19 results on '"Zibo Li"'
Search Results
2. Supplementary Tables 1 - 2 from Monoclonal Antibody against Cell Surface GRP78 as a Novel Agent in Suppressing PI3K/AKT Signaling, Tumor Growth, and Metastasis
- Author
-
Parkash S. Gill, Amy S. Lee, Zibo Li, Peter S. Conti, Stan Louie, Genyuan Zhu, Dan Li, Shuanglong Liu, Dezheng Dong, Valery Krasnoperov, Satyajit K. Mitra, Shiuan Wey, Yue Zhou, Wenming Gao, Xiuqing Li, and Ren Liu
- Abstract
PDF file - 62K, Table S1. Humanized MAb159 Pharmacokinetics in mouse. Table S2. Toxicology study of humanized MAb159 in mouse.
- Published
- 2023
3. Supplementary Figures 1 - 9 from Monoclonal Antibody against Cell Surface GRP78 as a Novel Agent in Suppressing PI3K/AKT Signaling, Tumor Growth, and Metastasis
- Author
-
Parkash S. Gill, Amy S. Lee, Zibo Li, Peter S. Conti, Stan Louie, Genyuan Zhu, Dan Li, Shuanglong Liu, Dezheng Dong, Valery Krasnoperov, Satyajit K. Mitra, Shiuan Wey, Yue Zhou, Wenming Gao, Xiuqing Li, and Ren Liu
- Abstract
PDF file - 736K, Fig. S1. Generation and characterization of MAb159. Fig. S2. MAb159 induces GRP78 endocytosis through clathrin mediated pathway. Fig. S3. MAb159 induces apoptosis of tumor cells in vitro. Fig. S4. Surface GRP78 Forms Complex with PI3K. Fig. S5. Surface GRP78 level in cancer cell lines. Fig. S6. MAb159 treatment of xenograft tumor leads to reduced vessel density and mTOR signaling. Fig. S7. MAb159 shows no toxicity to normal organs in tumor xenograft study. Fig. S8. Inhibition of primary tumor growth and metastasis by MAb159 in 4T1 orthotopic model. Fig. S9. MAb159 inhibits the growth of hormone refractory mouse prostate cancer cell CE1 in vivo.
- Published
- 2023
4. Data from Integrin-targeted imaging and therapy with RGD4C-TNF fusion protein
- Author
-
Xiaoyuan Chen, Amir Kashefi, Lina He, Zibo Li, Weibo Cai, Kai Chen, and Hui Wang
- Abstract
This study used integrin αvβ3 as a target for tumor-specific delivery of tumor necrosis factor-α (TNF). The fusion protein RGD4C-TNF bound specifically to αvβ3 as evidenced by cell receptor binding assay and noninvasive micro-positron emission tomography imaging. 64Cu-DOTA-RGD4C-TNF had significantly higher activity accumulation in integrin-positive tumors (U87MG and MDA-MB-435) but not in integrin-negative tumors (C6) compared with 64Cu-DOTA-TNF. The magnitude of tumor uptake of 64Cu-DOTA-RGD4C-TNF correlated well with the αvβ3 level (U87MG > MDA-MB-435 > C6). Tumor accumulation of 64Cu-DOTA-RGD4C-TNF could be effectively blocked by c(RGDyK) peptide in αvβ3-positive tumor models, suggesting αvβ3 specificity of RGD4C-TNF fusion protein in vivo. Furthermore, although the fusion of RGD4C moiety to TNF had little effect on the bioactivity and cytotoxicity of RGD4C-TNF compared with TNF in cell culture, RGD4C-TNF was significantly more potent than TNF in inhibiting orthotopic MDA-MB-435 tumor growth. Ex vivo tissue staining confirmed specific cytotoxicity of RGD4C-TNF against integrin-positive tumor cells and tumor vasculature. [Mol Cancer Ther 2008;7(5):1044–53]
- Published
- 2023
5. Supplementary Figure from Integrin-targeted imaging and therapy with RGD4C-TNF fusion protein
- Author
-
Xiaoyuan Chen, Amir Kashefi, Lina He, Zibo Li, Weibo Cai, Kai Chen, and Hui Wang
- Abstract
Supplementary Figure from Integrin-targeted imaging and therapy with RGD4C-TNF fusion protein
- Published
- 2023
6. Data from Monoclonal Antibody against Cell Surface GRP78 as a Novel Agent in Suppressing PI3K/AKT Signaling, Tumor Growth, and Metastasis
- Author
-
Parkash S. Gill, Amy S. Lee, Zibo Li, Peter S. Conti, Stan Louie, Genyuan Zhu, Dan Li, Shuanglong Liu, Dezheng Dong, Valery Krasnoperov, Satyajit K. Mitra, Shiuan Wey, Yue Zhou, Wenming Gao, Xiuqing Li, and Ren Liu
- Abstract
Purpose: The ER chaperone GRP78 translocates to the surface of tumor cells and promotes survival, metastasis, and resistance to therapy. An oncogenic function of cell surface GRP78 has been attributed to the activation of the phosphoinositide 3-kinase (PI3K) pathway. We intend to use a novel anti-GRP78 monoclonal antibody (MAb159) to attenuate PI3K signaling and inhibit tumor growth and metastasis.Experimental Design: MAb159 was characterized biochemically. Antitumor activity was tested in cancer cell culture, tumor xenograft models, tumor metastasis models, and spontaneous tumor models. Cancer cells and tumor tissues were analyzed for PI3K activity. MAb159 was humanized and validated for diagnostic and therapeutic application.Results: MAb159 specifically recognized surface GRP78, triggered GRP78 endocytosis, and localized to tumors but not to normal organs in vivo. MAb159 inhibited tumor cell proliferation and enhanced tumor cell death both in vitro and in vivo. In MAb159-treated tumors, PI3K signaling was inhibited without compensatory MAPK pathway activation. Furthermore, MAb159 halted or reversed tumor progression in the spontaneous PTEN–loss-driven prostate and leukemia tumor models, and inhibited tumor growth and metastasis in xenograft models. Humanized MAb159, which retains high affinity, tumor specific localization, and the antitumor activity, was nontoxic in mice, and had desirable pharmacokinetics.Conclusions: GRP78-specific antibody MAb159 modulates the PI3K pathway and inhibits tumor growth and metastasis. Humanized MAb159 will enter human trials shortly. Clin Cancer Res; 19(24); 6802–11. ©2013 AACR.
- Published
- 2023
7. Supplementary Figure 1 from Noninvasive De novo Imaging of Human Embryonic Stem Cell–Derived Teratoma Formation
- Author
-
Joseph C. Wu, Xiaoyuan Chen, Weibo Cai, Hui Wang, Kai Chen, Zhaofei Liu, Andrew Lee, Zibo Li, and Feng Cao
- Abstract
Supplementary Figure 1 from Noninvasive De novo Imaging of Human Embryonic Stem Cell–Derived Teratoma Formation
- Published
- 2023
8. Supplementary Methods and Figure Legend from Noninvasive De novo Imaging of Human Embryonic Stem Cell–Derived Teratoma Formation
- Author
-
Joseph C. Wu, Xiaoyuan Chen, Weibo Cai, Hui Wang, Kai Chen, Zhaofei Liu, Andrew Lee, Zibo Li, and Feng Cao
- Abstract
Supplementary Methods and Figure Legend from Noninvasive De novo Imaging of Human Embryonic Stem Cell–Derived Teratoma Formation
- Published
- 2023
9. Data from Noninvasive De novo Imaging of Human Embryonic Stem Cell–Derived Teratoma Formation
- Author
-
Joseph C. Wu, Xiaoyuan Chen, Weibo Cai, Hui Wang, Kai Chen, Zhaofei Liu, Andrew Lee, Zibo Li, and Feng Cao
- Abstract
Teratoma formation can be a serious drawback after the therapeutic transplantation of human embryonic stem (hES) cells. Therefore, noninvasive imaging of teratomas could be a valuable tool for monitoring patients undergoing hES cell treatment. Here, we investigated the angiogenic process within teratomas derived from hES cells and now report the first example of using 64Cu-labeled RGD tetramer (64Cu-DOTA-RGD4) for positron emission tomography imaging of teratoma formation by targeting αvβ3 integrin. H9 hES cells (2 × 106), stably expressing firefly luciferase, and enhanced green fluorescence protein (Fluc-eGFP) were injected into adult nude mice (n = 12) s.c. Eight weeks after transplantation, these hES cell grafts evolved into teratomas as confirmed by longitudinal bioluminescence imaging. Under micropositron emission tomography imaging, 2-deoxy-2-[18F]fluoro-D-glucose and 3′-deoxy-3′-[18F]-fluorothymidine both failed to detect hES cell–derived teratomas (0.8 ± 0.5 versus 1.1 ± 0.4 %ID/g, respectively; P = not significant versus background signals). By contrast, 64Cu-DOTA-RGD4 revealed specific and prominent uptake in vascularized teratoma and significantly lower uptake in control tumors (human ovarian carcinoma 2008 cell line), which had low intergrin expression (10.1 ± 3.4 versus 1.4 ± 1.2 %ID/g; P < 0.01). Immunofluorescence staining of CD31 and β3 integrin also supported our in vivo imaging results (P < 0.05). Moreover, we found that the cells dissociated from teratomas showed higher αvβ3 integrin expression than the 2008 cells. In conclusion, by targeting αvβ3 integrin, we successfully showed the ability of 64Cu-DOTA-RGD4 to noninvasively visualize teratoma formation in vivo for the first time. [Cancer Res 2009;69(7):2709–13]
- Published
- 2023
10. Monoclonal Antibody against Cell Surface GRP78 as a Novel Agent in Suppressing PI3K/AKT Signaling, Tumor Growth, and Metastasis
- Author
-
Satyajit Sujit Kumar Mitra, Amy S. Lee, Shiuan Wey, Wenming Gao, Xiuqing Li, Yue Zhou, Peter S. Conti, Parkash S. Gill, Valery Krasnoperov, Ren Liu, Genyuan Zhu, Shuanglong Liu, Zibo Li, Dan Li, Dezheng Dong, and Stan G. Louie
- Subjects
Cancer Research ,Apoptosis ,Tumor M2-PK ,Antibodies, Monoclonal, Humanized ,Article ,Metastasis ,Mice ,Neoplasms ,medicine ,Animals ,Humans ,PTEN ,Neoplasm Metastasis ,Endoplasmic Reticulum Chaperone BiP ,Heat-Shock Proteins ,PI3K/AKT/mTOR pathway ,Cell Proliferation ,biology ,Cell growth ,Antibodies, Monoclonal ,Cancer ,medicine.disease ,Xenograft Model Antitumor Assays ,Molecular biology ,Elafin ,Oncology ,Tumor progression ,Cancer cell ,Cancer research ,biology.protein ,HT29 Cells ,Proto-Oncogene Proteins c-akt ,Signal Transduction - Abstract
Purpose: The ER chaperone GRP78 translocates to the surface of tumor cells and promotes survival, metastasis, and resistance to therapy. An oncogenic function of cell surface GRP78 has been attributed to the activation of the phosphoinositide 3-kinase (PI3K) pathway. We intend to use a novel anti-GRP78 monoclonal antibody (MAb159) to attenuate PI3K signaling and inhibit tumor growth and metastasis. Experimental Design: MAb159 was characterized biochemically. Antitumor activity was tested in cancer cell culture, tumor xenograft models, tumor metastasis models, and spontaneous tumor models. Cancer cells and tumor tissues were analyzed for PI3K activity. MAb159 was humanized and validated for diagnostic and therapeutic application. Results: MAb159 specifically recognized surface GRP78, triggered GRP78 endocytosis, and localized to tumors but not to normal organs in vivo. MAb159 inhibited tumor cell proliferation and enhanced tumor cell death both in vitro and in vivo. In MAb159-treated tumors, PI3K signaling was inhibited without compensatory MAPK pathway activation. Furthermore, MAb159 halted or reversed tumor progression in the spontaneous PTEN–loss-driven prostate and leukemia tumor models, and inhibited tumor growth and metastasis in xenograft models. Humanized MAb159, which retains high affinity, tumor specific localization, and the antitumor activity, was nontoxic in mice, and had desirable pharmacokinetics. Conclusions: GRP78-specific antibody MAb159 modulates the PI3K pathway and inhibits tumor growth and metastasis. Humanized MAb159 will enter human trials shortly. Clin Cancer Res; 19(24); 6802–11. ©2013 AACR.
- Published
- 2013
11. Cytoreductive Chemotherapy Improves the Biodistribution of Antibodies Directed against Tumor Necrosis in Murine Solid Tumor Models
- Author
-
Brian Wu, Alan L. Epstein, Leslie A. Khawli, Peter S. Conti, Ryan Park, Zibo Li, David Canter, and Julie K. Jang
- Subjects
Cancer Research ,Biodistribution ,Immunoconjugates ,medicine.medical_treatment ,Antineoplastic Agents ,Article ,Capillary Permeability ,Mice ,Necrosis ,chemistry.chemical_compound ,Neoplasms ,medicine ,Animals ,Humans ,Tissue Distribution ,Doxorubicin ,Etoposide ,Chemotherapy ,business.industry ,Antibodies, Monoclonal ,X-Ray Microtomography ,Immunotherapy ,Xenograft Model Antitumor Assays ,Vinblastine ,Radiation therapy ,Disease Models, Animal ,Oncology ,Paclitaxel ,chemistry ,Positron-Emission Tomography ,Immunology ,Cancer research ,Female ,business ,medicine.drug - Abstract
Current strategies in cancer treatment employ combinations of different treatment modalities, which include chemotherapy, radiotherapy, immunotherapy, and surgery. Consistent with that approach, the present study demonstrates how chemotherapeutic agents can potentiate the delivery of radiolabeled, necrosis-targeting antibodies (chTNT-3, NHS76) to tumor. All chemotherapeutics in this study (5-fluorouracil, etoposide, vinblastine, paclitaxel, and doxorubicin) resulted in statistically significant increases in tumor uptake of radiolabeled antibodies and their F(ab')2 fragments compared to no pretreatment with chemotherapy. Labeled antibodies were administered at various time points following a single dose of chemotherapy in multiple tumor models, and the biodistribution of the antibodies was determined by measuring radioactivity in harvested tissues. MicroPET/CT was also done to demonstrate clinical relevancy of using chemotherapy pretreatment to increase antibody uptake. Results of biodistribution and imaging data reveal specific time frames following chemotherapy when necrosis-targeting antibodies are best delivered, either for imaging or radiotherapy. Thus, the present work offers the prospect of using cytoreductive chemotherapy to increase tumor accumulation of select therapeutic antibodies, especially when combined with other forms of immunotherapy, for the successful treatment of solid tumors. Mol Cancer Ther; 12(12); 2827–36. ©2013 AACR.
- Published
- 2013
12. Noninvasive De novo Imaging of Human Embryonic Stem Cell–Derived Teratoma Formation
- Author
-
Weibo Cai, Joseph C. Wu, Zhaofei Liu, Kai Chen, Andrew S. Lee, Zibo Li, Feng Cao, Hui Wang, and Xiaoyuan Chen
- Subjects
CD31 ,Cancer Research ,Pathology ,medicine.medical_specialty ,Transplantation, Heterologous ,Mice, Nude ,Biology ,Article ,Heterocyclic Compounds, 1-Ring ,Mice ,Cell Line, Tumor ,Organometallic Compounds ,medicine ,Animals ,Humans ,Bioluminescence imaging ,neoplasms ,Embryonic Stem Cells ,Ovarian Neoplasms ,Integrin alphaVbeta3 ,Neovascularization, Pathologic ,Teratoma ,Endothelial Cells ,medicine.disease ,Embryonic stem cell ,Transplantation ,Cell Transformation, Neoplastic ,Copper Radioisotopes ,Oncology ,Positron-Emission Tomography ,Female ,Radiopharmaceuticals ,Stem cell ,Oligopeptides ,Preclinical imaging - Abstract
Teratoma formation can be a serious drawback after the therapeutic transplantation of human embryonic stem (hES) cells. Therefore, noninvasive imaging of teratomas could be a valuable tool for monitoring patients undergoing hES cell treatment. Here, we investigated the angiogenic process within teratomas derived from hES cells and now report the first example of using 64Cu-labeled RGD tetramer (64Cu-DOTA-RGD4) for positron emission tomography imaging of teratoma formation by targeting αvβ3 integrin. H9 hES cells (2 × 106), stably expressing firefly luciferase, and enhanced green fluorescence protein (Fluc-eGFP) were injected into adult nude mice (n = 12) s.c. Eight weeks after transplantation, these hES cell grafts evolved into teratomas as confirmed by longitudinal bioluminescence imaging. Under micropositron emission tomography imaging, 2-deoxy-2-[18F]fluoro-D-glucose and 3′-deoxy-3′-[18F]-fluorothymidine both failed to detect hES cell–derived teratomas (0.8 ± 0.5 versus 1.1 ± 0.4 %ID/g, respectively; P = not significant versus background signals). By contrast, 64Cu-DOTA-RGD4 revealed specific and prominent uptake in vascularized teratoma and significantly lower uptake in control tumors (human ovarian carcinoma 2008 cell line), which had low intergrin expression (10.1 ± 3.4 versus 1.4 ± 1.2 %ID/g; P < 0.01). Immunofluorescence staining of CD31 and β3 integrin also supported our in vivo imaging results (P < 0.05). Moreover, we found that the cells dissociated from teratomas showed higher αvβ3 integrin expression than the 2008 cells. In conclusion, by targeting αvβ3 integrin, we successfully showed the ability of 64Cu-DOTA-RGD4 to noninvasively visualize teratoma formation in vivo for the first time. [Cancer Res 2009;69(7):2709–13]
- Published
- 2009
13. Imaging of Urokinase-Type Plasminogen Activator Receptor Expression Using a 64Cu-Labeled Linear Peptide Antagonist by microPET
- Author
-
Hui Wang, Lina He, Xiaoyuan Chen, Lily Yang, Michael Ploug, Zibo Li, and Gang Niu
- Subjects
Cancer Research ,Receptor expression ,Mice, Nude ,Receptors, Cell Surface ,Biology ,Receptors, Urokinase Plasminogen Activator ,Metastasis ,Heterocyclic Compounds, 1-Ring ,Mice ,chemistry.chemical_compound ,Cell surface receptor ,In vivo ,Cell Line, Tumor ,medicine ,Animals ,Humans ,DOTA ,skin and connective tissue diseases ,neoplasms ,Urokinase ,Reverse Transcriptase Polymerase Chain Reaction ,Surface Plasmon Resonance ,medicine.disease ,biological factors ,Urokinase receptor ,Kinetics ,Copper Radioisotopes ,Oncology ,chemistry ,Biochemistry ,Positron-Emission Tomography ,Cancer research ,Female ,biological phenomena, cell phenomena, and immunity ,Peptides ,Plasminogen activator ,Neoplasm Transplantation ,medicine.drug - Abstract
Purpose: Malignant tumors are capable of degrading the surrounding extracellular matrix, resulting in local invasion or metastasis. Urokinase-type plasminogen activator (uPA) and its cell surface receptor (uPAR) are central molecules in one of the major protease systems involved in extracellular matrix degradation. Noninvasive imaging of this receptor in vivo with radiolabeled peptides that specifically target uPAR may therefore be useful to decipher the potential invasiveness of malignant lesions. Experimental Design: In this study, we developed a 64Cu-labeled uPAR-binding peptide for positron emission tomography (PET) imaging. A linear, high-affinity uPAR-binding peptide antagonist AE105 was conjugated with 1,4,7,10-tetraazadodecane-N,N′,N″,N‴-tetraacetic acid (DOTA) and labeled with 64Cu for microPET imaging of mice bearing U87MG human glioblastoma (uPAR positive) and MDA-MB-435 human breast cancer (uPAR negative). Results: Surface plasmon resonance measurements show that AE105 with DOTA conjugated at the α-amino group (DOTA-AE105) has high affinity toward uPAR. microPET imaging reveals a rapid and high accumulation of 64Cu-DOTA-AE105 in uPAR-positive U87MG tumors (10.8 ± 1.5%ID/g at 4.5 hours, n = 3) but not in uPAR-negative MDA-MB-435 tumors (1.2 ± 0.6%ID/g at 4.5 hours, n = 3). Specificity of this peptide-based imaging of uPAR was validated by further control experiments. First, a nonbinding variant of AE105 carrying a single amino acid replacement (Trp→Glu) does not target U87MG tumors in vivo. Second, targeting of U87MG tumors by 64Cu-DOTA-AE105 is specifically inhibited by a nonlabeled antagonist. Conclusion: The successful demonstration of the ability of a 64Cu labeled uPAR-specific probe to visualize uPAR expression in vivo may allow clinical translation of this class of radiopharmaceuticals for uPAR-positive cancer detection and patient stratification for uPA/uPAR system-based cancer therapy.
- Published
- 2008
14. Integrin-targeted imaging and therapy with RGD4C-TNF fusion protein
- Author
-
Hui Wang, Kai Chen, Xiaoyuan Chen, Zibo Li, Lina He, Weibo Cai, and Amir Kashefi
- Subjects
Cancer Research ,Recombinant Fusion Proteins ,Alpha (ethology) ,Antineoplastic Agents ,Biology ,Sensitivity and Specificity ,Heterocyclic Compounds, 1-Ring ,Mice ,In vivo ,Cell Line, Tumor ,Organometallic Compounds ,Animals ,Humans ,Tissue Distribution ,Cytotoxicity ,Receptor ,Chelating Agents ,Tumor Necrosis Factor-alpha ,Integrin alphaVbeta3 ,Fusion protein ,Molecular biology ,Copper Radioisotopes ,Oncology ,Cell culture ,Positron-Emission Tomography ,Female ,Tumor necrosis factor alpha ,Ex vivo - Abstract
This study used integrin αvβ3 as a target for tumor-specific delivery of tumor necrosis factor-α (TNF). The fusion protein RGD4C-TNF bound specifically to αvβ3 as evidenced by cell receptor binding assay and noninvasive micro-positron emission tomography imaging. 64Cu-DOTA-RGD4C-TNF had significantly higher activity accumulation in integrin-positive tumors (U87MG and MDA-MB-435) but not in integrin-negative tumors (C6) compared with 64Cu-DOTA-TNF. The magnitude of tumor uptake of 64Cu-DOTA-RGD4C-TNF correlated well with the αvβ3 level (U87MG > MDA-MB-435 > C6). Tumor accumulation of 64Cu-DOTA-RGD4C-TNF could be effectively blocked by c(RGDyK) peptide in αvβ3-positive tumor models, suggesting αvβ3 specificity of RGD4C-TNF fusion protein in vivo. Furthermore, although the fusion of RGD4C moiety to TNF had little effect on the bioactivity and cytotoxicity of RGD4C-TNF compared with TNF in cell culture, RGD4C-TNF was significantly more potent than TNF in inhibiting orthotopic MDA-MB-435 tumor growth. Ex vivo tissue staining confirmed specific cytotoxicity of RGD4C-TNF against integrin-positive tumor cells and tumor vasculature. [Mol Cancer Ther 2008;7(5):1044–53]
- Published
- 2008
15. Abstract 4893: High-throughput mutation sequencing of the full exon regions in BRCA1 and BRCA2 genes using nanofluidic-PCR prepared libraries
- Author
-
Lili Tang, Ming Chen, Fan Zhang, Zibo Li, Limin Peng, Lizhong Dai, Xinwu Guo, Zhi Xiao, Jianfu Heng, Wenjun Yi, Guoli Li, Shouman Wang, and Jun Wang
- Subjects
Genetics ,Cancer Research ,endocrine system diseases ,Cancer ,Amplicon ,Biology ,medicine.disease ,Exon ,Germline mutation ,Breast cancer ,Oncology ,Mutation (genetic algorithm) ,medicine ,Primer (molecular biology) ,skin and connective tissue diseases ,Illumina dye sequencing - Abstract
Breast cancer is one of the most common cancers and also the principal cause of cancer-related death among women in the world. BRCA1 and BRCA2 genes contribute to DNA repair and transcriptional regulation in response to DNA damage. Mutations of BRCA1/2 genes greatly increase lifetime risk to develop breast cancer and these mutations are frequently observed in hereditary breast cancer. In addition, recent studies suggested that breast cancer patients who carry a BRCA1 or BRCA2 germline mutation benefit from poly (ADP-ribose) polymerase (PARP) inhibitors. Therefore, it would be of great interest to develop a high-throughput approach for mutation screening of the full exon regions in BRCA1 and BRCA2 gene. We have developed a targeted gene exon-sequencing approach using a nanofluidic PCR platform, the Access Array™ system, which enables simultaneous amplification of 48 genetic regions (amplicons) from 48 samples in parallel. We have applied this system to generate the libraries of BRCA1 and BRCA2 coding regions. Total 120 target-specific primer pairs were designed covering all 22 exons of BRCA1 and 26 exons of BRCA2. A primer design strategy was applied to incorporate sample-specific barcodes and Illumina sequencing adaptors into each amplicon, allowing direct sequencing without further library preparation. The exon regions of these 2 genes have been amplified on Access Arrays using 48 multiplex mixes of the 120 primer sets in paired tumor/normal tissues from 144 breast cancer patients. We will present the next-generation sequencing data of BRCA1 and BRCA2 mutation screening collected from amplicon libraries generated using the Access Array system. Our results indicate the excellent utilization of this approach in the mutation screening of BRCA1 and BRCA2 in clinical samples. Note: This abstract was not presented at the meeting. Citation Format: Jun Wang, Guoli Li, Ming Chen, Jianfu Heng, Xinwu Guo, Limin Peng, Fan Zhang, Zibo Li, Shouman Wang, Zhi Xiao, Lizhong Dai, Wenjun Yi, Lili Tang. High-throughput mutation sequencing of the full exon regions in BRCA1 and BRCA2 genes using nanofluidic-PCR prepared libraries. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4893. doi:10.1158/1538-7445.AM2015-4893
- Published
- 2015
16. Abstract 293: High-throughput methylation sequencing of targeted genes in breast cancer specimens using nanofluidic PCR prepared libraries
- Author
-
Zhongping Deng, Zhi Xiao, Yepeng Wu, Shengyun Li, Zibo Li, Lizhong Dai, Feiyu Chen, Jun Wang, Wenjun Yi, Xinwu Guo, and Lili Tang
- Subjects
Genetics ,Cancer Research ,Candidate gene ,Cancer ,Amplicon ,Biology ,medicine.disease ,medicine.disease_cause ,DNA sequencing ,Breast cancer ,Oncology ,medicine ,Illumina Methylation Assay ,Epigenetics ,Carcinogenesis - Abstract
Breast cancer is a global public health issue as it is the most frequently diagnosed malignancy in women in the Western world with over a million new cases every year worldwide. Previous epigenetic analyses have identified aberrant DNA methylation signatures associated with breast cancer. Methylation alterations resulting in aberrant gene expression are key contributors to breast tumorigenesis. There are more than 100 candidate genes reported throughout the literatures as promoter hypermethylated in breast cancers (Pubmeth web resource). More recently, with the application of genome wide array-based methylation profile analysis and next generation sequencing, hundreds of new methylation candidate genes have been reported to be associated with breast cancer. It is crucial to develop an approach for targeted methylaton resequencing to validate these candidate genes in hundreds of patient samples and develop a breast cancer detection panel for early diagnostics. We have developed a targeted gene bisulfite-sequencing approach using a nanofluidic platform, the Access Array™ system, which enables simultaneous amplification of 48 genetic regions (amplicon) from 48 samples in parallel. We have selected 48 breast cancer associated methylation candidate genes, each commonly reported by multiple literatures. Bisulfite-specific-sequencing (BSP) primers were designed for the promoter regions of these genes. In addition, we have applied a primer design strategy that incorporates sample-specific barcodes and Illumina (Miseq) sequencing adaptors into each amplicon, removing the need for additional library preparation before sequencing. We will present methylation sequencing data collected from amplicon libraries generated using the Access Array system. The 48 promoter regions have been amplified in paired tumor/normal tissues and plasma DNA from 48 breast cancer patients. Our results indicate the excellent utilization of this approach in the validation of methylation biomarkers and selection of detection panel for breast cancer. Citation Format: Jun Wang, Zibo Li, Yepeng Wu, Xinwu Guo, Shengyun Li, Zhi Xiao, Feiyu Chen, Zhongping Deng, Lizhong Dai, Wenjun Yi, Lili Tang. High-throughput methylation sequencing of targeted genes in breast cancer specimens using nanofluidic PCR prepared libraries. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 293. doi:10.1158/1538-7445.AM2014-293
- Published
- 2014
17. Abstract 5248: A novel ovarian cancer imaging agent based on integrin ligation
- Author
-
Francis S. Markland, Radu O. Minea, Zibo Li, and Stephen Swenson
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,Pathology ,biology ,business.industry ,Ultrasound ,Integrin ,Cancer ,medicine.disease ,Imaging agent ,Ovarian tumor ,Internal medicine ,medicine ,biology.protein ,Luciferase ,business ,Ovarian cancer ,Ligation - Abstract
Ovarian cancer diagnosis and subsequent evaluation of disease progression is difficult due to the location of tumor mass and access to the organs affected. Ultrasound and surgical exposure are required to confirm disease and response to treatment. In an effort to develop a non-invasive radiologic method for both diagnostic assessment and to follow disease progression we have produced a integrin ligand, vicrostatin (VCN) that can be radiolabeled and imaged upon binding to active integrins over-expressed on the tumor. VCN displays a high affinity for integrins which are active and pivotal in tumor growth and progression. In the present studies we utilized an animal model employing the luciferase expressing cell line OVCAR-3luc. This procedure allows us to observe both the tumor itself in a living animal, and also co-register the PET image with the optical image enabling us to detect tumors in the intraperitoneal (IP) space. For these experiments we injected OVCAR-3luc cells IP and allowed the tumors to age for 28 days. At this point, with no obvious sign of disease, we imaged the tumors using the optical imaging system to detect the presence of luciferase. Since luciferase is only found in the tumor, this enables us to specifically image the tumor. Following these images 64Cu-DOTA-VCN is injected into the tail vein of the study animals and allowed to circulate for 90 minutes. At this time the animal is placed onto the mounting tray of the PET imaging instrument. There is a specific accumulation of 64Cu-DOTA-VCN in an area in the lower abdomen that correlates with a location of luciferase activity seen in the optical image. Both of these positions were confirmed by dissection and exposure of the tumor in the sacrificed animal. Experiments in which a larger number of cells are injected IP produced unusable optical images, as the tumors grew very large and coated much of the surface in the IP space yielding bright and indistinguishable images in the mouse abdomen. One problem of note is the high level of uptake by the kidneys at the 90 minute time point. The kidneys shield the ability to view an ovarian tumor via a dorsal or ventral total slice view. When viewed transversely, there is clear separation between the kidneys and the tumor mass which binds the 64Cu-DOTA-VCN. A three dimensional reconstruction yields a three dimensional model that can be rotated and rendered to observe the position of the tumor in relationship to the kidneys in space. These studies show that VCN can be utilized to image early stage OC and could possibly be used to monitor residual disease after surgical or therapeutic intervention. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5248. doi:1538-7445.AM2012-5248
- Published
- 2012
18. Abstract 370: Tetrazine trans-cyclooctene ligation: An efficient 18F labeling method for cysteine containing peptides and proteins
- Author
-
Ramajeyam Selvaraj, Joseph M. Fox, Shuanglong Liu, Matt Hassink, Zibo Li, Xiaoyuan Chen, Peter S. Conti, and Li-Peng Yap
- Subjects
Cancer Research ,biology ,Stereochemistry ,VEGF receptors ,Tetrazine ,chemistry.chemical_compound ,Oncology ,Biochemistry ,chemistry ,Nucleophile ,18f labeling ,Cyclooctene ,Yield (chemistry) ,biology.protein ,Ligation ,Cysteine - Abstract
18F PET has a number of attributes that make it clinically attractive, including almost 100% positron efficiency, very high specific radioactivity, and short half-life of ∼110 min. However, the short half-life of 18F and the poor nucleophilicity of fluoride make it difficult to incorporate 18F in complex molecules. Recently, the tetrazine-trans-cyclooctene ligation has been introduced as a novel 18F labeling method that proceeds with fast reaction rates without any catalysis. To further explore the scope of this reaction, herein we reported an efficient method for 18F-lableing of free cysteine-containing bioligands based on the tetrazine-trans-cyclooctene ligation. The newly developed method was tested for site specific labeling of both c(RGDyC) and VEGF-SH protein. Starting with 4 mCi of 18F-trans-cyclooctene and only 10 μg of tetrazine-RGD (80-100 µM) or 15 μg of tetrazine-VEGF (6.0 µM), the 18F labeled RGD peptide or VEGF protein could be obtained in 95% yield and 75% yield within five minutes. The obtained tracers were then evaluated in small animals. In conclusion, a highly efficient method has been developed for site-specific 18F labeling of cysteine containing peptides and proteins. The special characteristics of the tetrazine-trans-cyclooctene ligation provide unprecedented opportunities to synthesize 18F-labeled probes with high specific activity for PET applications. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 370. doi:1538-7445.AM2012-370
- Published
- 2012
19. Abstract 5731: PET and fluorescence imaging of brain cancer with a dual modality probe based on sarcophagine cage
- Author
-
Li-Peng Yap, Zibo Li, Chiun-Wei Huang, Peter S. Conti, Shuanglong Liu, and Ryan Park
- Subjects
Cancer Research ,Fluorescence-lifetime imaging microscopy ,Oncology ,business.industry ,Dual modality ,Medicine ,Sarcophagine ,business ,Nuclear medicine ,Brain cancer - Abstract
The development of a PET/optical imaging system is attractive because of the opportunity to obtain complementary data from two similar contrast mechanisms using one probe. Different from PET/CT or SPECT/CT, a linker is generally needed to efficiently incorporate PET tag, optical tag, and the biomarker together. Previously we developed a dicarboxyl-functionalized chelator (BaBaSar) derivatized from sarcophagine cage (denoted as Sar). BaBaSar has been used for 64Cu radiopharmaceutical development and the great in vivo stability of 64Cu-BaBaSar encouraged us to continue to derivatize the sarcophagine core for versatile conjugation styles with biomarkers. In this study, we synthesized a hetero-functionalized sarcophagine named BaAnSar: carboxyl group at one end of the Sar cage and amino group on the other end. The pendant hetero-arm could be further conjugated to multiple targeting ligands via biologically stable amide bonds. In order to prove the advantage of the this BaAnSar chelator, we chose dimeric c(RGDyK) peptide (denoted as RGD2), a well-known ligand targeting integrin αvβ3, onto the carboxyl side and fluorescent dye Cy5.5 on the amino functional side of the Sar cage. After labeling with 64Cu, a dual-modality probe, 64Cu-BaAnSar-RGD2-Cy5.5 was made and evaluated in U87MG tumor bearing nude mice. Both NIR fluorescence imaging and microPET clearly delineated the U87MG tumor from the surrounded normal tissue at 1, 4, and 20 h post injection of 64Cu-BaAnSar-RGD2-Cy5.5. The microPET quantification of U87MG tumor uptake was determined as 6.41 ± 0.28, 6.51 ± 1.45, and 5.92 ± 1.57 %ID/g at 1, 4, and 20 h post injection, respectively. Good correlation was also observed between the results measured by ex vivo PET and NIRF organ imaging. In conclusion, we have successfully developed a bifunctional chelator for dual PET and NIRF imaging probe construction. The BaAnSar chelator developed herein has the potential to enhance resolution for comprehensive visualization of the probe distribution and provides a rapid and efficient imaging method for basic research and potential clinical applications, especially as a visual guide during surgery. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5731. doi:1538-7445.AM2012-5731
- Published
- 2012
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.