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- Geisler, J, et al.
(författare)
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A Review of the Potential Role of Human Cytomegalovirus (HCMV) Infections in Breast Cancer Carcinogenesis and Abnormal Immunity
- 2019
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 11:12
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Tidskriftsartikel (refereegranskat)abstract
- Previously recognized classical human onco-viruses can regulate complex neoplastic events, and are estimated to play a role during carcinogenesis in 15–20% of cancer cases. Although the DNA and gene products of several viruses have been found in breast tumors, none of the classical onco-viruses have definitely been linked to the initiation of breast cancer. However, recent evidence shows that human cytomegalovirus (HCMV) gene products are found in >90% of tumors and metastases of breast cancers, and their increased expression can be correlated to a more aggressive breast cancer phenotype. Supporting the active role of HCMV in breast cancer, a specific HCMV strain, HCMV-DB, was recently shown to exert oncogenic transformational activity in breast epithelial cells in vitro, and to give rise to fast-growing, triple-negative breast tumors when injected into immune deficient mice. The same observation holds true for clinical studies implying increased HCMV protein expression in triple negative breast cancer biopsies. In addition to functionally being able to hijack tumor-promoting cellular events, HCMV is known to exhibit a wide range of immunosuppressive effects, which can have radical impact on the tumor microenvironment. HCMV infected cells can avoid recognition and elimination by the immune system by orchestrating polarization of immunosuppressive type II macrophages, preventing antigen presentation, by expressing T cell inhibitory molecules, and possibly, by the induction of regulatory T (Treg) cell responses. These actions would be especially deleterious for the antigenic activation and proliferation of tumor specific CD8+ cytotoxic T lymphocytes (CTLs), whose effector functions have recently been targeted by successful, experimental immunotherapy protocols. The recognition of alternative causes and drivers of breast cancer is a pivotal research topic for the development of diagnostics and novel, effective preventive and therapeutic strategies targeting both tumor cells and their microenvironments.
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- Touma, J, et al.
(författare)
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Detection of Human Cytomegalovirus Proteins in Paraffin-Embedded Breast Cancer Tissue Specimens-A Novel, Automated Immunohistochemical Staining Protocol
- 2021
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Ingår i: Microorganisms. - : MDPI AG. - 2076-2607. ; 9:5
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Tidskriftsartikel (refereegranskat)abstract
- Emerging evidence supports a significant association between human cytomegalovirus (HCMV) and human malignancies, suggesting HCMV as a human oncomodulatory virus. HCMV gene products are found in >90% of breast cancer tumors and seem to be correlated with more aggressive disease. The definitive diagnosis of HCMV relies on identification of virus inclusions and/or viral proteins by different techniques including immunohistochemical staining. In order to reduce biases and improve clinical value of HCMV diagnostics in oncological pathology, automation of the procedure is needed and this was the purpose of this study. Tumor specimens from 115 patients treated for primary breast cancer at Akershus University Hospital in Norway were available for the validation of the staining method in this retrospective study. We demonstrate that our method is highly sensitive and delivers excellent reproducibility for staining of HCMV late antigen (LA), which makes this method useful for future routine diagnostics and scientific applications.
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- Touma, J, et al.
(författare)
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Human Cytomegalovirus Protein Expression Is Correlated with Shorter Overall Survival in Breast Cancer Patients: A Cohort Study
- 2023
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Ingår i: Viruses. - : MDPI AG. - 1999-4915. ; 15:3
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Tidskriftsartikel (refereegranskat)abstract
- Background: Human cytomegalovirus (HCMV) is increasingly suggested to be involved in human carcinogenesis and onco-modulation due to its ability to contribute to all hallmarks of cancer. Growing evidence demonstrates a link between HCMV infection and various malignancies, including breast cancer, which incidence and mortality are still on the rise. The etiology of breast cancer remains mostly unclear, leaving 80% of breast cancer cases considered to be sporadic. Identifying novel risk- and prognostic factors for improved breast cancer treatment and increased survival rates, were the objectives of this study. Methods: Automated immunohistochemical staining results for HCMV proteins in 109 breast tumors and lymph node metastasis were correlated with clinical follow-up data (>10 years). Statistical analyses for median Overall Survival (OS) were performed. Results: Survival analyses revealed shorter median OS for patients with HCMV-IE positive tumors of 118.4 months compared to 202.4 months for HCMV-IE negative tumors. A higher number of HCMV-LA positive cells in the tumors was also associated with a shorter OS in patients (146.2 months vs. 151.5 months). Conclusions: Our findings suggest a link between HCMV-infections and breast cancer prognosis, which paves the way for potential novel clinical intervention and targeted therapy that may prolong the overall survival of selected patients with breast cancer.
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