Shuai Xue

Expression of the NOB1 gene and its clinical significance in papillary thyroid carcinoma

Objective The aim of this study was to explore the relationships between expression of the NIN1/RPN12 binding protein 1 homologue gene (NOB1) in papillary thyroid carcinoma tissue and clinicopathological variables. Methods Expression of NOB1 in papillary thyroid carcinoma, normal thyroid and benign thyroid tumour tissue was evaluated at the mRNA and protein levels by real-time fluorescence quantitative reverse transcription–polymerase chain reaction and immunohistochemistry, respectively. Relationships between immunohistochemical scores and several clinicopathological variables were also examined. Results Expression of NOB1 mRNA and protein in papillary thyroid carcinomatissue was significantly higher than in normal thyroid tissue and benign thyroid tissue, while there was no significant difference between normal thyroid tissue and benign thyroid tumour tissue. A high level of NOB1 protein expression was associated with large tumour size and Union for International Cancer Control stage, but was not significantly correlated with sex or age. Conclusions Compared with normal thyroid and benign thyroid tumour tissue, papillary thyroid carcinomas showed higher expression of NOB1, which indicates that the expression level of the NOB1 gene in the thyroid may play a key role in the occurrence and development of papillary thyroid carcinoma.

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.

Silencing NOB1 enhances doxorubicin antitumor activity of the papillary thyroid carcinoma in vitro and in vivo

Doxorubicin (DOX), a broad‑spectrum anthra-cyclin, is in wide clinical use for the treatment and prevention of thyroid cancer. However, the effectiveness of the treatment remains limited due to inherent tumor resistance to DOX. Results of a previous study demonstrated that downregulation of NIN1/RPN12 binding protein 1 homolog (NOB1) expression via adenovirus expression vector carrying NOB1 siRNA (Ad/sh-NOB1) induced cancer apoptosis and increased the radiosensitivity of papillary thyroid carcinoma (PTC) cells. However, whether knockout NOB1 can decrease DOX resistance remains unclear. Therefore, in the present study, the effect of Ad/sh-NOB1 infection, independently or in combination with DOX, was determined in a PTC cell line to identify more effective therapeutics against PTC cancer. Furthermore, tumor growth ability in nude mice was determined to identify the combination treatment effect in tumorigenesis in vivo. The results showed that Ad/sh-NOB1 combined with DOX treatment in PTC cells significantly suppressed proliferation, colony formation, migration and invasion, and induced cell apoptosis and arrest in the G0/G1 stage as compared to Ad/sh-NOB1 or DOX monotherapy. We also found that this combination suppressed the tumor growth of a nude mouse model as compared to Ad/sh-NOB1 or DOX monotherapy. In addition, Ad/sh-NOB1 combined with DOX treatment significantly increased activation of the p38 MAPK pathway, which may contribute to inhibition of PTC cell growth and decreased DOX resistance. Taken together, the experimental results indicate that Ad/sh-NOB1 combined with DOX treatment is a potential drug candidate for the treatment of papillary thyroid carcinoma.

Adenovirus-mediated siRNA targeting NOB1 inhibits tumor growth and enhances radiosensitivity of human papillary thyroid carcinoma in vitro and in vivo

NIN1/RPN12 binding protein 1 homolog (NOB1), a ribosome assembly factor, plays critical roles in tumor progression and development. Previously, we reported that overexpression of NOB1 is correlated with the prognosis of patients with papillary thyroid carcinoma (PTC). Little is known, however, concerning its role in PTC. The aims of the present study were to investigate the association of NOB1 expression with tumor growth and radiosensitivity of human PTC. A recombinant adenovirus expression vector carrying NOB1 was constructed and then infected into the human PTC cell line TPC-1. Cell proliferation, cell cycle distribution, apoptosis, migration and invasion in vitro and tumor growth in vivo were determined after downregulation of NOB1 by RNAi. Additionally, the in vitro and in vivo radiosensitivity of PTC cells was determined by clonogenic cell survival assay and a mouse xenograft model, respectively. The results showed that downregulation of NOB1 expression using RNAi in TPC-1 cells significantly inhibited cell proliferation, migration and invasion and induced cell apoptosis in vitro, and suppressed tumor growth in vivo, as well as enhanced the in vitro and in vivo radiosensitivity of PTC cells. Moreover, our results also showed that downregulation of NOB1 was able to significantly activate constitutive phosphorylation of p38 MAPK, which might contribute to the inhibition of PTC cell growth. These findings suggest that NOB1 may be a potential therapeutic target for the treatment of PTC.

Neck dissection with cervical sensory preservation in thyroid cancer

Thyroid cancer is the most common endocrine malignancy. Recently, controversy has focused on the management of lymph node metastases, which represent approximately 90% of disease recurrences and may require considerable time, effort, and resources to diagnose and treat. Neck dissections play an essential role in the management of head and neck cancer. A modified radical neck dissection (MND) refers to resection of the lymph nodes in levels II through V and often including the central nodes in level VI. When performing modified neck dissection, we recommend to protect more reserved cervical plexus. The purpose is to better protect patients neck skin feeling.

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.

Vorinostat Enhance TRAIL-Induced Apoptosis Via DR5 in Anaplastic Thyroid Cancer Cells

Anaplastic thyroid carcinoma (ATC) is one of the most aggressive human malignancies, which is refractory to surgery, radiotherapy, radioiodine therapy and conventional chemotherapy. Vorinostat (SAHA, also called suberoylanilide hydroxamic acid) is one of Histone deacetylase inhibitors (HDACIs), which is a promising agent for cancer therapy. Death receptor 5 (DR5) is a transmembrane receptor containing death domain that triggers cell death upon binding to TRAIL (tumor necrosis factor-related apoptosis-inducing ligand), and the combination of TRAIL and agents that increase the expression of DR5 is expected as a novel anticancer therapeutic strategy. Here we report that Vorinostat enhanced TRAIL-induced apoptosis in human anaplastic thyroid cancer cells. This effect is to be achieved through increasing expression of DR5 on the cell surface. Our results provide novel options into the therapy of ATC. We hope that these results could contribute to the advancement of the knowledge of this rare and aggressive cancer.

Short and Long-Term Potential Role of Carbon Nanoparticles in Total Thyroidectomy with Central Lymph Node Dissection

Whether we should use carbon nanoparticle (CN) routinely in thyroid surgery is still controversial. 406 papillary thyroid cancer (PTC) patients who underwent total thyroidectomy (TT) with bilateral central lymph node dissection (CLND) from January 2010 to December 2012 were retrospectively analyzed. The incidence of transient hypoparathyroidism and hypocalcemia in CN group was significantly lower than the control group at second, fifth day after surgery (P = 0.004, 0.042, 0.002 and 0.045 respectively). However, no significant difference existed between the two groups about the permanent hypoparathyroidism and hypocalcemia (P = 1.000). Total number of central lymph nodes and metastatic lymph nodes in CN group were more than those in control group (P = 0.031 and 0.038 respectively). However, recurrence was not significantly different between the two groups after at least 5-year follow up (P = 0.7917). In the subgroup of prophylactic and therapeutic CLND study, no significant difference existed between the two groups (P = 0.5295 and 0.8459 respectively). CN significantly help in identifying the parathyroid glands in surgery and increased the number of lymph nodes in central compartment. However, we should not exaggerate the function of CN since it couldn’t improve the permanent hypoparathyroidism and recurrence in PTC patients who underwent TT with bilateral CLND.

Long non-coding RNA LINC00152 promotes cell growth and invasion of papillary thyroid carcinoma by regulating the miR-497/BDNF axis: SUN et al.

Long intergenic non‐coding RNA 152 (LINC00152) was reported to be tightly linked to tumorigenesis and progression in multiple cancers. However, its biological role and modulatory mechanism in papillary thyroid carcinoma (PTC) has not been elucidated. In this study, we determined the expression levels of LINC00152 in PTC tissues and cell lines by quantitative real time polymerase chain reaction (qRT‐PCR). Cell proliferation, colony formation, migration, and invasion were measured by a Cell Counting Kit‐8 assay, colony formation analysis, wound healing, and transwell invasion assay, respectively. A luciferase reporter assay and qRT‐PCR were used to determine whether LINC00152 interacts with miR‐497 directly. We established a xenograft mouse model to examine the underlying molecular mechanism and effect of LINC00152 on tumor growth in vivo. We found that LINC00152 expression was significantly increased in PTC tissues and derived cell lines. LINC00152 knockdown significantly inhibited proliferation, colony formation, migration, and invasion in vitro, and impaired tumor growth in vivo. We revealed that LINC00152 functioned as a competing endogenous RNA to the miR‐497 sponge, downregulating its downstream target brain‐derived neurotrophic factor (BDNF), which is an oncogene in thyroid cancer. These findings suggest that LINC00152 is responsible for PTC cell proliferation and invasion and exerts its function by regulating the miR‐497/BDNF axis.

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,