Short-term results of a phase II study of preoperative docetaxel/cisplatin/S-1 therapy for locally advanced gastric cancer.
- 作者列表："Tsuchida K","Sato T","Aoyama T","Atsumi Y","Kano K","Maezawa Y","Kazama K","Numata M","Yamada T","Tamagawa H","Murakami H","Oshima T","Saeki H","Cho H","Yukawa N","Yamamoto Y","Masuda M","Rino Y
BACKGROUND:A multi-institutional phase II study was conducted to evaluate the efficacy and safety of preoperative docetaxel, cisplatin and S-1 therapy in marginally resectable advanced gastric cancer. METHODS:Patients with macroscopic type 4, large macroscopic type 3 and bulky lymph node metastasis received two cycles of preoperative docetaxel, cisplatin and S-1 therapy (docetaxel 40 mg/m2 and cisplatin 60 mg/m2 on day 1, and S-1 80 mg/m2 for 14 days, every 4 weeks). The primary endpoint was the pathological response rate, with an expected value of 65%. RESULTS:Thirty-one patients were enrolled in this study. The pathological response rate was 54.8%, and it was higher than the threshold value but lower than the expected rate. The R0 resection rate was 93.5%. The frequencies of grade 3-4 toxicities during docetaxel, cisplatin and S-1 therapy were 41.9% for neutropenia, 6.5% for febrile neutropenia and 32.3% for nausea/vomiting. Grade 2 and 3 surgical morbidities occurred in 23.3 and 6.7% of the patients, respectively. CONCLUSIONS:Preoperative docetaxel, cisplatin and S-1 therapy was feasible in terms of chemotherapy-related toxicities and surgical morbidity, but the effect did not achieve the expected value. The association between the pathological response rate and survival will be evaluated in the final analysis of this clinical trial.
背景: 一项多机构II期研究旨在评估术前多西他赛、顺铂和S-1治疗对局部可切除进展期胃癌的疗效和安全性。 方法: 肉眼可见的4型、肉眼可见的3型、巨大淋巴结转移的患者接受术前多西他赛、顺铂和S-1治疗2个周期 (多西他赛40 mg/m2和顺铂60 mg/m2，S-1 80 mg/m2，14天，每4周)。主要终点为病理缓解率，预期值为65%。 结果: 31例患者入选本研究。病理反应率为54.8%，高于阈值但低于预期率。基本传染数切除率为93.5%。多西他赛、顺铂和S-1治疗期间3-4级毒性的频率为中性粒细胞减少41.9%，发热性中性粒细胞减少6.5% 和恶心/呕吐32.3%。2级和3级手术发病率分别为23.3和6.7%。 结论: 术前多西他赛、顺铂、S-1方案治疗在化疗相关毒性反应和手术并发症方面是可行的，但效果未达到预期价值。病理反应率和存活率之间的关联将在本临床试验的最终分析中进行评估。
METHODS::The ATP binding-cassette superfamily corresponds the mostly transmembrane transporters family found in humans. These proteins actively transport endogenous and exogenous substrates through biological membranes in body tissues, so they have an important role in the regulation of many physiological functions necessary for human homeostasis, as well as in response regulation to several pharmacological substrates. The development of multidrug resistance has become one of the main troubles in conventional chemotherapy in different illnesses including cancer, being the increased efflux of antineoplastic drugs the main reason for this multidrug resistance, with a key role of the ABC superfamily. Likely, the interindividual variability in the pharmacological response among patients is well known, and may be due to intrinsically factors of the disease, genetic and environmental ones. Thus, the understanding of this variability, especially the genetic variability associated with the efficacy and toxicity of drugs, can provide a safer and more effective pharmacological treatment, so ABC genes are considered as important regulators due to their relationship with the reduction in pharmacological response. In this review, updated information about transporters belonging to this superfamily was collected, the possible role of these transporters in cancer, the role of genetic variability in their genes, as well as some therapeutic tools that have been tried to raise against main transporters associated with chemoresistance in cancer.
METHODS:BACKGROUND:Cholinergic neurotransmission regulates neuroinflammation in Parkinson disease (PD). RESEARCH DESIGN AND METHODS:The authors conducted a delayed-start study of donepezil for cognitive decline in non-demented PD patients. The study consisted of a 96-week randomized placebo-controlled double-blind phase 1, followed by a 24-week donepezil extension phase 2. The primary outcome measure was a change in the Mini-Mental State Examination (MMSE) at week 120. RESULTS:A total of 98 patients were randomly allocated to the early-start (donepezil-to-donepezil) and delayed-start (placebo-to-donepezil) groups. Mean (SD) of the baseline MMSE was 27.6 (2.0) and 28.0 (2.1), respectively. MMSE change at week 120 was better in the early-start group than in the delayed-start group, but the difference was not significant. The MMSE declined in apolipoprotein ε4 carriers, but not in non-carriers, and the factor interaction (intervention × ε4 genotype) was highly significant (P < 0.001). Analyzed with the interaction, the difference was significant (group difference 1.95 [0.33 to 3.57], P = 0.018). The MMSE decline slope in phase 1 was significantly better in the early-start group than in the delayed-start group (P = 0.048). CONCLUSIONS:Cognitive function deteriorated in ε4 carriers, but not in non-carriers, and early-start donepezil may postpone cognitive decline in the former.
METHODS::Since the discovery of dental pulp stem cells, a lot of teams have expressed an interest in dental pulp regeneration. Many approaches, experimental models and biological explorations have been developed, each including the use of stem cells and scaffolds with the final goal being clinical application in humans. In this review, the authors' objective was to compare the experimental models and strategies used for the development of biomaterials for tissue engineering of dental pulp with stem cells. Electronic queries were conducted on PubMed using the following terms: pulp regeneration, scaffold, stem cells, tissue engineering and biomaterial. The extracted data included the following information: the strategy envisaged, the type of stem cells, the experimental models, the exploration or analysis methods, the cytotoxicity or viability or proliferation cellular tests, the tests of scaffold antibacterial properties and take into account the vascularization of the regenerated dental pulp. From the 71 selected articles, 59% focused on the "cell-transplantation" strategy, 82% used in vitro experimentation, 58% in vivo animal models and only one described an in vivo in situ human clinical study. 87% used dental pulp stem cells. A majority of the studies reported histology (75%) and immunohistochemistry explorations (66%). 73% mentioned the use of cytotoxicity, proliferation or viability tests. 48% took vascularization into account but only 6% studied the antibacterial properties of the scaffolds. This article gives an overview of the methods used to regenerate dental pulp from stem cells and should help researchers create the best development strategies for research in this field.