1,721,076 research outputs found
Combined and sequential expression of p53, Rb, Ras and Bcl-2 in bronchial preneoplastic lesions
No full textAims and background: Several simple molecular abnormalities have been detected rn bronchial preneoplastic lesions, but the simultaneous presence of these alterations has been scarcely investigated. Methods: We studied, by an immunohistochemical method, the expression of p53, Rb, Ras and Bcl-2 in 65 samples from surgical specimens and diagnostic biopsies selected for the presence of preneoplastic changes in the bronchial epithelium. To perform an analysis of the combined expression of all markers in the same areas, we accurately mapped every consecutive section on which immunohistochemical reactions were performed, subdividing each specimen into 25x microscopic fields, which allowed good topographical mapping. Results: It was found that the frequency of p53-positive and Rb-negative microscopic fields was directly related to the morphological grading of lesions. On the other hand, Ras expression characterized high-grade lesions not Showing squamous differentiation (non-squamous Cis). Regarding Bcl-2 expression, only slight differences in positivity distribution were found between the different lesions. More interesting was the parallel evaluation of all markers in the same areas: one of the main patterns, found to be correlated with the severity of histopathological features, was characterized by combined p53 hyperexpression/Rb hypoexpression; furthermore, when Ras and Bcl-2 hyperexpression were superimposed to the above pattern, the former mainly characterized non-squamous Cis, while the latter was present only in high-grade squamous lesions. However, the most frequently encountered pattern did not show any alteration of the studied markers, suggesting that other mechanisms could be involved in bronchial carcinogenesis. Conclusions: The detection of combined molecular abnormalities in bronchial preneoplasia could clarify the steps involved in lung carcinogenesis; furthermore, a simple and inexpensive method, such as immunohistochemistry, could be routinely applied also to cytologic specimens in order to detect those lesions, or patients, that are prone to progression towards lung cancer
Correspondence re: Samowitz et al., Microsatellite instability in sporadic colon cancer is associated with an improved prognosis at the population level. Cancer Epidemiol. Biomark. Prev., 10 : 917-923, 2001
No full textNo abstract availabl
Infectious agents in mucosa-associated lymphoid tissue-type lymphomas: Pathogenic role and therapeutic perspectives
No full textMucosa-associated lymphoid tissue (MALT) lymphoma probably constitutes the best in vivo model showing how complex interplay between B lymphocytes and the surrounding microenvironment may lead to a neoplastic disorder. After the seminal discovery of the pathogenic association between Helicobacter pylori and gastric MALT lymphomas, evidence suggests the possible involvement of other infectious agents in the development of MALT lymphomas arising at different body sites. Although several other bacteria (Borrelia burgdorferi, Campylobacter jejuni, and Chlamydia psittaci) and viruses (Hepatitis C virus) seem to play a role in lymphomas presenting at different locations, a possible common pathogenic mechanism is emerging. Several lines of evidence suggest that different infectious agents might provide a chronic antigenic stimulation that elicits host immune responses able to promote clonal B-cell expansion. This model is also substantiated by the increasing number of patients with MALT lymphomas who exhibit objective clinical responses after antimicrobial therapy. A multidisciplinary approach is critical to better understand the complex etiopathogenesis of MALT lymphomas with the final goal to dissect the clinicopathologic heterogeneity of these disorders and design more tailored preventive and therapeutic approaches
Activation of infiltrating cytotoxic T lymphocytes and lymphoma cell apoptotic rates in gastric MALT lymphomas - Differences between high-grade and low-grade cases
No full textIn this study, we have characterized infiltrating T lymphocytes from 13 low-grade and 17 high-grade primary gastric MALT lymphomas by immunohistochemistry, with particular regard to the presence, activation, and topographic distribution of cytotoxic effecters. Although the prevalence of CD4+ and CD8+ cells was similar in low- and high-grade lymphomas, higher numbers of TIA-1+ cytotoxic effecters were found in this latter group of cases (11.6 versus 7.8%; P = 0.004), Activation of CD8+ cytotoxic T lymphocytes (CTLs) was significantly more pronounced in high than in low-grade lymphomas, as shown by immunostaining for perforin (8.7 versus 4.0%; P = 0.001) and granzyme-B (GrB) (8.7% versus 3.0%; P < 0.0001), Of note, CD20/GrB double labeling showed that high-grade lymphomas carried a markedly higher content (about ninefold) of activated CTLs relative to the number of CD20+ lymphoma B cells (0.081 +/- 0.076 versus 0.009 +/- 0.011; P < 0.0001). Moreover, high-grade lymphomas showed significantly increased apoptotic rates compared to low grade cases (5.3 and 1.1% of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive cells, respectively; P < 0.0001). In the whole series, the percentage of GrB+ cells and the GrB+/CD20+ ratio showed a strong Linear correlation with the number of TUNEL-labeled cells. These findings, together with the frequent colocalization of CTLs and TUNEL+ neoplastic cells, suggested that apoptotic death of lymphoma cells may be due at least in part to the killing by cytotoxic effecters. Our results are consistent with the occurrence of host antitumor cell-mediated immune responses in gastric MALT lymphomas, Moreover, the finding of stronger cytotoxic responses in high than in low-grade cases is of potential usefulness in the design of more effective therapeutic strategies for the management of these disorders.In this study, we have characterized infiltrating T lymphocytes from 13 low-grade and 17 high-grade primary gastric MALT lymphomas by immunohistochemistry, with particular regard to the presence, activation, and topographic distribution of cytotoxic effectors. Although the prevalence of CD4+ and CD8+ cells was similar in low- and high-grade lymphomas, higher numbers of TIA-1+ cytotoxic effectors were found in this latter group of cases (11.6 versus 7.8%; P = 0.004). Activation of CD8+ cytotoxic T lymphocytes (CTLs) was significantly more pronounced in high- than in low- grade lymphomas, as shown by immunostaining for perforin (8.7 versus 4.0%; P = 0.001) and granzyme-B (GrB) (8.7% versus 3.0%; P < 0.0001). Of note, CD20/GrB double labeling showed that high-grade lymphomas carried a markedly higher content (about ninefold) of activated CTLs relative to the number of CD20+ lymphoma B cells (0.081 ± 0.076 versus 0.009 ± 0.011; P < 0.0001). Moreover, high-grade lymphomas showed significant..
Malignant Pleural Mesothelioma: State-of-the-Art on Current Therapies and Promises for the Future
Full text linkMalignant pleural mesothelioma (MPM) is a rare, aggressive cancer of the pleural surface associated with asbestos exposure. The median survival of MPM patients is a mere 8–14 months, and there are few biomarkers and no cure available. It is hoped that, eventually, the incidence of MPM will drop and remain low and constant, given that most nations have banned the use of asbestos, but in the meantime, the incidence in Europe is still growing. The exact molecular mechanisms that explain the carcinogenicity of asbestos are not known. Standard therapeutic strategies for MPM include surgery, often coupled with chemotherapy and/or radiotherapy, in a small percentage of eligible patients and chemotherapy in tumors considered unresectable with or without adjuvant radiotherapy. In recent years, several new therapeutic avenues are being explored. These include angiogenesis inhibitors, synthetic lethal treatment, miRNA replacement, oncoviral therapies, and the fast-growing field of immunotherapy alone or in combination with chemotherapy. Of particular promise are the multiple options offered by immunotherapy: immune checkpoint inhibitors, tumor vaccines, and therapies taking advantage of tumor-specific antigens, such as specific therapeutic antibodies or advanced cell-based therapies exemplified by the CAR-T cells. This review comprehensively presents both old and new therapeutic options in MPM, focusing on the results of the numerous recent and on-going clinical trials in the field, including the latest data presented at international meetings (AACR, ASCO, and ESMO) this year, and concludes that more work has to be done in the framework of tailored therapies to identify reliable targets and novel biomarkers to impact MPM management
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
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