Treatment Of Papillary Thyroid Carcinoma Research Articles

Radioguided sentinel lymph node biopsy in patients with papillary thyroid carcinoma.

The ATA guidelines do not recommend prophylactic central compartment neck dissection in patients with T1-T2 papillary thyroid carcinoma (PTC) with no clinical evidence of lymph node metastasis, however patients' staging is recommended. Lymph node metastasis may be present also in small PTC, but preoperative ultrasound identifies suspicious cervical lymphadenopathy in 20-30% of patients. The role of sentinel lymph node biopsy (SLNB) remain open to debate. It has been shown that the identification rate of SLN in PTC patients is improved using a radiotracer compared to a dye technique. The aim of this systematic review was to evaluate the role of radioguided SLNB (rSLNB) in the treatment of PTC patients. A systematic search was performed in the PubMed and Embase database to identify all original articles regarding the application of rSLNB in PTC patients. The primary outcome was false negative rate (FNR) of the rSLNB; the secondary outcomes were SLN intraoperative identification rate (IIR), site of lymph node metastasis, and persistent disease during follow up. Twelve studies were included. Most of PTC patients were T1-T2. The overall SLN IIR, SLN metastatic rate, and FNR were 92.1%, 33.6%, and 25.4%, respectively. Overall, lymph node metastasis were found in the central compartment (23.0%) and in the lateral compartments (10.6%). The persistent disease in patients who underwent SLNB associated to lymph node dissection (LND) in the same compartment of the SLN regardless of the SLN status was 0.6%. In all PTC patients, also in T1-T2 stage, due to the high FNR the SLNB performed alone should be abandoned and converted into a technique to guide the lymphadenectomy in a specific neck compartment (i.e., central or lateral) based on the radioactivity, regardless of the SLN status, for better lymph node staging and selection of patients for postoperative radioiodine ablation.

Cervical Lymph Node Metastases After Thyroidectomy for Papillary Thyroid Carcinoma Usually Remain Stable for Years.

Lymph node (LN) recurrence detected by ultrasound (US) is a very common problem after initial treatment for papillary thyroid carcinoma (PTC). Most patients with PTC have an excellent disease-specific survival even with LN recurrence. Recently, watchful waiting with serial cervical US evaluations would be considered a reasonable approach to management of LN recurrence in selected patients. On the other hand, some patients with LN recurrence have demonstrated clinically significant disease progression during follow-up. The objective of the present study was to document the changes of cervical LN metastases after initial treatment and identify useful information for deciding how best to manage individual patients with LN recurrence. This retrospective review identified 83 consecutive PTC patients with at least one LN on the postoperative US diagnosed with fine needle aspiration biopsy or the thyroglobulin titer in the wash-out of the needle. The change in LN size was determined using serial US studies over time. The subjects were 15 men and 68 women, with a median age at initial surgery of 50.6 years (range, 18-80 years). The median LN size at the start of the observation period was 1.3 cm (range, 0.5-2.4 cm) in the largest diameter. After a median follow-up of 7.2 years, the median growth rate of the nodes showing structural progression was 1.4 mm per year (range, 0-12.0 mm/year). Seventeen of 83 patients (20.5%) demonstrated an increase in LN size of at least 3 mm, only 8.4% (7 of 83) had an increase of at least 5 mm, and 39.7% (33 of 83) resolved. Distant metastases were present in 11 of 83 patients. Ten-year and fifteen-year disease-specific survival rates after diagnosis of LN recurrence were 84.7% and 72.6%, respectively. Older age and recurrent LN growth of more than 3 mm/year were recognized as independent predictors for short survival on both univariate and multivariate analyses (p < 0.05). Most lymph node recurrences may remain stable for a long time and not be immediately life-threatening. However, recurrent LN growth of more than 3 mm per year could be related to mortality.

A nomogram predicting contralateral central neck lymph node metastasis for papillary thyroid carcinoma.

Central compartment neck dissection (CCND) is recommended for patients with papillary thyroid carcinoma (PTC). However, whether to perform contralateral CCND remains unclear. An individualized estimation of the contralateral central neck metastasis (CNM) risk would assist in the tailoring of treatment for PTC patients. Consecutive patients who underwent bilateral CCND for unilateral PTC between 2012 and 2014 in a tertiary center were identified. The clinicopathological data of 142 patients were analyzed retrospectively. The variables that had clinical significance in the final multivariate logistic regression model were built into a nomogram to assess the risk of metastasis of the contralateral central compartment. This model was internally validated using bootstrap resampling. This nomogram demonstrated good calibration and discrimination, with a concordance index of 0.834 (bootstrap corrected, 0.824). The variables with the greatest influence on the risk of contralateral CNM in this model included tumor size, the number of positive lymph nodes, and extranodal extension in the ipsilateral central neck. This nomogram integrates three variables to estimate an individualized risk of contralateral CNM in unilateral PTC patients. This model may assist in individual decision-making regarding contralateral CCND and help avoid the over- and under-treatment of PTC. J. Surg. Oncol. 2016;114:703-707. © 2016 Wiley Periodicals, Inc.

Percutaneous laser ablation for treatment of locally recurrent papillary thyroid carcinoma

To evaluate the efficacy and safety of ultrasound-guided percutaneous laser ablation (PLA) for recurrent papillary thyroid carcinomas (PTC) <15 mm in the neck. A retrospective study was conducted in 21 patients with 27 recurrent PTC lesions who underwent PLA. The extent of ablation was assessed by contrast-enhanced ultrasonography (CEUS) after PLA. Measurement of the volume of tumour and serum thyroglobulin, and clinical evaluation were performed at 7 days, and 1, 3, 6, and 12 months, and every 6 months thereafter. The procedure was well tolerated. Of 21 patients, 18 were successfully treated in a single session. Incomplete ablation was detected by CEUS in three patients, and a second ablation was performed. The mean largest diameter and the average baseline volume were reduced from 7.5±2.8mm and 105.4±114mm3 to 0.4±1mm and 0.8±2.4mm3 at the final follow-up. Ultrasound-guided PLA is effective for the treatment of recurrent PTCs with a comparable success rate to radio-iodine therapy, and it may become a primary choice of treatment for recurrent PTCs in selected patients who are ineligible for surgery and/or prefer not to have further surgery.

Evaluation and Management of Chemotherapy-Induced Epiphora, Punctal and Canalicular Stenosis, and Nasolacrimal Duct Obstruction.

To describe the frequency, mechanisms, and treatment of epiphora caused by chemotherapeutic agents. Review of relevant articles published in PubMed. The chemotherapeutic drugs best documented to cause epiphora are 5-fluorouracil and docetaxel; with both of these drugs, the main mechanism underlying epiphora is canalicular stenosis. Drugs less commonly reported to cause epiphora include S-1, capecitabine, imatinib, topical mitomycin C, and radioactive iodine for treatment of papillary thyroid carcinoma. While all the above-mentioned drugs can be associated with epiphora, some drugs and administration schedules cause only punctal and canalicular inflammation, whereas others cause significant canalicular stenosis. For example, weekly administration of docetaxel is far more likely to cause canalicular stenosis than every-3-weeks administration. The literature suggests that, in patients who receive weekly docetaxel, silicone stenting at the first sign of recurrent or progressive canalicular stenosis can prevent severe irreversible canalicular stenosis and avoid the need for a conjunctivodacryocystorhinostomy. S-1 and radioactive iodine have been reported to cause nasolacrimal duct obstruction. Early recognition of punctal and canalicular stenosis or nasolacrimal duct blockage and early intervention with topical steroids and canalicular stenting in patients at risk for permanent canalicular scarring are important to avoid the need for more invasive and complicated procedures. A variety of chemotherapeutic agents have been reported to cause epiphora, and some of these drugs have also been documented to cause obstructions of the lacrimal drainage system. Early recognition and management of epiphora is important and leads to better outcomes.

MiR-449 overexpression inhibits papillary thyroid carcinoma cell growth by targeting RET kinase-β-catenin signaling pathway.

Papillary thyroid carcinoma (PTC) is the most common thyroid cancer and represent approximately 80% of all thyroid cancers. The present study is aimed to investigate the role of microRNA (miR)-449 in the progression of PTC. Our results revealed that miR-449 was underexpressed in the collected PTC specimens compared with non-cancerous PTC tissues. Overexpression of miR-449 induced a cell cycle arrest at G0/G1 phase and inhibited PTC cell growth invitro. Further studies revealed that RET proto-oncogene (RET) is a novel miR-449 target, due to miR-449 bound directly to its 3'-untranslated region and miR-449 mimic reduced the protein expression of RET. Similar to the effects of miR-449 overexpression, RET downregulation inhibited cell growth, whereas RET overexpression reversed the inhibitive effect of miR-449 mimic. Furthermore, miR-449 overexpression inhibited the nuclear translocation of β-catenin and reduced the expression of several downstream genes, including c-Myc, cyclinD1, T cell-specific transcription factor (TCF) and lymphoid enhancer-binding factor 1 (LEF-1), and inactivated the β-catenin pathway in TPC-1 cells. Moreover, overexpression of β-catenin prevented miR-449-reduced cell cycle arrest and cell viability. In xenograft animal experiments, miR-449 overexpression effectively suppressed the tumor growth of PTC. Taken together, our research indicated that miR-449 functions as an anti-oncogene by targeting RET, and that miR-449 overexpression inhibited the growth of PTC by inactivating the β-catenin pathway. Thus, miR-449 may serve as a potential therapeutic strategy for the treatment of PTC.

ZNRF3 is downregulated in papillary thyroid carcinoma and suppresses the proliferation and invasion of papillary thyroid cancer cells.

Zinc and ring finger 3 (ZNRF3) is a transmembrane E3 ubiquitin ligase that has emerged as an important regulator of cancer development; however, its cancer-related function remains controversial. Here, we investigated the possible role of ZNRF3 in thyroid carcinoma (TC). We found that ZNRF3 is downregulated in papillary thyroid carcinoma (PTC) compared to normal thyroid tissues and inversely correlated with the degree of cell differentiation. Overexpression of ZNRF3 significantly suppressed cell malignant behaviors, including cell proliferation, migration, and invasion in vitro, as well as tumor growth in vivo. Consistent with recent studies showing that ZNRF3 is involved in the Wnt/β-catenin pathway, ZNRF3 overexpression negatively regulated β-catenin activation, modulating PTC cell behaviors. Clinical specimens revealed a significant inverse correlation between ZNRF3 and β-catenin mRNA levels. Taken together, these results provide insight into a potential tumor suppressor role of ZNRF3 in PTC progression, and may have potential clinical relevance for the prognosis and treatment of PTC.

Abstract 3117: Pleiotrophin is a marker of poor prognosis in Middle Eastern papillary thyroid carcinoma

Abstract Pleiotrophin (PTN) is a heparin binding growth factor known to have role in neuronal development. It is highly expressed in embryo but has a very limited expression in adult tissues. PTN is considered a proto-oncogene and has been hypothesized to play role in oncogenesis as its expression is found to be increased in many different cancer subtypes. Its role in cell transformation, cell growth, survival, migration and angiogenesis has also been shown in various different types of cancers. The function of PTN is hypothesized to be carried out by its interaction with cell surface proteoglycans or binding to its selective cell surface receptor, protein tyrosine phosphatase receptor Z1 (PTPRZ1). The significance of role of PTN in pathogenesis of thyroid cancer has not been explored especially with the fact that papillary thyroid carcinoma (PTC) originating in this ethnic population is the second most common female malignancy, after breast. So in search for novel druggable molecular target we sought for PTN expression in a large cohort of Saudi PTC. We analysed PTN alteration in more than 1000 primary papillary thyroid carcinoma in a tissue microarray format with clinical follow up data. We found that PTN was overexpressed in 65.5% (658/1006) of PTC and was significantly associated with aggressive clinical parameters such as tall cell variant histological subtype (p = 0.0333), extrathyroidal extension (p = 0.0292), lymphovascular invasion (p = 0.0182) and large tumour size (p = 0.0160). Important significant molecular association was seen with PTPRZ-1 (p = 0.0316), Midkine (p = 0.0008) and pSTAT-3 (p&amp;lt;0.0001). Finally patients showing PTN overexpression have worse disease free survival compared to patients showing low or absent PTN expression (p = 0.0218). On multivariate analysis PTN is found to be an independent marker of poor prognosis taking into consideration parameters such as Age, Stage, Lymph node status and Extrathyroidal extension (p = 0.0430). This study highlights the importance of PTN as druggable molecular target which can be therapeutically exploited by its inhibitors in treatment of PTC. Keywords: Papillary Thyroid Cancer; Pleiotrophin; Pleiotrophin Receptor Citation Format: Shaham Beg, Maqbool Ahmed, Azhar Hussein, Rong Bu, Zeeshan Qadri, Saif AlSobhi, Fouad Al Dayel, Abdul K. Siraj, Khawla S. Al-Kuraya. Pleiotrophin is a marker of poor prognosis in Middle Eastern papillary thyroid carcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3117.

COMPLICATION OF TOTAL THYROIDECTOMY PLUS LYMPH NODE GROUP VI DISSECTION IN PAPILLARY THYROID CARCINOMA PATIENTS

Background: Although lymph-node metastases are common in papillary thyroid cancer, there is considerable debate concerning the use of routine prophylactic lymph-node group VI dissection for all patients undergoing total thyroidectomy. This study was identification the complications and the rate of recurrence of total thyroidectomy plus lymph node group VI dissection in papillary thyroid carcinoma patients. Materials and methods: A prospective study was conducted on 60 patients with papillary thyroid carcinoma. They underwent total thyroidectomy with or without lymph node group VI dissection. Evaluation of postoperative complications and early recurrence rate /distant metastasis after 2 years. Results: The incident of transient hypoparathyroidism in the grouptotal thyroidectomy with or without lymph node group VI dissection respectively 13.3% and 6.7%. Neck lymph node dissection group VI helps detect 40.9% of cases of metastatic lymph nodes clinically undetectable. Neck lymph node recurrence rate in patients with lymph node group VI dissection is lower than group without dissection (3.3% versus 23.3%). Conclusions: Lymph nodes group VIdissection in preventive treatment of papillary thyroid carcinoma should be done. Key words: PTC, lymph-node group VI dissection

The Role of miRNA in Papillary Thyroid Cancer in the Context of miRNA Let-7 Family

Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy. RET/PTC rearrangement is the most common genetic modification identified in this category of cancer, increasing proliferation and dedifferentiation by the activation of the RET/PTC-RAS-BRAF-MAPK-ERK signaling pathway. Recently, let-7 miRNA was found to reduce RAS levels, acting as a tumor suppressor gene. Circulating miRNA profiles of the let-7 family may be used as novel noninvasive diagnostic, prognostic, treatment and surveillance markers for PTC.

Long noncoding RNA are aberrantly expressed in human papillary thyroid carcinoma.

Long noncoding RNAs (lncRNAs) have emerged as key regulatory molecules at almost every level of gene expression regulation. The altered expression of lncRNAs is a characteristic of numerous types of cancer, and lncRNAs have been demonstrated to promote the development, invasion and metastasis of tumors through various mechanisms. However, the role of lncRNAs in papillary thyroid carcinoma (PTC) remain unclear. In the present study, differentially expressed lncRNAs and mRNAs were detected by human lncRNA microarray in three pairs of PTC and adjacent noncancerous samples. The microarray results revealed that 675 lncRNAs and 751 mRNAs were abnormally expressed in the three PTC samples compared with adjacent noncancerous samples (fold change ≥2.0; P<0.05). To validate the microarray results, 8 differentially expressed lncRNAs were randomly selected for quantitative polymerase chain reaction (qPCR). The results of qPCR were consistent with the microarray data; the 8 lncRNAs had an aberrant expression in the PTC samples compared with the adjacent noncancerous samples. Gene ontology and pathway analysis indicated that there were 7 downregulated pathways and 29 upregulated pathways in PTC. LncRNA classification and subgroup analysis revealed 7 pairs of enhancer-like lncRNA-mRNA, 9 pairs of antisense lncRNA-mRNA and 45 pairs of lncRNA-mRNA were differentially expressed between PTC and their paired noncancerous samples. In conclusion, the present study identified a series of novel PTC-associated lncRNAs. Further study with these lncRNAs is instrumental for the identification of novel target molecules that could lead to improved diagnosis and treatment for PTC.

Key genes and pathways predicted in papillary thyroid carcinoma based on bioinformatics analysis.

The aim of this study was to predict the key genes and pathways associated with papillary thyroid carcinoma (PTC). Based on the microarray data of GSE3467 from Gene Expression Omnibus database, we identified the differentially expressed genes (DEGs) between 9 PTC samples and 9 normal controls. With the identified DEGs, functional enrichment analyses were performed. Additionally, a protein-protein interaction network was constructed to screened out some key gene nodes. These key nodes were then performed clustering analysis and pathway enrichment analysis. Furthermore, human PTC-associated network was constructed based on these key genes to investigate the potential relationships between genes and PTC. A total of 651 up-regulated and 692 down-regulated DEGs were identified in PTC samples compared with controls. The up-regulated DEGs, such as complement component 3 (C3), were mainly enriched in hsa04610:Complement and coagulation cascades. The down-regulated DEGs, including paired box 8 (PAX8), peroxisome proliferator-activated receptor gamma (PPARG), and cadherin 1, type 1 were found enriched in hsa05216:Thyroid cancer. Total 33 DEGs were considered as key genes, such as PAX8, PPARG and Jun proto-oncogene (JUN). Disease-associated network analysis found that 15 key genes such as JUN, PPARG and matrix metallopeptidase 9 (MMP9) were involved in this network. DEGs of C3, PPARG, PAX8, JUN and MMP9 were differentially expressed in PTC samples and may be used as potential biomarkers in the diagnosis and treatment of PTC. Additionally, pathways of complement and coagulation cascades and thyroid cancer may also play important roles in the development of PTC.

Hypermethylation of HIC1 and aberrant expression of HIC1/SIRT1 contribute to papillary thyroid carcinoma

Objective To explore promoter methylation of HIC1 gene and the expression of HIC1/SIRT1 related to the occurrence, development, and metastasis of papillary thyroid carcinoma. Methods Using Bisulfite sequencing PCR to analyze the promoter methylation of HIC1 gene. Using quantitative real-time PCR and Western blot to analyze expression differences of HIC1 and SIRT1 genes in tissues of papillary thyroid carcinoma(40 cases) and in adjacent normal thyroid(40 cases), of which datas were analyzed by statistics. Results The degree of HIC1 gene promoter methylation was significantly higher than that in adjacent normal tissues(P<0.01). The degree of HIC1 gene promoter methylation in papillary thyroid carcinoma was related to lymph node metastasis, age, and the tumor-node-metastasis stages(P<0.01). Compared with the expression of HIC1 mRNA and protein in adjacent normal thyroid tissue, that in papillary thyroid carcinoma was significantly lower(P<0.01), while the expression of SIRT1 mRNA and protein in papillary thyroid carcinoma was significantly higher(P<0.01). The lower expression of HIC1 mRNA and protein in the tumor tissues was related to the stage of lymph node metastasis, age, and the tumor-node-metastasis stages(P<0.05). There was a strong negative correlation between the degree of HIC1 gene promoter methylation and expression of HIC1 in papillary thyroid carcinoma(P<0.05). The expression of HIC1 mRNA and protein between that of SIRT1 also showed a strong negative correlation(P<0.01). Conclusion Promoter hypermethylation of HIC1 and aberrant expression of HIC1/SIRT1 in papillary thyroid carcinoma may play a significant role in the oncogenesis and progress of papillary thyroid carcinoma. HIC1 is expected to become a new marker for prevention and treatment of papillary thyroid carcinoma. (Chin J Endocrinol Metab, 2016, 32: 386-390) Key words: Hypermethylated in cancer 1; Silent mating type information regulation 2 homolog 1; Papillary thyroid carcinoma; Methylation

Inter-Observer Variation in the Pathologic Identification of Minimal Extrathyroidal Extension in Papillary Thyroid Carcinoma.

Extrathyroidal extension (ETE) is a significant prognostic factor in papillary thyroid carcinoma (PTC). Minimal extrathyroidal extension (mETE) is characterized by involvement of the sternothyroid muscle or perithyroid soft tissue, and is generally identified by light microscope examination. Patients with mETE, identified pathologically, are automatically upstaged to pT3. However, the prognostic implications of mETE have been a source of controversy in the literature. Moreover, there is also controversy surrounding the identification of mETE on pathological specimens. The objective of this study was to determine the level of agreement among expert pathologists in the identification of mETE in PTC cases. Eleven expert pathologists from the United States, Italy, and Canada were asked to perform a review of 69 scanned slides of representative permanent sections of PTC specimens. Each slide was evaluated for the presence of mETE. The pathologists were also asked to list the criteria they use to identify mETE. The overall strength of agreement for identifying mETE was slight (κ = 0.14). Inter-pathologist agreement was best for perithyroidal skeletal muscle involvement (κ = 0.46, moderate agreement) and worst for invasion around thick-walled vascular structures (κ = 0.02, slight agreement). In addition, there was disagreement over the constellation of histologic features that are diagnostic for mETE, which affected overall agreement for diagnosing mETE. Overall agreement for the identification of mETE is poor. Disagreement is a result of both variation in individual pathologists' interpretations of specimens and disagreement on the histologic criteria for mETE. Thus, the utility of mETE in staging and treatment of PTC is brought into question. The lack of concordance may explain the apparent lack of agreement regarding the prognostic significance of this pathologic feature.

MiR-486-5p inhibits cell growth of papillary thyroid carcinoma by targeting fibrillin-1.

Previous studies have demonstrated that miR-486-5p functions as a tumor suppressor or oncogene in various types of cancer. In the present study, we showed that miR-486-5p was significantly down-regulated in papillary thyroid carcinoma (PTC) tissues and cell lines, whereas miR-486-5p down-regulation inhibited PTC cell proliferation and increased apoptosis. Conversely, under-expression of miR-486-5p enhanced PTC cell proliferation and decreased apoptosis. Fibrillin-1 (FBN1) was shown to be a direct target of miR-486-5p and inversely regulated by miR-486-5p. FBN1 silencing led to decreased PTC cell proliferation and enhanced apoptosis in vitro, similar to that mediated by miR-486-5p. Furthermore, miR-486-5p over-expression or FBN1 knock-down inhibited, while up-regulation of FBN1 boosted xenograft tumor formation in vivo. Our data suggest that miR-486-5p induces PTC cell growth inhibition and apoptosis by targeting and suppressing FBN1. Thus, miR-486-5p/FBN1 might provide a promising therapeutic target for PTC treatment.

BRAF V600E detection in cytological thyroid samples: A key component of the decision tree for surgical treatment of papillary thyroid carcinoma.

Whether preoperative knowledge of the BRAF mutation status would help to determine the extent of surgery for thyroid nodules is still under investigation. We developed a method to state the V600E mutation before surgery on fine-needle aspiration (FNA) stained smears checked to contain tumor cells. We evaluated the interest of the preoperative assessment of the mutation for surgical strategy of nodules, diagnosed as malignant, suspicious for malignancy or follicular neoplasms. The mutation was found in 81% (79 of 97) malignant, 59% (20 of 34) suspicious nodules, and in none of follicular neoplasms (n = 29). Overall, the mutation was detected in 82% of papillary carcinomas. The sensitivity, specificity, and positive and negative predictive values for the diagnosis of malignancy were 75%, 100%, 100%, and 46%, respectively. The preoperative knowledge of the V600E mutation status is fundamental to plan total thyroidectomy with certainty and should be part of the decision tree for the management of thyroid nodules. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1017-1021, 2016.

MiR-137 acts as a tumor suppressor in papillary thyroid carcinoma by targeting CXCL12.

Accumulating evidence has shown that aberrantly expressed microRNAs (miRs) are extensively involved in tumorigenesis. microRNA-137 (miR-137) has been reported as a tumor suppressor in various types of cancer. However, the biological function and underlying molecular mechanism of miR-137 in papillary thyroid carcinoma (PTC) remain largely unknown. Therefore, the present study aimed to investigate the expression pattern of miR-137 and its functional significance in PTC. Quantitative RT-PCR (qRT-PCR) assay showed that miR-137 expression was significantly downregulated in human PTC tissues, and its expression was significantly negatively correlated with tumor-node-metastasis (TNM) stage and lymph node metastasis. Functional assays showed that forced expression of miR-137 in PTC cells significantly inhibited proliferation, colony formation, migration and invasion in vitro. Importantly, on the basis of bioinformatic analysis and luciferase reporter assay, we found that miR-137 directly targeted the 3'-untranslated region (3'-UTR) of C-X-C motif chemokine 12 (also known as SDF-1) (CXCL12). qRT-PCR and western blot analysis further verified the results and demonstrated that miR-137 could downregulate CXCL12 expression in PTC cells. We also confirmed that CXCL12 expression was increased in PTC tissues and was inversely correlated with miR-137. In addition, our results also showed that downregulation of CXCL12 mimicked the effects of miR-137 overexpression, and upregulation of CXCL12 partially reversed the inhibitory effects of miR-137 in PTC cells. These results showed that miR-137 may function as a tumor suppressor in PTC by targeting CXCL12, suggesting that miR-137 may act as a potential target for PTC treatment.

What is the Minimal Surgery for Papillary Thyroid Carcinoma?

Although thyroid surgery for treatment of papillary thyroid carcinoma (PTC) has been practiced for more than 100 years, there is still controversy regarding the minimal surgery needed for cure. The main reason for this controversy is lack of prospective randomized trials. The data accumulated in the last four decades indicate that hemithyroidectomy can be sufficient and safely practiced in low-risk patients with PTC. Patients <45 years of age with a single tumor less than 2 cm, with no lymphatic spread, and in the absence of other risk factors, can be equally managed by hemithyroidectomy or total thyroidectomy. A slight increase in the risk of vocal cord paralysis and hypocalcemia after total thyroidectomy suggests that hemithyroidectomy is appropriate for the management of patients with stage T1 disease. Any choice regarding the extent of surgery should be made with the patient and his family and in a multidisciplinary setup, which has been shown to improve decision-making procedures before the operation and during follow-up.

Identification of Differentially Expressed Kinase and Screening Potential Anticancer Drugs in Papillary Thyroid Carcinoma.

Aim. We aim to identify protein kinases involved in the pathophysiology of papillary thyroid carcinoma (PTC) in order to provide potential therapeutic targets for kinase inhibitors and unfold possible molecular mechanisms. Materials and Methods. The gene expression profile of GSE27155 was analyzed to identify differentially expressed genes and mapped onto human protein kinases database. Correlation of kinases with PTC was addressed by systematic literature search, GO and KEGG pathway analysis. Results. The functional enrichment analysis indicated that “mitogen-activated protein kinases pathway” expression was extremely enriched, followed by “neurotrophin signaling pathway,” “focal adhesion,” and “GnRH signaling pathway.” MAPK, SRC, PDGFRa, ErbB, and EGFR were significantly regulated to correct these pathways. Kinases investigated by the literature on carcinoma were considered to be potential novel molecular therapeutic target in PTC and application of corresponding kinase inhibitors could be possible therapeutic tool. Conclusion. SRC, MAPK, and EGFR were the most important differentially expressed kinases in PTC. Combined inhibitors may have high efficacy in PTC treatment by targeting these kinases.

Over-expression of microRNA-375 inhibits papillary thyroid carcinoma cell proliferation and induces cell apoptosis by targeting ERBB2

MicroRNAs (miRs) played important roles in the cell proliferation, apoptosis and other biological processes in cancer. In the present study we found that miR-375 was significantly down-regulated in human papillary thyroid carcinoma (PTC) tissues and cell lines. In this study we try to investigate the biological activity of miR-375 in human PTC cells and try to find the potential target of miR-375. Our study indicated that over-expression of miR-375 could inhibit the PTC cells proliferation and this inhibition was caused by the induction of cell apoptosis. In vivo animal study indicated that over-expression of miR-375 could significantly decrease the migration and invasion of human PTC cell in vivo. These results exhibit over-expression of miR-375 in human PTC cells could inhibit the process of human PTC. Further study demonstrated ERBB2 was a direct target of miR-375, over-expression of miR-375 decrease the both mRNA and protein expression of ERBB2 in human PTC cells. These data indicate miR-375 play important roles in the process and development of human PTC. These finds suggested that appropriate application of miR-375 regulation might be a new sight for the treatment of human PTC in the future.