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Title: The effect of gastrin and non-amidated gastrin peptides on interactions between receptors activated by peroxisome proliferators (PPARy) and mechanisms of intestinal carcinogenesis and apoptosis in in vitro cancer models
Abstract:
Gastrointestinal cancer by The World Health Organization poses a serious threat to public health. The latest data from the National Cancer Registry from 2015 show that over 30,000 Poles have fallen ill with this type of cancer, including as many as 18,500 with colorectal cancer. The main reason for the increase in the incidence of gastrointestinal cancers is the progressive aging of the population. This disease mainly affects older people. However, it may be disturbing that gastrointestinal cancers, especially colorectal cancer, are also beginning to affect young people. According to the American Cancer Society, in 1995-2013, the incidence of this type of cancer in people aged under 50 increased by 22% in the USA. Other predisposing factors, such as diet, limited physical activity, environmental pollution and smoking are also important. There are also reports on the important role of intestinal microbiome in the development of gastrointestinal cancers. Other gastrointestinal cancers are less common than colorectal cancer, but they have a significantly higher mortality rate. This is the case with pancreatic cancer. Currently, in the case of such neoplastic lesions, only surgical intervention at a specific stage of the disease is a treatment that can provide a chance of survival. Unfortunately, among the group of patients who have extensive metastases or advanced cancer progressi ; on, complete surgical resection is not always possible, and the available forms of non-surgical therapy also prove to be inefficient. In the fight against cancer, getting to know the mechanisms associated with the process of apoptosis gives high hopes. It is believed that a measure of the effectiveness of cancer therapy is inhibition of the proliferation process and, above all, the ability to induce apoptosis in cancer cells. Therefore, a better understanding of molecular mechanisms and signaling pathways affecting apoptosis can lead to the creation of a rational anti-cancer strategy that will contribute to the successful treatment of cancer patients in the future. The aim of the research being the subject of the doctora! dissertation was to determine the effect of gastrin and non-amidated gastrin peptides on interactions between PPARy nuclear receptors and the WNT!p-catenin cell signaling pathway in in vitro gastrointestinal cancer models. Studies were conducted in vitro on selected cell lines (PANC-1, OE-33) originating from gastrointestinal cancer. The trophic effect of gastrin and gastrin precursors on selected cell lines was investigated using an MTT test. Experiments were also conducted to assess the effect of gastrin and gastrin precursors on interactions between PP ARy nuclear receptors and the WNT/P-catenin cell signaling pathway. Immunoblotting techniques were used f ; or analyzes carried out at the protein level. It has been observed that gastrin and Gly-gastrin at a specific concentration of 1o·6 and 1o·5 [M] have trophic effects, and have an effect on the P-catenin protein and the activity of PP ARy receptors. The increase in P-catenin expression may affect the PPARy nuclear receptor activity, however, this effect was only noticeable in the PANC-1 cell line. In tum, in the OE-33 cell line, induction of B-catenin protein was observed to weaken PP Ary receptor activity. The obtained results confirm the thesis that in some gastrointestinal neoplasms we observe a decrease in PP ARy activity with a simultaneous increase in the activity of the WNT-P-catenin pathway due to the action of gastrin precursors. An increase in the activity of the WNT-P-catenin pathway is conducive to inhibiting the process of apoptosis by increasing the expression of P-catenin protein in the studied tumor cell lines.
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Degree discipline:
onkologia ; choroby układu trawiennego ; biochemia
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Rada Dyscypliny Nauki medyczne
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Last modified:
Apr 8, 2024
In our library since:
Jan 26, 2022
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http://dl.cm-uj.krakow.pl:8080/publication/4460
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| Edition name | Date |
|---|---|
| ZB-132971 | Apr 8, 2024 |
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