Northklemmensen1322

ions There is a large difference in gene expression profiles between AFP(high) and AFP(low) HCC. The prognostic signature may cooperate with AFP to promote the initiation and development of HCC. It also may explain the tumorigenesis in HCC with different AFP levels, and provide new clues for the prognosis of HCC.Objective To investigate the expression of IGF1R-Ras and RAGE-HMGB1 signaling pathways in colorectal cancer patients with type 2 diabetes mellitus and their significance. Methods The resected cancer tissues were obtained from 59 patients with colorectal cancer (CRC), including 29 patients with type 2 diabetes mellitus (CRC/DM group) and 30 with CRC alone (CRC group). The expressions of IGF1R, Ras, RAGE and HMGB1 in cancer tissues were detected by immunohistochemistry. The differences between the two groups were compared and the relationship between the expression and clinicopathological characteristics was analyzed. Results In CRC/DM group, the positive rates of IGF1R and Ras were both 65.5% (19/29), and 51.7% (15/29) patients had IGF1R+ Ras+ immunophenotype, which were significantly higher than those in CRC group [33.3% (10/30), 36.7% (11/30) and 20.0% (6/30); P=0.013, 0.027 and 0.011, respectively]. The expression of IGF1R and Ras in CRC / DM group was positively correlated (r=0.479, P=0.017). The positive rate of RAGE expression in CRC group and CRC/DM group was 70.0% (21/30) and 72.4% (21/29) respectively, and the positive rate of HMGB1 expression was 46.7% (14/30) and 58.6% (17/29) respectively, neither was observed with significant difference (P=0.358 and 0.838). However, the proportion of patients with RAGE+ HMGB1+ immunophenotype in CRC/DM group [55.2% (16/29)] was higher than that in CRC Group [26.7% (8/30)] which was statistically significant (P=0.026), and the expression of both proteins was positively correlated in CRC/DM group (r=0.578, P=0.003). The clinicopathological analysis showed that in both groups the expression of IGF1R, Ras, RAGE and HMGB1 had no correlation with the sex, age, differentiation degree, tumor length, T stage and lymph node metastasis (P>0.05). Conclusion Both IGF1R-Ras and RAGE-HMGB1 pathways may be involved in the oncogenesis of colorectal cancer in patients with type 2 diabetes.Objective To examine the expression of T-box5 (TBX5) in colorectal cancer tissues and its clinical significance, and explore the effects of TBX5 on the invasion and metastasis of colorectal cancer cells and its mechanism. Methods The expressions of TBX5 in cancer and adjacent normal tissues were tested by immunohistochemistry (IHC), and the relationship between TBX5 and clinicopathological features and prognosis of colorectal cancer was analyzed. Real-time quantitative PCR (RT-qPCR) and western blot were used to detect the expressions of TBX5 in different colorectal cancer cell lines. TBX5 overexpression plasmid was constructed and transfected into human colorectal cancer cell line HT-29, and cell counting kit-8 (CCK-8) was used to detect the activities of transfection HT-29 cells. Cell scratch test and Transwell assay were used to detect the migration and invasion abilities of cells, while RT-qPCR and western blot were used to detect the mRNA and protein expressions of PCNA, p21, p16, p27, MMP-2, MMP-7 and TIMP-1. Results The positive rate of TBX5 protein in colorectal cancer tissues was 24.44% (22/90), significantly lower than 65.56% of adjacent normal tissues (P0.05). Conclusions Downregulation of TBX5 is a marker of poor prognosis in patients with colorectal cancer. TBX5 may inhibit the progression of colorectal cancer by inhibiting proliferation, invasion and metastasis related genes.Objective To investigate the associations between the genetic variations of apoptosis genes and the adverse events of postoperative concurrent chemoradiotherapy in patients with rectal cancer. Methods We enrolled 362 patients with stage Ⅱ to Ⅲ rectal cancer who received concurrent chemoradiotherapy. Whole blood sample (2 ml) was collected from patient at the time of enrollment before therapy. Sequenom MassARRAY was used to detect the genotypes of 29 haplotype-tagging single nucleotide polymorphisms (htSNPs) in eight apoptosis genes, including Fas cell surface death receptor(FAS), Fas ligand(FASL), apoptotic peptidase activating factor 1(APAF1), BCL2 associated X(BAX), TNF-related apoptosis-inducing ligand(TRAIL), TNF-related apoptosis-inducing ligand receptor 1(TRAILR1), TNF-related apoptosis-inducing ligand receptor 2(TRAILR2) and caspase-7(CASP7). The associations between genotypes and adverse events of chemoradiotherapy were measured by unconditional logistic regression model. Results Three hundred and six7). The remaining SNPs were not related to the adverse events of chemoradiotherapy (all P>0.05). Grade≥2 myelosuppression occurred less frequently in male than in female (P=0.046); Surgical treatment and tumor location had great impact on the occurrence of grade≥2 diarrhea (all P less then 0.001) and dermatitis (all P less then 0.05). Conclusions The genetic variations of FAS, APAF1, BAX, TRAIL and CASP7 are related to the adverse events of concurrent chemoradiotherapy in patients with rectal cancer, which may be potential genetic biomarkers for individualized treatment of rectal cancer.Objective To investigate the effects and the mechanism of FoxO6 on the proliferation and invasion of colorectal cancer cells. Methods FoxO6 siRNA was transfected into colorectal cancer cell HCT116 and SW480. The overexpression vector pcDNA.3.1-c-Myc was constructed and co-transfected into HCT116 and SW480 cells with FoxO6 siRNA. Real-time fluorescent quantitative PCR (RT-qPCR) and western blot were used to detect the mRNA and protein expressions of FoxO6, c-Myc, and p21 in HCT116 and SW480 cells. Bromodeoxyuridine (BrdU) was used to detect cell proliferation and Transwell assay was performed to detect the invasion ability of these cells. SW480 cells transfected with FoxO6 shRNA lentivirus (LV-FoxO6) and were injected into the right armpit of BAL b/c nude mice to construct a tumor-bearing mode and the tumor volumes were measured on the days of 10, 13, 16, 19, 22, and 25 after injection. Results The FoxO6 mRNA were 0.91±0.04, 1.72±0.07, and 2.03±0.06, and protein expression were 0.70±0.04, 1.35±0.08, and 1.56±0tumor volume of LV-FoxO6 group was (190.6±36.2) mm(3), significantly lower than (437.8.6±69.2) mm(3) of LV-NC group (P less then 0.05). Conclusion FoxO6 promotes the proliferation and invasion of colorectal cancer cells through facilitating c-Myc mediated p21 expression inhibition.Objective To investigate the effect of silencing hepatocyte growth factor receptor (c-Met) expression on the biological characteristics of HCT116 colon cancer cells. Methods Cellular model of c-Met transient transfection was established by using small interfering RNA (siRNA), the expression of c-Met in colon cancer cells was detected by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) and western blot. The apoptosis assay, cell invasion assay, cell migration and other experiments were conducted to observe the effects of silencing c-Met on the biological characteristics of colon cancer cells. Results RT-qPCR results showed that the relative expression levels of c-Met mRNA in siRNA-Met group, blank control group and siRNA negative control (siRNA-NC) group were 0.32±0.26, 1.01±0.03 and 1.05±0.23, respectively, and the difference was statistically significant (P less then 0.05). TAK-901 inhibitor Western blot analysis showed that the expression level of c-Met protein in the siRNA-Met group was 0.24±0.03, sigsignificantly decreased while Bcl-2 associated X protein (BAX) expression level was significantly increased. The cell scratching result showed that the cell migration abilities of the siRNA-Met group, blank control group and the siRNA-NC group were (51.33±8.62)%, (100.00±3.72)% and (102.33±6.43)%, respectively, and the difference was statistically significant (P less then 0.05). The number of cell penetrating into the basement membrane of the siRNA-Met group, blank control group and the siRNA-NC group were 47.50±10.60, 100.00±5.33 and 102.50±10.61, respectively, and the difference was statistically significant (P less then 0.05). The expressions of invasion related proteins including MMP-2 and MMP-9 in siRNA-Met group were decreased significantly. Conclusions c-Met plays an important role in maintaining the biological characteristics of colon cancer cells. Inhibition of c-Met may have important values in the treatment of colon cancer.Objective Breast cancer is a kind of malignant tumor which seriously endangers women's health. With the development of molecular biology technology and the further understanding of pathogenesis, the treatment of breast cancer has entered a new era of molecular targeted therapy, and has been making new progress. At present, molecular targeted drugs for the treatment of breast cancer keep emerging, mainly including endocrine therapy targeting estrogen and progesterone receptor (ER/PR), targeted drugs treatment for epidermal growth factor receptor-2 (HER-2); phosphatidylinositol 3 kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway inhibitors, anti-angiogenic drugs, poly (ADP-ribose) polymerase (PARP) inhibitors for BRCA1/2 mutations, cyclin-dependent kinases (CDK) 4/6 inhibitors, etc. Because some signal pathway abnormalities may occur in different molecular types of breast cancer, the same targeted drugs are cross-used in different types.Thiopurine has been used to maintain remission and to reduce antidrug antibody formation in monoclonal antibody therapy in patients with inflammatory bowel disease (IBD). The use of thiopurine is limited by side effects such as leukopenia. Thiopurine S-methyltransferase (TPMT) variants are associated with thiopurine-induced leukopenia in Westerners, but the frequency of the risk alleles is low in Asians. Recently, a variant in the nudix hydrolase 15 (NUDT15) gene (R139C, c415C > T) was reported to be associated with early severe leukopenia in Asians. NUDT15 is an enzyme that converts 6-thio-(deoxy)guanosine triphosphate (6-T(d)GTP) to 6-thio-(deoxy)guanosine monophosphate (6-T(d)GMTP). The R139C variant impairs the stability of the protein and increases incorporation of 6-TGTP and 6-TdGTP into RNA and DNA, respectively, resulting in leukopenia. The frequency of C/C, C/T, and T/T are approximately 80%, 20%, and 1%, respectively in East Asians. Early leukopenia occurred in less than 3% of patients with C/C and in around 20% of those with C/T, whereas it occurred in almost all patients with T/T. Patients homozygous for this variant also develop severe hair loss. The measurement of NUDT R139C can increase the safety of thiopurine dramatically and is a successful example of personalized medicine in the field of IBD.Congenital hyperinsulinism (CHI) is the most common cause of severe, persistent hypoglycemia in neonates and infants. Current available treatment is subtotal pancreatectomy if the patient does not respond to medical treatment but some of the patients still experience severe hypoglycemia after the surgery. Sirolimus, a mammalian target of rapamycin(mTOR) inhibitor recently has been reported to be effective in the treatment of insulinoma and CHI patients. Here we report a patient with CHI who had prolonged hypoglycemia after the subtotal pancreatectomy. The patient with a heterozygous mutation in ABCC8 was unresponsive to optimal dose of diazoxide (15 mg/kg/day) and octreotide (30µg/kg/day). The patient subsequently had subtotal pancreatectomy; however, the patient continued to have severe and persistent hypoglycemia. Sirolimus was commenced. Glycemic control had remarkable improvement without major adverse events, although he required a small dose of octreotide to maintain euglycemia. Sirolimus therapy was discontinued when the patient was 15 months old.