105例恶性肿瘤患者首次化疗后心电图变化

近年来恶性肿瘤的缘台治疗中，化疔占有重要的位置。不同的化疗药物和方案在产生治疗效果的同时．也出现不少毒副作用。单一药物和剂量对心脏毒性已报道不少，本文采用不同化疗方案对105倒恶性肿瘤患者治疗前后心电图变化进行观察，意在探索联台方案对初治病人的心脏毒性。     

RRM1和ERCC-1与非小细胞肺癌化疗耐药的研究进展

非小细胞肺癌（NSCLC）是一种易产生化疗耐药的肿瘤，预后差。目前临床上常根据经验和患者的经济情况选择化疗方案，然而，在化疗方案与给药剂量相同的情况下，不同个体对化疗的敏感性有很大的差异，这种差异使传统依靠经验进行化疗面临极大的挑战。因此迫切需要一种能够预测化疗疗效的方法。为患者进行个体化治疗提供依据，以提高化疗效果，延长生存时间．本文综述了参与核苷酸切除修补途径的重要基因ERCC-1和RRM1及其与NSCLC化疗疗效相关性的研究进展。     

胸苷酸合成酶基因多态性与消化道肿瘤个体化治疗

消化道肿瘤的发生率在我国位居第一，而多数患者确诊时即为中晚期，已失去手术的机会，故化疗已成为此类患者的主要治疗手段。虽然以氟尿嘧啶（5-Fu）为基础的联合化疗可以延长胃癌、结直肠癌等晚期消化道肿瘤的生存期，但是接受此类方案中至少50％患者对化疗无效，而且同一化疗方案对不同患者的疗效可从完全缓解到无效，产生差别的主要原因在于个体间对化疗药物敏感性不同所致，近年来的各项研究逐渐表明，TS基因的多态性与患者对化疗药物的敏感性密切相关。     

剂量密集化疗方案在乳腺癌中的应用

自20世纪70年代以来,关于乳腺癌化疗的研究报道逐渐增多[1],各国学者们不断探索,通过不同药物间的组合、改变给药顺序、增加药物剂量、延长或缩短给药时间等方式,力求使更多患者从化疗中获益.剂量密集方案是指单次用药剂量不变的情况下,缩短每次化疗之间的时间间隔,以期获得更好的治疗效果.本文就剂量密集方案在乳腺癌治疗方面的进展综述如下.     

院内鼻咽癌患者营养管理的研究进展

摘 要：鼻咽癌因其特殊的解剖结构和对放疗的敏感性，决定了放疗为其首选的治疗方式。随着肿瘤治疗方案的多样化，化疗药物也日益丰富。由于放化疗的影响，患者出现摄食困难等症状，随着放疗剂量的累积效应，进而发生营养不良，影响治疗效果和预后。全文综述鼻咽癌放化疗患者院内营养管理的现状、营养管理的具体内容，以及在实施过程中的影响因素，旨在规范临床医务人员对鼻咽癌患者的营养管理，为进一步丰富管理策略提供参考依据。     

化疗剂量对肿瘤化疗后衔接生物治疗的影响

目的：探讨化疗剂量对肿瘤化疗后衔接生物治疗的影响。为实施肿瘤化疗 生物治疗联合方案时选择化疗剂量提供依据。方法：以丝裂霉素C（MMC）注射小鼠，确定高低2种不同剂量；采用pCH510质粒转染，Hep70-肿瘤抗原肽复合物注射，制裁粒转染 复合物注射3种不同生物治疗方式衔接不同药物剂量的化疗，对H22肝癌细胞接种的小鼠进行治疗，对疗效进行比较。结果：通过MMC的毒性试验确定了100μg为高剂量，50μg为低剂量，肿瘤化疗后衔接不同方式的生物治疗，均可提高疗效，但高剂量化疗后衔接生物治疗的效果更佳。在低剂量化疗后，给予3种不同生物治疗，它们之间的疗效并没有差别，而在高剂量化疗后，3种不同的生物治疗方式的疗效则出现了显著差异。化疗后同时进行pCH510质粒转染 Hsp70-肿瘤抗原肽复合物免疫注射，效果最好。结论：不同的化疗剂量对肿瘤化疗之后进行的生物治疗会产生的影响。在高剂量化疗下，生物治疗和化疗两者联合可以更好地提高疗效。     

探讨接受BSA指导用药剂量的乳腺癌化疗患者个体间多西他赛药代动力学差异

目的:探索乳腺癌患者接受体表面积（BSA）指导用药剂量的多西他赛(DTX)化疗后患者体内药代动力学多态性,以揭示患者体内药物暴露的差异。方法:采用纳米增强免疫比浊法测定258例患者血浆中的DTX浓度,计算每位患者的关键药代动力学参数AUC,并进行DTX药物浓度监测。结果:258例患者个体间的AUC值分布在0.40~2.67 mg·h/L,变异系数40.6%。采用不同化疗方案的各组患者的AUC并未显示出显著的差异,<50岁以及50~70岁组患者的AUC显著低于>70岁组患者的AUC(P=0.007,P=0.012)。结论:采用BSA指导用药剂量的DTX化疗可导致个体患者间的疗效和毒副作用出现巨大差异,需优化现有的用药剂量制定方案以提高乳腺癌患者尤其是老年乳腺癌患者（>70岁）DTX药物有效性并降低毒副作用。     

多西紫杉醇药物浓度-时间曲线下面积给药方式在乳腺癌患者中的应用

多西紫杉醇是一种半合成的紫杉烷类抗肿瘤药物。其通过抗微管作用抑制细胞分裂增殖,达到抑制肿瘤的目的,因此,在各期乳腺癌中均有较广泛的应用。由于其血液学不良反应大,临床上个体间用药剂量差异明显,甚至出现不规范用药现象。为了使用更高的药物剂量去获得患者的最大耐受,使患者得到以最佳治疗效果和最小不良反应为目的的精准治疗,笔者对多西紫杉醇的药代动力学及其与化疗不良反应的关系,以及依据体表面积和依据药物浓度-时间曲线下面积给药方式的相关研究进展作一综述,以期为临床上合理调节用药量提供参考。     

TECIA法体外放射敏感性实验对原发性肺鳞癌放疗个体化方案选择的意义

目的：建立人原发性肺鳞癌的组织培养放疗敏感性检测法,快速确定人原发性肺鳞癌组织的辐射敏感性的个体差异,用于筛选放疗方案及指导临床肿瘤个体化放疗方案。方法：采用TECIA法检测不同个体原发性肺鳞癌组织在不同剂量、不同分次放疗方案照射后不同时间的细胞凋亡水平。比较不同剂量、不同分次放疗方案照射后不同时间的细胞凋亡水平的差异。结果：TECIA法发现,照射前人原发性肺鳞癌组织细胞凋亡指数较低,放疗后出现较高的细胞凋亡指数,与放疗剂量呈正相关。结论：肿瘤放射敏感性实验对指导患者的个体化治疗具有重要的价值。     

大剂量化疗联合自体骨髓或造血干细胞移植治疗恶性脑胶质瘤研究进展

恶性脑胶质瘤治疗困难，死亡率高。近十年来发展的大剂量化疗联合外周造血干细胞移植治疗恶性脑胶质瘤取得了一些疗效，特别对髓母细胞瘤、原发性神经外胚层肿瘤和高级别的星型细胞瘤有较好的效果。目前所用的治疗方案，大部分是单一的大剂量双氯乙基亚硝脲的治疗方案(800—1000mg／m2)，另有一些多药组合方案，但大剂量方案引起了较多的不良反应，而并未显著提高患者的平均生存时间，故仍需新的药物和方案进行临床试验。     

Cancer chemotherapy of high-age patients with gastrointestinal malignancies

Recently, high aged patients with malignancies have increased in number. When cancer chemotherapy is applied for the high aged patients, kinds or doses of anti-cancer drugs must be more carefully selected or decided than for younger patients, because it is said that the side effects of anti-cancer drugs would easily induce irreversible organ disorders and death in high aged patients. The effects of cancer chemotherapy were compared between high aged patients (over 75 years) and younger patients (5 decade years) with special reference to side effects. The patients underwent cancer chemotherapy were 79.7% of high aged patients and 93.6% of younger. The reasons why cancer chemotherapy was not carried out were high age (5.6% of high aged patients), poor general conditions (7.0% in high aged, 2.3% in younger) and post operative complications (7.0% in high aged, 3.2% in younger). The proportion of patients suffered side effects was almost same in both groups. Dead cases caused by side effects of anti-cancer drugs were 5 in high aged patients (4.4%) and 7 in younger (3.4%). The reason why the proportion of side effects in both groups was not different was that the doses of anti-cancer drugs given for high aged patients were reduced to 80-90% of those for younger patients.     

Retinoids as anti-cancer agents and their mechanisms of action

Retinoids (vitamin A) have been reported extensively for anti-cancer properties due to their high receptor-binding affinities and gene regulation abilities. However, the anti-cancer potential of retinoids has not been reviewed in recent years. Thus, this review focused on the anti-cancer effects of retinoids and their synergistic effects with other drugs, together with their mechanisms of action in different types of cancers reported in the past five years. The retinoids were well studied in breast cancer, melanoma, and colorectal cancer. Synthetic retinoids have shown higher selectivity, stronger effectiveness, and lower toxicity than endogenous retinoids. Interestingly, the combination treatment of endogenous retinoids with chemotherapy drugs showed enhanced anti-cancer effects. The mechanisms of action reported for retinoids mainly involved the RAR/RXR signaling pathway. However, limited clinical studies were conducted in recent years. Thus, retinoids which are highly potential anti-cancer agents are worth further study in clinical, especially as a combination therapy with chemotherapy drugs.     

Oncobiguanides: Paracelsus' law and nonconventional routes for administering diabetobiguanides for cancer treatment

“The dose makes the poison”, the common motto of toxicology first expressed by Paracelsus more than 400 years ago, may effectively serve to guide potential applications for metformin and related biguanides in oncology. While Paracelsus'' law for the dose-response effect has been commonly exploited for the use of some anti-cancer drugs at lower doses in non-neoplastic diseases (e.g., methotrexate), the opposite scenario also holds true; in other words, higher doses of non-oncology drugs, such as anti-diabetic biguanides, might exert direct anti-neoplastic effects. Here, we propose that, as for any drug, there is a dose range for biguanides that is without any effect, one corresponding to “diabetobiguanides” with a pharmacological effect (e.g., insulin sensitization in type 2 diabetes, prevention of insulin-dependent carcinogenesis, indirect inhibition of insulin and growth factor-dependent cancer growth) but with minimal toxicity and another corresponding to “oncobiguanides” with pharmacological (i.e., direct and strong anticancer activity against cancer cells) as well as toxic effects. Considering that biguanides demonstrate a better safety profile than most oncology drugs in current use, we should contemplate the possibility of administering biguanides through non-conventional routes (e.g., inhaled for carcinomas of the lung, topical for skin cancers, intravenous as an adjunctive therapy, rectal suppositories for rectal cancer) to unambiguously investigate the therapeutic value of high-dose transient biguanide exposure in cancer. Perhaps then, the oncobiguanides, as we call them here, could be viewed as a mechanistically different type of anti-cancer drugs employed at doses notably higher than those used chronically when functioning as diabetobiguanides.     

Clinical trial of chemotherapy identified according to chemosensitivity assay for oral cancer patients with unresectable recurrent lesions

Treatment of patients with unresectable recurrent oral cancer is quite difficult. In particular,there is no scientific evidence to select anti-cancer drugs for patients who were given previous radiation therapy. To select optional chemotherapy regimens, we have employed a new chemosensitivity testing method, a collagen gel droplet embedded culture sensitivity test (CD-DST) for patients with unresectable oral cancer. Six oral cancer patients with recurrence and/or metastatic disease were treated with the optional chemotherapy based on the results of CD-DST. No result was obtained due to a problem of poor growth of tumor cells in one case. In another case, we could not find a sensitive anti-cancer drug among the agents we examined. These 2 patients were treated with selected palliative pain control therapy. Optional chemotherapy based on the results of CD-DST was given to 4 patients showing sensitivity to the anti-cancer drugs examined. Tumor recession or tumor dormancy was observed clinically during a definite period. Toxicity was mild and the median survival was 10.9 months. We therefore conclude that the examination with CD-DST may provide important scientific evidence to determine a suitable chemotherapy for patients with advanced oral cancer.     

Methodological aspects of the 6-day subrenal capsule assay for measuring the response of human tumors to anticancer agents

Methodological aspects of testing chemosensitivity by the 6-day subrenal capsule (SRC) assay in immunocompetent mice were investigated. Human tumor xenografts, serially transplanted in athymic nude mice, were used as source of material. All drugs were given by the intravenous route. Administration of the drugs on days 1 and 2 gave the same results as when they were given daily for 5 days in equitoxic total doses, and a clear dose-response relationship was demonstrated. High reproducibility was found with different anti-cancer agents when 15 different tumors (4 melanomas, 7 soft tissue sarcomas, 2 colon carcinomas, and 2 lung carcinomas) were tested repeatedly over a period of several years. The tumors examined showed individual chemosensitivity profiles. The same ranking of drugs was found when the results in the SRC assay were compared with those obtained in the sc nude mouse model, using the same tumors (a colon carcinoma and a leiomyosarcoma), supporting the validity of the SRC assay. Altogether, the results strongly support the view that the 6-day SRC assay in immunocompetent mice is a useful method for assessing the response of human tumors to anticancer agents.     

The differences of standard therapy for breast cancer between Europe/America and Japan--chemotherapy, operation,and radiotherapy

As increased incidence of breast cancer, the concept of standard therapy based on the evidence based medicine (EBM) has been widely applied to breast cancer treatment in Japan. Since the major parts of evidences are common in Western countries and Japan,general treatment strategy for standard care seems to be identical in both countries. However, there are still some differences due to the limited usages of anti-cancer drugs and supporting drugs. We would discuss about these issues in this paper.     

Growth Hormone Receptor Knockdown Sensitizes Human Melanoma Cells to Chemotherapy by Attenuating Expression of ABC Drug Efflux Pumps

Melanoma remains one of the most therapy-resistant forms of human cancer despite recent introductions of highly efficacious targeted therapies. The intrinsic therapy resistance of human melanoma is largely due to abundant expression of a repertoire of xenobiotic efflux pumps of the ATP-binding cassette (ABC) transporter family. Here, we report that GH action is a key mediator of chemotherapeutic resistance in human melanoma cells. We investigated multiple ABC efflux pumps (ABCB1, ABCB5, ABCB8, ABCC1, ABCC2, ABCG1, and ABCG2) reportedly associated with melanoma drug resistance in different human melanoma cells and tested the efficacy of five different anti-cancer compounds (cisplatin, doxorubicin, oridonin, paclitaxel, vemurafenib) with decreased GH action. We found that GH treatment of human melanoma cells upregulates expression of multiple ABC transporters and increases the EC50 of melanoma drug vemurafenib. Also, vemurafenib-resistant melanoma cells had upregulated levels of GH receptor (GHR) expression as well as ABC efflux pumps. GHR knockdown (KD) using siRNA in human melanoma cells treated with sub-EC50 doses of anti-tumor compounds resulted in significantly increased drug retention, decreased cell proliferation and increased drug efficacy, compared to mock-transfected controls. Our set of findings identify an unknown mechanism of GH regulation in mediating melanoma drug resistance and validates GHR as a unique therapeutic target for sensitizing highly therapy-resistant human melanoma cells to lower doses of anti-cancer drugs.     

Anti-Diabetic Drugs: Cure or Risk Factors for Cancer?

Anti-diabetic drugs are an important group of therapeutics used worldwide. Different anti-diabetic drugs lower blood glucose level by different mechanisms. In recent years, numerous investigations have been performed based on both comparative and cohort studies, in order to establish the relationship between anti-diabetic pharmacotherapy and cancer incidence as well as mortality due to cancer. Some anti-diabetic drugs have been found to exhibit anti-cancer activity while others might increase the risk for cancer. The underlying cause for this disparity is likely to be the varying mechanisms of action of these drugs in controlling blood glucose level. This review discusses the various carcinogenic and/or anti-cancer effects of commonly used anti-diabetic drugs. The information is vital in view of the fact that diabetes mellitus is a commonly occurring disease with a rising incidence rate.     

Membrane cholesterol content and sensitivity of human carcinoma-cells to antineoplastic ether phospholipids

Ether phospholipids represent a new class of anti-cancer drugs which appear to exert their tumoricidal activity through a direct and indirect cytotoxic effect against tumor cells of different origins. The chemotherapeutic interest in these new drugs is based on the finding that, contrary to the majority of anti-cancer drugs, ether phospholipids do not interfere with DNA synthesis, are anti-invasive and induce tumor cell differentiation. There is increasing experimental evidence that the direct cytotoxic effect of these new drugs is mediated by the cell membrane. We have measured the lipid membrane composition of three human carcinoma cell lines that have been found to possess different sensitivity to the tumoricidal activity of four antitumor ether phospholipids. A statistically significant difference has been found in the membrane cholesterol content of the three cell lines and a positive correlation has been established between the membrane cholesterol level and the carcinoma cell sensitivity to ether phospholipids. These findings emphasize previous data obtained with leukemic cells and reinforce the interest in ether phospholipids whose cytotoxic properties may represent a new step towards a more promising anti-cancer chemotherapy.     

Recent development of oral anti-cancer drugs for breast cancer

Oral anti-cancer drugs play an important role in the treatment of breast cancer. Because these hormonal agents are related to mammary carcinogenesis and tumor growth, they are used not only for therapy but also to prevent the onset of the disease. Tamoxifen, toremifene, fadrozole and other aromatase inhibitors, goserelin, leuprolin and MPA are used widely in Japan as hormonal anti-cancer drugs. In addition oral anti-cancer chemotherapeutic agents, such as cyclophosphamide, 5-FU, 5'-DFUR, FT and UFT are used for breast cancer. The combination of these hormonal and chemotherapeutic agents produces good clinical results in curing the disease. Oral drugs are superior to injected drugs with regard to the QOL of patients.