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Background: Sentinel lymph node biopsy (SLNB) in breast cancer patients with positive clinical axillary lymph nodes (cN1+) remains a topic of controversy. The aim of this study is to assess the influence of various axillary and breast surgery approaches on the survival of cN1+ breast cancer patients who have responded positively to neoadjuvant therapy (NAT). Methods: Patients diagnosed with pathologically confirmed invasive ductal carcinoma of breast between 2010 and 2020 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. To mitigate confounding bias, propensity score matching (PSM) analysis was employed. Prognostic factors for both overall survival (OS) and breast cancer-specific survival (BCSS) were evaluated through COX regression risk analysis. Survival curves were generated using the Kaplan-Meier method. Furthermore, cumulative incidence and independent prognostic factors were assessed using a competing risk model. Results: The PSM analysis matched 4,890 patients. Overall survival (OS) and BCSS were slightly worse in the axillary lymph node dissection (ALND) group (HR = 1.10, 95% CI 0.91-1.31, p = 0.322 vs. HR = 1.06, 95% CI 0.87-1.29, p = 0.545). The mastectomy (MAST) group exhibited significantly worse OS and BCSS outcomes (HR = 1.25, 95% CI 1.04-1.50, p = 0.018 vs. HR = 1.37, 95% CI 1.12-1.68, p = 0.002). The combination of different axillary and breast surgery did not significantly affect OS (p = 0.083) but did have a significant impact on BCSS (p = 0.019). Competing risk model analysis revealed no significant difference in the cumulative incidence of breast cancer-specific death (BCSD) in the axillary surgery group (Grey's test, p = 0.232), but it showed a higher cumulative incidence of BCSD in the MAST group (Grey's test, p = 0.001). Multivariate analysis demonstrated that age ≥ 70 years, black race, T3 stage, ER-negative expression, HER2-negative expression, and MAST were independent prognostic risk factors for both OS and BCSS (all p < 0.05). Conclusion: For cN1+ breast cancer patients who respond positive to NAT, the optimal surgical approach is combining breast-conserving surgery (BCS) with SLNB. This procedure improves quality of life and long-term survival outcomes.

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Eph receptors are the largest subfamily of receptor tyrosine kinases, and they have been shown to play a crucial role in glioma. The EphB3 receptor is a member of this family, and its effect on the invasion, migration and proliferation of glioma cells was examined in this study. It was found that the expression of EphB3 was decreased in glioma specimens with increasing tumor grade. Additionally, the U87MG and U251 cell lines showed low levels of EphB3 expression. This finding was consistent with the negative correlation between EphB3 expression in glioma tissues and tumor grade. Depletion of EphB3 gene in U87MG and U251 cell lines resulted in a substantial enhancement of their invasion, migration, and proliferation capacities in vitro. Furthermore, the knockdown of EphB3 led to an upregulation of EGFR, p-PI3K, and p-AKT protein levels. On the other hand, EphB3 overexpression reduced the invasiveness, proliferative capacity and migration rate of U87MG and U251 cells, and downregulated EGFR, p-PI3K and p-AKT. These findings indicate that EphB3 functions as a tumor suppressor in glioma, and its downregulation enhances the malignant potential of glioma cells by activating the EGFR-PI3K/AKT pathway. Thus, EphB3 is a promising diagnostic marker for glioma, and the EphB3-EGFR-PI3K / AKT axis deserves further investigation as a potential therapeutic target.

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BACKGROUND: KIFC1 exerts an important function in centrosome aggregation in breast cancer (BC) cells and a variety of other cancer cells, but its potential mechanisms in BC pathogenesis are yet fully elucidated. The aim of this study was to investigate the effects of KIFC1 on BC progression and its underlying mechanisms. METHODS: Expression of ELK1 and KIFC1 in BC was analyzed by The Cancer Genome Atlas database and quantitative real-time polymerase chain reaction. Cell proliferative capacity was examined by CCK-8 and colony formation assays, respectively. Glutathione (GSH)/glutathione disulfide (GSSG) ratio and GSH level were measured using the kit. Expression of GSH metabolism-related enzymes (G6PD, GCLM, and GCLC) was detected by western blot. Intracellular reactive oxygen species (ROS) levels were measured by the ROS Assay Kit. The transcription factor ELK1 upstream of KIFC1 was identified by hTFtarget, KnockTFv2 database and Pearson correlation. Their interaction was validated by dual-luciferase reporter assay and chromatin immunoprecipitation. RESULTS: This study demonstrated the upregulation of ELK1 and KIFC1 in BC and found that ELK1 could bind to the KIFC1 promoter to promote KIFC1 transcription. KIFC1 overexpression increased cell proliferation and intracellular GSH levels, while decreasing intracellular ROS levels. The addition of the GSH metabolism inhibitor BSO attenuated the promotion of BC cell proliferation induced by KIFC1 overexpression. In addition, KIFC1 overexpression reversed the inhibitory effect of knockdown of ELK1 on BC cell proliferation. CONCLUSION: ELK1 was a transcriptional factor of KIFC1. ELK1/KIFC1 axis reduced ROS level by increasing GSH synthesis, thus facilitating BC cell proliferation. Current observations suggest that ELK1/ KIFC1 may be a potential therapeutic target for BC treatment.

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Background: Sentinel lymph node biopsy (SLNB) has been recommended as a replacement for axillary lymph node dissection (ALND) in male breast carcinoma (MBC) with clinical axillary lymph node-negative (ALN-negative) as in the case of female. However, the morbidity after SLNB may also have short-term or long-term complications. To avoid unnecessary surgery, building a model which is able to assess the risk of lymph node metastasis is vitally significant. Methods: A retrospective review of the clinical and pathology data were carried out for patients diagnosed with MBC between 2010 and 2018 from the Surveillance, Epidemiology, and End Results (SEER) database. The cohort was divided into training and validation cohorts. A logistic regression model was used to construct the nomogram in the training cohort and then verified in the validation cohort. The receiver operating characteristic (ROC) curve, C-index, and calibration were used to evaluate the predictive ability of the nomogram. Results: Overall, 2,610 patients diagnosed with MBC were included in the study, of which 1,740 were in the training cohort and 870 were in the validation cohort. Logistic regression analysis indicated age at diagnosis, tumor location, tumor stage, pathological type, and histologic grade, were significantly related to axillary lymph node metastasis (ALNM). The area under the curve (AUC) of the nomogram was 0.846 (95% CI: 0.825-0.867) and C-index was 0.848 (95% CI: 0.807-0.889), demonstrating a notable prediction performance. The calibration curve for the nomogram was plotted and the slope was close to 1. The prognostic value of the nomogram was further validated in the validation cohort, with an AUC of 0.848 (95% CI: 0.819-0.877). Conclusions: A nomogram to predict ALNM was successfully established, especially for those who were of advanced age at diagnosis, had small tumor size, displayed low malignancy, and showed clinical ALN-negative, to avoid unnecessary axillary operation. The quality of life for patients is enhanced without conceding the overall survival rate.

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BACKGROUND: Sentinel lymph node biopsy (SLNB) and axillary lymph node dissection (ALND) may cause lymphatic and nervous system side effects in patients with breast cancer. It is imperative to develop a model to evaluate the risk of sentinel lymph node metastasis to avoid unnecessary operation. PATIENTS AND METHODS: A total of 2705 cases of female breast cancer patients enrolled in this retrospective study. We divided into the training group (SLNB group) and the validation group (ALND group) to analyze the relathionship between lymph node metastasis and clinical-pathological factors. Logistic regression analysis was performed to verify the variables which involved in ALN metastasis and established a prediction model. ROC curves were employed to evaluate the predictive ability of the model. RESULTS: In the SLNB group, 9 variables, including pathological type, histological grade, tumor size, hormone receptor, HER-2, Ki-67, multifocality, and molecular subtypes, were related to breast cancer ALN metastasis. Clinically negative lymph nodes, favorable histologic type, tumor size <2 cm, and Ki-67 <15% were at very low risk for lymph node metastasis. The AUC of the validation group was 0.786. CONCLUSION: We successfully establish a mathematics model to predict lymph node metastasis of breast cancer. Axillary surgery should be individual with preoperative clinical characteristics, especially for patients with a longer life expectancy.

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Nano-ZnO (nZnO) has been widely used as antibacterial, UV-shielding and photocatalysis materials, but limited by its contentious biosafety. In this paper, chitosan (CS) was introduced to enhance the biocompatibility. To solve the problem that nZnO reacts with the CS acid solution, alternate-feed spray drying was adopted to fabricate nZnO/CS composite microspheres. It was showed that nZnO remained the hexagonal phase, dispersed and embedded into CS microspheres. Based on the results of cytotoxicity and hemolysis test, biosafety was improved obviously. Further, the antibacterial activity of nZnO/CS was notably better than either of CS and nZnO individually. UV-shielding property and photocatalytic degradation test were estimated. In a word, alternate-feed spray drying presents a novel and cost-efficient method to fabricate multifunctional nZnO/CS microspheres with enhanced biosafety.

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