Role of CXCR4 and SDF1 as prognostic factors for survival and the association with clinicopathology in colorectal cancer: A systematic meta-analysis.

C-X-C chemokine receptor type 4 and stromal cell-derived factor-1 were proven to play important roles in several types of cancer and in many biological processes connected with tumor growth, invasion, angiogenesis, and metastasis. However, the clinical significance of C-X-C chemokine receptor type 4 and stromal cell-derived factor-1 expression in colorectal cancer remains inaccurate. The purpose of this systematic meta-analysis is to investigate the role of C-X-C chemokine receptor type 4 and stromal cell-derived factor-1 as prognostic factors for survival and the association between C-X-C chemokine receptor type 4/ stromal cell-derived factor-1 and clinicopathology in colorectal cancer. Databases including PubMed, EMBASE, and Cochrane Library were searched for relevant literatures updated till January 2017. Review Manager 5.3 was used for data analysis. In our meta-analysis, C-X-C chemokine receptor type 4 expression is related to tumor-node-metastasis stage, tumor differentiation, liver metastasis, lymph node metastasis, distant metastasis, and diagnosis, and no correlation of C-X-C chemokine receptor type 4 expression with tumor size, gender, preoperative carcinoembryonic antigen, age, or vascular invasion has been observed. Stromal cell-derived factor-1 expression has no relationship with tumor-node-metastasis stage, lymph node metastasis, vascular invasion, age, gender, distant metastasis, or diagnosis. The expression of stromal cell-derived factor-1 has association with tumor differentiation. Moreover, the pooled hazard ratio for disease-free survival/overall survival showed that overexpression of C-X-C chemokine receptor type 4/stromal cell-derived factor-1 reduced disease-free survival/overall survival in colorectal cancer. Therefore, High expression of C-X-C chemokine receptor type 4/stromal cell-derived factor-1 which is essential in tumor progression can predict poor survival that may provide more advance prognostic clues to colorectal cancer patients.

4-Hydroxynonenal promotes growth and angiogenesis of breast cancer cells through HIF-1α stabilization.

4-Hydroxynonenal (4-HNE) is a stable end product of lipid peroxidation, which has been shown to play an important role in cell signal transduction, while increasing cell growth and differentiation. 4-HNE could inhibit phosphatase and tensin homolog (PTEN) activity in hepatocytes and increased levels have been found in human invasive breast cancer. Here we report that 4-HNE increased the cell growth of breast cancer cells as revealed by colony formation assay. Moreover, vascular endothelial growth factor (VEGF) expression was elevated, while protein levels of hypoxia inducible factor 1 alpha (HIF-1α) were up-regulated. Sirtuin-3 (SIRT3), a major mitochondria NAD+-dependent deacetylase, is reported to destabilize HIF-1α. Here, 4-HNE could inhibit the deacetylase activity of SIRT3 by thiol-specific modification. We further demonstrated that the regulation by 4-HNE of levels of HIF-1α and VEGF depends on SIRT3. Consistent with this, 4-HNE could not increase the cell growth in SIRT3 knockdown breast cancer cells. Additionally, 4-HNE promoted angiogenesis and invasion of breast cancer cells in a SIRT3-dependent manner. In conclusion, we propose that 4-HNE promotes growth, invasion and angiogenesis of breast cancer cells through the SIRT3-HIF-1α-VEGF axis.

Treatment of advanced rectal cancer after renal transplantation.

Renal transplantation is a standard procedure for end-stage renal disease today. Due to immunosuppressive drugs and increasing survival time after renal transplantation, patients with transplanted kidneys carry an increased risk of developing malignant tumors. In this case report, 3 patients with advanced rectal cancer after renal transplantation for renal failure were treated with anterior resection or abdominoperineal resection plus total mesorectal excision, followed by adjuvant chemotherapy. One patient eventually died of metastasized cancer 31 mo after therapy, although his organ grafts functioned well until his death. The other 2 patients were well during the 8 and 21 mo follow-up periods after rectal resection. We therefore strongly argue that patients with advanced rectal cancer should receive standard oncology treatment, including operation and adjuvant treatment after renal transplantation. Colorectal cancer screening in such patients appears justified.

Irinotecan or oxaliplatin combined with 5-fluorouracil and leucovorin as first-line therapy for advanced colorectal cancer: a meta-analysis.

BACKGROUND: To compare clinical efficacy and toxicity of irinotecan combined with 5-fluorouracil and leucovorin with those of oxaliplatin combined with 5-fluorouracil and leucovorin as first-line therapy for advanced colorectal cancer. METHODS: Literature search was performed by keywords "irinotecan", "oxaliplatin" and "colorectal cancer" on all randomized controlled trails reported on irinotecan versus oxaliplatin combined with 5-fluorouracil and leucovorin as first-line therapy for advanced colorectal cancer in MEDLINE, OVID, Springer, Cochrane Controlled Trials Register (CCTR) and CBMdisc (Chinese Biology and Medicine disc) before January 2010. Two authors drew the details of trial design, characteristics of patients, outcomes, and toxicity from the studies included. Data analysis was performed by RevMan 4.2. RESULTS: According to the screening criteria, 7 clinical studies with 2095 participants of advanced colorectal cancer were included in this meta analysis. The baseline characteristics of irinotecan group were similar to those of oxaliplatin group. The response rate of oxaliplatin group was higher than that of irinotecan group (relative risk (RR) = 0.82, 95% confidence interval (95%CI) (0.70, 0.96), P = 0.01), and the median overall survival of oxaliplatin group was longer by 2.04 months than that of irinotecan group (95%CI (-3.54, -0.54), P = 0.008). In the comparison of grade 3 - 4 toxicity between the two groups, the incidences of nausea, emesis, diarrhoea and alopecia in irinotecan group were higher than those in oxaliplatin group (RR = 1.94, 95%CI (1.22, 3.09), P = 0.005; 1.71, 95%CI (1.34, 2.18), P < 0.001; 14.56, 95%CI (4.11, 51.66), P < 0.0001), respectively. However, the incidence of neurotoxicity, neutropenia and thrombocytopenia in irinotecan group were lower than those in oxaliplatin group (RR = 0.06, 95%CI (0.03, 0.14), P < 0.00001; 0.70, 95%CI (0.55, 0.91), P = 0.006; 0.18, 95%CI (0.05, 0.61), P = 0.006), respectively. CONCLUSIONS: Both irinotecan and oxaliplatin combined with 5-fluorouracil and leucovorin were effective in the first-line therapy of advanced colorectal cancer. However, the combined regimen of oxaliplatin plus 5-fluorouracil and leucovorin is more excellent. Irinotecan tended to result in more gastrointestinal tract reactions than oxaliplatin did, but the myelosuppression and neurotoxicity were more frequent in oxaliplatin regimen than irinotecan regimen.

[Efficacy of preoperative radiotherapy combined with total mesorectal excision in the treatment of locally resectable rectal cancer: a systematic review].

OBJECTIVE: To assess the clinical efficacy of preoperative radiotherapy combined with total mesorectal excision (TME) in the treatment of locally resectable rectal cancer. METHODS: Literature search was carried out to identify prospective clinical randomized controlled trails on preoperative radiotherapy for rectal cancer published from January 1982 to April 2009. The basic characteristics and clinical efficacy of the trials meeting the screening criteria were enrolled. Date analysis was performed by RevMan 4.2. RESULTS: According to the selection criteria, 9 clinical trials were included. Compared with surgery alone, the short-term preoperative radiotherapy was associated with reduced 2-year local recurrence rate (2.4% vs 8.2%, P<0.01). There were no significant differences in 4-year overall survival (67.2% vs 66.2%), 4-year disease-free survival (58.4% vs 55.6%) and local recurrence (RR=1.16, 95% CI:0.37~3.61, P=0.80) between the preoperative radiotherapy and radiochemotherapy. High-dose preoperative radiotherapy could increase the complete response rate and sphincter sparing surgery rate than that low-dose (16.0% vs 2.0%, P<0.05). The interval between preoperative radiotherapy and operation did not affect the overall survival, disease-free survival and local recurrence. CONCLUSION: Preoperative radiotherapy combined with total mesorectal excision is associated with lower local recurrence.

[Study on the prognostic factors of colorectal cancer after radical resection and on suggested model for prediction].

OBJECTIVE: To study the factors of colorectal cancer (CRC) after radical resection to provide data predicting the prognosis of the patients. METHODS: 120 cases of CRC were collected in this study. Medical clinical records and 5-year follow-up data were reviewed. Streptavidin-peroxidase immunohistochemical technique was used to detect the expression of p53, C-erbB-2, nm23-H(1) and Ras on formalin-fixed, paraffin embedded sections of CRC from the 120 patients. RESULTS: Results showed that the rates of positive expression of p53, C-erbB-2, Ras and nm23-H(1) were 62.5% (75/120), 25.8% (31/120), 80.0% (96/120) and 60.8% (73/120) respectively in the CRC tissue. All pathological variables and biological markers were analyzed with Cox regression model (alpha = 0.05). Eight distinguished prognostic factors were identified in the univariate analysis as: macroscopic configuration, histology grade, depth of invasion of intestinal, lymph nodes metastasis, Dukes' classification, p53, Ras and nm23-H(1). The results of multivariate analysis (alpha = 0.05) indicated that the independent prognostic factors were Dukes' classification, p53 and nm23-H(1) (P = 0.000), with relative risk of 3.06, 6.02 and 0.40, respectively. A prognostic model: h(t, x) = h(0)(t)exp (-0.9269X(14) + 1.1197X(10) + 1.7948X(11)) was established. Sensitivity, specificity agreement and reliability of the model and Kappa were 79.1%, 83.0%, 80.8% and 0.62, respectively. CONCLUSION: Dukes' classification, p53 and nm23-H(1)seemed to be independent and important prognostic factors. This prognostic model could be used to evaluate the prognosis of patients with CRC by clinicians.