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.     

Synthesis and Antitumour Activity of New Derivatives of Flavone-8-acetic Acid (FAA). Part 2: Ring-Substituted Derivatives

A range of 18 derivatives of flavone-8-acetic acid (FAA) with substituents on the 2-phenyl group have been prepared and their anti-tumour activity evaluated in vitro against a panel of human and murine tumour cell lines and in vivo against MAC 15A. There was no clear-cut relationship between in vitro and in vivo activity but the activity in each situation was found to be very sensitive to the precise substitution pattern with closely related isomers giving widely different activities. Some of the compounds, notably 10b,cj , and r , were active in vivo and these require further studies in order to evaluate their potential for development.     

Synthesis and Antitumour Activity of New Derivatives of Flavone-8-acetic Acid (FAA). Part 1: 6-Methyl Derivatives

A range of 17 derivatives of flavone-8-acetic acid (FAA) with a 6-methyl substituent have been prepared and their anti-tumour activity evaluated in vitro against a panel of human and murine tumour cell lines and in vivo against MAC 15A. While many of the compounds show activity comparable to FAA in vitro, this essentially disappears in vivo, possibly due to degradation before the compounds can reach the tumour site.     

Polyphenolic compounds from propolis modulate immune responses and increase host resistance to tumour cells

Propolis contains a variety of polyphenolic compounds. We investigated the effect of a water-soluble derivatives of propolis (WSDP) and polyphenolic compounds, components of propolis, on growth of Ehrlich ascites tumour (EAT) in mice. Tumour in peritoneal cavity was produced by 2×10⁶ EAT cells. WSDP and polyphenolic compounds (caffeic acid-CA, caffeic acid phenethyl ester-CAPE and quercetin-QU) were given to mice perorally (po). It was found that the volume of ascitic fluid induced by EAT cells and total number of cells present in the peritoneal cavity was markedly reduced in EAT-bearing mice treated with test components and the survival time of treated mice was prolonged. Inhibition of EAT growth was due to their effect on the immune system of mice. When innate and acquired immune responses were evaluated, a dose-related increase of cytotoxic T-cell, NK and B cells activity was observed in test components-treated mice. Furthermore, exposure of animals to test components increased functional activity of macrophages to produce factors regulating the function of B-, T-, and NK- cells respectively. In conclusion, these findings imply that the antitumour activity of WSDP and polyphenolic compounds of propolis enhanced host resistance in the EAT tumour model, increasing the activities of macrophages, cytotoxic T cells, B cells and NK cells.     

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.     

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     

Antitumour properties based on the self‐assembly of camptothecin and carbamoylmannose conjugates

Camptothecin (CPT) and its analogues show potent antitumour activity. However, poor water solubility and severe side effects have restricted their applications in clinical practice. In this paper, a novel self‐assembly based on camptothecin and carbamoylmannose conjugates ( CPT‐Man ) was constructed. The self‐assembly increased the water solubility of camptothecin to 0.64 mg/ml and antitumour activity. Moreover, CPT‐Man could induce obvious cancer cell apoptosis. This work provides a new approach for exploring carbohydrate‐modified antitumour properties by self‐assembled CPT drugs.     

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.