Browsing by Author "Yang, Yu"

Now showing 1 - 3 of 3
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    Distinct roles for ROCK1 and ROCK2 in the regulation of cell detachment
    (Springer Nature, 2013-02-07) Shi, Jianjian; Wu, Xiangbing; Surma, Michelle; Vemula, Sasidhar; Zhang, Lumin; Yang, Yu; Kapur, Reuben; Wei, Lei; Pediatrics, School of Medicine
    This study, using mouse embryonic fibroblast (MEF) cells derived from ROCK1(-/-) and ROCK2(-/-) mice, is designed to dissect roles for ROCK1 and ROCK2 in regulating actin cytoskeleton reorganization induced by doxorubicin, a chemotherapeutic drug. ROCK1(-/-) MEFs exhibited improved actin cytoskeleton stability characterized by attenuated periphery actomyosin ring formation and preserved central stress fibers, associated with decreased myosin light chain 2 (MLC2) phosphorylation but preserved cofilin phosphorylation. These effects resulted in a significant reduction in cell shrinkage, detachment, and predetachment apoptosis. In contrast, ROCK2(-/-) MEFs showed increased periphery membrane folding and impaired cell adhesion, associated with reduced phosphorylation of both MLC2 and cofilin. Treatment with inhibitor of myosin (blebbistatin), inhibitor of actin polymerization (cytochalasin D), and ROCK pan-inhibitor (Y27632) confirmed the contributions of actomyosin contraction and stress fiber instability to stress-induced actin cytoskeleton reorganization. These results support a novel concept that ROCK1 is involved in destabilizing actin cytoskeleton through regulating MLC2 phosphorylation and peripheral actomyosin contraction, whereas ROCK2 is required for stabilizing actin cytoskeleton through regulating cofilin phosphorylation. Consequently, ROCK1 and ROCK2 can be functional different in regulating stress-induced stress fiber disassembly and cell detachment.
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    Multi-omic profiling of clear cell renal cell carcinoma identifies metabolic reprogramming associated with disease progression
    (Springer Nature, 2024) Hu, Junyi; Wang, Shao-Gang; Hou, Yaxin; Chen, Zhaohui; Liu, Lilong; Li, Ruizhi; Li, Nisha; Zhou, Lijie; Yang, Yu; Wang, Liping; Wang, Liang; Yang, Xiong; Lei, Yichen; Deng, Changqi; Li, Yang; Deng, Zhiyao; Ding, Yuhong; Kuang, Yingchun; Yao, Zhipeng; Xun, Yang; Li, Fan; Li, Heng; Hu, Jia; Liu, Zheng; Wang, Tao; Hao, Yi; Jiao, Xuanmao; Guan, Wei; Tao, Zhen; Ren, Shancheng; Chen, Ke; Pathology and Laboratory Medicine, School of Medicine
    Clear cell renal cell carcinoma (ccRCC) is a complex disease with remarkable immune and metabolic heterogeneity. Here we perform genomic, transcriptomic, proteomic, metabolomic and spatial transcriptomic and metabolomic analyses on 100 patients with ccRCC from the Tongji Hospital RCC (TJ-RCC) cohort. Our analysis identifies four ccRCC subtypes including De-clear cell differentiated (DCCD)-ccRCC, a subtype with distinctive metabolic features. DCCD cancer cells are characterized by fewer lipid droplets, reduced metabolic activity, enhanced nutrient uptake capability and a high proliferation rate, leading to poor prognosis. Using single-cell and spatial trajectory analysis, we demonstrate that DCCD is a common mode of ccRCC progression. Even among stage I patients, DCCD is associated with worse outcomes and higher recurrence rate, suggesting that it cannot be cured by nephrectomy alone. Our study also suggests a treatment strategy based on subtype-specific immune cell infiltration that could guide the clinical management of ccRCC.
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    The value of enhanced CT scanning for predicting lymph node metastasis along the right recurrent laryngeal nerve in esophageal squamous cell carcinoma
    (AME, 2020-12) Li, Bin; Li, Baiwei; Jiang, Haoyao; Yang, Yang; Zhang, Xiaobin; Su, Yuchen; Hua, Rong; Gu, Haiyong; Guo, Xufeng; Ye, Bo; Yang, Yu; He, Yi; Sun, Yifeng; Piessen, Guillaume; Hochwald, Steven N.; Cuesta, Miguel A.; Birdas, Thomas J.; Li, Zhigang; Surgery, School of Medicine
    Background: The right recurrent laryngeal nerve (RRLN) is the region most prone to lymph node metastasis in esophageal squamous cell carcinoma (ESCC). Nodal involvement may be underestimated by traditional imaging prediction criteria, such as a short axis diameter of 10 mm. The purpose of this study was to determine a more accurate imaging criterion to guide clinical treatment strategy selection. Methods: The clinical data of 307 patients with thoracic ESCC who underwent surgery at Shanghai Chest Hospital between January 2018 and December 2018 were retrospectively analyzed. Utilizing 1-mm layer thickness enhanced computed tomography (CT), the RRLN lymph node short diameter (LNSD) size was measured. Univariate and multivariate analyses were performed to determine the risk factors for lymph node metastasis along the RRLN. Results: In our study, RRLN lymph node metastasis occurred in 60 (19.5%) patients and general lymph node metastasis occurred in 150 (48.9%) patients. Of the resected lymph nodes along the RRLN, 14.5% (121/832) were positive. Multivariate analysis identified LNSD [odds ratio (OR), 1.236] as an independent risk factor for RRLN lymph node metastasis. In CT evaluation, a short diameter of 6.5 mm in the RRLN lymph nodes is a critical predictor of metastasis at this site (sensitivity =50%, specificity =83.4%) and a larger short diameter was associated with a higher risk of metastasis (P<0.001). Conclusions: A 6.5 mm cutoff in LNSD can be applied to clinically predict lymph node metastasis in the RRLN region for patients with ESCC.