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https://www.readbyqxmd.com/read/29053971/a-gut-microbial-mimic-that-hijacks-diabetogenic-autoreactivity-to-suppress-colitis
#1
Roopa Hebbandi Nanjundappa, Francesca Ronchi, Jinguo Wang, Xavier Clemente-Casares, Jun Yamanouchi, Channakeshava Sokke Umeshappa, Yang Yang, Jesús Blanco, Helena Bassolas-Molina, Azucena Salas, Hamza Khan, Robyn M Slattery, Madeleine Wyss, Catherine Mooser, Andrew J Macpherson, Laura K Sycuro, Pau Serra, Derek M McKay, Kathy D McCoy, Pere Santamaria
The gut microbiota contributes to the development of normal immunity but, when dysregulated, can promote autoimmunity through various non-antigen-specific effects on pathogenic and regulatory lymphocytes. Here, we show that an integrase expressed by several species of the gut microbial genus Bacteroides encodes a low-avidity mimotope of the pancreatic β cell autoantigen islet-specific glucose-6-phosphatase-catalytic-subunit-related protein (IGRP206-214). Studies in germ-free mice monocolonized with integrase-competent, integrase-deficient, and integrase-transgenic Bacteroides demonstrate that the microbial epitope promotes the recruitment of diabetogenic CD8+ T cells to the gut...
October 19, 2017: Cell
https://www.readbyqxmd.com/read/29053790/the-hippo-signaling-pathway-in-pancreatic-%C3%AE-cells-functions-and-regulations
#2
Amin Ardestani, Kathrin Maedler
Hippo signaling is an evolutionarily conserved pathway that critically regulates development and homeostasis of various tissues in response to a wide range of extracellular and intracellular signals. As an emerging significant player in many diseases, the Hippo pathway is also involved in the pathophysiology of diabetes on the level of the pancreatic islets. Multiple lines of evidence uncover the importance of Hippo signaling in pancreas development as well as in the regulation of β-cell survival, proliferation and regeneration...
October 18, 2017: Endocrine Reviews
https://www.readbyqxmd.com/read/29053678/assay-for-phosphorylation-and-microtubule-binding-along-with-localization-of-tau-protein-in-colorectal-cancer-cells
#3
Md Nazmul Huda, Erdenedolgor Erdene-Ochir, Cheol-Ho Pan
The microtubule-associated protein tau is a neuronal protein that localizes mostly in axons. Generally tau is essential for normal neuronal functioning because it is involved in microtubule assembly and stabilization. Besides neurons, tau is expressed in human breast, prostate, gastric, colorectal, and pancreatic cancers where it shows nearly similar structure and exerts similar functions as the neuronal tau. The amount of tau and its phosphorylation can change its function as a stabilizer of microtubules, and lead to the development of paired helical filaments in different neurodegenerative disorders, such as Alzheimer's disease...
October 10, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29053185/expression-of-the-dna-repair-gene-mlh1-correlates-with-survival-in-patients-who-have-resected-pancreatic-cancer-and-have-received-adjuvant-chemoradiation-nrg-oncology-rtog-study-9704
#4
Yaacov R Lawrence, Jennifer Moughan, Anthony M Magliocco, Alexander C Klimowicz, William F Regine, Rex B Mowat, Thomas A DiPetrillo, William Small, Jeffry P Simko, Talia Golan, Kathryn A Winter, Chandan Guha, Christopher H Crane, Adam P Dicker
BACKGROUND: The majority of patients with pancreatic cancer who undergo curative resection experience rapid disease recurrence. In previous small studies, high expression of the mismatch-repair protein mutL protein homolog 1 (MLH1) in pancreatic cancers was associated with better outcomes. The objective of this study was to validate the association between MLH1 expression and survival in patients who underwent resection of pancreatic cancer and received adjuvant chemoradiation. METHODS: Samples were obtained from the NRG Oncology Radiation Therapy Oncology Group 9704 prospective, randomized trial (clinicaltrials...
October 20, 2017: Cancer
https://www.readbyqxmd.com/read/29052825/managing-endoscopic-retrograde-cholangiopancreatography-related-complications-in-patients-referred-to-the-surgical-emergency-unit
#5
Osman Şimşek, Arife Şimşek, Sefa Ergun, Mehmet Velidedeoğlu, Kaya Sarıbeyoğlu, Salih Pekmezci
BACKGROUND: The goal of this study was to present our experience in the management of endoscopic retrograde cholangiopancreatography-related complications in patients referred to our surgical emergency unit by various endoscopy centers. METHODS: A retrospective investigation was conducted on the records of the 54 patients who were referred to our surgical emergency unit between October 2005 and January 2014 due to endoscopic retrograde cholangiopancreatography-related complications...
September 2017: Ulusal Travma Ve Acil Cerrahi Dergisi, Turkish Journal of Trauma & Emergency Surgery: TJTES
https://www.readbyqxmd.com/read/29052535/large-cell-neuroendocrine-carcinoma-of-the-kidney-with-cardiac-metastasis-a-case-report
#6
Moeka Shimbori, Kimito Osaka, Takashi Kawahara, Ryo Kasahara, Sayuki Kawabata, Kazuhide Makiyama, Keiichi Kondo, Noboru Nakaigawa, Shoji Yamanaka, Masahiro Yao
BACKGROUND: Primary large cell neuroendocrine carcinoma of the kidney is a rare and generally very aggressive disease. We present a case of a patient with primary large cell neuroendocrine carcinoma of the kidney with cardiac metastasis. CASE PRESENTATION: A 59-year-old Japanese man presented to his previous physician with hematuria. Computed tomography revealed masses in the heart and right kidney, and fluorodeoxyglucose-positron emission tomography showed abnormal uptake in the heart...
October 20, 2017: Journal of Medical Case Reports
https://www.readbyqxmd.com/read/29052441/investigational-glucagon-receptor-antagonists-in-phase-i-and-ii-clinical-trials-for-diabetes
#7
André J Scheen, Nicolas Paquot, Pierre J Lefèbvre
Despite type 2 diabetes (T2D) being recognized as a bihormonal pancreatic disease, current therapies are mainly focusing on insulin, while targeting glucagon has been long dismissed. However, glucagon receptor (GCGr) antagonists are currently investigated in clinical trials. Area covered: Following a brief description of the rationale for antagonizing GCGr in T2D, lessons from GCGr knock-out mice and pharmacological means to antagonize GCGr, a detailed description of the main results obtained with GCGr antagonists in Phase I-II clinical trials is provided...
October 20, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/29051892/autoimmune-pancreatitis-type-2-case-report
#8
Chidinma Onweni, Harika Balagoni, Jennifer M Treece, Emmanuel Addo Yobo, Archi Patel, Jennifer Phemister, Manoj Srinath, Mark F Young
A middle-aged man presents with acute pancreatitis of unknown etiology and is found to have a presentation consistent with the diagnosis of type 2 autoimmune pancreatitis (AIP). AIP is a group of rare heterogeneous diseases that are challenging to diagnose. There are 2 types of AIP. Type 1 disease is the more common worldwide than type 2 AIP. While type 1 AIP is associated with IgG4-positive antibodies, type 2 AIP is IgG4 antibody negative. Both types of AIP are responsive to corticosteroid treatment. Although type 1 AIP has more extrapancreatic manifestations and more commonly relapses, this is a case of a patient with type 2 AIP with inflammatory bowel disease and relapsing course...
October 2017: Journal of Investigative Medicine High Impact Case Reports
https://www.readbyqxmd.com/read/29051322/a-multicenter-phase-i-study-evaluating-dual-pi3k-and-braf-inhibition-with-px-866-and-vemurafenib-in-patients-with-advanced-braf-v600-mutant-solid-tumors
#9
Clinton Yam, Xiaowei Xu, Michael A Davies, Phyllis A Gimotty, Jennifer Jd Morrissette, Michael T Tetzlaff, Khalida Wani, Shujing Liu, Wanleng Deng, Meghan Buckley, Jianhua Zhao, Ravi K Amaravadi, Naomi Haas, Ragini R Kudchadkar, Anna Pavlick, Jeffrey A Sosman, Hussein Tawbi, Luke Walker, Lynn M Schuchter, Giorgos C Karakousis, Tara C Gangadhar
PURPOSE: The objectives of the study were to evaluate the safety of daily oral PX-866 in combination with twice daily vemurafenib and to identify potential predictive biomarkers for this novel combination. EXPERIMENTAL DESIGN: We conducted a phase I, open-label, dose escalation study in patients with advanced BRAF V600 mutant solid tumors. PX-866 was administered on a continuous schedule in combination with vemurafenib. Patients underwent a baseline and on-treatment biopsy after 1-week of PX-866 monotherapy for biomarker assessment...
October 19, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29051099/hyperglycemia-induced-reactive-species-trigger-structural-changes-in-human-serum-albumin-of-type-1-diabetic-subjects
#10
Zarina Arif, Km Neelofar, Mir Yasir Arfat, Asif Zaman, Akhlas Tarannum, Iffat Parveen, Shafeeque Ahmad, Md Adnan Khan, Asim Badar, Shireen Naaz Islam
Chronic oxidative stress fuels pathogenesis of a large set of diseases. Oxidative stress is the cause and consequence of numerous diseases including type 1 diabetes mellitus (T1DM), in which there is selective destruction of insulin producing pancreatic β-cells. Studies have documented that hyperglycemia produces profound stress. In vivo production of numerous reactive oxygen, nitrogen, chlorine species and lipid/sugar oxidation products are result of persistent hyperglycemia. Post-translational modifications by reactive species may create new antigenic epitopes and play a role in the development of autoimmune response...
October 16, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29050364/lncrnas-key-players-and-novel-insights-into-diabetes-mellitus
#11
REVIEW
Xiaoyun He, Chunlin Ou, Yanhua Xiao, Qing Han, Hao Li, Suxian Zhou
Long non-coding RNAs (LncRNAs) are a class of endogenous RNA molecules, which have a transcribing length of over 200 nt, lack a complete functional open reading frame (ORF), and rarely encode a functional short peptide. Recent studies have revealed that disruption of LncRNAs levels correlates with several human diseases, including diabetes mellitus (DM), a complex multifactorial metabolic disorder affecting more than 400 million people worldwide. LncRNAs are emerging as pivotal regulators in various biological processes, in the progression of DM and its associated complications, involving pancreatic β-cell disorder, insulin resistance, and epigenetic regulation, etc...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29050346/identification-of-candidate-genes-related-to-pancreatic-cancer-based-on-analysis-of-gene-co-expression-and-protein-protein-interaction-network
#12
Tiejun Zhang, Xiaojuan Wang, Zhenyu Yue
Pancreatic cancer (PC) is one of the most common causes of cancer mortality worldwide. As the genetic mechanism of this complex disease is not uncovered clearly, identification of related genes of PC is of great significance that could provide new insights into gene function as well as potential therapy targets. In this study, we performed an integrated network method to discover PC candidate genes based on known PC related genes. Utilizing the subnetwork extraction algorithm with gene co-expression profiles and protein-protein interaction data, we obtained the integrated network comprising of the known PC related genes (denoted as seed genes) and the putative genes (denoted as linker genes)...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29050119/-feasibility-of-domestic-18-f-dopa-pet-ct-scanning-in-the-differential-diagnosis-of-pancreatic-lesions-in-children-with-hyperinsulinemic-hypoglycemia
#13
M Y Zhang, J J Ge, Z Pei, K R Dong, L Chen, X Wang, Z W Zhang, X J Li, L Xi, R Q Cheng, G P Lu, Y H Guan, F H Luo
Objective: To study the feasibility of (18)F-fluoro-L-dihydroxyphenylalanine positron emission tomography/Computed tomography ((18)F-DOPA PET/CT) scanning in the localization and differential diagnosing of focal versus diffuse form of pancreas lesions in patients with hyperinsulinemic hypoglycemia (HH). Method: Twenty-four patients were diagnosed with HH between January, 2016 and February, 2017 in the Department of Pediatric Endocrinology and Inherited Metabolic Diseases, Children's Hospital of Fudan University using an integrated clinical and biochemical diagnostic protocol, domestic (18)F-DOPA PET/CT imaging technique were applied after MRI and ultrasound failed to detect pancreas lesions...
October 2, 2017: Zhonghua Er Ke za Zhi. Chinese Journal of Pediatrics
https://www.readbyqxmd.com/read/29049340/pressurized-intra-peritoneal-aerosol-chemotherapy-in-patients-suffering-from-peritoneal-carcinomatosis-of-pancreatic-adenocarcinoma
#14
Tanja Khosrawipour, Veria Khosrawipour, Urs Giger-Pabst
BACKGROUND: Patients suffering from peritoneal carcinomatosis of pancreatic adenocarcinoma were treated with Pressurized Intra Peritoneal Aerosol Chemotherapy (PIPAC), initial clinical findings are presented. METHODS: Single institution, tertiary referral center certified for therapy of peritoneal disease. Prospective data collection of PIPAC therapy with doxorubicin 1.5 mg/m2 and cisplatin 7.5 mg/m2 of body surface delivered at intervals of six weeks. The outcome criteria were microscopic pathological response, survival and adverse events (v4...
2017: PloS One
https://www.readbyqxmd.com/read/29048560/targeting-the-mesenchymal-subtype-in-glioblastoma-and-other-cancers-via-inhibition-of-diacylglycerol-kinase-alpha
#15
Inan Olmez, Shawn Love, Aizhen Xiao, Laryssa Manigat, Peyton Randolph, Brian D McKenna, Brian P Neal, Salome Boroda, Ming Li, Breanna Brenneman, Roger Abounader, Desiree Floyd, Jeongwu Lee, Ichiro Nakano, Jakub Godlewski, Agnieszka Bronisz, Erik P Sulman, Marty Mayo, Daniel Gioeli, Michael Weber, Thurl E Harris, Benjamin Purow
Background: The mesenchymal phenotype in glioblastoma (GBM) and other cancers drives aggressiveness and treatment resistance, leading to therapeutic failure and recurrence of disease. Currently, there is no successful treatment option available against the mesenchymal phenotype. Methods: We classified patient-derived GBM stem cell lines into 3 subtypes: proneural, mesenchymal, and other/classical. Each subtype's response to the inhibition of diacylglycerol kinase alpha (DGKα) was compared both in vitro and in vivo...
June 29, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/29048402/mir-3656-expression-enhances-the-chemosensitivity-of-pancreatic-cancer-to-gemcitabine-through-modulation-of-the-rhof-emt-axis
#16
Rui-Meng Yang, Ming Zhan, Sun-Wang Xu, Man-Mei Long, Lin-Hua Yang, Wei Chen, Shuai Huang, Qiang Liu, Jun Zhou, Jun Zhu, Jian Wang
The highly refractory nature of pancreatic cancer (PC) to chemotherapeutic drugs is one of the key reasons contributing to the poor prognosis of this disease. MicroRNAs (miRNAs) are key regulators of gene expression and have been implicated in a variety of processes from cancer development through to drug resistance. Herein, through miRNA profiling of gemcitabine-resistant (GR) and parental PANC-1 cell lines, we found a consistent reduction of miR-3656 in GR PANC-1 cells. miR-3656 overexpression enhanced the antitumor effect of gemcitabine, whereas silencing of miR-3656 resulted in the opposite effect...
October 19, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29047015/quality-of-online-resources-for-pancreatic-cancer-patients
#17
Lauren De Groot, Ilene Harris, Glenn Regehr, Ara Tekian, Paris-Ann Ingledew
The Internet is increasingly a source of information for pancreatic cancer patients. This disease is usually diagnosed at an advanced stage; therefore, timely access to high-quality information is critical. Our purpose is to systematically evaluate the information available to pancreatic cancer patients on the internet. An internet search using the term "pancreatic cancer" was performed, with the meta-search engines "Dogpile", "Yippy" and "Google". The top 100 websites returned by the search engines were evaluated using a validated structured rating tool...
October 18, 2017: Journal of Cancer Education: the Official Journal of the American Association for Cancer Education
https://www.readbyqxmd.com/read/29046745/the-bedside-index-for-severity-in-acute-pancreatitis-a-systematic-review-of-prospective-studies-to-determine-predictive-performance
#18
Subhash Chandra, Arvind Murali, Reena Bansal, Dipti Agarwal, Adrian Holm
Background: predicting the development of severe disease has remained a major challenge in management of acute pancreatitis. The Bedside Index for Severity in Acute Pancreatitis (BISAP) is easy to calculate from the data available in the first 24 hours. Here, we performed a systematic review to determine the prognostic accuracy of the BISAP for severe acute pancreatitis (SAP). Methods: major databases of biomedical publications were searched during the first week of October 2015. Two independent reviewers searched records in two phases...
October 2017: Journal of Community Hospital Internal Medicine Perspectives
https://www.readbyqxmd.com/read/29046394/recombinant-human-islet-amyloid-polypeptide-forms-shorter-fibrils-and-mediates-%C3%AE-cell-apoptosis-via-generation-of-oxidative-stress
#19
Richa Dubey, Pooja Minj, Nikita Malik, Devika M Sardesai, Shruti H Kulkarni, Jhankar D Acharya, Neel S Bhavesh, Shilpy Sharma, Ashutosh Kumar
Protein aggregation play an important role in many human diseases including Alzheimer's, Parkinson's and Type 2 diabetes mellitus (T2DM). Human islet amyloid polypeptide (hIAPP) forms amyloid plaques in pancreas of T2DM subjects that are involved in deteriorating islet function and in mediating β- cell apoptosis. However, the detailed mechanism of action, structure and nature of toxic hIAPP species responsible for this effect remains elusive till date mainly due to the high cost associated with the chemical synthesis of pure peptide required for these studies...
October 18, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/29045525/clinical-benefit-of-systemic-treatment-in-patients-with-advanced-pancreatic-and-gastro-intestinal-neuroendocrine-tumours-according-to-esmo-mcbs-and-asco-framework
#20
L D de Hosson, L M van Veenendaal, Y Schuller, W T Zandee, W W de Herder, M E T Tesselaar, H J Klümpen, A M E Walenkamp
BackgroundAssessment of clinical benefit of systemic treatments of rare diseases including gastroenteropancreatic neuroendocrine tumors (GEP-NET) is challenging. Recently several tools have been developed to grade clinical benefit of cancer drugs. European Society for Medical Oncology (ESMO) has developed the ESMO Magnitude of Clinical Benefit Scale (ESMO-MCBS). The American Society of Clinical Oncology (ASCO) developed and revised the ASCO framework consisting of the Net Health Benefit (NHB) score juxtaposed against the costs of the treatment...
September 26, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
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