bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2111: Expression pattern and mechanism of tumor suppression of Rab25
Authors: Cheng Jiming , Ayyagari Vijayalakshmi , Sunkara Bharat , Koirala Sajan , Brahmamdam Abhinav , Rao Krishna A. 
Published: July 2012

Abstract
Introduction: Our previous work has shown that the loss of Rab25 occurs in estrogen receptor (ER) and progesterone receptor (PR) negative breast cancer cell lines and human tumor samples and seems to correlate with an active ras pathway. We have examined the expression levels of rab25 in breast tissue and have investigated the mechanism by which Rab25 exerts its anti-tumorigenic effect. Loss of Rab25 cooperates with mutant Ras to promote tumorigenesis. HIF-1α levels are reduced in Rab25 expressing cells. We have assessed Rab25 binding to the HIF-1α promoter and localized Rab25 to the nucleus, suggesting a novel mechanism for Rab25's antitumor activity and a novel function for Rab25.
Materials and Methods: Cell culture – Normal mammary tissue and the RAO-3 cell line was grown in DFCI-1 medium. Cells were transduced with retroviral supernatant and selected. Expression of Rab25 in transduced cells was determined by RT-PCR and western blot. qPCR analysis- Expression of HIF-1α and Rab25 were quantified using real-time PCR with fluorescence detection. Luciferase report assay – We obtained the HIF-1α promoter fragment and inserted the promoter sequence in the pGL4 luciferase vector and the Luciferase Assay was then performed. Western blot- Protein extracts from both cytosolic and nuclear fraction were tested for Rab25 expression. Immunofluorescence- Frozen mammary tissue slides were stained with luminal and basal markers as well as antibody for Rab25 to confirm localization of Rab25 in both luminal and basal mammary epithelium.
Results:
1. High level expression of Rab25 was found in luminal epithelium in normal human breast tissue. Basal epithelium also expressed Rab25.
2. Tumorigenic mammary epithelial cell lines, RAO-3 and RAO-4, have lost Rab 25 expression with nearly 1/10,000 the level of Rab25 of normal mammary basal epithelium.
3. Rab25 localizes to the nucleus and reduces luciferase activity from the HIF-1α promoter.
4. Expression of Rab25 substantially reduces HIF-1α levels.
Conclusions:
1. Rab25 is a complex molecule that has been described as an intracellular transport protein.
2. It is also a tumor modulator. It can regulate tumor growth and angiogenesis.
3. Rab25 expression can be detected in both luminal epithelium and basal epithelium.
4. Our data indicate novel functions for Rab25 including reduction in HIF-1α expression and localization to the nucleus.
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 2111. doi:10.1158/1538-7445.AM2011-2111
Abstract 2119: Role of annexin A6 in anchorage-independent growth of invasive breast cancer cells
Authors: Sakwe Amos M. , Koumangoye Rainelli , Ochieng Josiah 
Published: July 2012

Abstract
Annexin A6 (AnxA6) is a member of the annexin family of Ca2+-dependent membrane binding proteins that is frequently detected in cell-derived exosomes and on the surface of some cell types. Although its extracellular functions remain unclear, AnxA6 may play important roles in cell-cell and/or cell-extracellular matrix (ECM) interactions via its interactions with chondroitin sulfate containing proteoglycans, the serum glycoprotein fetuin-A and other undefined extracellular matrix components. In support of this notion, recent studies have shown that depletion of AnxA6 in MDA-MB-436 breast cancer cells promoted anchorage-independent cell growth. Here we show that depletion of AnxA6 in BT-549 breast carcinoma cells not only led to impaired cell-cell cohesion and cell spreading onto collagen type IV but also inhibited cell motility and invasiveness. In 3D cultures in growth factor-reduced matrigel, AnxA6-depleted BT-549 cells formed spheroid colonies as opposed to stellate colonies formed by the parental BT-549 cells. We also show that N-cadherin is up-regulated in the motility-impaired AnxA6-depleted cells, suggesting that loss of AnxA6 may uncouple cadherin-based cell-cell interactions as part of the mechanism that determines anchorage-independent cell growth and therefore tumor growth in vivo. Our data also show that the loss of contact inhibition and invasive properties in AnxA6-depleted cells may be partly due to the formation of fewer, elongated and dispersed vinculin-based focal contacts. To verify that these focal contacts may be functionally defective, we show that whereas the MAP kinase (ERK1/2) pathway remained constitutively active, Ca2+-dependent activation of focal adhesion kinase and the phosphoinositide-3 kinase/Akt pathway were strongly inhibited in the AnxA6-depleted BT-549 cells. These data suggest that loss of AnxA6 may promote breast cancer progression via anchorage-independent cell growth due to disruption of functional focal contacts that maintain cell-cell and/or cell-ECM interactions. Supported by grants: 1 SC1 CA134018-01 and DOD W81XWH-07-1-0254
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 2119. doi:10.1158/1538-7445.AM2011-2119
Abstract 2123: Cytoplasmic STAT1 expression level opposes disease-specific survival of sarcoma patients
Authors: Zimmerman Mary A. , Liu Kebin , Lev Dina C. 
Published: July 2012

Abstract
Signal Transducer and Activator of Transcription 1 (STAT1) is a key mediator in the interferon gamma (IFN-γ) signaling pathway. It is well known that IFN-γ-activated STAT1 (pSTAT1) plays a critical role in the suppression of tumor development. However, STAT1 has also been shown to act as a tumor promoter in certain types of cancers. These findings indicate that STAT1 harbors dual functionality, functioning as either a tumor suppressor, or a promoter, a distinction that may ultimately depend on the tumor microenvironment. In this study, we hypothesized that the distribution of STAT1 (cytoplasmic vs nuclear) could affect disease-specific survival of sarcoma patients. STAT1 protein expression levels were examined in 123 soft tissue sarcoma samples from human patients by immunohistochemical staining. We observed a positive correlation between the nuclear STAT1 (pSTAT1) protein level and disease-specific survival. A statistically significant inverse correlation was also observed between the cytoplasmic STAT1 protein level and disease-specific survival in sarcoma patients. We have shown that STAT1 is negatively regulated by an interferon-stimulated gene, Interferon Regulatory Factor 8 (IRF8). Disruption of IRF8 function by ectopic expression of an IRF8 dominant negative mutant resulted in dramatic up-regulation of STAT1, down-regulation of Janus kinase 1 (JAK1) and pSTAT1, and increased metastatic potential of sarcoma cells in an experimental metastasis mouse model. In addition, using microRNA microarray analysis we have identified a possible mechanism for these changes through mi106b. The possibility of cytoplasmic STAT1 and nuclear STAT1 accumulation being responsible for the observed difference in disease-specific survival of sarcoma patients merits further study of the role STAT1's localization plays in cancer progression. Direct evidence of cytoplasmic STAT1 increasing tumor cell survival, as well as confirmation of our proposed mechanism for STAT1 regulation through IRF8 is still needed. Taken together, our research suggests that IRF8 is a negative regulator of cytoplasmic STAT1 and STAT1 is indeed a tumor promoter.
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 2123. doi:10.1158/1538-7445.AM2011-2123
Abstract 2126: Androgen receptor regulates lung cancer progress through modulation of OCT-4 expression
Authors: Lu Hsuan-Hsuan , Yeh Shauh-Der , Chou Yu-Ting , Tsai Yu-Ting , Chang Chawnshang , Wu Cheng-Wen 
Published: July 2012

Abstract
Lung cancer is the leading cause of cancer mortality worldwide with unclear pathogenesis. The annual age-adjusted cancer incidence rates of lung cancer in male is higher than female in the U.S. But the role of androgen/AR in lung cancer has not been demonstrated. Immunohistochemical stain and RT Q-PCR studies demonstrated the overexpression pattern of AR in patients with non-small cell lung cancer (NSCLC) especially in male. Then we focused on the role of AR in lung cancer progression. Knockdown AR by lentivirus infection in NSCLC cell lines significantly suppressed cell proliferation and anchorage-independent growth in soft agar assay through the down-regulation of cyclin D1 expression. Besides, knockdown AR could also suppress the migration and invasion ability in CL1-5 and H1299 cells. In immunodeficient mice, AR-knockdown NSCLC cells showed dramatically decreased tumorigenesis and metastasis ability compared with control cells. Interestingly, we also found that the down-regulation of OCT-4 protein expression in AR knockdown CL1-5 and H1299 lung cancer cells. In conclusion, our data suggest that AR may play important roles in tumor growth and metastasis through its interaction with stemness pathway and it also implies AR pathway may become one of novel therapeutic targets in NSCLC patients.
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 2126. doi:10.1158/1538-7445.AM2011-2126
Abstract 2134: Cyclosporin-A enhances cisplatin induced-apoptosis through inhibition PPIase activity of cyclophinlin A and Akt signaling pathway in a human tongue squamous cell carcinoma
Authors: Zhang Wenfeng , Huang Congfa , Zou Haixiao 
Published: July 2012

Abstract
Purpose: Chemoresistance is a serious problem in squamous cell carcinoma of the tongue, but the mechanism of resistance and strategies against the resistance have not been elucidated. Cyclosporin-A (CsA), an immunosuppressive drug that targets calcineurin and cyclophilin A (CypA), rencent studies show that it enhances apoptosis of chemotherapeutic drugs in various kinds of tumors. The aim of our study was to investigate whether CsA could enhance cisplatin induced apoptosis in tongue carcinoma.
Methods: In the present study, we examined the effect of cisplatin and CsA, individually or in combination in a human tongue squamous cell carcinoma cell line. Tumor cell growth, cell cycle, cell apoptosis, PPIase activity of cyclophinlin A and Akt phosphorylation were examined.
Results: A combination of cisplatin with CsA synergistically attenuates cell gowth viability and markedly increased cleavage of caspase-3 and cytoplasmic histone associated DNA fragments in tongue squamous cell carcinoma cells, compared with single-agent treatment alone. Moreover, anti-apoptotic proteins p53 and Bax/Bcl-2 ratio were significantly increased in the combination therapy group. In contrast, the PPIase activity of cyclophinlin A and Akt phosphorylation were evidently decreased by the combination effect.
Conclusion: Together, our data suggest that CypA and Akt signaling pathway play a key role in cisplatin resistance of the tongue carcinoma cells. The combination therapy with cisplatin and CSA can overcome the chemoresistance of cisplatin, this may be a potentially useful therapeutic option for the human tongue squamous cell carcinoma.
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 2134. doi:10.1158/1538-7445.AM2011-2134
Abstract 3909: Genomic and transcriptomic analysis suggest that primary pleomorphic sarcomas and leiomyosarcomas are two genetically distinct diseases
Authors: Rogatto Silvia R. , Silveira Sara M. , Villacis Rolando A R , Carvalho André L. , Soares Fernando A. , Cunha Isabella W. 
Published: July 2012

Abstract
Malignant fibrous histiocytoma was the most frequent pleomorphic soft tissue sarcoma (STS) histotype, until laborious investigation showed a differentiation in two thirds of the cases, thereby reclassifying many of the tumors into pleomorphic liposarcomas (LPS) and leiomyosarcomas (LMS). Pleomorphic soft tissue sarcoma without any histologically identifiable line of differentiation is designated as undifferentiated pleomorphic sarcoma (UPS). Gene expression studies in UPS initially suggested that the majority of tumors cluster with LMS and LPS but subsequent studies have identified distinct genomic and expression profiles in liposarcomas. In the present study, it was evaluated genomic and transcriptomic alterations in UPS and LMS samples (35 frozen samples) obtained previously to chemo and or radiotherapy and without metastasis at diagnosis. These primary tumors were extensively characterized by immunohistochemistry. Array CGH and large-scale gene expression analysis were evaluated using the Human 44K Agilent oligoarrays according to manufacturer's instructions. Array CGH data were extracted and flagged with Feature Extraction software (version 10.1.1.1), processed using Genomic Workbench Standard (version.5.0.14), with the statistical algorithm ADM-2 and sensitivity threshold of 6.0. DNA copy number alterations were compared with Database of Genomic Variants (DGV; http://projects.tcag.ca/variation/) and with a reference dataset obtained from 83 healthy Brazilian individuals. Genomic gains were more frequently observed in UPS whereas losses were commonly detected in LMS. Some genomic alterations were frequently observed in both groups. Gains at 7q21.13 and losses at 13q14.3 were the most frequent genomic imbalances verified in UPS and LMS, respectively. Gene expression data were extracted using the Feature Extraction software (v. 10.1.1.1) and analyzed by the R software (v. 2.9.2) e TMEV (v. 4.4.1). An unsupervised and supervised analysis was done using the Significance Analysis for Microarray software (SAM) (FDR 0% and 1000 permutations) and Pearson correlation. It was detected three clusters with 101 genes differentially expressed. One cluster was composed 10 UPS, the second with 13 LMS and the last one with both tumors. All genes that differentiated the groups are involved in pathways related to cancer. The identification of specific genomic and transcriptomic imbalances suggests that UPS and LMS might represent genetically distinct diseases and indicate putative molecular diagnostic markers by integrated data analysis.Financial support FAPESP and CNPq.
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 3909. doi:10.1158/1538-7445.AM2011-3909
Abstract 3911: Functional copy number alterations (CNAS) in oral cancer
Authors: Morris Luc G. , Ganly Ian , Taylor Barry , Singh Bhuvanesh , Viale Agnes , Heguy Adriana , Chan Timothy A. 
Published: July 2012

Abstract
Background: Alterations in DNA copy number can functionally affect genes and produce a transformed cancer phenotype. Discoevery of novel cancer genes can be facilitated by identifying genomic regions undergoing frequent, significant alteration. Array comparative genomic hybridization techniques have generated vast amounts of raw copy number data requiring computational analysis to identify aberrations likely to be functional. In this analysis, we present data from a comprehensive computational approach designed to robustly map chromosomal aberrations in oral cavity squamous cell carcinoma (OCSCC).
Methods: DNA was extracted from 31 microdissected OCSCC frozen tumors and hybridized with reference DNA on the Agilent 1M copy number array, containing nearly 1 million probes across the genome at high resolution. The RAE computational framework was used to identify CNAs. In this analysis, segmentation of probe data is first performed using paired reference HapMap data and individual-tumor thresholds to account for stromal admixture and tumor heterogeneity. Scores (single-copy gain, amplification, hemizygous loss, homozygous deletion) are then assigned, followed by soft discrimination thresholding and significance testing with false discovery rate correction. Regions of interest (ROIs) are then agnostically identified as regions of significant (FDR&lt;0.01) alteration, expanded to adjacent loci to account for spatial and amplitude uncertainty. Finally, described copy number polymorphisms were excluded.
Results: 49 ROIs were identified, 27 amplification regions (chromosomes 3,4,5,7,8,9,11,16,18,20,21) and 22 deletion regions (chromosomes 2,3,4,5,7,8,9,10,13,15,16,18,19). ROIs ranged in prevalence from 6.5-77.4% of samples, and encompassed 0-483 genes (total=2799, median=4), and 0-13 microRNAs (total=77, median=0). Eleven ROIs were focal intragenic CNAs. Four ROIs contained no named genes or microRNAs. Hierarchical clustering identified 3 clusters, based on escalating levels of CNA. Complete gene details of the 49 ROIs will be presented.
Conclusions: We report significant regions of CNA in oral cancer, by applying a robust computational framework to identify recurrent chromosomal aberrations in OCSCC, which represent highly significant candidate functional events.
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 3911. doi:10.1158/1538-7445.AM2011-3911
Abstract 3921: Fen-1 inhibition: Synthetic lethal opportunities in Rad54B-defective tumours, ALT-pathway backgrounds and beyond
Authors: Johnson Laura , Hudson Kevin , Lau Alan , O'Connor Mark , Thommes Pia , Durant Steve T. 
Published: July 2012

Abstract
Flap endonuclease-1 (FEN-1) is a 5′-3’ exonuclease and a 5’ flap endonuclease, required for Okazaki fragment processing as well as for long-patch base-excision repair (BER) and non-homologous end-joining (NHEJ). From datamining AstraZeneca's extensive GeAZR database, as well as from Oncomine searches, FEN-1 is over-expressed in lung, ovary, bladder, gastric and 5-FU-resistant cancer cell lines. Screens carried out in yeast (Saccharomyces Genome Database) reveal over 250 genes as being synthetic lethal with the yeast homolog Rad27. Recently using human model systems, FEN-1 suppression was confirmed to be synthetic lethal with the human homolog of yeast Rad54B in Rad54B-deficient colorectal cancer (CRC) cell lines. FEN-1 suppression has also been reported to selectively sensitise hTERT-deficient ALT (Alternative pathway for lengthening telomeres) cell lines. To gain in-house confidence in this synthetic lethal target validation approach, we have used molecular tools to test synthetic lethal opportunities in matched Rad54B-RNAi-suppressed cell lines and confirm selective sensitisation. We also intend to explore further synthetic lethal backgrounds as well as in combination with chemotherapeutic standards of care.
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 3921. doi:10.1158/1538-7445.AM2011-3921
Abstract 3922: TFEB translocation renal carcinoma: Two cases of novel isoforms with unique clinicopathological features
Authors: Inamura Kentaro , Togashi Yuki , Fujiwara Mutsunori , Yamamoto Shinya , Yonese Junji , Fukui Iwao , Ishikawa Yuichi 
Published: July 2012

Abstract
Renal cell carcinoma (RCC) with t(6;11) translocation, involving the transcription factor EB (TFEB), is an extremely rare neoplasm with only 20 cases reported to date. According to the available clinical histories, TFEB translocation renal carcinoma (TFEB RC) is predominantly seen in children and young adults and generally indolent. So far, only two TFEB RC cases have been reported to result in metastases and patient death. We herein present two cases of novel isoforms of TFEB RC with unique clinicopathological features, involving a 37-year-old man and a 47-year-old man. Whereas the former case had an aggressive course, the latter case had the borderline features between TFEB RC and chromophobe type RCC histologically and immunohistochemically except for the nuclear staining of TFEB. Genetically, the former case had two variants of mRNA in RT-PCR analysis, one of which directly connected to the exon 3 of TFEB in sequencing analysis. The latter case had the fusion point of TFEB downstream of the wild-type ATG in exon 3, although the nuclear staining of TFEB was detected. Our data including the molecular characterization contribute to clarify this tumor entity genetically and clinicopathologically. Further investigations with additional new cases are required.
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 3922. doi:10.1158/1538-7445.AM2011-3922
Abstract 4072: Insulin and NADPH-generating enzymes as molecular targets to repress colon cancer cell proliferation
Authors: Al-Dwairi Ahmed , Brown Adam R. , Simmen Rosalia CM , Simmen Frank A. 
Published: July 2012

Abstract
An increasing body of evidence implicates obesity and the attendant hyperinsulinemia as major risk factors for human colorectal cancers. The lipogenic pathway supports growth and survival of colon cancer cells. In particular, inhibition of Fatty Acid Synthase (FASN) or Acetyl-CoA Carboxylase α (ACCα) induces apoptosis of colon cancer cells. The relative involvement in colon cancer initiation, progression and pathogenesis of cytosolic NADPH that is used in lipogenesis remains less clear. In the present study, we have determined the effects of insulin and the involvement of the major NADPH-generating cytosolic enzymes on proliferation of human colon cancer cell lines. Insulin (1-10 nM; to mimic normo- to hyper-insulinemic states) induced a significant increase (7-15%, p &lt; 0.05) in proliferation of HT-29 and HCT-116 colon cancer cell lines in vitro (assayed by MTT assay). Addition of insulin augmented (by 5-10%) proliferation of both cell lines upon concurrent treatment with cancer chemotherapeutic agents (5-fluorouracil, oxaliplatin, irinotecan; each added at a dose &lt; EC50). The insulin-mediated increase in HT-29 cell growth was associated with a 2-3 fold elevation in FASN gene expression and a 50% decrease in expression of the FASN-targeting micro RNAs, miR-103 and miR-107. However, insulin did not induce mRNA abundance for the cytoplasmic NADPH-generating enzymes [Malic Enzyme 1 (ME1), Glucose 6-Phosphate Dehydrogenase (G6PD), 6-Phosphogluconate Dehydrogenase (6PGD), or Isocitrate Dehydrogenase-1 (IDH1]. siRNA-mediated knockdown of FASN or of the individual major cytosolic NADPH-generating enzymes caused decreases in proliferation of HT-29 and HCT-116 cells (15-30%, p &lt; 0.05) compared to the control scrambled siRNA. Data highlight pro-proliferative roles for insulin, FASN and cytosolic NADPH-generating enzymes in colorectal cancer cell growth. Implementation of pharmacologic and/or nutritional means to reduce serum insulin levels, enhance FASN miR expression and inhibit tumor cell NADPH-generation may serve as useful adjuncts for future cancer treatment and prevention. Supported by NIH grant RO1 CA136493 and the Arkansas Biosciences Institute.
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 4072. doi:10.1158/1538-7445.AM2011-4072