BackgroundAdjuvant chemotherapy (AC) improves survival among patients with operable breast cancer. However, the effect of delay in AC initiation on survival is unclear. We performed a systematic review and meta-analysis to determine the relationship between time to AC and survival outcomes.MethodsPubMed, EMBASE, Cochrane Database of Systematic Reviews, and Web-of-Science databases (between January-1 1978 and January-29, 2013) were searched for eligible studies. Hazard ratios (HRs) for overall survival (OS) and disease-free survival (DFS) from each study were converted to a regression coefficient (β) corresponding to a continuous representation per 4-week delay of AC. Most used regimens of chemotherapy in included studies were CMF (cyclophosphamide, methotrexate, and fluorouracil) or anthracycline-based. Individual adjusted β were combined using a fixed-effects or random-effects model depending on heterogeneity.ResultsWe included 7 eligible studies with 9 independent analytical groups involving 34,097 patients, 1 prospective observational study, 2 secondary analyses in randomized trials (4 analytical groups), and 4 hospital-/population-based retrospective study. The overall meta-analysis demonstrated that a 4-week increase in time to AC was associated with a significant decrease in both OS (HR = 1.15; 95% confidence interval [CI], 1.03-1.28; random-effects model) and DFS (HR = 1.16; 95% CI, 1.01-1.33; fixed-effects model). One study caused a significant between-study heterogeneity for OS (P < 0.001; I2 = 75.4%); after excluding that single study, there was no heterogeneity (P = 0.257; I2 = 23.6%) and the HR was more significant (HR = 1.17; 95% CI, 1.12-1.22; fixed-effects model). Each single study did not fundamentally influence the positive outcome and no evidence of publication bias was observed in OS.ConclusionsLonger time to AC is probably associated with worse survival in breast cancer patients.
Interspecies nuclear transfer is an invaluable tool for studying nucleus-cytoplasm interactions; and at the same time, it provides a possible alternative to clone animals whose oocytes are difficult to obtain. In the present study, we investigated the possibility of cloning cat embryos using rabbit oocytes, and compared the developmental capacity; the timing of embryogenesis of the cat-rabbit cloned embryos with that of the cat-cat or the rabbit-rabbit cloned embryos. When cultured in M199, the rate of blastocyst formation of the cat-rabbit embryos was 6.9%, which was not significantly different than that of the cat-cat embryos (10.5%). However, the rate of blastocyst formation of rabbit-rabbit embryos (22.9%) was significantly greater than that of both the cat-rabbit and the cat-cat embryos (P < 0.05). The timing of the first three cleavages for the cat-rabbit embryos was similar to that of the rabbit-rabbit embryos, but significantly faster than that of the cat-cat embryos (P < 0.05), while the time to form blastocysts was similar to that of cat-cat embryos, but significantly slower than that of the rabbit-rabbit embryos (P < 0.05). Both M199 and SOF medium were evaluated for culturing cat-rabbit embryos; the rate of blastocyst formation in SOF (14.5%) was significantly greater than that in M199 (6.9%) (P < 0.05). These results demonstrate that: (1) the cat-rabbit embryos possess equal developmental capacity as cat-cat embryos; (2) the timing of the first three cleavages for the cat-rabbit embryos is recipient-specific, while the time to form blastocysts is donor nucleus-specific; and (3) SOF medium may be beneficial to overcome the morula-to-blastocyst block for cat-rabbit cloned embryos.
Antibacterial peptide CM4 (ABP-CM4) is a small cationic peptide with broad-spectrum activities against bacteria, fungi, and tumor cells, which may possibly be used as an antimicrobial agent. We report here the application of small ubiquitin-related modifier (SUMO) fusion technology to the expression and purification of cationic antibacterial peptide ABP-CM4. The fusion protein expressed in a soluble form was purified to a purity of 90% by Ni-IDA chromatography and 112 mg protein of interest was obtained per liter of fermentation culture. After the SUMO-CM4 fusion protein was cleaved by the SUMO protease at 30 degrees C for 1 h, the cleaved sample was re-applied to a Ni-IDA. Finally, about 24 mg recombinant CM4 was obtained from 1 l fermentation culture with no less than 96% purity and the recombinant CM4 had similar antimicrobial properties to the synthetic CM4. Thus, the SUMO-mediated peptide expression and purification system potentially could be employed for the production of recombinant cytotoxic peptides.
BackgroundWe aimed to evaluate the prognostic value of the lymph node ratio (LNR) in patients with axillary lymph node-positive triple-negative breast cancer (TNBC).MethodsThe prognostic efficacy was investigated in the first cohort from the Surveillance, Epidemiology, and End Results (SEER) dataset (n=4114) and was further validated in an independent cohort from Fudan University Shanghai Cancer Center (n=417). Patients were classified into low-, medium- and high-risk LNR groups.ResultsMultivariate analysis revealed that the LNR was an independent predictor of overall survival (hazard ratio (HR) for high-risk LNR: 3.24; 95% confidence interval (CI): 2.56 to 4.09) and breast cancer-specific survival (HR for high-risk LNR: 3.57; 95% CI: 2.76 to 4.62) in the SEER population and also for disease-free survival (HR for high-risk LNR: 4.29; 95% CI: 2.24-8.21) in the validation population. Subgroup analysis revealed that patient classification according to the LNR could discriminate among groups of patients with different survival rates based on pathological nodal (pN) staging.ConclusionThe LNR shows potential for use as an additional prognostic factor for TNBC patients with positive lymph node involvement. Considering the heterogeneity of TNBC, use of the LNR might allow for optimization of the pN staging system and should be considered when making treatment decisions.
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