Molecular and Circulating Biomarkers of Brain Tumors

Brain tumors are the most common malignant primary intracranial tumors of the central nervous system. They are often recognized too late for successful therapy. Minimally invasive methods are needed to establish a diagnosis or monitor the response to treatment of CNS tumors. Brain tumors release molecular information into the circulation. Liquid biopsies collect and analyze tumor components in body fluids, and there is an increasing interest in the investigation of liquid biopsies as a substitute for tumor tissue. Tumor-derived biomarkers include nucleic acids, proteins, and tumor-derived extracellular vesicles that accumulate in blood or cerebrospinal fluid. In recent years, circulating tumor cells have also been identified in the blood of glioblastoma patients. In this review of the literature, the authors highlight the significance, regulation, and prevalence of molecular biomarkers such as O6-methylguanine-DNA methyltransferase, epidermal growth factor receptor, and isocitrate dehydrogenase. Herein, we critically review the available literature on plasma circulating tumor cells (CTCs), cell-free tumors (ctDNAs), circulating cell-free microRNAs (cfmiRNAs), and circulating extracellular vesicles (EVs) for the diagnosis and monitoring of brain tumor. Currently available markers have significant limitations. While much research has been conductedon these markers, there is still a significant amount that we do not yet understand, which may account for some conflicting reports in the literature

Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) in the cancer diseases. Clinica Chimica Acta 395

Abstract Background: Various alcohol dehydrogenase (ADH) isoenzymes and aldehyde dehydrogenase (ALDH) exist in the pancreas. Moreover, ADH and ALDH are present in pancreatic cancer cells. The activity of ADH class III isoenzymes is significantly higher in cancerous than in healthy tissues. The expression of these enzymes in cancer cells is reflected by increased enzyme activity in the sera and thus could be helpful for diagnosing pancreatic cancer. The aim of this study was to investigate the potential role of ADH and ALDH as tumor markers for pancreatic carcinoma. methods: Serum samples were taken from 165 patients with pancreatic cancer and 166 healthy controls. Total ADH activity and class III and IV isoenzymes were measured by photometric and ALDH activity, ADH I and II by the fluorometric method. Results: There was a significant increase in the activity of ADH III isoenzyme (14.03 mU/l vs 11.45 mU/l; p < 0.001) and total ADH activity in the sera of pancreatic cancer patients compared to the control. The diagnostic sensitivity for ADH III was 70%, specificity 76%, positive and negative predictive values were 79% and 71% respectively. Area under ROC curve for ADH III was 0.64. Conclusion: The results suggest a potential role for ADH III as a marker of pancreatic cancer

Intrahepatic Cholestasis in Pregnancy: Review of the Literature

Intrahepatic cholestasis of pregnancy (ICP) is the most common hepatic disorder related to pregnancy in women. It usually develops within the third trimester of pregnancy and presents with pruritus as well as elevated levels of bile acid and/or alanine aminotransferase. Clinical signs quickly resolve after delivery; however, there is a high risk of the disorder recurring in subsequent pregnancies. ICP is associated with an increased risk of perinatal complications (premature birth, respiratory disorders, even stillbirth). Elevated levels of gestational hormones and genetic predispositions are important factors for the development of ICP; among the latter, mutations in hepatobiliary transport proteins (multidrug resistance protein 3-MDR3, bile salt export pump- BSEP) play a major role. Clinical and biochemical symptoms of ICP include pruritus and increased levels of total bile acids (TBA). Serum levels of TBA should be monitored in ICP patients throughout the pregnancy as concentrations above 40 μmol/L, which define that severe ICP isassociated with an increased risk of fetal complications. Therapeutic management is aimed at reducing the clinical symptoms, normalizing maternal biochemistry and preventing complications to the fetus. Pharmacological treatment of intrahepatic cholestasis of pregnancy consists of the administration of ursodeoxycholic acid to lower the levels of TBA and possibly reduce pruritus. If the treatment fails, premature delivery should be considered

The activity of class I, II, III and IV alcohol dehydrogenase isoenzymes and aldehyde dehydrogenase in the sera of bladder cancer patients

Objectives. Studies on alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) activity in the sera of patients with malignant neoplasms show that cancer cells in many organs may release ADH isoenzymes into the blood. The aim of this study was to investigate the differences in the activity of ADH isoenzymes and ALDH in the sera of patients with bladder cancer (BCa), and with different grades of the disease. Material and Methods. Blood samples were taken from 39 patients with BCa (15 patients with low-grade and 24 with high-grade BCa) and from 60 healthy subjects. Class III and IV of ADH and total ADH activity were measured using the photometric method, while class I and II ADH and ALDH activity using the fluorometric method with class-specific fluorogenic substrates. Results. The activity of the class I ADH isoenzyme and total ADH was significantly higher in the sera of BCa patients as compared to control group. Analysis of ALDH activity did not show statistically significant differences between the tested groups. Significantly higher total activity of ADH in comparison to control was found in both, low-grade and high-grade BCa group. The activity of ADH class I was also significantly higher in high-grade BCa group when compared to low-grade patients and controls. Conclusion. The increase of total ADH activity in the sera of BCa patients seems to be caused by isoenzymes released from cancerous cells. The higher activity of ADH I probably resulted from metastatic tumors as significant increase was detected only in the sera of high-grade bladder cancer patients

Alzheimer’s Disease—Biochemical and Psychological Background for Diagnosis and Treatment

There is a paucity of empirical research on the use of non-pharmacological interventions to both treat and curb the spread of Alzheimer’s disease (AD) across the globe. This paper examines the biochemical and clinical outlook and the social implications of the condition in relation to psychological aspects that may indicate a direction for further interventions. There is a scarcity of research on the effectiveness of using various psychological aspects of AD, a disease characterized by a process of transition from health and independence to a dependent state with a progressive loss of memory and functional skills. The paper investigates the biochemical and psychological aspects of AD and their significance for improving quality of life for patients with this disease. Psychological interventions based on, among other factors, biochemical studies, are conducted to improve the emotional wellbeing of AD patients and may assist in slowing down the progression of the disease. To date, however, no effective methods of AD treatment have been established

The alcohol dehydrogenase isoenzyme (ADH IV) as a candidate tumour marker of esophageal cancer

Objective: Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are present in esophageal cancer cells. Moreover the total activity of ADH as well as the activity of class IV ADH isoenzyme is significantly higher in cancer tissue than in healthy mucosa. The activity of these enzymes in cancer cells is reflected in the sera and could thus be helpful for diagnostics of esophageal cancer. The aim of this study was to investigate a potential significance of ADH isoenzymes and ALDH as tumour markers of esophageal cancer. We defined diagnostic sensitivity, specificity, predictive value for positive and negative results, and receiver-operating characteristics (ROC) curve for tested enzymes. Methods: Serum samples were taken for routine biochemical investigation from 180 patients with esophageal cancer before treatment. Total ADH activity was measured by a photometric method with p-nitrosodimethylaniline as a substrate and ALDH activity by a fluorometric method with 6-methoxy-2-naphtaldehyde as a substrate. For the measurement of the activity of class I and II isoenzymes we employed the fluorometric methods, with class-specific fluorogenic substrates. The activity of class III alcohol dehydrogenase was measured by a photometric method with formaldehyde and class IV with m-nitrobenzaldehyde as a substrate. Results: There was a significant increase in the activity of class IV of ADH isoenzyme (7.65 mU/l vs 5.88 mU/l) and total ADH activity (1198 mU/l vs 848 mU/l) in the sera of esophageal cancer patients compared to the control. The diagnostic sensitivity for ADH IV was 72%, the specificity 76%, the positive and negative predictive values were 80% and 72% respectively. The area under the ROC curve for ADH IV was 0.65. Conclusion: The results suggest a potential significance of ADH IV as a marker of esophageal cancer

The diagnostic value of alcohol dehydrogenase (ADH) isoenzymes and aldehyde dehydrogenase (ALDH) measurement in the sera of patients with brain tumor

Introduction: Alcohol dehydrogenase (ADH) isoenzymes and aldehyde dehydrogenase (ALDH) exist in the brain. Alcohol dehydrogenase and ALDH are also present in brain tumor cells. Moreover, the activity of class I isoenzymes was significantly higher in cancer than healthy brain cells. The activity of these enzymes in tumor tissue is reflected in the serum and could thus be helpful for diagnostics of brain neoplasms. The aim of this study was to investigate the potential role of ADH and ALDH as markers for brain tumors. Material and methods: Serum samples were taken for routine biochemical investigation from 115 patients suffering from brain tumors (65 glioblastomas, 50 meningiomas). For the measurement of the activity of class I and II ADH isoenzymes and ALDH activity, fluorometric methods were used. The total ADH activity and activity of class III and IV isoenzymes were measured by the photometric method. Results : There was a significant increase in the activity of ADH I isoenzyme and ADH total in the sera of brain tumor patients compared to the controls. The diagnostic sensitivity for ADH I was 78%, specificity 85%, and positive and negative predictive values were 86% and 76% respectively. The sensitivity and specificity of ADH I increased with the stage of the carcinoma. Area under receiver-operating characteristic curve for ADH I was 0.71. Conclusions : The results suggest a potential role for ADH I as a marker for brain tumor

Activity of Total Alcohol Dehydrogenase, Alcohol Dehydrogenase Isoenzymes and Aldehyde Dehydrogenase in the Serum of Patients with Alcoholic Fatty Liver Disease

Background and objectives: The aim of the current study was to assess the use of determinations of total alcohol dehydrogenase and the activity of its isoenzymes as well as aldehyde dehydrogenase in the serum of patients with alcohol liver disease. Materials and Methods: The testing was performed on the serum of 38 patients with alcoholic fatty liver (26 males and 12 females aged 31–75). The total activity of ADH was determined by the colorimetric method. The activity of ADH I and ADH II, as well as ALDH, was determined by the spectrofluorometric method using fluorogenic specific substrates. The activity of isoenzymes of other classes was determined by spectrophotometric methods using substrates. Results: A statistically significantly higher ADH I activity was noted in the serum of patients with alcoholic fatty liver (4.45 mIU/L) compared to the control group (2.04 mIU/L). A statistically significant increase in the activity was also noted for the class II alcohol dehydrogenase isoenzyme (29.21 mIU/L, control group: 15.56 mIU/L) and the total ADH (1.41 IU/L, control group: 0.63 IU/L). Conclusions: The obtained results imply the diagnostic usefulness of the determination of AHD total, ADH I, and ADH II activity in the serum of patients with alcoholic fatty liver