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Abdelazim, S. A., O. G. Shaker, Y. A. H. Aly, and M. A. Senousy, "Uncovering serum placental-related non-coding RNAs as possible biomarkers of preeclampsia risk, onset and severity revealed MALAT-1, miR-363 and miR-17.", Scientific reports, vol. 12, issue 1, pp. 1249, 2022. Abstract

New predictors that could boost early detection of preeclampsia (PE) and prognosticate its severity are urgently needed. We examined serum miR-17, miR-363, MALAT-1 and HOTAIR as potential biomarkers of PE risk, onset and severity. This prospective study included 160 pregnant females; 82 PE cases and 78 healthy pregnancies. Serum samples were collected between 20 to 40 weeks of gestation. Early-onset PE was defined as developing clinical manifestations at ≤ 34 gestational weeks. Severe PE was defined as systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 110 mmHg and proteinuria (≥ 2 g/24 h or ≥ 2+ dipstick). Selection of PE-related non-coding RNAs and functional target gene analysis were conducted using bioinformatics analysis. Expression profiles were assessed by RT-qPCR. Serum miR-363 and MALAT-1 were downregulated, meanwhile miR-17 was upregulated, and HOTAIR was not significantly altered in PE compared with healthy pregnancies. miR-17 was elevated while miR-363 and MALAT-1 were reduced in severe versus mild PE. miR-363 was lower in early-onset versus late-onset PE. MALAT-1, miR-17 and miR-363 showed diagnostic potential and discriminated severe PE, whereas miR-363 distinguished early-onset PE in the receiver-operating-characteristic analysis. miR-363 and MALAT-1 were significantly associated with early and severe PE, respectively in multivariate logistic analysis. In PE, miR-17 and MALAT-1 were significantly correlated with gestational age (r = - 0.328 and r = 0.322, respectively) and albuminuria (r = 0.312, and r = - 0.35, respectively). We constructed the MALAT-1, miR-363, and miR-17-related protein-protein interaction networks linked to PE. Serum miR-17, miR-363 and MALAT-1 could have utility as new biomarkers of PE diagnosis. miR-363 may be associated with early-onset PE and MALAT-1 downregulation correlates with PE severity.

Sabri, A., M. Omran, S. Abdel Azim, R. Abdelfatah, and S. Shouman, "PB1919 EFFECT OF OCT1 GENE POLYMORPHISM ON RESPONSE TO IMATINIB MESYLATE IN CML PATIENTS", HemaSphere, vol. 3, issue S1, pp. 873, 2019. Abstract

Imatinib mesylate (IM) has been shown to be highly efficacious in the treatment of Chronic Myeloid Leukemia (CML). Continuous and adequate dosing is essential for optimal outcomes. There is a considerable variability in the level of molecular responses achieved with IM therapy. These differences could result from variable drug level which may be due to genetic factors.

The human organic cation transporter 1 (OCT1; SLC22A1) has been reported to be the main influx transporter responsible for active uptake of IM into CML cells.

We hypothesized that the SNPs of this gene could predict the outcomes of IM therapy in CML patients.

Fifty patients with CML at chronic phase were studied. All patients were monitored at outpatient clinic of the National Cancer Institute, Cairo University, Egypt. The study was approved by the NCI Ethical Committee for Clinical Research. Written Informed consent was obtained. The polymorphism of SLC22A1 gene was studied using PCR-RFLP technique. Imatinib mesylate level was determined using HPLC-massspectroscopy.

The mean IM trough plasma level in patients who achieved unfavorable response (n = 25) was 1019 ± 638 ng/mL, and in patients who achieved favorable response (n = 25) 1353 ± 611 ng/mL (p = 0.04).

In regard to SLC22A1 rs(628031) gene, heterogeneous & variant allele (GA&AA) was significantly correlated to unfavorable response while wild allele GG is linked to favorable response(p = 0.0006).

No significant correlation was detected between SLC22A1 gene polymorphism and drug level (p = 0.08).

Motawi, T. K., S. A. Abdelazim, H. A. Darwish, E. M. Elbaz, and S. A. Shouman, "Modulation of Tamoxifen Cytotoxicity by Caffeic Acid Phenethyl Ester in MCF-7 Breast Cancer Cells.", Oxidative medicine and cellular longevity, vol. 2016, pp. 3017108, 2016. Abstract

Although Tamoxifen (TAM) is one of the most widely used drugs in managing breast cancer, many women still relapse after long-term therapy. Caffeic acid phenethyl ester (CAPE) is a polyphenolic compound present in many medicinal plants and in propolis. The present study examined the effect of CAPE on TAM cytotoxicity in MCF-7 cells. MCF-7 cells were treated with different concentrations of TAM and/or CAPE for 48 h. This novel combination exerted synergistic cytotoxic effects against MCF-7 cells via induction of apoptotic machinery with activation of caspases and DNA fragmentation, along with downregulation of Bcl-2 and Beclin 1 expression levels. However, the mammalian microtubule-associated protein light chain LC 3-II level was unchanged. Vascular endothelial growth factor level was also decreased, whereas levels of glutathione and nitric oxide were increased. In conclusion, CAPE augmented TAM cytotoxicity via multiple mechanisms, providing a novel therapeutic approach for breast cancer treatment that can overcome resistance and lower toxicity. This effect provides a rationale for further investigation of this combination.

Motawi, T. K., S. A. Abdelazim, H. A. Darwish, E. M. Elbaz, and S. A. Shouman, "Could Caffeic Acid Phenethyl Ester Expand the Antitumor Effect of Tamoxifen in Breast Carcinoma?", Nutrition and cancer, pp. 1-11, 2016 Mar 23. Abstract

Despite tamoxifen (TAM) is beneficial in treating a significant proportion of patients with breast cancer, many women still relapse after long-term therapy. Caffeic acid phenethyl ester (CAPE) is a component of honeybee propolis, with a plethora of important biological actions including anticancer activity. This study aimed to explore the cytotoxicity, the type of drugs interaction as well as the apoptotic and autophagic pathways of the combined treatment of TAM and CAPE in MCF-7 cells. Their antitumor activity and effect on survival of mice bearing Ehrlich tumor were also analyzed. The results showed synergistic cytotoxic effects, manifested by significant activation of apoptotic machinery, along with downregulation of protein levels of Bcl-2 and beclin-1, upon using the combination regimen. However, the ratio between microtubule-associated protein light chain 3-II and -I was not altered. Moreover, a decrease in vascular endothelial growth factor level was detected. Similarly, TAM + CAPE increased the life span of tumor-bearing animals and caused a marked regression in their tumor size and weight compared with those treated with either TAM or CAPE alone. In conclusion, CAPE relatively improved the anticancer activity of TAM in both in vitro and in vivo models via its apoptotic and angiostatic potentials.

Abdelazeim, S. A., N. I. Shehata, Hanan Farouk Aly, and S. G. E. Shams, "Amelioration of oxidative stress-mediated apoptosis in copper oxide nanoparticles-induced liver injury in rats by potent antioxidants ", SCIENTIFIC REPORTS, vol. (2020)10:10812, pp. 14, 2020.