bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1477: Tumor cell-leukocyte fusion in human cancer: A melanoma brain metastasis with a donor-patient hybrid genome following allogeneic BMT
Authors: Lazova Rossitza , Laberge Greggory S. , Duvall Eric , Spoelstra Nicole , Sznol Mario , Cooper Dennis , Spritz Richard , Pawelek John M. 
Published: June 2012

Abstract
Tumor cell fusion with motile bone marrow-derived cells (BMDCs) has long been proposed as a mechanism for metastasis, but while such fusion has been demonstrated in animal models little is known of this in human cancer. Here we report the first genetic evidence for BMDC-tumor fusion and genomic hybridization in a human melanoma brain metastasis from a patient with a prior allogeneic bone marrow transplant (male-male, sibling). STR analyses of DNA from melanoma cells throughout the tumor revealed the presence of both donor and patient alleles, with common aberrant allelic patterns at multiple chromosomal loci indicating a clonal origin of the tumor. Methods. All procedures were in accordance with HIPAA regulations and approved by the Yale HIC. Donor and patient DNAs were obtained from frozen lymphocytes and from a patient buccal swab. Formalin-fixed, paraffin-embedded tumor specimens were stained by immuniohistochemistry with common leucocyte antigen (CLA) in order to avoid leucocytes during microdissection of tumor cells. LCA-negative tumor cells were isolated with an Arturus XT laser dissection microscope system. DNA was extracted and analyzed for donor and patient alleles using forensic STR analyses at 13 chromosomal loci and amelogenin for the X and Y. Tissue sections were analyzed from 14 areas throughout the tumor. Results. DNA from donor and patient lymphocytes showed balanced diploidy at all loci and the allelic patterns were consistent with the sibling relationship. On the other hand, DNA from tumor cells contained a mixture of donor and host alleles at some loci, only donor or patient alleles at others, and numerous allelic imbalances throughout–particularly for the X and Y (X:Y = 2.8:1) that pointed to a probable tumor genotype of XXXY. With few exceptions, aberrant genetic profiles seen in one tumor section were seen in all, demonstrating a clonal origin of the tumor. Conclusions. The results provide the first genetic proof of leucocyte-tumor fusion and genomic hybridization in human cancer and indicate that the tumor was generated from a single fusion event. While this report concerns only one case, we demonstrate that forensic genetic analyses of tumors arising as secondary malignancies represents a fruitful area for research in tumor cell fusion in human 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 1477. doi:10.1158/1538-7445.AM2011-1477
Abstract 148: Targeting DNA repair genes XRCC2 and XRCC4 with artificial miRNA sensitizes human brain tumor cells to radiation
Authors: Zheng Zhiming , Ng Wooi Loon , Wang Ya 
Published: June 2012

Abstract
Background: Previously, we reported that targeting DNA repair genes with miR-101 could sensitize human brain tumor cells to radiation (PLoS One 5: e11397, 2010). However, some tumor cell lines with high levels of endogenous miR-101 showed less response to exogenous miR-101 (our unpublished data). To overcome the resistance of the tumors to radiation, we designed artificial miRNAs to target XRCC2 (an important factor for homologous recombination repair (HRR)) and XRCC4 (an essential factor for non-homologous end-joining (NHEJ)) because both HRR and NHEJ are required for repairing radiation-induced DNA double strand breaks (DSBs) in mammalian cells and DNA DSBs are the severest threat to cell survival.
Methods: We constructed pLenti6/V5-GW/Em-GFP-miR lentiviral expression plasmids expressing artificial XRCC4 and XRCC2 miRNAs using Gateway Technology and chained artificial XRCC4 and XRCC2 miRNAs. To avoid triggering miRNA tailing and 3′-to-5′ trimming due to an extensive complementarity between a target RNA and an Argonaute1-bound miRNA, we mismatched 7 bases in the central bulge of the artificial miRNA. U87MG cells were transfected with the vector encoding both of the artificial miRNAs. XRCC4 and XRCC2 levels were measured by real-time PCR and Western blot. The effects of artificial miRNA on sensitizing U87MG cells to radiation were determined by clonogenic assay.
Results: The designed artificial XRCC4/XRCC2-miRNA could be over-expressed in U87MG cells and efficiently down-regulate the XRCC4 and XRCC2 levels. Most importantly, the artificial XRCC4/XRCC2-miRNA could efficiently sensitize the brain tumor cells to radiation.
Conclusion: The designed artificial miRNA targeting XRCC4 and XRCC2 could be a good tool to sensitize brain tumor cells to radiation, which provide a new approach for potentially improving radiotherapy.
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 148. doi:10.1158/1538-7445.AM2011-148
Abstract 1489: Function of Rho kinases on HCC tumor growth and metastasis
Authors: Wu Ying , Whalen Pamela M. , Wang Jean Yu , Li Gary , Pocalyko David , Wang Yuli 
Published: June 2012

Abstract
The Rho/ROCK (Rho-associated protein kinase) pathway has been found to be frequently upregulated in hepatocellular carcinoma (HCC). Clinico-pathological research has shown that increased RhoA and ROCK2 expression are associated with the presence of tumor microsatellite formation. RhoA is over expressed in 69% of HCC, and high RhoA levels are correlated with poor survival. ROCK2 protein level is upregulated in 54% of HCC, and its expression is associated with intrahepatic metastasis. The ROCK2 knockdown by short hairpin (sh)RNA leads to significant reduction of tumor formation. These observations suggest that Rho/ROCK pathway could be a potential therapeutic target for the treatment of liver cancer. Down-regulation of the Rho/ROCK pathway may inhibit tumor metastasis. However, the role of ROCK1 in HCC metastasis is still not clear. In order to dissect out the roles of ROCK1 and ROCK2 in liver tumor formation and metastasis, we used the shRNAmir- lentiviral system to knockdown ROCK1, ROCK2, and ROCK1/ROCK2 in HCC cell lines. The RNA and protein levels of ROCK1 and ROCK2 were significantly reduced in HCC cell lines that expressed shRNAs targeting ROCK1 and ROCK2. Orthotopically implanted HCC cells carrying shRNA targeted at ROCK1 and ROCK2 either alone or in combination were examined for tumor induction in mice. Our data showed that tumor growth was significantly reduced in those mice inoculated with cells expressing shRNAs. In addition, fewer tumor nodules as compared to the control (Non-target shRNA control) group were seen in those mice. Using qRT-PCR, we confirmed that the decreased ROCK activity was associated with the reduction of ROCK1 and ROCK2 RNA levels in mouse liver samples. Conclusion: our results indicate that both ROCK1 and ROCK2 are important for HCC tumor growth. Moreover, we demonstrated that ROCK1 played a more significant role than ROCK2 in HCC intrahepatic metastasis.
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 1489. doi:10.1158/1538-7445.AM2011-1489
Abstract 1495: Tyrosine phosphorylation of galectin-3 regulated its cleavage by PSA
Authors: Balan Vitaly , Nangia-Makker Pratima , Raz Avraham 
Published: June 2012

Abstract
Galectin-3, one of 15 animal lectins, is an intracellular and extracellular lectin which interacts with intracellular glycoproteins, cell surface molecules and extracellular matrix proteins. Recent research revealed that galectin-3 (gal-3) is involved in various biological phenomena including cell growth, adhesion, angiogenesis, apoptosis, motility and metastasis. This protein is widely expressed in various tumor cells and its expression is correlated with tumorigenesis, tumor progression and metastasis. The functions of gal-3 are dependent on its binding partners, its localization and can change as a result of post-translational modifications such as cleavage and phosphorylation. Recently we demonstrated that gal-3 can be phosphorylated by c-Abl at Tyr 79, 107 and 118; Tyr107 is the major phosphorylation site. In a recent report Saraswati et al revealed that gal-3 can be cleaved by prostate specific antigen after Tyr107. Our research confirms their data and demonstrates that phosphorylation of Tyr107 blocks this cleavage. This cleavage removes the collagen like sequence from carbohydrate binding domain of gal-3 and reduces the ability of gal-3 to create oligomers, thus blocking its ability to create lattice and promote cancer behavior of the cells. These results indicate an important role of post-translational modifications of galectin-3 in prostate 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 1495. doi:10.1158/1538-7445.AM2011-1495
Abstract 1497: Matrix metalloproteinase-9 mediates growth, invasion, and metastasis of human breast cancer cells
Authors: Mehner Christine , Miller Erin , Radisky Derek C. , Radisky Evette S. 
Published: June 2012

Abstract
Most breast cancer deaths are the consequence of metastasis from the primary site. In order to metastasize, tumor cells must escape the physical barriers that contain the growing primary tumor, enter the vascular system, exit the vascular system at a distant point, and colonize a distant organ. An important mediator of metastasis is matrix metalloproteinase-9, a member of the MMP family that has been found to be upregulated both in breast cancer cells and in the surrounding tumor stroma. Studies using animal models have sometimes produced apparently contradictory findings, due in part to methodology in which MMP-9 expression is suppressed throughout the host organism and throughout the course of tumor initiation and progression. To define the specific role of tumor cell-produced MMP-9 in metastasis of human breast cancer, we implemented a bioluminescent imaging animal model of metastasis in which luciferase-expressing MDA-MB-231 cells, infected either with control nontarget lentivirus (MDA-MB-231-NT) or with shRNA lentivirus targeting MMP-9 (MDA-MB-231-MMP9-KD), were orthotopically implanted into the mammary fat pads of immunocompromised mice. Tumor growth and development of lung metastases were assessed over 10 weeks using an IVIS imager. At 11 weeks mice were sacrificed, and tumor progression was assessed by ex vivo lung imaging and by immunohistochemical processing of the tumors and the lungs. Imaging studies revealed that primary tumors developing from MMP-9 knockdown cells grew more slowly throughout the course of the study (ranging from 25% to 50%), and that while the majority of the control group developed lung metastases, none of the mice injected with MDA-MB-231-MMP9-KD cells showed metastatic progression. After sacrifice, the measured tumor weight showed a median of 99 mg for the MDA-MB-231-MMP9-KD and 158 mg for the MDA-MB-231-NT tumors, showing that knockdown of MMP-9 inhibited tumor growth. Ex vivo imaging of the lungs confirmed the in vivo studies: no metastases were detected from MDA-MB-231-MMP9-KD cells, while all lungs of the MDA-MB-231-NT injected mice had detectable metastases (p=0.0079). Similarly, a single level immunohistochemical correlate found no metastases in the MDA-MB-231-MMP9-KD mice, while 3 of 4 mice with the non-target control cells showed large metastases (median 7×103 μm2). Our results demonstrate that expression of MMP-9 by human breast cancer cells plays a significant role in the progression of tumor growth and metastasis and provide insight into the potential of MMP-9 as a target for therapeutic intervention.
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 1497. doi:10.1158/1538-7445.AM2011-1497
Abstract 1499: MT1-MMP two-step activation in tumorigenesis
Authors: Golubkov Vladislav , Cieplak Piotr , Ratnikov Boris , Aleshin Alexander , Zhu Wenhong , Motamedchaboki Khatereh , Strongin Alex 
Published: June 2012

Abstract
Elevated activity of membrane type-1 matrix metalloproteinase (MT1-MMP) promotes cancer cell migration, invasion, and metastasis. MT1-MMP is synthesized as a zymogen, the latency of which is maintained by its prodomain. Excision by furin was considered sufficient for the prodomain release and MT1-MMP activation. We determined, however, that the full-length intact prodomain released by furin alone is a potent autoinhibitor of MT1-MMP. Additional MMP cleavages within the prodomain sequence are required to release the MT1-MMP enzyme activity. Using mutagenesis of the prodomain sequence and mass spectrometry analysis of the prodomain fragments, we demonstrated that the intracellular intradomain cleavage of the PGD-L50 site initiates the MT1-MMP activation (first step), whereas the 108RRKR111-Y112 cleavage by furin completes the removal and the degradation of the autoinhibitory prodomain and the liberation of the functional activity of the emerging enzyme of MT1-MMP (second step). Here we used the prodomain-based fluorescent biosensors to demonstrate that the proteolytic steps in MT1-MMP activation are differentially regulated in cancer cells versus normal cells. We determined that the intracellular cleavage of the PGD-L50 site represents an “on” and “off” mechanism that discriminates cancer cells from normal cells. To evaluate the significance of the PGD-L50 site cleavage in tumorigenic potential of MT1-MMP, the MCF7 cells transfected with the wild type MT1-MMP (MCF7-MT1) and the uncleavable L50D mutant (MCF7-L50D) were inoculated in the breast fat pads of nude mice. In 4 weeks palpable tumors were evident in all of the mice that received MCF7-MT1 and MCF7-L50D cells. The MCF7-L50D cells formed small tumors that reached ∼50 mm3 volume and remained unchanged from week 4 till week 10. On the contrary, the MCF7-MT1 tumors grew rapidly and reached ∼700 mm3 volume in 10 weeks. These data suggest that the intracellular cleavage of PGD-L50 site is critical for MT1-MMP two-step activation and tumorigenic activity. This intracellular cleavage does not occur in normal cells and the enzyme remained inhibited by it's non-covalently associated prodomain.
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 1499. doi:10.1158/1538-7445.AM2011-1499
Abstract 1502: Increased expression of KLK7 and KLK10 in papillary thyroid cancer
Authors: MacEwan Melanie , Mehta Vikas , Darr E. Ashley , Xie Suqing , Nowicki Theodore S. , Iacob Codrin , Suslina Nina , Reyes Ismael , Schantz Stimson , Shin Edward , Tiwari Raj , Geliebter Jan 
Published: June 2012

Abstract
The American Cancer Society estimates that there will be approximately 44,670 new cases of thyroid cancer and 1,690 deaths due to the disease in the United States in 2010. Approximately 80% of these cancers are papillary thyroid carcinoma (PTC), representing the most common endocrine malignancy. Kallikreins are serine proteases that have many physiological functions, including the remodeling of extracellular matrix (ECM). As PTC has the ability to degrade and remodel the ECM to facilitate penetration through the thyroid capsule and invasion of extra-thyroidal tissues, we investigated the expression of kallikrein 7 (KLK7) and kallikrein 10 (KLK10) in PTC. RNA expression of KLK7 and KLK10 in PTC was measured using real-time RT-PCR (normalized to GAPDH) (n = 26) and found to be significantly upregulated, with a mean fold change of 28.8 and 27.8 (P&lt;0.05), in the tumor samples, relative to matched, normal tissue. Immunohistochemical analysis for KLK7 and KLK10 on patient samples (n = 16) revealed significantly increased immunohistochemical scoring/expression, with a mean increase of 3.0 and 2.7 (scale of 1-4; p&lt; 0.001), respectively, in cancerous tissues, compared to adjacent, normal tissue on the same section. The data revealed a significant correlation between the expression of KLK7 and KLK10 on the both RNA level (Spearman r = 0.63, P&lt;0.01), and on the protein level (Spearman r = 0.687, p&lt;0.01). This coordinate expression suggests that the two kallikreins may share similar regulatory sequences. These data indicate that KLK7 and KLK10 may be useful biomarkers for the diagnosis of PTC in thyroid 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 1502. doi:10.1158/1538-7445.AM2011-1502
Abstract 1504: Characterization of the murine oral squamous cell carcinoma cell line AT84 stably overexpressing uPAR
Authors: Magnussen Synnove , Hanes Robert , Hadler-Olsen Elin , Uhlin-Hansen Lars , Svineng Gunbjorg 
Published: June 2012

Abstract
Cancers of the oral cavity are associated with poor prognosis, and almost half of the patients diagnosed with oral squamous cell carcinoma (SCC) will die from the disease. Compared to its counterpart in skin, one main differing feature is the ability of oral SCC to metastasize. A prerequisite for metastasis is the capability to invade the surrounding tissue and penetrate into the nearest blood- or lymphatic vessel. This initial step in metastasis requires several extracellular matrix degrading enzymes. One such enzyme is uPA (urokinase-type plasminogen activator), involved in pericellular proteolysis, where high levels are correlated with poor prognosis in several cancers. Upon binding of pro-uPA to its extracellular receptor uPAR, the enzyme is cleaved and activated. uPA further activates matrix metalloproteases (MMP's), also needed for matrix degradation. In addition, ample evidence shows that binding of uPA to uPAR triggers receptor-mediated cellular signaling. uPAR lacks a membrane spanning domain hence signal transduction has to be mediated through one or several membrane partners. uPARs role in the regulation of cell adhesion, migration and proliferation has been linked to its interplay with membrane partners such as integrins, EGFR, caveolin and G-protein coupled receptors (e.g. FPRL1). To better understand the role of uPAR in the invasive growth and metastasis of oral SCCs, the mouse oral SCC cell line, AT84 [1, 2], was stably transfected with uPAR. Overexpression of uPAR resulted in down regulation of epithelial marker E-cadherin and the cells display a more mesenchymal appearance, indicating epithelial-mesenchymal transition (EMT). In addition, elevation of uPAR expression increased migration in a wound healing assay. In contrast to previous reports, an increase in MMP-9 activity was not observed in these cells, although an increase in overall proteolytic activity could be found using gelatin as substrate. The cells were reintroduced into the C3H mouse to observe the role of uPAR in cancer progression in vivo. Results from the analysis of the host-tumor interactions within this syngenous mouse model will be presented.
1. Lou, E., et al., Clinical and pathological features of the murine AT-84 orthotopic model of oral cancer. Oral Dis, 2003. 9(6): p. 305-12.
2. Schultz-Hector, S. and S. Haghayegh, Beta-fibroblast growth factor expression in human and murine squamous cell carcinomas and its relationship to regional endothelial cell proliferation. Cancer Res, 1993. 53(6): p. 1444-9.
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 1504. doi:10.1158/1538-7445.AM2011-1504
Abstract 1506: Up-regulation of stromal matrilin-3 expression in advanced stage high-grade serous ovarian cancer
Authors: Yeung Zachary P. , Thompson Melissa S. , Yeung Tsz L. , Zaid Tarrik M. , Wong Kwong K. , Mok Samuel C. 
Published: June 2012

Abstract
Objective: Transcriptome profiling performed on RNA isolated from microdissected epithelial and stromal fibroblastic components of advanced stage high-grade serous ovarian cancer (HGSC) and normal ovarian epithelial tissue identified a set of genes coding for secretory proteins that were significantly up-regulated in ovarian cancer associated fibroblasts (CAFs). One of the most significant differentially expressed genes is matrilin-3 (MATN3), which has been shown to play an important role in cartilage morphogenesis. The purpose of this study is to validate the differential expression patterns of MATN3 and its role in ovarian cancer progression.
Methods: Validation studies on MATN3 expression were carried out using quantitative RT-PCR analysis on RNA samples isolated from the microdissected stromal and epithelial components of 44 HGSC samples and 10 normal ovaries. In addition, immunohistochemistry (IHC) was performed to determine over-expression of MATN3 in the stromal component of HGSCs. To assess the functional role of matrilin-3 in ovarian cancer pathogenesis, multiple ovarian cancer cells including SKOV3 ipluc, OVCA 432, OVCA 433, and ALST were treated with exogenous recombinant MATN3. Its effect on cell proliferation was evaluated by the WST-1 assay. Furthermore, the effect of MATN3 on invasion potential was determined by counting the number of cells migrating through a transwell membrane coated with a 0.1% type I collagen matrix containing 7.5 nM MATN3.
Results: Quantitative RT-PCR analysis showed significantly over-expression of MATN3 in the stromal component of HGSC compared to the epithelial component and the normal ovaries (P=0.003). Immunohistochemistry (IHC) confirmed overexpression of MATN3 in a majority of ovarian cancer stromal specimens. When treated with recombinant exogenous matrilin-3, ALST and SKOV3 ip luc ovarian cancer cells showed a dose-dependent inhibition of proliferation by MATN3. Treatment of ovarian cancer cells SKOV3 and OVCA 432 with exogenous MATN3 significantly decreased the number of cells migrating through the transwell membrane (P&lt;0.001).
Conclusions: Over-expression of MATN3 in ovarian cancer stroma inhibits cell proliferation and invasion potential. Further evaluating the underlying molecular mechanism of MATN3 in ovarian cancer progression is warranted.
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 1506. doi:10.1158/1538-7445.AM2011-1506