Cardiotoxicity of Biological Therapies in Cancer Patients: An In-depth Review.

Cardiotoxicity from chemotherapy regimens has been long reported. However, the understanding of cardiac side effects of biological therapies is rapidly evolving. With cancer patients achieving higher life expectancy due to the use of personalized medicine and novel targeted anticancer agents, the occurrence of cardiotoxicity is becoming more significant. Novel biological therapies include anti-HER2 antibodies, tyrosine kinase inhibitors, bruton kinase inhibitors, antivascular endothelial growth factors, proteasome inhibitors, immunomodulator drugs, and immune checkpoint inhibitors. Potential cardiovascular toxicities linked to these anticancer agents include hypertension, arrhythmias, QT prolongation, myocardial ischemia and infarction, left ventricular dysfunction, congestive heart failure, and thromboembolism. Cardiac biomarkers, electrocardiography, echocardiography and magnetic resonance imaging are common diagnostic modalities used for early detection of these complications and timely intervention. This review discusses the various types of cardiotoxicities caused by novel anticancer biologic agents, their molecular and pathophysiological mechanisms, risk factors, and diagnostic and management strategies that can be used to prevent, minimize, and treat them.

Effect of low fluence diode laser irradiation on the hydraulic conductivity of perfused trabecular meshwork endothelial cell monolayers.

OBJECTIVE: To determine the effect of low-fluence diode laser irradiation upon the fluid perfusion characteristics of cultured human trabecular meshwork cell monolayers when placed in a specially designed testing apparatus and subjected to fluid flow driven by a hydrostatic pressure gradient. METHODS: Two experimental series were conducted. In the first series, six low-fluence diode laser irradiation experiments were conducted using cultured human trabecular meshwork cell monolayers grown on filter supports. Upon reaching a steady state perfusion condition at approximately 5.0 mmHg, monolayers were irradiated at fluencies ranging from 0.2619 to 0.8571 J/cm2 using a diode laser (lambda=810 nm). Perfusion and data collection continued for 45 minutes post-irradiation, after which the monolayers were tested to determine post-experimental viability. Hydraulic conductivity values were analyzed for post-irradiation response in 2.5-minute intervals, grouped by viability. In the second series, a total of six irradiated experiments and six simultaneous nonirradiated control experiments were conducted. Fluence values of 0.3571 J/cm2 (n=3) and 0.4286 J/cm2 (n=3) were used. Hydraulic conductivity values were analyzed for post-irradiation response in 2.5-minute intervals, grouped by irradiated vs. nonirradiated control groups. RESULTS: In the first series, analysis showed that the viable monolayers exhibited a statistically significant increase in hydraulic conductivity (p<0.001) from 10 minutes post-irradiation onward. The non-viable monolayers exhibited a statistically significant decrease in hydraulic conductivity. In the second series, irradiated groups showed a significant difference (p<0.001) from nonirradiated controls from 10 minutes post-irradiation onward. CONCLUSION: Low-fluence diode laser irradiation increases hydraulic conductivity in viable perfused TM cell monolayers when compared to baseline values or simultaneous nonirradiated controls while decreasing hydraulic conductivity in nonviable monolayers.