Researchers working on certain cancer translational medicine projects often depend on animal models that do not reflect the human disease pathology. This might be part of the reason for failure of many cancer therapies, experts at an international symposium felt.
Speaking on cancer therapy at the meet 'Trends in Translational Medicine: Bedside to Bench to Bedside', Vishva Dixit of California-based Genetech Inc. said there were fundamental differences between spontaneous and transplanted tumors that cancer researchers need to understand.
"The fraction of cells dividing in a tumor is lesser than in the surrounding normal tissue. So there is a need to model tumors in a way that the numbers of cells in mitosis are less than in the normal tissue," he said at the meet held at the National Centre of Biological Sciences in Bangalore on December 6 and 7.
Outlining the negatives of using nude mouse models, Dixit said almost every cell that is put into such models is committed to divide. "So, these tumors are very sensitive to cell cycle inhibitors. Also, the mice are immuno-compromised and this is not true for a patient with a cancer," he observed. Moreover, most of these tumors in nude mice are benign and hence the mice do not die of the disease.
However, nude mice models are good for cancers like Burkitts Lymphoma where almost all cells are committed to divide but not for most other cancers, he said.
Edward Holmes of the Bio Medical Research Council in Singapore said the goals of translational medicine were to advance the understanding of human disease and to use this to improve health. "Translational Research begins with trying to study the patient and the disease, goes to basic research and comes back to the patients for clinical trials. A clinician scientist needs dual training and almost 80 per cent protected time to do research," he pointed out.
Citing 'Biopolis' in Singapore as a perfect example of creating a conducive environment for translational medicine research he said it has more than 2000 scientists and 20 private companies in a cluster with special funds and awards to encourage training individuals in both medicine and research.
India also needs to build upon its translational research, secretary to India's Department of Biotechnology (DBT) Maharaj Kishan Bhan said. "Our basic science is not strong enough and we do need to build on it but we should move in to translational research too," he said.
Reporting his team's work, Chittaranjan Yajnik from the KEM Hospital in Pune said malnutrition during gestation could be linked to obesity in adulthood. "This can be linked in particular to vitamin B12 deficiency in pregnant women," he said. Yajnik emphasised that there was a need to change the criteria for obesity in the Indian population since Indians are not obese in the classical sense but are 'centrally obese'. "Indians are diagnosed with Diabetes Type II at an age 10 years younger than their western counterparts. And many are insulin resistant," he observed.
V. Rajashekar from the Christian Medical College, Vellore quoted a study which establishes that 34 per cent of their patients with Active Epilepsy (AE) have neurocysticercosis, the most common parasitic disease of the central nervous system. If extrapolated, it is possible that 1 in a 1000 cases of AE were due to cysticercosis in the brain, he said. The cysts cause no problem when alive in the brain. The immune system responds only when the cyst is dying. His team is trying to improve on immuno-assays using serum to detect the presence of cyst in the brain to provide a cheaper alternative to Magnetic Resonance Imaging (MRI).
The problem with pig valves used in human hearts also came up for discussion when cardiosurgeon K. R. Balakrishnan from Shri Ramachandra Medical College and Research Institute, Chennai reported his work done in collaboration with mechanical engineers at IIT, Madras. "These valves are not flexible enough. Fixing with glutaraldehyde stiffens them and they do not respond as well as the normal valves," Balakrishnan said. Imaging shows that pig valves open for 25per cent lesser time than normal valves. "We need to design valves which do not have a fixed root like a pig valve fixed to a stent. A compliant root is essential," he added.
Speaking on nerve growth factor (NGF) therapy for Alzheimer's and Parkinson's disease, Mark Tuszynski from the University of California, San Diego said the therapy had shown an effect both in rats and monkeys during phase one trials. However, phase two trials had failed since the Adeno-associated virus (AAV) vector used to deliver the growth factor distributed it to less than 10 per cent of the target. Work was on to improve the vector, he said.
Among other eminent speakers were Sanjiv Sam Gambhir from the Stanford University, California; Inder Verma from The Salk Institute, San Diego, California and Atul Butte from Stanford University, California.
