槐定碱的抗肿瘤药理作用研究进展

体外实验发现槐定碱能浓度相关地抑制大肠癌LS174t细胞、SW620细胞、SW480细胞、HCT-116细胞,胃癌BGC823细胞、MGC-803细胞、SGC7901细胞、MKN45细胞、MKN28细胞,胰腺癌capan-1细胞,肝癌97H细胞、Bel细胞、HepG2细胞,食管癌EC109细胞,食管胃交界腺癌OE-19细胞、SK-GT2细胞,白血病K562细胞、HL60细胞,淋巴瘤U937细胞,骨髓瘤NS-1细胞,乳腺癌MCF-7细胞,卵巢癌PM-2细胞、SKVO3细胞,宫颈癌HeLa细胞,肺癌A549细胞、NCI细胞,DMS153细胞,黑素瘤A375细胞,舌鳞癌TCA8113细胞,神经胶质瘤U87细胞、U87MG细胞,前列腺癌PC3细胞增殖。整体实验发现槐定碱抑制SW480细胞、HCT-116细胞,白血病L1210细胞,肺癌Lewis细胞,肉瘤S180细胞、S37细胞、W256细胞、EAC细胞移植瘤在小鼠或大鼠体内生长。临床上槐定碱已被试用于治疗恶性滋养细胞肿瘤、消化道肿瘤、恶性淋巴瘤,有开发成抗肿瘤新药的潜力。     

苦参碱和氧化苦参碱抗大肠癌药理作用研究进展

苦参碱和氧化苦参碱能防治氧化偶氮甲烷/葡聚糖硫酸钠诱发小鼠原发性结直肠癌和CT26细胞或SW480-EGFP细胞移植瘤在大鼠或小鼠体内生长。体外实验发现苦参碱和氧化苦参碱能浓度相关地抑制大肠癌SW480细胞、SW480-EGFP细胞、SW480/M5细胞、SW620细胞、SW1116细胞、LoVo细胞、HT-29细胞、Colon26细胞、HCT116细胞、HCT-8细胞、HCL细胞和LS174t细胞增殖,并诱导凋亡。苦参碱能增强奥沙利铂抗SW480细胞、SW620细胞和SW1116细胞的作用。氧化苦参碱能增强5-氟尿嘧啶抗LoVo细胞的作用。     

苦参碱对上消化系肿瘤临床药理作用的研究进展

苦参碱能防治大鼠胃癌前病变以及乙基硝基亚硝基胍诱发大鼠原发性胃癌,也能防治人胃癌MKN-45细胞、SGC-7901细胞、BG823细胞、人胰腺癌BxPC-3细胞移植瘤在裸鼠或大鼠体内生长。经体外实验发现,苦参碱能浓度相关地抑制人胃癌SGC-7901细胞、MGC803细胞、BGC823细胞、MKN-45细胞、NCI-N87细胞、AGS细胞、人胰腺癌BxPC-3细胞、CFPAC-1细胞、人胆管癌QBC939细胞、人胆囊癌GSC-SD细胞、人食管癌Eca109细胞、Escl细胞的增殖并诱导其凋亡。经体内外实验结果发现,苦参碱能增强化疗药抗人胃癌SGC-7901细胞作用。综述苦参碱对消化系肿瘤临床药理作用的研究文献,并对其研究进展做了分析。     

苦参碱抗乳腺癌和卵巢癌的药理作用研究进展

苦参碱能呈剂量相关地抑制乳腺癌MCF-7细胞、Bcap-37细胞、MA737细胞、Walker256细胞、TM40D细胞、4T1细胞、SK-BR-3细胞、MDA-MB-231细胞,以及卵巢癌NuTu19细胞、SKOV3细胞、A21-2细胞、OV2008细胞、HO-8910PM细胞、PA-1细胞、PM-2细胞、3AO细胞、OVCAR3细胞生长并诱导凋亡。苦参碱是这些癌细胞的自噬早期诱导剂,更是自噬晚期抑制剂,通过诱导线粒体凋亡和内质网应激的2个途径引起癌细胞凋亡的,因而能提高癌细胞对放、化疗的敏感性。苦参碱增强机体的免疫调节功能也是其抗癌作用机制的一部分,并能对抗放化疗抑制免疫的毒副作用发生。     

苦参碱抗肝癌药理作用及临床应用的研究进展

苦参碱能防治二乙基亚硝胺诱发大鼠原发性肝癌和小鼠肝癌H22细胞移植瘤在小鼠体内的生长。体外实验发现苦参碱能浓度相关地抑制肝癌H22细胞、SMMC-7721细胞、BEL-7402细胞、BEL-7404细胞、Hep3B细胞、QGY细胞、QGY/CDDP细胞、97H细胞、CRBH-7919细胞、CRBH-7919/mdr1细胞增殖、黏附、迁移、侵袭并诱导凋亡,也能诱导人肝癌SMMC-7721细胞、BEL-7402细胞、BEL-7404细胞、化学品诱发肝癌大鼠体内的低分化肝卵圆细胞分化,也能提高荷瘤机体的免疫调节功能。临床上苦参碱注射液正在试用于肝癌的治疗和复发的预防。     

Ts-SV40 介导的温敏细胞研究现状

非永生化细胞在体外的传代次数、 增殖活性是有限的, 在应用于细胞治疗或者是体外研究中会受到细胞数量的限制。转染有 ts-SV40LT 基因的细胞在许可温度下具有最大的增殖活性, 在许可温度进行细胞扩增能弥补细胞数量不足的限制, 非许可温度可用于细胞治疗或研究其生理特性。其研究领域涉及腹膜的间质细胞、 泌尿道肌卫星细胞、 口腔上皮细胞、 肾上腺髓质细胞、 骨髓血管内皮细胞、 视网膜祖细胞、 间充质干细胞、 造血干细胞、 肥大细胞、 足细胞、 库普弗细胞等。本文对 ts-SV40 介导的温敏细胞的研究现状做一综述。     

和厚朴酚及厚朴酚抗结直肠癌和胃癌药理作用及其机制的研究进展

和厚朴酚及厚朴酚是疏水性联苯酚类结构的同分异构体。和厚朴酚能防治结直肠癌CT26细胞或RKO细胞移植瘤在小鼠体内生长,并延长荷瘤小鼠的生存时间。体外实验发现和厚朴酚及厚朴酚能浓度相关地抑制结直肠癌SW480细胞、SW620细胞、LoVo细胞、LS180细胞、CT26细胞、RKO细胞、Caco-2细胞、COLO-205细胞、HCT-8细胞、HCT15细胞、HCT116细胞增殖,并诱导细胞凋亡。在HCT116细胞中,hMLH1错配修复缺失型细胞对和厚朴酚的敏感性高于完整型细胞。和厚朴酚是通过调控JNK/Nur77/AMPK、TGF-β1/p38MAPK/Hippo、BMP7/TGF-β1/p53和BMP7/PTEN/AKT 4条信号转导通路诱导结直肠癌细胞凋亡,还通过抑制血管内皮生长因子的表达,阻滞肿瘤内新生血管形成,抑制结直肠癌生长。和厚朴酚及厚朴酚还能抑制胃癌MGC-803细胞和SGC-7901细胞的增殖。     

氧化苦参碱抗肝癌作用及机制的药理作用研究进展

氧化苦参碱能防治二乙基亚硝胺或2-乙酰氨基芴诱发大鼠原发性肝癌和小鼠肝癌H22细胞移植瘤在小鼠体内的生长。体外研究发现氧化苦参碱能浓度相关地抑制肝癌HepG2细胞、SMMC-7721细胞、BEL-7402细胞、BEL-7404细胞、QGY细胞、QGY-7703细胞、97H细胞的增殖并诱导其凋亡,还可能诱导HepG2细胞、BEL-7402细胞、PLC/PRF/5细胞的分化,也能提高荷瘤机体的免疫调节功能。综述氧化苦参碱抗肝癌作用及机制的药理作用文献,并对其研究进展做了分析。     

葫芦素B纳米脂质载体对结肠癌和乳腺癌细胞抑制及凋亡作用的研究

目的：研究葫芦素B纳米脂质载体（CuB-NLC）对结肠癌Lovo细胞,乳腺癌MCF-7细胞的体外细胞毒性。方法：结肠癌Lovo细胞,乳腺癌MCF-7细胞常规复苏、培养及传代,取处于对数生长期的细胞用于实验。采用CCK-8法检测质量浓度为0、0.0625、0.25、1.00、4.00、16.0 mg/L的CuB-NLC对结肠癌Lovo细胞,乳腺癌MCF-7细胞的毒性,流式细胞仪检测结肠癌Lovo细胞,乳腺癌MCF-7细胞的细胞周期进程及Annexin V/PI双染法检测细胞的凋亡率。结果：与葫芦素B （CuB）相比CuB-NLC对结肠癌Lovo细胞,乳腺癌MCF-7细胞生长抑制作用明显增强（P＜0.05）,且这种抑制作用随药物浓度增加而增强。CuB组及CuB-NLC组作用于结肠癌Lovo细胞、乳腺癌MCF-7细胞48 h后,与NLC空白组及DMSO对照组相比较,CuB及CuB-NLC均能够引起结肠癌Lovo细胞、乳腺癌MCF-7细胞G2/M期阻滞,同时伴有G0/G1期细胞减少, CuB-NLC组的作用更加明显,有统计学差异（P＜0.05）。Annexin V/PI双染法检测结果表明,CuB-NLC能显著诱导结肠癌Lovo细胞,乳腺癌MCF-7细胞凋亡。结论：葫芦素B纳米脂质载体能够抑制结肠癌Lovo细胞,乳腺癌MCF-7细胞的增殖,诱导细胞凋亡。     

急性髓性白血病患者外周血淋巴细胞亚群的检测及其临床意义

目的探讨急性髓系白血病(AML)患者外周血T淋巴细胞亚群、DNT细胞、NK细胞的表达水平及其临床意义。方法采用流式细胞术对40例初发AML患者、32例AML完全缓解(CR)患者及20例正常人外周血T淋巴细胞亚群、DNT细胞及NK细胞水平进行检测。结果初发AML组与正常对照组比较,CD4+细胞、CD4+/CD8+比值、DNT细胞及NK细胞明显降低(P<0.05);CD3+细胞、CD8+细胞变化不显著(P>0.05)。复治CR组与对照组比较,NK细胞明显降低(P<0.05),其他各值差异无统计学意义。结论初发AML患者的T淋巴细胞亚群、DNT细胞、NK细胞变化明显,而治疗缓解后淋巴亚群基本恢复正常,说明T淋巴细胞亚群、DNT细胞、NK细胞水平检测在评价AML疗效及判断预后方面具有一定的临床价值。     

Cell death in the IPLB-LdFB insect cell line: facts and implications

The present review summarizes findings on stress-induced cell death in the IPLB-LdFB insect cell line derived from the larval fat body of the lepidopteron Lymantria dispar. Apoptotic, oncotic and autophagic cell death have been described in these cells as a consequence of oxidative stress or ATP deprivation, and similarities between IPLB-LdFB and mammalian apoptotic pathways have been highlighted. Furthermore, starting from observations in the IPLB-LdFB cells, a link has been surmised between relevance of autophagic cell death and developmental processes in the metazoan taxa.     

Carbon nanotube exploration in cancer cell lines

Complete with extraordinary structures and properties, carbon nanotubes (CNTs) have recently emerged as a potential new option for use in cancer treatment. During recent years, cancer cell lines have also been explored as prominent experimental models for evaluating pharmacokinetic parameters, cell viability, cytotoxicity and drug efficacy in tumor cells. Thus, cell lines have emerged as the best-fit model that has been thoroughly investigated and explored. This review focuses on potential applications and a compilation of various cancer cell lines used to evaluate CNT efficacy on one platform. This is likely to aid the researchers in exploring another dimension of CNTs in cancer treatment.     

Synthesis and cytotoxicity on sensitive and doxorubicin-resistant cell lines of new pyrrolo[2,1-c][1,4]benzodiazepines related to anthramycin

A new 7,8-methylenedioxy analogue (4) of (+)-porothramycin B (2) and its water-soluble sodium bisulfite derivative (15) have been synthesized in high yields and have been shown to exhibit high cytotoxic activities against several tumor cell lines. The new pyrrolo[2,1-c][1,4]benzodiazepine 4 was as effective against the resistant cell lines as against the doxorubicin-sensitive cell lines tested.     

The production of secondary metabolites by plant cells cultivated in bioreactors1

Plant cell cultures are a potential source of pharmaceutically important plant metabolites. In the past few years a lot of success has been achieved in the field of the cultivation of plant cells on a large scale. Special bioreactor systems, such as airlift or drum-type fermentors have been devised for the mass cultivation of plant cells. Classical stirred-tank bioreactors (up to 75000 l volume) have also been used for the cultivation of plant cells and the production of important plant metabolites. Plant cells proliferate much slower than microbial cells. In consequence, the time taken to grow a plant cell suspension from the shake-flask level (300 ml) to the production scale (20,000 l) takes about 3 to 6 weeks. Nevertheless, the cost analyses available show that the production of valuable chemicals by a suitable plant cell culture process could be commercially viable. Plant cells have been grown in batch and repeated batch culture, and single- stage as well as two-stage processes have been developed for the production of secondary metabolites by fermentor-cultured plant cells. There are, however, only few cell culture processes that have attracted industrial attention as yet. Biological rather than technological problems are the main obstacles to a more common use of fermentor-cultured plant cells in industry.     

Chemical profiles and monitoring dynamics at an individual nerve cell in Planorbis corneus with electrochemical detection

The identified dopamine cell of Planorbis corneus is described as a model system to study neurotransmitter storage and dynamics. Techniques developed with this model system include capillary electrophoresis with electrochemical detection and microelectrochemistry at single cells. These techniques provide a powerful combination to examine single cell neurochemistry. Whole cell and cytoplasmic dopamine concentrations have been quantified with capillary electrophoresis. Additionally, this technique has been used to profile amino acids and to quantify two compartments of neurotransmitter in a single cell. Individual exocytosis events have been monitored at the cell body of the dopamine cell of P. corneus with microelectrodes. In this case, two different types of vesicles have been identified based on the amount of transmitter released. The psychostimulant, amphetamine, has been shown to selectively affect the amount of dopamine in these vesicles with lower to higher doses affecting the larger to smaller vesicle types, respectively. Microelectrochemistry at single nerve cells has also been used to demonstrate reverse transport of dopamine across the cell membrane and to suggest a role of this process in the molecular mechanism of amphetamine.     

Epinephrine synthesis in the PC12 pheochromocytoma cell line

PC12 is a rat pheochromocytoma cell line which has been increasingly used as a model system for both neural differentiation and chromaffin cell function. PC12 cells have been reported to synthesize dopamine and norepinephrine, but not epinephrine. We have found that PC12 cells do synthesize small amounts of epinephrine and that dexamethasone increases both epinephrine content as well as phenylethanolamine-N-methyltransferase (PNMT) activity. These results suggest that the PC12 cell line may be useful in the investigation of the regulation of PNMT.     

Mechanisms of antihistamines and mast cell stabilizers in ocular allergic inflammation

Mast cells play a central role in allergic reactions and inflammation. Successful anti-allergic therapies have typically targeted mast cell mediators, particularly histamine. Antihistaminic compounds interact with the various histamine receptors found on many cells, whereas other compounds such as disodium cromoglycate, are referred to as mast cell stabilizers, as they inhibit degranulation. Some of the most successful compounds developed recently are dual-action, in that they have both anti-histaminic and mast cell stabilizing activities. Recent trends in pharmaceutical intervention, however, have been focused on the secondary effects of mast cell mediators on epithelial cell adhesion molecule expression and mediator release in the process of allergic inflammation. Since, the ocular mucosa is highly exposed to environmental allergens it is commonly involved in allergic reactions and, as such, has been a useful and accessible model in which to test new therapies in vivo. These ocular allergen provocation studies permit analysis of ocular surface cells and evaluation of tear film mediators. Furthermore, techniques to purify conjunctival mast cells have facilitated the study of the effects of mast cell stabilizing compounds on other mast cell mediators, such as cytokines, and the direct effects of mast cell mediators on epithelial cells in vitro. This review will discuss current understanding of how anti-histamines and mast cell stabilizers work, particularly in the context of molecular mechanisms of ocular allergic inflammation.     

Regenerative Therapies for Central Nervous System Diseases: a Biomaterials Approach

The central nervous system (CNS) has a limited capacity to spontaneously regenerate following traumatic injury or disease, requiring innovative strategies to promote tissue and functional repair. Tissue regeneration strategies, such as cell and/or drug delivery, have demonstrated promising results in experimental animal models, but have been difficult to translate clinically. The efficacy of cell therapy, which involves stem cell transplantation into the CNS to replace damaged tissue, has been limited due to low cell survival and integration upon transplantation, while delivery of therapeutic molecules to the CNS using conventional methods, such as oral and intravenous administration, have been limited by diffusion across the blood–brain/spinal cord-barrier. The use of biomaterials to promote graft survival and integration as well as localized and sustained delivery of biologics to CNS injury sites is actively being pursued. This review will highlight recent advances using biomaterials as cell- and drug-delivery vehicles for CNS repair.     

Integrins as attractive targets for cancer therapeutics

Integrins are transmembrane receptors that have been implicated in the biology of various human physiological and pathological processes. These molecules facilitate cell–extracellular matrix and cell–cell interactions, and they have been implicated in fibrosis, inflammation, thrombosis, and tumor metastasis. The role of integrins in tumor progression makes them promising targets for cancer treatment, and certain integrin antagonists, such as antibodies and synthetic peptides, have been effectively utilized in the clinic for cancer therapy. Here, we discuss the evidence and knowledge on the contribution of integrins to cancer biology. Furthermore, we summarize the clinical attempts targeting this family in anti-cancer therapy development.     

Biophysical methods for monitoring cell-substrate interactions in drug discovery

Cell-substrate interactions are implicated in a number of relevant pathways for drug targets such as angiogenesis, arteriosclerosis, chronic inflammatory diseases, and carcinogenesis. Moreover, cell adhesion and cytoskeletal activity have served as valuable indicators for cytotoxicity, cell density, and cell morphology. This review focuses on impedance, capacitance, resonant frequency, and refractive index measurements for monitoring cell adhesion in real time and without the use of cell labeling. ECIS, QCM, and OWLS deliver information about the cell-substrate interactions, cell-cell contact, and the strength of cell adhesion. Because of high sensitivity of these assays, events down to the single cell level have been observed, and resolutions at the nanometer level of cell-substrate distances have been achieved. The physical principles, including assay sensitivity and selectivity, are discussed in the context of cellular pathways of cell adhesion and migration. With the miniaturization of these types of sensors, cell migration and adhesion measurements in combination with specific fluorescent assays might thus deliver a high-content platform for drug development.