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https://www.readbyqxmd.com/read/28647837/targeting-metabolic-reprogramming-in-kras-driven-cancers
#1
REVIEW
Kenji Kawada, Kosuke Toda, Yoshiharu Sakai
Mutations of KRAS are found in a variety of human malignancies, including in pancreatic cancer, colorectal cancer, and non-small cell lung cancer at high frequency. To date, no effective treatments that target mutant variants of KRAS have been introduced into clinical practice. In recent years, a number of studies have shown that the oncogene KRAS plays a critical role in controlling cancer metabolism by orchestrating multiple metabolic changes. One of the metabolic hallmarks of malignant tumor cells is their dependency on aerobic glycolysis, known as the Warburg effect...
June 24, 2017: International Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28647697/analysis-of-k-ras-interactions-by-biotin-ligase-tagging
#2
Christopher Ritchie, Andrew Mack, Logan Harper, Ayna Alfadhli, Philip J S Stork, Xiaolin Nan, Eric Barklis
BACKGROUND: Mutations of the human K-Ras 4B (K-Ras) G protein are associated with a significant proportion of all human cancers. Despite this fact, a comprehensive analysis of K-Ras interactions is lacking. Our investigations focus on characterization of the K-Ras interaction network. MATERIALS AND METHODS: We employed a biotin ligase-tagging approach, in which tagged K-Ras proteins biotinylate neighbor proteins in a proximity-dependent fashion, and proteins are identified via mass spectrometry (MS) sequencing...
July 2017: Cancer Genomics & Proteomics
https://www.readbyqxmd.com/read/28647274/sonic-hedgehog-pathway-suppression-and-reactivation-accelerates-differentiation-of-rat-adipose-derived-mesenchymal-stromal-cells-toward-insulin-producing-cells
#3
Dian Dayer, Mahmoud Hashemi Tabar, Eskandar Moghimipour, Mohammad Reza Tabandeh, Ata A Ghadiri, Elham Allah Bakhshi, Mahmoud Orazizadeh, Mohammad Ali Ghafari
BACKGROUND AIMS: Sonic hedgehog (Shh) is an intercellular signaling molecule that regulates pancreas development in mammals. Manipulation of Shh signaling pathway can be used as reliable approach to improve the generation of functional insulin-producing cells (IPCs) from mesenchymal stromal cells (MSCs). METHODS: In the present study, a novel differentiation protocol was used to produce IPCs from adipose tissue-derived MSCs (ATDMSCs) based on sequential inhibition and reactivation of Shh pathway...
June 21, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28647101/the-role-of-hypertriglyceridemia-for-acute-kidney-injury-in-the-course-of-acute-pancreatitis-and-an-animal-model
#4
Congye Wu, Lei Zou, Shujing Shi, Zhihui Tong, Xiao Shen, Dongliang Yang, Lu Ke, Weiqin Li, Jieshou Li
OBJECTIVE: The aim of this study was to investigate the role of hypertriglyceridemia for acute kidney injury (AKI) in the course of acute pancreatitis. METHODS: Patients with acute pancreatitis were retrospectively divided into four groups according to admission triglyceride: normal group, mild HTG group, moderate HTG group and severe HTG group. Clinical characteristics were compared among these groups. Wild type (WT) mice and Human ApoC III transgenic (ApoCIIItg) mice were used in the next animal experiments...
June 12, 2017: Pancreatology: Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]
https://www.readbyqxmd.com/read/28646638/corrigendum-to-oncolytic-adenovirus-expressing-relaxin-ydc002-enhances-therapeutic-efficacy-of-gemcitabine-against-pancreatic-cancer-cancer-lett-396-2017-155-166
#5
Kyung Hee Jung, Il-Kyu Choi, Hee-Seung Lee, Hong Hua Yan, Mi Kwon Son, Hyo Min Ahn, JinWoo Hong, Chae-Ok Yun, Soon-Sun Hong
No abstract text is available yet for this article.
June 21, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28646417/mesenchymal-stem-cell-therapy-for-acute-and-chronic-pancreatitis
#6
REVIEW
Kazumichi Kawakubo, Shunsuke Ohnishi, Masaki Kuwatani, Naoya Sakamoto
Mesenchymal stem cells (MSCs) have attracted attention as a cell source for regenerative medicine. In particular, MSCs have an anti-inflammatory effect by secreting several kinds of bioactive molecules. MSC therapy is now being applied to various gastrointestinal diseases, such as graft-versus-host disease, inflammatory bowel disease, and liver cirrhosis. Therefore, MSC therapy has the potential to be a novel treatment for acute and chronic pancreatitis by suppressing inflammation. Several studies have investigated the effect of MSC therapy on acute and chronic pancreatitis, but the underlying mechanisms remain unknown...
June 23, 2017: Journal of Gastroenterology
https://www.readbyqxmd.com/read/28646284/chd1l-expression-increases-tumor-progression-and-acts-as-a-predictive-biomarker-for-poor-prognosis-in-pancreatic-cancer
#7
Chuan Liu, Xiaowei Fu, Zhiwei Zhong, Jing Zhang, Haiyan Mou, Qiong Wu, Tianle Sheng, Bo Huang, Yeqing Zou
BACKGROUND: The chromodomain helicase/ATPase DNA binding protein 1-like gene (CHD1L) plays a key role in controlling various cellular phenomena, including immune-mediated inflammation, transformation, apoptosis, cell cycle progression, and proliferation. METHODS: This study investigated the function and clinical significance of CHD1L protein expression in pancreatic cancer (PC). We analyzed CHD1L expression in surgical specimens from 112 PC patients. The correlation between the clinical characteristics and prognosis was also determined...
June 23, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28646282/surgery-for-pancreatic-ductal-adenocarcinoma
#8
REVIEW
R Vera, L Díez, E Martín Pérez, J C Plaza, A Sanjuanbenito, A Carrato
Surgical resection is the only potentially curative option in the treatment of pancreatic ductal adenocarcinoma. Preoperative radiological imaging allows to rule out the presence of metastases. Three resectability categories are established based on the radiological findings depending on the degree of contact between the tumor and the blood vessels. Histological confirmation of malignancy is only required in cases of borderline or non-resectable tumors, prior to neoadjuvant treatment initiation. Diagnostic laparoscopy is recommended in the presence of large tumors of the body or tail and in borderline tumors to explore the possibility of resection and to apply treatment with curative intent, as well as in those cases with high level of biomarkers to rule out peritoneal involvement...
June 23, 2017: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/28646244/increased-soluble-vcam-1-and-normal-p-selectin-in-cystic-fibrosis-a-cross-sectional-study
#9
Jan K Nowak, Irena Wojsyk-Banaszak, Edyta Mądry, Andrzej Wykrętowicz, Patrycja Krzyżanowska, Sławomira Drzymała-Czyż, Agata Nowicka, Andrzej Pogorzelski, Ewa Sapiejka, Wojciech Skorupa, Mariusz Szczepanik, Aleksandra Lisowska, Jaroslaw Walkowiak
PURPOSE: As life expectancy in cystic fibrosis (CF) increases, questions regarding its potential impact on cardiovascular health arise. Soluble vascular cell adhesion molecule 1 (sVCAM-1), P-selectin (sP-selectin) are proposed as biomarkers of cardiovascular disease. We aimed to: compare their concentrations in clinically stable CF patients and healthy subjects (HS) and verify whether they independently correlate with CF characteristics. METHODS: Serum sVCAM-1 and sP-selectin levels were measured using ELISA...
June 23, 2017: Lung
https://www.readbyqxmd.com/read/28646158/metabolic-recovery-of-lipodystrophy-liver-steatosis-and-pancreatic-%C3%AE-cell-proliferation-after-the-withdrawal-of-osi-906
#10
Kazuki Tajima, Jun Shirakawa, Yu Togashi, Shunsuke Yamazaki, Tomoko Okuyama, Mayu Kyohara, Hiromi Konishi, Yasuo Terauchi
Growth factor signaling via insulin receptor (IR) and IGF-1 receptor (IGF1R) plays several important roles in the pathogenesis of metabolic syndrome and diabetes. OSI-906 (linsitinib), an anti-tumor drug, is an orally bioavailable dual inhibitor of IR and IGF1R. To investigate the recovery from metabolic changes induced by the acute inhibition of IR and IGF1R in adult mice, mice were treated with OSI-906 or a vehicle for 7 days and the results were analyzed on the last day of injection (Day 7) or after 7 or 21 days of withdrawal (Day 14 or Day 28)...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28646042/on-the-role-il-4-il-13-heteroreceptor-plays-in-regulation-of-type-1-diabetes
#11
Tobechukwu K Ukah, Alexis N Cattin-Roy, Weirong Chen, Mindy M Miller, Subhasis Barik, Habib Zaghouani
Type 1 diabetes (T1D) manifests when the insulin-producing pancreatic β cells are destroyed as a consequence of an inflammatory process initiated by lymphocytes of the immune system. The NOD mouse develops T1D spontaneously and serves as an animal model for human T1D. The IL-4Rα/IL-13Rα1 heteroreceptor (HR) serves both IL-4 and IL-13 cytokines, which are believed to function as anti-inflammatory cytokines in T1D. However, whether the HR provides a responsive element to environmental (i.e., physiologic) IL-4/IL-13 in the regulation of peripheral tolerance and the development of T1D has yet to be defined...
June 23, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28645922/management-of-high-grade-dysplasia-of-the-cystic-duct-after-cholecystectomy
#12
Maitham A Moslim, Andrew Tang, Gareth Morris-Stiff
High-grade dysplasia (HGD) of the cystic duct margin without evidence of concurrent malignancy is a rare occurrence. We present a case of a 36-year-old woman who developed gallstone pancreatitis and subsequently underwent a laparoscopic cholecystectomy. On histopathology, she was found to have HGD at the cystic duct margin. Following evaluation, she underwent excision of the cystic duct remnant with no malignancy being present on final pathology. We present this case to discuss the management of cystic duct dysplasia in the absence of gallbladder malignancy...
June 22, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28645741/chylous-ascites-due-to-idiopathic-chronic-pancreatitis-managed-with-endoscopic-stenting
#13
Amit Kumar, Harshal S Mandavdhare, Surinder S Rana, Rajesh Gupta, Vishal Sharma
Chylous ascites is an uncommon clinical entity, which usually results from congenital or acquired abnormality in proper lymphatic flow. While the common causes are related to trauma, malignancy or tuberculosis, pancreatic disorders can occasionally result in chylous ascites. Sporadic cases of chylous ascites due to acute or chronic pancreatitis or surgery for pancreatitis have been reported. The usual management is with medium chain triglycerides (MCT), total parenteral nutrition and octreotide. We report a case of a young male with idiopathic chronic pancreatitis who presented with chylous ascites which did not respond to MCT based diet and octreotide...
June 20, 2017: Clinics and Research in Hepatology and Gastroenterology
https://www.readbyqxmd.com/read/28645526/injury-induced-gp130-cytokine-signaling-in-peripheral-ganglia-is-reduced-in-diabetes-mellitus
#14
Jon P Niemi, Angela R Filous, Alicia DeFrancesco, Jane A Lindborg, Nisha A Malhotra, Gina N Wilson, Bowen Zhou, Samuel D Crish, Richard E Zigmond
Neuropathy is a major diabetic complication. While the mechanism of this neuropathy is not well-understood, it is believed to result in part from deficient nerve regeneration. Work from our laboratory established that gp130 family of cytokines are induced in animals after axonal injury and are involved in the induction of regeneration-associated genes (RAGs) and in the conditioning lesion response. Here, we examine whether a reduction of cytokine signaling occurs in diabetes. Streptozotocin (STZ) was used to destroy pancreatic β cells, leading to chronic hyperglycemia...
June 20, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28645477/the-overexpression-of-cpr-and-p450-3a4-in-pancreatic-cancer-cells-changes-the-metabolic-profile-and-increases-the-cytotoxicity-and-pro-apoptotic-activity-of-acridine-antitumor-agent-c-1748
#15
Barbara Borowa-Mazgaj, Anna Mróz, Ewa Augustin, Ewa Paluszkiewicz, Zofia Mazerska
Drug resistance is one of the major cause of pancreatic cancer treatment failure. Thus, it is still imperative to develop new active compounds and novel approach to improve drug efficacy. Here we present 9-amino-1-nitroacridine antitumor agent, C-1748, developed in our laboratory, as a candidate for pancreatic cancer treatment. We examined (i) the cellular response of pancreatic cancer cell lines: Panc-1, MiaPaCa-2, BxPC-3 and AsPC-1, differing in expression levels of commonly mutated genes for this cancer type, to C-1748 treatment and (ii) the role of P450 3A4 isoenzyme and cytochrome P450 reductase (CPR) in the modulation of this response...
June 20, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28644861/impact-of-ki67-re-assessment-at-time-of-disease-progression-in-patients-with-pancreatic-neuroendocrine-neoplasms
#16
Francesco Panzuto, Noemi Cicchese, Stefano Partelli, Maria Rinzivillo, Gabriele Capurso, Elettra Merola, Marco Manzoni, Eugenio Pucci, Elsa Iannicelli, Emanuela Pilozzi, Michele Rossi, Claudio Doglioni, Massimo Falconi, Gianfranco Delle Fave
BACKGROUND: Although re-assessment of proliferative activity by K67 evaluation during the course of neuroendocrine neoplasms (NENs) is recommended in selected patients, its impact on patients' management is not clear due to the lack of data supporting this practice. AIM: To investigate Ki67 change at time of progressive disease (PD) in entero-pancreatic NENs (EP-NENs). PATIENTS AND METHODS: Retrospective analysis of sporadic EP-NENs which received histological re-assessment after PD once radiologically documented...
2017: PloS One
https://www.readbyqxmd.com/read/28644836/biliary-drainage-improves-the-predictive-value-of-modified-glasgow-prognostic-scores-in-inoperable-pancreatic-cancer
#17
Chikara Iino, Tadashi Shimoyama, Takasato Igarashi, Tomoyuki Aihara, Kentaro Ishii, Juichi Sakamoto, Hiroshi Tono, Shinsaku Fukuda
OBJECTIVE: To assess the influence of biliary drainage to cholangitis on modified Glasgow Prognostic Score (mGPS) in patients with pancreatic cancer. METHODS: mGPS was calculated before and after biliary drainage in 47 consecutive patients with inoperable pancreatic cancer who were receiving chemotherapy. Biliary drainage was indicated for malignant obstructive jaundice that prevented the administration of chemotherapy. To elucidate mGPS values, serum levels of CRP and albumin were measured at the time of diagnosis (before biliary drainage)...
2017: PloS One
https://www.readbyqxmd.com/read/28644709/pcos-and-diabetes-mellitus-from-insulin-resistance-to-altered-beta-pancreatic-function-a-link-in-evolution
#18
Rosita A Condorelli, Aldo E Calogero, Maurizio Di Mauro, Sandro La Vignera
No abstract text is available yet for this article.
June 23, 2017: Gynecological Endocrinology
https://www.readbyqxmd.com/read/28643979/-acute-pancreatitis-new-aspects-for-the-management
#19
Olivier Windisch, Toni Raffoul, Catrina Hansen, Jean-Louis Frossard, Philippe Morel, Léo Bühler
Acute pancreatitis is a frequent disease, with a simple course in 80 % of the cases but a high morbidity and mortality in its severe form. Biliary origin and alcohol represent 80 % of the etiologies. Except endoscopic removal of gallstone for biliary origin, treatment remains symptomatic and focuses on fluid resuscitation, effective antalgia and adapted management of nutrition. This article focuses on the novelties introduced by the revision of the Classification of Atlanta in 2012 and details current guidelines for the management of the disease...
June 14, 2017: Revue Médicale Suisse
https://www.readbyqxmd.com/read/28643938/oral-application-of-a-periodontal-pathogen-impacts-serpine1-expression-and-pancreatic-islet-architecture-in-prediabetes
#20
V Ilievski, U G Bhat, S Suleiman-Ata, B A Bauer, P T Toth, S T Olson, T G Unterman, K Watanabe
BACKGROUND AND OBJECTIVES: Epidemiological studies suggest a close association between periodontitis and prediabetes/insulin resistance (IR) but whether periodontitis causes prediabetes in humans is not known. Using various animal models, we have recently established that periodontitis can be an initiator of prediabetes, which is characterized by glucose intolerance, hyperinsulinemia and IR. In addition, our in vitro studies indicated that Porphyromonas gingivalis (Pg) induced insulin secretion in MIN6 β cells and this induction was in part SerpinE1 (plasminogen activator inhibitor 1, PAI1) dependent...
June 23, 2017: Journal of Periodontal Research
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