Elevated iNOS and 3′-nitrotyrosine in Kaposi's Sarcoma tumors and mouse model

Vladimirova, Olga; Soldan, Samantha S.; Su, Chenhe; Kossenkov, Andrew V.; Ngalamika, Owen; Tso, For Yue; West, John T.; Wood, Charles; Lieberman, Paul M.

doi:10.1016/j.tvr.2023.200259

Cited by 5 publications

(4 citation statements)

References 35 publications

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“…It is important to recognize that K15 and ORF75 are adjacent genes and K15 is bicistronic [ 45 ]. A recent study also noted elevated ORF75 in three KS skin samples [ 46 ]. The expression analysis presented here suggests that if RNA expression techniques are utilized, additional KSHV genes may represent a more sensitive approach for detecting KS, potentially including ORF72 and ORF75.…”

Section: Discussionmentioning

confidence: 80%

Transcriptional landscape of Kaposi sarcoma tumors identifies unique immunologic signatures and key determinants of angiogenesis

Ramaswami,

Tagawa,

Mahesh

et al. 2023

J Transl Med

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Background Kaposi sarcoma (KS) is a multicentric tumor caused by Kaposi sarcoma herpesvirus (KSHV) that leads to morbidity and mortality among people with HIV worldwide. KS commonly involves the skin but can occur in the gastrointestinal tract (GI) in severe cases. Methods RNA sequencing was used to compare the cellular and KSHV gene expression signatures of skin and GI KS lesions in 44 paired samples from 19 participants with KS alone or with concurrent KSHV-associated diseases. Analyses of KSHV expression from KS lesions identified transcriptionally active areas of the viral genome. Results The transcript of an essential viral lytic gene, ORF75, was detected in 91% of KS lesions. Analyses of host genes identified 370 differentially expressed genes (DEGs) unique to skin KS and 58 DEGs unique to GI KS lesions as compared to normal tissue. Interleukin (IL)-6 and IL-10 gene expression were higher in skin lesions as compared to normal skin but not in GI KS lesions. Twenty-six cellular genes were differentially expressed in both skin and GI KS tissues: these included Fms-related tyrosine kinase 4 (FLT4), encoding an angiogenic receptor, and Stanniocalcin 1 (STC1), a secreted glycoprotein. FLT4 and STC1 were further investigated in functional studies using primary lymphatic endothelial cells (LECs). In these models, KSHV infection of LECs led to increased tubule formation that was impaired upon knock-down of STC1 or FLT4. Conclusions This study of transcriptional profiling of KS tissue provides novel insights into the characteristics and pathogenesis of this unique virus-driven neoplasm.

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Section: Discussionmentioning

confidence: 80%

Transcriptional landscape of Kaposi sarcoma tumors identifies unique immunologic signatures and key determinants of angiogenesis

Ramaswami,

Tagawa,

Mahesh

et al. 2023

J Transl Med

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“…The experimental results imply that these compounds have the ability to autonomously establish a stable binding state with potential target proteins via the active sites, influencing downstream signaling pathways and exerting their physiological functions. However, considering the crucial role of docking proteins in inflammatory diseases, tumors, and cardiovascular diseases [ 38 , 39 , 40 ], it is necessary to further explore the roles played by these three antioxidants in disease control via more rigorous pharmacological experiments in subsequent studies.…”

Section: Discussionmentioning

confidence: 99%

Separation of Antioxidants from Trace Fraction of Ribes himalense via Chromatographic Strategy and Their Antioxidant Activity Supported with Molecular Simulations

Liu,

Lei

et al. 2023

IJMS

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Antioxidants from natural sources have long been of interest to researchers. In this paper, taking the traditional Tibetan medicine Ribes himalense as an example, an integrated approach was used to identify and isolate its chemical composition with free-radical-scavenging properties from its ethanol extract. First, the ethanol extract of Ribes himalense was pretreated using polyamide medium-pressure liquid chromatography (polyamide-MPLC), and the target fraction (Fr4) was obtained. Then, a combined HPLC mode was utilized to purify antioxidants in Fr4 under the guidance of an online HPLC-1,1-diphenyl-2-picrylhydrazyl (HPLC-DPPH) activity screening system. Finally, three antioxidants (3-caffeoylquinic acid methyl ester, rutin, and myricetin-3′-α-L-rhamnopyranoside) were isolated, and this is the first report of their presence in R. himalense. Further molecular docking studies showed that the antioxidants exhibited good binding with HO-1, Nrf2, and iNOS. In conclusion, this comprehensive approach is capable of extracting high-purity antioxidants from trace fractions of Ribes himalense and holds promise for future applications in the exploration of the chemical compositions and bioactivity of natural products.

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“…High demand for ATP and increased levels of reactive oxygen species (ROS), together with hypoxic conditions in tumor tissue, lead to the Warburg effect, a balancing act involving glycolysis generating ATP and the pentose phosphate pathway (PPP) maintaining reducing power together with supplying precursors for purine metabolism [ 36 ]. Cancer cells exhibit higher levels of ROS production and consequently increased levels of ROS scavenging [ 40 ]. Trehalose, detected as differentially increased in KSHV + /HIV + versus KSHV + HIV − plasma, is well known for its antioxidant properties with anti-inflammatory and cancer-inhibitory effects [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

Comparative polar and lipid plasma metabolomics differentiate KSHV infection and disease states

Privatt,

Braga,

Johnson

et al. 2023

Cancer Metab

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Background Kaposi sarcoma (KS) is a neoplastic disease etiologically associated with infection by the Kaposi sarcoma-associated herpesvirus (KSHV). KS manifests primarily as cutaneous lesions in individuals due to either age (classical KS), HIV infection (epidemic KS), or tissue rejection preventatives in transplantation (iatrogenic KS) but can also occur in individuals, predominantly in sub-Saharan Africa (SSA), lacking any obvious immune suppression (endemic KS). The high endemicity of KSHV and human immunodeficiency virus-1 (HIV) co-infection in Africa results in KS being one of the top 5 cancers there. As with most viral cancers, infection with KSHV alone is insufficient to induce tumorigenesis. Indeed, KSHV infection of primary human endothelial cell cultures, even at high levels, is rarely associated with long-term culture, transformation, or growth deregulation, yet infection in vivo is sustained for life. Investigations of immune mediators that distinguish KSHV infection, KSHV/HIV co-infection, and symptomatic KS disease have yet to reveal consistent correlates of protection against or progression to KS. In addition to viral infection, it is plausible that pathogenesis also requires an immunological and metabolic environment permissive to the abnormal endothelial cell growth evident in KS tumors. In this study, we explored whether plasma metabolomes could differentiate asymptomatic KSHV-infected individuals with or without HIV co-infection and symptomatic KS from each other. Methods To investigate how metabolic changes may correlate with co-infections and tumorigenesis, plasma samples derived from KSHV seropositive sub-Saharan African subjects in three groups, (A) asymptomatic (lacking neoplastic disease) with KSHV infection only, (B) asymptomatic co-infected with KSHV and HIV, and (C) symptomatic with clinically diagnosed KS, were subjected to analysis of lipid and polar metabolite profiles Results Polar and nonpolar plasma metabolic differentials were evident in both comparisons. Integration of the metabolic findings with our previously reported KS transcriptomics data suggests dysregulation of amino acid/urea cycle and purine metabolic pathways, in concert with viral infection in KS disease progression. Conclusions This study is, to our knowledge, the first to report human plasma metabolic differentials between in vivo KSHV infection and co-infection with HIV, as well as differentials between co-infection and epidemic KS.

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Elevated iNOS and 3′-nitrotyrosine in Kaposi's Sarcoma tumors and mouse model

Cited by 5 publications

References 35 publications

Transcriptional landscape of Kaposi sarcoma tumors identifies unique immunologic signatures and key determinants of angiogenesis

Transcriptional landscape of Kaposi sarcoma tumors identifies unique immunologic signatures and key determinants of angiogenesis

Separation of Antioxidants from Trace Fraction of Ribes himalense via Chromatographic Strategy and Their Antioxidant Activity Supported with Molecular Simulations

Comparative polar and lipid plasma metabolomics differentiate KSHV infection and disease states

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