bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1327: Study the effect of IGFBP5 in human fibroblast cells
Authors: Lin Hsin-Ying , Shen Cheng-Ying , Lai Liang-Chuan , Chuang Eric Y. , Tsai Mong-Hsun 
Published: February 2011

Abstract
Retinoblastoma (Rb) is a rapidly developing cancer which develops in the cells of the retina, the light detecting tissue of the eye. It is the most common primary ocular malignancy (eye cancer) of childhood. There are both hereditary and sporadic forms of retinoblastoma. The hereditary form of retinoblastoma is associated with a germ line mutation in one of the RB genes and is characterized by the occurrence of multiple, bilateral Rb tumors and a predisposition to the development of second cancers. These second tumors often occur in patients treated by radiation therapy. In the previous study, an unexpected hypersensitivity to ionizing radiation in skin fibroblasts derived from unaffected parents of children with hereditary Rb was observed. By use of the prediction analysis for microarrays (PAM) and principal component analysis (PCA), 42 significantly differential expressed genes were selected and identified as radiosensitive genes. Therefore, one of these 42 genes, IGFBP5 (insulin-like growth factor binding protein 5) was chosen to further investigate the role in radiosensitivity in fibroblast cells. IGFBP5 was overexpressed or knocked down in HS68 (the human foreskin fibroblast) cells. The cells were irradiated with γ -ray, and then counted and seeded into the plates for colony formation assays. According to the results, IGFBP5-ovexpressed cells seemed to be more resistant to radiation. Also, IGFBP5 knocked down cells might be more sensitive to radiation under low dose of radiation. In summary, these results suggested that IGFBP5 may play a role in radiosensitivity in human fibroblast cells.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1327.
Abstract 1328: p53 represses microRNAs let-7a and let-7b in response to ionizing radiation
Authors: Saleh Anthony D. , Savage Jason E. , Ly David , Nguyen Phuongmai , Cao Lui , Soule Benjamin P. , Dan Tu D. , DeGraff William , Finkel Toren , Harris Curtis C. , Mitchel James B. , Gius David , Simone Nicole L. 
Published: February 2011

Abstract
Radiation-induced free radicals damage cells resulting in a stress response that involves large scale changes in gene expression including microRNAs (miRNA). Specifically, decreased expression of the let-7 family of miRNA has been reported. let-7 regulates cell cycle and DNA repair proteins such as Ras, cyclin D1, Rad 18 and Rad 51, which can all effect the radiation response. However, the precise role of the let-7 family and the mechanisms regulating this repression has not been elucidated. In this study, we demonstrate a mechanism underlying the let-7a3 and let-7b response to radiation exposure. Using real time RT-PCR we demonstrate that let-7a and b expression decreases by 80-90% in response to 0.5-10 Gy doses of IR in cultured HCT116 colon cancer cells. This effect is also observed by RT-PCR in response to other sources of geneotoxic stress such as etoposide or UV irradiation suggesting that a reduction in let-7 is common among DNA damaging events. We also show that this decrease in expression of let-7a and b is dependent on p53 as the decrease is absent in HCT116 p53 knockout cells. Further analysis of the effect of p53 on let-7a3 and b expression by CHIP showed an association of p53 with a predicted binding site in the host gene promoter. After treatment of mice with radiation a decrease in let-7a and b expression is observed in radio sensitive tissues. However no decrease was observed in tissues collected from p53 KO mice. Transfection of additional let-7a or let-7b into HCT116 cells decreased survival after radiation treatment, but survival is unchanged by increased let-7 in HCT116 p53 knockout cells. These results suggest that p53 can directly repress let-7 expression. Also, let-7 may play an important role in the regulation and fine-tuning of the p53 cell stress response to radiation. Furthermore, therapeutics aimed at inducing over expression of let-7 may be useful as radiation sensitizers.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1328.
Abstract 1329: Study the novel function of Semaphorin 6A in lung adenocarcinoma
Authors: Shen Cheng-Ying , Lu Tzu-Pin , Li Yung-Hua , Feng-Chang Wu , Lai Liang-Chuan , Chuang Eric Y. , Tsai Mong-Hsun 
Published: February 2011

Abstract
In Taiwan, most of female lung cancer patients are non-smoker (&gt;90%) and most of the tumor types are adenocarcinoma. The previous studies indicated that cooking oil fumes, late menopausal ages and HPV infections have been associated with the risk of lung adenocarcinoma among non-smoking female. In order to discover novel molecular targets of non-smoking female lung cancer patients in Taiwan, the paired normal and tumor tissues were collected from 60 female non-smoking lung cancer patients for microarray analysis. From the microarray results, we found that several genes in the semaphorin family, such as SEMA3B, SEMA3G, SEMA5A, SEMA6A, and SEMA6D, were significantly down-regulated in the tumor tissues. However, the specific mechanisms of the genes in lung cancer are still unclear. Among the semaphorin genes, SEMA6A was chosen for further study. The results of quantitative real-time PCR and immunohistochemistry showed significant down-regulation of SEMA6A in lung cancer tissues. Moreover, the A549 cell line was used to further investigate the function of SEMA6A. A549 cells with overexpressed SEMA6A were identified and purified the cell membrane fraction for western blotting. A wound healing assay was also performed to address the migration ability. The result was shown that the A549 cells with over expressed SEMA6A exhibited a lower capacity to fill the gap during 24 hours incubation compared with A549 cells. In summary, our data indicated that normal lung tissues express more SEMA6A protein which might inhibit the cell migration than the cancer lung tissues.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1329.
Abstract 1330: Low dose irradiation reverts chemoresistance towards fluorouracil in human pancreatic adenocarcinoma cells by upregulation of thymidine phosphorylase
Authors: Seeliger Hendrik , Xin Ying , Camaj Peter , Ischenko Ivan , Schaffer Moshe , Jauch Karl-Walter , Bruns Christiane J. 
Published: February 2011

Abstract
Background: Resistance towards cytotoxic drugs and ionizing radiation (IR) accounts for poor therapy response in pancreatic cancer. The radiosensitizing effects of fluorouracil (FU) are well characterized, however, it is not known whether IR itself exerts sensitizing effects towards cytotoxic chemotherapy. Here, we hypothesize that IR induced upregulation of thymidine phosphorylase (TP) results in a reversal of resistance towards FU.
Methods: An FU resistant variant of the human pancreatic adenocarcinoma cell line AsPC-1 was developed by long term in vitro FU exposure. Proliferation of AsPC-1 and AsPC-1FUres cells was determined by an MTT proliferation assay after previous low dose (0.05 Gy) exposure of IR. To antagonize a possible effect mediated by TP upregulation, anti-TP siRNA was added in the same setting. TP expression in AsPC-1 cells before and after IR was determined by Western blotting.
Results: FU resistant AsPC-1 cells showed a 7.5-fold increase of the IC50 after FU exposure, compared to non-resistant cells. When challenging both cell lines with FU after low dose IR, no significant difference of proliferation was observed in AsPC-1 cells and their FU resistant variant, suggesting a reversal of chemoresistance by IR. This chemosensitizing effect was abrogated when blocking TP by anti-TP siRNA before IR. In cell lysates harvested from AsPC-1 cells, an increase of TP expression was seen after exposure of low dose IR (0.05 Gy) as well as high dose IR (2.0 Gy).
Conclusion: Our results suggest a TP mediated reversal of chemoresistance towards FU that is triggered by low dose IR in vitro. These results have to be confirmed in an in vivo model. In conclusion, induction of TP expression by low dose irradiation may be an interesting concept to overcome chemotherapy resistance in pancreatic cancer.
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1330.
Abstract 1333: Upregulation of chemokines including RANTES/CCL5 upon Toll-like receptor 3 activation in breast cancer: Association with leukocyte infiltration
Authors: Venkatesh Amritha Kalyani , Pate Michelle , Benencia Fabian 
Published: February 2011

Abstract
The association of leukocytes with the microenvironment of different tumors and their role in disease progression is well-documented. However, the mechanism of recruitment of leukocytes to the tumor microenvironment remains unclear. In particular, we have previously demonstrated the capability of tumor-associated dendritic cells to promote neovascularization. In this light, toll-like receptors (TLR) have recently been identified as potential players in different cancers such as malignant melanomas, thyroid cancer and pancreatic cancer. These are a family of pattern-recognition receptors that, when activated by a ligand, trigger signaling pathways involved chiefly in the inflammation process of the innate immune system. Here, we investigated the role of TLR-3 in the capability of the tumor cells to generate chemokines capable of attracting leukocytes to the tumor microenvironment. For this purpose we used the 4T1 model of breast cancer in BALB/c mouse. First, we were able to determine the expression of TLR-3 in these cells by PCR analysis. Then, 4T1 mouse breast cancer cells were treated with poly(I:C), a well-known ligand for TLR-3, and the supernatants were checked for the presence of different chemokines (RANTES, SDF-1α, MIP-3α, MIP-3β) by sandwich ELISA. These molecules were selected taking into account that their receptors are present in dendritic cells. Further, a reverse transcription quantitative PCR was performed to detect the RNA expression levels of these chemokines. In both cases, a significant increase in RANTES levels upon TLR-3 activation was observed. Further, a chemokine PCR array showed upregulation of 10 chemokines, RANTES among them, on 4T1 cells stimulated with poly(I:C). A subsequent protein array analysis of different mouse cytokines in poly(I:C)-treated 4T1 cells revealed also an increase in RANTES, IL-6 and MIP-2 and a decrease in the matrix metalloprotease inhibitor TIMP-1. Interestingly, IL-6 upregulation was further confirmed by ELISA. These results are supportive of our hypothesis that TLR-3 activation could lead to the release of chemokines that assist in leukocyte recruitment. Further in vivo studies are required to observe the effect of knocking down TLR-3 in cancer cells on the capability of the tumor to promote leukocyte infiltration.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1333.
Abstract 1338: Chemokine (CXC motif) Ligand 5 protein expression in pancreatic tumors: Exploring chemostatic gradients in the tumor microenvironment
Authors: Ustach Carolyn V. , Whatcott Clifford J. , Kingsley Christopher , Hostetter Galen , Barret Michael , Hidalgo Manuel , Diep Caroline H. , Watanabe Aprill , Demeure Michael , Han Haiyong , Von Hoff Daniel D. 
Published: February 2011

Abstract
Due to lack of early presenting symptoms, pancreatic cancer is often diagnosed late when the tumor is highly invasive with aggressive clinical course and conventional therapies are limited in their effectiveness. Identifying molecular targets which contribute to tumor aggressiveness and metastasis could lead to development of better therapies to treat pancreas cancer patients. To identify potential molecular targets, we applied a specialized bioinformatics Breakpoint/Gene Aberration algorithm to analyze aCGH data and microarray expression data from 16 low-passage pancreas xenograft samples. Genes which were located near a putative breakpoint and whose expression was altered in a majority of the xenografts samples were considered putative targets. We report here preliminary data concerning one target, Chemokine (CXC motif) Ligand 5 (CXCL5) and its receptor CXCR2/IL8Rb. CXCL5 is a member of the ELR+ Chemokine family, a family of small, secreted ligands which are generally involved in cellular responses to injury and inflammation, but are also implicated in cancer progression and angiogenesis. CXCL5 is up regulated in 12 out of 16 xenograft samples analyzed (75%), with an average fold increase in expression of 41 (range 18 to 59). CXCL5 over-expression was further confirmed by IHC analysis of a custom made primary pancreas tumor microarray. Median IHC score (range 0-3) for CXCL5 in adenocarcinoma epithelial cells is 1.6, versus a median of 0.8 in the matched adjacent normal samples (N=34; p&lt;0.0007 using Mann-Whitney test). Interestingly, the receptor CXCR2 levels are increased in the stroma of tumor samples, with a median IHC score of 1.6 in the stroma surrounding ductal adenocarcinoma versus an IHC score of 0.6 in the stroma of adjacent normal ducts (N=31; p&lt;0.0001 using Mann-Whitney test). These results suggest the stroma surrounding the adenocarcinoma is responding to the over-expression of tumor-derived CXCL5. How CXCL5-induced CXCR2 signaling in the stroma impacts tumor growth and progression is currently being studied using an in-vitro co-culture system with established pancreas epithelial carcinoma cell lines and primary pancreas cancer fibroblasts. Results from these studies will be presented.
This work was supported by NIH P01 Grant CA109552.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1338.
Abstract 1339: Inhibition of chitinase-3-like-1 protein to suppress angiogenesis and enhance immune response in a mammary tumor model
Authors: Libreros Stephania , Garcia-Areas Ramon , Iragavarapu-Charyulu Vijaya L. 
Published: February 2011

Abstract
The purpose of this study is to determine whether inhibition of Chitinase-3-like 1 protein reduces the expression of angiogenic chemokines in macrophages while enhancing IFN-γ production in T cells. It is known that tumors can induce the upregulation of angiogenic and extracellular matrix degrading molecules. Tumor growth is often accompanied by immunosuppression. Our previous studies using the DA-3 mammary adenocarcinoma mouse model has shown that with tumor progression there is a profound down-regulation of interferon-gamma (IFN-γ), a crucial molecule involved in anti-tumor response. Additionally, angiogenic chemokines such as Monocyte Chemoattractant Protein-1 (CCL2/MCP-1) and Matrix Metalloproteinase-9 (MMP-9) are upregulated with mammary tumor growth. CCL2/MCP-1 is a known inflammatory chemoattractant for T cells and macrophages, and we have evidence that this molecule downregulates IFN-γ by the T lymphocytes. Recent studies have linked tumor progression with upregulation of Chitinase-3-like-1 protein (CHI3L1) in human breast cancer patients and that macrophages express this molecule during inflammatory processes. Our studies using DA-3 mammary breast cancer model indicate that CHI3L1 is expressed by DA-3 tumor cells. Expression of CHI3L1 in macrophages has been linked with upregulation of angiogenic chemokine, CCL2/MCP-1. Our studies indicate that macrophages from mammary tumor-bearing mice express higher levels of CHI3L1 compared to normal control mice and also secrete CCL2/MCP-1. We hypothesize that inhibition of CHI3L1 will suppress the production of CCL2/MCP-1 and enhance IFN-γ production in mammary tumor-bearing mice. One of the known ligands for CHI3L1 is chitin microparticle. Our in vitro studies of cultured splenocytes from normal and 5-week mammary tumor-bearing mice with chitin micro-particles revealed down-regulation of CHI3L1 and upregulation of IFN-γ. Therefore, it is expected that in vivo blocking of CHI3L1 with chitin microparticles will have a favorable anti-tumor response by inhibiting the production of angiogenic chemokines, metalloproteinase, MMP-9 and enhancing the production of IFN-γ. The results from these studies may provide new avenues for cancer treatment.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1339.
Abstract 1341: Early detection of tumor cells by innate immune cells leads to Treg recruitment through CCL22 production by tumor cells
Authors: Faget Julien , Biota Cathy , Bachelot Thomas , Gobert Michael , Dezutter-Dambuyant Colette , Treilleux Isabelle , Goddard-Leon Sophie , Blay Jean Yves , Caux Christophe , Menetrier-Caux Christine 
Published: February 2011

Abstract
We recently obtained evidences, in breast carcinoma, that regulatory T cells (Treg) localized within lymphoid aggregates, but not in the tumor bed, have a negative impact on patients’ survival. Immunohistochemical analysis on paraffin embedded sections of tumors demonstrated correlation between CCL22 production tumor cells and Treg infiltration thus identifying CCL22 as a key mediator of intratumoral Treg recruitment (Gobert M., Cancer Res vol 69, p2000-9, 2009). Herein we decipher the mechanisms regulating CCL22 production by tumor cells.
In vitro, human breast epithelial tumor cell lines secreted low CCL22 levels that were strongly increased in response to inflammatory signals (TNFα, IFNγ and IL-1β or their combination). Using an in vitro model we demonstrated that breast tumor cell lines (MCF-7, MDA-MB453, CLB-SAV, BT-474) but not immortalized normal breast epithelial cell line (Telma) secreted functional CCL22 in response to culture with PBMC or their supernatants. Addition of IL-1RA and anti-TNFα abrogated the CCL22 secretion demonstrating the importance of Il-1β and TNFα in CCL22 production. Depletion experiments demonstrated a major role of monocytes within PBMC in i) the induction of CCL22 and ii) the production of IL-1β and TNFα. However, co-culture of tumor cells with purified monocytes was not sufficient to reproduce the PBMC effects. The addition of rhIFNγ to tumor cell and monocyte co-cultures restored the CCL22 production by tumor cells and that of IL-1β by monocytes suggesting a role of IFNγ producing cells (T cells or NK cells) within PBMC.
Taken together, these results demonstrate a dialogue between monocytes, tumor cells and IFNγ producers (NK or T cells) leading, through monocyte-derived IL-1β and TNFα, to CCL22 production by tumor cells and Treg recruitment. These observations would suggest that early tumor cell detection by innate effectors (monocytes, NK) would trigger CCL22 production by tumor cells and not normal mammary epithelial cells leading to Treg recruitment as a mechanism to stop the anti-tumor immune reactivity.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1341.
Abstract 1344: TGFß, an inflammation and immune suppressor in tumor microenvironment and progression
Authors: Yang Li , Pang Yanli , Yan Hannah , Li Zhaoyang , Achyut BR 
Published: February 2011

Abstract
Alterations in TGFβ signaling have significant effects on tumor initiation and progression. TGFβ functions both as a tumor suppressor and as a tumor promoter. Most work so far to dissect mechanisms underlying this dual role of TGFβ has been largely focused on differential regulation of signaling pathways by tumor autonomous TGFβ signaling. Studies from our lab demonstrate that TGFβ significantly regulate inflammation in tumor microenvironment and host immune response. When TGFβ R2 receptor is deleted in mammary cancer epithelial cells, there was an increased inflammation and recruitment of Gr-1+CD11b+ myeloid cells, which leads to increased tumor invasion and metastasis. This infiltration of Gr-1+CD11b+ cells also results in increased abundance of TGFβ1 and metalloproteinase activity in tumors with Tgfbr2 deletion. Interestingly, Tumor-infiltrating Gr-1+CD11b+ cells exhibited significant elevated TGFß signaling including increased expression of RI and RII receptor, TGFß1 and TGFß3 ligands, as well as latent transforming growth factor ß binding protein when compared with normal myeloid cells. Genetic deletion of Tgfbr2 in myeloid cells significantly attenuated 4T1 breast carcinoma tumor growth and metastasis. This is accompanied with significantly increased IFNγ production in the lungs of tumor bearing mice. These data suggest that TGFß, the tumor suppressor, also functions as an inflammation and immune suppressor. TGFß signaling in host derived myeloid cells is an important mediator in tumor immune surveillance. This new understanding of TGFß in inflammation and immune response in the interface of tumor and host may provide insight information for TGFß switch from a tumor suppressor to a tumor promoter.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1344.
Abstract 1349: Ablation of E2f3 in macrophages reduces the incidence of lung metastasis
Authors: Trikha Prashant , Pena Clarissa , Sharma Nidhi , Reyes Andreas , Leone Gustavo 
Published: February 2011

Abstract
The tumor stroma is predominantly composed of cells of the immune system, one of them are the tumor-associated macrophages (TAMs). Tumor macrophages are recruited to the tumor in response to cytokines secreted by the tumor epithelial cells. TAMs secrete proteases into the extracellular matrix (ECM) that contributes to tumor cell intravasation. Rb-E2F axis represents one of the important pathways involved during cell cycle and is deregulated in number of cancers. E2Fs have distinct roles in the control of cell proliferation, apoptosis and differentiation pathways. We have previously shown that E2F are important downstream targets in CSF-1 signaling cascade that are involved in macrophage survival and proliferation. Present study is aimed at exploring the link between conditional ablation of E2f3 in TAM and its effect on lung metastasis using MMTV-PyMT mouse model of breast cancer. Ablation of E2f3 in the tumor macrophages resulted in a reduction of lung metastasis without affecting tumor onset or macrophage numbers. Microarray analysis of E2f3 deleted TAMs showed an up-regulation in expression of genes involved during metastasis. Our results show that E2f3 regulates the physiological processes in TAMs that inhibit lung metastasis.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1349.