bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantifying Optical Microangiography Images Obtained from a Spectral Domain Optical Coherence Tomography System
Authors: Reif Roberto , Qin Jia , An Lin , Zhi Zhongwei , Dziennis Suzan , Wang Ruikang
Published: June 2012

The blood vessel morphology is known to correlate with several diseases, such as cancer, and is important for describing several tissue physiological processes, like angiogenesis. Therefore, a quantitative method for characterizing the angiography obtained from medical images would have several clinical applications. Optical microangiography (OMAG) is a method for obtaining three-dimensional images of blood vessels within a volume of tissue. In this study we propose to quantify OMAG images obtained with a spectral domain optical coherence tomography system. A technique for determining three measureable parameters (the fractal dimension, the vessel length fraction, and the vessel area density) is proposed and validated. Finally, the repeatability for acquiring OMAG images is determined, and a new method for analyzing small areas from these images is proposed.
Multimodality Imaging in the Assessment of Thoraco-Omphalopagus Conjoined Twin: Lessons to Learn
Authors: Chelliah Kanaga Kumari , Faizah M. Z. , Dayang A. A. , Bilkis A. A. , Shareena I. , Mazli M.
Published: June 2012

Conjoined twins are rare and present a unique challenge to pediatric surgeons and radiologists. An imaging strategy to accurately define anatomic fusion, vascular anomalies, and other associated abnormalities is important for surgical planning and prognostic information. A conjoined female twin with a combined weight of 2.8 kg was born by emergency caeserean. Hence, a computed tomography scan of the thorax and entire abdomen at 1.25 mm slice thickness was performed to delineate the internal structures of the twins. CT-angiography defined specific vascular supply which determined the distribution of shared structures between the twins. An echocardiogram showed four heart chambers with atrioventricular septal defect. To further evaluate the heart chambers, the twin was planned for gated cardiac magnetic resonance imaging. Unfortunately, they succumbed 6 hours apart due to complication of septicemia. Magnetic resonance imaging and CT scan provide excellent anatomic detail, demonstrating organ position, shared viscera, and limited vascular anatomy, whilst angiography defined specific vascular supply, useful in determining the distribution of shared structures between the twins in planning for surgery.
Local and Systemic Cardiovascular Effects from Monochromatic Infrared Therapy in Patients with Knee Osteoarthritis: A Double-Blind, Randomized, Placebo-Controlled Study
Authors: Hsieh Ru-Lan , Liao Wei-Cheng , Lee Wen-Chung
Published: June 2012

Infrared (IR) therapy is used for pain relief in patients with knee osteoarthritis (OA). However, IR’s effects on the cardiovascular system remain uncertain. Therefore, we investigated the local and systemic cardiovascular effects of monochromatic IR therapy on patients with knee OA in a double-blind, randomized, placebo-controlled study. Seventy-one subjects with knee OA received one session of 40 min of active or placebo monochromatic IR treatment (with power output of 6.24 W, wavelength of 890 nm, power density of 34.7 mW/cm2for 40 min, total energy of 41.6 J/cm2per knee per session) over the knee joints. Heart rate, blood pressure, and knee arterial blood flow velocity were periodically assessed at the baseline, during, and after treatment. Data were analyzed by repeated-measure analysis of covariance. Compared to baseline, there were no statistically significant group x time interaction effects between the 2 groups for heart rate (P=0.160), blood pressure (systolic blood pressure:P=0.861; diastolic blood pressure:P=0.757), or mean arterial blood flow velocity (P=0.769) in follow-up assessments. The present study revealed that although there was no increase of knee arterial blood flow velocity, monochromatic IR therapy produced no detrimental systemic cardiovascular effects.
Dynamic Difficulty Balancing for Cautious Players and Risk Takers
Authors: Hawkins Guy , Nesbitt Keith , Brown Scott
Published: June 2012

Dynamic balancing of game difficulty can help cater for different levels of ability in players. However, performance in some game tasks depends on not only the player's ability but also their desire to take risk. Taking or avoiding risk can offer players its own reward in a game situation. Furthermore, a game designer may want to adjust the mechanics differently for a risky, high ability player, as opposed to a risky, low ability player. In this work, we describe a novel modelling technique known as particle filtering which can be used to model various levels of player ability while also considering the player's risk profile. We demonstrate this technique by developing a game challenge where players are required to make a decision between a number of possible alternatives where only a single alternative is correct. Risky players respond faster but with more likelihood of failure. Cautious players wait longer for more evidence, increasing their likelihood of success, but at the expense of game time. By gathering empirical data for the player's response time and accuracy, we develop particle filter models. These models can then be used in real-time to categorise players into different ability and risk-taking levels.
Desferrioxamine Attenuates Pancreatic Injury after Major Hepatectomy under Vascular Control of the Liver: Experimental Study in Pigs
Authors: Varsos Panagiotis , Nastos Constantinos , Papoutsidakis Nikolaos , Kalimeris Konstantinos , Defterevos George , Nomikos Tzortzis , Pafiti Agathi , Fragulidis George , Economou Emmanuel , Kostopanagiotou Georgia , Smyrniotis Vassilios , Arkadopoulos Nikolaos
Published: June 2012

Introduction. Pancreatic injury can manifest after major hepatectomy under vascular control. The main mechanism involved seems to be remote oxidative injury due to “spillage” of reactive oxygen species and cytokines from the liver. The aim of this study is to evaluate the role of desferrioxamine in the prevention of pancreatic injury following major hepatectomy.Methods. Twelve Landrace pigs were subjected to a combination of major hepatectomy (70–75%), using the Pringle maneuver for 150 minutes, after constructing a porta-caval side-to-side anastomosis. The duration of reperfusion was 24 hours. Animals were randomly divided into a control group (n=6) and a desferrioxamine group (DFX,n=6). DFX animals were treated with continuous IV infusion of desferrioxamine 100 mg/kg. Pancreatic tissue injury, c-peptide and amylase concentrations, and pancreatic tissue oxidative markers were evaluated.Results. Desferrioxamine-treated animals showed decreased c-peptide levels, decreased acinar cell necrosis, and decreased tissue malondialdehyde levels 24 hours after reperfusion compared with the control group. There was no difference in portal pressure or serum amylase levels between the groups.Conclusions. Desferrioxamine seems to attenuate pancreatic injury after major hepatectomy under vascular control possibly by preventing and reversing production and circulation of oxidative products.
Beneficial Effects ofOcimum gratissimumAqueous Extract on Rats with CCl4-Induced Acute Liver Injury
Authors: Chiu Chun-Ching , Huang Chih-Yang , Chen Tzy-Yen , Kao Shao-Hsuan , Liu Jer-Yuh , Wang Yi-Wen , Tzang Bor-Show , Hsu Tsai-Ching
Published: June 2012

Ocimum gratissimum(OG) is known as a food spice and traditional herb, which has been recommended for the treatment of various diseases. To investigate the hepatoprotective effect of OG aqueous extract (OGAE), male Wistar rats challenged by carbon tetrachloride (CCl4) were used as the animal model of chronic hepatic injury. Significantly increased serum catalase and DPPH levels were detected in CCl4-administrated rats that were treated with OGAE or silymarin as compared to those rats that were treated with saline or CCl4. In contrast, significantly decreased stress proteins including HSP70 and iNOS were observed in livers of CCl4-administrated rats that were treated with OGAE or sylimarin as compared to those rats that were treated with saline or CCl4. Moreover, significant decreases of MMP-9/MMP-2 ratio, uPA, phosphorylated ERK (p-ERK) and NF-κB (p-P65) were detected in livers of CCl4-administrated rats that were treated with OGAE or sylimarin as compared to those rats that were treated with saline or CCl4. These findings imply that OGAE can efficiently inhibit CCl4-induced liver injuries in rats and may therefore be a potential food or herb for preventing liver injuries.
In VitroAntiparasitic and Apoptotic Effects of Antimony Sulfide Nanoparticles onLeishmania infantum
Authors: Soflaei Saied , Dalimi Abdolhossein , Ghaffarifar Fatemeh , Shakibaie Mojtaba , Shahverdi Ahmad Reza , Shafiepour Mohsen
Published: June 2012

Visceral leishmaniasis is one of the most important sever diseases in tropical and subtropical countries. In the present study the effects of antimony sulfide nanoparticles onLeishmania infantum in vitrowere evaluated. Antimony sulfide NPs (Sb2S5) were synthesized by biological method fromSerratia marcescensbacteria. Then the cytotoxicity effects of different concentrations (5, 10, 25, 50, and 100 μg/mL) of this nanoparticle were assessed on promastigote and amastigote stages ofL. infantum. MTT method was used for verification results of promastigote assay. Finally, the percentages of apoptotic, necrotic, and viable cells were determined by flow cytometry. The results indicated the positive effectiveness of antimony sulfide NPs on proliferation of promastigote form. The IC50(50% inhibitory concentration) of antimony sulfide NPs on promastigotes was calculated 50 μg/mL. The cytotoxicity effect was dose-dependent means by increasing the concentration of antimony sulfide NPs, the cytotoxicity curve was raised and the viability curve of the parasite dropped simultaneously. Moreover, the IC50of antimony sulfide NPs on amastigote stage was calculated 25 μg/mL. On the other hand, however, antimony sulfide NPs have a low cytotoxicity effect on uninfected macrophages but it can induce apoptosis in promastigote stage at 3 of 4 concentrations.
Endoscopic Endonasal Transturbinate Approach to the Pterygopalatine Fossa in the Management of Juvenile Nasopharyngeal Angiofibromas
Authors: Kodama Satoru , Mabuchi Hideaki , Suzuki Masashi
Published: June 2012

Pterygopalatine fossa (PPF) is a difficult-to-access anatomic area located behind the posterior wall of the maxillary sinus. Juvenile nasopharyngeal angiofibroma (JNA) often affects this area, and the management of feeding artery to the tumor is important in the surgery. Endoscopic endonasal approach to the PPF without endangering all other nasal structures is useful in the management of JNA. We describe a new approach to the PPF, endoscopic transturbinate approach, which is effective in the management of JNA. Submucous inferior turbinoplasty was performed, and sphenopalatine artery, the feeder to the tumor, was identified at the sphenopalatine foramen. The posterior wall of maxillary sinus was removed. Internal maxillary artery was identified in the PPF and was ligated with a hemoclip. The tumor in the PPF was pushed into the nasal cavity. These procedures were all performed via submucous turbinate tunnel. Then, the tumor was successfully removed in en bloc from the nasal cavity by transnasal approach without ethmoidectomy. This approach improves accessibility and visualization in the PPF and potential to reduce intraoperative bleeding due to ligation of the feeder safely without touching the tumor. Endoscopic transturbinate approach is effective in the management of early stage of JNA.
One‐Step Method for Preparation of Magnetic Nanoparticles Coated with Chitosan
Authors: Gregorio-Jauregui Karla M. , Pineda Ma. Guadalupe , Rivera-Salinas Jorge E. , Hurtado Gil , Saade Hened , Martinez José L. , Ilyina Anna , López Raúl G.
Published: June 2012

Preparation of magnetic nanoparticles coated with chitosan in one step by the coprecipitation method in the presence of different chitosan concentrations is reported here. Obtaining of magnetic superparamagnetic nanoparticles was confirmed by X‐ray diffraction and magnetic measurements. Scanning transmission electron microscopy allowed to identify spheroidal nanoparticles with around 10‐11 nm in average diameter. Characterization of the products by Fourier transform infrared spectroscopy demonstrated that composite chitosan‐magnetic nanoparticles were obtained. Chitosan content in obtained nanocomposites was estimated by thermogravimetric analysis. The nanocomposites were tested in Pb2+ removal from a PbCl2 aqueous solution, showing a removal efficacy up to 53.6%. This work provides a simple method for chitosan‐coated nanoparticles obtaining, which could be useful for heavy metal ions removal from water.
Warped Product Submanifolds of LP‐Sasakian Manifolds
Authors: Hui S. K. , Uddin S. , Özel C. , Mustafa A. A.
Published: June 2012

We study of warped product submanifolds, especially warped product hemi‐slant submanifolds of LP‐Sasakian manifolds. We obtain the results on the nonexistance or existence of warped product hemi‐slant submanifolds and give some examples of LP‐Sasakian manifolds. The existence of warped
product hemi‐slant submanifolds of an LP‐Sasakian manifold is also ensured by an interesting example.
Epidermal Growth Factor Receptor Expression in Esophageal Adenocarcinoma: Relationship with Tumor Stage and Survival after Esophagectomy
Authors: Navarini Daniel , Gurski Richard R. , Madalosso Carlos Augusto , Aita Lucas , Meurer Luise , Fornari Fernando
Published: June 2012

Background and Aims. Esophageal adenocarcinoma (EA) is an aggressive tumor with increasing incidence in occidental countries. Several prognostic biomarkers have been proposed, including epidermal growth factor receptor (EGFR). The aim of this study was to assess whether EGFR expression predicts EA staging and patient survival.Methods. In this historical cohort, consecutive patients with EA managed between 2000 and 2010 were considered eligible for the study. Surgical specimens of patients treated with transhiatal esophagectomy were evaluated to establish EGFR expression and tumor differentiation. Staging was classified according with tumor-node-metastasis (TNM) system. Survival was determined according to either medical register or patient’s family contact.Results. Thirty-seven patients who underwent esophagectomy without presurgical chemotherapy or radiotherapy were studied. EGFR expression was found in 16 patients (43%). EGFR expression was more frequent as higher was the TNM (I andII=0% versusIII=47% versusIV=100%;P<0.001). Average survival in months was significantly shorter in the group of patients with EGFR expression (10.5 versus 21.7;P=0.001).Conclusions. In patients with esophageal adenocarcinoma treated with transhiatal esophagectomy, EGFR expression was related to higher TNM staging and shorter survival. EGFR expression might be assumed as a prognostic marker for esophageal adenocarcinoma.
Synchronization of the Extended Bonhoffer‐Van der Pol Oscillators
Authors: Zribi Mohamed , Alshamali Saleh
Published: June 2012

This paper deals with the synchronization of two extended Bonhoffer‐Van der Pol (B‐VDP) oscillators. A Lyapunov‐based controller and a sliding mode controller are proposed for the synchronization
of the oscillators. Both design schemes use a single input controller acting on one state only. Asymptotic stability results for the closed‐loop system are derived using Lyapunov theory. It is shown that the proposed controllers effectively synchronize the driver and the response systems for the case when nominal values of the system parameters are used, and for the case when parameter perturbations are introduced. Simulation results are presented to show the effectiveness of the proposed controllers.
Chemical Composition of Iran′s Pistacia atlantica Cold‐Pressed Oil
Authors: Saber-Tehrani M. , Givianrad M. H. , Aberoomand-Azar P. , Waqif-Husain S. , Jafari Mohammadi S. A.
Published: June 2012

The lipid fraction of Pistacia atlantica seeds was extracted for the first time by means of cold‐press technique and analyzed for its chemical composition. The fatty acids, sterols, triacylglycerols (TAG), tocopherols, polyphenols, and pigments were identified and their concentrations were determined by means of reversed‐phase high‐performance liquid chromatography (RP‐HPLC) and gas chromatography (GC). Because of its high content of unsaturated fatty acids, it might prove to be of value in diets and it may be used as edible cooking or salad oils or for margarine manufacture. Pistacia atlantica seed oil has the unique sterols and tocopherols content providing source of natural antioxidants. The main triacylglycerols were SLL + PLO, SOL + POO, OOLn + PLL, OOO, and SOO. This paper examined the phenolic fraction of Pistacia atlantica seed oil. Moreover, caffeic acid followed by cinnamic acid, pinoresinol, vanillin,
p‐Coumaric acid, ferulic acid, and o‐Coumaric acid was also determined.
This paper presents the first investigation of chlorophyll′s and carotene′s composition in Pistacia atlantica seed oil. Furthermore, pheophytin a was the major component, followed by luteoxanthin, neoxanthin, violaxanthin, lutein, lutein isomers, chlorophyll a, chlorophyll a′, and pheophytin a′ were also determined.
Rapid Microwave Digestion Procedures for the Elemental Analysis of Alloy and Slag Samples of Smelted Ocean Bed Polymetallic Nodules
Authors: Smita Kumari , Singh Saurabh Kumar , Kumar Brajesh
Published: June 2012

The use of microwave digester for digestion of alloy and slag samples of smelted ocean bed polymetallic nodules has permitted the complete digestion of samples, thereby replacing the tedious classical methods of digestion of samples. The digestion procedure includes two acid‐closed digestions of samples in a microwave oven. Owing to the hazardous nature of perchloric acid, it was not used in developed digestion procedure. Digested sample solutions were analyzed for concentrations of various radicals and the effectiveness of the developed digestion methodology was tested using certified reference materials. It was found that the developed method is giving results comparable with that obtained from conventionally digested samples. In this digestion procedure, time required for digestion of samples was reduced to about 1 hour only from 8‐9 hours of conventional digestion.
A New Pentacyclic Triterpene from Humata tyermanni Moore with the Inhibitory Activities against LPS‐Induced NO Production in RAW264.7 Macrophages
Authors: Zhang Lei , Wang Feng , Jiang Zhen-You , Zhu Yao-Kui , Cen Ying-Zhou
Published: June 2012

One new pentacyclic triterpene, hopane‐22 (29)‐en‐24ol (2), with five known hopane‐type pentacyclic triterpene compounds: hop‐22(29)‐ene (1), adiantone (3), 22‐hydroxyhopane (4), 6α, 22‐dihydroxyhopane (5), and 17(21)‐hopene (6) were isolated from Humata tyermanni Moore. The structure of compound 2 was elucidated on the basis of its 1D and 2D NMR spectral analysis. All these compounds were evaluated for their inhibitory activities of LPS‐induced nitric oxide (NO) production in RAW264.7 macrophages.
BS2-2: Nuclear Receptor Coactivators: Physiology and Disease.
Authors: O'Malley BW
Published: June 2012

Nuclear receptors control gene expression by recruiting transcriptional coactivators (or corepressors). The coactivators are ‘master regulators’ that activate genes to control physiologies such as reproduction, growth and metabolism. Consequently, they are major players in the development of many inherited and acquired endocrine-related pathologies such as fertility/endometriosis, cancers, and disorders of carbohydrate, lipid and protein metabolism. The coactivator proteins provide important insights to polygenic diseases and represent a new class of drug targets for therapeutic interventions.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr BS2-2.
ES1-3: Treatment of Metastatic Breast Cancer – Breast Cancer as a Chronic Disease: Triple Negative Breast Cancer.
Authors: Stearns V
Published: June 2012

Carcinomas of the breast that do not express the estrogen or progesterone receptors (ER/PR) and are not associated with over-expression or amplification of HER2/neu have been designated triple negative breast cancer. These tumors represent approximately 15–20% of all breast cancers, but are more prevalent in younger women, in African Americans, and in BRCA1 mutation carriers. Molecular profiling data suggest that many of triple negative tumors, but not all, are basal-like. The basal-like tumors are more likely to be resistant to standard therapies resulting in disease recurrence and poor prognosis. It is likely that triple negative breast cancer will be further sub classified to several additional distinct subtypes. Regardless of additional sub classification of the entity, the only treatment currently available for women with triple negative breast cancer is chemotherapy-based. In this symposium, I will review current molecular classification, prognosis and predictive markers, treatment options, emerging approaches, and clinical trials.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr ES1-3.
ES6-1: Oncofertility: Translation in Multiple Dimensions.
Authors: Woodruff TK
Published: June 2012

Cancer is now a disease with a variety of treatment options, which are leading to longer and more productive lives by survivors. Globally, there are 10 million people diagnosed with cancer. 10% of these newly diagnosed men and women are under the age of 45 years old. Infertility can be a consequence of many of the more aggressive chemo- and radiation therapies that prolong and save lives. The ability to easily preserve sperm prior to cancer treatment provides hope at the time of diagnosis and families later in life for male survivors. A notable example is Tour de France winner Lance Armstrong who has three children conceived using sperm frozen days before he underwent the massive chemo- and radiation therapy that saved his life. Unlike sperm, the female germ cell, the oocyte or egg must be retrieved surgically. Moreover, the vast majority of collected oocytes will be immature and cannot be used immediately by a woman who is ready to start a family. The overall hypothesis of the program is that effective fertility-extending options can be provided to young women undergoing life-preserving cancer treatment. The purpose of our work is to bring physicians, medical ethicists, social scientists and basic scientists together to develop new strategies for fertility preservation for female cancer survivors under the new discipline of oncofertility. At the basic science level, complex issues of ovarian function and preservation must be addressed including the problem of follicle growth and development in vitro. Our investigative group has developed a 3-dimensional system that supports follicle development, largely, we believe, because the links between the oocyte and its surrounding cells are maintained. The goal of our program and the broader Oncofertility Consortium is to explore and expand the reproductive options available to young people facing a fertility-threatening but life-preserving cancer treatment.

This work is supported by NIH/NICHD Structure-Function Relationships in Reproductive Science, U54 HD041857; and, the Oncofertility Consortium, UL1DE019587 and RL1HD05829 http://oncofertility.northwestern.edu/

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr ES6-1.
OT1-02-13: Cardiac Biomarkers on Trastuzumab (Cabot Trial): Determining the Cardiac Biomarker Profile in Breast Cancer Patients Receiving Adjuvant Trastuzumab Therapy.
Authors: Kumar VNC , Kavsak P , Rask S , Mukherjee SD , Ellis P , Dhesy-Thind B
Published: June 2012

Background

Trastuzumab is a humanized anti-HER2 monoclonal antibody that has demonstrated a 50% reduction in the risk of HER2+ breast cancer recurrence. This benefit is at the risk of possible cardiac dysfunction. Detecting trastuzumab-related cardiotoxicity based on physical examination and assessment of left ventricular ejection fraction (LVEF) by serial echocardiography or multi gated acquisition (MUGA) scan, has low diagnostic sensitivity and low predictive power in detecting subclinical myocardial injury. There is interest in developing simple, non-invasive, and cost-effective tools for early identification of trastuzumab-related cardiotoxicity. Use of easily detectible cardiac biomarkers in blood, such as cardiac troponins (cTnT and cTnI) and natriuretic peptides (NPs), are being evaluated. Kavsak et al. have studied a high-sensitivity cTn (hs-cTn) assay that is 10-fold more sensitive, and may be able to identify evolving injury earlier when compared to the conventional cTn assays. B-type natriuretic peptide (BNP) has been established as an indicator for heart failure. Pro-BNP is secreted from the cardiac ventricles in response to increased pressure and volume and is divided into NT-pro-BNP and BNP. The longer half-life of NT-proBNP may make it a more accurate predictor of ventricular stress.

Trial design: This is a pilot single institution, prospective cohort study of 25 patients. Breast cancer patients will be seen at the Juravinski Cancer Centre, Hamilton, Canada. Biomarkers will be collected at baseline, then days 1 and 2 of every 21 day cycle for the first 3 months, then every 42 days for the next 3 months. LVEF will be measured at baseline and then every 3 months while on trastuzumab.

Eligibility criteria: Patients with stage I-III, HER2 positive (3+ by immunohistochemistry or FISH+) breast cancer receiving adjuvant trastuzumab therapy. Patients who have received prior trastuzumab therapy or are unable to provide informed consent will be excluded.

Specific aims: To determine the biological profile of cardiac biomarkers — cTnT, hs-cTn, and NT-proBNP — in patients on adjuvant trastuzumab; and, to determine if elevations in these biomarkers correlate with LVEF.

Statistical methods: A convenient sample size of 25 patients will be entered into this pilot study. The minimum of 20 patients is a requirement by the Clinical Laboratory Standards Institute (CLSI) to formally accept existing reference ranges for the cardiac biomarkers to be used in the HER2 breast cancer population (National Committee for Clinical Laboratory Standards (NCCLS)).

Present accrual and target accrual: 8 patients have enrolled to date.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT1-02-13.
OT1-03-02: SAFIR01: A Molecular Screening Trial for Metastatic Breast Cancer Patients.
Authors: Andre F , Peletekian C , Jimenez M , Ferrero JM , Delaloge S , Roman Roman S , Dessen P , Bonnefoi H
Published: June 2012

Background: High number of new drugs are targeting molecular alterations that occur in a few number of patients. Molecular screening that consists in the assessment of single molecular alteration during the screening phase of the therapeutic trial is not suitable. Indeed, this modality of screening is associated with a high rate of screen failure due to the low incidence of the molecular alteration. In order to optimize molecular screening, we have launched a clinical trial that aims at performing array CGH and hot spot mutations in patients with metastatic breast cancer.

Patients and Methods. The trial plans to include 400 patients with metastatic breast cancer and included the first patient in may 2011. This trial is being sponsored by French federation of Cancer centers (UNICANCER) and involves 20 centers. Biopsy is being performed on metastatic site. Both frozen and FFPE samples are obtained. DNA extraction is being performed in the investigation center after control for the % of cancer cells. Array CGH and PIK3CA/AKT mutations (SANGE method) are being performed in four genomic platforms. A pilot study that included 106 patients has shown the feasibility of such technologies in the context of daily practice. Data from array CGH are being sent to a bioinformatician who forward the results on both pre-selected targets, DNA instability and some targets of interest selected based on log2(ratio) and function. Recommendations for trials are then being sent to each investigator. There is no limitation for previous lines and it is recommended to perform biopsy in patients who do not present progressive disease. This trial is being funded by French NCI (750 000 euros)

Conclusion: SAFIR01 is a trial that aims at using high throughput technologies in order to drive patients with molecular alterations to specific therapeutic trials. Further amendments are being planned including implementation of high throughput sequencing and performance of functional testing. Further trial will compare this high throughput approach to standard methods for target identification.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT1-03-02.
OT2-01-04: Cardiac Safety of Anthracycline-Containing Adjuvant Chemotherapy of Early Breast Cancer: OSCAR/ABC Ongoing, Observational, Multicentric Study.
Authors: Ricevuto E , Cocciolone V , Zilli M , Scognamiglio MT , Pistilli B , Di Menna G , Mancini M , Cannita K , Adinolfi MI , Ferrandina MG , Pancotti A , Recchia F , Latini L , Ficorella C , Iacobelli S
Published: June 2012

BACKGROUND: Among the different chemotherapeutic options available for adjuvant treatment of early breast cancer (EBC), anthracycline-containing regimens represent prevalent choices. OSCAR/ABC is an observational, prospectic, multicentric study aimed at evaluating, in the clinical practice, the relevance of cardiac dysfunction and congestive heart failure (CHF) associated to “free choice”, anthracycline-containing adjuvant regimens and to identify patients at increased cardiac risk. PATIENTS AND METHODS: patients candidate to receive adjuvant anthracycline-containing chemotherapy, will be enrolled in the study. Data on demographic and clinical characteristics of patients (age, cardio-vascular comorbidity) tumor features (TNM, histotype, ER and PgR status, Ki67, and HER2 status), type of adjuvant regimen and tolerability of treatment will be collected and centrally registered at the Consorzio Interuniversitario Nazionale per ***1a Bio-Oncologia (CINBO) using e-CRFs. Data on type, sites and doses of radiotherapy performed will be collected, to evaluate the possible impact on cardiac function. Primary aim of the study is to evaluate the prevalence of cardiac dysfunction and CHF among the whole population enrolled, particularly according to risk criteria and type of administered chemotherapy. Cardiac dysfunction is defined as limiting cardio-vascular toxicity (≥ Grade 3 dyspnea, arrhytmia, hypertension) and/or asymptomatic LVEF reduction ≥20% (if >50% at the baseline) or ≥10% (if ≤50% at baseline); CHF is defined as clinical diagnosis and/or symptomatic LVEF reduction ≥20% (if >50% at the baseline) or ≥10% (if ≤50% at baseline). Assessment of cardiac risk involves the evaluation of age (< vs ≥ 65 years), cardio-vascular comorbidities (requiring treatment or not) and Left-Ventricular Ejection Fraction LVEF (> vs ≤ 55%) at diagnosis. Clinical and instrumental cardiac evaluation (ECG, Ecocardiography) will be performed at study entry, on-treatment and up to 5 years thereafter. Secondary objective of the study is to evaluate the clinical properness of different adjuvant anthracyclines-containing chemotherapy options, with regard to prevalence of therapeutic regimens, safety, efficacy (DFS and OS) and costs analysis. Cardiac safety and general toxicity on-treatment will be evaluated according to NCI criteria. The expected enrollment is 1,200 patients in 36 months. From September 2010 to May 2011, 7 of the 13 Centers involved in the study are active, with 65 enrolled patients.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT2-01-04.
OT2-04-01: A Randomized Phase II Trial of Vitamin D vs Placebo in Premenopausal Women: CALGB 70806.
Authors: Wood ME , Kingsley F , Ambaye AB , Yee L , Jung S-H , Marshall JR , Paskett E
Published: June 2012

Background

Chemoprevention studies are long and expensive. Gaining information about the feasibility of an agent using biomarker endpoints can save money and ensure that only the most promising agents move forward. There is strong evidence to suggest breast cancer prevention properties for vitamin D. The safety and tolerability of this agent makes it a perfect candidate for a chemopreventive agent. This clinical trial will evaluate the effect of vitamin d on several breast cancer; providing important information regarding the feasibility of a larger chemoprevention study using cancer development as the endpoint. Successful completion of this study will also validate this design of biomarker testing of potential chemoprevention agents within a cooperative group setting and add to data validating these specific biomarkers.

Methods: This is a randomized placebo controlled trial of one year of 2000 units of vitamin D (cholecalciferol) for premenopausal women (≥ 35 years) with increased breast density. The primary aim of this study is to evaluate the effect of vitamin D on breast density. Secondary aims include evaluation of vitamin D effects on IGF1 and markers of cellular proliferation (Ki-67 and atypia). In addition 3 methods of density analysis (Breast Imaging Reporting and Data System (BI-RADS), Visual Analogue Scale (VAS), and the Boyd method) will be compared. For the primary endpoint of change in mammographic density we will have an 87% power to detect a standardized effect size (difference in means divided by standard deviation) of 0.4 in change of mammographic density between two arms. The target effect size is 2.64%.This study was activated 10/15/2010 and has been opened at 75 sites with 15 patients enrolled. Target accrual is 250.

Funding: This study is sponsored by the NCI and CALGB.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT2-04-01.
OT2-04-02: Metformin for Breast Cancer Prevention: A Pilot Study.
Authors: Ledgerwood MM , Ojeda-Fournier H , Patterson R , Hasteh F , Andre MP , Cadmus L , Blair S
Published: June 2012

Background

There is a body of accumulating evidence connecting metformin, a biguanide derivative which reduces hepatic gluconeogensis and improves skeletal muscle insulin sensitivity, to reduced breast cancer risk. This, in addition to a well established drug safety record among diabetics and non-diabetics, has provoked an interest in further study of metformin's effects on breast cancer risk indicators. In our study, we examine the effects of metformin on breast density and proliferative cell marker Ki67, both indicators of breast cancer risk. This is a small observational pilot study to determine the feasibility of subject recruitment, data collection through fine-needle aspiration, and breast density measurement.

Trial Design: Recruitment of 10 breast surgery patients with high risk histology to: 1. Undergo peri-areolar fine needle aspiration (RPFNA) used to collect breast cells for analysis of proliferative marker Ki67. 2. Breast density assessment by a) mammography (the standard method) and b) whole-breast ultrasound (an innovative method recently developed at UCSD).

Each subject will undergo a single view mammogram, whole-breast ultrasound, and intra-operative RPFNA. No drug or therapeutic intervention will take place in this pilot study.

Eligibility: Female undergoing excisional high risk breast surgery.

Specific Aims: Aim 1. To determine the feasibility of recruiting high risk breast surgery patients to an observational study involving RPFNA, mammography, and whole-breast ultrasound.

Aim 2. a) To compare mammography and whole-breast ultrasound for measurement of breast density. b) To examine potential for detecting biomarkers of cell proliferation through RPFNA.

Statistical Method: Breast density will be determined by the ratio of fibroglandular tissue to fat measured on mammogram and WBU. Cell proliferation will be assessed by the percentage of positivity for biomarker Ki67 in breast ductal cells.

Accrual and target accrual: Five of ten breast excisional high risk breast surgery subjects have been accrued at this time.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT2-04-02.
OT2-07-01: Pasireotide Long Acting Release (LAR) in Breast Cancer Patients To Prevent Lymphocele after Mastectomy and Axillary Node Dissection: A Randomized, Multicenter, Phase II Study.
Authors: Chereau E , Uzan C , Bezu C , Mazouni C , Ballester M , Gouy S , Rimareix F , Garbay J-R , Daraï E , Uzan S , Coutant C , Rouzier R
Published: June 2012

Background: Lymphocele is the principal post-operative morbidity following axillary node dissection. According to the literature, incidence can vary from 4 to 89%.

Encouraging results in terms of reducing postoperative lymphoceles as well as drainage duration and volume using octreotide have been recorded recently. A new molecule, namely pasireotide, developed by Novartis Pharma AG, Basle Switzerland, is a somatostatin analog possessing high binding affinity to 4 of the 5 somatostatin receptors. Trial design: We are performing a prospective, randomized 1:1, double blind, multicenter trial against placebo with a Bayesian design.

Eligibility criteria: any female patient scheduled for breast surgery with mastectomy and axillary node dissection indicated at the pre-surgical stage.

Specific aims: The purpose of this trial is to assess the efficacy of a single pre-surgical injection of pasireotide LAR 60 mg im in reducing the postoperative incidence of symptomatic lymphoceles following mastectomy with axillary node dissection for breast cancer. Patients are followed up for 4 weeks

Statistical methods: The statistical analysis will be carried out sequentially after observing the principal criterion (i.e. success is defined as a total volume of lymphocele following single or repeated aspiration ≤ 60 cc in the 28 days following surgery or a routine aspiration volume on the 28th day ≤ 120cc) of each patient included for each randomization group, with or without treatment.

It involves estimating the probability of a response in each group using a Bayesian design based on a beta-binomial model. With the Bayesian approach, the response rate in each group (πi) is considered as a random variable, with a priori density focused on the anticipated response rate of 80% in the group receiving treatment and 60% in the non-treatment group, which will be sequentially updated as the observations are made according to a so-called a posteriori law. Present accrual and target accrual: The sample size consists of a total of 90 patients with 45 patients in the active treatment group and 45 patients in the placebo one. To date more than 50% of the patients have been included.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT2-07-01.
OT3-01-15: Phase III Trial Evaluating the Addition of Bevacizumab to Endocrine Therapy as First-Line Treatment for Advanced Breast Cancer: The LEA Study.
Authors: De la Haba-Rodriguez JR , von Minckwitz G , Martín M , Morales S , Crespo C , Guerrero A , Anton-Torres A , Gil M , Muñoz M , Carrasco E , Rodríguez-Martin C , Porras I , Aktas B , Schoenegg W , Tio J , Mehta K , Loibl S , On Behalf of GEICAM and GBG
Published: June 2012

Background

Retrospective clinical data suggest that high vascular endothelial growth factor (VEGF) levels in breast tumors are associated with a decreased response to endocrine therapy. We designed the randomized phase III LEA study of first-line bevacizumab in combination with endocrine therapy, to address the hypothesis that anti-VEGF treatment can prevent resistance to endocrine therapy in patients with advanced breast cancer sensitive to such treatment.

Methods: Postmenopausal patients with evaluable locally recurrent or metastatic breast cancer, HER2−negative- and estrogen receptor (ER)-and/or progesterone receptor (PgR)-positive disease, and eligible to receive hormonal treatment are candidates for this study. Patients are randomized to receive letrozole 2.5mg daily or fulvestrant, 250mg every 4 weeks (Arm A) or the same hormonal therapy plus bevacizumab 15mg/kg every 3 weeks (Arm B). The primary objective is to compare progression-free survival (PFS) between the treatment arms. Secondary endpoints are overall survival, time to treatment failure, overall response rate, response duration, clinical benefit rate and safety. In total, 344 patients (172 in each treatment arm) will be needed to detect a hazard ratio of 0.69 (corresponding to a median PFS of 9 months in Arm A and 13 months in Arm B) with a power of 80% and a two-tailed log-rank test at 0.05. With an expected drop-out rate of 10%, 378 patients will be included. Efficacy analysis will be triggered after 270 events.

Results: Recruitment began in November 2007. To date, 348 patients have been included in the study in Spain (n=244) and Germany (n=104). We anticipate completing recruitment by September 2011. Baseline characteristics of the first 334 randomized patients are shown in the table.

Conclusions: LEA is the first study to explore the use of an anti-angiogenic drug in combination with endocrine therapy in the context of a phase III study.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT3-01-15.
OT3-01-16: A Phase 2 Study of Ridaforolimus (RIDA) and Dalotuzumab (DALO) in Estrogen Receptor Positive (ER+) Breast Cancer.
Authors: Lu BD , Blum JL , Cortes J , Rugo HS , Swanton C , Eaton L , Song Y , Zhang T , Ebbinghaus SW , Baselga J
Published: June 2012

Background: Activation of the PI3K/AKT/mTOR pathway is common in breast cancer. Preclinical studies indicate that the dual inhibition of IGFR and mTOR may be additive or synergistic and abrogates the feedback activation of AKT due to rapamycin analog mTOR inhibitors. A phase 1 study of the mTOR inhibitor RIDA and the anti-IGFR antibody DALO demonstrated that the combination was feasible and well-tolerated at doses that were nearly those used for the two single agents and with dose limiting toxicity of stomatitis, similar to RIDA as monotherapy. A preliminary signal of anti-tumor activity, including partial responses and prolonged progression free survival, was observed in ER+ breast cancer, especially in high proliferation tumors. This observation is supported by data from tumor profiling and preclinical data suggesting that ER+ high proliferation breast cancer may be responsive to the RIDA-DALO combination. Methods: This is a two-part, adaptive design study intended to first test the combination of RIDA-DALO against a standard agent, exemestane, for ER+ positive breast cancer that has progressed after aromatase inhibitors. The trial is a multi-center, international, randomized study with PFS as the primary endpoint. Patients (pts) are stratified into high and low proliferation strata based on baseline Ki67, and the low proliferation stratum is capped to ensure adequate enrollment of high proliferation pts. If Part A shows a PFS benefit for RIDA-DALO, Part B is intended to show the PFS benefit of the combination over the single agents by comparing RIDA-DALO to RIDA and DALO. Part B will be further adapted based on whether the PFS benefit in Part A is observed in all-comers or the high proliferation subset. Tumor tissue is collected for molecular profiling and analysis of intrinsic subtype, with an efficacy analysis based on classification of tumors using the genomic grade index (GGI) as an exploratory objective. This trial design is intended to establish proof of concept that RIDA-DALO can prolong PFS in ER+ breast cancer in all-comers or a high proliferation subset by Ki67, while efficiently addressing the development of two investigational agents in combination and leading to a two-arm Phase 3 design.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT3-01-16.
P1-01-08: Expression of Interleukin-15 (IL-15) and the IL-15 Receptor in Human Breast Cancer.
Authors: Sanders AJ , Ye L , Wei XQ , Mansel RE , Jiang WG
Published: June 2012

Introduction: Interleukin-15 (IL15) is a cytokine that influences activation and proliferation of T-lymphocytes. IL-15 is produced in the body leukocytes such as phagocytes and in many ways has similar immunoregulatory functions to IL-2 including stimulation of NK cells and CD8(+) T cells. It has been suggested that IL-15 may increase the immunity to cancer cells and cancer cell's response to therapeutic agents. IL-15 has also been shown to be able to inhibit tumour growth in vivo. However, the expression profile of IL-15 and IL-15 receptor (IL-15) in solid tumours including human breast cancer is not clear. The present study investigated the expression profile of both IL-15 and IL-15R in human breast cancer and deduced a clinical and pathological relevance with breast cancer.

Methods: Immunohistochemical methods were used to detect IL-15 and IL-15RA in mammary tissues. IL-15 and IL-15RA transcripts were analysed using real-time quantitative PCR method. Levels of IL-15 and IL-15RA were compared in normal and tumour tissues as well as against tumour staging, nodal status, disease progression and clinical outcome after a 10-year followup.

Results: Both IL-15 and IL-15RA were detectable in mammary tissues and were seen in both epithelial cells and infiltrating cells. Node positive tumours had low levels of IL-15 compared with node negative tumours (21.7±10 vs 103±46, respectively). Late stage tumour also had lower levels of IL-15 (95±43, 31±15, 3.7±2 and 1.3±1.15 for stage I, II, III and IV tumours respectively. p=0.036 and p=0.032, stage-II and Stage-III vs stage-I). Patients with metastatic disease (10.3±3) and patients died of breast cancer related conditions (8.5±6) had markedly low levels of IL-15 when compared with those who were disease free (54.7±25). The disease free survival time for patients with low levels IL-15 was 126 (114-138, 95%CI) months, compared with 139 (131-148) months for those with high levels of IL-15. Despite the reduced expression of IL-15 in aggressive tumours, expression of IL-15 receptor, IL-15RA, did not display a significant change and failed to showed a link with nodal status, tumour staging and clinical outcome.

Conclusions: Interleukin-15, an immuoregulatory cytokine, has an aberrant expression in human breast cancer. Low levels of IL-15, but not IL-15 receptor, is associated with the aggressiveness and disease progression of breast cancer. Together with reported effect of IL-15 on NK cells and other anti-tumour lymphocytes, IL-15 appears to be a useful therapeutic option.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-01-08.