bluuebunny/crossref_metadata_2025 huggingface dataset:
Endothelin-1 attenuates increases in hydraulic conductivity due to platelet-activating factor via prostacyclin release
Authors: Cureton Elizabeth L. , Strumwasser Aaron , Kwan Rita O. , Dozier Kristopher C. , Curran Brian , Sadjadi Javid , Victorino Gregory P.
Published: December 2010

We previously showed that endothelin-1 (ET-1) and prostacyclin (PGI2) similarly attenuate increases in microvascular permeability induced by platelet-activating factor (PAF). This led us to hypothesize that ET-1 attenuates trans-endothelial fluid flux during PAF through PGI2release. We tested this hypothesis in three phases. First, bovine pulmonary artery endothelial cells were exposed to 0.008–8 μM ET-1 and assayed for PGI2release. Second, to determine whether increased transmonolayer flux after PAF could be attenuated by ET-1 or PGI2and reversed by PGI2synthesis inhibition or PGI2receptor blockade, we measured endothelial cell transmonolayer flux after cells were exposed to 10 nM PAF plus 10 μM PGI2or 80 pM ET-1, with or without 500 μM tranylcypromine (PGI2synthase inhibitor) or 20 μM CAY-10441 (PGI2receptor blocker). Finally, hydraulic conductivity (Lp) was measured in rat mesenteric venules in vivo after exposure to 10 nM PAF and 80 pM ET-1 with or without tranylcypromine (100 and 500 μM) or CAY-10441 (2 and 20 μM). We found that in vitro, ET-1 stimulated a dose-dependent increase in PGI2production (from 126 to 217 pg/ml, P < 0.01). Compared with PAF alone, PGI2plus PAF and ET-1 plus PAF decreased transmonolayer flux similarly by 52 and 46%, respectively ( P < 0.01), while tranylcypromine and CAY-10441 reversed these effects by 92 and 47%, respectively ( P < 0.05). In vivo, PAF increased Lpfourfold ( P < 0.01) and ET-1 attenuated this effect by 83% ( P < 0.01). Tranylcypromine and CAY-10441 reversed the ET-1 attenuation in Lpduring PAF by 55 and 45%, respectively ( P < 0.01). We conclude that ET-1 may stimulate endothelial cell PGI2release to attenuate the increases in transmonolayer flux and hydraulic conductivity secondary to PAF.
Associations between sports participation, cardiorespiratory fitness, and adiposity in young adult twins
Authors: Mustelin L. , Latvala A. , Pietiläinen K. H. , Piirilä P. , Sovijärvi A. R. , Kujala U. M. , Rissanen A. , Kaprio J.
Published: December 2010

Exercise behavior, cardiorespiratory fitness, and obesity are strongly influenced by genetic factors. By studying young adult twins, we examined to what extent these interrelated traits have shared genetic and environmental etiologies. We studied 304 twin individuals selected from the population-based FinnTwin16 study. Physical activity was assessed with the Baecke questionnaire, yielding three indexes: sport index, leisure-time index, and work index. In this study, we focused on sport index, which describes sports participation. Body composition was determined using dual-energy X-ray absorptiometry and cardiorespiratory fitness using a bicycle ergometer exercise test with gas exchange analysis. The Baecke sport index was associated with high maximal oxygen uptake adjusted for lean body mass (V̇o2max[adj]) ( r = 0.40), with low body fat percentage (BF%) ( r = −0.44) and low waist circumference (WC) ( r = −0.29). Heritability estimates for the key traits were as follows: 56% for sport index, 71% for V̇o2max[adj], 77% for body mass index, 66% for WC, and 68% for BF%. The association between sport index and V̇o2max was mostly explained by genetic factors (70%), as were both the association between sport index and BF% (71%) and that between sport index and WC (59%). Our results suggest that genetic factors explain a considerable part of the associations between sports participation, cardiorespiratory fitness, and obesity.
Peroxisome Biogenesis: Something Old, Something New, Something Borrowed
Authors: Mast Fred D. , Fagarasanu Andrei , Knoblach Barbara , Rachubinski Richard A.
Published: December 2010

Eukaryotic cells are characterized by their varied complement of organelles. One set of membrane-bound, usually spherical compartments are commonly grouped together under the term peroxisomes. Peroxisomes function in regulating the synthesis and availability of many diverse lipids by harnessing the power of oxidative reactions and contribute to a number of metabolic processes essential for cellular differentiation and organismal development.
TMEM16A Protein: A New Identity for Ca2+-Dependent Cl− Channels
Authors: Ferrera Loretta , Caputo Antonella , Galietta Luis J. V.
Published: December 2010

Ca+-dependent Cl− channels (CaCCs) play a variety of physiological roles in different organs and tissues, including transepithelial Cl− secretion, smooth muscle contraction, regulation of neuronal excitability, and transduction of sensory stimuli. The recent identification of TMEM16A protein as an important component of CaCCs should allow a better understanding of their physiological role, structure-function relationship, and regulatory mechanisms.
Long‐Term Followup of Dermal Substitution with Acellular Dermal Implant in Burns and Postburn Scar Corrections
Authors: Juhasz I. , Kiss B. , Lukacs L. , Erdei I. , Peter Z. , Remenyik E.
Published: December 2010

Full‐thickness burn and other types of deep skin loss will result in scar formation. For at least partial replacement of the lost dermal layer, there are several options to use biotechnologically derived extracellular matrix components or tissue scaffolds of cadaver skin origin. In a survey, we have collected data on 18 pts who have previously received acellular dermal implant Alloderm. The age of these patients at the injury varied between 16 months and 84 years. The average area of the implants was 185 cm2. Among those, 15 implant sites of 14 patients were assessed at an average of 50 months after surgery. The scar function was assessed by using the modified Vancouver Scar Scale. We have found that the overall scar quality and function was significantly better over the implanted areas than over the surrounding skin. Also these areas received a better score for scar height and pliability. Our findings suggest that acellular dermal implants are especially useful tools in the treatment of full‐thickness burns as well as postburn scar contractures.
Xenobiotic Exposure and Autoimmune Hepatitis
Authors: Gilbert Kathleen M.
Published: December 2010

Although genetics contributes to the development of autoimmune diseases, it is clear that “environmental” factors are also required. These factors are thought to encompass exposure to certain drugs and environmental pollutants. This paper examines the mechanisms that normally maintain immune unresponsiveness in the liver and discusses how exposure to certain xenobiotics such as trichloroethylene may disrupt those mechanisms and promote autoimmune hepatitis.
A Note on Improved Homotopy Analysis Method for Solving the Jeffery‐Hamel Flow
Authors: Motsa Sandile Sydney , Sibanda Precious , Marewo Gerald T. , Shateyi Stanford
Published: December 2010

This paper presents the solution of the nonlinear equation that governs the flow of a viscous, incompressible fluid between two converging‐diverging rigid walls using an improved homotopy
analysis method. The results obtained by this new technique show that the improved homotopy
analysis method converges much faster than both the homotopy analysis method and the optimal
homotopy asymptotic method. This improved technique is observed to be much more accurate
than these traditional homotopy methods.
Using the Response Surface Method to Optimize the Turning Process of AISI 12L14 Steel
Authors: Kandananond Karin
Published: December 2010

The purpose of this paper is to determine the optimal cutting conditions for surface roughness in a turning process. This process is performed in the final assembly department at a manufacturing company that supplies fluid dynamic bearing (FDB) spindle motors for hard disk drives (HDDs). The workpieces used were the sleeves of FDB motors made of ferritic stainless steel, grade AISI 12L14. The optimized settings of key machining factors, depth of cut, spindle speed, and feed rate on the surface roughness of the sleeve were determined using the response surface methodology (RSM). The results indicate that the surface roughness is minimized when the depth of cut is set to the lowest level, while the spindle speed and feed rate are set to the highest levels. Even though the results from this paper are process specific, the methodology deployed can be readily applied to different turning processes.
Extranodal Natural-Killer/T-Cell Lymphoma, Nasal Type
Authors: Gill Harinder , Liang Raymond H. S. , Tse Eric
Published: December 2010

The World Health Organization (WHO) classification recognizes 2 main categories of natural killer (NK) cell-derived neoplasms, namely, extranodal NK/T-cell lymphoma, nasal type, and aggressive NK-cell leukaemia. Extranodal nasal NK/T-cell lymphoma is more frequent in the Far East and Latin America. Histopathological and immunophenotypical hallmarks include angiocentricity, angiodestruction, expression of cytoplasmic CD3 epsilon (ε), CD56, and cytotoxic molecules and evidence of Epstein-Barr virus (EBV) infection. Early stage disease, in particular for localized lesion in the nasal region, is treated with chemotherapy and involved-field radiotherapy. On the other hand, multiagent chemotherapy is the mainstay of treatment for advanced or disseminated disease. L-asparaginase-containing regimens have shown promise in treating this condition. The role of autologous hematopoietic stem cell transplantation is yet to be clearly defined. Allogeneic hematopoietic stem cell transplantation, with the putative graft-versus-lymphoma effect, offers a potentially curative option in patients with advanced disease.
Contractions of Product Density Operators of Systems of Identical Fermions and Bosons
Authors: Radzki Wiktor
Published: December 2010

Recurrence and explicit formulae for contractions (partial traces)
of antisymmetric and symmetric products of identical trace class operators
are derived. Contractions of product density operators of systems of identical
fermions and bosons are proved to be asymptotically equivalent to, respectively,
antisymmetric and symmetric products of density operators of a single
particle, multiplied by a normalization integer. The asymptotic equivalence
relation is defined in terms of the thermodynamic limit of expectation values
of observables in the states represented by given density operators. For
some weaker relation of asymptotic equivalence, concerning the thermodynamic
limit of expectation values of product observables, normalized antisymmetric
and symmetric products of density operators of a single particle are
shown to be equivalent to tensor products of density operators of a single
particle.
Undergraduates' Criteria to Justify Claims Proposed after Laboratory Experiments
Authors: Lin Jer-Yann , Guo Ding-Ying
Published: December 2010

This study investigates the criteria undergraduates adopt to justify their claims proposed after laboratory experiments. There are two categories of justifications in the current literature,empirical consistencyandplausibility of claims, but observations of college juniors in the laboratory demonstrated the need for a third category,observation reliability. This assumption was further tested by analyzing the warrants undergraduates wrote to justify their claims formed after laboratory experiments. Three students' justification criteria were identified, that is,empirical consistency,plausibility of claims, andobservation reliability. The most frequently used criterion isplausibility of claimsto justifygood results, while that isobservation reliabilityto justifybad results. Moreover, multiple justification, which means more than one attempt being made to justify a given claim, was also found. It reveals that multiple justification, rather than single justification, is suitable for students to make scientifically acceptable claims. The implications and suggestions of this study are also discussed.
Involvement of the Soluble Urokinase Receptor in Chondrosarcoma Cell Mobilization
Authors: Bifulco Katia , Longanesi-Cattani Immacolata , Masucci Maria Teresa , De Chiara Annarosaria , Fazioli Flavio , Di Carluccio Gioconda , Pirozzi Giuseppe , Gallo Michele , La Rocca Antonello , Apice Gaetano , Rocco Gaetano , Carriero Maria Vincenza
Published: December 2010

High levels of urokinase receptor (uPAR) in tissue and serum of patients with chondrosarcoma correlate with poor prognosis. First, we analyzed the uPAR levels in tissues and plasma of five patients affected by chondrosarcoma. Interestingly, very high levels of uPAR and its soluble forms (SuPAR) were found on tumor cell surfaces and plasma, respectively, of two patients with lung metastases. Therefore, to investigate the role of SuPAR in chondrosaromas, we generated a primary cell culture from a chondrosarcoma tissue overexpressing uPAR on cell surfaces. We found that chondrosarcoma-like primary culture cells release a large amount of SuPAR in the medium.In vitro, SuPAR elicits chondrosarcoma cell migration likely through its uPAR88-92sequence, since the DII88-183or DIIDIIR88-284uPAR domains retain motogen effect whereas DI1-87or DIII184-284domains, both lacking the uPAR88-92sequence, are ineffective. Chondrosarcoma cells cross matrigel in response to SuPAR, and their invasion capability is abrogated by RERF peptide which inhibits uPAR88-92signalling. These findings assign a role to uPAR in mobilizing chondrosarcoma cells and suggest that RERF peptide may be regarded as a prototype to generate new therapeutics for the chondrosarcoma treatment.
SENTinel Node Biopsy before or after NeoAdjuvant Systemic Treatment – The German SENTINA Trial.
Authors: Kuehn T. , Bauerfeind I. , Fehm T. , Fleige B. , Helms G. , Liedtke C. , Mai M. , von Minckwitz G. , Staebler A. , Untch M.
Published: December 2010

Background: For patients with breast cancer undergoing neoadjuvant systemic treatment (NST) the optimal timing of sentinel node biopsy (SLNB) is unclear. While adequate axillary staging prior to NST could allow for a-priori tailoring of systemic treatment, SLNB after NST could spare those patients from complete axillary dissection (AD), who are free of metastases in the axilla or convert from a positive (Npos) to a negative (Nneg) axillary status following NST. For these patients, however, the reliability of SLNB to predict the axillary status remains yet to be prospectively confirmed.Material and Methods: The German SENTINA protocol, as a substudy of the German Geparquinto neoadjuvant trial of the AGO and the German Breast Group (GBG), is a 4-arm prospective multicenter case control study designed to examine the role of SLN in patients undergoing NST.Study design:Arm A before NST: clinically Nneg + negative SLN --> no add. Axillary surgery Arm B before NST: clinically Nneg + positive SLN --> sentinel-node-guided AD after NST Arm C before NST: clinically Npos, after NST: clinically Nneg --> sentinel-node-guided AD after NST Arm D before NST: clinically Npos, after NST: clinically Npos --> ADStudy objectives:1. to compare the detection rate of SLNB before and after NST2. to evaluate the number of patients with involved nodes despite being clinically Nneg before NST3. to determine the number of patients who convert from clinically Npos to histologically Nneg after NST4. to evaluate the false-negative rate of SNB for patients who convert from clinically Npos to histologically SNneg after NST5. to determine lymphatic pathway configuration, detection rate and false-negative rate of SLNB after prior SLNB6. to determine the false negative rate of intraoperative frozen section before and after NSTResults: Until now 366 patients from 30 institutions have been enrolled in this trial. 230 patients have completed primary systemic and surgical treatment. A total of 1508 patients were calculated as adequate to have the one-sided confidence interval of 95 % for the false negative rate of SLNB in the arms B and C not exceeding 10% (196 pts each). 82 pts entered arm A. Fifty-eight, 76 and 24 pts were recruited for the arms B, C and D respectively.Conclusion: To our knowledge the SENTINA trial is the first prospective multicenter study to evaluate the role of SLNB in the neoadjuvant setting. The SENTINA protocol will allow for a direct comparison of the feasibility and reproducibility of a standardized SLNB-procedure before and after NST. The study will provide reliable data on the predictive value of SLNB before and after NST in patients converting from a clinically positive to a negative axillary status and offer insights into the biology of axillary response to NST.

Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1008.
Evaluation of the Predictive Performance and Regimen Specificity of a 30-Gene Predictor of Pathologic Complete Response in a Prospective Randomized Neoadjuvant Clinical Trial for Stage I-III Breast Cancer.
Authors: Tabchy A. , Symmans W. , Valero V. , Vidaurre T. , Lluch A. , Qi Y. , Souchon E. , Barajas-Figueroa L. , Gomez H. , Martin M. , Coutant C. , Hess K. , Hortobagyi G. , Pusztai L.
Published: December 2010

Purpose: To prospectively evaluate in a randomized trial if a previously reported multigene predictor of pathologic complete response (pCR) to preoperative weekly paclitaxel and fluorouracil-doxorubicin-cyclophosphamide (T/FAC) chemotherapy can accurately predict pCR to neoadjuvant T/FAC chemotherapy, and if it also predicts pCR to FAC only chemotherapy. Furthermore, it is unknown if the T/FAC regimen is superior to 6 courses of FAC; therefore we compare the pCR rates for patients who receive T/FAC versus FACx6 preoperative chemotherapy.Materials and Methods: Patients with stage I-III breast cancer (n=273) were randomly assigned to receive either 12 courses of weekly paclitaxel followed by 4 courses of FAC (T/FAC, n=138), or 6 courses of FAC (FACx6, n=135) neoadjuvant chemotherapy. All patients underwent a pretreatment FNA biopsy of the tumor for gene expression profiling on oligonucleotide microarrays, and treatment response prediction (pCR versus residual disease, RD) was performed using the multigene predictor. Predicted and observed pathologic responses were compared independently in the two treatment arms.Results: The pCR rate was 19% with T/FAC and 9% with FACx6 (p<0.05). In the T/FAC arm, the positive predictive value (PPV) of the genomic predictor was 38% (95%CI:21-56%), the negative predictive value (NPV) 88% (CI:77-95%), sensitivity 63% (CI:38-84%), specificity 72% (CI:60-82%), and the AUC 0.711. In the FAC only treatment arm, the PPV was 9% (CI:1-29%), the NPV 92% (CI:83-97%), sensitivity 29% (CI:4-71%), specificity 75% (CI:64-84%), and the AUC 0.584. This suggests that the genomic predictor is regimen-specific. In a multivariate analysis including age, tumor size, nodal status, histologic grade, HER2 and estrogen receptor (ER) status and the genomic predictor, only ER status was a significant predictor of pCR.Discussion: Pathologic complete response rate was significantly higher in the T/FAC arm compared to the FACx6 arm indicating a higher efficacy of the paclitaxel containing arm. Patients who were predicted to achieve pCR to T/FAC had a significantly higher pCR rate (38%) than unselected patients (19%) or patients predicted to have RD (12%) when treated with this regimen. These results confirm that the multigene predictor can identify patients with greater than average sensitivity to T/FAC chemotherapy.

Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 101.
Pre-Operative Axillary Nodal Staging by Ultrasonography and Fine-Needle Cytology Reduces the Number of Unnecessary Sentinel Node Biopsies in Breast Cancer Patients.
Authors: Baruah B. , Goyal A. , Young P. , Douglas-Jones A. , Mansel R. , on Behalf of Cardiff Breast Unit .
Published: December 2010

Aims: The role of pre-operative axillary ultrasound for nodal staging in early breast cancer patients is evolving. In this study, we evaluated the role of axillary ultrasound (AUS) and fine-needle aspiration cytology (FNAC) to stage the axilla pre-operatively in a large series of operable breast cancer patients including its role in the detection of nodal micrometastases. A second objective was to ascertain whether a significant learning curve is associated with this technique.Methods: Between October 2006 and March 2009, all patients diagnosed with invasive breast cancer in our unit had an AUS pre-operatively. Patients with suspicious nodes on ultrasound underwent FNAC. Cytology positive patients proceeded directly to axillary clearance, while others underwent sentinel lymph node biopsy. Data from this retrospective study was analyzed using appropriate statistical techniques to evaluate the efficacy of this technique to detect nodal metastases pre-operatively.Results: 495 patients scheduled to undergo surgery for invasive breast cancer were included in this study. 7 patients had bilateral malignancies and, therefore, a total of 502 axillae were examined using ultrasound. The median age of patients in our study was 61 years (range 32-91). 137 patients (27.3%) had proven nodal metastases on final histology. 39 of 137 (28.5%) node positive patients were accurately identified by pre-operative AUS and FNAC and, therefore, spared an unnecessary sentinel node biopsy. The combined technique of AUS and FNAC had an overall accuracy of 80.5% (95% CI: 76.8-83.7), sensitivity of 28.5% (95% CI: 21.6-36.5), specificity of 100% (95% CI: 99-100), positive predictive value of 100% (95% CI: 91-100), and negative predictive value of 78.8% (95% CI: 74.9-82.3). Pre-operative AUS and FNAC was normal in all patients with nodal micrometastases (n=15) and isolated tumour cells (n=11) on histopathology. No significant learning curve was demonstrated for this technique in our study. Overall, 28.5% of node positive patients and 7.9% of all breast cancer patients avoided an unnecessary sentinel node biopsy due to this procedure.Conclusions: Pre-operative AUS and FNAC is an inexpensive, minimally-invasive outpatient procedure with an accuracy of more than 80% that can avoid unnecessary sentinel lymph node biopsy in 28.7% of node positive patients. It has no role in the detection of nodal micrometastases and there is no demonstrable learning curve seen with this technique.

Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1018.
Can We Skip Sentinel Lymph Node Biopsy in Patients Who Have Microinvasive Breast Cancer?
Authors: Ko B. , Seo J. , Kwon S. , Lee Y. , Lim W. , Lee J. , Kim H. , Jang M. , Ku B. , Son B. , Ahn S.
Published: December 2010

Background: Sentinel lymph node(SLN) biopsy in patients with ductal carcinoma in situ(DCIS) was controversial. We may skip SLN biopsy when we performed conserving operation with small sized DCIS. But sometimes we can find DCIS with micro-invasive breast cancer (MIC) after operation. Should another operation be performed? We determined the incidence of positive axillary lymph node (ALNs) in patients with MIC, and the predictive factors of ALNs metastasis in these patients. Methods: Between July 1989 and January 2008, 9046 patients had operations performed on invasive breast cancers at Asan Medical Center. From July1989 to February 2003, ALND was performed to surgically stage the axilla. Since May 2003, SNB has been routinely performed for all cases. Patients who were treated with neoadjuvant chemotherapy and those who had no identifiable ALNs at surgery were excluded from the study. We retrospectively checked clinical and pathologic variables including diagnosis, patient demographics, size of DCIS, grade, multi-focal lesion, hormone receptor status, lymphatic invasion status etc. Results: 265 patients were identified with microinvasive (pathologic stage T1mic) breast cancer. Among these patients, 12 patients didn't have ALN study. 2 patients had bilateral MIC. The research was conducted on the remaining 255 cases. There were 13 cases of ALN metastases identified in this group of patients(5%). Young age (p=0.006), multifocal lesion (p=0.040) and lymphatic invasion (p<0.0001) were predictive factors for ALN metastases. There was no incidence of metastatic ALNs among the old age (≥50) patients of this group. Conclusion: As the incidence of ALN metastases in MIC patients is very small, particularly in those who had no lymphatic invasion, single lesion and among old age patients. So we think conservative treatment is one of the available options for these patients. However, due to the size of the subject group in this study, it needs to be validated through extensive prospective research.

Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1019.
Sentinel Lymph Node Biopsy in Patients Who Have Negative Conversion of Axillary Lymph Node after Neoadjuvant Chemotherapy for Node Positive Breast Cancer.
Authors: Lee S. , Hwang S. , Jeong J. , Kim S. , Son E. , Ryu Y. , Jung W. , Lee H.
Published: December 2010

Background: Sentinel lymph node biopsy (SLNB) after neoadjuvant chemotherapy (NAC) has been currently debatable. It is possible that the tumor response to chemotherapy may alter the lymphatic drainage thus causing lower SLN identification rate and higher false negative rate. Further, the response of NAC can be different in each lymph nodes. It is doubtful whether SLNB can accurately predict axillary lymph node (ALN) status after NAC. The aim of this study to determine the identification rate, the false-negative rate, and the accuracy of SLNB after NAC for node positive breast cancer.Patients and Methods: A prospective study was initiated to evaluate the results of SLNB after NAC. From January 2007 to April 2009, 81 patients with positive axillary lymph nodes enrolled from two institutions after IRB-approved. They received NAC and then evaluated negative conversion of metastatic lymph node with both PET and breast US. All of them underwent ALN dissection after SLNB with subareolar intradermal injection technique using radioisotope. We evaluated the identification rate, false negative rate, accuracy of SLNB according to the response of chemotherapy in axillary lymph nodes (negative conversion group or remaining positive group).Results: Before the NAC, 31 patients had multiple axillary lymph node metastasis and 50 patients had single metastasis. After NAC 44 cases (54.3%) turned into negative node and 37 cases (45.7%) remained positive nodes. Total identification rate was 80.2% (65 of 81), false negative rate was 19.0% (8 of 42) and accuracy was 87.7% (57 of 65). In negative conversion group showed 84.1% (37 of 44) of identification rate, 21.1% (4 of 19) of false negative rate, 89.2% (33 of 37) of accuracy. In remaining positive group revealed 75.7% (28 of 37) of identification rate, 17.4% (4 of 23) of false negative rate, 85.7% (24/28) of accuracy. There was no statistical significant difference of identification rate, false negative rate, accuracy of SLNB among the two group after NAC (p=0.343, p=0.534, p=0.478, respectively).Conclusion: This study showed relatively low detection rate and accuracy, high false-negative rate of SLNB, even if the positive nodes changed to negative node after NAC. Thus sentinel lymph node biopsy after NAC for node positive breast cancer should be cautious. Since this study had small number of negative conversion patients, further larger prospective studies are required for more proper conclusion.

Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1022.
Prospective Evaluation of Pre and Postoperative Lymphoscintigraphy in Axillary Reverse Mapping (ARM) for Breast Cancer Patients.
Authors: Cusumano P. , Gomez P. , Dwelshauvers J. , Lilet H. , Nos C.
Published: December 2010

BackgroundThe sentinel lymph node (SLN) procedure, has been used successfully to detect lymphatic involvement. The expected reduction in morbidity and improvement in the quality of life of patients remains uncertain. In spite of this minimal invasive technique, 40 to 50 % of axilla are explored by classic axillary dissection. The aim of axillary reverse mapping (ARM) is to preserve the main lymphatic chain in relation to lymphatic arm drainage during an axillary dissection, reducing the rate of lymphedema.ObjectivesThe objective of this study is to describe a prospective comparison of pre and post axillary dissection (AD) lymphoscintigraphy, in 15 consecutive breast cancer patients.MethodsIsotope InjectionThe morning of surgery, all patients underwent isotope injection in the ipsilateral hand. Each patients received a single injection of 60 MBq (vol 0.2 ml) into the first interdigital space. The preoperative lymphoscintigraphy was performed 45 min after injection, in surgical position. An average of 2 nodes were visible in the axilla. The postoperative lymphoscintigraphy was planned before starting adjuvant treatment.Surgical TechniqueAfter having performed the lumpectomy or the mastectomy, the surgeon began the AD. The first important step was the identification of the second intercostals brachial nerve. While reserving the nerve, the dissection was carried out from medial to lateral, below the nerve. The gamma probe was then used in order to identify the first radioactive node draining the upper limb. This node was localized in the lateral pillar of the axilla. The ARM nodes were carefully preserved during the dissection with retractors placed over them to protect from inadvertent damage. After completion of AD, the axillary content was examined ex-vivo to identify at least ten nodes within the surgical specimen.ResultsThe mean age is 62.4 years (range 40-81). For all 15 patients, the mean number of axillary nodes removed by means of AD was 10.7 (range 7–14). Of all patients, 3 (87%) had metastatic involvement in the AD with an average of 1.3 (range 1– 2) nodes involved.A lymphoscintigraphic mapping concordance between pre and post, was found in 13 out 15 patients (87%).ConclusionsIsotopic ARM allows identification of radioactive nodes in the axilla in 91% of cases.The very good correlation between pre and postoperative mapping suggests a persistence of the normal LAD, and lets hope for a risk reduction of lymphodema after AD.A longterm follow up is needed to confirm these very promising preliminary results.

Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1025.
A Decision Tree To Predict Four or More Positive Axillary Lymph Nodes in Breast Cancer Patients with Positive Sentinel Node Biopsy: Determining Necessity for Regional Nodal Irradiation in the Absence of Axillary Dissection.
Authors: Macrorie-Fairweather R. , Albuquerque K. , Yao K. , Sinacore J.
Published: December 2010

Background: Regional Nodal Irradiation (RNI) is indicated for breast cancer patients with ≥4 positive axillary lymph nodes (ALN). The need for RNI is unclear for women who don't undergo axillary lymph node dissection (ALND) yet have 1-3 positive sentinel lymph nodes (SLN). In an effort to guide clinician decision-making and potentially spare patients combined toxicities of ALND and radiation, the purpose of this study was to create a decision tree of clinicopathologic variable interactions to predict patients with ≥4 positive ALN.Methods: We reviewed the records of 197 women with breast tumors <5cm and 1-3 positive SLN. After ALND, patients were labeled as having < 4 or ≥ 4 positive ALN. Ten clinicopathologic predictive variables were identified for analysis: patient age, size of tumor, histological type, tumor grade, number of metastatic SLN, largest SLN metastasis size, detection method, estrogen receptor, Ki67 and lymphovascular invasion (LVI). The analysis used Chi-Square Automatic Interaction Detection (CHAID SPSS), a non-parametric, stepwise “regression tree” analysis, with Bonferroni adjusted p-values to create a decision tree.Results: 141 patients had < 4 and 56 had ≥ 4 positive ALN. Three variables were selected into the CHAID tree: LVI, the number of metastatic SLNs, and largest SLN metastasis size. 100% of patients (N=42) had < 4 positive ALN if negative for LVI and had only 1 positive SLN with a metastasis size < 0.2cm (p-value < 0.0432). For patients with LVI (N=77), 13 of 14 (93%) had < 4 positive ALN if the SLN metastasis size was < 0.2cm (p < .0014). The highest prevalence of ≥ 4 positive ALN were patients with LVI and a SLN metastasis size > 0.2cm.Conclusion: The CHAID analysis more accurately predicted patients with < 4 positive ALN compared to those with ≥4. The decision tree provides a new tool for the clinician to determine the necessity for RNI without ALND.

Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1026.
Role of Axillary Ultrasound in Defining Surgical Management of Breast Cancer Patients with Nodal Disease.
Authors: Syed A. , Garbos M. , Patel A. , Bradpiece H. , Stephanie J.
Published: December 2010

Background:With the introduction of Sentinel Lymph Node Biopsy, breast cancer patients with nodal disease have to undergo second surgical axillary procedure. The aim of our study was to correlate the accuracy of ultrasound in redefining surgery in breast cancer patients.Methods:The records of all breast cancer patients who underwent Axillary Lymph Node Dissection (ALND) from January 2008 to December 2008 were reviewed. Of these, patients who had pre operative axillary ultrasound and/or fine needle aspiration cytology were included. All ultrasound were performed by the radiologist with special interest in breast imaging at our breast centre. Comparison of the ultrasound and FNA findings with ALND findings was performed.Results:Seventy Five patients had axillary ultrasound during this period. Twenty five patients (32.3%) had abnormal ultrasound findings. Of these, 22 patients had positive surgical staging and three patients had negative surgical staging. Ten of the abnormal axilla had FNAC done. Of these, seven patients had metastatic cells and all of these patients have finally proven to have positive axillary lymph nodes. Of the fifty patients (67.7%) with normal axilla, 34 patients had negative surgical staging and 16 had positive staging The sensitivity of ultrasound axilla was 57.89%, and specificity was 96%. The positive predictive value was 88% and the negative predictive value was 78.57%Discussion:Ultrasound examination of axilla is a safe and fast method of assessing the lymph nodal status in the preoperative staging of axilla. The results of our study are mostly in agreement with previous published studies. This will reduce the number of patients having to undergo a second axillary procedure, hence saving resources both financially and operating time. It will reduce the number of hospital admissions for the patient; improve cost effectiveness and the patient pathway. We therefore recommend routine axillary ultrasound with FNAC of suspicious/pathological nodes to avoid sentinel node procedure i.e., proceed directly to axillary clearance.

Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1033.
In Which Patients Can We Accurately Evaluate the Status of Axillary Lymph Node Metastases Using Sentinel Lymph Node Biopsy after Neoadjuvant Chemotherapy?
Authors: Yagata H. , Nakamura S. , Tsugawa K. , Yamauchi H. , Nakano E. , Yoshida A. , Mori M. , Kajiura Y. , Onoda T. , Takamoto Y. , Kojima Y. , Kitano A. , In R. , Matsuda N.
Published: December 2010

Background: Several studies have reported on the feasibility of sentinel lymph node (SLN) biopsy after neoadjuvant chemotherapy (NAC) in breast cancer patients. However, the accuracy has been variable depends on reports. We would like to determine in which patients we can accurately evaluate the status of axillary lymph node metastases using SLN biopsy after NAC in cytology-proved positive lymph node patients.Patients and Methods: Ninety-five cytology-proved node positive patients underwent SLN biopsy followed by axillary dissection between February 2007 and April 2009. All of those had clinical response in primary breast tumor detected by MRI after NAC.Results: SLN biopsy after NAC was successfully performed 81 out of 95 patients (85.3%). Among those 81 patients, lymph node metastases after NAC were identified by final pathology in 51 patients (63.0%). Eight of those 51 patients with lymph node metastases showed negative SLN biopsy. Therefore false negative rate was 15.7%. Patients who were diagnosed ER negative from the core needle specimen prior to NAC or had clinical CR by MRI did not showed any false negative by SLN biopsy. SLN were identified in 27 out of those 30 patients (90%). Final pathology after NAC revealed 7 patients with lymph node metastases and all of them had positive SLN. Twenty out of 27 (74.1%) patients revealed no evidence of metastases in both SLN and non-SLN.Discussion: After NAC, the false negative rate of SLN biopsies was high (15.7%) in cytology –proved lymph node-positive breast cancer patients. However, this study suggested that SLN biopsy after NAC may be performed accurately in patients who had ER negative tumor or CR by MRI, and that 20 out of 95 patients (21%) could possibly avoid axillary dissection after NAC. These results need to be confirmed by larger studies for the selected patients.

Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1036.
Sulindac Sulfide Selectively Induces Apoptosis of Human Breast Tumor Cells by Inhibiting PDE5A, Elevating cGMP, and Activating PKG.
Authors: Tinsley H. , Gary B. , Keeton A. , Reynolds R. , Piazza G. , Piazza G.
Published: December 2010

Nonsteroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase (COX)-2 selective inhibitors display promising antineoplastic activity, but the gastrointestinal, renal, and cardiovascular toxicities that result from COX inhibition limit their clinical utility for cancer chemoprevention. Previous studies suggest that the pro-apoptotic activity of these drugs may be due to a COX-independent mechanism involving cyclic guanosine monophosphate (cGMP) phosphodiesterase (PDE) inhibition. However, the specific PDE isozyme(s) responsible has not yet been identified. Here we used the NSAID sulindac sulfide (SS) to further study cGMP PDE as a potential molecular target of the NSAIDs for breast cancer chemoprevention. SS inhibited growth and induced apoptosis of human SK-BR-3 and MDA-MB-231 breast tumor cells, while normal human mammary epithelial cells (HMEC) were less sensitive. SS also inhibited cGMP PDE activity from tumor cell lysates at concentrations comparable to those required for apoptosis, while appreciably higher concentrations were necessary to inhibit activity from HMEC lysates or cAMP PDE activity from any of the cell lysates. Additionally, SS increased intracellular cGMP concentrations and induced protein kinase G (PKG) activity in MDA-MB-231 cells as determined by ELISA and increased levels of phosphorylated VASP, a known PKG substrate, respectively. Moreover, pretreatment with the guanylyl cyclase inhibitor LY83583 desensitized the breast tumor cells to the growth-inhibitory activity of SS, likely by suppressing intracellular cGMP levels. The guanylyl cyclase activator NOR-3 and the cGMP PDE inhibitors MY5445 and trequinsin inhibited tumor cell growth, while the adenylyl cyclase activator forskolin and other PDE inhibitors had no effect. HMEC were found to express several cGMP hydrolyzing PDE isozymes (PDE1, 5, and 9), while the breast tumor cells expressed predominantly PDE5, which was confirmed to be sensitive to inhibition by SS using a recombinant enzyme. This work demonstrates that inhibition of PDE5A, elevation of cGMP, and activation of PKG are responsible for the pro-apoptotic effects of SS in human breast tumor cells and that differential expression of PDE isozymes between normal and tumor cells may explain the tumor selectivity of NSAIDs. These data also suggest that it may be feasible to develop NSAID derivatives with increased selectivity for inhibiting PDE5 and decreased COX-inhibitory activity, which would potentially improve safety and efficacy for breast cancer chemoprevention.

Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1041.
Immunohistochemical Phenotype after 20-Year Follow-Up of the Royal Marsden Tamoxifen Breast Cancer Prevention Trial (RMTBCPT).
Authors: Detre S. , Ashley S. , Tidy A. , Smith I. , Powles T. , Dowsett M.
Published: December 2010

Background: 20-yrs after starting the randomized, double-blind RMTBCPT (13-year median follow-up) 186 women developed invasive breast cancer, 82 on tamoxifen and 104 on placebo1. There was a significant reduction in the incidence of invasive ER+ but not ER- breast cancer that was significant after but not during the 8yr treatment period. The phenotype of ER+ breast cancer is highly variable. We have therefore assessed PgR, HER2, EGFR and Ki67 expression in as many as possible of these tumours.Methods: Tumour blocks were available on 154 participants, 65 on tamoxifen and 89 on placebo a similar distribution to the whole population. Staining was conducted using the following antibodies: ER, clone 6F11(Vector); PgR, clone 16 (Vector); HER2, HercepTest + K5207 (Dako), FISH PathVysion (Abbott) for IHC 2+ cases; EGFR, clone 31G7 (Invitrogen); Ki67 clone Mib1(Dako). ER and PgR were quantified as H-scores, HER2 and EGFR as + or –, and Ki67 as % cells staining.Results: There were 47 and 18 ER+ and ER- tumours in the tamoxifen arm vs 76 and 13 in the placebo arm, showing a 37% (95% CI 10- 57%, p=0.01) reduction of ER+ tumours which was essentially the same as that in the whole population1.There were 38 and 27 PgR+ and PgR- tumours in the tamoxifen arm vs 58 and 31 in the placebo arm, showing a 33% (95% CI 0-56%, p=0.05) reduction of PgR+ tumours. The distribution of ER/PgR tumours according to arm and time on trial at tumour diagnosis is shown in the table (there were no ER-PgR+ cases).The decrement in ER+ tumours was predominantly in ER+PgR+ cases after 8yrs but extended to ER+PgR- cases. It is important to note that the post 8yr tumour phenotype cannot be affected by continued exposure to tamoxifen. ER levels were significantly lower in the tamoxifen-treated group even among tumours presenting as ER+ (median H-score 123 vs 161, p=0.02). There were 9 and 6 HER2+ and 11 and 12 EGFR+ cases in the tamoxifen and placebo arms, respectively (p=NS for both). The mean (95%CI) levels of Ki67 were 8.4% (6.3-11.1) and 8.5% (6.8-10.6) in the 2 arms, respectively.Discussion: The decrement in ER+ tumours in the tamoxifen-treated women was restricted to the post-treatment period and was similar to that seen in the overall population1. Among the ER+ group there was a similar proportional reduction of PgR+ and PgR- tumours by tamoxifen.There was no evidence of enhanced HER2 or EGFR expression or increased proliferation in tumours developing in the tamoxifen arm but ER expression was reduced even among ER+ tumours.1Powles et al, JNCI, 2007;99:283-90. Time on trialPlaceboTamoxifenER+PgR+<8 years2622ER+PgR+>8 years3216ER+PgR-<8 years106ER+PgR->8 years83ER-PgR-<8 years711ER-PgR->8 years67All<8 years4339All>8 years4626 Supported by the Da Costa International Fund for Breast Cancer Prevention

Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1046.
Prognostic Effect of Sesrum 25 Hydroxyvitamin D Levels in Breast Cancer Patients.
Authors: Kim H. , Lim W. , Son B. , Kim M. , Jeong K. , Kim S. , Ahn J. , Gong G. , Kim H. , Yeom C. , Ahn S.
Published: December 2010

BackgroundThere is increasing evidence that vitamin D has been linked to breast cancer risk, but prognosis effect are unknown. We investigated the possible association between vitamin D and breast cancer prognosis by comparing serum vitamin D levelMethodsFrom June to December 2006, serum 25 OHD were measured in 310 Korean women with breast cancer at the Asan Medical Center. Clinical, Pathologic, and dietary data were accessed to examine prognostic effects of serum 25 OHDResultsMean age was 48.7 years, mean serum 25OHD was 31.4±16.1ng/ml. 25OHD levels were deficient(<20ng/ml) in 24.2%, insufficient (20-29ng/ml) in 30.6%, and sufficient(30-150ng/ml) in 24.0%. Mean follow up was 30 months: 31 had recurrences. Women with deficient 25 OHD levels had an increased risk of recurrence(HR=2.93;95% CI=1.27 to 6.77) compared with those with sufficient levels. 25OHD levels were inversely associated with prognosis of hormone receptor positive tumors, but not with hormone receptor negative tumors(HR=5.73 95CI=1.82 to 18.06 for hormone receptor positive tumor, HR=1.142, 95%CI =0.33 to 3.92 for hormone receptor negative tumor). The association remained after individual adjustment for age, tumor size, nodal status, estrogen receptor status (HR=4.13 95%CI=1.77 to 9.61) .ConclusionVitamin D deficiency may be associated with poor outcomes in hormone receptor positive breast cancer patients.

Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1052.
Deleterious Effect of Chemotherapy on Measures of Insulin Resistance in Patients with Newly-Diagnosed Invasive Breast Cancer.
Authors: Makari-Judson G. , Katz D. , Barham R. , Mertens W.
Published: December 2010

Background: Women treated with early stage breast cancer often gain weight in the two years following diagnosis, with adjuvant chemotherapy, younger age, lower body mass index (BMI) and pretreatment menopausal status being associated factors (Breast J 2007; 13:258). The effect of insulin resistance on treatment-related weight gain, and of treatment on measures of insulin resistance, are unclear.Purpose: To prospectively study weight gain in women receiving adjuvant therapy for early stage breast cancer and assess changes in body mass index, body composition, and explore the relationship between markers of insulin resistance, cancer therapy, exercise and weight gain.Methods: Prospective, observational study of non-diabetic women with early-stage breast cancer receiving adjuvant chemotherapy and/or hormonal therapy. Fasting insulin, glucose, and triglycerides, weight, BMI, waist and hip circumference were obtained at baseline before adjuvant therapy, and at 6, and 12 months. Patients completed nutrition and exercise logs using the Nutritionist-Pro program. Insulin resistance was calculated using the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). Waist/hip ratio (WHR) was used as a surrogate for percent body fat.Results: Complete data available for 95 patients are reported regarding weight change at 6 months (mean 0.4 kg, 95%CI -0.3, 1.0; p=.23 compared to baseline) and 12 months (0.9 kg, 95%CI 0.4, 1.8, p=.04 compared with baseline). Mean baseline HOMA-IR was 2.3 (95%CI 1.9, 2.7); mean baseline WHR was 0.82 (95%CI 0.81, 0.84). Six-month HOMA-IR tended to increase (by mean 0.34, p=.06) as did glucose/insulin ratio (p=.05). Waist measurement (p=.96) and WHR (p=.52) were unchanged. Chemotherapy-treated patients exhibited adverse changes compared with others (mean change for chemotherapy-treated and no chemotherapy for HOMA-IR: 0.53 vs. -0.64, p=.005; glucose/insulin: -2.1 vs. 2.7, p=.003; waist: 0.37 vs. -1.94 cm, p=.08; WHR: 0.001 vs. -0.024, p=.06). Age, BMI, hormonal therapy, or types of breast surgery were not associated with significant changes. Exercising patients demonstrated lower HOMA-IR and WHR, and greater glucose/insulin ratios at baseline, but exercise (aerobic, strength, or any exercise) was not associated with significant change at 6 and 12 months for any of these variables. While differences disappeared at 12 months despite further weight gain repeated measures analysis of variance confirmed the effect of chemotherapy over time for HOMA-IR (p=.048), glucose/insulin (p=.038) and WHR (p=.050).Conclusions: These preliminary data suggest that patients completing chemotherapy within 6 months of baseline appear to experience at least short-term changes in metabolism suggestive of insulin resistance. These adverse changes may help explain weight gain associated with adjuvant chemotherapy, and merit further prospective study.

Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1054.