Thyroid最新文献

{"title":"MarginView3D: Extending Novel 3D Surgical Pathology Reporting for Use in Invasive pT4 Thyroid Cancer and Other Surgical Oncologic Procedures.","authors":"Sabrina R Comess, Jacob E Kapustin, Margaret Nurimba, Ike Kwon, Margaret Brandwein-Weber, Michael Karasick, Mark L Urken","doi":"10.1177/10507256261431842","DOIUrl":"10.1177/10507256261431842","url":null,"abstract":"<p><strong>Background: </strong>The American Thyroid Association's most recent clinical practice guidelines include margin status as a key factor to estimate risk of recurrence. Unlike most thyroid cancers, the successful resection of invasive pT4 thyroid cancers necessitates the use of frozen section analysis (FSA). There is no standardized method for intraoperative surgical margin assessment. We developed a novel intraoperative workflow and software platform, MarginView3D^TM (MV3D), to enhance the precision of FSA and improve surgical pathology reporting in head and neck cancer. Here, we demonstrate its use in invasive thyroid cancer.</p><p><strong>Methods: </strong>We describe the MV3D^TM surgical pathology reporting software and detail our surgical workflow, which incorporates 3D scanning technology and standardized \"timeouts\" to facilitate intraoperative communication and pathologic documentation. This approach was utilized in five invasive pT4 thyroid cancer cases.</p><p><strong>Results: </strong>MV3D^TM was used to guide intraoperative margin assessment, communication, and pathologic documentation in four tracheal resections and one sternal mass resection. A final surgical pathology report was generated for each case, integrating 3D scans, annotated radiographs, and audiovisual summaries into a dynamic interface for multidisciplinary use. We highlight case 5, where MV3D^TM facilitated bidirectional communication between the surgeon and pathologist to guide precise harvesting of supplemental margins. The surgeon and pathologist collaborated in real time to address at-risk areas requiring immediate re-resection. An R0 resection was achieved, and all relevant details were captured within MV3D^TM.</p><p><strong>Conclusions: </strong>We have utilized our novel approach extensively in head and neck cancer. Here, we highlight it as a tool for the management of invasive pT4 thyroid cancer. As a brief summary of new and innovative research, this study introduces MV3D^TM as a novel and scalable approach to intraoperative margin assessment and documentation in advanced thyroid cancer, with the potential to inform future practice in surgical oncology.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"467-470"},"PeriodicalIF":6.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147390861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patient-Reported Outcomes Three Years After Deciding on Surgery or Active Surveillance for Small, Low-Risk Papillary Thyroid Cancer: Results of a Prospective Cohort Study.","authors":"Anna M Sawka, Sangeet Ghai, Lorne Rotstein, Jonathan C Irish, Jesse D Pasternak, Katherine Lajkosz, Wei Xu, Jennifer M Jones, Amiram Gafni, Nancy N Baxter, David P Goldstein","doi":"10.1177/10507256251408857","DOIUrl":"10.1177/10507256251408857","url":null,"abstract":"<p><strong>Background: </strong>Long-term quality of life is an important consideration of patients in deciding on disease management options for low-risk papillary thyroid cancer (PTC).</p><p><strong>Methods: </strong>We conducted a prospective cohort study of Canadian patients who were diagnosed with small (<2 cm in maximal diameter), low-risk papillary thyroid cancer (PTC) and were given the choice of active surveillance (AS) or immediate surgery. We report the results of a self-administered questionnaire on patient-reported outcomes (PROs) that was completed approximately three years after the initial disease management choice. PROs included overall and subscale scores from questionnaires, including those on quality of life (EORTC QLQ-C30, EORTC THY-34), the Assessment of Survivor Concerns, the Decision Regret Scale, and the Generalized Anxiety Disorder 7-item Scale. We compared the results according to the initial disease management choice and according to the disease management status at the time of questionnaire completion.</p><p><strong>Results: </strong>The participant response rate was 64% (120/188), including 98 individuals who chose AS and 22 who chose immediate surgery. The median duration of follow-up at the time of questionnaire completion was 42 months (interquartile range [IQR] = 39, 46). After statistical adjustment for multiple comparisons, there were no significant differences in the overall scores or subscales of any of the questionnaires between patients who chose AS and those who chose immediate surgery. However, in a secondary analysis, patients who crossed over from AS to surgery experienced greater cancer-related worry as well as overall worry (<i>p</i> = 0.021 for each) and decision regret (<i>p</i> = 0.031) as compared with patients who remained under AS and those who initially chose surgery.</p><p><strong>Conclusions: </strong>We observed that PROs do not significantly differ between patients who chose AS and those who chose immediate surgery a few years after the initial disease management choice. However, patients who crossover from AS to surgery may experience greater cancer-related worry and decision regret.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"385-396"},"PeriodicalIF":6.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147435641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Effect of Standardized Postoperative Neck and Orofacial Rehabilitation Exercise on Quality of Life in Post-Thyroidectomy Patients: A Randomized Controlled Trial.","authors":"Jiayong Huang, Wanna Chen, Jing Zhang, Heyang Xu, Yongxue Li, Yihao Liu, Bo Lin, Ruixia Li, Mingwei Liang, Xiangdong Xu, Weiming Lv","doi":"10.1177/10507256261427761","DOIUrl":"10.1177/10507256261427761","url":null,"abstract":"<p><strong>Background: </strong>Approximately 80% of post-thyroidectomy patients suffer from swallowing disorders even in the absence of definite laryngeal nerve injury. This study aimed to evaluate the efficacy of a standardized postoperative neck and orofacial rehabilitation exercise in enhancing quality of life (QoL), particular swallowing-related QoL, among post-thyroidectomy patients without definite laryngeal nerve injury during surgery.</p><p><strong>Methods: </strong>This was a single-center, open-label randomized controlled trial. The trial was registered at the Chinese Clinical Trial Registry (ChiCTR2500097960). Participants were randomized 1:1 to rehabilitation exercise group (RE group) and control group. The RE group performed a standardized postoperative neck and orofacial rehabilitation exercise, which included neck extension, swallowing, and voice training, while the control group received only general advice to move their necks freely. The rehabilitation exercise program duration is 3 months. The QoL of participants was evaluated at 1 week, 1 month, 3 months, and 6 months postoperatively. The primary outcome was swallowing-related QoL evaluated by the MD Anderson Dysphagia Inventory (MDADI) at 1 month after surgery. Secondary outcomes included swallowing-related QoL at other follow-up time points, the thyroid cancer-specific QoL, scar assessment, and safety endpoints defined by postoperative drainage, pain scores, and adverse events.</p><p><strong>Results: </strong>A total of 374 patients were recruited, and 356 participants were included in final analysis, including 176 in RE group and 180 in control group. The swallowing-related QoL in the RE group was significantly better than that in the control group at 1 month (MDADI total score 97.4 [80.3, 100] vs. 88.9 [75.8, 99.7], <i>p</i> = 0.004) and 6 months (MDADI total score 100 [96.8, 100] vs. 98.9 [85.5, 100], <i>p</i> = 0.020) postoperatively. The RE group reported higher pain levels at 1 week after surgery (<i>p</i> = 0.013) but no significant differences at subsequent time points. No statistically significant differences between groups were observed in other outcomes. No severe adverse event occurred during rehabilitation exercise.</p><p><strong>Conclusions: </strong>The standardized postoperative neck and orofacial rehabilitation exercise was an effective and safe approach for accelerating the recovery of the swallowing-related QoL in post-thyroidectomy patients without definite laryngeal nerve injury during surgery.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"397-407"},"PeriodicalIF":6.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147356446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel Deiodinase 2-Selective Inhibitors-Possible Reference Substances for Regulatory <i>In Vitro</i> Tests for Endocrine Disruptors and Drugs Targeting T3-Dependent Processes.","authors":"Caroline Frädrich, Niklas Wiese, Yiming Zhang, Rajas Sane, Anja Fischbach, Eva K Wirth, Martin Neuenschwander, Jens Peter von Kries, Carola Seyffarth, Sabrina Kleissle, Kostja Renko, Josef Köhrle","doi":"10.1177/10507256261425689","DOIUrl":"10.1177/10507256261425689","url":null,"abstract":"<p><strong>Background: </strong>Thyroid hormone (TH) homeostasis depends on the coordination of several key events to maintain proper local TH signaling, including iodide uptake, hormone synthesis, metabolism, and elimination. Three selenoprotein isoenzymes, deiodinases 1-3 (DIO1-3), are essential components of TH metabolism, and their activities have been identified as relevant endpoints regarding the screening of compounds influencing the TH system. Given the importance of DIO2 as the key enzyme for local activation of the prohormone T4 to the active T3 in various tissues, and limited data on selective biochemical DIO2 inhibition, there is a clear need to identify potent and selective DIO2-inhibiting compounds.</p><p><strong>Methods: </strong>Human-recombinant DIO2 enzyme pools were prepared from HEK293 cells overexpressing DIO2 and used as a robust enzyme source for the development, optimization, and semiautomated miniaturization of a nonradioactive DIO2 high-throughput screening (HTS) enzyme assay for the identification of DIO2-selective small molecule inhibitors. LT4 was used as substrate, and enzymatic release of iodide was colorimetrically quantified by the iodide-catalyzed Sandell-Kolthoff reaction. Eight comprehensive small molecule libraries were screened, covering ∼1/5 of the synthetic chemicals currently registered, natural products, as well as FDA-approved drugs. A total of 59,928 compounds were first screened at a single 10 µM concentration, followed by a validation screen to confirm the primary hits. Subsequently, DIO isoenzyme selectivity and cytotoxicity were evaluated.</p><p><strong>Results: </strong>Utilizing this highly reproducible and robust HTS test system with a determined median Z'-factor of 0.70 identified 356 primary inhibitory hits. Concentration-response experiments verified 17 potent inhibitors, further characterized regarding their DIO isoenzyme selectivity and cytotoxicity. Six potent DIO2-selective inhibitors, including two FDA-approved drugs and various novel pan-DIO inhibitors, for example, the fungicide fluazinam, were identified.</p><p><strong>Conclusions: </strong>Specific DIO2 inhibitors, such as the FDA-approved drugs racecadotril and ibrutinib and the tyrosine kinase inhibitor rociletinib, might serve as a future toolbox for reversible pharmacological interference with the local provision of DIO2-generated T3 from T4 during development, tissue regeneration, and various DIO2-dependent metabolic processes. Furthermore, they can serve as reference compounds for the development and validation of regulatory <i>in vitro</i> tests. Identified FDA-approved drugs warrant a closer look at potential disturbances of local TH availability.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"451-462"},"PeriodicalIF":6.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147445208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnostic Performance of Five Societies' Ultrasound Risk Stratification Systems for Thyroid Malignancy According to Nodule Size: A Comparison Using a Standardized Ultrasound Lexicon.","authors":"Dong Gyu Na, Byeong-Joo Noh, Won Jun Kim, Jin Yub Kim, Ha Young Kim, Jong Cheol Lee, Myoung Sook Shim, Yong Jin Song, Kwang Hyun Yoon, Wooyul Paik","doi":"10.1177/10507256261429117","DOIUrl":"10.1177/10507256261429117","url":null,"abstract":"<p><strong>Background: </strong>Accurate understanding of the reasons for the differing performance of current ultrasound (US) risk stratification systems (RSSs) is essential for developing a unified RSS. We aimed to compare the diagnostic performance of five RSSs according to nodule size, using standardized US lexicon proposed by international expert consensus.</p><p><strong>Methods: </strong>From March 2017 to February 2024, 3774 thyroid nodules (>1 cm) with final diagnoses (3053 benign and 721 malignant) were retrospectively analyzed. The US features of nodules were assessed during real-time examinations, and the nodules were retrospectively classified according to the US criteria of each RSS using standardized lexicon. We compared the distribution, malignancy risk, and inter-system agreement of nodule categories, along with the distribution of malignant tumors across these categories, among the American Thyroid Association (ATA) system and the European (EU-), Korean (K-), American College of Radiology (ACR-), and Chinese (C-) Thyroid Imaging Reporting and Data Systems (TIRADSs). Diagnostic performance based on biopsy criteria was compared among the five RSSs according to nodule size (small ≤ 2 cm and large > 2 cm).</p><p><strong>Results: </strong>Significant differences were observed in the distribution of classified nodules, malignant tumor distribution across categories, and malignancy risk of most categories (all <i>p</i> < 0.001), with widely varying inter-system agreement (κ = 0.05-0.85). The ATA system and EU-TIRADS demonstrated higher sensitivity and unnecessary biopsy rate (UBR) in both small and large nodule groups, whereas ACR TI-RADS showed lower sensitivity and UBR across both sizes. K-TIRADS exhibited the lowest sensitivity and UBR for small nodules (all <i>p</i> < 0.001) but showed high sensitivity and UBR for large nodules. C-TIRADS showed a similarly low sensitivity but exhibited a higher UBR (all <i>p</i> < 0.001) in both size groups compared with ACR TI-RADS.</p><p><strong>Conclusions: </strong>The five RSSs differed considerably in nodule classification, malignancy risk across categories, and diagnostic performance according to nodule size. The differences in diagnostic performance stem primarily from variations in biopsy size thresholds and US criteria for small nodules, and disparate US criteria for no-biopsy-indicated large nodules. Optimizing risk stratification and biopsy thresholds, particularly for large nodules, is required for establishing a unified TIRADS.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"408-419"},"PeriodicalIF":6.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147365933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Patterns and Risk Factors for Antidepressant Drug Prescription in Thyroid Cancer Patients and Survivors: Analysis Based on the Korean National Health Insurance Service Database.","authors":"Yea Eun Kang, Chul-Hyun Cho, Minchul Song, Ju Hee Lee, Eun Kyung Lee, Young Joo Park, Shinje Moon, Bon Seok Koo","doi":"10.1177/10507256261431793","DOIUrl":"10.1177/10507256261431793","url":null,"abstract":"<p><strong>Background: </strong>Thyroid cancer is the most common endocrine malignancy and typically carries an excellent prognosis, especially in differentiated thyroid cancer (DTC). However, many survivors experience psychological challenges, including depression, which can significantly affect their long-term quality of life. While thyroid cancer treatment often involves surgery and hormone therapy, the relationship between treatment-related variables and new-onset depression remains poorly understood. Identifying clinical and treatment-related factors associated with depression is critical for improving postoperative survivorship care.</p><p><strong>Methods: </strong>We conducted a retrospective cohort study using data from the National Health Insurance Service-National Health Screening Cohort, which includes approximately 10% of the South Korean population aged 40-79 years. We included patients diagnosed with thyroid cancer (International Classification of Diseases version 10 [ICD-10] code C73) between 2002 and 2019 and excluded those with a prior diagnosis of depression or other cancers. Variables analyzed included treatment modality (active surveillance, lobectomy, total thyroidectomy [TT]), age, sex, income, smoking, alcohol consumption, physical activity, body mass index, blood pressure, presence of hypertension or diabetes, radioactive iodine (RAI) dose, and thyroid hormone replacement. The primary outcome was newly diagnosed depression, defined by a new prescription of antidepressants and corresponding diagnostic codes.</p><p><strong>Results: </strong>Among 6968 thyroid cancer patients included in the analysis, the risk of new-onset depression was significantly elevated in patients who underwent no treatment (hazard ratio [HR]: 1.33; 95% confidence interval [CI]: 1.06-1.66), lobectomy (HR: 1.30; 95% CI: 1.11-1.52), or TT (HR: 1.20; 95% CI: 1.09-1.32) compared with matched controls without thyroid cancer (all <i>p</i> < 0.05). There was no significant association between depression risk and cumulative RAI dose or levothyroxine dosage. Antidepressant prescription incidence was significantly higher within the first five years postdiagnosis but not beyond five years.</p><p><strong>Conclusions: </strong>Thyroid cancer diagnosis and treatment are associated with an increased risk of prescription of antidepressants in Korea.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"431-440"},"PeriodicalIF":6.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147469263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronic Iodine Excess and Aging Synergistically Impact Thyrotropin Elevation: A Prospective 20-Year Follow-Up Study in China.","authors":"Xiaotong Gao, Weiping Li, Qingling Gu, Yushu Li, Yongze Li, Haoyu Wang, Xiaochun Teng, Di Teng, Shuangning Ding, Weiping Teng, Zhongyan Shan","doi":"10.1177/10507256261427353","DOIUrl":"10.1177/10507256261427353","url":null,"abstract":"<p><strong>Background: </strong>Chronic iodine excess is associated with increased serum thyrotropin (TSH) levels. We assessed the independent and interactive effects of iodine-excess transition outcomes and aging on TSH levels over 20-year follow-up.</p><p><strong>Methods: </strong>The original prospective cohort study started in 1999 and focused on three communities in North China (<i>n</i> = 1176). Based on the iodine status transition over the 20-year period, the euthyroid participants were categorized into groups according to urinary iodine concentrations (UIC): continuous iodine sufficiency (UIC 100-299 μg/L) (SI-SI, <i>n</i> = 261), from iodine excess (UIC >299 μg/L) to iodine deficiency (UIC <100 μg/L) (EI-DI, <i>n</i> = 145), from iodine excess to iodine sufficiency (EI-SI, <i>n</i> = 530), and continuous iodine excess (EI-EI, <i>n</i> = 240), respectively.</p><p><strong>Results: </strong>During 1999-2004, the baseline median TSH levels were positively associated with the initial UIC levels. After 20 years, for participants with negative thyroid antibodies, the three iodine-excess groups all exhibited elevated median TSH levels (SI-SI 1.81 mU/L vs. EI-DI 2.19 mU/L vs. EI-SI 2.08 mU/L vs. EI-EI 2.01 mU/L), an increased prevalence of mild subclinical hypothyroidism (SCH) with TSH <10.0 mU/L (SI-SI 5.3% vs. EI-DI 11.2% vs. EI-SI 12.3% vs. EI-EI 9.4%) and reduced central thyroid hormone sensitivity compared with the SI-SI group (<i>p</i> < 0.05). However, the EI-EI group had the lowest TSH rising degree (SI-SI 0.32 mU/L [24.57%] vs. EI-DI 0.47 mU/L [24.56%] vs. EI-SI 0.45 mU/L [37.52%] vs. EI-EI 0.21 mU/L [14.18%], <i>p</i> < 0.05). Repeated-measures analysis revealed that aging was primarily related to a stable increase in TSH. Iodine-excess transition outcomes were also associated. Furthermore, a significant interaction effect existed between aging and different iodine-excess transition outcomes, modulating the TSH rising degree. Alleviation of iodine excess promoted aging-related TSH elevation, whereas persistent iodine excess suppressed aging-related TSH elevation. However, among participants with positive thyroid antibodies, no significant interaction effect above was observed. By comparison, there was a greater prevalence of SCH, especially an obvious high prevalence of severe SCH under persistent iodine excess.</p><p><strong>Conclusions: </strong>Elevated TSH levels induced by chronic iodine excess cannot be downregulated by reducing iodine intake. In nonautoimmune contexts, an interaction effect between iodine status and aging synergistically modulates the TSH rising degree. Iodine excess contributes to mild SCH and is correlated with high baseline TSH levels.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"420-430"},"PeriodicalIF":6.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147390940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Radioactive Iodine and Female Fertility: Are We Underestimating the Risk?","authors":"Panagiotis Anagnostis, Julia K Bosdou","doi":"10.1177/10507256261430251","DOIUrl":"10.1177/10507256261430251","url":null,"abstract":"","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"10507256261430251"},"PeriodicalIF":6.7,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147390758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patient-Derived <i>in Vitro</i> Models Reveal Insights into Medullary Thyroid Cancer Microenvironment and Resistance to Tyrosine Kinase Inhibitors.","authors":"Elisa Stellaria Grassi, Viola Ghiandai, Germano Gaudenzi, Elena Massardi, Valentina Cirello, Erika Carbone, Davide Gentilini, Sarah Uraghi, Giacomo Gazzano, Gianlorenzo Dionigi, Carla Colombo, Giovanni Vitale, Laura Fugazzola, Luca Persani","doi":"10.1177/10507256251408825","DOIUrl":"10.1177/10507256251408825","url":null,"abstract":"<p><strong>Background: </strong>Medullary thyroid carcinoma (MTC) is a rare neuroendocrine malignancy with a 10-year mortality rate up to 50%. Current therapies for metastatic MTC comprise various tyrosine-kinase inhibitors, but resistance often appears due to the need for lifelong treatments. Like in other tumors, genetic, epigenetic, post-transcriptional, post-translational, and cell-cell interaction events influence drug response. However, progress in understanding MTC biology is limited by the lack of reliable <i>in vivo</i> and <i>in vitro</i> models. This study aims to develop a patient-derived model faithfully reproducing the microenvironmental alterations present in MTC.</p><p><strong>Methods: </strong>We applied a two-step protocol consisting of a first phase in which primary cells are cultivated as multicellular spheroids and a second phase in which they are switched to adherent cultures. After evaluation of the genetic background by targeted Next Generation Sequencing, we characterized our cells phenotype by examining a panel of stem/progenitor-related markers, the secretory abilities by ELISAs, the drug response by proliferation assays, the <i>in vivo</i> angiogenic and invasiveness by the use of zebrafish model, the <i>in vitro</i> invasivity by Matrigel Dome assays and the spatial variation of stem/progenitor marker in both 3D cell models and tissue samples by confocal microscopy.</p><p><strong>Results: </strong>Our model allowed the establishment of eight MTC patient-derived cell lines with different genetic backgrounds. The cultures faithfully reproduced the changes in stem and progenitor markers that we detected in our cohort of MTC tissue samples and could be successfully xenotransplanted in zebrafish model, showing both angiogenetic and invasive properties. Drug screening assays revealed the potential of our model for the study of patient-specific responses, as we were able to identify different candidate regulators of the sensitivity to currently available therapies for MTC.</p><p><strong>Conclusions: </strong>Our two-step protocol successfully generated primary MTC lines that maintain high plasticity, can be cultivated for several passages, and recreate the heterogeneity observed in patients' tissues. Our model will offer a robust platform for preclinical drug testing and mechanistic studies, addressing a longstanding gap in MTC research. It enables exploration of tumor microenvironment interactions and personalized therapeutic responses, supporting progress beyond current genomic-driven frameworks.</p>","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"291-304"},"PeriodicalIF":6.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146126436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Celebration of International Women's Day: Bobbi Rath Smith's Leadership Contributions to the American Thyroid Association: Executive Director, CEO, 2001-2020.","authors":"Victor Bernet","doi":"10.1177/10507256261425601","DOIUrl":"10.1177/10507256261425601","url":null,"abstract":"","PeriodicalId":23016,"journal":{"name":"Thyroid","volume":" ","pages":"227-228"},"PeriodicalIF":6.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146182585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}