Kaposi Sarcoma

Overall survival is increased by prophylactic ganciclovir. Thus, whole-virus KSHV-transgenic mice represent an accurate model for KS and open the door for the genetic dissection of KS pathogenesis and evaluation of therapies, including vaccines.

P=N/A, N=150, Not yet recruiting, National Cancer Institute (NCI)

Finally, we report that JH295 treatment sensitized lymphomas to other chemotherapeutic agents such as rapamycin, resulting in enhanced cancer cell death...NEK2 inhibition resulted in PEL apoptosis and reduced tumor burden in a mouse model. NEK2 inhibition also reduced drug resistance.

KSHV viral load in BAL shows potential for aiding in pKS diagnosis. Patients with pKS also have evidence of cytokine dysregulation in BAL.

The co-loaded dual-drug nanocomplex not only inhibits the proliferation and migration of KSHV-positive cells but also decreases the mRNA expression level of KSHV lytic and latent genes. In conclusion, this co-loaded dual-drug nanocomplex may provide an attractive strategy for antiviral drug delivery and anti-KSHV therapy.

Consequently, a SIRT3-specific inhibitor, 3-TYP, suppresses KSHV-induced cellular transformation by inducing ferroptosis. Our findings unveil novel roles of vIL-6 and SERBP1 deacetylation in regulating ferroptosis and KSHV-induced cellular transformation, and establish the vIL-6-SIRT3-SERBP1-ferroptosis pathways as a potential new therapeutic target for KSHV-associated cancers.

Despite their rarity (< 4%), when HIV-positive patients with low CD4 count and cholestasis present with AP,tumours should be suspected and evaluated by cross sectional imaging and endoscopic ultrasound.

P=N/A, N=4100, Not yet recruiting, Implenomics | Initiation date: Nov 2023 --> Jul 2024

P2, N=25, Not yet recruiting, AIDS Malignancy Consortium | Trial completion date: Aug 2028 --> Aug 2029 | Initiation date: Jul 2024 --> Jul 2025 | Trial primary completion date: Aug 2026 --> Aug 2028

Many of the differentially expressed genes are regulated by Rel-NF-κB, which regulates immune processes, cell survival, and proliferation and is pivotal to oncogenesis. We thus demonstrate BPTF mutation-mediated monogenic hereditary predilection of KSHV virus-induced oncogenesis, and suggest BPTF as a drug target.

Finally, pacritinib suppressed KSHV viral IL-6-induced human IL-6 and IL-10 production in peripheral blood mononuclear cells, which may model an important step in KSHV-MCD pathogenesis. These results suggest that pacritinib warrants testing for the treatment of KSHV-MCD and PEL.

Correspondingly, genetic depletion or pharmacological inhibition of CDK6 and CAD potently impeded KSHV lytic replication and thwarted tumorigenesis of primary effusion lymphoma (PEL) cells in vitro and in vivo. Altogether, our work defines a viral metabolic reprogramming mechanism underpinning KSHV oncogenesis, which may spur the development of new strategies to treat KSHV-associated malignancies and other diseases.

P4, N=276, Recruiting, Tongji Hospital

P1, N=18, Active, not recruiting, National Cancer Institute (NCI) | Recruiting --> Active, not recruiting

No abstract available

This review consolidates recent findings regarding the expression of LYVE-1 and its functions in lymphangiogenesis during various viral infections and the development of related diseases, with a particular emphasis on Kaposi's sarcoma herpesvirus. Despite the limited available data, it is evident that further studies are essential to comprehensively understand the contribution of LYVE-1 to viral pathogenesis and oncogenesis.

High, and most likely repeated, exposure to SARS-CoV-2 in unvaccinated individuals may have long-term consequences for reactivation of KSHV infection as shown here in the context of HIV-infected patients with impaired immune functions. Post-pandemic prevention and/or monitoring strategies of potential KSHV-associated pathologies in high-risk patients with immunodeficiencies are therefore highly recommended.

Our study exhibited the relationship between CD147 overexpression and recurrence in KS, but the inhomogeneity of the treatment groups and the small number of patients should also be considered. These findings may provide insight into the pathogenesis of KS and the development of targeted therapies in the future.

P1, N=56, Active, not recruiting, National Cancer Institute (NCI) | Recruiting --> Active, not recruiting | N=99 --> 56

We propose a two-pronged model in which interferon-stimulated genes may encode both mRNA and circRNA with antiviral activity. This is critical in cases of host shutoff, such as alpha- and gamma-herpesvirus infection, where the mRNA products are degraded but circRNAs escape.

In addition, the drug-carrying nanocomplex could also significantly reduce the expression of KSHV lytic and latent genes, achieving the purpose of anti-KSHV treatment. In conclusion, these cationic copolymer nanocarriers with PBA targeting possess potential applications in nucleic acid delivery and anti-KSHV therapy.

Our findings strongly indicate that c-Fos plays a crucial role in the promotion of cell proliferation through Notch1 signaling in KSHV-infected cells. Furthermore, our results suggest that the inhibition of expression of key viral pathogenic proteins is likely involved in this process.

The rapid loss of viral genomic DNA was blocked by a lysosomal inhibitor, chloroquine...These observations suggest that LANA may play a role in hiding KSHV episome from innate immune DNA sensors. Our study thus provides new insights into the role of LANA in latency maintenance.

Neighboring terminal repeat (TR) fragments to lytic gene promoters drastically enhanced KSHV replication and transcription activator and LANA transcription regulatory functions. This study, thus, proposes a new latency-lytic switch model in which TR accessibility to the KSHV gene promoters regulates viral inducible gene expression.

P=N/A, N=40, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024

Notably, the DUB activity of OTUD4 is not required for K-RTA stabilization; instead, OTUD4 functions as an adaptor protein to recruit another DUB, USP7, to deubiquitinate K-RTA and facilitate KSHV lytic reactivation. Our study has revealed a novel mechanism whereby KSHV hijacks OTUD4-USP7 deubiquitinases to promote lytic reactivation, which could be potentially harnessed for the development of new antiviral therapies.

At the late stage of lytic replication, KSHV utilizes a mechanism involving RTA to degrade RUNX3, thus evading host inhibition. This finding helps elucidate the regulatory mechanism of the KSHV life cycle and may provide new clues for the development of therapeutic strategies for KSHV-associated diseases.

Finally, we show that ESK-1, a T cell receptor-like monoclonal antibody that recognizes WT1 peptides presented on MHC HLA-A0201, shows increased binding to endothelial cells after KSHV infection or induction of vFLIP expression. We propose that oncogenic isoforms of WT1 are upregulated by KSHV to promote tumorigenesis and that immunotherapy directed against WT1 may be an approach for KS treatment.

Therefore, the DDR mediates KSHV and HSV-1 circularization. This strategy may serve as a general herpesvirus mechanism to initiate latency, and its disruption may provide new opportunities for prevention of herpesvirus disease.

Loss of STAT3 impaired B cell proliferation and differentiation and led to a striking upregulation of interferon-stimulated genes. These findings expand our understanding of STAT3-dependent processes that are key to its function as a pro-viral latency determinant for oncogenic gammaherpesviruses in B cells and may provide novel therapeutic targets.

P1, N=18, Terminated, Fred Hutchinson Cancer Center | N=40 --> 18 | Trial completion date: Dec 2023 --> Jul 2023 | Recruiting --> Terminated | Trial primary completion date: Dec 2023 --> Jul 2023; Closed per SRC Low Accrual Policy

Furthermore, the downregulation of NCL, by way of a short hairpin, showed an increase in LANA translation following an alteration in the levels of LANA mRNA in the cytoplasm. Overall, the data presented in this manuscript showed that G-quadruplexes-mediated translational control could be regulated by NCL, which can be exploited for controlling KSHV latency.

P1, N=8, Terminated, Fred Hutchinson Cancer Center | Active, not recruiting --> Terminated; Terminated due to end of funding

P2, N=26, Active, not recruiting, AIDS Malignancy Consortium | Recruiting --> Active, not recruiting

A common anti-inflammatory agent dexamethasone blocks KSHV-induced hyperinflammation and tumorigenesis by activating glucocorticoid receptor signaling to suppress IL-1α and induce IL-1Ra. This work has identified IL-1-mediated inflammation as a potential therapeutic target and dexamethasone as a potential therapeutic agent for KSHV-induced malignancies.

P2, N=25, Not yet recruiting, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico | Trial completion date: Mar 2029 --> Feb 2030 | Initiation date: Jun 2023 --> Feb 2024 | Trial primary completion date: Mar 2028 --> Feb 2029

Our discovery that the interaction of latency-associated nuclear antigen with HIF1α and NEDD4 inhibits its polyubiquitination activity, which blocks the degradation of RNA Pol II during hypoxia, is a significant contribution to our understanding of KSHV biology. This newfound knowledge provides new leads in the development of novel therapies for KSHV-associated diseases.

The qRT-PCR experiments confirmed that the expression levels of C2CD2L concurred with the results derived from machine learning, but PKNOX1 and APOL3 did not. In summary, we identified a key gene (C2CD2L) that may facilitate the development of biomarkers for insomnia.

This study explored the possible mechanism of G-Rg5 in the treatment of osteosarcoma using network pharmacology method, suggesting that G-Rg5 has the characteristics of multi-targets and multi-pathways in the treatment of osteosarcoma, which lays a foundation for the follow-up experimental and clinical researches on the therapeutic effects of G-Rg5 on osteosarcoma.

He underwent chemotherapy with doxorubicin and showed clinical and laboratory improvement after treatment. CONCLUSIONS Kaposi sarcoma should be considered and investigated in patients with HIV/AIDS who are not on highly active antiretroviral therapy and present with gastrointestinal bleeding as an initial symptom, without any cutaneous lesions.

AIDS-NHL patients are aggressive and have a poor prognosis, and active treatment is needed to improve their long-term survival. Our center prospectively performed autologous HSCT in nine patients with AIDS-NHL, and the results showed that the time of granulocyte and platelet engraftment was consistent with that of ordinary NHL patients, with no transplant-related death and was well tolerated. Failure to achieve complete remission before transplantation may be one of the adverse factors for the early death of patients.

The treatment for Kaposi sarcoma at entry was a bleomycin and vincristine-based regimen in 52% of patients, with a median of 2 cycles (range 1-7)...The remaining 47% received treatment, with the most common regimens being R-Dox (20%), RCHOP (30%), CHOP (30%), Dox-liposomal (10%), and R-Etoposide (10%), with a median of 4 cycles (range 1-7). Eight patients (38%) received ganciclovir maintenance treatment until reaching negative HHV8 viral load...2. Nat Rev Dis 2021 Nov 25; 7(1): 84