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Breast cancer is the most commonly diagnosed cancer among women, causing 15% of patient deaths. The metastasis of breast cancer cells is the leading cause of death for patients. Several studies have shown that Discoidin Domain Receptor 1 (DDR1) was highly expressed in breast cancer and could influence tumor cell behaviors. However, the specific role of DDR1 in breast cancer metastasis is still elusive. In this study, we uncovered that DDR1 is significantly increased in breast cancer and inversely correlated with the prognosis of patients. Knockdown of DDR1 suppressed the migration and invasion of breast cancer cells. Additionally, overexpression of DDR1 enhanced the metastatic capacity of cancer cells. Immunoblotting revealed that activation of Src and FAK, which are involved in cancer cell metastasis, were correlated with the expression level of DDR1. Co-immunoprecipitation experiments showed that DDR1 could bind to Src and FAK. Finally, the inhibition of FAK and Src could attenuate DDR1 enhanced migration ability of breast cancer cells. In summary, our study revealed that DDR1 was highly expressed in breast cancer and negatively correlated with the prognosis of breast cancer patients. DDR1 facilitates migration and invasion in breast cancer cells via activation of the Src-FAK signaling. Accordingly, blocking DDR1/Src/FAK axis is a promising therapeutic strategy for breast cancer treatment.

This study was initiated to evaluate the clinical significant of HER2 extracellular domain (ECD) in the real-time management of breast cancer patients.Five-hundred forty-six eligible breast cancer patients were divided according to their clinical background. The correlation between ECD, tissue HER2, and clinical outcome of the patients were analyzed.Receiver operating characteristic analysis revealed that ECD measured before receiving neoadjuvant therapy yielded the highest area under the curve (0.9185; P0.0001), indicating that ECD and tissue HER2 levels are consistent in untreated tumor-bearing patients. At cut-off of 15.0ng/ml, the prognostic value of ECD was demonstrated using univariate (HR=1.664, P0.0001) and multivariate (HR=1.547, P=0.011) Cox regression analysis. Kaplan-Meier survival curves revealed that patients with elevated ECD had shorter progression-free survival (PFS) (4.0 vs. 6.1months, P0.0001). Elevated ECD was also an adverse predictor for PFS in response to anti-HER2 therapy (4.3 vs. 10.2months, P=0.0155). In contrast, ≥20%, decreased ECD was associated with longer PFS in patients who received anti-HER2 therapy (10.9 vs. 2.4months, P=0.0164) and overall (10.7 vs. 2.8months, P=0.0034).A patient's clinical history can help determine whether ECD could provide added value for breast cancer management.

To evaluate the efficacy and safety of trastuzumab plus capecitabine as first-line therapy for HER-2-positive metastatic breast cancer patients who have previously received anthracyclines and taxanes.The patients who have HER-2-positive breast cancer recurrence and metastasis after treated by anthracyclines and taxanes were enrolled in this study. The patients received trastuzumab (6 mg/kg every 21 days following a loading dose of 8 mg/kg on cycle 1) and capecitabine (2 000 mg/m², days 1 to 14 every 21 days).38 patients were enrolled. The median PFS for trastuzumab plus capecitabine was 8.6 months. The objective response rate (ORR) was 31.6%. Clinical benefit rate (CBR) was 65.8%. The most serious adverse event was leucopenia in one patient. Relatively common hematology toxicity was grade I or II leucopenia and neutropenia. The most common nonhematologic toxicity was hand-foot syndrome (HFS), which observed in 8 patients (21%). The morbidity of grade II and III HFS were 8% and 3% respectively.Trastuzumab plus capecitabine is an effective and safe regimen as first-line treatment for HER-2-positive metastatic breast cancer patients whose cancer is resistant to treatment with anthracyclines and taxanes.

To evaluate the serum HER2 ECD level and its significance in advanced breast cancer patients with different molecular subtypes.A total of 322 advanced breast cancer patients were enrolled. The serum HER2 ECD concentrations were quantitatively detected by enzyme-linked immunosorbent assay(ELISA). Its relationship with clinicopathological characteristics and clinical significance were analyzed.It was found that 55.9% (19/34)Luminal A, 42.7% (44/103) Luminal B-HER2(-), 70.6% (60/85) Luminal B-HER2(+), 73.8% (45/61)HER2-enriched and 23.1% (9/39) triple-negative patients had serum concentrations of HER2 ECD at least 15 ng/ml respectively. The prevalence of elevated ECD level in patients of different molecular subtypes differed significantly (P0.001). Tissue HER2 status, number of metastatic sites, visceral metastasis, CA15-3 and carcinoembryonic antigen(CEA) levels exhibited statistically significant correlations with the prevalence of elevated serum HER2 ECD level. The serum concentrations of HER2 ECD decreased after effective targeted therapy in tissue HER2-positive patients.The prevalence of elevated serum levels of HER2 ECD differed significantly in advanced breast cancer patients with different molecular subtypes. The serum HER2 ECD level may reflect both histological HER2 status and tumor load. And the dynamic changes of ECD concentrations are somewhat correlated with the efficacies of targeted treatment.

The objective of this study was to evaluate the utility of vestibular autorotation test in the diagnosis of BPPV.VAT and caloric test were performed on 41 patients with BPPV. VAT results were analyzed according to the affected semicircular canal.Results of VAT were abnormal in 34 (82.93%) patients with BPPV. Fourteen cases were found with abnormal vertical phase, 1 case with abnormal vertical gain in a total of 21 vertical semicircular canal BPPV patients. Six cases with abnormal horizontal phase lead, 5 cases with abnormal horizontal gain, 2 cases with asymmetry were found in 12 patients with horizontal semicircular canal BPPV. Phase lead was abnormal in all frequencies in 4 patients, and in 2-3 Hz in 21 patients. 24 (58.54%) patients showed abnormal canal paresis (CP) and direction preference (DP) in caloric test.VAT can indicate information of vestibular function in both vertical and horizontal semicircular canal. Phase of VAT is constantly enhanced in BPPV, especially in 2-3 Hz. As the supplement of caloric test, VAT may prove helpful in assessment of semicircular canal function.

To analyze and outline patterns of hearing disorders in normal otoacoustic emissions.Tests of pure tone audiometry, acoustic impedance test, auditory brainstem response (ABR), 40 Hz AERP,spontaneous otoacoustic emissions (SOAE), transient evoked otoacoustic emissions (TEOAE), distortion evoked otoacoustic emissions (DPEOAE)and imaging examinations of CT/MRI scan were performed on all 83 patients with hearing disorders.Patterns of hearing disorders in normal otoacoustic emissions including (1) 68 patients with auditory neuropathy; (2) 2 patients with unilateral acoustic neuroma; (3) 3 patients with cortical deafness or central hearing loss; (4) 2 patients with hyperacusis; (5) 2 patients with functional deafness; (6) 6 patients with malingering.OAE tests play an important role in diagnosis and differential diagnosis of the patients with retrocochlear deafness, central hearing loss, nonorganic hearing loss and some other special hearing disorders.