bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract B29: Dissecting the effects of Brd4 short isoform on breast cancer progression
Authors: Zhu Xinyi , Hunter Kent W. 
Published: May 2019

Abstract
Breast cancer is one of the most common female malignancies in the United States with metastatic disease being the main contributor to breast cancer morbidity and mortality. Our lab previously identified BRD4, a member of the bromodomain family, as a regulator of breast cancer progression. Brd4 is a chromatin-modifying factor that regulates the expression of a large set of genes. Brd4 is normally expressed as two isoforms. The long isoform (Brd4-LF) contains two bromodomains in the N-terminus, an ET domain, a serine-rich SEED domain, and a proline-rich C-terminus. The short isoform (Brd4-SF) differs from the long isoform by a deletion of the proline-rich C-terminus and a three amino acid difference on the N-terminal domain. Previous studies in our laboratory indicate that these two isoforms have opposing effects on breast cancer progression. Highly metastatic mouse mammary tumor cells overexpressing Brd4-LF suppressed tumor growth and dissemination, whereas overexpression of Brd4-SF increased metastatic outgrowth in lungs. We have shown that these two isoforms are found in different compartments within the cell nucleus, leading to altered interaction with nuclear proteins. Brd4-LF is localized in the nuclear matrix while Brd4-SF is found in the nuclear envelope where it interacted with the LINC complex and known metastasis susceptibility proteins RRP1B and SIPA1. Given that these two isoforms reside in different subnuclear locations, we hypothesize that the isoforms bind to different sets of genes. To test this hypothesis we are utilizing the chromatin-immunoprecipitation sequencing (ChIP-seq) assay to characterize the genetic interactions associated with Brd4-SF. Identification of the Brd4-SF interacting genes will provide us with mechanistic insight into the underlying causes of the different metastatic outcomes promoted by the two isoforms, highlighting potential targets for future targeted therapies.
Citation Format: Xinyi Zhu, Kent W. Hunter. Dissecting the effects of Brd4 short isoform on breast cancer progression. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Metastasis; 2015 Nov 30-Dec 3; Austin, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(7 Suppl):Abstract nr B29.
Abstract B40: Lineage selective extracellular matrix interactions required for metastatic lung cancer
Authors: Nguyen Don X. 
Published: May 2019

Abstract
Background: Lung cancers are biological heterogeneous malignancies with poor prognosis. The underlying mechanisms of this heterogeneity and their biological consequences for metastasis are poorly understood. We previously examined the molecular relationship between epithelial differentiation states, airway regeneration, lung cancer subtypes, and clinical outcome. By integrating genomics, bioinformatic, and experimental models of lung cancer metastasis, we identified a subset of metastatic lung adenocarcinoma (LUAD) defined by its expression of a novel cell lineage gene expression program (Cheung et al., Cancer Cell 2013).
Results: Here we further define the molecular characteristics of this aggressive LUAD subgroup and find that it is driven by epigenetic silencing of know tumor suppressive non-coding RNAs, including mir-34a-c. This in turn activates genes encoding for specific extracellular matrix (ECM) interacting proteins. These ECM proteins include proteoglycans abundant in the inflammatory stroma of human lung cancers and lung tissue from patients with pulmonary fibrosis. Over-expressions of these proteoglycans and their corresponding cell surface receptors are defining features of recognized LUAD histotypes. In an experimental mouse model, genetic perturbations of these ECM/cell surface interactions inhibits the metastasis re-initiating capacity of LUAD cells to distant organs such as the brain. Significantly, these ECM-tumor cell interactions may also be disrupted using targeted agents currently in clinical trials.
Conclusions: Our data provide a mechanistic link between the effectors of airway homeostasis, pulmonary fibrosis, and metastasis initiation by specific lung cancers. Consequently, we provide rational strategies to re-position current therapies to target the tumor microenvironment of metastatic lung adenocarcinomas.
Citation Format: Don X. Nguyen. Lineage selective extracellular matrix interactions required for metastatic lung cancer. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Metastasis; 2015 Nov 30-Dec 3; Austin, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(7 Suppl):Abstract nr B40.
Abstract B44: Keratin-associated protein 5-5 controls cytoskeletal function and cancer cell vascular invasion
Authors: Berens Eric B. , Sharif Ghada M. , Schmidt Marcel O. , Shuptrine Casey W. , Weiner Louis M. , Glasgow Eric , Riegel Anna T. , Wellstein Anton 
Published: May 2019

Abstract
Cancer cell vascular invasion is a crucial step in the malignant progression towards metastasis. Here we used a genome-wide RNAi screen with E0771 mammary cancer cells to uncover drivers of endothelial monolayer invasion. We identified keratin-associated protein 5-5 (Krtap5-5) as a candidate. Krtap5-5 belongs to large family of cysteine-rich proteins that is implicated in crosslinking keratin intermediate filaments during hair formation. To date, no role of these proteins in cancer has been reported. We found that depletion of Krtap5-5 from cancer cells led to cell blebbing, a loss of keratins 14 and 18 in addition to the upregulation of vimentin intermediate filaments. Krtap5-5 depletion did not impact cell viability but reduced cell motility and extravasation of cancer cells into tissues in a zebrafish model of extravasation. We conclude that Krtap5-5 is a previously unknown regulator of cytoskeletal function in cancer cells that modulates cell motility and vascular invasion.
Citation Format: Eric B. Berens, Ghada M. Sharif, Marcel O. Schmidt, Casey W. Shuptrine, Louis M. Weiner, Eric Glasgow, Anna T. Riegel, Anton Wellstein. Keratin-associated protein 5-5 controls cytoskeletal function and cancer cell vascular invasion. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Metastasis; 2015 Nov 30-Dec 3; Austin, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(7 Suppl):Abstract nr B44.
Abstract B45: An early treatment window to target FAK-dependent collective invasion in Lkb1-mutant lung adenocarcinoma
Authors: Gilbert-Ross Melissa , Konen Jessica , Shupe John , Koo Junghui , Sica Gabriel L. , Ramalingam Suresh S. , Fu Haian , Khuri Fadlo R. , Zhou Wei , Marcus Adam I. 
Published: May 2019

Abstract
LKB1 is the 2rd most commonly mutated tumor suppressor gene in human lung adenocarcinoma, and a biomarker of aggressive disease in stage IV KRAS mutant lung cancer patients. We have previously published that LKB1 acts to limit focal adhesion kinase (FAK) activity in human lung cancer cells to restrict cell adhesion and migration. Based on our prior published data we hypothesize that FAK inhibition will suppress invasion and metastasis in LKB1-mutant tumors in vivo , and represent a viable clinical strategy to target this high-risk patient population. To investigate our hypothesis, we have developed a novel lentiviral-Cre KrasG12D; Lkb1fl/fl Rosa-luciferase genetically engineered mouse model (GEMM) (KLLLenti) that develops 100% adenocarcinomas, and produces a bioluminescent output that correlates with tumor burden, tumor grade, and degree of metastatic colonization of the lymph node. We show that stage IV KLLLenti primary tumors have elevated levels of active FAK in a subset of invasive cells that maintain collective contact via E-Cadherin. Importantly, treatment of KLLLenti mice with a pharmacologic FAK inhibitor potently suppresses invasive progression of primary tumors. Moreover, KLLLenti tumors treated at later stages progress to the same degree as vehicle-treated mice. This result suggests a ‘therapeutic window’ of opportunity, and argues that FAK inhibitors should be part of first-line therapy to treat LKB1-mutant lung cancer patients. We further pursue mechanistic studies to investigate how Lkb1-mutant tumor tissue gains a metastastic advantage in vivo, and using a combination of 3D tumor spheroid assays and multiphoton microscopy present results that Lkb1-mutant tumors use a unique form of hybrid or transitional invasion that on depends on both FAK-based adhesion and collective migration and in doing so, are equipped to more efficiently invade into the collagen-dense microenvironment of the lung. Our studies suggest that when used early, FAK inhibitors may be a viable clinical strategy to prevent metastasis in the LKB1-mutant patient population, and begin to define alternate escape pathways by which this highly invasive cell population may escape first-line therapy.
Citation Format: Melissa Gilbert-Ross, Jessica Konen, John Shupe, Junghui Koo, Gabriel L. Sica, Suresh S. Ramalingam, Haian Fu, Fadlo R. Khuri, Wei Zhou, Adam I. Marcus. An early treatment window to target FAK-dependent collective invasion in Lkb1-mutant lung adenocarcinoma. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Metastasis; 2015 Nov 30-Dec 3; Austin, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(7 Suppl):Abstract nr B45.
Abstract B67: Matriptase is involved in COX-2 signaling-induced prostate cancer cell invasion
Authors: Ko Chun-Jung , Lu Ying-Chieh , Lai Pee-Fang , Hsiao Pei-Wen , Lee Ming-Shyue 
Published: May 2019

Abstract
Chronic inflammation plays an important role in the early development and progression of cancer. Cyclooxygenases-2 (COX-2) is a key rate-limiting enzyme which regulates of inflammation-producing prostaglandins. Several studies have shown that COX-2 is found with overexpression in human cancers (colon, breast, lung, prostate cancers, etc), and implicated in cancer cell invasion. Moreover, high COX-2 expression has been correlated with prostate cancer metastasis. However, the molecular mechanism that COX-2 promotes prostate cancer cell invasion is still unclear. In this study, we established a PC-3 cell invasion progression model (parental and M2I2 PC-3 cells) and found out that several inflammation-associated proteins, COX-2, p-JNK and IL-1β were up-regulated in M2I2 PC-3 cells. Therefore, we purposed that if COX-2 signaling plays a role in prostate cancer cell invasion and the involvement of matriptase in COX-2 signaling-induced cancer cell invasion. The results showed that COX-2 inhibitors (celebrex and sulindac sulfide) could suppress prostate cancer PC3 cell invasion and inhibited matriptase expression and activation. A COX-2 product PGE2 could induce matriptase activation and prostate cancer cell invasion. COX-2 overexpression also could up-regulate matriptase and enhance the cancer cell invasion, while COX-2 silencing antagonized both matriptase activation and cell invasion. Thus, our results indicate that COX-2 signaling can promote prostate cancer cell invasion, at least in part via up-regulating matriptase.
Citation Format: Chun-Jung Ko, Ying-Chieh Lu, Pee-Fang Lai, Pei-Wen Hsiao, Ming-Shyue Lee. Matriptase is involved in COX-2 signaling-induced prostate cancer cell invasion. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Metastasis; 2015 Nov 30-Dec 3; Austin, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(7 Suppl):Abstract nr B67.
Abstract IA12: Microfluidic isolation of circulating tumor cells and microvesicles from cancer patients
Authors: Stott Shannon L. 
Published: May 2019

Abstract
Malignant tumors will aggressively invade surrounding tissue due to rapidly dividing cancer cells that are nourished by an ample blood supply. As these cancer cells are multiplying, they release thousands of tiny particles into the blood stream, referred to as exosomes and microvesicles, which contain genetic information about the tumor. Whole cancer cells are also released from the tumor and these rare circulating tumor cells (CTCs) provide genetic and functional information about the patient's cancer. Through a collaborative effort between bioengineers, biologists, and clinicians, our group at MGH has developed microfluidic devices to isolate both of these rare circulating biomarkers from whole blood. Data from these devices will be presented with a focus on our recent effort to characterize microvesicles and CTCs from patients with glioblastoma. Through the microfluidic isolation of blood based biomarkers from glioblastoma patients, our goal is to obtain complementary data to the current standard of care radiologic measurements to help better guide treatment for this deadly cancer.
Citation Format: Shannon L. Stott. Microfluidic isolation of circulating tumor cells and microvesicles from cancer patients. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Metastasis; 2015 Nov 30-Dec 3; Austin, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(7 Suppl):Abstract nr IA12.
Abstract IA17: Collective epithelial routes to metastatic spread
Authors: Ewald Andrew J. 
Published: May 2019

Abstract
The spread of cancer to distant organs is the major driver of mortality in cancer and, unfortunately, few therapies are effective in patients with extensive metastatic disease. Our hypothesis is that deeper mechanistic insight into the biological basis of metastasis will lead to novel therapeutic concepts. We have focused our laboratory investigations on understanding how epithelial cells acquire the ability to release their connections with their neighbors, migrate through the stroma, and enter the systemic circulation. The prevailing model when we began was the epithelial to mesenchymal transition (EMT), which posited a loss of epithelial features in the cancer cells during metastasis. The EMT model was controversial, in part because metastatic tumors typically retain many epithelial features. However, it remained possible that epithelial features were lost during stages of transit that are difficult to impossible to observe in vivo.
To distinguish these possibilities, we developed novel 3D organoid assays to model normal epithelial growth, to determine the molecular requirements for Twist1 induced dissemination and to identify molecular programs driving the colonization of distant organs. The conclusions drawn across these studies are (1) that there are normal epithelial migratory programs that can be rapidly co-opted through activation of RTK signaling, (2) that the epithelial cell adhesion machinery can facilitate dissemination, and (3) that clusters of breast cancer cells utilize epithelial-specific gene expression (e.g. keratin-14) as they invade, disseminate, and colonize distant organs. These insights lead us to view metastasis as a process that can be accomplished without loss of epithelial character and that these epithelial routes to metastasis may have unique vulnerabilities compared to EMT models. We will discuss the latest progress in these studies and also technical advances in 3D culture that will accelerate metastasis research across organ sites.
Citation Format: Andrew J. Ewald. Collective epithelial routes to metastatic spread. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Metastasis; 2015 Nov 30-Dec 3; Austin, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(7 Suppl):Abstract nr IA17.
A contradição que não se comunica (The contradiction that cannot be told)
Authors: Godinho Ana 
Published: May 2019

Information and knowledge have never been produced so rapidly. Production that finally does not communicate, nor does it act, nor does it have the positive effects that are desired of transference to society. Hyperactivities, fascism, various pathologies, and contradictions, went into such an enterprise. And along with the most daring technological and scientific advances, an unmentionable barbarity is advancing in an overwhelming way. The planetary dangers that result from this production that is not communicated and which we often only become aware of do not cease to threaten us every day and insistently knock on the door. An ambiguous and dangerous global context makes us recover a hypothesis that is more than fifty years old. Proposed by Bateson with a very wide reach the concept of "double bind" helps us to think the relationship between education knowledge and politics.ResumoNunca se produziu tanto e tão aceleradamente informação e conhecimento. Produção que finalmente não se comunica, nem age, nem tem os efeitos positivos que se desejam de transferência para a sociedade. Hiperatividades, fascismos, patologias variadas, contradições e impasses entravam tamanho empreendimento. E a par dos avanços tecnológicos e científicos mais ousados uma barbárie inominável avança de forma avassaladora. Os perigos planetários que resultam desta produção que não se comunica e de que só amiúde nos tornamos conscientes não deixam de nos ameaçar todos os dias e bater com insistência à porta. Um contexto global tão ambíguo e perigoso faz-nos recuperar uma hipótese com mais de cinquenta anos. Proposta por Bateson com um alcance bastante vasto, o conceito de duplo impasse ou “double bind” ajuda-nos a pensar a relação entre educação, conhecimento e política.Keywords: Communication, Contradiction, Double bind, Populism.Palavras-chave: Comunicação, Contradição, Duplo impasse, Populismo.ReferencesBATESON, G. Vers une écologie de l’esprit. (Vol. 1 e 2), Paris: Seuil, 1980.BATESON, G.; RUESCH, J. Communication et société. Paris: Seuil, 1988.DELEUZE, G.; GUATTARI, F. L’Anti-Œdipe. Paris: Minuit, 1972.DELEUZE, G.; GUATTARI, F. Mille plateaux. Paris: Minuit, 1980.DELEUZE, G.; GUATTARI, F. O que é a Filosofia?. Lisboa: Presença, 1992.DELEUZE, G. Crítica e clínica. Lisboa: Ed. Século XXI, 2000.WATZLAWICK, P.; BEAVIN, J. H.; JACKSON, D. D. Pragmatics of human communication. A study of interactional patterns, pathologies and paradoxes. New York: W.W. Norton & Co, 1967.WATZLAWICK, P.; WEAKLAND, J.; FISCH, R. Changements: paradoxes et psychothérapie. Paris: Seuil,1975.
Assessment of Exit Temperature Pattern Factors in an Annular Gas Turbine Combustor: An Overview
Authors: Muduli S. K. , Mishra R. K. , Mishra P. C. 
Published: May 2019

Abstract
The present paper overviews the works carried out on achieving desired temperature pattern factors at combustor exit in gas turbine engines. These pattern factors are very important from the point of engine performance and life of turbine blades and vanes. They are controlled by a number of geometrical parameters such as liner front-end air passages, primary air holes, atomizer characteristics and air swirl number and dilution zone geometrical configuration. Combustor inlet pressure, Mach number, velocity profile and fuel-air ratio are the major operating parameters that influence the pattern factors. Due to the design uniqueness and importance of pattern factors, it is always a challenge to assess the pattern factors over a wide range of mission points for a gas turbine combustor designed for combat aircraft.
Low-Dielectric-Constant Materials for ULSI Interlayer-Dielectric Applications
Authors: Lee Wei William , Ho Paul S. 
Published: May 2019

Continuing improvement of microprocessor performance historically involves a decrease in the device size. This allows greater device speed, an increase in device packing density, and an increase in the number of functions that can reside on a single chip. However higher packing density requires a much larger increase in the number of interconnects. This has led to an increase in the number of wiring levels and a reduction in the wiring pitch (sum of the metal line width and the spacing between the metal lines) to increase the wiring density. The problem with this approach is that—as device dimensions shrink to less than 0.25 μm (transistor gate length)—propagation delay, crosstalk noise, and power dissipation due to resistance-capacitance (RC) coupling become significant due to increased wiring capacitance, especially interline capacitance between the metal lines on the same metal level. The smaller line dimensions increase the resistivity (R) of the metal lines, and the narrower interline spacing increases the capacitance (C) between the lines. Thus although the speed of the device will increase as the feature size decreases, the interconnect delay becomes the major fraction of the total delay and limits improvement in device performance.To address these problems, new materials for use as metal lines and interlayer dielectrics (ILD) as well as alternative architectures have been proposed to replace the current Al(Cu) and SiO2 interconnect technology.
Nanoporous Silica as an Ultralow-k Dielectric
Authors: Jin Changming , Luttmer J.D. , Smith Douglas M. , Ramos Teresa A. 
Published: May 2019

As feature sizes in integrated circuits approach 0.18 μm, problems with interconnect resistance-capacitance (RC) delay, power consumption, and crosstalk become more urgent. Integration of low-dielectric-constant (k) materials will partially mitigate these problems, but each candidate with k significantly lower than that of dense silica (k ∼ 4) suffers disadvantages. Current low-k commercialization emphasizes spin-on glasses (SOGs) and fluorinated SiO2 with k > 3, and a number of polymers are under development with k in the range of 2–3. These suffer from potential problems including thermal stability, mechanical properties, low thermal conductivity, and reliability. For some low-k materials, a protective liner covering the conductor is necessary. Although the material k is often cited, the value of practical concern is the effective k, which may be quite different because of this protective liner. As feature sizes shrink, the presence of the liner becomes more problematic and necessitates even lower k materials.Another approach employs nanoporous silica with k of ∼1–4. Porous silica has been classified as an aerogel (dried supercritically) or as a xerogel (dried by solvent evaporation). We use the term nanoporous silica since it captures the key material properties that may be independent of how the films are processed. The ultralow dielectric constant results from porosity incorporation. For a porous material, the dielectric constant is a combination of that of air (∼1) and of the solid phase. The variation of k with porosity (volume fraction of pores) appears in Figure 1.