Cisplatin-induced long-term dynorphin A-immunoreactivity in cell somata of rat area postrema neurons

We evaluated long-term dynorphin A-immunoreactivity in the rat area postrema (AP) after the administration of cisplatin. First, rats were given 1, 5 and 10 mg/kg body weight cisplatin (i.p.) and their behavior was monitored for 72 h. We observed a delayed increase in pica 24-72 h after injection, compared to the 24 h before injection. We attributed this to the cisplatin injection. Pica was defined as an increase in the intake of non-nutritional matter such as kaolin. Administration of 1, 5 and 10 mg/kg cisplatin led to an increase in kaolin intake on day 1. Administration of 5 and 10 mg/kg of cisplatin led to decreased intake of laboratory chow (MF) on days 1–3, but 10 mg/kg cisplatin causes an excessive aggravation of their condition. Following this behavioral experiment, we immunohistochemically examined the induction of dynorphin A in the AP at 24, 48 and 72 h post-administration of 1 and 5 mg/kg cisplatin. Administration of 5 mg/kg cisplatin caused dynorphin A to accumulate gradually in the neurosoma of the AP neurons, and the numbers of positive AP neurosomata at 48 and 72 h post-administration were higher than following an equal dosage of 0.9% NaCl. These findings suggest that dynorphin A increases in the central nervous system for a long time following administration, and causes certain behavioral and clinical changes, including those related to appetite and nausea.     

Therapeutic effect of adipose-derived mesenchymal stem cells on Cisplatin induced testicular damage in adult male albino rat

Infertility represents a major medical, economic, and psychological problem. Stem cells therapy for infertility has a great interest nowadays especially for cancer survivors at pre-reproductive and reproductive age.

 Thirty-two adult male albino rats were used, divided equally into four groups; Group I (Control group) received isotonic saline intraperitoneally (i.p.) as vehicle. Group II (Cisplatin-treated group) received Cisplatin (i.p.) at a single dose of 7 mg/kg, and then were sacrificed after 5 days. Group III (Stem-cell-treated group) received Cisplatin (i.p.) at a single dose of 7 mg/kg, then after 5 days received adipose-derived mesenchymal stem cells (ADMSCs) (1 × 10⁶). Cells were injected in the rete testis, then after 60 days, the animals were sacrificed. Group IV (Auto healing group) received Cisplatin (i.p.) at a single dose of 7 mg/kg, and then left for 65 days then the animals were sacrificed. Cisplatin administration resulted in degenerative changes in the testicular architecture in the form of thickened irregular BM of seminiferous tubules. The germinal epithelium showed disorganization and marked reduction in the thickness, associated with Sertoli cells preservation. Features of apoptosis assured by elevated caspase-3 expression were noticed. The interstitium showed cellular infiltration and distorted Leydig cells. Injection of (ADMSCs) resulted in great improvement of testicular architecture and increase in the testosterone level associated with strong immune reaction of the CD-44. ADMSCs are recommended as a new treatment modality for male infertility.

Abbreviation: i.p.: intraperitoneally; BM: basement membrane; ADMSCs: adipose-derived mesenchymal stem cells; WHO: World Health Organization; MSCs: mesenchymal stem cells; DMEM: Dulbecco modified eagles media; PBS: phosphate-buffered saline; FACS: fluorescence-activated cell sorting; ELISA: enzyme-linked immunosorbent assay; CP: Cisplatin; ROS: reactive oxygen species; CAT: catalase; SOD: superoxide dismutase; OS: oxidative stress; SSCs: spermatogonia stem cells; GCs: germ cells; UCMSCs: umblical cord mesenchymal stem cells; TGFb1: transforming growth factor beta-1; BMP4: Bone morphogenic protein 4; BMP8b: bone morphogenic protein 8b.     

A Randomized Study of Epithelial Ovarian Cancer: Is Chemotherapy Useful after Complete Remission?

Objective. The aim of this study is to verify whether consolidation chemotherapy with Cisplatin improves disease-free survival and/or overall survival in patients affected by epithelial ovarian cancer.Methods. A multicenter study examined 122 randomized patients in complete remission as judged by laparoscopy or laparotomy following first-line chemotherapy consisting of ACy (Adriamycin + Cyclophosphamide), PCy (Cisplatin + Cyclophosphamide), or Mitoxantrone + Carboplatin. Sixty-one of these patients were treated with 3 cycles of 5-Fluorouracil (FU) 500 mg/m2 for 5 days followed by Cisplatin at 100 mg/m2 on the 6th or 7th day every 28 days; the other 61 received no further treatment (nihil group).Results. Sixty patients in the Cisplatin arm were evaluable. There were 36 relapses in the FU+Cisplatin arm and 30 in the nihil arm. Peritoneal relapses were 25% for Cisplatin treatment vs. 16.4 % for nihil. There were 29 deaths in the Cisplatin arm vs. 27 for nihil. Median overall survival time (95 months with Cisplatin vs. 96 months in the nihil group) and median disease-free survival (66 months with Cisplatin vs. 73 in the nihil group) were similar in both arms (p=0.66 and p=0.41, respectively). There were no significant differences in tumor stage and grade between the two arms. Seven patients presented a second neoplasm during follow-up: six in the nihil arm, but only one patient in the Cisplatin arm. Death in these patients was due to the second neoplasm and not to progression of ovarian cancer.Conclusion. Three courses of additional platinum+FU treatment after five cycles of first-line chemotherapy without FU produced no increase in overall survival or disease-free survival.     

重组人p53腺病毒注射液联合顺铂与紫杉醇治疗晚期宫颈癌的疗效及安全性分析

目的探讨重组人p53腺病毒注射液联合顺铂与紫杉醇治疗晚期宫颈癌的疗效及安全性。方法 80例晚期宫颈癌患者随机分为两组各40例,对照组给予顺铂与紫杉醇治疗,研究组在对照组基础上给予重组人p53腺病毒注射液治疗。比较两组的治疗效果、不良反应以及复发率、转移率、死亡率。结果研究组的治疗总有效率高于对照组,1年内病死率、复发率及转移率均低于对照组(P <0.05)。两组的不良反应发生率比较,差异无统计学意义(P>0.05)。结论重组人p53腺病毒注射液联合顺铂与紫杉醇治疗晚期宫颈癌患者的疗效显著,安全性高,能够有效减少近期死亡、复发及转移。     

实验性顺铂诱导急性肾功能衰竭动物模型的研究

1目的　建立顺铂 (cisplatin,CP)诱导的急性肾功能衰竭 (acute renal failure,ARF )大鼠模型 ,探讨 ARF的发病机制。2方法　 SD大鼠静脉一次性注射 CP 6 mg/ kg,动态观察大鼠血清肌酐 (Scr)、尿素氮 (BUN)变化以及肾组织形态学改变。 3结果　对照组不同时间 Scr、BUN差异不明显 (P>0 .0 5 ) ,肾组织形态学正常。模型组 Scr、BUN第 4d较第 1d明显升高 (P<0 .0 5 )。肾组织形态学显示 ,肾脏髓质外侧带大部分肾小管坏死 ,细胞核固缩、溶解、消失 ,管腔扩张 ,有坏死脱落碎屑。 4结论　 CP诱导的大鼠 ARF模型为一较为理想的 ARF模型     

Utilidad de la quimioterapia neoadyuvante en el carcinoma vesical músculo invasivo no metastásico

ObjectiveWe analyzed the profile of patients who were candidates for neoadjuvant chemotherapy (NACT) in stage pT2-4aN0M0, the tolerability and adherence of our cisplatin-based protocol and oncological outcomes.Material and methodsRetrospective observational cohort study including patients diagnosed with muscle-invasive bladder carcinoma treated with NACT. Clinical, histopathological, therapeutic and evolutionary characteristics of the patients were analyzed. The use of NACT was evaluated by the complete response in the surgical specimen (pT0). This and other pathological factors were related to overall survival and progression-free survival.ResultsWe included 90 patients with muscle-invasive bladder carcinoma (clinical stage T2a-T4aN0M0) who received a cisplatin-based NACT regimen between January 2011 and December 2018, prior to radical surgery. Forty percent of patients presented an adverse reaction, with a compliance with the NACT regimen of 92.2%. There were no deaths related to systemic treatment and no adverse reaction to treatment made radical cystectomy impracticable. After performing radical cystectomy, the presence of complete response (pT0) was observed in 20 patients (21%), lower stage in the surgical specimen (<pT2) in 36 patients (40%), positive surgical margins in 7 patients (8%), lymph node involvement (N1) in 16 patients (17.8%). A shorter time to progression was observed in the group of patients who did not achieve a complete pathological response (53 months vs. 83.1 in pT0 patients, P = 0.012), in patients with lymph node involvement compared to pN0 (65.4 vs. 28, 2 months, P = 0.014) and in those with positive surgical margins compared to those with tumor-free margins (63.5 vs. 8.5 months, P = 0.021).ConclusionThe adequate selection of patients with muscle-invasive bladder carcinoma has shown a good tolerance to NACT, with a high compliance rate prior to RC. The improvement in the complete response rate implies a greater survival in this group of patients, with lymph node involvement and positive surgical margins being important prognostic factors.     

PF方案化放治疗晚期鼻咽癌的远期疗效

目的探索用ＰＤＤ／５－Ｆｕ方案化放治疗晚期鼻咽癌的疗效。方法１９８９年１２月～１９９０年１２月间,选择７６例Ⅲ、Ⅳ期鼻咽癌患者,先作３周期ＰＤＤ（２０ｍｇ（ｍ２）－１ｄ－１,ｉｖ,第１～５天）和５－Ｆｕ［７００ｍｇ（ｍ２）－１ｄ－１,连续静脉滴注,第１～５天］诱导化疗,随后尽快作放疗,此为综合治疗组。以１９８９年作单纯放疗的８６例晚期鼻咽癌患者作对照组。两组放疗方法、时间／剂量分割均相同。结果化疗有效率为８９．３％,完全缓解率为１８．４％。综合治疗组（综合组）总的５年生存率为４８．７％,对照组为３３．７％（Ｐ＞０．０５）。综合组Ｔ２Ｎ３和Ｔ２～４Ｎ３患者的５年生存率为４４．１％和３９．５％,均明显高于对照组的２１．６％及２０．４％（Ｐ＜０．０５）。结论ＰＦ方案化放治疗提高了Ｔ２～４Ｎ３患者的５年生存率。     

Lipopolysaccharide-induced platinum accumulation in the cerebral cortex after cisplatin administration in mice: Involvement of free radicals

The relationship between the accumulation of platinum in the cerebral cortex following cisplatin administration and injury to the blood-brain barrier after lipopolysaccharide (LPS) treatment was investigated. The appearance of intravenously injected fluorescein in the brain was significantly increased 10–24 h after LPS treatment, the effect being dose-dependent. Platinum was detectable in the cerebral cortex of cisplatin-treated mice 24 h after LPS treatment, but not without LPS treatment. In mice pretreated with -tocopherol, LPS administration did not significantly augment fluorescein penetration into the brain, whereas pretreatment with either allopurinol or ascorbic acid did not modify the LPS-induced increase in fluorescein penetration. In contrast, platinum in the cerebral cortex after cisplatin administration was still detectable in the allopurinol-, ascorbic acid-, and -tocopherol-pretreated groups, and the levels of platinum in these groups were not significantly different from those in the group treated with LPS only. Administration of superoxide dismutase (SOD), but not of catalase, tended to inhibit the penetration of fluorescein. Both SOD and catalase significantly lowered platinum content in the cerebral cortex following cisplatin administration in mice treated with LPS. Thus, free radicals may injure the blood-brain barrier in mice challenged with LPS, and allow cisplatin to penetrate into the cerebral cortex, resulting in platinum accumulation.     

谷胱甘肽对顺铂致猴和大鼠肾细胞毒性的影响

目的 探讨顺铂对猴和大鼠肾小管上皮细胞的毒性及半胱氨酸和GSH合成抑制剂BSO对其影响。方法 从猴和大鼠的肾脏分离培养的肾小管上皮细胞接种于96孔培养板，培养24h后加入一系列浓度的顺铂，或在加入顺铂前16和4h，分别加入GSH合成抑制剂BSO和GSH的前体物半胱氨酸，继续培养，分别在8、24和48h3个时间点用MTT方法检测细胞存活率。结果 顺铂对猴和大鼠肾小管上皮细胞有明显的毒性，在不同的时间点有各自的剂量—反应关系，顺铂对大鼠肾小管上皮细胞在8、24和48h 3个时间点半数抑制浓度(IC50)分别为1105．12、513．25和71．24μmol/L；BSO能使3组IC50均降低，分别为66．00、21．43和7．23μmol/L，而半胱氨酸则使3组IC50均升高，均大于5000μmol/L；顺铂对猴肾小管上皮细胞在3个时间点IC50分别为3026．00、1238．35和664．44μmol/L；BS0使3组ICD分别降为480．10、108．61和31．43μmol/L，而半胱氨酸则可使3组IC50均大于5000μmol/L。结论 顺铂对猴和大鼠肾小管上皮细胞均具有明显毒性作用，对猴的毒性低于大鼠；BS0可增强顺铂的细胞毒性，对大鼠的影响大于猴，而半胱氨酸对两种细胞的保护作用无显著性差异，提示细胞内GSH对顺铂所致肾小管上皮细胞毒性有保护作用。     

NP与MNP方案治疗NSCLC近期疗效及毒性的对比分析

目的 :对比观察二药和三药联合化疗方案治疗非小细胞肺癌 (NSCLC)的近期疗效和毒性反应。方法 :6 2例初治的Ⅲb～Ⅳ期NSCLC ,随机分成A组 (去甲长春新碱 2 5mg/m2 静注第 1、8天 +顺铂 80mg/m2 静滴 ,分 2天 ,即NP方案 )、B组 (丝裂霉素 6mg/m2 静注第 1天 +去甲长春新碱 2 5mg/m2 静注第 1、8天 +顺铂 80mg/m2 静滴 ,分 2天 ,即MNP方案 )两组 ,分别化疗 2周期 ,每 4周为一周期。结果 :A组有效率为 33 3%、B组有效率为 37 9% (P >0 0 5 ) ;血小板降低A组为33 3% ,B组为 5 8 6 % (P <0 0 5 )。两组其余毒性反应无显著差异。结论 :二药联合可能比三药联合毒性低 ,而有效率无显著差异。