Acquired drug resistance of tumor cells is frequently observed in cancer patients undergoing chemotherapy. We studied murine leukemia L1210 cells sensitive and resistant to the cytotoxic action of cisplatin and showed that cisplatin-resistant leukemia cells were also refractory to TGF /β1-dependent growth inhibition and apoptosis. Addressing the question about the mechanisms responsible for the cross-resistance to cisplatin and TGF /β1, we found that cisplatin- and TGF /β1-resistant L1210 cells possessed a decreased expression of type I TGF /β1 receptor, while the expression of type II TGFβ1 receptor was not affected. Western blot analysis of Smad proteins 2, 3, 4, 6, and 7, which participate in signal transduction pathway down-stream of the TGF /β1 receptors, revealed an increased expression of Smad 6, inhibiting TGF β1 action, only in cisplatin- and TGFβ1-resistant L1210 cells. TGFβ1 and especially the cytotoxic mistletoe agglutinin increased Smad 6 expression in TGF β1-sensitive but not in TGF /β1-resistant L1210 cells. TGF /β1-resistant L1210 cells also differed from TGF /β1-sensitive cells by the lack of expression of the pro-apoptotic p53 protein and higher level of expression of the anti-apoptotic Bcl-2 protein. Thus, the described co-expression of tumor cell refractoriness to an anti-cancer drug and to the inhibitory cytokine TGF β1 is accompanied by multiple changes in the TGF β1 signal transduction pathway and in other regulatory systems of the target cells. Besides, we found that various anti-tumor drugs and cytotoxic plant lectins increased the level of TGF β1 expression in both TGF β1-sensitive and -resistant L1210 cells. A hypothesis is proposed that TGF β1 can at least partly mediate the effect of cell-stressing agents and, thus, the development of TGF β1 resistance may be responsible for the appearance of tumor cell refractoriness to the action of some anti-cancer drugs.
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We have shown that the sera of lung cancer patients affect the response of ConA-stimulated normal peripheral blood mononuclear cells by decreasing the expression of IL-2Rα and inhibiting the release of IL-1β and IL-2. A tendency to enhance the release of IL-6 was also observed. We conclude that an imbalance in the Th1/Th2 cytokine response, typical for cancer patients, may at least partly be related to soluble factors circulating in the patients’ blood. We discuss a putative role of serum IL-10, IL-1ra, and soluble IL-2Rα in the effects observed.
Background. Dietary patterns (DPs) are defined as the amounts, types and combinations of various food products in habitual diets and the frequency of their consumption. Dietary pattern analysis is usually performed in order to assess the combined effect of consumed food products on health. Objective. The aim of the study was to assess and compare the nutritional value of dietary patterns identified in a group of patients staying on the oncological ward. Material and methods. The study group consisted of 100 patients (51 women and 49 men) aged 19-83 years. Dietary intake was assessed using a food frequency questionnaire (FFQ) validated for the population of Lower Silesian Voivodeship. Results. Factor analysis identified two main dietary patterns explaining 25.6% of variance. The “fruit and vegetables” DP consisted of vegetables, fruits, juices, unrefined grains and nuts, seeds and raisins. Instead, the “Western” DP was characterized by the consumption of high-fat and processed meat and poultry, fried fish, refined grains, honey and sugar, fats, sweets, beverages and chips. While higher scores for “fruit and vegetables” pattern were associated with increased intake of dietary fiber, antioxidant vitamins, folic acid and decreased glycemic load per 1000 kcal and sodium intake, for “Western” pattern observed relationships were opposite. Women were more likely to have higher factor scores for “fruit and vegetables” DP and lower factor scores for “Western” DP than men. Conclusions. Dietary patterns identified in the study group differed in terms of nutritional value, in spite of similar macronutrient content in the diet. “Western” DP was characterized by lower nutritional value than “fruit and vegetables” dietary pattern.
A population study is reported in which the DNA damage induced by y-radiation (2 Gy) and the kinetics of the subsequent repair were estimated by the comet and micronucleus assays in isolated lymphocytes of 82 healthy donors and patients with head and neck cancer before radiotherapy. The parameters of background and radiation-induced DNA damage, rate of repair, and residual non-repaired damage were measured by comet assay, and the repair kinetics for every donor were computer-fitted to an exponential curve. The level of background DNA damage before irradiation measured by comet assay as well as the level of micronuclei were significantly higher in the head and neck cancer patient group than in the healthy donors, while the parameters of repair were widely scattered in both groups. Cancer patient group contained significantly more individuals, whose irradiated lymphocytes showed high DNA damage, low repair rate and high non-repaired DNA damage level. Lymphocytes of donors belonging to this subgroup showed significantly lower inhibition of cell cycle after irradiation.
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