Dolutegravir Inhibits Proliferation and Motility of BT-20 Tumor Cells Through Inhibition of Human Endogenous Retrovirus Type K.

Increasing evidence points to the role of endogenous retroviruses (ERVs) in driving cancer cell proliferation. The purpose of this study was to explore the possibility of repurposing antiretroviral agents to inhibit ERVs as a new approach to cancer treatment. We found that an integrase strand-transfer inhibitor, dolutegravir (DTG), effectively inhibited the proliferation of multiple cancer cell lines and its antiproliferative potency was positively correlated with the expression levels of the human endogenous retrovirus type K (HERV-K). DTG inhibited the expression of HERV-K in multiple human cancer cell lines and the mouse mammary tumor virus (MMTV) in the murine 4T1 mammary cancer cell line. We chose the fast-growing BT-20 cell line as a model to study the in vitro antiproliferative mechanisms of DTG. BT-20 cells overexpressing both HERV-K env and pol genes became more resistant to DTG than cells transduced with vector alone. Knockdown of HERV-K also increased DTG resistance of BT-20 cells. The antiproliferative effect of DTG correlated with enhanced expression of E-cadherin and reduction in cell motility and invasiveness. Surprisingly, DTG stimulated expression of the env gene of MMTV in vivo and promoted metastasis of 4T1 tumor cells to the lungs. Taken together, our data support the role of ERVs in tumor development and encourage the further search for antiretroviral agents to treat malignancies in which ERVs are active.

Application of Intralesion Ultrasound-Guided Laser Ablation for Plantar Foot Mass Involving Arteriovenous Fistula: A Case Report.

Penetrating and blunt trauma to the plantar aspect of the foot are common. Both penetrating and blunt trauma may be associated with an injury to the blood vessels, which may go undetected clinically. A minor puncture, blunt trauma and repeated blunt trauma can injure small arteries leading to an arteriovenous fistula (AVF). The arterial rupture leads to a system of veins creating a small AVF and appearing clinically as a blue colored, painful lesion. A case of such an injury is presented where the clinical examination, magnetic resonance arteriogram and point of service ultrasound with duplex imaging was used to diagnose the AVF. The AVF was treated in the clinic with a percutaneous ultrasound-guided laser procedure. The laser procedure was effective and there was minimal post procedural morbidity.