The assessment of response of murine transplantable colon tumors to combination chemotherapy

Summary The mouse adenocarcinoma of the colon (MAC) system, which has been shown to be a good model for human colorectal carcinoma in terms of its chemosensitivity, was tested with two modified human protocols (MeCCNU+5 FU, BCNU+5 FU) in an attempt to evaluate its suitability as a model for developing new regimens of combination chemotherapy for treating patients with colorectal carcinoma. This attempted evaluation raised problems regarding, firstly, the length of time available before tumours became too large in control and non-responding hosts to maintain adequate mobility and, secondly, the assessment of response to the drugs. The commencement of drug administration 3 days after transplantation and the assessment of response by measuring delay in time for tumor growth to reach a given volume, with the results analysed by Gehan's (generalised Wilcoxon) test, gave a workable method of evaluation. This method is presented as being suitable for use in the study of transplantable solid tumor lines as models for combination chemotherapy.     

The logistics of broader pre-clinical evaluation of potential anti-cancer agents with reference to anti-tumour activity and toxicity of mitozolomide.

Anti-tumour responses with CCRG81010, M & B 39565, NSC 353451, 8-carbamoyl-3-(2-chloroethyl)imidazo [5,1-d]-1,2,3,5-tetrazin-4(3H)-one (Mitozolomide) in a panel of 4 murine colon tumours of varying growth characteristics and chemosensitivity and a spontaneous murine lymphoma are similar to those seen with standard nitrosoureas. The moderately well differentiated colon adenocarcinoma MAC 16 is nonresponsive to mitozolomide and methylCCNU. Responses in the other 4 lines studied are only achieved near to maximum tolerated dose and at this level there is severe host toxicity. Haemopoietic toxicity is clearly demonstrated by analysis of peripheral blood counts and by CFU-S assays and severe testicular and ovarian toxicity was also seen at dose levels necessary to achieve anti-tumour effects. Using mitozolomide as an example, the study has demonstrated the feasibility of conducting simple but thorough toxicity evaluation for the determination of the therapeutic index. This approach would provide invaluable guidelines for the selection for clinical trial of the most appropriate members of a series of new cytotoxic compounds.     

The interaction of aminoalkylaminoanthraquinones with deoxyribonucleic acid.

A series of aminoalkylaminoanthraquinones have been prepared as potential intercalating agents. The binding to DNA of these compounds and the known intercalating drugs chloroquine, lucanthone, daunorubicin and doxorubicin has been characterized by spectrophotometric titration. The association constant for the interaction with DNA has been determined for each compound from a Scatchard plot. The compounds synthesized had association constants between 0-5 and 4-2 times 10(6) compared with 0-93, 0-90, 3-10 and 2-49 times 10(6) for chloroquine, lucanthone, daunorubicin and doxorubicin respectively.     

Inflammatory bowel disease: A survey of the epidemiology in Asia

Inflammatory bowel disease (IBD) has long been considered a disease that affects predominantly a Western population. The incidence and prevalence rates from Asian populations are much lower in comparison. More recent data, however, have shown significantly higher rates in Asians and time trend studies have shown an increase in the incidence of ulcerative colitis (UC) and a similar but lower rise in Crohn's disease (CD). The epidemiological changes that are taking place mirror that of the Western experience seen 50 years previously and seem to occur in parallel with the rapid socioeconomic development taking place in Asia. It appears that certain racial groups are more prone than others to develop IBD. For instance, Indians in South‐East Asia have higher rates compared to Chinese and Malays. While there is host genetic predisposition, environmental factor(s) may be responsible for this difference. Migrant studies of South Asians in the UK, where second‐generation immigrants have assumed incidence rates as high as the indigenous whites and Asian Jews who develop high incidence rates comparable to Jews from Europe or North America in Israel point to the role of environmental factors. It is unclear which specific factors are responsible. Studies have suggested a change in diet to a more Westernized one may underlie this epidemiological change in the Asian population. It is likely that there are racial groups amongst Asians who are more susceptible to IBD and who will demonstrate a higher frequency of IBD when exposed to putative environmental factors.     

Heart rate reduces when stroke patients are touched . . . And??

McFadden KL, Hernández TD. Cardiovascular benefits of acupressure (Jin Shin) following stroke. Complement Ther Med 2010; 18: 42–8.