aKNNO: single-cell and spatial transcriptomics clustering with an optimized adaptive k-nearest neighbor graph DOI Creative Commons
Jia Li, Yu Shyr, Qi Liu

et al.

Genome biology, Journal Year: 2024, Volume and Issue: 25(1)

Published: Aug. 1, 2024

Abstract Typical clustering methods for single-cell and spatial transcriptomics struggle to identify rare cell types, while approaches tailored detect types gain this ability at the cost of poorer performance grouping abundant ones. Here, we develop aKNNO simultaneously based on an adaptive k -nearest neighbor graph with optimization. Benchmarking 38 simulated 20 datasets demonstrates that identifies both more accurately than general specialized methods. Using only gene expression maps cells precisely compared integrative approaches.

Language: Английский

Downstream Targets of VHL/HIF-α Signaling in Renal Clear Cell Carcinoma Progression: Mechanisms and Therapeutic Relevance DOI Open Access
Sonia Mazumder, Paul J. Higgins, Rohan Samarakoon

et al.

Cancers, Journal Year: 2023, Volume and Issue: 15(4), P. 1316 - 1316

Published: Feb. 19, 2023

The clear cell variant of renal carcinoma (ccRCC) is the most common epithelial malignancy and responsible for deaths from kidney cancer. Patients carrying inactivating mutations in Von Hippel-Lindau (VHL) gene have an increased proclivity to develop several types tumors including ccRCC. Normally, Hypoxia Inducible Factor alpha (HIF-α) subunits HIF heterodimeric transcription factor complex are regulated by oxygen-dependent prolyl-hydroxylation, VHL-mediated ubiquitination proteasomal degradation. Loss pVHL function results elevated levels HIF-α due stability, leading RCC progression. While HIF-1α acts as a tumor suppressor, HIF-2α promotes oncogenic potential driving progression metastasis through activation hypoxia-sensitive signaling pathways overexpression target genes. One strategy suppress ccRCC aggressiveness directed at inhibition associated molecular proliferation, angiogenesis, metastasis. Indeed, clinical pre-clinical data demonstrated effectiveness targeted therapy attenuating This review focuses on involved genes (cyclin D, c-Myc, VEGF-a, EGFR, TGF-α, GLUT-1) that confer downstream VHL-HIF-2α axis Discussed well current treatment options (including receptor tyrosine kinase inhibitors such sunitinib), medical challenges (high prevalence time diagnosis, refractory nature advanced disease options), scientific future directions.

Language: Английский

Citations

41
Single-Cell RNA Sequencing in Ovarian Cancer: Current Progress and Future Prospects DOI
Zhi Xiong Chong

Progress in Biophysics and Molecular Biology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

1
Single-cell transcriptomic analysis reveals CD8 + T cell heterogeneity and identifies a prognostic signature in cervical cancer DOI Creative Commons
Rongbin Zhou,

Yuli Xie,

Zuheng Wang

et al.

BMC Cancer, Journal Year: 2025, Volume and Issue: 25(1)

Published: March 18, 2025

Abstract Background In recent years, immunotherapy has made significant progress. However, the understanding of heterogeneity and function T cells, particularly CD8 + in cervical cancer (CESC) microenvironment remains insufficient. We aim to characterize heterogeneity, developmental trajectory, regulatory network, intercellular communication cells squamous cell carcinoma construct a prognostic risk model based on transcriptomic characteristics cells. Methods integrated single-cell RNA sequencing data from CESC tumor samples with bulk transcriptome TCGA GEO databases. identified subsets microenvironment, revealing interactions between other types through analysis. Pseudotime trajectory analysis revealed dynamic transcriptional regulation during differentiation functional acquisition processes. constructed network for identifying key transcription factors. Based cell-related genes, comprising eight core genes was developed validated using machine learning. Results four distinct subsets, namely progenitor, intermediate, proliferative, terminally differentiated, each exhibiting unique properties. interact macrophages different ligand-receptor networks, including CCL-CCR signaling pathway costimulatory molecules. Sorafenib as potential immunotherapeutic drug screening. Experimental validation demonstrated that sorafenib enhances cytotoxicity by increasing secretion IFN-γ TNF-α, thereby significantly inhibiting invasiveness survival Conclusions Our study provides valuable insights into diversity CESC. demonstrate signature may serve tool stratification patients Additionally, our finding suggests could be promising therapeutic candidate improving antitumor immunity this patient population.

Language: Английский

Citations

1
Vascular development, remodeling and maturation DOI
Jessica Furtado, Anne Eichmann

Current topics in developmental biology/Current Topics in Developmental Biology, Journal Year: 2024, Volume and Issue: unknown, P. 344 - 370

Published: Jan. 1, 2024

Language: Английский

Citations

6
Pan-cancer integrative analyses dissect the remodeling of endothelial cells in human cancers DOI Creative Commons
Jinhu Li, Dongfang Wang, Fei Tang

et al.

National Science Review, Journal Year: 2024, Volume and Issue: 11(9)

Published: July 10, 2024

ABSTRACT Therapeutics targeting tumor endothelial cells (TECs) have been explored for decades, with only suboptimal efficacy achieved, partly due to an insufficient understanding of the TEC heterogeneity across cancer patients. We integrated single-cell RNA-seq data 575 patients from 19 solid types, comprehensively charting phenotypic diversities. Our analyses uncovered underappreciated compositional and functional in TECs a pan-cancer perspective. Two subsets, CXCR4+ tip SELE+ veins, represented prominent angiogenic proinflammatory phenotypes TECs, respectively. They exhibited distinct spatial organization patterns, compared adjacent non-tumor tissues, tissue showed increased prevalence cells, yet veins depleted. Such characteristics underlie their differential associations response anti-angiogenic therapies immunotherapies. integrative resources findings open new avenues understand clinically intervene vasculature.

Language: Английский

Citations

6
Regulation of tumor angiogenesis by the crosstalk between innate immunity and endothelial cells DOI Creative Commons
S B Ebeling, Anita Kowalczyk, Diego Pérez-Vázquez

et al.

Frontiers in Oncology, Journal Year: 2023, Volume and Issue: 13

Published: May 10, 2023

Endothelial cells and immune are major regulators of cancer progression prognosis. cell proliferation angiogenesis required for providing nutrients oxygen to the nascent tumor infiltration is dependent on endothelial activation. Myeloid innate lymphocytes have an important role in shaping microenvironment by crosstalking with structural cells, including cells. Innate can modulate activation functions and, turn, expression adhesion molecules affect extravasation. However, mechanisms underlying this bidirectional crosstalk not fully understood. In review, we will provide overview current knowledge pathways regulating between during discuss their potential contribution development novel anti-tumor therapeutic approaches.

Language: Английский

Citations

16
It is better to light a candle than to curse the darkness: single-cell transcriptomics sheds new light on pancreas biology and disease DOI Open Access
Amelia Cephas, William L. Hwang, Anirban Maitra

et al.

Gut, Journal Year: 2023, Volume and Issue: 72(6), P. 1211 - 1219

Published: March 30, 2023

Recent advances in single-cell RNA sequencing and bioinformatics have drastically increased our ability to interrogate the cellular composition of traditionally difficult study organs, such as pancreas. With advent these technologies approaches, field has grown, just a few years, from profiling pancreas disease states identifying molecular mechanisms therapy resistance pancreatic ductal adenocarcinoma, particularly deadly cancer. Single-cell transcriptomics related spatial approaches identified previously undescribed epithelial stromal cell types states, how populations change with progression, potential action which will serve basis for designing new therapeutic strategies. Here, we review recent literature on transcriptomic changed understanding biology progression.

Language: Английский

Citations

12
The Role of Extracellular Vesicles in the Treatment of Prostate Cancer DOI
Cong Hu, Qi Chen, Tianyang Wu

et al.

Small, Journal Year: 2024, Volume and Issue: unknown

Published: April 19, 2024

Prostate cancer (PCa) has become a public health concern in elderly men due to an ever-increasing number of estimated cases. Unfortunately, the available treatments are unsatisfactory because lack durable response, especially advanced disease states. Extracellular vesicles (EVs) lipid-bilayer encircled nanoscale that carry numerous biomolecules (e.g., nucleic acids, proteins, and lipids), mediating transfer information. The past decade witnessed wide range EV applications both diagnostics therapeutics. First, EV-based non-invasive liquid biopsies provide biomarkers various clinical scenarios guide treatment; EVs can facilitate grading staging patients for appropriate treatment selection. Second, play pivotal role pathophysiological processes via intercellular communication. Targeting key molecules involved EV-mediated tumor progression proliferation, angiogenesis, metastasis, immune escape, drug resistance) is potential approach curbing PCa. Third, promising carriers. Naïve from sources engineered delivery systems have paved way development new modalities. This review discusses recent advancements application therapies highlights functional materials as novel interventions

Language: Английский

Citations

4
Conserved patterns of transcriptional dysregulation, heterogeneity, and cell states in clear cell kidney cancer DOI Creative Commons
Olivia Lombardi, Ran Li, Faiz Jabbar

et al.

Cell Reports, Journal Year: 2025, Volume and Issue: 44(1), P. 115169 - 115169

Published: Jan. 1, 2025

Language: Английский

Citations

0
Unveiling the immunomodulatory dance: endothelial cells’ function and their role in non-small cell lung cancer DOI Creative Commons
Sophia Daum,

Lilith Decristoforo,

Mira Mousa

et al.

Molecular Cancer, Journal Year: 2025, Volume and Issue: 24(1)

Published: Jan. 16, 2025

The dynamic interactions between tumor endothelial cells (TECs) and the immune microenvironment play a critical role in progression of non-small cell lung cancer (NSCLC). In general, exhibit diverse immunomodulatory properties, influencing recruitment, antigen presentation, regulation checkpoint expression. Understanding multifaceted roles TECs as well assigning specific functional hallmarks to various TEC phenotypes offer new avenues for targeted development therapeutic interventions, particularly context advanced immunotherapy anti-angiogenic treatments. This review provides insights into complex interplay system NSCLC including discussion potential optimized opportunities.

Language: Английский

Citations

0