ABSTRACT
<p><b>OBJECTIVE</b>To investigate the clinicopathological characteristics and prognosis in breast cancer with brain metastasis (BCBM).</p><p><b>METHODS</b>The clinical data of 137 BCBM from June 2002 to June 2008 was reviewed and analyzed. Their molecular subtypes were categorized based on detection of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER-2) expression. The focal area included 35 cases of triple-negative breast cancer (TNBC), 38 cases of HR (ER and PR) (-)/HER-2(+), 40 cases of HR(+)/HER-2(-), 24 cases of HR(+)/HER-2(+). The clinical characteristics and the outcome in patients with influence were analyzed.</p><p><b>RESULTS</b>In 137 BCBM, the median overal survival after brain metastasis was 6.5 month. The median survivals of TNBC, HR(-)/HER-2(+), HR(+)/HER-2(-) and HR(+)/HER-2(+) were 5.0, 5.5, 10.0 and 9.5 months, respectively. The median survivals after brain metastasis of the breast cancer patients who received the combination therapy of whole brain radiation therapy (WBRT) and neurosurgery and/or stereotactic radiosurgery, received WBRT but not combination therapy and didn't receive WBRT were 15.0, 9.5 and 4.0 months, respectively. In univariate survival analysis, substyle, number of brain metastasis, brain metastasis as initial recurrence or not, brain-only metastases or not, the combination therapy status after brain metastasis were obviously correlated with the prognosis (χ(2) = 6.891 to 29.414, P < 0.05). Substyle (RR = 1.234, 95%CI: 1.057 to 1.440) and the combination therapy status after brain metastasis (RR = 1.838, 95%CI: 1.389 to 2.431) were independent prognostic factor in multivariable analysis (P < 0.05).</p><p><b>CONCLUSIONS</b>TNBC confers a high risk of death after brain metastases. Systemic treatment via combined modalities are helpful for breast cancer patients, even after the detection of brain metastases.</p>
Subject(s)
Adult , Aged , Female , Humans , Middle Aged , Brain , Pathology , Brain Neoplasms , Therapeutics , Breast Neoplasms , Pathology , Therapeutics , Combined Modality Therapy , Prognosis , Retrospective Studies , Survival Analysis , Triple Negative Breast Neoplasms , Pathology , TherapeuticsABSTRACT
Our previous work has indicated that mycelium growth and exopolysaccharide accumulation in submerged fermentation by Pholiota squarrosa (Pers. ex Fr.) Quel. AS 5.245 are strongly affected by many internal and external factors, including medium constituents and fermentation conditions. In this study, we use an effective two-phase statistical approach to enhance exopolysaccharide production. In the first phase, Plackett-Burman design was undertaken to evaluate the effects of the twenty factors, i.e., glucose, fructose, maltose, yeast extract, tryptone, K2HPO4, KH2PO4, (NH4)2SO4, NaNO3, FeSO4, MgSO4, MnCl2, ZnCl2, FeCl3, CuSO4.5H2O, vitamin B1, initial pH, the temperature, the medium volume and the duration, to the fermentation. By regression analysis, yeast extract, tryptone, fructose, MgSO4, MnCl2, initial pH and temperature were found to be important for exopolysaccharide production, while glucose, maltose, NaNO3, ZnCl2, vitamin B1, the duration and the volume are important to the mycelium biomass. In the second phase of the optimization process, a response surface methodology (RSM) was used to optimize the above critical internal factors, and to find out the optimal concentration levels and the relationships between these factors. Based on the results of the first phase, a five-level six-factor (yeast extract, fructose, MgSO4, maltose, ZnCl2 and initial pH) central composite rotatable design (CCRD) was employed. By solving the quadratic regression model equation using appropriate statistic methods, the optimal concentrations for obtaining 876.32 microg exopolysaccharide per milliliter of fermentation liquor were calculated as: 6.0g/L yeast extract, 11.5g/L fructose, 0.5g/L MgSO4, 9.6g/L maltose, 38.6mg/L ZnCl2 and with the initial pH 5.3. The experimental data under various conditions have validated the theoretical values.
Subject(s)
Culture Media , Fermentation , Fructose , Metabolism , Hydrogen-Ion Concentration , Maltose , Metabolism , Pholiota , Metabolism , Polysaccharides , TemperatureABSTRACT
Response surface methodology (RSM) based on a three-level three-factor Box-Behnken design of experiments was used to optimize the extracellular polysaccharide content and the mycelium biomass by submerged cultivation using Pholiota squarrosa AS 5.245. The critical factors selected for the investigation were temperature, time of cultivation and volume of medium, based on the results of our previous Plackett-Burman design. The objectives of this present work were to locate optimum levels of these process parameters, and to find out interactions among them for enhancement of the yield of extracellular polysaccharide and mycelium biomass. By solving the regression equation and also by analyzing the response surface contour plots, the optimal process conditions were determined: under conditions of temperature, 28.07℃; cultivation time, 8.79 d and volume of medium, 68.51 mL, the prediction of extracellular polysaccharide content (EPC) by Pholiota squarrosa AS 5.245 was 1062.69 ?g per milliliter of fermentation liquor. While cultivation temperature, time and volume of medium were 27.60℃, 9.42 d and 54.20 mL respectively, the mycelium biomass expressed as dry cell weight (DCW) was 11.32 mg?mL -1. In order to simultaneously obtain the maximum yield of EPC and DCW, the above conditions would be located at 27.62℃, 9.19 d and 64.10 mL. In these conditions, the maximum predicted yield of EPC and DCW were found to be 1050.64 ?g?mL -1 and 11.10 mg?mL -1, respectively. These predicted values were also verified by validation experiment.