甘草抗肿瘤作用研究进展

近年来,中医药在恶性肿瘤的治疗中发挥重要作用。甘草是最常用的中药之一,主要活性成分为三萜皂苷类、黄酮类以及香豆素类物质。研究发现,甘草可通过介导肿瘤细胞凋亡和自噬、抑制肿瘤细胞增殖和转移等途径发挥抗肿瘤作用。目前,甘草相关方剂,如大黄甘草汤、补中益气汤和六君子汤等,在肿瘤辅助治疗中多有应用,可缓解肿瘤疼痛、黏膜刺激、胃肠道不良反应、贫血等。针对甘草抗肿瘤的主要有效成分异甘草素水溶性差、生物利用度低、体内半衰期短的问题,纳米悬浮液、脂质-聚合物杂化纳米颗粒系统和聚合物胶束等新型药物递送系统的研究突飞猛进。开发甘草及其生物活性成分作为抗肿瘤药物具有巨大潜力和应用价值。     

纳米金用于肿瘤免疫治疗的研究进展

摘 要：肿瘤免疫疗法作为一种高效高安全性的抗肿瘤策略,主要通过激活人体免疫系统发挥抗肿瘤效应。多种纳米材料在肿瘤免疫治疗研究中被用于免疫佐剂和疫苗的肿瘤靶向递送。该文主要综述了纳米金作为免疫药物和药物载体在抗肿瘤研究中的应用。纳米金不仅能通过自身的独特优势发挥免疫调节作用,还能够特异性地在体内将免疫制剂运送至效应部位,降低药物的不良反应,提升了免疫药物的作用效果,保障了免疫疗法的安全实施,为肿瘤治疗提供了新思路和新策略。     

基于纳米材料的刺激响应策略在肿瘤治疗中的研究进展

化疗作为肿瘤主要的治疗方法具有靶向性差、不良反应严重等缺点。随着纳米医学的不断发展，研究发现基于纳米材料的刺激响应策略可以通过肿瘤微环境的pH、氧化还原、ROS和酶等响应条件以及外部的光、磁等响应条件促进化疗药物在肿瘤内的聚集、摄取和释放，从而提高药物的安全性和杀伤效果。本文综述了常见的基于纳米材料的刺激响应策略及其在肿瘤治疗中的作用，为其在临床应用以及未来的研究发展提供一定参考。     

多肽介导的给药系统在肝癌靶向治疗中的研究进展

摘 要：肝癌是常见的恶性肿瘤,也是癌症相关死亡的重要原因之一。多肽具有尺寸小、合成修饰容易、免疫原性低等优点。因此,多肽修饰的靶向给药系统近年来引起研究者们越来越多的关注。多肽介导的纳米药物传递系统( 脂质体、聚合物胶束和纳米粒等)能有效地将药物传递至肝癌细胞,提高肿瘤部位的药物浓度从而增强药物疗效,减少不良反应。多肽介导的靶向药物传递系统在肝癌靶向治疗中发挥着重要作用。全文就近5年来多肽介导的给药系统在肝癌靶向治疗中的应用研究进展做一简要综述,以期为肝癌靶向制剂的研发提供参考。     

透明质酸-紫杉醇纳米制剂在肿瘤治疗中的研究进展

紫杉醇是目前最有效的抗癌药物之一,但由于它的水溶性、药代动力学和体内分布性能较差,且其增溶剂对人体有很强的毒副作用,限制了它的临床应用.为了提高紫杉醇的水溶性、渗透率及稳定性,研究人员制备出一种具有缓释作用、可控及肿瘤靶向的药物——透明质酸-紫杉醇纳米制剂.以透明质酸为载体的纳米载药系统可以降低紫杉醇的毒副作用,利用合适的给药途径将透明质酸-紫杉醇纳米制剂输送至体内,提高了药物的靶向性、水溶性及长循环能力,使药物通过扩散、包吞或受体介导的内吞作用进入细胞.文章综述了透明质酸-紫杉醇纳米制剂在多种恶性肿瘤中的应用.     

基于肿瘤微环境的基因给药纳米载体的研究进展

近年来基因给药系统在肿瘤治疗中的研究备受关注。纳米载体具有增强药物靶向性、增加生物膜通透性、控制药物释放速度、提高生物利用度和可承载生物大分子等优点。由于肿瘤的快速增殖和代谢,形成了具有低pH、高水平谷胱甘肽、高水平活性氧、缺氧性、高表达酶和高水平ATP等特性的肿瘤微环境（TME）。基于肿瘤组织特异性微环境的基因给药纳米载体能同时提高基因药物的胞外稳定性、胞内释放能力和靶向性,可更大程度地提高药物的抗肿瘤作用、减少不良反应的发生。本文对基于TME的pH响应型、还原响应型、活性氧响应型、缺氧响应型、酶响应型、ATP响应型和多智能响应型纳米载体进行综述,总结各类型纳米载体的作用机制、制备、抗肿瘤效果及局限性。基因给药纳米载体可提高基因的转染效率,提高抗肿瘤作用,在抗肿瘤应用中有较好的前景。     

肿瘤穿透肽iRGD在肿瘤靶向纳米递药治疗中的研究进展

恶性肿瘤是目前严重威胁人类生命健康的重大疾病之一,随着对恶性肿瘤研究的深入,越来越多的抗肿瘤药物被研发应用并取得显著的成效,但是由于复杂的肿瘤微环境,抗肿瘤药物常难以渗透至肿瘤组织深部,导致生物利用度低,抗肿瘤作用减弱。肿瘤穿透肽（tumor-penetrating peptide）iRGD化学连接在纳米载体表面或者与纳米载体联合给药,促进药物渗透至肿瘤组织深部有效发挥抗肿瘤作用,是目前肿瘤靶向治疗领域中备受关注的研究方向之一。本文回顾并总结了iRGD在抗肿瘤靶向纳米递药治疗中的研究进展,这些研究结果都显示了肿瘤穿透肽iRGD在肿瘤靶向治疗中拥有良好的应用前景。     

中国医学科学院肿瘤医院肿瘤新型纳米药物研发项目首获国家重点研发计划支持

临床肿瘤治疗揭示：高效、低毒和可控的化疗药物是肿瘤药物治疗的重大需求，研发新型纳米药物是肿瘤临床需求导向的首要任务。中国医学科学院肿瘤医院分子肿瘤学国家重点实验室马洁研究员作为项目负责人，联合北京化工大学、上海交通大学以及中国医学科学院医药生物技术研究所共同申报的“临床需求导向的肿瘤新型纳米药物研发”项目获国家重点研发计划“纳米科技”重点专项批准，这是我国肿瘤纳米药物领域获批的首个国家重点研发计划项目。该项目将以精简纳米药物组分为主导思想，研究具有原创性和实用性的纳米药物及纳米技术改性的新剂型，揭示纳米药物胞内转运和体内递送的过程与规律以及体内外作用的分子机制，实现为肿瘤病人提供更多药物选择的目标。     

载5-氟尿嘧啶两亲多糖纳米粒的制备及其对肝癌细胞HepG2的杀伤作用

背景与目的:生物可降解载药纳米微粒作为新型药物靶向传输和缓释/控释载体,可延长药物的生物半衰期,减轻药物的毒副作用,而且具有良好的生物相容性。本实验制备可生物降解的载5-氟尿嘧啶(5-fluorouracil,5-FU)葡聚糖接枝聚乳酸共聚物(5-FU/DEX-g-PLA),探讨其对人肝癌细胞HepG2的体内外杀伤作用。方法:利用分子自组装技术制备5-FU/DEX-g-PLA载药纳米微粒,透射电镜观察纳米粒形态,分光光度法计算载药率,MTT法观察对HepG2细胞的体外杀伤作用,动物实验观察其体内抑瘤效应。结果:5-FU/DEX-g-PLA纳米微粒呈球形,粒径约50nm,药物包封率约9.3%。体内药物代谢动力学数据显示,5-FU纳米制剂在血液中维持时间长于5-FU裸药;MTT结果显示,5-FU纳米组细胞生长抑制率(58.8%)与5-FU裸药组(58.0%)差异无显著性(P>0.05);体内抑瘤实验显示,5-FU纳米组肿瘤抑制率(73.1%)显著高于5-FU裸药组(57.5%)。结论:5-FU/DEX-g-PLA纳米微粒可有效抑制肝癌细胞的生长。     

脂质体阿霉素在肿瘤热化疗中的研究进展

体内外研究表明，脂质体阿霉素在肿瘤热化疗研究方面，联合热疗疗效明显优于单独热疗或单药脂质体阿霉素治疗，其作用机制可能是热疗直接引起阿霉素从脂质体中释放，增加加热区域肿瘤组织的微循环渗透压，从而增加了肿瘤细胞对药物的生物利用度，发挥协同增加抗肿瘤作用。临床研究表明，联合热化疗在难治性或复发的卵巢癌、晚期乳腺癌、恶性软组织肉瘤及肝癌等晚期恶性肿瘤疗效较好。     

Bacteria and cancer--antagonisms and benefits

There is considerable historical and recent evidence concerning the antagonisms between acute bacterial infections or their toxins and cancer and allied diseases. These data provide renewed incentives to undertake clinical programmes with mixed bacterial vaccines in many countries at the present time.     

Salivary and serum proteomics in head and neck carcinomas: before and after surgery and radiotherapy

Several body fluids have been evaluated as new sources for cancer biomarker discovery. In this context, salivary and serum proteomics seem promising diagnostic and predictive tools for head and neck diseases. In the present study, we performed a proteomic analysis of saliva and serum from patients presenting head and neck squamous cell carcinoma (HNSCC) and compared the results before and after therapy. In saliva of cancer patients, we observed an altered protein profile, including over-expression of PLUNC and zinc-alpha-2-glycoprotein. Both proteins may contribute to control tumor growth and, therefore, represent targets for new analysis. We also detected serotransferrin and a modified transthyretin form with altered levels in serum from patients. Comparing preoperative and postreatment samples, the results showed that the protein profile after treatment reverted to a pattern closer to those observed for controls. These results add information on the role of secreted proteins in the cancer process and emphasize the potential of saliva and serum analysis for diagnosis and monitoring of HNSCC.     

Proliferation and apoptosis in acute and chronic leukemias and myelodysplastic syndrome

Clonal expansion of leukemic cells is thought to be due to proliferation in excess of apoptosis. To define and compare proliferation and apoptosis between various leukemias and myelodysplastic syndrome (MDS), we measured proliferating cell nuclear antigen (PCNA) and bromodeoxyuridine (BrdU) incorporation as surrogate markers for proliferation and caspase 3 activity and annexin V surface binding as surrogate markers for activation of the apoptotic cascade in patients with MDS, chronic myelomonocytic leukemia (CMML), acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), and chronic myeloid leukemia (CML). We found high proliferation in bone marrow cells from MDS and CMML as measured by PCNA and BrdU incorporation. The lowest level of proliferation was found in CLL. Apoptosis was also highest in MDS and CMML as measured by annexin V and caspase 3 activity. Unexpectedly, we found no significant difference in proliferation in bone marrow CD34+ cells from various leukemias or MDS. Apoptosis was significantly higher in bone marrow CD34+ cells from MDS and CML in chronic phase as compared to CD34+ cells from AML patients. Our results illustrate differences in proliferation and apoptosis between acute and chronic leukemias and MDS. These differences may have diagnostic and therapeutic implications.     

Occupational and environmental radiation and cancer

Epidemiologic evidence on the relation between occupational and environmental radiation and cancer is reviewed. Studies of pioneering radiation workers, underground miners, and radium dial painters revealed excess cancer deaths and contributed to the setting of radiation protection standards and to theories of carcinogenesis. Occupational exposures today are generally much lower than in the past, thus any associated increases in cancer will be difficult to detect. Pooling investigations of these more recently exposed workers, however, has the potential to validate current estimates of risk used in radiation protection. New information on the effects of chronic radiation exposure also may come from studies in the former Soviet Union of Chernobyl clean-up workers and of workers at the Mayak nuclear facilities. Studies of environmental radiation exposures, other than radon, are largely inconclusive, due mainly to the difficulties in detecting the low risks associated with low dose exposures. Thyroid cancer, however, has been linked to environmental radiation from the Chernobyl accident and from nuclear weapons tests. Low-level radiation released during normal operations at nuclear plants has not been found to increase cancer rates in surrounding populations. Radon, a human carcinogen, is the most ubiquitous exposure to human populations; remediating high residential-radon levels is recommended, recognizing that the exposure can never be removed completely because it occurs naturally.     

Religiosity and Physical and Emotional Functioning Among African American and White Colorectal and Lung Cancer Patients

The literature suggests that religiosity helps cope with illness. The present study examined the role of religiosity in functioning among African Americans and Whites with a cancer diagnosis. Patients were recruited from an existing study and mailed a religiosity survey. Participants (N = 269; 36% African American, 56% women) completed the mail survey, and interview data from the larger cohort was utilized in the analysis. Multivariate analyses indicated that in the overall sample religious behaviors were marginally and positively associated with mental health and negatively with depressive symptoms. Among women, religious behaviors were positively associated with mental health and negatively with depressive symptoms. Religiosity was not a predictor of study outcomes for men. Among African Americans, religious behaviors were positively associated with mental health and vitality. Among Whites, religious behaviors were negatively associated with depressive symptoms. These findings suggest a mixed role of religious involvement in cancer outcomes. The current findings may have applied potential in the areas of emotional functioning and depression.     

Genetic polymorphisms of alcohol and aldehyde dehydrogenases and risk for esophageal and head and neck cancers

Alcoholic beverages are causally related to cancer of the oral cavity, pharynx, larynx and esophagus. Ethanol is oxidized to acetaldehyde and then to acetate by alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), both of which have genetic polymorphisms. A review of case-control studies of the effects of ALDH2, ADH2 and ADH3 genotypes shows consistently positive associations between inactive heterozygous ALDH2 and the less-active ADH2 genotypes and the risk for esophageal cancer in East Asian heavy drinkers and this enzyme-related vulnerability may extend to light-to-moderate drinkers. Some studies suggest similar associations with the risk for head and neck cancer in moderate-to-heavy-drinking Japanese. An established carcinogen in experimental animals, acetaldehyde can interact with human DNA. ALDH2-associated cancer susceptibility fits into a scenario in which acetaldehyde plays a critical role in the development of human cancer. Alcohol flushing and drinking behavior may partly explain this carcinogenic effect in carriers of less-active ADH2 genotypes. Whether the ADH3 genotype influences head and neck cancer risk in Western nations is controversial. Professional and public education about risky conditions connected to the ALDH2 and ADH2 genotypes and environmental factors is important in a new strategic approach to the prevention of alcohol-related cancers in East Asians. The use of simple tests to identify inactive ALDH2 on the basis of alcohol flushing responses could benefit many people, by helping them to identify their own cancer risks. Such testing could also help clinicians diagnose esophageal cancer earlier, through the use of endoscopic screening in the high-risk population.