Association between ATM 5557G>A polymorphism and breast cancer risk: a meta-analysis.

Epidemiological studies have evaluated the association between ATM 5557G>A (p.D1853N) polymorphism and breast cancer risk. However, the results remain conflicting rather than conclusive. To derive a more precise estimation of the relationship, we performed this meta-analysis. Systematic searches of PubMed and Medline databases were performed. A total of nine studies included 3155 cases and 2752 controls were identified. When all nine studies were pooled into the meta-analysis, there was no evidence for significant association between 5557G>A mutation and breast cancer risk(for G/A vs. G/G: OR = 1.05, 95% CI = 0.83-1.34; for A/A vs. G/G: OR = 0.77, 95% CI = 0.58-1.03; for dominant model: OR = 1.04, 95% CI = 0.82-1.31; for recessive model: OR = 0.87, 95% CI = 0.69-1.09). In the subgroup analyses by family history and ethnicity, significant associations were found among Amerindians (for G/A vs. G/G: OR = 2.19, 95% CI = 1.38-3.47; for dominant model: OR = 2.15, 95% CI = 1.37-3.38). In summary, the meta-analysis suggest that ATM 5557G>A polymorphism is associated with increased breast cancer risk among Amerindians. However, due to the small subjects included in analysis and the selection bias existed in some studies, the results for Amerindians should be interpreted with caution.

Toremifene versus tamoxifen for advanced breast cancer.

BACKGROUND: Toremifene (TOR) and tamoxifen (TAM) can both be used as treatments for advanced breast cancer. OBJECTIVES: To compare the efficacy and safety of TOR with TAM in patients with advanced breast cancer. SEARCH METHODS: The Cochrane Breast Cancer Group's Specialised Register was searched (1 July 2011) using the codes for "toremifene", "fareston", "tamoxifen, "nolvadex, and "breast cancer". We also searched MEDLINE (via PubMed) (from inception to 1 July 2011), EMBASE (via Ovid) (from inception to 1 July 2011), The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 7, 2011), and the WHO International Clinical Trials Registry Platform search portal (1 July 2011). In addition, we screened the reference lists of relevant trials or reviews. SELECTION CRITERIA: Randomised controlled trials (RCTs) that compared the efficacy and safety, or both of TOR with TAM in women with advanced breast cancer. Trials that provided sufficient data on one of the following items: objective response rate (ORR), time to progression (TTP), overall survival (OS), and adverse events, were considered eligible for inclusion. DATA COLLECTION AND ANALYSIS: Studies were assessed for eligibility and quality. Two review authors independently extracted the following details: first author, publication year, country, years of follow-up, treatment arms, intention-to-treat (ITT) population size, menopausal status of patients, hormone receptor status, response criteria, efficacy and safety outcomes of TOR and TAM arms. Hazard ratios (HR) were derived for time-to-event outcomes, where possible, and response and adverse events were analysed as dichotomous variables. We used a fixed-effect model for meta-analysis unless there was significant between-study heterogeneity. MAIN RESULTS: A total of 2061 patients from seven RCTs were included for final analysis, with 1226 patients in the TOR group and 835 patients in the TAM group. The ORR for the TOR group was 25.8% (316/1226) whereas, the ORR for the TAM group was 26.9% (225/835). The pooled risk ratio (RR) suggested that the ORRs were not statistically different between the two groups (RR 1.02, 95% confidence interval (CI) 0.88 to 1.18, P = 0.83). The median TTP was 6.1 months for the TOR group and 5.8 months for the TAM group. The median OS was 27.8 months for the TOR group and 27.6 months for the TAM group. There were no significant differences in TTP and OS between the two therapeutic groups (for TTP: HR 1.08, 95% CI 0.94 to 1.24; for OS: HR 1.02, 95% CI 0.86 to 1.20). The frequencies of most adverse events were also similar in the two groups, while headache seemed to occur less in the TOR group than in the TAM group (RR 0.14, 95% CI 0.03 to 0.74, P = 0.02). There was no significant heterogeneity between studies in most of the above meta-analyses. Sensitivity analysis did not alter the results. AUTHORS' CONCLUSIONS: TOR and TAM are equally effective and the safety profile of the former is at least not worse than the latter in the first-line treatment of patients with advanced breast cancer. Thus, TOR may serve as a reasonable alternative to TAM when anti-oestrogens are applicable but TAM is not the preferred choice for some reason.

Lack of association between CYP17 MspA1 polymorphism and breast cancer risk: a meta-analysis of 22,090 cases and 28,498 controls.

Epidemiological studies have evaluated the association between CYP17 MspA1 polymorphism and breast cancer risk. However, the results remain conflicting rather than conclusive. To derive a more precise estimation of the relationship, we performed this meta-analysis. Systematic searches of the PubMed and Medline databases were performed. A total of 35 studies including 22,090 cases and 28,498 controls were identified. Genotype distributions of CYP17 in the controls of all studies were in agreement with Hardy-Weinberg equilibrium (HWE) except for three studies. When all 35 studies were pooled into the meta-analysis, there was no evidence for significant association between CYP17 MspA1 polymorphism and breast cancer risk (for A1/A2 vs. A1/A1: OR = 1.00, 95% CI = 0.96-1.04; for A2/A2 vs. A1/A1: OR = 1.03, 95% CI = 0.97-1.08; for dominant model: OR = 1.01, 95% CI = 0.97-1.05; for recessive model: OR = 1.03, 95% CI = 0.98-1.08). In the subgroup analyses by ethnicity, menopausal status and source of controls, no significant associations were found in all genetic models. When sensitivity analyses were performed by excluding HWE-violating studies, all the results were not materially altered. In summary, the meta-analysis strongly suggests that CYP17 MspA1 polymorphism is not associated with increased breast cancer risk.

microRNA-214 functions as a tumor suppressor in human colon cancer via the suppression of ADP-ribosylation factor-like protein 2.

microRNAs (miRNAs/miRs) are a conserved class of endogenous, short non-coding RNAs that post-transcriptionally regulate the expression of genes involved in diverse cellular processes. miR-214 has been reported to be associated with several cancers, including human colon cancer. However, the function of miR-214 in colon cancer development is poorly understood. In the current study, miR-214 was demonstrated to be downregulated in colon cancer tissues compared with healthy colon tissues. Functional studies showed that miR-214 overexpression results in the inhibition of cell viability, colony formation and proliferation, and the induction of cell apoptosis. ADP-ribosylation factor-like protein 2 (ARL2) is predicted to be a target candidate of miR-214. A luciferase reporter assay, western blot analysis and quantitative polymerase chain reaction were performed, which revealed that miR-214 negatively regulates ARL2 expression by targeting its 3' untranslated region directly. In conclusion, the results of the present study revealed that miR-214 suppresses colon cancer cell growth via the suppression of ARL2, and indicated that miR-214 may present a significant potential therapeutic target for colon cancer.

[Diagnostic value of combined detection of TPS, NSE and CEA in lung cancer].

OBJECTIVE: To study the diagnostic value of combined detection of 3 tumor markers, namely tissue polypeptide specific antigen (TPS), neuro-specific enolase (NSE) and carcinoembryonic antigen (CEA), in patients with lung cancer. METHODS: The serum levels of TPS, NSE and CEA were determined by enzyme-linked immumosorbent assay in 72 patients with lung cancer and 114 healthy adults. RESULTS: The levels of the 3 tumor markers in the patient group were significantly higher than those of the healthy control group (P<0.001). The sensitivity of TPS for lung cancer detection was 84.7% with specificity of 89.4%, which were 54.1% and 91.2% respectively for NSE, and 45.8% and 91.4% respectively for CEA. The combined detection of the 3 tumor markers for lung cancer diagnosis had a sensitivity of 100%. CONCLUSIONS: TPS, NSE and CEA employed separately are helpful in the diagnosis of lung cancer, and their combined detection may significantly improve the sensitivity for lung cancer detection, due to the obvious complementarity of the 3 markers.

[Clinical study of serum tissue polypeptide-specific antigen in breast cancer].

OBJECTIVE: To investigate the expression of serum tissue polypeptide-specific antigen (TPS) in breast cancer patients and its clinical value in such cases. METHODS: Altogether 160 subjects (90 patients with breast cancer, 40 with benign breast lesions, and 30 healthy subjects) were enrolled in this study. The serum TPS and CA153 levels were measured by ELISA in all the subjects. RESULTS: The levels and positivity rate of serum TPS and CA153 in breast cancer group were significantly higher than those in the normal subjects group and benign lesion group (P<0.01), and became even higher as the malignancy progressed. High serum TPS level was detected in the cancer patients in stage I. Serum TPS level was the most sensitive to bone metastasis of the malignancy, but its highest levels occurred in cases of lymphoid node metastasis (P<0.05). In patients who responded favorably to the treatment, serum TPS and CA153 levels were significantly reduced (P<0.05), but the reduction in TPS levels tended to be more obvious (P<0.05). CONCLUSION: Serum TPS can be used as a very useful and sensitive tumor marker in the diagnosis of breast cancer, especially in case of bone metastasis, and may be of great value in clinical decision-making and assessment of therapeutic effect.

[Gefitinib enhances the radiosensitivity of nasopharyngeal carcinoma cell line CNE2 in vitro].

OBJECTIVE: To study the radiosensitizing effect of gefitinib on nasopharyngeal carcinoma cell line CNE2 in vitro. METHODS: Nasopharyngeal carcinoma cell line CNE2 was cultured in RP2MI 1640. MTT assay was performed to evaluate the cell proliferation changes in response to gefitinib treatment and the radiosensitizing effect of gefitinib. The cell survival curves and sensitive enhancement ratio (SERs) were obtained with a clonogenic assay. Flow cytometry analysis was applied to detect the cell cycle changes and cell apoptosis. RESULTS: MTT assay showed that cells exposed to gefitinib and radiation had a significantly lower survival ratio compared to the cells with radiation exposure only (0.582∓0.012 vs 0.398∓0.016, P=0.002), with a SER of 1.535∓0.134. The S phase cell percentage was significantly decreased and G(2)-M phase cells increased in gefitinib plus radiation group (P=0.000), suggesting a synergistic effect of gefitinib and radiation. CONCLUSION: Gefitinib can enhance the radiosensitivity of nasopharyngeal carcinoma CNE2 cells in vitro possibly by inhibiting cell proliferation, inducing cell apoptosis, and causing changes in the cell cycle distribution.

[Inhibitory effect of ZD6474 combined with adriamycin on MCF-7 human breast cancer cells in vitro].

OBJECTIVE: To investigate the killing effect of ZD6474 combined with adriamycin (ADM) on MCF-7 human breast cancer cells. METHODS: The inhibitory effects of ZD6474 and ADM alone and in combination on the proliferation of MCF-7 cells were assessed by MTT assay. The cell cycle and cell apoptosis were detected by flow cytometry. RESULTS: ZD6474 and ADM both significantly inhibited the proliferation of MCF-7 cells, showing a synergistic effect of their reactions in combined use (P<0.05). ZD6474 or ADM alone caused cell cycle arrest at G0/G1 and S phases, respectively. Combined use of the two drugs resulted in significant reduction of the M-phase cell percentage and cell cycle arrest at G0/G1 and S phases. The coadministration of the drugs significantly increased the apoptosis rate of the cells as compared with ZD6474 or ADM treatment alone (P<0.05). CONCLUSIONS: ZD6474 and ADM show a synergistic effect in inhibiting the proliferation and inducing apoptosis of MCF-7 cells.

[Preliminary study of XELOX regimen as the first-line chemotherapy in advanced or recurrent gastric cancer].

OBJECTIVE: To evaluate the efficacy and toxicity of the combined therapy with oxaliplatin and capecitabine (XELOX) in patients with advanced or recurrent gastric cancer. METHODS: Forty-one patients with previously untreated advanced or recurrent gastric cancer received intravenous infusion of oxaliplatin at the dose of 130 mg/m(2) on day 1 and oral administration of capecitabine at 1000 mg/m(2) twice a day on days 1-14. The chemotherapy was repeated every 2 weeks for a median of 4 cycles. RESULTS: Two of 41 patients achieved a complete response, and 15 had partial responses, with an overall response rate of 41.5%. Stable disease was observed in 11 patients and progressive disease in 9. The median time to progression and overall survival was 6.2 months and 11.8 months. All the 41 patients were evaluated for toxicity according to NCI criteria, 4 showed grade 3-4 neural toxicity, 4 had hematological toxicity and 3 had hand-foot syndrome. CONCLUSION: The XELOX regimen shows good efficacy with an acceptable toxicity profile in advanced or recurrent gastric cancer patient.

[Inhibitory effects of recombinant adenovirus carrying human endostatin gene on the growth of human pancreatic carcinoma xenograft in nude mice].

OBJECTIVE: To evaluate the inhibitory effect of recombinant adenovirus carrying human endostatin gene (Ad-endo) on the growth of human pancreatic carcinoma xenograft in nude mice. METHODS: The expression of endostatin in human pancreatic carcinoma Capan-2 cells was examined by RT-PCR after infection with Ad-endo. The supernatants of Capan-2 cells were collected after 48 h of infection with Ad-endo as the conditioned medium for human umbilical vein endothelial cells (HUVECs), whose proliferation in vitro was assayed. Capan-2 cell xenografts were established to determine the antitumoral effects of Ad-endo in vivo. The intratumoral microvessel density (MVD) was evaluated using CD31 staining. RESULTS: The expression of endostatin gene was detected by PT-PCR in infected Capan-2 cells. The conditioned medium from Ad-endo-infected cells significantly inhibited HUVEC proliferation (P<0.05). Ad-endo significantly suppressed the growth of Capan-2 tumor xenografts in nude mice (P<0.05), and the MVD decreased significantly in the treated tumor (P<0.05) as compared with that in the control group. CONCLUSION: Adenovirus carrying human endostatin gene produces inhibitory effects on the growth of human pancreatic carcinoma tumors in nude mice.