bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3943: Affymetrix whole genome microarray analysis of 51 human tumor cell lines representative of 16 different tissues of origin: Unsupervised hierarchical clustering
Authors: Roberts Michael J. , Koratich Michael S. , May Richard D. , Waud William R. , Stackhouse Murray , Penman Andrew D. , Plaxco Meredith S. , Gamble Tommie A. , Berry Kristy L. , Rooney Robert J. , Maxuitenko Yulia Y. 
Published: August 2014

Abstract
The total mRNA for each sample of 51 human tumor cell lines representative of 16 different tissues of origin was split into 3 replicates, and analyzed against the entire human genome using standard Affx WT procedures. Approximately 50% of the samples (25 out of the 51 cell lines tested) exhibited low-level clustering related to their tissue of origin. The remaining 50% (26 out of the 51 cell lines tested) did not cluster with other samples of the same tissue of origin. These data reveal the importance of testing potential anticancer agents in multiple models representative of several different tumors of origin, as there is a 50% chance that the model chosen is not actually representative of the intended tissue of origin. This analysis also showed that the pancreatic cancer cell line CFPAC-1 did not cluster with any other cell line tested, revealing the unique genetic profile of this cell line. Interestingly, the reported lung cancer cell lines NCI-H69 and NCI-H82 clustered more closely with leukemic lines than with lung or any other solid tumor. This is particularly interesting as these lines are known to grow/behave more like a suspension culture than a monolayer. The NCI recently published its genetic analysis of their 60-panel, and they revealed that the MDA-MB-435 cell line, traditionally thought to be a breast cancer cell line, more closely resembled a melanoma line; hence, it was re-classified as a melanoma (likely a metastasized melanoma that was taken from the breast site). Our analysis reveals that another traditional breast cancer cell line, UISO-BCA-1, also clusters more closely with the melanomas (including the MDA-MB-435 cell line), suggesting that this cell line also may have been misclassified. Based on these data, we suggest that any potential anticancer agent showing activity in a particular cell line should be tested in other cell lines that cluster with the active line, and not merely in other lines supposedly representative of the same tissue of origin. Furthermore, in early stage testing, it would be more prudent to test several cell lines from different clusters, rather than several cell lines from different tissues of origin. It follows that by testing orphan drugs against several cell lines from each cluster, it would be possible to significantly narrow (and possibly identify), the likely drug target.
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 3943. doi:10.1158/1538-7445.AM2011-3943
Abstract 3944: PTEN is not directly regulated by miRNA-21 in non-small cell lung cancer
Authors: Sourvinou Ioanna S. , Markou Athina , Kaklamanis Loukas , Tsaroucha Emily G. , Lianidou Evi S. 
Published: August 2014

Abstract
Introduction: PTEN is a well known tumor suppressor gene that plays a crucial role in the regulation of many normal biological processes. Among the mechanisms taking part in its regulation has been demonstrated being miR-21 action, as it has been reported that PTEN consists one of miR-21 target genes. In this study, we speculated on the effect of miR-21 expression levels in non small cell lung cancer tissues towards: a) PTEN mRNA expression levels and b) PTEN protein levels.
Materials and Methods: Thirty pairs of NSCLC fresh-frozen tissues and their corresponding noncancerous tissues were analyzed for the expression of mature miR-21 as well as for the expression of PTEN transcript using RT-qPCR. PBGD was used as a reference gene and for the evaluation of RNA quality in our samples. In parallel, PTEN protein levels were evaluated by immunohistochemistry in the same samples. Deparaffinized sections cut from paraffin-embedded tissue samples were stained with a specific anti-PTEN antibody. Tumor types and stages were determined according to the WHO classification. All samples were analyzed histologically to access the amount of tumor component (at least 70% of tumor cells) and the quality of material.
Results: In 26/30 NSCLC tissues studied (86.7%), PTEN mRNA expression was decreased when compared to adjacent noncancerous tissues, while overexpression of PTEN transcript was perceived in only 4 samples (13.3%). Evaluation of PTEN protein level in these specimens revealed that in 28/30 samples (93.3%), PTEN protein was detected, while in only 2/30 samples (6.7%) PTEN protein loss was observed. The respective data for miR-21 expression levels indicated that PTEN mRNA as well as protein levels were independent of miR-21 expression status in non small cell lung cancer samples.
Conclusion: Our data indicate for the first time that in NSCLC miR-21 expression levels do not directly regulate PTEN protein levels. PTEN protein was detected by IHC in the vast majority of NSCLC tissues despite the fact that PTEN mRNA expression levels were lower in cancerous tissues than in the corresponding noncancerous tissues.
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 3944. doi:10.1158/1538-7445.AM2011-3944
Abstract 3947: MicroRNA-127 (miR127) promotes cell migration and invasion in lung adenocarcinoma cells
Authors: Ho Chiu-Yi , Lee Tai-Lin , Hsu Hui-Chen , Chen Jeremy Jian-Wei , Tsai Meng-Feng 
Published: August 2014

Abstract
MicroRNAs (miRNAs) are small non-coding RNAs, approximately 20-23 nucleotides in length. The specific functions of miRNAs involved in several cellular processes, including metabolism, development, differentiation, proliferation, apoptosis and tumorigenesis. In order to identify the invasion/metastasis related miRNA in lung cancer, the cell line model (lowly invasive lung cancer cells, CL1-0, and highly invasive lung cancer cells, CL1-5) and human miRNA microarray were carried out. In this study, we selected one of the invasion/metastasis related miRNAs, miR-127, derived from our microarray results for further functional characterization. Recently reports have indicated that human miR-127 was highly expressed in normal prostate and bladder tissues but was remarkably down-regulated in the corresponding tumors. miR-127 may function as a tumor suppressor in human bladder and prostate cancer cells. However, the role of the miR-127 in lung cancer cell proliferation, migration and invasion ability still remains unclear. The miR-127 expression level in various invasive capability lung cancer cell lines were also verified using stem-loop real time RT-PCR. We have constructed and established a miR-127 constitutive expression system in CL1-0 lung cancer cells using pSilencer3.1 vector, and we also knockdown the miR-127 expression in CL1-5 and A549 lung cancer cells using anti-miR127 modified oligonucleotide. Our results shown that over-expression of miR-127 can increase lung cancer cell proliferation, migration, and invasion ability. Finally, we suggest that miR-127 may be acting like an oncogene in lung adenocarcinoma cells. These results will provide important information and help us to understand the roles of miR127 in lung 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 3947. doi:10.1158/1538-7445.AM2011-3947
Abstract 3949: Micro-RNA regulated EGFR expression in head and neck squamous cell carcinoma
Authors: Hauser Belinda R. , Califano Joseph , Gu Xinbin , Hao Yubin 
Published: August 2014

Abstract
Purpose: Each year in the United States there are more than 65,000 Americans diagnosed with head and neck cancer and 25,000 die from this disease. Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous disease with complex molecular abnormalities, including overexpression of epidermal growth factor receptor (EGFR). The overexpression of EGFR is seen in 80-90% of HNSCC cases and has been shown to be an indicator of poor prognosis and survival in oral cancer patients. The molecular mechanism of EGFR gene expression is poorly understood in HNSCC. MicroRNAs are a new class of posttranslational regulators of gene expression and are a useful target in understanding EGFR gene expression in HNSCC. We hypothesize that microRNAs may play an important role in EGFR gene overexpression during HNSCC processes. Design Methods: We generated stably expressing exogenous miRNA-7 or miRNA-128 in cell lines (JHU-06,-011,-013,-019, -022, and -029 using lentivirus infection, performed colony formation assays to determine cell growth and proliferation, QRT-PCR to analyze gene expression, and Western blot analysis to evaluate protein expression. Results: We found that the miR-7 and -128 transfection efficiency were quite different in these six cell lines. The transfected cell lines stably expressed exogenous miR-7 or -128. Compared with the control cells, the levels of EGFR protein and cell viability were significantly lower in miR-7, -128 transfected HNSCC cell lines. CONCLUSION: We successfully constructed the stably expressing exogenous miR-7, -128 HNSCC cell lines and validated that miR-7,-128 can down-regulate EGFR expression by specifically targeting the EGFR mRNA 3’UTR. MiR-7 and miR-128 have potential to serve as a therapeutic approach to specifically target EGFR in HNSCC. This work was supported in part by grants P20 CA118770 from National Cancer 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 3949. doi:10.1158/1538-7445.AM2011-3949
Abstract 395: Chemokine ligand 7 expression in liver metastasis of colorectal cancer
Authors: Cho Yong Beom , Hong Hye Kyung , Shin Hee Jung , Choi Hee-Jung , Kim Seok-Hyung , Choi Yoon-La , Choi So-Jung , Kim Jhingook , Kim Hee Cheol , Yun Seong Hyeon , Lee Woo Yong , Chun Ho-Kyung 
Published: August 2014

Abstract
The main cause of death for colorectal cancer (CRC) patients is the development of metastatic lesions at sites distant from the primary tumor. Therefore, it is important to find biomarkers that are related to the metastasis and to study the possible mechanism. Recent data have shown that soluble attractant molecules called chemokines support the metastasis of certain cancers to certain organs. To identify molecular regulators that are differentially expressed in liver metastasis of CRC, PCR array was performed and CCL7 showed remarkable overexpression in liver metastatic tumor tissues. To validate the result of PCR array, 30 patients with primary CRC and liver metastases were selected. Immunohistochemistry and real-time PCR analysis showed that CCL7 was expressed in normal colonic epithelium and the expression was higher in liver metastases than in primary CRC. CCR1, CCR2, and CCR3, receptors of CCL7, were not expressed in normal colonic epithelium nor colon and metastatic cancer, but expressed in normal hepatocytes and stroma by immunohistochemical staining. Real-time PCR showed that the expressions of CCR1, CCR2, and CCR3 were also higher in liver metastases than in primary CRC. There would be chemokine/chemokine receptors interactions between CCL7 and its receptors in liver, which supply the environment for metastatic colon cancer cells to survive and proliferate in liver.
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 395. doi:10.1158/1538-7445.AM2011-395
Abstract 3954: Identification of microRNAs epigenetically silenced in bladder cancer
Authors: Shimizu Takashi , Suzuki Hiromu , Kitamura Hiroshi , Yamamoto Eiichiro , Imai Kohzoh , Tsukamoto Taiji , Toyota Minoru 
Published: August 2014

Abstract
Purpose: Bladder cancer is the one of the most common malignancies in the urothelial tract. MicroRNAs (miRNAs) are small, non-coding RNAs that control gene expression post-transcriptionally, either by degradation of target mRNAs or by inhibition of protein translation. MiRNAs are involved in cancer development and progression, acting as tumor suppressors or oncogenes. Recent studies have demonstrated a role of DNA methylation in silencing miRNAs in bladder cancer. The aim of current study is to identify bladder cancer-related miRNAs by screening epigenetically silenced miRNAs in bladder cancer.
Materials & Methods: Two bladder cancer cell lines (T-24, UM-UC3) were treated with or without 5-aza-2’deoxycytidine (5-aza-dC) and 4-phenylbutyric acid (4-PBA), and expression of mature miRNAs was examined using a TaqMan Low Density Array System. We used UCSC genome browser to examine if CpG islands are located in the proximal upstream of the miRNAs upregulated after drug treatment. Methylation-specific PCR (MSP) and bisulfite pyrosequencing were carried out to analyze methylation status of the miRNA genes in bladder cancer cell lines and primary bladder cancer specimens.
Results: Of 664 miRNAs examined, 208 miRNAs were up-regulated (&gt;5-fold) in T24 cells, and 200 miRNAs were up-regulated in UM-UC3 cells, respectively. Among the miRNAs, 146 were commonly up-regulated in both T-24 and UM-UC3 cells. Among those 146 miRNAs, 36 miRNAs contain CpG islands in their 5’ end of the genes, and further analyzed. Methylation-specific PCR (MSP) was carried out, and 12 miRNAs showed aberrant methylation in bladder cancer cell lines. Bisulfite pyrosequencing of these 12 miRNAs was carried out, and we identified hypermethylation of 12 miRNAs in cultured and primary bladder cancer specimens.
Conclusions: Our results suggest that DNA methylation is associated with miRNAs silencing in bladder cancer, and that these miRNAs may have a role in the development and progression of 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 3954. doi:10.1158/1538-7445.AM2011-3954
Abstract 3957: Role of miRNA-211 in melanocyte and melanoma cells
Authors: Maddodi Nityanand D. , Madhavan Shajil , Devi Sulochana , Setaluri Vijayasaradhi 
Published: August 2014

Abstract
MicroRNAs (miRNAs) are regulatory RNAs that regulate gene expression. Evidence is accumulating that miRNAs are involved in almost all aspects of tumor biology including tumor cell survival, proliferation and migration. Here, we report that miRNA-221, which maps to the sixth intron of TRPM1 gene (a suppressor of melanoma metastasis), is highly expressed in melanocytes and its expression is reduced in primary and metastatic melanoma cell lines. Expression of miRNA-211 correlates with expression of TRPM1, a transient receptor potential family member calcium channel protein that we showed to be involved in regulation of melanocyte calcium homeostasis and melanin pigmentation. TRPM1and miRNA-211 expression are significantly lower in rapidly proliferative melanocytes compared to the slow growing, differentiated melanocytes. Expression of RAB22A (member of the RAS family of small GTPases), a predicted RNA target of miRNA-211is inversely correlated with the expression of miRNA-211and TRPM1 in melanocytes. Inhibition of miRNA-211 expression by anti-miR211 inhibited the growth of rapidly growing melanocytes. Ectopic expression of miRNA-211in melanoma cells inhibit growth and reduced their migration. We propose that activation of endogenous miRNA-211 expression or targeted delivery of miR-211 in melanoma is a potential therapeutic option for treatment of cutaneous melanoma.
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 3957. doi:10.1158/1538-7445.AM2011-3957
Abstract 3958: A miRNA inhibitor screen for synthetic lethal interactions in KRAS-driven NSCLC
Authors: Borkowski Robert , Du Liqin , Minna John D. , Gazdar Adi F. , Pertsemlidis Alexander 
Published: August 2014

Abstract
Lung cancer, especially non-small cell lung cancer (NSCLC), is currently the leading cause of cancer fatalities in the United States, accounting for 30% of the fatalities in males, and 26% in females. Additionally, the five-year survival rate for individuals affected by lung cancer has only improved by 3% in the past 35 years. As suggested by the survival data, very few effective treatment options are available for NSCLC, and many vary dramatically in efficacy depending on the genetic status of the tumor. In particular, the presence of mutant KRAS in NSCLC serves as a negative predictor for drug efficacy. KRAS mutations are found in ∼22% of NSCLC tumors, and tumors harboring these mutations are especially refractory to treatment.
We have identified synthetic lethal miRNAs in the background of KRAS-dependence through a four-armed miRNA inhibitor screen. A miRNA inhibitor screen can serve to not only identify miRNAs involved in context-dependent survival, but also genes and pathways that would be obscured by genomic redundancy in a conventional RNAi screen. Using a comprehensive library of miRNA inhibitors coupled with an endpoint assay for cell viability, we can identify miRNAs that modulate viability or paclitaxel sensitivity in KRAS-dependent NSCLC cell line NCI-H358 with minimal effect in the wild-type KRAS cell line NCI-H1993. Candidate miRNAs are validated in an expanded panel of ten cell lines including four KRAS mutant, four KRAS wild-type, and two immortalized human bronchial epithelial cell lines. The miRNAs identified here will allow us to elucidate vulnerable pathways in KRAS-dependent tumors that can be exploited for a therapeutic or predictive benefit in a typically difficult to manage class of tumor.
This research was supported by NIH R01 CA129632 from the National Cancer Institute and by P50 CA70907 from the UT Southwestern/MD Anderson Cancer Center Lung Specialized Program of Research Excellence.
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 3958. doi:10.1158/1538-7445.AM2011-3958
Abstract 3959: Growth suppression by TGF-β in responsive colon carcinoma is opposed by miR-20a through mechanisms altering p21WAF1 up-regulation
Authors: Sokolova Viktorija , Fiorino Antonio , Reid James F. , Crippa Elisabetta , Pierotti Marco A. , Gariboldi Manuela 
Published: August 2014

Abstract
Loss of response to TGF-β occurs in many cancers and disruption of its regulatory circuitry appears as a central event in the genesis of colorectal cancer (CRC) malignancy. Lack of inhibitory response to TGF-β is common to most colon cancer cell lines. However, inactivating mutations at receptors and transducers occur in less than a half of neoplastic colon tissues, which underscore the significance of additional mechanisms diverting TGF-β growth suppression. In this context, abrogation of TGF-β response by some miRNAs has been recently reported.
By searching for miRNAs in regions showing copy number changes and concordant gene expression in 36 sporadic CRCs compared to their normal counterpart, we identified the miR-17-92 cluster on the 13q31 locus, which is gained and highly expressed at early stages of CRC. MiR-20a from miR-17-92 cluster is a paralog of the miR-106b, which affects TGF-β sensitivity in gastric carcinoma. We hypothesized an involvement of miR-20a in the suppression of TGF-β response in CRCs and selected the TGF-β sensitive FET colon carcinoma, expressing low miR-20a levels, to investigate the relationship between enhanced expression of miR-20a and TGF-β sensitivity and address growth inhibition.
We report that miR-20a affects regulation of p21WAF1 expression, has a negative and significant effect on the cytostatic response mediated by TGF-β – evaluated by BrdU incorporation, MTT assay, and cell-cycle analysis – but shows little effect on TGF-β untreated cells. Although p21WAF1 transcript and protein are significantly decreased in cells treated or not with the cytokine, we could observe that the p21 up-regulation driven by TGF-β is strongly subverted by miR-20a. One potential mechanism of p21 down-modulation by miR-20a can be the targeting of its 3’UTR, as occurring for miR-106a. Moreover, we could observe that miR-20a is also able to block the transactivation of the 2.3-kb p21 promoter upon TGF-β stimulation, as assessed by luciferase-based assay, but not the activation of the Smad3/4-reponsive reporter. Down-modulation of c-Myc by TGF-β, crucial to regulation of p21 transcription, is also subverted by miR-20a delivery into cells.
Our experiments suggest for miR-20a an interference with the TGF-β homeostasis in colon addressing the up-regulation of p21 expression, through mechanisms involving more effectors of the TGF-β cascade. Overall, miR-20a seems to participate in the abrogation of this key regulatory response in colonic epithelium.
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 3959. doi:10.1158/1538-7445.AM2011-3959