Cell Death Mechanisms in Esophageal Squamous Cell Carcinoma Induced by Vesicular Stomatitis Virus Matrix Protein

OBJECTIVES: Vesicular stomatitis virus (VSV) is under development as an oncolytic virus due to its preferential replication in cancer cells and oncolytic activity, however the viral components responsible have not yet been determined. In this study the effects of VSV wild-type (wt) and M51R-mutant matrix proteins (M51R-mMP) on apoptosis, pyroptosis, necroptosis, and autophagy pathways, in an esophagus cancer cell line (KYSE-30) were investigated. METHODS: The KYSE-30 cells were transfected with pcDNA3.1 plasmids encoding wt or M51R-mMP, and apoptosis, pyroptosis, necroptosis, and autophagy were evaluated 48 and 72 hours after transfection. RESULTS: KYSE-30 cells transfected with VSV wt and M51R-mMPs significantly reduced cell viability to < 50% at 72 hours post-transfection. M51R-MP significantly increased the concentration of caspase-8 and caspase-9 at 48 and 72 hours post-transfection, respectively ( p < 0.05). In contrast, no significant changes were detected following transfection with the VSV wt plasmid. Moreover, VSV wt and M51R-mMP transfected cells did not change the expression of caspase-3. VSV wt and M51R-mMPs did not mMP change caspase-1 expression (a marker of pyroptosis) at 48 and 72 hours post-transfection. However, M51R-mMP and VSV wt transfected cells significantly increased RIP-1 (a marker of necroptosis) expression at 72 hours post-infection ( p < 0.05). Beclin-1, a biomarker of autophagy, was also induced by transfection with VSV wt or M51R-mMPs at 48 hours post-transfection. CONCLUSION: The results in this study indicated that VSV exerts oncolytic activity in KYSE-30 tumor cells through different cell death pathways, suggesting that M51R-mMP may potentially be used to enhance oncolysis.

Prevalence and genotyping of torque teno virus in HBV/HIV and chronic HBV patients in Iran

Background: Torque teno virus [TTV] was the first human Anelloviridae detected in a Japanese patient with an unknown type of hepatitis in 1997. TTV is by far the first known single-stranded circular DNA virus infecting human. In spite of its widespread nature in human population, its pathogenesis is still unclear. In addition, information regarding TTV infection in Iranian population is limited. Therefore, we attempted to determine the prevalence and genotype of TTV in three groups: HIV/HBV patients, chronic hepatitis B patients, and healthy individuals

Methods: The presence of TTV DNA in sera was investigated using PCR. The primer sets encompassing two 5'-UTR and N22 regions were used, and the positive products were collected for sequencing. Phylogenetic tree was generated based on N22 region and using the MEGA 7 software

Results: TTV DNA was detected in 452 patients with HIV/HBV and chronic hepatitis B, as well as in healthy control groups. The results from PCR indicated positive rates for these three groups, 48%, 54%, and 49.3% using 5'-UTR primer and 15.1%, 12%, and 8% using N22 primer, respectively

Conclusion: Five genogroups were observed, which the second group was found to be the most frequent. The results of 5'-UTR primer showed more prevalence of TTV DNA comparing to N22 primer in patients and healthy control

Is there any evidence for a viral cause in achalasia?

Background:Achalasia, as an incurable disease is defined by the lack of normal esophageal peristalsis and loss of lower esophageal sphincter relaxation due to impaired myenteric neural plexus. The exact cause of myenteric neural cells degeneration in achalasia is still unknown. One hypothesis is that certain neurotropic viruses and autoimmune factors cause the inflammatory response in myenteric network, which consequently destroy neural cells. This study was designed to find the evidence of viral causes of achalasia

Methods: In this case-control study, 52 patients with achalasia and 50 controls referred to Shariati Hospital, were evaluated for the genome of neurotropic viruses, HPV, and adenovirus by polymerase chain reaction [PCR] and reverse transcription [RT] PCR techniques

Results:Genome assessment of neurotropic DNA viruses turned out negative in the patients, however, the genome of HSV-1 [Herpes simplex virus] was found in tissues of six controls. No neurotropic RNA viruses were observed in the tissue samples and whole blood of both the patients and controls.Among non-neurotropic viruses, adenovirus genome was positive in tissues of two out of 52 patients and three out of 50 controls. In addition, one out of 52 patients and two out of 50 controls were positive for HPV infection in tissues

Conclusion: We could not detect any significant relationship between achalasia and HPV, adenovirus, and neurotropic viruses in the cases. Nevertheless, it does not exclude the hypothesis of either an alternate viral species or resolved viral infection as the etiology of achalasia

Esophageal cancer in golestan province, Iran: a review of genetic susceptibility and environmental risk factors

Esophageal squamousi cell carcinoma [ESCC] is an aggressive tumor that is typically diagnosed only when the tumor has gained remarkable size, extended to peripheral tissues, and led to dysphagia. Five-year survival of advanced cancer is still very poor [19%], even with improved surgical techniques and adjuvant chemoradiation therapy

Therefore, early detection and prevention are the most important strategies to reduce the burden of ESCC

Our review will focus on the studies conducted in Golestan province, an area with a high prevalence of ESCC in northern Iran. We review three aspects of the research literature on ESCC: epidemiological features, environmental factors [including substance abuse, environmental contaminants, dietary factors, and human papilloma virus [HPV], and molecular factors [including oncogenes, tumor suppressor genes, cell cycle regulatory proteins, and other relevant biomarkers]

Epidemiological and experimental data suggest that some chemicals and lifestyle factors, including polycyclic aromatic hydrocarbons [PAHs], cigarette smoking, opium use, and hot tea drinking are associated with the development of ESCC in Golestan

HPV infects the esophageal epithelium, but so far, no firm evidence of its involvement in esophageal carcinogenesis has been provided. Some of these factors, notably hot tea drinking, may render the esophageal mucosa more susceptible to injury by other carcinogens

There are few studies at molecular level on ESCC in Golestan

Increasing awareness about the known risk factors of ESCC could potentially reduce the burden of ESCC in the region. Further studies on risk factors, identifying high risk populations, and early detection are needed

Genistein induces a protective immunomodulatory effect in a mouse model of cervical cancer

Genistein [GEN], a naturally occurring flavonoid present in soy bean, has attracted scientific interest for its possible benefits in cancer. The potential immunomodulatory effects of genistein on the immune system and against TC-1 tumor cell line were evaluated in adult female C57BL/6 mice. Mice were treated with GEN 10 days before to 10 days after the tumor induction. Thirty days after the last GEN treatment, lymphocyte proliferation, Lactase Dehydrogenase [LDH] cytolytic activity and cytokine secretion were analyzed in GEN and control groups. The results showed that ingestion of genistein significantly increased lymphocyte proliferation and LDH release. Furthermore, the treatment with genistein also caused a significant increment in interferon gamma [IFN-alpha]. In addition, the treatment achieved significant therapeutic effect in tumor models compared to the control group. These results indicated that the effect of GEN on tumor growth may be attributed to its effect on lymphocyte proliferation, cytolytic activity and IFN-alpha production. These results demonstrate that GEN exerts an immunomodulatory effect in a mouse model of Human Papillomavirus [HPV] associated-cervical cancer

Incidence of childhood cancers in Golestan province of Iran

This paper presents the incidence rates of childhood cancers using the data obtained from Golestan population based cancer registry [GPCR] between 2004 and 2006. GPCR registers only primary cancers based on standard protocols of the international association of cancer registries [IACR]. We collect data on newly diagnosed [incident] cancer cases from all public and private diagnostic and therapeutic centers of the whole province. CanReg-4 software was used for data entry and analysis. Totally 5076 cancer cases [all ages] were diagnosed in GPCR between 2004 and 2006. Of these, 139 [2.74%] were children [aged 0-14 years] with mean [ +/- SD] age of 8.06 [ +/- 4.48] years. The age standardized incidence rates for childhood cancer were 119.8 and 78.3 per 1000000 person-years in male and female children, respectively. Leukemia was the most common childhood cancer in Golestan province of Iran. Lymphomas and central nervous system tumors were the second and third ones, respectively. The incidence rates of childhood cancers were relatively high in Golestan province of Iran. So, controlling of childhood cancers should be mentioned as an important issue in health policy making in this area

[Nutritional characteristics in patients with colorectal cancer in Golestan Province of Iran, a case-control study]

Colorectal cancer is the third common malignancy in the world. Personal habits including life style and nutrition have been proposed as risk factors of colorectal cancer. We conducted this study to assess the nutritional characteristics in colorectal cancer patients in Golestan province of Iran. This case-control study was done on 47 colorectal cancer cases, diagnosed during 2004-05 and 47 healthy controls. A questionnaire containing socio-demographic and nutritional characteristics [FFQ] was filled for each of the participants. Chi square test was used to assess the relationship between variables. In each of the two groups, 40.4% were females and 59.6% were males. The mean +/- SD age of age in cases and controls were 52.4 +/- 13.4 and 52.1 +/- 13.1 years, respectively. Total energy expenditure of higher than 1837.5 Kcal/day was significantly related to colorectal cancer [OR= 3.8; 95% CI: 1.2-11.3]. Colorectal cancer risk was higher in individual with frying cooking method [OR=3; 95% CI: 0.8-11.1]. The risk of colorectal cancer was 6.5 times higher in individuals with fat consumption of higher than 118.5 grams/day [95% CI: 1.5-28.8].No significant relationship was seen between vegetables consumption and the risk of colorectal cancer. This study showed that high total energy expenditure, high fat consumption and using frying method for cooking are risk factors of colorectal cancer in Golestan province in Northern of Iran

Seroprevalence of hepatitis B virus and its co-infection with hepatitis D virus and hepatitis C virus in Iranian adult population.

CONTEXT: Hepatitis B virus (HBV) infection is one of the most prevalent public health problems worldwide (especially in developing countries). AIMS: This study was carried out to determine the seroprevalence of HBV and its co-infection with hepatitis D (HDV) and C (HCV) viruses in the northeastern part of Iran. SETTING AND DESIGN: A population-based cross-sectional study in Iran. MATERIALS AND METHODS: As many as 1,850 subjects were explored for HBsAg. Anti-HDV and anti-HCV antibodies were assessed in HBsAg-positive cases. STATISTICAL ANALYSIS USED: Proportions were compared by Chi-square and Fisher's exact tests. RESULTS: The mean age of subjects was 43.86 +/- 11.2 years. The age- and sex-standardized prevalence for HBsAg positivity was 9.7%. It was higher in males than in females (OR: 1.28; 95% CI: 0.9-1.7). The risk of infection in singles was significantly higher than in married cases (OR: 2.13). Eight (5.8%) of HBsAg-positive cases were infected with HDV and 17 (12.3%) were positive for anti-HCV antibody. CONCLUSION: This study demonstrates that the prevalence of HBsAg seropositivity in Golestan province of Iran is higher than the levels reported by WHO and previous studies from Iran. It is very important, especially for health providers and policy makers, to recognize the risk factors of HBV infection and its co-infection with HDV and HCV in this area and design effective preventive programs.