Tissue inhibitors of metalloproteinases (TIMPs) suppress matrix metalloproteinase (MMP) activity critical for extracellular matrix turnover associated with both physiologic and pathologic tissue remodeling. We demonstrate here that TIMP-2 abrogates angiogenic factor-induced endothelial cell proliferation in vitro and angiogenesis in vivo independent of MMP inhibition. These effects require alpha 3 beta 1 integrin-mediated binding of TIMP-2 to endothelial cells. Further, TIMP-2 induces a decrease in total protein tyrosine phosphatase (PTP) activity associated with beta1 integrin subunits as well as dissociation of the phosphatase SHP-1 from beta1. TIMP-2 treatment also results in a concomitant increase in PTP activity associated with tyrosine kinase receptors FGFR-1 and KDR. Our findings establish an unexpected, MMP-independent mechanism for TIMP-2 inhibition of endothelial cell proliferation in vitro and reveal an important component of the antiangiogenic effect of TIMP2 in vivo.
Coronavirus-19 (COVID-19) caused by SARS-CoV-2 has become a global pandemic. Risk of transmission may occur during endoscopy and the goal is to prevent infection among healthcare professionals while providing essential services to patients. Asia was the first continent to have a COVID-19 outbreak, and this position statement of the Asian Pacific Society for Digestive Endoscopy shares our successful experience in maintaining safe and high-quality endoscopy practice at a time when resources are limited. Sixteen experts from key societies of digestive endoscopy in Asia were invited to develop position statements, including patient triage and risk assessment before endoscopy, resource prioritisation and allocation, regular monitoring of personal protective equipment, infection control measures, protective device training and implementation of a strategy for stepwise resumption of endoscopy services after control of the COVID-19 outbreak.
In recent years a peculiar type of chronic pancreatitis with underlying autoimmunity has been described. Lymphoplasmacytic infiltration and fibrosis on histology and elevated IgG levels or detected autoantibodies on laboratory data support the concept of autoimmune chronic pancreatitis (AIP). Pancreatic imaging reveals a rare association of diffuse enlargement of the pancreas and irregular narrowing of the main pancreatic duct, which is unique and specific to AIP. Although AIP is not a common disease, it is increasingly being recognized as knowledge of this entity builds up. Clinically it is very important to be aware of this disease because AIP can clinically disguise as pancreaticobiliary malignancies, ordinary chronic, or acute pancreatitis. Above all, AIP is a very attractive disease to clinicians in terms of its dramatic response to oral steroid therapy in contrast to ordinary chronic pancreatitis. This review discusses the clinical, laboratory, histologic, and imaging findings that are seen in patients with AIP, especially focusing on the diagnosis.
Hilar cholangiocarcinoma (HCCA) is one of the most common types of hepatobiliary cancers reported in the world including Asia-Pacific region. Early HCCA may be completely asymptomatic. When significant hilar obstruction develops, the patient presents with jaundice, pale stools, dark urine, pruritus, abdominal pain, and sometimes fever. Because no single test can establish the definite diagnosis then, a combination of many investigations such as tumor markers, tissue acquisition, computed tomography scan, magnetic resonance imaging/magnetic resonance cholangiopancreatography, endoscopic ultrasonography/intraductal ultrasonography, and advanced cholangioscopy is required. Surgery is the only curative treatment. Unfortunately, the majority of HCCA has a poor prognosis due to their advanced stage on presentation. Although there is no survival advantage, inoperable HCCA managed by palliative drainage may benefit from symptomatic improvement. Currently, there are three techniques of biliary drainage which include endoscopic, percutaneous, and surgical approaches. For nonsurgical approaches, stent is the most preferred device and there are two types of stents i.e. plastic and metal. Type of Declarations of conflict of interest: All authors have nothing to disclose.Author contributions: RR was involved with the consensus concept and design, acquisition of data, drafting of the manuscript, critical revision of the manuscript, obtain funding, and participation in electronic and face-to-face voting. PA and TR were involved with the consensus concept and design, acquisition of data, drafting of the manuscript, critical revision of the manuscript, and participation in electronic and face-to-face voting. CK, RP, JM, DS, LP, AS, PP, TA, DR, AM, SP, PK, MR, and MK were involved with drafting of the manuscript, critical revision of the manuscript, and participation in electronic and face-to-face voting. TI was involved with drafting of the manuscript, critical revision of the manuscript, and participation in electronic voting. NP, ST, SA, BD, HW, EO, DL, and PM were involved with critical revision of the manuscript, and participation in electronic and face-to-face voting. KG and BO were involved with critical revision of the manuscript and participation in electronic voting. SC and AJ were involved with study supervision and participation in electronic voting. VB was involved with study supervision. and number of stent for HCCA biliary drainage are subjected to debate because the decision is made under many grounds i.e. volume of liver drainage, life expectancy, expertise of the facility, etc. Recently, radio-frequency ablation and photodynamic therapy are promising techniques that may extend drainage patency. Through a review in the literature and regional data, the Asia-Pacific Working Group for hepatobiliary cancers has developed statements to assist clinicians in diagnosing and managing of HCCA. After voting anonymously using modified Delphi method, all final statements were determined for the level of evidence qual...
Autoimmune chronic pancreatitis (AIP) is increasingly being recognized worldwidely, as knowledge of this entity builds up. Above all, AIP is a very attractive disease to clinicians in terms of its dramatic response to the oral steroid therapy in contrast to ordinary chronic pancreatitis. Although many characteristic findings of AIP have been described, definite diagnostic criteria have not been fully established. In the year 2002, the Japan Pancreas Society published the diagnostic criteria of AIP and many clinicians around the world use these criteria for the diagnosis of AIP. The diagnostic criteria proposed by the Japan Pancreas Society, however, are not completely satisfactory and some groups use their own criteria in reporting AIP. This review discusses several potential limitations of current diagnostic criteria for this increasingly recognized condition. The manuscript is organized to emphasize the need for convening a consensus to develop improved diagnostic criteria.
Our results indicate that development of ICC seems to be more closely related to HBV infection than to HCV infection in Korea, where both HBV and ICC are endemic.
The current guidelines on interventional EUS procedures are the first published by an endoscopic society. These guidelines provide an in-depth review of the current evidence and standardise the management of the procedures.
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