Microsatellite instability (MSI) is a marker of the replication error phenotype. It is caused by impaired DNA mismatch repair processes (MMR), resulting in ineffectiveness of the mechanisms responsible for the DNA replication precision and postreplicative DNA repair. MSI underlies the pathogenesis of 10%–20% of colorectal cancer (CRC) cases. The data about the potential value of MMR status as a predictive factor for 5-fluorouracil (FU)-based chemotherapy remain unclear. According to National Comprehensive Cancer Network updated guidelines, MSI testing is recommended for all patients with stage II CRC because patients with MSI-H (high-frequency MSI) tumour may have a good prognosis and obtain no benefit from 5-FU-based adjuvant chemotherapy. The significance of the MSI status as a predictive factor for patients with metastatic disease was not confirmed. The association between the MSI status and the efficacy of the therapy based on anti-programmed death-1 receptor inhibitors requires further studies.
Some molds commonly occurring in the natural environment produce mycotoxins in the process of secondary metabolism. Aspergillus flavus and A. parasiticus are species of molds, which are responsible for the production of aflatoxins and are crucial in the pathogenesis of human diseases. Aspergillus species present in decaying plants, the soil and their spores are transferred via air currents and insects to crops and food storages. Aflatoxins B1, B2, G1, G2, M1 and M2 are the most common derivatives of aflatoxins. Ingestion of contaminated food is the main source of exposure to aflatoxins, which adversely affect the health of both humans and animals. The compounds can cause acute or chronic toxic effects of a teratogenic, mutagenic, carcinogenic, immunotoxic or hepatotoxic character. Molecular aflatoxins affect DNA mutations, postranslation peptids chains modification, proteins and nucleic acids methylation and the formation of free radicals.Due to aflatoxins carcinogenic features and frequent occurrence in food and forages they are routinely examinated in some groceries and agricultural products.
Malondialdehyde (MDA) found in the body comes from two sources: food consumed and lipid peroxidation occurring in the tissues. The formation of MDA and the scale and rate of lipid oxidation in the tissues of living organisms is influenced by a number of endo-and exogeneous factors. The products of lipid peroxidation, in particular MDA, exhibit cytotoxic, mutagenic and carcinogenic properties. They can also inhibit enzymes associated with defending cells against oxidative stress. Not only do the occurring processes contribute to the development of many diseases, but they are also a part of the aging process. The body defends itself to some extent against the effects of free radicals by trapping and neutralising them. The main source of antioxidants is food products of plant origin. Lifestyle, the components of which are diet and physical activity, is an important element in preserving health understood as physical and psychological well-being. Dietary habits and a diet rich in antioxidants are modifiable factors which not only prevent age-associated diseases, but also delay aging processes. K E Y W O R D S lifestyle, free radicals, aging ST R ES ZCZ E NI E Dialdehyd malonowy (MDA) w organizmie człowieka pochodzi z dwóch źródeł: spożywanego pokarmu i peroksyda-cji lipidów występujących w tkankach. Powstawanie MDA, a także wielkość i szybkość utleniania lipidów w tkankach organizmów żywych, zależy od wielu czynników endo-i egzogennych. Produkty peroksydacji lipidów, szczególnie
Introduction. The ability to form metastases which depends on the mechanisms of cell migration is an important element of the progression of cancer. In the present study we analyzed the genes involved in the regulation of migration in colon cancer cells. Materials and Methods. A total of 20 pairs of surgically removed tumoral and healthy (marginal) tissues samples from colorectal cancer patients at clinical stages I-II and III-IV were analyzed. The isolation of RNA from CRC and normal tissues and its subsequent molecular analysis were performed according to manufacturer's instructions. Microarray data analysis was performed using the GeneSpring 11.5 platform and Significance Analysis of Microarrays (SAM). In SAM analysis to identify significantly differentially expressed genes score and q-value parameters were used. Results. The largest increase in expression of genes was shown by MMP9, ADAM17, EphA2, and TIMP. Conclusions. Presented genes, especially ADAM17, MMP9, EphA2, TIMP1, ICAM 11, and CD4, may be used as prognostic markers of advanced stages of colorectal cancer, contributing to the development of new lines of therapy focused on reducing metastasis of the primary tumor.
Colorectal cancer (CRC) is the third most common malignant neoplasm worldwide. In Poland, colorectal cancer ranks second in tumor incidence regardless of sex; moreover, there has been a steady increase in the incidence of CRC. CRC results from complex interactions between inherited susceptibility, clinical conditions and environmental/lifestyle-related risk factors such as physical inactivity, smoking, alcohol consumption, high-fat/low-fiber diet, and obesity/overweight. The activation of pathways associated with insulin resistance and insulin-like growth factors (IGF) appears to be the epidemiological link between the metabolic syndrome and the development of CRC, which is of particular importance. What is significantly associated with the pathway of IGF is ADAM12 and 28-protein, which belong to a broad family of the adamalysines. These proteins, by adjusting the bioavailability of growth factors, influence the process of carcinogenesis. The aim of this article is to analyze the role of selected adamalysines and activation of the IGF system associated with the formation of colon cancer.
Colorectal cancer is one of the most common cancers in the world. Due to its still undetermined pathogenesis, we are searching for signaling pathways that are important in the development of colorectal cancer. In this article, we present results of study on the role of ADAM proteins in colorectal cancer. The study included 85 adult colorectal cancer patients (48 men, 37 women) and 25 patients in the control group (after diagnostic colonoscopy—without cancer). During hospitalization, a serum sample (3 cm3) was collected from the study and control group, anthropometric measurements were conducted and others clinical data were analyzed. In the serum ADAM10, 12, 17, and 28, protein concentrations were determined and, in the next step, examined the relationship between ADAMs concentrations and selected clinical parameters in both groups. The analysis showed that serum levels of ADAM10 and ADAM28 are significantly higher in patients with colorectal cancer and correlate with histopathological grading and with presence of distant metastases. Moreover, noticed the trend to correlate concentrations of adamalysines with higher BMI score. One of the functions of adamalysines is the activation of growth factors involved in cancer, including IGF and TNFα. The increased activity of adamalysines in patients may play a role in the pathogenesis of colorectal cancer. Our study highlights the prevalence of metabolic disorders in the group of patients with diagnosed CRC, and this cancer seems to be a further complication of obesity.
Toll-like receptors (TLRs) are involved in transduction of molecular signals in immune process such as induction and regulation of immunity, production of cytokines, and recognition of specific molecular patterns on the surface of microorganisms, but also in cancer development—which was partially proven in previous studies. There is a lack of detailed research on differentiating levels of TLR expression in colorectal cancer at different stages of its advancement, so in our study we want to determine whether there is such a difference of TLRs and TLR-connected protein expression. In this study, 83 samples of colorectal adenocarcinoma (varying clinical degrees) and 40 slices of healthy colon tissue have been analyzed. The delivered material was subjected to homogenization and extraction of total RNA. The isolated RNA was subsequently purified and valued quantitatively and qualitatively. Quantification was performed using a spectrophotometer GeneQuant II. The RNA concentration in the tested samples was determined spectrophotometrically. A qualitative assessment was performed by performing electrophoresis on a 1% agarose gel stained with ethidium bromide. The expression profile of the genes encoding the TLRs was determined using oligonucleotide microarray HG-U133A. To determine the mRNA (messenger RNA), differentiate cancerous tissue from normal colon using PL-Grid Infrastructure. The results were analyzed statistically, taking a significance level P < 0.05. In the study were found three proteins, DUSP2, IFNγ, EIF4A1, associated with TLR system, that differentiate early stages of colorectal cancer of healthy tissue, moreover eleven, inter alia: vascular endothelial growth factor (VEGF), which differentiate high stage of cancer of healthy tissues. The results emphasize the role of pathways associated with TLR activation in the pathogenesis of colorectal cancer. In summary, molecular studies on the development of colorectal cancer will enable the introduction of minimally invasive genetic diagnosis of early forms of cancer. In addition, identification of new signaling pathways can provide the basis for developing new therapeutic methods.
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