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Laurits J Holm, Martin Haupt-Jorgensen, Jesper Larsen, Jano D Giacobini, Mesut Bilgin, Karsten Buschard
Sphingolipids are a diverse group of lipids with important roles in beta-cell biology regulating insulin folding and controlling apoptosis. Sphingolipid biosynthesis begins with the condensation of L-serine and palmitoyl-CoA. Here we tested the effect of L-serine supplementation on autoimmune diabetes development and blood glucose homeostasis in female NOD mice. We found that continuous supplementation of L-serine reduces diabetes incidence and insulitis score. In addition, L-serine treated mice had an improved glucose tolerance test, reduced HOMA-IR, and reduced blood glucose levels...
2018: PloS One
Aurore Quinault, Corinne Leloup, Geoffrey Denwood, Coralie Spiegelhalter, Marianne Rodriguez, Philippe Lefebvre, Nadia Messaddeq, Quan Zhang, Catherine Dacquet, Luc Pénicaud, Stephan C Collins
The rhythmic nature of insulin secretion over the 24h cycle in pancreatic islets has been mostly investigated using transcriptomics studies showing that modulation of insulin secretion over this cycle is achieved via distal stages of insulin secretion. We set out to measure β-cell exocytosis using in depth cell physiology techniques at several time points. In agreement with the activity and feeding pattern of nocturnal rodents, we find that C57/Bl6J islets in culture for 24h exhibit higher insulin secretion during the corresponding dark phase than in the light phase (Zeitgeber Time ZT20 and ZT8, respectively, in vivo)...
2018: PloS One
David Vrana, Viktor Hlavac, Veronika Brynychova, Radka Vaclavikova, Cestmir Neoral, Jiri Vrba, Rene Aujesky, Marcel Matzenauer, Bohuslav Melichar, Pavel Soucek
The prognosis of esophageal cancer (EC) is poor, despite considerable effort of both experimental scientists and clinicians. The tri-modality treatment consisting of neoadjuvant chemoradiation followed by surgery has remained the gold standard over decades, unfortunately, without significant progress in recent years. Suitable prognostic factors indicating which patients will benefit from this tri-modality treatment are missing. Some patients rapidly progress on the neoadjuvant chemoradiotherapy, which is thus useless and sometimes even harmful...
March 15, 2018: International Journal of Molecular Sciences
Blanca De Unamuno, Zaida García-Casado, José Bañuls, Celia Requena, José Antonio Lopez-Guerrero, Eduardo Nagore
CDKN2A germline mutations increase the risk of melanoma development and are present in 20 and 10% of familial and multiple melanoma cases, respectively. Pancreatic cancer has been associated with CDKN2A in some populations and, accordingly, its presence in first-degree or second-degree relatives of a melanoma patient is considered as a criterion for genetic testing. In this study, we show that in an area with low melanoma incidence, CDKN2A germline mutations in patients with melanoma and personal or family history of pancreatic cancer are mainly present in the setting of familial or multiple melanoma cases...
March 14, 2018: Melanoma Research
Anne Munck, Rym Boulkedid, Laurence Weiss, Pierre Foucaud, Nathalie Wizla-Derambure, Philippe Reix, François Bremont, Jocelyne Derelle, Julien Schroedt, Corinne Alberti
OBJECTIVE: To evaluate nutritional status and associated factors in a cystic fibrosis (CF) cohort diagnosed by newborn screening and followed up to month 24. METHODS: A prospective longitudinal multicenter study assessing nutritional status according to pancreatic status, feeding modalities, prescriptions, pulmonary outcome and biological nutritional parameters. RESULTS: One-hundred-and-five infants were recruited and 99 completed the study...
March 14, 2018: Journal of Pediatric Gastroenterology and Nutrition
Gabriel Carvajal, Denis Dupoiron, Valerie Seegers, Nathalie Lebrec, François Boré, Pierre-Yves Dubois, Damien Leblanc, Thierry Delorme, Sabrina Jubier-Hamon
BACKGROUND: Pancreatic cancer is the fourth leading cause of cancer-related death in Europe and the United States. Studies have demonstrated that patients with pancreatic cancer have a high prevalence of pain, with rates varying from 47% to 82%. Analgesia using intrathecal drug delivery systems (IDDS) has been poorly studied specifically in this population. METHODS: The IDDS for pancreatic cancer pain was a follow-up observational study designed to evaluate 11-year results of IDDS for refractory pancreatic cancer pain at the Institut de Cancérologie de L'Ouest, Paul Papin in France...
March 14, 2018: Anesthesia and Analgesia
Christopher J Halbrook, Marina Pasca di Magliano, Costas A Lyssiotis
In the event of an injury, normal tissues exit quiescent homeostasis and rapidly engage a complex stromal and immune program. These tissue repair responses are hijacked and become dysregulated in carcinogenesis to form a growth supportive tumor microenvironment. In pancreatic ductal adenocarcinoma (PDA), which remains one of the deadliest major cancers, the microenvironment is a key driver of tumor maintenance that impedes many avenues of therapy. In this review, we outline recent efforts made to uncover the microenvironmental crosstalk mechanisms which support pancreatic cancer cells, and detail the strategies which have been undertaken to help overcome these barriers...
March 15, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
Teklab Gebregiworgis, Christopher Boyd Marshall, Tadateru Nishikawa, Nikolina Radulovich, María-José Sandi, Zhenhao Fang, Robert Rottapel, Ming-Sound Tsao, Mitsuhiko Ikura
Small GTPases (sGTPases) are critical switch-like regulators that mediate several important cellular functions and are often mutated in human cancers. They are activated by guanine nucleotide exchange factors (GEFs), which specifically catalyze the exchange of GTP for GDP. GEFs coordinate signaling networks in normal cells, and are frequently deregulated in cancers. sGTPase signaling pathways are complex and interconnected; however, most GEF assays do not reveal such complexity. In this communication, we describe the development of a unique real-time NMR-based multiplexed GEF assay that employs distinct isotopic labeling schemes for each sGTPase protein to enable simultaneous observation of six proteins of interest...
March 15, 2018: Journal of the American Chemical Society
Kapo Saukkonen, Jaana Hagström, Harri Mustonen, Laura Lehtinen, Olli Carpen, Leif C Andersson, Hanna Seppänen, Caj Haglund
Expression of regenerating islet-derived protein 4 (REG4), a secretory protein involved in cell differentiation and proliferation, is upregulated in inflammatory bowel diseases and in many gastrointestinal malignancies. The prognostic significance of its expression in pancreatic ductal adenocarcinoma is unknown. Our aim was to investigate tumor tissue and serum REG4 expression in pancreatic ductal adenocarcinoma patients. We also evaluated as a control the diagnostic value of serum REG4 level in patients with chronic pancreatitis...
March 2018: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
M J Yang, J H Kim, D J Kim, J C Hwang, B M Yoo
No abstract text is available yet for this article.
April 2018: Journal of Gastroenterology and Hepatology
D Sunjaya, J Jacobi, S Sweetser
No abstract text is available yet for this article.
April 2018: Journal of Gastroenterology and Hepatology
M K Kang, T N Kim
No abstract text is available yet for this article.
April 2018: Journal of Gastroenterology and Hepatology
Abraham Neelankal John, Ramesh Ram, Fang-Xu Jiang
Type 2 diabetes (T2D) is a global health issue and dedifferentiation plays underlying causes in the pathophysiology of T2D; however, there is a lack of understanding in the mechanism. Dedifferentiation results from the loss of function of pancreatic β-cells alongside a reduction in essential transcription factors under various physiological stressors. Our study aimed to establish db/db as an animal model for dedifferentiation by using RNA sequencing to compare the gene expression profile in islets isolated from wild-type, db/+ and db/db mice, and qPCR was performed to validate those significant genes...
March 14, 2018: Endocrine Pathology
Federico Pasin, Giulia Tanzi, Roberto Grassia
No abstract text is available yet for this article.
March 14, 2018: Internal and Emergency Medicine
Thierry Almont, Corinne Couteau, Hélène Etienne, Pierre Bondil, Rosine Guimbaud, Leslie Schover, Éric Huyghe
PURPOSE: To assess sexual health and needs for sexology care of cancer patients during chemotherapy. METHODS: We performed a 4-month cross-sectional study in cancer patients treated by chemotherapy in the digestive cancer department of a regional university hospital. Patients were asked to fill out a self-administered questionnaire about their sexual health, Sexual Quality of Life Questionnaire for Male (SQoL-M) or Female (SQoL-F), and their needs for sexology care...
March 14, 2018: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
Daniele Alberti, Laura Righetti, Adrian Bianchi, Gian Luigi de'Angelis, Giovanni Boroni
BACKGROUND: Bowel dilatation is a common adaptive mechanism after intestinal resection. The symptomatic dilated dysmotile duodenum is difficult to manage, since conventional bowel tailoring and lengthening techniques are potentially hazardous because of the anatomy of the duodenal blood supply, the proximity to the pancreas, and the risk of injury to the common bile duct. METHODS: A 2-month-old child with short bowel and a symptomatic massively dilated duodenum was treated with a Transverse Flap Duodenoplasty (TFD)...
March 14, 2018: Pediatric Surgery International
Leticia Moreira, Basil Bakir, Priya Chatterji, Zahra Dantes, Maximilian Reichert, Anil K Rustgi
Pancreatic ductal adenocarcinoma is one of the most aggressive forms of cancer, and the third leading cause of cancer-related mortality in the United States. Although important advances have been made in the last decade, the mortality rate of pancreatic ductal adenocarcinoma has not changed appreciably. This review summarizes a rapidly emerging model of pancreatic cancer research, focusing on 3-dimensional organoids as a powerful tool for several applications, but above all, representing a step toward personalized medicine...
March 2018: Cellular and Molecular Gastroenterology and Hepatology
Hiroto Matsuda, Satoshi Tamada, Minoru Kato, Akira Yamamoto, Taro Iguchi, Tatsuya Nakatani
A 73-year-old woman with chief complaint of macroscopic hematuria was diagnosed as having left renal tumor with pancreatic invasion. Nephrectomy was performed. Pathological diagnosis was clear cell carcinoma, pT3a. Three months after the operation, liver metastasis appeared and sunitinib was started. Most of the liver metastases disappeared; however, a new lesion appeared, and sunitinib was switched to axitinib, which was effective on the residual lesion, but the new lesion had poor response. Transarterial chemoembolization was performed to treat the liver metastases, and all metastatic lesions disappeared...
March 2018: Urology Case Reports
Sameen Khalid, Aamer Abbass, Eric Nellis, Shashin Shah, Hiral Shah
Pancreatic pseudocysts and walled-off pancreatic necrosis arise as a complication of pancreatitis. Multiple fluid collections are seen in 5-20% of the patients who have walled-off peripancreatic fluid collections. There is a paucity of data regarding the role of endoscopic transmural drainage in the management of multiple pancreatic fluid collections. In this case report, we present the case of a 72-year-old male with three walled-off pancreatic fluid collections in the setting of acute necrotizing pancreatitis...
January 9, 2018: Curēus
Kei Kawaguchi, Qinghong Han, Shukuan Li, Yuying Tan, Kentaro Igarashi, Kentaro Miyake, Tasuku Kiyuna, Masuyo Miyake, Bartosz Chemielwski, Scott D Nelson, Tara A Russell, Sarah M Dry, Yunfeng Li, Arun S Singh, Mark A Eckardt, Michiaki Unno, Fritz C Eilber, Robert M Hoffman
An excessive requirement for methionine (MET) for growth, termed MET dependence, appears to be a general metabolic defect in cancer. We have previously shown that cancer-cell growth can be selectively arrested by MET restriction such as with recombinant methioninase (rMETase). In the present study, we utilized patient-derived orthotopic xenograft (PDOX) nude mouse models with pancreatic cancer or melanoma to determine the relationship between intra-tumor MET level and tumor size. After the tumors grew to 100 mm3 , the PDOX nude mice were divided into two groups: untreated control and treated with rMETase (100 units, i...
February 16, 2018: Oncotarget
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