Genetic Alterations of Periampullary and Pancreatic Ductal Adenocarcinoma: An Overview.

Genetic Alterations of Periampullary and Pancreatic Ductal Adenocarcinoma: An Overview. Curr Genomics. 2018 Sep;19(6):444-463 Authors: Sikdar N, Saha G, Dutta A, Ghosh S, Shrikhande SV, Banerjee S Abstract Pancreatic Ductal AdenoCarcinoma (PDAC) is one of the most lethal malignancies of all solid cancers. Precancerous lesions for PDAC include PanIN, IPMNs and MCNs. PDAC has a poor prognosis with a 5-year survival of approximately 6%. Whereas Periampulary AdenoCarcinoma (PAC) having four anatomic subtypes, pancreatic, Common Bile Duct (CBD), ampullary and duodenum shows relative better prognosis. The highest incidence of PDAC has been reported with black with respect to white population. Similarly, incidence rate of PAC also differs with different ethnic populations. Several lifestyle, environmental and occupational exposures including long-term diabetes, obesity, and smoking, have been linked to PDAC, however, for PAC the causal risk factors were poorly described. It is now clear that PDAC and PAC are a multi-stage process resulting from the accumulation of genomic alterations in the somatic DNA of normal cells as well as inherited mutations. Approximately 10% of PDAC have a familial inheritance. Germline mutations in CDKN2A, BRCA2, STK11, PALB2, PRSS1, etc., as well as certain syndromes have been well associated with predisposition to PDAC. KRAS, CDKN2A, TP53 and SMAD4 are the 4 "mountains" (high-frequency driver genes) which have been known to...
Source: Current Genomics - Category: Genetics & Stem Cells Tags: Curr Genomics Source Type: research

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Alessandro Poggi1*, Roberto Benelli2, Roberta Venè1, Delfina Costa1, Nicoletta Ferrari1, Francesca Tosetti1 and Maria Raffaella Zocchi3 1Molecular Oncology and Angiogenesis Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy 2Immunology Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy 3Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy It is well established that natural killer (NK) cells are involved in both innate and adaptive immunity. Indeed, they can recognize molecules induced at the cell surface by stress signals ...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Conclusion and Perspectives The IL-6/JAK/STAT signaling cascade plays a dominant role in skeletal muscle pathophysiology. IL-6 autocrine, paracrine, and endocrine functions assign to its downstream effectors pivotal importance in skeletal muscle-wasting-associated diseases and other multiple system diseases where muscle acts in communication with other organs. Targeting the components of the JAK/STAT pathway recently emerged as a strategic approach for the treatment of inflammatory diseases and human cancer. This review highlights the opposite outcomes on muscle biology caused by the amount of local and systemic release ...
Source: Frontiers in Physiology - Category: Physiology Source Type: research
Abstract Pancreatic ductal adenocarcinoma (PDAC) remains a deadly disease with no efficacious treatment options. PDAC incidence is projected to increase, which may be caused at least partially by the obesity epidemic. Significantly enhanced efforts to prevent or intercept this cancer are clearly warranted. Oncogenic KRAS mutations are recognized initiating events in PDAC development, however, they are not entirely sufficient for the development of fully invasive PDAC. Additional genetic alterations and/or environmental, nutritional, and metabolic signals, as present in obesity, type-2 diabetes mellitus, and inflam...
Source: World Journal of Gastroenterology : WJG - Category: Gastroenterology Authors: Tags: World J Gastroenterol Source Type: research
Siriluck Ponsuksili1, Nares Trakooljul1, Frieder Hadlich1, Karen Methling2, Michael Lalk2, Eduard Murani1 and Klaus Wimmers1,3* 1Leibniz Institute for Farm Animal Biology (FBN), Institute for Genome Biology, Functional Genome Analysis Research Unit, Dummerstorf, Germany 2Institute for Biochemistry – Metabolomics, University of Greifswald, Greifswald, Germany 3Faculty of Agricultural and Environmental Sciences, University of Rostock, Rostock, Germany Given the central metabolic role of the liver, hepatic metabolites and transcripts reflect the organismal physiological state. Biochemical-clinical plasma bio...
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
This study aimed to contribute to the need of finding new and more effective bioactive molecules against several of the earlier mentioned threats faced by human kind nowadays. For this, eighteen species from the Actinomycetales previously isolated from Erylus spp. sponges collected in Portuguese marine waters (Açores, Madeira, and continental shelf) were screened for antimicrobial, anti-cancer, anti-parasitic and anti-obesogenic activities. Materials and Methods Biological Material The bacteria under study belong to the order Actinomycetales within the phylum Actinobacteria and were isolated from marine sponges o...
Source: Frontiers in Microbiology - Category: Microbiology Source Type: research
rio F Abstract The most frequent pancreatic cancer is pancreatic adenocarcinoma. It has high and early locally and distant invasiveness; this is the reason why it often shows little sign or symptoms in early stage and poor prognosis after the diagnosis, frequently in advanced stage. Although it is possible to detect this tumor in early stage because of its neoplastic precursor (PanINs). Epidemiological data shows that pancreatic cancer is not very common but obvious it is one of the most neoplastic death-cause in the world. The trend of incidence is quite increasing through years, proportionally to the increase of...
Source: Acta Bio-Medica : Atenei Parmensis - Category: General Medicine Authors: Tags: Acta Biomed Source Type: research
Introduction: Type 2 diabetes mellitus is likely the third modifiable risk factor for pancreatic cancer (PDAC) after cigarette smoking and obesity. Epidemiological investigations have found that long-term type 2 diabetes mellitus is associated with a 1.5- to 2.0-fold increase in the risk of PDAC. On the other hand, new-onset diabetes may indicate subclinical PDAC, and patients with new-onset diabetes may constitute a population in whom PDAC can be detected early. Use of the antidiabetic drugs, such as metformin, has been associated with reduced risk of PDAC in diabetics and recognized as an antitumor agent with the potenti...
Source: Annals of Oncology - Category: Cancer & Oncology Source Type: research
Objectives Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with virtually no efficacious treatments. Chronic conditions such as obesity and type-2 diabetes are known risk factors, thus making PDAC amenable for preventive strategies. Metformin, a widely used anti-diabetic drug shown to improve metabolic dysfunction, has been linked epidemiologically with reduced incidence, recurrence and mortality of cancer in diabetic patients. However, the efficacy and mechanisms of metformin in obesity-promoted PDAC are much less known.
Source: Pancreatology - Category: Gastroenterology Authors: Tags: 7. Experimental pancreatic cancer II Source Type: research
A workshop on “The Interface of Pancreatic Cancer with Diabetes, Obesity, and Inflammation: Research Gaps and Opportunities” was held by the National Institute of Diabetes and Digestive and Kidney Diseases on October 12, 2017. The purpose of the workshop was to explore the relationship and possible mechanisms of the increased risk of pancreatic ductal adenocarcinoma (PDAC) related to diabetes, the role of altered intracellular energy metabolism in PDAC, the mechanisms and biomarkers of diabetes caused by PDAC, the mechanisms of the increased risk of PDAC associated with obesity, and the role of inflammatory eve...
Source: Pancreas - Category: Gastroenterology Tags: Conference Reports Source Type: research
Abstract Diabetes is an established risk factor for pancreatic cancer (PaC), together with obesity, Western diet and tobacco smoking. The common mechanistic link might be the accumulation of advanced glycation endproducts (AGEs), which characterizes all the above disease conditions and unhealthy habits. Surprisingly, however, the role of AGEs in PaC has not been examined yet, despite the evidence of a tumor‐promoting role of RAGE, the receptor for AGEs. Here, we tested the hypothesis that AGEs promote PaC through RAGE activation. To this end, we investigated the effects of the AGE Nε‐carboxymethyllysine (CML) i...
Source: The Journal of Pathology - Category: Pathology Authors: Tags: Original Paper Source Type: research
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