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https://www.readbyqxmd.com/read/28066861/the-incidence-of-cardiomyopathy-in-brca1-and-brca2-mutation-carriers-after-anthracycline-based-adjuvant-chemotherapy
#1
Edward J Pearson, Anju Nair, Yahya Daoud, Joanne L Blum
PURPOSE: Breast cancer remains the fourth-leading cause of death in the United States. Nearly 10% of breast cancers are hereditary, with deleterious mutations in BRCA1 and BRCA2 genes being the leading cause. Anthracycline chemotherapy, used commonly for breast cancer, carries cardiotoxicity risk. Recent studies demonstrated anthracycline-induced cardiac failure in homozygous BRCA2-deficient mice and increased rates of heart failure in homozygous BRCA1-deficient mice following ischemic insult...
January 9, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28057271/t-box-genes-in-human-development-and-disease
#2
T K Ghosh, J D Brook, A Wilsdon
T-box genes are important development regulators in vertebrates with specific patterns of expression and precise roles during embryogenesis. They encode transcription factors that regulate gene transcription, often in the early stages of development. The hallmark of this family of proteins is the presence of a conserved DNA binding motif, the "T-domain." Mutations in T-box genes can cause developmental disorders in humans, mostly due to functional deficiency of the relevant proteins. Recent studies have also highlighted the role of some T-box genes in cancer and in cardiomyopathy, extending their role in human disease...
2017: Current Topics in Developmental Biology
https://www.readbyqxmd.com/read/28056871/lung-adenocarcinoma-expressing-receptor-for-advanced-glycation-end-products-with-primary-systemic-al-amyloidosis-a-case-report-and-literature-review
#3
Shouichi Okamoto, Shinsaku Togo, Ichiro Nagata, Kazue Shimizu, Yoshika Koinuma, Yukiko Namba, Jun Ito, Toshimasa Uekusa, Kazuhisa Takahashi
BACKGROUND: Receptor for advanced glycation end-products (RAGE), a receptor for amyloids, is constitutively expressed in lungs and generally observed to be downregulated in lung cancer tissues. However, increasing levels of RAGE or serum amyloids is associated with poor outcome in lung cancer patients. We report a rare case of primary systemic amyloid light-chain (AL) amyloidosis in biopsy-proven multiple organs with early-stage non-small cell lung cancer (NSCLC) that displayed strong staining for RAGE in the tumour tissue...
January 5, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28052002/circulating-mir-1-as-a-potential-biomarker-of-doxorubicin-induced-cardiotoxicity-in-breast-cancer-patients
#4
Vagner Oliveira-Carvalho Rigaud, Ludmila R P Ferreira, Silvia M Ayub-Ferreira, Mônica S Ávila, Sara M G Brandão, Fátima D Cruz, Marília H H Santos, Cecilia B B V Cruz, Marco S L Alves, Victor S Issa, Guilherme V Guimarães, Edécio Cunha-Neto, Edimar A Bocchi
Cardiotoxicity is associated with the chronic use of doxorubicin leading to cardiomyopathy and heart failure. Identification of cardiotoxicity-specific miRNA biomarkers could provide clinicians with a valuable prognostic tool. The aim of the study was to evaluate circulating levels of miRNAs in breast cancer patients receiving doxorubicin treatment and to correlate with cardiac function. This is an ancillary study from "Carvedilol Effect on Chemotherapy-induced Cardiotoxicity" (CECCY trial), which included 56 female patients (49...
December 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/28039849/liquiritigenin-attenuates-cardiac-injury-induced-by-high-fructose-feeding-through-fibrosis-and-inflammation-suppression
#5
Xiong-Wei Xie
Diabetes combined with cardiomyopathy is considered as an essential complication, showing diastolic persistently and causing cardiac injury, which is linked to fibrosis progression and inflammation response. Fibrosis and inflammation response are two markers for cardiomyopathy. Liquiritigenin is a flavanone, isolated from Radix glycyrrhiza, which exhibits various biological properties, including anti-cancer and anti-inflammatory activities. Here, in our study, the protective effects and anti-inflammatory activity of liquiritigenin were explored in mice and cardiac muscle cells treated by fructose to reveal the possible mechanism by which liquiritigenin attenuates cardiac injury...
December 28, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28039505/factors-supporting-cardiomyopathy-screening-among-at-risk-adult-survivors-of-pediatric-malignancies
#6
Cheryl L Cox, Liang Zhu, Rohit P Ojha, Brenda D Steen, Susan Ogg, Leslie L Robison, Melissa M Hudson
PURPOSE: Anthracyclines and chest irradiation place adult survivors of childhood cancer at risk of cardiomyopathy; many survivors do not obtain the recommended screening. Based on our recent clinical trial, the addition of telephone counseling to a printed survivorship care plan more than doubled survivors' risk-based screening. Here, we sought to measure the impact of specific factors targeted in the intervention for their impact on survivors' screening participation. METHODS: Study population-survivors participating in a randomized longitudinal intervention trial...
December 30, 2016: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
https://www.readbyqxmd.com/read/28028033/interventions-for-preventing-cardiomyopathy-due-to-anthracyclines-a-bayesian-network-meta-analysis
#7
H Abdel-Qadir, G Ong, R Fazelzad, E Amir, D S Lee, P Thavendiranathan, G Tomlinson
BACKGROUND: The relative efficacy of interventions for primary prevention of anthracycline-associated cardiotoxicity is unknown. METHODS: We conducted a systematic review of randomized controlled trials for primary prevention of anthracycline-associated cardiotoxicity in adult cancer patients. We used hierarchal outcome definitions in the following order of priority: (1) composite of heart failure or decline in left ventricular ejection fraction, (2) decline in ejection fraction, or (3) heart failure...
December 26, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28011205/macrocyclic-mek1-2-inhibitor-with-efficacy-in-a-mouse-model-of-cardiomyopathy-caused-by-lamin-a-c-gene-mutation
#8
Wei Wu, Mahendra D Chordia, Barry P Hart, E Sathyajith Kumarasinghe, Min K Ji, Ajay Bhargava, Michael W Lawlor, Ji-Yeon Shin, Fusako Sera, Shunichi Homma, Antoine Muchir, Uday R Khire, Howard J Worman
Signaling mediated by extracellular signal-regulated kinases 1 and 2 (ERK1/2) is involved in numerous cellular processes. Mitogen-activated protein kinase kinases (MEK1/2) catalyze the phosphorylation of ERK1/2, converting it into an active kinase that regulates the expression of numerous genes and cellular processes. Inhibitors of MEK1/2 have demonstrated preclinical and clinical efficacy in certain cancers and types of cardiomyopathy. We report the synthesis of a novel, allosteric, macrocyclic MEK1/2 inhibitor that potently inhibits ERK1/2 activity in cultured cells and tissues of mice after systemic administration...
December 9, 2016: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/27988387/insights-into-the-role-of-maladaptive-hexosamine-biosynthesis-and-o-glcnacylation-in-development-of-diabetic-cardiac-complications
#9
Cheng Xue Qin, Rochelle Sleaby, Amy J Davidoff, James R Bell, Miles J De Blasio, Leanne M Delbridge, John C Chatham, Rebecca H Ritchie
Diabetes mellitus significantly increases the risk of heart failure, independent of coronary artery disease. The mechanisms implicated in the development of diabetic heart disease, commonly termed diabetic cardiomyopathy, are complex, but much of the impact of diabetes on the heart can be attributed to impaired glucose handling. It has been shown that the maladaptive nutrient-sensing hexosamine biosynthesis pathway (HBP) contributes to diabetic complications in many non-cardiac tissues. Glucose metabolism by the HBP leads to enzymatically-regulated, O-linked attachment of a sugar moiety molecule, β-N-acetylglucosamine (O-GlcNAc), to proteins, affecting their biological activity (similar to phosphorylation)...
December 14, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/27987485/design-synthesis-docking-and-qsar-study-of-substituted-benzimidazole-linked-oxadiazole-as-cytotoxic-agents-egfr-and-erbb2-receptor-inhibitors
#10
Md Jawaid Akhtar, Anees Ahmad Siddiqui, Ahsan Ahmed Khan, Zulphikar Ali, Rikeshwer Prasad Dewangan, Santosh Pasha, M Shahar Yar
The synthesis of benzimidazole linked oxadiazole derivatives designed as potential EGFR and erbB2 receptor inhibitors with anticancer and apoptotic activity were studied. Compounds 7a specifically inhibit EGFR and erbB2 receptor at 0.081 and 0.098 μM concentration. Some of the compounds showed strong, broad-spectrum antiproliferative activitiy when tested against five human cancer cell lines. Compounds 7a and 7n were more cytotoxic than 5-fluorouracil against MCF-7 cancer cell, with IC50 values of 5.0 and 2...
December 9, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27966803/yield-of-screening-echocardiograms-during-pediatric-follow-up-in-survivors-treated-with-anthracyclines-and-cardiotoxic-radiation
#11
Michael B Spewak, Rebecca S Williamson, Ann C Mertens, William L Border, Lillian R Meacham, Karen J Wasilewski-Masker
BACKGROUND: Guidelines published by the Children's Oncology Group recommend screening echocardiograms for childhood cancer survivors exposed to anthracyclines and/or cardiotoxic radiation. This study aims to assess risk factors for cardiac late effects while evaluating the overall yield of screening echocardiograms. PROCEDURE: Demographics, exposures, and echocardiogram results were abstracted from the medical records of survivors diagnosed at ≤ 21 years old and ≥ 2 years off therapy who were exposed to anthracyclines and/or potentially cardiotoxic radiotherapy...
December 14, 2016: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/27965861/exercise-to-prevent-anthrcycline-based-cardio-toxicity-exact-in-individuals-with-breast-or-hematological-cancers-a-feasibility-study-protocol
#12
Melanie R Keats, Scott A Grandy, Nicholas Giacomantonio, David MacDonald, Miroslaw Rajda, Tallal Younis
BACKGROUND: Anthracyclines (AC), widely used and effective anticancer agents, are known to induce both acute and chronic declines in cardiovascular health, ranging in severity from asymptomatic, subclinical dysfunction to substantial cardiomyopathy leading to congestive heart failure and death. There is substantial evidence that physical activity, higher levels of cardiorespiratory fitness, and exercise therapy can help prevent cardiovascular disease. Moreover, animal studies have shown that exercise performed concomitantly with AC treatment may attenuate early cardiac damage that results from AC exposure...
2016: Pilot and Feasibility Studies
https://www.readbyqxmd.com/read/27959443/an-epirubicin-peptide-conjugate-with-anticancer-activity-is-dependent-upon-the-expression-level-of-the-surface-transferrin-receptor
#13
Jiadan Yang, Qiyu Yang, Lu Xu, Jie Lou, Zhi Dong
Epirubicin (EPI) is one of the most widely used anticarcinogens; however, serious side effects, including cardiomyopathy and congestive heart failure, limit its long‑term administration. To overcome this problem, the HAIYPRH peptide ligand was used with EPI in the synthesis of a HAIYPRH‑EPI conjugate. The anticancer activity and cellular uptake of the conjugate were measured and evaluated. The results of the present study indicated that the cytotoxicity of HAIYPRH‑EPI was correlated with the expression of the cell surface transferrin receptor (TfR)...
January 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27933370/doxorubicin-induced-chronic-dilated-cardiomyopathy-the-apoptosis-hypothesis-revisited
#14
REVIEW
Cynthia Kankeu, Kylie Clarke, Egle Passante, Heinrich J Huber
The chemotherapeutic agent doxorubicin (DOX) has significantly increased survival rates of pediatric and adult cancer patients. However, 10% of pediatric cancer survivors will 10-20 years later develop severe dilated cardiomyopathy (DCM), whereby the exact molecular mechanisms of disease progression after this long latency time remain puzzling. We here revisit the hypothesis that elevated apoptosis signaling or its increased likelihood after DOX exposure can lead to an impairment of cardiac function and cause a cardiac dilation...
December 8, 2016: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/27931027/anthracycline-induced-cardiotoxicity-in-young-cancer-patients-the-role-of-carnitine
#15
Saro H Armenian
While the increased rates of survival in childhood cancers have increased progressively in recent decades, many childhood cancer survivors will have at least one chronic health condition within 40 years of age. In this regard, cardiovascular complications have emerged as a leading cause of long-term morbidity and mortality in long-term survivors of childhood cancer, likely due to exposure to anthracycline chemotherapy, and outcomes in patients with anthracycline-related cardiomyopathy remain poor. Some progress has been made in understanding the mechanisms at the basis of anthracycline-related cardiomyopathy, which appear to involve generation of reactive oxygen species, leading to mitochondrial dysfunction, followed by myocyte apoptosis and maladaptive left ventricular remodeling...
2016: Annals of Nutrition & Metabolism
https://www.readbyqxmd.com/read/27926950/c6-and-c7-substituted-3-4-dihydro-2-1h-quinolinones-as-inhibitors-of-monoamine-oxidase
#16
L Meiring, J Petzer, A Petzer
Purpose Monoamine oxidase (MAO) inhibitors are considered to be useful therapeutic agents and isoform specific inhibitors are employed for the treatment of depression and Parkinson's disease. MAO inhibitors are also under investigation for the treatment of disorders ranging from Alzheimer's disease, prostate cancer and certain cardiomyopathies. While a number of irreversible MAO inhibitors are available in the clinic, reversible inhibitors, particularly of the MAO-B isoform are still being developed. Based on our interest in discovering reversible inhibitors with specificity for MAO-B, we have recently reported that, among a series of 10 3,4-dihydro-2(1H)-quinolinone derivatives, are high potency MAO-B inhibitors, with a number of homologues displaying good selectivities for MAO-B over the MAO-A isoform...
December 7, 2016: Drug Research
https://www.readbyqxmd.com/read/27915987/sex-differences-in-alcohol-use-disorder
#17
Roberta Agabio, Claudia Pisanu, Gian Luigi Gessa, Flavia Franconi
BACKGROUND: Alcohol use disorder (AUD) is a common and disabling mental disorder associated with a significant burden of medical consequences and high socioeconomic costs. Although a growing number of studies support the existence of sex differences in several aspects of alcohol consumption and AUD, the majority of investigations have been conducted in men. OBJECTIVE: This article was aimed at reviewing sex differences in AUD, focusing on epidemiology, neurobiology, pharmacokinetics, susceptibility to medical consequences, and treatment...
December 1, 2016: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/27882103/identification-of-proteins-suppressing-the-functions-of-oncogenic-phosphatase-of-regenerating-liver-1-and-3
#18
Ju-Dong Lee, Haiyoung Jung, Sang-Hyun Min
The phosphatase of regenerating liver (PRL) family, including PRL-1, PRL-2, and PRL-3, comprises protein tyrosine phosphatases whose deregulation is associated with the tumorigenesis and metastasis of many types of cancer. However, the underlying mechanism is poorly understood. In this study, aiming to increase understanding of the molecular mechanisms underlying the functions of PRL-1 and PRL-3, a yeast two-hybrid system was employed to screen for their interacting proteins. Alignment with the NCBI BLAST database revealed 12 interactive proteins: Synaptic nuclear envelope protein 2, emerin, mannose 6-phosphate receptor-binding protein 1, low-density lipoprotein receptor-related protein 10, Rab acceptor 1, tumor protein D52-like 2, selectin P ligand (SELPLG), guanylate binding protein 1, transmembrane and ubiquitin-like domain-containing 2, NADH:ubiquinone oxidoreductase subunit B8, syndecan 4 and FK506-binding protein 8 (FKBP8)...
November 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/27858859/risk-factors-of-trastuzumab-induced-cardiotoxicity-in-breast-cancer-a-meta-analysis
#19
Zeeshan Jawa, Ruth M Perez, Lydia Garlie, Maharaj Singh, Rubina Qamar, Bijoy K Khandheria, Arshad Jahangir, Yang Shi
BACKGROUND: Trastuzumab targets the human epidermal growth factor receptor 2 oncogene and in combination with first-line therapy results in significantly improved survival outcomes and has thus become standard of care in both adjuvant and metastatic settings. While it is estimated that 1% to 4% of patients treated with trastuzumab will develop heart failure and ∼10% will experience a reduction in left ventricular ejection fraction (LVEF), the patient risk factors associated with trastuzumab-induced cardiotoxicity (TIC) are unclear...
November 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27855360/benzyloxynitrostyrene-analogues-a-novel-class-of-selective-and-highly-potent-inhibitors-of-monoamine-oxidase-b
#20
Mietha M Van der Walt, Gisella Terre'Blanche, Jacobus P Petzer, Anél Petzer
This study examines a series of novel 3-benzyloxy-β-nitrostyrene analogues as a novel class of inhibitors of the monoamine oxidase (MAO) enzymes. MAO inhibitors are considered useful for the treatment of depression and Parkinson's disease, and have recently attracted attention as potential therapeutic agents for a range of disorders including Alzheimer's disease, prostate cancer and certain cardiomyopathies. This study shows that the 3-benzyloxy-β-nitrostyrene analogues are potent inhibitors of the MAO-B isoform with IC50 values in the nanomolar range (39-565 nM)...
January 5, 2017: European Journal of Medicinal Chemistry
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