常规化疗药物疗效预测分子与化疗选药

选择化疗药物是决定化疗效果的关键,是化疗中最困难的治疗决定,如何选择目前没有定论。我们提出常规化疗药物疗效预测分子靶向化疗,即根据个体肿瘤组织的常规化疗药物疗效预测分子(predictivemolecule)表达情况选择临床常规化疗药物,选择预测相对敏感的药物,避开预测相对耐药的药物。例如,对于p53高表达肿瘤可以选择预测相对敏感的紫杉醇类药物,而对于P-gp高表达肿瘤尽量避免使用预测相对耐药的紫杉醇。本文综述p53、P-gp、拓扑异构酶-1、拓扑异构酶-2、MSI、BRCA-1、ERCC1、FANC、hMHL1/2、XPD、Bcl-2、ErbB-2、MGMT、DPD、TS、dCK、Ras、BAX、CyclinA、微管蛋白等疗效预测分子对顺铂、奥沙利铂、环磷酰胺、异环磷酰胺、氮烯咪胺、甲氨蝶呤、氟尿嘧啶、吉西他滨、阿霉素、长春新碱、长春瑞宾、紫杉醇、拓扑替康、依诺替康、足叶乙甙等常规化疗药物的疗效预测作用。

肺癌分子靶向化疗后不良反应的个体化护理研究

众所周知,肺癌已成为威胁人类健康的主要疾病,其治疗方法也成为人们所关注的热点之一[1]。传统的化疗和放疗由于缺乏特异性,疗效欠佳。近年来,生物治疗作为继手术、放疗、化疗等传统疗法之外的第四种治疗手段,在肺癌的综合治疗中发挥着日渐重要的作用,并越来越受到人们的重视[2]。口服靶向化疗药物不仅显著延长癌症患者生存期,由于毒副作用小,有效提高了患者的生活质量[3]。

2012年“脑肿瘤化疗及分子靶向治疗学习班”第一轮通知

中山大学肿瘤防治中心在2007年、2008年、2011年成功主办了四期神经肿瘤化疗培训班，经过短期培训学习，学员们对中枢神经系统肿瘤化疗有了新的认识和提高，返回工作单位后在脑肿瘤化疗临床实践中发挥了很大作用。

2013年“脑肿瘤化疗及分子靶向治疗学习班”通知

中山大学肿瘤防治中心在过去的六年成功主办了六期神经肿瘤化疗培训班，经过短期培训学习，学员们对中枢神经系统肿瘤化疗有了新的认识和提高，返回工作单位后在脑肿瘤化疗临床实践中发挥了很大作用。

2011年“脑肿瘤化疗及分子靶向治疗学习班”通知

中山大学肿瘤防治中心在2007年、2008年成功主办了三期神经肿瘤化疗培训班,经过短期培训学习,学员们对中枢神经系统肿瘤化疗有了新的认识和提高,返回工作单位后在脑肿瘤化疗临床实践中发挥了很大作用。

卵巢癌的基因治疗

卵巢癌的发生是多基因参与的过程 ,随着对癌基因、抑癌基因的深入研究 ,提出基因治疗是癌症治疗的最新策略 .卵巢癌基因治疗的方法包括突变补偿、分子化疗、基因免疫治疗等措施 ,基因治疗将为临床治疗卵巢癌提供新的途径 .

肿瘤基因治疗新策略

本文综述了有关肿瘤基因治疗的新策略,主要有突变补偿、分子化疗及遗传性免疫增强等方法。突变补偿是指去除激活的癌基因或增强抑癌基因的表达;分子化疗是将毒素基因释放到肿瘤细胞中而达到化疗“辐射”作用;遗传性免疫增强法是通过导入免疫刺激分子或肿瘤相关抗原基因而增强宿主对肿瘤的免疫反应。这些方法发展迅速,日趋成熟,为恶性肿瘤的基因治疗带来新的曙光。

肿瘤细胞线粒体靶向表达Dm-dNK基因的实验研究

目的:探讨线粒体基质内核苷酸类似物的磷酸化水平,及Dm-dNK作为新的自杀基因杀伤肿瘤细胞的效果。方法:克隆线粒体信号于Dm-dNK序列N端,与绿色荧光蛋白(GFP)形成融合蛋白以确定基因的亚细胞水平表达位点,构建质粒转染骨肉瘤细胞及胰腺癌细胞,测定转染细胞Dm-dNK的活性和其对于嘌呤核苷酸类似物araC、dFdC、BVDU及araT的细胞毒性。结果:在所测试的细胞株中,线粒体基质内表达Dm-dNK具有较高的酶活性,转染肿瘤细胞对araC、araT及dFdC的敏感性增加。结论:Dm-dNK可以定位表达于肿瘤细胞线粒体并保持酶的活性,可能成为肿瘤基因治疗新的靶向作用位点。

肺癌脑转移诊治策略进展

随着肺部原发病灶治疗手段的日趋完善，脑转移病灶的治疗成为临床研究的热点。目前对脑转移瘤治疗仍存在着一些争议，尚未形成标准的诊治规范。主要是几个关键因素缺乏可比性，如系统疾病的病程阶段、神经损害症状的程度、转移灶数目和部位、瘤细胞类型或原发灶对放疗的敏感性以及不同治疗方式的组合在临床治疗时有时难以选择等。

Tesmilifene获美国快通道地位

YM Biosciences公司的领先产品tesmilfene（I）已获得美国快通道评估地位，与蒽环类合用治疗晚期乳腺癌。该公司仍在寻求阐明信中的某些方面，但说它确实证明，（I）作为小分子化疗增强剂，达到转移性／复发性乳腺癌快通道要求的标准。（I）现正在作一项有700例快速进展的转移性及复发性乳腺癌妇女的Ⅲ期试验，比较（I）＋表柔比星／环磷酰胺与单用表柔比星／环磷酰胺治疗效果，YM公司也与Sanofi—Aventis公司合作，在同样的人群中，作（I）与Taxotere（多西他赛）联合治疗的Ⅱ期试验。（I）已转让给韩国的Shin Poong Pharmaceutical公司，用于胃癌。

Molecular therapy for hepatic injury and fibrosis:Where are we?

Hepatic fibrosis is a wound healing response, involving pathways of inflammation and fibrogenesis. In response to various insults, such as alcohol, ischemia, viral agents, and medications or hepatotoxins, hepatocyte damage will cause the release of cytokines and other soluble factors by Kupffer cells and other cell types in the liver. These factors lead to activation of hepatic stellate cells, which synthesize large amounts of extracellular matrix components. With chronic injury and fibrosis, liver architecture and metabolism are disrupted, eventually manifesting as cirrhosis and its complications. In addition to eliminating etiology, such as antiviral therapy and pharmacological intervention, it is encouraging that novel strategies are being developed to directly address hepatic injury and fibrosis at the subcellular and molecular levels. With improvement in understanding these mechanisms and pathways, key steps in injury, signaling, activation, and gene expression are being targeted by molecular modalities and other molecular or gene therapy approaches. This article intends to provide an update in terms of the current status of molecular therapy for hepatic injury and fibrosis and how far we are from clinical utilization of these new therapeutic modalities.

晚期原发性肝癌药物治疗研究进展

肝癌是临床常见的恶性肿瘤之一,在全球最常见恶性肿瘤中居第六位,在肿瘤相关致死率中占第三位。由于多数肝癌患者确诊时已是晚期,且对于晚期原发性肝癌缺乏有效的治疗措施,肝癌的治疗仍然是临床一大难题。临床上放射性治疗和肝移植手术等只对早期肝癌有效,对于晚期原发性肝癌的治疗多采用全身系统性治疗,主要包括分子靶向药物治疗、化疗等,其中索拉非尼是晚期肝癌药物治疗的金标准。本文对晚期原发性肝癌药物治疗最新进展作一综述。

Effect of Prometheus liver assist system on systemic hemodynamics in patients with cirrhosis: A randomized controlled study

AIM： To evaluate treatment safety and hemodynamic changes during a single 6-h treatment with the PrometheusTM liver assist system in a randomized, controlled study. METHODS： Twenty-four patients were randomized to either the study group or to one of two control groups： Fractionated Plasma Separation Adsorption and Dialysis, PrometheusTM system （Study group; n = 8）; Molecular Adsorbent Recirculation System （MARS）TM （Control group 1, n = 8）; or hemodialysis （Control group 2; n = 8）. All patients included in the study had decompensated cirrhosis at the time of the inclusion into the study. Circulatory changes were monitored with a Swan-Ganz catheter and bilirubin and creatinine were monitored as measures of protein-bound and water-soluble toxins. RESULTS： Systemic hemodynamics did not differ between treatment and control groups apart from an increase in arterial pressure in the MARS group （P = 0.008）. No adverse effects were observed in any of the groups. Creatinine levels significantly decreased in the MARS group （P = 0.03） and hemodialysis group （P = 0.04）. Platelet count deceased in the Prometheus group （P = 0.04）.CONCLUSION： Extra-corporal liver support with Prometheus is proven to be safe in patients with endstage liver disease but does not exert the beneficial effects on arterial pressure as seen in the MARS group,

The “predictive molecule targeted chemotherapy” for relapsed ovarian cancer—a pilot study

Objective: How to choose chemotherapy regimen is a often-encountered and formidable problem in the setting of relapsed ovarian cancer. So far, it was usually according to the clinical trials and doctors’ experience and the response rate was very low. In the present study, we proposed a new treatment strategy–the “predictive molecule targeted chemotherapy, PMTC” to choose supposedly sensitive protocols and void supposedly resistant protocols based on the specific predictive molecule expression of individual tumor tissue. Methods: Retrospectively analysis of 16 cases of relapsed ovarian cancer patients from January 2002 to December 2003, as the experience-directed chemotherapy group (control group), to calculate the response rate. Prospectively recruit 9 cases of relapsed ovarian cancer patients after January 2004, whose chemotherapy drug choice was based on the expression of 6 predictive molecules (p53, et al) by means of immunohistochemistry, as the PMTC group, to calculate the response rate. χ2 test was used for the statistical analysis. Results: The response rate of control group was 26%, including 31% for second line and 14% for third line respectively. The response rate of PMTC group was 78%, in which 5 cases of early relapse all responded. The difference was significant (P=0.011). Conclusions: PMTC is a new effective method to treat the relapsed ovarian cancer.

非小细胞肺癌基因检测指导下的个体化治疗疗效分析

目的:探讨核苷酸切除修复交叉互补基因1(Excision Repair Cross Complementation l,ERCC 1)和核苷酸还原酶亚单位M 1(Subunit M l of Ribonucleotide reductase,RRM 1)分子标志物指导下的化疗药物选择在晚期NSCLC病人治疗中的有效性及安全性。方法:68例III或IV期NSCLC病人采用免疫组织化学方法检测分子标志物的蛋白表达。将晚期NSCLC病人分为分子标志物指导治疗组(A组)及对照组(B组)。A组用分子检测方法检测ERCC 1、RRM 1分子标志物,并根据检测结果确定化疗方案。B组为未经分子标志物检测的经验治疗组。经过化疗后,观察两组的疗效、无进展生存期(progressive-free survival,PFS)、总生存期(overall survival,OS)及化疗过程中的不良反应。结果:基于分子标志物检测指导下选用的化疗方案比经验性化疗方案的有效率明显提高(χ2=5.707,P=0.017),PFS明显延长(P=0.04),差异有统计学意义;两组OS无显著性差异;不良反应无明显差异。结论:分子标志物指导下的化疗方案能够提高化疗有效率,显著延长疾病无进展生存时间。吉西他滨+顺铂方案在分子标志物指导药物选择的策略下应用,将取得更高的治疗缓解率。

Functionalized Gold Nanorods for Tumor Imaging and Targeted Therapy

Gold nanorods,as an emerging noble metal nanomaterial with unique properties,have become the new exciting focus of theoretical and experimental studies in the past few years.The structure and function of gold nanorods,especially their biocompatibility, optical property,and photothermal effects,have been attracting more and more attention.Gold nanorods exhibit great potential in applications such as tumor molecular imaging and photothermal therapy.In this article,we review some of the main advances made over the past few years in the application of gold nanorods in surface functionalization,molecular imaging,and photothermal therapy. We also explore other prospective applications and discuss the corresponding concepts,issues,approaches,and challenges,with the aim of stimulating broader interest in gold nanorod-based nanotechnology and improving its practical application.

Different response to neoadjuvant chemotherapy for different molecular subtypes in patients with locally advanced breast cancer

Objective： The aim of this study was to evaluate the impact of different molecular subtypes defined by immunohistochemistry （IHC） staining on the response rate for patients with locally advanced breast cancer received neoadjuvant chemotherapy. Methods： One hundred and seven breast cancer patients admitted from 2007 to 2011 who received 4 cycles of docetaxel/epirubicin-combined （TE） neoadjuvant chemotherapy were retrospectively reviewed, the patients were classified into 4 subtypes： luminal A, luminal B, HER-2 and triple negative breast cancer （TNBC） according to different combination patterns of estrogen receptor （ER）, progesterone receptor （PR） and human epidermal growth factor-2 （HER-2） expression defined by IHC method. The correlation between response rate and the molecular subtypes were analyzed. Results： The pathological complete response （PCR）, clinical complete response （CCR）, clinical partial response （CPR）, and clinical stable disease （CSD） rate of whole group was 15.89% （17/107）, 22.43% （24/107）, 63.55% （68/107）, 14.02% （15/107）, respectively, and the overall response rate （ORR） was 85.98% （92/107）. The PCR rate and ORR of luminal A, luminal B, HER-2 and TNBC subtypes was 4.76% and 73.81%; 16.67% and 83.33%;17.65% and 100.00%; 30.00% and 96.67%, respectively. The PCR and ORR rate of HER-2/TNBC subtypes was higher than that of luminal A/B subtypes （P = 0.019, P = 0.002, respectively）. Conclusion： Different molecular subtypes display different response rate for patients with locally advanced breast cancer received neoadjuvant TE chemotherapy, HER-2JTNBC subtypes have a higher PCR and ORR rate than that of luminal NB subtypes.

Rectal cancer treatment: improving the picture

Multidisciplinary approach for rectal cancer treatment is currently well defined. Nevertheless, new and promising advances are enriching the portrait. Since the US NIH Consensus in the early 90's some new characters have been added. A bird's-eye view along the last decade shows the main milestones in the development of rectal cancer treatment protocols. New drugs, in combination with radiotherapy are being tested to increase response and tumor control outcomes. However, therapeutic intensity is often associated with toxicity. Thus, innovative strategies are needed to create a better-balanced therapeutic ratio. Molecular targeted therapies and improved technology for delivering radiotherapy respond to the need for accuracy and precision in rectal cancer treatment.

Biliary tract tumors: past, present and future

Tumors ofthe biliary tract （gallbladder tumors, cholangiocarcinomas and ampullary carcinomas） are low incidence tumors with poor prognosis. The five-year overall survival is 50% for stage I, 30% stage II, 10% stage III and 0% stage IV. Treatment is based on surgery for potentially resectable tumors. Chemotherapy and chemo-radiotherapy is the treatment of choice when surgery is not amenable, however it has not achieved encouraging results. These patients use to have very few symptoms, which is the reason for the delay in diagnosis and the poor prognosis. They frequently develop biliary obstruction： obstructive jaundice, right upper quadrant pain and weight loss. Ampullary carcinomas are frequently related to steatorrhea due to malabsorption. The most effective chemotherapy drugs used in monotherapy are 5FU （response rate 20%） and gemcitabine （response rate of 13%-60%）, so they have been selected for further development in multiple phase II clinical trials to explore their efficacy and safety in combination with other agents. In a phase III clinical trial, combination of gemcitabine and cisplatin has been selected as the schedule of choice. Target therapies are also being developed in this malignancy. The present work reviews the most current knowledge of the pathogenesis, diagnosis and natural history of biliary tract tumors. Further, review of surgery, current adjuvant treatment and therapies for unresectable and advanced disease is provided. The most recent understanding for target therapies and molecular biology is also summarized.

The molecular mechanisms of Yang Wei Kang Liu powder on anticancer and reducing chemotherapy side-effect in combination with chemotherapy

Objective:We studied the molecular mechanisms of Yang Wei Kang Liu Power(YWKL,traditional Chinese medicine for nourishing stomach and anticancer) on anticancer and reducing chemotherapy side-effect in combination with chemotherapy.Methods:615 pre-cancer mouse model of YWKL for 10 days and CTX 1 time,semi-quantitative reverse transcription-polymerase chain reaction(RT-PCR) to detect bone marrow granulocyte-macrophage colony-stimulating factor(GM-CSF) gene and cancer proto-oncogene Bcl-2,c-myc expression.Results:YWKL in combination with chemotherapy could obviously promoted the expression of GM-CSF gene and inhibited the expression of Bcl-2 and c-myc oncogenes of FC 615 mice.Conclusion:The molecular mechanisms of anticancer and reducing chemotherapy side-effect of YWKL in combination with chemotherapy are to promote the expression of GM-CSF gene and inhibit the expression of Bcl-2 and c-myc oncogenes.