RESUMO
PURPOSE: A previous real-world study conducted in China confirmed that first-line atezolizumab, in combination with etoposide/platinum (EP), leads to significantly longer progression-free survival (PFS) compared to EP alone in patients with extensive-stage small-cell lung cancer (ES-SCLC). The present study aimed to provide updated survival outcome data and evaluate the clinical efficacy of atezolizumab plus chemotherapy in ES-SCLC patients with brain metastasis (BM). METHODS: This retrospective study included 225 patients with ES-SCLC who were treated with EP alone (EP group) or a combination of EP + atezolizumab (atezolizumab group). Survival outcomes for the total study sample and patients in the BM subgroup were estimated using the Kaplan-Meier method. RESULTS: The atezolizumab group continued to demonstrate significantly longer PFS than the EP group (hazard ratio [HR], 0.68). The median overall survival (OS) was 26.2 months in the atezolizumab group vs. 14.8 months in the EP group (HR, 0.63). Additionally, among the BM patients in our study, the median PFS was found to be longer in the atezolizumab group (7.0 months) than in the EP group (4.1 months) (HR, 0.46). The OS of the BM patients did not differ significantly between the two treatment groups. CONCLUSIONS: The addition of atezolizumab to EP as a first-line treatment for ES-SCLC was found to improve survival outcomes. This treatment combination may also prolong PFS in patients with BM, regardless of the administration of cranial irradiation. However, among the BM patients in our study, there was no significant difference in OS between the two treatment groups.
Assuntos
Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Encefálicas , Etoposídeo , Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Masculino , Etoposídeo/administração & dosagem , Etoposídeo/uso terapêutico , Estudos Retrospectivos , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/patologia , Carcinoma de Pequenas Células do Pulmão/mortalidade , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/mortalidade , Feminino , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Pessoa de Meia-Idade , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/mortalidade , Idoso , Adulto , Intervalo Livre de Progressão , Estimativa de Kaplan-Meier , Cisplatino/administração & dosagem , Cisplatino/uso terapêutico , Taxa de Sobrevida , Idoso de 80 Anos ou maisRESUMO
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
RESUMO
There are substantive problems associated with invasive species, including threats to endemic organisms and biodiversity. Understanding the mechanisms driving invasions is thus critical. Variable extended phenotypes may enable animals to invade into novel environments. We explored here the proposition that silk variability is a facilitator of invasive success for the highly invasive Australian house spider, Badumna longinqua. We compared the physico-chemical and mechanical properties and underlying gene expressions of its major ampullate (MA) silk between a native Sydney population and an invasive counterpart from Montevideo, Uruguay. We found that while differential gene expressions might explain the differences in silk amino acid compositions and protein nanostructures, we did not find any significant differences in silk mechanical properties across the populations. Our results accordingly suggest that B. longinqua's silk remains functionally robust despite underlying physico-chemical and genetic variability as the spider expands its range across continents. They also imply that a combination of silk physico-chemical plasticity combined with mechanical robustness might contribute more broadly to spider invasibilities.
Assuntos
Espécies Introduzidas , Seda/química , Aranhas/química , Resistência à Tração , Animais , Fenômenos Biomecânicos , Especificidade da Espécie , Propriedades de SuperfícieRESUMO
Although phylogenetic studies have shown covariation between the properties of spider major ampullate (MA) silk and web building, both spider webs and silks are highly plastic so we cannot be sure whether these traits functionally covary or just vary across environments that the spiders occupy. As MaSp2-like proteins provide MA silk with greater extensibility, their presence is considered necessary for spider webs to effectively capture prey. Wolf spiders (Lycosidae) are predominantly non-web building, but a select few species build webs. We accordingly collected MA silk from two web-building and six non-web-building species found in semirural ecosystems in Uruguay to test whether the presence of MaSp2-like proteins (indicated by amino acid composition, silk mechanical properties and silk nanostructures) was associated with web building across the group. The web-building and non-web-building species were from disparate subfamilies so we estimated a genetic phylogeny to perform appropriate comparisons. For all of the properties measured, we found differences between web-building and non-web-building species. A phylogenetic regression model confirmed that web building and not phylogenetic inertia influences silk properties. Our study definitively showed an ecological influence over spider silk properties. We expect that the presence of the MaSp2-like proteins and the subsequent nanostructures improves the mechanical performance of silks within the webs. Our study furthers our understanding of spider web and silk co-evolution and the ecological implications of spider silk properties.
Assuntos
Seda , Especificidade da Espécie , Aranhas/genética , Aranhas/fisiologia , Animais , Ecossistema , Filogenia , Comportamento PredatórioRESUMO
Neonicotinoids are one of the world's most extensively used insecticides, but their sub-lethal influences on non-target and beneficial organisms are not well known. Here we exposed the orb web spider Parawixia audax, which is found on arable lands in Uruguay, to a sub-lethal concentration of the broad spectrum insecticide Geonex (thiamethoxam + lambda-cyhalothrin) and monitored their web building. We collected their major ampullate silk and subjected it to tensile tests, wide-angle X-ray diffraction (WAXS) analysis, and amino acid composition analysis. Around half of the exposed spiders failed to build webs. Those that built webs produced irregular webs lacking spiral threads. The mechanical properties, nanostructures, and amino acid compositions of the silk were all significantly affected when the spiders were exposed to insecticides. We found that silk proline, glutamine, alanine and glycine compositions differed between treatments, indicating that insecticide exposure induced downregulation of the silk protein MaSp2. The spiders in the control group had stronger, tougher and more extensible silks than those in the insecticide exposed group. Our WAXS analyses showed the amorphous region nanostructures became misaligned in insecticide exposed silks, explaining their greater stiffness. While the insecticide dose we subjected P. audax to was evidently sub-lethal, the changes in silk physicochemical properties and the impairment to web building will indelibly affect their ability to catch prey.