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Keywords = oncoprotection

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13 pages, 624 KB  
Article
A Potential Oncoprotective Role of Cytomegalovirus Against Breast Cancer: Worldwide Correlation and Survey of Evidence
by Marko Jankovic, Sofija Glumac, Aleksandra Knezevic, Ana Tomic, Danijela Miljanovic, Jovana Cupic, Ana Banko, Djurdjina Kablar, Ivana Celic, Sara Urosevic and Ivana Lazarevic
Diseases 2025, 13(6), 181; https://doi.org/10.3390/diseases13060181 - 9 Jun 2025
Viewed by 1441
Abstract
Introduction: While not considered a genuine tumorigenic pathogen, the human cytomegalovirus (CMV) has been associated with a wide assortment of malignancies, including breast cancer (BC). In recent years, increasing evidence has been detailing the potential anti-oncogenic capabilities of CMV. Works in the literature [...] Read more.
Introduction: While not considered a genuine tumorigenic pathogen, the human cytomegalovirus (CMV) has been associated with a wide assortment of malignancies, including breast cancer (BC). In recent years, increasing evidence has been detailing the potential anti-oncogenic capabilities of CMV. Works in the literature addressing the issue are scarce, and a global approach elucidating the role of CMV in breast cancer is lacking. Aim: We inquired into the association between CMV and BC on a global level and surveyed the related literature. Material and Methods: Virus–tumor interaction was examined by correlating country-specific CMV seroprevalence and the age-standardized BC incidence rates for 73 countries, as provided by the International Agency for Research on Cancer (IARC). Statistical analysis was conducted using Spearman’s correlation, along with univariate and multivariate linear regression analysis. The literature review included works available in the PubMed® database until and including February 2025. Results: The worldwide incidence of BC correlated strongly and inversely with CMV prevalence the world over (p < 0.001, Spearman ρ = −0.553). This association was upheld after univariate and multivariate linear regression, extending to other tumors such as skin melanoma and kidney cancer (p < 0.001). Conclusions: In this study, we draw attention to a previously unexplored global inverse relationship between the prevalence of CMV and the incidence of BC, which suggests a potential oncoprotective role for this pathogen. Although the association itself does not imply causality, these data provide an intriguing possibility of observing CMV as a tentative factor of protection against this malignancy. Full article
(This article belongs to the Section Oncology)
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13 pages, 2366 KB  
Communication
Role of B Cells beyond Antibodies in HBV-Induced Oncogenesis: Fulminant Cancer in Common Variable Immunodeficiency—Clinical and Immunotransplant Implications with a Review of the Literature
by Przemyslaw Zdziarski and Andrzej Gamian
Diseases 2024, 12(5), 80; https://doi.org/10.3390/diseases12050080 - 23 Apr 2024
Viewed by 2604
Abstract
Although lymphoma is the most frequent malignancy in common variable immunodeficiency (CVID), solid tumors, especially affected by oncogenic viruses, are not considered. Furthermore, in vitro genetic studies and cell cultures are not adequate for immune system and HBV interaction. We adopted a previously [...] Read more.
Although lymphoma is the most frequent malignancy in common variable immunodeficiency (CVID), solid tumors, especially affected by oncogenic viruses, are not considered. Furthermore, in vitro genetic studies and cell cultures are not adequate for immune system and HBV interaction. We adopted a previously introduced clinical model of host–virus interaction (i.e., infectious process in immunodeficiency) for analysis of B cells and the specific IgG role (an observational study of a CVID patient who received intravenous immunoglobulin (IVIG). Suddenly, the patient deteriorated and a positive results of for HBs and HBV-DNA (369 × 106 copies) were detected. Despite lamivudine therapy and IVIG escalation (from 0.3 to 0.4 g/kg), CT showed an 11 cm intrahepatic tumor (hepatocellular carcinoma). Anti-HBs were positive in time-lapse analysis (range 111–220 IU/mL). Replacement therapy intensification was complicated by an immune complex disease with renal failure. Fulminant HCC in CVID and the development of a tumor as the first sign is of interest. Unfortunately, treatment with hepatitis B immune globulins (HBIG) plays a major role in posttransplant maintenance therapy. Anti-HB substitution has not been proven to be effective, oncoprotective, nor safe. Therefore, immunosuppression in HBV-infected recipients should be carefully minimized, and patient selection more precise with the exclusion of HBV-positive donors. Our clinical model showed an HCC pathway with important humoral host factors, contrary to epidemiological/cohort studies highlighting risk factors only (e.g., chronic hepatitis). The lack of cell cooperation as well as B cell deficiency observed in CVID play a crucial role in high HBV replication, especially in carcinogenesis. Full article
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14 pages, 1252 KB  
Article
Friend or Foe? Exploring the Role of Cytomegalovirus (HCMV) Infection in Head and Neck Tumors
by Aleksandar Trivic, Jovica Milovanovic, Djurdjina Kablar, Ana Tomic, Miljan Folic, Ana Jotic, Nada Tomanovic, Ana Marija Tomic, Igor Djoric and Marko Jankovic
Biomedicines 2024, 12(4), 872; https://doi.org/10.3390/biomedicines12040872 - 15 Apr 2024
Cited by 6 | Viewed by 3005
Abstract
Although not regarded as an oncogenic pathogen, the human cytomegalovirus (HCMV) has been associated with a wide array of malignancies. Conversely, a number of studies report on possible anti-tumor properties of the virus, apparently mediated via HCMV-galvanized T-cell tumor killing; these were recently [...] Read more.
Although not regarded as an oncogenic pathogen, the human cytomegalovirus (HCMV) has been associated with a wide array of malignancies. Conversely, a number of studies report on possible anti-tumor properties of the virus, apparently mediated via HCMV-galvanized T-cell tumor killing; these were recently being investigated in clinical trials for the purposes of anti-cancer treatment by means of dendritic cell vaccines and HCMV-specific cytotoxic T cells. In the present study, we have analyzed the relation between a complement of head-and-neck tumors and HCMV infection across 73 countries worldwide using Spearman correlation, univariate and multivariate regression analysis. Intriguingly, HCMV was found to be pro-oncogenic in patients with nasopharyngeal carcinoma; contrarywise, the virus manifested an inverse (i.e., anti-tumor) association with the tumors of the lip/oral region and the salivary glands. Although this putative protective effect was noted initially for thyroid neoplasia and hypopharyngeal tumors as well, after multivariate regression analysis the connection did not hold. There was no association between laryngeal cancer and HCMV infection. It would appear that, depending on the tissue, HCMV may exert both protective and oncogenic effects. The globally observed protective feature of the virus could potentially be utilized in future therapeutic approaches for salivary tumors and neoplasia in the lip/oral region. As correlation does not necessarily imply causation, more in-depth molecular analyses from comprehensive clinical studies are warranted to substantiate our findings. Full article
(This article belongs to the Special Issue Head and Neck Tumors, 3rd Edition)
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20 pages, 1040 KB  
Article
Human Cytomegalovirus Oncoprotection across Diverse Populations, Tumor Histologies, and Age Groups: The Relevance for Prospective Vaccinal Therapy
by Marko Jankovic, Tara Knezevic, Ana Tomic, Ognjen Milicevic, Tanja Jovanovic, Irena Djunic, Biljana Mihaljevic, Aleksandra Knezevic and Milena Todorovic-Balint
Int. J. Mol. Sci. 2024, 25(7), 3741; https://doi.org/10.3390/ijms25073741 - 27 Mar 2024
Cited by 4 | Viewed by 3307
Abstract
The oncogenicity of the human cytomegalovirus (CMV) is currently being widely debated. Most recently, mounting clinical evidence suggests an anti-cancer effect via CMV-induced T cell-mediated tumor destruction. However, the data were mostly obtained from single-center studies and in vitro experiments. Broad geographic coverage [...] Read more.
The oncogenicity of the human cytomegalovirus (CMV) is currently being widely debated. Most recently, mounting clinical evidence suggests an anti-cancer effect via CMV-induced T cell-mediated tumor destruction. However, the data were mostly obtained from single-center studies and in vitro experiments. Broad geographic coverage is required to offer a global perspective. Our study examined the correlation between country-specific CMV seroprevalence (across 73 countries) and the age-standardized incidence rate (of 34 invasive tumors). The populations studied were stratified according to decadal age periods as the immunologic effects of CMV seropositivity may depend upon age at initial infection. The International Agency for Research on Cancer of the World Health Organization (IARC WHO) database was used. The multivariate linear regression analysis revealed a worldwide inverse correlation between CMV seroprevalence and the incidences of 62.8% tumors. Notably, this inverse link persists for all cancers combined (Spearman’s ρ = −0.732, p < 0.001; β = −0.482, p < 0.001, adjusted R2 = 0.737). An antithetical and significant correlation was also observed in particular age groups for the vast majority of tumors. Our results corroborate the conclusions of previous studies and indicate that this oncopreventive phenomenon holds true on a global scale. It applies to a wide spectrum of cancer histologies, additionally supporting the idea of a common underlying mechanism—CMV-stimulated T cell tumor targeting. Although these results further advance the notion of CMV-based therapies, in-depth investigation of host–virus interactions is still warranted. Full article
(This article belongs to the Special Issue Pathogenesis and Immunology of Cytomegalovirus)
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19 pages, 1640 KB  
Article
Gut Microbiota, Metabolome, and Body Composition Signatures of Response to Therapy in Patients with Advanced Melanoma
by Giulia Vandoni, Federica D'Amico, Marco Fabbrini, Luigi Mariani, Sabina Sieri, Amanda Casirati, Lorenza Di Guardo, Michele Del Vecchio, Andrea Anichini, Roberta Mortarini, Francesco Sgambelluri, Giuseppe Celano, Nadia Serale, Maria De Angelis, Patrizia Brigidi, Cecilia Gavazzi and Silvia Turroni
Int. J. Mol. Sci. 2023, 24(14), 11611; https://doi.org/10.3390/ijms241411611 - 18 Jul 2023
Cited by 14 | Viewed by 3653
Abstract
Despite the recent breakthroughs in targeted and immunotherapy for melanoma, the overall survival rate remains low. In recent years, considerable attention has been paid to the gut microbiota and other modifiable patient factors (e.g., diet and body composition), though their role in influencing [...] Read more.
Despite the recent breakthroughs in targeted and immunotherapy for melanoma, the overall survival rate remains low. In recent years, considerable attention has been paid to the gut microbiota and other modifiable patient factors (e.g., diet and body composition), though their role in influencing therapeutic responses has yet to be defined. Here, we characterized a cohort of 31 patients with unresectable IIIC-IV-stage cutaneous melanoma prior to initiation of targeted or first-line immunotherapy via the following methods: (i) fecal microbiome and metabolome via 16S rRNA amplicon sequencing and gas chromatography/mass spectrometry, respectively, and (ii) anthropometry, body composition, nutritional status, physical activity, biochemical parameters, and immunoprofiling. According to our data, patients subsequently classified as responders were obese (i.e., with high body mass index and high levels of total, visceral, subcutaneous, and intramuscular adipose tissue), non-sarcopenic, and enriched in certain fecal taxa (e.g., Phascolarctobacterium) and metabolites (e.g., anethole), which were potentially endowed with immunostimulatory and oncoprotective activities. On the other hand, non-response was associated with increased proportions of Streptococcus, Actinomyces, Veillonella, Dorea, Fusobacterium, higher neutrophil levels (and a higher neutrophil-to-lymphocyte ratio), and higher fecal levels of butyric acid and its esters, which also correlated with decreased survival. This exploratory study provides an integrated list of potential early prognostic biomarkers that could improve the clinical management of patients with advanced melanoma, in particular by guiding the design of adjuvant therapeutic strategies to improve treatment response and support long-term health improvement. Full article
(This article belongs to the Special Issue Microbiota and Cancer 3.0)
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26 pages, 1556 KB  
Review
An Update on Tamoxifen and the Chemo-Preventive Potential of Vitamin E in Breast Cancer Management
by Farid Khallouki, Lhoussain Hajji, Somayya Saber, Toufik Bouddine, Mouad Edderkaoui, Mohammed Bourhia, Nora Mir, Adrian Lim, Adil El Midaoui, John P. Giesy, Mourad A. M. Aboul-Soud, Sandrine Silvente-Poirot and Marc Poirot
J. Pers. Med. 2023, 13(5), 754; https://doi.org/10.3390/jpm13050754 - 28 Apr 2023
Cited by 10 | Viewed by 7149
Abstract
Breast cancer (BC) is the most common female cancer in terms of incidence and mortality worldwide. Tamoxifen (Nolvadex) is a widely prescribed, oral anti-estrogen drug for the hormonal treatment of estrogen-receptor-positive BC, which represents 70% of all BC subtypes. This review assesses the [...] Read more.
Breast cancer (BC) is the most common female cancer in terms of incidence and mortality worldwide. Tamoxifen (Nolvadex) is a widely prescribed, oral anti-estrogen drug for the hormonal treatment of estrogen-receptor-positive BC, which represents 70% of all BC subtypes. This review assesses the current knowledge on the molecular pharmacology of tamoxifen in terms of its anticancer and chemo-preventive actions. Due to the importance of vitamin E compounds, which are widely taken as a supplementary dietary component, the review focuses only on the potential importance of vitamin E in BC chemo-prevention. The chemo-preventive and onco-protective effects of tamoxifen combined with the potential effects of vitamin E can alter the anticancer actions of tamoxifen. Therefore, methods involving an individually designed, nutritional intervention for patients with BC warrant further consideration. These data are of great importance for tamoxifen chemo-prevention strategies in future epidemiological studies. Full article
(This article belongs to the Special Issue New Knowledge and Challenges in Breast Cancer)
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15 pages, 2833 KB  
Article
Anticancer Effects of Propionic Acid Inducing Cell Death in Cervical Cancer Cells
by Chau Ha Pham, Joo-Eun Lee, Jinha Yu, Sung Hoon Lee, Kyung-Rok Yu, Jaewoo Hong, Namki Cho, Seil Kim, Dukjin Kang, Soojin Lee and Hee Min Yoo
Molecules 2021, 26(16), 4951; https://doi.org/10.3390/molecules26164951 - 16 Aug 2021
Cited by 42 | Viewed by 5891
Abstract
Recent studies found that short-chain fatty acids (SCFAs), which are produced through bacterial fermentation in the gastrointestinal tract, have oncoprotective effects against cervical cancer. The most common SCFAs that are well known include acetic acid, butyric acid, and propionic acid, among which propionic [...] Read more.
Recent studies found that short-chain fatty acids (SCFAs), which are produced through bacterial fermentation in the gastrointestinal tract, have oncoprotective effects against cervical cancer. The most common SCFAs that are well known include acetic acid, butyric acid, and propionic acid, among which propionic acid (PA) has been reported to induce apoptosis in HeLa cells. However, the mechanism in which SCFAs suppress HeLa cell viability remain poorly understood. Our study aims to provide a more detailed look into the mechanism of PA in HeLa cells. Flow cytometry analysis revealed that PA induces reactive oxygen species (ROS), leading to the dysfunction of the mitochondrial membrane. Moreover, PA inhibits NF-κB and AKT/mTOR signaling pathways and induces LC3B protein levels, resulting in autophagy. PA also increased the sub-G1 cell population that is characteristic of cell death. Therefore, the results of this study propose that PA inhibits HeLa cell viability through a mechanism mediated by the induction of autophagy. The study also suggests a new approach for cervical cancer therapeutics. Full article
(This article belongs to the Special Issue Biological Activity of Natural and Synthetic Compounds)
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16 pages, 1621 KB  
Communication
Cyst Reduction by Melatonin in a Novel Drosophila Model of Polycystic Kidney Disease
by Cassandra Millet-Boureima, Roman Rozencwaig, Felix Polyak and Chiara Gamberi
Molecules 2020, 25(22), 5477; https://doi.org/10.3390/molecules25225477 - 23 Nov 2020
Cited by 11 | Viewed by 9984
Abstract
Autosomal dominant polycystic kidney disease (ADPKD) causes progressive cystic degeneration of the renal tubules, the nephrons, eventually severely compromising kidney function. ADPKD is incurable, with half of the patients eventually needing renal replacement. Treatments for ADPKD patients are limited and new effective therapeutics [...] Read more.
Autosomal dominant polycystic kidney disease (ADPKD) causes progressive cystic degeneration of the renal tubules, the nephrons, eventually severely compromising kidney function. ADPKD is incurable, with half of the patients eventually needing renal replacement. Treatments for ADPKD patients are limited and new effective therapeutics are needed. Melatonin, a central metabolic regulator conserved across all life kingdoms, exhibits oncostatic and oncoprotective activity and no detected toxicity. Here, we used the Bicaudal C (BicC) Drosophila model of polycystic kidney disease to test the cyst-reducing potential of melatonin. Significant cyst reduction was found in the renal (Malpighian) tubules upon melatonin administration and suggest mechanistic sophistication. Similar to vertebrate PKD, the BicC fly PKD model responds to the antiproliferative drugs rapamycin and mimics of the second mitochondria-derived activator of caspases (Smac). Melatonin appears to be a new cyst-reducing molecule with attractive properties as a potential candidate for PKD treatment. Full article
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