Docetaxel, cisplatin, and 5-fluorouracil compared with epirubicin, cisplatin, and 5-fluorouracil regimen for advanced gastric cancer: A systematic review and meta-analysis.

BACKGROUND: As the first-line regimens for the treatment of advanced gastric cancer, both docetaxel, cisplatin, and 5-fluorouracil (DCF) and epirubicin, cisplatin, and 5-fluorouracil (ECF) regimens are commonly used in clinical practice, but there is still controversy about which is better. AIM: To compare the efficacy and safety of DCF and ECF regimens by conducting this meta-analysis. METHODS: Computer searches in PubMed, EMBASE, Ovid MEDLINE, Science Direct, Web of Science, The Cochrane Library and Scopus were performed to find the clinical studies of all comparisons between DCF and ECF regimens. We used progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and adverse effects (AEs) as endpoints for analysis. RESULTS: Our meta-analysis included seven qualified studies involving a total of 598 patients. The pooled hazard ratios between the DCF and ECF groups were comparable in PFS (95%CI: 0.58-1.46, P = 0.73), OS (95%CI: 0.65-1.10, P = 0.21), and total AEs (95%CI: 0.93-1.29, P = 0.30). The DCF group was significantly better than the ECF group in terms of ORR (95%CI: 1.13-1.75, P = 0.002) and DCR (95%CI: 1.03-1.41, P = 0.02). However, the incidence rate of grade 3-4 AEs was also greater in the DCF group than in the ECF group (95%CI: 1.16-1.88, P = 0.002), especially for neutropenia and febrile neutropenia. CONCLUSION: With better ORR and DCR values, the DCF regimen seems to be more suitable for advanced gastric cancer than the ECF regimen. However, the higher rate of AEs in the DCF group still needs to be noticed.

Isolation and phenotypic characterization of cancer stem-like side population cells in colon cancer.

Previous studies in cancer biology suggest that chemotherapeutic drug resistance and tumor relapse are driven by cells within a tumor termed 'cancer stem cells'. In the present study, a Hoechst 33342 dye exclusion technique was used to identify cancer stem­like side population (SP) cells in colon carcinoma, which accounted for 3.4% of the total cell population. Following treatment with verapamil, the population of SP cells was reduced to 0.6%. In addition, the sorted SP cells exhibited marked multidrug resistance and enhanced cell survival rates compared with non­SP cells. The SP cells were able to generate more tumor spheres and were CD133 positive. Subsequent biochemical analysis revealed that the levels of the adenosine triphosphate­binding cassette sub­family G member 2 transporter protein, B­cell lymphoma anti­apoptotic factor and autocrine production of interleukin­4 were significantly enhanced in the colon cancer SP cells, which contributed to drug resistance, protection of the cells from apoptosis and tumor recurrence. Therefore, the findings suggested that treatment failure and colon tumorigenesis is dictated by a small population of SP cells, which indicate a potential target in future therapies.

Effects of siRNA targeting BMPR-II on the biological activities of human liver cancer cells and its mechanism.

BACKGROUND: Bone morphogenetic protein receptor II (BMPR-II) plays an important role in tumor's invasion and proliferation. In this study, we observed the effects of small interfering RNA (siRNA) targeting bone morphogenetic protein receptor II (BMPR-II) on the biological activities of human liver cells and explore its mechanism. METHODS: The molecular sequences of three siRNA targeting BMPR-IIwere designed and synthesized. In this study, there were 6 groups including group I (normal control), group II (blank control), group III (negative control) and group IV-VI (BMPR-II-siRNA-a, siRNA-b and siRNA-c-transfected cells, respectively). The levels of mRNA and protein of BMPR-II were determined to select the best sequence for BMPR-II silence. After liver cancer cells were transfected with the best sequence, proliferation and invasion of transfected cells were assessed, and apoptosis and cell cycle were detected. The expressions of mitogen-activated protein kinases (MAPKs) signal pathway-related VEGF-C protein were observed after BMPR-II silence and BMPR-II silence combined with inhibiting MAPKs signal pathway, respectively. RESULTS: RT-PCR and Western blot indicated that BMPR-II expression was the highest in HepG2 among the three liver cancer lines (P < 0.01) and the lowest in group IV among the six groups (P < 0.01). MTT assay and transwell assay revealed that the numbers of cell growth and cell transmembrane were significantly lower in group IV than in control groups 48 h after cells were transfected (P < 0.05). Flow cytometer showed that apoptosis was the highest and cells were significantly blocked in S phase 48 h after cells were transfected in group IV (P < 0.01). Western blot indicated that the protein levels of p-P38 (P < 0.01) and vascular endothelial growth factor-C (VEGF-C) (P < 0.01) were significantly decreased after BMPR-II silence. The protein level of VEGF-C was significantly decreased in PD98059 + siRNA-BMPR-II-a and SB203580 + siRNA-BMPR-II-a groups (P < 0.01), especially in SB203580 + siRNA-BMPR-II-a group (P < 0.01). CONCLUSIONS: siRNA targeting BMPR-IIcan markedly inhibit HepG2 proliferation and invasion, promote apoptosis and block HepG2 in S phase. Its mechanism may be that BMPR-II silence down-regulates VEGF-C expression through MAPK/P38 and MAPK/ERK1/2 pathways, especially MAPK/P38. This study provides a new targeted therapy for liver cancer.

The utility of platelet, mean platelet volume, and red cell distribution width in the diagnosis of active Crohn's disease and intestinal tuberculosis.

OBJECTIVE: To evaluate the diagnostic utility of platelet count (PLT), mean platelet volume (MPV), and red cell distribution width (RDW) in patients with active Crohn's disease (CD) and intestinal tuberculosis (ITB). METHODS: This study was conducted in the Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, China. Sixty-eight patients with active CD, 35 with ITB, and 22 as control group were recruited. Blood routine test including white blood cell, red blood cell, PLT, MPV, RDW, and so forth was investigated. RESULTS: Patients with active CD and ITB have increased PLT and RDW (both p<0.001), and decreased MPV (p=0.002). The RDW performed preferably in predicting both active CD (odds ratio [OR]=2.390, p=0.007), and ITB (OR=2.338, p=0.017), and had better diagnostic value (area under the receiver operating characteristics curve [AUC] - 0.812; p<0.001) than CRP (AUC - 0.716; p=0.007) and ESR (AUC - 0.804; p<0.001) in ITB diagnosis. CONCLUSION: Among the laboratory markers, RDW not only possessed the favorable capability to predict active CD, but also showed outstanding predicting capability, and good diagnostic value in ITB.

Utility of in vitro interferon-γ release assay in differential diagnosis between intestinal tuberculosis and Crohn's disease.

OBJECTIVE: To evaluate the diagnostic utility of interferon-γ release assay (T-SPOT.TB) for the differential diagnosis between Crohn's disease (CD) and intestinal tuberculosis (ITB). METHODS: A total of 103 CD and 88 ITB patients, confirmed by histology and anti-tuberculosis treatment response from 2003 to 2011, were included. Their characteristics and clinical features were recorded. Mycobacterium tuberculosis (MTB) polymerase chain reaction (PCR) of IS6110, in vitro T-SPOT.TB, tuberculin skin test (TST), immunoglobulin G (IgG) antibody to MTB (protein chip), serum anti-Saccharomyces cerevisiae antibodies (ASCA IgG, chronic inflammatory bowel disease profile) and acid-fast staining of biopsied colonic tissue specimens were performed. Statistical analysis was conducted to determine their concordance with the diagnosis and its sensitivity, specificity, positive (PPV) and negative predictive value (NPV). RESULTS: Abnormal pulmonary X-ray, ascites and lesions of both cecum and ascending colon were more associated with ITB, while intestinal surgery and lesions of both ileum and adjacent colon were more commonly seen in CD. Significant diagnostic concordance was found using T-SPOT.TB (κ = 0.786) by consistency test. The sensitivity, specificity, PPV and NPV of T-SPOT.TB were 86%, 93%, 88% and 91%, respectively, and the sensitivity and NPV were significantly higher than other examinations (P < 0.05). CONCLUSION: T-SPOT.TB is a valuable assay in differentiating ITB from CD, particularly in the diagnostic exclusion of ITB based on its high specificity and NPV.

[The relationship between major histocompatibility complex class I chain-related antigens A (MICA)-129 gene polymorphism, soluble MICA level and ulcerative colitis].

OBJECTIVE: To investigate the association of the major histocompatibility complex class I chain-related antigens A (MICA)-129 gene polymorphism and soluble MICA (sMICA) levels with ulcerative colitis (UC) in Hubei Han nationality. METHODS: The genetic polymorphism of MICA-129 was examined using a polymerase chain reaction-sequence based test (PCR-SBT) in 256 UC patients and 460 healthy controls. From the above subjects, 80 patients and 90 healthy individuals were randomly selected for determining serum sMICA concentrations by ELISA. RESULTS: The frequencies of variant allele (G) and genotype (GG) in MICA-129 gene were significantly higher in the UC patients than in the controls (76.8% vs 72.2%, P = 0.060; 55.9% vs 46.3%, P = 0.016). Serum sMICA levels were significantly elevated in the patients compared to the controls [(576.47 ± 279.02) ng/L vs (182.17 ± 73.11) ng/L, P < 0.001]. In addition, the sMICA levels were higher in the patients carrying MICA-129 GG genotypes than in those carrying (GA + AA) genotypes [(638.87 ± 347.15) ng/L vs (507.51 ± 152.87) ng/L, P = 0.035]. CONCLUSIONS: The genetic polymorphism of MICA-129 and sMICA levels are correlated with the UC patients in Hubei Han nationality. Our findings demonstrate that MICA-129 gene may contribute to the pathogenesis of UC.