Wuguo Tian

Long non-coding RNA ANRIL promotes the invasion and metastasis of thyroid cancer cells through TGF-β/Smad signaling pathway

Objective To investigate the effect of antisense non-coding RNA in the INK4 locus (ANRIL) on invasion and metastasis of thyroid cancer (TC). Results ANRIL expression was significantly up-regulated in TC tissues and cells (P < 0.001), and ANRIL expression was significantly different regarding histological grade and LNM (both P < 0.01). The siRNA-mediated ANRIL silencing inhibits proliferation, invasion, and metastasis of TPC-1 and SW579 cells, and lung metastasis, which can be reversed by TGF-β1 siRNA. The mRNA levels of p15INK4b, p14ARF and p16INK4a in TPC-1 and SW579 cells increased significantly after silencing ANRIL (all P < 0.001), and TGF-β1 siRNA could reverse the ANRIL siRNA induced increase of p15INK4b; expressions of TGF-β1 and p-Smad2/3 were increased after silencing ANRIL (both P < 0.05). Materials and methods TC and adjacent normal tissues were collected from 105 TC patients. LncRNA ANRIL expressions were detected by qRT-PCR. The siRNA ANRIL and siRNA TGF-β1 were constructed for TPC-1 and SW579 cell line transfection: si-ANRIL group, si-TGF-β1 group, si-ANRIL + si-TGF-β1 group, negative control group and blank group. Effects of ANRIL silencing on proliferation, invasion and metastasis of TC cells was detected by MTT assay, Transwell assay and tail vein injection of nude mice in vitro and in vivo. TGF-β1 and p-Smad2/3 expressions in TGF-β/Smad signaling pathway were detected by western blot. Conclusions ANRIL may reduce p15INK4B expression through inhibiting TGF-β/Smad signaling pathway, promoting invasion and metastasis of TC cells, and the silencing of ANRIL inhibits the invasion and metastasis of TPC-1 cells.

PTEN/PI3K/AKT protein expression is related to clinicopathological features and prognosis in breast cancer with axillary lymph node metastases

We explored the relations between PTEN/PI3K/AKT expression and clinicopathological characteristics and prognosis in breast cancer patients with and without axillary lymph node metastasis (LNM). Tissues and follow-up data from 142 patients with (LNM group) and 154 without (non-LNM group) metastases were collected. Expression of PTEN/PI3K/AKT was detected using immunohistochemistry staining. With axillary LNM, the positive rate of PTEN was reduced, whereas that of PI3K and AKT was increased. Expression of AKT was negatively correlated with PTEN expression but positively correlated with PI3K expression. Apparent correlations were detected between AKT and axillary LNM with a tumor size of 2 cm or less; between PTEN, PI3K, and AKT and axillary LNM in stage T1 or T2 breast cancer and invasive carcinoma of a nonspecial type; and between PTEN and AKT and axillary LNM of histologic grade I or II tumors and non-triple-negative breast cancer (all P<.05). In the LNM group, the 5-year survival rate of patients with PTEN-positive tumors was higher than that of patients with PTEN-negative lesions; whereas in the non-LNM group, the 5-year survival rate of patients with AKT-positive tumors was lower than that of patients with AKT-negative lesions (both P<.05). Cox regression analysis showed that PTEN expression was an independent prognostic factor for patients with LNM; AKT expression, tumor diameter, pathologic grade, and pathologic type were independent prognostic factors for patients without LNM. In conclusion, TEN/PI3K/AKT proteins are related to the clinicopathological features and prognosis of breast cancer with axillary LNM.

Low expression of long non-coding RNA GAS5 is associated with poor prognosis of patients with thyroid cancer

The study aims to investigate the role of long non-coding RNA (lncRNA) GAS5 in the diagnosis and prognosis of patients suffering from thyroid cancer (TC). A total of 212 patients with TC and 61 patients with benign thyroid tumor were enrolled in the study. Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to detect the lncRNA GAS5 expression in TC and benign tumor tissues. All TC patients were categorized into high-risk and low-risk groups according to the MACIS, AGES and AMES prognostic scoring system. A 5-year follow-up was conducted in order to determine the disease free survival (DFS) rates and overall survival (OS) rates. The associations between lncRNA GAS5 expression and prognosis of TC patients were analyzed by The Kaplan-Meier survival curves and the Cox regression models. There was a decrease in the lncRNA GAS5 expression in TC tissues in comparison to benign tumor tissues. Expression of lncRNA GAS5 showed significant association with tumor node metastasis (TNM) staging, lymph node metastasis and the multiple cancer foci of TC. AMES high-risk patients showed a decreased expression of lncRNA GAS5 expression than the AMES low-risk patients. The AGES and MACIS high-risk patients showed lower lncRNA GAS5 expression than low-risk patients. The survival rate of TC patients with high lncRNA GAS5 expression was higher than that of TC patients with low lncRNA GAS5 expression during the DFS and OS periods. Cox regression analysis indicated that lncRNA GAS5 expression, TNM staging, lymph node metastasis and multiple cancer foci were independent risk factors for poor prognosis in TC patients. LncRNA GAS5 may be closely related to the diagnosis and prognosis of TC.

Comparison of Diagnostic Accuracy of Real-Time Elastography and Shear Wave Elastography in Differentiation Malignant From Benign Thyroid Nodules.

AbstractThyroid nodules are relatively more prevalent in iodine-deficiency area, and the incidence increased sharply in the past decade in these areas. Workup of malignant from benign nodules in clinic was the main problem for managing thyroid nodules.An overall search for the articles about the diagnostic performance of real-time elastography (RTE) and shear wave elastography (SWE) before April 2015 in the databases of PubMed, Embase, and Google scholar. The pooled sensitivity, specificity, and summary receiver operating characteristic (SROC) curve were obtained from individual studies with a random-effects model. Subgroup and meta-regression analysis were also performed.Fifty-six studies involved in 2621 malignant nodules and 7380 benign nodules were contained in our meta-analysis. The pooled sensitivity and specificity of RTE was 83.0% and 81.2%, which is higher than SWE (sensitivity: 78.7%, specificity: 80.5%). The areas under the SROC curve of RTE and SWE were 0.885 and 0.842 respectively. RTE had higher diagnostic value for Caucasians than Asians. Stran ratio (SR) assessment had higher diagnostic performance than elasticity score (ES) system. Similarly, it had higher diagnostic value when malignant nodules were more than 50.In summary, the results revealed that RTE had higher diagnostic performance than SWE in differentiating malignant from benign nodules. However, future international multicenter studies in the region of thyroid risk need to further assess the diagnostic performance of RTE.

Roles of microRNA-124a and microRNA-30d in breast cancer patients with type 2 diabetes mellitus

The aim of the study is to explore roles of microRNA (miR)-124a and miR-30d in breast cancer (BC) patients with type 2 diabetes mellitus (T2DM). A total of 144 cases of confirmed diagnosed BC with T2DM, T2DM, BC, or healthy people were enrolled. Among them, BC patients with T2DM were regarded as the experiment group (n = 36), patients with T2DM as the Dm group (n = 36), patients with BC as the Bc group (n = 36), and healthy subjects as the healthy group (n = 36). The fasting insulin resistance index, glycosylated hemoglobin, and estradiol were measured. MiR-124a and miR-30d expressions were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The insulin resistance index was significantly higher in the experiment group compared to the other three groups (all P < 0.05). The glycated hemoglobin was in a normal range in the Bc group and healthy group, but was higher in the experiment group and the Bc group compared to that in the healthy group (both P < 0.05). The serum estradiol level was obviously higher in the Bc group compared with that in the Dm group and the experiment group (both P < 0.05). The expressions of miR-124a and miR-30d were positively correlated with insulin resistance index, BMI and glycosylated hemoglobin (miR-124a r = 0.659, r = 0.785, and r = 0.862; miR-30d r = 0.742, r = 0.805, r = 0.765; all P < 0.001). Insulin resistance index was an independent factor for expressions of miR124-a and miR-30d. MiR-124a and miR-30d were correlated with insulin resistance and development of BC with T2DM. Although the mechanism is not clear, miR-124a and miR-30d potentially may be used as therapeutic targets and prognostic markers for BC patients with T2DM.

Comparing the Diagnostic Accuracy of RTE and SWE in Differentiating Malignant Thyroid Nodules from Benign Ones: a Meta-Analysis.

Background: Approximately 10-20 million Americans have been clinically diagnosed with thyroid nodules. Shear wave elastography (SWE) and real-time elastography (RTE) are two primary forms of elastography for identifying the status of thyroid nodules. The aim of this study is to assess the performance of RTE and SWE in identifying malignant thyroid nodules. Methods: Relevant articles were systematically retrieved from PubMed, Embase and Cochrane Library. In order to evaluate the overall diagnostic accuracy, we have considered pooled sensitivity (SEN), specificity (SPE), area under the curve (AUC) and partial AUC with corresponding 95% confidence intervals (95%CIs). Stratified analyses by ethnicity (Caucasian, Asian), the number of malignant nodules (> 50, < 50), score system (elasticity scores: ES and strain ration: SR) and ES (> 4, < 4) were performed to explore potential sources of heterogeneity. All statistical tests were performed using the R 3.2.1 software package. Results: We analyzed 80 trials from 71 studies with 16,624 subjects (12,348 for SWE, 4,276 for RTE). The pooled results suggested that RTE is more accurate than SWE in diagnosing malignant cases (RTE: SEN= 0.829, 95%CI = 0.799-0.855, SPE = 0.828, 95%CI = 0.789-0.862, AUC = 0.889; SWE: SEN = 0.784, 95%CI = 0.732-0.828, SPE = 0.824, 95%CI = 0.766-0.871, AUC = 0.859). No significant difference was found in the subgroup analyses. Conclusion: Our findings revealed that RTE is superior to SWE in differentiating malignant and benign thyroid nodules. Nevertheless, more studies focusing on the diagnostic accuracy of RTE and SWE during different stages of thyroid nodules development should be carried out in the future.

MicroRNA-107 is downregulated and having tumor suppressive effect in breast cancer by negatively regulating BDNF

In the present study, we investigated the possible tumor suppressive effect of microRNA‐107 (miR‐107) in human breast cancer.

A network meta-analysis for toxicity of eight chemotherapy regimens in the treatment of metastatic/advanced breast cancer

Objective To compare the incidence of toxicity of 8 different chemotherapy regimens, including doxorubicin + paclitaxel, doxorubicin, capecitabine, CMF (cyclophosphamide + methotrexate + 5-fluorouracil), FAC (fluorouracil + doxorubicin + cyclophosphamide), doxorubicin + docetaxel, doxorubicin + cyclophosphamide and paclitaxel in the treatment of metastatic/advanced breast cancer. Results This network meta-analysis included 8 randomized controlled trials (RCTs). The findings revealed that, with regard to capecitabine alone regimen exhibited higher incidence of nausea/vomiting than doxorubicin + paclitaxel regimen, doxorubicin alone regimen and paclitaxel alone regimen in the treatment of patients with metastatic/advanced breast cancer (OR = 32.48, 95% CI = 1.65~2340.57; OR = 22.75, 95% CI = 1.03~1923.52; OR = 59.63, 95% CI = 2.22~5664.88, respectively). Furthermore, doxorubicin + cyclophosphamide regimen had lower incidence of febrile neutropenia than doxorubicin + docetaxel (OR = 0.17, 95% CI = 0.03~0.96). No significant difference in the incidence of stomatitis was observed among eight chemotherapy regimens. Materials and Methods We initially searched PubMed, Cochrane Library and Embase databases from the founding of these databases to January 2016. Eligible studies investigating the 8 different chemotherapy regimens for treatment of metastatic/advanced breast cancer were included for direct and indirect comparison. The odds ratio (OR) and surface under the cumulative ranking curves (SUCRA) value of the incidence of toxicity among eight chemotherapy regimens were analyzed. Conclusions Capecitabine alone regimen and doxorubicin + docetaxel regimen may have a more frequent toxicity in the treatment of metastatic/advanced breast cancer.

Peri-operative treatment of giant nodular goiter.

Objective: To summarize the experience in the peri-operative treatment of giant nodular goiter. Methods: A total of 123 patients with giant nodular goiter sized 6~20 cm were admitted into our hospital from 1990 to 2011 and the clinical data were retrospectively analyzed. These patients underwent total or subtotal thyroidectomy. Results: All patients underwent surgical intervention. Unilateral subtotal thyroidectomy was performed in 40 patients, unilateral total thyroidectomy in 1 patient, bilateral subtotal thyroidectomy in 79 patients, and unilateral total thyroidectomy, removal of entire isthmus and contralateral subtotal thyroidectomy in 3 patients. Nodular goiter was pathologically proven post-operatively. No short-term complications such as dyspnea or thyroid storm were found postoperatively. Post-operative follow up was done for 9 months to 6 years and no recurrence was observed. Conclusion: Comprehensive pre-operative preparation, pre-operative evaluation, complete exposure of the operative field, meticulous operation, effective control and prevention of hemorrhage and prevention against damage to superior and recurrent laryngeal nerves are crucial for the successful surgical intervention of giant nodular goiter.

Does dual HER-2 blockade treatment increase the risk of severe toxicities of special interests in breast cancer patients: A meta-analysis of randomized controlled trials

Although dual HER-2 blockade treatment could offer greater clinical efficacy in breast cancer, the risk of severe toxicities of special interest related to this combined regimen in breast cancer remained unknown. We systematically searched public databases (MEDLINE, EMBASE, Cochrane library) to identify relevant studies that comparing anti-HER2 monotherapy (lapatinib or trastuzumab or pertuzumab) with dual HER-2 blockade treatment (pertuzumab plus trastuzumab or trastuzumab plus lapatinib) in breast cancer. A total of 11,941 breast cancer patients from 9 trials were included for analysis. Meta-analysis showed that dual HER2 blockade treatment significantly increased the risk of severe diarrhea (OR 2.52, p<0.001) and treatment discontinuation (OR 1.52, p=0.014), but not for severe rash (OR 1.06, p=0.81), liver toxicities (OR 1.16, p=0.28), CHF (OR 1.46, p=0.09), LVEF decline (OR 1.09, p=0.40) and FAEs (OR 0.97, p=0.91). Similar results were observed in sub-group analysis according to anti-HER2 regimens in terms of severe diarrhea and treatment discontinuation. Additionally, trastuzumab plus lapatinib significantly increased the risk of LVEF decline in comparison with lapatinib alone (OR 1.48, p=0.002). Our analysis indicated that dual anti-HER2 blockade treatment significantly increased the risk of developing severe diarrhea and treatment discontinuation in comparison with anti-HER2 monotherapy. These were no evidence of an increased risk of fatal adverse events with dual-HER2 blockade treatment.