bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P1-01-32: Usefulness of Clinical Exploration, Ultrasound and MRI for the Assessment of Axillary Lymph Nodes Status Previous to the Performance of Sentinel Node Depends on Tumor Molecular Subtype
Authors: Sabadell D , Vernet-Tomas MDM , Colome C , Rodriguez-Arana A , Plancarte F , Carreras R. 
Published: April 2011

Abstract
Introduction: A high detection of positive lymph nodes previous to the surgical procedure lowers the probability of a false negative sentinel node. The sensibility and specificity of different imaging methods could depend on the molecular features of each tumor
Objective: The aim of this study was to study sensibility and specificity of clinical exploration, ultrasound and MRI to assess the status of axilar lymph nodes in different molecular subtypes.
Material and Methods: we retrospectively reviewed T1 and T2 breast cancers not candidate for neoadjuvant chemotherapy, treated in our breast cancer unit from September 2008 to May 2010. Data on clinical exploration (CE), axillary ultrasound (AU) and MRI were reviewed for each patient. The pathology exam of the surgical specimen (sentinel node or lymph node dissection) was reviewed for each patient and sensibility and specificity were calculated for each exploration method. Sensibility and specificity were also calculated separately considering five different molecular subtypes: Tubular A, Tubular B, Triple negative tumors, cerbB2 positive tumors and lobular tumors.
Results: 290 patients with T1 and T2 breast cancer were included in the study. Sensibility for CE was 26.76% and specificity 91%. Sensibility for AU was 38.46% and specificity 86.81%. Sensibility for MRI was 44.06% and specificity 86.02%. For Tubular A tumors, the highest sensibility was for MRI (40%) and the best specificity for CE (91.35%). For Tubular B tumors, the highest sensibility was for CE (33.33%) and the highest specificity for AU (100%). For Triple negative tumors, the highest sensibility was for MRI (100%) and the highest specificity for CE (89.47%). For cerbB2 tumors, the highest sensibility was for MRI (75%) and the highest specificity was for CE (100%). For Lobular tumors, the highest sensibility and specificity were for AU (50% and 93.33%, respectively).
Conclusion: MRI is the exploration with a higher sensibility to assess the preoperative status of axillary lymph nodes considering all the tumors together and in Tubular A, Triple negative and cerbB2 positive tumors. MRI sensibility is specially high in Triple negative and cerbB2 positive tumors. When choosing different imaging methods to assess axilar status, molecular subtype should be considered.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-01-32.
Abstract P1-02-01: Vasohibin-1 in Human Breast Carcinoma: A Potential Negative Feedback Regulator of Angiogenesis
Authors: Tamaki K , Ishida T , Miyashita M , Sato Y , Tamaki N , Ohuchi N , Sasano H. 
Published: April 2011

Abstract
Background: Vasohibin-1 is a recently identified negative feedback regulator of angiogenesis induced by vascular endothelial growth factor (VEGF)-A. This is the first study to evaluate immunoreactivity and mRNA expression of Vasohibin-1 in human breast disorders. Material and Methods: We examined 251 breast specimens including invasive ductal carcinoma (IDC: 148), ductal carcinoma in situ (DCIS:62), fibroadenoma (FA:16), inflammatory lesion (6), fibrocystic change(9) and non-pathological breast tissue(7). We immunolocalized vasohibin-1 and compared its immunoreactivity to that of VEGF-A, VEGF receptor 2 (Flk-1), CD31 and Ki-67. The correlation of vasohibin-1 immunoreactibity with overall survival (OS), and disease free survival (DFS) of the breast carcinoma patients was also evaluated. In addition, we evaluated Ki-67 and CD31, and Ki-67 and vasohibin-1 double-immunostaining for further characterization of neovascularization. We also evaluated mRNA expression of Vasohibin-1 using a real-time quantitative RT-PCR with LightCycler system.
Results: Vasohibin-1 was detected in endothelial cells of human breast and its immunodensity was significantly higher in IDC and inflammatory lesion than the other types (P&lt;0.001). As for DCIS, there was a significant positive correlation between vasohibin-1 expression level and nuclear grade or Van Nuys classification of carcinoma cells (P&lt;0.001). In addition, a significant positive correlation was detected between vasohibin-1 and VEGF-A, Flk-1 or Ki-67 (P&lt;0.001). There was also positive associations between vasohibin-1 and OS (P=0.004) and DFS (P&lt;0.001). Results of double-immunostaining demonstrated the ratio of Ki-67-positive cells among vasohibin-1-positive endothelial cells (46.5%) was significantly higher than those among CD31-positive cells (23.5%). In addition, there was a significant positive correlation between Vasohibin-1 mRNA level and Ki-67 or high nuclear grade(P&lt;0.001).
Discussion: This is the first study demonstrating the status of vasohibin-1 in human breast lesions, which indicates that vasohibin-1 is associated with neovascularization and may especially play important roles in the regulation of intratumoral angiogenesis in human breast cancer. Vasohibin-1 is supposed to be induced in the downstream of VEGF-A/Flk-1 signaling pathway and considered an appropriate biomarker for intratumoral neovascularization. In addition, these results clearly indicated that vasohibin-1 expression may become one of the prognostic markers for metastasis and prognosis, and also become one of the appropriate biomarker of the potential of subsequent stromal invasion of carcinoma cells.
Figures available in online version.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-02-01.
Abstract P1-02-04: The Influence of Matriptase-2 on Angiogenesis and Tumour Growth In Vivo.
Authors: Webb SL , Sanders AJ , Mason MD , Jiang WG. 
Published: April 2011

Abstract
Background: Metastasis is a key part of cancer progression and angiogenesis plays a large role in the ability of cancer cells to spread around the body and in the progressive growth of the primary tumour. Matriptase-2 is a cell surface serine protease believed to have implications in cancer metastasis. The current study aims to assess the importance of matriptase-2 in angiogenesis and tumour growth, using in vitro and in vivo models. Methods: Matriptase-2 was over-expressed in the HECV endothelial cell line, previously displaying minimal matriptase-2 expression, through the transfection of a mammalian expression construct containing the full coding sequence for matriptase-2. Following verification of forced expression, the cellular effects of matriptase-2 were examined using a number of in vitro cell models. The effect of matriptase-2 over-expression was also examined in in vivo mouse models by co-delivery of endothelial cells and tumour cells.
Results: Matriptase-2 significantly reduced the motility (46.47±16.18 vs 10.93±2.80 p=&lt;0.01) of the HECV cells and their ability to form tubule structures (23841.60±744.75 vs 9817.80±933.85 p=0.01) in an in vitro angiogenesis Matrigel tubule formation model. Matriptase-2 was found to have no significant effect on the growth (691.52±100.17 vs 763.50±91.43 p=0.110) and cell-matrix adhesion of the HECV cells (64.20±8.70 vs 57.42±4.50 p=0.530). However, the in vivo studies showed a reduction in tumour growth and development following co-injection of cancer cells with endothelial cells over-expressing matriptase-2 compared to co-injection with control endothelial cells. The sizes of tumours in two tumour models were: 70.99±19.52mm3 for tumour cells with control endothelial cells vs 0.17±0.10 mm3 for tumours with Matriptase-2 over-expression endothelial cells, p=&lt;0.01; and 80.41±18.31 mm3 vs 43.12±20.33 mm3 p=0.08, in the other tumour model.
Conclusion: Matriptase-2 appears to negatively influence angiogenesis through its inhibitory effect on endothelial cell motility and tubule formation. This is corroborated by the reduction of tumour growth, in vivo. Together this data suggests that matriptase-2 has an important role in the control of angiogenesis and tumour development.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-02-04.
Abstract P1-02-05: EPLIN? Can Negatively Impact on Angiogenesis and Is Associated with ERK Signalling
Authors: Sanders AJ , Ye L , Jiang WG , Mason MD. 
Published: April 2011

Abstract
Background: EPLIN (epithelial protein lost in neoplasm) is a cytoskeletal associated protein involved in regulating actin dynamics and cell motility. EPLIN expression is frequently lost in cells as they progress to a cancer state and this loss may account for enhanced cancer cell motility. EPLIN has also been shown to be lost in clinical breast cancer, which is associated with patients clinical outcome. Recently, EPLIN has been linked to ERK signalling. This study examined the potential of EPLIN to influence the angiogenesis process and its links to ERK in endothelial cells Methods: Over-expression of EPLIN α was achieved through transfection of the vascular endothelial cell, HECV, with a mammalian expression construct containing the full coding sequence of EPLINα. Enhanced levels of EPLINα were verified through RT-PCR, Q-PCR and Western blot analysis before assessing the angiogenic potential of control and transfected cells using angiogenesis and cell migration models. Treatment of transfected and control cells with ERK inhibitor was used to assess the potential interaction between EPLINα and ERK in endothelial cells. Results: Substantial enhancement in EPLINα expression was seen in transfected cells compared to control cells at both transcript and protein level. Over-expression of EPLINα in HECV endothelial cells resulted in a reduced capacity, compared to control, of these cells to form tubule like structures in an in vitro angiogenesis tubule formation assay (6566 +/− 856µm tubule perimeter of control cells vs 2881 +/− 546µm EPLINα overexpressing HECV cells, p = 0.007). This was seen together with a reduced cell migration following overexpression of EPLINα in the cells. Treatment of control cells with ERK inhibitor significantly reduced tubule formation (3537 +/− 277µm tubule perimeter of ERK inhibitor treated control cells vs 6566 +/− 856µm total perimeter of untreated control cells, p = 0.01), however treatment of HECV cells transfected with EPLINα expression construct caused tubule formation levels to return to control levels (6566 +/− 856µm tubule perimeter of untreated control cells vs 5326 +/− 784µm tubule perimeter of ERK inhibitor treated EPLINα overexpressing HECV cells, p = 0.317).
Discussion: EPLINα can negatively influence tubule formation in vitro and thus may impact on the angiogenesis process. Furthermore, its impact on tubule formation appears to be linked to ERK signalling. Together, this study suggests a role for EPLINα in angiogenesis, which may be linked with ERK signalling.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-02-05.
Abstract P1-03-09: Combination of nab-Paclitaxel and Bevacizumab Inhibited Tumor Growth and Metastasis of New Inflammatory Breast Cancer Models
Authors: Volk LD , Wilber A , Trieu V , Desai N , Ran S. 
Published: April 2011

Abstract
Background: Inflammatory breast cancer (IBC) is a highly lethal form of breast cancer which is characterized by skin redness, irritation, swelling, pain, as well as extensive lymph nodes (LN) and hematogenous metastasis. Animal models of IBC are highly desirable for studying its pathology and for designing effective therapies. In this study, we established two new luciferase-and fluorescently-labeled IBC models and tested the efficacy of the novel drug combination nab-paclitaxel and bevacizumab. Methods: Inflammatory SUM149 breast cancer cells were stably transfected with Red Fluorescent Protein (RFP) and Renilla luciferase to establish SUM149-RR, or infected with lentivirus encoding Green Fluorescent Protein (GFP) and Firefly luciferase to establish SUM149- GL. The new cell lines were characterized both in vitro and in vivo. Immunodeficient mice bearing SUM149-RR tumors of 150mm3 in size were treated with saline (control), bevacizumab (4 mg/kg, i.p., twice a week, for 10 weeks), nab-paclitaxel (10 mg/kg, i.v., qdx5), or the combination. Metastasis was analyzed by measuring luciferase activity in the lymph nodes (LN) and lungs.
Results: Luciferase measurements and in vivo imaging showed that both SUM149-RR and-GL clones were highly metastatic to LN, lungs, liver, brain, and spleen. SUM149-RR tumors in control mice displayed ulcerations, edema and redness similar to the clinical disease, while tumors in mice treated with bevacizumab or combination therapy showed no signs of inflammation. Bevacizumab alone decreased tumor growth at later but not early stages of tumor growth, whereas nab-paclitaxel alone inhibited tumor growth by 73%. Combination therapy increased inhibition to 96%, and resulted in 22% (2/9) complete responses. Histologically, tumors from bevacizumab treated groups were more morphologically intact with reduced vascular abnormalities than tumors from control or nab-paclitaxel treated mice. LN and lung metastasis was significantly reduced in all treated groups as compared with control.
Conclusions: The SUM149-RR and SUM149-GL lines are new double-tagged models of human IBC that allow organ visualization and accurate quantification of metastasis. These models can be used to study the biology and treatment of IBC. Combination of nab-paclitaxel with bevacizumab was highly effective against SUM149-RR, suggesting the potential usefulness of this regimen for treatment of IBC patients.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-03-09.
Abstract P1-03-10: A Model To Prevent Pregnancy Associated Breast Cancer: The Effect of HCG on Tumorigenesis in MMTVneu Mice
Authors: Rouzier R , Vercambre-Donck M , Wafo E , Uzan S , Aractingi S. 
Published: April 2011

Abstract
Background: HER2 expression is associated with increased parity-induced risk of breast cancer in women, and women that have been pregnant and have breastfed acquire a 4.2-fold increased risk of developing HER2- positive breast cancers than their counterparts that never breastfed. The mechanisms responsible for the increased risk of developing HER2- positive breast cancer following pregnancy and lactation remain to be elucidated. Animal and ‘in vitro’ experiences show that human chorionic gonadotropin (hCG) is capable to protect from breast cancer. The aim of this study was to assess the effect of HCG and pregnancy on tumorigenesis in MMTVneu mice and to study the mechanisms in terms of differentiation and stem cells depletion.
Methods: Mice were intraperitoneally injected BrdU then intraperitoneally injected HCG. Mice were sacrificed for the detection of label retaining cells. The two inguinal groups of mammary gland were dissected. For each gland, ducts and lobules were identified and drawn manually. We used Mercatorâ software for morphometry: ductal and lobular surface were measured and reported to the surface of the selected region. Cells retaining the label after 8-10 weeks (adulthood) were identified as LRCs. A mammary gland tumor free survival was conducted. Results: We observed that the differentiation and maturation of the mammary gland caused by the HCG was different in MMTVneu mice and controls: whereas WT littermates presented with sleek ductal appearance before parity, increased lateral side branching and budding was observed in mammary gland ducts of the MMTV-neu females and WT receiving HCG. The effect of HCG was mediated by the ovary. The effect of HCG on the stem cell pool was limited. Early HCG exposition did not modify ErbB2/Neu-induced mammary tumorigenesis but had an independent tumorigenic effect.
Conclusion: Early stimulation with HCG does not mimic early parity. The tumor development was not different between MMTV-neu mice that received or not HCG. We observed an independent ovary mediated tumorigenic effect of early administration of HCG.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-03-10.
Abstract P1-03-12: The First Reproducible Model of Primary Human Ductal Carcinoma In Situ (DCIS) Using the Mouse Intraductal (MIND) Method
Authors: Valdez K , Smith W , Fan F , Medina D , Behbod F. 
Published: April 2011

Abstract
Past studies of the molecular mechanisms regulating human DCIS progression to invasion have been limited by a lack of suitable human models. The current models have not utilized primary human DCIS placed in their natural microenvironment, i.e., inside the mammary ducts, and do not mimic the heterogeneity of human DCIS. Previously, we reported the development of a mouse xenograft model using established breast DCIS cell lines, SUM-225 and DCIS.COM by the mouse intraductal (MIND) method. MIND involves injection of human DCIS cells into the primary ducts of immunodeficient mouse mammary glands via the nipple. In this study we demonstrate the reproducible growth of human primary DCIS cells derived from patient biopsy samples using the MIND model. Core biopsies from consenting patients are processed to isolate the epithelial cell component and injected. To date, 69 patients have consented to provide core biopsy tissue and we have received tissue from 38. Of these, 14 samples have been confirmed as positive for DCIS, and 2 as atypical hyperplasia, based on the pathology report of adjacent biopsies. The biopsy samples were heterogeneous with respect to ER, PR, Ki67, Her-2 and histology. A total of 24 mammary glands from immunodeficient mice have been injected with these cells and analyzed for growth by immunofluorescent (IF) with antibodies directed at human-specific cytokeratin-5 and/or 19 and smooth muscle actin.
Table 1. Summary of grewlh of human primary biopsies in (tie MIND xenograft
The average number of cells recovered per mg of tissue are shown in Table 1. Biopsies diagnosed as normal yielded only 91±34 cells/mg compared with most DCIS cases that showed an average cell number of 971 per mg tissue. Our results indicate that human DCIS and hyperplasia cells from biopsy samples are capable of growing within the NOD-SCID IL2Rgammanull (NSG) mouse mammary ducts. NSG mice mammary ducts are more suitable hosts for the growth of human primary DCIS cells, compared to SCID-Beige. Furthermore, the higher number of cells recovered following digestion predicted the positive DCIS growth rate. DCIS cells formed single and multi-layered epithelium inside the ducts and were heterogeneous with respect to the expression of human specific cytokeratins. The MIND xenografts recapitulated the patient's original DCIS as evidenced by IF staining for the biomarkers ER and Her-2 in the primary human biopsies and MIND xenografts. These results provide the first reproducible model of primary human DCIS for studying the temporal processes of early breast cancer progression. Future experiments will characterize the cellular basis for the subtypes of DCIS and delineate the distinct molecular and cellular mechanisms of early breast cancer invasion, and cancer stem cell growth and self-renewal.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-03-12.
Abstract P1-08-02: Short-Term Pregnancy Levels of Estradiol Delays Mammary Tumor Development by Altering PI3K/AKT Pathway in Her2/neu Mice
Authors: Parada JA , Arumugam A , Agullo P , Myers S , Delgado A , Boopalan T , Lakshmanaswamy R. , Paul L. 
Published: April 2011

Abstract
Approximately 20-30% of all breast cancers overexpress the human epithelial growth factor receptor 2 (Her2). Breast cancers that overexpress Her2 have been associated with a more aggressive phenotype and decreased survival. Currently, the FDA has only approved trastuzumab, a recombinant monoclonal antibody against the Her2 receptor, for treatment of Her2- overexpressing breast cancer. Even though trastuzumab has been effective, many breast cancers do not respond to treatment or they eventually progress to a resistant state. Hence, several research investigations are underway to identify therapies besides trastuzumab that could be used for the treatment of Her2-positive breast cancer. It has been earlier demonstrated that uniparous Her2/neu transgenic mice developed smaller mammary tumors and these tumors had significantly decreased metastatic potential. Also, we had earlier demonstrated that short-term treatment with pregnancy levels of estradiol was very effective in delaying tumor progression and decreasing tumor burden. In this present investigation, we have attempted to understand the molecular mechanisms underlying this anti-tumor effect of short-term pregnancy levels of estradiol treatment against Her2/neu driven mammary carcinogenesis. Seven week old activated Her2/neu (murine-mammary-tumor virus (MMTV)-c-neu) FVB transgenic mice were treated for 3 weeks with 100mg of estradiol in silastic capsules. We have shown that this dose of estradiol treatment mimics pregnancy levels of the hormone in circulation. Control animals received empty silastic capsules for the same duration. Mice were palpated once every week for nine months to monitor the development of mammary cancer. Histopathological examination was performed to confirm the carcinomatous nature of the palpable tumors. A group (n=3) of mice were terminated from control and estradiol treated groups immediately after three weeks of treatment, and also, at 6 and 12 weeks post withdrawal of the treatment. Mammary tumor and normal mammary tissue were excised, snap-frozen in liquid nitrogen and stored at −80°C. Protein and total RNA were extracted from these tissues. Pathway focused microarray analysis was done on the PI3K/AKT pathway. Results demonstrate that, in parous and estrogen treated mice, proteins and genes involved in tumor-suppression (Mtcp1,Rbl2,Srf and Ywhah) and immune response (Cd14,Tlr4) were upregulated; which have been shown to play a role in reducing tumors by induction of apoptosis. This trend in gene expression alteration is present in both normal and mammary tumor tissue in the estradiol treated and parous groups and demonstrates that short-term pregnancy levels estrogen is altering the PI3K/AKT pathway; which correlates with our previous findings that short-term estradiol treatment is effective in tumor delay.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-08-02.