阿帕替尼对卵巢癌术后复发铂类耐药的影响

目的 探讨阿帕替尼治疗卵巢癌术后复发铂类耐药的临床价值.方法 选择2017年10月至2019年3月期间邢台市人民医院66例卵巢癌术后复发铂类耐药的病人作为研究对象,采用随机数字表法分为阿帕替尼联合化疗组、化疗组及阿帕替尼单药组,各22例.其中联合化疗组给予阿帕替尼+多西他赛(或吉西他滨)治疗,4个周期后阿帕替尼单药维持...     

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.     

Cytotoxic efficacy of an anthraquinone linked platinum anticancer drug

Platinum complexes are widely used in cancer chemotherapy; however, they are associated with toxicity, high "non-specific" reactivity and relatively poor pharmacokinetic profiles. In particular, their low cellular uptake and rapid metabolic inactivation means that the amount of "active" drug reaching the nuclear compartment is low. Our strategy to facilitate nuclear accumulation was to introduce a hydrophobic anthraquinone (1C3) moiety to the Pt-complex. Anthraquinones are known to readily intercalate into DNA strands and hence, the Pt-1C3 complex may represent an effective system for the delivery of the platinum moiety to nuclear DNA. Efficacy of the complex was determined by measuring the extent and potency of cytotoxicity in comparison to cisplatin and an anthraquinone based anticancer drug, doxorubicin. The Pt-1C3 complex generated higher levels of cytotoxicity than cisplatin, with a potency of 19 +/- 4 microM in the DLD-1 cancer cell line. However, this potency was not significantly different to that of the 1C3 moiety alone. To examine the reason for the apparent lack of platinum related cytotoxicity, the cellular distribution was characterised. Confocal fluorescence microscopy indicated that the Pt-1C3 complex was rapidly sequestered into lysosomes, in contrast to the nuclear localisation of doxorubicin. In addition, there was negligible DNA associated Pt following administration of the novel complex. Thus, the addition of a 1C3 moiety generated sequestration of the complex to lysosomes, thereby preventing localisation to the nucleus.     

Prevalence of respiratory allergy in a platinum refinery

Summary In a cross-sectional study, 65 workers in the chemical industry with exposure to platinum salts were investigated with regard to the prevalence to allergic respiratory tract diseases. A respriatory questionnaire, a skin-prick test with K₂PtCl₆ and environmental allergens, determination of total IgE, platinum-specific IgE and histamine release in basophilic granulocytes and lung function tests were applied before and after a Monday shift and after a Friday shift. Work-related symptoms of respiratory allergy were present in 23% of all workers, but were significantly more frequent in the most exposed group in the platinum refinery (52.4%). Of all workers, 18.7% had a positive skin-prick test with platinum salt. As compared to the other workers, the workers with work-related symptoms of respiratory allergy had significantly more positive skin-prick tests (64.3%) and a higher total IgE and platinum-specific IgE; they did not, however, show higher histamine release. In the course of the week, a significant fall in lung function, namely in FEV₁ and FEF25, was recorded in the group of workers with work-related symptoms.     

Antineoplastic drug residues inside homes of chemotherapy patients

Chemotherapy treatment of cancer patients has shifted from inpatient to outpatient administration. Thus, family members are potentially exposed to cytotoxic drug residues from patients’ excretions inside their homes. The study's aim was to evaluate the surface contamination and the potential uptake of antineoplastic drug residues by family members at home of chemotherapy patients. Overall, 265 wipe samples from 13 homes were taken at two times after chemotherapy from different surfaces (toilet, bathroom, kitchen). 62 urine samples were collected from patients and family members on three days. Samples were analyzed for cyclophosphamide, 5-fluorouracil (urine: FBAL) and platinum (as marker for cis-, carbo- and oxaliplatin). Substantial contamination was found on every surface type (PT: 0.02–42.5 pg/cm², 5-FU: ND-98.3 pg/cm², CP: ND-283.3 pg/cm²) with highest concentrations on toilet and bathroom surfaces. While patients’ urinary drug concentrations often were elevated for more than 48 h after administration, no drug residues were detectable in the family members’ urine. This study provided an insight in the exposure situation against antineoplastic drug residues at home of chemotherapy patients. As contamination could be found on various surfaces adequate hygienic and protective measures are necessary to minimize the exposure risk for cohabitants.     

The intestinal parasite Pomphorhynchus laevis as a sensitive accumulation indicator for the platinum group metals Pt, Pd, and Rh

Concentrations of the platinum group elements Pt, Pd, and Rh were analyzed by adsorptive cathodic stripping voltammetry (Pt, Rh) and total-reflection X-ray fluorescence (Pd) in the intestinal helminth Pomphorhynchus laevis and its host Barbus barbus. The fish were caught in the Danube river south of the city of Budapest (Hungary) and were exposed to ground catalytic material for 28 days. Following exposure all three precious metals were taken up and accumulated in host organs and the parasites. Interestingly, in all tissues of the unexposed controls Pt was found, whereas Pd was not present in the muscle of the controls and Rh was not detectable in muscle and intestine of unexposed barbel. All metals were found at significantly higher concentrations in the acanthocephalan than in the tissues of barbel. These results are discussed with respect to the application of P. laevis as an accumulation indicator for metals.     

铂复合盐与甲苯二异氰酸酯致敏大鼠体内抗原特异性IgG水平的观察

30只大鼠分成5组,分别用铂牛血清白蛋白结合物(Pt-BSA)及甲苯二异氰酸酯牛血清白蛋白结合物(TDI-BSA)加弗氏完全佐剂(CFA),以及单用BSA-CFA,NS,CFA作为对照给大鼠腹腔内注射进行免疫。分别于免疫前、免疫后2周、4周采血。用酶联免疫吸附实验(ELISA)以铂人血清白蛋白结合物(Pt-HSA)、甲苯二异氰酸酯人血清白蛋白结合物(TDI-HSA)为抗原,单克隆鼠抗大鼠IgG-HRPO抗体进行抗原特异性IgG(S-IgG)测定。结果发现用Pt-BSA、TDI-BSA致敏动物后,体内存在S-IgG,其水平随免疫时间的延长或加强免疫而递增。对照组不存在这种S-IgG的增加。用S-IgG抑制试验证明这种抗体具有明显的半抗原特异性。     

维生素C对顺铂诱导卵巢癌CAOV3细胞凋亡的影响

目的探讨维生素C是否能影响顺铂诱导卵巢癌CAOV3细胞凋亡,以及它对细胞内端粒酶活性的影响。方法MTT法和流式细胞术检测细胞生长和凋亡的情况,TRAP-ELISA法测定端粒酶活性变化。结果DDP联合AA作用组比单独用DDP组细胞凋亡率明显增高,端粒酶活性明显降低。单独10μmol/LDDP处理组细胞生长未受到明显抑制,但联合AA后其生长受到抑制。结论AA能增强DDP诱导卵巢癌CAOV3细胞凋亡,并增强DDP对细胞内端粒酶活性的抑制作用。     

Calculations of the exchange current density for hydrogen electrode reactions: A short review and a new equation

After reviewing relevant equations for the calculation of exchange current density, a new equation is derived for hydrogen electrode reactions to correct for the influences of the hydrogen concentration change in the vicinity to the electrode surface. This equation is able to describe the polarization curve shape in the small polarization region as well as to calculate the exchange current (density). The abilities of this equation are demonstrated by the data obtained with a Pt rotating disk electrode in 0.1 mol l⁻¹ KOH solution. The exchange current density at 298 K under 1 atmosphere hydrogen pressure is found to be 0.103 mA cm⁻² with an apparent activation energy of 33.5 kJ mol⁻¹. At a constant temperature, the exchange current is found to be proportional to the square root of the hydrogen partial pressure in the solution.     

Differences in the cellular response and signaling pathways of cisplatin and BBR3464 ([[trans-PtCl(NH3)(2)]2mu-(trans-Pt(NH3)(2)(H2N(CH2)(6)-NH2)2)]4+) influenced by copper homeostasis

[[trans-PtCl(NH(3))(2)](2)mu-(trans-Pt(NH(3))(2)(H(2)N(CH(2))(6)-NH(2))(2))](4+) (BBR3464) is a cationic trinuclear platinum drug that is being evaluated in phase II clinical trials for treatment of lung and ovarian cancers. The structure and DNA binding profile of BBR3464 is different from drugs commonly used clinically. It is of great interest to evaluate the difference between the mechanisms of uptake employed by BBR3464 and cisplatin (c-DDP), as altered uptake may explain chemoresistance. Using transfected cell lines, we show that both c-DDP and BBR3464 use the copper transporter hCTR1 to enter cells and to a lesser extent, the ATP7B transporter to exit cells. Copper influenced c-DDP and BBR3464 uptake similarly; it increased the c-DDP and BBR3464 uptake in ovarian (A2780) and colorectal (HCT116) carcinoma cell lines as detected by ICP-OES. However, the effects of copper on c-DDP- and BBR3464-mediated cytotoxicity differed. Copper decreased c-DDP-induced apoptosis, caspase-3/7 activation, p53 induction and PARP cleavage in cancer cell lines. In contrast, copper increased BBR3464-induced apoptosis, and had little effect on caspase activation, PARP cleavage, and p53 induction. It was concluded that BBR3464 employs mechanisms of intracellular action distinct from c-DDP. Although these drugs use the same cellular transporters (hCTR1 and ATP7B) for influx and efflux, downstream effects are different for the two drugs. These experiments illustrate fundamental differences in the mechanisms of action between cisplatin and the novel Pt-based drug BBR3464.