bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2424: Interferon consensus sequence binding protein promotes epithelial to mesenchymal transition and cell motility in human osteosarcoma cells
Authors: Park Byung-Kiu , Sung Jee Young , Na Yoon Sook , Kim Yong Nyun 
Published: June 2012

Abstract
Interferon consensus sequence binding protein (ICSBP) is a regulatory factor induced by interferon gamma (IFN-γ) and a member of interferon regulatory family (IRF). ICSBP is mainly expressed in hematopoietic cell and regulates immune response and differentiation but its role in non-hematopoietic cells is largely unknown. Here we investigated a role of ICSBP in human osteosarcoma U2OS cell line. Basal level of ICSBP expression was low but was induced by interferon-γ in U2OS cells. In addition, induced ICSBP promoted U2OS cell proliferation. To further elucidate ICSBP functions in osteosarcoma cells, we generated the U2OS stable cell line that overexpresses ICSBP. ICSBP overexpressing cells grew faster compared with mock cells and showed morphological changes. ICSBP upregulated TGF-βRI expression resulting in activation of TGF-β signaling pathways. In addition, ICSBP expression altered cell morphology and increased cell adhesion and motility. Furthermore ICSBP increased vimentin expression but decreased ZO-1 and E-cadherin expression, which is EMT related phenomena. These motility and EMT related phenomena were inhibited by TGF-βRI inhibitor. Taken together, these findings indicate that ICSBP promotes EMT and cell motility via TGF-β pathways in U2OS cells.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2424. doi:10.1158/1538-7445.AM2011-2424
Abstract 2430: Aromatase expression inhibits anoikis and promotes bone metastasis of ERα positive breast cancer cells
Authors: Liu Zhao , De Mukhopadhyay Keya , Yu Lan , Sun Lu-Zhe 
Published: June 2012

Abstract
Aromatase is the rate-limiting enzyme that catalyzes the final step in estrogen biosynthesis. In postmenopausal women the ovary ceases to make estrogen. Although it has been shown that estrogen is produced locally in breast cancer (BCa) tissue of postmenopausal women for the proliferation and survival of ERα (+) BCa cells, there is little information on the role and the regulation of aromatase in breast cancer cells for their survival when they intravasate into the circulation where estrogen level is very low.
Human breast cancer CAMA-1 cell along with aromatase-transfected MCF-7 (MCF-7/Aro) and ZR-75-1 (ZR-75-1/Aro/CL10) cells were cultured in suspension to mimic circulating tumor cells. Interestingly, all the three ERα(+) BCa cell lines expressed more aromatase in suspension culture compare to the adhesion culture. Moreover both endogenous and transfected aromatase were upregulated in suspension culture. Additionally, a higher expression of ERα was also observed in suspension culture, which could increase the sensitivity of the breast caner cells to intracrine estrogen. We found that anoikis was shown to be inhibited by the supplementation of testosterone, which is converted to estradiol by aromatase. Conversely, addition of the aromatase inhibitor letrozole blocked the testosterone-induced anoikis inhibition. The increase of pro-apoptotic protein BAX and BAD were observed in suspension culture, while the treatment of estrogen inhibited the expression of BAX and BAD in both adhesion culture and suspension culture. More interestingly, mice with intracardiacally inoculated ZR-75-1/Aro cells presented distant bone metastasis in the mandible and tibiae/femora after 2-weeks of inoculation without estrogen supplement, while the control ZR-75-1 cells were incapable of forming metastasis without estrogen. Our findings provide an important foundation for future investigation on how hormone-dependent BCa cells survive in circulation during the process of metastasis.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2430. doi:10.1158/1538-7445.AM2011-2430
Abstract 2450: Resistance of CD44+ hepatocellular carcinoma cancer stem cellsto immune effector responses
Authors: Wan Shanshan , Vatan Linda , Simeone Diane M. , Kryczek Ilona , Zou Weiping , Welling Theodore H. 
Published: June 2012

Abstract
Hepatocellular carcinoma (HCC) is a common cause of cancer-related deaths worldwide. There is little therapy for advanced disease and recurrence rates can be as high as 50% following resection. Evidence in several tumor types suggests that cancer stem cells (CSCs) contribute to tumorigenicity, therapeutic resistance and recurrence, however the HCC CSC phenotype remains to be completely defined. HCC recurrence is influenced by the degree of immune response in the tumor microenvironment. Therefore, we aimed to characterize HCC-CSCs phenotype and investigate the interaction between CSCs and immune cell subsets.
To identify a dominant CSC population in HCC, we examined several putative CSC markers, including CD44, CD90, CD133 and EpCAM on primary human resected HCCs (n=6), HCC xenografts (n=2), and HCC cell lines (n=3) using flow cytometry. Cells from all sources consistently showed discrete populations of CD44+ cells (2-40%), while other common CSC markers showed significant heterogeneity. CD44+ cells isolated from HCC xenografts or HepG2 cells by fluorescence-activated cell sorting (FACS) demonstrated enhanced tumorigenic potential with as little as 100 cells implanted into NOD-SCID/IL-2Rgnull mice compared to no tumor from 100 CD44− cells. CD44+ cells were also able to produce heterogenic tumor mass in vivo. Moreover, CD44+ cells demonstrated increased sphere forming capacity in serum free media (2 fold, p&lt;0.05), and increased resistance to the chemotherapeutic agents cisplatin and doxorubicin in vitro. Additionally, CD44+ HCC cells were resistant to effector cytokines such as IFNγ and TNFα and effector responses during co-culture with anti-CD3/anti-CD28 activated T cells from healthy donor PBMCs. CD44+ HCC cells had 2-fold increased expression of B7-H1, a co-inhibitory molecule for T cells, when compared to non-CSCs during exposure to activated T cells or effector cytokine IFNγ, suggesting a possible mechanism of resistance to immune effectors in the HCC microenvironment.
In conclusion, CD44 discriminates for the HCC CSC as evidenced by CD44+ subset demonstrating enhanced tumorigenicity, sphere forming capacity and resistance to chemotherapeutic agents. CD44+ CSC are also resistant to activated T cells and effector cytokines suggesting that microenvironmental factors related to immune response may be important for HCC recurrence or progression.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2450. doi:10.1158/1538-7445.AM2011-2450
Abstract 2462: Effects of KRASG12D and P53 oncogenes on pancreatic cellular plasticity
Authors: Chen Jeff , Contino Gianmarco , Gurumurthy Sushma , Bardeesy Nabeel 
Published: June 2012

Abstract
Pancreatic Ductal Adenocarcinoma (PDAC) is fourth most common cause of cancer death in the United States. Improved understanding of the early stages of this cancer could enable interventions at a time where therapies will be most effective. The cells that give rise to PDAC have not been fully defined, although experimental studies have revealed considerable plasticity for different pancreatic cell types to interconvert their cellular identities. Notably, recent studies have shown that a subpopulation of pancreatic centroacinar cells_marked by the expression of Aldehyde dehydrogenase (ALDH) -has progenitor-like properties with the potential to give rise to both exocrine and endocrine lineages. Here, we used published protocols (Rovira et al., Proc Natl Acad Sci U S A. 2010 Jan 5;107(1):75-800) to isolate ALDH+ centroacinar cells and examined the effect of the common gene mutations found in PDAC on the clonogenic growth of the cells. We found that activating KRAS mutations and p53 inactivation both significantly enhanced the growth of ALDH+ cells as spheroids. These cells represent a potentially powerful tool to elucidate mechanism of transdifferentiation in the pancreas and may help to more fully define how key oncogenic mutations drive PDAC initiation.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2462. doi:10.1158/1538-7445.AM2011-2462
Abstract 2466: RON receptor tyrosine kinase as a targeting moiety for pancreatic cancer stem-like cells by antibody directed immunoliposomes for enhanced cytotoxicity
Authors: Padhye Snehal , Wang Ming-Hai 
Published: June 2012

Abstract
Pancreatic adenocarcinoma (PAC) is a malignant disease characterized by metastasis and chemo-resistance. Accumulated evidence has suggested that PAC malignancies arise due to functional presence of cancer stem cells that have high potential for self renewal, differentiation, and resistance to cytotoxic agents. Currently, therapeutics targeting PAC stem cells are not available. The study in this project describes a novel strategy and potential therapeutics targeting PAC stem cells for enhanced cytotoxicity. PAC stem like cells (PSLC) were obtained from human L3.6pl pancreatic cancer line under stem cell culture conditions. These cells show a typical sphere-like morphology in suspension and re-differentiate into epithelial appearance when subjected to serum inclusive adherent conditions. PSLC express transcription factor Bmi-1, a unique self-renewal marker, Aldh-1a, a metabolic enzyme expressed in stem-like cells, and cell-surface markers including CD24, CD44, and ESA as evidenced by Western blot and flow cytometry analyses. PSLC also displayed a phenotype characterized as epithelial to mesenchymal transition. Analysis of a panel of receptor tyrosine kinases has revealed that expression of EGFR, VEGFR, and MET was significantly reduced in PSLC. In contrast, RON receptor tyrosine kinase expression was sustained, which provides the molecular basis for antibody-directed approach for targeting PSLC. To achieve this goal, Zt/c9 monoclonal antibody was post-inserted onto doxorubicin liposomes to form anti-RON immunoliposomes (Zt/c9-Dox-IL). In vitro analysis indicated that; a) Zt/c9 was highly effective in inducing receptor internalization, which facilitates intracellular delivery of chemoagents; b) Zt/c9-Dox-IL was effective in killing Panc 0327 and L3.6pl PAC cells. An average of 7 fold decrease in IC50 value was obtained compared to control Dox-IL inserted with mouse IgG (mIgG-Dox-IL); and c) Zt/c9-Dox-IL displayed increased cytotoxicity against PSLC with the IC50 at 8 µM compared to 69 µM for mIgG-Dox-IL. In conclusion, PSLC enriched from L3.6pl cells display a phenotype similar to cancer stem cells with properties of increased self renewal and EMT. RON expression was maintained in PSLC, which was used as the drug delivery moiety for enhanced cytotoxicity. Increased PSLC cytotoxicity by Zt/c9-Dox-IL suggests that antibody-directed RON targeted delivery of cytotoxic agents is a rational approach for targeting PSLC to achieve enhanced cytotoxicity.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2466. doi:10.1158/1538-7445.AM2011-2466
Abstract 2468: ATM signaling to mTORC1 in response to DNA damage independent of AMPK activation
Authors: Alexander Angela , Kim Jinhee , Walker Cheryl L. 
Published: June 2012

Abstract
When DNA becomes damaged either as a result of endogenous processes or exposure to radiation or chemicals, the DNA damage response is rapidly engaged. DNA damage response pathways have been well-characterized at the molecular level, and are known to involve a large network of proteins that trigger cell cycle checkpoints to allow time for DNA repair or trigger apoptosis via p53-dependent mechanisms if the damage is too severe to be repaired. However in addition to these classic damage responses, our previous work on ROS-induced pathways indicated that an additional aspect of the cellular damage response to many types of damage or stress could be induction of autophagy via repression of mTORC1.
We found previously that ROS could activate ATM in the cytoplasm, independently of the DNA damage produced by ROS, and subsequently activate the LKB1-AMPK energy-sensing pathway to activate TSC2 and repress mTOR, therefore inducing autophagy. We next asked whether a similar pathway could be induced in response to DNA damage, since there have been a few reports of AMPK activation by DNA damage in some cell lines, and ATM has been shown to activate AMPK via both LKB1-dependent and LKB1-independent mechanisms.
In a panel of cancer cell lines, including MCF7 breast carcinoma cells and SKOV3 ovarian carcinoma and other cells such as MEFs and HEK293, we profiled the signaling events in response to classic double-strand break agents such as etoposide, ionizing radiation or radiomimetic neocarzinostatin, as well as the intrastrand crosslinking agent cisplatin. In a cell-line and damage-specific manner, mTORC1 could be repressed, but unlike the previously identified ROS-induced signaling pathway, AMPK was not activated. In addition, in contrast to the rapid ROS-induced signaling pathway, DNA damage induced mTORC1 suppression occurred over a period of hours (6-24 hours), suggesting that additional mechanisms may be involved in signaling to mTORC1. Using Tsc2-deficient MEFs, we demonstrated that mTORC1 suppression requires TSC2, a negative regulator of mTORC1. This dichotomous response between ROS-induced mTORC1 suppression via AMPK activation of TSC2, and DNA damage, which does not require AMPK, indicates that mTORC1 regulation by DNA damage is complex and context-dependent, which may have implications for understanding mechanisms of action of DNA damaging cancer therapeutics.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2468. doi:10.1158/1538-7445.AM2011-2468
Abstract 2477: RBM3 prevents radiation-induced mitotic catastrophe by promoting anaphase
Authors: Moran Elizabeth , Ramalingam Satish , Subramaniam Dharmalingam , Moriasi Cate , Jensen Roy A. , Anant Shrikant 
Published: June 2012

Abstract
Deregulation of tumor suppressor and oncogenes is a key event in tumorigenesis and enhanced radioresistance. Post-transcriptional control of mRNA stability and translational control are important mechanisms by which these genes may be deregulated. We have previously demonstrated that RBM3, a glycine-rich RNA binding protein, is upregulated in cancers. Overexpression of RBM3 also transformed normal cells and led to tumor formation in vivo, suggesting that the protein is a protooncogene. Conversely, knockdown of RBM3 in cancer cells reduced tumor growth, in part due to cells undergoing mitotic catastrophe. Mitotic catastrophe is a common form of radiation-induced cell death. We are currently seeking to determine whether ectopic overexpression of RBM3 confers radioresistance. Our preliminary findings show increased survival of RBM3-overexpressing cells and a decrease in radiation-induced G2/M arrest. Additionally, RBM3 overexpression led to decreased expression level and activity of cellular machinery promoting apoptosis. Conversely, proteins related to cellular survival were upregulated in RBM3-overexpressing cells. The CDC20-APC complex protects cells from mitotic catastrophe by allowing the cells to transition successfully through anaphase. Inhibition of CDC20 therefore results in mitotic catastrophe. We recently observed that RBM3 overexpression resulted in CDC20 upregulation and increased the degradation of proteins regulated by the APC-CDC20 complex. Additionally, CDC20 activator Aurora Kinase B, but not Aurora Kinase A, was upregulated while CDC20 inhibitors Bub1b and Bub3 were downregulated. Preliminary findings would therefore suggest that RBM3 protects cells from mitotic catastrophe and does so in part by enhancement of anaphase. These findings imply that RBM3 confers radioresistance in part through upregulation of CDC20 and its enhancers and downregulation of its inhibitors, thereby preventing mitotic catastrophe.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2477. doi:10.1158/1538-7445.AM2011-2477
Abstract 248: Control of prostate tumor growth and centriole amplification by antizyme and antizyme inhibitor
Authors: Olsen Rachelle R. , Chung Ivy , Zetter Bruce R. 
Published: June 2012

Abstract
The endogenous antizyme inhibitor (AZI) is best characterized for its role in regulating polyamine homeostasis. Polyamines are organic cations synthesized by the enzyme ornithine decarboxylase (ODC), a protein which is negatively regulated and targeted for proteasomal degradation by antizyme (AZ). AZI is a potential oncogene which promotes cell growth not only by inhibiting antizyme (AZ) activity, but also by releasing ODC from AZ-mediated degradation. High levels of ODC and polyamines are associated with numerous types of neoplastic transformation, and the genomic region including AZI is frequently amplified in tumors of the ovary and prostate. To determine whether AZI functionally promotes prostate tumor growth, we made PC3M-LN4 (human) and AT6.1 (rat) cancer cell lines stably expressing AZI shRNA. AZI knockdown was confirmed by western blot and RT-PCR. To examine the ability of these cells to form tumors in vivo, 1×106 cells were injected subcutaneously into nude mice either with (PC3M-LN4) or without (AT6.1) Matrigel. Tumor growth was measured two times per week by caliper. Cells in which AZI levels had been knocked down by shRNA formed significantly smaller tumors in vivo, and had significantly smaller end tumor weights. These results suggest that not only does AZI promote tumor growth, but also that AZI may be a novel and valid therapeutic target for cancer treatment.
In addition to their effects on cell proliferation, previous studies in our laboratory have shown that both AZI and AZ localize to centrosomes and are important for controlling centrosome duplication. Centrosome amplification is a frequent and early event in tumorigenesis. We found that overexpression of AZI and knockdown of AZ both result in cells with daughter centriole amplification due to abnormal centriole synthesis. To gain insight into the mechanism by which AZ and AZI modulate centriole synthesis, we are currently analyzing whether proteins that regulate centrosome duplication interact with either AZI or AZ. We are also using Tet-inducible overexpression vectors to monitor the effect of increased AZ or AZI levels on centriole amplification, and exploring how localization of these proteins to the centrosome contributes to the centrosome amplification phenotype. These studies provide a much greater understanding of AZI function, and suggest that high AZI levels may contribute to tumorigenesis both by promoting cell growth and inducing centrosome amplification.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 248. doi:10.1158/1538-7445.AM2011-248
Abstract 2493: Capsaicin, a novel radiosensitizer, acts via a TRPV6 mediated mechanism
Authors: Venier Natalie A. , Colquhoun Alexandra J. , Sasaki Hiroshi , Loblaw Andrew D. , Fleshner Neil E. , Klotz Laurence H. , Venkateswaran Vasundara 
Published: June 2012

Abstract
Radiosensitizing agents sensitize cells to the lethal effects of ionizing radiation (IR). This permits use of lower doses of radiation to achieve equivalent cancer control thereby minimizing adverse effects to normal tissues. Given their lack of toxicity compounds occurring naturally in the diet make ideal potential radiosensitizing agents.
Capsaicin, a compound found in the Capsicum sp. of plants, is a widely consumed food additive in areas with low PCa incidence. Traditionally capsaicin is used to treat chronic pain syndromes; however, recently evidence using in vitro PCa models describes its anti-carcinogenic potential. The transient receptor potential vanilloid-receptor (TRPV)-1 and TRPV6 cation selective channels are thought to be partly responsible for mediating these effects. TRPV-1 and TRPV-6 expression is up-regulated in PCa tissue correlating directly with increasing tumor grade. This suggests TRPV1 and/or TRPV6 may be potential therapeutic targets for capsaicin mediated interventions in PCa patients.
As IR and capsaicin both promote apoptosis and inhibit cell cycle progression in vitro we hypothesize an at least additive effect of combining these two therapies.
Using clonogenic assays we assessed the effect of ionizing radiation (1-8 Gy) and/or capsaicin (1-10μM) on colony formation rates in 4 human PCa cell lines (LNCaP, PC3, PC3AR2, DU145). Proliferative, apoptotic, TRPV-6 protein markers were assessed using Western blot analyses.
Exposure of cells to capsaicin (1-10μM) or IR (1-8Gy) caused significant dose-dependent inhibition of colony formation (p&lt;0.001). Combining capsaicin with IR resulted in further significant inhibition of colony formation rates (P&lt;0.001). Western blot analyses showed LNCaP cells treated with capsaicin and/or IR to have increased expression of pro-apoptotic proteins BAX and Bad, tumor-suppressor proteins p21 and p27 and reduced androgen-receptor. Additionally, capsaicin monotherapy caused a dramatic alteration in TRPV1 and TRPV6 expression.
These studies confirm the radiosensitizing capacity of capsaicin in PCa cells in vitro. Ongoing studies using are further delineating the mechanism of interaction of these treatment modalities.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2493. doi:10.1158/1538-7445.AM2011-2493