Publications by authors named "R Yarchoan"
The clinical management of people with multidrug-resistant (MDR) human immunodeficiency virus (HIV) remains challenging despite continued development of antiretroviral agents. A 58-year-old male individual with MDR HIV and Kaposi sarcoma (KS) was treated with a new antiretroviral regimen consisting of anti-CD4 domain 1 antibody UB-421 and capsid inhibitor lenacapavir. The individual experienced delayed but sustained suppression of plasma viremia and a substantial increase in the CD4 T cell count.
View Article and Find Full Text PDFIn this editorial, we highlight the potential use of inhibitors of hypoxia-inducible factors (HIFs) for the use in Kaposi's sarcoma associated herpesvirus (KSHV) (also known as human herpesvirus-8) related malignancies. The past 20 years has accumulated detailed knowledge of the role of these factors in ensuring the maintenance of the KSHV in infected cells, in aiding the growth of the virus infected cells and aiding in the spread of virus from infected cells by inducing lytic reactivation. Today, a wide range of inhibitors for HIFs are currently being clinically evaluated for use in treating a variety of cancers.
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- Kaposi sarcoma (KS) is a cancer linked to abnormal blood vessel growth, primarily caused by the Kaposi sarcoma herpesvirus (KSHV) found in specialized tumor cells.
- Researchers have developed a method to grow patient-derived KS tumors in mice, allowing them to maintain the KSHV infection and tumor characteristics for extended periods, which is crucial for studying the disease.
- The study found that the resulting tumors displayed increased density of KSHV-infected cells, higher proliferation rates, and maintained gene expressions associated with KS, indicating that these mouse models can help in understanding the disease and testing new treatments.
Coronaviruses rely on the viral-encoded chymotrypsin-like main protease (M or 3CL) for replication and assembly. Our previous research on M of SARS-CoV-2 identified cysteine 300 (Cys300) as a potential allosteric site of M inhibition. Here, we identified tixocortol (TX) as a covalent modifier of Cys300 which inhibits M activity as well as in a cell-based M expression assay.
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- The Cancer Immunotherapy Trials Network 12 study showed that pembrolizumab is safe and effective for treating advanced Kaposi sarcoma (KS) in people with HIV on antiretroviral therapy.
- In a phase I trial involving 32 participants, 62.1% had a positive response to pembrolizumab, with even higher rates (87.5%) for those who hadn't received previous KS treatments.
- The treatment led to significant progression-free survival, with a median of 28.2 months, and immune-mediated adverse events were effectively managed according to established guidelines.