214 research outputs found
Co-targeting the IGF system and HIF-1 inhibits migration and invasion by (triple-negative) breast cancer cells
BACKGROUND:
Metastatic triple-negative breast cancer is mostly incurable, due to lack of suitable drug targets. The insulin-like growth factor (IGF) system could provide such a target, and IGF-1 receptor (IGF-1R)-directed agents are already available, but seem unable to control all the complexities of the system, including crosstalk with hypoxia-inducible pathways.
METHODS:
Migration of triple-negative MDA-231 breast cancer cells and its modulation by IGFs, the IGF-1R inhibitor NVP-AEW541 and the IGF-2-sequestering monoclonal antibody MAB292 were assessed by the scratch wound healing and Boyden chamber assays; the effect of topotecan (inhibiting hypoxia-inducible factor-1 (HIF-1)) under hypoxia was also evaluated. Constitutive as well as drug-modulated levels of components of the IGF and HIF-1 pathways were evaluated by western blotting and qPCR.
RESULTS:
IGF-induced migration of MDA-231 cells was not abrogated by the IGF-1R inhibitor NVP-AEW541, whereas IGF-2 sequestration by MAB292 significantly reduced cell migration. Under hypoxia, topotecan was also effective, likely by reducing HIF-1-induced IGF-2 release. Simultaneous targeting of IGF-1R and IGF-2 or HIF-1 completely abolished cell migration.
CONCLUSIONS:
IR activation may account for the failure of NVP-AEW541 to suppress MDA-231 cell migration. Ligand-targeting compounds, or co-inhibition of the IGF and HIF-1 systems, may prevent activation of compensatory signalling, thereby providing a valuable addition to IGF-1R inhibitor-based therapies
Study of the characteristic parameters of the normal voices of Argentinian speakers
The voice laboratory permits to study the human voices using a method that is objective and noninvasive. In this work, we have studied the parameters of the human voice such as pitch, formant, jitter, shimmer and harmonic-noise ratio of a group of young people. This statistical information of parameters is obtained from Argentinian speakers.publishedVersionFil: Bonzi, Edgardo Venusto. Universidad Nacional de CĂłrdoba. Facultad de MatemĂĄtica, AstronomĂa y FĂsica; Argentina.Fil: Bonzi, Edgardo Venusto. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Instituto de FĂsica Enrique Gaviola; Argentina.Fil: Grad, G. B. Universidad Nacional de CĂłrdoba. Facultad de MatemĂĄtica, AstronomĂa y FĂsica; Argentina.Fil: Maggi, A. M. Universidad Nacional de CĂłrdoba. Facultad de Ciencias MĂ©dicas. Escuela de FonoaudiologĂa; Argentina.Fil: Muñóz, M. R. Universidad Nacional de CĂłrdoba. Facultad de Ciencias MĂ©dicas. Escuela de FonoaudiologĂa; Argentina.Otras Ciencias FĂsica
Perception paysanne et impact agro-pédologique du niveau de mécanisation agricole dans les zones cotonniÚres Centre et Ouest du Burkina Faso
Au Burkina Faso, la production cotonniĂšre est assurĂ©e par un travail du sol Ă traction animale ou motorisĂ©e. Les sols assurant lâessentiel de cette production sont soit ferralitiques (Ă lâOuest) soit ferrugineux tropicaux (au Centre). Pour Ă©valuer lâimpact socio-Ă©conomique et agro-pĂ©dologique du type dâexploitation, des enquĂȘtes (interviews semi-structurĂ©s et Ă©valuation participative) ont Ă©tĂ© rĂ©alisĂ©es sur un Ă©chantillon de 315 exploitants et des mesures agro-pĂ©dologiques rĂ©alisĂ©es sur 140 champs dans les 2 zones cotonniĂšres. Les rĂ©sultats ont montrĂ© un faible niveau de mĂ©canisation gĂ©nĂ©rale et trois groupes dâexploitants : les grands exploitants (type E1) qui disposent de grands moyens de productions, les exploitants moyens (type E2) et les petits exploitants (type E3) ayant de faibles revenus. Aussi, une proportionnalitĂ© existe entre les facteurs de production dâune exploitation et la catĂ©gorie socioprofessionnelle de lâexploitant. LâĂ©valuation participative de lâimpact des rĂ©gimes de travail du sol sur les paramĂštres agronomiques et sur le sol a montrĂ© des perceptions divergentes en fonction de la zone de production. Sur les paramĂštres agronomiques les paysans des deux zones sont unanimes sur le fait que le travail profond du sol en traction animale ou motorisĂ©e permet dâamĂ©liorer les propriĂ©tĂ©s hydrodynamiques du sol et par consĂ©quent entraine une bonne levĂ©e et une meilleure production des cultures. Quant Ă lâimpact de la mĂ©canisation agricole sur la fertilitĂ© du sol, les paysans de la zone Ouest Ă pluviositĂ© > 900 mm et sur sols ferralitiques prĂ©conisent un travail minimum du sol. Tandis que ceux de la zone Ă pluviositĂ© entre 700-900 mm et sur sols ferrugineux tropicaux recommandent le travail profond qui permettrait la rĂ©cupĂ©ration des terres encroĂ»tĂ©s. Ces perceptions sont effectivement confirmĂ©es par les analyses agronomiques et pĂ©doclimatiques faites dans les mĂȘmes milieux. Pour une gestion durable des terres, il faut une intervention concertĂ©e avec les paysans. En outre les moyens de production doivent ĂȘtre vulgarisĂ©s en fonction des conditions pĂ©doclimatiques de chaque zone.Mots clĂ©s: Impacts socio-Ă©conomiques, mĂ©canisation agricole, rendements, sol, zones cotonniĂšres, Burkina Faso
Sexâ and timeâspecific parental effects of warming on reproduction and offspring quality in a coral reef fish
Global warming can disrupt reproduction or lead to fewer and poorer quality offspring, owing to the thermally sensitive nature of reproductive physiology. However, phenotypic plasticity may enable some animals to adjust the thermal sensitivity of reproduction to maintain performance in warmer conditions. Whether elevated temperature affects reproduction may depend on the timing of exposure to warming and the sex of the parent exposed. We exposed male and female coral reef damselfish (Acanthochromis polyacanthus) during development, reproduction or both life stages to an elevated temperature (+1.5°C) consistent with projected ocean warming and measured reproductive output and newly hatched offspring performance relative to pairs reared in a present-day control temperature. We found female development in elevated temperature increased the probability of breeding, but reproduction ceased if warming continued to the reproductive stage, irrespective of the male\u27s developmental experience. Females that developed in warmer conditions, but reproduced in control conditions, also produced larger eggs and hatchlings with greater yolk reserves. By contrast, male development or pairs reproducing in higher temperature produced fewer and poorer quality offspring. Such changes may be due to alterations in sex hormones or an endocrine stress response. In nature, this could mean female fish developing during a marine heatwave may have enhanced reproduction and produce higher quality offspring compared with females developing in a year of usual thermal conditions. However, male development during a heatwave would likely result in reduced reproductive output. Furthermore, the lack of reproduction from an average increase in temperature could lead to population decline. Our results demonstrate how the timing of exposure differentially influences females and males and how this translates to effects on reproduction and population sustainability in a warming world
Parents exposed to warming produce offspring lower in weight and condition
The parental environment can alter offspring phenotypes via the transfer of non-genetic information. Parental effects may be viewed as an extension of (within-generation) phenotypic plasticity. Smaller size, poorer physical condition, and skewed sex ratios are common responses of organisms to global warming, yet whether parental effects alleviate, exacerbate, or have no impact on these responses has not been widely tested. Further, the relative non-genetic influence of mothers and fathers and ontogenetic timing of parental exposure to warming on offspring phenotypes is poorly understood. Here, we tested how maternal, paternal, and biparental exposure of a coral reef fish (Acanthochromis polyacanthus) to elevated temperature (+1.5°C) at different ontogenetic stages (development vs reproduction) influences offspring length, weight, condition, and sex. Fish were reared across two generations in present-day and projected ocean warming in a full factorial design. As expected, offspring of parents exposed to present-day control temperature that were reared in warmer water were shorter than their siblings reared in control temperature; however, within-generation plasticity allowed maintenance of weight, resulting in a higher body condition. Parental exposure to warming, irrespective of ontogenetic timing and sex, resulted in decreased weight and condition in all offspring rearing temperatures. By contrast, offspring sex ratios were not strongly influenced by their rearing temperature or that of their parents. Together, our results reveal that phenotypic plasticity may help coral reef fishes maintain performance in a warm ocean within a generation, but could exacerbate the negative effects of warming between generations, regardless of when mothers and fathers are exposed to warming. Alternatively, the multigenerational impact on offspring weight and condition may be a necessary cost to adapt metabolism to increasing temperatures. This research highlights the importance of examining phenotypic plasticity within and between generations across a range of traits to accurately predict how organisms will respond to climate change
Inverse Association between Dietary Iron Intake and Gastric Cancer: A Pooled Analysis of CaseâControl Studies of the Stop Consortium
Background: Inconsistent findings have been reported regarding the relationship between dietary iron intake and the risk of gastric cancer (GC). Methods: We pooled data from 11 caseâcontrol studies from the Stomach Cancer Pooling (StoP) Project. Total dietary iron intake was derived from food frequency questionnaires combined with national nutritional tables. We derived the odds ratios (ORs) and 95% confidence intervals (CIs) for quartiles of dietary iron through multivariable unconditional logistic regression models. Secondary analyses stratified by sex, smoking status, caloric intake, anatomical subsite and histological type were performed. Results: Among 4658 cases and 12247 controls, dietary iron intake was inversely associated with GC (per quartile OR 0.88; 95% CI: 0.83â0.93). Results were similar between cardia (OR = 0.85, 95% CI = 0.77â0.94) and nonâcardia GC (OR = 0.87, 95% CI = 0.81â0.94), and for diffuse (OR = 0.79, 95% CI = 0.69â0.89) and intestinal type (OR = 0.88, 95% CI = 0.79â0.98). Iron intake exerted an independent effect from that of smoking and salt intake. Additional adjustment by meat and fruit/vegetable intake did not alter the results. Conclusions: Dietary iron is inversely related to GC, with no difference by subsite or histological type. While the results should be interpreted with caution, they provide evidence against a direct effect of iron in gastric carcinogenesis
Inverse Association between Dietary Iron Intake and Gastric Cancer: A Pooled Analysis of CaseâControl Studies of the Stop Consortium
Background: Inconsistent findings have been reported regarding the relationship between dietary iron intake and the risk of gastric cancer (GC). Methods: We pooled data from 11 caseâcontrol studies from the Stomach Cancer Pooling (StoP) Project. Total dietary iron intake was derived from food frequency questionnaires combined with national nutritional tables. We derived the odds ratios (ORs) and 95% confidence intervals (CIs) for quartiles of dietary iron through multivariable unconditional logistic regression models. Secondary analyses stratified by sex, smoking status, caloric intake, anatomical subsite and histological type were performed. Results: Among 4658 cases and 12247 controls, dietary iron intake was inversely associated with GC (per quartile OR 0.88; 95% CI: 0.83â0.93). Results were similar between cardia (OR = 0.85, 95% CI = 0.77â0.94) and nonâcardia GC (OR = 0.87, 95% CI = 0.81â0.94), and for diffuse (OR = 0.79, 95% CI = 0.69â0.89) and intestinal type (OR = 0.88, 95% CI = 0.79â0.98). Iron intake exerted an independent effect from that of smoking and salt intake. Additional adjustment by meat and fruit/vegetable intake did not alter the results. Conclusions: Dietary iron is inversely related to GC, with no difference by subsite or histological type. While the results should be interpreted with caution, they provide evidence against a direct effect of iron in gastric carcinogenesis. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.This study was supported by the Fondazione AIRC per la Ricerca sul Cancro, Project no. 21378 (Investigator Grant). The Unidade de Investigação em EpidemiologiaâInstituto de SaĂșde PĂșblica da Universidade do Porto (EPIUnit; UIDB/04750/2020) and the LaboratĂłrio para a Investigação Integrativa e Translacional em SaĂșde Populacional (ITR; LA/P/0064/2020) were funded by the Foundation for Science and TechnologyâFCT (Portuguese Ministry of Science, Technology and Higher Education). SM was supported by the project âNEONâPCâNeuroâoncological complications of prostate cancer: longitudinal study of cognitive declineâ (POCIâ01â0145âFEDERâ032358; ref. PTDC/SAUâEPI/32358/2017), which is funded by FEDER through the Operational Programme competitiveness and Internationalization, and national funding from FCT and the EPIUnitâJunior ResearchâProg Financing (UIDP/04750/2020). The authors thank the European Cancer Prevention (ECP) Organization for providing support for the StoP Project meetings and all MCCâSpain study collaborators (CIBERESP, ISCIII, ISGlobal, ICO, University of Huelva, University of Oviedo, University of Cantabria, ibs.Granada, Instituto Salud PĂșblica de Navarra, FISABIO, Murcia Regional Health Authority and cols)
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