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Source: Cancer Research
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Total 807 results found since Jan 2013.
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
Abstract B22: Loss of LncRNA XIST induces Epithelial to Mesenchymal Transition in Breast Cancer
Brain is one of the major sites of metastasis of breast cancer, and approximately 20% of patients with aggressive breast cancer eventually develop the metastatic disease in the brain. Long non-coding RNAs (lncRNA) have recently drawn much attention due to their wide functional variations and potential roles in tumor progression. By performing lncRNA array analysis comparing non-metastatic primary tumors with brain metastatic tumors from breast cancer patients, we identified that lncRNA XIST expression was significantly down-regulated in brain metastatic tumors. The result of Taqman PCR validated the results in tumor sample...
Source: Cancer Research - May 25, 2016 Category: Cancer & Oncology Authors: Liu, Y., Xing, F., Wu, K., Sharma, S., Watabe, K. Tags: Genetics and Evolution of Metastatic Tumors Source Type: research
Abstract B36: Rab25 aggravates cancer cell invasion through Snail expression
Conclusion: Our results show for the first time that Snail mediates Rab25-induced cancer cell EMT and invasiveness through a beta1 integrin /Akt/GSK-3beta signaling cascade, providing novel biomarkers, and potential therapeutic targets for deadly cancers.Citation Format: Bo Young Jeong, Kyung Hwa Cho, Seung Hwa Kim, Yu Na Kim, Chang Gyo Park, Hoi Young Lee. Rab25 aggravates cancer cell invasion through Snail expression. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Metastasis; 2015 Nov 30-Dec 3; Austin, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(7 Suppl):Abstract nr B36.
Source: Cancer Research - May 25, 2016 Category: Cancer & Oncology Authors: Jeong, B. Y., Cho, K. H., Kim, S. H., Kim, Y. N., Park, C. G., Lee, H. Y. Tags: Metastatic Cell Plasticity Source Type: research
Abstract PR10: The chromatin remodeler CHD4 as a potential specific target for alveolar rhabdomyosarcoma therapy
Fusion-positive alveolar rhabdomyosarcoma (FP-RMS) is a paediatric tumour driven by an oncogenic fusion transcription factor, PAX3-FOXO1. Conventional chemotherapy is only effective for low risk patients which carry no metastasis, achieving a 5-year overall survival of 65%. The unique presence of this fusion protein in FP-RMS as well as the tumour cell survival dependency on PAX3-FOXO1 make this transcription factor a promising target for therapy. However, due to the difficulties associated with drug development targeting transcription factors, we performed a combined proteomic and genetic screen to identify new druggable ...
Source: Cancer Research - April 3, 2016 Category: Cancer & Oncology Authors: Marques, J., Boehm, M., Wachtel, M., Schaefer, B. Tags: Epigenetics Source Type: research
Abstract A18: Epigenetic profiling uncovers the suppressive role of caveolae in Ewing sarcoma
Ewing sarcoma (ES) is the second most common bone tumor in childhood. ES harbors a characteristic gene translocation that gives rise to a fusion protein, most commonly EWS/FLI1 (EF). Caveolin-1 (CAV1) is a direct target of EF, it is overexpressed in ES and has an oncogenic role. CAV1 and the Polymerase I and transcript release factor (PTRF) interact at the plasma membrane and are essential for caveolae formation. The methylome analysis of ES samples and cell lines revealed a hypermethylation in the N-shore islands of the PTRF promoter compared to normal cells. We hypothesize that, as ES cells have very few caveolae and do ...
Source: Cancer Research - April 3, 2016 Category: Cancer & Oncology Authors: Huertas–Martinez, J., Court, F., Rello–Varona, S., Martin, D. H., Almacellas, O., Sainz–Jaspeado, M., Garcia–Monclus, S., Lagares–Tena, L., Buȷ, R., Hontecillas–Prieto, L., Mateo–Lozano, S., Sastre, A., Azo Tags: Epigenetics Source Type: research
Abstract B31: Combined siRNA and small molecule screening identifies Aurora B kinase as an effective target in MYCN-driven neuroblastoma
Despite advances in multimodal treatment, neuroblastoma (NB) is often fatal for children with high-risk disease and many survivors need to cope with long-term side effects from high-dose chemotherapy and radiation. To identify new therapeutic targets, we performed a siRNA screen of the druggable genome combined with a small molecule screen of 465 compounds targeting 39 different mechanisms of actions in four NB cell lines. We identified 58 genes as targets, including AURKB, in at least one cell line. In the drug screen, aurora kinase inhibitors (nine molecules) and in particular the AURKB-selective compound, barasertib, we...
Source: Cancer Research - April 3, 2016 Category: Cancer & Oncology Authors: Bogen, D., Wei, J. S., Azorsa, D. O., Ormanoglu, P., Buehler, E., Guha, R., Keller, J. M., Griner, L. A. M., Ferrer, M., Song, Y. K., Liao, H., Mendoza, A., Gryder, B. E., Sindri, S., He, J., Wen, X., , Zhang, S., Shern, J. F., Yohe, M. E., Taschner-Mandl Tags: Targeted Therapeutics and Resistance Source Type: research
DDR1 Inhibition Enhances Immunotoxin Therapy
Recombinant immunotoxins (RIT) have been highly successful in cancer therapy due, in part, to the high cancer-specific expression of cell surface antigens such as mesothelin, which is overexpressed in mesothelioma, ovarian, lung, breast, and pancreatic cancers, but is limited in normal cells. RG7787 is a clinically optimized RIT consisting of a humanized anti-mesothelin Fab fused to domain III of Pseudomonas exotoxin A, in which immunogenic B-cell epitopes are silenced. To enhance the therapeutic efficacy of RITs, we conducted a kinome RNAi sensitization screen, which identified discoidin domain receptor 1 (DDR1), a collag...
Source: Cancer Research - March 14, 2016 Category: Cancer & Oncology Authors: Ali-Rahmani, F., FitzGerald, D. J., Martin, S., Patel, P., Prunotto, M., Ormanoglu, P., Thomas, C., Pastan, I. Tags: Therapeutics, Targets, and Chemical Biology Source Type: research
GALNT1-Mediated SHH Activation in BCSCs
In this study, we generated a mAb (BCMab1) against CD44+ human bladder cancer cells that recognizes aberrantly glycosylated integrin α3β1. The combination of BCMab1 with an anti-CD44 antibody identified a BCMab1+CD44+ cell subpopulation as BCSCs with stem cell–like properties. Gene expression analysis revealed that the hedgehog pathway was activated in the BCMab1+CD44+ subpopulation and was required for BCSC self-renewal. Furthermore, the glycotransferase GALNT1 was highly expressed in BCMab1+CD44+ cells and correlated with clinicopathologic features of bladder cancers. Mechanistically, GALNT1 mediated O-linked glycosy...
Source: Cancer Research - February 29, 2016 Category: Cancer & Oncology Authors: Li, C., Du, Y., Yang, Z., He, L., Wang, Y., Hao, L., Ding, M., Yan, R., Wang, J., Fan, Z. Tags: Tumor and Stem Cell Biology Source Type: research
Abstract P2-05-26: Focal adhesion kinase is required for efficient tumor-induced osteoclastogenesis via control of macrophage colony stimulating factor expression
Breast cancer most commonly metastasizes to bone where metastases cause the potentiation of the vicious cycle. During this process, breast cancer bone metastases inhibit osteoblasts from forming new bone, while also activating osteoclasts to degrade bone. This in turn causes release of bone-matrix bound growth factors which propagate tumor growth. The overall net bone destruction can lead to significant adverse clinical consequences for patients including fractures or substantial pain. While agents such as bisphosphonates or the monoclonal antibody to RANKL denosumab, both of which inhibit the osteolytic activity of osteoc...
Source: Cancer Research - February 18, 2016 Category: Cancer & Oncology Authors: Landon, K., Howe, G., Zhao, H., Addison, C. Tags: Poster Session Abstracts Source Type: research
Abstract P1-05-04: A novel mechanism of epithelial-mesenchymal transition in breast cancer metastasis: Involvement of prostanoid receptor
Conclusion: Our results showed that EP2 promoted EMT and breast cancer metastasis through the downregulation of SLC19A3 expression. Taken together, targeting EP2/SLC19A3 signaling pathway maybe a potential treatment for metastasis and adjuvant chemotherapy to reduce the metastatic risk.Citation Format: Kwong A, Siu MT, Cheuk I, Ho JC, Chen J, Shin VY. A novel mechanism of epithelial-mesenchymal transition in breast cancer metastasis: Involvement of prostanoid receptor. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AA...
Source: Cancer Research - February 18, 2016 Category: Cancer & Oncology Authors: Kwong, A., Siu, M., Cheuk, I., Ho, J., Chen, J., Shin, V. Tags: Poster Session Abstracts Source Type: research
Abstract P1-05-06: Essential role of notch-4/STAT3 signaling in epithelial-mesenchymal transition of tamoxifen-resistant human breast cancer
In conclusion, inhibition of Notch signaling may have efficacy in the treatment of breast cancer metastasis.Citation Format: Bui QT, Kang KW. Essential role of notch-4/STAT3 signaling in epithelial-mesenchymal transition of tamoxifen-resistant human breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-05-06.
Source: Cancer Research - February 18, 2016 Category: Cancer & Oncology Authors: Bui, Q., Kang, K. Tags: Poster Session Abstracts Source Type: research
Abstract PD2-06: Inhibition of 3-phosphoinositide dependent protein kinase 1 (PDK1) synergizes with CDK4/6 inhibitors against ER-positive breast cancer
Conclusions: These data support a critical role of PDK1 in mediating acquired resistance to CDK4/6 inhibitors in ER+ breast cancer cells. Co-targeting of the PDK1 and CDK4/6 pathways may overcome resistance to CDK4/6 inhibitors and is worthy of further translational and clinical investigation in patients with ER+ breast cancer.Citation Format: Jansen VM, Bhola NE, Bauer JA, Formisano L, Moore P, Koch J, Arteaga CL. Inhibition of 3-phosphoinositide dependent protein kinase 1 (PDK1) synergizes with CDK4/6 inhibitors against ER-positive breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Anton...
Source: Cancer Research - February 18, 2016 Category: Cancer & Oncology Authors: Jansen, V., Bhola, N., Bauer, J., Formisano, L., Moore, P., Koch, J., Arteaga, C. Tags: Poster Discussion Abstracts Source Type: research
Abstract S3-03: Nuclear FGFR1 interaction with estrogen receptor (ER) {alpha} is associated with resistance to endocrine therapy in ER+/FGFR1-amplified breast cancer
Conclusions: These data support a critical role of ER and FGFR1 interaction in endocrine resistance in ER+/FGFR1-amplified breast cancer. Targeting of FGFR1 in combination with antiestrogens may abrogate resistance to endocrine therapy in these tumors and is worthy of clinical investigation.Citation Format: Formisano L, Young CD, Bhola NE, Bulen B, Estrada VM, Wagle N, Van Allen E, Red Brewer ML, Jansen VM, Guerrero AL, Giltnane JM, Strcker T, Arteaga CL. Nuclear FGFR1 interaction with estrogen receptor (ER) α is associated with resistance to endocrine therapy in ER+/FGFR1-amplified breast cancer. [abstract]. In: Proceedi...
Source: Cancer Research - February 18, 2016 Category: Cancer & Oncology Authors: Formisano, L., Young, C., Bhola, N., Bulen, B., Estrada, V., Wagle, N., Van Allen, E., Red Brewer, M., Jansen, V., Guerrero, A., Giltnane, J., Strcker, T., Arteaga, C. Tags: General Session Abstracts Source Type: research
Abstract P3-04-02: Invasive lobular carcinoma cell lines utilize WNT4 signaling to mediate estrogen-induced growth
Invasive lobular carcinoma (ILC) is a histological subtype of breast cancer representing 10-15% of newly diagnosed breast tumors. Over 90% of ILC are estrogen receptor (ER)-positive, however, endocrine response and estrogen signaling are not well understood in ILC. Retrospective analyses suggest that ILC patients treated with endocrine therapy have poorer outcomes than invasive ductal carcinoma (IDC) patients, and that ILC patients may not benefit from adjuvant tamoxifen. Based on these observations, we hypothesize that ER regulates unique signaling pathways in ILC cells that control growth and endocrine response.To identi...
Source: Cancer Research - February 18, 2016 Category: Cancer & Oncology Authors: Sikora, M., Oesterreich, S. Tags: Poster Session Abstracts Source Type: research
Abstract S4-05: Interrogating the landscape of long noncoding RNAs in breast cancer to identify predictors of tamoxifen resistance
Conclusion: In this study, we develop the largest reported compendia of breast cancer lncRNAs. We prioritize BRCAT431 as the top lncRNA upregulated in ER-positive breast cancers, and demonstrate that it confers aggressive oncogenic phenotypes in vitro and in vivo. We identify a novel mechanism by which this lncRNA functions. Our results suggest that by promoting tamoxifen resistance, BRCAT431 increases the clinical risk of recurrence and metastases in breast cancer. Overall, this study supports the rationale for investigating lncRNAs as novel biomarkers and therapeutic targets in breast cancer.Citation Format: Feng FY, Nik...
Source: Cancer Research - February 18, 2016 Category: Cancer & Oncology Authors: Feng, F., Niknafs, Y., Han, S., Ma, T., Speers, C., Malik, R., Evans, J., Zhang, C., Pierce, L., Hayes, D., Rae, J., Chinnaiyan, A. Tags: General Session Abstracts Source Type: research
