The Experts below are selected from a list of 18177 Experts worldwide ranked by ideXlab platform
Win Ping Deng - One of the best experts on this subject based on the ideXlab platform.
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molecular imaging with 123i fiau 18f fudr 18f fet and 18f fdg for monitoring herpes simplex virus type 1 thymidine kinase and ganciclovir prodrug activation Gene therapy of cancer
The Journal of Nuclear Medicine, 2006Co-Authors: Hsinell Wang, Ren Shyan Liu, Mai Lin, Juri G Gelovani, Jengjong Hwang, Hong Jian Wei, Win Ping DengAbstract:The ability to monitor tumor responses during prodrug activation Gene therapy and other Anticancer Gene therapies is critical for their translation into clinical practice. Previously, we demonstrated the feasibility of noninvasive in vivo imaging with 131 I-5-iodo-2'-fluoro-1-β-D-arabinofuranosyluracil ( 131 I-FIAU) for monitoring herpes simplex virus type 1 thymidine kinase (HSV1-tk) cancer Gene expression in an experimental animal model. Here we tested the efficacy of SPECT with 123 I-FIAU and PET with 5- 18 F-fluoro-2'-deoxyuridine ( 18 F-FUdR), 2- 18 F-fluoroethyl-L-tyrosine ( 18 F-FET), and 18 F-FDG for monitoring tumor responses during prodrug activation Gene therapy with HSV1-tk and ganciclovir (GCV). Methods: In the flanks of FVB/N female mice, 4 tumors per animal were established by subcutaneous injection of 1×10 5 cells of NG4TL4 sarcoma cells, HSV1-tk-transduced NG4TL4-STK cells, or a mixture of these cells in different proportions to model different efficacies of transfection and HSV1-tk Gene expression levels in tumors. Ten days later, the animals were treated with GCV (10 mg/kg/d intraperitoneally) for 7 d. γ-Imaging with 123 I-FIAU and PET with 18 F-FUdR, 18 F-FET, and 18 F-FDG were performed before and after initiation of therapy with GCV in the same animal. Results: Before GCV treatment, no significant difference in weight and size was found in tumors that expressed different HSV1-tk levels, suggesting similar in vivo proliferation rates for NG4TL4 and NG4TL4-STK sarcomas. The accumulation of 123 I-FIAU at 24 h after injection was directly proportional to the percentage of NG4TL4-STK cells in the tumors. The 123 I-FIAU accumulation at 4 and 7 d of GCV therapy decreased significantly compared with pretreatment levels and was proportional to the percentage of HSV1-tk-positive tumor cells. Tumor uptake of 18 F-FUdR in all HSV1-tk-expressing tumors also decreased significantly compared with pretreatment levels and was proportional to the percentage of HSV1-tk-positive tumor cells. The accumulation of 18 F-FET decreased minimally (about 1.5-fold) and 18 F-FDG decreased only 2-fold after 7 d of GCV therapy, and the degree of reduction was proportional to the percentage of HSV1-tk-positive tumor cells. Conclusion: We have shown that γ-camera imaging with 123 I-FIAU was the most reliable method for prediction of tumor response to GCV therapy, which was proportional to the magnitude of HSV1-tk expression in tumor tissue. 123 I-FIAU imaging can be used to verify the efficacy of elimination of HSV1-tk-expressing cells by therapy with GCV. PET with 18 F-FUdR reliably visualizes proliferating tumor tissue and is most suitable for the assessment of responses in tumors undergoing HSV1-tk plus GCV prodrug activation Gene therapy. PET with 18 F-FDG or 18 F-FET can be used as additional "surrogate" biomarkers of the treatment response, although these radiotracers are less sensitive than 18 F-FUdR for monitoring tumor responses to prodrug activation Gene therapy with HSV1-tk and GCV in this sarcoma model.
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mesenchymal stem cell targeting of microscopic tumors and tumor stroma development monitored by noninvasive in vivo positron emission tomography imaging
Clinical Cancer Research, 2005Co-Authors: Shihchieh Hung, Win Ping Deng, Wenkuang Yang, Ren Shyan Liu, Chien Chih Lee, Rue Jen Lin, Den Mei Yang, Chi Wei ChangAbstract:The aim of this study was to assess the efficacy human mesenchymal stem cells (hMSC) for targeting microscopic tumors and suicide Gene or cytokine Gene therapy. Immunodeficient mice were transplanted s.c. with human colon cancer cells of HT-29 Inv2 or CCS line, and 3 to 4 days later, i.v. with "tracer" hMSCs expressing herpes simplex virus type 1 thymidine kinase (HSV1-TK) and enhanced green fluorescent protein (EGFP) reporter Genes. Subsequently, these tumors were examined for specificity and magnitude of HSV1-TK(+), EGFP(+) stem cell engraftment and proliferation in tumor stroma by in vivo positron emission tomography (PET) with (18)F-labeled 9-(4-fluoro-3-hydroxymethylbutyl)-guanine ([(18)F]-FHBG). In vivo PET images of tumors growing for 4 weeks showed the presence of HSV1-TK(+) tumor stroma with an average of 0.36 +/- 0.24% ID/g [(18)F]-FHBG accumulation. In vivo imaging results were validated by in situ correlative histochemical, immunofluorescent, and cytometric analyses, which revealed EGFP expression in vWF(+) and CD31(+) endothelial cells of capillaries and larger blood vessels, in germinal layer of dermis and hair follicles proximal to the s.c. tumor site. These differentiated HSV1-TK(+), GFP(+) endothelial cells had limited proliferative capacity and a short life span of <2 weeks in tumor fragments transplanted into secondary hosts. We conclude that hMSCs can target microscopic tumors, subsequently proliferate and differentiate, and contribute to formation of a significant portion of tumor stroma. PET imaging should facilitate clinical translation of stem cell-based Anticancer Gene therapeutic approaches by providing the means for in vivo noninvasive whole-body monitoring of trafficking, tumor targeting, and proliferation of HSV1-tk-expressing "tracer" hMSCs in tumor stroma.
Shu Wang - One of the best experts on this subject based on the ideXlab platform.
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targeted suicide Gene therapy for glioma using human embryonic stem cell derived neural stem cells Genetically modified by baculoviral vectors
Gene Therapy, 2012Co-Authors: Ying Zhao, Dang Hoang Lam, Jing Yang, J Lin, Chenkhong Tham, Shu WangAbstract:Tumor-tropic neural stem cells (NSCs) can be used in the Trojan horse approach as cellular vehicles for targeted delivery of therapeutic agents to distant tumor sites. To realize this cancer therapy potential, it is important to have a renewable source to Generate large quantities of uniform human NSCs. Here, we reported that NSCs derived from HES1 human embryonic stem cell line were capable of migrating into intracranial glioma xenografts after systemic injection or after intracranial injection at a site distant from the tumor. To test whether the HES1-derived NSCs can be used for cancer Gene therapy, we used a baculoviral vector to introduce the herpes simplex virus thymidine kinase suicide Gene into the cells and demonstrated that baculovirus-mediated transGene expression may last for at least 3 weeks in NSCs. After being injected into the cerebral hemisphere opposite the tumor site and in the presence of ganciclovir, NSCs expressing the suicide Gene were able to inhibit the growth of human glioma xenografts and prolong survival of tumor-bearing mice. Our findings suggest that human embryonic stem cells could potentially serve as a clinically viable source for production of cellular vehicles suitable for targeted Anticancer Gene therapy.
Garth L Warnock - One of the best experts on this subject based on the ideXlab platform.
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cancer cell oriented migration of mesenchymal stem cells engineered with an Anticancer Gene pten an imaging demonstration
OncoTargets and Therapy, 2014Co-Authors: Zhuoshun Yang, Xuyong Sun, Longjun Dai, Xiangjun Tang, Xingrong Guo, Dandan Zou, Jingbo Feng, Jie Luo, Garth L WarnockAbstract:Background Mesenchymal stem cells (MSCs) have been considered to hold great potential as ideal carriers for the delivery of Anticancer agents since the discovery of their tumor tropism. This study was performed to demonstrate the effects of phosphatase and tensin homolog (PTEN) engineering on MSCs' capacity for cancer cell-oriented migration. Methods MSCs were engineered with a PTEN-bearing plasmid and the expression was confirmed with Western blotting. A human glioma cell line (DBTRG) was used as the target cell; DBTRG cell-oriented migration of MSCs was monitored with a micro speed photographic system. Results The expression of transfected PTEN in MSCs was identified by immunoblotting analysis and confirmed with cell viability assessment of target cells. The DBTRG cell-oriented migration of PTEN-engineered MSCs was demonstrated by a real-time dynamic monitoring system, and a phagocytosis-like action of MSCs was also observed. Conclusion MSCs maintained their capacity for cancer cell-directed migration after they were engineered with Anticancer Genes. This study provides the first direct evidence of MSCs' tropism post-Anticancer Gene engineering.
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Anticancer Gene engineered msc mediated cancer cell death an imaging demonstration
Engineering, 2012Co-Authors: Xuyong Sun, Zhuang Chen, Mani Roshan Moniri, Longjun Dai, Garth L WarnockAbstract:This study was performed to demonstrate the transportation of an engineered MSC-produced intracellular Anticancer Gene product between mesenchymal stem cell (MSC) and cancer cells. MSC-mediated Anticancer strategy has held great promise owing to MSCs’ capacity of tumor-directed migration and the availability of specific Anticancer Genes. All Anticancer Genes that have been used in previous MSC-mediated Anticancer studies were limited in functioning via extracellular mechanisms, mainly because of the restriction by cell membrane to macromolecules including proteins. In order to apply the majority of potent Anticancer Genes to the MSC-mediated Anticancer system, a specifically designed expression vector which bears an intracellular Anticancer Gene, PTEN, is utilized to demonstrate the feasibility of the system in cancer therapies. A transacting activator of transcription (TAT) was introduced into an expression vector followed by a segment for PTEN-RFP fusion protein. A direct demonstration of PTEN-RFP transportation between MSC and cancer cells was obtained from direct co-cultures. A marked cancer cell death was observed in indirect co-cultures with conditioned media from PTEN-transfected MSCs. The demonstration of PTEN-engineered MSC-produced PTEN transportation indicates the feasibility of applying intracellular Anticancer Gene expression system in MSC-mediated strategies for cancer therapy.
Ren Shyan Liu - One of the best experts on this subject based on the ideXlab platform.
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molecular imaging with 123i fiau 18f fudr 18f fet and 18f fdg for monitoring herpes simplex virus type 1 thymidine kinase and ganciclovir prodrug activation Gene therapy of cancer
The Journal of Nuclear Medicine, 2006Co-Authors: Hsinell Wang, Ren Shyan Liu, Mai Lin, Juri G Gelovani, Jengjong Hwang, Hong Jian Wei, Win Ping DengAbstract:The ability to monitor tumor responses during prodrug activation Gene therapy and other Anticancer Gene therapies is critical for their translation into clinical practice. Previously, we demonstrated the feasibility of noninvasive in vivo imaging with 131 I-5-iodo-2'-fluoro-1-β-D-arabinofuranosyluracil ( 131 I-FIAU) for monitoring herpes simplex virus type 1 thymidine kinase (HSV1-tk) cancer Gene expression in an experimental animal model. Here we tested the efficacy of SPECT with 123 I-FIAU and PET with 5- 18 F-fluoro-2'-deoxyuridine ( 18 F-FUdR), 2- 18 F-fluoroethyl-L-tyrosine ( 18 F-FET), and 18 F-FDG for monitoring tumor responses during prodrug activation Gene therapy with HSV1-tk and ganciclovir (GCV). Methods: In the flanks of FVB/N female mice, 4 tumors per animal were established by subcutaneous injection of 1×10 5 cells of NG4TL4 sarcoma cells, HSV1-tk-transduced NG4TL4-STK cells, or a mixture of these cells in different proportions to model different efficacies of transfection and HSV1-tk Gene expression levels in tumors. Ten days later, the animals were treated with GCV (10 mg/kg/d intraperitoneally) for 7 d. γ-Imaging with 123 I-FIAU and PET with 18 F-FUdR, 18 F-FET, and 18 F-FDG were performed before and after initiation of therapy with GCV in the same animal. Results: Before GCV treatment, no significant difference in weight and size was found in tumors that expressed different HSV1-tk levels, suggesting similar in vivo proliferation rates for NG4TL4 and NG4TL4-STK sarcomas. The accumulation of 123 I-FIAU at 24 h after injection was directly proportional to the percentage of NG4TL4-STK cells in the tumors. The 123 I-FIAU accumulation at 4 and 7 d of GCV therapy decreased significantly compared with pretreatment levels and was proportional to the percentage of HSV1-tk-positive tumor cells. Tumor uptake of 18 F-FUdR in all HSV1-tk-expressing tumors also decreased significantly compared with pretreatment levels and was proportional to the percentage of HSV1-tk-positive tumor cells. The accumulation of 18 F-FET decreased minimally (about 1.5-fold) and 18 F-FDG decreased only 2-fold after 7 d of GCV therapy, and the degree of reduction was proportional to the percentage of HSV1-tk-positive tumor cells. Conclusion: We have shown that γ-camera imaging with 123 I-FIAU was the most reliable method for prediction of tumor response to GCV therapy, which was proportional to the magnitude of HSV1-tk expression in tumor tissue. 123 I-FIAU imaging can be used to verify the efficacy of elimination of HSV1-tk-expressing cells by therapy with GCV. PET with 18 F-FUdR reliably visualizes proliferating tumor tissue and is most suitable for the assessment of responses in tumors undergoing HSV1-tk plus GCV prodrug activation Gene therapy. PET with 18 F-FDG or 18 F-FET can be used as additional "surrogate" biomarkers of the treatment response, although these radiotracers are less sensitive than 18 F-FUdR for monitoring tumor responses to prodrug activation Gene therapy with HSV1-tk and GCV in this sarcoma model.
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mesenchymal stem cell targeting of microscopic tumors and tumor stroma development monitored by noninvasive in vivo positron emission tomography imaging
Clinical Cancer Research, 2005Co-Authors: Shihchieh Hung, Win Ping Deng, Wenkuang Yang, Ren Shyan Liu, Chien Chih Lee, Rue Jen Lin, Den Mei Yang, Chi Wei ChangAbstract:The aim of this study was to assess the efficacy human mesenchymal stem cells (hMSC) for targeting microscopic tumors and suicide Gene or cytokine Gene therapy. Immunodeficient mice were transplanted s.c. with human colon cancer cells of HT-29 Inv2 or CCS line, and 3 to 4 days later, i.v. with "tracer" hMSCs expressing herpes simplex virus type 1 thymidine kinase (HSV1-TK) and enhanced green fluorescent protein (EGFP) reporter Genes. Subsequently, these tumors were examined for specificity and magnitude of HSV1-TK(+), EGFP(+) stem cell engraftment and proliferation in tumor stroma by in vivo positron emission tomography (PET) with (18)F-labeled 9-(4-fluoro-3-hydroxymethylbutyl)-guanine ([(18)F]-FHBG). In vivo PET images of tumors growing for 4 weeks showed the presence of HSV1-TK(+) tumor stroma with an average of 0.36 +/- 0.24% ID/g [(18)F]-FHBG accumulation. In vivo imaging results were validated by in situ correlative histochemical, immunofluorescent, and cytometric analyses, which revealed EGFP expression in vWF(+) and CD31(+) endothelial cells of capillaries and larger blood vessels, in germinal layer of dermis and hair follicles proximal to the s.c. tumor site. These differentiated HSV1-TK(+), GFP(+) endothelial cells had limited proliferative capacity and a short life span of <2 weeks in tumor fragments transplanted into secondary hosts. We conclude that hMSCs can target microscopic tumors, subsequently proliferate and differentiate, and contribute to formation of a significant portion of tumor stroma. PET imaging should facilitate clinical translation of stem cell-based Anticancer Gene therapeutic approaches by providing the means for in vivo noninvasive whole-body monitoring of trafficking, tumor targeting, and proliferation of HSV1-tk-expressing "tracer" hMSCs in tumor stroma.
Chi Wei Chang - One of the best experts on this subject based on the ideXlab platform.
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mesenchymal stem cell targeting of microscopic tumors and tumor stroma development monitored by noninvasive in vivo positron emission tomography imaging
Clinical Cancer Research, 2005Co-Authors: Shihchieh Hung, Win Ping Deng, Wenkuang Yang, Ren Shyan Liu, Chien Chih Lee, Rue Jen Lin, Den Mei Yang, Chi Wei ChangAbstract:The aim of this study was to assess the efficacy human mesenchymal stem cells (hMSC) for targeting microscopic tumors and suicide Gene or cytokine Gene therapy. Immunodeficient mice were transplanted s.c. with human colon cancer cells of HT-29 Inv2 or CCS line, and 3 to 4 days later, i.v. with "tracer" hMSCs expressing herpes simplex virus type 1 thymidine kinase (HSV1-TK) and enhanced green fluorescent protein (EGFP) reporter Genes. Subsequently, these tumors were examined for specificity and magnitude of HSV1-TK(+), EGFP(+) stem cell engraftment and proliferation in tumor stroma by in vivo positron emission tomography (PET) with (18)F-labeled 9-(4-fluoro-3-hydroxymethylbutyl)-guanine ([(18)F]-FHBG). In vivo PET images of tumors growing for 4 weeks showed the presence of HSV1-TK(+) tumor stroma with an average of 0.36 +/- 0.24% ID/g [(18)F]-FHBG accumulation. In vivo imaging results were validated by in situ correlative histochemical, immunofluorescent, and cytometric analyses, which revealed EGFP expression in vWF(+) and CD31(+) endothelial cells of capillaries and larger blood vessels, in germinal layer of dermis and hair follicles proximal to the s.c. tumor site. These differentiated HSV1-TK(+), GFP(+) endothelial cells had limited proliferative capacity and a short life span of <2 weeks in tumor fragments transplanted into secondary hosts. We conclude that hMSCs can target microscopic tumors, subsequently proliferate and differentiate, and contribute to formation of a significant portion of tumor stroma. PET imaging should facilitate clinical translation of stem cell-based Anticancer Gene therapeutic approaches by providing the means for in vivo noninvasive whole-body monitoring of trafficking, tumor targeting, and proliferation of HSV1-tk-expressing "tracer" hMSCs in tumor stroma.