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  1. Article: Seasonal Pattern of Cerebrovascular Fatalities in Cancer Patients.

    Shivarov, Velizar / Shivarov, Hristo / Yordanov, Angel

    Healthcare (Basel, Switzerland)

    2023  Volume 11, Issue 4

    Abstract: Cancer patients are at increased risk of cerebrovascular events. The incidence of those events and the associated mortality are known to follow a seasonal pattern in the general population. However, it is unclear whether cerebrovascular mortality in ... ...

    Abstract Cancer patients are at increased risk of cerebrovascular events. The incidence of those events and the associated mortality are known to follow a seasonal pattern in the general population. However, it is unclear whether cerebrovascular mortality in cancer patients has seasonal variation. To address this question, we performed a retrospective analysis of the seasonality of deaths due to the fact of cerebrovascular diseases among patients with first primary malignancy registered between 1975 and 2016 in the SEER database. The presence of seasonality in death rates was modeled using the cosinor approach assuming a circa-annual pattern. A significant seasonal pattern with a peak in the first half of November was identified in all patient groups. The same peak was observed in almost all subgroups of patients defined based on demographic characteristics. However, not all entity-defined subgroups showed a seasonal pattern, which might be explained by the different pathologic processes affecting the circulatory system in each cancer type. Based on our findings, one can propose that the active monitoring of cancer patients for cerebrovascular events from the late autumn and during the winter can help in the reduction of mortality in this patient population.
    Language English
    Publishing date 2023-02-04
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2721009-1
    ISSN 2227-9032
    ISSN 2227-9032
    DOI 10.3390/healthcare11040456
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  2. Article ; Online: Dynamic trends in life expectancy and life years lost over five decades in patients from the SEER database with chronic myeloid leukaemia.

    Shivarov, Velizar / Grigorova, Denitsa

    British journal of haematology

    2022  Volume 198, Issue 2, Page(s) e23–e25

    MeSH term(s) Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/epidemiology ; Leukemia, Myeloid ; Life Expectancy
    Language English
    Publishing date 2022-04-12
    Publishing country England
    Document type Letter
    ZDB-ID 80077-6
    ISSN 1365-2141 ; 0007-1048
    ISSN (online) 1365-2141
    ISSN 0007-1048
    DOI 10.1111/bjh.18205
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  3. Article ; Online: Seasonality of Deaths Due to Heart Diseases among Cancer Patients.

    Shivarov, Velizar / Shivarov, Hristo / Yordanov, Angel

    Medicina (Kaunas, Lithuania)

    2022  Volume 58, Issue 11

    Abstract: Background and ... ...

    Abstract Background and Objectives
    MeSH term(s) Humans ; Retrospective Studies ; Heart Diseases/complications ; Cancer Survivors ; Pancreatic Neoplasms ; Leukemia
    Language English
    Publishing date 2022-11-15
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2188113-3
    ISSN 1648-9144 ; 1010-660X
    ISSN (online) 1648-9144
    ISSN 1010-660X
    DOI 10.3390/medicina58111651
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  4. Article: A Novel Two-Gene Expression-Based Prognostic Score in Malignant Pleural Mesothelioma.

    Shivarov, Velizar / Blazhev, Georgi / Yordanov, Angel

    Diagnostics (Basel, Switzerland)

    2023  Volume 13, Issue 9

    Abstract: Background: Malignant pleural mesothelioma (MPM) is a rare cancer type with an increasing incidence worldwide. We aimed to develop a rational gene expression-based prognostic score in MPM using publicly available datasets.: Methods: We developed and ... ...

    Abstract Background: Malignant pleural mesothelioma (MPM) is a rare cancer type with an increasing incidence worldwide. We aimed to develop a rational gene expression-based prognostic score in MPM using publicly available datasets.
    Methods: We developed and validated a two-gene prognostic score (2-PS) using three independent publicly available gene expression datasets. The 2-PS was built using the Robust Likelihood-Based Survival Modeling with Microarray Data method.
    Results: We narrowed down the model building to the analysis of 179 genes, which have been shown previously to be of importance to MPM development. Our statistical approach showed that a model including two genes (GOLT1B and MAD2L1) was the best predictor for overall survival (OS) (
    Conclusion: This is the first study to demonstrate good performance of only two-gene expression-based prognostic scores in MPM. Our initial approach for features selection allowed for an increased likelihood for the predictive value of the developed score, which we were also able to demonstrate.
    Language English
    Publishing date 2023-04-26
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2662336-5
    ISSN 2075-4418
    ISSN 2075-4418
    DOI 10.3390/diagnostics13091556
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  5. Article: Relative Risk of Death in Bulgarian Cancer Patients during the Initial Waves of the COVID-19 Pandemic.

    Shivarov, Velizar / Grigorova, Denitsa / Yordanov, Angel

    Healthcare (Basel, Switzerland)

    2023  Volume 11, Issue 18

    Abstract: Background: The COVID-19 pandemic has led to millions of documented deaths worldwide, with diverse distribution among countries. Surprisingly, Bulgaria, a middle-income European Union member state, ranked highest in COVID-19 mortality. This study aims ... ...

    Abstract Background: The COVID-19 pandemic has led to millions of documented deaths worldwide, with diverse distribution among countries. Surprisingly, Bulgaria, a middle-income European Union member state, ranked highest in COVID-19 mortality. This study aims to assess whether Bulgarian cancer patients experienced a higher relative risk (RR) of death compared to the general Bulgarian population during the pandemic.
    Materials and methods: Data from the Bulgarian National Statistical Institute and the Bulgarian National Cancer Registry were analyzed to estimate monthly RR of death in cancer patients compared to the general population before and during the first two years of the pandemic. The impact of the COVID-19 waves and predominant SARS-CoV-2 variants on RR was evaluated on various cancer types and age groups using a multiple linear regression approach.
    Results: During the COVID-19 waves, both the general population and cancer patients experienced a significant increase in mortality rates. Surprisingly, the RR of death in cancer patients was lower during pandemic waves. The results from the statistical modeling revealed a significant association between the COVID-19 waves and reduced RR for all cancer patients. Notably, the effect was more pronounced during waves associated with the Alpha and Delta variants. The results also showed varying impacts of the COVID-19 waves on RR when we analyzed subsamples of data grouped depending on the cancer type, age and sex.
    Conclusions: Despite increased overall mortality in Bulgarian cancer patients during the pandemic, the RR of death was lower compared to the Bulgarian general population, indicating that protective measures were relatively effective in this vulnerable group. This study underscores the importance of implementing and encouraging preventive measures, especially in cancer patients, to mitigate the impact of future viral pandemics and reduce excess mortality.
    Language English
    Publishing date 2023-09-20
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2721009-1
    ISSN 2227-9032
    ISSN 2227-9032
    DOI 10.3390/healthcare11182594
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  6. Article ; Online: The relevance of HLA class II genes in JAK2 V617F-positive myeloproliferative neoplasms.

    Shivarov, Velizar / Tsvetkova, Gergana / Hadjiev, Evgueniy / Ivanova, Milena

    Human immunology

    2023  Volume 84, Issue 3, Page(s) 199–207

    Abstract: In the present study we analyzed the relevance of HLA class II in JAK2 V617F-positive (JAK2 V617F+) myeloproliferative neoplasms (MPNs) focusing on genotype diversity, associations with specific alleles and haplotypes and the level of gene expression. ... ...

    Abstract In the present study we analyzed the relevance of HLA class II in JAK2 V617F-positive (JAK2 V617F+) myeloproliferative neoplasms (MPNs) focusing on genotype diversity, associations with specific alleles and haplotypes and the level of gene expression. One hundred and thirty-nine JAK2 V617F+ MPN patients and 1083 healthy controls, typed by Next generation sequencing (NGS) were included in the study. Multivariate generalized linear models with age as a covariate were applied for analysis of HLA-II allele and haplotype associations. Publicly available gene expression datasets were used to analyze HLA-II pathway genes expression in CD34+ stem cells (SCs) from MPN patients and healthy controls. We did not observe differences in HLA evolutionary divergence (HED) between JAK2 V617F+ MPNs and healthy controls. Two alleles: HLA-DPB1*03:01, DQB1*04:02 and 4 haplotypes: DPB1*02:01-DQA1*05:05-DQB1*03:01-DRB1*11:01, DPB1*04:02-DQA1*05:05-DQB1*03:01-DRB1*11:03, DPB1*02:01-DQA1*01:04-DQB1*05:03-DRB1*14:04, and DPB1*04:01-DQA1*03:01-DQB1*03:02-DRB1*04:01 had significantly lower frequency in MPN patients compared to controls. Additionally, we observed HLA-II alleles and haplotypes with statistically higher frequencies in JAK2 V617F+ patients. Differential gene expression analysis showed down-regulation of HLA-DRB1, -DRA, -DMA, -DMB, -DOA,-DRB4, CIITA, and CD74 genes in JAK2 V617F+ MPN CD34+ SCs as compared to normal CD34 + SCs. In conclusion, this study provides evidence for the pleiotropic effects of HLA-II genes in JAK2 V617F-driven MPNs.
    MeSH term(s) Humans ; Genes, MHC Class II ; Gene Frequency ; Neoplasms/genetics ; Genotype ; Haplotypes ; Alleles ; HLA-DRB1 Chains/genetics ; HLA-DQ beta-Chains/genetics ; Janus Kinase 2/genetics
    Chemical Substances HLA-DRB1 Chains ; HLA-DQ beta-Chains ; JAK2 protein, human (EC 2.7.10.2) ; Janus Kinase 2 (EC 2.7.10.2)
    Language English
    Publishing date 2023-01-26
    Publishing country United States
    Document type Journal Article
    ZDB-ID 801524-7
    ISSN 1879-1166 ; 0198-8859
    ISSN (online) 1879-1166
    ISSN 0198-8859
    DOI 10.1016/j.humimm.2023.01.006
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    ab Jg. 2022: Lesesaal (EG)

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  7. Article ; Online: Systematic analysis of copper, zinc, and selenium levels in JAK2 V617F-positive myeloproliferative neoplasms.

    Shivarov, Velizar / Tsvetkova, Gergana / Atanasova, Bisera / Genova, Mariana P / Ivanova, Irena / Hadjiev, Evgueniy / Ivanova, Milena

    Annals of hematology

    2024  

    Language English
    Publishing date 2024-01-17
    Publishing country Germany
    Document type Letter
    ZDB-ID 1064950-5
    ISSN 1432-0584 ; 0939-5555 ; 0945-8077
    ISSN (online) 1432-0584
    ISSN 0939-5555 ; 0945-8077
    DOI 10.1007/s00277-024-05624-z
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  8. Article ; Online: A Novel Two-Gene Expression-Based Prognostic Score in Malignant Pleural Mesothelioma

    Velizar Shivarov / Georgi Blazhev / Angel Yordanov

    Diagnostics, Vol 13, Iss 1556, p

    2023  Volume 1556

    Abstract: Background: Malignant pleural mesothelioma (MPM) is a rare cancer type with an increasing incidence worldwide. We aimed to develop a rational gene expression-based prognostic score in MPM using publicly available datasets. Methods: We developed and ... ...

    Abstract Background: Malignant pleural mesothelioma (MPM) is a rare cancer type with an increasing incidence worldwide. We aimed to develop a rational gene expression-based prognostic score in MPM using publicly available datasets. Methods: We developed and validated a two-gene prognostic score (2-PS) using three independent publicly available gene expression datasets. The 2-PS was built using the Robust Likelihood-Based Survival Modeling with Microarray Data method. Results: We narrowed down the model building to the analysis of 179 genes, which have been shown previously to be of importance to MPM development. Our statistical approach showed that a model including two genes (GOLT1B and MAD2L1) was the best predictor for overall survival (OS) ( p < 0.0001). The binary score based on the median of the continuous score stratified the patients into low and high score groups and also showed statistical significance in uni- and multivariate models. The 2-PS was validated using two independent transcriptomic datasets. Furthermore, gene set enrichment analysis using training and validation datasets showed that high score patients had distinct gene expression profiles. Our 2-PS also showed a correlation with the estimated infiltration by some immune cell fractions such as CD8+ T cells and M1/2 macrophages. Finally, 2-PS correlated with sensitivity or resistance to some commonly used chemotherapeutic drugs. Conclusion: This is the first study to demonstrate good performance of only two-gene expression-based prognostic scores in MPM. Our initial approach for features selection allowed for an increased likelihood for the predictive value of the developed score, which we were also able to demonstrate.
    Keywords gene expression ; prognosis ; prediction ; score ; mesothelioma ; Medicine (General) ; R5-920
    Subject code 616
    Language English
    Publishing date 2023-04-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: Possible impact of HLA class I and class II on malignancies driven by a single germ-line BRCA1 mutation.

    Ivanova, Milena / Ormandjieva, Anastasia / Dodova, Rumyana / Kaneva, Radka / Shivarov, Velizar

    International journal of immunogenetics

    2023  Volume 50, Issue 5, Page(s) 243–248

    Abstract: This study provides the first immunogenetic preliminary evidence that specific human leucocyte antigen (HLA) class I and class II alleles and haplotypes may be relevant for BRCA1 c.5263_5264insC driven oncogenesis. Observed HLA associations might have ... ...

    Abstract This study provides the first immunogenetic preliminary evidence that specific human leucocyte antigen (HLA) class I and class II alleles and haplotypes may be relevant for BRCA1 c.5263_5264insC driven oncogenesis. Observed HLA associations might have practical implications for establishment of predictive markers for the response to immunotherapies in malignancies driven by this germ-line mutation.
    MeSH term(s) Humans ; Histocompatibility Antigens Class I/genetics ; Haplotypes ; Germ-Line Mutation ; Neoplasms/genetics ; Alleles ; Histocompatibility Antigens Class II/genetics ; BRCA1 Protein/genetics
    Chemical Substances Histocompatibility Antigens Class I ; Histocompatibility Antigens Class II ; BRCA1 protein, human ; BRCA1 Protein
    Language English
    Publishing date 2023-07-28
    Publishing country England
    Document type Journal Article
    ZDB-ID 2177883-8
    ISSN 1744-313X ; 1744-3121
    ISSN (online) 1744-313X
    ISSN 1744-3121
    DOI 10.1111/iji.12631
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  10. Article ; Online: Bringing Together the Power of T Cell Receptor Mimic and Bispecific Antibodies for Cancer Immunotherapy: Still a Long Way to Go.

    Shivarov, Velizar / Blazhev, Georgi

    Monoclonal antibodies in immunodiagnosis and immunotherapy

    2021  Volume 40, Issue 2, Page(s) 81–85

    Abstract: Antibody-based cancer immunotherapy has revolutionized oncology. The first successful therapeutic antibodies relied on eliciting immune-mediated cytotoxicity (rituximab) or modulation of intracellular signaling (trastuzumab). Further attempts to enhance ... ...

    Abstract Antibody-based cancer immunotherapy has revolutionized oncology. The first successful therapeutic antibodies relied on eliciting immune-mediated cytotoxicity (rituximab) or modulation of intracellular signaling (trastuzumab). Further attempts to enhance the antitumor effects led to the development of immunoconjugates with radioactive or cytotoxic compounds (tositumomab, brentuximab vedotin). Another line of research led to the bispecific antibodies that can enhance the formation of immunological synapse between cancer and cytotoxic T cells (blinatumomab). Despite the constant advances in design and production, the application of monoclonal antibodies in cancer treatment remains limited by the presence of specific cell surface markers. A rational approach to target intracellular cancer antigens was proposed almost two decades ago by the development of anti-peptide human leukocyte antigen (HLA) complex (T cell receptor-like/mimic) antibodies. They could recognize specifically cancer neoantigens expressed in the context of specific HLA molecules theoretically providing unprecedented specificity. Furthermore, they can be developed in a semigeneric format, that is, to target common neoantigens expressed in the context of common HLA molecules. It is rationale to expect that the development of such antibodies in the format of bispecific antibody constructs can bring together the power of specific antibody-based recognition and that of T cell-mediated lysis. There are already some preliminary reports that suggest such constructs would be an achievable goal. In this brief review, we discuss some of the successful preclinical developments in the field and the major challenges that are yet to be addressed.
    MeSH term(s) Antibodies, Bispecific/immunology ; Antibodies, Bispecific/therapeutic use ; Antibodies, Monoclonal/immunology ; Antibodies, Monoclonal/therapeutic use ; Antineoplastic Agents, Immunological/therapeutic use ; Cytotoxicity, Immunologic/immunology ; Humans ; Immunoconjugates/therapeutic use ; Immunotherapy/trends ; Neoplasms/immunology ; Neoplasms/therapy ; Receptors, Antigen, T-Cell/immunology ; Receptors, Antigen, T-Cell/therapeutic use
    Chemical Substances Antibodies, Bispecific ; Antibodies, Monoclonal ; Antineoplastic Agents, Immunological ; Immunoconjugates ; Receptors, Antigen, T-Cell
    Language English
    Publishing date 2021-11-05
    Publishing country United States
    Document type Journal Article ; Review
    ISSN 2167-9436
    ISSN (online) 2167-9436
    DOI 10.1089/mab.2021.0003
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