1,720,981 research outputs found
GENERATION OF TUMOR-SPECIFIC CYTOTOXIC T-LYMPHOCYTES FROM PEROPHERAL BLOOD OF COLORECTAL CANCER PATIENTS FOR ADOPTIVE T-CELL TRANSFER
Full text linkColorectal cancer (CRC) is the third most common cancer worldwide and the fourth most common cause of death in the developed Western countries.
Adoptive T-cell transfer (ACT) refers to an immunotherapeutic approach in which anti-tumor T lymphocytes, usually the tumor infiltrating lymphocytes (TIL), are identified, grown ex vivo and then re-infused into the cancer patient.
ACT of EBV-specific T-cell lines and T Cytotoxic Lymphocytes (CTLs) for the therapy of EBV-induced lymphomas is the best demonstration of clinically efficacious ACT, but there are many evidences also for leukemia and multiple myeloma.
As regards to the solid tumors, ACT using autologous TIL, grown ex-vivo and then re-infused into the cancer patient, has emerged as an effective treatment for metastatic melanoma and renal cell carcinoma (RCC), that are the most immunogenic tumors in humans. Randomized clinical trials are ongoing for gastric cancer, hepatocellular carcinoma and lung cancer.
These approaches mainly use the TIL and the definition of tumor associated antigen (TAA), tumor specific antigen (TSA) or cancer testis antigen (CTA), that are generally correlated with tumor progression and immunogenicity in various types of cancer.
However these antigens are often found to be poorly expressed in CRC, and few is known about their relationship with this type of neoplasia. In addition, although a clear association between TIL and clinical outcome of CRC has been documented, active and adoptive immunotherapy do not play yet an important role in the treatment of advanced CRC.
In order to develop an ACT protocol for CRC treatment, we designed an experimental approach that does not require neither the definition of molecular defined tumor antigens, nor the availability of TIL. Our strategy was based on the in vitro stimulation of patient’s CD8+-enriched T-cells from peripheral blood mononuclear cells (PBMCs) with dendritic cells (DCs), pulsed with apoptotic tumor cells as a source of tumor antigens, in order to generate autologous CTLs with strong anti-tumor activity.
In this study, 78 CRC patients were enrolled. Tumor biopsies were obtained at surgery, together with 100 ml of heparinized peripheral blood (PB). Tumors were mechanically dissociated to a single-cell suspension and cultured to obtain tumor cell line from each patient. DCs were generated from previously separated PBMCs, using a magnetic positive selection of CD14+ monocytes, cultured in presence of recombinant human Interleukin-4 (rh IL-4) and recombinant human Granulocyte-Macrophage Colony-Stimulating Factor (rh GM-CSF). Anti-tumor CTLs were elicited in co/micro-culture using DCs as antigen-presenting cells, autologous apoptotic tumor cells as source of antigens and T CD8+ lymphocytes enriched effectors, with weekly stimulation. CTLs Interferon-γ (IFN-γ) secretion was assessed by ELISpot assay to evaluate their activation in response to autologous tumor.
Tumor cell lines were obtained from 20 out of 78 patients (25,6%), because gut intestinal flora had adversly affected the establishment of primary tumor cell line and a loss of expansion of tumor cells was observed. DCs were generated from 26 patients, but only 6 patients had the corresponding tumor cell line, indispensable for the co-culture setting up. This was the reason why co/micro-cultures were set up only for 6 patients. ELISpot assay was performed at the end of co/micro-culture stimulations to evaluate effectors IFN-γ secretion. ELISpot results showed that strong and significant IFN-γ secretion was detected at the third, fourth and fifth stimulations for one patient and at the second for another patient, whereas for three patients a weak secretion was detected during the second and third stimulations.
Although our immunological study must be performed on an increased number of CRC patients, and the CTLs expansion, together with CTLs lytic ability against autologous tumor cells, must be still performed, our results suggested that the generation of tumor-specific CTLs could be useful for supporting an ACT approach in CRC
The long and evolving relationship between viruses and multiple sclerosis
No full textMultiple sclerosis (MS) is a demyelinating disorder of unknown etiology, possibly caused by a virus or is virus-triggered. Several viruses, including herpesviruses, were suggested as etiologic agents or risk factors for exacerbation in the course of illness but none have been shown to be irrefutably linked. Recently the interest of researchers and clinicians in the association between viruses and MS was reawakened by the development of progressive multifocal leukoencephalopathy, a demyelinating and fatal disease caused by JC polyomavirus replication, in natalizumab-treated MS patients. In this review, we will illustrate the evidence underlying the viral hypothesis for MS pathogenesis and will review the main features of the potential viral candidates. We will also describe the risks associated with newer MS therapies and with viral/bacterial vaccination
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
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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