1,721,171 research outputs found
Determination of angiogenesis in human neoplasms: Current prognostic and therapeutic implications
The growth of solid tumours beyond a certain mass is strictly dependent on the formation of a vascular bed from a pre-existing host vasculature. This process has been termed 'angiogenesis' and its importance in the process of tumour growth and metastasis has recently gained wide acceptance. Studies have been reported in several kinds of human cancers in which the number of microvessels in the most intense areas of neo-vascularisation ('hot spots') have been shown to be strictly related to the development and progression of the tumour. In the majority of these studies highly vascularised tumours showed a poor prognosis and the influence of tumour angiogenesis proved to be independent of conventional prognostic indicators. The evaluation of tumour angiogenesis by quantitative pathology may represent an important prognostic indicator in human cancers and will be increasingly important in the investigation of new therapies directed to inhibiting angiogenesis or targeting tumour vasculature. This review will briefly summarise the current knowledge on the prognostic impact of tumour angiogenesis in human cancers with a final reference to angiogenesis inhibitors which are currently used in phase I/II and III clinical trials
Reciprocal interference between milk-transmitted mammary tumor virus and Friend leukemia viruses in mice: possible role of the interferon system
Distinct Angiogenic microRNA-mRNA Expression Profiles Among Subtypes of Lung Adenocarcinoma.
denocarcinoma (ADC) represents the most common histological type of non-small cell lung cancer (NSCLC), with a heterogeneous pattern of growth classified as lepidic, acinar, papillary, solid, and micropapillary. For ADC patients there are few available therapeutic options and a valuable therapeutic strategy is represented by angiogenesis inhibitors; however, new reliable biomarkers to identify patients with benefit from anti-angiogenic drugs are needed. We designed a panel of sixteen miRNAs together with six their mRNA targets involved in the angiogenesis pathway and expression analysis was performed by the nCounter System® (NanoString Technologies) in 88 ADC patients: 29 were predominantly lepidic (33%), 26 solid (29.5%), 22 acinar (25%), and for 11 patients the prevalent pattern was papillary (12.5%). When we compared mRNA expression levels with the different histological ADC subtypes we found a significant higher expression of VEGF in papillary and solid than in other subtypes (p = 0.008). Among 16 miRNAs that target the angiogenic mRNA, 4 were significantly downregulated in papillary/solid compared to other groups. Our data suggest a distinct angiogenic miRNA-mRNA expression profile among the subtypes of ADC, with a putative clinical application to stratify patients for anti-angiogenetic drugs. Moreover, the regulation of angiogenic mRNA factors by miRNAs could provide a novel therapeutic approach based on their expression pattern specific for distinct ADC subtypes. Further studies are needed in a larger cohort of patients to confirm our results
Fr-MLV infection induces erythroleukaemia instead of lymphoid leukaemia in mice given pituitary grafts
Lung colonization and metastasis of murine mammary tumors: relationship to various characteristics of the primary tumors
The ability to metastasize via the bloodstream of mammary tumors occurring in Balb/cfC3H and Balb/cfRIII mice (two substrains of identical Balb/c genotype carrying milk-transmitted C3H or RIII murine mammary tumor virus (MuMTV) infection, respectively) has been compared in MuMTV-free Balb/c virgin female recipients given intravenous tumor cell suspensions or subcutaneous solid tumor transplants from mammary tumor-bearing Balb/cfC3H and Balb/cfRIII breeding female donors. Tumor cell suspensions different for MuMTV inducing variant, growth rate, tumor size, and clinical duration, injected intravenously to Balb/c virgin female recipients, have been compared with respect to the foci of lung colonization induced in recipient hosts. The results obtained indicate that MuMTV variant, growth rate and clinical duration of the primary mammary tumor, but not the size of the primary tumor, significantly influence the lung colonization. Similar results were obtained with solid subcutaneous transplants of the same mammary tumors. The significance of these results for the understanding of the general mechanisms of tumor metastases is discussed
Expression profiling and microRNA regulation of the LKB1 pathway in young and aged lung adenocarcinoma patients
Lung cancer in young patients appears to have distinct clinicopathological features. The present study focused on the role of the serine/threonine kinase liver kinase B1 (LKB1), a known tumor suppressor gene, and its miRNA regulation in lung adenocarcinoma, particularly in young versus elderly patients. A total of 88 patients with lung adenocarcinoma were retrospectively analysed. A simultaneous quantification was performed of the expression of LKB1 mRNA and 15 microRNAs (miRNA/miRs; miRs -93, -96, -34a, -34c, -214, -33a, -30b, -145, -182, -30c, -183, -29b, -29c, -153 and -138) involved in the LKB1 pathway, as well as of 5 identified target mRNAs [cyclin D1 (CCND1), catenin β-1 (CTNNB1), lysyl oxidase (LOX), yes-associated protein 1 (YAP1) and survivin], using NanoString technology. KRAS mutations were investigated by pyrosequencing analysis. Patients ≤50 years were defined as a younger group, while patients >50 years old as an older group (n=44/group). No difference between the two groups was identified in terms of survival times analysed using the Kaplan-Meier method or KRAS mutations. Subsequently, the LKB1 signalling pathway was focused on, as a target for therapy in lung adenocarcinoma, and assessed with regards to clinicopathological features; we found that LOX levels in adenocarcinoma patients were significantly associated with histological subtype (P=0.03), stage (P<0.0001) and prognosis (P=0.02 for disease-free interval and P=0.005 for overall survival), but not with age. Furthermore, the miRNA target prediction model indicated that miR-93 and miR-30b appeared to have functional binding sites and downregulate the gene expression of LKB1 and LOX, respectively. In conclusion, young patients appeared have similar survival rates to elderly patients. The assessment of LKB1, its downstream genes and its regulation by miRNAs may have an impact on future research on lung adenocarcinoma in young and elderly patients. Further investigations will be necessary to elucidate the potential of this pathway as a novel target for therapy
Going Beyond Counting First Authors in Author Co-citation Analysis
The 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
“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
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