Selective phytochemicals targeting pancreatic stellate cells as new anti-fibrotic agents for chronic pancreatitis and pancreatic cancer

Publication date: Available online 14 November 2019Source: Acta Pharmaceutica Sinica BAuthor(s): Puvanesswaray Ramakrishnan, Wei Mee Loh, Subash C.B. Gopinath, Srinivasa Reddy Bonam, Ismail M. Fareez, Rhanye Mac Guad, Maw Shin Sim, Yuan Seng WuAbstractActivated pancreatic stellate cells (PSCs) have been widely accepted as a key precursor of excessive pancreatic fibrosis, which is a crucial hallmark of chronic pancreatitis (CP) and its formidable associated disease, pancreatic cancer (PC). Hence, anti-fibrotic therapy has been identified as a novel therapeutic strategy for treating CP and PC by targeting PSCs. Most of the anti-fibrotic agents have been limited to phase I/II clinical trials involving vitamin analogs, which are abundant in medicinal plants and have proved to be promising for clinical application. The use of phytomedicines, as new anti-fibrotic agents, has been applied to a variety of complementary and alternative approaches. The aim of this review was to present a focused update on the selective new potential anti-fibrotic agents, including curcumin, resveratrol, rhein, emodin, green tea catechin derivatives, metformin, eruberin A, and ellagic acid, in combating PSC in CP and PC models. It aimed to describe the mechanism(s) of the phytochemicals used, either alone or in combination, and the associated molecular targets. Most of them were tested in PC models with similar mechanism of actions, and curcumin was tested intensively. Future research may explore the is...
Source: Acta Pharmaceutica Sinica B - Category: Cancer & Oncology Source Type: research

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Nature Reviews Gastroenterology &Hepatology, Published online: 06 December 2019; doi:10.1038/s41575-019-0242-7An area of research suggests a role for microbiota in the pathogenesis of pancreatic diseases, such as pancreatitis, pancreatic cancer and type 1 diabetes mellitus. In this Perspectives, the authors examine the literature implicating microorganisms in diseases of the pancreas as well as the evidence of an inherent pancreatic microbiota.
Source: Nature Reviews Gastroenterology and Hepatology - Category: Gastroenterology Authors: Source Type: research
ConclusionsPancreatic cancer patients with acute pancreatitis diagnosed up to 90 days before cancer diagnosis had earlier stage at diagnosis and better survival than patients without acute pancreatitis.
Source: Cancer Epidemiology - Category: Cancer & Oncology Source Type: research
ConclusionsKnowledge of pancreatic surgery and management of possible complications ought to be present in the oncologic-gynecologic armamentarium. All patients should be referred to specialized, dedicated, tertiary centers in order to reduce, promptly recognize and optimally manage complications.
Source: European Journal of Surgical Oncology (EJSO) - Category: Surgery Source Type: research
AbstractDipeptidyl peptidase (DPP) ‐4 inhibitors, a class of oral hypoglycemic agents, are widely used, especially in Asian populations, as they have been shown to be well‐tolerated and to cause relatively few hypoglycemic events despite exerting a potent glucose‐lowering effect by promoting endogenous insulin secretion, beside s also having extra‐pancreatic effects. Meanwhile, use of DPP‐4 inhibitors has been reported to be associated with the development of bullous pemphigoid (BP), a rare autoimmune blistering skin disease1, even though the absolute increase in the risk of development of BP is relatively low.
Source: Journal of Diabetes Investigation - Category: Endocrinology Authors: Tags: Commentary Source Type: research
Conclusions: The predictive value of FiCE for pancreatic cancer prevalence was 47%. Histological confirmation with pancreatic juice cytology is necessary before surgical resection. PMID: 31744269 [PubMed - as supplied by publisher]
Source: Clinical Endoscopy - Category: Gastroenterology Tags: Clin Endosc Source Type: research
Pancreatic exocrine insufficiency occurs when there is insufficient production or delivery of pancreatic enzymes required for the digestion and absorption of food. It is associated with relatively poor outcomes, including reduced quality of life and survival.1 Common causes are cancer of the head/body of the pancreas, chronic pancreatitis, pancreatic resection and cystic fibrosis. It can occur following duodenectomy, gastrectomy or untreated coeliac disease via a reduction in cholecystokinin and thereby post-prandial pancreatic stimulation.
Source: Journal of Pain and Symptom Management - Category: Palliative Care Authors: Source Type: research
Authors: Brennan GT, Saif MW Abstract Pancreatic enzyme replacement therapy is safe and effective at treating pancreatic exocrine insufficiency. There are multiple causes of pancreatic exocrine insufficiency including chronic pancreatitis, cystic fibrosis and pancreatic cancer. Testing fecal elastase-1 level is useful for the diagnosis of pancreatic exocrine insufficiency. Starting doses of pancreatic enzyme replacement therapy should be at least 30-40,000 IU with each meal and 15-20,000 IU with snacks. pancreatic enzyme replacement therapy should be taken in divided doses throughout meals. Patients who do not resp...
Source: Journal of the Pancreas - Category: Gastroenterology Tags: JOP Source Type: research
Currently, an effective targeted therapy for pancreatitis is lacking. Hereditary pancreatitis (HP) is a heritable, autosomal-dominant disorder with recurrent acute pancreatitis (AP) progressing to chronic pancreatitis (CP) and a markedly increased risk of pancreatic cancer. In 1996, mutations in PRSS1 were linked to the development of HP. Here, we developed a mouse model by inserting a full-length human PRSS1R122H gene, the most commonly mutated gene in human HP, into mice. Expression of PRSS1R122H protein in the pancreas markedly increased stress signaling pathways and exacerbated AP. After the attack of AP, all PRSS1R122...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
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Source: Contemporary Clinical Trials - Category: Radiology Authors: Source Type: research
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Source: Neoplasia - Category: Cancer & Oncology Authors: Tags: Neoplasia Source Type: research
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