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Biomedical subjects

Gaurav Gupta

Publications and source records attributed to Gaurav Gupta.

2 recordsLinked to original sources

Impact of older donor age in kidney transplants in a biopsy-based observational study.

Because older donor age is a major concern when considering kidneys for potential transplantation, we explored the actual effect of donor age on the features of kidneys that have been transplanted. We studied the correlations of donor age with molecular injury and rejection scores in 4,502 kidney transplant biopsies assessed by microarrays as well as function and postbiopsy survival. We used multivariable analyses to correct for the correlations of donor age with other predictive variables: recipient age, time of biopsy after transplant, and deceased versus living donors. Older donor age correlated with lower glomerular filtration rate (GFR) and increased acute and chronic injury transcripts but had no effect on rejection, which was anticorrelated with recipient age. Acute injury transcripts peaked immediately after transplant and regressed. Older donor age had little effect on acute molecular injury immediately after transplant but strongly increased molecular injury scores at later times, peaking about 1-year after transplant, indicating that older age does not increase molecular injury but increases failed repair after injury. As expected, older donor age correlated with increased chronic injury and lower GFR, evident from the earliest time after transplant, pretransplant aging. However, despite substantial age-related effects, the quantitative contribution of donor aging to molecular injury, function, and survival was very small.

Humans

Ovarian tumor cells gain competitive advantage by actively reducing the cellular fitness of microenvironment cells.

Cell competition and fitness comparison between cancer and tumor microenvironment (TME) cells determine oncogenic fate. Our previous study established a role for human Flower isoforms as fitness fingerprints, where the expression of Flower Win isoforms in tumor cells leads to growth advantage over TME cells expressing Lose isoforms. Here we demonstrate that the expression of Flower Lose and reduced microenvironment fitness is not a pre-existing condition but, rather, a cancer-induced phenomenon. Cancer cells actively reduce TME fitness by the exosome-mediated release of a cancer-specific long non-coding RNA, Tu-Stroma, which controls the splicing of the Flower gene in the TME cells and expression of Flower Lose isoform, which leads to reduced fitness status. This mechanism controls cancer growth, metastasis and host survival in ovarian cancer. Targeting Flower protein with humanized monoclonal antibody (mAb) in mice significantly reduces cancer growth and metastasis and improves survival. Pre-treatment with Flower mAb protects intraperitoneal organs from developing lesions despite the presence of aggressive tumor cells.

Female