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Yan-yun Zhang – One of the best experts on this subject based on the ideXlab platform.
An effective vaccine against colon cancer in mice: use of recombinant adenovirus interleukin-12 transduced dendritic cells.World journal of gastroenterology, 2008Co-Authors: Liang Wang, Yan-yun ZhangAbstract:
AIM: To investigate the effect of a vaccine with recombinant adenovirus interleukin-12 (Advil-12) transduced dendritic cells (DCs) against colon cancer in mice.
METHODS: DCs and Advil-12 were incubated together at different time intervals and at different doses. Supernatant was collected and tested for IL-12 by enzyme-linked immunosorbent assay (ELISA). In order to determine whether tumor cell lysate-pulsed (TP) Advil-12/DCs enhance therapeutic potential in the established tumor model, CT26 colon tumor cells were implanted subcutaneously (s.c.) in the midflank of naive BALB/c mice. Tumor-bearing mice were injected with a vaccination of CT26 TP Advil-12/DCs on d 3 and 10. As a protective colon tumor model, naive BALB/c mice were immunized s.c. in their abdomens with CT26 TP Advil-12/DCs twice at seven day intervals. After the immunization on d 7, the mice were challenged with a lethal dose of CT26 tumor cells and survival times were evaluated. Subsequently, cytotoxic T lymphocyte (CTL) activity and interferon gamma (IFNγ) secretion was evaluated in the immunized mice, and assayed CTL ex vivo.
RESULTS: Murine DCs were retrovirally transduced with Advil-12 efficiency, and the Advil-12 transduced DCs secreted a high level of IL-12 (Advil-12/DCs, 615.27 ± 42.3 pg/mL vs DCs, 46.32 ± 7.29 pg/mL, P < 0.05). Vaccination with CT26 TP Advil-12/DCs could enhance anti-tumor immunity against CT26 colon tumor in murine therapeutic models (tumor volume on d 19: CT26 TP Advil-12/DCs 107 ± 42 mm3 vs CT26 TP DCs 383 ± 65 mm3, P < 0.05) and protective models. Moreover, the CT26 TP Advil-12/DC vaccination enhances tumor-specific CTL activity, producing high levels of IFNγ in immunized mice. Ex vivo primed T cells with Advil-12/DCs were able to induce more effective CTL activity than in primed T cells with CT26 TP/DCs (E:T = 100:1, 69.49% ± 6.11% specific lysis vs 37.44% ± 4.32% specific lysis, P < 0.05). CONCLUSION: Vaccination with recombinant Advil-12 transduced DC pulsed tumor cell lysate enhance anti-tumor immunity specific to colon cancer in mice.
David Kellstein – One of the best experts on this subject based on the ideXlab platform.
Ibuprofen Sodium Is Absorbed Faster than Standard Ibuprofen Tablets: Results of Two Open-Label, Randomized, Crossover Pharmacokinetic StudiesDrugs in R&D, 2014Co-Authors: Thomas J. Legg, Aziz L. Laurent, Rina Leyva, David KellsteinAbstract:
A novel ibuprofen (IBU) formulation, Advil® Film-Coated Tablets (IBUNa), was developed.
ORIGINAL RESEARCH ARTICLE Ibuprofen Sodium Is Absorbed Faster than Standard Ibuprofen Tablets: Results of Two Open-Label, Randomized, Crossover Pharmacokinetic Studies, 2014Co-Authors: Rina Leyva, David KellsteinAbstract:
The Author(s) 2014. This article is published with open access at Springerlink.com Background A novel ibuprofen (IBU) formulation, Advil Film-Coated Tablets (IBUNa), was developed. Objective Pharmacokinetic comparison of IBUNa versus other IBU formulations. Study Design Two randomized, single-dose, open-label, five-way crossover pharmacokinetic studies. Setting Inpatient research clinic. Subjects Seventy-one healthy adult volunteers
Jim Xiang – One of the best experts on this subject based on the ideXlab platform.
OPEN ACCESS, 2014Co-Authors: Via Il–induced Foxp Downregulation, Yufeng Xie, Kalpana Kalyanasundaram Bhanumathy, Bei Zhang, Khawaja Ashfaque Ahmed, Mabood Qureshi, Min Tao, Xin Tan, Jim XiangAbstract:
Abstract: Dendritic cells (DCs), the most potent antigen-presenting cells have been extensively applied in clinical trials for evaluation of antitumor immunity. However, the efficacy of DC-mediated cancer vaccines is still limited as they are unable to sufficiently break the immune tolerance. In this study, we constructed a recombinant adenoviral vector (Advil-6) expressing IL-6, and generated IL-6 transgene-engineered DC vaccine (DCOVA/IL-6) by transfection of murine bone marrow-derived ovalbumin (OVA)-pulsed DCs (DCOVA) with Advil-6. We then assessed DCOVA/IL-6-stimulated cytotoxic T-lymphocyte (CTL) responses and antitumor immunity in OVA-specific animal tumor model. We demonstrate that DCOVA/IL-6 vaccine up-regulates expression of DC maturation markers, secretes transgene-encoded IL-6, and more efficiently stimulates OVA-specific CTL responses an
Enhanced therapeutic efficacy of adenovirus-mediated interleukin-24 gene therapy combined with ionizing radiotherapy for nasopharyngeal carcinomaOncology reports, 2013Co-Authors: Jisheng Liu, Jim Xiang, Yujuan Zhang, Peng Sun, Yufeng Xie, Jicheng YangAbstract:
Melanoma differentiation-associated gene-7 (mda-7)/interleukin-24 (IL-24), a unique cytokine tumor suppressor, displays ubiquitous antitumor activities and cancer-specific cytotoxicities via multiple signaling pathways. In the present study, we investigated the antitumor effect of adenovirus-mediated IL-24 (Advil-24) gene therapy in conjunction with ionizing radiation on CNE-2Z human nasopharyngeal carcinoma (NPC) cells in vitro and in vivo in athymic nude mice, and its potential mechanisms. We demonstrated that Advil-24 gene therapy plus ionizing radiotherapy induced enhanced growth inhibition, cell cycle G1 phase arrest and apoptosis in vitro in CNE-2Z human NPC cells and in vivo in CNE-2Z xenografted tumors subcutaneously implanted in athymic nude mice. Mechanistically, Advil-24 combined with ionizing radiation led to the substantial upregulation of P21 and P27 cyclin-dependent kinase (CDK) inhibitors, ratio of pro-apoptotic to anti-apoptotic molecules Bax/Bcl-2 and cleaved caspase‑3 as well as downregulation of cyclin E and CDK2 in vitro and in vivo in CNE-2Z human NPC cells. Furthermore, Advil-24 plus radiation additively reduced the tumor vessel CD34 expression and microvessel density in vivo. More importantly, Advil-24 potentially blocked the radiation-induced enhancement of vascular endothelial growth factor (VEGF), a pro-angiogenic factor. The enhanced antitumor activity against NPC elicited by Advil-24 gene therapy combined with ionizing radiotherapy was closely associated with the enhanced induction of G1 phase arrest and apoptosis via additive modulation of cell cycle regulatory molecules and activation of intrinsic apoptotic pathways, and the overlapping inhibition of tumor angiogenesis. Thus, our results suggest that Advil-24 gene therapy combined with ionizing radiotherapy may be a novel and effective treatment strategy for human NPC.
Intratumoral coinjection of two adenoviral vectors expressing functional interleukin-18 and inducible protein-10, respectively, synergizes to facilitate regression of established tumorsCancer Gene Therapy, 2002Co-Authors: Yongqing Liu, Hui Huang, Anurag Saxena, Jim XiangAbstract:
We have constructed two recombinant adenoviral vectors AdVIP-10 and Advil-18 expressing the functional chemokine IFN-γ inducible protein (IP)-10 and cytokine interleukin (IL)-18, respectively. Injection of either AdVIP-10 or Advil-18 subcutaneously into tumor nodules derived from the J558 murine myeloma cell line delayed some tumor growth but it was not curative in all cases. Coinjection of these two vectors at the same tumor nodule not only significantly suppressed the tumor growth, but also cured established tumors in 8 of 10 (80% tumor free) mice. The latter treatment stimulated T-cell infiltration into tumors in association with tumor necrosis formation, induced a type 1 immune response and induced the activation of J558 tumor–specific cytotoxic T lymphocytes. Moreover, the antitumor activity of IP-10 and IL-18 combined gene therapy was significantly diminished in mice with depletion of either CD4^+ (50% tumor free) or CD8^+ (40% tumor free) T cells, and completely lost (0% tumor free) in T cell–deficient nude and IFN-γ knockout mice, indicating the critical roles of T cells and IFN-γ in this therapeutical model. Taken together, the findings of this study demonstrate that the combined use of two adenoviral vectors expressing IP-10 and IL-18, respectively, synergize to facilitate regression of established tumors. These observations also suggest the potential use of double-recombinant adenoviral vectors expressing chemokines and immunomodulatory cytokines in cancer gene therapy.