bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P1-01-16: Evaluation of Sentinel Node Biopsy Using a Combined Dye and Fluorescence Method for Breast Cancer
Authors: Yamada A , Chishima T , Kimura M , Shimizu D , Hasegawa S , Ishikawa T , Endo I. 
Published: April 2011

Abstract
Background: Sentinel lymph node (SLN) dissection is now widely accepted for staging the axilla in patients with breast cancer. At present, several methods are used to detect SLN. A combination of blue dye and radioactive colloid has been described previously as a superior method for detecting SLN in breast cancer patients. However, use of radioactive colloids is not generally available for various reasons in Japan. SLN detection guided by indocyanine green (ICG) fluorescence could emerge as a new method for SLN biopsy. The aim of this study was to evaluate sentinel node biopsy using a combined dye and fluorescence method for breast cancer.
Methods: Fifty-eight patients with clinically node-negative breast cancer were examined between April 2008 and March 2009 at Yokohama City University Hospital. Intradermal injections of 20 mg/5 ml of indigo carmine and 0.5 mg/0.1 ml of ICG were made into the upper-lateral region of the periareolar area. Subcutaneus lymphatic channels draining from the areola to the axilla were visible under fluorescence within a few minutes. SLNs were then dissected under direct vision supported by fluorescence navigation. Palpable lymph nodes were also dissected. All SLNs were histologically evaluated by 2-mm serial section and staining with hematoxylin and eosin. Patients with positive SLNs underwent axillary lymph node dissection (ALND), while patients with negative SLN did not.
Results: SLNs were identified in 58 patients (100%). ICG fluorescence imaging was compared with indigo carmine dye, and SLNs were identified in 57 and 52 patients, respectively (detection rate: ICG, 98.3%; dye, 89.7%). The mean number of excised SLNs was 2.72. Mean numbers of lymph nodes showing fluorescence and blue stain from injected dye were 2.31 and 1.41, respectively. Eight of 58 patients (13.8%) had metastases detected in the SLN, so ALND were subsequently performed. Five of these cases were without metastases at non-SLN that were dissected. One patient showed metastasis in a SLN that was positive for fluorescence, but negative for blue dye. Among all cases, 1 patient (1.7%) showed an SLN without fluorescence or blue staining, and this case was detected by palpation only.
Conclusion: Combined use of dye and fluorescence method identified SLNs effectively.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-01-16.
Abstract P1-01-17: Comparative Analysis of Metastatic Tumor Cells within the Sentinel Lymph Nodes of Breast Cancer Patients Utilizing a Novel Approach
Authors: Zhang J , Liu Y , Ju J , Xu L. 
Published: April 2011

Abstract
Background and Objective: The intrinsic high false negative rate associated with intraoperative analysis of SLN may result in a second surgical procedure for the patient. We attempt to improve the intraoperative and the pathologic and molecular evaluation of SLN by utilizing novel immunobead methods for detection and assessment of tumor cell expression of Her2, CD44 and Muc1.
Methods: During the operation of breast cancer patients, gived sentinel lymph node biopsy firstly, and the SLN will each be divided in four quadrants, and two quadrants (B,C) will be brought to the pathologist for routine intraoperative analysis and further immunhistochemical (H&E and CK) examination often 2 mm thick sections of each quadrant.
The other (A,D) quadrants will be immediately mechanically disaggregated and filtered in order to remove stromal elements and cellular debris. The resulting cell suspension will be incubated with 4.5 µm magnetic beads coated with MOC31 antibody, and simultaneously with different nonmagnetic, fluorescent microparticles coated with either anti-Her2, anti-CD44, or anti-Muc1 by flow-cytometry.
Results: 62 cases from 2009.1 to 2009.9 in our hospital has been studied, and results as follows: 1. Immunomagnetic evaluation of alive tumor cells in SLNs is rapidly and easily performed using the MOC-31 antibody that binds to the vast majority of breast cancer cells. The novel technologies will demonstrate higher detection sensitivity (96%) and lower false negative rate (4.0%). 2. For the intraoperative frozen HE staining, the sensitivity was 68%, false negative rate was 32%; and for CK-IHC, the sensitivity was 76.0%, and the false negative rate was 24%. 3.To compare to standard intraoperative procedures and histopathologic techniques of analyzing the SLN to that of the novel approach, it could get higher sensitivity (96%vs 68%,P=0.023;96%vs76%,P=0.049), lower false negative rate (4%vs32% ,P=0.023;4%vs24%,P=0.049) and higher micrometastasis detection rate. 4.Expession of Her2,CD44 and Muc1 in SLN is 32.5%±2.2%,83.4± 4.1% and 86.6%±3.4%, and each has positively correlated with the expression of that in primary tumor (P&lt;0.5).
Conclusion: Our novel approach that utilizing immunobead detection of metastatic breast cancer cells, and simultaneously characterize the isolated cells for membrane markers coated with antibodies targeting Her2, Muc1 or CD44 by flow-cytometry, has rapid speed and high accuracy. Compared to traditional HE and CK-IHC, it has higher sensitivity and lower false negative rate, and could be used more widely and easily. Expression of CD44, Her2 and Muc1 in sentinel lymph nodes were positively correlated with the expression of those in primary tumor. It is suggested that the three biomarkers above could predict metastasis of sentinel lymph nodes, and maybe direct treatment after operation.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-01-17.
Abstract P1-01-21: Predicting Risk of Axillary Lymph Node Metastasis: A Novel, Decision Tree-Based Approach That Can Handle Incomplete Datasets
Authors: Takada M , Sugimoto M , Naito Y , Kondo M , Kuroi K , Inamoto T , Tomita M , Toi M. 
Published: April 2011

Abstract
Background: Although axillary lymph node (AxLN) status, the most important prognostic factor in primary breast cancer patients, is used to tailor systemic therapy, precise staging of AxLN status before primary systemic therapy remains difficult. Sophisticated computational tools, especially nomograms, are used to predict the AxLN status. However, their prediction ability is limited by the requirement for datasets without any defects and their ability to deal with only a limited number of features. The aim of this study was to develop a novel mathematical algorithm to predict the AxLN status that can handle datasets with a large number of features containing missing values as are frequently observed in clinical datasets.
Methods: Pathological-, physical-, and diagnostic-image features (mammography and ultrasonography) from patients with primary invasive breast cancer who initially underwent sentinel lymph node biopsy or had undergone axillary lymph node dissection were used for training (n=168). Data resampling, feature-selection based on a support vector machine, an alternative decision tree (ADTree), and data ensemble methods were integrated to predict AxLN metastasis from the large number of clinicopathological variables. Even in the absence of data points, the ADTree method can be used to calculate a certain range of classification probabilities. After development of the prediction model, we validated the model using an independent validation dataset (n=56). Results: The developed model contained 14 variables and exhibited high accuracy; the area under the receiver operating characteristics curve was 0.89 (95% CI, 0.84 — 0.94) and 0.86 (95% CI, 0.76 — 0.95) for the training-and validation dataset, respectively. Bootstrap analyses yielded 0.90 ± 0.026 for training and 0.85 ± 0.053 for validation; the missing value replacement test showed 0.86 ± 0.011 for training and 0.83 ± 0.020 for validation.
Conclusions: The model permitted the accurate prediction of AxLN metastasis even in datasets with missing values. Furthermore, it incorporates a combination of clinicopathological variables that can be obtained non-invasively for their prediction. Thus, it may become a valuable tool for the development of treatment strategies.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-01-21.
Abstract P1-01-24: Is the Dye Method Alone Useful for Sentinel Lymph Node Biopsy in Early-Stage Breast Cancer? Prospective Analysis of 1081 Patients after SLN Biopsy
Authors: Iwase T , Nakamura R , Naohito Y , Kouya F , Toshi O , Miyazaki M. 
Published: April 2011

Abstract
Introduction: Sentinel lymph node biopsy (SLNB) for breast cancer has been established. The objective of this study was to investigate factors which elevate the identification rate employing the dye method (DYm) alone.
Subjects: The subjects were 1,081 cN0 breast cancer patients who underwent preoperative cytology of the axillary lymph nodes at our facility between May 2001 and April 2010.
Methods: In the morning of the operation day, 0.3 ml of technetium phytate was subcutaneously injected immediately above the tumor, and 5 ml of indigocarmine was subcutaneously injected into the para-areolar region on the axillary side immediately before surgery, attempting to identify sentinel lymph nodes (SLN) using the combination method. The rates of identification employing the DYm and RI method (Rim) and false-negative rates were calculated. Regarding SLN in which the highest count was detected by the RIm as the first SLN (fSLN), consistency with that detected using the DYm was investigated.
Results: The mean numbers of SLN identified by the DYm and RIm were 1.36 and 1.90, respectively, showing that significantly more lesions were identified employing the RIm (P&lt;0.05). The identification rates employing the dye, RI, and both methods were 88.7, 98.7, and 99.3%, respectively, and the consistency of fSLN between the DYm and RIm was 78.1%. SLN metastasis detected using the RIm could not be identified employing the dye method in 20 cases. The age, tumor size, and BMI were investigated in these 20 cases, and a significant difference was noted in the tumor size. Conclusion: The identification rate employing the DYm alone was lower than that employing the RIm. The consistency of fSLN between the two methods was 78.1%. Although the RIm may have biopsied excess lymph nodes (LN), its use may be important to complement the DYm. Dye does not readily enter metastatic LN because of the presence of tumor plugs. The application of preoperative axillary LN cytology to cases with large tumors to exclude metastasis-positive cases may elevate the SLN identification rate employing the DYm.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-01-24.
Abstract P1-01-28: Utility of 18F-Fluoro-Deoxyglucose Emisión Tomography/Computed and Sentinel Node Biopsy for Axillary Staging in Primary Breast Cancer. Roffo PET/CT 1 Trial
Authors: Noblia CM , Cresta Morgado CE , Azar ME , Bruno G , Gonzalez C , Parma P , Gonzalez EG , Armanasco E , Montoya D , Ipiña JM , Zarlenga C , Gorostidi S. 
Published: April 2011

Abstract
Objetive 1. - To compare the capacity of the PET and the sentinel node for the detection of axillary metastasis (MTS). 2. - To evaluate sensitivity, specificity, positive and negative predictive value of the PET/CT. Inclusion criteria-Breast cancer T1 T2 NO. Palpable nodes suspicious of involvement. Exclusion criteria-Ductal carcinoma in situ, inflammatory carcinoma, recent biopsy of the breast, pregnancy or lactation, diabetes. Method 18-FDG PET/CT was made 15 days before the surgery. The sentinel node biopsy took place with the combined method (radioisotopes and patent blue)
Material They were evaluated 54 patients. Age average: 59 years (37-79). T1: 36 patients (67%); T2: 18 patients (33%) Tumor size between 5 and 40 mm (average 19) clinically negative axilla 46 (85%); doubtful axilla 8 (15%). Stage I: 33 patients (61%); stage II: 21 patients (39%). Results Forty four (81%) of the tumors were invasive ductal carcinoma: 7 (13%) invasive lobular carcinoma; and 3 (6%) ductolobular. Fifteen patients had MTS in the SN (28%), of these 3 were micrometastasis. In 2 patients the PET/CT changed the stage since it was positive for bony and pulmonary MTS.
Results PET in breast: Eleven negatives (FN: 20%). Four were invasive lobular carcinomas; 4 were T1a. Sensitivity 80%. VPP = 100%. False negative: 20%Result PET in axila: In 45 patients the PET was negative (83%). Six of them presented MTS in the sentinel node; 3 of them were micrometastasis. False negative: 40%. Sensitivity: 60%.VPN 87%. In 9 patients the PET were positive (17%) and the sentinel node was positive in all the cases. Specifity: 100%. VPP = 100%. In 8 patients the axilla was doubtful, of these only in one patient PET and the SN was positive. Conclusion 1.-PET/CT does not contribute advantages for the axillary staging in the initial stage because it does not manage to identify smaller MTS of 5 mm. 2.- A negative PET/CT does not replace the sentinel node biopsy. 3.- A positive PET/CT would indicate the necessity of making an axillary dissection still in clinically negative axilla. 4- In clinically doubtful axilla was coincidence between PET/CT and the SN as much in the negatives as in the positives.
Key words: Occult axillary metastases. Positron emission tomography. Sentinel node biopsy.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-01-28.
Abstract P1-01-30: True Sentinel Nodes Identified by CT-Lymphography Accurately Stage the Axilla in Patients with Breast Cancer: Removal of True Sentinel Nodes Alone Is Sufficient
Authors: Motomura K , Ishitobi M , Komoike Y , Koyama H , Inaji H , Horinouchi T , Nakanishi K. 
Published: April 2011

Abstract
Background: Sentinel node biopsy (SNB) using dye and/or radioisotope often results in the identification and removal of multiple nodes as sentinel nodes (SN), although most of these nodes may be non-SN. CT-lymphography (CT-LG) can distinguish true SN from non-SN because of the visualization of the lymphatic channel. This study investigated whether true SN identified by CT-LG accurately stage the axilla in patients with breast cancer, making it sufficient to remove true SN alone.
Methods: This study included 168 patients with breast cancer with clinically negative nodes. Contrast agent was injected intradermally into the skin overlying the breast tumor and in the subareolar region. True SN were identified by CT-LG. Marking the location of true SN was performed on the skin surface using a CT laser light navigator system. SNB was performed using a combination of dye and radioisotope. Lymph nodes located just under the marking were first removed as true SN. Then, all dyed nodes or all hot nodes were removed.
Results: The mean number of true SN identified by CT-LG was 1.1 (range 1-3). The mean number of hot and/or dyed nodes removed was 1.8 (range 1-6). One hundred forty-seven patients (87.5%) had 1 true SN removed, 19 (11.3%) had 2 true SN removed, and 2 patients (1.2%) had 3 true SN removed. Twenty-one (12.5%) patients had ≥2 true SN removed, whereas 91 (54.2%) of patients had ≥2 hot and/or dyed nodes removed (P&lt;0.0001). Pathologic evaluation demonstrated that 38 (22.6%) of 168 patients had metastasis to at least one node. All of these 38 patients demonstrated metastases to at least one of the true SN identified by CT-LG. There were no adverse events associated with CT-LG.
Conclusions: True SN identified by CT-LG accurately staged the axilla in patients with breast cancer. Removal of true SN alone may reduce the postoperative morbidity and cost of the procedure by decreasing the surgical duration as well as the cost of pathologic analysis.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-01-30.
Abstract P1-02-02: Processing of GPNMB by ADAM-10 in Breast Tumors Releases an Extracellular Domain with Angiogenic Properties
Authors: Rose AAN , Annis MG , Dong Z , Pepin F , Hallett M , Park M , Siegel P. 
Published: April 2011

Abstract
Background: Glycoprotein non-metastatic B (GPNMB), also known as Osteoactivin, is a cell surface bound, transmembrane protein that is expressed in 41-74% of breast cancers. We have shown that it promotes migration, invasion and metastasis of breast cancer cells, that it is associated with shorter recurrence-free and overall survival times, and that it is most commonly expressed among breast tumors of the basal/triple-negative subtypes. Patients with basal/triple-negative breast cancer have aggressive disease and are not amenable to currently available targeted therapies. For these reasons GPNMB is an attractive target for therapeutic intervention in breast cancer; indeed, a GPNMB-targeted antibody-drug conjugate (CDX-011) has shown impressive clinical response among patients with GPNMB-positive breast cancer and is being investigated in Phase IIb clinical trials. Despite its promise as a therapeutic target in breast cancer, little is known about the functional role of GPNMB the primary tumor microenvironment.
Materials and Methods: We have employed 66cl4 murine mammary carcinoma cells and human BT549 breast cancer cells to investigate the effects of GPNMB on tumor growth and angiogenesis, respectively in vivo. Control and GPNMB-expressing tumors were analyzed using immunohistochemistry for degree of proliferation apoptosis and angiogenesis. To better characterize functionally important domains of GPNMB we employed immunoblot and ELISA analyses to assess levels of full length, intact GPNMB and shed GPNMB ectodomain in breast cancer cells. Transient siRNA-mediated knockdown studies were used to identify sheddases responsible for GPNMB shedding. Finally, we employed in vitro migration assays to assess function of the shed extracellular domain (ECD) of GPNMB.
Results: In this study we show that GPNMB promotes the outgrowth of mammary tumors in vivo and enhances their microvascular density. In an effort to investigate the functional domains of GPNMB that are responsible for this pro-angiogenic effect, we found that that the extracellular domain (ECD) of GPNMB is constitutively shed in breast cancer cells and show that this ECD is capable of inducing endothelial migration. Finally, we have implicated a disintegrin and metalloprotease-10 (ADAM10) as a novel sheddase responsible for liberation GPNMB ectodomain.
Conclusion: In this study we have described ADAM10-mediated shedding of GPNMB ECD - a protein fragment that induces endothelial cell migration - as a novel mechanism by which GPNMB can promote angiogenesis in breast cancer. Further efforts to characterize the effect of GPNMB on endothelial cell function will be discussed.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-02-02.
Abstract P1-02-03: JAM-2, Junctional Adhesion Molecule-2 Influences the Adhesion and Migration of Vascular Endothelial Cell
Authors: Al-Mrabt N , Martin TA , Jiang WG 
Published: April 2011

Abstract
Background. Junctional Adhesion Molecule (JAM)-2, is a protein that belong to the JAM Ig superfamily. JAM-2 is primarily found in vascular endothelial and epithelial cells and considered key to the making of the brain blood barrier (BBB). JAM-2 is located in the tight junction region in the cells and, via the homotypic interactions, regulates the rolling and adhesion of lymphocytes, NK cells, dendritic cells and platelets over the endothelium lining in the blood stream. It has also been indicated to possibly influence the rolling of tumours cells over endothelial cells. Little is known with regard to the biological influence of JAM-2 on endothelial cells. In the present study, we investigated the impact of JAM-2 on the biological behaviour of vascular endothelial cells. Materials and methods. Human vascular endothelia cell, HECV was used. Anti-JAM-2 ribozyme transgenes were constructed based on the secondary structure of human JAM-2 and were used to transfect HECV cells in order to knock down the expression of JAM-2 in the cells. The attachment of the cells to matrix surface and the cellular migration were determined using a Electric Cell-substrate Impedance Sensing (ECIS) method. The tight junction function, trans-endothelial electric resistance (TER) was evaluated using a two chamber cell model with an EVOM voltammeter. In vitro tubule forming was assessed using a sandwich tubule forming assay. Results. The Vascular endothelial cell, HECV, expressed JAM-2 in its wild type as shown by RT-PCR. We created JAM-2 knockdown sublines, HECVΔJAM2, by way of ribozyme transgenes. Knocking down JAM-2 resulted in a rapid rise of cell adhesion (297.7±8.4 in control cells, P&lt;0.0001 vs 364.9±19.7 in ohm vs HECVΔJAM2 cells, at 4000Hz), over a 2 hour period. Likewise, HECVΔJAM2 cells displayed a rapid rise in cellular migration when compared with control cells. This was observed over a wide frequencies (250-10,000Hz) (1046.5±8.9 for control cells and 1139.4±24.0 for HECVΔJAM2 cells at 250Hz, P&lt;0.001).It is interesting to note that there was no significant difference in TER in control cells and HECVΔJAM2 (p=0.116). In the tubule forming assay, it was demonstrated that HECVΔJAM2 formed less tubules in comparison with control cells, although this is not statistically significant (p=0.061), Conclusion. JAM-2 has a profound impact on the adhesion and cellular migration of endothelial cells. It also influences the transendothelial resistance and tubule forming of the cell, although to a lesser content. Together with the knowledge on its role in lymphocyte/tumour-endothelial interaction, JAM-2 may have a role in the extravasation process of cancer cells.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-02-03.