Therapy For Thyroid Cancer Research Articles

Lenvatinib as a salvage therapy for advanced metastatic medullary thyroid cancer.

Patients with advanced progressive metastatic medullary thyroid cancer (MTC), show poor prognosis and few available systemic therapeutic options. After the loss of clinical benefit with other tyrosine kinase inhibitors (TKI), we evaluated the use of lenvatinib as salvage therapy. Ten patients who experienced the loss of clinical benefit after treatment with at least one previous TKI, were treated with lenvatinib. We assessed patient's response immediately before, at the first (first-EV) and last (last-EV) evaluation, after the beginning of treatment. At first-EV, one patient died, while all the remaining 9 showed a stable disease (SD) in the target lesions. At last-EV, SD was still observed in seven patients, while partial response (PR) and progressive disease (PD), in one patient each. Conversely, analyzing all target and non-target lesions, at first-EV, we observed PR in one patient and SD in eight patients. At last-EV, PR was shown in two patients and SD was shown in seven. Bone metastases showed stable disease control at both first-EV and last-EV in only approximately 60% of cases. Tumor markers (CTN and CEA) decreased at first-EV, while they increased at last-EV. Seven patients experienced at least one dose reduction during treatment with lenvatinib. In this real-life clinical experience, lenvatinib showed interesting results as salvage therapy in patients with advanced progressive metastatic MTC patients. Its usefulness could be effective in patients without any other available treatment, because previously used or unsuitable, especially with negative RET status with no access to the new highly selective targeted therapies.

Knockdown of eIF3a attenuated cell growth in K1 human thyroid cancer cells.

In ribosome establishment and the initiation of translation, eukaryotic translation initiation factor (eIF) 3a is a pivotal functional subunit of the eIF3 complex. In various cancer types, abnormal eIF3a expression plays an important role in tumorigenesis. We aimed to explore the role of eIF3a in human thyroid cancer (TC). The expression of eIF3a was determined in TC tissues by qRT-PCR and immunohistochemistry (IHC) assay, respectively. In addition, the expression of eIF3a in K1 and BCPAP cells were detected by qRT-PCR. Cell proliferation, cell cycle, and cell apoptosis were assessed after eIF3a knockdown in K1 in cell line. The expression of eIF3a mRNA was high in TC tissues and cancer cell lines. Moreover, eIF3a expression in TC tissues indicated that high eIF3a level was associated with tumor grade. In addition, eIF3a knockdown resulted in a significantly decrease in cell proliferation and increased the apoptosis of K1 cells. Cell cycle was arrested in both the S and G2/M phase. The levels of phosphorylated ERK1/2 and surviving were decreased after eIF3a knockdown. Our study suggested that eIF3a contributed to TC cell proliferation. It may be a promising target for gene therapy in human thyroid cancer.

Thyroid Carcinoma: Phenotypic Features, Underlying Biology and Potential Relevance for Targeting Therapy.

Thyroid carcinoma consists a group of phenotypically heterogeneous cancers. Recent advances in biological technologies have been advancing the delineation of genetic, epigenetic, and non-genetic factors that contribute to the heterogeneities of these cancers. In this review article, we discuss new findings that are greatly improving the understanding of thyroid cancer biology and facilitating the identification of novel targets for therapeutic intervention. We review the phenotypic features of different subtypes of thyroid cancers and their underlying biology. We discuss recent discoveries in thyroid cancer heterogeneities and the critical mechanisms contributing to the heterogeneity with emphases on genetic and epigenetic factors, cancer stemness traits, and tumor microenvironments. We also discuss the potential relevance of the intratumor heterogeneity in understanding therapeutic resistance and how new findings in tumor biology can facilitate designing novel targeting therapies for thyroid cancer.

Molecular-Driven Therapy in Advanced Thyroid Cancer.

With a growing understanding of the biologic drivers of different thyroid cancers, there is an ongoing revolution in the treatment of aggressive and advanced disease variants. This includes matching patients with specific point mutations or gene fusions to targeted therapies (e.g., selective RET inhibitors), delineating patients who are likely to respond to immune checkpoint inhibition (i.e., PD-L1-positive tumors) and even priming responses to traditional therapies such as radioactive iodine (via concomitant MAPK pathway inhibition). There is also a growing role for genomics in the prognostication of thyroid tumors to aid the adjudication of appropriate treatments. Taking stock of the current state of the field, recent successes should be celebrated, but there still remains a long road ahead to improve outcomes for patients, particularly for radioactive-iodine refractory differentiated thyroid cancer and anaplastic thyroid cancer. In this review, we summarize findings from recent clinical trials and highlight promising preclinical data supporting molecular-driven therapy in advanced thyroid cancer. Ultimately, enrollment in clinical trials remains paramount to the advancement of thyroid cancer care.

The detection of SAS1B in serum provides clues for early diagnosis of thyroid cancer.

The incidence of thyroid cancer is rising globally. Most patients progress slowly, but some patients develop lymph node and distant metastasis earlier, and their prognosis is poor. Therefore, early diagnosis and warning of malignancy are very meaningful for such patients. SAS1B gene is a newly discovered protein expressed on the surface of mature egg cells and has metalloendopeptidase activity. We aimed at exploring whether SAS1B is involved in the occurrence of thyroid cancer, and at providing evidence for early diagnosis and targeted therapy of thyroid cancer. In this study, a rabbit anti-human SAS1B polyclonal antibody was prepared by gene recombination technology. The indirect ELISA method was used to detect the SAS1B protein expression in the serum of 69 patients with thyroid cancer and 55 normal controls, and the relevant pathological factors were analyzed. Immunohistochemistry and PCR technology were used to investigate the expression levels of SAS1B protein and mRNA in 30 thyroid cancer tissues and 23 control thyroid tissues. The titer of SAS1B recombinant antibody was 1:51200. The expression of SAS1B in the serum of patients with thyroid cancer was higher than that in the normal control group (p<0.01). The antibody had a good sensitivity in serum detection of cancer patients (p=0.008<0.01), the linear regression analysis result was that the expression of SAS1B gene was related to tumor envelope invasion and lymph node metastasis (p=0.003<0.01, p=0.003<0.01), and it was irrelevant to the patient's gender, age, tumor mass size, number of cancer foci, pathological stage, etc. (p>0.05). The results of immunohistochemistry showed that SAS1B protein was mainly located in the cytoplasm and membrane of thyroid cancer cells. The expression intensity in thyroid cancer tissues was higher than that in control tissues (p<0.05), but it was not expressed in normal thyroid tissues. Antibodies showed a good sensitivity that was used to detect thyroid cancer tissues (p=0.000<0.01). The results of ordinary PCR detection using thyroid cancer tissue and control thyroid tissue showed that the amplification products of the three domains (N-terminal, C-terminal and catalytic domain) of the SAS1B gene showed high expression in thyroid cancer tissue. q-PCR results showed that the expression of SAS1B gene in thyroid cancer and control thyroid tissue was higher than that in control group (p<0.05), and the genes of Aurora A and BARD1 related to centrosome replication and DNA replication forks protection during the proliferation were highly expressed in thyroid cancer tissue. The study results suggested that SAS1B was involved in the carcinogenesis of thyroid cancer. The Hum_mPLoc.2.0 software, PSORT Ⅱ software and UniProt software were used to predict that SAS1B protein had secretory protein properties. The above data indicate that the SAS1B gene is closely related to the process of thyroid cancer and can serve as a good tumor marker that can be used for early diagnosis and early warning of thyroid malignancy.

Tunicamycin as a Novel Redifferentiation Agent in Radioiodine Therapy for Anaplastic Thyroid Cancer.

The silencing of thyroid-related genes presents difficulties in radioiodine therapy for anaplastic thyroid cancers (ATCs). Tunicamycin (TM), an N-linked glycosylation inhibitor, is an anticancer drug. Herein, we investigated TM-induced restoration of responsiveness to radioiodine therapy in radioiodine refractory ATCs. 125I uptake increased in TM-treated ATC cell lines, including BHT101 and CAL62, which was inhibited by KClO4, a sodium-iodide symporter (NIS) inhibitor. TM upregulated the mRNA expression of iodide-handling genes and the protein expression of NIS. TM blocked pERK1/2 phosphorylation in both cell lines, but AKT (protein kinase B) phosphorylation was only observed in CAL62 cells. The downregulation of glucose transporter 1 protein was confirmed in TM-treated cells, with a significant reduction in 18F-fluorodeoxyglucose (FDG) uptake. A significant reduction in colony-forming ability and marked tumor growth inhibition were observed in the combination group. TM was revealed to possess a novel function as a redifferentiation inducer in ATC as it induces the restoration of iodide-handling gene expression and radioiodine avidity, thereby facilitating effective radioiodine therapy.

Characterization of LDD-2633 as a Novel RET Kinase Inhibitor with Anti-Tumor Effects in Thyroid Cancer.

Rearranged during transfection (RET), a receptor tyrosine kinase, is activated by glial cell line-derived neurotrophic factor family ligands. Chromosomal rearrangement or point mutations in RET are observed in patients with papillary thyroid and medullary thyroid carcinomas. Oncogenic alteration of RET results in constitutive activation of RET activity. Therefore, inhibiting RET activity has become a target in thyroid cancer therapy. Here, the anti-tumor activity of a novel RET inhibitor was characterized in medullary thyroid carcinoma cells. The indirubin derivative LDD-2633 was tested for RET kinase inhibitory activity. In vitro, LDD-2633 showed potent inhibition of RET kinase activity, with an IC50 of 4.42 nM. The growth of TT thyroid carcinoma cells harboring an RET mutation was suppressed by LDD-2633 treatment via the proliferation suppression and the induction of apoptosis. The effects of LDD-2633 on the RET signaling pathway were examined; LDD-2633 inhibited the phosphorylation of the RET protein and the downstream molecules Shc and ERK1/2. Oral administration of 20 or 40 mg/kg of LDD-2633 induced dose-dependent suppression of TT cell xenograft tumor growth. The in vivo and in vitro experimental results supported the potential use of LDD-2633 as an anticancer drug for thyroid cancers.

Hormonal Replacement Therapy and Risk of Thyroid Cancer in Women: A Meta-Epidemiological Analysis of Prospective Cohort Studies.

ObjectivesMany experimental studies have reported that female sex hormones involve thyroid cancer development because the incidence rate of thyroid cancer in women (TCW) is 3 times higher than in men. Three previous systematic reviews reporting no association between hormone replacement therapy (HRT) and TCW risk had the same search year of 2014. The aim was to reevaluate the association between HRT use and TCW risk using a meta-epidemiological study of prospective cohort studies.MethodsThe study preferentially used all studies selected by the existing systematic reviews and then secured an additional cohort from the list citing the studies. The selection criterion was defined as the prospective cohort study assessing the association between HRT and TCW risk by adjusted relative risk and its 95% confidence intervals (CI) from multivariate analysis. A random-effects model meta-analysis was applied to estimate summary relative risk (sRR) and its 95% CI. A publication bias was evaluated by Egger’s test; moreover, the statistical significance level was set at 5%.ResultsNine cohort studies were finally selected. The random-effect model was applied because of heterogeneity (I2 = 64.3%). The sRR and its 95% CI from a random-effects model meta-analysis had no statistical significance in the association between HRT and TCW risk (sRR = 1.11; 95% CI, 0.98–1.26). Additionally, Egger’s test revealed no statistical significance (P = 0.91).ConclusionsHRT is not associated with TCW risk based on the random-effects model meta-analysis of prospective cohort studies published until now.

Synthesis and characterization of CD133 targeted aptamer-drug conjugates for precision therapy of anaplastic thyroid cancer.

Anaplastic thyroid cancer (ATC) is an undifferentiated and highly aggressive type of thyroid cancer and is extremely resistant to standard therapies such as surgical resection and radioactive iodine therapy. Although targeted therapeutic agents including small molecule drugs and monoclonal antibodies are rapidly developed in recent years, no ATC targeted drugs are available to date; thereby, novel targeted therapies are needed to improve the outcomes of ATC patients. Aptamers are single-stranded DNA (or RNA) molecules that can selectively bind to cancer specific antigens, and aptamer-based targeted therapy has certain advantages over that based on antibodies due to its high binding affinity and low immunogenicity. Here, we identified that CD133, a cancer stem cell marker, was specifically expressed in ATC tumor tissues and cells, implying that CD133 is a potential drug target for ATC therapy. Additionally, we successfully obtained a CD133 targeted aptamer AP-1 by paired cell-based SELEX, which can precisely recognize CD133 antigen in vitro. Furthermore, the truncated AP-1-M aptamer from its precursor AP-1 has shown higher binding affinity for CD133, and specifically accumulated in anaplastic thyroid cancer FRO cell derived tumor in vivo. Conjugation of truncated AP-1-M with doxorubicin could dramatically inhibit CD133 positive FRO cell proliferation, induce cell apoptosis in vitro, and also suppress tumor growth in FRO cell xenograft mice in vivo. Our results clearly demonstrated that the CD133 targeted aptamer AP-1-M conjugated with anticancer drugs has potential to become a promising therapeutic approach against ATC in the near future.

Early Quantification of Salivary Gland Function after Radioiodine Therapy.

Purpose of the Study:Radioiodine (I-131) is used as an effective noninvasive treatment for thyroid malignancies. Salivary gland is one of the most affected nontarget organs. The present study aims to perform early quantification of salivary gland function after I-131 therapy (RIT) for thyroid cancer considering I-131 down-scatter in the Tc-99m window.Materials and Methods:A total of 20 patients (6 males and 14 females) with differentiated thyroid carcinoma were enrolled in the study. Baseline dynamic salivary scintigraphy was performed in all patients using 185–370 MBq (5–10 mCi) Tc-99m pertechnetate. Posttherapy, salivary scintigraphy was performed 10–25 days after RIT in the range of 1.85–7.4 GBq (50–200 mCi). Time–activity curves obtained from the pre- and posttherapy dynamic salivary scintigraphy were used for semi-quantitative analysis. Uptake ratio (UR), ejection fraction (EF%), and maximum accumulation (MA%) were calculated by drawing regions of interest of individual parotid and submandibular glands over a composite image, after correcting for down-scatter from I-131 in the Tc-99m window. A paired t-test was used for comparison of the parameters obtained.Results:Significant changes were observed in UR and EF% of both parotid and submandibular glands (P < 0.05). No significant changes were found in the value of MA% of left parotid gland and both submandibular glands in the posttherapy scans in comparison to pretherapy scans (P > 0.05). However, significant difference was observed in the MA% of the right parotid gland (P = 0.025).Conclusion:Salivary gland function was found to deteriorate after RIT, with the parotid glands affected more than the submandibular glands.

Molecular targeted therapy for thyroid cancer: How to manage adverse events and optimize dose modifications

Molecular targeted therapy for thyroid cancer: How to manage adverse events and optimize dose modifications

Selenium nanoparticles coated with pH responsive silk fibroin complex for fingolimod release and enhanced targeting in thyroid cancer

Cancer-targeted drug delivery systems based on nanoparticles (NPs) have been considered promising therapies. In this study, we developed a pH-responsive smart NPs drug delivery system using silk fibroin (SF), selenium nanoparticles (Se NPs), fingolimod (FTY720), and heptapeptide (T7). The prepared FTY720@T7-SF-Se NPs were spheres with an average diameter of 120 nm, which would contribute to the enhanced permeability and retention effects in tumour regions. The encapsulation efficiency (EE) of the FTY720@T7-SF-Se NPs was 71.95 ± 3.81%. The release of FTY720 from the nanocarriers was pH-dependent, and the release of FTY720 was accelerated in an acidic environment. Both in vitro and in vivo studies showed that FTY720@T7-SF-Se NPs had an enhanced cellular uptake selectivity and antitumor activity for thyroid cancer. The bio-distribution study in vivo further demonstrated that FTY720@T7-SF-Se NPs could effectively accumulate in the tumour region, thereby enhancing the ability to kill cancer cells in vivo. In addition, studies of histology and immunohistochemistry showed that FTY720@T7-SF-Se NPs had low toxicity to the major organs of tumour-bearing mice, indicating the prepared NPs has good biocompatibility in vivo. These results suggest that the tumour-targeted NPs delivery system (FTY720@T7-SF-Se NPs) has great potential as a new tool for thyroid cancer therapy.

Selective Use of Radioactive Iodine Therapy for Papillary Thyroid Cancers With Low or Lower-Intermediate Recurrence Risk.

Current guidelines recommend a selective use of radioiodine treatment (RAI) for papillary thyroid cancer (PTC). This work aimed to determine how policy changes affect the use of RAI and the short-term outcomes of patients. A retrospective analysis of longitudinal data was conducted in an academic referral center of patients with nonaggressive PTC variants; no extrathyroidal invasion or limited to soft tissues, no distant metastases, and 5 or fewer central-compartment cervical lymph node metastases. In cohort 1, standard treatments were total thyroidectomy and RAI (May 2005-June 2011); in cohort 2 decisions on RAI were deferred for approximately 12 months after surgery (July 2011-December 2018). Propensity score matching was used to adjust for sex, age, tumor size, lymph node status, and extrathyroidal extension. Intervention included immediate RAI or deferred choice. Main outcome measures were responses to initial treatment during 3 or more years of follow-up. In cohort 1, RAI was performed in 50 of 116 patients (51.7%), whereas in cohort 2, it was far less frequent: immediately in 10 of 156 (6.4%), and in 3 more patients after the first follow-up data. The frequencies of structural incomplete response were low (1%-3%), and there were no differences between the 2 cohorts at any follow-up visit. Cohort 2 patients had higher rates of "gray-zone responses" (biochemical incomplete or indeterminate response). Selective use of RAI increases the rate of patients with "uncertain" status during early follow-up. The rate of structural incomplete responses remains low regardless of whether RAI is used immediately. Patients should be made aware of the advantages and drawbacks of omitting RAI.

Parathyroid Hormone Level Changes Following Radioiodine Therapy for Thyroid Cancer: A Prospective Observational Study

ObjectiveOur objective was to analyze the effect of radioiodine (RAI) therapy on parathyroid hormone (PTH) secretion. MethodsA total of 137 patients were included and divided into 2 groups based on pretherapy PTH levels. The residual thyroid tissue volume was classified into 4 grades (0-3), and a value of 0 indicated that there was no apparent residual tissue. We analyzed the PTH level changes among different time points in each group and the factors that could predict the PTH level changes. ResultsIn 113 patients with normal parathyroid gland function, the PTH level at baseline, 1 day, 7 days, 1 month, 3 months, and 6 months after RAI therapy did not show any significant difference; in 24 patients with decreased parathyroid gland function, the level of PTH immediately decreased after the implementation of RAI therapy but gradually returned to a pre-RAI therapy level within 6 months. On the seventh day after therapy, the mean value of PTH in patients with a residual thyroid tissue volume of extent of 0/1 was 8.0 ± 2.3 pg/mL, which was significantly higher than that in patients with a residual thyroid tissue volume of extent of 2/3 (P = .011). Similar phenomena were observed 1 month, 3 months, and 6 months after therapy. ConclusionRAI therapy had a significant transient adverse effect on parathyroid gland function in patients with decreased PTH secretion pretherapy, and the extent was associated with the amount of residual thyroid tissue.

Personalized treatment for differentiated thyroid cancer: current data and new perspectives.

More conservative and personalized treatment options have been developed in recent years to face the rising diagnosis of low-risk differentiated thyroid carcinoma (DTC). The present review describes the change towards a more risk-adapted management either in the treatment or in the follow-up of DTC. Particular attention is given to the innovations introduced by the latest guidelines for low-risk tumors, starting from the most appropriate extension of surgery up to the postoperative management. The emerging role of active surveillance for low-risk microcarcinoma is discussed, as well as the development of percutaneous strategies in the setting of malignant thyroid disease. The recent use of approved new systemic target therapies for advanced radioiodine refractory thyroid cancer is reported, together with the description of new compounds in trial. Finally, we provide some considerations to improve the risk evaluation in a presurgical setting, especially related to the rising role of genetics, to enable better risk-based cancer management and personalized treatment choices.

TREATMENT OF &lt;em&gt;BRAF&lt;/em&gt;&lt;sup&gt;V600E&lt;/sup&gt; POSITIVE ANAPLASTIC THYROID CARCINOMA: CASE REPORT

Anaplastic thyroid cancer is one of the most aggressive and fatal human carcinomas. A significant experience in using various kinase inhibitors for anaplastic thyroid cancer therapy has been accumulated worldwide. The most encouraging results were obtained after using a combination of b-Raf and MEK kinase inhibitors (vemurafenib/dabrafenib and trametinib/cobimetinib, respectively) for the treatment of the unresectable BRAF V600E -positive anaplastic thyroid cancer. This drug combination makes it possible to perform surgery followed by chemoradiotherapy and other targeted therapies. Here we report a clinical case of anaplastic thyroid cancer in a 69-year-old woman, who was treated with neoadjuvant targeted therapy. The treatment was carried out on the basis of three medical institutions: the National Medical Research Radiological Centre (Moscow), the N.I. Pirogov Clinic of Advanced Medical Technologies (St. Petersburg) and the Endocrinology Research Center (Moscow). Since there is still no universal protocol for treating ATC patients, and only palliative therapy is used in most cases, we emphasized on diagnostic and treatment errors of this disease. Special attention was paid to the importance of using molecular diagnostics and modern medical imaging technologies.

Evaluation of Serum Tumor Markers Variation, Following The Radioactive Iodine Therapy in Patients with Differentiated Thyroid Cancer

Introduction: Radioactive iodine is the effective therapy in thyroid cancer. The aim of this study is to evaluate the serum tumor markers in patients under the therapy with radioactive iodine 131. Material and Methods: 45 cases of female patients aged 16-60 years with thyroid cancer surgery referred to the nuclear medicine department of Nemazi hospital for (iodine treatment after surgery) were selected. The selection was on the basis of interviewing and information of patients is consent forms. Only patients with thyroid cancer and referred for the first time without any other diseases were chosen for this study. The selected patients were prescribed a dose of 150 m Ci of I-131. From each patient, 4 mL of chelated serum for serological studies on tumor markers and 2 mL of oxalated serum for spectrophotometry studies on cell death were used in three stages. The first stage before the iodine therapy, the second stage, after 48 hours, and the third stage, 30 days after radioiodine therapy were studied and the results were evaluated by the one-way repeated measures ANOVA test. Results: According to the results of dependent paired T-Test, AFP, in the periods before, 48 hours and 1 month after radioiodine therapy, respectively were 3.46 ± 1.21 and 3.74 ± 1.37 and 3.76 ± 1.25 (p &lt;0.0005). About CA 19-9 in the periods before, 48 hours and one month after radioiodine therapy, the results were 9.30 ± 6.32, 9.95 ± 6.92 (p = 0.040) and 11.26 ± 7.49 (p &lt;0.0005) respectively. About CEA, the results were 1.60 ± 0.60, 1.47 ± 0.55 and 2.23 ± 0.69 (p &lt;0.0005), respectively. In the case of tumor marker CA 15-3 results were 15.53 ± 6.48 and 1.60 ± 0.60 and 15.68 ± 6.52 (p = 0.014), respectively and in the case of ALP, results were 124.22 ± 5 and 122.2 ± 6 and 116.7 ± 7 (p &lt;0.0005), respectively. Conclusion: According to the same studies and the acquired results, it can be concluded that the tumor markers CEA and CA19-9 are more acceptable and sustainable for monitoring the malignancy and progressive disease in patients with thyroid cancer. The decreasing ALP is normal and transient. The increase of AFP and CA15-3 is not even statistically reliable. It is recommended that the period of iodine therapy and falsely elevated tumor markers can be informed to the doctor, during the gastrointestinal studies in patients with thyroid cancer, in order to prevent wrong decisions on the treatment process.

Radioactive iodine treatment of papillary thyroid carcinoma in Japan.

We have a unique history of using radioactive iodine (RAI) therapy and surgical treatment for thyroid cancer in Japan. Less than total thyroidectomy without RAI therapy was the most common management of papillary thyroid carcinoma (PTC) in the past. Limited availability of dedicated facilities for the RAI administration due to the strict regulations and insufficient coverage of the expenses were the major reasons that impacted on the management decisions. Following the publication of the Japanese clinical practice guidelines for thyroid tumors in 2010, the risk-adapted approach has become a standard where the high-risk and selected intermediate-risk PTC patients undergo total thyroidectomy followed by RAI therapy and thyrotropin suppression therapy. We are on the shoulders of pioneers who made every effort to bring the interventions closer to an ideal environment for patients. Armed with the revised clinical practice guidelines 2018 and devised inpatient/outpatient RAI therapy, Japanese physicians are ready to proceed to more rational management that would improve patients' outcomes. Directions for the future include further advancement of relevant clinical research to fill the gaps between current evidence and recommendations in the guidelines, and obtaining approval for high-dose RAI therapy on an outpatient basis to improve its effectiveness in both adjuvant and treatment settings.

A Review of the History of Radioactive Iodine Theranostics: The Origin of Nuclear Ontology

Studies on the first years of radioactive iodine (RAI) use in thyroid diseases have focused on hyperthyroidism. Saul Hertz’s success with RAI in thyrotoxicosis fueled a seamless transition to Samuel Seidlin’s investigations with RAI in thyroid cancer. These landmark events embody nuclear ontology, a philosophical foundation for the creation and existence of radio-therapeutic principles that continue to influence clinical practices today. Laying this ontological foundation, Dr. Saul Hertz who is the founding director of Massachusetts General Hospital Thyroid Clinic, affiliated with Harvard University created a framework for RAI theranostics with preclinical experiments and clinical cases from 1937 to 1942. The first thyroid cancer treatment with RAI was applied in 1942 by Samuel Seidlin. The sensational effect of the first application was interestingly powerful enough to overshadow scientific data. Seidlin and colleagues assembled a sixteen-patient series showcasing a unique entity: functional thyroid metastases that respond to RAI. Other investigations at the time demonstrated that RAI had little efficacy as a therapeutic agent, mainly because most thyroid tumors do not form colloid, and therefore cannot concentrate RAI. These findings were soon overshadowed by a mainstream article in the October 1949 issue of Life that portrayed RAI as a lifesaving therapy for thyroid cancer. The paradigm was set, and later writings by William H. Beierwaltes and other prominent nuclear medicine physicians established the primary goals and principles of RAI therapy. The developments in theoretical physics and nuclear instrumentation and the scientists who made these developments in the early years contributed greatly to the development of the concept. In the field of nuclear medicine, William H. Beierwaltes has gone down in our history as a clinical researcher with his most important contributions. The classical paradigm that started with him has carried us to today’s molecular theranoistic viewpoint. This paper examines controversial topics in the advent of thyroid theranostics, and applies historical significance to current discussions on the role of RAI in thyroid cancer management. Another paradigm shift is on the horizon as thyroidology enters the age of genomics. The molecular theranostic profiles will soon be incorporated into a dynamic clinical decision-making and management algorithm for thyroid surgery and RAI therapy. From now on, nuclear oncology will gain a new ontological identity with molecular pathology and new theranostic expansions.

LINC00106 prevents against metastasis of thyroid cancer by inhibiting epithelial-mesenchymal transition.

Thyroid cancer (TC) is a common malignant tumor of the endocrine system, and its morbidity and mortality are in the high places. Recent studies have focused on exploring biological markers and targeted therapy for TC. This research aims to elucidate the role of LINC00106 in the progression of TC and the regulatory mechanisms. Differential level of LINC00106 in a downloaded profile containing TC and normal tissues from GEPIA database was analyzed. Subsequently, its level in TC tissues and cell lines was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The relationship between LINC00106 level and clinical data of TC patients was assessed, including age, tumor staging, lymphatic metastasis, and overall survival. After transfection of si-LINC00106, TC cell metastasis was evaluated by wound healing and transwell assay. Relative levels of E-cadherin, N-cadherin, β-catenin, and Vimentin regulated by LINC00106 were determined using qRT-PCR and Western blot. LINC00106 was downregulated in TC tissues than normal ones. Its level was correlated to tumor staging, lymphatic metastasis and overall survival in TC patients. The knockdown of LINC00106 in BCPCP and TPC-1 cells enhanced migratory and invasive abilities and triggered the process of epithelial-mesenchymal transition (EMT). LINC00106 is lowly expressed in TC specimens, which attenuates migratory and invasive abilities in TC by inhibiting EMT as a tumor suppressor.