3D Tissue Models

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Peer Reviewed Papers, Books, Chapters

Year Title Citation Authors Review type Summary Keywords File filename File mime type
1. 2009 Flexible needle-tissue interaction modeling with depth-varying mean parameter: K. Yan, T. Podder, Y. Yu, T.I. Liu, C.W.S. Cheng, and W.S. Ng
2. 2009 MRI-guided robot-assisted lumpectomy Yu, Y.; Yan, K.; Podder, T.; Ng, W.S.; Brill, K.; Liao, L
3. 2009 Impact of transrectal ultrasound- and computed tomography-based seed localization on postimplant dosimetry in prostate brachytherapy MS Chew, J Xue, C Houser, V Misic, J Cao, T Cornwell, J Handler, Y Yu, E Gressen.
4. 2009 Needle Steering Modeling Kaiguo Yan; Wan Sing Ng; Keck Voon Ling; Yan Yu; Podder, T.; Liu, T.-I.; and Cheng, C.W.S.
5. 2009 Brachytherapy Needle Insertion: an in Vivo Data Analysis, Podder, T.K., Messing, E.M., Rubens, D.J.Strang, J.G., Clark, D.P., Fuller, D., Sherman, J., Brasacchio, R.A.,Ng, W.S., and Yu, Y
6. 2009 n/a Names of co-authors
7. 2008 Force Prediction and Tracking for Image-guided Robotic System using Neural Network Ivan Buzurovic, Tarun K. Podder, and Yan Yu
8. 2008 Radioactive seed immobilization techniques for interstitial brachytherapy K. Yan, T. Podder, I. Buzurovic, Y. Hu, E. Messing, D. Rubens, A. Dicker, R. Valicenti, N. Sarkar, W. Ng, Y. Yu
9. 2008 prostate stabilization during transperineal LDR brachytherapy Tarun Podder, Jason Sherman, Deborah Rubens, Edward Messing,John Strang,Wan-Sing Ng and Yan Yu
10. 2008 Dynamics-based Decentralized Control of Robotic Couch and Multi-leaf Collimators T.K. Podder, I. Buzurovic, Y. Hu, J.M. Galvin, and Y. Yu
11. 2008 Real-time control strategy for collision avoidance and seed deposition in EUCLIDIAN brachytherapy robotic system”, I. Buzurovic, V. Misic, T. Podder, Y. Hu, K. Yan, R. Valicenti, A. Dicker, Y. Yu, E. Messing, D. Rubens, J. Strang, L. Liao, W.-S. Ng
12. 2008 Acoustic characterization for a multi-modal breast cancer diagnosis and ablation Y. Hu,  T. Podder, K. Yan, I. Buzurovic, B. Winey, L. Liao, K.Parker, Y. Yu
13. 2008 Investigation of Radioactive Seed Immobilization Techniques for Interstitial Brachytherapy Procedure: K. Yan, T. Podder, I. Buzurovic, Y. Hu,  E. Messing,  D. Rubens, A. Dicker,  R. Valicenti, N. Sarkar, W. Ng, Y. Yu,
14. 2008 A Novel Method for Estimating Needle Insertion Force using Patient-specific Factors”, K. Yan, T. Podder, J. Sherman, J. Joseph, L.Li, D. Rubens, E. Messing, J. Huang, L. Liao, P. Okunieff, Y. Yu
15. 2007 Partial transmission high-speed continuous tracking multi-leaf collimator for 4D adaptive radiation therapy Tarun K. Podder, Ivan Buzurovic, Yida Hu, James M. Galvin, and Yan Yu
16. 2007 Sono-contrast spectroscopy for breast cancer detection Y. Yu, Y. Hu, K. Yan, T. Podder, and L. Liao
17. 2007 'Robotic system for prostate brachytherapy', Yu, Y., Podder, T. K., Zhang, Y. D., Ng, W. S., Misic, V., Sherman, J., Fuller, D., Rubens, D. J., Strang, J. G., Brasacchio, R. A. and Messing, E. M. (2007)
18. 2007 Computational methodology for resonant nano-plasma theranostics for cancer treatment. Pradhan A, Yu Y, Nahar S, Silver E, Pitzer R.
19. 2007 Coordinated dynamics-based control of robotic couch and MLC-bank for feedforward radiation therapy. T.K. Podder, I. Buzurovic, and Y. Yu.
20. 2007 Prostate boundary detection Misic V, Sampath V, Yu Y.
21. 2007 Mechanical properties of human prostate tissue in the context of surgical needle insertion. T.K. Podder, J. Sherman, L. Li, J. Joseph, D.R. Rubens, E.M. Messing, J. Huang, Y. Yu.
22. 2007 ’Smart’ Needle for Percutaneous Surgery: Influential Factor Investigation”, K. Yan, T.K. Podder, W.S. Ng, and Y. Yu
23. 2007 Multi-channel robotic system for prostate brachytherapy”, Proc. T.K. Podder, W.S. Ng, and Y. Yu
24. 2007 Hazard analysis of EUCLIDIAN: An image-guided robotic brachytherapy system”, Y. Hu, T.K. Podder, I. Buzurovic, K. Yan, W.S. Ng, and Y. Yu
25. 2006 Dynamic planning in single needle brachytherapy systems. Misic, V., Fu, L., Podder, T.K., Liao, L., Rubens, D.J., Brasacchio, R., Messing, E.M., Strang, J.G., Ng, W.S., Yu, Y.,
26. 2006 Feasibility of mixing angulated and parallel needles in planning prostate Fu, L., Liu, H., Ng, W.S., Rubens, D., Strang, J., Messing, E., Yu, Y., Hybrid dosimetry:
27. 2006 In vivo cancer diagnosis with optical spectroscopy and acoustically induced blood stasis Winey, B.A., Misic, V. , Liao, L. , Parker, K. , Fenton, B., Yu, Y.
28. 2006 In vivo Motion and Force Measurement of Surgical Needle Intervention Podder, T.K., Clark, D.P., Fuller, D., Messing, E. M., Rubens, D. J., Brasacchio, R., Strang, J.G., Sherman, J., Liao, L., Ng, W.S., Yu, Y.
29. 2006 “Image-guided brachytherapy for prostate cancer Rubens DJ, Yu Y, Barnes AS, Strang, JS, Brasacchio R.
30. 2006 A noninvasive optical probe for breast cancer: Winey, B.A., Misic, V., Fenton, B., Liao, L., Parker, K., Yu, Y.,
31. 2006 Seed Localization using TRUS and GRF based Gaussian filters Sampath, V., Misic, V., Saber, E., Liu, H., Yu, Y.
32. 2006 A method to minimize puncture force and organ deformation. Int. J. Podder, T.K., Liao, L., Sherman, J., Fuller, D., Misic, V., Rubens, D.J., Messing, E.M., Strang, J.G., Ng, W.S., Yu, Y.
33. 2006 A novel multi-modality image-guided US-NIR scanner for breast cancer diagnosis Winey, B.A., Liao, L., Zhang, Y.D., Helbig, J., Misic, V., Parker, K., Podder, T., Yu, Y.
34. 2006 Robot-assisted platform for intratumoral delivery (RAPID). Yu, Y., Podder, T.K., Zhang, Y.D., Ng, W.S., Misic, V., Fu, L., Sherman, J., Fuller, D., Messing, E.M., Rubens, D.J., Strang, J.G., Brasacchio, R.A.
35. 2006 Needle Insertion Force Estimation Podder, T.K., Sherman, J., Fuller, D., Messing, E.M., Rubens, D.J., Strang, J.G., Brasacchio, R.A., and Yu, Y.
36. 2006 Efficacy of Prostate Stabilizing Techniques during Brachytherapy Sherman, J., Podder, T.K., Fu, L., Misic, V., Fuller, D., Winey, B., Messing, E.M., Rubens, D.J., Strang, J.G., Brasacchio, R.A., and Yu, Y.
37. 2006 Oximetry considerations in the small source detector separation limit. Winey, B. A., Yu. Y.,
38. 2006 Surgical Needle Intervention in Soft Tissue: Podder, T.K., Sherman, J., Fuller, D., Messing, E.M., Rubens, D.J., Strang, J.G., Brasacchio, R.A., and Yu, Y.
39. 2006 Robot-Assisted Prostate Brachytherapy. Yu, Y., Podder, T., Zhang, Y., Ng, W.S., Misic, V., Sherman J., Fu L., Fuller, D., Messing, E., Rubens, D., Strang, J., and Brasacchio R.
40. 2006 Online parameter estimation for surgical needle steering model. Yan, K.G., Podder, T., Xiao, D., Yu, Y., Liu, T.I., Ling, K.K., and Ng, W.S.
41. 2005 In vivo Optical Spectroscopy of Acoustically Induced Blood Stasis Winey, B.A., Misic, V., Fenton, B., S. Paoni, Liao, L., Okunieff, P., Liu, H., K.J. Parker, Yu, Y.,
42. 2005 A novel approach for reducing target movement during percutaneous surgery Yan, K., Ng, W.S., Ling, K.V., Yan Yu, Podder, T.
43. 2005 Effects of Velocity Modulation during Surgical Needle Insertion Podder, T.K., Clark, D.P., Fuller, D., Sherman, J., Ng, W.S., Liao, L., Rubens, D.J.Strang, J.G., Messing, E.M., Zhang, Y.D., and Yu, Y.,
44. 2005 Assessment of Prostate Brachytherapy and Breast Biopsy Needle Insertions Podder, T.K., Liao, L., Sherman, J., Misic, V., Zhang, Y.D., Fuller, D., Rubens, D.J., Messing, E.M., Strang, J.G., Ng, W.S., Yu, Y.,
45. 2005 Robotic Needle Insertion in Soft Material Phantoms: Podder, T.K., Clark, D.P., Sherman, J., Fuller, D., Rubens, D.J. Ng, W.S., Messing, E.M., O’Dell, W., Strang, J.G., Zhang, Y.D., and Yu, Y.,
46. 2005 Effects of Tip Geometry of Surgical Needles: Podder, T.K., Clark, D.P., Sherman, J., Fuller, D., Messing, E.M., Rubens, D.J.,Strang, J.G., Zhang, Y.D., O’Dell, W., Ng, W.S., Yu, Y.
47. 2005 Method to Reduce Force and Target Movement during Surgical Needle Interventions Podder, T.K., Sherman, J., Clark, D.P., Fuller, D., Rubens, D.J.Messing, E.M., Strang, J.G., Liao, L., Ng, W.S., and Yu, Y.
48. 2005 Tumor Detection in vivo with Optical Spectroscopy Misic, V., Winey, B.A., Fenton, B., S. Paoni, Liao, L., Okunieff, P., Liu, H., K.J. Parker, Yu, Y.
49. 2005 High frequency translational oscillation Yan, K., Ng, W.S., Ling, K.V., Liu, T.I., Yu, Y., Podder, T. (2005).
50. 2005 Effects of Coating on Friction Force during Needle Insertion Podder, T., Clark, D., Fuller, D., Sherman, J., Messing, E., Rubens, D., Strang, J., Ng, W.S., Yu, Y.,
51. 2005 Evaluation of Robotic Needle Insertion Podder, T.K., Sherman, J., Clark, D.P., Messing, E.M., Rubens, D.J., Strang, J.G., Liao, L., Brasacchio, R.A., Zhang, Y., Ng, W.S., Yu, Y.,
52. 2004 Preliminary work of a smart needling project, Yan, K., Liu, T.I, Ling, K. V., Yu, Y., O’Dell, W., Sing, N.W.
53. 2004 Literature Review on Needle Guidance in Soft Tissue Yan, K., Liu, T.I., Ling, K.V., Yu, Y., O’Dell, W., Ng, W.S.,
54. 2004 Genetic algorithm-based dynamic intraoperative treatment Fu, L., Yu, Y., Liu, H.
55. 2004 Bouquet brachytherapy: Fu, L., Ng, W.S., Liu, H., O'Dell, W. , Rubens, D., Strang, J., Schell, M.C., Brasacchio, R., Liao, L., Messing, E., Yu, Y.,
56. 2003 Automatic localization of implanted seeds from postimplant CT images. Liu, H., Cheng, G., Yu, Y., Brasacchio, R., Rubens, D., Strang, J., Liao, L., Messing, E.
57. 2003 Automatic segmentation of prostate boundaries in transrectal ultrasound Liu, H., Cheng, G., Rubens, D., Strang, J., Liao, L., R. Brasacchio, R., Messing, E., Yu, Y.
58. 2003 Feasibility test of prospective tracking of respiratory signals Liu, H., Yu, Y., Schell, M., O’Dell, W., Okunieff, P.
59. 2002 Automatic segmentation of prostate boundaries in transrectal ultrasound Liu, H., Cheng, G., Rubens, D., Strang, J., Liao, L., Brasacchio, R., Messing, E., Yu, Y.,
60. 2001 Intraoperative planning and evaluation of permanent prostate brachytherapy: Nag, S., Ciezki, J.P., Cormack, R., Doggett, S., DeWyngaert, K., Edmundson, G. K., Stock, R. G., Stone, N., Yu, Y, Zelefsky, M.
61. 2001 Real-time US versus CT determination of pubic arch interference for brachytherapy Strang, J., Rubens, D.J., Brasacchio, R.A., Yu, Y.,
62. 2001 Dynamic Brachytherapy of the Prostate under Active Image Guidance. Cheng, G., Liu, H., Liao, L., Yu, Y.,
63. 2000 Towards a statistically relevant endpoint for prostate seed implants. Rosenzweig, D., Yu, Y.
64. 2000 Multi-objective optimization in radiotherapy: Yu, Y., Zhang, JB, Cheng, G., Schell, M.C., Okunieff, P.
65. 2000 Innovation and challenges to intravascular brachytherapy. Cardiovasc. Schell, M.C., Yu, Y.,
66. 2000 The American Brachytherapy Society recommendations for permanent prostate brachytherapy postimplant dosimetric analysis. Nag, S., Bice, W., DeWyngaert, K., Prestidge, B., Stock, R., Yu, Y.,
67. 1999 Intraoperative optimized inverse planning for prostate brachytherapy: Messing, E.M., Zhang, JB Y., Rubens, D.J., Brasacchio, R.A., Strang, J.G., Soni, A., Okunieff, P.G., Yu, Y.,
68. 1999 Circumventing the learning curve of dose and volume in intravascular brachytherapy Yu, Y., Schell, M.C., Rubin, P.
69. 1999 Permanent prostate seed implant brachytherapy: Yu, Y., (Chair), Anderson, L.L., Li, Z., Mellenberg, D.E., Nath, R., Schell, M.C., Waterman, F.M., Wu, A., Blasko, J.C.
70. 1998 MR image-guided portal verification for brain treatment field. Yin, F-F., Gao, Q., Xie, H., Nelson, D.F., Yu, Y., Kwok, W.E, Totterman, S., Schell, M.C., Rubin, P.
71. 1998 Automated treatment planning engine for prostate seed implant Yu, Y., Zhang, JB Y., Brasacchio, R.A., Okunieff, P.G., Rubens, D.J., Strang, J.G., Soni, A.,
72. 1997 Decision theoretic optimization of radiotherapy planning Yu, Y., Zhang, JB Y., Schell, M. C.
73. 1997 Conformal radiotherapy of small intracranial lesions Schell, M. C., Rosenzweig, D. P., Yu, Y.,
74. 1997 Differential dose delivery using a non-docking applicator for intraoperative Huq, M. S., Yu, Y., Mohiuddin, M., Ahmad, N., Suntharalingam, N.
75. 1997 Multi-objective decision theory for computational optimization in radiation Yu, Y.
76. 1997 Decision-theoretic steering and genetic algorithm optimization: Yu, Y., Schell, M.C., Zhang, J.B. Y.
77. 1997 Multi-objective stochastic reasoning and genetic algorithm optimization: Yu, Y., Zhang, JB Y., Schell, M.C.
78. 1996 Limitations of the minimum peripheral dose as a parameter for dose Yu, Y.
79. 1996 Limitations of the minimum peripheral dose as a parameter for dose Yu, Y., Waterman, F.M., Suntharalingam, N., Schulsinger, A
80. 1996 A genetic algorithm for the optimization of prostate implants Yu, Y., Schell, M.C.
81. 1995 Dosimetric characteristics of a commercial multileaf collimator Huq, M.S., Yu, Y., Chen, Z.P., Suntharalingam, N.
82. 1994 Opacities for stellar envelopes. Seaton, M.J., Yu, Y., Mihalas, D., Pradhan, A.K.
83. 1992 The Opacity Project Yu, Y.
84. 1992 The Opacity Project: Opacities. Presented at XXI I.A.U. General Assembly, Yu, Y.
85. 1990 The Opacity Project: Yu, Y.,
86. 1989 Atomic data for opacity calculations: Luo, D., Pradhan, A.K., Saraph, H.E., Storey, P.J., Yu, Y
87. 1987 Atomic data for opacity calculations: III. Yu, Y., Taylor, K.T.
88. 1987 Atomic data for opacity calculations: II. Berrington, K.A., Burke, P.G., Butler, K., Seaton, M.J., Storey, P.J., Taylor, K.T., Yu, Y
89. 1987 Photoionisation cross-sections for C ii. Yu, Y., Seaton, M.J
90. 1985 R-matrix theory of the hydrogen atom Yu, Y., Seaton, M. J
91. Obesity and elevated circulating cholesterol are risk factors for breast cancer recurrence, while the use of statins, cholesterol biosynthesis inhibitors widely used for treating hypercholesterolemia, is associated with improved disease-free survival. Pubmed Obesity and elevated circulating cholesterol are risk factors for breast cancer recurrence, while the use of statins, cholesterol biosynthesis inhibitors widely used for treating hypercholesterolemia, is associated with improved disease-free survival. Here, we show that cholesterol mediates the metastatic effects of a high-fat diet via its oxysterol metabolite, 27-hydroxycholesterol. Ablation or inhibition of CYP27A1, the enzyme responsible for the rate-limiting step in 27-hydroxycholesterol biosynthesis, significantly reduces metastasis in relevant animal models of cancer. The robust effects of 27-hydroxycholesterol on metastasis requires myeloid immune cell function, and it was found that this oxysterol increases the number of polymorphonuclear-neutrophils and γδ-T cells at distal metastatic sites. The pro-metastatic actions of 27-hydroxycholesterol requires both polymorphonuclear-neutrophils and γδ-T cells, and 27-hydroxycholesterol treatment results in a decreased number of cytotoxic CD8+T lymphocytes. Therefore, through its actions on γδ-T cells and polymorphonuclear-neutrophils, 27-hydroxycholesterol functions as a biochemical mediator of the metastatic effects of hypercholesterolemia.High cholesterol is a risk factor for breast cancer recurrence. Here the authors show that cholesterol promotes breast cancer metastasis via its metabolite 27-hydroxycholesterol (27HC) that acts on immune myeloid cells residing at the distal metastatic sites, thus promoting an immune suppressive environment.
92. Osteosarcoma (OS) is the most common primary malignant bone tumor in childhood and adolescence with poor prognosis. Pubmed Osteosarcoma (OS) is the most common primary malignant bone tumor in childhood and adolescence with poor prognosis. The mechanism underlying tumorigenesis and development of OS is largely unknown. ALDH1B1 has been reported to involve in many kinds of human cancers and functions as an oncogene, but the role of ALDH1B1 in OS has not been investigated comprehensively. In the present study, we aimed to examine clinical value and biological function of ALDH1B1 in OS. Firstly, we investigated the roles of ALDH1B1 on an OS tissue microarray (TMA) as well as two OS cohorts from GEO database. We found that ALDH1B1 was significantly up-regulated in OS tissues and was independently associated with poor prognosis. Moreover, ALDH1B1 silencing could suppress the proliferation, migration, invasion in vitro and inhibit the growth of xenograft tumor and of OS cells in vivo. Additional, ALDH1B1 knockdown increased the apoptosis rate and lead to cell cycle arrest in G1 stage of OS cell in vitro. More importantly, the inhibition of ALDH1B1 expression could increase the sensitivity of OS cells to chemotherapy, which suggested that ALDH1B1 might be served as a therapeutic target to reverse drug resistance in chemotherapy in OS patients. Taken together, our founding suggested that ALDH1B1 contributes to OS tumor progression and drug resistance, which may represent a novel prognostic marker and potential therapeutic target for OS patients. ALDH1B1; metastasis; osteosarcoma; progression; proliferation
93. Cervical cancer, the third most commonly occurring cancer, is the second leading cause of cancer related mortality among women. Pubmed Cervical cancer, the third most commonly occurring cancer, is the second leading cause of cancer related mortality among women. Aberrant ubiquitination and proteasome activity, both human papillomavirus and tumor derived, have been shown to contribute to tumor angiogenesis, proliferation, and invasion in many cancers, including cervical cancer. Thus, small molecule proteasome inhibitors are a potential and strategic treatment option for cervical cancer. In this study, novel proteasome inhibitor delanzomib (CEP-18770) exhibited potent pro-apoptotic and cytotoxic effects on a panel of cervical cancer cell lines by blocking proteasomal activity. Delanzomib also significantly sensitized cervical cancer cells to treatment of doxorubicin (Dox), a traditional chemotherapeutic agent. Furthermore, proteasome inhibition revealed stabilization of p53 and p53 transcriptional targets and induction of p38/JNK phosphorylation. Additionally, delanzomib worked synergistically with Dox to further upregulate p53 and its downstream targets and enhanced Dox-induced p38 phosphorylation. Our study strongly supports the 26S proteasome as a potential therapeutic target in cervical cancer and proteasome inhibition by delanzomib may be a potential treatment strategy for cervical cancer patients. cervical cancer; delanzomib; doxorubicin; p53; proteasome
94. In the course of isolating the attenuated Japanese encephalitis vaccine SA14-14-2, two attenuated strains SA14-9-7 and SA14-5-3 were also obtained that elicited low antibody responses in humans (<10% and 62%, respectively) and exerted much weaker immune protection in animal challenge experiments. Pubmed In the course of isolating the attenuated Japanese encephalitis vaccine SA14-14-2, two attenuated strains SA14-9-7 and SA14-5-3 were also obtained that elicited low antibody responses in humans (<10% and 62%, respectively) and exerted much weaker immune protection in animal challenge experiments. However, the reason for these differences remains unknown. In order to understand why SA14-14-2 is superior to SA14-9-7 and SA14-5-3, we employed a reverse genetics method to identify the key mutations in the virus genome that determine the immunogenicity of live attenuated Japanese encephalitis viruses. We first sequenced the full genomic sequences of SA14-9-7 and SA14-5-3 and found mutations that changed four amino-acid base pairs when compared to the envelope gene of SA14-14-2. We mutated the genome of SA14-14-2 to generate these mutations both singly (E-177, E-264, E-279 and E-315) and in combination (E-177/264, E-279/315 and E-177/264/279/315) and tested these mutants along with parental strains SA14-14-2, SA14-9-7 and SA14-5-3 for their immunogenicity in vivo. When mice were immunized with SA14-9-7 and SA14-5-3, lower levels of neutralizing antibodies were generated compared with the immune response to SA14-14-2. Furthermore, SA14-5-3 was more immunogenic than SA14-9-7, which replicated the results previously seen in humans. Point mutations E-177, E-264, E-279 and E-315 diminished the immunogenicity of SA14-14-2 with E-264 and E-315, contributing the most to this phenotype. The mutant rJEV (E-177/E-264/E-279/E-315) containing all four point mutations exhibited the lowest immunogenicity with a seroconversion rate of 0 at an inoculation dose of 103 PFU (plaque-forming unit). We have identified the key amino acids in the envelope protein that account for the superior immunogenicity of SA14-14-2.
95. Breast cancer is one of the most common causes of cancer related deaths in women. Pubmed Breast cancer is one of the most common causes of cancer related deaths in women. Currently, with the development of early detection, increased social awareness and kinds of treatment options, survival rate has improved in nearly every type of breast cancer patients. However, about one third patients still have increased chances of recurrence within five years and the five-year relative survival rate in patients with metastasis is less than 30%. Breast cancer contains multiple subtypes. Each subtype could cause distinct clinical outcomes and systemic interventions. Thereby, new targeted therapies are of particular importance to solve this major clinical problem. Aptamers, often termed "chemical antibodies", are functionally similar to antibodies and have demonstrated their superiority of recognizing target with high selectivity, affinity and stability. With these intrinsic properties, aptamers have been widely studied in cancer biology and some are in clinical trials. In this review, we will firstly discuss about the global impacts and mechanisms of breast cancer, then briefly highlight applications of aptamers that have been developed for breast cancer and finally summarize various challenges in clinical translation of aptamers. SELEX; aptamer; breast cancer; diagnosis; targeted therapy
96. The in vitro activation of T cells by synthetic particles is a promising technique for adoptive cancer immunotherapy. Pubmed The in vitro activation of T cells by synthetic particles is a promising technique for adoptive cancer immunotherapy. While it is known that cell-surface receptors form clusters during T cell activation, the use of clustered ligands on synthetic particles to modulate T cell response is a largely unexplored concept. Building upon our previous finding that T cells respond differently to various micro-sized patterns of ligands, we here investigate the effect of nano-sized ligand clusters on T cell activation. Two-faced Janus nanoparticles were fabricated to display ligands of different functions in spatially segregated clusters on single nanoparticles. Going beyond our earlier qualitative study, here we precisely quantified and controlled the surface density and the total amount of ligands on single nanoparticles. We show that nanoparticles with clustered ligands activate T cells to a greater level than ones uniformly coated with the same number of ligands. The enhanced effect is due to increased local surface density of ligands. The results demonstrate that the spatial arrangement of ligands on particles influences activation response of T cells and may be used as a new strategy to increase T cell stimulation in the presence of insufficient amount of stimuli. This fundamental study also represents an initial step in using nanoscale Janus particles for manipulating immune cell responses.
97. Rationale: Nasopharyngeal carcinoma (NPC) is the most frequent head and neck tumor in South China. Pubmed Rationale: Nasopharyngeal carcinoma (NPC) is the most frequent head and neck tumor in South China. The presence of cancer stem cells (CSCs) in NPC contributes to tumor maintenance and therapeutic resistance, while the ability of CSCs to escape from the apoptosis pathway may render them the resistant property to the therapies. Inhibitor of apoptosis proteins family proteins (IAPs), which are overexpressed in nasopharyngeal carcinoma stem cells, may play an important role in maintaining nasopharyngeal cancer stem cell properties. Here, we develop a novel CSC-targeting strategy to treat NPC through inhibiting IAPs. Methods: Human NPC S-18 and S-26 cell lines were used as the model system in vitro and in vivo. Fluorescence activated cell sorting (FACS) assay was used to detect nasopharyngeal SP cells and CD44+ cells. The characteristics of CSCs were defined by sphere suspension culture, colony formation assay and cell migration. The role of XIAP on the regulation of Sox2 protein stability and ERK1-mediated phosphorylation of Sox2 signaling pathway were analyzed using immunoblotting, immunoprecipitation, immunofluorescence, phosphorylation mass spectrometry, siRNA silencing and plasmid overexpression. The correlation between XIAP and Sox2 in NPC biopsies and their role in prognosis was performed by immunohistochemistry. APG-1387 or chemotherapies-induced cell death and apoptosis in S-18 and S-26 were determined by WST, immunoblotting and flow cytometry assay. Results: IAPs, especially X chromosome-linked IAP (XIAP), were elevated in CSCs of NPC, and these proteins were critically involved in the maintenance of CSCs properties by enhancing the stability of Sox2. Mechanistically, ERK1 kinase promoted autophagic degradation of Sox2 via phosphorylation of Sox2 at Ser251 and further SUMOylation of Sox2 at Lys245 in non-CSCs. However, XIAP blocked autophagic degradation of Sox2 by inhibiting ERK1 activation in CSCs. Additionally, XIAP was positively correlated with Sox2 expression in NPC tissues, which were associated with NPC progression. Finally, we discovered that a novel antagonist of IAPs, APG-1387, exerted antitumor effect on CSCs. Also, the combination of APG-1387 with CDDP /5-FU has a synergistic effect on NPC. Conclusion: Our study highlights the importance of IAPs in the maintenance of CSCs in NPC. Thus, XIAP is a promising therapeutic target in CSCs and suggests that NPC patients may benefit from a combination treatment of APG-1387 with conventional chemotherapy. SMAC mimetics; Sox2; XIAP; cancer stem-cells; nasopharyngeal cancer
98. The aim of the present study was to investigate whether niclosamide could sensitize the nasopharyngeal carcinoma cells to radiation and further explore the underlying mechanisms. Pubmed The aim of the present study was to investigate whether niclosamide could sensitize the nasopharyngeal carcinoma cells to radiation and further explore the underlying mechanisms. CCK-8 assay was used to determine the effect of niclosamide on the proliferation of NPC cells. Colony formation assay was used to evaluate the radiosensitizing effect of niclosamide on NPC cells. Flow cytometry analysis was used to determine the apoptosis of NPC cells induced by niclosamide. Immunofluorescent staining was used to detect the formation of γ-H2AX foci and the localization of Ku70/80 proteins in NPC cells. Real-time PCR quantification analysis was used to examine the level of Ku70/80 mRNA. DNA damage repair-related proteins were detected by western blot analysis. Our results showed that niclosamide markedly suppressed the proliferation of NPC cells. Niclosamide pretreatment followed by irradiation reduced the colony forming ability of NPC cells. Niclosamide in combination with irradiation significantly increased the apoptotic rate of NPC cells. Niclosamide significantly reduced the transcriptional level of K70/80 but not the translocation of Ku70/80 protein induced by irradiation. In conclusion, our study demonstrated that niclosamide could inhibit the growth of NPC cells and sensitize the NPC cells to radiation via suppressing the transcription of Ku70/80. DNA damage repair; Ku70/80; nasopharyngeal carcinoma; niclosamide; radiosensitization
99. APOBEC enzymes are responsible for a mutation signature (TCW>T/G) implicated in a wide variety of tumors. Pubmed APOBEC enzymes are responsible for a mutation signature (TCW>T/G) implicated in a wide variety of tumors. We explore the APOBEC mutational signature in bladder cancer and the relationship with specific mutations, molecular subtype, gene expression, and survival using sequencing data from The Cancer Genome Atlas (n = 395), Beijing Genomics Institute (n = 99), and Cancer Cell Line Encyclopedia. Tumors were split into "APOBEC-high" and "APOBEC-low" based on APOBEC enrichment. Patients with APOBEC-high tumors have better overall survival compared to those with APOBEC-low tumors (38.2 vs. 18.5 months, p = 0.005). APOBEC-high tumors are more likely to have mutations in DNA damage response genes (TP53, ATR, BRCA2) and chromatin regulatory genes (ARID1A, MLL, MLL3), while APOBEC-low tumors are more likely to have mutations in FGFR3 and KRAS. APOBEC3A and APOBEC3B expression correlates with mutation burden, regardless of bladder tumor molecular subtype. APOBEC mutagenesis is associated with increased expression of immune signatures, including interferon signaling, and expression of APOBEC3B is increased after stimulation of APOBEC-high bladder cancer cell lines with IFNγ. In summary, APOBEC-high tumors are more likely to have mutations in DNA damage response and chromatin regulatory genes, potentially providing more substrate for APOBEC enzymes, leading to a hypermutational phenotype and the subsequent enhanced immune response. APOBEC deaminases; DNA damage; interferon; mutagenesis; urinary bladder neoplasms
100. Breast cancer is the most common female cancer with considerable metastatic potential, explaining the need for new candidates that inhibit tumor metastasis. Pubmed Breast cancer is the most common female cancer with considerable metastatic potential, explaining the need for new candidates that inhibit tumor metastasis. In our study, betulinic acid (BA), a kind of pentacyclic triterpenoid compound derived from birch trees, was evaluated for its anti-metastasis activity in vitro and in vivo. BA decreased the viability of three breast cancer cell lines and markedly impaired cell migration and invasion. In addition, BA could inhibit the activation of stat3 and FAK which resulted in a reduction of matrix metalloproteinases (MMPs), and increase of the MMPs inhibitor (TIMP-2) expression. Moreover, in our animal experiment, intraperitoneal administration of 10 mg/kg/day BA suppressed 4T1 tumor growth and blocked formation of pulmonary metastases without obvious side effects. Furthermore, histological and immunohistochemical analyses showed a decrease in MMP-9 positive cells, MMP-2 positive cells and Ki-67 positive cells and an increase in cleaved caspase-3 positive cells upon BA administration. Notably, BA reduced the number of myeloid-derived suppressor cells (MDSCs) in the lungs and tumors. Interestingly, in our caudal vein model, BA also obviously suppressed 4T1 tumor pulmonary metastases. These findings suggested that BA might be a potential agent for inhibiting the growth and metastasis of breast cancer. MDSCs; betulinic acid; breast cancer; migration and invasion; pulmonary metastases


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