应用ATP-生物荧光法筛选鼻咽癌化疗药物

目的探讨ATP-生物荧光法肿瘤化疗药敏试验在鼻咽癌化疗药物筛选中的应用价值。方法采用ATP-生物荧光法和MTT法分别对人鼻咽低分化鳞癌细胞株(CNE-2)进行12种化疗药物的肿瘤化疗药敏试验。结果 ATP-TCA法与MTT法所求得作用于CNE-2细胞的IC_(50)比较,其差异在统计学上无意义(P>0.05)。ATP-TCA法检测CNE-2对12种化疗药物的敏感性依次为:顺铂(DDP)、丝裂霉素(MMC)、紫杉醇(TXL)、长春瑞宾(NVB)、卡铂(KB)、羟基喜树碱(HCT)、五氟尿嘧啶(5-FU)、长春新碱(VCR)、更生霉素(ACTD)、鬼臼碱(Vp-16)、吡柔比星(THP)、表阿霉素(EPI)。结论认为ATP肿瘤体外药敏试验(ATP-TCA)应用于鼻咽癌化疗药物的筛选,具有敏感、快速、与临床相关性较好的特点,是目前最有发展前途的体外药敏试验方法;DDP和TXL合用可提高对CNE-2肿瘤细胞的抑制率。

抗肿瘤药所致不良反应的防治与合理应用原则

伴随着生态环境、遗传基因、生活和精神因素的改变，肿瘤尤其是恶性肿瘤的发病率与病死率逐年攀升。抗肿瘤药通过破坏肿瘤细胞的生长周期、转录、功能、环境和结构，或抑制肿瘤组织内的新生血管、营养物质合成，抑制肿瘤细胞生长或杀灭肿瘤细胞，达到对抗和治疗肿瘤的目的。在化疗中，其在破坏和杀伤肿瘤细胞的同时，给正常组织和细胞也带来了风险。周期非特异性抗肿瘤药对恶性肿瘤细胞的作用较强且快，高浓度下能迅速杀灭恶性肿瘤细胞，剂量／疗效反应曲线接近于直线，在人体能耐受的毒性限度内，其杀伤能力随剂量的增加而增加，在浓度和时限的关系中，浓度是主要因素。周期特异性抗肿瘤药的剂量／疗效反应曲线是一条渐近线，即在小剂量时类似于直线，达到一定剂量后不再上升，出现稳定平台，相对而言，在影响疗效的浓度与时间的关系中，时间是主要的因素。因此，为使抗肿瘤化疗药发挥最大作用，非特异性药宜静脉一次注射，而特异性药则以缓慢静脉滴注、肌内注射或口服给药为宜。此外，肿瘤的病因、发病机制、临床症状及患者的身体状况均十分复杂，单药治疗效果并不理想，需要合理地、有计划地联合应用多种治疗手段。

黄芪注射液对人类小涎腺腺样囊性癌细胞株的抑制作用

目的研究黄芪注射液对人类小涎腺腺样囊性癌(NACC)细胞株的抑制作用。方法以不同浓度的黄芪作用于NACC细胞,应用三磷酸腺苷肿瘤化疗药敏试验(ATPTCA)法测定黄芪注射液对NACC细胞的体外增殖抑制作用;应用PI细胞染色法在流式细胞仪上测定细胞凋亡。结果研究发现作用48h后,黄芪浓度为0.065g·mL-1时已对体外培养的细胞株有抑制作用,NACC抑制率达8%,可高度诱导NACC细胞的凋亡。经黄芪作用的癌细胞在显微镜下表现为细胞稀疏、收缩,胞质拉长。HE染色可见明显的细胞内空泡和细胞出泡等凋亡形态学变化现象。结论黄芪注射液能抑制NACC细胞株增殖并诱导细胞凋亡,有较好的抗癌作用。

HPLC法测定人血浆中环磷酰胺的浓度

目的 建立一种可靠、便捷的高效液相色谱法测定人血浆中环磷酰胺 (CTX)浓度的方法。方法 以异环磷酰胺 (Ifo)为内标 ,采用惠普 1 1 0 0型高效液相色谱仪 ,分析柱HPLichrosphereC8柱 (2 50mm× 4mm ,5μm) ,前加HPLicrosphere保护柱 ;流动相为 :乙腈∶水 =1 8∶82 (V/V) ,流速为 1 .5mL/min ;检测波长为 1 95nm ;室温2 5℃。血浆样品以甲醇沉淀蛋白。结果 色谱峰分离良好 ,无干扰。线性方程为 :Y =4.861X +0 .1 81 7,r =0 .9999;线性范围 :0 .5～ 50 μg/mL ;检测限 :0 .1 μg/mL。 结论 本法是一种可靠、便捷的检测血浆CTX浓度的方法 。

表阿霉素诱导血管通透性改变的机制

目的:观察乳腺癌常规化疗药物表阿霉素(EPI)对血管内皮细胞通透性的影响,探讨其在静脉注射时造成血管渗漏的机制。方法:用0、0.1、1.0、10、100μg/mlEPI处理人脐静脉内皮细胞株HUVEC-CRL-1730,光学显微镜观察细胞形态改变,Transwell小室检测单层内皮细胞的通透性,MTT法检测细胞增殖效率,RT-PCR和Western blotting检测血管扩张刺激磷蛋白(VASP)mRNA和蛋白表达水平。结果:10μg/mlEPI处理内皮细胞24h后,与对照组相比,EPI能显著抑制内皮细胞增殖(P<0.05),细胞收缩、变形,单层内皮细胞通透性增加(P<0.05);同时,VASP mRNA和蛋白表达水平均降低(P<0.05)。结论:EPI静脉注射造成的血管渗漏可能与EPI抑制细胞增殖以及通过降低VASP蛋白表达导致的内皮细胞通透性增加有关。

以细胞存亡调控蛋白c-FLIP为靶点的癌症治疗研究

肿瘤细胞通过表达抗凋亡蛋白从而对细胞的凋亡产生耐受,这是肿瘤抗凋亡的重要调节机制。c-FLIP是抗凋亡的主要抑制因子,在人类细胞中,c-FLIP主要有3种亚型,分别为c-FLIPL、c-FLIPS、c-FLIPR。c-FLIP通过与FADD结合,从而影响了procaspase-8-DISC的形成及随后的caspase级联反应。此外,c-FLIPL和c-FLIPS在不同的信号途径中具有多种功能,可以同时上调许多具有细胞保护作用的信号。研究表明,c-FLIP在许多肿瘤细胞中都有所上调,但可以通过不同的化学治疗药物,如调控细胞转录水平的药物曲古抑菌素A、喜树碱、顺铂、阿霉素等传统化疗药或者通过一些最新的生物技术,如siRNA技术,使得c-FLIP表达水平有所下调,以此来恢复肿瘤细胞对凋亡的敏感性。因此,c-FLIP有望作为癌症治疗的重要靶点。该文主要对c-FLIP为靶点的化学治疗药物和siRNA技术等进行综述,并提出新的思路,以期找到特异性抑制或拮抗c-FLIP的抗凋亡效应的小分子化合物。

Cytochrome P450 Directed Prodrug Activation Therapy in Research of Cancer Enzymology

Cancer enzymology is a promising filiation of bio-medical sciences. In thepast decades, enzymes, such as GST(glutathione S-transferase) , PKC(protein kinase C) , Topo(DNAtopoisomerases), TK(tyrosine kinase), CD (bacterial cytosine deaminase), CPG2(carboxypeptidase G2) ,and PNP (purine nucleoside phosphorylase), have been known to bear close relations to cancer. Theirspecific expression and influence on the process of tumor initiation, promotion and progressionattract scientists to apply them as a biochemical marker of certain malignant tumor, a predictor ofresponse in cancer chemotherapy; to apply them to drug design, tumor prevention and as adjuvant toradiotherapy or surgery.

Current endoscopic approach to indeterminate biliary strictures

Biliary strictures are considered indeterminate when basic work-up, including transabdominal imaging and endoscopic retrograde cholangiopancreatography with routine cytologic brushing, are non-diagnostic. Indeterminate biliary strictures can easily be mischaracterized which may dramatically affect patient's outcome. Early and accurate diagnosis of malignancy impacts not only a patient's candidacy for surgery, but also potential timely targeted chemotherapies. A significant portion of patients with indeterminate biliary strictures have benign disease and accurate diagnosis is, thus, paramount to avoid unnecessary surgery. Current sampling strategies have suboptimal accuracy for the diagnosis of malignancy. Emerging data on other diagnostic modalities, such as ancillary cytology techniques, single operator cholangioscopy, and endoscopic ultrasonography-guided fine needle aspiration, revealed promising results with much improved sensitivity.

117 cases of advanced malignancies treated with recombinant human endostatin plus chemotherapy

Objective: The aim of this study was to evaluate the recent efficacy and adverse reactions of recombinant human endostatin (Endostar) plus chemotherapy in the treatment of advanced malignancies. Methods: One hundred and seventeen cases of advanced malignancies were diagnosed and confirmed by histopathological examination, patients were treated with Endostar combined with chemotherapeutic drugs with no cross-resistance. Evaluate the efficacy and adverse reactions after finished two cycles of combination therapy. Results: All the 117 cases of patients were evaluated according to relevant standards, and there were 12 cases of complete remission (CR), 30 cases of partial remission (PR), 58 cases of stable disease (SD), 17 cases of progressive disease (PD). The response rate (RR) was 35.8%, disease control rate (DCR) was 85.4%. Conclusion: The protocol of Endostar combined with chemotherapy could improve the quality of life of patients with malignances, it also has the advantage of low toxicity. Considering the time span of the study, the long-term efficacy remains to be observed.

SENSITIZATION OF ACNU KILLING EFFECTS ON HeLa S3 CELLS BY MGMT ANTI SENSERNA TRANSFECTION

O6 -methylguanine- DNA- methyltransferase (MGMT ) plays a very important role in the cellular resis- tance to nitrosoureas drugs. Inhibition of MGMT might be a useful approach in tumor chemotherapy. In this study, the depletion of MGMT activity by retroviral-mediated antisense RNA transfection were reported. Three retroviral vectors expressing MGMT antisense RNA were constructed and transfected into HeLa S3 cells. The difference of MGMT mRNA, MGMT activity as well as cellular resistance to ACNU before and after transfection were observed. It was found that antisense RNA targeting 5’region and whole length of MGMT mRNA could partially deplete MGMT activity and enhance killing effects of ACNU. However, 3’ region antisense RNA had no effect on MGMT modulation.

Primary hepatic leiomyosarcoma with liver metastasis of rectal cancer

Primary hepatic leiomyosarcoma is a particularly rare tumor with a poor prognosis. Curative resection is currently the only effective treatment, and the efficacy of chemotherapy is unclear. This represents the first case report of a patient with primary hepatic leiomyosarcoma co-existing with metastatic liver carcinoma. We present a 59-year-old man who was diagnosed preoperatively with rectal cancer with multiple liver metastases. He underwent a curative hepatectomy after a series of chemotherapy regimens with modified FOLFOX6 consisting of 5-fluorouracil, leucovorin and oxaliplatin plus bevacizumab, FOLFIRI consisting of 5-fluorouracil, leucovorin and irinotecan plus bevacizumab, and irinotecan plus cetuximab. One of the liver tumors showed a different response to chemotherapy and was diag-nosed as a leiomyosarcoma following histopathological examination. This case suggests that irinotecan has the potential to inhibit the growth of hepatic leiomyosarcomas. The possibility of comorbid different histological types of tumors should be suspected when considering the treatment of multiple liver tumors.

Systemic chemotherapy for hepatocellular carcinoma in non-cirrhotic liver:A retrospective study

AIM:To investigate the efficacy and toxicity of systemic chemotherapy in a retrospective study of patients with hepatocellular carcinoma(HCC)occurring in normal or fibrotic liver without cirrhosis. METHODS:Twenty-four patients with metastatic or locally advanced HCC in a normal or a fibrotic liver were given systemic chemotherapy(epirubicin,cis- platin and 5-fluorouracil or epirubicin,cisplatin and capecitabine regimens).Tumor response,time to pro- gression,survival,and toxicity were evaluated. RESULTS:There were 7 women and 17 men,mean age 54±10 years;18 patients had a normal liver and 6 had a fibrotic liver(F1/F2 on biopsy).Mean tumor size was 14 cm,5 patients had portal vein thrombosis and 7 had metastasis.Patients received a median of 4 chemotherapy sessions.Overall tolerance was good. There were 5 partial responses(objective response rate =22%),and tumor control rate was 52%.Second line surgical resection was possible in two patients.Median survival was 11 mo,and 1-and 2-year overall survival rates were 50%±10%and 32%±11%,respectively. CONCLUSION:In patients with HCC in a non-cirrhotic liver,chemotherapy was well tolerated and associated with an objective response rate of 22%,including two patients who underwent secondary surgical resection.

Combined effects of Cantide and chemotherapeutic drugs on inhibition of tumor cells' growth in vitro and in vivo

AIM: To investigate the combination effect of hTERT antisense oligonucleotide 'Cantide' and three chemotherapeutic drugs (cisplatin, 5-fluorouracil (5-FU) and adriamycin (ADM)) on inhibiting the proliferation of HepG2, BGC and A549 cell lines in vitro, and to investigate the efficacy of Cantide used in combination with cisplatin (DDP) in vivo. METHODS: Cantide was transfected into these tumor cells by Lipofectin, and cell growth activity was calculated by microcytotoxicity assay. In vivo study, cells of HepG2 were implanted in Balb/c nude mice for 4 d. Then Cantide, DDP and Cantide+DDP were given intra peritonea Ily for 24 d respectively. The body weights of the tumor-bearing animals and their tumor mass were measured later to assess the effect of combination therapy in the nude mice. To evaluate the interaction of Cantide and these chemotherapeutic drugs, SAS software and Jin Zhengjun method were used. RESULTS: Combination treatments with 0.1μmol/L Cantide reduced the IC50 of DDP, 5-FU and ADM from 1.07, 4.15 and 0.29 μg/mL to 0.25,1.52 and 0.12 μg/mL respectively. The inhibition ability of DDP, 5-FU and ADM respectively in combination with Cantide in these tumor cells was higher than that of these drugs alone (P<0.0001). And synergism (Q≥1.15)was observed at the lower concentration of DDP (≤1μg/mL) and ADM (≤0.1 μg/mL) with combination of Cantide. In vivo, combination treatment with Cantide and DDP produced the greater growth inhibition of human liver carcinoma cells HepG2 in nude mice (0.65±0.19 g tumor) compared with that when only one of these drugs was used (Cantide group: 1.05±0.16 g tumor, P= 0.0009<0.001; DDP group: 1.13±0.09 g tumor, P= 0.0001<0.001). CONCLUSION: These findings indicate that Cantide may enhance therapeutic effectiveness of chemotherapeutic drugs over a wide range of tumor cells in vitro, and the combination use of Cantide and DDP can produce much higher inhibition rates, as compared with when either of these drugs was used only in vivo.

Chemoradiotherapy with twice-weekly administration of low-dose gemcitabine for locally advanced pancreatic cancer

AIM:To evaluate the chemoradiotherapy for locally advanced pancreatic cancer utilizing low dose gemcitabine as a radiation sensitizer administered twice weekly. METHODS: We performed a retrospective analysis of chemoradiotherapy utilizing gemcitabine administered twice weekly at a dose of 40 mg/m2. After that, maintenance systemic chemotherapy with gemcitabine, at a dose of 1000 mg/m2, was administered weekly for 3 wk with 1-wk rest until disease progression or unacceptable toxicity developed. RESULTS: Eighteen patients with locally advanced unresectable pancreatic cancer were enrolled. Three of those patients could not continue with the therapy; one patient had interstitial pneumonia during radiation therapy and two other patients showed liver metastasis or peritoneal metastasis during an early stage of the therapy. The median survival was 15.0 mo and the overall 1-year survival rate was 60%, while the median progression-free survival was 8.0 mo. The subgroup which showed the reduction of tumor development, more than 50% showed a tendency for a better prognosis; however, other parameters including age, gender and performance status did not correlate with survival. The median survival of the groups that died of liver metastasis and peritoneal metastasis were 13.0 mo and 27.7 mo, respectively.CONCLUSION: Chemoradiotherapy with low-dose gemcitabine administered twice weekly could be effective to patients with locally advanced pancreatic cancer; however, patients developing liver metastases had a worse prognosis. Another chemoradiotherapy strategy might be needed for those patients, such as administrating one or two cycles of chemotherapy initially, followed by chemoradiotherapy for the cases with no distant metastases.

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 Effect of Genetic Polymorphism upon Antineoplastic Sensitivity

In clinical practice, patients undergoing chemotherapy display prominent individual differences, adverse reactions and sensitivity to antineoplastic therapy. Those differences are caused by individual genetic polymorphism of related genes. Genetic variation can induce distinct alterations of drug-metabolizing enzymes, drug transporters, drug targets and DNA repair enzymes and thereby influence the ability of the drugs to reach their target sites. This article reviews in detail the potential interactions mentioned above.

Histone modification as a drug resistance driver in brain tumors

Patients with brain tumors,specifically,malignant forms such as glioblastoma,medulloblastoma and ependymoma,exhibit dismal survival rates despite advances in treatment strategies.Chemotherapeutics,the primary adjuvant treatment for human brain tumors following surgery,commonly lack efficacy due to either intrinsic or acquired drug resistance.New treatments targeting epigenetic factors are being explored.Post-translational histone modification provides a critical regulatory platform for processes such as chromosome condensation and segregation,apoptosis,gene transcription,and DNA replication and repair.This work reviews how aberrant histone modifications and alterations in histone-modifying enzymes can drive the acquisition of drug resistance in brain tumors.Elucidating these mechanisms should lead to new treatments for overcoming drug resistance.

常见的肾毒性药物有哪些

肾脏是机体中毒的易感单位，容易受到损害。因此，当肾脏发生病变时，用药应特别慎重，以免加重病情。