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https://www.readbyqxmd.com/read/29145543/association-of-ipilimumab-with-safety-and-antitumor-activity-in-women-with-metastatic-or-recurrent-human-papillomavirus-related-cervical-carcinoma
#1
Stephanie Lheureux, Marcus O Butler, Blaise Clarke, Mihaela C Cristea, Lainie P Martin, Katia Tonkin, Gini F Fleming, Anna V Tinker, Hal W Hirte, Daliah Tsoref, Helen Mackay, Neesha C Dhani, Prafull Ghatage, Johanne Weberpals, Stephen Welch, Nhu-An Pham, Vinicius Motta, Valentin Sotov, Lisa Wang, Katherine Karakasis, Smitha Udagani, Suzanne Kamel-Reid, Howard Z Streicher, Patricia Shaw, Amit M Oza
Importance: Based on evidence of human papillomavirus (HPV)-induced immune evasion, immunotherapy may be an attractive strategy in cervical cancer. Ipilimumab is a fully humanized monoclonal antibody that blocks cytotoxic T-lymphocyte antigen-4 (CTLA-4), which acts to downregulate the T-cell immune response. Objective: To assess the safety and antitumor activity of ipilimumab in recurrent cervical cancer. Design, Setting, and Participants: A multicenter trial was designed for patients with metastatic cervical cancer (squamous cell carcinoma or adenocarcinoma) with measurable disease and progression after at least 1 line of platinum chemotherapy...
November 16, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/29119003/novel-associations-of-bile-acid-diarrhoea-with-fatty-liver-disease-and-gallstones-a-cohort-retrospective-analysis
#2
Richard N Appleby, Jonathan D Nolan, Ian M Johnston, Sanjeev S Pattni, Jessica Fox, Julian Rf Walters
Background: Bile acid diarrhoea (BAD) is a common cause of chronic diarrhoea with a population prevalence of primary BAD around 1%. Previous studies have identified associations with low levels of the ileal hormone fibroblast growth factor 19 (FGF19), obesity and hypertriglyceridaemia. The aim of this study was to identify further associations of BAD. Methods: A cohort of patients with chronic diarrhoea who underwent (75)selenohomocholic acid taurate (SeHCAT) testing for BAD was further analysed retrospectively...
2017: BMJ Open Gastroenterology
https://www.readbyqxmd.com/read/29107070/inflammation-driven-colon-neoplasmatogenesis-in-upa-deficient-mice-is-associated-with-an-increased-expression-of-runx-transcriptional-regulators
#3
Hara Afaloniati, George S Karagiannis, Alexandros Hardas, Theofilos Poutahidis, Katerina Angelopoulou
Deregulation of the bone morphogenetic protein (BMP) pathway has been documented in colorectal cancer (CRC). Previously, we investigated possible associations between urokinase-type plasminogen activator (uPA) deficiency and expression of extracellular constituents of BMP signaling in a newly developed mouse model of inflammation-driven intestinal neoplasmatogenesis, in which chronic colitis and CRC are induced using dextran sodium sulfate (DSS). In this report, we explored the contribution of intracellular components of Smad-mediated BMP signal transduction using the same model...
October 26, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/29093678/immune-related-adverse-events-associated-with-anti-pd-1-pd-l1-treatment-for-malignancies-a-meta-analysis
#4
Peng-Fei Wang, Yang Chen, Si-Ying Song, Ting-Jian Wang, Wen-Jun Ji, Shou-Wei Li, Ning Liu, Chang-Xiang Yan
Background: Treatment of cancers with programmed cell death protein 1 (PD-1) pathway inhibitors can lead to immune-related adverse events (irAEs), which could be serious and even fetal. Therefore, clinicians should be aware of the characteristics of irAEs associated with the use of such drugs. Methods: The MEDLINE, EMBASE, and Cochrane databases were searched to find potential studies using the following strategies: anti-PD-1/PD-L1 treatment; irAEs; and cancer. R© package Meta was used to pool incidence. Results: Forty-six studies representing 12,808 oncologic patients treated with anti-PD-1/PD-L1 agents were included in the meta-analysis...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29070013/p53-expression-in-patients-with-ulcerative-colitis-associated-with-dysplasia-and-carcinoma-a-systematic-meta-analysis
#5
Xiaohong Lu, Yuanjie Yu, Shiyun Tan
BACKGROUND: Tumor suppressor gene p53 expression has been reported in patients with ulcerative colitis (UC). However, the correlation between p53 expression and UC remains controversial. The aim of this meta-analysis was to investigate the association between p53 expression and different pathological types of UC. METHODS: Publications were searched in the PubMed, Embase, EBSCO, Wangfang, and CNKI databases. The overall odds ratios (ORs) and their corresponding 95% confidence intervals (95% CIs) were summarized in this study...
October 25, 2017: BMC Gastroenterology
https://www.readbyqxmd.com/read/28903393/eb1-protein-alteration-characterizes-sporadic-but-not-ulcerative-colitis-associated-colorectal-cancer
#6
Timo Gemoll, Sophie L Kollbeck, Karl F Karstens, Gia G Hò, Sonja Hartwig, Sarah Strohkamp, Katharina Schillo, Christoph Thorns, Martina Oberländer, Kathrin Kalies, Stefan Lehr, Jens K Habermann
BACKGROUND: While carcinogenesis in Sporadic Colorectal Cancer (SCC) has been thoroughly studied, less is known about Ulcerative Colitis associated Colorectal Cancer (UCC). This study aimed to identify and validate differentially expressed proteins between clinical samples of SCC and UCC to elucidate new insights of UCC/SCC carcinogenesis and progression. RESULTS: Multiplex-fluorescence two-dimensional gel electrophoresis (2-D DIGE) and mass spectrometry identified 67 proteoforms representing 43 distinct proteins...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28814670/mtg16-is-a-tumor-suppressor-in-colitis-associated-carcinoma
#7
Elizabeth M McDonough, Caitlyn W Barrett, Bobak Parang, Mukul K Mittal, J Joshua Smith, Amber M Bradley, Yash A Choksi, Lori A Coburn, Sarah P Short, Joshua J Thompson, Baolin Zhang, Shenika V Poindexter, Melissa A Fischer, Xi Chen, Jiang Li, Frank L Revetta, Rishi Naik, M Kay Washington, Michael J Rosen, Scott W Hiebert, Keith T Wilson, Christopher S Williams
MTG16 is a member of the myeloid translocation gene (MTG) family of transcriptional corepressors. While MTGs were originally identified in chromosomal translocations in acute myeloid leukemia, recent studies have uncovered a role in intestinal biology. For example, Mtg16-/- mice have increased intestinal proliferation and are more sensitive to intestinal injury in colitis models. MTG16 is also underexpressed in patients with moderate/severe ulcerative colitis. Based on these findings, we postulated that MTG16 might protect against colitis-associated carcinogenesis...
August 17, 2017: JCI Insight
https://www.readbyqxmd.com/read/28751935/chk1-promotes-dna-damage-response-bypass-following-oxidative-stress-in-a-model-of-hydrogen-peroxide-associated-ulcerative-colitis-through-jnk-inactivation-and-chromatin-binding
#8
Kathrin Reissig, Andrew Silver, Roland Hartig, Antje Schinlauer, Diana Walluscheck, Thomas Guenther, Sandra Siedentopf, Jochen Ross, Diep-Khanh Vo, Albert Roessner, Angela Poehlmann-Nitsche
Dysregulation of c-Jun N-terminal kinase (JNK) activation promoted DNA damage response bypass and tumorigenesis in our model of hydrogen peroxide-associated ulcerative colitis (UC) and in patients with quiescent UC (QUC), UC-related dysplasia, and UC-related carcinoma (UC-CRC), thereby adapting to oxidative stress. In the UC model, we have observed features of oncogenic transformation: increased proliferation, undetected DNA damage, and apoptosis resistance. Here, we show that Chk1 was downregulated but activated in the acute and quiescent chronic phases...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28751521/the-third-pathway-of-colorectal-carcinogenesis
#9
REVIEW
Carlos A Rubio, Giacomo Puppa, Giovanni de Petris, Lorand Kis, Peter T Schmidt
AIMS: The majority of the colorectal carcinomas (CRC) arise in a vast mucosal area built with columnar cells and mucus-producing goblet cells. These carcinomas evolve via the conventional (tubular/villous) adenoma-carcinoma pathway, or the serrated adenoma-carcinoma pathway. Much less frequently CRC arise in the gut-associated lymphoid tissue (GALT) mucosal domain via the third pathway of colorectal carcinogenesis. METHODS: All publications on human colorectal GALT carcinomas in the literature were reviewed...
July 27, 2017: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28699896/eb1-protein-alteration-characterizes-sporadic-but-not-ulcerative-colitis-associated-colorectal-cancer
#10
Timo Gemoll, Sophie L Kollbeck, Karl F Karstens, Gia G Hò, Sonja Hartwig, Sarah Strohkamp, Katharina Schillo, Christoph Thorns, Martina Oberländer, Kathrin Kalies, Stefan Lehr, Jens K Habermann
BACKGROUND: While carcinogenesis in Sporadic Colorectal Cancer (SCC) has been thoroughly studied, less is known about Ulcerative Colitis associated Colorectal Cancer (UCC). This study aimed to identify and validate differentially expressed proteins between clinical samples of SCC and UCC to elucidate new insights of UCC/SCC carcinogenesis and progression. RESULTS: Multiplex-fluorescence two-dimensional gel electrophoresis (2-D DIGE) and mass spectrometry identified 67 proteoforms representing 43 distinct proteins...
July 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28524162/targeted-sequencing-based-analyses-of-candidate-gene-variants-in-ulcerative-colitis-associated-colorectal-neoplasia
#11
Sanjiban Chakrabarty, Vinay Koshy Varghese, Pranoy Sahu, Pradyumna Jayaram, Bhadravathi M Shivakumar, Cannanore Ganesh Pai, Kapaettu Satyamoorthy
BACKGROUND: Long-standing ulcerative colitis (UC) leading to colorectal cancer (CRC) is one of the most serious and life-threatening consequences acknowledged globally. Ulcerative colitis-associated colorectal carcinogenesis showed distinct molecular alterations when compared with sporadic colorectal carcinoma. METHODS: Targeted sequencing of 409 genes in tissue samples of 18 long-standing UC subjects at high risk of colorectal carcinoma (UCHR) was performed to identify somatic driver mutations, which may be involved in the molecular changes during the transformation of non-dysplastic mucosa to high-grade dysplasia...
June 27, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28428105/microcarcinoid-arising-in-patients-with-long-standing-ulcerative-colitis-histological-analysis
#12
Sachie Kanada, Akira Sugita, Tetuo Mikami, Kenichi Ohashi, Hiroyuki Hayashi
Some case reports of neuroendocrine tumors and neuroendocrine carcinoma associated with ulcerative colitis (UC) have been published. Most neuroendocrine tumor cases are small lesions corresponding to microcarcinoids (MCs). However, published case reports have presented findings of MCs as single-case reports. Thus, the frequency of MCs is still unclear. In this study, we described the clinical and morphological features of 14 cases of UC-associated MCs and estimated the frequency of MCs. Consecutive patients with UC who underwent complete removal of the large intestine were assessed, and 135 patients were selected...
June 2017: Human Pathology
https://www.readbyqxmd.com/read/28383667/inactivation-of-jnk2-as-carcinogenic-factor-in-colitis-associated-and-sporadic-colorectal-carcinogenesis
#13
Wiebke Lessel, Andrew Silver, Doerthe Jechorek, Thomas Guenther, Friedrich-Wilhelm Roehl, Thomas Kalinski, Albert Roessner, Angela Poehlmann-Nitsche
We recently reported that dysregulated c-Jun N-terminal kinases (JNK) activity causes defective cell cycle checkpoint control, inducing neoplastic transformation in a cellular ulcerative colitis (UC) model. In the quiescent chronic phase of UC, p-p54 JNK was down-regulated and p-p46 JNK was up-regulated. Both were up-regulated in the acute phase. Consequently, increased p21WAF1 and γ-H2AX, two JNK-regulated proteins, induced cell cycle arrest. Their down-regulation led to checkpoint override, causing increased proliferation and undetected DNA damage in quiescent chronic phase, all characteristics of tumorigenesis...
May 1, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28350804/syndecan-1-deficiency-promotes-tumor-growth-in-a-murine-model-of-colitis-induced-colon-carcinoma
#14
Adi Binder Gallimidi, Gabriel Nussbaum, Esther Hermano, Barak Weizman, Amichay Meirovitz, Israel Vlodavsky, Martin Götte, Michael Elkin
Syndecan-1 (Sdc1) is an important member of the cell surface heparan sulfate proteoglycan family, highly expressed by epithelial cells in adult organisms. Sdc1 is involved in the regulation of cell migration, cell-cell and cell-matrix interactions, growth-factor, chemokine and integrin activity, and implicated in inflammatory responses and tumorigenesis. Gastrointestinal tract represents an important anatomic site where loss of Sdc1 expression was reported both in inflammation and malignancy. However, the biological significance of Sdc1 in chronic colitis-associated tumorigenesis has not been elucidated...
2017: PloS One
https://www.readbyqxmd.com/read/28348580/outcome-and-genetic-factors-in-igg4-associated-autoimmune-pancreatitis-and-cholangitis-a-single-center-experience
#15
Matthias Buechter, Paul Manka, Falko Markus Heinemann, Monika Lindemann, Benjamin Juntermanns, Ali Canbay, Guido Gerken, Alisan Kahraman
Introduction. Most investigations on autoimmune pancreatitis (AIP) were published on Asian cohorts while those on Caucasians are limited. However, there might be differences related to the origin. Patients and Methods. We analyzed 36 patients and compared type 1 (AIP1) with type 2 (AIP2). Results. The majority of patients suffered from AIP1 (55.6%). AIP1 patients were significantly older than AIP2 patients (54.4 versus 40.8 years). Moreover, 85.0% of AIP1 patients had concurrent autoimmune cholangitis (AIC) while 18...
2017: Gastroenterology Research and Practice
https://www.readbyqxmd.com/read/28333202/risk-of-rectal-neoplasia-after-colectomy-and-ileorectal-anastomosis-for-ulcerative-colitis
#16
Mathieu Uzzan, Julien Kirchgesner, Nadia Oubaya, Aurélien Amiot, Jean-Marc Gornet, Philippe Seksik, Stéphane Nancey, Eddy Cotte, Matthieu Allez, Gilles Boschetti, David Laharie, Nicola de Angelis, Maria Nachury, Anne-Laure Pelletier, Vered Abitbol, Mathurin Fumery, Antoine Brouquet, Anthony Buisson, Romain Altwegg, Jacques Cosnes, Yves Panis, Xavier Treton
Background and Aims: Colectomy can be required in the management of ulcerative colitis [UC]. While ileal-pouch anal anastomosis [IPAA] is the recommended reconstruction technique, ileorectal anastomosis [IRA] is still performed and might present some advantages. However, the risk of rectal neoplasia might limit its indication. The aims of our study were to determine the incidence of rectal neoplasias following IRA for UC and to identify risk factors associated with rectal carcinomas. Methods: We performed a multicenter retrospective study including patients who underwent IRA for UC from 1960 to 2014 in 13 centers...
August 1, 2017: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/28301579/a-novel-model-of-colitis-associated-cancer-in-samp1-yitfc-mice-with-crohn-s-disease-like-ileitis
#17
Paola Menghini, Luca Di Martino, Loris R Lopetuso, Daniele Corridoni, Joshua C Webster, Wei Xin, Kristen O Arseneau, Minh Lam, Theresa T Pizarro, Fabio Cominelli
Patients with inflammatory bowel disease (IBD) are at increased risk for developing colorectal cancer. Evidence suggests that colonic dysplasia and colitis-associated cancer (CAC) are often linked to repeated cycles of epithelial cell injury and repair in the context of chronic production of inflammatory cytokines. Several mouse models of CAC have been proposed, including chemical induction through exposure to dextran sulfate sodium (DSS) with the genotoxic agents azoxymethane (AOM), 1,2-dymethylhydrazine (DHM) or targeted genetic mutations...
2017: PloS One
https://www.readbyqxmd.com/read/28255443/well-differentiated-adenocarcinoma-associated-with-ulcerative-colitis
#18
Tomoko Yamamoto, Atsuko Hiroi, Hiroko Itagaki, Yoichiro Kato, Bunei Iizuka, Michio Itabashi, Noriyuki Shibata, Yoji Nagashima
OBJECTIVES: Adenocarcinoma is known to be associated with ulcerative colitis, but the diagnosis is sometimes challenging, both clinically and pathologically. METHODS AND RESULTS: We present a case of extremely well-differentiated adenocarcinoma associated with ulcerative colitis, in which preoperative diagnosis was not possible. Glands in biopsy specimens showed a serrated appearance that looked like low-grade dysplasia or regenerative mucosa. After an operation due to severe symptoms of stenosis, carcinoma was diagnosed...
2017: SAGE open medical case reports
https://www.readbyqxmd.com/read/28244237/usefulness-of-confocal-laser-endomicroscopy-to-diagnose-ulcerative-colitis-associated-neoplasia
#19
Naoki Ohmiya, Noriyuki Horiguchi, Tomomitsu Tahara, Dai Yoshida, Hyuga Yamada, Mitsuo Nagasaka, Yoshihito Nakagawa, Tomoyuki Shibata, Tetsuya Tsukamoto, Makoto Kuroda
Chromoendoscopy, narrow-band imaging (NBI), and confocal laser endomicroscopy (CLE) have been introduced in ulcerative colitis (UC)-associated neoplasia surveillance. We aimed to determine the ability of CLE to differentiate among UC-associated neoplasia (differentiated type or undifferentiated type), sporadic adenoma, and circumscribed regenerative lesions. Of 665 patients with UC, we carried out probe-based CLE (pCLE) on 12 patients with suspected UC-associated neoplasia in addition to magnifying chromoendoscopy with crystal violet and NBI...
February 28, 2017: Digestive Endoscopy: Official Journal of the Japan Gastroenterological Endoscopy Society
https://www.readbyqxmd.com/read/28225291/-a-contribution-to-the-differential-diagnostics-of-sclerosing-cholangitides
#20
Martin Blaho, Petr Dítě, Martina Bojková, Martin Rydlo, Tomáš Kupka, Pavel Svoboda, Pavel Klvaňa, Arnošt Martínek
Sclerosing cholangitides represent a group of chronic biliary obstructive diseases which include primary sclerosing cholangitis (PSC), IgG4 associated sclerosing cholangitis (IgG4-SC) and secondary sclerosing cholangitis (SSC). The manifestations of the diseases are similar, but their asymptomatic course is also frequent. IgG4-SC belongs to the group of IgG4 associated diseases and it is the most frequently related to type 1 autoimmune pancreatitis. Diagnosing of IgG4-SC is based on typical histopathological images, shape changes revealed by diagnostic imaging, serological tests, concurrent impairment of other organs and response to therapy, where IgG4-SC responds well to treatment with corticoids, whereas the only possibility for the remaining units is endoscopic intervention or liver transplantation...
December 0: Vnitr̆ní Lékar̆ství
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