Project description:Freshwater is a limited and dwindling global resource; therefore, efficient water use is required for food crops that have high water demands, such as rice, or for the production of sustainable energy biomass. We show here that expression of the Arabidopsis HARDY (HRD) gene in rice improves water use efficiency, the ratio of biomass produced to the water used, by enhancing photosynthetic assimilation and reducing transpiration. These drought tolerant low-water-consuming rice plants exhibit increased shoot biomass under well irrigated conditions and an adaptive increase in root biomass under drought stress. The HRD gene, an AP2/ERF-like transcription factor, identified by a gain-of-function Arabidopsis mutant hrd-D having roots with enhanced strength, branching, and cortical cells, exhibits drought resistance and salt tolerance, accompanied by an enhancement in the expression of abiotic stress associated genes. Although HRD overexpression in Arabidopsis produces thicker leaves with more chloroplast-bearing mesophyll cells, in rice there is an increase in leaf biomass and bundle sheath cells that probably contribute to the enhanced photosynthesis assimilation and efficiency. HRD overexpression was also studied for clues of molecular mechanisms involved using microarrays. The results exemplify application of a gene identified from the model plant Arabidopsis for the improvement of water use efficiency coincident with drought resistance in the crop plant rice. Keywords: Genetic modification transcription factor overexpression mutant
Project description:Preclinical data support the investigation of PARP inhibitors in other neoplasms exhibiting homologous recombination deficiency (HRD) as monotherapy as well as in combination with chemotherapy. However，in colorectal cancer (CRC), the role of HRD alterations is mostly unknown. This study aims to explore the the Efficacy and Safety of Fluzoparib combined with Irinotecan in the Second-line treatment of HRD alterations metastatic colorectal cancer.
Project description:Ovarian cancer is a global problem, is typically diagnosed at a late stage and has no effective screening strategy. Platinum-based chemotherapy or Poly(ADP-ribose) polymerase inhibitors (PARPis) treatment are most frequently applied for ovarian cancer patients who are inoperable and in the advanced stage. The recognition of homologous recombination deficiency (HRD) as a biomarker to predict the effect of Platinum-based or PARPis treatment. WGS and WES can detect tumor HRD status but have several disadvantages which restrict their clinical application. My choice HRD CDx and Foundation Focus CDx are approved by FDA for HRD detection, however, whether they are applicable to the Chinese population or not is unknown. In this study, we created an SNP-based Tg-NGS panel to fill in gaps in Chinese patients’ HRD screening. Our results showed that the panel is cost and time-saving compared with WGS, but equivalent with SNP microarray on CNV and HRD detection. In summary, this newly developed kit is promising in clinical application to guide ovarian cancer and even other cancer types therapy.
Project description:Profiling of genome-wide DNA methylation and copy number in TNBCs classified as HRD by the multiplex ligation-dependent probe amplification assay
Project description:Interventions: Oxialiplatin-based therapies (FOLFOX, CapeOX), Irinotecan-based therapies (FOLFIRI, IFL, IRIS), Molecular targeting therapies (Bevacizumab, Cetuximab)
Mutational analyses of various genes
Primary outcome(s): Association between the response rate of anti-cancer drug therapies and genetic alterations
Study Design: Parallel Non-randomized
