Xianying Meng

MicroRNA-497 inhibits thyroid cancer tumor growth and invasion by suppressing BDNF

miR-497 reportedly plays critical roles in tumor development and progression in many types of cancers. We therefore investigated the function and underlying mechanism of miR-497 in thyroid cancer. We found that miR-497 is downregulated in thyroid cancer tissues, and that miR-497 levels are negatively correlated with advanced clinical stage and lymph node metastasis. Overexpressed miR-497 suppressed thyroid cancer cell proliferation, colony formation, migration, and invasion in vitro, and inhibited tumorigenesis in vivo. Moreover, brain-derived neurotrophic factor (BDNF), a known oncogene, was confirmed as a direct target of miR-497 in thyroid cancer cells. miR-497 overexpression suppressed BDNF expression and its downstream pathway(PI3K/AKT)in vitro and in vivo. BDNF levels were upregulated and inversely correlated with miR-497 levels in human thyroid cancer specimens. Rescue experiments showed that forced overexpression of BDNF effectively reversed the tumor suppressive functions of miR-497. These results show that miR-497 is a thyroid cancer tumor suppressor that acts by repressing BDNF.

MicroRNA-454 may function as an oncogene via targeting AKT in triple negative breast cancer

BackgroundAltered microRNAs expression mediates tumor development and progression in many type cancers including triple negative breast cancer (TNBC). Here we detected the effect of miR-454 on cell proliferation, migration and invasion of triple negative breast cancer cells.ResultsmiR-454 promoted the proliferation of TNBC, and enhanced migration and invasion in TNBC cells. Meanwhile, miR-454 improved the survival of TNBC cells after ironizing radiation. miR-454 inhibited radiation-induced apoptosis in TNBC cells by regulation of caspase 3/7 and Bcl-2 expression. Furthermore, PTEN and pAKT levels in TNBC cells were changed after overexpression of miR-454.ConclusionsmiR-454 played an essential role in tumor development and progression in TNBC, and might be used as a potential biomarker to predict radiotherapy response and prognosis in TNBC.

Immunohistochemical levels of cyclo-oxygenase-2, matrix metalloproteinase-9 and vascular endothelial growth factor in papillary thyroid carcinoma and their clinicopathological correlations

Objective To measure the levels of cyclo-oxygenase (COX)-2, matrix metalloproteinase (MMP)-9 and vascular endothelial growth factor (VEGF) immunostaining in papillary thyroid carcinoma (PTC) and benign thyroid tumours, and to investigate potential correlations between their levels and clinicopathological characteristics. Methods The levels of immunohistochemical staining of COX-2, MMP-9 and VEGF proteins were measured in tumours from patients with PTC and compared with specimens from patients with benign thyroid tumours. The association between the levels of COX-2, MMP-9 and VEGF proteins and clinicopathological characteristics in patients with PTC was also analysed. Results A total of 66 patients with PTC and 40 patients with benign thyroid tumours participated in the study. The rates of positive immunostaining for COX-2, MMP-9 and VEGF in PTC tumours were significantly higher than those in benign thyroid tumours. There were significant positive associations between positive immunostaining for COX-2, MMP-9 and VEGF proteins and age (≥45 years), clinical stage (III–IV) and tumour diameter (≥2 cm). Conclusion Combined immunohistochemical evaluation of the levels of COX-2, MMP-9 and VEGF in PTC might be a useful marker for the diagnosis of PTC.

Antitumor activity of celecoxib, a selective cyclooxygenase-2 inhibitor, in medullary thyroid carcinoma

The purpose of this study was to investigate the mechanisms of the antitumor effect of celecoxib (CXB) in the treatment of human medullary thyroid carcinoma (MTC). Human MTC TT cells were cultured with different concentrations (0, 20, 40, 60 µmol/l) of CXB following 0-72 h in vitro. An MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay was used to determine the growth inhibition of MTC in vitro. Flow cytometry was performed to analyze the cell cycle of TT cells. Levels of prostaglandin E2 (PGE2) were measured by enzyme-linked immunosorbent assay (ELISA) method. The expression profile of cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) was measured by western blot analysis. In the present study, it was identified that CXB inhibited TT cell proliferation and induced apoptosis in a dose- and time-dependent manner. The cell cycle was arrested at G0/G1 and the percentage of cells in S phase was markedly decreased. The expression levels of PGE2 were inhibited by CXB. CXB effectively downregulated the expression of COX-2 and VEGF in a dose- and time-dependent manner. These data demonstrated that CXB inhibited the proliferation of MTC TT cells in vitro and thus may be effective as an antitumor therapy for human MTC.

Clinical characteristics and treatment outcomes of parathyroid carcinoma: A retrospective review of 234 cases

Parathyroid carcinoma (PC) is one of the rarest known types of cancer and has a moderate prognosis, with estimated 5- and 10-year overall survival rates between 78–85% and between 49–70%, respectively. To raise awareness of this disease, and to optimize its diagnosis, clinical management and prognosis, the present study retrospectively reviewed 234 cases of PC. A total of 226 cases of PC, which were archived between 1984 and 2015 in the three major databases of the Chinese population, were retrieved and pooled with the 8 cases diagnosed and treated at the Department of Thyroid Surgery of The First Hospital of Jilin University (Changchun, China) between June 2008 and December 2015. The clinicopathological features, diagnosis, surgical procedures and outcomes of these cases of PC were investigated. The review revealed that misdiagnosis has been a considerable issue, with >80% of the patients misdiagnosed prior to surgery, and the accuracy of intraoperative diagnosis based on frozen sections was only 15.04%. The use of radical resection as first-line therapy significantly improved the disease-free survival by ~8 years (log-rank, 20.956; P<0.001); and, at relapse, reoperation prolonged patient survival by ~7 years (log-rank, 35.322; P<0.001). Consistently, a Cox proportional hazards analysis indicated that radical resection as a first-line therapy reduced the risk of postoperative recurrence (P=0.030), and that reoperation following recurrence significantly improved patient survival (P=0.030). The 5- and 10-year cumulative disease-specific survival rates of the cases of PC were 83 and 67%, respectively. Notably, an increased mortality rate was observed among males with PC compared with female patients with PC. In summary, in the past 32 years (1984–2015), the majority of patients with PC have been misdiagnosed. Performing radical resection as the first-line therapy significantly reduces recurrence and improves patient survival time; and, following relapse, subsequent surgery has also been demonstrated to be an effective approach.

Doxorubicin combined with celecoxib inhibits tumor growth of medullary thyroid carcinoma in xenografted mice

The aim of the present study was to investigate the antitumor effect of celecoxib (CXB) combined with doxorubicin (DOX) on the subcutaneous xenograft tumor of medullary thyroid carcinoma in nude mice, and to analyze the possible mechanism of action. Nude mice with xenografted medullary thyroid carcinoma (MTC) were randomly divided into the control, CXB, DOX and DOX plus CXB groups, and the drug treatment was administered for three weeks. It was found that the tumor inhibition rates and the apoptosis index in the treatment groups were higher than in the control group (P<0.01), and that these values were higher in the combination group compared with the single-drug group (P<0.01). DOX alone upregulated the cyclooxygenase-2 and multidrug-resistance 1 expression levels, and the combination of CXB and DOX or CXB alone notably decreased the expression level of the two proteins compared with no treatment. The results of the present study provide evidence that a combination of DOX and CXB is a potential drug candidate for the treatment of MTC.

Coexistence of Medullary Carcinoma and Papillary Carcinoma in the Same Lobe of the Thyroid: A Rare Case Report

We report a rare case of coexistence of medullary thyroid carcinoma (MTC) and papillary thyroid carcinoma (PTC) in the right thyroid lobe. A 60-year-old female patient was diagnosed with MTC and PTC after right hemithyroidectomy. The extreme rarity of this pathological feature is discussed. While immunohistochemistry for calcitonin and thyroglobulin suggested histogenesis, cytopathology of the biopsy confirmed MTC and PTC. The coexistence of MTC and PTC differs from the most common mixed tumours as both tumors occurred in the single tissue. In conclusion, this case report not only can improve the clinical diagnosis rate of rare cases, but also can avoid reoperation of the patients, and improve survival and the quality of life.

Clinical Research of Regular Pattern of Cervical Lymph Node Metastasis in CN0 Papillary Thyroid Carcinoma

To investigate the regular metastasis pattern of cervical lymph nodes in CN0 papillary thyroid carcinoma and to define the proper surgery scope. Clinical data of the 1208 cases of CN0 papillary thyroid carcinoma patients undergoing surgery from Feb.2008 to Feb.2016 in the First Hospital of Jilin University were retrospectively analyzed. There were 572 (47.35%) PN+ cases and 636 (52.65%) PN0 cases. In CN0 cases, lymph node metastasis was most commonly detected in area VI, which was about 45.94%(555/1208). When the tumor diameter was no less than 1.0cm, multifocal or capsule invaded, male,

Research on Influence Factors and Clinical Significance of Delphian Lymph Node Metastasis in Papillary Thyroid Carcinoma

Objective To determine the incidence and significance of delphian lymph node metastasis in papillary thyroid cancer(PTC) and evaluate the clinical significance of delphian lymphnode metastasis in PTC patients. Methods We reviewed themedical records of 182 patients with pathologically confirmedPTC who underwent thyroid surgery and were detected delphian lymph nodes between September 2013 and January 2015 in the First Hospital of Jilin University. The relationship between related clinical factors and delphian lymph node metastasis was analyzed. The statistical significance of clinical factors were analyzed by logistic regression analysis, and were to further validate effect. Correlation analysis was carried between positive delphian lymph nodes and central paratracheal and lateral lymph nodes metastasis, the relationship between delphian lymph node metastasis and ipsilateral or contralateral VI region lymph node metastasis was analyzed. Results Delphian lymph node metastasis was related with factors of age, maximum diameter of tumor, capsule invasion, concomitant with Hashimotos thyroiditis. Tumor larger than 1 cm and capsule invasion were the risk factors of delphian lymph node metastasis. Central and lateral lymph node metastasis rates were positive related with the number of metastatic delphian lymph nodes. When tumor was located in one side and with metastatic delphian lymph nodes, the metastasis rates of ipsilateral and contralateral VI region were higher. Conclusion Special attention should be paid on evaluation of delphian lymph nodes and intraoperative exploration. We should determine whether there are metastatic delphian lymph nodes before operationwhen patients have relevant risk factors. Patients with unilateral carcinoma whose delphian lymph nodes determined to be positive should expand the dissection of contralateral lymph node appropriately.

Non-recurrent Inferior Laryngeal Nerve: Clinical Manifestations, Surgical Outcomes, and Literature Review

Background: The most serious complication of thyroidectomy and parathyroidectomy is recurrent laryngeal nerve (RLN) injury. Recurrent laryngeal nerve is known to have many anatomical variations. The non-recurrent inferior laryngeal nerve(NRLN) is an extremely rare asymptomatic but important anatomical variation, and it is very susceptible to damage during surgery. In this study, we investigated the NRLN variation in a single-institution database. Materials and Methods: A total of 22 patients with NRLN were identified from 5,900 patients who underwent thyroidectomy or parath-yroidectomy in our department between January 2009 and December 2015. Their clinical profiles were retrospectively analyzed. Results: All the 22 NRLNs were right-sided. According to Toniatos classification, 4 cases were type 1, 10 cases were type 2A, and 8 cases were type 2B. Statistical analyses showed no correlation between the incidence of NRLN and potential risk factors (gender, pathology variation, and application of intraoperative nerve monitoring). In the neurophysio-logical monitoring group, the mean operation time for exposure was 4.2±1.8 minutes(n=3), which was significantly shorter(p=0.0004) than that in the non-monitoring group, which was 9.7±2.1 minutes (n=19). No NRLN injury occurred in any of these 22 patients. Conclusion:Thyroid surgeons should be aware of this extremely rare anatomical variation in order to avoid laryngeal nerve damage. Intraoperative neur-ophysiological monitoring can effectively help to identify and preserve the NRLN.