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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/28646417/mesenchymal-stem-cell-therapy-for-acute-and-chronic-pancreatitis
#2
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/28646282/surgery-for-pancreatic-ductal-adenocarcinoma
#3
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/28645526/injury-induced-gp130-cytokine-signaling-in-peripheral-ganglia-is-reduced-in-diabetes-mellitus
#4
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
#5
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/28643979/-acute-pancreatitis-new-aspects-for-the-management
#6
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/28643741/prognostic-and-predictive-markers-of-response-to-treatment-in-patients-with-locally-advanced-unresectable-and-metastatic-pancreatic-adenocarcinoma-treated-with-gemcitabine-nab-paclitaxel-results-of-a-retrospective-analysis
#7
Ana Fernández Montes, Paula González Villarroel, Manuel Valladares Ayerbes, Juan De la Cámara Gómez, Guillermo Quintero Aldana, Lidia Vázquez Tuñas, Mercedes Salgado Fernández, Mónica Jorge Fernández
BACKGROUND: Recent studies support the use of gemcitabine and nab-paclitaxel in adults with locally advanced unresectable or metastatic pancreatic adenocarcinoma although insufficient data are available on prognostic and predictive markers of response to treatment. OBJECTIVE: The objective of this study is to identify treatment response markers in patients with locally advanced unresectable or metastatic pancreatic adenocarcinoma. MATERIALS AND METHODS: This is an observational, retrospective, and multicenter study...
April 2017: Journal of Cancer Research and Therapeutics
https://www.readbyqxmd.com/read/28642461/the-ca19-9-and-sialyl-tra-antigens-define-separate-subpopulations-of-pancreatic-cancer-cells
#8
Daniel Barnett, Ying Liu, Katie Partyka, Ying Huang, Huiyuan Tang, Galen Hostetter, Randall E Brand, Aatur D Singhi, Richard R Drake, Brian B Haab
Molecular markers to detect subtypes of cancer cells could facilitate more effective treatment. We recently identified a carbohydrate antigen, named sTRA, that is as accurate a serological biomarker of pancreatic cancer as the cancer antigen CA19-9. We hypothesized that the cancer cells producing sTRA are a different subpopulation than those producing CA19-9. The sTRA glycan was significantly elevated in tumor tissue relative to adjacent pancreatic tissue in 3 separate tissue microarrays covering 38 patients...
June 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28642332/morphine-worsens-the-severity-and-prevents-pancreatic-regeneration-in-mouse-models-of-acute-pancreatitis
#9
Usman Barlass, Raini Dutta, Hassam Cheema, John George, Archana Sareen, Ajay Dixit, Zuobiao Yuan, Bhuwan Giri, Jingjing Meng, Santanu Banerjee, Sulagna Banerjee, Vikas Dudeja, Rajinder K Dawra, Sabita Roy, Ashok K Saluja
BACKGROUND: Opioids such as morphine are widely used for the management of pain associated with acute pancreatitis. Interestingly, opioids are also known to affect the immune system and modulate inflammatory pathways in non-pancreatic diseases. However, the impact of morphine on the progression of acute pancreatitis has never been evaluated. In the current study, we evaluated the impact of morphine on the progression and severity of acute pancreatitis. METHODS: Effect of morphine treatment on acute pancreatitis in caerulein, L-arginine and ethanol-palmitoleic acid models was evaluated after induction of the disease...
June 22, 2017: Gut
https://www.readbyqxmd.com/read/28642056/can-stem-cells-ameliorate-the-pancreatic-damage-induced-by-streptozotocin-in-rats
#10
Amira Ragab El Barky, Amany Abdel Hamid Ezz, Abeer Abd-Elhameed Alm-Eldeen, Samy Ali Hussein, Yehia Ahmed Hafez, Tarek Mostafa Mohamed
BACKGROUND: Stem cell therapy holds great promise for the repair of injured tissues and organs, and it is one of the most promising therapies for diabetes mellitus. Therefore, the present study was undertaken to elucidate the antidiabetic effect of both mesenchymal stem cells (MSCs) and insulin-producing cells (IPCs) on streptozotocin (STZ)-induced diabetes in rats. MATERIALS AND METHODS: MSCs were derived from bone marrow of male albino rats. MSCs were characterized morphologically and by Cluster of differentiation (CD(-ve34)) and (CD(+ve105))...
June 19, 2017: Canadian Journal of Diabetes
https://www.readbyqxmd.com/read/28641307/human-equilibrative-nucleoside-transporter-1-gene-expression-is-associated-with-gemcitabine-efficacy-in-advanced-leiomyosarcoma-and-angiosarcoma
#11
Bruno Vincenzi, Silvia Stacchiotti, Paola Collini, Francesco Pantano, Carla Rabitti, Giuseppe Perrone, Michele Iuliani, Alfonso Baldi, Giuseppe Badalamenti, Roberta Sanfilippo, Daniele Santini, Andrea Onetti Muda, Alessandro Gronchi, Paolo Casali, Angelo Paolo Dei Tos, Giuseppe Tonini
BACKGROUND: The expression of human equilibrative nucleoside transporter 1 (hENT1), the major gemcitabine transporter into cells, has been thoroughly investigated as a predictive marker of response to gemcitabine in pancreatic cancer and biliary tract cancers. Since gemcitabine is widely used in the treatment of leiomyosarcoma and angiosarcoma, we investigated the correlation between hENT1 expression and gemcitabine efficacy in these sarcoma subtypes. METHODS: We retrospectively identified 71 patients affected by advanced angiosarcoma (26) or leiomyosarcoma (45) treated within five Italian referral centres for sarcoma; among them, 49 patients (15 angiosarcoma, 34 leiomyosarcoma) were treated with gemcitabine...
June 22, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28640192/pancreatic-ductal-adenocarcinoma-current-and-evolving-therapies
#12
REVIEW
Aleksandra Adamska, Alice Domenichini, Marco Falasca
Pancreatic ductal adenocarcinoma (PDAC), which constitutes 90% of pancreatic cancers, is the fourth leading cause of cancer-related deaths in the world. Due to the broad heterogeneity of genetic mutations and dense stromal environment, PDAC belongs to one of the most chemoresistant cancers. Most of the available treatments are palliative, with the objective of relieving disease-related symptoms and prolonging survival. Currently, available therapeutic options are surgery, radiation, chemotherapy, immunotherapy, and use of targeted drugs...
June 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28639885/microrna-195-inhibits-the-proliferation-and-invasion-of-pancreatic-cancer-cells-by-targeting-the-fatty-acid-synthase-wnt-signaling-pathway
#13
Zhichao Xu, Chunli Li, Hui Qu, Huiling Li, Qiaoyan Gu, Jing Xu
Emerging evidence suggests that microRNAs are critical regulators of cancer development and progression. MicroRNA-195 has been reported as a cancer-related microRNA in many human cancers. However, the role of microRNA-195 in pancreatic cancer remains largely unknown. Here, we show that microRNA-195 is downregulated in pancreatic cancer tissues and cell line. Also, we show that overexpression of microRNA-195 inhibits the proliferation and invasion of pancreatic cancer cells, whereas suppression of microRNA-195 promotes proliferation and invasion...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28639695/glycogen-synthase-kinase-3%C3%AE-ablation-limits-pancreatitis-induced-acinar-to-ductal-metaplasia
#14
Li Ding, Geou-Yarh Liou, Daniel M Schmitt, Peter Storz, Jin-San Zhang, Daniel D Billadeau
Acinar-to-ductal metaplasia (ADM) is a reversible epithelial trans-differentiation process that occurs in the pancreas in response to acute inflammation. ADM can rapidly progress toward pre-malignant pancreatic intraepithelial neoplasia (PanIN) lesions in the presence of mutant KRas and ultimately pancreatic adenocarcinoma (PDAC). In the present work we elucidate the role and related mechanism of glycogen synthase kinase-3beta (GSK-3β) in ADM development using in vitro 3D cultures and genetically engineered mouse models...
June 22, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28639199/treatment-of-pancreatic-cancer-by-aptamer-conjugated-c-ebp%C3%AE-sarna
#15
Sorah Yoon, John J Rossi
Pancreatic cancer is estimated to become the second-leading cause of cancer-related mortality by 2020. While the death rates of most other cancers continue to decline recently, the death rates of pancreatic cancer are still increasing, with less than 5% of patients achieving 5-year survival. Despite great efforts to improve treatment with combinational therapies in pancreatic cancer patients, limited progress has been made. V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) has been depicted as a therapeutic target in pancreatic cancer for many years...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28639051/adjuvant-treatment-for-pancreatic-ductal-carcinoma
#16
REVIEW
T Macarulla, T Fernández, M E Gallardo, O Hernando, A M López, M Hidalgo
Pancreatic ductal adenocarcinoma (PDAC) is a tumor with a very poor prognosis. Most of the patients are diagnosed in advanced stages of the disease, and 5-year survival rates in these patients remains <10%. Surgery still remains the only radical treatment option, although only 15-20% of patients are candidates for surgical resection at the time of the diagnosis. Patients who undergo radical surgery still have a limited survival rate, being the average of 23 months. Three clinical trials have shown that adjuvant chemotherapy therapy after surgery may improve survival: CONKO-1, ESPAC-3, and ESPAC-4...
June 21, 2017: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/28638801/pancreatic-neuroendocrine-tumor-grade-1-patients-followed-up-without-surgery-case-series
#17
Mitsuru Sugimoto, Tadayuki Takagi, Rei Suzuki, Naoki Konno, Hiroyuki Asama, Ko Watanabe, Jun Nakamura, Hitomi Kikuchi, Yuichi Waragai, Mika Takasumi, Satoshi Kawana, Yuko Hashimoto, Takuto Hikichi, Hiromasa Ohira
Among the three grades of neuroendocrine tumors (NETs), the prognosis for Grade 1 (G1) with surgery is very good. Therefore, we evaluated the prognoses of pancreatic NET (PNET) G1 patients without surgery. A total of 8 patients who were diagnosed with NET G1, with an observation period of more than 6 mo until surgery or without surgery, were recruited. The patients who underwent surgery were ultimately diagnosed using specimens obtained during the surgery, whereas the patients who did not undergo surgery were diagnosed using specimens obtained by endoscopic ultrasonography-guided fine needle aspiration...
June 10, 2017: World Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28638792/immunotherapy-in-pancreatic-cancer-unleash-its-potential-through-novel-combinations
#18
REVIEW
Songchuan Guo, Merly Contratto, George Miller, Lawrence Leichman, Jennifer Wu
Pancreatic cancer is the third leading cause of cancer mortality in both men and women in the United States, with poor response to current standard of care, short progression-free and overall survival. Immunotherapies that target cytotoxic T lymphocyte antigen-4, programmed cell death protein-1, and programmed death-ligand 1 checkpoints have shown remarkable activities in several cancers such as melanoma, renal cell carcinoma, and non-small cell lung cancer due to high numbers of somatic mutations, combined with cytotoxic T-cell responses...
June 10, 2017: World Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28638573/acute-intermittent-porphyria-a-test-of-clinical-acumen
#19
Rashmi Dhital, Sijan Basnet, Dilli Ram Poudel, Khema Raj Bhusal
Acute intermittent porphyria (AIP) is a rare autosomal dominant hepatic porphyria due to deficiency of hydroxymethylbilane synthase (HMBS), also known as porphobilinogen deaminase leading to accumulation of porphyrin precursors. However, gene defect alone is usually not sufficient to cause an acute attack, and many extrinsic factors play a role. Diagnostic tests are defined, but clinical suspicion is often delayed as symptoms mimic other common conditions. We report a case of a 18-year-old male with severe, persistent, and generalized abdominal pain along with marked hyponatremia, with subsequent development of altered mentation needing intensive care...
March 2017: Journal of Community Hospital Internal Medicine Perspectives
https://www.readbyqxmd.com/read/28638216/role-of-surgery-in-pancreatic-cancer
#20
EDITORIAL
Trond A Buanes
Treatment of pancreatic cancer is multimodal and surgery is an essential part, mandatory for curative potential. Also chemotherapy is essential, and serious postoperative complications or rapid disease progression may preclude completion of multimodal treatment. The sequence of treatment interventions has therefore become an important concern, and numerous ongoing randomized controlled trials compare clinical outcome after upfront surgery and neoadjuvant treatment with subsequent resection. In previous years, borderline resectable and locally advanced pancreatic cancer was most often considered unresectable...
June 7, 2017: World Journal of Gastroenterology: WJG
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