Therapeutic Efficacy of Oncolytic Viruses in Fighting Cancer: Recent Advances and Perspective.

Immunotherapy is at the cutting edge of modern cancer treatment. Innovative medicines have been developed with varying degrees of success that target all aspects of tumor biology: tumors, niches, and the immune system. Oncolytic viruses (OVs) are a novel and potentially immunotherapeutic approach for cancer treatment. OVs reproduce exclusively in cancer cells, causing the tumor mass to lyse. OVs can also activate the immune system in addition to their primary activity. Tumors create an immunosuppressive environment by suppressing the immune system's ability to respond to tumor cells. By injecting OVs into the tumor, the immune system is stimulated, allowing it to generate a robust and long-lasting response against the tumor. The essential biological properties of oncolytic viruses, as well as the underlying mechanisms that enable their usage as prospective anticancer medicines, are outlined in this review. We also discuss the increased efficacy of virotherapy when combined with other cancer medications.

Dendritic cells and natural killer cells: The road to a successful oncolytic virotherapy.

Every type of cancer tissue is theoretically more vulnerable to viral infection. This natural proclivity has been harnessed as a new anti-cancer therapy by employing oncolytic viruses (OVs) to selectively infect and destroy cancer cells while providing little or no harm with no toxicity to the host. Whereas the primary oncolytic capabilities of OVs initially sparked the greatest concern, the predominant focus of research is on the association between OVs and the host immune system. Numerous OVs are potent causal agents of class I MHC pathway-related chemicals, enabling early tumor/viral immune recognition and cytokine-mediated response. The modified OVs have been studied for their ability to bind to dendritic cells (DCs) by expressing growth factors, chemokines, cytokines, and defensins inside the viral genome. OVs, like reovirus, can directly infect DCs, causing them to release chemokines and cytokines that attract and excite natural killer (NK) cells. In addition, OVs can directly alter cancer cells' sensitivity to NK by altering the expression levels of NK cell activators and inhibitors on cancerous cells. Therefore, NK cells and DCs in modulating the therapeutic response should be considered when developing and improving future OV-based therapeutics, whether modified to express transgenes or used in combination with other drugs/immunotherapies. Concerning the close relationship between NK cells and DCs in the potential of OVs to kill tumor cells, we explore how DCs and NK cells in tumor microenvironment affect oncolytic virotherapy and summarize additional information about the interaction mentioned above in detail in this work.

Association of platelet collagen receptor polymorphisms with premature acute myocardial infarction.

The impact of platelet collagen receptor polymorphisms in the pathogenesis of myocardial infarction at young age remains unknown. To determine whether either of the two platelet collagen receptor polymorphisms (GP VI T13254C and GP Ia C807T) was associated with premature acute myocardial infarction. One hundred patients with premature acute myocardial infarction and 100 age-matched controls with normal coronary angiograms were studied. Genotyping was done using PCR followed by restriction fragment length polymorphism (RFLP). GP Ia C807T polymorphism was more frequent in the patient group (65%) than in the control group (53%). However, there was no association between this polymorphism and premature acute myocardial infarction (P = 0.08). The prevalence of T13254C polymorphism did not differ between patients (38%) and controls (33%), and this polymorphism was not associated with premature acute myocardial infarction (P = 0.46). Logistic regression analysis also indicated no association between these polymorphisms and premature acute myocardial infarction (C807T with P = 0.51 and T13254C with P = 0.20). There is no association between GP VI T13254C or GP Ia C807T polymorphisms and premature acute myocardial infarction.

Prediction of response to cardiac resynchronization therapy using simple electrocardiographic and echocardiographic tools.

AIMS: To predict response to cardiac resynchronization therapy (CRT) in patients with heart failure (HF) and intraventricular conduction delay. METHODS AND RESULTS: The study population consisted of 82 consecutive HF patients with standard CRT indications. Patients were classified as responders, if they were alive without cardiac decompensation and experienced >or=15% decrease in left ventricular end-systolic volume. Sixty-eight percent of the enrolled patients responded to CRT. When compared with non-responders, responders had a wider baseline QRS width (P = 0.001), more marked QRS shortening (DeltaQRS) immediately after CRT (P = 0.001), and a better improvement in aortic velocity time integral (VTI) 24 h after CRT (P = 0.02). Moreover, there was a trend towards a greater baseline intraventricular dyssynchrony in the responder group (P = 0.07). By multivariable logistic regression, the baseline QRS width (OR: 0.95, 95% CI: 0.90-0.97, P = 0.001), DeltaQRS (OR: 1.038, 95% CI: 1.012-1.064, P = 0.003), and acute aortic VTI (OR: 0.81, 95% CI: 0.68-0.96, P = 0.017) emerged as independent predictors of response to CRT. Receiver operating characteristic curve analysis identified a QRS width >145 ms, DeltaQRS >20 ms, and aortic VTI >14 cm to predict responders. CONCLUSION: A positive response to CRT was observed in 68% of the patients. Cardiac resynchronization therapy response is predictable using simple electrocardiographic and echocardiographic data.

Pharmacological prevention of the deleterious effects of cardiopulmonary bypass.

Indomethacin is a known immune modulator that inhibits cyclooxygenase. Studies indicate that ketoconazole, a selective lipoxygenase and thromboxane A(2) synthetase inhibitor, can prevent activation of the inflammatory cascade by inhibition of proinflammatory mediators. This study was designed to determine if ketoconazole or indomethacin could reduce the adverse effects of extracorporeal circulation. As a double-blind prospective study, 76 patients were randomized into 3 groups according to preoperative medication: indomethacin, ketoconazole, and placebo groups, with 25, 26, and 25 patients, respectively. Four types of parameters were evaluated preoperatively and up to 24 hr after cardiac surgery in all patients: inflammatory (complement C3 and C4, C-reactive protein, immunoglobulins); hematologic; coagulation; and physiologic (blood loss, fluid and blood components received, weight gain, and duration of ventilation). Statistical analyses showed similar patient profiles in each group. Complement C4 decreased in all groups postoperatively, but significantly less in the indomethacin group ( p < 0.01). Ketoconazole reduced postoperative bleeding ( p < 0.0001) as well as the incidence of re-operation for bleeding ( p = 0.05). It was concluded that indomethacin decreases complement (specifically C4) consumption during cardiopulmonary bypass, and ketoconazole may reduce postoperative bleeding by limiting coagulation abnormalities in cardiac surgery patients.

Evaluation of post-radiofrequency myocardial injury by measuring cardiac troponin I levels.

BACKGROUND: The aim of this study was to investigate the extent of myocardial injury created by radiofrequency (RF) ablation. We assessed the changes in levels of cardiac biochemical markers in patients who underwent RF ablation and we sought to evaluate the utility of cardiac troponin I (cTnI) in detecting minor myocardial injury following RF ablation and determine its procedural correlates. METHODS: We analyzed the data of 115 consecutive patients who underwent RF ablation. The target sites of RF ablation were slow pathway in 56, left atrioventricular (AV) annulus in 31, right AV annulus in 14, atrial wall in 3, ventricular wall in 6 and AV node in 3 patients. The levels of creatine kinase (CK), CK-MB, cTnI and myoglobin were compared with procedural data and targeted arrhythmia. RESULTS: Post-RF ablation the concentration of cTnI, CM-MB, CK and myoglobin were significantly different than those of the initial sample. The mean and peak cTnI levels were raised above normal in 63 patients (54.8%). Mean levels of cTnI correlated with the site of RF ablation, being significant for slow pathway ablation, ventricular tachycardia and left AV annulus. We also found a significant association of mean CK-MB, CK levels and left AV annulus. CONCLUSION: Our results indicate that radiofrequency ablation results in only minor injury. This marker is effective for detection of RF current induced myocardial injury. Lesions applied to the mitral annulus at the ventricular endocardium are associated with significantly greater myocardial damage.