Higher adjuvant radioactive iodine therapy dosage helps intermediate-risk papillary thyroid carcinoma patients achieve better therapeutic effect.

Objective: This retrospective study aims to evaluate the therapeutic effect of varying dosages of adjuvant radioactive iodine (RAI) therapy on intermediate-risk papillary thyroid carcinoma (PTC) patients. Methods: This retrospective study involved a total of 427 intermediate-risk PTC patients, out of which 202 received a 3.7GBq dosage of RAI, and 225 received a 5.55GBq dosage. The evaluation involved assessing the therapeutic outcomes, number of treatment cycles, and successful remnant ablation rates in both dose groups, six months post-adjuvant RAI therapy. Univariate and multivariate logistic regression analyses were employed to identify factors linked with excellent response (ER). Following this, prognostic nomograms were constructed to provide a visual representation of the prediction models. Calibration curves, the concordance index (C-index), and the receiver operating characteristic (ROC) curve were employed to evaluate the predictive performance of these nomograms. The Hosmer-Lemeshow test was applied to assess the models' goodness-of-fit. Additionally, the clinical utility of the prognostic nomograms was appraised through decision curve analysis (DCA). Results: The high-dose (HD) group exhibited significantly higher proportions of ER, single treatment cycles, and successful remnant ablation rates (p<0.05). Being male, receiving a 3.7GBq dose, having an N1b stage, an sTg level ≥10ng/ml, or an sTg/TSH ratio ≥0.11 were independent risk factors for Non-ER. Two prognostic nomograms, "sTg Nomogram" and "sTg/TSH Nomogram", were established. The ranking of factors contributing to ER, in descending order, included the sTg or sTg/TSH ratio, N stage, therapy dosage, sex, and soft tissue invasion. The "sTg/TSH Nomogram" demonstrated a higher C-index compared to the "sTg Nomogram". The calibration curves indicated excellent calibration for both nomograms. DCA demonstrated that the net benefit of the "sTg/TSH Nomogram" was higher than that of the "sTg Nomogram". Conclusion: Higher initial RAI therapy doses can improve therapeutic efficacy for intermediate-risk PTC patients. The developed nomograms, particularly the "sTg/TSH Nomogram", could assist clinicians in optimal therapeutic decision-making.

Evaluating the therapeutic efficacy of radiolabeled BSA@CuS nanoparticle-induced radio-photothermal therapy against anaplastic thyroid cancer.

Bovine serum albumin (BSA) has been employed as a mild biological template in nanoscale particles. Copper sulfide (CuS) has been used for photothermal therapy (PTT) in several studies. In this study, we aimed to synthesize the 131 I-labeled BSA-modified CuS nanoparticles (131 I-BSA@CuS), with attributes of both radiotherapy and PTT, as a therapeutic agent against anaplastic thyroid carcinoma (ATC). BSA@CuS nanoparticles were prepared using the solvothermal reaction and then labeled with Na131 I by the chloramine-T method. The products were characterized and their cytotoxicity was investigated in vitro and in vivo. The therapeutic efficacy of 131 I-BSA@CuS was evaluated in ARO cell (an ATC cell line) subcutaneous tumors. The nanoparticles showed good biocompatibility and low toxicity in vitro and in vivo. BSA@CuS rapidly and effectively converted the light energy from an 808 nm laser into thermal energy with a conversion efficiency of 28.07%. SPECT/CT imaging demonstrated that the accumulation of radioactivity peaked within 24 hr and resided in the tumors for 5 days post intratumoral injection. In vivo assays indicated that, compared to monotherapy, the synthesized nanoparticles employing both PTT and radiotherapy possess better therapeutic efficacy against tumors. The synthesized nanomaterial showed uniform dispersion, good stability and aqueous solubility, excellent photothermal properties, and long-term retention in ATC. Hence, combined radiotherapy and PTT can significantly inhibit tumor growth compared to monotherapy, and can be applied in clinical settings.

Blood prognostic predictors of treatment response for patients with papillary thyroid cancer.

BACKGROUND: Papillary thyroid cancer (PTC) is a very common malignant disease with high morbidity. We needed some pretreatment indicators to help us predict prognosis and guide treatment. We conducted a study about some pretreatment prognostic indicators. METHODS: This clinical study recruited 705 postoperative PTC patients (211 males, 494 females). Clinical data before radioactive iodine (RAI) treatment were collected. Patients' response to therapy were classified into two categories: 'Good Prognosis Group' (GPG) and 'Poor Prognosis Group' (PPG), according to '2015 American Thyroid Association Guidelines'. Differences of indicators between different prognosis groups were compared. Odds ratios (ORs) were calculated by univariate/multiple binary logistic regression models. Difference of body mass index (BMI) changes before and after RAI treatment between different prognosis groups was also compared. RESULTS: A total of 546 (77.45%) belonged to GPG, and 159 (22.55%) belonged to PPG. Platelet (PLT), neutrophil (NEUT), PLT subgroups, and combination of red blood cell distribution width (RDW) and BMI (COR-BMI) were different between two prognosis groups. The significance of the difference between the two groups of BMI disappeared after the Bonferroni correction. PLT and PLT subgroups had detrimental effects on the risk of PPG; T stage had a positive effect on the risk of PPG. PLT subgroup showed a detrimental effect on the risk of PPG when we included additional covariates. CONCLUSIONS: We found that lower pretreatment PLT levels may indicate a poor prognosis for PTC. The relationship between platelet-derived growth factor (PDGF) and radiation sensitivity may be the key to this association.

[Analysis of internal exposure levels of manganese, cobalt, selenium and molybdenum in blood and urine among general population in parts of Shaanxi Province].

OBJECTIVE: To investigate the internal exposure levels of manganese(Mn), cobalt(Co), selenium(Se) and molybdenum(Mo) in blood and urine among the general population in parts of Shaanxi Province, and thereby to analyze their population distribution characteristics. METHODS: In 2017, a total of 720 subjects of general people aged 3-79 years were recruited from 5 counties in Shaanxi Province, by stratified random sampling method, blood and urine samples were collected, and the contents of Mn, Co, Se and Mo in blood and urine samples were detected by inductively coupled plasma mass spectrometry(ICP-MS). The test result were statistically analyzed according to different genders, regions and age groups. RESULTS: Among general people in Shaanxi Province, the median of Mn in blood and urine were separately 8. 43 and 0. 60 µg/L. The median of Mn in blood among males and females were 7. 99 and 8. 81 µg/L, the difference was statistically significant(P<0. 05), the difference of blood Mn between urban and rural areas was statistically significant(P<0. 05). The median of Co in blood and urine were separately 0. 13 and 0. 17 µg/L, the median of Co in blood among males and females were 0. 12 and 0. 15 µg/L, the median of Co in urine among males and females were 0. 16 and 0. 20 µg/L, the differences were statistically significant(P<0. 05), the differences of blood Co and urine Co in urban and rural areas were statistically significant(P<0. 05). The median of Se concentration in blood and urine were separately 73. 20 and 13. 30 µg/L, the median of Se in urine among males and females were 14. 40 and 12. 40 µg/L, the difference were statistically significant(P<0. 05), the differences of blood Se and urine Se in urban and rural areas were statistically significant(P<0. 05). The median of Mo concentration in blood and urine were separately 0. 60 and 50. 40 µg/L, the median of Mo in urine among males and females were 56. 60 and 43. 00 µg/L, the difference was statistically significant(P<0. 05), the difference of blood Mo between urban and rural areas was statistically significant(P<0. 05). Within the same gender, all indexes in whole blood(except female blood Se) were statistically significant among age groups(P<0. 05). The differences of male urine Co, urine Se, urine Mo and female urine Co among age groups were statistically significant(P<0. 05). CONCLUSION: Among general population in Shaanxi Province, the Mn, Co, Se and Mo levels in blood and urine are varied by gender age and area, the blood Se level is relatively low.

Metal-Organic Framework as a Microreactor for in Situ Fabrication of Multifunctional Nanocomposites for Photothermal-Chemotherapy of Tumors in Vivo.

Metal-organic frameworks (MOFs) have been applied in chemotherapeutic drug loading for cancer treatment, but challenging for cases with large and malignant lesions. To overcome these difficulties, combinational therapies of chemotherapy and photothermal therapy (PTT) with potentially high selectivity and slight aggressiveness have drawn tremendous attention to treat various tumors. However, current MOF-based nanohybrids with photothermal agents involve tedious synthesis processes and heterogeneous structures. Herein, we employ MIL-53 as a microreactor to grow polypyrrole (PPy) nanoparticles in situ for the fabrication of PPy@MIL-53 nanocomposites. Fe3+ in MIL-53, as an intrinsic oxidizing agent, can oxidize the pyrrole monomer to generate PPy nanoparticles. The prepared PPy@MIL-53 nanocomposites integrate the intrinsic advantages of MOFs with high drug loading ability and magnetic resonance imaging (MRI) capacity, and PPy nanoparticles with outstanding PTT ability and excellent biocompatibility. The versatile PPy@MIL-53 nanocomposites with multiple functions displayed in vitro and in vivo synergism of photothermal-chemotherapy for cancer, potentially MRI-guided. The proposed MOF microreactor-based synthesis strategy shows a promising prospect in the fabrication of diverse multifunctional nanohybrids for tumor theranostics in vivo.

Influence of the first radioactive iodine ablation on peripheral complete blood count in patients with differentiated thyroid cancer.

Radioactive iodine (RAI) is considered to be related with hematologic changes. This study aimed to evaluate influence of the first RAI ablation on peripheral complete blood count (CBC) in patients with differentiated thyroid cancer (DTC).Data of CBC at baseline and 6 months after RAI were obtained in 385 patients with DTC with approximately 3700 MBq I (ranging 2220-7585 MBq). Further comparison was done in 196 patients with 1-month postablation data available. Routine blood examinations were performed to determine impact of RAI on white blood cell (WBC), red blood cell (RBC), hemoglobin, platelet, neutrophil, lymphocyte, and monocyte in both sexes. Continuous variables were compared by paired t tests and independent samples t test, and categorical variables were compared by chi-square analysis. Data with repeated measurements were analyzed by analysis of variance.The first RAI after thyroidectomy was associated with mild, yet significant declines in WBC, platelet, and lymphocyte, which persisted for 6 months. One month after RAI, significant declines were found in all CBC, including RBC and hemoglobin (all P < 0.05). While CBC partly recovered 6 months after RAI, this follow-up CBC still demonstrated significant declines in WBC, platelet, and lymphocyte (all P < 0.05) without gender differences. Significant rises in RBC and hemoglobin in males and females were found. The decline of platelet in females was more obvious than in males at 3700 to 4440 MBq of RAI. On the contrary, the rises of RBC and hemoglobin in males were higher than in females. There were no significant complications during the follow-up.WBC and platelet decreased obviously 1 month after RAI. While they partly recovered 6 months after RAI, they were still lower than the baseline. However, RBC and hemoglobin transiently decreased at 1 month and then increased to levels even higher than baseline 6 months later. At 3700 to 4440 MBq of RAI, the decline of platelet in females was more obvious than in males. Yet, rises of RBC and hemoglobin in males were higher than in females. The risks associated with these changes are unlikely to outweigh the potential benefits of RAI in patients with DTC.

Different Radioiodine Dose for Remnant Thyroid Ablation in Patients With Differentiated Thyroid Cancer: A Meta-analysis.

OBJECTIVE: Remnant thyroid ablation is crucial in the management of patients with differentiated thyroid cancer. However, the optimal dose of radioactive I for ablation is still controversial. This study aimed to compare the success rate of different activities of I for postoperative remnant ablation in randomized controlled trials (RCTs) and to determine the optimal dose. PATIENTS AND METHODS: Sources were retrieved from the Cochrane Library, Medline, Embase, Scopus, and Google Scholar until March 2014. All RCTs that assessed the efficacy of different doses of I for ablation were selected. After data extraction, statistics were performed by Review Manager 5.2 software. RESULTS: Seventeen RCTs were considered eligible, involving 3737 patients. The overall methodological quality of the studies was good. The rate of successful remnant ablation of low versus moderate I activities (risk ratio [RR], 0.89; 95% confidence interval [CI], 0.80-1.00; P = 0.06) and moderate versus high I activities (RR, 0.94; 95% CI, 0.89-1.00; P = 0.05) showed no significant differences. However, high I activities had 11% higher successful ablation rate than low activities with an RR of 0.89 (95% CI, 0.81-0.97; P = 0.008), which was significant. CONCLUSIONS: We summarized all available randomized evidence to demonstrate that high dose of I was significantly better than low dose to achieve successful remnant thyroid ablation.

Wenxin Keli versus Sotalol for Paroxysmal Atrial Fibrillation Caused by Hyperthyroidism: A Prospective, Open Label, and Randomized Study.

We aimed to compare effectiveness of Wenxin Keli (WK) and sotalol in assisting sinus rhythm (SR) restoration from paroxysmal atrial fibrillation (PAF) caused by hyperthyroidism, as well as in maintaining SR. We randomly prescribed WK (18 g tid) or sotalol (80 mg bid) to 91 or 89 patients. Since it was not ethical not to give patients antiarrhythmia drugs, no control group was set. Antithyroid drugs were given to 90 patients (45 in WK group, 45 in sotalol group); (131)I was given to 90 patients (46 in WK group, 44 in sotalol group). Three months later, SR was obtained in 83/91 or 80/89 cases from WK or sotalol groups (P = 0.762). By another analysis, SR was obtained in 86/90 or 77/90 cases from (131)I or ATD groups (P = 0.022). Then, we randomly assigned the successfully SR-reverted patients into three groups: WK, sotalol, and control (no antiarrhythmia drug was given) groups. After twelve-month follow-up, PAF recurrence happened in 1/54, 2/54, and 9/55 cases, respectively. Log-Rank test showed significant higher PAF recurrent rate in control patients than either treatment (P = 0.06). We demonstrated the same efficacies of WK and sotalol to assist SR reversion from hyperthyroidism-caused PAF. We also showed that either drug could maintain SR in such patients.

Nuclear factor-kappa B inhibition can enhance therapeutic efficacy of 131I on the in vivo management of differentiated thyroid cancer.

AIM: Nuclear factor-kappa B (NF-κB) plays a key role in cancer development and therapy resistance. We aimed to determine whether NF-κB inhibition can enhance (131)I efficacy in differentiated thyroid cancer (DTC) in vivo. MAIN METHODS: Every nude mouse was ip injected with 1mCi of (131)I for thyroid ablation. Four weeks later, DTC cells were implanted. Another six weeks later, mice received four types of therapies, namely control vehicle, 1mCi of (131)I once, 10mg/kg of Bay 11-7082 (a NF-κB inhibitor) trice and combination treatment. Pre-ablation (99m)Tc-pertechnetate imaging, post ablative and post therapeutic imaging were performed. Target-to-background ratios (T/Bs) on xenograft tumors were calculated and compared. Nuclear extract from tumor samples were assessed by DNA-binding assay and Western blot. Apoptotic indices by TUNEL assay were determined and tumor volume curve was drawn to compare therapeutic effects in different groups. KEY FINDINGS: Post therapeutic imaging displayed (131)I-avidity of xenograft tumors and completeness of thyroid ablation. T/Bs comparison showed no significant differences in mice received either (131)I mono-therapy or combined therapy. DNA-binding assay and Western blot showed enhanced function and expression of NF-κB by (131)I, which were inhibited substantially by Bay 11-7082 combination. Apoptotic indices were significantly increased by combined treatment than by any mono-therapy. And DTC lesional volumes were significantly regressed by combined treatment than by any mono-therapy. SIGNIFICANCE: We demonstrated that NF-κB inhibition can be a good interventional avenue to enhance therapeutic potentiation of (131)I on the in vivo management of DTC.

Nuclear factor-kappa B inhibition can enhance apoptosis of differentiated thyroid cancer cells induced by 131I.

OBJECTIVE: To evaluate changes of nuclear factor-kappa B (NF-κB) during radioiodine 131 ((131)I) therapy and whether NF-κB inhibition could enhance (131)I-induced apoptosis in differentiated thyroid cancer (DTC) cells in a synergistic manner. METHODS: Three human DTC cell lines were used. NF-κB inhibition was achieved by using a NF-κB inhibitor (Bay 11-7082) or by p65 siRNA transfection. Methyl-thiazolyl-tetrazolium assay was performed for cell viability assessment. DNA-binding assay, luciferase reporter assay, and Western blot were adopted to determine function and expression changes of NF-κB. Then NF-κB regulated anti-apoptotic factors XIAP, cIAP1, and Bcl-xL were measured. Apoptosis was analyzed by Western blot for caspase 3 and PARP, and by flow cytometry as well. An iodide uptake assay was performed to determine whether NF-κB inhibition could influence radioactive iodide uptake. RESULTS: The methyl-thiazolyl-tetrazolium assay showed significant decrease of viable cells by combination therapy than by mono-therapies. The DNA-binding assay and luciferase reporter assay showed enhanced NF-κB function and reporter gene activities due to (131)I, yet significant suppression was achieved by NF-κB inhibition. Western blot proved (131)I could increase nuclear NF-κB concentration, while NF-κB inhibition reduced NF-κB concentration. Western blot also demonstrated significant up-regulation of XIAP, cIAP1, and Bcl-xL after (131)I therapy. And inhibition of NF-κB could significantly down-regulate these factors. Finally, synergism induced by combined therapy was displayed by significant enhancements of cleaved caspase 3 and PARP from Western blot, and of Annexin V positively staining from flow cytometry. The iodine uptake assay did not show significant changes when NF-κB was inhibited. CONCLUSION: We demonstrated that (131)I could induce NF-κB activation, which would attenuate (131)I efficacy in DTC cells. NF-κB inhibition by Bay 11-7082 or by p65 siRNA transfection was effective in suppressing NF-κB regulated anti-apoptotic changes and in combined regimen apoptosis was achieved synergistically.