Page 217 - EJMO-9-2
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Eurasian Journal of
            Medicine and Oncology                                             Tetramethyl thyroxine boosts bladder cancer



            serum T4 and T3 levels and decreased TSH levels,   Science Foundation of China (92359202), National Key
            exhibiting a hyperthyroidism-like hormonal state,   Research and Development Program (2024YFC3405500),
            which may affect multiple organ systems and indirectly   “Open Competition to Select the Best Candidates”
            participate in regulating the tumor microenvironment.   Key Technology Program for Nucleic Acid Drugs of
            For example, by altering immune cell activity, vascular   NCTIB  (NCTIB2022HS01016),  and  the  Joint  Project of
            permeability, oxidative stress status, etc., all of which may   Biomedical Translational Engineering Research Center of
            promote the tumor development process. A systematic   Beijing University of Chemical Technology-China-Japan
            review and meta-analysis indicated an increased risk   Friendship Hospital (XK2023-21).
            of breast cancer in hyperthyroidism patients.  In these
                                                  48
            patients, THCA exhibited more aggressive behavior,   Conflict of interest
            with higher rates of local invasion and poor prognosis. 49  The authors declare that no commercial or financial

              In summary, our study has revealed the tumor-    conflicts of interest were identified in this research.
            promoting role of T4 in BC. However, we also acknowledge
            that T4 does not exhibit a tumor-promoting effect across all   Author contributions
            tumor types, especially when compared with T3, as there   Conceptualization: Zhao Yang
            are fundamental differences in their mechanisms of action   Data curation: Wenjing Zhang, Rui Guo
            and receptor dependency. Future research should further   Formal analysis: Wenjing Zhang
            explore the functional similarities and differences between   Investigation: Wenjing Zhang
            T4 and T3 in various cancer types; clarify their receptor-  Methodology: Wenjing Zhang
            mediated mechanisms; and investigate the correlation   Resources: Wenjing Zhang, Zhao Yang
            between thyroid function status and the occurrence,   Software: Wenjing Zhang
            progression, and prognosis of BC in clinical cohorts, to   Validation: Wenjing Zhang
            provide explanations with greater physiological relevance   Visualization: Wenjing Zhang
            and translational value.                           Writing–original draft: Wenjing Zhang, Zhao Yang
            5. Conclusion                                      Writing–editing & review: All authors

            In summary, our initial  in vitro experiments revealed   Ethics approval and consent to participate
            that T4 can promote the proliferation and migration of   The ethical approval has been obtained from the ethical
            BC cells while inhibiting their apoptosis. Subsequent   committee member board of the Animal Care Review
            in vivo experiments confirmed that increased serum   Committee of the China-Japan Friendship Hospital and
            concentrations of T4 in mice also promote the formation of   conducted in accordance with its recommendations
            BC tumor. Further mechanistic analysis indicated that T4   and ethical regulations. All experimental protocols
            facilitates the progression of BC by binding to the integrin   were approved by the ethical committee member board
            receptor  αV, which in turn influences the expression of   of  the  Animal  Care  Review  Committee of  the  China-
            VEGF and TP53 (Figure 6).                          Japan Friendship Hospital. The mice were maintained
              For the 1  time, we have demonstrated through both   under standard conditions according to the institutional
                      st
            in vivo and in vitro experiments that T4 can enhance the   guidelines for animal care (Ethics code: 2021-42-K26).
            development of BC and elucidate its molecular mechanism,
            thereby laying the groundwork for improved prevention,   Consent for publication
            diagnosis,  treatment,  and  prognosis  assessment of  this   Not applicable.
            disease.
                                                               Availability of data
            Acknowledgments
                                                               The data that support the findings of the study are available
            We are most grateful to Junying Jia (Institute of Biophysics,   from the corresponding author by e-mail upon reasonable
            Chinese Academy of Sciences) for his technical support in   request.
            flow cytometry.
                                                               References
            Funding
                                                               1.   Bray F, Laversanne M, Sung H, et al. Global cancer statistics
            Funding was received for the research, authorship, and/  2022: GLOBOCAN estimates of incidence and mortality
            or publication of this article. This work was supported   worldwide for 36 cancers in 185 countries. CA Cancer J Clin.
            by the Major Research Plan of the National Natural    2024;74(3):229-263.


            Volume 9 Issue 2 (2025)                        209                         doi: 10.36922/EJMO025080037
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