scholarly journals Epigallocatechin-3-gallate-induced vascular normalization in A549-cell xenograft-bearing nude mice: therapeutic efficacy in combination with chemotherapy

2019 ◽  
Vol Volume 11 ◽  
pp. 2425-2439 ◽  
Author(s):  
Pengbo Deng ◽  
ChengPing Hu ◽  
Zeng Xiong ◽  
Yuanyuan Li ◽  
Juan Jiang ◽  
...  
Keyword(s):  
Nude Mice ◽  
A549 Cell ◽  
Therapeutic Efficacy ◽  
Vascular Normalization

scholarly journals Repeated Intraperitoneal -Radioimmunotherapy of Ovarian Cancer in Mice

2010 ◽  
Vol 2010 ◽  
pp. 1-5 ◽  
Author(s):  
Jörgen Elgqvist ◽  
Håkan Andersson ◽  
Holger Jensen ◽  
Helena Kahu ◽  
Sture Lindegren ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Monoclonal Antibody ◽  
Cell Line ◽  
Nude Mice ◽  
Therapeutic Efficacy ◽  
Therapeutic Index ◽  
Repeated Treatment ◽  
Treatment Regimens ◽  
Potential Increase

The aim of this study was to investigate the therapeutic efficacy of -radioimmunotherapy of ovarian cancer in mice using different fractionated treatment regimens. The study was performed using the monoclonal antibody MX35 F labeled with the -particle emitter .Methods. Nude mice were intraperitoneally inoculated with ~ cells of the cell line NIH:OVCAR-3. Four weeks later 6 groups of animals were given F as a single or as a repeated treatment of up to 6 times ( in each group). The fractionated treatments were given every seventh day. Control animals were treated with unlabeled F (). Eight weeks posttreatment the animals were sacrificed and the presence of macro- and microscopic tumors and ascites was determined.Results. The tumor-free fractions (TFFs) of the animals, defined as the fraction of animals with no macro- and microtumors and no ascites, were 0.17, 0.11, 0.39, 0.44, 0.44, and 0.67 when treated with F once or 2, 3, 4, 5, or 6 times, respectively. Repeated treatment 3 times or more resulted in a significantly higher () TFF than compared to treatment once or twice. The presence of ascites decreased from 15 out of 18 animals in the group given only one treatment to zero for the 2 groups given 5 or 6 fractions. Treatment with unlabeled F resulted in a TFF of zero.Conclusion. Weekly repeated intraperitoneal injections of tolerable amounts of activity of F of up to 6 times produced increased therapeutic efficacy without observed toxicity, indicating a potential increase of the therapeutic index.

Influence of antibody protein dose on therapeutic efficacy of radioiodinated antibodies in nude mice bearing GW-39 human tumor

1992 ◽  
Vol 35 (2) ◽  
pp. 127-134 ◽  
Author(s):  
Otto C. Boerman ◽  
Robert M. Sharkey ◽  
George Y. Wong ◽  
Rosalyn D. Blumenthal ◽  
Rosarito L. Aninipot ◽  
...  
Keyword(s):  
Nude Mice ◽  
Therapeutic Efficacy ◽  
Human Tumor

Anti-CD38 Pretargeted Radioimmunotherapy Demonstrates Therapeutic Efficacy In a Human Multiple Myeloma Mouse Xenograft Model

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1842-1842
Author(s):  
Damian J. Green ◽  
Nural N. Orgun ◽  
Mark D. Hylarides ◽  
John M. Pagel ◽  
Donald K. Hamlin ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Plasma Cell ◽  
Nude Mice ◽  
Therapeutic Efficacy ◽  
Untreated Control ◽  
Novel Agents ◽  
Beta Particle ◽  
Control Groups ◽  
Myeloma Cells ◽  
Athymic Nude Mice

Abstract Abstract 1842 Multiple myeloma (MM) remains incurable despite improved response rates and improved progression free survival in the era of therapy with novel agents, including bortezomib, thalidomide, and lenalidomide. Disease persistence is presumably due to residual malignant plasma cell clones that evade or develop resistance to available therapies. The efficacy of radioimmunotherapy (RIT) in the treatment of hematologic malignancies is well established and the radiosensitivity of malignant plasma cells has been demonstrated in both preclinical and clinical settings. The ectoenzyme receptor CD38 is a plasma cell antigen that exhibits relatively specific, stable and uniform expression (95–100%) at a high epitope density on myeloma cells, making it an attractive target for antibody based therapies, including RIT. Pretargeted RIT (PRIT), using a multi-step streptavidin (SA)-biotin targeting system enhances the therapeutic index of delivered radiation. We have generated an anti-CD38 antibody (Ab)-SA synthetic chemical conjugate (OKT10-SA). The OKT10-SA construct binds with high avidity to myeloma cells while retaining full biotin-binding capability for radiolabeled DOTA-biotin. Blood, tumor and nonspecific organ uptakes of OKT10-SA were directly measured in biodistribution experiments involving athymic nude mice bearing human MM xenograft tumors. Groups of 5 mice with s.c. L363 human MM (IgG) xenograft tumors received 1.4 nmol (300 μg) of either OKT10-SA (anti-CD38 SA) or an IgG1 isotype matched control Ab BHV1-SA (bovine herpes virus-1) 22 hrs prior to synthetic biotin-acetyl-galactosamine clearing agent (CA; 5.8 nmol [50 μg]) and 24 hrs prior to trace labeled 111In-DOTA-biotin (1 μg). The CA removed >95% of both unbound OKT10-SA and BHV1-SA from the mouse circulation within 30 minutes of administration. Animals were euthanized and comprehensive tissue biodistributions were assessed 2, 24, 48 and 96 hrs after 111In-DOTA-biotin injection. Tumors excised from mice pretargeted with OKT10-SA contained 13.1 ± 1.9 % of the injected dose of 111In-DOTA-biotin per gram (% ID/g) after 2 hrs and 8.8 ± 2.8 % ID/g after 24 hrs compared to 2.4 ± 0.6 % ID/g after 2 hrs and 0.9 ± 0.4 % ID/g after 24 hrs in tumors excised from control mice pretargeted with BHV1-SA. Tumor-to-normal organ ratios of absorbed radioactivity were 8:1; 10:1; 8:1; and 6:1 respectively for blood, lung, liver and kidney in mice pretargeted with OKT10-SA; compared to 0.6:1; 0.9:1; 0.8:1 and 0.4:1 respectively, in control mice pretargeted with BHV1-SA. Therapy studies were then performed in athymic nude mice (n=9-10/group) bearing s.c. L363 human MM xenograft tumors. Reagent concentrations and time-points for administration of OKT10-SA, BHV1-SA and CA were identical to those reported for the biodistribution studies. The high energy beta particle emitter 90Yttrium (t1/2 = 64 hrs) was used as the therapeutic radionuclide. 90Y-DOTA-biotin (2 μg) was labeled with 400 μCi, 800 μCi, or 1200 μCi per mouse in 3 OKT10-SA groups and 3 control groups (untreated control; 800 μCi or 1200 μCi 90Y-DOTA-biotin following BHV1-SA). All mice in the untreated control and BHV1-SA control groups experienced exponential MM tumor growth and 78% of the untreated control animals required euthanasia within 17 days. All mice pretargeted with OKT10-SA demonstrated tumor shrinkage by day 6 at all dose levels (see figure). After 17 days, 90% of the OKT10-SA treated animals in the 400 μCi and 1200 μCi groups and 100% of the animals in the 800 μCi remained alive. One animal treated with 1200 μCi was euthanized on day 10 due to weight loss, however the remaining 9 animals from that group were 106 ±9% of initial body weight on day 17. Objective remissions were observed within 6 days in 100% of the mice treated with OKT10-SA followed by 1200 μCi of 90Y-DOTA-biotin, including 100% complete remissions (no detectable tumor in OKT10-SA treated mice compared to tumors that were 5240 ± 2495% of initial tumor volume in untreated control animals) by day 17. These studies represent the first application of both PRIT and CD38 targeted radioimmunotherapy in MM. Favorable OKT10-SA biodistribution findings correlate with early evidence of therapeutic efficacy. Tumor responses in this MM xenograft tumor model are encouraging, but long term toxicity and survival results are not yet mature. Future studies combining PRIT and novel agents are planned in xenograft and SCID-hu myeloma models. Disclosures: Gopal: Millenium. Wood:BD Biosciences: Research Funding.

Fractionated radioimmunotherapy of intraperitoneally growing ovarian cancer in nude mice with 211At-MX35 F(ab′)2: therapeutic efficacy and myelotoxicity

2006 ◽  
Vol 33 (8) ◽  
pp. 1065-1072 ◽  
Author(s):  
Jörgen Elgqvist ◽  
Håkan Andersson ◽  
Tom Bäck ◽  
Ingela Claesson ◽  
Ragnar Hultborn ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Nude Mice ◽  
Therapeutic Efficacy

scholarly journals In vivo and in vitro effects of hyperplasia suppressor gene on the proliferation and apoptosis of lung adenocarcinoma A549 cells

2018 ◽  
Vol 38 (5) ◽  
Author(s):  
Zhen-Qing Sun ◽  
Gang Chen ◽  
Qiang Guo ◽  
He-Fei Li ◽  
Zhou Wang
Keyword(s):  
Cell Proliferation ◽  
Lung Adenocarcinoma ◽  
Gene Silencing ◽  
Nude Mice ◽  
A549 Cell ◽  
A549 Cells ◽  
Suppressor Gene ◽  
Proliferation And Apoptosis ◽  
Lung Adenocarcinoma A549

Lung adenocarcinoma is the most common subtype of non-small cell lung cancer (NSCLC). Hyperplasia suppressor gene (HSG) has been reported to inhibit cell proliferation, migration, and remodeling in cardiovascular diseases. However, there lacks systematic researches on the effect of HSG on the apoptosis and proliferation of lung adenocarcinoma A549 cells and data of in vivo experiments. The present study aims to investigate the effects of HSG gene silencing on proliferation and apoptosis of lung adenocarcinoma A549 cells. The human lung adenocarcinoma A549 cell was selected to construct adenovirus vector. Reverse transcription-quantitative PCR (RT-qPCR) and Western blot analysis were conducted to detect expressions of HSG and apoptosis related-proteins. Cell Counting Kit (CCK)-8 assay was performed to assess A549 cell proliferation and flow cytometry to analyze cell cycle and apoptosis rate. The BALB/C nude mice were collected to establish xenograft model. Silenced HSG showed decreased mRNA and protein expressions of HSG, and elevated A549 cell survival rates at the time point of 24, 48, and 72 h. The ratio of cells at G0/G1 phase and apoptosis rate decreased and the ratio of cells at S- and G2/M phases increased following the silencing of HSG. There were decreases of B cell lymphoma-2 (Bcl-2)-associated X protein (Bax), Caspase-3, and Caspase-8 expressions but increases in Bcl-2 induced by silenced HSG. As for the xenograft in nude mice, tumor volume increased, and apoptosis index (AI) decreased after HSG silencing. These results indicate that HSG gene silencing may promote the proliferation of A549 cells and inhibit the apoptosis. HSG may be a promising target for the treatment of lung adenocarcinoma.

Retroviral Vector-Producing Mesenchymal Stem Cells for Tumor Tracking and Therapeutic Gene Amplification in Suicide Cancer Gene Therapy.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1917-1917
Author(s):  
Ryosuke Uchibori ◽  
Takashi Okada ◽  
Takayuki Ito ◽  
Masashi Urabe ◽  
Hiroaki Mizukami ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Nude Mice ◽  
Therapeutic Efficacy ◽  
Transgene Expression ◽  
Glioma Cells ◽  
Retroviral Vector ◽  
Cancer Gene Therapy ◽  
Cancer Gene ◽  
Tumor Bearing ◽  
Anti Cancer

Abstract Mesenchymal stem cells (MSCs) are known to have a tendency to accumulate at the site of tumors, and therefore can be utilized as a platform for targeted delivery of anti-cancer agents. The MSC-based targeted cancer gene therapy can enhance the therapeutic efficacy, because MSCs are considered to reach tumors including metastatic lesions and to deliver therapeutic molecules in a concentrated fashion. This targeted therapy can also reduce systemic adverse side effects, because the anti-cancer agents act locally at the site of tumors without elevating their systemic concentrations. In the present study, we developed genetically-modified MSCs that produce retroviral vectors encoding HSVtk, aiming at augmenting therapeutic efficacy of systemic suicide cancer gene therapy. The tumor tropism and anti-tumor effects of vector-producing MSCs (VP-MSCs) were examined by intravascular injection in tumor-bearing nude mice. MSCs isolated from the bone marrow of SD rats were transfected with plasmid DNA expressing luciferase alone (=non-VP-MSCs) or whole retroviral vector components (LTR-Luc or LTR-HSVtk with Gag-pol and VSV-G) (=VP-MSCs) by nucleofection. To assess tumor tropism of MSCs, nude mice were subcutaneously inoculated with 9L rat glioma cells or Rat-1 fibroblasts, and were subsequently injected with luciferase-expressing MSCs through the left ventricular cavity. The transgene expression was periodically traced by using an in vivo imaging system. As a result, the transgene expression accumulated at the site of subcutaneous 9L tumors, but undetectable at the site of Rat-1 fibroblasts. In addition, the injection of luciferase-expressing VP-MSCs caused much stronger signal of bioluminescence at the site of 9L tumors compared with luciferease-expressing non-VP-MSCs. Immunostaining study showed that luciferase-positive cells (injected MSCs and transduced glioma cells) were detected at the periphery of tumors. To evaluate the therapeutic efficacy, tumor-bearing nude mice were treated with non-VP-MSCs or VP-MSCs combined with HSVtk/GCV system and then the size of subcutaneous tumors was periodically measured. In this model experiments, tumor growth was more efficiently suppressed by injecting VP-MSCs compared with non-VP-MSCs. The present study suggests the effectiveness of VP-MSCs in suicide cancer gene therapy. The therapeutic benefit of this strategy should be further examined in orthotopic and metastatic tumor models.

Therapeutic Efficacy of Astatine-211–Labeled Trastuzumab on Radioresistant SKOV-3 Tumors in Nude Mice

2007 ◽  
Vol 69 (2) ◽  
pp. 572-579 ◽  
Author(s):  
Stig Palm ◽  
Tom Bäck ◽  
Ingela Claesson ◽  
Anna Danielsson ◽  
Jörgen Elgqvist ◽  
...  
Keyword(s):  
Nude Mice ◽  
Therapeutic Efficacy
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