bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1350: Genetic variations in apoptosis pathway are associated with survival in late stage non-small cell lung cancer.
Authors: Shu Xiang , Lu Charles , Chang Joe Y. , Roth Jack A. , Wu Xifeng 
Published: August 2014

Abstract
Dysregulation of apoptosis pathway plays an essential role in carcinogenesis, tumor progression, and resistance to chemotherapy. We hypothesized that genetic variations in genes involved in the apoptosis pathway may affect the survival in late stage non-small cell lung cancer (NSCLC) patients. To test this hypothesis, we genotyped 583 tagging SNPs in 598 late stage NSCLC patients and analyzed their associations with survival individually and jointly. Seven SNPs were statistically significantly associated with overall survival after correction for multiple comparisons (q&lt;0.1). The most significant SNP was rs17592236 on FOXO1 gene under the dominant model (OR: 2.54, 95%CI: 1.71-3.78, p=4.15x10−6). We also observed a significant cumulative effect. Compared to the reference group (patients with no more than two risk alleles), those having five or more risk alleles were much more likely to die within seven months (HR: 3.58, 95% CI: 2.55-5.04, p&lt;0.001). Notably, the median survival time (MST) was significantly reduced by up to 15 months in high risk patients when compared to the reference group (MST: 22.2 months, p&lt;0.001). Survival tree analysis revealed potential higher order gene-gene interactions among these SNPs. Our results provided evidence that genetic variations in the apoptosis pathway modulate NSCLC survival and may serve as biomarkers to differentiate NSCLC patients with different prognosis.
Citation Format: Xiang Shu, Charles Lu, Joe Y. Chang, Jack A. Roth, Xifeng Wu. Genetic variations in apoptosis pathway are associated with survival in late stage non-small cell lung cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1350. doi:10.1158/1538-7445.AM2013-1350
Abstract 1354: Chronic social stress in a mouse model of triple-negative breast cancer is associated with oncogenic changes in mammary fat.
Authors: Volden Paul A. , Wonder Erin , Skor Maxwell , Patel Feenalie , McClintock Martha , Brady Matthew , Conzen Suzanne 
Published: August 2014

Abstract
Chronic social isolation is linked to increased mammary tumor growth in rodent models of breast cancer. In the C3(1)/SV40 T-antigen (Tag) FVB/N mouse model of “triple-negative” breast cancer, the heightened stress response elicited by social isolation has been associated with increased expression of metabolic genes in the mammary gland before invasive tumors develop (i.e. during the in situ carcinoma stage). To further understand how underlying accelerated mammary tumor growth is associated with social isolation, we separated the mammary gland adipose tissue from adjacent ductal epithelial cells and analyzed individual cell types for changes in metabolic gene expression. Specifically, increased expression of the key metabolic genes Acaca, Hk2 and Acly was found primarily in the adipocyte, rather than epithelial fraction. Increased metabolic gene expression in the mammary adipocytes of socially isolated mice coincided with increased glucose metabolism, lipid synthesis, and leptin expression. Furthermore, culture media from isolated mouse mammary adipose tissue resulted in relatively increased proliferation and decreased apoptosis of mammary epithelial cancer cells derived from the same mouse strain. Additional gene expression analyses identified significant upregulation of the novel carbohydrate response element binding protein beta isoform (CHREBP-β) in socially isolated mammary fat. We hypothesize that the response to social isolation induces metabolic changes in mammary fat that are coordinated through CHREBP-β and are pro-oncogenic. We are currently performing global lipidomic and metabolomic analyses of mammary adipose tissue and secreted culture media to identify bioactive molecules involved in tumor growth.
Citation Format: Paul A. Volden, Erin Wonder, Maxwell Skor, Feenalie Patel, Martha McClintock, Matthew Brady, Suzanne Conzen. Chronic social stress in a mouse model of triple-negative breast cancer is associated with oncogenic changes in mammary fat. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1354. doi:10.1158/1538-7445.AM2013-1354
Abstract 1409: Genetic ablation of lymphoma development inp53 knockout mice reveals a novel model of osteosarcoma and hemangiosarcoma.
Authors: Landuzzi Lorena , Nicoletti Giordano , Palladini Arianna , Ianzano Marianna , Grosso Valentina , Ranieri Dario , De Giovanni Carla , Lollini Pier-Luigi , Nanni Patrizia 
Published: August 2014

Abstract
Homozygous knockout of p53 in mice leads to early mortality from lymphoma, with almost complete penetrance, thus hampering the study of other tumor histotypes related to p53. To ablate lymphoma development, we crossed p53 knockout mice with Rag2-/-;Il2rg-/- (RGKO) mice, which lack T, B and NK cells. We then compared the tumor spectrum of homozygous (p53-/-) and heterozygous (p53+/-) mice with those of mice lacking lymphocytes (RGKO-p53-/- and RGKO-p53+/-, respectively). All mice were of BALB/c genetic background. Lymphoma incidence in p53-/- mice exceeded 80%, whereas in RGKO-p53-/- it was near zero. The prevalent tumor of RGKO-p53-/- mice was hemangiosarcoma (incidence was about 60%in both sexes, median latency 19 weeks), other tumors included soft tissue sarcomas (incidence ∼10%), osteosarcomas and mammary carcinomas. Changes in tumor spectrum occurred also in p53 heterozygotes, in which lymphomas were relatively rare (&lt;20%). Male RGKO-p53+/- had an increased incidence of hemangiosarcomas, reaching ∼25%, whereas females had an increased incidence of osteosarcomas, reaching ∼20%. The latter shared with human osteosarcoma the involvement of limbs and a high metastatic ability, in particular to the lungs. Molecular studies of tumors, in vitro cultured tumor cells and established cell lines showed specific alterations in the expression of p53-related genes (p16Ink4a, p19Arf, p15Ink4b, p21Cip1) and high expression levels of insulin-like growth factors and their receptors. In conclusion, genetic ablation of lymphoma in p53 knockout mice led to the development of new models of sarcoma development that can be now explored to study the development and metastatic spread of hemangiosarcoma and osteosarcoma.
Citation Format: Lorena Landuzzi, Giordano Nicoletti, Arianna Palladini, Marianna Ianzano, Valentina Grosso, Dario Ranieri, Carla De Giovanni, Pier-Luigi Lollini, Patrizia Nanni. Genetic ablation of lymphoma development inp53 knockout mice reveals a novel model of osteosarcoma and hemangiosarcoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1409. doi:10.1158/1538-7445.AM2013-1409
Abstract 1411: Pathogenesis and treatment of rhabdomyosarcoma in a susceptible murine model.
Authors: Zaid-Kaylani Samer , Pressey Joseph G. , Kelly David R. , Athar Mohammad 
Published: August 2014

Abstract
Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma of childhood. While the establishment of standard multi-modal therapy has led to improved survival, new therapeutic approaches are desperately needed to improve outcomes in patients with metastatic and recurrent disease. Our objective was to develop a highly penetrant mouse model of RMS to study the molecular pathways of the disease and to evaluate novel anticancer agents for the treatment of RMS. The hedgehog (Hh) pathway has been demonstrated to be activated in embryonal RMS. Communication between Hh and PI3K/AKT/mTOR pathways provides a rationale for the study of mTOR inhibitors such as rapamycin in RMS therapy. We developed a novel RMS mouse model by breeding Ptch6-7 knockouts onto a tumor susceptible SKH1 genetic background. We employed these animals (n=20/group) to study the effects of mTOR inhibitor, rapamycin, on the growth and progression of RMS tumors. We found that 42% of the Ptch1+/−SKH1 mice receiving no treatment developed RMS. These tumors were confirmed to have embryonal RMS morphology. These animals spontaneously develop RMS with embryonal histology predominantly in the hind limbs. The tumors developed at approximately 20 weeks of age; thereafter they grew very prolifically. Molecular studies demonstrated high expression of both Myogenin and Myf5. The tumors also manifested Hh pathway activation. The RMS bearing animals were divided into two groups with a third group of Ptch+/+ mice acting as a wild-type control group. Group-I animals receiving no treatment served as positive controls. The increase in tumor size in these animals was compared with the tumor growth of animals treated with rapamycin. The treatment resulted in a significant decrease in the rate of tumor growth as compared to the control group (p&lt;0.05). This treatment also reduced the expression of AKT and Hh pathways, which was consistent with the tumor inhibitory response seen on a gross level. Decreases in markers of tumor invasiveness and VEGF expression were also noted. We conclude that the Ptch1+/− Skh1 mouse represents a novel murine model for aggressive embryonal RMS that recapitulates the pathobiology of human disease. Rapamycin effectively inhibits the growth of Ptch1+/− Skh1 RMS tumors providing insight into the mechanism underlying RMS tumorigenesis. mTOR inhibition with possible Hh pathway cross talk inhibition represents a promising target in the treatment of RMS in this murine model.
Citation Format: Samer Zaid-Kaylani, Joseph G. Pressey, David R. Kelly, Mohammad Athar. Pathogenesis and treatment of rhabdomyosarcoma in a susceptible murine model. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1411. doi:10.1158/1538-7445.AM2013-1411
Abstract 1414: The role of RUNX3 and RUNX3-related chemokines in lung cancer-induced bone resorption.
Authors: Kim Hyun-Jeong , Chung Won-Yoon , Park Kwang-Kyun 
Published: August 2014

Abstract
Lung cancer frequently metastasizes to bone, which is associated with significant morbidity and a dismal prognosis. Runt-related transcription factor 3 (RUNX3) functions as a tumor suppressor in many cancers, and may be also important in the development of lung cancer. In this study, we found that RUNX3 knockdown increased the proliferation, migration and invasion of human lung cancer A549 cells. Interestingly, the receptor activator of nuclear factor-kappaB ligand (RANKL)/osteoprotegerin (OPG) ratio, an index of osteoclastogenic stimulation, was significantly increased in human osteoblastic hFOB1.19 cells treated with RUNX3 knockdown A549 cell-derived conditioned medium (CM) as compared to CM of RUNX3-expressing A549 cells. In the chemokine and receptor PCR array to identify RUNX3-regulated factors that mediate bone invasion of lung cancer cells, RUNX3 knockdown led to upregulation of CCL5 and downregulation of CCL19 and CXCL11 in A549 cells. CCL5 increased the proliferation, migration and invasion of A549 cells but CCL19 and CXCL11 had not a remarkable effect. CCL5 increased RANKL/OPG ratio in hFOB1.19 cells but CCL19 and CXCL11 decreased. CCL5 promoted RANKL-induced osteoclast differentiation in BMMs, while CCL19 and CXCL11 reduced. In the mouse model that RUNX3-expressing or RUNX3 knockdown A549 cells were injected subcutaneously over the calvaria, RUNX3 knockdown resulted in the increased tumor size and severe bone destruction. Additionally, in the osteolytic bone invasion model that the cells were inoculated into bone marrow of mouse tibia, bone lesions appeared more seriously in mice injected with RUNX3 knockdown A549 cells. The serum level of CCL5 was increased, while those of CCL19 and CXCL11 were decreased, in RUNX3 knockdown A549 cell-inoculated mice as compared with RUNX3-expressing A549 cell-inoculated mice. Taken together, bone invasion of lung cancer cells may be closely related with RUNX3 and RUNX3-regulated chemokines.
Citation Format: Hyun-Jeong Kim, Won-Yoon Chung, Kwang-Kyun Park. The role of RUNX3 and RUNX3-related chemokines in lung cancer-induced bone resorption. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1414. doi:10.1158/1538-7445.AM2013-1414
Abstract 1417: CXCR2 plays critical roles in colitis and colitis-associated cancer through trafficking of myeloid-derived suppressor cells.
Authors: Katoh Hiroshi , Wang Dingzhi , Kim Sun-Hee , DuBois Raymond N. 
Published: August 2014

Abstract
A large body of evidence indicates that chronic inflammation is a risk factor for colorectal cancer (CRC). However, all of the mechanisms by which inflammation promotes CRC development are not fully understood. Our lab previously showed that PGE2 promotes CRC progression through angiogenic chemokine CXCL1 (Wang et al., 2006). CXCL1 exerts its downstream functions via binding to its receptor, CXCR2, which is a G-protein-coupled receptor. Our previous study showed that CXCR2 expression is also elevated mainly in endothelial and immune cells of human colorectal carcinomas. CXCR2 is expressed on neutrophils and involved in neutrophil trafficking. These results prompted us to hypothesize that CXCR2 may be one of mediators connecting inflammation and CRC. To address this question, preliminary experiments were performed to determine whether CXCR2 is involved in inflammation-enhanced CRC progression.
Our results revealed that deletion of CXCR2 significantly attenuated AOM/DSS induction of chronic colonic inflammation and tumor burden, suggesting that CXCR2 is required for promoting chronic inflammation and tumor formation and growth in the colon. Among immunocytes we tested, loss of CXCR2 only significantly suppressed a massive infiltration of MDSCs (CD11b+Ly6G+) into the colonic mucosa in both normal (water treatment) and chronic inflammatory (DSS treatment) conditions. We further found that the status of CXCR2 did not affect MDSC populations in the bone marrow of mice treated with either water or DSS. Interestingly, treatment with DSS more dramatically reduced MDSC populations in the circulatory system of WT mice than of CXCR2 knockout mice, suggesting that CXCR2-deficient MDSCs have less ability to migrate to local organs. Our in vitro results further demonstrated that treatment with CXCL1 or CXCL5 were able to induce chemotaxis of WT-mice derived MDSCs but not MDSCs isolated from CXCR2-/- mice. Collectively, these results suggest that CXCR2-expressing MDSCs contribute to chronic inflammation and colitis-associated tumor formation and growth. Our findings are novel and provide a rationale for development of new therapeutic approaches to subvert tumor-induced immunosuppression by using CXCR2 antagonists and neutralized antibodies.
Citation Format: Hiroshi Katoh, Dingzhi Wang, Sun-Hee Kim, Raymond N. DuBois. CXCR2 plays critical roles in colitis and colitis-associated cancer through trafficking of myeloid-derived suppressor cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1417. doi:10.1158/1538-7445.AM2013-1417
Abstract 1430: The role of IL27 as a driver of skin carcinogenesis.
Authors: Dibra Denada , Newman Melissa , Cutrera Jeffry , Li Shulin 
Published: August 2014

Abstract
Although the genetic components that drive carcinogenesis and the stem cell involvement in cancer initiation have been established, the mechanism through which the immune response/cytokine milieu within the tumor microenvironment promotes cancer formation and stem cell behavior is an exciting yet understudied area of research. This statement is specifically true with an important regulator of the immune response, IL27, which is known to have both pro- and anti-inflammatory properties. During an inflammatory response, IL27 has been shown to regulate two canonical cytokines IL10 and IL17, and to affect multiple inflammatory and infectious diseases. Yet, the function of IL27 at physiological levels during the instigation of carcinogenesis remains unknown. To determine the role of IL27 during the early stages of cancer formation, the well-established two step skin carcinogenesis model (DMBA followed by the promoter benzoyl peroxide (BP)) was used. Interestingly, mice that lack IL27 signaling (IL27RA-/-) are protected during the initiation of carcinogenesis as they have lower incidence of papilloma formation over time when compared to wildtype mice. Additionally, wildtype mice treated with IL27 via gene therapy have a higher incidence and develop more papillomas when compared to control counterparts. Bone marrow transfer studies showed that IL27 signaling in both hematopoietic and non-hematopoietic cells is needed to drive skin carcinogenesis. Additionally, IL27 signaling induces loss of epithelial stem cell homeostasis/maintenance. In mice treated with DMBA/BP, 23% of the wildtype mice treated had ulcerations that failed to heal over time, while none of IL27RA-/- showed any defects in the skin. In mice that went under bone marrow transfer followed by DMBA/BP, 40% of wildtype ones developed severe skin ulcerations, while none of the IL27RA-/- developed any skin abnormalities. And lastly, mice undergoing the tumorigenesis protocol that were treated with IL27 developed hair loss, which was mirrored by loss of hair follicles. These phenotypes are like due to the loss of epithelial stem cell maintenance and/or homeostasis by IL27. These finding propose an unrecognized role of IL27 in promoting papilloma formation and disrupting epithelial cell maintenance and/or homeostasis.
Citation Format: Denada Dibra, Melissa Newman, Jeffry Cutrera, Shulin Li. The role of IL27 as a driver of skin carcinogenesis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1430. doi:10.1158/1538-7445.AM2013-1430
Abstract 1460: Quantification of circulating tumor cells using multiplexed Surface-Enhanced Raman Scattering Nanoparticles.
Authors: Wang Xu , Qian Ximei , Beitler Jonathan J. , Chen Zhuo (Georgia) , Khuri Fadlo R. , Lewis Melinda M. , Shin Hyung J. , Nie Shuming , Shin Dong M. 
Published: August 2014

Abstract
Background: Detection, quantification, and molecular characterization of CTCs may aid physicians in treatment decision making and optimizing. However, the major challenge in the detection and characterization of CTCs is the lack of a highly specific and sensitive assay to isolate and identify the rare population of CTCs in complex blood samples. Moreover, current approaches for CTC detection including CellSearch (FDA approved CTC detection method) which primarily relays on single biomarker are suboptimal because of tumor heterogeneity. Here we develop a multiplexed single-tube assay for directly detection of CTCs in blood sample using two targeted Surface-Enhanced Raman scattering (SERS) nanoparticles. Methods: SERS nanoparticles (60 nm) were prepared by spectral encoding with a Raman reporter molecule (QSY or BHQ) and then stabilized and protected by low molecular weight polyethylene glycols (PEGs). A targeting ligand, epidermal growth factor (EGF) peptide or epithelial cell adhesion molecule (EpCAM) antibody, was covalently conjugated to PEG layer of SERS nanoparticle. The functionalized EGF- or EpCAM- SERS nanoparticle was able to identify CTCs in the peripheral blood with high specificity and affinity. Results: We collected and examined fresh blood samples from 20 SCCHN patients with various histologies and successfully detected positive SERS signals that were greater than background in 9 of 12 (75%) of patients. This technique was demonstrated to be capable of identifying rare CTCs by two biomarkers simultaneously, with a range of 5-720 cells per ml of whole blood. Blood samples from 3 normal controls did not show any CTCs. In one patient who had 0 count of CTC detected by EGFR-targeting SERS tag showed 170 CTCs/ml of blood detected by EpCAM-targeting SERS tags. Conclusion: Special design of the two SERS nanoparticles, distinguished with unique spectral signatures and bio-conjugation of EGF or EpCAM antibody as targeting molecule, allowed simultaneous detection of epidermal growth factor receptor (EGFR) or EpCAM on CTCs in one blood sample. Our technique based on two biomarkers rather than those relayed on single biomarker may improve CTC assessment in clinical settings. (This research was supported by the National Cancer Institute award 5 P50 CA128613 and U54CA119338-04).
Citation Format: Xu Wang, Ximei Qian, Jonathan J. Beitler, Zhuo (Georgia) Chen, Fadlo R. Khuri, Melinda M. Lewis, Hyung J. Shin, Shuming Nie, Dong M. Shin. Quantification of circulating tumor cells using multiplexed Surface-Enhanced Raman Scattering Nanoparticles. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1460. doi:10.1158/1538-7445.AM2013-1460