Soluble CD137 and risk of hepatocellular carcinoma: nested case–control studies in cohorts in Shanghai and Singapore
Background
The majority of hepatocellular carcinoma (HCC) cases occur in the presence of cirrhosis. Biomarkers of cirrhosis-associated immune dysfunction such as CD8+ T cell cytokines could aid HCC risk assessment. Methods
CD8+ T cell cytokines were determined in pre-diagnostic serum in two studies including 315 HCC case–control pairs in the Shanghai Cohort Study (SCS) and 197 pairs in the Singapore Chinese Health Study (SCHS). Conditional logistic regression was used to estimate odds ratio (OR) and 95% confidence interval (CI) for HCC with levels of five cytokines—soluble CD137 (sCD137), soluble Fas (sFas), perforin, macrophage inflammatory protein 1-beta (MIP-1β), and tumour necrosis factor alpha (TNF-α). Results
sCD137 levels were significantly higher in HCC cases than controls in both cohorts (Ps < 0.001). Compared with the lowest quartile, multivariable-adjusted ORs (95% CI) of HCC for the highest sCD137 quartile were 3.79 (1.73, 8.30) in the SCS and 3.49 (1.44, 8.48) in the SCHS. The sCD137-HCC association was independent of hepatitis B seropositivity and follow-up time. No other cytokine was consistently associated with HCC risk. Conclusion
sCD137 was associated with higher risk of HCC in two studies nested in general population cohorts. sCD137 may be a long-term risk marker of HCC development. Data availability
The data that support the findings of this study are available from the corresponding author upon reasonable request. Code availability
The computer code that support the findings of this study is available from the corresponding author upon reasonable request. References
Ferlay J, Colombet M, Soerjomataram I, Parkin DM, Piñeros M, Znaor A, et al. Cancer statistics for the year 2020: an overview. Int J Cancer. 2021. https://doi.org/10.1002/ijc.33588 . Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394–424. Acknowledgements
We thank the Singapore Cancer Registry for the identification of incident cancer cases among participants of the Singapore Chinese Health Study and Siew-Hong Low of the National University of Singapore for supervising the fieldwork of the Singapore Chinese Health Study. We also thank Ms. Xue-Li Wang of the Shanghai Cancer Institute for supervising the field work of the Shanghai Cohort Study and the Shanghai Cancer Registry for assistance with identification of cancer outcomes in the Shanghai Cohort Study. This project used the UPMC Hillman Cancer Center Cancer Biomarkers Facility: Luminex Core Laboratory. Funding
The Shanghai Cohort Study was supported by the National Institutes of Health (NIH) of the United States (grants # R01CA043092, R01CA144034, and UM1CA182876), and the Singapore Chinese Health Study was supported by NIH (grants # R01CA080205, R01CA144034, and UM1CA182876). The current work was also partially supported by the NIH grants # R01CA255809 and P30CA047904. CET is supported through a NIH training grant (grant # T32 CA186873). The content is solely the responsibility of the authors and does not necessarily represent the official views of NIH. Author information
Ethics approval and consent to participate
The Shanghai Cohort Study has been approved by the Institutional Review Boards of the Shanghai Cancer Institute and the University of Pittsburgh. The Singapore Chinese Health Study has been approved by the Institutional Review Boards of the National University of Singapore and the University of Pittsburgh. Informed consent was obtained from all participants. The present study has been approved by the University of Pittsburgh Human Research Protection Office and was conducted in accordance with the Declaration of Helsinki. Additional information
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Soluble CD137 and risk of hepatocellular carcinoma: nested case–control studies in cohorts in Shanghai and Singapore

Association Between Triglyceride-Glucose Index and Risk of Metabolic Dysfunction-Associated Fatty Liver Disease: A Cohort Study

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SHANGHAI, Aug. 2, 2022 /PRNewswire/ -- CARsgen Therapeutics Holdings Limited (Stock Code: 2171.HK), a company focused on innovative CAR T-cell therapies for the treatment of hematologic malignancies and solid tumors, announces that Dr. Hua Jiang ("Dr. Jiang") has been appointed as Executive Director of the Company. Hua Jiang, MD, PhD
Dr. Jiang has about 18 years of working experiences in the field of cancer biotherapy. She currently serves as Vice President of Early Discovery of CARsgen, responsible for formulating the strategy of early discovery and the construction of R&D pipeline. Dr. Jiang joined the Company in April 2021 as Senior Director of Immune Cell Research and Development Department, responsible for the research work of Immune Cell Research and Development and Preclinical Pharmacology. Dr. Jiang has contributed significantly to the early research, technology platform development, and innovative products development in CARsgen. Prior to joining the Company, from July 2007 to April 2021, Dr. Jiang worked at Shanghai Cancer Institute, responsible for the research and development of antibody and CAR T cells, as well as the related mechanisms. Dr. Jiang was a professor at Shanghai Cancer Institute and a doctoral supervisor at Shanghai Jiao Tong University School of Medicine. Dr. Jiang has published more than 20 SCI papers in journals such as Journal of the National Cancer Institute, Clinical Cancer Research, Molecular Therapy, etc. She is the first author to publish the world's first CLDN18.2 CAR T and first EGFR/EGFRvIII CAR T papers and the co-corresponding author to publish the world's first paper on the combination therapy of small molecule and CAR T cells for the treatment of solid tumors. Dr. Jiang earned her Bachelor's degree in Clinical Medicine from Jining Medical College in 2001. She obtained Master's degree in Pathogen Biology from Shandong University in 2004 and Ph.D. in Pathogen Biology from Fudan University in 2007. Dr. Zonghai Li, Founder, Chairman of the Board, Chief Executive Officer, and Chief Scientific Officer of CARsgen, added, "On behalf of the Board, I would like to congratulate Dr. Jiang to be appointed as the Executive Director. Dr Jiang has rich experiences in cancer research and product development, particularly in the field of CAR T-cell therapies. As the Executive Director of the Board, Dr Jiang will contribute to the diversity of the Board and will continue to help us developing innovative and differentiated CAR T products for cancer patients worldwide." Dr. Hua Jiang, Executive Director, Vice President of Early Discovery of CARsgen, said, "I am pleased to become a member of the Board and would like to thank the Board for the recognition and trust. I will spare no efforts to continue working with colleagues in CARsgen to develop innovative products for cancer patients and make cancer curable." About CARsgen Therapeutics Holdings Limited
CARsgen is a biopharmaceutical company with operations in China and the U.S. and is focused on innovative CAR T-cell therapies for the treatment of hematologic malignancies and solid tumors. The Company has built an integrated cell therapy platform with in-house capabilities that span target discovery, antibody development, clinical trials, and commercial-scale manufacturing. CARsgen has internally developed novel technologies and a product pipeline with global rights to address major challenges of CAR T-cell therapies, such as improving the safety profile, enhancing the efficacy in treating solid tumors and reducing treatment costs. The Company's vision is to become a global biopharmaceutical leader that brings innovative and differentiated cell therapies to cancer patients worldwide and makes cancer curable. Contact Us
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08:50 EDT
CARsgen Appoints Dr. Hua Jiang as Executive Director

Kai Wang,1,2 Yuzhong Li,3 Xiaowei Wang,4 Jianpeng Jiao,4 Ying Li,3 Wenyue Gu,5 Xiaofei Liang2,6
1Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences and Shanghai Public Health Clinical Center, Shanghai Medical College, Fudan University, Shanghai 200032, People’s Republic of China; 2State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200032, People’s Republic of China; 3Department of Clinical Laboratory, Second Affiliated Hospital of Dalian Medical University, Dalian 116023, People’s Republic of China; 4Department of Traditional Chinese Medicine, Changzheng Hospital, Shanghai 200001, People’s Republic of China; 5Department of Pathology, Yancheng Hospital Affiliated Southeast University, Yancheng, Jiangsu 224000, People’s Republic of China; 6Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai 200240, People’s Republic of China
Correspondence: Ying Li; Xiaofei Liang Email dyeyly@163.com; xfliang2019@163.com
Purpose: The aim of this study was to develop an avidin-modified macromolecular lipid magnetic sphere and its application in differential diagnosis of liver disease and liver cancer. Materials and Methods: Lectin-modified macromolecular lipid magnetic spheres were prepared by thin-film hydration method using lentil lectin derivatives (LCA-HQ) and cholesterol as raw materials. Alpha-fetoprotein variants (AFP-L3) in serum from healthy people, liver disease and liver cancer patients were isolated using the prepared lectin-modified macromolecular lipid magnetic spheres, and alpha-fetoprotein (AFP) and AFP-L3 were detected by fully automatic time-resolved fluorescence immunoassay. Results: The lectin polymer lipid magnetic sphere prepared in this study was superparamagnetic and encapsulated by a lectin derivative. There was no significant difference in the recovery rate of AFP-L3 between avidin magnetic ball-automatic time-resolved fluorescence immunoassay and manual micro-affinity column method (p> 0.05). We found that AFP-L3 can be used as a differential indicator between liver cancer and liver disease. The positive rate of AFP and AFP-L3 in liver cancer patients was higher than that in healthy people and liver disease patients (p< 0.001). The AUC (95% CI) of AFP and AFP-L3 were 0.743 ± 0.031 and 0.850 ± 0.024, respectively. AFP-L3 AUC value is greater than AFP; therefore, AFP-L3 distinguishes liver cancer more accurately, and the difference is statistically different, p< 0.05. Conclusion: We proposed a novel method for integration of the lectin polymer lipid magnetic spheres and time-resolved fluorescence immunoassay that enables simple, accurate and rapid determination of AFP-L3 in clinical samples. To be noted, fully automatic time-resolved fluorescence immunoassay compared with the commonly used techniques in clinical practice, the measurement procedure is simple and is expected to be used for the detection and accurate diagnosis of liver cancer. Keywords: liver cancer, alpha-fetoprotein, AFP, alpha-fetoprotein variant, AFP-L3, magnetic sphere, lens culinaris agglutinin, LCA
This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License . By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms .

Automatic Time-Resolved Fluorescence Immunoassay of Serum Alpha Fetoprotein-L3 Variant via LCA Magnetic Cationic Polymeric Liposomes Improves the Diagnostic Accuracy of Liver Cancer

Lei Wang,1,* Yiyi Liang,2,* Pengping Li,3 Qingchun Liang,4 Haijun Sun,5 Dazhou Xu,6 Wei Hu7
1Department of Oncology, Lianyungang Clinical College of Nanjing Medical University, The First People’s Hospital of Lianyungang, Lianyungang 222000, Jiangsu, People’s Republic of China; 2Department of Oncology, State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai Cancer Institute, Shanghai 200127, People’s Republic of China; 3Department of Bioinformatics, School of Basic Medical Sciences, Nanjing Medical University, Nanjing 210029, Jiangsu, People’s Republic of China; 4Department of Pathology, Second Xiangya Hospital, Central South University, Changsha, Hunan 410000, People’s Republic of China; 5Department of Thoracic Surgery, Lianyungang Clinical College of Nanjing Medical University, The First People’s Hospital of Lianyungang, Lianyungang 222000, Jiangsu, People’s Republic of China; 6Department of Gastroenterology, Lianyungang Clinical College of Nanjing Medical University, The First People’s Hospital of Lianyungang, Lianyungang 222000, Jiangsu, People’s Republic of China; 7Department of Hepatobiliary Surgery, Lianyungang Clinical College of Nanjing Medical University, The First People’s Hospital of Lianyungang, Lianyungang 222000, Jiangsu, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Wei Hu
Department of Hepatobiliary Surgery, Lianyungang Clinical College of Nanjing Medical University, The First People’s Hospital of Lianyungang, Lianyungang 222000, Jiangsu, People’s Republic of China
Tel +86-15950716158
Email doctorhu2019@163.com
Purpose: Ubiquitin-conjugating enzyme E2S (UBE2S) is important for the development and progression of several types of cancer. However, neither the role of UBE2S in pancreatic cancer nor its mechanism is clear. Methods: We analyzed three GEO datasets to obtain 150 differentially expressed genes (DEGs) between pancreatic ductal adenocarcinoma (PDAC) and non-cancerous samples. Moreover, GSEA and mutation analysis were also done for UBE2S. The UBE2S expression in PDAC was measured by immunohistochemistry and qRT-PCR. Colony formation, scratch wound-healing and tumor growth assays were conducted to examine the effect of UBE2S on PDAC cells. Migration was detected using Transwell assay. UBE2S knockdown pancreatic cells were treated with proteasome inhibitor MG132. Immunofluorescence was undertaken for interaction between UBE2S and VHL. The expression of Snail and Twist1 and the changes of HIF-1α/STAT3 pathway were detected by Western blotting. Results: The mRNA of UBE2S was significantly upregulated in human pancreatic cancer compared to normal tissues. Immunohistochemistry confirmed that the protein level of UBE2S increased in tissue microarrays (TMAs) and was associated with lymph nodes metastasis and distant metastasis. Conclusion: UBE2S could enhance EMT by the VHL/HIF-1α/STAT3 pathway via the ubiquitin-proteasome system. Co-expression of CDC20 may represent a novel and promising therapeutic target for the patients with PDAC. Keywords: pancreatic cancer, UBE2S, VHL/HIF-1α/STAT3 signaling, the ubiquitin-proteasome system, EMT
This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License . By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms .

Oncogenic Activities Of UBE2S Mediated By VHL/HIF-1&alpha;/STAT3 Signal Via The Ubiquitin-Proteasome System In PDAC

CARsgen Therapeutics (HKSE: 2171) operates as a biopharmaceutical company focused on CAR T-cell therapies for the treatment of hematologic malignancies and solid tumors. It offers an integrated cell therapy platform with in-house capabilities that span target discovery, antibody development, clinical trials, and commercial-scale manufacturing. The company was founded in 2014 and is based in Shanghai, China.

CARsgen Therapeutics

In September 2015 , CARsgen and Shanghai Cancer Institute entered into a five year research and development agreement for the advancement of CARsgen 's CAR-T cancer immunotherapeutics .

CARsgen Enters into Partnership Agreement with Shanghai Cancer Institute to Develop Novel CAR-T Technology.
-- Interim Phase 1 Study Results Encouraging, with Six Patients Suffering from Advanced Liver Cancer Successfully Treated --.

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