1,721,027 research outputs found
Patient Derived Xenografts for Genome-Driven Therapy of Osteosarcoma
Full text linkAbstract: Osteosarcoma (OS) is a rare malignant primary tumor of mesenchymal origin affecting
bone. It is characterized by a complex genotype, mainly due to the high frequency of chromothripsis, which leads to multiple somatic copy number alterations and structural rearrangements. Any
effort to design genome-driven therapies must therefore consider such high inter- and intra-tumor
heterogeneity. Therefore, many laboratories and international networks are developing and sharing
OS patient-derived xenografts (OS PDX) to broaden the availability of models that reproduce OS
complex clinical heterogeneity. OS PDXs, and new cell lines derived from PDXs, faithfully preserve
tumor heterogeneity, genetic, and epigenetic features and are thus valuable tools for predicting drug
responses. Here, we review recent achievements concerning OS PDXs, summarizing the methods
used to obtain ectopic and orthotopic xenografts and to fully characterize these models. The availability of OS PDXs across the many international PDX platforms and their possible use in PDX clinical trials are also described. We recommend the coupling of next-generation sequencing (NGS) data
analysis with functional studies in OS PDXs, as well as the setup of OS PDX clinical trials and coclinical trials, to enhance the predictive power of experimental evidence and to accelerate the clinical
translation of effective genome-guided therapies for this aggressive disease
Cancer immunoprevention: from mice to early clinical trials
Full text linkAbstract Cancer immunoprevention is based on the fact that a functioning immune system controls tumor onset and development in humans and animals, thus leading to the idea that the enhancement of immune responses in healthy individuals could effectively reduce cancer risk later in life. Successful primary immunoprevention of tumors caused by hepatitis B and papilloma viruses is already implemented at the population level with specific vaccines. The immunoprevention of human tumors unrelated to infectious agents is an outstanding challenge. Proof-of-principle preclinical studies in genetically-modified or in carcinogen-exposed mice clearly demonstrated that vaccines and other immunological treatments induce host immune responses that effectively control tumor onset and progression, eventually resulting in cancer prevention. While a straightforward translation to healthy humans is currently unfeasible, a number of pioneering clinical trials showed that cancer immunoprevention can be effectively implemented in human cohorts affected by specific cancer risks, such as preneoplastic/early neoplastic lesions. Future developments will see the implementation of cancer immunoprevention in a wider range of conditions at risk of tumor development, such as the exposure to known carcinogens and genetic predispositions
Bioprofiling TS/A Murine Mammary Cancer for a Functional Precision Experimental Model
Full text linkThe TS/A cell line was established in 1983 from a spontaneous mammary tumor arisen in an inbred BALB/c female mouse. Its features (heterogeneity, low immunogenicity and metastatic ability) rendered the TS/A cell line suitable as a preclinical model for studies on tumor-host interactions and for gene therapy approaches. The integrated biological profile of TS/A resulting from the review of the literature could be a path towards the description of a precision experimental model of mammary cancer
Evaluation of metastatic burden and recovery of human metastatic cells from a mouse model
No full textMetastatic dissemination is the major cause
of death in cancer. Xenotransplantation of
tumor tissue into immunodeficient mice is a
widespread preclinical technique to study tumor
development. However, preclinical studies on the
spreading of metastases were so far hampered
by the poor dissemination of malignant human
tumors in conventional immunodeficient hosts,
like the nude mouse. The development of highly
immunodeficient knockout mice spurred a
new wave of metastatic model systems. It was
recently shown that human HER-2-positive
breast cancer cells, which do not metastasize
in nude mice, when implanted in knockout
mice with severe immunodeficiency, give rise
to multiorgan metastatic patterns resembling
those observed in human patients. The growth
of metastatic nodules in a variety of locations,
including brain, lungs, liver, kidneys, adrenals,
ovaries, and bone marrow, opens up the problem
of quantifying metastatic burden and recovering
human metastatic cells from mouse organs
for cellular and molecular studies in vitro .Here we used the Mouse Cell Depletion Kit
(Miltenyi Biotec) to enrich and quantify
metastatic human cells, derived from human
breast carcinoma, in a model of brain
metastases1 in NOD scid gamma (NOD.Cg-
Prkdc scid Il2rg tm1Wjl/SzJ, NSG) mice
HER Tyrosine Kinase Family and Rhabdomyosarcoma: Role in Onset and Targeted Therapy
Full text linkRhabdomyosarcomas (RMS) are tumors of the skeletal muscle lineage. Two main features
allow for distinction between subtypes: morphology and presence/absence of a translocation between
the PAX3 (or PAX7) and FOXO1 genes. The two main subtypes are fusion-positive alveolar
RMS (ARMS) and fusion-negative embryonal RMS (ERMS). This review will focus on the role of
receptor tyrosine kinases of the human epidermal growth factor receptor (EGFR) family that is
comprised EGFR itself, HER2, HER3 and HER4 in RMS onset and the potential therapeutic targeting
of receptor tyrosine kinases. EGFR is highly expressed by ERMS tumors and cell lines, in some cases
contributing to tumor growth. If not mutated, HER2 is not directly involved in control of RMS cell
growth but can be expressed at significant levels. A minority of ERMS carries a HER2 mutation
with driving activity on tumor growth. HER3 is frequently overexpressed by RMS and can play a
role in the residual myogenic differentiation ability and in resistance to signaling-directed therapy.
HER family members could be exploited for therapeutic approaches in two ways: blocking the
HER member (playing a driving role for tumor growth with antibodies or inhibitors) and targeting
expressed HER members to vehiculate toxins or immune effectors
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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