bluuebunny/crossref_metadata_2025_split huggingface dataset:
Involvement of Lyn and the Atypical Kinase SgK269/PEAK1 in a Basal Breast Cancer Signaling Pathway
Authors: Croucher David R. , Hochgräfe Falko , Zhang Luxi , Liu Ling , Lyons Ruth J. , Rickwood Danny , Tactacan Carole M. , Browne Brigid C. , Ali Naveid , Chan Howard , Shearer Robert , Gallego-Ortega David , Saunders Darren N. , Swarbrick Alexander , Daly Roger J. 
Published: February 2013

Abstract
Basal breast cancer cells feature high expression of the Src family kinase Lyn that has been implicated in the pathogenicity of this disease. In this study, we identified novel Lyn kinase substrates, the most prominent of which was the atypical kinase SgK269 (PEAK1). In breast cancer cells, SgK269 expression associated with the basal phenotype. In primary breast tumors, SgK269 overexpression was detected in a subset of basal, HER2-positive, and luminal cancers. In immortalized MCF-10A mammary epithelial cells, SgK269 promoted transition to a mesenchymal phenotype and increased cell motility and invasion. Growth of MCF-10A acini in three-dimensional (3D) culture was enhanced upon SgK269 overexpression, which induced an abnormal, multilobular acinar morphology and promoted extracellular signal–regulated kinase (Erk) and Stat3 activation. SgK269 Y635F, mutated at a major Lyn phosphorylation site, did not enhance acinar size or cellular invasion. We show that Y635 represents a Grb2-binding site that promotes both Stat3 and Erk activation in 3D culture. RNA interference–mediated attenuation of SgK269 in basal breast cancer cells promoted acquisition of epithelial characteristics and decreased anchorage-independent growth. Together, our results define a novel signaling pathway in basal breast cancer involving Lyn and SgK269 that offers clinical opportunities for therapeutic intervention. Cancer Res; 73(6); 1969–80. ©2012 AACR.
FOXC2 Expression Links Epithelial–Mesenchymal Transition and Stem Cell Properties in Breast Cancer
Authors: Hollier Brett G. , Tinnirello Agata A. , Werden Steven J. , Evans Kurt W. , Taube Joseph H. , Sarkar Tapasree Roy , Sphyris Nathalie , Shariati Maryam , Kumar Sreedevi V. , Battula Venkata L. , Herschkowitz Jason I. , Guerra Rudy , Chang Jeffrey T. , Miura Naoyuki , Rosen Jeffrey M. , Mani Sendurai A. 
Published: February 2013

Abstract
Resistance to chemotherapy and metastases are the major causes of breast cancer-related mortality. Moreover, cancer stem cells (CSC) play critical roles in cancer progression and treatment resistance. Previously, it was found that CSC-like cells can be generated by aberrant activation of epithelial–mesenchymal transition (EMT), thereby making anti-EMT strategies a novel therapeutic option for treatment of aggressive breast cancers. Here, we report that the transcription factor FOXC2 induced in response to multiple EMT signaling pathways as well as elevated in stem cell-enriched factions is a critical determinant of mesenchymal and stem cell properties, in cells induced to undergo EMT- and CSC-enriched breast cancer cell lines. More specifically, attenuation of FOXC2 expression using lentiviral short hairpin RNA led to inhibition of the mesenchymal phenotype and associated invasive and stem cell properties, which included reduced mammosphere-forming ability and tumor initiation. Whereas, overexpression of FOXC2 was sufficient to induce CSC properties and spontaneous metastasis in transformed human mammary epithelial cells. Furthermore, a FOXC2-induced gene expression signature was enriched in the claudin-low/basal B breast tumor subtype that contains EMT and CSC features. Having identified PDGFR-β to be regulated by FOXC2, we show that the U.S. Food and Drug Administration-approved PDGFR inhibitor, sunitinib, targets FOXC2-expressing tumor cells leading to reduced CSC and metastatic properties. Thus, FOXC2 or its associated gene expression program may provide an effective target for anti-EMT-based therapies for the treatment of claudin-low/basal B breast tumors or other EMT-/CSC-enriched tumors. Cancer Res; 73(6); 1981–92. ©2012 AACR.
Procollagen Lysyl Hydroxylase 2 Is Essential for Hypoxia-Induced Breast Cancer Metastasis
Authors: Gilkes Daniele M. , Bajpai Saumendra , Wong Carmen C. , Chaturvedi Pallavi , Hubbi Maimon E. , Wirtz Denis , Semenza Gregg L. 
Published: February 2013

Abstract
Metastasis is the leading cause of death among patients who have breast cancer. Understanding the role of the extracellular matrix (ECM) in the metastatic process may lead to the development of improved therapies to treat patients with cancer. Intratumoral hypoxia, found in the majority of breast cancers, is associated with an increased risk of metastasis and mortality. We found that in hypoxic breast cancer cells, hypoxia-inducible factor 1 (HIF-1) activates transcription of the PLOD1 and PLOD2 genes encoding procollagen lysyl hydroxylases that are required for the biogenesis of collagen, which is a major constituent of the ECM. High PLOD2 expression in breast cancer biopsies is associated with increased risk of mortality. We show that PLOD2 is critical for fibrillar collagen formation by breast cancer cells, increases tumor stiffness, and is required for metastasis to lymph nodes and lungs. Mol Cancer Res; 11(5); 456–66. ©2013 AACR.
The Greek Translator of ExodusInterpres (translator) and Expositor (interpretor) His Treatment of Theophanies
Authors: Perkins Larry 
Published: February 2013

Abstract
Scholars have noted the various strategies used in Greek Exodus to ensure conformity in the narrative with Yahweh’s warning (Exod 33:20) “No one shall see me and live.” Close examination of five “theophanies,” the rendering of the Hebrew verb יעד when Yahweh is subject, and the rendering of the Hebrew expression “see the face of Yahweh” indicates that the translator carefully communicated in the target text compliance of Moses and others with the principle expressed in Exod 33:20. In some cases the translator may be following a different Hebrew Vorlage, but in most cases the text suggests the translator shapes the Greek text to conform with the Exod 33:20 axiom. That this tendency occurs in at least three different types of situations within Greek Exodus indicates that the translator is both interpres and expositor.
Neuropathological effect of dimethyl disulfide on neurons of the desert locust Schistocerca gregaria
Authors: Essawy Amina E , Gaaboub Ibrahim A , Abdel-Moneim Ashraf M , El-Sayed Soad A 
Published: February 2013

Botanical insecticides have introduced a new concept in insecticide research. In response to insect attacks, some plants can release volatile compounds that alter insect metabolism and nervous system activity. In the present study, changes in the electrical activity of chemoreceptors and alteration of the fine structure of metathoracic ganglia of desert locust were examined after acute exposure to dimethyl disulfide (DMDS), a sulfur compound released from Allium porrum. Animals were exposed to 1/4 LC50 of DMDS (0.375 μl/L air) and electrophysiological and electron-microscopical studies were carried out. Application of DMDS showed an increase in the activity of deterrent cells present in tarsal chemosensilla of locust. On the other hand, evident degenerative changes in the neurons, neuroglia, neuropile and synaptic vesicles were observed in the metathoracic ganglia of DMDS-treated animals. These findings revealed that pest control using DMDS might be feasible and future work is highly recommended in this respect.
Clinical Update on Genetic and Autoimmune Biomarkers in Pediatric Diabetes
Authors: O’Connor M. Rebecca , Doorenbos Ardith , Voss Joachim 
Published: February 2013

Purpose: The purpose of this clinical update is to review the etiology of diabetes types affecting youth under 20 and describe diabetes-related genetic and autoimmune biomarkers based on the most recent literature. This information will support diabetes care providers’ efforts to better explain the complex topic to patients and families. Method: A PubMed search identified 396 reviews published from 2008 to 2011 that included the topics of etiology, epidemiology, genetics/epigenetics, pathogenesis, or immunology related to diabetes in youth. The current clinical update includes 19 of these. Results: The majority of youth under 20 years with diabetes have Type 1 diabetes. Other forms of the disease affecting this population include Type 2, monogenic, and secondary diabetes. Genetic and autoimmune biomarkers can help determine the risk and diagnosis of both Type 1 and monogenic diabetes. An accurate diagnosis of diabetes type allows for determination of optimal treatment options. Conclusion: The complexity of determining etiology, risk, diagnosis, and treatment for diabetes in youth is increasing with the rate of related genetic and immunologic advances. Diabetes care providers must be able to explain the complex genetic and autoimmune biomarkers used in determining the risk of diabetes, diagnosis of the disease, and identification of treatment options to patients and families.
Antiproteinuric effect of angiotensin receptor blockers in normotensive patients with proteinuria: A meta-analysis of randomized controlled trials
Authors: Geng Deng-feng , Sun Wei-feng , Yang Li , En Ge , Wang Jing-feng 
Published: February 2013

Introduction: The objective of this article is to evaluate the antiproteinuric effect of angiotensin receptor blockers (ARBs) in normotensive patients with proteinuria. Materials and methods: We reviewed randomized controlled trials assessing ARBs treatment in patients with normotension and proteinuria. Data concerning the study design, patient characteristics, and outcomes were extracted. Ratio of means was calculated by using the generalized inverse variance method. Results: Eight trials involving 866 patients were included in this study. Compared with a control group, ARBs group was associated with a significant reduction in urinary protein excretion (ratio of means 0.53, 95% CI 0.44–0.64). Subgroup analysis shows that ARBs therapy resulted in a significant decrease in urinary protein excretion in diabetic patients with microalbuminuria or nondiabetic nephropathy with overt proteinuria (ratio of means 0.57, 95% CI 0.47–0.69 and 0.46, 95% CI 0.26–0.83, respectively), in a Western population or an Asian population (ratio of means 0.61, 95% CI 0.54–0.69 and 0.49, 95% CI 0.37–0.64, respectively), and in patients followed up for one to three months or three to 12 months (ratio of means 0.62, 95% CI 0.54–0.70 and 0.49, 95% CI 0.38–0.63, respectively). Conclusions: The data suggest that ARBs may have beneficial effects in preventing the progression of proteinuria in normotensive patients with renal disease.
Multiple-locus variable-number tandem-repeat analysis of Streptococcus pneumoniae and comparison with multiple loci sequence typing
Authors: van Cuyck Hélène , Pichon Bruno , Leroy Philippe , Granger-Farbos Alexandra , Underwood Anthony , Soullié Bruno , Koeck Jean-Louis 
Published: February 2013

Abstract

Background

Streptococcus pneumoniae infections remain a major cause of morbidity and mortality worldwide. The diversity of pneumococci was first evidenced by serotyping of their capsular polysaccharides, responsible of virulence, resolving into more than 93 serotypes. Molecular tools have been developed to track the emergence and the spread of resistant, hyper virulent or non-vaccine type clones, particularly DNA-based methods using genetic polymorphism. Pulsed-Field Gel Electrophoresis analysis (PFGE) and Multiple Loci Sequence Typing (MLST) are the most frequently used genotyping techniques for S. pneumoniae. MLST is based on sequence comparison of housekeeping genes clustering isolates within sequence types. The availability of genome sequence data from different S. pneumoniae strains facilitated the search for other class of genetic markers as polymorphic DNA sequences for a Multiple-Locus Variable-Number Tandem-Repeat Analysis (MLVA). This study aims at confirming the relevance of MLVA of S. pneumoniae, comparing MLST and MLVA performances when discriminating subgroups of strains belonging to the same Sequence Type (ST), and defining a restricted but universal set of MLVA markers that has at least the same discriminatory power as MLST for S. pneumoniae by applying marker sets used by different authors on 331 isolates selected in UK.

Results
A minimum spanning tree was built including the serotypes distribution and comparing MLVA and MLST results. 220 MLVA types were determined grouped in 10 Sequence Types (ST). MLVA differentiated ST162 in two clonal complexes. A minimal set was defined: ms 25 and ms37, ms17, ms19, ms33, ms39, and ms40 including two universal markers. The selection was based on MLVA markers with a Diversity Index >0.8 and a selection of others depending of the population tested and the aim of the study. This set of 7 MLVA markers yields strain clusters similar to those obtained by MLST.

Conclusions
MLVA can discriminate relevant subgroups among strains belonging to the same ST. MLVA offers the possibility to deduce the ST from the MLVA Type. It permits to investigate local outbreaks or to track the worldwide spread of clones and the emergence of variants.
Expression of LGR-5, MSI-1 and DCAMKL-1, putative stem cell markers, in the early phases of 1,2-dimethylhydrazine-induced rat colon carcinogenesis: correlation with nuclear β-catenin
Authors: Femia Angelo Pietro , Dolara Piero , Salvadori Maddalena , Caderni Giovanna 
Published: February 2013

Abstract

Background
Colon cancer stem cells may drive carcinogenesis and account for chemotherapeutic failure. Although many markers for these cells have been proposed, there is no complete agreement regarding them, nor has their presence in the early phases of carcinogenesis been characterized in depth.

Methods
The expression of the putative markers LGR-5 (leucine-rich-repeat-containing G-protein-coupled receptor 5), MSI-1 (Musashi-1) and DCAMKL-1 (doublecortin and calcium/calmodulin-dependent protein kinase-like-1) was studied in normal colon mucosa (NM), in the precancerous lesions Mucin Depleted Foci (MDF) and in macroscopic tumours (adenomas) of 1,2-dimethylhydrazine-treated rats. Co-localization between these markers and nuclear β-catenin (NBC), an attributed feature of cancer stem cells, was also determined. Moreover, since PGE2 could increase NBC, we tested whether short-term treatment with celecoxib, a COX-2 inhibitor (2 weeks, 250 ppm in the diet) could reduce the expression of these markers.

Results
LGR-5 expression in NM was low (Labelling Index (LI): 0.22±0.03 (means±SE)) with positive cells located mainly at the base of the crypts. Compared to NM, LGR-5 was overexpressed in MDF and tumours (LI: 4.7±2.0 and 2.9±1.0 in MDF and tumours, respectively, P<0.01 compared to NM). DCAMKL-1 positive cells, distributed along the length of normal crypts, were reduced in MDF and tumours. Nuclear expression of MSI-1, located mainly at the base of normal crypts, was not observed in MDF or tumours. In both MDF and tumours, few cells co-expressed LGR-5 and NBC (LI: 1.0±0.3 and 0.4±0.2 in MDF and tumours, respectively). Notwithstanding the lower expression of DCAMKL-1 in tumours, the percentage of cells co-expressing DCAMKL-1 and NBC was higher than in NM (LI: 0.5±0.1 and 0.04±0.02 in tumours and NM, respectively). MSI-1 and NBC co-localization was not observed. Celecoxib did not reduce cells co-expressing LGR-5 and NBC.

Conclusions
Based on its prevalent localization at the base of normal crypts, as expected for stem cells, and on the overexpression in precancerous lesions and tumours, we support LGR-5, but not MSI-1 or DCAMKL-1, as putative neoplastic stem cell marker. In both MDF and tumours, we identified LGR-5-positive cells co-expressing NBC which could be a subpopulation with the highest stem cell features.
The potential prognostic value of connexin 26 and 46 expression in neoadjuvant-treated breast cancer
Authors: Teleki Ivett , Krenacs Tibor , Szasz Marcell A , Kulka Janina , Wichmann Barna , Leo Cornelia , Papassotiropoulos Barbel , Riemenschnitter Cosima , Moch Holger , Varga Zsuzsanna 
Published: February 2013

AbstractBackgroundSeveral classification systems are available to assess pathological response to neoadjuvant chemotherapy in breast cancer, but reliable biomarkers to predict the efficiency of primary systemic therapy (PST) are still missing. Deregulation of gap junction channel forming connexins (Cx) has been implicated in carcinogenesis and tumour progression through loss of cell cycle control. In this study we correlated Cx expression and cell proliferation with disease survival and pathological response to neoadjuvant chemotherapy in breast cancers using existing classification systems.MethodsThe expression of Cx26, Cx32, Cx43, Cx46 and Ki67 was evaluated in 96 breast cancer patients prior to and after neoadjuvant chemotherapy using duplicate cores in tissue microarrays (TMA). Cx plaques of <1μm were detected with multilayer, multichannel fluorescence digital microscopy. Current classifications to assess residual tumour burden after primary systemic therapy included the EWGBSP, CPS-EG, Miller-Payne, Sataloff and NSABP systems.ResultsIn our cohort dominated by hormone receptor (ER/PR) positive and HER2 negative cases, only the CPS-EG classification showed prognostic relevance: cases with scores 1–2 had significantly better overall survival (p=0.015) than cases with scores 3–5. Pre-chemotherapy Cx43 expression correlated positively with hormone receptor status both before and after chemotherapy and had a negative correlation with HER2 expression pre-chemotherapy. There was a positive correlation between Cx32 and HER2 expression pre-chemotherapy and between Cx32 and Ki67 expression post-chemotherapy. A negative correlation was found between post-chemotherapy Cx46 and Ki67 expression. Decreased post-chemotherapy Cx26 expression (<5%) statistically correlated with better overall survival (p=0.011). Moderate or higher Cx46 expression (>20%) pre- and post-chemotherapy correlated with significantly better survival in the intermediate prognostic subgroups of EWGBSP TR2b (ppre-chemo=0.006; Sataloff TB (ppre-chemo=0.005; ppost-chemo=0.029) and in Miller-Payne G3 (ppre-chemo=0.002; ppost-chemo=0.012) classifications. Pre-chemotherapy, Cx46 expression was the only marker that correlated with overall survival within these subgroups.ConclusionOur results suggest that Cx46 and Cx26 expression in breast cancer may improve the assessment of pathological response and refine intermediate prognostic subgroups of residual tumour classifications used after neoadjuvant chemotherapy.
HIV testing practices among black primary care physicians in the United States
Authors: Wong Eric Y , Jordan Wilbert C , Malebranche David J , DeLaitsch Lori L , Abravanel Rebecca , Bermudez Alisha , Baugh Bryan P 
Published: February 2013

Abstract

Background
The Centers for Disease Control and Prevention recommends routine HIV testing in all healthcare settings, but it is unclear how consistently physicians adopt the recommendation. Making the most of each interaction between black physicians and their patients is extremely important to address the HIV health disparities that disproportionately afflict the black community. The goal of this survey-based study was to evaluate the perceptions and practices of black, primary care physicians regarding HIV testing.

Methods
A physician survey was administered at the 2010 National Medical Association Annual Convention, via online physician panels, and by email. Physician eligibility criteria: black race; practicing at least 1 year in the US; practice comprised of at least 60% adults and 20% black patients. Contingency tables and ordinary least squares regression were used for comparisons and statistical analyses. A Chi-square test compared percentages of physicians who gave a particular response and a t-test compared the means of values provided by physicians.

Results
Physicians over-estimated HIV prevalence and believed that HIV is a crisis in the black community, yet reported that only 34% of patients were HIV tested in the past year. Physicians reported that 67% of those patients tested did so due to a physician recommendation. Physicians who were younger, female, obstetricians/gynecologists, and had a higher proportion of black, low-socioeconomic status, and Medicaid patients reported higher testing rates. Most testing was risk-based rather than routine, and three of the five most commonly reported barriers to testing were related to disease stigma and perceived value judgments. Physicians reported that in-office patient informational materials, increased media attention, additional education and training on HIV testing, government mandates requiring routine testing, and accurate pre-packed tests would most help them test more frequently for HIV.

Conclusions
In this sample of black, primary care physicians, HIV testing practices differed according to physician characteristics and practice demographics, and overall reported testing rates were low. More physician education and training around testing guidelines is needed to enable more routine testing, treatment, and long-term management of patients with HIV.
Retroperitoneoscopic donor nephrectomy with a gel-sealed hand-assist access device
Authors: Arai Kei , Nishiyama Tsutomu , Hara Noboru , Kasahara Takashi , Saito Kazuhide , Takahashi Kota 
Published: February 2013

Abstract

Background
The hand-assisted technique enables the rapid extraction of the graft, shortening the warm ischemia time (WIT), and the retroperitoneoscopic approach is potentially associated with a less incidence of postoperative ileus in donor nephrectomy for living kidney transplantation. The aim of this study was to assess the efficacy and safety of retroperitoneoscopic donor nephrectomy with a gel-sealed hand-assist access device (GelPort), which is a wound sealing device that permits the access of the hand to the surgical field, free trocar site choice within it, and rapid conversion to open surgery if necessary, while preserving the pneumoperitoneum/pneumoretroperitoneum.

Methods
Seventy-five consecutive donors receiving this procedure were retrospectively studied. A 2-cm skin incision was made at the midpoint between the tip of the 12th rib and superior border of the iliac bone in the midaxillary line, through which retroperitoneal space was made. Preperitoneal wound with a 6 – 7-cm pararectal incision in the upper abdominal region was connected to the retroperitoneal space. A GelPort was put inside the pararectal surgical wound. The principle was pure retroperitoneoscopic surgery; hand-assist was applied for retraction of the kidney in the renal vessel control and graft extraction.

Results
The mean operation time including waiting time for recipient preparation was 242.2±37.0 (range: 214.0–409.0) min, and the mean amount of blood loss was 164.3±146.6 (range: 10.0–1020.0) ml. The mean WIT was 2.8±1.0 (range: 1.0–6.0) min. The shortage of renal vessels or ureter was observed in none of the grafts. No donor experienced blood transfusion, open conversion, or injury of other organs. Blood loss was greater in patients with body mass index (BMI) of 25 kg/m2 or higher than in those with BMI of <25 kg/m2 (218.4±98.8 vs. 154.8±152.1 ml, P=0.031). No donor had postoperative ileus or reported wound pain leading to decreased activity of daily life or wound cosmetic problem.

Conclusions
Retroperitoneoscopic hand-assisted donor nephrectomy with the mentioned approach was suggested to be a feasible option without compromising safety, although further improvement in surgical techniques is warranted.