Compartment model predicts VEGF secretion and investigates the effects of VEGF Trap in tumor-bearing mice
Angiogenesis, the formation of new blood vessels from existing vasculature, is important in tumor growth and metastasis. A key regulator of angiogenesis is vascular endothelial growth factor (VEGF), which has been targeted in numerous anti-angiogenic therapies aimed at inhibiting tumor angiogenesis. Systems biology approaches, including computational modeling, are useful for understanding this complex biological process and can aid in the development of novel and effective therapeutics that target the VEGF family of proteins and receptors. We have developed a computational model of VEGF transport and kinetics in the tumor-bearing mouse, which includes three-compartments: normal tissue, blood, and tumor. The model simulates human tumor xenografts and includes human (VEGF121 and VEGF165) and mouse (VEGF120 and VEGF164) isoforms. The model incorporates molecular interactions between these VEGF isoforms and receptors (VEGFR1 and VEGFR2), as well as co-receptors (NRP1 and NRP2). We also include important soluble factors: soluble VEGFR1 (sFlt-1) and α-2-macroglobulin. The model accounts for transport via macromolecular transendothelial permeability, lymphatic flow, and plasma clearance. We have fit the model to available in vivo experimental data on the plasma concentration of free VEGF Trap and VEGF Trap bound to mouse and human VEGF in order to estimate the rates at which parenchymal cells (myocytes and tumor cells) and endothelial cells secrete VEGF. Interestingly, the predicted tumor VEGF secretion rates are significantly lower (0.007-0.023 molecules/cell/s, depending on the tumor microenvironment) than most reported in vitro measurements (0.03-2.65 molecules/cell/s). The optimized model is used to investigate the interstitial and plasma VEGF concentrations and the effect of the VEGF-neutralizing agent, VEGF Trap (aflibercept). This work complements experimental studies performed in mice and provides a framework with which to examine the effects of anti-VEGF agents, aiding in the optimization of such anti-angiogenic therapeutics as well as analysis of clinical data. The model predictions also have implications for biomarker discovery with anti-angiogenic therapies.
Tumor Infiltrating Lymphocytes (TILs) as a Function of Histological Subtype and Genetic Background of Ovarian Epithelial Carcinomas
Not available at this time.
Gene Sequencing for Pathogenic Variants Among Adults With Breast and Ovarian Cancer in the Caribbean
Importance Rates of breast and ovarian cancer are high in the Caribbean; however, to date, few published data quantify the prevalence of inherited cancer in the Caribbean population.
Objective To determine whether deleterious variants in genes that characterize the hereditary breast and ovarian cancer syndrome are associated with the development of breast and ovarian cancer in the English- and Creole-speaking Caribbean populations.
Design, Setting, and Participants This multisite genetic association study used data from germline genetic test results between June 2010 and June 2018 in the Bahamas, Cayman Islands, Barbados, Dominica, Jamaica, Haiti, and Trinidad and Tobago. Next-generation sequencing on a panel of 30 genes and multiplex ligation-dependent probe amplification (BRCA1 and BRCA2) were performed. Medical records were reviewed at time of study enrollment. Women and men diagnosed with breast and ovarian cancer with at least 1 grandparent born in the participating study sites were included; 1018 individuals were eligible and consented to participate in this study. Data were analyzed from November 4, 2019, to May 6, 2020.
Exposures Breast and/or ovarian cancer diagnosis
Main Outcomes and Measures Rate of inherited breast and ovarian cancer syndrome and spectrum and types of variants.
Results Of 1018 participants, 999 (98.1%) had breast cancer (mean [SD] age, 46.6 [10.8] years) and 21 (2.1%) had ovarian cancer (mean [SD] age, 47.6 [13.5] years). Three individuals declined to have their results reported. A total of 144 of 1015 (14.2%) had a pathogenic or likely pathogenic (P/LP) variant in a hereditary breast and ovarian cancer syndrome gene. A total of 64% of variant carriers had P/LP variant in BRCA1, 23% in BRCA2, 9% in PALB2 and 4% in RAD51C, CHEK2, ATM, STK11 and NBN. The mean (SD) age of variant carriers was 40.7 (9.2) compared with 47.5 (10.7) years in noncarriers. Individuals in the Bahamas had the highest proportion of hereditary breast and ovarian cancer (23%), followed by Barbados (17.9%), Trinidad (12%), Dominica (8.8%), Haiti (6.7%), Cayman Islands (6.3%), and Jamaica (4.9%). In Caribbean-born women and men with breast cancer, having a first- or second-degree family member with breast cancer was associated with having any BRCA1 or BRCA2 germline variant (odds ratio, 1.58; 95% CI, 1.24-2.01; P < .001). A BRCA1 vs BRCA2 variant was more strongly associated with triple negative breast cancer (odds ratio, 6.33; 95% CI, 2.05-19.54; P = .001).
Conclusions and Relevance In this study, among Caribbean-born individuals with breast and ovarian cancer, 1 in 7 had hereditary breast and ovarian cancer. The proportion of hereditary breast and ovarian cancer varied by island and ranged from 23% in the Bahamas to 4.9% in Jamaica. Each island had a distinctive set of variants.
The Activist Life of E.J. Josey: Josey Scholar Discusses the Trailblazer’s Impact on The Library World
Renate L. Chancellor, associate professor in the Department of Library and Information Science at Catholic University of America in Washington, D.C., and author of E. J. Josey: Transformational Leader of the Modern Library Profession (Rowman and Littlefield, 2020), is a leading Josey scholar. American Libraries spoke with her about his life, activism, and impact on the library world.
Ask Dr. Chu: An Interview with a Peruvian-born Chinese Canadian Living in the U.S.
The following interview with Information Studies professor Clara Chu explores some of the central issues facing immigrant library users. She shares with us some of her life experiences as an immigrant and her views on the current immigration debate as well as its implications for information professionals and library educators.
Law libraries and the formation of the legal profession in the late Middle Ages
Historians typically engage in research that attempts to recount “past events pertaining to the establishment, maintenance, and utilization of systematically arranged collections of recorded information or knowledge.”1 Nowhere could this be more aptly demonstrated than in Stanley Chodorow’s study on the emergence of law libraries in the Middle Ages. This work was originally presented on February 15, 2006, at the second annual Tarleton Law Library Rare Book Lecture at the University of Texas School of Law and subsequently published as a book for those who missed the lecture or wanted a transcript.
The Desegregation of Public Libraries in the Jim Crow South: Civil Rights and Local Activism
We know the stories, or at least we think that we do—the Greensboro sit-ins, the bombing in Birmingham, the Freedom Riders, and the “I Have a Dream” speech. We have seen the images of protests and violence. We know the all-too-familiar casualties of the civil-rights movement—Martin Luther King, Jr., John F. Kennedy, Malcolm X, Andrew Goodman, Michael Schwerner, and James Chaney. Yet, countless unsung heroines and heroes put their lives on the line for desegregation in venues other than lunch counters, public schools, and universities. Wayne and Shirley Wiegand’s study of the integration of public libraries in the Jim Crow south is a worthy contribution to a little-explored body of work related to American library history.
Educating librarians in the contemporary university: An essay on iSchools and emancipatory resilience in library and information science
Copyright in the Information Age
For centuries, librarians and other information professionals such as those who work in museums, archives, and other information centers have grappled with the legal and ethical considerations that affect the creation, organization, dissemination and use of information. Libraries and information centers typically house collections of copyrighted materials that may potentially pose legal consequences for libraries and library users. Whether the issue is monitoring the amount of photocopies made in a public library or the potential copyright infringement of providing articles for course reserves in a university library; librarians find themselves in the position of balancing the needs of the user with the rights of the creator. With the information explosion of the 21st century, copyright law presents even greater challenges for information professionals. The Internet and the digital revolution have changed the interpretation of copyright law in order to provide the greatest protection for creators’ works. This chapter offers a discussion on copyright in this ever-changing age of information.
Race as Multidimensional: The Personal Shaping the Professional in the Library and Information Field
As individuals, each contributor speaks in their own voice, and as a collective, the authors move the race dialogue forward by speaking about dimensions of race from their own experiences, representing individual stories, and allowing their intersections to be revealed.