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Immunotherapy and checkpoint inhibitors for gliomas

Neuroimmunology and Neuroinflammation 2018年第11期5卷 19-34页

作者： Clairice M.Pearce matthew r.chrostek Emily G.Fellows Nikolas G.Toman Sarah K.Tran Andrew T.Crane Walter C.Low Department of Neurosurgery University of Minnesota Medical SchoolMinneapolisMN 55455USA Masonic Cancer Center University of Minnesota Medical SchoolMinneapolisMN 55455USA Brain Tumor Program University of Minnesota Medical SchoolMinneapolisMN 55455USA

Glioma treatments are faced with challenges, including the inability to fully eliminate cancer stem cells, the immunosuppressive tumor microenvironment, and the blood brain barrier. Although progress has been made with surgical, radiation, and chemotherapies, prognosis for patients remains poor. rapidly emerging immunotherapies may be able to address the challenges that conventional techniques cannot. Immunotherapies manipulate the patient's immune system to selectively combat malignancies. Therapies often work to enhance T-cell and natural killer (NK) cell function, which can both eliminate tumor cells and enhance remission. Vaccines encourage in vivo development of anti-tumor T-cells and NK cells, while adoptive transfer techniques focus on engineering immune cells ex vivo before reintroducing them to patients. Vaccine and adoptive transfer therapies have been shown to induce enhanced immune responses in patients but have not always correlated with improved outcomes, likely because of the tumor immunosuppressive microenvironment. Checkpoint inhibitors can impair these tumor immunosuppressive capabilities. Although no one treatment has been able to consistently eliminate gliomas and maintain remission, combinations of vaccines or adoptive transfer techniques in conjunction with immune checkpoint inhibitors offers promise.

关键词： Glioma immunotherapy checkpoint inhibitors vaccines T-cells dendritic cells

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Liver fibrosis markers in alcoholic liver disease

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World Journal of Gastroenterology 2014年第25期20卷 8018-8023页

作者： Lech chrostek Anatol Panasiuk Department of Biochemical Diagnostics Medical University of Bialystok 15-540 Bialystok Poland Department of Infectious Diseases and Hepatology Medical University of Bialystok 15-540 BialystokPoland

Alcohol is one of the main factors of liver damage. The evaluation of the degree of liver fibrosis is of great value for therapeutic decision making in patients with alcoholic liver disease(ALD). Staging of liver fibrosis is essential to define prognosis and management of the disease. Liver biopsy is a gold standard as it has high sensitivity and specificity in fibrosis diagnostics. Taking into account the limitations of liver biopsy, there is an exigency to introduce non-invasive serum markers for fibrosis that would be able to replace liver biopsy. Ideal serum markers should be specific for the liver, easy to perform and independent to inflammation and fibrosis in other organs. Serum markers of hepatic fibrosis are divided into direct and indirect. Indirect markers reflect alterations in hepatic function, direct markers reflect extracellular matrix turnover. These markers should correlate with dynamic changes in fibrogenesis and fibrosis resolution. The assessment of the degree of liver fibrosis in alcoholic liver disease has diagnostic and prognostic implications, therefore noninvasive assessment of fibrosis remains important. There are only a few studies evaluating the diagnostic and prognostic values of noninvasive biomarkers of fibrosis in patients with ALD. Several noninvasive laboratory tests have beenused to assess liver fibrosis in patients with alcoholic liver disease, including the hyaluronic acid, FibroTest, FibrometerA, Hepascore, Forns and APrI indexes, FIB4, an algorithm combining Prothrombin index(PI), α-2 macroglobulin and hyaluronic acid. Among these tests, Fibrotest, FibrometerA and Hepascore demonstrated excellent diagnostic accuracy in identifying advanced fibrosis and cirrhosis, and additionally, Fibrotest was independently associated with survival. Therefore, the use of biomarkers may reduce the need for liver biopsy and permit an earlier treatment of alcoholic patients.

关键词： Liver fibrosis markers Alcoholic liver disease

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Liver function in COVID-19 infection

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World Journal of Hepatology 2021年第12期13卷 1909-1918页

作者： Dagmara Przekop Ewa Gruszewska Lech chrostek Diagnostics-Experimental Center of Sexually Transmissible Diseases Bialystok 15-879Poland Department of Biochemical Diagnostics Medical University of BialystokBialystok 15-269Poland

Coronavirus disease 2019(COVID-19)disease affects multiple organs,including anomalies in liver *** this review we summarize the knowledge about liver injury found during severe acute respiratory syndrome coronavirus 2(SArSCoV-2)infection with special attention paid to possible mechanisms of liver damage and abnormalities in liver function tests allowing for the evaluation of the severity of liver *** in liver function observed in COVID-19 disease are associated with the age and sex of patients,severity of liver injury,presence of comorbidity and *** method of antiviral treatment can also impact on liver function,which manifests as increasing values in liver function ***,analysis of variations in liver function tests is necessary in evaluating the progression of liver injury to severe disease.

关键词： COVID-19 Pathogenesis of liver injury Angiotensin-converting enzyme 2 receptor Liver function tests Severe COVID-19 Treatment effect

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结肠直肠癌中Ⅰ、Ⅱ、Ⅲ、Ⅳ型乙醇脱氢酶同工酶和乙醛脱氢酶的活性

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世界核心医学期刊文摘（胃肠病学分册） 2005年第1期1卷 15-16页

作者： Jelski W. Zalewski B. chrostek L. Szmitkowski M. 杨瑗

Chronic ethanol consumption is associated with an increased risk for cancer of the colorectum. The highly toxic and carcinogenic compound is acetaldehyde, the product of ethanol metabolism. Ethanol is metabolized to acetaldehyde by alcohol dehydrogenase (ADH) in colorectal mucosa and bacteria. The enzyme responsible for oxidation of acetaldehyde is aldehyde dehydrogenase. The aim of this study was to compare ADH isoenzymes and ALDH activity in colorectal cancer with the activity in normal colonic mucosa. Total ADH activity was measured by a photometric method with p-nitrosodimethylaniline(NDMA)as substrate, and ALDH activity by a fluorometric method with 6-methoxy-2-naphthaldehyde as a substrate. For measurement of the activity of class I and II isoenzymes we employed fluorometric methods,with class-specific fluorogenic substrates. The activity of class III ADH was measured by the photometric method with n-octanol as substrate, and class IV with m-nitrobenzaldehyde as substrate. Samples were taken surgically during routine operations of colorectal carcinomas from 32 patients. The activities of total ADH and, the most important in colon mucosa, class I ADH were significantly higher in cancer than in healthy tissues. The other tested classes of ADH had a tendency to higher-level activity in cancer cells than in healthy mucosa. ALDH activity was not significantly lower in the cancer cells. The activities of all tested enzymes and isoenzymes were not significantly higher in drinkers than in nondrinkers both in colorectal cancer and in normal *** differences in activities of total ADH and class I isoenzyme between cancer tissues and normal colon mucosa might be a factor for metabolic changes and disturbances in low-mature cancer cells and, additionally, might be a reason for the higher level of acetaldehyde, which can intensify carcinogenesis.

关键词：结肠直肠癌乙醛脱氢酶二甲基苯低分化癌细胞正常结肠黏膜正常黏膜同工酶荧光测定法光度测定法切除物

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