K-ras gene is one of oncogenes,which promotes cells growth and differentiation.Ras protein loses the activity of GTP enzyme because of K-ras mutations,and that may cause abnormal growth,differentiation of cells and promote the occurrence of tumor.Patients with colorectal carcinoma that carry mutations in K-ras gene do not benefit from the administration of anti-epidermal growth factor receptor (EGFR) polyclonal antibodies.Different solid tumors of colorectal carcinoma have different K-ras mutation rates.Different genotypes of K-ras gene (wild-type or K-ras mutant type) affect significantly on treatment options and prognosis.The efficacy of mutant type patients with anti-EGFR antibodies is poor,and the therapeutic effects of 5-FU and FOLFOX are still unclear.

A methodology named immunoscorehas been proposed in recent years.It has been demonstrated to be a prognostic factor superior to the Union for International Cancer Control-American Joint Committee on Cancer (UICC-AJCC)TNMclassification.Over the past few years,it has gained a forefront posi-tion in colorectal cancer.It has the advantages of simple operation,low cost and high accuracy,and it is nee-ded for individual therapy.However,it still has its limitations.

Purpose:To study the response rate and adverse reactions of gemcitabine and cisplatin in the treatment of advanced liver cancer and the disease related symptoms improvement(DRSI). Methods:16 patients of advanced liver cancer were treated from Dec. 1999 to Dec. 2001.Gemcitabine was used intravenously by infusion for 30 min with the dose from 1 000 mg/m 2 to 1 250 mg/m 2 on day 1,8,cisplatin was infused intravenously with a dose of 25 mg/m 2 on day 1,2,3.Twenty one days were counted as one cycle. After 2 cycles of the treatment the response rate and adverse reaction and clinical symptoms were evaluated. Results:Among these 16 patients,there was no complete response,PR 4(25%),MR 6(37.5%),SD 4(25%),PD 2(12.5%),and clinical benefit response(CR+PR+MR+SD)14(87.5%). DRSI could be observed in 31.3%(5/16) for 1 cycle and 68.8%(11/16) for 2 cycles.The main adverse reactions were hematologic toxicity(grade 3/4),which included leucopenia 15.4%(6/39),anemia 12.8%(5/39),thrombocytopenia 25.6%(10/39),and nonhematologic toxicity was mild.Conclusions:Combination of gemcitabine with cisplatin was an effective and new chemotherapy for advanced liver cancer,it has high DRSI and mild adverse reactions.

Objective To explore the effect of ectopic overexpression of Smac/DIABLO on the proliferation of pancreatic cancer cell line SW1990,and the sensitization to TRAIL and Gemcitabine induced apoptosis.Methods The Smac/DIABLO gene was transfected into the pancreatic cancer cell line SW1990 with the participation of Lipofectamine 2000 (SW1990/Smac).The cell line transfected with empty vector served as controls (SW1990/neo).The SW1990/neo and SW1990/Smac cells were assigned into the following treatment groups:TRAIL group,Gemcitabine group,TRAIL plus Gemcitabine group,and the control group.The SW1990 cells were treated with TRAIL and Gemcitabine in different concentrations and time.The cell growth inhibition rate (CGIR) was detected by MTT,the rate of apoptosis was measured by flow eytometry,the apoptosis morphous was observed by Heochst 33342 staining.The expressions of apoptosis-associated proteins such as Smas/DIABLO,XIAP,cytochrome C and caspase-3 were detected by Western blot.Results The cell growth of SW1990/Smac was significantly lower than growth of SW1990/ neo.The concentration of TRAIL were 200,500,1000 and 2500 ng/ml respectively.After 24 hours,the CGIR of SW1990/neo and SW1990/Smac were 11.11％,46.03％,67.08％,76.19％ and 22.11％,42.67％,56.63％,67.6％ respectively (P ＜ 0.05).The concentration of Gemcitabine were 10,20,40 and 60 μmol/L respectively.After 24 hours,the CGIR of SW1990/neo and SW1990/Smac were 15.2％,34.6％,55.16％,76.4％ and 22.65％,36.85％,55.11％,79.99％ respectively (P＜0.05).The cells of SW1990/neo and SW1990/Smac were treated by TRAIL(500 ng/ml),Gemcitabine (20 μmol/L) and combination group.The apoptosis rate were 5.64％,15.30％,27.27％ and 20.37％,23.27％,67.30％ (P ＜ 0.05) respectively.In combination group,the expressions of activators of caspase such as Smas/DIABLO,cytochrome C and caspase-3 increased significantly,while the expressions of inhibitor of apoptosis protein XIAP decreased.Conclusions Ectopic expression of Smac/DIABLO could induce the apoptosis of SW1990 cell,inhibit the cell proliferation,and enhence the sensitivity of SW1990 cell to TRAIL and Gemcitabine.The mechanism of apoptosis sensitization effect by Smac/DIABLO was associated with significant up-regulation of Smac/DIABLO,cytochrome C,down-regulation of XIAP,and the activation of caspase-3.

Antibodies, Monoclonal, Murine-Derived ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Humans ; Lymphoma, Follicular ; drug therapy ; Rituximab

OBJECTIVEA prospective, multicenter and non-interventional prospective study was conducted to evaluate the clinical features of rituximab combined with chemotherapy (R-Chemo) as first-line treatment on newly diagnosed Chinese patients with diffuse large B-cell lymphoma (DLBCL).

METHODSThis was a single arm, prospective, observational multicenter and phase IV clinical trial for 279 patients, who were newly diagnosed as CD20-positive DLBCL from 24 medical centers in China 2011 and 2012, no special exclusion criteria were used. All patients received rituximab based R-Chemo regimes, such as R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisolone) and other regimes as the first-line treatment. The treatment strategies were determined by physicians and patients without detailed description for treatment course, dose, interval time and examination. Clinical response and safety of all patients were investigated in 120 days after completion of last dose of rituximab.

RESULTSOf 279 patients, 258 with stage I-IV who received at least 1 cycle of rituximab treatment and completed at least one time of tumor assessment were enrolled into intention-to-treat analysis, including 148 male and 110 female. The median age of all patients was 57.2(12.8-88.4) years. ECOG performance statuses of 0 or 1 were observed in 91.1% of patients, international prognostic index levels in the low-risk and low-middle-risk groups in 76.4% of patients, the tumor diameters smaller than 7.5 cm in 69.0% of patients. All patients received 6 median cycles of R-Chemo treatment every 24.4 days. R-CHOP treatment was shown to improve the clinical response with overall response rates of 94.2%. Common adverse events included anemia, marrow failure, leukopenia, thrombocytopenia, digestive diseases, infection and liver toxicity. All adverse events are manageable.

CONCLUSIONNon-interventional clinical trial of R-Chemo remains the standard first-line treatment for newly diagnosed patients with DLBCL in real clinical practice, which is consistent with international treatment recommendations for DLBCL patients. R-Chemo can provide the clinical evidence and benefit as the first-line standard treatment for Chinese patients with DLBCL.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antibodies, Monoclonal, Murine-Derived ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Child ; Female ; Humans ; Lymphoma, Large B-Cell, Diffuse ; drug therapy ; Male ; Middle Aged ; Prospective Studies ; Rituximab ; Treatment Outcome