Random Forest for Predicting Treatment Response to Radioiodine and Thyrotropin Suppression Therapy in Patients With Differentiated Thyroid Cancer But Without Structural Disease.

BACKGROUND: We aimed to develop a machine-learning model for predicting treatment response to radioiodine (131I) therapy and thyrotropin (TSH) suppression therapy in patients with differentiated thyroid cancer (DTC) but without structural disease, based on pre-treatment information. PATIENTS AND METHODS: Overall, 597 and 326 patients with DTC but without structural disease were randomly assigned to "training" cohorts for predicting treatment response to 131I therapy and TSH suppression therapy, respectively. Six supervised algorithms, including Logistic Regression, Support Vector Machine, Random Forest (RF), Neural Networks, Adaptive Boosting, and Gradient Boost, were used to predict effective response (ER) to 131I therapy and biochemical remission (BR) to TSH suppression therapy. RESULTS: Stimulated and suppressed thyroglobulin (Tg) and radioiodine uptake before the current course of 131I therapy were mostly attributed to ER to 131I therapy, while thyroid remnant available on the post-therapeutic whole-body scan at the last course of 131I therapy and TSH were greatly contributed to Tg decline under TSH suppression therapy. RF showed the best performance among all models. The accuracy and area under the receiver operating characteristic curve (AUC) for segregating ER from non-ER during 131I therapy with RF were 81.3% and 0.896, respectively. The accuracy and AUC for predicting BR to TSH suppression therapy with RF were 78.7% and 0.857, respectively. CONCLUSION: This study demonstrates that machine learning models, especially the RF algorithm are useful tools that may predict treatment response to 131I therapy and TSH suppression therapy in DTC patients without structural disease based on pre-treatment routine clinical variables and biochemical markers.

[Efficacy of bronchoalveolar lavage combined with prone positioning in children with Mycoplasma pneumoniae pneumonia and atelectasis: a prospective randomized controlled study]. / æ”¯æ°”ç®¡è‚ºæ³¡çŒæ´—è”åˆä¿¯å§ä½æ²»ç–—å„¿ç«¥è‚ºç‚Žæ”¯åŽŸä½“è‚ºç‚Žä¼´è‚ºä¸å¼ ç–—æ•ˆçš„å‰çž»æ€§éšæœºå¯¹ç §ç ”ç©¶.

OBJECTIVES: To study the efficacy of bronchoalveolar lavage (BAL) combined with prone positioning in children with Mycoplasma pneumoniae pneumonia (MPP) and atelectasis and its effect on pulmonary function. METHODS: A prospective study was conducted on 94 children with MPP and atelectasis who were hospitalized in Ordos Central Hospital of Inner Mongolia from November 2020 to May 2023. The children were randomly divided into a treatment group and a control group, with 47 children in each group. The children in the treatment group were given conventional treatment, BAL, and prone positioning, and those in the control group were given conventional treatment and BAL. The two groups were compared in terms of fever, pulmonary signs, length of hospital stay, lung recruitment, and improvement in pulmonary function. RESULTS: Compared with the control group, the treatment group had significantly shorter time to improvement in pulmonary signs and length of hospital stay and a significantly higher rate of lung recruitment on day 7 of hospitalization, on the day of discharge, and at 1 week after discharge (P<0.05). Compared with the control group, the treatment group had significantly higher levels of forced vital capacity (FVC) as a percentage of the predicted value, forced expiratory volume (FEV) in 1 second as a percentage of the predicted value, ratio of FEV in 1 second to FVC, forced expiratory flow at 50% of FVC as a percentage of the predicted value, forced expiratory flow at 75% of FVC as a percentage of the predicted value, and maximal mid-expiratory flow as a percentage of the predicted value on the day of discharge and at 1 week after discharge (P<0.05). There was no significant difference in the time for body temperature to return to normal between the two groups (P>0.05). CONCLUSIONS: In the treatment of children with MPP and atelectasis, BAL combined with prone positioning can help to shorten the time to improvement in pulmonary signs and the length of hospital stay and promote lung recruitment and improvement in pulmonary function.

Second radioiodine treatment hardly benefits TT-DTC patients with radioiodine-negative metastases on initial post-therapeutic whole-body scans.

BACKGROUND: The effect of second 131I treatment (RT) in totally thyroidectomized differentiated thyroid cancer (TT-DTC) patients with true-positive thyroid beds and false-negative metastasis (TB+/M-) on initial post-therapeutic whole-body scan (Rx-WBS) remains unknown. METHODS: TT-DTC patients with TB+/M- on initial Rx-WBS receiving and not receiving second RT were categorized into group A and group B, respectively, while patients with 131I-avid metastasis receiving second RT were referred to as group C. Biochemical remission (BR) was defined as a decrease of ≥25.0% in thyrotropin-suppressed thyroglobulin (Tgon) level, while the structural response (SR) was determined by the change in the size of the largest lesion. RESULTS: In total, 145 patients were eligible. In group A, the median Tgon measured 3.3 ng/mL before and 3.0 ng/mL at 4 months after second RT (P=0.307), yielding a decrease in the median Tgon (∆Tgon%) of 13.3%, a BR rate of 36%, and an insignificant SR, which were comparable to those in group B. In group C, however, a median ∆Tgon% of 37.8% and a BR rate of 64% were obtained, which were significantly higher than those in group A (P=0.038 and 0.022, respectively), with SR distributions similar to those in group A. In addition, 131I uptake in the neck was not statistically associated with the detection of metastasis on initial Rx-WBS. CONCLUSIONS: This controlled study demonstrated a subtle response to second RT in TT-DTC patients with TB+/M- on initial Rx-WBS, representing a meaningful advancement in avoiding ineffective repeated RT.

[Series of group standards of Technical Specifications for Revision of Safety Information in Marketed Chinese Patent Medicine Instructions].

Drug instructions,the statutory and technical documents recording effectiveness and safety information,are an important basis for guiding doctors,pharmacists,and patients to use drugs rationally,and their scientificity,standardization,and accuracy directly affect the medication safety of the public. The sections of adverse drug events,contraindications,precautions,warnings,and application for specific populations in drug instructions directly express safety information and measures for rational use of drugs. In the drug life cycle,marketing authorization holders( MAHs) need to update safety information in the instructions promptly to ensure the safety and effectiveness of clinical drug medication. At present,revising instructions is an important measure to control drug risks. In the drug life cycle,in order to standardize the revision of safety information in the instructions by MAHs and eliminate inexact terms such as " unclear",the Technical Specifications for Revision of Safety Information in Marketed Chinese Patent Medicine Instructions,a series of group standards,have been established under the guidance of Standardization Department,China Association of Chinese Medicine. Therefore,on the basis of the existing rules and regulations,the standardized technical procedures for revising instructions came into being to help clinical safe and rational medication of drugs,and implement the strategy of " Healthy China".

[Interpretation of Technical Specifications for Revision of Safety Information in Marketed Chinese Patent Medicine Instructions].

Technical Specifications for Revision of Safety Information in Marketed Chinese Patent Medicine Instructions,a series of group standards,were proposed by Professor ZHANG Bing from Research Center for Pharmacovigilance and Rational Use of Traditional Chinese Medicine,and underwent centralized management by Chinese Association of Chinese Medicine. They were officially released on July 23 and implemented on July 31,2021. The series of group standards consist of six sections,including general principles,adverse drug events,contraindications,precautions,application for special populations,and warnings. The section of general principles is comprised of holistic and programmatic expressions,which explain the general technical requirements for revising the marketed Chinese patent medicine instructions. The other five sections focus on information collection,screening,transformation,and illustration of specific items,forming a standardized revision technical process. This series of standards is the result of multiple rounds of research and the suggestions of more than 200 experts in different professional fields of " medicine-pharmacy-management-law-enterprise" have been gathered therein to reach a consensus. With the purposes of establishing standardized technical specifications for the revision of safety information in the marketed Chinese patent medicine instructions,guiding marketing authorization holders in revising the instructions,filling the gaps in the research of Chinese patent medicine instructions,promoting the deve-lopment of pharmaceutical care and academic research,and encouraging the rational and safe medication of Chinese patent medicine,the series of group standards is of great significance.

Updated Review of Nuclear Molecular Imaging of Thyroid Cancers.

OBJECTIVES: We initiate this comprehensive review to update the advances in this field by objectively elucidating the efficacies of promising radiopharmaceuticals. METHODS: We performed a comprehensive PUBMED search using the combined terms of "thyroid cancer" and "radiopharmaceuticals" or "nuclear medicine", yielding 3273 and 11026 articles prior to December 31, 2020, respectively. RESULTS: Based on the mechanism of molecular metabolism, the evaluation of differentiated thyroid cancer and dedifferentiated thyroid cancer is largely centered around radioiodine and fluorine 18 (18F)-fludeoxyglucose, respectively. Further, 18F-L-dihydroxyphenylalanine and gallium 68 DOTATATE are the preferred tracers for medullary thyroid cancer. In dedifferentiated medullary thyroid cancer and anaplastic thyroid cancer, 18F-fludeoxyglucose is superior. CONCLUSIONS: The future lies in advances in molecular biology, novel radiopharmaceuticals and imaging devices, paving ways to the development of personalized medication for thyroid cancer patients.

[Technical specification for Instructions for Clinical Application of Chinese Patent Medicines in China Association of Chinese Medicine].

In order to solve the problems of confusion in clinical medication and imperfect instructions in Chinese patent medicines(CPMs), the Standardization Department of the China Association of Chinese Medicine and Center for Pharmacovigilance and Rational use of Chinese Medicine in Beijing University of Chinese Medicine jointly compiled the Instructions for Clinical Application of Chinese Patent Medicines(CPMs). As the interpretation and supplement of drug instruction information, it aims to guide clinical safety and rational use of CPMs. In addition, the technical specification for clinical application description of CPMs has been formulated, which covers the seven processes of "carding instructions, clinical investigation, data retrieval, data screening, evidence classification, path transformation and writing format". It will enable readers of Instructions for Clinical Application of Chinese Patent Medicines to understand the work behind the compilation.

Combined tazemetostat and MAPKi enhances differentiation of papillary thyroid cancer cells harbouring BRAFV600E by synergistically decreasing global trimethylation of H3K27.

Clinical efficacy of differentiation therapy with mitogen-activated protein kinase inhibitors (MAPKi) for lethal radioiodine-refractory papillary thyroid cancer (RR-PTC) urgently needs to be improved and the aberrant trimethylation of histone H3 lysine 27 (H3K27) plays a vital role in BRAFV600E -MAPK-induced cancer dedifferentiation and drug resistance. Therefore, dual inhibition of MAPK and histone methyltransferase (EZH2) may produce more favourable treatment effects. In this study, BRAFV600E -mutant (BCPAP and K1) and BRAF-wild-type (TPC-1) PTC cells were treated with MAPKi (dabrafenib or selumetinib) or EZH2 inhibitor (tazemetostat), or in combination, and the expression of iodine-metabolizing genes, radioiodine uptake, and toxicity were tested. We found that tazemetostat alone slightly increased iodine-metabolizing gene expression and promoted radioiodine uptake and toxicity, irrespective of the BRAF status. However, MAPKi induced these effects preferentially in BRAFV600E mutant cells, which was robustly strengthened by tazemetostat incorporation. Mechanically, MAPKi-induced decrease of trimethylation of H3K27 was evidently intensified by tazemetostat in BRAFV600E -mutant cells. In conclusion, tazemetostat combined with MAPKi enhances differentiation of PTC cells harbouring BRAFV600E through synergistically decreasing global trimethylation of H3K27, representing a novel differentiation strategy.

Clinicopathological Features Predict Outcomes in Patients with Radioiodine-Refractory Differentiated Thyroid Cancer Treated with Sorafenib: A Real-World Study.

BACKGROUND: Because beneficial response and progression-free survival (PFS) were achieved by well-designed clinical trials with tyrosine kinase inhibitors (TKIs) in patients with progressive radioiodine-refractory differentiated thyroid cancer (RR-DTC), the overall survival (OS) and improvement of therapeutic outcomes in the real world have been anticipated. SUBJECTS, MATERIALS, AND METHODS: This prospective, single-center, real-world study assessed the predictive significance of clinicopathological features on disease control rate (DCR), objective response rate (ORR), PFS, and OS in a cohort of 72 patients with progressive RR-DTC treated with sorafenib at an initial dose of 200 mg twice daily. RESULTS: Disease control, objective response, and biochemical effectiveness were achieved in 73.3%, 21.7%, and 77.9% of patients, respectively. The median PFS and OS were 17.6 and 28.9 months, respectively. Multivariate analyses showed that hand-foot syndrome (HFS) was an independent predictor for better DCR and ORR, and 131 I-avidity for higher ORR. In univariate analyses, longer PFS and OS were observed in patients with Eastern Cooperative Oncology Group performance status (ECOG PS) ≤2, pathologically well DTC, lung-only metastasis, absence of bone metastasis, biochemically nonineffective response, HFS, or radiological disease control. In multivariate analyses, only well DTC and ECOG PS ≤2 remained as independent prognostic factors for more favorable PFS and OS, respectively, whereas the absence of bone metastasis and biochemically nonineffective response independently predicted superior PFS and OS. CONCLUSION: This study demonstrated that clinicopathological features might play a vital role in predicting therapeutic outcomes in patients with progressive RR-DTC treated with sorafenib, warranting further optimization of candidates for TKIs. IMPLICATIONS FOR PRACTICE: This prospective, single-center, real-world study was designed to investigate the significance of clinicopathological features in predicting response, progression-free survival, and overall survival in patients with progressive radioiodine-refractory differentiated thyroid cancer (DTC) treated with sorafenib. Multivariate analyses showed that hand-foot syndrome was an independent predictor for better response. Meanwhile, well DTC, Eastern Cooperative Oncology Group performance status ≤2, biochemically nonineffective response, and the absence of bone metastasis were independent prognostic factors for more favorable survival. This study demonstrated that clinicopathological features might play a vital role in predicting outcomes in sorafenib-treated patients with radioiodine-refractory DTC, warranting optimization of indications.

The clinical benefits of Chinese patent medicines against COVID-19 based on current evidence.

The outbreak of emerging infectious pneumonia caused by 2019 Novel Coronavirus (2019-nCoV) has posed an enormous threat to public health, and traditional Chinese medicine (TCM) have made vast contribution to the prevention, treatment and rehabilitation of coronavirus disease 19 (COVID-19) among Chinese population. As an indispensable part of TCM, Chinese patent medicines (CPMs) are highly valued and critically acclaimed in their campaign to contain and tackle the epidemic, they can achieve considerable effects for both suspected cases under medical observation period, and confirmed individuals with serious underlying diseases or critical conditions. Given this, based on the Guideline on Diagnosis and Treatment of Coronavirus Disease 2019 in China, the present review summarized the basic information, clinical evidence and published literatures of recommended CPMs against COVID-19. The details were thoroughly introduced involving compositions, therapeutic effects, clinical indications, medication history of CPMs and the profiles of corresponding research. With regard to infected patients with different stages and syndrome, the preferable potentials and therapeutic mechanism of CPMs were addressed through the comprehensive collection of relevant literatures and on-going clinical trials. This study could provide an insight into clinical application and underlying mechanism of recommended CPMs against COVID-19, with the aim to share the Chinese experience in clinical practice and facilitate scientific development of TCM, especially CPMs in the fierce battle of COVID-19.

Long-term clinical outcomes of everolimus-eluting stent versus paclitaxel-eluting stent in patients undergoing percutaneous coronary interventions: a meta-analysis.

BACKGROUND: Everolimus -eluting stent (EES) is common used in patients undergoing percutaneous coronary interventions (PCI). Our purpose is to evaluate long-term clinical outcomes of everolimus -eluting stent (EES) versus paclitaxel-eluting stent (PES) in patients undergoing percutaneous coronaryinterventions (PCI) in randomized controlled trials (RCTs). METHODS: We searched Medline, EMBASE, Cochrane Library, CNKI, VIP and relevant websites ( https://scholar-google-com.ezproxy.lib.usf.edu/ ) for articles to compare outcomes between everolimus-eluting stent and paclitaxel-eluting stent without language or date restriction. RCTs that compared the use of everolimus -eluting stent and paclitaxel-eluting stent in PCI were included. Variables relating to patient, study characteristics, and clinical endpoints were extracted. Meta-analysis was performed using RevMan 5.2 software. RESULTS: We identified 6 published studies (from three randomized trials) more on everolimus-eluting stent (n = 3352) than paclitaxel-eluting (n = 1639), with follow-up duration ranging from 3, 4 and 5 years. Three-year outcomes of everolimus-eluting stent compared to paclitaxel-eluting were as following: the everolimus-eluting stent significantly reduced all-cause death (relative risk [RR]:0.63; 95% confidence interval [CI]: 0.46. to 0.82), MACE (RR: 0.56; 95% CI: 0.41 to 0.77), MI (RR: 0.64; 95% CI: 0.48 to 0.86), TLR (RR: 0.72; 95% CI: 0.59 to 0.88), ID-TLR (RR: 0.74; 95% CI: 0.59 to 0.92) and ST (RR: 0.54; 95% CI: 0.32 to 0.90). There was no difference in TVR between the everolimus-eluting and paclitaxel-eluting (RR: 0.76; 95% CI: 0.58 to 1.10); Four-year outcomes of everolimus-eluting compared to paclitaxel-eluting: the everolimus-eluting significantly reduced MACE (RR: 0.44; 95% CI: 0.18 to 0.98) and ID-TLR (RR: 0.47; 95 % CI: 0.23 to 0.97). There was no difference in MI (RR: 0.48; 95% CI: 0.16 to 1.46), TLR (RR: 0.46; 95% CI: 0.20 to 1.04) and ST ((RR: 0.34; 95% CI: 0.05 to 2.39). Five-year outcomes of everolimus-eluting stent compared to paclitaxel-eluting: There was no difference in ID-TLR (RR: 0.67; 95% CI: 0.45 to 1.02) and ST (RR: 0.71; 95% CI: 0.28 to 1.80). CONCLUSIONS: In the present meta-analysis, everolimus-eluting appeared to be safe and clinically effective in patients undergoing PCI in comparison to PES in 3-year clinical outcomes; there was similar no difference in reduction of ST between EES and PES in long-term(≥ 4 years) clinical follow-ups. Everolimus-eluting is more safety than paclitaxel-eluting in long-term clinical follow-ups, whether these effects can be applied to different patient subgroups warrants further investigation.

Predicting T-Cell Lymphoma in Children From 18F-FDG PET-CT Imaging With Multiple Machine Learning Models.

This study aimed to examine the feasibility of utilizing radiomics models derived from 18F-FDG PET/CT imaging to screen for T-cell lymphoma in children with lymphoma. All patients had undergone 18F-FDG PET/CT scans. Lesions were extracted from PET/CT and randomly divided into training and validation sets. Two different types of models were constructed as follows: features that are extracted from standardized uptake values (SUV)-associated parameters, and CT images were used to build SUV/CT-based model. Features that are derived from PET and CT images were used to build PET/CT-based model. Logistic regression (LR), linear support vector machine, support vector machine with the radial basis function kernel, neural networks, and adaptive boosting were performed as classifiers in each model. In the training sets, 77 patients, and 247 lesions were selected for building the models. In the validation sets, PET/CT-based model demonstrated better performance than that of SUV/CT-based model in the prediction of T-cell lymphoma. LR showed highest accuracy with 0.779 [0.697, 0.860], area under the receiver operating characteristic curve (AUC) with 0.863 [0.762, 0.963], and preferable goodness-of-fit in PET/CT-based model at the patient level. LR also showed best performance with accuracy of 0.838 [0.741, 0.936], AUC of 0.907 [0.839, 0.976], and preferable goodness-of-fit in PET/CT-based model at the lesion level. 18F-FDG PET/CT-based radiomics models with different machine learning classifiers were able to screen T-cell lymphoma in children with high accuracy, AUC, and preferable goodness-of-fit, providing incremental value compared with SUV-associated features.

Epigenetic Targets and Their Inhibitors in Thyroid Cancer Treatment.

Although biologically targeted therapies based on key oncogenic mutations have made significant progress in the treatment of locally advanced or metastatic thyroid cancer, the challenges of drug resistance are urging us to explore other potentially effective targets. Herein, epigenetic modifications in thyroid cancer, including DNA methylation, histone modifications, non-coding RNAs, chromatin remodeling and RNA alterations, are reviewed and epigenetic therapeutic agents for the treatment of thyroid cancer, such as DNMT (DNA methyltransferase) inhibitors, HDAC (histone deacetylase) inhibitors, BRD4 (bromodomain-containing protein 4) inhibitors, KDM1A (lysine demethylase 1A) inhibitors and EZH2 (enhancer of zeste homolog 2) inhibitors, are updated. We conclude that epigenetics is promising as a therapeutic target in thyroid cancer and further clinical trials are warranted.

[Study on the dynamic variations of Z-ligustilide and n-butylidenephthalide content in essential oil of radix angelicae sinensis from different growth period].

OBJECTIVE: To study the variation of the biomass of the root and active components of Angelica sinensis during different growth periods. METHODS: 27 batches of Angelica sinensis were harvested from different growth periods, and the biomass of underground parts were determined; The Gas Chromatography-Mass Spectrometry (GC-MS) was used for determining the contents of Z-ligustilide and n-Butylidenephthalide in essential oil of Radix Angelicae Sinensis. RESULTS: The average contents of n-Butylidenephthalide and Z-ligustilide were more than 1% and 40% in the total essential oil of Radix Angelicae sinensis respectively. Their contents showed larger difference during different growth period. CONCLUSION: The contents of Z-ligustilide and n-Butylidenephthalide of Radix Angelicae Sinensis is closely related to their growth period.

Real-world insights into the efficacy and safety of tyrosine kinase inhibitors against thyroid cancers.

Based on clinical trials demonstrating favorable short-term efficacy and tolerable toxicity, several tyrosine kinase inhibitors have been approved for treating locally recurrent or metastatic, progressive radioiodine-refractory differentiated thyroid cancer, BRAFV600E-mutant anaplastic thyroid cancer, and advanced or progressive medullary thyroid cancer. Longer term efficacy and safety of these treatments have been investigated in multiple real-world studies, demonstrating indispensable complementary value. Hereby, we summarize data from a total of 27 real-world studies with a focus on long-term survival data and rare but life-threatening adverse effects. An overall picture of current real-world study was drawn, and integrated experience of multiple centers would be helpful to clinical practice and further research.

Initial or salvage treatment with apatinib shows promise against radioiodine-refractory differentiated thyroid carcinoma.

OBJECTIVE: Sorafenib and lenvatinib have been recommended as standard tyrosine kinase inhibitors (TKIs) for progressive radioiodine-refractory differentiated thyroid carcinoma (RR-DTC). However, their efficacy remains limited with unresolved drug resistance. Therefore, we conceived this open-label study based on real-world evidence to investigate the efficacy and safety of apatinib in patients with progressive RR-DTC. METHODS: Off-label use of apatinib as either initial treatment or salvage treatment for sorafenib resistance was investigated. The primary endpoint was progression-free survival (PFS) and the secondary endpoints included objective response rate (ORR), overall survival (OS), and safety. RESULTS: For all 28 enrolled patients, the median PFS was 15.1 months, with an ORR of 69.6%. The median OS was not reached at the data cut-off. In detail, the median PFS of 17.3 months and the ORR of 75% were determined in patients with TKI-naive RR-DTC (initial treatment group, n = 14). And, in patients with first-line sorafenib-resistant RR-DTC (salvage treatment group, n = 14), a median PFS of 12.0 months was reached, with an ORR of 45.5%. In the salvage treatment group, the median OS from the start of apatinib administration was 20.6 months, reaching 89.1 months from sorafenib treatment initiation. Adverse events at grade 3 or higher occurred in 64.3% of all subjects treated with apatinib. CONCLUSIONS: This study demonstrated that apatinib shows promise against RR-DTC with tolerable toxicity, representing a novel initial treatment for progressive RR-DTC and effective salvage treatment for RR-DTC resistant to sorafenib.

Targeting IGF2BP2 Promotes Differentiation of Radioiodine Refractory Papillary Thyroid Cancer via Destabilizing RUNX2 mRNA.

N6-methyladenosine (m6A) regulators play an important role in multiple biological and pathological processes of radioiodine refractory papillary thyroid cancer (RR-PTC). However, the function of m6A regulators in differentiation of RR-PTC remains unclear. In this study, online data, clinical samples, and RR-PTC cell lines (K1 and TPC1) were used to identify the m6A regulators that contributed to the differentiation of RR-PTC. Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) was found to be associated with thyroid-specific genes in online data analyses, and metastatic PTCs with high expression of IGF2BP2 were prone to be 131I-nonavid in clinical analyses. Furthermore, targeting IGF2BP2 increased 125I uptake in RR-PTC cell lines and enhanced the sodium/iodide symporter (NIS) expression. Mechanistically, IGF2BP2 bound to the m6A modification site of runt-related transcription factor 2 (RUNX2) 3'-UTR and enhanced the RUNX2 mRNA stability. Moreover, RUNX2 could bind to the promoter region of NIS to block the differentiation of RR-PTC. Together, these results demonstrated that IGF2BP2 represents a diagnostic marker for RR-PTC, suggesting a novel differentiation therapeutic strategy of targeting IGF2BP2.

ERBB2 as a prognostic biomarker correlates with immune infiltrates in papillary thyroid cancer.

Epidermal growth factor receptor 2 (ERBB2) is commonly over-expressed in advanced or metastatic tissues of papillary thyroid cancer (PTC) with poor prognosis, while it remains unknown whether ERBB2 plays a role in the progression of PTC. Thus, we analyzed the data derived from online repositories, including TCGA, KEGG, GO, GeneMANIA, and STRING, to explore the relationship between ERBB2 expression and prognosis, tumor phenotypes of interest, and immune infiltrates in PTC. Compared to normal thyroid tissue, ERBB2 was up-regulated in PTC samples (p < 0.001); In comparison with the group with low expression of ERBB2, the group with high expression of ERBB2 had poorer progression-free interval in stage III/IV patients (p = 0.008) and patients aged >45 years (p = 0.019). The up-regulated ERBB2 was associated with iodine metabolism dysfunction, proliferation, metastasis, angiogenesis, and drug resistance. The expression of ERBB2 negatively correlated with enrichment scores of B cells (r = -0.176, p < 0.001), CD8+ T cells (r = -0.160, p < 0.001), cytotoxic cells (r = -0.219, p < 0.001), NK CD56dim cells (r = -0.218, p < 0.001), plasmacytoid dendritic cells (r = -0.267, p < 0.001), T cells (r = -0.164, p < 0.001), T follicular helper cells (r = -0.111, p = 0.012), gamma delta T cells (r = -0.105, p = 0.017), and regulatory T cells (r = -0.125, p = 0.005). In conclusion, ERBB2 may serve as a prognostic biomarker and an immunotherapeutic target in PTC, deserving further exploration.

IGF2BP2-dependent activation of ERBB2 signaling contributes to acquired resistance to tyrosine kinase inhibitor in differentiation therapy of radioiodine-refractory papillary thyroid cancer.

Acquired drug resistance represents a major obstacle to tyrosine kinase inhibitor (TKI)-induced differentiation therapy of radioiodine-refractory papillary thyroid cancer (RR-PTC); thus, there is an urgent need to elucidate the underlying mechanisms. Here, selumetinib-resistant PTC (PTCSR) cell lines, which were characterized by loss of sodium/iodide symporter expression, enhanced insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2), and activated V-Erb-B2 avian erythroblastic leukemia viral oncogene homolog 2 (ERBB2) signaling, were initially established using a dose escalation method. Upon knockdown of IGF2BP2 in PTCSR cells, ERBB2 signaling was inhibited, and the acquired drug resistance was partially reversed. Mechanistically, the luciferase activity assay showed that IGF2BP2 bound to the N6-methyladenosine-binding site in the coding sequence of ERBB2 mRNA, yielding an increased ERBB2 translation efficacy revealed by polysome profiling. Inhibition of ERBB2 and IGF2BP2 by lapatinib robustly rescued the PTCSR cells from acquired dedifferentiation. Our study demonstrated that IGF2BP2-dependent ERBB2 signaling activation contributes to acquired resistance to TKI, which may be a promising differentiation strategy for RR-PTC by targeting IGF2BP2.

Diagnosis and Treatment of Acute Pleural Effusion following Radioiodine Remnant Ablation Post Lobectomy for Thyroid Cancer.

Radioiodine remnant ablation (RRA) was previously demonstrated to be a safe and effective alternative to completion thyroidectomy for patients with differentiated thyroid cancer (DTC). However, its side effects have not been fully investigated, particularly in patients with lobectomy. We reported a young euthyroidal female who underwent RRA post lobectomy and lymph node dissection for papillary thyroid cancer, whose post-ablation 131I-whole-body scan accidentally showed diffuse radioiodine distribution on chest-mimicking pulmonary metastases. Immediately-added single-photon emission computed tomography/computed tomography (SPECT/CT), nevertheless, revealed a 131I-accumulating swollen left thyroid lobe and emerging pleural effusion, which relieved after short-term treatment with prednisone. In summary, acute pleural effusion ascribed to RRA-induced thoracic duct compression was reported for the first time. 131I-lobectomy-induced pleural effusion could be precisely diagnosed by SPECT/CT and efficiently manipulated via treating radiation thyroiditis with the short-term administration of corticosteroid.