bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5174: HYAL4: a new player in bladder cancer progression and diagnosis
Authors: Escudero Diogo O. , Knapp Judith , Lokeshwar Soum , Manoharan Murugesan , Soloway Mark , Lokeshwar Vinata B. 
Published: June 2012

Abstract
BACKGROUND: Hyaluronidase (HAase) family of enzymes degrades hyaluronic acid (HA). In the human genome there are 6 HAase genes clustered on chromosomes 3p21.3 (HYAL-1, -2, -3) and 7q31.3 (HYAL-4, PH20, HYALP1). While PH20 and HYAL-2 are testicular and lysosomal HAases, HYAL1 is a tumor-derived HAase. HYAL1 promotes tumor growth, invasion, and angiogenesis and is a diagnostic and prognostic marker for bladder cancer (BCa). The expression of other HAases has not been investigated in either normal cells or tumor cells and tissues. In this study we examined the expression of all 6 HAases in bladder tissues, cells and urine.
METHODS: Using time RT-PCR, we examined the mRNA levels of 6 HAase genes in BCa cell lines, 59 bladder tissues (normal (NBL) = 22; tumor (TBL) = 37) and 160 urine specimens (BCa = 52; normal = 18; history of BCa = 30; benign conditions = 59). The levels were normalized to β-actin. HYAL1 and HYAL4 were localized in bladder tissues by immunohistochemistry using anti-HYAL1 and anti-HYAL4 antibodies, respectively. The staining was graded for intensity (0 – 3) and area of staining. HYAL4 function was analyzed by siRNA transfection of HT1376 and HT5637 cell lines.
RESULTS: HYAL1, HYAL4 and HYALP1 mRNA levels were significantly (6-13-fold) elevated in TBL tissues (12.5 ± 2.7; 29.7 ± 21.9; 26.7 ± 21.9) when compared to NBL tissues (1.2 ± 0.6; 2.2 ± 2.4; 4.2 ± 6.6; P 0.05). cDNA cloning revealed that HYALP1 is a pseudo gene that encodes a non-functional truncated protein. HYAL1 and HYAL4 staining was significantly elevated in TBL tissues (188 ± 57; 232 ± 91) when compared to NBL tissues (68.5 ± 21.3; 93 ± 46; P &lt; 0.001). The staining for both HAases was exclusively localized in tumor cells. When compared to HYAL3, PH20, and HYAL2 mRNA levels, HYAL1, HYAL4 and HYALP1 mRNA levels were significantly elevated in BCa patients’ urine (P &lt; 001). Urinary HYAL4 mRNA levels had higher sensitivity (78.9%) and specificity (86.2%) than HYAL1 mRNA levels (72.3%; 76.2%) to detect BCa. Both HAases detected high-grade BCa with 83% – 86% sensitivity. Down regulation of HYAL4 expression by siRNA decreased proliferation of HT1376 and HT5637 cells (2.3-fold) and induced apoptosis (2.6-fold).
Conclusion: This is the first study showing that, like HYAL1, HYAL4 is a tumor derived HAase that is exclusively expressed in BCa cells. HYAL4 may be a potentially accurate marker for BCa diagnosis and may promote BCa growth and progression.
Support: Grant NCI/NIH R01 CA-72821-09; Bankhead Coley Cancer Research Program Sylvester Comprehensive Cancer Center and CURED
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 5174. doi:10.1158/1538-7445.AM2011-5174
Abstract 5175: Predictors of metastatic spread and progression free survival in uterine papillary serous carcinoma: A pilot study
Authors: Schuler Kevin M. , Banet Natalie , Bae-Jump Victoria , Lininger Ruth , Gehrig Paola A. 
Published: June 2012

Abstract
Background: Uterine Papillary Serous Carcinoma (UPSC) comprises 5-10% of all endometrial cancers but is responsible for nearly 40% of all endometrial cancer-related deaths. Progression-free survival (PFS) controlled for stage is also markedly shorter in UPSC compared to Type 1 endometrial cancers. Unlike endometrioid carcinoma, in which depth of myometrial invasion, grade, and lymphovascular space invasion (LVSI) are risk factors for extrauterine spread, UPSC often metastasizes in those with no myometrial invasion.
Objective: The objective of this study is to identify markers that may predict metastatic disease in women with non-invasive UPSC or portend a shorter progression free survival.
Materials: A retrospective chart review was performed on women diagnosed with Stage IA or Stage III/IV UPSC without myometrial invasion from 1995-2008. Examined factors include age, parity, race, weight, LVSI, CA125 levels, and tumor location within the endometrium. Tissue microarrays (TMAs) were constructed using paraffin blocked specimens and stained for ER, PR, p53, VEGF, Claudin 3, Claudin 4, Her-2/neu, Her-3, Synuclein gamma, and Maspin. Chi-square analysis, Student's t-test, and Fisher's Exact analysis were used where appropriate to detect statistically significant differences in these 2 groups with Kaplan-Meyer analysis used to determine PFS. Significance was represented at p&lt;0.05.
Results: Thirty-two patients were identified to have UPSC without myometrial invasion, 24 (75%) comprising Stage IA and 8 (25%) having Stage III/IV disease. Pathology blocks were available for 21 patients (14 Stage I and 7 Stage III/IV). CA125 was the only factor to achieve significance (p=0.04) in predicting metastatic spread; biomarkers, either alone or in combination, were not predictive of metastatic disease. In Stage I disease, positive ER status was associated with a significantly longer PFS (p&lt;0.001) while in Stage III/IV disease, positive Her-3 status was associated with a shorter PFS (p=0.014).
Conclusions: In addition to traditional risk factors not being predictive of metastatic disease, molecular markers that have been associated with metastatic disease and a worsening prognosis do not appear to be predictive in UPSC. However, the contribution of ER status and Her-3 needs to be further evaluated as this may offer new insight into therapeutic options for treatment.
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 5175. doi:10.1158/1538-7445.AM2011-5175
Abstract 5177: Primary tumor induces lymphangiogenesis and immune suppression in sentinel lymph nodes
Authors: Chikamatsu Kazuaki , Ishii Hiroki , Sakakura Koichi , Miyata Masanori , Masuyama Keisuke 
Published: June 2012

Abstract
The main factor that affects the prognosis of patients with squamous cell carcinoma of the head and neck (SCCHN) is regional lymph node metastases, which usually spreads first to the sentinel lymph nodes (SLNs). Recent studies using animal models have demonstrated that tumor cells can induce lymphangiogenesis in SLNs before metastasizing. In this study, we investigated the association of SLN lymphangiogenesis with the status of primary tumors. Moreover, the immunological status of SLNs was also examined. The expression of lymphatic-specific markers, including VEGFR-3, Prox-1, and LYVE-1 in 23 metastasis-negative SLNs obtained from 10 patients with SCCHN was investigated using quantitative real-time RT-PCR. Moreover, primary tumors obtained from patients were evaluated for the expression of VEGF-A, -C, and -D by immunohistochemistry. The level of LYVE-1 expression in SLNs was significantly higher than in control lymph nodes from patients with non-cancerous diseases. Moreover, SLNs from patients with VEGF-C-positive tumor showed a significantly higher expression of VEGFR-3 than those from patients with VEGF-C-negative tumor. VEGFR-3 is expressed mainly in lymphatic endothelium but also in a subset of antigen-presenting cells including immature dendritic cells (DCs), therefore; we furthermore examined the infiltration of DCs into SLN by immunohistochemistry. Interestingly, S-100+ and CD1a+ immature DCs infiltrated significantly into SLNs compared to non-SLNs in patients with SCCHN, suggesting that predominant migration of immature DCs, which suppress T-cell activation and support regulatory T cell development, would contribute to inhibit rather than develop anti-tumor immunity. Our findings suggest that primary tumor actively induces lymphangiogenesis in SLNs prior to the onset of metastases, and where tumor-derived VEGF-C plays an important role. Moreover, active lymphangiogenesis may concomitantly lead to down-regulation of SLN immunity. Thus, both lymphangiogenesis and immune suppression in SLNs are likely the basis of its susceptibility to tumor metastases.
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 5177. doi:10.1158/1538-7445.AM2011-5177
Abstract 5178: Expression of CD44/CD24 and aldehyde dehydrogenase 1 in resected breast cancer: CD24-positivity predicts early relapse
Authors: Moon Yongwha , Koo Ja Seung , Han Hyunju , Park Byeong-Woo , Kim Seung Il , Park Seho , Kim Joo-Hang , Sohn Joo Hyuk 
Published: June 2012

Abstract
Background: CD44+/CD24- or aldehyde dehydrogenase 1 (ALDH1) has been suggested as potential markers for breast cancer stem cells, although little is known about its clinical implications. We evaluated the expression of CD44/CD24 and ALDH1 in breast cancer patients in both ends of the prognostic spectrum.
Methods: Of 819 resected breast cancer cohort with positive estrogen receptor, ‘early relapse group’ within 5 years postsurgery and ‘no relapse group’ longer than 10 years postsurgery were defined. Paraffin-embedded tumor tissues were available in 31 early relapsed patients and 68 patients from no relapse group. CD44/CD24 and ALDH1 expression were evaluated with immunohistochemical staining. Positive criteria were designated as more than 15% tumor cell membranous staining for CD44/CD24 and more than 5% tumor cell cytosolic staining for ALDH1.
Results: Early relapse group contained higher N stage and higher histologic grade than no relapse group but there were no differences in age, menopauseal status, progesterone receptor status, HER2 status, and T stage between both groups. Phenotypes of CD44/CD24 were CD44+/CD24- in one patient (1%), CD44+/CD24+ in one (1%), CD44-/CD24+ in 12 (12%), and CD44-/CD24- in 67 (68%). Four patients (4%) showed ALDH1-positivity. Due to rarity of CD44-positivity or ALDH1-positivity, staining results were simply dichotomized into CD24-positive (13%, 13/99 patients) and CD24-negative status (87%, 86/99 patients) and only the status of CD24 was further analyzed. CD24-positivity was higher in early relapse group (32%) than in no relapse group (4%). CD24-positivity was associated with negative progesterone receptor (P=0.026), higher N stage (P=0.029), and higher histologic grade (P=0.034). However, in the multivariate logistic regression adjusted by known prognostic factors, CD24-positivity was a still significant predictive factor for early relapse (hazard ratio=8.51; P=0.006).
Conclusions: The incidence of CD44+/CD24- and ALDH1-positivity which are potential breast cancer stem cell markers, were low. However, in resected breast cancer, expression of CD24 was a significant predictive factor for early relapse. CD24 is worth further investigation as a novel biomarker.
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 5178. doi:10.1158/1538-7445.AM2011-5178
Abstract 5192: The mobilization and recruitment of bone marrow-derived stem cells contributes to the acceleration of tumor growth after surgery
Authors: Takemoto Yoshihiro , Li Tao-Sheng , Kubo Masayuki , Ohshima Mako , Ueda Kazuhiro , Harada Eijirou , Uesugi Naomasa , Enoki Tadahiko , Hamano Kimikazu 
Published: June 2012

Abstract
Background. Although surgical resection of the primary tumor lesion is still the most promising strategy for cancer therapy, surgical injury may accelerate tumor growth and metastasis, negatively affecting patients’ prognosis. Previous studies have demonstrated that many factors, including the robust release of cytokines and temporal changes of immunological and inflammatory mediators may contribute to the acceleration of tumor growth and metastasis after surgery. However, the precise mechanisms are not yet fully understood. We tested the hypothesis that surgical injury induces mobilization and recruitment of bone marrow-derived stem cells, thereby enhancing angiogenesis and accelerating tumor growth.
Methods. Mice were subjected to partial gastrectomy, and non-gastrectomized mice were used as controls. Mobilization of bone marrow stem cells was monitored after surgery. Using an established tumor model in GFP+ bone marrow-transplanted chimera mice, we further investigated whether the mobilized stem cells affected tumor growth. To evaluate the influence on tumor growth of surgical injury and the inhibition of SDF-1/CXCR4 signals, we used AMD3100, a CXCR4 antagonist.
Results. Compared to control, gastrectomy significantly increased the populations of CD34+ cells (6.9±4.5% vs 3.3±0.4%, p&lt;0.05) and CD34+/Flk-1+ cells (0.08±0.02% vs 0.05±0.01%, p&lt;0.05) in peripheral blood 12 hours after surgery. Twelve days after surgery, the tumor volume was almost double in gastrectomized mice compared with control (580±106 mm3 vs 299±162 mm3, p&lt;0.05). Histological analysis of tumor tissue revealed that the microvessel density and number of proliferating cells were significantly higher, but those of apoptotic cells were significantly lower, in gastrectomized mice as compared with control. Furthermore, the number of GFP+ cells found in tumor tissue was significantly larger in mice that underwent gastrectomy than in control. Some of the stained GFP+ cells were positive for CD34 and had been incorporated into microvessels. However, administration of AMD3100 significantly inhibited the recruitment of GFP+ cells and completely negated the acceleration in tumor growth after surgery (345±172 mm3, p&lt;0.05).
Conclusion. Surgical injury induces mobilization and recruitment of bone marrow stem cells, thereby enhancing angiogenesis and accelerating tumor growth. Temporary inhibition of the SDF-1/CXCR4 signals may represent new therapeutic strategies for preventing acceleration of tumor growth after surgery.
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 5192. doi:10.1158/1538-7445.AM2011-5192
Abstract 5205: Selectively high Wnt pathway activity in subpopulations of colon cancer cells and its significance for tumor initiation
Authors: Horst David , Shivdasani Ramesh A. 
Published: June 2012

Abstract
Several cell surface markers that are reported to enrich for tumor-initiating colon cancer cells are presumed targets of the canonical Wnt/beta-catenin pathway. Furthermore, colon cancers typically express the Wnt-effector beta-catenin in a heterogeneous pattern, with strong nuclear expression detected only in a small fraction of tumor cells. We therefore hypothesized that high beta-catenin expression and Wnt pathway activity mark a tumorigenic subpopulation. To label viable tumor cells according to the level of Wnt pathway activity, we constructed lentiviral vectors that express GFP under control of an optimal, beta-catenin-responsive TCF/LEF1 promoter (TOP-GFP). We transduced primary colon cancer xenografts and two well characterized colon cancer cell lines with these vectors, used flow cytometry to isolate cell subpopulations with differential GFP expression, and examined these subpopulations for tumorigenicity and gene expression. High GFP expression accurately marked tumor cells with nuclear beta-catenin immunostaining in Caco2 but not SW1222 cells and in a fraction of primary colon cancer xenografts. Gene expression analysis in the concordant cases was consistent with increased Wnt-pathway activity within the GFP-high cell population, including high expression of the putative stem cell markers CD133, CD44 and LGR5. In SW1222 cells and some primary tumor xenografts, the GFP-high fraction correlated poorly with nuclear beta-catenin localization and GFP flow cytometry did not separate cells with a gene expression profile suggesting Wnt pathway activity. Among these various sources, only Caco2 cells showed increased tumorigenicity of GFP-high cells in immunodeficient mouse xenografts. The utility of TOP-GFP and related reporters to identify tumor-initiating colon cancer cells with high Wnt activity thus varies among primary human colorectal tumors and established cell lines. Furthermore, Wnt pathway activity might fluctuate substantially within individual tumor cells. We conclude that high Wnt activity among tumor cell subpopulations does not necessarily signify tumor-initiating potential.
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 5205. doi:10.1158/1538-7445.AM2011-5205
Abstract 5208: Simultaneous color-coded imaging to distinguish colon cancer stem-like and non-stem cells in the same tumor
Authors: Suetsugu Atsushi , Hassanein Mohamed K. , Nagaki Mashito , Moriwaki Hisataka , Bouvet Michael , Moossa Abdool R. , Hoffman Robert M. 
Published: June 2012

Abstract
In this study, CD44+ HCT-116 cells were considered as colon cancer stem-like cells (CSCs) and CD44− HCT-116 cells were considered colon non-cancer stem cells (NCSCs). CD44+ cells were isolated by magnetic bead sorting. CD44+ cells outgrew CD44− cells in vitro. GFP-CD44+ cells preferentially migrated from the center of the spheroids after co-culture with RFP-CD44− cells. GFP-CD44+ cells grew to a greater extent subcutaneously in nude mice, when compared to the CD44− cells. Equal numbers of GFP CSCs and the RFP NCSCs were mixed and co-injected in the spleen of nude mice where the cells metastasized to the liver. GFP CSCs were found in greater numbers compared to RFP NCSCs in the liver of nude mouse. GFP CSCs and RFP NCSCs were co-injected in the wall of the cecum. GFP CSCs were observed in metastases formed in the small intestine and colon wall, to a much greater extent than RFP-NCSC. Simultaneous color-coded imaging of CSCs and NCSCs in the present study has demonstrated two very different subsets of cells within the HCT-116 cell line with respect to tumor growth and 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 5208. doi:10.1158/1538-7445.AM2011-5208
Abstract 5219: The LIM protein LIMD2 functions as an effector and biomarker for metastasis in multiple tumor types
Authors: Peng Hongzhuang , Hou Zhaoyuan , He Mei , Kebebew Electron , Orntoft Torben F. , Herlyn Meenhard , Caton Andrew J. , Fredericks William J. , Malkowicz Bruce , Rauscher Frank J. 
Published: June 2012

Abstract
The LIM domain is found in proteins from a wide variety of eukaryotic organisms. The LIM domain is organized as a tandem zinc-finger structure that functions as a modular protein-binding interface. LIM domain containing proteins have diverse cellular roles such as regulators of gene expression, cytoarchitecture, cell adhesion, cell motility, signal transduction, and biosensors. LIMD2 belongs to the LIM only family of LIM proteins and was identified as a biomarker for papillary thyroid carcinoma lymph node metastasis from molecular profiling of matched samples. However, the biological function of LIMD2 remains unknown. To identify whether LIMD2 is a biomarker for other cancers, highly specific LIMD2 polyclonal and monoclonal antibodies were developed and several cancer cell lines were tested for LIMD2 expression. These cancer cell lines were derived from breast cancer, melanoma, bladder cancer, and thyroid cancer. We found that the cancer cell lines derived from more aggressive tumors exhibited higher levels of LIMD2 protein expression. Furthermore, cells expressing higher levels of LIMD2 had increased migratory capabilities. Over-expression of LIMD2 protein in the less aggressive bladder cancer cell line (RT4) showed an increase in migration and colony formation ability. Conversely, knockdown of LIMD2 using siRNA decreased the migratory ability of the malignant melanoma cancer cell line and caused morphological changes in these cells. These data not only underscore the importance of LIMD2 as a key metastatic biomarker, but also suggest that LIMD2 may play a functional role in tumorgenicity. LIMD2 may also serve as a novel anti-metastatic target to improve the efficacy of conventional cancer therapeutics.
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 5219. doi:10.1158/1538-7445.AM2011-5219
Abstract 522: CXCR4 inhibition sensitizes prostate cancer cells to conventional chemotherapy in an in vitro co-culture model
Authors: Domanska Urszula M. , Kruizinga Roeliene C. , Nagengast Wouter B. , Bosscha Hetty Timmer – , de Vries Elisabeth G.E. , Huls Gerwin A. , Walenkamp Annemiek M.E. 
Published: June 2012

Abstract
Background: Chemokine receptor 4 (CXCR4) mediates homing of hematopoietic stem cells to niches, where stromal cells express CXCL12, the CXCR4 ligand. Indeed, in clinical practice the CXCR4 inhibitor AMD3100 is used to mobilize hematopoietic stem cells. Also in several solid cancer types, including prostate cancer, tumor cells show CXCR4 overexpression. In solid cancers this receptor is involved in tumor metastasis, invasiveness and primary tumor growth. It is postulated that in these tumors, the stromal microenvironment expressing CXCL12, protects tumor cells from chemotherapy. We therefore aimed to study whether inhibition of the CXCR4/CXCL12 axis, with the specific CXCR4 inhibitor AMD3100, sensitizes prostate cancer cells for conventional chemotherapy and improves treatment outcome.
Methods: A co – culture model of murine stroma (MS5) and human prostate cancer cells (PC3-luc) has been developed. To assess the effect of stromal cells on sensitivity to chemotherapy, PC3-luc cells labeled with fluorescent DiI dye were cultured with or without MS5 cells and treated with 1 μM docetaxel for 40 hours. To determine whether observed effect can be reversed by CXCR4 inhibition, experiments were repeated with addition of 25μg/ml AMD3100. After 40 hours treatment, the percentage of viable PC3-luc cells in the field of view was assessed by fluorescent microscopy with DAPI nuclear staining. For each condition, six fields of view were counted and the average percentage was calculated. Experiments were performed in three repetitions.
Results: In the absence of MS5 stromal cells, docetaxel treatment of PC3-luc cells resulted in only 14.1 % survival. Co-culturing with stromal cells demonstrated a protective effect on chemotherapy induced cell death, with up to 61,8 % survival of PC3-luc cells after docetaxel treatment. AMD3100 eversed this protective effect completely, as combined treatment with AMD3100 and docetaxel in the co-culture setting resulted in a drop in the percentage of viable cells from 61.8 % to 19.9 % (P&lt;0.0042).
Conclusion: Murine stromal MS5 cells protect PC3-luc tumor cells against docetaxel – induced cell death in an in vitro co-culture system. Treatment with AMD3100 almost completely abolished the effect of the presence of stromal cells when the prostate cancer cells were treated with docetaxel. These data underscore the relevance to focus for further research on the role of CXCR4 inhibitors as a potentiating adjunct to conventional chemotherapy.
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 522. doi:10.1158/1538-7445.AM2011-522