Cardiac complications in cancer treatment - A review.

Cardiac dysfunction is often associated with effective cancer treatment. A number of targeted therapies against cancer have been observed to cause cardiac dysfunction. In some instances, a patient may outlive his or her cancer but die due to heart failure. Recent research has been focused on the development of new avenues and technological advancements to monitor clinical cardiotoxicity and cardiac dysfunction due to anticancer treatment. These newer treatment options are also increasingly effective and are focused more on post-cancer life. The present review article expands the current view of cardiac complications involved in cancer treatment along with the recent developments in the area.

The importance of clinical grading of heart failure and other cardiac toxicities during chemotherapy: updating the common terminology criteria for clinical trial reporting.

Although the use of chemotherapy and targeted therapy has improved the clinical benefit, progression-free survival, and overall survival of various cancers in recent years, old and new toxicities have limited their use. To balance the risk with the benefit of treatment, Common Toxicity Criteria and now Common Terminology Criteria for Adverse Events (CTCAE) have been used by the oncology community for more than 20 years to assess toxicity from cancer treatment. This article details the description and grading of cardiac toxicities reported in association with cancer treatment and the use of CTCAE to assess them.

Cardiotoxicity of molecularly targeted agents.

Cardiac toxicity of molecularly targeted cancer agents is increasingly recognized as a significant side effect of chemotherapy. These new potent therapies may not only affect the survival of cancer cells, but have the potential to adversely impact normal cardiac and vascular function. Unraveling the mechanisms by which these therapies affect the heart and vasculature is crucial for improving drug design and finding alternative therapies to protect patients predisposed to cardiovascular disease. In this review, we summarize the classification and side effects of currently approved molecularly targeted chemotherapeutics.

Isolation, purification, crystallization and preliminary crystallographic studies of sagitoxin, an oligomeric cardiotoxin from the venom of Naja naja saggitifera.

Sagitoxin, a novel cardiotoxin from the venom of Naja naja saggitifera, has been successfully isolated, purified to homogeneity and crystallized. The toxin was purified using successive separation steps on a CM-Sephadex C-50 column and a reverse-phase column. The 6.75 kDa toxin was sequenced by the Edman method using a PPSQ-21 protein sequencer. It was crystallized using the hanging-drop vapour-diffusion method. The hexagonal-shaped crystals diffracted to 3.0 A resolution and belonged to space group P6(4), with unit-cell parameters a = b = 111.1, c = 137.3 A, gamma = 120 degrees . There are 36 molecules in the unit cell, which has an approximate solvent content of 80%. Structure determination revealed that the molecules of sagitoxin associate in a hexameric form and create a pore in the centre which has functional significance.

Cardiotoxic effects of antihistamines: from basics to clinics (...and back).

Drug-induced arrhythmias, particularly those caused by a prolonged QT interval, have become a critical safety issue for compound selection during development by pharmaceutical companies and for health care regulators. The last two decades have witnessed enormous progress in the definition of the clinical conditions that facilitate the occurrence of such serious adverse effects, of its molecular basis, and in the preclinical strategies aimed at early identification of the cardiotoxic liability of compounds undergoing investigation or already used in the clinic. Moreover, despite the fact that acquired factors play an obvious role in drug-induced arrhythmias, it has become evident that the disease is often manifested upon the interaction of strong environmental stressors with specific genetic determinants of the affected individuals; in that sense, few examples can illustrate the existing interaction between acquired and genetic factors in disease manifestation better than drug-induced arrhythmogenesis. Progress in this field has been mainly driven by a strong interaction among various disciplines, including medicinal chemistry, pharmacology, electrophysiology, molecular genetics, and clinical cardiology; such an interdisciplinary approach has often generated unexpected discoveries of great clinical value, allowing clinicians to drive drug selection toward compounds of proven efficacy and safety. Historically, studies on antihistamines have paved the way for much of our current understanding of the mechanisms and problems associated with QT prolongation and drug-induced arrhythmogenesis; therefore, in this perspective, we will attempt to summarize how basic research studies have helped the interpretation of clinically relevant phenomena (from basics to clinics...) and how this information has prompted new emphasis in preclinical studies aimed at predicting the cardiotoxic potential of compounds (...and back). The current availability of several strategies provided with great predictive potential, together with an increased awareness of physicians, pharmaceutical industries, and health care regulators to this potentially serious cardiovascular side effect, has significantly decreased the risk associated with drug-induced arrhythmias caused by drugs newly introduced into the market; nevertheless, given the large number of cases of QT prolongation still occurring during treatment with a wide variety of congeners, it seems appropriate to review the issue of the cardiotoxic actions of antihistamines, as a better comprehension of the underlying mechanisms and risk factors is likely to contribute to the improvement of the risk/benefit ratio for pharmacological treatment in several therapeutic areas.