scholarly journals Fluorescence monitoring of rare circulating tumor cell and cluster dissemination in a multiple myeloma xenograft model in vivo

2019 ◽  
Vol 24 (08) ◽  
pp. 1 ◽  
Author(s):  
Roshani Patil ◽  
Xuefei Tan ◽  
Peter Bartosik ◽  
Alexandre Detappe ◽  
Judith M. Runnels ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Tumor Cell ◽  
Xenograft Model ◽  
Circulating Tumor Cell

scholarly journals In Vivo Monitoring of Rare Circulating Tumor Cell and Cluster Dissemination in a Multiple Myeloma Xenograft Model

2019 ◽  
Author(s):  
Roshani Patil ◽  
Xuefei Tan ◽  
Peter Bartosik ◽  
Alexandre Detappe ◽  
Judith Runnels ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Tumor Cell ◽  
Fluorescent Protein ◽  
Xenograft Model ◽  
Circulating Tumor Cell ◽  
Hematogenous Metastasis ◽  
Circulating Cells ◽  
Green Fluorescent ◽  
First Time

AbstractWe recently developed ‘Diffuse in vivo Flow Cytometry’ (DiFC), a new pre-clinical research tool for enumerating extremely rare fluorescently-labeled circulating cells directly in vivo. In this paper, we developed a green fluorescent protein (GFP) compatible version of DiFC, and used it to non-invasively monitor the circulating tumor cell (CTC) burden over time in a multiple myeloma disseminated xenograft model. We show that DiFC allowed counting of CTCs at estimated concentrations below 1 cell per mL in peripheral blood with a negligible false alarm rate. DiFC also revealed the presence of CTC clusters in circulation to our knowledge for the first time in this model, and allowed us to calculate their size, kinetics, and frequency of shedding. We anticipate that the unique capabilities of DiFC will have many applications in the study of hematogenous metastasis, and as a powerful complementary methodology to liquid biopsy assays.

Real-time monitoring of circulating tumor cell release during tumor manipulation using in vivo photoacoustic and fluorescent flow cytometry

Head & Neck ◽  
2013 ◽  
Vol 36 (8) ◽  
pp. 1207-1215 ◽  
Author(s):  
Mazen A. Juratli ◽  
Mustafa Sarimollaoglu ◽  
Eric R. Siegel ◽  
Dmitry A. Nedosekin ◽  
Ekaterina I. Galanzha ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Tumor Cell ◽  
Real Time ◽  
Circulating Tumor Cell ◽  
Real Time Monitoring ◽  
Cell Release

scholarly journals Construction and Clinical Verification of Cytoplasm Protein GFAP as Circulating Tumor Cell Separation target for Pediatric Neuroepithelial Tumors

2020 ◽  
Author(s):  
Yang Zhao ◽  
Feng Jiang ◽  
Qinhua Wang ◽  
Baocheng Wang ◽  
Yipeng Han ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Detection System ◽  
Invasive Procedure ◽  
Circulating Tumor Cell ◽  
Immunofluorescence Assay ◽  
Good Choice ◽  
Neuroepithelial Tumors ◽  
Prediction Function

Abstract BACKGROUND: Pediatric Neuroepithelial Tumors (NT) are one of the most prevalent diseases among children. Developing a highly efficient cerebrospinal fluid (CSF) detection system with diagnosis and prediction function is very important. Circulating tumor cell (CTC) in CSF is a good choice. In contrast to the past use of epithelial EpCAM as CTC separation target, an cytoplasm protein of GFAP antibody was first selected to construct highly-sensitive immunomagnetic liposomes (IMLs). The validation and efficiency of this system in capturing CTCs for NT were measured both in vitro and in vivo. The associations between the numbers of CTCs in patients with their clinical characteristics were further analyzed. RESULTS: Our data show that CTCs can be successfully isolated from CSF and blood samples from 29 children with NT. The numbers of CTCs in CSF were significantly higher than those in blood. The level of CTCs in CSF was related to the type and location of the tumor rather than its stage. Genetic testing in GFAP CTC-DNA by sanger sequencing, q-PCR and NGS methods indicated that the isolated CTCs (GFAP+/EGFR+) are the related tumor cell. For example, the high expression of NPR3 gene in CSF CTC was consistant with tumor tissue. CONCLUSIONS: GFAP-IML isolation of CTCs, combined with an EGFR immunofluorescence assay of antitumor marker, can serve as a brand-new method for the identification of CTCs for brain tumors. Via lumbar puncture, a minimally invasive procedure, this technique can be clinically significant in diagnosis and efficacy assessments of pediatric NT.

scholarly journals Tumor Cell Gene Expression Changes Following Short-term In vivo Exposure to Single Agent Chemotherapeutics are Related to Survival in Multiple Myeloma

2008 ◽  
Vol 14 (15) ◽  
pp. 4821-4829 ◽  
Author(s):  
Bart Burington ◽  
Bart Barlogie ◽  
Fenghuang Zhan ◽  
John Crowley ◽  
John D. Shaughnessy
Keyword(s):  
Gene Expression ◽  
Multiple Myeloma ◽  
Tumor Cell ◽  
Single Agent ◽  
Short Term ◽  
Cell Gene Expression ◽  
Cell Gene

scholarly journals A novel BCMA/CD3 bispecific T-cell engager for the treatment of multiple myeloma induces selective lysis in vitro and in vivo

Leukemia ◽  
2016 ◽  
Vol 31 (8) ◽  
pp. 1743-1751 ◽  
Author(s):  
S Hipp ◽  
Y-T Tai ◽  
D Blanset ◽  
P Deegen ◽  
J Wahl ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
T Cell ◽  
Plasma Cells ◽  
Ex Vivo ◽  
Xenograft Model ◽  
Selective Lysis ◽  
Bispecific T Cell Engager

Abstract B-cell maturation antigen (BCMA) is a highly plasma cell-selective protein that is expressed on malignant plasma cells of multiple myeloma (MM) patients and therefore is an ideal target for T-cell redirecting therapies. We developed a bispecific T-cell engager (BiTE) targeting BCMA and CD3ɛ (BI 836909) and studied its therapeutic impacts on MM. BI 836909 induced selective lysis of BCMA-positive MM cells, activation of T cells, release of cytokines and T-cell proliferation; whereas BCMA-negative cells were not affected. Activity of BI 836909 was not influenced by the presence of bone marrow stromal cells, soluble BCMA or a proliferation-inducing ligand (APRIL). In ex vivo assays, BI 836909 induced potent autologous MM cell lysis in both, newly diagnosed and relapsed/refractory patient samples. In mouse xenograft studies, BI 836909 induced tumor cell depletion in a subcutaneous NCI-H929 xenograft model and prolonged survival in an orthotopic L-363 xenograft model. In a cynomolgus monkey study, administration of BI 836909 led to depletion of BCMA-positive plasma cells in the bone marrow. Taken together, these results show that BI 836909 is a highly potent and efficacious approach to selectively deplete BCMA-positive MM cells and represents a novel immunotherapeutic for the treatment of MM.

scholarly journals Combination of proteasome inhibitors bortezomib and NPI-0052 trigger in vivo synergistic cytotoxicity in multiple myeloma

Blood ◽  
2008 ◽  
Vol 111 (3) ◽  
pp. 1654-1664 ◽  
Author(s):  
Dharminder Chauhan ◽  
Ajita Singh ◽  
Mohan Brahmandam ◽  
Klaus Podar ◽  
Teru Hideshima ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Proteasome Inhibitors ◽  
Xenograft Model ◽  
Er Stress Response ◽  
Synergistic Cytotoxicity ◽  
Proteolytic Activities ◽  
Dose Combination ◽  
Inhibition Of Tumor Growth

AbstractOur recent study demonstrated that a novel proteasome inhibitor NPI-0052 triggers apoptosis in multiple myeloma (MM) cells, and importantly, that is distinct from bortezomib (Velcade) in its chemical structure, effects on proteasome activities, and mechanisms of action. Here, we demonstrate that combining NPI-0052 and bortezomb induces synergistic anti-MM activity both in vitro using MM cell lines or patient CD138+ MM cells and in vivo in a human plasmacytoma xenograft mouse model. NPI-0052 plus bortezomib–induced synergistic apoptosis is associated with: (1) activation of caspase-8, caspase-9, caspase-3, and PARP; (2) induction of endoplasmic reticulum (ER) stress response and JNK; (3) inhibition of migration of MM cells and angiogenesis; (4) suppression of chymotrypsin-like (CT-L), caspase-like (C-L), and trypsin-like (T-L) proteolytic activities; and (5) blockade of NF-κB signaling. Studies in a xenograft model show that low dose combination of NPI-0052 and bortezomib is well tolerated and triggers synergistic inhibition of tumor growth and CT-L, C-L, and T-L proteasome activities in tumor cells. Immununostaining of MM tumors from NPI-0052 plus bortezomib–treated mice showed growth inhibition, apoptosis, and a decrease in associated angiogenesis. Taken together, our study provides the preclinical rationale for clinical protocols evaluating bortezomib together with NPI-0052 to improve patient outcome in MM.

scholarly journals Identification of a novel c-Myc inhibitor with antitumor effects on multiple myeloma cells

2018 ◽  
Vol 38 (5) ◽  
Author(s):  
Ruosi Yao ◽  
Xiaoyang Sun ◽  
Yu Xie ◽  
Xiaoshen Sun ◽  
Yao Yao ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Xenograft Model ◽  
Molecular Compound ◽  
Severe Combined Immune Deficiency ◽  
Antitumor Effects ◽  
Mouse Xenograft Model ◽  
The Stability ◽  
Rpmi 8226

Increasing evidence shows that c-Myc oncoprotein is tightly associated with multiple myeloma (MM) progression. Herein, we identified compound 7594-0035, which is a novel inhibitor that specifically targets c-Myc. It was identified from the ChemDiv compound database by molecular docking-based, high-throughput virtual screening. Compound 7594-0035 inhibited MM cell proliferation in vitro, induced cell cycle G2-phase arrest, and triggered MM cell death by disturbing the stability of c-Myc protein. Additionally, we also found that compound 7594-0035 overcame bortezomib (BTZ) drug resistance and increased the killing effect on MM cells in combination with BTZ. The severe combined immune deficiency (SCID) mouse xenograft model revealed that compound 7594-0035 partially decreased the primary tumor growth of Roswell Park Memorial Institute (RPMI)-8226 cells in vivo. The novel small molecular compound 7594-0035 described in the present study that targets c-Myc protein is likely to be a promising therapeutic agent for relapsed/refractory MM.

Green tea polyphenols block the anticancer effects of bortezomib and other boronic acid–based proteasome inhibitors

Blood ◽  
2009 ◽  
Vol 113 (23) ◽  
pp. 5927-5937 ◽  
Author(s):  
Encouse B. Golden ◽  
Philip Y. Lam ◽  
Adel Kardosh ◽  
Kevin J. Gaffney ◽  
Enrique Cadenas ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Cell Death ◽  
Tumor Cell ◽  
Green Tea ◽  
Boronic Acid ◽  
Proteasome Inhibitors ◽  
Green Tea Polyphenols ◽  
Tumor Cell Death

Abstract The anticancer potency of green tea and its individual components is being intensely investigated, and some cancer patients already self-medicate with this “miracle herb” in hopes of augmenting the anticancer outcome of their chemotherapy. Bortezomib (BZM) is a proteasome inhibitor in clinical use for multiple myeloma. Here, we investigated whether the combination of these compounds would yield increased antitumor efficacy in multiple myeloma and glioblastoma cell lines in vitro and in vivo. Unexpectedly, we discovered that various green tea constituents, in particular (-)-epigallocatechin gallate (EGCG) and other polyphenols with 1,2-benzenediol moieties, effectively prevented tumor cell death induced by BZM in vitro and in vivo. This pronounced antagonistic function of EGCG was evident only with boronic acid–based proteasome inhibitors (BZM, MG-262, PS-IX), but not with several non–boronic acid proteasome inhibitors (MG-132, PS-I, nelfinavir). EGCG directly reacted with BZM and blocked its proteasome inhibitory function; as a consequence, BZM could not trigger endoplasmic reticulum stress or caspase-7 activation, and did not induce tumor cell death. Taken together, our results indicate that green tea polyphenols may have the potential to negate the therapeutic efficacy of BZM and suggest that consumption of green tea products may be contraindicated during cancer therapy with BZM.

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