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

High-Risk Human Papillomavirus and Colorectal Carcinogenesis

Colorectal, colon and rectal, cancer is the third most common malignancy in both men and women worldwide. Colorectal carcinogenesis is a complex, multistep process implicating environmental and lifestyle factors in addition to gene mutation and viral infections. On the other hand, it is well established that human papillomaviruses (HPVs) infection play a crucial role in certain types of human carcinomas including cervical and head and neck (HN); as roughly 96% and 30% of these cancers are positive for high-risk HPVs, respectively. Moreover, it has been reported that the presence of high-risk HPVs is associated with vascular invasion, lymph node metastases, and tumor size in cervical and HN cancers. Recently, several investigations pointed-out that high-risk HPVs are present in around 70% of human colorectal cancers. Likewise, our group has demonstrated that E6/E7 oncoproteins of HPV type 16 convert noninvasive and nonmetastatic human cancer cells to invasive and metastatic form. Accordingly, it is evident that high-risk HPVs are present in human colorectal cancers where they could play an important role in the development of these malignancies. In this chapter, we will discuss the presence and role of high-risk HPVs in human colorectal carcinogenesis and metastasis; particularly, the interaction between E5 and E6/E7 onco-proteins of high-risk HPVs in colorectal malignancies, which has been linked with the initiation and progression of these tumors

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

Human Papillomaviruses and Epstein-Barr Virus Interactions in Colorectal Cancer: A Brief Review.

Human papillomaviruses (HPVs) and the Epstein-Barr virus (EBV) are the most common oncoviruses, contributing to approximately 10%-15% of all malignancies. Oncoproteins of high-risk HPVs (E5 and E6/E7), as well as EBV (LMP1, LMP2A and EBNA1), play a principal role in the onset and progression of several human carcinomas, including head and neck, cervical and colorectal. Oncoproteins of high-risk HPVs and EBV can cooperate to initiate and/or enhance epithelial-mesenchymal transition (EMT) events, which represents one of the hallmarks of cancer progression and metastasis. Although the role of these oncoviruses in several cancers is well established, their role in the pathogenesis of colorectal cancer is still nascent. This review presents an overview of the most recent advances related to the presence and role of high-risk HPVs and EBV in colorectal cancer, with an emphasis on their cooperation in colorectal carcinogenesis

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

A comprehensive review on the antiviral activities of chalcones

Some viral outbreaks have plagued the world since antiquity, including the most recent COVID-19 pandemic. The continuous spread and emergence of new viral diseases have urged the discovery of novel treatment options that can overcome the limitations of currently marketed antiviral drugs. Chalcones are natural open chain flavonoids that are found in various plants and can be synthesised in labs. Several studies have shown that these small organic molecules exert a number of pharmacological activities, including antiviral, anti-inflammatory, antimicrobial and anticancer. The purpose of this review is to provide a summary of the antiviral activities of chalcones and their derivatives on a set of human viral infections and their potential for targeting the most recent COVID-19 disease. Accordingly, we herein review chalcones activities on the following human viruses: Middle East respiratory syndrome coronavirus, severe acute respiratory syndrome coronavirus, human immunodeficiency, influenza, human rhinovirus, herpes simplex, dengue, human cytomegalovirus, hepatitis B and C, Rift Valley fever and Venezuelan equine encephalitis. We hope that this review will pave the way for the design and development of potentially potent and broad-spectrum chalcone based antiviral drugs.Open Access funding provided by the Qatar National Library. Our lab is supported by grants from Qatar University: # QUCG-CPH-20/21-4, QUHI-CMED-19/20-1, QUCG-CMED-20/21-2.Scopu