bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5215: Detection of circulating tumor cells in peripheral blood of patients with renal cell carcinoma
Authors: Goebel Steffen , Bluemke Karen , Bilkenroth Udo , Meye Axel , Fuessel Susanne , Lautenschlaeger Christine , Melchior Andres , Heynemann Hans , Fornara Paolo , Taubert Helge 
Published: June 2012

Abstract
Detection of circulating tumor cells in peripheral blood of patients with renal cell carcinoma
The aim of this study was to evaluate the clinical relevance of the presence of disseminated tumor cells in peripheral blood, so called circulating tumor cells (CTCs), for renal cell carcinoma (RCC) patients. 233 peripheral blood samples from 154 RCC patients were investigated for the presence of disseminated tumor cells (DTCs) by autoMACS technique and immunocytochemical (ICC) staining of cytokeratin. The frequency of CTCs was analyzed statistically for correlation with relevant clinical data.
Two kinds of tumor cells were detected: those with expression of cytokeratin 8/18 (CK+), but also cells without a detectable CK+ expression, which we called large blue stained (Bl+) cells with a tumor-like morphology. After following the CD45 autoMACS depletion protocol, we identified CTCs in 96 out of 233 peripheral blood samples (41%), which originated from 81 out of 154 (53%) RCC patients. A significant correlation between the detection of CTCs and positive lymph node status (p &lt; 0.001; Chi-square test) and the presence of synchronous metastases at the time of primary tumor resection (p &lt; 0.02; Chi-square test) was found. In a multivariate Cox's regression hazard model, presence of CK+ CTCs was significantly correlated with poor overall survival for RCC patients (RR=2.3; p &lt; 0.05).
The presence of CTCs correlated to lymph node status and presence of synchronous metastases in RCC. It is important to evaluate CK+ and Bl+ tumor cells together to determine the role of CTCs in tumor behavior and disease progression. Detection of CK+ CTCs in peripheral blood is a significant and independent prognostic factor for RCC.
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 5215. doi:10.1158/1538-7445.AM2011-5215
Abstract 5220: Increased expression of formyl peptide receptor (FPR) and formyl peptide receptor like-1 (FPRL1) correlates with high-risk clinical/histologic features in melanoma
Authors: Chakravarti Nitin , Peddareddigari Vijay G. R. , Warneke Carla L. , Johsnon Marcella M. , Hwu Patrick , Prieto Victor G. 
Published: June 2012

Abstract
Melanoma is an aggressive malignancy with a relatively high metastatic rate, responsible for almost 60% of lethal skin tumors. Despite numerous efforts, there is still a need to better understand the molecular pathways involved in malignant melanoma metastasis. FPR and its variant FPRL1, which belong to the GPCR family, have been shown to be involved in metastasis of glioma and ovarian tumor cells via activation of various signaling cascades. It is unknown whether expression of these receptors contributes to the pathogenesis of melanoma. In order to test the hypothesis that aberrant expression of these GPCRs plays a significant role in melanoma progression, we have performed semiquantitative immunohistochemical analysis of FPR and FPRL1 in benign nevi (n=49), primary melanomas with and without metastasis (n=130), and melanoma metastases (n=47 cases). A significant positive correlation was observed between the percentage of positive cells and staining intensity for FPR (p=0.001) and FPRL1 (p=0.009) with progression from benign nevi to primary melanoma. Significantly higher levels of FPR were observed in those lesions having higher Breslow thickness (p=0.044) and ulceration (p=0.019), which are well-established markers of poor clinical outcomes in patients with cutaneous melanoma. On the other hand, lesions showing a radial growth pattern expressed low levels of FPR (p=0.027). A gain in FPRL1 staining was seen in lesions displaying microscopic satellitosis (p=0.051). Disease-specific survival was significantly shorter in patients with increased cytoplasmic expression of FPR (log rank test, p=0.022). Thus, overexpression of FPR and FPRL1 correlates with disease progression and high-risk clinical and histologic features in melanoma. In addition, FPR expression is associated with shorter disease-free survival. Therefore, these markers may be an important therapeutic target in patients with melanoma.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5220. doi:10.1158/1538-7445.AM2011-5220
Abstract 5232: Lymphovascular breast carcinoma tumoral emboli beget emboli through stem-cell initiated self-budding histogenesis
Authors: Barsky Sanford H. , Ye Yin , Tellez Joseph D. , Belcher Meagan 
Published: June 2012

Abstract
Previous studies in our laboratory have indicated that the lymphovascular embolus is not simply a cellular fragment that detaches from the main tumor passively but represents an active clonal selection for a stem cell phenotype exhibiting enhanced stem cell signaling and survival pathways. Lymphovascular emboli exhibit increased resistance to chemotherapy and patients with large numbers of lymphovascular emboli exhibit decreased disease-free survival and poorer prognosis. Florid lymphovascular emboli is the diagnostic signature of inflammatory breast cancer (IBC) and other aggressive metastasizing cancers. The emboli have been presumed to form as a result of lymphovascular invasion but this event is thought to be rare and therefore would not alone explain the large number of emboli observed in IBC and other highly metastatic carcinomas. The reasons why some patients exhibit large numbers of lymphovascular emboli whereas other patients exhibit only rare numbers remain unknown. We wanted to specifically address this question and thus carried out both animal and in vitro imaging studies with our human xenograft model of inflammatory breast cancer, MARY-X, which exhibits florid emboli in mice and gives rise to high density spheroids in vitro. We also carried out morphometric studies on the density of human lymphovascular emboli in 25 IBC and 250 non-IBC cases and subsequent laser capture microdissection. Animal and in vitro multicolor imaging studies using anti-E-cadherin and anti-podoplanin showed evidence of self-budding histogenesis within the lymphovascular spaces with one parent embolus giving rise to daughter emboli. Correspondingly, budding spheroidgenesis was observed in vitro. Density studies of tumoral emboli in the human cases showed their numbers distributed over an exponential rather than linear range. By both RT-PCR and IHC, emboli compared to their non-embolic invasive carcinoma areas exhibited five-ten fold higher stem cell markers including Stellar, H19, Rex-1, Nestin, CD133 and Aldehyde Dehydrogenase 1 (ALDH1) as well as stem cell transcriptional determinants including OCT4, SOX2 and Nanog, and stem cell signaling pathways, eg., Bmi-1, Hedgehog and Notch3. These studies, while not explaining the genesis of the initial embolus, show conclusively that emboli beget emboli through stem-cell initiated self-budding histogenesis. It is this later process which is the more important one because it accounts for the exponential numbers of emboli seen in the human cases which exhibit aggressive behavior.
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 5232. doi:10.1158/1538-7445.AM2011-5232
Abstract 5246: Genomic determinants of aggressive phenotype in oral SCC
Authors: Sibson David R. , Lloyd Bryony , Woolgar Julia , Risk Janet , Shaw Richard , Dhanda Jag 
Published: June 2012

Abstract
Background: Oral squamous cell carcinoma (OSCC), the common form of HNSCC, affects over 600,000 cases worldwide per annum. We reviewed 561 consecutive cases in Liverpool1 finding that the most predictive marker for death was extra-capsular spread (ECS) from cervical lymph nodes (p&lt;0.001). Overall survival at 5 years was 56% for all 561 cases, but only 24% in the ECS group independently of its site, extent or the stage of the primary tumour2. The presence of ECS predicted for recurrence, usually at the primary site, even when surgical margins were generous indicating that this aggressive phenotype is likely to be expressed in the primary tumour as much as in the metastatic cells.
Hypothesis: We hypothesised that molecular pathways represented by global gene expression signatures would be detected in the samples associated with ECS.
Methods: High density exon array expression analysis was performed on fresh frozen samples comprising T2 and T4 stage OSCC cases having no nodal involvement; positive nodes without ECS or positive nodes plus ECS picked longitudinally from a single centre series (n&gt;200) with bias towards increasing the numbers with ECS. Contingency tests were performed to assess the significance of ECS associated pathways.
Results and Discussion: Power analysis showed that 90% of all ≥ twofold differences in gene expression between node negative & ECS cases were significant. Affected pathways included: keratinocyte differentiation, ECM remodelling, chemokines & adhesion, TGF & WNT: cytoskeletal remodelling, regulation of actin cytoskeleton by rho GTPases & cell adhesion/ histamine H1 receptor signalling/loss of cell barrier (p values:7.7×10−15 – 1.9×10−6).
A 29 gene signature able to discriminate the ECS from the non-ECS cases with 78% sensitivity and 86% specificity was found. Blocked differentiation of keratinocytes at an early (“stem cell”/ EMT) stage was suggested by the genes which included keratin 15, keratinocyte differentiation-associated protein, retinol binding protein 1, cellular serine peptidase inhibitor (Kazal type 6), and stratifin implicated in mesenchymal stem cells, basal, suprabasal expression and keratinocyte activation and differentiation. The signature may be connected with these tumours having poor prognosis.
Conclusion: This is a significant and novel finding suggesting that the pattern of metastasis in regional lymph nodes can be predicted by molecular pathways prevalent in a small oral biopsy.
1. Rogers et al. Oral Oncol 2009;45(3):201-211
2. Shaw et.al. Head Neck 2010;32(6):714-722
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 5246. doi:10.1158/1538-7445.AM2011-5246
Abstract 5257: Expression and functional role of CXCR5 and CXCL13 in non-small cell lung carcinoma (NSCLC)
Authors: Singh Rajesh , Singh Shailesh , Grizzle William E. , Lillard James W. 
Published: June 2012

Abstract
Lung cancer is the leading cause of cancer related deaths worldwide. Chemokines and their corresponding receptor have been shown to play important role in cancer progression including lung cancer. In this regard, chemokine receptor CXCR5 has been implicated in metastatic dissemination in different models of melanoma, breast and prostate cancer. In this study we have shown that CXCR5 is highly expressed by the lung cancer cell lines and non-small cell lung carcinomas (NSCLC) tissue. CXCL13, which is the only natural ligand for CXCR5 is also expressed within the tumor. Retrospective analysis of CXCR5 expression in 45 patients specimens showed significantly higher expression of CXCR5 in Squamous cell carcinoma and Adenocarcinoma. Interestingly, nuclei of tumor cells were also positive for CXCR5 in more than 50% cases. Furthermore, serum analysis showed significantly higher serum levels of soluble CXCL13 in patients with Adenocarcinoma and Squamous cell carcinoma (n=31) compared to normal controls (n=9). The mechanism underlying these clinically and biologically important finding need to be further explored. Increased serum CXCL13 in lung cancer patients with metastatic disease required further validation as a potential therapeutic target and/or diagnostic marker for lung 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 5257. doi:10.1158/1538-7445.AM2011-5257
Abstract 5262: The role of Bcl-2 in colon cancer metastatic progression
Authors: Wang Wang , Are Chandrakanth , Brattain Michael G. 
Published: June 2012

Abstract
Colon cancer is the second most lethal malignancy in the United States. The majority of deaths are related to metastasis, for which no effective therapies are currently available. While much is known about oncogenic initiation of colon cancer, the mechanisms by which cancer cells survive and metastasize in spite of the cellular stresses associated with this process require further investigation. Recent studies indicated that deregulation of apoptosis contributes to metastasis, and deregulation of Bcl-2 family members, which control the mitochondrial-dependent apoptosis pathway, is correlated with cancer progression.
We have initiated these studies using a unique othotopic implant model based on closely related colon cancer cell lines. HCT116 and HCT116b cells were isolated from the same primary colon tumor and both bear the H1047R PIK3CA mutation and form progressively growing invasive orthotopic primary tumors. However, only HCT116 cells exhibit metastatic potential. Interestingly, we found that Bcl-2 is highly expressed in HCT116 cells, but not in HCT116b cells. Overexpression of exogenous Bcl-2 in HCT116b cells, and complementary studies by shRNA mediated stable knockdown and overexpression of dominant negative forms of Bcl-2 molecule in metastatic HCT116 cells indicated that Bcl-2 is essential for their ability to withstand external stress. Current studies in our orthotopic model demonstrated that HCT116b tumors bearing exogenous Bcl-2 associated with increased cell survival and reduced center necrosis. Future study will determine whether this significant alteration in the expression of Bcl-2 associates with the distal metastatic capability of colon 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 5262. doi:10.1158/1538-7445.AM2011-5262
Abstract 5268: CXCR4 and P-glycoprotein N-glycan patterning in developing cancer cells
Authors: Ivey Stan , Shan Yufei , Owens Tori A. 
Published: June 2012

Abstract
Human CXCR4 and P-glycoprotein (Pgp) are N-glycosylated membrane proteins overexpressed in cancer cells. CXCR4 is thought to be an initiator of neuroblastoma metastasis to bone tissue and is overexpressed in neuroblastomas. Pgp is a heavily glycosylated, ATP-dependent drug efflux pump overexpressed in uterine sarcomas. Pgp is responsible for multidrug resistance in some tumors. Our lab is studying the N-glycan profiles of CXCR4 and Pgp in neuroblastoma (IMR-32) and uterine sarcoma cells (MES-SA and MES-SA/Dx5). We believe CXCR4 and Pgp are closely involved in metastasis. To better understand the molecular mechanisms of the metastatic roles of CXCR4 and Pgp, we are characterizing their respective complements of N-glycans. CXCR4 contains a N-linked oligosaccharide on two separate extracellular loops; moreover, Pgp has 3 N-glycans present on a 9 amino acid stretch near its N-terminus. We believe both protein N-glycan moieties are differentially glycosylated enough to act as markers for identifying and staging cancer cells. Our previous studies have shown that Pgp overexpressed in MES-SA/Dx5 cells contains at least two different complex N-glycans; a high mannose tree and a hybrid, sialic acid-capped oligosaccharide. To build on our previous studies, we have developed a novel approach to further characterize CXCR4 and Pgp N-glycans using polyclonal antibodies (pAbs) raised to the specific amino acid sequences containing the sugars in both cancer proteins. We are using these inimitable pAbs to aid in the isolation, sequencing, and profiling of specific N-glycan changes that are associated with the stage of each of the cancer cell lines mentioned above. Our pAb panels bind the native, expressed glycoforms of CXCR4 and Pgp in cells and on Western blots. We are using pAb affinity columns to capture protease-released glycopeptides. Once captured, we intend to sequence each of the released glycopeptides’ oligosaccharides to verify their saccharide sequences in the different cancer cell stages. Furthermore, we predict that the resultant glycopeptide gel and blot patterns will ‘bar code’ the specific cancer stage of the cells lines studied. We envision that these glycopeptide patterns can be used to identify and catalog the various stages of developing cancer cells.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5268. doi:10.1158/1538-7445.AM2011-5268
Abstract 5269: Mechanistic insights into regulation of metastasis by Sipa1
Authors: Geiger Thomas R. , Mattaini Katie , Williams Mia , Walker Renard , Alsarraj Jude , Borges Rosan Nieves , Hunter Kent 
Published: June 2012

Abstract
Metastasis is the major cause for morbidity and mortality of cancer patients. Still, the molecular mechanisms underlying metastasis are incompletely understood. Conceivably, a better knowledge of the metastatic process will enable the design of better treatments for cancer patients in the future.
Previously, we have shown that genetic background has a strong influence on metastasis susceptibility in breast cancer mouse models. Single nucleotide polymorphisms (SNP) in the Sipa1 gene are associated with metastasis in mice and human breast cancer patients. Consistent with this observation, we have shown that Sipa1 regulates metastasis in breast cancer cells; however, the molecular mechanisms remain largely unknown.
We identified several potential binding partners of SIPA1 in a yeast-two-hybrid screen, and confirmed interactions of SIPA1 with BRD4, RRP1B and SUN2 in subsequent experiments. Our analysis suggests that several complexes of SIPA1 exist in different compartments of the cell. A structure-function analysis that we have begun to carry out indicates that Sipa1 regulates metastasis in several ways, depending on its interaction partners and subcellular localization. Furthermore, the enzymatic GTPase-activating function of Sipa1 appears to play a critical role in regulating metastasis. These results could facilitate developing novel therapeutic approaches for the treatment of metastatic breast 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 5269. doi:10.1158/1538-7445.AM2011-5269
Abstract 5278: Intravital dual-colored visualization of colorectal liver metastasis formation in the living mice using two photon laser scanning microscopy
Authors: Tanaka Koji , Morimoto Yuhki , Matsushita Kohei , Kawamura Mikio , Toiyama Yuji , Saigusa Susumu , Okugawa Yoshinaga , Koike Yuhki , Inoue Yasuhiro , Miki Chikao , Mizoguchi Akira , Kusunoki Masato 
Published: June 2012

Abstract
Background and aim: Metastatic spread is the major cause of mortality in patients with colorectal cancer (CRC). Liver metastasis is the most frequent and thus the main therapeutic target in metastatic CRC patients. The mechanism of colorectal liver metastasis (CLM) is still poorly understood. In this study, we presented high-resolution images of dynamics of tumor-host interaction in liver metastasis model of the living mice using two photon laser scanning microscopy (TPLSM). We also visualized the formation of CLM from single cancer cells to micrometastatic colonies in the same mice by intravital TPLSM at several times.
Materials and methods: Red fluorescent protein (RFP) expressing SL4 murine colorectal cancer cell line (RFP-SL4) and green fluorescent protein (GFP)-transgenic mice (GFP mouse) were used as syngeneic tumor model. RFP expressing HT29 human colorectal cancer cell line (RFP-HT29) and GFP nude mice (C57BL/6-BALB/c-nu/nu-EGFP) were used as xenogeneic tumor model. 1×106 RFP expressing cancer cells were injected into the spleen of GFP (nude) mice for an experimental liver metastasis model. Intravital TPLSM was performed by exteriorizing the liver lobe of living mice and fixing it with a solder lug terminal and an adhesive agent (organ stabilizing system, patent number: 2007-129723). Interval TPLSM was also performed for intravital TPLSM at several times in the same mice.
Results: Viable cancer cells in the vital liver of living mice were successfully imaged at high-resolution in vivo real-time by TPLSM. Single cancer cells were arrested within hepatic sinusoids 2 hours after injection at a magnification of X600∼X1200. Platelet aggregation surrounding a single cancer cell was observed 2h after injection, indicating a phenomenon of tumor-cell induced platelet aggregation (TCIPA). Cancer cells were extravasated from hepatic sinusoid to Disse space 24h after injection. Protrusions of a Kupffer cell surrounding a cancer cell were observed, indicating that a Kupffer cell appears to be phagocytosing a cancer cell. RFP-SL4 were formed micrometastatic colonies with extensive stromal reaction. Liver metastasis of RFP-HT29 was observed as a clustering of micrometastatic nodules.
Conclusions: Our advanced technique using both intravital and interval TLPSM enables a dynamic high-resolution imaging of not only tumor-host interaction in cancer metastasis, but also metastatic process from a single cancer cell to micrometastasis formation in the living animals.
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 5278. doi:10.1158/1538-7445.AM2011-5278