Effects of rapamycin and AZD3463 combination on apoptosis, autophagy, and cell cycle for resistance control in breast cancer

sogutlu, fatma/0000-0002-1210-7660WOS:000600546400042PubMed: 33141044Breast cancer is the most common cancer in women and the leading cause of cancer mortality in women over 40 it's the year. The existence of the PI3K/AKT/mTOR pathway aberrations in more than 70% of breast cancer has caused to become a therapeutic target. AZD3463 is an anti-cancer agent used as a potential inhibitor of ALK/IGF1R. It also induces apoptosis and autophagy of the PI3K/AKT/mTOR pathway in cancer cells. Although the mTOR signaling might be inhibited by rapamycin treatment, signals transmitted from the upstream pathway supports cell survival and proliferation. The WST-1 assay test was performed to evaluate the anti-proliferative effects of rapamycin and AZD3463. Besides, the effects of them on apoptosis, autophagy, cytostatic, and metabolism in MCF7 breast cancer cells were investigated. Also, changes in the expression of apoptotic regulatory genes, cell cycle, and metabolism in the PI3K/AKT/mTOR Pathway were determined by Quantitative RT-PCR. The results showed that rapamycin and AZD3463 treatments significantly reduced survival in MCF7 cells. Also, apoptosis, autophagy, and cell population in the G0/G1 stage in the MCF7 cell category in the treatment group showed an increase compared to the control group. The combination of rapamycin and AZD3463 (AZD-RAPA) was determined as an additive according to isobologram analysis. in the combination of rapamycin with AZD3463, the expression of CDKN1B, PTEN, FOXO3, and APC genes increases, and the expression of PRKCB and PIK3CG genes decreases. Our results showed that the use of AZD-RAPA reduced the resistance of cancer cells to treatment and it leads cancer cells to apoptosis

Retinal vascular and structural recovery analysis by optical coherence tomography angiography after endoscopic decompression in sellar/parasellar tumors

Abstract We assessed the potential retinal microcirculation alterations for postoperative visual recovery in sellar/paraseller tumor patients with Optical Coherence Tomography Angiography (OCT-A). Two hundred ten eyes with sellar/parasellar tumor for which preoperative and postoperative (3 months) MRI Scans, Visual Acuity Test, Optical Coherence Tomography (OCT), OCT-A and, Visual Field Test data were available, besides 92 healthy eyes were evaluated. In the preoperative phase, significant reductions were observed in retinal vascular densities in various regions, including the Superficial Retinal Capillary Plexus (SRCP) (whole: p < 0.001, fovea: p = 0.025, parafovea: p < 0.001), Deep Retinal Capillary Plexus (DRCP) (whole: p < 0.001, fovea: p = 0.003, parafovea: p < 0.001), Peripapillary Vascular Density (PVD) (whole: p = 0.045, peripapillary: p < 0.001, nasal: p < 0.001, inferior: p < 0.001, temporal: p < 0.001), and Retinal Nerve Fiber Layer (RNFL) (nasal: p = 0.024, inferior: p < 0.001, temporal: p < 0.001, superior: p < 0.001) compared to the healthy control group. After surgery, the postoperative data of patients without chiasmal distortion were compared to their preoperative data. In the postoperative evaluation, significant increases were observed in vascular densities in patients without chiasmal distortion in the SRCP (whole: p < 0.001, parafovea: p = 0.045), DRCP (whole: p = 0.007, fovea: p = 0.006, parafovea: p = 0.040), PVD (peripapillary: p = 0.010, inferior: p < 0.001, temporal: p < 0.001, superior: p < 0.001), and RNFL (nasal: p = 0.011, inferior: p = 0.034, temporal: p = 0.046, superior: p = 0.011). Furthermore, significant associations were observed in the ROC analysis between the postoperative Visual Field Mean Deviation (VFMD) and SRCP (whole AUC = 0.793, p < 0.001, cut-off = 51.45, parafovea AUC = 0.820, p < 0.001, cut-off = 53.95), DRCP (whole AUC = 0.818, p < 0.001, cut-off = 55.95, parafovea AUC = 0.820, p < 0.001, cut-off = 59.05), PVD (temporal AUC = 0.692, p < 0.001, cut-off = 55.10), and RNFL (whole AUC = 0.690, p = 0.001, cut-off = 119.5, inferior AUC = 0.712, p < 0.001, cut-off = 144.75). These findings indicate a potential role of pre and post-operative OCT-A measurements in the assessment of surgical timing and postoperative visual recovery in patients with or without optic chiasm distortion

The acute and long term effects of acupuncture on heart rate variability

236-239In a recent study, the possible effect of acupuncture in modulating heart rate variability (HRV) in both healthy and non-healthy subjects were reported, while previous review reported that acupuncture did not have any convincing effect on HRV in healthy subjects. We aimed to reinvestigate the possible helpful effect of acupuncture on HRV parameters and to test the possible differences between acute and long term (20 minutes) acupuncture applications. Twenty nine female subjects were participated in this study. For the acupuncture therapy, HT 7 acupuncture point (shen men) was selected. Acupuncture needle was placed for 1 minute in acute acupuncture application and 20 minutes in long term acupuncture. The recording ECG (HRV) was applied before and after acute and long term acupuncture therapies. Almost all HRV parameters increased after the acute acupuncture and some HRV parameters after the long term acupuncture compared to before therapy in healthy persons. There were no differences between acute and long term applications. These results indicate that acupuncture might be cardio protective and might restore sympathovagal imbalances by stimulating the peripheral nervous system. Also, the long term acupuncture application is not essential for the cardio protective effect