Indian scientists find genetic clues to tackle oral cancer among women

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New Delhi, (IANS) A team of Indian scientists has discovered oral cancer-causing driver gene mutations in women patients in southern parts of the country.

The team from the Jawaharlal Nehru Centre for Advanced Scientific Research (JNCASR), Bengaluru and the BRIC-National Institute of Biomedical Genomics (NIBMG), Kalyani, in collaboration with clinicians from Sri Devraj Urs Academy of Higher Education and Research (SDUAHER), Kolar, conducted a female-centric study on oral cancer in India with a unique tobacco chewing habit.

This study led by Professor Tapas K Kundu, JNCASR, Bengaluru aimed to understand what makes cancers in women unique, how the disease manifests and progresses in female patients and how we can treat them better.

The team also used artificial intelligence (deep learning) to digitally analyse tumour tissues. This revealed two distinct groups of female patients, each with a different immune response in their tumours.

India carries one of the world’s heaviest burdens of oral cancer with alarmingly high rates witnessed among women in certain regions, especially in southern and northeast India, due to the widespread habit of chewing tobacco-infused betel quid, gutka, and related products.

While the disease is widely studied in men, oral cancer in women has often remained under the radar.

The study was performed on paired tumour and blood samples from female OSCC-GB patients with a unique regional tobacco-chewing habit (Kaddipudi), commonly observed among women in the Kolar district of Karnataka.

Analysis of this women-centric cohort has revealed a unique driver mutation implicated in oral tumorigenesis.

This investigation, published in the Clinical and Translational Medicine Journal, was specifically designed to uncover the biological underpinnings of the disproportionately aggressive, highly recurrent, and life-threatening forms of oral cancer that affect Indian women.

Using cutting-edge whole-exome sequencing, the researchers identified ten key genes with significant mutations in the female oral cancer cohort from Kolar, Karnataka.

Although two of the major genes, CASP8 and TP53, were found to be highly mutated in these patients, uniquely, CASP8 seems to be the driver mutation (cancer-causing), which is quite different compared to previously studied mutations in oral cancer patients (largely men).

The findings suggest that co-occurring TP53 and CASP8 mutations confer a markedly aggressive and lethal phenotype in oral cancer.The team is now focused on delineating the molecular mechanisms of oncogenesis driven by this novel driver mutation within the background of TP53 alterations for the next phase of the research. Indian scientists find genetic clues to tackle oral cancer among women | MorungExpress | morungexpress.com
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Australia leads first human trial of one-time gene editing therapy to halve bad cholesterol


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Melbourne, November 10 (IANS): Researchers in Australia have led a first-in-human trial for a breakthrough gene-editing therapy that halves bad cholesterol and triglycerides in people with difficult-to-treat lipid disorders.

The trial tested CTX310, a one-time CRISPR-Cas9 gene-editing therapy that uses fat-based particles to carry CRISPR editing tools into the liver, switching off the ANGPTL3 gene. Turning off this gene lowers LDL (bad) cholesterol and triglycerides, two blood fats linked to heart disease, according to a statement released Monday by Australia's Monash University.

The Victorian Heart Hospital, operated by Monash Health in partnership with Monash University, treated three of 15 patients aged 18-75 years with difficult-to-treat lipid disorders in phase 1 of the global trial conducted across Australia, New Zealand, and Britain, the statement said, Xinhua news agency reported.

At the highest dose, a single-course treatment with CTX310 resulted in a mean reduction of LDL cholesterol by 50 per cent and triglycerides by 55 per cent, remaining low for at least 60 days after two weeks of treatment, it said, adding LDL cholesterol and triglycerides were reduced by nearly 60 per cent among all participants with various doses, with only mild, short-term side effects reported.

Importantly, CTX310 is the first therapy to achieve large reductions in both LDL cholesterol and triglycerides at the same time, marking a potential breakthrough for people with mixed lipid disorders who have elevations in both, according to the trial published in the New England Journal of Medicine.

"The possibility of a single-course treatment with lasting effects could be a major step in how we prevent heart disease," said Stephen Nicholls, Director of the Victorian Heart Hospital, and study lead investigator."It makes treatment easier, reduces ongoing costs, relieves pressure on the health system, all while improving a person's quality of life," Nicholls said, emphasising plans to focus on larger and more diverse patient populations in future trials of CTX310. Australia leads first human trial of one-time gene editing therapy to halve bad cholesterol | MorungExpress | morungexpress.com
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