scholarly journals 18FDG, [18F]FLT, [18F]FAZA, and11C-Methionine Are Suitable Tracers for the Diagnosis andIn VivoFollow-Up of the Efficacy of Chemotherapy by miniPET in Both Multidrug Resistant and Sensitive Human Gynecologic Tumor Xenografts

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
György Trencsényi ◽  
Teréz Márián ◽  
Imre Lajtos ◽  
Zoltán Krasznai ◽  
László Balkay ◽  
...  
Keyword(s):  
Combined Treatment ◽  
Human Tumor ◽  
Multidrug Resistant ◽  
Tumor Xenograft ◽  
Human Tumor Xenograft ◽  
Tumor Xenografts ◽  
Gynecologic Tumor ◽  
Human Ovarian Carcinoma

Expression of multidrug pumps including P-glycoprotein (MDR1, ABCB1) in the plasma membrane of tumor cells often results in decreased intracellular accumulation of anticancer drugs causing serious impediment to successful chemotherapy. It has been shown earlier that combined treatment with UIC2 anti-Pgp monoclonal antibody (mAb) and cyclosporine A (CSA) is an effective way of blocking Pgp function. In the present work we investigated the suitability of four PET tumor diagnostic radiotracers including 2-[18F]fluoro-2-deoxy-D-glucose (18FDG),11C-methionine, 3′-deoxy-3′-[18F]fluorothymidine (18F-FLT), and [18F]fluoroazomycin-arabinofuranoside (18FAZA) forin vivofollow-up of the efficacy of chemotherapy in both Pgp positive (Pgp+) and negative (Pgp−) human tumor xenograft pairs raised in CB-17 SCID mice. Pgp+and Pgp−A2780AD/A2780 human ovarian carcinoma and KB-V1/KB-3-1 human epidermoid adenocarcinoma tumor xenografts were used to study the effect of the treatment with an anticancer drug doxorubicin combined with UIC2 and CSA. The combined treatment resulted in a significant decrease of both the tumor size and the accumulation of the tumor diagnostic tracers in the Pgp+tumors. Our results demonstrate that18FDG,18F-FLT,18FAZA, and11C-methionine are suitable PET tracers for the diagnosis andin vivofollow-up of the efficacy of tumor chemotherapy in both Pgp+and Pgp−human tumor xenografts by miniPET.

scholarly journals Force estimation from 4D OCT data in a human tumor xenograft mouse model

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Maximilian Neidhardt ◽  
Nils Gessert ◽  
Tobias Gosau ◽  
Julia Kemmling ◽  
Susanne Feldhaus ◽  
...  
Keyword(s):  
Deep Learning ◽  
Mouse Model ◽  
Haptic Feedback ◽  
Human Tumor ◽  
Tumor Xenograft ◽  
Human Tumor Xenograft ◽  
Force Estimation ◽  
Xenograft Mouse Model ◽  
Dead Tissue

AbstractMinimally invasive robotic surgery offer benefits such as reduced physical trauma, faster recovery and lesser pain for the patient. For these procedures, visual and haptic feedback to the surgeon is crucial when operating surgical tools without line-of-sight with a robot. External force sensors are biased by friction at the tool shaft and thereby cannot estimate forces between tool tip and tissue. As an alternative, vision-based force estimation was proposed. Here, interaction forces are directly learned from deformation observed by an external imaging system. Recently, an approach based on optical coherence tomography and deep learning has shown promising results. However, most experiments are performed on ex-vivo tissue. In this work, we demonstrate that models trained on dead tissue do not perform well in in vivo data. We performed multiple experiments on a human tumor xenograft mouse model, both on in vivo, perfused tissue and dead tissue. We compared two deep learning models in different training scenarios. Training on perfused, in vivo data improved model performance by 24% for in vivo force estimation.

scholarly journals Direct in vivo measurement of targeted binding in a human tumor xenograft

1997 ◽  
Vol 94 (5) ◽  
pp. 1785-1790 ◽  
Author(s):  
D. A. Berk ◽  
F. Yuan ◽  
M. Leunig ◽  
R. K. Jain
Keyword(s):  
Human Tumor ◽  
Tumor Xenograft ◽  
Human Tumor Xenograft ◽  
In Vivo Measurement

Development of an orthotopic SCID mouse-human tumor xenograft model displaying the multidrug-resistant phenotype

1996 ◽  
Vol 37 (4) ◽  
pp. 305-316 ◽  
Author(s):  
W. T. Bellamy ◽  
Pamela Mendibles ◽  
Petra Bontje ◽  
Floyd Thompson ◽  
Lynne Richter ◽  
...  
Keyword(s):  
Scid Mouse ◽  
Xenograft Model ◽  
Human Tumor ◽  
Multidrug Resistant ◽  
Tumor Xenograft ◽  
Human Tumor Xenograft ◽  
Resistant Phenotype ◽  
Human Tumor Xenograft Model

Pralatrexate-induced tumor cell apoptosis in the epidermis of a patient with HTLV-1 adult T-cell lymphoma/leukemia causing skin erosions

Blood ◽  
2009 ◽  
Vol 113 (25) ◽  
pp. 6338-6341 ◽  
Author(s):  
Alexander G. Marneros ◽  
Marc E. Grossman ◽  
David N. Silvers ◽  
Sameera Husain ◽  
Gerard J. Nuovo ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Lymphoma ◽  
Human Tumor ◽  
Clinical Decision ◽  
T Cell Lymphoma ◽  
Response To Treatment ◽  
Tumor Xenograft ◽  
Human Tumor Xenograft ◽  
Unaffected Skin

Abstract Pralatrexate is a novel antifolate, which shows increased antitumor activity in human tumor xenograft studies in mice compared with methotrexate. We investigated the effects of pralatrexate in a patient with adult T-cell lymphoma/leukemia with significant skin involvement. Atypical lymphocytes in epidermal Pautrier microabscesses were positive for HTLV-1. After the patient presented with leukemic conversion and with worsening of an erythematous generalized papular rash, he received one dose of pralatrexate. Within one week, his skin developed innumerable small erosions limited to the areas of the papular rash, sparing unaffected skin. Here we present in vivo evidence that pralatrexate-induced erosions in skin affected by adult T-cell lymphoma/leukemia are a manifestation of apoptosis of tumor cells infiltrating the epidermis and are not the result of cytotoxicity by pralatrexate on keratinocytes. This distinction is critical and may profoundly influence the clinical decision to continue pralatrexate treatment. Pralatrexate-induced skin erosions may indicate response to treatment.

scholarly journals Targeting the myeloid checkpoint receptor SIRPα potentiates innate and adaptive immune responses to promote anti-tumor activity

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Tracy C. Kuo ◽  
Amy Chen ◽  
Ons Harrabi ◽  
Jonathan T. Sockolosky ◽  
Anli Zhang ◽  
...  
Keyword(s):  
T Cell ◽  
Mononuclear Cells ◽  
Regulatory Protein ◽  
Human Tumor ◽  
Tumor Xenograft ◽  
Hematological Toxicity ◽  
Human Tumor Xenograft ◽  
Cynomolgus Monkeys

Abstract Background Signal regulatory protein α (SIRPα) is a myeloid-lineage inhibitory receptor that restricts innate immunity through engagement of its cell surface ligand CD47. Blockade of the CD47–SIRPα interaction synergizes with tumor-specific antibodies and T-cell checkpoint inhibitors by promoting myeloid-mediated antitumor functions leading to the induction of adaptive immunity. Inhibition of the CD47–SIRPα interaction has focused predominantly on targeting CD47, which is expressed ubiquitously and contributes to the accelerated blood clearance of anti-CD47 therapeutics. Targeting SIRPα, which is myeloid-restricted, may provide a differential pharmacokinetic, safety, and efficacy profile; however, SIRPα polymorphisms and lack of pan-allelic and species cross-reactive agents have limited the clinical translation of antibodies against SIRPα. Here, we report the development of humanized AB21 (hAB21), a pan-allelic anti-SIRPα antibody that binds human, cynomolgus monkey, and mouse SIRPα alleles with high affinity and blocks the interaction with CD47. Methods Human macrophages derived from donors with various SIRPα v1 and v2 allelic status were used to assess the ability of hAB21 to enhance phagocytosis. HAB21_IgG subclasses were evaluated for targeted depletion of peripheral blood mononuclear cells, phagocytosis and in vivo efficacy in xenograft models. Combination therapy with anti-PD1/anti-PD-L1 in several syngeneic models was performed. Immunophenotyping of tissues from MC38 tumor-bearing mice treated with AB21 and anti-PD-1 was evaluated. PK, PD and tolerability of hAB21 were evaluated in cynomolgus monkeys. Results SIRPα blockade with hAB21 promoted macrophage-mediated antibody-dependent phagocytosis of tumor cells in vitro and improved responses to rituximab in the Raji human tumor xenograft mouse model. Combined with PD-1/PD-L1 blockade, AB21 improved response rates by facilitating monocyte activation, dendritic cell activation, and T cell effector functions resulting in long term, durable antitumor immunity. In cynomolgus monkeys, hAB21 has a half-life of 5.3 days at 10 mg/kg and complete target occupancy with no hematological toxicity or adverse findings at doses up to 30 mg/kg. Conclusions The in vitro and in vivo antitumor activity of hAB21 broadly recapitulates that of CD47 targeted therapies despite differences in ligand expression, binding partners, and function, validating the CD47–SIRPα axis as a fundamental myeloid checkpoint pathway and its blockade as promising therapeutic intervention for treatment of human malignancies.

Image-guided radiovirotherapy for multiple myeloma using a recombinant measles virus expressing the thyroidal sodium iodide symporter

Blood ◽  
2004 ◽  
Vol 103 (5) ◽  
pp. 1641-1646 ◽  
Author(s):  
David Dingli ◽  
Kah-Whye Peng ◽  
Mary E. Harvey ◽  
Philip R. Greipp ◽  
Michael K. O'Connor ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Tumor Cells ◽  
Measles Virus ◽  
Human Tumor ◽  
Tumor Xenograft ◽  
Human Tumor Xenograft ◽  
Sodium Iodide Symporter ◽  
Human Tumor Cells ◽  
Image Guided

AbstractThe Edmonston vaccine strain of measles virus (MV-Edm) propagates efficiently in a broad range of human tumor cells, killing them selectively. However, the oncolytic potency of MV-Edm in different human tumor xenograft therapy models is highly variable and there is no convenient way to map the distribution of virus-infected tissues in vivo. To enhance the oncolytic potency of MV-Edm against radiosensitive malignancies and to facilitate noninvasive imaging of infected tissues, we generated a recombinant MV-Edm encoding the human thyroidal iodide symporter (NIS). MV-NIS replicated almost as efficiently as unmodified MV-Edm, and human tumor cells efficiently concentrated radioiodine when infected with MV-NIS. Intratumoral spread of MV-NIS was noninvasively demonstrated by serial gamma-camera imaging of iodine-123 (123I) uptake both in MV-sensitive KAS-6/1 myeloma xenografts, which regressed completely after a single intravenous dose of MV-NIS, and in MM1 myeloma xenografts, which were unresponsive to MVNIS therapy. However, MV-resistant MM1 tumors regressed completely when 131I was administered 9 days after a single intravenous injection of MV-NIS (radiovirotherapy). 131I alone had no effect on MM1 tumor growth. While the potential hematopoietic toxicity of this new therapy requires further evaluation, image-guided radiovirotherapy is a promising new approach to the treatment of multiple myeloma, an incurable but highly radiosensitive plasma cell malignancy. Testing in other radiosensitive cancers is warranted.

scholarly journals 5,7-Dihydroxyflavone Enhances the Apoptosis-Inducing Potential of TRAIL in Human Tumor Cells via Regulation of Apoptosis-Related Proteins

2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Zhenzhen Zhang ◽  
Tingmei Ye ◽  
Xueting Cai ◽  
Jie Yang ◽  
Wuguang Lu ◽  
...  
Keyword(s):  
Hepg2 Cells ◽  
Combined Treatment ◽  
Xenograft Model ◽  
Human Tumor ◽  
Tumor Burden ◽  
Tumor Xenograft ◽  
Apoptotic Protein ◽  
Dietary Flavonoid ◽  
Induced Apoptosis

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising candidate for the treatment of cancer, because it preferentially induces apoptosis in numerous cancer cells with little or no effect on normal cells. 5,7-Dihydroxyflavone is a dietary flavonoid commonly found in many plants. Here we show that the combined treatment with 5,7-dihydroxyflavone and TRAIL at subtoxic concentrations induced strong apoptotic response in human hepatocarcinoma HepG2 cells, acute leukemia Jurkat T cells, and cervical carcinoma HeLa cells. We further investigated the mechanisms by which 5,7-dihydroxyflavone augments TRAIL-induced apoptosis in HepG2 cells. 5,7-Dihydroxyflavone up-regulated the expression of pro-apoptotic protein Bax, attenuated the expression of anti-apoptotic proteins Bcl-2, Mcl-1, and IAPs, and reduced the phosphorylation levels of Akt and STAT3, weakening the anti-apoptotic signals thus facilitating the process of apoptosis. Moreover, 5,7-dihydroxyflavone and TRAIL were well tolerated in mice, and the combination of 5,7-dihydroxyflavone and TRAIL reduced tumor burdenin vivoin a HepG2 tumor xenograft model. Interestingly, 5,7-dihydroxyflavone-mediated sensitization to TRAIL-induced cell death was not observed in normal human hepatocytes L-O2. These results suggest that the 5,7-dihydroxyflavone in combination with TRAIL might be used for cancer prevention and/or therapy.

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