The recent Food and Drug Administration approval of immunogenic oncolytic virus (OV) has opened a new era in the treatment of advanced melanoma; however, approximately 50% of patients with melanoma develop brain metastasis, and currently there are no beneficial treatment options for such patients. To model the progression of metastases seen in patients and to overcome the hurdles of systemic delivery of OV, we developed melanoma brain metastasis models in immunocompromised and immunocompetent mice, and tested the fate and efficacy of oncolytic herpes simplex virus (oHSV)-armed mesenchymal stem cells (MSCs). Using brain-seeking patient-derived melanoma cells and real-time in vivo imaging, we show a widespread distribution of micrometastases and macrometastases in the brain, recapitulating the progression of multifoci metastases seen in patients. We armed MSCs with different oHSV variants (MSC-oHSV) and found that intracarotid administration of MSC-oHSV, but not of purified oHSV alone, effectively tracks metastatic tumor lesions and significantly prolongs the survival of brain tumor-bearing mice. In a syngeneic model of melanoma brain metastasis, a combination of MSC-oHSV and PD-L1 blockade increases IFNγ-producing CD8 + tumor-infiltrating T lymphocytes and results in a profound extension of the median survival of treated animals. This study thus demonstrates the utility of MSCs as OV carriers to disseminated brain lesions, and provides a clinically applicable therapeutic platform to target melanoma brain metastasis.stem cells | oncolytic virus | tumors | metastasis | imaging M elanoma, the most aggressive type of skin cancer, accounts for a large proportion of skin cancer-related deaths (1). Among all cancer types, melanoma has a particularly high propensity to metastasize to the brain, occurring in >50% of all patients with advanced disease. More than 90% of melanoma brain metastases lead to death, and the median survival is 17-22 wk after detection (2-4).Current therapeutic options of chemotherapy, surgery, and radiation have very limited efficacy for patients with melanoma brain metastasis (5-7). These patients either have multiple metastatic lesions or diagnostically challenging asymptomatic lesions, making surgery an inadequate therapeutic option by itself. In addition, the blood-brain barrier (BBB) limits central nervous system (CNS) penetration of systemic therapies, and the negative side effects of radiotherapy (8) pose challenges for the success of existing therapies, contributing to the failure to improve overall patient survival. As such, there is an urgent need for new therapies for melanoma brain metastasis.The development and characterization of preclinical tumor models that authentically recapitulate the clinical disease settings are critical for developing and testing new therapies. Most previous studies have used either subcutaneous (s.c.) injection or intracranial injection of established melanoma lines in mice (9-11), which do not mimic the actual clinical settings of melanoma brain metastasis,...
A s Information Technology has developed, there has been a birth of new medical fields including telemedicine, e-Health, and u-Health. The differences between the new terms resulted from renewed definitions with the development of technology. However, aside from the simple change in terminology medical services that use the terms has expanded along with the change in terminology. Currently most countries use telemedicine as a part of their healthcare system. As such, related devices and services have been slated to become a totally new industry. In Korea, due to the advances in IT, Increase in medically vulnerable and aging population, and increase in the number of patients with chronic disease, telemedicine has been widely used in public healthcare system. Several developmental attempts by public and private sectors have had limited success due to legal and institutional limitations but recent changes in medical law and movement to allow tele-diagnosis and treatment in the public sector has brought in a new era. Although development of telemedicine technology may be the key, it is even more important that the development in medical services models as well as their application be on the same track. Furthermore, from the clinical and academic standpoint, the aspects of safety, efficiency, and economic viability must be thoroughly tested and applied. Most importantly, active involvement from the medical community in development of new medical technology as well as new service models for diagnosis and treatment is required. The most advanced technology would be useless if it is not being actively utilized by the medical community in the treatment and management of patients.
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