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Junhao Zhu Department of Neurosurgery, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu Province, China

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Chao Tang Department of Neurosurgery, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu Province, China

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Zixiang Cong Department of Neurosurgery, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu Province, China

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Feng Yuan Department of Neurosurgery, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu Province, China

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Xiangming Cai School of Medicine, Southeast University, Nanjing, Jiangsu Province, China

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Jin Yang Department of Neurosurgery, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu Province, China

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Chiyuan Ma Department of Neurosurgery, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu Province, China
School of Medicine, Southeast University, Nanjing, Jiangsu Province, China

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Dopamine agonist (DA) is the first choice for the treatment of prolactinomas, and drug resistance is unavoidable during treatment due to the heterogeneity of tumors. The two prolactinoma cell lines (GH3 cells and MMQ cells) were found to have different sensitivity and responding modes to the cabergoline (CAB) and bromocriptine (BRC). In this research, we disclosed the capability of ACT001, a derivative of parthenolide analogs, to activate AMPK by increasing the intracellular reactive oxygen species (ROS) level and AMP/ATP ratio to reverse DA resistance through dual pathways in prolactinoma cells. The results indicated that ACT001 could reverse the CAB resistance in GH3 cells by inhibiting the mTOR signaling pathway, inducing cell death through autophagy, and reverse the BRC resistance in MMQ cells by activating the EGR1 signaling pathway, inducing cell death through apoptosis. Our results suggested that ACT001 is a promising therapeutic compound for treating DA-resistant prolactinomas.

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Dingwen Liu Department of Urology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China

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Liang Zhou Department of Urology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China

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Cheng Li Department of Urology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China

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Youyou Li Department of Urology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China

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Jiahao Liu Department of Urology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China

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Lei Zhou Department of Urology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China

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Jin Tang Department of Urology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China

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Wei Xiong Department of Urology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China

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Long Wang Department of Urology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China

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This study provides a comprehensive analysis of global, continental, and national trends in the prevalence and mortality of prostate cancer (PC), breast cancer (BC), and thyroid cancer (TC). Utilizing 2021 Global Burden of Diseases (GBD2021) data, prevalence and death rates for 2021 were examined, with temporal trends from 1990 to 2021 analyzed via Joinpoint regression. Annual percentage change (APC) and average APC (AAPC) were calculated with 95% CI. Distributive inequalities were quantified using the slope index of inequality and concentration index. In 2021, PC, BC, and TC showed higher global age-standardized prevalence rates (ASPR) in Europe and America compared to Africa and Asia, while higher age-standardized death rates (ASDR) for PC and BC were noted in Africa. Over the study period, significant global increases in ASPR were observed for PC (AAPC = 0.78, 95% CI: 0.67 to 0.89), BC (AAPC = 0.31, 95% CI: 0.24 to 0.37), and TC (AAPC = 1.42, 95% CI: 1.31 to 1.52). Conversely, ASDR significantly decreased for PC (AAPC = −0.83, 95% CI: −0.92 to −0.74), BC (AAPC = −0.48, 95% CI: −0.56 to −0.39), and TC (AAPC = −0.23, 95% CI: −0.29 to −0.17). Variations were observed across continents and time periods, affecting 204 countries and territories. Higher Social Development Index (SDI) levels were associated with a more pronounced burden of these cancers. The findings highlight significant global heterogeneity in prevalence, death rates, and temporal trends of endocrine cancers, with important implications for epidemiology and public health policies.

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Fei Han Institute of Toxicology, College of Preventive Medicine, Army Medical University, Chongqing, China

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Wen-bin Liu Institute of Toxicology, College of Preventive Medicine, Army Medical University, Chongqing, China

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Jian-jun Li Department of Oncology, Southwest Hospital, Army Medical University, Chongqing, China

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Ming-qian Zhang Department of Emergency, Yan’an Hospital, Kunming Medical University, Kunming, Yunnan Province, China

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Jun-tang Yang Institute of Toxicology, College of Preventive Medicine, Army Medical University, Chongqing, China

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Xi Zhang Institute of Toxicology, College of Preventive Medicine, Army Medical University, Chongqing, China

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Xiang-lin Hao Institute of Toxicology, College of Preventive Medicine, Army Medical University, Chongqing, China

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Li Yin Institute of Toxicology, College of Preventive Medicine, Army Medical University, Chongqing, China

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Cheng-yi Mao Department of Pathology, Daping Hospital, Army Medical University, Chongqing, China

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Xiao Jiang Institute of Toxicology, College of Preventive Medicine, Army Medical University, Chongqing, China

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Jia Cao Institute of Toxicology, College of Preventive Medicine, Army Medical University, Chongqing, China

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Jin-yi Liu Institute of Toxicology, College of Preventive Medicine, Army Medical University, Chongqing, China

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New potential biomarkers and therapeutic targets for ovarian cancer should be identified. The amplification in chromosomal region 5q31–5q35.3 exhibits the strongest correlation with overall survival (OS) of ovarian cancer. SOX30 coincidentally located at this chromosomal region has been determined as a new important tumor suppressor. However, the prognostic value, role and mechanism of SOX30 in ovarian cancer are unexplored. Here, we reveal that SOX30 is frequently overexpressed in ovarian cancer tissues and is associated with clinical stage and metastasis of ovarian cancer patients. High SOX30 expression predicts better OS and acts as an independent prognostic factor in advanced-stage patients, but is not associated with OS in early-stage patients. Based on the survival analyses, the advanced-stage patients with high SOX30 expression can receive platin- and/or taxol-based chemotherapy, whereas they should not receive chemotherapy containing gemcitabine or topotecan. Functionally, SOX30 strongly inhibits tumor cell migration and invasion in intro and suppresses tumor metastasis in vivo. SOX30 regulates some markers (E-CADHERIN, FIBRONECTIN, N-CADHERIN and VIMENTIN) and prevents the characteristics of epithelial–mesenchymal transition (EMT). SOX30 transcriptionally regulates the expression of E-CADHERIN, FIBRONECTIN and N-CADHERIN by binding to their promoters. Restoration of E-CADHERIN and/or N-CADHERIN when overexpressing SOX30 significantly reduces the anti-metastatic role of SOX30. Indeed, chemotherapy treatment containing platin or gemcitabine combined with SOX30 expression influences tumor cell metastasis and the survival of nude mice differently, which is closely associated with EMT. In conclusion, SOX30 antagonizes tumor metastasis by preventing EMT process that can be used to predict survival and incorporated into chemotherapeutics of advanced-stage ovarian cancer patients.

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Fei Han Institute of Toxicology, College of Preventive Medicine

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Wen-bin Liu Institute of Toxicology, College of Preventive Medicine

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Jian-jun Li Department of Oncology, Southwest Hospital, Army Medical University, Chongqing, China

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Ming-qian Zhang Department of Emergency, Yan’an Hospital, Kunming Medical University, Kunming, Yunnan Province, China

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Jun-tang Yang Institute of Toxicology, College of Preventive Medicine

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Xi Zhang Institute of Toxicology, College of Preventive Medicine

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Xiang-lin Hao Institute of Toxicology, College of Preventive Medicine

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Li Yin Institute of Toxicology, College of Preventive Medicine

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Cheng-yi Mao Department of Pathology, Daping Hospital, Army Medical University, Chongqing, China

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Xiao Jiang Institute of Toxicology, College of Preventive Medicine

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Jia Cao Institute of Toxicology, College of Preventive Medicine

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Jin-yi Liu Institute of Toxicology, College of Preventive Medicine

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