bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 804: Class II transactivator (CIITA) transcription is reduced by the ER-E2 signaling pathway in breast cancer cells
Authors: Mostafa Ahmed , Codner Dianne , Lewis Christa , Hirasawa Kensuke , Christian Sherri , Steimle Viktor , Drover Sheila 
Published: June 2012

Abstract
The immune response is regulated by the interaction of CD4+T-cells with human leukocyte antigen class II (HLA-II). HLA-II genes code for HLA-DR that display peptides from antigens, which have undergone proteolysis in the endocytic pathway. Peptide loading of HLA-DR molecules also requires the co-chaperones; Invariant chain (Ii) and HLA-DM. Regulation of HLA-II occurs mainly at the transcription level, through interaction of transcription factors with the class II transactivator (CIITA). We previously reported that discordant expression of HLA-II in breast cancer associated with decreased estrogen receptor (ER) levels and younger age at diagnosis, suggesting that the estrogen-ER signaling pathway is implicated in regulating HLA-II in breast carcinoma cells. Moreover, using an experimental model of ER+ and ER− breast cancer cell lines, we found that estradiol (E2) augmented expression in the ER− cell line but decreased expression in the ER+ transfectant. To address whether ER and E2 interfere with CIITA expression, we performed Western blotting and quantitative real-time PCR in the same experimental cell system. CIITA expression was markedly reduced in ER+, but not in ER− cells; furthermore, CIITA inversely correlated with ER levels. CIITA promoter activity was analysed using a luciferase reporter gene construct in cell lines, treated or not with E2 and/or ICI 182,780 (ER antagonist). CIITA luciferase activity was reduced in ER+ cells and was further inhibited by E2 and was restored by ICI. This suggests that ER may be recruited to the CIITA promoter and indirectly interfere with transcription of HLA-II genes. We further analyzed HLA-II in a wild type ER+ line, MCF-7, which was stimulated with IFN-γ or stably transfected with CIITA. HLA-DR surface expression, ascertained by flow cytometry, was upregulated in cells grown in E2-depleted medium. Western blotting confirmed that ER degradation by ICI in MCF-7 correlated with up regulation of CIITA and HLA-II. In aggregate, these results indicate that the E2-ER pathway interferes with CIITA and HLA-II expression. Investigations such as this should improve our understanding of how ER and estrogen modulate the antigen presentation capabilities and immune recognition of breast cancer 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 804. doi:10.1158/1538-7445.AM2011-804
Abstract 806: Anti-tumor effects of low temperature whole body hyperthermia on human bladder cancer cells in vivo
Authors: Yamamoto Yutaka , De Velasco Marco A. , Wang Yi , Izumi Ayaka , Okazaki Erina , Doi Makiko , Hatanaka Yuji , Shimizu Nobutaka , Yoshimura Kazuhiro , Nozawa Masahiro , Yoshikawa Kazuhiro , Uemura Hirotugu 
Published: June 2012

Abstract
As a whole, the concept of thermotherapy is still under study. However, there is an abundant amount basic and pre-clinical published reports that have shown the antitumor effects of hyperthermia in various cancer models. Local, regional and whole body hyperthermia (WBH) has been studied and the effectiveness of the treatment depends largely on the temperature achieved and the duration of treatment. High temperatures, low duration (heat shock) will have a direct killing effect on exposed cells. The limitation to this approach is the restriction of tumor location. Low temperature, high duration WBH is generally considered to be the least toxic but requires long exposures that are generally uncomfortable or inconvenient to the patients. In this study we investigate the therapeutic efficacy of a synthetic far-infrared emitting biomaterial (BR), capable of inducing mild whole body hyperthermia, alone or in combination with chemotherapy against bladder cancer cell lines in vivo.
Immunocompetent and immunodeficient mice were inoculated with a human superficial bladder cancer cell (KU7/GFP) or mouse bladder cancer cell (NBT2), respectively, and treated with BR alone or in combination with doxorubicin (Dox). Mice exposed to BR increased their core body temperature by 1oC (P&lt;0.05) after 2 weeks of exposure. Both immunocompetent and immunodeficient bearing subcutaneous tumor xenografts treated to WBH demonstrated a clear tendency in the reduction of tumor size. Histological analysis showed that tumors exposed to WBH had remarkable granulocyte infiltration accompanied by increased necrosis. Elevated levels of HSP27, HSP70 and HSP90 were detected in tumors of mice exposed to WBH. Increased levels of C-GSF, GM-CSF, TNFα and IL-12p70 corresponded to exposure to WBH. To determine the synergistic effects of WBH and chemotherapy, a survival study was carried out using immunodeficient mice orthotopically inoculated with KU7/GFP cells. Mice treated with Dox or WBH/Dox demonstrated a reduction in tumor size compared to mice treated with WBH and untreated controls. More interestingly, survival rates for control, WBH, Dox and WBH/Dox groups were 50% (5/10), 70% (7/10), 10% (1/10) and 50% (5/10), respectively. No clear differences were noted in HSP expression or granulocyte infiltration in these mice.
Our data suggests that WBH may induce mild antitumor effects; although, the precise mechanism is still unclear, it appears that it may be due to an immuno-stimulatory effect.
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 806. doi:10.1158/1538-7445.AM2011-806
Abstract 855: Flavokawain A inhibits urinary bladder cancer in UPII-mutant Ha-ras transgenic mouse bladder cancer model
Authors: Liu Zhongbo , Li Xuesen , Liu Shuman , Xu Xia , Sun Zheng , Simoneau Anne , Zi Xiaolin 
Published: June 2012

Abstract
Flavokawain A is the predominant chalcone identified from kava extract. We have recently shown that flavokawain A exhibited strong growth inhibitory effects on human bladder cancer cells both in vitro in cell cultures and in vivo in a xenograft mouse model. To examine whether flavokawain A affects specific-stages or course of bladder cancer development, the UPII-mutant Ha-ras transgenic mouse bladder model that mimics human papillary transitional cell carcinoma was used. The homozygous mutant Ha-ras transgenic mice were identified through genotyping using Southern blotting analysis and fed orally with 1g flavokawain A/kg food or 6 g flavokawain A /kg food for 3 or 6 months starting at 6 weeks of age. After treatments, organs are collected and weighted. H&E staining and immunohistochemstry were used to evaluate bladder cancer pathology and expression of biomarkers. All control food- fed male mice died of ureter obstruction and nephrohydrosis within 6 months of treatment, while more than 50% of mice fed with 6g flavokawain A /kg food for 6 months survived beyond the 6 months of treatment. The mean bladder weight in 6g flavokawain /kg food fed male mice also decreased by 66% compared to control treated mice for 3 months. Mouse pathology analysis showed that control mice exhibited poorly differentiated transitional cell carcinoma, while that flavokawain A treated mice presented well differentiated tumors. Compared to the dose of 6g/kg, a 1g/kg dose of flavokawain A is less effective in inhibition of bladder cancer development in this transgenic model. In addition, immunohistochemistry staining of Skp2 revealed that Skp2 oncoprotein expression in urothelium was also significantly decreased in flavorkawain A treatment group compared to control group. Taken together, our results suggest the potential usefulness of flavokawain A in treatment of superficial urinary bladder cancer.
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 855. doi:10.1158/1538-7445.AM2011-855
Abstract 86: DNA methylation of tumor suppressor and metastasis suppressor genes in circulating tumor cells
Authors: Chimonidou Maria , Strati Areti D. , Tzitzira Alexandra , Sotiropoulou Georgia , Malamos Nikos , Georgoulias Vassilis , Lianidou Evi 
Published: June 2012

Abstract
Background: Circulating tumor cells (CTCs) are associated with prognosis in a variety of human cancers and have been proposed as a liquid biopsy for follow up examinations. We show, that established tumor suppressor and metastasis suppressor genes (CST6, BRMS1, and SOX17) are epigenetically silenced in CTCs isolated from peripheral blood of breast cancer patients.
Methods: Peripheral blood was obtained from 56 patients with operable breast cancer, 27 patients with verified metastasis and 23 healthy individuals. Extraction of genomic DNA was performed in the EpCAM positive immunomagnetically selected CTC fraction of peripheral blood mononuclear cells (PBMC). DNA samples were subjected to sodium bisulphite conversion and tested for the presence of methylated and unmethylated gene promoter sequences by methylation specific PCR (MSP). All samples were also checked for CK-19 expression by RT-qPCR.
Results: In CTCs of patients with operable breast cancer, CST6 promoter methylation was observed in 17.9%, BRMS1 promoter methylation in 30.4%, and SOX17 promoter methylation in 53.6%. In CTCs of patients with verified metastasis, CST6 promoter methylation was observed in 37.0%, BRMS1 promoter methylation in 44.4%, and SOX17 promoter methylation in 74.1%.
Conclusions: Our results provide the first evidence that DNA methylation of tumor suppressor and metastasis suppressor genes is a hallmark feature of CTCs and confirm their heterogeneity. Our findings add a new dimension on the malignant nature of CTCs and may underlie the acquisition of malignant properties, including their stemlike phenotype. Moreover, these epigenetic markers open new possibilities for the exploitation of CTCs in monitoring cancer 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 86. doi:10.1158/1538-7445.AM2011-86
Abstract 901: Specificities of CYFRA monoclonal antibodies KS 19.1 and BM 19.21 to cytokeratin 19
Authors: Vasko Ann-Jeanette , Thorne George D. , Kettlety Timothy R. , Li Zhong-Qian 
Published: June 2012

Abstract
CYFRA 21-1 measures cytokeratin fragments of cytokeratin 19 with the aid of two specific monoclonal antibodies (mAb), BM 19.21 and KS 19.1. CYFRA 21-1 has been adopted in several immunoassays as a tumor marker for non-small-cell lung cancer (Sanchez-Carbayo et al. Clin Chem 1999; 45: 1944-1953). We evaluated the binding of these antibodies to cytokeratin 19 and three other types of cytokeratin. Potential cross-reactivity of these antibodies with six cancer biomarker antigens was also evaluated. METHODS: SDS-PAGE and Western blotting were used to observe the binding of KS 19.1 and BM 19.21 with recombinant cytokeratin 8, 14, 18 and 19. An ARCHITECT CYFRA 21-1 assay was used to investigate whether cancer biomarker antigens AFP, beta-HCG, CA 125, CA 15-3, CA 19-9 and CEA interfere with the binding of these two antibodies to cytokeratin 19. 10 – 100 fold of the normal reference levels (8 ng/mL AFP, 5 mIU/mL beta-HCG, 35 U/mL CA 125, 37 U/mL CA 19-9 and 5 ng/mL CEA) of these biomarker antigens were spiked into five (5) serum samples. The concentration of the biomarker antigen CA 15-3 used for this study was 10 and 17 fold of its normal reference levels (31.3 U/mL). RESULTS: SDS-PAGE and Western blotting showed that KS 19.1 and BM 19.21 antibodies bind specifically to cytokeratin 19. KS 19.1 and BM 19.21 antibodies exhibited no binding to cytokeratin 8, 14 and 18 even though the total amount of cytokeratin 19 loaded was less than that of the other three cytokeratin's. Cancer biomarker antigens AFP, beta-HCG, CA 125, CA 15-3, CA 19-9 and CEA did not interfere with the binding of these two antibodies to cytokeratin 19 significantly. Mean cross reactivity of each biomarker was 5% (1% – 11%) for AFP, 4% (0% – 7%) for beta-HCG, 4% (0% – 15%) for CA 125, 6% (0% – 15%) for CA 15-3, 3% (0% – 6%) for CA 19-9 and 2% (0% – 4%) for CEA. CONCLUSIONS: Monoclonal antibodies KS 19.1 and BM 19.21 bound to cytokeratin 19 specifically and showed no cross reactivity with cytokeratin 8, 14 and 18 in Western blotting. Also cytokeratin 19-binding specificity was not significantly interfered significantly by cancer biomarker antigens AFP, beta-HCG, CA 125, CA 15-3, CA 19-9 and CEA in an ARCHITECT CYFRA 21-1 assay.
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 901. doi:10.1158/1538-7445.AM2011-901
Abstract 952: Protein kinase C theta (PKCθ) and c-Jun regulate proliferation through cyclin D1 in KIT-independent gastrointestinal stromal tumors
Authors: Ou Wen-Bin , Fletcher Christopher D.M. , Demetri George D. , Fletcher Jonathan A. 
Published: June 2012

Abstract
Oncogenic KIT or PDGFRA receptor tyrosine kinase (RTK) mutations are compelling therapeutic targets in gastrointestinal stromal tumors (GISTs), and the KIT/PDGFRA kinase inhibitor, imatinib, is standard of care for patients with metastatic GIST. However, most patients eventually develop clinical resistance to imatinib and other KIT/PDGFRA kinase inhibitors due to acquisition of secondary mutations in the KIT kinase domain, genomic amplification of KIT, or activation of alternate oncoproteins. Approximately 10% of KIT-dependent GIST metastases lose KIT expression at time of clinical progression during imatinib therapy. We performed whole transcriptome sequencing in KIT-expressing GIST vs. KIT-negative GIST, and thereby identified strong cyclin D1 expression only in KIT-negative GISTs. KIT-negative GISTs showed complete loss of the GIST biomarker, PKCθ, and restoration of PKCθ expression in these cells resulted in loss of Cyclin D1 expression. Lentivirus-mediated CCND1 (Cyclin D1) short hairpin RNA (shRNA) knockdown resulted in profound anti-proliferative and pro-apoptotic effects in KIT-negative GIST cell lines, and was associated with activation (dephosphorylation) of the tumor suppressor Rb and upregulation of the p27 CDK inhibitor. c-Jun expression levels paralleled the Cyclin D1 expression in the GIST lines, and c-Jun shRNA knockdown resulted in downregulation of cyclin D1 in the KIT-negative GIST lines, and was accompanied by profound anti-proliferative effects, including p27 upregulation, and pro-apoptotic effects as evidenced by PARP cleavage. By contrast, cyclin D1 and c-Jun silencing showed little anti-proliferative and pro-apoptotic effects in KIT-positive, KIT-dependent GIST lines. These findings show that cyclin D1 and c-Jun overexpression serve a crucial oncogenic role in KIT-independent GISTs, including those enabling clinical resistance to imatinib or sunitinib targeted kinase inhibitor therapies. Our findings also show that PKCθ downregulation and c-Jun upregulation coordinately enable cyclin D1 overexpression in KIT-independent GISTs. These novel findings highlight the relevance of c-Jun/cyclin D1 as novel therapeutic targets in GISTs that have lost KIT oncoprotein expression.
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 952. doi:10.1158/1538-7445.AM2011-952
Abstract 972: Epigenetic-microRNA networks in colon cancer stem cells
Authors: Chatziapostolou Maria , Iliopoulos Dimitrios 
Published: June 2012

Abstract
Although chemotherapeutic regimens often suppress tumor growth, cancer patients show high variability in their responses and commonly develop resistance to these drugs and recurrence of the tumor. To explain this phenomenon, the cancer stem cell hypothesis suggests that tumors contain a small number of tumor-forming, self-renewing, cancer stem cells (CSCs) within a population of non-tumor-forming cancer cells. In our study, we have identified that CD133+/CD44+/ALDH1+ colon cancer cells are able to self-renew, form tumors in immunodeficient (rag2-/-gammac-/-) mice and are highly resistant to 5-fluorouracil (5-FU) chemotherapy treatment. Several studies have identified that microRNAs are central regulators of oncogenesis, however their role in CSC formation and maintenance has not been elucidated. In order to identify microRNAs that suppress the growth of CD133+/CD44+/ALDH1+ colon cancer stem HCT-116 cells, we transfected a library of 810 microRNAs in these cells and evaluated their viability 24h post transfection. The microRNA library screen revealed 8 microRNAs that suppressed more than 80% colon CSC growth. Specifically, miR-26b inhibited most effectively (96%) colon CSC growth. In addition, microRNA microarray analysis revealed that miR-26b expression is highly decreased in colon CSCs in comparison to colon non-stem cancer cells (NSCCs), suggesting the importance of miR-26b in colon CSC growth. Bioinformatic and molecular analyses revealed that miR-26b targets directly the 3’UTR of the enhancer of zeste homolog 2 (EZH2). Overexpression of EZH2 in colon NSCCs resulted in formation of colon CSCs, suggesting the importance of EZH2 in colon CSC formation. Furthermore, chromatin-immunoprecipitation-sequencing (ChIP-seq) analysis showed that miR-26b overexpression in colon CSCs reactivates the expression of genes repressed by H3K27 tri-methylation. Interestingly, we have identified that miR-26b promoter area is a direct target of EZH2 suppressed by H3K27 tri-methylation. The transcriptional signature of the miR-26b-EZH2 network was also identified in colon CSCs derived from human colon cancer tumors. In addition, miR-26b targeted selectively colon CSCs and acted together with 5-FU chemotherapy to block tumor growth and prolong remission in colon cancer mouse models. Taken together, these data suggest the identification of novel epigenetic-microRNA network in colon CSCs and provide the rationale and experimental basis for using the combination of miR-26b and chemotherapy drugs to improve treatment of patients with colon cancer.
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 972. doi:10.1158/1538-7445.AM2011-972
Abstract 984: The role of branched-chain amino acids (BCAAs) oxidation in the survival of brain metastatic breast cancer cells
Authors: Wu Xuefeng , Weihua Zhang 
Published: June 2012

Abstract
Background: Glucose is the main source of energy for most cells. When the glucose is limited some cells can use amino acids to support their survival. This ability of oxidizing branched chain amino acids (BCAAs) of the brain metastatic breast cancer cells was investigated.
Methods: Breast cancer cell lines, MDA-MB-231 cell and its brain metastatic derivative MDA-MB-Br3 were used in this study. The survivability, ability of oxidizing BCAAs and expression of BCAA oxidation related enzymes of these cells were determined.
Results: MDA-MB-Br3 cells survived well and oxidized more BCAAs than MDA-MB-231 cells when cultured in glucose free medium. Accordingly, the activity of branched-chain a-ketoacid dehydrogenase complex of MDA-MB-Br3 cells is significantly higher than that of the MDA-MB-231 cells.
Conclusions: The breast cancer cell line MDA-MB-Br3 can use BCAAs as a resource of energy for survival in the environment with very low level of glucose.
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 984. doi:10.1158/1538-7445.AM2011-984
Abstract 991: Regulation of glucose metabolism by HIF in pancreatic cancer
Authors: Singh Pankaj K. , Purohit Vinee , Chaika Nina , Johnson Keith R. , Hollingsworth Michael A. 
Published: June 2012

Abstract
Pancreatic cancer is the fourth leading cause of cancer related deaths with a five-year survival rate of 5.5%. It is characterized by extremely aggressive tumor growth rate and high incidence of metastasis. Like other cancers, pancreatic cancer displays alterations in cellular metabolism, which holds significant promise for better management/cure of the disease. One of the most common and profound biochemical phenotypes of animal and human cancer cells is their ability to metabolize glucose at high rates, even under aerobic conditions. Several oncogenes and tumor suppressors have been implicated in altering tumor cell metabolism in order to facilitate tumor growth and metastasis. The objective of this study was to characterize the role of hypoxia inducible factors (HIF) in glucose metabolism in pancreatic cancer cell lines under normoxic and hypoxic conditions. We screened a panel of pancreatic cancer cell lines for glucose uptake under normoxic and hypoxic conditions. Although the effect of hypoxia on glucose uptake was variable in different pancreatic cancer cell lines, it correlated well with the expression levels of HIF-1alpha and HIF-2alpha. Furthermore, dual knockdown of HIF-1alpha and HIF-2alpha had similar negative effect on growth rate under hypoxic conditions, as did the treatment with glycolysis inhibitor 3-BrPA. These studies suggest that HIF factors regulate growth in pancreatic cancer by regulating glycolysis. Hence, combining strategies to target metabolism along with the strategies to target signal transduction might synergistically aid in diminishing cancer cell growth and invasiveness.
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 991. doi:10.1158/1538-7445.AM2011-991