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Total 151 results found since Jan 2013.
Abstract B60: Targeting the polyamine addiction of pancreatic cancers: Combination therapies and biomarkers
This project developed a combination therapy which inhibits both polyamine transport and biosynthesis in an effort to target the polyamine addiction of pancreatic cancers. Several parameters were measured in six human pancreatic cell lines (L3.6pl, Panc-1, BxPC3, AsPC-1, Capan-1 and HPNE) and one murine line (Pan02). These included the kinetics of 3H-spermidine uptake (Vmax and Km values), the 72h IC50 value for difluoromethylornithine (DFMO, an inhibitor of polyamine biosynthesis), and the ability of exogenous spermidine to rescue the viability of DFMO-treated cells. DFMO has a mixed clinical history and cancers often esc...
Source: Cancer Research - December 13, 2016 Category: Cancer & Oncology Authors: Otto Phanstiel IV, Meenu Madan, Arjun Patel, Kristen Skruber, Deborah A. Altomare Tags: Molecular Drivers of Pancreatic Cancer Biology and Metastasis Source Type: research
Abstract A67: TFF (Trefoil Factor Family) is a novel tumor suppressor and can be the therapeutic target for pancreatic cancer
Conclusion: TFF1 and TFF2 act as tumor suppressor in pancreatic carcinogenesis in a different manner, and they can be a novel therapeutic target for PDAC.Citation Format: Junpei Yamaguchi, Yukihiro Yokoyama, Toshio Kokuryo, Masato Nagino.{Authors}. TFF (Trefoil Factor Family) is a novel tumor suppressor and can be the therapeutic target for pancreatic cancer. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2016 May 12-15; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(24 Suppl):Abstract nr A67.
Source: Cancer Research - December 13, 2016 Category: Cancer & Oncology Authors: Junpei Yamaguchi, Yukihiro Yokoyama, Toshio Kokuryo, Masato Nagino Tags: Early Detection Source Type: research
LSC Abstract - Activation of FGF9 and 18 in idiopathic pulmonary fibrosis promote survival and migration and inhibit myofibroblast differentiation of human lung fibroblasts
Key developmental lung signaling pathways are reactivated in IPF. FGF9 and FGF18 are involved in epithelial–mesenchymal interactions and are critical for lung development.We evaluated the expression of FGF9, FGF18 and FGFR in lung tissue from controls and IPF patients and assessed their effect on proliferation, survival, migration and differentiation of control and IPF human lung fibroblasts (HLF).HLF were cultured with FGF9 and FGF18. FAS-ligand induced apoptosis was assayed by measuring cleaved-PARP expression. Expression of FGFR mRNA, α-smooth muscle actin, collagen I and MMPs was analyzed with qPCR, western...
Source: European Respiratory Journal - November 7, 2016 Category: Respiratory Medicine Authors: Joannes, A., Jaillet, M., Mailleux, A., Crestani, B. Tags: 3.3 Mechanisms of Lung Injury and Repair Source Type: research
LSC Abstract - Histone deacetylase 7 mediated metabolic remodeling: A new crosslink between pulmonary hypertension and cancer
Pulmonary arterial smooth muscle cells (PASMCs) from Pulmonary Hypertension (PH) patients and several PH animal models are characterized by suppressed mitochondria-dependent apoptosis and hyperpolarization. Similarly to lung cancer (LC) cells, PH-PASMCs have reduced glucose oxidation and increased cytoplasmic glycolysis. Protein acetylation and its enzymes such as histone deacetylases (HDACs) may play a role in the control of metabolism.We assessed the regulation of Class IIa HDACs (HDAC4, 5, 7 and 9) in human and experimental models of PH and lung cancer. By using primary culture of healthy (control-PASMCs), idiopathic de...
Source: European Respiratory Journal - November 7, 2016 Category: Respiratory Medicine Authors: Gamen, E., Chelladurai, P., Grimminger, F., Savai, R., Seeger, W., Savai Pullamsetti, S. Tags: ERS Lung Science Conference 2016 Source Type: research
LSC Abstract - Activation of FGF9 and 18 in idiopathic pulmonary fibrosis promote survival and migration and inhibit myofibroblast differentiation of human lung fibroblasts
Key developmental lung signaling pathways are reactivated in IPF. FGF9 and FGF18 are involved in epithelial–mesenchymal interactions and are critical for lung development.We evaluated the expression of FGF9, FGF18 and FGFR in lung tissue from controls and IPF patients and assessed their effect on proliferation, survival, migration and differentiation of control and IPF human lung fibroblasts (HLF).HLF were cultured with FGF9 and FGF18. FAS-ligand induced apoptosis was assayed by measuring cleaved-PARP expression. Expression of FGFR mRNA, α-smooth muscle actin, collagen I and MMPs was analyzed with qPCR, western...
Source: European Respiratory Journal - November 7, 2016 Category: Respiratory Medicine Authors: Joannes, A., Jaillet, M., Mailleux, A., Crestani, B. Tags: ERS Lung Science Conference 2016 Source Type: research
Is glutamate dehydrogenase in astrocytes one of the keys to control brain glutamate homeostasis?
SummaryBrain glutamate concentration needs to be balanced to avoid excitoxicity. Following glutamatergic neurotransmission astrocytes are responsible for clearance of the synaptic cleft via glutamate transporters. In the astrocyte the conversion of glutamate to glutamine is an essential part of the glutamate‐glutamine cycle. But, a substantial amount of glutamate is oxidatively metabolized in the mitochondria, which to a large extent may be dependent on glutamate dehydrogenase (GDH). Thus, astrocytes are likely the main regulator of the brain glutamate concentration, but how do they do it? We have investigated the role o...
Source: Acta Ophthalmologica - September 13, 2016 Category: Opthalmology Authors: H. Waagepetersen Tags: Abstracts from the 2016 European Association for Vision and Eye Research Conference Source Type: research
Regulating gene expression towards solving ocular surface diseases
SummaryTreatment of genetic eye disease poses significant medical and surgical challenges. We used a bioluminescent corneal reporter gene mouse model to assess efficacy and potency of a number of gene therapy approaches for corneal dystrophy. Various modalities were assessed for delivery of short interfering RNA (siRNA) targeting one of five mutant alleles present in the corneal bioluminescent mouse model enabling assessment of topical, subconjunctival and intrastromal delivery. Potent and sustained in vivo gene silencing >50% for up to 7 days was observed. This siRNA therapy only provides a transient silencing of the ...
Source: Acta Ophthalmologica - September 13, 2016 Category: Opthalmology Authors: T. Moore, S. Atkinson, E. Maurizi, D. Schiroli, L. Mairs, K. Christie, I. McLean, E. Allen, D.L. Pedrioli, J. Moore, A. Nesbit Tags: Abstracts from the 2016 European Association for Vision and Eye Research Conference Source Type: research
In vitro evaluation of anti HSV ‐1 siRNAs and in vivo evaluation of electroporation to transfect siRNAs on murine cornea
ConclusionsThese results demonstrate that siRNA directed against HSV‐1 DNA polymerase efficiently inhibits HSV‐1 replication, suggesting that siRNA based antiviral strategy may be a potential therapeutic alternative to treat HSK. Besides, intracorneal penetration may be facilitated by electroporation.
Source: Acta Ophthalmologica - September 13, 2016 Category: Opthalmology Authors: A. Rousseau, V. Escriou, P. Roy, N. Poccardi, J. Takissian, P. Bigey, M. Labetoulle Tags: Abstracts from the 2016 European Association for Vision and Eye Research Conference Source Type: research
Cytoprotective alpha crystallins in the regulation of RPE cell proteostasis
SummaryAlphaB‐Crystallin (αBC) is an ubiquitous protein with dual function as a molecular chaperone to preserve proteostasis and as an anti‐apoptotic agent. We studied the regulatory role of αBC in murine models of oxygen‐induced retinopathy (OIR), laser‐induced choroidal neovascularization (CNV) and subretinal fibrosis (SF). αBC KO attenuated retinal NV in OIR as compared to WT. In the laser model, CNV lesion size was significantly reduced in αBC KO vs. WT mice. VEGF increased 8 fold in WT vs. αBC KO on day 3 and 7 post‐laser and VEGF secretion was lower in αBC KO vs. WT. Increased mono (tetra)‐ubiquitin...
Source: Acta Ophthalmologica - September 13, 2016 Category: Opthalmology Authors: R. Kannan Tags: Abstracts from the 2016 European Association for Vision and Eye Research Conference Source Type: research
Abstract C42: DNA methyltransferase 1 (Dnmt1) is a key regulator of TGF{beta}-mediated endothelial-to-mesenchymal transition
Cancer-associated fibroblasts (CAFs) are prominent in the tumor microenvironment and they fuel tumor angiogenesis, tumor growth, and metastasis. CAFs are identified by smooth muscle actin and type collagen 1 expression, they promote intratumoral desmoplasia and fibrosis, and they are derived from multiple cellular precursors including tumor endothelial cells (TECs) through a TGFβ-regulated process termed endothelial-to-mesenchymal transition (EndMT). Recently, we uncovered two distinct TEC populations: TGFβ-responders that undergo rapid EndMT accompanied by CAF marker up-regulation in response to TGFβ and TGFβ non-resp...
Source: Cancer Research - July 27, 2016 Category: Cancer & Oncology Authors: Xiao, L., Dudley, A. C. Tags: Tumor Microenvironment Heterogeneity Source Type: research
Abstract B05: N-Myc downstream regulated gene 2 is a novel regulator of lipid metabolism and ubiquitin-proteasome system in cancer
Conclusion: We demonstrated for the first time that NDRG2 is a critical regulator of lipid metabolism and proteasome activity. NDRG2 inhibits the proteasome activity probably by interacting with Nrf1 and promoting its downregulation.Note: This abstract was not presented at the conference.Citation Format: Libo Yao, Xia Li, Xiping Liu, Yi Ru, Mei Zhang. N-Myc downstream regulated gene 2 is a novel regulator of lipid metabolism and ubiquitin-proteasome system in cancer. [abstract]. In: Proceedings of the AACR Special Conference: Function of Tumor Microenvironment in Cancer Progression; 2016 Jan 7–10; San Diego, CA. Philadel...
Source: Cancer Research - July 27, 2016 Category: Cancer & Oncology Authors: Yao, L., Li, X., Liu, X., Ru, Y., Zhang, M. Tags: Metabolism and Tumor Microenvironment Source Type: research
Abstract C05: Pulmonary laminin 332 in tumor cell migration and breast cancer survival
Metastasis to the lung often leads to the demise of the patient, thus a greater understanding of the process might lead to strategies for better cancer control. Tumor cell metastatic ability is determined by both intrinsic properties of tumor cells and contributions from the microenvironment. The goal of this study was to determine the role of the extracellular matrix protein laminin 332 (LN332) in breast cancer progression. Because tumor cell motility is a requirement for metastasis, we hypothesize that lung tissue harbors substances that induce tumor cell migration. In order to better characterize the interaction of brea...
Source: Cancer Research - July 27, 2016 Category: Cancer & Oncology Authors: Carpenter, P. M., Sivadas, P., Ziogas, A., Anton-Culver, H. Tags: Tumor Microenvironment and Metastasis Source Type: research
Abstract B21: Exostosin 1 regulates cancer cell stemness in breast cancer cells
Cancer stem cells (CSCs), a group of cancer cells, are associated with resistance to radiation and chemotherapy and are implicated in recurrent of cancer. Exostosin 1 (EXT1) gene is widely reported as tumor suppressor and its indispensable role in elongation of heparan sulfate (HS) can speculate probable role as tumor promotor. In recent years, a number of tumors are reported to over express EXT1. Here, we investigated the role of EXT1 in the maintenance of cancer cell stemness. MCF7/ADR cells developed by exposing MCF7, breast cancer cells, to doxorubicin for several months in culture, showed high resistance to doxorubici...
Source: Cancer Research - July 27, 2016 Category: Cancer & Oncology Authors: Manandhar, S., Kim, C.-g., Oh, S. Y., Lee, S.-H., Seok, J., Jung, Y.-D., Lee, H.-E., Choi, Y.-S., Lee, Y. M. Tags: Therapeutic Targeting Tumor Microenvironment Source Type: research
Abstract PR07: Dissection of cancer cells extravasation through human vascularized 3D microfluidic model: The major role of talin-1
Cancer cells spread from a primary tumor to secondary loci is responsible for more than 90% of cancer related mortality. Hematogenous metastasis is a complex process [1]. It includes a chain of events that can be summarized as follows: migration from primary tumor site and intravasation of the primary tumor cancer cells into the blood flow, dissemination through the circulation, extravasation in different organs, survival in the new microenvironment and colonization with generation of a new tumor.Recently our group presented a microfluidic 3D model reproducing the effects of the CXCL5-CXCR2 interaction between bone cells a...
Source: Cancer Research - May 25, 2016 Category: Cancer & Oncology Authors: Gilardi, M., Bersini, S., Kamm, R. D., Moretti, M., Vanoni, M. Tags: Circulating Evidence of Tumor Metastasis Source Type: research
