Category: Other Ion Pumps/Transporters

defined a preclinical model that recapitulates cell death and increased caspase 3/7 activation following sunitinib exposure 78

defined a preclinical model that recapitulates cell death and increased caspase 3/7 activation following sunitinib exposure 78. revolutionary model that can improve cardiotoxicity assessment toward precision medicine. Cardio\Oncology: A Rapidly Emerging Field The National Cancer Institute estimates that there is a 40% lifetime risk of developing cancer in the U.S. 2. Anticancer therapies have dramatically improved the outcomes of malignancy treatment over the past decades and the overall cancer death rate has declined by almost 25% since 1990 2. The demand for cardio\oncology services develops along with increasing cancer survivorship rates. However, cardiotoxicity\related adverse effects caused by these anticancer therapies are on the rise. The incidence of cardiotoxicity differs greatly between chemotherapeutic brokers, with pre\existing cardiovascular disease and other risk factors playing an important role in the development of cardiomyopathy secondary to malignancy treatment. Reported incidences of chemotherapy\induced cardiotoxicity vary based on how cardiotoxicity is usually defined, with the most commonly used definition derived from the Cardiac Review and Evaluation Committee (CREC) of trastuzumab\associated cardiotoxicity. The CREC characterizes myocardial toxicity by a symptomatic decrease in left ventricular ejection portion (LVEF) of at least 5%C55% or an asymptomatic decrease in LVEF of at least 10%C55% 3. N2,N2-Dimethylguanosine Additional variability in reported cardiotoxicity arises from differing baseline patient characteristics, follow\up occasions, and a lack of clinical trials reporting predefined cardiac endpoints for chemotherapeutic brokers. A comprehensive list of commonly used chemotherapeutic brokers, therapeutic indications, and cardiotoxicity rates compiled from relevant studies is usually presented in Table ?Table11 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33. Table 1 The most frequently used brokers in each chemotherapeutic class and their therapeutic indications, along with a range of reported cardiotoxicity rates for each agent for drug screening, you will find three key design elements to be consideredcell source, scaffold design, and biomolecules 61. In 2006, induced pluripotent stem cells (iPSCs) were established as a potential cell source by the innovative work of Takahashi et al. who used retrovirus\expressed transcription factors to reprogram somatic cells to iPSCs 62. You will find definite advantages of using iPSCs in tissue engineering as they have unlimited expansion capacity, can be derived from several, easily accessible cell types, and can be differentiated into multiple cell lineages. Efficient and chemically directed differentiation protocols have been developed to generate cardiomyocytes from iPSCs 63, which can be further subcategorized into atrial, ventricular, or nodal cells through patch\clamp analysis 64. Compared with animal models, hiPSC\CMs are more representative of human cardiac physiology in terms of ion channel expression, heart rate, and myofilament composition 65. Several studies exploring the cardiotoxicity of different chemotherapy brokers using stem cell models have been explained in the past few years 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78 (summarized in Table ?Table33). Table 3 This table outlines the key findings of each study that uses stem cell models to determine the cardiotoxic effects of different antineoplastic brokers transcriptomic response to varying doxorubicin doses that corresponded with cell damage and may be used to predict cardiotoxicity risk. 67 DoxorubicinDoxorubicin exhibited dose\related hiPSC\CM cell damage, changes in gene expression and electrophysiological abnormalities. CRISPR/Cas9 was used to show the association of TOP2B with doxorubicin\induced cardiotoxicity. 68 DoxorubicinThe downregulation of Qki5 in response to doxorubicin increased cardiomyocyte apoptosis. 69 DoxorubicinVascularized 3D tissue derived from hiPSC\CM exhibited different cardiotoxic responses in comparison to 2D models. 75 DoxorubicinDoxorubicin tested on hiPSC\CM\derived multiorgan\on\a\chip models revealed marked cardiotoxicity, with increased apoptosis, CK\MB levels, and visible arrhythmia. 76 Doxorubicin48\Hour doxorubicin treatment of a multiorgan\on\a\chip.Although cyclic stretch simulates ventricular filling, static stretch recreates embryonic development through progressive lengthening 66. stem cell\derived cardiomyocytes (hiPSC\CMs) and tissue engineering methods. These new technologies promise a revolutionary model that can improve cardiotoxicity assessment toward precision medicine. Cardio\Oncology: A Rapidly Emerging Field The National Cancer Institute estimates that there is a 40% lifetime risk of developing cancer in the U.S. 2. Anticancer therapies have dramatically improved the outcomes of malignancy treatment over the past decades and the overall cancer death rate has declined by almost 25% since 1990 2. The N2,N2-Dimethylguanosine demand for cardio\oncology services develops along with increasing cancer survivorship rates. However, cardiotoxicity\related adverse effects caused by these anticancer therapies are on the rise. The incidence of cardiotoxicity differs greatly between chemotherapeutic brokers, with pre\existing cardiovascular disease and other risk factors playing an important role in the development of cardiomyopathy secondary to malignancy treatment. Reported incidences of chemotherapy\induced cardiotoxicity vary based on how cardiotoxicity is usually defined, with the most commonly used definition derived from the Cardiac Review and Evaluation Committee (CREC) of trastuzumab\associated cardiotoxicity. The CREC characterizes myocardial toxicity by a symptomatic decrease in left ventricular ejection portion (LVEF) of at least 5%C55% or an asymptomatic decrease in LVEF of at least 10%C55% 3. Additional variability in reported cardiotoxicity arises from differing baseline patient characteristics, follow\up occasions, and a lack of clinical trials reporting predefined cardiac endpoints for chemotherapeutic brokers. A comprehensive list of commonly used chemotherapeutic brokers, therapeutic indications, and cardiotoxicity rates compiled from relevant studies is usually presented in Table ?Table11 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33. Table 1 The most frequently used brokers in each chemotherapeutic class and their therapeutic indications, along with a range of reported cardiotoxicity rates for each agent for drug screening, you will find three key design elements to be consideredcell source, scaffold design, and biomolecules 61. In 2006, induced pluripotent stem cells (iPSCs) were established as a potential cell source by the innovative work of Takahashi et al. who used retrovirus\expressed transcription factors to reprogram somatic cells to iPSCs 62. You will find definite advantages of using iPSCs in tissue engineering as they have unlimited expansion capacity, can be derived from several, easily accessible cell types, and can be differentiated into multiple cell lineages. Efficient and chemically directed differentiation protocols have been developed to generate cardiomyocytes from iPSCs 63, which can be further subcategorized into atrial, ventricular, or nodal cells through N2,N2-Dimethylguanosine patch\clamp analysis 64. Compared with animal models, hiPSC\CMs are more representative of human cardiac physiology in terms of ion channel expression, heart rate, and myofilament composition 65. Several studies TRIM39 exploring the cardiotoxicity of different chemotherapy brokers using stem cell models have been explained in the past few years 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78 (summarized in Table ?Table33). Table 3 This table outlines the key findings of each study that uses stem cell models to determine the cardiotoxic effects of different antineoplastic brokers transcriptomic response to varying doxorubicin doses that corresponded with cell damage and may be used to predict cardiotoxicity risk. 67 DoxorubicinDoxorubicin exhibited dose\related hiPSC\CM cell damage, changes in gene expression and electrophysiological abnormalities. CRISPR/Cas9 was used to show the association of TOP2B with doxorubicin\induced cardiotoxicity. 68 DoxorubicinThe downregulation of Qki5 in response to doxorubicin increased cardiomyocyte apoptosis. 69 DoxorubicinVascularized 3D tissue derived from hiPSC\CM exhibited.