Browsing by Author "J. Schneider, Robert"

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Abstract 3302: High incidence of MAC387 positive cells in the carcinoma tissues of inflammatory breast cancer patients correlate with the detection of multiple human Cytomegalovirus genotypes and invasive properties of the disease
(American Association for Cancer Research, 2016) Taha Mohamed, Hossam; Gadalla, Ramy; Abdel Aziz Ibrahim, Sherif; Akram Nouh, M.; El-Shinawi, Mohamed; J. Schneider, Robert; Mostafa Mohamed, Mona
Introduction: Previously we showed that the incidence of multiple human cytomegalovirus (HCMV) genotypes in the carcinoma tissues of inflammatory breast cancer (IBC) patients plays essential role in the disease progression. Primary HCMV infection to monocytes induces differentiation and biological turnover of monocytes to macrophages. In addition infected macrophages serves as “mobile vectors” for virus spreading and dissemination to different organs mainly by transendothelial migration. In addition we screened for the infiltration of CD14+ and CD68+ monocytes/macrophages markers in the carcinoma tissues of IBC versus non-IBC patients we showed that of CD14+ cells highly infiltrate tumor microenvironment (TME) of IBC patients compared to non-IBC. Aims: In the present study we aim to 1) Assess the level of expression of MAC387 protein by monocytes/macrophages infiltrating TME of IBC versus non-IBC patients; 2) Test the correlation between the density of infiltrated MAC387+ cells and the incidence of different HCMV genotypes in carcinoma tissues of IBC versus non-IBC tissues. Since MAC387 found to be more common in cancers characterized by high metastatic properties we will also 3) determine whether the expression of MCA387 correlate with lymph-node metastasis and lymphovascular invasion in IBC versus non-IBC breast cancer patients. Materials and Methods: A total of 135 breast cancer patients (91 non-IBC and 44 IBC) were enrolled to the present study during the period of January 2012 to September 2015 from Ain Shams university Hospitals. Detection of MAC387 marker was assessed by immunohistochemistry and HCMV genotypes were detected using multiplex PCR methodology. Results: MAC387+ positive cells were more prevalent in IBC tissues than non-IBC tissues (p = 0.4). Incidence of higher number of MAC387+ cells were positively correlate with higher number of metastatic lymph nodes in both IBC and non-IBC patients r = 0.807 and 0.779 respectively. Moreover, Incidence of higher number of MAC387+ cells found to be positively correlate with lymphovascular invasion in IBC patients r = 0622. Detection of multiple HCMV genotypes was statistically higher (p = 0.04) in IBC tissues in comparison with non-IBC tissues. Moreover, triple negative non-IBC and IBC tissues showed higher incidence of multiple HCMV genotypes in comparison with hormonal positive non-IBC and IBC tissues. of the monocytes/macrophages MAC387+ positive cells were more prevalent in IBC tissues showed multiple HCMV genotypes in comparison with IBC tissues showed single HCMV genotype (p = 0.46). Conclusion: MAC387+ positive cells were more prevalent in IBC tissues and correlate with presence of multiple HCMV genotypes and high invasive properties of the disease.
Abstract 4788: Detection of different genotypes of Human Cytomegalovirus in breast cancer patients.
(American Association for Cancer Research, 2013) Taha Mohamed, Hossam; El-Shinawi, Mohamed; Bashtar, Abdel-Rahman; Tarek abdel Salam, El-Said; J. Schneider, Robert; Mostafa Mohamed, Mona
Background: Human Cytomegalovirus (HCMV) is an endemic herpes virus that re-emerges in cancer patients enhancing oncogenic potential. Recent studies have shown that HCMV infection is associated with certain types of cancer morbidity such as glioblastoma; Although HCMV has been detected in breast cancer tissues. The ability of HCMV to infect diverse organs and cell types in vivo has been attributed to strain variations in certain genes of the virus. The relationship between genetic variants of the envelope glycoprotein genes of HCMV and disease outcome has been studied recently, among these variable genes HCMV ORF UL73 (envelope glycoprotein N). Aims: The aims of the present study were to 1) Screen for the infection of Human cytomegalovirus infection in inflammatory versus non-inflammatory breast cancer patients and 2) test the frequency of occurrence of multiple genotypes of HCMV glycoprotein N in IBC versus Non-IBC patients, to determine if there is any mixed infections by multiple genotypes in paired clinical specimens obtained from patients. Material and Methods: A total 93 (62 Non-IBC and 31 IBC) women diagnosed with breast cancer by clinical examination, ultrasound, mammography, and confirmed by biopsy (tru-cut) were enrolled into this study from Ain Shams university Hospitals. During modified radical mastectomy or conservative breast surgery carcinoma and non carcinoma tissues with peripheral blood were collected to detect the presence of Human cytomegalovirus DNA using nested PCR. HCMV glycoprotein N polymorphism (gN) was detected using multiplex PCR by using specific primers to each gN genotype which enable us to detect any mixed genotypes infection. Results: Analysis of the HCMV nested PCR to the carcinoma tissues showed that 63% of non-IBC carcinoma tissues were HCMV-DNA positive and 37% were HCMV-DNA negative. In IBC 80% of carcinoma tissues were HCMV-DNA positive and 20% were HCMV-DNA negative. Application of multiplex PCR for gN gene on HCMV positive carcinoma tissues (25 IBC and 32 Non-IBC) revealed that gN-1 genotype was detected in 25% of the non-IBC patients and 32% of the IBC patients, While gN-3b was detected in 6.25% of non-IBC patients and 4% of the IBC patients. Genotype gN-4a was detected in 9.38% of Non-IBC patients and in 4% of the IBC patients, while gN-4b\c was detected in 59.37% of Non-IBC patients and in 60% of the IBC patients. Also revealed mixed infection of gN-1+ gN-4b\c, gN-3b + gN-4b\c and gN-4a + gN-4b\c in Non-IBC patients and gN-1+ gN-4b\c, gN-3b + gN-4b\c in IBC patients. Conclusion: The frequency of HCMV infection in IBC was higher than Non-IBC patients; however the most dominant HCMV gN genotypes in IBC and Non-IBC are similar.
Human cytomegalovirus infection enhances NF-κB/p65 signaling in inflammatory breast cancer patients
(Public Library of Science, 2013) El-Shinawi, Mohamed; Taha Mohamed, Hossam; A. El-Ghonaimy, Eslam; Tantawy, Marwa; Younis, Amal; J. Schneider, Robert; Mostafa Mohamed, Mona
Human Cytomegalovirus (HCMV) is an endemic herpes virus that re-emerges in cancer patients enhancing oncogenic potential. Recent studies have shown that HCMV infection is associated with certain types of cancer morbidity such as glioblastoma. Although HCMV has been detected in breast cancer tissues, its role, if any, in the etiology of specific forms of breast cancer has not been investigated. In the present study we investigated the presence of HCMV infection in inflammatory breast cancer (IBC), a rapidly progressing form of breast cancer characterized by specific molecular signature. We screened for anti-CMV IgG antibodies in peripheral blood of 49 non-IBC invasive ductal carcinoma (IDC) and 28 IBC patients. In addition, we screened for HCMV-DNA in postsurgical cancer and non-cancer breast tissues of non-IBC and IBC patients. We also tested whether HCMV infection can modulate the expression and activation of transcriptional factor NF-κB/p65, a hallmark of IBC. Our results reveal that IBC patients are characterized by a statistically significant increase in HCMV IgG antibody titers compared to non-IBC patients. HCMV-DNA was significantly detected in cancer tissues than in the adjacent non-carcinoma tissues of IBC and IDC, and IBC cancer tissues were significantly more infected with HCMV-DNA compared to IDC. Further, HCMV sequence analysis detected different HCMV strains in IBC patients tissues, but not in the IDC specimens. Moreover, HCMV-infected IBC cancer tissues were found to be enhanced in NF-κB/p65 signaling compared to non-IBC patients. The present results demonstrated a correlation between HCMV infection and IBC. Etiology and causality of HCMV infection with IBC now needs to be rigorously examined.
Inflammatory and Non-inflammatory Breast Cancer: A Potential Role for Detection of Multiple Viral DNAs in Disease Progression
(Springer US, 2016) El-Shinawi, Mohamed; Taha Mohamed, Hossam; Hesham Abdel-Fattah, Hadeer; Abdel Aziz Ibrahim, Sherif; S. El-Halawany, Medhat; Akram Nouh, M.; J. Schneider, Robert; Mostafa Mohamed, Mona
Background Inflammatory breast cancer (IBC) is the most lethal form of breast cancer. Multiple viral infections in IBC tissues were found to be associated with disease pathogenesis. Objective The aim of the present study was to correlate the incidence of viral DNA with breast cancer progression. Materials and Methods Overall, 135 women diagnosed with breast cancer were enrolled in this study. Using polymerase chain reaction and sequencing assays, we determined the incidence of human papillomavirus types 16 and 18 (HPV-16 and -18), human cytomegalovirus (HCMV), Epstein–Barr virus, human herpes simplex virus type 1 and 2, and human herpes virus type 8 (HHV-8) in breast carcinoma tissue biopsies. We also assessed the expression of the cell proliferation marker Ki-67 by immunohistochemistry in association with the incidence of viral DNA. Results HCMV and HPV-16 were the most detected viral DNAs in breast carcinoma tissues; however, the frequency of HCMV and HHV-8 DNA were significantly higher in IBC than non-IBC tissues. Moreover, the prevalence of multiple viral DNAs was higher in IBC than non-IBC tissues. The incidence of multiple viral DNAs positively correlates with tumor size and number of metastatic lymph nodes in both non-IBC and IBC patients. The expression of Ki-67 was found to be significantly higher in both non-IBC and IBC tissues in which multiple viral DNAs were detected. Conclusions The incidence of multiple viral DNAs in IBC tissues was higher compared with non-IBC tissues. The present results suggest the possibility of a functional relationship between the presence of multiple viral DNAs and disease pathogenesis.
Inflammatory breast cancer: high incidence of detection of mixed human cytomegalovirus genotypes associated with disease pathogenesis
(Frontiers, 2014) Taha Mohamed, Hossam; El-Shinawi, Mohamed; Akram Nouh, M.; Bashtar, Abdel-Rahman; Tarek Elsayed, Elsayed; J. Schneider, Robert; Mostafa Mohamed, Mona
Inflammatory breast cancer (IBC) is a highly metastatic, aggressive, and fatal form of breast cancer. Patients presenting with IBC are characterized by a high number of axillary lymph node metastases. Recently, we found that IBC carcinoma tissues contain significantly higher levels of human cytomegalovirus (HCMV) DNA compared to other breast cancer tissues that may regulate cell signaling pathways. In fact, HCMV pathogenesis and clinical outcome can be statistically associated with multiple HCMV genotypes within IBC. Thus, in the present study, we established the incidence and types of HCMV genotypes present in carcinoma tissues of infected non-IBC versus IBC patients. We also assessed the correlation between detection of mixed genotypes of HCMV and disease progression. Genotyping of HCMV in carcinoma tissues revealed that glycoprotein B (gB)-1 and glycoprotein N (gN)-1 were the most prevalent HCMV genotypes in both non-IBC and IBC patients with no significant difference between patients groups. IBC carcinoma tissues, however, showed statistically significant higher incidence of detection of the gN-3b genotype compared to non-IBC patients. The incidence of detection of mixed genotypes of gB showed that gB-1 + gB-3 was statistically significantly higher in IBC than non-IBC patients. Similarly, the incidence of detection of mixed genotypes of gN showed that gN-1 + gN-3b and gN-3 + gN-4b/c were statistically significant higher in the carcinoma tissues of IBC than non-IBC. Mixed presence of different HCMV genotypes was found to be significantly correlated with the number of metastatic lymph nodes in non-IBC but not in IBC patients. In IBC, detection of mixed HCMV different genotypes significantly correlates with lymphovascular invasion and formation of dermal lymphatic emboli, which was not found in non-IBC patients.