No abstract

Trastuzumab is widely used in the clinical treatment of human epidermal growth factor receptor-2 (HER2)-positive breast cancer, but the patient response rate is low. CD147 stimulates cancer cell proliferation, migration, metastasis and differentiation and is involved in chemoresistance in many types of cancer cells. Whether CD147 alters the effect of trastuzumab on HER2-positive breast cancer cells has not been previously reported. Our study confirmed that CD147 suppression enhances the effects of trastuzumab both in vitro and in vivo. CD147 suppression increased the inhibitory rate of trastuzumab and cell apoptosis in SKBR3, BT474, HCC1954 and MDA-MB453 cells compared with the controls. Furthermore, CD147 knockdown increased expression of cleaved Caspase-3/9 and poly (ADP-ribose) polymerase (PARP) and decreased both mitogen-activated protein kinase (MAPK) and Akt phosphorylation in the four cell lines. In an HCC1954 xenograft model, trastuzumab achieved greater suppression of tumor growth in the CD147-knockdown group than in the shRNA negative control (NC) group. These data indicated that enhancement of the effect of trastuzumab on HER2-positive cells following CD147 knockdown might be attributed to increased apoptosis and decreased phosphorylation of signaling proteins. CD147 may be a key protein for enhancing the clinical efficacy of trastuzumab.

The aim of the study was to assess the diagnostic value of high b-value (2000 s/mm2) diffusion-weighted imaging (DWI) in differentiating malignant from benign thyroid micronodules.Consecutive patients with thyroid micronodules scheduled for Ultrasound (US)-guided fine-needle aspiration biopsy (FNAB) or surgery were underwent high b-value DWI with 3 b-values: 0, 800, and 2000 s/mm2. Signal intensity ratios (SIRs) of thyroid micronodules to adjacent normal thyroid tissue on DWI were measured as SIRb0, SIRb800 and SIRb2000. Apparent diffusion coefficients (ADCs) according to the three different b-values were acquired as: ADCb0–800, ADCb0–2000 and ADCb0–800–2000. The 6 diagnostic indicators were evaluated by receiver operating characteristic (ROC) and diagnostic ability was compared between the high b-value DWI and US.Sixty-two malignant thyroid micronodules (48 patients, 13 men and 35 women, aged 44.8 ± 11.7 years) and 57 benign thyroid micronodules (40 patients, 6 men and 34 women, aged 49.6 ± 12.5 years) were enrolled into the final statistical analysis. Among the alone diagnostic indicators, SIRb2000 had the highest diagnostic ability in differentiating malignant from benign thyroid micronodules with area under curve (AUC) of 0.975, sensitivity of 90.32% and specificity of 96.49%. Compared to US, SIRb2000 had a significantly better diagnostic ability US for thyroid micronodules (P < .001) with dramatically raised positive predict value (96.6% vs 78.9%) and reduced false-positive rate (3.51% vs 26.32%).High b-value (2000 s/mm2) DWI can contribute to differentiating malignant from benign thyroid micronodules.

PurposeThe aim of the study was to evaluate the role of high b-value (2000 sec/mm2) diffusion-weighted imaging (DWI) by using Readout Segmentation of Long Variable Echo-trains (RESOLVE) in differentiating papillary thyroid carcinomas (PTCs) and papillary thyroid microcarcinomas (PTMCs) from benign thyroid nodules.Materials and methodsConsecutive patients with thyroid nodules scheduled for surgery underwent high b-value DWI with 3 b-values: 0, 800 and 2000 sec/mm2. Signal intensity ratios (SIRs) of thyroid nodules to adjacent normal thyroid tissue on DWI were measured as: SIRb0, SIRb800 and SIRb2000. Apparent diffusion coefficient (ADC) values based on the 3 different b-values were acquired as: ADCb0-800, ADCb0-2000, and ADCb0-800-2000. The 6 diagnostic indicators were evaluated by receiver operating characteristic (ROC) and diagnostic ability was compared between high b-value DWI and Ultrasound (US).ResultsA total of 52 PTCs including 33 PTMCs (38 patients, 8 men and 30 women, aged 45.68 ± 11.93 years) and 62 benign thyroid nodules (46 patients, 7 men and 39 women, aged 48.73 ± 11.98 years) were enrolled into the final statistical analysis. ADCb0-800-2000 had the highest diagnostic ability in differentiating PTCs from benign thyroid nodules with area under curve (AUC) of 0.944, sensitivity of 96.15% and specificity of 85.48%, and PTMCs from benign thyroid nodules with AUC of 0.940, sensitivity of 93.94% and specificity of 85.48%. On the strength of lower false-positive rates than US (14.52% vs. 32.26% for PTCs and 14.52% vs. 32.26% for PTMCs), ADCb0-800-2000 had significantly better diagnostic ability in PTCs (P = 0.002) and PTMCs (P = 0.005).ConclusionHigh b-value (2000 sec/mm2) DWI can contribute to differentiating PTCs and PTMCs from benign thyroid nodules and can be potentially used as an active surveillance imaging method for PTMCs.

The purpose of this study was to investigate the expression of Y-Box-binding protein 1 (YB-1) in breast cancer and its correlation with clinicopathological characteristics and prognosis. Paraffin sections were retrospectively collected from 239 cases of stage I-III breast cancer patients and 30 healthy females who received surgery between January 2000 and December 2004 in the Chinese People's Liberation Army General Hospital. The protein expression of YB-1 was detected by immunohistochemistry. The expression difference between the two groups and the correlation between YB-1 expression and clinicopathological characteristics and breast cancer prognosis were analyzed. Within the breast cancer group, YB-1 was expressed in the cytoplasm in 100.0% (239/239) of cases and in the nucleus in 36.8% (88/239) of cases. Within the control group of normal breast tissue, YB-1 was expressed in the cytoplasm in 100.0% (30/30) of cases and in the nucleus in 16.7% (5/30) of cases. The expression of YB-1 in the nucleus of breast cancer cells was significantly higher than that in normal breast tissue (P = 0.029). The expression of YB-1 in the nucleus of breast cancer cells positively correlated with the Scarff-Bloom-Richardson grade (P = 0.007) and HER-2 expression (P = 0.005), negatively correlated with ER expression (P = 0.004), and was independent of the age, menstrual status, pathological type, tumor size, lymph node status, presence of thrombosis, PR expression, and EGFR expression. The 5-year disease-free survival (DFS) and overall survival (OS) of patients with positive YB-1 expression in the nucleus were significantly lower than those of patients who were negative for nuclear YB-1 expression, and the difference was statistically significant (DFS 65.9% vs. 82.1%, P = 0.000; OS 79.5% vs. 92.1%, P = 0.000). Multivariate analysis suggested that the expression of YB-1 in the nucleus is an independent prognostic factor that affects DFS and OS in breast cancer patients (DFS P = 0.015; OS P = 0.035). In conclusion, the expression of YB-1 in the nucleus is related to carcinogenesis and the development of breast cancer. Therefore, YB-1 is an important molecular marker that can be used to predict breast cancer prognosis.