Jungang Chen

Winthrop Rockefeller Foundation

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Zhiqiang Qin

Winthrop Rockefeller Foundation

Lu Dai

Winthrop Rockefeller Foundation

Luis Del Valle

Louisiana Cancer Research Center

Karlie Plaisance‐Bonstaff

Louisiana State University Health Sciences Center New Orleans

Zhen Lin

Tulane University

Lindsey Barrett

University of Arkansas for Medical Sciences

Zhaoxiong Wang

Beihang University

Shengyu Mu

Smith College

Cooperative Institutions

Louisiana Cancer Research Center

Louisiana State University

Louisiana State University Health Sciences Center New Orleans

Winthrop Rockefeller Foundation

University of Arkansas for Medical Sciences

Stanley Foundation

Tulane University

Creative Commons

University of Central Missouri

Peruvian University of Applied Sciences

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Targeting Sphingosine Kinase by ABC294640 against Diffuse Intrinsic Pontine Glioma (DIPG)

Journal of Cancer (2020)

Lu Dai Jungang Chen Zhen Lin Zhaoxiong Wang Shengyu Mu

As a highly aggressive pediatric brainstem tumor, diffuse intrinsic pontine glioma (DIPG) accounts for 10% to 20% of childhood brain tumors.The survival rate for DIPG remains very low, with a median survival time as less than one year even under radiotherapy, the current standard treatment.Moreover, over than 250 clinical trials have failed when trying to improve the survival compared to radiotherapy.The sphingolipid metabolism and related signaling pathways have been found closely related to cancer cell survival; however, the sphingolipid metabolism targeted therapies have never been investigated in DIPG.In the current study, the anti-DIPG activity of ABC294640, the only first-in-class orally available Sphingosine kinase (SphK) inhibitor was explored.Treatment with ABC294640 significantly repressed DIPG cell growth by inducing intracellular pro-apoptotic ceramides production and cell apoptosis.We also profiled ABC294640-induced changes in gene expression within DIPG cells and identified many new genes tightly controlled by sphingolipid metabolism, such as IFITM1 and KAL1.These genes are required for DIPG cell survival and display clinical relevance in DIPG patients' samples.Together, our findings in this study indicate that targeting sphingolipid metabolism may represent a promising strategy to improve DIPG treatment.

Sphingolipid

Sphingosine Kinase

10.7150/jca.46269

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Role of Interleukin-1 Family Members and Signaling Pathways in KSHV Pathogenesis

Frontiers in Cellular and Infection Microbiology (2020)

Lindsey Barrett Jungang Chen Lu Dai Karlie Plaisance‐Bonstaff Luis Del Valle

Kaposi’s sarcoma-associated herpesvirus (KSHV) represents the etiological agent for several human malignancies, including Kaposi’s sarcoma (KS), primary effusion lymphoma (PEL), and multicentric Castleman’s disease (MCD), which are mostly seen in immunocompromised patients. In fact, KSHV has developed many strategies to hijack host immune response, including the regulation of inflammatory cytokine production. Interleukin-1 (IL-1) family represents a major mediator for inflammation and plays an important role in both innate and adaptive immunity. Furthermore, a broadening list of diseases has revealed the pathologic role of IL-1 mediated inflammation. In the current mini-review, we have summarized recent findings about how this oncogenic virus is able to manipulate the activities of IL-1 signaling pathway to facilitate disease progression. We also discuss the therapeutic potential of IL-1 blockade against KSHV-related diseases and several unsolved questions in this interesting field.

Primary effusion lymphoma

Pathogenesis

Mediator

Kaposi's sarcoma-associated herpesvirus

10.3389/fcimb.2020.587929

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Citations (12)