Project description:Metastatic (as well as tumor) microenvironments contain both cancer-promoting as well as cancer restraining factors. The balance between these opposing forces determines the fate of cancer cells that disseminate to secondary organ sites. In search for microenvironmental drivers or inhibitors of metastasis, we identified, in a previous study, the beta subunit of hemoglobin (HBB) as a lung-derived antimetastatic factor. In the present study, exploring mechanisms leading to melanoma brain metastasis, we discovered that brain-derived factors restrain proliferation and induce apoptosis and necrosis of brain-metastasizing melanoma cells. Employing various purification procedures, we identified a heterodimer composed of hemoglobin alpha and beta chains that performs these anti-metastatic functions. Neither the alpha nor the beta subunit alone were inhibitory. An alpha/beta chain dimer chemically purified from human hemoglobin inhibited the cell viability of primary melanomas, melanoma brain metastasis (MBM), and breast cancer cell lines. The dimer-induced DNA damage, cell cycle arrest at the SubG1 phase, apoptosis, and significant necrosis in four MBM cell lines. Proteomic analysis of dimer-treated MBM cells revealed that the dimer downregulates the expression of BRD4, GAB2, and IRS2 proteins playing crucial roles in cancer cell sustainability and progression.
Project description:Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a significant adverse effect of paclitaxel in patients with breast cancer. However, reliable biomarkers for early detection and monitoring of CIPN are lacking.Methods: We investigated neurofilament light chain (NfL) and galectin-3 as candidate biomarkers for CIPN, and performed proteomic analysis to identify novel molecular contributors in two cohorts of patients with breast cancer undergoing paclitaxel therapy. Blood samples were collected longitudinally to measure NfL and galectin-3 levels. Differentially expressed proteins associated with CIPN onset were identified by proteomics.Results: NfL levels significantly increased in patients with CIPN, from as early as 3 weeks after treatment initiation. NfL levels were markedly higher in patients with vs. without CIPN. There were no changes or between-group differences in galectin-3 levels. Proteomic analysis identified upregulation of alcohol dehydrogenase 4 (ADH4) and downregulation of vesicular overexpressed in cancer prosurvival protein 1 (VOPP1) in CIPN, implicating oxidative stress and disrupted mitochondrial dynamics in the pathogenesis of CIPN.Conclusion: NfL represents a candidate biomarker for early detection of CIPN, and we identified proteins potentially associated with the development of CIPN. Our findings provide further insights into the pathogenesis of CIPN. Integrating biomarkers and proteomics paves the way for precision medicine to manage chemotherapy-induced toxicities.
Project description:The TeloVac study indicated that GV1001 did not to improve the survival of advanced pancreatic ductal adenocarcinoma (PDAC) patients. However, the cytokine examinations of the study suggested that high serum eotaxin levels may predict responses to GV1001. This phase III trial aimed to assess the efficacy of GV1001 with gemcitabine/capecitabine for eotaxin-high patients with untreated locally advanced and metastatic PDAC. In addition, we proposed potential blood markers to predict response to GV1001 treatment based on correlative studies.
Project description:To identify differentially phosphorylated proteins between wild-type and Pak1-deficient mouse breast cancer cells, we performed a comparative study by using phospho-antibody arrays.
Project description:In this study, we describe the development and use of an ad hoc protein microarray to study the immune response induced by the three major 4CMenB antigenic components (fHbp, NHBA and NadA) in individual sera from vaccinated infants, adolescents and adults.
Project description:Comparing between plasma cytokine proteins on AML patients with or without aGVHD Comparing between plasma cytokine proteins on AML patients with or without aGVHD after allogeneic hematopoietic stem cell transplantation, Day+14
Project description:Increasing evidence suggests that antibodies (Abs) can have protective roles in M. tuberculosis (Mtb) infection but knowledge of the most relevant protective antigens and epitopes in humans is limited. Using novel glycan arrays, we establish that human serum IgG induced against the M. tuberculosis (Mtb) capsular polysacharide arabinomannan (AM) in natural Mtb infection is highly heterogeneous in its binding specificity and differs in both its reactivity to oligosaccharide (OS) motifs within AM and its functions between BCG vaccination and/or controlled (latent) versus uncontrolled (TB) M. tuberculosis infection. We show that anti-AM IgG from asymptomatic but not diseased individuals is protective, and provide data suggesting a role of IgG2 and specific AM oligosaccharides. Filling a gap in the current knowledge of protective antigens in humans, our human data support the key role of the M. tuberculosis surface glycan AM and suggest the importance of targeting specific glycan epitopes within AM in antibody-mediated immunity against TB.
Project description:Examine protein phosphorylation status during peripheral nerve regeneration when using autologous nerve graft or tissue engineered nerve graft to bridge nerve gap.