13 results on '"Wang, Rong-Fu"'
Search Results
2. DHX29 functions as a RNA co-sensor for MDA5-mediated EMCV-specific antiviral immunity.
- Author
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Zhu, Qingyuan, Tan, Peng, Li, Yinyin, Lin, Meng, Li, Chaoran, Mao, Jingrong, Cui, Jun, Zhao, Wei, Wang, Helen Y., and Wang, Rong-Fu
- Subjects
MELANOMA ,MELANOMA treatment ,CELL differentiation ,ENCEPHALOMYOCARDITIS virus ,CARRIER proteins ,PICORNAVIRUSES ,GENETICS - Abstract
Melanoma differentiation-associated gene-5 (MDA5) recognizes distinct subsets of viruses including Encephalomyocarditis virus (EMCV) of picornavirus family, but the molecular mechanisms underlying the specificity of the viral recognition of MDA5 in immune cells remain obscure. DHX29 is a RNA helicase required for the translation of 5’ structured mRNA of host and many picornaviruses (such as EMCV). We identify that DXH29 as a key RNA co-sensor, plays a significant role for specific recognition and triggering anti-EMCV immunity. We have observed that DHX29 regulates MDA5-, but not RIG-I-, mediated type I interferon signaling by preferentially interacting with structured RNAs and specifically with MDA5 for enhancing MDA5-dsRNA binding affinity. Overall, our results identify a critical role for DHX29 in innate immune response and provide molecular insights into the mechanisms by which DHX29 recognizes 5’ structured EMCV RNA and interacts with MDA5 for potent type I interferon signaling and antiviral immunity. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
3. Identification of DRG-1 As a Melanoma-Associated Antigen Recognized by CD4+ Th1 Cells.
- Author
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Kiniwa, Yukiko, Li, Jiang, Wang, Mingjun, Sun, Chuang, Lee, Jeffrey E., Wang, Rong-Fu, and Wang, Helen Y.
- Subjects
CD4 antigen ,T helper cells ,IMMUNOTHERAPY ,MELANOMA treatment ,ANTINEOPLASTIC agents - Abstract
Immunotherapy has emerged as a promising strategy for the treatment of metastatic melanoma. Clinical studies have demonstrated the feasibility of cancer immunotherapy using tumor antigens recognized by CD8
+ T cells. However, the overall immune responses induced by these antigens are too weak and transient to induce tumor regression in the majority of patients who received immunization. A growing body of evidence suggests that CD4+ T helper (Th) cells play an important role in antitumor immunity. Therefore, the identification of MHC class II-restricted tumor antigens capable of stimulating CD4+ T cells may provide opportunities for developing effective cancer vaccines. To this end, we describe the identification of developmentally regulated GTP-binding protein 1 (DRG-1) as a melanoma-associated antigen recognized by HLA-DR11-restricted CD4+ Th1 cells. Epitope mapping analysis showed that the DRG1248-268 epitope of DRG-1 was required for T cell recognition. Reverse transcription-polymerase chain reaction revealed that DRG-1 was highly expressed in melanoma cell lines but not in normal tissues. DRG-1 knockdown by lentiviral-based shRNA suppressed melanoma cell proliferation and soft agar colony formation. Taken together, these data suggest that DRG-1 plays an important role in melanoma cell growth and transformation, indicating that DRG1 may represent a novel target for CD4+ T cell-mediated immunotherapy in melanoma. [ABSTRACT FROM AUTHOR]- Published
- 2015
- Full Text
- View/download PDF
4. Stage-Dependent and Locus-Specific Role of Histone Demethylase Jumonji D3 (JMJD3) in the Embryonic Stages of Lung Development.
- Author
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Li, Qingtian, Wang, Helen Y., Chepelev, Iouri, Zhu, Qingyuan, Wei, Gang, Zhao, Keji, and Wang, Rong-Fu
- Subjects
BASIC proteins ,HISTONE demethylases ,GENE expression ,EMBRYOLOGY ,LUNG development - Abstract
Histone demethylases have emerged as important players in developmental processes. Jumonji domain containing-3 (Jmjd3) has been identified as a key histone demethylase that plays a critical role in the regulation of gene expression; however, the in vivo function of Jmjd3 in embryonic development remains largely unknown. To this end, we generated Jmjd3 global and conditional knockout mice. Global deletion of Jmjd3 induces perinatal lethality associated with defective lung development. Tissue and stage-specific deletion revealed that Jmjd3 is dispensable in the later stage of embryonic lung development. Jmjd3 ablation downregulates the expression of genes critical for lung development and function, including AQP-5 and SP-B. Jmjd3-mediated alterations in gene expression are associated with locus-specific changes in the methylation status of H3K27 and H3K4. Furthermore, Jmjd3 is recruited to the SP-B promoter through interactions with the transcription factor Nkx2.1 and the epigenetic protein Brg1. Taken together, these findings demonstrate that Jmjd3 plays a stage-dependent and locus-specific role in the mouse lung development. Our study provides molecular insights into the mechanisms by which Jmjd3 regulates target gene expression in the embryonic stages of lung development. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
5. An Experimental Study on 131I-CHIBA-1001: A Radioligand for α7 Nicotinic Acetylcholine Receptors.
- Author
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Yin, Lei, Zhao, Qian, Li, Ling, Zhang, Su Lei, Chen, Xue Qi, Ma, Chao, Kang, Lei, Liu, Meng, Zhang, Chun Li, Yan, Ping, and Wang, Rong Fu
- Subjects
CHOLINERGIC receptors ,RADIOLIGAND assay ,PATHOLOGICAL physiology ,NEUROPSYCHIATRY ,POSITRON emission tomography ,ALZHEIMER'S disease ,RADIOLABELING ,BRAIN imaging - Abstract
Objective: The α7 nicotinic acetylcholine receptors (nAChRs) play a vital role in the pathophysiology of neuropsychiatric diseases such as Alzheimer’s disease and depression. However, there is currently no suitable positron emission tomography (PET) or Single-Photon Emission Computed Tomography (SPECT) radioligands for imaging α7 nAChRs in brain. Here our aim is to radiosynthesize a novel SPECT radioligand
131 I-CHIBA-1001 for whole body biodistribution study and in vivo imaging of α7 nAChRs in brain. Method:131 I-CHIBA-1001 was radiosynthesized by chloramine-T method. Different conditions of reaction time and temperature were tested to get a better radiolabeling yield. Radiolabeling yield and radiochemical purities of131 I-CHIBA-1001 were analyzed by thin layer chromatography (TLC) and high-performance liquid chromatography (HPLC) system. Whole body biodistribution study was performed at different time points post injection of131 I-CHIBA-1001 in KM mice. Monkey subject was used for in vivo SPECT imaging in brain. Result: The radiolabeling yield of131 I-CHIBA-1001 reached 96% within 1.5∼2.0 h at 90∼95°C. The radiochemical purity reached more than 99% after HPLC purification.131 I-CHIBA-1001 was highly stable in saline and fresh human serum in room temperature and 37°C separately. The biodistribution data of brain at 15, 30, and 60 min were 11.05±1.04%ID/g, 8.8±0.04%ID/g and 6.28±1.13%ID/g, respectively. In experimental SPECT imaging, the distribution of radioactivity in the brain regions was paralleled with the distribution of α7 nAChRs in the monkey brain. Moreover, in the blocking SPECT imaging study, the selective α7 nAChR agonist SSR180711 blocked the radioactive uptake in the brain successfully. Conclusion: The CHIBA-1001 can be successfully radiolabeled with131 I using the chloramine-T method.131 I-CHIBA-1001 can successfully accumulate in the monkey brain and image the α7 acetylcholine receptors.131 I-CHIBA-1001 can be a candidate for imagingα7 acetylcholine receptors, which will be of great value for the diagnosis and treatment of mental diseases. [ABSTRACT FROM AUTHOR]- Published
- 2013
- Full Text
- View/download PDF
6. A Novel 99mTc-Labeled Molecular Probe for Tumor Angiogenesis Imaging in Hepatoma Xenografts Model: A Pilot Study.
- Author
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Zhao, Qian, Yan, Ping, Wang, Rong Fu, Zhang, Chun Li, Li, Ling, and Yin, Lei
- Subjects
NEOVASCULARIZATION inhibitors ,MOLECULAR probes ,HEPATOCELLULAR carcinoma ,XENOGRAFTS ,PILOT projects ,LABORATORY mice ,NUCLEAR medicine ,RADIONUCLIDE imaging - Abstract
Introduction: Visualization of tumor angiogenesis using radionuclide targeting provides important diagnostic information. In previous study, we proved that an arginine-arginine-leucine (RRL) peptide should be a tumor endothelial cell specific binding sequence. The overall aim of this study was to evaluate whether
99m Tc-radiolabeled RRL could be noninvasively used for imaging of malignant tumors in vivo, and act as a new molecular probe targeting tumor angiogenesis. Methods: The RRL peptide was designed and radiosynthesized with99m Tc by a one-step method. The radiolabeling efficiency and radiochemical purity were then characterized in vitro.99m Tc-RRL was injected intravenously in HepG2 xenograft-bearing BALB/c nude mice. Biodistribution and in vivo imaging were performed periodically. The relationship between tumor size and %ID uptake of99m Tc-RRL was also explored. Results: The labeling efficiencies of99m Tc-RRL reached 76.9%±4.5% (n = 6) within 30–60 min at room temperature, and the radiochemical purity exceeded 96% after purification. In vitro stability experiment revealed the radiolabeled peptide was stable. Biodistribution data showed that99m Tc-RRL rapidly cleared from the blood and predominantly accumulated in the kidneys and tumor. The specific uptake of99m Tc-RRL in tumor was significantly higher than that of unlabeled RRL blocking and free pertechnetate control test after injection (p<0.05). The ratio of the tumor-to-muscle exceeded 6.5, tumor-to-liver reached 1.98 and tumor-to-blood reached 1.95. In planar gamma imaging study, the tumors were imaged clearly at 2–6 h after injection of99m Tc-RRL, whereas the tumor was not imaged clearly in blocking group. The tumor-to-muscle ratio of images with99m Tc-RRL was comparable with that of18 F-FDG PET images. Immunohistochemical analysis verified the excessive vasculature of tumor. There was a linear relationship between the tumor size and uptake of99m Tc-RRL with R2 = 0.821. Conclusion:99m Tc-RRL can be used as a potential candidate for visualization of tumor angiogenesis in malignant carcinomas. [ABSTRACT FROM AUTHOR]- Published
- 2013
- Full Text
- View/download PDF
7. Identification of Special AT-Rich Sequence Binding Protein 1 as a Novel Tumor Antigen Recognized by CD8+ T Cells: Implication for Cancer Immunotherapy.
- Author
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Wang, Mingjun, Yin, Bingnan, Matsueda, Satoko, Deng, Lijuan, Li, Ying, Zhao, Wei, Zou, Jia, Li, Qingtian, Loo, Christopher, Wang, Rong-Fu, and Wang, Helen Y.
- Subjects
CARRIER proteins ,TUMOR antigens ,T cells ,CANCER immunotherapy ,GENE expression ,PHENOTYPES ,CANCER vaccines - Abstract
Background: A large number of human tumor-associated antigens that are recognized by CD8
+ T cells in a human leukocyte antigen class I (HLA-I)-restricted fashion have been identified. Special AT-rich sequence binding protein 1 (SATB1) is highly expressed in many types of human cancers as part of their neoplastic phenotype, and up-regulation of SATB1 expression is essential for tumor survival and metastasis, thus this protein may serve as a rational target for cancer vaccines. Methodology/Principal Findings: Twelve SATB1-derived peptides were predicted by an immuno-informatics approach based on the HLA-A*02 binding motif. These peptides were examined for their ability to induce peptide-specific T cell responses in peripheral blood mononuclear cells (PBMCs) obtained from HLA-A*02+ healthy donors and/or HLA-A*02+ cancer patients. The recognition of HLA-A*02+ SATB1-expressing cancer cells was also tested. Among the twelve SATB1-derived peptides, SATB1565–574 frequently induced peptide-specific T cell responses in PBMCs from both healthy donors and cancer patients. Importantly, SATB1565–574 -specific T cells recognized and killed HLA-A*02+ SATB1+ cancer cells in an HLA-I-restricted manner. Conclusions/Significance: We have identified a novel HLA-A*02-restricted SATB1-derived peptide epitope recognized by CD8+ T cells, which, in turn, recognizes and kills HLA-A*02+ SATB1+ tumor cells. The SATB1-derived epitope identified may be used as a diagnostic marker as well as an immune target for development of cancer vaccines. [ABSTRACT FROM AUTHOR]- Published
- 2013
- Full Text
- View/download PDF
8. Identification of Prostate-Specific G-Protein Coupled Receptor as a Tumor Antigen Recognized by CD8+ T Cells for Cancer Immunotherapy.
- Author
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Matsueda, Satoko, Wang, Mingjun, Weng, Jinsheng, Ying Li, Yin, Bingnan, Zou, Jia, Qingtian Li, Zhao, Wei, Peng, Weiyi, Legras, Xavier, Loo, Christopher, Wang, Rong.-Fu, Wang, Helen Y., and Hoque, Mohammad O.
- Subjects
PROSTATE cancer ,PROSTATE-specific antigen ,G protein coupled receptors ,T cells ,PEPTIDES ,HISTOCOMPATIBILITY antigens ,CANCER vaccines - Abstract
Background: Prostate cancer is the most common cancer among elderly men in the US, and immunotherapy has been shown to be a promising strategy to treat patients with metastatic castration-resistant prostate cancer. Efforts to identify novel prostate specific tumor antigens will facilitate the development of effective cancer vaccines against prostate cancer. Prostate-specific G-protein coupled receptor (PSGR) is a novel antigen that has been shown to be specifically over-expressed in human prostate cancer tissues. In this study, we describe the identification of PSGR-derived peptide epitopes recognized by CD8
+ T cells in an HLA-A2 dependent manner. Methodology/Principal Findings: Twenty-one PSGR-derived peptides were predicted by an immuno-informatics approach based on the HLA-A2+ binding motif. These peptides were examined for their ability to induce peptide-specific T cell responses in peripheral blood mononuclear cells (PBMCs) obtained from either HLA-A2+ healthy donors or HLA- A2+ prostate cancer patients. The recognition of HLA-A2 positive and PSGR expressing LNCaP cells was also tested. Among the 21 PSGR-derived peptides, three peptides, PSGR3, PSGR4 and PSGR14 frequently induced peptide-specific T cell responses in PBMCs from both healthy donors and prostate cancer patients. Importantly, these peptide-specific T cells recognized and killed LNCaP prostate cancer cells in an HLA class I-restricted manner. Conclusions/Significance: We have identified three novel HLA-A2-restricted PSGR-derived peptides recognized by CD8+ T cells, which, in turn, recognize HLA-A2+ and PSGR+ tumor cells. The PSGR-derived peptides identified may be used as diagnostic markers as well as immune targets for development of anticancer vaccines. [ABSTRACT FROM AUTHOR]- Published
- 2012
- Full Text
- View/download PDF
9. Identification of DRG-1 As a Melanoma-Associated Antigen Recognized by CD4+ Th1 Cells.
- Author
-
Kiniwa Y, Li J, Wang M, Sun C, Lee JE, Wang RF, and Wang HY
- Subjects
- Cell Line, Tumor, Cell Proliferation genetics, Epitope Mapping, GTP-Binding Proteins genetics, HLA-DR Serological Subtypes immunology, Humans, RNA Interference, RNA, Small Interfering genetics, Antigens, Neoplasm immunology, Epitopes, T-Lymphocyte immunology, GTP-Binding Proteins immunology, Melanoma immunology, Th1 Cells immunology
- Abstract
Immunotherapy has emerged as a promising strategy for the treatment of metastatic melanoma. Clinical studies have demonstrated the feasibility of cancer immunotherapy using tumor antigens recognized by CD8(+) T cells. However, the overall immune responses induced by these antigens are too weak and transient to induce tumor regression in the majority of patients who received immunization. A growing body of evidence suggests that CD4(+) T helper (Th) cells play an important role in antitumor immunity. Therefore, the identification of MHC class II-restricted tumor antigens capable of stimulating CD4(+) T cells may provide opportunities for developing effective cancer vaccines. To this end, we describe the identification of developmentally regulated GTP-binding protein 1 (DRG-1) as a melanoma-associated antigen recognized by HLA-DR11-restricted CD4(+) Th1 cells. Epitope mapping analysis showed that the DRG1248-268 epitope of DRG-1 was required for T cell recognition. Reverse transcription-polymerase chain reaction revealed that DRG-1 was highly expressed in melanoma cell lines but not in normal tissues. DRG-1 knockdown by lentiviral-based shRNA suppressed melanoma cell proliferation and soft agar colony formation. Taken together, these data suggest that DRG-1 plays an important role in melanoma cell growth and transformation, indicating that DRG1 may represent a novel target for CD4(+) T cell-mediated immunotherapy in melanoma.
- Published
- 2015
- Full Text
- View/download PDF
10. An experimental study on (131)I-CHIBA-1001: a radioligand for α7 nicotinic acetylcholine receptors.
- Author
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Yin L, Zhao Q, Li L, Zhang SL, Chen XQ, Ma C, Kang L, Liu M, Zhang CL, Yan P, and Wang RF
- Subjects
- Animals, Brain diagnostic imaging, Brain metabolism, Haplorhini, Humans, Ligands, Male, Mice, Positron-Emission Tomography, Protein Binding, Rats, Tissue Distribution, Tomography, Emission-Computed, Single-Photon, Bridged Bicyclo Compounds, Heterocyclic chemistry, Bridged Bicyclo Compounds, Heterocyclic metabolism, Iodine Radioisotopes chemistry, alpha7 Nicotinic Acetylcholine Receptor metabolism
- Abstract
Objective: The α7 nicotinic acetylcholine receptors (nAChRs) play a vital role in the pathophysiology of neuropsychiatric diseases such as Alzheimer's disease and depression. However, there is currently no suitable positron emission tomography (PET) or Single-Photon Emission Computed Tomography (SPECT) radioligands for imaging α7 nAChRs in brain. Here our aim is to radiosynthesize a novel SPECT radioligand (131)I-CHIBA-1001 for whole body biodistribution study and in vivo imaging of α7 nAChRs in brain., Method: (131)I-CHIBA-1001 was radiosynthesized by chloramine-T method. Different conditions of reaction time and temperature were tested to get a better radiolabeling yield. Radiolabeling yield and radiochemical purities of (131)I-CHIBA-1001 were analyzed by thin layer chromatography (TLC) and high-performance liquid chromatography (HPLC) system. Whole body biodistribution study was performed at different time points post injection of (131)I-CHIBA-1001 in KM mice. Monkey subject was used for in vivo SPECT imaging in brain., Result: The radiolabeling yield of (131)I-CHIBA-1001 reached 96% within 1.5∼2.0 h at 90∼95°C. The radiochemical purity reached more than 99% after HPLC purification. (131)I-CHIBA-1001 was highly stable in saline and fresh human serum in room temperature and 37°C separately. The biodistribution data of brain at 15, 30, and 60 min were 11.05±1.04%ID/g, 8.8±0.04%ID/g and 6.28±1.13%ID/g, respectively. In experimental SPECT imaging, the distribution of radioactivity in the brain regions was paralleled with the distribution of α7 nAChRs in the monkey brain. Moreover, in the blocking SPECT imaging study, the selective α7 nAChR agonist SSR180711 blocked the radioactive uptake in the brain successfully., Conclusion: The CHIBA-1001 can be successfully radiolabeled with (131)I using the chloramine-T method. (131)I-CHIBA-1001 can successfully accumulate in the monkey brain and image the α7 acetylcholine receptors. (131)I-CHIBA-1001 can be a candidate for imagingα7 acetylcholine receptors, which will be of great value for the diagnosis and treatment of mental diseases.
- Published
- 2013
- Full Text
- View/download PDF
11. Identification of special AT-rich sequence binding protein 1 as a novel tumor antigen recognized by CD8+ T cells: implication for cancer immunotherapy.
- Author
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Wang M, Yin B, Matsueda S, Deng L, Li Y, Zhao W, Zou J, Li Q, Loo C, Wang RF, and Wang HY
- Subjects
- Biomarkers, Tumor genetics, Biomarkers, Tumor immunology, CD8-Positive T-Lymphocytes immunology, Cancer Vaccines genetics, Cancer Vaccines immunology, Cell Line, Tumor, Epitopes genetics, Epitopes immunology, Gene Expression Regulation, Neoplastic immunology, Histocompatibility Antigens Class I genetics, Humans, Immunotherapy, Matrix Attachment Region Binding Proteins immunology, Neoplasms genetics, Peptides genetics, Peptides immunology, Antigens, Neoplasm genetics, Histocompatibility Antigens Class I immunology, Matrix Attachment Region Binding Proteins genetics, Neoplasms immunology, Neoplasms therapy
- Abstract
Background: A large number of human tumor-associated antigens that are recognized by CD8(+) T cells in a human leukocyte antigen class I (HLA-I)-restricted fashion have been identified. Special AT-rich sequence binding protein 1 (SATB1) is highly expressed in many types of human cancers as part of their neoplastic phenotype, and up-regulation of SATB1 expression is essential for tumor survival and metastasis, thus this protein may serve as a rational target for cancer vaccines., Methodology/principal Findings: Twelve SATB1-derived peptides were predicted by an immuno-informatics approach based on the HLA-A*02 binding motif. These peptides were examined for their ability to induce peptide-specific T cell responses in peripheral blood mononuclear cells (PBMCs) obtained from HLA-A*02(+) healthy donors and/or HLA-A*02(+) cancer patients. The recognition of HLA-A*02(+) SATB1-expressing cancer cells was also tested. Among the twelve SATB1-derived peptides, SATB1(565-574) frequently induced peptide-specific T cell responses in PBMCs from both healthy donors and cancer patients. Importantly, SATB1(565-574)-specific T cells recognized and killed HLA-A*02(+) SATB1(+) cancer cells in an HLA-I-restricted manner., Conclusions/significance: We have identified a novel HLA-A*02-restricted SATB1-derived peptide epitope recognized by CD8(+) T cells, which, in turn, recognizes and kills HLA-A*02(+) SATB1(+) tumor cells. The SATB1-derived epitope identified may be used as a diagnostic marker as well as an immune target for development of cancer vaccines.
- Published
- 2013
- Full Text
- View/download PDF
12. A novel 99mTc-labeled molecular probe for tumor angiogenesis imaging in hepatoma xenografts model: a pilot study.
- Author
-
Zhao Q, Yan P, Wang RF, Zhang CL, Li L, and Yin L
- Subjects
- Amino Acid Sequence, Animals, Carcinoma, Hepatocellular blood supply, Carcinoma, Hepatocellular pathology, Female, Hep G2 Cells, Humans, Liver Neoplasms, Experimental blood supply, Liver Neoplasms, Experimental pathology, Mice, Mice, Inbred BALB C, Mice, Nude, Neoplasm Transplantation, Pilot Projects, Radionuclide Imaging, Tissue Distribution, Tumor Burden, Carcinoma, Hepatocellular diagnostic imaging, Liver Neoplasms, Experimental diagnostic imaging, Neovascularization, Pathologic diagnostic imaging, Oligopeptides pharmacokinetics, Organotechnetium Compounds pharmacokinetics, Radiopharmaceuticals pharmacokinetics
- Abstract
Introduction: Visualization of tumor angiogenesis using radionuclide targeting provides important diagnostic information. In previous study, we proved that an arginine-arginine-leucine (RRL) peptide should be a tumor endothelial cell specific binding sequence. The overall aim of this study was to evaluate whether (99m)Tc-radiolabeled RRL could be noninvasively used for imaging of malignant tumors in vivo, and act as a new molecular probe targeting tumor angiogenesis., Methods: The RRL peptide was designed and radiosynthesized with (99m)Tc by a one-step method. The radiolabeling efficiency and radiochemical purity were then characterized in vitro. (99m)Tc-RRL was injected intravenously in HepG2 xenograft-bearing BALB/c nude mice. Biodistribution and in vivo imaging were performed periodically. The relationship between tumor size and %ID uptake of (99m)Tc-RRL was also explored., Results: The labeling efficiencies of (99m)Tc-RRL reached 76.9% ± 4.5% (n = 6) within 30-60 min at room temperature, and the radiochemical purity exceeded 96% after purification. In vitro stability experiment revealed the radiolabeled peptide was stable. Biodistribution data showed that (99m)Tc-RRL rapidly cleared from the blood and predominantly accumulated in the kidneys and tumor. The specific uptake of (99m)Tc-RRL in tumor was significantly higher than that of unlabeled RRL blocking and free pertechnetate control test after injection (p<0.05). The ratio of the tumor-to-muscle exceeded 6.5, tumor-to-liver reached 1.98 and tumor-to-blood reached 1.95. In planar gamma imaging study, the tumors were imaged clearly at 2-6 h after injection of (99m)Tc-RRL, whereas the tumor was not imaged clearly in blocking group. The tumor-to-muscle ratio of images with (99m)Tc-RRL was comparable with that of (18)F-FDG PET images. Immunohistochemical analysis verified the excessive vasculature of tumor. There was a linear relationship between the tumor size and uptake of (99m)Tc-RRL with R(2) = 0.821., Conclusion: (99m)Tc-RRL can be used as a potential candidate for visualization of tumor angiogenesis in malignant carcinomas.
- Published
- 2013
- Full Text
- View/download PDF
13. Identification of prostate-specific G-protein coupled receptor as a tumor antigen recognized by CD8(+) T cells for cancer immunotherapy.
- Author
-
Matsueda S, Wang M, Weng J, Li Y, Yin B, Zou J, Li Q, Zhao W, Peng W, Legras X, Loo C, Wang RF, and Wang HY
- Subjects
- Amino Acid Sequence, CD8-Positive T-Lymphocytes immunology, CD8-Positive T-Lymphocytes metabolism, Cancer Vaccines chemical synthesis, Cell Line, Tumor, HLA Antigens metabolism, Humans, Immunotherapy, Active, Interferon-gamma metabolism, Male, Neoplasm Proteins metabolism, Peptide Fragments chemical synthesis, Prostatic Neoplasms immunology, Prostatic Neoplasms therapy, Receptors, Odorant metabolism, T-Lymphocytes, Cytotoxic immunology, T-Lymphocytes, Cytotoxic metabolism, Antigens, Neoplasm immunology, Cancer Vaccines immunology, Neoplasm Proteins immunology, Peptide Fragments immunology, Prostatic Neoplasms metabolism, Receptors, Odorant immunology
- Abstract
Background: Prostate cancer is the most common cancer among elderly men in the US, and immunotherapy has been shown to be a promising strategy to treat patients with metastatic castration-resistant prostate cancer. Efforts to identify novel prostate specific tumor antigens will facilitate the development of effective cancer vaccines against prostate cancer. Prostate-specific G-protein coupled receptor (PSGR) is a novel antigen that has been shown to be specifically over-expressed in human prostate cancer tissues. In this study, we describe the identification of PSGR-derived peptide epitopes recognized by CD8(+) T cells in an HLA-A2 dependent manner., Methodology/principal Findings: Twenty-one PSGR-derived peptides were predicted by an immuno-informatics approach based on the HLA-A2 binding motif. These peptides were examined for their ability to induce peptide-specific T cell responses in peripheral blood mononuclear cells (PBMCs) obtained from either HLA-A2(+) healthy donors or HLA-A2(+) prostate cancer patients. The recognition of HLA-A2 positive and PSGR expressing LNCaP cells was also tested. Among the 21 PSGR-derived peptides, three peptides, PSGR3, PSGR4 and PSGR14 frequently induced peptide-specific T cell responses in PBMCs from both healthy donors and prostate cancer patients. Importantly, these peptide-specific T cells recognized and killed LNCaP prostate cancer cells in an HLA class I-restricted manner., Conclusions/significance: We have identified three novel HLA-A2-restricted PSGR-derived peptides recognized by CD8(+) T cells, which, in turn, recognize HLA-A2(+) and PSGR(+) tumor cells. The PSGR-derived peptides identified may be used as diagnostic markers as well as immune targets for development of anticancer vaccines.
- Published
- 2012
- Full Text
- View/download PDF
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