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Sample records for jnk-dependent epithelial neoplasia

  1. Pseudomonas aeruginosa-induced apoptosis in airway epithelial cells is mediated by gap junctional communication in a JNK-dependent manner.

    PubMed

    Losa, Davide; Köhler, Thilo; Bellec, Jessica; Dudez, Tecla; Crespin, Sophie; Bacchetta, Marc; Boulanger, Pierre; Hong, Saw See; Morel, Sandrine; Nguyen, Tuan H; van Delden, Christian; Chanson, Marc

    2014-05-15

    Chronic infection and inflammation of the airways is a hallmark of cystic fibrosis (CF), a disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. The response of the CF airway epithelium to the opportunistic pathogen Pseudomonas aeruginosa is characterized by altered inflammation and apoptosis. In this study, we examined innate immune recognition and epithelial responses at the level of the gap junction protein connexin43 (Cx43) in polarized human airway epithelial cells upon infection by PAO1. We report that PAO1 activates cell surface receptors to elicit an intracellular signaling cascade leading to enhancement of gap junctional communication. Expression of Cx43 involved an opposite regulation exerted by JNK and p38 MAPKs. PAO1-induced apoptosis was increased in the presence of a JNK inhibitor, but latter effect was prevented by lentiviral expression of a Cx43-specific short hairpin RNA. Moreover, we found that JNK activity was upregulated by pharmacological inhibition of CFTR in Calu-3 cells, whereas correction of a CF airway cell line (CF15 cells) by adenoviral expression of CFTR reduced the activation of this MAPK. Interestingly, CFTR inhibition in Calu-3 cells was associated with decreased Cx43 expression and reduced apoptosis. These results indicate that Cx43 expression is a component of the response of airway epithelial cells to innate immune activation by regulating the survival/apoptosis balance. Defective CFTR could alter this equilibrium with deleterious consequences on the CF epithelial response to P. aeruginosa.

  2. Epithelial neoplasia in Drosophila entails switch to primitive cell states

    PubMed Central

    Khan, Sumbul J.; Bajpai, Anjali; Alam, Mohammad Atif; Gupta, Ram P.; Harsh, Sneh; Pandey, Ravi K.; Goel-Bhattacharya, Surbhi; Nigam, Aditi; Mishra, Arati; Sinha, Pradip

    2013-01-01

    Only select cell types in an organ display neoplasia when targeted oncogenically. How developmental lineage hierarchies of these cells prefigure their neoplastic propensities is not yet well-understood. Here we show that neoplastic Drosophila epithelial cells reverse their developmental commitments and switch to primitive cell states. In a context of alleviated tissue surveillance, for example, loss of Lethal giant larvae (Lgl) tumor suppressor in the wing primordium induced epithelial neoplasia in its Homothorax (Hth)-expressing proximal domain. Transcriptional profile of proximally transformed mosaic wing epithelium and functional tests revealed tumor cooperation by multiple signaling pathways. In contrast, lgl− clones in the Vestigial (Vg)-expressing distal wing epithelium were eliminated by cell death. Distal lgl− clones, however, could transform when both tissue surveillance and cell death were compromised genetically and, alternatively, when the transcription cofactor of Hippo signaling pathway, Yorkie (Yki), was activated, or when Ras/EGFR signaling was up-regulated. Furthermore, transforming distal lgl− clones displayed loss of Vg, suggesting reversal of their terminal cell fate commitment. In contrast, reinforcing a distal (wing) cell fate commitment in lgl− clones by gaining Vg arrested their neoplasia and induced cell death. We also show that neoplasia in both distal and proximal lgl− clones could progress in the absence of Hth, revealing Hth-independent wing epithelial neoplasia. Likewise, neoplasia in the eye primordium resulted in loss of Elav, a retinal cell marker; these, however, switched to an Hth-dependent primitive cell state. These results suggest a general characteristic of “cells-of-origin” in epithelial cancers, namely their propensity for switch to primitive cell states. PMID:23708122

  3. Epithelial neoplasia in Drosophila entails switch to primitive cell states.

    PubMed

    Khan, Sumbul J; Bajpai, Anjali; Alam, Mohammad Atif; Gupta, Ram P; Harsh, Sneh; Pandey, Ravi K; Goel-Bhattacharya, Surbhi; Nigam, Aditi; Mishra, Arati; Sinha, Pradip

    2013-06-11

    Only select cell types in an organ display neoplasia when targeted oncogenically. How developmental lineage hierarchies of these cells prefigure their neoplastic propensities is not yet well-understood. Here we show that neoplastic Drosophila epithelial cells reverse their developmental commitments and switch to primitive cell states. In a context of alleviated tissue surveillance, for example, loss of Lethal giant larvae (Lgl) tumor suppressor in the wing primordium induced epithelial neoplasia in its Homothorax (Hth)-expressing proximal domain. Transcriptional profile of proximally transformed mosaic wing epithelium and functional tests revealed tumor cooperation by multiple signaling pathways. In contrast, lgl(-) clones in the Vestigial (Vg)-expressing distal wing epithelium were eliminated by cell death. Distal lgl(-) clones, however, could transform when both tissue surveillance and cell death were compromised genetically and, alternatively, when the transcription cofactor of Hippo signaling pathway, Yorkie (Yki), was activated, or when Ras/EGFR signaling was up-regulated. Furthermore, transforming distal lgl(-) clones displayed loss of Vg, suggesting reversal of their terminal cell fate commitment. In contrast, reinforcing a distal (wing) cell fate commitment in lgl(-) clones by gaining Vg arrested their neoplasia and induced cell death. We also show that neoplasia in both distal and proximal lgl(-) clones could progress in the absence of Hth, revealing Hth-independent wing epithelial neoplasia. Likewise, neoplasia in the eye primordium resulted in loss of Elav, a retinal cell marker; these, however, switched to an Hth-dependent primitive cell state. These results suggest a general characteristic of "cells-of-origin" in epithelial cancers, namely their propensity for switch to primitive cell states.

  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. 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.

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

    PubMed Central

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

    2015-01-01

    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. PMID:26193301

  7. Hippo signaling promotes JNK-dependent cell migration

    PubMed Central

    Ma, Xianjue; Wang, Hongxiang; Ji, Jiansong; Xu, Wenyan; Sun, Yihao; Li, Wenzhe; Zhang, Xiaoping; Chen, Juxiang; Xue, Lei

    2017-01-01

    Overwhelming studies show that dysregulation of the Hippo pathway is positively correlated with cell proliferation, growth, and tumorigenesis. Paradoxically, the detailed molecular roles of the Hippo pathway in cell invasion remain debatable. Using a Drosophila invasion model in wing epithelium, we show herein that activated Hippo signaling promotes cell invasion and epithelial-mesenchymal transition through JNK, as inhibition of JNK signaling dramatically blocked Hippo pathway activation-induced matrix metalloproteinase 1 expression and cell invasion. Furthermore, we identify bantam-Rox8 modules as essential components downstream of Yorkie in mediating JNK-dependent cell invasion. Finally, we confirm that YAP (Yes-associated protein) expression negatively regulates TIA1 (Rox8 ortholog) expression and cell invasion in human cancer cells. Together, these findings provide molecular insights into Hippo pathway-mediated cell invasion and also raise a noteworthy concern in therapeutic interventions of Hippo-related cancers, as simply inhibiting Yorkie or YAP activity might paradoxically accelerate cell invasion and metastasis. PMID:28174264

  8. Neoplasia in vaginal cuff epithelial inclusion cysts after hysterectomy.

    PubMed

    Hoffman, M S; Roberts, W S; LaPolla, J P; Sterghos, S; Cavanagh, D

    1989-06-01

    Between Jan 1, 1985, and Dec 31, 1987, 26 women were treated for vaginal intraepithelial neoplasia (VAIN). Twenty-two of them had undergone hysterectomy, 15 for a cervical intraepithelial neoplasia or cancer. Five patients were identified whose management was complicated by the presence of the neoplastic process within vaginal cuff inclusion cysts (or sinuses). All five patients ultimately underwent upper vaginectomy as part of their treatment, and two of them were found to have an invasive squamous cell carcinoma of the vagina. Women who are found to have an abnormal Papanicolaou smear or VAIN in the upper vagina following hysterectomy should be examined carefully for vaginal cuff abnormalities. Those with nodularity or distortion of the cuff are best managed with surgical excision for both treatment of VAIN and discovery of an occult invasive cancer.

  9. Endoscopic diagnosis of early squamous neoplasia of the esophagus with iodine staining: high-grade intra-epithelial neoplasia turns pink within a few minutes.

    PubMed

    Shimizu, Yuichi; Omori, Tai; Yokoyama, Akira; Yoshida, Takeshi; Hirota, Jojo; Ono, Yuji; Yamamoto, Junji; Kato, Mototsugu; Asaka, Masahiro

    2008-04-01

    The ability to detect early squamous neoplasia of the esophagus can be enhanced considerably by iodine staining during endoscopic examination; however, there has been no study on distinguishing high-grade intra-epithelial squamous neoplasia from low-grade dysplasia by endoscopic examination. We assumed that high-grade intra-epithelial neoplasia could be identified as iodine-unstained areas more distinct and reddish than low-grade dysplasia after the brown color of iodine solution has faded, because there is almost no remaining glycogen-containing epithelium in high-grade intra-epithelial neoplasia. Seventy-nine patients who were found to have demarcated iodine-unstained areas (0.5 cm to 1.5 cm at widest part, 121 lesions in total) were studied. After a target lesion was found, the lesion was observed for about 3 min and its discoloration was evaluated. If a light-pink part appeared in the iodine-unstained area, the lesion was regarded as being positive for pink color. If no light-pink part was observed in the lesion within 3 min, the lesion was regarded as being negative for pink color. Thirty-four (87.2%) of the 39 lesions diagnosed as pink-color positive were histologically confirmed to be high-grade intra-epithelial squamous neoplasia or squamous cell carcinoma, whereas only three (3.7%) of the 82 lesions diagnosed as negative for pink color were histologically confirmed to be high-grade intra-epithelial squamous neoplasia (P < 0.0001). Using the pink-color sign as a diagnostic index for high-grade intra-epithelial squamous neoplasia and squamous cell carcinoma, sensitivity was 91.9% and specificity was 94.0%. By using the pink-color sign for endoscopic diagnosis, accurate diagnosis without endoscopic biopsy for iodine-unstained areas was possible.

  10. Antioxidant Prophylaxis in the Prevention of Prostatic Epithelial Neoplasia

    DTIC Science & Technology

    2009-02-01

    addition to increased variability in nuclear shape, chromasia, nucleolar spacing, cell crowding and cytoplasmic eosinophilia which sharply contrasted...contain protein with increased eosinophilia ; acinar walls are thickened with reactive hyperplastic epithelial cells. Low power magnification of prostate...cell infiltration into the stroma. The acini variably contain protein with increased eosinophilia ; acinar walls are thickened with reactive

  11. 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.

  12. p120 Catenin suppresses basal epithelial cell extrusion in invasive pancreatic neoplasia

    PubMed Central

    Hendley, Audrey M.; Wang, Yue J.; Polireddy, Kishore; Alsina, Janivette; Ahmed, Ishrat; Lafaro, Kelly J.; Zhang, Hao; Roy, Nilotpal; Savidge, Samuel G.; Cao, Yanna; Hebrok, Matthias; Maitra, Anirban; Reynolds, Albert B.; Goggins, Michael; Younes, Mamoun; Iacobuzio-Donahue, Christine A.; Leach, Steven D.; Bailey, Jennifer M.

    2016-01-01

    Aberrant regulation of cellular extrusion can promote invasion and metastasis. Here, we identify molecular requirements for early cellular invasion using a premalignant mouse model of pancreatic cancer with conditional knockout of p120 catenin (Ctnnd1). Mice with biallelic loss of p120 catenin progressively develop high grade PanIN lesions and neoplasia accompanied by prominent acute and chronic inflammatory processes, which is mediated in part through nuclear factor-kB (NF-kB) signaling. Loss of p120 catenin in the context of oncogenic Kras also promotes remarkable apical and basal epithelial cell extrusion. Abundant single epithelial cells exit PanIN epithelium basally, retain epithelial morphology, survive, and display features of malignancy. Similar extrusion defects are observed following p120 catenin knockdown in vitro, and these effects are completely abrogated by activation of S1P/S1pr2 signaling. In the context of oncogenic Kras, p120 catenin loss significantly reduces expression of genes mediating S1P/S1pr2 signaling in vivo and in vitro, and this effect is mediated at least in part through activation of NF-kB. These results provide insight into mechanisms controlling early events in the metastatic process and suggest that p120 catenin and S1P/S1pr2 signaling enhance cancer progression by regulating epithelial cell invasion. PMID:27032419

  13. Grasper type scissors for endoscopic submucosal dissection of gastric epithelial neoplasia

    PubMed Central

    Chung, Woo-Chul; Kim, Byung-Wook; Lim, Chul-Hyun; Kim, Tae-Ho; Park, Jae-Myung; Kim, Joon-Sung

    2013-01-01

    AIM: To evaluate the efficacy and safety of grasper type scissors (GTS) for endoscopic submucosal dissection (ESD) of gastric epithelial neoplasia. METHODS: The study was performed by 4 endoscopists in 4 institutions affiliated to The Catholic University of Korea. ESD was performed in 76 consecutive patients with gastric epithelial neoplasia by using the GTS (37 patients) or the hook knife plus coagrasper (HKC) (39 patients). The complete resection rate, complication rate, total time elapsed and elapsed time per square centimeter of the dissected specimen were analyzed between the GTS and HKC group. RESULTS: The mean age of the GTS group was 62.3 ± 11.4 years and mean age of the HKC group was 65.6 ± 10.1 years. Differentiated adenocarcinoma was found in 32.4% in the GTS group and 33.3% in the HKC group. The procedures were performed without interruption in every case in both groups. The en bloc resection rates of both groups were 100%. The total time elapsed during the procedure was 44.54 ± 21.72 min in the GTS group and 43.77 ± 21.84 min in the HKC group (P = 0.88) and the time elapsed per square centimeter of the resected lesion was 7.53 ± 6.35 min/cm2 in the GTS group and 6.92 ± 5.93 min/cm2 in the HKC group (P = 0.66). The overall complication rate was not significantly different between the two groups. CONCLUSION: GTS is a safe and effective device for ESD compared with HKC. ESD can be performed with GTS alone, which can reduce the costs for ESD. PMID:24115820

  14. [Endoscopic Submucosal dissection and mucosectomy for the treatment of the epithelial neoplasia and early gastric cancer].

    PubMed

    Barreda B, Fernando; Sanchez L, Juvenal

    2008-01-01

    In Japan, endoscopic mucosal resection and endoscopic submucosal dissection of early gastric cancer are accepted as a treatment options for cases of early gastric cancer where the probability of lymph node metastasis is nil or low. To establish the effectiveness of mucosectomy for the treatment of early gastric cancer and evaluate the extended indications for dysplasia lesions, also, we want to determine if the mucosectomy is relevant for lesions negative for neoplasia at the National Institute for Neoplastic Diseases (INEN), Lima, Peru. We call for estimating the utility and factibility of the endoscopic submucosa dissection with the needle knife. The study is an observational, prospective, analytical and cross longitudinal. The study was performed in 96 patients with Type 0 Neoplastic lesions at INEN from 1996 to 2008. The revised Vienna classification of gastrointestinal epithelial neoplasia was utilized. The indication for endoscopic mucosal resection as a radical treatment of early gastric cancer is according to the treatment guidelines for gastric cancer in Japan. The lesions were resected with a simple endoscopic snare, with the Olympus cap for some depressed lesions and the needle knife during the submucosal dissection. Lifting of the lesion with submucosal injection was done with saline solution with epinephrine or saline with distillate water. The statistical analysis included the SPPS-12 programme. 96 patients were treated by mucosectomy and endoscopic submucosal dissection from 1996 to 2008. The sample represents patients with a mean age over 50 years old and predominance of female. 55 patients belongs to category 1 of revised Vienna Classification, 9 patients are in the category 3, 31 patients are suitable in category 4 (20 with high grade adenoma/dysplasia and 11 with intramucosal carcinoma) and just 1 patient for the category 5. We resected 305 Type 0 lesions, 85 mucosal neoplasia, low grade (43) and high grade (31 adenoma/dysplasia in 20 patients

  15. Prevalence and incidence of cervical intra-epithelial neoplasia among female sex workers in Korogocho, Kenya.

    PubMed

    Njagi, S K; Mugo, N R; Reid, A J; Satyanarayana, S; Tayler-Smith, K; Kizito, W; Kwatampora, J; Waweru, W; Kimani, J; Smith, J S

    2013-12-21

    Sex Workers Outreach Programme Clinic, Korogocho, Nairobi, Kenya. In a cohort of sex workers, to determine 1) the prevalence of cervical intra-epithelial neoplasia (CIN) and its association with human immunodeficiency virus-1 (HIV-1) infection, and 2) the incidence rate of CIN during the 3-year follow-up from December 2009 to December 2012. Prospective nested cohort study. Of the 350 women enrolled, the median age was 29 years (range 18-49); 84 (24%) were HIV-1-infected. At enrollment, 54 (15%) had an abnormal cytology, 39 (11%) had low-grade intra-epithelial lesions (LSIL) and 15 (4%) high-grade intraepithelial lesions (HSIL). HIV-1-infected women were 2.7 times (95%CI 1.7-4.4) more likely to have CIN than non-HIV-1-infected women. Among HIV-1-infected women, the prevalence of LSIL and HSIL was 2.5 times (95%CI 1.2-5.1) and seven times (95%CI 2.3-23.3) greater than among non-HIV-infected women. During the follow-up period, 39 (11%) women had incident CIN (6.6/100 person years [py]), with no difference by HIV status, i.e., respectively 7.9/100 py and 6.3/100 py in HIV-1-infected and non-HIV-1-infected women. The prevalence and incidence of CIN among HIV-1-infected sex workers was high; early, regular screening and follow-up of this life-threatening condition is therefore recommended.

  16. 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

  17. Expression of p53 predicts risk of prevalent and incident advanced neoplasia in patients with Barrett's esophagus and epithelial changes indefinite for dysplasia.

    PubMed

    Horvath, Bela; Singh, Prabhdeep; Xie, Hao; Thota, Prashanthi N; Sun, Xingwen; Liu, Xiuli

    2016-11-01

    Patients with Barrett's esophagus (BE) are at an increased risk for developing esophageal adenocarcinoma (EAC); thus they may undergo regular endoscopic surveillance. If epithelial changes cannot be unequivocally classified as negative or positive for dysplasia, a diagnosis of indefinite for dysplasia (IND) is recommended. Several biomarkers have been proposed as markers or predictors of neoplasia in the general BE population; however, their significance is not clear in patients with BE-IND. We therefore performed a retrospective study to determine whether expression of these biomarkers was associated with the development of neoplasia in BE-IND patients. We searched our archives to identify all cases of BE-IND diagnosed between January 1992 and December 2007. Immunohistochemical analyses were used to semi-quantify the expression of p53, α-methylacyl-CoA racemase (AMACR), and cyclin D1. A univariate analysis was used to identify predictors for prevalent and incident neoplasia and advanced neoplasia. Among the 103 patients with an index diagnosis of BE-IND who were included in this study, 81 (78.6%) underwent a follow-up biopsy within 12 months of diagnosis; 10 (12.3%) had neoplasia, including four (4.9%) with advanced neoplasia. Among 79 patients without prevalent neoplasia who underwent more than 1 year of follow-up, 18 (22.8%) had developed neoplasia, including four (5.1%) with advanced neoplasia. AMACR and cyclin D1 expression levels were not correlated with prevalent or incident neoplasia; however, high p53 expression (>5%) was associated with prevalent advanced neoplasia on surveillance biopsy (P = 0.04) and with an increased risk of progression to advanced neoplasia (HR = 12; P = 0.03). In this study, p53 expression was found to be predictive of prevalent advanced neoplasia and progression to advanced neoplasia in patients with BE-IND. © The Author(s) 2015. Published by Oxford University Press and the Digestive Science Publishing Co. Limited.

  18. 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

  19. JNK-dependent gene regulatory circuitry governs mesenchymal fate

    PubMed Central

    Sahu, Sanjeeb Kumar; Garding, Angela; Tiwari, Neha; Thakurela, Sudhir; Toedling, Joern; Gebhard, Susanne; Ortega, Felipe; Schmarowski, Nikolai; Berninger, Benedikt; Nitsch, Robert; Schmidt, Marcus; Tiwari, Vijay K

    2015-01-01

    The epithelial to mesenchymal transition (EMT) is a biological process in which cells lose cell–cell contacts and become motile. EMT is used during development, for example, in triggering neural crest migration, and in cancer metastasis. Despite progress, the dynamics of JNK signaling, its role in genomewide transcriptional reprogramming, and involved downstream effectors during EMT remain largely unknown. Here, we show that JNK is not required for initiation, but progression of phenotypic changes associated with EMT. Such dependency resulted from JNK-driven transcriptional reprogramming of critical EMT genes and involved changes in their chromatin state. Furthermore, we identified eight novel JNK-induced transcription factors that were required for proper EMT. Three of these factors were also highly expressed in invasive cancer cells where they function in gene regulation to maintain mesenchymal identity. These factors were also induced during neuronal development and function in neuronal migration in vivo. These comprehensive findings uncovered a kinetically distinct role for the JNK pathway in defining the transcriptome that underlies mesenchymal identity and revealed novel transcription factors that mediate these responses during development and disease. PMID:26157010

  20. Endoscopic submucosal dissection using a thulium laser: preliminary results of a new method for treatment of gastric epithelial neoplasia.

    PubMed

    Cho, Jun-Hyung; Cho, Joo Young; Kim, Mi-Young; Jeon, Seong Ran; Lee, Tae Hee; Kim, Hyun Gun; Jin, So Young; Hong, Su Jin

    2013-09-01

    This study aimed to evaluate the feasibility of a novel laser system for endoscopic submucosal dissection (ESD) of gastric epithelial neoplasia. A total of 10 patients underwent ESD by a single expert endoscopist. A thulium 2-μm wavelength laser system was used for ESD procedures. Instead of using endoscopy knives, a 550-μm flexible silica fiber was inserted through the working channel of the endoscope. In all patients, ESD was completed using only the thulium laser, without the need for endoscopy knives. The median total procedure time was 49 minutes (range 35 - 203). In 8 /10 patients (80 %), no active bleeding was observed during ESD. The final pathologic mapping revealed low-grade dysplasia (n = 4), differentiated adenocarcinoma (n = 5), and signet ring cell carcinoma (n = 1). Curative resection was achieved in 9 /10 patients (90 %). There were no significant complications, such as delayed bleeding or perforation. The thulium laser system was feasible in ESD of gastric epithelial neoplasia. © Georg Thieme Verlag KG Stuttgart · New York.

  1. 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.

  2. Hexose uptake in 7,12-dimethylbenz(a)anthracene-preexposed rat tracheal epithelial cells during the progression of neoplasia

    SciTech Connect

    Wasilenko, W.J.; Marchok, A.C.

    1984-07-01

    Hexose uptake during the progression of neoplasia in rat tracheal epithelial cells was studied by measuring the uptake of 2-deoxy(/sup 3/H)glucose (2-dGlc) in nontumorigenic (C-18) and tumorigenic (T-8, 1000-WT) rat tracheal epithelial cell lines with varying degrees of cell association as well as in: (a) normal primary cell cultures (NPC) derived from explants of nonexposed tracheas; (b) selected primary cell cultures (SPC) generated from explants of 7,12-dimethylbenz(a)anthracene-treated tracheal implants; and (c) primary tumor cell cultures (TPC) derived from explants of 7,12-dimethylbenz(a)anthracene-induced tracheal carcinomas. The latter two groups represented cells from earlier and late states in the progression of neoplasia, respectively, and each displayed an in vitro growth advantage that allowed for their survival and growth in medium devoid of supplements of pyruvate and insulin. This property was used in this study to select the carcinogen-altered cells from neighboring normal cells. Uptake of 2-dGlc per ..mu..g of DNA was similar in subconfluent cultures of all cell lines. At confluency, uptake per ..mu..g of DNA was reduced markedly (>3-fold) in C-18 cells but it was reduced only 1.3-fold in T-8 cells and 1.6-fold in 1000-WT cells. Hexose uptake was further reduced in T-8 and 1000-WT cell cultures generated as outgrowths from explants of denuded tracheas bearing a reestablished epithelium from each cell line. Under these conditions, T-8 cells retained higher 2-dGlc uptake than did C-18, but uptake by 1000-WT was lower, indicating that tissue-like cell associations have a profound effect on hexose uptake in these epithelial cells. Results were generally similar when uptake was expressed per mg of protein although, in several instances, the interpretation of uptake data was affected by differences in the protein content between cultures. 46 references, 1 figure, 7 tables.

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

    SciTech Connect

    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.

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

    PubMed Central

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

    2015-01-01

    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. PMID:26202785

  5. 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.

  6. Virological and cytological clearance in laser vaporization and conization for cervical intra-epithelial neoplasia grade 3.

    PubMed

    Mariya, Tasuku; Nishikawa, Akira; Sogawa, Kanae; Suzuki, Riri; Saito, Masae; Kawamata, Akari; Shimizu, Ayumi; Nihei, Takehito; Sonoda, Tomoko; Saito, Tsuyoshi

    2016-12-01

    Cervical intra-epithelial neoplasia (CIN) is the precancerous stage of cervical cancer. Standard treatment for high-grade CIN is conization of the cervix. The risk of preterm birth following conization has been discussed recently. In contrast, laser vaporization is believed not to affect perinatal outcome, but the long-term effectiveness of each surgical procedure is still unclear. The aim of this prospective unmatched-cohort study was therefore to compare virological and cytological clearance and recurrence risk between conization and vaporization for CIN3. Subject consisted of CIN3 patients treated at the present hospital between 2007 to 2011 and followed up until December 2014. One hundred and one patients were treated with laser conization, and 137 with vaporization. The surgical procedure was selected on the basis of colposcopy, pathological grade and patient's hope for pregnancy. There were no significant differences in cure rate, human papilloma virus (HPV) clearance rate or recurrence rates between the conization and vaporization groups. Risk ratio of recurrence for each surgical procedure adjusted for age and HPV persistence status were analyzed on Cox proportional hazards modeling. Recurrence risk ratio for patients treated by vaporization was 6.21 (95%CI: 0.65-59.19; P = 0.111) compared with conization and there were no significant differences. No adverse pregnancy outcome was observed in the vaporization group compared with conization. Laser vaporization is useful for young patients with CIN3 who hope for pregnancy in the future. © 2016 Japan Society of Obstetrics and Gynecology.

  7. A central role for vesicle trafficking in epithelial neoplasia: Intracellular highways to carcinogenesis

    PubMed Central

    Goldenring, James R.

    2014-01-01

    Epithelial cell carcinogenesis involves the loss of polarity, alteration of polarized protein presentation, dynamic cell morphology changes, increased proliferation and increased cell motility and invasion. Elements of membrane vesicle trafficking underlie all of these processes. Specific membrane trafficking regulators, including Rab small GTPases, through the coordinated dynamics of intracellular trafficking along cytoskeletal pathways, determine cell surface presentation of proteins and overall function of both differentiated and neoplastic cells. While mutations in vesicle trafficking proteins may not be direct drivers of transformation, elements of the machinery of vesicle movement play critical roles in the phenotypes of neoplastic cells. Therefore, the regulators of membrane vesicle trafficking decisions are critical mediators of the full spectrum of cell physiologies driving cancer cell biology, including initial loss of polarity, invasion and metastasis. Targeting of these fundamental intracellular processes may provide important points for manipulation of cancer cell behaviour. PMID:24108097

  8. A central role for vesicle trafficking in epithelial neoplasia: intracellular highways to carcinogenesis.

    PubMed

    Goldenring, James R

    2013-11-01

    Epithelial cell carcinogenesis involves the loss of cell polarity, alteration of polarized protein presentation, dynamic cell morphology changes, increased proliferation, and increased cell motility and invasion. Membrane vesicle trafficking underlies all of these processes. Specific membrane trafficking regulators, including RAB small GTPases, through the coordinated dynamics of intracellular trafficking along cytoskeletal pathways, determine the cell surface presentation of proteins and the overall function of both differentiated and neoplastic cells. Although mutations in vesicle trafficking proteins may not be direct drivers of transformation, components of the machinery of vesicle movement have crucial roles in the phenotypes of neoplastic cells. Therefore, the regulators of membrane vesicle trafficking decisions are essential mediators of the full range of cell physiologies that drive cancer cell biology, including initial loss of cell polarity, invasion and metastasis. Targeting of these fundamental intracellular processes may permit the manipulation of cancer cell behaviour.

  9. Integrated approach to prediction of cervical intra-epithelial neoplasia status through a case-control study.

    PubMed

    Sengupta, S; Chaudhuri, S K; Das, P; Raichaudhuri, B; Pramanik, R

    1999-02-19

    A case-control study on cervical intra-epithelial neoplasia (CIN) was carried out on 398 subjects in the state of West Bengal, India. These samples were taken from mass screening programs organized by the authors, maintaining the uniformity of sampling to the extent possible. The cervical smears were tested by the Papanicolaou (PAP) method, following the Bethesda system for reporting of CIN status. Odds ratios and correlation coefficients among different variables, assumed to produce carcinoma of the cervix, show that 6 out of 11 variables, i.e., age, education, socio-economic status, duration of marriage, age at marriage and body surface, are associated with CIN. Multivariate analysis of logistic regression was carried out using BMDP-LR with dichotomized response variables considering CIN (0 and 1) in one group and CIN (2 and 3) in the other group. The outcome of the analysis indicated that age and educational level are 2 contributing factors for CIN. The percentage of correct classification in this analysis has improved to 74.5%, with a probability of 0.90. Polychotomous regression analysis was carried out using BMDP-PR in the next step. This analysis showed that parity was a contributing factor, in addition to age and educational level. These 3 factors provide a predictive model for identifying the high-risk group in a rational way. This approach would restrict screening to approximately 10% of the population. Subsequently, the model has been validated in a confirmatory trial among 85 new cases and was found to work satisfactorily.

  10. 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.

  11. Neutralising antibody against type 1 and type 2 herpes simplex virus in cervical mucus of women with cervical intra-epithelial neoplasia.

    PubMed

    Murphy, J F; Murphy, D F; Barker, S; Mylotte, M L; Coughlan, B M; Skinner, G R

    1985-01-01

    Patients with cervical intra-epithelial neoplasia had significantly increased neutralising antibody activity to type 2 herpes simplex virus in the cervical mucus. While patients differed from control subjects with respect to their number of sexual partners and socio-economic class, there were significant differences in neutralising antibody activity for case control comparisons within the same number of sexual partners or socio-economic groupings. The results lend support to the putative association between type 2 herpes simplex virus infection and pre-invasive and invasive carcinoma of the uterine cervix.

  12. Icaritin activates JNK-dependent mPTP necrosis pathway in colorectal cancer cells.

    PubMed

    Zhou, Chunxian; Chen, Zhengrong; Lu, Xingsheng; Wu, Hao; Yang, Qunying; Xu, Dongfeng

    2016-03-01

    The colorectal cancer (CRC) is one leading contributor of cancer-related mortality worldwide. The search for effective anti-CRC agents is valuable. In the current study, we showed that icaritin (ICT), an active natural ingredient from the Chinese plant Epimedium, potently inhibited proliferation and survival of established (HT-29, HCT-116, DLD-1, and SW-620) and primary (patient-derived) CRC cells. Significantly, ICT mainly induced necrosis, but not apoptosis, in CRC cells. The necrosis inhibitor necrostatin-1 attenuated ICT-mediated cytotoxicity in CRC cells. We showed that ICT treatment in CRC cells induced mitochondrial permeability transition pore (mPTP) opening, which was evidenced by mitochondrial membrane potential (MMP) decrease and mitochondrial adenine nucleotide translocator-1 (ANT-1)-cyclophilin-D (CyPD) association. On the other hand, mPTP blockers, including sanglifehrin A, cyclosporin A, and bongkrekic acid, as well as siRNA-mediated knockdown of mPTP component (CyPD or ANT-1), significantly alleviated ICT-mediated cytotoxicity against CRC cells. We suggested that Jun-N-terminal kinase (JNK) activation by ICT mediated mPTP opening and subsequent CRC cell necrosis. JNK pharmacological inhibition, dominant negative mutation, or shRNA downregulation suppressed ICT-induced MMP reduction and subsequent HT-29 cell necrosis. In vivo, oral gavage of ICT dramatically inhibited HT-29 xenograft growth in nude mice. The in vivo activity by ICT was largely attenuated by co-administration with the mPTP blocker CsA. Collectively, our results showed that ICT exerts potent inhibitory effect against CRC cells in vitro and in vivo. JNK-dependent mPTP necrosis pathway could be key mechanism responsible for ICT's actions.

  13. COX-2 (PTGS2) gene methylation in epithelial, subepithelial lymphocyte and stromal tissue compartments in a spectrum of esophageal squamous neoplasia.

    PubMed

    Dawsey, Sonja P; Roth, Mark J; Adams, Lisa; Hu, Nan; Wang, Quan-Hong; Taylor, Philip R; Woodson, Karen

    2008-01-01

    Previous studies have shown important effects of stromal elements in carcinogenesis. To explore the tumor-stromal relationship in esophageal neoplasia, we examined methylation of COX-2 (PTGS2), a gene etiologically associated with the development of gastrointestinal cancers, in adjacent foci of epithelium, subepithelial lymphocytes and non-lymphocytic stromal cells found in sections of normal squamous epithelium, squamous dysplasia and invasive esophageal squamous cell carcinoma. Adjacent foci of epithelium, subepithelial lymphocytic aggregates and non-lymphocytic stromal tissues were laser microdissected from six fully embedded, ethanol fixed, esophagectomy samples from Shanxi, China, a high-risk region for esophageal cancer. Promoter CpG site-specific hypermethylation status of COX-2 was determined using real-time methylation-specific PCR (qMS-PCR) based on Taqman Chemistry. The methylation status of a subset of samples was confirmed by pyrosequencing. Forty-nine microdissected foci were analyzed. COX-2 gene methylation was significantly more common in subepithelial lymphocytes (12/16 (75% of all foci)) than in epithelial foci (3/16 (19%)) or foci of non-lymphocytic stromal tissues (3/17 (18%)) (Fisher's exact p=0.05). Two of three epithelial samples and all three stromal samples that showed COX-2 methylation were adjacent to foci of methylated subepithelial lymphocytes. Pyrosequencing confirmed the methylation status in a subset of samples. In these esophageal cancer patients, COX-2 gene methylation was more common in subepithelial lymphocytes than in adjacent epithelial or stromal cells in both grades of dysplasia and in foci of invasive cancer. These findings raise the possibility that methylation of subepithelial lymphocytes may be important for tumorigenesis. Future studies of gene methylation should consider separate evaluation of epithelial and non-epithelial cell populations.

  14. From Normalcy to Neoplasia. The Role of Epithelial-Stromal Interactions in Regulating Mammary Growth and Differentiation

    DTIC Science & Technology

    2000-08-01

    the gland invades the fat pad and forms a small bud of epithelial cells. This epithelial cell bud will grow into a tree-like structure after puberty ...al., 1988). Ligands of the epidermal growth hormonally regulated ductal development during puberty and factor receptor (EGFR) are believed to be...A few exceptional Image programn (developed at the US National Institutes of Health and Eg/-Ir- mice survived until the age of puberty , when

  15. COX2 (PTGS2) gene methylation in epithelial, subepithelial lymphocyte and stromal tissue compartments in a spectrum of esophageal squamous neoplasia

    PubMed Central

    Dawsey, Sonja P.; Roth, Mark J.; Adams, Lisa; Hu, Nan; Wang, Quan-Hong; Taylor, Philip R.; Woodson, Karen

    2008-01-01

    Background Previous studies have shown important effects of stromal elements in carcinogenesis. To explore the tumor-stromal relationship in esophageal neoplasia, we examined methylation of COX-2 (PTGS2), a gene etiologically associated with the development of gastrointestinal cancers, in adjacent foci of epithelium, subepithelial lymphocytes and non-lymphocytic stromal cells found in sections of normal squamous epithelium, squamous dysplasia and invasive esophageal squamous cell carcinoma. Methods Adjacent foci of epithelium, subepithelial lymphocytic aggregates and non-lymphocytic stromal tissues were laser microdissected from six fully embedded, ethanol fixed, esophagectomy samples from Shanxi, China, a high-risk region for esophageal cancer. Promoter CpG site-specific hypermethylation status of COX-2 was determined using real-time methylation specific PCR (qMS-PCR) based on Taqman Chemistry. The methylation status of a subset of samples was confirmed by pyrosequencing. Results Forty-nine microdissected foci were analyzed. COX-2 gene methylation was significantly more common in subepithelial lymphocytes (12/16 (75% of all foci)) than in epithelial foci (3/16 (19%)) or foci of non-lymphocytic stromal tissues (3/17 (18%)) (Fisher’s Exact p=0.05). Two of three epithelial samples and all three stromal samples that showed COX-2 methylation were adjacent to foci of methylated subepithelial lymphocytes. Pyrosequencing confirmed the methylation status in a subset of samples. Conclusions In these esopohageal cancer patients, COX-2 gene methylation was more common in subepithelial lymphocytes than in adjacent epithelial or stromal cells in both grades of dysplasia and in foci of invasive cancer. These findings raise the possibility that methylation of subepithelial lymphocytes may be important for tumorigenesis. Future studies of gene methylation should consider separate evaluation of epithelial and non-epithelial cell populations. Condensed abstract COX2 (PTGS2) gene

  16. In-vivo nonlinear optical microscopy (NLOM) of epithelial-connective tissue interface (ECTI) reveals quantitative measures of neoplasia in hamster oral mucosa.

    PubMed

    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. 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

  18. Ovarian epithelial neoplasia after hormonal infertility treatment: long-term follow-up of a historical cohort in Sweden.

    PubMed

    Sanner, Karin; Conner, Peter; Bergfeldt, Kjell; Dickman, Paul; Sundfeldt, Karin; Bergh, Torbjörn; Hagenfeldt, Kerstin; Janson, Per Olof; Nilsson, Staffan; Persson, Ingemar

    2009-04-01

    To study the association between hormonal infertility treatment and ovarian neoplasia. Historical cohort study. Three university hospitals in Sweden. A total of 2,768 women assessed and treated for infertility and infertility-associated disorders between 1961 and 1975. Exposed women received clomiphene citrate and/or gonadotropins. Incidence of ovarian neoplasia. No overall excess risk of invasive ovarian cancer emerged compared with the general population. In women with gonadotropin treatment for non-ovulatory disorders, the risk was elevated (standardized incidence ratio [SIR] = 5.89; 95% confidence interval [CI] 1.91-13.75); four of the five cases reported hCG treatment only, rendering the biological plausibility uncertain. Multivariate analysis within the cohort indicated that treatment with gonadotropins only was associated with an increased risk of invasive cancer (relative risk = 5.28; 95% CI 1.70-16.47). For borderline tumors, a more than threefold overall increase of tumors (SIR = 3.61; 95% CI 1.45-7.44) was noted; women exposed to clomiphene because of ovulatory disorders showed the highest risk (SIR = 7.47; 95% CI 1.54-21.83). Our findings of increased risk of ovarian cancer after gonadotropins and of borderline tumors after clomiphene treatment need to be interpreted with caution. However, concern is raised, and further research on the long-term safety particularly of modern hormonal infertility treatment in IVF programs is warranted.

  19. Apical deficiency triggers JNK-dependent apoptosis in the embryonic epidermis of Drosophila

    PubMed Central

    Kolahgar, Golnar; Bardet, Pierre-Luc; Langton, Paul F.; Alexandre, Cyrille; Vincent, Jean-Paul

    2011-01-01

    Epithelial homeostasis and the avoidance of diseases such as cancer require the elimination of defective cells by apoptosis. Here, we investigate how loss of apical determinants triggers apoptosis in the embryonic epidermis of Drosophila. Transcriptional profiling and in situ hybridisation show that JNK signalling is upregulated in mutants lacking Crumbs or other apical determinants. This leads to transcriptional activation of the pro-apoptotic gene reaper and to apoptosis. Suppression of JNK signalling by overexpression of Puckered, a feedback inhibitor of the pathway, prevents reaper upregulation and apoptosis. Moreover, removal of endogenous Puckered leads to ectopic reaper expression. Importantly, disruption of the basolateral domain in the embryonic epidermis does not trigger JNK signalling or apoptosis. We suggest that apical, not basolateral, integrity could be intrinsically required for the survival of epithelial cells. In apically deficient embryos, JNK signalling is activated throughout the epidermis. Yet, in the dorsal region, reaper expression is not activated and cells survive. One characteristic of these surviving cells is that they retain discernible adherens junctions despite the apical deficit. We suggest that junctional integrity could restrain the pro-apoptotic influence of JNK signalling. PMID:21693518

  20. 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.

  1. Low Discrepancy Between Tissue Biopsy Plus Magnifying Endoscopy With Narrow-Band Imaging and Endoscopic Resection in the Diagnosis of Gastric Epithelial Neoplasia (STROBE)

    PubMed Central

    Zhang, Qiang; Lian, Zhou Yang; Chen, Zhen Yu; Wang, Zhen; di Chen, Chu; An, Sheng li; Gong, Wei; Zhi, Fa chao; de Liu, Si

    2015-01-01

    Abstract Tissue biopsy is often not very accurate for the diagnosis of gastric epithelial neoplasia (GEN), and the results differ notably from endoscopic resection (ER) in terms of the pathological diagnosis. The aims of this study were to evaluate the diagnostic performances of biopsy, magnifying endoscopy with narrow-band imaging (ME-NBI), and biopsy plus ME-NBI for GEN. This study retrospectively analyzed 101 cases diagnosed as GEN using ER samples. The discrepancies between biopsy and ER, as well as between biopsy plus ME-NBI and ER in the diagnosis of GEN were evaluated. Factors that contributed to such discrepancies were analyzed. The sensitivity and specificity of biopsy and ME-NBI for the diagnosis of high-grade neoplasia (HGN) were determined. The discrepancy in the pathological diagnosis between biopsy and ER was 39.6% for GEN and 54.2% for HGN. The discrepancy between biopsy combined with ME-NBI and ER was 15.9% for GEN and 10.2% for HGN. Factors that undermined the diagnostic accuracy of biopsy included the lesion size (≤10 mm, odds ratio [OR] 1; 10–20 mm, OR 0.2, 95% confidence interval [CI] 0.1–0.7; >20 mm, OR 0.5, 95% CI 0.1–2.1, P = 0.03) and the number of biopsy fragments (OR 0.6, 95% CI 0.5–0.8, P = 0.001). The sensitivity and specificity for HGN were 45.8% (33.7%–58.3%) and 100% (87.5%–100%) for biopsy, and 88.1% (77.5%–94.1%) and 92.9% (81.0%–97.5%) for ME-NBI, respectively. In conclusion, biopsy-based diagnoses for GEN should be interpreted with caution. Biopsy combined with ME-NBI can contribute to the diagnosis of GEN, which improves diagnostic consistency with pathological result of ER specimens. PMID:26166094

  2. Factors associated with HPV persistence after treatment for high-grade cervical intra-epithelial neoplasia with large loop excision of the transformation zone (LLETZ).

    PubMed

    Sarian, Luís Otávio Zanatta; Derchain, Sophie Françoise Mauricette; Pitta, Denise da Rocha; Morais, Sirlei Siani; Rabelo-Santos, Silvia Helena

    2004-12-01

    Human Papillomavirus (HPV) persistence after high-grade cervical intra-epithelial neoplasia (CIN) removal may be associated with residual lesions or risk of disease recurrence. Knowledge regarding the factors associated with HPV persistence following CIN treatment is still limited. The main purpose of this longitudinal study was to assess the association between characteristics of the patients and their cervical lesions with high-risk HPV-type persistence, detected by commercially available Hybrid Capture II (HC II), after CIN 2 and 3 treatment with large loop excision of the transformation zone (LLETZ). For this cohort study, a total of 94 women submitted to LLETZ between March 2001 and September 2002 were included. Only women with at least one follow-up visit at 6 or 12 months and confirmed CIN 2 or 3 in the cone specimen were considered. In each visit women answered to a questionnaire and undertook Pap smear and HC II specimens collection. McNemar's, chi-square and Fisher tests were used for univariate analysis. Generalized Estimating Equations (GEE) were used for multivariate analysis. All calculations were performed within 95% confidence intervals (95% CI). Histological evaluation showed 12 (13%) women with CIN, 2 and 82 (87%) with CIN 3 and conization margins were compromised in 27 (29%) cases. Eighty-seven (92%) women showed positive HC II tests prior to LLETZ. Of women initially HPV negative, none had a positive HC II during follow-up. The proportion of positive HPV tests was reduced from 92% to 20%(P < 0.01) at the first visit and to 22% (P < 0.01) at the second visit after LLETZ. Multivariate analysis showed that smoking and age above 35 years (irrespective of margin status) were strongly associated with positive HPV during follow-up. HPV persistence following LLETZ was associated with smoking and with the interaction between age and conization margins.

  3. KLF4 and PCNA identify stages of tumor initiation in a conditional model of cutaneous squamous epithelial neoplasia

    PubMed Central

    Huang MD, Conway C.; Liu, Zhaoli; Li, Xingnan; Bailey, Sarah K.; Nail, Clinton D.; Foster, K. Wade; Frost, Andra R.; Ruppert, J. Michael; Lobo-Ruppert, Susan M.

    2006-01-01

    KLF4 is induced upon growth-arrest in vitro and during epithelial maturation in vivo, and is essential for proper cell fate specification of post-mitotic cells. In spite of a normal role in post-mitotic cells, expression is upregulated and constitutive in certain tumor types. KLF4 functions as an oncogene in vitro, and enforced expression in basal cells of mouse skin rapidly induces lesions similar to hyperplasia, dysplasia and squamous cell carcinoma (SCC). Here we used conditional expression to characterize early steps in KLF4-mediated tumor initiation. In contrast to SCC-like lesions that result when using a conditional, keratin 14 promoter-dependent strategy, lower conditional expression achieved using a MMTV promoter induced only epidermal cycling within morphologically normal skin, a process we termed occult cell turnover. Surprisingly, KLF4-induced hyperplastic lesions showed increased transgene-derived mRNA and protein in maturing, PCNA-negative cells, a property of endogenous KLF4. In contrast, hyperplastic lesions induced by GLI1, a control, showed uniform transgene expression. In KLF4-induced dysplasia and SCC the complementarity of KLF4 and PCNA was replaced by concordance of the two proteins. These studies show that KLF4 transcripts are normally suppressed in cycling cells in a promoter-independent fashion, consistent with a post-transcriptional control, and reveal loss of this control in the transition from hyperplasia to dysplasia. Like the mouse tumors, human cutaneous SCCs and adjacent dysplasias frequently showed maturation-independence of KLF4, with co-expression of KLF4 and PCNA. A smaller subset of human SCCs showed complementarity of KLF4 and PCNA, similar to hyperplastic mouse skin. The results identify parallels between a mouse model and human primary tumors, and show that successive increases of KLF4 in the nuclei of basal keratinocytes leads to occult cell turnover followed by hyperplasia, dysplasia, and invasive SCC. PMID:16357510

  4. Efficacy of endoscopic submucosal dissection with dental floss clip traction for gastric epithelial neoplasia: a pilot study (with video).

    PubMed

    Yoshida, Masao; Takizawa, Kohei; Ono, Hiroyuki; Igarashi, Kimihiro; Sugimoto, Shinya; Kawata, Noboru; Tanaka, Masaki; Kakushima, Naomi; Ito, Sayo; Imai, Kenichiro; Hotta, Kinichi; Matsubayashi, Hiroyuki

    2016-07-01

    Providing appropriate tension to the lesion and securing a stable view of the submucosal layer is important for accomplishing successful endoscopic submucosal dissection (ESD) in gastric cancer. Dental floss clip traction (DFC), a new traction method, is proposed to reduce the difficulty of ESD. The objective of this pilot study was to investigate the efficacy of DFC for gastric ESD. From August to November 2014, a total of 95 patients with 104 gastric epithelial neoplasms underwent DFC-ESD (DFC group). Historical controls treated by conventional ESD (control group) were individually matched to cases at a 1:1 ratio by lesion location, ulcer findings, resected specimen size, and the proficiency of the operator (trainee/expert). The outcomes of the procedure in the two groups were then compared. The mean ± SD procedure time was 43 ± 24 min in the DFC group and 52 ± 30 min in the control group (P < 0.01). Fewer lesions in the DFC group needed >80 min compared with the control group (3-vs-16 cases, P = 0.01). There were no significant differences in adverse events between the groups. Perforation and delayed bleeding occurred in one and four lesions, respectively, in the DFC group, and three and nine in the control group. En bloc resection was achieved in all cases. No significant differences were found regarding curability of ESD between the groups. DFC effectively reduced ESD procedure time without increasing adverse events. DFC is helpful for rapid, safe ESD.

  5. KLF4 and PCNA identify stages of tumor initiation in a conditional model of cutaneous squamous epithelial neoplasia.

    PubMed

    Huang, Conway C; Liu, Zhaoli; Li, Xingnan; Bailey, Sarah K; Nail, Clinton D; Foster, K Wade; Frost, Andra R; Ruppert, J Michael; Lobo-Ruppert, Susan M

    2005-12-01

    KLF4 is induced upon growth-arrest in vitro and during epithelial maturation in vivo, and is essential for proper cell fate specification of post-mitotic cells. In spite of a normal role in post-mitotic cells, expression is upregulated and constitutive in certain tumor types. KLF4 functions as an oncogene in vitro, and enforced expression in basal cells of mouse skin rapidly induces lesions similar to hyperplasia, dysplasia and squamous cell carcinoma (SCC). Here we used conditional expression to characterize early steps in KLF4-mediated tumor initiation. In contrast to SCC-like lesions that result when using a conditional, keratin 14 promoter-dependent strategy, lower conditional expression achieved using a MMTV promoter induced only epidermal cycling within morphologically normal skin, a process we termed occult cell turnover. Surprisingly, KLF4-induced hyperplastic lesions showed increased transgene-derived mRNA and protein in maturing, PCNA-negative cells, a property of endogenous KLF4. In contrast, hyperplastic lesions induced by GLI1, a control, showed uniform transgene expression. In KLF4-induced dysplasia and SCC the complementarity of KLF4 and PCNA was replaced by concordance of the two proteins. These studies show that KLF4 transcripts are normally suppressed in cycling cells in a promoter-independent fashion, consistent with a post-transcriptional control, and reveal loss of this control in the transition from hyperplasia to dysplasia. Like the mouse tumors, human cutaneous SCCs and adjacent dysplasias frequently showed maturation-independence of KLF4, with co-expression of KLF4 and PCNA. A smaller subset of human SCCs showed complementarity of KLF4 and PCNA, similar to hyperplastic mouse skin. The results identify parallels between a mouse model and human primary tumors, and show that successive increases of KLF4 in the nuclei of basal keratinocytes leads to occult cell turnover followed by hyperplasia, dysplasia, and invasive SCC.

  6. 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.

  7. The preventive effects of taurine on neural tube defects through the Wnt/PCP-Jnk-dependent pathway.

    PubMed

    Zhang, Qinghua; Liu, Yang; Wang, Hui; Ma, Li; Xia, Hechun; Niu, Jianguo; Sun, Tao; Zhang, Li

    2017-07-17

    The aim of this study was to clarify the protective role of taurine in neuronal apoptosis and the role of the Wnt/PCP-Jnk pathway in mediating the preventive effects of taurine on neural tube defects (NTDs). HT-22 cells (a hippocampal neuron cell line) were divided into a control group, a glutamate-induced apoptosis group, and glutamate (4.0 mmol/L) plus low-dose taurine (L; 0.5 mmol/L) and high-dose taurine (H; 2.0 mmol/L) groups. The MTT assay was used to monitor cell proliferation and cell survival. Immunofluorescence and Western blot analyses were used to determine caspase 9 expression. Retinoic acid (RA) induced embryonic NTDs in Kunming mice, thus establishing an NTD model. Pregnant mice were divided into a control group, an RA (30 mg/kg body weight) group, and an RA (30 mg/kg body weight) plus taurine (free drinking of 2 g/L solution) group. Immunohistochemistry and Western blot analyses were used to detect the expression of Dvl, RhoA and phosphorylated (p)-Jnk/Jnk in the embryonic neural tubes. In HT-22 cells, the apoptosis rate was significantly higher and caspase 9 activation was also significantly increased in the glutamate-induced apoptosis group compared to the L and H taurine groups. In the NTD model, the expression levels of Dvl, RhoA, and p-Jnk were significantly higher in the RA group than in the control group, whereas they were significantly reduced in the RA + taurine group. This study suggests that taurine has positive effects on neuronal protection and NTD prevention. Moreover, the Wnt/PCP-Jnk-dependent pathway plays an important role in taurine-mediated prevention of NTDs.

  8. Diagnosis of isolated high-grade prostatic intra-epithelial neoplasia: proposal of a nomogram for the prediction of cancer detection at saturation re-biopsy.

    PubMed

    Roscigno, Marco; Scattoni, Vincenzo; Freschi, Massimo; Abdollah, Firas; Maccagnano, Carmen; Galosi, Andrea; Lacetera, Vito; Montironi, Rodolfo; Muzzonigro, Giovanni; Deho, Federico; Deiana, Gianfranco; Belussi, Domenico; Chinaglia, Daniela; Montorsi, Francesco; Da Pozzo, Luigi F

    2012-05-01

    Study Type--Diagnostic (case series). Level of Evidence 4. What's known on the subject? And what does the study add? Multifocality, age, PSA values, and biopsy protocols regarding the predictive value of high grade PIN have been discussed extensively in the literature. Our study developed for the first time a predictive nomogram that could be helpful for patient counselling and to guide the urologist to perform rPBX after an initial diagnosis of isolated HGPIN. • To evaluate factors that may predict prostate cancer (PCa) detection after the initial diagnosis of high-grade prostatic intra-epithelial neoplasia (HGPIN) on prostate biopsy (PBx) with six to 24 random cores. • We retrospectively evaluated 262 patients submitted from 1998 to 2007 to prostate re-biopsy (rPBx) after an initial HGPIN diagnosis in tertiary academic centres. • HGPIN diagnosis was obtained on initial systematic PBx with six to 24 random cores. • All patients were re-biopsied with a 'saturation' rPBx with 20-26 cores, with a median time to rPBx of 12 months. • All slides were reviewed by expert uropathologists. • Plurifocal HGPIN (pHGPIN) was found in 115 patients and monofocal HGPIN (mHGPIN) was found in 147 patients. • In total, 108 and 154 patients, respectively, were submitted to >12-core initial PBx and ≤12-core initial PBx. • Overall PCa detection at rPBx was 31.7%. PSA level (7.7 vs 6.6 ng/mL; P= 0.031) and age (68 vs 64 years; P= 0.001) were significantly higher in patients with PCa at rPBx. • PCa detection was significantly higher in patients with a ≤12-core initial PBx than in those with a >12-core initial PBx (37.6% vs 23.1%; P= 0.01), as well as in patients with pHGPIN than in those with mHGPIN (40% vs 25.1%; P= 0.013). • At multivariable analysis, PSA level (P= 0.041; hazards ratio, HR, 1.08), age (P < 0.001; HR, 1.09), pHGPIN (P= 0.031; HR, 1.97) and ≤12-core initial PBx (P= 0.012; HR, 1.95) were independent predictors of PCa detection. • A nomogram

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

    PubMed

    Wang, Xiaofei; Xu, Dongliang; Liao, Yueling; Zhong, Shuangshuang; Song, Hongyong; Sun, Beibei; Zhou, Binhua P; Deng, Jiong; Han, Baohui

    2015-11-24

    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.

  10. Common alleles of predisposition in endocrine neoplasia.

    PubMed

    Eng, Charis

    2010-06-01

    The identification of germline high penetrance gain-of-function mutations in the RET proto-oncogene as causative of multiple endocrine neoplasia led to accurate molecular diagnosis, predictive testing and gene-informed preventative medicine. Many syndromic endocrine neoplasias fell under this clinically utile model, although not all endocrine neoplasias were accounted for by these high penetrance predisposition genes associated with the validated practice of clinical cancer genetics. The past decade has seen the identification of low penetrance alleles for various endocrine neoplasias, including medullary and epithelial thyroid carcinomas and isolated pituitary adenomas. Functional characterisation of these effects, which range from subtle expressional or micro-RNA regulation, and the analysis of the conferred risks, which are typically low and below the threshold for medical actionability, remain scientific challenges before these may be incorporated into routine clinical practice.

  11. Neoplasia: the second decade.

    PubMed

    Rehemtulla, Alnawaz

    2008-12-01

    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.

  12. 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

  13. Increased detection of Barrett's esophagus-associated neoplasia using wide-area trans-epithelial sampling: a multicenter, prospective, randomized trial.

    PubMed

    Vennalaganti, Prashanth R; Kaul, Vivek; Wang, Kenneth K; Falk, Gary W; Shaheen, Nicholas J; Infantolino, Anthony; Johnson, David A; Eisen, Glenn; Gerson, Lauren B; Smith, Michael S; Iyer, Prasad G; Lightdale, Charles J; Schnoll-Sussman, Felice; Gupta, Neil; Gross, Seth A; Abrams, Julian; Haber, Gregory B; Chuttani, Ram; Pleskow, Douglas K; Kothari, Shivangi; Goldblum, John R; Zhang, Yaxia; Sharma, Prateek

    2017-07-27

    Wide-area transepithelial sampling (WATS) with computer-assisted 3-dimensional analysis is a sampling technique that combines abrasive brushing of the Barrett's esophagus (BE) mucosa followed by neural network analysis to highlight abnormal-appearing cells. We performed a randomized trial of referred BE patients undergoing surveillance at 16 medical centers. Subjects received either biopsy sampling followed by WATS or WATS followed by biopsy sampling. The primary outcome was rate of detection of high-grade dysplasia/esophageal adenocarcinoma (HGD/EAC) using WATS in conjunction with biopsy sampling compared with biopsy sampling alone using standard histopathologic criteria. Secondary aims included evaluating neoplasia detection rates based on the procedure order (WATS vs biopsy sampling first), of each procedure separately, and the additional time required for WATS. One hundred sixty patients (mean age, 63.4 years; 76% men; 95% white) completed the trial. The median circumferential and maximal BE extents were 1.0 cm (interquartile range: .0-5.0) and 4.0 cm (interquartile range, 2.0-8.0), respectively. The diagnostic yield for biopsy sampling alone was as follows: HGD/EAC, 7 (4.4%); low-grade dysplasia (LGD), 28 (17.5%); nondysplastic BE (NDBE), 106 (66.25%); and no BE, 19 (11.9%). The addition of WATS to biopsy sampling yielded an additional 23 cases of HGD/EAC (absolute increase, 14.4%; 95% confidence interval, 7.5%-21.2%). Among these 23 patients, 11 were classified by biopsy sampling as NDBE and 12 as LGD/indefinite for dysplasia (IND); 14 received biopsy sampling first and 9 WATS first (not significant) and most (n = 21; 91.7%) had a prior dysplasia history. WATS added an average of 4.5 minutes to the procedure. Results of this multicenter, prospective, randomized trial demonstrate that the use of WATS in a referral BE population increases the detection of HGD/EAC. (Clinical trial registration number: NCT03008980.). Copyright © 2017. Published by Elsevier Inc.

  14. 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.

  15. 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

  16. Widespread JNK-dependent alternative splicing induces a positive feedback loop through CELF2-mediated regulation of MKK7 during T-cell activation.

    PubMed

    Martinez, Nicole M; Agosto, Laura; Qiu, Jinsong; Mallory, Michael J; Gazzara, Matthew R; Barash, Yoseph; Fu, Xiang-Dong; Lynch, Kristen W

    2015-10-01

    Alternative splicing is prevalent among genes encoding signaling molecules; however, the functional consequence of differential isoform expression remains largely unknown. Here we demonstrate that, in response to T-cell activation, the Jun kinase (JNK) kinase MAP kinase kinase 7 (MKK7) is alternatively spliced to favor an isoform that lacks exon 2. This isoform restores a JNK-docking site within MKK7 that is disrupted in the larger isoform. Consistently, we show that skipping of MKK7 exon 2 enhances JNK pathway activity, as indicated by c-Jun phosphorylation and up-regulation of TNF-α. Moreover, this splicing event is itself dependent on JNK signaling. Thus, MKK7 alternative splicing represents a positive feedback loop through which JNK promotes its own signaling. We further show that repression of MKK7 exon 2 is dependent on the presence of flanking sequences and the JNK-induced expression of the RNA-binding protein CELF2, which binds to these regulatory elements. Finally, we found that ∼25% of T-cell receptor-mediated alternative splicing events are dependent on JNK signaling. Strikingly, these JNK-dependent events are also significantly enriched for responsiveness to CELF2. Together, our data demonstrate a widespread role for the JNK-CELF2 axis in controlling splicing during T-cell activation, including a specific role in propagating JNK signaling. © 2015 Martinez et al.; Published by Cold Spring Harbor Laboratory Press.

  17. NEOPLASIA IN SNAKES AT ZOO ATLANTA DURING 1992-2012.

    PubMed

    Page-Karjian, Annie; Hahne, Megan; Leach, Kate; Murphy, Hayley; Lock, Brad; Rivera, Samuel

    2017-06-01

    A retrospective study was conducted to review neoplasia of captive snakes in the Zoo Atlanta collection from 1992 to 2012. Of 255 snakes that underwent necropsy and histopathologic examination at Zoo Atlanta during the study period, 37 were observed with neoplasia at necropsy. In those 37 snakes, 42 neoplastic lesions of 18 primary cell types were diagnosed. Thirty-five of those neoplasms (83.3%) were malignant, and of those, 19 were of mesenchymal origin, whereas 14 were of epithelial origin. The median annual rate of neoplasia at necropsy was 12.5% (interquartile range = 2.8-19.5%) over the 21-yr study period. The mean estimated age at death for snakes with neoplasia was 13.2 yr (range, 1-24 yr). Investigating the incidence and clinical significance of neoplasia in captive snakes is vital for developing effective preventative and treatment regimes.

  18. Vaginal intraepithelial neoplasia: a therapeutical dilemma.

    PubMed

    Frega, Antonio; Sopracordevole, Francesco; Assorgi, Chiara; Lombardi, Danila; DE Sanctis, Vitaliana; Catalano, Angelica; Matteucci, Eleonora; Milazzo, Giusi Natalia; Ricciardi, Enzo; Moscarini, Massimo

    2013-01-01

    Vaginal intraepithelial neoplasia (VaIN) represents a rare and asymptomatic pre-neoplastic lesion. Its natural history and potential evolution into invasive cancer are uncertain. VaIN can occur alone or as a synchronous or metachronous lesion with cervical and vulvar HPV-related intra epithelial or invasive neoplasia. Its association with cervical intraepithelial neoplasia is found in 65% of cases, with vulvar intraepithelial neoplasia in 10% of cases, while for others, the association with concomitant cervical or vulvar intraepithelial neoplasias is found in 30-80% of cases. VaIN is often asymptomatic and its diagnosis is suspected in cases of abnormal cytology, followed by colposcopy and colposcopically-guided biopsy of suspicious areas. In the past, high-grade VaIN and multifocal VaIN have been treated by radical surgery, such as total or partial upper vaginectomy associated with hysterectomy and radiotherapy. The need to maintain the integrity of reproductive capacity has determined the transition from radical therapies to conservative ones, according to the different patients' characteristics.

  19. Expression of Ceramide Synthase 6 Transcriptionally Activates Acid Ceramidase in a c-Jun N-terminal Kinase (JNK)-dependent Manner*

    PubMed Central

    Tirodkar, Tejas S.; Lu, Ping; Bai, Aiping; Scheffel, Matthew J.; Gencer, Salih; Garrett-Mayer, Elizabeth; Bielawska, Alicja; Ogretmen, Besim; Voelkel-Johnson, Christina

    2015-01-01

    A family of six ceramide synthases with distinct but overlapping substrate specificities is responsible for generation of ceramides with acyl chains ranging from ∼14–26 carbons. Ceramide synthase 6 (CerS6) preferentially generates C14- and C16-ceramides, and we have previously shown that down-regulation of this enzyme decreases apoptotic susceptibility. In this study, we further evaluated how increased CerS6 expression impacts sphingolipid composition and metabolism. Overexpression of CerS6 in HT29 colon cancer cells resulted in increased apoptotic susceptibility and preferential generation of C16-ceramide, which occurred at the expense of very long chain, saturated ceramides. These changes were also reflected in sphingomyelin composition. HT-CerS6 cells had increased intracellular levels of sphingosine, which is generated by ceramidases upon hydrolysis of ceramide. qRT-PCR analysis revealed that only expression of acid ceramidase (ASAH1) was increased. The increase in acid ceramidase was confirmed by expression and activity analyses. Pharmacological inhibition of JNK (SP600125) or curcumin reduced transcriptional up-regulation of acid ceramidase. Using an acid ceramidase promoter driven luciferase reporter plasmid, we demonstrated that CerS1 has no effect on transcriptional activation of acid ceramidase and that CerS2 slightly but significantly decreased the luciferase signal. Similar to CerS6, overexpression of CerS3–5 resulted in an ∼2-fold increase in luciferase reporter gene activity. Exogenous ceramide failed to induce reporter activity, while a CerS inhibitor and a catalytically inactive mutant of CerS6 failed to reduce it. Taken together, these results suggest that increased expression of CerS6 can mediate transcriptional activation of acid ceramidase in a JNK-dependent manner that is independent of CerS6 activity. PMID:25839235

  20. Expression of Ceramide Synthase 6 Transcriptionally Activates Acid Ceramidase in a c-Jun N-terminal Kinase (JNK)-dependent Manner.

    PubMed

    Tirodkar, Tejas S; Lu, Ping; Bai, Aiping; Scheffel, Matthew J; Gencer, Salih; Garrett-Mayer, Elizabeth; Bielawska, Alicja; Ogretmen, Besim; Voelkel-Johnson, Christina

    2015-05-22

    A family of six ceramide synthases with distinct but overlapping substrate specificities is responsible for generation of ceramides with acyl chains ranging from ∼14-26 carbons. Ceramide synthase 6 (CerS6) preferentially generates C14- and C16-ceramides, and we have previously shown that down-regulation of this enzyme decreases apoptotic susceptibility. In this study, we further evaluated how increased CerS6 expression impacts sphingolipid composition and metabolism. Overexpression of CerS6 in HT29 colon cancer cells resulted in increased apoptotic susceptibility and preferential generation of C16-ceramide, which occurred at the expense of very long chain, saturated ceramides. These changes were also reflected in sphingomyelin composition. HT-CerS6 cells had increased intracellular levels of sphingosine, which is generated by ceramidases upon hydrolysis of ceramide. qRT-PCR analysis revealed that only expression of acid ceramidase (ASAH1) was increased. The increase in acid ceramidase was confirmed by expression and activity analyses. Pharmacological inhibition of JNK (SP600125) or curcumin reduced transcriptional up-regulation of acid ceramidase. Using an acid ceramidase promoter driven luciferase reporter plasmid, we demonstrated that CerS1 has no effect on transcriptional activation of acid ceramidase and that CerS2 slightly but significantly decreased the luciferase signal. Similar to CerS6, overexpression of CerS3-5 resulted in an ∼2-fold increase in luciferase reporter gene activity. Exogenous ceramide failed to induce reporter activity, while a CerS inhibitor and a catalytically inactive mutant of CerS6 failed to reduce it. Taken together, these results suggest that increased expression of CerS6 can mediate transcriptional activation of acid ceramidase in a JNK-dependent manner that is independent of CerS6 activity.

  1. Oxidative stress promotes JNK-dependent amyloidogenic processing of normally expressed human APP by differential modification of alpha-, beta- and gamma-secretase expression.

    PubMed

    Quiroz-Baez, Ricardo; Rojas, Emilio; Arias, Clorinda

    2009-12-01

    The pathogenesis of Alzheimer disease (AD) is complex and is certain to involve diverse etiological factors, but a central role has been strongly suggested for amyloid beta-protein (Abeta), based on genetic, biochemical and neurotoxicological evidence. In contrast with the well-documented effect of genetic mutations in Abeta overproduction, not much is known about the mechanisms involved in sporadic AD (SAD) which account for more than 95% of cases. Extensive data from patients and in vivo animal models indicate that oxidative stress is one of the cardinal factors most frequently associated with this neurodegenerative disease. The aim of the present study was to explore the effect of oxidative stress on the normally expressed wild-type amyloid precursor protein (APP) in human neuroblastoma cells, which represents a more physiological model of neuronal Abeta generation. Since H(2)O(2) is the main source of the highly reactive hydroxyl radical in the brain, and FeCl(2) can stimulate oxidative stress, including the formation of the hydroxyl radical from H(2)O(2), in the present work we studied the effect of these two pro-oxidant molecules on the levels and processing of human APP by alpha-, beta- and gamma-secretase, and the role of the stress-activated kinase c-jun N-terminal kinase (JNK). We provide evidence for a dual modulation of amyloid precursor protein metabolism in differentiated human neuroblastoma cells related with a down-regulation of alpha-secretase and up-regulation of gamma-secretase, and particularly of beta-secretase and also a JNK depending Abeta generation.

  2. Cervical Neoplasia Probe Control

    SciTech Connect

    Vargo, Timothy D.

    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)

  3. TLR4 knockout attenuated high fat diet-induced cardiac dysfunction via NF-κB/JNK-dependent activation of autophagy.

    PubMed

    Hu, Nan; Zhang, Yingmei

    2017-08-01

    Obesity is commonly associated with a low grade systemic inflammation, which may contribute to the onset and development of myocardial remodeling and contractile dysfunction. Toll-like receptor 4 (TLR4) plays an important role in innate immunity and inflammation although its role in high fat diet-induced obesity cardiac dysfunction remains elusive. This study was designed to examine the effect of TLR4 ablation on high fat diet intake-induced cardiac anomalies, if any, and underlying mechanism(s) involved. Wild-type (WT) and TLR4 knockout mice were fed normal or high fat (60% calorie from fat) diet for 12weeks prior to assessment of mechanical and intracellular Ca(2+) properties. The inflammatory signaling proteins (TLR4, NF-κB, and JNK) and autophagic markers (Atg5, Atg12, LC3B and p62) were evaluated. Our results revealed that high fat diet intake promoted obesity, marked decrease in fractional shortening, and cardiomyocyte contractile capacity with dampened intracellular Ca(2+) release and clearance, elevated ROS generation and oxidative stress as measured by aconitase activity, the effects of which were significantly attenuated by TLR4 knockout. In addition, high fat intake downregulated levels of Atg5, Atg12 and LC3B, while increasing p62 accumulation. TLR4 knockout itself did not affect Atg5, Atg12, LC3B and p62 levels while it reconciled high fat diet intake-induced changes in autophagy. In addition, TLR4 knockout alleviated high fat diet-induced phosphorylation of IKKβ, JNK and mTOR. In vitro study revealed that palmitic acid suppressed cardiomyocyte contractile function, the effect of which was inhibited the TLR4 inhibitor CLI-095, the JNK inhibitor AS601245 or the NF-κB inhibitor Celastrol. Taken together, these data showed that TLR4 knockout ameliorated high fat diet-induced cardiac contractile and intracellular Ca(2+) anomalies through inhibition of inflammation and ROS, possibly through a NF-κB/JNK-dependent activation of autophagy. This article is

  4. Neoplasia after ureterosigmoidostomy.

    PubMed

    Azimuddin, K; Khubchandani, I T; Stasik, J J; Rosen, L; Riether, R D

    1999-12-01

    The occurrence of neoplasia after ureterosigmoidostomy is well-documented in the literature. Because of its rarity, few general surgeons will gain significant exposure to this entity, and colorectal surgeons are likely to be involved with the care of these patients. The purpose of this article is to apprise colorectal surgeons about the management of neoplasia after ureterosigmoidostomy and to familiarize them with the unique anatomy of the reconstructed pelvis. We performed a MEDLINE search to identify articles on ureterosigmoid tumors. The theories regarding the cause and pathology of these tumors were critically analyzed. A consensus was developed for screening patients with ureterosigmoidostomy and for treatment of neoplasia. The incidence of carcinoma after ureterosigmoidostomy ranges from 2 to 15 percent. Polyps are more common, and it seems that these tumors also follow the sequence of adenocarcinoma that is seen in the common variety of colorectal neoplasia. Neoplastic changes begin with the interaction of urine and feces and the healing colonic mucosa. Both production of nitrosamines by the action of bacteria on urine and DNA damage caused by reactive oxygen radicals produced by neutrophils at the healing anastomosis have been implicated in the pathogenesis of neoplasia. The latent period between formation of ureterosigmoidostomy and the appearance of carcinoma is between 20 and 26 years. Obstructive urinary symptoms that develop more than two years after ureterosigmoidostomy should be viewed with suspicion. The patient should be investigated with a CT scan and colonoscopy, and a barium enema may be required to delineate the anatomy further. If a benign tumor is encountered during colonoscopy, it may be removed by snare polypectomy. For a malignant tumor the segment of colon with ureteric implants should be excised, along with its lymphatic drainage. Bowel continuity is restored primarily, and the ureters are implanted in an ileal conduit. Patients with

  5. Lobular neoplasia: morphology and management.

    PubMed

    Jorns, Julie; Sabel, Michael S; Pang, Judy C

    2014-10-01

    Lobular neoplasia encompasses a spectrum of disease, including atypical lobular hyperplasia and lobular carcinoma in situ. Although classic forms of lobular neoplasia are predominantly heralded as a risk marker, the pleomorphic form of lobular carcinoma in situ is generally regarded as a more aggressive subtype and a possible cancer precursor, and thus is treated in a manner more similar to ductal carcinoma in situ than classic forms of lobular neoplasia. To focus on the morphologic spectrum of lobular neoplasia as highlighted by 3 cases and current management recommendations. Areas of diagnostic challenge and controversy are addressed. A review of the pertinent published literature and current national guidelines was conducted. Correct classification of classic lobular neoplasia and pleomorphic lobular carcinoma in situ is critical because of differences in clinical management, with current treatment strategies focused on risk reduction for patients with classic lobular neoplasia and eradication of the lesion for those with pleomorphic lobular carcinoma in situ.

  6. Human papillomavirus-associated oral intraepithelial neoplasia.

    PubMed

    Woo, Sook-Bin; Cashman, Emma C; Lerman, Mark A

    2013-10-01

    This study evaluated an unusual subset of oral epithelial dysplasia for the presence of transcriptionally active high-risk HPV subtypes and to further characterize the histological criteria for this condition. There were 20 cases diagnosed as epithelial dysplasia with marked apoptosis of the anterior oral cavity. Clinical and follow-up data were collected and histopathological features were documented. Immunoperoxidase studies were performed for p16 and in situ hybridization studies were performed for low- and high-risk HPV sub-types. Gender- and site-matched controls of conventional moderate-to-severe oral epithelial dysplasia were similarly evaluated using immunoperoxidase studies for p16 and in situ hybridization; the number of apoptotic cells for study and control cases was counted at two different tissue sites. There were 17 men and 3 women with a median age of 56 years. Seventeen lesions were described as white and five were described as rough or papillary. Thirteen were located on the lateral or ventral tongue, some extending onto the floor of the mouth. Epithelial hyperplasia with marked karyorrhexis and apoptosis were present in all the cases, along with features of conventional oral epithelial dysplasia. A statistically significant number of apoptotic cells were identified in the study cases when compared with controls (P>0.0001). Twenty cases were positive for high-risk HPV by in situ hybridization and all 19 nineteen cases evaluated for p16 demonstrated overexpression. Two patients were diagnosed with squamous cell carcinomas and one patient developed recurrent disease. We report a subset of oral epithelial dysplasia that occurs mostly in adult men on the ventral or lateral tongue and is positive for high-risk HPV and for p16. We propose use of the term 'HPV-associated Oral Intraepithelial Neoplasia' to characterize these lesions of the oral cavity for consistency in nomenclature with HPV-associated lesions of the lower anogenital tract. One case

  7. Multiple Endocrine Neoplasia Syndromes

    PubMed Central

    Pont, Allan

    1980-01-01

    The multiple endocrine neoplasia (MEN) syndromes consist of three distinct disease entities. They have in common adenomatous, carcinomatous or hyperplastic involvement of a variety of endocrine glands, and an autosomal dominant inheritance. MEN I includes hyperparathyroidism, islet cell and pituitary tumors. The components of MEN IIa are hyperparathyroidism, medullary thyroid carcinoma and pheochromocytoma. MEN IIb includes multiple neuromas, medullary thyroid carcinoma and pheochromocytoma. Effective tests are available for the early detection of components of the syndromes in potentially affected patients. Screening can lead to therapeutic intervention before clinical sequelae ensue. PMID:6247851

  8. CNP. Cervical Neoplasia Probe Control

    SciTech Connect

    Vargo, T.

    1995-05-17

    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)

  9. [Multiple endocrine neoplasia].

    PubMed

    Schaaf, Ludwig; Raue, Friedhelm

    2017-09-01

    Multiple endocrine neoplasia type 1 and 2 are hereditary cancer syndromes. They are characterized by the occurrence of many benign and malignant tumor types, in MEN1 parathyroid tumors, pituitary tumors, and pancreas tumors, in MEN2 medullary thyroid carcinoma, pheochromocytoma, and parathyroid tumors. The autosomal dominant inherited tumor syndromes are caused by mutations in the MEN1 gene, a tumor suppressor gene, and mutations in the RET gene, an activated oncogene, in MEN2. The clinical expression of the different tumors can vary within and between families, with a good genotype-phenotype correlation in MEN2. Early diagnosis and therapy is possible by using biochemical and imaging screening in the families. Early thyroidectomy in young patients with MEN2 results in a high cure rate of MTC. © Georg Thieme Verlag KG Stuttgart · New York.

  10. Human papillomavirus infection and other risk factors for cervical intraepithelial neoplasia in Japan

    PubMed Central

    Yoshikawa, H; Nagata, C; Noda, K; Nozawa, S; Yajima, A; Sekiya, S; Sugimori, H; Hirai, Y; Kanazawa, K; Sugase, M; Shimizu, H; Kawana, T

    1999-01-01

    Various risk factors were investigated in 167 cervical intra-epithelial neoplasia (CIN) case and control pairs in Japan. CIN cases showed evidence of nine known risk factors including smoking and sexual behaviour. However, after adjustment for papillomavirus infection, the highest determinant, the only remaining risk factors were: being married, early age at first pregnancy and multiparity. © 1999 Cancer Research Campaign PMID:10408876

  11. The biology of incipient, pre-invasive or intraepithelial neoplasia

    PubMed Central

    Grizzle, William E.; Srivastava, Sudhir; Manne, Upender

    2012-01-01

    pre-invasive neoplasia”, seems to best describe these putative pre-invasive lesions. Thus, terms such as incipient neoplasia should be abandoned. The term “intra-epithelial neoplasia” with an associated grade, which has been developed for pre-invasive neoplastic lesions of the cervix, i.e. cervical intraepithelial neoplasia (CIN), seems to be a terminology that adds consistency across epithelial organs. Thus, adoption of these terms for the additional organ sites of pancreas (PanIN) and prostate (PIN) seems accepted. Less descriptive terms such as the degrees of dysplasia of the oral cavity and bronchopulmonary system and actinic keratosis and Bowen's disease of the skin might be better designated as oral intraepithelial neoplasia (OIN), pulmonary intraepithelial neoplasia (PulIN) and dermal intraepithelial neoplasia (DIN). The etiology of pre-invasive neoplasia is the etiology of the matching cancers. Some obvious initiating factors include exposure to the whole range of ionizing and non-ionizing radiation, tobacco abuse and a broad range of other carcinogens (e.g., benzene). A frequent initiation factor is the setting of long standing continuing damage, inflammation and repair (LOCDIR) which leads to early molecular features associated with neoplasia after about one year. An excellent example of this is ulcerative colitis (UC) in which dysregulation of microsatellite repair enzymes have been documented one year following diagnosis of UC. While the nomenclature, description, diagnosis and etiology of pre-invasive neoplasia has advanced, approaches to therapy of such lesions have not progressed adequately even though it has been identified that, for example, removal of polyps periodically from the colorectum, DCIS from the breast, and high grade CIN from the cervix, results in a reduction in the development of cancers of the colorectum, breast, and cervix, respectively. With the development of more molecularly targeted therapy with fewer side effects, preventive therapies may be

  12. 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.

  13. 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.

  14. 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

  15. Pulmonary preinvasive neoplasia

    PubMed Central

    Kerr, K

    2001-01-01

    Advances in molecular biology have increased our knowledge of the biology of preneoplastic lesions in the human lung. The recently published WHO lung tumour classification defines three separate lesions that are regarded as preinvasive neoplasia. These are (1) squamous dysplasia and carcinoma in situ (SD/CIS), (2) atypical adenomatous hyperplasia (AAH), and (3) diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH). SD/CIS is graded in four stages (mild, moderate, severe, and CIS), based upon the distribution of atypical cells and mitotic figures. Most airways showing SD/CIS demonstrate a range of grades; many epithelia are hard to assess and the reproducibility of this complex system remains to be established. Detailed criteria are, however, welcome and provide an objective framework on which to compare various molecular changes. Alterations in gene expression and chromosome structure known to be associated with malignant transformation can be demonstrated in CIS, less so in dysplasias, but also in morphologically normal epithelium. The changes might be sequential, and their frequency and number increase with atypia. Less is known of the "risk of progression" of SD/CIS to invasive "central" bronchial carcinoma. It may take between one and 10 years for invasion to occur, yet the lesion(s) may be reversible if carcinogen exposure ceases. AAH may be an important precursor lesion for peripheral "parenchymal" adenocarcinoma of the lung: the "adenoma" in an adenoma–carcinoma sequence. There is good morphological evidence that AAH may progress from low to high grade to bronchioloalveolar carcinoma (BAC; a non-invasive lesion by definition). Invasion then develops within BAC and peripheral lung adenocarcinoma evolves. The molecular events associated with this progression are not well understood and studies are hampered by a lack of clear criteria to distinguish high grade AAH from BAC. Nonetheless, as with SD/CIS, the patterns of expression of tumour

  16. 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.

  17. 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.

  18. 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

  19. 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.

    PubMed

    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 1.011μg Cd per cigarette equivalent, and Cd (0.0003μg Cd/1×10(7) cells) was also detected in the lysates from MCF-10A cells treated with 25μg/mL CSC. In similar manner to CSC, CdCl2 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 CdCl2 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. © 2013.

  20. Optical coherence tomography in vulvar intraepithelial neoplasia

    NASA Astrophysics Data System (ADS)

    Wessels, Ronni; de Bruin, Daniel M.; Faber, Dirk J.; van Boven, Hester H.; Vincent, Andrew D.; van Leeuwen, Ton G.; van Beurden, Marc; Ruers, Theo J. M.

    2012-11-01

    Vulvar squamous cell carcinoma (VSCC) is a gynecological cancer with an incidence of two to three per 100,000 women. VSCC arises from vulvar intraepithelial neoplasia (VIN), which is diagnosed through painful punch biopsy. In this study, optical coherence tomography (OCT) is used to differentiate between normal and VIN tissue. We hypothesize that (a) epidermal layer thickness measured in OCT images is different in normal tissue and VIN, and (b) quantitative analysis of the attenuation coefficient (μoct) extracted from OCT data differentiates VIN from normal vulvar tissue. Twenty lesions from 16 patients are imaged with OCT. Directly after data acquisition, a biopsy is performed. Epidermal thickness is measured and values of μoct are extracted from 200 OCT scans of normal and VIN tissue. For both methods, statistical analysis is performed using Paired Mann-Whitney-test. Correlation between the two methods is tested using a Spearman-correlation test. Both epidermal layer thickness as well as the μoct are different between normal vulvar tissue and VIN lesions (p<0.0001). Moreover, no correlation is found between the epidermal layer thickness and μoct. This study demonstrates that both the epidermal thickness and the attenuation coefficient of vulvar epithelial tissue containing VIN are different from that of normal vulvar tissue.

  1. Quantitative architectural analysis of bronchial intraepithelial neoplasia

    NASA Astrophysics Data System (ADS)

    Guillaud, Martial; MacAulay, Calum E.; Le Riche, Jean C.; Dawe, Chris; Korbelik, Jagoda; Lam, Stephen

    2000-04-01

    Considerable variation exists among pathologist in the interpretation of intraepithelial neoplasia making it difficult to determine the natural history of these lesion and to establish management guidelines for chemoprevention. The aim of the study is to evaluate architectural features of pre-neoplastic progression in lung cancer, and to search for a correlation between architectural index and conventional pathology. Quantitative architectural analysis was performed on a series of normal lung biopsies and Carcinoma In Situ (CIS). Centers of gravity of the nuclei within a pre-defined region of interest were used as seeds to generate a Voronoi Diagram. About 30 features derived from the Voronoi diagram, its dual the Delaunay tessellation, and the Minimum Spanning Tree were extracted. A discriminant analysis was performed to separate between the two groups. The architectural Index was calculated for each of the bronchial biopsies that were interpreted as hyperplasia, metaplasia, mild, moderate or severe dysplasia by conventional histopathology criteria. As a group, lesions classified as CIS by conventional histopathology criteria could be distinguished from dysplasia using the architectural Index. Metaplasia was distinct from hyperplasia and hyperplasia from normal. There was overlap between severe and moderate dysplasia but mild dysplasia could be distinguished form moderate dysplasia. Bronchial intraepithelial neoplastic lesions can be degraded objectively by architectural features. Combination of architectural features and nuclear morphometric features may improve the quantitation of the changes occurring during the intra-epithelial neoplastic process.

  2. Surgery for cervical intraepithelial neoplasia

    PubMed Central

    Martin-Hirsch, Pierre PL; Paraskevaidis, Evangelos; Bryant, Andrew; Dickinson, Heather O; Keep, Sarah L

    2014-01-01

    Background Cervical intraepithelial neoplasia (CIN) is the most common pre-malignant lesion. Atypical squamous changes occur in the transformation zone of the cervix with mild, moderate or severe changes described by their depth (CIN 1, 2 or 3). Cervical intraepithelial neoplasia is treated by local ablation or lower morbidity excision techniques. Choice of treatment depends on the grade and extent of the disease. Objectives To assess the effectiveness and safety of alternative surgical treatments for CIN. Search methods We searched the Cochrane Gynaecological Cancer Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE and EMBASE (up to April 2009). We also searched registers of clinical trials, abstracts of scientific meetings and reference lists of included studies. Selection criteria Randomised controlled trials (RCTs) of alternative surgical treatments in women with cervical intraepithelial neoplasia. Data collection and analysis Two review authors independently abstracted data and assessed risks of bias. Risk ratios that compared residual disease after the follow-up examination and adverse events in women who received one of either laser ablation, laser conisation, large loop excision of the transformation zone (LLETZ), knife conisation or cryotherapy were pooled in random-effects model meta-analyses. Main results Twenty-nine trials were included. Seven surgical techniques were tested in various comparisons. No significant differences in treatment failures were demonstrated in terms of persistent disease after treatment. Large loop excision of the transformation zone appeared to provide the most reliable specimens for histology with the least morbidity. Morbidity was lower than with laser conisation, although the trials did not provide data for every outcome measure. There were not enough data to assess the effect on morbidity when compared with laser ablation. Authors’ conclusions The evidence

  3. Diabetes Mellitus and Colorectal Neoplasia

    PubMed Central

    Acevedo, Alejandro; Diaz, Yaritza; Perez, Cynthia M.; Garau, Maria; Baron, John

    2012-01-01

    Background Many studies have provided evidence for an association between obesity, physical inactivity, and western diet as risk factors for colorectal cancer (CRC). Few studies directly address the association between type 2 Diabetes Mellitus (DM) and the risk of colorectal lesions at specific anatomic locations. Methods 2,663 subjects with a previous history of adenoma(s) and removal of all current adenomas at study entry were followed for a mean time of three years across three different chemoprevention clinical trials. The primary endpoint was colorectal adenoma recurrence and number of lesions during the treatment phase; the secondary endpoints were presence of advanced colorectal neoplasia (CRN) and location of CRN. Using log linear regression, the effect of DM status on the relative risk (RR) of CRN recurrence, advanced CRN, and location of CRN was assessed. Results DM status was not significantly associated with incidence of colorectal adenomas, incidence of advanced colorectal lesions, or left-sided colorectal neoplastic lesions. Subjects with DM had a marginally increased risk of right-sided (p= 0.06) colorectal adenomas and a significant increased risk of multiple right-sided adenomas (p=0.03) in the unadjusted model; this association was not significant after adjusting for age and other potential confounders (RR=1.22, 95% CI: 0.85–1.76). Conclusion We did not observe a statistically significant increased risk in CRN recurrence for overall neoplasia, advanced neoplasia or location of neoplasia in individuals with DM compared to non-DM individuals. However, given the patterns observed in this investigation, future studies with longer follow-up time and longer DM exposure, incorporating objective measurements of type 2 DM might help elucidate the risk of CRN among individuals with DM. PMID:23560242

  4. 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

  5. Human papillomavirus infection and induction of neoplasia: a matter of fitness.

    PubMed

    Kranjec, Christian; Doorbar, John

    2016-10-01

    The aetiologic association between infection with certain human papillomavirus (HPV) types, high-grade squamous neoplasia, and cancer at different epithelial sites is well established. In this review we briefly discuss recent breakthroughs in the regulation of squamous epithelia in homeostasis and disease, and provide a view of how these discoveries modify our understanding of how HPV-induced neoplasia in squamous epithelia is triggered. Taken together, these observations highlight how HPVs have evolved the ability to inactivate the products of genes that are frequently mutated in non-HPV-associated pre-neoplasia and squamous cell carcinoma of sun-exposed skin, and introduce a Darwinian model of clonal evolution of HPV-infected cells. These concepts are considered against our current understanding of transformation zones where HPV-associated cancers occur more frequently, and other sites of non-productive (or abortive) HPV infection.

  6. Antioxidant Prophylaxis in the Prevention of Prostatic Epithelial Neoplasia

    DTIC Science & Technology

    2007-02-01

    lycopene , β-carotene etc. have been found to be effective in lowering prostate cancer risk. Although these data suggest the importance of oxidative...Decreased expression of endogenous antioxidant enzymes is associated with PIN and prostate cancer (5). Antioxidants such as vitamin E, selenium and lycopene ...have been shown to inhibit growth of prostate cancer cells in culture (6-10). Recently administration of vitamin E, selenium, and lycopene was shown

  7. Prostaglandin E2-induced colonic secretion in patients with and without colorectal neoplasia

    PubMed Central

    2010-01-01

    Background The pathogenesis for colorectal cancer remains unresolved. A growing body of evidence suggests a direct correlation between cyclooxygenase enzyme expression, prostaglandin E2 metabolism and neoplastic development. Thus further understanding of the regulation of epithelial functions by prostaglandin E2 is needed. We hypothesized that patients with colonic neoplasia have altered colonic epithelial ion transport and express functionally different prostanoid receptor levels in this respect. Methods Patients referred for colonoscopy were included and grouped into patients with and without colorectal neoplasia. Patients without endoscopic findings of neoplasia served as controls. Biopsy specimens were obtained from normally appearing mucosa in the sigmoid part of colon. Biopsies were mounted in miniaturized modified Ussing air-suction chambers. Indomethacin (10 μM), various stimulators and inhibitors of prostanoid receptors and ion transport were subsequently added to the chamber solutions. Electrogenic ion transport parameters (short circuit current and slope conductance) were recorded. Tissue pathology and tissue damage before and after experiments was assessed by histology. Results Baseline short circuit current and slope conductance did not differ between the two groups. Patients with neoplasia were significantly more sensitive to indomethacin with a decrease in short circuit current of 15.1 ± 2.6 μA·cm-2 compared to controls, who showed a decrease of 10.5 ± 2.1 μA·cm-2 (p = 0.027). Stimulation or inhibition with theophylline, ouabain, bumetanide, forskolin or the EP receptor agonists prostaglandin E2, butaprost, sulprostone and prostaglandin E1 (OH) did not differ significantly between the two groups. Histology was with normal findings in both groups. Conclusions Epithelial electrogenic transport is more sensitive to indomethacin in normal colonic mucosa from patients with previous or present colorectal neoplasia compared to colonic mucosa from

  8. 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.

  9. Esophagectomy for Superficial Esophageal Neoplasia.

    PubMed

    Watson, Thomas J

    2017-07-01

    Endoscopic therapies have become the standard of care for most cases of Barrett's esophagus with high-grade dysplasia or intramucosal adenocarcinoma. Despite a rapid and dramatic evolution in treatment paradigms, esophagectomy continues to occupy a place in the therapeutic armamentarium for superficial esophageal neoplasia. The managing physician must remain cognizant of the limitations of endoscopic approaches and consider surgical resection when they are exceeded. Esophagectomy, performed at experienced centers for appropriately selected patients with early-stage disease can be undertaken with the expectation of cure as well as low mortality, acceptable morbidity, and good long-term quality of life. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. 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.

  11. Transporter function and cyclic AMP turnover in normal colonic mucosa from patients with and without colorectal neoplasia.

    PubMed

    Kleberg, Karen; Jensen, Gerda Majgaard; Christensen, Dan Ploug; Lundh, Morten; Grunnet, Lars Groth; Knuhtsen, Svend; Poulsen, Steen Seier; Hansen, Mark Berner; Bindslev, Niels

    2012-06-26

    The pathogenesis of colorectal neoplasia is still unresolved but has been associated with alterations in epithelial clearance of xenobiotics and metabolic waste products. The aim of this study was to functionally characterize the transport of cyclic nucleotides in colonic biopsies from patients with and without colorectal neoplasia. Cyclic nucleotides were used as model substrates shared by some OATP- and ABC-transporters, which in part are responsible for clearance of metabolites and xenobiotics from the colonic epithelium. On colonic biopsies from patients with and without colorectal neoplasia, molecular transport was electrophysiologically registered in Ussing-chamber set-ups, mRNA level of selected transporters was quantified by rt-PCR, and subcellular location of transporters was determined by immunohistochemistry. Of four cyclic nucleotides, dibuturyl-cAMP induced the largest short circuit current in both patient groups. The induced short circuit current was significantly lower in neoplasia-patients (p = 0.024). The observed altered transport of dibuturyl-cAMP in neoplasia-patients could not be directly translated to an observed increased mRNA expression of OATP4A1 and OATP2B1 in neoplasia patients. All other examined transporters were expressed to similar extents in both patient groups. OATP1C1, OATP4A1, OATP4C1 seem to be involved in the excretory system of human colon. ABCC4 is likely to be involved from an endoplasmic-Golgi complex and basolateral location in goblet cells. ABCC5 might be directly involved in the turnover of intracellular cAMP at the basolateral membrane of columnar epithelial cells, while OATP2B1 is indirectly related to the excretory system. Colorectal neoplasia is associated with lower transport or sensitivity to cyclic nucleotides and increased expression of OATP2B1 and OATP4A1 transporters, known to transport PGE(2).

  12. Transporter function and cyclic AMP turnover in normal colonic mucosa from patients with and without colorectal neoplasia

    PubMed Central

    2012-01-01

    Background The pathogenesis of colorectal neoplasia is still unresolved but has been associated with alterations in epithelial clearance of xenobiotics and metabolic waste products. The aim of this study was to functionally characterize the transport of cyclic nucleotides in colonic biopsies from patients with and without colorectal neoplasia. Methods Cyclic nucleotides were used as model substrates shared by some OATP- and ABC-transporters, which in part are responsible for clearance of metabolites and xenobiotics from the colonic epithelium. On colonic biopsies from patients with and without colorectal neoplasia, molecular transport was electrophysiologically registered in Ussing-chamber set-ups, mRNA level of selected transporters was quantified by rt-PCR, and subcellular location of transporters was determined by immunohistochemistry. Results Of four cyclic nucleotides, dibuturyl-cAMP induced the largest short circuit current in both patient groups. The induced short circuit current was significantly lower in neoplasia-patients (p = 0.024). The observed altered transport of dibuturyl-cAMP in neoplasia-patients could not be directly translated to an observed increased mRNA expression of OATP4A1 and OATP2B1 in neoplasia patients. All other examined transporters were expressed to similar extents in both patient groups. Conclusions OATP1C1, OATP4A1, OATP4C1 seem to be involved in the excretory system of human colon. ABCC4 is likely to be involved from an endoplasmic-Golgi complex and basolateral location in goblet cells. ABCC5 might be directly involved in the turnover of intracellular cAMP at the basolateral membrane of columnar epithelial cells, while OATP2B1 is indirectly related to the excretory system. Colorectal neoplasia is associated with lower transport or sensitivity to cyclic nucleotides and increased expression of OATP2B1 and OATP4A1 transporters, known to transport PGE2. PMID:22734885

  13. 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.

  14. Dietary fibre and colonic neoplasia.

    PubMed Central

    Freeman, H J

    1979-01-01

    Dietary plant fibre, or plantix, is thought to play a significant role in the pathogenesis of colon cancer in humans. It is a complex polymeric substance that has several distinct components resistant to hydrolysis by the digestive enzymes of humans. These components include cellulose, hemicelluloses, pectins, lignin, gums, mucilages and, in certain instances, algal polysaccharides. These polymers have different physicochemical properties, and recent evidence from experimental studies in animals treated with carcinogens suggests that some may exert protective effects in the intestine and others may enhance colon carcinogenesis. This review synthesizes information on the chemical composition, methods of analysis and physicochemical properties of dietary plant fibre and reviews available studies examining the role of fibre in colonic neoplasia in animals and humans. PMID:466603

  15. Local management of rectal neoplasia.

    PubMed

    Touzios, John; Ludwig, Kirk A

    2008-11-01

    The treatment of rectal neoplasia, whether benign or malignant, challenges the surgeon. The challenge in treating rectal cancer is selecting the proper approach for the appropriate patient. In a small number of rectal cancer patients local excision may be the best approach. In an attempt to achieve two goals-cure of disease with a low rate of local failure and maintenance of function and quality of life-multiple approaches can be utilized. The key to obtaining a good outcome for any one patient is balancing the competing factors that impact on these goals. Any effective treatment aimed at controlling rectal cancer in the pelvis must take into account the disease in the bowel wall itself and the disease, or potential disease, in the mesorectum. The major downside of local excision techniques is the potential of leaving untreated disease in the mesorectum. Local management techniques avoid the potential morbidity, mortality, and functional consequences of a major abdominal radical resection and are thus quite effective in achieving the maintenance of function and quality of life goal. The issue for the transanal techniques is how they fare in achieving the first goal-cure of the cancer while keeping local recurrence rates to an absolute minimum. Without removing both the rectum and the mesorectum there is no completely accurate way to determine whether a rectal cancer has moved outside the bowel wall, so any decision on local management of a rectal neoplasm is a calculated risk. For benign neoplasia, the challenge is removing the lesion without having to resort to a major abdominal procedure.

  16. Keratin 17 Is a Prognostic Biomarker in Endocervical Glandular Neoplasia.

    PubMed

    Mockler, Daniel; Escobar-Hoyos, Luisa F; Akalin, Ali; Romeiser, Jamie; Shroyer, A Laurie; Shroyer, Kenneth R

    2017-09-01

    Previous work in our laboratory identified keratin 17 (K17) as a specific and sensitive biomarker for high-grade squamous intraepithelial lesions and cervical squamous cell carcinoma (SCC). K17, however, has not been previously evaluated in endocervical glandular neoplasia. Based on the similar pathogenesis of squamous and glandular lesions of the cervix, we hypothesized that K17 overexpression could also be a diagnostic and/or prognostic biomarker for endocervical neoplasia. Cases of endocervical adenocarcinoma (n = 90), adenocarcinoma in situ (AIS) (n = 32), benign glandular lesions (n = 36), and normal endocervical mucosa (n = 5) were selected from Stony Brook Medicine and the University of Massachusetts from 2002 to 2013. Immunohistochemical staining for K17 was performed by an indirect immunoperoxidase method and was scored based on the proportion of cells that showed strong (2+) staining. K17 was highly expressed in 21 (65.6%) of 32 AIS and in 75 (83.0%) of 90 adenocarcinoma cases. In adenocarcinomas, K17 staining was detected in a mean of 33.9% of malignant cells. Staining tended to be strongest at the periphery of pseudoglandular groups and at the invasive front of tumors. K17 was not detected in the epithelial cells of benign glandular lesions, but groups of cuboidal cells, residing beneath the epithelial layer of benign glands, were frequently positive for K17, especially in cases of microglandular hyperplasia. High levels of K17 expression were significantly associated with decreased patient survival. K17 is highly expressed in most cases of both invasive adenocarcinoma and in AIS and is a powerful, negative prognostic marker for patient survival.

  17. Lobular intraepithelial neoplasia arising within breast fibroadenoma.

    PubMed

    Limite, Gennaro; Esposito, Emanuela; Sollazzo, Viviana; Ciancia, Giuseppe; Formisano, Cesare; Di Micco, Rosa; De Rosa, Dario; Forestieri, Pietro

    2013-07-12

    Fibroadenomas are the second most common breast pathology occurring in young women under the age of 35 years old. Fibroadenomas can be classified as simple or complex according to histological features. Complex fibroadenomas differ from simple fibroadenomas because of the presence of cysts (3 mm), sclerosing adenosis, epithelial calcifications, or papillary apocrine changes. Most fibroadenomas are clinically identifiable. In 25% of cases, fibroadenomas are non-palpable and are diagnosed with mammography and ultrasound. Differential diagnosis with well differentiated breast cancer is often necessary, particularly with medullary or mucinous tumors. Calcification findings within fibroadenomas by mammogram have to be investigated. The age of a lump is usually reflected by calcifications. Microcalcification can hide foci of carcinoma in situ when they are small, branching type, and heterogeneous. However, many morphological possibilities may not be reliable for deciding whether a certain calcification is the product of a malignant or a benign process. From a radiological point of view, fibroadenomas containing foci of carcinoma in situ can be indistinguishable from benign lesions, even if the incidence of carcinoma within fibroadenomas is estimated as 0.1-0.3%, and it could be a long-term risk factor for invasive breast cancer. A 44-year-old woman presented with a 1.5-cm palpable, smooth, mobile lump in the lower-inner quadrant of her right breast. Standard mediolateral oblique and craniocaudal mammograms showed a cluster of eccentric popcorn-like calcifications within the fibroadenoma. After lumpectomy, a definitive histological examination confirmed the intra-operative diagnosis of a benign mass. However, lobular intraepithelial neoplasia foci were found, surrounded by atypical lobular hyperplasia. The possibility of an old benign breast lump might be supported by fine needle aspiration biopsy or core biopsy before initiating follow-up. According to our experience

  18. Lobular intraepithelial neoplasia arising within breast fibroadenoma

    PubMed Central

    2013-01-01

    Background Fibroadenomas are the second most common breast pathology occurring in young women under the age of 35 years old. Fibroadenomas can be classified as simple or complex according to histological features. Complex fibroadenomas differ from simple fibroadenomas because of the presence of cysts (3 mm), sclerosing adenosis, epithelial calcifications, or papillary apocrine changes. Most fibroadenomas are clinically identifiable. In 25% of cases, fibroadenomas are non-palpable and are diagnosed with mammography and ultrasound. Differential diagnosis with well differentiated breast cancer is often necessary, particularly with medullary or mucinous tumors. Calcification findings within fibroadenomas by mammogram have to be investigated. The age of a lump is usually reflected by calcifications. Microcalcification can hide foci of carcinoma in situ when they are small, branching type, and heterogeneous. However, many morphological possibilities may not be reliable for deciding whether a certain calcification is the product of a malignant or a benign process. From a radiological point of view, fibroadenomas containing foci of carcinoma in situ can be indistinguishable from benign lesions, even if the incidence of carcinoma within fibroadenomas is estimated as 0.1–0.3%, and it could be a long-term risk factor for invasive breast cancer. Case presentation A 44-year-old woman presented with a 1.5-cm palpable, smooth, mobile lump in the lower-inner quadrant of her right breast. Standard mediolateral oblique and craniocaudal mammograms showed a cluster of eccentric popcorn-like calcifications within the fibroadenoma. After lumpectomy, a definitive histological examination confirmed the intra-operative diagnosis of a benign mass. However, lobular intraepithelial neoplasia foci were found, surrounded by atypical lobular hyperplasia. Conclusions The possibility of an old benign breast lump might be supported by fine needle aspiration biopsy or core biopsy before initiating

  19. The significance of marked nuclear atypia in grade 1 cervical intraepithelial neoplasia.

    PubMed

    Fadare, Oluwole; Rodriguez, Rosemarie

    2009-10-01

    Approximately 10% to 15% of cases of grade 1 cervical intraepithelial neoplasia are found to have progressed to a high-grade squamous intraepithelial lesion or higher at follow-up, and there are presently no reliable morphological predictors of this subset. It has recently been reported that cases of grade 1 cervical intraepithelial neoplasia that display marked nuclear atypia (defined as cases with at least 5 epithelial cells with nuclear enlargement of at least 5 times the size of an intermediate cell, and/or multinucleation of at least 5 nuclei.) have a substantially higher rate of high-grade squamous intraepithelial lesion on short-term follow-up and may, therefore, require more aggressive initial management. We report herein our experience with a cohort of such cases. After a review of consecutive cervical biopsies, 352 cases with grade 1 cervical intraepithelial neoplasia were classified into group 1 (grade 1 cervical intraepithelial neoplasia with marked atypia, n = 31) and group 2 (grade 1 cervical intraepithelial neoplasia without marked atypia, n = 321). The average follow-up rates for groups 1 and 2 were 93.55% (29/31) and 90.65% (291/321), respectively. Average follow-up durations were 14.3 and 17.9 months, respectively. The follow-up high-grade squamous intraepithelial lesion rate of the cases with marked atypia was 10.34%, as compared with 11.68% for cases without marked atypia. The follow-up interpretive frequency (in cytologic samples) of "low-grade squamous intraepithelial lesion" was significantly higher in group 1(19/29 versus 114/291, P = .009). However, no significant differences were identified between groups 1 and 2 regarding the interpretive frequencies of either high-grade squamous intraepithelial lesion (3/29 versus 34/291, P = 1) or "negative for intraepithelial lesion or malignancy" (6/29 versus 56/291, P = .8) in follow-up cytologic samples. In subsets of both groups in which high-risk human papillomavirus testing was performed in the

  20. [Multiple endocrine neoplasia type 2].

    PubMed

    Krysiak, Robert; Okopień, Bogusław

    2012-04-01

    Multiple endocrine neoplasia type 2 syndrome (MEN-2) is a rare hereditary cancer syndrome with autosomal dominant trait of inheritance. The most characteristic feature of this syndrome is a complete penetrance of medullary thyroid cancer. On the basis of differences in variable expression of pheochromocytomas, hyperparathyroidism, and other clinical features, MEN-2 is divided into three clinical variants, referred to as MEN-2A, MEN-2B and familial medullary thyroid cancer. In the most frequent variant, MEN-2A syndrome, apart from thyroid carcinoma, this syndrome includes also unilateral or bilateral pheochromocytoma and hyperparathyroidism. In less common MEN-2B, medullary thyroid cancer and pheochromocytoma occur together with complex nervous and skeletal abnormalities. Familial medullary thyroid cancer is a variant of MEN-2 in which individuals affected develop only this neoplasm without other manifestations of MEN-2. It is well known that MEN-2 is caused by mutations of different codons of the RET proto-oncogene. The identification of mutations associated with this syndrome has led to genetic testing to identify patients at risk for MEN-2. There is a significant genotype-phenotype correlation, which allows a more individualised approach to the timing of prophylactic thyroidectomy. In this paper, we review the current views on the etiopathogenesis, clinical presentation, diagnosis and treatment of MEN-2.

  1. 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.

  2. Multiple endocrine neoplasia type I.

    PubMed

    Beukes, E; Dent, D M; De Villiers, J C; Miller, J L

    1985-08-17

    During the 13-year period 1970-1983 only 7 cases of multiple endocrine neoplasia type I (MEN I) were seen at Groote Schuur Hospital, suggesting that the associated gene is rare in this area. Only 1 of these patients was black. Endocrine associations were as follows: hyperparathyroidism--6 cases, pituitary hypersecretion--6 cases (3 each involving growth hormone and prolactin), and pancreatic hypersecretion--3 cases (2 of gastrinoma and 1 of insulinoma). The presenting features were predictably diverse and depended on the component which manifested first. There was little difficulty in reaching a diagnosis on routine investigation. All patients with hyperparathyroidism underwent a 3 1/2-gland parathyroidectomy as the first treatment procedure, normocalcaemia being achieved in 5 cases, but persistent hypercalcaemia in the 6th suggested a supernumerary gland. A pituitary adenoma was removed in 4 cases, but persistent prolactinaemia necessitated bromocriptine therapy in 3. Successful distal pancreatectomy was undertaken in a patient with insulinoma and a patient with gastrinoma, and a further patient with gastrinoma awaits surgery. The overall prognosis in cases of MEN I appears to depend on the most aggressive component, often the pancreatic lesion; our patients have run a surprisingly benign course with only 1 late death, from hypertensive heart disease.

  3. Invasive 3-Dimensional Organotypic Neoplasia from Multiple Normal Human Epithelia

    PubMed Central

    Ridky, Todd W.; Chow, Jennifer M.; Wong, David J.; Khavari, Paul A.

    2013-01-01

    Refined cancer models are required to assess the burgeoning number of potential targets for cancer therapeutics within a rapid and clinically relevant context. Here we utilize tumor-associated genetic pathways to transform primary human epithelial cells from epidermis, oropharynx, esophagus, and cervix into genetically defined tumors within a human 3-dimensional (3-D) tissue environment incorporating cell-populated stroma and intact basement membrane. These engineered organotypic tissues recapitulated natural features of tumor progression, including epithelial invasion through basement membrane, a complex process critically required for biologic malignancy in 90% of human cancers. Invasion was rapid, and potentiated by stromal cells. Oncogenic signals in 3-D tissue, but not 2-D culture, resembled gene expression profiles from spontaneous human cancers. Screening well-characterized signaling pathway inhibitors in 3-D organotypic neoplasia helped distil a clinically faithful cancer gene signature. Multi-tissue 3-D human tissue cancer models may provide an efficient and relevant complement to current approaches to characterize cancer progression. PMID:21102459

  4. Prevalence of neoplasia in 10 New England populations of the soft-shell clam (Mya arenaria).

    PubMed

    Brown, R S; Wolke, R E; Saila, S B; Brown, C W

    1978-09-29

    Neoplasia was a prevalent disease of the soft-shell clam and was found in widely geographically distinct sites in New England. Two types of neoplasms were recognized. Most were of hematopoietic origin, except in clams from Maine, which also had gonadal neoplasms. Both types were apparently malignant neoplasms, based on their characteristic anaplastic appearance, invasiveness, metastasis, mitotic activity, associated tissue necrosis, and mortality. Diagnosis of neoplasia in the living mollusk was achieved rapidly and accurately by cytologic examination of circulating blood. The etiology of the neoplasms was not identified. In general, nonneoplastic lesions, such as epithelial hyperplasia and accumulations of a orange-brown bodies, were more common in clams from polluted areas.

  5. Multiple endocrine neoplasia type 1

    PubMed Central

    Marini, Francesca; Falchetti, Alberto; Monte, Francesca Del; Sala, Silvia Carbonell; Gozzini, Alessia; Luzi, Ettore; Brandi, Maria Luisa

    2006-01-01

    Multiple Endocrine Neoplasia type 1 (MEN1) is a rare autosomal dominant hereditary cancer syndrome presented mostly by tumours of the parathyroids, endocrine pancreas and anterior pituitary, and characterised by a very high penetrance and an equal sex distribution. It occurs in approximately one in 30,000 individuals. Two different forms, sporadic and familial, have been described. The sporadic form presents with two of the three principal MEN1-related endocrine tumours (parathyroid adenomas, entero-pancreatic tumours and pituitary tumours) within a single patient, while the familial form consists of a MEN1 case with at least one first degree relative showing one of the endocrine characterising tumours. Other endocrine and non-endocrine lesions, such as adrenal cortical tumours, carcinoids of the bronchi, gastrointestinal tract and thymus, lipomas, angiofibromas, collagenomas have been described. The responsible gene, MEN1, maps on chromosome 11q13 and encodes a 610 aminoacid nuclear protein, menin, with no sequence homology to other known human proteins. MEN1 syndrome is caused by inactivating mutations of the MEN1 tumour suppressor gene. This gene is probably involved in the regulation of several cell functions such as DNA replication and repair and transcriptional machinery. The combination of clinical and genetic investigations, together with the improving of molecular genetics knowledge of the syndrome, helps in the clinical management of patients. Treatment consists of surgery and/or drug therapy, often in association with radiotherapy or chemotherapy. Currently, DNA testing allows the early identification of germline mutations in asymptomatic gene carriers, to whom routine surveillance (regular biochemical and/or radiological screenings to detect the development of MEN1-associated tumours and lesions) is recommended. PMID:17014705

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

    PubMed Central

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

    2015-01-01

    Abstract. 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. PMID:25950645

  7. 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.

  8. Fractal analysis of cervical intraepithelial neoplasia.

    PubMed

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

    2014-01-01

    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. 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. 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. Fractal dimension can be considered to be an objective parameter to grade cervical intraepithelial neoplasia.

  9. Treatment of ocular surface squamous neoplasia with Mitomycin C.

    PubMed

    Gupta, A; Muecke, J

    2010-05-01

    AIM To report the outcome of treatment of non-invasive ocular surface squamous neoplasia (or conjunctival-corneal intra-epithelial neoplasia (CCIN)) where topical mitomycin C (MMC) has been used in the treatment regimen. DESIGN Prospective, non-comparative interventional case series. PARTICIPANTS 91 primary or recurrent CCIN lesions from 90 patients treated in a single ocular oncology centre over a 10.5-year period. INTERVENTION 73 cases of localised, non-invasive CCIN and eight cases of recurrent CCIN received a treatment regimen of surgical excision+/-cryotherapy, followed by two to three 1-week cycles of adjuvant topical MMC (0.04% four times a day). 10 cases of diffuse CCIN received two to three 1-week cycles of topical MMC (0.04% four times a day) as sole primary treatment. Main outcome measure Successful treatment was defined as no clinical recurrence of CCIN. RESULTS Mean follow-up of 56.8 months (range 5.8 to 119.8) and median 57.3 months, revealed no recurrences (0%) in the localised primary group, and one persistent case and two recurrences (30%) in the diffuse primary group. There was one recurrence (12.5%) in the recurrent group, but this was in the only eye with a diffuse type of recurrence. CONCLUSIONS MMC treatment following surgical excision appears to decrease the recurrence rate of localised CCIN and should be considered as adjuvant therapy in primary treatment. MMC should also be considered as adjuvant therapy in the treatment of localised recurrent disease. MMC may be used as sole therapy in more diffuse disease, but close ongoing follow-up is recommended in view of the significant risk of persistent or recurrent disease.

  10. Multimodal multispectral imaging of the cervix in vivo for the detection of neoplasia

    NASA Astrophysics Data System (ADS)

    Agrawal, Anant; Harrell, Tim; Bambot, Shabbir B.; Faupel, Mark; Ferris, Daron

    2001-07-01

    Optical spectroscopy has been shown to be an effective method for detecting neoplasia of epithelial tissues. Most studies to date in this realm have applied fluorescence or reflectance spectroscopy alone as a preferred method of disease detection. We have been developing instrumentation which can acquire both reflectance and fluorescence images of the human cervix in vivo, with the goal of combining multispectral information from the two spectroscopic modalities. This instrumentation has been tested on a group of patients in a clinical setting. We have applied spectral and spatial analysis techniques to the acquired images to assess the capabilities of this technology to discriminate neoplastic from normal cervical tissue.

  11. Pregnancy outcomes after chemotherapy for trophoblastic neoplasia.

    PubMed

    Garcia, Mila Trementosa; Lin, Lawrence Hsu; Fushida, Koji; Francisco, Rossana Pulcineli Vieira; Zugaib, Marcelo

    2016-12-01

    The successful development of chemotherapy enabled a fertilitysparing treatment for patients with trophoblastic neoplasia. After disease remission, the outcome of a subsequent pregnancy becomes a great concern for these women. To analyze existing studies in the literature that describe the reproductive outcomes of patients with trophoblastic neoplasia treated with chemotherapy. Systematic review was performed searching for articles on Medline/ Pubmed, Lilacs and Cochrane Library databases, using the terms "gestational trophoblastic disease" and "pregnancy outcome". A total of 18 articles were included. No evidence of decreased fertility after chemotherapy for trophoblastic neoplasia was observed. The abortion rates in patients who conceived within 6 months after chemotherapy was higher compared to those who waited longer. Some studies showed increased rates of stillbirth and repeat hydatidiform moles. Only one work showed increased congenital abnormalities. The pregnancies conceived after chemotherapy for trophoblastic neoplasia should be followed with clinical surveillance due to higher rates of some pregnancy complications. However, studies in the literature provide reassuring data about reproductive outcomes of these patients.

  12. The International Society of Urological Pathology (ISUP) Vancouver Classification of Renal Neoplasia.

    PubMed

    Srigley, John R; Delahunt, Brett; Eble, John N; Egevad, Lars; Epstein, Jonathan I; Grignon, David; Hes, Ondrej; Moch, Holger; Montironi, Rodolfo; Tickoo, Satish K; Zhou, Ming; Argani, Pedram

    2013-10-01

    The classification working group of the International Society of Urological Pathology consensus conference on renal neoplasia was in charge of making recommendations regarding additions and changes to the current World Health Organization Classification of Renal Tumors (2004). Members of the group performed an exhaustive literature review, assessed the results of the preconference survey and participated in the consensus conference discussion and polling activities. On the basis of the above inputs, there was consensus that 5 entities should be recognized as new distinct epithelial tumors within the classification system: tubulocystic renal cell carcinoma (RCC), acquired cystic disease-associated RCC, clear cell (tubulo) papillary RCC, the MiT family translocation RCCs (in particular t(6;11) RCC), and hereditary leiomyomatosis RCC syndrome-associated RCC. In addition, there are 3 rare carcinomas that were considered as emerging or provisional new entities: thyroid-like follicular RCC; succinate dehydrogenase B deficiency-associated RCC; and ALK translocation RCC. Further reports of these entities are required to better understand the nature and behavior of these highly unusual tumors. There were a number of new concepts and suggested modifications to the existing World Health Organization 2004 categories. Within the clear cell RCC group, it was agreed upon that multicystic clear cell RCC is best considered as a neoplasm of low malignant potential. There was agreement that subtyping of papillary RCC is of value and that the oncocytic variant of papillary RCC should not be considered as a distinct entity. The hybrid oncocytic chromophobe tumor, which is an indolent tumor that occurs in 3 settings, namely Birt-Hogg-Dubé Syndrome, renal oncocytosis, and as a sporadic neoplasm, was placed, for the time being, within the chromophobe RCC category. Recent advances related to collecting duct carcinoma, renal medullary carcinoma, and mucinous spindle cell and tubular RCC

  13. The clinical significance of lobular neoplasia on breast core biopsy.

    PubMed

    Karabakhtsian, Rouzan G; Johnson, Ronald; Sumkin, Jules; Dabbs, David J

    2007-05-01

    A core biopsy diagnosis of atypical ductal epithelial hyperplasia is upstaged on follow-up excisional biopsy (FUEB) to in situ or invasive carcinoma in about 20% of cases, thus prompting a FUEB. In contrast, upstaging information for a core biopsy diagnosis of pure lobular neoplasia (LN), without mass lesions or other risk-associated lesions is less clear. In this retrospective study, we report the largest consecutive series of patients who had a breast core biopsy diagnosis of LN and a FUEB. Core needle breast biopsies with a diagnosis of LN were retrieved from our files for the period 1999 to 2005, yielding 110 patients. One hundred and one patients had a follow-up surgical excision. Cases of LN with coexisting high-risk lesions (n=9, 10%) were excluded from the study. Patients with associated mass lesions all had benign findings (n=15, 16%) and had no impact on the study results. The remaining 77 core biopsies had no masses or risk lesions and were mammographically Breast Imaging Reporting and Data System 4 (BIRADS) for microcalcifications. Overall, 8/77 (10%) of patients with a radiographic BIRADS 4 image with calcifications and a core biopsy diagnosis of LN on core biopsy were upstaged on FUEB to ductal carcinoma in situ or invasive carcinoma. The numbers upstaged from core biopsies were as follows: atypical lobular hyperplasia (ALH) 4/52 (8%), mixed ALH/lobular carcinoma in situ (LCIS) 1/9 (10%), and pure LCIS 3/16 (19%). A core biopsy of LCIS with neoplastic epithelial calcifications was nearly 3 times more likely to be upstaged on FUEB compared with ALH. We conclude that a finding of LN on breast core biopsy in a patient with a BIRADS 4 image and calcifications is associated with a risk of 8% to 19% of upstaging to a treatable disease on FUEB.

  14. Coexistence of prostate neoplasia in patients undergoing radical cystoprostatectomy due to vesical neoplasia.

    PubMed

    Romero, Frederico R; de Castro, Marília G; Andriolo Júnior, Adalberto; de Meneses, Alex H; Fernandes, Roni C; Perez, Marjo D C

    2004-01-01

    To assess the incidence of bladder carcinoma infiltrating the prostate and prostate adenocarcinoma in patients undergoing radical cystoprostatectomy due to bladder cancer, as well as to assess if the characteristics of the bladder neoplasia influence the prostatic involvement by this neoplasia. We retrospectively assessed 60 male patients, who underwent radical cystoprostatectomy between July 1997 and December 2003. Mean age was 66.7 years (40 and 93 years). The product of radical cystoprostatectomies was checked for involvement of urethra and prostate parenchyma by the primary neoplasia, and for the presence of associated prostate adenocarcinoma. Bladder neoplasia characteristics, such as localization, size, multifocality, association with in situ carcinoma and histological grade, were studied in order to assess the possibility of using such characteristics as predictive factors of prostate infiltration by bladder urothelial carcinoma. We observed the presence of 20% of patients with bladder carcinoma infiltrating the prostatic urethra, 23.3% of patients with infiltration of the prostate parenchyma and 28.3% of patients with associate prostate adenocarcinoma, resulting in a total of 55% of patients with prostatic involvement (infiltrative bladder carcinoma and/or adenocarcinoma). We also observed a statistically significant correlation between tumor location in the trigone, the presence of in situ carcinoma and the histological grade of the bladder tumor with prostatic infiltration by the vesical neoplasia. The coexistence of prostatic neoplasia in patients operated for bladder neoplasia was frequent in our sample (55%). We observed that the prostatic infiltration by bladder tumors occurs more frequently with tumors located in the trigone, with associated in situ carcinoma and with high histological grade. There was no correlation between neoplastic infiltration of prostate and multifocality or size of the bladder tumor in the studied sample.

  15. The Hirschsprung's-multiple endocrine neoplasia connection.

    PubMed

    Moore, Sam W; Zaahl, Monique

    2012-01-01

    The risk of patients with Hirschsprung's disease later developing multiple endocrine neoplasia remains a matter of concern. The multiple endocrine neoplasia 2-Hirschsprung's disease association has been shown to cosegregate in Hirschsprung's disease patients with both short- and long-segment aganglionosis, although patients with long-segment aganglionosis a to carry the greatest risk. The Hirschsprung's disease-medullary thyroid carcinoma relationship also appears to be bi-directional, and activation or suppression of the rearranged during transfection gene appeared to vary over succeeding generations within the same family. Rearranged during transfection gene variations are associated with both conditions. The cosegregation of Hirschsprung's disease and multiple endocrine neoplasia 2 is particularly interesting as it involves both "switch off" and "switch on" of the rearranged during transfection proto-oncogene in the same patient. This cosegregation mostly relates to the cysteine-rich area on RET620 (the "Janus gene"). The mechanism whereby rearranged during transfection influences gene activation in multiple endocrine neoplasia 2 is complex, but genetic variations impair the rearranged during transfection tyrosine kinase response to tyrosine kinase activation, thus appearing to dictate downstream signaling cascade responses. Better understanding of the RET-620 relationship allows for a more cost-effective method of identifying those at risk by focusing rearranged during transfection gene testing to this specific area as a "hot spot". The clinical awareness of possible medullary thyroid carcinoma has led to timely intervention and early treatment of this chemo- and radioresistant tumor with poor prognosis. Establishment of "risk" by genetic testing has become a classic model of molecular medicine being integrated into patient care and offering rearranged during transfection directed prophylactic surgical management. In addition, novel approaches to treatment

  16. Infection and Cervical Neoplasia: Facts and Fiction

    PubMed Central

    Al-Daraji, Wael I; Smith, John HF

    2009-01-01

    Whilst there is strong evidence that human papillomavirus (HPV) is the principal aetiological agent in cervical neoplasia, some other sexually transmitted agents may either contribute or protect against cervical carcinogenesis, such as the herpes virus family (HSV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), human immunodeficiency virus (HIV) or Chlamydia trachomatis (CT). Epidemiological studies suggest that HSV may have a role in cervical neoplasia, but there is no clear supportive experimental evidence. Serological studies have also failed to reveal a difference in the prevalence of antibodies to CMV and EBV between patients with cervical cancer and controls. However, longitudinal seroepidemiological studies have provided evidence that CT is an independent risk factor for the development of cervical squamous carcinoma and this association is serotype specific. The increased risk of cervical neoplasia in patients infected with HIV has been recognised for over a decade and HIV may interact with HPV either by alternating HPV gene transcription or by immunosuppression. Finally extensive experimental and limited epidemiological evidence suggests that adeno-associated viruses (AAV) may have antioncogenic activity in man and may protect against the development of cervical cancer. At present the mechanism of this action is unclear but may relate to AAV-induced regulation of HPV gene expression and the HPV life cycle. In this review we summarize the current literature relating to the associations and mechanisms of cervical carcinogenesis by each of these infectious microorganisms. PMID:18830380

  17. [International Society of Urological Pathology (ISUP) Vancouver Classification of Renal Neoplasia 2012].

    PubMed

    Hes, Ondřej

    2014-01-01

    Kidney tumours form a broad spectrum of distinguished histopathological and molecular genetic entities. The last WHO classification is dated to 2004. Current classification has been published in October 2013 by ISUP (International Society of Urological Pathology). There were 5 new epithelials tumours: tubulocystic renal cell carcinoma (RCC), acquired cystic disease-associated RCC, clear cell (tubulo-)papillary RCC, the MiT family translocation RCCs (in particular t(6;11) RCC), and hereditary leiomyomatosis RCC syndrome-associated RCC. Another 3 subtypes of RCC were added as "provisional" entities: thyroid-like follicular RCC; succinate dehydrogenase B deficiency-associated RCC; and ALK translocation RCC. Modifications were performed in already existing entities: multicystic clear cell RCC (formerly multilocular cystic RCC) is newly included as a subcategory of clear cell RCC with low malignant potential. Oncocytic papillary RCC (PRCC) has not been recognized as a distinctive subcategory of PRCC yet. Hybrid oncocytic-chromophobe tumour was placed within the chromophobe RCC category. Recent advances related to collecting duct carcinoma, renal medullary carcinoma, and mucinous spindle cell and tubular RCC were elucidated. Outside of the epithelial category, current approach to our understanding of angiomyolipoma, including the epithelioid variant and angiomyolipoma with epithelial cysts was clarified. Cystic nephroma and mixed epithelial and stromal tumour were considered as a spectrum of one entity. Synovial sarcoma was placed within the sarcoma group. The new classification is to be referred to as the International Society of Urological Pathology Vancouver Classification of Renal Neoplasia.

  18. 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

  19. Dicer Is Required for Maintenance of Adult Pancreatic Acinar Cell Identity and Plays a Role in Kras-Driven Pancreatic Neoplasia

    PubMed Central

    Wang, Yue J.; McAllister, Florencia; Bailey, Jennifer M.; Scott, Sherri-Gae; Hendley, Audrey M.; Leach, Steven D.; Ghosh, Bidyut

    2014-01-01

    The role of miRNA processing in the maintenance of adult pancreatic acinar cell identity and during the initiation and progression of pancreatic neoplasia has not been studied in detail. In this work, we deleted Dicer specifically in adult pancreatic acinar cells, with or without simultaneous activation of oncogenic Kras. We found that Dicer is essential for the maintenance of acinar cell identity. Acinar cells lacking Dicer showed increased plasticity, as evidenced by loss of polarity, initiation of epithelial-to-mesenchymal transition (EMT) and acinar-to-ductal metaplasia (ADM). In the context of oncogenic Kras activation, the initiation of ADM and pancreatic intraepithelial neoplasia (PanIN) were both highly sensitive to Dicer gene dosage. Homozygous Dicer deletion accelerated the formation of ADM but not PanIN. In contrast, heterozygous Dicer deletion accelerated PanIN initiation, revealing complex roles for Dicer in the regulation of both normal and neoplastic pancreatic epithelial identity. PMID:25405615

  20. Pediatric implications of multiple endocrine neoplasia.

    PubMed

    Girvan, D P; Holliday, R L

    1987-09-01

    The association of endocrine tumors from several sites has been known for over 50 years but the familial aspects of these relationships have only been appreciated since 1954. The original term multiple familial endocrine adenomatosis (MEA) was changed to multiple endocrine neoplasia (MEN). This report describes two children aged 8 and 11 years, who are cousins with MEN IIa. A strong family history prompted investigation of these children. Pentagastrin stimulation resulted in elevated serum calcitonin levels and subsequent surgery. Unsuspected medullary thyroid carcinoma was found in each child. Proper screening of high-risk individuals should prevent this potentially lethal condition from becoming a major problem.

  1. 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

  2. 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.

  3. Thyroid neoplasia in captive raccoons (Procyon lotor).

    PubMed

    McCain, Stephanie L; Allender, Matthew C; Bohling, Mark; Ramsay, Edward C; Morandi, Federica; Newkirk, Kimberly M

    2010-03-01

    Two adult, spayed, female raccoons were diagnosed with thyroid neoplasia. One raccoon had a palpable, left-sided, nonfunctional thyroid adenocarcinoma which was treated with a thyroidectomy twice with local recurrence both times. After the second recurrence, pulmonary metastases were identified. A third thyroidectomy was performed, and a vascular access port was placed for administration of intravenous doxorubicin. The raccoon developed pancytopenia and became anorexic after chemotherapy, and the owner elected humane euthanasia. The second raccoon had nonpalpable, bilateral, functional follicular thyroid adenomatous hyperplasia and was treated with a right thyroidectomy and a partial left thyroidectomy, leaving behind the grossly normal portion of the left thyroid. However, the animal was still hyperthyroid after surgery and was then successfully managed with topical methimazole gel. Thyroid pathology has been documented in raccoons in Europe, but is not reported in the United States. Thyroid neoplasia in raccoons can occur as a nonfunctional adenocarcinoma, as is commonly reported in dogs, or as a functional adenoma, as is commonly reported in cats. Raccoons with adenocarcinomas should be evaluated for pulmonary metastasis. Methimazole gel may be a viable treatment option for raccoons with hyperthyroidism.

  4. Psychosocial stress and cervical neoplasia risk.

    PubMed

    Coker, Ann L; Bond, Sharon; Madeleine, Margaret M; Luchok, Kathryn; Pirisi, Lucia

    2003-01-01

    We assessed the association between psychosocial stress and preinvasive cervical neoplasia development controlling for HR-HPV infection. This case-control study enrolled low-income women receiving family planning services at health department clinics. There were 59 cases with biopsy confirmed HSIL and 163 with low-grade SIL and 160 controls with normal cervical cytology. A modified SLE scale was used to measure stressful events and the perceived impact of the event in the prior 5 years. Unconditional logistic regression was used to assess SIL risk and stressful events scores and by subscales. After adjusting for age, HR-HPV infection, and lifetime number of sex partners, the SLE count score was associated with an increased risk of SIL among white women (aOR = 1.20; 95% CI = 1.04, 1.38) yet not among African American women (aOR = 1.02; 95% CI = 0.87, 1.19). The relationship stress subscale (divorce, infidelity, an increase in the number of arguments, and psychological and physical partner violence) was the only one of four subscales (loss, violence, and financial stress) associated with SIL, again, only among white women (aOR = 1.54; 95% CI = 1.21, 1.96). These data suggest that psychosocial stress may play a role in SIL development. Future studies are needed to confirm these findings, to explore racial difference in reporting stress, and to explore the mechanism through which psychosocial stress may affect cervical neoplasia risk.

  5. Biliary Intraepithelial Neoplasia (BilIN) in Primary Sclerosing Cholangitis: The First Report from Iran

    PubMed Central

    Akbarzadeh, Laleh; Geramizadeh, Bita; Kazemi, Kurosh; Nikeghbalian, Saman; Malekhosseini, Seyedali

    2016-01-01

    Background Primary sclerosing cholangitis (PSC) as one of the most common chronic cholestatic liver diseases is a main predisposing factor for the development of cholangiocarcinoma (CCA). Biliary intraepithelial neoplasia (BilIN) is defined as precancerous bile duct epithelial changes, which can be eventually led to cholangiocarcinoma. There are very few studies about the frequency of BilIN in the patients with PSC and its correlation with paraclinical findings. Objectives In this study, we tried to find the frequency of BilIN in the patients with PSC and correlate its presence with clinicopathologic factors. Methods During two years (2014 - 15) of investigation, 80 explanted livers with the confirmed diagnosis of PSC were studied through precise inspection and thorough sectioning of the explanted livers. These findings were correlated with paraclinical findings to identify any predictor of these neoplastic epithelial changes. Results During the study period of 2 years, among 80 livers with confirmed diagnosis of PSC, there were 43 cases with different types of metaplasia. The frequency of epithelial changes was as below: 29 (35%) for pyloric metaplasia, 9 (10.8%) for mucinous metaplasia, 3 (3.6%) for intestinal metaplasia, 1 (1.2%) for osteoid metaplasia, and 1 (1.2%) for squamous metaplasia. There was no epithelial dysplasia in the study sample; however, according to the most recent reports, mucinous metaplasia is considered as BilIN 1; therefore, there would be 9 cases of BilIN I. There has been no statistically significant difference between PSC cases and those with BilIN in demographic variables, except for bilirubin and CA19-9 which were higher in the PSC cases with BilIN. Conclusions This study showed that the frequency of BilIN was low among Iranian patients with PSC. High bilirubin and CA19-9 can be predictors of the development of bile duct epithelial changes in patients with PSC. PMID:28123440

  6. Angiotensin-(1-7)/Mas Signaling Inhibits Lipopolysaccharide-Induced ADAM17 Shedding Activity and Apoptosis in Alveolar Epithelial Cells.

    PubMed

    Ma, Xinhua; Xu, Daomiao; Ai, Yuhang; Zhao, Shuangping; Zhang, Lina; Ming, Guangfeng; Liu, Zhiyong

    2016-01-01

    A disintegrin and metalloproteinase (ADAM) 17, constitutively expressed in alveolar epithelium, is the pivotal shedding enzyme mediating acute lung inflammation. On the other hand, angiotensin (Ang)-(1-7)/Mas signaling has been shown to improve acute respiratory distress syndrome and protect alveolar epithelial cells from apoptosis. In this study, we explored the effect of Ang-(1-7)/Mas signaling on the expression and activity of ADAM17 and assessed its impact on apoptosis in lipopolysaccharide (LPS)-treated human alveolar epithelial cells. LPS markedly induced the shedding activity of ADAM17 in alveolar epithelial cells, which was blocked by selective c-Jun N-terminal kinase (JNK) inhibitor SP600125. Ang-(1-7) concentration-dependently inhibited LPS-induced ADAM17 shedding activity, which was abolished by selective Mas blocker A779 and Mas shRNA. LPS and Ang-(1-7) showed no significant effect on the expression of ADAM17. Overexpression of ADAM17 synergized with LPS on increasing the shedding activity of ADAM17 and apoptosis in alveolar epithelial cells, counteracting the inhibitory effects of Ang-(1-7). In addition, LPS significantly increased the JNK activity in alveolar epithelial cells; Ang-(1-7) concentration-dependently inhibited LPS-induced JNK activity, which was abolished by A779 and Mas shRNA. In conclusion, this study suggests that Ang-(1-7)/Mas signaling inhibits LPS-induced alveolar epithelial cell apoptosis by inhibiting LPS-induced shedding activity of ADAM17, likely by a JNK-dependent mechanism. © 2015 S. Karger AG, Basel.

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

    PubMed

    de Carvalho, Danielle Lima Corrêa; do Canto, Alan Motta; Eduardo, Fernanda de Paula; Bezinelli, Letícia Mello; Costa, André Luiz Ferreira; Braz-Silva, Paulo Henrique

    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.

  8. 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

  9. Applications and Advancements in the use of High-Resolution Microendoscopy for Detection of Gastrointestinal Neoplasia

    PubMed Central

    Louie, Justin S.; Richards-Kortum, Rebecca; Anandasabapathy, Sharmila

    2014-01-01

    The high-resolution microendoscope (HRME) is a novel imaging modality that allows real-time epithelial imaging at subcellular resolution. Used in concert with any standard endoscope, this portable, low cost, ‘optical biopsy’ technology has the ability to provide images of cellular morphology during a procedure. This technology has been the subject of a number of studies investigating its use in screening and surveillance of a range of gastrointestinal neoplasia, including esophageal adenocarcinoma(EAC), esophageal squamous cell cancer(ESCC), colorectal neoplasia(CRC) and anal neoplasia. These studies have shown that HRME is a modality that consistently provides high specificity, negative predictive value, and accuracy across different diseases. In addition, they have illustrated that HRME users can be relatively easily trained in a short period of time and that users have demonstrated solid inter-rater reliability. These features make HRME a potential complement to high definition white light imaging, narrow band imaging and other ‘red flag technologies’ in facilitating real-time clinical diagnosis, endoscopic therapy and margin determination. Further clinical validation is needed to determine whether this translates to reduced procedure times, pathology costs, and follow up procedures. Finally, the HRME has a relatively simple design compared to other similar technologies, making it portable, simple to maintain, and low cost. This may allow the HRME device to function in both advanced care settings as well as in places with less resources and specialized support systems. As a whole, the HRME device has shown good performance along with low-cost and portable construction, and its application in different conditions and settings has been promising. PMID:25108219

  10. Applications and advancements in the use of high-resolution microendoscopy for detection of gastrointestinal neoplasia.

    PubMed

    Louie, Justin S; Richards-Kortum, Rebecca; Anandasabapathy, Sharmila

    2014-11-01

    The high-resolution microendoscope (HRME) is a novel imaging modality that allows real-time epithelial imaging at subcellular resolution. Used in concert with any standard endoscope, this portable, low cost, "optical biopsy" technology has the ability to provide images of cellular morphology during a procedure. This technology has been the subject of a number of studies investigating its use in screening and surveillance of a range of gastrointestinal neoplasias, including esophageal adenocarcinoma, esophageal squamous cell cancer, colorectal neoplasia, and anal neoplasia. These studies have shown that HRME is a modality that consistently provides high specificity, negative predictive value, and accuracy across different diseases. In addition, they have illustrated that HRME users can be relatively easily trained in a short period of time, and that users have demonstrated solid inter-rater reliability. These features make HRME a potential complement to high-definition white-light imaging, narrow-band imaging, and other red flag technologies in facilitating real-time clinical diagnosis, endoscopic therapy, and margin determination. Further clinical validation is needed to determine whether this translates to reduced procedure times, pathology costs, and follow-up procedures. Finally, the HRME has a relatively simple design compared with other similar technologies, making it portable, simple to maintain, and low cost. This may allow the HRME device to function in both advanced care settings as well as in places with less resources and specialized support systems. As a whole, the HRME device has shown good performance along with low cost and portable construction, and its application in different conditions and settings has been promising. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

  11. Epithelial BMP signaling is required for proper specification of epithelial cell lineages and gastric endocrine cells

    PubMed Central

    Maloum, Faïza; Allaire, Joannie M.; Gagné-Sansfaçon, Jessica; Roy, Evelyne; Belleville, Karine; Sarret, Philippe; Morisset, Jean; Carrier, Julie C.; Mishina, Yuji; Kaestner, Klaus H.

    2011-01-01

    Bone morphogenetic protein (BMP) signaling within the gastrointestinal tract is complex. BMP ligands and their receptors are expressed in both epithelial and mesenchymal compartments, suggesting bidirectional signaling between these two entities. Despite an increasing interest in BMP signaling in gut physiology and pathologies, the distinct contribution of BMP signaling in the epithelium vs. the mesenchyme in gastrointestinal homeostasis remains to be established. We aimed to investigate the role of epithelial BMP signaling in gastric organogenesis, gland morphogenesis, and maintenance of epithelial cell functions. Using the Cre/loxP system, we generated a mouse model with an early deletion during development of BMP receptor 1A (Bmpr1a) exclusively in the foregut endoderm. Bmpr1aΔGEC mice showed no severe abnormalities in gastric organogenesis, gland epithelial proliferation, or morphogenesis, suggesting only a minor role for epithelial BMP signaling in these processes. However, early loss of BMP signaling in foregut endoderm did impact on gastric patterning, leading to an anteriorization of the stomach. In addition, numbers of parietal cells were reduced in Bmpr1aΔGEC mice. Epithelial BMP deletion significantly increased the numbers of chromogranin A-, ghrelin-, somatostatin-, gastrin-, and serotonin-expressing gastric endocrine cells. Cancer never developed in young adult (<100 days) Bmpr1a-inactivated mice although a marker of spasmolytic polypeptide-expressing metaplasia was upregulated. Using this model, we have uncovered that BMP signaling negatively regulates the proliferation and commitment of endocrine precursor cells. Our data also indicate that loss of BMP signaling in epithelial gastric cells alone is not sufficient to induce gastric neoplasia. PMID:21415412

  12. Isoprenylcysteine carboxylmethyltransferase deficiency exacerbates KRAS-driven pancreatic neoplasia via Notch suppression

    PubMed Central

    Court, Helen; Amoyel, Marc; Hackman, Michael; Lee, Kyoung Eun; Xu, Ruliang; Miller, George; Bar-Sagi, Dafna; Bach, Erika A.; Bergö, Martin O.; Philips, Mark R.

    2013-01-01

    RAS is the most frequently mutated oncogene in human cancers. Despite decades of effort, anti-RAS therapies have remained elusive. Isoprenylcysteine carboxylmethyltransferase (ICMT) methylates RAS and other CaaX-containing proteins, but its potential as a target for cancer therapy has not been fully evaluated. We crossed a Pdx1-Cre;LSL-KrasG12D mouse, which is a model of pancreatic ductal adenocarcinoma (PDA), with a mouse harboring a floxed allele of Icmt. Surprisingly, we found that ICMT deficiency dramatically accelerated the development and progression of neoplasia. ICMT-deficient pancreatic ductal epithelial cells had a slight growth advantage and were resistant to premature senescence by a mechanism that involved suppression of cyclin-dependent kinase inhibitor 2A (p16INK4A) expression. ICMT deficiency precisely phenocopied Notch1 deficiency in the Pdx1-Cre;LSL-KrasG12D model by exacerbating pancreatic intraepithelial neoplasias, promoting facial papillomas, and derepressing Wnt signaling. Silencing ICMT in human osteosarcoma cells decreased Notch1 signaling in response to stimulation with cell-surface ligands. Additionally, targeted silencing of Ste14, the Drosophila homolog of Icmt, resulted in defects in wing development, consistent with Notch loss of function. Our data suggest that ICMT behaves like a tumor suppressor in PDA because it is required for Notch1 signaling. PMID:24216479

  13. Multiphoton imaging of low grade, high grade intraepithelial neoplasia and intramucosal invasive cancer of esophagus

    NASA Astrophysics Data System (ADS)

    Xu, Jian; Jiang, Liwei; Kang, Deyong; Wu, Xuejing; Xu, Meifang; Zhuo, Shuangmu; Zhu, Xiaoqin; Lin, Jiangbo; Chen, Jianxin

    2017-04-01

    Esophageal squamous cell carcinoma (ESCC) is devastating because of its aggressive lymphatic spread and clinical course. It is believed to occur through low-grade intraepithelial neoplasia (LGIN), high-grade intraepithelial neoplasia (HGIN), and intramucosal invasive cancer (IMC) before transforming to submucosal cancer. In particular, these early lesions (LGIN, HGIN and IMC), which involve no lymph node nor distant metastasis, can be cured by endoscopic treatment. Therefore, early identification of these lesions is important so as to offer a curative endoscopic resection, thus slowing down the development of ESCC. In this work, spectral information and morphological features of the normal esophageal mucosa are first studied. Then, the morphological changes of LGIN, HGIN and IMC are described. Lastly, quantitative parameters are also extracted by calculating the nuclear-to-cytoplasmic ratio of epithelial cells and the pixel density of collagen in the lamina propria. These results show that multiphoton microscopy (MPM) has the ability to identify normal esophageal mucosa, LGIN, HGIN and IMC. With the development of multiphoton endoscope systems for in vivo imaging, combined with a laser ablation system, MPM has the potential to provide immediate pathologic diagnosis and curative treatment of ESCC before the transformation to submucosal cancer in the future.

  14. Notch2 is required for progression of pancreatic intraepithelial neoplasia and development of pancreatic ductal adenocarcinoma.

    PubMed

    Mazur, Pawel K; Einwächter, Henrik; Lee, Marcel; Sipos, Bence; Nakhai, Hassan; Rad, Roland; Zimber-Strobl, Ursula; Strobl, Lothar J; Radtke, Freddy; Klöppel, Günter; Schmid, Roland M; Siveke, Jens T

    2010-07-27

    Pancreatic cancer is one of the most fatal malignancies lacking effective therapies. Notch signaling is a key regulator of cell fate specification and pancreatic cancer development; however, the role of individual Notch receptors and downstream signaling is largely unknown. Here, we show that Notch2 is predominantly expressed in ductal cells and pancreatic intraepithelial neoplasia (PanIN) lesions. Using genetically engineered mice, we demonstrate the effect of conditional Notch receptor ablation in KrasG12D-driven pancreatic carcinogenesis. Deficiency of Notch2 but not Notch1 stops PanIN progression, prolongs survival, and leads to a phenotypical switch toward anaplastic pancreatic cancer with epithelial-mesenchymal transition. By expression profiling, we identified increased Myc signaling regulated by Notch2 during tumor development, placing Notch2 as a central regulator of PanIN progression and malignant transformation. Our study supports the concept of distinctive roles of individual Notch receptors in cancer development.

  15. 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

  16. Ablation of neoplasia by direct current.

    PubMed

    Taylor, T V; Engler, P; Pullan, B R; Holt, S

    1994-08-01

    The application of low-voltage direct electrical current (DEC) has been studied in animals and humans for the ablation of anal condylomata, oesophageal cancer and Kaposi's sarcoma. Twenty milliamps of DEC passed through multiple 6 cm x 1 cm, flat-plate longitudinal electrodes into the squamous mucosa of the oesophagus of healthy dogs for periods ranging from 10 min to 2 h resulted in denudation and necrosis of the oesophageal mucosa at the site of application of the current. In humans, the application of DEC to two patients with benign anal condyloma acuminata, three patients with inoperable obstructing oesophageal cancer and one patient with disseminated Kaposi sarcoma resulted in striking necrosis of tumour tissue that was confirmed by macroscopic and microscopic studies. These initial findings imply promising therapeutic potential for the use of DEC as a simple, effective, safe, low-cost alternative for ablation of neoplasia.

  17. 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.

  18. Neoplasia in fast neutron-irradiated beagles

    SciTech Connect

    Bradley, E.W.; Zook; B.C.; Casarett, G.W.

    1981-09-01

    One hundred fifty-one beagle dogs were irradiated with either photons or fast neutrons (15 MeV) to one of three dose-limiting normal tissues - spinal cord, lung, or brain. The radiation was given in four fractions per week for 5 weeks (spinal cord), 6 weeks (lung), 7 weeks (brain) to total doses encompassing those given clinically for cancer management. To date, no nonirradiated dogs or photon-irradiated dogs have developed neoplasms within the irradiated field. Of the neutron-irradiated dogs at risk, the incidence of neoplasia was 15%. The latent period for radiation-induced cancers has varied from 1 to 4 1/2 years at this time in the study.

  19. Carbon dioxide laser management cervical intraepithelial neoplasia

    SciTech Connect

    Bellina, J.H.; Wright, V.C.; Voros, J.I.; Riopelle, M.A.; Hohenschutz, V.

    1981-12-01

    In this report we describe the use of the carbon dioxide laser for the outpatient management of cervical intraepithelial neoplasia (CIN). A comparison of treatment effectiveness for different grades of CIN is also included. Two hundred fifty-six cases were evaluated by colposcopy, cytology, and histopathology, treated by at least 5 to 6 mm of laser vaporization, and followed up for an average of 10.7 months. Follow-up examinations included cytology, colposcopy, and directed biopsy if a suspicious lesion was discovered. During the follow-up, 18 cases of persistent CIN were identified (7.0%). Most of these were successfully managed with repeat laser treatment. Overall success of laser surgery for CIN, one or two applications, was 97.6%. Few complications were encountered. Laser surgery appears to offer acceptable treatment effectiveness, early identification of persistent disease, and easy retreatment when required. (Am. J. Obstet. Gynecol. 141:828, 1981.)

  20. Neoplasia in fast neutron-irradiated beagles

    SciTech Connect

    Bradley, E.W.; Zook, B.C.; Casarett, G.W.; Deye, J.A.; Adoff, L.M.; Rogers, C.C.

    1981-09-01

    One hundred fifty-one beagle dogs were irradiated with either photons or fast neutrons (15 MeV) to one of three dose-limiting normal tissues--spinal cord, lung, or brain. The radiation was given in four fractions per week for 5 weeks (spinal cord), 6 weeks (lung), or 7 weeks (brain) to total doses encompassing those given clinically for cancer management. To date, no nonirradiated dogs or photon-irradiated dogs have developed any neoplasms. Seven dogs receiving fast neutrons have developed 9 neoplasms within the irradiated field. Of the neutron-irradiated dogs at risk, the incidence of neoplasia was 15%. The latent period for radiation-induced cancers has varied from 1 to 4 1/2 years at this time in the study.

  1. A Case of Solitary Nonvascularized Corneal Epithelial Dysplasia.

    PubMed

    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.

  2. Apoptotic index for prediction of postmolar gestational trophoblastic neoplasia.

    PubMed

    Braga, Antonio; Maestá, Izildinha; Rocha Soares, Renan; Elias, Kevin M; Custódio Domingues, Maria Aparecida; Barbisan, Luis Fernando; Berkowitz, Ross S

    2016-09-01

    Although 85% of patients with a complete hydatidiform mole achieve spontaneous remission after a few months, 15% of them will experience gestational trophoblastic neoplasia, which requires chemotherapy. To date, there is no biomarker to predict post-molar gestational trophoblastic neoplasia before the initiation of human chorionic gonadotropin surveillance. The purpose of this study was to assess the relationship between the expression of apoptosis markers in the molar villous trophoblasts and the subsequent development of gestational trophoblastic neoplasia after the evacuation of a complete hydatidiform mole. This was a retrospective cohort study of patients with complete hydatidiform mole who were diagnosed, treated, and followed at the Center of Trophoblastic Diseases (Botucatu/São Paulo State and Rio de Janeiro/Rio de Janeiro State, Brazil) from 1995-2014. Patients were divided temporally into derivation (1995-2004) and validation (2005-2014) cohorts. Immunohistochemistry was used to examine tissue expression of the apoptosis inhibitor survivin or the pro-apoptotic enzyme caspase-3. Survivin stains for cytoplasmic and nuclear expression were evaluated independently. Caspase-3 expression was measured as an apoptotic index of positive staining cells over negative staining cells multiplied by 100. Receiver operating characteristic curves were then constructed, and the area under the curve was calculated to test the performance characteristics of the staining to predict the subsequent development of gestational trophoblastic neoplasia. The final study population comprised 780 patients, with 390 patients in each temporal cohort: 590 patients entered spontaneous remission, and 190 patients experienced post-molar gestational trophoblastic neoplasia. Neither nuclear nor cytoplasmic survivin expression performed well as a predictor of subsequent gestational trophoblastic neoplasia. The caspase-3 apoptotic index was a strong risk factor for subsequent gestational

  3. Remodeling of the epithelial-connective tissue interface (ECTI) in oral epithelial dysplasia as visualized by noninvasive 3D imaging

    PubMed Central

    Pal, Rahul; Shilagard, Tuya; Yang, Jinping; Villarreal, Paula; Brown, Tyra; Qiu, Suimin; McCammon, Susan; Resto, Vicente; Vargas, Gracie

    2016-01-01

    Early neoplastic features in oral epithelial dysplasia are first evident at the basal epithelium positioned at the epithelial-connective tissue interface (ECTI), separating the basal epithelium from the underlying lamina propria. The ECTI undergoes significant deformation in early neoplasia due to focal epithelial expansion and proteolytic remodeling of the lamina propria but few studies have examined these changes. In the present study, we quantitated alterations in ECTI topography in dysplasia using in vivo volumetric multiphoton autofluorescence microscopy and second harmonic generation microscopy. The label-free method allows direct noninvasive visualization of the ECTI surface without perturbing the epithelium. An image-based parameter, ‘ECTI contour’, is described that indicates deformation of the ECTI surface. ECTI contour was higher in dysplasia than control or inflammed specimens, indicating transition from flat to a deformed surface. Cellular parameters of nuclear area, nuclear density, coefficient of variation in nuclear area in the basal epithelium and collagen density in areas adjacent to ECTI were measured. ECTI contour differentiated dysplasia from control/benign mucosa with higher sensitivity and specificity than basal nuclear density or basal nuclear area, comparable to coefficient of variation in nuclear area and collagen density. The presented method offers a unique opportunity to study ECTI in intact mucosa with simultaneous assessment of cellular and extracellular matrix features, expanding opportunities for studies of early neoplastic events near this critical interface and potentially leading to development of new approaches for detecting neoplasia in vivo. PMID:27302162

  4. Tumor suppressor roles of CENP-E and Nsl1 in Drosophila epithelial tissues.

    PubMed

    Clemente-Ruiz, Marta; Muzzopappa, Mariana; Milán, Marco

    2014-01-01

    Depletion of spindle assembly checkpoint (SAC) genes in Drosophila epithelial tissues leads to JNK-dependent programmed cell death and additional blockade of the apoptotic program drives tumorigenesis. A recent report proposes that chromosomal instability (CIN) is not the driving force in the tumorigenic response of the SAC-deficient tissue, and that checkpoint proteins exert a SAC-independent tumor suppressor role. This notion is based on observations that the depletion of CENP-E levels or prevention of Bub3 from binding to the kinetochore in Drosophila tissues unable to activate the apoptotic program induces CIN but does not cause hyperproliferation. Here we re-examined this proposal. In contrast to the previous report, we observed that depletion of CENP-E or Nsl1-the latter mediating kinetochore targeting of Bub3-in epithelial tissues unable to activate the apoptotic program induces significant levels of aneuploidy and drives tumor-like growth. The induction of the JNK transcriptional targets Wingless, a mitogenic molecule, and MMP1, a matrix metaloproteinase 1 involved in basement membrane degradation was also observed in these tumors. An identical response of the tissue was previously detected upon depletion of several SAC genes or genes involved in spindle assembly, chromatin condensation, and cytokinesis, all of which have been described to cause CIN. All together, these results reinforce the role of CIN in driving tumorigenesis in Drosophila epithelial tissues and question the proposed SAC-independent roles of checkpoint proteins in suppressing tumorigenesis. Differences in aneuploidy rates might explain the discrepancy between the previous report and our results.

  5. Genetics of Multiple Endocrine Neoplasia Type 1/Multiple Endocrine Neoplasia Type 2 Syndromes.

    PubMed

    Hyde, Samuel M; Cote, Gilbert J; Grubbs, Elizabeth G

    2017-06-01

    Multiple endocrine neoplasia syndromes types 1 and 2 represent well-characterized yet clinically heterogeneous hereditary conditions for which diagnostic and management recommendations exist; genetic testing for these inherited endocrinopathies is included in these guidelines and is an important part of identifying affected patients and their family members. Understanding of these mature syndromes is challenged as more individuals undergo genetic testing and genetic data are amassed, with the potential to create clinical conundrums that may have an impact on individualized approaches to management and counseling. Clinicians who diagnose and treat patients with MEN syndromes should be aware of these possibilities. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. 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

  7. Synchronous fluorescence spectroscopy of colon neoplasia

    NASA Astrophysics Data System (ADS)

    Borisova, Ekaterina; Semyachkina-Glushkovskaya, Oxana; Genova, Tsanislava; Penkov, Nikolay; Terziev, Ivan; Vladimirov, Borislav; Avramov, Latchezar

    2017-03-01

    Synchronous fluorescence spectroscopy (SFS) is a steady-state approach that we used for evaluation of specific fluorescence characteristics of cancerous colorectal tissues. SFS allow narrowing of the fluorescence spectra received, which increase the spectral resolution and improve the analysis of the fluorescence origin in such complex objects, such as biological tissues. In our study we investigate the characteristic differences, with diagnostic meaning, in the synchronous fluorescence spectra (SFS) of cancerous and healthy colorectal tissues ex vivo using a spectrofluorimeter FluoroLog3 (HORIBA, JobinYvon, France) for obtaining of the SFS data in a broad spectral range (300-800 nm) using excitation in the range of 280-440 nm with a delta lambda between 0 and 200 nm with a 10 nm step between scanning excitation and emission data. The procedure of obtaining the investigated samples ex vivo includes their excision during surgery for removal of neoplasia lesions. After the surgical removal biological samples are transported in isothermal conditions and safekeeping solution from the hospital to the spectral laboratory, where their spectral properties were investigated. All patients received and signed written informed consent and this research is approved by Ethics committee of University Hospital "Tsaritsa Yoanna", Sofia. Histological analysis was used as "gold standard" for evaluation of tissue samples and comparison of the spectral data received.

  8. Pheochromocytomas in Multiple Endocrine Neoplasia Type 2.

    PubMed

    Tsang, Venessa H M; Tacon, Lyndal J; Learoyd, Diana L; Robinson, Bruce G

    2015-01-01

    Pheochromocytoma (PC) is a neuroendocrine tumor that originates from chromaffin cells of the adrenal medulla. The production of catecholamines, including epinephrine, norepinephrine and dopamine, may lead to haemodynamic instability. Over 30% of PCs are associated with germline mutations, including re-arranged in transfection (RET) mutations seen in multiple endocrine neoplasia type 2 (MEN2) syndromes. Around 40% of individuals with MEN2 develop PC, though it is rarely the presenting feature. Compared to sporadic PC, MEN2-associated PC is more likely to be epinephine secreting and demonstrate bilateral adrenal involvement, and is less likely to be malignant. The diagnosis of PC requires clinical suspicion and biochemical testing, followed by imaging studies. Novel nuclear medicine modalities, including FDG positron emission tomography (PET) and 68Ga DOTATATE PET have added to the conventional techniques of 123I-metaiodobenzylguanindine (MIBG) scintigraphy, computer tomography and magnetic resonance imaging. Treatment of PC is surgical and requires peri-operative alpha and, frequently, beta blockade. Novel surgical techniques, such as adrenal sparing surgery and a laparoscopic approach, have decreased peri-operative morbidity. Surveillance for PC is life long, due to the risk of metastatic disease.

  9. Histologic classification of penile intraepithelial neoplasia.

    PubMed

    Velazquez, Elsa F; Chaux, Alcides; Cubilla, Antonio L

    2012-05-01

    Penile squamous cell carcinomas (SCCs) and their corresponding precancerous lesions can be classified in 2 major groups: human papillomavirus (HPV) related and HPV unrelated. In the former (warty and basaloid SCC), there is a predominance of undifferentiated basaloid cells. In the latter (eg, usual, papillary, and verrucous SCC), the predominant cell is larger with abundant eosinophilic cytoplasm. Based on these morphologic features, a new term, "penile intraepithelial neoplasia" (PeIN), was proposed. PeIN was further subclassified into differentiated and undifferentiated, with the latter being subdivided into basaloid, warty, and warty-basaloid subtypes. Macroscopically, PeIN subtypes are indistinguishable. Microscopically, differentiated PeIN is characterized by acanthosis, parakeratosis, enlarged keratinocytes with abundant "pink" cytoplasm (abnormal maturation), and hyperchromatic cells in the basal layer. In basaloid PeIN the epithelium is replaced by a monotonous population of uniform, small, round, and basophilic cells. Warty PeIN is characterized by a spiky surface, prominent atypical parakeratosis, and pleomorphic koilocytosis. Warty-basaloid PeIN show features of both warty and basaloid PeIN. There is a significant association of subtypes of PeIN with specific variants of invasive SCCs. This is a simple and reproducible nomenclature for penile precancerous lesions based on cell type and differentiation. It takes into account the similarities between vulvar and penile pathology and the hypothesis of a bimodal pathway of penile cancer progression.

  10. 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.

  11. Frequent TERT Promoter Mutations in Ocular Surface Squamous Neoplasia.

    PubMed

    Scholz, Simone L; Thomasen, Henning; Reis, Henning; Möller, Inga; Darawsha, Raid; Müller, Bettina; Dekowski, Dirk; Sucker, Antje; Schilling, Bastian; Schadendorf, Dirk; Steuhl, Klaus-Peter; Paschen, Annette; Westekemper, Henrike; Meller, Daniel; Griewank, Klaus G

    2015-09-01

    Ocular surface squamous neoplasia, including intraepithelial neoplasia (CIN) and invasive squamous cell carcinoma (SCC), are one of the most common malignant tumors of the conjunctiva. Little is known of the genetic alterations involved in their pathogenesis. Promoter mutations in telomerase reverse transcriptase (TERT) have been identified in various cancers, including many associated with ultraviolet (UV) exposure. Our study analyzes the mutation rate and clinicopathological associations of TERT promoter mutations in ocular surface squamous neoplasia. DNA was isolated and the region of the TERT promoter where hotspot mutations can occur analyzed by Sanger-sequencing in 48 ocular surface squamous neoplasia tumor samples (6 CIN and 42 SCC). An analysis of associations between TERT promoter mutation status and various clinicopathological parameters was performed. We identified TERT promoter mutations in 21 of 48 ocular surface squamous neoplasia samples (43.8%), including 4 in CIN and 17 in SCC. The mutations consisted of 8 Chr.5:1295228C>T, 1 Chr.5:1295228_1295229CC>TT, 5 Chr.5:1295242_1295243CC>TT, and 12 Chr.5:1295250C>T mutations. All mutations were C>T or CC>TT alterations, demonstrating a UV-signature. TERT promoter mutations showed no statistically significant associations with clinicopathological parameters. Telomerase reverse transcriptase promoter mutations are found in almost half of ocular surface squamous neoplasias and have a mutation profile supporting UV induction as the major source of mutagenesis. We conclude that UV induced TERT promoter mutations leading to aberrant overexpression of telomerase is a major pathogenetic factor in ocular surface squamous neoplasia.

  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. [Prophylactic thyroidectomy in multiple endocrine neoplasia syndrome].

    PubMed

    Marijuán, V; León, S; Moreno, F; Carles, C; Roca, A; García-Sala, C; Ponce, J L

    2009-10-01

    Multiple endocrine neoplasia (MEN) 2a consists on medullary thyroid carcinoma, pheochromocytoma and hyperparathyroidism. The identification of the RET proto-oncogene in 1993 has changed the prognosis of the disease. We have retrospectively studied the patients diagnosed of MEN 2a in our centre for the last 7 years in order to establish the most adequate age to undergo surgery. We present ten patients diagnosed with MEN 2a, whose ages ranged from 1.5 to 11 years old. Mean age at time of operation: 6,4 years An ultrasound study, calcitonin determinations and cathecholamines and urinary metanephrine levels were obtained before surgery. The surgical treatment is based on total total thyroidectomy, in selected cases lymph node resection in the central zone lf the neck. The most frequent RET mutation is the one affecting codon 634 (exon 10), which was found in children. Both of them had an alteration in codon 611 (exon11). No complications appeared after surgery and hospital discharge took place in the 2nd-4th day after surgery. Pathological findings were medullary thyroid microcarcinoma (MTMC) in 3 out of 10 patients, calcitonin preoperative tests were high in one of them. No tumoral cells were found in the lymph nodes. During the follow up period, 9 out of 10 from the operated patients, maintained normal calcitonin, CEA, PTH, calcium, cathecholamines and urinary metanephrine levels. Since there are 3 cases of MTC in patients between 3 and 6 years old, and diagnostic test data are not conclusive, we thoroughly recommend prophyilactic thyroidectomy at early ages, from 3 to 4 years old.

  14. Diagnosis by Endoscopy and Advanced Imaging of Barrett's Neoplasia.

    PubMed

    Swager, Anne-Fré; Curvers, Wouter L; Bergman, Jacques J

    Evaluation of patients with Barrett's esophagus (BE) using dye-based chromoendoscopy, optical chromoendoscopy, autofluorescence imaging, or confocal laser endomicroscopy does not significantly increase the number of patients with a diagnosis of early neoplasia compared with high-definition white light endoscopy (HD-WLE) with random biopsy analysis. These newer imaging techniques are not more effective in standard surveillance of patients with BE because the prevalence of early neoplasia is low and HD-WLE with random biopsy analysis detects most cases of neoplasia. The evaluation and treatment of patients with BE and early stage neoplasia should be centralized in tertiary referral centers, where procedures are performed under optimal conditions, by expert endoscopists. Lesions that require resection are almost always detected by HD-WLE, although advanced imaging techniques can detect additional flat lesions. However, these are of limited clinical significance because they are effectively eradicated by ablation therapy. No endoscopic imaging technique can reliably assess submucosal or lymphangio invasion. Endoscopic resection of early stage neoplasia in patients with BE is important for staging and management. Optical chromoendoscopy can also be used to evaluate lesions before endoscopic resection and in follow-up after successful ablation therapy.

  15. 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.

  16. Atypical epithelial hyperplasia of the breast: state of the art.

    PubMed

    Dion, Ludivine; Racin, Adelaïde; Brousse, Susie; Beltjens, Françoise; Cauchois, Aurélie; Levêque, Jean; Coutant, Charles; Lavoué, Vincent

    2016-09-01

    Atypical epithelial hyperplasia (AEH) of the breast is considered benign histological lesions with breast cancer risk. This review focuses on clinical signification and management of AEH that remains controversial. A review of published studies was performed using medline database. In this review, we fully describe the current evidence available. In particular, we describe 1) data from immunohistochemistry and molecular studies that suggest AEH is a precursor of breast cancer; 2) epidemiological studies demonstrate low rate of breast cancer in women with AEH; 3) surgical excision is necessary after diagnosis of AEH, such as lobular carcinoma in situ or atypical ductal hyperplasia, on core needle biopsy; 4) although current recommendations are evolving to fewer (if not no) excisions for flat epithelial with atypia and classic lobular neoplasia found on percutaneous biopsy (without radiologic indications for excision). Expert commentary: HEA management steel need prospective evidences, but recent retrospective data give some clue for less invasive management for some of HEA.

  17. Diagnosis and Medical Management of Ocular Surface Squamous Neoplasia.

    PubMed

    Sayed-Ahmed, Ibrahim O; Palioura, Sotiria; Galor, Anat; Karp, Carol L

    2017-01-01

    Topical chemotherapy has gained popularity among clinicians for the treatment of ocular surface squamous neoplasia (OSSN). The principal topical chemotherapy agents used in the management of OSSN are interferon-α2b, 5-fluorouracil, and mitomycin C. High-resolution optical coherence tomography (HR-OCT) is a non-invasive technique that can differentiate OSSN from other ocular surface lesions. This review highlights the current regimens and diagnostic modalities used in managing OSSN. A review of the literature was performed using the keywords "conjunctival intraepithelial neoplasia", "ocular surface squamous neoplasia", "optical coherence tomography", "interferon-α2b", "5-fluorouracil" and "mitomycin C". Topical chemotherapy for OSSN can be used as primary therapy, for chemoreduction prior to surgical excision, and postoperatively to prevent tumor recurrence. It has the advantage of treating microscopic disease as well as large tumors. HR-OCT provides an "optical biopsy" that can assist in diagnosis and guide management of OSSN lesions.

  18. Surgical intervention in children with multiple endocrine neoplasia type 2.

    PubMed

    Danko, Melissa E; Skinner, Michael A

    2006-06-01

    We provide a summary of the literature published in the past year addressing the surgical approach to multiple endocrine neoplasia type 2 in the pediatric population. The review focuses first on medullary thyroid carcinoma and performing prophylactic thyroidectomy for the prevention or cure of this disease. The timing and extent of surgery as well as additional surgical intervention for persistent or recurrent disease is discussed. Then the surgical management of hereditary pheochromocytoma is reviewed. Surgery is often the only treatment that can prevent or cure the endocrinopathies associated with multiple endocrine neoplasia type 2. Determining the proper timing and extent of surgical intervention in children affected with multiple endocrine neoplasia type 2 will lead to better outcomes and survival.

  19. Elective cesarean hysterectomy for treatment of cervical neoplasia. An update.

    PubMed

    Hoffman, M S; Roberts, W S; Fiorica, J V; Angel, J L; Finan, M A; Cavanagh, D

    1993-03-01

    From January 1, 1979, to March 31, 1991, 37 patients underwent elective cesarean hysterectomy for early cervical neoplasia. Thirty-four patients had cervical intraepithelial neoplasia III, and three patients had stage IA-1 squamous cell carcinoma of the cervix. Twenty-eight were primary cesarean sections; nine had obstetric indications. The mean operative time was 128 minutes; mean estimated blood loss was 1,400 mL. One patient experienced an intraoperative hemorrhage (3,500 mL). There were no other recognized intraoperative complications. Four significant postoperative complications included a vaginal cuff abscess, a wound dehiscence and pelvic abscess, one patient with febrile morbidity and an ileus and ligation with partial transection of a ureter. Patients were discharged on a mean of postoperative day 5.7. Although significant complications occurred, we believe that the noncompliant nature of our patient population justifies elective cesarean hysterectomy for treatment of cervical neoplasia.

  20. 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

  1. hpttg is over-expressed in pituitary adenomas and other primary epithelial neoplasias.

    PubMed

    Sáez, C; Japón, M A; Ramos-Morales, F; Romero, F; Segura, D I; Tortolero, M; Pintor-Toro, J A

    1999-09-23

    The role of oncogenes in pituitary tumorigenesis remains elusive since few genetic changes have been identified so far in pituitary tumors. Pituitary tumor-transforming gene (pttg) has been recently cloned from rat GH4 pituitary tumor cells. We have previously isolated and characterized hpttg from human thymus. In the present study, we analyse the expression of hpttg mRNA in a series of human pituitary adenomas. We show that hpttg is highly expressed in the majority of pituitary adenomas while only very low levels of mRNA can be detected in normal pituitary gland by Northern blot analysis. hPTTG protein was immunolocalized mainly in the cytoplasm of adenoma cells. Other common extra-cranial malignant tumors were also analysed by immunohistochemistry. Interestingly, strong hPTTG immunoreactivity was detected in most adenocarcinomas of mammary and pulmonary origins.

  2. Combination of widefield fluorescence imaging and nonlinear optical microscopy of oral epithelial neoplasia

    NASA Astrophysics Data System (ADS)

    Pal, Rahul; Edward, Kert; Brown, Tyra; Ma, Liang; Yang, Jinping; McCammon, Susan; Motamedi, Massoud; Vargas, Gracie

    2013-03-01

    Multiphoton Autofluorescence Microscopy (MPAM) and Second Harmonic Generation Microscopy (SHGM) have shown the potential for noninvasive assessment of oral precancers and cancers. We have explored a combination of these nonlinear optical microscopic imaging techniques with widefield fluorescence imaging to assess morphometry similar to that of pathologic evaluation as well as information from endogenous fluorophores, which are altered with neoplastic transformation. Widefield fluorescence revealed areas of interest corresponding to sites with precancers or early tumors, generally resulting in a decrease in green emission or increase in red emission. Subsequent microscopy revealed significant differences in morphology between normal, dysplastic/neoplastic mucosa for all layers. Combination of a widefield and a microscopic technique provides a novel approach for tissue morphometric analysis along with large area assessment of tissue autofluorescence properties.

  3. 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

  4. Colonic epithelial cell proliferation in a rat model of nongenotoxin-induced colonic neoplasia.

    PubMed

    Wilcox, D K; Higgins, J; Bertram, T A

    1992-09-01

    The effect on colonic cell proliferation of poligeenan, a nongenotoxic polysaccharide that induces colon tumors in rats, was compared with guar gum and carrageenan. Fischer 344 rats were fed a basal diet supplemented with carrageenan and poligeenan fibers for up to 91 days. The quantitative levels of proliferation, location of the proliferating cells, and the ability of the mucosa to readapt by removing the experimental fibers from the diet were tested. The mucosal epithelium exhibited a 5-fold increase in thymidine kinase activity in both the carrageenan and poligeenan groups. Proliferating cells appeared at the luminal surface only in the poligeenan-treated rats, and the number of proliferating cells in the upper third of the crypt increased 35-fold. A second and third set of animals were fed one of the three test diets for either 28 or 64 days, followed by a 28-day recovery period. Proliferation in the guar- and carrageenan-treated groups returned to basal levels. In poligeenan-treated rats, thymidine kinase levels, and proliferating cells in the upper third of the crypt remained 2- and 11-fold, respectively, above controls. The difference in recovery time between the poligeenan group and the others, and the luminal location of proliferating cells may prove useful as markers in understanding early events in the carcinogenic process induced by a nongenotoxin.

  5. Neurotensin receptor 1 overexpression in inflammatory bowel diseases and colitis-associated neoplasia

    PubMed Central

    Gui, Xianyong; Liu, Shuhong; Yan, Yuchu; Gao, Zuhua

    2013-01-01

    AIM: To explore the association of neurotensin receptor 1 (NTSR1) with inflammatory bowel diseases (IBD) and colitis-associated neoplasia. METHODS: NTSR1 was detected by immunohistochemistry in clinical samples of colonic mucosa with IBD colitis, colitis-associated raised low-grade dysplasia (LGD) including dysplasia-associated lesions or masses (DALMs, n = 18) and adenoma-like dysplastic polyps (ALDPs, n = 4), colitis-associated high-grade dysplasia (HGD, n = 11) and colitis-associated colorectal carcinoma (CACRC, n = 13), sporadic colorectal adenomatous polyp (SAP, n = 17), and sporadic colorectal carcinoma (SCRC, n = 12). The immunoreactivity of NTSR1 was semiquantitated (as negative, 1+, 2+, and 3+) and compared among different conditions. RESULTS: NTSR1 was not detected in normal mucosa but was expressed similarly in both active and inactive colitis. LGD showed a significantly stronger expression as compared with non-dysplastic colitic mucosa, with significantly more cases showing > 2+ intensity (68.75% in LGD vs 32.26% in nondysplastic mucosa, P = 0.001). However, no significant difference existed between DALMs and ALDPs. CACRC and HGD showed a further stronger expression, with significantly more cases showing 3+ intensity than that in LGD (61.54% vs 12.50% for CACRC vs LGD, P = 0.022; 58.33% vs 12.50% for CACRC/HGD vs LGD, P = 0.015). No significant difference existed between colitis-associated and non-colitic sporadic neoplasia. CONCLUSION: NTSR1 in colonic epithelial cells is overexpressed in IBD, in a stepwise fashion with sequential progress from inflammation to dysplasia and carcinoma. PMID:23901225

  6. Anal Neoplasia in Inflammatory Bowel Disease: Classification Proposal, Epidemiology, Carcinogenesis, and Risk Management Perspectives.

    PubMed

    Wisniewski, Andrew; Fléjou, Jean-Francois; Siproudhis, Laurent; Abramowitz, Laurent; Svrcek, Magali; Beaugerie, Laurent

    2017-08-01

    Patients with inflammatory bowel disease [IBD] may develop, similarly to individuals from general population, rare cases of human papilloma virus [HPV]-related anal canal squamous cell carcinoma [SCC] and intra-epithelial precursor lesions, as well as very rare cases of anal canal adenocarcinoma. Patients with chronic perianal Crohn's disease [CD] are at substantial risk of developing SCC or adenocarcinoma from the fistula-lining epithelium, as well as SCC or adenocarcinoma arising from chronic anorectal ulcerations or strictures. Based on this lesion stratification, we provide in this review tailored incidence estimates and we propose an IBD-specific classification of all types of anal neoplasia that may occur in patients with IBD. After reviewing putative carcinogenesis of all types of neoplasia, we conclude that HPV vaccination could reduce the incidence of HPV-related lesions, although an anal screening programme related to these lesions is not mandatory on the sole basis of IBD. By contrast, we point out that all patients with chronic perianal CD should be explored in depth, including biopsies under anaesthesia and fistula curettage when necessary, in case of any change in anal symptoms ─in particular new, increasing, unexplained pain. Finally, we conclude that there is an urgent need for elaborating and evaluating surveillance algorithms in patients with chronic perianal CD, in order to avoid cancers with late diagnosis and poor prognosis. Copyright © 2017 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  7. Stratified epithelium in prostatic adenocarcinoma: a mimic of high-grade prostatic intraepithelial neoplasia.

    PubMed

    Hameed, Omar; Humphrey, Peter A

    2006-07-01

    Typically glands of prostatic adenocarcinoma have a single cell lining, although stratification can be seen in invasive carcinomas with a cribriform architecture, including ductal carcinoma. The presence and diagnostic significance of stratified cells within non-cribriform carcinomatous prostatic glands has not been well addressed. The histomorphological features and immunohistochemical profile of cases of non-cribriform prostatic adenocarcinoma with stratified malignant glandular epithelium were analyzed. These cases were identified from needle biopsy cases from the consultation files of one of the authors and from a review of 150 consecutive in-house needle biopsy cases of prostatic adenocarcinoma. Immunohistochemistry was performed utilizing antibodies reactive against high molecular weight cytokeratin (34betaE12), p63 and alpha-methylacyl-coenzyme-A racemase (AMACR). A total of 8 cases were identified, including 2 from the 150 consecutive in-house cases (1.3%). In 4 cases, the focus with glands having stratified epithelium was the sole carcinomatous component in the biopsy, while such a component represented 5-30% of the invasive carcinoma seen elsewhere in the remaining cases. The main attribute in all these foci was the presence of glandular profiles lined by several layers of epithelial cells with cytological and architectural features resembling flat or tufted high-grade prostatic intraepithelial neoplasia, but lacking basal cells as confirmed by negative 34betaE12 and/or p63 immunostains in all cases. The AMACR staining profile of the stratified foci was variable, with 4 foci showing positivity, and 3 foci being negative, including two cases that displayed AMACR positivity in adjacent non-stratified prostatic adenocarcinoma. Prostatic adenocarcinoma with stratified malignant glandular epithelium can be identified in prostate needle biopsy samples harboring non-cribriform prostatic adenocarcinoma and resembles glands with high-grade prostatic

  8. Computed tomographic appearance of canine tonsillar neoplasia: 14 cases.

    PubMed

    Thierry, Florence; Longo, Maurizio; Pecceu, Evi; Zani, Davide D; Schwarz, Tobias

    2017-09-19

    The palatine tonsil is an uncommon site of oral canine neoplasia. For affected tonsils, squamous cell carcinoma is the most frequent type of neoplasia, followed by melanoma and lymphoma. Computed tomography (CT) is increasingly used for investigation of canine oropharyngeal pathology; however, limited information is available on the CT appearance of tonsillar neoplasms. Objectives of this retrospective descriptive case series were to characterize the CT features of canine tonsillar neoplasia and determine whether specific CT features differentiate nonneoplastic from neoplastic tonsils. Computed tomographic studies of 14 dogs diagnosed with tonsillar neoplasia were retrieved from two referral hospitals and reviewed by two observers. Diagnosis was based on histology or cytology. Carcinoma was diagnosed in 11 dogs, melanoma in two and lymphoma in one dog. Specific CT features of the tonsil and regional lymph nodes did not differentiate neoplastic from nonneoplastic tonsillar diseases, but regional lymph node CT features were useful for diagnosis in some cases. Marked enlargement (width ≥ 18 mm, 12/18), heterogeneity (16/18), and loss of the hypoattenuating hilus (18/18) of the medial retropharyngeal lymph node were common concomitant features of tonsillar neoplasia. The medial retropharyngeal and mandibular lymphadenomegaly was ipsilateral to the neoplastic tonsil in 8/12 and 6/9 dogs, respectively. Five dogs demonstrated little or no enlargement of the tonsil despite the associated metastatic lymphadenomegaly. Tonsillar neoplasia should therefore be considered as a differential diagnosis for dogs with CT evidence of isolated medial retropharyngeal lymphadenomegaly (regardless of normally sized tonsils), or of any enlarged tonsil with no associated lymphadenomegaly. © 2017 The Authors. Veterinary Radiology & Ultrasound published by Wiley Periodicals, Inc. on behalf of American College of Veterinary Radiology.

  9. 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

  10. Factors associated with conjunctival intraepithelial neoplasia: A case control study

    SciTech Connect

    Napora, C.; Cohen, E.J.; Genvert, G.I.; Presson, A.C.; Arentsen, J.J.; Eagle, R.C.; Laibson, P.R. )

    1990-01-01

    Familial and environmental factors may play a role in the development of conjunctival intraepithelial neoplasia (CIN). Nineteen patients with biopsy-proven CIN completed a questionnaire to evaluate possible predisposing factors. Nineteen age-matched and sex-matched controls completed questionnaires and received slit-lamp examinations. Factors associated with a relatively increased risk of developing CIN included exposure to petroleum products, heavy cigarette smoking, light hair and ocular pigmentation, and family origin in the British Isles, Austria or Switzerland. Non-office and nonprofessional workers were more likely to develop conjunctival intraepithelial neoplasia (p = .05), as were those who were not college graduates (p = .07).

  11. HIF2 and endocrine neoplasia: an evolving story.

    PubMed

    Maher, Eamonn R

    2013-06-01

    In this issue of Endocrine-Related Cancer, Toledo et al. report the identification of activating mutations in the HIF2 (EPAS1) transcription factor in a subset of sporadic pheochromocytomas and paragangliomas. These findings add significantly to an evolving and complex story of the role of hypoxic gene response pathways in human endocrine neoplasia.

  12. 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

  13. 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.

  14. Penile intraepithelial neoplasia--a veiled lesion in genitourinary medicine

    PubMed Central

    Jaleel, H.; Narouz, N.; Wade, A. A.; Allan, P. S.

    1999-01-01

    Penile intraepithelial neoplasia (PIN) is a clinically well known condition. However, its diagnosis is often difficult. We present four cases of PIN, seen in our department. Various histological patterns ranging from PIN I to PIN III were noted in these cases. 




 PMID:10754953

  15. [Comparative study on the effects of LEEP and laser CO(2) vaporization in cervical intraepithelial neoplasia II].

    PubMed

    Sun, Lu-Lu; Cao, Dong-Yan; Bian, Mei-Lu; Wei, Li-Hui; Yang, Jia-Xin; Yang, Li; Cheng, Ning-Hai; Wang, You-Fang; Cheng, Xue-Mei; Hu, Li-Jun; Lang, Jing-He; Shen, Keng

    2010-11-23

    to compare the effect and complications of loop electro-surgical excision procedure (LEEP) and laser CO(2) vaporization in the treatment of cervical intraepithelial neoplasia II. a total of 338 CINII women were recruited into this multi-center comparative study. The diagnosis was confirmed by histopathological examination for cervical epithelial cell abnormalities. And colposcopic examination was submitted to LEEP (n = 195) or laser CO(2) vaporization (n = 143) respectively. A post-treatment follow-up of 3, 6 and 12 months was carried out to compare the effect of two methods. among 195 women undergoing LEEP, the frequency of cure, persistent and recurrent CIN was 89.2% (n = 174), 4.1% (n = 8) and 3.6% (n = 7) respectively. And among 143 women receiving laser CO(2) vaporization, the frequency of cure, persistent and recurrent CIN was 86.7% (n = 124), 4.9% (n = 7) and 0.70% (n = 1) respectively. There was no statistical difference in cure rates, persistence or recurrence of CIN (P > 0.05). The recovery time, the operative frequency and intra-operative blood loss were significantly different in two groups. both LEEP and CO(2) vaporization are both effective and reliable for the treatment of cervical intraepithelial neoplasia II. However, pathological specimens may be harvested during LEEP. It is of vital importance to conduct preoperative colposcopic assessment and standard postoperative follow-ups.

  16. 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.

  17. 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

  18. 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%.

  19. Endoscopic Resection and Radiofrequency Ablation for Early Esophageal Neoplasia

    PubMed Central

    Belghazi, Kamar; Bergman, Jacques; Pouw, Roos E.

    2016-01-01

    Background In the last few decades, endoscopic treatment of early neoplastic lesions in the esophagus has established itself as a valid and less invasive alternative to surgical resection. Endoscopic resection (ER) is the cornerstone of endoscopic therapy. Next to the curative potential of ER, by removing neoplastic lesions, ER may also serve as a diagnostic tool. The relatively large tissue specimens obtained with ER enable accurate histological staging of a lesion, allowing for optimal decision-making for further patient management. ER was pioneered in Japan, mainly for the resection of gastric lesions and squamous esophageal neoplasia, and also Western countries have been increasingly implementing ER in the treatment of early gastroesophageal neoplasia, mostly associated with Barrett's esophagus (BE). In BE, however, there is still a risk of metachronous lesions in the remainder of the Barrett's after focal ER. Additional treatment of all Barrett's mucosa is therefore advised. Currently, the most effective method for this is by using radiofrequency ablation (RFA). This review will provide an overview of indications for ER and RFA. Key Messages and Conclusions Endoscopic management of early esophageal neoplasia is a safe and valid alternative to surgery and is nowadays the treatment of choice. ER is the mainstay of endoscopic management of early esophageal neoplasia since it allows for removal of neoplastic lesions and provides a large tissue specimen for histological evaluation. In case of early neoplasia in BE, focal ER should be complemented by eradication of the remaining Barrett's mucosa. RFA has proven to be a safe and effective modality to achieve complete eradication of Barrett's mucosa. PMID:27333327

  20. Effect of Helicobacter pylori on gastric epithelial cells

    PubMed Central

    Alzahrani, Shatha; Lina, Taslima T; Gonzalez, Jazmin; Pinchuk, Irina V; Beswick, Ellen J; Reyes, Victor E

    2014-01-01

    The gastrointestinal epithelium has cells with features that make them a powerful line of defense in innate mucosal immunity. Features that allow gastrointestinal epithelial cells to contribute in innate defense include cell barrier integrity, cell turnover, autophagy, and innate immune responses. Helicobacter pylori (H. pylori) is a spiral shape gram negative bacterium that selectively colonizes the gastric epithelium of more than half of the world’s population. The infection invariably becomes persistent due to highly specialized mechanisms that facilitate H. pylori’s avoidance of this initial line of host defense as well as adaptive immune mechanisms. The host response is thus unsuccessful in clearing the infection and as a result becomes established as a persistent infection promoting chronic inflammation. In some individuals the associated inflammation contributes to ulcerogenesis or neoplasia. H. pylori has an array of different strategies to interact intimately with epithelial cells and manipulate their cellular processes and functions. Among the multiple aspects that H. pylori affects in gastric epithelial cells are their distribution of epithelial junctions, DNA damage, apoptosis, proliferation, stimulation of cytokine production, and cell transformation. Some of these processes are initiated as a result of the activation of signaling mechanisms activated on binding of H. pylori to cell surface receptors or via soluble virulence factors that gain access to the epithelium. The multiple responses by the epithelium to the infection contribute to pathogenesis associated with H. pylori. PMID:25278677

  1. A prostatic intraepithelial neoplasia-dependent p27kip1 checkpoint induces senescence, inhibits cell proliferation and cancer progression

    PubMed Central

    Majumder, Pradip K.; Grisanzio, Chiara; O’Connell, Fionnuala; Barry, Marc; Brito, Joseph M.; Xu, Qing; Guney, Isil; Berger, Raanan; Herman, Paula; Bikoff, Rachel; Fedele, Giuseppe; Baek, Won-Ki; Wang, Shunyou; Ellwood-Yen, Katharine; Wu, Hong; Sawyers, Charles L.; Signoretti, Sabina; Hahn, William C.; Loda, Massimo; Sellers, William R.

    2008-01-01

    SUMMARY Transgenic expression of activated AKT1 in the murine prostate induces Prostatic Intraepithelial Neoplasia (PIN) that does not progress to invasive prostate cancer (CaP). In luminal epithelial cells of Akt-driven PIN we show the concomitant induction of p27kip1 and senescence. Genetic ablation of p27Kip1 led to down regulation of senescence markers and progression to cancer. In humans, p27Kip1 and senescence markers were elevated in PIN not associated with CaP, but were decreased and absent, respectively in cancer-associated PIN and in CaP. Importantly, p27Kip1 up-regulation in mouse and human in situ lesions did not depend upon mTOR or Akt activation but was instead specifically associated with alterations in cellular polarity, architecture and adhesion molecules. These data suggest that a p27Kip1-driven checkpoint limits progression of PIN to CaP. PMID:18691549

  2. 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

  3. Coincident inactivation of 14-3-3sigma and p16INK4a is an early event in vulval squamous neoplasia.

    PubMed

    Gasco, Milena; Sullivan, Alex; Repellin, Claire; Brooks, Louise; Farrell, Paul J; Tidy, John A; Dunne, Barbara; Gusterson, Barry; Evans, David J; Crook, Tim

    2002-03-14

    The structure and expression of 14-3-3 sigma(sigma) was analysed in squamous carcinomas (SCC) of the vulva and in the vulval pre-malignant lesion vulval intraepithelial neoplasia (VIN). Sequence analysis of the sigma coding region did not detect mutations in any case of SCC or VIN III and loss of heterozygosity (LOH) occurred in only 2 out of 27 informative cases. In contrast to the absence of genetic change, methylation-specific PCR (MSP) analysis revealed dense CpG methylation within the sigma gene in approximately 60% of cases of vulval SCC, but methylation was not detected in matched, normal epithelial tissue. Methylation was associated in all cases with reduced or absent expression of sigma mRNA. There was no correlation between sigma methylation and HPV or p53 status. Analysis of pre-malignant vulval intraepithelial neoplasia (VIN) revealed that sigma methylation was detectable early in neoplastic development. Co-incident methylation, accompanied by loss of expression, of sigma and p16INK4a was commonly detected in both SCC and VIN III, suggesting that epigenetic silencing of these two genes is an early and important event in vulval neoplasia.

  4. CTNNB1 (β-Catenin)-altered Neoplasia: A Review Focusing on Soft Tissue Neoplasms and Parenchymal Lesions of Uncertain Histogenesis.

    PubMed

    Agaimy, Abbas; Haller, Florian

    2016-01-01

    β-catenin (CTNNB1) is a key regulatory molecule of the Wnt signaling pathway, which is important for tissue homeostasis and regulation of cell proliferation, differentiation, and function. Abnormal stabilization and nuclear accumulation of β-catenin as a consequence of missense mutations or alternative molecular mechanisms occurs at a high frequency in a variety of epithelial cancers. In mesenchymal neoplasia, the role of β-catenin has been traditionally considered limited to desmoid-type fibromatosis. However, the spectrum of β-catenin-driven (β-catenin-altered) neoplasia of mesenchymal origin has been steadily widening to include, in addition to desmoid tumors, a variety of benign and intermediate-biology neoplasms of soft tissue (intranodal palisaded myofibroblastoma), head and neck (juvenile nasopharyngeal angiofibroma and sinonasal hemangiopericytoma/glomangiopericytoma), and ovarian (microcystic stromal tumor) origin. In addition, several old and newly reported distinctive site-specific β-catenin-driven parenchymal neoplasms of uncertain histogenesis have been well characterized in recent studies, including solid-pseudopapillary neoplasm of the pancreas and its recently described ovarian counterpart, sclerosing hemangioma of lung and calcifying nested stromal-epithelial tumor of the liver. This review addresses the most relevant pathobiological and differential diagnostic aspects of β-catenin-altered neoplasms with emphasis on site-specific histologic and biological variations. In addition, the morphologic overlap and analogy as well as distinctness between these uncommon tumors will be presented and discussed. Furthermore, a note is made on association of some of these lesions with hereditary tumor syndromes, in particular with the familial adenomatous polyposis coli.

  5. High-Resolution Optical Coherence Tomography Findings of Lisch Epithelial Corneal Dystrophy

    PubMed Central

    Pole, Cameron; Sise, Adam; Joag, Madhura; Galor, Anat; Bermudez-Magner, Jose Antonio; Dubovy, Sander; Karp, Carol L.

    2015-01-01

    Purpose To describe a case of Lisch epithelial corneal dystrophy (LECD) and present its unique characteristics on high-resolution optical coherence tomography (HR-OCT). Methods A 78-year-old man with whorled corneal epithelial opacities in the right eye was referred for evaluation of ocular surface squamous neoplasia. Clinical evaluation, photos, and HR-OCT images of involved cornea were obtained and scrapings of the affected cornea were sent for histopathologic analysis. Results Clinically the patient presented with a opalescent whirling epithelium in a linear pattern encroaching on the visual axis. HR-OCT showed normal thickness epithelial hyperreflectivity of involved cornea without stromal involvement, along with sharply demarcated borders of unaffected tissue. Histopathologic findings demonstrated vacuolated PAS-positive cells throughout the epithelial layers consistent with LECD. Conclusions HR-OCT was able to provide useful information to rule out ocular surface squamous neoplasia, and confirm the clinical impression of LECD at the time of clinical examination. HR-OCT shows promise as an adjunctive diagnostic tool for ocular surface lesions and pathologies. PMID:26764880

  6. 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.

  7. Quantification of confocal fluorescence microscopy for the detection of cervical intraepithelial neoplasia.

    PubMed

    Sheikhzadeh, Fahime; Ward, Rabab K; Carraro, Anita; Chen, Zhao Yang; van Niekerk, Dirk; Miller, Dianne; Ehlen, Tom; MacAulay, Calum E; Follen, Michele; Lane, Pierre M; Guillaud, Martial

    2015-10-24

    Cervical cancer remains a major health problem, especially in developing countries. Colposcopic examination is used to detect high-grade lesions in patients with a history of abnormal pap smears. New technologies are needed to improve the sensitivity and specificity of this technique. We propose to test the potential of fluorescence confocal microscopy to identify high-grade lesions. We examined the quantification of ex vivo confocal fluorescence microscopy to differentiate among normal cervical tissue, low-grade Cervical Intraepithelial Neoplasia (CIN), and high-grade CIN. We sought to (1) quantify nuclear morphology and tissue architecture features by analyzing images of cervical biopsies; and (2) determine the accuracy of high-grade CIN detection via confocal microscopy relative to the accuracy of detection by colposcopic impression. Forty-six biopsies obtained from colposcopically normal and abnormal cervical sites were evaluated. Confocal images were acquired at different depths from the epithelial surface and histological images were analyzed using in-house software. The features calculated from the confocal images compared well with those features obtained from the histological images and histopathological reviews of the specimens (obtained by a gynecologic pathologist). The correlations between two of these features (the nuclear-cytoplasmic ratio and the average of three nearest Delaunay-neighbors distance) and the grade of dysplasia were higher than that of colposcopic impression. The sensitivity of detecting high-grade dysplasia by analysing images collected at the surface of the epithelium, and at 15 and 30 μm below the epithelial surface were respectively 100, 100, and 92 %. Quantitative analysis of confocal fluorescence images showed its capacity for discriminating high-grade CIN lesions vs. low-grade CIN lesions and normal tissues, at different depth of imaging. This approach could be used to help clinicians identify high-grade CIN in clinical

  8. Hypertrophic herpes simplex simulating anal neoplasia in AIDS patients: report of five cases.

    PubMed

    Nadal, Sidney R; Calore, Edenilson E; Manzione, Carmen R; Horta, Sergio C; Ferreira, Aurea F; Almeida, Lis V

    2005-12-01

    Five patients (4 males; mean age, 46.4 years) with painful verrucous perianal lesions caused by herpes simplex virus are described. All patients had had AIDS for a long time and were using highly active antiretroviral therapy. CD4+ counts ranged from 73 to 370/mm3. All lesions were submitted to resection under subdural anesthesia. Histologic examinations revealed epithelial hyperplasia and dense inflammatory process, composed mainly of lymphocytes and plasma cells, extended just to the hypodermis. Immunohistochemistry was positive for herpes simplex virus Type 2 in four patients and for herpes simplex virus Type 1 in one patient, and did not detect human papillomavirus antigens. Three patients had recurrences after 3, 10, and 12 months. Resection was performed on two patients; one had a new recurrence after three months. Oral acyclovir eliminated the lesion in the third patient. The analysis of our patients suggests that herpes simplex virus, Types 1 and 2, may cause verrucous lesions simulating neoplasia in patients with AIDS using antiretroviral therapy.

  9. [Anal intraepithelial neoplasia (NIA) and infection with human papillomavirus (HPV) in anoreceptive patients].

    PubMed

    Charúa-Guindic, L; Esquivel-Ocampo, E A; Villanueva-Herrero, J A; Jiménez-Bobadilla, B; Muñoz-Cortés, S B; Leal-Tamez, M; Avendaño-Espinosa, O

    2009-01-01

    An association between human papilloma virus (HPV) infection and progression to anal intraepithelial neoplasia (AIN) and epidermoid cancer has been established. To know the prevalence of low and high grade AIN, as well as HPV infection in an anoreceptive patients group, infected or not, by human immunodeficiency virus (HIV). All patients with anoreceptive sexual relations were considered in this study. Patients who accepted anal citology and high definition anoscopy and biopsies with a follow-up not minor of 3 months were included. Forty-four patients were included: 40 male (90.9%) with average age of 31 years. Anal cytology showed inflammatory alterations in 21 patients (28%), low grade intraepithelial lesion in 23 (52%); there were not patients with high grade epithelial lesion. According to the high definition anoscopy, there were low grade intraepithelial lesion in 42 patients (95%) and high grade in 2 (5%). Biopsy showed low grade intraepithelial in 26 patients (59%), high grade in 4 (9%) and inflammatory alterations in 14 (32%). The prevalence of AIN and HPV infection was 68% in both diseases. The HIV infection was associated with the presence of high grade AIN (p=0.002, OR 47.7) There is a high prevalence of AIN and HPV infection between patients with anoreceptive sexual relations. The HIV infection is a risk factor for the development of high grade AIN.

  10. Diagnostic imaging of cervical intraepithelial neoplasia based on hematoxylin and eosin fluorescence.

    PubMed

    Castellanos, Mario R; Szerszen, Anita; Gundry, Stephen; Pirog, Edyta C; Maiman, Mitchell; Rajupet, Sritha; Gomez, John Paul; Davidov, Adi; Debata, Priya Ranjan; Banerjee, Probal; Fata, Jimmie E

    2015-07-25

    Pathological classification of cervical intraepithelial neoplasia (CIN) is problematic as it relies on subjective criteria. We developed an imaging method that uses spectroscopy to assess the fluorescent intensity of cervical biopsies derived directly from hematoxylin and eosin (H&E) stained tissues. Archived H&E slides were identified containing normal cervical tissue, CIN I, and CIN III cases, from a Community Hospital and an Academic Medical Center. Cases were obtained by consensus review of at least 2 senior pathologists. Images from H&E slides were captured first with bright field illumination and then with fluorescent illumination. We used a Zeiss Axio Observer Z1 microscope and an AxioVision 4.6.3-AP1 camera at excitation wavelength of 450-490 nm with emission captured at 515-565 nm. The 32-bit grayscale fluorescence images were used for image analysis. We reviewed 108 slides: 46 normal, 33 CIN I and 29 CIN III. Fluorescent intensity increased progressively in normal epithelial tissue as cells matured and advanced from the basal to superficial regions of the epithelium. In CIN I cases this change was less prominent as compared to normal. In high grade CIN lesions, there was a slight or no increase in fluorescent intensity. All groups examined were statistically different. Presently, there are no markers to help in classification of CIN I-III lesions. Our imaging method may complement standard H&E pathological review and provide objective criteria to support the CIN diagnosis.

  11. Patterns of persistent HPV infection after treatment for cervical intraepithelial neoplasia (CIN): A systematic review.

    PubMed

    Hoffman, Sarah R; Le, Tam; Lockhart, Alexandre; Sanusi, Ayodeji; Dal Santo, Leila; Davis, Meagan; McKinney, Dana A; Brown, Meagan; Poole, Charles; Willame, Corinne; Smith, Jennifer S

    2017-01-25

    A systematic review of the literature was conducted to determine the estimates of and definitions for human papillomavirus (HPV) persistence in women following treatment of cervical intra-epithelial neoplasia (CIN). A total of 45 studies presented data on post-treatment HPV persistence among 6,106 women. Most studies assessed HPV persistence after loop excision (42%), followed by conization (7%), cryotherapy (11%), laser treatment (4%), interferon-alpha, therapeutic vaccination, and photodynamic therapy (2% each) and mixed treatment (38%). Baseline HPV testing was conducted before or at treatment for most studies (96%). Follow-up HPV testing ranged from 1.5 to 80 months after baseline. Median HPV persistence tended to decrease with increasing follow-up time, declining from 27% at 3 months after treatment to 21% at 6 months, 15% at 12 months, and 10% at 24 months. Post-treatment HPV persistence estimates varied widely and were influenced by patient age, HPV-type, detection method, treatment method, and minimum HPV post-treatment testing interval. Loop excision and conization appeared to outperform cryotherapy procedures in terms of their ability to clear HPV infection. This systematic review provides evidence for the substantial heterogeneity in post-treatment HPV DNA testing practices and persistence estimates.

  12. Reconstituting development of pancreatic intraepithelial neoplasia from primary human pancreas duct cells

    PubMed Central

    Lee, Jonghyeob; Snyder, Emily R.; Liu, Yinghua; Gu, Xueying; Wang, Jing; Flowers, Brittany M.; Kim, Yoo Jung; Park, Sangbin; Szot, Gregory L.; Hruban, Ralph H.; Longacre, Teri A.; Kim, Seung K.

    2017-01-01

    Development of systems that reconstitute hallmark features of human pancreatic intraepithelial neoplasia (PanINs), the precursor to pancreatic ductal adenocarcinoma, could generate new strategies for early diagnosis and intervention. However, human cell-based PanIN models with defined mutations are unavailable. Here, we report that genetic modification of primary human pancreatic cells leads to development of lesions resembling native human PanINs. Primary human pancreas duct cells harbouring oncogenic KRAS and induced mutations in CDKN2A, SMAD4 and TP53 expand in vitro as epithelial spheres. After pancreatic transplantation, mutant clones form lesions histologically similar to native PanINs, including prominent stromal responses. Gene expression profiling reveals molecular similarities of mutant clones with native PanINs, and identifies potential PanIN biomarker candidates including Neuromedin U, a circulating peptide hormone. Prospective reconstitution of human PanIN development from primary cells provides experimental opportunities to investigate pancreas cancer development, progression and early-stage detection. PMID:28272465

  13. Morphological and morphometric measurements in colorectal mucosa of subjects at increased risk for colonic neoplasia.

    PubMed

    Richter, A; Yang, K; Richter, F; Lynch, H T; Lipkin, M

    1993-10-15

    Measurements of intermediate biomarkers have recently increased, attempting to provide useful information about cancer risk. We report morphological findings in rectal mucosal biopsies from patients at low risk and at high risk for colorectal cancer. Rectal biopsies were analyzed from fourteen Seventh-Day Adventist (SDA) subjects at low risk and from twenty-seven members of families with hereditary nonpolyposis colonic cancer (HNPCC) at higher risk. The following measurements were made on rectal crypts: length of crypts, numbers of cells, diameter of the surface, middle and base of the crypts and infiltration of inflammatory cells into the lamina propria. Findings indicated morphological differences in normal-appearing rectal mucosa of individuals in the HNPCC group compared with SDA subjects (P < 0.05). They included shorter crypts with fewer epithelial cells and increased cellular infiltration in the mucosa of HNPCC subjects compared with SDA subjects, suggesting minimal inflammation, and an early stage of crypt atrophy in the rectal mucosa of subjects at higher risk for colonic neoplasia.

  14. A notable accessory screening program for detection of cervical intraepithelial neoplasia.

    PubMed

    Tsai, H-T; Tsai, Y-M; Yang, S-F; Lee, C-H; Lin, L-Y; Lee, S; Wu, M-T

    2009-09-01

    Papanicolaou (Pap) smear test is implemented to detect cervical intraepithelial neoplasia (CIN) in Taiwan. However, the utility of that has limitations. High-risk human papillomavirus (HR-HPV) is an important risk factor in development of cervical cancer. In this study, we estimate the utility of HR-HPV testing in the screening of CIN. Firstly, 726 subjects were recruited and willing to prove cervical exfoliated epithelial cells for Pap smear screening and HR-HPV DNA testing. Subsequently, 205 of the eligible subjects with greater than or equal to CIN1 of Pap smear results were asked to perform histologic diagnosis that served as a gold standard for the estimation of the effects of both Pap smear and HR-HPV testing. The histology is significantly associated with HR-HPV infection, as well as significantly highly correlated with the individuals who have both Pap smear greater than or equal to CIN1 and positive HR-HPV infection but not significantly correlated with the individuals who only have Pap smear greater than or equal to CIN1 but without HR-HPV infection. Combinative surveillance of HR-HPV infection and Pap smear is a useful tool to detect and monitor precancerous lesions in the screening program. HR-HPV testing is a notable accessory screening program for detection of CIN in Taiwanese women.

  15. Induction of Cervical Neoplasia in the Mouse by Herpes Simplex Virus Type 2 DNA

    NASA Astrophysics Data System (ADS)

    Anthony, Donald D.; Budd Wentz, W.; Reagan, James W.; Heggie, Alfred D.

    1989-06-01

    Induction of cervical neoplasia in the mouse cervix by herpes simplex virus types 1 (HSV-1) and 2 (HSV-2) has been reported. The present study was done to determine if transfection with DNA of HSV-2 can induce carcinogenesis in this animal model. Genomic HSV-2 DNA was isolated from infected HEp-2 cells and separated from host cell DNA by cesium chloride density gradient centrifugation. The DNA was applied to mouse cervix for periods of 80-100 weeks. Experimental controls were treated with uninfected genomic HEp-2 cell DNA or with calf thymus DNA. Vaginal cytological preparations from all animals were examined monthly to detect epithelial abnormalities. Animals were sacrificed and histopathology studies were done when cellular changes indicative of premalignant or malignant lesions were seen on vaginal smears. Cytologic and histologic materials were coded and evaluated without knowledge of whether they were from animals treated with virus or control DNA. Premalignant and malignant cervical lesions similar to those that occur in women were detected in 61% of the histologic specimens obtained from animals exposed to HSV-2 DNA. The yield of invasive cancers was 21% in animals treated with HSV-2 DNA. No cancers were detected in mice treated with either HEp-2 or calf thymus DNA. Dysplasia was detected in only one of these control animals.

  16. Remodeling of the Epithelial-Connective Tissue Interface in Oral Epithelial Dysplasia as Visualized by Noninvasive 3D Imaging.

    PubMed

    Pal, Rahul; Shilagard, Tuya; Yang, Jinping; Villarreal, Paula; Brown, Tyra; Qiu, Suimin; McCammon, Susan; Resto, Vicente; Vargas, Gracie

    2016-08-15

    Early neoplastic features in oral epithelial dysplasia are first evident at the basal epithelium positioned at the epithelial-connective tissue interface (ECTI), separating the basal epithelium from the underlying lamina propria. The ECTI undergoes significant deformation in early neoplasia due to focal epithelial expansion and proteolytic remodeling of the lamina propria, but few studies have examined these changes. In the present study, we quantitated alterations in ECTI topography in dysplasia using in vivo volumetric multiphoton autofluorescence microscopy and second harmonic generation microscopy. The label-free method allows direct noninvasive visualization of the ECTI surface without perturbing the epithelium. An image-based parameter, "ECTI contour," is described that indicates deformation of the ECTI surface. ECTI contour was higher in dysplasia than control or inflamed specimens, indicating transition from flat to a deformed surface. Cellular parameters of nuclear area, nuclear density, coefficient of variation in nuclear area in the basal epithelium and collagen density in areas adjacent to ECTI were measured. ECTI contour differentiated dysplasia from control/benign mucosa with higher sensitivity and specificity than basal nuclear density or basal nuclear area, comparable with coefficient of variation in nuclear area and collagen density. The presented method offers a unique opportunity to study ECTI in intact mucosa with simultaneous assessment of cellular and extracellular matrix features, expanding opportunities for studies of early neoplastic events near this critical interface and potentially leading to development of new approaches for detecting neoplasia in vivo Cancer Res; 76(16); 4637-47. ©2016 AACR. ©2016 American Association for Cancer Research.

  17. 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

  18. Association between cysticercosis and neoplasia: a study based on autopsy findings.

    PubMed

    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.

  19. 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.

  20. Optimal management of low-risk gestational trophoblastic neoplasia.

    PubMed

    Goldstein, Donald P; Berkowitz, Ross S; Horowitz, Neil S

    2015-01-01

    Low-risk gestational trophoblastic neoplasia is a highly curable form of gestational trophoblastic neoplasia that arises largely from molar pregnancy and, on rare occasions, from other types of gestations. Risk is defined as the risk of developing drug resistance as determined by the WHO Prognostic Scoring System. All patients with non-metastatic disease and patients with risk scores <7 are considered to have low-risk disease. The sequential use of methotrexate and actinomycin D is associated with a complete remission rate of 80%. The most commonly utilized regimen for the treatment of patients resistant to single-agent chemotherapy is a multiagent regimen consisting of etoposide, methotrexate, actinomycin D, vincristine and cyclophosphamide. The measurement of human chorionic gonadotropin provides an accurate and reliable tumor marker for diagnosis, monitoring the effects of chemotherapy and follow-up to determine recurrence. Pregnancy is allowed after 12 months of normal serum tumor marker. Pregnancy outcomes are similar to those of normal population.

  1. [Focal epithelial hyperplasia].

    PubMed

    Vera-Iglesias, E; García-Arpa, M; Sánchez-Caminero, P; Romero-Aguilera, G; Cortina de la Calle, P

    2007-11-01

    Focal epithelial hyperplasia is a rare disease of the oral mucosa caused by the human papilloma virus (HPV). It appears as a benign epithelial growth, usually in the mucosa of the lower lip. It is mainly associated with HPV serotypes 13 and 32 and there is a clear racial predilection for the disease in Native Americans and Eskimos. We describe the case of a 17-year-old girl from Ecuador with multiple papular lesions in both lips that were clinically and histologically consistent with focal epithelial hyperplasia. Analysis by polymerase chain reaction detected HPV serotype 13.

  2. 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.

  3. 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

  4. 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.

  5. Early Cancer Detection at the Epithelial Surface.

    PubMed

    Rogalla, Stephan; Contag, Christopher H

    2015-01-01

    Malignant neoplastic lesions derived from epithelial tissue, carcinomas, account for 80% to 100% of all human cancers including some of the most deadly diseases such as cervical and non-small cell lung cancer. Many of these carcinomas present at readily accessible epithelial surfaces offering unique detection opportunities. Effective clinical management of carcinomas is enabled by early detection, at a time when full surgical resection is possible and before invasion of adjacent tissue or significant intravasation into blood vessels leading to metastasis. Good prognosis with long-term disease-free survival is more likely after early detection when progression is limited. At present, detection of carcinomas at epithelial surfaces largely relies on routine inspection with the naked eye (e.g., skin and oropharynx) or simple white light tools (e.g., cervix and colon). Emerging optical tools based on differential refraction, absorption, reflection, scattering, or fluorescence of carcinomas relative to normal tissues enable label-free visualization of neoplasia. However, the differences in intrinsic optical properties of normal and malignant tissues can be subtle, and relying on these may lead to high miss rates. Enhanced optical contrast offered by molecularly targeted agents can be used to improve early detection; and given that optical imaging and sensing tools can be readily combined, integrated systems that image over a range of scales, or detect multiple parameters, can be developed to aid in early detection. Diagnosis is, at present, made by histologic examination of tissue biopsies after identification of suspicious lesions. Miniature and handheld microscopic imaging tools have recently been developed, and integration of these tools with wide-field optical surveillance devices offers both rapid detection and confirmatory histologic examination at the point-of-care, that can provide guidance for biopsy and/or resection. A wide variety of targeted probe strategies

  6. Risk factors associated with Barrett's epithelial dysplasia.

    PubMed

    Fujita, Mikiko; Nakamura, Yuri; Kasashima, Saeko; Furukawa, Maiko; Misaka, Ryoichi; Nagahara, Hikaru

    2014-04-21

    To elucidate risk factors associated with dysplasia of short-segment Barrett's esophagus (BE). A total of 151 BE patients who underwent endoscopic examination from 2004 to 2008 in Aoyama Hospital, Tokyo Women's Medical University, Japan and whose diagnosis was confirmed from biopsy specimens were enrolled in the study. BE was diagnosed based on endoscopic findings of gastric-appearing mucosa or apparent columnar-lined esophagus proximal to the esophagogastric junction. Dysplasia was classified into three grades - mild, moderate and severe - according to the guidelines of the Vienna Classification System for gastrointestinal epithelial neoplasia. Anthropometric and biochemical data were analyzed to identify risk factors for BE dysplasia. The prevalence of Helicobacter pylori (H. pylori) infection and the expression of p53 by immunohistological staining were also investigated. Histological examination classified patients into three types: specialized columnar epithelium (SCE) (n = 65); junctional (n = 38); and gastric fundic (n = 48). The incidence of dysplasia or adenocarcinoma from BE of the SCE type was significantly higher than that of the other two types (P < 0.01). The univariate analysis revealed that sex, H. pylori infection, body weight, p53 overexpression, and low diastolic blood pressure (BP) were associated with BE dysplasia. In contrast, body mass index, waist circumference, metabolic syndrome complications, and variables related to glucose or lipid metabolism were not associated with dysplasia. Multivariate logistic analysis showed that overexpression of p53 [odds ratio (OR) = 13.1, P = 0.004], H. pylori infection (OR = 0.19, P = 0.066), and diastolic BP (OR = 0.87, P = 0.021) were independent risk factors for epithelial dysplasia in BE patients with the SCE type. Overexpression of p53 is a risk factor for dysplasia of BE, however, H. pylori infection and diastolic BP inversely associated with BE dysplasia might be protective.

  7. Surgical treatment of pancreatic endocrine tumors in multiple endocrine neoplasia type 1.

    PubMed

    Machado, Marcel Cerqueira Cesar

    2012-01-01

    Surgical approaches to pancreatic endocrine tumors associated with multiple endocrine neoplasia type 1 may differ greatly from those applied to sporadic pancreatic endocrine tumors. Presurgical diagnosis of multiple endocrine neoplasia type 1 is therefore crucial to plan a proper intervention. Of note, hyperparathyroidism/multiple endocrine neoplasia type 1 should be surgically treated before pancreatic endocrine tumors/multiple endocrine neoplasia type 1 resection, apart from insulinoma. Non-functioning pancreatic endocrine tumors/multiple endocrine neoplasia type 1 >1 cm have a high risk of malignancy and should be treated by a pancreatic resection associated with lymphadenectomy. The vast majority of patients with gastrinoma/multiple endocrine neoplasia type 1 present with tumor lesions at the duodenum, so the surgery of choice is subtotal or total pancreatoduodenectomy followed by regional lymphadenectomy. The usual surgical treatment for insulinoma/multiple endocrine neoplasia type 1 is distal pancreatectomy up to the mesenteric vein with or without spleen preservation, associated with enucleation of tumor lesions in the pancreatic head. Surgical procedures for glucagonomas, somatostatinomas, and vipomas/ multiple endocrine neoplasia type 1 are similar to those applied to sporadic pancreatic endocrine tumors. Some of these surgical strategies for pancreatic endocrine tumors/multiple endocrine neoplasia type 1 still remain controversial as to their proper extension and timing. Furthermore, surgical resection of single hepatic metastasis secondary to pancreatic endocrine tumors/multiple endocrine neoplasia type 1 may be curative and even in multiple liver metastases surgical resection is possible. Hepatic trans-arterial chemo-embolization is usually associated with surgical resection. Liver transplantation may be needed for select cases. Finally, pre-surgical clinical and genetic diagnosis of multiple endocrine neoplasia type 1 syndrome and localization of

  8. Spectroscopic characterization of oral epithelial dysplasia and squamous cell carcinoma using multiphoton autofluorescence micro-spectroscopy.

    PubMed

    Pal, Rahul; Edward, Kert; Ma, Liang; Qiu, Suimin; Vargas, Gracie

    2017-07-05

    Multiphoton autofluorescence microscopy (MPAM) has shown potential in identifying features that are directly related to tissue microstructural and biochemical changes throughout epithelial neoplasia. In this study, we evaluate the autofluorescence spectral characteristics of neoplastic epithelium in dysplasia and oral squamous cell carcinoma (OSCC) using multiphoton autofluorescence spectroscopy (MPAS) in an in vivo hamster model of oral neoplasia in order to identify unique signatures that could be used to delineate normal oral mucosa from neoplasia. A 9,10-dimethyl-1,2-benzanthracene (DMBA) hamster model of oral precancer and OSCC was used for in vivo MPAM and MPAS. Multiphoton Imaging and spectroscopy were performed with 780 nm excitation while a bandpass emission 450-650 nm was used for MPAM. Autofluorescence spectra was collected in the spectral window of 400-650 nm. MPAS with fluorescence excitation at 780 nm revealed an overall red shift of a primary blue-green peak (480-520 nm) that is attributed to NADH and FAD. In the case of oral squamous cell carcinoma (OSCC) and some high-grade dysplasia an additional prominent peak at 635 nm, attributed to PpIX was observed. The fluorescence intensity at 635 nm and an intensity ratio of the primary blue-green peak versus 635 nm peak, showed statistically significant difference between control and neoplastic tissue. Neoplastic transformation in the epithelium is known to alter the intracellular homeostasis of important tissue metabolites such as NADH, FAD, and PpIX, which was observed by MPAS in their native environment. A combination of deep tissue microscopy owing to higher penetration depth of multiphoton excitation and depth resolved spectroscopy could prove to be invaluable in identification of cytologic as well as biomolecular spectral characteristic of oral epithelial neoplasia. Lasers Surg. Med. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  9. Development of a Reactive Stroma Associated with Prostatic Intraepithelial Neoplasia in EAF2 Deficient Mice

    PubMed Central

    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. PMID:24260246

  10. 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

  11. Vaginal cancer in a patient treated for cervical intraepithelial neoplasia (CIN 3): case report.

    PubMed

    Androutsopoulos, G; Adonakis, G; Ravazoula, P; Kourounis, G

    2006-01-01

    In 1% to 3% of patients with cervical intraepithelial neoplasia (CIN), vaginal intraepithelial neoplasia (VAIN) will either coexist or occur at a later date. The time interval from an earlier diagnosis of CIN 3 to a current diagnosis of VAIN 3 varies from two to 17 years. Invasive vaginal cancer occurred in a woman five years after total abdominal hysterectomy for cervical intraepithelial neoplasia. In women who have undergone total hysterectomy for cervical intraepithelial neoplasia or cervical cancer, postoperative cytologic and colposcopic follow-up of the vagina is necessary.

  12. 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.

  13. Expression of activation-induced cytidine deaminase in oral epithelial dysplasia and oral squamous cell carcinoma.

    PubMed

    Miyazaki, Yuji; Fujinami, Masahiro; Inoue, Harumi; Kikuchi, Kentaro; Ide, Fumio; Kusama, Kaoru

    2013-01-01

    Oral epithelial dysplasia is thought to be a precursor state of carcinogenesis and may harbor gene alterations. Recently, it was reported that gene editing enzyme, activation-induced cytidine deaminase (AID), is expressed in precursor and cancer epithelial cells during carcinogenesis associated with chronic inflammation/infection and that this enzyme induces mutation of tumor-suppressor genes. Thus, AID may have a role in carcinogenesis via oral epithelial dysplasia. In this study, we classified oral mucosal epithelium exhibiting epithelial dysplasia as squamous intraepithelial neoplasia (SIN) grades 1-3, according to the 2005 World Health Organization classification, and used immunohistochemical techniques to examine AID expression in oral mucosal epithelium exhibiting SIN and oral cancer tissues. AID was observed in prickle cells in oral mucosal epithelium with epithelial dysplasia and in oral cancer cells. Additionally, to investigate the mechanism of AID expression and its role in cancer progression, we incubated the oral cancer cell line HSC-2 with inflammatory cytokines. In the HSC-2 cell line, AID expression was enhanced by TNF-α via NF-κB activation and promoted expression of N-cadherin by regulating Snail expression. These findings suggest that AID has a role in the development of oral epithelial dysplasia and promotes progression of oral cancer.

  14. Oral epithelial dysplasia classification systems: predictive value, utility, weaknesses and scope for improvement.

    PubMed

    Warnakulasuriya, S; Reibel, J; Bouquot, J; Dabelsteen, E

    2008-03-01

    At a workshop coordinated by the WHO Collaborating Centre for Oral Cancer and Precancer in the United Kingdom issues related to potentially malignant disorders of the oral cavity were discussed by an expert group. The consensus views of the Working Group are presented in a series of papers. In this report, we review the oral epithelial dysplasia classification systems. The three classification schemes [oral epithelial dysplasia scoring system, squamous intraepithelial neoplasia and Ljubljana classification] were presented and the Working Group recommended epithelial dysplasia grading for routine use. Although most oral pathologists possibly recognize and accept the criteria for grading epithelial dysplasia, firstly based on architectural features and then of cytology, there is great variability in their interpretation of the presence, degree and significance of the individual criteria. Several studies have shown great interexaminer and intraexaminer variability in the assessment of the presence or absence and the grade of oral epithelial dysplasia. The Working Group considered the two class classification (no/questionable/ mild - low risk; moderate or severe - implying high risk) and was of the view that reducing the number of choices from 3 to 2 may increase the likelihood of agreement between pathologists. The utility of this need to be tested in future studies. The variables that are likely to affect oral epithelial dysplasia scoring were discussed and are outlined here; these need to be researched in longitudinal studies to explore the biological significance of a low-risk or high-risk dysplasia.

  15. Multicolor immunofluorescence reveals that p63- and/or K5-positive progenitor cells contribute to normal breast epithelium and usual ductal hyperplasia but not to low-grade intraepithelial neoplasia of the breast.

    PubMed

    Boecker, Werner; Stenman, Göran; Schroeder, Tina; Schumacher, Udo; Loening, Thomas; Stahnke, Lisa; Löhnert, Catharina; Siering, Robert Michael; Kuper, Arthur; Samoilova, Vera; Tiemann, Markus; Korsching, Eberhard; Buchwalow, Igor

    2017-03-16

    We contend that knowledge about the cellular composition of normal breast epithelium is a prerequisite for understanding proliferative breast disease. Against this background, we used multicolor immunofluorescence to study normal breast epithelium and two types of intraepithelial proliferative breast lesion for expression of the p63, basal keratin K5, glandular keratin K8/18, SMA, ER-alpha, and Ki67. We studied eight normal breast epithelium samples, 12 cases of usual ductal hyperplasia, and 33 cases of low-grade intraepithelial neoplasia (9 flat epithelial atypia, 14 low-grade ductal carcinoma in situ and 10 cases of lobular neoplasia). Usual ductal hyperplasia showed striking similarity to normal luminal breast epithelium including p63+ and/or K5+ luminal progenitor cells and the full spectrum of luminal progeny cells. In normal breast epithelium and usual ductal hyperplasia, expression of ER-alpha was associated with lack of expression of the proliferation antigen Ki67. In contrast, we found in both types of low-grade intraepithelial neoplasia robust expression of keratin K8/18 and a positive association between ER-alpha and Ki67 expression. However, these lesions were consistently negative for p63 and/or K5. Our observational study supports the view that usual ductal hyperplasia and low-grade intraepithelial neoplasia are different entities rather than part of a spectrum of the same disease. We propose a new operational model of cell differentiation that may serve to better understand correlations between normal breast epithelium and proliferative breast diseases. From our data we conclude that p63+ and/or K5+ progenitor cells contribute to maintenance of normal epithelium and usual ductal hyperplasia, but not to low-grade intraepithelial neoplasia of the breast.

  16. Calcium/Ask1/MKK7/JNK2/c-Src signalling cascade mediates disruption of intestinal epithelial tight junctions by dextran sulfate sodium.

    PubMed

    Samak, Geetha; Chaudhry, Kamaljit K; Gangwar, Ruchika; Narayanan, Damodaran; Jaggar, Jonathan H; Rao, RadhaKrishna

    2015-02-01

    Disruption of intestinal epithelial tight junctions is an important event in the pathogenesis of ulcerative colitis. Dextran sodium sulfate (DSS) induces colitis in mice with symptoms similar to ulcerative colitis. However, the mechanism of DSS-induced colitis is unknown. We investigated the mechanism of DSS-induced disruption of intestinal epithelial tight junctions and barrier dysfunction in Caco-2 cell monolayers in vitro and mouse colon in vivo. DSS treatment resulted in disruption of tight junctions, adherens junctions and actin cytoskeleton leading to barrier dysfunction in Caco-2 cell monolayers. DSS induced a rapid activation of c-Jun N-terminal kinase (JNK), and the inhibition or knockdown of JNK2 attenuated DSS-induced tight junction disruption and barrier dysfunction. In mice, DSS administration for 4 days caused redistribution of tight junction and adherens junction proteins from the epithelial junctions, which was blocked by JNK inhibitor. In Caco-2 cell monolayers, DSS increased intracellular Ca(2+) concentration, and depletion of intracellular Ca(2+) by 1,2-bis-(o-aminophenoxy)ethane-N,N,N',N'-tetra-acetic acid tetrakis(acetoxymethyl ester) (BAPTA/AM) or thapsigargin attenuated DSS-induced JNK activation, tight junction disruption and barrier dysfunction. Knockdown of apoptosis signal-regulated kinase 1 (Ask1) or MKK7 blocked DSS-induced tight junction disruption and barrier dysfunction. DSS activated c-Src by a Ca2+ and JNK-dependent mechanism. Inhibition of Src kinase activity or knockdown of c-Src blocked DSS-induced tight junction disruption and barrier dysfunction. DSS increased tyrosine phosphorylation of occludin, zonula occludens-1 (ZO-1), E-cadherin and β-catenin. SP600125 abrogated DSS-induced tyrosine phosphorylation of junctional proteins. Recombinant JNK2 induced threonine phosphorylation and auto-phosphorylation of c-Src. The present study demonstrates that Ca(2+)/Ask1/MKK7/JNK2/cSrc signalling cascade mediates DSS-induced tight

  17. Calcium-Ask1-MKK7-JNK2-c-Src Signaling Cascade Mediates Disruption of Intestinal Epithelial Tight Junctions by Dextran Sulfate Sodium

    PubMed Central

    Samak, Geetha; Chaudhry, Kamaljit K.; Gangwar, Ruchika; Narayanan, Damodaran; Jaggar, Jonathan H.; Rao, RadhaKrishna

    2015-01-01

    Disruption of intestinal epithelial tight junctions is an important event in the pathogenesis of ulcerative colitis. Dextran sodium sulfate (DSS) induces colitis in mice with the symptoms similar to ulcerative colitis. However, the mechanism of DSS-induced colitis is unknown. We investigated the mechanism of DSS-induced disruption of intestinal epithelial tight junctions and barrier dysfunction in Caco-2 cell monolayers in vitro and mouse colon in vivo. DSS treatment resulted in disruption of tight junctions, adherens junctions and actin cytoskeleton leading to barrier dysfunction in Caco-2 cell monolayers. DSS induced a rapid activation of c-jun N-terminal kinase (JNK), and the inhibition or knockdown of JNK2 attenuated DSS-induced tight junction disruption and barrier dysfunction. In mice, DSS administration for 4 days caused redistribution of tight junction and adherens junction proteins from the epithelial junctions, which was blocked by JNK inhibitor. In Caco-2 cell monolayers, DSS increased intracellular Ca2+ concentration, and depletion of intracellular Ca2+ by BAPTA or thapsigargin attenuated DSS-induced JNK activation, tight junction disruption and barrier dysfunction. Knockdown of Ask1 or MKK7 blocked DSS-induced tight junction disruption and barrier dysfunction. DSS activated c-Src by a Ca2+ and JNK-dependent mechanism. Inhibition of Src kinase activity or knockdown of c-Src blocked DSS-induced tight junction disruption and barrier dysfunction. DSS increased Tyr-phosphorylation of occludin, ZO-1, E-cadherin and β-catenin. SP600125 abrogated DSS-induced Tyr-phosphorylation of junctional proteins. Recombinant JNK2 induced threonine phosphorylation and auto phosphorylation of c-Src. This study demonstrates that Ca2+-Ask1-MKK7-JNK2-cSrc signaling cascade mediates DSS-induced tight junction disruption and barrier dysfunction. PMID:25377781

  18. Adherence to therapy for Barrett's esophagus-associated neoplasia.

    PubMed

    Cassani, Lisa; Slaughter, James C; Yachimski, Patrick

    2016-02-01

    Multiple endoscopic sessions may be necessary for treatment and surveillance of Barrett's esophagus (BE)-associated neoplasia. Adherence to an endoscopic therapeutic regimen is important for longitudinal management of BE. The objective of this study was to identify the factors associated with adherence to therapy for BE-associated neoplasia. We retrospectively identified patients with BE whom were referred to a tertiary center for endoscopic mucosal resection (EMR) or radiofrequency ablation (RFA) between 2009 and 2012. Demographic and clinical data were extracted from the medical record. We had 69 subjects meet our inclusion criteria. Referral diagnosis was low-grade dysplasia in 9 (13%) subjects, high-grade dysplasia in 33 (48%) subjects and adenocarcinoma in 26 (38%) subjects. The majority (55%) lived more than 100 miles from the treatment center. The primary third-party payer was US Medicare for 54% of the subjects and private insurance for 36% of them; 45% of the subjects were seen in the clinic by the treating endoscopist, prior to endoscopic therapy and 71% underwent EMR as the initial treatment, while 29% underwent RFA without prior EMR. We found that 72% of subjects were adherent to therapy, including: 23 (33%) completing endoscopic therapy with documented post-treatment surveillance, 18 (26%) with ongoing endoscopic therapy, and 9 (13%) whom underwent esophagectomy. Subjects seen in gastroenterology clinical consultation were significantly more likely to demonstrate adherence than those referred for open access endoscopy (Lasso OR 2.31). Patients seen in a clinical consultation prior to endoscopic therapy for BE-associated neoplasia were more likely to demonstrate treatment adherence, compared to patients referred for open-access endoscopy. A clinic visit prior to therapy may define expectations regarding treatment course and increase the likelihood of patient adherence.

  19. Male pattern baldness and risk of colorectal neoplasia.

    PubMed

    Keum, N; Cao, Y; Lee, D H; Park, S M; Rosner, B; Fuchs, C S; Wu, K; Giovannucci, E L

    2016-01-12

    Male pattern baldness is positively associated with androgens as well as insulin-like growth factor 1 (IGF-1) and insulin, all of which are implicated in pathogenesis of colorectal neoplasia. From 1992 through 2010, we prospectively followed participants in the Health Professionals Follow-Up Study. Hair pattern at age 45 years was assessed at baseline with five image categories (no baldness, frontal-only baldness, frontal-plus-mild-vertex baldness, frontal-plus-moderate-vertex baldness, and frontal-plus-severe-vertex baldness). Cancer analysis included 32 782 men and used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Restricted to men who underwent at least one endoscopy over the study period, adenoma analysis included 29 770 men and used logistic regressions for clustered data to estimate odds ratios (ORs) and 95% CIs. Over the mean follow-up of 15.6 years, 710 cases of colorectal cancer (478 for colon, 152 for rectum, and 80 unknown site) developed. Significantly increased risks associated with frontal-only baldness and frontal-plus-mild-vertex baldness relative to no baldness were observed for colon cancer with respective HR being 1.29 (95% CI, 1.03-1.62) and 1.31 (95% CI, 1.01-1.70). Over the 19-year study period, 3526 cases of colorectal adenoma were detected. Evidence for an increased risk of colorectal adenoma relative to no baldness was significant with frontal-only baldness (OR, 1.16; 95% CI, 1.06-1.26) and borderline insignificant with frontal-plus-severe-vertex baldness (OR, 1.14; 95% CI, 0.98-1.33). Subtypes of male pattern baldness at age 45 years were positively associated with colorectal neoplasia. Future studies are warranted to confirm our results and to determine the predictive value of male pattern baldness to identify those at high risk for colorectal neoplasia.

  20. Photodynamic therapy of cervical intraepithelial neoplasia using hexaminolevulinate and methylaminolevulinate

    NASA Astrophysics Data System (ADS)

    Soergel, Philipp; Staboulidou, Ismini; Hertel, Herrmann; Schippert, Cordula; Hillemanns, Peter

    2009-06-01

    Cervical intraepithelial neoplasia (CIN) is the precursor of invasive cervical cancer. Previous studies indicated that photodynamic therapy (PDT) represents an effective treatment modality in CIN. In 28 patients with CIN 1 - 3, 1 - 2 cycles of PDT were conducted using hexaminolevulinate (HAL) or methylaminolevulinate (MAL) and a special light delivery system. After 6 months, biopsies were obtained to assess response. The overall response rate for complete or partial response was 65%. Photodynamic therapy using new ALA esters is effective and may offer unique advantages in the therapy of CIN.

  1. Endocrine surgical aspects of multiple endocrine neoplasia syndromes in children.

    PubMed

    Harrison, Barney

    2007-01-01

    All patients diagnosed with medullary thyroid carcinoma (MTC) should undergo RET mutation analysis to exclude familial disease - multiple endocrine neoplasia (MEN)-2A and -2B and familial medullary thyroid carcinoma (FMTC). In young patients at risk of genetically determined MTC, the key to a good outcome is an appropriate first operation, and this will depend upon the codon mutation, patient age, calcitonin level and disease extent at presentation. When MTC has already developed, a therapeutic intervention is required. The thyroid, pituitary, adrenal, parathyroid and pancreatic components of MEN-1 and -2 require close collaboration of a specialist and experienced multidisciplinary team.

  2. 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

  3. Invasive Ocular Surface Squamous Neoplasia Masquerading as Nodular Scleritis.

    PubMed

    Sharma, Medha; Sundar, Dheepak; Vanathi, Murugesan; Meel, Rachna; Kashyap, Seema; Chawla, Rohan; Tandon, Radhika

    The authors report a rare case of ocular surface squamous neoplasia with intraocular involvement that had an initial masquerade presentation of recurrent anterior nodular scleritis. A 35-year-old male patient presented with right eye recurrent anterior nodular scleritis for which a lamellar patch graft was done. Two months later, the patient presented with recurrence of symptoms. Histopathology review revealed the presence of well-differentiated squamous cell malignancy. A high index of suspicion for malignancy is required in such cases when they do not respond to conventional therapy.

  4. 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. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Genetics Home Reference: X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia

    MedlinePlus

    ... X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia Printable PDF Open All Close ... X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia (typically known by the acronym ...

  6. Galectins in epithelial functions

    PubMed Central

    Viguier, Mireille; Advedissian, Tamara; Delacour, Delphine; Poirier, Françoise; Deshayes, Frédérique

    2014-01-01

    Galectins are a family of animal lectins comprising 15 members in vertebrates. These proteins are involved in many biological processes including epithelial homeostasis and tumor progression by displaying intracellular and extracellular activities. Hence Galectins can be found either in the cytoplasm or the nucleus, associated with membranes or in the extracellular matrix. Current studies aim at understanding the roles of Galectins in cell-cell and cell-matrix adhesion, cellular polarity and motility. This review discusses recent progress in defining the specificities and mechanisms of action of Galectins as cell regulators in epithelial cells. Physiological, cellular and molecular aspects of Galectin specificities will be treated successively. PMID:25097826

  7. When pathological and radiological correlation is achieved, excision of fibroadenoma with lobular neoplasia on core biopsy is not warranted.

    PubMed

    Fives, C; O'Neill, C J; Murphy, R; Corrigan, M A; O'Sullivan, M J; Feeley, L; Bennett, M W; O'Connell, F; Browne, T J

    2016-12-01

    The diagnosis and management of lobular neoplasia (LN) including lobular carcinoma in situ (LCIS) and atypical lobular hyperplasia (ALH) remains controversial. Current management options after a core needle biopsy (CNB) with lobular neoplasia (LN) incorporating both ALH and LCIS include excision biopsy or careful clinical and radiologic follow up. A retrospective analysis of the surgical database at Cork University Hospital was performed to identify all core needle biopsies from January 1st 2010 to 31st December 2013 with a diagnosis of FA who subsequently underwent surgical excision biopsy. All cases with associated LN including ALH and classical LCIS were selected. We excluded cases with coexistent ductal carcinoma in situ (DCIS), invasive carcinoma, LN associated with necrosis, pleomorphic lobular carcinoma in situ (PLCIS) or lesions which would require excision in their own right (papilloma, radial scar, atypical ductal hyperplasia (ADH) or flat epithelial atypia (FEA)). Cases in which the radiologic targeted mass was discordant with a diagnosis of FA were also excluded. 2878 consecutive CNB with a diagnosis of FA were identified. 25 cases had a diagnosis of concomitant ALH or classical LCIS. Our study cohort consisted of 21 women with a mean age 53 years (age range 41-70 years). The core biopsy diagnosis was of LCIS and FA in 16 cases and ALH and FA in 5 cases. On excision biopsy, a FA was confirmed in all 21 cases. In addition to the FA, residual LCIS was present in 14 cases with residual ALH in 2 cases. One of the twenty-one cases (4.8%) was upgraded to invasive ductal carcinoma on excision. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. p53 codon 72 polymorphism in vulval cancer and vulval intraepithelial neoplasia

    PubMed Central

    Rosenthal, A N; Ryan, A; Hopster, D; Jacobs, I J

    2000-01-01

    p53 codon 72 polymorphism was analysed in UK women with human papillomavirus (HPV)-associated vulval intraepithelial neoplasia and vulval squamous cell carcinoma. Arginine homozygotes were significantly less common in either group compared with controls. We conclude that the arginine polymorphism may confer protection against the development of HPV-associated vulval neoplasia. © 2000 Cancer Research Campaign PMID:11044351

  9. [High-grade prostatic intraepithelial neoplasia: state-of-the-art].

    PubMed

    Allina, D O; Andreeva, Iu Iu; Zavalishina, L E; Kekeeva, T V; Frank, G A

    2015-01-01

    According to current views, high-grade prostatic intraepithelial neoplasia is the most likely precursor of prostate adenocarcinoma. This review gives the latest data of genetic, proteomic, and morphological analyses of this neoplasia and touches upon the probems that might arise when searching for new markers for differential diagnosis and prognosis estimation.

  10. Novel dual-function CellDetect® staining technology: wedding morphology and tinctorial discrimination to detect cervical neoplasia

    PubMed Central

    2010-01-01

    Background A persistent goal of oncologic histochemistry is to microscopically identify neoplasia tinctorially. Consequently, the newly developed CellDetect® staining technology, that appears to exhibit this property, warrants clinical evaluation. The objective of this study was to compare the diagnostic results using CellDetect® to the outcomes of standard microscopic examination based on hematoxylin and eosin (H&E) staining for the recognition of different squamous epithelial phenotypes of the uterine cervix. Methods Pairs of adjacent sections were made from 60 cervical biopsy cases that were diagnosed originally as either normal or neoplastic (CIN, SCC). One section of the pair was stained for H&E; the second section, with CellDetect®. Based on the examination of these pairs by two experienced pathologists, we investigated the following issues:(1) diagnostic agreement between the pathologists on each pair; (2) agreement between H&E and CellDetect® for each pair (3) tinctorial characteristics in micro-regions (n = 130) evaluated as either normal, reactive or neoplastic. Results Qualitatively, CellDetect®-stained preparations displayed cyto-morphological detail comparable to H&E images. Tinctorially, non-neoplastic cells appeared green/blue when stained withCellDetect®, contrasting with cytologically neoplastic foci, where cells of every grade were red/magenta in color. Due to these tinctorial characteristics, even small foci of neoplasia could be readily distinguished that were inconspicuous on H&E at low magnification. In some instances, this prompted re-examination of the H&E and revision of the diagnosis. Quantitatively, we found that despite diagnostic variation between pathologists, in about 3% of the cases, each pathologist made the same diagnosis regardless of whether CellDetect® or H&E was used, i.e. there was 100% self-agreement for each pathologist between stains. Particularly noteworthy was the finding of a 0% false negative rate, coupled with a

  11. 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.

  12. 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.

  13. New perspectives on neoplasia and the RNA world.

    PubMed

    Hall, Peter A; Russell, Se Hilary

    2005-06-01

    Key tenets of modern biology are the central place of protein in cell regulation and the flow of genetic information from DNA to RNA to protein. However, it is becoming increasingly apparent that genomes are much more complex than hitherto thought with remarkably complex regulatory systems. The notion that the fraction of the genome involved in coding protein is all that matters is increasingly being questioned as the roles of non-coding RNA (ncRNA) in cellular systems becomes recognised. The RNA world, including microRNA (miRNA), small inhibitory RNA (siRNA) and other RNA species, are now recognised as being crucial for the regulation of chromatin structure, gene expression, mRNA processing and splicing, mRNA stability and translational control. Furthermore such ncRNA systems may be perturbed in disease states and most notably in neoplasia, including in haematological malignancies. Here the burgeoning evidence for a role of miRNA in neoplasia is reviewed and the importance of understanding the RNA world emphasised.

  14. 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

  15. Aortic chondroid neoplasia in two Labrador Retriever dogs.

    PubMed

    Kohnken, R; Durham, J A; Premanandan, C; Scansen, B A

    2015-12-01

    In the same week, two Labrador Retriever dogs presented to The Ohio State University Veterinary Medical Center for cardiac evaluation. The presenting signs in both dogs included: weight loss, weakness, lethargy, and decreased femoral pulses. The first dog presented in cardiogenic shock and biventricular congestive heart failure, which initially responded to treatment; however, the dog was euthanized due to deteriorating clinical condition. In contrast, the second dog had a milder clinical course without signs of congestive heart failure, and remained stable over the 2-month period of clinical evaluation prior to euthanasia. Echocardiographic evaluation revealed a dilated cardiomyopathy phenotype in the first dog, while a space-occupying intraluminal mass originating at the aortic valve with preserved left ventricular systolic function was observed in the second dog. At autopsy, each dog had a large obstructive luminal mass affecting the ascending aorta and arch. Histopathology revealed that the mass in the first dog was consistent with a benign chondroma, while in the second dog the morphologic characteristics, mitotic activity, and infiltrative growth justified a diagnosis of chondrosarcoma. This report presents the contrasting clinical disease progression and findings in two dogs with aortic neoplasia, with a proposed pathogenesis of cardiac failure secondary to aortic neoplasia.

  16. [Treatment of cervical intraepithelial neoplasia using the CO2 laser].

    PubMed

    Trejo Solorzano, O; González Iñiguez, R

    1991-04-01

    The use of laser therapy in CIN, is a practical method that has revolutionized the treatment of a very common pathology, that is the cervical neoplasia in its early stages. 86 patients with different stages of cervical intraepithelial neoplasia, were studied. Patients in groups I (45 patients) y II (28 patients), were submitted to a vaporization crater of the whole transformation zone because of having the cervical canal free of lesion. In group III (13 patients), a cylinder of the cervix was done to perform histological study, whether the cervical canal was compromised or not. The cytology control results for group I were excellent; from (45 patients) who came to 3-month check-up 79.1% of the whole presented negative II. For group II (28 patients), in first pap smear two patients (7.1%) had CIN, the rest of smears were reported 66% negative II, and in the 30.6% negative I. For the group III 14.2% (5 patients) of the whole had abnormal results, the rest of the smears 73.5% of the results reported negative II. The incidence of failure for this procedure is similar to that of hysterectomy with the same therapeutic goal .

  17. Melanoma mouse model implicates metabotropic glutamate signaling in melanocytic neoplasia.

    PubMed

    Pollock, Pamela M; Cohen-Solal, Karine; Sood, Raman; Namkoong, Jin; Martino, Jeffrey J; Koganti, Aruna; Zhu, Hua; Robbins, Christiane; Makalowska, Izabela; Shin, Seung-Shick; Marin, Yari; Roberts, Kathleen G; Yudt, Laura M; Chen, Amy; Cheng, Jun; Incao, Arturo; Pinkett, Heather W; Graham, Christopher L; Dunn, Karen; Crespo-Carbone, Steven M; Mackason, Kerine R; Ryan, Kevin B; Sinsimer, Daniel; Goydos, James; Reuhl, Kenneth R; Eckhaus, Michael; Meltzer, Paul S; Pavan, William J; Trent, Jeffrey M; Chen, Suzie

    2003-05-01

    To gain insight into melanoma pathogenesis, we characterized an insertional mouse mutant, TG3, that is predisposed to develop multiple melanomas. Physical mapping identified multiple tandem insertions of the transgene into intron 3 of Grm1 (encoding metabotropic glutamate receptor 1) with concomitant deletion of 70 kb of intronic sequence. To assess whether this insertional mutagenesis event results in alteration of transcriptional regulation, we analyzed Grm1 and two flanking genes for aberrant expression in melanomas from TG3 mice. We observed aberrant expression of only Grm1. Although we did not detect its expression in normal mouse melanocytes, Grm1 was ectopically expressed in the melanomas from TG3 mice. To confirm the involvement of Grm1 in melanocytic neoplasia, we created an additional transgenic line with Grm1 expression driven by the dopachrome tautomerase promoter. Similar to the original TG3, the Tg(Grm1)EPv line was susceptible to melanoma. In contrast to human melanoma, these transgenic mice had a generalized hyperproliferation of melanocytes with limited transformation to fully malignant metastasis. We detected expression of GRM1 in a number of human melanoma biopsies and cell lines but not in benign nevi and melanocytes. This study provides compelling evidence for the importance of metabotropic glutamate signaling in melanocytic neoplasia.

  18. Association between calcium intake and colorectal neoplasia in Puerto Rican Hispanics

    PubMed Central

    Palacios, Cristina; Lopez, Maritza; Ortiz, Ana Patricia; Correa, Marcia Cruz

    2017-01-01

    SUMMARY Epidemiological studies show that a high calcium intake reduces the risk of colon cancer. The objective was to study the association between calcium intake and colorectal neoplasia in a clinic-based sample of Hispanics adults from Puerto Rico. As part of this cross-sectional study, a total of 433 subjects were recruited from surgery and gastroenterology clinics at the University of Puerto Rico. Calcium intake was estimated using a food frequency questionnaire (FFQ) of calcium rich foods. Socio-demographics, health history and colonoscopy results were obtained from the primary study. Chi square and odds ratios (OR) for colorectal neoplasia (adenomas and/or adenocarcinoma) were calculated for total calcium, dietary calcium and for calcium supplement use. In total, 312 (72%) from 433 participants completed the FFQ and had available colonoscopy results; from these, 196 (62.5%) were free of neoplasia and 117 (37.5%) had colorectal neoplasia. Colorectal neoplasia subjects were older, a lower proportion were females and less educated than those without neoplasia (p<0.01). Total calcium intake (median 1180 mg/d) was greater in those free of neoplasia compared to colorectal neoplasia subjects (median 1036 mg/d; p<0.05). A high total calcium intake and the use of calcium supplements significantly reduced the OR (crude and age adjusted) for colorectal neoplasia; although these associations lost statistical significance after additionally adjusting for gender and educational level. In conclusion, a high calcium intake and the use of calcium supplements may be protective against colorectal neoplasia, although a greater sample may be required to observe significant associations in a multivariate model. PMID:21866684

  19. Quantitative attenuation analysis for identification of early Barrett's neoplasia in volumetric laser endomicroscopy.

    PubMed

    Swager, Anne-Fre; Faber, Dirk J; de Bruin, Daniel M; Weusten, Bas L; Meijer, Sybren L; Bergman, Jacques J; Curvers, Wouter L; van Leeuwen, Ton G

    2017-08-01

    Early neoplasia in Barrett’s esophagus (BE) is difficult to detect. Volumetric laser endomicroscopy (VLE) incorporates optical coherence tomography, providing a circumferential scan of the esophageal wall layers. The attenuation coefficient (μVLE) quantifies decay of detected backscattered light versus depth, and could potentially improve BE neoplasia detection. The aim is to investigate feasibility of μVLE for identification of early BE neoplasia. In vivo and ex vivo VLE scans with histological correlation from BE patients ± neoplasia were used. Quantification by μVLE was performed manually on areas of interest (AoIs) to differentiate neoplasia from nondysplastic (ND)BE. From ex vivo VLE scans from 16 patients (13 with neoplasia), 68 AoIs were analyzed. Median μVLE values (mm−1) were 3.7 [2.1 to 4.4 interquartile range (IQR)] for NDBE and 4.0 (2.5 to 4.9 IQR) for neoplasia, not statistically different (p=0.82). Fourteen in vivo scans were used: nine from neoplastic and five from NDBE patients. Median μVLE values were 1.8 (1.5 to 2.6 IQR) for NDBE and 2.1 (1.9 to 2.6 IQR) for neoplasia, with no statistically significant difference (p=0.37). In conclusion, there was no significant difference in μVLE values in VLE scans from early neoplasia versus NDBE. Future studies with a larger sample size should explore other quantitative methods for detection of neoplasia during BE surveillance.

  20. Quantitative attenuation analysis for identification of early Barrett's neoplasia in volumetric laser endomicroscopy

    NASA Astrophysics Data System (ADS)

    Swager, Anne-Fre; Faber, Dirk J.; de Bruin, Daniel M.; Weusten, Bas L.; Meijer, Sybren L.; Bergman, Jacques J.; Curvers, Wouter L.; van Leeuwen, Ton G.

    2017-08-01

    Early neoplasia in Barrett's esophagus (BE) is difficult to detect. Volumetric laser endomicroscopy (VLE) incorporates optical coherence tomography, providing a circumferential scan of the esophageal wall layers. The attenuation coefficient (μVLE) quantifies decay of detected backscattered light versus depth, and could potentially improve BE neoplasia detection. The aim is to investigate feasibility of μVLE for identification of early BE neoplasia. In vivo and ex vivo VLE scans with histological correlation from BE patients ± neoplasia were used. Quantification by μVLE was performed manually on areas of interest (AoIs) to differentiate neoplasia from nondysplastic (ND)BE. From ex vivo VLE scans from 16 patients (13 with neoplasia), 68 AoIs were analyzed. Median μVLE values (mm-1) were 3.7 [2.1 to 4.4 interquartile range (IQR)] for NDBE and 4.0 (2.5 to 4.9 IQR) for neoplasia, not statistically different (p=0.82). Fourteen in vivo scans were used: nine from neoplastic and five from NDBE patients. Median μVLE values were 1.8 (1.5 to 2.6 IQR) for NDBE and 2.1 (1.9 to 2.6 IQR) for neoplasia, with no statistically significant difference (p=0.37). In conclusion, there was no significant difference in μVLE values in VLE scans from early neoplasia versus NDBE. Future studies with a larger sample size should explore other quantitative methods for detection of neoplasia during BE surveillance.

  1. 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.

  2. Normal morphogenesis of epithelial tissues and progression of epithelial tumors

    PubMed Central

    Wang, Chun-Chao; Jamal, Leen; Janes, Kevin A.

    2011-01-01

    Epithelial cells organize into various tissue architectures that largely maintain their structure throughout the life of an organism. For decades, the morphogenesis of epithelial tissues has fascinated scientists at the interface of cell, developmental, and molecular biology. Systems biology offers ways to combine knowledge from these disciplines by building integrative models that are quantitative and predictive. Can such models be useful for gaining a deeper understanding of epithelial morphogenesis? Here, we take inventory of some recurring themes in epithelial morphogenesis that systems approaches could strive to capture. Predictive understanding of morphogenesis at the systems level would prove especially valuable for diseases such as cancer, where epithelial tissue architecture is profoundly disrupted. PMID:21898857

  3. Normal morphogenesis of epithelial tissues and progression of epithelial tumors.

    PubMed

    Wang, Chun-Chao; Jamal, Leen; Janes, Kevin A

    2012-01-01

    Epithelial cells organize into various tissue architectures that largely maintain their structure throughout the life of an organism. For decades, the morphogenesis of epithelial tissues has fascinated scientists at the interface of cell, developmental, and molecular biology. Systems biology offers ways to combine knowledge from these disciplines by building integrative models that are quantitative and predictive. Can such models be useful for gaining a deeper understanding of epithelial morphogenesis? Here, we take inventory of some recurring themes in epithelial morphogenesis that systems approaches could strive to capture. Predictive understanding of morphogenesis at the systems level would prove especially valuable for diseases such as cancer, where epithelial tissue architecture is profoundly disrupted.

  4. 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

  5. [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

  6. 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.

  7. Epidemiology of cervical intraepithelial neoplasia: the role of human papillomavirus.

    PubMed

    Cox, J T

    1995-03-01

    The evidence implicating specific HPV types in the aetiology of cervical cancer is now strong enough to establish a causative role. HPV infection of the cervix affects the developing immature metaplastic cells of the transformation zone. Cervical neoplasia can be viewed as the interaction of high risk papillomavirus and immature metaplastic epithelium. Once maturity is reached, there is minimal risk of subsequent development of cervical squamous neoplasia. Exposure to HPV is an extremely common event, especially in young sexually active women. Yet, despite frequent HPV exposure at that phase of life in which the cervical transformation zone is at its most vulnerable, established expressed disease is relatively uncommon. Most studies in which the natural history of CIN is not altered by cervical biopsy reveal a progression rate from low to high grade CIN of less than one third. Where viral type is taken into account, however, the progression rate from normal but high risk HPV-infected cervical epithelium to CIN 2 or 3 is higher. Despite this, most cervical abnormalities will not transform into invasive cancer, even if left untreated. The variance between the high rate of HPV infection, the intermediate rate of CIN and the relatively low rate of cervical cancer establishes a stepwise gradient of disease of increasing severity with decreasing prevalence. In an immunocompetent host, HPV infection alone does not appear to be sufficient to induce the step from high grade CIN to invasion. Epidemiological studies indicating that HPV infection with oncogenic viral types is far more common than cervical neoplasia suggest the necessity of cofactors in cervical carcinogenesis. The long time-lag between initial infection and eventual malignant conversion suggests that random events may be necessary for such conversion, and the spontaneous regression of many primary lesions suggests that most patients are not exposed to these random events. Potential cofactors include cigarette

  8. Male pattern baldness and risk of colorectal neoplasia

    PubMed Central

    Keum, N; Cao, Y; Lee, D H; Park, S M; Rosner, B; Fuchs, C S; Wu, K; Giovannucci, E L

    2016-01-01

    Background: Male pattern baldness is positively associated with androgens as well as insulin-like growth factor 1 (IGF-1) and insulin, all of which are implicated in pathogenesis of colorectal neoplasia. Methods: From 1992 through 2010, we prospectively followed participants in the Health Professionals Follow-Up Study. Hair pattern at age 45 years was assessed at baseline with five image categories (no baldness, frontal-only baldness, frontal-plus-mild-vertex baldness, frontal-plus-moderate-vertex baldness, and frontal-plus-severe-vertex baldness). Cancer analysis included 32 782 men and used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Restricted to men who underwent at least one endoscopy over the study period, adenoma analysis included 29 770 men and used logistic regressions for clustered data to estimate odds ratios (ORs) and 95% CIs. Results: Over the mean follow-up of 15.6 years, 710 cases of colorectal cancer (478 for colon, 152 for rectum, and 80 unknown site) developed. Significantly increased risks associated with frontal-only baldness and frontal-plus-mild-vertex baldness relative to no baldness were observed for colon cancer with respective HR being 1.29 (95% CI, 1.03–1.62) and 1.31 (95% CI, 1.01–1.70). Over the 19-year study period, 3526 cases of colorectal adenoma were detected. Evidence for an increased risk of colorectal adenoma relative to no baldness was significant with frontal-only baldness (OR, 1.16; 95% CI, 1.06–1.26) and borderline insignificant with frontal-plus-severe-vertex baldness (OR, 1.14; 95% CI, 0.98–1.33). Conclusions: Subtypes of male pattern baldness at age 45 years were positively associated with colorectal neoplasia. Future studies are warranted to confirm our results and to determine the predictive value of male pattern baldness to identify those at high risk for colorectal neoplasia. PMID:26757425

  9. Surgical interventions for high grade vulval intraepithelial neoplasia

    PubMed Central

    Kaushik, Sonali; Pepas, Litha; Nordin, Andy; Bryant, Andrew; Dickinson, Heather O

    2014-01-01

    Background Vulval intraepithelial neoplasia (VIN) is a pre-malignant condition of the vulval skin. This uncommon chronic skin condition of the vulva is associated with a high risk of recurrence and the potential to progress to vulval cancer. The condition is complicated by its’ multicentric and multifocal nature. The incidence of this condition appears to be rising particularly in the younger age group. There is a lack of consensus on the optimal surgical treatment method. However, the rationale for surgical treatment of VIN has been to treat symptoms and exclude underlying malignancy with the continued aim of preservation of vulval anatomy and function. Repeated treatments affect local cosmesis and cause psychosexual morbidity thus impacting on the patients’ quality of life. Objectives To evaluate the effectiveness and safety of surgical interventions for high grade VIN. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL), Issue 3, 2010, Cochrane Gynaecological Cancer Group Trials Register, MEDLINE and EMBASE up to September 2010. We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. Selection criteria Randomised controlled trials (RCTs) that compared surgical interventions, in adult women diagnosed with high grade vulval intraepithelial neoplasia. Data collection and analysis Two review authors independently abstracted data and assessed risk of bias. Main results We found only one RCT which included 30 women that met our inclusion criteria and this trial reported data on carbon dioxide laser (CO2 laser) versus ultrasonic surgical aspiration (USA). There was no statistically significant difference in the risk of disease recurrence after one year follow-up, pain, presence of scarring, dysuria or burning, adhesions, infection, abnormal discharge and eschar between women who received CO2 laser and those who received USA. The trial

  10. Polarity in Mammalian Epithelial Morphogenesis

    PubMed Central

    Roignot, Julie; Peng, Xiao; Mostov, Keith

    2013-01-01

    Cell polarity is fundamental for the architecture and function of epithelial tissues. Epithelial polarization requires the intervention of several fundamental cell processes, whose integration in space and time is only starting to be elucidated. To understand what governs the building of epithelial tissues during development, it is essential to consider the polarization process in the context of the whole tissue. To this end, the development of three-dimensional organotypic cell culture models has brought new insights into the mechanisms underlying the establishment and maintenance of higher-order epithelial tissue architecture, and in the dynamic remodeling of cell polarity that often occurs during development of epithelial organs. Here we discuss some important aspects of mammalian epithelial morphogenesis, from the establishment of cell polarity to epithelial tissue generation. PMID:23378592

  11. 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.

  12. CpG Island Methylator Phenotype-High Colorectal Cancers and Their Prognostic Implications and Relationships with the Serrated Neoplasia Pathway

    PubMed Central

    Rhee, Ye-Young; Kim, Kyung-Ju; Kang, Gyeong Hoon

    2017-01-01

    The concept of a CpG island methylator phenotype (CIMP) was first introduced by Toyota and Issa to describe a subset of colorectal cancers (CRCs) with concurrent hypermethylation of multiple CpG island loci. The concept of CIMP as a molecular carcinogenesis mechanism was consolidated by the identification of the serrated neoplasia pathway, in which CIMP participates in the initiation and progression of serrated adenomas. Distinct clinicopathological and molecular features of CIMP-high (CIMP-H) CRCs have been characterized, including proximal colon location, older age of onset, female preponderance, and frequent associations of high-level microsatellite instability and BRAF mutations. CIMP-H CRCs arise in sessile or traditional serrated adenomas and thus tend to display the morphological characteristics of serrated adenomas, including epithelial serration, vesicular nuclei, and abundant cytoplasm. Both the frequent association of CIMP and poor prognosis and different responses of CRCs to adjuvant therapy depending on CIMP status indicate clinical implications. In this review, we present an overview of the literature documenting the relevant findings of CIMP-H CRCs and their relationships with the serrated neoplasia pathway. PMID:27885175

  13. Epithelial infectious crystalline keratopathy.

    PubMed

    Sridhar, M S; Sharma, S; Garg, P; Rao, G N

    2001-02-01

    To report 2 cases of epithelial infectious crystalline keratopathy. Two patients (2 eyes) with significant meibomitis presented with minimal inflammation and plaque-like lesions on the corneal surface made of fine crystalline structures. Corneal scrapings of these lesions were performed for microbiological evaluation. The patients were treated with topical ciprofloxacin and artificial tears. Smear examination of the corneal scrapings revealed numerous bacteria and keratinized epithelial cells with no inflammatory cells. Culture showed a significant growth of Staphylococcus epidermidis and Corynebacterium species in the first case and Pseudomonas aeroginosa in the second case. The response to treatment was poor, with recurrence of the crystalline lesion. Infectious crystalline keratopathy lesions may involve the epithelium and occur on the corneal surface.

  14. [Currently available classifications of lymphoid neoplasia and their clinical applicability].

    PubMed

    Nakamine, H; Nanba, K

    1996-11-01

    Controversy and confusion in the classification of lymphoid neoplasia have long been sources of frustration as exemplifed by the statement of Rupert A. Willis in 1948, that "Nowhere in pathology has a chaos of names so clouded clear concept as in the subject of lymphoid tumors." Taxonomically, "Classifications are theories about the basis of natural order, not dull catalogues compiled only to avoid chaos." (Stephen J. Gould, 1989), but this definition can not always be applicable to the classifications of human diseases, even though they themselves are also biologic phenomena. The International Lymphoma Study Group has recently proposed "a revised European-American classification of lymphoid neoplasms", which has again resulted in the time of "the great debate". The major purpose of this article is, therefore, to assess the above classification.

  15. 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.

  16. The microcolposcopy in the management of the cervical intraepithelial neoplasia.

    PubMed

    Mencaglia, L; Branconi, F; Scarselli, G; Locatelli, F; Savino, L; Chelo, E; Marchionni, M

    1983-01-01

    The authors report their experience with the microcolpohysteroscope of Hamou. This instrument allows a magnification from 0 to 150 times. Its fine caliber (4 mm) allows to work easily also in the interior of the cervical canal, without preventive dilatation. The instrument allows the in vivo vision of the cellular arrangement at the superficial level, after vital staining. The purpose of this research is the discussion of the potentiality of the microcolpohysteroscopy as complementary mean to colposcopy, citology and histology in the management of the Cervical Intraepithelial Neoplasia (CIN). The authors conclude showing the advantages of this technique underlining as this method does not interfere with the natural evolution of the pathologic process, allowing at the contrary to determine the nature and the extension of the lesion. Then, without opposing or to citology or to colposcopy or to histology, it is not only a valid complementary diagnostic mean, but in particularly it contributes to a more rational therapeutic decision.

  17. Gastroenteropancreatic Neuroendocrine Tumors in Multiple Endocrine Neoplasia Type 1

    PubMed Central

    Tonelli, Francesco; Giudici, Francesco; Giusti, Francesca; Brandi, Maria Luisa

    2012-01-01

    We reviewed the literature about entero-pancreatic neuroendocrine tumors in Multiple Endocrine Neoplasia type 1 syndrome (MEN1) to clarify their demographic features, localization imaging, practice, and appropriate therapeutical strategies, analyzing the current approach to entero-pancreatic neuroendocrine tumors in MEN1. Despite the fact that hyperparathyroidism is usually the first manifestation of MEN1, the penetrance of these tumors is similar. They are characterized by multiplicity of lesions, variable expression of the tumors, and propensity for malignant degeneration. Both the histological type and the size of MEN1 neuroendocrine tumors correlate with malignancy. Monitoring of pancreatic peptides and use of imaging exams allow early diagnosis and prompt surgical treatment, resulting in prevention of metastatic disease and improvement of long-term survival. Surgery is often the treatment of choice for MEN1-neuroendocrine tumors. The rationale for surgical approach is to curtail malignant progression of the disease, and to cure the associated biochemical syndrome, should it be present. PMID:24213321

  18. 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.

  19. Myeloid neoplasias: what molecular analyses are telling us.

    PubMed

    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.

  20. 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

  1. Preconception radiation, intrauterine diagnostic radiation, and childhood neoplasia

    SciTech Connect

    Shiono, P.H.; Chung, C.S.; Myrianthopoulos, N.C.

    1980-10-01

    Diagnostic x-ray examinations as a potential risk for neoplasia were investigated in a prospective study of 55,908 women who participated in the Collaborative Perinatal Project of the National Institute of Neurological and Communicative Disorders and Stroke. The x-ray exposure histories of 145 mothers whose children developed neoplasms and 290 matched controls were examined. Of the childhood neoplasms, 40 were malignant and 105 were benign. Generally, the data were consistent with increased risk of malignant neoplasms among children of women exposed to x-rays before and during pregnancy, with a somewhat higher relative risk estimate for preconception exposure. No significant association of x-ray exposure and benign neoplasms was detected.

  2. 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

  3. A metastatic ovarian angiosarcoma mimicking hematologic neoplasia at diagnosis.

    PubMed

    Gaiolla, Rafael Dezen; Duarte, Ivison 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.

  4. 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

  5. Multiple endocrine neoplasia type IIb: a case report.

    PubMed

    Jaruratanasirikul, S; Patarakijvanich, N; Patrapinyokul, S; Saetung, P

    1993-06-01

    We reported a 14-year-old boy who had had multiple thyroid nodules for 4 yrs. Physical examination revealed marfanoid habitus, coarse facies with thick lips and prominent jaw. Mucosal neuromas were present on the buccal mucosa, tongue and upper eyelids. Thyroid scan demonstrated multiple, cold nodules and medullary thyroid carcinoma was confirmed by pathological examination. He was normotensive and his 24 hrs urinary vanillyl mandelic acid was in the normal range. Computerized tomography demonstrated normal adrenal glands. Multiple endocrine neoplasia type IIb (MEN IIb) was diagnosed by the appearance of typical phenotypic features, multiple mucosal neuromas and medullary thyroid carcinoma. The scarcity of such reports in children and the importance of early recognition of this disorder prompted us to describe this patient.

  6. Current Chemotherapeutic Management of Patients with Gestational Trophoblastic Neoplasia

    PubMed Central

    May, Taymaa; Goldstein, Donald P.; Berkowitz, Ross S.

    2011-01-01

    Gestational trophoblastic neoplasia (GTN) describes a heterogeneous group of interrelated lesions that arise from abnormal proliferation of placental trophoblasts. GTN lesions are histologically distinct, malignant lesions that include invasive hydatidiform mole, choriocarcinoma, placental site trophoblastic tumor (PSTT) and epithelioid trophoblastic tumor (ETT). GTN tumors are generally highly responsive to chemotherapy. Early stage GTN disease is often cured with single-agent chemotherapy. In contrast, advanced stage disease requires multiagent combination chemotherapeutic regimens to achieve a cure. Various adjuvant surgical procedures can be helpful to treat women with GTN. Patients require careful followup after completing treatment and recurrent disease should be aggressively managed. Women with a history of GTN are at increased risk of subsequent GTN, hence future pregnancies require careful monitoring to ensure normal gestational development. This article will review the workup, management and followup of women with all stages of GTN as well as with recurrent disease. PMID:22312558

  7. The spectrum of plasma cell neoplasia in oral pathology.

    PubMed

    Seoane, Juan; Aguirre-Urizar, José Manuel; Esparza-Gómez, Germán; Suárez-Cunqueiro, Mercedes; Campos-Trapero, Julián; Pomareda, Manuel

    2003-01-01

    Plasma cell tumors are lymphoid neoplastic proliferations of B cells that may be classified as multiple myeloma (MM), solitary bone plasmacytoma (SBP) and extramedullary plasmacytoma (PEM). These types of neoplasia are typically found in adults and may occur as disseminated tumors of the bone marrow or in some cases as solitary bone or extramedullary tumors. Most SBP eventually develop into MM, whereas only 30% of the PEM do so. Oral manifestations in the form of oral and maxillofacial lesions are often the first sign of the disease. Treatment of these neoplastic tumors varies depending on the type of proliferation and may involve surgery, radiotherapy and chemotherapy, alone or combined. This paper reviews the main clinical and pathological aspects of these tumors and their relationship to the oral and maxillofacial area.

  8. Uterine cervical neoplasia prevention in Parque Indigena do Xingu.

    PubMed

    Speck, N M de Góis; Pereira, E R; Schaper, M; Tso, F K; de Freitas, V G; Ribalta, J C L

    2009-01-01

    Results of preventive health measures, diagnosis and treatment applied to Parque Indigena do Xingu native women were studied. Thirty-seven cases of uterine cervical intraepithelial lesions and invasive neoplasias were treated in the local villages without referral to an advanced medical center. LEEPs were carried out in 32 women, three cold knife conizations, one vaginal hysterectomy and one Wertheim Meigs procedure. Results of 53.1% of LEEP surgical procedures did not have margin involvement by the lesions. Bleeding complications were seen in 15.6%. Regular follow-up with two or three cytologic and colposcopic tests in 32 women was carried out. All cases were negative for lesions. Five women were not followed-up due mainly to logistical reasons. Health endeavors adopted in the period 2005-2007 brought about a significant reduction of precursor lesions in this native aboriginal population without screening resources.

  9. Is There a Relationship between Ovarian Epithelial Dysplasia and Infertility?

    PubMed

    Chene, Gautier; Penault-Llorca, Frédérique; Tardieu, Anne; Cayre, Anne; Lagarde, Nicole; Jaffeux, Patricia; Aublet-Cuvelier, Bruno; Dechelotte, Pierre; Felloni, Bertrand; Pouly, Jean-Luc; Dauplat, Jacques

    2012-01-01

    Aim. Ovarian epithelial dysplasia was initially described in material from prophylactic oophorectomies performed in patients at genetic risk of ovarian cancer. Similar histopathological abnormalities have been revealed after ovulation stimulation. Since infertility is also a risk factor for ovarian neoplasia, the aim of this study was to study the relationship between infertility and ovarian dysplasia. Methods. We blindly reviewed 127 histopathological slides of adnexectomies or ovarian cystectomies according to three groups-an exposed group to ovulation induction (n = 30), an infertile group without stimulation (n = 35), and a spontaneously fertile control group (n = 62)-in order to design an eleven histopathological criteria scoring system. Results. The ovarian dysplasia score was significantly higher in exposed group whereas dysplasia score was low in infertile and control groups (resp., 8.21 in exposed group, 3.69 for infertile patients, and 3.62 for the controls). In the subgroup with refractory infertility there was a trend towards a more severe dysplasia score (8.53 in ovulation induction group and 5.1 in infertile group). Conclusion. These results raise questions as to the responsibility of drugs used to induce ovulation and/or infertility itself in the genesis of ovarian epithelial dysplasia.

  10. Cutis rhomboidalis protects skin from malignant epithelial tumors.

    PubMed

    Bonkevitch, F; Souza, P R M

    2014-06-01

    Cutis rhomboidalis nuchae is a skin alteration which comes from chronic sun exposure and it integrates the solar elastosis group, acquiring a coriaceous aspect, with a yellowish and grooved surface. There is the occurrence of elastic and collagen fibers degeneration found in the dermis caused by ultraviolet radiation [1]. Another group of skin diseases which has solar exposure as a determining factor is the group of actinic keratoses, the non-melanoma malignant epithelial tumors {basal cell carcinoma (CBC) and squamous cell carcinoma (CEC)} [2]. However, the occurrence of actinic keratoses, CBCs or CECs on the area of cutis rhomboidalis is infrequent in dermatology clinical practice. The authors do not know why people with neoplasias and pre neoplastic lesions in some areas with chronic photo damage amendments (face and upper limbs), do not present the same pre and neoplastic lesions in areas with similar appearance of chronic sun damage (nape). The authors seek to understand why the nape is protected for pre and neoplastic lesions. We suggest that cutis rhomboidalis protects skin from malignant epithelial tumors in nuchae.

  11. Epithelial adhesive junctions

    PubMed Central

    Capaldo, Christopher T.; Farkas, Attila E.

    2014-01-01

    Epithelial adhesive cell-to-cell contacts contain large, plasma membrane-spanning multiprotein aggregates that perform vital structural and signaling functions. Three prominent adhesive contacts are the tight junction, adherens junction, and the desmosome. Each junction type has unique cellular functions and a complex molecular composition. In this review, we comment on recent and exciting advances in our understanding of junction composition and function. PMID:24592313

  12. 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.

  13. Predictive cytogenetic biomarkers for colorectal neoplasia in medium risk patients

    PubMed Central

    Ionescu, EM; Nicolaie, T; Ionescu, MA; Becheanu, G; Andrei, F; Diculescu, M; Ciocirlan, M

    2015-01-01

    Rationale: DNA damage and chromosomal alterations in peripheral lymphocytes parallels DNA mutations in tumor tissues. Objective: The aim of our study was to predict the presence of neoplastic colorectal lesions by specific biomarkers in “medium risk” individuals (age 50 to 75, with no personal or family of any colorectal neoplasia). Methods and Results: We designed a prospective cohort observational study including patients undergoing diagnostic or opportunistic screening colonoscopy. Specific biomarkers were analyzed for each patient in peripheral lymphocytes - presence of micronuclei (MN), nucleoplasmic bridges (NPB) and the Nuclear Division Index (NDI) by the cytokinesis-blocked micronucleus assay (CBMN). Of 98 patients included, 57 were “medium risk” individuals. MN frequency and NPB presence were not significantly different in patients with neoplastic lesions compared to controls. In “medium risk” individuals, mean NDI was significantly lower for patients with any neoplastic lesions (adenomas and adenocarcinomas, AUROC 0.668, p 00.5), for patients with advanced neoplasia (advanced adenoma and adenocarcinoma, AUROC 0.636 p 0.029) as well as for patients with adenocarcinoma (AUROC 0.650, p 0.048), for each comparison with the rest of the population. For a cut-off of 1.8, in “medium risk” individuals, an NDI inferior to that value may predict any neoplastic lesion with a sensitivity of 97.7%, an advanced neoplastic lesion with a sensitivity of 97% and adenocarcinoma with a sensitivity of 94.4%. Discussion: NDI score may have a role as a colorectal cancer-screening test in “medium risk” individuals. Abbreviations: DNA = deoxyribonucleic acid; CRC = colorectal cancer; EU = European Union; WHO = World Health Organization; FOBT = fecal occult blood test; CBMN = cytokinesis-blocked micronucleus assay; MN = micronuclei; NPB = nucleoplasmic bridges; NDI = Nuclear Division Index; FAP = familial adenomatous polyposis; HNPCC = hereditary non

  14. Serrated polyposis: rapid and relentless development of colorectal neoplasia.

    PubMed

    Edelstein, Daniel L; Axilbund, Jennifer E; Hylind, Linda M; Romans, Katharine; Griffin, Constance A; Cruz-Correa, Marcia; Giardiello, Francis M

    2013-03-01

    Serrated (hyperplastic) polyposis (SP) is a rare disorder with multiple colorectal hyperplastic polyps and often sessile serrated adenomas/polyps (SSA/P) or adenomas. Although associated with colorectal cancer, the course of SP is not well described. 44 patients with SP were studied. The results of 146 colonoscopies with median follow-up of 2.0 years (range 0-30) and a median of 1.0 years (range 0.5-6) between surveillance colonoscopies were evaluated. Findings from oesophogastroduodenoscopy examinations were analysed. The mean age at diagnosis of SP was 52.5 ± 11.9 years (range 22-78). In two pedigrees (5%) another family member had SP. None of 22 patients had gastroduodenal polyps. All patients had additional colorectal polyps at surveillance colonoscopy. SSA/P or adenomas were found in 25 patients (61%) at first colonoscopy and 83% at last colonoscopy. Recurrent SSA/P or adenomas occurred in 68% of patients at surveillance colonoscopy. Three patients had colorectal cancer. Eleven patients (25%) underwent surgery (mean time from diagnosis of SP 2.0 ± 0.9 years). After surgery all seven surveyed patients developed recurrent polyps in the retained colorectum (4/7 had SSA/P or adenomas). No association was found between colorectal neoplasia and sex, age at diagnosis of SP or initial number of colorectal polyps. In SP, rapid and unrelenting colorectal neoplasia development continues in the intact colorectum and retained segment after surgery. These findings support the possibility of annual colonoscopic surveillance, consideration for colectomy when SSA/P or adenomas are encountered and frequent postoperative endoscopic surveillance of the retained colorectum.

  15. Viral-type orchitis: a potential mimic of testicular neoplasia.

    PubMed

    Braaten, Kristina M; Young, Robert H; Ferry, Judith A

    2009-10-01

    Orchitis of viral or presumed viral etiology is an uncommon cause of testicular pain or enlargement. Rarely orchitis is clinically or radiographically suggestive of neoplasia, resulting in a testicular biopsy or orchiectomy being performed. Between 1978 and 2004, 10 cases submitted in consultation were diagnosed as orchitis at the Massachusetts General Hospital. The patients were from 18 to 37 years of age and presented with testicular enlargement or a mass, pain, or both. Radiographic studies were suspicious for a neoplasm in all 5 cases in which results were available. The patients underwent testicular biopsy (2 cases), orchiectomy (6 cases), biopsy immediately followed by orchiectomy (1 case), or biopsy followed by orchiectomy 3 weeks later (1 case). The cases were submitted with diagnoses that included intratubular seminoma, intratubular germ cell neoplasia, unspecified, Sertoli cell hyperplasia, myeloid sarcoma, and lymphoma. Microscopic examination revealed preservation of the architecture of the testicular parenchyma, typically with hemorrhage and edema, with patchy inflammation in the form of a lymphohistiocytic infiltrate within seminiferous tubules and also between tubules. The intratubular infiltrate usually predominated. Immunohistochemical studies, performed in 7 cases showed a mixture of CD68+ histiocytes and CD3+ T cells, with few B cells (CD20+) and few granulocytes. Follow-up was available in 5 cases; all 5 patients were alive and well 11 months to 10 years after diagnosis. In the rare instance in which a testicular specimen with orchitis is submitted for pathologic evaluation, diagnosis may be difficult. Familiarity with the pathologic changes characteristic of orchitis will help avoid misdiagnosis.

  16. Computed tomographic findings in 57 cats with primary pulmonary neoplasia.

    PubMed

    Aarsvold, Stacie; Reetz, Jennifer A; Reichle, Jean K; Jones, Ian D; Lamb, Christopher R; Evola, Maria G; Keyerleber, Michele A; Marolf, Angela J

    2015-01-01

    Primary pulmonary neoplasia is relatively uncommon in cats and generally has a poor prognosis. In this multicenter, retrospective study of 57 cats with pulmonary neoplasia, the most frequent presenting signs were anorexia/inappetence (39%) and cough (37%). The pulmonary tumors were considered to be incidental findings in 9% cats. In computed tomographic (CT) images, primary pulmonary tumors appeared as a pulmonary mass in 55 (96%) cats and as a disseminated pulmonary lesion without a defined mass in two (4%) cats. Most pulmonary tumors were in the caudal lobes, with 28 (49%) in the right caudal lobe and 17 (30%) in the left caudal lobe. CT features associated with pulmonary tumors included mass in contact with visceral pleura (96%), irregular margins (83%), well-defined borders (79%), bronchial compression (74%), gas-containing cavities (63%), foci of mineral attenuation (56%), and bronchial invasion (19%). The mean (range) maximal dimension of the pulmonary masses was 3.5 cm (1.1-11.5 cm). Additional foci of pulmonary disease compatible with metastasis were observed in 53% cats. Pleural fluid was evident in 30% cats and pulmonary thrombosis in 12% cats. The histologic diagnoses were 47 (82%) adenocarcinomas, six (11%) tumors of bronchial origin, three (5%) adenosquamous cell carcinomas, and one (2%) squamous cell carcinoma. In this series, adenocarcinoma was the predominant tumor type, but shared many features with less common tumor types. No associations were identified between tumor type and CT features. Prevalence of suspected intrapulmonary metastasis was higher than in previous radiographic studies of cats with lung tumors.

  17. 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

  18. Successful treatment of recurrent vulvar intraepithelial neoplasia resistant to interferon and isotretinoin with cidofovir.

    PubMed

    Koonsaeng, S; Verschraegen, C; Freedman, R; Bossens, M; Kudelka, A; Kavanagh, J; Sittisomwong, T; DeClercq, E; Snoeck, R

    2001-06-01

    Vulvar intraepithelial neoplasias are difficult to eradicate completely without extensive surgical intervention. Cidofovir, a deoxycytidine monophosphate analog, may have a therapeutic role in this disease. A 43-year-old woman with a 20-year history of genital warts presented with extensive vulvar intraepithelial neoplasia III, and refused surgical resection. Topical cidofovir 1% in Beeler base completely eradicated the lesion. Successive treatment applications, however, were necessary. Cidofovir is a promising topical antiviral compound for HPV induced vulvar intraepithelial neoplasia. Copyright 2001 Wiley-Liss, Inc.

  19. 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

  20. Morphologic and molecular evolutionary pathways of low nuclear grade invasive breast cancers and their putative precursor lesions: further evidence to support the concept of low nuclear grade breast neoplasia family.

    PubMed

    Abdel-Fatah, Tarek M A; Powe, Desmond G; Hodi, Zsolt; Reis-Filho, Jorge S; Lee, Andrew H S; Ellis, Ian O

    2008-04-01

    We have previously provided evidence showing an association between some precursor lesions with low nuclear grade breast carcinomas (LNGBCs). In this study, further immunophenotypic support to our proposed route of pathogenesis of LNGBC and their precursor lesions was provided. Precursor lesions including columnar cell lesions, atypical ductal hyperplasia, ductal carcinoma in situ, usual epithelial hyperplasia, and lobular neoplasia were compared with matching "morphologically normal" terminal lobular duct units and matching invasive carcinoma. The epithelial cells in the putative precursor flat epithelial atypia, atypical ductal hyperplasia, lobular neoplasia, ductal carcinoma in situ lesions, and their coexisting LNGBC were negative for basal and myoepithelial markers, but positive for CK19/18/8, estrogen receptor (ER)-alpha, Bcl-2, and cyclin D1. The ER-alpha/ER-beta expression ratio increased during carcinogenesis, as did expression of cyclin D1 and Bcl-2. p53 immunopositivity was found 3% in LNGBC versus 43% in high nuclear grade breast carcinoma (HNGBC), whereas ataxia telangiectasia mutated expression was absent or reduced in 22% of LNGBC versus 53% of HNGBC cases. In summary, our findings support the concept that flat epithelial atypia is the earliest morphologically identifiable nonobligate precursor lesion of LNGBC. These may represent a family of precursor, in situ and invasive neoplastic lesions belonging to the luminal "A" subclass of breast cancer. The balance between ER-alpha and ER-beta expression may be important in driving cyclin D-1 and Bcl-2 expression. Ataxia telangiectasia mutated may be one of the alternative regulatory mechanisms to TP53 mutation or dysfunction in low-grade and high-grade breast carcinoma. Our findings support the concept that progression of LNGBC to HNGBC (basal-like or HER2+) phenotype is an unlikely biologic phenomenon.

  1. HPV-16 in a distinct subset of oral epithelial dysplasia.

    PubMed

    Lerman, Mark A; Almazrooa, Soulafa; Lindeman, Neal; Hall, Dimity; Villa, Alessandro; Woo, Sook-Bin

    2017-08-11

    Human papillomavirus (HPV) 16 is the most common high-risk HPV type identified in oropharyngeal and cervical neoplasia. Recently, HPV-associated oral epithelial dysplasia with specific histopathologic features and demographics similar to HPV-oropharyngeal carcinoma has been identified. The objective of this study was to evaluate histopathologically all cases of HPV-oral epithelial dysplasia seen in one center and identify HPV types in a subset of cases. Cases with specific histopathology for HPV-oral epithelial dysplasia that were positive both by immunohistochemical studies for p16 and by in situ hybridization for high-risk types of HPV were further analyzed using QIAamp DNA Tissue Kits (Qiagen, Hilden, Germany). DNA was extracted, amplified, and digested with restriction enzymes and run on a polyacrylamide gel. Digestion patterns were visually compared with a database of known HPV digestion patterns for identification. There were 53 specimens included in the analysis. There were 47 males and six females (7.8:1), with a median age of 55 years (range 41-81). The most common site of involvement was the tongue/floor of mouth (77% of cases). Of the 53 cases, 94% exhibited parakeratosis and/or hyperkeratosis. All the cases featured karyorrhexis, apoptosis, and characteristics of conventional carcinoma in situ. The quantity of DNA extracted was sufficient for analysis in 22 cases. HPV-16 was identified in 20/22 (91%) cases. One case was associated with HPV-33 and one with HPV-58 (5% each). Eight of the 53 cases (15%) were associated with invasive squamous cell carcinomas.Modern Pathology advance online publication, 11 August 2017; doi:10.1038/modpathol.2017.71.

  2. The effect of distance traveled on disease outcomes in gestational trophoblastic neoplasia.

    PubMed

    Clark, Leslie H; Staley, S Allison; Barber, Emma L; Wysham, Weiya Z; Kim, Kenneth H; Soper, John T

    2016-08-01

    Gestational trophoblastic neoplasia is a rare gynecological malignancy often treated at tertiary referral centers. Patients frequently travel long distances to obtain care for gestational trophoblastic neoplasia, which may affect cancer outcomes in these patients. We examined the association between distance traveled to obtain care and disease burden at time of presentation as well as recurrence. We performed a retrospective cohort analysis of all patients diagnosed with gestational trophoblastic neoplasia from January 1995 to June 2015 at a high-volume tertiary referral center. Patients were included if they met International Federation of Gynecology and Obstetrics 2000 criteria for postmolar gestational trophoblastic neoplasia or had choriocarcinoma, placental-site trophoblastic tumor, or epithelioid trophoblastic tumor. Sixty patients were identified. Disease burden at presentation was examined using both the World Health Organization prognostic score and International Federation of Gynecology and Obstetrics. Patients who traveled more than 50 miles were considered long-distance travelers based on previous literature on the effect of distance traveled on cancer outcomes. Demographic, clinical, and pathological data were obtained by chart review. Bivariable comparisons were performed using the χ(2) test or Fisher exact test for categorical variables. The t test or Wilcoxon rank-sum test was used to compare continuous variables when normally or not normally distributed. Most patients presented at stage I (61%) with low-risk gestational trophoblastic neoplasia (70%). Median distance to care was 40 miles (range, 4-384). Eighteen patients (30%) had no insurance and 42 (70%) had either private or public insurance. Patients traveling more than 50 miles for care were more likely to have high-risk gestational trophoblastic neoplasia (46% vs 19%, P = .03), but there was no difference in recurrence (13% vs 11%, P = .89). Patients with high-risk gestational

  3. Neoplasia in Turner syndrome. The importance of clinical and screening practices during follow-up.

    PubMed

    Larizza, Daniela; Albanesi, Michela; De Silvestri, Annalisa; Accordino, Giulia; Brazzelli, Valeria; Maffè, Gabriella Carnevale; Calcaterra, Valeria

    2016-05-01

    Turmer syndrome (TS) patients show increased morbidity due to metabolic, autoimmune and cardiovascular disorders. A risk of neoplasia is also reported. Here, we review the prevalence of neoplasia in a cohort of Turner patients. We retrospectively evaluated 87 TS women. Follow-up included periodic ultrasound of the neck, abdominal and pelvic organs, dermatologic evaluation and fecal occult blood test. Karyotype was 45,X in 46 patients. During follow-up, 63 girls were treated with growth hormone, 65 with estro-progestin replacement therapy and 20 with L-thyroxine. Autoimmune diseases were present in 29 TS. A total of 17 neoplasms in 14 out of 87 patients were found. Six skin neoplasia, 3 central nervous system tumors, 3 gonadal neoplasia, 2 breast tumors, 1 hepatocarcinoma, 1 carcinoma of the pancreas and 1 follicular thyroid cancer were detected. Age at tumor diagnosis was higher in 45,X pts than in those with other karyotypes (p = 0.003). Adenomioma gallbladdder (AG) was detected in 15.3% of the patients, with a lower age in girls at diagnosis with an associated neoplasia in comparison with TS without tumors (p = 0.017). No correlation between genetic make up, treatment, associated autoimmune diseases and neoplastia was found. In our TS population an increased neoplasia prevalence was reported. A high prevalence of AG was also noted and it might be indicative of a predisposition to neoplasia. Further studies are needed to define the overall risk for neoplasia, and to determine the role of the loss of the X-chromosome and hormonal therapies. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  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. High-resolution genomic profiling of human papillomavirus-associated vulval neoplasia

    PubMed Central

    Purdie, K J; Harwood, C A; Gibbon, K; Chaplin, T; Young, B D; Cazier, J B; Singh, N; Leigh, I M; Proby, C M

    2010-01-01

    Background: The incidence of human papillomavirus-associated vulval neoplasia is increasing worldwide; yet the associated genetic changes remain poorly understood. Methods: We have used single-nucleotide polymorphism microarray analysis to perform the first high-resolution investigation of genome-wide allelic imbalance in vulval neoplasia. Our sample series comprised 21 high-grade vulval intraepithelial neoplasia and 6 vulval squamous cell carcinomas, with paired non-lesional samples used to adjust for normal copy number variation. Results: Overall the most common recurrent aberrations were gains at 1p and 20, with the most frequent deletions observed at 2q, 3p and 10. Copy-neutral loss of heterozygosity at 6p was a recurrent event in vulval intraepithelial neoplasia. The pattern of genetic alterations differed from the characteristic changes we previously identified in cutaneous squamous cell carcinomas. Vulval neoplasia samples did not exhibit gain at 5p, a frequent recurrent aberration in a series of cervical tumours analysed elsewhere using an identical protocol. Conclusion: This series of 27 vulval samples comprises the largest systematic genome-wide analysis of vulval neoplasia performed to date. Despite shared papillomavirus status and regional proximity, our data suggest that the frequency of certain genetic alterations may differ in vulval and cervical tumours. PMID:20234371

  6. Prevalence of neoplasia in llamas and alpacas (Oregon State University, 2001-2006).

    PubMed

    Valentine, Beth A; Martin, Jeanne M

    2007-03-01

    Prevalence and type of neoplastic disease were determined in 551 camelid submissions (368 alpacas [Lama pacos], 180 llamas [Lama glama], and 3 cases in which species was not identified) over a 5-year period. Forty neoplasms were identified in 38 animals (6.9%). Prevalence of neoplasia in llamas was higher (11%) than in alpacas (4.9%). Mean age of camelids with neoplasia was 9.42 +/- 4.9 years. Mean age of alpacas with neoplasia (5.48 +/- 3.7 years) was significantly less than of llamas with neoplasia (12.53 +/- 3.2 years; P < 0.001). Cutaneous and mucocutaneous fibroma/fibropapilloma was most common (10 animals), followed by cutaneous and mucocutaneous squamous cell carcinoma (6 animals), disseminated lymphoma (5 animals), and fibrosarcoma (4 animals). Four of 5 animals with lymphoma were alpacas, aged 0.21 to 4 years. Lymphoma occurred in 1 aged llama (15 years). Disseminated carcinoma and adenocarcinoma occurred in 4 llamas and 2 alpacas, and included biliary (2), gastrointestinal (2), mammary gland (1), and unknown (1) origin. Mean age of camelids with any type of carcinoma or adenocarcinoma (12.36 +/- 2.8 years) was significantly greater than that of camelids with lymphoma (4.24 +/- 6.2 years; P = 0.02). Results indicate that neoplasia is relatively common in camelids and that there are differences between llamas and alpacas as regards prevalence of neoplasia, tumor types, and age at diagnosis.

  7. Epithelial cell responses to infection with human papillomavirus.

    PubMed

    Stanley, Margaret A

    2012-04-01

    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 keratinocytes

  8. 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

  9. 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

  10. Drosophila MOF regulates DIAP1 and induces apoptosis in a JNK dependent pathway.

    PubMed

    Pushpavalli, Sreerangam N C V L; Sarkar, Arpita; Ramaiah, M Janaki; Koteswara Rao, G; Bag, Indira; Bhadra, Utpal; Pal-Bhadra, Manika

    2016-03-01

    Histone modulations have been implicated in various cellular and developmental processes where in Drosophila Mof is involved in acetylation of H4K16. Reduction in the size of larval imaginal discs is observed in the null mutants of mof with increased apoptosis. Deficiency involving Hid, Reaper and Grim [H99] alleviated mof (RNAi) induced apoptosis in the eye discs. mof (RNAi) induced apoptosis leads to activation of caspases which is suppressed by over expression of caspase inhibitors like P35 and Diap1 clearly depicting the role of caspases in programmed cell death. Also apoptosis induced by knockdown of mof is rescued by JNK mutants of bsk and tak1 indicating the role of JNK in mof (RNAi) induced apoptosis. The adult eye ablation phenotype produced by ectopic expression of Hid, Rpr and Grim, was restored by over expression of Mof. Accumulation of Mof at the Diap1 promoter 800 bp upstream of the transcription start site in wild type larvae is significantly higher (up to twofolds) compared to mof (1) mutants. This enrichment coincides with modification of histone H4K16Ac indicating an induction of direct transcriptional up regulation of Diap1 by Mof. Based on these results we propose that apoptosis triggered by mof (RNAi) proceeds through a caspase-dependent and JNK mediated pathway.

  11. β1 integrin- and JNK-dependent tumor growth upon hypofractionated radiation.

    PubMed

    Sayeed, Aejaz; Lu, Huimin; Liu, Qin; Deming, David; Duffy, Alexander; McCue, Peter; Dicker, Adam P; Davis, Roger J; Gabrilovich, Dmitry; Rodeck, Ulrich; Altieri, Dario C; Languino, Lucia R

    2016-08-16

    Radiation therapy is an effective cancer treatment modality although tumors invariably become resistant. Using the transgenic adenocarcinoma of mouse prostate (TRAMP) model system, we report that a hypofractionated radiation schedule (10 Gy/day for 5 consecutive days) effectively blocks prostate tumor growth in wild type (β1wt /TRAMP) mice as well as in mice carrying a conditional ablation of β1 integrins in the prostatic epithelium (β1pc-/- /TRAMP). Since JNK is known to be suppressed by β1 integrins and mediates radiation-induced apoptosis, we tested the effect of SP600125, an inhibitor of c-Jun amino-terminal kinase (JNK) in the TRAMP model system. Our results show that SP600125 negates the effect of radiation on tumor growth in β1pc-/- /TRAMP mice and leads to invasive adenocarcinoma. These effects are associated with increased focal adhesion kinase (FAK) expression and phosphorylation in prostate tumors in β1pc-/- /TRAMP mice. In marked contrast, radiation-induced tumor growth suppression, FAK expression and phosphorylation are not altered by SP600125 treatment of β1wt /TRAMP mice. Furthermore, we have reported earlier that abrogation of insulin-like growth factor receptor (IGF-IR) in prostate cancer cells enhances the sensitivity to radiation. Here we further explore the β1/IGF-IR crosstalk and report that β1 integrins promote cell proliferation partly by enhancing the expression of IGF-IR. In conclusion, we demonstrate that β1 integrin-mediated inhibition of JNK signaling modulates tumor growth rate upon hypofractionated radiation.

  12. β1 integrin- and JNK-dependent tumor growth upon hypofractionated radiation

    PubMed Central

    Sayeed, Aejaz; Lu, Huimin; Liu, Qin; II, David Deming; Duffy, Alexander; McCue, Peter; Dicker, Adam P.; Davis, Roger J.; Gabrilovich, Dmitry; Rodeck, Ulrich; Altieri, Dario C.; Languino, Lucia R.

    2016-01-01

    Radiation therapy is an effective cancer treatment modality although tumors invariably become resistant. Using the transgenic adenocarcinoma of mouse prostate (TRAMP) model system, we report that a hypofractionated radiation schedule (10 Gy/day for 5 consecutive days) effectively blocks prostate tumor growth in wild type (β1wt /TRAMP) mice as well as in mice carrying a conditional ablation of β1 integrins in the prostatic epithelium (β1pc-/- /TRAMP). Since JNK is known to be suppressed by β1 integrins and mediates radiation-induced apoptosis, we tested the effect of SP600125, an inhibitor of c-Jun amino-terminal kinase (JNK) in the TRAMP model system. Our results show that SP600125 negates the effect of radiation on tumor growth in β1pc-/- /TRAMP mice and leads to invasive adenocarcinoma. These effects are associated with increased focal adhesion kinase (FAK) expression and phosphorylation in prostate tumors in β1pc-/- /TRAMP mice. In marked contrast, radiation-induced tumor growth suppression, FAK expression and phosphorylation are not altered by SP600125 treatment of β1wt /TRAMP mice. Furthermore, we have reported earlier that abrogation of insulin-like growth factor receptor (IGF-IR) in prostate cancer cells enhances the sensitivity to radiation. Here we further explore the β1/IGF-IR crosstalk and report that β1 integrins promote cell proliferation partly by enhancing the expression of IGF-IR. In conclusion, we demonstrate that β1 integrin-mediated inhibition of JNK signaling modulates tumor growth rate upon hypofractionated radiation. PMID:27438371

  13. NKCC1 Activation Is Required for Myelinated Sensory Neurons Regeneration through JNK-Dependent Pathway.

    PubMed

    Mòdol, Laura; Santos, Daniel; Cobianchi, Stefano; González-Pérez, Francisco; López-Alvarez, Víctor; Navarro, Xavier

    2015-05-13

    After peripheral nerve injury, axons are able to regenerate, although specific sensory reinnervation and functional recovery are usually worse for large myelinated than for small sensory axons. The mechanisms that mediate the regeneration of different sensory neuron subpopulations are poorly known. The Na(+)-K(+)-Cl(-) cotransporter 1 (NKCC1) is particularly relevant in setting the intracellular chloride concentration. After axotomy, increased NKCC1 phosphorylation has been reported to be important for neurite outgrowth of sensory neurons; however, the mechanisms underlying its effects are still unknown. In the present study we used in vitro and in vivo models to assess the differential effects of blocking NKCC1 activity on the regeneration of different types of dorsal root ganglia (DRGs) neurons after sciatic nerve injury in the rat. We observed that blocking NKCC1 activity by bumetanide administration induces a selective effect on neurite outgrowth and regeneration of myelinated fibers without affecting unmyelinated DRG neurons. To further study the mechanism underlying NKCC1 effects, we also assessed the changes in mitogen-activated protein kinase (MAPK) signaling under NKCC1 modulation. The inhibition of NKCC1 activity in vitro and in vivo modified pJNK1/2/3 expression in DRG neurons. Together, our study identifies a mechanism selectively contributing to myelinated axon regeneration, and point out the role of Cl(-) modulation in DRG neuron regeneration and in the activation of MAPKs, particularly those belonging to the JNK family. Copyright © 2015 the authors 0270-6474/15/357414-14$15.00/0.

  14. Protein kinase C (PKC) participates in acetaminophen hepatotoxicity through JNK dependent and independent signaling pathways

    PubMed Central

    Johnson, Heather S.; Gaarde, William A.; Han, Derick; Kaplowitz, Neil

    2013-01-01

    This study examines the role of protein kinase C (PKC) and AMP-activated kinase (AMPK) in acetaminophen (APAP) hepatotoxicity. Treatment of primary mouse hepatocytes with broad-spectrum PKC inhibitors (Ro-31-8245, Go6983), protected against APAP cytotoxicity despite sustained JNK activation. Broad-spectrum PKC inhibitor treatment enhanced p-AMPK levels and AMPK regulated survival-energy pathways including autophagy. AMPK inhibition by compound C or activation using an AMPK activator oppositely modulated APAP cytotoxicity, suggesting p-AMPK and AMPK regulated energy survival pathways particularly autophagy play a critical role in APAP cytotoxicity. Ro-31-8245 treatment in mice upregulated p-AMPK levels, increased autophagy (i.e. increased LC3-II formation, p62 degradation) and protected against APAP-induced liver injury, even in the presence of sustained JNK activation and translocation to mitochondria. In contrast, treatment of hepatocytes with classical PKC inhibitor (Go6976) protected against APAP by inhibiting JNK activation. Knockdown of PKC-α using antisense (ASO) in mice also protected against APAP-induced liver injury by inhibiting JNK activation. APAP treatment resulted in PKC-α translocation to mitochondria and phosphorylation of mitochondrial PKC substrates. JNK 1 and 2 silencing in vivo decreased APAP-induced PKC-α translocation to mitochondria, suggesting PKC-α and JNK interplay in a feed-forward mechanism to mediate APAP-induced liver injury. Conclusion: PKC-α and other PKC(s) regulate death (JNK) and survival (AMPK) proteins, to modulate APAP-induced liver injury. PMID:23873604

  15. Sorafenib suppresses JNK-dependent apoptosis through inhibition of ZAK kinase

    PubMed Central

    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.

    2015-01-01

    Sorafenib is FDA-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 5–10% rate of developing cutaneous squamous cell carcinoma/keratoacanthomas. Paradoxical activation of 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 JNK activation through the off-target inhibition of ZAK kinase. 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

  16. Taurochenodeoxycholic acid induces NR8383 cells apoptosis via PKC/JNK-dependent pathway.

    PubMed

    Wang, Xu; Zhang, Ziying; He, Xiuling; Mao, Wei; Zhou, Lei; Li, Peifeng

    2016-09-05

    Our former studies have suggested that taurochenodeoxycholic acid (TCDCA) as a signaling molecule shows obvious anti-inflammatory and immune regulation properties. In this research, we tentatively explored the potential effects and the possible mechanism that involve in the apoptotic process in NR8383 cells induced by TCDCA. Using flow cytometry analysis, we evaluated the apoptosis rate. Gene expression levels were determined by qPCR. The expressions of protein kinase C (PKC), Jun N-terminal kinase (JNK) and their phosphorylation were measured by Western Blot. We observed the activities of caspase-3 and caspase-8 with Caspase-Glo® regent. The results demonstrated that TCDCA dramatically improved the apoptosis rate of NR8383 cells in a concentration-dependent manner. In the meantime, PKC mRNA levels and activities were significantly augmented by TCDCA treatments. In addition, JNK, caspase-3 and caspase-8 mRNA expression levels and activities were increased by TCDCA, while they were markedly decreased by specific inhibitors. We conclude that TCDCA contributes to the apoptosis through the activation of the caspase cascade in NR8383 cells, and the PKC/JNK signaling pathway may be involved in this process. These results indicate that TCDCA may be a latent effective pharmaceutical product for apoptosis-related diseases. Copyright © 2016 Elsevier B.V. All rights reserved.

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

    PubMed Central

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

    2013-01-01

    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. PMID:23306653

  18. Epithelial Conduction in Hydromedusae

    PubMed Central

    Mackie, G. O.; Passano, L. M.

    1968-01-01

    Sarsia, Euphysa, and other hydromedusae have been studied by electrophysiological techniques and are found to have nonnervous conducting epithelia resembling those described earlier for siphonophores. Simple, non-muscular epithelia fire singly or repetitively following brief electrical stimuli. The pulses recorded with suction electrodes are biphasic, initially positive, and show amplitudes of 0.75–2.0 mv, durations of 5–15 msec, and velocities of 15–35 cm/sec with short refractory periods. In the swimming muscle (myoepithelium) 2.0–4.0 mv composite events lasting 150–300 msec are associated with contraction waves. Propagation in nonnervous epithelia is typically all-or-none, nondecremental, and unpolarized. The subumbrellar endoderm lamella conducts independently of the adjacent ectoderm. The lower regions of the tentacles do not show propagated epithelial events. The spread of excitation in conducting epithelia and associated effector responses are described. Examples are given of interaction between events seemingly conducted in the nervous system and those in nonnervous epithelia. Either system may excite the other. Spontaneous activity, however, appears to originate in the nervous system. Conduction in nonnervous tissues is unaffected by excess Mg++ in concentrations suppressing presumed nervous activity, although this may not be a wholly adequate criterion for distinguishing components of the two systems. Evidence from old work by Romanes is considered in the light of these findings and the general significance of epithelial conduction is discussed. PMID:4386662

  19. Epithelial-Mesenchymal Transition

    PubMed Central

    Klymkowsky, Michael W.; Savagner, Pierre

    2009-01-01

    Epithelial-mesenchymal transition (EMT) describes a series of rapid changes in cellular phenotype. During EMT, epithelial cells down-modulate cell-cell adhesion structures, alter their polarity, reorganize their cytoskeleton, and become isolated, motile, and resistant to anoikis. The term EMT is often applied to distinct biological events as if it were a single conserved process, but in fact EMT-related processes can vary in intensity from a transient loss of cell polarity to the total cellular reprogramming, as found by transcriptional analysis. Based on clinical observations, it is more appropriate in most cases to describe the emergence of an EMT-like phenotype during tumor progression. Although EMT implies complete trans-differentiation, EMT-like emphasizes the intermediary phenotype associated with tumor cell renewal and adaptation to specific microenvironments. Here, we categorize the various EMT-like phenotypes found in human carcinomas that, depending on the tumor type, may or not represent analogous stages in tumor progression. We based these categories on the global tumor phenotype. The tumor microenvironment, which is associated with stromal reactions, hypoxia, paucity of nutrients, impaired differentiation, and activation of various EMT-associated pathways, modulates overall tumor phenotype and leads to tumor heterogeneity. PMID:19342369

  20. 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. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Presence of pancreatic intraepithelial neoplasia-3 in a background of chronic pancreatitis in pancreatic cancer patients.

    PubMed

    Hwang, In Kyeom; Kim, Haeryoung; Lee, Yoon Suk; Kim, Jaihwan; Cho, Jai Young; Yoon, Yoo-Seok; Han, Ho-Seong; Hwang, Jin-Hyeok

    2015-10-01

    The clinical significance of pancreatic intraepithelial neoplasia (PanIN) lesions in non-neoplastic pancreata of pancreatic ductal adenocarcinoma (PDAC) patients remains controversial. As chronic inflammation has been recently demonstrated to promote dissemination of in situ precancerous lesions, we investigated the prognostic significance of PanINs associated with chronic pancreatitis (CP) in PDAC patients. This retrospective study analyzed 125 curatively resected PDAC specimens for the presence of PanIN and CP. Univariate and multivariate analyses were performed to identify significant predictive factors for poor disease-free survival (DFS) and overall survival (OS). Immunohistochemical staining for E-cadherin and S100A4, markers of epithelial-mesenchymal transition, was performed on resected specimens containing PanIN-3 lesions. CP was observed in 27.2% (34/125) and PanIN-3 in 25.6% (32/125) of specimens. In the presence of CP, PanIN-3 was significantly associated with decreased survival (DFS: 4.3 vs 15.5 months, P = 0.021; OS: 16.3 vs 30.9 months, P = 0.004). PanIN-3 was not a prognostic factor in the absence of CP. The presence of both PanIN-3 and CP was associated with a reduced survival compared to the other cases, in both univariate (DFS: P = 0.039; OS: P = 0.023) and multivariate (DFS: P = 0.020; OS: P = 0.076) analyses. Furthermore, E-cadherin loss and S100A4 expression were more frequently observed in PanIN-3 lesions of CP specimens than in those of non-CP specimens, although not statistically significant. PanIN-3 in association with CP is a significant prognostic factor for decreased survival in PDAC patients, suggesting that chronic inflammation may accelerate the progression of preinvasive high-grade PanIN. © 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

  2. Toxicity and response in cats with neoplasia treated with toceranib phosphate.

    PubMed

    Harper, Aaron; Blackwood, Laura

    2017-06-01

    Objectives Toceranib phosphate is a tyrosine kinase inhibitor licensed for the treatment of non-resectable Patnaik grade II/III recurrent cutaneous mast cell tumours in dogs. There is no information in cats regarding the tolerated dose, toxicity or tumour response of this drug. The aim of this study was to analyse retrospectively a cohort of cats with advanced neoplasia treated with toceranib to identify toxicity and response. Methods The medical records of the Small Animal Teaching Hospital were reviewed. Cats were included if they had received toceranib for at least 2 weeks for the treatment of histologically or cytologically confirmed neoplastic disease, and had at least one set of monitoring blood tests (haematology, biochemistry) performed after baseline tests. Toxicity was graded according to the Veterinary Comparative Oncology Group - common terminology criteria for adverse events(VCOG-CTCAE) and response was measured according to Response Evaluation In Solid Tumors (RECIST) criteria. Results Fourteen cats met the inclusion criteria, the majority of which (13/14) had received previous therapy (surgery, radiotherapy, chemotherapy). The most common tumour types were mast cell tumours or malignant epithelial tumours. Toxicity occurred in 10/14 cats - 10 cats had mild myelosuppression or gastrointestinal effects. Two cats developed severe hepatoxicity. One cat died from congestive heart failure, although whether this was related to toceranib therapy is unknown. Regarding response, one cat achieved complete response; two cats achieved partial response and five cats achieved stable disease: overall biological response rate was 57.1%. All of the cats that achieved either partial or complete response were treated for mast cell disease. Overall median duration of response was 90 days (range 14-570 days). None of the cats with squamous cell carcinoma achieved a response. Conclusions and relevance Toceranib phosphate is generally well tolerated in cats, with toxicity

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

    PubMed Central

    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

  4. 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.

  5. Pharmacological Intervention through Dietary Nutraceuticals in Gastrointestinal Neoplasia.

    PubMed

    Ullah, Mohammad F; Bhat, Showket H; Husain, Eram; Abu-Duhier, Faisel; Hadi, S M; Sarkar, Fazlul H; Ahmad, Aamir

    2016-07-03

    Neoplastic conditions associated with gastrointestinal (GI) tract are common worldwide with colorectal cancer alone accounting for the third leading rate of cancer incidence. Other GI malignancies such as esophageal carcinoma have shown an increasing trend in the last few years. The poor survival statistics of these fatal cancer diseases highlight the need for multiple alternative treatment options along with effective prophylactic strategies. Worldwide geographical variation in cancer incidence indicates a correlation between dietary habits and cancer risk. Epidemiological studies have suggested that populations with high intake of certain dietary agents in their regular meals have lower cancer rates. Thus, an impressive embodiment of evidence supports the concept that dietary factors are key modulators of cancer including those of GI origin. Preclinical studies on animal models of carcinogenesis have reflected the pharmacological significance of certain dietary agents called as nutraceuticals in the chemoprevention of GI neoplasia. These include stilbenes (from red grapes and red wine), isoflavones (from soy), carotenoids (from tomatoes), curcuminoids (from spice turmeric), catechins (from green tea), and various other small plant metabolites (from fruits, vegetables, and cereals). Pleiotropic action mechanisms have been reported for these diet-derived chemopreventive agents to retard, block, or reverse carcinogenesis. This review presents a prophylactic approach to primary prevention of GI cancers by highlighting the translational potential of plant-derived nutraceuticals from epidemiological, laboratory, and clinical studies, for the better management of these cancers through consumption of nutraceutical rich diets and their intervention in cancer therapeutics.

  6. 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

  7. Evaluation of Candidate Methylation Markers to Detect Cervical Neoplasia

    PubMed Central

    Shivapurkar, Narayan; Sherman, Mark E.; Stastny, Victor; Echebiri, Chinyere; Rader, Janet S.; Nayar, Ritu; Bonfiglio, Thomas A.; Gazdar, Adi F.; Wang, Sophia S.

    2009-01-01

    Objective Studies of cervical cancer and its immediate precursor, cervical intraepithelial neoplasia 3 (CIN3), have identified genes that often show aberrant DNA methylation and therefore, represent candidate early detection markers. We used quantitative PCR assays to evaluate methylation in five candidate genes (TNFRSF10C, DAPK1, SOCS3, HS3ST2 and CDH1) previously demonstrated as methylated in cervical cancer. Methods In this analysis, we performed methylation assays for the five candidate genes in 45 invasive cervical cancers, 12 histologically normal cervical specimens, and 23 liquid-based cervical cytology specimens confirmed by expert review as unequivocal demonstrating cytologic high-grade squamous intraepithelial lesions, thus representing the counterparts of histologic CIN3. Results We found hypermethylation of HS3ST2 in 93% of cancer tissues and 70% of cytology specimens interpreted as CIN3; hypermethylation of CDH1 was found in 89% of cancers and 26% of CIN3 cytology specimens. Methylation of either HS3ST2 or CDH1 was observed in 100% of cervical cancer tissues and 83% of CIN3 cytology specimens. None of the five genes showed detectable methylation in normal cervical tissues. Conclusion Our data support further evaluation of HS3ST2 and CDH1 methylation as potential markers of cervical cancer and its precursor lesions. PMID:17894941

  8. 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.

  9. 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.

  10. Classification systems in Gestational trophoblastic neoplasia - Sentiment or evidenced based?

    PubMed

    Parker, V L; Pacey, A A; Palmer, J E; Tidy, J A; Winter, M C; Hancock, B W

    2017-05-01

    The classification system for Gestational trophoblastic neoplasia (GTN) has proved a controversial topic for over 100years. Numerous systems simultaneously existed in different countries, with three main rival classifications gaining popularity, namely histological, anatomical and clinical prognostic systems. Until 2000, prior to the combination of the FIGO and WHO classifications, there was no worldwide consensus on the optimal classification system, largely due to a lack of high quality data proving the merit of one system over another. Remarkably, a validated, prospectively tested classification system is yet to be conducted. Over time, increasing criticisms have emerged regarding the currently adopted combined FIGO/WHO classification system, and its ability to identify patients most likely to develop primary chemotherapy resistance or disease relapse. This is particularly pertinent for patients with low-risk disease, whereby one in three patients are resistant to first line therapy, rising to four out of five women who score 5 or 6. This review aims to examine the historical basis of the GTN classification systems and critically appraise the evidence on which they were based. This culminates in a critique of the current FIGO/WHO prognostic system and discussion surrounding clinical preference versus evidence based practice. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. 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.

  12. Screening, Surveillance, and Treatment of Anal Intraepithelial Neoplasia

    PubMed Central

    Long, Kevin C.; Menon, Raman; Bastawrous, Amir; Billingham, Richard

    2016-01-01

    The prevalence of anal intraepithelial neoplasia has been increasing, especially in high-risk patients, including men who have sex with men, human immunodeficiency virus positive patients, and those who are immunosuppressed. Several studies with long-term follow-up have suggested that rate of progression from high-grade squamous intraepithelial lesions to invasive anal cancer is ∼ 5%. This number is considerably higher for those at high risk. Anal cytology has been used to attempt to screen high-risk patients for disease; however, it has been shown to have very little correlation to actual histology. Patients with lesions should undergo history and physical exam including digital rectal exam and standard anoscopy. High-resolution anoscopy can be considered as well, although it is of questionable time and cost–effectiveness. Nonoperative treatments include expectant surveillance and topical imiquimod or 5-fluorouracil. Operative therapies include wide local excision and targeted ablation with electrocautery, infrared coagulation, or cryotherapy. Recurrence rates remain high regardless of treatment delivered and surveillance is paramount, although optimal surveillance regimens have yet to be established. PMID:26929753

  13. Alopecia universalis in a dog with testicular neoplasia.

    PubMed

    Outerbridge, Catherine A; White, Stephen D; Affolter, Verena K

    2016-12-01

    To describe a case of testicular neoplasia and alopecia universalis in a dog, and successful treatment of the latter with ciclosporin. Twelve-year-old intact male wirehaired fox terrier. Castration, skin biopsy for histopathology, lymphocyte immunophenotyping and clonality analysis of the canine T-cell receptor gamma locus (TCRγ) rearrangement. The dog presented with symmetrical generalized alopecia. Testicular enlargement was noted which on castration was determined to be caused by bilateral interstitial cell tumours, Sertoli cell tumours and a unilateral seminoma. During the four months after castration the alopecia became more severe and widespread. Histopathology of the skin showed moderate, multifocal, mural folliculitis, peribulbar mucinosis and lymphocytic bulbitis, and targeting of anagen hair follicles. Immunophenotyping of the infiltrate showed a population of well-differentiated, small CD3-positive T lymphocytes, some expressing CD4 and others CD8. Molecular analysis revealed a polyclonal lymphocytic infiltrate, substantiating the diagnosis of alopecia areata rather than lymphoma. Treatment with ciclosporin (4.6 mg/kg) and ketoconazole (4.6 mg/kg) resulted in complete hair regrowth. Ciclosporin treatment, in combination with ketoconazole, can be effective for treatment of alopecia universalis in the dog. Alopecia universalis may present with clinically noninflammatory, symmetrical, generalized alopecia, mimicking an endocrine alopecia, and skin biopsies are needed to confirm the diagnosis. © 2016 ESVD and ACVD.

  14. The parathyroid glands in multiple endocrine neoplasia type 2b.

    PubMed Central

    Carney, J. A.; Roth, S. I.; Heath, H.; Sizemore, G. W.; Hayles, A. B.

    1980-01-01

    The histologic features of 21 parathyroid glands obtained from 16 Mayo Clinic patients aged 2 to 52 years who had multiple endocrine neoplasia type 2b (MEN 2b) were evaluated. The findings were correlated with the patients' ages and with the serum concentrations of calcium (15 patients), phosphorus (14 patients), and immunoreactive parathyroid hormone (iPTH) (11 patients), and with the response of serum iPTH to calcium infusion (6 patients). We also studied the histologic features of 13 parathyroid glands obtained from 8 patients not seen at the Mayo Clinic with MEN 2b. The microscopic appearance of the glands was normal in patients under the age of 17; with increased age, the glands did not exhibit normal involution, and an appearance consistent with mild chief-cell hyperplasia was evident. This abnormality was not associated with clinical or laboratory manifestations of hyperparathyroidism. We presently believe that parathyroidectomy for the disorder is not justified. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:7377288

  15. Microscopic features of colorectal neoplasia in inflammatory bowel diseases

    PubMed Central

    Bressenot, Aude; Cahn, Virginie; Danese, Silvio; Peyrin-Biroulet, Laurent

    2014-01-01

    The risk of developing dysplasia leading to colorectal cancer (CRC) is increased in both ulcerative colitis and Crohn’s disease. The prognosis of CRC may be poorer in patients with inflammatory bowel disease (IBD) than in those without IBD. Most CRCs, in general, develop from a dysplastic precursor lesion. The interpretation by the pathologist of the biopsy will guide decision making in clinical practice: colonoscopic surveillance or surgical management. This review summarizes features of dysplasia (or intraepithelial neoplasia) with macroscopic and microscopic characteristics. From an endoscopic (gross) point of view, dysplasia may be classified as flat or elevated (raised); from a histological point of view, dysplasia is separated into 3 distinct categories: negative for dysplasia, indefinite for dysplasia, and positive for dysplasia with low- or high-grade dysplasia. The morphologic criteria for dysplasia are based on a combination of cytologic (nuclear and cytoplasmic) and architectural aberrations of the crypt epithelium. Immunohistochemical and molecular markers for dysplasia are reviewed and may help with dysplasia diagnosis, although diagnosis is essentially based on morphological criteria. The clinical, epidemiologic, and pathologic characteristics of IBD-related cancers are, in many aspects, different from those that occur sporadically in the general population. Herein, we summarize macroscopic and microscopic features of IBD-related colorectal carcinoma. PMID:24696602

  16. Imiquimod in cervical, vaginal and vulvar intraepithelial neoplasia: a review.

    PubMed

    de Witte, C J; van de Sande, A J M; van Beekhuizen, H J; Koeneman, M M; Kruse, A J; Gerestein, C G

    2015-11-01

    Human papillomavirus (HPV) infection is in the vast majority of patients accountable for the development of vulvar, cervical and vaginal intraepithelial neoplasia (VIN, CIN, VAIN); precursors of vulvar, cervical and vaginal cancers. The currently preferred treatment modality for high grade VIN, CIN and VAIN is surgical excision. Nevertheless surgical treatment is associated with adverse pregnancy outcomes and recurrence is not uncommon. The aim of this review is to present evidence on the efficacy, safety and tolerability of imiquimod (an immune response modifier) in HPV-related VIN, CIN and VAIN. A search for papers on the use of imiquimod in VIN, CIN and VAIN was performed in the MEDLINE, EMBASE and Cochrane library databases. Data was extracted and reviewed. Twenty-one articles met the inclusion criteria and were analyzed; 16 on VIN, 3 on CIN and 2 on VAIN. Complete response rates in VIN ranged from 5 to 88%. Although minor adverse effects were frequently reported, treatment with imiquimod was well tolerated in most patients. Studies on imiquimod treatment of CIN and VAIN are limited and lack uniformly defined endpoints. The available evidence however, shows encouraging effect. Complete response rates for CIN 2-3 and VAIN 1-3 ranged from 67 to 75% and 57 to 86% respectively. More randomized controlled trials on the use of imiquimod in CIN, VAIN and VIN with extended follow-up are necessary to determine the attributive therapeutic value in these patients.

  17. Id2 Is Dispensable for Myc-Induced Epidermal Neoplasia

    PubMed Central

    Murphy, Daniel J.; Swigart, Lamorna Brown; Israel, Mark A.; Evan, Gerard I.

    2004-01-01

    We have previously described a transgenic mouse model of epidermal neoplasia wherein expression of a switchable form of c-Myc, MycERTAM, is targeted to the postmitotic suprabasal keratinocytes of murine epidermis via the involucrin promoter. Sustained activation of c-MycERTAM results in a progressive neoplastic phenotype characterized by aberrant ectopic proliferation and delayed differentiation of suprabasal keratinocytes, culminating in papillomatosis. Transcription of the Id2 gene is regulated by Myc family proteins. Moreover, Id2 is implicated as a pivotal determinant of cell fate in multiple lineages and has a demonstrated role in mediating Myc-dependent cell proliferation in vitro through its interaction with retinoblastoma protein. Using Id2 nullizygous mice, we assessed in vivo the requirement for Id2 in mediating Myc-induced papilloma formation in skin. We show that absence of Id2 has no discernible impact on any measurable attribute of Myc function or on the timing or extent of eventual tumor formation. Thus, our data argue against any essential role for Id2 in mediating Myc action in vivo. PMID:14966287

  18. Ocular Surface Squamous Neoplasia Associated with Atopic Keratoconjunctivitis

    PubMed Central

    Shah, Ankit; Espana, Edgar M.; Singh, Arun D.

    2017-01-01

    Purpose To describe 2 cases of invasive squamous cell carcinoma that originated in the setting of severe atopic keratoconjunctivitis (AKC). Methods Case one involved a 73-year-old male with atopic eczema and severe AKC who developed a limbal lesion suspicious for ocular surface squamous neoplasia (OSSN). Slit-lamp examination was significant for a new sessile lesion in the temporal limbal region of the left eye. The lesion was treated with excisional biopsy and cryotherapy. Topical therapy with mitomycin C, topical interferon alpha 2b, and topical 5-fluorouracil provided only partial control. Exenteration was eventually needed. Case two involved a 53-year-old male with history of severe AKC and eczema. Computed tomography imaging showed an infiltrative mass of the right orbit. Incisional biopsies confirmed conjunctival squamous cell carcinoma of both sides (invasive in the right eye, in situ in the left eye). Exenteration was needed for control of invasive carcinoma in the right eye. Results Squamous cell carcinoma was treated without success in spite of surgical excision and aggressive treatment with multiple topical agents and multiple applications of cryotherapy. Orbital exenteration was needed in both cases. Conclusion Chronic inflammation associated with AKC may be a risk factor for the development of bilateral, diffuse, invasive, and recurrent OSSN that may require exenteration. PMID:28275599

  19. 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

  20. Dietary habits of colorectal neoplasia patients in comparison to their first-degree relatives

    PubMed Central

    Kajzrlikova, Ivana Mikoviny; Vitek, Petr; Chalupa, Josef; Dite, Petr

    2014-01-01

    AIM: To compare the dietary habits between colorectal neoplasia patients, their first-degree relatives, and unrelated controls. METHODS: From July 2008 to April 2011, we collected epidemiological data relevant to colorectal cancer from patients with colorectal neoplasias, their first-degree relatives, and also from a control group consisting of people referred for colonoscopy with a negative family history of colorectal cancer and without evidence of neoplasia after colonoscopic examination. The first-degree relatives were divided into two groups following the colonoscopic examination: (1) patients with neoplasia or (2) patients without neoplasia. Dietary habits of all groups were compared. A χ2 test was used to assess the association between two dichotomous categorical variables. RESULTS: The study groups consisted of 242 patients with colorectal neoplasias (143 men, 99 women; mean age: 64 ± 12 years) and 160 first-degree relatives (66 men, 94 women; mean age: 48 ± 11 years). Fifty-five of the first-degree relatives were found to have a neoplastic lesion upon colonoscopy, while the remaining 105 were without neoplasia. The control group contained 123 individuals with a negative family history for neoplastic lesions (66 men, 57 women; mean age: 54 ± 12 years). Two hypotheses were tested. In the first, the dietary habits of first-degree relatives with neoplasia were more similar to those of patients with neoplasia, while the dietary habits of first-degree relatives without neoplasia were similar to those of the control group. In the second, no sex-related differences in dietary habits were expected between the particular groups. Indeed, no significant differences were observed in the dietary habits between the groups of patients, controls and first-degree relatives with/without neoplastic lesions. Nevertheless, statistically significant sex-related differences were observed in all groups, wherein women had healthier dietary habits than men. CONCLUSION: In all

  1. 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

  2. Hydraulic fracture during epithelial stretching

    NASA Astrophysics Data System (ADS)

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

    2015-03-01

    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 manoeuvres. 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.

  3. Hydraulic fracture during epithelial stretching.

    PubMed

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

    2015-03-01

    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 manoeuvres. 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.

  4. 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. © 2016 Society for Endocrinology.

  5. Extensive focal epithelial hyperplasia.

    PubMed

    Hashemipour, Maryam Alsadat; Shoryabi, Ali; Adhami, Shahrzad; Mehrabizadeh Honarmand, Hoda

    2010-01-01

    Heck's disease or focal epithelial hyperplasia is a benign contagious disease caused by human papillomavirus types 13 or 32. It occurs with low frequency in the Iranian population. This condition is characterized by the occurrence of multiple, small papules or nodules in the oral cavity, especially on the labial and buccal mucosa and tongue. In some populations, up to 39% of children are affected. Conservative surgical excision of lesions may be performed for diagnostic or aesthetic purposes. The risk of recurrence after this therapy is minimal, and there seems to be no malignant transformation potential. In the present work, we presented the clinical case of a 12-year-old Iranian girl with oral lesions that clinically and histologically correspond to Heck's disease.

  6. Thiazolidinedione Therapy Is Not Associated with Increased Colonic Neoplasia Risk in Patients with Diabetes Mellitus

    PubMed Central

    Lewis, James D.; Capra, Angela M.; Achacoso, Ninah S.; Ferrara, Assiamira; Levin, Theodore R.; Quesenberry, Charles P.; Habel, Laurel A.

    2008-01-01

    Background & Aims Diabetes mellitus is associated with an increased risk of colorectal cancer. Thiazolidinediones, which are ligands for PPARγ, are widely used to treat patients with diabetes. PPARγ is highly expressed in the colon and exposure to thiazolidinediones has been proposed to affect the risk for colorectal neoplasia. Studies using in vitro models suggest that thiazolidinediones have anti-neoplastic effects, whereas in vivo studies have produced mixed results--some indicate an increased risk for intestinal tumors. This study examined the association between PPARγ-targeted therapies and the risk of colonic neoplasia in patients with diabetes. Methods We conducted 3 retrospective case-control studies nested within the cohort of diabetic patients that were cared for within the Kaiser Permanente of Northern California system from 1994 to 2005. Case subjects were those with colonic neoplasia identified at the time of colonoscopy (study-1), sigmoidoscopy (study-2), or at follow-up lower endoscopy (study-3). Controls had no neoplasia identified at the endoscopic exam. A minimum of 1 year of therapy was used to define medication exposure. Results 14,086 patients were included. Among patients undergoing colonoscopy, there was an inverse association between thiazolidinedione exposure and prevalence of neoplasia (adjusted OR=0.73, 95% CI 0.57–0.92); however, this was not evident among patients without anemia (adjusted OR= 0.97, 95% CI 0.64–1.49). Significant associations between any or long-term thiazolidinedione use and colonic neoplasia were not observed among patients undergoing sigmoidoscopy or serial lower endoscopies. Conclusions These results indicate that thiazolidinedione therapy is not associated with an increased risk for colonic neoplasia. PMID:18930061

  7. A prognostic model for advanced colorectal neoplasia recurrence.

    PubMed

    Liu, Lin; Messer, Karen; Baron, John A; Lieberman, David A; Jacobs, Elizabeth T; Cross, Amanda J; Murphy, Gwen; Martinez, Maria Elena; Gupta, Samir

    2016-10-01

    Following colonoscopic polypectomy, US Multisociety Task Force (USMSTF) guidelines stratify patients based on risk of subsequent advanced neoplasia (AN) using number, size, and histology of resected polyps, but have only moderate sensitivity and specificity. We hypothesized that a state-of-the-art statistical prediction model might improve identification of patients at high risk of future AN and address these challenges. Data were pooled from seven prospective studies which had follow-up ascertainment of metachronous AN within 3-5 years of baseline polypectomy (combined n = 8,228). Pooled data were randomly split into training (n = 5,483) and validation (n = 2,745) sets. A prognostic model was developed using best practices. Two risk cut-points were identified in the training data which achieved a 10 percentage point improvement in sensitivity and specificity, respectively, over current USMSTF guidelines. Clinical benefit of USMSTF versus model-based risk stratification was then estimated using validation data. The final model included polyp location, prior polyp history, patient age, and number, size and histology of resected polyps. The first risk cut-point improved sensitivity but with loss of specificity. The second risk cut-point improved specificity without loss of sensitivity (specificity 46.2 % model vs. 42.1 % guidelines, p < 0.001; sensitivity 75.8 % model vs. 74.0 % guidelines, p = 0.64). Estimated AUC was 65 % (95 % CI: 62-69 %). This model-based approach allows flexibility in trading sensitivity and specificity, which can optimize colonoscopy over- versus underuse rates. Only modest improvements in prognostic power are possible using currently available clinical data. Research considering additional factors such as adenoma detection rate for risk prediction appears warranted.

  8. Dietary methionine restriction inhibits prostatic intraepithelial neoplasia in TRAMP mice.

    PubMed

    Sinha, Raghu; Cooper, Timothy K; Rogers, Connie J; Sinha, Indu; Turbitt, William J; Calcagnotto, Ana; Perrone, Carmen E; Richie, John P

    2014-12-01

    Prostate cancer (PCa) is a major aging-related disease for which little progress has been made in developing preventive strategies. Over the past several years, methionine restriction (MR), the feeding of a diet low in methionine (Met), has been identified as an intervention which significantly extends lifespan and reduces the onset of chronic diseases, including cancer, in laboratory animals. We, therefore, hypothesized that MR may be an effective strategy for inhibiting PCa. Control (0.86% Met) or MR (0.12% Met) diets were fed to 5-week old TRansgenic Adenocarcinoma of the Mouse Prostate (TRAMP) mice, a well-characterized model for PCa. The mice were sacrificed at 16 weeks of age and prostate and other tissues were harvested for histological and biochemical analyses. As previously reported, MR was associated with a decrease in body weight which was not associated with lowered food intake. MR led to significant reductions in the development of Prostatic Intraepithelial Neoplasia (PIN) lesions, specifically in the anterior and dorsal lobes of the prostate where the incidence of high-grade PIN was reduced by ∼50% (P < 0.02). The reduction in PIN severity was associated with 46-64% reductions in cell proliferation rates (P < 0.02) and plasma IGF-1 levels (P < 0.0001), which might, in part, explain the effects on carcinogenesis. Additionally, no adverse consequences of MR on immune function were observed in the TRAMP mice. Overall, these findings indicate that MR is associated with a reduction in prostate cancer development in the TRAMP model and supports the continued development of MR as a potential PCa prevention strategy. © 2014 Wiley Periodicals, Inc.

  9. Human papillomavirus genotypes in cervical intraepithelial neoplasia grade 3.

    PubMed

    Castle, Philip E; Schiffman, Mark; Wheeler, Cosette M; Wentzensen, Nicolas; Gravitt, Patti E

    2010-07-01

    There are few large case series describing the human papillomavirus (HPV) genotypes found in women diagnosed with rigorously reviewed cervical intraepithelial neoplasia grade 3 (CIN3), cervical precancer. The Atypical Squamous Cells of Undetermined Significance (ASCUS) and Low-Grade Squamous Intraepithelial Lesion (LSIL) Triage Study (ALTS) was a clinical trial to evaluate the best management strategies for women with equivocal (ASCUS) or mildly abnormal (LSIL) Pap tests. During enrollment and the 2-year follow-up, 608 women had a histopathologic diagnosis of CIN3 and PCR-based HPV genotyping results on cervical specimens. The genotyping results were ranked hierarchically according to cancer risk: HPV16 > other carcinogenic HPV > noncarcinogenic HPV > PCR negative. Among the 608 women diagnosed with CIN3, 601 (98.8%) cases were positive for any HPV genotype and 95.4% for any carcinogenic HPV. HPV16 (59.9%), HPV31 (18.1%), HPV52 (14.8%), HPV51 (14.0%), and HPV18 (13.2%) were the five most common HPV genotypes detected. Younger age, consensus histologic confirmation, smoking, and multiparity increased the likelihood of testing HPV 16 positive. Specifically, HPV16-positive CIN3 occurred at a younger age than CIN3 positive for other carcinogenic HPV genotypes (median of 23.5 years versus 25 years, respectively; P = 0.0003, Kruskal-Wallis). HPV16-positive CIN3 was more commonly diagnosed in younger women (versus older women), with consensus diagnosis (versus some disagreement between reviewers), and in smokers (versus nonsmokers), and was less commonly diagnosed in multiparous women compared CIN3 positive for other carcinogenic HPV genotypes. In populations vaccinated against HPV16 (and HPV18), the median age of CIN3 in women with ASCUS and LSIL cytology should shift to older ages, possibly permitting later age at first screening.

  10. [The premalignant disease of the endometrium: endometrial intraepithelial neoplasia].

    PubMed

    Francz, Mónika

    2008-03-01

    The WHO 1994 classification for endometrial hyperplasias is based on the morphologic features of the lesions. This system characterizes the nuclear cytologic morphology as typical or atypical and describes the glandular architectural pattern as simple or complex. The main problem of this classification is the poor reproducibility. Although the predictive value of the atypical category is high, there are many typical hyperplasia cases with cancer progression. Modern molecular data related to endometrial tumorigenesis and precise computerized morphometric analysis have identified the lesion that may be considered as a precursor of endometrioid adenocarcinoma. By definition, this endometrial intraepithelial neoplasia (EIN) is a clonal proliferation of architecturally and cytologically altered endometrial glands which are prone to malignant transformation to endometrioid (type I) endometrial adenocarcinoma. The morphometric basis of EIN diagnosis is the D-score (DS), which is a logical combination of three morphometric features that represent the glandular complexity, glandular volume and cytological alterations. PTEN inactivation and K-ras mutation are the earliest genetic changes that can be revealed in these lesions. Hyperplasia cases that do not fit into the EIN categories are considered as benign or hormonal endometrial hyperplasia. This is the theoretical basis of a new classification system in premalignant endometrial diseases. Retrospective clinical data proved the high predictive value of the EIN scheme, so the decision on therapy can be more established. The reproducibility is excellent with application of precise definitions and PTEN immunohistochemistry. In the "Blue book" published in 2003 the WHO introduces the new morphometric- and molecular-based EIN system, and recommends it as an alternative classification method.

  11. Anal intraepithelial neoplasia: A review of diagnosis and management

    PubMed Central

    Roberts, Joseph R; Siekas, Lacey L; Kaz, Andrew M

    2017-01-01

    Anal intraepithelial neoplasia (AIN) is a premalignant lesion of the anal mucosa that is a precursor to anal cancer. Although anal cancer is relatively uncommon, rates of this malignancy are steadily rising in the United States, and among certain high risk populations the incidence of anal cancer may exceed that of colon cancer. Risk factors for AIN and anal cancer consist of clinical factors and behaviors that are associated with the acquisition and persistence of human papilloma virus (HPV) infection. The strongest HPV-associated risk factors are HIV infection, receptive anal intercourse, and high risk sexual behavior. A history of HPV-mediated genital cancer, which suggests infection with an oncogenic HPV strain, is another risk factor for AIN/anal cancer. Because progression of AIN to anal cancer is known to occur in some individuals over several years, screening for AIN and early anal cancer, as well as treatment of advanced AIN lesions, is reasonable in certain high-risk populations. Although randomized controlled trials evaluating screening and treatment outcomes are lacking, experts support routine screening for AIN in high risk populations. Screening is performed using anal cytological exams, similar to those performed in cervical cancer screening programs, along with direct tissue evaluation and biopsy via high resolution anoscopy. AIN can be treated using topical therapies such as imiquimod, 5-flurouracil, and trichloroacetic acid, as well as ablative therapies such as electrocautery and laser therapy. Reductions in AIN and anal cancer rates have been shown in studies where high-risk populations were vaccinated against the oncogenic strains of HPV. Currently, the CDC recommends both high-risk and average-risk populations be vaccinated against HPV infection using the quadrivalent or nonavalent vaccines. It is important for clinicians to be familiar with AIN and the role of HPV vaccination, particularly in high risk populations. PMID:28255426

  12. Anal intraepithelial neoplasia: A review of diagnosis and management.

    PubMed

    Roberts, Joseph R; Siekas, Lacey L; Kaz, Andrew M

    2017-02-15

    Anal intraepithelial neoplasia (AIN) is a premalignant lesion of the anal mucosa that is a precursor to anal cancer. Although anal cancer is relatively uncommon, rates of this malignancy are steadily rising in the United States, and among certain high risk populations the incidence of anal cancer may exceed that of colon cancer. Risk factors for AIN and anal cancer consist of clinical factors and behaviors that are associated with the acquisition and persistence of human papilloma virus (HPV) infection. The strongest HPV-associated risk factors are HIV infection, receptive anal intercourse, and high risk sexual behavior. A history of HPV-mediated genital cancer, which suggests infection with an oncogenic HPV strain, is another risk factor for AIN/anal cancer. Because progression of AIN to anal cancer is known to occur in some individuals over several years, screening for AIN and early anal cancer, as well as treatment of advanced AIN lesions, is reasonable in certain high-risk populations. Although randomized controlled trials evaluating screening and treatment outcomes are lacking, experts support routine screening for AIN in high risk populations. Screening is performed using anal cytological exams, similar to those performed in cervical cancer screening programs, along with direct tissue evaluation and biopsy via high resolution anoscopy. AIN can be treated using topical therapies such as imiquimod, 5-flurouracil, and trichloroacetic acid, as well as ablative therapies such as electrocautery and laser therapy. Reductions in AIN and anal cancer rates have been shown in studies where high-risk populations were vaccinated against the oncogenic strains of HPV. Currently, the CDC recommends both high-risk and average-risk populations be vaccinated against HPV infection using the quadrivalent or nonavalent vaccines. It is important for clinicians to be familiar with AIN and the role of HPV vaccination, particularly in high risk populations.

  13. Metastatic multiple endocrine neoplasia type 1: report of one case

    PubMed Central

    Huang, Cheng; Zhu, Xiaodong; Han, Xu

    2016-01-01

    A 46-year-old Chinese woman was admitted to our hospital because of presence of space-occupying lesions in the liver for 2 months in April, 2015. She had a family history of multiple endocrine neoplasia type 1 (MEN1) and physical examination is unremarkable. Previously, she has performed surgery for primary pituitary tumor in 2002 and radiosurgery for its recurrence. Around December 2014, she suffered from abdominal discomfort associated with regurgitation and gastroscopy revealed “gastroduodenal ulcers”, along with elevated gastrin. Next, both magnetic resonance and computed tomography imaging showed multiple intrahepatic lesions, the PET-CT unveiled uptake pattern of 18F-FDG in duodenum and multiple intrahepatic lesions, resembling the appearance of metastatic gastrinoma. The octreotide scan gave identical results. The parathyroid SPECT scans showed abnormal concentrations of radioactivity in right parathyroid. She also had an elevated serum chromogranin A (CgA) level. There was medical evidence to show that she is metastatic MEN1. Although multiple liver metastases, they were considered to be resectable after MDT consultation. The intraoperative exploration found a 1.5 cm tumor on the surface of the tail of the pancreas, a 12 cm retroperitoneal lipoma and two liver metastases, sized 3.5 cm and 1.5 cm, respectively. All these tumors were completely removed. For pancreatic tumor, pathological findings met the diagnostic criteria of neuroendocrine tumor (NET) (G2). Immunohistochemistry revealed neuroendocrine areas were diffusely positive for ATRX, DAXX, SSR2, SSR5 and CgA. For lipoma, the FISH results were negative for CDK4 and MDM2 genes. Postoperatively, adjuvant therapy with octreotide was applied. This case suggested that, as for metastatic gastrinoma, a potentially curative surgical debulking should be considered when a resection of complete or more than 90% of metastatic lesions along with the primary site could be achieved, which is helpful to control

  14. 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.

  15. Second Curettage for Low-Risk Nonmetastatic Gestational Trophoblastic Neoplasia.

    PubMed

    Osborne, Raymond J; Filiaci, Virginia L; Schink, Julian C; Mannel, Robert S; Behbakht, Kian; Hoffman, James S; Spirtos, Nick M; Chan, John K; Tidy, John A; Miller, David S

    2016-09-01

    To evaluate the efficacy and safety of second uterine curettage in lieu of chemotherapy for patients with low-risk, nonmetastatic gestational trophoblastic neoplasia (GTN) and to evaluate whether response to second curettage is independent of patient age, World Health Organization (WHO) risk score, registration human chorionic gonadotropin (hCG) level, lesion size, and depth of myometrial invasion measured on ultrasound examination. This was a cooperative group multicenter prospective phase II study. Prestudy testing included quantitative hCG level, pelvic ultrasonography, and chest radiography. Patients were categorized according to WHO risk scoring criteria (low risk with a score of 0-6). Sixty-four women with newly diagnosed low-risk, nonmetastatic GTN were enrolled. Four patients were excluded. Twenty-four patients (40%) (lower 95% confidence limit 27.6%) were cured after second curettage. An additional two patients (3%) achieved a complete response but did not complete follow-up. Overall, 26 of 60 patients were able to avoid chemotherapy. Surgical failure was observed in 34 women (59%) and was more common in women 19 years old or younger or 40 years old or older. One case of grade 1 uterine perforation was successfully managed by observation. Four grade 1 and one grade 3 uterine hemorrhages were reported. New metastatic disease (lung) was identified in one of these women after second curettage. In three patients (surgical failures), the second curettage pathology was placental site trophoblastic tumor, and it was placental nodule in one additional patient. Second uterine curettage as initial treatment for low-risk, nonmetastatic GTN cures 40% of patients without significant morbidity. ClinicalTrials.gov, https://clinicaltrials.gov/, NCT00521118.

  16. Salvage chemotherapy for gestational trophoblastic neoplasia: Utility or futility?

    PubMed

    Essel, Kathleen G; Bruegl, Amanda; Gershenson, David M; Ramondetta, Lois M; Naumann, R Wendel; Brown, Jubilee

    2017-07-01

    To determine the efficacy of chemotherapy after failed initial treatment in patients with high risk gestational trophoblastic neoplasia (GTN). We performed a retrospective IRB-approved chart review of all patients with GTN seen at a single institution from 1985 to 2015, including all patients who failed initial treatment. We summarized clinical characteristics with descriptive statistics and estimated progression-free survival (PFS) and overall survival (OS) with the Kaplan-Meier method. Of 68 identified patients, 38 required >2 chemotherapy regimens. Patients were treated for GTN (n=53), including choriocarcinoma, persistent GTN, and invasive mole; for placental site trophoblastic tumor (PSTT) (n=5); and for intermediate trophoblastic tumor (ITT) (n=10). Patients with GTN had a median of 2 salvage regimens, median PFS of 4.0months, and median OS was not reached at median follow-up of 71.2months. Active regimens included EMACO, MAC, BEP, platinum- and etoposide-based combination therapies, and ICE; 8 of 53 patients died of disease (DOD). Patients with PSTT had a median of 3 salvage regimens, median PFS of 2.8months, and median OS of 38.8months. Active regimens included ICE and EMA-EP; 4 of 5 patients DOD. Patients with ITT had a median of 3 salvage regimens, median PFS of 4.1months, and median OS of 38.2months. Active regimens included liposomal doxorubicin, platinum-containing regimens, EMA-CO, and EMA-EP; 7 of 10 patients DOD. Several salvage chemotherapy regimens demonstrate activity in high risk GTN. Multiple regimens may be required and cure is not universal. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. [Pleuropulmonary metastases originating from extra-thoracic neoplasia].

    PubMed

    Badri, Farid; Batahar, Salma Ait; Idrissi, Safae El; Sajiai, Hafsa; Serhane, Hind; Amro, Lamyae

    2017-01-01

    The lungs receive the entire venous drainage of the body. This explains the high incidence of pleuropulmonary metastases originating from several cancers. The goal of this is to study the clinical manifestations of pleuro-pulmonary metastases originating from extra-thoracic cancers. We conducted a retrospective study of patients with pleuro-pulmonary metastasis whose data were collected in our department between January 2006 and december 2014. 76 patient medical records were studied. The average age was 50 years (aged 21-89 years) with a male predominance in 57.8% of cases. Clinical symptoms were mainly cough (32.8% of cases), dyspnea (23.7% of cases) and hemoptysis (11.2%). Primary cancers responsible for various pleuro-pulmonary metastases found in our case series were dominated by breast cancers in 27.6% of cases, gastro-intestinal cancers in 15.8% of cases, genital cancers in 9, 2% of cases, sarcomas in 7.8% of cases, renal cancers in 5.2% of cases, bladder cancers in 5.2% of cases, prostate cancers in 3.9% cases, ENT cancers in 3.9% of cases, thyroid cancers in 3.9% of cases, skin cancers in 2.6% of cases and cancers of unknown primary origin in 14.4% of cases respectively. Several radiologic features of pleuro-pulmonary metastases have been found in our case series; they can be isolated or combined. The most common radiologic aspect was multiple pulmonary nodules in 52.6% of cases, followed by pleurisies in 34.2% of cases, diffuse micronodules in 23.6% of cases and a solitary nodule in 3.94% of cases. Secondary pleuropulmonary cancers are frequent. They come in 3rd place after lymph nodes and liver metastases and are found in 30% of autopsies of patients with neoplasia.

  18. 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

  19. Anal intraepithelial neoplasia: a single centre 19 year review.

    PubMed

    Cotter, M B; Kelly, M E; O'Connell, P R; Hyland, J; Winter, D C; Sheahan, K; Gibbons, D

    2014-10-01

    There is debate about whether the traditional three-tiered grading of anal intraepithelial neoplasia (AIN) should be replaced by a more reproducible two-tiered system. In this study, we review our experience with AIN to determine the most suitable classification system. We performed a retrospective review of all histological reports over a 19 year period. All specimens were graded on haemataloxin and eosin appearance and those with dysplasia had immunohistochemistry for p16 and Ki67 performed. Cases included 25 condyloma acuminata, 11 dysplastic cases and 24 invasive squamous cell carcinomas. On review, 18 were classified as condyloma acuminata without dysplasia. Seven had AIN I, five had AIN II and six had AIN III when using a three-tiered system. All cases classified as dysplastic (n = 18) showed an increased proliferation index as measured by Ki67. p16 positivity was seen in all AIN III, two AIN II and none of the AIN I cases. Recurrence was not observed in any of the AIN I cases. Five of eleven AIN II and AIN III cases recurred or persisted at a similar, higher or lower grade. Both of the AIN II cases which recurred or persisted were p16 positive. None of the AIN II cases that were p16 negative recurred. Three of the p16-positive AIN III cases did not recur. None of the 18 AIN cases progressed to carcinoma. The findings support the slow progression of AIN as described in the literature. In our small series, a two-tiered system with further subclassification of the traditional AIN II group using p16 appears to be clinically useful. Colorectal Disease © 2014 The Association of Coloproctology of Great Britain and Ireland.

  20. Lifetime prevalence of cervical neoplasia in addicted and medical patients.

    PubMed

    Reece, Albert

    2007-10-01

    The prevalence and timing of cervical dysplasia among substance use disorder (SUD) patients is not well studied. A cross-sectional pilot survey was undertaken among our primary practice female medical and SUD patients by patient recall of cervical screening history. One hundred and fifty-three SUD patients were compared with 77 general medical patients younger than 45 years old. The substances abused in this population have previously been described. There was no difference in the mean number of Pap smears (mean +/- SEM 6.30 +/- 0.55 vs 5.68 +/- 0.70, respectively) or the time since last screening (2.93 +/- 0.29 vs 1.60 +/- 0.26 years). Limiting the analysis to patients younger than 45 years effectively controlled for the difference in ages between SUD and medical patients (29.94 +/- 0.52 and 30.21 +/- 1.04 years). Significant differences in cytological abnormalities (OR = 5.88, CI 1.92-23.92; P = 0.0005), cervical intraepithelial neoplasia (CIN) (OR = 14.4, CI 2.20-602.92, P = 0.001) and high-grade CIN-cancer (P = 0.002) were noted. When diagnoses were scored and charted, the trend of the lines of best fit in the two groups was significantly different (P < 0.00001). There were five and two cancers noted in the two groups. There were two and ten hysterectomies performed in the two groups which were for two and one indications of cancer, respectively. In the addicted group invasive cancer was diagnosed at 23-, 23-, 34- and 37-years olds. SUD patients have a very high rate of abnormalities on cervical screening including precancerous lesions and these changes occurred at significantly younger ages. The possibility of some form of cancer promotion merits further investigation.

  1. Association of multiple endocrine neoplasia type 2 and Hirschsprung disease.

    PubMed

    Romeo, G; Ceccherini, I; Celli, J; Priolo, M; Betsos, N; Bonardi, G; Seri, M; Yin, L; Lerone, M; Jasonni, V; Martucciello, G

    1998-06-01

    In a few patients with Hirschsprung disease (HSCR) and no clinical symptoms of multiple endocrine neoplasia type 2 (MEN-2A) or medullary thyroid carcinoma (MTC), missense mutations in the cysteine residues 609 and 620 of the Ret gene have been identified. In several pedigrees with either MEN-2A or familial MTC (FMTC) a documented germline mutation in cysteine 618 or 620 follows the segregation of the disease phenotype. The appearance of the HSCR phenotype in such patients and pedigrees cannot be easily reconciled with the gain of function which is associated with the dominant oncogenic effect of MEN-2A mutations. Gastrointestinal manifestations are known to occur also in association with MEN-2B but, to the best of our knowledge, in only very few cases the intestinal phenotype of MEN-2B has been investigated by enzymo-histochemical techniques, as in the present work. We report an extensive molecular study of patients, two with HSCR and FMTC carrying a Cys620Arg or Ser mutation and two with MEN-2B and gastrointestinal symptoms carrying a Met918Thr mutation. One of the latter two patients showed aganglionosis of the last 5 cm of rectum which caused a congenital megacolon leading to the diagnosis and operation for HSCR. The mutation screening of all the exons of Ret in 3 of these patients did not reveal any additional mutation. Therefore these results do not support the hypothesis of additional constitutional Ret mutations in patients showing association of MEN-2 and HSCR, whilst the histochemical and clinical data in one of these patients indicate that MEN-2B can be associated with a true form of short segment HSCR.

  2. MicroRNAs for Detection of Pancreatic Neoplasia

    PubMed Central

    Vila-Navarro, Elena; Vila-Casadesús, Maria; Moreira, Leticia; Duran-Sanchon, Saray; Sinha, Rupal; Ginés, Àngels; Fernández-Esparrach, Glòria; Miquel, Rosa; Cuatrecasas, Miriam; Castells, Antoni; Lozano, Juan José; Gironella, Meritxell

    2017-01-01

    Objective: The aim of our study was to analyze the miRNome of pancreatic ductal adenocarcinoma (PDAC) and its preneoplastic lesion intraductal papillary mucinous neoplasm (IPMN), to find new microRNA (miRNA)-based biomarkers for early detection of pancreatic neoplasia. Objective: Effective early detection methods for PDAC are needed. miRNAs are good biomarker candidates. Methods: Pancreatic tissues (n = 165) were obtained from patients with PDAC, IPMN, or from control individuals (C), from Hospital Clínic of Barcelona. Biomarker discovery was done using next-generation sequencing in a discovery set of 18 surgical samples (11 PDAC, 4 IPMN, 3 C). MiRNA validation was carried out by quantitative reverse transcriptase PCR in 2 different set of samples. Set 1—52 surgical samples (24 PDAC, 7 IPMN, 6 chronic pancreatitis, 15 C), and set 2—95 endoscopic ultrasound-guided fine-needle aspirations (60 PDAC, 9 IPMN, 26 C). Results: In all, 607 and 396 miRNAs were significantly deregulated in PDAC and IPMN versus C. Of them, 40 miRNAs commonly overexpressed in both PDAC and IPMN were selected for further validation. Among them, significant up-regulation of 31 and 30 miRNAs was confirmed by quantitative reverse transcriptase PCR in samples from set 1 and set 2, respectively. Conclusions: miRNome analysis shows that PDAC and IPMN have differential miRNA profiles with respect to C, with a large number of deregulated miRNAs shared by both neoplastic lesions. Indeed, we have identified and validated 30 miRNAs whose expression is significantly increased in PDAC and IPMN lesions. The feasibility of detecting these miRNAs in endoscopic ultrasound-guided fine-needle aspiration samples makes them good biomarker candidates for early detection of pancreatic cancer. PMID:27232245

  3. Subconjunctival bevacizumab injection for ocular surface squamous neoplasia.

    PubMed

    Faramarzi, Amir; Feizi, Sepehr

    2013-07-01

    To determine the efficacy and safety of perilesional/subconjunctival bevacizumab injections in the management of ocular surface squamous neoplasia (OSSN). Ten eyes of 10 patients with an OSSN diagnosis confirmed by impression cytology received 2 perilesional/subconjunctival injections of bevacizumab at a 2-week interval. Patients were evaluated for 3 months, during which time, changes in the lesions were documented using digital photography. After this period, excisional biopsy of the remaining tumor and cryotherapy of the conjunctival borders were performed if deemed necessary. The mean age of the patients was 65 ± 12 years (± SD). All of the tumors were nasal in origin and had varying degrees of vascularization. The mean lesion area before treatment was 16 ± 6.9 mm2. Two weeks after the first injection, the mean reduction observed in the tumor area was 25% ± 5.65% and ranged from 17% to 33% (P = 0.001). Two weeks after the second injection, the mean tumor area was further decreased (42% ± 33%, ranging from 15% to 100%, P = 0.049). Corneal extension of the tumor was not affected significantly in 8 of the eyes with concomitant conjunctival and corneal involvement. Complete disappearance of the tumor was demonstrated by impression cytology and occurred in 2 cases involving lesions clinically confined to the conjunctiva. No systemic or ocular side effects occurred during the study period. Perilesional/subconjunctival injections of bevacizumab decrease the size and vascularity of OSSN and may be curative in lesions limited to the conjunctiva. However, this treatment has no significant effect on the corneal extension of OSSN.

  4. Postmolar gestational trophoblastic neoplasia: beyond the traditional risk factors.

    PubMed

    Bakhtiyari, Mahmood; Mirzamoradi, Masoumeh; Kimyaiee, Parichehr; Aghaie, Abbas; Mansournia, Mohammd Ali; Ashrafi-Vand, Sepideh; Sarfjoo, Fatemeh Sadat

    2015-09-01

    To investigate the slope of linear regression of postevacuation serum hCG as an independent risk factor for postmolar gestational trophoblastic neoplasia (GTN). Multicenter retrospective cohort study. Academic referral health care centers. All subjects with confirmed hydatidiform mole and at least four measurements of β-hCG titer. None. Type and magnitude of the relationship between the slope of linear regression of β-hCG as a new risk factor and GTN using Bayesian logistic regression with penalized log-likelihood estimation. Among the high-risk and low-risk molar pregnancy cases, 11 (18.6%) and 19 cases (13.3%) had GTN, respectively. No significant relationship was found between the components of a high-risk pregnancy and GTN. The β-hCG return slope was higher in the spontaneous cure group. However, the initial level of this hormone in the first measurement was higher in the GTN group compared with in the spontaneous recovery group. The average time for diagnosing GTN in the high-risk molar pregnancy group was 2 weeks less than that of the low-risk molar pregnancy group. In addition to slope of linear regression of β-hCG (odds ratio [OR], 12.74, confidence interval [CI], 5.42-29.2), abortion history (OR, 2.53; 95% CI, 1.27-5.04) and large uterine height for gestational age (OR, 1.26; CI, 1.04-1.54) had the maximum effects on GTN outcome, respectively. The slope of linear regression of β-hCG was introduced as an independent risk factor, which could be used for clinical decision making based on records of β-hCG titer and subsequent prevention program. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  5. Molecular heterogeneity and prognostic implications of synchronous advanced colorectal neoplasia

    PubMed Central

    Malesci, A; Basso, G; Bianchi, P; Fini, L; Grizzi, F; Celesti, G; Di Caro, G; Delconte, G; Dattola, F; Repici, A; Roncalli, M; Montorsi, M; Laghi, L

    2014-01-01

    Background: It is uncertain whether synchronous colorectal cancers (S-CRCs) preferentially develop through widespread DNA methylation and whether they have a prognosis worse than solitary CRC. As tumours with microsatellite instability (MSI) may confound the effect of S-CRC methylation on outcome, we addressed this issue in a series of CRC characterised by BRAF and MS status. Methods: Demographics, clinicopathological records and disease-specific survival (DSS) were assessed in 881 consecutively resected CRC undergoing complete colonoscopy. All tumours were typed for BRAFc.1799T>A mutation and MS status, followed by search of germ-line mutation in patients with MSI CRC. Results: Synchronous colorectal cancers (50/881, 5.7%) were associated with stage IV microsatellite-stable (MSS) CRC (19/205, 9.3%, P=0.001) and with HNPCC (9/32, 28%, P<0.001). BRAF mutation (60/881, 6.8%) was associated with sporadic MSI CRC (37/62, 60%, P<0.001) but not with S-CRC (3/50, 6.0%, P=0.96). Synchronous colorectal cancer (HR 1.82; 95% CI 1.15–2.87; P=0.01), synchronous advanced adenoma (HR 1.81; 95% CI 1.27–2.58; P=0.001), and BRAFc.1799T>A mutation (HR 2.16; 95% CI 1.25–3.73; P=0.01) were stage-independent predictors of death from MSS CRC. Disease-specific survival of MSI CRC patients was not affected by S-CRC (HR 0.74; 95% CI 0.09–5.75; P=0.77). Conclusion: Microsatellite-stable CRCs have a worse prognosis if S-CRC or synchronous advanced adenoma are diagnosed. The occurrence and the enhanced aggressiveness of synchronous MSS advanced neoplasia are not associated with BRAF mutation. PMID:24434431

  6. 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

  7. Conditional deletion of ELL2 induces murine prostate intraepithelial neoplasia.

    PubMed

    Pascal, Laura E; Masoodi, Khalid Z; Liu, June; Qiu, Xiaonan; Song, Qiong; Wang, Yujuan; Zang, Yachen; Yang, Tiejun; Wang, Yao; Rigatti, Lora H; Chandran, Uma; Colli, Leandro M; Vencio, Ricardo Z N; Lu, Yi; Zhang, Jian; Wang, Zhou

    2017-11-01

    Elongation factor, RNA polymerase II, 2 (ELL2) is an RNA Pol II elongation factor with functional properties similar to ELL that can interact with the prostate tumor suppressor EAF2. In the prostate, ELL2 is an androgen response gene that is upregulated in benign prostatic hyperplasia (BPH). We recently showed that ELL2 loss could enhance prostate cancer cell proliferation and migration, and that ELL2 gene expression was downregulated in high Gleason score prostate cancer specimens. Here, prostate-specific deletion of ELL2 in a mouse model revealed a potential role for ELL2 as a prostate tumor suppressor in vivoEll2-knockout mice exhibited prostatic defects including increased epithelial proliferation, vascularity and PIN lesions similar to the previously determined prostate phenotype in Eaf2-knockout mice. Microarray analysis of prostates from Ell2-knockout and wild-type mice on a C57BL/6J background at age 3 months and qPCR validation at 17 months of age revealed a number of differentially expressed genes associated with proliferation, cellular motility and epithelial and neural differentiation. OncoPrint analysis identified combined downregulation or deletion in prostate adenocarcinoma cases from the Cancer Genome Atlas (TCGA) data portal. These results suggest that ELL2 and its pathway genes likely play an important role in the development and progression of prostate cancer. © 2017 Society for Endocrinology.

  8. Eosinophils promote epithelial to mesenchymal transition of bronchial epithelial cells.

    PubMed

    Yasukawa, Atsushi; Hosoki, Koa; Toda, Masaaki; Miyake, Yasushi; Matsushima, Yuki; Matsumoto, Takahiro; Boveda-Ruiz, Daniel; Gil-Bernabe, Paloma; Nagao, Mizuho; Sugimoto, Mayumi; Hiraguchi, Yukiko; Tokuda, Reiko; Naito, Masahiro; Takagi, Takehiro; D'Alessandro-Gabazza, Corina N; Suga, Shigeru; Kobayashi, Tetsu; Fujisawa, Takao; Taguchi, Osamu; Gabazza, Esteban C

    2013-01-01

    Eosinophilic inflammation and remodeling of the airways including subepithelial fibrosis and myofibroblast hyperplasia are characteristic pathological findings of bronchial asthma. Epithelial to mesenchymal transition (EMT) plays a critical role in airway remodelling. In this study, we hypothesized that infiltrating eosinophils promote airway remodelling in bronchial asthma. To demonstrate this hypothesis we evaluated the effect of eosinophils on EMT by in vitro and in vivo studies. EMT was assessed in mice that received intra-tracheal instillation of mouse bone marrow derived eosinophils and in human bronchial epithelial cells co-cultured with eosinophils freshly purified from healthy individuals or with eosinophilic leukemia cell lines. Intra-tracheal instillation of eosinophils was associated with enhanced bronchial inflammation and fibrosis and increased lung concentration of growth factors. Mice instilled with eosinophils pre-treated with transforming growth factor(TGF)-β1 siRNA had decreased bronchial wall fibrosis compared to controls. EMT was induced in bronchial epithelial cells co-cultured with human eosinophils and it was associated with increased expression of TGF-β1 and Smad3 phosphorylation in the bronchial epithelial cells. Treatment with anti-TGF-β1 antibody blocked EMT in bronchial epithelial cells. Eosinophils induced EMT in bronchial epithelial cells, suggesting their contribution to the pathogenesis of airway remodelling.

  9. High frequency of coexistence of columnar cell lesions, lobular neoplasia, and low grade ductal carcinoma in situ with invasive tubular carcinoma and invasive lobular carcinoma.

    PubMed

    Abdel-Fatah, Tarek M A; Powe, Desmond G; Hodi, Zsolt; Lee, Andrew H S; Reis-Filho, Jorge S; Ellis, Ian O

    2007-03-01

    This study was undertaken to determine the morphologic features and frequency of putative precursor lesions involved in the development of some pure forms of special types and low grade breast carcinoma. We reviewed 147 successive tumor cases, comprising tubular carcinoma (TC); pure type (n=56) and mixed type (n=20), invasive lobular carcinoma (ILC); classic type (n=57), and tubulolobular carcinoma (TLC; n=14). The presence of preinvasive lesions including columnar cell lesions (CCLs), usual epithelial hyperplasia, ductal carcinoma in situ (DCIS), and lobular neoplasia (LN) was determined. Estrogen receptor and E-cadherin immunohistochemistry was performed. Ninety-five percent (95%) of pure TCs had associated CCLs with the majority showing flat epithelial atypia. Atypical ductal hyperplasia (ADH)/DCIS was present in 89% patients. Colocalization of CCL, ADH/DCIS, and TC was seen in 85% patients, all displaying the same cytologic-nuclear morphology in most cases. LN was seen in 16%. In ILC, 91% cases showed LN. CCL and ADH/DCIS were seen in 60% and 42% cases, respectively. E-cadherin was positive in TLC but reduced in TC and completely absent in ILC. In conclusion, our findings support the hypothesis that CCLs are associated with pure and mixed forms of TC, and that LN is involved in ILC development. Our observations suggest that these lesions represent family members of low grade precursor, in situ and invasive neoplastic lesions of the breast. Molecular studies are being performed to substantiate the hypothesis that tubular and lobular carcinomas have direct evolutionary links to CCLs and flat epithelial atypia.

  10. Role of IAPs in prostate cancer progression: immunohistochemical study in normal and pathological (benign hyperplastic, prostatic intraepithelial neoplasia and cancer) human prostate

    PubMed Central

    2010-01-01

    Background In this study was investigate IAPs in normal human prostate (NP), benign prostatic hyperplasia (BPH), prostatic intraepithelial neoplasia (PIN) and prostatic carcinoma (PC), and their involvement in apoptosis/proliferation via NF-kB (TNF-α, IL-1) stimulation. Methods Immunohistochemical and Western blot analyses were performed in 10 samples of normal prostates, 35 samples of BPH, 27 samples diagnosis of PIN (with low-grade PIN or high-grade PIN) and 95 samples of PC (with low, medium or high Gleason grades). Results In NP, cytoplasm of epithelial cells were positive to c-IAP1/2 (80% of samples), c-IAP-2 (60%), ILP (20%), XIAP (20%); negative to NAIP and survivin. In BPH, epithelial cells were immunostained to c-IAP1/2 (57.57%), c-IAP-2 (57.57%), ILP (66.6%), NAIP (60.6%), XIAP (27.27%), survivin (9.1%). Whereas low-grade PIN showed intermediate results between NP and BPH; results in high-grade PIN were similar to those found in PC. In PC, epithelial cells were immunostained to c-IAP1/2, c-IAP-2, ILP, NAIP, XIAP (no Gleason variation) and survivin (increasing with Gleason). Conclusions IAPs could be involved in prostate disorder (BPH, PIN and PC) development since might be provoke inhibition of apoptosis and subsequently cell proliferation. At the same time, different transduction pathway such as IL-1/NIK/NF-kB or TNF/NF-kB (NIK or p38) also promotes proliferation. Inhibitions of IAPs, IL-1α and TNFα might be a possible target for PC treatment since IAPs are the proteins that inhibited apoptosis (favour proliferation) and IL-1α and TNFα would affect all the transduction pathway involucrate in the activation of transcription factors related to survival or proliferation (NF-kB, Elk-1 or ATF-2). PMID:20078866

  11. Integrins and epithelial cell polarity.

    PubMed

    Lee, Jessica L; Streuli, Charles H

    2014-08-01

    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.

  12. Lung Epithelial Progenitor Cells

    PubMed Central

    Rawlins, Emma L.

    2008-01-01

    The current enthusiasm for stem cell research stems from the hope that damaged or diseased tissues may one day be repaired through the manipulation of endogenous or exogenous stem cells. The postnatal human respiratory system is highly accessible and provides unique opportunities for the application of such techniques. Several putative adult lung epithelial stem cells have been identified in the mouse model system. However, their in vivo capabilities to contribute to different lineages, and their control mechanisms, remain unclear. If stem cell–based therapies are to be successful in the lung, it is vitally important that we understand the normal behavior of adult lung stem cells, and how this is regulated. Lung embryonic progenitor cells are much better defined and characterized than their adult counterparts. Moreover, experiments on a variety of developing tissues are beginning to uncover general mechanisms by which embryonic progenitors influence final organ size and structure. This provides a framework for the study of lung embryonic progenitor cells, facilitating experimental design and interpretation. A similar approach to investigating adult lung stem cells could produce rapid advances in the field. PMID:18684716

  13. Theory of epithelial elasticity

    NASA Astrophysics Data System (ADS)

    Krajnc, Matej; Ziherl, Primož

    2015-11-01

    We propose an elastic theory of epithelial monolayers based on a two-dimensional discrete model of dropletlike cells characterized by differential surface tensions of their apical, basal, and lateral sides. We show that the effective tissue bending modulus depends on the apicobasal differential tension and changes sign at the transition from the flat to the fold morphology. We discuss three mechanisms that stabilize the finite-wavelength fold structures: Physical constraint on cell geometry, hard-core interaction between non-neighboring cells, and bending elasticity of the basement membrane. We show that the thickness of the monolayer changes along the waveform and thus needs to be considered as a variable rather than a parameter. Next we show that the coupling between the curvature and the thickness is governed by the apicobasal polarity and that the amplitude of thickness modulation along the waveform is proportional to the apicobasal differential tension. This suggests that intracellular stresses can be measured indirectly by observing easily measurable morphometric parameters. We also study the mechanics of three-dimensional structures with cylindrical symmetry.

  14. 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

  15. 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.

  16. 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.

  17. Risk factors associated with Barrett’s epithelial dysplasia

    PubMed Central

    Fujita, Mikiko; Nakamura, Yuri; Kasashima, Saeko; Furukawa, Maiko; Misaka, Ryoichi; Nagahara, Hikaru

    2014-01-01

    AIM: To elucidate risk factors associated with dysplasia of short-segment Barrett’s esophagus (BE). METHODS: A total of 151 BE patients who underwent endoscopic examination from 2004 to 2008 in Aoyama Hospital, Tokyo Women’s Medical University, Japan and whose diagnosis was confirmed from biopsy specimens were enrolled in the study. BE was diagnosed based on endoscopic findings of gastric-appearing mucosa or apparent columnar-lined esophagus proximal to the esophagogastric junction. Dysplasia was classified into three grades - mild, moderate and severe - according to the guidelines of the Vienna Classification System for gastrointestinal epithelial neoplasia. Anthropometric and biochemical data were analyzed to identify risk factors for BE dysplasia. The prevalence of Helicobacter pylori (H. pylori) infection and the expression of p53 by immunohistological staining were also investigated. RESULTS: Histological examination classified patients into three types: specialized columnar epithelium (SCE) (n = 65); junctional (n = 38); and gastric fundic (n = 48). The incidence of dysplasia or adenocarcinoma from BE of the SCE type was significantly higher than that of the other two types (P < 0.01). The univariate analysis revealed that sex, H. pylori infection, body weight, p53 overexpression, and low diastolic blood pressure (BP) were associated with BE dysplasia. In contrast, body mass index, waist circumference, metabolic syndrome complications, and variables related to glucose or lipid metabolism were not associated with dysplasia. Multivariate logistic analysis showed that overexpression of p53 [odds ratio (OR) = 13.1, P = 0.004], H. pylori infection (OR = 0.19, P = 0.066), and diastolic BP (OR = 0.87, P = 0.021) were independent risk factors for epithelial dysplasia in BE patients with the SCE type. CONCLUSION: Overexpression of p53 is a risk factor for dysplasia of BE, however, H. pylori infection and diastolic BP inversely associated with BE dysplasia might be

  18. Parathyroid mitogenic activity in plasma from patients with familial multiple endocrine neoplasia type 1

    SciTech Connect

    Brandi, M.L.; Aurbach, G.D.; Fitzpatrick, L.A.; Quarto, R.; Spiegel, A.M.; Bliziotes, M.M.; Norton, J.A.; Doppman, J.L.; Marx, S.J.

    1986-05-15

    Hyperplasia of the parathyroid glands is a central feature of familial multiple endocrine neoplasia type 1. We used cultured bovine parathyroid cells to test for mitogenic activity in plasma from patients with this disorder. Normal plasma stimulated (/sup 3/H)thymidine incorporation, on the average, to the same extent as it was stimulated in a plasma-free control culture. This contrasted with the results of the tests with plasma from patients with familial multiple endocrine neoplasia type 1, in which parathyroid mitogenic activity increased 2400 percent over the control value (P less than 0.001). Plasma from these patients also stimulated the proliferation of bovine parathyroid cells in culture, whereas plasma from normal subjects inhibited it. Parathyroid mitogenic activity in plasma from the patients with familial multiple endocrine neoplasia type 1 was greater than that in plasma from patients with various other disorders, including sporadic primary hyperparathyroidism (with adenoma, hyperplasia, or cancer of the parathyroid), sporadic primary hypergastrinemia, sporadic pituitary tumor, familial hypocalciuric hypercalcemia, and multiple endocrine neoplasia type 2 (P less than 0.05). Parathyroid mitogenic activity in the plasma of patients with familial multiple endocrine neoplasia type 1 persisted for up to four years after total parathyroidectomy. The plasma also had far more mitogenic activity in cultures of parathyroid cells than did optimal concentrations of known growth factors or of any parathyroid secretagogue. This mitogenic activity had an apparent molecular weight of 50,000 to 55,000. We conclude that primary hyperparathyroidism in familial multiple endocrine neoplasia type 1 may have a humoral cause.

  19. Immunohistochemical localization of human papilloma virus in conjunctival neoplasias: A retrospective study

    PubMed Central

    Sharma, Anjana; Panda, Anita

    2007-01-01

    Background: The extent of association of human papilloma virus (HPV) in human conjunctival neoplasias has been debated in studies originating from different parts of the world, but no substantial evidence has been generated on Indian subjects. This prompted us to carry out a retrospective study on conjunctival neoplasias diagnosed over the past 12 years. Materials and Methods: Histopathological and immunohistochemical analysis of 65 specimens of ocular neoplasias and 30 normal controls diagnosed between 1991 and 2002 at a tertiary eye care hospital, was undertaken. Formalin-fixed, paraffin-embedded tissues were reviewed for confirming histopathological diagnosis, presence of koilocytosis and changes related to actinic keratosis. Immunohistochemical analysis was done using HPV-specific monoclonal antibodies. Clinicopathological correlation and the association of HPV antigen with the histopathological features were performed. Results: Out of the 65 cases analyzed, 35 were papillomas and 30 were ocular surface squamous neoplasias (OSSN). The mean age was 48 years with a male preponderance. Histologically, koilocytosis was observed in 17.1% of papillomas and 36.6% of OSSN. Actinic keratosis was present in 33% of OSSN. Immunohistochemically 17.1% conjunctival papillomas stained positive for HPV antigen, all cases of OSSN were negative for HPV. There was no correlation between koilocytosis or actinic keratosis and the detection of HPV antigen. Conclusions: The association between HPV and conjunctival neoplasias is variable in different geographical areas and also depends on the methods of detection used. This study warrants the need for applying more advanced techniques at a molecular level to determine the possible etiology of HPV in conjunctival neoplasias among Asian-Indians. PMID:17699945

  20. Sarcopenia is associated with an increased risk of advanced colorectal neoplasia.

    PubMed

    Park, Youn Su; Kim, Ji Won; Kim, Byeong Gwan; Lee, Kook Lae; Lee, Jae Kyung; Kim, Joo Sung; Koh, Seong-Joon

    2017-04-01

    Although sarcopenia is associated with an increased risk for mortality after the curative resection of colorectal cancer, its influence on the development of advanced colonic neoplasia remains unclear. This study included 1270 subjects aged 40 years or older evaluated with first-time screening colonoscopy at Seoul National University Boramae Health Care Center from January 2010 to February 2015. Skeletal muscle mass was measured with a body composition analyzer (direct segmental multifrequency bioelectrical impedance analysis method). Multiple logistic regression analysis was performed to determine whether sarcopenia is associated with advanced colorectal neoplasia. Of 1270 subjects, 139 (10.9%) were categorized into the sarcopenia group and 1131 (89.1%) into the non-sarcopenia group. In the non-sarcopenia group, 55 subjects (4.9%) had advanced colorectal neoplasia. However, in the sarcopenia group, 19 subjects (13.7%) had advanced colorectal neoplasia, including 1 subject with invasive colorectal cancer (0.7%). In addition, subjects with sarcopenia had a higher prevalence of advanced adenoma (P < 0.001) than those without sarcopenia. According to the multiple logistic regression analysis adjusted for variable confounders, age (odds ratio 1.062, 95% confidence interval 1.032-1.093; P < 0.001), male sex (odds ratio 1.749, 95% confidence interval 1.008-3.036; P = 0.047), and sarcopenia (odds ratio 2.347, 95% confidence interval 1.311-4.202; P = 0.004) were associated with an advanced colorectal neoplasia. Sarcopenia is associated with an increased risk of advanced colorectal neoplasia.

  1. High-resolution microendoscope for the detection of cervical neoplasia.

    PubMed

    Grant, Benjamin D; Schwarz, Richard A; Quang, Timothy; Schmeler, Kathleen M; Richards-Kortum, Rebecca

    2015-01-01

    Cervical cancer causes 275,000 deaths each year with 85 % of these deaths occurring in the developing world. One of the primary reasons for the concentration of deaths in developing countries is a lack of effective screening methods suited for the infrastructure of these countries. In order to address this need, we have developed a high-resolution microendoscope (HRME). The HRME is a fiber-based fluorescence microscope with subcellular resolution. Using the vital stain proflavine, we are able to image cell nuclei in vivo and evaluate metrics such as nuclear-to-cytoplasmic ratio, critical to identifying precancerous epithelial regions. In this chapter, we detail the materials and methods necessary to build this system from commercially available parts.

  2. Epidemiology of ocular surface squamous neoplasia in Africa.

    PubMed

    Gichuhi, Stephen; Sagoo, Mandeep S; Weiss, Helen A; Burton, Matthew J

    2013-12-01

    To describe the epidemiology and an aetiological model of ocular surface squamous neoplasia (OSSN) in Africa. Systematic and non-systematic review methods were used. Incidence was obtained from the International Agency for Research on Cancer. We searched PubMed, EMBASE, Web of Science and the reference lists of articles retrieved. Meta-analyses were conducted using a fixed-effects model for HIV and cigarette smoking and random effects for human papilloma virus (HPV). The incidence of OSSN is highest in the Southern Hemisphere (16° South), with the highest age-standardised rate (ASR) reported from Zimbabwe (3.4 and 3.0 cases/year/100 000 population for males and females, respectively). The mean ASR worldwide is 0.18 and 0.08 cases/year/100 000 among males and females, respectively. The risk increases with exposure to direct daylight (2-4 h, OR = 1.7, 95% CI: 1.2-2.4 and ≥5 h OR = 1.8, 95% CI: 1.1-3.1) and outdoor occupations (OR = 1.7, 95% CI: 1.1-2.6). Meta-analysis also shows a strong association with HIV (6 studies: OR = 6.17, 95% CI: 4.83-7.89) and HPV (7 studies: OR = 2.64, 95% CI: 1.27-5.49) but not cigarette smoking (2 studies: OR = 1.40, 95% CI: 0.94-2.09). The effect of atopy, xeroderma pigmentosa and vitamin A deficiency is unclear. Africa has the highest incidence of OSSN in the world, where males and females are equally affected, unlike other continents where male disease predominates. African women probably have increased risk due to their higher prevalence of HIV and HPV infections. As the survival of HIV-infected people increases, and given no evidence that anti-retroviral therapy (ART) reduces the risk of OSSN, the incidence of OSSN may increase in coming years. © 2013 John Wiley & Sons Ltd.

  3. Diagnosing Ocular Surface Squamous Neoplasia in East Africa

    PubMed Central

    Nguena, Marie B.; van den Tweel, Jan G.; Makupa, William; Hu, Victor H.; Weiss, Helen A.; Gichuhi, Stephen; Burton, Matthew J.

    2014-01-01

    Objective To examine the reliability of clinical examination and in vivo confocal microscopy (IVCM) in distinguishing ocular surface squamous neoplasia (OSSN) from benign conjunctival lesions. Design Case-control study. Participants Sixty individuals with conjunctival lesions (OSSN and benign) and 60 age-matched controls with normal conjunctiva presenting to Kilimanjaro Christian Medical Centre, Moshi, Tanzania. Methods Participants were examined and photographed, and IVCM was performed. Patients with conjunctival lesions were offered excisional biopsy with histopathology and a human immunodeficiency virus (HIV) test. The IVCM images were read masked to the clinical appearance and pathology results. Images were graded for several specific features and given an overall categorization (normal, benign, or malignant). A group of 8 ophthalmologists were shown photographs of conjunctival lesions and asked to independently classify as OSSN or benign. Main Outcome Measures Comparison of the histopathology diagnosis with the clinical and IVCM diagnosis. Results Fifty-two cases underwent excisional biopsy with histopathology; 34 were on the OSSN spectrum, 17 were benign, and 1 was lymphoma. The cases and controls had comparable demographic profiles. Human immunodeficiency syndrome infection was more common in OSSN compared with benign cases (58.8% vs. 5.6%; odds ratio, 24.3, 95% confidence interval [CI], 2.8–204; P = 0.003). Clinically, OSSN lesions more frequently exhibited feeder vessels and tended to have more leukoplakia and a gelatinous appearance. Overall, the ophthalmologists showed moderate agreement with the histology result (average kappa = 0.51; 95% CI, 0.36–0.64). The masked grading of IVCM images reliably distinguished normal conjunctiva. However, IVCM was unable to reliably distinguish between benign lesions and OSSN because of an overlap in their appearance (kappa = 0.44; 95% CI, 0.32–0.57). No single feature was significantly more frequent in OSSN

  4. Multiple endocrine neoplasia type 2A: a 25-year review.

    PubMed

    Iler, M A; King, D R; Ginn-Pease, M E; O'Dorisio, T M; Sotos, J F

    1999-01-01

    Before 1970, treatment decisions for the thyroid lesions in patients with multiple endocrine neoplasia (MEN) were based on physical findings. For the next 20 years, biological markers assumed a preeminent role, and at present, DNA testing is being used to define the need for therapeutic intervention. This report presents a 25-year review of 22 children with MEN-2A, with a mean follow-up of 12.5 years. All 22 children underwent a total thyroidectomy, and four (18%) were rendered permanently hypoparathyroid. Since 1976, however, only one patient (6.7%) has lost parathyroid function. Despite the fact that biological screening studies routinely were performed once a year in the majority of our patients and surgery was recommended for any elevation in the serum calcitonin (CT) levels, medullary carcinoma of the thyroid (MTC) developed in 17 children (77%) and only five had C cell hyperplasia (CCH). Thirteen of the 17 had macroscopic tumor described by the pathologist, evidence of recurrent disease (MTC-REC) has developed in four children (24%). There was considerable overlap in both the basal and stimulated CT levels among the five children with CCH, the 13 with localized MTC (MTC-NED), and the four who later had recurrent MTC. The basal calcitonin levels were between 25 and 110 (mean, 58) in the CCH patients, 30 to 1,130 (mean, 184) in the MTC-NED group, and 108 to 201 (mean, 140) in those with recurrent MTC. The corresponding stimulated calcitonin levels were 45 to 417 (mean, 179) in CCH, 111 to 9,510 (mean, 1,407) in MTC-NED, and 449 to 5,093 (mean, 3,383) in MTC-REC. (1) Basal and pentagastrin-stimulated CT levels did not reliably discriminate between CCH and MTC and should not be used to define the timing of thyroid surgery in children with MEN-2A. (2) Surgical therapy should be undertaken early in childhood on the basis of molecular genetic testing. (3) Postoperative complications are infrequent in the modern era.

  5. Risk of Advanced Neoplasia Using the National Cancer Institute's Colorectal Cancer Risk Assessment Tool.

    PubMed

    Imperiale, Thomas F; Yu, Menggang; Monahan, Patrick O; Stump, Timothy E; Tabbey, Rebeka; Glowinski, Elizabeth; Ransohoff, David F

    2017-01-01

    There is no validated, discriminating, and easy-to-apply tool for estimating risk of colorectal neoplasia. We studied whether the National Cancer Institute's (NCI's) Colorectal Cancer (CRC) Risk Assessment Tool, which estimates future CRC risk, could estimate current risk for advanced colorectal neoplasia among average-risk persons. This cross-sectional study involved individuals age 50 to 80 years undergoing first-time screening colonoscopy. We measured medical and family history, lifestyle information, and physical measures and calculated each person's future CRC risk using the NCI tool's logistic regression equation. We related quintiles of future CRC risk to the current risk of advanced neoplasia (sessile serrated polyp or tubular adenoma ≥ 1 cm, a polyp with villous histology or high-grade dysplasia, or CRC). All statistical tests were two-sided. For 4457 (98.5%) with complete data (mean age = 57.2 years, SD = 6.6 years, 51.7% women), advanced neoplasia prevalence was 8.26%. Based on quintiles of five-year estimated absolute CRC risk, current risks of advanced neoplasia were 2.1% (95% confidence interval [CI] = 1.3% to 3.3%), 4.8% (95% CI = 3.5% to 6.4%), 6.4% (95% CI = 4.9% to 8.2%), 10.0% (95% CI = 8.1% to 12.1%), and 17.6% (95% CI = 15.5% to 20.6%; P < .001). For quintiles of estimated 10-year CRC risk, corresponding current risks for advanced neoplasia were 2.2% (95% CI = 1.4% to 3.5%), 4.8% (95% CI = 3.5% to 6.4%), 6.5% (95% CI = 5.0% to 8.3%), 9.3% (95% CI = 7.5% to 11.4%), and 18.4% (95% CI = 15.9% to 21.1%; P < .001). Among persons with an estimated five-year CRC risk above the median, current risk for advanced neoplasia was 12.8%, compared with 3.7% among those below the median (relative risk = 3.4, 95 CI = 2.7 to 4.4). The NCI's Risk Assessment Tool, which estimates future CRC risk, may be used to estimate current risk for advanced neoplasia, making it potentially useful for tailoring and improving CRC

  6. Differential diagnosis of integumentary and mucous membrane lesions. Neoplasia or inflammation?

    PubMed

    Cooley, A J

    1990-09-01

    Lesions occurring on the skin and mucous membranes of domestic animals often present both diagnostic challenges and diagnostic confusion. One of the most common causes of confusion is inflammatory lesions that can be mistaken for neoplasia and vice versa. This confusion may emanate from intrinsic biologic variability, histopathologic interpretation, secondary alterations subsequent to inflammation or necrosis, or sampling errors and omission of pertinent information by the clinician. Some diagnostic problems associated with diagnoses of granulomatous inflammation, mesenchymal neoplasia, mast cell tumors, and squamous cell carcinomas are presented, and selected specific differential diagnoses associated with diagnostic problems are discussed.

  7. Etiology, pathogenesis and epizootiology of hematopoietic neoplasia in the soft-shell clam, Mya arenaria

    SciTech Connect

    Paquette, G.E.

    1992-01-01

    Studies on the etiology of hematopoietic neoplasia (HN) in soft-shell clams, Mya arenaria, have been inconclusive. Petroleum-derived hydrocarbons, polychlorinated-biphenyls and a virus have all been implicated as causative agents. The isolation of 100 nm virus-like particles from neoplastic clams proved conclusively that the causative agent is a retrovirus. The virus can induce a neoplasia in non-neoplastic clams and similar virus particles can be re-isolated and induce neoplasia. The activities of the RT are temperature dependent, found at 6[degrees]C, but not at 25[degrees]C and 37[degrees]C. The incidence rate for neoplasia in Narragansett Bay, Rhode Island was 7.7% and for combined other locations, 3.7% (26/699). HN was present in clams throughout the year at varying levels. The highest incidence occurred in October (11.5%); the lowest incidence in April (1.2%) and June (2.5%). The outcome of the disease depends on the water temperature and degree of severity of neoplasia in the clams. Death rate was greatest when water temperature was at 15[degrees]C (100%). High severity clams had the highest death rate (100%). Chronicity of persistent neoplasia occurred more at 10[degrees]C (19%) than at 6[degrees]C (15%) or 15[degrees]C (0%). Remission occurred only in low severity juvenile clams at either 6[degrees]C or 10[degrees]C. Neoplasia causes metabolic alteration in clams. Remission occurred only in low severity juvenile clams at either 6[degrees]C or 10[degrees]C. The time to remission was longer at 6[degrees]C than 10[degrees]C. Neoplasia causes metabolic alteration in clams. This shown by a significant increase in uric acid, asparatate transminase and triglycerides and a decrease in urea in the hemolymph. The cell membrane of neoplastic hemocytes also shows differences in their binding pattern to lectin than the normal hemocytes, indicating a change in cell surface glycoprotein probably induced by the retrovirus.

  8. Mitomycin C as an adjunct in the treatment of localised ocular surface squamous neoplasia

    PubMed Central

    Chen, C; Louis, D; Dodd, T; Muecke, J

    2004-01-01

    Aim: To report the outcome of topical mitomycin C (MMC) used as adjunctive treatment following primary excision of ocular surface squamous neoplasia (OSSN). Method: Prospective, non-comparative interventional case series of 27 primary OSSN lesions from 26 patients treated in a single ocular oncology centre over a 4 year period. Result: 27 cases of OSSN received a treatment regimen of surgical excision, followed by topical MMC. Mean follow up of 27 (SD 12) months (range 12–50, median 25 months) revealed zero recurrences. Conclusion: MMC treatment following surgical excision decreases the recurrence rate of primary ocular surface neoplasia and should be considered as adjunctive therapy in primary treatment. PMID:14693762

  9. Role of the human papilloma virus in the development of cervical intraepithelial neoplasia and malignancy

    PubMed Central

    Jastreboff, A; Cymet, T

    2002-01-01

    Human papilloma virus (HPV) is a public health problem as a sexually transmitted disease and as a critical factor in the pathogenesis of various cancers. The clinical manifestations, epidemiology, and virology that are critical to understanding the process of cervical dysplasia and neoplasia are reviewed. A discussion of the cervical transformation zone and the classification of cervical dysplasia and neoplasia leads into the importance of the Papanicolaou smear in prevention of potentially devastating sequelae of this virus. The role of the immune system in the progression of the disease and how it relates to vaccines, as well as treatment and prevention of HPV, are reviewed. PMID:11930025

  10. Computer-aided detection of early Barrett's neoplasia using volumetric laser endomicroscopy.

    PubMed

    Swager, Anne-Fré; van der Sommen, Fons; Klomp, Sander R; Zinger, Sveta; Meijer, Sybren L; Schoon, Erik J; Bergman, Jacques J G H M; de With, Peter H; Curvers, Wouter L

    2017-03-16

    Volumetric laser endomicroscopy (VLE) is an advanced imaging system that provides a near-microscopic resolution scan of the esophageal wall layers up to 3-mm deep. VLE has the potential to improve detection of early neoplasia in Barrett's esophagus (BE). However, interpretation of VLE images is complex because of the large amount of data that need to be interpreted in real time. The aim of this study was to investigate the feasibility of a computer algorithm to identify early BE neoplasia on ex vivo VLE images. We used 60 VLE images from a database of high-quality ex vivo VLE-histology correlations, obtained from BE patients ± neoplasia (30 nondysplastic BE [NDBE] and 30 high-grade dysplasia/early adenocarcinoma images). VLE features from a recently developed clinical VLE prediction score for BE neoplasia served as input for the algorithm: (1) higher VLE surface than subsurface signal and (2) lack of layering. With this input, novel clinically inspired algorithm features were developed, based on signal intensity statistics and grayscale correlations. For comparison, generic image analysis methods were examined for their performance to detect neoplasia. For classification of the images in the NDBE or neoplastic group, several machine learning methods were evaluated. Leave-1-out cross-validation was used for algorithm validation. Three novel clinically inspired algorithm features were developed. The feature "layering and signal decay statistics" showed the optimal performance compared with the other clinically features ("layering" and "signal intensity distribution") and generic image analyses methods, with an area under the receiver operating characteristic curve (AUC) of .95. Corresponding sensitivity and specificity were 90% and 93%, respectively. In addition, the algorithm showed a better performance than the clinical VLE prediction score (AUC .81). This is the first study in which a computer algorithm for BE neoplasia was developed based on VLE images with

  11. [Changes of structure and function of spleen macrophages induced by malignant neoplasia].

    PubMed

    Bakhishinian, M Z; Aznaurian, A V

    2004-01-01

    Spleen macrophages, as most active elements of the mononuclear phagocyte system, were studied using light and electron microscopy in experimental rats and mice with differenet types of malignant neoplasia, including chemically induced carcinogenesis, transplantable tumor growth and in leukosis. In chemically induced carcinogenesis macrophage phagocytic activity was reduced, morphologically, the cellular surface smoothing, cytoplasm organell reduction and nuclear pyknotic changes were found. In animals with transplanted tumors, high activity of spleen macrophages was detected. In animals with leukosis, macrophages are characterized by reduced phagocytic activity, smoothed cellular surface and a variable number of lysosomes. The results obtained support the concept of high reactivity of the cells of mononuclear phagocyte system in neoplasia.

  12. 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

  13. Diagnostic Accuracy of a Qualitative Fecal Immunochemical Test Varies With Location of Neoplasia But Not Number of Specimens.

    PubMed

    Wong, Martin C S; Ching, Jessica Y L; Chan, Victor C W; Lam, Thomas Y T; Shum, Jeffrey P; Luk, Arthur K C; Wong, Sunny S H; Ng, Siew C; Ng, Simon S M; Wu, Justin C Y; Chan, Francis K L; Sung, Joseph J Y

    2015-08-01

    We compared the accuracy of a qualitative fecal immunochemical test (FIT) in identifying patients with proximal vs distal advanced neoplasia and evaluated whether analysis of 2 specimens performed better than analysis of 1 specimen. Distal advanced neoplasia was defined as colorectal cancer (CRC), any colorectal adenoma ≥10 mm in diameter, high-grade dysplasia, or a lesion with villous or tubulovillous histologic characteristics in a location distal to the splenic flexure, including the descending colon, the rectosigmoid, and the rectum. We collected data from 5343 subjects (50-70 years old) who received 2 FITs (Hemosure; cutoff value, 10 μg hemoglobin/g feces) before colonoscopy in an invitational CRC screening program in Hong Kong from 2008 through 2012. We calculated the FIT's sensitivity, specificity, positive predictive value (PPV), and negative predictive value in detecting colorectal neoplasia. Of the participants, 13.6%, 12.2%, and 6.0% had distal, proximal, and synchronous distal or proximal neoplasia, respectively. Advanced neoplasia was detected in 291 subjects (5.4%); 22 (0.4%) had CRC. FIT detected distal advanced adenoma with 39.7% sensitivity (95% confidence interval [CI], 32.0%-48.0%) vs proximal advanced adenoma with 25.0% sensitivity (95% CI, 17.3%-34.6%; P = .014), distal advanced neoplasia with 40.0% sensitivity (95% CI, 32.5%-47.9%) vs proximal advanced neoplasia with 27.9% sensitivity (95% CI, 20.0%-37.4%; P = .039), and any distal adenoma ≥10 mm, irrespective of other lesion characteristics, with 39.5% sensitivity (95% CI, 31.0%-48.7%) vs. proximal adenoma with 25.3% sensitivity (95% CI, 16.5%-36.6%; P = .038). The specificity of FIT in detecting CRC was similar between the proximal and distal colon. FIT detected distal lesions with higher PPV than proximal lesions. One FIT detected advanced neoplasia with 31.8% sensitivity (95% CI, 25.9%-38.4%) and 92.4% specificity (95% CI, 91.6%-93.2%), whereas 2 FITs detected advanced neoplasia with

  14. Establishment and characterization of mouse mammary carcinoma cell lines expressing RET with a multiple endocrine neoplasia 2A mutation.

    PubMed

    Kawai, Kumi; Jijiwa, Mayumi; Shimono, Yohei; Kurokawa, Kei; Murakumo, Yoshiki; Ichihara, Masatoshi; Takahashi, Masahide

    2003-11-01

    We recently generated transgenic mice expressing the RET proto-oncogene with a multiple endocrine neoplasia type 2A mutation (RET-MEN2A). Mammary tumors with frequent lung metastasis were developed in 22% of female transgenic mice in a stochastic fashion. In the current study, we established two cell lines (named MKK-f and MKK-s) from mammary tumors developed in RET-MEN2A transgenic mice. MKK-f and MKK-s were derived from well-differentiated ductal carcinoma and sarcomatous spindle cell carcinoma, respectively. MKK-f cells show epithelial-like morphology with a doubling time of 19 h, and MKK-s cells show spindle-shaped morphology with a doubling time of 15 h. When inoculated in immunodeficient mice, both cell lines were tumorigenic, metastasized to the lung and displayed histological features similar to those of the primary tumors. They maintained a high level of RET expression and activation of signaling molecules downstream of RET. Consistent with the histological phenotype, expression of E-cadherin was almost undetectable in MKK-s cells, whereas its expression was very high in MKK-f cells. When the difference of gene expression between the two cell lines was analyzed using cDNA microarrays including approximately 900 genes/ESTs, a total of 21 up- or down-regulated (> 2.0-fold) genes were identified. Differentially regulated genes included thymosin beta-10, fibroblast growth factor receptor 4, aldo-keto reductase and caspase 6 genes, which are known to be associated with tumor development and progression. These results may reflect the profiles of the transcriptional changes associated with dedifferentiation or progression of mammary carcinomas developed in genetically engineered mice.

  15. Cervical intraepithelial neoplasia in pregnancy: Interference of pregnancy status with p16 and Ki-67 protein expression.

    PubMed

    Ciavattini, Andrea; Sopracordevole, Francesco; Di Giuseppe, Jacopo; Moriconi, Lorenzo; Lucarini, Guendalina; Mancioli, Francesca; Zizzi, Antonio; Goteri, Gaia

    2017-01-01

    To date, there are evidence-based guidelines available for cervical dysplasia diagnosed in pregnancy. Certain functional biomarkers have proven useful in the prediction of regressing and non-regressing cervical intraepithelial neoplasia (CIN) lesions in non-pregnant women. In the present study, Ki-67 and p16 immunostaining were evaluated in different grades of CIN lesions diagnosed in pregnant or non-pregnant women with the aim to identify any differences in order to better understand the behavior of CIN in pregnancy. The current retrospective case-control study included 17 pregnant patients that conceived naturally with first-time onset of CIN occurring at no later than 16 gestational weeks. The control group included 17 non-pregnant patients matched for age, parity and number of previous sexual partners. Exclusion criteria included previous cervical treatment, immunocompromised status, chronic hepatitis B and/or C and cigarette smoking. p16 and Ki-67 protein expression were respectively detected using the CINtec Histology kit and monoclonal antibodies against Ki-67. p16 and Ki-67 staining were analyzed using a classification system based on the distribution of positivity on a semi-quantitative three point-scale. p16 and Ki-67 immune reactivity correlated positively with the grade of epithelial dysplasia in the total cohort of pregnant and non-pregnant patients; expression increased linearly from CIN1 to CIN3. Furthermore, the association between p16 immunostaining and CIN grade was significant in non-pregnant patients but not in pregnant patients. In pregnant patients, positivity for Ki-67 was less intense than in non-pregnant patients. These results appear to suggest that pregnancy status interferes with the expression of cellular proteins involved in cell-cycle regulation and the carcinogenic process induced by high-risk human papilloma virus, exhibiting increased variability in their staining.

  16. 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.

  17. Lack of commensal flora in H. pylori-infected INS-GAS mice reduces gastritis and delays intraepithelial neoplasia

    PubMed Central

    Lofgren, Jennifer L.; Whary, Mark T.; Ge, Zhongming; Muthupalani, Sureshkumar; Taylor, Nancy S.; Mobley, Melissa; Potter, Amanda; Varro, Andrea; Eibach, Daniel; Suerbaum, Sebastian; Wang, Timothy C.; Fox, James G.

    2010-01-01

    Background & Aims Transgenic, insulin–gastrin (INS–GAS) mice have high circulating levels of gastrin. On a FVB/N background, these mice develop spontaneous atrophic gastritis and gastrointestinal intraepithelial neoplasia (GIN) with 80% prevalence 6 months after Helicobacter pylori infection. GIN is associated with gastric atrophy and achlorhydria, predisposing mice to non-helicobacter microbiota overgrowth. We determined if germ-free INS–GAS mice spontaneously develop GIN and if H. pylori accelerates GIN in gnotobiotic INS–GAS mice. Methods We compared gastric lesions and levels of mRNA, serum inflammatory mediators, antibodies, and gastrin among germ-free and H. pylori-monoinfected INS-GAS mice. Microbiota composition of specific pathogen-free (SPF) INS-GAS mice was quantified by pyro-sequencing. Results Germ-free INS-GAS mice had mild hypergastrinemia but did not develop significant gastric lesions until they were 9 months old; they did not develop GIN through 13 months. H. pylori monoassociation caused progressive gastritis, epithelial defects, oxyntic gland atrophy, marked foveolar hyperplasia and dysplasia, and strong serum and tissue proinflammatory immune responses (particularly in male mice) between 5 and 11 months post infection (P<0.05, compared with germ-free controls). Only 2 of 26 female, whereas 8 of 18 male, H. pylori-infected INS-GAS mice developed low- to high-grade GIN by 11 months post infection. Stomachs of H. pylori-infected SPF male mice had significant reductions in Bacteroidetes and significant increases in Firmicutes. Conclusions Gastric lesions take 13 months longer to develop in germ-free INS–GAS mice than male SPF INS-GAS mice. H. pylori-monoassociation accelerated gastritis and GIN but caused less-severe gastric lesions and delayed onset of GIN compared to H. pylori-infected INS-GAS mice with complex gastric microbiota. Changes of gastric microbiota composition might promote GIN in the achlorhydric stomachs of SPF mice. PMID

  18. Cervical intraepithelial neoplasia in pregnancy: Interference of pregnancy status with p16 and Ki-67 protein expression

    PubMed Central

    Ciavattini, Andrea; Sopracordevole, Francesco; Di Giuseppe, Jacopo; Moriconi, Lorenzo; Lucarini, Guendalina; Mancioli, Francesca; Zizzi, Antonio; Goteri, Gaia

    2017-01-01

    To date, there are evidence-based guidelines available for cervical dysplasia diagnosed in pregnancy. Certain functional biomarkers have proven useful in the prediction of regressing and non-regressing cervical intraepithelial neoplasia (CIN) lesions in non-pregnant women. In the present study, Ki-67 and p16 immunostaining were evaluated in different grades of CIN lesions diagnosed in pregnant or non-pregnant women with the aim to identify any differences in order to better understand the behavior of CIN in pregnancy. The current retrospective case-control study included 17 pregnant patients that conceived naturally with first-time onset of CIN occurring at no later than 16 gestational weeks. The control group included 17 non-pregnant patients matched for age, parity and number of previous sexual partners. Exclusion criteria included previous cervical treatment, immunocompromised status, chronic hepatitis B and/or C and cigarette smoking. p16 and Ki-67 protein expression were respectively detected using the CINtec Histology kit and monoclonal antibodies against Ki-67. p16 and Ki-67 staining were analyzed using a classification system based on the distribution of positivity on a semi-quantitative three point-scale. p16 and Ki-67 immune reactivity correlated positively with the grade of epithelial dysplasia in the total cohort of pregnant and non-pregnant patients; expression increased linearly from CIN1 to CIN3. Furthermore, the association between p16 immunostaining and CIN grade was significant in non-pregnant patients but not in pregnant patients. In pregnant patients, positivity for Ki-67 was less intense than in non-pregnant patients. These results appear to suggest that pregnancy status interferes with the expression of cellular proteins involved in cell-cycle regulation and the carcinogenic process induced by high-risk human papilloma virus, exhibiting increased variability in their staining. PMID:28123559

  19. The EGF receptor family--multiple roles in proliferation, differentiation, and neoplasia with an emphasis on HER4.

    PubMed Central

    Earp, H. Shelton; Calvo, Benjamin F.; Sartor, Carolyn I.

    2003-01-01

    The EGF Receptor (EGFR), the first transmembrane receptor tyrosine kinase cloned and sequenced, and its closely related family members HER2, HER3, and HER4, play myriad roles in mammalian growth and development. Receptor activation involves ligand binding to separate receptors followed by formation of active dimers. These receptors can signal as homodimers or they can subtly alter signaling output by heterodimerizing with other family members. Adding complexity, these receptors with varying specificity bind at least 10 ligands from two ligand families, the EGF and neuregulin/heregulin families. This signaling system's impact on human neoplasia is underscored by the following: i.) EGFR is overexpressed or activated by autocrine or paracrine growth factor loops in at least 50% of epithelial malignancies; ii.) HER2 is amplified and dramatically overexpressed in approximately 20%-25% or breast cancers; iii) HER3 and HER4 are variably expressed in breast and other cancers. Overexpression and/or activation of EGFR, HER2 and HER3 has been correlated with poor tumor prognosis; antibody and small molecule inhibitors of their activity are being tested as therapy in cancer patients. However, the signaling complexity engendered by four interacting receptors and ten ligands makes it difficult to definitively measure receptor signaling output in human tumors and even makes mechanistic studies of the family's role in normal physiology and neoplastic transformation a challenge. In spite of the literature's emphasis on growth control, activation by some EGF receptor family member ligands can produce tumor cell differentiation, characterized by growth cessation and differentiation gene product synthesis. The present work delineates a role for HER4 in breast cancer cell differentiation and demonstrates that HER4 is both necessary and sufficient to produce an anti-proliferative signal. These Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 PMID:12813928

  20. Front-to-back & dabbing wiping behaviour post-toilet associated with anal neoplasia & HR-HPV carriage in women with previous HPV-mediated gynaecological neoplasia.

    PubMed

    Simpson, Steve; Blomfield, Penny; Cornall, Alyssa; Tabrizi, Sepehr N; Blizzard, Leigh; Turner, Richard

    2016-06-01

    Anal cancer is a human papillomavirus (HPV)-mediated neoplasia of the anal squamous epithelium. Anal cancer is much more common among women, particularly those with a previous high-grade gynaecological neoplasia. Cross-sectional study of women with a previous HPV-mediated gynaecological neoplasia in Tasmania, Australia. Women presenting for follow-up gynaecological care had anal swab samples taken for anal cytology by Hologic Liquid ThinPrep, followed by HPV genotyping. Women with abnormal anal cytology were invited for high-resolution anoscopy. Potential risk factors, including post-toilet wiping behaviours, were queried by questionnaire while clinical covariates were extracted from medical records. Covariates of anal outcomes evaluated by log-binomial and log-multinomial regression. From 163 women enrolled in the study, 65 (39.9%) had abnormal cytology, with 46 (28.2%) being high-grade. Of the 50 women with abnormal anal cytology having high-resolution anoscopy, 32 (64.0%) had abnormal histology with 13 (26.0%) being high-grade. Of the 123 women tested for HR-HPV DNA, 48 (39.0%) had HR-HPV detected, the most common genotypes being 16 and 51 (14/123, 11.4% for both). In addition to some known anal cancer risk factors, we found front-to-back wiping was associated with significantly increased (Prevalence ratio (PR) range: 1.99-3.60) prevalence of cytological and histological abnormality and HR-HPV carriage/co-carriage, while dabbing post-toilet was significantly associated with decreased prevalences (PR range: 0.50-0.62). Post-toilet wiping behaviours were significantly associated with the prevalence of anal cytological, histological and HR-HPV carriage outcomes. This suggests a biologically plausible mechanism for HR-HPV introduction and the higher frequencies of anal neoplasia in women. Copyright © 2016. Published by Elsevier Ltd.

  1. Inducible FGFR-1 activation leads to irreversible prostate adenocarcinoma and an epithelial-to-mesenchymal transition.

    PubMed

    Acevedo, Victor D; Gangula, Rama D; Freeman, Kevin W; Li, Rile; Zhang, Youngyou; Wang, Fen; Ayala, Gustavo E; Peterson, Leif E; Ittmann, Michael; Spencer, David M

    2007-12-01

    Fibroblast Growth Factor Receptor-1 (FGFR1) is commonly overexpressed in advanced prostate cancer (PCa). To investigate causality, we utilized an inducible FGFR1 (iFGFR1) prostate mouse model. Activation of iFGFR1 with chemical inducers of dimerization (CID) led to highly synchronous, step-wise progression to adenocarcinoma that is linked to an epithelial-to-mesenchymal transition (EMT). iFGFR1 inactivation by CID withdrawal led to full reversion of prostatic intraepithelial neoplasia, whereas PCa lesions became iFGFR1-independent. Gene expression profiling at distinct stages of tumor progression revealed an increase in EMT-associated Sox9 and changes in the Wnt signaling pathway, including Fzd4, which was validated in human PCa. The iFGFR1 model clearly implicates FGFR1 in PCa progression and demonstrates how CID-inducible models can help evaluate candidate molecules in tumor progression and maintenance.

  2. 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

  3. 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.

  4. Risk factors associated with diagnostic discrepancy of gastric indefinite neoplasia: Who need en bloc resection?

    PubMed

    Goo, Ja Jun; Choi, Cheol Woong; Kang, Dae Hwan; Kim, Hyung Wook; Park, Su Bum; Cho, Mong; Hwang, Sun Hwi; Lee, Si Hak

    2015-12-01

    Endoscopic forceps biopsy is insufficient for a definitive diagnosis of dysplastic lesions. It is difficult to decide clinical management of gastric indefinite neoplasia diagnosed by endoscopic forceps biopsy when early gastric cancer (EGC) is macroscopically suspected. The aim of this study was to discuss the final results of gastric indefinite neoplasia and associated clinical factors predictive of early gastric cancer. The medical records of 119 patients who were diagnosed with gastric indefinite neoplasia by index forceps biopsy were retrospectively reviewed. The initial endoscopic findings were analyzed, and predictive factors of EGC were evaluated. The final pathologic diagnoses of 119 patients included early gastric cancer (n = 26, 21.8%), adenoma (n = 6, 5.0%) and non-neoplasm (n = 87, 73.1%). Univariate analysis showed that lesion size greater than 10 mm, surface nodularity and surface redness were associated risk factors. In the multivariate analysis, lesions diameter (p = 0.021, OR 11.401, 95% CI 1.432-90.759) and surface redness (p = 0.014, OR 3.777, 95% CI 1.306-10.923) were significant risk factors. Patients with gastric indefinite neoplasia with larger size (≥10 mm) and surface redness might need further diagnostic investigation rather than simple follow-up endoscopy.

  5. 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.

  6. 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.

  7. Prevalence of colorectal neoplasia among young African Americans and Hispanic Americans.

    PubMed

    Ashktorab, Hassan; Paydar, Mansour; Namin, Hassan Hassanzadeh; Sanderson, Andrew; Begum, Rehana; Brim, Hassan; Panchal, Heena; Lee, Edward; Kibreab, Angesom; Nouraie, Mehdi; Laiyemo, Adeyinka O

    2014-02-01

    The disproportionately higher incidence of and mortality from colorectal cancer (CRC) among African Americans (AA) led the American College of Gastroenterology to recommend screening starting at age 45 in 2005. The purpose of this study was to determine the prevalence of colorectal neoplasia among 40-49-year-old inner city AA and Hispanic Americans (HA). We reviewed the medical records of 2,435 inner city AA and HA who underwent colonoscopy regardless of indication and compared the prevalence of colorectal neoplasia between AA and HA patients. We used logistic regression models to calculate odds ratios (OR) and 95 % confidence intervals (CI). There were 2,163 AAs and 272 HA. There were 57 % women in both groups. A total of 158 (7 %) AA and 9 (3 %) HA (P = 0.014) underwent the procedures for CRC screening. When compared to HAs, AAs had higher prevalence of any polyp (35 vs. 18 %, OR = 2.53; 95 % CI 1.82-3.52). Overall, AA had higher prevalence of colorectal neoplasia (adenoma and cancer) when compared to HAs (16 vs. 10 %; OR = 1.68; 95 % CI 1.10-2.56). We observed a higher frequency of colorectal neoplasia among 40-49-year-old AAs as compared to HAs suggesting an increased susceptibility to CRC risk in this population.

  8. Prevalence of colorectal neoplasia among young African Americans and Hispanic Americans

    PubMed Central

    Ashktorab, Hassan; Paydar, Mansour; Namin, Hassan Hassanzadeh; Sanderson, Andrew; Begum, Rehana; Brim, Hassan; Panchal, Heena; Lee, Edward; Kibreab, Angesom; Nouraie, Mehdi; Laiyemo, Adeyinka O.

    2014-01-01

    Background The disproportionately higher incidence of, and mortality from colorectal cancer (CRC) among African Americans (AA) led the American College of Gastroenterology to recommend screening starting at age 45 in 2005. Aim To determine the prevalence of colorectal neoplasia among 40–49 years old inner city African Americans (AA) and Hispanic Americans (HA). Methods We reviewed the medical records of 2435 inner city AA and HA who underwent colonoscopy regardless of indication and compared the prevalence of colorectal neoplasia between AA and HA patients. We used logistic regression models to calculate odds ratios (OR) and 95% confidence intervals (CI). Results There were 2,163 AA and 272 HA. There were 57% women in both groups. A total of 158 (7%) AA and 9 (3%) HA (P = 0.014) underwent the procedures for CRC screening. When compared to HA, AA had higher prevalence of any polyp (35% versus 18%, OR = 2.53; 95% CI: 1.82–3.52). Overall, AA had higher prevalence of colorectal neoplasia (adenoma and cancer) when compared to HA (16% versus 10%; OR = 1.68; 95% CI: 1.10–2.56). Conclusion We observed a higher frequency of colorectal neoplasia among 40–49 year-old AA as compared to HA suggesting an increased susceptibility to CRC risk in this population. PMID:24193352

  9. Studies on the presence of viral antibodies in patients with various forms of malignant neoplasia.

    PubMed

    Stoian, M; Hozoc, M; Ionescu, T; Lungu, M; Predescu, E; Nastac, E

    1975-01-01

    The study of viral antibodies in 6714 sera demonstrated that the level of antibodies to infectious viruses was the same in cancer patients as in controls. However, the patients with various forms of neoplasia showed a considerable percentage and high antibody levels to viruses with oncogenic potential for animals (adenovirus, SV40, Rous virus) or involved in human carcinogenesis (herpes virus).

  10. Multiple head and neck neoplasia following radiation for benign disease during childhood

    SciTech Connect

    Sirota, D.K.; Eden, A.R.; Biller, H.F.

    1988-06-01

    A woman received radiation therapy to the adenoids for benign disease at the age of 10 years and subsequently developed an adenocarcinoma of the middle ear, a parathyroid adenoma, and a papillary carcinoma of the thyroid gland in adulthood. This appears to be the first such case on record. The literature of neoplasia after head and neck irradiation is briefly reviewed.

  11. 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.

  12. Surveillance using trimodal imaging endoscopy after endoscopic submucosal dissection for superficial gastric neoplasia

    PubMed Central

    Imaeda, Hiroyuki; Hosoe, Naoki; Kashiwagi, Kazuhiro; Ida, Yosuke; Nakamura, Rieko; Suzuki, Hidekazu; Saito, Yoshimasa; Yahagi, Naohisa; Iwao, Yasushi; Kitagawa, Yuko; Hibi, Toshifumi; Ogata, Haruhiko; Kanai, Takanori

    2014-01-01

    AIM: To evaluate the effectiveness of trimodal imaging endoscopy (TME) to detect another lesion after endoscopic submucosal dissection (ESD) for superficial gastric neoplasia (SGN). METHODS: Surveillance esophagogastroduodenoscopy (EGD) using a TME was conducted in 182 patients that had undergone ESD for SGN. Autofluorescence imaging (AFI) was conducted after white-light imaging (WLI). When SGN was suspicious, magnifying endoscopy with narrow-band imaging (ME-NBI) was conducted. Final diagnoses were made by histopathologic findings of biopsy specimens. The detection rates of lesions in WLI, AFI, and NBI, and the characteristics of lesions detected by WLI and ones missed by WLI but detected by AFI were examined. The sensitivity, specificity, and accuracy of endoscopic diagnosis using WLI, AFI and ME-NBI were evaluated. RESULTS: In 242 surveillance EGDs, 27 lesions were determined pathologically to be neoplasias. Sixteen early gastric cancers and 6 gastric adenomas could be detected by WLI. Sixteen lesions were reddish and 6 were whitish. Five gastric neoplasias were missed by WLI but were detected by AFI, and all were whitish and protruded gastric adenomas. There was a significant difference in color and pathology between the two groups (P = 0.006). Sensitivity, specificity and accuracy in ME-NBI were higher than those in both WLI and AFI. Specificity and accuracy in AFI were lower than those in WLI. CONCLUSION: Surveillance using trimodal imaging endoscopy might be useful for detecting another lesion after endoscopic submucosal dissection for superficial gastric neoplasia. PMID:25473189

  13. Is microsatellite instability (MSI) associated with multiplicity in early stage gastric neoplasias?

    PubMed

    Park, Hong Jun; Kim, Hyun-Soo; Kim, Jae Woo; Park, So Yeun; Kim, Bo Ra; Ryu, Ho Yoel; Lee, Il Young; Lee, Yong Kwan; Cho, Mee Yon

    2013-09-01

    The aim of this study was to investigate the relationship between microsatellite instability (MSI) and clinicopathologic features including multiplicity in early stage gastric neoplasias (ESGN). From November 2004 until September 2009, 372 patients with consecutive resected gastric neoplasias were retrospectively enrolled. The gastric neoplasias were composed of 117 advanced gastric cancers (AGCs) and 255 ESGNs including 31 gastric dysplasias (including low and high grade dysplasia) and 224 early gastric cancers (EGCs). Based on microsatellite markers, high MSI (MSI-H) was observed in 61 cases (16.4%) and low MSI (MSI-L) in 14 cases (3.8%) of 372 cases. There was a positive correlation between the presence of MSI-H and progression of gastric adenoma to gastric tumor. We compared ESGNs with microsatellite stable (MSS; 223 cases, 87.5%) and ESGNs with MSI-H (24 cases, 9.4%). The ESGNs with MSI-H were only associated with older age and female gender. There were no association with Helicobacter pylori infection, intestinal metaplasia, and distal location in contrast with EGCs with MSI-H. Furthermore, multiplicity of ESGNs was not associated with MSI status. The clinicopatholgic features of MSI-H phenotype were different according to the progression of gastric neoplasias from ESGNs to AGCs. ESGNs with MSI-H were only associated with old age, female sex. In addition ESGNs with MSI-H were not associated with an increased risk of multifocal tumors. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  14. Complications of mitomycin C therapy in 100 eyes with ocular surface neoplasia

    PubMed Central

    Khong, J J; Muecke, J

    2006-01-01

    Aim To determine the complications associated with mitomycin C (MMC) in the treatment of ocular surface neoplasia. Methods A retrospective and consecutive study of 100 eyes in 91 patients with ocular surface neoplasia treated with MMC in a single centre between November 1998 and January 2005. Outcome measures included complications of MMC and the treatment required for these complications. Results One to three 7 day cycles of topical MMC 0.04% four times a day were given to 59 eyes with localised corneal‐conjunctival intraepithelial neoplasia (CIN), 19 eyes with diffuse CIN, six eyes with recurrent CIN, one eye with ocular surface squamous cell carcinoma, three eyes with primary acquired melanosis (PAM) with atypia, nine eyes with conjunctival malignant melanoma (MM), two eyes with sebaceous carcinoma with pagetoid spread, and one eye with recurrent atypical fibroxanthoma. Nine patients had bilateral CIN. 31 (34%) cases developed an allergic reaction to MMC and 14 (14%) eyes had epiphora secondary to punctal stenosis at a mean follow up period of 26.5 months. Conclusion In the largest study looking at complications of topical MMC in the treatment of ocular surface neoplasia, allergic reaction and punctal stenosis are relatively common. Serious complications were not observed suggesting the safe use of MMC in mid‐term follow up. PMID:16672325

  15. Lobular neoplasia diagnosed on breast Core biopsy: frequency of carcinoma on excision and implications for management.

    PubMed

    Calhoun, Benjamin C; Collie, Angela M B; Lott-Limbach, Abberly A; Udoji, Esther N; Sieck, Leah R; Booth, Christine N; Downs-Kelly, Erinn

    2016-12-01

    The appropriate follow-up and treatment for patients with a core biopsy diagnosis of lobular neoplasia (atypical lobular hyperplasia or lobular carcinoma in situ) remains controversial. Several studies have attempted to address this issue, with recommendations ranging from close clinical follow-up or surveillance to mandatory surgical excision in all cases. We report the findings at our institution, where virtually every core needle biopsy diagnosis of lobular neoplasia results in follow-up excision. The goal of the study was to identify potential predictors of upgrade to a more significant lesion. We identified 76 patients over a 15-year period with a core biopsy diagnosis of pure lobular neoplasia and no other high-risk lesions. Subsequent surgical excision identified 10 cases (13%) that were upgraded to carcinoma. Upgrade diagnoses included invasive ductal carcinoma (n=1), invasive lobular carcinoma (n=4), ductal carcinoma in situ (n=3), and pleomorphic lobular carcinoma in situ (n=2). All 10 upgraded cases had imaging findings suspicious for malignancy including irregular masses, asymmetric densities, or pleomorphic calcifications. Of the 10 upgraded cases, 7 were diagnosed as lobular carcinoma in situ on core biopsy. The data support a role for radiologic-pathologic correlation in the evaluation of suspicious breast lesions and suggest that the extent of lobular neoplasia in core biopsy specimens may be an indicator of the likelihood of upgrade to carcinoma.

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

    USDA-ARS?s Scientific Manuscript database

    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...

  17. 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...

  18. Image-guided stereotactic radiotherapy in 4 dogs with intracranial neoplasia.

    PubMed

    Moon, Alaina Burkard; Heller, Heidi Barnes; Forrest, Lisa

    2016-05-01

    The purpose of this study was to describe the use, and side effects, of a novel stereotactic radiotherapy protocol using TomoTherapy(®) in 4 dogs with confirmed or suspected primary extra-axial intracranial neoplasia. Three fractions of 8 Gy were prescribed. Acute side effects were noted in 1 dog; no late effects were noted.

  19. 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...

  20. 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.

  1. Condom use in prevention of Human Papillomavirus infections and cervical neoplasia: systematic review of longitudinal studies.

    PubMed

    Lam, Janni Uyen Hoa; Rebolj, Matejka; Dugué, Pierre-Antoine; Bonde, Jesper; von Euler-Chelpin, My; Lynge, Elsebeth

    2014-03-01

    Based on cross-sectional studies, the data on protection from Human Papillomavirus (HPV) infections related to using male condoms appear inconsistent. Longitudinal studies are more informative for this purpose. We undertook a systematic review of longitudinal studies on the effectiveness of male condoms in preventing HPV infection and cervical neoplasia. We searched PubMed using MeSH terms for articles published until May 2013. Articles were included if they studied a change in non-immunocompromized women's cervical HPV infection or cervical lesion status along with the frequency of condom use. In total, 384 abstracts were retrieved. Eight studies reported in 10 articles met the inclusion criteria for the final review. Four studies showed a statistically significantly protective effect of consistent condom use on HPV infection and on regression of cervical neoplasia. In the remaining four studies, a protective effect was also observed for these outcomes, although it was not statistically significant. Consistent condom use appears to offer a relatively good protection from HPV infections and associated cervical neoplasia. Advice to use condoms might be used as an additional instrument to prevent unnecessary colposcopies and neoplasia treatments in cervical screening, and to reduce the risk of cervical cancer.

  2. 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

  3. Intratubular germ cell neoplasia of the human testis: heterogeneous protein expression and relation to invasive potential.

    PubMed

    Mitchell, Rod T; E Camacho-Moll, Maria; Macdonald, Joni; Anderson, Richard A; Kelnar, Christopher J H; O'Donnell, Marie; Sharpe, Richard M; Smith, Lee B; Grigor, Ken M; Wallace, W Hamish B; Stoop, Hans; Wolffenbuttel, Katja P; Donat, Roland; Saunders, Philippa Tk; Looijenga, Leendert Hj

    2014-09-01

    Testicular germ cell cancer develops from premalignant intratubular germ cell neoplasia, unclassified cells that are believed to arise from failure of normal maturation of fetal germ cells from gonocytes (OCT4(+)/MAGEA4(-)) into pre-spermatogonia (OCT4(-)/MAGEA4(+)). Intratubular germ cell neoplasia cell subpopulations based on stage of germ cell differentiation have been described, however the importance of these subpopulations in terms of invasive potential has not been reported. We hypothesized that cells expressing an immature (OCT4(+)/MAGEA4(-)) germ cell profile would exhibit an increased proliferation rate compared with those with a mature profile (OCT4(+)/MAGEA4(+)). Therefore, we performed triple immunofluorescence and stereology to quantify the different intratubular germ cell neoplasia cell subpopulations, based on expression of germ cell (OCT4, PLAP, AP2γ, MAGEA4, VASA) and proliferation (Ki67) markers, in testis sections from patients with preinvasive disease, seminoma, and non-seminoma. We compared these subpopulations with normal human fetal testis and with seminoma cells. Heterogeneity of protein expression was demonstrated in intratubular germ cell neoplasia cells with respect to gonocyte and spermatogonial markers. It included an embryonic/fetal germ cell subpopulation lacking expression of the definitive intratubular germ cell neoplasia marker OCT4, that did not correspond to a physiological (fetal) germ cell subpopulation. OCT4(+)/MAGEA4(-) cells showed a significantly increased rate of proliferation compared with the OCT4(+)/MAGEA4(+) population (12.8 versus 3.4%, P<0.0001) irrespective of histological tumor type, reflected in the predominance of OCT4(+)/MAGEA4(-) cells in the invasive tumor component. Surprisingly, OCT4(+)/MAGEA4(-) cells in patients with preinvasive disease showed significantly higher proliferation compared to those with seminoma or non-seminoma (18.1 versus 10.2 versus 7.2%, P<0.05, respectively). In conclusion, this study

  4. Aflibercept in epithelial ovarian carcinoma

    PubMed Central

    Moroney, John W; Sood, Anil K; Coleman, Robert L

    2009-01-01

    Angiogenesis is a hallmark of malignant transformation. With improved understanding of angiogenic signaling in both the normal and malignant state, there have been a number of agents developed that target VEGF signaling. These targeted agents can affect downstream VEGF signal transduction via unique mechanisms at different cellular and extracellular locations. The aflibercept, or VEGF-Trap, molecule is the subject of this article. Its molecular structure, pharmacokinetic and pharmacodynamic profile, and preclinical and early clinical data in epithelial ovarian carcinoma is reviewed. For comparison, other anti-angiogenic agents that have been or are currently being studied in epithelial ovarian carcinoma are also summarized. Finally, the anticipated role of aflibercept in the treatment of epithelial ovarian carcinoma is also discussed. PMID:19519199

  5. Expression of mutant protein p53 and Hsp70 and Hsp90 chaperones in cockles Cerastoderma edule affected by neoplasia.

    PubMed

    Díaz, S; Cao, A; Villalba, A; Carballal, M J

    2010-07-01

    High prevalence of disseminated neoplasia has been found in cockles Cerastoderma edule of Galicia (NW Spain). Disseminated neoplasia has been associated with high mortalities of various bivalve species. In vertebrates, proteins such as p53 and heat shock proteins (HSPs) play important roles in carcinogenesis. The protein p53 has been detected in neoplastic cells of bivalve molluscs such as Mytilus edulis, Mytilus trossulus, Mya arenaria, Spisula solidissima, Crassostrea rhizophorae and Crassostrea gigas. In this study, western blotting analyses were used to test the expression of Hsp70, Hsp90 and mutant p53 proteins in the cells and plasma of the haemolymph of cockles showing various intensities of neoplasia. Disseminated neoplasia was previously diagnosed by examination of stained haemolymph monolayers with light microscopy. In the present study, mutant p53 was detected in haemolymph cells of cockles diagnosed as affected by moderate and heavy neoplasia intensity, whereas it was not detected in cockles with either no or light neoplasia. The higher the neoplasia intensity, the higher the levels of Hsp70 and Hsp90. These proteins were not found in plasma. The results reveal the possible association between p53 and HSPs in neoplastic cells of cockles, which could prevent p53 from carrying out its functions, as occurs in human cancers.

  6. Focal epithelial hyperplasia: Case report.

    PubMed

    Puriene, Alina; Rimkevicius, Arunas; Gaigalas, Mindaugas

    2011-01-01

    The purpose of the present article is to present a 15 year-old patient with focal epithelial hyperplasia and to review the references on the subject-related etiological, pathological, diagnostic and treatment aspects. Focal epithelial hyperplasia is a rare human papilloma virus (HPV) related to oral lesion with very low frequency within our population. Surgical treatment with a biopsy was performed, acanthosis and parakeratosis are consistent histopathological features, since the patient had no history of sexual contact and HIV infection, the virus was probably acquired from environmental sources.

  7. 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.

  8. Directional distribution of neoplasia in Barrett's esophagus is not influenced by distance from the gastroesophageal junction.

    PubMed

    Cassani, Lisa; Sumner, Eric; Slaughter, James C; Yachimski, Patrick

    2013-06-01

    Accurate endoscopic detection and staging are critical for appropriate management of Barrett's esophagus (BE)-associated neoplasia. Prior investigation has demonstrated that the distribution of endoscopically detectable early neoplasia is not uniform but instead favors specific directional distributions within a short BE segment; however, it is unknown whether the directional distribution of neoplasia differs with increasing distance from the gastroesophageal junction, including in patients with long-segment BE. To identify whether directional distribution of BE-associated neoplasia is influenced by distance from the gastroesophageal junction. Retrospective cohort study. Tertiary-care referral center. Patients with either short-segment or long-segment BE undergoing EMR. EMR. Directional distribution of BE-associated neoplasia stratified by distance from gastroesophageal junction. EMR was performed on 60 lesions meeting study criteria during the specified time period. Pathology demonstrated low-grade dysplasia in 22% (13/60), high-grade dysplasia in 38% (23/60), intramucosal (T1a) adenocarcinoma in 23% (14/60), and invasive (≥ T1b) adenocarcinoma in 17% (10/60). Directional distribution of lesions was not uniform (P < .001), with 62% of lesions (37/60) located between the 1 o'clock and 5 o'clock positions. When circular statistics methodology was used, there was no difference in the directional distribution of neoplastic lesions located within 3 cm of the gastroesophageal junction compared with ≥ 3 cm from the gastroesophageal junction. Single-center study may limit external validity. The directional distribution of neoplastic foci within a BE segment is not influenced by distance of the lesion from the gastroesophageal junction. Mucosa between the 1 o'clock and 5 o'clock locations merits careful attention and endoscopic inspection in individuals with both short-segment BE and long-segment BE. Copyright © 2013 American Society for Gastrointestinal Endoscopy

  9. Prospective evaluation of fecal calprotectin as a screening biomarker for colorectal neoplasia.

    PubMed

    Limburg, Paul J; Devens, Mary E; Harrington, Jonathan J; Diehl, Nancy N; Mahoney, Douglas W; Ahlquist, David A

    2003-10-01

    Stool testing is a well established method of screening for colorectal neoplasia. Emerging data suggest that novel biomarkers may offer performance advantages over fecal occult blood. In this large, prospective study, we assessed fecal calprotectin (a leukocyte-derived protein) as a screening biomarker for colorectal neoplasia. Fecal calprotectin was directly compared to fecal hemoglobin (Hb) and colonoscopy as the existing criterion standards for stool screening and structural evaluation, respectively. Subjects included colonoscopy patients with a personal history of colorectal neoplasia, family history of colorectal cancer, or iron deficiency anemia. Stool specimens were collected before purgation, processed appropriately, and quantitatively analyzed for calprotectin (Nycomed Pharma, Oslo, Norway) and for Hb (Mayo Medical Laboratories, Rochester, MN) by masked technicians. Colonoscopies were performed by experienced endoscopists without prior knowledge of the fecal assay results. Among 412 subjects, 97 (24%) subjects had one or more colorectal neoplasms (including three with adenocarcinomas). Fecal calprotectin levels did not differ significantly between subjects with versus subjects without colorectal neoplasms (p = 0.33). Neither tumor number (p = 0.85) nor tumor size (p = 0.86) significantly influenced the observed fecal calprotectin concentrations. Estimates of the sensitivity, specificity, and positive and negative predictive values of fecal calprotectin for any colorectal neoplasms were 37%, 63%, 23%, and 76%, respectively. Comparable performance estimates for fecal Hb were 3%, 97%, 27%, and 77%, respectively. In this cohort of colonoscopy patients at above average risk, fecal calprotectin was a poor screening biomarker for colorectal neoplasia. Further investigation of tumor-derived, rather than blood-based, biomarkers may be a more rewarding approach to stool screening for colorectal neoplasia.

  10. 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. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Can the Ni classification of vessels predict neoplasia? A systematic review and meta-analysis.

    PubMed

    Mehlum, Camilla S; Rosenberg, Tine; Dyrvig, Anne-Kirstine; Groentved, Aagot Moeller; Kjaergaard, Thomas; Godballe, Christian

    2017-06-10

    The Ni classification of vascular change from 2011 is well documented for evaluating pharyngeal and laryngeal lesions, primarily focusing on cancer. In the planning of surgery it may be more relevant to differentiate neoplasia from non-neoplasia. We aimed to evaluate the ability of the Ni classification to predict laryngeal or hypopharyngeal neoplasia and to investigate if a changed cutoff value would support the recent European Laryngological Society (ELS) proposal of perpendicular vascular changes as indicative of neoplasia. PubMed, Embase, Cochrane, and Scopus databases. A systematic review and meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement. We systematically searched for publications from 2011 until 2016. All retrieved studies were reviewed and qualitatively assessed. The pooled sensitivity and specificity of the Ni classification with two different cutoffs were calculated, and bubble and summary receiver operating characteristics plots were created. The combined sensitivity of five studies (n = 687) with Ni type IV-V defined as test-positive was 0.89 (95% confidence interval [CI]: 0.76-0.95), and specificity was 0.82 (95% CI: 0.72-0.89). The equivalent combined sensitivity of four studies (n = 624) with Ni type V defined as test-positive was 0.82 (95% CI: 0.75-0.87), and specificity was 0.93 (95% CI: 0.82-0.97). The diagnostic accuracy of the Ni classification in predicting neoplasia was high, without significant difference between the two analyzed cutoff values. Implementation of the proposed ELS classification of vascular changes seems reasonable from a clinical perspective, with comparable accuracy. Attention must be drawn to the accompanying risk of exposing patients to unnecessary surgery. Laryngoscope, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

  12. Sensitivity of immunochemical faecal occult blood testing for detecting left- vs right-sided colorectal neoplasia

    PubMed Central

    Haug, U; Kuntz, K M; Knudsen, A B; Hundt, S; Brenner, H

    2011-01-01

    Background: Faecal occult blood tests (FOBTs) are used for colorectal cancer (CRC) screening. We aimed to assess the sensitivity of an immunochemical FOBT for detecting advanced colorectal neoplasia in the left vs the right colon and to explore reasons for potential differences in site-specific test performance. Methods: We prospectively measured faecal occult blood levels by a quantitative immunochemical FOBT (RIDASCREEN) in 2310 average-risk subjects undergoing screening colonoscopy. We compared diagnostic performance for subjects with left- vs right-sided advanced neoplasia, as well as patient characteristics and adenoma characteristics that have been suggested to impact faecal haemoglobin levels. Results: Sensitivities for subjects with left- vs right-sided advanced neoplasia were 33% (95% confidence interval (CI), 26–41%) and 20% (CI, 11–31%) (P=0.04) at a specificity of 95% (overall sensitivity: 29%) and the areas under the receiver-operating characteristics curve were 0.71 (CI, 0.69–0.72) and 0.60 (CI, 0.58–0.63), respectively. Pedunculated shape was strikingly more common in participants with left- vs right-sided advanced neoplasia (47% vs 14%). In logistic regression analyses adjusted for site, pedunculated shape was statistically significantly associated with test sensitivity (P=0.04). Conclusions: The immunochemical FOBT in our study was more sensitive for detecting subjects with left- vs right-sided advanced colorectal neoplasia. Our findings may stimulate further diagnostic research in the field as well as modelling analyses to estimate the potential effect of site-specific test performance on the effectiveness of annual or biennial FOBT-based screening programmes, in particular with respect to protection from right-sided CRC. PMID:21559011

  13. Incidence and risk factors for colorectal neoplasia in patients with oral squamous cell carcinoma.

    PubMed

    Kishikawa, H; Sato, K; Yamauchi, T; Katakura, A; Shibahara, T; Takano, N; Nishida, J

    2014-11-01

    Colorectal adenoma and cancer are not regarded as being associated with primary oral cancer. The aim of this study was to determine whether screening colonoscopy should be performed for patients with oral cancer in addition to the upper gastrointestinal endoscopic screening that is now routinely performed. Between 2007 and 2013, 162 patients with oral squamous cell carcinoma were enrolled at Tokyo Dental College, Ichikawa General Hospital, and 136 individuals were assigned to colonoscopic surveillance. Advanced neoplasia was defined as an adenoma ≥ 10 mm, adenoma with villous histology or high-grade dysplasia regardless of size and invasive cancer. Associations between advanced neoplasia and clinical factors, including age, sex, body mass index, physical activity, smoking, alcohol consumption and oral cancer site and staging were determined. Advanced neoplasia, including five invasive cancers, was identified in 32 (23.5%) patients. An age- and sex-adjusted multivariate analysis revealed that smoking (Brinkmann index > 400; OR = 3.24, 95% CI = 1.28-8.18), alcohol consumption (lifetime pure ethanol consumption > 600 l; OR = 2.84, 95% CI = 1.18-6.79) and a diagnosis of cancer of the floor of the mouth (OR = 7.97, 95% CI = 2.49-25.46) were independent risk factors for advanced colorectal neoplasia. The prevalence of advanced colorectal neoplasia is unexpectedly high in patients with oral cancer. It should be recognized as a second primary tumour of oral cancer. Screening of oral cancer patients by colonoscopy should be routine practice, particularly among smokers and patients with a high intake of alcohol and cancer of the floor of the mouth. Colorectal Disease © 2014 The Association of Coloproctology of Great Britain and Ireland.

  14. Uterine artery Doppler flow velocimetry parameters for predicting gestational trophoblastic neoplasia after complete hydatidiform mole, a prospective cohort study

    PubMed Central

    Asmar, Flavia Tarabini Castellani; Braga-Neto, Antonio Rodrigues; de Rezende-Filho, Jorge; Villas-Boas, Juliana Marques Simões; Charry, Rafael Cortés; Maesta, Izildinha

    2017-01-01

    OBJECTIVES: Doppler ultrasonography can be used to assess neoangiogenesis, a characteristic feature of postmolar gestational trophoblastic neoplasia. However, there is limited information on whether uterine artery Doppler flow velocimetry parameters can predict gestational trophoblastic neoplasia following a complete hydatidiform mole. The purpose of this study was as follows: 1) to compare uterine blood flow before and after complete mole evacuation between women who developed postmolar gestational trophoblastic neoplasia and those who achieved spontaneous remission, 2) to assess the usefulness of uterine Doppler parameters as predictors of postmolar gestational trophoblastic neoplasia and to determine the best parameters and cutoff values for predicting postmolar gestational trophoblastic neoplasia. METHODS: This prospective cohort study included 246 patients with a complete mole who were treated at three different trophoblastic diseases centers between 2013 and 2014. The pulsatility index, resistivity index, and systolic/diastolic ratio were measured by Doppler flow velocimetry before and 4-6 weeks after molar evacuation. Statistical analysis was performed using Wilcoxon’s test, logistic regression, and ROC analysis. RESULTS: No differences in pre- and post-evacuation Doppler measurements were observed in patients who developed postmolar gestational trophoblastic neoplasia. In those with spontaneous remission, the pulsatility index and systolic/diastolic ratio were increased after evacuation. The pre- and post-evacuation pulsatility indices were significantly lower in patients with gestational trophoblastic neoplasia (odds ratio of 13.9-30.5). A pre-evacuation pulsatility index ≤1.38 (77% sensitivity and 82% specificity) and post-evacuation pulsatility index ≤1.77 (79% sensitivity and 86% specificity) were significantly predictive of gestational trophoblastic neoplasia. CONCLUSIONS: Uterine Doppler flow velocimetry measurements, particularly pre- and post

  15. Human papillomavirus genotype distribution in cervical intraepithelial neoplasia grade 2/3 and invasive cervical cancer in Japanese women.

    PubMed

    Azuma, Yukari; Kusumoto-Matsuo, Rika; Takeuchi, Fumihiko; Uenoyama, Asami; Kondo, Kazunari; Tsunoda, Hajime; Nagasaka, Kazunori; Kawana, Kei; Morisada, Tohru; Iwata, Takashi; Aoki, Daisuke; Kukimoto, Iwao

    2014-10-01

    Human papillomavirus vaccines are being introduced worldwide and are expected to reduce the incidence of cervical cancer. Here we report a cross-sectional study using a validated human papillomavirus genotyping method to reveal the human papillomavirus prevalence and genotype distribution in Japanese women with cervical intraepithelial neoplasia Grade 2/3 and invasive cervical cancer. Cervical exfoliated cells were collected from 647 patients with abnormal cervical histology (cervical intraepithelial neoplasia Grade 2, n = 164; cervical intraepithelial neoplasia Grade 3, n = 334; and invasive cervical cancer, n = 149), and subjected to the PGMY-PCR-based genotyping assay. The association between human papillomavirus infection and lesion severity was calculated using a prevalence ratio. Overall, the prevalence of human papillomavirus deoxyribonucleic acid was 96.3% in cervical intraepithelial neoplasia Grade 2, 98.8% in cervical intraepithelial neoplasia Grade 3 and 88.0% in invasive cervical cancer (97.8% in squamous cell carcinoma and 71.4% in adenocarcinoma). The three most prevalent types were as follows: human papillomavirus 16 (29.3%), human papillomavirus 52 (27.4%) and human papillomavirus 58 (22.0%) in cervical intraepithelial neoplasia Grade 2; human papillomavirus 16 (44.9%), human papillomavirus 52 (26.0%) and human papillomavirus 58 (17.4%) in cervical intraepithelial neoplasia Grade 3; and human papillomavirus 16 (47.7%), human papillomavirus 18 (23.5%) and human papillomavirus 52 (8.7%) in invasive cervical cancer. The prevalence ratio of human papillomavirus 16 was significantly higher in cervical intraepithelial neoplasia Grade 3 compared with cervical intraepithelial neoplasia Grade 2 (prevalence ratio, 1.62; 95% confidence interval, 1.26-2.13) and in squamous cell carcinoma compared with cervical intraepithelial neoplasia Grade 3 (prevalence ratio, 1.55; 95% confidence interval, 1.25-1.87). Multiple infections decreased from cervical

  16. The Early Detection of Pancreatic Cancer: What Will it Take to Diagnose and Treat Curable Pancreatic Neoplasia?

    PubMed Central

    Lennon, Anne Marie; Wolfgang, Christopher L.; Canto, Marcia Irene; Klein, Alison P.; Herman, Joseph M.; Goggins, Michael; Fishman, Elliot K.; Kamel, Ihab; Weiss, Matthew J.; Diaz, Luis A.; Papadopoulos, Nickolas; Kinzler, Kenneth W.; Vogelstein, Bert; Hruban, Ralph H.

    2014-01-01

    Pancreatic cancer is the deadliest of all solid malignancies. Early detection offers the best hope for a cure, but characteristics of this disease such as the lack of early clinical symptoms, make the early detection difficult. Recent genetic mapping of the molecular evolution of pancreatic cancer suggests that a large window of opportunity exists for the early detection of pancreatic neoplasia, and developments in cancer genetics offer new, potentially highly specific, approaches for screening for curable pancreatic neoplasia. We review the challenges of screening for early pancreatic neoplasia, as well as opportunities presented by incorporating molecular genetics into these efforts. PMID:24924775

  17. Screening by Total Colonoscopy Following Fecal Immunochemical Tests and Determinants of Colorectal Neoplasia in Japanese Men With Alcohol Dependence.

    PubMed

    Mizukami, Takeshi; Yokoyama, Akira; Yokoyama, Tetsuji; Onuki, Shuka; Maruyama, Katsuya

    2017-03-09

    Alcohol consumption increases the risk of colorectal adenoma and cancer. The fecal immunochemical test (FIT) is a widely used screening method for detecting colorectal neoplasia. We evaluated the results of screening and risk factors for colorectal neoplasia in individuals with alcohol dependence. Total colonoscopic screening was performed for 1006 Japanese men with alcohol dependence (462 FIT-positive and 544 FIT-negative). Advanced neoplasia was defined as neoplasia ≥10 mm, villous or tubulovillous adenoma, high-grade adenoma, or carcinoma. The detection rates for non-advanced adenoma, advanced neoplasia and intramucosal or invasive carcinoma were 38.7%, 39.4% and 9.7% for the FIT-positive group, and 33.3%, 10.8% and 2.2% for the FIT-negative group, respectively. Advanced neoplasia, especially carcinoma, was detected more frequently in the distal colon than in the proximal colon in the FIT-positive group. The respective multivariate odds ratios (ORs; 95% confidence interval) for non-advanced adenoma and advanced neoplasia were 2.83 (2.06–3.88) and 9.13 (6.19–13.5) for a positive FIT (vs. negative), 1.68 (1.39–2.02) and 1.83 (1.45–2.30) for age (per +10 years), 1.54 (1.06–2.23) and 1.88 (1.17–3.03) for current smoking (vs. non-smokers), and 1.35 (0.96–1.92) and 1.59 (1.02–2.48) for the presence of marked macrocytosis (mean corpuscular volume ≥106 fl vs. <106 fl). Genetic polymorphisms of alcohol dehydrogenase-1B and aldehyde dehydrogenase-2 did not affect the risk of colorectal neoplasia. The detection rate for advanced colorectal neoplasia was extremely high in the FIT-positive group but remained high even in the FIT-negative group. An older age, smoking and macrocytosis were predictors of advanced colorectal neoplasia. Total colonoscopic screening was performed for 1006 Japanese alcoholic men (462 fecal immunochemical test [FIT]-positive and 544 FIT-negative). The detection rate for advanced colorectal neoplasia was extremely high in the FIT

  18. Is Endoscopic Ultrasound (EUS) necessary in the pre-therapeutic assessment of Barrett’s esophagus with early neoplasia?

    PubMed Central

    Fernández-Sordo, Jacobo Ortiz; Konda, Vani J.A.; Chennat, Jennifer; Madrigal-Hoyos, Erika; Posner, Mitchell C.; Ferguson, Mark K.

    2012-01-01

    Endoscopic ultrasound (EUS) is considered the most accurate tool for the TNM staging of esophageal cancer, but its role in early Barrett’s neoplasia is still debatable. The aim was to evaluate the utility of EUS in Barrett’s patients prior to therapy. Retrospective review of 109 patients enrolled in a treatment protocol for Barrett’s neoplasia in our institution. EUS assessment was classified as suspicious for invasion in 19 patients; 84% of them had no evidence of invasion in final pathology. The assessment of depth of invasion of Barrett’s neoplasia based solely on EUS findings leads to overstaging in most patients. PMID:23205307

  19. Tuberous sclerosis complex 1: an epithelial tumor suppressor essential to prevent spontaneous prostate cancer in aged mice.

    PubMed

    Kladney, Raleigh D; Cardiff, Robert D; Kwiatkowski, David J; Chiang, Gary G; Weber, Jason D; Arbeit, Jeffrey M; Lu, Zhi Hong

    2010-11-01

    The phosphoinositide 3-kinase (PI3K) pathway regulates mammalian cell growth, survival, and motility and plays a major pathogenetic role in human prostate cancer (PCa). However, the oncogenic contributions downstream of the PI3K pathway made by mammalian target of rapamycin complex 1 (mTORC1)-mediated cell growth signal transduction in PCa have yet to be elucidated in detail. Here, we engineered constitutive mTORC1 activation in prostate epithelium by a conditional genetic deletion of tuberous sclerosis complex 1 (Tsc1), a potent negative regulator of mTORC1 signaling. Epithelial inactivation was not immediately tumorigenic, but Tsc1-deficient mice developed prostatic intraepithelial neoplasia (mPIN) in lateral and anterior prostates by 6 months of age, with increasing disease penetrance over time. Lateral prostate lesions in 16- to 22-month-old mutant mice progressed to two types of more advanced lesions, adenomatous gland forming lesion (Type 1) and atypical glands embedded in massively expanded reactive stroma (Type 2). Both Type 1 and Type 2 lesions contained multiple foci of microinvasive carcinoma. Epithelial neoplastic and atypical stromal lesions persisted despite 4 weeks of RAD001 chemotherapy. Rapalogue resistance was not due to AKT or extracellular signal-regulated kinase 1/2 activation. Expression of the homeobox gene Nkx3.1 was lost in Tsc1-deficient mPIN, and it cooperated with TSC1 loss in mPIN initiation in doubly mutant Tsc1:Nkx3.1 prostatic epithelial knockout mice. Thus, TSC1 inactivation distal to PI3K and AKT activation is sufficient to activate a molecular signaling cascade producing prostatic neoplasia and focal carcinogenesis.

  20. DHEA increases epithelial markers and decreases mesenchymal proteins in breast cancer cells and reduces xenograft growth.

    PubMed

    Colín-Val, Zaira; González-Puertos, Viridiana Yazmín; Mendoza-Milla, Criselda; Gómez, Erika Olivia; Huesca-Gómez, Claudia; López-Marure, Rebeca

    2017-10-15

    Breast cancer is one of the most common neoplasias and the leading cause of cancer death in women worldwide. Its high mortality rate is linked to a great metastatic capacity associated with the epithelial-mesenchymal transition (EMT). During this process, a decrease in epithelial proteins expression and an increase of mesenchymal proteins are observed. On the other hand, it has been shown that dehydroepiandrosterone (DHEA), the most abundant steroid in human plasma, inhibits migration of breast cancer cells; however, the underlying mechanisms have not been elucidated. In this study, the in vitro effect of DHEA on the expression pattern of some EMT-related proteins, such as E-cadherin (epithelial), N-cadherin, vimentin and Snail (mesenchymal) was measured by Western blot and immunofluorescence in MDA-MB-231 breast cancer cells with invasive, metastatic and mesenchymal phenotype. Also, the in vivo effect of DHEA on xenograft tumor growth in nude mice (nu(-)/nu(-)) and on expression of the same epithelial and mesenchymal proteins in generated tumors was evaluated. We found that DHEA increased expression of E-cadherin and decreased N-cadherin, vimentin and Snail expression both in MD-MB-231 cells and in the formed tumors, possibly by DHEA-induced reversion of mesenchymal phenotype. These results were correlated with a tumor size reduction in mouse xenografts following DHEA administration either a week earlier or concurrent with breast cancer cells inoculation. In conclusion, DHEA could be useful in the treatment of breast cancer with mesenchymal phenotype. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Computational modeling of epithelial tissues.

    PubMed

    Smallwood, Rod

    2009-01-01

    There is an extensive literature on the computational modeling of epithelial tissues at all levels from subcellular to whole tissue. This review concentrates on behavior at the individual cell to whole tissue level, and particularly on organizational aspects, and provides an indication of where information from other areas, such as the modeling of angiogenesis, is relevant. The skin, and the lining of all of the body cavities (lung, gut, cervix, bladder etc) are epithelial tissues, which in a topological sense are the boundary between inside and outside the body. They are thin sheets of cells (usually of the order of 0.5 mm thick) without extracellular matrix, have a relatively simple structure, and contain few types of cells. They have important barrier, secretory and transport functions, which are essential for the maintenance of life, so homeostasis and wound healing are important aspects of the behavior of epithelial tissues. Carcinomas originate in epithelial tissues.There are essentially two approaches to modeling tissues--to start at the level of the tissue (i.e., a length scale of the order of 1 mm) and develop generalized equations for behavior (a continuum approach); or to start at the level of the cell (i.e., a length scale of the order of 10 µm) and develop tissue behavior as an emergent property of cellular behavior (an individual-based approach). As will be seen, these are not mutually exclusive approaches, and they come in a variety of flavors.

  2. Epithelial histogenesis during tooth development.

    PubMed

    Lesot, H; Brook, A H

    2009-12-01

    This paper reviews the current understanding of the progressive changes mediating dental epithelial histogenesis as a basis for future collaborative studies. Tooth development involves morphogenesis, epithelial histogenesis and cell differentiation. The consecutive morphological stages of lamina, bud, cap and bell are also characterized by changes in epithelial histogenesis. Differential cell proliferation rates, apoptosis, and alterations in adhesion and shape lead to the positioning of groups of cells with different functions. During tooth histo-morphogenesis changes occur in basement membrane composition, expression of signalling molecules and the localization of cell surface components. Cell positional identity may be related to cell history. Another important parameter is cell plasticity. Independently of signalling molecules, which play a major role in inducing or modulating specific steps, cell-cell and cell-matrix interactions regulate the plasticity/rigidity of particular domains of the enamel organ. This involves specifying in space the differential growth and influences the progressive tooth morphogenesis by shaping the epithelial-mesenchymal junction. Deposition of a mineralized matrix determines the final shape of the crown. All data reviewed in this paper were investigated in the mouse.

  3. Prophylactic chemotherapy for hydatidiform mole to prevent gestational trophoblastic neoplasia.

    PubMed

    Wang, Qiuyi; Fu, Jing; Hu, Lina; Fang, Fang; Xie, Lingxia; Chen, Hengxi; He, Fan; Wu, Taixiang; Lawrie, Theresa A

    2017-09-11

    This is an update of the original Cochrane Review published in Cochrane Library, Issue 10, 2012.Hydatidiform mole (HM), also called a molar pregnancy, is characterised by an overgrowth of foetal chorionic tissue within the uterus. HMs may be partial (PM) or complete (CM) depending on their gross appearance, histopathology and karyotype. PMs usually have a triploid karyotype, derived from maternal and paternal origins, whereas CMs are diploid and have paternal origins only. Most women with HM can be cured by evacuation of retained products of conception (ERPC) and their fertility preserved. However, in some women the growth persists and develops into gestational trophoblastic neoplasia (GTN), a malignant form of the disease that requires treatment with chemotherapy. CMs have a higher rate of malignant transformation than PMs. It may be possible to reduce the risk of GTN in women with HM by administering prophylactic chemotherapy (P-Chem). However, P-Chem given before or after evacuation of HM to prevent malignant sequelae remains controversial, as the risks and benefits of this practice are unclear. To evaluate the effectiveness and safety of P-Chem to prevent GTN in women with a molar pregnancy. To investigate whether any subgroup of women with HM may benefit more from P-Chem than others. For the original review we performed electronic searches in the Cochrane Gynaecological Cancer Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 2, 2012), MEDLINE (1946 to February week 4, 2012) and Embase (1980 to 2012, week 9). We developed the search strategy using free text and MeSH. For this update we searched the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 5, 2017), MEDLINE (February 2012 to June week 1, 2017) and Embase (February 2012 to 2017, week 23). We also handsearched reference lists of relevant literature to identify additional studies and searched trial registries. We included randomised controlled trials

  4. Enhancement of regression of cervical intraepithelial neoplasia II (moderate dysplasia) with topically applied all-trans-retinoic acid: a randomized trial.

    PubMed

    Meyskens, F L; Surwit, E; Moon, T E; Childers, J M; Davis, J R; Dorr, R T; Johnson, C S; Alberts, D S

    1994-04-06

    Retinoids enhance differentiation of most epithelial tissues. Epidemiologic studies have shown an inverse relationship between dietary intake or serum levels of vitamin A and the development of cervical dysplasia and/or cervical cancer. Pilot and phase I investigations demonstrated the feasibility of the local delivery of all-trans-retinoic acid (RA) to the cervix using a collagen sponge insert and cervical cap. A phase II trial produced a clinical complete response rate of 50%. This randomized phase III trial was designed to determine whether topically applied RA reversed moderate cervical intraepithelial neoplasia (CIN) II or severe CIN. Analyses were based on 301 women with CIN (moderate dysplasia, 151 women; severe dysplasia, 150 women), evaluated by serial colposcopy, Papanicolaou cytology, and cervical biopsy. Cervical caps with sponges containing either 1.0 mL of 0.372% beta-trans-RA or a placebo were inserted daily for 4 days when women entered the trial, and for 2 days at months 3 and 6. Patients receiving treatment and those receiving placebo were similar with respect to age, ethnicity, birth-control methods, histologic features of the endocervical biopsy specimen and koilocytotic atypia, and percentage of involvement of the cervix at study. Treatment effects were compared using Fisher's exact test and logistic regression methods. Side effects were recorded, and differences were compared using Fisher's exact test. RA increased the complete histologic regression rate of CIN II from 27% in the placebo group to 43% in the retinoic acid treatment group (P = .041). No treatment difference between the two arms was evident in the severe dysplasia group. More vaginal and vulvar side effects were seen in the patients receiving RA, but these effects were mild and reversible. A short course of locally applied RA can reverse CIN II, but not more advanced dysplasia, with acceptable local side effects. A derivative of vitamin A can reverse or suppress an epithelial

  5. 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

  6. 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

  7. Epithelial TRPV1 Signaling Accelerates Gingival Epithelial Cell Proliferation

    PubMed Central

    Takahashi, N.; Matsuda, Y.; Yamada, H.; Tabeta, K.; Nakajima, T.; Murakami, S.; Yamazaki, K.

    2014-01-01

    Transient receptor potential cation channel subfamily V member 1 (TRPV1), a member of the calcium-permeable thermosensitive transient receptor potential superfamily, is a sensor of thermal and chemical stimuli. TRPV1 is activated by noxious heat (> 43°C), acidic conditions (pH < 6.6), capsaicin, and endovanilloids. This pain receptor was discovered on nociceptive fibers in the peripheral nervous system. TRPV1 was recently found to be expressed by non-neuronal cells, such as epithelial cells. The oral gingival epithelium is exposed to multiple noxious stimuli, including heat and acids derived from endogenous and exogenous substances; however, whether gingival epithelial cells (GECs) express TRPV1 is unknown. We show that both TRPV1 mRNA and protein are expressed by GECs. Capsaicin, a TRPV1 agonist, elevated intracellular Ca2+ levels in the gingival epithelial cell line, epi 4. Moreover, TRPV1 activation in epi 4 cells accelerated proliferation. These responses to capsaicin were inhibited by a specific TRPV1 antagonist, SB-366791. We also observed GEC proliferation in capsaicin-treated mice in vivo. No effects were observed on GEC apoptosis by epithelial TRPV1 signaling. To examine the molecular mechanisms underlying this proliferative effect, we performed complementary (c)DNA microarray analysis of capsaicin-stimulated epi 4 cells. Compared with control conditions, 227 genes were up-regulated and 232 genes were down-regulated following capsaicin stimulation. Several proliferation-related genes were validated by independent experiments. Among them, fibroblast growth factor-17 and neuregulin 2 were significantly up-regulated in capsaicin-treated epi 4 cells. Our results suggest that functional TRPV1 is expressed by GECs and contributes to the regulation of cell proliferation. PMID:25266715

  8. Multiple endocrine neoplasia syndrome type 1: institution, management, and data analysis of a nationwide multicenter patient database.

    PubMed

    Giusti, Francesca; Cianferotti, Luisella; Boaretto, Francesca; Cetani, Filomena; Cioppi, Federica; Colao, Annamaria; Davì, Maria Vittoria; Faggiano, Antongiulio; Fanciulli, Giuseppe; Ferolla, Piero; Ferone, Diego; Fossi, Caterina; Giudici, Francesco; Gronchi, Giorgio; Loli, Paola; Mantero, Franco; Marcocci, Claudio; Marini, Francesca; Masi, Laura; Opocher, Giuseppe; Beck-Peccoz, Paolo; Persani, Luca; Scillitani, Alfredo; Sciortino, Giovanna; Spada, Anna; Tomassetti, Paola; Tonelli, Francesco; Brandi, Maria Luisa

    2017-01-28

    The aim of this study was to integrate European epidemiological data on patients with multiple endocrine neoplasia type 1 by creating an Italian registry of this syndrome, including clinical and genetic characteristics and therapeutic management. Clinical, familial and genetic data of patients with multiple endocrine neoplasia type 1, diagnosed, treated, and followed-up for a mean time of 11.3 years, in 14 Italian referral endocrinological centers, were collected, over a 3-year course (2011-2013), to build a national electronic database. The Italian multiple endocrine neoplasia type 1 database includes 475 patients (271 women and 204 men), of whom 383 patients (80.6%) were classified as familial cases (from 136 different pedigrees), and 92 (19.4%) patients were sporadic cases. A MEN1 mutation was identified in 92.6% of familial cases and in 48.9% of sporadic cases. Four hundred thirty-six patients were symptomatic, presenting primary hyperparathyroidism, gastroenteropancreatic neuroendocrine tumors and pituitary tumors in 93, 53, and 41% of cases, respectively. Thirty-nine subjects, belonging to affected pedigrees positive for a MEN1 mutation, were asymptomatic at clinical and biochemical screening. Age at diagnosis of multiple endocrine neoplasia type 1 probands was similar for both familial and simplex cases (mean age 47.2 ± 15.3 years). In familial cases, diagnosis of multiple endocrine neoplasia type 1 in relatives of affected probands was made more than 10 years in advance (mean age at diagnosis 36.5 ± 17.6 years). The analysis of Italian registry of multiple endocrine neoplasia type 1 patients revealed that clinical features of Italian multiple endocrine neoplasia type 1 patients are similar to those of other western countries, and confirmed that the genetic test allowed multiple endocrine neoplasia type 1 diagnosis 10 years earlier than biochemical or clinical diagnosis.

  9. 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

  10. Medical and surgical management of reproductive neoplasia in two western lowland gorillas (Gorilla gorilla gorilla).

    PubMed

    Stringer, Elizabeth M; De Voe, Ryan S; Valea, Fidel; Toma, Sameh; Mulvaney, Gerald; Pruitt, Amy; Troan, Brigid; Loomis, Michael R

    2010-10-01

    Reports of female reproductive tract neoplasia are infrequent in great apes. Two captive-born, female western lowland gorillas (Gorilla gorilla gorilla) housed at the North Carolina Zoological Park were diagnosed with reproductive neoplasia. The first gorilla had uterine endometrial thickening and uterine fibroids diagnosed during a routine annual examination. Subsequently, the animal underwent several uterine curettage procedures in an attempt to debulk the uterine mass. Biopsy results indicated uterine adenocarcinoma. The animal was treated with an ovariohysterectomy followed by a combination of megestrol acetate and medroxyprogesterone acetate. The second gorilla was diagnosed with squamous cell carcinoma of the vagina, cervix, and uterus after presenting for intermittent vaginal bleeding of 1-month duration. This animal underwent palliative radiation therapy, receiving two rounds of radiation treatment 8 weeks apart. The following report describes the diagnosis and management of the two cases. © 2010 John Wiley & Sons A/S.

  11. Mortality rate of gestational trophoblastic neoplasia with a FIGO score of ≥13.

    PubMed

    Bolze, Pierre-Adrien; Riedl, Cécilia; Massardier, Jérôme; Lotz, Jean-Pierre; You, Benoit; Schott, Anne-Marie; Hajri, Touria; Golfier, François

    2016-03-01

    Gestational trophoblastic diseases include premalignant (partial and complete hydatidiform moles) and malignant entities referred to as gestational trophoblastic neoplasia. Use of the International Federation of Gynecology and Obstetrics prognostic score is encouraged in cases of gestational trophoblastic neoplasia to predict the potential for the development of resistance to single-agent chemotherapy. An International Federation of Gynecology and Obstetrics score of ≥7 defines a high-risk patient and requires combination chemotherapy. Appropriate and rapid diagnosis, treatment by specialized centers, and reduction of early deaths at the time of chemotherapy initiation have led to significant improvements in survival for patients with high-risk gestational trophoblastic neoplasia. There is a crucial need for the early identification of high-risk patients with gestational trophoblastic neoplasia who have an increased death risk to organize their treatment in highly specialized centers. The purpose of this study was to describe cases of gestational trophoblastic neoplasia that have resulted in death, particularly in a subgroup with an International Federation of Gynecology and Obstetrics prognostic score of ≥13, for whom low-dose etoposide and cisplatin induction chemotherapy recently was shown to reduce early death rate. We identified 974 patients from the French Center for Trophoblastic Diseases who had a diagnosis of gestational trophoblastic neoplasia from November 1999 to March 2014. Among 140 patients who were at high risk of resistance to single-agent chemotherapy (International Federation of Gynecology and Obstetrics score, ≥7), 29 patients (21%) had a score of ≥13. Mortality rate was estimated with the use of the Kaplan-Meier method. The 5-year overall mortality rate, after the exclusion of placental site trophoblastic tumors and epithelioid trophoblastic tumors, was 2% for patients with gestational trophoblastic neoplasia (95% confidence interval, 1

  12. [Topical interferon alfa-2b for primary treatment of conjunctiva-cornea intraepithelial neoplasia].

    PubMed

    Pérez de Arcelus, M; Aranguren, M; Andonegui, J

    2012-01-01

    We describe two cases of conjunctival-cornea intraepithelial neoplasia (CIN), treated with topical IFN alfa 2b. The traditional treatment for CIN is surgical excision usually with adjunctive cryotherapy. However, residual tumour may remain, which can lead to recurrence rates of more than 50%. 5-Fluorouracil, mitomicyn C and interferon α 2b are new pharmacological agents that have proved their efficacy in the treatment of CIN. As side effects are common, we present IFN α 2b as a single therapeutic agent as an effective and optimal treatment for presumed recurrent corneal and conjunctival intraepithelial neoplasia. It offers the benefits of topical therapy and avoids the risks of surgical or other interventions - specifically, ocular surface toxicity, cicatricial conjunctival changes, and limbal stem cell deficiency.

  13. 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.

  14. Frequent RET protooncogene mutations in multiple endocrine neoplasia Type 2A

    SciTech Connect

    Quadro, L.; Panariello, L.; Salvatore, D.; Carlomagno, F.; Del Prete, M.; Nunziata, V.; Colantuoni, V.; Di Giovanni, G.; Brandi, M.L.; Mannelli, M.

    1994-08-01

    The occurrence of mutations in the RET protooncogene has been investigated in 12 multiple endocrine neoplasia type 2A families and 18 cases of sporadic thyroid medullary carcinomas and pheochromocytomas. Ten of 12 families showed single base substitutions in the RET protooncogene exons 10 and 11, coding for the extracellular domain of the protein. Tumor tissues from 2 multiple endocrine neoplasia type 2A patients were analyzed at the DNA and ribonucleic acid levels and revealed the same heterozygous mutations found in the peripheral blood lymphocytes. This demonstrates that both the normal and mutant alleles are expressed. No mutations in these exons were detected in the 18 cases of sporadic tumors investigated. These data provide further evidence that the mutated RET protooncogene acts in a dominant fashion and is responsible for the pathogenesis of this syndrome. 28 refs., 2 figs., 1 tab.

  15. Cushing Disease in a patient with Multiple Endocrine Neoplasia type 2B.

    PubMed

    Kasturi, Kannan; Fernandes, Lucas; Quezado, Martha; Eid, Mary; Marcus, Leigh; Chittiboina, Prashant; Rappaport, Mark; Stratakis, Constantine A; Widemann, Brigitte; Lodish, Maya

    2017-06-01

    Multiple endocrine neoplasia type 2B (MEN2B) is a rare autosomal-dominant cancer syndrome characterized in part by metastatic medullary thyroid cancer (MTC) and pheochromocytoma. Cushing disease is a rare cause of endogenous hypercortisolism in children. We describe a 21-year-old African-American male who was diagnosed at age 10 with an ACTH-secreting pituitary microadenoma. At age 16 he developed medullary thyroid cancer and was found to have multiple endocrine neoplasia type 2B with the characteristic M918T mutation of the RET proto-oncogene. Following thyroidectomy, he was initiated on Vandetanib, a tyrosine kinase inhibitor, and has since had stable disease over the last 5 years. Our patient is the first individual with MEN2B to be described with Cushing disease. The RET oncogene may play a role in pituitary tumorigenesis; alternatively, the coexistence of these two entities may represent an extremely rare coincidence.

  16. [Association of Chlamydia trachomatis and human papilloma virus as predisposing factors in cervical intraepithelial neoplasia].

    PubMed

    González Sánchez, J L; Flores Avilés, Y; Gómez Campos, G; Montero Ramírez, A

    1995-10-01

    Human papilloma virus (HPV) has a predisposing association as cofactor in etiopathology of cervicouterine cancer; it is known also that viral infection is not enough, and there are other agents, as Chlamydia trachomatis. The objective of this study was to investigate the association of these cofactors as predisposal for intraepithelial cervical neoplasia (NIC). Prospectively, at Clinica de Colposcopia, Hospital de Ginecología y Obstetricia "Luis Castelazo Ayala", IMSS, 37 patients with cytologic, colposcopic and histological diagnosis of CIN pure or associated to HPV, underwent endocervical cytologies, and by immunofluorescence method, using monoclonal antibodies of conjugated fluoresceine, it was tried to demonstrate Chlamydia trachomatis, presence. From all patients, 12(32,4) were positive for Chlamydia trachomatis, significant percentually, and with Xi square of 0.32, non significant for this group of population. It is concluded that there is an important association of Chlamydia trachomatis and HPV, which should be taken into consideration in diagnosis and treatment of intraepithelial cervical neoplasia.

  17. Penile intraepithelial neoplasia with pagetoid features: report of an unusual variant mimicking Paget disease.

    PubMed

    Amin, Ali; Griffith, Rogers C; Chaux, Alcides

    2014-04-01

    Precancerous lesions of the penis frequently share the morphologic features of the invasive counterpart. We have recently subclassified penile intraepithelial neoplasia into differentiated, warty, and basaloid subtypes, each one with distinctive microscopic morphology. Nevertheless, in our experience, some cases depart from this classification scheme and show unusual morphologic features, hindering the proper diagnosis on routine morphology alone. Herein we present a case of penile intraepithelial neoplasia with a pagetoid growth pattern, closely mimicking Paget disease. We describe the necessary steps to reach the final diagnose, including the use of immunohistochemistry for cytokeratin (CK) 7, CK20, CK34βE12, CAM 5.2, AE1/AE3, CEA, S100, Melan-A, and p63. We also discuss other differential diagnoses that should be considered such as malignant melanoma and urothelial carcinoma in situ with pagetoid spread and less common lesions such as pagetoid dyskeratosis, clear cell papulosis, and mucinous metaplasia.

  18. Monocyte chemoattractant protein-1 in dogs affected with neoplasia or inflammation.

    PubMed

    Ishioka, Katsumi; Suzuki, Yumi; Tajima, Kana; Ohtaki, Sumire; Miyabe, Masahiro; Takasaki, Mariko; Mori, Akihiro; Momota, Yutaka; Azakami, Daigo; Sako, Toshinori

    2013-02-01

    Monocyte chemoattractant protein-1 (MCP-1) is a member of the C-C family chemokines, which mobilizes monocytes from bone marrow to the site of inflammation. To evaluate the clinical utility of canine MCP-1 as a blood test item, we measured serum MCP-1 concentrations in normal and ill dogs. Reference interval of canine MCP-1 was established as 115.6-176.9 pg/ml. Serum MCP-1 concentrations increased in the dogs affected with neoplastic (518.0 ± 84.8 pg/ml), inflammatory (257.0 ± 42.5 pg/ml) or other diseases (360.3 ± 45.2 pg/ml). The results showed high sensitivity of MCP-1 to detect neoplasia and inflammation. Moreover, MCP-1 increased in some cases in which C-reactive protein didn't increase. MCP-1 might be helpful as a screening blood test marker for detection of neoplasia and inflammation in dogs.

  19. Biomarkers of Risk for Colorectal Neoplasia (Team Project #2) — EDRN Public Portal

    Cancer.gov

    The goal of this project is to evaluate biomarkers in normal colonic mucosa to determine their relationship to the occurrence of short- and long-term colorectal neoplasia. Candidate markers have been proposed by participating investigators based on promising preliminary data. The purpose of this team project is to evaluate these markers in a common, tissue-based reference set, under a uniform, structured protocol.

  20. Plasma matrix metalloproteinase 9 as an early surrogate biomarker of advanced colorectal neoplasia.

    PubMed

    Gimeno-García, Antonio Z; Triñanes, Javier; Quintero, Enrique; Salido, Eduardo; Nicolás-Pérez, David; Adrián-de-Ganzo, Zaida; Alarcón-Fernández, Onofre; Abrante, Beatriz; Romero, Rafael; Carrillo, Marta; Ramos, Laura; Alonso, Inmaculada; Ortega, Juan; Jiménez, Alejandro

    2016-01-01

    Matrix metalloproteinases (MMPs) are overexpressed at different stages of colorectal carcinogenesis and could serve as early surrogate biomarkers of colorectal neoplasia. To assess the utility of plasma MMP2 and MMP9 levels in the detection of advanced colorectal neoplasia and their correlation with tissue levels. We analysed blood and tissue samples from patients with non-advanced adenomas (n=25), advanced adenomas (n=25), colorectal cancer (n=25) and healthy controls (n=75). Plasma and tissue gelatinase levels were determined by Luminex XMAP technology and gelatin zymography. Receiver operating characteristic (ROC) curve analysis was used to calculate the optimum cut-off for the detection of advanced colorectal neoplasia. Plasma MMP2 levels were similar between groups whatever the type of lesion. Plasma MMP9 levels were significantly higher in patients with neoplastic lesions than in healthy controls (median 292.3ng/ml vs. 139.08ng/ml, P<0.001). MMP9 levels were also higher in colorectal cancer than in non-advanced adenomas (median 314.6ng/ml vs. 274.3ng/ml, P=0.03). There was a significant correlation between plasma and tissue levels of MMP9 (r=0.5, P<0.001). The plasma MMP9 cut-off range with the highest diagnostic accuracy was between 173ng/ml and 204ng/ml (AUC=0.80 [95% CI: 0.72-0.86], P<0.001; sensitivity, 80-86% and specificity, 57-67%). Plasma MMP9 could be a surrogate biomarker for the early detection of advanced colorectal neoplasia, although its diagnostic performance could be increased by combination with other biomarkers. Copyright © 2015 Elsevier España, S.L.U. y AEEH y AEG. All rights reserved.

  1. Disparities in the Clinical Evolution of Anal Neoplasia in an HIV-Infected Cohort.

    PubMed

    Cachay, Edward R; Agmas, Wollelaw; Christopher Mathews, Wm

    2017-03-23

    A recent meta-analysis suggested that anal intraepithelial neoplasia and invasive anal cancer are more prevalent among black men having sex with men (MSM). We conducted a retrospective cohort of HIV-infected adult patients under care between 2001 and 2012. Disparities in clinical evolution of anal intraepithelial neoplasia to high-grade squamous intraepithelial lesion (HSIL) and invasive anal cancer were evaluated in a three-state Markov model adjusted for cytology misclassification. We studied sociodemographic covariate effects for each state transition using multivariable models controlling for antiretroviral therapy and infrared coagulation treatment of HSIL. Among 2804 patients with a median age of 40 years, 78% were MSM and 38% non-white. There were no disparities in HSIL prevalence (14%) by age, sex, race, or risk group. After 4.0 years of follow-up, 23 patients developed invasive anal cancer. Females and black patients had lower transition rates from 40 had lower rates of both neoplasia nor with post-baseline progression of anal intraepithelial neoplasia.

  2. Rectal Mucosal Microvascular Blood Supply Increase Is Associated with Colonic Neoplasia

    PubMed Central

    Gomes, Andrew J.; Roy, Hemant K.; Turzhitsky, Vladimir; Kim, Young; Rogers, Jeremy D.; Ruderman, Sarah; Stoyneva, Valentina; Goldberg, Michael J.; Bianchi, Laura K.; Yen, Eugene; Kromine, Alexey; Jameel, Mohammed; Backman, Vadim

    2009-01-01

    Purpose Endoscopic examination has proven effective in both detecting and preventing colorectal cancer; however, only about a quarter of eligible patients undergo screening. Even if the compliance rate increased, limited endoscopic capacity and cost would be prohibitive. There is a need for an accurate method to target colonoscopy to those most at risk of harboring colonic neoplasia. Exploiting field carcinogenesis seems to be a promising avenue. Our group recently reported that an early increase in blood supply (EIBS) is a reliable marker of field carcinogenesis in experimental models. We now investigate whether in situ detection of EIBS in the rectum can predict neoplasia elsewhere in the colon. Experimental Design We developed a novelpolarization-gated spectroscopy fiber-optic probe that allows depth-selective interrogation of microvascular blood content. Using the probe, we examined the blood content in vivo from the rectal mucosa of 216 patients undergoing screening colonoscopy. Results Microvascular blood content was increased by ~ 50% in the endoscopically normal rectal mucosa of patients harboring advanced adenomas when compared with neoplasia-free patients irrespective of lesion location. Demographic factors and nonneoplastic lesions did not confound this observation. Logistic regression using mucosal oxyhemoglobin concentration and patient age resulted in a sensitivity of 83%, a specificity of 82%, and an area under the receiver operating characteristic curve of 0.88 for the detection of advanced adenomas. Conclusions Increased microvascular blood supply in the normal rectal mucosa is associated with the presence of clinically significant neoplasia elsewhere in the colon, supporting the development of rectal EIBS as a colon cancer risk-stratification tool. PMID:19383816

  3. 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.

  4. 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.

  5. 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.

  6. Type-specific human papillomavirus prevalence in cervical intraepithelial neoplasia and cancer in Iran.

    PubMed

    Heydari, Nasrin; Oskouee, Mahin Ahangar; Vaezi, Tayebeh; Shoja, Zabihollah; Esmaeili, Heidar Ali; Hamkar, Rasool; Shahmahmoodi, Shohreh; Jalilvand, Somayeh

    2017-08-08

    In Iran, HPV vaccination is not currently included in the national vaccination program and there are no comprehensive approaches to cervical screening program. Regional data on distribution of HPV types in women is important to predict the impact of current HPV vaccines. Although several studies on distribution of HPV types in cervical precancer and cancer have been conducted in Iran, in most of them HPV positive samples were subjected to specific-primer genotyping (mainly 16 and 18), and leaving the other HPV genotypes almost undetermined. Therefore, the present study aimed to investigate the distribution of HPV types in cervical neoplasia from West and Northwest of Iran. A total of 112 women with atypia, cervical intraepithelial neoplasia, and invasive cervical cancer were included. A PCR assay was performed in all samples to detect the presence of the HPV genome using the GP5 + /6+ L1 consensus primer set. All HPV positive samples were subjected for sequencing. In overall, HPV prevalence was 20% in atypica, 44.5% in cervical intraepithelial neoplasia I, 92.3% in cervical intraepithelial neoplasia II-III, and 98.2% in invasive cervical cancer. The most frequent HPV type was HPV 16 (79.2%), which was followed by HPV types 18, 6, and 33 at the frequencies of 6.5%, 5.1%, and 2.7%, respectively. The least HPV types were found to be 31, 45, 53, 58, and 66. In conclusion, this study shows that the current HPV vaccines could have great impact to reduce the burden of cervical cancer in Iran. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  7. Quantitative Morphology of Epithelial Folds

    PubMed Central

    Štorgel, Nick; Krajnc, Matej; Mrak, Polona; Štrus, Jasna; Ziherl, Primož

    2016-01-01

    The shape of spatially modulated epithelial morphologies such as villi and crypts is usually associated with the epithelium-stroma area mismatch leading to buckling. We propose an alternative mechanical model based on intraepithelial stresses generated by differential tensions of apical, lateral, and basal sides of cells as well as on the elasticity of the basement membrane. We use it to theoretically study longitudinal folds in simple epithelia and we identify four types of corrugated morphologies: compact, invaginated, evaginated, and wavy. The obtained tissue contours and thickness profiles are compared to epithelial folds observed in invertebrates and vertebrates, and for most samples, the agreement is within the estimated experimental error. Our model establishes the groove-crest modulation of tissue thickness as a morphometric parameter that can, together with the curvature profile, be used to estimate the relative differential apicobasal tension in the epithelium. PMID:26745429

  8. Cellular systems for epithelial invagination

    PubMed Central

    2017-01-01

    Epithelial invagination is a fundamental module of morphogenesis that iteratively occurs to generate the architecture of many parts of a developing organism. By changing the physical properties such as the shape and/or position of a population of cells, invagination drives processes ranging from reconfiguring the entire body axis during gastrulation, to forming the primordia of the eyes, ears and multiple ducts and glands, during organogenesis. The epithelial bending required for invagination is achieved through a variety of mechanisms involving systems of cells. Here we provide an overview of the different mechanisms, some of which can work in combination, and outline the circumstances in which they apply. This article is part of the themed issue ‘Systems morphodynamics: understanding the development of tissue hardware’. PMID:28348256

  9. Enhancement of Early Cervical Cancer Diagnosis with Epithelial Layer Analysis of Fluorescence Lifetime Images

    PubMed Central

    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

  10. Changes in the Luminal Environment of the Colonic Epithelial Cells and Physiopathological Consequences.

    PubMed

    Blachier, François; Beaumont, Martin; Andriamihaja, Mireille; Davila, Anne-Marie; Lan, Annaïg; Grauso, Marta; Armand, Lucie; Benamouzig, Robert; Tomé, Daniel

    2017-03-01

    Evidence, mostly from experimental models, has accumulated, indicating that modifications of bacterial metabolite concentrations in the large intestine luminal content, notably after changes in the dietary composition, may have important beneficial or deleterious consequences for the colonic epithelial cell metabolism and physiology in terms of mitochondrial energy metabolism, reactive oxygen species production, gene expression, DNA integrity, proliferation, and viability. Recent data suggest that for some bacterial metabolites, like hydrogen sulfide and butyrate, the extent of their oxidation in colonocytes affects their capacity to modulate gene expression in these cells. Modifications of the luminal bacterial metabolite concentrations may, in addition, affect the colonic pH and osmolarity, which are known to affect colonocyte biology per se. Although the colonic epithelium appears able to face, up to some extent, changes in its luminal environment, notably by developing a metabolic adaptive response, some of these modifications may likely affect the homeostatic process of colonic epithelium renewal and the epithelial barrier function. The contribution of major changes in the colonocyte luminal environment in pathological processes, like mucosal inflammation, preneoplasia, and neoplasia, although suggested by several studies, remains to be precisely evaluated, particularly in a long-term perspective.

  11. Ectopic Epithelial Deaminase in IBD

    DTIC Science & Technology

    2013-10-01

    Inflammatory bowel disease (IBD) including Crohn’s disease (CD) and ulcerative colitis (UC) is a chronic intestinal disorder that is caused by...mice (carrying non-functional AID) before and after induction of colitis by oral administration of dextran sulfate sodium (DSS). 1c will...epithelial cells in colitis (months 1-18) 2a will develop and expand the mouse colony of RAG1-deficient KI/KI mice (months 1-6). In order to test the

  12. [Usefulness of human papillomavirus testing in anal intraepithelial neoplasia screening in a risk behaviour population].

    PubMed

    Padilla-España, Laura; Repiso-Jiménez, Bosco; Fernández-Sánchez, Fernando; Frieyro-Elicegui, Marta; Fernández-Morano, Teresa; Pereda, Teresa; Rivas-Ruiz, Francisco; Redondo, Maximino; de-Troya Martín, Magdalena

    2014-11-01

    The incidence of intraepithelial anal neoplasia is increasing in certain risk behaviour groups, and human papillomavirus (HPV) infection is involved in its pathogenesis. The systematic use of anal cytology, and more recently HPV detection by hybrid capture and genotyping, have been introduced into screening programs in recent decades. A retrospective cohort study was carried out on individuals with risk behaviours of developing intraepithelial anal neoplasia and who attended Sexually Transmitted Infections clinics in the Dermatology area of the Hospital Costa del Sol from January 2010 to December 2012. The intraepithelial anal neoplasia screening was performed using anal cytology and HPV genotyping. Half (50%) of the study population were HIV positive. A high frequency of anal dysplasia and presence of HPV in cytology (82.1%) and genotype (79%) was found. A statistically significant association (P<.005) was obtained between the presence of high-risk HPV genotypes and the presence of high-grade dysplasia in the second directed cytology. HPV genotyping enabled 17 cases (22%) of severe dysplasia to be identified that were under-diagnosed in the first cytology. Cases of high-grade dysplasia can be under-diagnosed by a first anal cytology. Detection of HPV can supplement this procedure, leading to the identification of those patients most at risk of developing high-grade anal dysplasia. Copyright © 2013 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  13. 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. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  14. Neoplasia of the cervix uteri and contraception: a possible adverse effect of the pill.

    PubMed

    Vessey, M P; Lawless, M; McPherson, K; Yeates, D

    1983-10-22

    The incidence of biopsy-proven cervical neoplasia during a 10-year follow-up was determined in 6838 parous women who entered the Oxford-Family Planning Association contraceptive study while using oral contraceptives and 3154 parous women who entered the study while using an intrauterine device (IUD). Risk factors for cervical neoplasia, continuation of attendance at family planning clinics, and frequency of examination by cervical cytology were similar in the two groups. All 13 cases of invasive cancer occurred in women in the oral contraceptive group; 9 had more than 6 years' use of the pill. Both carcinoma-in-situ and dysplasia also occurred more frequently in the oral contraceptive group than in the IUD group, and when the two conditions were considered together there was a trend in incidence with duration of oral contraceptive use. The incidence for all three forms of neoplasia combined rose from 0.9 per 1000 woman-years in those with up to 2 years' pill use to 2.2 per 1000 woman-years in those with more than 8 years' pill use. Amongst IUD users, there was no such trend in incidence with duration of use: the rate fluctuated around 1.0 per 1000 woman-years. The great majority of cases of invasive cancer were detected by means of cervical smears and were treated while the disease was still curable. Long-term users of oral contraceptives should have regular cervical cytological examination.

  15. Human papillomavirus and the long-term risk of cervical neoplasia.

    PubMed

    van der Graaf, Yolanda; Molijn, Anco; Doornewaard, Heleen; Quint, Wim; van Doorn, Leen-Jan; van den Tweel, Jan

    2002-07-15

    The risk of cervical neoplasia for women with normal Papanicolaou smears was calculated for those whose smears were human papillomavirus (HPV) positive and those whose smears were HPV negative. Data on 347 cases and controls were analyzed in a population-based, nested case-control study. Cases (n = 77) were women who participated in the Utrecht screening program (1976-1984) in the Netherlands and who developed cervical intraepithelial neoplasia 3 or microinvasive or invasive squamous cervical cancer after having a negative smear (1980-1986). Controls (n = 270) were matched on age (+/-5 years) and follow-up period. DNA was isolated from the Papanicolaou smears and was tested for the presence of HPV DNA by using the ultrasensitive broad-spectrum, general short-fragment polymerase chain reaction. HPV was found in 55 (71%) of the baseline smears of the 77 cases and in 31 (11%) of those of the 270 controls. The age-adjusted odds ratios for developing cervical intraepithelial neoplasia or microinvasive or invasive cervical cancer were 19.2 (95 percent confidence interval (CI): 10.3, 35.7) for HPV positivity in general, 5.4 (95% CI: 1.5, 19.5) for infection with low-risk HPV genotypes, 24.0 (95% CI: 12.4, 46.4) for high-risk HPV genotypes, and 104.8 (95% CI: 29.5, 372.7) for HPV type 16.

  16. Forerunner genes contiguous to RB1 contribute to the development of in situ neoplasia.

    PubMed

    Lee, Sangkyou; Jeong, Joon; Majewski, Tadeusz; Scherer, Steven E; Kim, Mi-Sook; Tuziak, Tomasz; Tang, Kuang S; Baggerly, Keith; Grossman, Herbert Barton; Zhou, Jain-Hua; Shen, Lanlan; Bondaruk, Jolanta; Ahmed, Saira S; Samanta, Susmita; Spiess, Philippe; Wu, Xifeng; Filipek, Slawomir; McConkey, David; Bar-Eli, Menashe; Issa, Jean-Pierre; Benedict, William F; Czerniak, Bogdan

    2007-08-21

    We used human bladder cancer as a model system and the whole-organ histologic and genetic mapping strategy to identify clonal genetic hits associated with growth advantage, tracking the evolution of bladder cancer from intraurothelial precursor lesions. Six putative chromosomal regions critical for clonal expansion of intraurothelial neoplasia and development of bladder cancer were identified by using this approach. Focusing on one of the regions, which includes the model tumor suppressor RB1, we performed allelotyping of single-nucleotide polymorphic sites and identified a 1.34-Mb segment around RB1 characterized by a loss of polymorphism associated with the initial expansion of in situ neoplasia. This segment contains several positional candidate genes referred to by us as forerunner genes that may contribute to such expansion. We subsequently concentrated our efforts on the two neighbor genes flanking RB1, namely ITM2B and CHC1L, as well as P2RY5, which is located inside RB1. Here, we report that ITM2B and P2RY5 modulated cell survival and were silenced by methylation or point mutations, respectively, and thus by functional loss may contribute to the growth advantage of neoplasia. We also show that homozygous inactivation of P2RY5 was antecedent to the loss of RB1 during tumor development, and that nucleotide substitutions in P2RY5 represent a cancer predisposing factor.

  17. 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.

  18. Familial aggregation of diabetes and hypertension in a case-control study of colorectal neoplasia.

    PubMed

    Brauer, Paula M; McKeown-Eyssen, Gail E; Jazmaji, Vartouhi; Logan, Alexander G; Andrews, David F; Jenkins, David; Marcon, Norman; Saibil, Fred; Cohen, Lawrence; Stern, Hartley; Baron, David; Greenberg, Gordon; Diamandis, Eleftherios; Kakis, Gary; Singer, William; Steiner, George

    2002-10-15

    Familial aggregation of diseases potentially associated with metabolic syndrome (diabetes mellitus, hypertension, and cardiovascular diseases) was assessed in a colonoscopy-based case-control study of colorectal neoplasia in Toronto and Ottawa, Canada, in 1993-1996. Each familial disease was analyzed by logistic regression using generalized estimating equations. Case probands had incident adenomatous polyps (n = 172) or incident (n = 25) or prevalent (n = 132) colorectal cancer (CRC), while control probands (n = 282) had a negative colonoscopy and no history of CRC or polyps. Significant effect modification was evident in the data, with the strongest positive associations between familial diabetes and colorectal neoplasia among older probands with symptoms (parents: odds ratio (OR) = 2.4, 95% confidence interval (CI): 1.2, 4.8; siblings: OR = 5.8, 95% CI: 2.6, 13.3). Familial hypertension was also associated with colorectal neoplasia among probands with symptoms (OR = 1.7, 95% CI: 1.1, 2.6). In stratified analyses, familial diabetes, hypertension, and stroke were positively associated with adenomatous polyps in subgroups of probands who were older and/or had symptoms, while only familial diabetes was possibly associated with CRC. Associations in other proband groups may have been obscured by high cumulative incidence of parental CRC. Family studies are needed to understand the contribution of specific environmental and genetic factors in accounting for the disease aggregations.

  19. TNF-α 308 G/A polymorphism and cervical intraepithelial neoplasia.

    PubMed

    Rotar, Ioana Cristina; Muresan, Daniel; Radu, Popp; Petrisor, Felicia; Apostol, Silvana; Mariana, Tanc; Butuza, Cristina; Stamatian, Florin

    2014-01-01

    The purpose of the present study was the analysis of the relationship between tumor necrosis factor-α (TNF-α) -308 G/A and cervical intraepithelial neoplasia (CIN). A prospective case-control study was performed, enrolling 78 cases of cervical intraepithelial neoplasia and 107 controls. Every patient had a complete gynecological examination with cervical sampling and colposcopy and TNF-α 308 G/A genotyping. The homozygous AA genotype was extremely rare in the study group. The GG genotype was the one most frequently encountered in all classes of cervical intraepithelial neoplasia (CIN) and controls. No statistical differences were found in global comparison between cases and controls [odds ratio (OR)=3, p=0.09], nor between well-documented cases of more evolved high-grade squamous cervical intraepithelial lesion versus controls (OR=1.2, p=0.68). However, the results were significant for invasive carcinoma (OR=10.8261, 95% confidence interval=1.0748-109.0511, p=0.0433). The presence of an A allele at -308 TNF-α represents a risk for invasive carcinoma.

  20. 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.

  1. 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 detaile