Longitudinal Changes in Multiple Biomarkers Are Associated with Cardiotoxicity in Breast Cancer Patients Treated with Doxorubicin, Taxanes, and Trastuzumab.

Background: Biomarkers may play an important role in identifying patients at risk for cancer therapy cardiotoxicity. Our objectives were to define the patterns of change in biomarkers with cancer therapy and their associations with cardiotoxicity.

Methods: In a multicenter cohort of 78 breast cancer patients undergoing doxorubicin and trastuzumab therapy, 8 biomarkers were evaluated at baseline and every 3 months over a maximum follow-up of 15 months.

Time Trends of Left Ventricular Ejection Fraction and Myocardial Deformation Indices in a Cohort of Women with Breast Cancer Treated with Anthracyclines, Taxanes, and Trastuzumab.

Background: Trastuzumab, a HER2 monoclonal antibody, has transformed the prognosis of patients with the aggressive HER2-positive breast cancer type. Trastuzumab augments the cardiotoxic effects of anthracyclines, but its effect is thought to be at least partially reversible. The objective of this study was to examine the time trends of left ventricular (LV) size and function in a cohort of women treated with anthracyclines and trastuzumab.

Early increases in multiple biomarkers predict subsequent cardiotoxicity in patients with breast cancer treated with doxorubicin, taxanes, and trastuzumab.

Objectives: The aim of this study was to determine if individual or multiple biomarkers are associated with cardiotoxicity in patients with breast cancer undergoing cancer therapy.

Background: Current methods to identify patients at risk for cardiotoxicity from cancer therapy are inadequate.

Methods: We measured 8 biomarkers in a multicenter cohort of 78 patients with breast cancer undergoing doxorubicin and trastuzumab therapy: ultrasensitive troponin I (TnI), high-sensitivity C-reactive protein (CRP), N-terminal pro-B-type natriuretic peptide (NT-proBNP), growth differentiation factor (GDF)-15, myeloperoxidase (MPO), placental growth factor (PlGF), soluble fms-like tyrosine kinase receptor (sFlt)-1, and galectin (gal)-3.

Human resistin in chemotherapy-induced heart failure in humanized male mice and in women treated for breast cancer.

Resistin is a circulating mediator of insulin resistance mainly expressed in human monocytes and responsive to inflammatory stimuli. Recent clinical studies have connected elevated resistin levels with the development and severity of heart failure. To further our understanding of the role of human resistin in heart failure, we studied a humanized mouse model lacking murine resistin but transgenic for the human Retn gene (Hum-Retn mice), which exhibits basal and inflammation-stimulated resistin levels similar to humans.

Effects of subacute dietary salt intake and acute volume expansion on diastolic function in young normotensive individuals.

Aims: Chronic excess salt intake may have blood pressure-independent adverse effects on the heart such as myocardial hypertrophy and fibrosis. Effects of subacute sodium loading with excess dietary salt on diastolic function in normotensive individuals have been conflicting and the mechanisms are poorly understood.

Methods And Results: Thirteen healthy normotensive subjects (age 24 ± 4 years) entered a 2-week crossover study with 1 week of a low-salt diet <10 mEq/day and 1 week of a high-salt diet >200 mEq/day.

Assessment of echocardiography and biomarkers for the extended prediction of cardiotoxicity in patients treated with anthracyclines, taxanes, and trastuzumab.

Background: Because cancer patients survive longer, the impact of cardiotoxicity associated with the use of cancer treatments escalates. The present study investigates whether early alterations of myocardial strain and blood biomarkers predict incident cardiotoxicity in patients with breast cancer during treatment with anthracyclines, taxanes, and trastuzumab.

Methods And Results: Eighty-one women with newly diagnosed human epidermal growth factor receptor 2-positive breast cancer, treated with anthracyclines followed by taxanes and trastuzumab were enrolled to be evaluated every 3 months during their cancer therapy (total of 15 months) using echocardiograms and blood samples.

Newest echocardiographic techniques for the detection of cardiotoxicity and heart failure during chemotherapy.

Chemotherapy-induced cardiotoxicity has become a significant public health issue. Left ventricular ejection fraction is routinely used to monitor cardiotoxicity but fails to detect subtle alterations in cardiac function. Improvements in the measurement of left ventricular ejection fraction, physical or pharmacologic stressors, and novel cardiac functional indices may be useful in the detection of cardiotoxicity.

Early detection and prediction of cardiotoxicity in chemotherapy-treated patients.

As breast cancer survival increases, cardiotoxicity associated with chemotherapeutic regimens such as anthracyclines and trastuzumab becomes a more significant issue. Assessment of the left ventricular (LV) ejection fraction fails to detect subtle alterations in LV function. The objective of this study was to evaluate whether more sensitive echocardiographic measurements and biomarkers could predict future cardiac dysfunction in chemotherapy-treated patients.

Altered adhesion molecules expression on peripheral blood mononuclear cells from patients with systemic sclerosis and clinical correlations.

The aim of the study was to evaluate the expressions of adhesion molecules (AM) on peripheral blood mononuclear cells (PBMNC) from systemic sclerosis (SSc) patients. Thirty-one SSc patients (ACR) and 20 normal subjects were selected for the study. PBMNC were analyzed for LFA-1alpha, LFA-1beta, ICAM-3, ICAM-1, and L: -selectin expressions.

Inflammatory arthritis can be reined in by CpG-induced DC-NK cell cross talk.

Unmethylated CpG-oligodeoxynucleotides (ODNs) are generally thought of as potent adjuvants with considerable therapeutic potential to enhance immune responses against microbes and tumors. Surprisingly, certain so-called stimulatory CpG-ODNs strongly inhibited the effector phase of inflammatory arthritis in the K/BxN serum transfer system, either preventively or therapeutically. Also unexpected was that the inhibitory influence did not depend on the adaptive immune system cells mobilized in an immunostimulatory context.

Colonic adenocarcinomas: near-infrared microcatheter imaging of smart probes for early detection--study in mice.

Purpose: To prospectively evaluate the ability of micro-fiberoptic catheters, which simultaneously record white light and near-infrared (NIR) images, to reveal colonic neoplasms after the intravenous administration of activatable "smart" probes that increase in NIR fluorescence subsequent to protease activation.

Materials And Methods: The institutional animal care committee approved all animal experiments. CT26 tumor cells were orthotopically implanted into the descending colon of C57BL6/J mice (n=10).

Dialysis-associated systemic fibrosis (nephrogenic fibrosing dermopathy): study of inflammatory cells and transforming growth factor beta1 expression in affected skin.

Objective: Nephrogenic fibrosing dermopathy (NFD) is a newly recognized cutaneous fibrotic disorder occurring in individuals with end-stage renal disease (ESRD). The aim of the present study was to describe the clinical and histopathologic features of 9 new cases and to characterize the inflammatory cells and expression of transforming growth factor beta1 (TGFbeta1) in affected skin.

Methods: Clinical and laboratory assessments, including serology and pulmonary function studies, were performed in 9 patients undergoing long-term dialysis (8 hemodialysis; 1 peritoneal dialysis) for ESRD of diverse etiologies.