Currently, novel mouse models of melanoma are being generated that recapitulate the histopathology and molecular pathogenesis observed in human disease. Impaired cell-cycle control, which is a hallmark of both familial and sporadic melanoma, promotes slowly growing carcinogen-induced melanomas in the skin of mice carrying a mutated cyclin-dependent kinase 4 (CDK4 R24C ). Deregulated receptor tyrosine kinase signaling, which is another important feature of human melanoma, leads to spontaneous development of metastatic melanoma after a long latency period in mice overexpressing hepatocyte growth factor/scatter factor (HGF/SF mice). Here we report that treatment with 7,12-dimethylbenz
Wastewater reuse contributes to closing the nutrient recycling loop as a sustainable way of managing water resources. Bangkok has over a thousand man-made drainage and irrigation canals for such purposes. Its use for agricultural and recreational purposes has a long tradition in rural and peri-urban areas. However, the continuation of these practices is increasingly questioned since potential health risks are an issue if such practices are not appropriately managed. The microbial and chemical quality of canal water has considerably deteriorated over the last decade, mainly because of discharged, untreated domestic and industrial wastewater. It is important to understand the health risks of wastewater reuse and identify risky behaviors from the most highly exposed actors promote the safe use of wastewater. This study assessed diarrhea infection risks caused by the use of and contact with wastewater in Klong Luang municipality, a peri-urban setting in Northern Bangkok, using quantitative microbial risk assessment. Wastewater samples were collected from canals, sewers at household level, and vegetables grown in the canals for consumption. Samples were also collected from irrigation water from the agricultural fields. Two protozoa, Giardia lamblia and Entamoeba histolytica, were quantified and analyzed by real-time PCR, exposure assessment was conducted, and finally, the risk of infection due to contact with wastewater in different scenarios was calculated. The results showed that canal water and vegetables were heavily contaminated with G. lamblia and E. histolytica. Infection risk was high in tested scenarios and largely exceeded the acceptable risk given by WHO guidelines.
Malignant melanoma is an attractive model disease for the development of antigen-specific immunotherapy because many antigens recognized by tumor-specific T cells have been identified. In C57BL/6 mice, genetic immunization with recombinant adenovirus encoding xenogeneic human tyrosinase-related protein 2 (Ad-hTRP2) induces protective but not therapeutic cellular immunity against growth of transplanted B16 melanoma cells. Here, we additionally applied CpG DNA and synthetic double-stranded RNA, which activate the innate immune system via Toll-like receptors (TLR). Both adenoviral vaccination and peritumoral injections of TLR ligands were required for rejection of established B16 melanoma in the skin. To more closely mimic the clinical situation in patients with melanoma, we evaluated this combined immunotherapeutic strategy in genetically modified mice, which overexpress hepatocyte growth factor (HGF) and carry an oncogenic mutation in the cyclin-dependent kinase 4 (CDK4) R24C . HGF Â CDK4 R24C mice rapidly develop multiple invasive melanomas in the skin following neonatal carcinogen treatment, which spontaneously metastasize to lymph nodes and lungs. Vaccination with Ad-hTRP2 followed by injections of TLR ligands resulted in delayed growth of autochthonous primary melanomas in the skin and reduction in the number of spontaneous lung metastases but did not induce tumor regression. Carcinogen-treated HGF Â CDK4 R24C mice bearing multiple autochthonous melanomas did not reject transplanted B16 melanoma despite treatment with Ad-hTRP2 and TLR ligands, suggesting the development of tumor immunotolerance. Further investigations in our novel genetic melanoma model may help to better understand the role of the immune system in the pathogenesis and treatment of this life-threatening disease.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.