bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5291: Non-coding satellite RNAs are highly expressed in cancer adjacent lesions of human pancreatic carcinoma and may promote oncogenesis .
Authors: Kishikawa Takahiro 
Published: August 2014

Abstract
It was believed that most satellite repeats in pericentric heterochromatin region were silenced and rarely transcribed into RNAs. However, a few reports suggest that non-coding satellite RNAs may play a significant role in cell division, heterochromatin remodeling or DNA damage such as other well-researched non-coding RNAs. In fact, a next generation digital gene expression method recently revealed that human satellite II (HSATII) transcripts are highly and specifically upregulated in human pancreatic tumors. To further explore these findings, we examined the precise localization of HSATII transcripts in human clinical pancreatic tissues by in situ hybridization using highly sensitive locked nucleic acid-modified oligonucleotide probes. Unexpectedly, HSATII RNAs were not detected in pancreatic ductal cancerous lesions, in almost all cases examined.
Instead, HSATII RNAs were clearly expressed in non-cancerous adjacent acinar cells, surrounding carcinoma tissues. On the other hand, none of normal or inflammatory pancreatic tissues derived from the ones without cancer expressed HSATII RNAs. While,
HSATII transcript expression in normal pancreatic ductal cells could not be induced in vitro even under stress conditions which mimic the tumor-adjacent environments, the cells with ectopic expression of HSATII transcripts showed the increase foci of gH2AX, which may reflect the increased genomic instability. These results suggest that the expression of HSATII may not be phenotypic changes in cancers but may directly contribute to the oncogenesis in the cells in precancerous lesions.
Citation Format: Takahiro Kishikawa. Non-coding satellite RNAs are highly expressed in cancer adjacent lesions of human pancreatic carcinoma and may promote oncogenesis . [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5291. doi:10.1158/1538-7445.AM2013-5291
Abstract 5308: CD9, CD63 and CD82 tetraspanins expression profile in vulvar carcinomas.
Authors: Carvalho Katia C. , Rocha Rafael M. , Cunha Isabela W. , Soares Fernando A. 
Published: August 2014

Abstract
Background: Vulvar carcinomas are approximately 95 % of all vulvar tumors. This cancer presents good prognosis since early diagnosed, and survival depends of inguinal lymphonode commitment, with about 30% of patients presents lymphonode metastasis. The mechanisms involved in biological behavior of vulvar cancer remain unclear and its treatment involves physical mutilation and psychosocial factors of patients. Therefore, identification of features related with this tumors development or genesis can contribute to its knowledge and treatment. The tetraspanins are proteins that are involved in several biological processes including cell proliferation, adhesion, invasion and migration. Their reduction or lack of expression is frequently reported in metastatic and poor prognosis tumors. Our aim was to analyze CD9, CD63 and CD82 tetraspanins expression profile in vulvar carcinoma compared to normal tissue. Methods: All samples were obtained from Pathology Department of Hospital A. C. Camargo, Sao Paulo, Brazil. TMA block was constructed with 150 paraffin-embedded samples and was used in immunohistochemical assay. The tissue sections were incubated with specific antibodies against CD9, CD63 and CD82, following manufacturer's instruction. The slides were evaluated and scored semiquantitatively by assessing the staining intensity in tumor cells and the frequency of positive cells. Results: The Immunohistochemical analysis showed that all tetraspanins were expressed in tumor samples with different intensity and frequency. CD63 were expressed by a higher samples number (90%), with stronger staining both cytoplasm (79%) and nucleus (11%). Lack of CD63 expression was described in metastatic melanomas lesions, while no metastatic lesions shows higher levels of this protein. Seventy five percent of our samples expressed CD9, exclusively on cellular membrane. CD82 showed positive reaction in 45% of the samples with weakly or moderate staining, both nucleus and cytoplasm. The association of the downregulation of CD9 and/or CD82 with a worse prognosis has been shown in breast, cervical, endometrial, esophageal, head and neck, and others carcinomas. Moreover, CD82 is considered to be an important metastasis suppressor. Conclusion: Our preliminary results showed that tetraspanins may have an important role in vulvar carcinomas and CD82/CD63 nuclear expression must be better investigated. Further analyses are ongoing.
Citation Format: Katia C. Carvalho, Rafael M. Rocha, Isabela W. Cunha, Fernando A. Soares. CD9, CD63 and CD82 tetraspanins expression profile in vulvar carcinomas. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5308. doi:10.1158/1538-7445.AM2013-5308
Abstract 5320: miR-211 expression inhibits MMP-9-induced phenotype and tumor growth in lung adenocarcinoma cancer stem cells in vitro and in vivo.
Authors: Chetty Chandramu , Chittivelu Subramanyam , Rao Jasti S. 
Published: August 2014

Abstract
MicroRNAs are small non-coding RNAs that post-transcriptionally modulate gene expression by degrading or repressing the translation of target messenger RNAs (mRNA). MicroRNAs play fundamental roles in diverse biological and pathological processes, including cell proliferation, differentiation, apoptosis, and carcinogenesis. MicroRNAs have been revealed to be involved in various stages of cancer development, showing that abnormal miRNA expression plays a critical role in modulating expression of known oncogenes or tumor suppressor genes during cancer progression. In the present study, we observed that miR-211 expression was significantly lower in human non-small cell lung cancer (NSCLC) than their matched normal tissue samples, and we elucidated the tumor suppressor role of miR-211 using in vitro and in vivo models. We demonstrated that the expression of precursor of miR-211 (p-mir-211) inhibits radiation-induced invasive nature and tumor progression of NSCLC-initiating cells (NSCLC-ICs) in vitro and in vivo. Overexpression of miR-211 in NSCLC-ICs inhibited radiation-induced MMP-9 expression and invasive nature. Overexpression of miR-211 also inhibited epithelial to mesenchymal transition (EMT), which caused a decline in the mesenchymal markers vimentin, beta catenin and TGF-beta signaling molecules while increasing the epithelial marker, E-cadherin. Further, miR-211-treatment inhibited pre-established tumors in orthotopic mouse models. In addition, MMP-9 immunoreactivity decreased in tumor sections from mice that received miR-211 treatment as compared to tumor sections from mice that received control treatments. Finally, the apoptotic population was significantly increased in tumor sections from mice that received miR-211 treatment. Our data suggest miR-211 as a novel approach for the inhibition of radiation-induced invasion and tumor growth in NSCLC-ICs.
Citation Format: Chandramu Chetty, Subramanyam Chittivelu, Jasti S. Rao. miR-211 expression inhibits MMP-9-induced phenotype and tumor growth in lung adenocarcinoma cancer stem cells in vitro and in vivo. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5320. doi:10.1158/1538-7445.AM2013-5320
Abstract 5322: CD44+ prostate cancer cells are regulated by microRNA-708: A novel role of microRNA with potential prognostic and diagnostic significance in prostate cancer .
Authors: Saini Sharanjot , Arora Sumit , Majid Shahana , Shahryari Varahram , Yamamura Soichiro , Chang Inik , Chiyomaru Takeshi , Fukuhara Shinichiro , Deng Guoren , Tanaka Yuichiro , Dahiya Rajvir 
Published: August 2014

Abstract
A challenging aspect of prostate cancer (PCa) is the high rates of recurrence associated with the disease. About 40% of men with localized prostate cancer suffer from relapse after initial therapy. In these cases, androgen ablation therapy is used to reduce tumor burden/circulating PSA to low or undetectable limits. However, most patients suffer from disease recurrence, as monitored by rising PSA and tumor progression to hormone refractory/castration resistant prostate cancer that is essentially untreatable. Tumor recurrence has been attributed to the existence of tumor-initiating cells (TIC) within the bulk of the tumor; CD44 is an important marker for these cells. In this study, we demonstrate that miR-708 is a key negative regulator of CD44+ subpopulation of PCa cells. miR-708 was underexpressed in CD44+ cells from PCa xenografts. Reconstitution of miR-708 in PCa cell lines or CD44+ PCa cells led to decreased tumorigenicity in vitro. Intratumoral delivery of synthetic miR-708 oligonucleotides triggered regression of established tumors in a murine xenograft model of human prostate cancer. Conversely, miR-708 silencing in a purified CD44- population of PCa cells promoted tumor growth. Functional studies validated CD44 to be a direct target of miR-708. Also, we identified Androgen Receptor (AR) and the serine/threonine kinase AKT2, a member of the PI3K/AKT signaling pathway as functional targets of miR-708. Clinically, low miR-708 expression was associated significantly with poor survival outcome, tumor progression and recurrence in prostate cancer patients. In view of these results we propose that reduced miR-708 expression leads to prostate cancer initiation, progression and development by regulating expression of CD44, AR, AKT2, which in turn regulate proliferative, invasive and migratory abilities of prostate cancer cells. Therefore, miR-708 may represent a novel therapeutic target for prostate cancer.
Citation Format: Sharanjot Saini, Sumit Arora, Shahana Majid, Varahram Shahryari, Soichiro Yamamura, Inik Chang, Takeshi Chiyomaru, Shinichiro Fukuhara, Guoren Deng, Yuichiro Tanaka, Rajvir Dahiya. CD44+ prostate cancer cells are regulated by microRNA-708: A novel role of microRNA with potential prognostic and diagnostic significance in prostate cancer . [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5322. doi:10.1158/1538-7445.AM2013-5322
Abstract 5344: IGF1-receptor expression is regulated by miR-100 in metastatic pancreatic cancer cells.
Authors: Huang Justin S. , Egger Michael , Grizzle William E. , McNally Lacey R. 
Published: August 2014

Abstract
Patients with pancreatic adenocarcinoma have the lowest 5-year survival and yearly rates of incidence are almost equivalent to the mortality rates. Long-term cure rates by standard therapies are disappointing due to disseminated disease at diagnosis and chemotherapeutic resistance. New therapeutic targets are necessary for decreasing the progression of pancreatic cancer and identifying targets specific to metastasis would improve patient care. In this study, we evaluated the levels of microRNA of metastatic and non-metastatic cell lines. The expression level of microRNAs and mRNAs were identified through microarray analysis by examining and comparing 5 pancreatic cancer cell lines, two that can metastasize in vivo (S2VP10, S2CP9) versus three that do not metastasize (MiaPaCa2, Panc-1, and ASPC-1). MicroRNA analysis indicated an increase in miR-100 and a decrease in miR-138 expression in metastatic cancer cells. Microarray analysis of differentially expressed mRNAs between metastatic and non-metastatic pancreatic cell lines also indicated increased insulin growth factor-1 receptor (IGF1-R) expression (p&lt;0.0001) in metastatic pancreatic cancer cell lines compared to non-metastatic pancreatic cancer cell lines. To confirm these results from microarray analysis, western blot and immunocytochemistry was performed. Western blot revealed IGF1-R expression was 7 fold increased in metastatic cancer cell lines compared to non-metastastatic cell lines. In addition, downstream expressions of proteins GRB2 and phosphorylated PI3K also were increased in aggressive cancer cell lines. Immunocytochemistry confirmed the linkage of IGF1-R to miR-100 as cells transfected with miR-100 inhibitor showed a decrease in IGF1-R. However, cells transfected with a miR-138 mimic did not affect IGF1-R expression. IGF1-R may be an important molecular feature and a useful biomarker for diagnosis and treatment of metastatic pancreatic cancer.
Citation Format: Justin S. Huang, Michael Egger, William E. Grizzle, Lacey R. McNally. IGF1-receptor expression is regulated by miR-100 in metastatic pancreatic cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5344. doi:10.1158/1538-7445.AM2013-5344
Abstract 5349: Aberrant trimethylation of histone H3 lysine 27 is induced by chronic inflammation in mouse colonic epithelial cells, and is involved in the formation of a field for cancerization.
Authors: Takeshima Hideyuki , Ikegami Daigo , Wakabayashi Mika , Niwa Tohru , Kim Young-Joon , Ushijima Toshikazu 
Published: August 2014

Abstract
A field for cancerization (field defect), where genetic and epigenetic alterations are accumulated in normal-appearing tissues, is involved in human carcinogenesis, especially cancers associated with chronic inflammation. While aberrant DNA methylation is involved in the field defect and induced by chronic inflammation [Ushijima and Hattori, Clin Cancer Res, 2012], it is still unclear for trimethylation of histone H3 lysine 27 (H3K27me3), which is involved in gene repression independent of DNA methylation and functions as a pre-mark for aberrant DNA methylation. In this study, using a mouse colitis model induced by dextran sulfate sodium (DSS), we aimed to clarify whether or not aberrant H3K27me3 is induced by inflammation and involved in a field defect.
Analysis of H3K27me3 levels in colonic epithelial cells by chromatin immunoprecipitation combined with CpG island microarray analysis (ChIP-on-chip analysis) revealed that H3K27me3 levels were increased or decreased for 266 genomic regions by aging, and more extensively (27 increased and 3,782 decreased regions) by colitis. Among the 3,809 regions with alterations by DSS-induced colitis, 212 regions overlapped with those whose alterations were induced by aging. Analysis of the temporal profiles of H3K27me3 levels in the course of DSS treatment revealed that increase or decrease of H3K27me3 was induced as early as two weeks after the initiation of DSS treatment, and persisted at least for 16 weeks, even after the inflammation disappeared. Some of the aberrant H3K27me3 in colonic epithelial cells was carried over into colon tumors. Furthermore, H3K27me3 acquired at Dapk1 by colitis was followed by increased DNA methylation, supporting its function as a pre-mark for aberrant DNA methylation [Takeshima et al., Carcinogenesis, in press]. Regarding mechanisms of aberrant H3K27me3 induction, expression changes of polycomb-related genes including Ezh2, Kdm6a, and Kdm6b, were not involved.
These results demonstrated that aberrant H3K27me3 can be induced by exposure to a specific environment, such as colitis, and suggested that aberrant histone modification, in addition to aberrant DNA methylation, is involved in the formation of a field defect.
Citation Format: Hideyuki Takeshima, Daigo Ikegami, Mika Wakabayashi, Tohru Niwa, Young-Joon Kim, Toshikazu Ushijima. Aberrant trimethylation of histone H3 lysine 27 is induced by chronic inflammation in mouse colonic epithelial cells, and is involved in the formation of a field for cancerization. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5349. doi:10.1158/1538-7445.AM2013-5349
Abstract 5358: BRCA1 is a negative modulator of the PRC2 complex.
Authors: Zeng Xianzhou , Chen Shuai , Wang Lan , Huang Haojie 
Published: August 2014

Abstract
The Polycomb repressive complex 2 (PRC2) is important for maintenance of stem cell pluripotency and suppression of cell differentiation by promoting histone H3 lysine 27 trimethylation (H3K27me3) and transcriptional repression of differentiation regulatory genes. Here we show that the tumor suppressor protein BRCA1 interacts with EZH2 and other components of PRC2 in mouse embryonic stem (ES) and human breast cancer cells. The BRCA1-binding region in EZH2 overlaps with the non-coding RNA (ncRNA)-binding domain, and BRCA1 expression inhibits the binding of EZH2 to the HOTAIR ncRNA. Decreased expression of BRCA1 causes EZH2 re-targeting genome wide and elevates H3K27me3 levels at PRC2 target loci in both mouse ES and human breast cancer cells. BRCA1 deficiency blocks ES cell differentiation and enhances breast cancer migration and invasion in an EZH2-dependent manner. These results reveal that BRCA1 is a key negative modulator of PRC2 and that loss of BRCA1 inhibits ES cell differentiation and enhances cancer aggressive phenotypes via augmented PRC2 function.
Citation Format: Xianzhou Zeng, Shuai Chen, Lan Wang, Haojie Huang. BRCA1 is a negative modulator of the PRC2 complex. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5358. doi:10.1158/1538-7445.AM2013-5358
Abstract 5373: Genome-wide methylation analysis of prostate tissues reveals global methylation patterns of prostate cancer.
Authors: Luo Jian-Hua , Ding Ying , Chen Rui , Michalopoulos George K. , Nelson Joel B. , Tseng George C. , Yu Yan P. 
Published: August 2014

Abstract
Altered genome methylation is a hallmark of human malignancies. To investigate the global methylation profile of prostate cancer, high-throughput analysis of concordant methylation and gene expression events was carried out for 124 human prostate specimens, including prostate cancer (T), normal adjacent to tumor (AT), and organ donor (OD). Methylated DNA in genomic DNA was immunoprecipitated with anti-methylcytidine antibodies, amplified by adaptor-specific priming PCR, and detected by Affymetrix human whole genome SNP 6.0 chips. Pair-wise analyses of methylation-enriched DNA, along with the matched genome copy number analysis of the same samples, were performed to determine the differential DNA methylation profiles of the T, AT and OD samples. A total of 34,413 methylated genome segments were identified. Among these, 11,481 CpG islands were found in the promoter and exon 1 regions of 9,295 genes. Seven-thousand-six-hundred-forty-one genes were found to be methylated frequently across the OD, AT and T samples, while 239 genes were found to be differentially methylated in only T and 785 genes were methylated in both AT and T but not OD. Genes with promoter methylation and concordant suppressed expression were identified by the pair analyses of T/OD, AT/OD, and T/AT. Pathway analysis suggested that many of the methylated genes in T and AT had cell growth and mitogenic functions. Classification analysis of the differentially methylated genes in T or OD produced a specificity of 89.4% and a sensitivity of 85.7%. The T and AT groups, on the other hand, were only slightly separated by the prediction analysis, indicating a strong field effect. A gene methylation prediction model was developed using the methylation status of 20 genes, and was shown to predict prostate cancer relapse with a sensitivity of 80.0% and a specificity of 85.0%. Collectively, these results suggest methylation patterns may be useful predictive markers of prostate cancer clinical outcomes.
Citation Format: Jian-Hua Luo, Ying Ding, Rui Chen, George K. Michalopoulos, Joel B. Nelson, George C. Tseng, Yan P. Yu. Genome-wide methylation analysis of prostate tissues reveals global methylation patterns of prostate cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5373. doi:10.1158/1538-7445.AM2013-5373
Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Abstract 5379: Recurrent inactivation of PARD3, a polarity-related gene, in squamous cell carcinomas of the lung.
Authors: Bonastre Ester , Zondervan Ilse , Facchinetti Federica , Condom Enric , Savola Suvi , Carretero Julian , Sidransky David , Roz Luca , Brambilla Elisabeth , Sanchez-Cespedes Montse 
Published: August 2014

Abstract
In spite of the recent advances in cancer genomics, the genetics underlying the development of lung squamous cell carcinomas (SCC) is still poorly understood. Here, we investigated the contribution of the cell polarity-related gene, PARD3, to lung SCC carcinogenesis. First, we tested for PARD3 alterations in lung cancer cell lines from various histopathological types. The analysis confirmed an intragenic deletion at the H157 cells and unveiled biallelic mutations in another cell line. Both cell lines are SCCs, which circumscribed PARD3 alterations to this lung cancer type. Next, we extended the genetic screening, which included the determination of mutations and of intragenic deletions by multiplex ligation-dependent probe amplification (MLPA) assay, to lung primary SCCs. Overall, our analysis found that eight per cent of the 125 lung SCCs tested, endured biallelic and tumor-specific alterations at PARD3. The absence of PAR3 protein was evident in those tumors carrying frameshift-type mutations or intragenic deletions, while abnormally high immunostaining of PAR3 was observed in some PARD3 wild type tumors, suggesting positive feedback mechanisms. Further, we demonstrate that, as compared to the wild type, PAR3 mutant proteins were not able to significantly reduce cell growth, restore the appropriate formation of tight junctions or regulate downstream targets, evidencing the lack of function of these mutations. In conclusion, here we report, for the first time, the presence of recurrent and deleterious mutations at PARD3 in lung primary SCCs, which attest to its relevance in the development of lung SSCs.
Citation Format: Ester Bonastre, Ilse Zondervan, Federica Facchinetti, Enric Condom, Suvi Savola, Julian Carretero, David Sidransky, Luca Roz, Elisabeth Brambilla, Montse Sanchez-Cespedes. Recurrent inactivation of PARD3, a polarity-related gene, in squamous cell carcinomas of the lung. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5379. doi:10.1158/1538-7445.AM2013-5379