Enhanced antitumour activity of doxorubicin and simvastatin combination loaded nanoemulsion treatment against a Swiss albino mouse model of Ehrlich ascites carcinoma

Doxorubicin (DOX) is the most commonly used anticancer drug; however, it has limited use because prolonged administration may result in severe cardiotoxicity. Simvastatin (SIM), generally prescribed for hypercholesterolaemia, has also shown salubrious results in the monotherapy or combinational drug therapy of different cancers in various models. Nanoparticle drug delivery systems are a novel way of improving therapeutics and also improving the absorption and specificity of drugs towards tumour cells. In this study, we exploited this technology to increase drug specificity and minimize imminent adverse effects. In this study, the antitumour activity of the combination formulas of DOX and SIM, either loaded in water (DOX‐SIM‐Solution) or nanoemulsions (NEs) (DOX‐SIM‐NE), was evaluated in a Swiss albino mouse model of Ehrlich ascites carcinoma. The anticancer effect was assessed by quantifying the change in body weight, mean survival time, and percent increase in lifespan (%ILS), determining haematological and serum biochemical parameters (liver function test, kidney function test and lipid profile parameters) as well as studying the histopathological alterations in liver tissues. We observed a clear increase in %ILS of the DOX‐SIM‐Solution group (265.30) that was double the %ILS of the DOX‐SIM‐NE group (134.70). However, DOX‐SIM‐NE had a non‐toxic effect on the haematological parameters, whereas DOX‐SIM‐Solution increased the levels of haemoglobin and lymphocytes. Furthermore, the encapsulation of SIM and DOX into NEs improved the levels of all serum biochemical parameters compared to the DOX‐SIM‐Solution. A reduction in the side effects of DOX‐SIM‐NE on the liver was also established using light microscopy, which revealed that the morphologies of the hepatocytes of the mice were less affected by administration of the DOX‐SIM‐NE treatment than with the DOX‐SIM‐Solution treatment. The study showed that incorporating SIM into the DOX‐loaded‐NE formulation remarkably improved its efficiency and simultaneously reduced its adverse effects.     

Replicating herpes simplex virus vectors for cancer gene therapy

Attenuated viral vectors based on herpes simplex virus (HSV) are capable of killing cancer cells directly while sparing normal tissue in animal models of disease. This selective ability is likely due to the evolutionary constraints on the virus to establish lifelong infection in its host without causing destruction of normal tissues. However, extensive experimental animal data show that cancer cells are able to sustain a productive viral infection, which ultimately leads to cell death and tumour regression. Moreover, preliminary results generated in two Phase I clinical studies of modified replicating HSV for the treatment of brain tumours (e.g., glioblastoma multiforme) have been encouraging and suggest that the safety data generated in animals are predictive of human safety. Although much progress has been made in developing oncolytic HSV vectors for clinical use, there is still a long way to go to determine which combinations of virus, surgery, radiation and chemotherapy will provide improved therapy for the control and eradication of a variety of human cancers.     

Immunomodulating role of bisphosphonates on human gamma delta T cells: an intriguing and promising aspect of their antitumour activity

Vγ9Vδ2 T cells have the ability to produce inflammatory cytokines involved in protective immunity against intracellular pathogens and tumours and to display strong cytolytic as well as bactericidal activities. This suggests a direct involvement of Vγ9Vδ2 T lymphocytes in immune control of cancer and infections. These observations have recently aided development of novel immunotherapeutic approaches aimed at Vγ9Vδ2 T cell activation. Nitrogen-containing bisphosphonates (N-BPs) play a crucial role in Vγ9Vδ2 T lymphocyte activation and in the acquisition of effector functions. The preliminary results of these innovative strategies are encouraging. Moreover, compelling evidence in the literature supports the hypothesis that the antitumour effect of bisphosphonates is exerted through direct as well as indirect mechanisms. An additional and not yet well explored mechanism by which N-BPs may display antineoplastic effect is related to their immunomodulatory properties. It is fascinating that N-BPs influence the immune system in various but interrelated ways, being able to enhance the innate and to promote the adaptive immune responses. For all these reasons, Vγ9Vδ2 T lymphocytes represent a particularly interesting target for immunotherapeutic protocols based on N-BP administration. All these unexpected effects of N-BPs on the immune system have opened new and intriguing possibilities of therapeutic use for these drugs.     

Therapeutic potential of thiazolidinediones as anticancer agents

There has been great interest in the development of oncolytic viruses – viruses that selectively destroy tumour cells – as cancer therapeutics. Reovirus holds great promise as an anticancer therapy, not just because it is a wild type virus that inherently displays selective tumour cytotoxicity in cancers with active Ras signalling pathways but also because it results only in relatively benign infections with few minor symptoms. As many tumours have an activated Ras pathway, the potential for utilizing reovirus as an effective anticancer agent is substantial. The several challenges that need to be overcome in the development of oncolytic viruses as anticancer agents, including issues of systemic toxicity, tumour selectivity and immune response, are addressed in this review. Clinical studies with the objective of developing Reolysin (human reovirus serotype 3 Dearing) as a human cancer therapeutic are currently underway. The first human Phase I study with intravenous Reolysin has now been completed and further studies, including Phase I and II clinical trials using Reolysin alone and in combination with radiation or chemotherapy, delivered via local or systemic intravenous administration, have commenced.     

胃癌浸润性淋巴细胞的细胞表型及杀伤活性

目的和方法：本实验用９例胃癌患者ＴＩＬ和ＩＬ２在体外共同孵育后，用流式细胞仪分析胃癌ＴＩＬ的细胞表型特征。结果：ＴＩＬ细胞表型特征是以ＣＤ３为主，ＣＤ４／ＣＤ８为０８３，ＮＫ细胞１６３±３６％。经白细胞介素２（ＩＬ２）激活２０天后，ＣＤ３减少，ＣＤ４／ＣＤ８为１８５，ＮＫ细胞数量增至４１３±１３７％，Ｐ＜００１。ＬＤＨ释放法测定激活后的ＴＩＬ对自体胃癌细胞杀伤率比培养初期高３７４倍，变比对同时培养的７９０１胃癌细胞杀伤率高１７５倍。对自体和异体胃癌细胞杀伤作用均显著高于ＬＡＫ细胞，且具有靶细胞特异性。结论：结果表明胃癌ＴＩＬ对胃癌细胞杀伤作用，可能与ＮＫ细胞数量增多，导致胃癌细胞凋亡有关     

Sunitinib malate for the treatment of solid tumours: a review of current clinical data

Receptor tyrosine kinases (RTKs) play important roles in the regulation of cellular growth, and mutated or overexpressed RTKs have been implicated in various human cancers. Sunitinib malate is an oral multitargeted tyrosine kinase inhibitor with antitumour and antiangiogenic activity that recently received approval from the FDA for the treatment of advanced renal cell carcinoma and of gastrointestinal stromal tumours after disease progression on or intolerance to imatinib mesilate therapy. Sunitinib has also demonstrated promising clinical activity in the treatment of other advanced solid tumours. The present review provides an updated summary of emerging clinical experience with this promising new anticancer agent.     

Overview: Recent Advances in Protein Kinase C Inhibitors

Glycolipids are important components of mammalian cell membranes and play an important role as signal mediators in cellular biology. Recently, the glycolipid mediated biological pathways have been drawing researchers’ attention. There has been a resurgence of interest in the signalling roles of glycolipid derivatives in the biochemical and biomedical research field. The design of glycolipid derivatives that block cell adhesion and regulate the immune response has highlighted potential therapeutic uses in the treatment of cancer, infection and other diseases originating in cell regulation disorder. This review summarises recent developments in the design of the four kinds of glycolipid related compounds (steroidal glycoside derivatives, glycosyl ceramide derivatives, glucosamine derivatives and glycero glycolipid derivatives) for therapeutic use.     

2,3—双（酰氧甲基）—1,4—二羟基蒽醌的合成及抗肿瘤活性的研究

在1, 4-二羟基蒽醌的2,3位上,引入离去基团溴和烷氧羰基,合成了10个化合物。其中化合物10能延长L7712白血病小鼠的生命。     

Inhibitory effects of Ixora javanica extract on skin chemical carcinogenesis in mice and its antitumour activity.

Topical application of 100 mg/kg body weight of Ixora javanica flower extract inhibited the growth and delayed the onset of papilloma formation in mice initiated with 7,12-dimethylbenz[a]anthracene (DMBA) and promoted using croton oil. The extract at the same dose, when administered orally inhibited the growth of subcutaneously injected 20-methylcholanthrene (MCA)-induced soft tissue fibrosarcomas significantly. Oral administration of 200 mg/kg of the extract inhibited the growth of intraperitoneally transplanted sarcoma-180 and Ehrlich ascites carcinoma tumours besides showing an increase in the life span of the treated mice. Toxicity studies showed that the blood urea nitrogen levels were elevated post treatment. The active compounds responsible for the above inhibitory effects on tumour growth were identified as ferulic acid (4-hydroxy-3-methoxy cinnamic acid) and its regionmer 3-hydroxy-4-methoxy cinnamic acid.