Article
Medicine, Research & Experimental
Philipp Seidel, Anne Rubarth, Kyra Zodel, Asin Peighambari, Felix Neumann, Yannick Federkiel, Hsin Huang, Rouven Hoefflin, Mojca Adlesic, Christian Witt, David J. Hoffmann, Patrick Metzger, Ralph K. Lindemann, Frank T. Zenke, Christoph Schell, Melanie Boerries, Dominik von Elverfeldt, Wilfried Reichardt, Marie Follo, Joachim Albers, Ian J. Frew
Summary: This study identifies ATR inhibition as a potential therapeutic option for ccRCC, showing that the drug M4344 induces antiproliferative effects in ccRCC cells by inhibiting the DNA damage-sensing kinase ATR. The combination of M4344 with chemotherapeutic drugs or a poly(ADP-ribose) polymerase inhibitor demonstrates better efficacy in both mouse and human ccRCC cells.
Article
Oncology
Jiale Zhou, Junyun Wang, Wen Kong, Jin Zhang, Xiaorong Wu, Jiwei Huang, Junhua Zheng, Yonghui Chen, Wei Zhai, Wei Xue
Summary: This study found that mccRCC patients with DDR and VHL alterations are more likely to benefit from first-line VEGF-TKI systemic therapy. Furthermore, a three-cluster prognostic model based on gene expression can predict progression-free survival and objective response rate, which is correlated with immune cell infiltration.
Article
Biochemistry & Molecular Biology
Jiefeng Yang, Li Luo, Chongyu Zhao, Xiyuan Li, Zimo Wang, Ziwei Zeng, Xin Yang, Xiaobin Zheng, Haiqing Jie, Liang Kang, Shujuan Li, Shuang Liu, Chi Zhou, Huashan Liu
Summary: Inactive von Hippel-Lindau (VHL) plays a role in promoting the progression of clear cell renal cell carcinoma (ccRCC) by triggering histone lactylation and forming an oncogenic positive feedback loop with PDGFR beta signaling. Targeting histone lactylation and PDGFR beta can effectively inhibit the growth and metastasis of ccRCC.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2022)
Article
Multidisciplinary Sciences
Johannes C. van der Mijn, Kristian B. Laursen, Leiping Fu, Francesca Khani, Lukas E. Dow, Dawid G. Nowak, Qiuying Chen, Steven S. Gross, David M. Nanus, Lorraine J. Gudas
Summary: Genetically engineered mouse models (GEMMs) are important for cancer research and therapy development. In this study, researchers developed two GEMMs using inducible CRISPR-Cas9 systems to simulate common chromosome deletions in kidney cancer. The models induced somatic mutations in the kidneys but did not cause tissue transformation. Further research is needed.
SCIENTIFIC REPORTS
(2023)
Article
Oncology
Claudia Manini, Estibaliz Lopez-Fernandez, Jose Lopez
Summary: Intratumor heterogeneity (ITH) is a common event in malignant tumors and is a major cause of therapeutic failures in modern oncology. Clear cell renal cell carcinoma (CCRCC) exemplifies ITH. To accurately detect ITH, appropriate tumor sampling is necessary. We propose a personalized multisite tumor sampling (pMSTS) strategy based on the regionalization patterns of ITH, with a focus on sampling the high-ITH peripheral zones of the tumor.
Article
Biochemistry & Molecular Biology
Magdalena Chrabanska, Nikola Szweda-Gandor, Bogna Drozdzowska
Summary: This study found that two single nucleotide polymorphisms (SNPs), rs779805 and rs1642742, located in the VHL gene are associated with the occurrence of clear cell renal cell carcinoma (ccRCC). These SNPs were not significantly associated with susceptibility or survival of ccRCC, but were associated with tumor size, which is an important prognostic indicator for renal cancer. Therefore, these SNPs may serve as genetic tumor markers for molecular diagnostics in ccRCC patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Oncology
Borivoj Golijanin, Kamil Malshy, Sari Khaleel, Galina Lagos, Ali Amin, Liang Cheng, Dragan Golijanin, Anthony Mega
Summary: Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney cancer, and its pathogenesis is mainly caused by biallelic loss of the tumor suppressor gene VHL. Dysfunctional degradation of HIF due to VHL loss leads to overaccumulation of HIF, resulting in the activation of genes responsible for cell survival and proliferation in ccRCC. Previous therapies have targeted downstream effectors of HIF, but there is now a focus on interfering with upstream targets.
CANCER TREATMENT REVIEWS
(2023)
Article
Oncology
Jiwei Huang, Wen Cai, Biao Cai, Wen Kong, Wei Zhai, Jin Zhang, Yonghui Chen, Shiqing Chen, Yuezong Bai, Yiran Huang, Wei Xue
Summary: The study investigated the molecular features of Chinese ccRCC patients, revealing differences in mutation frequencies of genes like VHL and PBRM1 compared to the TCGA database. Some patients showed positive PD-L1 expression, while a small portion carried pathogenic or likely pathogenic germline mutations.
FRONTIERS IN ONCOLOGY
(2021)
Article
Oncology
Wuping Yang, Jingcheng Zhou, Kenan Zhang, Lei Li, Yawei Xu, Kaifang Ma, Haibiao Xie, Lin Cai, Yanqing Gong, Kan Gong
Summary: This study identified 10 VHL-related lncRNAs in ccRCC tissues and revealed their down-regulation. High expression of these lncRNAs was associated with longer overall and disease free survival, with FGD5-AS1 showing potential as a novel biomarker for ccRCC. Additionally, DNA hypermethylation was implicated in the decreased expression of FGD5-AS1.
Review
Oncology
Sonia Mazumder, Paul J. Higgins, Rohan Samarakoon
Summary: Mutations in the VHL gene contribute to the development of renal cell carcinoma, particularly the clear cell variant. HIF-2 alpha plays a crucial role in promoting tumor progression and metastasis in these cases. Inhibiting HIF-2 alpha and its associated molecular pathways can be an effective strategy to suppress the aggressiveness of ccRCC.
Article
Biochemistry & Molecular Biology
Junhui Hu, Desmond J. Smith, Lily Wu
Summary: This study characterized the biochemical activity, transcriptomic hypoxia signature, and biological functions of the L169P variant in the von Hippel-Lindau (VHL) tumor suppressor gene. The results showed that the L169P variant has comparable protein stability, ability to degrade HIF1 alpha and HIF2 alpha, and ability to regulate hypoxia gene expression as the wildtype VHL. Additionally, the L169P variant exhibited similar suppression of ccRCC tumor cell growth compared to the wildtype VHL.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Ufuk Unal, Gulsah Cecener, Havva Tezcan Unlu, Berna Aytac Vuruskan, Ecem Efendi Erdem, Unal Egeli, Hulya Ozturk Nazlioglu, Onur Kaygisiz, Berrin Tunca, Hakan Vuruskan
Summary: This study found that differences in the expression levels of miR-223 have the potential to serve as biomarkers for determining poor prognosis in ccRCC.
MOLECULAR BIOLOGY REPORTS
(2022)
Article
Multidisciplinary Sciences
Ping Wang, Xu Pei, Xiao-Ping Yin, Jia-Liang Ren, Yun Wang, Lu-Yao Ma, Xiao-Guang Du, Bu-Lang Gao
Summary: This study aimed to evaluate the effect of predictive radiomic models in distinguishing ccRCC from non-ccRCC using CT imaging data, showing promise in augmenting radiological diagnosis in renal cancer, particularly in differentiating subtypes. The radiomic models performed well in discriminating RCC subtypes, with RF, SVM, and LR models showing high AUC values and sensitivities in the testing set compared to radiologist diagnosis.
SCIENTIFIC REPORTS
(2021)
Review
Cell Biology
Lauren E. Langbein, Rayan El Hajjar, William Y. Kim, Haifeng Yang
Summary: In clear cell renal cell carcinoma, the VHL/HIF axis is the foundation for tumorigenesis and is influenced by secondary mutations in tumor suppressor genes. The negative feedback loop plays a crucial role in tumor growth, and its impairment by secondary mutations suggests that activation of ISGF3 could be an effective treatment for ccRCC.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2022)
Review
Genetics & Heredity
Maria F. Czyzyk-Krzeska, Julio A. Landero Figueroa, Shuchi Gulati, John T. Cunningham, Jarek Meller, Behrouz ShamsaeI, Bhargav Vemuri, David R. Plas
Summary: Personalized medicine utilizes multiple omics platforms and environmental factors to guide treatments for clear cell renal carcinoma. Different genetic subtypes have varying prognoses, with altered metabolism being a key feature of the disease. Single-cell combined multi-omics approaches will provide deeper insights into ccRCC progression and lead to the design of specific signatures for better clinical outcomes.
Article
Biochemistry & Molecular Biology
Ping He, Cheng Zhang, Yan Ji, Meng-Kai Ge, Yun Yu, Na Zhang, Shuo Yang, Jian-Xiu Yu, Shao-Ming Shen, Guo-Qiang Chen
Summary: SNHG8, a chromatin-localized lncRNA, interacted and phase separated with histone H1 variants. It showed stronger binding ability to H1 proteins than linker DNA, leading to increased chromatin condensation and epithelial cell differentiation.
CELL DEATH AND DIFFERENTIATION
(2022)
Article
Pharmacology & Pharmacy
Xin-Ping Zhu, Gao-Chao Han, Qiang Chen, Zheng-Yan Zhang, Li-Shun Wang, Bo Zhang
Summary: This study found that in the Chinese population, fatty liver has a higher predictive value for hypertension and its complications compared to BMI, serving as a more sensitive early warning indicator for hypertension and its complications.
CLINICAL AND EXPERIMENTAL HYPERTENSION
(2022)
Article
Pathology
Zheng-Yan Zhang, Shi-Long Zhang, Hui-Ling Chen, Yu-Qin Mao, Chao-Yue Kong, Zhan-Ming Li, Li-Shun Wang, Ming Ma, Bing Han
Summary: The study found that the EGR1 protein levels are significantly decreased in ccRCC cancer tissues, and patients with low EGR1 expression are more prone to exhibit metastasis and a poor prognosis. EGR1 serves as an independent prognostic factor for patients with ccRCC.
PATHOLOGY RESEARCH AND PRACTICE
(2021)
Article
Biochemistry & Molecular Biology
Zhi Pang, Xinran Dong, Huayun Deng, Chengzhi Wang, Xiaodong Liao, Chunhua Liao, Yahui Liao, Weidong Tian, Jinke Cheng, Guoqiang Chen, Haiying Yi, Lei Huang
Summary: Aberrant overexpression of MUC1 and HER2 is associated with breast cancer, and their concomitant expression leads to worse clinical outcome. In a mouse model, coexpression of Her2 and MUC1-CD promotes mammary tumor development and induces changes in tumor lineage plasticity and downregulation of tricarboxylic acid cycle genes. Furthermore, MUC1 enhances the Her2 signaling pathway by inducing Her2/Egfr dimerization.
Article
Multidisciplinary Sciences
Xue Chen, Yanyan Xu, Qidi Chen, Heng Zhang, Yu Zeng, Yan Geng, Lei Shen, Fubin Li, Lei Chen, Guo-Qiang Chen, Chuanxin Huang, Junling Liu
Summary: PTEN-deficient platelets promote autoimmunity in mouse models through excessive activation of T-FH cells and systemic autoimmune pathology.
NATURE COMMUNICATIONS
(2022)
Article
Gastroenterology & Hepatology
Shi-Long Zhang, Bing Han, Yu-Qin Mao, Zheng-Yan Zhang, Zhan-Ming Li, Chao-Yue Kong, You Wu, Guo-Qiang Chen, Li-Shun Wang
Summary: The gut microbiota plays a critical role in cancer immunotherapy outcomes. The study found that the gut microbiota from healthy individuals enhances sensitivity to anti-PD-1 in colorectal cancer tumor-bearing mice, while gut microbiota from CRC patients does not have the same effect. Lactobacillus was identified as a key species significantly increased in mice with a good response to anti-PD-1, and it was correlated with anti-tumor immunity. The novel strain L. paracasei sh2020 demonstrated notable anti-tumor immunity and enhanced gut barrier function, suggesting its potential as an effective way to promote the effect of anti-PD-1 in clinical practice.
Article
Immunology
Yifan Zhu, Yuyan Tang, Haidong He, Ping Hu, Weiqian Sun, Meiping Jin, Lishun Wang, Xudong Xu
Summary: This study explores the changes in gut microbiota between ESRD patients with different responsiveness to EPO treatment and finds significant differences in gut microbiota composition between poor-response and good-response patients. By analyzing specific genera of gut microbiota, the occurrence of EPO hyporesponsiveness (EH) can be predicted accurately. Furthermore, certain genera of gut microbiota have a protective effect against EH. These findings provide new insights into the pathogenesis of renal anemia and suggest the potential role of gut microbiota in EPO treatment.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Microbiology
Hui Jing, Qimeng Chang, Yayun Xu, Jianfa Wang, Xubo Wu, Jiating Huang, Lishun Wang, Ziping Zhang
Summary: The gut microbiota of older adults exacerbates acute pancreatitis during both the early and recovery stages, and is characterized by a decline in antimicrobial peptides.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Nutrition & Dietetics
Chao-Yue Kong, Zhan-Ming Li, Hui-Ling Chen, Yu-Qin Mao, Bing Han, Jian-Jun Guo, Li-Shun Wang
Summary: This study investigated the benefits of a novel dietary treatment in mice with MetS. The results showed that the CR-YD diet had a better therapeutic effect in mice with HFD-induced MetS compared to calorie restriction alone.
JOURNAL OF NUTRITION
(2022)
Article
Gastroenterology & Hepatology
Zhan-Ming Li, Chao-Yue Kong, Yu-Qin Mao, Jia-Ting Huang, Hui-Ling Chen, Bing Han, Li-Shun Wang
Summary: This study reveals that the antibiotic ampicillin (Amp) may exacerbate acute liver injury (ALI) caused by acetaminophen (APAP) and demonstrates the influence of gut microbiota on this process. The results show that Amp exposure reduces the diversity and alters the composition of gut microbiota, leading to worsened liver damage caused by APAP. This effect is proven to be microbiota-related through fecal microbiota transplantation. Additionally, supplementation of lactobacillus, especially Lactobacillus rhamnosus, can reverse the aggravated liver injury induced by APAP and Amp.
LIVER INTERNATIONAL
(2023)
Article
Gastroenterology & Hepatology
Yayun Xu, Jianfa Wang, Xubo Wu, Hui Jing, Shilong Zhang, Zhiqiu Hu, Longhua Rao, Qimeng Chang, Lishun Wang, Ziping Zhang
Summary: Post-cholecystectomy diarrhea (PCD) is a common condition among outpatients who have undergone cholecystectomy, and it is associated with changes in gut microbiota. In this study, a humanized gut microbiome mouse model was used to investigate the effects of altered fecal bacteria on diarrhea. The researchers found that PCD mice transplanted with fecal microbiome from PCD patients had increased gastrointestinal motility and fecal water content compared to mice with fecal microbiome from NonPCD patients and healthy controls. They also identified an enrichment of tryptophan metabolism in the gut microbiota of PCD mice. Additionally, they discovered elevated levels of serotonin and increased expression of 5-HT receptors in the colon of PCD mice, which were associated with diarrhea. The researchers also found that microbial secondary bile acids were responsible for stimulating serotonin levels in the colon and increasing colon motility. Blocking the bile acid-mediated signaling pathway alleviated the symptoms of PCD. These findings suggest that altered gut microbiota and bile acid metabolism play a role in the development of PCD.
Article
Microbiology
Chao-Yue Kong, Yi-Qin Yang, Bing Han, Hui-Ling Chen, Yu-Qin Mao, Jia-Ting Huang, Li-Shun Wang, Zhan-Ming Li
Summary: In this study, the role of gut microbiota in lactation mastitis was investigated using a microbiota-humanized mouse model. The results showed that lactation mastitis patients had reduced gut microbiota diversity and dysbiosis. Fecal microbiota transplantation from lactation mastitis patients induced mastitis in antibiotic-treated mice. This study demonstrates that dysbiotic gut microbiota contributes to the pathogenesis of lactation mastitis.
FRONTIERS IN MICROBIOLOGY
(2023)
Editorial Material
Oncology
Lishun Wang, Hanchen Xu, Yadi Wu
FRONTIERS IN ONCOLOGY
(2023)
Article
Endocrinology & Metabolism
Yu-Qin Mao, Jia-Ting Huang, Shi-Long Zhang, Chao Kong, Zhan-Ming Li, Hui Jing, Hui-Ling Chen, Chao-Yue Kong, Sheng-Hui Huang, Pei-Ran Cai, Bing Han, Li-Shun Wang
Summary: The study reveals that caloric restriction increases the presence of Bifidobacterium bifidum in the intestine, which ultimately inhibits tumor development in mice. Caloric restriction and intermittent fasting, without causing malnutrition, have been found to reduce the risk of cancer. Additionally, both caloric restriction and intermittent fasting can alter the composition of the gut microbiota. It is shown in this study that caloric restriction, but not intermittent fasting, protects against subcutaneous MC38 tumor formation in female mice through a mechanism involving the gut microbiota. These findings highlight the oncological significance of modulating the gut taxonomic composition in tumor growth and cancer immunosurveillance.
Article
Medicine, Research & Experimental
Shi-Long Zhang, Yu-Qin Mao, Zheng-Yan Zhang, Zhan-Ming Li, Chao-Yue Kong, Hui-Ling Chen, Pei-Ran Cai, Bing Han, Tao Ye, Li-Shun Wang
Summary: Pectin enhances the efficacy of anti-PD-1 mAb in colorectal cancer by regulating T cell infiltration in the tumor microenvironment, potentially mediated by the metabolite butyrate. This effect is dependent on gut microbiota and can even be effective in patients who are resistant to anti-PD-1 therapy.
