Co-Incidence of Epstein–Barr Virus and High-Risk Human Papillomaviruses in Cervical Cancer of Syrian Women

Epstein–Barr virus (EBV) has been recently shown to be co-present with high-risk human papillomaviruses (HPVs) in human cervical cancer; thus, these oncoviruses play an important role in the initiation and/or progression of this cancer. Accordingly, our group has recently viewed the presence and genotyping distribution of high-risk HPVs in cervical cancer in Syrian women; our data pointed out that HPVs are present in 42/44 samples (95%). Herein, we aim to explore the co-prevalence of EBV and high-risk HPVs in 44 cervical cancer tissues from Syrian women using polymerase chain reaction, immunohistochemistry, and tissue microarray analyses. We found that EBV and high-risk HPVs are co-present in 15/44 (34%) of the samples. However, none of the samples was exclusively EBV-positive. Additionally, we report that the co-expression of LMP1 and E6 genes of EBV and high-risk HPVs, respectively, is associated with poorly differentiated squamous cell carcinomas phenotype; this is accompanied by a strong and diffuse overexpression of Id-1 (93% positivity), which is an important regulator of cell invasion and metastasis. These data imply that EBV and HPVs are co-present in cervical cancer samples in the Middle East area including Syria and their co-presence is associated with a more aggressive cancer phenotype. Future investigations are needed to elucidate the exact role of EBV and HPVs cooperation in cervical carcinogenesis

HER-2/Epstein-Barr virus crosstalk in human gastric carcinogenesis: A novel concept of oncogene/oncovirus interaction.

Gastric cancer is the fourth most common cancer and the second leading cause of cancer deaths worldwide. Additionally, it is well-known that metastatic cancer disease is a major cause of morbidity and mortality in cancer patients. Several investigations reported that HER-2 (ErbB-2 receptor) and Epstein-Barr virus (EBV) are important etiological factors in human gastric cancer, where either oncogene/oncovirus alone can derive a major event of cancer progression and metastasis via epithelial-mesenchymal transition (EMT). Herein, we discuss, for the first time, the possibility of HER-2/EBV-oncoproteins interaction in human gastric cancer initiation and/or progression.Our research is supported by the College of Medicine and Qatar University

Elaeagnus Angustifolia Plant Extract inhibits Epithelial- mesenchymal Transition in Human Colorectal Cancer via β-catenin/JNK signaling Pathways

Elaeagnus angustifolia (EA) is a traditional plant that has been used as an alternative medicine for centuries. EA roles as anti-cancer has been investigated against different types of cancer, however, its effect against human cancer has not been investigated yet. Therefore, we investigated the aqueous EA extract effect on colorectal cancer (CRC) cell lines (HCT-116 and LoVo) and examined its underlying mechanisms of action in vitro. Our results showed that EA inhibited cell proliferation and disturbed cell-cycle progression of both CRC cell lines comparing to the control. Moreover, EA extract significantly reduced colony formation in addition to migration and invasion ability of both CRC cell lines this is confirmed by significant upregulation of E-cadherin and Pan-cadherin as well as down regulation of Vimentin. Further, β-catenin/JNK signaling pathway was analyzed and we found that EA extract significantly blocked the activity of total and phosphorylated β-catenin and JNK1/2/3.Scopu

Editorial: EBV-Associated Carcinomas: Presence, Role, and Prevention Strategies.

This special issue addresses an important topic related to the role of Epstein-Barr virus (EBV) in human carcinomas initiation and progression, which is one of the most common viral infections worldwide. Today, the relationship between EBV infection and several types of human lymphomas is clearly established, including Hodgkin and Burkitt's lymphoma; meanwhile, it was recently pointed out that EBV is present in nasopharyngeal carcinomas as well as other epithelial cancers (1). EBV is ubiquitous human herpesvirus 4, its genome codes more than 85 proteins of which only few are well-understood; More specifically, six nuclear antigens (EBNA: 1, 2, 3A, 3B, 3C, and LP); three latent membrane proteins/genes (LMP: 1, 2A, 2B) as well as small non-polyadenylated RNAs, EBERs 1 and 2 in addition to few microRNAs have been identified so far, as key regulators, of the oncogenic activity of this virus (2, 3). Present estimates indicate that EBV causes 200,000 new cancer cases annually, accounting for ~2% of cancers worldwide (Cancer Research UK). On the other hand, it is important to emphasize that recent investigations have revealed the possible involvement of EBV in other cancers such as cervical, gliomas, and breast, which are highlighted in this issue.This work is supported by Qatar University grants# GCC-2017-002 QU/KU and QUCG-CMED-20182019-3

Locking Src/Abl Tyrosine Kinase Activities Regulate Cell Differentiation and Invasion of Human Cervical Cancer Cells Expressing E6/E7 Oncoproteins of High-Risk HPV

In this study, we compared the effects of SKI-606 with Iressa, Src/Abl and EGF-R kinase inhibitors, respectively, on selected parameters in HeLa and SiHa cervical cancer cell lines, which express E6/E7 oncoproteins of high-risk HPV types 18 and 16, respectively. Our results show that SKI-606 and Iressa inhibit cell proliferation and provoke G0-G1 cell cycle arrest and reduction of S and G2-M phase using 2 and 5 μM concentrations of these inhibitors. In contrast, SKI-606 induces differentiation to an epithelial phenotype “mesenchymal-epithelial transition”; thus SKI-606 causes a dramatic decrease in cell motility and invasion abilities of HeLa and SiHa cancer cells, in comparison to untreated cells and Iressa-treated cells in which these parameters are only slightly affected. These changes are accompanied by a regulation of the expression patterns of E-cadherin and catenins. The molecular pathway analysis of Src/Abl inhibitor revealed that SKI-606 blocks the phosphorylation of β-catenin and consequently converts its role from a transcriptional regulator to a cell-cell adhesion molecule. Our findings indicate that SKI-606 inhibits signaling pathways involved in regulating tumor cell migration and invasion genes via β-catenin alteration, suggesting that Src inhibitor, in comparison to EGF-R, is a promising therapeutic agent for human cervical cancer

Fascin in Gynecological Cancers: An Update of the Literature

Fascin is an actin-binding protein that is encoded by the gene (located on chromosome 7). It triggers membrane projections and stimulates cell motility in cancer cells. Fascin overexpression has been described in different types of human cancers in which its expression correlated with tumor growth, migration, invasion, and metastasis. Moreover, overexpression of fascin was found in oncovirus-infected cells, such as human papillomaviruses (HPVs) and Epstein-Barr virus (EBV), disrupting the cell-cell adhesion and enhancing cancer progression. Based on these findings, several studies reported fascin as a potential biomarker and a therapeutic target in various cancers. This review provides a brief overview of the FSCN1 role in various cancers with emphasis on gynecological malignancies. We also discuss fascin interactions with other genes and oncoviruses through which it might induce cancer development and progression

Crosstalk between HER2 and PD-1/PD-L1 in Breast Cancer: From Clinical Applications to Mathematical Models.

Breast cancer is one of the major causes of mortality in women worldwide. The most aggressive breast cancer subtypes are human epidermal growth factor receptor-positive (HER2) and triple-negative breast cancers. Therapies targeting HER2 receptors have significantly improved HER2 breast cancer patient outcomes. However, several recent studies have pointed out the deficiency of existing treatment protocols in combatting disease relapse and improving response rates to treatment. Overriding the inherent actions of the immune system to detect and annihilate cancer via the immune checkpoint pathways is one of the important hallmarks of cancer. Thus, restoration of these pathways by various means of immunomodulation has shown beneficial effects in the management of various types of cancers, including breast. We herein review the recent progress in the management of HER2 breast cancer via HER2-targeted therapies, and its association with the programmed death receptor-1 (PD-1)/programmed death ligand-1 (PD-L1) axis. In order to link research in the areas of medicine and mathematics and point out specific opportunities for providing efficient theoretical analysis related to HER2 breast cancer management, we also review mathematical models pertaining to the dynamics of HER2 breast cancer and immune checkpoint inhibitors