Myocardial perfusion imaging with contrast echocardiography

Advances in myocardial perfusion imaging have firmly established the use of noninvasive techniques capable of providing useful information over a broad range of diagnostic and therapeutic cardiovascular problems. Evaluating regional myocardial perfusion abnormalities is a cornerstone for the diagnosis of coronary artery disease, risk assessment in those with known disease, and determination of myocardial viability. The clinical use of myocardial perfusion imaging and the current limitations of existing techniques continue to promote the development of new technologies capable of assessing microvascular and capillary perfusion abnormalities on a global myocardial level. Myocardial contrast echocardiography is an emerging technique capable of rapidly assessing myocardial perfusion at the capillary level in many different clinical settings. This article focuses on myocardial contrast-enhanced ultrasound perfusion techniques, emphasizing the unique information this modality provides compared with other noninvasive perfusion imaging techniques.     

Acute myeloid leukemia in the elderly: conventional and novel treatment approaches

Acute Myeloid Leukemia (AML) is a disorder affecting primarily elderly individuals and poses significant treatment challenges. Much has been learned about the underlying immunologic, cytogenetic and molecular features of AML in recent years, and many features have been identified that portend a poor prognosis for elderly patients with newly diagnosed AML. Despite this, treatment outcomes for elderly patients remain poor for both newly diagnosed and relapsed disease. While conventional treatment approaches may be appropriate for some elderly patients, the vast majority do not tolerate intensive chemotherapy well, thus alternative strategies have been investigated. Here we review both conventional and novel treatment approaches for elderly patients with AML, including agents in early clinical trials. Treatment options have been divided into several discussions, including conventional treatments, agents complementary to conventional treatments, alternatives to conventional induction therapies, post-induction treatment, and relapsed disease. Current and developing research focuses upon identifying subgroups of patients that benefit more from specific chemotherapeutic agents. Treating elderly patients with AML requires an organized, multidisciplinary approach, taking into account individual patient characteristics, preferences, and comorbidities when formulating treatment plans.     

Dysregulation of the epigenome in triple-negative breast cancers: Basal-like and claudin-low breast cancers express aberrant DNA hypermethylation

A subset of human breast cancer cell lines exhibits aberrant DNA hypermethylation that is characterized by hyperactivity of the DNA methyltransferase enzymes, overexpression of DNMT3b, and concurrent methylation-dependent silencing of numerous epigenetic biomarker genes. The objective of this study was to determine if this aberrant DNA hypermethylation (i) is found in primary breast cancers, (ii) is associated with specific breast cancer molecular subtypes, and (iii) influences patient outcomes. Analysis of epigenetic biomarker genes (CDH1, CEACAM6, CST6, ESR1, GNA11, MUC1, MYB, SCNN1A, and TFF3) identified a gene expression signature characterized by reduced expression levels or loss of expression among a cohort of primary breast cancers. The breast cancers that express this gene expression signature are enriched for triple-negative subtypes — basal-like and claudin-low breast cancers. Methylation analysis of primary breast cancers showed extensive promoter hypermethylation of epigenetic biomarker genes among triple-negative breast cancers, compared to other breast cancer subclasses where promoter hypermethylation events were less frequent. Furthermore, triple-negative breast cancers either did not express or expressed significantly reduced levels of protein corresponding to methylation-sensitive biomarker gene products. Together, these findings suggest strongly that loss of epigenetic biomarker gene expression is frequently associated with gene promoter hypermethylation events. We propose that aberrant DNA hypermethylation is a common characteristic of triple-negative breast cancers and may represent a fundamental biological property of basal-like and claudin-low breast cancers. Kaplan–Meier analysis of relapse-free survival revealed a survival disadvantage for patients with breast cancers that exhibit aberrant DNA hypermethylation. Identification of this distinguishing trait among triple-negative breast cancers forms the basis for development of new rational therapies that target the epigenome in patients with basal-like and claudin-low breast cancers.