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https://www.readbyqxmd.com/read/28329187/bumped-kinase-inhibitors-for-therapy-of-cryptosporidiosis
#1
Matthew A Hulverson, Sumiti Vinayak, Ryan Choi, Deborah A Schaefer, Alejandro Castellanos-Gonzalez, Rama S R Vidadala, Carrie F Brooks, Gillian T Herbert, Dana P Betzer, Grant R Whitman, Hayley N Sparks, Samuel L M Arnold, Kasey L Rivas, Lynn K Barrett, A Clinton White, Maly Dustin J, Michael W Riggs, Boris Striepen, Wesley C Van Voorhis, Kayode K Ojo
Bumped kinase inhibitors (BKIs) of Cryptosporidium parvum calcium-dependent protein kinase 1 (CpCDPK1) are leading candidates for treatment of cryptosporidiosis diarrhea. Potential cardiotoxicity related to anti-human ether-à-go-go potassium channel (hERG) activity of the first generation anti-Cryptosporidium BKIs triggered further testing for efficacy. A luminescence assay adapted for high-throughput screening was used to measure inhibitory activities of BKIs on in vitro C. parvum. Furthermore, neonatal and interferon-γ knockout mouse models of C...
March 3, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28324265/cardiac-safety-efficacy-and-correlation-of-serial-serum-her2-extracellular-domain-shed-antigen-measurement-with-the-outcome-of-the-combined-trastuzumab-plus-cmf-in-women-with-her2-positive-metastatic-breast-cancer-results-from-the-eortc-10995-phase-ii-study
#2
Konstantinos Tryfonidis, S Marreaud, H Khaled, B De Valk, J Vermorken, M Welnicka-Jaskiewicz, K Aalders, J M S Bartlett, L Biganzoli, J Bogaerts, David Cameron
PURPOSE: Cardiotoxicity is a side effect of trastuzumab. We assessed efficacy and cardiac safety of CMF with trastuzumab (CMF+T) in HER2-positive metastatic breast cancer patients (MBC). METHODS: In this phase II study, centrally confirmed, previously treated HER2-positive MBC patients with measurable disease (per RECIST v 1.0) were enrolled. Initially, patients were randomized between 8 CMF cycles alone or combined with trastuzumab during chemotherapy, followed by 3-weekly trastuzumab maintenance till progression...
March 21, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28321239/xinfuli-improves-cardiac-function-histopathological-changes-and-attenuate-cardiomyocyte-apoptosis-in-rats-with-doxorubicin-induced-cardiotoxicity
#3
Pei-Pei Lu, Jie Ma, Xiao-Peng Liang, Cai-Xia Guo, Yan-Kun Yang, Kun-Qi Yang, Qi-Ming Shen, Li-Hong Ma, Xian-Liang Zhou
BACKGROUND: Xinfuli Granule (XG), a compound Chinese herbal medicine, has been effectively used in China for the treatment of heart failure for more than fifty years. This study aimed to investigate the effects and the underlying mechanisms of Xinfuli in rats with doxorubicin-induced cardiotoxicity. METHODS: Sprague-Dawley rats were treated with intraperitoneal injection of Doxorubicin (DOX, 2.5 mg/kg per week) for six weeks, and then randomly divided into four groups which received intragastrically administration of normal saline (control group) or different dosage of XG (0...
December 2016: Journal of Geriatric Cardiology: JGC
https://www.readbyqxmd.com/read/28320043/effects-of-ranolazine-in-a-model-of-doxorubicin-induced-left-ventricle-diastolic-dysfunction
#4
Donato Cappetta, Grazia Esposito, Raffaele Coppini, Elena Piegari, Rosa Russo, Loreta Pia Ciuffreda, Alessia Rivellino, Lorenzo Santini, Concetta Rafaniello, Cristina Scavone, Francesco Rossi, Liberato Berrino, Konrad Urbanek, Antonella De Angelis
BACKGROUND AND PURPOSE: Doxorubicin (DOXO) is a highly effective anticancer drug but its clinical application is impeded by cardiotoxicity. Asymptomatic diastolic dysfunction can be the earliest manifestation of DOXO cardiotoxicity. Therefore, a search for therapeutic intervention that can interfere with early manifestations and possibly prevent late cardiotoxicity is warranted. Increased DOXO-dependent reactive oxygen species may explain, in part, Ca(2+) and Na(+) overload that contributes to diastolic dysfunction and development of heart failure...
March 20, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28320040/mitochondria-as-a-target-for-the-cardioprotective-effects-of-cydonia-oblonga-mill-and-ficus-carica-l-in-doxorubicin-induced-cardiotoxicity
#5
Saman Gholami, Mir-Jamal Hosseini, Leila Jafari, Fatemeh Omidvar, Mohammad Kamalinejad, Vida Mashayekhi, Seyed Hojjat Hosseini, Azin Kardan, Jalal Pourahmad, Mohammad Reza Eskandari
Quince (Cydonia oblonga Mill.) and fig (Ficus carica L.) exhibit a broad spectrum of pharmacological activities. Regarding the cardiotoxic effect of doxorubicin (DOX) is mediated mainly through mitochondrial oxidative stress and dysfunction; the present study evaluated the cardioprotective effects of the aqueous extracts of Cydonia oblonga Mill. fruit (ACO) and Ficus carica L. fruit (AFC) against DOX-induced cardiotoxicity. Cardiomyocytes toxicity was induced in male Sprague Dawley rats by intraperitoneal (ip) injections of 2...
March 20, 2017: Drug Research
https://www.readbyqxmd.com/read/28316033/cardiovascular-complications-of-targeted-therapies-for-chronic-myeloid-leukemia
#6
REVIEW
Rongras Damrongwatanasuk, Michael G Fradley
The development of tyrosine kinase inhibitors (TKIs) dramatically changed the treatment landscape for many different cancers including chronic myeloid leukemia (CML). With the introduction of imatinib, the first TKI developed and approved to effectively treat CML, patient survival has increased dramatically and, in some cases, this fatal cancer can be managed as a chronic disease. Since the approval of imatinib in 2002, four additional TKIs have been developed to treat this disease including the second-generation TKIs nilotinib, dasatinib, and bosutinib and the third-generation TKI ponatinib...
April 2017: Current Treatment Options in Cardiovascular Medicine
https://www.readbyqxmd.com/read/28315715/sab-mediates-mitochondrial-dysfunction-involved-in-imatinib-mesylate-induced-cardiotoxicity
#7
Tara P Chambers, Luis Santiesteban, David Gomez, Jeremy W Chambers
Imatinib mesylate is an effective treatment for chronic myelogenous leukemia and gastrointestinal stromal tumors. Although imatinib mesylate is highly tolerable, it has been implicated in severe congestive heart failure in mouse models and patients. A hallmark of imatinib mesylate-induced cardiotoxicity is mitochondrial dysfunction. The mitochondrial scaffold Sab has been implicated in facilitating signaling responsible for mitochondrial dysfunction in a c-Jun N-terminal Kinase (JNK)-dependent manner. We examined the impact of Sab-mediated signaling on imatinib mesylate cardiotoxicity in H9c2 rat cardiomyocyte-like cells...
March 15, 2017: Toxicology
https://www.readbyqxmd.com/read/28315259/scutellarin-protects-against-doxorubicin-induced-acute-cardiotoxicity-and-regulates-its-accumulation-in-the-heart
#8
Xi-Peng Sun, Li-Li Wan, Quan-Jun Yang, Yan Huo, Yong-Long Han, Cheng Guo
The clinical use of doxorubicin (DOX) is limited by its dose-dependent cardiotoxicity. The present study investigated the effects of scutellarin against DOX-induced cardiotoxicity in rats using pharmacodynamic and pharmacokinetic approaches. DOX (20 mg/kg) was injected intraperitoneally (i.p.) as a single dose, and scutellarin (5 mg/kg/day) was injected intravenously (i.v.) for 3 days. Rats treated with DOX showed acute cardiotoxicity as indicated by the elevated serum lactate dehydrogenase (LDH) activity (4057...
March 17, 2017: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/28315122/cardio-oncology-the-nuclear-option
#9
REVIEW
Jorge A Alvarez, Raymond R Russell
PURPOSE OF REVIEW: Cardio-oncology focuses increased effort to decrease cancer treatment-related cardiotoxicity while continuing to improve outcomes. We sought to synthesize the latest in nuclear cardiology as it pertains to the assessment of left ventricular function in preventative guidelines and comparison to other modalities, novel molecular markers of pre-clinical cardiotoxicity, and its role in cardiac amyloid diagnosis. RECENT FINDINGS: Planar ERNA (equilibrium radionuclide angiocardiography) provides a reliable and proven means of monitoring and preventing anthracycline cardiotoxicity, and SPECT ERNA using solid-state gamma cameras may provide reproducible assessments of left ventricular function with reduced radiation exposure...
April 2017: Current Cardiology Reports
https://www.readbyqxmd.com/read/28314337/anticancer-treatments-and-cardiotoxicity-mechanisms-diagnostic-and-therapeutic-interventions-1st-edition
#10
(no author information available yet)
No abstract text is available yet for this article.
March 2017: Anticancer Research
https://www.readbyqxmd.com/read/28302530/regorafenib-overcomes-chemotherapeutic-multidrug-resistance-mediated-by-abcb1-transporter-in-colorectal-cancer-in-vitro-and-in-vivo-study
#11
Yi-Jun Wang, Yun-Kai Zhang, Guan-Nan Zhang, Sweilem B Al Rihani, Meng-Ning Wei, Pranav Gupta, Xiao-Yu Zhang, Suneet Shukla, Suresh V Ambudkar, Amal Kaddoumi, Zhi Shi, Zhe-Sheng Chen
Chemotherapeutic multidrug resistance (MDR) is a significant challenge to overcome in clinic practice. Several mechanisms contribute to MDR, one of which is the augmented drug efflux induced by the upregulation of ABCB1 in cancer cells. Regorafenib, a multikinase inhibitor targeting the RAS/RAF/MEK/ERK pathway, was approved by the FDA to treat metastatic colorectal cancer and gastrointestinal stromal tumors. We investigated whether and how regorafenib overcame MDR mediated by ABCB1. The results showed that regorafenib reversed the ABCB1-mediated MDR and increased the accumulation of [(3)H]-paclitaxel in ABCB1-overexpressing cells by suppressing efflux activity of ABCB1, but not altering expression level and localization of ABCB1...
March 13, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28300219/doxorubicin-induces-cardiotoxicity-through-upregulation-of-death-receptors-mediated-apoptosis-in-cardiomyocytes
#12
Liqun Zhao, Baolin Zhang
Doxorubicin is a highly effective anticancer agent but causes cardiotoxicity in many patients. The mechanisms of doxorubicin-induced cardiotoxicity remain incompletely understood. Here we investigated doxorubicin-induced cytotoxicity in human induced pluripotent stem cells-derived cardiomyocytes (iPS-CMs). We found that doxorubicin and related anthracycline agents (e.g., daunorubicin, idarubicin, and epirubicin) significantly upregulated the expression of death receptors (DRs) (TNFR1, Fas, DR4 and DR5) in iPS-derived cardiomyocytes at both protein and mRNA levels...
March 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28299613/cardiomyopathic-toxicity-from-chemotherapy-is-there-an-opportunity-for-preemptive-intervention
#13
REVIEW
Kristopher J Swiger, Jai Singh, Daniel J Lenihan
The fight against cancer has never appeared more optimistic with multiple ongoing advances in cancer therapeutics; however, the prevention of cardiotoxicity from these treatments, both old and new, is a major focus of recent research. We recommend conceptualizing the prevention of cardiotoxicity as binary whereby primary prevention involves a uniform application of preventative efforts to anyone receiving a potentially cardiotoxic drug and secondary prevention directed towards those with left ventricular dysfunction, whether symptomatic or not...
March 2017: Current Treatment Options in Cardiovascular Medicine
https://www.readbyqxmd.com/read/28298952/insights-for-oxidative-stress-and-mtor-signaling-in-myocardial-ischemia-reperfusion-injury-under-diabetes
#14
REVIEW
Dajun Zhao, Jian Yang, Lifang Yang
Diabetes mellitus (DM) displays a high morbidity. The diabetic heart is susceptible to myocardial ischemia/reperfusion (MI/R) injury. Impaired activation of prosurvival pathways, endoplasmic reticulum (ER) stress, increased basal oxidative state, and decreased antioxidant defense and autophagy may render diabetic hearts more vulnerable to MI/R injury. Oxidative stress and mTOR signaling crucially regulate cardiometabolism, affecting MI/R injury under diabetes. Producing reactive oxygen species (ROS) and reactive nitrogen species (RNS), uncoupling nitric oxide synthase (NOS), and disturbing the mitochondrial quality control may be three major mechanisms of oxidative stress...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28298705/cardiotoxicity-following-cancer-treatment
#15
REVIEW
G M Walls, A R Lyon, M T Harbinson, G G Hanna
More than half of those born after 1960 will develop cancer during their lifetime. Fortunately, owing to improved diagnosis and treatment, cure rates have risen steadily over the last three decades. With an increased survivorship, more will experience adverse effects of cancer therapeutics on the heart. As the oncologist's focus begins to encompass the issues of cancer survivorship, awareness of the management of cardiac toxicity would be prudent for all physicians looking after patients with cancer.
January 2017: Ulster Medical Journal
https://www.readbyqxmd.com/read/28295305/mitochondrial-ros-induced-erk1-2-activation-and-hsf2-mediated-at1-r-upregulation-are-required-for-doxorubicin-induced-cardiotoxicity
#16
Chih-Yang Huang, Jia-Yi Chen, Chia-Hua Kuo, Pei-Ying Pai, Tsung-Jung Ho, Tung-Sheng Chen, Fu-Jen Tsai, V Vijaya Padma, Wei-Wen Kuo, Chih-Yang Huang
Doxorubicin (DOX), one useful chemotherapeutic agent, is limited in clinical use because of its serious cardiotoxicity. Growing evidence suggests that angiotensin receptor blockers (ARBs) have cardioprotective effects in DOX-induced cardiomyopathy. However, the detailed mechanisms underlying the action of ARBs on the prevention of DOX-induced cardiomyocyte cell death have yet to be investigated. Our results showed that angiotensin II receptor type I (AT1 R) plays a critical role in DOX-induced cardiomyocyte apoptosis...
March 14, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28294073/alcohol-induced-hepato-cardiotoxicity-and-oxidative-damage-in-rats-the-protective-effect-of-n-butanol-extract-of-green-tea-camellia-sinensis-l-kuntze
#17
Amel Amrani, Nassima Boubekri, Soumia Lassad, Djamila Zama, Fadila Benayache, Samir Benayache
BACKGROUND: The principal aim of this study was to investigate the oxidative effects of acute alcohol consumption on the functions of the heart and the liver and the possible modification of this effect by Phenolic compounds from n-butanol extract of Camellia sinensis supplementation. METHOD: Three experimental groups of rats were used: control, ethanol-exposed (40% v/v, 5 g/kg per oral every 12 hours for 3 doses, binge model), and ethanol-exposed plus n-butanol extract of Camellia sinensis (100 mg/kg once a day for three days before and simultaneously with ethanol administration)...
March 9, 2017: Cardiovascular & Hematological Disorders Drug Targets
https://www.readbyqxmd.com/read/28290807/-cardiooncology-current-aspects-of-prevention-of-anthracycline-toxicity
#18
Y A Vasyuk, E L Shkolnik, V V Nesterov, L D Shkolnik, G V Varlan
Anthracyclines including doxorubicin, epirubicin, daunorubicin, aclarubicin are extensively used as chemotherapeutic agents for treatment of hematological and other malignancies. In cancer therapy anthracyclines are often used in combinations with other chemotherapeutic drugs and agents for molecularly targeted therapy. Anthracyclines are effective and powerful antineoplastic drugs with wide spectrum of application but active use of preparations of this group is limited because of such side effects as cardiotoxicity, myelotoxicity, thromboembolism, alopecia, etc...
December 2016: Kardiologiia
https://www.readbyqxmd.com/read/28288859/mitochondrial-toxicity-of-perfluorooctane-sulfonate-in-mouse-embryonic-stem-cell-derived-cardiomyocytes
#19
Lei-Lei Tang, Jia-Dan Wang, Ting-Ting Xu, Zhe Zhao, Jia-Jie Zheng, Ren-Shan Ge, Dan-Yan Zhu
Perfluorooctane sulfonate (PFOS) is a persistent organic contaminant that may cause cardiotoxicity in animals and humans. However, little is known about the underlying mechanism by which it affects the organelle toxicity in cardiomyocytes during the cardiogenesis. Our previous proteomic study showed that differences of protein expression mainly existed in mitochondria of cardiomyocytes differentiated from embryonic stem (ES) cells after exposure to PFOS. Here, we focused on mitochondrial toxicity of PFOS in ES cell-derived cardiomyocytes...
March 10, 2017: Toxicology
https://www.readbyqxmd.com/read/28287211/-anmco-aico-aiom-consensus-document-clinical-and-management-pathways-in-cardio-oncology
#20
Luigi Tarantini, Michele Massimo Gulizia, Andrea Di Lenarda, Nicola Maurea, Maurizio Giuseppe Abrignani, Irma Bisceglia, Daniella Bovelli, Luisa De Gennaro, Donatella Del Sindaco, Francesca Macera, Iris Parrini, Donatella Radini, Giulia Russo, Angela Beatrice Scardovi, Alessandro Inno
In Italy, cardiovascular diseases and cancer are the leading causes of death. Both diseases share the same risk factors and, having the highest incidence and prevalence in the elderly, they often coexist in the same individual. Furthermore, the enhanced survival of cancer patients registered in the last decades and linked to early diagnosis and improvement of care, not infrequently exposes them to the appearance of ominous cardiovascular complications due to the deleterious effects of cancer treatment on the heart and circulatory system...
January 2017: Giornale Italiano di Cardiologia
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