Degarelix as a neoadjuvant hormonal therapy for acute urinary tract toxicity associated with external beam radiotherapy for intermediate- and high-risk prostate cancer: a propensity score matched analysis.
- 作者列表："Hata S","Shin T","Abe S","Kawano K","Sato R","Kai T","Shibuya T","Ando T","Mimata H
BACKGROUND:In prostate cancer treatment, lower urinary tract symptoms significantly improve with luteinizing hormone-releasing hormone antagonists use compared with agonists. However, it is unclear whether luteinizing hormone-releasing hormone antagonists can decrease acute urinary tract toxicity during external beam radiotherapy. This study aimed to assess whether luteinizing hormone-releasing hormone antagonists used as neoadjuvant therapy reduced acute urinary tract toxicity during external beam radiotherapy compared with luteinizing hormone-releasing hormone agonists. METHODS:The study included 78 patients who underwent intensity-modulated radiation therapy for intermediate- and high-risk prostate cancer between April 2013 and January 2020. Irradiation was initiated after 3-6 months of neoadjuvant therapy. Androgen deprivation therapy was given to the intermediate-risk group for 6 months and the high-risk group for 2-3 years. The European Organization for Research and Treatment of Cancer/Radiation Therapy Oncology Group toxicity grading scale was used to evaluate the urinary tract system toxicity. Relevant clinical factors were used in matching patients based on propensity scores to enable comparison between the groups. RESULTS:Each group had 27 matched patients. There was no reduction in urinary tract toxicity with the use of luteinizing hormone-releasing hormon antagonists (P = 0.624). For patients with an International Prostate Symptom Score of ≥11 at the start of treatment, 18 patients in each group were matched. Significantly lower scores were observed in the luteinizing hormone-releasing hormon antagonist group (P = 0.041). CONCLUSIONS:Luteinizing hormone-releasing hormon antagonists may reduce acute urinary tract toxicity during prostate cancer external beam radiotherapy compared with luteinizing hormone-releasing hormon agonists, in particular in patients with moderate to severe symptoms at the start of treatment.
背景: 在前列腺癌治疗中，与激动剂相比，使用促黄体生成素释放激素拮抗剂可显著改善下尿路症状。然而，目前尚不清楚促黄体生成素释放激素拮抗剂是否可以减少外照射放疗期间的急性尿路毒性。本研究旨在评估与促黄体生成素释放激素激动剂相比，作为新辅助治疗的促黄体生成素释放激素拮抗剂是否减少了外照射放疗期间的急性尿路毒性。 方法: 本研究纳入了78例在2013年4月至2020年1月间接受调强放疗的中高危前列腺癌患者。新辅助治疗3-6个月后开始放疗。中危组给予雄激素剥夺治疗6个月，高危组给予2 ~欧洲癌症研究和治疗组织/放射疗法肿瘤学组毒性分级量表用于评价泌尿道系统毒性。相关临床因素用于基于倾向评分匹配患者，以实现组间比较。 结果: 每组有27名匹配的患者。使用促黄体生成素释放激素拮抗剂没有减少尿路毒性 (P = 0.624)。对于治疗开始时国际前列腺症状评分 ≥ 11分的患者，每组匹配18例。在促黄体生成素释放激素拮抗剂组中观察到显著较低的评分 (P = 0.041)。 结论: 与促黄体激素释放激素激动剂相比，促黄体激素释放激素拮抗剂可减轻前列腺癌外照射放疗期间的急性尿路毒性，特别是在治疗开始时有中度至重度症状的患者中。
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.