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https://www.readbyqxmd.com/read/28336372/doxorubicin-targets-multiple-players-a-new-view-of-an-old-problem
#1
REVIEW
Donato Cappetta, Francesca Rossi, Elena Piegari, Federico Quaini, Liberato Berrino, Konrad Urbanek, Antonella De Angelis
Anthracycline cardiotoxicity remains a serious problem in paediatric and adult cancer survivors, and the advancement of cardio-oncology is a necessary step for an effective care of the patients that experience adverse cardiovascular effects. In this review, we discuss the multiple instruments used by clinicians that constitute the current strategies for primary and secondary prevention aiming at contrasting the onset of early and late doxorubicin-induced cardiotoxic events. The importance of early detection of cardiotoxicity and the following pharmacological therapy has been acknowledged with the emphasis put on impaired diastolic function, an increasingly recognized precocious sign of doxorubicin cardiotoxicity with an emerging scientific and clinical interest...
March 20, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28335887/trastuzumab-in-combination-with-weekly-paclitaxel-and-carboplatin-as-neo-adjuvant-treatment-for-her2-positive-breast-cancer-the-train-study
#2
Mette S van Ramshorst, Erik van Werkhoven, Ingrid A M Mandjes, Margaret Schot, Jelle Wesseling, Marie-Jeanne T F D Vrancken Peeters, Jetske M Meerum Terwogt, Monique E M Bos, Hendrika M Oosterkamp, Sjoerd Rodenhuis, Sabine C Linn, Gabe S Sonke
AIM: To determine the efficacy and safety of an anthracycline-free neo-adjuvant regimen consisting of weekly paclitaxel, carboplatin and trastuzumab in HER2-positive breast cancer. PATIENTS AND METHODS: Patients with stage II or III HER2-positive breast cancer received weekly paclitaxel ([P], 70 mg/m(2)), trastuzumab ([T], 2 mg/kg, loading dose 4 mg/kg) and carboplatin ([C], AUC = 3 mg ml(-1) min) for 24 weeks. In weeks 7, 8, 15, 16, 23 and 24, trastuzumab was administered without chemotherapy...
March 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28332451/inhibitory-effect-of-fruit-juices-on-the-doxorubicin-metabolizing-activity-of-carbonyl-reductase-1
#3
Takeshi Miura, Katsutoshi Nagai, Shingo Kaneshiro, Ayako Taketomi, Toshikatsu Nakabayashi, Hiroki Konishi, Toru Nishinaka, Tomoyuki Terada
BACKGROUND AND OBJECTIVE: Doxorubicin, an anthracycline anti-cancer drug, is effective for breast cancer and childhood lymphoma. Chronic cardiotoxicity has been known as a critical adverse effect of doxorubicin and is attributed to its metabolite doxorubicinol produced by carbonyl reductase 1 (CBR1, SDR21C1). Some flavonoids have been reported to act as inhibitors for CBR1, therefore, commercially available juices containing flavonoids are likely to be applicable as a prophylactic treatment against doxorubicin-induced cardiotoxicity by suppression doxorubicinol production...
March 9, 2017: Drug Metabolism Letters
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
#4
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/28315399/truncating-titin-ttn-variants-in-chemotherapy-induced-cardiomyopathy
#5
M Linschoten, A J Teske, A F Baas, A Vink, D Dooijes, H F Baars, F W Asselbergs
Chemotherapy-induced cardiomyopathy (CCMP) is a complication of chemotherapy treatment occurring in 9% of patients treated with anthracyclines. Currently, risk stratification is based on clinical risk factors that do not adequately explain the variable individual susceptibility. This points towards the presence of other determinants. In this case series, we describe two women with breast cancer that developed severe heart failure within months after chemotherapy. Genetic screening revealed truncating frameshift mutations in TTN, encoding the myofilament titin, in both women...
March 14, 2017: Journal of Cardiac Failure
https://www.readbyqxmd.com/read/28315122/cardio-oncology-the-nuclear-option
#6
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/28315068/efficacy-and-safety-of-nab-paclitaxel-125%C3%A2-mg-m-2-and-nab-paclitaxel-150%C3%A2-mg-m-2-compared-to-paclitaxel-in-early-high-risk-breast-cancer-results-from-the-neoadjuvant-randomized-geparsepto-study-gbg-69
#7
Jenny Furlanetto, Christian Jackisch, Michael Untch, Andreas Schneeweiss, Sabine Schmatloch, Bahriye Aktas, Carsten Denkert, Hermann Wiebringhaus, Sherko Kümmel, Mathias Warm, Stefan Paepke, Marianne Just, Claus Hanusch, John Hackmann, Jens Uwe Blohmer, Michael Clemens, Serban Dan Costa, Bernd Gerber, Valentina Nekljudova, Sibylle Loibl, Gunter von Minckwitz
PURPOSE: The GeparSepto study demonstrated that the use of nab-paclitaxel instead of paclitaxel prior to anthracycline-based chemotherapy could lead to a significantly increased pCR rate, especially in the triple negative subpopulation. We report efficacy and safety for patients treated with two different doses of nab-paclitaxel in comparison to weekly solvent-formulated paclitaxel. METHODS: Patients were treated for 12 weeks with either intravenous nab-paclitaxel 150 mg/m(2) (nP150) weekly, after study amendment 125 mg/m(2) (nP125) weekly or solvent-based paclitaxel 80 mg/m(2) (P80) weekly followed by epirubicin 90 mg/m(2) and cyclophosphamide 600 mg/m(2) on day 1 for four 3-week cycles...
March 17, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28306672/radiotherapy-chemotherapy-and-atherosclerosis
#8
San S Min, Anthony S Wierzbicki
PURPOSE OF REVIEW: This article reviews the effects of radiotherapy and chemotherapy in promoting the progression of atherosclerosis in patients with cancer. RECENT FINDINGS: Radiotherapy is associated with an increase in the incidence of atherosclerosis with the effects being related to the site of irradiation and dose of radiotherapy. Cranial irradiation is associated with dyslipidaemia and the metabolic syndrome secondary to effect on growth hormone secretion...
March 16, 2017: Current Opinion in Cardiology
https://www.readbyqxmd.com/read/28303646/quality-of-life-on-tsu-68-combination-of-docetaxel-and-tsu-68-an-oral-antiangiogenic-agent-in-patients-with-metastatic-breast-cancer-previously-treated-with-anthracycline
#9
Byeong Seok Sohn, Sung-Bae Kim, Jin-Hee Ahn, Kyung Hae Jung, Jeongeun Kim, Keun Seok Lee, Jungsil Ro, Seock-Ah Im, Young-Hyuck Im, Hong Suk Song, Hee Sook Park, Hyun-Cheol Chung
AIM: The aim of this study is to investigate whether the addition of TSU-68 would affect on the quality of life (QOL) of Korean metastatic breast cancer patients treated with docetaxel. METHODS: Sixty-three of 78 patients completed the baseline QOL questionnaires and at least one follow-up questionnaire comprising questions from the Korean Functional Assessment of Cancer Therapy-Breast (FACT-B), hospital anxiety and depression scale (HAD), the shortened form of the profile of mood states (BPOMS), and anticipation and anxiety for treatment scale...
March 16, 2017: Asia-Pacific Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28300219/doxorubicin-induces-cardiotoxicity-through-upregulation-of-death-receptors-mediated-apoptosis-in-cardiomyocytes
#10
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/28299197/new-insights-into-bacterial-type-ii-polyketide-biosynthesis
#11
REVIEW
Zhuan Zhang, Hai-Xue Pan, Gong-Li Tang
Bacterial aromatic polyketides, exemplified by anthracyclines, angucyclines, tetracyclines, and pentangular polyphenols, are a large family of natural products with diverse structures and biological activities and are usually biosynthesized by type II polyketide synthases (PKSs). Since the starting point of biosynthesis and combinatorial biosynthesis in 1984-1985, there has been a continuous effort to investigate the biosynthetic logic of aromatic polyketides owing to the urgent need of developing promising therapeutic candidates from these compounds...
2017: F1000Research
https://www.readbyqxmd.com/read/28291423/preclinical-evaluation-of-convection-enhanced-delivery-of-liposomal-doxorubicin-to-treat-pediatric-diffuse-intrinsic-pontine-glioma-and-thalamic-high-grade-glioma
#12
A Charlotte P Sewing, Tonny Lagerweij, Dannis G van Vuurden, Michaël H Meel, Susanna J E Veringa, Angel M Carcaboso, Pieter J Gaillard, W Peter Vandertop, Pieter Wesseling, David Noske, Gertjan J L Kaspers, Esther Hulleman
OBJECTIVE Pediatric high-grade gliomas (pHGGs) including diffuse intrinsic pontine gliomas (DIPGs) are primary brain tumors with high mortality and morbidity. Because of their poor brain penetrance, systemic chemotherapy regimens have failed to deliver satisfactory results; however, convection-enhanced delivery (CED) may be an alternative mode of drug delivery. Anthracyclines are potent chemotherapeutics that have been successfully delivered via CED in preclinical supratentorial glioma models. This study aims to assess the potency of anthracyclines against DIPG and pHGG cell lines in vitro and to evaluate the efficacy of CED with anthracyclines in orthotopic pontine and thalamic tumor models...
February 17, 2017: Journal of Neurosurgery. Pediatrics
https://www.readbyqxmd.com/read/28290834/-the-time-course-of-formation-of-systolic-dysfunction-of-the-heart-in-doxorubicin-cardiomyopathy
#13
V L Lakomkin, A A Abramov, V V Gramovich, O N Vyborov, E V Lukoshkova, V V Ermishkin, V I Kapelko
The anthracycline-induced cardiomyopathy is a frequent and menacing complication of antitumor therapy leading to chronic heart failure. A study of the formation of heart failure can reveal early signs of the development of systolic dysfunction of the heart. In this work in rats we studied cardiac function at different duration of doxorubicin treatment, the most effective anthracycline antibiotic. Cumulative doses of doxorubicin were 8-20 mg/kg, and the term of study lasted from 6 to 20 weeks. The echocardiography and catheterization of the left ventricle (LV) have been use...
January 2017: Kardiologiia
https://www.readbyqxmd.com/read/28290807/-cardiooncology-current-aspects-of-prevention-of-anthracycline-toxicity
#14
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/28290477/investigation-on-treatment-strategy-prognostic-factors-and-risk-factors-for-early-death-in-elderly-taiwanese-patients-with-diffuse-large-b-cell-lymphoma
#15
Shih-Feng Cho, Yi-Chang Liu, Hui-Hua Hsiao, Chiung-Tang Huang, Yu-Fen Tsai, Hui-Ching Wang, Sheng-Fung Lin, Ta-Chih Liu
This study aimed to investigate the treatment strategy, prognostic factors, and risk factors of early death in elderly patients (age ≥ 65 years) with diffuse large B-cell lymphoma (DLBCL) in the rituximab era. Data from elderly patients diagnosed with DLBCL between 2008 and 2014 were collected for analysis. Patients who were younger and had a better performance status were more likely to receive intensive frontline treatment. The median progression-free survival (PFS) and overall survival were 15 and 21 months, respectively...
March 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28290072/changes-in-brain-white-matter-integrity-after-systemic-treatment-for-breast-cancer-a-prospective-longitudinal-study
#16
Sanne Menning, Michiel B de Ruiter, Dick J Veltman, Willem Boogerd, Hester S A Oldenburg, Liesbeth Reneman, Sanne B Schagen
An increasing number of studies suggest chemotherapy for breast cancer may be neurotoxic. Cross-sectional MRI diffusion tensor imaging (DTI) studies suggest a vulnerability of brain white matter to various chemotherapeutic regimens. Up till now, this was confirmed in one prospective DTI study: Deprez et al. (2012) showed a widespread decline in fractional anisotropy (FA) of breast cancer patients after chemotherapy consisting of 5-fluorouracil (5-FU), epirubicin and cyclophosphamide (FEC) +/- taxanes +/- endocrine treatment...
March 13, 2017: Brain Imaging and Behavior
https://www.readbyqxmd.com/read/28285949/considerations-in-cardio-oncology-multiple-mobile-left-sided-cardiac-thrombi-in-chemotherapy-induced-cardiomyopathy
#17
Toshinori Minamishima, Kenichi Matsushita, Hiromu Morikubo, Aoi Isaka, Noriko Matsushita, Hidehito Endo, Hiroshi Kubota, Konomi Sakata, Toru Satoh, Hideaki Yoshino
With advances in cancer chemotherapy, the importance of the new clinical discipline of cardio-oncology, which is concerned with the cardiac effects of chemotherapy, is increasing. Herein we describe the case of a 48-year-old woman with a history of breast cancer who presented with symptoms of heart failure due to chemotherapy-induced cardiomyopathy. Treatment for the patient's breast cancer had included surgery and chemotherapy with anthracyclines and trastuzumab. Echocardiography revealed multiple mobile thrombi in the left ventricle and atrium...
March 10, 2017: Journal of Infection and Chemotherapy: Official Journal of the Japan Society of Chemotherapy
https://www.readbyqxmd.com/read/28285236/efficacy-of-nepa-netupitant-palonosetron-across-multiple-cycles-of-chemotherapy-in-breast-cancer-patients-a-subanalysis-from-two-phase-iii-trials
#18
Hope S Rugo, Giorgia Rossi, Giada Rizzi, Matti Aapro
OBJECTIVES: Breast cancer (BC) patients represent a high-risk population for experiencing chemotherapy-induced nausea and vomiting (CINV), since they frequently receive highly emetogenic anthracycline-cyclophosphamide-based (AC) chemotherapy, and are often female and young, two predisposing risk factors for CINV. Guidelines recommend the combination of a neurokinin-1 receptor antagonist (NK1RA), 5-hydroxytryptamine-3 RA (5-HT3RA), and dexamethasone (DEX) for CINV prophylaxis in AC-treated patients...
March 9, 2017: Breast: Official Journal of the European Society of Mastology
https://www.readbyqxmd.com/read/28283780/metabolic-carbonyl-reduction-of-anthracyclines-role-in-cardiotoxicity-and-cancer-resistance-reducing-enzymes-as-putative-targets-for-novel-cardioprotective-and-chemosensitizing-agents
#19
REVIEW
Kamil Piska, Paulina Koczurkiewicz, Adam Bucki, Katarzyna Wójcik-Pszczoła, Marcin Kołaczkowski, Elżbieta Pękala
Anthracycline antibiotics (ANT), such as doxorubicin or daunorubicin, are a class of anticancer drugs that are widely used in oncology. Although highly effective in cancer therapy, their usefulness is greatly limited by their cardiotoxicity. Possible mechanisms of ANT cardiotoxicity include their conversion to secondary alcohol metabolites (i.e. doxorubicinol, daunorubicinol) catalyzed by carbonyl reductases (CBR) and aldo-keto reductases (AKR). These metabolites are suspected to be more cardiotoxic than their parent compounds...
March 10, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28279423/alternative-biomarkers-for-combined-biology
#20
REVIEW
Yong-Hyun Kim, Jennifer Kirsop, Wai Hong Wilson Tang
Chemotherapy-related cardiac dysfunction (CRCD) has challenged clinicians to hesitate in using cardiotoxic agents such as anthracycline and several protein kinase inhibitors. As early detection of CRCD and timely cessation of cardiotoxic agents became a strategy to avoid CRCD, cardiac troponin and natriuretic peptide are measured to monitor cardiotoxicity; however, there are inconsistencies in their predictability of CRCD. Alternative biomarkers have been researched extensively for potential use as more sensitive and accurate biomarkers...
April 2017: Heart Failure Clinics
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