Aim-The aim of this study was to determine the safety and the efficacy of a gemcitabine/oxaliplatin combination (GEMOX) as first line therapy in patients with metastatic or unresectable locally-advanced pancreatic can...Aim-The aim of this study was to determine the safety and the efficacy of a gemcitabine/oxaliplatin combination (GEMOX) as first line therapy in patients with metastatic or unresectable locally-advanced pancreatic cancer. Patients and methods-Patients received gemcitabine 1000 mg/m2 as a 10 mg/m2/min infusion on day 1 followed on day 2 by oxaliplatin 100 mg/m2 as a 2 hour infusion, each cycle being given every 2 weeks. All patients had measurable disease and histological diagnosis before inclusion. Patients were treated until progression or for 12 cycles in the absence of progression. Tumor lesions were assessed by computed tomography scan every 4 cycles. Results-Between January 2001 and January 2003, 32 patients were eligible for the study. The objective response rate (OR) was 28.1%with a 12.5%complete response rate (CR). Median progression-free survival and median overall survival were 7 and 9 months, respectively. Median overall survival for patients with metastatic disease and locally-advanced disease were 7 and 25 months, respectively (P < 0.0007). Eleven patients were alive at 1 year (34.4%), six at 2 years (18.8%) and two at 3 years (6%). Fourteen (43.8%) of 32 patients experienced a clinical benefit response. Conclusion-These results support the safety, the antitumor activity and the possibility of durable responses of the GEMOX regimen in patientswith locally-advanced disease.展开更多
Mutations in activation-induced cytidine deaminase can cause an autosomal rec essive form of hyper-IgM syndrome. We have examined a Tunisian family composed of six members: two healthy parents, their two healthy daugh...Mutations in activation-induced cytidine deaminase can cause an autosomal rec essive form of hyper-IgM syndrome. We have examined a Tunisian family composed of six members: two healthy parents, their two healthy daughters and two affecte d sons. We found a homozygous transversion G to T in the two sons while heterozy gosity for the mutation was found in all other family members. This alteration i s localised in intron 2 at the +1 position resulting in defective splicing. Use of various intronic cryptic splice-sites led to expression of various aberrant mRNA species. Conclusion: This is a novel mutation found in the gene encoding f or activation-induced cytidine deaminase in a Tunisian family with hyper-IgM t ype 2 syndrome. This alteration leads to the use of two cryptic splicing sites c ausing the formation of two different mRNA species.展开更多
Objectives.:Platinum resistance is a significant problem in patients with ovarian cancer. The aim of this phase II study was to define the response rates,the progression-free survival and the toxicity profile of the c...Objectives.:Platinum resistance is a significant problem in patients with ovarian cancer. The aim of this phase II study was to define the response rates,the progression-free survival and the toxicity profile of the combination of PEG liposomal doxorubicin (L-DXR) and gemcitabine (GEM). Material and methods.:Thirty one patients with histologically confirmed platinum-refractory or-resistant epithelial ovarian cancer were scheduled to receive 6 cycles of L-DXR 30 mg/m2 on day 1 as well as GEM 650 mg/m2 on days 1 and 8 every 28 days. Results.:The median number of chemotherapy cycles given was 4. The mean dose intensity for L-DXR and GEM on day 1 was 96%and 97%,respectively. The mean dose intensity for GEM on day 8 was 93%. The overall response rate was 33%(10 of 30 evaluable patients; 20%complete responses). The median progression-free survival was 3.8 months,and the median overall survival was 15.8 months,respectively. Toxicity was acceptable. One quarter of patients developed grade 3 or 4 neutropenia,but none developed febrile neutropenia. Palmoplantar erythrodysesthesia (PPE) grades 2 and 3 occurred in 13%and 3%only,respectively,and no grade 4 PPE was observed. Grades 1 to 3 stomatitis was found in 58%of patients (10%grade 3). Conclusion.:The combination of L-DXR and GEM is an active and acceptably tolerated option in the treatment of patients with platinum-resistant and-refractory ovarian cancer. Dose reductions seem advisable in the case of ≥grade 2 stomatitis and/or PPE ≥grade 2.展开更多
Background.:To determine the pathologic complete response rate of advanced ovarian cancer to weekly paclitaxel plus gemcitabine and carboplatin with filgrastim,and assess the longitudinal impact of this regimen on qua...Background.:To determine the pathologic complete response rate of advanced ovarian cancer to weekly paclitaxel plus gemcitabine and carboplatin with filgrastim,and assess the longitudinal impact of this regimen on quality-of-life and cognitive functioning. Methods.:Fourteen patients with advanced ovarian,peritoneal,or fallopian tube cancer were treated in the phase I portion of the study. Initial doses were paclitaxel:60 mg/m2 days 1,8,and 15; gemcitabine:800 mg/m2 days 1 and 8; and carboplatin:area under the curve (AUC) 5 day 1,every 21 days for 6 cycles with filgrastim. Twenty-seven patients were treated at the phase II dose. Pathologic response was assessed by second-look laparoscopy in patients with complete response. Patients completed longitudinal assess- ments of quality-of-life and cognitive functioning. Results.:Maximally tolerated doses were paclitaxel:80 mg/m2 days 1 and 8; gemcitabine:800 mg/m2 days 1 and 8; and carboplatin:AUC 5 day 1,every 21 days. Forty-eight percent of patients (13/27) experienced at least 1 grade 3 nonhematologic toxicity. Fifty percent (95%confidence interval CI ,31-69%) of assessable patients achieved pathologic complete response. Median progression-free survival was 27.3 months (95%CI,17.7 months to not reached),and overall survival 43.6 months (95%CI,42 months to not reached). Cognitive functioning did not decline during or after chemotherapy. More highly educated women reported a perceived decline in concentration and memory while on chemotherapy. Quality-of-life scores were maintained during therapy. Conclusions.:Fifty percent of patients with advanced stage ovarian cancer achieved pathologic complete response to weekly paclitaxel plus gemcitabine and carboplatin. Cognitive functioning did not decline by objective measures,although highly educated women reported subjective impairment.展开更多
文摘目的:寻求一种快速稳定的方法从人外周血中诱导培养出成熟的树突细胞(DC)。方法:用密度梯度离心法从正常人外周血中分离出单个核细胞(PBMC),再用贴壁法获取单核细胞,在0 h加入粒细胞-巨噬细胞集落刺激因子(GM-CSF)、白细胞介素-4(IL-4),随后分四组继续培养:第一组在24 h加入多聚次黄嘌呤胞嘧啶核苷酸[Poly(I∶C)],继续培养24 h,于48 h收集DC细胞,即48 h Poly(I∶C)组;第二组在24 h加入肿瘤坏死因子α(TNF-α),继续培养24 h,于48 h收集DC细胞,即48 h TNF-α组;第三组在36 h加入Poly(I∶C),继续培养36 h,在72 h时收获DC细胞,即72 h Poly(I∶C)组;第四组在36 h加入TNF-α,继续培养36 h,于72 h收集DC细胞,即72 hTNF-α组。同时设立对照组,仅加GM-CSF和IL-4。结果:经流式细胞仪检测72 h Poly(I∶C)组获得的成熟DC细胞的百分比含量最高;混合淋巴细胞培养(MLC)表明72 h Poly(I∶C)组获得的DC细胞具有较强的刺激淋巴细胞增殖的能力。结论:Poly(I∶C)诱导下人外周血DC的体外培养与成熟的方法是具有快速、稳定、经济、简便的特点,为DC的深入研究和临床应用奠定了基础。
文摘Aim-The aim of this study was to determine the safety and the efficacy of a gemcitabine/oxaliplatin combination (GEMOX) as first line therapy in patients with metastatic or unresectable locally-advanced pancreatic cancer. Patients and methods-Patients received gemcitabine 1000 mg/m2 as a 10 mg/m2/min infusion on day 1 followed on day 2 by oxaliplatin 100 mg/m2 as a 2 hour infusion, each cycle being given every 2 weeks. All patients had measurable disease and histological diagnosis before inclusion. Patients were treated until progression or for 12 cycles in the absence of progression. Tumor lesions were assessed by computed tomography scan every 4 cycles. Results-Between January 2001 and January 2003, 32 patients were eligible for the study. The objective response rate (OR) was 28.1%with a 12.5%complete response rate (CR). Median progression-free survival and median overall survival were 7 and 9 months, respectively. Median overall survival for patients with metastatic disease and locally-advanced disease were 7 and 25 months, respectively (P < 0.0007). Eleven patients were alive at 1 year (34.4%), six at 2 years (18.8%) and two at 3 years (6%). Fourteen (43.8%) of 32 patients experienced a clinical benefit response. Conclusion-These results support the safety, the antitumor activity and the possibility of durable responses of the GEMOX regimen in patientswith locally-advanced disease.
文摘Mutations in activation-induced cytidine deaminase can cause an autosomal rec essive form of hyper-IgM syndrome. We have examined a Tunisian family composed of six members: two healthy parents, their two healthy daughters and two affecte d sons. We found a homozygous transversion G to T in the two sons while heterozy gosity for the mutation was found in all other family members. This alteration i s localised in intron 2 at the +1 position resulting in defective splicing. Use of various intronic cryptic splice-sites led to expression of various aberrant mRNA species. Conclusion: This is a novel mutation found in the gene encoding f or activation-induced cytidine deaminase in a Tunisian family with hyper-IgM t ype 2 syndrome. This alteration leads to the use of two cryptic splicing sites c ausing the formation of two different mRNA species.
文摘Objectives.:Platinum resistance is a significant problem in patients with ovarian cancer. The aim of this phase II study was to define the response rates,the progression-free survival and the toxicity profile of the combination of PEG liposomal doxorubicin (L-DXR) and gemcitabine (GEM). Material and methods.:Thirty one patients with histologically confirmed platinum-refractory or-resistant epithelial ovarian cancer were scheduled to receive 6 cycles of L-DXR 30 mg/m2 on day 1 as well as GEM 650 mg/m2 on days 1 and 8 every 28 days. Results.:The median number of chemotherapy cycles given was 4. The mean dose intensity for L-DXR and GEM on day 1 was 96%and 97%,respectively. The mean dose intensity for GEM on day 8 was 93%. The overall response rate was 33%(10 of 30 evaluable patients; 20%complete responses). The median progression-free survival was 3.8 months,and the median overall survival was 15.8 months,respectively. Toxicity was acceptable. One quarter of patients developed grade 3 or 4 neutropenia,but none developed febrile neutropenia. Palmoplantar erythrodysesthesia (PPE) grades 2 and 3 occurred in 13%and 3%only,respectively,and no grade 4 PPE was observed. Grades 1 to 3 stomatitis was found in 58%of patients (10%grade 3). Conclusion.:The combination of L-DXR and GEM is an active and acceptably tolerated option in the treatment of patients with platinum-resistant and-refractory ovarian cancer. Dose reductions seem advisable in the case of ≥grade 2 stomatitis and/or PPE ≥grade 2.
文摘Background.:To determine the pathologic complete response rate of advanced ovarian cancer to weekly paclitaxel plus gemcitabine and carboplatin with filgrastim,and assess the longitudinal impact of this regimen on quality-of-life and cognitive functioning. Methods.:Fourteen patients with advanced ovarian,peritoneal,or fallopian tube cancer were treated in the phase I portion of the study. Initial doses were paclitaxel:60 mg/m2 days 1,8,and 15; gemcitabine:800 mg/m2 days 1 and 8; and carboplatin:area under the curve (AUC) 5 day 1,every 21 days for 6 cycles with filgrastim. Twenty-seven patients were treated at the phase II dose. Pathologic response was assessed by second-look laparoscopy in patients with complete response. Patients completed longitudinal assess- ments of quality-of-life and cognitive functioning. Results.:Maximally tolerated doses were paclitaxel:80 mg/m2 days 1 and 8; gemcitabine:800 mg/m2 days 1 and 8; and carboplatin:AUC 5 day 1,every 21 days. Forty-eight percent of patients (13/27) experienced at least 1 grade 3 nonhematologic toxicity. Fifty percent (95%confidence interval CI ,31-69%) of assessable patients achieved pathologic complete response. Median progression-free survival was 27.3 months (95%CI,17.7 months to not reached),and overall survival 43.6 months (95%CI,42 months to not reached). Cognitive functioning did not decline during or after chemotherapy. More highly educated women reported a perceived decline in concentration and memory while on chemotherapy. Quality-of-life scores were maintained during therapy. Conclusions.:Fifty percent of patients with advanced stage ovarian cancer achieved pathologic complete response to weekly paclitaxel plus gemcitabine and carboplatin. Cognitive functioning did not decline by objective measures,although highly educated women reported subjective impairment.
