Treatment and management of medullary thyroid microcarcinoma: a 10-year retrospective study from a single center.

OBJECTIVE: To explore individualized treatment and management methods for medullary thyroid microcarcinoma (MTMC). METHODS: Clinical data of patients with medullary thyroid carcinoma with a diameter ≤1 cm admitted to the First Affiliated Hospital of Kunming Medical University from June 2013 to June 20× were collected. Combined with different treatment guidelines for medullary thyroid carcinoma, factors affecting lymph node metastasis and postoperative disease status were analyzed. RESULTS: Twenty-nine patients with MTMC were included in the analysis, including 24 patients who underwent total thyroidectomy, 5 who underwent thyroid gland lobectomy, and 13 who experienced postoperative lymph node metastasis. Multifocal tumor and calcitonin (Ctn) were the influencing factors, while multifocal tumor, Ctn, lymph node metastasis, and AJCC stage affected the dynamic risk stratification of postoperative disease. CONCLUSION: Calcitonin detection is an important method for detecting MTMC. A tumor diameter ≤1 cm does not indicate that the tumor is in the early stage. The presence of multifocal tumors and Ctn should be used as important indicators for preoperative evaluation. Dynamic stratified risk assessment is critical in postoperative follow-up.

Transcriptome and metabolome sequencing identifies glutamate and LPAR1 as potential factors of anlotinib resistance in thyroid cancer.

OBJECTIVE: To explore the mechanism of anlotinib resistance in thyroid carcinoma. METHODS: We constructed an anlotinib-resistant thyroid carcinoma cell line and observed the effect of drug resistance on the functional activity of these cell lines. Transcriptome sequencing and metabolomic sequencing combined with biosynthesis analysis were used to explore and screen possible drug resistance regulatory pathways. RESULTS: Through transcriptomic sequencing analysis of drug-resistant cell lines, it was found that the differentially expressed genes of drug-resistant strains were enriched mainly in the interleukin 17, transforming growth factor-ß, calcium, peroxisome proliferator activated receptor, and other key signaling pathways. A total of 354 differentially expressed metabolic ions were screened using liquid chromatography-mass spectrometry/mass spectrometry to determine the number of metabolic ions in the drug-resistant strains. The results of the Venn diagram correlation analysis showed that glutamate is closely related to multiple pathways and may be an important regulatory factor of anlotinib resistance in thyroid carcinoma. In addition, eight common differentially expressed genes were screened by comparing the gene expression profiling interactive analysis database and sequencing results. Further quantitative real time polymerase chain reaction verification, combined with reports in the literature, showed that LPAR1 may be an important potential target. CONCLUSION: This is the first study in which the drug resistance of thyroid cancer to anlotinib was preliminarily discussed. We confirmed that anlotinib resistance in thyroid cancer promotes the progression of malignant biological behavior. We conclude that glutamate may be a potential factor for anlotinib resistance in thyroid cancer and that LPAR1 is also a potentially important target.

Trends of the prevalence rate of central lymph node metastasis and multifocality in patients with low-risk papillary thyroid carcinoma after delayed thyroid surgery.

Background: Active surveillance has been an option for patients with low-risk papillary thyroid carcinoma (PTC). However, whether delayed surgery leads to an increased risk of local tumor metastasis remain unclear. We sought to investigate the impact of observation time on central lymph node metastasis (CLNM) and multifocal disease in patients with low-risk PTC. Methods: Patients who were diagnosed with asymptomatic low-risk PTC, and with a pathological maximum tumor size ≤1.5 cm by were included. The patients were classified into observation group and immediate surgery group, and subgroup analyses were conducted by observation time period. The prevalence of CLNM, lymph node (LN) involved >5, multifocal PTC and bilateral multifocal PTC were considered as outcome variables. The changing trend and risk ratio of prevalence over observation time were evaluated by Mann-Kendall trend test and Logistics regression. Results: Overall, 3,427 and 1,860 patients were classified to the observation group and immediate surgery group, respectively. Trend tests showed that decreasing trends both on the prevalence of CLNM and LN involved >5 over the observation time, but the difference was not statistically significant, and the prevalence of multifocal PTC and bilateral multifocal PTC showed the significant decreasing trends. After adjustment, multivariate analysis showed no statistically significant difference between observed and immediate surgery groups in the four outcome variables. Conclusion: In patients with subclinical asymptomatic low-risk PTC, observation did not result in an increased incidence of local metastatic disease, nor did the increased surgery extent in patients with delayed surgery compared to immediate surgery. These findings can strengthen the confidence in the active surveillance management for both doctors and patients.

Single inferior parathyroid autotransplantation during total thyroidectomy with bilateral central lymph node dissection for papillary thyroid carcinoma: a retrospective cohort study.

BACKGROUND: Management of the inferior parathyroid gland using total thyroidectomy (TT) with central lymph node dissection (CLND) is still controversial. Therefore, we evaluated the safety and effectiveness of single inferior parathyroid autotransplantation. METHODS: The clinical data of patients with papillary thyroid carcinoma (PTC) who underwent TT with bilateral CLND from January 2018 to December 2020 were collected. Quality of life (QoL) was assessed using the Chinese version of the EORTC QLQ-C30 and THYCA-QOL. The patients were divided into an autotransplantation group and a preservation group according to whether a single inferior parathyroid gland was transplanted. The incidence of permanent hypoparathyroidism, the number of resected central lymph nodes (CLNs), the rate of recurrence reoperation, the rate of radioactive iodine (RAI) treatment, and the QoL score were compared between the two groups. RESULTS: A total of 296 patients were included in the study; there were 99 patients in the autotransplantation group and 197 in the preservation group. The incidence of permanent hypoparathyroidism was 3.0% (3/99) and 4.6% (9/197) in the autotransplantation and preservation groups, respectively (P = 0.532). The median number of resected CLNs was 12 (8-17) and 10 (6-14) in the autotransplantation and preservation groups, respectively (P = 0.015). No reoperations were performed for patients with CLN recurrence, and the rates of lateral lymph node (LLN) recurrence reoperation were 2.0% (2/99) and 3.6% (7/197) in the autotransplantation and preservation groups, respectively (P = 0.473). The RAI treatment rates were 12.1% (12/99) and 22.3% (44/197) in the autotransplantation and preservation groups, respectively (P = 0.034). A total of 276 questionnaires were recovered, including 84 in the autotransplantation group and 192 in the preservation group. The QoL of the two groups of patients is similar (P > 0.05). CONCLUSION: Single inferior parathyroid autotransplantation during thyroidectomy can be used to prevent permanent hypoparathyroidism and can enable more extensive CLND.

The impact of the initial operation of PTC in children on recurrence: 9-year experience in a single center.

PURPOSE: To summarize the treatment experience of single-center children with PTC and to explore the influence of initial surgery on the recurrence/metastasis of papillary thyroid carcinoma (PTC) in children. METHODS: A retrospective analysis of PTC case data of children (≤ 18 years old) who were admitted to and received surgical treatment in the First Affiliated Hospital of Kunming Medical University from January 2012 to December 2020. RESULTS: A total of 64 children with PTC were included, including 45 cases (70.31%) with a single lesion, and 19 cases (29.69%) with multiple lesions (≥ 2 lesions). Fifteen patients relapsed. Univariate analysis found that gender, thyroidectomy scope, central lymph node dissection, and lateral lymph node dissection were risk factors affecting reoperation; multi-factor analysis showed that central lymph node dissection was an independent risk factor affecting reoperation. According to Kaplan-Meier analysis, central lymph node dissection, total thyroidectomy (TT), lobectomy (LT), and disease-free survival (DFS) were statistically significant (p = 0.000, p = 0.000). CONCLUSION: At the time of diagnosis of PTC in children, the rate of lymph node metastasis in the central and lateral cervical regions is high. The vast majority of children with PTC should be treated with TT, and LT is chosen for a small number of patients. CND should be routinely lined.

Errate: Role of Ca²âº in Inhibiting Ischemia-Induced Apoptosis of Parathyroid Gland Cells in New Zealand White Rabbits.

In Figure 1A, the images of CG 24h group and Sham 72h group are duplicated, where the picture of Sham 72h group is correct, now the authors have corrected the picture of CG 24h group. In Figure 2A, the images of CG 72h and CSG 72h groups are duplicated, the images of CG 168h and CSG 168h groups are duplicated，where the pictures of CG 168h and CSG 72h groups are correct, now the authors have corrected the pictures of CG 72h and CSG 168h groups. In Figure 3B, the images of CG 24h group and CSG 72h group are duplicated, where the picture of CSG 72h group is correct, now the authors have corrected the picture of CG 24h group. Reference: Wei-han Cao, Yan-jun Su, Nian-qiu Liu, Ying Peng, Chang Diao, Ruo-chuan Cheng: Role of Ca²âº in Inhibiting Ischemia-Induced Apoptosis of Parathyroid Gland Cells in New Zealand White Rabbits. Med Sci Monit, 2020; 26: e920546. DOI: 10.12659/MSM.920546.

A Mathematical Model to Assess the Effect of Residual Positive Lymph Nodes on the Survival of Patients With Papillary Thyroid Microcarcinoma.

Background: Active surveillance (AS) has been considered the first-line management for patients with clinical low-risk papillary thyroid microcarcinoma (PTMC) who often have lymph node micrometastasis (m-LNM) when diagnosed. The "low-risk" and "high prevalence of m-LNM" paradox is a potential barrier to the acceptance of AS for thyroid cancer by both surgeons and patients. Methods: Patients diagnosed with PTMC who underwent thyroidectomy with at least one lymph node (LN) examined were identified from a tertiary center database (n = 5,399). A ß-binomial distribution was used to estimate the probability of missing nodal disease as a function of the number of LNs examined. Overall survival (OS) probabilities of groups with adequate and inadequate numbers of LNs examined were estimated using the Kaplan-Meier method in the Surveillance, Epidemiology, and End Results (SEER) database (n = 15,340). A multivariable model with restricted cubic splines was also used to verify the association of OS with the number of LNs examined. Results: The risk of residual m-LNM (missed nodal disease) ranged from 31.3% to 10.0% if the number of LNs examined ranged from 1 and 7 in patients with PTMC. With 7 LNs examined serving as the cutoff value, the intergroup comparison showed that residual positive LNs did not affect OS across all patients and patients aged ≥55 years (P = 0.72 and P = 0.112, respectively). After adjusting for patient and clinical characteristics, the multivariate model also showed a slight effect of the number of LNs examined on OS (P = 0.69). Conclusions: Even with the high prevalence, OS is not significantly compromised by persistent m-LNM in the body of patients with low-risk PTMC. These findings suggest that the concerns of LNM should not be viewed as an obstacle to developing AS for thyroid cancer. For patients with PTMC who undergo surgery, prophylactic central LN dissection does not provide a survival benefit.

Surgical treatment of pediatric and adolescent papillary thyroid cancer: a retrospective study of 54 patients in a single center

Abstract Objective: In 2015, American Thyroid Association (ATA) issued the first version of Management Guidelines for Children with Thyroid Nodules and Differentiated Thyroid Cancer. The purpose of this study is to evaluate whether the ATA pediatric guidelines recommended surgical approach for the patient can be applied to surgical treatment of pediatric PTC in China. Method: From April 2012 to December 2020, clinical data of children (≤18 years) with PTC consecutively admitted and treated with initial surgery in the study's department were retrospectively reviewed. Results: The authors found that the central lymph node metastasis (CLNM) rate was significantly higher than that in the lateral neck (83.33 % vs 62.96%, χ2 = 5.704, p = 0.017) .The lymph node metastasis rate was significantly lower in cN1b (-) patients than in cN1b (+) patient (55.00% vs 100.00%, χ2 = 15.263, p = 0.000); Meanwhile, the CLNM and LLNM rates of ipsilateral were significantly higher than those of contralateral central compartment (83.33༅vs 57.41༅%, χ2 = 8.704, p = 0.003). Lymph nodes of 51 lateral lymph node dissection (LND) were analyzed, which revealed the LNM rate of cN1b (-) patients was significantly lower than that of cN1b (+) patients (55.00% vs. 100.00%, χ2 = 15.263, p = 0.000). Conclusion: Children and adolescents have a higher rate of lymph node metastasis at the time of diagnosis. TT should be conducted in the majority of children with PTC. CND should be routinely performed; therapeutic LND is recommended for children with cN1b (+).

Surgical treatment of pediatric and adolescent papillary thyroid cancer: a retrospective study of 54 patients in a single center.

OBJECTIVE: In 2015, American Thyroid Association (ATA) issued the first version of Management Guidelines for Children with Thyroid Nodules and Differentiated Thyroid Cancer. The purpose of this study is to evaluate whether the ATA pediatric guidelines recommended surgical approach for the patient can be applied to surgical treatment of pediatric PTC in China. METHOD: From April 2012 to December 2020, clinical data of children (≤18 years) with PTC consecutively admitted and treated with initial surgery in the study's department were retrospectively reviewed. RESULTS: The authors found that the central lymph node metastasis (CLNM) rate was significantly higher than that in the lateral neck (83.33 % vs 62.96%, χ2 = 5.704, p = 0.017) .The lymph node metastasis rate was significantly lower in cN1b (-) patients than in cN1b (+) patient (55.00% vs 100.00%, χ2 = 15.263, p = 0.000); Meanwhile, the CLNM and LLNM rates of ipsilateral were significantly higher than those of contralateral central compartment (83.33༅vs 57.41༅%, χ2 = 8.704, p = 0.003). Lymph nodes of 51 lateral lymph node dissection (LND) were analyzed, which revealed the LNM rate of cN1b (-) patients was significantly lower than that of cN1b (+) patients (55.00% vs. 100.00%, χ2 = 15.263, p = 0.000). CONCLUSION: Children and adolescents have a higher rate of lymph node metastasis at the time of diagnosis. TT should be conducted in the majority of children with PTC. CND should be routinely performed; therapeutic LND is recommended for children with cN1b (+).

Case Report: Anlotinib Therapy in a Patient With Recurrent and Metastatic RAIR-DTC Harboring Coexistent TERT Promoter and BRAFV600E Mutations.

We describe a case of recurrent and metastatic radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC) treated with anlotinib in this report. The patient was randomized to placebo initially, after disease progressed at C8 (C is the treatment cycle), the patient was referred to the open label therapy of anlotinib, 12 mg p.o. daily with a 2-week on/1-week off regimen. Partial response was achieved at C2 with anlotinib treatment. To date, over 37 months of progression-free survival (PFS) has been achieved. Adverse effects were tolerable and manageable in this patient. Molecular characterization revealed coexistent C228T mutation of TERT promoter and BRAFV600E mutations. Favorable clinical outcome in this patient suggests that anlotinib might provide a novel effective therapeutic option for patients with RAIR-DTC. TERT and BRAFV600E mutations may represent as biomarker for predicting salutary effects of anlotinib.

The role of P62 in the development of human thyroid cancer and its possible mechanism.

BACKGROUND: Thyroid cancer is the most common malignancy in human endocrine system. Increasing evidence has indicated that p62 plays a key role in tumorigenesis. The roles and underlying molecular mechanisms of P62 in thyroid cancer, however, remain to be elucidated. METHODS: The expression levels of P62 in thyroid tumor tissues and thyroid cancer cells were detected by western blotting and qRT-PCR. Then, the effects of up-regulation or down-regulation of P62 on thyroid cancer cell proliferation, migration, invasion, cell cycle and apoptosis were measured by CCK-8 assay, transwell assay, flow cytometry and transwell assay, respectively. In terms of the mechanism, P62 could stimulate thyroid cancer progression by the activation of nuclear factor-kappa B (NF-κB) signaling pathway. RESULTS: P62 was highly expressed in thyroid tumor tissues. Furthermore, high expression of p62 was observed in PTC cell lines, and especially in the K1 and TPC-1 cells. In vitro, the up-regulation of p62 promoted cell proliferation, migration, and invasion of thyroid cancer cells, whereas the knockdown of p62 resulted in the opposite effect. Knock-down of P62 increased the number of cells in the G0/G1 phase but reduced it in the S and G2/M phase. Moreover, we confirmed that overexpression of p62 inactivated NF-κB pathway with sequencing analysis and bioinformatics analysis. CONCLUSION: This research work suggested that p62 could promote PTC cell proliferation, migration, and invasion via NF-κB signaling pathway. Furthermore, p62 is a potential biomarker which might be closely related to the tumorigenesis in PTC. Its potential role as a therapeutic target for PTC is worthy of further study.

Risk probability model for residual metastatic lymph node in patients with papillary thyroid microcarcinoma undergoing cervical central lymph node dissection.

To establish a risk probability model for residual metastatic lymph nodes in patients with papillary thyroid microcarcinoma (PTMC) after cervical central lymph node dissection (CLND). The clinical data of patients with PTMC treated in the First Affiliated Hospital of Kunming Medical University from 2007 to 2020 were retrospectively reviewed. All patients underwent thyroidectomy with CLND, and at least one lymph node was examined. Based on the distribution characteristics of metastatic lymph nodes from this retrospective cohort, a probabilistic model for the risk of residual metastatic lymph node was established. ß-Binomial distribution was used to estimate the probability of residual metastatic lymph node as a function of the number of lymph nodes examined. Among 5399 patients included in the probabilistic model, central lymph node metastases were observed in 1664 cases (30.8%). After model correction, the real lymph node metastasis rate increased from 30.8% to 38.9%. The probability of false negative of central lymph node was estimated to be 31.3% for patients with a single node examined, while decreased to 10.0% and 4.9% when 7 and 12 nodes were examined, respectively. In the sensitivity analysis limited to patients with or without Hashimoto thyroiditis, the performance of probability model was also satisfactory. The established risk probability model in this study quantifies the risk of residual metastatic lymph nodes after CLND in patients with PTMC, which can be used as complementary indicators for the risk of recurrence/persistence disease at postoperative evaluation. The study also provides a new method to evaluate the impact of residual metastatic lymph nodes on the prognosis of tumor patients through retrospective data.

The Potential Action of Thomsen-Friedenreich Monoclonal Antibody (A78-G/A7) in Thyroid Cancer.

BACKGROUND: Thomsen-Friedenreich antibody (TF-Ab) is a specific antibody against the Thomsen-Friedenreich antigen (TF-Ag). At present, studies on a number of other tumors have shown that TF-Ab can effectively inhibit metastasis and induce apoptosis in tumor cells. However, the role of TF-Ab in thyroid cancer (TC) remains unclear. MATERIALS AND METHODS: Normal subjects and patients with primary papillary TC with or without lymph node metastasis were tested for TF-Ab expression by enzyme-linked immunosorbent assays (ELISAs). Immunofluorescence was used to assess the expression of TF-Ag in thyroid papillary carcinoma with or without lymph node metastasis and undifferentiated cancer tissues. To evaluate the role of TF-Ab in TC, the effects of TF monoclonal antibody (mAb A78-G/A7) on cell biological function were investigated by MTT assays, flow cytometry, adhesion assays and transwell experiments. RESULTS: Compared with normal individuals, TF-Ab levels in patients with TC were decreased, but no changes were observed with respect to lymph node metastasis. The expression of TF-Ag in TC tissues was relatively higher than that detected in adjacent tissues, but it was not affected by the presence or absence of lymph node metastasis. Upon treatment mAb A78-G/A7 treating, TC cell cycles were affected, meanwhile the abilities to adhere, invade and migrate were also significantly reduced. CONCLUSION: The results of the present study showed that mAb A78-G/A7 could affect the invasion and migration of all assayed TC cell lines. The effects of mAb A78-G/A7 on the cell cycle, adhesion, invasion and migration of TC cells were more significant than those observed for proliferation and apoptosis.

Blocking OLFM4/HIF-1α axis alleviates hypoxia-induced invasion, epithelial-mesenchymal transition, and chemotherapy resistance in non-small-cell lung cancer.

Hypoxia is a common biological hallmark of solid cancers, which has been proposed to be associated with oncogenesis and chemotherapy resistance. The purpose of the present study was to investigate the role and underlying mechanisms of olfactomedin 4 (OLFM4) in the hypoxia-induced invasion, epithelial-mesenchymal transition (EMT), and chemotherapy resistance of non-small-cell lung cancer (NSCLC). We observed dramatically upregulated expression of OLFM4 in several NSCLC cell lines, and this effect was more pronounced in A549 and H1299 cells. In addition, our data revealed that OLFM4 expression was remarkably increased in both A549 and H1299 cells under hypoxic microenvironment, accompanied by enhanced levels of hypoxia-inducible factor (HIF)-1α protein. The HIF-1α level was elevated in response to hypoxia, resulting in the regulation of OLFM4. Interestingly, OLFM4 was a positive regulator of hypoxia-driven HIF-1α production. Moreover, depletion of OLFM4 modulated multiple EMT-associated proteins, as evidenced by the enhanced E-cadherin levels along with the diminished expression of N-cadherin and vimentin in response to hypoxia, and thus blocked invasion ability of A549 and H1299 cells following exposure to hypoxia. Furthermore, ablation of OLFM4 accelerated the sensitivity of A549 cells to cisplatin under hypoxic conditions, implying that OLFM4 serves as a key regulator in chemotherapeutic resistance under hypoxia. In conclusion, OLFM4/HIF-1α axis might be a potential therapeutic strategy for NSCLC.

Establishment and validation of the scoring system for preoperative prediction of central lymph node metastasis in papillary thyroid carcinoma.

Early preoperative diagnosis of central lymph node metastasis (CNM) is crucial to improve survival rates among patients with papillary thyroid carcinoma (PTC). Here, we analyzed clinical data from 2862 PTC patients and developed a scoring system using multivariable logistic regression and testified by the validation group. The predictive diagnostic effectiveness of the scoring system was evaluated based on consistency, discrimination ability, and accuracy. The scoring system considered seven variables: gender, age, tumor size, microcalcification, resistance index >0.7, multiple nodular lesions, and extrathyroid extension. The area under the receiver operating characteristic curve (AUC) was 0.742, indicating a good discrimination. Using 5 points as a diagnostic threshold, the validation results for validation group had an AUC of 0.758, indicating good discrimination and consistency in the scoring system. The sensitivity of this predictive model for preoperative diagnosis of CNM was 4 times higher than a direct ultrasound diagnosis. These data indicate that the CNM prediction model would improve preoperative diagnostic sensitivity for CNM in patients with papillary thyroid carcinoma.

miR-181a-5p is downregulated and inhibits proliferation and the cell cycle in prostate cancer.

Prostate cancer (PCa) is one of the most common cancers in men worldwide. However, the detailed molecular mechanisms underlying PCa tumorigenesis and progression remain largely unclear. MicroRNAs are key regulators of gene post-transcriptional expression in human cancer. In this study, we used public datasets, including GSE21036, GSE14857 and GSE45604 to analyze the expression of miR-181a in PCa. We also explored the potential role of miR-181a by using bioinformatics analysis and gain of function assay. miR-181a was down-regulated in PCa. Bioinformatics analysis revealed miR-181a was significantly involved in regulating cell metabolic process and gene expression. Of note, gain of function assay results showed overexpression of miR-181a could significantly inhibit cell proliferation by inducing G1 cell cycle arrest. Our results suggest miR-181a-5p may be adiagnostic and therapeutic biomarker for prostate cancer.

Risk factors of central lymph node metastasis of papillary thyroid carcinoma: A single-center retrospective analysis of 3273 cases.

Due to the lack of an accurate preoperative diagnostic method of central lymph node metastasis (CLNM) of papillary thyroid cancer (PTC), the prophylaxis of central lymph node dissection remains controversial. The present study investigated the clinicopathological features of PTC patients and the risk factors of CLNM. The clinicopathological features of PTC patients with respect to sex, age, initial symptoms, observation, tumor diameter, multifocality, extrathyroidal invasion, and pathological data combined with other thyroid diseases, were analyzed retrospectively. The risk factors of CLNM were analyzed by Chi-squared test and multivariate logistic regression model. The CLNM rate of PTC was 40.6% (1331/3273). On average, 7.0 (4.0, 12.0) central lymph nodes were dissected, and 3.70 (±3.8) lymph nodes were proved to be metastatic. Univariate analysis showed that sex (P < .001), age (P < .001), tumor diameter (P < .001), extrathyroid invasion (P < .001), multifocality (P = .001), concurrent nodular goiter (P < .001), initial symptoms (P < .001), and observation or not (P < .001) were related to CLNM. The observation time was neither related to CLNM (P = .469) nor extrathyroidal invasion (P = .137). Tumors localized in the lower part of the thyroid were the risk factors for CLNM (P < .001) while multifocality was unrelated (P = .68). The metastasis rate of bilateral multiple regions > unilateral multiple regions > single region (P = .003). Multivariate logistic regression analysis showed that sex, age, tumor diameter, extrathyroidal invasion, and observation were independent risk factors of CLNM. Male, younger age, large tumor size, and extrathyroidal invasion were independent risk factors for CLNM. CLNM was related to multiple regions occupied by tumors in the thyroid but unrelated to multifocality. The tumor occupying a single region and localized in the lower part of thyroid could be used as a predictive factor for CLNM. For tumors that could not be diagnosed as benign or malignant, observation may be an option, since no evidence of disease progression was presented during observation.

Interferon-α2b gene-modified human bone marrow mesenchymal stem cells inhibit hepatocellular carcinoma by reducing the Notch1 levels.

AIMS: Hepatocellular carcinoma (HCC) is the most common liver cancer worldwide. IFN-α has been used in clinics as a potential therapeutic strategy to treat HCC. In spite of the therapeutic effects, IFN-α caused many side effects due to its short half-life and high dose. Here, we aim to detect the anti-tumor effect of a novel gene delivery system - IFN-α2b gene-modified human bone marrow mesenchymal stem cells (BMSCs) in HCC. MAIN METHODS: Two HCC cell lines, HepG2 and Huh7 were used in the current study. The secretion of IFN-α2b in the BMSC cultured conditioned media (CM) was measured by ELISA. The cell cycle was determined by flow cytometry. The Xenografted NOD/SCID mouse tumor model was generated by subcutaneous inoculation with HepG2 cells. KEY FINDINGS: We found that the IFN-α2b-modified BMSC (BMSC/IFN-α2b) could express IFN-α2b stably. The CM from BMSC/IFN-α2b inhibited the proliferation of HCC cells with a much lower growth rate compared with BMSC/vector-CM or DMEM culture group. We further demonstrated that the population of G2/M phase was higher in BMSC/IFN-α2b-CM treated cells than the other two groups. In addition, BMSC/IFN-α2b could significantly inhibit tumor growth in NOD/SCID mice. Moreover, we found that BMSC/IFN-α2b-CM could significantly decrease the mRNA and protein levels of Notch signaling molecules of HCC in vitro and in vivo. SIGNIFICANCE: Our data demonstrated that BMSC/IFN-α2b could significantly inhibit HCC cell growth through negatively regulating the Notch signaling, which suggested that IFN-α2b-modified BMSC may be used as an effective therapeutic strategy for hepatomas.

Expression of MUC1 and CD176 (Thomsen-Friedenreich antigen) in papillary thyroid carcinomas.

The incidence of thyroid cancer has appeared as an increasing trend globally, especially in Asian countries. In this study, the expression of mucin-1 (MUC1) and Thomsen-Friedenreich antigen, Galß1-3GalNAcα1-R (CD176) was investigated by immunohistochemistry in papillary thyroid carcinomas (PTCs), which accounts for approximately 80 % of all thyroid cancer. We found that 78 % of PTC overexpressed MUC1. Importantly, we observed firstly that CD176 was expressed in 63 % of PTC, but was faintly or not expressed in normal thyroid tissues and benign thyroid disease tissues, indicating that CD176 is also a tumour-associated antigen for PTCs. Moreover, expression of CD176 was strongly correlated with MUC1 by immunohistochemical staining in PTCs. Furthermore, we used the immunochemical method to confirm that MUC1 is a common and main carrier of CD176 in PTCs. Our data demonstrated that MUC1 and CD176 might be promising biomarkers for thyroid cancer.