The chaperone system in glioblastoma multiforme and derived cell lines: diagnostic and mechanistic implications

BACKGROUND: Glioblastoma multiforme (GBM) is the most common and malignant primary brain tumor in adults. Novel treatments are needed to counteract the molecular mechanisms of GBM growth and drug resistance. The chaperone system (CS) members are typically cytoprotective but some, termed Hsp, can become pathogenic and participate in carcinogenesis, along with the vascular endothelial growth factor (VEGF), and we investigated them in GBM biopsies and derived cell lines. The objectives were to identify diagnostic-prognostic biomarkers and gather information for developing chaperonotherapy. METHODS: Cell lines from GBMs were established, characterized (morphology, growth characteristics, and specific markers), and stored. Chaperones and angiogenic factors [Hsp10, Hsp27, Hsp60, Hsp70, Hsp90, FLT-1 (VEGFR-1), FLK1 (KDR, VEGFR-2), and FLT-4 (VEGFR-3)] were observed in cells by immunofluorescence while the chaperones were measured in tumor tissue by immunohistochemistry. RESULTS: Four cell lines were derived from four different GBMs; the cells were spindle shaped or polygonal and grew at high rates as adherent monolayers or clusters without evidence of contact inhibition. The astrocyte-specific glial fibrillary acidic protein (GFAP); and the neuronal NSE, malignancy VIM, and proliferation PCNA, markers were determined. The cells expressed GFAP but no NSE, indicating that they were primary glioblastoma cell lines, with high levels of Hsp10, Hsp27, Hsp60, Hsp90, and Flk1; and low levels of Hsp70, Flt1, and Flt4. CONCLUSIONS: Four cell lines were established derived from four out of ten GBM tumors studied. The cell lines showed intense positivity for chaperones studied and factors connected to malignancy and the tumors showed increased levels of chaperones, making them potential diagnostic-prognostic biomarkers and targets for anti-cancer compounds

The triad hsp60-mirnas-extracellular vesicles in brain tumors: Assessing its components for understanding tumorigenesis and monitoring patients

Brain tumors have a poor prognosis and progress must be made for developing efficacious treatments, but for this to occur their biology and interaction with the host must be elucidated beyond current knowledge. What has been learned from other tumors may be applied to study brain tumors, for example, the role of Hsp60, miRNAs, and extracellular vesicles (EVs) in the mechanisms of cell proliferation and dissemination, and resistance to immune attack and anticancer drugs. It has been established that Hsp60 increases in cancer cells, in which it occurs not only in the mitochondria but also in the cytosol and plasma-cell membrane and it is released in EVs into the extracellular space and in circulation. There is evidence suggesting that these EVs interact with cells near and far from their original cell and that this interaction has an impact on the functions of the target cell. It is assumed that this crosstalk between cancer and host cells favors carcinogenesis in various ways. We, therefore, propose to study the triad Hsp60-related miRNAs-EVs in brain tumors and have standardized methods for the purpose. These revealed that EVs with Hsp60 and related miRNAs increase in patients’ blood in a manner that reflects disease status. The means are now available to monitor brain tumor patients by measuring the triad and to dissect its effects on target cells in vitro, and in experimental models in vivo

Factors Affecting Infestation by Triatoma infestans in a Rural Area of the Humid Chaco in Argentina: A Multi-Model Inference Approach

Vector-borne transmission of Chagas disease remains a major public health problem in parts of Latin America. Triatoma infestans is the main vector in the countries located in the South American Cone, particularly in the Gran Chaco ecoregion where residual insecticide control has achieved only a moderate, irregular impact. To contribute to improved control strategies, we analyzed the factors associated with the presence and abundance of T. infestans in 327 inhabited houses in a well-defined rural area with no recent vector control interventions in the humid Argentine Chaco. Bugs were found mainly in domiciles, kitchens, storerooms, and chicken coops and nests, particularly where adequate refuge and animal hosts (humans, dogs, cats or poultry) were available. Domiciles constructed from mud were the most often infested, but brick-and-cement domiciles, even in good conditions, were also found infested. Availability of refuge and hosts for T. infestans are key targets for vector control. Ten-fold variations in domestic infestation observed across neighboring villages, and differences in the relevant factors for T. infestans presence with respect to other areas of the Gran Chaco region suggest that host management, building techniques and insecticide use need to be tailored to the local environment, socio-economic characteristics, and climatic conditions

The Protracted Holocene Extinction of California\u27s Flightless Sea Duck (\u3cem\u3eChendytes lawi\u3c/em\u3e) and its Implications for the Pleistocene Overkill Hypothesis

Bones of the flightless sea duck (Chendytes lawi) from 14 archaeological sites along the California coast indicate that humans hunted the species for at least 8,000 years before it was driven to extinction. Direct 14C dates on Chendytes bones show that the duck was exploited on the southern California islands as early as ≈ 11,150-10,280 calendar years B.P., and on the mainland by at least 8,500 calendar years B.P. The youngest direct date of 2,720-2,350 calendar years B.P., combined with the absence of Chendytes bones from hundreds of late Holocene sites, suggests that the species was extinct by ≈2,400 years ago. Although the extinction of Chendytes clearly resulted from human overhunting, its demise raises questions about the Pleistocene overkill model, which suggests that megafauna were driven to extinction in a blitzkrieg fashion by Native Americans ≈13,000 years ago. That the extermination of Chendytes was so protracted and archaeologically visible suggests that, if the terminal Pleistocene megafauna extinctions were primarily the result of human exploitation, there should also be a long and readily detectable archaeological record of their demise. The brief window now attributed to the Clovis culture (≈13,300-12,900 B.P.) seems inconsistent with an overhunting event

Prehistoric Marine Mammal Overkill in the Northeastern Pacific: A Review of New Evidence

A model of prehistoric marine mammal overexploitation advanced by Hildebrandt and Jones (1992) for the northeastern Pacific has been challenged by Colten (1995) and Colten and Arnold (1998) who argue that diachronic patterns in faunal remains from California's Channel Islands reflect climatically-induced decline in marine productivity and local socio-cultural developments not overpredation. In this paper, we point out that some Channel Islands faunal trends are consistent with overexploitation, while others reflect methodological variation between studies. Newly available paleoenvironmental data raise questions about previous characterizations of late Holocene marine productivity, while new zooarchaeological findings from Monterey Bay, San Miguel and San Clemente Islands provide strong support for overexploitation in ways not envisioned in the original model. Such findings show that linear optimal foraging constructs may not account for all local variation in faunal assemblages, but still provide powerful explanations for broad patterns over time and can further provide useful insights into prehistoric human ecology

Prehistoric Marine Mammal Overkill in the Northeastern Pacific: A Review of New Evidence

A model of prehistoric marine mammal overexploitation advanced by Hildebrandt and Jones (1992) for the northeastern Pacific has been challenged by Colten (1995) and Colten and Arnold (1998) who argue that diachronic patterns in faunal remains from California’s Channel Islands reflect climatically-induced decline in marine productivity and local socio-cultural developments not over predation. In this paper, we point out that some Channel Islands faunal trends are consistent with overexploitation, while others reflect methodological variation between studies. Newly available paleoenvironmental data raise questions about previous characterizations of late Holocene marine productivity, while new zooarchaeological findings from Monterey Bay, San Miguel and San Clemente Islands provide strong support for overexploitation in ways not envisioned in the original model. Such findings show that linear optimal foraging constructs may not account for all local variation in faunal assemblages, but still provide powerful explanations for broad patterns over time and can further provide useful insights into prehistoric human ecology

The protracted Holocene extinction of California's flightless sea duck (Chendytes lawi) and its implications for the Pleistocene overkill hypothesis

Bones of the flightless sea duck (Chendytes lawi) from 14 archaeological sites along the California coast indicate that humans hunted the species for at least 8,000 years before it was driven to extinction. Direct 14C dates on Chendytes bones show that the duck was exploited on the southern California islands as early as ≈11,150–10,280 calendar years B.P., and on the mainland by at least 8,500 calendar years B.P. The youngest direct date of 2,720–2,350 calendar years B.P., combined with the absence of Chendytes bones from hundreds of late Holocene sites, suggests that the species was extinct by ≈2,400 years ago. Although the extinction of Chendytes clearly resulted from human overhunting, its demise raises questions about the Pleistocene overkill model, which suggests that megafauna were driven to extinction in a blitzkrieg fashion by Native Americans ≈13,000 years ago. That the extermination of Chendytes was so protracted and archaeologically visible suggests that, if the terminal Pleistocene megafauna extinctions were primarily the result of human exploitation, there should also be a long and readily detectable archaeological record of their demise. The brief window now attributed to the Clovis culture (≈13,300–12,900 B.P.) seems inconsistent with an overhunting event