scholarly journals Targeting the Vasculature of Colorectal Carcinoma with a Fused Protein of(RGD)3-tTF

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Zheng-jie Huang ◽  
Yilin Zhao ◽  
Wei-yuan Luo ◽  
Jun You ◽  
Shui-wen Li ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Survival Time ◽  
Tumor Necrosis ◽  
Protein Targeting ◽  
Clotting Time ◽  
Coagulation Activity ◽  
Promising Strategy ◽  
Volume Blood ◽  
Vessel Thrombosis

Purpose. Truncated tissue factor (tTF) fusion protein targeting tumor vasculature can induce tumor vascular thrombosis and necrosis. Here, we generated (RGD)3-tTF in which three arginine-glycine-aspartic (RGD) targeting integrinαvβ3and tTF induce blood coagulation in tumor vessels.Methods. The bioactivities of (RGD)3-tTF including coagulation activity,FXactivation, and binding with integrinαvβ3were performed. The fluorescent labeled (RGD)3-tTF was intravenously injected into tumor-bearing mice and traced in vivo. The tumor growth, volume, blood vessel thrombosis, tumor necrosis, and survival time of mice treated with (RGD)3-tTF were evaluated.Results. The clotting time andFXactivation of (RGD)3-tTF were similar to that of TF (P>0.05) but different with that of RGD (P<0.05). (RGD)3-tTF presented a higher binding withαvβ3than that of RGD and TF at the concentration of 0.2 μmol/L (P<0.05). (RGD)3-tTF could specifically assemble in tumor and be effective in reducing tumor growth by selectively inducing tumor blood vessels thrombosis and tumor necrosis which were absent in mice treated with RGD or TF. The survival time of mice treated with (RGD)3-tTF was higher than that of mice treated with TF or RGD (P<0.05).Conclusion. (RGD)3-tTF may be a promising strategy for the treatment of colorectal cancer.

scholarly journals Promising potential of [177Lu]Lu-DOTA-folate to enhance tumor response to immunotherapy—a preclinical study using a syngeneic breast cancer model

2020 ◽  
Author(s):  
Patrycja Guzik ◽  
Klaudia Siwowska ◽  
Hsin-Yu Fang ◽  
Susan Cohrs ◽  
Peter Bernhardt ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Survival Time ◽  
Tumor Cells ◽  
Median Survival ◽  
Breast Tumor ◽  
Median Survival Time ◽  
Therapy Outcome ◽  
Minor Effect

Abstract Purpose It was previously demonstrated that radiation effects can enhance the therapy outcome of immune checkpoint inhibitors. In this study, a syngeneic breast tumor mouse model was used to investigate the effect of [177Lu]Lu-DOTA-folate as an immune stimulus to enhance anti-CTLA-4 immunotherapy. Methods In vitro and in vivo studies were performed to characterize NF9006 breast tumor cells with regard to folate receptor (FR) expression and the possibility of tumor targeting using [177Lu]Lu-DOTA-folate. A preclinical therapy study was performed over 70 days with NF9006 tumor-bearing mice that received vehicle only (group A); [177Lu]Lu-DOTA-folate (5 MBq; 3.5 Gy absorbed tumor dose; group B); anti-CTLA-4 antibody (3 × 200 μg; group C), or both agents (group D). The mice were monitored regarding tumor growth over time and signs indicating adverse events of the treatment. Results [177Lu]Lu-DOTA-folate bound specifically to NF9006 tumor cells and tissue in vitro and accumulated in NF9006 tumors in vivo. The treatment with [177Lu]Lu-DOTA-folate or an anti-CTLA-4 antibody had only a minor effect on NF9006 tumor growth and did not substantially increase the median survival time of mice (23 day and 19 days, respectively) as compared with untreated controls (12 days). [177Lu]Lu-DOTA-folate sensitized, however, the tumors to anti-CTLA-4 immunotherapy, which became obvious by reduced tumor growth and, hence, a significantly improved median survival time of mice (> 70 days). No obvious signs of adverse effects were observed in treated mice as compared with untreated controls. Conclusion Application of [177Lu]Lu-DOTA-folate had a positive effect on the therapy outcome of anti-CTLA-4 immunotherapy. The results of this study may open new perspectives for future clinical translation of folate radioconjugates.

Growth-related changes of phosphorus metabolites in VX-2 carcinoma implanted into rabbit thigh muscle: in vivo 31P MR spectroscopy

2016 ◽  
Author(s):  
Hyeong-Kil Kim ◽  
Gwang Woo Jeong ◽  
Tae-Hoon Kim ◽  
Gwang-Won Kim ◽  
Jong-Bong Kim
Keyword(s):  
Tumor Growth ◽  
Intracellular Ph ◽  
Tumor Necrosis ◽  
Time Course ◽  
Ph Value ◽  
Thigh Muscle ◽  
Ph Values ◽  
Concentration Changes ◽  
Phosphorus Metabolites

The purpose of this study was to evaluate the usefulness of in vivo 31P magnetic resonance spectroscopy (MRS) for monitoring changes in growth-related phosphate metabolite concentration and intracellular pH value in rabbit thigh muscle implanted with VX-2 carcinoma. The time-course magnetic resonance imaging (MRI) and in vivo 31P MRS were examined weekly in the course of 10 weeks following the onset of a VX-2 carcinoma implantation. The spectra were quantitatively analyzed to obtain vital information on the time course variation of the phosphorus metabolites and intracellular pH value according to the tumor growth. Elevation in the concentrations of phosphormonoesters (PME), inorganic phosphate (Pi), and phosphodiesters (PDE) was observed over the time course of 3-4 weeks after the implantation of VX2 carcinoma, while the rest of the metabolites, PCr and ATP tended to be constant. The concentration changes of PME, Pi, and PDE were positively correlated with the volumes of tumor necrosis. The intracellular pH values decreased with the time course of tumor growth and the volumes of tumor necrosis. In vivo 31P MRS is capable of non-invasive monitoring of intracellular pH values as well as the concentration changes of phosphate metabolites during tumor growth.

scholarly journals Antitumor effect ofBothrops jararacavenom

2002 ◽  
Vol 11 (2) ◽  
pp. 99-104 ◽  
Author(s):  
Reinaldo J. da Silva ◽  
Márcia G. da Silva ◽  
Lízia C. Vilela ◽  
Denise Fecchio
Keyword(s):  
Tumor Growth ◽  
Survival Time ◽  
Antitumor Effect ◽  
Mononuclear Cells ◽  
Experimental Studies ◽  
Tumor Growth Inhibition ◽  
Peritoneal Cells ◽  
Eat Cells

Many experimental studies have been carried out using snake venoms for the treatment of animal tumors, with controversial results. While some authors have reported an antitumor effect of treatment with specific snake venom fractions, others have reported no effects after this treatment. The aim of this study was to evaluate the effect ofBothrops jararacavenom (BjV) on Ehrlich ascites tumor (EAT) cellsin vivoandin vitro. In thein vivostudy, Swiss mice were inoculated with EAT cells by the intraperitoneal (i.p.) route and treated withBjV venom (0.4 mg/kg, i.p.), on the 1st, 4th, 7th, 10th, and 13th days. Mice were evaluated for total and differential cells number on the 2nd, 5th, 8th, 11th and 14th days. The survival time was also evaluated after 60 days of tumor growth. In thein vitrostudy, EAT and normal peritoneal cells were cultivated in the presence of differentBjV concentrations (2.5, 5.0, 10.0, 20.0, 40.0, and 80 μg) and viability was verified after 3, 6, 12 and 24 h of cultivation. Results were analyzed statistically by the Kruskal-Wallis and Tukey tests at the 5% level of significance. It was observed thatin vivotreatment withBjV induced tumor growth inhibition, increased animal survival time, decreased mortality, increased the influx of polymorphonuclear leukocytes on the early stages of tumor growth, and did not affect the mononuclear cells number.In vitrotreatment withBjV produced a dose-dependent toxic effect on EAT and peritoneal cells, with higher effects against peritoneal cells. Taken together, our results demonstrate thatBjV has an important antitumor effect. This is the first report showing thisin vivoeffect for this venom.

scholarly journals BRD7 Promotes Cell Proliferation and Tumor Growth Through Stabilization of c-Myc in Colorectal Cancer

2021 ◽  
Vol 9 ◽  
Author(s):  
Ran Zhao ◽  
Yukun Liu ◽  
Chunchun Wu ◽  
Mengna Li ◽  
Yanmei Wei ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Tumor Growth ◽  
Cell Cycle Progression ◽  
Protein Targeting ◽  
Clinical Stage ◽  
Ubiquitin Proteasome

BRD7 functions as a crucial tumor suppressor in numerous malignancies. However, the effects of BRD7 on colorectal cancer (CRC) progression are still unknown. Here, based on the BRD7 knockout (BRD7–/–) and BRD7flox/flox (BRD7+/+) mouse models constructed in our previous work, we established an azoxymethane/dextran sodium sulfate (AOM/DSS)-induced mouse model. BRD7+/+ mice were found to be highly susceptible to AOM/DSS-induced colitis-associated CRC, and BRD7 significantly promoted cell proliferation and cell cycle G1/S transition but showed no significant effect on cell apoptosis. Furthermore, BRD7 interacted with c-Myc and stabilized c-Myc by inhibiting its ubiquitin–proteasome-dependent degradation. Moreover, restoring the expression of c-Myc in BRD7-silenced CRC cells restored cell proliferation, cell cycle progression, and tumor growth in vitro and in vivo. In addition, BRD7 and c-Myc were both significantly upregulated in CRC patients, and high expression of these proteins was associated with clinical stage and poor prognosis in CRC patients. Collectively, BRD7 functions as an oncogene and promotes CRC progression by regulating the ubiquitin–proteasome-dependent stabilization of c-Myc protein. Targeting the BRD7/c-Myc axis could be a potential therapeutic strategy for CRC.

scholarly journals GBP5 drives malignancy of glioblastoma via the Src/ERK1/2/MMP3 pathway

2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Xiaoting Yu ◽  
Jing Jin ◽  
Yanwen Zheng ◽  
Hua Zhu ◽  
Hui Xu ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Rna Interference ◽  
Tumor Growth ◽  
Survival Time ◽  
Primary Brain Tumor ◽  
Migration And Invasion ◽  
Clinical Samples ◽  
Novel Target

AbstractGuanylate binding proteins (GBPs), a family of interferon-inducible large GTPase, play a pivotal role in cell-autonomous immunity and tumor malignant transformation. Glioblastoma (GBM) is the most prevalent and lethal primary brain tumor in adults. Here we show that GBP5 was highly expressed in GBM cell lines and in clinical samples, especially in the mesenchymal subtype. The expression levels of GBP5 were negatively correlated with the prognosis of GBM patients. Overexpression of GBP5 promoted the proliferation, migration, and invasion of GBM cells in vitro and in vivo. In contrast, silencing GBP5 by RNA interference exhibited the opposite effects. Consequently, targeting GBP5 in GBM cells resulted in impaired tumor growth and prolonged survival time of mice with GBM tumors. We further identified that the Src/ERK1/2/MMP3 axis was essential for GBP5-promoted GBM aggressiveness. These findings suggest that GBP5 may represent a novel target for GBM intervention.

scholarly journals Protective and Antitumor Effects of Oxidal and Pyrucet in Hamsters with Experimental Graffi Tumor

2021 ◽  
pp. 1-19
Author(s):  
Reneta Toshkova ◽  
Ignat Ignatov ◽  
Georgi Gluhchev ◽  
Georgi Dinkov
Keyword(s):  
Tumor Growth ◽  
Protective Effect ◽  
Survival Time ◽  
Tumor Cells ◽  
Favorable Effect ◽  
Experimental Therapy ◽  
Antitumor Effects ◽  
Combination Drug ◽  
Tumor Bearing

The use of combination drug therapy instead of monotherapy is a new positive and promising approach in the treatment of cancer. Oxidal® and Pyrucet® are food supplements containing Methylene blue (USP), Caffeine (USP), Salicylic acid (USP) and Ethyl Acetoacetate and Ethyl Pyruvate respectively. The therapeutic significance of each of these compounds (their derivatives) is well established, but no data are available on their combined action in in vivo experimental tumor models. The aim of the present study was to investigate the in vivo protective effect of mono- and combined experimental therapy with dietary supplements Oxidal® and Pyrucet® in the Graffi myeloid tumor model in hamsters. For this purpose, the two drugs were administered alone or in combination in two treatment regimens - prophylactic (before) and therapeutic (simultaneously) with the transplantation of Graffi tumor cells. The protective effect was determined by the biometric parameters of tumor growth (transplantability, tumor size, mortality, mean survival time, survival rate) recorded during the experiment. The results showed a favorable effect of both drugs, administered alone or in combination, before and simultaneously with the transplantation of tumor cells on the appearance and development of Graffi tumor in hamsters. About 2-fold lower transplantability, prolongation of the latency period by 7 days, inhibition of tumor growth till 30thday of experiments, reduced mortality and increased individual and overall survival time between 7 to 10 days were observed in the Graffi tumor-bearing hamsters with experimental therapy compared to control-Graffi tumor-bearing hamsters, without therapy. The obtained data revealed that Oxidal® and Pyrucet® could be a promising candidate for the treatment of tumor diseases.

CSIG-03. GBP5 DRIVES MALIGNANCY OF GLIOBLASTOMA

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi33-vi33
Author(s):  
Ming Li ◽  
Clark Chen
Keyword(s):  
Brain Tumor ◽  
Rna Interference ◽  
Tumor Growth ◽  
Survival Time ◽  
Primary Brain Tumor ◽  
Migration And Invasion ◽  
Clinical Samples ◽  
Novel Target

Abstract Guanylate binding proteins (GBPs), a family of interferon-inducible large GTPase, play a pivotal role in cell-autonomous immunity and tumor malignant transformation. Glioblastoma (GBM) is the most prevalent and lethal primary brain tumor in adults. Here we show that GBP5 was highly expressed in GBM cell lines and in clinical samples, especially in the mesenchymal subtype. The expression levels of GBP5 were negatively correlated with the prognosis of GBM patients. Overexpression of GBP5 promoted the proliferation, migration, and invasion of GBM cells in vitro and in vivo. In contrast, silencing GBP5 by RNA interference exhibited the opposite effects. Consequently, targeting GBP5 in GBM cells resulted in impaired tumor growth and prolonged survival time of mice with GBM tumors. We further identified that the Src/ERK1/2/MMP3 axis was essential for GBP5-promoted GBM aggressiveness. These findings suggest that GBP5 may represent a novel target for GBM intervention.

Evaluation of antitumor effect of tumor necrosis factor in terms of protein metabolism and cell cycle kinetics

1993 ◽  
Vol 265 (2) ◽  
pp. C365-C374 ◽  
Author(s):  
J. M. Wan ◽  
F. Fogt ◽  
B. R. Bistrian ◽  
N. W. Istfan
Keyword(s):  
Cell Cycle ◽  
Tumor Necrosis Factor ◽  
Tumor Growth ◽  
Protein Metabolism ◽  
Tumor Necrosis ◽  
Compensatory Mechanism ◽  
Protein Breakdown ◽  
Cell Cycle Kinetics ◽  
Necrosis Factor

To determine the significance of protein breakdown in regulating tumor growth and to better understand the antitumor mechanism of tumor necrosis factor in vivo, we measured the effects of a 6-h constant intravenous infusion of human recombinant tumor necrosis factor-alpha (rHuTNF) on tumor protein metabolism and cell cycle kinetics in rats bearing the Walker-256 carcinosarcoma. Protein metabolism was investigated with the use of [14C]leucine infusion; estimates of tumor cell cycle kinetics were obtained in vivo by use of 5-bromo-2'-deoxyuridine (BrdUrd) pulse labeling and bivariate BrdUrd/DNA analysis by flow cytometry. Reduction in tumor growth by rHuTNF was associated with a dose-dependent increase in tumor proteolysis but no change in tumor protein synthesis. At the cellular level, rHuTNF had a significant cytostatic effect on G2/M cells and caused a marked decrease in the fraction of cells capable of BrdUrd uptake. Release of BrdUrd, an indicator of cell death, was noted in only 7.5% of tumor cells labeled at the beginning of rHuTNF infusion. These results suggest that either tumor protein breakdown may influence cell cycle activity by regulating cytoplasmic protein mass or that tumor proteolysis may be a compensatory mechanism for limiting cytoplasmic size when cellular division is interrupted suddenly.

Fluorinated dendrimer for TRAIL gene therapy in cancer treatment

2016 ◽  
Vol 4 (7) ◽  
pp. 1354-1360 ◽  
Author(s):  
Yitong Wang ◽  
Mingming Wang ◽  
Hui Chen ◽  
Hongmei Liu ◽  
Qiang Zhang ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Tumor Necrosis Factor ◽  
Tumor Growth ◽  
Cancer Treatment ◽  
Cancer Cells ◽  
Tumor Necrosis ◽  
Highly Efficient ◽  
Necrosis Factor

The transfection of tumor necrosis factor-related apoptosis-inducing ligand gene by using fluorinated dendrimer is highly efficient and low toxic, resulting in efficient killing of cancer cells in vitro and suppressing tumor growth in vivo.

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