bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3392: Molecular determinants for the bone-metastatic potential of prostate cancer cells
Authors: Liu Qingxin , Jernigan Danielle , Fatatis Alessandro 
Published: August 2012

Abstract
Skeletal metastasis is the major cause of morbidity and death in patients with advanced prostate cancer (PCa). The propensity of cancer cells to progress into macroscopic lesions at secondary sites relies on the successful adaptation of Disseminated Tumor Cells (DTCs) to the new microenvironment. This requirement explains the predilection of most tumors to produce clinical metastases in selected organs although they can seed malignant cells also in several other tissues. It seems plausible that the metastatic fate of DTCs is dictated by the pleiotropic effects of specific genes and their encoded products establishing functional interactions with the surrounding stroma. The main objective of this study was to identify these molecular mediators of cell survival and growth in the bone with the ultimate goal of identifying effective therapeutic targets to counteract PCa metastases. Using a pre-clinical animal model of experimental metastasis, we have recently shown that exogenous over-expression of PDGFRα in non-metastatic prostate phenotypes conferred bone-metastatic potential and a monoclonal antibody targeting the receptor reduced bone metastatic tumors by more than 70%. Here we report that comparative gene-expression analyses conducted with PCa cells showing different intrinsic metastatic potential, as well as prostate phenotypes that fail to increase their metastatic behavior upon PDGFRα expression, resulted in a bone-metastatic gene signature including three genes encoding for soluble, secreted proteins. This suggests that DTCs with aggressive metastatic behavior modify the bone microenvironment in their favor, not only coercing the stroma to support their own survival, but also allowing other malignant phenotypes, that would otherwise fail to thrive, to grow into macroscopic tumors. We are currently testing this cell-cooperation in metastasis as well as functionally validating our three-gene signature by stably silencing or over-expressing each of the three newly identified genes in bone-metastatic and non-metastatic PCa cells, respectively.
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 3392. doi:1538-7445.AM2012-3392
Abstract 3399: Detection of rare mutations in plasma by droplet digital PCR
Authors: So Austin , Hindson Benjamin , Koehler Ryan , Saxonov Serge , Karlin-Neumann George , Ericson Nolan , Bielas Jason 
Published: August 2012

Abstract
Detection and quantitation of specific mutations in circulating plasma holds promise for earlier and less invasive diagnosis of disease. This presents significant analytical challenges, particularly as the biomarker may differ from its highly abundant wildtype by only a single nucleotide. Conventional methods have poor selectivity and fail to detect mutant sequence below 1 in 100 wildtype sequences. Compounding this, the amount of circulating nucleic acid in plasma is low. Here we present a simple strategy using droplet digital™ PCR (ddPCR™) for the detection of somatic mutations with high selectivity and sensitivity. Based on the simple principle of sample partitioning into water-in-oil microdroplets, this ddPCR method increases the abundance of a mutant DNA sequence up to 20,000 times compared to an equivalent bulk PCR reaction. Using conventional TaqMan chemistries and workflow, selectivities of up to 1/100,000 can readily be achieved in any laboratory. We evaluated ddPCR for the detection and quantitation of several clinically important mutations in the EGFR and KRAS loci from clinical samples derived from normal and tumor plasma samples. We also demonstrate the feasibility of multiplexing of Kras and EGFR assays to improve sample processing efficiency.
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 3399. doi:1538-7445.AM2012-3399
Abstract 3401: Amplification of the STOML3, FREM2, and LHFP genes is associated with mesenchymal differentiation in gliosarcoma
Authors: Nagaishi Masaya , Kim Young-Ho , Mittelbronn Michel , Giangaspero Felice , Paulus Werner , Vital Anne , Nakazato Yoichi , Lachuer Joël , Ohgaki Hiroko 
Published: August 2012

Abstract
Gliosarcoma is a rare glioblastoma variant characterized by a biphasic tissue pattern with alternating areas displaying glial (GFAP-positive) or mesenchymal (reticulin-positive) differentiation. Previous analyses showed identical genetic alterations in both glial and mesenchymal tumor areas, suggesting that gliosarcomas are genetically monoclonal, and mesenchymal differentiation was considered to reflect the elevated genomic instability of glioblastomas. In the present study, we compared genome-wide chromosomal imbalances using array CGH (105K) in glial and mesenchymal tumor areas of 13 gliosarcomas. Patterns of gain and loss were similar, except for gain at 13q13.3-q14.1 (log2 ratio ≤ 3), containing the STOML3, FREM2, and LHFP genes, which was restricted to the mesenchymal tumor area of a gliosarcoma. Further analyses of 64 cases of gliosarcoma using quantitative PCR showed amplification of the STOML3, FREM2 and LHFP genes in 14 (21%), 10 (15%), and 7 (11%) of mesenchymal tumor areas but not in glial tumor areas. Immunohistochemistry confirmed that STOML3 and FREM2 overexpression was more extensive in mesenchymal than in glial tumor areas. These results suggest that mesenchymal components in a small fraction of gliosarcomas may be derived from glial cells with additional genetic alterations.
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 3401. doi:1538-7445.AM2012-3401
Abstract 3406: Impact of TJP-1 and TWIST expression on post-operative prognosis in hepatocellular carcinoma
Authors: Nagai Tomoyuki , Arao Tokuzo , Matsumoto Kazuko , Sakai Kazuko , Kudo Kanae , Kaneda Hiroyasu , Tamura Daisuke , Aomatsu Keiichi , Kimura Hideharu , Fujita Yoshihiko , Hagiwara Satoru , Sakurai Toshiharu , Ueshima Kazuomi , Haji Seiji , Kudo Masatoshi , Nishio Kazuto 
Published: August 2012

Abstract
Epithelial-Mesenchymal transition (EMT) plays a critical role in cancer progression and metastasis. However, whether the overexpression of EMT-related genes mediates the malignant phenotype in HCC remains largely unclear. In this study, we examined the relationship between mRNA expression levels of EMT-related genesand 12 clinical characteristics including recurrence-free survival and overall survival in HCC patients who had undergone curative hepatic resection. The mRNA expression levels of 15 genes (CDH1, CDH2, Snail, Slug, ZEB1, ZEB2, TWIST, Vimentin, Fibronectin, DDR2, S100A4, TJP-1/ZO-1, FOXC2, SIX1, GSC) was determined by quantitative real-time PCR in tissues from 72 HCC tumors. Twist expression was significantly upregulated in recurrence group (p=0.02). The upregulation of Twist and the downregulation of TJP1 were significantly related with poor prognosis in univariate and multivariate analysis. In conclusion, Twist and TJP1 may be predictive biomarkers in patients with HCC after hepatectomy. Our findings provide a novel insight into TJP1 and HCC, warranting further investigations.
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 3406. doi:1538-7445.AM2012-3406
Abstract 3407: Analysis of the MET dependent proteins expression in cervical carcinoma cell lines
Authors: Trzyna Elzbieta 
Published: August 2012

Abstract
MET receptor and its ligand, hepatocyte growth factor (HGF) are important players in mitogenesis, morphogenesis and acquisition of migratory phenotype. HGF/MET axis plays its role in neoplastic transformation through activation of key oncogenic pathways and influencing dissociation ability of cells leading to metastasis. Overexpression of MET receptor has been observed in a variety of tumors. Cervical carcinoma (CC) is the second most common malignancy in women worldwide, and it remains a leading cause of cancer-related death for women in developing countries. Clinical manifestation of CC is very diverse from in situ cancers to very invasive and strongly metastatic to neighbouring and distal organs (lungs, liver, bones). In this work we study the expression of MET dependent proteins in cervical carcinoma cell lines (HeLa, HTB34, HTB35) using mass spectrometry analysis. We prepared cervical carcinoma cell lines with silenced MET gene. Cells were transduced with lentiviral vector containing shRNA against MET. shRNA was designed based on siRNA sequence silencing this particular gene in 80%. Silenced and wild type cells were cultured and lysed. Proteins from various cell compartments were isolated. 2-dimentional electophoresis and silver staining of the gels were performed followed by software and mass spectrometry analysis. We detected differences in proteins expression among wild type samples and silenced HTB34 cell line in amount of proteins (examples: Heat shock protein 75 kDa, Leukocyte elastase inhibitor). Analysed proteins were also separated by 2D electrophoresis and we observed differences in pH of these proteins among wild type and silenced probes (examples: TAR DNA-binding protein 43, Succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial, Leukotriene A-4 hydrolase). Other proteins were present either in wild type HTB34 (example: Importin subunit alpha-2, Putative elongation factor1-alpha-like3,) or silenced HTB34 (example: Serine/threonine-protein phosphatase PP1-alpha catalytic subunit, Serine/threonine-protein phosphatase PP1-beta catalytic subunit, LIM and SH3 domain protein 1). Analysis of these proteins gives as information about particular proteins involved in MET dependent regulation of cervical carcinoma cell lines. Characterization of HTB35 and HeLa proteins is pending. The results of this study can be used to better understand the biology of cervical carcinoma. They can be also used to develop new therapeutic strategies to treat cervical carcinoma 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 3407. doi:1538-7445.AM2012-3407
Abstract 3428: Genome-stabilizing functions of NM23 in metastatic melanoma
Authors: Jarrett Stuart G. , Novak Marian , Merlino Glenn , Slominski Andrzej , Kaetzel David M. 
Published: August 2012

Abstract
The metastasis suppressor protein NM23-H1 exhibits two enzymatic activities in vitro with potential roles in the maintenance of genomic integrity: a nucleoside diphosphate kinase (NDPK) activity that maintains balance in nucleotide pools and a 3′-5′ exonuclease (3′-5′ EXO) activity that could provide proofreading during DNA repair and replication. Studies were conducted in cell culture and in vivo to determine the extent to which NM23-H1 expression contributes to maintenance of genomic integrity, as well as suppression of melanoma initiation and progression. Expression of NM23-H1, and possibly NM23-H2, was shown to be necessary for timely repair of UVR-induced (6-4) photoproducts (6-4PP) in melanoma cell lines, as well as in transgenic mouse-derived melanocytes and embryo fibroblasts, as determined by immunoslot-blot assay. NM23 protein expression also suppressed the incidence of both spontaneous and UVR-induced mutations as determined using the 6-thioguanine resistance colony-forming assay. Point mutations that either selectively or tandemly disrupted the NDPK and 3′-5′ EXO activities of NM23-H1 exhibited compromised DNA repair and mutation-suppressing activities, consistent with contributions of both enzymatic functions. UVR induced rapid (&lt; 5 min) translocation of NM23-H1 to the nucleus, where it colocalized closely in concert with 6-4PPs, strongly suggesting direct participation in the repair of those lesions. Consistent with this proposed function, transgenic mice engineered to be hemizygous-null in expression of both NM23-M1 and NM23-M2 (the mouse homologs of NM23-H1 and NM23-H2, respectively) were rendered susceptible to UVR-induced melanoma and epithelioid follicular cyst formation. Moreover, this NM23-deficient genotype conferred an aggressively metastatic phenotype to the HGF-expressing transgenic mouse model of UVR-inducible melanoma. Metastasis of highly-pigmented cells to draining lymph nodes and the lungs was seen in most cases, with lesions also occasionally seen in liver, brain and bone. Taken together, these results demonstrate a critical role for NM23 proteins in DNA repair and suppressing mutations under basal and genotoxic conditions. Importantly, they highlight for the first time a tumor suppressor function in the context of UVR-induced melanoma in vivo, and suggest a novel metastasis suppressor activity through suppression of metastasis-driving mutations.
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 3428. doi:1538-7445.AM2012-3428
Abstract 3429: AKAP12/SSeCKS inhibits peritoneal metastasis by regulating chemokine production
Authors: Akakura Shin , Muramatsu Masashi , Ko Hyun Kyung , Gelman Irwin H. 
Published: August 2012

Abstract
AKAP12/SSeCKS/Gravin (AKAP12) is thought to act as a metastasis suppressor through its direct scaffolding of major signaling proteins such as PKC, PKA and Src, in a spatiotemporal manner (1). For example, AKAP12 inhibition of Src-mediated oncogenic signaling, including induction of VEGF secretion by tumor cells, correlates with inhibition of neovascularization at metastatic sites (2). We have established AKAP12-null (KO) mice and demonstrated that they are cancer-prone in regards to the formation of spontaneous prostatic dysplasia and to carcinogen-induced skin cancer formation (3, 4). However, the role of AKAP12 in host microenvironment in regards to tumor or metastasis control has yet to be elucidated. In this study, we utilized an orthotropic, subcutaneous injection model of B16F10 melanoma to address whether the loss of AKAP12 in the host facilitates metastasis. Although the size of the primary tumors was similar in WT vs. KO mice, KO mice exhibited increased rates of peritoneal metastasis. The peritoneal fluid (PF) of KO mice was more potent than WT-PF in inducing in vitro chemotaxis. Comparison of the cytokines/chemokines using antibody arrays showed a severe upregulation of multiple potential chemoattractants in the KO-PF, including CXCL9/10/11, known ligands for CXCR3, a chemokine receptor upregulated 12-fold in B16F10 versus the low-metastatic B16F0 variant. Pre-injection of KO-PF, but not WT-PF, into WT mice was sufficient to induce high levels of peritoneal metastasis from subcutaneous sites. Taken together, our study suggests that AKAP12 controls metastasis by regulating the production of chemoattractants in the peritoneum, produced either by local microenvironmental cells or by recruited inflammatory cells. References: (1) Gelman, I. H. (2002) Front Biosci 7, 1782-1797. (2) Su, B., Zheng, Q., Vaughan, M.M., Bu, Y., and Gelman, I.H. (2006) Cancer Res. 66, 5599-5607 (3) Akakura, S., Huang, C., Nelson, P. J., Foster, B., and Gelman, I. H. (2008) Cancer Res. 68, 5096-5103. (4) Akakura, S., Bouchard, R., Bshara, W., Morrison, C., and Gelman, I. H. (2011) Int. J. Can. 129, 2025-2031.
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 3429. doi:1538-7445.AM2012-3429
Abstract 3430: Role of Tip60 in human melanoma cell migration, melanoma metastasis and patient survival
Authors: Chen Guangdi , Cheng Yabin , Zhang Zhizhong , Martinka Magdalena , Li Gang 
Published: August 2012

Abstract
The tumor suppressor Tip60 plays a major role in transcription, DNA damage response, apoptosis and cancer development, but its role in melanoma is unknown. In this study, we investigated the role of Tip60 in melanoma pathogenesis and assessed its prognostic value. Using tissue microarrays consisting of 448 cases of melanomas (201 for the training set and 247 for the validation set) and 105 cases of nevi, we found that Tip60 expression was significantly reduced in metastatic melanoma compared to normal nevi (P = 0.045), dysplastic nevi (P = 0.047) and primary melanoma (P = 0.001). Kaplan-Meier survival curve and univariate Cox regression analyses showed that reduced Tip60 expression was associated with a poorer five-year disease-specific survival in primary melanoma (P = 0.016) and metastatic melanoma patients (P = 0.027). Multivariate Cox regression analyses indicated that Tip60 expression was an independent prognostic marker for primary (P = 0.002) and metastatic melanomas (P = 0.035). In vitro wound healing assay showed that enforced Tip60 expression inhibited melanoma cell migration suggesting that Tip60 might regulate melanoma metastasis. Finally, we showed that overexpression of Tip60 in melanoma cells resulted in significantly increased chemosensitivity. Our data indicate that Tip60 may serve as a potential biomarker for melanoma patient outcome as well as a potential therapeutic target.
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 3430. doi:1538-7445.AM2012-3430
Abstract 3435: NM23-H1 suppresses melanoma cell motility by promoting strong adhesions between fibronectin and α4α1 integrin
Authors: Novak Marian , Yang Xiuwei H. , Jarrett Stuart G. , Kaetzel David M. 
Published: August 2012

Abstract
The metastasis suppressor NM23-H1 has a prominent role in melanoma and other leading malignancies, where loss of NM23-H1 expression is associated with onset of aggressive phenotypes and metastasis. NM23-H1 blocks multiple facets of the metastatic cascade, with autonomous cell motility being perhaps the most scrutinized across multiple cancer types. However, the molecular mechanisms through which NM23-H1 suppresses cellular motility in melanoma are poorly understood. Herein, we report a novel mechanism of motility suppression by NM23-H1 in melanoma via upregulation of the extracellular matrix (ECM) component fibronectin. In agreement with previous reports, forced expression of NM23-H1 in metastatic melanoma cell lines 1205LU and MDA-MB-435s/M14 led to a significant decrease in random cell motility. The resultant sedentary phenotype was associated with pronounced changes in cell morphology, including a highly flattened appearance and marked increases in actin stress fiber formation and the size of focal adhesions. In light of the known roles of cell adhesion in conveying such phenotypic changes, we measured the effect of NM23-H1 on expression and localization of fibronectin, a major component of focal adhesion complexes. Forced expression of NM23-H1 resulted in significantly increased expression of endogenous fibronectin protein, which was concentrated at focal adhesion sites. To assess the contribution of NM23-induced expression of fibronectin to formation of immobilizing adhesions, blocking antibodies directed against α4α1 and Δ5α1 integrins, the dominant fibronectin receptors on melanoma cells, were applied. Antibodies directed against integrin α4, but not Δ5, reversed the suppressing effect of forced NM23-H1 expression on cellular motility. These findings indicate a novel role of NM-23-H1 in regulating endogenous fibronectin-mediated cell movement, a critical aspect of melanoma metastasis.
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 3435. doi:1538-7445.AM2012-3435
Abstract 3437: A natural plant product to inhibit breast cancer metastasis
Authors: Kundu Namita , Ma Xinrong , Goloubeva Olga , Holt Dawn , Kochel Tyler , Fulton Amy M. 
Published: August 2012

Abstract
In the United States, breast cancer death is the second leading cause of cancer deaths in women, primarily due to the occurrence of metastatic disease. We have identified a potential novel therapeutic agent derived from an edible root of the plant Colocasia esculenta, commonly known as taro, which has significant antimetastatic activity in a preclinical model of metastatic breast cancer and that should have minimal toxicity. We have shown for the first time that a water-soluble extract of taro (TE) potently inhibits lung colonizing ability (95-99%) as well as spontaneous metastasis from mammary gland-implanted tumors (85%), in a murine model of highly metastatic ER, PR and Her-2/neu negative breast cancer. TE modestly inhibits the proliferation of some, but not all, breast and prostate cancer cell lines and also causes morphologic changes including cell rounding. TE inhibits prostaglandin E2 (PGE2) levels and because PGE2 is a potent immune modulator, we examined the role of immunity in the therapeutic response to TE. We first examined the effect of TE on Natural Killer (NK) cell activities. TE modestly increases NK-mediated tumor cell lysis in vitro. We determined the effect of NK depletion on TE efficacy in vivo. The ability of TE to inhibit metastasis was modestly compromised in NK-depleted mice indicating that NK cells play a minor role in TE-mediated antimetastatic activity. To examine the role of T and B lymphocytes, TE efficacy was examined in Balb/c SCID mice. Antimetastatic activity of TE was completely lost in SCID mice lacking mature T and B cells. Thus, T and /or B cell functions contribute to the mechanism by which TE inhibits metastasis. In published studies we have identified the active component of TE as one of three closely related taro proteins, tarin, taro lectin and 12-kDa storage protein. Current studies are determining how these candidate proteins affect immune functions to inhibit breast cancer metastasis.
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 3437. doi:1538-7445.AM2012-3437