zagorianakou, P; Skevas, A

    2000-01-01

    Focal epithelial hyperplasia (FEH) or Heck disease, is a rare viral infection of the oral mucosa caused by HPV 13 or HPV 32. In Caucasians there have been only a few cases reported. We present the first case in Greece in a young Caucasian girl in which HPV 13 was detected with PCR analysis. The patient was successfully treated with CO2 laser.

  18. Mechanisms of disease: epithelial-mesenchymal transition and back again: does cellular plasticity fuel neoplastic progression?

    SciTech Connect

    Bissell, Mina J; Turley, Eva A.; Veiseh, Mandana; Radisky, Derek C.; Bissell, Mina J.

    2008-02-13

    Epithelial-mesenchymal transition (EMT) is a conversion that facilitates organ morphogenesis and tissue remodeling in physiological processes such as embryonic development and wound healing. A similar phenotypic conversion is also detected in fibrotic diseases and neoplasia, which is associated with disease progression. EMT in cancer epithelial cells often seems to be an incomplete and bi-directional process. In this Review, we discuss the phenomenon of EMT as it pertains to tumor development, focusing on exceptions to the commonly held rule that EMT promotes invasion and metastasis. We also highlight the role of the RAS-controlled signaling mediators, ERK1, ERK2 and PI3-kinase, as microenvironmental responsive regulators of EMT.

  19. [Gastric epithelial polyps (part two)].

    PubMed

    Espejo Romero, Luis Hernán; Navarrete Siancas, Jesús

    2004-01-01

    The following is a statistical report regarding gastric polyps: Frequency determined through endoscopic examinations was 3.6%. The terms hyperplastic polyps and adenomas were used for the classification of epithelial polyps, considering the suprafoveal hyperplasias within the hyperplastic polyps, provided they were elevated lesions. Out of 2,283 polyps, 1,959 were hyperplastic (86%) and 324 were adenomas (14%). When analyzing 780 polyps, 86 (11%) were found to have the Nakamura III category. With regard to topography, in an examination of 2253 polyps, hyperplastic polyps were located as follows: 325 (17%) in the antrum, 1402 (73%) in the body and 202 (10%) in the fundus. Adenomas had a different distribution: 212 (65%) in the antrum, 100 (31%) in the body and 12 (4%) in the fundus. Out of 371 hyperplastic polyps examined, 49% were pediculate and 51% were sessile; on the contrary, 86 % of adenomas were sessile. The average age was 66.2 years in adenoma carriers, 58.5 in those having hyperplastic polyps, and 57.4 for suprafoveal hyperplasias. In 287 adenomas, 94.1% of carriers were over 40 years old. Out of 92 adenomas examined, 21.7% evidenced adenoma metaplasia and 72.8% evidenced metaplasia in adjacent areas. Only 5.5% had no metaplasia. In 105 hyperplastic polyps studied, intestinal metaplasia was found: 16.7% in the polyp and 60% in adjacent areas. No metaplasia was found in the remaining 23.3%. Average size of the adenomas was 14 mm and of hyperplastic polyps, 11 mm. A total of 195 adenomas were smaller than 10 mm. The percentage of malignization in 288 adenomas examined was closely related to their size: 214 (66%) smaller than 20 mm, had a malignization percentage of 7%; 74 (34%) larger than 20 mm, had 51% malignization, and 86.2% malignization was found in adenomas of over 40 mm. Global malignization percentage of adenomas was 18%. However, when adenomas with high grade dysplasia in the 4.1 category of the Viena classification (non-invasive high grade

  20. Description of a new monoclonal antibody, FC-2.15, reactive with human breast cancer and other human neoplasias.

    PubMed

    Mordoh, J; Leis, S; Bravo, A I; Podhajcer, O L; Ballare, C; Capurro, M; Kairiyama, C; Bover, L

    1994-01-01

    FC-2.15 is an IgM monoclonal antibody (MAb) obtained by immunizing Balb/c mice with tumor epithelial cells from a human undifferentiated primary breast carcinoma. FC-2.15 reacts with 93.9% (31/33) of human breast primary tumors, independently of their histology and hormone receptor content. Moreover, FC-2.15 reacts with 79.6 +/- 13.8% (mean +/- SD) of total breast malignant tumor cells and with 88.7 +/- 9.9% of proliferating tumor cells. It recognizes other neoplasia such as colon cancer, squamous carcinoma and melanoma. Among the normal tissues examined, strong cross-reactivity was found with kidney proximal convolute tubules, bone marrow myeloid progeny, peripheral granulocytes and large bowel epithelium. Through Western blots, FC-2.15 recognizes three major bands of Mr 160 kDa, 130 kDa and 115 kDa in membrane extracts of MCF-7 cells grown in nude mice and of human breast carcinoma and three major bands of 250 kDa, 185 kDa and 105 kDa in membrane extracts of peripheral granulocytes. This MAb mediates complement- cytotoxicity against malignant cells, reducing the clonogenic capacity of breast primary tumor cells and MCF-7 cells to 35.6 +/- 41.2% and 11.7 +/- 4.8% of control values respectively, whereas that of normal bone marrow cells is not affected (104.7 +/- 17.4%).

  1. A Phase II Randomized Trial of Lycopene-Rich Tomato Extract Among Men with High-Grade Prostatic Intraepithelial Neoplasia.

    PubMed

    Gann, Peter H; Deaton, Ryan J; Rueter, Erika Enk; van Breemen, Richard B; Nonn, Larisa; Macias, Virgilia; Han, Misop; Ananthanarayanan, Viju

    2015-01-01

    A diverse body of evidence suggests that lycopene might inhibit prostate cancer development. We conducted a 6-mo repeat biopsy randomized trial among men with high-grade prostatic intraepithelial neoplasia (HGPIN). Here we report results for serum lycopene, prostate specific antigen (PSA) and insulin-like growth factor (IGF) proteins, histopathological review, and tissue markers for proliferation [minichromosome maintenance protein 2 (MCM-2)] and cell cycle inhibition (p27). Participants consumed placebo or tomato extract capsules containing 30 mg/day lycopene. Pre- and posttreatment biopsies were immunostained and digitally scored. Serum lycopene was determined by LC-MS-MS. In secondary analyses, pathologists blindly reviewed each biopsy to score histological features. Fifty-eight men completed the trial. Serum lycopene increased 0.55 μmol/L with treatment and declined 0.29 μmol/L with placebo. We observed no meaningful differences in PSA, IGF-1, or IGF binding protein 3 concentrations between groups, nor any differences in expression of MCM-2 or p27 in epithelial nuclei. Prevalences of cancer, HGPIN, atrophy, or inflammation posttreatment were similar; however, more extensive atrophy and less extensive HGPIN was more common in the lycopene group. Despite large differences in serum lycopene following intervention, no treatment effects were apparent on either the serum or benign tissue endpoints. Larger studies are warranted to determine whether changes observed in extent of HGPIN and focal atrophy can be replicated. PMID:26422197

  2. Constitutive activation of epithelial TLR4 augments inflammatory responses to mucosal injury and drives colitis-associated tumorigenesis

    PubMed Central

    Fukata, Masayuki; Shang, Limin; Santaolalla, Rebeca; Sotolongo, John; Pastorini, Cristhine; España, Cecilia; Ungaro, Ryan; Harpaz, Noam; Cooper, Harry S.; Elson, Greg; Kosco-Vilbois, Marie; Zaias, Julia; Perez, Maria T.; Mayer, Lloyd; Vamadevan, Arunan S.; Lira, Sergio A.; Abreu, Maria T.

    2010-01-01

    Chronic intestinal inflammation culminates in cancer and a link to TLR4 has been suggested by our observation that TLR4 deficiency prevents colitis-associated neoplasia. In the current study, we address the effect of the aberrant activation of epithelial TLR4 on induction of colitis and colitis-associated tumor development. We take a translational approach to address the consequences of increased TLR signaling in the intestinal mucosa. Mice transgenic for a constitutively-active TLR4 under the intestine-specific villin promoter (villin-TLR4 mice) were treated with DSS for acute colitis and azoxymethane-dextran sulfate sodium. TLR4 expression was analyzed by immunohistochemistry in colonic tissue from patients with ulcerative colitis and ulcerative colitis associated cancer. The effect of an antagonist TLR4 Ab was tested in prevention of colitis-associated neoplasia in the AOM-DSS model. Villin-TLR4 mice were highly susceptible to both acute colitis and colitis-associated neoplasia. Villin-TLR4 mice had increased epithelial expression of COX-2 and mucosal PGE2 production at baseline. Increased severity of colitis in villin-TLR4 mice was characterized by enhanced expression of inflammatory mediators and increased neutrophilic infiltration. In human UC samples, TLR4 expression was upregulated in almost all CAC and progressively increases with grade of dysplasia. As a proof of principle, a TLR4/MD-2 antagonist antibody inhibited colitis-associated neoplasia in the mouse model. Our results show that regulation of TLR's can affect the outcome of both acute colitis and its consequences—cancer. Targeting TLR4 and other TLR's may ultimately play a role in prevention or treatment of colitis-associated cancer. PMID:21674704

  3. The Spatial Predilection for Early Esophageal Squamous Cell Neoplasia

    PubMed Central

    Wang, Wen-Lun; Chang, I.-Wei; Chen, Chien-Chuan; Chang, Chi-Yang; Lin, Jaw-Town; Mo, Lein-Ray; Wang, Hsiu-Po; Lee, Ching-Tai

    2016-01-01

    Abstract Early esophageal squamous cell neoplasias (ESCNs) are easily missed with conventional white-light endoscopy. This study aimed to assess whether early ESCNs have a spatial predilection and the patterns of recurrence after endoscopic treatment. We analyzed the circumferential and longitudinal location of early ESCNs, as well as their correlations with exposure to carcinogens in a cohort of 162 subjects with 248 early ESCNs; 219 of which were identified by screening and 29 by surveillance endoscopy. The circumferential location was identified using a clock-face orientation, and the longitudinal location was identified according to the distance from the incisor. The most common circumferential and longitudinal distributions of the early ESCNs were found in the 6 to 9 o’clock quadrant (38.5%) and at 26 to 30 cm from the incisor (41.3%), respectively. A total of 163 lesions (75%) were located in the lower hemisphere arc, and 149 (68.4%) were located at 26 to 35 cm from the incisor. One hundred eleven (51%) early ESCNs were centered within the “hot zone” (i.e., lower hemisphere arc of the esophagus at 26 to 35 cm from the incisor), which comprised 20% of the esophageal area. Exposure to alcohol, betel nut, or cigarette was risk factors for the development of early ESCNs in the lower hemisphere. After complete endoscopic treatment, the mean annual incidence of metachronous tumors was 10%. In addition, 43% of the metachronous recurrent neoplasias developed within the “hot zone.” Cox regression analysis revealed that the index tumor within the hot zone (hazard ratio [HR]: 3.19; 95% confidence interval [CI]: 1.17–8.68; P = 0.02) and the presence of numerous Lugol-voiding lesions in the esophageal background mucosa were independent predictors for metachronous recurrence (HR: 4.61; 95% CI: 1.36–15.56; P = 0.01). We identified a hot zone that may be used to enhance the detection of early ESCNs during endoscopic screening and surveillance

  4. Sinonasal Neoplasia – Clinicopathological Profile And Importance of Computed Tomography

    PubMed Central

    Sarawagi, Radha; Raghuwanshi, Sameer; Yadav, Pankaj Kumar

    2015-01-01

    Background Nasal cavity and Paranasal sinus malignancies are very rare, in which maxillary sinus is the commonest, followed by ethmoid, frontal and sphenoid sinus. Computed Tomography (CT) & Magnetic Resonance Imaging (MRI) play a key role in diagnosis, staging and management of paranasal sinuses and nasal pathologies. Multiplanar imaging in CT helps better imaging of critical anatomical areas. Aim of our study was to study the incidence, clinical features, CT features and its importance in the management of sinonasal neoplasms. Materials and Methods This prospective study was carried out in a tertiary care hospital of MP, India. Consecutive 40 histologically proven cases of sinonasal neoplasia who visited the Department of Otorhinolaryngology and Radiotherapy are included in our study. Demography and clinical features were recorded. Cases of nasal and paranasal sinus masses diagnosed on CT attending ENT and Radiotherapy OPD or admitted in the Radiotherapy ward forms the material of this study. This included patients of both sexes and all ages. Histopathological examination was asked to confirm the diagnosis made on CT. Results There were total 40 cases of sinonasal neoplasia among which 24 were benign. Almost all the benign cases were seen in the age group <40 y with mean age of 20 y and most of the malignant cases were seen in the age group above 40 y with mean age of 55 y. In our study we found male preponderance with male female ratio of 4:1 in both benign and malignant conditions. The commonest presenting symptoms of the patients with sinonasal masses in our study was nasal obstruction (75%) and nasal discharge (67.5%) followed by nasal mass (65%), epistaxis (62.5%) and headache (60%). Angiofibroma and papilloma were the commonest benign lesions. Commonest malignant lesion was squamous cell carcinoma. Of the malignant Sinonasal tumours studied in our series, maxillary sinus was involved in 13, ethmoid sinuses and nasal cavity in 10 cases each, and frontal

  5. Angiomyolipoma With Epithelial Cysts.

    PubMed

    LeRoy, Michael A; Rao, Priya

    2016-06-01

    Angiomyolipoma with epithelial cysts is a rare mesenchymal tumor of the kidney that enters in the differential diagnosis of adult cystic renal neoplasms. These tumors demonstrate a slight female predominance and can present either incidentally or with symptoms, commonly flank pain and hematuria. Unlike conventional angiomyolipoma, this variant is characterized grossly by both solid and cystic areas, and histologically by the presence of single or multiple cysts lined by epithelial cells, a subepithelial "cambium-like" layer of small stromal cells with a prominent capillary vasculature, and a thick exterior wall composed of poorly formed fascicles of smooth muscle and thick-walled dysplastic blood vessels. Tumors show a distinct immunohistochemical profile and are often reactive for melanocytic markers (HMB-45 and Melan-A), as well as estrogen receptor and progesterone receptor. These tumors have an indolent clinical course, with no reports of progression or metastasis in reported cases thus far.

  6. Oral focal epithelial hyperplasia.

    PubMed

    López-Jornet, Pía; Camacho-Alonso, Fabio; Berdugo, Lucero

    2010-01-01

    Focal epithelial hyperplasia (FEH) is a benign, asymptomatic disease. It appears as papules, principally on the lower lip, although it can also be found on the retro-commissural mucosa and tongue and, less frequently, on the upper lip, gingiva and palate. FEH is caused by human papillomavirus subtype 13 or 32. The condition occurs in many populations and ethnic groups. We present the clinical case of a 31-year-old male with lesions that clinically and histologically corresponded to FEH.

  7. Feature-based analysis of mouse prostatic intraepithelial neoplasia in histological tissue sections.

    PubMed

    Ruusuvuori, Pekka; Valkonen, Mira; Nykter, Matti; Visakorpi, Tapio; Latonen, Leena

    2016-01-01

    This paper describes work presented at the Nordic Symposium on Digital Pathology 2015, in Linköping, Sweden. Prostatic intraepithelial neoplasia (PIN) represents premalignant tissue involving epithelial growth confined in the lumen of prostatic acini. In the attempts to understand oncogenesis in the human prostate, early neoplastic changes can be modeled in the mouse with genetic manipulation of certain tumor suppressor genes or oncogenes. As with many early pathological changes, the PIN lesions in the mouse prostate are macroscopically small, but microscopically spanning areas often larger than single high magnification focus fields in microscopy. This poses a challenge to utilize full potential of the data acquired in histological specimens. We use whole prostates fixed in molecular fixative PAXgene™, embedded in paraffin, sectioned through and stained with H&E. To visualize and analyze the microscopic information spanning whole mouse PIN (mPIN) lesions, we utilize automated whole slide scanning and stacked sections through the tissue. The region of interests is masked, and the masked areas are processed using a cascade of automated image analysis steps. The images are normalized in color space, after which exclusion of secretion areas and feature extraction is performed. Machine learning is utilized to build a model of early PIN lesions for determining the probability for histological changes based on the calculated features. We performed a feature-based analysis to mPIN lesions. First, a quantitative representation of over 100 features was built, including several features representing pathological changes in PIN, especially describing the spatial growth pattern of lesions in the prostate tissue. Furthermore, we built a classification model, which is able to align PIN lesions corresponding to grading by visual inspection to more advanced and mild lesions. The classifier allowed both determining the probability of early histological changes for uncategorized

  8. Helicobacter pylori and colorectal neoplasia: Is there a causal link?

    PubMed Central

    Papastergiou, Vasilios; Karatapanis, Stylianos; Georgopoulos, Sotirios D

    2016-01-01

    Ever since Helicobacter pylori (H. pylori) was recognized as an infectious cause of gastric cancer, there has been increasing interest in examining its potential role in colorectal carcinogenesis. Data from case-control and cross-sectional studies, mostly relying on hospital-based samples, and several meta-analyses have shown a positive statistical relationship between H. pylori infection and colorectal neoplasia. However, the possibility exists that the results have been influenced by bias, including the improper selection of patients and disparities with respect to potential confounders. While the evidence falls short of a definitive causal link, it appears that infection with H. pylori/H. pylori-related gastritis is associated with an increased, although modest, risk of colorectal adenoma and cancer. The pathogenic mechanisms responsible for this association remain uncertain. H. pylori has been detected in colorectal malignant tissues; however, the possibility that H. pylori is a direct activator of colonic carcinogenesis remains purely hypothetical. On the other hand, experimental data have indicated a series of potential oncogenic interactions between these bacteria and colorectal mucosa, including induction and perpetuation of inflammatory responses, alteration of gut microflora and release of toxins and/or hormonal mediators, such as gastrin, which may contribute to tumor formation. PMID:26811614

  9. Thyroid neoplasia in Marshall Islanders exposed to nuclear fallout

    SciTech Connect

    Hamilton, T.E.; van Belle, G.; LoGerfo, J.P.

    1987-08-07

    We studied the risk of thyroid neoplasia in Marshall Islanders exposed to radioiodines in nuclear fallout from the 1954 BRAVO thermonuclear test. We screened 7266 Marshall Islanders for thyroid nodules; the islanders were from 14 atolls, including several southern atolls, which were the source of the best available unexposed comparison group. Using a retrospective cohort design, we determined the prevalence of thyroid nodularity in a subgroup of 2273 persons who were alive in 1954 and who therefore were potentially exposed to fallout from the BRAVO test. For those 12 atolls previously thought to be unexposed to fallout, the prevalence of thyroid nodules ranged from 0.9% to 10.6%. Using the distance of each atoll from the test site as a proxy for the radiation dose to the thyroid gland, a weighted linear regression showed an inverse linear relationship between distance and the age-adjusted prevalence of thyroid nodules. Distance was the strongest single predictor in logistic regression analysis. A new absolute risk estimate was calculated to be 1100 excess cases/Gy/y/1 X 10(6) persons (11.0 excess cases/rad/y/1 million persons), 33% higher than previous estimates. We conclude that an excess of thyroid nodules was not limited only to the two northern atolls but extended throughout the northern atolls; this suggests a linear dose-response relationship.

  10. In vivo detection of cervical intraepithelial neoplasia by multimodal colposcopy

    NASA Astrophysics Data System (ADS)

    Ren, Wenqi; Qu, Yingjie; Pei, Jiaojiao; Xiao, Linlin; Zhang, Shiwu; Chang, Shufang; Smith, Zachary J.; Xu, Ronald X.

    2016-03-01

    Cervical cancer is the leading cause of cancer death for women in developing countries. Colposcopy plays an important role in early screening and detection of cervical intraepithelial neoplasia (CIN). In this paper, we developed a multimodal colposcopy system that combines multispectral reflectance, autofluorescence, and RGB imaging for in vivo detection of CIN, which is capable of dynamically recording multimodal data of the same region of interest (ROI). We studied the optical properties of cervical tissue to determine multi-wavelengths for different imaging modalities. Advanced algorithms based on the second derivative spectrum and the fluorescence intensity were developed to differentiate cervical tissue into two categories: squamous normal (SN) and high grade (HG) dysplasia. In the results, the kinetics of cervical reflectance and autofluorescence characteristics pre and post acetic acid application were observed and analyzed, and the image segmentation revealed good consistency with the gold standard of histopathology. Our pilot study demonstrated the clinical potential of this multimodal colposcopic system for in vivo detection of cervical cancer.

  11. Xiphophorus interspecies hybrids as genetic models of induced neoplasia.

    PubMed

    Walter, R B; Kazianis, S

    2001-01-01

    Fishes of the genus Xiphophorus (platyfishes and swordtails) are small, internally fertilizing, livebearing, and derived from freshwater habitats in Mexico, Guatemala, Belize, and Honduras. Scientists have used these fishes in cancer research studies for more than 70 yr. The genus is presently composed of 22 species that are quite divergent in their external morphology. Most cancer studies using Xiphophorus use hybrids, which can be easily produced by artificial insemination. Phenotypic traits, such as macromelanophore pigment patterns, are often drastically altered as a result of lack of gene regulation within hybrid fishes. These fish can develop large exophytic melanomas as a result of upregulated expression of these pigment patterns. Because backcross hybrid fish are susceptible to the development of melanoma and other neoplasms, they can be subjected to potentially deleterious chemical and physical agents. It is thus possible to use gene mapping and cloning methodologies to identify and characterize oncogenes and tumor suppressors implicated in spontaneous or induced neoplasia. This article reviews the history of cancer research using Xiphophorus and recent developments regarding DNA repair capabilities, mapping, and cloning of candidate genes involved in neoplastic phenotypes. The particular genetic complexity of melanoma in these fishes is analyzed and reviewed. PMID:11581522

  12. Laboratory management of cervical intraepithelial neoplasia: proposing a new paradigm.

    PubMed

    Herfs, Michael; Crum, Christopher P

    2013-03-01

    Since the discovery of human papillomavirus (HPV) type 16 in early 80s, the link between HPV and cervical cancer has been established with certainty, a function of the discovery and cloning of a range of HPV types associated with both cancer precursors (cervical intraepithelial neoplasia or CIN) and carcinomas and extensive epidemiologic, clinical, pathologic, and experimental data. These accumulated results have culminated in new paradigms of cancer prevention through screening and triage. Despite this, the management of women with CIN is still suboptimal and the overtreatment of these conditions still occurs, largely due to the lack of clarity regarding which precancerous lesions are most likely to progress in grade. Recently, a discrete population of cuboidal cells was discovered at the cervical squamocolumnar junction, the anatomic site where the large majority of HPV-related (pre)neoplastic lesions develop. These cells seem to be embryonic in nature and participate both in benign metaplasias and the initial phase of precancer development. This review summarizes the historical evolution of precursor management, assesses the potential role of this and other discoveries in segregating lower from higher-risk precursors, and examines their potential impact on the management of women with real or potential cervical cancer precursors.

  13. Committee Opinion No. 675 Summary: Management of Vulvar Intraepithelial Neoplasia.

    PubMed

    2016-10-01

    Vulvar intraepithelial neoplasia (VIN) is an increasingly common problem, particularly among women in their 40s. Although spontaneous regression has been reported, VIN should be considered a premalignant condition. Immunization with the quadrivalent or 9-valent human papillomavirus vaccine, which is effective against human papillomavirus genotypes 6, 11, 16, and 18, and 6, 11, 16, 18, 31, 33, 45, 52, and 58, respectively, has been shown to decrease the risk of vulvar high-grade squamous intraepithelial lesion (HSIL) (VIN usual type) and should be recommended for girls aged 11-12 years with catch-up through age 26 years if not vaccinated in the target age. There are no screening strategies for the prevention of vulvar cancer through early detection of vulvar HSIL (VIN usual type). Detection is limited to visual assessment with confirmation by histopathology when needed. Treatment is recommended for all women with vulvar HSIL (VIN usual type). Because of the potential for occult invasion, wide local excision should be performed if cancer is suspected, even if biopsies show vulvar HSIL. When occult invasion is not a concern, vulvar HSIL (VIN usual type) can be treated with excision, laser ablation, or topical imiquimod (off-label use). Given the relatively slow rate of progression, women with a complete response to therapy and no new lesions at follow-up visits scheduled 6 months and 12 months after initial treatment should be monitored by visual inspection of the vulva annually thereafter. PMID:27661648

  14. Committee Opinion No.675: Management of Vulvar Intraepithelial Neoplasia.

    PubMed

    2016-10-01

    Vulvar intraepithelial neoplasia (VIN) is an increasingly common problem, particularly among women in their 40s. Although spontaneous regression has been reported, VIN should be considered a premalignant condition. Immunization with the quadrivalent or 9-valent human papillomavirus vaccine, which is effective against human papillomavirus genotypes 6, 11, 16, and 18, and 6, 11, 16, 18, 31, 33, 45, 52, and 58, respectively, has been shown to decrease the risk of vulvar high-grade squamous intraepithelial lesion (HSIL) (VIN usual type) and should be recommended for girls aged 11-12 years with catch-up through age 26 years if not vaccinated in the target age. There are no screening strategies for the prevention of vulvar cancer through early detection of vulvar HSIL (VIN usual type). Detection is limited to visual assessment with confirmation by histopathology when needed. Treatment is recommended for all women with vulvar HSIL (VIN usual type). Because of the potential for occult invasion, wide local excision should be performed if cancer is suspected, even if biopsies show vulvar HSIL. When occult invasion is not a concern, vulvar HSIL (VIN usual type) can be treated with excision, laser ablation, or topical imiquimod (off-label use). Given the relatively slow rate of progression, women with a complete response to therapy and no new lesions at follow-up visits scheduled 6 months and 12 months after initial treatment should be monitored by visual inspection of the vulva annually thereafter. PMID:27661656

  15. Cervical Intraepithelial Neoplasia Is Associated With Genital Tract Mucosal Inflammation

    PubMed Central

    Mhatre, Mohak; McAndrew, Thomas; Carpenter, Colleen; Burk, Robert D.; Einstein, Mark H.; Herold, Betsy C.

    2013-01-01

    Background Clinical studies demonstrate increased prevalence of human papillomavirus (HPV)-associated disease in HIV-infected individuals and an increased risk of HIV acquisition in HPV-infected individuals. The mechanisms underlying this synergy are not defined. We hypothesize that women with cervical intraepithelial neoplasia (CIN) will exhibit changes in soluble mucosal immunity that may promote HPV persistence and facilitate HIV infection. Methods The concentrations of immune mediators and endogenous anti-Escherichia coli activity in genital tract secretions collected by cervicovaginal lavage were compared in HIV-negative women with high-risk HPV-positive (HRHPV+) CIN-3 (n = 37), HRHPV+ CIN-1 (n = 12), or PAP-negative control subjects (n = 57). Results Compared with control subjects, women with CIN-3 or CIN-1 displayed significantly higher levels of proinflammatory cytokines including interleukin (IL)-1α, IL-1β, and IL-8 (P < 0.002) and significantly lower levels of anti-inflammatory mediators and antimicrobial peptides, including IL-1 receptor antagonist, secretory leukocyte protease inhibitor (P < 0.01), and human β defensins 2 and 3 (P < 0.02). There was no significant difference in endogenous anti-E. coli activity after controlling for age and sample storage time. Conclusion HRHPV+ CIN is characterized by changes in soluble mucosal immunity that could contribute to HPV persistence. The observed mucosal inflammation suggests a mechanism that may also contribute to the epidemiologic link between persistent HPV and HIV. PMID:22801340

  16. Brain metastases from gestational trophoblastic neoplasia: review of pertinent literature.

    PubMed

    Piura, E; Piura, B

    2014-01-01

    Brain metastasis from gestational trophoblastic neoplasia (GTN) is rare with about 222 cases documented in the literature and an incidence of about 11% in living GTN patients. Brain metastasis from GTN was part of a disseminated disease in 90% of patients, single metastases in the brain - 80% and located in the cerebrum - 90%. Brain metastasis was the only manifestation of metastatic GTN in 11.3% of patients, appeared synchronously with metastatic GTN in other sites of the body - 30.6% and was diagnosed from 0.3 to 60 months after diagnosis of metastatic GTN in other sites (most often in the lung) - 58.1%. Overall, 83.9% of patients with brain metastases from GTN had also lung metastases from GTN. Brain metastases from GTN showed a greater tendency to be hemorrhagic compared to brain metastases from other primaries. In patients with brain metastases from GTN, the best outcome was achieved with multimodal therapy including craniotomy, whole brain radiotherapy, and EP-EMA or EMA-CO chemotherapy. Nonetheless, brain metastasis from GTN is a grave disease with a median survival time from diagnosis of brain metastasis of about 12 months.

  17. Anal cancer and intraepithelial neoplasia screening: A review

    PubMed Central

    Leeds, Ira L; Fang, Sandy H

    2016-01-01

    This review focuses on the early diagnosis of anal cancer and its precursor lesions through routine screening. A number of risk-stratification strategies as well as screening techniques have been suggested, and currently little consensus exists among national societies. Much of the current clinical rationale for the prevention of anal cancer derives from the similar tumor biology of cervical cancer and the successful use of routine screening to identify cervical cancer and its precursors early in the disease process. It is thought that such a strategy of identifying early anal intraepithelial neoplasia will reduce the incidence of invasive anal cancer. The low prevalence of anal cancer in the general population prevents the use of routine screening. However, routine screening of selected populations has been shown to be a more promising strategy. Potential screening modalities include digital anorectal exam, anal Papanicolaou testing, human papilloma virus co-testing, and high-resolution anoscopy. Additional research associating high-grade dysplasia treatment with anal cancer prevention as well as direct comparisons of screening regimens is necessary to develop further anal cancer screening recommendations. PMID:26843912

  18. Thyroid neoplasia in Marshall Islanders exposed to nuclear fallout.

    PubMed

    Hamilton, T E; van Belle, G; LoGerfo, J P

    1987-08-01

    We studied the risk of thyroid neoplasia in Marshall Islanders exposed to radioiodines in nuclear fallout from the 1954 BRAVO thermonuclear test. We screened 7266 Marshall Islanders for thyroid nodules; the islanders were from 14 atolls, including several southern atolls, which were the source of the best available unexposed comparison group. Using a retrospective cohort design, we determined the prevalence of thyroid nodularity in a subgroup of 2273 persons who were alive in 1954 and who therefore were potentially exposed to fallout from the BRAVO test. For those 12 atolls previously thought to be unexposed to fallout, the prevalence of thyroid nodules ranged from 0.9% to 10.6%. Using the distance of each atoll from the test site as a proxy for the radiation dose to the thyroid gland, a weighted linear regression showed an inverse linear relationship between distance and the age-adjusted prevalence of thyroid nodules. Distance was the strongest single predictor in logistic regression analysis. A new absolute risk estimate was calculated to be 1100 excess cases/Gy/y/1 X 10(6) persons (11.0 excess cases/rad/y/1 million persons), 33% higher than previous estimates. We conclude that an excess of thyroid nodules was not limited only to the two northern atolls but extended throughout the northern atolls; this suggests a linear dose-response relationship.

  19. A Possible New Multiple Endocrine Neoplasia Mutation in a Patient with a Prototypic Multiple Endocrine Neoplasia Presentation

    PubMed Central

    Buzzola, Rino; Kurukulasuriya, Lilamani Romayne; Touza, Mariana; Litofsky, Norman S.; Brietzke, Stephen; Sowers, James R.

    2016-01-01

    Background Multiple endocrine neoplasia (MEN) type 1 syndrome is an uncommon inherited disorder characterized by the occurrence of tumors involving two or more endocrine glands. These tumors include pheochromocytoma, adrenal cortical and neuroendocrine tumors including (bronchopulmonary, thymic, gastric), lipomas, angiofibromas, collagenomas, and meningiomas. MEN-4 is very rare and has been characterized by the occurrence of parathyroid and anterior pituitary tumors in association with tumors of the adrenals, kidneys, and reproductive organs. Summary We report the case of a 40-year-old male without significant family history of endocrine disease who was found to have primary hyperparathyroidism, a pituitary tumor causing acromegaly, thyroid cancer, renal cell carcinoma, and pancreatic cysts. We posit that this represents a new version of MEN-4. While renal tumors (angiomyolipoma) have been reported as part of the MEN-4 phenotype, to our knowledge, this is the first case reported of the association of MEN-1 and/or MEN-4 phenotype with this unique constellation of tumors, including renal cell carcinoma. Interestingly, this patient tested negative (DNA sequencing/deletion) for MEN-1 (menin), MEN-4 (CDKN1B) and VHL genes. Key Message Thus, while this case has clinical characteristics consistent with either MEN-1 or MEN-4, it may represent a unique genetic variant. PMID:26989398

  20. Epithelial Cell Responses to Infection with Human Papillomavirus

    PubMed Central

    2012-01-01

    Summary: Human papillomavirus (HPV) infection of the genital tract is common in young sexually active individuals, the majority of whom clear the infection without overt clinical disease. Most of those who do develop benign lesions eventually mount an effective cell-mediated immune (CMI) response, and the lesions regress. Regression of anogenital warts is accompanied histologically by a CD4+ T cell-dominated Th1 response; animal models support this and provide evidence that the response is modulated by antigen-specific CD4+ T cell-dependent mechanisms. Failure to develop an effective CMI response to clear or control infection results in persistent infection and, in the case of the oncogenic HPVs, an increased probability of progression to high-grade intraepithelial neoplasia and invasive carcinoma. Effective evasion of innate immune recognition seems to be the hallmark of HPV infections. The viral infectious cycle is exclusively intraepithelial: there is no viremia and no virus-induced cytolysis or cell death, and viral replication and release are not associated with inflammation. HPV globally downregulates the innate immune signaling pathways in the infected keratinocyte. Proinflammatory cytokines, particularly the type I interferons, are not released, and the signals for Langerhans cell (LC) activation and migration, together with recruitment of stromal dendritic cells and macrophages, are either not present or inadequate. This immune ignorance results in chronic infections that persist over weeks and months. Progression to high-grade intraepithelial neoplasia with concomitant upregulation of the E6 and E7 oncoproteins is associated with further deregulation of immunologically relevant molecules, particularly chemotactic chemokines and their receptors, on keratinocytes and endothelial cells of the underlying microvasculature, limiting or preventing the ingress of cytotoxic effectors into the lesions. Recent evidence suggests that HPV infection of basal

  1. Differential Sensitivity of Mouse Epithelial Tissues to the Polyomavirus Middle T Oncogene

    PubMed Central

    Cecena, Grace; Wen, Fang; Cardiff, Robert D.; Oshima, Robert G.

    2006-01-01

    To determine how different epithelial cell types respond to the same oncogenic stimulation, we have used a modified human keratin 18 gene to conditionally express the polyomavirus middle T antigen (PyMT) oncogene in simple epithelial tissues of transgenic mice. Activation of PyMT expression by transgenic Cre recombinase in mammary epithelial cells resulted in carcinomas in all bitransgenic females. PyMT expression induced by K18-driven Cre in internal epithelial organs resulted in pancreatic acinar metaplasia and ductal dysplasia with remarkable desmoplastic stromal responses in all 25 bitransgenic mice. Hepatoma formation with altered lipid metabolism and gastric adenocarcinoma occurred in 96 and 54% of these mice, respectively. Elevated PyMT RNA expression also correlated with intraepithelial neoplasia in the prostate. Activated Erk2 was found in mammary tumors, pancreatic tissues, and affected livers. Hes1 RNA, a target of Notch signaling that has been implicated downstream of Ras pathway activation, was elevated in pancreatic and liver lesions. The variety of responses of different epithelia to PyMT demonstrates the importance of the differentiated state in interpreting oncogenic signals. PMID:16400032

  2. Aberrant epithelial GREM1 expression initiates colonic tumorigenesis from cells outside the stem cell niche.

    PubMed

    Davis, Hayley; Irshad, Shazia; Bansal, Mukesh; Rafferty, Hannah; Boitsova, Tatjana; Bardella, Chiara; Jaeger, Emma; Lewis, Annabelle; Freeman-Mills, Luke; Giner, Francesc C; Rodenas-Cuadrado, Pedro; Mallappa, Sreelakshmi; Clark, Susan; Thomas, Huw; Jeffery, Rosemary; Poulsom, Richard; Rodriguez-Justo, Manuel; Novelli, Marco; Chetty, Runjan; Silver, Andrew; Sansom, Owen J; Greten, Florian R; Wang, Lai Mun; East, James E; Tomlinson, Ian; Leedham, Simon J

    2015-01-01

    Hereditary mixed polyposis syndrome (HMPS) is characterized by the development of mixed-morphology colorectal tumors and is caused by a 40-kb genetic duplication that results in aberrant epithelial expression of the gene encoding mesenchymal bone morphogenetic protein antagonist, GREM1. Here we use HMPS tissue and a mouse model of the disease to show that epithelial GREM1 disrupts homeostatic intestinal morphogen gradients, altering cell fate that is normally determined by position along the vertical epithelial axis. This promotes the persistence and/or reacquisition of stem cell properties in Lgr5-negative progenitor cells that have exited the stem cell niche. These cells form ectopic crypts, proliferate, accumulate somatic mutations and can initiate intestinal neoplasia, indicating that the crypt base stem cell is not the sole cell of origin of colorectal cancer. Furthermore, we show that epithelial expression of GREM1 also occurs in traditional serrated adenomas, sporadic premalignant lesions with a hitherto unknown pathogenesis, and these lesions can be considered the sporadic equivalents of HMPS polyps.

  3. From hyperplasia to frank breast neoplasia. Carcinogenesis. Immunoprevention.

    PubMed

    Corocleanu, M

    1995-01-01

    There is strong evidence that in advanced cases of breast fibrocystic disease, the risk of cancer is elevated. Cyclic breast glandular hyperplasia is commonly associated with mastodynia and/or breast fibrocystic disease. The administration of progestins, antiestrogens and/or local progesteron, results in some cases in a desensibilisation, accompanied by loss in responsiveness to hormonal therapy. Out of 167 patients (pts) suffering from mastodynia and/or breast fibrocystic disease with positive delayed-type hypersensitivity (DTHS) reactions to a pharmaceutical Placenta Suspension (PS), when injected intradermally, in 87 pts. who failed to respond to hormonal therapy, a vaccine preparade from PS admixed with an adjuvant (BCG), was administrated in one intradermal injection (0.1). In all the pts. recruited into the study, a complete remission of the symptoms occurred and in the majority of cases lasted throughout the 12 month follow-up period. The essential factor of relative hyper-estrinism, initiates breast epithelial hyperplasia and also increases stromal ground substance, which has the propensity to fibrous reorganisation. A true or relative hypoxia results, as a consequence of connective tissue sclerosis and epithelial thickness, constituting a supplementary factor for further epithelial proliferation. The risk of gene faults is greater when hypoxia operates at cell viability level and for long enough duration. Within the frame of persistent multicellular proliferative potential, a basic shift in energy metabolism is accompanied by appearance of fetal isoenzymes and of membrane glycoproteins, that induces a host immunological reaction (emphasised by PS).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7556289

  4. [Focal epithelial hyperplasia].

    PubMed

    Delgado, Yolanda; Torrelo, Antonio; Colmenero, Isabel; Zambrano, Antonio

    2005-12-01

    Focal epithelial hyperplasia (FEH) is a benign proliferation of the oral mucosa with well defined clinical and histological characteristics. It has been associated with infection of the oral mucosa by types 13 and 32 of the human papillomavirus (HPV), and to a lesser extent, with other types. Its clinical course is variable, although it usually persists for months or years; cases with spontaneous resolution have been described, as have others with prolonged persistence. We present the case of an Ecuadorian boy whose visit was motivated by lesions in the oral mucosa consistent with a diagnosis of FEH, which were confirmed in the histological study, and in which HPV type 13 DNA was identified.

  5. [Focal epithelial hyperplasia].

    PubMed

    Carlino, P; Di Felice, R; Fiore-Donno, G; Samson, J

    1991-05-01

    Five cases of "focal epithelial hyperplasia" (FEH) of the oral mucosa observed in Switzerland are reported. The patients were of Turkish and North African extraction. The lesions of FEH were multiple, painless, located at various sites of the oral mucosa including the tongue in the form of either soft papules or hard nodules. Evidence of a human papilloma virus origin was ascertained. Among the 1067 cases reported in the literature and reviewed for this study, this condition has been described to occur among American Indians, Eskimos and North African, also in Israeli and European cases the disorder was often reported in individuals of Turkish or North African extraction.

  6. Embryological pigment epithelial dystrophies.

    PubMed

    François, J

    1976-01-01

    The embryological pigment epithelial dystrophies may be due, although rather rarely, to chemical factors, such as antibiotics and thalidomide, to ionizing radiation and to infectious factors, syphilis or viral infections, such as mumps, measles, varicella, or cytomegalovirus. The most frequent and the most typical dystrophy is, nevertheless, the rubella epitheliopathy with its widespread scattered black pigment deposits, found predominantly in the posterior pole, and its unaffected visual functions. The macular dystrophy associated with deaf-mutism is also often due to a maternal rubella infection.

  7. Differential effects of human papillomavirus type 6, 16, and 18 DNAs on immortalization and transformation of human cervical epithelial cells

    SciTech Connect

    Pecoraro, G.; Morgan, D.; Defendi, V. )

    1989-01-01

    The human papillomaviruses (HPVs) are associated with specific benign and malignant lesions of the skin and mucosal epithelia. Cloned viral DNAs from HPV types 6b, 16, and 18 associated with different pathological manifestations of genital neoplasia in vivo were introduced into primary human cervical epithelial cells by electroporation. Cells transfected with HPV16 or HPV18 DNA acquired indefinite lifespans, distinct morphological alterations, and anchorage-independent growth (HPV18), and contain integrated transcriptionally active viral genomes. HPV6b or plasmid electroporated cells senesced at low passage. The alterations in growth and differentiation of the cells appear to reflect the progressive oncogenic processes that result in cervical carcinoma in vivo.

  8. Oncogenic association of specific human papillomavirus types with cervical neoplasia.

    PubMed

    Lorincz, A T; Temple, G F; Kurman, R J; Jenson, A B; Lancaster, W D

    1987-10-01

    Molecular hybridization analysis of human papillomavirus (HPV) DNA from 190 cervical biopsy specimens from women in the United States, Brazil, and Peru revealed viral sequences in 2 (9%) of 23 biopsy specimens of normal mature squamous epithelium, 7 (44%) of 16 biopsy specimens of metaplastic squamous epithelia, 60 (77%) of 78 cervical intraepithelial neoplasia (CIN), 57 (89%) of 64 invasive squamous carcinomas, and 8 (89%) of 9 endocervical adenocarcinomas. HPV typing by DNA hybridization revealed HPV 6 and HPV 11 sequences in metaplastic squamous epithelia, CIN I, and CIN II, but not in CIN III lesions or invasive carcinomas. HPV 16 was detected in metaplastic epithelium and in nearly half of the invasive squamous carcinomas and adenocarcinomas. It was present in 31% of CIN lesions, increasing in frequency with the severity of CIN from 20% of CIN I to 50% of CIN III. HPV 16 showed a striking difference in geographic distribution, being detected in 36% of the carcinomas from the United States compared to 64% of the carcinomas from Brazil and Peru. HPV 18 was found in metaplastic epithelia and in 17% of carcinomas but in only 1% of CIN lesions. HPV 31 was not found in metaplastic epithelium but was present in 6% of carcinomas and in 18% of CIN lesions. In addition, a group of uncharacterized HPVs, not corresponding to any of the probes used, was found in 5% of normal and metaplastic epithelia and in 18% of CIN and 19% of invasive cancers. These results suggest that individual HPV types that infect the cervix have varying degrees of oncogenic association. HPV 6 and HPV 11 appear to have very little oncogenic association, HPV 31 has low oncogenic association, and HPV 16 and HPV 18 have high oncogenic association. PMID:2821311

  9. Current treatment options for management of anal intraepithelial neoplasia

    PubMed Central

    Weis, Stephen E

    2013-01-01

    Anal squamous cell cancer is an uncommon malignancy caused by infection with oncogenic strains of Human papilloma virus. Anal cancer is much more common in immunocompromised persons, including those infected with Human immunodeficiency virus. High-grade anal intraepithelial neoplasia (HGAIN), the precursor of anal cancer, is identified by clinicians providing care for patients with anorectal disease, and is increasingly being identified during screening of immunosuppressed patients for anal dysplasia. The traditional treatment for HGAIN has been excision of macroscopic disease with margins. This approach is effective for patients with small unifocal HGAIN lesions. Patients with extensive multifocal HGAIN frequently have recurrence of HGAIN after excision, and may have postoperative complications of anal stenosis or fecal incontinence. This led to the suggestion by some that treatment for HGAIN should be delayed until patients developed anal cancer. Alternative approaches in identification and treatment have been developed to treat patients with multifocal or extensive HGAIN lesions. High-resolution anoscopy combines magnification with anoscopy and is being used to identify HGAIN and determine treatment margins. HGAIN can then be ablated with a number of modalities, including infrared coagulation, CO2 laser, and electrocautery. These methods for HGAIN ablation can be performed with local anesthesia on outpatients and are relatively well tolerated. High-resolution anoscopy-directed HGAIN ablation is evolving into a standard approach for initial treatment and then subsequent monitoring of a disease which should be expected to be recurrent. Another treatment approach for HGAIN is topical treatment, principally with 5-fluorouracil or imiquimod. Topical therapies have the advantage of being nonsurgical and are well suited for treating widespread multifocal disease. Topical treatments have the disadvantage of requiring extended treatment courses and causing a symptomatic

  10. Association between folate status and cervical intraepithelial neoplasia

    PubMed Central

    Zhao, W; Hao, M; Wang, Y; Feng, N; Wang, Z; Wang, W; Wang, J; Ding, L

    2016-01-01

    Background/Objectives: To investigate the effect of folate status on cervical intraepithelial neoplasia (CIN) progression and its relationship with high-risk human papillomavirus (hrHPV). Subjects/Methods: We evaluated 20 000 sexually active women aged <65 years in Yangqu County by using a questionnaire; the subjects were also screened using the ThinPrep cytologic test (TCT). Patients with abnormal TCT results (other than glandular cell abnormalities) who were willing to provide informed consent were further diagnosed using colposcopy and histopathological examination. We investigated 247 cases of low-grade cervical squamous intraepithelial lesions (LSIL), 125 cases of high-grade cervical squamous intraepithelial lesions (HSIL) and 877 controls. A 24-item food frequency questionnaire was filled out by the investigator to estimate the consumption of dietary folate. Positivity for hrHPV from residual exfoliated cervical cells was tested; serum folate was also measured. Results: The hrHPV infection rate in HSIL patients (77.6%) was higher than that in LSIL (33.2%) and control (32.0%) patients. Dietary folate intakes in controls, LSIL and HSIL were 306.9±176.6, 321.8±168.0 and 314.7±193.8 μg/kcal, respectively. The levels of serum folate in controls, LSIL and HSIL were 18.2±7.9, 15.9±7.1 and 14.3±7.5 nmol/l, respectively. Increased CIN correlated with higher rates of hrHPV infection and lower levels of serum folate. Conclusions: Low levels of serum folate may increase the risk of CIN progression. Furthermore, potential synergy may exist between low serum folate levels and hrHPV infection to promote CIN development. PMID:27026426

  11. RAP1 GTPase Overexpression is Associated with Cervical Intraepithelial Neoplasia

    PubMed Central

    Pascoal-Xavier, Marcelo Antonio; Figueiredo, Anna Carolina Cançado; Gomes, Luciana Inácia; Peruhype-Magalhães, Vanessa; Calzavara-Silva, Carlos Eduardo; Costa, Marcelo Azevedo; Reis, Ilka Afonso; Bonjardim, Claudio Antônio; Kroon, Erna Geessien

    2015-01-01

    RAP1 (RAS proximate 1), a small GTP-binding protein of the RAS superfamily, is a putative oncogene that is highly expressed in several malignant cell lines and types of cancers, including some types of squamous cell carcinoma. However, the participation of RAP1 in cervical carcinogenesis is unknown. We conducted a cross-sectional study of paraffin-embedded cervical biopsies to determine the association of RAP1 with cervical intraepithelial neoplasia (CIN). Standard and quantitative immunohistochemistry assessment of RAP1 expression in fixed tissue was performed on 183 paraffin-embedded cervical biopsies that were classified as normal or non-dysplastic mucosa (NDM) (n = 33); CIN grade 1 (n = 84) and CIN grade 2/3 (n = 66). A gradual increase in RAP1 expression in NDM < CIN 1 < CIN 2/3 (p<0.001) specimens was observed and was in agreement with the histopathologic diagnosis. A progressive increase in the RAP1 expression levels increased the risk of CIN 1 [odds ratio (OR) = 3.50; 95% confidence interval (CI) 1.30-10.64] 3.5 fold and the risk of CIN 2/3 (OR = 19.86, 95% CI 6.40-70.79) nearly 20 fold when compared to NDM. In addition, stereotype ordinal regression analysis showed that this progressive increase in RAP1 expression more strongly impacted CIN 2/3 than CIN 1. Our findings suggest that RAP1 may be a useful biomarker for the diagnosis of CIN. PMID:25856570

  12. High Resolution Microendoscopy for Quantitative Diagnosis of Esophageal Neoplasia

    NASA Astrophysics Data System (ADS)

    Shin, Dongsuk

    Esophageal cancer is the eighth most common cancer in the world. Cancers of the esophagus account for 3.8% of all cases of cancers, with approximately 482,300 new cases reported in 2008 worldwide. In the United States alone, it is estimated that approximately 18,000 new cases will be diagnosed in 2013, and 15,210 deaths are expected. Despite advances in surgery and chemoradiation therapy, these advances have not led to a significant increase in survival rates, primarily because diagnosis often at an advanced and incurable stage when treatment is more difficult and less successful. Accurate, objective methods for early detection of esophageal neoplasia are needed. Here, quantitative classification algorithms for high resolution miscroendoscopic images were developed to distinguish between esophageal neoplastic and non-neoplastic tissue. A clinical study in 177 patients with esophageal squamous cell carcinoma (ESCC) was performed to evaluate the diagnostic performance of the classification algorithm in collaboration with the Mount Sinai Medical Center in the United States, the First Hospital of Jilin University in China, and the Cancer Institute and Hospital, the Chinese Academy of Medical Science in China. The study reported a sensitivity and specificity of 93% and 92%, respectively, in the training set, 87% and 97%, respectively, in the test set, and 84% and 95%, respectively, in an independent validation set. Another clinical study in 31 patients with Barrett's esophagus resulted in a sensitivity of 84% and a specificity of 85%. Finally, a compact, portable version of the high resolution microendoscopy (HRME) device using a consumer-grade camera was developed and a series of biomedical experimental studies were carried out to assess the capability of the device.

  13. Gigantism in sibling unrelated to multiple endocrine neoplasia: case report.

    PubMed

    Matsuno, A; Teramoto, A; Yamada, S; Kitanaka, S; Tanaka, T; Sanno, N; Osamura, R Y; Kirino, T

    1994-11-01

    The cases of gigantism sisters with somatotroph adenomas unrelated to multiple endocrine neoplasia (MEN) Type 1 are reported. The sisters grew rapidly since they were 5 or 6 years old and were diagnosed to have gigantism with pituitary adenoma by computed tomographic scan and magnetic resonance imaging. A serum endocrinological examination showed the elevated growth hormone values. After thyroxine-releasing hormone stimulation, growth hormone values exhibited a paradoxical rise. They were supposed to be unrelated to MEN Type 1, because analysis of the 11th chromosomes and the other endocrine functions were normal. They were operated on by the transphenoidal method. Immunohistochemical staining of both tumor specimens confirmed somatotroph adenomas. Pituitary adenoma associated with MEN Type 1 is a well-recognized entity. However, the sporadic occurrence of pituitary adenoma unrelated to MEN Type 1, especially in siblings, is extremely rare. Fifteen cases of pituitary adenomas in siblings were described in the literature. As for gigantism, only two brothers were reported. Our case of gigantism sisters is the second sporadic case. In our review of the isolated cases of pituitary adenoma in siblings described in the literature, 12 (70%) of 17 cases including ours are acromegaly or gigantism. This incidence is much higher than that of MEN Type 1 patients with pituitary adenomas. The cause of the familial occurrence of pituitary adenomas is still unclear, although autosomal recessive inheritance has been suggested. It has been stated that point mutations in codon 201 or 227 of the Gs alpha gene located in chromosome 20 were found in about 35 to 40% of somatotroph adenomas.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7838348

  14. Cushing’s Syndrome in Multiple Endocrine Neoplasia Type 1

    PubMed Central

    Simonds, William F.; Varghese, Sarah; Marx, Stephen J.; Nieman, Lynnette K.

    2011-01-01

    Summary Objective In patients with multiple endocrine neoplasia type 1 (MEN1), Cushing’s syndrome (CS) from endogenous hypercortisolism can result from pituitary, adrenal, or other endocrine tumors. The purpose of this study was to characterize the range of presentations of CS in a large series of MEN1 patients. Design Retrospective review of NIH Clinical Center inpatient records over an approximately 40 year period. Patients 19 patients (8 males, 11 females) with CS and MEN1. Measurements Biochemical, imaging, surgical, and pathological findings. Results An etiology was determined for 14 of the 19 patients with CS and MEN1: 11 (79%) had Cushing’s disease (CD) and three (21%) had ACTH-independent CS due to adrenal tumors, frequencies indistinguishable from sporadic CS. Three of 11 MEN1 patients with CD (27%) had additional non-ACTH secreting pituitary microadenomas identified at surgery, an incidence 10-fold higher than in sporadic CD. Ninety-one percent of MEN1 patients with CD were cured after surgery. Two of three MEN1 patients with ACTH-independent CS (67%) had adrenocortical carcinoma. One patient with adrenal cancer and another with adrenal adenoma were cured by unilateral adrenalectomy. No case of ectopic ACTH secretion was identified in our patient cohort. The etiology of CS could not be defined in five patients; in three of these, hypercortisolism appeared to resolve spontaneously. Conclusions The tumor multiplicity of MEN1 can be reflected in the anterior pituitary, MEN1-associated ACTH-independent CS may be associated with aggressive adrenocortical disease, and an etiology for CS in MEN1 may be elusive in a substantial minority of patients. PMID:21916912

  15. Gigantism in sibling unrelated to multiple endocrine neoplasia: case report.

    PubMed

    Matsuno, A; Teramoto, A; Yamada, S; Kitanaka, S; Tanaka, T; Sanno, N; Osamura, R Y; Kirino, T

    1994-11-01

    The cases of gigantism sisters with somatotroph adenomas unrelated to multiple endocrine neoplasia (MEN) Type 1 are reported. The sisters grew rapidly since they were 5 or 6 years old and were diagnosed to have gigantism with pituitary adenoma by computed tomographic scan and magnetic resonance imaging. A serum endocrinological examination showed the elevated growth hormone values. After thyroxine-releasing hormone stimulation, growth hormone values exhibited a paradoxical rise. They were supposed to be unrelated to MEN Type 1, because analysis of the 11th chromosomes and the other endocrine functions were normal. They were operated on by the transphenoidal method. Immunohistochemical staining of both tumor specimens confirmed somatotroph adenomas. Pituitary adenoma associated with MEN Type 1 is a well-recognized entity. However, the sporadic occurrence of pituitary adenoma unrelated to MEN Type 1, especially in siblings, is extremely rare. Fifteen cases of pituitary adenomas in siblings were described in the literature. As for gigantism, only two brothers were reported. Our case of gigantism sisters is the second sporadic case. In our review of the isolated cases of pituitary adenoma in siblings described in the literature, 12 (70%) of 17 cases including ours are acromegaly or gigantism. This incidence is much higher than that of MEN Type 1 patients with pituitary adenomas. The cause of the familial occurrence of pituitary adenomas is still unclear, although autosomal recessive inheritance has been suggested. It has been stated that point mutations in codon 201 or 227 of the Gs alpha gene located in chromosome 20 were found in about 35 to 40% of somatotroph adenomas.(ABSTRACT TRUNCATED AT 250 WORDS)

  16. COMPUTED TOMOGRAPHIC FEATURES OF PHARYNGEAL NEOPLASIA IN 25 DOGS.

    PubMed

    Carozzi, Gregorio; Zotti, Alessandro; Alberti, Monica; Rossi, Federica

    2015-01-01

    Computed tomography (CT) is commonly used to investigate head tumors in dogs, however little information is available for lesions of the pharyngeal area. The purpose of this multicentric, retrospective, cross-sectional study was to describe the CT findings in a sample of dogs with pathologically confirmed pharyngeal neoplasia and determine whether any CT features allowed differentiation of tumor type. Location of lesions, size and shape, margins, relationship with surrounding structures and vessels, attenuation characteristics and enhancement pattern, regional lymph node changes, and presence of metastasis were recorded by three observers (1 DECVDI). The effect of final diagnosis on each CT feature was tested. A total of 25 dogs were included: 15 with carcinomas, five sarcomas, four melanomas, and one lymphoma. The oropharynx and laryngopharynx were more frequently involved. Among tumor groups, lesions were of similar size, irregularly shaped, had ill-defined margins, and had moderate-to-marked heterogeneous contrast enhancement. Lysis of hyoid bones was recorded in two carcinomas and infiltration of the lingual artery occurred in one case. Marked medial retropharyngeal lymphoadenomegaly was recorded in 11 of 14 carcinomas, in all sarcomas and in two of four melanomas. The single lymphoma case showed ill-defined thickening of the oropharyngeal and laryngeal wall with retropharyngeal and mandibular lymphadenomegaly. Lung metastases were found in two of five sarcomas and two of four melanomas. Findings from the current study did not support the hypothesis that CT features could be used to predict pharyngeal tumor type in dogs. However, CT was helpful for determining mass extension, lymph node involvement, and distant metastatic spread. PMID:26173553

  17. How big is this neoplasia? live colonoscopic size measurement using the Infocus-Breakpoint.

    PubMed

    Chadebecq, F; Tilmant, C; Bartoli, A

    2015-01-01

    Colonoscopy is the reference medical examination for early diagnosis and treatment of colonic diseases. This minimally invasive technique allows endoscopists to explore the colon cavity and remove neoplasias - abnormal growths of tissue - which may develop into malignant tumors. The size, shape and appearance of a neoplasia are essential cues for diagnostic. However, the size is difficult to estimate because the absolute scale of the observed tissue is not directly conveyed in the 2D colonoscopic images. An erroneous size estimate may lead to inappropriate treatment. There currently exist no solutions to reproducible neoplasia size measurement adapted to colonoscopy. We propose a colonoscopic size measurement system for neoplasias. By using a simple planar geometry, the key technical problem is reduced to resolving scale. Our core contribution is introducing the Infocus-Breakpoint (IB) that allows us to resolve scale from a regular colonoscopic video. We define the IB as the lower limit of the colonoscope's depth of field. The IB corresponds to a precise colonoscope to tissue distance, called the reference depth, which we calibrate preoperatively. We detect the IB intraoperatively thanks to two novel modules: deformable Blur-Estimating Tracking (BET) and Blur-Model Fitting (BMF). With our system, the endoscopist may interactively measure the length and area of a neoplasia in a 2D colonoscopic image directly. Our system needs no hardware modification to standard monocular colonoscopes, yet reaching a size measurement accuracy of the order of a millimeter, as shown on several phantom and patient datasets.

  18. Association of Intrauterine Device (IUD) and Cervical Neoplasia - A Study in a Poor Nigerian Population

    PubMed Central

    Chigbu, Chibuike Ogwuegbu; Ozumba, Benjamin Chukwuma; Oguanuo, Theophilus Chimezie; Ezeonu, Paul Olisaemeka

    2016-01-01

    Introduction Intrauterine Device (IUD) is a contraceptive method used by women of reproductive age group. However, there are conflicting reports on the association between IUD and cervical neoplasia. These controversies may further hamper the poor uptake of modern contraception in Nigeria. Aim This study was therefore aimed at evaluating the association between IUD and cervical neoplasia. Materials and Methods This was a case control study in which Pap smear results of 156 participants on IUD were compared with those of 156 non-users of modern contraception. The participants who were found to have abnormal cervical smear cytology results were further subjected to colposcopy. Biopsy specimens for histology were collected from the participants with obvious cervical lesions or those with suspicious lesions on colposcopy. The results were analysed with descriptive and inferential statistics at 95% level of confidence. Results Seven (4.5%) and 2(1.3%) of participants using IUD had Cervical Intraepithelial Neoplasia (CIN) 1 and CIN 2 respectively. Also, 5(3.2%) and 1(0.6%) of non-users of modern contraception had CIN 1 and CIN 2 respectively. The prevalence of cervical neoplasia among all the participants was 4.8%. Although, the proportion of women who had CIN was more among participants using IUD than non-users of modern contraception, the difference was not statistically significant. Conclusion There was no significant association between IUD and cervical neoplasia in this study. PMID:27504358

  19. Simple Epithelial Keratins.

    PubMed

    Strnad, Pavel; Guldiken, Nurdan; Helenius, Terhi O; Misiorek, Julia O; Nyström, Joel H; Lähdeniemi, Iris A K; Silvander, Jonas S G; Kuscuoglu, Deniz; Toivola, Diana M

    2016-01-01

    Simple epithelial keratins (SEKs) are the cytoplasmic intermediate filament proteins of single-layered and glandular epithelial cells as found in the liver, pancreas, intestine, and lung. SEKs have broad cytoprotective functions, which are facilitated by dynamic posttranslational modifications and interaction with associated proteins. SEK filaments are composed of obligate heteropolymers of type II (K7, K8) and type I (K18-K20, K23) keratins. The multifaceted roles of SEKs are increasingly appreciated due to findings obtained from transgenic mouse models and human studies that identified SEK variants in several digestive diseases. Reorganization of the SEK network into aggregates called Mallory-Denk bodies (MDBs) is characteristic for specific liver disorders such as alcoholic and nonalcoholic steatohepatitis. To spur further research on SEKs, we here review the methods and potential caveats of their isolation as well as possibilities to study them in cell culture. The existing transgenic SEK mouse models, their advantages and potential drawbacks are discussed. The tools to induce MDBs, ways of their visualization and quantification, as well as the possibilities to detect SEK variants in humans are summarized.

  20. Caspase signalling in the absence of apoptosis drives Jnk-dependent invasion.

    PubMed

    Rudrapatna, Vivek A; Bangi, Erdem; Cagan, Ross L

    2013-02-01

    Tumours evolve several mechanisms to evade apoptosis, yet many resected carcinomas show significantly elevated caspase activity. Moreover, caspase activity is positively correlated with tumour aggression and adverse patient outcome. These observations indicate that caspases might have a functional role in promoting tumour invasion and metastasis. Using a Drosophila model of invasion, we show that precise effector caspase activity drives cell invasion without initiating apoptosis. Affected cells express the matrix metalloprotinase Mmp1 and invade by activating Jnk. Our results link Jnk and effector caspase signalling during the invasive process and suggest that tumours under apoptotic stresses from treatment, immune surveillance or intrinsic signals might be induced further along the metastatic cascade.

  1. ERK- and JNK-Dependent Signaling Pathways Contribute to Bombyx mori Nucleopolyhedrovirus Infection▿

    PubMed Central

    Katsuma, Susumu; Mita, Kazuei; Shimada, Toru

    2007-01-01

    Mitogen-activated protein kinases (MAPKs) often play important roles in virus infection. To explore intracellular signaling pathways induced by baculovirus infection, we examined the involvement of MAPKs in Bombyx mori nucleopolyhedrovirus (BmNPV) infection of BmN cells. We found that specific inhibitors of extracellular signal-regulated kinase (ERK) kinase and c-Jun NH2-terminal kinase (JNK) significantly reduced occlusion body (OB) formation and budded virus (BV) production. Next, we quantified OB and BV production after applying the inhibitors at different times postinfection (p.i.). The inhibitors significantly reduced OB and BV production to various extents when applied at 12 h p.i., indicating that the reduction of BmNPV infectivity by these inhibitors occurs at the late stage of infection. Also, we observed that these inhibitors markedly repressed or deregulated the expression of delayed early, late, and very late gene products. Western blot analysis using phospho-MAPK-specific antibodies showed that ERK and JNK were activated at the late stage of BmNPV infection. In addition, the magnitude and pattern of MAPK activation were dependent on the multiplicity of infection. To verify the effects of the inhibitors on BmNPV infection, we also attempted to knock down the B. mori genes BmErk and BmJnk, which encode ERK and JNK, respectively. Knockdown of BmErk and BmJnk resulted in the reduced production of OBs and BVs, confirming that BmERK and BmJNK are involved in the BmNPV infection process. Taken together, these results indicate that the activation of MAPK signaling pathways is required for efficient infection by BmNPV. PMID:17913811

  2. Phosphorylation of PrxII promotes JNK-dependent apoptosis in adult cloned pig kidney.

    PubMed

    Jeon, Young-Joo; Kim, Jumi; Lee, Dong-Seok; Shim, Jung-Hyun; Seo, Kang Seok; Chae, Jung-Il

    2014-08-01

    Organ transplantation is the most effective medical therapy for end-stage renal disease patients; however, there is a critical shortage of human donor organs. Therefore, xenotransplantation using genetically modified cloned porcine kidney is considered as a viable solution, but its fundamental therapeutic mechanism and difference from non-cloned porcine or human kidney for its clinical application is not well known. Here, we performed proteomic analysis to investigate the differentially expressed molecules in kidney tissue obtained from cloned porcine by SCNT, when compared with normal porcine kidney in same age as a control. A total of 80 protein spots were differentially expressed between cloned porcine kidney and control kidney, including apoptotic proteins, structural and anti-oxidant related proteins. Furthermore, very interestingly, the differential expression pattern of PrxII in the cloned porcine kidney was distinguishable from that in the control kidney in terms of the pI and molecular weight. Along with this, apoptotic marker proteins were up-regulated in the cloned porcine kidney. We suggested that these alterations were induced by post-translational modification such as phosphorylation in PrxII and could be mediated by JNK. With this result, we also observed that the down-regulation of JNK activity was caused by blockage of phosphorylation in PrxII T89A region. Taken together, cloned porcine kidney is more susceptible in JNK-induced apoptosis caused by PrxII phosphorylation, in oxidative stress condition. These results will be helpful in the application of cloned porcine xeno-transplants for treating end-stage renal disease patients in a clinical setting. PMID:24909612

  3. Glandular epithelial AR inactivation enhances PTEN deletion-induced uterine pathology.

    PubMed

    Choi, Jaesung Peter; Zheng, Yu; Handelsman, David J; Simanainen, Ulla

    2016-05-01

    Phosphatase and tensin homolog (PTEN) deletion induces uterine pathology, whereas androgen actions via androgen receptor (AR) support uterine growth and therefore may modify uterine cancer risk. We hypothesized that the androgen actions mediated via uterine glandular epithelial AR could modify PTEN deletion-induced uterine pathology. To test our hypothesis, we developed uterine glandular epithelium-specific PTEN and/or AR knockout mouse models comparing the uterine pathology among wild-type (WT), glandular epithelium-specific AR inactivation (ugeARKO), PTEN deletion (ugePTENKO), and the combined PTEN and AR knockout (ugePTENARKO) female mice. The double knockout restricted to glandular epithelium showed that AR inactivation enhanced PTEN deletion-induced uterine pathology with development of intraepithelial neoplasia by 20 weeks of age. In ugePTENARKO, 6/10 (60%) developed intraepithelial neoplasia, whereas 3/10 (30%) developed only glandular hyperplasia in ugePTENKO uterus. No uterine pathology was observed in WT (n=8) and ugeARKO (n=7) uteri. Uterine weight was significantly (P=0.002) increased in ugePTENARKO (374±97 mg (mean±s.e.)) compared with WT (97±6 mg), ugeARKO (94±12 mg), and ugePTENKO (205±33 mg). Estrogen receptor alpha (ERα) and P-AKT expression was modified by uterine pathology but did not differ between ugePTENKO and ugePTENARKO, suggesting that its expressions are not directly affected by androgens. However, progesterone receptor (PR) expression was reduced in ugePTENARKO compared to ugePTENKO uterus, suggesting that PR expression could be regulated by glandular epithelial AR inactivation. In conclusion, glandular epithelial AR inactivation (with persistent stromal AR action) enhanced PTEN deletion-induced uterine pathology possibly by downregulating PR expression in the uterus.

  4. Hydraulic fracture during epithelial stretching

    PubMed Central

    Casares, Laura; Vincent, Romaric; Zalvidea, Dobryna; Campillo, Noelia; Navajas, Daniel; Arroyo, Marino; Trepat, Xavier

    2015-01-01

    The origin of fracture in epithelial cell sheets subject to stretch is commonly attributed to excess tension in the cells’ cytoskeleton, in the plasma membrane, or in cell-cell contacts. Here we demonstrate that for a variety of synthetic and physiological hydrogel substrates the formation of epithelial cracks is caused by tissue stretching independently of epithelial tension. We show that the origin of the cracks is hydraulic; they result from a transient pressure build-up in the substrate during stretch and compression maneuvers. After pressure equilibration cracks heal readily through actomyosin-dependent mechanisms. The observed phenomenology is captured by the theory of poroelasticity, which predicts the size and healing dynamics of epithelial cracks as a function of the stiffness, geometry and composition of the hydrogel substrate. Our findings demonstrate that epithelial integrity is determined in a tension-independent manner by the coupling between tissue stretching and matrix hydraulics. PMID:25664452

  5. Association of Genital Infections Other Than Human Papillomavirus with Pre-Invasive and Invasive Cervical Neoplasia.

    PubMed

    Ghosh, Ishita; Mandal, Ranajit; Kundu, Pratip; Biswas, Jaydip

    2016-02-01

    Human papillomavirus (HPV) is a well-established causative agent of malignancy of the female genital tract and a common Sexually Transmitted Infection. The probable co-factors that prevent spontaneous clearance of HPV and progression to neoplasia are genital tract infections from organisms like Chlamydia, Trichomonas vaginalis etc, smoking, nutritional deficiencies and multiparity. Inflammatory conditions can lead to pre-neoplastic manifestations in the cervical epithelium; however their specific role in cervical carcinogenesis is not yet established. Therefore it is imperative to study the likely association between HPV and co-infection with various common pathogens in the genital tract of women having cervical precancer or cancer. A "Pubmed" search was made for articles in Literature on this topic using the words: Cervical neoplasia, HPV, co-infections, Cervical Intraepithelial Neoplasia (CIN), Trichomonas vaginalis, Candida, Chlamydia and the relevant information obtained was used to draft the review. PMID:27042571

  6. Association of Genital Infections Other Than Human Papillomavirus with Pre-Invasive and Invasive Cervical Neoplasia

    PubMed Central

    Mandal, Ranajit; Kundu, Pratip; Biswas, Jaydip

    2016-01-01

    Human papillomavirus (HPV) is a well-established causative agent of malignancy of the female genital tract and a common Sexually Transmitted Infection. The probable co-factors that prevent spontaneous clearance of HPV and progression to neoplasia are genital tract infections from organisms like Chlamydia, Trichomonas vaginalis etc, smoking, nutritional deficiencies and multiparity. Inflammatory conditions can lead to pre-neoplastic manifestations in the cervical epithelium; however their specific role in cervical carcinogenesis is not yet established. Therefore it is imperative to study the likely association between HPV and co-infection with various common pathogens in the genital tract of women having cervical precancer or cancer. A “Pubmed” search was made for articles in Literature on this topic using the words: Cervical neoplasia, HPV, co-infections, Cervical Intraepithelial Neoplasia (CIN), Trichomonas vaginalis, Candida, Chlamydia and the relevant information obtained was used to draft the review. PMID:27042571

  7. RETROSPECTIVE EVALUATION OF CASES OF NEOPLASIA IN A CAPTIVE POPULATION OF EGYPTIAN FRUIT BATS (ROUSETTUS AEGYPTIACUS).

    PubMed

    Olds, June E; Burrough, Eric R; Fales-Williams, Amanda J; Lehmkuhl, Aaron; Madson, Darin; Patterson, Abby J; Yaeger, Michael J

    2015-06-01

    Reports of neoplasia in Chiroptera species are rare. (6, 10) This retrospective study describes five types of neoplasia identified within a captive population of male Egyptian fruit bats (Rousettus aegyptiacus) housed in a zoo from 2004 through November of 2014. Tumor types identified include fibrosarcoma, cutaneous lymphoma, benign focal bronchioloalveolar neoplasm, anaplastic sarcoma, and sebaceous epithelioma. To the author's knowledge, aside from a recent report of focal brochioloalveolar adenoma, (8) these tumor types have not previously been described in the Rousettus species, nor in chiropterans in general. Based upon these findings and other recent publications regarding R. aegyptiacus, neoplasia does appear to be a significant cause of morbidity and mortality in captive members of this megachiropterid species. PMID:26056887

  8. Gestational trophoblastic neoplasia, an ancient disease: new light and potential therapeutic targets.

    PubMed

    Alazzam, Mo'iad; Tidy, John; Hancock, Barry W; Powers, Hilary

    2010-02-01

    Gestational trophoblastic neoplasia is a rare malignancy, which can occur after any type of pregnancy. The incidence varies according to the geographical location and ethnic origin. Although most patients with gestational trophoblastic neoplasia are cured by conventional chemotherapy and surgery, some suffer resistant disease and may die. New therapeutic agents are needed to reduce the toxicity associated with conventional chemotherapy and treat those with resistant or refractory disease. Molecular targeted treatment provides an exciting avenue, however, the biology of gestational trophoblastic neoplasia is not well understood. This review briefly summarises the recent advances in understanding the pathogenesis and molecular biology of this group of diseases and sheds light on molecules that could provide potential therapeutic targets.

  9. Use of Three-Dimensional Basement Membrane Cultures to Model Oncogene-Induced Changes in Mammary Epithelial Morphogenesis

    PubMed Central

    Mills Shaw, Kenna R.; Wrobel, Carolyn N.; Brugge, Joan S.

    2005-01-01

    The development of breast carcinomas involves a complex set of phenotypic alterations in breast epithelial cells and the surrounding microenvironment. While traditional transformation assays provide models for investigating certain aspects of the cellular processes associated with tumor initiation and progression, they do not model alterations in tissue architecture that are critically involved in tumor development. In this review, we provide examples of how three-dimensional (3D) cell culture models can be utilized to dissect the pathways involved in the development of mammary epithelial structures and to elucidate the mechanisms responsible for oncogene-induced phenotypic alterations in epithelial behavior and architecture. Many normal mammary epithelial cell lines undergo a stereotypic morphogenetic process when grown in the presence of exogenous matrix proteins. This 3D morphogenesis culminates in the formation of well-organized, polarized spheroids, and/or tubules that are highly reminiscent of normal glandular architecture. In contrast, transformed cell lines isolated from mammary tumors exhibit significant deviations from normal epithelial behavior in 3D culture. We describe the use of 3D models as a method for both reconstructing and deconstructing the cell biological and biochemical events involved in mammary neoplasia. PMID:15838601

  10. Development of a Novel Scoring System for Predicting the Risk of Colorectal Neoplasia: A Retrospective Study

    PubMed Central

    2016-01-01

    Objective The purpose of this study was to develop a novel scoring system to screen subjects who have a high risk for colorectal neoplasia. Study Design and Setting We retrospectively analyzed 1061 subjects undergoing total colonoscopy (TCS) for the first time at Gihoku Kosei Hospital. The characteristics and habits of the subjects were analyzed using a multivariate logistic regression analysis. The risk score was established according to each odds ratio of the individual risk factors, and the correlations between the sum of the risk scores and the prevalence of colorectal neoplasia for each individual were evaluated. Results Age 45–59 (risk score: 2 points) and ≥60 (3 points), male gender (1 point), and habitual alcohol consumption ≥21g daily (1 point) were extracted as the significant risk factors for colorectal neoplasia. When the risk groups were determined by summing up these risk scores, the prevalence rates of colorectal neoplasia were 8.8% for the low risk group (0–2 points), 30.5% for the low-moderate risk group (3 points), 39.1% for the high-moderate risk group (4 points), and 57.6% for the high risk group (5 points). In comparison with the low risk group, the odds ratio of the low-moderate risk, the high-moderate risk, and the high risk groups were 4.6, 6.7, and 14.1 folds, respectively. Conclusion Our scoring system, which linearly correlates with the prevalence rate of colorectal neoplasia, may be an effective tool for screening the subjects who have a high risk for colorectal neoplasia. These subjects, therefore, should be recommended to undergo TCS. PMID:27284907

  11. Common Inflammatory Disorders and Neoplasia of the Ileal Pouch: A Review of Histopathology

    PubMed Central

    Gonzalo, David Hernandez; Collinsworth, Amy L.; Liu, Xiuli

    2016-01-01

    Ileal pouch-anal anastomosis (IPAA) is the standard restorative procedure after proctocolectomy in patients with ulcerative colitis (UC) who require colectomy. The ileal pouch is susceptible to a variety of insults including mechanical injury, ischemia, fecal stasis, and infectious agents. In addition, the development of recurrent and idiopathic inflammatory bowel disease and neoplasia may occur in the ileal pouch. Although clinical, endoscopic, and radiographic examination can diagnose many ileal pouch diseases, histologic examination plays an essential role in diagnosis and management, particularly in cases with antibiotic refractory chronic pouchitis and pouch neoplasia. PMID:27785322

  12. Trisomy of the Dscr1 gene suppresses early progression of pancreatic intraepithelial neoplasia driven by oncogenic Kras

    SciTech Connect

    Lee, Jang Choon; Shin, Jimin; Baek, Kwan-Hyuck

    2013-10-11

    Highlights: •A single extra copy of Dscr1 restrains progression of PanIN-1A to PanIN-1B lesions. •Dscr1 trisomy attenuates calcineurin–NFAT pathway in neoplastic ductal epithelium. •Dscr1 trisomy leads to upregulation of p15{sup INK4b} in neoplastic ductal epithelium. •A single extra copy of Dscr1 reduces epithelial proliferation in early PanIN lesions. •Dscr1 trisomy may protect Down syndrome individuals from pancreatic cancer. -- Abstract: Individuals with Down syndrome exhibit remarkably reduced incidence of most solid tumors including pancreatic cancer. Multiple mechanisms arising from the genetic complexity underlying Down syndrome has been suggested to contribute to such a broad cancer protection. In this study, utilizing a genetically engineered mouse model of pancreatic cancer, we demonstrate that trisomy of the Down syndrome critical region-1 (Dscr1), an endogenous calcineurin inhibitor localized on chromosome 21, suppresses the progression of pancreatic intraepithelial neoplasia-1A (PanIN-1A) to PanIN-1B lesions without affecting the initiation of PanIN lesions mediated by oncogenic Kras{sup G12D}. In addition, we show that Dscr1 trisomy attenuates nuclear localization of nuclear factor of activated T-cells (NFAT) accompanied by upregulation of the p15{sup Ink4b} tumor suppressor and reduction of cell proliferation in early PanIN lesions. Our data suggest that attenuation of calcineurin–NFAT signaling in neoplastic pancreatic ductal epithelium by a single extra copy of Dscr1 is sufficient to inhibit the progression of early PanIN lesions driven by oncogenic Kras, and thus may be a potential mechanism underlying reduced incidence of pancreatic cancer in Down syndrome individuals.

  13. Retinal pigment epithelial cell proliferation

    PubMed Central

    Temple, Sally

    2015-01-01

    The human retinal pigment epithelium forms early in development and subsequently remains dormant, undergoing minimal proliferation throughout normal life. Retinal pigment epithelium proliferation, however, can be activated in disease states or by removing retinal pigment epithelial cells into culture. We review the conditions that control retinal pigment epithelial proliferation in culture, in animal models and in human disease and interpret retinal pigment epithelium proliferation in context of the recently discovered retinal pigment epithelium stem cell that is responsible for most in vitro retinal pigment epithelial proliferation. Retinal pigment epithelial proliferation-mediated wound repair that occurs in selected macular diseases is contrasted with retinal pigment epithelial proliferation-mediated fibroblastic scar formation that underlies proliferative vitreoretinopathy. We discuss the role of retinal pigment epithelial proliferation in age-related macular degeneration which is reparative in some cases and destructive in others. Macular retinal pigment epithelium wound repair and regression of choroidal neovascularization are more pronounced in younger than older patients. We discuss the possibility that the limited retinal pigment epithelial proliferation and latent wound repair in older age-related macular degeneration patients can be stimulated to promote disease regression in age-related macular degeneration. PMID:26041390

  14. Thymic carcinoids in multiple endocrine neoplasia type 1.

    PubMed Central

    Teh, B T; Zedenius, J; Kytölä, S; Skogseid, B; Trotter, J; Choplin, H; Twigg, S; Farnebo, F; Giraud, S; Cameron, D; Robinson, B; Calender, A; Larsson, C; Salmela, P

    1998-01-01

    OBJECTIVE: To study the clinical, pathologic, and genetic features of thymic carcinoids in the setting of multiple endocrine neoplasia type 1 (MEN1) and to study means for detection and prevention of this tumor in patients with MEN1. SUMMARY BACKGROUND DATA: Thymic carcinoid is a rare malignancy, with approximately 150 cases reported to date. It may be associated with MEN1 and carries a poor prognosis, with no effective treatment. Its underlying etiology is unknown. METHODS: Ten patients with MEN1 from eight families with anterior mediastinal tumors were included in a case series study at tertiary referring hospitals. Clinicopathologic studies were done on these patients, with a review of the literature. Mutation analysis was performed on the MEN1 gene in families with clusterings of the tumor to look for genotype-phenotype correlation. Loss of heterozygosity was studied in seven cases to look for genetic abnormalities. RESULTS: Histologic studies of all tumors were consistent with the diagnosis of thymic carcinoid. Clustering of this tumor was found in some of the families-three pairs of brothers and three families with first- or second-degree relatives who had thymic carcinoid. All patients described here were men, with a mean age at detection of 44 years (range 31 to 66). Most of the patients had chest pain or were asymptomatic; none had Cushing's or carcinoid syndrome. All tumors were detected by computed tomography (CT) or magnetic resonance imaging (MRI) of the chest. The results of octreoscans performed in three patients were all positive. Histopathologic studies were consistent with the diagnosis of thymic carcinoid and did not stain for ACTH. Mutation analysis of the families with clustering revealed mutations in different exons/introns of the MEN1 gene. Loss of heterozygosity (LOH) studies of seven tumors did not show LOH in the MEN1 region, but two tumors showed LOH in the 1p region. CONCLUSIONS: MEN1-related thymic carcinoids constitute approximately 25

  15. Folate-genetics and colorectal neoplasia: What we know and need to know next

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The metabolism of folate involves a complex network of polymorphic enzymes that may explain a proportion of the risk associated with colorectal neoplasia. Over 60 observational studies primarily in non-Hispanic White populations have been conducted on selected genetic variants in specific genes, MTH...

  16. Neoplasias mielodisplásicas o mieloproliferativas (PDQ®)—Versión para pacientes

    Cancer.gov

    Resumen de información revisada por expertos acerca del tratamiento de las neoplasias mielodisplásicas o mieloproliferativas, incluso las leucemias mielomonocíticas crónicas o juveniles, y la LMC atípica.

  17. Genetics of Endocrine and Neuroendocrine Neoplasias (PDQ®)—Health Professional Version

    Cancer.gov

    Expert-reviewed information summary about the genetics of endocrine and neuroendocrine neoplasias. This summary contains information about the MEN1 gene, the RET gene, genetic testing, and clinical interventions. Psychosocial issues associated with genetic testing and counseling of individuals who may have a hereditary medullary thyroid cancer syndrome are also discussed.

  18. Proceedings From the First Asia-Oceania Research Organisation on Genital Infections and Neoplasia (AOGIN) Meeting

    PubMed Central

    Faro, Edited by Sebastian

    2006-01-01

    The First Asia-Oceania Research Organisation on Genital Infections and Neoplasia (AOGIN) Meeting was held in Kota Kinabalu, Malaysia, in July 2005. The conference covered regional issues relating to infection with the human papillomavirus—epidemiology, virology, and immunology, testing, screening, and prevention strategies—as well as cervical cancer screening and its management.

  19. Local recurrence of pheochromocytoma in multiple endocrine neoplasia type 2A: a diagnostic and therapeutic challenge.

    PubMed

    Tramunt, Blandine; Buffet, Alexandre; Grunenwald, Solange; Vezzosi, Delphine; Bennet, Antoine; Huyghe, Eric; Zerdoud, Slimane; Caron, Philippe

    2016-03-01

    In a patient with multiple endocrine neoplasia type 2A (MEN2A), an inverted physiological ratio between urinary normetanephrines and metanephrines is an early marker of recurrence in epinephrine-secreting pheochromocytoma, and 131I MIBG treatment appears to be a useful therapeutic option in order to avoid multiple invasive surgical procedures in pheochromocytomatosis.

  20. THE INDUCTION OF COLON NEOPLASIA IN MALE RATS EXPOSED TO TRIHALOMETHANES (THMS) IN THE DRINKING WATER

    EPA Science Inventory

    THE INDUCTION OF COLON NEOPLASIA IN MALE RATS EXPOSED TO TRIHALO METHANES (THMs) IN THE DRINKING WATER
    Christopher Sistrunk and Tony DeAngelo, North Carolina Central University and US Environmental Protection Agency
    The THMs are the most widely distributed and the most co...

  1. Brain metastasis from pheochromocytoma in a patient with multiple endocrine neoplasia type 2A.

    PubMed

    Gentile, S; Rainero, I; Savi, L; Rivoiro, C; Pinessi, L

    2001-12-01

    Neurological involvement in multiple endocrine neoplasia (MEN) syndrome is uncommon. Notalgia paresthetica (pruritus localized in an area between D2 and D6 dermatomes) is the neurological symptom more frequently described in patients with MEN 2A. The authors report the unusual case of a MEN 2A patient with a brain metastasis from a pheochromocytoma. PMID:11677427

  2. Elevated expression of ABCB5 in ocular surface squamous neoplasia

    PubMed Central

    Jongkhajornpong, Passara; Nakamura, Takahiro; Sotozono, Chie; Nagata, Maho; Inatomi, Tsutomu; Kinoshita, Shigeru

    2016-01-01

    ATP-binding cassette subfamily B member 5 (ABCB5) is a new member of the ATP-binding cassette superfamily and has been reported as a novel marker for limbal stem cell (LSC), which is essential for corneal homeostasis. ABCB5 expression has also been discovered in the subpopulation of several cancer cells containing the cancer stem cell (CSC). However, the pathogenetic relationship between LSC and CSC and ABCB5 in the ocular surface squamous neoplasm (OSSN) is still entirely unknown. To improve understanding of the role of ABCB5 in OSSN, we performed immunohistochemistry for ABCB5 in nine OSSN case series. While expression of ABCB5 is restricted to the basal epithelial cell layer in the normal limbus, elevated expressions of ABCB5 were clearly observed in all OSSN, and there was some breadth in the range of intensity of ABCB5 expression. Interestingly, the elevated expression patterns of ABCB5 in OSSN could be classified in three categories: perivascular, marginal and diffuse patterns. Our findings demonstrated for the first time that the expression of ABCB5 was upregulated in OSSN and that elevated expression of ABCB5 may be involved in the pathogenesis of OSSN. PMID:26843453

  3. Individual and Complementary Effects of Human Papillomavirus Oncogenes on Epithelial Cell Proliferation and Differentiation.

    PubMed

    Bergner, Sven; Halec, Gordana; Schmitt, Markus; Aubin, François; Alonso, Angel; Auvinen, Eeva

    2016-01-01

    Previous studies on human papillomavirus (HPV) type 16 protein functions have established the oncogenic nature of three viral proteins: E5, E6 and E7. Here we have studied the functions of these proteins by functional deletion of the individual E5, E6 or E7, or both E6 and E7 oncogenes in the context of the whole viral genome. These mutants, or the intact wild-type genome, were expressed from the natural viral promoters along with differentiation of epithelial HaCaT cells in three-dimensional collagen raft cultures. High episomal viral copy numbers were obtained using a transfection-based loxp-HPV16-eGFP-N1 vector system. All epithelial equivalents carrying the different HPV type 16 genomes showed pronounced hyperplastic and dysplastic morphology. Particularly the E7 oncogene, with contribution of E6, was shown to enhance cell proliferation. Specifically, the crucial role of E7 in HPV-associated hyperproliferation was clearly manifested. Based on morphological characteristics, immunohistochemical staining for differentiation and proliferation markers, and low expression of E1^E4, we propose that our raft culture models produce cervical intraepithelial neoplasia (CIN)1 and CIN2-like tissue. Our experimental setting provides an alternative tool to study concerted functions of HPV proteins in the development of epithelial dysplasia. PMID:26636751

  4. Pathogenesis of germ cell neoplasia in testicular dysgenesis and disorders of sex development.

    PubMed

    Jørgensen, Anne; Lindhardt Johansen, Marie; Juul, Anders; Skakkebaek, Niels E; Main, Katharina M; Rajpert-De Meyts, Ewa

    2015-09-01

    Development of human gonads is a sex-dimorphic process which evolved to produce sex-specific types of germ cells. The process of gonadal sex differentiation is directed by the action of the somatic cells and ultimately results in germ cells differentiating to become functional gametes through spermatogenesis or oogenesis. This tightly controlled process depends on the proper sequential expression of many genes and signalling pathways. Disturbances of this process can be manifested as a large spectrum of disorders, ranging from severe disorders of sex development (DSD) to - in the genetic male - mild reproductive problems within the testicular dysgenesis syndrome (TDS), with large overlap between the syndromes. These disorders carry an increased but variable risk of germ cell neoplasia. In this review, we discuss the pathogenesis of germ cell neoplasia associated with gonadal dysgenesis, especially in individuals with 46,XY DSD. We summarise knowledge concerning development and sex differentiation of human gonads, with focus on sex-dimorphic steps of germ cell maturation, including meiosis. We also briefly outline the histopathology of germ cell neoplasia in situ (GCNIS) and gonadoblastoma (GDB), which are essentially the same precursor lesion but with different morphological structure dependent upon the masculinisation of the somatic niche. To assess the risk of germ cell neoplasia in different types of DSD, we have performed a PubMed search and provide here a synthesis of the evidence from studies published since 2006. We present a model for pathogenesis of GCNIS/GDB in TDS/DSD, with the risk of malignancy determined by the presence of the testis-inducing Y chromosome and the degree of masculinisation. The associations between phenotype and the risk of neoplasia are likely further modulated in each individual by the constellation of the gene polymorphisms and environmental factors.

  5. Distribution of human papillomavirus genotypes among cervical intraepithelial neoplasia and invasive cancers in Macao.

    PubMed

    Hlaing, Thazin; Yip, Yuk-Ching; Ngai, Karry L K; Vong, Heong-Ting; Wong, Sio-In; Ho, Wendy C S; Batalha, Sellma L S C; Chan, Paul K S

    2010-09-01

    Macao is a densely populated city situated in East Asia where a relatively high prevalence of human papillomavirus (HPV) types 52 and 58 has been reported in women with invasive cervical cancer. To provide data for a population-specific estimation on the impact of HPV vaccines, paraffin-embedded tissues collected from women with invasive cervical cancer or cervical intrapeitheilal neoplasia grade 2 or 3 confirmed histologically were examined for HPV using the INNO-LiPa kit. Of the 35 HPV-positive patients with invasive cancer, one HPV type was detected in 68.6%, and 31.4% were co-infected with more than one HPV type. Overall, HPV 16, HPV 18, HPV 52, and HPV 54 were the most common types found respectively in 57.1%, 17%, 11.4%, and 8.5% of patients with invasive cervical cancer. Among the 59 HPV-positive patients with cervical intraepithelial neoplasia grade 2/3, 55.9% hardbored one HPV type, and 44.1% had co-infections. The common HPV types found included HPV 16 (52.5%), HPV 52 (23.7%), HPV 58 (18.7%), and HPV 33 (17%). Although HPV 11 (a low-risk type) was also found commonly in invasive cervical cancers (14.3%) and cervical intraepithelial neoplasia grade 2/3 (15.3%), the fact that they all existed as co-infections with another high-risk type suggested HPV 11 was not the cause of the lesion. The current vaccines targeting HPV 16/18 are expected to cover 62.9-74.3% of invasive cervical cancers and 32.2-55.9% of cervical intraepithelial neoplasia 2/3 in Macao. Widespread HPV vaccination is expected to reduce substantially the disease burden associated with cervical neoplasia in Macao.

  6. Epithelial Sodium Channels in Pulmonary Epithelial Progenitor and Stem Cells

    PubMed Central

    Liu, Yang; Jiang, Bi-Jie; Zhao, Run-Zhen; Ji, Hong-Long

    2016-01-01

    Regeneration of the epithelium of mammalian lungs is essential for restoring normal function following injury, and various cells and mechanisms contribute to this regeneration and repair. Club cells, bronchioalveolar stem cells (BASCs), and alveolar type II epithelial cells (ATII) are dominant stem/progenitor cells for maintaining epithelial turnover and repair. Epithelial Na+ channels (ENaC), a critical pathway for transapical salt and fluid transport, are expressed in lung epithelial progenitors, including club and ATII cells. Since ENaC activity and expression are development- and differentiation-dependent, apically located ENaC activity has therefore been used as a functional biomarker of lung injury repair. ENaC activity may be involved in the migration and differentiation of local and circulating stem/progenitor cells with diverse functions, eventually benefiting stem cells spreading to re-epithelialize injured lungs. This review summarizes the potential roles of ENaC expressed in native progenitor and stem cells in the development and regeneration of the respiratory epithelium. PMID:27570489

  7. Epithelial Sodium Channels in Pulmonary Epithelial Progenitor and Stem Cells.

    PubMed

    Liu, Yang; Jiang, Bi-Jie; Zhao, Run-Zhen; Ji, Hong-Long

    2016-01-01

    Regeneration of the epithelium of mammalian lungs is essential for restoring normal function following injury, and various cells and mechanisms contribute to this regeneration and repair. Club cells, bronchioalveolar stem cells (BASCs), and alveolar type II epithelial cells (ATII) are dominant stem/progenitor cells for maintaining epithelial turnover and repair. Epithelial Na(+) channels (ENaC), a critical pathway for transapical salt and fluid transport, are expressed in lung epithelial progenitors, including club and ATII cells. Since ENaC activity and expression are development- and differentiation-dependent, apically located ENaC activity has therefore been used as a functional biomarker of lung injury repair. ENaC activity may be involved in the migration and differentiation of local and circulating stem/progenitor cells with diverse functions, eventually benefiting stem cells spreading to re-epithelialize injured lungs. This review summarizes the potential roles of ENaC expressed in native progenitor and stem cells in the development and regeneration of the respiratory epithelium. PMID:27570489

  8. Integrins and epithelial cell polarity

    PubMed Central

    Lee, Jessica L.; Streuli, Charles H.

    2014-01-01

    ABSTRACT Cell polarity is characterised by differences in structure, composition and function between at least two poles of a cell. In epithelial cells, these spatial differences allow for the formation of defined apical and basal membranes. It has been increasingly recognised that cell–matrix interactions and integrins play an essential role in creating epithelial cell polarity, although key gaps in our knowledge remain. This Commentary will discuss the mounting evidence for the role of integrins in polarising epithelial cells. We build a model in which both inside-out signals to polarise basement membrane assembly at the basal surface, and outside-in signals to control microtubule apical–basal orientation and vesicular trafficking are required for establishing and maintaining the orientation of epithelial cell polarity. Finally, we discuss the relevance of the basal integrin polarity axis to cancer. This article is part of a Minifocus on Establishing polarity. For further reading, please see related articles: ‘ERM proteins at a glance’ by Andrea McClatchey (J. Cell Sci. 127, 3199–3204). ‘Establishment of epithelial polarity – GEF who's minding the GAP?’ by Siu Ngok et al. (J. Cell Sci. 127, 3205–3215). PMID:24994933

  9. Circulating Cytokines and Nitric Oxide are Involved in the Inhibition of Neutrophil Migration in Patients with Uterine Cervical Neoplasia

    PubMed Central

    Micheli, Douglas Côbo; Fernandes, Paulo Cesar; Cruvinel, João Celso Garcia; Nomelini, Isabela Destro; Murta, Eddie Fernando Candido; Tavares-Murta, Beatriz Martins

    2012-01-01

    Aim To verify if patients with cervical neoplasia produce mediators that reduce leukocyte function. Methods Control neutrophils incubated with normal serum or serum from pre-invasive or invasive neoplasia patients were assayed for chemotaxis. Mediators were assayed in serum and in leukocyte supernatants. Experiments were also performed in random patients after surgery. Results Neutrophils incubated with patient sera, but not normal sera, failed to migrate towards the chemoattractants. In invasive neoplasia compared to controls, IL-6 and IL-8, and IL-10 and TNF-α were elevated in serum and in neutrophil supernatants, respectively. Nitrite levels were elevated in mononuclear cell supernatants from patients than controls. After surgery, serum cytokine levels were reduced, mainly in pre-invasive patients. Neutrophils treated with serum from pre-invasive patients undergone surgery had restored migration. Conclusion Patients with cervical neoplasia produce mediators, predominantly induced by tumor cells, able to impair the inflammatory response at very early stages of disease. PMID:22693424

  10. Neoplasias mieloproliferativas y síndromes mielodisplásicos—Versión para profesionales de salud

    Cancer.gov

    Información del Instituto Nacional del Cáncer para profesionales de salud sobre el tratamiento de las neoplasias mieloproliferativas, así como referencias a estudios clínicos y otros temas relacionados.

  11. Increased activity of 6-phosphogluconate dehydrogenase and glucose-6-phosphate dehydrogenase in purified cell suspensions and single cells from the uterine cervix in cervical intraepithelial neoplasia.

    PubMed Central

    Jonas, S. K.; Benedetto, C.; Flatman, A.; Hammond, R. H.; Micheletti, L.; Riley, C.; Riley, P. A.; Spargo, D. J.; Zonca, M.; Slater, T. F.

    1992-01-01

    The activities of 6-phosphogluconate dehydrogenase and glucose-6-phosphate dehydrogenase have been measured in squamous epithelial cells of the uterine cervix from normal patients and cases of cervical intraepithelial neoplasia (CIN). A biochemical cycling method, which uses only simple equipment and is suited to routine use and to automation, was applied to cells separated by gradient centrifugation. In addition, cells were examined cytochemically, and the intensity of staining in the cytoplasm of single whole cells was measured using computerised microcytospectrophotometry. Twenty per cent of cells in samples from normal patients (n=61) showed staining intensities above an extinction of 0.15 at 540 nm, compared to 71% of cases of CIN 1 (n=14), 91% of cases of CIN 2 (n=11) and 67% of cases of CIN 3 (n=15). The cytochemical data do not allow definitive distinctions to be made between different grades of CIN whereas the biochemical assay applied to cell lysates shows convincing differences between normal samples and cases of CIN. There are no false negatives for CIN 3 (n=14) and CIN 2 (n=10) and 11% false negatives for CIN 1 (n=9) and 14% of false positives for normal cases (n=21). The results of this preliminary study with reference to automation are discussed [corrected]. Images Figure 1 PMID:1637668

  12. NME genes in epithelial morphogenesis

    PubMed Central

    2012-01-01

    The NME family of genes encodes highly conserved multifunctional proteins that have been shown to participate in nucleic acid metabolism, energy homeostasis, cell signaling, and cancer progression. Some family members, particularly isoforms 1 and 2, have attracted extensive interests because of their potential anti-metastasis activity. Unfortunately, there have been few consensus mechanistic explanations for this critical function because of the numerous molecular functions ascribed to these proteins, including nucleoside diphosphate kinase, protein kinase, nuclease, transcription factor, growth factor, among others. In addition, different studies showed contradictory prognostic correlations between NME expression levels and tumor progression in clinical samples. Thus, analyses using pliable in vivo systems have become critical for unraveling at least some aspects of the complex functions of this family of genes. Recent works using the Drosophila genetic system have suggested a role for NME in regulating epithelial cell motility and morphogenesis, which has also been demonstrated in mammalian epithelial cell culture. This function is mediated by promoting internalization of growth factor receptors in motile epithelial cells, and the adherens junction components such as E-cadherin and β-catenin in epithelia that form the tissue linings. Interestingly, NME genes in epithelial cells appear to function in a defined range of expression levels. Either down-regulation or over-expression can perturb epithelial integrity, resulting in different aspects of epithelial abnormality. Such biphasic functions provide a plausible explanation for the documented anti-metastatic activity and the suspected oncogenic function. This review summarizes these recent findings and discusses their implications. PMID:21336542

  13. Ion Channels in Epithelial Cells

    NASA Astrophysics Data System (ADS)

    Palmer, Lawrence G.

    Ion channels in epithelial cells serve to move ions, and in some cases fluid, between compartments of the body. This function of the transfer of material is fundamentally different from that of the transfer of information, which is the main job of most channels in excitable cells. Nevertheless the basic construction of the channels is similar in many respects in the two tissue types. This chapter reviews the nature of channels in epithelia and discusses how their functions have evolved to accomplish the basic tasks for which they are responsible. I will focus on three channel types: epithelial Na+ channels, inward-rectifier K+ channels, and CFTR Cl- channels.

  14. Multiple endocrine neoplasia, type II: a combined surgical and genetic approach to treatment.

    PubMed Central

    Partington, M W; Ghent, W R; Sears, E V; Simpson, N E

    1981-01-01

    A family with multiple endocrine neoplasia, type II living in southeastern Ontario is described. Twenty individuals are known to have had medullary carcinoma of the thyroid, pheochromocytoma or both, the diagnosis of multiple endocrine neoplasia. type II is strongly suspected in five other individuals in the earlier generations. In this family the diseases seems to be transmitted by an autosomal dominant gene. A screening program set up for the family in 1977 has in 2 years identified four asymptomatic individuals (three with medullary carcinoma of the thyroid and one with this carcinoma and a pheochromocytoma). The family background, clinical picture, treatment and some of the problems of the screening program are described. PMID:7214269

  15. Inhibition of benzo(a)pyrene-induced mouse forestomach neoplasia by dietary soy sauce

    SciTech Connect

    Benjamin, H.; Storkson, J.M.; Nagahara, A.; Pariza, M.W. )

    1991-03-15

    Japanese-style fermented soy sauce (shoyu) contains anticarcinogenic activity. ICR mice were fed a semi-purified diet containing shoyu. 2 wks later a regimen consisting of 2 doses (p.o.) of benzo(a)pyrene per wk for 4 wks was begun, to initiate forestomach neoplasia. 23 wks later the animals were sacrificed, forestomach neoplasms counted and histologically confirmed. Shoyu produced a significant dose-dependent reduction in neoplasms, which appeared maximal when shoyu was present at 20% of the diet. Exposure to nitrite neither enhanced nor diminished the anticarcinogenic effect. Shoyu was found to contain antioxidant activity which may be related to the observed anticarcinogenic effect. Surprisingly mouse forestomach ornithine decarboxylase (ODC) activity was induced by shoyu, due in part to high sodium chloride content. Since ODC induction appears to be an early and possibly obligatory event in tumor promotion, the inhibition of neoplasia by shoyu probably occurs at a later step.

  16. Immunomodulatory effects of alpha interferon and thymostimulin in patients with neoplasias.

    PubMed Central

    Munno, I; Marinaro, M; Gesario, A; Cannuscio, B; Michel, Y; Paulling, E

    1995-01-01

    In this report, we have evaluated the immunological effects following administration of alpha interferon (IFN-alpha) in combination with thymostimulin (TP-1), as well as of IFN-alpha and TP-1 alone in patients with neoplasias who underwent surgery and were subsequently treated with conventional chemotherapy. Data suggest that the combination of IFN-alpha and TP-1 is the most effective in the up-regulation of some immune parameters such as the CD4(+)-CD8+ cell-dependent antibacterial activity. Since this immune function plays an important role in the host protection against different targets such as invading microorganisms and/or neoplastic cells, the administration of TP-1-IFN-alpha is advisable for patients with neoplasias under chemotherapy. PMID:7583935

  17. Endoscopic Mucosal Resection in the Management of Esophageal Neoplasia: Current Status and Future Directions

    PubMed Central

    Namasivayam, Vikneswaran; Wang, Kenneth K.; Prasad, Ganapathy A

    2010-01-01

    Endoscopic mucosal resection has expanded the role of the gastroenterologist in the management of esophageal neoplasia from screening and diagnosis to staging and endoscopic treatment. Its rise to prominence is a reflection of the long identified need to obtain histological information regarding depth of invasion and neoplastic margins during therapy that previously could not be achieved with ablative techniques. The resultant improvement in diagnosis and staging has allowed for better selection of patients for endoscopic therapy who may be spared invasive surgery. The clinical indications, endoscopic techniques, outcomes and complications in the management of esophageal neoplasia are reviewed in this manuscript. Training requirements to achieve proficiency in EMR as well as potential quality measures to assess competence are also proposed in this review. PMID:20541628

  18. Abraham Lincoln's marfanoid mother: the earliest known case of multiple endocrine neoplasia type 2B?

    PubMed

    Sotos, John G

    2012-07-01

    The nature and cause of President Abraham Lincoln's unusual physical features have long been debated, with the greatest attention directed at two monogenic disorders of the transforming growth factor β system: Marfan syndrome and multiple endocrine neoplasia type 2B. The present report examines newly discovered phenotypic information about Lincoln's biological mother, Nancy Hanks Lincoln, and concludes that (a) Lincoln's mother was skeletally marfanoid, (b) the President and his mother were highly concordant for the presence of numerous facial features found in various transforming growth factor β disorders, and (c) Lincoln's mother, like her son, had hypotonic skeletal muscles, resulting in myopathic facies and 'pseudodepression'. These conclusions establish that mother and son had the same monogenic autosomal dominant marfanoid disorder. A description of Nancy Hanks Lincoln as coarse-featured, and a little-known statement that a wasting disease contributed to her death at age 34, lends support to the multiple endocrine neoplasia type 2B hypothesis.

  19. Neoplasia in felids at the Knoxville Zoological Gardens, 1979-2003.

    PubMed

    Owston, Michael A; Ramsay, Edward C; Rotstein, David S

    2008-12-01

    A review of medical records and necropsy reports from 1979-2003 found 40 neoplasms in 26 zoo felids, including five lions (Panthera leo, two males and three females), three leopards (Panthera pardus, two males and one female), one jaguar (Panthera onca, female), 11 tigers (Panthera tigris, three males and eight females), two snow leopards (Panthera uncia, one male and one female), two cougars (Felis concolor, one male and one female), one bobcat (Felis rufus, male), and one cheetah (Acinonyx jubatus, female). Animals that had not reached 3 yr of age or had been housed in the collection less than 3 yrs were not included in the study. Neoplasia rate at necropsy was 51% (24/47), and overall incidence of felid neoplasia during the study period was 25% (26/103). Neoplasia was identified as the cause of death or reason for euthanasia in 28% (13/47) of those necropsied. Neoplasms were observed in the integumentary-mammary (n=11), endocrine (n=10), reproductive (n=8), hematopoietic-lymphoreticular (n=5), digestive (n=3), and hepatobiliary (n=2) systems. One neoplasm was unclassified by system. Multiple neoplasms were observed in 11 animals. Both benign and malignant neoplasms were observed in all systems except for the hematopoietic-lymphoreticular systems where all processes were malignant. Of the endocrine neoplasms, those involving the thyroid and parathyroid glands predominated (n=8) over other endocrine organs and included adenomas and carcinomas. In the integumentary system, 63% (7/11) of neoplasms involved the mammary gland, with mammary carcinoma representing 83% (6/7) of the neoplasms. The rates of neoplasia at this institution, during the given time period, appears to be greater than rates found in the one other published survey of captive felids.

  20. Neoplasia in felids at the Knoxville Zoological Gardens, 1979-2003.

    PubMed

    Owston, Michael A; Ramsay, Edward C; Rotstein, David S

    2008-12-01

    A review of medical records and necropsy reports from 1979-2003 found 40 neoplasms in 26 zoo felids, including five lions (Panthera leo, two males and three females), three leopards (Panthera pardus, two males and one female), one jaguar (Panthera onca, female), 11 tigers (Panthera tigris, three males and eight females), two snow leopards (Panthera uncia, one male and one female), two cougars (Felis concolor, one male and one female), one bobcat (Felis rufus, male), and one cheetah (Acinonyx jubatus, female). Animals that had not reached 3 yr of age or had been housed in the collection less than 3 yrs were not included in the study. Neoplasia rate at necropsy was 51% (24/47), and overall incidence of felid neoplasia during the study period was 25% (26/103). Neoplasia was identified as the cause of death or reason for euthanasia in 28% (13/47) of those necropsied. Neoplasms were observed in the integumentary-mammary (n=11), endocrine (n=10), reproductive (n=8), hematopoietic-lymphoreticular (n=5), digestive (n=3), and hepatobiliary (n=2) systems. One neoplasm was unclassified by system. Multiple neoplasms were observed in 11 animals. Both benign and malignant neoplasms were observed in all systems except for the hematopoietic-lymphoreticular systems where all processes were malignant. Of the endocrine neoplasms, those involving the thyroid and parathyroid glands predominated (n=8) over other endocrine organs and included adenomas and carcinomas. In the integumentary system, 63% (7/11) of neoplasms involved the mammary gland, with mammary carcinoma representing 83% (6/7) of the neoplasms. The rates of neoplasia at this institution, during the given time period, appears to be greater than rates found in the one other published survey of captive felids. PMID:19110704

  1. Cloning and characterization of neoplasia-related genes in flat oyster Ostrea edulis.

    PubMed

    Martín-Gómez, Laura; Villalba, Antonio; Carballal, María Jesús; Abollo, Elvira

    2014-04-01

    Bonamiosis and disseminated neoplasia (DN) are the most important diseases affecting cultured flat oysters Ostrea edulis in Galicia (NW Spain). Previous research using suppresive substraction hybridisation that had been performed addressing the molecular basis of DN as well as the induction and development of the disease in oysters, yielded the whole open reading frame of nine genes: XBP-1, RACK, NDPk, C1qTNF, RPA3, SAP18, p23, ubiquitin and ferritin. These nine genes were characterized in this study. The phylogenetic relationships for each gene were studied using minimum-evolution methods. Quantitative-PCR assays were also developed to analyse the modulation of the expression of these genes by bonamiosis and disseminated neoplasia. Gene expression profiles were studied in haemolymph cells and in various organs (gill, gonad, mantle and digestive gland) of oysters affected by bonamiosis, disseminated neoplasia, both diseases and in non-affected oysters (control). The expression of XBP-1, NDPk, RPA3, SAP18 and ferritin increased in haemolymph cells of oysters with heavy bonamiosis. The expression of C1qTNF; SAP18 and p23 increased in haemolymph cells of oysters with DN. The expression of XBP-1, RACK, NDPk, RPA3 and p23 significantly increased in haemolymph cells of oysters affected by both diseases. There were changes in the expression of a number of genes in different organs depeding on disease stage: RACK expression increased in gills of oysters with bonamiosis, XBP-1 increased in mantle and digestive organs of oysters with light DN and RPA3 expression increased in gonads of oysters with heavy bonamiosis and heavy neoplasia. PMID:24560728

  2. Notalgia Paresthetica and Multiple Endocrine Neoplasia Syndrome 2A: A Case Report.

    PubMed

    Alcántara, Francisco; Feito, Marta; Albizuri, Fátima; Beato, María; De Lucas, Raúl

    2016-09-01

    Notalgia paresthetica is characterized by a hyperpigmented macular pruritic skin lesion most commonly localized unilaterally in the middle and upper back region. This condition has been reported in association with multiple endocrine neoplasia syndrome type 2A (MEN 2A) in several families; it rarely affects children and it may serve as an early marker of MEN 2A. We report a 9-year-old girl diagnosed with MEN 2A and notalgia paresthetica. PMID:27396529

  3. Clonal Evolution in Two Patients with Autoimmune Disease and Lymphoreticular Neoplasia

    PubMed Central

    Adam, M.; Thorburn, Marigold J.; Gibbs, W. N.; Brooks, S. E. H.; Hanchard, B.

    1970-01-01

    Two cases are described, one with proven lymphosarcoma and doubtful autoimmune disease, and the second with the reverse situation, in which circulating abnormal mononuclear cells showed PHA responsiveness and an abnormal chromosomal constitution (clonal evolution). These findings are discussed in the light of previous cytogenetic studies of lymphoreticular neoplasia and autoimmune disease and the relationship between these two conditions. ImagesFigs. 2-3Fig. 9Fig. 4Figs. 6-7Figs. 1,5Fig. 8 PMID:4393772

  4. Turner syndrome and meningioma: support for a possible increased risk of neoplasia in Turner syndrome.

    PubMed

    Pier, Danielle B; Nunes, Fabio P; Plotkin, Scott R; Stemmer-Rachamimov, Anat O; Kim, James C; Shih, Helen A; Brastianos, Priscilla; Lin, Angela E

    2014-01-01

    Neoplasia is uncommon in Turner syndrome, although there is some evidence that brain tumors are more common in Turner syndrome patients than in the general population. We describe a woman with Turner syndrome (45,X) with a meningioma, in whom a second neoplasia, basal cell carcinomas of the scalp and nose, developed five years later in the absence of therapeutic radiation. Together with 7 cases of Turner syndrome with meningioma from a population-based survey in the United Kingdom, and 3 other isolated cases in the literature, we review this small number of patients for evidence of risk factors related to Turner syndrome, such as associated structural anomalies or prior treatment. We performed histological and fluorescent in situ hybridization (FISH) of 22q (NF2 locus) analyses of the meningeal tumor to search for possible molecular determinants. We are not able to prove causation between these two entities, but suggest that neoplasia may be a rare associated medical problem in Turner syndrome. Additional case reports and extension of population-based studies are needed.

  5. Inflammation and Atrophy Precede Prostate Neoplasia in PhIP Induced Rat Model

    SciTech Connect

    Borowsky, A D; Dingley, K; Ubick, E; Turteltaub, K; Cardiff, R D; DeVere-White, R

    2006-06-01

    2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP) has been implicated as a major mutagenic heterocyclic amine in the human diet and is carcinogenic in the rat prostate. In order to validate PhIP induced rat prostate neoplasia as a model of human prostate cancer progression, we sought to study the earliest histologic and morphologic changes in the prostate and to follow the progressive changes over time. We fed 67 male Fischer F344 5 week old rats with PhIP (400 PPM) or control diets for 20 weeks, and then sacrificed animals for histomorphologic examination at age 25 weeks, 45 weeks, and 65 weeks. Animals treated with PhIP showed significantly more inflammation (P=.002 (25wk), >.001(45wk), .016(65wk)) and atrophy (P=.003(25wk), >.001(45wk), .006 (65wk)) in their prostate glands relative to controls. Prostatic intraepithelial neoplasia (PIN) occurred only in PhIP treated rats. PIN lesions arose in areas of glandular atrophy, most often in the ventral prostate. Atypical cells in areas of atrophy show loss of glutathione S-transferase pi immunostaining preceding development of PIN. None of the animals in this study developed invasive carcinomas differing from previous reports. Overall, these findings suggest that the pathogenesis of prostatic neoplasia in the PhIP treated rat prostate proceeds from inflammation to post-inflammatory proliferative atrophy to PIN.

  6. Recessive transmission of a multiple endocrine neoplasia syndrome in the rat.

    PubMed

    Fritz, Andreas; Walch, Axel; Piotrowska, Kamilla; Rosemann, Michael; Schäffer, Ekkehard; Weber, Karin; Timper, Andreas; Wildner, Gerhild; Graw, Jochen; Höfler, Heinz; Atkinson, Michael J

    2002-06-01

    We describe a novel hereditary cancer syndrome in the rat that is transmitted by a recessive gene mutation. Animals exhibiting the mutant phenotype develop multiple neuroendocrine malignancies within the first year of life. The endocrine neoplasia is characterized by bilateral adrenal pheochromocytoma, multiple extra-adrenal pheochromocytoma, bilateral medullary thyroid cell neoplasia, bilateral parathyroid hyperplasia, and pituitary adenoma. The appearance of neoplastic disease is preceded by the development of bilateral juvenile cataracts. Although the spectrum of affected tissues is reminiscent of human forms of multiple endocrine neoplasia (MEN), no germ-line mutations were detected in the Ret or Menin genes that are responsible for the dominantly inherited MEN syndromes in humans. Segregation studies in F1 and F2 crosses yielded frequencies of affected animals entirely consistent with a recessive autosomal mode of inheritance. The lack of the phenotype in F1 animals effectively excludes a germ-line tumor suppressor gene mutation as the causal event. The absence of mutation of known MEN genes and the unique constellation of affected tissues, plus the recessive mode of inheritance, lead us to conclude that the mutation of an as yet unknown gene is responsible for this syndrome of inherited neuroendocrine cancer.

  7. Endoscopic submucosal dissection of colorectal neoplasia located on the suture line of anastomosis.

    PubMed

    Horii, Joichiro; Uraoka, Toshio; Goto, Osamu; Ishii, Hiroyuki; Shimoda, Masayuki; Yahagi, Naohisa

    2014-08-01

    Although endoscopic submucosal dissection (ESD) can remove gastrointestinal neoplasia even with severe fibrosis into the submucosa, the safety and efficacy of ESD for colorectal neoplasia (CRN) located on the suture line of anastomosis (SLA) has not been assessed. The aim of this study was to evaluate the feasibility of ESD for CRN located on the SLA, performed by a highly skilled endoscopist. Three consecutive patients with CRN located on the SLA were treated with ESD. In all cases, ESD was safely performed without any adverse events. The median tumor size of the resected CRN was 30 mm (range 12-75 mm) and the median procedure time was 150 min (range 50-150 min). Curative resection was achieved in two cases without local recurrence during a 12-month observation period. In one case, the CRN were resected in an almost en bloc fashion, but a decision was made to spare the edge of the CRN that was directly on the SLA in order to avoid delayed perforation, and this edge was instead removed with hemostatic forceps. Although the surveillance colonoscopy revealed a small residual neoplasia, it was curatively treated by endoscopically. In all cases, ESD managed to avoid the need for repetitive surgery. This case series suggests the feasibility of ESD performed by a highly skilled endoscopist as a curative treatment for the CRN located on the SLA.

  8. (1)H NMR Spectroscopy of Fecal Extracts Enables Detection of Advanced Colorectal Neoplasia.

    PubMed

    Amiot, Aurelien; Dona, Anthony C; Wijeyesekera, Anisha; Tournigand, Christophe; Baumgaertner, Isabelle; Lebaleur, Yann; Sobhani, Iradj; Holmes, Elaine

    2015-09-01

    Colorectal cancer (CRC) is a growing cause of mortality in developing countries, warranting investigation into its etiopathogenesis and earlier diagnosis. Here, we investigated the fecal metabolic phenotype of patients with advanced colorectal neoplasia and controls using (1)H-nuclear magnetic resonance (NMR) spectroscopy and multivariate modeling. The fecal microbiota composition was assessed by quantitative real-time PCR as well as Wif-1 methylation levels in stools, serum, and urine and correlated to the metabolic profile of each patient. The predictivity of the model was 0.507 (Q(2)Y), and the explained variance was 0.755 (R(2)Y). Patients with advanced colorectal neoplasia demonstrated increased fecal concentrations of four short-chain fatty acids (valerate, acetate, propionate, and butyrate) and decreased signals relating to β-glucose, glutamine, and glutamate. The predictive accuracy of the multivariate (1)H NMR model was higher than that of the guaiac-fecal occult blood test and the Wif-1 methylation test for predicting advanced colorectal neoplasia. Correlation analysis between fecal metabolites and bacterial profiles revealed strong associations between Faecalibacterium prausnitzii and Clostridium leptum species with short-chain fatty acids concentration and inverse correlation between Faecalibacterium prausnitzii and glucose. These preliminary results suggest that fecal metabonomics may potentially have a future role in a noninvasive colorectal screening program and may contribute to our understanding of the role of these dysregulated molecules in the cross-talk between the host and its bacterial microbiota.

  9. Identifying constituent spectra sources in multispectral images to quantify and locate cervical neoplasia

    NASA Astrophysics Data System (ADS)

    Baker, Kevin C.; Bambot, Shabbir

    2011-02-01

    Optical spectroscopy has been shown to be an effective method for detecting neoplasia. Guided Therapeutics has developed LightTouch, a non invasive device that uses a combination of reflectance and fluorescence spectroscopy for identifying early cancer of the human cervix. The combination of the multispectral information from the two spectroscopic modalities has been shown to be an effective method to screen for cervical cancer. There has however been a relative paucity of work in identifying the individual spectral components that contribute to the measured fluorescence and reflectance spectra. This work aims to identify the constituent source spectra and their concentrations. We used non-negative matrix factorization (NNMF) numerical methods to decompose the mixed multispectral data into the constituent spectra and their corresponding concentrations. NNMF is an iterative approach that factorizes the measured data into non-negative factors. The factors are chosen to minimize the root-mean-squared residual error. NNMF has shown promise for feature extraction and identification in the fields of text mining and spectral data analysis. Since both the constituent source spectra and their corresponding concentrations are assumed to be non-negative by nature NNMF is a reasonable approach to deconvolve the measured multispectral data. Supervised learning methods were then used to determine which of the constituent spectra sources best predict the amount of neoplasia. The constituent spectra sources found to best predict neoplasia were then compared with spectra of known biological chromophores.

  10. Correlation between Helicobacter pylori-associated gastric diseases and colorectal neoplasia

    PubMed Central

    Qing, Ying; Wang, Min; Lin, Ying-Min; Wu, Dong; Zhu, Jing-Yu; Gao, Lang; Liu, Yan-Yan; Yin, Teng-Fei

    2016-01-01

    AIM: To explore the correlation between Helicobacter pylori (H. pylori)-associated gastric diseases and colorectal neoplasia. METHODS: Patients included in this study underwent a colonoscopy and esophago-gastro-duodenoscopy (EGD) along with histopathological measurement between March 2012 and March 2015 at Qi-Lu Hospital of Shandong University, who also had results of H. pylori detection. A total of 233 cases were selected. Demographic data, H. pylori infection status (including results of rapid urease tests and gastric mucosa pathological examinations) and histopathological examination results of gastric and colorectal mucosa were gathered and analyzed. The statistical analysis focused on the prevalence of colorectal neoplasms among patients with various histopathological categories of the stomach. ORs and their 95%CI were calculated to describe the strengths of the associations. RESULTS: The incidence rates of colorectal adenoma without high-grade intraepithelial neoplasia (HGIEN) (OR = 2.400, 95%CI: 0.969-5.941), adenoma with HGIEN (5.333, 1.025-27.758) and adenocarcinoma (1.455, 0.382-5.543) were all higher for patients with H. pylori-associated gastritis than for those in the control group. The incidence rate of colorectal adenoma with HGIEN (3.218, 0.767-13.509) was higher in patients with intestinal metaplasia than in the control group, while the incidence rates of adenoma without HGIEN (0.874, 0.414-1.845) and adenocarcinoma (0.376, 0.096-1.470) were lower in the intestinal metaplasia group than in the control group. The incidence rate of colorectal adenoma without HGIEN (3.111, 1.248-7.753) was significantly higher in the gastric intraepithelial neoplasia group than in the control group, while the rates of adenoma with HGIEN (1.481, 0.138-15.941) and adenocarcinoma (2.020, 0.561-7.272) were higher in the gastric intraepithelial neoplasia group. Incidence rates of colorectal adenoma without HGIEN (1.067, 0.264-4.314), adenoma with HGIEN (2.667, 0

  11. Collagenous gastritis: a long-term follow-up with the development of endocrine cell hyperplasia, intestinal metaplasia, and epithelial changes indeterminate for dysplasia.

    PubMed

    Winslow, J L; Trainer, T D; Colletti, R B

    2001-11-01

    This report reviews the literature pertaining to collagenous gastritis and describes the clinicopathologic evolution of this disease in a patient during a 12-year period. We examined 109 biopsy specimens of gastric mucosa from 19 different endoscopic procedures for the severity and distribution of collagenous gastritis in a single patient. Assessments were undertaken for the presence of endocrine and gastrin cell hyperplasias and dysplastic epithelial changes. Relative to biopsy specimens from age- and sex-matched control subjects, the patient's biopsy specimens showed a significantly lower number of antral gastrin cells, along with a significant corpus endocrine cell hyperplasia, suggesting an increased risk of endocrine neoplasia. Gastric corpus biopsy specimens revealed an active, chronic gastritis, subepithelial collagen deposition, smooth muscle hyperplasia, and mild to moderate glandular atrophy. Additional findings of intestinal metaplasia and reactive epithelial changes indeterminate for dysplasia raise concerns about the potential for adenocarcinoma. PMID:11710694

  12. MicroRNAs and Epithelial Immunity

    PubMed Central

    Liu, Jun; Drescher, Kristen M.; Chen, Xian-Ming

    2009-01-01

    MicroRNAs are required for development and maintenance of the epithelial barrier. It is hypothesized that microRNAs are involved in regulating epithelial anti-microbial defenses by targeting key epithelial effector molecules and/or influencing intracellular signaling pathways. Additionally, aberrant microRNA expression has been implicated in the pathogenesis of various diseases at the skin and mucosa. Increased understanding of the role of microRNAs in epithelial immunoregulation and identification of microRNAs of pathogenetic significance will enhance our understanding of epithelial immunobiology and immunopathology. PMID:19811319

  13. ERBB2 in Cat Mammary Neoplasias Disclosed a Positive Correlation between RNA and Protein Low Expression Levels: A Model for erbB-2 Negative Human Breast Cancer

    PubMed Central

    Abreu, Rui M. V.; Bastos, Estela; Amorim, Irina; Gut, Ivo G.; Gärtner, Fátima; Chaves, Raquel

    2013-01-01

    Human ERBB2 is a proto-oncogene that codes for the erbB-2 epithelial growth factor receptor. In human breast cancer (HBC), erbB-2 protein overexpression has been repeatedly correlated with poor prognosis. In more recent works, underexpression of this gene has been described in HBC. Moreover, it is also recognised that oncogenes that are commonly amplified or deleted encompass point mutations, and some of these are associated with HBC. In cat mammary lesions (CMLs), the overexpression of ERBB2 (27%–59.6%) has also been described, mostly at the protein level and although cat mammary neoplasias are considered to be a natural model of HBC, molecular information is still scarce. In the present work, a cat ERBB2 fragment, comprising exons 10 to 15 (ERBB2_10–15) was achieved for the first time. Allelic variants and genomic haplotype analyses were also performed, and differences between normal and CML populations were observed. Three amino acid changes, corresponding to 3 non-synonymous genomic sequence variants that were only detected in CMLs, were proposed to damage the 3D structure of the protein. We analysed the cat ERBB2 gene at the DNA (copy number determination), mRNA (expression levels assessment) and protein levels (in extra- and intra protein domains) in CML samples and correlated the last two evaluations with clinicopathological features. We found a positive correlation between the expression levels of the ERBB2 RNA and erbB-2 protein, corresponding to the intracellular region. Additionally, we detected a positive correlation between higher mRNA expression and better clinical outcome. Our results suggest that the ERBB2 gene is post-transcriptionally regulated and that proteins with truncations and single point mutations are present in cat mammary neoplastic lesions. We would like to emphasise that the recurrent occurrence of low erbB-2 expression levels in cat mammary tumours, suggests the cat mammary neoplasias as a valuable model for erbB-2 negative HBC

  14. Progress Towards Drosophila Epithelial Cell Culture

    PubMed Central

    Simcox, Amanda

    2015-01-01

    Drosophila epithelial research is at the forefront of the field; however, there are no well-characterized epithelial cell lines that could provide a complementary in vitro model for studies conducted in vivo. Here, a protocol is described that produces epithelial cell lines. The method uses genetic manipulation of oncogenes or tumor suppressors to induce embryonic primary culture cells to rapidly progress to permanent cell lines. It is, however, a general method and the type of cells that comprise a given line is not controlled experimentally. Indeed, only a small fraction of the lines produced are epithelial in character. For this reason, additional work needs to be done to develop a more robust epithelial cell-specific protocol. It is expected that Drosophila epithelial cell lines will have great utility for in vitro analysis of epithelial biology, particularly high-throughput analyses such as RNAi screens. PMID:23097097

  15. Biomarkers of human colonic cell growth are influenced differently by a history of colonic neoplasia and the consumption of acarbose.

    PubMed

    Weaver, G A; Tangel, C T; Krause, J A; Parfitt, M M; Stragand, J J; Jenkins, P L; Erb, T A; Davidson, R H; Alpern, H D; Guiney, W B; Higgins, P J

    2000-11-01

    The nutritional effects of butyrate on the colonic mucosa and studies of transformed cells suggest that butyrate has anti-colon cancer effects. If butyrate has antineoplastic effects, mucosal growth contrasts between normal subjects and those with a history of colonic neoplasia would parallel changes in growth characteristics caused by butyrate in a colon neoplasia population. To test this hypothesis, rectal biopsies from a survey of colonoscopy patients (n = 50) with and without a history of colonic neoplasia (controls) were compared. Similarly, rectal biopsies were compared from subjects (n = 44) with a colon neoplasia history in an acarbose-placebo crossover trial. Control subjects in the colonoscopy survey had higher bromodeoxyuridine (BrdU) uptake than subjects with a history of neoplasia (P = 0.05). The control subjects also had a higher correlation of BrdU and Ki-67 labeling (P = 0.003). Both findings were paralleled by acarbose use. Acarbose augmented BrdU uptake (P = 0.0001) and improved the correlation of BrdU and Ki-67 labeling (P = 0.013). Acarbose also augmented fecal butyrate (P = 0.0001), which was positively correlated with Ki-67 labeling (P = 0.003). p52 antigen had an earlier pattern of crypt distribution in subjects with a history of colon neoplasia but was not affected by acarbose use. Lewis-Y antigen was expressed earlier in the crypt with acarbose but had similar expression in the colonoscopy survey groups. The use of acarbose to enhance fecal butyrate concentration produced mucosal changes paralleling the findings in control subjects as opposed to those with neoplasia, supporting the concept of an antineoplastic role for butyrate.

  16. Enhancement of early cervical cancer diagnosis with epithelial layer analysis of fluorescence lifetime images.

    PubMed

    Gu, Jun; Fu, Chit Yaw; Ng, Beng Koon; Liu, Lin Bo; Lim-Tan, Soo Kim; Lee, Caroline Guat Lay

    2015-01-01

    This work reports the use of layer analysis to aid the fluorescence lifetime diagnosis of cervical intraepithelial neoplasia (CIN) from H&E stained cervical tissue sections. The mean and standard deviation of lifetimes in single region of interest (ROI) of cervical epithelium were previously shown to correlate to the gold standard histopathological classification of early cervical cancer. These previously defined single ROIs were evenly divided into layers for analysis. A 10-layer model revealed a steady increase in fluorescence lifetime from the inner to the outer epithelial layers of healthy tissue sections, suggesting a close association with cellular maturity. The shorter lifetime and minimal lifetime increase towards the epithelial surface of CIN-affected regions are in good agreement with the absence of cellular maturation in CIN. Mean layer lifetimes in the top-half cervical epithelium were used as feature vectors for extreme learning machine (ELM) classifier discriminations. It was found that the proposed layer analysis technique greatly improves the sensitivity and specificity to 94.6% and 84.3%, respectively, which can better supplement the traditional gold standard cervical histopathological examinations. PMID:25966026

  17. Active p21-activated kinase 1 rescues MCF10A breast epithelial cells from undergoing anoikis.

    PubMed

    Menard, Raymond E; Jovanovski, Andrew P; Mattingly, Raymond R

    2005-07-01

    The protein kinase, PAK1, is overexpressed in human breast cancer and may contribute to malignancy through induction of proliferation and invasiveness. In this study, we examined the role of PAK1 in the survival of detached MCF10A breast epithelial cells to test whether it may also regulate the early stages of neoplasia. MCF10A cells undergo anoikis, as measured by the cleavage of caspase 3 and poly(ADP-ribose) polymerase (PARP), after more than 8 hours of detachment. Endogenous Akt, PAK1, and BAD are phosphorylated in attached MCF10A cells, but these phosphorylation events are all lost during the first 8 hours of detachment. Expression of constitutively active PAK1 or Akt suppresses the cleavage of caspase 3 and PARP in detached MCF10A cells. Co-overexpression of active PAK1 with dominant-negative Akt, or of active Akt with dominant-negative PAK1, still suppresses anoikis. Thus, Akt and PAK1 enhance survival through pathways that are at least partially independent. PAK1-dependent regulation of anoikis is likely to occur early in the apoptotic cascade as expression of dominant-negative PAK1 increased the cleavage of the upstream caspase 9, while constitutively active PAK1 inhibited caspase 9 activation. These results support a role for activated PAK1 in the suppression of anoikis in MCF10A epithelial cells.

  18. Vertex Models of Epithelial Morphogenesis

    PubMed Central

    Fletcher, Alexander G.; Osterfield, Miriam; Baker, Ruth E.; Shvartsman, Stanislav Y.

    2014-01-01

    The dynamic behavior of epithelial cell sheets plays a central role during numerous developmental processes. Genetic and imaging studies of epithelial morphogenesis in a wide range of organisms have led to increasingly detailed mechanisms of cell sheet dynamics. Computational models offer a useful means by which to investigate and test these mechanisms, and have played a key role in the study of cell-cell interactions. A variety of modeling approaches can be used to simulate the balance of forces within an epithelial sheet. Vertex models are a class of such models that consider cells as individual objects, approximated by two-dimensional polygons representing cellular interfaces, in which each vertex moves in response to forces due to growth, interfacial tension, and pressure within each cell. Vertex models are used to study cellular processes within epithelia, including cell motility, adhesion, mitosis, and delamination. This review summarizes how vertex models have been used to provide insight into developmental processes and highlights current challenges in this area, including progressing these models from two to three dimensions and developing new tools for model validation. PMID:24896108

  19. Modular video endoscopy for in vivo cross-polarized and vital-dye fluorescence imaging of Barrett's-associated neoplasia

    NASA Astrophysics Data System (ADS)

    Thekkek, Nadhi; Pierce, Mark C.; Lee, Michelle H.; Polydorides, Alexandros D.; Flores, Raja M.; Anandasabapathy, Sharmila; Richards-Kortum, Rebecca R.

    2013-02-01

    A modular video endoscope is developed and tested to allow imaging in different modalities. This system incorporates white light imaging (WLI), cross-polarized imaging (CPI), and vital-dye fluorescence imaging (VFI), using interchangeable filter modules. CPI and VFI are novel endoscopic modalities that probe mucosal features associated with Barrett's neoplasia. CPI enhances vasculature, while VFI enhances glandular architecture. In this pilot study, we demonstrate the integration of these modalities by imaging areas of Barrett's metaplasia and neoplasia in an esophagectomy specimen. We verify that those key image features are also observed during an in vivo surveillance procedure. CPI images demonstrate improved visualization of branching blood vessels associated with neoplasia. VFI images show glandular architecture with increased glandular effacement associated with neoplasia. Results suggests that important pathologic features seen in CPI and VFI are not visible during standard endoscopic white light imaging, and thus the modalities may be useful in future in vivo studies for discriminating neoplasia from Barrett's metaplasia. We further demonstrate that the integrated WLI/CPI/VFI endoscope is compatible with complementary high-resolution endomicroscopy techniques such as the high-resolution microendoscope, potentially enabling two-step ("red-flag" widefield plus confirmatory high-resolution imaging) protocols to be enhanced.

  20. PDX-1 is a therapeutic target for pancreatic cancer, insulinoma and islet neoplasia using a novel RNA interference platform.

    PubMed

    Liu, Shi-He; Rao, Donald D; Nemunaitis, John; Senzer, Neil; Zhou, Guisheng; Dawson, David; Gingras, Marie-Claude; Wang, Zhaohui; Gibbs, Richard; Norman, Michael; Templeton, Nancy S; Demayo, Francesco J; O'Malley, Bert; Sanchez, Robbi; Fisher, William E; Brunicardi, F Charles

    2012-01-01

    Pancreatic and duodenal homeobox-1 (PDX-1) is a transcription factor that regulates insulin expression and islet maintenance in the adult pancreas. Our recent studies demonstrate that PDX-1 is an oncogene for pancreatic cancer and is overexpressed in pancreatic cancer. The purpose of this study was to demonstrate that PDX-1 is a therapeutic target for both hormonal symptoms and tumor volume in mouse models of pancreatic cancer, insulinoma and islet neoplasia. Immunohistochemistry of human pancreatic and islet neoplasia specimens revealed marked PDX-1 overexpression, suggesting PDX-1 as a "drugable" target within these diseases. To do so, a novel RNA interference effector platform, bifunctional shRNA(PDX-1), was developed and studied in mouse and human cell lines as well as in mouse models of pancreatic cancer, insulinoma and islet neoplasia. Systemic delivery of bi-shRNA(humanPDX-1) lipoplexes resulted in marked reduction of tumor volume and improved survival in a human pancreatic cancer xenograft mouse model. bi-shRNA(mousePDX-1) lipoplexes prevented death from hyperinsulinemia and hypoglycemia in an insulinoma mouse model. shRNA(mousePDX-1) lipoplexes reversed hyperinsulinemia and hypoglycemia in an immune-competent mouse model of islet neoplasia. PDX-1 was overexpressed in pancreatic neuroendocrine tumors and nesidioblastosis. These data demonstrate that PDX-1 RNAi therapy controls hormonal symptoms and tumor volume in mouse models of pancreatic cancer, insulinoma and islet neoplasia, therefore, PDX-1 is a potential therapeutic target for these pancreatic diseases.

  1. A profile of cases of gestational trophoblastic neoplasia at a large tertiary centre in dubai.

    PubMed

    Rangwala, Tasneem H; Badawi, Faiza

    2011-01-01

    Objectives. To study (1) the prevalence of different types of gestational trophoblastic neoplasia (GTN) in the local and nonlocal population of women at Al Wasl Hospital, a tertiary level referral centre for northern Emirates, (2) the safety of cervical preparation before uterine evacuation, (3) the role of repeat uterine evacuation in curing these cases, and (4) the percentage of cases ultimately requiring chemotherapy. Material and Methods. Retrospective analysis of case records of 35 women with diagnosis of gestational trophoblastic neoplasia were managed in the Department of Obstetrics and Gynecology at Al Wasl Hospital, over a 2-year period between January 2007 to December 2008. Results. 35 cases of gestational trophoblastic neoplasia were seen in a 2-year period (January 2007 to December 2008) at Al Wasl Hospital, with 7000 deliveries per year, prevalence being 1 in 400 live births. 60% cases were local Arabs. Histopathology revealed complete mole in 13 cases, partial mole in 17 cases, hydropic degeneration of villi in 4 cases, and no identifiable tissue in 1 case. No cases of choriocarcinoma or placental site trophoblastic tumour were seen during the study period. 34% cases received cervical preparation with prostaglandins prior to surgical curettage. Complications were minor. 62% were cured by primary suction curettage, 12% after second (repeat) uterine evacuation, and 25% needed single drug chemotherapy. 8% cases defaulted after primary evacuation and were lost to followup. Conclusions. Prevalence of GTN in the local Arab population is similar to other Asian populations. The majority of cases are cured by simple suction uterine curettage. Cervical preparation with prostaglandins should be done in selected cases to avoid perforation during evacuation. Second (repeat) uterine evacuation can be curative in some cases with strict selection criteria and avoid the need for chemotherapy. Regional registry of cases is needed to estimate the true incidence of this

  2. Minichromosome maintenance complex component 7 has an important role in the invasion of papillary urothelial neoplasia

    PubMed Central

    GUAN, BINGXIN; WANG, XIAOYING; YANG, JINGYAN; ZHOU, CHENGJUN; MENG, YAN

    2015-01-01

    The aims of the present study were to investigate the expression of minichromosome maintenance complex component 7 (MCM7) and determine its association with tumor proliferation and invasion in pathological tumor (pT)a and pT1 papillary urothelial neoplasia. The MCM7, MCM3 and Ki67 proteins were detected in 154 cases of urothelial neoplasia using immunohistochemical analysis. The expression of MCM7 significantly increased (P<0.001) as the pathological stage and grade progressed between inverted papilloma, papillary urothelial neoplasm of low malignant potential (PUNLMP), pTa tumor and pT1 tumor. However, no statistically significant difference in MCM7 staining was observed between low-grade pTa tumors and PUNLMP (P=0.2294). In contrast to MCM7, MCM3 was highly expressed in all stages of urothelial neoplasia, with no statistically significant differences observed between the tumor types (P=0.2993, 0.3885 and 0.8489 for pTa tumors, PUNLMP and inverted papiloma, respectively). Furthermore, MCM7 expression was elevated with increased tumor grade and was positively correlated with Ki67 expression (rs=0.9106, P<0.001). However, MCM3 expression was not correlated with MCM7 or Ki67 expression (rs=0.0734, P=0.3657 and rs=0.0638, P=0.4318, respectively). In conclusion, MCM7 overexpression may simultaneously promote tumor proliferation and invasion. Furthermore, it may be a reliable marker for the pathological differential diagnosis of pTa and pT1 papillary urothelial neoplasms; therefore, MCM7 expression may be used to predict tumor prognosis and behavior. PMID:26622601

  3. Fatal Cases of Gestational Trophoblastic Neoplasia in a National Trophoblastic Disease Reference Center in Dakar Senegal

    PubMed Central

    Gueye, Mamour; Ndiaye-Gueye, Mame Diarra; Kane Gueye, Serigne Modou; Moreau, Jean Charles

    2016-01-01

    Objectives: The objectives of this study were to analyze deaths after gestational trophoblastic neoplasia and to determine the factors of treatment failure. Methods: This is a retrospective study in Aristide Le Dantec teaching Hospital in Dakar, Senegal, between 1 January 2006 and 31 December 2014. We took into account socio-epidemiological characteristics of patients, initial diagnosis, time between uterine evacuation and admission, time to onset of gestational trophoblastic neoplasia (GTN), treatment received (deadlines, protocols), difficulties experienced in the diagnosis and the initiation of treatment and survival. Results: In total, 1044 patients were admitted during the study period; 164 cases of GTN were diagnosed (15.7%); and 21 deaths occurred leading to a specific lethality of 12.8%. The average age was 30 years. Almost all patients (n = 18; 85.7%) had low income or no income. Eight out of 21 patients (38.1%) were seen in our department after GTN onset. The mean time to onset of GTN of all patients was 22.1 weeks. For 66.6%, histology was not available; the diagnosis of hydatidiform mole was made on the clinical history and sonographic features and GTN on human chorionic gonadotrophin (hCG) evolution and ultrasound findings. None of the patients had regular chemotherapy due to financial reasons. Patients who died within 3 months after diagnosis had metastatic tumors (7 of 21). All these women had resistance to treatment or progressed after three courses of chemotherapy. Ten of the 12 women with high-risk GTN were not treated with multi-agent chemotherapy (EMA-CO) for purely financial reasons. Conclusion and Global Health Implications: The high incidence and mortality require a profound reorganization of our health system and a high awareness of practitioners to refer to time or to declare all suspected cases of hydatidiform mole or gestational trophoblastic neoplasia.

  4. Fatal Cases of Gestational Trophoblastic Neoplasia in a National Trophoblastic Disease Reference Center in Dakar Senegal

    PubMed Central

    Gueye, Mamour; Ndiaye-Gueye, Mame Diarra; Kane Gueye, Serigne Modou; Moreau, Jean Charles

    2016-01-01

    Objectives: The objectives of this study were to analyze deaths after gestational trophoblastic neoplasia and to determine the factors of treatment failure. Methods: This is a retrospective study in Aristide Le Dantec teaching Hospital in Dakar, Senegal, between 1 January 2006 and 31 December 2014. We took into account socio-epidemiological characteristics of patients, initial diagnosis, time between uterine evacuation and admission, time to onset of gestational trophoblastic neoplasia (GTN), treatment received (deadlines, protocols), difficulties experienced in the diagnosis and the initiation of treatment and survival. Results: In total, 1044 patients were admitted during the study period; 164 cases of GTN were diagnosed (15.7%); and 21 deaths occurred leading to a specific lethality of 12.8%. The average age was 30 years. Almost all patients (n = 18; 85.7%) had low income or no income. Eight out of 21 patients (38.1%) were seen in our department after GTN onset. The mean time to onset of GTN of all patients was 22.1 weeks. For 66.6%, histology was not available; the diagnosis of hydatidiform mole was made on the clinical history and sonographic features and GTN on human chorionic gonadotrophin (hCG) evolution and ultrasound findings. None of the patients had regular chemotherapy due to financial reasons. Patients who died within 3 months after diagnosis had metastatic tumors (7 of 21). All these women had resistance to treatment or progressed after three courses of chemotherapy. Ten of the 12 women with high-risk GTN were not treated with multi-agent chemotherapy (EMA-CO) for purely financial reasons. Conclusion and Global Health Implications: The high incidence and mortality require a profound reorganization of our health system and a high awareness of practitioners to refer to time or to declare all suspected cases of hydatidiform mole or gestational trophoblastic neoplasia. PMID:27622010

  5. Early identification of cervical neoplasia with Raman spectroscopy and advanced methods for biomedical applications

    NASA Astrophysics Data System (ADS)

    Jess, Phillip R. T.; Smith, Daniel D. W.; Mazilu, Michael; Cormack, Iain; Riches, Andrew C.; Herrington, C. Simon; Dholakia, Kishan

    2008-02-01

    Early detection of malignant tumours, or their precursor lesions, can dramatically improve patient outcome. High risk human Papillomavirus (HPV), particularly HPV16, infection can lead to the initiation and development of uterine cervical neoplasia. Bearing this in mind the identification of the effects of HPV infection may have clinical value. In this manuscript we investigate the application of Raman microspectroscopy to detect the presence of HPV in cultured cells when compared with normal cells. We also investigate the effect of sample fixation, which is a common clinical practice, on the ability of Raman spectroscopy to detect the presence of HPV. Raman spectra were acquired from Primary Human Keratinocytes (PHK), PHK expressing the E7 gene of HPV 16 (PHK E7) and CaSki cells, an HPV16 containing cervical carcinoma derived cell line. The average Raman spectra display variations, mostly in peaks relating to DNA and proteins, consistent with HPV gene expression and the onset of neoplasia in both live and fixed samples. Principle component analysis was used to objectively discriminate between the cells types giving sensitivities up to 100% for the comparison between PHK and CaSki. These results show that Raman spectroscopy can discriminate between cell lines representing different stages of cervical neoplasia. Furthermore Raman spectroscopy was able to identify cells expressing the HPV 16 E7 gene suggesting the approach may be of value in clinical practice. Finally this technique was also able to detect the effects of the virus in fixed samples demonstrating the compatibility of this technique with current cervical screening methods. However if Raman spectroscopy is to make a significant impact in clinical practice the long acquisition times must be addressed. In this report we examine the potential for beam shaping and advanced to improve the signal to noise ration hence subsequently facilitating a reduction in acquisition time.

  6. [Medullary thyroid carcinoma in a 10-month-old child with multiple endocrine neoplasia 2B].

    PubMed

    Mathiesen, Jes Sloth; Døssing, Helle; Bender, Lars; Godballe, Christian

    2014-01-27

    In infants at risk of multiple endocrine neoplasia type 2B (MEN2B) the American Thyroid Association recommends genetic testing as soon as possible after birth and that thyroidectomy should be performed in MEN2B RET-mutation positive individuals as soon as possible and if possible within the first year of life. We present a ten-month-old girl with MEN2B who had prophylactic thyroidectomy. The surgical specimen showed medullary thyroid carcinoma. This case emphasizes the need for early diagnosis and prophylactic thyroidectomy in MEN2B patients. PMID:27498810

  7. Prospective evaluation of a portable depth-sensitive optical spectroscopy device to identify oral neoplasia

    PubMed Central

    Schwarz, Richard A.; Gao, Wen; Stepanek, Vanda M. T.; Le, Tao T.; Bhattar, Vijayashree S.; Williams, Michelle D.; Wu, Jessica K.; Vigneswaran, Nadarajah; Adler-Storthz, Karen; Gillenwater, Ann M.; Richards-Kortum, Rebecca

    2011-01-01

    A portable, depth-sensitive clinical spectroscopy device for noninvasive early diagnosis of oral cancer is described. We carried out a pilot study to evaluate the ability of the device to identify oral neoplasia using a previously developed diagnostic algorithm. A total of 79 oral sites in 33 subjects, including 28 patients with oral lesions and 5 healthy volunteers, were measured and analyzed. Measurements of 54 nonkeratinized oral sites yielded an area under the receiver operating characteristic curve of 0.90. Measurements of 25 keratinized oral sites yielded an area under the receiver operating characteristic curve of 0.83. PMID:21326639

  8. Multiple Endocrine Neoplasia: A Genetically Diverse Group of Familial Tumor Syndromes.

    PubMed

    Pacheco, M Cristina

    2016-06-01

    Multiple endocrine neoplasia (MEN) syndrome is a familial cancer syndrome characterized by neuroendocrine tumors. The syndrome encompasses four major subtypes: MEN1, MEN2A, MEN2B, and MEN4. MEN1 is caused by mutations in the MEN1 gene, MEN2A and MEN2B are caused by mutations in RET, and MEN4 is caused by mutations in CDKNB1. All are inherited in an autosomal dominant pattern, but de novo cases do arise. While all subtypes are associated with neuroendocrine tumors, each has characteristic organ involvement. Identifying patients with the syndrome can aid in proper screening and treatment. PMID:27617149

  9. c-Myc Oncoprotein: A Dual Pathogenic Role in Neoplasia and Cardiovascular Diseases?

    PubMed Central

    Napoli, Claudio; Lerman, Lilach O; de Nigris, Filomena; Sica, Vincenzo

    2002-01-01

    Abstract A growing body of evidence indicates that c-Myc can play a pivotal role both in neoplasia and cardiovascular diseases. Indeed, alterations of the basal machinery of the cell and perturbations of c-Myc-dependent signaling network are involved in the pathogenesis of certain cardiovascular disorders. Down-regulation of c-Myc induced by intervention with antioxidants or by antisense technology may protect the integrity of the arterial wall as well as neoplastic tissues. Further intervention studies are necessary to investigate the effects of tissue-specific block of c-Myc overexpression in the development of cardiovascular diseases. PMID:11988837

  10. Anal intraepithelial neoplasia among HIV-positive men who have sex with men.

    PubMed

    Mata-Marín, José A; Hernández-Figueroa, Jorge; Huerta-García, Gloria; Sandoval-Ramírez, Jorge; Pichardo-Farfán, Miguel; Manjarrez-Tellez, Bulmaro; Ramírez-Mendoza, Pablo; Gaytan-Martínez, Jesús

    2015-11-01

    Neoplasia is the second most common cause of mortality in HIV patients. The prevalence of anal cancer among men who have sex with men (MSM) has continued to increase since the introduction of antiretroviral therapy. We screened 94 HIV-infected MSM patients. We found high-grade squamous intraepithelial lesions (HSIL) in six of the patients. The calculated prevalence of HSIL was 6.4% (95% confidence interval: 2.9-13.2). The study and implementation of screening programs for high-risk groups is a priority.

  11. Screening for pancreatic neoplasia in high-risk individuals: who, what, when, how?

    PubMed

    Canto, Marcia Irene

    2005-07-01

    Pancreatic cancer (PC) is a highly lethal disease. Most symptomatic, clinically detected PCs are advanced and not curable. Indeed, the estimated 5-year survival rate is 4%, which is attributable to late diagnosis and low resection rate. Screening of high-risk individuals and early detection of small PCs and precursor lesions might improve the outcome if curative therapy could be offered in the presymptomatic stage. This article summarizes the available published data and preliminary results and discusses the different approaches to screening for pancreatic neoplasia at 2 university-based programs in the United States.

  12. Epithelial cells and Von Gierke's disease.

    PubMed

    Negishi, H; Benke, P J

    1977-08-01

    Epithelial cells and not fibroblasts from human liver and amniotic fluid contain inducible glucose-6-phosphatase (G-6-Pase) activity. The diagnosis of Von Gierke's disease has been made in a patient with hepatomegaly utilizing cultured epithelial cells grown from a liver biopsy. G-6-Pase activity in epithelial cells from this patient could not be induced by dibutyryl cyclic AMP and theophylline. This is the first use of epithelial cells for diagnosis of a metabolic disease. G-6-Pase activity in cloned epithelial cells from amniotic fluid increases 2- to 3-fold after 24-hr exposure to dibutyryl cyclic AMP and theophylline. The prenatal diagnosis of Von Gierke's disease may be possible in a laboratory experienced with these techniques if epithelial cell growth is obtained from amniotic fluid. PMID:196249

  13. Secretory component: a glandular epithelial cell marker.

    PubMed Central

    Harris, J. P.; South, M. A.

    1981-01-01

    Secretory component (SC) has been demonstrated to be produced by both normal and malignantly transformed glandular epithelial cells. By an indirect immunofluorescent technique, this study surveys tumors of varied cellular origin in order to determine the reliability of SC as a marker for tumor cells derived from glandular epithelium. Both primary and metastatic tumors of glandular epithelial origin demonstrated SC fluorescence, while nonglandular epithelial tumors did not. This observation was extended to live single-cell preparations, which demonstrated intense cell-surface fluorescence only when glandular epithelial tumors cells were examined. Additionally, fixed, cytocentrifuged, single-cell preparations of glandular epithelial tumors demonstrated cytoplasmic SC fluorescence. When breast carcinoma was examined, all cases demonstrated SC, regardless of the degree of differentiation. This assay appears to have useful clinical application in that the finding of SC provides indication of the glandular epithelial origin of a malignantly transformed cell. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:6271014

  14. Influence of disseminated neoplasia, trematode infections and gametogenesis on surfacing and mortality in the cockle Cerastoderma edule.

    PubMed

    Morgan, E; O'Riordan, R M; Kelly, T C; Culloty, S C

    2012-02-17

    Cerastoderma edule is a widely distributed bivalve mollusc, commercially exploited throughout Europe and is also an important food source for birds and crustaceans. Recently, mass surfacing and mortalities of cockles have been observed and reported at sites in Ireland and elsewhere, particularly in the summer months. One such site is Flaxfort Strand, Courtmacsherry Bay, County Cork, Ireland, an important feeding area used by many seabirds during the summer months. For the past few years large numbers of surfaced cockles have been observed at the site in a moribund condition. Samples of cockles from this area were collected over the summer months and their health status assessed. Cockles that had surfaced (moribund) and those still buried in the sediment were quantified and screened: sex, gonadal maturity and size class of cockles were also determined. Disseminated neoplasia and trematodes were observed in screened cockles. The most significant finding during the study was that mortalities and surfacing of cockles was related to a greater incidence of disseminated neoplasia. No neoplasia was observed in the smallest and largest size classes. There was a significantly higher prevalence of neoplasia in moribund cockles than in buried cockles, whereas in both groups a similar concentration of trematode metacercariae was observed in the screened tissues. Also, most of the cockles that had surfaced were either in the process of spawning or were spent. Overall a much larger percentage of moribund cockles exhibited both trematode infections plus neoplasia compared with buried cockles. A combination of the presence of neoplasia and trematodes, along with stress related to spawning, may immunocompromise the cockless, causing the animals to surface and become moribund.

  15. Dextran sulfate sodium-induced colitis-associated neoplasia: a promising model for the development of chemopreventive interventions.

    PubMed

    Clapper, Margie Lee; Cooper, Harry Stanley; Chang, Wen-Chi Lee

    2007-09-01

    Individuals diagnosed with ulcerative colitis face a significantly increased risk of developing colorectal dysplasia and cancer during their lifetime. To date, little attention has been given to the development of a chemopreventive intervention for this high-risk population. The mouse model of dextran sulfate sodium (DSS) - induced colitis represents an excellent preclinical system in which to both characterize the molecular events required for tumor formation in the presence of inflammation and assess the ability of select agents to inhibit this process. Cyclic administration of DSS in drinking water results in the establishment of chronic colitis and the development of colorectal dysplasias and cancers with pathological features that resemble those of human colitis-associated neoplasia. The incidence and multiplicity of lesions observed varies depending on the mouse strain used (ie, Swiss Webster, C57BL/6J, CBA, ICR) and the dose (0.7%-5.0%) and schedule (1-15 cycles with or without a subsequent recovery period) of DSS. The incidence of neoplasia can be increased and its progression to invasive cancer accelerated significantly by administering DSS in combination with a known colon carcinogen (azoxymethane (AOM), 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-1- methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)) or iron. More recent induction of colitis-associated neoplasia in genetically defined mouse strains has provided new insight into the role of specific genes (ie, adenomatous polyposis coli (Apc), p53, inducible nitric oxide synthase (iNOS), Msh2) in the development of colitis-associated neoplasias. Emerging data from chemopreventive intervention studies document the efficacy of several agents in inhibiting DSS-induced neoplasia and provide great promise that colitis-associated colorectal neoplasia is a preventable disease.

  16. Implementation of a program to improve the quality of colonoscopy increases the neoplasia detection rate: a prospective study

    PubMed Central

    Viola, Luis Alberto; Cassella, Federico; Wonaga, Andrés; Arnao Dellamea, Gloria; Di Paola, Leandro; Ubeira Salim, Rodrigo; Fernández, José Luis

    2016-01-01

    Background and study aims: Endoscopists worldwide have been encouraged to report quality indicators in order to evaluate their performance. We aimed to determine whether a program to improve the quality of colonoscopy results in better rates of neoplasia detection. Patients and methods: This is a prospective study set in a private endoscopy center. From May 2009 to March 2010, we evaluated 1573 consecutive colonoscopies (group 1). After the implementation of a quality program, from February 2011 to January 2012, we prospectively evaluated 1583 colonoscopies (group 2). Our quality-enhancing intervention consisted of instructing both patients and endoscopists. We measured the cecal intubation rate and the neoplasia detection rate. Overall neoplasias, high-risk adenomas, carcinomas, right colon adenomas, and adenomas detected in screening studies were analyzed. Results: Cecal intubation was documented in 1384 cases from group 1 (88 %) and 1534 from group 2 (96.9 %) (P < 0.0001). The neoplasia detection rates in groups 1 and 2 were, respectively: neoplasias 288 (18.3 %) and 427 (27 %) (P < 0.0001), high-risk adenomas 76 (4.8 %) and 142 (9 %) (P < 0.0001), carcinomas 16 (1 %) and 21 (1.3 %) (P = 0.52), right colon adenomas 112 (7.1 %) and 154 (9.7 %) (P = 0.01), and adenomas 141 (16.5 %) and 233 (28 %) (P < 0.0001). Conclusions: Implementation of a quality program improves the neoplasia detection rate. Because of the small number of cancerous lesions found in both groups, we were unable to identify differences in the carcinoma detection rate. PMID:26793787

  17. Association of the Genetic Polymorphisms RRM1 -756T>C and -269C>A With Cervical Neoplasia.

    PubMed

    Chang, Ching-Wen; Yang, Shun-Fa; Wang, Po-Hui; Chang, Hsiu-Ju; Liu, Wen-Chi; Tsai, Hsiu-Ting

    2016-10-01

    Cervical neoplasia is one of the most prevalent malignant neoplasms worldwide. Ribonucleotide reductase 1 (RRM1) is thought to play an essential role in modulating the development and progression of cervical neoplasia. Two novel genetic polymorphisms, RRM1 -756T>C and -269 C>A, are significantly correlated with RRM1 expression. Some epidemiological studies have demonstrated that genetic variants play a crucial role in susceptibility to cervical cancer. The present study aimed to identify the genetic polymorphisms RRM1 -756T>C and -269 C>A in patients with cervical neoplasia and healthy controls. In total, 493 subjects, comprising 324 healthy controls and 169 patients with cervical neoplasia, were enrolled for this study. The allelic discrimination of the RRM1 -756T>C (rs11030918) and -269C>A (rs12806698) polymorphisms was assessed using the ABI StepOne™ real-time polymerase chain reaction system and analyzed using Software Design Specification (SDS), Version 3.0, software with TaqMan assays. The risk of cervical cancer was examined, revealing adjusted odds ratios and 95% confidence intervals of 1.25 [0.51, 3.08] and 1.09 [0.43, 2.78] for individuals with CC alleles of RRM1 -756T>C and for individuals with AA alleles of RRM1 -269C>A genetic polymorphisms, respectively, compared to individuals with wild-type RRM1 genetic polymorphisms. No significant genetic interaction effect was observed in susceptibility to cervical neoplasia, and no association was found between genetic polymorphisms and clinical statuses of invasive cervical cancer. The genetic polymorphisms RRM1 -756T>C and -269C>A may not be a factor for susceptibility to cervical neoplasia.

  18. Diagnosis of Retrobulbar Round Cell Neoplasia in a Macaroni Penguin ( Eudyptes chrysolophus ) Through Use of Computed Tomography.

    PubMed

    Woodhouse, Sarah J; Rose, Michelle; Desjardins, Danielle R; Agnew, Dalen W

    2015-03-01

    A 25-year-old female macaroni penguin (Eudyptes chrysolophus) was diagnosed with exophthalmos secondary to retrobulbar neoplasia through use of computed tomography (CT). Histopathologic examination of the mass supported a diagnosis of malignant round cell neoplasia. Immunohistochemical (IHC) labeling was applied to determine cell origin; the neoplastic cells did not label with T-cell marker CD3 or B-cell marker BLA.36 and could not be further characterized. The scleral ossicles precluded evaluation of the retrobulbar space by ultrasonography; therefore, CT scanning is recommended for examination of intraorbital structures in penguin and other avian species.

  19. Evidence of retroviral etiology for disseminated neoplasia in cockles (Cerastoderma edule).

    PubMed

    Romalde, Jesús L; Luz Vilariño, M; Beaz, Roxana; Rodríguez, José M; Díaz, Seila; Villalba, Antonio; Carballal, María J

    2007-02-01

    Epizootiologic outbreaks of disseminated neoplasia have been reported in association with massive mortalities of various bivalve species. In cockles, Cerastoderma edule, this pathological condition was described in Ireland and France. Since 1997, different populations affected by this pathology have been detected in Galicia (NW Spain). Transmission electron microscopy allowed the visualization of virus-like particles in neoplastic cells, resembling a retrovirus-like agent. To confirm this hypothesis, we used a commercial kit for detection and quantification of reverse transcriptase (RT) activity, based on the use of bromo-deoxyuridine triphosphate (BrdUTP) and a BrdU binding antibody conjugated to alkaline phosphatase. In addition, we developed a product-enhanced RT assay using RNA of hepatitis A virus as a template. These two assays showed positive RT activity in 90.9 and 81.8% of samples, respectively, from cockles displaying disseminated neoplasia as determined by light microscopy. These results strongly support the hypothesis of retroviral etiology for this pathological condition.

  20. Lower motor neuron degeneration and familial predisposition to colonic neoplasia in two adult siblings.

    PubMed

    Shaw, P J; Ince, P G; Slade, J; Burn, J; Cartlidge, N E

    1991-11-01

    A previously unreported association between a familial predisposition to colonic neoplasia and familial adult onset lower motor neuron (LMN) degeneration is reported. Two brothers presented at the ages of 53 and 44 years with multiple colonic adenomata and invasive colonic carcinoma respectively. Subsequently both developed a virtually identical pattern of motor neuron disease of progressive muscular atrophy type. At presentation both had LMN weakness affecting predominantly the upper limb and neck muscles. The disease progressed rapidly to involve the lower limb and bulbar musculature and both brothers died after a 15 month course. Necropsy was performed on one brother and showed pathological changes confined to the LMNs with no evidence of involvement of the pyramidal tracts or motor cortex. The combination of these diseases in two brothers may be of importance in the search for genes responsible for familial motor neuron disorders. It is suggested that a genomic search should be directed initially to the vicinity of known colon neoplasia genes, particularly 5q, 17q and 18q.

  1. Progression of naive intraepithelial neoplasia genome to aggressive squamous cell carcinoma genome of uterine cervix

    PubMed Central

    Kim, Min Sung; Baek, In-Pyo; Lee, Sung Hak; Lee, Ah Won; Hur, Soo Young; Kim, Tae-Min; Lee, Sug Hyung; Chung, Yeun-Jun

    2015-01-01

    Although cervical intraepithelial neoplasia (CIN) is considered a neoplasia, its genomic alterations remain unknown. For this, we performed whole-exome sequencing and copy number profiling of three CINs, a microinvasive carcinoma (MIC) and four cervical squamous cell carcinomas (CSCC). Both total mutation and driver mutation numbers of the CINs were significantly fewer than those of the MIC/CSCCs (P = 0.036 and P = 0.018, respectively). Importantly, PIK3CA was altered in all MIC/CSCCs by either mutation or amplification, but not in CINs. The CINs harbored significantly lower numbers of copy number alterations (CNAs) than the MIC/CSCCs as well (P = 0.036). Pathway analysis predicted that the MIC/CSCCs were enriched with cancer-related signalings such as cell adhesion, mTOR signaling pathway and cell migration that were depleted in the CINs. The mutation-based estimation of evolutionary ages identified that CIN genomes were younger than MIC/CSCC genomes. The data indicate that CIN genomes harbor unfixed mutations in addition to human papilloma virus infection but require additional driver hits such as PIK3CA, TP53, STK11 and MAPK1 mutations for CSCC progression. Taken together, our data may explain the long latency from CIN to CSCC progression and provide useful information for molecular diagnosis of CIN and CSCC. PMID:25738363

  2. Targeted therapy of colorectal neoplasia with rapamycin in peptide-labeled pegylated octadecyl lithocholate micelles

    PubMed Central

    Khondee, Supang; Rabinsky, Emily F.; Owens, Scott R.; Joshi, Bishnu P.; Qiu, Zhen; Duan, Xiyu; Zhao, Lili; Wang, Thomas D.

    2015-01-01

    Many powerful drugs have limited clinical utility because of poor water solubility and high systemic toxicity. Here, we formulated a targeted nanomedicine, rapamycin encapsulated in pegylated octadecyl lithocholate micelles labeled with a new ligand for colorectal neoplasia, LTTHYKL peptide. CPC;Apc mice that spontaneously develop colonic adenomas were treated with free rapamycin, plain rapamycin micelles, and peptide-labeled rapamycin micelles via intraperitoneal injection for 35 days. Endoscopy was performed to monitor adenoma regression in vivo. We observed complete adenoma regression at the end of therapy. The mean regression rate for peptide-labeled rapamycin micelles was significantly greater than that for plain rapamycin micelles, P<0.01. On immunohistochemistry, we observed a significant reduction in phospho-S6 but not β-catenin expression and reduced tumor cell proliferation, suggesting greater inhibition of downstream mTOR signaling. We observed significantly reduced renal toxicity for peptide-labeled rapamycin micelles compared to that of free drug, and no other toxicities were found on chemistries. Together, this unique targeted micelle represents a potential therapeutic for colorectal neoplasia with comparable therapeutic efficacy to rapamycin free drug and significantly less systemic toxicity. PMID:25483425

  3. Loss of adipose triglyceride lipase is associated with human cancer and induces mouse pulmonary neoplasia.

    PubMed

    Al-Zoughbi, Wael; Pichler, Martin; Gorkiewicz, Gregor; Guertl-Lackner, Barbara; Haybaeck, Johannes; Jahn, Stephan W; Lackner, Carolin; Liegl-Atzwanger, Bernadette; Popper, Helmut; Schauer, Silvia; Nusshold, Elisa; Kindt, Alida S D; Trajanoski, Zlatko; Speicher, Michael R; Haemmerle, Guenther; Zimmermann, Robert; Zechner, Rudolf; Vesely, Paul W; Hoefler, Gerald

    2016-06-01

    Metabolic reprogramming is a hallmark of cancer. Understanding cancer metabolism is instrumental to devise innovative therapeutic approaches. Anabolic metabolism, including the induction of lipogenic enzymes, is a key feature of proliferating cells. Here, we report a novel tumor suppressive function for adipose triglyceride lipase (ATGL), the rate limiting enzyme in the triglyceride hydrolysis cascade.In immunohistochemical analysis, non-small cell lung cancers, pancreatic adenocarcinoma as well as leiomyosarcoma showed significantly reduced levels of ATGL protein compared to corresponding normal tissues. The ATGL gene was frequently deleted in various forms of cancers. Low levels of ATGL mRNA correlated with significantly reduced survival in patients with ovarian, breast, gastric and non-small cell lung cancers. Remarkably, pulmonary neoplasia including invasive adenocarcinoma developed spontaneously in mice lacking ATGL pointing to an important role for this lipase in controlling tumor development.Loss of ATGL, as detected in several forms of human cancer, induces spontaneous development of pulmonary neoplasia in a mouse model. Our results, therefore, suggest a novel tumor suppressor function for ATGL and contribute to the understanding of cancer metabolism. We propose to evaluate loss of ATGL protein expression for the diagnosis of malignant tumors. Finally, modulation of the lipolytic pathway may represent a novel therapeutic approach in the treatment of human cancer.

  4. Intertumor linkage of age-adjusted incidence rate in 15 human neoplasias of both sexes.

    PubMed

    Kodama, M; Kodama, T; Murakami, M; Yokochi, T

    2000-01-01

    We report here that the application of the least square method of Gauss to the log-transformed age-adjusted incidence rate changes in time and space, as tested with either the male-female or the female-male tumor pairs for each of 15 tumor entities, has revealed the presence of intertumor linkage that was conditioning the changes of two cancer risk parameters to let them fit to the equilibrium model with close resemblance to the chemical equilibrium model. The dissimilarity of the cancer risk equilibrium model to the chemical equilibrium model--topological dissociation between the equilibrium model of centripetal force (r = -1.000) and that of centrifugal force (r = +1.000)--was discussed in the light of the concept of the oncogene activation-tumor suppressor gene inactivation. The proposed network hypothesis of human neoplasia found supporting evidence in the corresponding changes of the statistical features of human neoplasias with and without sex discrimination of cancer risk. PMID:10836207

  5. Risk for gastric neoplasias in patients with chronic atrophic gastritis: A critical reappraisal

    PubMed Central

    Vannella, Lucy; Lahner, Edith; Annibale, Bruno

    2012-01-01

    Chronic atrophic gastritis (CAG) is an inflammatory condition characterized by the loss of gastric glandular structures which are replaced by connective tissue (non-metaplastic atrophy) or by glandular structures inappropriate for location (metaplastic atrophy). Epidemiological data suggest that CAG is associated with two different types of tumors: Intestinal-type gastric cancer (GC) and type I gastric carcinoid (TIGC). The pathophysiological mechanisms which lead to the development of these gastric tumors are different. It is accepted that a multistep process initiating from Helicobacter pylori-related chronic inflammation of the gastric mucosa progresses to CAG, intestinal metaplasia, dysplasia and, finally, leads to the development of GC. The TIGC is a gastrin-dependent tumor and the chronic elevation of gastrin, which is associated with CAG, stimulates the growth of enterochromaffin-like cells with their hyperplasia leading to the development of TIGC. Thus, several events occur in the gastric mucosa before the development of intestinal-type GC and/or TIGC and these take several years. Knowledge of CAG incidence from superficial gastritis, its prevalence in different clinical settings and possible risk factors associated with the progression of this condition to gastric neoplasias are important issues. This editorial intends to provide a brief review of the main studies regarding incidence and prevalence of CAG and risk factors for the development of gastric neoplasias. PMID:22493541

  6. Hyperspectral wide gap second derivative analysis for in vivo detection of cervical intraepithelial neoplasia

    NASA Astrophysics Data System (ADS)

    Zheng, Wenli; Wang, Chaojian; Chang, Shufang; Zhang, Shiwu; Xu, Ronald X.

    2015-12-01

    Hyperspectral reflectance imaging technique has been used for in vivo detection of cervical intraepithelial neoplasia. However, the clinical outcome of this technique is suboptimal owing to multiple limitations such as nonuniform illumination, high-cost and bulky setup, and time-consuming data acquisition and processing. To overcome these limitations, we acquired the hyperspectral data cube in a wavelength ranging from 600 to 800 nm and processed it by a wide gap second derivative analysis method. This method effectively reduced the image artifacts caused by nonuniform illumination and background absorption. Furthermore, with second derivative analysis, only three specific wavelengths (620, 696, and 772 nm) are needed for tissue classification with optimal separability. Clinical feasibility of the proposed image analysis and classification method was tested in a clinical trial where cervical hyperspectral images from three patients were used for classification analysis. Our proposed method successfully classified the cervix tissue into three categories of normal, inflammation and high-grade lesion. These classification results were coincident with those by an experienced gynecology oncologist after applying acetic acid. Our preliminary clinical study has demonstrated the technical feasibility for in vivo and noninvasive detection of cervical neoplasia without acetic acid. Further clinical research is needed in order to establish a large-scale diagnostic database and optimize the tissue classification technique.

  7. Clinical value of tumor doubling estimations in multiple endocrine neoplasia type II.

    PubMed

    Jackson, C E; Talpos, G B; Block, M A; Norum, R A; Lloyd, R V; Tashjian, A H

    1984-12-01

    Experience with children with multiple endocrine neoplasia (MEN) type IIb has emphasized that medullary thyroid cancer (MTC) in MEN IIb is more aggressive than in MEN IIa. Earlier ages of onset and apparently more rapid growth of MTC in MEN IIb suggest that these tumors have earlier ages of conversion to malignant states and/or shorter doubling times. The age at which a hyperplastic C cell becomes a malignant cell and the true doubling time cannot be estimated presently. Maximum volume-doubling times of 35 and 75 days (21 to 26 doublings) were calculated from tumor size and age at operation in five patients with MEN IIb aged 2 to 5 years. Calculations in 20 patients with MEN IIa revealed maximum doubling times of 110 to 440 days, with ages ranging from 7 to 29 years and number of doubling ranging from 18 to 38. Positive provocative calcitonin tests in two adult patients with MEN IIa after 10 to 11 years of repeated negative tests suggest a minimum doubling time of 190 to 210 days. Such experience emphasizes that negative stimulated calcitonin tests less than 11 years after operation do not provide assurance of cures for MTC in MEN IIa although negative tests after more than 5 years for MEN IIb are encouraging. Calculations of volume doublings accounting for various-sized tumors are compatible with Knudson's two-mutational-event theory on the initiation of neoplasia.

  8. Loss of adipose triglyceride lipase is associated with human cancer and induces mouse pulmonary neoplasia

    PubMed Central

    Al-Zoughbi, Wael; Pichler, Martin; Gorkiewicz, Gregor; Guertl-Lackner, Barbara; Haybaeck, Johannes; Jahn, Stephan W.; Lackner, Carolin; Liegl-Atzwanger, Bernadette; Popper, Helmut; Schauer, Silvia; Nusshold, Elisa; Kindt, Alida S. D.; Trajanoski, Zlatko; Speicher, Michael R.; Haemmerle, Guenther; Zimmermann, Robert; Zechner, Rudolf; Vesely, Paul W.; Hoefler, Gerald

    2016-01-01

    Metabolic reprogramming is a hallmark of cancer. Understanding cancer metabolism is instrumental to devise innovative therapeutic approaches. Anabolic metabolism, including the induction of lipogenic enzymes, is a key feature of proliferating cells. Here, we report a novel tumor suppressive function for adipose triglyceride lipase (ATGL), the rate limiting enzyme in the triglyceride hydrolysis cascade. In immunohistochemical analysis, non-small cell lung cancers, pancreatic adenocarcinoma as well as leiomyosarcoma showed significantly reduced levels of ATGL protein compared to corresponding normal tissues. The ATGL gene was frequently deleted in various forms of cancers. Low levels of ATGL mRNA correlated with significantly reduced survival in patients with ovarian, breast, gastric and non-small cell lung cancers. Remarkably, pulmonary neoplasia including invasive adenocarcinoma developed spontaneously in mice lacking ATGL pointing to an important role for this lipase in controlling tumor development. Loss of ATGL, as detected in several forms of human cancer, induces spontaneous development of pulmonary neoplasia in a mouse model. Our results, therefore, suggest a novel tumor suppressor function for ATGL and contribute to the understanding of cancer metabolism. We propose to evaluate loss of ATGL protein expression for the diagnosis of malignant tumors. Finally, modulation of the lipolytic pathway may represent a novel therapeutic approach in the treatment of human cancer. PMID:27213586

  9. Survey of neoplasia in red kangaroos (Macropus rufus), 1992-2002, in a zoological collection.

    PubMed

    Suedmeyer, Wm Kirk; Johnson, Gayle

    2007-06-01

    An increase in the proportion of cases with neoplasia observed in a collection of captive red kangaroos (Macropus rufus) when compared with historical records and the paucity of reported neoplasms in kangaroos in the literature prompted a 10-yr review of all red kangaroo necropsies. Individual necropsy, medical, and inventory records for all kangaroos at the Kansas City Zoo were reviewed for the period 1 January 1992 to 31 December 2002. Two squamous cell carcinomas of the oral cavity, two mammary gland adenocarcinomas, a multicentric T-cell lymphosarcoma, and one submucosal pyloric lipoma were diagnosed in six of 28 kangaroo deaths. Three neoplasms were diagnosed antemortem. Four of the six neoplasms were considered malignant, and all four had metastasized. The mean age at death was 11 yr. All six animals with neoplasms were female; however, the exhibit population was composed solely of females. Only 11 cases of neoplasia in red kangaroos have been reported in the literature. On the basis of these cases and a review of the literature, the most commonly observed neoplasms in red kangaroos are mammary gland adenocarcinomas and oral squamous cell carcinomas. Common denominators were not identified in these cases, although chronic gingivitis could have been a contributing factor in the development of the oral squamous cell carcinomas.

  10. Assessment of a custom-built Raman spectroscopic probe for diagnosis of early oesophageal neoplasia

    NASA Astrophysics Data System (ADS)

    Almond, L. Max; Hutchings, Jo; Kendall, Catherine; Day, John C. C.; Stevens, Oliver A. C.; Lloyd, Gavin R.; Shepherd, Neil A.; Barr, Hugh; Stone, Nick

    2012-08-01

    We evaluate the potential of a custom-built fiber-optic Raman probe, suitable for in vivo use, to differentiate between benign, metaplastic (Barrett's oesophagus), and neoplastic (dysplastic and malignant) oesophageal tissue ex vivo on short timescales. We measured 337 Raman spectra (λex=830 nm Pex=60 mW t=1 s) using a confocal probe from fresh (298) and snap-frozen (39) oesophageal tissue collected during surgery or endoscopy from 28 patients. Spectra were correlated with histopathology and used to construct a multivariate classification model which was tested using leave one tissue site out cross-validation in order to evaluate the diagnostic accuracy of the probe system. The Raman probe system was able to differentiate, when tested with leave one site out cross-validation, between normal squamous oesophagus, Barrett's oesophagus and neoplasia with sensitivities of (838% to 6%) and specificities of (89% to 99%). Analysis of a two group model to differentiate Barrett's oesophagus and neoplasia demonstrated a sensitivity of 88% and a specificity of 87% for classification of neoplastic disease. This fiber-optic Raman system can provide rapid, objective, and accurate diagnosis of oesophageal pathology ex vivo. The confocal design of this probe enables superficial mucosal abnormalities (metaplasia and dysplasia) to be classified in clinically applicable timescales paving the way for an in vivo trial.

  11. Survey of neoplasia in red kangaroos (Macropus rufus), 1992-2002, in a zoological collection.

    PubMed

    Suedmeyer, Wm Kirk; Johnson, Gayle

    2007-06-01

    An increase in the proportion of cases with neoplasia observed in a collection of captive red kangaroos (Macropus rufus) when compared with historical records and the paucity of reported neoplasms in kangaroos in the literature prompted a 10-yr review of all red kangaroo necropsies. Individual necropsy, medical, and inventory records for all kangaroos at the Kansas City Zoo were reviewed for the period 1 January 1992 to 31 December 2002. Two squamous cell carcinomas of the oral cavity, two mammary gland adenocarcinomas, a multicentric T-cell lymphosarcoma, and one submucosal pyloric lipoma were diagnosed in six of 28 kangaroo deaths. Three neoplasms were diagnosed antemortem. Four of the six neoplasms were considered malignant, and all four had metastasized. The mean age at death was 11 yr. All six animals with neoplasms were female; however, the exhibit population was composed solely of females. Only 11 cases of neoplasia in red kangaroos have been reported in the literature. On the basis of these cases and a review of the literature, the most commonly observed neoplasms in red kangaroos are mammary gland adenocarcinomas and oral squamous cell carcinomas. Common denominators were not identified in these cases, although chronic gingivitis could have been a contributing factor in the development of the oral squamous cell carcinomas. PMID:17679506

  12. Risk for gastric neoplasias in patients with chronic atrophic gastritis: a critical reappraisal.

    PubMed

    Vannella, Lucy; Lahner, Edith; Annibale, Bruno

    2012-03-28

    Chronic atrophic gastritis (CAG) is an inflammatory condition characterized by the loss of gastric glandular structures which are replaced by connective tissue (non-metaplastic atrophy) or by glandular structures inappropriate for location (metaplastic atrophy). Epidemiological data suggest that CAG is associated with two different types of tumors: Intestinal-type gastric cancer (GC) and type I gastric carcinoid (TIGC). The pathophysiological mechanisms which lead to the development of these gastric tumors are different. It is accepted that a multistep process initiating from Helicobacter pylori-related chronic inflammation of the gastric mucosa progresses to CAG, intestinal metaplasia, dysplasia and, finally, leads to the development of GC. The TIGC is a gastrin-dependent tumor and the chronic elevation of gastrin, which is associated with CAG, stimulates the growth of enterochromaffin-like cells with their hyperplasia leading to the development of TIGC. Thus, several events occur in the gastric mucosa before the development of intestinal-type GC and/or TIGC and these take several years. Knowledge of CAG incidence from superficial gastritis, its prevalence in different clinical settings and possible risk factors associated with the progression of this condition to gastric neoplasias are important issues. This editorial intends to provide a brief review of the main studies regarding incidence and prevalence of CAG and risk factors for the development of gastric neoplasias.

  13. Clinical value of tumor doubling estimations in multiple endocrine neoplasia type II.

    PubMed

    Jackson, C E; Talpos, G B; Block, M A; Norum, R A; Lloyd, R V; Tashjian, A H

    1984-12-01

    Experience with children with multiple endocrine neoplasia (MEN) type IIb has emphasized that medullary thyroid cancer (MTC) in MEN IIb is more aggressive than in MEN IIa. Earlier ages of onset and apparently more rapid growth of MTC in MEN IIb suggest that these tumors have earlier ages of conversion to malignant states and/or shorter doubling times. The age at which a hyperplastic C cell becomes a malignant cell and the true doubling time cannot be estimated presently. Maximum volume-doubling times of 35 and 75 days (21 to 26 doublings) were calculated from tumor size and age at operation in five patients with MEN IIb aged 2 to 5 years. Calculations in 20 patients with MEN IIa revealed maximum doubling times of 110 to 440 days, with ages ranging from 7 to 29 years and number of doubling ranging from 18 to 38. Positive provocative calcitonin tests in two adult patients with MEN IIa after 10 to 11 years of repeated negative tests suggest a minimum doubling time of 190 to 210 days. Such experience emphasizes that negative stimulated calcitonin tests less than 11 years after operation do not provide assurance of cures for MTC in MEN IIa although negative tests after more than 5 years for MEN IIb are encouraging. Calculations of volume doublings accounting for various-sized tumors are compatible with Knudson's two-mutational-event theory on the initiation of neoplasia. PMID:6150555

  14. Risk factors for conjunctival squamous cell neoplasia: a matched case-control study

    PubMed Central

    Tulvatana, W; Bhattarakosol, P; Sansopha, L; Sipiyarak, W; Kowitdamrong, E; Paisuntornsug, T; Karnsawai, S

    2003-01-01

    Aims: To identify roles of human papillomavirus (HPV) infection and solar elastosis as the risk factors for conjunctival squamous cell neoplasia (CSCN). Methods: 30 consecutive pathological specimens, ranging from conjunctival intraepithelial neoplasia, carcinoma in situ, to invasive squamous cell carcinoma were retrieved from tissue archives. 30 controls were disease free conjunctiva from age and sex matched patients undergoing extracapsular cataract extraction. Two masked pathologists studied haematoxylin and eosin stains on paraffin embedded conjunctival tissues. Elastic stain for solar elastosis was blindly interpreted in comparison with negative and positive controls. HPV infection was studied by polymerase chain reaction and dot hybridisation. Results: The mean age of CSCN patients was 54.9 years. The male to female ratio was 1:1. Solar elastosis was seen in 53.3% of CSCN and in 3.3% of controls with an odds ratio of 16.0 (95% CI, 2.49 to 670.96; p value = 0.0003). HPV DNA were not detected in any of the specimens. Conclusion: Solar elastosis is much more frequently found in CSCN cases than in their matched controls and is a risk factor for CSCN. These data are insufficient to conclude that HPV infection is a risk factor for CSCN. PMID:12642297

  15. Focal epithelial hyperplasia: Heck disease.

    PubMed

    Cohen, P R; Hebert, A A; Adler-Storthz, K

    1993-09-01

    Two sisters of Mexican ancestry had focal epithelial hyperplasia (FEH). The lesions on the oral mucosa of the older child were initially misinterpreted as representing sexual abuse. Microscopic evaluation of a hematoxylin and eosin-stained section from a lower lip papule demonstrated the histologic features of FEH. Although human papillomavirus (HPV) type 13 and HPV32 have been most consistently present in FEH lesions, types 6, 11, 13, and 32 were not detected in the paraffin-embedded tissue specimen of our patient using an in situ hybridization technique. The lesions persisted or recurred during management using destructive modalities; subsequently, they completely resolved spontaneously.

  16. Focal epithelial hyperplasia in Sweden.

    PubMed

    Axéll, T; Hammarström, L; Larsson, A

    1981-01-01

    A prevalence of 0.11% of focal epithelial hyperplasia (FEH) was found among 20,333 adult Swedes. There was no sex difference, the lesion was most prevalent in age groups above 45 years and the lesion was most frequent on the tongue. The frequency of FEH in 15,132 consecutive routine biopsies was 0.26%. Four FEH-cells were ultrastructurally examined. They exhibited a clear cytoplasm with scattered ribosomes, a peripheral condensation of tonofilaments, a central aggregation of chromatin clumps with loss of nuclear membrane and an accumulation of desmosome fragments. No viral particles could be identified in these FEH-cells.

  17. Undulation Instability of Epithelial Tissues

    NASA Astrophysics Data System (ADS)

    Basan, Markus; Joanny, Jean-François; Prost, Jacques; Risler, Thomas

    2011-04-01

    Treating the epithelium as an incompressible fluid adjacent to a viscoelastic stroma, we find a novel hydrodynamic instability that leads to the formation of protrusions of the epithelium into the stroma. This instability is a candidate for epithelial fingering observed in vivo. It occurs for sufficiently large viscosity, cell-division rate and thickness of the dividing region in the epithelium. Our work provides physical insight into a potential mechanism by which interfaces between epithelia and stromas undulate and potentially by which tissue dysplasia leads to cancerous invasion.

  18. Increased proliferation in atypical hyperplasia/endometrioid intraepithelial neoplasia of the endometrium with concurrent inactivation of ARID1A and PTEN tumour suppressors.

    PubMed

    Ayhan, Ayse; Mao, Tsui-Lien; Suryo Rahmanto, Yohan; Zeppernick, Felix; Ogawa, Hiroshi; Wu, Ren-Chin; Wang, Tian-Li; Shih, Ie-Ming

    2015-07-01

    Uterine endometrioid carcinoma is the most common neoplastic disease in the female genital tract and develops from a common precursor lesion, atypical hyperplasia/endometrioid intraepithelial neoplasia (AH/EIN). Although the genomic landscape of endometrioid carcinoma has been recently revealed, the molecular alterations that contribute to tumour progression from AH/EIN to carcinoma remain to be elucidated. In this study, we used immunohistochemistry to determine if loss of expression of two of the most commonly mutated tumour suppressors in endometrioid carcinoma, PTEN and ARID1A, was associated with increased proliferation in AH/EIN. We found that 80 (70%) of 114 cases exhibited decreased or undetectable PTEN and 17 (15%) of 114 cases had focal loss of ARID1A staining. ARID1A loss was focal, while PTEN loss was diffuse, and all specimens with ARID1A loss had concurrent PTEN loss (p = 0.0003). Mapping the distribution of PTEN and ARID1A staining in the same specimens demonstrated that all AH/EIN areas with ARID1A loss were geographically nested within the areas of PTEN loss. A significant increase in the proliferative activity was observed in areas of AH/EIN with concurrent loss of PTEN and ARID1A compared to immediately adjacent AH/EIN areas showing only PTEN loss. In a cell culture system, co-silencing of ARID1A and PTEN in human endometrial epithelial cells increased cellular proliferation to a greater degree than silencing either ARID1A or PTEN alone. These results suggest an essential gatekeeper role for ARID1A that prevents PTEN inactivation from promoting cellular proliferation in the transition of pre-cancerous lesions to uterine endometrioid carcinoma. PMID:27499903

  19. Canine neoplasia

    PubMed Central

    Prier, J. E.; Brodey, R. S.

    1963-01-01

    The authors review current knowledge of spontaneous neoplasms in the dog. The prevalence of certain types of canine tumour has been studied, and comparisons have been made with the occurrence of similar neoplasms in man. Where there are appropriate analogies between the two species, the dog with spontaneous tumours can be used for studies that are not practicable in man. Nutritional and morphological studies have been done on cells cultured from canine tumours. Some consistency has been demonstrated in the morphology of cultures of different tumours of the same type. Nutritional studies with the transmissible venereal sarcoma of the dog have shown the cells to be subject to a growth-repressing effect by SH-containing amino-acids. Attempts to transmit tumours to other dogs or other species have generally been unsuccessful. A transplantable tumour developed in a mouse injected with non-cellular material from a canine thyroid carcinoma, but it is not certain that the tumour was induced. Cell-culture studies have shown that some tumours yield a factor that is cytopathogenic for normal cells, but none has been shown capable of inducing neoplasms in vivo. ImagesFIG. 3FIG. 4FIG. 5FIG. 1FIG. 2FIG. 6 PMID:14058226

  20. HPV E6/E7 RNA In Situ Hybridization Signal Patterns as Biomarkers of Three-Tier Cervical Intraepithelial Neoplasia Grade

    PubMed Central

    Evans, Mark F.; Peng, Zhihua; Clark, Kelli M.; Adamson, Christine S.-C.; Ma, Xiao-Jun; Wu, Xingyong; Wang, Hongwei; Luo, Yuling; Cooper, Kumarasen

    2014-01-01

    Cervical lesion grading is critical for effective patient management. A three-tier classification (cervical intraepithelial neoplasia [CIN] grade 1, 2 or 3) based on H&E slide review is widely used. However, for reasons of considerable inter-observer variation in CIN grade assignment and for want of a biomarker validating a three-fold stratification, CAP-ASCCP LAST consensus guidelines recommend a two-tier system: low- or high-grade squamous intraepithelial lesions (LSIL or HSIL). In this study, high-risk HPV E6/E7 and p16 mRNA expression patterns in eighty-six CIN lesions were investigated by RNAscope chromogenic in situ hybridization (CISH). Specimens were also screened by immunohistochemistry for p16INK4a (clone E6H4), and by tyramide-based CISH for HPV DNA. HPV genotyping was performed by GP5+/6+ PCR combined with cycle-sequencing. Abundant high-risk HPV RNA CISH signals were detected in 26/32 (81.3%) CIN 1, 22/22 (100%) CIN 2 and in 32/32 (100%) CIN 3 lesions. CIN 1 staining patterns were typified (67.7% specimens) by abundant diffusely staining nuclei in the upper epithelial layers; CIN 2 lesions mostly (66.7%) showed a combination of superficial diffuse-stained nuclei and multiple dot-like nuclear and cytoplasmic signals throughout the epithelium; CIN 3 lesions were characterized (87.5%) by multiple dot-like nuclear and cytoplasmic signals throughout the epithelial thickness and absence/scarcity of diffusely staining nuclei (trend across CIN grades: P<0.0001). These data are consistent with productive phase HPV infections exemplifying CIN 1, transformative phase infections CIN 3, whereas CIN 2 shows both productive and transformative phase elements. Three-tier data correlation was not found for the other assays examined. The dual discernment of diffuse and/or dot-like signals together with the assay’s high sensitivity for HPV support the use of HPV E6/E7 RNA CISH as an adjunct test for deciding lesion grade when CIN 2 grading may be beneficial (e.g. among

  1. [Recent studies on corneal epithelial barrier function].

    PubMed

    Liu, F F; Li, W; Liu, Z G; Chen, W S

    2016-08-01

    Corneal epithelium, the outermost layer of eyeball, is the main route for foreign materials to enter the eye. Under physiological conditions, the corneal epithelial superficial cells form a functionally selective permeability barrier. Integral corneal epithelial barrier function not only ensures the enrolling of nutrients which is required for regular metabolism, but also prevents foreign bodies, or disease-causing microorganism invasion. Recently, a large number of clinical and experimental studies have shown that abnormal corneal epithelial barrier function is the pathological basis for many ocular diseases. In addition, some study found that corneal epithelial barrier constitutes a variety of proteins involved in cell proliferation, differentiation, apoptosis, and a series of physiological and pathological processes. This paper reviewed recent studies specifically on the corneal epithelial barrier, highlights of its structure, function and influence factors. (Chin J Ophthalmol, 2016, 52: 631-635). PMID:27562284

  2. Neoplasias mielodisplásicas o mieloproliferativas (PDQ®)—Versión para profesionales de salud

    Cancer.gov

    Resumen de información revisada por expertos acerca del tratamiento de las neoplasias mielodisplásicas o mieloproliferativas, incluso las leucemias mielomonocítica crónica o juvenil y la LMC atípica.

  3. Pituitary prolactinoma, pancreatic glucagonomas, and aldosterone-producing adrenal cortical adenoma: a suggested variant of multiple endocrine neoplasia type I.

    PubMed

    Gould, E; Albores-Saavedra, J; Shuman, J

    1987-12-01

    A case of a pituitary prolactinoma, pancreatic glucagonoma, and an aldosterone-producing adrenal cortical adenoma coexisting in a 65-year-old man is reported. This case may represent a sporadic variant of the multiple endocrine neoplasia syndrome type I first manifested by hyperaldosteronism.

  4. Cervical Neoplasia-Related Factors and Decreased Prevalence of Uterine Fibroids among a Cohort of African-American Women

    PubMed Central

    Moore, Kristen R.; Smith, Jennifer S.; Laughlin-Tommaso, Shannon K.; Baird, Donna D.

    2013-01-01

    Objective To investigate whether the previously reported inverse association between cervical neoplasia and uterine fibroids is corroborated. Design Cross-sectional analysis of enrollment data from an ongoing prospective study of fibroid development. Setting Detroit, Michigan area. Patients(s) Self-reported data on abnormal Pap smear, colposcopy and cervical treatment were obtained from 1,008 African-American women ages 23-34 with no previous fibroid diagnosis and no reported history of HPV vaccination. Presence of fibroids was assessed at a standardized ultrasound examination. Intervention(s) None. Main Outcome Measure(s) The association between the 3 cervical neoplasia-related variables and presence of fibroids was evaluated with logistic regression to estimate age-adjusted and multivariable-adjusted odds ratios (ORs). Result(s) Of the analysis sample, 46%, 29% and 14% reported a prior abnormal Pap smear, colposcopy and cervical treatment, respectively. Twenty-five percent had fibroids at ultrasound. Those reporting cervical treatment had a 39% [aOR: 0.61, 95%CI (0.38-0.96)] reduction in fibroid risk. Weak non-significant associations were found for abnormal Pap smear and colposcopy. Conclusion(s) Although a protective-type association of cervical neoplasia with uterine fibroids seems counter intuitive, a causal pathway is possible, and the findings are consistent with two prior studies. Further investigation is needed on the relationship between fibroids and cervical neoplasia and HPV-related mechanisms. PMID:24268705

  5. Comparing Benign and Malignant Neoplasia and DSB Induction for Low-and High-LET Radiation

    NASA Astrophysics Data System (ADS)

    Burns, Fredric; (Eric) Tang, Moon-Shong; Wu, Feng

    One-and 2-stage models based on DNA double strand breaks (DSBs) have been developed to describe the dose and LET dependence of cancer induction in rat skin exposed to the Bragg plateau of several ion beams or electron radiation. Data are presented showing that carcinomas (malignant) and fibromas (benign) are induced differently by low and high LET radiation. DSBs are subject to complex repair processes, including homologous and non-homologous end joining, that slowly eliminate broken chromosome ends but at the expense of elevating genomic instability that increases the risk of neoplasia. In this formulation the initial molecular lesion in radiation carcinogenesis is assumed to be a DNA double strand break (DSB). The 2-event model assumes that pairs of DSBs join to create cellular genomic instability that eventually progresses to malignancy. The 1-event model assumes that joining is insignificant but that unrepaired DSBs remain and are sufficiently destabilizing to produce low-grade neoplasias. The respective expected relationships between neoplasia yield (Y), radiation dose (D) and LET (L) are: Y(D) = CLD + BD2 (A) for 2-events and Y(D) = CLD (B) for 1-event. Respective B and C values have been evaluated empirically for carcinomas, fibromas and DSBs, the latter via the -H2Ax technique in surrogate keratinocytes, for several types of radiations, including, 40Ar ions, 56Fe ions, 20Ne ions, protons, electrons and x-rays. Fibromas outnumber carcinomas by about 6:1 but are more sensitive than carcinomas to the cytolethal effect of the radiations. The 2-event model agrees well with carcinoma yields in rat skin but fails to model fibromas correctly. Instead the fibroma yields best fitted with the 1-event model for the high LET ion radiations, but at very low LET (electron radiation), an empirical D3 component becomes apparent which is not currently incorporated into the theoretical model. At higher LET values, the D3 component was not detected. The overall results are

  6. Epithelial Dysplasia in Oral Cavity

    PubMed Central

    Shirani, Samaneh; Kargahi, Neda; Razavi, Sayed Mohammad; Homayoni, Solmaz

    2014-01-01

    Among oral lesions, we encounter a series of malignant epithelial lesions that go through clinical and histopathologic processes in order to be diagnosed. Identifying these processes along with the etiology knowledge of these lesions is very important in prevention and early treatments. Dysplasia is the step preceding the formation of squamous cell carcinoma in lesions which have the potential to undergo dysplasia. Identification of etiological factors, clinical and histopathologic methods has been the topic of many articles. This article, reviews various articles presenting oral cavity dysplasia, new clinical methods of identifying lesions, and the immunohistochemical research which proposes various markers for providing more precise identification of such lesions. This article also briefly analyzes new treatment methods such as tissue engineering. PMID:25242838

  7. Focal epithelial hyperplasia - an update.

    PubMed

    Said, Ahmed K; Leao, Jair C; Fedele, Stefano; Porter, Stephen R

    2013-07-01

    Focal epithelial hyperplasia (FEH) is an asymptomatic benign mucosal disease, which is mostly observed in specific groups in certain geographical regions. FEH is usually a disease of childhood and adolescence and is generally associated with people who live in poverty and of low socioeconomic status. Clinically, FEH is typically characterized by multiple, painless, soft, sessile papules, plaques or nodules, which may coalesce to give rise to larger lesions. Human papillomavirus (HPV), especially genotypes 13 and 32, have been associated and detected in the majority of FEH lesions. The clinical examination and social history often allow diagnosis, but histopathological examination of lesional tissue is usually required to confirm the exact diagnosis. FEH sometimes resolves spontaneously however, treatment is often indicated as a consequence of aesthetic effects or any interference with occlusion. There remains no specific therapy for FEH, although surgical removal, laser excision or possibly topical antiviral agents may be of benefit. There remains no evidence that FEH is potentially malignant.

  8. Bacterial vaginosis and inflammatory response showed association with severity of cervical neoplasia in HPV-positive women.

    PubMed

    de Castro-Sobrinho, Juçara Maria; Rabelo-Santos, Silvia Helena; Fugueiredo-Alves, Rosane Ribeiro; Derchain, Sophie; Sarian, Luis Otávio Z; Pitta, Denise R; Campos, Elisabete A; Zeferino, Luiz Carlos

    2016-02-01

    Vaginal infections may affect susceptibility to and clearance of human papillomavirus (HPV) infection and chronic inflammation has been linked to carcinogenesis. This study aimed to evaluate the association between bacterial vaginosis (BV) and inflammatory response (IR) with the severity of cervical neoplasia in HPV-infected women. HPV DNA was amplified using PGMY09/11 primers and genotyping was performed using a reverse line blot hybridization assay in 211 cervical samples from women submitted to excision of the transformation zone. The bacterial flora was assessed in Papanicolaou stained smears, and positivity for BV was defined as ≥ 20% of clue cells. Present inflammatory response was defined as ≥ 30 neutrophils per field at 1000× magnification. Age higher than 29 years (OR:1.91 95% CI 1.06-3.45), infections by the types 16 and/or 18 (OR:1.92 95% CI 1.06-3.47), single or multiple infections associated with types 16 and/or 18 (OR: 1.92 CI 95% 1.06-3.47), BV (OR: 3.54 95% CI 1.62-7.73) and IR (OR: 6.33 95% CI 3.06-13.07) were associated with severity of cervical neoplasia (CIN 2 or worse diagnoses), while not smoking showed a protective effect (OR: 0.51 95% CI 0.26-0.98). After controlling for confounding factors, BV(OR: 3.90 95% CI 1.64-9.29) and IR (OR: 6.43 95% CI 2.92-14.15) maintained their association with the severity of cervical neoplasia. Bacterial vaginosis and inflammatory response were independently associated with severity of cervical neoplasia in HPV-positive women, which seems to suggest that the microenvironment would relate to the natural history of cervical neoplasia. PMID:26644228

  9. [Combined endoscopic diagnostics with catheter confocal endomicroscopy for gastric neoplasia detection].

    PubMed

    Shuleshova, A G; Zav'ialov, M O; Ul'ianov, D N; Kanareĭtseva, T D

    2014-01-01

    The analysis of combined endoscopic diagnostics with catheter confocal laser endomicroscopy (CCLE) for detection of gastric neoplasia in 103 patients is presented in the article. It was described the main principles of catheter confocal laser endomicroscopy by using of Cellvizio-system ("Mauna Kea Technologies", France). All patients underwent esophagogastroduodenoscopy before catheter confocal laser endomicroscopy. Such modes as HRE-endoscopy, NBI-endoscopy and Zoom-endoscopy were used. It was revealed different neoplastic changes of stomach mucous coat and early cancer forms of stomach in 185 cases. It was noted expediency and high informational content of CCLE which leads to detect the foci of intestinal metaplasia by colonic type, foci of dysplasia and early cancer of stomach mucous coat. The role of conventional morphological study for verification of changes detected with CCLE was shown.

  10. [Combined endoscopic diagnostics with catheter confocal endomicroscopy for gastric neoplasia detection].

    PubMed

    Shuleshova, A G; Zav'ialov, M O; Ul'ianov, D N; Kanareĭtseva, T D

    2014-01-01

    The analysis of combined endoscopic diagnostics with catheter confocal laser endomicroscopy (CCLE) for detection of gastric neoplasia in 103 patients is presented in the article. It was described the main principles of catheter confocal laser endomicroscopy by using of Cellvizio-system ("Mauna Kea Technologies", France). All patients underwent esophagogastroduodenoscopy before catheter confocal laser endomicroscopy. Such modes as HRE-endoscopy, NBI-endoscopy and Zoom-endoscopy were used. It was revealed different neoplastic changes of stomach mucous coat and early cancer forms of stomach in 185 cases. It was noted expediency and high informational content of CCLE which leads to detect the foci of intestinal metaplasia by colonic type, foci of dysplasia and early cancer of stomach mucous coat. The role of conventional morphological study for verification of changes detected with CCLE was shown. PMID:25327669

  11. Protein kinase D1 drives pancreatic acinar cell reprogramming and progression to intraepithelial neoplasia

    NASA Astrophysics Data System (ADS)

    Liou, Geou-Yarh; Döppler, Heike; Braun, Ursula B.; Panayiotou, Richard; Scotti Buzhardt, Michele; Radisky, Derek C.; Crawford, Howard C.; Fields, Alan P.; Murray, Nicole R.; Wang, Q. Jane; Leitges, Michael; Storz, Peter

    2015-02-01

    The transdifferentiation of pancreatic acinar cells to a ductal phenotype (acinar-to-ductal metaplasia, ADM) occurs after injury or inflammation of the pancreas and is a reversible process. However, in the presence of activating Kras mutations or persistent epidermal growth factor receptor (EGF-R) signalling, cells that underwent ADM can progress to pancreatic intraepithelial neoplasia (PanIN) and eventually pancreatic cancer. In transgenic animal models, ADM and PanINs are initiated by high-affinity ligands for EGF-R or activating Kras mutations, but the underlying signalling mechanisms are not well understood. Here, using a conditional knockout approach, we show that protein kinase D1 (PKD1) is sufficient to drive the reprogramming process to a ductal phenotype and progression to PanINs. Moreover, using 3D explant culture of primary pancreatic acinar cells, we show that PKD1 acts downstream of TGFα and Kras, to mediate formation of ductal structures through activation of the Notch pathway.

  12. The management of recurrent and drug-resistant gestational trophoblastic neoplasia (GTN).

    PubMed

    Newlands, E S

    2003-12-01

    Gestational trophoblastic neoplasia (GTN) comprises a spectrum of disease from low-risk disease which can be cured with simple relatively non-toxic treatment, to extremely aggressive tumours which require specialized management. The prognostic variables in patients with GTN are different from those in other gynaecological malignancies, and the major adverse prognostic variables include long interval from antecedent pregnancy, high concentrations of the pregnancy hormone, human chorionic gonadotrophin, metastases in brain and liver and failure of prior treatment. Patients who relapse after their prior treatment can also be categorized into different risk groups. Salvage treatment can vary from single agent actinomycin D to combination chemotherapy and, in selected cases, surgery. With appropriate management, the majority of patients can achieve long-term remission and, in most cases, preserve fertility. The late side-effects of more intensive treatment are a small risk of inducing second tumours and also of bringing forward the age of menopause.

  13. Current concepts in the diagnosis and pathobiology of intraepithelial neoplasia: A review by organ system.

    PubMed

    Voltaggio, Lysandra; Cimino-Mathews, Ashley; Bishop, Justin A; Argani, Pedram; Cuda, Jonathan D; Epstein, Jonathan I; Hruban, Ralph H; Netto, George J; Stoler, Mark H; Taube, Janis M; Vang, Russell; Westra, William H; Montgomery, Elizabeth A

    2016-09-01

    Answer questions and earn CME/CNE In this report, a team of surgical pathologists has provided a review of intraepithelial neoplasia in a host of (but not all) anatomic sites of interest to colleagues in various medical specialties, namely, uterine cervix, ovary, breast, lung, head and neck, skin, prostate, bladder, pancreas, and esophagus. There is more experience with more readily accessible sites (such as the uterine cervix and skin) than with other anatomic sites, and the lack of uniform terminology, together with divergent biology in various sites, makes it difficult to paint a unifying, relevant portrait. The authors' aim was to provide a framework from which to move forward as we care for patients with such precancerous lesions. CA Cancer J Clin 2016;66:408-436. © 2016 American Cancer Society. PMID:27270763

  14. No clinical predictors of intraepithelial neoplasia in HIV-positive patients with external condilomata acuminata

    PubMed Central

    Giacaman, Paula; Martínez, María José; Chnaiderman, Jonas; Ampuero, Sandra; Santander, Ester; Ramis, Claudia; Sazunic, Ivo; Garmendia, María Luisa; Gómez, Orietta

    2011-01-01

    To identify clinical parameters in association with human papilloma virus (HPV) genotypes and histopathology diagnosis in HIV-positive patients with external condylomata acuminata (ECA), 400 Chilean HIV-positive patients were included in the study. Forty-seven patients presented ECA. Clinical parameters and socio demographic data were recorded. Histopathology study and HPV linear array genotyping assay were performed. Intraepithelial neoplasia (IEN) grade 2 or 3 was found in 8.5% of patients, associated to HPV-16. Patients were mainly single, MSM, with history of sexually transmitted disease (STD), multiple sexual partners, receiving antiretroviral therapy and with recurrent lesions. All ECA were mainly perianal, grey or pink colored, exophytic with less than two years evolution. No clinical parameter could predict the development of high grade IEN in HIV patients with ECA. It seems necessary to perform biopsy and genotype all HIV positive patients with ECA. PMID:21799573

  15. Radiation Sensitivity of New Zealand Black Mice and the Development of Autoimmune Disease and Neoplasia

    PubMed Central

    Morton, Jane I.; Siegel, Benjamin V.

    1971-01-01

    Young New Zealand Black (NZB) mice manifested extremely high resistance to the lethal effects of acute exposures to ionizing radiation, with a dose necessary to kill 50% of the animals within 30 days, LD50(30), of 964 roentgens (R) at 30 days of age and of 856 R for 90-day-old mice. In contrast, Coombs' positive 9-month-old NZB mice (with low primary immune response) were highly susceptible (LD50(30) = 543 R), possibly because of anemia-stimulated erythropoiesis leading to a depletion of stem cells. The radiation resistance of young NZB mice, combined with previous observations of their immunologic hyper-responsiveness, support the concept that NZB mice possess an unusually large pool of hematopoietic stem cells, an abnormality which may predispose them to the development of autoimmune disease and neoplasia. PMID:5276282

  16. Streptococcus bovis bacteraemia requires rigorous exclusion of colonic neoplasia and endocarditis.

    PubMed

    Beeching, N J; Christmas, T I; Ellis-Pegler, R B; Nicholson, G I

    1985-08-01

    Twelve patients presented to the hospitals of the Auckland Hospital Board with bacteraemia caused by Streptococcus bovis in the years 1979-84. Ten had endocarditis, affecting homograft valves in two cases and the tricuspid valve in one case. Of nine patients who underwent investigation of the large bowel, only one did not have a colorectal tumour. Three had colonic adenocarcinoma and three had colorectal villous adenoma. Two, including a patient with acute hepatic failure from alcoholic cirrhosis, had colonic adenomata. Colonoscopy provided a tissue diagnosis of colorectal neoplasia despite negative radiological studies in three patients. Bacteraemia due to S. bovis should prompt rigorous investigation to exclude both endocarditis and tumours of the large bowel.

  17. Persistent Human Papillomavirus Infection and Cervical Neoplasia: A Systematic Review and Meta-Analysis

    PubMed Central

    Lindsay, Lisa; Pimenta, Jeanne M.; Poole, Charles; Jenkins, David

    2008-01-01

    Detection of persistent cervical carcinogenic human papillomavirus (HPV) DNA is used as a marker for cervical cancer risk in clinical trials. The authors performed a systematic review and meta-analysis of the association between persistent HPV DNA and high-grade cervical intraepithelial neoplasia (CIN2-3), high-grade squamous intraepithelial lesions (HSIL), and invasive cervical cancer (together designated CIN2-3/HSIL+) to evaluate the robustness of HPV persistence for clinical use. MEDLINE and Current Contents were searched through January 30, 2006. Relative risks (RRs) were stratified by HPV comparison group. Of 2,035 abstracts, 41 studies were eligible for inclusion in the meta-analysis. Over 22,500 women were included in calculation of RRs for persistent HPV DNA detection and cervical neoplasia. RRs ranged from 1.3 (95% confidence interval: 1.1, 1.5) to 813.0 (95% confidence interval: 168.2, 3,229.2) for CIN2-3/HSIL+ versus 12 months), wider testing intervals, CIN2-3/HSIL+, and use of an HPV-negative reference group were consistently associated with higher RRs. Thus, HPV persistence was consistently and strongly associated with CIN2-3/HSIL+, despite wide variation in definitions and study methods. The magnitude of association varied by duration of persistence and testing interval. Precise definition and standardization of HPV testing, sampling procedure, and test interval are needed for reliable clinical testing. These findings validate HPV persistence as a clinical marker and endpoint. PMID:18483125

  18. Human papillomavirus genotypes and their association with cervical neoplasia in a cohort of Western Australian women.

    PubMed

    Brestovac, Brian; Harnett, Gerry B; Smith, David W; Shellam, Geoffrey R; Frost, Felicity A

    2005-05-01

    Human papillomavirus (HPV) is known to be the cause of almost all cervical cancers. The genotypes have been classified into high and low risk types according to their oncogenic potential. However, data for many of the genotypes are limited and some (HPV-26, 53, and 66) have no agreed status. A study was undertaken to determine the HPV genotype distribution in women of Western Australia and the association with cervical neoplasia. Liquid based cervical samples from a cohort of 282 Western Australian women were tested for HPV DNA by PCR followed by DNA sequencing to determine HPV genotypes. HPV-53 and HPV-16 were the most common genotypes found in this population. In addition 86 archived liquid based cervical samples from women with cervical intraepithelial neoplasia grades 1-3 (CIN 1-3) were tested for HPV DNA. Also 32 archived paraffin biopsy samples from women with squamous cell carcinoma were also tested. HPV-16 was the most common genotype found in these samples. Of the cohort of Western Australian women tested, 27% were found to contain HPV and approximately half of these contained known high-risk HPV genotypes, but only 30% of these were types 16 or 18. The data from this study indicate that HPV-53 is not oncogenic based on an R value and odds ratio (OR) of zero. The data also suggest that HPV-73 may be oncogenic, while HPV-66 is unlikely to be. Two high-risk HPV genotypes that are associated with the Asian region (HPV-52 and HPV-58) were found in Western Australian women suggesting a possible epidemiological link between women in these countries.

  19. Annexin A10 expression in colorectal cancers with emphasis on the serrated neoplasia pathway

    PubMed Central

    Bae, Jeong Mo; Kim, Jung Ho; Rhee, Ye-Young; Cho, Nam-Yun; Kim, Tae-You; Kang, Gyeong Hoon

    2015-01-01

    AIM: To validate the utility of Annexin A10 as a surrogate marker of the serrated neoplasia pathway in invasive colorectal cancers (CRCs). METHODS: A total of 1133 primary CRC patients who underwent surgical resection at Seoul National University Hospital between January 2004 and December 2007 were enrolled. Expression of Annexin A10 was evaluated by immunohistochemistry using tissue microarray and paired to our findings on clinicopathologic and molecular characteristics of each individual. CpG island methylator phenotype was determined by MethyLight assay and microsatellite instability was determined by high performance liquid chromatography. KRAS and BRAF mutation status was evaluated by direct sequencing and allele-specific PCR. Univariate and stage-specific survival analyses were performed to reveal the prognostic value of Annexin A10 expression. RESULTS: Annexin A10 expression was observed in 66 (5.8%) of the 1133 patients. Annexin A10 expression was more commonly found in females and was associated with proximal location, ulcerative gross type, advanced T category, N category and TNM stage. CRCs with Annexin A10 expression showed an absence of luminal necrosis, luminal serration and mucin production. CRCs with Annexin A10 expression were associated with CpG island methylator phenotype, microsatellite instability and BRAF mutation. In survival analysis, Annexin A10 expression was associated with poor overall survival and progression-free survival, especially in stage IV CRCs. CONCLUSION: Annexin A10 expression is associated with poor clinical behavior and can be used a supportive surrogate marker of the serrated neoplasia pathway in invasive CRCs. PMID:26361422

  20. Photodynamic therapy of cervical intraepithelial neoplasia grades II and III with Photolon.

    PubMed

    Istomin, Y P; Lapzevich, T P; Chalau, V N; Shliakhtsin, S V; Trukhachova, T V

    2010-09-01

    The objective of the present study was to test in clinics a previously developed novel organ-saving approach for the treatment of CIN using PDT with the photosensitizer Photolon applied in women of a childbearing age with CIN II and III. A total number of 112 patients aged 35.2+/-1.6 with morphologically proven diagnosis of CIN II and III were enrolled into the study. All 112 patients had been observed at least during 1-year follow-up period after PDT. Among them 53 patients (44.1%) were subjected to a dynamic observation for less than 2 years; 29 patients (24.1%) were under the observation for less than 3 years; 13 patients (10.8%) - for 3-4 years and 17 women - for more than 4 years. A complete response represented by the complete regression of neoplastic lesions, which was proved by the results of morphological examinations, was revealed in 104 (92.8%) of treated women. In 3 months after treatment a complete eradication of the HPV infection was proven by PCR-analysis in 47 (53.4%) from 88 patients who have been infected with HPV of a highly oncogenic strains before PDT. PDT with Photolon is an alternative approach for the treatment of cervical intraepithelial neoplasia which can be recommended for women of childbearing age. The simplicity of the procedure as well as its' high therapeutic efficacy defines the reasonability of its' introduction into the clinical practice as a new organ-saving method for the treatment of patients with cervical intraepithelial neoplasia.

  1. The association of uterine cervical microbiota with an increased risk for cervical intraepithelial neoplasia in Korea.

    PubMed

    Oh, H Y; Kim, B-S; Seo, S-S; Kong, J-S; Lee, J-K; Park, S-Y; Hong, K-M; Kim, H-K; Kim, M K

    2015-07-01

    Recent studies have suggested potential roles of the microbiome in cervicovaginal diseases. However, there has been no report on the cervical microbiome in cervical intraepithelial neoplasia (CIN). We aimed to identify the cervical microbiota of Korean women and assess the association between the cervical microbiota and CIN, and to determine the combined effect of the microbiota and human papillomavirus (HPV) on the risk of CIN. The cervical microbiota of 70 women with CIN and 50 control women was analysed using pyrosequencing based on the 16S rRNA gene. The associations between specific microbial patterns or abundance of specific microbiota and CIN risk were assessed using multivariate logistic regression, and the relative excess risk due to interaction (RERI) and the synergy index (S) were calculated. The phyla Firmicutes, Actinobacteria, Bacteroidetes, Proteobacteria, Tenericutes, Fusobacteria and TM7 were predominant in the microbiota and four distinct community types were observed in all women. A high score of the pattern characterized by predominance of Atopobium vaginae, Gardnerella vaginalis and Lactobacillus iners with a minority of Lactobacillus crispatus had a higher CIN risk (OR 5.80, 95% CI 1.73-19.4) and abundance of A. vaginae had a higher CIN risk (OR 6.63, 95% CI 1.61-27.2). The synergistic effect of a high score of this microbial pattern and oncogenic HPV was observed (OR 34.1, 95% CI 4.95-284.5; RERI/S, 15.9/1.93). A predominance of A. vaginae, G. vaginalis and L. iners with a concomitant paucity of L. crispatus in the cervical microbiota was associated with CIN risk, suggesting that bacterial dysbiosis and its combination with oncogenic HPV may be a risk factor for cervical neoplasia.

  2. Histamine acting on H1 receptor promotes inhibition of proliferation via PLC, RAC, and JNK-dependent pathways.

    PubMed

    Notcovich, Cintia; Diez, Federico; Tubio, Maria Rosario; Baldi, Alberto; Kazanietz, Marcelo G; Davio, Carlos; Shayo, Carina

    2010-02-01

    It is well established that histamine modulates cell proliferation through the activation of the histamine H1 receptor (H1R), a G protein-coupled receptor (GPCR) that is known to couple to phospholipase C (PLC) activation via Gq. In the present study, we aimed to determine whether H1R activation modulates Rho GTPases, well-known effectors of Gq/G(11)-coupled receptors, and whether such modulation influences cell proliferation. Experiments were carried out in CHO cells stably expressing H1R (CHO-H1R). By using pull-down assays, we found that both histamine and a selective H1R agonist activated Rac and RhoA in a time- and dose-dependent manner without significant changes in the activation of Cdc42. Histamine response was abolished by the H1R antagonist mepyramine, RGS2 and the PLC inhibitor U73122, suggesting that Rac and RhoA activation is mediated by H1R via Gq coupling to PLC stimulation. Histamine caused a marked activation of serum response factor activity via the H1R, as determined with a serum-responsive element (SRE) luciferase reporter, and this response was inhibited by RhoA inactivation with C3 toxin. Histamine also caused a significant activation of JNK which was inhibited by expression of the Rac-GAP beta2-chimaerin. On the other hand, H1R-induced ERK1/2 activation was inhibited by U73122 but not affected by C3 or beta2-chimaerin, suggesting that ERK1/2 activation was dependent on PLC and independent of RhoA or Rac. [(3)H]-Thymidine incorporation assays showed that both histamine and the H1R agonist inhibited cell proliferation in a dose-dependent manner and that the effect was independent of RhoA but partially dependent on JNK and Rac. Our results reveal that functional coupling of the H1R to Gq-PLC leads to the activation of RhoA and Rac small GTPases and suggest distinct roles for Rho GTPases in the control of cell proliferation by histamine.

  3. Active JNK-dependent secretion of Drosophila Tyrosyl-tRNA synthetase by loser cells recruits haemocytes during cell competition.

    PubMed

    Casas-Tintó, Sergio; Lolo, Fidel-Nicolás; Moreno, Eduardo

    2015-12-11

    Cell competition is a process by which the slow dividing cells (losers) are recognized and eliminated from growing tissues. Loser cells are extruded from the epithelium and engulfed by the haemocytes, the Drosophila macrophages. However, how macrophages identify the dying loser cells is unclear. Here we show that apoptotic loser cells secrete Tyrosyl-tRNA synthetase (TyrRS), which is best known as a core component of the translational machinery. Secreted TyrRS is cleaved by matrix metalloproteinases generating MiniTyr and EMAP fragments. EMAP acts as a guiding cue for macrophage migration in the Drosophila larvae, as it attracts the haemocytes to the apoptotic loser cells. JNK signalling and Kish, a component of the secretory pathway, are autonomously required for the active secretion of TyrRS by the loser cells. Altogether, this mechanism guarantees effective removal of unfit cells from the growing tissue.

  4. Ionizing Radiation Induces Macrophage Foam Cell Formation and Aggregation Through JNK-Dependent Activation of CD36 Scavenger Receptors

    SciTech Connect

    Katayama, Ikuo; Hotokezaka, Yuka; Matsuyama, Toshifumi; Sumi, Tadateru; Nakamura, Takashi

    2008-03-01

    Purpose: Irradiated arteries of cancer patients can be associated with atherosclerosis-like lesions containing cholesterol-laden macrophages (foam cells). Endothelial cell damage by irradiation does not completely explain the foam cell formation. We investigated the possible underlying mechanisms for ionizing radiation (IR)-induced foam cell formation. Methods and Materials: Human peripheral blood monocytes were activated by macrophage colony-stimulating factor and then treated with varying doses of IR in vitro in the absence of endothelial cells. Scavenger receptor expression and foam cell formation of IR-treated macrophages were investigated in the presence or absence of oxidized low-density lipoprotein. We also assessed the importance of mitogen-activated protein kinase activity in the macrophage colony-stimulating factor-activated human monocytes (macrophages) for the foam cell formation. Results: We found that IR treatment of macrophage colony-stimulating factor-activated human peripheral blood monocytes resulted in the enhanced expression of CD36 scavenger receptors and that cholesterol accumulated in the irradiated macrophages with resultant foam cell formation in the presence of oxidized low-density lipoprotein. Furthermore, when cultured on collagen gels, human macrophages formed large foam cell aggregates in response to IR. Antibodies against CD36 inhibited the IR-induced foam cell formation and aggregation, indicating that the IR-induced foam cell formation and the subsequent aggregation are dependent on functional CD36. In addition, we found that IR of human macrophages resulted in c-Jun N-terminal kinase activation and that c-Jun N-terminal kinase inhibition suppressed IR-induced CD36 expression and the subsequent foam cell formation and aggregation. Conclusion: Taken together, these results suggest that IR-induced foam cell formation is mediated by c-Jun N-terminal kinase-dependent CD36 activation.

  5. Active JNK-dependent secretion of Drosophila Tyrosyl-tRNA synthetase by loser cells recruits haemocytes during cell competition.

    PubMed

    Casas-Tintó, Sergio; Lolo, Fidel-Nicolás; Moreno, Eduardo

    2015-01-01

    Cell competition is a process by which the slow dividing cells (losers) are recognized and eliminated from growing tissues. Loser cells are extruded from the epithelium and engulfed by the haemocytes, the Drosophila macrophages. However, how macrophages identify the dying loser cells is unclear. Here we show that apoptotic loser cells secrete Tyrosyl-tRNA synthetase (TyrRS), which is best known as a core component of the translational machinery. Secreted TyrRS is cleaved by matrix metalloproteinases generating MiniTyr and EMAP fragments. EMAP acts as a guiding cue for macrophage migration in the Drosophila larvae, as it attracts the haemocytes to the apoptotic loser cells. JNK signalling and Kish, a component of the secretory pathway, are autonomously required for the active secretion of TyrRS by the loser cells. Altogether, this mechanism guarantees effective removal of unfit cells from the growing tissue. PMID:26658841

  6. Histamine acting on H1 receptor promotes inhibition of proliferation via PLC, RAC, and JNK-dependent pathways

    SciTech Connect

    Notcovich, Cintia; Diez, Federico; Tubio, Maria Rosario; Baldi, Alberto; Kazanietz, Marcelo G.; Davio, Carlos; Shayo, Carina

    2010-02-01

    It is well established that histamine modulates cell proliferation through the activation of the histamine H1 receptor (H1R), a G protein-coupled receptor (GPCR) that is known to couple to phospholipase C (PLC) activation via Gq. In the present study, we aimed to determine whether H1R activation modulates Rho GTPases, well-known effectors of Gq/G{sub 11}-coupled receptors, and whether such modulation influences cell proliferation. Experiments were carried out in CHO cells stably expressing H1R (CHO-H1R). By using pull-down assays, we found that both histamine and a selective H1R agonist activated Rac and RhoA in a time- and dose-dependent manner without significant changes in the activation of Cdc42. Histamine response was abolished by the H1R antagonist mepyramine, RGS2 and the PLC inhibitor U73122, suggesting that Rac and RhoA activation is mediated by H1R via Gq coupling to PLC stimulation. Histamine caused a marked activation of serum response factor activity via the H1R, as determined with a serum-responsive element (SRE) luciferase reporter, and this response was inhibited by RhoA inactivation with C3 toxin. Histamine also caused a significant activation of JNK which was inhibited by expression of the Rac-GAP {beta}2-chimaerin. On the other hand, H1R-induced ERK1/2 activation was inhibited by U73122 but not affected by C3 or {beta}2-chimaerin, suggesting that ERK1/2 activation was dependent on PLC and independent of RhoA or Rac. [{sup 3}H]-Thymidine incorporation assays showed that both histamine and the H1R agonist inhibited cell proliferation in a dose-dependent manner and that the effect was independent of RhoA but partially dependent on JNK and Rac. Our results reveal that functional coupling of the H1R to Gq-PLC leads to the activation of RhoA and Rac small GTPases and suggest distinct roles for Rho GTPases in the control of cell proliferation by histamine.

  7. The sphingolipid degradation product trans-2-hexadecenal induces cytoskeletal reorganization and apoptosis in a JNK-dependent manner.

    PubMed

    Kumar, Ashok; Byun, Hoe-Sup; Bittman, Robert; Saba, Julie D

    2011-07-01

    The bioactive signaling molecule D-erythro-sphingosine-1-phosphate (S1P) is irreversibly degraded by the enzyme S1P lyase (SPL). The reaction of SPL with C18-S1P generates ethanolamine phosphate and a long-chain fatty aldehyde, trans-2-hexadecenal. Modulation of SPL expression in cells and organisms produces significant phenotypes, most of which have been attributed to corresponding changes in S1P-dependent signaling. However, the physiological functions of SPL products are not well understood. In the present study, we explored the biological activities of trans-2-hexadecenal in human and murine cells. We demonstrate that trans-2-hexadecenal causes cytoskeletal reorganization leading to cell rounding, detachment and eventual cell death by apoptosis in multiple cell types, including HEK293T, NIH3T3 and HeLa cells. Trans-2-hexadecenal stimulated a signaling pathway involving MLK3 and the respective phosphorylation of MKK4/7 and JNK, whereas ERK, AKT and p38 were unaffected. Trans-2-hexadecenal-induced apoptosis was accompanied by activation of downstream targets of JNK including c-Jun phosphorylation, cytochrome c release, Bax activation, Bid cleavage and increased translocation of Bim into mitochondria. The antioxidant N-acetylcysteine prevented JNK activation by trans-2-hexadecenal. Further, inhibition of JNK abrogated the cytoskeletal changes and apoptosis caused by trans-2-hexadecenal, whereas Rac1 and RhoA were not involved. In conclusion, our studies provide a new paradigm of sphingolipid signaling by demonstrating for the first time that S1P metabolism generates a bioactive product that induces cellular effects through oxidant stress-dependent MAP kinase cell signaling.

  8. Esophageal epithelial cells acquire functional characteristics of activated myofibroblasts after undergoing an epithelial to mesenchymal transition

    PubMed Central

    Muir, Amanda B.; Dods, Kara; Noah, Yuli; Toltzis, Sarit; Chandramouleeswaran, Prasanna Modayur; Lee, Anna; Benitez, Alain; Bedenbaugh, Adam; Falk, Gary W.; Wells, Rebecca G.; Nakagawa, Hiroshi; Wang, Mei-Lun

    2015-01-01

    Background and Aims Eosinophilic esophagitis (EoE) is an allergic inflammatory disease that leads to esophageal fibrosis and stricture. We have recently shown that in EoE, esophageal epithelial cells undergo an epithelial to mesenchymal transition (EMT), characterized by gain of mesenchymal markers and loss of epithelial gene expression. Whether epithelial cells exposed to profibrotic cytokines can also acquire the functional characteristics of activated myofibroblasts, including migration, contraction, and extracellular matrix deposition, is relevant to our understanding and treatment of EoE-associated fibrogenesis. In the current study, we characterize cell migration, contraction, and collagen production by esophageal epithelial cells that have undergone cytokine-induced EMT in vitro. Methods and Results Stimulation of human non-transformed immortalized esophageal epithelial cells (EPC2-hTERT) with profibrotic cytokines TNFα, TGFβ, and IL1β for three weeks led to acquisition of mesenchymal αSMA and vimentin, and loss of epithelial E-cadherin expression. Upon removal of the profibrotic stimulus, epithelial characteristics were partially rescued. TGFβ stimulation had a robust effect upon epithelial collagen production. Surprisingly, TNFα stimulation had the most potent effect upon cell migration and contraction, exceeding the effects of the prototypical profibrotic cytokine TGFβ. IL1β stimulation alone had minimal effect upon esophageal epithelial migration, contraction, and collagen production. Conclusions Esophageal epithelial cells that have undergone EMT acquire functional characteristics of activated myofibroblasts in vitro. Profibrotic cytokines exert differential effects upon esophageal epithelial cells, underscoring complexities of fibrogenesis in EoE, and implicating esophageal epithelial cells as effector cells in EoE-associated fibrogenesis. PMID:25183431

  9. Airway epithelial cell responses to ozone injury

    SciTech Connect

    Leikauf, G.D.; Simpson, L.G.; Zhao, Qiyu

    1995-03-01

    The airway epithelial cell is an important target in ozone injury. Once activated, the airway epithelium responds in three phases. The initial, or immediate phase, involves activation of constitutive cells, often through direct covalent interactions including the formation of secondary ozonolysis products-hydroxyhydroperoxides, aldehydes, and hydrogen peroxide. Recently, we found hydroxyhydroperoxides to be potent agonists; of bioactive eicosanoid formation by human airway epithelial cells in culture. Other probable immediate events include activation and inactivation of enzymes present on the epithelial surface (e.g., neutral endopeptidase). During the next 2 to 24 hr, or early phase, epithelial cells respond by synthesis and release of chemotactic factors, including chemokines-macrophage inflammatory protein-2, RANTES, and interleukin-8. Infiltrating leukocytes during this period also release elastase, an important agonist of epithelial cell mucus secretion and additional chemokine formation. The third (late) phase of ozone injury is characterized by eosinophil or monocyte infiltration. Cytokine expression leads to alteration of structural protein synthesis, with increases in fibronectin evident by in situ hybridization. Synthesis of epithelial antiproteases, e.g., secretary leukocyte protease inhibitor, may also increase locally 24 to 48 hr after elastase concentrations become excessive. Thus, the epithelium is not merely a passive barrier to ozone injury but has a dynamic role in directing the migration, activating, and then counteracting inflammatory cells. Through these complex interactions, epithelial cells can be viewed as the initiators (alpha) and the receptors (omega) of ozone-induced airway disease. 51 refs., 2 figs., 3 tabs.

  10. Helicobacter spp. infection induces changes in epithelial proliferation and E-cadherin expression in the gastric mucosa of pigs.

    PubMed

    Bracarense, A P F R L; Yamasaki, L; Silva, E O; Oliveira, R L; Alfieri, A A

    2013-11-01

    Gastric disease is common in finishing pigs. Helicobacter spp. infection has been associated with gastritis, gastric ulcers and gastric neoplasia in man and animals. The aim of this study was to determine the effects of Helicobacter spp. infection on gastric morphology in pigs, with emphasis on glandular cell proliferation and E-cadherin expression. Samples of fundus and antrum from 67 finishing pigs were examined microscopically and by immunohistochemistry. The presence of Helicobacter spp. was confirmed by polymerase chain reaction (PCR). Mucosal changes were evaluated and epithelial proliferation was determined by evaluation of the morphometry of nucleolar organizer regions and counting proliferating cell nuclear antigen-positive cells and mitotic figures. Intercellular adhesion was evaluated by E-cadherin expression. In 47 (70%) pigs, Helicobacter spp. infection was confirmed by PCR. Histological findings associated with the infection included mononuclear cell infiltration of the lamina propria and glandular degeneration. There was a significant association between infection and epithelial proliferation in both regions as well as a decrease in the expression of E-cadherin in the antrum.

  11. Derivation and validation of a scoring system to stratify the risk of advanced colorectal neoplasia in asymptomatic adults

    PubMed Central

    Imperiale, Thomas F.; Monahan, Patrick O.; Stump, Timothy E.; Glowinski, Elizabeth A.; Ransohoff, David F.

    2016-01-01

    Background Several methods are recommended equally strongly for colorectal cancer screening in average-risk persons. Risk stratification would enable tailoring of screening within this group, with less invasive tests (sigmoidoscopy or occult blood tests) for lower-risk persons and colonoscopy for higher-risk persons. Objective To create a risk index for advanced neoplasia (colorectal cancer and adenomas or serrated polyps ≥1.0 cm, villous histology, or high-grade dysplasia) anywhere in the colorectum, using the most common risk factors for colorectal neoplasia. Design Cross-sectional study. Setting Multiple endoscopy units, primarily in the Midwest. Patients Persons aged 50 to 80 years undergoing initial screening colonoscopy (December 2004 to September 2011). Measurements Derivation and validation of a risk index based on points from regression coefficients for age, sex, waist circumference, cigarette smoking, and family history of colorectal cancer. Results Among 2993 persons in the derivation set, prevalence of advanced neoplasia was 9.4%. Risks for advanced neoplasia in persons at very low, low, intermediate, and high risk were 1.92% (95% CI, 0.63% to 4.43%), 4.88% (CI, 3.79% to 6.18%), 9.93% (CI, 8.09% to 12.0%), and 24.9% (CI, 21.1% to 29.1%), respectively (P < 0.001). Sigmoidoscopy to the descending colon in the low-risk groups would have detected 51 of 70 (73% [CI, 61% to 83%]) advanced neoplasms. Among 1467 persons in the validation set, corresponding risks for advanced neoplasia were 1.65% (CI, 0.20% to 5.84%), 3.31% (CI, 2.08% to 4.97%), 10.9% (CI, 8.26% to 14.1%), and 22.3% (CI, 16.9% to 28.5%), respectively (P < 0.001). Sigmoidoscopy would have detected 21 of 24 (87.5% [CI, 68% to 97%]) advanced neoplasms. Limitations Split-sample validation; results apply to first-time screening. Conclusion This index stratifies risk for advanced neoplasia among average-risk persons by identifying lower-risk groups for which noncolonoscopy strategies may be

  12. Primary polyoma virus-induced murine thymic epithelial tumors. A tumor model of thymus physiology.

    PubMed Central

    Hoot, G. P.; Kettman, J. R.

    1989-01-01

    Thymic tumors were induced in C3'/Bittner mice by neonatal inoculation with polyoma virus. The objective of this study was to identify the phenotypes of the cells within the tumors and to attempt to determine the origin of the neoplastic cell population(s). At the ultrastructural level, the neoplastic cells resembled normal thymic epithelium with tonofilaments and desmosomes. Immunoperoxidase staining demonstrated the presence of cytokeratin, Iak, -beta 2-microglobulin, -asialo-GM1, the thymic cortical epithelial marker ER-TR4, and the medullary epithelial marker ER-TR5. Islands of normal cortical thymocytes supported by residual normal cortical epithelium and acid phosphatase-positive cortical macrophages were interspersed in the tumors. Residual islands of normal medullary architecture with nonspecific esterase-positive IDCs were rarely identified in tumors. Most lymphocytes in the tumors were normal immature cortical thymocytes with the phenotype Tdt+, PNA+, Thy 1.2bright, Ly-1dull, H-2Kkdull, ThB+, J11d+, and Lyt-2+L3T4+. Lymphocytes in the tumors were steroid-sensitive like normal thymocytes. The proportions of Lyt-2+L3T4- and Lyt-2-L3T4+ cells were generally larger in the tumors than in normal thymus and reflected the higher frequency of lymphocytes in the tumors capable of proliferating in vitro in response to Con A plus IL-2. The data were consistent with the hypothesis that the neoplasia originates from thymic epithelium that is interspersed with normal, developing thymic lymphocytes. Images Figure 4 p[688]-a Figure 1 Figure 2 Figure 3 p687-a Figure 7 PMID:2552813

  13. General Information about Ovarian Epithelial Cancer

    MedlinePlus

    ... Primary Peritoneal Cancer Treatment (PDQ®)–Patient Version General Information About Ovarian Epithelial, Fallopian Tube, and Primary Peritoneal ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

  14. Respiratory epithelial cysts of the orbit.

    PubMed

    Goh, Rachel L Z; Hardy, Thomas G; Williams, Richard A; McNab, Alan A

    2016-10-01

    To describe post-traumatic and congenital respiratory epithelial cysts in the orbit, which are rare lesions with only 5 and 13 published cases, respectively. We reviewed all cases of respiratory epithelial cysts diagnosed at three institutions (two tertiary referral hospitals, one private clinic) between 1995 and 2015. We describe 10 cases of post-traumatic respiratory epithelial cyst (age range 23 - 82), presenting a mean of 17.4 years after their original trauma; and 3 congenital cases (age range 17-34). All but one case underwent surgical excision of the cyst and its lining, along with any surgical implant within the cyst. Two were recurrent after incomplete excision. Three presented with acute infection within the cyst. Respiratory epithelial orbital cysts are probably commoner than the paucity of published reports would suggest. Post-traumatic cysts often present many years after trauma, and may become secondarily infected. Complete surgical removal is recommended to prevent future recurrence. PMID:27468088

  15. [Gingivo-epithelial attachment in dental alloimplants].

    PubMed

    Ermenc, B

    1989-01-01

    In this article the structure of gingivo-epithelial tissue and survey of research about its attachment to the tooth neck are presented. Some further research themes in this important and delicate field of stomatologic implantology are also discussed.

  16. Respiratory epithelial cysts of the orbit.

    PubMed

    Goh, Rachel L Z; Hardy, Thomas G; Williams, Richard A; McNab, Alan A

    2016-10-01

    To describe post-traumatic and congenital respiratory epithelial cysts in the orbit, which are rare lesions with only 5 and 13 published cases, respectively. We reviewed all cases of respiratory epithelial cysts diagnosed at three institutions (two tertiary referral hospitals, one private clinic) between 1995 and 2015. We describe 10 cases of post-traumatic respiratory epithelial cyst (age range 23 - 82), presenting a mean of 17.4 years after their original trauma; and 3 congenital cases (age range 17-34). All but one case underwent surgical excision of the cyst and its lining, along with any surgical implant within the cyst. Two were recurrent after incomplete excision. Three presented with acute infection within the cyst. Respiratory epithelial orbital cysts are probably commoner than the paucity of published reports would suggest. Post-traumatic cysts often present many years after trauma, and may become secondarily infected. Complete surgical removal is recommended to prevent future recurrence.

  17. Clara epithelial cell depletion in the lung.

    PubMed

    Sonar, Sanchaita S; Dudda, Jan C

    2013-01-01

    The bronchial epithelium has been increasingly recognized as an important immunomodulatory compartment in asthma and other lung diseases. Clara cells, which comprise the nonciliated secretory epithelial cells, are an important epithelial cell type with functions in the regulation of lung homeostasis and inflammation. Using naphthalene, Clara cells can be depleted within 24 h and regenerate by 1 month, hence, providing an easy method to study the impact of Clara cells on lung inflammation.

  18. An uncommon focal epithelial hyperplasia manifestation.

    PubMed

    dos Santos-Pinto, Lourdes; Giro, Elisa Maria Aparecida; Pansani, Cyneu Aguiar; Ferrari, Junia; Massucato, Elaine Maria Sgavioli; Spolidório, Luis Carlos

    2009-01-01

    Focal epithelial hyperplasia is a rare, contagious disease associated with infection of the oral mucosa by human papillomavirus types 13 or 32, characterized by multiple soft papules of the same color as the adjacent normal mucosa. It mainly affects the lower lip, buccal mucosa, and tongue. The purpose of this case report was to describe a rare verrucal lesion located in the upper gingiva that was clinically and histologically consistent with focal epithelial hyperplasia. PMID:19941767

  19. Forces driving epithelial wound healing

    PubMed Central

    Veldhuis, Jim H.; Gupta, Mukund; Colombelli, Julien; Muñoz, José J.; Brodland, G. Wayne; Ladoux, Benoit; Trepat, Xavier

    2015-01-01

    A fundamental feature of multicellular organisms is their ability to self-repair wounds through the movement of epithelial cells into the damaged area. This collective cellular movement is commonly attributed to a combination of cell crawling and “purse-string” contraction of a supracellular actomyosin ring. Here we show by direct experimental measurement that these two mechanisms are insufficient to explain force patterns observed during wound closure. At early stages of the process, leading actin protrusions generate traction forces that point away from the wound, showing that wound closure is initially driven by cell crawling. At later stages, we observed unanticipated patterns of traction forces pointing towards the wound. Such patterns have strong force components that are both radial and tangential to the wound. We show that these force components arise from tensions transmitted by a heterogeneous actomyosin ring to the underlying substrate through focal adhesions. The structural and mechanical organization reported here provides cells with a mechanism to close the wound by cooperatively compressing the underlying substrate. PMID:27340423

  20. How do polymeric micelles cross epithelial barriers?

    PubMed

    Pepić, Ivan; Lovrić, Jasmina; Filipović-Grčić, Jelena

    2013-09-27

    Non-parenteral delivery of drugs using nanotechnology-based delivery systems is a promising non-invasive way to achieve effective local or systemic drug delivery. The efficacy of drugs administered non-parenterally is limited by their ability to cross biological barriers, and epithelial tissues particularly present challenges. Polymeric micelles can achieve transepithelial drug delivery because of their ability to be internalized into cells and/or cross epithelial barriers, thereby delivering drugs either locally or systematically following non-parenteral administration. This review discusses the particular characteristics of various epithelial barriers and assesses their potential as non-parenteral routes of delivery. The material characteristics of polymeric micelles (e.g., size, surface charge, and surface decoration) and of unimers dissociated from polymeric micelles determine their interactions (non-specific and/or specific) with mucus and epithelial cells as well as their intracellular fate. This paper outlines the mechanisms governing the major modes of internalization of polymeric micelles into epithelial cells, with an emphasis on specific recent examples of the transport of drug-loaded polymeric micelles across epithelial barriers.

  1. Wound healing of intestinal epithelial cells

    PubMed Central

    Iizuka, Masahiro; Konno, Shiho

    2011-01-01

    The intestinal epithelial cells (IECs) form a selective permeability barrier separating luminal content from underlying tissues. Upon injury, the intestinal epithelium undergoes a wound healing process. Intestinal wound healing is dependent on the balance of three cellular events; restitution, proliferation, and differentiation of epithelial cells adjacent to the wounded area. Previous studies have shown that various regulatory peptides, including growth factors and cytokines, modulate intestinal epithelial wound healing. Recent studies have revealed that novel factors, which include toll-like receptors (TLRs), regulatory peptides, particular dietary factors, and some gastroprotective agents, also modulate intestinal epithelial wound repair. Among these factors, the activation of TLRs by commensal bacteria is suggested to play an essential role in the maintenance of gut homeostasis. Recent studies suggest that mutations and dysregulation of TLRs could be major contributing factors in the predisposition and perpetuation of inflammatory bowel disease. Additionally, studies have shown that specific signaling pathways are involved in IEC wound repair. In this review, we summarize the function of IECs, the process of intestinal epithelial wound healing, and the functions and mechanisms of the various factors that contribute to gut homeostasis and intestinal epithelial wound healing. PMID:21633524

  2. Characterization of prostatic epithelial cell lines derived from transgenic adenocarcinoma of the mouse prostate (TRAMP) model.

    PubMed

    Foster, B A; Gingrich, J R; Kwon, E D; Madias, C; Greenberg, N M

    1997-08-15

    To develop a syngeneic transplantable system to study immunotherapeutic approaches for the treatment of prostate cancer, three cell lines were established from a heterogeneous 32 week tumor of the transgenic adenocarcinoma mouse prostate (TRAMP) model. TRAMP is a transgenic line of C57BL/6 mice harboring a construct comprised of the minimal -426/+28 rat probasin promoter driving prostate-specific epithelial expression of the SV40 large T antigen. TRAMP males develop histological prostatic intraepithelial neoplasia by 8-12 weeks of age that progress to adenocarcinoma with distant metastases by 24-30 weeks of age. The three cell lines (TRAMP-C1, TRAMP-C2, and TRAMP-C3) express cytokeratin, E-cadherin, and androgen receptor by immunohistochemical analysis and do not appear to have a mutated p53. Although TRAMP-C1 and TRAMP-C2 are tumorigenic when grafted into syngeneic C57BL/6 hosts, TRAMP-C3 grows readily in vitro but does not form tumors. The T antigen oncoprotein is not expressed by the cell lines in vitro or in vivo. The rationale for establishing multiple cell lines was to isolate cells representing various stages of cellular transformation and progression to androgen-independent metastatic disease that could be manipulated in vitro and, in combination with the TRAMP model, provide a system to investigate therapeutic interventions, such as immunotherapy prior to clinical trials. PMID:9269988

  3. Warty/basaloid penile intraepithelial neoplasia is more prevalent than differentiated penile intraepithelial neoplasia in nonendemic regions for penile cancer when compared with endemic areas: a comparative study between pathologic series from Paris and Paraguay.

    PubMed

    Soskin, Ana; Vieillefond, Anicke; Carlotti, Agnes; Plantier, Francoise; Chaux, Alcides; Ayala, Gustavo; Velazquez, Elsa F; Cubilla, Antonio L

    2012-02-01

    Penile squamous cell carcinoma shows an ample geographic variation in its prevalence with regions of low (North America, Europe, Japan, and Israel) and high (Africa, Asia, and South America) incidence. However, the geographic variation in the distribution of penile intraepithelial neoplasia is not well established. The aim of the present study was to compare the distribution of in situ and invasive lesions between geographic areas with low (France) and high (Paraguay) penile cancer incidence using a series of consecutive cases. The French series included 86 cases (57 in situ and 29 in situ + invasive squamous cell carcinoma), and the Paraguayan series, 117 cases (31 in situ and 86 in situ + invasive squamous cell carcinoma). Incidence of invasive squamous cell carcinoma in the overall samples was higher in the Paraguayan series (P < .00001). Comparing the Paraguayan and the French series, differentiated penile intraepithelial neoplasia was more prevalent in the former (65.0% versus 19.8%), whereas lesions showing warty and/or basaloid features predominated in the latter (35.0% versus 80.2%) to a significant level (P < .00001). This distinctive pattern of differential distribution was maintained when cases with associated invasive squamous cell carcinoma were excluded. The pattern of distribution of lichen sclerosus was also distinctive, with a significantly higher prevalence in the Paraguayan population when compared with the French series (32.5% versus 12.8%, P = .0015). In summary, there appears to be a distinctive distribution of penile precursor lesions depending on the geographic region in consideration. Penile intraepithelial neoplasia with warty and/or basaloid features predominated in low-incidence areas, whereas differentiated penile intraepithelial neoplasia was more prevalent in endemic regions for penile cancer. Further prospective studies in matched populations and from different geographic regions are needed to further clarify the reasons for this

  4. Usefulness of analysis of p53 alteration and observation of surface microstructure for diagnosis of ulcerative colitis-associated colorectal neoplasia.

    PubMed

    Fujii, S; Fujimori, T; Chiba, T

    2003-03-01

    Patients with ulcerative colitis (UC) have a higher incidence of colorectal cancer. UC-associated colorectal cancer is thought to develop in patients with preexisting UC-associated dysplasia. It is crucial to diagnose UC-associated dysplasia and early stage of cancer in patients with long-standing UC for the purpose of treatment of UC-associated neoplasia. However, it is difficult to detect UC-associated dysplasia and the early stage of cancer endoscopically, and to discriminate these neoplasias from inflammatory regenerative epithelium pathologically. The aim of this study was to clarify whether observation of the surface microstructure could aid in the detection of UC-associated neopalsia, and whether analysis of genetic alterations could be used to discriminate between UC-associated neoplasia and inflammatory regenerative epithelium. Tissue samples were obtained from colectomy specimens from eight cases of UC-associated neoplasia. We examined the surface microstructure of these tissues using stereomicroscopy. We also investigated mutation of K-ras codon 12 using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and alteration of the p53 gene, using immunohistochemistry and PCR-single stranded conformation polymorphism (PCR-SSCP). The surface microstructure of UC-associated neoplasia revealed a packed distribution of oval and/or, club-shaped and/or, branch-shaped pits and a villous appearance. Nuclear accumulation of p53 protein occurred in 59.5% of UC-associated neoplasia. Mutations of the p53 exon 5-8 were detected in 95.2% of UC-associated neoplasia, and these mutations were detected in 92.9% of UC-associated neoplasia that showed negative p53 immunohistochemical staining. Mutations of the p53 exon 5-8 in regenerative epithelium occurred infrequently. The K-ras mutation rate in UC-associated neoplasia was 7.4%. In conclusion, immunohistochemistry and PCR-SSCP analysis of p53 would be useful tools for pathological discrimination

  5. Pure flat epithelial atypia (DIN 1a) on core needle biopsy: study of 60 biopsies with follow-up surgical excision.

    PubMed

    Lavoué, Vincent; Roger, Claire Marie; Poilblanc, Mathieu; Proust, Nicolas; Monghal-Verge, Camille; Sagan, Christine; Tas, Patrick; Mesbah, Habiba; Porée, Philippe; Gay, Catherine; Body, Gilles; Levêque, Jean

    2011-01-01

    Flat epithelial atypia (FEA) is recognized as a precursor of breast cancer and its management (surgical excision or intensive follow-up) remains unclear after diagnosis on core needle biopsy (CNB). The aim of this study was to determine the underestimation rate of pure FEA on CNB and clinical, radiological, and pathological factors of underestimation. 4,062 CNBs from 5 breast cancer centers, performed over a 5-year period, were evaluated. A CNB diagnosis of pure FEA was made in 60 cases (1.5%) (the presence of atypical ductal hyperplasia, lobular neoplasia, radial scars, phyllodes tumor, papillary lesions, ductal carcinoma in situ or invasive carcinoma at CNB were exclusion criteria), and subsequent surgical excision was systematically performed. The histological diagnosis was retrospectively reviewed using standardized criteria and the precise terminology of the World Health Organization by two pathologist physicians. At surgical excision, 6 (10%) ductal carcinoma in situ and 2 (3%) invasive carcinoma were diagnosed. The total underestimation rate was 13%. FEA was associated with atypical ductal hyperplasia in 10 (17%) cases and with lobular neoplasia in 2 (3%) at final pathology. Residual FEA was found in 14 (23%) cases. No clinical, radiological or pathological factors were significantly associated with underestimation. Our data highlight the importance of recognizing and diagnosing FEA in core needle biopsies. Thus, the presence of FEA on CNB, even in isolation, warrants follow-up excision.

  6. Differential Expression of Stem Cell Markers in Ocular Surface Squamous Neoplasia.

    PubMed

    Mishra, Dilip Kumar; Veena, Uppala; Kaliki, Swathi; Kethiri, Abhinav Reddy; Sangwan, Virender S; Ali, Mohammed Hasnat; Naik, Milind N; Singh, Vivek

    2016-01-01

    Ocular Surface Squamous Neoplasm (OSSN) is the neoplasia arising from the conjunctiva, cornea and limbus. OSSN ranges from mild, moderate, severe dysplasia, carcinoma in situ (CIS) to squamous cell carcinoma (SCC). Recent findings on cancer stem cells theory indicate that population of stem-like cell as in neoplasia determines its heterogeneity and complexity leading to varying tumor development of metastatic behavior and recurrence. Cancer stem cell markers are not much explored in the cases of OSSN. In the present study, we aim to evaluate the expression of stem cells using stem cell markers mainly p63, ABCG2, c-KIT (CD117) and CD44 in OSSN tissue, which could have prognostic significance. The present study tries for the first time to explore expression of these stem markers in the cases of OSSN. These cases are subdivided into two groups. One group comprises of carcinoma in situ (n = 6) and the second group comprises of invasive carcinoma (n = 6). The mean age at presentation was 52 years; with 53 years for CIS group and 52 years for SCC group. From each group section from the paraffin block were taken for the IHC staining of p63, c-Kit, ABCG2 and CD44. Our experiments show high expression of P63 and CD44 in the cases of CIN and SCC. Both CIS and SCC displayed positive staining with p63, with more than 80% cells staining positive. However minimal expression of c-kit in both CIN and SCC. But surprisingly we got high expression of ABCG2 in cases of carcinoma in situ as compared to that of invasive squamous cell carcinoma. More than 50% of cells showed CD44 positivity in both CIS and SCC groups. Our results show for the first time that these four stem cells especially the limbal epithelium stem cells play a vital role in the genesis of OSSN but we need to explore more cases before establishing its clinical and biological significance. PMID:27584160

  7. Differential Expression of Stem Cell Markers in Ocular Surface Squamous Neoplasia

    PubMed Central

    Mishra, Dilip Kumar; Veena, Uppala; Kaliki, Swathi; Kethiri, Abhinav Reddy; Sangwan, Virender S.; Ali, Mohammed Hasnat; Naik, Milind N.; Singh, Vivek

    2016-01-01

    Ocular Surface Squamous Neoplasm (OSSN) is the neoplasia arising from the conjunctiva, cornea and limbus. OSSN ranges from mild, moderate, severe dysplasia, carcinoma in situ (CIS) to squamous cell carcinoma (SCC). Recent findings on cancer stem cells theory indicate that population of stem-like cell as in neoplasia determines its heterogeneity and complexity leading to varying tumor development of metastatic behavior and recurrence. Cancer stem cell markers are not much explored in the cases of OSSN. In the present study, we aim to evaluate the expression of stem cells using stem cell markers mainly p63, ABCG2, c-KIT (CD117) and CD44 in OSSN tissue, which could have prognostic significance. The present study tries for the first time to explore expression of these stem markers in the cases of OSSN. These cases are subdivided into two groups. One group comprises of carcinoma in situ (n = 6) and the second group comprises of invasive carcinoma (n = 6). The mean age at presentation was 52 years; with 53 years for CIS group and 52 years for SCC group. From each group section from the paraffin block were taken for the IHC staining of p63, c-Kit, ABCG2 and CD44. Our experiments show high expression of P63 and CD44 in the cases of CIN and SCC. Both CIS and SCC displayed positive staining with p63, with more than 80% cells staining positive. However minimal expression of c-kit in both CIN and SCC. But surprisingly we got high expression of ABCG2 in cases of carcinoma in situ as compared to that of invasive squamous cell carcinoma. More than 50% of cells showed CD44 positivity in both CIS and SCC groups. Our results show for the first time that these four stem cells especially the limbal epithelium stem cells play a vital role in the genesis of OSSN but we need to explore more cases before establishing its clinical and biological significance. PMID:27584160

  8. Evaluation of fecal α1-proteinase inhibitor concentrations in cats with idiopathic inflammatory bowel disease and cats with gastrointestinal neoplasia.

    PubMed

    Burke, Kathrin F; Broussard, John D; Ruaux, Craig G; Suchodolski, Jan S; Williams, David A; Steiner, Jörg M

    2013-05-01

    Idiopathic inflammatory bowel disease (IBD) and gastrointestinal lymphoma are common disorders in cats. The aim of this study was to evaluate fecal α(1)-PI concentrations, a marker of gastrointestinal protein loss, in cats with histopathological evidence of gastrointestinal inflammation or gastrointestinal neoplasia. Fecal and serum samples were obtained from 20 cats with chronic gastrointestinal disease in which endoscopic biopsies were performed. Two groups of cats were assembled based on histopathology: Group A (n = 8), mild to moderate IBD; Group B (n = 12), severe IBD or gastrointestinal neoplasia. Fecal α(1)-PI concentrations and serum concentrations of total protein, albumin, globulin, cobalamin, folate, pancreatic lipase immunoreactivity, and trypsin-like immunoreactivity were determined. Nineteen of the 20 diseased cats had elevated fecal α(1)-PI concentrations, ranging from 1.9 to 233.6 μg/g compared to 20 healthy control cats (normal range: ≤1.6 μg/g). Fecal α(1)-PI concentrations were statistically significantly different between healthy cats and cats of Group A (median: 3.9 μg/g, range: 1.3-9.2 μg/g, P < 0.001) or cats of Group B (median: 20.6 μg/g, 4.3-233.6 μg/g; P < 0.001), and between cats of Groups A and B (P < 0.01). Hypoalbuminemia, hypoproteinemia, and hypocobalaminemia were detected in 88%, 83%, and 56% of the diseased cats, respectively. This study suggests that increased fecal α(1)-PI concentrations in association with low serum albumin and total protein concentrations may be a common finding in cats with IBD or gastrointestinal neoplasia. Furthermore, fecal α(1)-PI concentrations appear to be higher in cats with severe IBD or confirmed gastrointestinal neoplasia when compared to cats with mild to moderate IBD. PMID:23231864

  9. Intestinal epithelial dysplasia (tufting enteropathy).

    PubMed

    Goulet, Olivier; Salomon, Julie; Ruemmele, Frank; de Serres, Natacha Patey-Mariaud; Brousse, Nicole

    2007-01-01

    Intestinal epithelial dysplasia (IED), also known as tufting enteropathy, is a congenital enteropathy presenting with early-onset severe intractable diarrhea causing sometimes irreversible intestinal failure. To date, no epidemiological data are available, however, the prevalence can be estimated at around 1/50,000-100,000 live births in Western Europe. The prevalence seems higher in areas with high degree of consanguinity and in patients of Arabic origin. Infants develop within the first days after birth a watery diarrhea persistent in spite of bowel rest and parenteral nutrition. Some infants are reported to have associated choanal rectal or esophageal atresia. IED is thought to be related to abnormal enterocytes development and/or differentiation. Nonspecific punctuated keratitis was reported in more than 60% of patients. Histology shows various degree of villous atrophy, with low or without mononuclear cell infiltration of the lamina propria but specific histological abnormalities involving the epithelium with disorganization of surface enterocytes with focal crowding, resembling tufts. Several associated specific features were reported, including abnormal deposition of laminin and heparan sulfate proteoglycan (HSPG) in the basement membrane, increased expression of desmoglein and ultrastructural changes in the desmosomes, and abnormal distribution of alpha2beta1 integrin adhesion molecules. One model of transgenic mice in which the gene encoding the transcription factor Elf3 is disrupted have morphologic features resembling IED. Parental consanguinity and/or affected siblings suggest an autosomal recessive transmission but the causative gene(s) have not been yet identified making prenatal diagnosis unavailable. Some infants have a milder phenotype than others but in most patients, the severity of the intestinal malabsorption even with enteral feeding make them totally dependent on daily long-term parenteral nutrition with a subsequent risk of complications

  10. Epithelial Ovarian Cancer Experimental Models

    PubMed Central

    Lengyel, E; Burdette, JE; Kenny, HA; Matei, D; Pilrose, J; Haluska, P.; Nephew, KP; Hales, DB; Stack, MS

    2014-01-01

    Epithelial ovarian cancer (OvCa) is associated with high mortality and, as the majority (>75%) of women with OvCa have metastatic disease at the time of diagnosis, rates of survival have not changed appreciably over 30 years. A mechanistic understanding of OvCa initiation and progression is hindered by the complexity of genetic and/or environmental initiating events and lack of clarity regarding the cell(s) or tissue(s) of origin. Metastasis of OvCa involves direct extension or exfoliation of cells and cellular aggregates into the peritoneal cavity, survival of matrix-detached cells in a complex ascites fluid phase, and subsequent adhesion to the mesothelium lining covering abdominal organs to establish secondary lesions containing host stromal and inflammatory components. Development of experimental models to recapitulate this unique mechanism of metastasis presents a remarkable scientific challenge and many approaches used to study other solid tumors (lung, colon, and breast, for example) are not transferable to OvCa research given the distinct metastasis pattern and unique tumor microenvironment. This review will discuss recent progress in the development and refinement of experimental models to study OvCa. Novel cellular, three-dimensional organotypic, and ex vivo models are considered and the current in vivo models summarized. The review critically evaluates currently available genetic mouse models of OvCa, the emergence of xenopatients, and the utility of the hen model to study OvCa prevention, tumorigenesis, metastasis, and chemoresistance. As these new approaches more accurately recapitulate the complex tumor microenvironment, it is predicted that new opportunities for enhanced understanding of disease progression, metastasis and therapeutic response will emerge. PMID:23934194

  11. The secretome of alginate-encapsulated limbal epithelial stem cells modulates corneal epithelial cell proliferation.

    PubMed

    Wright, Bernice; Hopkinson, Andrew; Leyland, Martin; Connon, Che J

    2013-01-01

    Limbal epithelial stem cells may ameliorate limbal stem cell deficiency through secretion of therapeutic proteins, delivered to the cornea in a controlled manner using hydrogels. In the present study the secretome of alginate-encapsulated limbal epithelial stem cells is investigated. Conditioned medium was generated from limbal epithelial stem cells encapsulated in 1.2% (w/v) calcium alginate gels. Conditioned medium proteins separated by 1-D gel electrophoresis were visualized by silver staining. Proteins of interest including secreted protein acidic and rich in cysteine, profilin-1, and galectin-1 were identified by immunoblotting. The effect of conditioned medium (from alginate-encapsulated limbal epithelial stem cells) on corneal epithelial cell proliferation was quantified and shown to significantly inhibit (P≤0.05) their growth. As secreted protein acidic and rich in cysteine was previously reported to attenuate proliferation of epithelial cells, this protein may be responsible, at least in part, for inhibition of corneal epithelial cell proliferation. We conclude that limbal epithelial stem cells encapsulated in alginate gels may regulate corneal epithelialisation through secretion of inhibitory proteins.

  12. Volumetric laser endomicroscopy can target neoplasia not detected by conventional endoscopic measures in long segment Barrett’s esophagus

    PubMed Central

    Trindade, Arvind J.; George, Benley J.; Berkowitz, Joshua; Sejpal, Divyesh V.; McKinley, Matthew J.

    2016-01-01

    Methods and study aims: The incidence of esophageal cancer is rising despite increased surveillance efforts. Volumetric laser endomicroscopy (VLE) is a new endoscopic imaging tool that can allow for targeted biopsy of neoplasia in Barrett’s esophagus. We report a series of 6 patients with long-segment Barrett’s esophagus ( > 3 cm), who underwent a session of endoscopy with volumetric laser endomicroscopy, after a separate prior session of standard high-definition endoscopy with narrow band imaging (NBI) and random biopsies that did not reveal neoplasia. In all six patients, the first endoscopy was the index endoscopy diagnosing the Barrett’s esophagus. All VLE exams were performed within 6 months of the previous endoscopy. In five patients, VLE-targeted biopsy resulted in upstaged disease/diagnosed dysplasia that then qualified the patient for endoscopic ablation therapy. In one patient, VLE localized a focus of intramucosal cancer that allowed for curative endoscopic mucosal resection. This case series shows that endoscopy with VLE can target neoplasia that cannot be localized by high-definition endoscopy with NBI and random biopsies. PMID:27004250

  13. Scrib is Required for Epithelial Cell Identity and Prevents Epithelial To Mesenchymal Transition in the Mouse

    PubMed Central

    Yamben, Idella F.; Rachel, Rivka A.; Shatadal, Shalini; Copeland, Neal G.; Jenkins, Nancy A.; Warming, Soren; Griep, Anne E.

    2013-01-01

    The integrity and function of epithelial tissues depends on the establishment and maintenance of defining characteristics of epithelial cells, cell-cell adhesion and cell polarity. Disruption of these characteristics can lead to the loss of epithelial identity through a process called epithelial to mesenchymal transition (EMT), which can contribute to pathological conditions such as tissue fibrosis and invasive cancer. In invertebrates, the epithelial polarity gene scrib plays a critical role in establishing and maintaining cell adhesion and polarity. In this study we asked if the mouse homolog, Scrib, is required for establishment and/or maintenance of epithelial identity in vivo. To do so, we conditionally deleted Scrib in the head ectoderm tissue that gives rise to both the ocular lens and the corneal epithelium. Deletion of Scrib in the lens resulted in a change in epithelial cell shape from cuboidal to flattened and elongated. Early in the process, the cell adhesion protein, E-cadherin, and apical polarity protein, ZO-1, were downregulated and the myofibroblast protein, αSMA, was upregulated, suggesting EMT was occurring in the Scrib deficient lenses. Correlating temporally with the upregulation of αSMA, Smad3 and Smad4, TGFβ signaling intermediates, accumulated in the nucleus and Snail, a TGFβ target and transcriptional repressor of the gene encoding E-cadherin, was upregulated. Pax6, a lens epithelial transcription factor required to maintain lens epithelial cell identity also was downregulated. Loss of Scrib in the corneal epithelium also led to molecular changes consistent with EMT, suggesting that the effect of Scrib deficiency was not unique to the lens. Together, these data indicate that mammalian Scrib is required to maintain epithelial identity and that loss of Scrib can culminate in EMT, mediated, at least in part, through TGFβ signaling. PMID:24095903

  14. Incisal margin condition after LEEP for cervical intraepithelial neoplasia patients and prognosis

    PubMed Central

    Chen, Hong; Liu, Xiufeang; Xu, Lina

    2016-01-01

    The aim of the study was to examine the relationship between incisal condition after loop electrosurgical excision procedure (LEEP) operation for cervical intraepithelial neoplasia (CIN) patients and prognosis. A study of high-risk incisal margin positive cases was also performed. We compared the differences in the prognosis of the 1-year follow-up visit in the 120 CIN patients admitted to the hospital during the period from April 2013 to April 2014. A total of 43 cases of positive incisal margin (35.8%), and 77 negative cases were included in the study. The differences in age, course of disease, and CIN level between the two groups showed no statistical significance (P>0.05). In the positive group, the positive ratio was significantly higher than that of the negative group (P<0.05). The positive incisal margin showed a significant positive correlation with human papillomavirus (HPV) positivity (r=0.327, P=0.035). The condition of most patients with positive incisal margin and HPV was critical, which was followed by positive incisal margin and negative HPV. The patients with the best prognosis were those with significant negative incisal margin as well as HPV (P<0.05). In conclusion, the positive incisal margin after LEEP operation was associated with relapse of the disease. Thus, considering the HPV test into consideration is valuable for the prognosis of the disease. PMID:27446314

  15. Detection of cervical intraepithelial neoplasias and cancers in cervical tissue by in vivo light scattering.

    PubMed

    Mourant, Judith R; Bocklage, Thérese J; Powers, Tamara M; Greene, Heather M; Dorin, Maxine H; Waxman, Alan G; Zsemlye, Meggan M; Smith, Harriet O

    2009-10-01

    OBJECTIVE: To examine the utility of in vivo elastic light scattering measurements to identify cervical intraepithelial neoplasias (CIN) 2/3 and cancers in women undergoing colposcopy and to determine the effects of patient characteristics such as menstrual status on the elastic light scattering spectroscopic measurements. MATERIALS AND METHODS: A fiber optic probe was used to measure light transport in the cervical epithelium of patients undergoing colposcopy. Spectroscopic results from 151 patients were compared with histopathology of the measured and biopsied sites. A method of classifying the measured sites into two clinically relevant categories was developed and tested using five-fold cross-validation. RESULTS: Statistically significant effects by age at diagnosis, menopausal status, timing of the menstrual cycle, and oral contraceptive use were identified, and adjustments based upon these measurements were incorporated in the classification algorithm. A sensitivity of 77±5% and a specificity of 62±2% were obtained for separating CIN 2/3 and cancer from other pathologies and normal tissue. CONCLUSIONS: The effects of both menstrual status and age should be taken into account in the algorithm for classifying tissue sites based on elastic light scattering spectroscopy. When this is done, elastic light scattering spectroscopy shows good potential for real-time diagnosis of cervical tissue at colposcopy. Guiding biopsy location is one potential near-term clinical application area, while facilitating "see and treat" protocols is a longer term goal. Improvements in accuracy are essential. PMID:20694193

  16. How significant is the association between metabolic syndrome and prevalence of colorectal neoplasia?

    PubMed Central

    Suchanek, Stepan; Grega, Tomas; Ngo, Ondrej; Vojtechova, Gabriela; Majek, Ondrej; Minarikova, Petra; Brogyuk, Nagyija; Bunganic, Bohus; Seifert, Bohumil; Dusek, Ladislav; Zavoral, Miroslav

    2016-01-01

    The incidence and prevalence of metabolic syndrome (MS) and colorectal cancer (CRC) has been rising in developed countries. The association between these two diseases has been widely studied and reported. Less evidence is available about the relationship between MS and CRC precancerous lesions (adenomatous polyps, adenomas). The aim of this paper is to present an overview of our scientific understanding of that topic and its implication in clinical practice. One of the principal goals of current CRC secondary prevention efforts is to detect and remove the precancerous lesions in individuals with an average CRC risk to prevent the development of invasive cancer. MS is not currently considered a high-risk CRC factor and is therefore not included in the guidelines of organized screening programs. However, in light of growing scientific evidence, the approach to patients with MS should be changed. Metabolic risk factors for the development of adenomas and cancers are the same - obesity, impaired glucose tolerance, dyslipidemia, hypertension, cardiovascular diseases and diabetes mellitus type 2. Therefore, the key issue in the near future is the development of a simple scoring system, easy to use in clinical practice, which would identify individuals with high metabolic risk of colorectal neoplasia and would be used for individual CRC secondary prevention strategies. Currently, such scoring systems have been published based on Asian (Asia-Pacific Colorectal Screening Score; APCS) and Polish populations.

  17. How significant is the association between metabolic syndrome and prevalence of colorectal neoplasia?

    PubMed

    Suchanek, Stepan; Grega, Tomas; Ngo, Ondrej; Vojtechova, Gabriela; Majek, Ondrej; Minarikova, Petra; Brogyuk, Nagyija; Bunganic, Bohus; Seifert, Bohumil; Dusek, Ladislav; Zavoral, Miroslav

    2016-09-28

    The incidence and prevalence of metabolic syndrome (MS) and colorectal cancer (CRC) has been rising in developed countries. The association between these two diseases has been widely studied and reported. Less evidence is available about the relationship between MS and CRC precancerous lesions (adenomatous polyps, adenomas). The aim of this paper is to present an overview of our scientific understanding of that topic and its implication in clinical practice. One of the principal goals of current CRC secondary prevention efforts is to detect and remove the precancerous lesions in individuals with an average CRC risk to prevent the development of invasive cancer. MS is not currently considered a high-risk CRC factor and is therefore not included in the guidelines of organized screening programs. However, in light of growing scientific evidence, the approach to patients with MS should be changed. Metabolic risk factors for the development of adenomas and cancers are the same - obesity, impaired glucose tolerance, dyslipidemia, hypertension, cardiovascular diseases and diabetes mellitus type 2. Therefore, the key issue in the near future is the development of a simple scoring system, easy to use in clinical practice, which would identify individuals with high metabolic risk of colorectal neoplasia and would be used for individual CRC secondary prevention strategies. Currently, such scoring systems have been published based on Asian (Asia-Pacific Colorectal Screening Score; APCS) and Polish populations. PMID:27688652

  18. Grading of cervical intraepithelial neoplasia using spatial frequency for optical histology

    NASA Astrophysics Data System (ADS)

    Pu, Yang; Jagtap, Jaidip; Pradhan, Asima; Alfano, Robert R.

    2014-03-01

    It is important to detect cervical dysplasia, Cervical Intraepithelial Neoplasia (CIN). CIN is the potentially premalignant and abnormal squamous cells on surface of cervix. In this study, the spatial frequency spectra of pre-cancer cervical tissues are used to detect differences among different grades of human cervical tissues. Seven sets of thick tissue sections of human cervix of normal, CIN 1, CIN 2, and CIN 3 tissues are studied. The confocal microscope images of the stromal region of normal and CIN human tissues were analyzed using Fast Fourier Transform (FFT) to generate the spatial spectra. It is observed that higher frequency components exist in CIN tissues than those in normal tissue, as well as those in higher grade CIN tissue than those in lower grade CIN tissue. The width of the spatial frequency of different types of tissues is used to create a criterion for CIN grading by training a support vector machine (SVM) classifier. The results show that the randomness of tissue structures from normal to different stages of precancer in cervical tissue can be recognized by fingerprints of the spatial frequency. The efficacy of spatial frequency analysis for CIN grading is evaluated as excellent since high AUC (area under the ROC curve), sensitivity and specificity are obtained by the statistics study. This works lays the foundation of using spatial frequency spectra for a histology evaluation.

  19. Disseminated neoplasia causes changes in ploidy and apoptosis frequency in cockles Cerastoderma edule.

    PubMed

    Díaz, S; Villalba, A; Insua, A; Soudant, P; Fernández-Tajes, J; Méndez, J; Carballal, M J

    2013-07-01

    A proliferative disease, usually referred as disseminated neoplasia (DN), shows high prevalence in some cockle Cerastoderma edule beds of Galicia (NW Spain). Chromosome counts, examination of chromosome morphology, DNA quantification by flow cytometry and estimation of apoptosis frequency by TUNEL assay and flow cytometry were performed in cockles with different DN severity. Metaphases obtained from gills of DN-affected cockles displayed a chromosome number ranging from 41 to 145, while normal number is 38; changes in chromosome morphology were also evident, with numerous microchromosomes occurring. Haemolymph flow cytometry analysis revealed difference in DNA content between healthy and DN-affected cockles. Aneuploid peaks ranged from 1.3n to 8.9n. Apoptosis frequency was determined on histological sections (TUNEL assay) and haemolymph samples (flow cytometry). Both techniques revealed neoplastic cells in apoptosis. The higher DN severity, the lower the percentage of apoptotic cells. According to flow cytometry results, the negative association between DN severity and apoptosis frequency only affected the neoplastic cells, whereas DN did not significantly affect the percentage of apoptotic hyalinocytes or apoptotic granulocytes.

  20. Disseminated neoplasia in cockles Cerastoderma edule: ultrastructural characterisation and effects on haemolymph cell parameters.

    PubMed

    Díaz, Seila; Renault, Tristan; Villalba, Antonio; Carballal, María Jesús

    2011-09-01

    Disseminated neoplasia (DN) has been detected in cockles from various beds in Galicia (NW Spain). A study was performed to characterise cockle neoplastic cell ultrastructure and to evaluate the effect of this disease at different severity stages on various haemolymph cell parameters. Examination of cockle neoplastic cells with transmission electron microscopy (TEM) showed round shapes and a lack of pseudopods, a high nucleus:cytoplasm diameter ratio, Golgi complexes, abundant mitochondria, ribosomes, and numerous endoplasmic reticulum tubes and electron-lucent vesicles. Various haemolymph cell parameters (cell mortality, non-specific esterase and lysosome biovolume, reactive oxygen intermediates [ROI] production, phagocytosis ability, intracellular Ca2+ and actin levels) were compared between DN severity categories by flow cytometry; haemocyte mortality, non-specific esterase activities and lysosome biovolume were found to be higher with increasing DN severity. The phagocytic ability of neoplastic cells was sharply reduced with regard to haemocytes. The cytoplasmic-free Ca2+ level was higher and actin content lower in haemolymph cells of diseased cockles compared to unaffected ones. A significant increase in ROI production was detected in later stages of disease progression.

  1. Cytomorphology and PCNA expression pattern in bivalves Mytilus galloprovincialis and Cerastoderma edule with haemic neoplasia.

    PubMed

    Carella, Francesca; Figueras, Antonio; Novoa, Beatriz; De Vico, Gionata

    2013-07-01

    Haemic neoplasia (HN) is a pathologic condition reported in several bivalve species in different geographic areas. In this study we describe the cytomorphological features and the proliferative behaviour, assessed by the proliferating cell nuclear antigen (PCNA), of HN in common cockle Cerastoderma edule and Mediterranean mussel Mytilus galloprovicialis. In mussels the presence of at least 5 types of atypical haemocytes was detected, including A- and B-type cells, previously described in M. edulis and Mytilus sp., with predominance of A-type cells in early phases of the disease and B-type cells in more advanced stages. PCNA immunostaining was positive for 97 to 100% of the neoplastic cells, with both cytoplasmic (A cells) and nuclear patterns (B cells). Conversely, in C. edule there was no distinctive morphological cell sub-population, and staining atypical haemocytes with PCNA (range 93 to 100%) showed nuclear expression in early phases of disease and cytoplasmic expression in more advanced stages. The above findings suggest distinct histo-pathogenetic pathways for HN in mussels and common cockles.

  2. Comparison between two portable devices for widefield PpIX fluorescence during cervical intraepithelial neoplasia treatment

    NASA Astrophysics Data System (ADS)

    Carbinatto, Fernanda M.; Inada, Natalia Mayumi; Lombardi, Welington; Cossetin, Natália Fernandez; Varoto, Cinthia; Kurachi, Cristina; Bagnato, Vanderlei Salvador

    2015-06-01

    The use of portable electronic devices, in particular mobile phones such as smartphones is increasing not only for all known applications, but also for diagnosis of diseases and monitoring treatments like topical Photodynamic Therapy. The aim of the study is to evaluate the production of the photosensitizer Protoporphyrin IX (PpIX) after topical application of a cream containing methyl aminolevulinate (MAL) in the cervix with diagnosis of Cervical Intraepithelial Neoplasia (CIN) through the fluorescence images captured after one and three hours and compare the images using two devices (a Sony Xperia® mobile and an Apple Ipod®. Was observed an increasing fluorescence intensity of the cervix three hours after cream application, in both portable electronic devices. However, because was used a specific program for the treatment of images using the Ipod® device, these images presented better resolution than observed by the Sony cell phone without a specific program. One hour after cream application presented a more selective fluorescence than the group of three hours. In conclusion, the use of portable devices to obtain images of PpIX fluorescence shown to be an effective tool and is necessary the improvement of programs for achievement of better results.

  3. The incidence and histological characteristics of intratubular germ cell neoplasia in postpubertal cryptorchid testis

    PubMed Central

    Ryang, Seung Hoon; Jung, Jae Hung; Eom, Minseob; Song, Jae Mann; Chung, Hyun Chul; Chae, Yunbyung; Lee, Chang Min

    2015-01-01

    Purpose It is well known that testicular germ cell tumors arise with increased frequency in patients with cryptorchidism. In addition, intratubular germ cell neoplasia (ITGCN) is a precursor lesion to testicular germ cell tumor. Approximately 50% of patients with ITGCN will develop an invasive of testicular germ cell tumors within 5 years. Therefore, we evaluated that the incidence of ITGCN in postpubertal cryptorchidism. Materials and Methods Between January 2002 and August 2012, orchiectomy specimens from 31 postpubertalpatients (aged 12 or over) with cryptorchid testis were reviewed. The specimens were evaluated for ITGCN using immunohistochemical stains of placental-like alkaline phosphatase and Oct 3/4 with routine hematoxylin-eosin stain. Additionally, the degree of spermatogenesis was assessed using the Johnsen score. Results Mean age was 34 years (range, 17 to 74 years) at surgery. All patients were diagnosed as unilateral cryptorchidism. One patient (3.2%) of 20-year-old had ITGCN in surgical specimen with all positive markers. Histological assessment of spermatogenesis showed that mean Johnsen score was 3.42 (range, 1 to 9). Majority of patients (27 of 31) presented impaired spermatogenesis with low Johnsen score lesser than 5. Conclusions Considering the risk of malignancy and low spermatogenesis, we should perform immunohistochemical stains and discuss preventative orchiectomy for the postpubertal cryptorchidism. PMID:26175870

  4. Multiple Endocrine Neoplasia Type 1 Presenting as Hypoglycemia due to Insulinoma

    PubMed Central

    Jeong, Hwal Rim; Shim, Young Seok; Lee, Hae Sang

    2016-01-01

    Multiple endocrine neoplasia (MEN) mutation is an autosomal dominant disorder characterized by the occurrence of parathyroid, pancreatic islet, and anterior pituitary tumors. The incidence of insulinoma in MEN is relatively uncommon, and there have been a few cases of MEN manifested with insulinoma as the first symptom in children. We experienced a 9-year-old girl having a familial MEN1 mutation. She complained of dizziness, occasional palpitation, weakness, hunger, sweating, and generalized tonic-clonic seizure that lasted for 5 minutes early in the morning. At first, she was only diagnosed with insulinoma by abdominal magnetic resonance images of a 1.3 x 1.5 cm mass in the pancreas and high insulin levels in blood of the hepatic vein, but after her father was diagnosed with MEN1. We found she had familial MEN1 mutation, and she recovered hyperinsulinemic hypoglycemia after enucleation of the mass. Therefore, the early genetic identification of MEN1 mutation is considerable for children with at least one manifestation. PMID:27247513

  5. Multiple Endocrine Neoplasia Type 1 Presenting as Hypoglycemia due to Insulinoma.

    PubMed

    Kwon, Eun Byul; Jeong, Hwal Rim; Shim, Young Seok; Lee, Hae Sang; Hwang, Jin Soon

    2016-06-01

    Multiple endocrine neoplasia (MEN) mutation is an autosomal dominant disorder characterized by the occurrence of parathyroid, pancreatic islet, and anterior pituitary tumors. The incidence of insulinoma in MEN is relatively uncommon, and there have been a few cases of MEN manifested with insulinoma as the first symptom in children. We experienced a 9-year-old girl having a familial MEN1 mutation. She complained of dizziness, occasional palpitation, weakness, hunger, sweating, and generalized tonic-clonic seizure that lasted for 5 minutes early in the morning. At first, she was only diagnosed with insulinoma by abdominal magnetic resonance images of a 1.3 x 1.5 cm mass in the pancreas and high insulin levels in blood of the hepatic vein, but after her father was diagnosed with MEN1. We found she had familial MEN1 mutation, and she recovered hyperinsulinemic hypoglycemia after enucleation of the mass. Therefore, the early genetic identification of MEN1 mutation is considerable for children with at least one manifestation. PMID:27247513

  6. In vivo Diagnosis of Cervical Intraepithelial Neoplasia Using 337-nm- Excited Laser-Induced Fluorescence

    NASA Astrophysics Data System (ADS)

    Ramanujam, N.; Mitchell, M. F.; Mahadevan, A.; Warren, S.; Thomsen, S.; Silva, E.; Richards-Kortum, R.

    1994-10-01

    Laser-induced fluorescence at 337-nm excitation was used in vivo to differentiate neoplastic [cervical intraepithelial neoplasia (CIN)], nonneoplastic abnormal (inflammation and human papilloma viral infection), and normal cervical tissues. A colposcope (low-magnification microscope used to view the cervix with reflected light) was used to identify 66 normal and 49 abnormal (5 inflammation, 21 human papilloma virus infection, and 23 CIN) sites on the cervix in 28 patients. These sites were then interrogated spectroscopically. A two-stage algorithm was developed to diagnose CIN. The first stage differentiated histologically abnormal tissues from colposcopically normal tissues with a sensitivity, specificity, and positive predictive value of 92%, 90%, and 88%, respectively. The second stage differentiated preneoplastic and neoplastic tissues from nonneoplastic abnormal tissues with a sensitivity, specificity, and positive predictive value of 87%, 73%, and 74%, respectively. Spectroscopic differences were consistent with a decrease in the absolute contribution of collagen fluorescence, an increase in the absolute contribution of oxyhemoglobin attenuation, and an increase in the relative contribution of reduced nicotinamide dinucleotide phosphate [NAD(P)H] fluorescence as tissue progresses from normal to abnormal in the same patient. These results suggest that in vivo fluorescence spectroscopy of the cervix can be used to diagnose CIN at colposcopy.

  7. Anti-cytokine autoantibodies are associated with opportunistic infection in patients with thymic neoplasia

    PubMed Central

    Burbelo, Peter D.; Sampaio, Elizabeth P.; Giaccone, Giuseppe; Zaman, Rifat; Kristosturyan, Ervand; Rajan, Arun; Ding, Li; Ching, Kathryn H.; Berman, Arlene; Oliveira, Joao B.; Hsu, Amy P.; Klimavicz, Caitlin M.; Iadarola, Michael J.; Holland, Steven M.

    2010-01-01

    Patients with thymic malignancy have high rates of autoimmunity leading to a variety of autoimmune diseases, most commonly myasthenia gravis caused by anti-acetylcholine receptor autoantibodies. High rates of autoantibodies to cytokines have also been described, although prevalence, spectrum, and functionality of these anti-cytokine autoantibodies are poorly defined. To better understand the presence and function of anti-cytokine autoantibodies, we created a luciferase immunoprecipitation system panel to search for autoantibodies against 39 different cytokines and examined plasma from controls (n = 30) and patients with thymic neoplasia (n = 17). In this screen, our patients showed statistically elevated, but highly heterogeneous immunoreactivity against 16 of the 39 cytokines. Some patients showed autoantibodies to multiple cytokines. Functional testing proved that autoantibodies directed against interferon-α, interferon-β, interleukin-1α (IL-1α), IL-12p35, IL-12p40, and IL-17A had biologic blocking activity in vitro. All patients with opportunistic infection showed multiple anti-cytokine autoantibodies (range 3-11), suggesting that anti-cytokine autoantibodies may be important in the pathogenesis of opportunistic infections in patients with thymic malignancy. This study was registered at http://clinicaltrials.gov as NCT00001355. PMID:20716769

  8. Expression of MMP-2, MMP-9, and urokinase-type plasminogen activator in cervical intraepithelial neoplasia.

    PubMed

    No, Jae Hong; Jo, Hoenil; Kim, Su-Hyeong; Park, In-Ae; Kang, Daehee; Lee, Chae Hyeong; Han, Seung-Su; Kim, Jae Weon; Park, Noh-Hyun; Kang, Soon-Beom; Song, Yong-Sang

    2009-08-01

    Matrix metalloproteinase-2 (MMP-2), MMP-9, and urokinase-type plasminogen activator (uPA) are important factors for cancer invasion and metastasis, degrading the extracellular matrix. They are also associated with angiogenesis. Angiogenic phenotype is another feature of high-grade cervical intraepithelial neoplasia (CIN). However, their associations with the progression of low-grade CIN to high-grade CIN are unexplored. We investigated whether these proteolytic enzyme expressions correlate with the progression of CIN. A total of 39 paraffin-embedded specimens from 10 patients with CIN grade 1, nine with CIN grade 2, and 20 with CIN grade 3 were assessed immunohistochemically by specific antibodies against MMP-2, MMP-9, and uPA. MMP-9 expression was higher in CIN 3 lesions (47.4%) than in CIN 1 (22.2%) and CIN 2 (20.2%) lesions, although the difference failed to reach statistical significance. The expression level of uPA and MMP-2 was not associated with the grade of CIN lesions. Interestingly, we found a significant association between expressions of uPA and MMP-2 (P= 0.028). Our results suggest that MMP-9 might play a role in the progression of CIN.

  9. [Multiple endocrine neoplasia type 1: genetic study of a large family].

    PubMed

    Orellana, C; Palasí, R; Martínez, F; Ponce, J L; Gil Sanz, J; Sancho Fornos, S; Prieto, F

    1999-03-01

    Multiple endocrine neoplasia syndrome type 1 (MEN-1) is an inherited disorder characterised by the predisposition of the cells from parathyroid glands, endocrine pancreas and adenohypophysis to develop neoplasms. We report the genetic study of an extended family with at least 8 affected patients and 10 putative carriers of a mutation in MEN-1 gene. One intragenic (Asp418 GAC-->GAT), and five flanking markers were characterised in the family by PCR amplification and polyachrylamide gel electrophoresis. Association of the disease to MEN-1 gene was confirmed for this family: all the affected members show a haplotype in common. Three patients at risk were diagnosed as non-carriers, since they have not inherited that haplotype. The remaining seven members, presymptomatic carriers, are included in a follow-up protocol. The genetic study of families segregating MEN-1 syndrome are useful in avoiding indiscriminate follow-up determinations to those members who have not received the genetic predisposition to develop any of the manifestations of the syndrome. Segregation analysis with linked markers is useful, under certain circumstances, to perform such type of studies. PMID:10207847

  10. Multiple oncogenic viruses identified in Ocular surface squamous neoplasia in HIV-1 patients

    PubMed Central

    2010-01-01

    Background Ocular surface squamous neoplasia (OSSN) is a rare cancer that has increased in incidence with the HIV pandemic in Africa. The underlying cause of this cancer in HIV-infected patients from Botswana is not well defined. Results Tissues were obtained from 28 OSSN and 8 pterygia patients. The tissues analyzed from OSSN patients were 83% positive for EBV, 75% were HPV positive, 70% were KSHV positive, 75% were HSV-1/2 positive, and 61% were CMV positive by PCR. Tissues from pterygium patients were 88% positive for EBV, 75% were HPV positive, 50% were KSHV positive, and 60% were CMV positive. None of the patients were JC or BK positive. In situ hybridization and immunohistochemistry analyses further identified HPV, EBV, and KSHV in a subset of the tissue samples. Conclusion We identified the known oncogenic viruses HPV, KSHV, and EBV in OSSN and pterygia tissues. The presence of these tumor viruses in OSSN suggests that they may contribute to the development of this malignancy in the HIV population. Further studies are necessary to characterize the molecular mechanisms associated with viral antigens and their potential role in the development of OSSN. PMID:20346104

  11. HPV-Based Screening, Triage, Treatment, and Followup Strategies in the Management of Cervical Intraepithelial Neoplasia

    PubMed Central

    Peralta-Zaragoza, Oscar; Deas, Jessica; Gómez-Cerón, Claudia; García-Suastegui, Wendy Argelia; Fierros-Zárate, Geny del Socorro; Jacobo-Herrera, Nadia Judith

    2013-01-01

    Cervical cancer is the second most common cause of death from cancer in women worldwide, and the development of new diagnostic, prognostic, and treatment strategies merits special attention. Many efforts have been made to design new drugs and develop immunotherapy and gene therapy strategies to treat cervical cancer. HPV genotyping has potentially valuable applications in triage of low-grade abnormal cervical cytology, assessment of prognosis and followup of cervical intraepithelial neoplasia, and in treatment strategies for invasive cervical cancer. It is known that during the development of cervical cancer associated with HPV infection, a cascade of abnormal events is induced, including disruption of cellular cycle control, alteration of gene expression, and deregulation of microRNA expression. Thus, the identification and subsequent functional evaluation of host proteins associated with HPV E6 and E7 oncoproteins may provide useful information in understanding cervical carcinogenesis, identifying cervical cancer molecular markers, and developing specific targeting strategies against tumor cells. Therefore, in this paper, we discuss the main diagnostic methods, management strategies, and followup of HPV-associated cervical lesions and review clinical trials applying gene therapy strategies against the development of cervical cancer. PMID:23690785

  12. [Histological evaluation of cryosurgery in high grade intraepithelial neoplasia (CIN-III)] of the uterine cervix].

    PubMed

    Rojas, I; Rodríguez, T; Pierotic, M; Le Cerf, P

    1993-01-01

    Sixty patients, having high grade cervical intraepithelial neoplasia (CIN III) are analyzed. They are all treated primarily with cryosurgery followed, approximately 12 weeks thereafter, by cervical conization, in order to histologically evaluate the response to treatment. The mean follow up of the whole series was 36 months. Ninetieth five percentage of the patients were included in the series, having an abnormal PAP smear, suggesting presence of a CIN. Colposcopically directed biopsy prior to cryosurgery showed grade CIN III, with no glandular involvement in 61.7% of the cases. In 38.3% the endocervical glands were involved, cryotherapy was done in 60 patients, with single freezing in 26 (43.3%) and double freezing in 34 (53.7%) patients. On analyzing the cone specimen, 71.7% of the cases showed no residual disease. The group that received double freezing did better than the single one (79 versus 61%). As well, the group with out gland involvement did better than the group showing such condition (83.8 versus 52.2%). Cryosurgery is a good therapeutic modality in cases with CIN III, following street selection criteria and having a good and reliable follow up.

  13. An update on vulvar intraepithelial neoplasia: terminology and a practical approach to diagnosis.

    PubMed

    Reyes, M Carolina; Cooper, Kumarasen

    2014-04-01

    There are two distinct types of vulvar intraepithelial neoplasia (VIN), which differ in their clinical presentation, aetiology, pathogenesis and histological/immunophenotypical features. One form driven by high-risk human papilloma virus infection usually occurs in young women and has been termed classic or usual VIN (uVIN). The other, not related to viral infection, occurs in postmenopausal women with chronic skin conditions such as lichen sclerosus and lichen simplex chronicus and is termed differentiated or simplex-type VIN. The latter is the precursor lesion of the most common type of squamous cell carcinoma (SCC) in the vulva, namely keratinizing SCC (representing 60% of cases). In contrast, uVIN usually gives rise to basaloid or warty SCC (40% of cases). The histological features of uVIN are similar to those of high grade lesions encountered in other lower anogenital tract sites (hyperchomatic nuclei with high nuclear to cytoplasmic ratios and increased mitotic activity). However, differentiated VIN has very subtle histopathological changes and often escapes diagnosis. Since uVIN is driven by high-risk human papilloma virus infections, p16 immunohistochemistry is diffusely positive in these lesions and is characterized with a high Ki-67 proliferation index. In contrast, differentiated or simplex-type VIN is consistently negative for p16 and the majority of the cases harbour TP53 mutations, correlating with p53 positivity by immunohistochemistry.

  14. Squamous vulvar intraepithelial neoplasia: 2004 modified terminology, ISSVD Vulvar Oncology Subcommittee.

    PubMed

    Sideri, Mario; Jones, Ronald W; Wilkinson, Edward J; Preti, Mario; Heller, Debra S; Scurry, James; Haefner, Hope; Neill, Sallie

    2005-11-01

    In the current classification, squamous vulvar intraepithelial neoplasia (VIN) is categorized as VIN 1, 2 and 3 according to the degree of abnormality. There is neither evidence that the VIN 1-3 morphologic spectrum reflects a biologic continuum nor that VIN 1 is a cancer precursor. The VIN 2 and 3 category includes 2 types of lesion, which differ in morphology, biology and clinical features. VIN, usual type (warty, basaloid and mixed), is HPV related in most cases. Invasive squamous carcinomas of warty or basaloid type is associated with VIN, usual type. VIN, differentiated type, is seen particularly in older women with lichen sclerosus and/or squamous cell hyperplasia in some cases. Neither VIN, differentiated type, nor associated keratinizing squamous cell carcinoma is HPV related. The term VIN should apply only to histologically high grade squamous lesions (former terms, VIN 2 and VIN 3 and differentiated VIN 3). The term VIN 1 will no longer be used. Two categories should describe squamous VIN: VIN, usual type (encompassing former VIN 2 and 3 of warty, basaloid and mixed types) and VIN, differentiated type (VIN 3, differentiated type).

  15. Evaluation of PpIX formation in Cervical Intraepithelial Neoplasia I (CIN) using widefield fluorescence images

    NASA Astrophysics Data System (ADS)

    Carbinatto, Fernanda M.; Inada, Natalia M.; Fortunato, Thereza C.; Lombardi, Welington; da Silva, Eduardo V.; Vollet Filho, José D.; Kurachi, Cristina; Pratavieira, Sebastião.; Bagnato, Vanderlei S.

    2016-03-01

    Optical techniques has been described as auxiliary technology for screening of neoplasia because shows the potential for tissues differentiation in real-time and it is a noninvasive detection and safe. However, only endogenous fluorophores presents the lesion may be insufficient and needed of the administration of the fluorophores synthesized, such as, precursor molecule of protoporphyrin IX (PpIX) induced by 5- aminolevulinic acid and your derivatives. Topical application of methylaminolevulinate (MAL), induces formation of the endogenous photosensitizer, PpIX in tissues where carcinogenesis has begun. The PpIX tend to accumulate in premalignant and malignant tissues and the illumination with light with appropriate wavelength beginning to excitation of PpIX fluorescence, which helps to localize PpIX-rich areas and identify potentially malignant tissues. The aim of the study is to evaluate the production of PpIX in the cervix with CIN I through of the fluorescence images captured after 1 hour of cream application. It was possible to visualize PpIX fluorescence in cervix and it was possible to observe the selectivity in fluorescence in squamous-columnar junction, which a pre-cancerous condition (CIN) and usually is localized. Through the image processing it was possible to quantify the increase of red fluorescence. For the CIN I the increase of red fluorescence was approximately of 4 times indicating a good PpIX formation.

  16. A retrospective study of the prevalence and classification of intestinal neoplasia in zebrafish (Danio rerio).

    PubMed

    Paquette, Colleen E; Kent, Michael L; Buchner, Cari; Tanguay, Robert L; Guillemin, Karen; Mason, Timothy J; Peterson, Tracy S

    2013-06-01

    For over a decade, spontaneous intestinal neoplasia has been observed in zebrafish (Danio rerio) submitted to the ZIRC (Zebrafish International Resource Center) diagnostic service. In addition, zebrafish displayed preneoplastic intestinal changes including hyperplasia, dysplasia, and enteritis. A total of 195 zebrafish, representing 2% of the total fish submitted to the service, were diagnosed with these lesions. Neoplastic changes were classified either as adenocarcinoma or small cell carcinoma, with a few exceptions (carcinoma not otherwise specified, tubular adenoma, and tubulovillous adenoma). Tumor prevalence appeared similarly distributed between sexes and generally occurred in zebrafish greater than 1 year of age, although neoplastic changes were observed in fish 6 months of age. Eleven lines displayed these preneoplastic and neoplastic changes, including wild-types and mutants. Affected zebrafish originated from 18 facilities, but the majority of fish were from a single zebrafish research facility (hereafter referred to as the primary facility) that has submitted numerous samples to the ZIRC diagnostic service. Zebrafish from the primary facility submitted as normal sentinel fish demonstrate that these lesions are most often subclinical. Fish fed the diet from the primary facility and held at another location did not develop intestinal lesions, indicating that diet is not the etiologic agent.

  17. Management of colorectal neoplasia during pregnancy and in the postpartum period

    PubMed Central

    Aytac, Erman; Ozuner, Gokhan; Isik, Ozgen; Gorgun, Emre; Stocchi, Luca

    2016-01-01

    AIM: To report our experience on management of colorectal neoplasia during pregnancy and in the postpartum period. METHODS: Patients who were diagnosed with colorectal cancer during pregnancy or in the postpartum period (< 6 mo), between 8/1997 and 4/2013, in our department were reviewed. Patient characteristics, operations, fetal health and follow-up during pregnancy, type of delivery and oncologic outcomes were analyzed. RESULTS: Eight patients met our study criteria. Median age at the time of diagnosis of colorectal cancer was 31 years. Median follow-up after surgery was 36 mo. Median duration of symptoms before diagnosis was 16 wk. Three patients were diagnosed with colorectal cancer during pregnancy and underwent surgery prior to delivery. None of the patients received adjuvant treatment during pregnancy. Five patients were diagnosed with colorectal cancer within a median of 2.1 mo after delivery and underwent surgery. No adverse neonatal outcomes were noted. All deliveries were at term (2 cesarean sections) except for one preterm delivery following low anterior resection on the 34th week of pregnancy. CONCLUSION: There has been a significant delay in the diagnosis of colorectal cancer which is probably due to overlap of symptoms and signs between these tumors and a normal pregnancy. Surgery for colorectal cancer during pregnancy can be performed safely without compromising maternal and fetal outcomes. PMID:27559434

  18. Metabonomic changes from pancreatic intraepithelial neoplasia to pancreatic ductal adenocarcinoma in tissues from rats.

    PubMed

    Wen, Shi; Li, Zhishui; Feng, Jianghua; Bai, Jianxi; Lin, Xianchao; Huang, Heguang

    2016-06-01

    Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant tumors and is difficult to diagnose in the early phase. This study was aimed at obtaining the metabolic profiles and characteristic metabolites of pancreatic intraepithelial neoplasia (PanIN) and PDAC tissues from Sprague-Dawley (SD) rats to establish metabonomic methods used in the early diagnosis of PDAC. In the present study, the animal models were established by embedding 7,12-dimethylbenzanthracene (DMBA) in the pancreas of SD rats to obtain PanIN and PDAC tissues. After the preprocessing of tissues, (1) H nuclear magnetic resonance (NMR) spectroscopy combined with multivariate and univariate statistical analysis was applied to identify the potential metabolic signatures and the corresponding metabolic pathways. Pattern recognition models were successfully established and differential metabolites, including glucose, amino acids, carboxylic acids and coenzymes, were screened out. Compared with the control, the trends in the variation of several metabolites were similar in both PanIN and PDAC. Kynurenate and methionine levels were elevated in PanIN but decreased in PDAC, thus, could served as biomarkers to distinguish PanIN from PDAC. Our results suggest that NMR-based techniques combined with multivariate statistical analysis can distinguish the metabolic differences among PanIN, PDAC and normal tissues, and, therefore, present a promising approach for physiopathologic metabolism investigations and early diagnoses of PDAC. PMID:27019331

  19. T-cell proliferative response to human papillomavirus type 16 peptides: relationship to cervical intraepithelial neoplasia.

    PubMed Central

    Nakagawa, M; Stites, D P; Farhat, S; Judd, A; Moscicki, A B; Canchola, A J; Hilton, J F; Palefsky, J M

    1996-01-01

    The incidence of human papillomavirus (HPV)-related cervical intraepithelial neoplasia (CIN) and cervical cancer is increased with immunodeficiency, but the role of immune response, including cell-mediated immunity, in disease prevention is not well understood. In this study, T-cell proliferative responses to six synthetic peptides with predicted immunogenic determinants from the HPV-16 E4, E6, E7, and L1 open reading frames were analyzed in 22 sexually active women with new-onset CIN and 65 sexually active women without cervical disease, characterized by cytology, colposcopy, and HPV testing. T-cell proliferative responses were demonstrated to all six HPV-16 peptides. Although not statistically significant, rates of reactivity to E6 (24-45) were higher among sexually active women without disease (26%) than among women with current CIN (7%), as was the overall number of peptides stimulating a response. Women with CIN may not respond to selected HPV antigens as well as women without disease do. PMID:8991637

  20. HIRA orchestrates a dynamic chromatin landscape in senescence and is required for suppression of neoplasia

    PubMed Central

    Cole, John J.; Nelson, David M.; Dikovskaya, Dina; Faller, William J.; Vizioli, Maria Grazia; Hewitt, Rachael N.; Anannya, Orchi; McBryan, Tony; Manoharan, Indrani; van Tuyn, John; Morrice, Nicholas; Pchelintsev, Nikolay A.; Ivanov, Andre; Brock, Claire; Drotar, Mark E.; Nixon, Colin; Clark, William; Sansom, Owen J.; Anderson, Kurt I.; King, Ayala; Blyth, Karen

    2014-01-01

    Cellular senescence is a stable proliferation arrest that suppresses tumorigenesis. Cellular senescence and associated tumor suppression depend on control of chromatin. Histone chaperone HIRA deposits variant histone H3.3 and histone H4 into chromatin in a DNA replication-independent manner. Appropriately for a DNA replication-independent chaperone, HIRA is involved in control of chromatin in nonproliferating senescent cells, although its role is poorly defined. Here, we show that nonproliferating senescent cells express and incorporate histone H3.3 and other canonical core histones into a dynamic chromatin landscape. Expression of canonical histones is linked to alternative mRNA splicing to eliminate signals that confer mRNA instability in nonproliferating cells. Deposition of newly synthesized histones H3.3 and H4 into chromatin of senescent cells depends on HIRA. HIRA and newly deposited H3.3 colocalize at promoters of expressed genes, partially redistributing between proliferating and senescent cells to parallel changes in expression. In senescent cells, but not proliferating cells, promoters of active genes are exceptionally enriched in H4K16ac, and HIRA is required for retention of H4K16ac. HIRA is also required for retention of H4K16ac in vivo and suppression of oncogene-induced neoplasia. These results show that HIRA controls a specialized, dynamic H4K16ac-decorated chromatin landscape in senescent cells and enforces tumor suppression. PMID:25512559

  1. Clinical significance of RET mutation screening in a pedigree of multiple endocrine neoplasia type 2A.

    PubMed

    Ying, Rongbiao; Feng, Jun

    2016-08-01

    The clinical characteristics and RET proto-oncogene (RET‑PO) mutation status of a patient with multiple endocrine neoplasia type 2A pedigree (MEN2A) was analyzed with the aim of preliminarily exploring the molecular mechanisms and clinical significance of the disease. Clinical characteristics of a single MEN2A patient were analyzed. Genomic DNA was extracted from the peripheral blood of the proband and 10 family members. The 21 exons of RET‑PO were PCR amplified and the amplified products were sequenced. Of the family members, 5 exhibited a C634Y (TGC→TAC) missense mutation in exon 11 of RET‑PO, among which 2 family members were screened as mutation carriers, while the others did not exhibit clinical symptoms of the mutation. The screening and analysis of RET‑PO mutations for the MEN2A proband and the family members suggests potential clinical phenotypes and enables assessment of the risk of disease development, thus providing useful information for determining the surgical timing of preventive thyroid gland removal. PMID:27277749

  2. The histologic features of intratubular germ cell neoplasia and its correlation with tumor behavior

    PubMed Central

    Basiri, Abbas; Movahhed, Saeed; Parvin, Mahmood; Salimi, Maziar

    2016-01-01

    Purpose To assess the prevalence of intratubular germ cell neoplasia (ITGCN) in patients with concurrent testis tumor and its correlation with histologic features and serum tumor markers. Materials and Methods From 2003 to 2015, 179 patients underwent radical orchiectomy due to testicular mass. Tissue specimens were evaluated by an expert uro-pathologist using immunohistochemistry (IHC) staining, in addition to light microscopy, to identify presence of ITGCN. Patients' demographic characteristics, histologic subtypes, pathologic stage of tumor and serum tumor markers were gathered and analyzed. Results Eighty-five out of 179 patients (47.5%) had concomitant ITGCN according to IHC staining. There was not statistically significant difference in histologic type, histologic components, cryptorchidism, and lymphovascular invasion between the 2 groups (p=0.151, p=0.11, p=0.233, p=0.413, and p=0.14, respectively). The prevalence of ITGCN was significantly higher in patients with stage T2 and T3 of tumor than those with stage T1. Elevated serum alpha feto protein level is much common in patients with ITGCN (p<0.001). Conclusions The prevalence of concurrent ITGCN in our region is lower than previous data from western countries. ITGCN is more common in higher tumor stages and is accompanied with elevated serum alpha feto protein levels before surgery. Presence of ITGCN in adjacent tissue may suggest a negative cancer behavior. PMID:27195317

  3. How significant is the association between metabolic syndrome and prevalence of colorectal neoplasia?

    PubMed Central

    Suchanek, Stepan; Grega, Tomas; Ngo, Ondrej; Vojtechova, Gabriela; Majek, Ondrej; Minarikova, Petra; Brogyuk, Nagyija; Bunganic, Bohus; Seifert, Bohumil; Dusek, Ladislav; Zavoral, Miroslav

    2016-01-01

    The incidence and prevalence of metabolic syndrome (MS) and colorectal cancer (CRC) has been rising in developed countries. The association between these two diseases has been widely studied and reported. Less evidence is available about the relationship between MS and CRC precancerous lesions (adenomatous polyps, adenomas). The aim of this paper is to present an overview of our scientific understanding of that topic and its implication in clinical practice. One of the principal goals of current CRC secondary prevention efforts is to detect and remove the precancerous lesions in individuals with an average CRC risk to prevent the development of invasive cancer. MS is not currently considered a high-risk CRC factor and is therefore not included in the guidelines of organized screening programs. However, in light of growing scientific evidence, the approach to patients with MS should be changed. Metabolic risk factors for the development of adenomas and cancers are the same - obesity, impaired glucose tolerance, dyslipidemia, hypertension, cardiovascular diseases and diabetes mellitus type 2. Therefore, the key issue in the near future is the development of a simple scoring system, easy to use in clinical practice, which would identify individuals with high metabolic risk of colorectal neoplasia and would be used for individual CRC secondary prevention strategies. Currently, such scoring systems have been published based on Asian (Asia-Pacific Colorectal Screening Score; APCS) and Polish populations. PMID:27688652

  4. Short interspersed CAN SINE elements as prognostic markers in canine mammary neoplasia.

    PubMed

    Gelaleti, Gabriela B; Granzotto, Adriana; Leonel, Camila; Jardim, Bruna V; Moschetta, Marina G; Carareto, Claudia M A; Zuccari, Debora Ap P C

    2014-01-01

    The genome of mammals is characterized by a large number of non-LTR retrotransposons, and among them, the CAN SINEs are characteristics of the canine species. Small amounts of DNA freely circulate in normal blood serum and high amounts are found in human patients with cancer, characterizing it as a candidate tumor-biomarker. The aim of this study was to estimate, through its absolute expression, the number of copies of CAN SINE sequences present in free circulating DNA of female dogs with mammary cancer, in order to correlate with the clinical and pathological characteristics and the follow-up period. The copy number of CAN SINE sequences was estimated by qPCR in 28 female dogs with mammary neoplasia. The univariate analysis showed an increased number of copies in female dogs with mammary tumor in female dogs >10 years old (p=0.02) and tumor time >18 months (p<0.05). The Kaplan-Meier test demonstrated a negative correlation between an increased number of copies and survival time (p=0.03). High amounts of CAN SINE fragments can be good markers for the detection of tumor DNA in blood and may characterize it as a marker of poor prognosis, being related to female dogs with shorter survival times. This estimate can be used as a prognostic marker in non-invasive breast cancer research and is useful in predicting tumor progression and patient monitoring. PMID:24173085

  5. Experimental pancreatic hyperplasia and neoplasia: effects of dietary and surgical manipulation.

    PubMed Central

    Watanapa, P.; Williamson, R. C.

    1993-01-01

    Several studies carried out during the past two decades have investigated the effect of dietary and surgical manipulation on pancreatic growth and carcinogenesis. Diets high in trypsin inhibitor stimulate pancreatic growth and increase the formation of preneoplastic lesions and carcinomas in the rat pancreas. Cholecystokinin (CCK) is the key intermediary in this response, since both natural and synthetic trypsin inhibitors increase circulating levels of the hormone and CCK antagonists largely prevent these changes. Fatty acids enhance pancreatic carcinogenesis in both rats and hamsters, whereas protein appears to have a protective role in the rat, but to increase tumour yields in the hamster. Several surgical operations affect the pancreas. Pancreatobiliary diversion and partial gastrectomy stimulate pancreatic growth and enhance carcinogenesis, probably by means of increased CCK release. Complete duodenogastric reflux has similar effects on the pancreas but the gut peptide involved is gastrin. Although massive small bowel resection increases pancreatic growth, the marked reduction in caloric absorption probably explains its failure to enhance carcinogenesis. CCK and enteroglucagon might work in concert to modulate the tropic response of the pancreas to small bowel resection. In the pancreas, as in the large intestine, hyperplasia appears to precede and predispose to neoplasia. PMID:8494719

  6. Is intraductal tubulopapillary neoplasia a new entity in the spectrum of familial pancreatic cancer syndrome?

    PubMed

    Del Chiaro, Marco; Mucelli, Raffaella Pozzi; Blomberg, John; Segersvärd, Ralf; Verbeke, Caroline

    2014-06-01

    We report on a 78-year old male with a positive family history for pancreatic cancer, who underwent total pancreatectomy for a suspected intraductal papillary mucinous neoplasm with extensive involvement of the main pancreatic duct and multiple branch ducts. The post operative course was uneventful. Macroscopic examination of the specimen revealed multiple solid non-mucinous tumour nodules throughout the main pancreatic duct and within multiple branch ducts. The microscopic appearance of the tumour, in particular its tubulopapillary growth pattern and immunohistochemical mucin profile (MUC1, MUC6 positive; MUC2, MUC5AC negative) were consistent with intraductal tubulopapillary neoplasia (ITPN) showing high-grade dysplasia. No evidence of stromal invasion was identified. To the best of our knowledge, this is the first report on ITPN in a high-risk patient based on a history of familial pancreatic cancer (FPC). The potential association between this entity and the spectrum of neoplastic lesions in FPC should be investigated with particular consideration of the lower biological aggressiveness of ITPN.

  7. c-Jun promotes whereas JunB inhibits epidermal neoplasia.

    PubMed

    Jin, Jane Y; Ke, Hengning; Hall, Russell P; Zhang, Jennifer Y

    2011-05-01

    Deregulation of the activator protein 1 (AP1) family gene regulators has been implicated in a wide range of diseases, including cancer. In this study we report that c-Jun was activated in human squamous cell carcinoma (SCC) and coexpression of c-Jun with oncogenic Ras was sufficient to transform primary human epidermal cells into malignancy in a regenerated human skin grafting model. In contrast, JunB was not induced in a majority of human SCC cells. Moreover, exogenous expression of JunB inhibited tumorigenesis driven by Ras or spontaneous human SCC cells. Conversely, the dominant-negative JunB mutant (DNJunB) promoted tumorigenesis, which is in contrast to the tumor-suppressor function of the corresponding c-Jun mutant. At the cellular level, JunB induced epidermal cell senescence and slowed cell growth in a cell-autonomous manner. Consistently, coexpression of JunB and Ras induced premature epidermal differentiation concomitant with upregulation of p16 and filaggrin and downregulation of cyclin D1 and cyclin-dependent kinase 4 (CDK4). These findings indicate that JunB and c-Jun differentially regulate cell growth and differentiation and induce opposite effects on epidermal neoplasia.JID JOURNAL CLUB ARTICLE: For questions, answers, and open discussion about this article, please go to http://www.nature.com/jid/journalclub.

  8. The food processing contaminant glyoxal promotes tumour growth in the multiple intestinal neoplasia (Min) mouse model.

    PubMed

    Svendsen, Camilla; Høie, Anja Hortemo; Alexander, Jan; Murkovic, Michael; Husøy, Trine

    2016-08-01

    Glyoxal is formed endogenously and at a higher rate in the case of hyperglycemia. Glyoxal is also a food processing contaminant and has been shown to be mutagenic and genotoxic in vitro. The tumourigenic potential of glyoxal was investigated using the multiple intestinal neoplasia (Min) mouse model, which spontaneously develops intestinal tumours and is susceptible to intestinal carcinogens. C57BL/6J females were mated with Min males. Four days after mating and throughout gestation and lactation, the pregnant dams were exposed to glyoxal through drinking water (0.0125%, 0.025%, 0.05%, 0.1%) or regular tap water. Female and male offspring were housed separately from PND21 and continued with the same treatment. One group were only exposed to 0.1% glyoxal from postnatal day (PND) 21. There was no difference in the number of intestinal tumours between control and treatment groups. However, exposure to 0.1% glyoxal starting in utero and at PND21 caused a significant increase in tumour size in the small intestine for male and female mice in comparison with respective control groups. This study suggests that glyoxal has tumour growth promoting properties in the small intestine in Min mice.

  9. c-Jun promotes whereas JunB inhibits epidermal neoplasia.

    PubMed

    Jin, Jane Y; Ke, Hengning; Hall, Russell P; Zhang, Jennifer Y

    2011-05-01

    Deregulation of the activator protein 1 (AP1) family gene regulators has been implicated in a wide range of diseases, including cancer. In this study we report that c-Jun was activated in human squamous cell carcinoma (SCC) and coexpression of c-Jun with oncogenic Ras was sufficient to transform primary human epidermal cells into malignancy in a regenerated human skin grafting model. In contrast, JunB was not induced in a majority of human SCC cells. Moreover, exogenous expression of JunB inhibited tumorigenesis driven by Ras or spontaneous human SCC cells. Conversely, the dominant-negative JunB mutant (DNJunB) promoted tumorigenesis, which is in contrast to the tumor-suppressor function of the corresponding c-Jun mutant. At the cellular level, JunB induced epidermal cell senescence and slowed cell growth in a cell-autonomous manner. Consistently, coexpression of JunB and Ras induced premature epidermal differentiation concomitant with upregulation of p16 and filaggrin and downregulation of cyclin D1 and cyclin-dependent kinase 4 (CDK4). These findings indicate that JunB and c-Jun differentially regulate cell growth and differentiation and induce opposite effects on epidermal neoplasia.JID JOURNAL CLUB ARTICLE: For questions, answers, and open discussion about this article, please go to http://www.nature.com/jid/journalclub. PMID:21289643

  10. Neoplasia and granulomas surrounding microchip transponders in Damaraland mole rats (Cryptomys damarensis).

    PubMed

    Sura, R; French, R A; Goldman, B D; Schwartz, D R

    2011-07-01

    Damaraland mole rats (Cryptomys damarensis) are among the longest-living rodents, with a maximum longevity of approximately 16 years. As one of the few mammals termed eusocial, these animals have been used in behavioral, genetic, metabolic, and physiologic research at the University of Connecticut since 1997. For individual identification at 3 to 4 months of age, mole rats were subcutaneously implanted with microchip transponders (11 mm in length) in the dorsal cervical region. In 2007, 2 of the 90 implanted adults, 10-year-old and 9-year-old females, developed subcutaneous masses at the site of the implant. Histopathological and immunohistochemical examinations revealed amelanotic melanoma and fibrosarcoma, respectively, with metastasis of the amelanotic melanoma. In 2008, a total of 3 adult males were castrated as part of a sex behavior study; 3 months later, all 3 castrated males developed subcutaneous masses around their implants, whereas none of the noncastrated males had masses. After an additional 9 months, these masses were found to be granulomas. To the authors' knowledge, this is the first report of neoplasia in this species. Both the tumors and the granulomas surrounded the microchip transponder.

  11. Scintigraphic portrayal of the syndrome of multiple endocrine neoplasia type-2B

    SciTech Connect

    Yobbagy, J.J.; Levatter, R.; Sisson, J.C.; Shulkin, B.L.; Polley, T.

    1988-06-01

    The scintigraphic appearance of the neoplasms in multiple endocrine neoplasia type 2B (MEN-2B) and the interpretations of the image patterns are described. An 18-year-old male patient with the MEN-2B syndrome underwent TI-201 imaging that showed concentrations of TI-201 in the primary medullary thyroid carcinoma (MTC) tumor and in cervical lymph node metastases. After total thyroidectomy and lymph node dissection, the TI-201 image was normal. Catecholamine levels in the blood and urine were only borderline elevated. Yet, greater than normal concentrations of I-131 metaiodobenzylguanidine (I-131 MIBG) were present in both adrenal glands. Computed tomography of the abdomen showed normal adrenal glands. These results were consistent with the diagnosis of adrenal medullary hyperplasia, a precursor of pheochromocytoma. No operation was indicated to remove the adrenal glands. Imaging with TI-201 appears to be useful in identifying sites of MTC in patients with the MEN-2B syndrome. I-131 MIBG imaging, in conjunction with computed tomography of the adrenal glands and appropriate catecholamine measurements, should be performed in patients with the MEN-2B syndrome to determine the status of the adrenal medullae, which then may be classified as normal, hyperplastic, or tumorous with pheochromocytoma.

  12. [Pituitary syndrome caused by neoplasia in a 17-month-old Holstein Friesian heifer].

    PubMed

    Wippermann, Wolf; Schöniger, Sandra; Gerlach, Kerstin; Schusser, Gerald Fritz; Köller, Gabor; Starke, Alexander

    2016-06-16

    A 17-month-old Holstein Friesian heifer was presented after one day with dysphagia, slight paralysis of the tongue and swelling of the eyelids. Clinical examination of the animal revealed an extended posture of the head and neck, severely increased salivation, reduced lingual tone and mandibular paralysis with complete absence of the swallowing reflex. The right eye showed a drooping eyelid, mucopurulent discharge, exposure keratitis, corneal opacity and miosis. On the left side, a moderate exophthalmos and slight mucous discharge from the nostril were observed. Neurological examination revealed the absence of multiple cranial nerve reflexes suggesting a pituitary syndrome. On X-rays, a soft-tissue opacity with sharp margins and a diameter of approximately 5 cm was seen. It was located ventral to the ethmoid bone with possible intraneurocranial origin. Rhinoscopically, a mass located distal to the ethmoid bone with an uneven, slightly reddish surface partly covered by purulent exudate was visualised. Post-mortem examination of the euthanized animal confirmed neoplasia, which ranged from the fossa hypophysialis of the corpus ossis basisphenoidalis to the ethmoid bone. Histopathologic findings matched a small, round, blue cell tumour. PMID:27172846

  13. Disseminated neoplasia causes changes in ploidy and apoptosis frequency in cockles Cerastoderma edule.

    PubMed

    Díaz, S; Villalba, A; Insua, A; Soudant, P; Fernández-Tajes, J; Méndez, J; Carballal, M J

    2013-07-01

    A proliferative disease, usually referred as disseminated neoplasia (DN), shows high prevalence in some cockle Cerastoderma edule beds of Galicia (NW Spain). Chromosome counts, examination of chromosome morphology, DNA quantification by flow cytometry and estimation of apoptosis frequency by TUNEL assay and flow cytometry were performed in cockles with different DN severity. Metaphases obtained from gills of DN-affected cockles displayed a chromosome number ranging from 41 to 145, while normal number is 38; changes in chromosome morphology were also evident, with numerous microchromosomes occurring. Haemolymph flow cytometry analysis revealed difference in DNA content between healthy and DN-affected cockles. Aneuploid peaks ranged from 1.3n to 8.9n. Apoptosis frequency was determined on histological sections (TUNEL assay) and haemolymph samples (flow cytometry). Both techniques revealed neoplastic cells in apoptosis. The higher DN severity, the lower the percentage of apoptotic cells. According to flow cytometry results, the negative association between DN severity and apoptosis frequency only affected the neoplastic cells, whereas DN did not significantly affect the percentage of apoptotic hyalinocytes or apoptotic granulocytes. PMID:23583807

  14. Cytomorphology and PCNA expression pattern in bivalves Mytilus galloprovincialis and Cerastoderma edule with haemic neoplasia.

    PubMed

    Carella, Francesca; Figueras, Antonio; Novoa, Beatriz; De Vico, Gionata

    2013-07-01

    Haemic neoplasia (HN) is a pathologic condition reported in several bivalve species in different geographic areas. In this study we describe the cytomorphological features and the proliferative behaviour, assessed by the proliferating cell nuclear antigen (PCNA), of HN in common cockle Cerastoderma edule and Mediterranean mussel Mytilus galloprovicialis. In mussels the presence of at least 5 types of atypical haemocytes was detected, including A- and B-type cells, previously described in M. edulis and Mytilus sp., with predominance of A-type cells in early phases of the disease and B-type cells in more advanced stages. PCNA immunostaining was positive for 97 to 100% of the neoplastic cells, with both cytoplasmic (A cells) and nuclear patterns (B cells). Conversely, in C. edule there was no distinctive morphological cell sub-population, and staining atypical haemocytes with PCNA (range 93 to 100%) showed nuclear expression in early phases of disease and cytoplasmic expression in more advanced stages. The above findings suggest distinct histo-pathogenetic pathways for HN in mussels and common cockles. PMID:23836773

  15. Thyroid dysfunction and neoplasia in children receiving neck irradiation for cancer

    SciTech Connect

    Fleming, I.D.; Black, T.L.; Thompson, E.I.; Pratt, C.; Rao, B.; Hustu, O.

    1985-03-15

    The reported relationship of radiation exposure and thyroid carcinoma stimulated this retrospective study of 298 patients treated at St. Jude Children's Hospital with radiation therapy to the neck for childhood cancer to identify patients who developed subsequent thyroid abnormalities. This series includes 153 patients with Hodgkin's disease, 95 with acute lymphocytic leukemia, 28 with lymphoepithelioma, and 22 with miscellaneous tumors. Inclusion in the study required 5 years of disease-free survival following therapy for their original tumor, which included thyroid irradiation. Follow-up has been 100%. Most patients also received chemotherapy. Seventeen patients were found to have decreased thyroid reserve with normal levels of free triiodothyroxine (T3) or free thyroxin, (T4) and an elevated level of thyroid-stimulating hormone (TSH). In nine patients hypothyroidism developed, with decreased T3 or T4 levels and an elevated level of TSH. One hyperthyroid patient was identified. Two patients had thyroiditis, and seven had thyroid neoplasms: (carcinoma in two, adenoma in two, colloid nodule in one, and undiagnosed nodules in two). This survey has demonstrated an increased incidence of thyroid dysfunction and thyroid neoplasia when compared to the general population. The importance of long-term follow-up for thyroid disease is emphasized in patients who have received thyroid irradiation. The possible role of subclinical hypothyroidism with TSH elevation coupled with radiation damage to the thyroid gland as a model for the development of neoplastic disease is discussed.

  16. Porcupine inhibitor suppresses paracrine Wnt-driven growth of Rnf43;Znrf3-mutant neoplasia

    PubMed Central

    Koo, Bon-Kyoung; van Es, Johan H.; van den Born, Maaike; Clevers, Hans

    2015-01-01

    Rnf43 (RING finger protein 43) and Znrf3 (zinc/RING finger protein 3) (RZ) are two closely related transmembrane E3 ligases, encoded by Wnt target genes, that remove surface Wnt (wingless-int) receptors. The two genes are mutated in various human cancers. Such tumors are predicted to be hypersensitive to, yet still depend on, secreted Wnts. We previously showed that mutation of RZ in the intestine yields rapidly growing adenomas containing LGR5+ (leucine-rich repeat-containing G-protein coupled receptor 5) stem cells and Wnt3-producing Paneth cells. We now show that removal of Paneth cells by Math1 mutation inhibits RZ−/− tumor formation. Similarly, deletion of Wnt3 inhibits tumorigenesis. Treatment of mice carrying RZ−/− intestinal neoplasia with a small molecule Wnt secretion inhibitor (porcupine inhibitor C59) strongly inhibited growth, whereas adjacent normal crypts remained intact. These results establish that paracrine Wnt secretion is an essential driver of RZ−/− tumor growth and imply that a therapeutic window exists for the use of porcupine inhibitors for RZ-mutant cancers. PMID:26023187

  17. Cutaneous lesion associated with multiple endocrine neoplasia type 2A: lichen amyloidosis or notalgia paresthetica?

    PubMed

    Chabre, O; Labat, F; Pinel, N; Berthod, F; Tarel, V; Bachelot, I

    1992-01-01

    Three patients of a French family demonstrated an association of multiple endocrine neoplasia type 2A (MEN 2A) with a pruritic scapular skin lesion. The lesions are similar to those described as familial cutaneous lichen amyloidosis in unrelated MEN 2A and medullary thyroid carcinoma families, but histological, immunohistochemical, and ultrastructural analysis of skin biopsies from each patient in the French family did not show amyloid deposition. The topography of the lesion follows dermatomes C8-D3. The patients report not only pruritus but also paresthesia and hyperalgesia, and one showed touch hypoesthesia and pain hyperesthesia in the area of the lesion. Such an association of cutaneous and neurological features suggests notalgia paresthetica (NP), a neuropathy of the posterior dorsal rami nerves. We thus suggest that the cutaneous lesions associated with MEN 2A might be secondary to pathology in the neural crest-derived dorsal sensory nerves. The amyloid, when present, would be secondary to scratching. We propose that patients presenting with familial NP be suspect for MEN 2A. PMID:1362414

  18. Fertility sparing surgery in gestational trophoblastic neoplasia: A report of 4 cases

    PubMed Central

    Hasanzadeh, Malihe; Vahid Roodsari, Ftemeh; Ahmadi, Shahnaz; Gavedan Mehr, Masoumeh; Azadeh, Tabari

    2016-01-01

    Background: Gestational trophoblastic neoplasia (GTN) is a curable disease that involves the development of malignant tumor in the woman after a normal or molar pregnancy. The position of surgery in GTN is not properly specified and is changing due to new chemotherapy protocols. However, the role of surgery is highlighted in chemotherapy-resistant GTN. Other indications of surgery in trophoblastic diseases are drug toxicity and uterine perforation. Based on the fact that most women in certain age tend to preserve fertility, this study reported 4 cases of successful treatment after fertility sparing surgery. Case: A hospital-based case-report study was carried out to investigate the role of surgery in 4 patients with GTN. In this study, acute complications, such as intra-abdominal bleeding and liver dysfunction due to chemotherapy occurred in some patients. Surgery was performed and all cases underwent localized tumor removal while preserving the uterus. No hysterectomy surgery was performed. Conclusion: Surgery is supposed in specific cases of GTN, who desire preserving fertility. PMID:27738663

  19. Radiogenic neoplasia in thyroid and mammary clonogens. Progress report, January 1, 1993--December 31, 1993

    SciTech Connect

    Clifton, K.H.

    1993-07-30

    The induction of cancer by ionizing radiation is a matter of great practical importance to the nuclear industry, to national defense, to radiological medicine and to the general public. It is increasingly apparent that carcinogenesis is one of the leading dose-limiting effects of radiation exposure (Co90). Quantitative information at the cellular level is essential to an understanding of the mechanisms of radiogenic neoplastic initiation and the stages of promotion and progression to overt neoplasia. We have developed two experimental models, the rat thyroid and rat mammary clonogen transplant systems, for the quantitative study of radiation carcinogenesis at the cellular level in vivo (C185). The most important steps taken or completed during the current grant year include: (a) demonstration of the high age-dependent radiosensitivity of prepubertal rat mammary clonogens to radiogenic damage which may influence their susceptibility to neoplastic initiation, and (b) demonstration of the feasibility of using a molecular test for clonogenicity in which Simple Sequence Repeats in the DNA serve as identifying signals of the genotypic origin of the cells. We have also (c) set up a large carcinogenesis experiment to test the effect of close intercellular contact in thyroid glands in situ on promotion-progression of radiogenically initiated clonogens, (d) achieved considerable further concentration of thyroid clonogens, and (e) begun to explore whether thyroid cells can be induced to give rise to three dimensional multicellular structures in culture in reconstituted basement membrane. These are discussed in this report.

  20. Soft shell clams Mya arenaria with disseminated neoplasia demonstrate reverse transcriptase activity

    USGS Publications Warehouse

    House, M.L.; Kim, C.H.; Reno, P.W.

    1998-01-01

    Disseminated neoplasia (DN), a proliferative cell disorder of the circulatory system of bivalves, was first reported in oysters in 1969. Since that time, the disease has been determined to be transmissible through water-borne exposure, but the etiological agent has not been unequivocally identified. In order to determine if a viral agent, possibly a retrovirus, could be the causative agent of DN, transmission experiments were performed, using both a cell-free filtrate and a sucrose gradient-purified preparation of a cell-free filtrate of DN positive materials. Additionally, a PCR-enhanced reverse transcriptase assay was used to determine if reverse transcriptase was present in tissues or hemolymph from DN positive soft shell clams Mya arenaria. DN was transmitted to healthy clams by injection with whole DN cells, but not with cell-free flitrates prepared from either tissues from DN positive clams, or DN cells. The cell-free preparations from DN-positive tissues and hemolymph having high levels of DN cells in circulation exhibited positive reactions in the PCR-enhanced reverse transcriptase assay. Cell-free preparations of hemolymph from clams having low levels of DN (<0.1% of cells abnormal), hemocytes from normal soft shell clams, and normal soft shell clam tissues did not produce a positive reaction in the PCR enhanced reverse transcriptase assay.

  1. Epithelial fusion during neural tube morphogenesis

    PubMed Central

    Pai, Yun-Jin; Abdullah, N.L.; Mohd.-Zin, S.W.; Mohammed, R. S.; Rolo, Ana; Greene, Nicholas D.E.; Abdul-Aziz, Noraishah M.; Copp, Andrew J.

    2013-01-01

    Adhesion and fusion of epithelial sheets marks the completion of many morphogenetic events during embryogenesis. Neural tube closure involves an epithelial fusion sequence in which the apposing neural folds adhere initially via cellular protrusions, proceed to a more stable union, and subsequently undergo remodelling of the epithelial structures to yield a separate neural tube roof plate and overlying non-neural ectoderm. Cellular protrusions comprise lamellipodia and filopodia, and studies in several different systems emphasise the critical role of RhoGTPases in their regulation. How epithelia establish initial adhesion is poorly understood but, in neurulation, may involve interactions between EphA receptors and their ephrinA ligands. Epithelial remodelling is spatially and temporally correlated with apoptosis in the dorsal neural tube midline, but experimental inhibition of this cell death does not prevent fusion and remodelling. A variety of molecular signalling systems have been implicated in the late events of morphogenesis, but genetic redundancy, for example among the integrins and laminins, makes identification of the critical players challenging. An improved understanding of epithelial fusion can provide insights into normal developmental processes, and may also indicate the mode of origin of clinically important birth defects. PMID:22945349

  2. Epithelial repair mechanisms in the lung

    PubMed Central

    Crosby, Lynn M.

    2010-01-01

    The recovery of an intact epithelium following lung injury is critical for restoration of lung homeostasis. The initial processes following injury include an acute inflammatory response, recruitment of immune cells, and epithelial cell spreading and migration upon an autologously secreted provisional matrix. Injury causes the release of factors that contribute to repair mechanisms including members of the epidermal growth factor and fibroblast growth factor families (TGF-α, KGF, HGF), chemokines (MCP-1), interleukins (IL-1β, IL-2, IL-4, IL-13), and prostaglandins (PGE2), for example. These factors coordinate processes involving integrins, matrix materials (fibronectin, collagen, laminin), matrix metalloproteinases (MMP-1, MMP-7, MMP-9), focal adhesions, and cytoskeletal structures to promote cell spreading and migration. Several key signaling pathways are important in regulating these processes, including sonic hedgehog, Rho GTPases, MAP kinase pathways, STAT3, and Wnt. Changes in mechanical forces may also affect these pathways. Both localized and distal progenitor stem cells are recruited into the injured area, and proliferation and phenotypic differentiation of these cells leads to recovery of epithelial function. Persistent injury may contribute to the pathology of diseases such as asthma, chronic obstructive pulmonary disease, and pulmonary fibrosis. For example, dysregulated repair processes involving TGF-β and epithelial-mesenchymal transition may lead to fibrosis. This review focuses on the processes of epithelial restitution, the localization and role of epithelial progenitor stem cells, the initiating factors involved in repair, and the signaling pathways involved in these processes. PMID:20363851

  3. Scattering attenuation microscopy of oral epithelial dysplasia

    NASA Astrophysics Data System (ADS)

    Tomlins, Pete H.; Adegun, Oluyori; Hagi-Pavli, Eleni; Piper, Kim; Bader, Dan; Fortune, Farida

    2010-11-01

    We present a new method for quantitative visualization of premalignant oral epithelium called scattering attenuation microscopy (SAM). Using low-coherence interferometry, SAM projects measurements of epithelial optical attenuation onto an image of the tissue surface as a color map. The measured attenuation is dominated by optical scattering that provides a metric of the severity of oral epithelial dysplasia (OED). Scattering is sensitive to the changes in size and distribution of nuclear material that are characteristic of OED, a condition recognized by the occurrence of basal-cell-like features throughout the epithelial depth. SAM measures the axial intensity change of light backscattered from epithelial tissue. Scattering measurements are obtained from sequential axial scans of a 3-D tissue volume and displayed as a 2-D SAM image. A novel segmentation method is used to confine scattering measurement to epithelial tissue. This is applied to oral biopsy samples obtained from 19 patients. Our results show that imaging of tissue scattering can be used to discriminate between different dysplastic severities and furthermore presents a powerful tool for identifying the most representative tissue site for biopsy.

  4. Mortality by neoplasia and cellular telephone base stations in the Belo Horizonte municipality, Minas Gerais state, Brazil.

    PubMed

    Dode, Adilza C; Leão, Mônica M D; Tejo, Francisco de A F; Gomes, Antônio C R; Dode, Daiana C; Dode, Michael C; Moreira, Cristina W; Condessa, Vânia A; Albinatti, Cláudia; Caiaffa, Waleska T

    2011-09-01

    Pollution caused by the electromagnetic fields (EMFs) of radio frequencies (RF) generated by the telecommunication system is one of the greatest environmental problems of the twentieth century. The purpose of this research was to verify the existence of a spatial correlation between base station (BS) clusters and cases of deaths by neoplasia in the Belo Horizonte municipality, Minas Gerais state, Brazil, from 1996 to 2006 and to measure the human exposure levels to EMF where there is a major concentration of cellular telephone transmitter antennas. A descriptive spatial analysis of the BSs and the cases of death by neoplasia identified in the municipality was performed through an ecological-epidemiological approach, using georeferencing. The database employed in the survey was composed of three data banks: 1. death by neoplasia documented by the Health Municipal Department; 2. BSs documented in ANATEL ("Agência Nacional de Telecomunicações": 'Telecommunications National Agency'); and 3. census and demographic city population data obtained from official archives provided by IBGE ("Instituto Brasileiro de Geografia e Estatística": 'Brazilian Institute of Geography and Statistics'). The results show that approximately 856 BSs were installed through December 2006. Most (39.60%) of the BSs were located in the "Centro-Sul" ('Central-Southern') region of the municipality. Between 1996 and 2006, 7191 deaths by neoplasia occurred and within an area of 500 m from the BS, the mortality rate was 34.76 per 10,000 inhabitants. Outside of this area, a decrease in the number of deaths by neoplasia occurred. The greatest accumulated incidence was 5.83 per 1000 in the Central-Southern region and the lowest incidence was 2.05 per 1000 in the Barreiro region. During the environmental monitoring, the largest accumulated electric field measured was 12.4 V/m and the smallest was 0.4 V/m. The largest density power was 40.78 μW/cm(2), and the smallest was 0.04 μW/cm(2).

  5. Human glomerular epithelial cell proteoglycans

    SciTech Connect

    Thomas, G.J.; Jenner, L.; Mason, R.M.; Davies, M. )

    1990-04-01

    Proteoglycans synthesized by cultures of human glomerular epithelial cells have been isolated and characterized. Three types of heparan sulfate were detected. Heparan sulfate proteoglycan I (HSPG-I; Kav 6B 0.04) was found in the cell layer and medium and accounted for 12% of the total proteoglycans synthesized. HSPG-II (Kav 6B 0.25) accounted for 18% of the proteoglycans and was located in the medium and cell layer. A third population (9% of the proteoglycan population), heparan sulfate glycosaminoglycan (HS-GAG; Kav 6B 0.4-0.8), had properties consistent with single glycosaminoglycan chains or their fragments and was found only in the cell layer. HSPG-I and HSPG-II from the cell layer had hydrophobic properties; they were released from the cell layer by mild trypsin treatment. HS-GAG lacked these properties, consisted of low-molecular-mass heparan sulfate oligosaccharides, and were intracellular. HSPG-I and -II released to the medium lacked hydrophobic properties. The cells also produced three distinct types of chondroitin sulfates. The major species, chondroitin sulfate proteoglycan I (CSPG-I) eluted in the excluded volume of a Sepharose CL-6B column, accounted for 30% of the proteoglycans detected, and was found in both the cell layer and medium. Cell layer CSPG-I bound to octyl-Sepharose. It was released from the cell layer by mild trypsin treatment. CSPG-II (Kav 6B 0.1-0.23) accounted for 10% of the total 35S-labeled macromolecules and was found predominantly in the culture medium. A small amount of CS-GAG (Kav 6B 0.25-0.6) is present in the cell extract and like HS-GAG is intracellular. Pulse-chase experiments indicated that HSPG-I and -II and CSPG-I and -II are lost from the cell layer either by direct release into the medium or by internalization where they are metabolized to single glycosaminoglycan chains and subsequently to inorganic sulfate.

  6. Risk of Advanced Neoplasia in First-Degree Relatives with Colorectal Cancer: A Large Multicenter Cross-Sectional Study

    PubMed Central

    Quintero, Enrique; Gargallo, Carla; Lanas, Angel; Bujanda, Luis; Gimeno-García, Antonio Z.; Hernández-Guerra, Manuel; Nicolás-Pérez, David; Alonso-Abreu, Inmaculada; Morillas, Juan Diego; Balaguer, Francesc; Muriel, Alfonso

    2016-01-01

    Background First-degree relatives (FDR) of patients with colorectal cancer have a higher risk of developing colorectal cancer than the general population. For this reason, screening guidelines recommend colonoscopy every 5 or 10 y, starting at the age of 40, depending on whether colorectal cancer in the index-case is diagnosed at <60 or ≥60 y, respectively. However, studies on the risk of neoplastic lesions are inconclusive. The aim of this study was to determine the risk of advanced neoplasia (three or more non-advanced adenomas, advanced adenoma, or invasive cancer) in FDR of patients with colorectal cancer compared to average-risk individuals (i.e., asymptomatic adults 50 to 69 y of age with no family history of colorectal cancer). Methods and Findings This cross-sectional analysis includes data from 8,498 individuals undergoing their first lifetime screening colonoscopy between 2006 and 2012 at six Spanish tertiary hospitals. Of these individuals, 3,015 were defined as asymptomatic FDR of patients with colorectal cancer (“familial-risk group”) and 3,038 as asymptomatic with average-risk for colorectal cancer (“average-risk group”). The familial-risk group was stratified as one FDR, with one family member diagnosed with colorectal cancer at ≥60 y (n = 1,884) or at <60 y (n = 831), and as two FDR, with two family members diagnosed with colorectal cancer at any age (n = 300). Multiple logistic regression analysis was used for between-group comparisons after adjusting for potential confounders (age, gender, and center). Compared with the average-risk group, advanced neoplasia was significantly more prevalent in individuals having two FDR with colorectal cancer (odds ratio [OR] 1.90; 95% confidence interval [CI] 1.36–2.66, p < 0.001), but not in those having one FDR with colorectal cancer diagnosed at ≥60 y (OR 1.03; 95% CI 0.83–1.27, p = 0.77) and <60 y (OR 1.19; 95% CI 0.90–1.58, p = 0.20). After the age of 50 y, men developed advanced

  7. Adipose and mammary epithelial tissue engineering.

    PubMed

    Zhu, Wenting; Nelson, Celeste M

    2013-01-01

    Breast reconstruction is a type of surgery for women who have had a mastectomy, and involves using autologous tissue or prosthetic material to construct a natural-looking breast. Adipose tissue is the major contributor to the volume of the breast, whereas epithelial cells comprise the functional unit of the mammary gland. Adipose-derived stem cells (ASCs) can differentiate into both adipocytes and epithelial cells and can be acquired from autologous sources. ASCs are therefore an attractive candidate for clinical applications to repair or regenerate the breast. Here we review the current state of adipose tissue engineering methods, including the biomaterials used for adipose tissue engineering and the application of these techniques for mammary epithelial tissue engineering. Adipose tissue engineering combined with microfabrication approaches to engineer the epithelium represents a promising avenue to replicate the native structure of the breast.

  8. Epithelial-Mesenchymal Transition and Breast Cancer

    PubMed Central

    Wu, Yanyuan; Sarkissyan, Marianna; Vadgama, Jaydutt V.

    2016-01-01

    Breast cancer is the most common cancer in women and distant site metastasis is the main cause of death in breast cancer patients. There is increasing evidence supporting the role of epithelial-mesenchymal transition (EMT) in tumor cell progression, invasion, and metastasis. During the process of EMT, epithelial cancer cells acquire molecular alternations that facilitate the loss of epithelial features and gain of mesenchymal phenotype. Such transformation promotes cancer cell migration and invasion. Moreover, emerging evidence suggests that EMT is associated with the increased enrichment of cancer stem-like cells (CSCs) and these CSCs display mesenchymal characteristics that are resistant to chemotherapy and target therapy. However, the clinical relevance of EMT in human cancer is still under debate. This review will provide an overview of current evidence of EMT from studies using clinical human breast cancer tissues and its associated challenges. PMID:26821054

  9. Gap geometry dictates epithelial closure efficiency

    PubMed Central

    Ravasio, Andrea; Cheddadi, Ibrahim; Chen, Tianchi; Pereira, Telmo; Ong, Hui Ting; Bertocchi, Cristina; Brugues, Agusti; Jacinto, Antonio; Kabla, Alexandre J.; Toyama, Yusuke; Trepat, Xavier; Gov, Nir; Neves de Almeida, Luís; Ladoux, Benoit

    2015-01-01

    Closure of wounds and gaps in tissues is fundamental for the correct development and physiology of multicellular organisms and, when misregulated, may lead to inflammation and tumorigenesis. To re-establish tissue integrity, epithelial cells exhibit coordinated motion into the void by active crawling on the substrate and by constricting a supracellular actomyosin cable. Coexistence of these two mechanisms strongly depends on the environment. However, the nature of their coupling remains elusive because of the complexity of the overall process. Here we demonstrate that epithelial gap geometry in both in vitro and in vivo regulates these collective mechanisms. In addition, the mechanical coupling between actomyosin cable contraction and cell crawling acts as a large-scale regulator to control the dynamics of gap closure. Finally, our computational modelling clarifies the respective roles of the two mechanisms during this process, providing a robust and universal mechanism to explain how epithelial tissues restore their integrity. PMID:26158873

  10. Gap geometry dictates epithelial closure efficiency.

    PubMed

    Ravasio, Andrea; Cheddadi, Ibrahim; Chen, Tianchi; Pereira, Telmo; Ong, Hui Ting; Bertocchi, Cristina; Brugues, Agusti; Jacinto, Antonio; Kabla, Alexandre J; Toyama, Yusuke; Trepat, Xavier; Gov, Nir; Neves de Almeida, Luís; Ladoux, Benoit

    2015-07-09

    Closure of wounds and gaps in tissues is fundamental for the correct development and physiology of multicellular organisms and, when misregulated, may lead to inflammation and tumorigenesis. To re-establish tissue integrity, epithelial cells exhibit coordinated motion into the void by active crawling on the substrate and by constricting a supracellular actomyosin cable. Coexistence of these two mechanisms strongly depends on the environment. However, the nature of their coupling remains elusive because of the complexity of the overall process. Here we demonstrate that epithelial gap geometry in both in vitro and in vivo regulates these collective mechanisms. In addition, the mechanical coupling between actomyosin cable contraction and cell crawling acts as a large-scale regulator to control the dynamics of gap closure. Finally, our computational modelling clarifies the respective roles of the two mechanisms during this process, providing a robust and universal mechanism to explain how epithelial tissues restore their integrity.

  11. Adipose and mammary epithelial tissue engineering

    PubMed Central

    Zhu, Wenting; Nelson, Celeste M.

    2013-01-01

    Breast reconstruction is a type of surgery for women who have had a mastectomy, and involves using autologous tissue or prosthetic material to construct a natural-looking breast. Adipose tissue is the major contributor to the volume of the breast, whereas epithelial cells comprise the functional unit of the mammary gland. Adipose-derived stem cells (ASCs) can differentiate into both adipocytes and epithelial cells and can be acquired from autologous sources. ASCs are therefore an attractive candidate for clinical applications to repair or regenerate the breast. Here we review the current state of adipose tissue engineering methods, including the biomaterials used for adipose tissue engineering and the application of these techniques for mammary epithelial tissue engineering. Adipose tissue engineering combined with microfabrication approaches to engineer the epithelium represents a promising avenue to replicate the native structure of the breast. PMID:23628872

  12. Biomarkers for epithelial-mesenchymal transitions

    PubMed Central

    Zeisberg, Michael; Neilson, Eric G.

    2009-01-01

    Somatic cells that change from one mature phenotype to another exhibit the property of plasticity. It is increasingly clear that epithelial and endothelial cells enjoy some of this plasticity, which is easily demonstrated by studying the process of epithelial-mesenchymal transition (EMT). Published reports from the literature typically rely on ad hoc criteria for determining EMT events; consequently, there is some uncertainty as to whether the same process occurs under different experimental conditions. As we discuss in this Personal Perspective, we believe that context and various changes in plasticity biomarkers can help identify at least three types of EMT and that using a collection of criteria for EMT increases the likelihood that everyone is studying the same phenomenon — namely, the transition of epithelial and endothelial cells to a motile phenotype. PMID:19487819

  13. Epithelial Intermediate Filaments: Guardians against Microbial Infection?

    PubMed Central

    Geisler, Florian; Leube, Rudolf E.

    2016-01-01

    Intermediate filaments are abundant cytoskeletal components of epithelial tissues. They have been implicated in overall stress protection. A hitherto poorly investigated area of research is the function of intermediate filaments as a barrier to microbial infection. This review summarizes the accumulating knowledge about this interaction. It first emphasizes the unique spatial organization of the keratin intermediate filament cytoskeleton in different epithelial tissues to protect the organism against microbial insults. We then present examples of direct interaction between viral, bacterial, and parasitic proteins and the intermediate filament system and describe how this affects the microbe-host interaction by modulating the epithelial cytoskeleton, the progression of infection, and host response. These observations not only provide novel insights into the dynamics and function of intermediate filaments but also indicate future avenues to combat microbial infection. PMID:27355965

  14. Epithelial-mesenchymal transition can suppress major attributes of human epithelial tumor-initiating cells

    PubMed Central

    Celià-Terrassa, Toni; Meca-Cortés, Óscar; Mateo, Francesca; Martínez de Paz, Alexia; Rubio, Nuria; Arnal-Estapé, Anna; Ell, Brian J.; Bermudo, Raquel; Díaz, Alba; Guerra-Rebollo, Marta; Lozano, Juan José; Estarás, Conchi; Ulloa, Catalina; ρlvarez-Simón, Daniel; Milà, Jordi; Vilella, Ramón; Paciucci, Rosanna; Martínez-Balbás, Marian; García de Herreros, Antonio; Gomis, Roger R.; Kang, Yibin; Blanco, Jerónimo; Fernández, Pedro L.; Thomson, Timothy M.

    2012-01-01

    Malignant progression in cancer requires populations of tumor-initiating cells (TICs) endowed with unlimited self renewal, survival under stress, and establishment of distant metastases. Additionally, the acquisition of invasive properties driven by epithelial-mesenchymal transition (EMT) is critical for the evolution of neoplastic cells into fully metastatic populations. Here, we characterize 2 human cellular models derived from prostate and bladder cancer cell lines to better understand the relationship between TIC and EMT programs in local invasiveness and distant metastasis. The model tumor subpopulations that expressed a strong epithelial gene program were enriched in highly metastatic TICs, while a second subpopulation with stable mesenchymal traits was impoverished in TICs. Constitutive overexpression of the transcription factor Snai1 in the epithelial/TIC-enriched populations engaged a mesenchymal gene program and suppressed their self renewal and metastatic phenotypes. Conversely, knockdown of EMT factors in the mesenchymal-like prostate cancer cell subpopulation caused a gain in epithelial features and properties of TICs. Both tumor cell subpopulations cooperated so that the nonmetastatic mesenchymal-like prostate cancer subpopulation enhanced the in vitro invasiveness of the metastatic epithelial subpopulation and, in vivo, promoted the escape of the latter from primary implantation sites and accelerated their metastatic colonization. Our models provide new insights into how dynamic interactions among epithelial, self-renewal, and mesenchymal gene programs determine the plasticity of epithelial TICs. PMID:22505459

  15. Mesenchymal-epithelial interactions during digestive tract development and epithelial stem cell regeneration.

    PubMed

    Le Guen, Ludovic; Marchal, Stéphane; Faure, Sandrine; de Santa Barbara, Pascal

    2015-10-01

    The gastrointestinal tract develops from a simple and uniform tube into a complex organ with specific differentiation patterns along the anterior-posterior and dorso-ventral axes of asymmetry. It is derived from all three germ layers and their cross-talk is important for the regulated development of fetal and adult gastrointestinal structures and organs. Signals from the adjacent mesoderm are essential for the morphogenesis of the overlying epithelium. These mesenchymal-epithelial interactions govern the development and regionalization of the different gastrointestinal epithelia and involve most of the key morphogens and signaling pathways, such as the Hedgehog, BMPs, Notch, WNT, HOX, SOX and FOXF cascades. Moreover, the mechanisms underlying mesenchyme differentiation into smooth muscle cells influence the regionalization of the gastrointestinal epithelium through interactions with the enteric nervous system. In the neonatal and adult gastrointestinal tract, mesenchymal-epithelial interactions are essential for the maintenance of the epithelial regionalization and digestive epithelial homeostasis. Disruption of these interactions is also associated with bowel dysfunction potentially leading to epithelial tumor development. In this review, we will discuss various aspects of the mesenchymal-epithelial interactions observed during digestive epithelium development and differentiation and also during epithelial stem cell regeneration. PMID:26126787

  16. Physiology of Epithelial Chloride and Fluid Secretion

    PubMed Central

    Frizzell, Raymond A.; Hanrahan, John W.

    2012-01-01

    Epithelial salt and water secretion serves a variety of functions in different organ systems, such as the airways, intestines, pancreas, and salivary glands. In cystic fibrosis (CF), the volume and/or composition of secreted luminal fluids are compromised owing to mutations in the gene encoding CFTR, the apical membrane anion channel that is responsible for salt secretion in response to cAMP/PKA stimulation. This article examines CFTR and related cellular transport processes that underlie epithelial anion and fluid secretion, their regulation, and how these processes are altered in CF disease to account for organ-specific secretory phenotypes. PMID:22675668

  17. Extensive Focal Epithelial Hyperplasia: A Case Report.

    PubMed

    Mansouri, Zahra; Bakhtiari, Sedigheh; Noormohamadi, Robab

    2015-01-01

    Focal epithelial hyperplasia (FEH) or Heck's disease is a rare viral infection of the oral mucosa caused by human papilloma virus especially subtypes 13 or 32. The frequency of this disease varies widely from one geographic region and ethnic groups to another. This paper reports an Iranian case of extensive focal epithelial hyperplasia. A 35-year-old man with FEH is described, in whom the lesions had persisted for more than 25 years. The lesion was diagnosed according to both clinical and histopathological features. Dental practitioner should be aware of these types of lesions and histopathological examination together and a careful clinical observation should be carried out for a definitive diagnosis.

  18. The combined epithelial odontogenic tumour in Malaysians.

    PubMed

    Siar, C H; Ng, K H

    1991-04-01

    The combined epithelial odontogenic tumour represents a hybrid lesion comprising primarily areas of adenomatoid odontogenic tumour intermixed with foci of calcifying epithelial odontogenic tumour. Five such cases retrieved from the files of the Division of Stomatology, Institute for Medical Research, Kuala Lumpur, and four others from the existing literature were analysed. A mean age of 18.8 years, a female preponderance (66.7%) with a male to female ratio of 1:2 and predilection for the mandible (55.6%) were observed. All cases were treated by conservative surgery and the lack of recurrence confirmed the innocuous nature of this lesion.

  19. Respiratory epithelial cells orchestrate pulmonary innate immunity

    PubMed Central

    Whitsett, Jeffrey A; Alenghat, Theresa

    2015-01-01

    The epithelial surfaces of the lungs are in direct contact with the environment and are subjected to dynamic physical forces as airway tubes and alveoli are stretched and compressed during ventilation. Mucociliary clearance in conducting airways, reduction of surface tension in the alveoli, and maintenance of near sterility have been accommodated by the evolution of a multi-tiered innate host-defense system. The biophysical nature of pulmonary host defenses are integrated with the ability of respiratory epithelial cells to respond to and ‘instruct’ the professional immune system to protect the lungs from infection and injury. PMID:25521682

  20. The Crosstalk between Nrf2 and TGF-β1 in the Epithelial-Mesenchymal Transition of Pancreatic Duct Epithelial Cells.

    PubMed

    Arfmann-Knübel, Sarah; Struck, Birte; Genrich, Geeske; Helm, Ole; Sipos, Bence; Sebens, Susanne; Schäfer, Heiner

    2015-01-01

    Nrf2 and TGF-β1 both affect tumorigenesis in a dual fashion, either by preventing carcinogen induced carcinogenesis and suppressing tumor growth, respectively, or by conferring cytoprotection and invasiveness to tumor cells during malignant transformation. Given the involvement of Nrf2 and TGF-β1 in the adaptation of epithelial cells to persistent inflammatory stress, e.g. of the pancreatic duct epithelium during chronic pancreatitis, a crosstalk between Nrf2 and TGF-β1 can be envisaged. By using premalignant human pancreatic duct cells (HPDE) and the pancreatic ductal adenocarcinoma cell line Colo357, we could show that Nrf2 and TGF-β1 independently but additively conferred an invasive phenotype to HPDE cells, whereas acting synergistically in Colo357 cells. This was accompanied by differential regulation of EMT markers like vimentin, Slug, L1CAM and E-cadherin. Nrf2 activation suppressed E-cadherin expression through an as yet unidentified ARE related site in the E-cadherin promoter, attenuated TGF-β1 induced Smad2/3-activity and enhanced JNK-signaling. In Colo357 cells, TGF-β1 itself was capable of inducing Nrf2 whereas in HPDE cells TGF-β1 per-se did not affect Nrf2 activity, but enhanced Nrf2 induction by tBHQ. In Colo357, but not in HPDE cells, the effects of TGF-β1 on invasion were sensitive to Nrf2 knock-down. In both cell lines, E-cadherin re-expression inhibited the proinvasive effect of Nrf2. Thus, the increased invasion of both cell lines relates to the Nrf2-dependent downregulation of E-cadherin expression. In line, immunohistochemistry analysis of human pancreatic intraepithelial neoplasias in pancreatic tissues from chronic pancreatitis patients revealed strong Nrf2 activity already in premalignant epithelial duct cells, accompanied by partial loss of E-cadherin expression. Our findings indicate that Nrf2 and TGF-β1 both contribute to malignant transformation through distinct EMT related mechanisms accounting for an invasive phenotype

  1. Detection of the alpha-subunit of inhibin in trophoblastic neoplasia.

    PubMed

    Pelkey, T J; Frierson, H F; Mills, S E; Stoler, M H

    1999-01-01

    Placental trophoblasts are the primary source of serum inhibin during pregnancy. We sought to characterize inhibin immunolabeling in trophoblastic neoplasms and compare the results with those for established markers of trophoblastic differentiation. Formalin-fixed, paraffin-embedded tissues from three normal term placentas, 13 hydatidiform moles (HM), five choriocarcinomas (CC) (three gestational, one testicular, one mediastinal), and five placental site trophoblastic tumors (PSTT) were immunolabeled with antibodies to the alpha-subunit of inhibin, hPL, and beta-hCG. Additionally, six first-trimester placentas were immunolabeled with antibody to inhibin alone. Trophoblastic subpopulations were assessed for the number of positive cells (1% to 24% = 1+,25% to 49% = 2+,50% to 74% = 3+, 75% to 100% = 4+). Immunolabeling in term placenta and HM was similar, because beta-hCG was the most sensitive marker (4+) of syncytiotrophoblasts followed by inhibin (3-4+) and hPL (2-3+). Immunolabeling of syncytiotrophoblasts in CC was similar to that in term placenta and HM, except for negative hPL staining in two cases. In HM, inhibin labeling of intermediate trophoblasts (2-3+) was less than that for hPL (3-4+). In CC, inhibin and hPL labeling of intermediate trophoblasts was more variable with negative hPL reactivity in two cases. Inhibin and hPL did not stain cytotrophoblasts. In PSTT, inhibin immunolabeling was a better marker than hPL in two cases, inferior in two, and similar in one. Inhibin labeling of syncytiotrophoblasts was less than that for beta-hCG, but did not have the often marked background staining that was present with beta-hCG. Immunolabeling of trophoblast subpopulations for inhibin was similar between first-trimester placenta, term placenta, and HM. We conclude that inhibin is a useful immunohistochemical marker of trophoblastic neoplasia and should be included in the antibody panel with beta-hCG and hPL.

  2. Von Hippel-Lindau Disease: Genetics and Role of Genetic Counseling in a Multiple Neoplasia Syndrome.

    PubMed

    Nielsen, Sarah M; Rhodes, Lindsay; Blanco, Ignacio; Chung, Wendy K; Eng, Charis; Maher, Eamonn R; Richard, Stéphane; Giles, Rachel H

    2016-06-20

    Von Hippel-Lindau disease (VHL) is one of the most common inherited neoplasia syndromes and is characterized by highly vascular tumors of the eyes, brain, and spine, as well as benign and malignant tumors and/or cysts of the kidneys, adrenal medullae and sympathetic paraganglia, endolymphatic sac, epididymis, and broad ligament. Since the discovery of the VHL gene in 1993, more than 900 families with VHL have been identified and examined. Genetic testing for VHL is widely available and will detect a disease-causing mutation in rate 95% to 100% of individuals who have a clinical diagnosis of VHL, making it the standard of care for diagnosis of VHL. Furthermore, genetic testing for VHL is indicated in some individuals with seemingly sporadic VHL-related tumor types, as ≤ 10% of pheochromocytoma or early-onset renal cell carcinoma and ≤ 40% of CNS hemangioblastoma harbor germline VHL mutations without a family history or additional features of VHL disease. The majority of VHL mutations are private, but there are also well-characterized founder mutations. VHL is a complex, multiorgan disease that spans the breadth of oncology subspecialties, and, as such, providers in these subspecialties should be aware of when to consider a diagnosis of VHL, when to refer a patient to a genetics specialist for consideration of gene testing, and, perhaps most importantly, how to communicate this sensitive information in an age-appropriate manner to at-risk families. This review will provide state-of-the-art information regarding the genetics of VHL and will serve as a key reference for nongenetics professionals who encounter patients with VHL.

  3. Abnormal Pap Smear and Diagnosis of High-Grade Vaginal Intraepithelial Neoplasia

    PubMed Central

    Sopracordevole, Francesco; Mancioli, Francesca; Clemente, Nicolò; De Piero, Giovanni; Buttignol, Monica; Giorda, Giorgio; Ciavattini, Andrea

    2015-01-01

    Abstract The aim of this study was to analyze the correlation between the first diagnosis of high-grade Vaginal Intraepithelial Neoplasia (HG-VaIN: VaIN 2–VaIN 3) and the cytological abnormalities on the referral pap smear. All the women with histological diagnosis of HG-VaIN consecutively referred to the Gynecological Oncology Unit of the Aviano National Cancer Institute (Aviano, Italy) from January 1991 to April 2014 and with a pap smear performed in the 3 months before the diagnosis were considered, and an observational cohort study was performed. A total of 87 women with diagnosis of HG-VaIN were identified. Major cytological abnormalities (HSIL and ASC-H) on the referral pap smear were significantly more frequent than lesser abnormalities (ASC-US and LSIL) in postmenopausal women (64.9% vs 36.7%, P = 0.02) and in women with a previous diagnosis of HPV-related cervical preinvasive or invasive lesions (70.5% vs 39.5%, P = 0.01). Diagnosis of VaIN 3 was preceded by major cytological abnormalities in most of the cases (72.7% vs 27.3%, P < 0.001). The diagnosis of HG-VaIN can be preceded by different abnormalities on referral pap smear. Major abnormalities are usually reported in postmenopausal women and in women with previous cervical HPV-related disease. However, ASC-US or LSIL do not exclude HG-VaIN, especially VaIN2. An accurate examination of the whole vaginal walls (or vaginal vault) must be performed in all the women who underwent colposcopy for an abnormal pap smear, and a biopsy of all suspicious areas is mandatory. PMID:26496321

  4. Abnormal Pap Smear and Diagnosis of High-Grade Vaginal Intraepithelial Neoplasia: A Retrospective Cohort Study.

    PubMed

    Sopracordevole, Francesco; Mancioli, Francesca; Clemente, Nicolò; De Piero, Giovanni; Buttignol, Monica; Giorda, Giorgio; Ciavattini, Andrea

    2015-10-01

    The aim of this study was to analyze the correlation between the first diagnosis of high-grade Vaginal Intraepithelial Neoplasia (HG-VaIN: VaIN 2-VaIN 3) and the cytological abnormalities on the referral pap smear.All the women with histological diagnosis of HG-VaIN consecutively referred to the Gynecological Oncology Unit of the Aviano National Cancer Institute (Aviano, Italy) from January 1991 to April 2014 and with a pap smear performed in the 3 months before the diagnosis were considered, and an observational cohort study was performed.A total of 87 women with diagnosis of HG-VaIN were identified. Major cytological abnormalities (HSIL and ASC-H) on the referral pap smear were significantly more frequent than lesser abnormalities (ASC-US and LSIL) in postmenopausal women (64.9% vs 36.7%, P = 0.02) and in women with a previous diagnosis of HPV-related cervical preinvasive or invasive lesions (70.5% vs 39.5%, P = 0.01). Diagnosis of VaIN 3 was preceded by major cytological abnormalities in most of the cases (72.7% vs 27.3%, P < 0.001).The diagnosis of HG-VaIN can be preceded by different abnormalities on referral pap smear. Major abnormalities are usually reported in postmenopausal women and in women with previous cervical HPV-related disease. However, ASC-US or LSIL do not exclude HG-VaIN, especially VaIN2. An accurate examination of the whole vaginal walls (or vaginal vault) must be performed in all the women who underwent colposcopy for an abnormal pap smear, and a biopsy of all suspicious areas is mandatory. PMID:26496321

  5. A1BG and C3 are overexpressed in patients with cervical intraepithelial neoplasia III.

    PubMed

    Canales, Norma Angélica Galicia; Marina, Vicente Madrid; Castro, Jorge Salmerón; Jiménez, Alfredo Antúnez; Mendoza-Hernández, Guillermo; McCARRON, Elizabeth Langley; Roman, Margarita Bahena; Castro-Romero, Julieta Ivone

    2014-08-01

    The present study aimed to analyze sera proteins in females with cervical intraepithelial neoplasia, grade III (CIN III) and in healthy control females, in order to identify a potential biomarker which detects lesions that have a greater probability of cervical transformation. The present study investigated five sera samples from females who were Human Papilloma Virus (HPV) 16(+) and who had been histopathologically diagnosed with CIN III, as well as five sera samples from healthy control females who were HPV-negative. Protein separation was performed using two-dimensional (2D) gel electrophoresis and the proteins were stained with Colloidal Coommassie Blue. Quantitative analysis was performed using ImageMaster 2D Platinum 6.0 software. Peptide sequence identification was performed using a nano-LC ESIMS/MS system. The proteins with the highest Mascot score were validated using western blot analysis in an additional 55 sera samples from the control and CIN III groups. The eight highest score spots that were found to be overexpressed in the CIN III sera group were identified as α-1-B glycoprotein (A1BG), complement component 3 (C3), a pro-apolipoprotein, two apolipoproteins and three haptoglobins. Only A1BG and C3 were validated using western blot analysis, and the bands were compared between the two groups using densitometry analysis. The relative density of the bands of A1BG and C3 was found to be greater in all of the serum samples from the females with CIN III, compared with those of the individuals in the control group. In summary, the present study identified two proteins whose expression was elevated in females with CIN III, suggesting that they could be used as biomarkers for CIN III. However, further investigations are required in order to assess the expression of A1BG and C3 in different pre-malignant lesions.

  6. A1BG and C3 are overexpressed in patients with cervical intraepithelial neoplasia III

    PubMed Central

    CANALES, NORMA ANGÉLICA GALICIA; MARINA, VICENTE MADRID; CASTRO, JORGE SALMERÓN; JIMÉNEZ, ALFREDO ANTÚNEZ; MENDOZA-HERNÁNDEZ, GUILLERMO; McCARRON, ELIZABETH LANGLEY; ROMAN, MARGARITA BAHENA; CASTRO-ROMERO, JULIETA IVONE

    2014-01-01

    The present study aimed to analyze sera proteins in females with cervical intraepithelial neoplasia, grade III (CIN III) and in healthy control females, in order to identify a potential biomarker which detects lesions that have a greater probability of cervical transformation. The present study investigated five sera samples from females who were Human Papilloma Virus (HPV) 16+ and who had been histopathologically diagnosed with CIN III, as well as five sera samples from healthy control females who were HPV-negative. Protein separation was performed using two-dimensional (2D) gel electrophoresis and the proteins were stained with Colloidal Coommassie Blue. Quantitative analysis was performed using ImageMaster 2D Platinum 6.0 software. Peptide sequence identification was performed using a nano-LC ESIMS/MS system. The proteins with the highest Mascot score were validated using western blot analysis in an additional 55 sera samples from the control and CIN III groups. The eight highest score spots that were found to be overexpressed in the CIN III sera group were identified as α-1-B glycoprotein (A1BG), complement component 3 (C3), a pro-apolipoprotein, two apolipoproteins and three haptoglobins. Only A1BG and C3 were validated using western blot analysis, and the bands were compared between the two groups using densitometry analysis. The relative density of the bands of A1BG and C3 was found to be greater in all of the serum samples from the females with CIN III, compared with those of the individuals in the control group. In summary, the present study identified two proteins whose expression was elevated in females with CIN III, suggesting that they could be used as biomarkers for CIN III. However, further investigations are required in order to assess the expression of A1BG and C3 in different pre-malignant lesions. PMID:25009667

  7. Pregnancy incidence and outcome before and after cervical intraepithelial neoplasia: a retrospective cohort study.

    PubMed

    Kalliala, Ilkka; Anttila, Ahti; Nieminen, Pekka; Halttunen, Mervi; Dyba, Tadeusz

    2014-12-01

    We performed a retrospective cohort study of 3530 women treated for cervical intraepithelial neoplasia (CIN) in Helsinki University Central Hospital, Finland, to investigate whether CIN treatment itself affects pregnancy incidence and outcome. We estimated the incidence of live births, miscarriages, extrauterine pregnancies, molar pregnancies, and termination of pregnancies (TOPs) before and after CIN treatment using nationwide registers. Women were followed up until death, emigration, sterilization, or the end of 2004. The comparison of incidence of pregnancy outcomes before and after the treatment was estimated by calculating hazard ratios (HRs) with conditional Poisson regression. After 76,162 woman-years of follow-up, the incidence of any pregnancy remained constant over CIN-treatment, HR 1.02 and 95% confidence interval (CI) 0.97-1.08, but the incidence of the first pregnancy was significantly elevated after treatment, HR 1.13, and 95% CI 1.03-1.23. The incidence of live births was significantly elevated after treatment, HR 1.08 and 95% CI 1.01-1.15. Incidence of miscarriages, TOPs, extrauterine pregnancies, and molar pregnancies was not elevated. TOPs was significantly increased in the first pregnancy, HR 1.40, 95% CI 1.15-1.72 and after treatment by the loop electrosurgical excision procedure (LEEP), HR 1.36, 95% CI 1.15-1.60. CIN treatment did not reduce pregnancy incidence and women had more live births after than before CIN treatment. TOPs was more common in the first pregnancy or after treatment by LEEP. We encourage research on the psychosocial consequences of CIN treatment also in other countries and settings.

  8. Identification of appropriate cone length to avoid positive cone margin in high grade cervical intraepithelial neoplasia

    PubMed Central

    Tsuda, Naotake; Nishio, Shin; Ushijima, Kimio

    2016-01-01

    Objective To identify key factors for predicting positive cone margin and appropriate cone length. Methods We retrospectively reviewed the margin status of patients who received conization with high grade cervical intraepithelial neoplasia, along with other factors such as patient age, parity, preoperative cytology, size of disease, type of transformation zone, and cone length from patient records. Cut-off value of cone length was analyzed in women younger than 40 years old because we design conization with minimum length especially for women who wish for future pregnancy. Cut-off value of cone length was defined as length corresponds to estimated probability of positive cone margin equal to 0.1 by logistic regression analysis with variables selected by stepwise methods. Results Among 300 patients, 75 patients had positive cone margin. Multivariable analysis revealed that squamous cell carcinoma at preoperative cytology (p=0.001), 2 or more quadrant disease (p=0.011), and shorter cone length (p<0.001) were risk factors for positive cone margin. Stepwise methods identified cone length and size of lesion as important variables. With this condition, cut-off value of cone length was estimated as 15 mm in single quadrant disease and 20 mm in 2 or more quadrant disease, respectively. Conclusion We identified the independent risk factors of positive cone margin and identified the cut-off value of cone length to avoid positive cone margin in women younger than 40 years old. Conization should be performed not only according to colposcopic findings including type of transformation zone but size of disease and cone length. PMID:27401478

  9. Human Papillomavirus Genotype-Specific Prevalence Across the Continuum of Cervical Neoplasia and Cancer

    PubMed Central

    Joste, Nancy E.; Ronnett, Brigitte M.; Hunt, William C.; Pearse, Amanda; Langsfeld, Erika; Leete, Thomas; Jaramillo, MaryAnn; Stoler, Mark H.; Castle, Philip E.; Wheeler, Cosette M.

    2014-01-01

    Background The New Mexico HPV Pap Registry was established to measure the impact of cervical cancer prevention strategies in the United States. Prior to widespread HPV vaccine implementation, we established the baseline prevalence for a broad spectrum of HPV genotypes across the continuum of cervical intraepithelial neoplasia (CIN) and cancer. Methods A population-based sample of 6,272 tissue specimens were tested for 37 HPV genotypes. The number of specimens tested within each diagnostic category was: 541 negative, 1,411 CIN grade 1 (CIN1), 2,226 CIN grade 2 (CIN2), and 2,094 CIN grade 3 (CIN3) or greater. Age-specific HPV prevalence was estimated within categories for HPV genotypes targeted by HPV vaccines. Results The combined prevalence of HPV genotypes included in the quadrivalent and nonavalent vaccines increased from 15.3% and 29.3% in CIN1 to 58.4% and 83.7% in CIN3, respectively. The prevalence of HPV types included in both vaccines tended to decrease with increasing age for CIN1, CIN2, CIN3, and squamous cell carcinoma, most notably for CIN3 and SCC. The six most common HPV types in descending order of prevalence were HPV-16, −31, −52, −58, −33, and −39 for CIN3 and HPV-16, −18, −31, −45, −52, and −33 for invasive cancers. Conclusions Health economic modeling of HPV vaccine impact should consider age-specific differences in HPV prevalence. Impact Population-based HPV prevalence in CIN is not well described but is requisite for longitudinal assessment of vaccine impact and to understand the effectiveness and performance of various cervical screening strategies in vaccinated and unvaccinated women. PMID:25363635

  10. LINE-1 Methylation Patterns as a Predictor of Postmolar Gestational Trophoblastic Neoplasia

    PubMed Central

    Lertkhachonsuk, Ruangsak; Paiwattananupant, Krissada; Tantbirojn, Patou; Rattanatanyong, Prakasit; Mutirangura, Apiwat

    2015-01-01

    Objective. To study the potential of long interspersed element-1 (LINE-1) methylation change in the prediction of postmolar gestational trophoblastic neoplasia (GTN). Methods. The LINE-1 methylation pattern from first trimester placenta, hydatidiform mole, and malignant trophoblast specimens were compared. Then, hydatidiform mole patients from 11999 to 2010 were classified into the following 2 groups: a remission group and a group that developed postmolar GTN. Specimens were prepared for a methylation study. The methylation levels and percentages of LINE-1 loci were evaluated for their sensitivity, specificity, and accuracy for the prediction of postmolar GTN. Results. First, 12 placentas, 38 moles, and 19 malignant trophoblast specimens were compared. The hydatidiform mole group had the highest LINE-1 methylation level (p = 0.003) and the uCuC of LINE-1 increased in the malignant trophoblast group (p ≤ 0.001). One hundred forty-five hydatidiform mole patients were classified as 103 remission and 42 postmolar GTN patients. The %mCuC and %uCmC of LINE-1 showed the lowest p value for distinguishing between the two groups (p < 0.001). The combination of the pretreatment β-hCG level (≥100,000 mIU/mL) with the %mCuC and %uCmC, sensitivity, specificity, PPV, NPV, and accuracy modified the levels to 60.0%, 92.2%, 77.4%, 83.8%, and 82.3%, respectively. Conclusions. A reduction in the partial methylation of LINE-1 occurs early before the clinical appearance of malignant transformation. The %mCuC and %uCmC of LINE-1s may be promising markers for monitoring hydatidiform moles before progression to GTN. PMID:26448937

  11. GNA15 expression in small intestinal neuroendocrine neoplasia: functional and signalling pathway analyses.

    PubMed

    Zanini, Sara; Giovinazzo, Francesco; Alaimo, Daniele; Lawrence, Ben; Pfragner, Roswitha; Bassi, Claudio; Modlin, Irvin; Kidd, Mark

    2015-05-01

    Gastroenteropancreatic neuroendocrine neoplasia (GEP-NEN) comprises a heterogeneous group of tumours that exhibit widely divergent biological behaviour. The identification of new targetable GPCR-pathways involved in regulating cell function could help to identify new therapeutic strategies. We assessed the function of a haematopoietic stem cell heterotrimeric G-protein, Gα15, in gut neuroendocrine cell models and examined the clinical implications of its over expression. Functional assays were undertaken to define the role of GNA15 in the small intestinal NEN cell line KRJ-I and in clinical samples from small intestinal NENs using quantitative polymerase chain reaction, western blot, proliferation and apoptosis assays, immunoprecipitation, immunohistochemistry (IHC) and automated quantitative analysis (AQUA). GNA15 was not expressed in normal neuroendocrine cells but was overexpressed in GEP-NEN cell lines. In KRJ-I cells, decreased expression of GNA15 was associated with inhibition of proliferation, activation of apoptosis and differential effects on pro-proliferative ERK, NFκB and Akt pathway signalling. Moreover, Gα15 was demonstrated to couple to the ß1 adrenergic receptor and modulated proliferative signals through this GPCR. Transcript and protein levels of GNA15 were significantly elevated in primary and metastatic tumours compared to normal mucosa and were particularly increased in low Ki-67 expressing tumours. IHC and AQUA revealed that a higher Gα15 expression was associated with a poorer survival. GNA15 may have a pathobiological role in SI-NENs. Targeting this signalling mediator could provide an opportunity for the development of new therapeutic strategies for this tumour type. PMID:25701539

  12. Prostatic atrophy: its spatial proximity to carcinoma and intraepithelial neoplasia based on annotation of digital slides.

    PubMed

    Iczkowski, Kenneth A; Torkko, Kathleen C; Wilson, R Storey; Lucia, M Scott; Bostwick, David G

    2014-01-01

    Whether atrophy is a precursor to high-grade prostatic intraepithelial neoplasia (HGPIN) and cancer is controversial. A virtual slide set comprising 48 prostatectomy cases was used to investigate associations among the amounts and spacing of these entities. Foci of atrophy without inflammation (A), atrophy with inflammation (AI), cancer (by patterns), and HGPIN were digitally annotated. Atrophy's proximity to cancer and HGPIN was assessed with two measurements: abutment (touching) or nearness (≤2 μm without touching). Area sums per specimen were computed for A, AI, cancer, and HGPIN. Abutment rates of AI and A foci to cancer were 23% versus 21% (p = NS); for nearness, 29% of AI foci were near to cancer versus 12% of A (P = .0001). Abutment or nearness of A and AI to HGPIN were in the 1.4% to 2.4% range. When A, AI, or HGPIN abutted cancer, it was disproportionately to Gleason grade 3 cancer foci even after adjusting for the lesser frequency of higher-grade cancer foci. Area sums of A, AI, or (A + AI) per specimen showed no correlations with those of HGPIN, and mostly negative ones with area sum and with tumor volume of cancer. In conclusion, atrophy with inflammation showed some preferential spatial association to cancer, although area sums of atrophy with or without inflammation correlated negatively with those of cancer. These divergent spatial associations suggest that atrophy and inflammation in biopsy specimens may have clinical relevance. The frequency of inflammatory atrophy (AI) merging with HGPIN was far less than reported previously, weakening the theory that AI gives rise to HGPIN. PMID:24157066

  13. Proteomic analysis of pancreatic intraepithelial neoplasia and pancreatic carcinoma in rat models

    PubMed Central

    Wang, Lei; Liu, Hai-Lin; Li, Ya; Yuan, Ping

    2011-01-01

    AIM: To detect the proteomic variabilities of pancreatic intraepithelial neoplasia (PanIN) and pancreatic carcinoma (PC) induced by 7,12-dimethylbenzanthracene (DMBA) in rat models and to identify potential biomarkers. METHODS: Sixty adult male Sprague Dawley rats were randomized into three groups. The rats had DMBA implanted into their pancreas for one (n = 20) or two months (n = 20) or assigned to the normal group (n = 20). The rats were killed after one or two months, and were evaluated histopathologically. Three tissue samples from each group of rats with either normal pancreas, PanIN (PanIN-2) or PC were examined by 2D-DIGE. The different expression spot features were analyzed by matrix-assisted laser desorption/ionization-time of flight/time of flight (MALDI-TOF/TOF) tandem mass spectrometry. The expression of enolase 1, a differentially expressed protein, was identified by immunohistochemistry. RESULTS: There was significant difference in the proportions of neoplastic changes between the 1- and 2-mogroups (P = 0.0488). There was an increase in the frequency of adenocarcinomas in the 2-mo group compared with the 1-mo group (P = 0.0309). No neoplastic changes were observed in any of the animals in the normal group. Enolase 1, pancreatic ELA3B, necdin, Hbp23, CHD3, hnRNP A2/B1, Rap80, and Gnb2l1 were up-regulated in the PanIN and PC tissues, and CEL, TPT1, NME2, PCK2, an unnamed protein product, and glycine C-acetyltransferase were down-regulated in the PanIN and PC tissues. The immunohistochemical results showed that enolase 1 expression was up-regulated in the pancreatic cancer tissues of rats and humans. CONCLUSION: The pancreatic protein expression changes induced by DMBA suggest potential molecular targets for the early diagnosis and treatment of PC. PMID:21472101

  14. CAHM, a long non-coding RNA gene hypermethylated in colorectal neoplasia.

    PubMed

    Pedersen, Susanne K; Mitchell, Susan M; Graham, Lloyd D; McEvoy, Aidan; Thomas, Melissa L; Baker, Rohan T; Ross, Jason P; Xu, Zheng-Zhou; Ho, Thu; LaPointe, Lawrence C; Young, Graeme P; Molloy, Peter L

    2014-08-01

    The CAHM gene (Colorectal Adenocarcinoma HyperMethylated), previously LOC100526820, is located on chromosome 6, hg19 chr6:163 834 097-163 834 982. It lacks introns, encodes a long non-coding RNA (lncRNA) and is located adjacent to the gene QKI, which encodes an RNA binding protein. Deep bisulphite sequencing of ten colorectal cancer (CRC) and matched normal tissues demonstrated frequent hypermethylation within the CAHM gene in cancer. A quantitative methylation-specific PCR (qMSP) was used to characterize additional tissue samples. With a threshold of 5% methylation, the CAHM assay was positive in 2/26 normal colorectal tissues (8%), 17/21 adenomas (81%), and 56/79 CRC samples (71%). A reverse transcriptase-qPCR assay showed that CAHM RNA levels correlated negatively with CAHM % methylation, and therefore CAHM gene expression is typically decreased in CRC. The CAHM qMSP assay was applied to DNA isolated from plasma specimens from 220 colonoscopy-examined patients. Using a threshold of 3 pg methylated genomic DNA per mL plasma, methylated CAHM sequences were detected in the plasma DNA of 40/73 (55%) of CRC patients compared with 3/73 (4%) from subjects with adenomas and 5/74 (7%) from subjects without neoplasia. Both the frequency of detection and the amount of methylated CAHM DNA released into plasma increased with increasing cancer stage. Methylated CAHM DNA shows promise as a plasma biomarker for use in screening for CRC.

  15. An exogenous retrovirus isolated from koalas with malignant neoplasias in a US zoo.

    PubMed

    Xu, Wenqin; Stadler, Cynthia K; Gorman, Kristen; Jensen, Nathaniel; Kim, David; Zheng, HaoQiang; Tang, Shaohua; Switzer, William M; Pye, Geoffrey W; Eiden, Maribeth V

    2013-07-01

    Leukemia and lymphoma account for more than 60% of deaths in captive koalas (Phascolarctos cinereus) in northeastern Australia. Although the endogenizing gammaretrovirus koala endogenous retrovirus (KoRV) was isolated from these koalas, KoRV has not been definitively associated with leukemogenesis. We performed KoRV screening in koalas from the San Diego Zoo, maintained for more than 45 y with very limited outbreeding, and the Los Angeles Zoo, maintained by continuously assimilating captive-born Australian koalas. San Diego Zoo koalas are currently free of malignant neoplasias and were infected with only endogenous KoRV, which we now term subtype "KoRV-A," whereas Los Angeles Zoo koalas with lymphomas/leukemias are infected in addition to KoRV-A by a unique KoRV we term subtype "KoRV-B." KoRV-B is most divergent in the envelope protein and uses a host receptor distinct from KoRV-A. KoRV-B also has duplicated enhancer regions in the LTR associated with increased pathology in gammaretroviruses. Whereas KoRV-A uses the sodium-dependent phosphate transporter 1 (PiT1) as a receptor, KoRV-B employs a different receptor, the thiamine transporter 1 (THTR1), to infect cells. KoRV-B is transmitted from dam to offspring through de novo infection, rather than via genetic inheritance like KoRV-A. Detection of KoRV-B in native Australian koalas should provide a history, and a mode for remediation, of leukemia/lymphoma currently endemic in this population.

  16. Counselling in multiple endocrine neoplasia syndromes: from individual experience to general guidelines.

    PubMed

    Lips, C J; Höppener, J W; Van Nesselrooij, B P; Van der Luijt, R B

    2005-01-01

    Counselling of patients and closely related family members has to take a central place in management of hereditary diseases, like multiple endocrine neoplasia (MEN) syndromes including von Hippel-Lindau (VHL) disease. In the strategy of health care, preventive medicine such as periodic clinical examination of families at-risk needs a high priority, because in general it is assumed that continuity in attendance is cost-effective. Counselling has to be based on individual medical experience of the doctor, adjusted to common guidelines and the findings in the family. Information leaflets, appropriate outpatient departments and an extensive network of specialists will facilitate continuity in care. Flow diagrams involving practical guidelines for diagnosis, treatment and follow up need to be applicable and after adjustment, should be accepted generally. Specially trained paramedics for counselling are required as a network that will guarantee periodic clinical examination and secure optimal prevention. Such paramedics will coordinate nationwide multidisciplinary guidance, and organize preventive and emergency cure for these patients. They will be supervised by expert clinicians in the field, and collaborate with specialists for social and psychological issues, patient organizations and clinical genetic centres. All of these professionals are responsible together for providing patients with up to date clinical information (via newsletters, Internet, etc.). Recently, in the Netherlands, a project was initiated to guarantee continuity in care and study the delivery of care. In order to realize this plan, funding has to be provided in the current research programme. In a future system support has to be obtained on a continuous base, preferably by the government and health care insurers and supervised by the national institute for health care. PMID:15606378

  17. Risk Factors for Persistent Cervical Intraepithelial Neoplasia Grades 1 and 2 Managed by Watchful Waiting

    PubMed Central

    Ho, Gloria Y.F.; Einstein, Mark H.; Romney, Seymour L.; Kadish, Anna S.; Abadi, Maria; Mikhail, Magdy; Basu, Jayasri; Thysen, Benjamin; Reimers, Laura; Palan, Prabhudas R.; Trim, Shelly; Soroudi, Nafisseh; Burk, Robert D.

    2013-01-01

    Objective This study examines risk factors for persistent cervical intraepithelial neoplasia (CIN) and whether human papillomavirus (HPV) testing predicts persistent lesions. Materials and Methods Women with histologically diagnosed CIN 1 or CIN 2 (n = 206) were followed every 3 months without treatment. HPV genotyping, plasma levels of ascorbic acid, and red blood cell folate were obtained. Cervical biopsy at 12 months determined the presence of CIN. Relative risk (RR) was estimated by log-linked binomial regression models. Results At 12 months, 70% of CIN 1 versus 54% of CIN 2 lesions spontaneously regressed (p< 0.001). Levels of folate or ascorbic acid were not associated with persistent CIN at 12 months. Compared to HPV negative women, those with multiple HPV types (RRs ranged from 1.68 to 2.17 at each follow-up visit) or high-risk types (RRs range = 1.74 to 2.09) were at increased risk for persistent CIN; women with HPV 16/18 had the highest risk (RRs range = 1.91 to 2.21). Persistent infection with a high-risk type was also associated with persistent CIN (RRs range = 1.50 – 2.35). Typing for high-risk HPVs at 6 months only had a sensitivity of 46% in predicting persistence of any lesions at 12 months. Conclusion Spontaneous regression of CIN 1 and CIN 2 occurs frequently within 12 months. HPV infection is the major risk factor for persistent CIN. However, HPV testing cannot reliably predict persistence of any lesion. PMID:21811178

  18. Indefinite for non‐invasive neoplasia lesions in gastric intestinal metaplasia: the immunophenotype

    PubMed Central

    Mauro Cassaro; Rugge, Massimo; Tieppo, Chiara; Giacomelli, Luciano; Velo, Daniela; Nitti, Donato

    2007-01-01

    Background In the Padova International Classification, gastric precancerous lesions are labelled as “indefinite for non‐invasive neoplasia” (Indef‐NiN) cytohistological alterations mimicking non‐invasive neoplasia (NiN), but lacking all the attributes required for a definite NiN categorisation. Aim To apply a panel of immunohistochemical (IHC) markers of cell proliferation (Mib1), intestinal differentiation (Cdx2), apoptosis (pro‐caspase 3) and cell immortalisation (hTERT) to compare the IHC profiles of a series of precancerous lesions arising in gastric intestinalised (ie, IM‐positive) glands. Materials and methods By applying the histological criteria consistently provided by both the Padova Classification and the World Health Organization International Agency, 112 consecutive cases were considered: intestinal metaplasia (IM; n = 54), Indef‐NiN in IM‐positive gastric glands (n = 28) and low‐grade (LG) NiN (n = 30). In each histological category, the expression of the marker was separately scored in superficial, proliferative and coil compartments. Results In all glandular compartments, Mib1, Cdx2, hTERT and pro‐caspase 3 were consistently more expressed in LG‐NiN than in either IM or Indef‐NiN lesions (analysis of variance: p<0.001). Significant ORs (calculated by ordinal logistic regression analysis for each glandular compartment) associated IM, Indef‐NiN and LG‐NiN with the expression of the considered markers. Conclusions A consistent overexpression (unrestricted to the proliferative zone) of IHC markers of cell proliferation, intestinal differentiation, decreased apoptosis and cell immortalisation differentiates LG‐NiN from both (simple) IM and Indef‐NiN (arising in IM). An increased proliferative activity in the proliferative zone discriminates Indef‐NiN lesions (ie, hyperproliferative IM) from IM. Such divergent IHC profiles may provide a rationale for scheduling follow‐up protocols more properly tailored on

  19. Subcellular distribution of peptides associated with gastric mucosal healing and neoplasia.

    PubMed

    Sarraf, C E; Alison, M R; Ansari, T W; Wright, N A

    1995-06-15

    The trefoil peptides pS2 and human spasmolytic peptide are putative growth factors, particularly associated with mucus-producing cells of the gastrointestinal tract including those of the stomach. The receptor for transforming growth factor alpha (TGF alpha) takes its name from one of its alternative ligands, epidermal growth factor, and is called the epidermal growth factor receptor. Although there is immunoreactive epidermal growth factor in the stomach, it is TGF alpha and the epidermal growth factor receptor that are abundant. Immunolabelling at electron microscope level allows for subcellular localisation of antigens; pS2 and human spasmolytic peptide co-localise to cytomembranes, including the Golgi apparatus, and thecae of surface/pit mucous cells. TGF alpha is abundant on the membranes of tubulovesicles of parietal cells and is also present in chief cells: in mucous producing cells it can be detected but not in association with mucous. The distribution of the epidermal growth factor receptor mimics that of TGF alpha but with preferential clustering on the basolateral membranes of gastric cells. The trefoil peptides are associated with healing and probably act, together with mucus, to protect the gastric mucosa and maintain a viable environment. TGF alpha, transduced via the epidermal growth factor receptor, inhibits gastric acid secretion, thus aids the trefoils in the maintenance of a gastric microenvironment conducive to healing after damage. TGF alpha, however, is also a potent mitogen; while this property plays a vital part in repairing mucosal defects, if this peptide or indeed its receptor are overexpressed, the result can be neoplasia.

  20. Favorable lifestyle before diagnosis associated with lower risk of screen-detected advanced colorectal neoplasia

    PubMed Central

    Knudsen, Markus D; de Lange, Thomas; Botteri, Edoardo; Nguyen, Dung-Hong; Evensen, Helge; Steen, Chloé B; Hoff, Geir; Bernklev, Tomm; Hjartåker, Anette; Berstad, Paula

    2016-01-01

    AIM: To investigate the association between adherence to health recommendations and detection of advanced colorectal neoplasia (ACN) in colorectal cancer (CRC) screening. METHODS: A total of 14832 women and men were invited to CRC screening, 6959 in the fecal immunochemical test arm and 7873 in the flexible sigmoidoscopy arm. These were also sent a self-reported lifestyle questionnaire to be completed prior to their first CRC screening. A lifestyle score was created to reflect current adherence to healthy behaviors in regard to smoking, body mass index, physical activity, alcohol consumption and food consumption, and ranged from zero (poorest) to six (best). Odds ratios (ORs) and 95%CIs were calculated using multivariable logistic regression to evaluate the association between the single lifestyle variables and the lifestyle score and the probability of detecting ACN. RESULTS: In all 6315 women and men completed the lifestyle questionnaire, 3323 (53%) in the FIT arm and 2992 (47%) in the FS arm. This was 89% of those who participated in screening. ACN was diagnosed in 311 (5%) participants of which 25 (8%) were diagnosed with CRC. For individuals with a lifestyle score of two, three, four, and five-six, the ORs (95%CI) for the probability of ACN detection were 0.82 (0.45-1.16), 0.43 (0.28-0.73), 0.41 (0.23-0.64), and 0.41 (0.22-0.73), respectively compared to individuals with a lifestyle score of zero-one. Of the single lifestyle factors, adherence to non-smoking and moderate alcohol intake were associated with a decreased probability of ACN detection compared to being a smoker or having a high alcohol intake 0.53 (0.42-0.68) and 0.63 (0.43-0.93) respectively. CONCLUSION: Adopted healthy behaviors were inversely associated with the probability of ACN detection. Lifestyle assessment might be useful for risk stratification in CRC screening. PMID:27468217

  1. [Clinical characteristics in multiple endocrine neoplasia type 1 in Japan: a review of 106 patients].

    PubMed

    Yoshimoto, K; Saito, S

    1991-07-20

    A review of 106 patients with multiple endocrine neoplasia (MEN) type 1 reported between 1966-1989 in Japan was conducted in order to clarify the natural history of this disease. Sporadic MEN 1 was found in 61 patients, and familial MEN 1 was found in 45 patients from 15 families. The mean ages at diagnosis of the two groups were 46.2 and 41.3 years, respectively, and the male to female ratio was 3:4. With regards to the involvement of the pituitary, parathyroid and endocrine pancreas, the combination of three endocrine glands was 31%, and that of two was 48%, in which the pituitary, parathyroid and endocrine pancreas had tumorous lesions in 60%, 88% and 63%, respectively. The first clinical manifestations of MEN 1 were the symptoms of hyperparathyroidism (32%), pituitary tumors (26%), peptic ulcer (28%) and hypoglycemia (13%). These symptoms appeared between 6 and 57 years of age (mean 34 years). The main clinical symptoms of the pituitary tumors were acromegaly and gigantism (37%), galactorrhea-amenorrhea syndrome (20%), Cushing's disease (10%) and visual disturbance due to compression of the tumor (20%). The clinical manifestations of hyperparathyroidism were mainly asymptomatic hypercalcemia (41%), nephrolithiasis (42%) and osteitis fibrosa (5%). In the patients with pancreatic tumor, Zollinger-Ellison syndrome (52%) and hypoglycemic symptoms (42%) were found. Tumors in the adrenal cortex, thyroid, carcinoid and lipoma were detected in association with MEN 1 in the frequencies of 28%, 21%, 9% and 5%, respectively. Death was reported in 37 patients between 9 and 86 years of age (mean 50.0 years). The cause of death was gastrointestinal bleeding and perforation (45%), surgery (24%) and disseminated carcinomatosis (18%). Recently, the gene predisposing to this syndrome has been assigned to chromosome 11 (11q13) in non-Japanese cases but not yet in Japanese MEN 1 patients. PMID:1679721

  2. The PapilloCheck Assay for Detection of High-Grade Cervical Intraepithelial Neoplasia.

    PubMed

    Crosbie, Emma J; Bailey, Andrew; Sargent, Alex; Gilham, Clare; Peto, Julian; Kitchener, Henry C

    2015-11-01

    Human papillomavirus (HPV) testing is used in primary cervical screening, as an adjunct to cervical cytology for the management of low grade abnormal cytology, and in a test of cure. PapilloCheck (Greiner Bio-One) is a PCR-based DNA microarray system that can individually identify 24 HPV types, including the 13 high-risk (HR) types identified by Hybrid Capture 2 (HC2). Here, we compare PapilloCheck with HC2 for the detection of high-grade cervical intraepithelial neoplasia (CIN2+) in a total of 8,610 cervical cytology samples from the ARTISTIC population-based cervical screening study. We performed a retrospective analysis of 3,518 cytology samples from round 1 ARTISTIC enriched for underlying CIN2+ (n = 723) and a prospective analysis of 5,092 samples from round 3 ARTISTIC. Discrepant results were tested using the Roche reverse line blot (RLB) or Linear Array (LA) assay. The relative sensitivity and specificity of HR PapilloCheck compared with that of HC2 for the detection of CIN2+ in women aged over 30 years were 0.94 (95% confidence interval [CI], 0.91, 0.97) and 1.05 (95% CI, 1.04, 1.05), respectively. HC2 missed 44/672 (7%) CIN2+ lesions, while HR PapilloCheck missed 74/672 (11%) CIN2+ lesions. Thirty-six percent of HC2-positive normal cytology samples were HR HPV negative by both PapilloCheck and RLB/LA, indicating that the use of HR PapilloCheck rather than HC2 in population-based primary screening would reduce the number of additional tests required (e.g., reflex cytology) in women where underlying CIN2+ is extremely unlikely. HR PapilloCheck could be a suitable HPV detection assay for use in the cervical screening setting. PMID:26338859

  3. Attributing oncogenic human papillomavirus genotypes to high-grade cervical neoplasia: which type causes the lesion?

    PubMed

    van der Marel, Jacolien; Berkhof, Johannes; Ordi, Jaume; Torné, Aureli; Del Pino, Marta; van Baars, Romy; Schiffman, Mark; Wentzensen, Nicolas; Jenkins, David; Quint, Wim G V

    2015-04-01

    Human papillomavirus (HPV) is found in most women with high-grade cervical intraepithelial neoplasia (CIN) 2/3 in cervical cytology and biopsies. Multiple high-risk HPV (hrHPV) genotypes are present in 15% to 50% of cytology samples. We have shown by laser-capture microscopy (LCM)-polymerase chain reaction (PCR) that each lesion is associated with a single hrHPV type. Attribution of hrHPV types to CIN2/3 is important to understand the oncogenic role of different types and the limitations of cytologic typing. We studied hrHPV genotypes in 257 women with histologic CIN2/3 referred on the basis of abnormal cytology. HPV typing was done on cytology and CIN2/3 biopsies. If the whole-tissue section of the biopsy was positive for multiple hrHPV types, LCM-PCR was performed. We found 181 (70%) single and 71 (28%) multiple hrHPV infections in cytology, with 5 (2%) cases HPV-positive only on whole-tissue section PCR. Of cases with multiple cytologic hrHPV infections, 47/71 (66%) showed a single type in CIN2/3 lesions. In total, in 232 of 257 (90%) women with CIN2/3, a single hrHPV type caused CIN2/3. One was nonattributable on the LCM level. The remaining 24 women had 2 or more contiguous or separated lesions, each associated with a single hrHPV infection. The probability of HPV16 being present in CIN2/3, if detected in cytology, was 0.96 (95% confidence interval=0.90-0.98). LCM-PCR confirms that only 9% of histologic CIN2/3 is associated with multiple hrHPV types, much less than cytology would indicate, and each lesion was associated with a single hrHPV infection.

  4. Tumor-associated glycoprotein distribution detected by monoclonal antibody B72.3 in salivary neoplasia.

    PubMed

    Brandwein, M S; Huvos, A G; Patil, J; Jagirdar, J

    1992-06-01

    The expression of tumor-associated glycoprotein (TAG-72), an oncofetal mucin-like tumor-associated glycoprotein derived from membrane-enriched fractions of metastatic breast carcinoma, has been detected by monoclonal antibody (MoAb) B72.3 in adenocarcinomas of breast, colon, lung, endometrium, pancreas, and ovary. The authors reported the scope of TAG-72 expression detected by MoAb B72.3 in salivary neoplasia. They examined 96 salivary lesions (53 malignant and 37 benign primary tumors, 2 metastatic carcinomas, and 4 other benign lesions) and 17 normal tissues from parotid glands and found: diffuse TAG-72 expression in 29 of 55 (53%) malignant tumors and 6 of 36 (17%) benign tumors and in no normal tissue; focal TAG-72 expression in 10 of 55 (17%) malignant salivary tumors, 10 of 37 (25%) benign salivary tumors (all benign mixed tumors), and 1 of 17 (6%) histologically normal parotid gland ducts. Any expression of TAG-72, whether diffuse or focal, was found to have a 71% sensitivity for detecting salivary malignant tumors, but an unacceptably low specificity for malignant lesions (57%). Alternatively, if only diffuse TAG-72 expression was regarded as indicative of malignancy, the specificity of diffuse TAG-72 expression was 86%, but sensitivity of detection decreased to 53%. The authors studied a subset of benign and malignant mixed tumors (BMT and MMT) and found that 12 of 15 (80%) MMT diffusely and strongly expressed TAG-72, 2 of 15 MMT (13%) expressed TAG-72 focally, and 1 MMT (7%) was nonreactive. By contrast, most BMT did not express TAG-72; only sparse, focal TAG-72 expression was seen in 10 of 27 (37%) BMT. If diffuse TAG-72 expression is considered indicative of malignancy, its sensitivity and specificity for malignant mixed tumors is 80% and 100%, respectively. The authors suggest that diffuse TAG-72 expression may resolve conflicts in determining whether or not a mixed tumor is malignant.

  5. Prediction of Spontaneous Regression of Cervical Intraepithelial Neoplasia Lesions Grades 2 and 3 by Proteomic Analysis

    PubMed Central

    Uleberg, Kai-Erik; Øvestad, Irene Tveiterås; Munk, Ane Cecilie; van Diermen, Bianca; Gudlaugsson, Einar; Janssen, Emiel A. M.; Hjelle, Anne; Baak, Jan P. A.

    2014-01-01

    Regression of cervical intraepithelial neoplasia (CIN) 2-3 to CIN 1 or less is associated with immune response as demonstrated by immunohistochemistry in formaldehyde-fixed paraffin-embedded (FFPE) biopsies. Proteomic analysis of water-soluble proteins in supernatants of biopsy samples with LC-MS (LTQ-Orbitrap) was used to identify proteins predictive of CIN2-3 lesions regression. CIN2-3 in the biopsies and persistence (CIN2-3) or regression (≤CIN1) in follow-up cone biopsies was validated histologically by two experienced pathologists. In a learning set of 20 CIN2-3 (10 regressions and 10 persistence cases), supernatants were depleted of seven high abundance proteins prior to unidimensional LC-MS/MS protein analysis. Mean protein concentration was 0.81 mg/mL (range: 0.55–1.14). Multivariate statistical methods were used to identify proteins that were able to discriminate between regressive and persistent CIN2-3. The findings were validated in an independent test set of 20 CIN2-3 (10 regressions and 10 persistence cases). Multistep identification criteria identified 165 proteins. In the learning set, zinc finger protein 441 and phospholipase D6 independently discriminated between regressive and persistent CIN2-3 lesions and correctly classified all 20 patients. Nine regression and all persistence cases were correctly classified in the validation set. Zinc finger protein 441 and phospholipase D6 in supernatant samples detected by LTQ-Orbitrap can predict regression of CIN2-3. PMID:25018881

  6. Eliminating a need for esophagectomy: endoscopic treatment of Barrett esophagus with early esophageal neoplasia.

    PubMed

    Lada, Michal J; Watson, Thomas J; Shakoor, Aqsa; Nieman, Dylan R; Han, Michelle; Tschoner, Andreas; Peyre, Christian G; Jones, Carolyn E; Peters, Jeffrey H

    2014-01-01

    Over the past several years, endoscopic ablation and resection have become a new standard of care in the management of Barrett esophagus (BE) with high-grade dysplasia (HGD) or intramucosal adenocarcinoma (IMC). Risk factors for failure of endoscopic therapy and the need for subsequent esophagectomy have not been well elucidated. The aims of this study were to determine the efficacy of radiofrequency ablation (RFA) with or without endoscopic mucosal resection (EMR) in the management of BE with HGD or IMC, to discern factors predictive of endoscopic treatment failure, and to assess the effect of endoscopic therapies on esophagectomy volume at our institution. Data were obtained retrospectively for all patients who underwent endoscopic therapies or esophagectomy for a diagnosis of BE with HGD or IMC in our department between January 1, 2004, and December 31, 2012. Complete remission (CR) of BE or HGD or IMC was defined as 2 consecutive biopsy sessions without BE or HGD or IMC and no subsequent recurrence. Recurrence was defined by the return of BE or HGD or IMC after initial remission. Progression was defined as worsening of HGD to IMC or worsening of IMC to submucosal neoplasia or beyond. Overall, 57 patients underwent RFA with or without EMR for BE with HGD (n = 45) or IMC (n = 12) between 2007 and 2012, with a median follow-up duration of 35.4 months (range: 18.5-52.0 months). The 57 patients underwent 181 ablation sessions and more than half (61%) of patients underwent EMR as a component of treatment. There were no major procedural complications or deaths, with only 2 minor complications including 1 symptomatic stricture requiring dilation. Multifocal HGD or IMC was present in 43% (25/57) of patients. CR of IMC was achieved in 100% (12/12) at a median of 6.1 months, CR of dysplasia was achieved in 79% (45/57) at a median of 11.5 months, and CR of BE was achieved in 49% (28/57) at a median of 18.4 months. Following initial remission, 28% of patients (16/57) had

  7. Interaction with Epithelial Cells Modifies Airway Macrophage Response to Ozone

    EPA Science Inventory

    The initial innate immune response to ozone (03) in the lung is orchestrated by structural cells, such as epithelial cells, and resident immune cells, such as airway macrophages (Macs). We developed an epithelial cell-Mac coculture model to investigate how epithelial cell-derived...

  8. Modular video endoscopy for in vivo cross-polarized and vital-dye fluorescence imaging of Barrett’s-associated neoplasia

    PubMed Central

    Pierce, Mark C.; Lee, Michelle H.; Polydorides, Alexandros D.; Flores, Raja M.; Anandasabapathy, Sharmila; Richards-Kortum, Rebecca R.

    2013-01-01

    Abstract. A modular video endoscope is developed and tested to allow imaging in different modalities. This system incorporates white light imaging (WLI), cross-polarized imaging (CPI), and vital-dye fluorescence imaging (VFI), using interchangeable filter modules. CPI and VFI are novel endoscopic modalities that probe mucosal features associated with Barrett’s neoplasia. CPI enhances vasculature, while VFI enhances glandular architecture. In this pilot study, we demonstrate the integration of these modalities by imaging areas of Barrett’s metaplasia and neoplasia in an esophagectomy specimen. We verify that those key image features are also observed during an in vivo surveillance procedure. CPI images demonstrate improved visualization of branching blood vessels associated with neoplasia. VFI images show glandular architecture with increased glandular effacement associated with neoplasia. Results suggests that important pathologic features seen in CPI and VFI are not visible during standard endoscopic white light imaging, and thus the modalities may be useful in future in vivo studies for discriminating neoplasia from Barrett’s metaplasia. We further demonstrate that the integrated WLI/CPI/VFI endoscope is compatible with complementary high-resolution endomicroscopy techniques such as the high-resolution microendoscope, potentially enabling two-step (“red-flag” widefield plus confirmatory high-resolution imaging) protocols to be enhanced. PMID:23370452

  9. Control of the epithelial stem cell epigenome: the shaping of epithelial stem cell identity.

    PubMed

    Iglesias-Bartolome, Ramiro; Callejas-Valera, Juan Luis; Gutkind, J Silvio

    2013-04-01

    The squamous epithelium covering the skin and oral mucosa relies on epithelial stem cells for tissue renewal. Dynamic changes in DNA methylation, histone methylation and acetylation, and higher order chromatin structure are required to preserve their self-renewal capacity while orchestrating the timely execution of cell differentiation programs. This complex network of epigenetic modifications shapes the epithelial stem cell identity and fate. Pathological alterations can be perceived by aberrant chromatin sensors, such as the INK4/ARF locus, which initiate tumor suppressive cell senescence programs, and can often result in epithelial stem cell exhaustion. Unveiling the mechanisms controlling the epigenome in epithelial stem cells may help protect against the loss of their tissue regenerative capacity, thereby preventing premature aging without increasing cancer risk. PMID:23434069

  10. Heterogeneity and stochastic growth regulation of biliary epithelial cells dictate dynamic epithelial tissue remodeling.

    PubMed

    Kamimoto, Kenji; Kaneko, Kota; Kok, Cindy Yuet-Yin; Okada, Hajime; Miyajima, Atsushi; Itoh, Tohru

    2016-01-01

    Dynamic remodeling of the intrahepatic biliary epithelial tissue plays key roles in liver regeneration, yet the cellular basis for this process remains unclear. We took an unbiased approach based on in vivo clonal labeling and tracking of biliary epithelial cells in the three-dimensional landscape, in combination with mathematical simulation, to understand their mode of proliferation in a mouse liver injury model where the nascent biliary structure formed in a tissue-intrinsic manner. An apparent heterogeneity among biliary epithelial cells was observed: whereas most of the responders that entered the cell cycle upon injury exhibited a limited and tapering growth potential, a select population continued to proliferate, making a major contribution in sustaining the biliary expansion. Our study has highlighted a unique mode of epithelial tissue dynamics, which depends not on a hierarchical system driven by fixated stem cells, but rather, on a stochastically maintained progenitor population with persistent proliferative activity. PMID:27431614

  11. Stromal-epithelial interactions in aging and cancer: Senescent fibroblasts alter epithelial cell differentiation

    SciTech Connect

    Parrinello, Simona; Coppe, Jean-Philippe; Krtolica, Ana; Campisi, Judith

    2004-07-14

    Cellular senescence suppresses cancer by arresting cells at risk for malignant tumorigenesis. However, senescent cells also secrete molecules that can stimulate premalignant cells to proliferate and form tumors, suggesting the senescence response is antagonistically pleiotropic. We show that premalignant mammary epithelial cells exposed to senescent human fibroblasts in mice irreversibly lose differentiated properties, become invasive and undergo full malignant transformation. Moreover, using cultured mouse or human fibroblasts and non-malignant breast epithelial cells, we show that senescent fibroblasts disrupt epithelial alveolar morphogenesis, functional differentiation, and branching morphogenesis. Further, we identify MMP-3 as the major factor responsible for the effects of senescent fibroblasts on branching morphogenesis. Our findings support the idea that senescent cells contribute to age-related pathology, including cancer, and describe a new property of senescent fibroblasts--the ability to alter epithelial differentiation--that might also explain the loss of tissue function and organization that is a hallmark of aging.

  12. Iris pigment epithelial cysts in a newborn

    PubMed Central

    Zargar, Shabnam; Prendiville, Kevin John; Martinez, Eladio

    2016-01-01

    Purpose: We report a case of iris pigment epithelial cysts in a newborn and discuss the importance of an accurate diagnosis for prevention of amblyopia. Methods: We describe a case of an abnormal red reflex seen on a newborn exam. Results: A full-term female born via normal spontaneous vaginal delivery without any complications was seen in the newborn nursery. She was noted to have an abnormal eye exam. Pupils were large with circular dark excrescences of the iris pigment epithelium. She was referred to a pediatric ophthalmologist where she was noted to fixate and follow faces. No afferent pupillary defect was seen. OD red reflex was normal whereas OS red reflex was blocked mostly by dark excrescences. A 2–3 mm dark brown lesion was seen in the OD iris and a 3–5 mm dark brown lesion was seen in the OS iris, consistent with a pupillary iris pigment epithelial cyst. Central visual axis was clear OU. Glaucoma was not present and patching was not performed. Observations and clinical photographs were recommended with follow-up in three months. Conclusion: Iris pigment epithelial cysts are uncommonly seen in children. The primary care provider first seeing a newborn must be aware of lesions obscuring a red reflex with appropriate follow-up. Follow-up in three months with IOP measurements is recommended. Iris pigment epithelial cysts in children may be a cause of amblyopia, thus prompt evaluation is important for prognostic purposes and the prevention of amblyopia. PMID:27625966

  13. The buffer capacity of airway epithelial secretions

    PubMed Central

    Kim, Dusik; Liao, Jie; Hanrahan, John W.

    2014-01-01

    The pH of airway epithelial secretions influences bacterial killing and mucus properties and is reduced by acidic pollutants, gastric reflux, and respiratory diseases such as cystic fibrosis (CF). The effect of acute acid loads depends on buffer capacity, however the buffering of airway secretions has not been well characterized. In this work we develop a method for titrating micro-scale (30 μl) volumes and use it to study fluid secreted by the human airway epithelial cell line Calu-3, a widely used model for submucosal gland serous cells. Microtitration curves revealed that HCO−3 is the major buffer. Peak buffer capacity (β) increased from 17 to 28 mM/pH during forskolin stimulation, and was reduced by >50% in fluid secreted by cystic fibrosis transmembrane conductance regulator (CFTR)-deficient Calu-3 monolayers, confirming an important role of CFTR in HCO−3 secretion. Back-titration with NaOH revealed non-volatile buffer capacity due to proteins synthesized and released by the epithelial cells. Lysozyme and mucin concentrations were too low to buffer Calu-3 fluid significantly, however model titrations of porcine gastric mucins at concentrations near the sol-gel transition suggest that mucins may contribute to the buffer capacity of ASL in vivo. We conclude that CFTR-dependent HCO−3 secretion and epithelially-derived proteins are the predominant buffers in Calu-3 secretions. PMID:24917822

  14. Maintaining epithelial stemness with p63.

    PubMed

    Melino, Gerry; Memmi, Elisa Maria; Pelicci, Pier Giuseppe; Bernassola, Francesca

    2015-07-28

    In stratified epithelial and glandular tissues, homeostasis relies on the self-renewing capacity of stem cells, which are within the basal layer. The p53 family member p63 is an indispensable transcription factor for epithelial morphogenesis and stemness. A splice variant of the transcription factor p63 that lacks an amino-terminal domain, ΔNp63, is selectively found in the basal compartments of several ectoderm-derived tissues such as stratified and glandular epithelia, in which it is required for the replenishment of stem cells. Thus far, the transcriptional programs downstream of p63 in stemness regulation remain incompletely defined. Unveiling the molecular basis of stem cell self-renewal may be relevant in understanding how this process may contribute to cancer development. In this review, we specifically highlight experimental investigations, which suggest that p63 is a marker of normal epithelial stem cells and describe p63 transcriptional targets that may be involved in stemness regulation. Finally, we discuss relevant findings implicating p63 in epithelial cancer stem cell biology. PMID:26221054

  15. Multimodality approach to optical early detection and mapping of oral neoplasia

    NASA Astrophysics Data System (ADS)

    Ahn, Yeh-Chan; Chung, Jungrae; Wilder-Smith, Petra; Chen, Zhongping

    2011-07-01

    Early detection of cancer remains the best way to ensure patient survival and quality of life. Squamous cell carcinoma is usually preceded by dysplasia presenting as white, red, or mixed red and white epithelial lesions on the oral mucosa (leukoplakia, erythroplakia). Dysplastic lesions in the form of erythroplakia can carry a risk for malignant conversion of 90%. A noninvasive diagnostic modality would enable monitoring of these lesions at regular intervals and detection of treatment needs at a very early, relatively harmless stage. The specific aim of this work was to test a multimodality approach [three-dimensional optical coherence tomography (OCT) and polarimetry] to noninvasive diagnosis of oral premalignancy and malignancy using the hamster cheek pouch model (nine hamsters). The results were compared to tissue histopathology. During carcinogenesis, epithelial down grow, eventual loss of basement membrane integrity, and subepithelial invasion were clearly visible with OCT. Polarimetry techniques identified a four to five times increased retardance in sites with squamous cell carcinoma, and two to three times greater retardance in dysplastic sites than in normal tissues. These techniques were particularly useful for mapping areas of field cancerization with multiple lesions, as well as lesion margins.

  16. Multimodality approach to optical early detection and  mapping of oral neoplasia

    PubMed Central

    Ahn, Yeh-Chan; Chung, Jungrae; Wilder-Smith, Petra; Chen, Zhongping

    2011-01-01

    Early detection of cancer remains the best way to ensure patient survival and quality of life. Squamous cell carcinoma is usually preceded by dysplasia presenting as white, red, or mixed red and white epithelial lesions on the oral mucosa (leukoplakia, erythroplakia). Dysplastic lesions in the form of erythroplakia can carry a risk for malignant conversion of 90%. A noninvasive diagnostic modality would enable monitoring of these lesions at regular intervals and detection of treatment needs at a very early, relatively harmless stage. The specific aim of this work was to test a multimodality approach [three-dimensional optical coherence tomography (OCT) and polarimetry] to noninvasive diagnosis of oral premalignancy and malignancy using the hamster cheek pouch model (nine hamsters). The results were compared to tissue histopathology. During carcinogenesis, epithelial down grow, eventual loss of basement membrane integrity, and subepithelial invasion were clearly visible with OCT. Polarimetry techniques identified a four to five times increased retardance in sites with squamous cell carcinoma, and two to three times greater retardance in dysplastic sites than in normal tissues. These techniques were particularly useful for mapping areas of field cancerization with multiple lesions, as well as lesion margins. PMID:21806268

  17. New Insights into the Mechanism of Action of Aspirin in the Prevention of Colorectal Neoplasia.

    PubMed

    Di Francesco, Luigia; López Contreras, Luilli Antonio; Sacco, Angela; Patrignani, Paola

    2015-01-01

    The results of clinical studies have shown that the chronic administration of aspirin, even at the lowdoses (75-100 mg daily) recommended for the prevention of cardiovascular disease, is associated with a reduction of cancer incidence and mortality, in particular colorectal cancer (CRC). The mechanism of action of aspirin as an antineoplastic agent remains controversial. However, data of clinical pharmacology and several features of the chemopreventive effect of aspirin, emerged from clinical trials, suggest that the antiplatelet effect of aspirin plays a central role in its anticancer effects. In addition to their contribution to tumor metastasis, platelets may play a role in the early phases of tumorigenesis. In response to lifestyle and environment factors, intestinal epithelial damage/ dysfunction may be associated with platelet activation, initially as a mechanism to repair the damage. However, if the platelet response is unconstrained, it may contribute to the development of chronic inflammation. Altogether these events lead to alter the normal functions of intestinal epithelial cells and may translate into cellular transformation through several mechanisms, including the overexpression of cyclooxygenase(COX)-2 and epidermal growth factor receptor (EGFR), which are considered early events in colorectal tumorigenesis. Thus, antiplatelet agents may play a role in the prevention of CRC by modifying epigenetic events involved in early phases of colorectal tumorigenesis. Finally, we carried out a critical review of the literature on off-target mechanisms of aspirin action as anticancer drug. PMID:26369679

  18. Assessment of the "fish tumors or other deformities" beneficial use impairment in brown bullhead (Ameiurus nebulosus): II. Liver neoplasia

    USGS Publications Warehouse

    Blazer, V.S.; Rafferty, S.D.; Baumman, P.C.; Smith, S.B.; Obert, E.C.

    2009-01-01

    Liver pathology of fishes, including neoplastic and preneoplastic lesions, is widely used as an indicator of exposure to anthropogenic contaminants. By definition, the "fish tumor or other deformities" beneficial use impairment (BUI) at Great Lakes Areas of Concern (AOC) includes neoplastic and preneoplastic liver lesions in brown bullhead (Ameiurus nebulosus) or suckers. Unfortunately, adequate guidelines for defining neoplastic and preneoplastic liver lesions or determining rates at unimpacted control sites were not provided and different criteria have been used. In some cases, only neoplastic changes were used to calculate tumor prevalence, in some both neoplastic and preneoplastic changes and in some it is difficult to determine which changes were included. Using standardized criteria, the prevalence of liver neoplasia was compared at eight AOC during 1998-2000. The Cuyahoga River had the highest prevalence (25.0%), while the Maumee River had the lowest (3.9%). The Buffalo (4.8%), Detroit (5.9%), Ashtabula (6.8%), Niagara (7.5%) and Black (8.9%) rivers were intermediate, as was Presque Isle Bay (7.1%). From 2002 to 2007 the prevalence of liver neoplasia at Presque Isle Bay ranged from a low of 2.1% (2002) to a high of 12.0% (2007). Non-AOC sites, as potential reference sites, also were monitored during this time. By combining years and sites, the prevalence of liver neoplasia in bullhead (aged 2 to 12 years) at inland lakes was 0.7%, at bays/harbors was 1.6% and at tributary sites was 4.1%. This is the same trend (inland lakes < bays/harbors < tributaries < Presque Isle Bay) noted for orocutaneous neoplasms.

  19. Linkage to chromosome 2q32.2-q33.3 in familial serrated neoplasia (Jass syndrome).

    PubMed

    Roberts, Aedan; Nancarrow, Derek; Clendenning, Mark; Buchanan, Daniel D; Jenkins, Mark A; Duggan, David; Taverna, Darin; McKeone, Diane; Walters, Rhiannon; Walsh, Michael D; Young, Bruce W; Jass, Jeremy R; Rosty, Christophe; Gattas, Michael; Pelzer, Elise; Hopper, John L; Goldblatt, Jack; George, Jill; Suthers, Graeme K; Phillips, Kerry; Parry, Susan; Woodall, Sonja; Arnold, Julie; Tucker, Kathy; Muir, Amanda; Drini, Musa; Macrae, Finlay; Newcomb, Polly; Potter, John D; Pavluk, Erika; Lindblom, Annika; Young, Joanne P

    2011-06-01

    Causative genetic variants have to date been identified for only a small proportion of familial colorectal cancer (CRC). While conditions such as Familial Adenomatous Polyposis and Lynch syndrome have well defined genetic causes, the search for variants underlying the remainder of familial CRC is plagued by genetic heterogeneity. The recent identification of families with a heritable predisposition to malignancies arising through the serrated pathway (familial serrated neoplasia or Jass syndrome) provides an opportunity to study a subset of familial CRC in which heterogeneity may be greatly reduced. A genome-wide linkage screen was performed on a large family displaying a dominantly-inherited predisposition to serrated neoplasia genotyped using the Affymetrix GeneChip Human Mapping 10 K SNP Array. Parametric and nonparametric analyses were performed and resulting regions of interest, as well as previously reported CRC susceptibility loci at 3q22, 7q31 and 9q22, were followed up by finemapping in 10 serrated neoplasia families. Genome-wide linkage analysis revealed regions of interest at 2p25.2-p25.1, 2q24.3-q37.1 and 8p21.2-q12.1. Finemapping linkage and haplotype analyses identified 2q32.2-q33.3 as the region most likely to harbour linkage, with heterogeneity logarithm of the odds (HLOD) 2.09 and nonparametric linkage (NPL) score 2.36 (P = 0.004). Five primary candidate genes (CFLAR, CASP10, CASP8, FZD7 and BMPR2) were sequenced and no segregating variants identified. There was no evidence of linkage to previously reported loci on chromosomes 3, 7 and 9.

  20. Outcomes from a prospective trial of endoscopic radiofrequency ablation of early squamous cell neoplasia of the esophagus

    PubMed Central

    Bergman, Jacques JGHM; Zhang, Yueming; He, Shun; Weusten, Bas; Xue, Liyan; Fleischer, David E; Lu, Ning; Dawsey, Sanford M; Wang, Gui-Qi

    2012-01-01

    Background Radiofrequency ablation (RFA) is safe and effective for eradicating neoplasia in Barrett’s esophagus. Objective Evaluate RFA for eradicating early esophageal squamous cell neoplasia (ESCN) defined as moderate- and high-grade squamous intraepithelial neoplasia (MGIN, HGIN) and early flat-type esophageal squamous cell carcinoma (ESCC). Design Prospective cohort study. Setting Tertiary referral center. Patients Esophageal unstained lesions (USLs) were identified using Lugol’s chromoendoscopy. Inclusion: at least 1 flat (type 0-IIb) USL ≥3cm, USL-bearing esophagus ≤12 cm, and a consensus diagnosis of MGIN, HGIN, or ESCC by two expert GI pathologists. Exclusion: prior endoscopic resection or ablation, stricture, or any non-flat mucosa. Interventions Circumferential RFA creating a continuous treatment area (TA) including all USLs. At 3-month intervals thereafter, chromoendoscopy with biopsies, followed by focal RFA of USLs, if present. Main outcome measures Complete response (CR) at 12 months, defined as absence of MGIN, HGIN or ESCC in TA; CR after one RFA session; neoplastic progression from baseline; and adverse events. Results 29 patients (14 male, mean age 60.3 years) with MGIN (18), HGIN (10), or ESCC (1) participated. Mean USL length was 6.2 cm (TA 8.2 cm). At 3-months, after one RFA session, 86% of patients (25/29) were CR. At 12-months, 97% (28/29) of patients were CR. There was no neoplastic progression. There were 4 strictures, all dilated to resolution. Limitations Single center study with limited number of patients. Conclusions In patients with early ESCN (MGIN, HGIN, flat-type ESCC), RFA was associated with a high rate of histological complete response (97% of patients), no neoplastic progression, and an acceptable adverse event profile. PMID:21839994

  1. Dietary Supplementation with Fresh Pineapple Juice Decreases Inflammation and Colonic Neoplasia in IL-10-deficient Mice with Colitis

    PubMed Central

    Hale, Laura P.; Chichlowski, Maciej; Trinh, Chau T.; Greer, Paula K.

    2010-01-01

    Background Bromelain, a mixture of proteolytic enzymes typically derived from pineapple stem, decreases production of pro-inflammatory cytokines and leukocyte homing to sites of inflammation. We previously showed that short-term oral treatment with bromelain purified from pineapple stem decreased the severity of colonic inflammation in C57BL/6 Il10−/− mice with chronic colitis. Since fresh pineapple fruit contains similar bromelain enzymes but at different proportions, this study aimed to determine whether long-term dietary supplementation with pineapple (supplied as juice) could decrease colon inflammation and neoplasia in Il10−/− mice with chronic colitis as compared with bromelain derived from stem. Results Experimental mice readily consumed fresh pineapple juice at a level that generated mean stool proteolytic activities equivalent to 16 mg bromelain purified from stem, while control mice received boiled juice with inactive enzymes. Survival was increased in the group supplemented with fresh rather than boiled juice (p = 0.01). Mice that received fresh juice also had decreased histologic colon inflammation scores and a lower incidence of inflammation-associated colonic neoplasia (35% vs. 66%; p< 0.02), with fewer neoplastic lesions/colon (p = 0.05). Flow cytometric analysis of murine splenocytes exposed to fresh pineapple juice in vitro demonstrated proteolytic removal of cell surface molecules that can affect leukocyte trafficking and activation. Conclusions These results demonstrate that long-term dietary supplementation with fresh or unpasteurized frozen pineapple juice with proteolytically active bromelain enzymes is safe and decreases inflammation severity and the incidence and multiplicity of inflammation-associated colonic neoplasia in this commonly used murine model of inflammatory bowel disease. PMID:20848493

  2. Protons sensitize epithelial cells to mesenchymal transition.

    PubMed

    Wang, Minli; Hada, Megumi; Saha, Janapriya; Sridharan, Deepa M; Pluth, Janice M; Cucinotta, Francis A

    2012-01-01

    Proton radiotherapy has gained more favor among oncologists as a treatment option for localized and deep-seated tumors. In addition, protons are a major constituent of the space radiation astronauts receive during space flights. The potential for these exposures to lead to, or enhance cancer risk has not been well studied. Our objective is to study the biological effects of low energy protons on epithelial cells and its propensity to enhance transforming growth factor beta 1 (TGFβ1)-mediated epithelial-mesenchymal transition (EMT), a process occurring during tumor progression and critical for invasion and metastasis. Non-transformed mink lung epithelial cells (Mv1Lu) and hTERT- immortalized human esophageal epithelial cells (EPC) were used in this study. EMT was identified by alterations in cell morphology, EMT-related gene expression changes determined using real-time PCR, and EMT changes in specific cellular markers detected by immunostaining and western blotting. Although TGFβ1 treatment alone is able to induce EMT in both Mv1Lu and EPC cells, low energy protons (5 MeV) at doses as low as 0.1 Gy can enhance TGFβ1 induced EMT. Protons alone can also induce a mild induction of EMT. SD208, a potent TGFβ Receptor 1 (TGFβR1) kinase inhibitor, can efficiently block TGFβ1/Smad signaling and attenuate EMT induction. We suggest a model for EMT after proton irradiation in normal and cancerous tissue based on our results that showed that low and high doses of protons can sensitize normal human epithelial cells to mesenchymal transition, more prominently in the presence of TGFβ1, but also in the absence of TGFβ1.

  3. [Epithelial-mesenchymal transition in cancer progression].

    PubMed

    Gos, Monika; Miłoszewska, Joanna; Przybyszewska, Małgorzata

    2009-01-01

    According to recently published data, the epithelial-mesenchymal transition--a process important for embryonic development, may be involved in many pathological processes such as wound healing, tissue fibrosis or cancer progression. The EMT process in cell is driven by growth factors (EGF, PDGF, HGF) or other signaling proteins such as TGF-beta, sonic hedgehog (Shh), Wnt/beta-catenin and extracellular matrix (ECM) components that may stimulate cellular growth and migration. During cancer progression, the EMT process is necessary to the conversion of benign tumor to aggressive and highly invasive cancer. This is due to complex changes in cancer cells and their microenvironment that lead to dissolution of intracellular junctions and their detachment from basolateral membrane, and changes in the interactions between cancer cells and ECM. The loss of adhesion is accompanied by molecular and morphologic changes in cancer cells that are essential for the phenotypic change from epithelial to mesenchymal one, and the acquirement of higher migration and invasion potential. During the colonization of distant sites, a reverse process mesenchymal-epithelial transition (MET) takes place and metastatic cancer cells again acquire the epithelial phenotype. The EMT in cancer progression is not only specific for cancer cells. It has been suggested that also cells within tumor microenvironment e.g. cancer associated fibroblasts (CAF) are generated in part from normal epithelial cells in EMT process. The understanding of the role of EMT and MET processes in cancer progression and their relationship with cancer stem cells, cancer associated fibroblasts and other stroma cells might lead to the discovery of new, targeted cancer therapies.

  4. Protons Sensitize Epithelial Cells to Mesenchymal Transition

    PubMed Central

    Wang, Minli; Hada, Megumi; Saha, Janapriya; Sridharan, Deepa M.; Pluth, Janice M.; Cucinotta, Francis A.

    2012-01-01

    Proton radiotherapy has gained more favor among oncologists as a treatment option for localized and deep-seated tumors. In addition, protons are a major constituent of the space radiation astronauts receive during space flights. The potential for these exposures to lead to, or enhance cancer risk has not been well studied. Our objective is to study the biological effects of low energy protons on epithelial cells and its propensity to enhance transforming growth factor beta 1 (TGFβ1)-mediated epithelial-mesenchymal transition (EMT), a process occurring during tumor progression and critical for invasion and metastasis. Non-transformed mink lung epithelial cells (Mv1Lu) and hTERT- immortalized human esophageal epithelial cells (EPC) were used in this study. EMT was identified by alterations in cell morphology, EMT-related gene expression changes determined using real-time PCR, and EMT changes in specific cellular markers detected by immunostaining and western blotting. Although TGFβ1 treatment alone is able to induce EMT in both Mv1Lu and EPC cells, low energy protons (5 MeV) at doses as low as 0.1 Gy can enhance TGFβ1 induced EMT. Protons alone can also induce a mild induction of EMT. SD208, a potent TGFβ Receptor 1 (TGFβR1) kinase inhibitor, can efficiently block TGFβ1/Smad signaling and attenuate EMT induction. We suggest a model for EMT after proton irradiation in normal and cancerous tissue based on our results that showed that low and high doses of protons can sensitize normal human epithelial cells to mesenchymal transition, more prominently in the presence of TGFβ1, but also in the absence of TGFβ1. PMID:22844446

  5. Epithelial-mesenchymal transition in malignant mesothelioma.

    PubMed

    Fassina, Ambrogio; Cappellesso, Rocco; Guzzardo, Vincenza; Dalla Via, Lisa; Piccolo, Stefano; Ventura, Laura; Fassan, Matteo

    2012-01-01

    Epithelial-mesenchymal transition is a physiopathological process by which epithelial cells acquire mesenchymal shape and properties. Malignant mesothelioma is histologically characterized by the concomitant presence of epithelioid and sarcomatoid features, the latter being associated to worse prognosis, thus suggesting a role of epithelial-mesenchymal transition in this dual phenotype. We studied 109 malignant mesotheliomas (58 epithelioid, 26 sarcomatoid, and 25 biphasic) by immunohistochemistry and qRT-PCR analysis, and demonstrated a substantial switch from epithelial markers (E-cadherin, β-catenin, and cytokeratins 5/6) to mesenchymal markers (N-cadherin, vimentin, α-smooth muscle actin, Snail, Slug, Twist, ZEB1, ZEB2, S100A4, MMP2, and MMP9) through epithelioid to biphasic and sarcomatoid histotypes. In agreement with these findings, the ectopic expression of miR-205 (a repressor of ZEB1 and ZEB2 expression) in MeT-5A (mesothelial cell line), H2452 (an epithelioid malignant mesothelioma cell line) and MSTO-211H (a biphasic malignant mesothelioma cell line) not only induced a significant reduction of ZEB1 and ZEB2 and a consequent up-regulation of E-cadherin gene expression, but also inhibited migration and invasion. Moreover, miR-205 was significantly down-regulated in biphasic and sarcomatoid histotypes (qRT-PCR and in situ hybridization analyses). Collectively, our findings indicate that epithelial-mesenchymal transition has a significant part in the morphological features of malignant mesothelioma. In particular, miR-205 down-regulation correlated significantly with both a mesenchymal phenotype and a more aggressive behavior.

  6. Klebsiella pneumoniae Is Able to Trigger Epithelial-Mesenchymal Transition Process in Cultured Airway Epithelial Cells

    PubMed Central

    Leone, Laura; Mazzetta, Francesca; Martinelli, Daniela; Valente, Sabatino; Alimandi, Maurizio; Raffa, Salvatore; Santino, Iolanda

    2016-01-01

    The ability of some bacterial pathogens to activate Epithelial-Mesenchymal Transition normally is a consequence of the persistence of a local chronic inflammatory response or depends on a direct interaction of the pathogens with the host epithelial cells. In this study we monitored the abilities of the K. pneumoniae to activate the expression of genes related to EMT-like processes and the occurrence of phenotypic changes in airway epithelial cells during the early steps of cell infection. We describe changes in the production of intracellular reactive oxygen species and increased HIF-1α mRNA expression in cells exposed to K. pneumoniae infection. We also describe the upregulation of a set of transcription factors implicated in the EMT processes, such as Twist, Snail and ZEB, indicating that the morphological changes of epithelial cells already appreciable after few hours from the K. pneumoniae infection are tightly regulated by the activation of transcriptional pathways, driving epithelial cells to EMT. These effects appear to be effectively counteracted by resveratrol, an antioxidant that is able to exert a sustained scavenging of the intracellular ROS. This is the first report indicating that strains of K. pneumoniae may promote EMT-like programs through direct interaction with epithelial cells without the involvement of inflammatory cells. PMID:26812644

  7. Human odontogenic epithelial cells derived from epithelial rests of Malassez possess stem cell properties.

    PubMed

    Tsunematsu, Takaaki; Fujiwara, Natsumi; Yoshida, Maki; Takayama, Yukihiro; Kujiraoka, Satoko; Qi, Guangying; Kitagawa, Masae; Kondo, Tomoyuki; Yamada, Akiko; Arakaki, Rieko; Miyauchi, Mutsumi; Ogawa, Ikuko; Abiko, Yoshihiro; Nikawa, Hiroki; Murakami, Shinya; Takata, Takashi; Ishimaru, Naozumi; Kudo, Yasusei

    2016-10-01

    Epithelial cell rests of Malassez (ERM) are quiescent epithelial remnants of the Hertwig's epithelial root sheath (HERS) that are involved in the formation of tooth roots. ERM cells are unique epithelial cells that remain in periodontal tissues throughout adult life. They have a functional role in the repair/regeneration of cement or enamel. Here, we isolated odontogenic epithelial cells from ERM in the periodontal ligament, and the cells were spontaneously immortalized. Immortalized odontogenic epithelial (iOdE) cells had the ability to form spheroids and expressed stem cell-related genes. Interestingly, iOdE cells underwent osteogenic differentiation, as demonstrated by the mineralization activity in vitro in mineralization-inducing media and formation of calcification foci in iOdE cells transplanted into immunocompromised mice. These findings suggest that a cell population with features similar to stem cells exists in ERM and that this cell population has a differentiation capacity for producing calcifications in a particular microenvironment. In summary, iOdE cells will provide a convenient cell source for tissue engineering and experimental models to investigate tooth growth, differentiation, and tumorigenesis. PMID:27479086

  8. Pituitary Prolactinoma Imaged by 99mTc-Sestamibi SPECT/CT in a Multiple Endocrine Neoplasia Type 1 Patient.

    PubMed

    Pan, Yu; Lv, Jing; Guo, Rui; Pan, Mengyi; Zhang, Yifan

    2016-06-01

    A 35-year-old woman who had undergone bilateral inferior parathyroidectomy for primary hyperparathyroidism was referred to our hospital to evaluate the cause of irregular menses, galactorrhea, and paroxysmal headache. Multiple endocrine neoplasia type 1 was then suspected for the high levels of plasma prolactin, parathyroid hormone, serum calcium, insulin, and related symptoms. A Tc-sestamibi SPECT/CT acquired to evaluate parathyroid glands unexpectedly revealed an increased accumulation in the pituitary gland, which was further confirmed by enhanced magnetic resonance imaging as a pituitary microadenoma. Bromocriptine treatment gradually reduced the prolactin level.

  9. Fertility and early pregnancy outcomes after treatment for cervical intraepithelial neoplasia: systematic review and meta-analysis

    PubMed Central

    Mitra, Anita; Arbyn, Marc; Stasinou, Sofia Melina; Martin-Hirsch, Pierre; Bennett, Phillip; Paraskevaidis, Evangelos

    2014-01-01

    Objective To determine the impact of cervical excision for cervical intraepithelial neoplasia on fertility and early pregnancy outcomes. Design Systematic review and meta-analysis of cohort studies. Data sources Medline and Embase. Eligibility criteria Studies assessing fertility and early pregnancy outcomes in women with a history of treatment for cervical intraepithelial neoplasia versus untreated women. We classified the included studies according to treatment type and fertility or early pregnancy endpoint. Analysis Pooled relative risks and 95% confidence intervals using a random effect model, and interstudy heterogeneity with I2 statistics. Results 15 studies fulfilled the inclusion criteria and were included. The meta-analysis did not provide any evidence that treatment for cervical intraepithelial neoplasia adversely affected the chances of conception. The overall pregnancy rate was higher for treated women than for untreated women (four studies; 43% v 38%, pooled relative risk 1.29, 95% confidence interval 1.02 to 1.64), although the heterogeneity between studies was high (P<0.0001). Pregnancy rates did not differ between women with an intention to conceive (two studies; 88% v 95%, 0.93, 0.80 to 1.08) and the number requiring more than 12 months to conceive (three studies, 15% v 9%, 1.45, 0.89 to 2.37). Although the rates for total miscarriages (10 studies; 4.6% v 2.8%, 1.04, 0.90 to 1.21) and miscarriage in the first trimester (four studies; 9.8% v 8.4%, 1.16, 0.80 to 1.69) was similar for treated and untreated women, cervical treatment was associated with a significantly increased risk of miscarriage in the second trimester. The rate was higher for treated women than for untreated women (eight studies; 1.6% v 0.4%, 16 558 women; 2.60, 1.45 to 4.67). The number of ectopic pregnancies (1.6% v 0.8%; 1.89, 1.50 to 2.39) and terminations (12.2% v 7.4%; 1.71, 1.31 to 2.22) was also higher for treated women. Conclusion There is no evidence suggesting that

  10. Acute coronary syndrome: a rare case of multiple endocrine neoplasia syndromes with pheochromocytoma and medullary thyroid carcinoma.

    PubMed

    Maloberti, Alessadro; Meani, Paolo; Pirola, Roberto; Varrenti, Marisa; Boniardi, Marco; De Biase, Anna Maria; Vallerio, Paola; Bonacina, Edgardo; Mancia, Giuseppe; Loli, Paola; Giannattasio, Cristina

    2015-09-01

    Pheochromocytoma is a tumor arising from neuroectodermal chromaffin tissues in the adrenal gland or extra-adrenal paraganglia (paragangliomas). The prevalence of the tumor is 0.1%-0.6% in the hypertensive population, of which 10%-20% are malignant. Pheochromocytoma produces, stores, and secretes catecholamines, as well as leads to hypertensive crisis, arrhythmia, angina, and acute myocardial infarction without coronary artery diseases. We report a case of acute coronary syndrome (ACS) with a final diagnosis of multiple endocrine neoplasia with pheochromocytoma and medullary thyroid carcinoma (MTC). PMID:26487970

  11. Acute coronary syndrome: a rare case of multiple endocrine neoplasia syndromes with pheochromocytoma and medullary thyroid carcinoma.

    PubMed

    Maloberti, Alessadro; Meani, Paolo; Pirola, Roberto; Varrenti, Marisa; Boniardi, Marco; De Biase, Anna Maria; Vallerio, Paola; Bonacina, Edgardo; Mancia, Giuseppe; Loli, Paola; Giannattasio, Cristina

    2015-09-01

    Pheochromocytoma is a tumor arising from neuroectodermal chromaffin tissues in the adrenal gland or extra-adrenal paraganglia (paragangliomas). The prevalence of the tumor is 0.1%-0.6% in the hypertensive population, of which 10%-20% are malignant. Pheochromocytoma produces, stores, and secretes catecholamines, as well as leads to hypertensive crisis, arrhythmia, angina, and acute myocardial infarction without coronary artery diseases. We report a case of acute coronary syndrome (ACS) with a final diagnosis of multiple endocrine neoplasia with pheochromocytoma and medullary thyroid carcinoma (MTC).

  12. Acute coronary syndrome: a rare case of multiple endocrine neoplasia syndromes with pheochromocytoma and medullary thyroid carcinoma

    PubMed Central

    Maloberti, Alessadro; Meani, Paolo; Pirola, Roberto; Varrenti, Marisa; Boniardi, Marco; De Biase, Anna Maria; Vallerio, Paola; Bonacina, Edgardo; Mancia, Giuseppe; Loli, Paola; Giannattasio, Cristina

    2015-01-01

    Pheochromocytoma is a tumor arising from neuroectodermal chromaffin tissues in the adrenal gland or extra-adrenal paraganglia (paragangliomas). The prevalence of the tumor is 0.1%-0.6% in the hypertensive population, of which 10%-20% are malignant. Pheochromocytoma produces, stores, and secretes catecholamines, as well as leads to hypertensive crisis, arrhythmia, angina, and acute myocardial infarction without coronary artery diseases. We report a case of acute coronary syndrome (ACS) with a final diagnosis of multiple endocrine neoplasia with pheochromocytoma and medullary thyroid carcinoma (MTC). PMID:26487970

  13. The transcriptional response to tumorigenic polarity loss in Drosophila.

    PubMed

    Bunker, Brandon D; Nellimoottil, Tittu T; Boileau, Ryan M; Classen, Anne K; Bilder, David

    2015-01-01

    Loss of polarity correlates with progression of epithelial cancers, but how plasma membrane misorganization drives oncogenic transcriptional events remains unclear. The polarity regulators of the Drosophila Scribble (Scrib) module are potent tumor suppressors and provide a model for mechanistic investigation. RNA profiling of Scrib mutant tumors reveals multiple signatures of neoplasia, including altered metabolism and dedifferentiation. Prominent among these is upregulation of cytokine-like Unpaired (Upd) ligands, which drive tumor overgrowth. We identified a polarity-responsive enhancer in upd3, which is activated in a coincident manner by both JNK-dependent Fos and aPKC-mediated Yki transcription. This enhancer, and Scrib mutant overgrowth in general, are also sensitive to activity of the Polycomb Group (PcG), suggesting that PcG attenuation upon polarity loss potentiates select targets for activation by JNK and Yki. Our results link epithelial organization to signaling and epigenetic regulators that control tissue repair programs, and provide insight into why epithelial polarity is tumor-suppressive.

  14. Synchronous clear cell renal cell carcinoma and multilocular cystic renal cell neoplasia of low malignant potential: A clinico-pathologic and molecular study.

    PubMed

    Raspollini, Maria Rosaria; Castiglione, Francesca; Cheng, Liang; Montironi, Rodolfo; Lopez-Beltran, Antonio

    2016-05-01

    We report a rare case of synchronous clear cell renal cell carcinoma and multilocular cystic renal cell neoplasia of low malignant potential in the same kidney. The tumors were seen incidentally in a 45-year-old man. Pathologic study revealed that the former tumor was nucleolar grade 2, and the multilocular cystic renal cell neoplasia of low malignant potential was nucleolar grade 1. At immunohistochemistry, the clear cells in both tumors were positive for CD10 and CA IX. Interestingly, these uncommon synchronous tumors showed a different KRAS/NRAS mutation analysis that was characterized by KRAS mutation at codon p.G12C in the clear cell renal cell carcinoma, while this mutation was not present in the case of multilocular cystic renal cell neoplasia of low malignant potential. NRAS mutation was not seen in any of the tumors. PMID:26874573

  15. Multiphoton microscopy, fluorescence lifetime imaging and optical spectroscopy for the diagnosis of neoplasia

    NASA Astrophysics Data System (ADS)

    Skala, Melissa Caroline

    2007-12-01

    Cancer morbidity and mortality is greatly reduced when the disease is diagnosed and treated early in its development. Tissue biopsies are the gold standard for cancer diagnosis, and an accurate diagnosis requires a biopsy from the malignant portion of an organ. Light, guided through a fiber optic probe, could be used to inspect regions of interest and provide real-time feedback to determine the optimal tissue site for biopsy. This approach could increase the diagnostic accuracy of current biopsy procedures. The studies in this thesis have characterized changes in tissue optical signals with carcinogenesis, increasing our understanding of the sensitivity of optical techniques for cancer detection. All in vivo studies were conducted on the dimethylbenz[alpha]anthracene treated hamster cheek pouch model of epithelial carcinogenesis. Multiphoton microscopy studies in the near infrared wavelength region quantified changes in tissue morphology and fluorescence with carcinogenesis in vivo. Statistically significant morphological changes with precancer included increased epithelial thickness, loss of stratification in the epithelium, and increased nuclear diameter. Fluorescence changes included a statistically significant decrease in the epithelial fluorescence intensity per voxel at 780 nm excitation, a decrease in the fluorescence lifetime of protein-bound nicotinamide adenine dinucleotide (NADH, an electron donor in oxidative phosphorylation), and an increase in the fluorescence lifetime of protein-bound flavin adenine dinucleotide (FAD, an electron acceptor in oxidative phosphorylation) with precancer. The redox ratio (fluorescence intensity of FAD/NADH, a measure of the cellular oxidation-reduction state) did not significantly change with precancer. Cell culture experiments (MCF10A cells) indicated that the decrease in protein-bound NADH with precancer could be due to increased levels of glycolysis. Point measurements of diffuse reflectance and fluorescence spectra in

  16. Single-nucleotide polymorphisms and haplotypes of membrane type 1-matrix metalloproteinase in susceptibility and clinical significance of squamous cell neoplasia of uterine cervix in Taiwan women.

    PubMed

    Tee, Yi-Torng; Liu, Yu-Fan; Chang, Jinghua Tsai; Yang, Shun-Fa; Chen, Shiuan-Chih; Han, Chih-Ping; Wang, Po-Hui; Liao, Chiung-Ling

    2012-09-01

    Membrane type 1-matrix metalloproteinase (MT1-MMP) participates in the activity of MMP-2, which correlates with cancer of uterine cervix. Single-nucleotide polymorphisms (SNPs) in promoter and exon of MT1-MMP may influence their binding with transcription factors and gene transcription. To date, no study reports the association of the MT1-MMP polymorphisms with cervical neoplasia. Therefore, we investigated the influence of the MT1-MMP gene polymorphisms on the susceptibility and clinicopathological variables of cervical neoplasia for women in Taiwan. We recruited 72 patients with cervical squamous cell carcinoma and 63 with high-grade dysplasia as 1 subgroup. Meanwhile, 280 control women were included as another subgroup. The SNPs rs1003349 (site -165), rs2236307 (+7096), and rs3751489 (+8153) as well as rs2236302 (site +6727) of MT1-MMP gene were determined by polymerase chain reaction (PCR)-restriction fragment length polymorphism and real-time PCR genotyping, respectively. Then, we correlated these SNPs and haplotypes with the development of cervical neoplasia and cancer clinicopathological variables. We found that women with CC genotype in rs2236307 SNP exhibited a more risk to develop cervical neoplasia as compared with those with wild genotype TT. Haplotypes -165 T, +6727 C, +7096 C, +8153 G or -165 G, +6727 G, +7096 T, and +8153 G and diplotypes including at least 1 type of these haplotypes of MT1-MMP gene showed a higher risk of cervical neoplasia. However, both haplotypes were not significantly correlated with the clinicopathological characteristics of cervical cancer. In conclusion, Taiwan women with variant homozygote CC (+7096) and haplotypes, TCCG and GGTG, of MT1-MMP exhibit more risk in developing cervical neoplasia.

  17. COMBINATION OF COMPUTED TOMOGRAPHIC IMAGING CHARACTERISTICS OF MEDIAL RETROPHARYNGEAL LYMPH NODES AND NASAL PASSAGES AIDS DISCRIMINATION BETWEEN RHINITIS AND NEOPLASIA IN CATS.

    PubMed

    Nemanic, Sarah; Hollars, Katelyn; Nelson, Nathan C; Bobe, Gerd

    2015-01-01

    Feline nasal diseases are a diagnostic challenge. The objective of this retrospective, cross-sectional study was to determine whether computed tomography (CT) imaging characteristics of the medial retropharyngeal lymph nodes (MRPLN), alone or in combination with CT imaging characteristics of the nasal passages, could aid in differentiation between rhinitis and nasal neoplasia. Cats were recruited from record archives at two veterinary facilities during the period of 2008-2012. Selection criteria were presentation for chronic nasal discharge, contrast-enhanced CT of the head that included the MRPLN, and rhinoscopic nasal biopsy resulting in diagnosis of rhinitis or neoplasia. For each CT scan, two board-certified veterinary radiologists recorded MRPLN size, attenuation, heterogeneity, contrast-medium enhancement, margination, shape, presence of a lymph node hilus, perinodal fat, turbinate lysis, paranasal bone lysis, and nasal mass. Both readers were unaware of patient information at the time of CT interpretation. Thirty-four cats with rhinitis and 22 cats with neoplasia were included. Computed tomographic characteristics significantly associated with neoplasia included abnormal MRPLN hilus (OR 5.1), paranasal bone lysis (OR 5.6), turbinate lysis (5.6), mass (OR 26.1), MRPLN height asymmetry (OR 4.5), and decreased MRPLN precontrast heterogeneity (OR 7.0). The combined features predictive of neoplasia were a nasal mass with abnormal hilus (OR 47.7); lysis of turbinates/paranasal bones with abnormal MRPLN hilus (OR 16.2). Findings supported the hypothesis that combining CT features of the nasal passages and MRPLN aided in differentiating rhinitis from neoplasia in cats. PMID:26194153

  18. COMBINATION OF COMPUTED TOMOGRAPHIC IMAGING CHARACTERISTICS OF MEDIAL RETROPHARYNGEAL LYMPH NODES AND NASAL PASSAGES AIDS DISCRIMINATION BETWEEN RHINITIS AND NEOPLASIA IN CATS.

    PubMed

    Nemanic, Sarah; Hollars, Katelyn; Nelson, Nathan C; Bobe, Gerd

    2015-01-01

    Feline nasal diseases are a diagnostic challenge. The objective of this retrospective, cross-sectional study was to determine whether computed tomography (CT) imaging characteristics of the medial retropharyngeal lymph nodes (MRPLN), alone or in combination with CT imaging characteristics of the nasal passages, could aid in differentiation between rhinitis and nasal neoplasia. Cats were recruited from record archives at two veterinary facilities during the period of 2008-2012. Selection criteria were presentation for chronic nasal discharge, contrast-enhanced CT of the head that included the MRPLN, and rhinoscopic nasal biopsy resulting in diagnosis of rhinitis or neoplasia. For each CT scan, two board-certified veterinary radiologists recorded MRPLN size, attenuation, heterogeneity, contrast-medium enhancement, margination, shape, presence of a lymph node hilus, perinodal fat, turbinate lysis, paranasal bone lysis, and nasal mass. Both readers were unaware of patient information at the time of CT interpretation. Thirty-four cats with rhinitis and 22 cats with neoplasia were included. Computed tomographic characteristics significantly associated with neoplasia included abnormal MRPLN hilus (OR 5.1), paranasal bone lysis (OR 5.6), turbinate lysis (5.6), mass (OR 26.1), MRPLN height asymmetry (OR 4.5), and decreased MRPLN precontrast heterogeneity (OR 7.0). The combined features predictive of neoplasia were a nasal mass with abnormal hilus (OR 47.7); lysis of turbinates/paranasal bones with abnormal MRPLN hilus (OR 16.2). Findings supported the hypothesis that combining CT features of the nasal passages and MRPLN aided in differentiating rhinitis from neoplasia in cats.

  19. Growth inhibition of Candida by human oral epithelial cells.

    PubMed

    Steele, C; Leigh, J; Swoboda, R; Fidel, P L

    2000-11-01

    Oropharyngeal candidiasis (OPC) caused by Candida albicans is a significant problem in human immunodeficiency virus (HIV)-infected persons. Recognizing the paucity of information on innate and/or adaptive mucosal host defenses against C. albicans, we recently reported that human and nonhuman primate and mouse vaginal epithelial cells inhibit the growth of C. albicans in vitro. In the present study, oral epithelial cells collected from saliva of healthy volunteers and a purified oral epithelial cell line were found to inhibit blastoconidia and/or hyphal growth of several Candida species. Cell contact was a strict requirement for the epithelial cell anti-Candida activity; neither saliva nor culture supernatants alone inhibited Candida growth, and addition of saliva to the coculture did not modulate the epithelial cell activity. Finally, epithelial cell anti-Candida activity was significantly lower in HIV-infected persons with OPC. Together, these results suggest that oral epithelial cells may play a role in innate resistance against OPC.

  20. Effect of Sulindac and Erlotinib vs Placebo on Duodenal Neoplasia in Familial Adenomatous Polyposis

    PubMed Central

    Samadder, N. Jewel; Neklason, Deborah W.; Boucher, Kenneth M.; Byrne, Kathryn R.; Kanth, Priyanka; Samowitz, Wade; Jones, David; Tavtigian, Sean V.; Done, Michelle W.; Berry, Therese; Jasperson, Kory; Pappas, Lisa; Smith, Laurel; Sample, Danielle; Davis, Rian; Topham, Matthew K.; Lynch, Patrick; Strait, Elena; McKinnon, Wendy; Burt, Randall W.; Kuwada, Scott K.

    2016-01-01

    IMPORTANCE Patients with familial adenomatous polyposis (FAP) are at markedly increased risk for duodenal polyps and cancer. Surgical and endoscopic management of duodenal neoplasia is difficult and chemoprevention has not been successful. OBJECTIVE To evaluate the effect of a combination of sulindac and erlotinib on duodenal adenoma regression in patients with FAP. DESIGN, SETTING, AND PARTICIPANTS Double-blind, randomized, placebo-controlled trial, enrolling 92 participants with FAP, conducted from July 2010 through June 2014 at Huntsman Cancer Institute in Salt Lake City, Utah. INTERVENTIONS Participants with FAP were randomized to sulindac (150 mg) twice daily and erlotinib (75 mg) daily (n = 46) vs placebo (n = 46) for 6 months. MAIN OUTCOMES AND MEASURES The total number and diameter of polyps in the proximal duodenum were mapped at baseline and 6 months. The primary outcome was change in total polyp burden at 6 months. Polyp burden was calculated as the sum of the diameters of polyps. The secondary outcomes were change in total duodenal polyp count, change in duodenal polyp burden or count stratified by genotype and initial polyp burden, and percentage of change from baseline in duodenal polyp burden. RESULTS Ninety-two participants (mean age, 41 years [range, 24–55]; women, 56 [61%]) were randomized when the trial was stopped by the external data and safety monitoring board because the second preplanned interim analysis met the prespecified stopping rule for superiority. Grade 1 and 2 adverse events were more common in the sulindac-erlotinib group, with an acne-like rash observed in 87% of participants receiving treatment and 20% of participants receiving placebo (P < .001). Only 2 participants experienced grade 3 adverse events. OutcomeBaseline6-moFollow-upMedianChangeBetween-GroupDifference (95% CI)PValueMedian Duodenal Polyp Burden, mmSulindac-erlotinib29.019.5−8.5−19.0 (−32.0 to −10.9)<.001Placebo23.031.08.0Median Duodenal Polyp Count, No

  1. Global acetylation and methylation changes predict papillary urothelial neoplasia of low malignant potential recurrence

    PubMed Central

    Mazzucchelli, R.; Scarpelli, M.; Lopez-Beltran, A.; Cheng, L.; Bartels, H.; Bartels, P. H.; Alberts, D. S.; Montironi, R.

    2014-01-01

    Papillary urothelial neoplasia of low malignant potential (PUNLMP) recurs in approximately 35% of patients. Conventional histopathological assessment does not distinguish non-recurrent from recurrent PUNLMP. The aim of the study was to explore the differences in global histone acetylation and global DNA methylation between non-recurrent and recurrent PUNLMP. Acetylated histone H3 lysine 9 (AcH3K9) and 5-methylcytosine (5MeC) were investigated by immunohistochemistry (IHC) in 20 PUNLMP cases (10 non-recurrent and 10 recurrent), in 5 cases of normal urothelium (NU) and in 5 cases of muscle invasive pT2 urothelial carcinoma (UC). The total optical density of the nuclear staining was measured photometrically in at least 40 nuclei separately for the basal, intermediate and luminal positions in each case. Concerning the total optical density values for both acetylation and methylation, a decrease in staining is observed from non-recurrent PUNLMP to recurrent PUNLMP, at all nuclear locations. For acetylation the mean value in non-recurrent. PUNLMP, intermediate between NU and UC, is closer to the former than to latter. The mean value in recurrent PUNLMP is closer to UC than to NU. In NU, non-recurrent and recurrent PUNLMP the acetylation to methylation ratio decreased from the nuclei in basal position to those in the surface, the average for the above groups being 1.491, 1.611 and 1.746, respectively. Setting the observed values for NU at each sampling location to unity, acetylation shows a steady decrease, the percentages of changes in this nuclear location compared to NU being − 5% in non-recurrent PUNLMP, − 15% in recurrent PUNLMP and − 24% in UC. Concerning methylation, there is slight increase in non-recurrent PUNLMP (+ 5%), a decrease in recurrent PUNLMP (− 19%) followed by a sharp rise for the UC (+ 61%). In conclusion there are differences in global histone acetylation and DNA methylation patterns between non-recurrent and recurrent PUNLMP. Further studies

  2. Depth-sensitive optical spectroscopy for noninvasive diagnosis of oral neoplasia

    NASA Astrophysics Data System (ADS)

    Schwarz, Richard Alan

    Oral cancer is the 11th most common cancer in the world. Cancers of the oral cavity and oropharynx account for more than 7,500 deaths each year in the United States alone. Major advances have been made in the management of oral cancer through the combined use of surgery, radiotherapy and chemotherapy, improving the quality of life for many patients; however, these advances have not led to a significant increase in survival rates, primarily because diagnosis often occurs at a late stage when treatment is more difficult and less successful. Accurate, objective, noninvasive methods for early diagnosis of oral neoplasia are needed. Here a method is presented to noninvasively evaluate oral lesions using depth-sensitive optical spectroscopy (DSOS). A ball lens coupled fiber-optic probe was developed to enable preferential targeting of different depth regions in the oral mucosa. Clinical studies of the diagnostic performance of DSOS in 157 subjects were carried out in collaboration with the University of Texas M. D. Anderson Cancer Center. An overall sensitivity of 90% and specificity of 89% were obtained for nonkeratinized oral tissue relative to histopathology. Based on these results a compact, portable version of the clinical DSOS device with real-time automated diagnostic capability was developed. The portable device was tested in 47 subjects and a sensitivity of 82% and specificity of 83% were obtained for nonkeratinized oral tissue. The diagnostic potential of multimodal platforms incorporating DSOS was explored through two pilot studies. A pilot study of DSOS in combination with widefield imaging was carried out in 29 oral cancer patients, resulting in a combined sensitivity of 94% and specificity of 69%. Widefield imaging and spectroscopy performed slightly better in combination than each method performed independently. A pilot study of DSOS in combination with the optical contrast agents 2-NBDG, EGF-Alexa 647, and proflavine was carried out in resected tissue

  3. Radiofrequency Ablation Versus Endoscopic Submucosal Dissection in Treating Large Early Esophageal Squamous Cell Neoplasia

    PubMed Central

    Wang, Wen-Lun; Chang, I-Wei; Chen, Chien-Chuan; Chang, Chi-Yang; Mo, Lein-Ray; Lin, Jaw-Town; Wang, Hsiu-Po; Lee, Ching-Tai

    2015-01-01

    Abstract Radiofrequency ablation (RFA) and endoscopic submucosal dissection (ESD) can potentially be applied for early esophageal squamous cell neoplasia (ESCN); however, no study has directly compared these 2 modalities. We retrospectively enrolled the patients with flat-type “large” (length ≥3 cm extending ≥1/2 of the circumference of esophagus) early ESCNs treated endoscopically. The main outcome measurements were complete response at 12 months, and adverse events. Of a total of 65 patients, 18 were treated with RFA and 47 with ESD. The procedure time of RFA was significantly shorter than that of ESD (126.6 vs 34.8 min; P < 0.001). The complete resection rate of ESD and complete response rate after primary RFA were 89.3% and 77.8%, respectively. Based on the histological evaluation of the post-ESD specimens showed 14 of 47 (29.8%) had histological upstaging compared with the pre-ESD biopsies, and 4 of them had lymphovascular invasion requiring chemoradiation or surgery. After additional therapy for residual lesions, 46 (97.9%) patients in the ESD group and 17 (94.4%) patients in the RFA group achieved a complete response at 12 months. Four patients (8.5%) developed major procedure-related adverse events in the ESD group, but none in the RFA group. In patients with lesions occupying more than 3/4 of the circumference, a significantly higher risk of esophageal stenosis was noted in the ESD group compared with RFA group (83% vs 27%, P = 0.01), which required more sessions of dilatation to resolve the symptoms (median, 13 vs 3, P = 0.04). There were no procedure-related mortality or neoplastic progression in either group; however, 1 patient who received ESD and 1 who received RFA developed local recurrence during a median follow-up period of 32.4 (range, 13–68) and 18.0 (range, 13–41) months, respectively. RFA and ESD are equally effective in the short-term treatment of early flat large ESCNs; however, more adverse events occur with ESD

  4. A Low-Cost HPV Immunochromatographic Assay to Detect High-Grade Cervical Intraepithelial Neoplasia

    PubMed Central

    Scapulatempo-Neto, Cristovam; Stein, Maíra Degiovani; Resende, Julio Cesar Possati; Antoniazzi, Márcio; Villa, Luisa Lina; Levi, José Eduardo; Longatto-Filho, Adhemar; Fregnani, José Humberto Tavares Guerreiro

    2016-01-01

    Objective To evaluate the reproducibility and accuracy of the HPV16/18-E6 test. Methods The study population was comprised of 448 women with a previously abnormal Pap who were referred to the Barretos Cancer Hospital (Brazil) for diagnosis and treatment. Two cervical samples were collected immediately before colposcopy, one for the hr-HPV-DNA test and cytology and the other for the HPV16/18-E6 test using high-affinity monoclonal antibodies (mAb). Women with a histologic diagnosis of cervical intraepithelial neoplasia grade 2 or 3 were considered to be positive cases. Different strategies using a combination of screening methods (HPV-DNA) and triage tests (cytology and HPV16/18-E6) were also examined and compared. Results The HPV16/18-E6 test exhibited a lower positivity rate compared with the HPV-DNA test (19.0% vs. 29.3%, p<0.001) and a moderate/high agreement (kappa = 0.68, 95%CI: 0.60–0.75). It also exhibited a significantly lower sensitivity for CIN2+ and CIN3+ detection compared to the HPV-DNA test and a significantly higher specificity. The HPV16/18-E6 test was no different from cytology in terms of sensitivity, but it exhibited a significantly higher specificity in comparison to ASCH+. A triage test after HPV-DNA detection using the HPV16/18-E6 test exhibited a significantly higher specificity compared with a triage test of ASCH+ to CIN2+ (91.8% vs. 87.4%, p = 0.04) and CIN3+ (88.6% vs. 84.0%, p = 0.05). Conclusion The HPV16/18-E6 test exhibited moderate/high agreement with the HPV-DNA test but lower sensitivity and higher specificity for the detection of CIN2+ and CIN3+. In addition, its performance was quite similar to cytology, but because of the structural design addressed for the detection of HPV16/18-E6 protein, the test can miss some CIN2/3+ lesions caused by other high-risk HPV types. PMID:27764154

  5. Induced pluripotency of human prostatic epithelial cells.

    PubMed

    Zhao, Hongjuan; Sun, Ning; Young, Sarah R; Nolley, Rosalie; Santos, Jennifer; Wu, Joseph C; Peehl, Donna M

    2013-01-01

    Induced pluripotent stem (iPS) cells are a valuable resource for discovery of epigenetic changes critical to cell type-specific differentiation. Although iPS cells have been generated from other terminally differentiated cells, the reprogramming of normal adult human basal prostatic epithelial (E-PZ) cells to a pluripotent state has not been reported. Here, we attempted to reprogram E-PZ cells by forced expression of Oct4, Sox2, c-Myc, and Klf4 using lentiviral vectors and obtained embryonic stem cell (ESC)-like colonies at a frequency of 0.01%. These E-PZ-iPS-like cells with normal karyotype gained expression of pluripotent genes typical of iPS cells (Tra-1-81, SSEA-3, Nanog, Sox2, and Oct4) and lost gene expression characteristic of basal prostatic epithelial cells (CK5, CK14, and p63). E-PZ-iPS-like cells demonstrated pluripotency by differentiating into ectodermal, mesodermal, and endodermal cells in vitro, although lack of teratoma formation in vivo and incomplete demethylation of pluripotency genes suggested only partial reprogramming. Importantly, E-PZ-iPS-like cells re-expressed basal epithelial cell markers (CD44, p63, MAO-A) in response to prostate-specific medium in spheroid culture. Androgen induced expression of androgen receptor (AR), and co-culture with rat urogenital sinus further induced expression of prostate-specific antigen (PSA), a hallmark of secretory cells, suggesting that E-PZ-iPS-like cells have the capacity to differentiate into prostatic basal and secretory epithelial cells. Finally, when injected into mice, E-PZ-iPS-like cells expressed basal epithelial cell markers including CD44 and p63. When co-injected with rat urogenital mesenchyme, E-PZ-iPS-like cells expressed AR and expression of p63 and CD44 was repressed. DNA methylation profiling identified epigenetic changes in key pathways and genes involved in prostatic differentiation as E-PZ-iPS-like cells converted to differentiated AR- and PSA-expressing cells. Our results suggest that

  6. Update on Sjögren's syndrome autoimmune epithelitis: from classification to increased neoplasias.

    PubMed

    Tzioufas, Athanasios G; Voulgarelis, Michael

    2007-12-01

    Sjögren's syndrome is a chronic inflammatory process that primarily involves the exocrine glands. Its clinical manifestations range from autoimmune exocrinopathy to extraglandular (systemic) involvement affecting the lungs, kidneys, blood vessels, and muscles; it can occur alone (primary Sjögren's syndrome) or in association with other autoimmune diseases (secondary Sjögren's syndrome). In recent years, clinical and laboratory observations have highlighted the central role of the epithelial cell and it has been suggested that the etiological name of the disease should be 'autoimmune epithelitis'. The extraglandular manifestations of the disease are divided in two groups: (1) lung, kidney (interstitial nephritis), and liver involvement as a result of lymphocytic invasion in epithelial tissues; and (2) skin vasculitis, peripheral neuropathy, and glomerulonephritis, with low C4 levels, which is the result of immune complex disease, are associated with increased morbidity and high risk for lymphoma. The diagnosis of the disease is based on the classification criteria, raised by the American-European Study Group and which have been built on the European preliminary classification criteria, developed in 1992. The association of Sjögren's syndrome with lymphoma is well documented as in approximately 5% of patients the benign autoimmune process is transformed into a lymphoid malignancy. The salivary extranodal marginal zone B-cell lymphomas of the mucosa-associated lymphoid tissue type are the most common lymphoma in Sjögren's syndrome. These tumors are antigen-stimulated B-cell lymphomas and are characterized by localized stage, indolent clinical course, and recurrence in other extranodal sites. Among the clinical and serological parameters that have been associated with lymphoma development in patients with Sjögren's syndrome, the presence of palpable purpura, low C4 and mixed monoclonal cryoglobulinemia constitute the main predictive markers; patients displaying

  7. Eukaryotic Translation Initiation Factor 4E Is a Feed-Forward Translational Coactivator of Transforming Growth Factor β Early Protransforming Events in Breast Epithelial Cells

    PubMed Central

    Decarlo, Lindsey; Mestel, Celine; Barcellos-Hoff, Mary-Helen

    2015-01-01

    Eukaryotic translation initiation factor 4E (eIF4E) is overexpressed early in breast cancers in association with disease progression and reduced survival. Much remains to be understood regarding the role of eIF4E in human cancer. We determined, using immortalized human breast epithelial cells, that elevated expression of eIF4E translationally activates the transforming growth factor β (TGF-β) pathway, promoting cell invasion, a loss of cell polarity, increased cell survival, and other hallmarks of early neoplasia. Overexpression of eIF4E is shown to facilitate the selective translation of integrin β1 mRNA, which drives the translationally controlled assembly of a TGF-β receptor signaling complex containing α3β1 integrins, β-catenin, TGF-β receptor I, E-cadherin, and phosphorylated Smad2/3. This receptor complex acutely sensitizes nonmalignant breast epithelial cells to activation by typically substimulatory levels of activated TGF-β. TGF-β can promote cellular differentiation or invasion and transformation. As a translational coactivator of TGF-β, eIF4E confers selective mRNA translation, reprogramming nonmalignant cells to an invasive phenotype by reducing the set point for stimulation by activated TGF-β. Overexpression of eIF4E may be a proinvasive facilitator of TGF-β activity. PMID:25986608

  8. Eukaryotic Translation Initiation Factor 4E Is a Feed-Forward Translational Coactivator of Transforming Growth Factor β Early Protransforming Events in Breast Epithelial Cells.

    PubMed

    Decarlo, Lindsey; Mestel, Celine; Barcellos-Hoff, Mary-Helen; Schneider, Robert J

    2015-08-01

    Eukaryotic translation initiation factor 4E (eIF4E) is overexpressed early in breast cancers in association with disease progression and reduced survival. Much remains to be understood regarding the role of eIF4E in human cancer. We determined, using immortalized human breast epithelial cells, that elevated expression of eIF4E translationally activates the transforming growth factor β (TGF-β) pathway, promoting cell invasion, a loss of cell polarity, increased cell survival, and other hallmarks of early neoplasia. Overexpression of eIF4E is shown to facilitate the selective translation of integrin β1 mRNA, which drives the translationally controlled assembly of a TGF-β receptor signaling complex containing α3β1 integrins, β-catenin, TGF-β receptor I, E-cadherin, and phosphorylated Smad2/3. This receptor complex acutely sensitizes nonmalignant breast epithelial cells to activation by typically substimulatory levels of activated TGF-β. TGF-β can promote cellular differentiation or invasion and transformation. As a translational coactivator of TGF-β, eIF4E confers selective mRNA translation, reprogramming nonmalignant cells to an invasive phenotype by reducing the set point for stimulation by activated TGF-β. Overexpression of eIF4E may be a proinvasive facilitator of TGF-β activity.

  9. Expression analysis of Matrix Metalloproteinase-9 in epithelialized and non-epithelialized apical periodontitis lesions

    PubMed Central

    Carneiro, Everdan; Menezes, Renato; Garlet, Gustavo Pompermaier; Garcia, Roberto Brandão; Bramante, Clóvis Monteiro; Figueira, Rita; Sogayar, Mari; Granjeiro, José Mauro

    2009-01-01

    OBJECTIVE To determine the expression of matrix metalloproteinase-9 (MMP-9) in apical periodontitis lesions. STUDY DESIGN Nineteen epithelialized and eighteen non-epithelialized apical periodontitis lesions were collected after periapical surgery. After histological processing, serial sectioning, H&E staining and microscopic analysis, 10 epithelialized and 10 non-epithelialized lesions were selected for immunohistochemical analysis for MMP-9 and CD 68. At least 1/3 of each specimen was frozen at −70°C for further mRNA isolation and reverse transcription into cDNA for Real-Time-PCR procedures. The relative expression of a target gene was determined in comparison with reference genes (GAPDH, HPRT, β-actin and BCRP). RESULTS Polymorphonuclear neutrophils, macrophages and lymphocytes were stained for MMP-9 in both types of lesions, and when present, epithelial cells were also stained. The number and the ratio of MMP-9+/total cells were greater in non-epithelialized than epithelialized lesions (p=0.0001) and showed a positive correlation to CD68+/total cells (p=0.045). No significant differences were observed for MMP-9 mRNA expression between ephithelized and non-ephithelized lesions. However, when compared to healthy periapical ligaments, both types of lesions presented increased MMP-9 expression (p<0.0001). CONCLUSION The present data suggest the participation of several inflammatory cells, mainlly CD68+ cells, in the MMP-9 expression in apical periodontitis lesions. MMP-9 could be actively enroled in the ECM degradation in apical periodontitis lesions. PMID:18926740

  10. Clinical application of magnification endoscopy and narrow-band imaging in the upper gastrointestinal tract: new imaging techniques for detecting and characterizing gastrointestinal neoplasia.

    PubMed

    Yao, Kenshi; Takaki, Yasuhiro; Matsui, Toshiyuki; Iwashita, Akinori; Anagnostopoulos, George K; Kaye, Philip; Ragunath, Krish

    2008-07-01

    This article introduces one of the most advanced endoscopy imaging techniques, magnification endoscopy with narrow-band imaging. This technique can clearly visualize the microvascular (MV) architecture and microsurface (MS) structure. The application of this technique is quite useful for characterizing the mucosal neoplasia in the hypopharynx, oropharynx, esophagus, and stomach. The key characteristic findings for early carcinomatous lesions are an irregular MV pattern or irregular MS pattern as visualized by this technique. Such a diagnostic system could be applied to the early detection of mucosal neoplasia throughout the upper gastrointestinal tract.

  11. Parathyroid gland-specific deletion of the mouse Men1 gene results in parathyroid neoplasia and hypercalcemic hyperparathyroidism.

    PubMed

    Libutti, Steven K; Crabtree, Judy S; Lorang, Dominique; Burns, A Lee; Mazzanti, Chiara; Hewitt, Stephen M; O'Connor, Sarah; Ward, Jerrold M; Emmert-Buck, Michael R; Remaley, Alan; Miller, Marshall; Turner, Ewa; Alexander, H Richard; Arnold, Andrew; Marx, Stephen J; Collins, Francis S; Spiegel, Allen M

    2003-11-15

    The inactivation of the MEN1 tumor suppressor gene in patients leads to a constellation of changes in endocrine tissues, including parathyroid neoplasia, pituitary adenomas, pancreatic neuroendocrine tumors, and carcinoids. To study the pathophysiological consequences of the deletion of the MEN1 gene, we set out to create a mouse model of hyperparathyroidism resulting from the deletion of the Men1 gene in parathyroid tissue. We introduced a Men1 gene flanked by loxP sites into the mouse germ line and then used a parathyroid cell-specific promoter to drive the expression of Cre recombinase, resulting in the deletion of the Men1 gene. Here, we show that loss of Men1 gene function in the parathyroid glands of mice results in histological changes consistent with parathyroid neoplasia as well as systemic hypercalcemia. This model provides a means for dissecting the molecular basis of this familial cancer syndrome and may allow for the development of new strategies to treat related forms of hypercalcemia.

  12. Genetic predisposition to peripheral nerve neoplasia: diagnostic criteria and pathogenesis of neurofibromatoses, Carney complex, and related syndromes.

    PubMed

    Rodriguez, Fausto J; Stratakis, Constantine A; Evans, D Gareth

    2012-03-01

    Neoplasms of the peripheral nerve sheath represent essential clinical manifestations of the syndromes known as the neurofibromatoses. Although involvement of multiple organ systems, including skin, central nervous system, and skeleton, may also be conspicuous, peripheral nerve neoplasia is often the most important and frequent cause of morbidity in these patients. Clinical characteristics of neurofibromatosis type 1 (NF1) and neurofibromatosis type 2 (NF2) have been extensively described and studied during the last century, and the identification of mutations in the NF1 and NF2 genes by contemporary molecular techniques have created a separate multidisciplinary field in genetic medicine. In schwannomatosis, the most recent addition to the neurofibromatosis group, peripheral nervous system involvement is the exclusive (or almost exclusive) clinical manifestation. Although the majority of cases of schwannomatosis are sporadic, approximately one-third occur in families and a subset of these has recently been associated with germline mutations in the tumor suppressor gene SMARCB1/INI1. Other curious syndromes that involve the peripheral nervous system are associated with predominant endocrine manifestations, and include Carney complex and MEN2b, secondary to inactivating mutations in the PRKAR1A gene in a subset, and activating mutations in RET, respectively. In this review, we provide a concise update on the diagnostic criteria, pathology and molecular pathogenesis of these enigmatic syndromes in relation to peripheral nerve sheath neoplasia. PMID:22210082

  13. Identification of Human Herpesvirus 8 Sequences in Conjunctiva Intraepithelial Neoplasia and Squamous Cell Carcinoma of Ugandan Patients

    PubMed Central

    Starita, Noemy; Annunziata, Clorinda; Waddell, Keith M.; Buonaguro, Luigi; Buonaguro, Franco M.; Tornesello, Maria Lina

    2015-01-01

    The incidence of squamous cell carcinoma of the conjunctiva is particularly high in sub-Saharan Africa with temporal trends similar to those of Kaposi sarcoma (KS). Human herpesvirus type 8 (HHV8), has not yet been investigated in conjunctiva tumors. In this study biopsies and PBMCs of conjunctiva neoplasia patients along with nonneoplastic conjunctiva tissues have been analyzed for HHV8 sequences by PCR targeting ORF26. All amplimers were subjected to nucleotide sequencing followed by phylogenetic analysis. HHV8 DNA has been identified in 12 out of 48 (25%) HIV-positive, and in 2 out of 24 (8.3%) HIV-negative conjunctiva neoplastic tissues and in 4 out of 33 (12.1%) PBMC samples from conjunctiva neoplasia diseased patients as well as in 4 out of 60 (6.7%) nontumor conjunctiva tissues. The viral load ranged from 1 to 400 copies/105 cells. Phylogenetic analysis showed that the majority of HHV8 ORF26 amplimers clustered with subtypes R (n = 11) and B2 (n = 6). This variant distribution is in agreement with that of HHV8 variants previously identified in Ugandan KS cases. The presence of HHV8 in conjunctiva tumors from HIV-positive patients warrants further studies to test whether HHV8 products released by infected cells may have paracrine effects on the growth of conjunctiva lesions. PMID:26509162

  14. Growth of corneal epithelial cells over in situ therapeutic contact lens after simple limbal epithelial transplantation (SLET)

    PubMed Central

    Bhalekar, Swapnil; Sangwan, Virender S; Basu, Sayan

    2013-01-01

    An 11-year-old boy underwent simple limbal epithelial transplantation (SLET) from the healthy right eye to his left eye for total limbal stem cell deficiency. One month later, corneal surface epithelialised and whitish plaques overlying the transplants were seen inferiorly. Those plaques were adherent to the surface of the contact lens and underlying corneal surface had smooth elevations. Similar findings were noted in a 23-year man following cyanoacrylate glue application for corneal perforation. On histological and immunohistochemical analysis, cells lining the contact lenses were identified as corneal epithelial cells. These cases illustrate epithelial cell growth on the contact lens and epithelial hyperplasia on corresponding surface of the cornea. Exorbitant proliferation of the epithelial cells may be owing to young age; therefore, early contact lens removal after SLET in young age, can possibly avoid epithelial hyperplasia. This also reiterates the possibility of using contact lens as a scaffold to grow epithelial cells. PMID:23814196

  15. Epithelial to Stromal Re-Distribution of Primary Cilia during Pancreatic Carcinogenesis

    PubMed Central

    Schimmack, Simon; Kneller, Sarah; Dadabaeva, Nigora; Bergmann, Frank; Taylor, Andrew; Hackert, Thilo; Werner, Jens; Strobel, Oliver

    2016-01-01

    Background The Hedgehog (HH) pathway is a mediator in pancreatic ductal adenocarcinoma (PDAC). Surprisingly, previous studies suggested that primary cilia (PC), the essential organelles for HH signal transduction, were lost in PDAC. The aim of this study was to determine the presence of PC in human normal pancreas, chronic pancreatitis, and during carcinogenesis to PDAC with focus on both epithelia and stroma. Methods PC were analyzed in paraffin sections from normal pancreas, chronic pancreatitis, intraductal papillary-mucinous neoplasia, and PDAC, as well as in primary human pancreatic stellate cells (PSC) and pancreatic cancer cell lines by double immunofluorescence staining for acetylated α-tubuline and γ-tubuline. Co-staining for the HH receptors PTCH1, PTCH2 and SMO was also performed. Results PC are gradually lost during pancreatic carcinogenesis in the epithelium: the fraction of cells with PC gradually and significantly decreased from 32% in ducts of normal pancreas, to 21% in ducts of chronic pancreatitis, to 18% in PanIN1a, 6% in PanIN2, 3% in PanIN3 and to 1.2% in invasive PDAC. However, this loss of PC in the neoplastic epithelium is accompanied by a gain of PC in the surrounding stroma. The fraction of stromal cells with PC significantly increased from 13% around normal ducts to about 30% around PanIN and PDAC. HH-receptors were detected in tumor stroma but not in epithelial cells. PC are also present in PSC and pancreatic cancer cell lines. Conclusion PC are not lost during pancreatic carcinogenesis but re-distributed from the epithelium to the stroma. This redistribution may explain the re-direction of HH signaling towards the stroma during pancreatic carcinogenesis. PMID:27783689

  16. Lack of Cyclin-Dependent Kinase 4 Inhibits c-myc Tumorigenic Activities in Epithelial Tissues

    PubMed Central

    Miliani de Marval, Paula L.; Macias, Everardo; Rounbehler, Robert; Sicinski, Piotr; Kiyokawa, Hiroaki; Johnson, David G.; Conti, Claudio J.; Rodriguez-Puebla, Marcelo L.

    2004-01-01

    The proto-oncogene c-myc encodes a transcription factor that is implicated in the regulation of cellular proliferation, differentiation, and apoptosis and that has also been found to be deregulated in several forms of human and experimental tumors. We have shown that forced expression of c-myc in epithelial tissues of transgenic mice (K5-Myc) resulted in keratinocyte hyperproliferation and the development of spontaneous tumors in the skin and oral cavity. Although a number of genes involved in cancer development are regulated by c-myc, the actual mechanisms leading to Myc-induced neoplasia are not known. Among the genes regulated by Myc is the cyclin-dependent kinase 4 (CDK4) gene. Interestingly, previous studies from our laboratory showed that the overexpression of CDK4 led to keratinocyte hyperproliferation, although no spontaneous tumor development was observed. Thus, we tested the hypothesis that CDK4 may be one of the critical downstream genes involved in Myc carcinogenesis. Our results showed that CDK4 inhibition in K5-Myc transgenic mice resulted in the complete inhibition of tumor development, suggesting that CDK4 is a critical mediator of tumor formation induced by deregulated Myc. Furthermore, a lack of CDK4 expression resulted in marked decreases in epidermal thickness and keratinocyte proliferation compared to the results obtained for K5-Myc littermates. Biochemical analysis of the K5-Myc epidermis showed that CDK4 mediates the proliferative activities of Myc by sequestering p21Cip1 and p27Kip1 and thereby indirectly activating CDK2 kinase activity. These results show that CDK4 mediates the proliferative and oncogenic activities of Myc in vivo through a mechanism that involves the sequestration of specific CDK inhibitors. PMID:15314163

  17. Retinal pigment epithelial change and partial lipodystrophy.

    PubMed Central

    Davis, T. M.; Holdright, D. R.; Schulenberg, W. E.; Turner, R. C.; Joplin, G. F.

    1988-01-01

    Cuticular drusen and retinal pigment epithelial changes were found incidentally in a 27 year old Lebanese woman during assessment of partial lipodystrophy. Her vision was normal despite involvement of both maculae. The patient had hypocomplementaemia, but serum C3 nephritic factor was absent and renal function was normal. She had impaired glucose tolerance and a continuous infusion of glucose with model assessment (CIGMA) test revealed low normal tissue insulin sensitivity and high normal pancreatic beta cell function. Mild fasting hypertriglyceridaemia (2.0 mmol/l) may have been secondary to impaired insulin sensitivity. Endocrine function was otherwise normal apart from a completely absent growth hormone response to adequate hypoglycaemia. The simultaneous occurrence of partial lipodystrophy and retinal pigmentary epithelial and basement membrane changes appears to be a newly recognized syndrome. Images Figure 1 Figure 2 PMID:3255937

  18. Epithelial Proliferation on Curved Toroidal Surfaces

    NASA Astrophysics Data System (ADS)

    Chang, Ya-Wen; Cruz, Ricardo; Fragkopoulos, Alexandros; Marquez, Samantha; Garcia, Andres; Fernandez-Nieves, Alberto

    Cellular environment influences a multitude of cellular functions by providing chemical and physical signals that modulate cell behavior, dynamics, development, and eventually survival. In strongly interacting epithelial cells, cells coordinate their behavior to respond to mechanical constraints in 2D. Local differences in tissue tension has also been shown to impact cell reproduction within an epithelial-cell sheet. Much less is known about how cells respond to out-of-plane curvatures. Here, we describe the proliferation of MDCK on toroidal hydrogel substrates, which unlike spheres or planes, have regions of both positive and negative Gaussian curvature. Additionally, the range of curvatures can be controlled by varying the size and aspect ratio of the torus, allowing us to quantify the relation between substrate curvature and cell proliferation.

  19. Extensive Focal Epithelial Hyperplasia: A Case Report

    PubMed Central

    Mansouri, Zahra; Bakhtiari, Sedigheh; Noormohamadi, Robab

    2015-01-01

    Focal epithelial hyperplasia (FEH) or Heck’s disease is a rare viral infection of the oral mucosa caused by human papilloma virus especially subtypes 13 or 32. The frequency of this disease varies widely from one geographic region and ethnic groups to another. This paper reports an Iranian case of extensive focal epithelial hyperplasia. A 35-year-old man with FEH is described, in whom the lesions had persisted for more than 25 years. The lesion was diagnosed according to both clinical and histopathological features. Dental practitioner should be aware of these types of lesions and histopathological examination together and a careful clinical observation should be carried out for a definitive diagnosis. PMID:26351501

  20. Ontogeny of Intestinal Epithelial Innate Immune Responses

    PubMed Central

    Hornef, Mathias W.; Fulde, Marcus

    2014-01-01

    Emerging evidence indicates that processes during postnatal development might significantly influence the establishment of mucosal host-microbial homeostasis. Developmental and adaptive immunological processes but also environmental and microbial exposure early after birth might thus affect disease susceptibility and health during adult life. The present review aims at summarizing the current understanding of the intestinal epithelial innate immune system and its developmental and adaptive changes after birth. PMID:25346729

  1. [Focal epithelial hyperplasia in lepromatous leprosy].

    PubMed

    Jacyk, W; Lechner, W

    1983-10-15

    Focal epithelial hyperplasia Heck (FEH) is most likely caused by human papilloma virus. It mainly occurs in children and young people showing no associated diseases. For the first time, we describe a case of FEH in a patient with lepromatous leprosy who due to persistent erythema nodosum leprosum has been treated with a lang-term glucocorticoid therapy. The question of the competence of lepromatous patients in resisting certain viral infections arises.

  2. Focal epithelial hyperplasia in a Turkish family.

    PubMed

    Gökahmetoğlu, Selma; Ferahbaş, Ayten; Canöz, Özlem

    2014-12-01

    Focal epithelial hyperplasia (FEH) is a benign proliferative condition that is more frequently found in children of certain ethnic groups. Human papillomavirus (HPV) 13 and 32 genotypes has been consistently detected in these lesions. In this study a daughter, mother and father had FEH, and HPV 13 was shown by sequence analysis in the lesions of these patients. Cryotherapy was applied to the lesions and the lesions improved, but did not recover properly. In conclusion, HPV genotyping should be performed in FEH cases.

  3. Extensive focal epithelial hyperplasia: case report.

    PubMed

    Durso, Braz Campos; Pinto, José Marcelo Vargas; Jorge, Jacks; de Almeida, Oslei Paes

    2005-11-01

    Focal epithelial hyperplasia (FEH) is a rare benign lesion caused by human papillomavirus subtype 13 or 32. The condition occurs in numerous populations and ethnic groups. A higher incidence in close communities and among family members indicates infectious pathogenesis. A 21-year-old woman with FEH is described, in whom the lesions had persisted for 10 years. A literature review is also presented, with emphasis on manifestations in the oral mucosa and histopathological features.

  4. Fibro-epithelial hyperplasia mimicking mucocele.

    PubMed

    Jain, K; Singh, B D; Dubey, A; Avinash, A

    2014-01-01

    The effects of chronic local irritation have been seen commonly in the form of fibroma or mucocele in children. We report a ten year old girl with the chief complaint of swelling in the lower right region of labial mucosa which was diagnosed clinically as mucocele and histologically as fibro-epithelial hyperplasia. Surgical excision was done under local anesthesia with no post-operative complication. PMID:25552222

  5. CUX1/Wnt signaling regulates Epithelial Mesenchymal Transition in EBV infected epithelial cells

    SciTech Connect

    Malizia, Andrea P.; Lacey, Noreen; Walls, Dermot; Egan, Jim J.; Doran, Peter P.

    2009-07-01

    Idiopathic pulmonary fibrosis (IPF) is a refractory and lethal interstitial lung disease characterized by alveolar epithelial cells apoptosis, fibroblast proliferation and extra-cellular matrix protein deposition. EBV, localised to alveolar epithelial cells of pulmonary fibrosis patients is associated with a poor prognosis. A strategy based on microarray-differential gene expression analysis to identify molecular drivers of EBV-associated lung fibrosis was utilized. Alveolar epithelial cells were infected with EBV to identify genes whose expression was altered following TGF{beta}1-mediated lytic phase. EBV lytic reactivation by TGF{beta}1 drives a selective alteration in CUX1 variant (a) (NCBI accession number NM{sub 1}81552) expression, inducing activation of non-canonical Wnt pathway mediators, implicating it in Epithelial Mesenchymal Transition (EMT), the molecular event underpinning scar production in tissue fibrosis. The role of EBV in EMT can be attenuated by antiviral strategies and inhibition of Wnt signaling by using All-Trans Retinoic Acids (ATRA). Activation of non-canonical Wnt signaling pathway by EBV in epithelial cells suggests a novel mechanism of EMT via CUX1 signaling. These data present a framework for further description of the link between infectious agents and fibrosis, a significant disease burden.

  6. Characteristics and pharmacological regulation of epithelial Na+ channel (ENaC) and epithelial Na+ transport.

    PubMed

    Marunaka, Yoshinori

    2014-01-01

    Epithelial Na(+) transport participates in control of various body functions and conditions: e.g., homeostasis of body fluid content influencing blood pressure, control of amounts of fluids covering the apical surface of alveolar epithelial cells at appropriate levels for normal gas exchange, and prevention of bacterial/viral infection. Epithelial Na(+) transport via the transcellular pathway is mediated by the entry step of Na(+) across the apical membrane via Epithelial Na(+) Channel (ENaC) located at the apical membrane, and the extrusion step of Na(+) across the basolateral membrane via the Na(+),K(+)-ATPase located at the basolateral membrane. The rate-limiting step of the epithelial Na(+) transport via the transcellular pathway is generally recognized to be the entry step of Na(+) across the apical membrane via ENaC. Thus, up-/down-regulation of ENaC essentially participates in regulatory systems of blood pressure and normal gas exchange. Amount of ENaC-mediated Na(+) transport is determined by the number of ENaCs located at the apical membrane, activity (open probability) of individual ENaC located at the apical membrane, single channel conductance of ENaC located at the apical membrane, and driving force for the Na(+) entry via ENaCs across the apical membrane. In the present review article, I discuss the characteristics of ENaC and how these factors are regulated.

  7. Epithelial-mesenchymal, mesenchymal-epithelial, and endothelial-mesenchymal transitions in malignant tumors: An update

    PubMed Central

    Gurzu, Simona; Turdean, Sabin; Kovecsi, Attila; Contac, Anca Otilia; Jung, Ioan

    2015-01-01

    Epithelial-to-mesenchymal transition (EMT) represents conversion of an epithelial cell in an elongated cell with mesenchymal phenotype, which can occur in physiologic and pathologic processes such as embryogenesis (type 1 EMT), wound healing and/or fibrosis (type 2 EMT) and malignant tumors (type 3 EMT). The proliferation rate, metastasizing and recurrence capacity, as also the individualized response at chemotherapics, in both epithelial and mesenchymal malignant tumors is known to be influenced by reversible switch between EMT and mesenchymal-to-epithelial transition (MET). Although much research work has already been done in these fields, the specific molecular pathways of EMT, relating to the tumor type and tumor localization, are yet to be elucidated. In this paper, based on the literature and personal experience of the authors, an update in the field of EMT vs MET in epithelial and mesenchymal tumors is presented. The authors tried to present the latest data about the particularities of these processes, and also of the so-called endothelial-to-mesenchymal transition, based on tumor location. The EMT-angiogenesis link is discussed as a possible valuable parameter for clinical follow-up and targeted therapeutic oncologic management. The paper begins with presentation of the basic aspects of EMT, its classification and assessment possibilities, and concludes with prognostic and therapeutic perspectives. The particularities of EMT and MET in gastric and colorectal carcinomas, pancreatic cancer, hepatocellular and cholangiocarcinomas, and lung, breast and prostate cancers, respectively in sarcomas and gastrointestinal stromal tumors are presented in detail. PMID:25984514

  8. Epithelial cysts of the spleen: a minireview.

    PubMed

    Ingle, Sachin B; Hinge Ingle, Chitra R; Patrike, Swapna

    2014-10-14

    Primary splenic epithelial cyst is an unusual event in everyday surgical practice with about 800 cases reported until date in the English literature. Splenic cysts may be parasitic or non-parasitic in origin. Nonparasitic cysts are either primary or secondary. Primary cysts are also called true, congenital, epidermoid or epithelial cysts. Primary splenic cysts account for 10% of all benign non-parasitic splenic cysts and are the most frequent type of splenic cysts in children. Usually, splenic cysts are asymptomatic and can be found incidentally during imaging techniques or on laparotomy. The symptoms are related to the size of cysts. When they assume large sizes, they may present with fullness in the left abdomen, local or referred pain, symptoms due to compression of adjacent structures (like nausea, vomiting, flatulence, diarrhoea) or rarely thrombocytopenia, and occasionally complications such as infection, rupture and/or haemorrhage. The preoperative diagnosis of primary splenic cysts can be ascertained by ultrasonography (USG), computed tomography or magnetic resonance imaging, although the wide use of USG today has led to an increase in the incidence of splenic cysts by 1%. However, careful histopathological evaluation along with immunostaining for presence of epithelial lining is mandatory to arrive at the diagnosis. The treatment has changed drastically from total splenectomy in the past to splenic preservation methods recently.

  9. Mayo Clinic experience with epithelial ovarian cancer.

    PubMed

    Decker, D G

    1983-08-01

    Clinical investigation of epithelial ovarian cancer must involve the precise definition of the lesion, careful application of new techniques, the objective evaluation of such techniques, the comparison of results in a randomized fashion with prior forms of therapy, careful pathological evaluation of the tumour, and the evaluation of toxicity to the patient. The interdisciplinary team approach to the treatment of epithelial ovarian cancer and the development of randomized, prospective trials are essential. Utilizing these two elements, a better integration of surgery, chemotherapy and radiation therapy can be accomplished. Of great importance is the evaluation of response patterns by an observer who is skilled in pelvic examinations and familiar with the natural history of epithelial ovarian cancer. The increasingly important role of surgery in the treatment of this cancer is now more clearly defined. The psychological effects of chemotherapy as well as the response patterns to chemotherapy must be evaluated. During the past 20 years, considerable progress has been made in prolonging the useful, functional life of the patient. The ultimate cure is still a matter for the future and is predicated on more effective combinations of potent chemotherapeutic combinations and a clearer definition of the role of radiation therapy.

  10. Protein complexes that control renal epithelial polarity

    PubMed Central

    Pieczynski, Jay

    2011-01-01

    Establishment of epithelial apicobasal polarity is crucial for proper kidney development and function. In recent years, there have been important advances in our understanding of the factors that mediate the initiation of apicobasal polarization. Key among these are the polarity complexes that are evolutionarily conserved from simple organisms to humans. Three of these complexes are discussed in this review: the Crumbs complex, the Par complex, and the Scribble complex. The apical Crumbs complex consists of three proteins, Crumbs, PALS1, and PATJ, whereas the apical Par complex consists of Par-3, Par-6, and atypical protein kinase C. The lateral Scribble complex consists of Scribble, discs large, and lethal giant larvae. These complexes modulate kinase and small G protein activity such that the apical and basolateral complexes signal antagonistically, leading to the segregation of the apical and basolateral membranes. The polarity complexes also serve as scaffolds to direct and retain proteins at the apical membrane, the basolateral membrane, or the intervening tight junction. There is plasticity in apicobasal polarity, and this is best seen in the processes of epithelial-to-mesenchymal transition and the converse mesenchymal-to-epithelial transition. These transitions are important in kidney disease as well as kidney development, and modulation of the polarity complexes are critical for these transitions. PMID:21228104

  11. Gasotransmitters: novel regulators of epithelial na(+) transport?

    PubMed

    Althaus, Mike

    2012-01-01

    The vectorial transport of Na(+) across epithelia is crucial for the maintenance of Na(+) and water homeostasis in organs such as the kidneys, lung, or intestine. Dysregulated Na(+) transport processes are associated with various human diseases such as hypertension, the salt-wasting syndrome pseudohypoaldosteronism type 1, pulmonary edema, cystic fibrosis, or intestinal disorders, which indicate that a precise regulation of epithelial Na(+) transport is essential. Novel regulatory signaling molecules are gasotransmitters. There are currently three known gasotransmitters: nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H(2)S). These molecules are endogenously produced in mammalian cells by specific enzymes and have been shown to regulate various physiological processes. There is a growing body of evidence which indicates that gasotransmitters may also regulate Na(+) transport across epithelia. This review will summarize the available data concerning NO, CO, and H(2)S dependent regulation of epithelial Na(+) transport processes and will discuss whether or not these mediators can be considered as true physiological regulators of epithelial Na(+) transport biology.

  12. Replication of cultured lung epithelial cells

    SciTech Connect

    Guzowski, D.; Bienkowski, R.

    1986-03-05

    The authors have investigated the conditions necessary to support replication of lung type 2 epithelial cells in culture. Cells were isolated from mature fetal rabbit lungs (29d gestation) and cultured on feeder layers of mitotically inactivated 3T3 fibroblasts. The epithelial nature of the cells was demonstrated by indirect immunofluorescent staining for keratin and by polyacid dichrome stain. Ultrastructural examination during the first week showed that the cells contained myofilaments, microvilli and lamellar bodies (markers for type 2 cells). The following changes were observed after the first week: increase in cell size; loss of lamellar bodies and appearance of multivesicular bodies; increase in rough endoplasmic reticulum and golgi; increase in tonafilaments and well-defined junctions. General cell morphology was good for up to 10 wk. Cells cultured on plastic surface degenerated after 1 wk. Cell replication was assayed by autoradiography of cultures exposed to (/sup 3/H)-thymidine and by direct cell counts. The cells did not replicate during the first week; however, between 2-10 wk the cells incorporated the label and went through approximately 6 population doublings. They have demonstrated that lung alveolar epithelial cells can replicate in culture if they are maintained on an appropriate substrate. The coincidence of ability to replicate and loss of markers for differentiation may reflect the dichotomy between growth and differentiation commonly observed in developing systems.

  13. Colonic epithelial ion transport is not affected in patients with diverticulosis

    PubMed Central

    Osbak, Philip S; Bindslev, Niels; Poulsen, Steen S; Kaltoft, Nicolai; Tilotta, Maria C; Hansen, Mark B

    2007-01-01

    Background Colonic diverticular disease is a bothersome condition with an unresolved pathogenesis. It is unknown whether a neuroepithelial dysfunction is present. The aim of the study was two-fold; (1) to investigate colonic epithelial ion transport in patients with diverticulosis and (2) to adapt a miniaturized Modified Ussing Air-Suction (MUAS) chamber for colonic endoscopic biopsies. Methods Biopsies were obtained from the sigmoid part of the colon. 86 patients were included. All patients were referred for colonoscopy on suspicion of neoplasia and they were without pathological findings at colonoscopy (controls) except for diverticulosis in 22 (D-patients). Biopsies were mounted in MUAS chambers with an exposed area of 5 mm2. Electrical responses to various stimu