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https://www.readbyqxmd.com/read/29341443/stachyose-improves-inflammation-through-modulating-gut-microbiota-of-high-fat-diet-streptozotocin-induced-type-2-diabetes-in-rats
#1
Guimei Liu, Jia Bei, Li Liang, Guoyong Yu, Lu Li, Quanhong Li
SCOPE: The present study was undertaken to assess the effects of stachyose (STS) on type 2 diabetes in rats, and changes in the gut microbiota compared to metformin (MET). METHODS AND RESULTS: The type 2 diabetic model was successfully established via a high-fat diet (HFD) / streptozotocin (STZ) in Wistar rats, and STS or MET was administered for 4 weeks. Blood was collected to analyze biochemical parameters, pancreas for mRNA expression of related gene and contents of colon for gut microbiota...
January 16, 2018: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/29339498/mafa-missense-mutation-causes-familial-insulinomatosis-and-diabetes-mellitus
#2
Donato Iacovazzo, Sarah E Flanagan, Emily Walker, Rosana Quezado, Fernando Antonio de Sousa Barros, Richard Caswell, Matthew B Johnson, Matthew Wakeling, Michael Brändle, Min Guo, Mary N Dang, Plamena Gabrovska, Bruno Niederle, Emanuel Christ, Stefan Jenni, Bence Sipos, Maike Nieser, Andrea Frilling, Ketan Dhatariya, Philippe Chanson, Wouter W de Herder, Björn Konukiewitz, Günter Klöppel, Roland Stein, Márta Korbonits, Sian Ellard
The β-cell-enriched MAFA transcription factor plays a central role in regulating glucose-stimulated insulin secretion while also demonstrating oncogenic transformation potential in vitro. No disease-causing MAFA variants have been previously described. We investigated a large pedigree with autosomal dominant inheritance of diabetes mellitus or insulinomatosis, an adult-onset condition of recurrent hyperinsulinemic hypoglycemia caused by multiple insulin-secreting neuroendocrine tumors of the pancreas. Using exome sequencing, we identified a missense MAFA mutation (p...
January 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29338388/novel-fusion-protein-targeting-mitochondrial-dna-improves-pancreatic-islet-functional-potency-and-islet-transplantation-outcomes
#3
Juan S Danobeitia, Peter J Chlebeck, Inna Shokolenko, Xiaobo Ma, Glenn Wilson, Luis A Fernandez
Long-term graft survival is an ongoing challenge in the field of islet transplantation. With the growing demand for transplantable organs, therapies to improve organ quality and reduce the incidence of graft dysfunction are of paramount importance. We evaluated the protective role of a recombinant DNA repair protein targeted to mitochondria (Exscien I-III), as a therapeutic agent using a rodent model of pancreatic islet transplantation. We first investigated the effect of therapy on isolated rat islets cultured with pro-inflammatory cytokines (interleukin-1 β, interferon γ, and tumor necrosis factor α) for 48 h and documented a significant reduction in apoptosis by flow cytometry, improved viability by immunofluorescence, and conserved functional potency in vitro and in vivo in Exscien I-III-treated islets...
November 2017: Cell Transplantation
https://www.readbyqxmd.com/read/29337446/-endocrinopathies-induced-by-immune-checkpoint-inhibitors
#4
Jaafar Jaafar, Maria Mavromati, Jacques Philippe
Immune checkpoint Inhibitors are new immunomodulatory treatments that have proven their anti-tumor efficacy in several advanced cancers. Nevertheless, their use has paved the way for multiple immunological adverse effects that affect many systems and organs including endocrine glands such as the pituitary, thyroid, adrenal and pancreas. Hypophysitis is the most common complication of anti-CTLA-4 monoclonal antibodies, while anti-PD-1 and anti-PD-L1 antibodies cause more thyroid complications. Adrenal insufficiency and type 1 diabetes are relatively less common...
January 10, 2018: Revue Médicale Suisse
https://www.readbyqxmd.com/read/29337182/human-pancreatic-tumor-organoids-reveal-loss-of-stem-cell-niche-factor-dependence-during-disease-progression
#5
Takashi Seino, Shintaro Kawasaki, Mariko Shimokawa, Hiroki Tamagawa, Kohta Toshimitsu, Masayuki Fujii, Yuki Ohta, Mami Matano, Kosaku Nanki, Kenta Kawasaki, Sirirat Takahashi, Shinya Sugimoto, Eisuke Iwasaki, Junichi Takagi, Takao Itoi, Minoru Kitago, Yuko Kitagawa, Takanori Kanai, Toshiro Sato
Despite recent efforts to dissect the inter-tumor heterogeneity of pancreatic ductal adenocarcinoma (PDAC) by determining prognosis-predictive gene expression signatures for specific subtypes, their functional differences remain elusive. Here, we established a pancreatic tumor organoid library encompassing 39 patient-derived PDACs and identified 3 functional subtypes based on their stem cell niche factor dependencies on Wnt and R-spondin. A Wnt-non-producing subtype required Wnt from cancer-associated fibroblasts, whereas a Wnt-producing subtype autonomously secreted Wnt ligands and an R-spondin-independent subtype grew in the absence of Wnt and R-spondin...
January 10, 2018: Cell Stem Cell
https://www.readbyqxmd.com/read/29335487/increased-expression-of-glp-1r-in-proliferating-islets-of-men1-mice-is-detectable-by-68ga-ga-do3a-vs-cys40-exendin-4-pet
#6
Azita Monazzam, Joey Lau, Irina Velikyan, Su-Chen Li, Masoud Razmara, Ulrika Rosenström, Olof Eriksson, Britt Skogseid
Multiple endocrine neoplasia type 1 (MEN1) is an endocrine tumor syndrome caused by heterozygous mutations in the MEN1 tumor suppressor gene. The MEN1 pancreas of the adolescent gene carrier frequently contain diffusely spread pre-neoplasias and microadenomas, progressing to macroscopic and potentially malignant pancreatic neuroendocrine tumors (P-NET), which represents the major death cause in MEN1. The unveiling of the molecular mechanism of P-NET which is not currently understood fully to allow the optimization of diagnostics and treatment...
January 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29334562/is-a-pathological-complete-response-following-neoadjuvant-chemoradiation-associated-with-prolonged-survival-in-patients-with-pancreatic-cancer
#7
Jin He, Alex B Blair, Vincent P Groot, Ammar A Javed, Richard A Burkhart, Georgios Gemenetzis, Ralph H Hruban, Kevin M Waters, Justin Poling, Lei Zheng, Daniel Laheru, Joseph M Herman, Martin A Makary, Matthew J Weiss, John L Cameron, Christopher L Wolfgang
OBJECTIVES: To describe the survival outcome of patients with borderline resectable or locally advanced pancreatic ductal adenocarcinoma (BR/LA-PDAC) who have a pathologic complete response (pCR) following neoadjuvant chemoradiation. BACKGROUND: Patients with BR/LA-PDAC are often treated with neoadjuvant chemoradiation in an attempt to downstage the tumor. Uncommonly, a pCR may result. METHODS: A retrospective review of a prospectively maintained database was performed at a single institution...
January 12, 2018: Annals of Surgery
https://www.readbyqxmd.com/read/29334371/cooperative-targeting-of-melanoma-heterogeneity-with-an-axl-antibody-drug-conjugate-and-braf-mek-inhibitors
#8
Julia Boshuizen, Louise A Koopman, Oscar Krijgsman, Aida Shahrabi, Elke Gresnigt- van den Heuvel, Maarten A Ligtenberg, David W Vredevoogd, Kristel Kemper, Thomas Kuilman, Ji-Ying Song, Nora Pencheva, Jens Thing Mortensen, Marnix Geukes Foppen, Elisa A Rozeman, Christian U Blank, Maarten L Janmaat, David Satijn, Esther C W Breij, Daniel S Peeper, Paul W H I Parren
Intratumor heterogeneity is a key factor contributing to therapeutic failure and, hence, cancer lethality. Heterogeneous tumors show partial therapy responses, allowing for the emergence of drug-resistant clones that often express high levels of the receptor tyrosine kinase AXL. In melanoma, AXL-high cells are resistant to MAPK pathway inhibitors, whereas AXL-low cells are sensitive to these inhibitors, rationalizing a differential therapeutic approach. We developed an antibody-drug conjugate, AXL-107-MMAE, comprising a human AXL antibody linked to the microtubule-disrupting agent monomethyl auristatin E...
January 15, 2018: Nature Medicine
https://www.readbyqxmd.com/read/29332158/combined-sublethal-irradiation-and-agonist-anti-cd40-enhance-donor-t-cell-accumulation-and-control-of-autochthonous-murine-pancreatic-tumors
#9
Lindsay K Ward-Kavanagh, Kathleen M Kokolus, Timothy K Cooper, Aron E Lukacher, Todd D Schell
Tumor-reactive T lymphocytes can promote the regression of established tumors. However, their efficacy is often limited by immunosuppressive mechanisms that block T cell accumulation or function. ACT provides the opportunity to ameliorate immune suppression prior to transfer of tumor-reactive T cells to improve the therapeutic benefit. We evaluated the combination of lymphodepleting whole body irradiation (WBI) and agonist anti-CD40 (αCD40) antibody on control of established autochthonous murine neuroendocrine pancreatic tumors following the transfer of naïve tumor-specific CD8 T cells...
January 13, 2018: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29331883/curative-distal-pancreatectomy-in-patients-with-acinar-cell-carcinoma-of-pancreas-diagnosed-by-endoscopic-aspiration-via-esophago-jejunostomy-a-successful-case-report
#10
Takeomi Hamada, Atsushi Nanashima, Masahide Hiyoshi, Makoto Ikenoue, Naoya Imamura, Koichi Yano, Yoshiro Fujii, Yoshimasa Kubota, Tesshin Ban, Hiroshi Kawakami, Yuichiro Sato
INTRODUCTION: This is a case report on the advances in preoperative endoscopic-guided fine-needle-aspiration (FNA) diagnosis for pancreatic carcinoma to achieve a curative operation even in patients who have a history of total gastrectomy. CASE PRESENTATION: A 65-year-old man, who underwent total gastrectomy for gastric cancer 13 years ago, had discomfort in the left lateral abdomen. A 3-cm hypovascular mass accompanying a large distal pseudocyst in the pancreatic tail was observed on computed tomography...
January 8, 2018: International Journal of Surgery Case Reports
https://www.readbyqxmd.com/read/29331760/inotodiol-suppresses-proliferation-of-breast-cancer-in-rat-model-of-type-2-diabetes-mellitus-via-downregulation-of-%C3%AE-catenin-signaling
#11
Xia Zhang, Cuiyu Bao, Jingping Zhang
Breast cancer is amongst the most common cancers causing death of women worldwide. Breast cancer occurrence is more prominent in people with diabetes. A recent trend is management of diabetes and cancer has evolved to be natural remedy including single molecule therapy or combination. In this study, we investigated the effect of inotodiol on breast cancer growth in diabetic conditions. Inotodiol is a lanostane triterpenoid found in natural resources like edible mushroom Inonotus obliquus. We established a rat model of diabetic-breast cancer by treating female Sprague-Dawley rats with streptazotocin (STZ) at 35 mg/kg followed by induction of breast cancer by administration of 7,12-dimethylbenz(a)anthracene (DMBA) at 10 mg/kg...
January 10, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29330195/dicer1-gene-mutations-in-endocrine-tumors
#12
Michael Solarski, Fabio Rotondo, William Foulkes, John R Priest, Luis V Syro, Henriett Butz, Michael Cusimano, Kalman Kovacs
In this review, the importance of the DICER1 gene in the function of endocrine cells is discussed. There is conclusive evidence that DICER1 mutations play a crucial role in the development, progression, cell proliferation, therapeutic responsiveness and behavior of several endocrine tumors. We review the literature of DICER1 gene mutations in thyroid, parathyroid, pituitary, pineal gland, endocrine pancreas, paragangliomas, medullary, adrenocortical, ovarian, and testicular tumors. Although significant progress has been made during the last few years, much more work is needed to fully understand the significance of DICER1 mutations...
January 12, 2018: Endocrine-related Cancer
https://www.readbyqxmd.com/read/29325740/indocyanine-green-loaded-hyaluronan-derived-nanoparticles-for-fluorescence-enhanced-surgical-imaging-of-pancreatic-cancer
#13
Bowen Qi, Ayrianne J Crawford, Nicholas E Wojtynek, Megan B Holmes, Joshua J Souchek, Graca Almeida-Porada, Quan P Ly, Samuel M Cohen, Michael A Hollingsworth, Aaron M Mohs
Pancreatic ductal adenocarcinoma is highly lethal and surgical resection is the only potential curative treatment for the disease. In this study, hyaluronic acid derived nanoparticles with physico-chemically entrapped indocyanine green, termed NanoICG, were utilized for intraoperative near infrared fluorescence detection of pancreatic cancer. NanoICG was not cytotoxic to healthy pancreatic epithelial cells and did not induce chemotaxis or phagocytosis, it accumulated significantly within the pancreas in an orthotopic pancreatic ductal adenocarcinoma model, and demonstrated contrast-enhancement for pancreatic lesions relative to non-diseased portions of the pancreas...
January 8, 2018: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/29325350/-the-current-status-of-diagnosis-and-treatment-of-pancreatic-cystic-neoplasm-in-china-a-report-of-2-251-cases
#14
(no author information available yet)
Objective: To analyze the current status of diagnosis and treatment of pancreatic cystic neoplasm(PCN)in China. Methods: Clinical data of 2 251 PCN patients who underwent surgical resection from January 2006 to December 2016 in 16 institutions was retrospectively analyzed.Excel database was created which covered 132 fields of 7 fields: general information of patients, imaging findings, preoperative blood biochemical indexes, tumor markers, surgical related data, postoperative complications and pathology. Results: Of the 2 251 patients, the male to female ratio was 1...
January 1, 2018: Zhonghua Wai Ke za Zhi [Chinese Journal of Surgery]
https://www.readbyqxmd.com/read/29324681/ppoma-review-epidemiology-aetiopathogenesis-prognosis-and-treatment
#15
REVIEW
Thais Ligiero Braga, Ralph Santos-Oliveira
Generally, pancreatic polypeptide-secreting tumor of the distal pancreas (PPoma) is classified as a rare tumor, and may occur sporadically or be associated in families or with multiple endocrine neoplasia type 1 (NEM 1). It grows slowly, reaching large dimensions at the time of diagnosis and the symptomatology is fundamentally due to the mass effect, causing either non-specific abdominal pain or symptoms suggestive of obstruction of the pancreatic or biliary duct. Therefore, when detected, they are usually malignant, with metastases mainly in the liver...
January 11, 2018: Diseases (Basel)
https://www.readbyqxmd.com/read/29318362/an-immunocapture-lc-ms-based-assay-for-serum-spink1-allows-simultaneous-quantification-and-detection-of-spink1-variants
#16
Suvi Ravela, Leena Valmu, Mykola Domanskyy, Hannu Koistinen, Leena Kylänpää, Outi Lindström, Jakob Stenman, Esa Hämäläinen, Ulf-Håkan Stenman, Outi Itkonen
Pancreatic secretory trypsin inhibitor Kazal type 1 (SPINK1) is a 6420 Da peptide produced by the pancreas, but also by several other tissues and many tumors. Some mutations of the SPINK1 gene, like the one causing amino acid change N34S, have been shown to confer susceptibility to recurrent or chronic pancreatitis. Detection of such variants are therefore of clinical utility. So far SPINK1 variants have been determined by DNA techniques. We have developed and validated an immunocapture-liquid chromatography-mass spectrometric (IC-LC-MS) assay for the detection and quantification of serum SPINK1, N34S-SPINK1, and P55S-SPINK1...
January 9, 2018: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/29317372/pancreas-ductal-adenocarcinoma-with-cystic-features-on-cross-sectional-imaging-radiologic-pathologic-correlation
#17
Seo Yeon Youn, Sung Eun Rha, Eun Sun Jung, In Seok Lee
Most pancreatic ductal adenocarcinomas (PDAs) show solid growth pattern, but ductal adenocarcinomas may demonstrate intratumoral cystic appearance or accompany peritumoral non-neoplastic cystic lesions, thus mimicking cystic pancreatic tumors on imaging studies. The histopathologic findings for PDA with cystic feature are divided into neoplastic and non-neoplastic cysts. Neoplastic cystic changes include large-duct type cysts (microcystic appearance), neoplastic mucin cysts (macrocystic appearance), colloid carcinomas (mucinous noncystic adenocarcinomas), and degenerative cystic change usually caused by hemorrhagic necrosis of tumor...
January 2018: Diagnostic and Interventional Radiology: Official Journal of the Turkish Society of Radiology
https://www.readbyqxmd.com/read/29303908/progression-of-chronic-pancreatitis-to-pancreatic-cancer-is-there-a-role-of-gene-mutations-as-a-screening-tool
#18
Sumaira Rashid, Nidhi Singh, Surabhi Gupta, Safoora Rashid, Nandini Nalika, Vikas Sachdev, Chandra Sekhar Bal, Siddhartha Datta Gupta, Shyam S Chauhan, Anoop Saraya
OBJECTIVES: Early detection of pancreatic ductal adenocarcinoma still remains a challenge. Patients with chronic pancreatitis (CP) have a markedly increased risk of pancreatic cancer. Mutations in oncogenes and/or tumor suppressor genes play a role in development of pancreatic ductal adenocarcinoma. This study assessed mutations in KRAS and p53 gene in blood as a screening tool for malignant transformation in CP patients. METHODS: This was a cohort, single-center study including 294 CP patients...
January 5, 2018: Pancreas
https://www.readbyqxmd.com/read/29302820/microscopic-venous-invasion-in-pancreatic-cancer
#19
Mihoko Yamada, Teiichi Sugiura, Yukiyasu Okamura, Takaaki Ito, Yusuke Yamamoto, Ryo Ashida, Keiko Sasaki, Masato Nagino, Katsuhiko Uesaka
BACKGROUND: Microscopic venous invasion (MVI) and the subsequent peripheral blood circulation of cancer cells are considered to be the primary route for systemic dissemination of pancreatic cancer. METHODS: Patients who underwent pancreatectomy for invasive ductal carcinoma of the pancreas between January 2007 and December 2015 were retrospectively reviewed. The prognostic significance of MVI was analyzed. RESULTS: A total of 352 patients underwent pancreatectomy for invasive ductal carcinoma of the pancreas...
January 4, 2018: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/29300189/bcor-ccnb3-fusion-positive-sarcomas-a-clinicopathologic-and-molecular-analysis-of-36-cases-with-comparison-to-morphologic-spectrum-and-clinical-behavior-of-other-round-cell-sarcomas
#20
Yu-Chien Kao, Adepitan A Owosho, Yun-Shao Sung, Lei Zhang, Yumi Fujisawa, Jen-Chieh Lee, Leonard Wexler, Pedram Argani, David Swanson, Brendan C Dickson, Christopher D M Fletcher, Cristina R Antonescu
BCOR-CCNB3 sarcoma (BCS) is a recently defined genetic entity among undifferentiated round cell sarcomas, which was initially classified as and treated similarly to the Ewing sarcoma (ES) family of tumors. In contrast to ES, BCS shows consistent BCOR overexpression, and preliminary evidence suggests that these tumors share morphologic features with other tumors harboring BCOR genetic alterations, including BCOR internal tandem duplication (ITD) and BCOR-MAML3. To further investigate the pathologic features, clinical behavior, and their relationship to other round cell sarcomas, we collected 36 molecularly confirmed BCSs for a detailed histologic and immunohistochemical analysis...
October 25, 2017: American Journal of Surgical Pathology
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