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pancreatitis treatment

Nelson S Yee
Progress has been made in the treatment of gastrointestinal cancers through advances in systemic therapies, surgical interventions, and radiation therapy. At the Multi-Disciplinary Patient Care in Gastrointestinal Oncology conference, the faculty members of the Penn State Health Milton S. Hershey Medical Center presented a variety of topics that focused on this sub-specialty. This conference paper highlights the new development in systemic treatment of various malignant diseases in the digestive system. Results of the recent clinical trials that investigated the clinical efficacy of pegylated hyaluronidase, napabucasin, and L-asparaginase in pancreatic carcinoma are presented...
March 16, 2018: Biomedicines
Sweet Ping Ng, Joseph M Herman
Pancreatic cancer is a devastating disease with poor survival outcomes. Recent studies have shown that the addition of radiotherapy to chemotherapy in the setting of locally advanced pancreatic cancer did not improve overall survival outcome. These studies commonly utilize conventional radiotherapy treatment fractionation and technique (typically 3-D conformal radiotherapy or intensity modulated radiotherapy). Although no clear benefit in overall survival was demonstrated in those studies, those who received radiotherapy did have a clear benefit in terms of local control...
March 16, 2018: Cancers
Katarzyna Skrzypek, Yazmin Brito Barrera, Thomas Groth, Dimitrios Stamatialis
INTRODUCTION: Encapsulation of pancreatic islets or beta cells is a promising strategy for treatment of type 1 diabetes by providing an immune isolated environment and allowing for transplantation in a different location than the liver. However, islets used for encapsulation often show lower functionality due to the damaging of islet endothelial cells during the isolation procedure. Factors produced by endothelial cells have great impact on beta cell insulin secretion. Therefore, mutual signaling between endothelial cells and beta cells should be considered for the development of encapsulation systems to achieve high insulin secretion and maintain beta cell viability...
March 2018: International Journal of Artificial Organs
Mаhmoud Youns, Abeer ElKhoely, Rehab Kamel
Pancreatic cancer, the fourth most common cause of cancer-related deaths, is one of the most aggressive and devastating human malignancies with increasing incidence worldwide. To date, surgical resection is the only potentially curative therapy available for pancreatic cancer patients. Early diagnosis of pancreatic tumors is difficult, and hence, nearly 80% of patients cannot receive surgical resection. Natural products have always been a vital source for novel compounds for cancer treatment. The naturally occurring prenylated xanthone, gambogic acid, has been previously shown to exert potent anticancer, anti-inflammatory, apoptotic, antiangiogenic, and antioxidant activities...
March 15, 2018: Naunyn-Schmiedeberg's Archives of Pharmacology
Lianbin Xu, Xueyan Lin, Robin R White, Mark D Hanigan, Zhiyong Hu, Qiuling Hou, Yun Wang, Zhonghua Wang
Background: Circulating amino acid (AA) and nitric oxide (NO) concentrations and hepatic gluconeogenesis are affected by previous protein intake. However, information about their relations and islet hormone responses is limited. Objective: This study investigated the associations between islet hormone concentrations with circulating AA and NO concentrations as well as with hepatic gluconeogenesis in lactating rats. Methods: At delivery, 18 Wistar rats aged 14 wk were assigned either to low-protein (LP; 9% protein), standard-protein (SP; 21% protein), or high-protein (HP; 35% protein) diets for 15 d in groups of 6 pups/dam...
March 1, 2018: Journal of Nutrition
Muhammad Khairi Ahmad, Nur Ainina Abdollah, Nurul Husna Shafie, Narazah Mohd Yusof, Siti Razila Abdul Razak
Mitogen-activated protein kinases (MAPKs) are the main regulators of cellular proliferation, growth, and survival in physiological or pathological conditions. Aberrant MAPK signaling plays a pivotal role in carcinogenesis, which leads to development and progression of human cancer. Dual-specificity phosphatase 6 (DUSP6), a member of the MAPK phosphatase family, interacts with specifically targeted extracellular signal-regulated kinase 1/2 via negative feedback regulation in the MAPK pathway of mammalian cells...
February 2018: Cancer Biology & Medicine
Verena M Throm, David Männle, Thomas Giese, Andrea S Bauer, Matthias M Gaida, Juergen Kopitz, Thomas Bruckner, Konstanze Plaschke, Svetlana P Grekova, Klaus Felix, Thilo Hackert, Nathalia A Giese, Oliver Strobel
Smoking is associated with increased risk and poorer prognosis of pancreatic ductal adenocarcinoma (PDAC). Nicotine acts through cholinergic nicotinic receptors, preferentially α7 (CHRNA7) that also binds the endogenous ligand SLURP1 (Secreted Ly-6/uPAR-Related Protein 1). The clinical significance of SLURP1 and its interaction with nicotine in PDAC are unclear. We detected similar levels of SLURP1 in sera from healthy donors and patients with chronic pancreatitis or PDAC; higher preoperative values were associated with significantly better survival in patients with resected tumors...
February 20, 2018: Oncotarget
Francesca Vena, Ruochen Jia, Arman Esfandiari, Juan J Garcia-Gomez, Manuel Rodriguez-Justo, Jianguo Ma, Sakeena Syed, Lindsey Crowley, Brian Elenbaas, Samantha Goodstal, John A Hartley, Daniel Hochhauser
Targeting the DNA damage response (DDR) in tumors with defective DNA repair is a clinically successful strategy. The RAS/RAF/MEK/ERK signalling pathway is frequently deregulated in human cancers. In this study, we explored the effects of MEK inhibition on the homologous recombination pathway and explored the potential for combination therapy of MEK inhibitors with DDR inhibitors and a hypoxia-activated prodrug. We studied effects of combining pimasertib, a selective allosteric inhibitor of MEK1/2, with olaparib, a small molecule inhibitor of poly (adenosine diphosphate [ADP]-ribose) polymerases (PARP), and with the hypoxia-activated prodrug evofosfamide in ovarian and pancreatic cancer cell lines...
February 20, 2018: Oncotarget
Meng-Lin Liu, Meng-Long Wang, Jing-Jun Lv, Jie Wei, Jun Wan
Adriamycin (ADR) is a chemotherapeutic drug used to treat tumors in a clinical setting. However, its use is limited by a side effect of cardiotoxicity. Glibenclamide (Gli), an inhibitor of mitochondrial ATP-dependent potassium (K-ATP) channels, blocks the cardioprotective effects of mitochondrial K-ATP channel openers and induces apoptosis in rodent pancreatic islet β-cell lines. However, little is known about the role of Gli in ADR-induced cardiotoxicity. The present study was designed to investigate the impact of Gli on ADR-induced cardiotoxicity in rats...
April 2018: Experimental and Therapeutic Medicine
Jason T C Lee, Iryna Shanina, Yung Ning Chu, Marc S Horwitz, James D Johnson
Pancreatic beta-cells are selectively destroyed by the host immune system in type 1 diabetes. Thus, drugs that preserve beta-cell mass and/or function have the potential to prevent or slow the progression of this disease. We recently reported that the use-dependent sodium channel blocker, carbamazepine, protects beta-cells from inflammatory cytokines in vitro. Here, we tested the effects of carbamazepine treatment in female non-obese diabetic (NOD) mice by supplementing LabDiet 5053 with 0.5% w/w carbamazepine to achieve serum carbamazepine levels of 14...
March 15, 2018: Scientific Reports
Anthony J Kee, Jayshan Chagan, Jeng Yie Chan, Nicole S Bryce, Christine A Lucas, Jun Zeng, Jeff Hook, Herbert Treutlein, D Ross Laybutt, Justine R Stehn, Peter W Gunning, Edna C Hardeman
The development of novel small molecule inhibitors of the cancer-associated tropomyosin 3.1 (Tpm3.1) provides the ability to examine the metabolic function of specific actin filament populations. We have determined the ability of these anti-Tpm (ATM) compounds to regulate glucose metabolism in mice. Acute treatment (1 h) of wild-type (WT) mice with the compounds (TR100 and ATM1001) led to a decrease in glucose clearance due mainly to suppression of glucose-stimulated insulin secretion (GSIS) from the pancreatic islets...
March 15, 2018: Scientific Reports
Georges Al-Helou, Nardos Temesgen, Jonathan Gwizdala, Jalil Ahari
Our patient is a 69-year-old man who presented to the emergency department with left-sided hemiparesis that started 4 hours prior to presentation. Brain CT showed right basal ganglia and internal capsule haemorrhagic strokes. MRI revealed multiple brain lesions suspicious for metastases. Further workup revealed a 5 cm lung mass and a 1 cm pancreatic nodule. Biopsy of both pulmonary and pancreatic lesions was consistent with melanoma and was similar histologically. The patient underwent cyberknife stereotactic radiosurgery to the brain metastases followed by immunotherapy with pembrolizumab, and then by nivolumab and ipilimumab...
March 15, 2018: BMJ Case Reports
Brendan M Everett, Marc Y Donath, Aruna D Pradhan, Tom Thuren, Prem Pais, Jose C Nicolau, Robert J Glynn, Peter Libby, Paul M Ridker
BACKGROUND: Subclinical inflammation mediated in part by interleukin-1 beta (IL-1β) participates in peripheral insulin resistance and impaired pancreatic insulin secretion. OBJECTIVES: We tested the hypothesis that canakinumab, an IL-1β inhibitor, reduces incident diabetes. METHODS: The Canakinumab Antiinflammatory Thrombosis Outcomes Study (CANTOS) randomized 10,061 patients with prior MI and high-sensitivity C-reactive protein (hsCRP) ≥2 mg/L to placebo or canakinumab at doses of 50mg, 150mg, or 300mg subcutaneously once every three months...
March 3, 2018: Journal of the American College of Cardiology
Sabine Salloch, Ina C Otte, Anke Reinacher-Schick, Jochen Vollmann
The impact of patient preferences in evidence-based medicine is a complex issue which touches on theoretical questions as well as medical practice in the clinical context. The interaction between evidence-based recommendations and value-related patient preferences in clinical practice is, however, highly complex and requires not only medical knowledge but social, psychological and communicative competencies on the side of the physician. The multi-layered process of oncology physicians' clinical decision-making was explored in 14 semi-structured interviews with respect to a first diagnosis of a pancreatic adenocarcinoma...
March 12, 2018: Zeitschrift Für Evidenz, Fortbildung und Qualität Im Gesundheitswesen
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
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
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
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
Chaobin He, Yize Mao, Xiangming Lao, Shengping Li, Xiaojun Lin
The neutrophil-to-lymphocyte ratio (NLR) has been regarded as a prognostic factor in various types of cancer. The present study aimed to identify the association between NLR and combined hepatocellular cholangiocarcinoma (cHCC-CC) in patients who underwent surgical resection. The present study retrospectively reviewed 59 patients who were diagnosed with cHCC-CC and treated with surgical resection between January 2000 and October 2014 at the Department of Hepatobiliary and Pancreatic Surgery at Sun Yat-sen University Cancer Center (Guangzhou, China)...
April 2018: Oncology Letters
Zai Wang, Liang Peng, Yu-Li Song, Shiqing Xu, Zhan Hua, Ni Fang, Min Zhai, Honglin Liu, Qing Fang, Tingting Deng, Wenjian Zhang, Yuan-Jia Chen, Jinning Lou
Aberrant blood vessel formation and hemorrhage may contribute to tumor progression and are potential targets in the treatment of several types of cancer. Pancreatic neuroendocrine tumors (PNETs) are highly vascularized, particularly when they are well-differentiated. However, the process of vascularization and endothelial cell detachment in PNETs is poorly understood. In the present study, 132 PNET clinical samples were examined and a special type of hemorrhagic region was observed in ~30% of the samples regardless of tumor subtype...
April 2018: Oncology Letters
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