Crowdermunck1013

Mammalian target of rapamycin (mTOR) has two subtypes, i.e., mTORC1 and mTORC2, which contain the Raptor and Rictor core molecules, respectively. The effect of Raptor and Rictor on hypoxia inducible factor (HIF)-1α, HIF-2α, and vascular endothelial growth factor (VEGF) in colorectal cancer (CRC) is unclear. In this work, we investigated the correlations among Raptor, Rictor, HIF-1α, HIF-2α, and VEGF expression in CRC. We subsequently analyzed the clinicopathological features of patients. Immunohistochemistry, western blot, and RT-PCR analyses were performed to detect the expression of Raptor, Rictor, HIF-1α, HIF-2α, and VEGF in 120 cases of CRC and 60 cases of normal colorectal mucosa. CD34 was used to label microvascular density (MVD), which was found to be higher in patients with positive Raptor or Rictor than in those with negative Raptor or Rictor. The positive rates of Raptor, Rictor, HIF-1α, HIF-2α, and VEGF in CRC were significantly higher than in normal colorectal mucosa. Raptor expression was positively correlated with HIF-1α and VEGF but not with HIF-2α expression. By contrast, Rictor expression was positively correlated with HIF-2α and VEGF but not with HIF-1α expression. Survival analysis further indicated that Raptor, Rictor, HIF-1α, HIF-2α, VEGF and lymph node metastasis were independent prognostic factors in CRC. To conclude, Raptor and Rictor expression was related to the initiation and development of CRC and angiogenesis in different ways. The combined detection of Raptor and Rictor is important for patients with colorectal carcinoma in prognosis and optimal therapy.Despite advances in multimodal approach for rectal cancer, treatment-related side effects remain an important issue. From this perspective, a prospective trial was performed to investigate the feasibility of modulated electro-hyperthermia (mEHT) as a concomitant boost to preoperative chemoradiation in locally advanced rectal cancer. Seventy-six patients with cT3-4 or cT2N+ rectal cancer were enrolled consecutively. Whole pelvis radiotherapy of 40 Gy was delivered with 2-Gy daily fraction. mEHT with 13.56 MHz frequency was boosted on a twice-weekly schedule concurrently with intravenous 5-fluorouracil or oral capecitabine. Surgical resection was planned 6-8 weeks after radiotherapy. The primary endpoint was non-inferior treatment response rate assessed by pathologic downstaging and tumor regression. The secondary endpoint was acceptable toxicity during the preoperative treatment period. Sixty patients completed the planned treatment schedule. T- and N-downstaging was demonstrated in 40 patients (66.7%) and 53 patients (88.3%), respectively. GSK1904529A Pathologic complete response was noted in 15.0% (9 patients) and 76.7% (46 patients) for T-stage and N-stage, respectively. Total or near total tumor regression was observed in 20 patients (33.3%). Grade ≥ 3 toxicity occurred only in hematologic assessment; one case (1.7%) of leukopenia and one case (1.7%) of anemia. Sixteen patients (26.7%) developed thermal toxicity, which was mostly Grade 1 (15 patients, 93.8%). Relatively low dose of 40 Gy radiation showed comparable pathologic treatment outcomes and tolerable toxicity profiles with the addition of mEHT, which may potentially replace part of the radiation dose in neoadjuvant treatment for rectal cancer.Interleukin-18 (IL-18) is a multifunctional cytokine that augments interferon-γ production, promotion of the Th1 immune response and acts as an important immunomediator in the development of some cancers. The current study aimed to analyze the association of five most common polymorphisms in IL-18 gene with prostate cancer in Iranian population. We examined a possible association of IL-18 -137G>C, -607C>A, -656G>T, +105A>C and +127C>T polymorphisms with prostate cancer occurrence by PCR-RFLP assay. Odds ratio (OR) and 95% confidence interval (CI) were used to assess the strength of the association between IL-18 polymorphisms and prostate cancer. Statistical analysis revealed that individuals carrying the mutant homozygote genotype of IL-18 -607C>A (OR  =  2.251, 95% CI  =  1.062-4.768, P = 0.034) and -137G>C (OR  =  2.364, 95% CI  =  1.121-4.984, P = 0.024) polymorphisms had an increased risk of prostate cancer. However, for IL-18 -656G>T, +105A>C and +127C>T polymorphisms, there were no differential distributions of their genotypes between patients with prostate cancer and healthy subjects. Our results indicated that the IL-18 -137G>C and -607C>A polymorphisms were significantly associated with an increased risk of prostate cancer in Iranian population. Thus, these polymorphisms might be used as a molecular biomarker in the early diagnosis of prostate cancer.Multidrug resistance (MDR) in breast cancer treatment is the major cause leading to the failure of chemotherapy. P-glycoprotein (P-gp), the product of the human MDR1 gene, plays a key role in resistance to chemotherapy and confers a cross-resistance to many structurally unrelated anticancer drugs. We previously have reported that integrin αvβ6 plays a critical role in breast cancer invasion and metastasis. However, whether and how αvβ6 is associated with P-gp and regulated by potential genetic mechanisms in breast cancer still remains unclear. In the present study, we further investigated the reversal effect and underlying mechanisms of MDR in breast cancer. Two small interfering RNA constructs (pSUPER-β6shRNAs) targeting two different regions of the β6 gene have been designed to inhibit αvβ6 expression by transfecting them into adriamycin-resistant MCF-7/ADR cell lines. Suppression of αvβ6 dramatically downregulated the levels of MDR1 gene mRNA and P-gp. In particular, β6shRNA-mediated silencing of αvβ6 gene increased significantly the cellular accumulation of Rhodamine 123 and markedly decreased drug efflux ability, suggesting that β6shRNAs indeed inhibit P-gp mediated drug efflux and effectively overcome drug resistance. In addition, inhibition of integrin αvβ6 supressed the expression of ERK1/2. Interestingly, our data demonstrate that suppression of integrin αvβ6 caused significant downregulation of Bcl-2, Bcl-xL and upregulation of caspase 3, Bad, especially which were accompanied by increasing activity of cytochrome C. A possible connection between αvβ6 and P-gp in drug resistance biology is suggested. Taken together, β6shRNA could efficiently inhibit αvβ6 and MDR1 expression in vitro and these findings may offer a specifically useful means to reverse MDR in breast cancer therapy.