Evidence for 2-Methoxyestradiol-Mediated Inhibition of Receptor Tyrosine Kinase RON in the Management of Prostate Cancer.

2-Methoxyestradiol (2-ME) possesses anti-tumorigenic activities in multiple tumor models with acceptable tolerability profile in humans. Incomplete understanding of the mechanism has hindered its development as an anti-tumorigenic compound. We have identified for the first-time macrophage stimulatory protein 1 receptor (MST1R) as a potential target of 2-ME in prostate cancer cells.

Rare osteosarcoma cell subpopulation protein array and profiling using imaging mass cytometry and bioinformatics analysis.

Background: Single rare cell characterization represents a new scientific front in personalized therapy. Imaging mass cytometry (IMC) may be able to address all these questions by combining the power of MS-CyTOF and microscopy.

Methods: We have investigated this IMC method using < 100 to up to 1000 cells from human sarcoma tumor cell lines by incorporating bioinformatics-based t-Distributed Stochastic Neighbor Embedding (t-SNE) analysis of highly multiplexed IMC imaging data.

Cell surface vimentin-positive circulating tumor cell-based relapse prediction in a long-term longitudinal study of postremission neuroblastoma patients.

Neuroblastoma (NB) is a deadly childhood disease that carries a 50% chance of relapse for anyone in remission and similar level of 5-year survival. We investigated the value of our proprietary approach-cell surface vimentin (CSV) positive circulating tumor cells (CTC) to monitor treatment response and predict relapse in NB patients under remission in a Phase II long-term preventative clinical trial. We longitudinally analyzed peripheral blood samples from 93 patients for 27 cycles (~25 months) and discovered that the presence of CSV CTCs in the first two sequential samples (baseline, cycle 4 [month 3-4]) was a significant indicator of earlier relapse.

Discovery of Cell-Surface Vimentin (CSV) as a Sarcoma Target and Development of CSV-Targeted IL12 Immune Therapy.

This chapter discusses a novel target of osteosarcoma (OS), cell-surface vimentin (CSV), and a novel generation of interleukin-12 (IL12), CSV-targeted IL12, for treating OS tumor metastasis. Vimentin is a known intracellular structural protein for mesenchymal cells but is also documented in tumor cells. Our recent study definitively revealed that vimentin can be translocated to the surface of very aggressive tumor cells, such as metastatic cells.

CTC analysis: an update on technological progress.

There is a growing need for a more accurate, real-time assessment of tumor status and the probability of metastasis, relapse, or response to treatment. Conventional means of assessment include imaging and tissue biopsies that can be highly invasive, may not provide complete information of the disease's heterogeneity, and not ideal for repeat analysis. Therefore, a less-invasive means of acquiring similar information at greater time points is necessary.

Cell-surface vimentin-positive macrophage-like circulating tumor cells as a novel biomarker of metastatic gastrointestinal stromal tumors.

The clinical utility of circulating tumor cells (CTCs) has been investigated in numerous publications, but CTCs that express very typical immune cell markers have not been reported. Here we report a novel class of CTCs-CSV-positive macrophage-like CTCs (ML-CTCs). This nomenclature was based on the fact that this class of CTCs can be captured from blood samples of gastrointestinal stromal tumors (GISTs) patients using either the macrophage marker CD68 or our proprietary tumor-specific cell-surface vimentin (CSV) antibody 84-1; likewise, the captured ML-CTCs can be co-stained with both typical macrophage markers (CD14, CD68) and tumor cell markers (DOG-1, C-kit) but not CD45.

Detection of circulating tumor cells from cryopreserved human sarcoma peripheral blood mononuclear cells.

Circulating tumor cells (CTCs) enter the vasculature or lymphatic system after shedding from the primary tumor. CTCs may serve as "seed" cells for tumor metastasis. The utility of CTCs in clinical applications for sarcoma is not fully investigated, partly owing to the necessity for fresh blood samples and the lack of a CTC-specific antibody.

IGF-IR signaling in epithelial to mesenchymal transition and targeting IGF-IR therapy: overview and new insights.

The insulin-like growth factor-I (IGF-I) signaling induces epithelial to mesenchymal transition (EMT) program and contributes to metastasis and drug resistance in several subtypes of tumors. In preclinical studies, targeting of the insulin-like growth factor-I receptor (IGF-IR) showed promising anti-tumor effects. Unfortunately, high expectations for anti-IGF-IR therapy encountered challenge and disappointment in numerous clinical trials.

Regulation of NKG2DCD8 T-cell-mediated antitumor immune surveillance: Identification of a novel CD28 activation-mediated, STAT3 phosphorylation-dependent mechanism.

The natural killer (NK) group 2D (NKG2D) receptor, which displays on mouse and human NK cells, activates CD8 T cells and small subsets of other T cells. NKG2DCD8 T cells play critical roles in both innate and adaptive immunity upon engagement with NKG2D ligands to eliminate tumor and infected cells. Despite the important role of NKG2DCD8 T cells in immune surveillance, the mechanisms of how NKG2D expression on CD8 T cells is regulated remain poorly defined.

Potential role of nuclear PD-L1 expression in cell-surface vimentin positive circulating tumor cells as a prognostic marker in cancer patients.

Although circulating tumor cells (CTCs) have potential as diagnostic biomarkers for cancer, determining their prognostic role in cancer patients undergoing treatment is a challenge. We evaluated the prognostic value of programmed death-ligand 1 (PD-L1) expression in CTCs in colorectal and prostate cancer patients undergoing treatment. Peripheral blood samples were collected from 62 metastatic colorectal cancer patients and 30 metastatic prostate cancer patients.

Recepteur d'origine nantais (RON), more than a kinase: Role in castrate-resistant prostate cancer.

Prostate cancer (PCA) is the second leading cause of cancer-related deaths in men in the United States. It is natural for a hormone-driven malignancy such as prostate cancer that androgen deprivation therapy (ADT) would be the preferred treatment for clinical disease management. However, after initial treatment response a vast majority of patients develop metastatic castrate-resistant prostate cancer (CRPC), which is fatal.

Palmatine inhibits growth and invasion in prostate cancer cell: Potential role for rpS6/NFκB/FLIP.

Novel agents are desperately needed for improving the quality of life and 5-year survival to more than 30% for metastatic castrate-resistant prostate cancer. Previously we showed that Nexrutine, Phellodendron amurense bark extract, inhibits prostate tumor growth in vitro and in vivo. Subsequently using biochemical fractionation we identified butanol fraction contributes to the observed biological activities.