Renal and haemopoietic proliferative defects as a delayed consequence of cis-platin, adriamycin and daunomycin treatments.

The long-term effects of Adriamycin (ADR), daunomycin (DMN) and cis-dichlorodiammine platinum (II) (DDP) on the ability of murine renal tubular epithelium and erythropoiesis to respond to an acute proliferative stress was investigated. Folic acid (FA) and acute anaemia induced by bleeding were used as acute proliferative stimuli for renal-tubule epithelium and erythropoiesis respectively. The ability of these normal cell-renewal systems to mount a regenerative proliferative response was evaluated by radioisotopic, morphological and gravimetric techniques 4 months after drug treatment. The results indicate that pretreatment with these agents produce a long-lasting reduction in the ability of these cell-renewal systems to mount regenerative proliferation. In the kidney, the ability to respond to FA was most severely compromised by ADR and DDP, whereas in the erythropoietic system all 3 agents induced a long-lasting proliferative defect

A high-throughput and sensitive method to measure Global DNA Methylation: Application in Lung Cancer

<p>Abstract</p> <p>Background</p> <p>Genome-wide changes in DNA methylation are an epigenetic phenomenon that can lead to the development of disease. The study of global DNA methylation utilizes technology that requires both expensive equipment and highly specialized skill sets.</p> <p>Methods</p> <p>We have designed and developed an assay, <it>CpG</it>lobal, which is easy-to-use, does not utilize PCR, radioactivity and expensive equipment. <it>CpG</it>lobal utilizes methyl-sensitive restriction enzymes, HRP Neutravidin to detect the biotinylated nucleotides incorporated in an end-fill reaction and a luminometer to measure the chemiluminescence. The assay shows high accuracy and reproducibility in measuring global DNA methylation. Furthermore, <it>CpG</it>lobal correlates significantly with High Performance Capillary Electrophoresis (HPCE), a gold standard technology. We have applied the technology to understand the role of global DNA methylation in the natural history of lung cancer. World-wide, it is the leading cause of death attributed to any cancer. The survival rate is 15% over 5 years due to the lack of any clinical symptoms until the disease has progressed to a stage where cure is limited.</p> <p>Results</p> <p>Through the use of cell lines and paired normal/tumor samples from patients with non-small cell lung cancer (NSCLC) we show that global DNA hypomethylation is highly associated with the progression of the tumor. In addition, the results provide the first indication that the normal part of the lung from a cancer patient has already experienced a loss of methylation compared to a normal individual.</p> <p>Conclusion</p> <p>By detecting these changes in global DNA methylation, <it>CpG</it>lobal may have a role as a barometer for the onset and development of lung cancer.</p

Effects of platinum/taxane based chemotherapy on acute perfusion in human pelvic tumours measured by dynamic MRI

Dynamic contrast enhanced MRI (DCE-MRI) is being used increasingly in clinical trials to demonstrate that vascular disruptive and antiangiogenic agents target tumour microcirculation. Significant reductions in DCE-MRI kinetic parameters are seen within 4–24 and 48 h of treatment with vascular disruptive and antiangiogenic agents, respectively. It is important to know whether cytotoxic agents also cause significant acute reductions in these parameters, for reliable interpretation of results. This study investigated changes in transfer constant (Ktrans) and the initial area under the gadolinium curve (IAUGC) following the first dose of chemotherapy in patients with mostly gynaecological tumours. A reproducibility analysis on 20 patients (using two scans performed on consecutive days) was used to determine the significance of DCE-MRI parameter changes 24 h after chemotherapy in 18 patients. In 11 patients who received platinum alone or with a taxane, there were no significant changes in Ktrans or IAUGC in either group or individual patient analyses. When the remaining seven patients (treated with a variety of agents including platinum and taxanes) were included (n=18), there were also no significant changes in Ktrans. Therefore, if combination therapy does show changes in DCE-MRI parameters then the effects can be attributed to antivascular therapy rather than chemotherapy

Dna-dependent-dna-polymerase. Possible limiting influence on cell reproduction during viral leukemogenesis.

Evidence is presented that during viral leukemogenesis spleen cell nuclei show an increase in labelling index and mean grain count, that is not accompanied by any changes in the nuclear level of DNA-polymerase-alpha. It is suggested that polymerase production remains under the control of the normal cell mechanisms and the virus may affect cell proliferation by altering the primer-template levels