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https://www.readbyqxmd.com/read/28314836/safe-heart-rationale-and-design-of-a-pilot-study-investigating-cardiac-safety-of-her2-targeted-therapy-in-patients-with-her2-positive-breast-cancer-and-reduced-left-ventricular-function
#1
Filipa Lynce, Ana Barac, Ming T Tan, Federico M Asch, Karen L Smith, Chau Dang, Claudine Isaacs, Sandra M Swain
BACKGROUND: Human epidermal growth receptor 2 (HER2) targeted therapies have survival benefit in adjuvant and metastatic HER2 positive breast cancer but are associated with cardiac dysfunction. Current U.S. Food and Drug Administration recommendations limit the use of HER2 targeted agents to patients with normal left ventricular (LV) systolic function. METHODS: The objective of the SAFE-HEaRt study is to evaluate the cardiac safety of HER2 targeted therapy in patients with HER2 positive breast cancer and mildly reduced left ventricular ejection fraction (LVEF) with optimized cardiac therapy...
March 17, 2017: Oncologist
https://www.readbyqxmd.com/read/28299613/cardiomyopathic-toxicity-from-chemotherapy-is-there-an-opportunity-for-preemptive-intervention
#2
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/28293802/history-of-hypertension-heart-disease-and-diabetes-and-ovarian-cancer-patient-survival-evidence-from-the-ovarian-cancer-association-consortium
#3
Albina N Minlikeeva, Jo L Freudenheim, Rikki A Cannioto, J Brian Szender, Kevin H Eng, Francesmary Modugno, Roberta B Ness, Michael J LaMonte, Grace Friel, Brahm H Segal, Kunle Odunsi, Paul Mayor, Emese Zsiros, Barbara Schmalfeldt, Rüdiger Klapdor, Thilo Dӧrk, Peter Hillemanns, Linda E Kelemen, Martin Kӧbel, Helen Steed, Anna de Fazio, Susan J Jordan, Christina M Nagle, Harvey A Risch, Mary Anne Rossing, Jennifer A Doherty, Marc T Goodman, Robert Edwards, Keitaro Matsuo, Mika Mizuno, Beth Y Karlan, Susanne K Kjær, Estrid Høgdall, Allan Jensen, Joellen M Schildkraut, Kathryn L Terry, Daniel W Cramer, Elisa V Bandera, Lisa E Paddock, Lambertus A Kiemeney, Leon F Massuger, Jolanta Kupryjanczyk, Andrew Berchuck, Jenny Chang-Claude, Brenda Diergaarde, Penelope M Webb, Kirsten B Moysich
PURPOSE: Survival following ovarian cancer diagnosis is generally low; understanding factors related to prognosis could be important to optimize treatment. The role of previously diagnosed comorbidities and use of medications for those conditions in relation to prognosis for ovarian cancer patients has not been studied extensively, particularly according to histological subtype. METHODS: Using pooled data from fifteen studies participating in the Ovarian Cancer Association Consortium, we examined the associations between history of hypertension, heart disease, diabetes, and medications taken for these conditions and overall survival (OS) and progression-free survival (PFS) among patients diagnosed with invasive epithelial ovarian carcinoma...
March 14, 2017: Cancer Causes & Control: CCC
https://www.readbyqxmd.com/read/28280600/structural-basis-of-a-novel-pd-l1-nanobody-for-immune-checkpoint-blockade
#4
Fei Zhang, Hudie Wei, Xiaoxiao Wang, Yu Bai, Pilin Wang, Jiawei Wu, Xiaoyong Jiang, Yugang Wang, Haiyan Cai, Ting Xu, Aiwu Zhou
The use of antibodies to target immune checkpoints, particularly PD-1/PD-L1, has made a profound impact in the field of cancer immunotherapy. Here, we identified KN035, an anti-PD-L1 nanobody that can strongly induce T-cell responses and inhibit tumor growth. The crystal structures of KN035 complexed with PD-L1 and free PD-L1, solved here at 1.7 and 2.7 Å resolution, respectively, show that KN035 competes with PD-1 (programmed death protein 1) for the same flat surface on PD-L1, mainly through a single surface loop of 21 amino acids...
2017: Cell Discovery
https://www.readbyqxmd.com/read/28260499/regulatory-role-of-g-protein-coupled-receptors-in-pancreatic-cancer-development-and-progression
#5
Hildegard M Schuller
BACKGROUND: Pancreatic cancer is the fourth leading cause of cancer deaths with incidence rising and a high mortality rate. Smoking, psychological stress, diabetes, pancreatitis and alcohol abuse are known risk factors for pancreatic cancer. OBJECTIVE: Targeting G protein-coupled receptor signaling for the prevention and therapy of pancreatic cancer. METHOD: Review of published literature. RESULTS AND CONCLUSION: All known risk factors for pancreatic cancer cause hyperactive cyclic adenosine monophosphate (cAMP) signaling via cancer stimulating Gαs-coupled beta-adrenergic and prostaglandin E2 receptors and/or by suppressing signaling via inhibitory Gαi-coupled GABAB-receptors...
March 3, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28222734/diabetes-and-beta-adrenergic-blockage-are-risk-factors-for-metastatic-prostate-cancer
#6
Malte Krönig, Christian Haverkamp, Antonia Schulte, Laura Heinicke, Kathrin Schaal, Vanessa Drendel, Martin Werner, Ulrich Wetterauer, Wolfgang Schultze-Seemann, Cordula Annette Jilg
BACKGROUND: We evaluated the influence of comorbidity inferred risks for lymph node metastasis (pN1) and positive surgical margins (R1) after radical prostatectomy in order to optimize pretherapeutic risk classification. We analyzed 454 patients after radical prostatectomy (RP) between 2009 and 2014. Comorbidities were defined by patients' medication from our electronic patient chart and stratified according to the ATC WHO code. Endpoints were lymph node metastasis (pN1) and positive surgical margins (R1)...
February 21, 2017: World Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28185035/anthracycline-chemotherapy-and-cardiotoxicity
#7
REVIEW
John V McGowan, Robin Chung, Angshuman Maulik, Izabela Piotrowska, J Malcolm Walker, Derek M Yellon
Anthracycline chemotherapy maintains a prominent role in treating many forms of cancer. Cardiotoxic side effects limit their dosing and improved cancer outcomes expose the cancer survivor to increased cardiovascular morbidity and mortality. The basic mechanisms of cardiotoxicity may involve direct pathways for reactive oxygen species generation and topoisomerase 2 as well as other indirect pathways. Cardioprotective treatments are few and those that have been examined include renin angiotensin system blockade, beta blockers, or the iron chelator dexrazoxane...
February 2017: Cardiovascular Drugs and Therapy
https://www.readbyqxmd.com/read/28178210/perindopril-induces-tsp-1-expression-in-hypertensive-patients-with-endothelial-dysfunction-in-chronic-treatment
#8
Valentina Buda, Minodora Andor, Lucian Petrescu, Carmen Cristescu, Dana Emilia Baibata, Mirela Voicu, Melania Munteanu, Ioana Citu, Calin Muntean, Octavian Cretu, Mirela Cleopatra Tomescu
Thrombospondin-1 (TSP-1) is a potent endogenous inhibitor of both physiological and pathological angiogenesis, widely studied as a target in drug development for treating cancer. Several studies performed in the cardiovascular field on TSP-1 are contradictory, the role of TSP-1 in the physiopathology of cardiovascular disorders (CVDs) being, for the moment, incompletely understood and may be due to the presence of several domains in its structure which can stimulate many cellular receptors. It has been reported to inhibit NO-mediated signaling and to act on the angiogenesis, tissue perfusion, endothelial cell proliferation, and homeostasis, so we aimed to quantify the effect Perindopril has on TSP-1 plasma levels in hypertensive patients with endothelial dysfunction in comparison with other antihypertensive drugs, such as beta blockers, calcium channel blockers, and diuretics, in a chronic treatment...
February 7, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28132057/is-beta-blocker-use-beneficial-in-breast-cancer-a-meta-analysis
#9
Hyun Yul Kim, Youn Joo Jung, Sang Hyup Lee, Hyuk Jae Jung, Kyoungjune Pak
OBJECTIVE: Preclinical studies have proved that beta-blocking agents inhibit several pathways for breast cancer progression and metastasis. We aimed to evaluate the association between beta-blocker use and prognosis of breast cancer. METHODS: A systematic search for studies from MEDLINE and EMBASE (inception to March 2014) was performed using the keywords "breast cancer" and "beta-blocker." In 2 groups of breast cancer patients (beta-blocker users and non-beta-blocker users), overall deaths (ODs), cancer-specific deaths (CSDs), and recurrences were compared...
January 28, 2017: Oncology
https://www.readbyqxmd.com/read/28123076/cardiovascular-disease-in-cancer-survivors
#10
REVIEW
Tochi M Okwuosa, Sarah Anzevino, Ruta Rao
Certain cancer therapies, including radiation therapy and some types of chemotherapies, are associated with increased risk of cardiovascular disease (CVD) and events. Some of these effects such as those presented by anthracyclines, radiation therapy, cisplatin, as well as those presented by hormone therapy for breast cancer-usually taken for many years for some breast and prostate cancers-are long-lasting and associated with cardiovascular events risk more than 20 years after cancer treatment. Cardiovascular testing, diagnostic assessment of suspected cardiovascular symptomatology, as well as laboratory tests for CVD risk factors are imperative...
February 2017: Postgraduate Medical Journal
https://www.readbyqxmd.com/read/28101033/maximizing-the-benefit-cost-ratio-of-anthracyclines-in-metastatic-breast-cancer-case-report-of-a-patient-with-a-complete-response-to-high-dose-doxorubicin
#11
Kevin Shee, Alan T Kono, Susan P D'Anna, Mark A Seltzer, Xiaoying Lu, Todd W Miller, Mary D Chamberlin
Despite the clinical efficacy of anthracycline agents such as doxorubicin, dose-limiting cardiac toxicities significantly limit their long-term use. Here, we present the case of a 33-year-old female patient with extensive metastatic ER+/PR+/HER2- mucinous adenocarcinoma of the breast, who was started on doxorubicin/cyclophosphamide therapy after progressing on paclitaxel and ovarian suppressor goserelin with aromatase inhibitor exemestane. The patient was comanaged by cardiology, who carefully monitored measures of cardiac function, including EKGs, serial echocardiograms, and profiling of lipids, troponin, and pro-BNP every 2 months...
September 2016: Case Reports in Oncology
https://www.readbyqxmd.com/read/28031536/use-of-non-selective-%C3%AE-blockers-is-associated-with-decreased-tumor-proliferative-indices-in-early-stage-breast-cancer
#12
Alexa Montoya, Clarissa N Amaya, Andres Belmont, Nabih Diab, Richard Trevino, Geri Villanueva, Steven Rains, Luis A Sanchez, Nabeel Badri, Salman Otoukesh, Ali Khammanivong, Danielle Liss, Sarah T Baca, Renato J Aguilera, Erin B Dickerson, Alireza Torabi, Alok K Dwivedi, Aamer Abbas, Karinn Chambers, Brad A Bryan, Zeina Nahleh
Previous studies suggest beta-adrenergic receptor (β-AR) antagonists (β-blockers) decrease breast cancer progression, tumor metastasis, and patient mortality; however the mechanism for this is unknown. Immunohistochemical analysis of normal and malignant breast tissue revealed overexpression of β1-AR and β3-AR in breast cancer. A retrospective cross-sectional study of 404 breast cancer patients was performed to determine the effect of β-blocker usage on tumor proliferation. Our analysis revealed that non-selective β-blockers, but not selective β-blockers, reduced tumor proliferation by 66% (p < 0...
January 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28028033/interventions-for-preventing-cardiomyopathy-due-to-anthracyclines-a-bayesian-network-meta-analysis
#13
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/27957711/the-role-of-beta-blockers-in-the-treatment-of-hypertension
#14
John M Cruickshank
IMPORTANCE: Two major guide-line committees (JNC-8 and NICE UK) have dropped beta-blockers as first-line therapy in the treatment of hypertension. Also, recent meta-analyses (that do not take age into account) have concluded that beta-blockers are inappropriate first-line agents in the treatment of hypertension. This review seeks to shed some light on the "rights and wrongs" of such actions and conclusions. OBJECTIVES: Because the pathophysiology of primary/essential hypertension differs in elderly and younger subjects, the latter being closely linked to obesity and increased sympathetic nerve activity, the author sought to clarify the efficacy of beta-blockers in the younger/middle-aged group in reducing the risk of death, and cardiovascular end-points...
December 13, 2016: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/27910284/resting-heart-rate-is-an-independent-predictor-of-death-in-patients-with-colorectal-pancreatic-and-non-small-cell-lung-cancer-results-of-a-prospective-cardiovascular-long-term-study
#15
Markus S Anker, Nicole Ebner, Bert Hildebrandt, Jochen Springer, Marianne Sinn, Hanno Riess, Stefan D Anker, Ulf Landmesser, Wilhelm Haverkamp, Stephan von Haehling
AIMS: Patients with advanced cancer have been shown to suffer from abnormal cardiac function and impaired exercise capacity that may contribute to their impaired quality of life. As tachycardia is considered as a sign of potential early cardiac damage, we sought to determine whether resting heart rate and other ECG-derived variables have prognostic value. METHODS AND RESULTS: From 2005 to 2010, we enrolled 145 patients with histologically confirmed cancer (36 colorectal, 72 pancreatic, and 37 non-small cell lung cancer patients) and 59 healthy controls...
December 2016: European Journal of Heart Failure
https://www.readbyqxmd.com/read/27906047/propranolol-and-survival-from-breast-cancer-a-pooled-analysis-of-european-breast-cancer-cohorts
#16
Chris R Cardwell, Anton Pottegård, Evelien Vaes, Hans Garmo, Liam J Murray, Chris Brown, Pauline A J Vissers, Michael O'Rorke, Kala Visvanathan, Deirdre Cronin-Fenton, Harlinde De Schutter, Mats Lambe, Des G Powe, Myrthe P P van Herk-Sukel, Anna Gavin, Søren Friis, Linda Sharp, Kathleen Bennett
BACKGROUND: Preclinical studies have demonstrated that propranolol inhibits several pathways involved in breast cancer progression and metastasis. We investigated whether breast cancer patients who used propranolol, or other non-selective beta-blockers, had reduced breast cancer-specific or all-cause mortality in eight European cohorts. METHODS: Incident breast cancer patients were identified from eight cancer registries and compiled through the European Cancer Pharmacoepidemiology Network...
December 1, 2016: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/27899953/repurposing-drugs-in-oncology-redo-propranolol-as-an-anti-cancer-agent
#17
Pan Pantziarka, Gauthier Bouche, Vidula Sukhatme, Lydie Meheus, Ilse Rooman, Vikas P Sukhatme
Propranolol (PRO) is a well-known and widely used non-selective beta-adrenergic receptor antagonist (beta-blocker), with a range of actions which are of interest in an oncological context. PRO displays effects on cellular proliferation and invasion, on the immune system, on the angiogenic cascade, and on tumour cell sensitivity to existing treatments. Both pre-clinical and clinical evidence of these effects, in multiple cancer types, is assessed and summarised and relevant mechanisms of action outlined. In particular there is evidence that PRO is effective at multiple points in the metastatic cascade, particularly in the context of the post-surgical wound response...
2016: Ecancermedicalscience
https://www.readbyqxmd.com/read/27890326/the-effect-of-metabolic-comorbidities-and-commonly-used-drugs-on-the-prognosis-of-patients-with-ovarian-cancer
#18
Daniel Bar, Ofer Lavie, Nili Stein, Ido Feferkorn, Ayelet Shai
BACKGROUND: Diabetes mellitus is associated with an increased risk of recurrence in patients with ovarian cancer. Retrospective studies suggested that the use of statins, metformin and beta blockers is associated with improved prognosis in these patients. Patients with diabetes often suffer from hypertension and are usually treated concomitantly by several classes of drugs. Our aim was to assess the independent contribution of diabetes mellitus and hypertension and of the use of aspirin, statins, metformin and beta blockers on the risk of ovarian cancer recurrence and mortality...
December 2016: European Journal of Obstetrics, Gynecology, and Reproductive Biology
https://www.readbyqxmd.com/read/27863705/intake-of-selective-beta-blockers-has-no-impact-on-survival-in-patients-with-epithelial-ovarian-cancer
#19
Florian Heitz, Alexandra Hengsbach, Philipp Harter, Alexander Traut, Beyhan Ataseven, Stephanie Schneider, Sonia Prader, Christian Kurzeder, Mareike Sporkmann, Andreas du Bois
BACKGROUND AND OBJECTIVE: Some authors have claimed a significant impact of β-blocking agents on outcome in epithelial ovarian cancer (EOC). This study investigated the impact of concurrent medication with selective beta blockers (SBB) in patients undergoing primary treatment for EOC. METHODS: The study included all consecutive patients with primary EOC treated in two tertiary gynecological-oncologic units between 1999 and 2014. Medication was retrospectively analyzed by chart review...
January 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/27830273/-summary-of-the-esc-position-paper-on-cancer-treatment-and-cardiovascular-toxicity
#20
J Hoog, S Achenbach
The numbers of survivors of cancer have increased as a consequence of advances in chemotherapy; however, the side effects of cancer treatment have become increasingly more important. The most frequent side effects include cardiovascular complications, which can lead to acute and delayed morbidity and mortality, often many years later. The discipline of cardio-oncology deals with the prevention, diagnostics and treatment of cardiovascular diseases caused by cancer therapy. The most important cardiovascular side effects of cytostatic therapy are heart failure due to myocardial dysfunction (cardiotoxicity), coronary artery disease, valvular disease and ventricular arrhythmia as a result of QT extension...
December 2016: Herz
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