RESUMO
OBJECTIVES: This study tests, for the first time, the applicability of a new method of sex estimation utilizing enamel peptides on a sample of deciduous and permanent teeth at different stages of mineralization, from nonadults of unknown sex, including perinates. MATERIALS AND METHODS: A total of 43 teeth from 29 nonadult individuals aged from 40 gestational weeks to 19 years old were analyzed. The sample included pairs of fully mineralized and just developing teeth from the same individual. The individuals were from four archaeological sites in England: Piddington (1st-2nd centuries AD), Coach Lane, Victoria Gate, and Fewston (all 18th-19th centuries). A method that identifies sex chromosome-linked isoforms of the peptide amelogenin from human tooth enamel was applied. The method utilizes a minimally destructive acid etching procedure and subsequent nano liquid chromatography tandem mass spectrometry. RESULTS: It was possible to determine the sex of 28 of the nonadult individuals sampled (males = 20, females = 8, undetermined = 1). Only one sample failed (CL9), due to insufficient mineralization of the sampled tooth enamel. Data are available via ProteomeXchange with identifier PXD021683. DISCUSSION: Sufficient peptide material to determine sex can be recovered even from the crowns of developing perinatal teeth that are not fully mineralized. The minimally destructive and inexpensive (compared to ancient DNA) nature of this procedure has significant implications for bioarchaeological studies of infancy and childhood.
Assuntos
Amelogenina/análise , Análise para Determinação do Sexo/métodos , Dente/química , Dente/crescimento & desenvolvimento , Adolescente , Adulto , Amelogenina/química , Arqueologia , Sepultamento/história , Criança , Pré-Escolar , Esmalte Dentário/química , Esmalte Dentário/crescimento & desenvolvimento , Inglaterra , Feminino , História do Século XVIII , História do Século XIX , Humanos , Lactente , Recém-Nascido , Masculino , Espectrometria de Massas , Adulto JovemRESUMO
The tumor microenvironment is a determinant of cancer progression and therapeutic efficacy, with nutrient availability playing an important role. Although it is established that the local abundance of specific nutrients defines the metabolic parameters for tumor growth, the factors guiding nutrient availability in tumor compared to normal tissue and blood remain poorly understood. To define these factors in renal cell carcinoma (RCC), we performed quantitative metabolomic and comprehensive lipidomic analyses of tumor interstitial fluid (TIF), adjacent normal kidney interstitial fluid (KIF), and plasma samples collected from patients. TIF nutrient composition closely resembles KIF, suggesting that tissue-specific factors unrelated to the presence of cancer exert a stronger influence on nutrient levels than tumor-driven alterations. Notably, select metabolite changes consistent with known features of RCC metabolism are found in RCC TIF, while glucose levels in TIF are not depleted to levels that are lower than those found in KIF. These findings inform tissue nutrient dynamics in RCC, highlighting a dominant role of non-cancer driven tissue factors in shaping nutrient availability in these tumors.
RESUMO
The tumor microenvironment is a determinant of cancer progression and therapeutic efficacy, with nutrient availability playing an important role. Although it is established that the local abundance of specific nutrients defines the metabolic parameters for tumor growth, the factors guiding nutrient availability in tumor compared to normal tissue and blood remain poorly understood. To define these factors in renal cell carcinoma (RCC), we performed quantitative metabolomic and comprehensive lipidomic analyses of tumor interstitial fluid (TIF), adjacent normal kidney interstitial fluid (KIF), and plasma samples collected from patients. TIF nutrient composition closely resembles KIF, suggesting that tissue-specific factors unrelated to the presence of cancer exert a stronger influence on nutrient levels than tumor-driven alterations. Notably, select metabolite changes consistent with known features of RCC metabolism are found in RCC TIF, while glucose levels in TIF are not depleted to levels that are lower than those found in KIF. These findings inform tissue nutrient dynamics in RCC, highlighting a dominant role of non-cancer-driven tissue factors in shaping nutrient availability in these tumors.
Cancer cells convert nutrients into energy differently compared to healthy cells. This difference in metabolism allows them to grow and divide more quickly and sometimes to migrate to different areas of the body. The environment around cancer cells known as the tumor microenvironment contains a variety of different cells and blood vessels, which are bathed in interstitial fluid. This microenvironment provides nutrients for the cancer cells to metabolize, and therefore influences how well a tumor grows and how it might respond to treatment. Recent advances with techniques such as mass spectrometry, which can measure the chemical composition of a substance, have allowed scientists to measure nutrient levels in the tumor microenvironments of mice. However, it has been more difficult to conduct such studies in humans, as well as to compare the tumor microenvironment to the healthy tissue the tumors arose from. Abbott, Ali, Reinfeld et al. aimed to fill this gap in knowledge by using mass spectrometry to measure the nutrient levels in the tumor microenvironment of 55 patients undergoing surgery to remove kidney tumors. Comparing the type and levels of nutrients in the tumor interstitial fluid, the neighboring healthy kidney and the blood showed that nutrients in the tumor and healthy kidney were more similar to each other than those in the blood. For example, both the tumor and healthy kidney interstitial fluids contained less glucose than the blood. However, the difference between nutrient composition in the tumor and healthy kidney interstitial fluids was insignificant, suggesting that the healthy kidney and its tumor share a similar environment. Taken together, the findings indicate that kidney cancer cells must adapt to the nutrients available in the kidney, rather than changing what nutrients are available in the tissue. Future studies will be required to investigate whether this finding also applies to other types of cancer. A better understanding of how cancer cells adapt to their environments may aid the development of drugs that aim to disrupt the metabolism of tumors.