Predictive factors of gefitinib response and survival in Chinese patients with local advanced or metastatic non-small cell lung cancer / 中国肺癌杂志

<p><b>BACKGROUND</b>Gefitinib, a selective inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase, has been approved effective in local advanced or metastatic non-small cell lung cancer (NSCLC), with the equivalent response rate to that of chemotherapy in Asian patients. Asian ethnicity, gender, smoking history, adenocarcinoma histology were remarkably associated with gefitinib response and survival. However, predictive factors of gefitinib response and survival are still unclear in Asian population. In this study, we retrospectively reviewed the data of 153 Chinese NSCLC patients who received a single agent of gefitinib with the purpose of identifying the potential predictive factors of gefitinib response and survival.</p><p><b>METHODS</b>Tumor response, survival and the clinicopathologic factors of 153 NSCLC patients treated between November of 2003 and June of 2004 were collected retrospectively from the multicenter clinical trial in China. Pearson Chi-square test and Logistic regression test were performed respectively as univariate and multivariate analyses of gefitinib response. Overall survivals between groups with different predictive factors were compared by log-rank tests. Multivariate analysis was performed to identify factors that independently predict for survival.</p><p><b>RESULTS</b>A total of 153 patients were included in this analysis. Objective response rate was statistically significant higher in patients with younger age (≤65 years) and longer interval from diagnosis to gefitinib treatment (≥6 months) in multivariate analysis (P < 0.05). The median follow-up duration was 10.0 months (0.5-16.8). The median survival was 10.3 months (95% CI: 8.1-12.6) and 1-year survival was 44.1%. Significant independent predictive factors associated with longer survival in multivariate analysis were good performance status (score 0-1), controlled disease (CR+PR+SD) to most recent chemotherapy and controlled disease to gefitinib (P < 0.05).</p><p><b>CONCLUSIONS</b>Gefitinib is effective in local advanced or metastatic NSCLC patients who failed to chemotherapy in Chinese population. In Chinese NSCLC population, younger age (≤65 years) and longer interval from diagnosis to gefitinib treatment (≥6 months) were predictive factors in multivariate analysis for gefitinib response; good performance status (score 0-1), controlled disease to most recent chemotherapy and controlled disease to gefitinib were independent prognostic factors for survival.</p>

DC loaded with CPP-Id increase the efficiency of CTL proliferation and enhance its cytotoxicity in vitro / 中国癌症杂志

Background and purpose:Dendritic cells(DCs) possess specialized feature such as pathogen recognition,antigen capturing and processing machinery,and stimulating naive T lymphocyte to have antitumor ability that allow them to act like professional APCs.This paper is aimed to confirm the impacts on the proliferation and secretion of INF-? of tumor specific CTL and its cytotoxocity induced by DC loaded with different antigen.Methods:After the stimulation of DC loaded with different antigen,the proliferative rate of allolymphocytes was measured by MTT and the cytotoxocity of CTL was evaluated with LDH method.The INF-? secreted by activated T lymphocytes was detected by ELISPOT.Results:The DC loaded with CPP-Id(320%?15%) had significantly induce T lymphocyte proliferating when comparing with the induction by DC loaded with Id(57%?10%)(P

Apoptosis induced by DNA primase inhibitor 3,3'-diethyl-9-methylthia-carbocyanine iodide in human leukemia HL-60 cells / 药学学报

Aim To investigate apoptosis induced by 3,3'-diethyl-9-methylthia-carbocyanine iodide(DMTCCI) , an inhibitor of DNA primase found in our previous study, and the mechanism of DMTCCI in human myelogenous leukemia HL-60 cells. Methods HL-60 cells were cultured in RPMI-1640 medium and treated with different concentrations of DMTCCI. MTT assay was used to detect growth inhibition.Flow cytometry and DNA ladders were used to detect apoptosis. Western blotting was used to observe the expression of survivin, Bcl-xL, Bad, Bax, Bcl-2, caspase-9, caspase-3, caspase-6, PARP, DFF45 and lamin B protein. Caspase-3 activity was measured by ApoAlert Caspase-3 Assay Kit. Results DMTCCI inhibited proliferation of human leukemia HL-60 cells with IC50 value of 0. 24 μmol · L-1. The results of flow cytometry and DNA ladders showed that DMTCCI could induce apoptosis of HL-60 cells. The expression levels of protein survivin and Bcl-xL were down-regulated, Bad and Bax were up-regulated,while Bcl-2 protein had no change in response to DMTCCI treatment in HL-60 cells. Treatment of HL-60cells with DMTCCI induced the proteolytic cleavage of caspase-9, caspase-3, caspase-6, PARP, DFF45and lamin B protein. Caspase-3 activity apparently increased at 3 h and reached a peak at 12 h after exposure to 1 μmol · L-1 of DMTCCI in HL-60 cells. Conclusion DMTCCI inhibited proliferation and induced apoptosis of human leukemia HL-60 cells. Bcl-2 family proteins, survivin and caspases family proteins might playa role in the apoptosis process induced by DMTCCI.

Results of randomized, multicenter, double-blind phase III trial of rh-endostatin (YH-16) in treatment of advanced non-small cell lung cancer patients / 中国肺癌杂志

<p><b>BACKGROUND</b>Endostar™ (rh-endostatin, YH-16) is a new recombinant human endostatin developed by Medgenn Bioengineering Co. Ltd., Yantai, Shandong, P.R.China. Pre-clinical study indicated that YH-16 could inhibit tumor endothelial cell proliferation, angiogenesis and tumor growth. Phase I and phase II studies revealed that YH-16 was effective as single agent with good tolerance in clinical use.The current study was to compare the response rate , median ti me to progression (TTP) ,clinical benefit andsafety in patients with advanced non-small cell lung cancer ( NSCLC) , who were treated with YH-16 plus vi-norelbine and cisplatin (NP) or placebo plus NP.</p><p><b>METHODS</b>Four hundred and ninety-three histologically or cy-tologically confirmed stage IIIB and IV NSCLC patients , withlife expectancy > 3 months and ECOG perform-ance status 0-2 , were enrolledin a randomized ,double-blind ,placebo-controlled , multicenter trial ,either trialgroup : NP plus YH-16 (vinorelbine 25 mg/m² on day 1 and day 5 ,cisplatin 30mg/m² on days 2 to 4 , YH-167.5mg/m² on days 1 to 14) or control group : NP plus placebo (vinorelbine 25 mg/m² on day 1 and day 5 ,cis-platin 30 mg/m² on days 2 to 4 ,0.9% sodium-chloride 3 .75 ml on days 1 to 14) every 3 weeks for 2-6 cycles .The trial endpoints included response rate ,clinical benefit rate ,time to progression,quality of life and safety .</p><p><b>RESULTS</b>Of 486 assessable patients , overall response rate was 35.4% in trial group and 19.5% in controlgroup (P=0 .0003) . The median TTP was 6 .3 months and 3 .6 months for trial group and control group respectively (P < 0 .001) . The clinical benefit rate was 73 .3 %in trial group and 64.0% in control group (P=0 .035) .In untreated patients of trial group and control group ,the response rate was 40 .0% and 23.9%(P=0 .003) ,the clinical benefit rate was 76 .5 % and 65 .0 % (P=0 .023) ,the median TTP was 6 .6 and 3 .7months (P=0 .0000) ,respectively .In pretreated patients of trial group and control group ,the response ratewas 23.9% and 8.5%(P=0 .034) ,the clinical benefit rate was 65.2% and 61.7%(P=0 .68) ,the median TTP was 5 .7 and 3 .2 months (P=0 .0002) ,respectively . The relief rate of clinical symptoms in trial groupwas higher than that of those in control group ,but no significance existed (P > 0 .05) . The score of quality oflife in trial group was significantly higher than that in control group (P=0 .0155) after treatment . There were no significant differences in incidence of hematologic and non-hematologic toxicity , moderate and severe sideeffects betweentrial group and control group .</p><p><b>CONCLUSIONS</b>The addition of YH-16 to NP regimen results in significantly and clinically meaningful improvement in response rate , median time to tumor progression,and clinical benefit rate compared with NP alone in advanced NSCLC patients . YH-16 in combination with chemotherapy shows a synergic activity and a favorable toxic profile in advanced cancer patients .</p>

Expression of fas and P53 protein in resected non-small cell lung cancer and its prognostic significance / 中国肺癌杂志

<p><b>BACKGROUND</b>To study the expressions and its clinical significances of fas and P53 protein in human non-small cell lung cancer (NSCLC) after complete surgical resection.</p><p><b>METHODS</b>Immunohistochemical stain of fas and P53 was performed on paraffin-embedded sections from 269 NSCLC patients who underwent surgery and were followed up for 1.1 to 122.2 (median, 48.4) months postoperatively. Differences in survival rates and clinical characteristics were evaluated by SPSS10.0 statistical software packet.</p><p><b>RESULTS</b>The rate of fas and P53 expression in NSCLC cancer tissue was 43.1% and 49.4% respectively. Fas expressions were seen more frequently in female patients (59.3% vs 39.1%, P < 0.01). Univariate analysis showed that fas expression was a good factor for predicting prognosis. The 5-year survival rate of the patients whose tumors had positive fas expression was significantly better than those individuals whose tumors had negative fas expression (51.4% vs 42.4%, P=0.02), especially in patients in stage I and IIIA . The expression of P53 had no significant influence on the prognosis of these 269 NSCLC patients. Combined analysis of fas and P53 expression in NSCLC cancer tissues showed significant prognostic influence (P=0.01). The 5-year survival were 40.1% (fas+ and P53-), 45.4% (both positive or both negative) and 57.2% (fas- and P53+), respectively. COX multivariate analysis showed that reduced fas expression in 269 NSCLC is an independent risk factor, especially in stage IIIA NSCLC.</p><p><b>CONCLUSIONS</b>Fas and P53 protein are indicators of NSCLC biological behavior. Reduced fas expression in NSCLC is an independent risk factor for early stage patients. Analysis of apoptosis related proteins expression in tumors might be helpful to predict the prognosis of patients with NSCLC.</p>

Amifostin in protection of kidney from cisplatinum injury / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate Amifostin's effect on protecting kidney from cisplatinum (DDP) injury and its adverse reactions and safety.</p><p><b>METHODS</b>193 Patients were divided into two groups randomly: 102 in group A (treatment group) and 91 in group B (control group). Indexes such as blood routine, blood calcium, liver function, blood urea nitrogen (BUN), cretinine (C), and urinary N-acetyl-beta-D-glucosaminidase (NAG)/C and micro-albumin (MAB/C) were monitored at different intervals before or after treatment.</p><p><b>RESULTS</b>In the two courses of treatment in both groups, the deviation (D) values of MAB/C before treatment and on D2 in group A were lower than those in grop B (P < 0.05), so were those before treatment and on D4, D6, D10 and D14 (P < 0.01). The D-values of NAG/C before treatment and on D4, D6, D10 and D14 in the first course of group A were obviously lower than those on the corresponding days in group B (P < 0.01), so were those before treatment and on D2, D4, D6, D10 and D14 in the second course (P < 0.01).</p><p><b>CONCLUSION</b>The reduction of MAB/C and NAG/C by Amifostin in group A demonstrates that: Amifostin is able to effectively protect the renal function, regardless of the type of tumor. In contrast with group B, Amifostin in group A shows no protection for tumor in lung cancer and ovarian cancer. The main side effects of Amifostin are mild hypotension, nausea, vomiting and hypocalcemia in some patients.</p>

Capecitabine (xeloda) in the treatment of relapsed and metastatic breast cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the response rate and adverse reactions of xeloda, an analogue of 5-fluorouracil, in the treatment of relapsed and metastatic breast cancer.</p><p><b>METHODS</b>Twenty-two breast cancer patients who had recurrent and metastatic measurable foci were treated from Dec. 1999 to Feb. 2000. Xeloda was given, as a single drug, at a dose of or 2,510 mg/m2/d, bid, for two weeks followed by one week rest as one cycle, at least for one cycle in each patient.</p><p><b>RESULTS</b>Among these 22 patients, there was no complete response. Rates of partial response 8(36.4%), stable disease 10(45.5%), progressive disease 4(18.2%), and clinical benefit response (CR + PR + SD) 18(81.8%). The response rate in patients who had failed in previous chemotherapy of taxanes and/or anthracycline was 30.0%-33.3%. The common adverse reactions were hand-foot syndrome, skin pigmentation, nausea, vomiting, anorexia and fatigue. Mild-moderate anemia and leukopenia were observed in 36.4% of patients. Stomatitis, dizziness, diarrhea and chest distress were present in some. One patient developed degree IV myelosuppression. Total bilirubin and alanine transaminase (ALAT) mild elevation occurred in a few patients.</p><p><b>CONCLUSION</b>Xeloda is an effective drug in the treatment of patients with relapsed and metastatic breast cancer, especially for those who have failed in chemotherapy with taxanes and/or anthracycline. Xeloda is well tolerated but has mild adverse reactions.</p>

HER-2/neu gene amplification and expression in nasopharyngeal carcinoma and their clinical significance / 中国癌症杂志

Purpose:To study HER-2/neu gene amplification and expression in nasopharyngeal carcinoma (NPC) and their clinical significance.Methods:HER-2/neu gene amplification and expression in NPC tissues were detected with fluorescence in situ hybridization (FISH,Vysis PathVysion TM kit) and reverse transcription polymerase chain reaction (RT-PCR) and immounhistochemistry (IHC,DAKO Herceptin Test TM kit).Results:No HER-2/neu gene amplification but gene overexpression was detected in NPC. HER-2/neu overexpression was caused by mRNA overexpression.Conclusions:HER-2/neu gene has not been amplified,but overexpressed,thus HER-2/neu gene overexpression did not show prognostic significance in NPC.

Phase Ⅱ clinical study of intratumoral H101,an E1B deleted adenovirus,in patients with cancer / 中国癌症杂志

Purpose:To evaluate the efficacy and toxicity o f intratumoral H101, an E1B deleted oncolytic adenovires. Methods :A total of 53 patients with malignant tumors from multiple centers were treated with H101, 5?10 11 viral particle (VP) per day for 5 consecutive days ever y three weeks. The efficacy and toxicity were evaluated. Results :Among 49 evaluable cases, complete response 2, partial response 9, minimal respo nse 8, stable disease 19, progressive disease 11, overall response rate was 22.4 %. In the 56 ITT population the response rate was 19.6%, including 2 CR and 9 PR . The rate of clinical benefit response (CR+PR+MR+SD) was 77.6% (38/49). Main si de effects were injection site pain (57.4%) and fever (35.2%). No serious advers e events developed. Conclusions:The study showed that genetical ly E1B-deleted adenovirus (H101) showed some efficacy in some refractory malign ant tumors, and was well tolerated.