bluuebunny/crossref_metadata_2025 huggingface dataset:
SIZE EFFECT ON THE PERMEABILITY AND SHEAR INDUCED FLOW ANISOTROPY OF FRACTAL ROCK FRACTURES
Authors: HUANG NA , JIANG YUJING , LIU RICHENG , XIA YUXUAN
Published: February 2018

The effect of model size on fluid flow through fractal rough fractures under shearing is investigated using a numerical simulation method. The shear behavior of rough fractures with self-affine properties was described using the analytical model, and the aperture fields with sizes varying from 25 to 200[Formula: see text]mm were extracted under shear displacements up to 20[Formula: see text]mm. Fluid flow through fractures in the directions both parallel and perpendicular to the shear directions was simulated by solving the Reynolds equation using a finite element code. The results show that fluid flow tends to converge into a few main flow channels as shear displacement increases, while the shapes of flow channels change significantly as the fracture size increases. As the model size increases, the permeability in the directions both parallel and perpendicular to the shear direction changes significantly first and then tends to move to a stable state. The size effects on the permeability in the direction parallel to the shear direction are more obvious than that in the direction perpendicular to the shear direction, due to the formation of contact ridges and connected channels perpendicular to the shear direction. The variances of the ratio between permeability in both directions become smaller as the model size increases and then this ratio tends to maintain constant after a certain size, with the value mainly ranging from 1.0 to 3.0.
Ordered Rate Constitutive Theories for Non-Classical Thermoviscoelastic Fluids Incorporating Internal and Cosserat Rotation Rates
Authors: Surana K. S. , Joy A. D. , Reddy J. N.
Published: February 2018

This paper considers conservation and balance laws for non-classical fluent continua in the presence of internal rotation rates due to the velocity gradient tensor and the rotation rates due to Cosserat rotations. In these balance laws, the internal rotation rates are completely defined as functions of the velocity gradient tensor, but the Cosserat rotation rates are additional three degrees of freedom at each material point. When these rotation rates are resisted by the deforming continua, conjugate moments are created. For thermoviscoelastic fluent continua, these result in additional dissipation mechanism as well as rheology. This paper presents a thermodynamically consistent derivation of constitutive theories for such fluids based on the entropy inequality in conjunction with the representation theorem using integrity, i.e., complete basis. Material coefficients are derived and discussed. The constitutive theories are presented in the absence as well as presence of the balance of moments of moments as a balance law and are compared with the classical continuum theories. Retardation moduli corresponding to the Cauchy stress tensor, both symmetric and antisymmetric, as well as the symmetric and antisymmetric Cauchy moment tensors are derived. The constitutive theories presented in this paper are ordered rate theories. These incorporate convected time derivatives of the strain tensor up to order [Formula: see text] and the convected time derivatives of the stress and moment tensors up to certain orders. Simplified forms of the constitutive theories are also derived. It is shown and concluded that the constitutive theories for thermoviscoelastic fluids based on classical continuum theory such as Maxwell model, Oldroyd-B model, Giesekus model, etc., are all a subset of the constitutive theories presented in this paper for non-classical physics. Both compressible and incompressible thermoviscoelastic fluids are considered.
An Inverse Analysis-Based Optimal Selection of Cohesive Zone Model for Metallic Materials
Authors: Zhao Guanghui , Li Ju , Zhang Y. X. , Liang Zheng , Yang Chunhui
Published: February 2018

Five different cohesive zone models (CZMs), including bilinear, polynomial, trapezoidal, exponential, and PPR (Park–Paulino–Roesler) models, which are commonly used in simulating fracture failure of metallic materials, are evaluated in this paper. The cohesive parameters of these CZMs are determined by an inverse analysis based on the modified Levenberg–Marquardt method. A finite element (FE) model is developed by employing these CZMs and used to predict fracture behaviors of steel grade 120, which is frequently used for the tool joints of drill pipes. Tensile and fracture tests are conducted to determine material properties and fracture behaviors of the steel grade 120, and the fracture behavior obtained from the experiment is used to determine the CZM parameters and validate the FE model. It is found that the five CZMs, with the cohesive parameters determined by the inverse analysis, can be used to simulate the ductile fracture process of the steel, and that among the five CZMs, the exponential CZM provides the closest results to the experimental data.
Interactions of an Oscillating Rectangular Membrane with a Compressible Fluid
Authors: Gascón-Pérez Manuel
Published: February 2018

Interaction of an oscillating membrane with a fluid is important because the wide variety of technological applications. A boundary element method has been employed for the analysis of a vibrating rectangular membrane in contact with a compressible fluid at rest. The deformation modes of the membrane correspond to the vacuum case. For the calculation of the pressure jump over the membrane, the Helmholtz’s integral equation for the fluid pressure is employed taking into account the fluid-membrane interface boundary condition. Considering the membrane equation and applying a collocation method, the natural frequencies of the interacting system are obtained. The influence of various parameters such as aspect ratio, fluid density and membrane dimension on these frequencies is evaluated. Furthermore, the influence of the wave number on the fluid mass coefficient and the acoustic damping ratio are evaluated. The validity of the method is deduced when comparing the results obtained by other authors and theories.
Interactive laboratory classes enhance neurophysiological knowledge in Thai medical students
Authors: Wongjarupong Nicha , Niyomnaitham Danai , Vilaisaktipakorn Pitchamol , Suksiriworaboot Tanawin , Qureshi Shaun Peter , Bongsebandhu-phubhakdi Saknan
Published: February 2018

Interactive laboratory class (ILC) is a two-way communication teaching method that encourages students to correlate laboratory findings with materials from lectures. In Thai medical education, active learning methods are uncommon. This paper aims to establish 1) if ILCs would effectively promote physiology learning; 2) if effectiveness would be found in both previously academically high-performing and low-performing students; and 3) the acceptability of ILCs to Thai medical students as a novel learning method. Two hundred seventy-eight second-year medical students were recruited to this study. We conducted three ILC sessions, which followed corresponding lectures. We carried out multiple-choice pre- and post-ILC assessments of knowledge and compared by repeated-measures ANOVA and unpaired t-test. Subgroup analysis was performed to compare high-performance (HighP) and low-performance (LowP) students. After the ILCs, participants self-rated their knowledge and satisfaction. Post-ILC test scores increased significantly compared with pre-ILC test scores in all three sessions. Mean scores of each post-ILC test increased significantly from pre-ILC test in both LowP and HighP groups. More students self-reported a “very high” and “high” level of knowledge after ILCs. Most students agreed that ILCs provided more discussion opportunity, motivated their learning, and made lessons more enjoyable. As an adjunct to lectures, ILCs can enhance knowledge in medical students, regardless of previous academic performance. Students perceived ILC as useful and acceptable. This study supports the active learning methods in physiology education, regardless of cultural context.
Digital chalk-talk videos improve knowledge and satisfaction in renal physiology
Authors: Roberts John K. , Chudgar Saumil M. , Engle Deborah , McClain Elizabeth K. , Jakoi Emma , Berkoben Michael , Lehrich Ruediger W.
Published: February 2018

The authors began a curriculum reform project to improve the experience in a Renal Physiology course for first-year medical students. Taking into account both the variety of learning preferences among students and the benefits of student autonomy, the authors hypothesized that adding digital chalk-talk videos to lecture notes and live lectures would improve student knowledge, course satisfaction, and engagement. The authors measured performance on the renal physiology exam before (the traditional curriculum) and for 2 yr after implementation of the new curriculum. During the traditional and subsequent years, students took a Q-sort survey before and after the Renal Physiology course. Satisfaction was assessed based on ranked statements in the Q sort, as well as through qualitative analysis of student commentary. Compared with the traditional curriculum, mean scores on the renal physiology final exam were higher after implementation of the new curriculum: 65.3 vs. 74.4 ( P < 0.001) with year 1 and 65.3 vs. 79.4 ( P < 0.001) in the second year. After the new curriculum, students were more likely to agree with the statement, “I wish other courses were taught like this one.” Qualitative analysis revealed how the video-based curriculum improved student engagement and satisfaction. Adding digital chalk-talk videos to a traditional Renal Physiology course that included active learning led to improved exam performance and high levels of student satisfaction. Other preclinical courses in medical school may benefit from such an intervention.
Early versus late cardiac remodeling during right ventricular pressure load and impact of preventive versus rescue therapy with endothelin-1 receptor blockers
Authors: Ramos Sara Roldan , Pieles Guido , Sun Mei , Slorach Cameron , Hui Wei , Friedberg Mark K.
Published: February 2018

Pulmonary artery banding (PAB) causes right ventricular (RV) dysfunction, biventricular fibrosis, and apoptosis, which are attenuated by endothelin-1 receptor blockade (ERB). Little is known about the time course of remodeling and whether early versus late ERB confers improved outcome. PAB was performed in five groups of rabbits: Shams, 3-wk PAB (3W), 6-wk PAB (6W), 6-wk PAB + ERB administered from day 1 (6WERB1), and 6-wk PAB + ERB administered from day 21 (6WERB21). Biventricular development of profibrotic molecular signaling, fibrosis, apoptosis, and conductance catheter and echocardiography function were studied. Thirty-three rabbits [ n = 6–7 per group; 3.00 (0.23) kg, mean (SD)] developed half to full systemic RV pressures. Biventricular profibrotic signaling and collagen deposition [RV collagen: Shams 3.8 (0.58) vs. 3W 8.69 (2.52) vs. 6W 8.83 (4.02)%, P < 0.005] and apoptosis [RV: Shams 8.32 (3.2) vs. 3W 55.95 (47.55) vs. 6W 38.85 (17.26) apoptotic cells per microfield, P < 0.0005] increased with PAB. Early and late ERB attenuated fibrosis [RV: 6WERB1 5.55 (1.18), 6WERB21 5.63 (0.72)%] and apoptosis [RV: 6WERB1 11.1 (5.25), 6WERB21 20.24 (7.16) apoptotic cells per microfield, P < 0.0001 vs. 6W]. RV dimensions progressively increased at 3W and 6W and decreased with early ERB [end-diastolic dimensions: Shams 0.4 (0.13) vs. 3W 0.55 (0.78) vs. 6W 0.78 (0.25) vs. 6WERB1 0.71 (0.26) vs. 6WERB21 0.49 (0.23) cm, P < 0.05]. Despite increased RV contractility with PAB [RV end-systolic pressure-volume relationship: Shams 3.76 (1.76) vs. 3W 12.21 (3.44) vs. 6W 19.4 (6.88) mmHg/ml], biventricular function and cardiac output [Shams 196.1 (39.73) vs. 3W 149.9 (34.82) vs. 6W 151 (31.69) ml/min] worsened in PAB groups and improved with early and late ERB [6WERB1 202.8 (26.8), 6WERB21 194.8 (36.93) ml/min, P < 0.05 vs. PAB]. In conclusion, RV pressure overload induces early biventricular fibrosis, apoptosis, remodeling, and dysfunction that worsens with persistent RV hypertension. This remodeling is attenuated by early and late ERB.

NEW & NOTEWORTHY Our results in a rabbit model of progressive right ventricular (RV) pressure loading indicate that biventricular fibrosis, apoptosis, and dysfunction are already present when RV hypertension is reached at 3 wk of progressive pulmonary artery banding. These findings worsen with persistent RV hypertension to 6 wk and are attenuated with both early and late endothelin-1 receptor blockade, with some advantages to early therapy. These findings highlight the role of endothelin-1 in driving biventricular remodeling secondary to RV hypertension and suggest that early therapy with an endothelin-1 receptor blocker may be beneficial in attenuating biventricular remodeling but that late therapy is also effective.
Material Exchange and Migration between Pore Fluids and Sandstones during Diagenetic Processes in Rift Basins: A Case Study Based on Analysis of Diagenetic Products in Dongying Sag, Bohai Bay Basin, East China
Authors: Meng W. , Zeng J. H. , Cao Z. , Song G. Q. , Wang Y. S. , Teng J. L. , Guo Z.
Published: February 2018

The exchange and migration of basin materials that are carried by pore fluids are the essence of diagenesis, which can alter physical properties of clastic rocks as well as control formation and distribution of favorable reservoirs of petroliferous basins. Diagenetic products and pore fluids, resulting from migration and exchange of basin materials, can be used to deduce those processes. In this study, 300 core samples from 46 wells were collected for preparation of casting thin sections, SEM, BSE, EDS, inclusion analysis, and isotope analysis in Dongying Sag, Bohai Bay Basin, East China. Combined with geochemical characteristics of pore fluids and geological background of the study area, the source and exchange mechanisms of materials in the pore fluids of rift basins were discussed. It was revealed that the material exchange of pore fluids could be divided into five stages. The first stage was the evaporation concentration stage during which mainly Ca2+, Mg2+, and CO32- precipitated as high-Mg calcites. Then came the shale compaction stage, when mainly Ca2+ and CO32- from shale compaction water precipitated as calcites. The third stage was the carboxylic acid dissolution stage featured by predominant dissolution of plagioclases, during which Ca2+ and Na+ entered pore fluids, and Si and Al also entered pore fluids and then migrated as clathrates, ultimately precipitating as kaolinites. The fourth stage was the organic CO2 stage, mainly characterized by the kaolinization of K-feldspar as well as dissolution of metamorphic lithic fragments and carbon cements. During this stage, K+, Fe2+, Mg2+, Ca2+, HCO3-, and CO32- entered pore fluids. The fifth stage was the alkaline fluid stage, during which the cementation of ferro-carbonates and ankerites as well as illitization or chloritization of kaolinites prevailed, leading to the precipitation of K+, Fe2+, Mg2+, Ca2+, and CO32- from pore fluids.
Determinants of Antenatal Healthcare Utilisation by Pregnant Women in Third Trimester in Peri-Urban Ghana
Authors: Akowuah Jones Asafo , Agyei-Baffour Peter , Awunyo-Vitor Dadson
Published: February 2018

Access to quality healthcare still remains a major challenge in the efforts at reversing maternal morbidity and mortality. Despite the availability of established maternal health interventions, the health of the expectant mother and the unborn child remains poor due to low utilisation of interventions. The study examined the socioeconomic determinants of antenatal care utilisation in peri-urban Ghana using pregnant women who are in their third trimester. Two-stage sampling technique was used to sample 200 pregnant women who were in their third trimester from the District Health Information Management System software. Well-structured questionnaire was the instrument used to collect data from respondents. Descriptive statistics and inferential statistics including binary logit regression model were used to analyse the data with the help of SPSS and STATA software. The results showed varying utilisation levels of ANC. From the regression result, age, household size, and occupational status were identified as the important socioeconomic determinants of antenatal care utilisation among the respondents. The important system factors which influence antenatal care utilisation by the respondents are distance to ANC, quality of service, and service satisfaction. The study concludes that socioeconomic and health system factors are important determinants of antenatal care utilisation. Stepping up of interventions aimed at improving the socioeconomic status and addressing health system and proximity challenges could be helpful in improving antenatal care utilisation by pregnant women in Ghana.
Carbon Nanoparticle‐Supported Pd Obtained by Solar Physical Vapor Deposition
Authors: Pascu Alexandru , Stanciu Elena Manuela , Croitoru Cătălin , Roată Ionut Claudiu , Tierean Mircea Horia
Published: February 2018

Palladium supported on carbon nanoparticles has been obtained on a specially designed ceramic catalyst, obtained by thermal spraying on a copper substrate, starting from Pd/C targets. Solar physical vapor deposition in argon, an environment‐friendly and energy‐efficient alternative to arc or chemical vapor deposition, has been employed as a means of target vaporization at CNRS‐PROMES facility in Odeillo, France. The obtained nanoparticles have a spherical‐porous morphology with diameters ranging from 50 to 120 nm and specific sorption areas of 50,000 m2/g. The XRD diffractograms indicate the presence of dominatingly crystalline short‐range ordered graphene oxide layers, in contrast with the amorphous Pd/C starting precursor. The presence of palladium (0.6% wt.) at the surface of the nanoparticles was proved by the EDX and XRD analyses, making the synthesized material useful in applications such as catalysis or gas sorption.
Early Postweaning Treatment with Dimethyl Fumarate Prevents Prenatal Dexamethasone‐ and Postnatal High‐Fat Diet‐Induced Programmed Hypertension in Male Rat Offspring
Authors: Lin Yu-Ju , Lin I-Chun , Yu Hong-Ren , Sheen Jiunn-Ming , Huang Li-Tung , Tain You-Lin
Published: February 2018

Prenatal dexamethasone (DEX) exposure, postnatal high‐fat (HF) intake, and oxidative stress are closely related to the development of hypertension. Nuclear factor erythroid‐derived 2‐related factor 2 (Nrf2) regulates oxidative stress. Dimethyl fumarate (DMF) reportedly activates Nrf2 and protects against oxidative stress damage. We examined a 4‐month‐old male rat offspring from five groups (n = 8 for each group): control, DEX (0.1 mg/kg i.p. from a gestational age of 16 to 22 days), HF (D12331 diet from weaning to 4 months of age), and DEX + HF, DEX + HF + DMF (50 mg/kg/day via gastric gavage for 3 weeks after weaning). We found that postnatal HF intake aggravated prenatal DEX‐induced hypertension in adult male offspring, which could be prevented by DMF treatment. The beneficial effects of DMF treatment include an increase in renal Nrf2 gene expression, reduction of oxidative stress, decrease in plasma asymmetric dimethylarginine (ADMA) and renal soluble epoxide hydrolase protein levels, increase in the l‐arginine‐to‐ADMA ratio, and activation of genes related to nutrient sensing and autophagy (e.g., Pparb, Pparg, Ppargc1a, Ulk1, and Atg5). In conclusion, better understanding of the impact of the Nrf2 signaling pathway in the two‐hit model will aid in protecting children exposed to antenatal corticosteroids and a postnatal HF diet from programmed hypertension.
Phylogenetic Analysis of Dengue Virus in Bangkalan, Madura Island, East Java Province, Indonesia
Authors: Sucipto Teguh Hari , Kotaki Tomohiro , Mulyatno Kris Cahyo , Churrotin Siti , Labiqah Amaliah , Soegijanto Soegeng , Kameoka Masanori
Published: February 2018

Dengue virus (DENV) infection is a major health issue in tropical and subtropical areas. Indonesia is one of the biggest dengue endemic countries in the world. In the present study, the phylogenetic analysis of DENV in Bangkalan, Madura Island, Indonesia, was performed in order to obtain a clearer understanding of its dynamics in this country. A total of 359 blood samples from dengue-suspected patients were collected between 2012 and 2014. Serotyping was conducted using a multiplex Reverse Transcriptase-Polymerase Chain Reaction and a phylogenetic analysis of E gene sequences was performed using the Bayesian Markov chain Monte Carlo (MCMC) method. 17 out of 359 blood samples (4.7%) were positive for the isolation of DENV. Serotyping and the phylogenetic analysis revealed the predominance of DENV-1 genotype I (9/17, 52.9%), followed by DENV-2 Cosmopolitan type(7/17, 41.2%)and DENV-3 genotype I(1/17, 5.9%). DENV-4 was not isolated. The Madura Island isolates showed high nucleotide similarity to other Indonesian isolates, indicating frequent virus circulation in Indonesia. The results of the present study highlight the importance of continuous viral surveillance in dengue endemic areas in order to obtain a clearer understanding of the dynamics of DENV in Indonesia.
Abstract BS1-2: Myeloid-derived suppressor cells: many facets of regulation of tumor progression
Authors: Gabrilovich DI
Published: February 2018

Tumor associated macrophages (TAM), myeloid derived suppressor cells (MDSC), represented by PMN-MDSC and M-MDSC, and dendritic cells (DC) are major components of tumor microenvironment playing critical role in tumor progression. There are now compelling evidence linking MDSC with negative clinical outcomes in many types of cancer. Therefore, these cells are attractive therapeutic targets. Recently, several therapeutic strategies have been developed that target MDSC in mouse animal models and in first clinical trials. Recent findings of selective targeting of MDSC in cancer patients using agonistic TRAIL receptor DR5 antibody will be discussed. In 16 patients with advanced solid tumors this antibody demonstrated selective depletion of MDSC without affecting populations of neutrophils, monocytes, or lymphocytes. Another therapeutic strategy involves histone deacetilase inhibitor – entinostat. Recent study in tumor-bearing mice revealed that entinostat slightly increased expansion and accumulation of granulocytic cells in tumors. However, in contrast to untreated mice, these cells lacked suppressive activity. This effect was associated with potent antitumor activity of combination of entinostat with check-point inhibitors. By studying the effect of CSF1R inhibitor in tumor-bearing mice we identified the complex network regulating different groups of myeloid cells in tumor microenvironment. This network involves tumor cells and cancer associated fibroblast and protect tumors from loss of individual component of myeloid cell compartment. We determined that this network is operational not only in mice but also in cancer patients. Targeting of this network dramatically enhance the effect of cancer therapy.

Citation Format: Gabrilovich DI. Myeloid-derived suppressor cells: many facets of regulation of tumor progression [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr BS1-2.
Abstract ES9-1: Androgen Receptor in breast cancer. When might it serve as a suitable target?
Authors: Richer JK
Published: February 2018

In the last decade it has become clear that androgen receptors (AR) are present in the normal breast and are even more widely expressed in breast cancer than estrogen or progesterone receptors (ER or PR). The majority of estrogen receptor positive (ER+) breast cancers and a subset of triple negative breast cancer (TNBC) express AR. AR has long served as an effective therapeutic target In prostate cancer and potent drugs have been developed that either bind to AR or inhibit enzymes involved in androgen synthesis. In women, the primary source of androgens is the adrenal gland. Fat cells convert androgens to estrogens via the enzyme aromatase, the target of aromatase inhibitors. The relative abundance of the various steroid hormone receptors and context can affect the behavior of the receptors. Indeed, the role of AR differs in the three main subtypes of breast cancer (ER+, HER2+ and TNBC) and can change with treatment or disease progression. For instance, ER+ primary breast cancers can increase expression of AR following treatment with anti-estrogens such as tamoxifen or aromatase inhibitors, such that recurrent disease (having been deprived of estrogen), is rendered more dependent on androgens and AR. In some TNBC, AR can substitute for ER to some degree, and such tumors are slower growing and therefore less responsive to chemotherapy and often overexpress HER2. These types of tumors may therefore be responsive to concurrent treatment with anti-androgen combined with chemotherapy or HER2 targeting agents, much as we do for ER+/HER2+ tumors. This lecture will summarize impactful preclinical studies and summarize results of recent and ongoing clinical trials targeting AR in breast cancer.

Citation Format: Richer JK. Androgen Receptor in breast cancer. When might it serve as a suitable target? [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr ES9-1.
Abstract OT2-01-01: Observational study of axilla treatment for breast cancer patients with 1 to 3 positive micrometastases or macrometastases in sentinel lymph nodes
Authors: Imoto S , Saito Oba M , Masuda N , Nagashima T , Wada N , Takashima T , Kitada M , Kawada M , Hayashida T , Taguchi T , Aihara T , Miura D , Toh U , Yoshida M , Sugae S , Yoneyama K , Matsumoto H , Jinno H , Sakamoto J
Published: February 2018

[Background] Axilla surgery in node-positive breast cancer is dramatically changing from axillary lymph node dissection (ALND) to sentinel node biopsy (SNB). From the results of ACOSOG Z0011, IBCSG23-01 and AMAROS trials, adjuvant therapy and regional node irradiation could reduce regional lymph node recurrence for sentinel node-positive breast cancer patients. However, optimal indication of SNB alone remains uncertain. Trial design: To evaluate the outcome of sentinel node-positive breast cancer patients, the Japanese Society for Sentinel Node Navigation Surgery (SNNS) conducted a prospective cohort study in 2013 (UMIN000011782, Jpn J Clin Oncol, p.876-9, 2014). [Eligibility criteria] For eligible patients, SNB was performed or scheduled after 1 January 2012. Then 1 to 3 positive micrometastases or macrometastases in sentinel lymph nodes are confirmed by histological or molecular diagnosis. Primary chemotherapy before or after SNB is also acceptable for registration. [Specific aims] The primary endpoint is the 5-year recurrence rate of regional lymph node in patients treated with SNB alone. The secondary endpoint is the 5-year overall survival rate of this cohort. Patients treated with SNB followed by ALND are also registered simultaneously to compare the prognosis. The propensity score matching (PSM) is used to make the distributions of baseline risk factors comparable. [Statistical method] Based on an estimated recurrence rate of 5% at 5 years among patients treated with SNB alone, 240 patients are needed to give a 80% power to reject the null hypothesis that the recurrence rate is 10% with a one-sided type I error rate of 2.5%. If we consider that some patients will be lost to follow-up or become ineligible, a total of 250 patients will be needed to comprise the sample. [Present accrual] Eight hundred and eighty patients who underwent SNB alone or SNB followed by ALND were registered from 27 participating institutes between 2013 and 2016. Data cleaning is being performed. Patient's background and PSM will be reported.

Citation Format: Imoto S, Saito Oba M, Masuda N, Nagashima T, Wada N, Takashima T, Kitada M, Kawada M, Hayashida T, Taguchi T, Aihara T, Miura D, Toh U, Yoshida M, Sugae S, Yoneyama K, Matsumoto H, Jinno H, Sakamoto J. Observational study of axilla treatment for breast cancer patients with 1 to 3 positive micrometastases or macrometastases in sentinel lymph nodes [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr OT2-01-01.
Abstract P1-01-03: Preclinical evidence that distant metastases occur via the lymphatic route
Authors: Leslie PL , Ghosh SK , Porrello A , Cooley BC , Pecot CV
Published: February 2018

Cancer that metastasizes beyond the lymph nodes is almost invariably terminal. Therefore, understanding how cancer metastasizes is a critical aspect to understanding and eventually preventing cancer spreading from tissue to tissue. A major question that remains controversial is whether cancer cells that metastasize to the LNs are able to physically leave the LNs to colonize distant tissues. Moreover, whether cancer cell metastasis between different tissues involves unique genes is a question that requires further research. Using the metastatic mouse breast carcinoma line 4T1 in an LN microinjection model, we provide evidence suggesting that cancer cells can indeed metastasize and colonize distant tissues after direct implantation into the LNs. Interestingly, direct comparison of distant tissue metastatic capability comparing LN-microinjected cells and tail vein-injected cells suggests that the lymphatic route of cancer cell spreading may be a more efficient mechanism of metastasis than the hematogenous route. Moreover, our comparative transcriptome analysis results suggest that LN metastases show unique gene expression profiles relative to the primary breast tumors and distant metastases. We identified several genes that are up- or down-regulated in an LN-specific manner and thus may play a role in metastasis to the LNs and beyond. Collectively, our results suggest that LN metastases constitute an active “staging site” from which breast cancer cells can further metastasize to distant sites. Furthermore, we identify a unique set of genes that may be involved in the breast cancer metastatic process, several of which are potentially targetable using currently available inhibitors.

Citation Format: Leslie PL, Ghosh SK, Porrello A, Cooley BC, Pecot CV. Preclinical evidence that distant metastases occur via the lymphatic route [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-01-03.
Abstract P1-03-12: The ratio of omega-3 to omega-6 PUFAs impact cancer cell phenotype in the tumor microenvironment
Authors: Winikka L , Quach D , Harlow B , Brenner A , Munoz N , Tiziani S , deGraffenried L
Published: February 2018

Background: Studies have shown that obesity is associated with a worse breast cancer prognosis. Besides the effect of different stages of diagnosis and co-morbidities, recent data from our published in vitro and retrospective studies suggests that this phenomenon may occur because the obese state promotes a more aggressive cancer phenotype through the cyclooxygenase (COX-2) pathway and its production of prostaglandin E2 (PGE2). The metabolization of omega-3 fatty acids decreases the production of PGE2, and have been shown to have potential benefit to cancer patients by decreasing inflammation-related signaling. Our previous clinical trial showed mixed results in the effect of omega-3 PUFA supplements on PGE2 production in post-menopausal obese women. This led us to the hypothesis that the ratio of omega-3 to omega-6 PUFAs have differential effects on cell types within the tumor microenvironment, impacting cancer cell phenotype.

Approach: In vitro experiments, including wound-healing assays to determine motility, and clonogenic assays to determine overall survival, were performed to determine if exposure to higher ratios of omega-6 to omega-3 fatty acids lead to a more aggressive cancer phenotype. MCF-7 breast cancer cells were treated with the following fatty acid ratios of omega-6 (arachidonic acid (AA)) to omega-3 (eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)): 46:1, 20:1, 10:1, and 1.3:1. The wound-healing assays showed greater motility with higher ratios of omega-6 to omega-3 fatty acids conditions and the clonogenic assays showed greater survival with the higher ratios.

Conclusion: These data indicate that lowering ratios of omega-6 to omega-3 fatty acids may lessen the aggressiveness of breast cancer cells and be beneficial to some patients. Studies are on-going to investigate the impact of PUFA ratios on cancer cell phenotype directly, including proliferation and invasion, as well as the indirect effects from modulation of the other cells within the tumor microenvironment, including the macrophages and adipocytes.

Citation Format: Winikka L, Quach D, Harlow B, Brenner A, Munoz N, Tiziani S, deGraffenried L. The ratio of omega-3 to omega-6 PUFAs impact cancer cell phenotype in the tumor microenvironment [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-03-12.
Abstract P1-13-02: Withdrawn
Authors: Guarneri V , Dieci MV , Bisagni G , Brandes AA , Frassoldati A , Cavanna L , Musolino A , Giotta F , Cavazzini G , Garrone O , Bertone E , Cagossi K , Nanni O , Ferro A , Donadio M , Aieta M , Zamagni C , Piacentini F , Maiorana A , Ragazzi M , Cucchi MC , Querzoli P , Orsi N , Curtarello M , Urso L , Amadori A , Orvieto E , Vicini R , Balduzzi S , D'Amico R , Conte P
Published: February 2018

This abstract was withdrawn by the authors.
Abstract P2-04-01: Withdrawn
Authors: Magnani L , Pruneri G , Patten DK , Corleone G , Győrffy B , Erdős E , Saiakhova A , Goddard K , Vingiani A , Shousha S , Pongor LS , Hadjiminas DJ , Schiavon G , Barry P , Palmieri C , Coombes RC , Scacheri P
Published: February 2018

This abstract was withdrawn by the authors.
Abstract P2-05-10: Withdrawn
Authors: Zaidi S , Spring LM , Malvarosa G , Habin KR , Le LP , Ellisen LW , Iafrate AJ , Haber DA , Bardia A
Published: February 2018

This abstract was withdrawn by the authors.
Abstract P2-11-17: Is post mastectomy radiotherapy contributive in pN0-1mi breast cancers patients? Results of a French multi-centric cohort
Authors: Forissier V , Tallet A , Cohen M , Classe J-M , Reyal F , Chopin N , Mazouni C , Gimbergues P , Daraï E , Colombo PE , Azuar P , Lambaudie E , Houvenaeghel G
Published: February 2018

Aim: To assess the value of Post-mastectomy radiation therapy (PMRT) in breast cancer patients with no or minimal lymph nodes involvement.

Materials and methods: We retrospectively analyzed a French multi-centric cohort of 4283 patients treated between 1980 and 2013, by mastectomy and axillary dissection with or without PMRT. Practices were analyzed according 3 treatment periods (1980-1999, 2000-2005; 2006-2013). The value of PMRT on loco-regional recurrence, disease-free survival, breast cancer specific survival and overall survival was assessed in pN0-1mi patients, using multivariate analyses (logistic regression and Cox model). It was subsequently assessed according to the number of clinicopathologic recurrence-risk factors, generating a prognostic index (f-PMRT index), in an attempt to isolate a pN0-1mi patients subgroup deriving benefit from PMRT. We tested the accuracy of the Cambridge-PMRT (c-PMRT) index in the discrimination of patients with significantly different outcomes, as well as the value of PMRT in each c-PMRT prognostic group.

Results: PMRT was considered in more than half pN0-1mi patients of our cohort. Whereas matching pN0-1mi patients according to the number of clinicopathologic recurrence-risk factors led to isolate a higher-risk subpopulation (≥ 3 RR factors), PMRT had no significant impact on patients' outcomes, on multivariate analysis. Whereas the Cambridge-PMRT index had the potential to discriminate 3 patient populations with significantly different outcomes, its use did not help to the decision making for PMRT.

Conclusion: Despite a large cohort, we failed to isolate a subgroup of early breast cancer patients suitable for PMRT, in the absence of lymph node involvement.

Citation Format: Forissier V, Tallet A, Cohen M, Classe J-M, Reyal F, Chopin N, Mazouni C, Gimbergues P, Daraï E, Colombo PE, Azuar P, Lambaudie E, Houvenaeghel G. Is post mastectomy radiotherapy contributive in pN0-1mi breast cancers patients? Results of a French multi-centric cohort [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-11-17.
Abstract P3-01-16: How hot is enough for accurate sentinel lymph node axillary staging in breast cancer?
Authors: Lee MH , Kang SH , Cho J
Published: February 2018

Purpose:

Sentinel lymph node (SLN) biopsy is a well-established procedure for staging of the axilla in early-stage breast cancer and has replaced axillary lymph node dissection as the standard of care in patients with clinically lymph node–negative axilla. No consensus exists about the number of sentinel lymph nodes (SLNs) that should be removed based on radioactivity counts in breast cancer, although the “10% rule” is often used. In order to determine the frequency with which the hottest SLN 'fails' to be pathologically positive, and to determine which criteria best define the radioactive lymph node to be removed, we reviewed and analyzed our cases in which more than one SLN was detected and where there was also at least one pathologically positive node.

Methods:

We retrospectively studied 1062 breast cancer patients who underwent lymphoscintigraphy by injection of radioactive colloid and SLN biopsy between 2006 and 2015, with intraoperative determination of radioactive counts of nodes by a gamma probe.

Results:

A total of 247 patients (23.3%) had more than 1 SLN removed (mean 2.29); 53 patients (21.5%) had nodal metastases. Of the node-positive patients, the hottest SLN was positive in 90.6% (48 of 53). The lowest radioactive count of a positive SLN was 32% of that of the hottest node.

Conclusions:

In our study, most positive SLNs had the highest radioactivity and the hottest lymph node was not the pathologically positive node only in 9.4 %. Our institutional experience indicates that to obtain an acceptable false-negative rate, nodes should be removed until the 10% rule is met.

Citation Format: Lee MH, Kang SH, Cho J. How hot is enough for accurate sentinel lymph node axillary staging in breast cancer? [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-01-16.
Abstract P3-03-05: Association between BRCA1 and BRCA2 mutations and survival in breast cancer patients according to molecular subtype
Authors: Tredan O , De Talhouet S , Peron J , Friedlaender A , Vuilleumier A , Viassolo V , Ayme A , Chappuis PO , Buisson A , Bonadona V , Bodmer A , Labidi-Galy SI
Published: February 2018

Background:

Germline mutations in BRCA1/BRCA2 genes increase the risk of breast and ovarian cancers. In ovarian cancer patients (pts) treated with platinum, BRCA1, and especially BRCA2, carriers have better survival than non-carriers. In breast cancer pts, BRCA1 carriers have higher response rate to neoadjuvant chemotherapy, however the benefit on survival remains unclear.

Patients and Methods:

A cohort study was conducted in France and Switzerland and consisted in 860 pts diagnosed with early breast cancer who underwent genetic screening for BRCA1/BRCA2 germline mutations and who received neo(adjuvant) chemotherapy. Disease-free survival (DFS) and Breast-cancer specific survival (BCSS) were analyzed according to BRCA1/BRCA2 mutations and breast cancer subtype (triple negative breast cancers (TNBC) vs non-TNBC).

Results:

One hundred and forty-three pts carried BRCA1 mutation; 88 had BRCA2 mutation; and 629 were non-carriers. Median age at diagnosis was 39 years; median follow-up was 4.8 years. Two hundred and fifty-three pts had TNBC (94 BRCA1, 14 BRCA2 and 145 non-carriers), and 607 had non-TNBC (49 BRCA1, 74 BRCA2 and 484 non-carriers). Among TNBC pts, BRCA2 mutations were associated with higher 5-years DFS (100% vs 71% for non-carriers and 80% for BRCA1 carriers; log-rank p=0.040), and BCSS (100% vs 78% for non-carriers and 92% for BRCA1 carriers; log-rank p=0.011). BRCA1 mutations were associated with higher 5-years DFS compared to non-carriers, but the association did not reach statistical significance (HR adjusted on nodal status=0.64; 95%CI 0.36-1.16, Wald test p=0.14). BRCA1 mutations were associated with an improved 5-years BCSS compared to non-carriers (HR adjusted on nodal status=0.38; 95%CI 0.16-0.87, Wald test p=0.022). In non-TNBC patients, BRCA1 or BRCA2 mutations were not associated with higher 5-years DFS (79% for BRCA1, 79% for BRCA2 carriers, and 80% for non-carriers; log-rank p=0.88) nor BCSS (94%, 92%, and 94% respectively; log-rank p=0.79).

Conclusions:

Among pts with TNBC, having BRCA germline mutation was associated with improved survival. In our cohort of TNBC pts, BRCA2 carriers did not present breast cancer relapse.

Citation Format: Tredan O, De Talhouet S, Peron J, Friedlaender A, Vuilleumier A, Viassolo V, Ayme A, Chappuis PO, Buisson A, Bonadona V, Bodmer A, Labidi-Galy SI. Association between BRCA1 and BRCA2 mutations and survival in breast cancer patients according to molecular subtype [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-03-05.
Abstract P3-06-04: Bcl-2 functional converters inhibit tumor growth and metastatic potential in zebrafish xenografts
Authors: Gamble J , Pearce M , Kopparapu P , Jang HS , Tanguay R , Greenwood J , Kolluri S
Published: February 2018

While potential therapies might have pronounced success in the simplified settings in cell culture medium, many drugs fail or underperform when cancer cells are encased in a complex 3D microenvironment. Although, rat and mouse models will continue to be the gold standard for in vivo data in drug discovery, zebrafish xenograft models have emerged as a powerful model that can quickly and efficiently deliver in vivo drug efficacy data before commitment to expensive and time consuming rodent models. We have discovered several compounds that work as B-cell lymphoma 2 (Bcl-2) functional converters and activate Bcl-2 into a killer instead of its native anti-apoptotic role. In this study, we use a zebrafish xenograft model to evaluate the ability of these compounds to inhibit xenograft tumor growth of Bcl-2 expressing cancer cells, including triple negative breast cancers. Live fluorescent imaging of cancer cells within zebrafish embryos revealed a decrease in cancer cell growth while under treatment of compounds. Furthermore, the agents that converted Bcl-2 into pro-apoptotic protein also inhibited the metastatic potential of the cancer cells. Therefore, this study demonstrates zebrafish xenograft techniques that can be used to quickly and efficiently obtain in vivo drug discovery data. Moreover, we report novel Bcl-2 functional converter compounds that can effectively reduce xenograft tumor growth and its ability to invade tissue in a living 3D environment and establish the role of Bcl-2 in cancer progression.

Citation Format: Gamble J, Pearce M, Kopparapu P, Jang HS, Tanguay R, Greenwood J, Kolluri S. Bcl-2 functional converters inhibit tumor growth and metastatic potential in zebrafish xenografts [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-06-04.
Abstract P3-08-09: Impact of gene-expression profiling in patients with early breast cancer when applied outside the guideline directed indication area
Authors: Schreuder K , Kuijer A , Rutgers EJTh , Smorenburg CH , Van Dalen T , Siesling S
Published: February 2018

Purpose

In Dutch guidelines gene expression profiles (GEP) are indicated in estrogen receptor positive early breast cancer patients in whom benefit of chemotherapy (CT) is controversial based on traditional prognostic factors alone. Aim of the current study is to assess the use and impact of GEP on administration of adjuvant CT in breast cancer patients who have according to national guidelines a clear indication to either use or withhold adjuvant chemotherapy (clinical high or low risk).

Methods

Clinical low- and high risk patients, according to Dutch breast cancer guidelines, diagnosed between 2011-2014 were selected from the Netherlands Cancer Registry (NCR). Influence of GEP use and GEP test result on CT administration was assessed with logistic regression.

Results

Overall, 26,425 patients were identified; 4.8% of patients with clinical low- risk (444/ 9,354), 7.5% of the patients with a clinical high-risk (1,281/ 17,071) received a GEP. GEP use was associated with a significantly increased odds of CT administration in clinical low-risk patients (OR=2.12 95%CI: 1.44-3.11). In clinical high-risk patients GEP use was associated with a decreased frequency of CT administration (OR=0.55, 95%CI: 0.48-0.63). Adherence to the GEP result was higher in clinical high-risk patients with a discordant GEP result as compared to clinical low-risk patients with a discordant GEP result: 71.7% vs. 52.2%, respectively.

Conclusion

GEP is frequently used outside the indicated area and significantly influenced the administration of adjuvant CT, although adherence to the test-result was limited.

Citation Format: Schreuder K, Kuijer A, Rutgers EJTh, Smorenburg CH, Van Dalen T, Siesling S. Impact of gene-expression profiling in patients with early breast cancer when applied outside the guideline directed indication area [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-08-09.