Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Preoperative downstaging of renal cell carcinoma with a tumor thrombus (RCC-TT) makes thrombectomy feasible. However, treatment resistance is common and may partly be attributed to the tumor-promoting role of the tumor microenvironment (TME). Herein, we sequenced, integrated, and comprehensively analyzed multi-center, multi-omics data from 164 RCC-TT patients and identified two clinically relevant RCC-TT subtypes. We find that the poor-prognosis subtype (TT1) exhibits enhanced extracellular-matrix (ECM) remodeling driven by epithelial LOX expression. Spatial transcriptomics (ST) shows the co-localization of GPNMB macrophages, THBS2 fibroblasts, and LOX malignant cells around tumor nests in TT1 tumors, reinforcing tumor immune barriers (TIBs). Our extensive validations using cell lines, syngeneic mouse models, multiplex immunofluorescence staining, and large-scale RCC cohorts underscore the potential of LOX inhibition in disrupting TIBs, sensitizing RCC to immunotherapy, and overcoming treatment-induced phenotypic plasticity. This study provides insights into the biological underpinnings and prognosis assessment of RCC-TT, demonstrating targetable ECM-remodeling vulnerabilities.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.devcel.2025.07.010 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Quantifying evidence for phenotypic specificity (PP4) for syndromic phenotypes: Large-scale integration of rare germline FH variants from diagnostic laboratory testing for HLRCC (Hereditary Leiomyomatosis and Renal Cell Cancer) and renal cancer.
Genet Med
September 2025
Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK; The Royal Marsden NHS Foundation Trust, Fulham Road, London, UK. Electronic address:
Purpose: Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC) is a rare cancer susceptibility syndrome exclusively attributable to pathogenic variants in FH (HGNC:3700). This paper quantitatively weights the phenotypic context (PP4/PS4) of such very rare variants in FH.
Methods: We collated clinical diagnostic testing data on germline FH variants from 387 individuals with HLRCC and 1,780 individuals with renal cancer, and compared the frequency of 'very rare' variants in each phenotypic cohort against 562,295 population controls.
Bioinformatics analysis of a geneframeshift mutation in a patient with Dent disease.
Zhong Nan Da Xue Xue Bao Yi Xue Ban
May 2025
Department of Nephropathy and Rheumatology, Third Xiangya Hospital, Central South University, Changsha 410013.
Dent disease is a rare X-linked recessive inherited renal tubular disorder characterized by low molecular weight proteinuria (LMWP), hypercalciuria, nephrocalcinosis, and other clinical features, and can lead to progressive renal failure. It is primarily caused by mutations in the gene. This article reports the case of a 10-year-old male patient of Chinese descent who was incidentally found to have asymptomatic proteinuria during a routine health examination.
View Article and Find Full Text PDFHirudin Inhibits Pyroptosis to Alleviate Renal Fibrosis via the mTOR/HIF-1α Pathway.
J Interferon Cytokine Res
September 2025
Department of Nephrology, The First Affiliated Hospital of Guangxi University of Chinese Medicine, Guangxi, China.
Hirudin, a polypeptide extracted from medicinal leeches, has demonstrated potential in treating renal fibrosis. This study aimed to explore the underlying mechanisms by which Hirudin alleviates renal fibrosis. Renal fibrosis models were established using unilateral ureteral obstruction (UUO) surgery in rats and transforming growth factor-β (TGF-β)-induced HK-2 cells, followed by treatment with different concentrations of Hirudin.
View Article and Find Full Text PDF[ Granules ameliorate renal damage in MRL/lpr mice by inhibiting the MyD88/NF-κB pathway].
Nan Fang Yi Ke Da Xue Xue Bao
August 2025
First Affiliated Hospital of Anhui University of Chinese Medicine.
Objectives: To investigate the mechanism of (QJZ) for ameliorating renal damage in MRL/lpr mice.
Methods: With 6 female C57BL/6 mice as the normal control group, 30 female MRL/lpr mice were randomized into model group, QJZ treatment groups at low, moderate and high doses, and prednisone treatment group (6). After 8 weeks of treatment, the mice were examined for 24-h urine protein, creatinine and albumin levels, serum levels of IgG, complement 3 (C3), C4, anti-dsDNA, interferon γ (IFN‑γ) and interleukin 17 (IL-17).
Multimodal treatment approach with sunitinib, pembrolizumab, bevacizumab, sirolimus, and zoledronic acid for locally advanced clear cell renal cell carcinoma: a case report.
Croat Med J
August 2025
Mehrdad Payandeh, Internal Medicine Department, School of Medicine, Kermanshah University of Medical Sciences, Beheshti Blvd, 83VX+PCM, Kermanshah, Iran,
Locally advanced renal cell carcinoma (RCC) presents significant therapeutic challenges, particularly in resource-limited settings with restricted access to new therapies. This report describes a new exploratory multimodal therapeutic approach for a patient with locally advanced clear cell RCC (ccRCC) with adrenal and lymph node metastases. A 45-year-old woman presented with an incidentally discovered 9-cm mass in the left kidney, which was later diagnosed as grade-2 ccRCC with adrenal and lymph node involvement.
View Article and Find Full Text PDF