化疗损伤性卵巢功能早衰小鼠动物模型的研究

目的探索建立化疗损伤性卵巢功能早衰动物模型的适宜方法及最佳时间。方法以70只ICR雌性小鼠为研究对象,腹腔连续注射顺铂7~14 d,观察不同剂量和时间条件下顺铂对小鼠的体重、卵巢功能、肝肾毒性及卵巢组织抗氧化系统各指标的变化。结果顺铂可引起小鼠体重明显下降,卵巢功能减退,出现肝肾毒性,并可引起卵巢抗氧化及氧化损伤指标的异常,与对照组比较均有明显差异。结论3.0~4.0 mg/(kg.bw)的顺铂作用7 d后即可引起小鼠出现明显的卵巢功能衰退、肝肾损伤,氧化损伤是顺铂产生其毒性作用的可能机制之一。该模型的生殖内分泌和病理组织学变化,与人类化疗损伤性卵巢功能早衰病变过程相似。     

P-糖蛋白对结肠癌多药耐药的影响

结肠癌是常见的消化道恶性肿瘤。对术后患者以及无法采用手术治疗的患者,临床多采用化疗、放疗等综合性治疗方法。随着大量化疗药物在临床的广泛使用,结肠癌多药耐药性成为化疗失败的最主要原因。研究表明,P-糖蛋白(P-glycoprotein, P-gp)作为ATP结合盒(ABC)转运蛋白超家族成员之一,与多种肿瘤的多药耐药相关,其介导的多药耐药已经成为目前研究的热点。本文旨在通过对P-糖蛋白的结构、耐药机制以及逆转P-糖蛋白介导的结肠癌多药耐药新发现进行阐述,引导读者对P-糖蛋白在结肠癌多药耐药中的作用有更深入的了解。     

恶性肿瘤病人股静脉置管化疗的护理

恶性肿瘤病人化疗是综合治疗手段之一,化疗药物多为化学及生物碱制剂。反复穿刺易造成周围静脉炎及渗漏性损伤的发生．给患者带来痛苦．中断化疗,延误治疗。为减少药物性静脉炎,保证化疗的顺利进行,2008年1月～12月我科对80例恶性肿瘤病人采用股静脉置管进行化疗．取得了较好的效果。现将护理体会报告如下。     

青龙胶囊对减轻恶性肿瘤患者放射治疗中皮肤副反应的效果观察（附16例分析）

青龙胶囊对减轻恶性肿瘤患者放射治疗中皮肤副反应的效果观察（附１６例分析）湖北省郧阳地区医院肿瘤科熊奎,李超,裴光兰恶性肿瘤是严重危害人类健康的主要疾病之一,作为治疗的主要方法之一的放射治疗（以下简称放疗）,有时因放射野内皮肤损伤而使治疗暂时中断,放疗...     

恶性肿瘤化疗所致院内感染31例分析

目的探讨恶性肿瘤患者化疗后发生院内感染的相关因素及防治措施。方法对31例恶性肿瘤患者化疗后发生的院内感染作回顾性分析。结果恶性肿瘤患者化疗后发生院内感染与中性粒细胞减少程度及持续时间有关,感染的部位以呼吸道为主,主要采用粒细胞集落刺激因子（G-CSF）及抗生素治疗。结论恶性肿瘤患者化疗所致院内感染与中性粒细胞减少程度及持续时间密切相关,合理使用G—CSF及抗生素是预防和控制感染的重要措施。     

肺癌化疗患者延续护理需求与个性化护理干预研究进展

正肺癌的发病率不断攀升,已跃居恶性肿瘤病死率的首位,成为恶性肿瘤常见的死亡原因之一。近年来,化疗对肺癌的治疗作用越来越大,不仅用于不能手术的晚期肺癌患者,还可作为肺癌的全身综合治疗方法,延长患者生存期,提高生活质量。现就肺癌化疗不良反应、延续护理的现状、个性化护理干预作一综述如下。1肺癌化疗不良反应肺癌是当今世界最常见的恶性肿瘤之一,辅助化疗是晚     

妇科卵巢恶性肿瘤腹腔灌注化疗患者的护理

腹腔灌注化疗已成为治疗妇科肿瘤的有效方法之一。特别是卵巢肿瘤,无论是早期还是晚期,手术治疗后均采用以铂类为基础的腹腔内化疗,增加了肿瘤与药物接触,可减少抗肿瘤药所致的全身不良反应,减轻痛苦,提高恶性肿瘤患者的生存质量和治疗效果。现将我院妇科2009年1月～2010年1月收治的36例卵巢恶性肿瘤患者术后腹腔灌注化疗的护理体会报告如下。     

头颈部肿瘤放疗患者的健康教育

放射治疗是治疗恶性肿瘤的主要手段之一。国内约有70％以上的恶性肿瘤病人需要放射治疗。放射线不仅能抑制和破坏肿瘤细胞导致癌细胞的死亡,对正常的组织细胞也有损伤。由于病人及家属对肿瘤知识的普遍缺乏,对放射治疗知识了解甚少,使病人在放射治疗过程中自我防护意识差,放射反应大,并发症严重而导致放射治疗中断乃至失败。为使头颈部肿瘤放射治疗的患者从身心两方面积极配合治疗,减少并发症的发生,促进康复,我们对放射治疗患者开展了有目的、有针对性的分阶段健康教育。     

肿瘤多药耐药分子机制研究进展

化疗是治疗恶性肿瘤主要方法之一。然而不幸的是,先天或获得性耐药尤其是多药耐药的发生,最终导致化疗失败。因此,深入探讨多药耐药发生的分子机制,寻找可以有效预测肿瘤化疗敏感性的分子标志物以及逆转多药耐药的分子靶点,是提高化疗效果的有效途径。肿瘤多药耐药分子机制错综复杂,本文主要从DNA损伤修复、ABC转运蛋白家族表达和功能异常、肿瘤干细胞、拓扑异构酶活性改变、上皮间质转分化、谷胱甘肽-S-转移酶表达改变、表观遗传学修饰以及缺氧等方面对肿瘤多药耐药分子机制进行阐述。     

肺癌铂类化疗所致周围神经毒性与SNP相关性研究

目前肺癌发病率与死亡率均居恶性肿瘤首位,铂类药物已广泛应用于肺癌等多种癌症的治疗。然而,铂类药物化疗取得较佳疗效的同时,往往由于严重的毒副反应而限制了其使用剂量,从而难以达到最佳疗效。其中,铂类药物化疗所引起的周围神经毒性(peripheral neurotoxicity,PN)十分常见。与此同时,临床中周围神经毒性的发生存在较大的个体性差异,其药物代谢相关基因的单核苷酸多态性(single nucleotide polymorphism,SNP)的遗传变异可能是引起PN发生个体差异的重要原因之一。本文就DNA修复酶、药物代谢酶、转运体等相关基因的SNP与铂类化疗引起的PN之间的相关性作一综述。     

细胞凋亡抑制蛋白cIAP 与卵巢癌耐药性的研究进展

卵巢恶性肿瘤是女性生殖系统三大恶性肿瘤之一,其发病率在女性生殖系统肿瘤中占第三位,而死亡率却高居首位。目前对于晚期卵巢癌(Ⅲ或Ⅳ期)多倾向于用新辅助化疗+肿瘤细胞减灭术+术后周期性化疗的治疗方法。但是,尽管多数患者在最初对化疗药物较敏感,但仍有60%~80%最终死于卵巢癌,这些患者大部分都对化疗药物产生了耐药性,在更换新的化疗方案初期是有效的,但最终仍会耐药。近年来,有关细胞凋亡抑制蛋白(cIAP,cellular inhibitors of apoptosis proteins)在卵巢癌复发耐药中的作用机制的研究越来越受到重视。研究证实,cIAP在耐药肿瘤细胞中呈高表达,并与多种因子共同参与形成了上皮性卵巢癌的耐药机制,抑制了化疗药物引起的肿瘤细胞的凋亡。这些发现为攻克卵巢癌的耐药机制提供了重要线索,也为卵巢癌化疗药物的应用指出了新的方向。     

New frontiers in ovarian cancer diagnosis and management.

Ovarian carcinoma is now the leading cause of death among women. Surgery has reached its limits, and further aggressive surgery will result in an inordinate morbidity and mortality. Ovarian carcinoma is ideally treated by complete surgical removal of the cancer, followed by anti-cancer chemotherapy. Since it is often impossible to remove all of the cancer, adjunctive chemotherapy is playing an increasingly important role in the management of the cancer. New anti-cancer drugs must be found or synthesized, and new combinations of current anti-cancer drugs with mechanisms to protect the bone marrow must be explored. The field of genetics and the identification of the patient at high risk because of a familial history of ovarian cancer must be expanded. The role of tumor markers and oncogenes requires more in-depth study so that these signs can play a greater role in monitoring and identifying the patient with early ovarian cancer. The emerging fields of genetic engineering and biologic response modifiers are opening up new avenues for additional modalities of therapy. The expanding areas of research in cancer are starting to dispel the doom and gloom of the last three decades with a spirit of optimism for the diagnosis and treatment of ovarian cancer, as the new century approaches.     

Chemotherapeutic drugs induced female reproductive toxicity and treatment strategies

Increase in success of cancer treatment with advancement in the screening, prognosis and diagnosis protocols have significantly improved the rate of cancer survivorship. With the declining cancer mortality, however, the cancer survivors are also subjected to the adverse consequences of chemotherapy, particularly in the female reproductive system. Recent studies have shown the sensitivity of the ovarian tissue to the chemotherapeutic drugs-induced toxicity. Several in vitro and in vivo studies have assessed the toxic effects of chemotherapeutic drugs. The most frequently used chemotherapeutic drugs such as doxorubicin, cyclophosphamide, cisplatin and paclitaxel have been reported to cause ovarian damage, diminution of follicular pool reserve, premature ovarian failure and early menopause, resulting into declining fertility potential among females. The chemotherapy often employs combination of drug regimen to increase the efficacy of the treatment. However, the literature mostly consists of clinical data regarding the gonadotoxicity caused by anticancer drugs but there lacks the understanding of toxicity mechanism. Therefore, understanding of the different toxicity mechanisms will be helpful in development of possible therapeutic interventions for preservation of declining female fertility among cancer survivors. The current review comprehends the underlying mechanisms of female reproductive toxicity induced by the most commonly used chemotherapeutic drugs. In addition, the review also summarizes the recent findings related to the use of various protectants to diminish or at least in managing the toxicity induced by different chemotherapeutic drugs in females.     

Quantitative immunoproteomics analysis reveals novel MHC class I presented peptides in cisplatin-resistant ovarian cancer cells

Platinum-based chemotherapy is widely used to treat various cancers including ovarian cancer. However, the mortality rate for patients with ovarian cancer is extremely high, largely due to chemo-resistant progression in patients who respond initially to platinum based chemotherapy. Immunotherapy strategies, including antigen specific vaccines, are being tested to treat drug resistant ovarian cancer with variable results. The identification of drug resistant specific tumor antigens would potentially provide significant improvement in effectiveness when combined with current and emerging therapies. In this study, using an immunoproteomics method based on iTRAQ technology and an LC-MS platform, we identified 952 MHC class I presented peptides. Quantitative analysis of the iTRAQ labeled MHC peptides revealed that cisplatin-resistant ovarian cancer cells display increased levels of MHC peptides derived from proteins that are implicated in many important cancer pathways. In addition, selected differentially presented epitope specific CTL recognize cisplatin-resistant ovarian cancer cells significantly better than the sensitive cells. These over-presented, drug resistance specific MHC class I associated peptide antigens could be potential targets for the development of immunotherapeutic strategies for the treatment of ovarian cancer including the drug resistant phenotype.     

BRCA1 epigenetic inactivation predicts sensitivity to platinum-based chemotherapy in breast and ovarian cancer

Germline mutations in the BRCA1 or BRCA2 genes are associated with an increased risk of breast and ovarian cancer development. Both genes are involved in DNA repair, and tumors harboring genetic defects in them are thought to be more sensitive to DNA-damaging agents used in chemotherapy. However, as only a minority of breast and ovarian cancer patients carry BRCA1 or BRCA2 mutations, few patients are likely to benefit from these pharmacogenetic biomarkers. Herein, we show that, in cancer cell lines and xenografted tumors, BRCA1 CpG island promoter hypermethylation-associated silencing also predicts enhanced sensitivity to platinum-derived drugs to the same extent as BRCA1 mutations. Most importantly, BRCA1 hypermethylation proves to be a predictor of longer time to relapse and improved overall survival in ovarian cancer patients undergoing chemotherapy with cisplatin.     

BRCA1 epigenetic inactivation predicts sensitivity to platinum-based chemotherapy in breast and ovarian cancer

Germline mutations in the BRCA1 or BRCA2 genes are associated with an increased risk of breast and ovarian cancer development. Both genes are involved in DNA repair, and tumors harboring genetic defects in them are thought to be more sensitive to DNA-damaging agents used in chemotherapy. However, as only a minority of breast and ovarian cancer patients carry BRCA1 or BRCA2 mutations, few patients are likely to benefit from these pharmacogenetic biomarkers. Herein, we show that, in cancer cell lines and xenografted tumors, BRCA1 CpG island promoter hypermethylation-associated silencing also predicts enhanced sensitivity to platinum-derived drugs to the same extent as BRCA1 mutations. Most importantly, BRCA1 hypermethylation proves to be a predictor of longer time to relapse and improved overall survival in ovarian cancer patients undergoing chemotherapy with cisplatin.     

Ovarian cancer stem cell: A potential therapeutic target for overcoming multidrug resistance

The cancer stem cell (CSC) model encompasses an advantageous paradigm that in recent decades provides a better elucidation for many important biological aspects of cancer initiation, progression, metastasis, and, more important, development of multidrug resistance (MDR). Such several other hematological malignancies and solid tumors and the identification and isolation of ovarian cancer stem cells (OV-CSCs) show that ovarian cancer also follows this hierarchical model. Gaining a better insight into CSC-mediated resistance holds promise for improving current ovarian cancer therapies and prolonging the survival of recurrent ovarian cancer patients in the future. Therefore, in this review, we will discuss some important mechanisms by which CSCs can escape chemotherapy, and then review the recent and growing body of evidence that supports the contribution of CSCs to MDR in ovarian cancer.     

Disruption of protein neddylation with MLN4924 attenuates paclitaxel-induced apoptosis and microtubule polymerization in ovarian cancer cells

Surgery and chemotherapy are the gold-standard treatments for ovarian cancer. The major cause of treatment failure in patients with ovarian cancer is tumoral heterogeneity and drug resistance. Paclitaxel (PTX) is one of the most commonly used first-line drugs for ovarian cancer chemotherapy. Unfortunately, the mechanisms of PTX chemoresistance remain unclear. Here, we examined the effects of post-translational neddylation on the sensitivity of ovarian cancer cells (OCCs) to PTX-induced apoptosis. Disruption of protein neddylation with the first-in-class inhibitor MLN4924 dramatically neutralized PTX-mediated antiproliferative, antimigration, and apoptotic effects in human OCCs. Moreover, MLN4924 treatment interrupted PTX-induced microtubule polymerization. Importantly, two neddylation conjugating E2 enzymes, UBE2M and UBE2F, were found to play essential roles in PTX-induced cytotoxicity and tubulin polymerization in OCCs. In summary, our findings demonstrated that disruption of protein neddylation by MLN4924 conferred resistance to PTX and provided insights into the potential mechanisms of PTX chemoresistance in ovarian cancer.     

卵巢癌的靶向药物治疗研究进展

卵巢癌死亡率居女性生殖系统恶性肿瘤之首,早期诊断困难,晚期患者治疗效果差,分子靶向药物成为近年的研究热点。目前许多靶向药物已经进入临床试验阶段,给卵巢癌特别是术后复发及化疗耐药患者的治疗带来新的希望。本文主要对单克隆抗体,酪氨酸激酶抑制剂等几种药物在卵巢癌的研究进行综述。