Scientific Publications

Multiple myeloma (MM) is a cancer of plasma cells caused by abnormal gene expression and interactions within the bone marrow (BM) niche. The BM environment significantly influences the progression of MM. Celastrol, a natural compound derived from traditional Chinese medicine, exhibits significant anticancer effects. This study aimed to identify specific targets of celastrol and develop more effective and less toxic treatment options for MM. Celastrol is used as a probe to determine its specific target, pyridoxine-5′-phosphate oxidase (PNPO). Increased levels of PNPO are associated with poor outcomes in MM patients, and PNPO promotes MM cell proliferation and induces osteoclast differentiation through exosomes.

• Link: https://advanced.onlinelibrary.wiley.com/doi/10.1002/advs.202407681

Autoantibodies hold promise for diagnosing lung cancer. However, their effectiveness in early-stage detection needs improvement. In this study, we investigated novel IgG and IgM autoantibodies for detecting early-stage lung adenocarcinoma (Early-LUAD) by employing a multi-step approach, including Human Proteome Microarray (HuProtTM) discovery, focused microarray verification, and ELISA validation, on 1246 individuals consisting of 634 patients with Early-LUAD (stage 0–I), 280 patients with benign lung disease (BLD), and 332 normal healthy controls (NHCs). HuProtTM selected 417 IgG/IgM candidates, and focused microarray further verified 55 significantly elevated IgG/IgM autoantibodies targeting 32 tumor-associated antigens in Early-LUAD compared to BLD/NHC/BLD+NHC.

• Link: https://academic.oup.com/gpb/article/22/6/qzae085/7921422

This report demonstrates that current technologies are able to observe multi-isotype subpopulations within proteome-wide autoantibody seromic profiles. Seromics, the high-throughput mapping and characterization of antigen reactivity from the totality of the secreted antibody repertoire in serum and bodily fluids, was first used in literature by Gnjatic et. al in 2010.1 According to a co-author of the study, this term was coined by none other than Lloyd Old. In the decade plus since that time, the role of B cell responses in cancer immunotherapy has been hotly debated – with data supporting both positive and negative patient outcomes.

• Link: https://jitc.bmj.com/content/12/Suppl_2/A45

Immune checkpoint blockers (ICBs) revolutionized the treatment of patients with advanced non-small cell lung cancer (NSCLC) but only a fraction of them obtain a response, and clinical benefit from these treatments is often difficult to predict. The aim of our study is to unveil the potential implications of antibody response to previous viral infections in predicting response to ICBs in patients with NSCLC.

• Link: https://jitc.bmj.com/content/12/11/e009931

Background: Increasing evidence suggests that E3 ubiquitin ligases are key regulatory factors involved in cancer progression. While members of the DTX family of E3 ubiquitin ligases have been reported in various cancers, the role and molecular mechanisms of its important member, DTX3L, in the progression of renal cell carcinoma remain unexplored.

• Link: https://papers.ssrn.com/sol3/papers.cfm?abstract_id=4982191

Nomilin is a limonoid compound known for its multiple biological activities, but its role in triple negative breast cancer (TNBC) remains unclear. This study aims to uncover the potential therapeutic effect of nomilin on TNBC and elucidate the specific mechanism of its action.

• Link: https://molmed.biomedcentral.com/articles/10.1186/s10020-024-00928-2

Accumulating evidence has proved the close association between alterations in gut microbiota and resistance to chemotherapeutic drugs. However, the potential roles of gut microbiota in regulating oxaliplatin sensitivity in gastric cancer (GC) have not been investigated before. We first found that antibiotic treatment diminished the therapeutic efficacy of oxaliplatin in a GC mouse model. Importantly, this effect could be transmitted to germ-free mice via fecal microbiota transplantation, indicating a potential role of gut microbiota modulation in oxaliplatin efficacy.

• Link: https://www.sciencedirect.com/science/article/pii/S1043661824002238?via%3Dihub

Isochlorate dehydrogenase 1 (IDH1) is an important metabolic enzyme for the production of α-ketoglutarate (α-KG), which has antitumor effects and is considered to have potential antitumor effects. The activation of IDH1 as a pathway for the development of anticancer drugs has not been attempted. We demonstrated that IDH1 can limit glycolysis in hepatocellular carcinoma (HCC) cells to activate the tumor immune microenvironment. In addition, through proteomic microarray analysis, we identified a natural small molecule, scutellarin (Scu), which activates IDH1 and inhibits the growth of HCC cells. By selectively modifying Cys297, Scu promotes IDH1 active dimer formation and increases α-KG production, leading to ubiquitination and degradation of HIF1a.

• Link: https://www.nature.com/articles/s41419-024-06625-6

Intra-tumoral B cells mediate a plethora of immune effector mechanisms with key roles in anti-tumor immunity and serve as positive prognostic indicators in a variety of solid tumor types, including epithelial ovarian cancer (EOC). Several aspects of intra-tumoral B cells remain unclear, such as their state of activation, antigenic repertoires, and capacity to mature into plasma cells.

• Link: https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1379175/full

Doxorubicin (DOX) is an effective anticancer agent, but its clinical utility is constrained by dose-dependent cardiotoxicity, partly due to cardiomyocyte ferroptosis. However, the progress of developing cardioprotective medications to counteract ferroptosis has encountered obstacles. Protosappanin A (PrA), an anti-inflammatory compound derived from hematoxylin, shows potential against DOX-induced cardiomyopathy (DIC). Here, it is reported that PrA alleviates myocardial damage and dysfunction by reducing DOX-induced ferroptosis and maintaining mitochondrial homeostasis.

• Link: https://onlinelibrary.wiley.com/doi/10.1002/advs.202310227