9 results on '"Yu, Yi"'
Search Results
2. The effect of PAFR on cisplatin sensitivity in ovarian cancer cells and its mechanism.
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YU Yi, CONG Qing, XU Congjian, and JIANG Wei
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Background and purpose: The current treatment of ovarian cancer is surgery and adjuvant platinum-based chemotherapy. However, relapse and drug resistance are common. We have demonstrated the platelet-activating factor receptor (PAFR) is highly expressed in epithelial ovarian cancer, promoting ovarian cancer cell proliferation and invasion. The objective was to explore the effect of PAFR expression on cisplatin (CDDP) in ovarian cancer cells to provide novel theoretical basis for ovarian cancer therapy. Methods: The upregulation of PAFR in CDDP-treated ovarian cancer cells was observed using Western blot and real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR). The role of nuclear factor Kappa-B (NF-κB)/p65 and hypoxia inducible factor-1α (HIF-1α) in modulating PAFR expression was assessed using Western blot, siRNA and immunofluorescence. The effect of PAFR on CDDP sensitivity was observed using a pharmacological inhibitor and siRNA knockdown. Results: CDDP induced dose- and timedependent upregulation of PAFR in two ovarian cancer cell lines (P<0.01). The downregulation of PAFR by CDDP correlated with the inhibitions of NF-κB and HIF-1α which were accumulated by CDDP in the nucleus. Inhibition of PAFR expression by PAFR specific small molecule antagonist WEB2086 or RNA interference could significantly improve the sensitivity of ovarian cancer cells to CDDP. The cell proliferation ability decreased significantly (P<0.01), while the apoptotic rate increased significantly (P<0.01). Increased expression of PAFR activated downstream AKT and ERK pathways in CDDP-treated cells. Conclusion: CDDP induces upregulation of PAFR by accumulating NF-κB and HIF-1α in the nucleus. PAFR inhibition may modulate the CDDP sensitivity in ovarian cancer cells, which is a novel and promising therapeutic target for sensitizing ovarian cancer cells to CDDP. [ABSTRACT FROM AUTHOR]
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- 2021
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3. Abstract 5682: Synergism of PARP inhibitor and MET inhibitor in multiple cancer types with intrinsic and acquired PARP inhibitor resistances
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Ye Han, Yuan Gao, Weiya Xia, Qiongzhu Dong, Hung-Ling Wang, Yu-Yi Chu, Mien Chie Hung, Yongkun Wei, Clinton Yam, Yu-Han Wang, Mei-Kuang Chen, Funda Meric-Bernstam, Yi Du, Coya Tapia, Jinsong Liu, Dihua Yu, and Shao Chun Wang
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Cancer Research ,business.industry ,medicine.medical_treatment ,Estrogen receptor ,Cancer ,medicine.disease ,Targeted therapy ,Breast cancer ,Oncology ,PARP inhibitor ,Cancer cell ,Cancer research ,Medicine ,business ,Ovarian cancer ,Triple-negative breast cancer - Abstract
Leveraging compromised DNA damage repair (DDR) pathways commonly found in tumor cells, a classic strategy in cancer therapy is inducing excessive DNA damage to cause cancer cell death. Small molecule poly(ADP-ribose) polymerase (PARP) inhibitors (PARP-is) have been approved for clinical use in treating breast cancer and ovarian cancer patients bearing DDR-deficient tumors with mutations in breast cancer susceptibility proteins (BRCAm). However, accumulating evidences show that both intrinsic and acquired resistances to PARP-is exist in clinic and pre-clinical animal models. Therefore, we developed panels of cells with acquired PARP-is resistance from PARP-is-sensitive triple negative breast cancer (TNBC) and estrogen receptor positive breast cancer cell lines, and used these cells to screen for common traits that can be targeted with feasible therapeutic agent combinations to overcome PARP-is resistance. Since TNBC lacks of effective targeted therapy so far, we focused on using the panel of PARP-is-resistant TNBC cells in this study. Among the molecular mechanisms known contribute to PARP-is resistance, oncogenic kinase activations, including several hyper-activated receptor tyrosine kinases (RTKs), are involved in enhancing DNA damage repair and decreasing affinity of PARP-is to PARP1. In this study, we systematically screened for activated RTKs in the PARP-is-resistant cells we developed by antibody arrays. We then identified that activations of MET, Axl and EphA2 were common traits in TNBC cells with acquired PARP-is resistance, but not in estrogen receptor positive cells. Among the three RTKs, MET has more small molecules inhibitors that can target it, and thus, we made it a priority in investigating synergism between MET inhibitor and PARP inhibitor in multiple cancer types including TNBC with intrinsic and acquired PARP-is-resistance, high-grade serous ovarian cancer (HGSOC) and liver cancer cells. Here, we demonstrated that combinations of PARP-is and MET inhibitors (MET-is) possess moderate to strong synergism in the different cancer types we studied. As we previously reported that MET translocates into cell nucleus and phosphorylates PARP1 at tyrosine (Y) 907 residue in TNBC with intrinsic PARP-is resistance, we found that this MET-mediated PARP1-Y907 phosphorylation also exist in and can serve as marker to indicate PARP-is resistance among the HGSOC, liver cancer cells and the TNBC cells with acquired PARP-is resistance. We further found that MET phosphorylation is high (immunohistological staining H-score greater than 200) in breast cancer (23 out of 31, 70%) and ovarian cancer (8 out of 23, 35%) patient-derived xenograft mouse model tissue microarrays, suggesting that the combination of MET-is and PARP-is is likely to benefit a huge population of cancer patient in multiple cancer types. Citation Format: Mei-Kuang Chen, Weiya Xia, Qiongzhu Dong, Yi Du, Hung-Ling Wang, Coya Tapia, Yongkun Wei, Ye Han, Yu-Yi Chu, Clinton Yam, Yuan Gao, Yu-Han Wang, Funda Meric-Bernstam, Jinsong Liu, Shao-Chun Wang, Dihua Yu, Mien-Chie Hung. Synergism of PARP inhibitor and MET inhibitor in multiple cancer types with intrinsic and acquired PARP inhibitor resistances [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5682.
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- 2020
4. Retro-inverso follicle-stimulating hormone peptide-mediated polyethylenimine complexes for targeted ovarian cancer gene therapy.
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Zhang, Mengyu, Zhang, Mingxing, Wang, Jing, Cai, Qingqing, Zhao, Ran, Yu, Yi, Tai, Haiyan, Zhang, Xiaoyan, and Xu, Congjian
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OVARIAN cancer ,CANCER chemotherapy ,GENE expression ,ANTINEOPLASTIC agents ,CELL proliferation - Abstract
Background: The development of nanoparticle drug delivery systems with targeted ligands has the potential to increase treatment efficiency in ovarian cancer. Methods: We developed a 21-amino acid peptide, YTRDLVYGDPARPGIQGTGTF (L-FP21) conjugated to polyethylenimine (PEI) and methoxy polyethylene glycol (mPEG) to prepare a nanoparticle drug vehicle to target follicle-stimulating hormone receptor (FSHR) in ovarian cancer. At the same time, we optimized the ligand of the nanoparticle vehicle using D-peptides, which consist of D-amino acids (D-FP21). Nanoparticle vehicles carrying the therapeutic gene plasmid growth-regulated oncogene alpha (pGRO-α) short hairpin RNA (shRNA) (FP21-PEG-PEI/pGRO-α) were prepared for further investigation. Results: Compared with L-FP21, D-FP21 exhibited improved biological stability and higher uptake rate for FSHR-expressing ovarian cancer cells. The cytotoxicity of the L, D-FP21-PEG-PEI/pGRO-α complexes were significantly lower than that of the PEI/pGRO-α complex. The nanoparticle drug with the targeted ligand showed higher transfection efficiencies and improved anti-proliferation effects for ovarian cancer cells than that without the targeted ligand (mPEG-PEI/pGRO-α). Furthermore, an in vivo evaluation of an antitumor assay indicated that D-FP21-PEG-PEI/pGRO-α inhibited the growth of tumor spheroids considerably more than L-FP21-PEG-PEI/pGRO-α; their tumor inhibition rates were 58.5% and 33.3%, respectively. Conclusions: D-FP21-PEG-PEI/plasmid DNA is a safe and efficient gene delivery vehicle for ovarian cancer targeted therapy. [ABSTRACT FROM AUTHOR]
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- 2018
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5. Follicle-stimulating hormone peptide-conjugated nanoparticles for targeted shRNA delivery lead to effective gro-α silencing and antitumor activity against ovarian cancer.
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Hong, Shan-Shan, Zhang, Ming-Xing, Zhang, Meng, Yu, Yi, Chen, Jun, Zhang, Xiao-Yan, and Xu, Cong-Jian
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OVARIAN cancer ,CANCER chemotherapy ,CELL proliferation ,BREAST cancer ,MICRORNA - Abstract
The distinct hormone molecules and receptors, such as follicle-stimulating hormone receptor (FSHR) in ovarian cancer, provide opportunities for more precisely targeted therapy. We previously developed FSHR-mediated nanoparticles and found that FSH peptides on the surface of nanoparticles improved the delivery of short interfering RNA (siRNA) into ovarian cancer cells. However, the high toxicity of the nanoparticles and the transient silencing of the siRNA in vivo limited further study. Here, we developed FSH peptide-conjugated nanoparticles with an increased amount of polyethylene glycol (PEG) grafting and encapsulated short hairpin RNA (shRNA) to silence the target gene, growth-regulated oncogene α (gro-α). The nanoparticle complexes exhibited good stability over three weeks. Expression of the target gene, gro-α, was significantly down-regulated by gro-α shRNA-loaded nanoparticles conjugated with FSH peptides (FSH33-G-NP) in FSHR-positive HEY cells. Cell proliferation, migration, and invasion were also inhibited by FSH33-G-NP. Tumor growth was delayed significantly in the mice treated with FSH33-G-NP. No significant loss of body weight or severe toxic effects were observed in any groups. In conclusion, gro-α shRNA-loaded nanoparticles conjugated with FSH peptides overcame the drawbacks of the in vivo application of RNAi therapeutics and polymer-based nanocarriers and showed safe antitumor efficacy. Our study might contribute to the application of FSHR-based targeted therapy and imaging in cancer. [ABSTRACT FROM AUTHOR]
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- 2018
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6. Immune Cells in the Normal Ovary and Spontaneous Ovarian Tumors in the Laying Hen (Gallus domesticus) Model of Human Ovarian Cancer.
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Bradaric, Michael J., Penumatsa, Krishna, Barua, Animesh, Edassery, Seby L., Yu, Yi, Abramowicz, Jacques S., Bahr, Janice M., and Luborsky, Judith L.
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OVARIAN cancer ,CHICKENS as laboratory animals ,LYMPHOCYTES ,CANCER invasiveness ,DOPPLER ultrasonography ,IMMUNE response - Abstract
Background: Spontaneous ovarian cancer in chickens resembles human tumors both histologically and biochemically. The goal was to determine if there are differences in lymphocyte content between normal ovaries and ovarian tumors in chickens as a basis for further studies to understand the role of immunity in human ovarian cancer progression. Methods: Hens were selected using grey scale and color Doppler ultrasound to determine if they had normal or tumor morphology. Cells were isolated from ovaries (n = 6 hens) and lymphocyte numbers were determined by flow cytometry using antibodies to avian CD4 and CD8 T and B (Bu1a) cells. Ovarian sections from another set of hens (n = 26) were assessed to verify tumor type and stage and to count CD4, CD8 and Bu1a immunostained cells by morphometric analysis. Results: T and B cells were more numerous in ovarian tumors than in normal ovaries by flow cytometry and immunohistochemistry. There were less CD4+ cells than CD8+ and Bu1a+ cells in normal ovaries or ovarian tumors. CD8+ cells were the dominant T cell sub-type in both ovarian stroma and in ovarian follicles compared to CD4+ cells. Bu1a+ cells were consistently found in the stroma of normal ovaries and ovarian tumors but were not associated with follicles. The number of immune cells was highest in late stage serous tumors compared to endometrioid and mucinous tumors. Conclusions: The results suggest that similar to human ovarian cancer there are comparatively more immune cells in chicken ovarian tumors than in normal ovaries, and the highest immune cell content occurs in serous tumors. Thus, this study establishes a foundation for further study of tumor immune responses in a spontaneous model of ovarian cancer which will facilitate studies of the role of immunity in early ovarian cancer progression and use of the hen in pre-clinical vaccine trials. [ABSTRACT FROM AUTHOR]
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- 2013
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7. Sphingosine-1 phosphate receptor (S1p1), a critical receptor controlling human lymphocyte trafficking, is expressed in hen and human ovaries and ovarian tumors
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Michael J. Bradaric, Jacques S. Abramowicz, Judith L. Luborsky, Janice M. Bahr, Seby L. Edassery, Animesh Barua, Sameer Sharma, Yu Yi, and Krishna Penumatsa
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0303 health sciences ,Sphingosine-1-phosphate receptor ,Lymphocyte ,Research ,Obstetrics and Gynecology ,Ovary ,Biology ,medicine.disease ,lcsh:Gynecology and obstetrics ,Metastasis ,03 medical and health sciences ,Ovarian tumor ,0302 clinical medicine ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,Immunology ,Obstetrics and Gynaecology ,Cancer research ,medicine ,Receptor ,Ovarian cancer ,Peripheral lymph ,lcsh:RG1-991 ,030304 developmental biology - Abstract
Background Sphingosine-1 receptor 1 (S1P1) plays a major role in regulating lymphocyte egress from peripheral lymph tissue. Lymphocyte trafficking is potentially a critical response to tumors and to tumor vaccines. Also, the receptor has been shown to influence metastasis. However, there is little information on its expression in the aged ovary or ovarian tumors. As a basis for further studies in the laying hen model of spontaneous ovarian cancer, the objective of this study was to determine if S1P1 is expressed in hens, and if the morphological distribution of S1P1 is similar in hen and human ovary and ovarian tumors. Methods S1P1 mRNA was ascertained in hen tissue by RT-PCR using hen specific primers. S1P1 protein expression and localization was evaluated in hen and human tissue with a human S1P1 antibody by Western blot and immunohistochemistry. Results S1P1 mRNA was expressed in all hen tissues examined. Protein was detected in human and hen ovary and ovarian tumors at 47, 72 and 108 kDa in Western blots. S1P1 was similarly expressed on endothelial cells, lymphocytes and surface epithelial cells in normal ovaries and tumor-containing ovaries of the hen. In addition, S1P1 distribution was heterogeneous in both hen and human ovarian tumors by immunohistochemistry. Conclusion The results show that S1P1 is expressed in the hen and human ovary as well as in ovarian tumors. These findings support the use of the hen in further studies of the role of S1P1 in metastasis and immune cell trafficking in ovarian tumor development.
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8. Folate-linked lipoplexes for short hairpin RNA targeting claudin-3 delivery in ovarian cancer xenografts.
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He, Zhi-Yao, Wei, Xia-Wei, Luo, Min, Luo, Shun-Tao, Yang, Yang, Yu, Yi-Yi, Chen, Yan, Ma, Cui-Cui, Liang, Xiao, Guo, Fu-Chun, Ye, Ting-Hong, Shi, Hua-Shan, Shen, Guo-Bo, Wang, Wei, Gong, Feng-Ming, He, Gu, Yang, Li, Zhao, Xia, Song, Xiang-Rong, and Wei, Yu-Quan
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OVARIAN cancer treatment , *FOLIC acid , *RNA , *CLAUDINS , *XENOGRAFTS , *CANCER invasiveness - Abstract
Abstract: Ovarian cancers highly overexpress folate receptor α (FRα) and claudin3 (CLDN3), both of which are associated with tumor progression and poor prognosis of patients. Downregulation of FRα and CLDN3 in ovarian cancer may suppress tumor growth and promote benign differentiation of tumor. In this study, F-P-LP/CLDN3, a FRα targeted liposome loading with short hairpin RNA (shRNA) targeting CLDN3 was prepared and the pharmaceutical properties were characterized. Then, the antitumor effect of F-P-LP/CLDN3 was studied in an in vivo model of advanced ovarian cancer. Compared with Control, F-P-LP/CLDN3 promoted benign differentiation of tumor and achieved about 90% tumor growth inhibition. In the meantime, malignant ascites production was completely inhibited, and tumor nodule number and tumor weight were significantly reduced (p<0.001). FRα and CLDN3 were downregulated together in tumor tissues treated by F-P-LP/CLDN3. The antitumor mechanisms were achieved by promoting tumor cell apoptosis, inhibiting tumor cell proliferation and reducing microvessel density. Finally, safety evaluation indicated that F-P-LP/CLDN3 was a safe formulation in intraperitoneally administered cancer therapy. We come to a conclusion that F-P-LP/CLDN3 is a potential targeting formulation for ovarian cancer gene therapy. [Copyright &y& Elsevier]
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- 2013
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9. The hen model of human ovarian cancer develops anti-mesothelin autoantibodies in response to mesothelin expressing tumors
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Yu Yi, Edassery Seby L, Barua Animesh, Abramowicz Jacques S, Bahr Janice M, Hellstrom Ingegerd, and Luborsky Judith L
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Mesothelin ,Mesothelin antibodies ,Ovarian Cancer ,Hens ,Animal Model ,Gynecology and obstetrics ,RG1-991 - Abstract
Abstract Objective Study of the hen immune system led to seminal contributions to basic immunological principles. Recent studies of spontaneous ovarian cancer in the laying hen show strikingly similar tumor types and antigen expression compared to human ovarian cancer, suggesting hens would be valuable for studies of tumor immunology and pre-clinical vaccine development. Circulating mesothelin is a relatively specific marker for human ovarian cancer and autoantibodies to mesothelin were reported. We hypothesized that hen tumors express mesothelin and that circulating anti-mesothelin antibodies occur in response to tumors. Methods Mesothelin mRNA expression was analyzed by RT-PCR in hen ovarian tumors and normal ovaries. Mesothelin protein expression was evaluated by immunohistochemistry (IHC) and two-dimensional SDS-PAGE Western blots. Anti-mesothelin antibodies were assessed by immunoassay of sera from hens with normal ovaries and with ovarian tumors. Results Significant mesothelin mRNA expression was observed in 57% (12/21) of hen ovarian tumors but not in normal ovaries and was found predominantly in serous tumors as in humans. Mesothelin protein was detected in tumors with mesothelin mRNA by IHC and 2D Western blots, but not in normal ovaries or tumors without mesothelin mRNA. Circulating anti-mesothelin antibodies occurred in 44% (n = 4/9) of hens with ovarian tumors which express mesothelin mRNA and were not found in hens with tumors that did not express mesothelin (n = 0/5) or normal ovaries (n = 0/5). Conclusion The results support the utility of the hen as a novel model for preclinical studies of mesothelin as a biomarker and a target for immunotherapy.
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- 2011
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