Biomedical subjects

Tian Zhang

Publications and source records attributed to Tian Zhang.

3 recordsLinked to original sources

PubMed2026

Glucose-TOR Signaling Regulates Root Hair Elongation in Arabidopsis via the RHD6-RSL4 Transcriptional Cascade.

Root hairs are tubular protrusions of root epidermal cells that expand the root surface area to facilitate water and nutrient uptake. The target of rapamycin (TOR) kinase has been identified as a positive regulator of root hair elongation, and the RHD6-RSL4 bHLH transcriptional cascade is well established as a core module that governs root hair morphogenesis. However, whether TOR signaling acts upstream of the RHD6-RSL4 pathway and how glucose signals are integrated into this transcriptional regulatory network during root hair development remain incompletely understood. In this study, transcriptome profiling combined with pharmacological and genetic functional assays was performed to elucidate the TOR-mediated transcriptional regulatory pathway of root hair elongation in Arabidopsis. Chemical inhibition of TOR triggered genome-wide transcriptional reprogramming in seedling roots, including disruption of auxin and ethylene signal transduction and pronounced downregulation of hundreds of genes related to root hair development. Glucose-activated TOR signaling modulates the expression of root hair-specific (RHS) genes mainly through the core RHD6-RSL4 transcriptional cascade. The transcription of RSL1-RSL5 was strongly dependent on functional TOR activity, whereas RHD6 transcript abundance was specifically induced by glucose-TOR signaling under carbon-starvation recovery conditions. Genetic overexpression of either RHD6 or RSL4 partially rescued root hair elongation defects caused by TOR suppression, confirming that the RHD6-RSL4 cascade functions as a critical downstream transcriptional module of glucose-TOR signaling. Collectively, this work establishes a transcriptional framework in which glucose-TOR signals modulate root hair elongation via transcriptional activation of the master bHLH regulators RHD6 and RSL4.

RHD6-RSL4 cascade↗

PubMed2026

Phase II Randomized Trial of Radium-223 Dichloride and Cabozantinib in Patients With Renal Cell Carcinoma With Bone Metastases: RADICAL (Alliance A031801).

PURPOSE: Bone metastases (BM) occur in approximately 30% of patients with metastatic renal cell carcinoma (mRCC) and are associated with poor survival and symptomatic skeletal events (SSEs). Radium-223, an alpha-emitting bone-seeking radioisotope, and cabozantinib, a tyrosine kinase inhibitor, have demonstrated activity in BM. RADICAL (Alliance A031801; ClinicalTrials.gov identifier: NCT04071223) evaluated cabozantinib ± radium-223 in mRCC with BM. METHODS: This phase II trial enrolled patients with mRCC of any histology with ≥1 BM. Patients were randomly assigned 1:1 to cabozantinib ± radium-223, stratified by osteoclast-targeted therapy (OTT), prior therapy, opioid use, and International mRCC Database Consortium (IMDC) risk. The primary end point was SSE-free survival (SSE-FS). Secondary end points included safety, objective response rate (ORR), progression-free survival, and overall survival (OS). A target of 124 evaluable patients was planned, with a prespecified interim futility analysis at 50% of expected SSE-FS events; the trial would stop if the stratified hazard ratio (sHR) > 1.0. RESULTS: The prespecified interim futility analysis was conducted after 90 patients were enrolled and crossed the futility boundary, leading to closure at 98 patients. The final analysis included all 98 patients. Median age was 63 years, 82.7% had clear cell histology, and 79.6% were using an OTT. IMDC risk was favorable (18.4%), intermediate (67.3%), and poor (14.3%). Median follow-up was 13.1 months. Median SSE-FS for cabozantinib with radium-223 versus cabozantinib was 16.7 versus 17.6 months (sHR, 1.46 [90% CI, 0.86 to 2.51]). Median OS was 28.3 versus 19.7 months (sHR, 1.40 [95% CI, 0.70 to 2.79]). ORR was 19.4% versus 25.0% (P = .78). Grade ≥3 adverse events were similar across arms (69.6% v 75.5%). CONCLUSION: Radium-223 did not improve SSE-FS when added to cabozantinib. The combination demonstrated a manageable safety profile.

Humans↗

PubMed2024

Molecular analysis of primary and metastatic sites in patients with renal cell carcinoma.

BACKGROUNDMetastases are the hallmark of lethal cancer, though underlying mechanisms that drive metastatic spread to specific organs remain poorly understood. Renal cell carcinoma (RCC) is known to have distinct sites of metastases, with lung, bone, liver, and lymph nodes being more common than brain, gastrointestinal tract, and endocrine glands. Previous studies have shown varying clinical behavior and prognosis associated with the site of metastatic spread; however, little is known about the molecular underpinnings that contribute to the differential outcomes observed by the site of metastasis.METHODSWe analyzed primary renal tumors and tumors derived from metastatic sites to comprehensively characterize genomic and transcriptomic features of tumor cells as well as to evaluate the tumor microenvironment at both sites.RESULTSWe included a total of 657 tumor samples (340 from the primary site [kidney] and 317 from various sites of metastasis). We show distinct genomic alterations, transcriptomic signatures, and immune and stromal tumor microenvironments across metastatic sites in a large cohort of patients with RCC.CONCLUSIONWe demonstrate significant heterogeneity among primary tumors and metastatic sites and elucidate the complex interplay between tumor cells and the extrinsic tumor microenvironment that is vital for developing effective anticancer therapies.

Humans↗