[Clinical observational study of Nimotuzumab combined with concurrent chemoradiotherapy in the treatment of locally advanced cervical cancer].

Objective: To investigate the clinical efficacy and safety of Nimotuzumab combined with concurrent chemoradiotherapy in the treatment of locally advanced cervical cancer. Methods: A total of 65 patients with locally advanced cervical cancer treated with Nimotuzumab combined with concurrent chemoradiotherapy in Tianjin Medical University Cancer Institute and Hospital were selected from January 2015 to November 2018. Intensity-modulated radiotherapy and intracavitary post-packaging were used for radiation therapy. Platinum and paclitaxel were used for chemotherapy. Nimotuzumab were 400 mg/week. The clinical efficacy, the changes of serum tumor markers and the occurrence of adverse events were observed for 2 years, and the evaluation was performed once for every 3 months. Results: Sixty-one cases could be evaluated by imaging during the follow-up. The best curative effect evaluation showed that complete remission (CR) was 43 (70.5%), partial remission (PR) was 9 (14.8%), stable disease (SD) was 6 (9.8%) and objective response rate (CR+PR) was 85.3%, disease control rate (CR+PR+SD) was 95.1%. Survival analysis showed that one-year overall survival rate was 93.9% and two-year overall survival rate was 79.6%. After 3 months of treatment, the serum tumor markers SCC, CA125, CEA, and HE4 were significantly lower than those before treatment (P<0.05). Safety assessments showed that the main adverse events were hematochezia, abdominal pain, diarrhea, fever and dizziness, and 37 cases of them were grades Ⅰ-Ⅱ. Conclusion: Nimotuzumab combined with concurrent chemoradiotherapy has a good clinical effect in the treatment of locally advanced cervical cancer, significantly reduces serum tumor marker levels after treatment, and is safe and tolerable in clinical use.

Elastosonography and two-dimensional ultrasonography in diagnosis of axillary lymph node metastasis in breast cancer.

AIM: To compare diagnostic value of two-dimensional (2D) ultrasonography and elastosonography for suspected axillary lymph node metastasis of breast cancer. MATERIALS AND METHODS: Elastosonography and 2D ultrasonography were performed on 78 axillary lymph nodes of 78 patients with suspected breast cancer. Scores of shape, long- to short-axis ratio, cortical thickness, and lymph node hilum were summed as the score of each lymph node at 2D ultrasonography, while a four-point scale was adopted for elasticity scoring. The combined score of each lymph node was obtained by summing the score at 2D ultrasonography and that at elasticity scoring. The strain ratio was calculated by comparison of the average strain of the lymph node with that of the subcutaneous tissue. Diagnostic efficacies of 2D ultrasonography, elasticity scoring, and the combined method were compared. RESULTS: There were 78 axillary lymph nodes, including 34 non-metastatic and 44 metastatic nodes. The elasticity scores of non-metastatic and metastatic axillary lymph nodes were 1.44±0.82 and 3.11±0.75, respectively (p<0.05). The difference in area under the operating characteristic curve (AUC) was statistically significant between 2D ultrasonography and the combined method (p<0.05). The sensitivity, specificity, and accuracy of 2D ultrasonography and elasticity scoring were 77.3% versus 86.4%, 76.5% versus 85.3%, and 76.9% versus 85.9%, respectively (all p>0.05), and those of the combined method were 93.2%, 73.5%, and 84.6%, respectively. There was a significant difference in sensitivity between 2D ultrasonography and the combined method (p<0.05). CONCLUSIONS: Combined application of 2D ultrasonography with elastosonography can improve the diagnostic capability for metastatic axillary lymph node characterisation in breast cancer.

Hrd1 facilitates tau degradation and promotes neuron survival.

Intraneuronal accumulation of abnormal phosphorylated tau (p-tau) is a molecular pathology in many neurodegenerative tauopathies, including Alzheimer's disease (AD) and frontotemporal dementia with parkinsonism-linked to chromosome 17 (FTDP-17). However, the underlying mechanism remains unclear. Here, we showed an inverse relationship between endoplasmic reticulum membrane ubiquitin ligase (E3) Hrd1 expression and p-tau accumulation in the hippocampal neurons of AD, and proposed that Hrd1 may be a negative regulator of p-tau. This notion was further supported by in vitro study demonstrating that Hrd1 interacted with tau and promoted the degradation of total tau and p-tau as well. The degradation of tau depended on its Hrd1 E3 activity. Knockdown of endogenous Hrd1 with siRNA stabilized tau levels. In addition, inhibition of proteasome maintained tau level and increased Hrd1-mediated tau ubiquitination, suggesting the proteasome was involved in tau/p-tau degradation. Over-expression of Hrd1 significantly alleviated tau cytotoxicity and promoted cell survival. These results indicated that Hrd1 functions as an E3 targeting tau or abnormal p-tau for proteasome degradation. The study provides an important insight into the molecular mechanisms of human tauopathies.