tbuckley/cabot-search huggingface dataset:
Neutrophils are a major source of the epithelial barrier disrupting cytokine oncostatin M in patients with mucosal airways disease
Authors: Kathryn L. Pothoven, James E. Norton, Lydia A. Suh, Roderick G. Carter, Kathleen E. Harris, Assel Biyasheva, Kevin Welch, Stephanie Shintani-Smith, David B. Conley, Mark C. Liu, Atsushi Kato, Pedro C. Avila, Qutayba Hamid, Leslie C. Grammer, Anju T. Peters, Robert C. Kern, Bruce K. Tan, Robert P. Schleimer
Journal: Journal of Allergy and Clinical Immunology (2016)
Metachronous contralateral breast cancer: An analysis of risk factors and prognosis in 42,670 women in Sweden.
Authors: V. Vichapat, H. Garmo, M. Holmqvist, L. Holmberg, G. Liljegren, F. Warnberg, M. Lambe, T. Fornander, J. Adolfsson, M. Lüchtenborg
Journal: Journal of Clinical Oncology (2011)

1568 Background: The number of breast cancer survivors is rising and therefore the number of women at risk of developing contralateral breast cancer (CBC). We analysed the risk of and prognosis after CBC in relation to tumour characteristics. Methods: In a cohort of 42,670 women diagnosed with primary breast cancer in Uppsala/Örebro and Stockholm regions in Sweden between 01/01/1992 and 12/31/2008, factors associated with the risk of developing metachronous CBC were assessed using Cox proportional hazard modelling. We also evaluated breast cancer-specific survival for women with CBC in comparison to women with unilateral breast cancer (UBC), where characteristics of the contralateral tumour were entered as time-dependent covariates. Results: Women aged < 50 at the initial cancer diagnosis had the highest incidence of CBC. We observed an increased risk of CBC in women with increasing tumour size (p-trend < 0.05) and with ≥10 affected lymph nodes compared to node-negative cancer (adjusted HR 1.8, 95% CI 1.2-2.7). Lobular histology of the initial cancer also increased the risk of CBC (adjusted HR 1.3, 95% CI 1.1-1.6). Women with CBC had a worse prognosis than women with UBC, especially women with a short interval between the two cancers (adjusted HR 2.8, 95% CI 2.3-3.5 for CBC ≤5 years and HR 2.1, 95% CI 1.5-2.9 for CBC >5 years, compared to UBC). Increasing size of the contralateral tumour further increased the risk of dying from breast cancer (p-trend < 0.0001), as did affected lymph nodes (HR 4.6, 95% CI 3.4-6.2 vs. HR 2.1, 95% CI 1.6-2.6), high grade (p-trend < 0.001), lobular histology (HR 3.8, 95% CI 2.6-5.6 vs. HR 2.3, 95% CI 1.8-2.9 for ductal) and hormone receptor negativity (ER: HR 4.9, 95% CI 3.6-6.5 vs. HR 1.7, 95% CI 1.3-2.2; PR: HR 3.5, 95% CI 2.7-4.6 vs. HR 1.6, 95% CI 1.2-2.2). Conclusions: The influence of advanced stage of breast cancer on the risk of CBC together with a substantially poor prognosis for women in whom CBC occurred shortly after the initial cancer may imply that for some women CBC is a manifestation of active disease rather than a new primary. These findings indicate that surveillance and treatment plans may have to be adapted accordingly for women with a short interval between the initial and CBC.
183. Elucidation of Alpha-1 Antitrypsin Levels in Human Infant Blood Samples
Authors: Heather S. Loring, Alisha M. Gruntman, Qiushi Tang, Christian Mueller, Terence R. Flotte
Journal: Molecular Therapy (2016)

Alpha-1 antitrypsin (AAT) is a serum anti-protease that is produced in the liver and secreted into the circulation to function in the lung, protecting the alveolar interstitium from degradation by neutrophil elastase. AAT deficiency is a monogenic disease that results from mutations to the AAT gene. In the case of the PiZ mutation, the mutant Z-AAT produced in the liver undergoes loop-sheet polymerization inhibiting the secretion of AAT from the hepatocytes into the blood stream. Since AAT is sequestered in the liver, the protein is incapable of inhibiting neutrophil elastase's destruction of the alveolar epithelium, resulting in progressive lung disease. Accumulation of Z-AAT within the hepatocyte endoplasmic reticulum leads to hepatocellular stress, which can result in acute or chronic liver disease. About 5% of children afflicted with AAT deficiency develop acute liver failure within the first year of life. The cause for this acute liver failure in young patients has not yet been elucidated. Previous analysis of AAT levels in a mouse model expressing human Z-AAT from the endogenous AAT promoter has shown a considerable increase in hAAT concentration within the first few weeks of life, peaking at about 8.0*106 ng/mL at eight weeks, followed by a decrease in AAT concentration leveling out at 4.0*106 ng/mL at eighteen weeks of age. If the AAT promoter is regulated in a similar fashion in humans, one might predict that higher AAT expression in the early neonatal period may lead to increased accumulation of mutant AAT within the hepatocytes and precipitate fulminant liver disease early in life. In order to investigate this possibility, AAT levels were measured in healthy human infants over the course of the first two years of life. AAT levels were determined using a modified sandwich enzyme-linked immunosorbent assay (ELISA). Infant AAT levels demonstrate a biphasic trend with an initial increase to a maximum mean level of 2.8*106 ng/mL at five months, followed by a gradual decreasing trend. Mean levels remain higher than mean adult levels (1.3*106 ng/mL) up to twenty-four months of age and higher than previously reported infant levels (0.93*106 - 2.51*106 ng/mL) up to thirteen months of age.
Controlling the 3D architecture of Self-Lifting Auto-generated Tissue Equivalents (SLATEs) for optimized corneal graft composition and stability
Authors: Ricardo M. Gouveia, Elena González-Andrades, Juan C. Cardona, Carmen González-Gallardo, Ana M. Ionescu, Ingrid Garzon, Miguel Alaminos, Miguel González-Andrades, Che J. Connon
Journal: Biomaterials (2016)

Ideally, biomaterials designed to play specific physical and physiological roles in vivo should comprise components and microarchitectures analogous to those of the native tissues they intend to replace. For that, implantable biomaterials need to be carefully designed to have the correct structural and compositional properties, which consequently impart their bio-function. In this study, we showed that the control of such properties can be defined from the bottom-up, using smart surface templates to modulate the structure, composition, and bio-mechanics of human transplantable tissues. Using multi-functional peptide amphiphile-coated surfaces with different anisotropies, we were able to control the phenotype of corneal stromal cells and instruct them to fabricate self-lifting tissues that closely emulated the native stromal lamellae of the human cornea. The type and arrangement of the extracellular matrix comprising these corneal stromal Self-Lifting Analogous Tissue Equivalents (SLATEs) were then evaluated in detail, and was shown to correlate with tissue function. Specifically, SLATEs comprising aligned collagen fibrils were shown to be significantly thicker, denser, and more resistant to proteolytic degradation compared to SLATEs formed with randomly-oriented constituents. In addition, SLATEs were highly transparent while providing increased absorption to near-UV radiation. Importantly, corneal stromal SLATEs were capable of constituting tissues with a higher-order complexity, either by creating thicker tissues through stacking or by serving as substrate to support a fully-differentiated, stratified corneal epithelium. SLATEs were also deemed safe as implants in a rabbit corneal model, being capable of integrating with the surrounding host tissue without provoking inflammation, neo-vascularization, or any other signs of rejection after a 9-months follow-up. This work thus paves the way for the de novo bio-fabrication of easy-retrievable, scaffold-free human tissues with controlled structural, compositional, and functional properties to replace corneal, as well as other, tissues.
Abstract 2992: The landscape of long non-coding RNAs in cancer
Authors: Yashar S. Niknafs, Matthew K. Iyer, Arul M. Chinnaiyan
Journal: Cancer Research (2015)

Abstract Long non-coding RNAs (lncRNAs) are emerging as important players in cancer. The emergence of high-throughput RNA sequencing (RNA-Seq) technology provides a revolutionary means for systematic discovery of transcribed elements. However, efforts to catalog lncRNAs have thus far failed to appreciate the transcriptional robustness and complexity in the human genome because they were confined to select cell lines or small numbers of mostly normal tissue. In order to delineate genome-wide lncRNA expression, we curated 7,256 RNA-Seq libraries comprising over 43 terabases of sequence from 25 independent studies including tumors, normal tissues, and cell lines. The data were processed using ab initio transcriptome meta-assembly methodologies to develop a consensus of 91,013 expressed genes. Over 68% (58,648) of genes were classified as lncRNAs, of which 79% (48,952) were previously unannotated. About 1% (597) of the lncRNAs harbor ultraconserved elements and 7% (3,900) overlap disease-associated single nucleotide polymorphisms (SNPs). To prioritize lineage-specific, disease-associated lncRNA expression, we developed a non-parametric method for differential expression testing called Sample Set Enrichment Analysis (SSEA), and nominated 7,942 lineage- or cancer-associated lncRNA genes. In order to interrogate potential functionality for these lncRNAs, gene set enrichment testing was performed on genes correlated with each lncRNA. By uncovering this expansive landscape of cancer-associated lncRNAs, we provide the scientific community a powerful starting point to begin investigating their biological relevance. We anticipate that the lncRNAs identified by this study, as well as the computational tools developed herein, will provide a foundation for lncRNA genomics, biomarker development, and the delineation of cancer disease mechanisms. Citation Format: Yashar S. Niknafs, Matthew K. Iyer, Arul M. Chinnaiyan. The landscape of long non-coding RNAs in cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2992. doi:10.1158/1538-7445.AM2015-2992
Abstract 2050: Persistent STAT3 signaling contributes to the resistance of anti cancer drugs doxorubicin and cisplatin, and MEK inhibitor AZD6244 in human sarcoma cells
Authors: Xiaojuan Wu, Hui Xiao, Chenglong Li, Jiayuh Lin
Journal: Cancer Research (2015)

Abstract Signal Transducer and Activator of Transcription 3 (STAT3) signaling pathway is activated in response to cytokines and growth factors. Persistently activated STAT3 are frequently detected in many types of human cancers and are believed to play an important role in their oncogenesis. Stat3 has been classified as a proto-oncogene because activated STAT3 can mediate oncogenic transformation in cultured cells and tumor formation in nude mice. We previously demonstrated that persistently activated STAT3 is frequently detected in human sarcoma such as rhabdomyosarcoma. To further examine the role of persistent TAT3 signaling plays in rhabdomyosarcoma, we used genetic approaches to either knock-down the expression of STAT3 using short hairpin RNA (ShRNA) or expressed constitutive active STAT3 protein. Knock-down the expression of STAT3 in rhabdomyosarcoma cells that express persistent STAT3 signaling, reduced the cell viability and sensitized cells to anti-cancer drugs doxorubicin and cisplatin. On the other hand, expression of constitutive active STAT3 protein in rhabdomyosarcoma cell lines lacking persistent STAT3 signaling decreased the sensitivity of those cells to doxorubicin and cisplatin. Furthermore, a MEK inhibitor, AZD6244 that is being tested in human cancer clinical trials unexpectedly induced STAT3 phosphorylation suggesting inducing of STAT3 may induce intrinsic resistance to MEK inhibitor. Accordingly, knock down of STAT3 sensitize sarcoma cells to MEK inhibitor treatments. To further translate our finding to potential cancer therapy, we tested a small molecular STAT3-selective inhibitor LY5 in sarcoma cells expressing persistent STAT3 signaling. Our data demonstrated that LY5 inhibited STAT3 phosphorylation, STAT3 DNA binding activity, and the migration of sarcoma cells. In addition, the combination of LY5 with anti-cancer drugs doxorubicin and cisplatin and the MEK inhibitor, AZD6244 also shown stronger inhibitory effects than single agent alone. In summary, our results using both genetic and small molecule approaches demonstrated that persistent STAT3 signaling contributes to the resistance of anti-cancer drugs doxorubicin and cisplatin, and MEK inhibitor in human sarcoma cells. They also implicated a potential cancer therapy strategy with the combination of STAT3 inhibitor with doxorubicin, cisplatin, and MEK inhibitor in sarcoma cells expressing persistent STAT3 signaling. Citation Format: Xiaojuan Wu, Hui Xiao, Chenglong Li, Jiayuh Lin. Persistent STAT3 signaling contributes to the resistance of anti cancer drugs doxorubicin and cisplatin, and MEK inhibitor AZD6244 in human sarcoma cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2050. doi:10.1158/1538-7445.AM2015-2050
Early Treatment of Anemia of Lower Risk MDS by Erythropoiesis-Stimulating Agents (ESAs): A Report On 112 Cases.
Authors: Sophie Park, C. Kelaidi, Rosa Sapena, D. Vassilieff, Odile Beyne-Rauzy, Valerie Coiteux, Norbert Vey, Christophe Ravoet, Stéphane Cheze, Christian Rose, Laurence Legros, Aspasia Stamatoullas, Martine Escoffre-Barbe, Agnes Guerci, MP Chaury, Pierre Fenaux, Francois Dreyfus
Journal: Blood (2009)
Abstract 1495: Quantification of blood perfusion in rhabdomyosarcoma xenograft in 3D using contrast-enhanced ultrasound imaging
Authors: Abbas Shirinifard, Suresh Thiagarajan, András Sablauer
Journal: Cancer Research (2015)

Abstract This study aims to estimate individual 3D perfusion maps using nonlinear contrast-enhanced ultrasound imaging (CEUS) over the volume of individual rhabdomyosarcoma xenograft tumors in CD1 nude mice. We implanted the tumors subcutaneously close to the right kidney. We administered MicroMarker® microbubbles via tail vein catheter and acquired images using VisualSonics VEVO 2100 imaging system. We used the burst-replenishment technique to image tumor perfusion. To maintain a steady concentration of microbubbles, we used a programmable pump to inject a small bolus followed by constant infusion, achieving a steady state in less than 1 min, significantly shorter than the commonly used constant infusion without an initial bolus. Our preliminary analysis showed that the nonlinear CEUS signal intensities of kidney cortex have less than 20% variation between mice. We used a custom program to acquire the CEUS perfusion images over a 3D volume that included the tumor and the right kidney. We used the kidney as a reference organ to normalize whole tumor perfusion data. We applied temporal clustering methods to identify regions with similar perfusion profiles. We fitted three perfusion models to each region: a) mono-exponential, b) lognormal, c) beam-specific. We compared the performance of the models based on their overall quality of fit (across all the regions) and their error in estimated pre-burst signal level. Our preliminary analysis showed that log-normal and multi-vessel beam-specific models provide better performance than the mono-exponential model. We estimated individual 3D perfusion maps based on the model fits. These perfusion maps over the entire tumor volume represent tumor perfusion more accurately than the commonly used methods based on a single 2D plane over a region of interest and without including a reference organ. Our approach quantifies intratumoral blood perfusion heterogeneity and enables comparison of perfusion across individuals. Our method is extensible to other animal models and cancer types provided they can be imaged using ultrasound and a reference tissue can be imaged reliably in tandem on a subset of planes containing the tumor. Citation Format: Abbas Shirinifard, Suresh Thiagarajan, András Sablauer. Quantification of blood perfusion in rhabdomyosarcoma xenograft in 3D using contrast-enhanced ultrasound imaging. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1495. doi:10.1158/1538-7445.AM2015-1495
Patient access to breast reconstruction after mastectomy and long-term outcomes.
Authors: M. Morrow, A. K. Alderman, S. T. Hawley, S. J. Katz
Journal: Journal of Clinical Oncology (2011)

6021 Background: Little is known about factors associated with current rates of breast reconstruction after mastectomy or longer-term outcomes of different reconstructive options in diverse population-based samples. Methods: We surveyed 2245 women newly diagnosed with breast cancer and reported to the Detroit and Los Angeles SEER registries from 6/05-2/07 and merged these data to SEER. Patients were surveyed again about 4 years after diagnosis (expected n=1520). We report on a preliminary sample of 707 patients. Results: 249 patients (35.2%) had mastectomy as initial therapy. Of those, 110 (44%) received reconstruction (62% immediate, 38% delayed). One-third had autologous tissue and two-thirds had an implant (equally divided between saline and silicone) reconstruction. Less than one-quarter (22.8%) of women who received reconstruction were dissatisfied with the cosmetic results, and 28% felt the outcome did not match expectations. Women who received reconstruction were slightly more satisfied with their breast and body appearance than those who received mastectomy alone, but less satisfied than those who received BCS (5 pt scale score 3.2, 3.0, 3.5 for reconstruction, mastectomy alone, and BCS, respectively, p<.001, controlling for age). Most common reasons for not getting reconstruction were related to patient attitudes about the surgery: Half (52%) reported that they did not want more surgery or that reconstruction was not important and one-third (34%) were concerned about possible complications. Barriers to care were less commonly endorsed: 18% reported that insurance would not cover reconstruction or that they could not find a surgeon who accepted insurance (12%). 37% of those who did not get reconstruction were dissatisfied with the information they received about it. About 15% of women were still considering reconstruction at time of re-survey. Conclusions: While some women were dissatisfied with the results of breast reconstruction, overall, satisfaction with body appearance was slightly higher than for women with mastectomy alone. The majority of women who did not get reconstruction did not want it and few women continue to consider it. However, some financial and informational barriers may persist.
The Ratio of Angiopoietin-1 to Angiopoietin-2 Is Reduced and Predicts Independently for Survival in Newly Diagnosed Patients with Multiple Myeloma.
Authors: Meletios A. Dimopoulos, Konstantinos Anargyrou, Eirini Katodritou, Efstathios Kastritis, Anastasia Pouli, Evridiki Michali, Evgenia Verrou, Anastasia Banti, Konstantinos Tsionos, Aikaterini Stefanoudaki, Konstantinos Zervas, Evangelos Terpos
Journal: Blood (2007)
Clinical relevance of dimensional bone and soft tissue alterations post‐extraction in esthetic sites
Authors: Vivianne Chappuis, Mauricio G. Araújo, Daniel Buser
Journal: Periodontology 2000 (2016)

Abstract The key to achieving pleasing esthetics in implant dentistry is a thorough understanding of the biological processes driving dimensional bone and soft tissue alterations post‐extraction. The aim of the present report is first to characterize the extent of bone and soft tissue changes post‐extraction and second to identify potential factors influencing tissue preservation in order to facilitate successful treatment outcomes. The facial bone wall thickness has been identified as the most critical factor influencing bone resorption and can be used as a prognostic tool in order to identify sites at risk for future facial bone loss subsequent to tooth extraction. Clinical studies indicated that thin bone wall phenotypes exhibiting a facial bone wall thickness of 1 mm or less revealed progressive bone resorption with a vertical loss of 7.5 mm, whereas thick bone wall phenotypes showed only minor bone resorption with a vertical loss of 1.1 mm. This is in contrast to the dimensional soft tissue alterations. Thin bone wall phenotypes revealed a spontaneous soft tissue thickening after flapless extraction by a factor of seven, whereas thick bone wall phenotypes showed no significant changes in the soft tissue dimensions after 8 weeks of healing. In sites exhibiting a limited bone resorption rate, immediate implant placement may be considered. If such ideal conditions are not present, other timing protocols are recommended to achieve predictable and pleasing esthetics. Socket preservation techniques for ridge preservation utilizing different biomaterials and/or barrier membranes often result in a better maintenance of tissue volumes, although the inevitable biological process of post‐extraction bone resorption and bone modeling cannot be arrested. In summary, the knowledge of the biological events driving dimensional tissue alterations post‐extraction should be integrated into the comprehensive treatment plan in order to limit tissue loss and to maximize esthetic outcomes.