Nifuroxazide is an antidiarrheal medication that has promising anticancer activity against diverse types of tumors. The present study tested the anticancer activity of nifuroxazide against Ehrlich’s mammary carcinoma grown in vivo. Furthermore, we investigated the effect of nifuroxazide on IL-6/jak2/STAT3 signaling and the possible impact on tumor angiogenesis. The biological study was supported by molecular docking and bioinformatic predictions for the possible effect of nifuroxazide on this signaling pathway. Female albino mice were injected with Ehrlich carcinoma cells to produce Ehrlich’s solid tumors (ESTs). The experimental groups were as follows: EST control, EST + nifuroxazide (5 mg/kg), and EST + nifuroxazide (10 mg/kg). Nifuroxazide was found to reduce tumor masses (730.83 ± 73.19 and 381.42 ± 109.69 mg vs. 1099.5 ± 310.83) and lessen tumor pathologies. Furthermore, nifuroxazide downregulated IL-6, TNF-α, NFk-β, angiostatin, and Jak2 proteins, and it also reduced tumoral VEGF, as indicated by ELISA and immunohistochemical analysis. Furthermore, nifuroxazide dose-dependently downregulated STAT3 phosphorylation (60% and 30% reductions, respectively). Collectively, the current experiment shed light on the antitumor activity of nifuroxazide against mammary solid carcinoma grown in vivo. The antitumor activity was at least partly mediated by inhibition of IL-6/Jak2/STAT3 signaling that affected angiogenesis (low VEGF and high angiostatin) in the EST. Therefore, nifuroxazide might be a promising antitumor medication if appropriate human studies will be conducted.

Beta actin 1Beta actin 2 Beta actin 3 Beta actin 4 Supplementary 2. Figure containing the original Western blot gels for the measured proteins.

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Diffuse large B cell lymphoma (DLBCL) is a heterogeneous disease that displays a highly variable clinical outcome. It is a neoplasm of large transformed B cells with a diffuse growth pattern. DLBCL is the most common type of non-Hodgkin's lymphoma (NHL) (31% of all cases). Approximately half of patients with DLBCL are cured with current chemotherapy regimens. The purpose of this study was to evaluate BCl2 expression in 45 patients diagnosed with DLBCL of head and neck region and correlate the level of its immunohistochemical expression with different clinicopathological variables with emphasis upon patients' age, gender, nodal or extra-nodal location of lymphoma, patients' response to chemotherapy, progression-free survival (PFS) and overall survival (OS). A retrospective analysis of 45 patients diagnosed to have DLBCL. A cut off value of ≥ 50% protein expression denoted BCL2 positivity. Out of 45 cases, 36 cases (80%) revealed BCL2 positive expression and 9 cases (20%) were BCL2 negative. We found statistically significant differences in BCL2 expression regarding different patients' responses to chemotherapy, patients' OS and PFS (p ≤ 0.05). No statistically significant differences in BCL2 expression regarding the patients' Ann Arbor clinical stage, age group and tumor site (nodal or extra-nodal, p > 0.05) using the Chi-square test. BCL2 expression was analyzed in relation to 5 years OS and PFS using Kaplan Meier curves and Log Rank test for survival analysis. Cases that demonstrated BCL2 positivity revealed shortened OS and PFS with highly statistically significant differences among the studied variables (p = 0.000). We also found that patients who respond well to the chemotherapeutic regimen had negative BCL2 expression, the differences were statistically signifi-cant (p = 0.015). In conclusion, BCL2 expression could be considered a predictor for patients' chemotherapeutic response, OS and PFS.

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