Essential Role of Lyn in Fibrosis.

Fibrotic disorders involve replacement of normal parenchyma with myofibroblasts, which deposit connective tissue, leading to obliteration of the function of the underlying organ. The treatment options are inadequate and reflect the fact that signaling targets in myofibroblasts are unknown. Here we identify the hyperactive Lyn signaling in myofibroblasts of patients with chronic pancreatitis-induced fibrosis. Lyn activation coexpress with markers of activated myofibroblasts, and is increased ~11-fold in chronic pancreatitis compared to normal tissue. Inhibition of Lyn with siRNA or INNO-406 leads to the substantial decrease of migration and proliferation of human chronic pancreatitis myofibroblasts in vitro, while leaving migration and proliferation of normal myofibroblasts only slightly affected. Furthermore, inhibition of Lyn prevents synthesis of procollagen and collagen in myofibroblasts in a mouse model of chronic pancreatitis-induced fibrosis. We conclude that Lyn, as a positive regulator of myofibroblast migration, proliferation, and collagen production, is a key target for preventing fibrosis

Customer churn detection system: Identifying customers who wish to leave a merchant

Abstract. Identifying customers with a higher probability to leave a merchant (churn customers) is a challenging task for sellers. In this paper, we propose a system able to detect churner behavior and to assist merchants in delivering special offers to their churn customers. Two main goals lead our work: on the one hand, the definition of a classifier in order to perform churn analysis and, on the other hand, the definition of a framework that can be enriched with social information supporting the merchant in performing marketing actions which can reduce the probability of losing those customers. Experimental results of an artificial and a real datasets show an increased value of accuracy of the classification when random forest or decision tree are considered

Searching optimal product bundles by means of GA-based Engine and Market Basket Analysis

The product bundling problem is a challenging task in the e-Commerce domain. We propose a generative engine in order to find the bundle of products that best satisfies user requirements and, at the same time, seller needs such as the minimization of the dead stocks and the maximization of net income. The proposed system named Intelligent Bundle Suggestion and Generation (IBSAG) is designed in order to satisfy these requirements. Market Basket Analysis supports the system in user requirement elicitation task. Experimental results prove the ability of the system in finding the optimal tradeoff between different and conflicting constraints

Phosphatidylinositol 3-Kinase

Even though a strong association between inflammation and cancer has been widely accepted, the underlying precise molecular mechanisms are still largely unknown. A complex signaling network between tumor and stromal cells is responsible for the infiltration of inflammatory cells into the cancer microenvironment. Tumor stromal cells such as pancreatic stellate cells (PSCs) and immune cells create a microenvironment that protects cancer cells through a complex interaction, ultimately facilitating their local proliferation and their migration to different sites. Furthermore, PSCs have multiple functions related to local immunity, angiogenesis, inflammation, and fibrosis. Recently, many studies have shown that members of the phosphoinositol-3-phosphate kinase (PI3K) family are activated in tumor cells, PSCs, and tumor-infiltrating inflammatory cells to promote cancer growth. Proinflammatory cytokines and chemokines secreted by immune cells and fibroblasts within the tumor environment can activate the PI3K pathway both in cancer and inflammatory cells. In this review, we focus on the central role of the PI3K pathway in regulating the cross talk between immune/stromal cells and cancer cells. Understanding the role of the PI3K pathway in the development of chronic pancreatitis and cancer is crucial for the discovery of novel and efficacious treatment options

A 5-Year Experience of Benign Pancreatic Hyperenzymemia

OBJECTIVE: Benign pancreatic hyperenzymemia is characterized by a long-term increase of serum pancreatic enzymes in otherwise healthy subjects. This study was designed to determine (a) whether all pancreatic enzymes are elevated, (b) the extent of each enzyme increase, (c) the relative frequency of the familial form, and (d) the relative frequencies of pancreatic and salivary hyperamylasemia and macroamylasemia. METHODS: Two hundred seven asymptomatic subjects with benign pancreatic hyperenzymemia were studied during the 5-year period. Serum amylase, isoamylase, and lipase levels were assessed by immunoenzymatic assays. RESULTS: Most (n = 183; 88.4%) patients had benign pancreatic hyperenzymemia; 155 (74.9%) patients had an abnormal increase of all 3 enzymes, 15 (7.2%) patients of only lipase, and 13 (6.3%) patients of only amylase and pancreatic isoamylase. Lipase levels were the highest (1.1-21 times above upper limit). Of the 183 subjects, 72 were members of 35 different families, 15 (7.2%) had increased salivary amylase, and 9 (4.3%) had macroamylasemia. Wide day-to-day fluctuations of pancreatic enzymes, including falls within the reference ranges, were recorded. CONCLUSIONS: All enzymes were increased in benign pancreatic hyperenzymemia, with lipase showing the highest elevation. Doctors should reassure patients about the benign nature of this condition and limit repeating useless examinations

A 5-Year Experience of Benign Pancreatic Hyperenzymemia

OBJECTIVE: Benign pancreatic hyperenzymemia is characterized by a long-term increase of serum pancreatic enzymes in otherwise healthy subjects. This study was designed to determine (a) whether all pancreatic enzymes are elevated, (b) the extent of each enzyme increase, (c) the relative frequency of the familial form, and (d) the relative frequencies of pancreatic and salivary hyperamylasemia and macroamylasemia. METHODS: Two hundred seven asymptomatic subjects with benign pancreatic hyperenzymemia were studied during the 5-year period. Serum amylase, isoamylase, and lipase levels were assessed by immunoenzymatic assays. RESULTS: Most (n = 183; 88.4%) patients had benign pancreatic hyperenzymemia; 155 (74.9%) patients had an abnormal increase of all 3 enzymes, 15 (7.2%) patients of only lipase, and 13 (6.3%) patients of only amylase and pancreatic isoamylase. Lipase levels were the highest (1.1-21 times above upper limit). Of the 183 subjects, 72 were members of 35 different families, 15 (7.2%) had increased salivary amylase, and 9 (4.3%) had macroamylasemia. Wide day-to-day fluctuations of pancreatic enzymes, including falls within the reference ranges, were recorded. CONCLUSIONS: All enzymes were increased in benign pancreatic hyperenzymemia, with lipase showing the highest elevation. Doctors should reassure patients about the benign nature of this condition and limit repeating useless examinations

Gut microbiota and its pathophysiology in disease paradigms

The gut flora carries out important functions for human health, although most of them are still unknown, and an alteration of any of them, due to a condition of dysbiosis, can lead to relevant pathological implications. Commensal bacteria in the gut are essential for the preservation of the integrity of the mucosal barrier function and an alteration in the anatomic functional integrity of this barrier has been implicated in the pathophysiologic process of different diseases. The gut microflora plays a role in modulating the intestinal immune system; in fact, it is essential for the maturation of gut-associated lymphatic tissue, the secretion of IgA and the production of antimicrobial peptides. The enteric flora represents a potent bioreactor which controls several metabolic functions, even if most of them are still unknown. The main metabolic functions are represented by the fermentation of indigestible food substances into simple sugars, absorbable nutrients, and short-chain fatty acids. Furthermore, the gut microbiota exerts important trophic and developmental functions on the intestinal mucosa. This overview focuses briefly on the physiological role of the gut microbiota in maintaining a healthy state and the potential role played by disturbances of both the function and composition of the gut microbiota in determining important pathological conditions, such as irritable bowel syndrome, inflammatory bowel disease, metabolic syndrome, obesity, and cance

The role of matricellular proteins and tissue stiffness in breast cancer: A systematic review

Malignancies consist not only of cancerous and nonmalignant cells, but also of additional elements, as extracellular matrix. The aim of this review is to summarize meta-analyses, describing breast tissue stiffness and risk of breast carcinoma (BC) assessing the potential relationship between matricellular proteins (MPs) and survival. A systematic computer-based search of published articles, according to PRISMA statement, was conducted through Ovid interface. Mammographic density and tissue stiffness are associated with the risk of BC development, suggesting that MPs may influence BC prognosis. No definitive conclusions are available and additional researches are required to definitively clarify the role of each MP, mammographic density and stiffness in BC development and the mechanisms involved in the onset of this malignancy