Prediction of tumor metastasis via extracellular vesicles-treated platelet adhesion on a blood vessel chip.

In preclinical and clinical studies, it has been demonstrated that tumor-educated platelets play a critical role in tumorigenesis, cancer development, and metastasis. Unlike the role of cancer-derived chemokines in platelet activation, the role of cancer-derived extracellular vesicles (EVs) has remained elusive. Here, we found that interleukin-8 (IL-8) in cancer-derived EVs contributed to platelet activation by increasing P-selectin expression and ligand affinity, resulting in increased platelet adhesion on the human vessel-mimicking microfluidic system. Furthermore, platelet adhesion levels on vessels treated with human plasma-derived EVs demonstrated good discrimination between breast cancer patients with metastasis and those without, with the area under the curve (AUC) value of 0.88. While EpCAM expression on EVs could detect the existence of a tumor (AUC = 0.89), it performed poorly in predicting metastasis (AUC = 0.42). We believe that these findings shed light on the role of the interaction between cancer-derived EVs and platelets in pre-metastatic niche formation and tumor metastasis, potentially leading to the development of platelet-tumor interaction-based novel diagnostic and therapeutic strategies.

The Association of Estrogen Receptor Activity, Interferon Signaling, and MHC Class I Expression in Breast Cancer.

PURPOSE: The expression of major histocompatibility complex class I (MHC I) has previously been reported to be negatively associated with estrogen receptor (ER) expression. Furthermore, MHC I expression, level of tumor-infiltrating lymphocytes (TILs), and expression of interferon (IFN) mediator MxA are positively associated with one another in human breast cancers. This study aimed to investigate the mechanisms of association of MHC I with ER and IFN signaling. MATERIALS AND METHODS: The human leukocyte antigen (HLA)-ABC protein expression was analyzed in breast cancer cell lines. The expressions of HLA-A and MxA mRNAs were analyzed in MCF-7 cells in Gene Expression Omnibus (GEO) data. ER and HLA-ABC expressions, Ki-67 labeling index and TIL levels in tumor tissue were also analyzed in ER+/ human epidermal growth factor receptor 2 (HER2)- breast cancer patients who randomly received either neoadjuvant chemotherapy or estrogen modulator treatment followed by resection. RESULTS: HLA-ABC protein expression was decreased after ß-estradiol treatment or hESR-GFP transfection and increased after fulvestrant or IFN-γ treatment in cell lines. In GEO data, HLA-A and MxA expression was increased after ESR1 shRNA transfection. In patients, ER Allred score was significantly lower and the HLA-ABC expression, TIL levels, and Ki-67 were significantly higher in the estrogen modulator treated group than the chemotherapy treated group. CONCLUSION: MHC I expression and TIL levels might be affected by ER pathway modulation and IFN treatment. Further studies elucidating the mechanism of MHC I regulation could suggest a way to boost TIL influx in cancer in a clinical setting.

Intratympanic steroid injection for sudden sensorineural hearing loss: Impact of injection interval on therapeutic efficacy.

OBJECTIVE: To compare the effect of injection time intervals of intratympanic (IT) dexamethasone (DEX) in patients with idiopathic sudden sensorineural hearing loss (ISSNHL). METHODS: Seventy-five adults with ISSNHL were grouped into four groups according to the IT DEX interval. In addition to concurrent oral steroid medication for two weeks, patients received IT DEX injections every 1, 2, 3, and four days, respectively. (Group 1, Group 2, Group 3, and Group 4). We evaluated the treatment outcomes according to modified criteria from "Clinical Practice Guideline: Sudden Hearing Loss" of the American Academy of Otolaryngology-Head and Neck Surgery (AAOHNS) to justify treatment success. RESULTS: There were no significant differences in demographic and baseline audiometric data. The mean of pure tone audiometry (PTA) and speech discrimination score (SDSs) were significantly improved after oral steroid and IT DEX treatment in all four groups. Group 1 showed significantly higher improvement than Group 4 in PTA after treatment. There was a significantly higher complete recovery (CR) rate in Group 1 than Group 4. CONCLUSION: We found a statistically significant difference in the complete hearing recovery rate and audiometric results (PTA) between the group with a daily interval of injections and the group with a four-day time interval. Therefore, daily time intervals in intratympanic steroid injection may be considered as an option for better improvement of hearing in patients with ISSNHL.

Increased expression of ß amyloid precursor gene in the hippocampus of streptozotocin-induced diabetic mice with memory deficit and anxiety induction.

Diabetes has been associated with memory and behavioral dysfunctions such as anxiety. However, exact mechanisms of how diabetes affect such changes remain to be characterized. The purpose of present study is to search for streptozotocin-regulated genes in hippocampus of the mice using a differential display PCR technique, in the hope of type I diabetes-related hippocampal gene(s). It has been found that expression of a PCR product was increased by streptozotocin treatment and it was identified as ß amyloid precursor protein. These results were further confirmed by performing RT-PCR analysis. In addition, the protein expression of ß amyloid precursor protein as evidenced by Western blot analysis was increased in the hippocampus of streptozotocin-induced diabetic mice. To explore if the changes in amyloid ß precursor protein could be related with functional changes in the brain regarding memory activity and anxiety, passive avoidance test and elevated plus maze test were performed, respectively. There is significant reduction of memory formation and marked induction of anxiety in the streptozotocin-induced diabetic mice. These results suggest that increase of ß amyloid precursor protein may play a role in the memory loss and anxiety induction in type I diabetic mice.