1,721,033 research outputs found
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
In vivo hyperoxia induces hypoxia-inducible factor-1α overexpression in LNCaP tumors without affecting the tumor growth rate
No full textHypoxia is a recognized cause for solid tumors malignancy and resistance, probably via hypoxia-induced overexpression of the hypoxia-inducible factor (HIF)-1α, major modulator of the cell response to oxygen deprivation. Although hyperoxia, the opposite condition, may represent a key issue to assess this paradigm, its effect on tumor growth and HIF-1α expression remains unclear. To test whether hyperoxia and hypoxia have divergent effects, and to better focus into the role of HIF-1α in vivo, athymic mice xenografted with LNCaP cells were exposed for 28 days to atmospheres containing 10, 21 or 30% O2. Whereas the xenografts grew twice faster in hypoxia, their growth rates in hyperoxia and normoxia were similar. To analyze the involved molecular mechanisms, we performed various assays in xenograft tissues. Faster xenografts growth in hypoxia was associated with higher phosphorylation of protein kinase B (Akt) and higher expression of Ki67, both related with pro-survival and cell proliferation pathways. By contrast, the expression level of HIF-1α was similar in normoxia and hypoxia, but paradoxically twice higher in hyperoxia. The protein level of the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) was also higher in hyperoxia, suggesting marked cell response to redox imbalance. Whereas both the vascular-endothelial growth factor (VEGF) and its receptor VEGF-R2 were overexpressed in hyperoxia, the tissue hemoglobin content was not increased, despite a slight reduction in vascularization. As a whole, this data indicates that the xenografts growth rate was independent of HIF-1α expression level, suggesting that in an in vivo setting alternative more effective proliferative paths associated with the cell response to the redox imbalance may override the paths linked to HIF-1α signaling
Resveratrol : a potential challenger against gastric cancer
No full textGastric cancer (GC) is the fourth most common cancer and the second leading cause of cancer-related mortality in the world. Late diagnosis and classical therapeutic approaches such as surgery, chemotherapy and radiotherapy make this disease a still threatening tumor. Genetic asset, environmental stress, dietary habit and infections caused by Helicobacter pylori (H. pylori) are the major causes concurring to GC initiation. A common mechanism is induction of radicals resulting in gastric mucosal injury. A regular food intake of antioxidant and radical scavenging agents has been proposed to exert protection against tumorigenesis. Resveratrol belongs to the polyphenol flavonoids class of antioxidants produced by a restricted number of plants. Resveratrol exerts bactericidal activity against H. pylori and is a powerful antioxidant, thus acting as a tumor preventive agent. Resveratrol intracellular signaling results in growth arrest and apoptosis, so that it can be directed against tumor progression. Resveratrol therapeutic potential against GC initiation and progression are reviewed here
Chronic systemic hypoxia promotes LNCaP prostate cancer growth in vivo
No full textOBJECTIVE. Solid tumors contain underperfused regions where hypoxia-inducible factor-1α (HIF-1α) over-expression induces hypoxia adaptation and cell proliferation. We test the hypothesis that systemic hypoxia promotes prostate cancer growth in vivo and examine HIF-1α centrality in this effect. METHODS. Male athymic mice were xenografted with 3 × 10 6 LNCaP cells per each flank and exposed for 28 days to either chronic hypoxia (CH, 10% O2) or CH with reoxygenation (CHReox, 3 times/week for 1 hr), with normoxia as control (n = 17, 9, and 20, respectively). At the end of the observation, mice were euthanized and tumors harvested for analyses. RESULTS. The successful xenografts grew faster in CH and CHReox than in normoxia (first-order rate constants 0.15 ± 0.01, 0.18 ± 0.03, and 0.09 ± 0.01 day-1, P < 0.05, n = 18, 15, and 25, respectively). Furthermore, the tumor masses at the end were 4.09 ± 0.58, 3.42 ± 0.55, and 1.86 ± 0.25 mg/g bw (P < 0.05), respectively. HIF-1α, assayed by Western blot and immunofluorescence, was slightly increased in CH with respect to normoxia, but markedly overexpressed (5-10 times) in CHReox (P < 0.001). The tumor hemoglobin content, higher in CH and CHReox than in normoxia, reflected the higher blood hemoglobin concentration, not neovascularization, as supported by similar expression levels of vascular endothelial growth factor (VEGF) in the three groups. By contrast, protein kinase B (Akt) was more phosphorylated in both hypoxic groups than in normoxia (P < 0.01). CONCLUSION. In vivo systemic hypoxia promotes prostate cancer growth regardless of HIF-1α expression level and neovascularization, suggesting an important role for hypoxia-dependent pathways that do not involve HIF-1α, as the phosphatidyl inositol-3-phosphate signaling cascade
Camera per la stabulazione di piccoli mammiferi, destinata allo studio degli effetti della permanenza cronica in atmosfere alterate e ipossia
No full textSi descrive un dispositivo a camera di stabulazione in atmosfere normobariche alterarte per lo studio su modelli in vivo degli effetti della permanenza di piccoli mammiferi in atmosfera alterata
In vivo up-regulation of the unfolded protein response after hypoxia
No full textBACKGROUND: Low oxygen (O(2)) availability, a condition called hypoxia, has different and profound consequences in tissues and organs. Besides the hypoxia-inducible response, mammalian cells induce a coordinated cytoprotective pathway called Unfolded Protein Response (UPR). We studied the molecular basis of UPR and apoptosis in animal models exposed to different hypoxic stresses and assessed the ability of liver and myocardium to respond to low oxygen by activating different arms of the UPR according to the severity of the insults in a tissue specific manner. METHODS: We assessed the levels of several UPR markers in hypoxic animals by Real Time PCR and Western blotting. RESULTS: While the hepatocytes activate the apoptotic pathway mediated, in part, by CHOP and p-JNK, we could not detect an UPR-dependent apoptosis in myocytes. Moreover, severe hypoxia results in ATF4 translation, and induction of CHOP and GADD34 transcripts in liver, by contrast in the myocardium, the ATF4-CHOP-GADD34 signaling pathway is not detectably activated. GENERAL SIGNIFICANCE: Comparison of several UPR markers in liver and myocardium enabled to underscore the ability of hepatocytes and myocites to selectively activate and fine tune the UPR signaling pathway during hypoxia in vivo
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