Search results for "digestive system"

In the literature: April 2020

2020

Deficient DNA mismatch repair (dMMR) may be caused by germline or somatic mutations in mismatch repair genes ( MLH1 , MSH2 , MSH3 , MSH6 and PMS2 ) or through epigenetic silencing of MLH1 .1 dMMR induces a hypermutator phenotype, also known as microsatellite instability (MSI). Next-generation sequencing identifies MSI in 12 cancer types. The highest prevalence is seen in endometrial cancer (31.4%), followed by colorectal cancer (19.7%) and gastric cancer (GC, 19.1%). MSI was related to better prognosis for colorectal cancer and GC . Moreover, the dMMR/MSI hypermutator phenotype is thought to produce large numbers of immunogenic neoantigens that can be recognised by immune cells, leading to …

Phosphorylation of mismatch repair proteins MSH2 and MSH6 affecting MutSα mismatch-binding activity

2002

Mismatch repair (MMR) is involved in the removal of mispaired bases from DNA and thus plays an important role in the maintenance of genomic stability and the prevention of mutations and cancer. Moreover, MMR triggers genotoxicity and apoptosis upon processing of DNA lesions such as O6-methylguanine. Whereas the enzymology of MMR has been elucidated in great detail, only limited data are available concerning its regulation. Here we show that the major mismatch-binding proteins MSH2 and MSH6, forming the MutSalpha complex, are phosphorylated in vitro by protein kinase C and casein kinase II, but not by protein kinase A. Phosphorylation of MSH2 and MSH6 was also found within the cell, with MSH…

Cytotoxicity investigations of plasma sprayed calcium phosphate coatings

1994

One potential alternative material to replace hydroxyapatite (HAp) as a coating material for plasma-sprayed coatings on implants for hip replacement is fluorapatite (FAp). FAp has advantages over HAp regarding the capability of being chemically stable during the coating process. This leads to surface coatings containing high apatite rates with a mechanical stability (bond strength, microhardness) comparable to HAp. From the technical point of view the production of FAp coatings is well investigated, although studies on biocompatibility of FAp coatings are fewer. This paper reports the production of HAp and FAp coatings with varying solubilities by plasma spraying and their in vitro cytotoxi…

Expression of hMLH1 and hMSH2 proteins in ameloblastomas and tooth germs

2017

Background Mismatch repair proteins (MMRPs) are a group of nuclear enzymes that participate in the repair of base mismatches that occur during DNA replication in all proliferating cells. The most studied MMRPs are hMSH2 and hMLH1, which are known to be highly expressed in normal tissues. A loss of MMRPs leads to the accumulation of DNA replication errors in proliferating cells. Ki-67 is a biomarker regarded to be the gold-standard tool for determining cell proliferation by immunohistochemical methods. The aim of this study was to investigate the immunohistochemical expression of hMLH1, hMSH2 and Ki-67 proteins in ameloblastomas and tooth germs, to contribute to the understanding of the deve…

Follow-up in transthyretin familial amyloid polyneuropathy: Useful investigations

2020

Patients with transthyretin amyloid polyneuropathy (TTR-FAP) and asymptomatic mutation-carriers have to be regularly followed-up in order to identify disease progression and the time point for starting or modifying therapy. In this case series we describe the potential suitability of different variables as progression markers. We retrospectively analyzed the follow-up charts of 10 TTR-FAP patients. Clinical examination included the Neuropathy Impairment Score of Lower Limb (NIS-LL), temperature perception thresholds, nerve conduction and autonomic function tests. The NIS-LL had the greatest value for a sensitive and correct follow-up for all TTR-FAP stages. All other examinations provided u…

Genetische Hämochromatose und das HFE-Gen: von der Molekulargenetik zur klinischen Diagnostik

2000

More than 90% of patients with genetic hemochromatosis carry a characteristic mutation in the HFE-gene (C282Y). HFE modulates the iron uptake by the transferrin receptor. Duodenal crypt cells of HFE-knockout mice show low intracellular iron concentrations which lead to an upregulation of the divalent metal transporter and enhanced iron uptake by duodenal enterocytes. Heterozygosity for the C282Y mutation appears to alter the course of other liver diseases like porphyria cutanea tarda and nonalcoholic steatohepatitis.

The case for simplifying and using absolute targets for viral hepatitis elimination goals

2021

The 69th World Health Assembly endorsed the Global Health Sector Strategy for Viral Hepatitis, embracing a goal to eliminate hepatitis infection as a public health threat by 2030. This was followed by the World Health Organization's (WHO) global targets for the care and management of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. These announcements and targets were important in raising awareness and calling for action; however, tracking countries’ progress towards these elimination goals has provided insights to the limitations of these targets. The existing targets compare a country's progress relative to its 2015 values, penalizing countries who started their programmes …

Endoscopic ultrasound-guided choledochoduodenostomy: a propos of two cases

2014

Cannabidiol treatment might promote resilience to cocaine and methamphetamine use disorders: A review of possible mechanisms

2019

Currently, there are no approved pharmacotherapies for addiction to cocaine and other psychostimulant drugs. Several studies have proposed that cannabidiol (CBD) could be a promising treatment for substance use disorders. In the present work, the authors describe the scarce preclinical and human research about the actions of CBD on the effects of stimulant drugs, mainly cocaine and methamphetamine (METH). Additionally, the possible mechanisms underlying the therapeutic potential of CBD on stimulant use disorders are reviewed. CBD has reversed toxicity and seizures induced by cocaine, behavioural sensitization induced by amphetamines, motivation to self-administer cocaine and METH, context- …

Supplementary Material for: Cabozantinib in Advanced Hepatocellular Carcinoma: Efficacy and Safety Data from an International Multicenter Real-Life C…

2021

Background and Aims: The multikinase inhibitor cabozantinib has been approved for hepatocellular carcinoma (HCC) previously treated with sorafenib. We report safety and efficacy data of an international, multicenter, real-life cohort of patients with advanced HCC treated with cabozantinib. Methods: Patients with HCC who were treated with cabozantinib were retrospectively identified across 11 centers in Austria, Switzerland, and Germany. Patients’ characteristics, adverse events, duration of treatment and overall survival (OS) data were analyzed until April 1, 2020. Results: Eighty-eight patients from 11 centers were included. The predominant underlying liver diseases were NAFLD/NASH in 26 (…