Article
Cardiac & Cardiovascular Systems
Nicholas S. Wilcox, Seth J. Rotz, McKay Mullen, Evelyn J. Song, Betty Ky Hamilton, Javid Moslehi, Saro H. Armenian, Joseph C. Wu, June-Wha Rhee, Bonnie Ky
Summary: Sex-based differences exist in the prevalence and outcomes of cardiovascular disease and cancer. There may also be differences between males and females in the risk of cardiotoxicity following cancer therapy. However, for certain cancer treatments such as hormone therapy and immune therapy, sex-based differences have not been fully elucidated. Further research is needed to fill these knowledge gaps and guide future clinical practice.
CIRCULATION RESEARCH
(2022)
Article
Cardiac & Cardiovascular Systems
Husam Abdel-Qadir, Felicia Tai, Ruth Croxford, Peter C. Austin, Eitan Amir, Oscar Calvillo-Arguelles, Heather Ross, Douglas S. Lee, Paaladinesh Thavendiranathan
Summary: This study focused on the prognosis of heart failure (HF) in women who developed HF after receiving anthracyclines or trastuzumab for early stage breast cancer. The results showed that patients with cardiotoxic exposure had fewer comorbidities compared to age-matched controls, and those who developed HF after trastuzumab treatment had a better prognosis than HF controls.
CIRCULATION-HEART FAILURE
(2021)
Article
Biochemistry & Molecular Biology
Leonardo Schirone, Daniele Vecchio, Valentina Valenti, Maurizio Forte, Michela Relucenti, Annalisa Angelini, Tania Zaglia, Sonia Schiavon, Luca DAmbrosio, Gianmarco Sarto, Rosita Stanzione, Elisa Mangione, Selenia Miglietta, Anna Di Bona, Marny Fedrigo, Alessandra Ghigo, Francesco Versaci, Vincenzo Petrozza, Simona Marchitti, Speranza Rubattu, Massimo Volpe, Junichi Sadoshima, Luigi Frati, Giacomo Frati, Sebastiano Sciarretta
Summary: Heart failure is a common side effect of doxorubicin (DOX) treatment in cancer patients. This study aimed to investigate the role of the serine/threonine kinase MST1 in the development of DOX-induced heart failure. The results showed that MST1 signaling was activated in response to DOX treatment in mice and human myocardial tissue. Inhibition of MST1 attenuated DOX-induced cardiac dysfunction through the upregulation of SIRT3, a mitochondrial protection enzyme. These findings suggest that MST1 contributes to DOX-induced cardiomyopathy by downregulating SIRT3.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Review
Cardiac & Cardiovascular Systems
Jacqueline T. Vuong, Ashley F. Stein-Merlob, Richard K. Cheng, Eric H. Yang
Summary: Anthracyclines are important in the treatment of various cancers, but can have significant implications on cardiovascular health. As the number of cancer survivors increases, it becomes crucial to detect and treat anthracycline-induced cardiotoxicity. Current treatment methods are based on conventional heart failure treatment, but there is a need for specific therapies for anthracycline-induced cardiotoxicity.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
Article
Oncology
Julius C. C. Heemelaar, Steffie Heemelaar, Svenja N. N. Hertel, J. Wouter Jukema, Marieke Sueters, Marloes Louwerens, M. Louisa Antoni
Summary: This study examined the cardiac function of childhood cancer survivors with prior cardiotoxic treatment during pregnancy using echocardiographic parameters. The researchers found that the risk of left ventricular dysfunction (LVD) during pregnancy was low if the global longitudinal strain (GLS) at baseline was normal. The obstetric outcomes were comparable to the general population, except for patients who underwent abdominal irradiation, which had a high rate of preterm birth and miscarriage.
Review
Chemistry, Medicinal
Anastasia Stella Perpinia, Nikolaos Kadoglou, Maria Vardaka, Georgios Gkortzolidis, Apostolos Karavidas, Theodoros Marinakis, Chrysostomi Papachrysostomou, Panagiotis Makaronis, Charikleia Vlachou, Marina Mantzourani, Dimitrios Farmakis, Konstantinos Konstantopoulos
Summary: Modern treatment modalities in hematology have improved clinical outcomes of patients with hematological malignancies, but some anticancer drugs may have adverse effects on the cardiovascular system, leading to various cardiac disorders. Therefore, it is crucial to understand all aspects of cardiotoxicity and provide appropriate care promptly to patients.
Review
Pharmacology & Pharmacy
Konrad Teodor Sawicki, Valentina Sala, Lorenzo Prever, Emilio Hirsch, Hossein Ardehali, Alessandra Ghigo
Summary: Anthracyclines are essential in many cancer chemotherapy regimens, but their use is limited by dose-dependent cardiotoxicity. Despite over fifty years of research, the biological mechanisms underlying anthracycline cardiotoxicity remain incompletely understood. This review discusses the incidence, risk factors, types, and pathophysiology of anthracycline cardiotoxicity, along with methods for prevention and treatment, as well as recent advances in understanding the molecular mechanisms involved.
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, VOL 61, 2021
(2021)
Review
Medicine, Research & Experimental
Zahra Vaziri, Kiarash Saleki, Cena Aram, Parsa Alijanizadeh, Ramtin Pourahmad, Abbas Azadmehr, Naghmeh Ziaei
Summary: Cancer and cardiovascular disorders are leading causes of mortality worldwide. Chemotherapy-induced cardiotoxicity is a common adverse effect of cancer treatment. SGLT2 inhibitors, a class of antidiabetic drugs, have shown protective effects on the heart and body, reducing inflammation and improving cardiovascular risk factors. They can also regulate excessive inflammation, affecting neurological and cardiovascular disorders.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Review
Pediatrics
Claire Fraley, Sarah A. Milgrom, Lavanya Kondapalli, Matthew R. G. Taylor, Luisa Mestroni, Shelley D. Miyamoto
Summary: Cardiotoxicity is a well-recognized late effect among childhood cancer survivors, and understanding the mechanistic underpinnings is essential for prevention and treatment. This review explores the underlying mechanisms of cardiotoxicity, areas for prevention, and advancements in cardio-oncology involving human induced pluripotent stem cell cardiomyocytes and genetics.
Review
Oncology
Ainsley Ryan Yan Bin Lee, Chun En Yau, Chen Ee Low, Jiaqi Li, Sara Moiz Tyebally, Weiqin Lin, Li-Ling Tan, Chia-Te Liao, Wei-Ting Chang, Matilda Xinwei Lee, Chieh-Yang Koo, Ching-Hui Sia
Summary: This PRISMA-adherent systematic review and meta-analysis aims to evaluate the progression of cardiac dysfunction and levels of natriuretic peptides, and risk of heart failure in cancer patients receiving anthracyclines. The review found that there were no significant declines in cardiac function compared to after six months of treatment cessation. Approximately one in six patients experienced significant declines in LVEF.
Article
Oncology
Husam Abdel-Qadir, Rodrigo Carrasco, Peter C. Austin, Yue Chen, Limei Zhou, Jiming Fang, Henry M. H. Su, Iliana C. Lega, Padma Kaul, Tomas G. Neilan, Paaladinesh Thavendiranathan
Summary: A cohort study found that the use of SGLT2 inhibitors (SGLT2is) was associated with a reduced risk of hospitalization for heart failure after anthracycline-containing chemotherapy in elderly patients with diabetes. However, there was no significant difference in incident heart failure diagnosis or cardiovascular disease diagnosis.
JACC: CARDIOONCOLOGY
(2023)
Review
Biochemistry & Molecular Biology
A. C. Seara Fernando, Tais H. Kasai-Brunswick, H. M. Nascimento Jose, Antonio C. Campos-de-Carvalho
Summary: Anthracyclines are effective chemotherapeutic drugs for cancer treatment, but they can cause cardiotoxicity. Accumulation of senescent cardiac cells is an emerging mechanism associated with anthracycline-induced cardiotoxicity.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Review
Cardiac & Cardiovascular Systems
Willeke R. Naaktgeboren, David Binyam, Martijn M. Stuiver, Neil K. Aaronson, Arco J. Teske, Wim H. van Harten, Wim G. Groen, Anne M. May
Summary: Exercise may protect against doxorubicin-induced cardiotoxicity, especially shown in animal studies, potentially by reducing doxorubicin accumulation in cardiac tissue.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2021)
Review
Cardiac & Cardiovascular Systems
Armando Ferrera, Vincenzo Fiorentini, Simone Reale, Giorgio Solfanelli, Giacomo Tini, Emanuele Barbato, Massimo Volpe, Allegra Battistoni
Summary: Chemotherapies have significantly improved survival rates for cancer patients over the past 20 years, but their use can be limited by serious adverse effects. Anthracyclines, commonly used in the treatment of hematologic and solid cancers, may cause cardiac toxicity and lead to heart failure. This review explores the current evidence on anthracyclines' cardiotoxicity, including classifications, molecular mechanisms, and methods for diagnosis, treatment, and prevention. Effective management and care for patients receiving anthracycline treatment is crucial to prevent unnecessary discontinuation and improve cardiovascular outcomes in both the short and long term.
REVIEWS IN CARDIOVASCULAR MEDICINE
(2023)
Review
Health Care Sciences & Services
Roberto Rosenfeld, Silvia Riondino, Vincenzo Formica, Francesco Torino, Eugenio Martuscelli, Mario Roselli
Summary: Breast cancer is the most common type of cancer in women, and the chemotherapy drug doxorubicin can cause heart toxicity. Early diagnosis of heart toxicity is important to prevent complications. Non-coding RNA, specifically microRNA and circular RNA, are being researched as potential biomarkers for early detection. Further studies are needed to understand the mechanisms and develop reliable detection methods.
JOURNAL OF PERSONALIZED MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Josephine M. Jacoby, Silas Strakeljahn, Andreas Nitsch, Sander Bekeschus, Peter Hinz, Alexander Mustea, Axel Ekkernkamp, Mladen V. Tzvetkov, Lyubomir Haralambiev, Matthias B. Stope
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Article
Pharmacology & Pharmacy
Marleen J. Meyer, Alzbeta Tuerkova, Sarah Roemer, Christoph Wenzel, Tina Seitz, Jochen Gaedcke, Stefan Oswald, Juergen Brockmoeller, Barbara Zdrazil, Mladen Tzvetkov
DRUG METABOLISM AND DISPOSITION
(2020)
Article
Pharmacology & Pharmacy
Sarah Romer, Marleen J. Meyer, Kathrin Klein, Lennart V. Schneider, Johannes Matthaei, Ana Tzvetkova, Joanna Lapczuk-Romanska, Jochen Gaedcke, Marek Drozdzik, Jurgen Brockmoeller, Anne T. Nies, Mladen V. Tzvetkov
Summary: rs35854239 variant partially affects OCT1 splicing, leading to moderate changes in OCT1 expression in the human liver. The alternative spliced OCT1 transcript is not correctly localized in the plasma membrane and unable to transport substrates. However, this variant does not significantly impact the pharmacokinetics of drugs like sumatriptan and fenoterol.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Ole Jensen, Johannes Matthaei, Henry G. Klemp, Marleen J. Meyer, Jurgen Brockmoller, Mladen V. Tzvetkov
Summary: This study confirmed IBC as an endogenous biomarker of OCT1 activity in humans, with OCT1 potentially regulating cellular concentrations of specific regulators or co-substrates in lipid and energy metabolism. Unlike in mice, OCT1 in humans may not directly mediate the efflux of IBC, suggesting a different mechanism for the association between blood concentrations of carnitine derivatives and OCT1 genotype in humans.
FRONTIERS IN PHARMACOLOGY
(2021)
Editorial Material
Pharmacology & Pharmacy
Marleen J. Meyer, Mladen V. Tzvetkov
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Johannes Matthaei, Juergen Brockmoeller, Werner Steimer, Konstanze Pischa, Stefan Leucht, Maria Kullmann, Ole Jensen, Typhaine Ouethy, Mladen Vassilev Tzvetkov, Muhammad Rafehi
Summary: The pharmacokinetics of the tricyclic antidepressant amitriptyline is primarily influenced by the genotypes of CYP2D6 and CYP2C19, with OCT1 genetic variation playing a minor role. Inhibition of OCT1 by amitriptyline and nortriptyline in vitro was observed, but significant effects of OCT1 genetic polymorphism on drug pharmacokinetics were not found in clinical studies with healthy volunteers and depressive disorder patients.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biochemical Research Methods
Saskia Floerl, Annett Kuehne, Joachim Geyer, Juergen Brockmoeller, Mladen V. Tzvetkov, Yohannes Hagos
Summary: The study revealed a strong correlation in transport kinetics and inhibition pattern between human NTCP and mouse Ntcp, but specific compounds like benzbromarone showed significant species differences. Such differences need to be taken into consideration when transferring pharmacokinetic data from rodents to humans.
Article
Immunology
Eileen Moritz, Gabriele Jedlitschky, Josefine Negnal, Mladen Tzvetkov, Guenter Daum, Marcus Doerr, Stephan B. Felix, Henry Voelzke, Matthias Nauck, Edzard Schwedhelm, Peter Meisel, Thomas Kocher, Bernhard H. Rauch, Birte Holtfreter
Summary: The study found that S1P serum concentrations were significantly increased in patients with periodontitis and were correlated with high-sensitivity C-reactive protein levels. There was no significant association with caries variables, but the expression of the S1P-generating enzyme was elevated in inflamed gingival tissue compared to normal tissue.
JOURNAL OF INFLAMMATION RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Carolin Seifert, Ellen Balz, Susann Herzog, Anna Korolev, Sebastian Gassmann, Heiko Paland, Matthias A. Fink, Markus Grube, Sascha Marx, Gabriele Jedlitschky, Mladen Tzvetkov, Bernhard H. Rauch, Henry W. S. Schroeder, Sandra Bien-Moeller
Summary: Research has shown that PIM1 kinase plays a significant role in the behavior of glioblastoma stem cells, and its inhibition can lead to the death of these stem-like cells, suggesting a potential approach for glioblastoma therapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Medicine, General & Internal
Caspar Mewes, Tessa Alexander, Benedikt Buttner, Jose Hinz, Ayelet Alpert, Aron-F Popov, Tim Beissbarth, Mladen Tzvetkov, Marian Grade, Michael Quintel, Ingo Bergmann, Ashham Mansur
Summary: The study investigated the impact of the rs951818 SNP of the LAG-3 gene on sepsis mortality and disease severity. AA-homozygote patients had lower 28-day mortality and more often required invasive mechanical ventilation compared to C-allele carriers. The findings suggest genetic profiling of LAG-3 variants could be a promising approach for risk stratification in sepsis patients and personalized therapeutic targeting of immune checkpoints may be a future component of sepsis therapy.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Pharmacology & Pharmacy
Adrian Rump, Franziska N. Weiss, Louisa Schulz, Marie-Luise Kromrey, Eberhard Scheuch, Mladen V. Tzvetkov, Tyler White, Shane Durkee, Kevin W. Judge, Vincent Jannin, Aouatef Bellamine, Werner Weitschies, Michael Grimm
Summary: Controlling the timing and location of release of active ingredients in the gastrointestinal tract after oral administration remains a challenge. This study used MRI and salivary tracing techniques to investigate the impact of different combinations of capsule sizes and materials on the disintegration site and time. Results suggested that variability in the gastrointestinal localization of disintegration was lowest for the DUOCAP(R) capsule-in-capsule configuration using DRcaps(R) designed release capsules, enabling targeted delivery to the distal small intestine.
Article
Biochemistry & Molecular Biology
Marleen Julia Meyer, Simon Falk, Sarah Roemer, Clarissa Prinzinger, Sabine Tacke, Joachim Geyer, Stefan Simm, Mladen Vassilev Tzvetkov
Summary: In this study, the cloned dog OCT1 and OCT2 were compared to their human and mouse orthologs, revealing significant differences in transport kinetics. The functional characterization of dog OCT1 and OCT2 provides valuable insights for the use of dogs as pre-clinical models and for drug therapy in dogs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Marleen J. Meyer, Pascale C. F. Schreier, Mert Basaran, Stefaniia Vlasova, Tina Seitz, Juergen Brockmoeller, Barbara Zdrazil, Mladen V. Tzvetkov
Summary: This study analyzed the differences between human and mouse OCT1 orthologs and identified nonconserved amino acids Cys36 and Phe32 as determinants of OCT1 polyspecificity. It also found that the second phenol ring in Cys36 is essential for the affinity of fenoterol. This is the first study to report single amino acids as determinants of OCT1 polyspecificity.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Eik Schaefer, Christian Scheer, Karen Salje, Anja Fritz, Thomas Kohlmann, Nils-Olaf Huebner, Matthias Napp, Lizon Fiedler-Lacombe, Dana Stahl, Bernhard Rauch, Matthias Nauck, Uwe Voelker, Stephan Felix, Guglielmo Lucchese, Agnes Floeel, Stefan Engeli, Wolfgang Hoffmann, Klaus Hahnenkamp, Mladen Tzvetkov
Summary: In this study, we analyzed the symptoms and comorbidities of COVID-19 patients in North-East Germany and found that ageusia without anosmia was associated with the highest risk of hospitalization. Other symptoms such as dyspnea, vomiting, and fever were also significantly associated with increased hospitalization risk. Age > 60 years and comorbidities such as COPD, prior stroke, diabetes, kidney, and cardiac diseases were further identified as risk factors for hospitalization. These findings highlight the importance of considering both symptoms and comorbidities in identifying patients at high risk of hospitalization.
SCIENTIFIC REPORTS
(2022)
Article
Endocrinology & Metabolism
Angelique Kragl, Anke Hannemann, Matthias Nauck, Uwe Voelker, Heide Siggelkow, Alexander Teumer, Mladen V. Tzvetkov
Summary: Osteporosis is a chronic disease characterized by reduced bone mineral density and increased fracture risk. This study found significant associations between certain genetic variants and bone properties, supporting the role of genetic disposition in osteoporosis development. The study also identified a novel causal role of SCD expression in adipose tissue on bone integrity.
CALCIFIED TISSUE INTERNATIONAL
(2023)
