bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3405: Caveolin-1 modulates the metastatic ability of Ewing's sarcoma
Authors: Sainz-Jaspeado Miguel , Lagares-Tena Laura , Lasheras Jaime , Navid Fariba , Rodriguez-Galindo Carlos , Mateo-Lozano Silvia , Notario Vicente , Sanjuan Xavier , del Muro Xavier Garcia , Fabra Angels , Tirado Oscar M. 
Published: February 2011

Abstract
Metastasis is the final stage of tumor progression and is thought to be responsible for up to 90% of deaths associated with solid tumors. Caveolin-1 (CAV1) regulates multiple cancer-associated processes including cellular transformation, tumor growth, cell death and survival, multidrug resistance, angiogenesis, cell migration and metastasis. Although CAV1 was previously identified as a metastasis-associated gene that is a transcriptional target of EWS/FLI1 as well as an important determinant of Ewing's sarcoma family of tumors (ESFT) malignant phenotype, the possible involvement of CAV1 in regulating the ability of ESFT to metastasize has not been established. Therefore, in the present study we tested the hypothesis that CAV1 modulates the metastatic ability of ESFT cells. First, we analyzed the expression of CAV1 by immunostaining a tissue microarray (TMA) containing 43 paraffin-embedded ESFT tumors with known EWS translocations. Even though no evidence was found for a significant association between CAV1 expression with stage, size or tumor site, all metastatic samples (10/10) had significantly high CAV1 expression, suggesting that high CAV1 content makes it easier for ESFT cells to metastasize. To determine the effect of CAV1 on the migratory and invasive capabilities of ESFT cells, we knocked down CAV1 expression in TC252 and A673 cells by stably transfecting a previously validated shRNA construct. In vitro, wound healing and transwell migration and invasion assays showed that, in both cell lines. CAV1 knocked-down cells migrated significantly less (p≤0.01) than parental and vector-transfected control cells. Moreover, control transfected A673 cells introduced into balb/c nude mice by tail vein injection strongly colonized the lungs. In contrast, about 40% of animals injected with low CAV1 cells had no incidence of metastasis to any organ, and the other 60% suffered a significant delay in lung colonization (P=0.0005). These data demonstrate that CAV1 plays a key role in regulating the ability of ESFT cells to metastasize. Ongoing experiments are designed to elucidate the CAV1-regulated signalling pathways responsible for the development of ESFT metastases.
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 3405.
Abstract 3411: Targeting of EWS-FLI1 with small molecule YK-4-279 reduces xenograft growth by disruption of disordered protein-protein interactions
Authors: Toretsky Jeffrey A. , Erkizan Hayriye V. , Kong Yali , Merchant Melinda , Barber-Rotenberg Julie S. , Brown Milton L. , Üren Aykut 
Published: February 2011

Abstract
Introduction: EWS-FLI1 oncoprotein is expressed as a result of a tumor-specific translocation that occurs in patients with Ewing's Sarcoma. Development of strategies to therapeutically target EWS-FLI1 revealed its significant intrinsically disordered regions. The intrinsically disordered regions enhance protein-protein interactions while presenting an opportunity for small molecule targeting. We hypothesized that a small molecule could bind to EWS-FLI1 and prevent a key protein-protein interaction with RNA Helicase A (RHA) leading to decreased cell growth. Methods: Small molecule library screening was performed using surface plasmon resonance. Chemical optimization followed by fluorescence polarization enhanced and confirmed compound binding to EWS-FLI1, respectively. Testing of compounds included co-immunoprecipitation, cell growth, caspase-3, and xenografts. Results: A library of 3000 compounds (NCI, DTP) was screened for EWS-FLI1 binding. NSC635437 had an RUactual: RUtheorhetic of 0.9 and was chosen for further evaluation based upon potential for chemical derivatization. One optimized compound, YK-4-279, significantly reduced the protein-protein interaction between EWS-FLI1 and GST-RHA(647-1075). SPR measurement of the KD was 9.48 microM for the affinity of YK-4-279 with EWS-FLI1. YK-4-279 has an IC50 of 1 microM for a series of ESFT cell lines, while cell lines that lack EWS-FLI1 are 10-30 fold more resistant to the compound. YK-4-279 reduced the growth of Ewing's Sarcoma xenografts while not affecting the growth of PC3 prostate tumors. PONDR analysis of EWS-FLI1 and RHA indicate that their interaction is occurring in an ordered-disordered transition region of RHA. Conclusions: The lead compound derivative YK-4-279 demonstrates that the EWS-FLI1/RHA interaction can be blocked with a detrimental effect on Ewing's Sarcoma cells both in vitro and in vivo. These findings both validate the interaction of EWS-FLI1 with RHA as an oncogenic target and provide a lead compound for therapeutic development. Additional studies are underway to evaluate the contributions of the disordered regions to small molecule binding and developing strategies of optimization.
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 3411.
Abstract 3432: A green tea polyphenol epigallocatechin-3 gallate specifically targets tumor-associated endothelial cells
Authors: Hida Yasuhiro , Ohga Noritaka , Muraki Chikara , Akiyama Kousuke , Kondoh Miyako , Maishi Nako , Kurosu Takuro , Ishikawa Shuhei , Hirata Naoya , Shindoh Masanobu , Hida Kyoko 
Published: February 2011

Abstract
A green tea polyphenol, epigallocatechin-3 gallate (EGCG) suppresses tumor growth in vivo. We investigated mechanisms of specific tumor angiogenesis inhibition using tumor-associated endothelial cells (TECs), peripheral blood-derived ECs, and normal endothelial cells (NECs). TECs were isolated and cultured from human tumor xenografts in nude mice. Peripheral blood-derived ECs were isolated from peripheral blood of nude mice. EGCG suppressed migration of TECs and peripheral blood-derived ECs. EGCG also inhibited the phosphorylation of Akt in TECs and peripheral blood-derived ECs. The PI3K inhibitor, LY294002 blocked the migration of TECs induced by VEGF. Furthermore, VEGF-induced mobilization of CD133/VEGFR-2 double-positive cells into circulation was inhibited by EGCG. MMP-9 in the bone marrow is involved in mobilizing bone marrow-derived VEGFR-2 positive cells into peripheral circulation. Expression of MMP-9 mRNA was suppressed in bone marrow stromal cells by EGCG. In vivo model, EGCG reduced melanoma growth. Our study showed that EGCG specifically inhibits TEC and circulating EC through PI3K in EC and MMP-9 expression in bone marrow stroma. EGCG is a promising angiogenesis inhibitor for cancer therapy.
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 3432.
Abstract 3447: Identification of Gastric Cancer-Specific Helicobacter Pylori Genes Using Suppression Subtractive Hybridization
Authors: Gong Yue-hua , Jun Liu , Yuan Yuan 
Published: February 2011

Abstract
Helicobacter pylori (H. pylori), a microaerophilic Gram negative bacterium, is known to cause chronic gastritis, peptic ulcer, and gastric cancer. Genes that are present in certain isolates may determine strain-specific traits such as drug resistance. In order to understand the pathogenic mechanisms of gastric diseases, identify the molecule markers of the diseases associated with H.pylori strains, and provide clue for the target treatment of H. pylori related diseases, a subtracted DNA library was constructed from a gastric cancer-associated H. pylori strain and a superficial gastritis-associated H. pylori strain by suppression subtractive hybridization. Differentially expressed genes were identified by dot blot hybridization and DNA sequencing. Twelve high copy genes and 9 low-copy genes were found in gastric cancer-associated strain compare to superficial gastritis strain. These differentially expressed genes were confirmed by PCR analysis of bacteria isolates. Interestingly, PPIase was detected positively in 13 out of 26 H pylori strains derived from gastric cancer patients. In contrast, less than 24% of H pylori strains from superficial gastritis showed positive. Our results suggest that PPIase may represent a novel marker and potential therapeutic target for gastric 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 3447.
Abstract 345: Prostaglandin receptors differentially regulate prostate cancer growth: A novel treatment target
Authors: Huang Hosea F. , Shu Ping , Murphy Thomas F. , King Sherita , Wright Chris , Jordan Mark L. 
Published: February 2011

Abstract
INTRODUCTION AND OBJECTIVE: Prostaglandin E2 (PGE2) acts through a series of distinct prostanoid receptors, EPR 1-4. Since PGE2 is implicated in prostate cancer (CaP) tumorigenesis and metastasis, we hypothesized that EP receptor expression may influence CaP growth.
METHODS: 27 consecutive radical prostatectomy specimens were assessed by immunohistochemistry (IHC) for EPR expression and compared with normal human prostate epithelium (NP) from the same specimen as control. As a corollary, the expression of EP receptors in both normal (PrEC, PWR1E and PZ-HPV7) and CaP cells (LNCaP, PC3 and CA-HPV10) were assessed by RT-PCR and Western blot. The functional significance of EPR was assessed by growth of malignant and benign cell lines in vitro after siRNA EPR knockdown. All studies were approved by the local institutional review board (IRB) and all in vitro experiments performed a minimum of 3 times.
RESULTS: EP1, EP2, EP3 and EP4 receptors were detected by IHC in all NP clinical specimens. Compared with NP, EP4 and EP2 were over-expressed in 74% (20/27) and 63% (17/27) of CaP specimens, respectively; in contrast, EP3 expression was reduced in 93% (25/27) clinical samples (Figure). EP1 showed no specific differential expression pattern. Western blot showed increased EP4 but reduced EP3 in CaP lines (CA-HPV10, LNCaP and PC3) compared with NP lines; EP2 and EP4 knockdown significantly suppressed whereas EP3 knockdown stimulated in vitro growth of CA-HPV10 vs PZ-HPV7 cells. Expression of Runx 2 and MMP9, (known to contribute to CaP metastatic potential) was also reduced after EP2 and EP4 knockdown in CaP cells.
CONCLUSION: We observed EP4 and EP2 over-expression and reduced EP3 expression in 27 consecutive resected CaP specimens and in 6 representative cell lines. These observations were corroborated by the effects of EP4, EP2 and EP3 knockdown on tumor cell growth in vitro. These data suggest that EP receptor subtypes may regulate CaP growth which may represent a novel therapeutic approach.
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 345.
Abstract 3452: Role of P-glycoprotein in carcinogenesis
Authors: Wang Lihua , Jiang Weiwu , Moorthy Bhagavatula , Kondraganti Sudha Rani 
Published: February 2011

Abstract
Cancer accounts for nearly one-quarter of deaths in the United States, exceeded only by heart diseases. Polycyclic aromatic hydrocarbons (PAHs) are commonly found in our environment and appear to be carcinogenic by genotoxic mechanisms. Several studies show that over-expression of P-glycoprotein (Pg-p, coded by mdr1) is associated with the development of various cancers. High expression of the mdr1 gene has been reported in many human cancers such as in breast, liver, colon, kidney and brain. Many molecular and cellular studies have revealed the ability of dietary phytochemicals in vegetables and fruits to reduce the risk of cancer. The abundant and inexpensive dietary phytochemicals are being explored as Pg-p modulators in cancer chemoprevention and chemotherapy.
In the present study, we investigated the role of P-gp in cancer development. We also studied whether the inhibition of P-gp function could reduce the development of cancer. The wild type (C57BL/6J) mice were exposed to the environmental PAH, 7, 12-dimethylbenz(a)anthracene (DMBA) and dietary phytochemicals, alone and in combination. The hepatic and mammary gene expressions of P-gp, Pregnane X receptor (PXR), and CYP3A11 were analyzed. The environmental PAHs induced hepatic and mammary expressions of P-gp and associated genes in mice, compared to controls. Administration of dietary phytochemicals inhibited the P-gp expression significantly. Induction of specific DNA adducts were also observed in hepatic and mammary tissues of mice treated with PAHs and phytochemicals.
These studies show a potential for development of dietary phytochemicals as Pg-p modulators in chemoprevention and chemotherapy of human cancers.
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 3452.
Abstract 346: Aspirin blocks EGF responsiveness in ovarian cancer cells
Authors: Cho May , Khabele Dineo , Son Deok-Soo 
Published: February 2011

Abstract
Many ovarian cancers overexpress epidermal growth factor receptor (EGFR). EGFR over-expression in ovarian cancer has been associated with poor prognosis. EGFR inhibitors alone do not produce positive clinical results in ovarian tumors that lack a tyrosine kinase mutation or over-express EGFR. This suggests that downstream signaling pathways remained active. In other tumors, efficacy of EGFR inhibitors is improved with combination therapy . Recent evidence suggests that human epithelial ovarian cancers express elevated levels of COX-1, indicating COX-1 is a potential target for therapy. Aspirin (acetylsalicylate, ASA) is a more selective COX-1 inhibitor and is also known to have anti-tumor and anti-angiogenic properties. Our objective was to investigate the effects of ASA on EGF-induced ovarian cancer cell growth. ASA inhibited cell proliferation induced by EGF with a dose dependent manner in COX-1 positive OVCAR-3 ovarian cancer cells. In particular, ASA decreased phosphorylated Akt and Erk activated by EGF. Furthermore, we made COX-1 expressing cell line (SKCOX-1) by stably transfecting COX-1 expression vector into COX-1 negative SKOV-3 cells. SKCOX-1 cells were more responsive to ASA compared to cells transfected with pcDNA-3 (SKpcDNA). Taken together, ASA inhibits proliferation of COX-1 positive ovarian cancer cells by blocking phosphorylation of Akt and Erk, probably potentiating the efficacy to treat ovarian cancer.
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 346.
Abstract 3462: A DNA methyltransferase inhibitor and all-trans retinoic acid reduce oral cavity carcinogenesis induced by the carcinogen 4-nitroquinoline 1-oxide
Authors: Tang Xiaohan , Albert Martin , Scognamiglio Theresa , Gudas Lorraine 
Published: February 2011

Abstract
The transcriptional silencing of some cell cycle inhibitors and tumor suppressors, such as p16 and RARβ2, by DNA hypermethylation at CpG islands is commonly found in human oral squamous carcinoma cells. We examined the effects of the DNA methyltransferase (Dnmt) inhibitor 5-Aza-2′-deoxycytidine (5-Aza, 0.25 mg/kg body weight), all-trans retinoic acid (RA, given at 100 μg/kg body weight and 1 mg/kg body weight, respectively), and the combination of 5-Aza and the low dose RA on murine oral cavity carcinogenesis induced by the carcinogen 4-nitroquinoline 1-oxide (4-NQO) in a mouse model. All the drug treatments were performed for 15 weeks after a 10-week 4-NQO treatment. Mice in all drug treatment groups showed decreases in the average numbers of neoplastic tongue lesions. The combination of 5-Aza and RA effectively attenuated tongue lesion severity. While all drug treatments limited the increase in the percentage of PCNA positive cells and the decrease in the percentage of p16 positive cells caused by the 4-NQO treatment in mouse tongue epithelial regions without visible lesions and in the neoplastic tongue lesions, the combination of 5-Aza and RA was the most effective. Collectively, our results show that the combination of a DNA demethylating drug and RA has potential as a strategy to reduce oral cavity cancer in this 4-NQO model.
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 3462.
Abstract 347: Inhibition of ERK1/2 can sensitize human malignant mesothelioma cells and tumors to doxorubicin
Authors: Shukla Arti , Hillegass Jedd M. , MacPherson Maximilian B. , Beuschel Stacie L. , Heintz Nicholas H. , Vacek Pamela M. , Pass Harvey I. , Carbone Michele , Testa Joseph R. , Mossman Brooke T. 
Published: February 2011

Abstract
Malignant mesothelioma (MM) has a poor prognosis because of its resistance towards different drugs. Extracellular signal regulated kinase (ERK) family is known to have important roles in tumorigenesis and drug resistance. Here we show that Doxorubicin (Dox) treatment activates ERK1/2 in different MM lines. Activated ERK1/2 play a significant role in cell survival as inhibition of ERK1/2 by U0126 in the presence of Dox results in significantly enhanced cell killing. We show here using small molecule inhibitor and RNA silencing approaches that ERK1/2 inhibition sensitizes human MM cells to Dox treatment. ERK1/2 inhibition by U0126 significantly inhibited certain important drug resistance and proapoptotic genes in human MM cells as measured by PCR Array using human drug resistance and metabolism template. MM cell lines stably transfected with shERK1 or shERK2 exhibited significant increases in the accumulation of Dox and decreases in the cell viability when treated with Dox as compared to shCon line. Microarray analysis performed on stable shERK1 and shERK2 lines showed more than 2 fold inhibitions in selected ATP binding cassette genes, which may be responsible in part for increased Dox accumulation and sensitivity. Finally, subcutaneous injection of stable human MM lines inhibited for ERK1 or ERK2 into SCID mice showed that inhibition of ERK1/2 sensitizes in vivo tumors to Dox. These studies demonstrate a key role of ERK1/2 in MM tumor drug resistance. This work is supported by National Cancer Institute grant P01CA114047 and VCC/LCCRO grant.
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 347.
Abstract 3496: SYK inhibition results in increased sensitivity of OVCAR-3 cells to paclitaxel
Authors: Sultan Aya , Wang Cindy Y. , Duran George E. , Francisco E. Brian , Berek Jonathan S. , Sikic Branimir I. 
Published: February 2011

Abstract
In order to identify novel drug targets in ovarian cancers, we examined our ovarian cancer gene expression microarray data for expression of genes in the tyrosine kinase family. The spleen tyrosine kinase (SYK) gene was expressed in 73% of 55 ovarian cancer specimens, compared to 26% of 60 breast cancer specimens. Previous studies established the role of SYK in lymphocyte development, immune cell activation, and tumor progression. We found SYK to be expressed in 6 of 10 ovarian carcinoma cell lines. Among its many targets, SYK can bind microtubules and other molecules associated with the cytoskeleton. Because of this ability, we studied the relationship of SYK expression to cellular sensitivity to taxanes. We focused on the OVCAR-3 cell line, which was one of the highest SYK-expressing cell lines, to elucidate the potential effects of SYK on taxane sensitivity. Our results demonstrate that knockdown of SYK expression by siRNA resulted in a one log-fold increased sensitivity of OVCAR-3 cells to the taxane, paclitaxel. Furthermore, this effect was durable, as knockdown of SYK and sensitization to paclitaxel persisted over 128 hours. The potential effects of SYK on tubulin polymerization are currently being investigated. We will evaluate potential upstream and downstream targets to elucidate the pathway(s) responsible for SYK effects and determine whether SYK levels contribute to tumor resistance to chemotherapeutic agents. Understanding the growth signals in drug sensitive and resistant ovarian cancer cell lines and tumor samples may eventually lead to new therapeutic approaches for ovarian cancers.
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 3496.