BackgroundThe aim of the study was to assess the impact of CD133-positive (CD133+) cancer stem cell proportions on treatment results of glioblastoma multiforme (GBM) patients.Patients and methodsPatients with GBM (n = 42) received postoperative radiotherapy (± chemotherapy). Surgically excised GBM tissue sections were immunohistochemically examined for CD133 expression. The proportions of CD133+ GBM cells were determined (%). The proportion of CD133+ GBM stem cells was established by 2 independent researchers whose results were in good accordance (R = 0.8, p < 0.01). Additionally, CD133 expression levels were correlated with patients overall survival.ResultsThe proportion of CD133+ cells varied between patients, being from 0.5% to 82%. Mean and median proportions of CD133+ cells of the entire study group were 33% ± 24% (mean ± SD) and 28%, respectively. Clinical data do not support the association between higher proportion of stem cells and the aggressiveness of GBM. Median survival time of the study group was 10.0 months (95% CI 9.0–11.0). The survival time clearly depended on the proportion of CD133+ cells (log rank test, p = 0.02). Median survival times for patients with low (< median) and high (≥ median) proportion of CD133+ cells were 9.0 months (95% CI 7.6–10.5) and 12.0 months (95% CI 9.3–14.7), respectively. In multivariate analysis, the proportion of CD133+ cells emerged as a significant independent predictor for longer overall survival (HR 2.0, 95% CI 1.0–3.8, p = 0.04).ConclusionsIn patients with higher stem cell proportion, significantly longer survival times after postoperative radiotherapy were achieved. Underlying reasons and possible higher sensitivity of GBM stem cells to fractionated radio-therapy should be clarified in further studies.

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Abstract. Lung cancer is the malignant disorder associated with a high number of fatalities in women and men worldwide. Despite continuous improvements in diagnostic strategies and therapeutic modalities over the past decades, the prognosis and survival rate of patients suffering from lung cancer are still unsatisfactory and suggest the requirement for further molecular studies with different lung cancer models. In the present study, the anticancer action of two methylated metabolites of quercetin, isorhamnetin and tamarixetin, was assessed by studying their antiproliferative and apoptosis-inducing potential in human lung adenocarcinoma cell lines, A549 and HCC-44. Both methylquercetins decreased the viability of lung cancer cells at doses significantly lower than those effective for parent quercetin. The IC 50 values measured for isorhamnetin were 26.6 and 15.9 µM in A549 and HCC-44 cells, respectively. For tamarixetin, the IC 50 values were 19.6 and 20.3 µM in A549 and HCC-44 cells, respectively. These results were many-fold lower than the respective values for quercetin (72.2 and 107.6 µM for A549 and HCC-44 cells, respectively). Based on the activation of caspase family members, both metabolites induced apoptotic cell death in the tested cell lines, predominantly via the extrinsic pathway in A549 cells and in both intrinsic and extrinsic pathways in HCC-44 cells. As A549 and HCC-44 lines were originally established from a male and female patient, current data may suggst some gender differences in the action of quercetin derivatives. Addition of a methyl group in the 3'-or 4'-position of the B-ring of quercetin significantly increased the anticancer activity of this flavonol towards lung adenocarcinoma cells, which demonstrated that these compounds may be considered as potential novel candidates for the development of future chemotherapeutics in the fight against lung cancer.

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Background/Aim: More than half of prostate cancer patients use, in addition to conventional therapies, some kind of complementary medicine, including flavonoidrich products. However, knowledge about the co-effects of flavonoids with cytotoxic chemotherapies is still rather poor. Therefore, this study was undertaken to assess the cytotoxic activity of flavonoids and their interactions with taxanes in human advanced prostate cancer cells. Materials and Methods: Cytotoxicity of different flavonoids and their effects on the efficacy of docetaxel and cabazitaxel were studied in the human metastatic prostate cancer cell line PPC-1, using MTT colorimetric assay. Results: Both taxanes suppressed the viability of PPC-1 cells with IC 50 values in the nanomolar range. Tested flavonoids exerted cytotoxic activity only at high micromolar concentrations or revealed no remarkable effect on cell survival. Simultaneous treatment of cells with taxanes and flavonoids baicalein, chrysin, luteolin, fisetin, quercetin, genistein or daidzein did not lead to any change in chemotherapy-induced cytotoxicity. However, simultaneous exposure of cells to hesperetin and taxanes resulted in 9.8-and 13.1-fold reduction in cytotoxicity of docetaxel and cabazitaxel, respectively. Conclusion: Flavonoid hesperetin remarkably suppressed the cytotoxic efficacy of taxanes in prostate cancer cells. Therefore, caution is required from prostate cancer patients who take hesperetin-containing oral supplements.Prostate cancer is the most common malignancy among men worldwide. According to GLOBOCAN, about 1.1 million new cases and 307,000 deaths were recorded in 2012, making it thus the third-leading cause of cancer-related death in men (1, 2). Although treatment with radiation and surgery can be curative in localized organ-confined prostate tumors, more than one third of patients progress to metastatic disease (3, 4). For these men, androgen deprivation therapy is the standard of care (3). However, after initial remission in most patients, tumor eventually develops into castration-resistant disease (5). Chemotherapy with taxane (docetaxel or cabazitaxel) is currently considered one of the effective treatment options for advanced castration-resistant prostate cancer that exerts its anti-tumor activity through direct antimitotic effects as well as by suppressing the microtubuledependent trafficking of proteins like androgen receptors (6). Despite effective anti-cancer therapies, more than half of prostate cancer patients use additionally some kind of complementary medicines (CM), whereas the majority of patients believe that CM are "helpful" or "very helpful" for their condition (7). This is somewhat surprising since conclusive evidence regarding the use of CM is still lacking and current knowledge relies mostly on few experimental studies performed with cancer cell lines and/or animal models. Furthermore, interactions of CM with conventional anti-cancer therapies, including taxane-based chemotherapy in prostate cancer, are largely unknown.Previous studies hav...