bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3167: miR-138 and its role in melanoma progression
Authors: da Cruz Adriana T. , Hunger Aline , Morais Alice Santana , Meliso Fabiana Marcelino , Staruss Brayn , Jasiulionis Miriam Galvonas 
Published: August 2012

Abstract
miRNAs are non-coding RNAs that bind to mRNA targets preventing their translation. It is predicted that over 30% of mRNAs are regulated by miRNAs. Therefore these molecules are considered essential to many biological responses, such as cell proliferation, apoptosis and stress responsiveness. Loss or gain of miRNAs function contributes to development of many diseases, included cancer. Melanoma rises from malignant transformation of melanocytes. Despite being rare, it is responsible for the greatest number of deaths promoted by all skin cancers. One reason for this scenario is that melanoma metastatic is usually incurable. To determine the role of miRNAs in melanoma progression, the expression of several miRNAs were evaluated in a murine model that mimics different stages of the genesis of this tumor. In that model, several cell lines were obtained after submitting melan-a melanocytes to sequential cycles of anchorage blockade. Among miRNAs in which expression were altered, miR-138 has decreased expression in intermediate phases of melanoma genesis and was selected for further investigation. It was verified that mRNA of p53, Ezh2, MyoD and Sirt-1 are putative targets of miR-138. Interestingly, these mRNAs also have inverse expression of miR-138 in the distinct lineages of this model. Luciferase assay was done to confirm if miR-138 directly regulate such mRNAs. Super expression of miR-138 in the cell lineages that have lower levels of this miRNA was also induced. Functional experiments assessing proliferation rate, migration and invasiveness capacity in these cells expressing ectopic miR-138 were performed. The results indicate that miR-138 deregulation is an important event of melanoma progression. The targets of this miRNA are key components in pathways frequently disrupted in cancer, like cell cycle and apoptosis control, epithelial to mesenchymal transition regulation, and differentiation process. Thus, miR-138 represents a strong candidate to therapeutic target. The exploration of its role can contribute to improve the comprehension about melanoma progression and elucidate new ways of interventions against cancer. Supported by FAPESP.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3167. doi:1538-7445.AM2012-3167
Abstract 3169: MicroRNA-144 induces proliferation and invasion in nasopharyngeal carcinoma through repression of PTEN
Authors: Zhang Li Yi , Fu Li , Guan Xin Yuan 
Published: August 2012

Abstract
Nasopharyngeal carcinoma (NPC) is a characteristic type of head and neck cancer which is frequent in Southern China. Different from other head and neck cancers, tumor suppressor genes (TSGs) mutation and deletion in NPC is uncommon. Conversely, downregulation of TSGs expression by miRNA is increasingly recognized as an important mechanism of nasopharyngeal tumorigenesis. In this study, we report that miR-144 is commonly upregulated in NPC specimens and NPC cell lines, its repression decreased cell proliferation, clonogenicity, migration, invasion and tumor growth, establishing an important oncogenic role for this miRNA. Further, we verified tumor suppressor gene PTEN as a direct target through luciferase reporter assay in NPC cell lines. Similar to the restoring miR-144 expression in miR-144 attenuated cells, PTEN downregulation in miR-144 attenuated cells increase cell growth and invasion. Mechanistic investigations revealed that miR-144 suppressed the expression of PTEN to downregulate p53 while suppressing the expression of pAKT and cyclin D1 induce G1-phase cell-cycle arrest. Taken together, our results indicate that miR-144 functions as an onco-miRNA in NPC, and its onco-effects are mediated chiefly by repressing PTEN expression.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3169. doi:1538-7445.AM2012-3169
Abstract 3170: Comprehensive analysis of the microRNA-128 function in head and neck squamous cell carcinoma
Authors: Hauser Belinda , Pang Xiaowu , Fang Yayin , Gu Xinbin 
Published: August 2012

Abstract
MicroRNAs are 22∼nucleotide-long endogenously expressed, highly conserved noncoding RNAs with important regulatory functions in proliferation, apoptosis, and metastasis. miR-128 a brain-enriched, which is transcribes from two gene copies (miR-128-1 and miR-128-2) on chromosome 2 and chromosome 3 which produce identical mature forms. miR-128 is most commonly in gliomas that have shown to function as a tumor suppressor which inhibits cell proliferation. Proteomic alterations of prostate cancer show miR-128 to down regulate cell invasiveness. Here we evaluated the role of miRNA-128 in HNSCC, to identify its putative targets and elucidate the possible mechanisms underlining the function of miR-128 in HNSCC. We established HNSCC cell lines that stably expressed individual members of the miR-128 using a lentiviral delivery system. The levels of miR-128 and their targeted proteins were analyzed by qRT-PCR and Western blot. miR-128 affinity was elucidated by MTT, colony formation, flow cytometry, and a tumor xenograft model. Two kinds of stably transfected HNSCC cell lines, including JHU-22miR-128 transfected with miR-128 and a vector control cell line JHU-22vector, were generated as a testing system. The miR-128 level in the JHU-22miR-128 cells was eleven fold higher than in JHU-22vector cells. We found that overexpression of miR-128 enable to effectively suppress cell viability (30%), decrease of proliferation (55%), and significantly reduced solid tumor growth in tumor xenografts models compared to the control groups. Transfected miR-128 cells exhibited astrocyte morphology. The inhibition mechanism of miR-128 was determined by evaluating five putative targets (BMI-1, BAG2, BAX, H3f3b, and Paip2) of miR-128. Overall, miR-128 enables to directly inhibit all these targets, but the binding affinity of miR-128 is dominantly towards to BMI-1 and BAG-2 targets. Conclusions: miR-128 exhibits anti-proliferative effects and phenotypic alteration in HNSCC by targeting multiple predicted conserved targets activity function in apoptosis, cell cycle, transcription, and translation. Our results provide a better understanding of miR-128 function in HNSCC and the potential targets to develop novel diagnostic markers and targeted therapy.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3170. doi:1538-7445.AM2012-3170
Abstract 3224: Pre-clinical targeting of the metabolic phenotype of lymphoma by AZD3965, a selective inhibitor of monocarboxylate transporter 1 (MCT1)
Authors: Critchlow Susan E. , Hopcroft Lorna , Mooney Lorraine , Curtis Nicola , Whalley Nicky , Zhong Haihong , Logie Armelle , Revill Mitchell , Xie Liang , Zhang Jingchuan , Yu De-Hua , Murray Clare , Smith Paul D. 
Published: August 2012

Abstract
Introduction - The metabolic phenotype of tumours (relative to most normal tissues) is shifted from oxidative phosphorylation to aerobic (Warburg Effect) or anaerobic glycolysis. This enables tumours to meet their energetic and biosynthetic demands even under conditions of low nutrient and O2. The end-product of glycolysis is lactate, a metabolic dead end, which if allowed to accumulate in the tumour cell may cause feedback inhibition of glycolysis and intra-cellular acidification resulting in inhibition of cell growth or survival. Experimental data - We have studied the effects of a potent, selective and orally available inhibitor of MCT1 in lymphoma cell lines and in vivo models. AZD3965 is a small molecule inhibitor of MCT1 with a binding affinity of 1.6 nM, is 6 fold selective over MCT2 and does not inhibit MCT4 at 10 μM. Both lactate transport and cell growth are potently inhibited by AZD3965 in lymphoma cell lines that preferentially express MCT1. Lactate transport inhibition in some cell lines also induces a cytotoxic effect. In vitro combination studies show that lactate transport inhibition can enhance the induction of cell death by doxorubicin. Blocking lactate transport in vitro also leads to a rapid inhibition of glucose uptake in the Raji Burkitt's lymphoma cell line. In vivo, AZD3965 is well tolerated and induces a dose and time dependent accumulation of lactate in the tumours, suppresses tumour growth and in the Raji model potentiates the effects of Rituxan, doxorubicin and bendamustine. Conclusions - Here we demonstrate that selective inhibition of lactate transport by the MCT1 inhibitor AZD3965 offers an novel mechanism for targeting the metabolic phenotype in tumours that preferentially express MCT1.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3224. doi:1538-7445.AM2012-3224
Abstract 3249: Intersectin 1 is required for neuroblastoma tumorigenesis
Authors: Russo Angela , O'Bryan John P. 
Published: August 2012

Abstract
Neuroblastoma (NB) is a malignant tumor deriving from the neural crest and is responsible for 13% of cancer-related deaths in children. Phosphoinositide 3-kinases (PI3Ks) play a central role in NB tumorigenesis. PI3Ks activate AKT, which regulates survival and stabilizes the MYCN oncogene. Both MYCN and AKT are markers for poor prognosis in NBs. Inhibiting PI3Ks with pan-inhibitors blocks malignant progression in vivo; however, these inhibitors have high toxicity that limits their use in NB treatment. Though there are three classes of PI3Ks, only Class I isoforms have been implicated in NB tumorigenesis. We have previously found that the scaffold protein intersectin 1 (ITSN1) interacts with PI3KC2α and regulates its activation as well as AKT activation in neuronal cell lines. In addition, ITSN1 overexpression is transforming in rodent fibroblasts. Thus, we examined the role of the ITSN1-PI3KC2α pathway in human NB tumorigenesis. ITSN1 and PI3KC2α are highly expressed in primary human neuroblastoma tumors of varying stage and MYCN amplification status. In addition, both ITSN1 and PI3KC2α are expressed in NB tumor cell lines derived from high grade NB tumors. Silencing ITSN1 dramatically inhibited the anchorage-independent growth of NB tumor cells in vitro and tumor formation in xenograft assays in vivo independent of MYCN status. Conversely, heterologous overexpression of ITSN1 increased the formation of soft agar colonies. These results suggest that ITSN1 functions as an oncogene in NB cells. Furthermore, PI3KC2α overexpression restores anchorage-independent growth of ITSN1-depleted NB cells demonstrating that PI3KC2α mediates ITSN1's tumorigenic properties. This study reveals a new pathway, i.e., ITSN1-PI3KC2α, involved in regulating the pathogenesis of NBs and suggests that this pathway may represent a new target for therapeutic intervention in the treatment of NB patients.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3249. doi:1538-7445.AM2012-3249
Abstract 3394: Identification of PRDX4 and P4HA2 as metastasis-associated proteins in oral cavity squamous cell carcinoma by comparative tissue proteomics of microdissected specimens using iTRAQ technology
Authors: Chang Kai-Ping , Chang Yu-Sun , Yu Jau-Song , Chi Lang-Ming 
Published: August 2012

Abstract
Background Cervical lymph node metastasis represents the major prognosticator for oral cavity squamous cell carcinoma (OSCC). Methods Here, we used an iTRAQ-based quantitative proteomic approach to identify proteins that are differentially expressed between microdissected primary and metastatic OSCC tumors. The selected candidates were examined in tissue sections via immunohistochemistry, and their roles in OSCC cell function investigated using RNA interference. Results Seventy-four differentially expressed proteins in nodal metastases, including PRDX4 and P4HA2, were identified. Immunohistochemical analysis revealed significantly higher levels of PRDX4 and P4HA2 in tumor cells than adjacent non-tumor epithelia (P &lt; 0.0001 and P &lt; 0.0001, respectively), and even higher expression in the 31 metastatic tumors of lymph nodes, compared to the corresponding primary tumors (P = 0.060 and P &lt; 0.0001, respectively). Overexpression of PRDX4 and P4HA2 was significantly associated with positive pN status (P = 0.048 and P = 0.041, respectively). PRDX4 overexpression was a significant prognostic factor for disease-specific survival in both univariate and multivariate analyses (P = 0.034 and P = 0.032, respectively). Additionally, cell migration and invasiveness were attenuated in OEC-M1 cells upon in vitro knockdown of PRDX4 and P4HA2 with specific interfering RNA. Conclusions Novel metastasis-related prognostic markers for OSCC could be identified by our approach.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3394. doi:1538-7445.AM2012-3394
Abstract 3398: High-throughput expression profiling of circulating tumor cells from breast cancer patients as potential therapy decision indicator
Authors: Kolostova Katarina , Romzova Marianna , Bobek Vladimir , Kubista Mikael , Kasimir-Bauer Sabine 
Published: August 2012

Abstract
Background: The aim of this study was to assess the molecular profiles of circulating tumor cells (CTCs) from metastatic breast cancer (MBC) patients and to evaluate their potential as prognostic and therapy indicators. Methods: Blood samples (5ml) of 77 MBC patients from Czech and German Gynecological Cancer Centers were analyzed for CTCs using the AdnaTest BreastCancer (AdnaGen AG, Germany) for the detection of EpCAM, MUC-1 and HER-2 transcripts. Obtained cDNA molecules have been gene-specifically pre-amplified for multimarker qPCR analysis measured on Biomark® (Fludigm, USA) microfluidic chip for 48 samples and 48 testing positions (in total: 2304 rxn, 31 tumor specific-genes, 30 MBC samples, respectively). qPCR- results have been analyzed by GENEX v.s. 5.0 software (MultiD, SE). Results: CTCs were found in 42% of the MBC patients. Based on the AdnaTest, two distinct groups of CTC positive-MBC patients have been identified after principal component analysis of the gene expression data. The first CTC-positive group had relatively high EPCAM, MUC1, KRT19, HER2, AURKA, and MCM expression. In contrast, expression of PTEN, SATB1 and CD45 was low. The second CTC-positive group showed lower expressions of AURKA, EPCAM, and KRT19 than the first group. Furthermore, markers typically expressed in CD45 positive cells like SATB1, AKT, PARP, PTEN, mTOR, but also oncogene MYC and tumor suppressor TP53 were highly expressed in this group. The samples of CTC-negative MBC patients were characterized by low expression of the cancer phenotype associated genes EPCAM, KRT19, and MUC1, but showed comparably higher expression of genes associated with a stem cell like phenotype such as TWIST, ALDH1 and CD24. Conclusions: Based on our data, we conclude that CTCs enriched by the AdnaGen-technology are heterogeneous and do not necessarily express EPCAM. Even CTCs with low EPCAM expression but with elevated KRT19 and AURKA levels may represent a subgroup of high risk metastatic BC patients. Follow-up of the patients will show whether specific gene profiles of CTCs will a) identify responders and non-responders to breast cancer related therapies and b) be useful for personalized therapy of MBC in the future.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3398. doi:1538-7445.AM2012-3398
Abstract 34: Inhibitory effects of betulinic acid isolated from Nelumbo nucifera (Lotus) on breast cancer-mediated bone destruction
Authors: Park Se-Young , Park Kwang-Kyun , Chung Won-Yoon 
Published: August 2012

Abstract
Most of cancer patients die, not because of the tumor in the primary site, but because of spreading to other site. In particular, bone metastasis is relatively common in patients with breast, prostate, and lung cancer. Many breast cancer patients suffer from bone metastasis with bone pain and pathological fractures. These metastases are predominantly osteolytic and develop when tumor cells interact with bone. Tumor and bone interact in a vicious cycle, where tumor-secreted factors stimulate bone cells, which in turn release growth factors and cytokines that act back on the tumor cells. Within the vicious cycle are many potential therapeutic targets for treatment of bone metastatic disease. Nelumbo nucifera (Lotus) has been known as a medicinal herb for treatment of cough, fever and hyperdipsia. Betulinic acid (BA) is a naturally occurring triterpenoid present in lotus. In this study, we found that BA reduced mRNA expressions of osteolytic factors in MDA-MB-231 human metastatic breast cancer cells. In particular, mRNA level of parathyroid hormone-related protein (PTHrP), the major component of vicious cycle within bone, was significantly inhibited by BA. Treatment with BA decreased receptor activator of nuclear factor kappa-B ligand (RANKL) /osteoprotegerin (OPG) ratio in PTHrP-treated human osteoblasts. In addition, BA dose-dependently inhibited the RANKL-induced osteoclast differentiation and bone resorption by reducing the secretion of matrix metalloproteinases (MMPs) and cathepsin K derived from osteoclasts, without any evidence of cytotoxicity. We further examined the effect of BA on ovariectomy-induced osteoporosis in mice. Serum levels of tartrate-resistant acid phosphatase isoform 5b, alkaline phosphate, calcium, osteocalcin and C-terminal telopeptide of type I collagen were significantly increased in ovariectomized (OVX) mice than in sham mice. BA inhibited increases in the serum levels of these osteoporotic markers in OVX mice. We analyzed bone volume, trabecular bone thickness, trabecular number and trabecular separation by micro-computer tomography (μ-CT) scanning. Taken together, BA may reduce the expression of PTHrP in MDA-MB-231 human metastatic breast cancer cells, RANKL/OPG ratio in PTHrP-stimulated human osteoblasts, and RANKL-induced osteoclastogenesis in bone marrow macrophages. BA may also prevent osteoporotic bone loss in OVX mice. Thus, BA can be beneficial agents for patients with secondary bone lesions associated with breast cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 34. doi:1538-7445.AM2012-34
Abstract 3400: A systems biology approach reveals common metastatic pathways in osteosarcoma
Authors: Flores Ricardo J. , Li Yiting , Vanucci Marina , Lau Ching C. , Man Tsz-Kwong , Lau Serrine S. 
Published: August 2012

Abstract
Background Osteosarcoma (OS) is the most common malignant bone tumor in children and adolescents. The survival rate of patients with metastatic disease remains very dismal. Nevertheless, metastasis is a complex process and a single-level analysis will not likely identify its key biological determinants. In this study, we used a systems biology approach to identify common metastatic pathways that are jointly supported by both mRNA and protein expression data in two distinct human metastatic OS models. Results mRNA expression microarray and N-linked glycoproteomic analyses were performed on two commonly used isogenic pairs of human metastatic OS cell lines, namely HOS/143B and SaOS-2/LM7. Pathway analysis of the up-regulated genes and glycoproteins separately revealed pathways associated to metastasis including RAS-related G-proteins signaling, cell cycle regulation, epithelial-to-mesenchymal-transition, cell adhesion, and WNT signaling. However, no common significant pathway was found between the two metastatic models, suggesting a very different biological nature of the cell lines. To address this issue, we used a topological significance analysis based on a “shortest path” algorithm to identify topological nodes that remained hidden from the independent transcriptomic and glycoproteomic analyses. Pathway analysis of the significant topological nodes revealed a striking concordance between the models and identified important common pathways, including “Cytoskeleton remodeling/TGF/WNT,” “Development/WNT signaling,” “Cytoskeleton remodeling/Cytoskeleton remodeling,” and “Cell adhesion/Chemokines and adhesion”. Of these, the “Cytoskeleton remodeling/TGF/WNT” was the top ranked common pathway from the topological analysis of the two cell line models. The up-regulation of proteins in the “Cytoskeleton remodeling/TGF/WNT” pathway in the SaOS-2/LM7 and HOS/143B models was further validated using a Reverse Phase Protein Array platform. Conclusions In this study, we used a systems biology approach by integrating genomic and proteomic data to identify key and common metastatic mechanisms in OS. The use of the topological analysis revealed hidden biological networks that are known to play critical roles in metastasis. Since WNT signaling has been previously implicated in OS and other tumors, further characterization of this common pathway and other topological pathways may lead to a novel therapeutic strategy for curing metastatic OS.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3400. doi:1538-7445.AM2012-3400