抗黑色素瘤天然药物的研究进展

恶性黑色素瘤是一种来源于黑色素细胞的恶性肿瘤,具有转移早、进展快、预后差、死亡率高的特点.近年来,人们更加关注从天然植物中寻找预防和治疗黑色素瘤的新途径,并取得了一定的成果,对有关中药、天然药物在抗黑色素瘤方面的实验研究进行综述.     

恶性黑色素瘤浸润转移相关分子机制研究

目的:探讨MMP-2、MMP-9、TIMP-2、E-cadherin在高、低恶性黑色素瘤中浸润转移中的作用。方法:将临床资料完整的恶性黑色素瘤样本60例,按CK8、CK18染色结果分为高度恶性和低度恶性2组,并进行MMP-2、MMP-9、TIMP-2、E-cadherin免疫组化染色。结果:高度恶性组黑色素瘤MMP-2、TIMP-2的表达高于低度恶性组黑色素瘤的表达,低度恶性组黑色素瘤MMP-9、E-cadherin的表达高于高度恶性组,其中低度恶性组黑色素瘤MMP-9的表达结果同高度恶性组黑色素瘤的表达差别具有统计学意义(P<0.05)。结论:肿瘤浸润转移相关蛋白在不同肿瘤的浸润转移过程中作用各不相同,MMP-2、TIMP-2促进了肿瘤的浸润转移,而MMP-9、E-cadherin抑制肿瘤的转移。     

抗血管新生治疗在血液肿瘤治疗中的应用

血液肿瘤是临床常见的恶性疾病。恶性淋巴瘤、白血病和多发性骨髓瘤都是常见的临床血液肿瘤疾病。抗血管新生治疗是近年来兴起的一种治疗肿瘤的方法,对肿瘤的转移能力和复发具有控制、降低作用。本文主要分析肿瘤微环境,研究抗血管新生治疗常用药物在血液肿瘤临床治疗中的具体应用。     

萝卜硫素在消化系统肿瘤治疗中的机制研究进展

消化系统肿瘤病死率在全球肿瘤中位于前列, 包括手术、化疗和放疗在内的传统治疗方法存在效果差和耐药的缺点。近年来, 萝卜硫素作为一种天然抗肿瘤化合物在消化系统肿瘤中被广泛研究, 可通过促进癌细胞死亡、阻碍癌细胞增殖、抑制癌细胞侵袭和转移、抗血管生成、加强免疫治疗及减弱耐药性等机制来治疗癌症。本文综述了国内外研究机构关于萝卜硫素治疗消化系统肿瘤机制的研究进展, 为消化系统肿瘤的治疗提供新思路。     

三氧化二砷对恶性黑色素瘤A_(375)细胞的增殖抑制作用

目的　研究三氧化二砷 (As2 O3 )对人恶性黑色素瘤A3 75细胞的增殖抑制作用和抗转移作用 ,为砷及其化合物治疗恶性黑色素瘤提供新的理论和实验依据。方法　用MTT比色法测定A3 75细胞活力 ,用免疫组化方法分析nm2 3蛋白的表达。结果　As2 O3 与人恶性黑色素瘤细胞株A3 75细胞生长抑制率之间有明显的浓度依赖关系 ,IC50 为 13 0 5 μmol·L-1,用药组 (As2 O3 浓度为 2 μmol·L-1)A3 75细胞中有nm2 3抗肿瘤转移基因的表达 ,而对照组则没有。结论　As2 O3 对恶性黑色素瘤A3 75细胞的增殖有浓度依赖性抑制作用 ,并可诱导体内产生nm2 3蛋白 ,对抑制肿瘤的转移和复发及判断预后有重要意义     

恶性黑色素瘤内科治疗进展

恶性黑色素瘤是由位于神经嵴黑色素细胞恶变形成,是恶性程度最高的肿瘤之一,容易出现淋巴管及血道转移。恶性黑色素瘤发病率以每年约4％的速度递增。     

天然产物抗肺癌作用及其机制的研究进展

目的 总结天然产物抗肺癌的机制,为候选治疗肺癌新的前瞻性药物提供理论基础。方法 利用肺癌、中药、药理学及其组合等关键词,收集中国知网、万方、维普、PubMed、Science Direct和Web of science等数据库有关天然产物抗肺癌作用研究的文章,并进行总结。结果 中医药治疗肺癌优势明显,具有药理机制新颖、毒性低、不良反应小的特点,可增效减毒、提高患者生活质量。天然产物主要包括黄酮类、生物碱类、多糖类、萜类、皂苷类和酚类,具有抑制肿瘤细胞周期、抑制增殖、诱导凋亡、促进自噬、抑制肿瘤细胞侵袭和转移的作用;天然产物与细胞毒性药物联合使用,可以增强疗效或降低耐药性,延缓肺癌的进展,延长患者的生存时间。结论 中药含有多种黄酮、生物碱、萜及其苷类、多酚和其他可有效对抗肺癌的活性化合物,适合作为治疗肺癌的候选药物。     

程序性死亡分子1抑制剂Pembrolizumab治疗恶性黑色素瘤研究进展

Pembrolizumab是抗程序性死亡分子1(programmed death-1,PD-1)的单克隆抗体,可与PD-1结合,抑制PD-1与其配体结合,从而激发机体的抗肿瘤作用.在多项临床试验中,Pembrolizumab能显著延长黑色素瘤患者的生存期,因而被美国FDA批准用于治疗晚期不可切除或已转移的恶性黑色素瘤.此文对Pembrolizumab治疗恶性黑色素瘤的研究进展做一综述.     

恶性黑色素瘤的细胞免疫治疗研究进展

恶性黑色素瘤是一种恶性程度极高且发病率持续增长的肿瘤,对术后辅助放、化疗不敏感,预后较差。研究发现,恶性黑色素瘤为免疫原性较高的肿瘤,因此,肿瘤生物治疗得到广泛应用,细胞免疫治疗已成为恶性黑色素瘤个体化综合治疗的重要组成部分及研究热点。本文就恶性黑色素瘤的细胞免疫治疗研究进展作一综述。     

天然多酚衍生物抗肿瘤侵袭与转移研究进展

肿瘤侵袭与转移是恶性肿瘤的基本特征，是临床肿瘤患者死亡的最主要原因。肿瘤侵袭与转移过程涉及细胞的脱落、浸润、迁移运行、着床、新生血管生成等过程，作用机制非常复杂，因此，防止肿瘤转移一直是肿瘤治疗的难题。近年来研究发现，许多天然产物具有抗肿瘤侵袭和转移能力，该文对天然多酚类化合物的抗肿瘤侵袭和转移作用的研究进展进行综述。     

Glycyrrhizic acid facilitates anti-tumor immunity by attenuating Tregs and MDSCs: An immunotherapeutic approach

Melanoma is one of the most aggressive malignancies and its treatment remains challenging due to its highly metastatic property and availability of limited effective drugs. In addition, immunosuppresive tumor microenvironment (TME) has been identified as major barrier to evoke anti-tumor response in melanoma. Recent studies revealed that immunosuppressive TME is directly correlated with heightened activations of T regulatory cells (Tregs) and Myeloid derived suppressor cells (MDSCs) functions. In this study, we investigated the anti-cancer effect of a triterpenoid, glycyrrhizic acid (GA) on melanoma. Our study revealed that GA not only exhibited anti-proliferative effects on melanoma cells it significantly restricted progression of melanoma tumor. However, the therapeutic efficacy of GA in impressive regression of tumor was found to be directly correlated with induction of apoptosis and modulation of cytokines from Th2 to Th1 type. To unravel the mechanism of anti-melanoma effect of GA, it has been delineated that GA inhibits pSTAT3 to evade anti-tumor suppressive function of Tregs and MDSCs. Downregulation of FOXP3, GITR and CTLA4 in tumor-infiltrating Tregs and inhibition of Cox2, PGE2 and Arginase 1 in intra-tumoral MDSC were evidenced as some of the key events during therapeutic intervention of GA in melanoma management. Moreover, GA effectively restricted advanced stage solid tumor while used in combination with Mycobacterium indicus pranii, a known immunomodulator, which alone is reported to be ineffective to restrict advanced stage solid tumor. Thus, our findings may open up a novel insight of GA as a promising agent in cancer immunotherapy or adjuvant therapy in future.     

The dual role of autophagy in cancer

Autophagy is a mechanism for the degradation of cytoplasmic material, damaged organelles and aggregate-prone proteins in lysosomes. Recent evidence indicates that autophagy is a tumor suppressor mechanism, which is connected to its role in the clearance of the scaffold protein p62/SQSTM1 and prevention of oxidative stress and genomic instability. However, since autophagy is a survival mechanism, cancer cells can also exploit it to survive nutrient limitation and hypoxia that often occur in solid tumors. Tumor cells can also upregulate autophagy as a response to cancer treatment, and recent studies show that inhibition of autophagy can enhance the killing of tumor cells after treatment. Interestingly, the FK506-binding protein 51 plays a role in the autophagy-linked radiation resistance of malignant melanoma.     

Anti-tumor effect of Coriolus versicolor methanol extract against mouse B16 melanoma cells: in vitro and in vivo study.

Numerous studies have shown immunostimulatory and anti-tumor effects of water and standardized aqueous ethanol extracts derived from the medicinal mushroom, Coriolus versicolor, but the biological activity of methanol extracts has not been examined so far. In the present study we investigated the anti-tumor effect of C. versicolor methanol extract (which contains terpenoids and polyphenols) on B16 mouse melanoma cells both in vitro and in vivo.In vitro treatment of the cells with the methanol extract (25-1600 microg/ml) reduced melanoma cell viability in a dose-dependent manner. Furthermore, in the presence of the methanol extract (200 microg/ml, concentration IC(50)) the proliferation of B16 cells was arrested in the G(0)/G(1) phase of the cell cycle, followed by both apoptotic and secondary necrotic cell death. In vivo methanol extract treatment (i.p. 50 mg/kg, for 14 days) inhibited tumor growth in C57BL/6 mice inoculated with syngeneic B16 tumor cells. Moreover, peritoneal macrophages collected 21 days after tumor implantation from methanol extract-treated animals exerted stronger tumoristatic activity ex vivo than macrophages from control melanoma-bearing mice. Taken together, our results demonstrate that C. versicolor methanol extract exerts pronounced anti-melanoma activity, both directly through antiproliferative and cytotoxic effects on tumor cells and indirectly through promotion of macrophage anti-tumor activity.     

Geldanamycin, radicicol, and chimeric inhibitors of the Hsp90 N-terminal ATP binding site

Natural products have continued to drive the development of new chemotherapeutics and elucidation of new biological targets for the treatment of disease. Since Whitesell and Neckers' original discovery that geldanamycin does not directly inhibit v-Src, but instead manifests its biological activity through inhibition of the Hsp90 molecular chaperone, additional natural products and natural product derivatives have been identified and developed to inhibit the Hsp90 protein folding machinery. 17-AAG, a geldanamycin analogue, is currently in clinical trials for the treatment of several types of cancer. Recent work has produced improved radicicol analogues that show promising Hsp90 inhibitory activity in vitro. In addition, chimeric molecules of these two natural products are active in vitro and represent a novel class of Hsp90 inhibitors for cancer treatment. In addition to their chemotherapeutic uses, natural product inhibitors and their derivatives have been utilized to probe the biological mechanisms by which Hsp90 inhibition regulates tumor cell growth. As a consequence of these studies, the molecular chaperones have emerged as an exciting new class of therapeutic targets. This review will highlight the utility of the natural products, geldanamycin and radicicol, as well as improved analogues and the activities exhibited by these compounds against various cancer cell lines.     

Recent progress of natural products in tumor prevention and treatment by regulating the reactive oxygen species level

Reactive oxygen species (ROS) is widespread in living organisms. Under normal conditions, ROS remains at low concentrations to maintain normal cell function. Studies have found that the abnormal elevation of ROS levels in normal tissues is an important mechanism underlying the tumorigenesis. However, high concentrations of ROS also have toxic, genotoxic, and even apoptotic effects on tumor cells. ROS has become one of the important targets for cancer prevention and treatment. Natural products widely exist in nature and have a wide range of pharmacological activities, which can affect the function of ROS. In the present study, we reviewed the research progress of natural products in tumor prevention and treatment by regulating ROS level in recent years.     

Targeted-gene silencing of BRAF to interrupt BRAF/MEK/ERK pathway synergized photothermal therapeutics for melanoma using a novel FA-GNR-siBRAF nanosystem

Melanoma is significantly associated with mutant BRAF gene, a suitable target for siRNA-based anti-melanoma therapy. However, a tumor-specific delivery system is a major hurdle for clinical applications. Here, we developed a novel nano-carrier, FA-GNR-siBRAF for safe topical application, which consists of folic acid (FA) as the tumor-targeting moiety, golden nanorods (GNR) providing photothermal capability to kill tumor cells under laser irradiation, and siRNA specifically silencing BRAF (siBRAF). The in vitro and in vivo results revealed that FA-GNR-siBRAF displayed high transfection rates, and subsequently induced remarkable gene knockdown of BRAF, resulting in suppression of melanoma growth due to the interruption of the MEK/ERK pathway. Combinatorial photothermal effects and BRAF knockdown by FA-GNR-siBRAF effectively killed tumor cells through apoptosis, with enhanced efficiency than individual treatments. Therefore, the FA-GNR-siBRAF simultaneously induced BRAF gene silencing and photothermal effects which achieved synergistic efficacy in the treatment of melanoma, paving a new path for developing clinical treatment methods for melanoma.     

抗心肌纤维化天然产物的研究进展

心肌纤维化是一种常见的临床疾患，可导致心源性猝死、心律失常和心力衰竭等疾病，研发有效的治疗药物显得尤为重要。近年来大量研究表明，天然产物在预防和治疗心肌纤维化方面有巨大潜力。本文归纳和总结了抗心肌纤维化天然产物的研究进展，为探寻抗心肌纤维化的活性先导物以及天然产物的深入研究和开发提供参考。     

New Delivery Route of Gambogic Acid Via Skin for Topical Targeted Therapy of Cutaneous Melanoma and Reduction of Systemic Toxicity

Cutaneous melanoma is the deadliest form of skin cancer, and gambogic acid (GA) exhibits potent anti-melanoma activity. However, clinical application of GA via intravenous injection and oral administration is limited by systemic toxicity and rapid metabolism in the blood. Here, we developed a new, topical route of GA delivery for anti-melanoma activity and reduction of systemic toxicity. The results indicated that the barrier of the stratum corneum (SC) and low diffusion of GA in the hydrophilic viable skin (epidermis and dermis) limited the GA penetration through intact skin. The combination of azone (AZ) and propylene glycol (PG) showed obvious synergistic effects on skin penetration by GA via improving the permeability of the SC and greatly increasing the skin accumulation of GA, thereby forming a high drug concentration in the skin and achieving a topical targeted treatment of melanoma. In addition, GA (AZ–PG) achieved the same anti-melanoma effect via topical delivery as via intravenous injection. Intravenous injection and oral administration of GA induced remarkable pathological changes in various organs in mice, whereas GA was not toxic to various organs or to the skin via topical delivery. These findings indicated that topical administration of GA is an alternative route for melanoma treatment.