Survival and prognostic association in stage IV colorectal cancer patients treated with chemotherapy in Bangladesh.
- 作者列表："Shuayb M","Mehedi Hasan M","Hoque MR","Mushtaq Hussain Q","Begum R","Reza MS
OBJECTIVE:Prognostic factors in colorectal cancer have lesser been evaluated in developing countries. This study aims to determine overall survival and prognostic factors for metastatic colorectal cancer patients who were non-operable and received chemotherapy. METHODS:The study retrospectively investigated 67 inoperable metastatic colorectal cancer patients at Square Hospital, Bangladesh. The primary endpoint was overall survival, and the secondary endpoints were prognostic association with factors. Survival probabilities were calculated by non-parametric Kaplan-Meier method and compared by log-rank test. Univariate and multivariable Cox proportional hazard models were implemented to assess the prognostic association. RESULTS:Median survival of the entire cohort was 14 months (95% confidence interval: 11-25). In multivariable analysis, two prognostic factors were independently associated with survival: Karnofsky performance status and carcinoembryonic antigen. Patients with Karnofsky performance status <70 had significant higher risk of death than those with Karnofsky performance status ≥70 (adjusted hazard ratio 4.25, 95% confidence interval: 2.15-8.39). Higher risk of death was found to be associated with higher carcinoembryonic antigen: adjusted hazard ratio was 1.72 (95% confidence interval: 0.81-3.68) and 2.96 (95% confidence interval: 1.25-7.01) for patients with carcinoembryonic antigen 10-100 and >100 ng/ml, respectively, while comparing with carcinoembryonic antigen <10 ng/ml. The presence of peritoneal metastasis and grade-III tumour significantly worsened the survival in univariate analysis (hazard ratio 2.46, 95% confidence interval: 1.32-4.57 and hazard ratio 1.74, 95% confidence interval: 1.01-3.03, respectively) but not in multivariable analysis (adjusted hazard ratio 1.92, 95% confidence interval: 0.88-4.18 and adjusted hazard ratio 1.25, 95% confidence interval: 0.66-2.36, respectively). CONCLUSION:The study reported survival of stage IV colorectal cancer patients undergo chemotherapy and identified that Karnofsky performance status and carcinoembryonic antigen are the poor prognostic factors to this cohort adjusting for other factors.
目的: 在发展中国家，结直肠癌预后因素的评估较少。本研究旨在确定不可手术且接受化疗的转移性结直肠癌患者的总生存期和预后因素。 方法: 本研究回顾性调查了孟加拉国广场医院67例不能手术的转移性结直肠癌患者。主要终点为总生存期，次要终点为预后相关因素。通过非参数Kaplan-Meier方法计算生存概率，并通过时序检验进行比较。采用单变量和多变量Cox比例风险模型评估预后相关性。 结果: 整个队列的中位生存期为14个月 (95% 置信区间: 11-25)。在多变量分析中，两个预后因素与生存独立相关: Karnofsky性能状态和癌胚抗原。Karnofsky体能状态 <70的患者死亡风险显著高于Karnofsky体能状态 ≥ 70的患者 (校正风险比4.25，95% 置信区间: 2.15-8.39).发现较高的死亡风险与较高的癌胚抗原相关: 对于癌胚抗原10-1.72和> 95% ng/ml的患者，校正风险比分别为0.81 (3.68置信区间: 2.96-95%) 和1.25 (7.01置信区间: 100-100)，同时与癌胚抗原 <10 ng/ml比较。在单变量分析中 (风险比2.46，95% 置信区间: 1.32-4.57和风险比1.74，95% 置信区间: 1.01-3.03)，腹膜转移和III级肿瘤的存在显著恶化了生存，但在多变量分析中没有 (调整后的风险比1.92，95% 置信区间: 0.88-4.18和调整后的危险比1.25，95% 置信区间: 分别为0.66-2.36)。 结论: 该研究报告了接受化疗的IV期结直肠癌患者的生存情况，并确定Karnofsky表现状态和癌胚抗原是该队列中调整其他因素的不良预后因素。
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.