Efficacy of ronidazole for treatment of cats experimentally infected with a Korean isolate of Tritrichomonas foetus

To evaluate the efficacy of ronidazole for treatment of Tritrichomonas foetus infection, 6 Tritrichomonas-free kittens were experimentally infected with a Korean isolate of T. foetus. The experimental infection was confirmed by direct microscopy, culture, and single-tube nested PCR, and all cats demonstrated trophozoites of T. foetus by day 20 post-infection in the feces. From day 30 after the experimentally induced infection, 3 cats were treated with ronidazole (50 mg/kg twice a day for 14 days) and 3 other cats received placebo. Feces from each cat were tested for the presence of T. foetus by direct smear and culture of rectal swab samples using modified Diamond's medium once a week for 4 weeks. To confirm the culture results, the presence of T. foetus rRNA gene was determined by single-tube nested PCR assay. All 3 cats in the treatment group receiving ronidazole showed negative results for T. foetus infection during 2 weeks of treatment and 4 weeks follow-up by all detection methods used in this study. In contrast, rectal swab samples from cats in the control group were positive for T. foetus continuously throughout the study. The present study indicates that ronidazole is also effective to treat cats infected experimentally with a Korean isolate of T. foetus at a dose of 50 mg/kg twice a day for 14 days.     

Proteomic identification of predictive biomarkers of resistance to neoadjuvant chemotherapy in luminal breast cancer: a possible role for 14-3-3 theta/tau and tBID?

Introduction

Chemotherapy resistance is a major obstacle in effective neoadjuvant treatment for estrogen receptor-positive breast cancer. The ability to predict tumour response would allow chemotherapy administration to be directed towards only those patients who would benefit, thus maximising treatment efficiency. We aimed to identify putative protein biomarkers associated with chemotherapy resistance, using fresh tumour samples with antibody microarray analysis and then to perform pilot clinical validation experiments.

Materials and methods

Chemotherapy resistant and chemotherapy sensitive tumour samples were collected from breast cancer patients who had received anthracycline based neoadjuvant therapy consisting of epirubicin with cyclophosphamide followed by docetaxel. A total of 5 comparative proteomics experiments were performed using invasive ductal carcinomas which demonstrated estrogen receptor positivity (luminal subtype). Protein expression was compared between chemotherapy resistant and chemotherapy sensitive tumour samples using the Panorama XPRESS Profiler725 antibody microarray containing 725 antibodies from a wide variety of cell signalling and apoptosis pathways. A pilot series of archival samples was used for clinical validation of putative predictive biomarkers.

Results

AbMA analysis revealed 38 differentially expressed proteins which demonstrated at least 1.8 fold difference in expression in chemotherapy resistant tumours and 7 of these proteins (Zyxin, 14-3-3 theta/tau, tBID, Pinin, Bcl-xL, RIP and MyD88) were found in at least 2 experiments. Clinical validation in a pilot series of archival samples revealed 14-3-3 theta/tau and tBID to be significantly associated with chemotherapy resistance.

Conclusions

For the first time, antibody microarrays have been used to identify proteins associated with chemotherapy resistance using fresh breast cancer tissue. We propose a potential role for 14-3-3 theta/tau and tBID as predictive biomarkers of neoadjuvant chemotherapy resistance in breast cancer. Further validation in a larger sample series is now required.     

影响经动脉子宫颈癌热灌注化疗临床疗效的多因素分析

目的:探讨宫颈癌热灌注化疗栓塞的治疗作用及对临床疗效的影响因素分析。方法:对34例宫颈癌病人进行子宫动脉热灌注化疗及栓塞术,分析肿瘤病理类型,肿块大小,周围浸润及淋巴结转移情况等因素对介入治疗的影响。结果:经过对临床疗效的多因素分析肿块大小对治疗效果影响最大,其次为病理类型。其余影响较小。结论:宫颈癌热灌注化疗栓塞术是治疗宫颈癌的一种适合疗法,尤其适用于肿块较小的病人。可以使疾病得到有效控制,增加手术机会。     

华蟾素注射液联合全身化疗治疗中晚期乳腺癌的临床效果分析

目的:探讨华蟾素注射液联合全身化疗治疗中晚期乳腺癌的临床疗效及安全性。方法:选择我科收治的81例中晚期乳腺癌患者并将其随机分为两组,联合组(40例)采用华蟾素注射液联合全身化疗给予治疗,化疗组(41例)单纯给予化疗治疗。治疗后3个月,评价和比较两组的近期和远期疗效,生活质量的改善情况以及不良反应的发生情况。结果:治疗后3个月,联合组治疗有效率明显高于化疗组(P0.05)。截至目前,联合组平均生存期为15个月,化疗组为10个月,两组差异没有统计学意义(P0.05)。联合组的生活质量提高率明显高于化疗组(P0.05)。骨髓抑制和胃肠道反应为两组主要的不良反应,联合组胃肠道反应的发生率明显低于化疗组(P0.05)。结论:华蟾素联合全身化疗对中晚期乳腺癌具有较好的近期治疗效果,并能改善患者的生活质量,且毒副反应较少。     

Thymidylate Synthetase as a Chemotherapeutic Target in the Treatment of Avian Coccidiosis*

SYNOPSIS. Thymidylate synthetase (E.C.2.1.1.45) has been demonstrated in unsporulated oocysts of Eimeria tenella. The properties of this enzyme have also been investigated in Tetrahymena pyriformis, as a protozoan model, and 7-day-old chick embryo, as a host model. The enzymes from E. tenella and chick embryo were inhibited by all concentrations of MnCl₂ and MgCl₂ tested. Tetrahymena pyriformis thymidylate synthetase was stimulated by low concentrations of both these cations but was inhibited by high concentrations. Subsequent data refer to chick embryo, E. tenella and T. pyriformis respectively: the apparent K_m was 5.89 μM, 5.94 μM, and 0.53 M for the substrate dUMP: and 5.13 μM, 1.10 μM and 4.65 μM, respectively for the cofactor N⁵N¹⁰-methylenetetrahydrofolate. The pH optimum for the enzyme from both chick embryo and T. pyriformis was 8.0, with Tris-HCl buffer; activity of E. tenella thymidylate synthetase was still increasing at pH 8.2. The E. tenella enzyme was found to have a molecular weight of 4.6–4.9 × 10⁵ daltons. The effects of nucleotides, inhibitors, and the omission of assay components on each enzyme are presented. Thymidylate synthetase from E. tenella is not greatly different from that of chick embryo, but does not resemble the enzyme from T. pyriformis. A case for using thymidylate synthetase as a chemotherapeutic target in the treatment of Eimeria infections remains. Indeed Eimeria may be considered as a model for infections caused by other protozoan parasites, such as Toxoplasma and Plasmodium, provided that suitable inhibitors can be found that are not toxic to the host.     

D1 in G2

No Abstract Available

Key Words

D-type Cyclins, Cyclin D1, Ras