bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3931: Generation of tumorgraft models to characterize novel tumor suppressor genes implicated in lung carcinogenesis
Authors: Pereira Carolina , Gimenez-Xavier Pol , Gomez Gonzalo , Condom Enric , Villanueva Alberto , Pisano David , Sanchez Cespedes Montse 
Published: August 2015

Abstract
The extremely poor prognosis and lack of efficient treatments throw lung cancer (LC) to the top of the deadliest types of cancer worldwide. Throughout the years, the role played by host genetic variation has been constantly highlighted as the key in determining tumor onset and progression. In this regard, the discovery of LC-related genes paved the way to the development of targeted therapies that nowadays are benefiting patients harboring specific mutational patterns, such as EGFR mutations or ALK rearrangements.
Here, aiming to characterize novel tumor suppressor genes in LC, 8 patient-derived tumors were subcutaneously or orthotopically engrafted in nude mice for growing and subsequently carry out exome and transcriptome sequencing. The strategy avoided the common admixture exhibited by the presence of normal cells in the sample, which were successfully swept away in the engrafting step, as determined by microsatellite analyses. Among the 4430 mutations detected by exome-seq, we focused on the 79 ones that would presumably lead to biallelic gene inactivation, a common feature exhibited by tumor suppressors: homozygous frameshift indels, nonsense and splicing site mutations. We then chose to characterize one particular candidate gene, which codifies for a globular protein that might be involved in the ability of tumors to escape the action of the immune system. The genetic screening performed resulted in a mutation rate of 5.1% in 79 tested LC cell lines and of 3.9% in a panel of 179 lung primary tumors. The complete coding region was cloned in constitutive and inducible systems in order to restore the expression of the protein in gene-depleted LC-cell lines, and preliminary results pinpoint that it may indeed trigger an anti-tumoral effect. This in vitro approach is currently ongoing and hopefully, will enlighten us about its tumor suppressive potential in the near future.
Citation Format: Carolina Pereira, Pol Gimenez-Xavier, Gonzalo Gomez, Enric Condom, Alberto Villanueva, David Pisano, Montse Sanchez Cespedes. Generation of tumorgraft models to characterize novel tumor suppressor genes implicated in lung carcinogenesis. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3931. doi:10.1158/1538-7445.AM2015-3931
Abstract 3932: Using Sleeping Beauty transposon mutagenesis to identify CRC driver genes
Authors: Wei Zhubo , Takeda Haruna , Copeland Neal G. , Jenkins Nancy A. 
Published: August 2015

Abstract
In order to better understand the initiation and development of colorectal cancer (CRC), Sleeping Beauty (SB) transposon mutagenesis screens were performed in mice with mutations in genes that play important roles in differen stages of CRC. Functional validation assays, including invasion assay and xenograft assay, were carried out for the candidate genes that were selected by their potentials in tumor progression and/or human CRC. We identified six genes driving malignant tumor progression, and a new human CRC tumor suppressor gene, ZNF292, that may also function in other types of cancer. More detailed investigations are being done for those identified genes, including experiments using knockout mice. Our study provides a resource for the development of new CRC therapies.
Citation Format: Zhubo Wei, Haruna Takeda, Neal G. Copeland, Nancy A. Jenkins. Using Sleeping Beauty transposon mutagenesis to identify CRC driver genes. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3932. doi:10.1158/1538-7445.AM2015-3932
Abstract 3943: Genetic abnormalites in hypoxia sensing regulators cause human pheochromocytoma/paraganglioma and plolycythemia syndrome
Authors: Yang Chunzhang , Wang Herui , Pacak Karel , Zhuang Zhengping 
Published: August 2015

Abstract
Hypoxia inducible factors (HIFs) control the cellular response to hypoxia and when dysregulated, contribute to tumorigenesis. In the presence of oxygen, HIFs are strictly deactivated via EGLN/VHL/26S proteasome degradation mechanism. We identified that either gain-of-function mutations in HIF2A, or loss-of-function mutations in EGLN1/2, result in the multiple pheochromocytomas or paraganglioma associated with polycythemia. Mutation in HIF2A or EGLN1/2 cause compromised interaction of prolyl hydroxylase to HIF-α and lead to defects of HIF-α degradation. Stabilized HIF-α translocates into cell nucleus and function as a potent transcriptional factor, which induces constitutive transcriptional activation of hypoxia related genes, as well as pseudohypoxic change in cellular signaling and metabolism. Our finding provided direct evidence that genetic defect in intrinsic HIF-α and its regulatory proteins EGLN1/2 can be a key factor involved in the pathogenesis of this tumor-associated syndrome.
Citation Format: Chunzhang Yang, Herui Wang, Karel Pacak, Zhengping Zhuang. Genetic abnormalites in hypoxia sensing regulators cause human pheochromocytoma/paraganglioma and plolycythemia syndrome. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3943. doi:10.1158/1538-7445.AM2015-3943
Abstract 3946: Secretory ANXA3 endows liver cancer cells with tumorigenic and self-renewal abilities and promotes HCC development
Authors: Tong Man , Ma Stephanie 
Published: August 2015

Abstract
Hepatocellular carcinoma (HCC) is the third leading cause of mortality in Southeast Asia and in Hong Kong. Despite advances in treatment, the prognosis of advanced HCC patients remains dismal. Contemporary challenge in treating HCC has been the common chemotherapy resistance and recurrence after therapy.Therefore, the identification of valid targets and the development of new therapies are urgently needed for more effective clinical management of this deadly disease. We found secretory annexin A3 (ANXA3) to be up-regulated in HCC cell lines, compared with immortalized normal liver cell line MIHA. Clinically, secretory ANXA3 levels in the serum were found to be progressively elevated from non-HCC individuals to early and advanced HCC patients, with up-regulation of serum ANXA3 to be tightly associated with gender, number of tumor nodules, tumor sizes and tumor stages. More importantly, the diagnostic value of secretory ANXA3, as evident by ROC analysis, was found to be more superior to the commonly used biomarker alpha-fetoprotein (AFP). Subsequent functional studies found secretory ANXA3 to promote cancer and stem cell-like properties of HCC cells. Co-culture of conditioned medium from ANXA3-overexpressing cells with ANXA3-absent HCC cells potentiated the abilities of HCC cells to migrate, invade, self-renew, induce tube formation in endothelial cells, and resist apoptosis induced by staurosporine and chemotherapy. The in vivo tumor-initiating capacity was also significantly enhanced in HCC cells when co-cultured with ANXA3-containing conditioned medium compared with conditioned medium from cells transfected with empty vector control. Similar functional properties were also observed when MIHA cells were treated with recombinant ANXA3 proteins. In an effort to characterize the molecular mechanism by which ANXA3 drives cancer and stem cell-like properties in HCC, cDNA microarray profiling was performed to compare the gene expression between ANXA3-depleted and control cells. Pathway enrichment analysis found many of the deregulated genes to be closely associated with the JNK/AP-1 signaling cascade. Activation of JNK pathway was detected when cells were treated with recombinant ANXA3 proteins or ANXA3-containing conditioned medium. Collectively, our findings suggest that secretory ANXA3 plays pivotal roles in promoting tumor initiation, growth and chemoresistance through the activation of JNK signaling pathway in HCC.
Citation Format: Man Tong, Stephanie Ma. Secretory ANXA3 endows liver cancer cells with tumorigenic and self-renewal abilities and promotes HCC development. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3946. doi:10.1158/1538-7445.AM2015-3946
Abstract 3953: HORMAD1 plays an important role in the HNSCC carcinogenesis
Authors: Carlin Viviane , Rodrigues-Junior Dorival Mendes , Biassi Thais Priscila , Nozima Bruno Heidi Nakano , Buri Marcus Vinicius , Vettore Andre Luiz 
Published: August 2015

Abstract
Head and neck squamous cell carcinoma (HNSCC) is the sixth leading cause of cancer worldwide. Approximately one-third of patients present with early-stage disease and these patients are treated with either surgery or radiotherapy, with cure rates of 70-90%. The majority of patients, however, present with locally advanced stage disease. Radical treatment in this situation requires multimodality therapy with surgery, commonly followed by postoperative radiotherapy or chemotherapy. These treatments are intensive and associated with severe acute toxicity and long-term sequelae. Despite recent advances in both surgical and radiotherapy delivery techniques, up to 50% of locally advanced tumours relapse usually within the first 2 years after treatment. The development of novel therapeutic approaches and their integration into the current forms of treatment is of great interest to improve the therapeutic efficacy. Immunotherapy may provide an alternative for current treatment approach. Cancer/testis antigens (CTAs) are a family of tumor-associated antigens expressed in human tumors of different histological origin, but not in normal tissues except for testis and placenta. This tumor-restricted pattern of expression, together with their strong in vivo immunogenicity, identified CTA as ideal targets for tumor-specific immunotherapeutic approaches. A screening for CTAs expressed in HNSCC detected HORMAD1 recurrently expressed in these tumors. Objectives: The aim of this study is better understand the role of HORMAD1 in HNSCC by evaluating its influence in different tumorigenic processes, such as apoptosis, cell cycle and migration. Methods: The HORMAD1 expression was evaluated in HNSCC cell lines by RT-PCR and the presence of HORMAD1 protein was confirmed by Western Blot. HORMAD1 expression was silenced by shRNA and assays were conducted to evaluate the impact of HORMAD1 absence in cell cycle regulation and apoptosis. Results: The HORMAD1 gene was knocked-down in a HNSCC cell line and functional assays revealed a reduction in the proportion of the cells in the G1 phase of cell cycle and an induction of the apoptosis when HORMAD1 is absent. Conclusions: Our results demonstrate that HORMAD1 is frequently expressed in HNSCC and our in vitro observations indicate that this CTA may play an important role in the HNSCC carcinogenesis.
Citation Format: Viviane Carlin, Dorival Mendes Rodrigues-Junior, Thais Priscila Biassi, Bruno Heidi Nakano Nozima, Marcus Vinicius Buri, Andre Luiz Vettore. HORMAD1 plays an important role in the HNSCC carcinogenesis. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3953. doi:10.1158/1538-7445.AM2015-3953
Abstract 3960: The role and therapeutic potential of miRNAs in colorectal liver metastasis
Authors: Sahu Smiti Snigdha , Nabinger Sarah , Guanglong Jiang , Bates Allison , Lee Sangbin , Hiromi Tanaka , Liu Yunlong , Kota Janaiah 
Published: August 2015

Abstract
Colorectal cancer (CRC) is a leading cause of cancer related deaths worldwide. Liver metastasis occurs in 60% of CRC patients and usually responds poorly to treatment - contributing to mortality rate. MicroRNAs (miRNAs) are highly conserved, endogenously encoded small, non-coding RNA molecules regulating global gene expression. Their role in cancer pathogenesis, including CRC, has been well documented. Detailed miRNA expression analysis on a large cohort of CRC tumors is needed to identify clinically relevant miRNAs and explore their potential to target liver metastases.
We analyzed miRNA expression data of 406 CRC tumors from publically available CRC genome sequencing project and identified 58 miRNAs, which were significantly downregulated. Using miRNA target prediction analysis, 10 miRNAs were selected for further studies as they were either known to target genes in cellular pathways associated with CRC liver metastases, or located within a chromosomal loci commonly lost in colorectal liver metastases. qPCR analysis of these 10 selected miRNAs in primary and colorectal liver metastasis tissues and in CRC cell lines demonstrated four miRNAs; miR-132, miR-378f, miR-605, and miR-1976 that are significantly down-regulated with &lt;2 fold change (p&gt;0.05). To investigate the anti-tumorigenic and metastatic properties of miR-132, -378f, -605, and -1976, we transfected 3 different CRC cell lines (SW620, HCT-116, and CT-26) with miR-mimics and subjected them to cell proliferation, apoptosis, soft agar, invasion, and migration assays. Ectopic expression of miR-378f, -605, and -1976 suppressed CRC cell proliferation, anchorage independent growth, migration, and invasion and increased apoptosis. Interestingly, CRC patients with high miR-378f and miR-1976 had better survival compared to low expressing patients (p&lt;0.044).
In conclusion, our in vitro findings suggest anti-tumorigenic/metastatic properties of miR-378f, -605, and -1976 in CRC. A further understanding of their function and in vivo therapeutic evaluation may help in developing novel therapeutic strategies for this malignancy.
Citation Format: Smiti Snigdha Sahu, Sarah Nabinger, Jiang Guanglong, Allison Bates, Sangbin Lee, Tanaka Hiromi, Yunlong Liu, Janaiah Kota. The role and therapeutic potential of miRNAs in colorectal liver metastasis. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3960. doi:10.1158/1538-7445.AM2015-3960
Abstract 399: Nanoparticle silencing of β1 and β3 integrins augments Dasatinib sensitivity
Authors: Parvani Jenny G. , Chu Vinson , Roelle Sarah , Lu Zheng-Rong , Schiemann William 
Published: August 2015

Abstract
Triple negative breast cancers (TNBCs) are an aggressive subcategory of breast cancers that currently lack FDA-approved targeted therapies. Previous studies have i) further subcategorized TNBCs into 5 distinct subtypes, each with a preferential response to specific chemotherapies and ii) identified beta1 and beta3 integrins to be key mediators of breast cancer EMT and metastasis. We surveyed beta1 and beta3 integrin expression in the 5 subtypes of TNBC with and without treatment of their proposed chemotherapies by western blot analysis. Using nanoparticles, we delivered beta1 and beta3 integrin-specific siRNAs to silence the expression of both integrins either with or without treatment of the proposed chemotherapies, and evaluated the effect of these treatment regimens on EMT, invasion, and 3D outgrowth. We demonstrated that beta1 and beta3 integrins are robustly expressed in the Mesenchymal Stem-Like, Mesenchymal, and Basal-Like2 subtypes of TNBCs. Furthermore, we observed elevated expression of beta1 integrin upon Dasatinib treatment of the Mesenchymal Stem-Like subtype. Lastly, we determined that delivery of beta1 and beta3 integrin siRNAs sensitized breast cancer cells to Dasatinib treatment. Collectively, our data suggests that delivery of beta1 and beta3 integrin-specific siRNAs in combination with Dasatinib treatment efficiently eliminates the aggressive characteristics of Mesenchymal Stem-Like breast cancer cell lines.
Citation Format: Jenny G. Parvani, Vinson Chu, Sarah Roelle, Zheng-Rong Lu, William Schiemann. Nanoparticle silencing of β1 and β3 integrins augments Dasatinib sensitivity. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 399. doi:10.1158/1538-7445.AM2015-399
Abstract 3999: MicroRNA expression links obesity and recurrence in renal cell carcinoma
Authors: Shu Xiang , Hildebrandt Michelle A. , Gu Jian , Tannir Nizar M. , Matin Surena , Karam Jose A. 
Published: August 2015

Abstract
Obesity is an established risk factor for clear cell renal cell carcinoma (ccRCC) development and prognosis; however, the mechanisms underlying this link remain unclear. In the present study, we set to assess whether microRNAs (miRNAs) can serve as a molecular link between obesity and recurrence in ccRCC. Through bioinformatics tools and literature search, we identified 126 obesity-related miRNAs. Supplemented with 25 miRNAs which were differentially expressed between ccRCC from normal kidney, we tested the association of these miRNAs with ccRCC recurrence. Significantly decreased levels of hsa-miR-204-5p were found in recurrent ccRCC patients with an over 2-fold increased risk of recurrence (HR = 2.15, p = 0.028, MST = 25.6 vs. 47.2 months). Correlations between miRNA expression and the predicted target genes were tested using gene profiling data generated from these same patients. We found strong inverse correlations between miR-204 expression and several obesity-related genes, including IGF2BP2 (r = -0.40, p = 4.14×10−4), a member of the insulin growth receptor signaling pathway. This correlation was further validated in TCGA data (r = -0.58, p = 1.40×10−22). We also found that low level of hsa-miR-139-5p was significantly associated with increased recurrence risk (HR = 2.37, p = 0.026, MST = 32.2 vs. 51.3 months). In conclusion, we found a set of obesity-related miRNAs that are dysregulated in ccRCC tissues, and some of these miRNAs, such as hsa-miR-204-5p, were associated with the recurrence of RCC, potentially through regulating obesity-related gene expression.
Citation Format: Xiang Shu, Michelle A. Hildebrandt, Jian Gu, Nizar M. Tannir, Surena Matin, Jose A. Karam. MicroRNA expression links obesity and recurrence in renal cell carcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3999. doi:10.1158/1538-7445.AM2015-3999
Abstract 4009: Comparative microRNA profiling of prostate carcinomas with increasing tumor stage by deep-sequencing
Authors: Nolte Elke , Hart Martin , Wach Sven , Szczyrba Jaroslaw , Taubert Helge , Rau Tilman , Hartmann Arndt , Grässer Friedrich A. , Wullich Bernd 
Published: August 2015

Abstract
Background: MicroRNAs (miRNAs) are short, non-coding RNAs that post-transcriptionally regulate gene expression and play an important role in tumorigenesis. Previous deep-sequencing identified the microRNA profile of prostate carcinoma (PCa) vs. non-malignant prostate tissue. As an extension of our recent analyses, we now compared organ-confined prostate tumors (pT2), tumors with extra capsular growth (pT3, pN0), and lymph node metastasizing (pN1) PCa relative to corresponding non-malignant prostate tissue and healthy prostate tissue.
Material and Methods: We performed comparative miRNA expression profiling using deep sequencing of cDNA libraries. Potential target genes of deregulated miRNAs were identified by database analysis and subsequently validated in vitro using reporter gene constructs. miRNA and mRNA expression was determined using quantitative real-time PCR.
Results: The miRNA expression from the healthy and non-malignant tissue is consistent with our previous findings, indicating a high fidelity of the method employed. Some miRNAs (miR-375, miR-148a, miR-141 and miR-21) are expressed at increasing levels with increasing tumor stage, while other miRNAs (miR-200b/c, miR-25, miR-17 or miR-93) are up-regulated only from organ-confined tumors (pT2) to tumors with extra-capsular growth (pT3) but then expressed at lower levels after the transition to lymph node metastasizing tumors (pN0 vs. pN1). The same trend was seen in qRT-PCR analysis but due to the limited sample number, no significance was reached. Interestingly, miR-375, found to be up-regulated in tumor vs. normal tissue, and miR-15a, found induced by sequencing in T2 and T3 tumors but not in lymph node metastasizing tumors, target the phosphatases PHLPP1 and PHLPP2, respectively. PHLPP1 and PHLPP2 dephosphorylate members of the AKT-family of signal transducers thereby inhibiting cell growth. Co-expression of miR-15a and miR-375 resulted in down-regulation of PHLPP1/2 and a strongly increased PCa cell growth.
Conclusion: miRNA profiling of pT2 (pN0), pT3 (pN0), and lymph node metastasizing prostate carcinoma (pN1) by deep sequencing revealed clearly changed miRNA levels.
Citation Format: Elke Nolte, Martin Hart, Sven Wach, Jaroslaw Szczyrba, Helge Taubert, Tilman Rau, Arndt Hartmann, Friedrich A. Grässer, Bernd Wullich. Comparative microRNA profiling of prostate carcinomas with increasing tumor stage by deep-sequencing. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4009. doi:10.1158/1538-7445.AM2015-4009
Abstract 4032: Functional analysis of exosomes derived from human esophageal squamous cell carcinoma
Authors: Matsumoto Yasunori , Kano Masayuki , Akutsu Yasunori , Nishimori Takanori , Hanari Naoyuki , Hoshino Isamu , Murakami Kentaro , Toyozumi Takeshi , Suito Hiroshi , Takahashi Masahiko , Sekino Nobufumi , Nabeya Yoshihiro , Matsubara Hisahiro 
Published: August 2015

Abstract
Exosomes are small membrane vesicles (30-100 nm) released by many types of cells including cancer cells, and are thought to play an important role in cell-to-cell communications. Exosomes contain lipids, proteins, and nucleic acids such as mRNAs or microRNAs, they are tought to have relationship with tumor growth or metastasis. Our laboratory was previously reported the level of microRNA-1246, expressed mainly in tumor tissues of esophageal squamous cell carcinoma (ESCC), was significantly high in exosomes extracted from the serum of ESCC patients. However, the exosome dynamics and transportation between cancer cells and the other cells are still unclear. In this study, we assessed the cell-to-cell communication via exosomes with fluorescent imaging and analyzed the effect of cancer cell derived exosome to tumor progression.
In order to image and analyze the movement of cancer cell-derived exosomes, green fluorescent protein (GFP)-tagged CD63, which is a general marker of exosomes, was expressed in human esophageal squamous cancer cell line TE2. Exosomes were extracted from supernatant with ultracentrifuge method. Extracted GFP-tagged exosomes were added to the other cells to obtain the images of transportation. The effects of exosomes to tumor progression were also assessed with cell proliferation assay, invasion oassay, and migration assay. Our data indicates that cancer cell derived exosomes affect tumor progression.
Citation Format: Yasunori Matsumoto, Masayuki Kano, Yasunori Akutsu, Takanori Nishimori, Naoyuki Hanari, Isamu Hoshino, Kentaro Murakami, Takeshi Toyozumi, Hiroshi Suito, Masahiko Takahashi, Nobufumi Sekino, Yoshihiro Nabeya, Hisahiro Matsubara. Functional analysis of exosomes derived from human esophageal squamous cell carcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4032. doi:10.1158/1538-7445.AM2015-4032