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"n Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso-bidi-theme-font:minor-bidi;} Background: Human respiratory syncytial virus (HRSV) is the most important viral agent of acute lower respiratory tract disease in infants and young children worldwide. This virus is responsible for 50% brochiolitis and 25% pneumonia in infants. There are limited data of molecular epidemiology of HRSV from developing countries. This is the report on the molecular epidemiology of human respiratory syncytial virus in Iran."n"nMethods: In this study, RT-PCR for second hypervariable region of the HRSV G glycoprotein was performed on 72 throat swabs collected from children less than 5 years of age with acute respiratory symptoms in 1386."n"nResults: Of the 72 throat swabs collected from children with acute respiratory symptoms, 14 (19.44%) were positive for HRSV. Phylogenetic analysis revealed that all HRSV-positive samples clustered in three genotypes of subgroup A: 12 strains (85/71%) in genotype GA2, 1 strain (7/1%) in genotype GA1, and 1 strain (7/1%) in genotype GA5. In this study we couldn't identify any genotype of subgroup B."n"nConclusion: Our results revealed that multiple genotypes of subgroup A were co-circulated during 1386 in children less than 5 years of age in Iran. Also this study revealed that genotype GA2 was predominant genotype in isolates were obtained from several cities (Tehran, Isfahan, Karaj, Qazvin, Bandar Abbas, Shahreza), so we speculate that this genotype may be predominant during 1386 in Iran. This study supported that RT-PCR for second variable region of G protein is an effective method for further studies of HRSV genotype designation in Iran.

Despite advancements in science, researchers still face challenges in curing patients with malignancies. This health issue is linked to various risk factors, including alcohol consumption, age, sex, and infectious diseases. Among these, viral agents play a significant role in cancer-related health problems and are currently a subject of ongoing research. In this review, we summarize how several viruses-such as herpesviruses, human papillomavirus, hepatitis B virus, hepatitis C virus, and adenovirus-impact cancer signaling pathways through their effects on the tumor suppressor PTEN., Competing Interests: Declaration of Competing Interest There is no conflict, (Copyright © 2024. Published by Elsevier GmbH.)

Some human cancers worldwide may be related to human tumor viruses. Knowing, controlling, and managing the viruses that cause cancers remain a problem. Also, tumor viruses use ubiquitin-proteasome system (UPS) that can alter host cellular processes through UPS. Human tumor viruses cause persistent infections, due to their ability to infect their host cells without killing them. Tumor viruses such as Epstein-Barr virus, hepatitis C virus, hepatitis B virus, human papillomaviruses, human T cell leukemia virus, Kaposi's sarcoma-associated herpesvirus, and Merkel cell polyomavirus are associated with human malignancies. They interfere with the regulation of cell cycle and control of apoptosis, which are important for cellular functions. These viral oncoproteins bind directly or indirectly to the components of UPS, modifying cellular pathways and suppressor proteins like p53 and pRb. They can also cause progression of malignancy. In this review, we focused on how viral oncoproteins bind to the components of the UPS and how these interactions induce the degradation of cellular proteins for their survival., Competing Interests: Conflict of Interest None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. ( https://creativecommons.org/licenses/by/4.0/ ).)

Background: Both internal and external risk factors can accelerate the progression of breast cancer which is the reason why clinicians have tried to find new biomarkers for this health problem. Human endogenous retrovirus-W (HERV-W) can be one of these biomarkers, as it has been mentioned that some genes of this virus are able to have either higher or lower expression in numerous cancerous cells. In this study, we aimed to compare HERV-W envelope expression in breast cancer tissues and normal ones since its effects on this malignancy have not been clear., Materials and Methods: We collected 46 breast cancer tissues and their normal adjacent ones. After extracting the RNA of breast samples, we evaluated the expression of HERV-W envelope syncytin-1 and 2 using quantitative real-time polymerase chain reaction (PCR) in different kinds of breast cancer stages., Results: Data showed that more than 13% of patients had a family history of breast cancer; moreover, approximately half of the tissues were estrogen receptor or progesterone receptor positive. Lymph node metastasis was seen in 52% of the patients, and about 40% of tumors were larger than 2 cm. Real-time PCR showed that syncytin-1 and 2 had upward regulation with (* P < 0.05) and (** P < 0.01), respectively., Conclusion: As the expression of HERV-W Env (syncytin-1, syncytin-2) was higher in breast cancerous tissues in comparison with normal ones, we believe that these genes may have a role to play in monitoring patients suffering from this type of cancer. However, further studies are needed to confirm this hypothesis., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Research in Medical Sciences.)

The role of numerous risk factors, including consumption of alcohol, smoking, having diet high in fat and sugar and many other items, on caner progression cannot be denied. Viral diseases are one these factors, and they can initiate some signalling pathways causing cancer. For example, they can be effective on providing oxygen and nutrients by inducing VEGF expression. In this review article, we summarised the mechanisms of angiogenesis and VEGF expression in cancerous tissues which are infected with oncoviruses (Epstein-Barr virus, Human papillomavirus infection, Human T-lymphotropic virus, Kaposi's sarcoma-associated herpesvirus, Hepatitis B and hepatitis C virus)., (© 2023 John Wiley & Sons Ltd.)

Background: Breast cancer is the second type of cancer in the world. Some internal and external risk factors, especially infection diseases, can progress breast cancer. As the relation between varicella zoster virus (VZV), human papillomavirus (HPV), herpes simplex virus type 2 (HSV-2), and breast cancer has not been understood, it was attempting to find the effect of these viruses and breast cancer in this study., Materials and Methods: We collected 40 breast cancer and 50 healthy adjacent tissues from Taleghani and Imam Hossein Hospital, Tehran, Iran, in 3 years starting in 2017. After extracting DNA from breast tissues, multiplex polymerase chain reaction (PCR), nested PCR, and PCR were done to analyze the prevalence of HSV-2, VZV, and HPV., Results: Our results showed that HPV may be one of the important causes of breast cancer. Nested PCR illustrated nine breast cancerous tissues (mean age: 43) and three healthy adjacent ones (mean age: 41) were infected by HPV. Phylogenetic analysis illustrated that all of the infected HPV cancerous and healthy tissues were HPV 18 (except two healthy samples infected with HPV 6). Nevertheless, there were not any infected tissues by HSV-2 and VZV., Conclusion: It seems that HPV virus type 18 can have high prevalence in breast cancerous tissues in comparison with healthy adjacent ones, and it is likely to have an effect on breast cancer progression. However, the opposite trend is true for HSV-2 and VZV as we did not find any differences between different kinds of breast tissues., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Journal of Research in Medical Sciences.)

Background and Objectives: Breast cancer is currently the most commonly diagnosed neoplasm in women worldwide. There is evidence that human papillomavirus (HPV) infection may play a key role in breast cancer aggressiveness, but results are conflicting across studies. The aim of this study was to investigate the presence of the HPV viral genome in benign and malignant breast tissue samples and its clinicopathological characteristics of cancer., Materials and Methods: In this case-control study, 100 formalin-fixed paraffin-embedded (FFPE) of breast cancer and 100 blocks of non-cancerous breast tissue were selected as a control group from the pathology department of Imam Khomeini Hospital in Ahvaz from 2020-2022. The presence of HPV was detected using nested PCR including MY09/11 primers and sequencing were performed for virus genotyping., Results: The present study enrolled 100 subjects each in two cancer and control groups with a mean age of 52.81±13.23 and 35.77±11.65, respectively. The risk of cancer in HPV-infected patients is almost 5 times higher than in HPV-negative individuals, it is not statistically significant (OR =4.99, 95% CI 0.35 to 72.15, p=0.238). The prevalence of HPV in the cancer and control groups was 7% and 1%, respectively and HPVs detected in two groups were of the HPV 16 genotype. Although the chance of ER and PR expression, lymphvascular involvement, perineural invasion, and higher tumor grade was higher in HPV-positive subjects than in HPV-negative subjects, this was not statistically significant (OR>1, p>0.05)., Conclusion: Based on studies reporting the existence of sequences of different high-risk HPV types (oncogenes) in breast cancer tissues, this study confirmed the hypothesis of a possible infectious cause in the development of breast cancer. So far, however, the results have been controversial and inconclusive. Further studies with large sample sizes are needed to demonstrate the link between HPV and breast cancer., (Copyright © 2023 The Authors. Published by Tehran University of Medical Sciences.)

Background: Scientists have believed that a number of risk factors, especially viral infectious agents, can be related to respiratory diseases. Due to the pandemics in 2019, Human Respiratory Syncytial Virus and Coronavirus have attracted the attention of different kinds of research. In this study, we attempted to evaluate the prevalence of these viruses., Materials and Methods: After extracting the RNA and DNA of these viruses, molecular tests were employed to report the rate of them in patients suffering from respiratory symptoms., Results: Our results demonstrated that 31 samples were COVID-19 positive. Furthermore, two cases had Respiratory syncytial virus (RSV) subgroup A infections. However, no cases showed a coinfection of both viruses., Conclusions: It seems that during the pandemic of COVID-19 , RSV should not be ignored as it can be responsible for the respiratory syndrome., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Advanced Biomedical Research.)

Background: Encephalitis is an uncommon, serious brain infection that can cause fatality among children. The cause of most encephalitis remained unknown, yet viruses are the most well-known infectious agents that cause encephalitis. This study aimed to determine varicella-zoster virus (VZV) and herpes simplex virus type 1, 2 (HSV1/2) among individuals who are under 5 years of age in Iran., Materials and Methods: In this study, 149 cerebrospinal fluid samples of suspected patients of encephalitis were analyzed with some symptoms, such as seizure, fever, nausea loss of consciousness, and dizziness from Mofid Children's Hospital in Tehran, Iran. Then, the molecular evaluation of samples was performed using multiplex Polymerase Chain Reaction (PCR) for detecting HSV1/2 and VZV., Results: The mean age of the patients was 1.8 years. Also, 63.4% of children were male and 36.6% were female. Out of 149 tested samples, 11 (7.3%) showed the viral DNA for one of the herpes viruses (7.3%). Nine samples were HSV1 positive (6.0%) and two samples were VZV positive (1.3%). Fever and vomiting were the most frequent symptoms. The mean ± standard deviation (SD) WBC and counts in cerebrospinal fluid (CSF)-positive samples, and all included samples were 298.8 ± 552.7 cells/μL and 131.1 ± 474.6 cells/μL, respectively., Conclusions: Although viral encephalitis is considered a threat to children's health, with accurate diagnosis and appropriate antiviral drugs, death and neurological complications in children can be prevented., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Advanced Biomedical Research.)

Background: In the current age of diagnostic approaches in cancer, countless efforts have been allocated to identify novel and efficient biomarkers to detect cancer in its early stages. We focused on evaluating the correlation between the progression of gastrointestinal cancer, a leading cause of cancer death worldwide, and human endogenous retrovirus (HERV)., Materials and Methods: In this study, we conducted a study on the peripheral blood mononuclear cells (PBMC) gathered from gastric and colon cancer patients. We focused on HERV-K rec, np9, gag expression analysis by quantitative real-time PCR, after extraction of RNA and synthesizing cDNA., Results: Unlike np9 whose expression increased significantly in the colon and gastric cancers, the mRNA level of the rec gene declined in both cancers. Moreover, our data illustrated that the over-expression of the gag gene was only observed in colon cancerous cells rather than gastric malignancy., Conclusions: Overall, given the correlation between the expression level of HERV-associated genes and gastrointestinal cancer, our study suggests that these genes could be considered beneficial markers for cancer diagnosis. However, researchers should conduct studies in future articles on whether these genes can be employed as biomarkers in gastrointestinal cancer., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Advanced Biomedical Research.)

Background: Head and neck squamous cell carcinoma is one of the most important malignancies, worldwide. Oncogenic viruses, such as human papilloma virus (HPV) and Epstein-Barr virus (EBV), are linked to these cancers and studies suggest a possible interaction between HPV and EBV during co-infections to promote oncogenesis. Nonetheless, these reports are controversial and demand more investigations in this regard. The present work to assessed the prevalence of HPV and co-infection with EBV in oral and oropharyngeal squamous cell carcinomas., Methods: Formalin-fixed paraffin-embedded tissues were collected from 166 archived oral and oropharyngeal squamous cell carcinoma samples from Ahvaz Imam Khomeini hospital, Ahvaz, Iran, from March 2013 and December 2019. Nested-PCR was used to detect the viruses and type-specific PCR/nested-PCR and sequencing were performed for virus genotyping., Results: Out of the 166 specimens, 84.33% and 16.42% were from oral cavity and oropharynx, respectively; of which, 32 cases (19.3%) were HPV-positive (16.42% of oral cavity and 34.6% of oropharynx). HPV was detected in 36.36%, 25%, and 16.42% of base of tongue, tonsil, and oral tongue tumors, respectively. HPV was more associated with well differentiated tumors (24;18.04%) in compared to moderately and poorly differentiated ones. Regarding HPV-16 genotyping, 7 (21.8%) out of the 32 samples were found to be HPV-16 (4/26 (15.38%) for oropharynx and 3/140 (2.14%) for oral cavity). Moreover, 90 samples were evaluated for EBV infection and co-infection; of which, 4 (4.4%) subjects tested positive for EBV, including two cases with HPV co-infection. All the positive cases were EBV type B, from oral cavity, and histologically well differentiated., Conclusions: HPV was more associated with oropharyngeal cancer. This association has been linked to various factors such as repeated oral and oropharyngeal exposure to HPV due to change in patterns of sexual behaviors; a phenomenon that may demand routine HPV vaccination.

Background: The Herpesviridae family plays a significant etiological role in central nervous system viral infections during primary infection or reactivation from a latent form. Early detection is crucial because prescribing some antivirals can prevent severe side effects or life-threatening conditions., Methods: In this study, 251 CSF specimens were collected from patients with clinical suspicion of viral encephalitis in Pars Hospital, Tehran, Iran. DNA was extracted, and a multiplex PCR was designed to investigate the presence of herpes simplex virus-1, herpes simplex virus-2, varicella zoster virus, Epstein-Barr virus, and cytomegalovirus., Results: Overall, 59 cases of the 251 CSF samples were positive for multiplex PCR (23.5%). The most frequent positive findings were EBV and HSV, with a prevalence of 10.3% and 8.7% (5.5% HSV-1 and 3.1% HSV-2), respectively. Four co-infections were also seen in this study., Conclusions: This multiplex PCR assay detects simultaneously different herpesviruses in CSF samples of patients with suspected encephalitis in 2 rounds of PCR amplification; therefore, it is a reliable and cost-saving diagnostic method for evaluating patients infected with herpesvirus with neurological disorders., (© 2021 S. Karger AG, Basel.)

In this study, we focused on the emergence of extensively drug-resistant (XDR), pandrug-resistant (PDR), and hypervirulent Klebsiella pneumoniae (hvKP) in Iran. During 2018 to 2020 a total of 52 K. pneumoniae isolates were collected from different clinical specimens. The hvKP isolates were identified by PCR amplification of virulence and capsular serotype-specific genes. Hypermucoviscous K. pneumoniae (hmKP) were identified by string test. Carbapenem-resistant hvKP (CR-hvKP), multidrug-resistant hvKP (MDR-hvKP), extensively drug-resistant hvKP (XDR-hvKP), and pandrug-resistant hvKP (PDR-hvKP) were determined by disc diffusion method, Carba-NP test and PCR method. XDR-hvKP isolates were typed by multilocus sequence typing (MLST). Among all K. pneumoniae isolates 14 (26.9%) were identified as hvKP and 78.6% (11/14) of them were hmKP however, none of the classic K. pneumoniae (cKP) isolates were hmKP. The predominant capsular serotype of hvKP was K2 (42.85%) followed by K1 (35.71%). The prevalence of MDR-hvKP, XDR-hvKP and PDR-hvKP isolates were 6 (42.9%), 5 (35.7%) and 1 (7.1%), respectively. ESBL production was found in 85.7% of hvKP isolates and most of them carried bla TEM gene (78.6%) and 6 isolates (42.9%) were CR-hvKP. Among hvKP isolates, 1 (7.1%), 2 (14.3%), 3 (21.4%), 8 (28.6%), and 11 (78.6%) carried bla NDM-6, bla OXA-48, bla CTX-M, bla SHV, and bla TEM genes, respectively. According to MLST analysis, 2, 1, 1, and 1 XDR-hvKP isolates belonged to ST15, ST377, ST442, and ST147, respectively. The occurrence of such isolates is deeply concerning due to the combination of hypervirulence and extensively drug-resistance or pandrug-resistance.

There are a number of risk factors, especially viral diseases, which can lead to infertility. Among the various viral infections, much attention has been given to the role of the Papillomaviridae and Herpesviridae. After collecting 82 semen samples (37 teratospermia, 2 asthenozoospermia, 2 oligoasthenospermia, 1 oligospermia, 6 asthenoteratospermia and 34 normal semen samples), and washing them, the DNA from both freshly ejaculated spermatozoon and washed spermatozoa was extracted. Subsequently, the prevalence of EBV, CMV, HSV-1, HSV-2, VZV and HPV was evaluated using Multiplex PCR and Nested PCR. In this study, 1 normal and 5 abnormal semen samples were infected with HSV-1 (1 normal, 4 teratospermia and 1 oligoasthenospermia). In addition, there were 2 VZV-positive samples (both were teratozoospermia). Nested PCR indicated that 1 asthenozoospermia, 1 asthenoteratospermia, 3 teratospermia and 4 normal samples were HPV positive (including 8 HPV-18 and 1 HPV-33). Among 9 HPV-positive subjects, 3 samples were negative after washing the infected samples. The prevalence of EBV, CMV, VZV, HSV-1 and HSV-2 remained unchanged prior to and after washing. Maybe sperm washing can be useful to eliminate HPV infection from semen samples, but further investigation is required because of the small number of samples., (© 2021 Wiley-VCH GmbH.)

Background: Despite medical advances, central nervous system (CNS) diseases put a pressure on the health care system. A number of risk factors, especially infectious agents can accelerate the progression of meningitis. As viruses probably account for most cases of meningitis, the diagnosis of them can reduce antibiotic prescriptions. Among various types of infectious diseases, the relationship between two important virus families, including Picornaviridae and Herpesviridae, and meningitis has attracted attraction., Methods: In this study, one hundred and two samples were collected from patients who experienced symptoms, such as the loss of consciousness, seizures, muscle weakness, fever, headache, rash, and severe dementia, between November 2018 and September 2019. After RNA and DNA extraction, the prevalence of Enterovirus (EV), Cytomegalovirus (CMV), Epstein-Barr virus (EBV), Herpes simplex virus type 1 (HSV-1), Herpes simplex virus type 2 (HSV-2), and Varicella zoster virus (VZV) was evaluated using PCR, multiplex PCR, and nested PCR., Results: Results indicated that there were two VZV DNA-positive specimens, while six and five samples were infected with HSV-1 and EBV, respectively., Conclusion: We reported that the prevalence of EBV, HSV-1, and VZV in patients, suffering from meningitis cannot be ignored; however, further investigation is needed., (© 2021 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

Background: The role of viruses as a cause of breast cancer (BC) has been significantly investigated in recent years. Human papillomavirus (HPV) has been detected in invasive breast carcinomas, while most studies have only focused on the detection of viral DNA, we aimed to examine the prevalence and genotypes of HPV among Iranian BC patients. We also examined the presence of herpes simplex-1 (HSV-1), herpes simplex-2 (HSV-2), varicella zoster virus (VZV), and cytomegalovirus (CMV) in these samples., Methods: We collected and analyzed 70 Formalin-Fixed Paraffin-Embedded (FFPE) blocks including 59 BC samples, and 11 benign breast lesions as control from Iranian patients using nested PCR. Real-time PCR utilized as a confirming test to nested PCR findings. Genotyping of HPV positive samples was performed, the samples were also subjected to a multiplex PCR to detect HSV-1, HSV-2, VZV, and CMV in BC., Results: Papillomavirus DNA was present in 7 of 59 BC samples (11.8%); while none was detected in control samples. The most prevalent type was HPV18, followed by HPV 6. All HPV positive patients had high tumor grades (II/ III) with a histologic diagnosis of ductal carcinoma. The patient age range was 33 to 73 years with a median of 51 years. Most of HPV positive patients had low levels of education. HPV16 was not detected. Also, 5 of 59 BC specimens (8.47%), were positive for HSV-1. But none of the samples were positive for HSV-2, VZV, and CMV., Conclusions: Our results suggest a carcinogenesis role for High-risk HPV (HPV18) in breast tumors. Our findings of HSV-1 and low-risk HPV (HPV6) in BCs may propose a cancer-causing role for them. Further large-scale studies are warranted to assess the significance of our findings.

Background and Aim: Colorectal Cancer (CRC) is one of the most frequent cancers diagnosed in both men and women worldwide. Fusobacterium nucleatum adhesin A (FadA) has an important potential factor in the development or progression of CRC. The aim of the present study was to evaluate the proliferative effect of recombinant FadA on SW480 colorectal cancer cell line., Materials and Methods: The recombinant pET21(b)-fadA plasmid was synthesized and transformed into competent E.coli DH5α. In the next step, induction and expression of recombinant FadA were carried out in E. coli BL21 (DE3) competent cells. Expression and purification of protein were successfully done and it was analyzed and confirmed by SDS-PAGE and western blotting. The proliferative effect of purified FadA on SW480 CRC cell line was evaluated using MTT assay and cell counting methods., Results: Visualization of the specific band isolated from the linear plasmid on the agarose gel confirmed the presence of the desired gene. After electrophoresis and Coomassie blue staining, the protein of interest with an approximate molecular weight of 13KDa was detected. The MTT assay, similar to cell counting methods, revealed that FadA dose and time-dependently promoted SW480 cell growth and proliferation in 24, 48 and 72 hours., Conclusion: The results showed that FadA stimulates proliferation of SW480 colorectal cancer cell line with a dose and time-dependent manner., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Cancer is a leading public health issue that accounts for million deaths around the world every year. Human cancers contain over 100 types, which are categorized into different groups. Adenocarcinoma is one of those categories of cancer that begins from the glans and involves various tissues such as lung, esophagus, pancreas, prostate and colorectal. A range of risk factors has been identified for the development and progression of adenocarcinomas. One of these risk factors are viruses that serves special mechanisms to affect important host cell factors and tumorigenic pathways, contributing in development and promotion of adenocarcinomas. Here, we summarized the main viruses and their mechanisms implicated in the course of various adenocarcinomas development., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Molecular profiling techniques are the rapid detection of biomarkers in the human papillomavirus (HPV) infected cells. We aimed to measure the expression level of three cell factors including Snail1, ZEB-1, and E-cadherin in cervical cancer (CC), precancerous and healthy samples, simultaneously, to find potential biomarkers., Methods: The expression level of the mentioned cell factors were investigated in 72 CC patients, precancerous patients, and healthy controls by using Real-Time PCR., Results: The results demonstrated a significant reduction in the expression level of E-cadherin in cancer and precancerous cases than that in healthy cases; whereas the expression level of ZEB-1 and Snail1 were upregulated in cancer and precancerous samples. The receiver operating characteristic (ROC) analyses shows the highest AUC value emerged for Snail1: 1(95% CI: 1-1) in comparing CC and healthy groups with a sensitivity of 100.0 % and specificity of 100.0%., Conclusion: The molecular biomarker Snail1 may be helpful to early diagnosis and prognosis of CC in the HPV-infected human populations. Considering the increased expression level of Snail1 in cancer and precancerous tissue compared to healthy tissue as well as the area under the ROC curve, Snail1 can be used for early detection of CC., Competing Interests: Conflict of interest The authors declare that there is no conflict of interest., (Copyright © 2020 Farzanehpour et al. Published by Tehran University of Medical Sciences.)

Programmed death ligand 1 (PD-L1) is a surface glycoprotein that induces T-cell anergy or apoptosis by binding to PD-1 on activated T and B cells. It is also known as a cluster of differentiation 274 (CD274) or B7 homolog 1 (B7-H1). Suppressing the adaptive arm of the immune system is the critical role of PD-L1.so it prohibits the proliferation of activated T cells and reduces apoptosis in regulatory T cells. When PD-L1 binds to PD-1, it prevents T cells from killing other cells such as cancer cells. Viruses have various strategies to evade from the immune system such as modifying host gene expression or deregulating proteins function. So they can directly or indirectly change the expression of PD-L1. This study proposed to evaluate the effect of viruses on the expression of PD-L1 which leading to uncontrolled cell growth and tumor formation. We have studied serious tumorigenic viruses, including Human Papillomaviruses (HPV), Epstein-Barr viruses (EBV), Human T-cell leukemia viruses type 1 (HTLV-1), Hepatitis B viruses (HBV) and Hepatitis C viruses (HCV). So we surveyed the correlation between the presence of viruses and expression of PD-L1. Most studies showed the PD-L1 overexpression due to viral functions; however, further studies are needed to better understand the role of the PD-1/PD-L1 pathway in virus-associated cancers as a candidate of anti- PD-L1 therapy., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The role of several risk factors, such as pollution, consumption of alcohol, age, sex and obesity in cancer progression is undeniable. Human malignancies are mainly characterized by deregulation of cyclin-dependent kinases (CDK) and cyclin inhibitor kinases (CIK) activities. Viruses express some onco-proteins which could interfere with CDK and CIKs function, and induce some signals to replicate their genome into host's cells. By reviewing some studies about the function of CDK and CIKs in cells infected with oncoviruses, such as HPV, HTLV, HERV, EBV, KSHV, HBV and HCV, we reviewed the mechanisms of different onco-proteins which could deregulate the cell cycle proteins., Competing Interests: Competing interestsThe authors declare no conflicts of interests., (© The Author(s) 2020.)

Objective: It has been indicated that there is a tight association between cancer and different factors, such as environment and genetics, including aberrantly expressed microRNAs. The crucial role of microRNAs in the regulation of diverse signaling pathways in gastrointestinal cancer has been established in several studies. In this study, we aimed to evaluate the expression of microRNA-9 and -192 in colon and gastric cancers. After extracting the RNA from tissues and serum samples of patients, suffering from colon and gastric cancer, cDNA was synthesized. Then by performing quantitative real-time PCR, we evaluated the expression level of miR-9-5p and miR-192-5p in collected samples., Results: Unlike to colon cancer in which the expression level of miR-9-5p remained unchanged, the relative expression of this miRNA decreased remarkably in gastric cancer (with P value < 0.05), in comparison with normal adjacent tissues. In agreement with this finding, we also found that the expression level of miR-192-5p was decreased in gastric cancer tissues, compared to normal gastric tissue. Given the reduction in the expression level of miR-9-5p and miR-192-5p in gastric cancer, it could be postulated to consider these miRNAs as promising diagnostic biomarkers.

Human cytomegalovirus (CMV), an opportunistic pathogen belonging to Herpesviridae family, is considered as one of the major causes of morbidity and mortality among wide variety of patients, particularly in transplant recipients and HIV positive patients. As this virus can be resistant to treatment, frequency of CMV in patients who receive organ transplantation and people suffering from AIDS was studied between 1980 and 2019. Medline (via PubMed), Embase, Web of Science, and the Iranian Database were reviewed, and Comprehensive Meta-Analysis (V2.0, Biostat) software analyzed all data. Finally, we used Cochran's Q-statistic to encounter heterogeneity between different studies. Meta-analyses indicated, GCV resistance was 14.1% (95% CI 11.2-17.7); however, in patients suffering from AIDS and organ transplantation were 19.5% (95% CI 14.7-25.4) and 11.4% (95% CI 8.1-15.8), respectively. There were increasing rates in the prevalence of GCV resistance in CMV among transplant recipients, and HIV positive patients. Therefore, evaluation of these refractory infections is beneficial., Competing Interests: Declaration of competing interest The authors declare no conflicts of interests., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Toxin-antitoxin (TA) systems are two-component genetic modules widespread in bacterial and archaeal genomes, in which the toxin module is rendered inactive under resting conditions by its antitoxin counterpart. Under stress conditions, however, the antitoxin is degraded, freeing the toxin to exert its lethal effects. Although not evolved to function in eukaryotes, some studies have established the lethal activity of these bacterial toxins by inducing apoptosis in mammalian cells, an effect that can be neutralized by its cognate antitoxin. Inspired by the way the toxin can become active in eukaryotes cells, we produced an engrained yoeB-yefM TA system to selectively kill human breast cancer cells expressing a high level of miR-21. Accordingly, we generated an engineered yefM antitoxin gene with eight miR-21 target sites placed in its 3'untranslated region. The resulting TA system acts autonomously in human cells, distinguishing those that overexpress miR-21, killed by YoeB, from those that do not, remaining protected by YefM. Thus, we indicated that microRNA-control of the antitoxin protein of bacterial TA systems constitutes a novel strategy to enhance the selective killing of human cancer cells by the toxin module. The present study provides significant insights for developing novel anticancer strategies avoiding off-target effects, a challenge that has been pursued by many investigators over the years., (© 2019 Wiley Periodicals, Inc.)

Background: High-risk (HR) Human papillomaviruses (HPVs) are known as the main factors implicated in the pathogenesis of cervical preinvasive and invasive lesions. Therefore, the presence or absence of HR-HPV can be followed for the prognosis of low-grade and high-grade squamous intraepithelial lesions. Since the overexpression of p16INK4a protein depends on the presence of transcriptionally-active HPV, and due to its availability and simple interpretation, it may be considered as a proper marker to diagnose cervical cancer., Methods: An immunohistochemical analysis of p16INK4a was performed in 72 cervical tissue specimens at Imam Khomeini Complex Hospital (Tehran, Iran) from 2016 to 2018. The performance parameters were calculated and compared using receiving operating characteristics curve (ROC) details., Results: p16INK4a is significantly up-regulated in the cervical cancer samples in comparison with that in normal samples. Moreover, the ROC data showed the potential ability of p16INK4a under determined conditions as a diagnostic marker for CIN 2-3 staging and invasive cervical cancer. The molecular typing disclosed the attendance of HPV DNA in 44.4% of cases (32/72) with a predominance of HPV type 16., Conclusion: The molecular biomarker p16INK4a can be a good candidate for the early diagnosis and prognosis of cervical cancer in HPV-infected patients. Considering the increase in the expression level of p16INK4a in cancer and precancer tissues, p16INK4a may be used for early detection of cervical cancer., Competing Interests: Conflict of interests The authors declare that there is no conflict of interest., (Copyright © Iranian Public Health Association & Tehran University of Medical Sciences.)

Given the global outbreak of breast cancer and its debilitating effect on women's health, it is not surprising that tremendous efforts have been made with an aim of shedding more light on the mechanisms involved in the pathogenesis of this type of cancer. Among the long list of risk factors associated with this malignancy, recently, the role of microRNAs (miRNAs or miRs) has turned into a hotspot for breast cancer investigations. miRNAs approximately 20 nucleotides in length and are located in either an exon or an intron, playing a role in the regulation of gene expression. In the present study, we extracted RNA from both the serum and cancerous tissue of breast cancer patients and after synthesizing the cDNA, we performed quantitative PCR to determine the expression levels of miR-9 and miR-192. The resulting data revealed that while the mRNA expression level of miR-9 was significantly decreased in the breast cancer tissues, there was no noticeable change in the expression level of this miRNA in the serum samples. Likewise, we found that the marked downregulation of miR-192 was only restricted to the cancerous tissues, but was not found in the serum of patients. Based on the meaningful downregulation of the expression of miR-9 and miR-192, this study provides a plausible framework for these miRNAs as effective biomarkers for breast cancer patients., (Copyright © 2019, Spandidos Publications.)

Introduction: Breast cancer (BC) is the most common malignancy affecting females worldwide. Various risk factors play a role in the developing of BC. Infectious agents like viruses have been proposed for this cancer and Epstein-Barr virus (EBV) is a widely researched candidate virus. This study detects the presence of EBV-DNA in breast cancer patients., Methods: The study was conducted on 59 formalin-fixed paraffin-embedded (FFPE) tissue blocks samples of women with breast carcinoma and 11 non-neoplastic breast controls. The DNA was extracted for all the samples. Then detection of EBNA1 EBV was done by polymerase chain reaction (PCR)., Results: EBV was detected in 6.7% (4/59) of patients while all breast control samples were negative. All patients with positive EBV-DNA were high tumor grades (II, and III). Also, they had a low level of educations., Conclusions: According to our findings, it can be suggested that EBV may have a potential role in breast cancer development. However, this study provides substantial but not conclusive evidence for the involvement of viruses in BC disease development. Therefore, future investigations are needed to elucidate the exact role of EBV in breast cancer., .

Oncogenic viruses are one of the most important causes of cancer worldwide. The pathogens contribute to the establishment of human malignancies by affecting various cellular events. Epigenetic mechanisms, such as histone modification methylation/demethylation, are one of the most critical events manipulated by oncogenic viruses to drive tumorigenesis. Histone modifications are mediated by histone acetylation and deacetylation, regulated by histone acetyltransferases (HATs) and histone deacetylases (HDACs), respectively. Dysregulation of HDACs activity affects viral tumorigenesis in several ways, such as manipulating tumor suppressor and viral gene expression. The present review aims to describe the vital interactions between both cancer-caused/associated viruses and the HDAC machinery, particularly by focusing on those viruses involved in gastrointestinal tumors, as some of the most common viral-mediated cancers., (© 2019 John Wiley & Sons, Ltd.)

In silico analysis is the most important approach to understand protein structure and functions, and the most important problem for designing and producing a fusion construct is producing large amounts of functional protein. Clostridium perfringens type A and Clostridium septicum produce alpha ( plc ) and alpha toxins respectively. C. perfringens can cause gas gangrene and gastrointestinal diseases. C. septicum can cause traumatic and non-traumatic gas gangrene. The aim of current research was in silico analysis of a chimeric fusion protein against C. perfringens type A and C. septicum alpha toxins. Firstly, the chimeric fusion gene was designed according to nucleotide sequences of C. perfringens type A alpha (KY584046.1) and C. septicum alpha (JN793989.2) toxin genes and then its fusion protein is constructed by amino acid sequences of C. perfringens type A and C. septicum alpha toxins. Secondly, online software was used to determine prediction of secondary and tertiary structures and physicochemical characteristics of the fusion protein. Finally, the validation of the fusion protein was confirmed by Rampage and proSA program. The designed fusion protein has 777 amino acids in length. TASSER server and physicochemical parameters are showed: C-score = - 2.68 and molecular weight = 87.9 KD respectively. Rampage and proSA software revealed the fusion protein is valid. Deposited accession number for the sequence of the fusion gene in the GenBank is MK908396. The designed fusion protein is valid and functional. Thus, the fusion gene could be used for clone and expression in a proper prokaryotic cell and also as a recombinant vaccine candidate., Competing Interests: Conflict of interestThe authors declare that there is no conflict of interest., (© The Author(s) 2020.)

Objective: Breast cancer is known as one of very important cancers among females, given that a variety of external (i.e., environmental risk factors) and internal factors (i.e., genetics, and epigenetics) are related to the emergence and progression of breast cancer. Among genetic and epigenetic factors, DNA methyltransferase and EMT related genes have critical roles in breast cancer pathogenesis. In the study presented here, we investigated expression of DNA methyltransferases (e.g., DNMT1, DNMT3A and DNMT3B) and EMT related genes (e.g., E-cadherin, Snail, ZEB-1)., Methods and Materials: Tissue samples were collected from 18 cancer and 24 normal breast tissues. We evaluated the expression levels of DNA methyltransferases and EMT related genes using Quantitative real-time PCR (qRT-PCR)., Results: Our results indicated that the expression levels of ZEB-1, Snail, and DNMT3B were increased in breast cancer subjects in comparison to the control group. On the other hand, there was a significant decrease in E-cadherin expression in breast cancer tissues in comparison to the normal tissues. Moreover, there were no significant changes for DNMT1 and DNMT3A expression in breast cancer tissues when compared to the normal tissues., Conclusion: Taken together, our finding show that up regulation of ZEB-1 and Snail could be associated with down regulation of E-cadherin and results in promotion of cancer cell invasion. Moreover, down regulation of E-cadherin may be related to deterioration of DNMT3B inpatients with breast cancer.

Objective: Breast cancer is one of the most common health problems. It has been suggested that several risk factors, either considered as external or internal, play a critical role in the pathogenesis of breast cancer, which among them, HERV-k, has the most fundamental role. In the present study, we aimed to evaluate the role of HERV-k env, gag, rec, np9 expressions in breast cancer progression., Materials and Methods: We collected 40 breast cancer tissues and their normal adjacent ones. After extracting the RNA of breast samples, we evaluated the expression of HERV-k env, gag, rec, np9 by using Quantitative real-time PCR (qRT-PCR)., Results: The resulting data revealed that while there was a meaningful increase in the expression level of HERV-k env, gag and np9 in breast cancer tissues ( P  ≤ 0.01, 0.05, 0.05, respectively), we failed to find any significant elevation in the expression level of rec mRNA level., Conclusion: The results of our study suggested that there is a plausible correlation between the mRNA expression level of HERV-K env, gag and np9 and the progression of breast cancer, proposing these markers as promising biomarkers to diagnose breast cancer., Competing Interests: Competing interestsThe authors declare no conflicts of interests., (© The Author(s). 2019.)

Seven oncogenic viruses are known for tumorigenesis and contribute to 12% of all human cancers. The oncogenic factors, the target tissue, and pathology of cancer vary among these viruses with several mechanisms proposed for the initiation and development of cancer. Aneuploidy in cells is associated with anomalies in chromosome number that can be a hallmark of cancer, a disease defined by expanded proliferative potential. In this review, we summarize the different mechanisms of aneuploidy and furthermore discuss recent findings of the role of viral oncoproteins in inducing cellular aneuploidy that might facilitate tumorigenesis. Improved understanding of viral oncogenesis may help to find new strategies for controlling virus-associated cancers., (© 2019 John Wiley & Sons, Ltd.)

Background: Finding new biomarkers for the early detection of cervical cancer is an essential requirement in this field. In this study, we aimed to evaluate the expression level of potential biomarkers in progression of cervical cancer in patients with cervical cancer compared to normal subjects., Methods: The expression levels of tissue and serum miRNAs, including miR-9, miR-192 and miR-205, were investigated in 36 normal, 18 precancer, and 18 cervical cancer samples using real-time polymerase chain reaction., Results: The results showed the higher significant expressions of miR-9, miR-192 and miR-205 in the tissue of cancer samples than those in the normal samples. Moreover, the miR-192 and miR-205 expression were significantly increased in the cancer group in comparison with the precancer group. Examination of serum samples revealed the increase in the expression level in the cancer groups than in the normal samples, for miR-9, miR-192 and miR-205 and the expressions of miR-9, miR-192 and miR-205 were significantly up-regulated in the precancer group in comparison with the normal group. Also the expression of miR-205 was remarkably increased in the cancer group in comparison with the precancer group. The receiver operating characteristic (ROC) analyses showed the highest area under the curve value for miR-192., Conclusions: Given the increased expression level of miR-192 in cancer and in precancerous tissue and serum compared with the normal tissue and serum validated by analysing the ROC curve, miR-192 can be used as potential biomarker for the early detection of cervical cancer.

Objective: Cancer is one of the common diseases in the world, and cervical cancer is the fourth one. In this type of cancer, many risk factors, especially infectious diseases, such as human papilloma virus (HPV) and gram-negative bacteria can have important effects on the expression of epithelial to mesenchymal transition related genes like Snail, E-cadherin, and ZEB-1, responsible for connecting cell tissues. In this study, we have investigated the effect of Escherichia coli O111:B4 Lipopolysaccharide (LPS) on HPV positive cell line (HeLa), the expression level of the (Snail, E-cadherin, and ZEB-1), HPV oncogenes (E6, E7) and also microRNA-9, 192. Materials and Methods: HeLa cell line was treated with LPS to analyze Snail, E-cadherin, ZEB-1, E6, E7 and also microRNA-9, 192 expression by quantitative real-time PCR in 24, 48 and 72 hours. Results: Quantitative real-time PCR revealed a significant reduction in E-cadherin mRNA level at 10ug/L of LPS in three time-points and after 24 hours at 5ug/L of LPS; however, ZEB-1 at 10ug/L of LPS and Snail at 5, 10ug/L of LPS are up-regulated. E7 also illustrated a slight increase, but we did not find any relationship between E7 and LPS treatment. Additionally, there are upward trends in microRNA-9, 192 levels. Conclusion: The result of this study, LPS is able to reduce E-cadherin expression, caused by increase in repressor E-cadherin protein expression and some microRNAs, probably. Since bacterial infection can be in cervical site, it is likely to be effective in reducing the E-cadherin expression in the EMT and enhance cancer process, therefore; removing these infections by using the appropriate antibiotics may result in slowing down this process, which requires more research.

HRSV is a principle cause of infant hospitalization, childhood wheezing and a common pathogen in the elderly. Limited information exists regarding HRSV genotypes in Iran. In order to better understand HRSV strain diversity, we performed an in-depth evaluation of the genetic variability of the HRSV F protein detected in children under two years of age that, presented with acute respiratory symptoms during 2015-2016 in Tehran. A total of 180 nasopharyngeal swabs were evaluated. The HRSV positive samples were genotyped for G and F gene sequences using RT-PCR and sequencing methods. Phylogenetic analysis was performed using the neighbor-joining and maximum likelihood methods. Genetic and antigenic characteristics of the F gene, nucleotide and amino acids in significant positions and immune system binding regions, as well as the p-distance, positive/negative selection site, linear epitopes and glycosylation sites were investigated in all selected sequences. Among the 83 HRSV positive samples, the Fifty-five cases were successfully sequenced. All of them were classified as subgroup A and belonged to the ON-1 genotype, which possessed 72-nt duplication in the G gene. This study is the first report on the emergence of ON-1 in Iran. ON-1 Iranian sequences clustered in three lineages according to virus fusion (F) gene variations. F gene sequence analysis showed that all genetic changes in the isolates from Iran were base substitutions and no deletion/insertions were identified. The low dN/dS ratio and lack of positively selected sites showed that the fusion genes found in the strains from Iran are not under host selective pressure. Continuing and long-term molecular epidemiological surveys for early detection of circulating and newly emerging genotypes are necessary to gain a better understanding of their epidemic potential., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Forkhead box (FOX) proteins play a crucial role in regulating the expression of genes involved in multiple biological processes, such as metabolism, development, differentiation, proliferation, apoptosis, migration, invasion, and longevity. Deregulation of FOX proteins is commonly associated with cancer initiation, progression, and chemotherapeutic drug resistance in many human tumors. FOX proteins deregulate through genetic events and the perturbation of posttranslational modification. The purpose of the present review is to describe the deregulation of FOX proteins by oncoviruses. Oncoviruses utilize various mechanisms to deregulate FOX proteins, including alterations in posttranslational modifications, cellular localization independently of posttranslational modifications, virus-encoded miRNAs, activation or suppression of a series of cell signaling pathways. This deregulation can affect proliferation, metastasis, chemotherapy resistance, and immunosuppression in virus-induced cancers and help to chronic viral infection, development of gluconeogenic responses, and inflammation. Since the PI3K/Akt/mTOR signaling pathway is the upstream FOXO, suppressing it can cause FOXO function to return, and this can be one of the reasons for patients to recover from the infection of the viruses used to treat these inhibitors. Hence, FOX proteins could serve as prognosis markers and target therapy specifically in cancers caused by oncoviruses., (© 2018 Wiley Periodicals, Inc.)

Human tumor viruses are either casually linked or contribute in the development of human cancers. Viruses can stimulate oncogenesis through affecting diverse biological pathways in human cells. Growing data have demonstrated frequent involvement of one of the most characteristic parts of cellular epigenetic machinery, DNA methylation, in the oncogenesis. DNA methylation of cellular genes is catalyzed by DNA methyltransferases (DNMTs) as a key effector enzyme in this process. Dysregulation of DNMTs can cause aberrant gene methylation in promoter of cancer-related genes including tumor suppressor genes, resulting in gene silencing. In this regard, the role of tumor viruses is remarkable. Here, in this review, we used published information to elucidate whether tumor viruses are able to manipulate DNMT regulation, and if so, what are its consequences in the process of oncogenesis. This essay also aims to shed light on which cellular pathways have been engaged by viruses to induce DNMTs., (© 2018 John Wiley & Sons, Ltd.)

The nuclear factor erythroid 2 related factor 2 (Nrf2) is a major regulator of intracellular inducible defense systems against harmful endogenous and exogenous substances in the body. Under normal conditions Nrf2 is mainly binds to keap1 and located in the cytoplasm. However, in response to oxidative and electrophile stress, Nrf2 translocated to the nucleus and link to anti-oxidant response elements to induce the transcription of cytoprotective genes. Most viruses cause oxidative stress and increase the activity of radicals and reactive oxygen species (ROS), subsequently, the cellular protection system activates the Nrf2 and increases the expression of cytoprotective genes. However, in some cases, the activation of Nrf2 is not ROS-dependent, and is carried out directly via the ROS-independent pathway. Many viruses cause the activation of Nrf2, which is involved in the pathogenesis and the progression of the virus infection and even in its chronic form. However, some viruses inhibit the activation of Nrf2, in which case the virus also benefits of this mechanism to maintain the homeostasis of the cell. However, the challenge between the Nrf2/ARE signaling pathway of and viral infections is unknown in some cases, and in order to know more details in this regard, a more detailed seems necessary., (© 2018 Wiley Periodicals, Inc.)

Objectives: Colorectal cancer (CRC) is one of the most common cancers and a major cause of cancer-related death worldwide. The early diagnosis of colorectal tumors is one of the most important challenges in cancer management. MicroRNAs (miRNAs) have provided new insight into CRC development and have been suggested as reliable and stable biomarkers for diagnosis and prognosis. This study's objective was to analyze the differential expression of miRNAs at differentstages of CRC searching for possible correlation with clinicopathological features to examine their potential value as diagnostic biomarkers., Materials and Methods: In this case-control study, plasma and matched tissue samples were collected from 74 CRC patients at stage II-IV as well as blood samples from 32 healthy controls. After exhaustive study of the current literature, eight miRNAs including miR-200c, 20a, 21, 31,135b, 133b,145 and let-7g were selected. The expression level of the miRNAs was assayed by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Statistical analysis, including t test , Mann-Whitney U, Kruskall-Wallis tests and receiver operating characteristic (ROC) curve was applied, where needed., Results: Significantly elevated levels of miR-21, miR-31, miR-20a, miR-135b, and decreased levels of miR- 200c, miR-145 and let-7 g were detected in both plasma and matched tissue samples compared to the healthy group (P<0.05). However, no significant differences were observed in the expression level of plasma and tissue miR-133b (P>0.05). ROC for tissue miRNAs showed an area under the ROC curve (AUC) of 0.98 and P<0.001 for miR-21, 0.91 and P<0.001 for miR-135b, 0.91 and P<0.001 for miR-31, and 0.92 and P<0.001 for miR-20a., Conclusions: Our results indicate that the expression levels of microRNAs are systematically altered in CRC tissue and plasma. In conclusion, detection of miR-21, miR-135b, miR-31 and miR-20a levels in the tissue might be helpful to illuminate the molecular mechanisms underlying CRC carcinogenesis and serve as tumor-associated biomarkers for diagnosis., Competing Interests: There is no conflict of interest in this study., (Copyright© by Royan Institute. All rights reserved.)

Gastrointestinal cancers are a global public health problem, which represent a vast majority of all cancer-caused deaths in both men and women. On the other hand, viral pathogens have been long implicated as etiological factors in the onset of certain human cancers, including gastrointestinal tumors. In this regard, Human Papilloma Virus (HPV), Epstein-Barr Virus (EBV), and John Cunningham Virus (JCV) have been more strongly suggested to be involved in gastrointestinal carcinogenesis; so that, the association of HPV with oropharyngeal and anal cancers and also the association of EBV with gastric cancer have been etiologically confirmed by epidemiological and experimental investigations. Although, the association of other viruses is less evident, but may rely on co-factors for their oncogenic roles. Therefore, to improve the prevention and treatment of these classes of cancer, their association with viral agents as potential risk factors should be investigated with care. In this respect, the present review has focused on the existing literature on the subject of viral involvement in gastrointestinal tumorgenesis, by covering and discussing various gastrointestinal cancers, corresponding viral agents and their oncogenic aspects and then summarizing evidences either supporting or rejecting a causal role of these pathogens in gastrointestinal malignancies., (© 2017 Wiley Periodicals, Inc.)