302 resultados para invasiveness
Resumo:
Spindle cell oncocytoma (SCO) is a recently described, rare neoplasm of the anterior pituitary. Clinically and radiologically simulating a non-functioning macroadenoma, its eponymous fusiform cells display a non-epithelial phenotype with conspicuous cytoplasmic accumulation of mitochondria. We report a case of SCO retrospectively identified in a biopsy specimen 16 years after transsphenoidal operation of a 48-year-old woman. Presenting symptoms were adynamia and transient decrease of visual acuity. Neuroimaging showed an isointense, enhancing, sellar-centered mass 1.8 cm in diameter without evidence of invasive growth. No postoperative adjuvant therapy was administered. The patient was left with panhypopituitarism, yet no recurrence was seen during follow-up. Initially diagnosed as a null cell adenoma of oncocytic type, repeat immunohistochemistry showed the characteristic coexpression of S100 protein, vimentin, and epithelial membrane antigen. Oncocytic granula stained intensely with antimitochondrial antibody 113-1, and were negative with the lysosomal marker CD68. Anterior pituitary hormones tested negative, and there was no evidence of neuroendocrine differentiation using antibodies to synaptophysin and chromogranin. Few cells stained for glial fibrillary acidic protein (GFAP). SCO has been proposed to represent a neoplasm of folliculo-stellate cells (FSCs). While the dynamic properties of the latter are incompletely characterized, and indeed no specific marker allows for their identification, overlapping features of SCO with look alikes, in particular pituicytoma, point to FSCs being a potential adult stem cell. The favorable outcome of the present case further argues for SCO to be considered a low-grade neoplasm. Moderate tumor size, lack of invasiveness, and low proliferation rate are likely predictors of benign behavior.
Resumo:
Image-guided, computer-assisted neurosurgery has emerged to improve localization and targeting, to provide a better anatomic definition of the surgical field, and to decrease invasiveness. Usually, in image-guided surgery, a computer displays the surgical field in a CT/MR environment, using axial, coronal or sagittal views, or even a 3D representation of the patient. Such a system forces the surgeon to look away from the surgical scene to the computer screen. Moreover, this kind of information, being pre-operative imaging, can not be modified during the operation, so it remains valid for guidance in the first stage of the surgical procedure, and mainly for rigid structures like bones. In order to solve the two constraints mentioned before, we are developing an ultrasoundguided surgical microscope. Such a system takes the advantage that surgical microscopy and ultrasound systems are already used in neurosurgery, so it does not add more complexity to the surgical procedure. We have integrated an optical tracking device in the microscope and an augmented reality overlay system with which we avoid the need to look away from the scene, providing correctly aligned surgical images with sub-millimeter accuracy. In addition to the standard CT and 3D views, we are able to track an ultrasound probe, and using a previous calibration and registration of the imaging, the image obtained is correctly projected to the overlay system, so the surgeon can always localize the target and verify the effects of the intervention. Several tests of the system have been already performed to evaluate the accuracy, and clinical experiments are currently in progress in order to validate the clinical usefulness of the system.
Resumo:
The prevention of ischaemia and the adequate restitution of blood flow to ischaemic tissue are pivotal to halt the progression of cellular injury associated with decreased oxygen and nutrient supply. Accordingly, the search for novel strategies which aim at preventing ischaemia-reperfusion-induced tissue damage is still of major interest in flap surgery. Preconditioning represents an elegant approach to render the tissue more resistant against deleterious ischaemic insults. For many decades, 'surgical delay' has been the standard method of tissue preconditioning. During the last 10 years, ischaemic preconditioning was added to the repertoire of plastic surgeons to protect flaps from ischaemic necrosis. The invasiveness and expenditure of time of these procedures, however, have always been major drawbacks, hindering a wide distribution in clinical practice. Consequently, the motivation has all along been to further refine and simplify protective strategies. Recent experimental studies have now shown that efficient protection from ischaemic necrosis can also be achieved by remote preconditioning or pretreatment with chemical agents and growth factors, which mimic the action of surgical delay and ischaemic preconditioning. In addition, the local application of unspecific stressors, including both heating and cooling, have been shown to effectively improve flap microcirculation and, thus, tissue survival. In view of successful translational research, it is now time that the efficacy of these novel preconditioning procedures is proven in prospective randomised clinical trials.
Resumo:
Epidermal growth factor (EGF) is excreted in a high concentration in human saliva and modulates the growth and differentiation of various cancer cells. To elucidate the molecular mechanisms by which EGF affects oral cancer growth and invasion, we analyzed the Matrigel invasion activity of the cultured oral cancer cell line. Cells grown under the influence of EGF were subjected to Matrigel invasion assays and cells grown in the absence of EGF were used as controls. Gelatin-zymography and Northern blot analyses quantified the invasiveness and tumorigenicity. Chloramphenicol acetyltransferase assay (CAT assay) determined the EGF stimulation of matrix metalloproteinase (MMP) expression. EGF increased the number of cells penetrating a Matrigel membrane. Gelatin-zymography and Northern blot analysis revealed that MMP9 and Ets1 expressions correlated with EGF but MMP2 was not changed. a transient transfection assay revealed that EGF increased the promoter activities of the MMP9 genes in HSC3 and SAS cells. These results suggest that EGF increases the invasion activity of oral cancer cells partly by increasing MMP9.
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Cathepsin D (Cath-D) expression in human primary breast cancer has been associated with a poor prognosis. In search of a better understanding of the Cath-D substrates possibly involved in cancer invasiveness and metastasis, we investigated the potential interactions between this protease and chemokines. Here we report that purified Cath-D, as well as culture supernatants from the human breast carcinoma cell lines MCF-7 and T47D, selectively degrade macrophage inflammatory protein (MIP)-1 alpha (CCL3), MIP-1 beta (CCL4), and SLC (CCL21). Proteolysis was totally blocked by the protease inhibitor pepstatin A, and specificity of Cath-D cleavage was demonstrated using a large chemokine panel. Whereas MIP-1 alpha and MIP-1 beta degradation was rapid and complete, cleavage of SLC was slow and not complete. Mass spectrometry analysis showed that Cath-D cleaves the Leu(58) to Trp(59) bond of SLC producing two functionally inactive fragments. Analysis of Cath-D proteolysis of a series of monocyte chemoattractant protein-3/MIP-1 beta hybrids indicated that processing of MIP-1 beta might start by cleaving off amino acids located in the C-terminal domain. In situ hybridization studies revealed MIP-1 alpha, MIP-1 beta, and Cath-D gene expression mainly in the stromal compartment of breast cancers whereas SLC transcripts were found in endothelial cells of capillaries and venules within the neoplastic tissues. Cath-D production in the breast carcinoma cell lines MCF-7 and T47D, as assessed by enzyme-linked immunosorbent assay of culture supernatants and cell lysates, was not affected by stimulation with chemokines such as interleukin-8 (CXCL8), SDF-1 (CXCL12), and SLC. These data suggest that inactivation of chemokines by Cath-D possibly influences regulatory mechanisms in the tumoral extracellular microenvironment that in turn may affect the generation of the antitumoral immune response, the migration of cancer cells, or both processes.
Resumo:
1. Plants interact with many organisms, such as microbes and herbivores, and these interactions are likely to affect the establishment and spread of plants. In the context of plant invasions, mycorrhizal fungi and constitutive and induced resistance of plants against herbivores have received attention independently of each other. However, plants are frequently involved in complex multi-trophic interactions, which might differ between invasive and non-invasive alien plants. 2. In a multi-species comparative experiment, we aimed to improve our understanding of plant traits associated with invasiveness. We tested whether eight invasive alien plant species use the mycorrhizal symbiosis in a more beneficial way, and have higher levels of constitutive or induced resistance against two generalist bioassay herbivores, than nine non-invasive alien species. We further assessed whether the presence of mycorrhizal fungi altered the resistance of the plant species, and whether this differed between invasive and non-invasive alien species. 3. While invasive species produced more biomass, they did not differ in their biomass response to mycorrhizal fungi from non-invasive alien species. Invasive species also did not have higher levels of constitutive or induced resistance against the two generalist herbivores. Mycorrhizal fungi greatly affected the resistance of our plant species, however, this was also unrelated to whether the alien species were invasive or not. 4. Our study confirms the previous findings that invasive species generally grow faster and produce more biomass than non-invasive alien species. We further show that alien plant species used a variety of defence strategies, and also varied in their interactions with mycorrhizal fungi. These multi-trophic interactions were not consistently related to invasiveness of the alien plant species. 5. We suggest that awareness of the fact that alien plant species are involved in multi-trophic interactions might lead to a more complete understanding of the factors contributing to a plant's success.
Resumo:
1 .In their colonized ranges, exotic plants may be released from some of the herbivores or pathogens of their home ranges but these can be replaced by novel enemies. It is of basic and practical interest to understand which characteristics of invaded communities control accumulation of the new pests. Key questions are whether enemy load on exotic species is smaller than on native competitors as suggested by the enemy release hypothesis (ERH) and whether this difference is most pronounced in resource-rich habitats as predicted by the resource–enemy release hypothesis (R-ERH). 2. In 72 populations of 12 exotic invasive species, we scored all visible above-ground damage morphotypes caused by herbivores and fungal pathogens. In addition, we quantified levels of leaf herbivory and fruit damage. We then assessed whether variation in damage diversity and levels was explained by habitat fertility, by relatedness between exotic species and the native community or rather by native species diversity. 3. In a second part of the study, we also tested the ERH and the R-ERH by comparing damage of plants in 28 pairs of co-occurring native and exotic populations, representing nine congeneric pairs of native and exotic species. 4. In the first part of the study, diversity of damage morphotypes and damage levels of exotic populations were greater in resource-rich habitats. Co-occurrence of closely related, native species in the community significantly increased the probability of fruit damage. Herbivory on exotics was less likely in communities with high phylogenetic diversity. 5. In the second part of the study, exotic and native congeneric populations incurred similar damage diversity and levels, irrespective of whether they co-occurred in nutrient-poor or nutrient-rich habitats. 9. Synthesis. We identified habitat productivity as a major community factor affecting accumulation of enemy damage by exotic populations. Similar damage levels in exotic and native congeneric populations, even in species pairs from fertile habitats, suggest that the enemy release hypothesis or the R-ERH cannot always explain the invasiveness of introduced species.
Resumo:
Aim: Accumulating evidence indicates that species may be pre-adapted for invasion success in new ranges. In the light of increasing global nutrient accumulation, an important candidate pre-adaptation for invasiveness is the ability to grow in nutrient-rich habitats. Therefore we tested whether globally invasive species originating from Central Europe have come from more productive rather than less productive habitats. A further important candidate pre-adaptation for invasiveness is large niche width. Therefore, we also tested whether species able to grow across habitats with a wider range of productivity are more invasive. Location: Global with respect to invasiveness, and Central European with respect to origin of study species. Methods We examined whether average habitat productivity and its width across habitats are significant predictors of the success of Central European species as aliens and as weeds elsewhere in the world based on data in the Global Compendium of Weeds. The two habitat productivity measures were derived from nutrient indicator values (after Ellenberg) of accompanying species present in vegetation records of the comprehensive Czech National Phytosociological Database. In the analyses, we accounted for phylogenetic relatedness among species and for size of the native distribution ranges. Results: Species from more productive habitats and with a wider native habitat-productivity niche in Central Europe have higher alien success elsewhere in the world. Weediness of species increased with mean habitat productivity. Niche width was also an important determinant of weediness for species with their main occurrence in nutrient-poor habitats, but not for those from nutrient-rich habitats. Main conclusions: Our results indicate that Central European plant species from productive habitats and those species from nutrient-poor habitat with wide productivity-niche are pre-adapted to become invasive. These results suggest that the world-wide invasion success of many Central European species is likely to have been promoted by the global increase of resource-rich habitats.
Resumo:
Clonality is frequently positively correlated with plant invasiveness, but which aspects of clonality make some clonal species more invasive than others is not known. Due to their spreading growth form, clonal plants are likely to experience spatial heterogeneity in nutrient availability. Plasticity in allocation of biomass to clonal growth organs and roots may allow these plants to forage for high-nutrient patches. We investigated whether this foraging response is stronger in species that have become invasive than in species that have not. We used six confamilial pairs of native European clonal plant species differing in invasion success in the USA. We grew all species in large pots under homogeneous or heterogeneous nutrient conditions in a greenhouse, and compared their nutrient-foraging response and performance. Neither invasive nor non-invasive species showed significant foraging responses to heterogeneity in clonal growth organ biomass or in aboveground biomass of clonal offspring. Invasive species had, however, a greater positive foraging response in terms of root and belowground biomass than non-invasive species. Invasive species also produced more total biomass. Our results suggest that the ability for strong root foraging is among the characteristics promoting invasiveness in clonal plants.
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The treatment of high-risk prostate cancer (HRPCa) is a tremendous challenge for uro-oncologists. The identification of predictive moleculobiological markers allowing risk assessment of lymph node metastasis and systemic progression is essential in establishing effective treatment. In the current study, we investigate the prognostic potential of miR-205 in HRPCa study and validation cohorts, setting defined clinical endpoints for both. We demonstrate miR-205 to be significantly down-regulated in over 70% of the HRPCa samples analysed and that reconstitution of miR-205 causes inhibition of proliferation and invasiveness in prostate cancer (PCa) cell lines. Additionally, miR-205 is increasingly down-regulated in lymph node metastases compared to the primary tumour indicating that miR-205 plays a role in migration of PCa cells from the original location into extraprostatic tissue. Nevertheless, down-regulation of miR-205 in primary PCa was not correlated to the synchronous presence of metastasis and failed to predict the outcome for HRPCa patients. Moreover, we found a tendency for miR-205 up-regulation to correlate with an adverse outcome of PCa patients suggesting a pivotal role of miR-205 in tumourigenesis. Overall, we showed that miR-205 is involved in the development and metastasis of PCa, but failed to work as a useful clinical biomarker in HRPCa. These findings might have implications for the use of miR-205 as a prognostic or therapeutic target in HRPCa.
Resumo:
AIMS Follicular thyroid carcinoma (FTC) has been a diagnostic challenge for decades. The PAX8-PPARγ rearrangement has been detected in FTC and classic papillary thyroid carcinomas (PTCs). The aims of this study were to assess the presence of PAX8-PPARγ by using tissue microarrays in a large cohort of different thyroid neoplasms, and to assess its diagnostic and prognostic implications. METHODS AND RESULTS Fluorescence in-situ hybridization (FISH) analysis for PAX8-PPARγ was performed on 226 thyroid tumours, comprising FTCs (n = 59), PTCs (n = 126), poorly differentiated thyroid carcinomas (PDs; n = 34), follicular thyroid adenomas (FTAs; n = 5), and follicular tumours of unknown malignant potential (FTUMPs; n = 2). PAX8-PPARγ was detected in 12% of FTCs, 1% of PTCs, 7% of PDs, and in both cases of FTUMP. There was no correlation between the extent of capsular or vascular invasion and PAX8-PPARγ, or between lymph node or haematogenous metastasis and PAX8-PPARγ. Overall survival (OS), tumour-specific survival (TSS) and relapse-free-survival (RFS) were not influenced by PAX8-PPARγ. CONCLUSIONS In this study, we demonstrate for the first time the presence of PAX8-PPARγ in PDs and FTUMPs, whereas in FTCs and PTCs the prevalence of PAX8-PPARγ is lower than previously reported. PAX8-PPARγ did not correlate with invasiveness or affect prognosis in any tumour type.
Resumo:
Despite major advances in the study of glioma, the quantitative links between intra-tumor molecular/cellular properties, clinically observable properties such as morphology, and critical tumor behaviors such as growth and invasiveness remain unclear, hampering more effective coupling of tumor physical characteristics with implications for prognosis and therapy. Although molecular biology, histopathology, and radiological imaging are employed in this endeavor, studies are severely challenged by the multitude of different physical scales involved in tumor growth, i.e., from molecular nanoscale to cell microscale and finally to tissue centimeter scale. Consequently, it is often difficult to determine the underlying dynamics across dimensions. New techniques are needed to tackle these issues. Here, we address this multi-scalar problem by employing a novel predictive three-dimensional mathematical and computational model based on first-principle equations (conservation laws of physics) that describe mathematically the diffusion of cell substrates and other processes determining tumor mass growth and invasion. The model uses conserved variables to represent known determinants of glioma behavior, e.g., cell density and oxygen concentration, as well as biological functional relationships and parameters linking phenomena at different scales whose specific forms and values are hypothesized and calculated based on in vitro and in vivo experiments and from histopathology of tissue specimens from human gliomas. This model enables correlation of glioma morphology to tumor growth by quantifying interdependence of tumor mass on the microenvironment (e.g., hypoxia, tissue disruption) and on the cellular phenotypes (e.g., mitosis and apoptosis rates, cell adhesion strength). Once functional relationships between variables and associated parameter values have been informed, e.g., from histopathology or intra-operative analysis, this model can be used for disease diagnosis/prognosis, hypothesis testing, and to guide surgery and therapy. In particular, this tool identifies and quantifies the effects of vascularization and other cell-scale glioma morphological characteristics as predictors of tumor-scale growth and invasion.
Resumo:
Pancreatic ductal adenocarcinoma (PDAC) ranks as the fourth commonest cause of cancer death while its incidence is increasing worldwide. For all stages, survival at 5 years is<5%. The lethal nature of pancreatic cancer is attributed to its high metastatic potential to the lymphatic system and distant organs. Lack of effective therapeutic options contributes to the high mortality rates of PDAC. Recent evidence suggests that epithelial-mesenchymal transition (EMT) plays an important role to the disease progression and development of drug resistance in PDAC. Tumor budding is thought to reflect the process of EMT which allows neoplastic epithelial cells to acquire a mesenchymal phenotype thus increasing their capacity for migration and invasion and help them become resistant to apoptotic signals. In a recent study by our own group the presence and prognostic significance of tumor budding in PDAC were investigated and an association between high-grade budding and aggressive clinicopathological features of the tumors as well as worse outcome of the patients was found. The identification of EMT phenotypic targets may help identifying new molecules so that future therapeutic strategies directed specifically against them could potentially have an impact on drug resistance and invasiveness and hence improve the prognosis of PDAC patients. The aim of this short review is to present an insight on the morphological and molecular aspects of EMT and on the factors that are involved in the induction of EMT in PDAC.
Resumo:
Despite major advances in the study of glioma, the quantitative links between intra-tumor molecular/cellular properties, clinically observable properties such as morphology, and critical tumor behaviors such as growth and invasiveness remain unclear, hampering more effective coupling of tumor physical characteristics with implications for prognosis and therapy. Although molecular biology, histopathology, and radiological imaging are employed in this endeavor, studies are severely challenged by the multitude of different physical scales involved in tumor growth, i.e., from molecular nanoscale to cell microscale and finally to tissue centimeter scale. Consequently, it is often difficult to determine the underlying dynamics across dimensions. New techniques are needed to tackle these issues. Here, we address this multi-scalar problem by employing a novel predictive three-dimensional mathematical and computational model based on first-principle equations (conservation laws of physics) that describe mathematically the diffusion of cell substrates and other processes determining tumor mass growth and invasion. The model uses conserved variables to represent known determinants of glioma behavior, e.g., cell density and oxygen concentration, as well as biological functional relationships and parameters linking phenomena at different scales whose specific forms and values are hypothesized and calculated based on in vitro and in vivo experiments and from histopathology of tissue specimens from human gliomas. This model enables correlation of glioma morphology to tumor growth by quantifying interdependence of tumor mass on the microenvironment (e.g., hypoxia, tissue disruption) and on the cellular phenotypes (e.g., mitosis and apoptosis rates, cell adhesion strength). Once functional relationships between variables and associated parameter values have been informed, e.g., from histopathology or intra-operative analysis, this model can be used for disease diagnosis/prognosis, hypothesis testing, and to guide surgery and therapy. In particular, this tool identifies and quantifies the effects of vascularization and other cell-scale glioma morphological characteristics as predictors of tumor-scale growth and invasion.
Resumo:
Empirical evidence and theoretical studies suggest that the phenotype, i.e., cellular- and molecular-scale dynamics, including proliferation rate and adhesiveness due to microenvironmental factors and gene expression that govern tumor growth and invasiveness, also determine gross tumor-scale morphology. It has been difficult to quantify the relative effect of these links on disease progression and prognosis using conventional clinical and experimental methods and observables. As a result, successful individualized treatment of highly malignant and invasive cancers, such as glioblastoma, via surgical resection and chemotherapy cannot be offered and outcomes are generally poor. What is needed is a deterministic, quantifiable method to enable understanding of the connections between phenotype and tumor morphology. Here, we critically assess advantages and disadvantages of recent computational modeling efforts (e.g., continuum, discrete, and cellular automata models) that have pursued this understanding. Based on this assessment, we review a multiscale, i.e., from the molecular to the gross tumor scale, mathematical and computational "first-principle" approach based on mass conservation and other physical laws, such as employed in reaction-diffusion systems. Model variables describe known characteristics of tumor behavior, and parameters and functional relationships across scales are informed from in vitro, in vivo and ex vivo biology. We review the feasibility of this methodology that, once coupled to tumor imaging and tumor biopsy or cell culture data, should enable prediction of tumor growth and therapy outcome through quantification of the relation between the underlying dynamics and morphological characteristics. In particular, morphologic stability analysis of this mathematical model reveals that tumor cell patterning at the tumor-host interface is regulated by cell proliferation, adhesion and other phenotypic characteristics: histopathology information of tumor boundary can be inputted to the mathematical model and used as a phenotype-diagnostic tool to predict collective and individual tumor cell invasion of surrounding tissue. This approach further provides a means to deterministically test effects of novel and hypothetical therapy strategies on tumor behavior.