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De Luca A Gallo M Aldinucci D Ribatti D Lamura L D'Alessio A De Filippi R Pinto A Normanno N 《Journal of cellular physiology》2011,226(8):2131-2138
Increasing evidence suggests that bone marrow-derived mesenchymal stem cells (MSCs) are recruited into the stroma of developing tumors where they contribute to cancer progression. MSCs produce different growth factors that sustain tumor-associated neo-angiogenesis. Since the majority of carcinomas secrete ligands of the epidermal growth factor receptor (EGFR), we assessed the role of EGFR signaling in regulating the release of angiogenic factors in MSCs. Treatment of human primary MSCs and of the human osteoblastic cell line hFOB with transforming growth factor α (TGF-α), one of the main ligands of the EGFR, significantly induced activation of this receptor and of different intracellular signaling proteins, including the PI3K/AKT and the MEK/MAPK pathways. TGF-α induced a significant increase in the levels of secretion of vascular endothelial growth factor in both MSCs and hFOB. Conditioned medium from TGF-α treated MSCs showed an higher in vivo angiogenic effect as compared with medium from untreated cells. Treatment of MSCs with TGF-α also produced a significant increase in the secretion of other angiogenic growth factors such as angiopoietin-2, granulocyte-colony stimulating factor, hepatocyte growth factor, interleukin (IL)-6, IL-8, and platelet-derived growth factor-BB. Using selective MEK and PI3K inhibitors, we found that both MEK/MAPK and the PI3K/AKT signaling pathways mediate the ability of TGF-α to induce secretion of angiogenic factors in MSCs. Finally, stimulation with TGF-α increased the ability of MSCs to induce migration of MCF-7 breast cancer cells. These data suggest that EGFR signaling regulates the ability of MSCs to sustain cancer progression through the release of growth factors that promote neo-angiogenesis and tumor cell migration. 相似文献
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Luana Lionetto Martina Ulivieri Matilde Capi Donatella De Bernardini Francesco Fazio Andrea Petrucca Leda Marina Pomes Ottavia De Luca Giovanna Gentile Barbara Casolla Martina Curto Gerardo Salerno Serena Schillizzi Maria Simona Torre Iolanda Santino Monica Rocco Paolo Marchetti Antonio Aceti Marina Borro 《生物化学与生物物理学报:疾病的分子基础》2021,1867(3):166042
Immune dysregulation is a hallmark of patients infected by SARS-CoV2 and the balance between immune reactivity and tolerance is a key determinant of all stages of infection, including the excessive inflammatory state causing the acute respiratory distress syndrome. The kynurenine pathway (KP) of tryptophan (Trp) metabolism is activated by pro-inflammatory cytokines and drives mechanisms of immune tolerance. We examined the state of activation of the KP by measuring the Kyn:Trp ratio in the serum of healthy subjects (n = 239), and SARS-CoV2-negative (n = 305) and -positive patients (n = 89). Patients were recruited at the Emergency Room of St. Andrea Hospital (Rome, Italy). Kyn and Trp serum levels were assessed by HPLC/MS-MS. Compared to healthy controls, both SARS-CoV2-negative and -positive patients showed an increase in the Kyn:Trp ratio. The increase was larger in SARS-CoV2-positive patients, with a significant difference between SARS-CoV2-positive and -negative patients. In addition, the increase was more prominent in males, and positively correlated with age and severity of SARS-CoV2 infection, categorized as follows: 1 = no need for intensive care unit (ICU); 2 ≤ 3 weeks spent in ICU; 3 ≥ 3 weeks spent in ICU; and 4 = death. The highest Kyn:Trp values were found in SARS-CoV2-positive patients with severe lymphopenia. These findings suggest that the Kyn:Trp ratio reflects the level of inflammation associated with SARS-CoV2 infection, and, therefore, might represent a valuable biomarker for therapeutic intervention. 相似文献
5.
Marcelo de Oliveira Barbosa Rubens Rodrigues da Silva Vanessa Carolina de Sena Correia Luana Pereira dos Santos Analía del Valle Garnero Ricardo José Gunski 《Genetics and molecular biology》2013,36(1):70-73
Cytogenetic studies in birds are still scarce compared to other vertebrates. Woodcreepers (Dendrocolaptidae) are part of a highly specialized group within the Suboscines of the New World. They are forest birds exclusive to the Neotropical region and similar to woodpeckers, at a comparable evolutionary stage. This paper describes for the first time the karyotypes of the Olivaceous and the Narrow-billed Woodcreeper using conventional staining with Giemsa and silver nitrate staining of the nucleolar organizer regions (Ag-NORs). Metaphases were obtained by fibular bone marrow culture. The chromosome number of the Olivaceous Woodcreeper was 2n = 82 and of the Narrow-billed Woodcreeper, 2n = 82. Ag-NORs in the largest macrochromosome pair and evidence of a chromosome inversion are described herein for the first time for this group. 相似文献
6.
Luigi Ornano Alessandro Venditti Mauro Ballero Cinzia Sanna Luana Quassinti Massimo Bramucci Giulio Lupidi Fabrizio Papa Sauro Vittori Filippo Maggi Armanodoriano Bianco 《化学与生物多样性》2013,10(8):1464-1474
The essential oils of Artemisia arborescens growing in Sardinia (Italy), collected during three plant growth stages, i.e., from the vegetative stage to post‐blooming time, were characterized. Moreover, the in vitro antiproliferative and antioxidant activities of the oil isolated from aerial parts collected in February were evaluated. The essential oils belonged to the β‐thujone/chamazulene chemotype, notably with the highest amount of chamazulene (ca. 52%) ever detected up to now in the genus Artemisia and, in general, in essential oils. Quantitative variations in the oil composition were observed as the plant passes from the vegetative to the blooming stage. The oil was tested for its potential tumor cell growth‐inhibitory effect on T98G, MDA‐MB 435S, A375, and HCT116 human cell lines, using the MTT (=3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl‐2H‐tetrazolium bromide) assay. The highest activity was observed on A375 and HCT116 cell lines, with IC50 values of 14 μg/ml. Moreover, the in vitro antioxidant and free radical‐scavenging assays revealed the oil to be an effective scavenger of the ABTS radical cation, with an activity comparable to that of Trolox®. These results support the use of A. arborescens oil for the treatment of inflamed skin conditions. Finally, the composition of the polar fraction of the A. arborescens aerial parts was also examined, and the main component detected was 5‐O‐caffeoylquinic acid, which was identified for the first time in this plant. 相似文献
7.
Anna Maria Di Giacomo Luana Calabrò Riccardo Danielli Ester Fonsatti Erica Bertocci Isabella Pesce Carolina Fazio Ornella Cutaia Diana Giannarelli Clelia Miracco Maurizio Biagioli Maresa Altomonte Michele Maio 《Cancer immunology, immunotherapy : CII》2013,62(6):1021-1028
Background
Ipilimumab can result in durable clinical responses among patients with advanced melanoma. However, no predictive marker of clinical activity has yet been identified. We provide preliminary data describing the correlation between immunological parameters and response/survival among patients with advanced melanoma who received ipilimumab 10 mg/kg in an expanded access programme.Methods
Patients received ipilimumab 10 mg/kg every 3 weeks (Q3W) for four doses (induction) and Q12W from week 24 (W24) as maintenance therapy. Tumor assessments were conducted Q12W. Expression of inducible T cell costimulator (ICOS) on CD4+ and CD8+ T cells was assessed at baseline, W7, W12 and W24, and the ratio between absolute neutrophils (N) and lymphocytes (L) determined at baseline, W4, W7 and W10.Results
Median overall survival among 27 patients was 9.6 months (95 % CI 3.2–16.1), with 3- and 4-year survival rates of 20.4 %. Five patients survived >4 years. Patients with an increase in the number of circulating ICOS+ T cells at W7 were more likely to experience disease control and have improved survival. An N/L ratio below the median at W7 and W10 was also associated with better survival compared with an N/L ratio above the median.Conclusions
Ipilimumab can induce long-term survival benefits in heavily pretreated patients with metastatic melanoma. Changes in the number of circulating ICOS+ T cells or N/L ratio during ipilimumab treatment may represent early markers of response. However, given the limited sample size, further investigation is required. 相似文献8.
Jaqueline Raymondi Silva Larissa Campos de Medeiros Vinícius Pinho dos Reis Juliana Helena Chávez Thiago Demarchi Munhoz Gustavo Puia Borges Otavio Augusto Brioschi Soares Carlos Henrique Coelho de Campos Rosangela Zacarias Machado Cristiane Divan Baldani Maria Luana Cristiny Rodrigues Silva Joice Lara Maia Faria Edson Elias da Silva Luiz Tadeu Moraes Figueiredo 《Memórias do Instituto Oswaldo Cruz》2013,108(7):921-923
Since the emergence of West Nile virus (WNV) in North America in 1999, there have been several reports of WNV activity in Central and South American countries. To detect WNV in Brazil, we performed a serological survey of horses from different regions of Brazil using recombinant peptides from domain III of WNV. Positive samples were validated with the neutralisation test. Our results showed that of 79 ELISA-positive horses, nine expressed WNV-specific neutralising antibodies. Eight of the infected horses were from the state of Mato Grosso do Sul and one was from the state of Paraíba. Our results provide additional evidence for the emergence of WNV in Brazil and for its circulation in multiple regions of the country. 相似文献
9.
Danielly Beraldo dos Santos Silva Luana Mireli Carbonera Rodrigues Adriana Araújo de Almeida Kelly Mari Pires de Oliveira Alexéia Barufatti Grisolia/ 《Memórias do Instituto Oswaldo Cruz》2016,111(3):192-199
The azoles are the class of medications most commonly used to fight infections caused
by Candida sp. Typically, resistance can be attributed to mutations
in ERG11 gene (CYP51) which encodes the cytochrome P450
14α-demethylase, the primary target for the activity of azoles. The objective of this
study was to identify mutations in the coding region of theERG11
gene in clinical isolates of Candidaspecies known to be resistant to
azoles. We identified three new synonymous mutations in the ERG11
gene in the isolates of Candida glabrata (C108G, C423T and A1581G)
and two new nonsynonymous mutations in the isolates of Candida
krusei - A497C (Y166S) and G1570A (G524R). The functional consequence of
these nonsynonymous mutations was predicted using evolutionary conservation scores.
The G524R mutation did not have effect on 14α-demethylase functionality, while the
Y166S mutation was found to affect the enzyme. This observation suggests a possible
link between the mutation and dose-dependent sensitivity to voriconazole in the
clinical isolate of C. krusei. Although the presence of the Y166S in
phenotype of reduced azole sensitivity observed in isolate C.
kruseidemands investigation, it might contribute to the search of new
therapeutic agents against resistant Candida isolates. 相似文献
10.
Territory Availability at Different Spatial Scales does not Affect Fighting Investment in Males of the Lycaenid Butterfly Strymon mulucha
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Cibele P. S. Ferreira Luana P. Cerqueira Alexandre Uezu Eddy J. F. Oliveira Paulo E. C. Peixoto 《Ethology : formerly Zeitschrift fur Tierpsychologie》2016,122(10):798-806
In territorial species, rivals investment in fights over territories may increase when the availability of suitable areas for defense is low. This should occur because low territory availability may increase the costs to maintain and acquire territories. Although such process occurs in small spatial scales (local scale), territory availability in larger scales (regional scale) may also affect fighting investment, as losers should incur additional dispersing costs to find new territories. In this study, we used males of the hilltopping butterfly Strymon mulucha to evaluate the hypothesis that males should invest more in territorial fights when the costs to find new territories are higher (both at local and at regional scale). We timed male–male contests for territories located in 12 hilltops and measured male density per territory in each hilltop (local scale). We also quantified the distance between hilltops containing suitable areas for territories (regional scale). Male–male contests lasted 21 s on average, and copulations did not occur during the observations. The duration of contests was unrelated to the male density per territory or to the distance among hilltops, indicating that the investment in fights was unaffected by the availability of territorial sites, independent of the spatial scale. As male–male contests in S. mulucha are longer than the mean contest duration in other butterfly species and mating is extremely rare, we suggest that the value of each territory may be high enough to favor males that always invest as much as possible in contests. 相似文献