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Assessing Prenatal and Neonatal Gonadal Steroid Exposure for Studies of Human Development: Methodological and Theoretical Challenges

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889196074 Year: Pages: 80 DOI: 10.3389/978-2-88919-607-4 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Internal medicine
Added to DOAB on : 2016-08-16 10:34:25
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There is extensive evidence from animal models that gonadal steroids, produced in fetal and neonatal life, act on the developing organism to produce sex differences far beyond the reproductive system. That early gonadal steroid exposure also plays an important role in human development is supported by studies of individuals with disorders of sex determination and differentiation. It is much less clear whether normal variation in gonadal steroid exposure predicts sexually dimorphic health outcomes or within-sex variation. This is largely due to challenges related to the assessment of gonadal steroid exposure in the developing fetus and neonate. Regarding the prenatal period, serial measurements of serum hormone levels in the fetus, for use in studies of later development, are not possible for ethical reasons. Researchers have measured hormones in maternal blood, umbilical cord blood, and amniotic fluid; used putative anthropometric indices such as the relative lengths of the 2nd and 4th digits (2D:4D); evaluated common variants in genes related to hormone production, transport, and metabolism; and examined development in opposite sex twins and the offspring of mothers with hyperandrogeny. Each of these approaches has particular strengths and notable weaknesses. Regarding the neonatal period, serial measurements in serum are often impractical for studies of typical development. Salivary hormone assays, frequently used in studies of older children and adults, have not been extensively investigated in neonates. The most appropriate timing for testing is also open to debate. Early work suggested that testosterone levels in males begin to rise after the first postnatal week, peak around the 3rd to 4th months of life, and then drop back to very low levels by 1 year. However a more recent study of 138 infants did not demonstrate this pattern. Testosterone was highest on the day of birth and gradually dropped over the first 6 months. Even less is known about patterns of early estrogen exposure, though highly sensitive bioassays indicated that sex differences are present in early childhood. In addition, the design and interpretation of studies may be impacted by widespread acceptance of conceptual frameworks that are not well-supported empirically. For example, many researchers presume that the free hormone hypothesis, which states that unbound hormone is more readily diffusible into tissues and thus a better measure of actual exposure, is true. However this hypothesis has been challenged on multiple grounds. A second example: it is generally accepted that masculinization of the human brain is primarily mediated by the androgen receptor (in contrast to rodents where the estrogen receptor plays a major role), in part because chromosomal males with complete androgen insensitivity generally espouse a female gender identity. However this is not always the case, and other sexually dimorphic outcomes have not been carefully assessed in CAIS. The aim of this research topic is to gather together experimental and review papers which address the diverse challenges in assessing prenatal and neonatal gonadal steroid exposure for studies of human development with the expectation that this will allow more critical appraisal of existing studies, identify critical research gaps, and improve the design of future studies.

Sex Hormone Receptor Signals in Human Malignancies

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ISBN: 9783039211739 9783039211746 Year: Pages: 152 DOI: 10.3390/books978-3-03921-174-6 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Science (General) --- Biology
Added to DOAB on : 2019-12-09 11:49:15
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Sex steroids, including androgens, estrogens, and progestogens, are knownto have widespread physiological actions beyond the reproductive systemvia binding to the sex hormone receptors. Meanwhile, emerging evidence hasindicated that sex hormone receptor signals are involved in the outgrowth ofsome malignancies, such as prostate and breast carcinomas, as well as othersthat have not traditionally been considered as endocrine-related neoplasms. ThisSpecial Issue “Sex Hormone Receptor Signals in Human Malignancies” coversvarious aspects of the potential role of sex hormone receptors and related signalsin prostate cancer, breast cancer, and other neoplastic conditions by depictingpromising findings derived from in vitro and in vivo experiments as well as theanalyses of surgical specimens. The current observations described may thusprovide a unique insight into novel or known functions of sex hormone receptorsand related molecules.

Advances in Peptide and Peptidomimetic Design Inspiring Basic Science and Drug Discovery: A Themed Issue Honoring Professor Victor J. Hruby on the Occasion of His 80th Birthday

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ISBN: 9783039282883 9783039282890 Year: Pages: 406 DOI: 10.3390/books978-3-03928-289-0 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Therapeutics --- Medicine (General)
Added to DOAB on : 2020-04-07 23:07:09
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Advances in Peptide and Peptidomimetic Design Inspiring Basic Science and Drug Discovery is a book dedicated to Prof. Victor J. Hruby on the occasion of his 80th birthday. This book includes twenty contributions from authors representing diverse multidisciplinary fields of scientific expertise, and is focused on the extraordinary potential of peptides and peptidomimetics as a surging therapeutic modality and as tools for basic research and technology development.

Keywords

MC3R --- MC4R --- mixed pharmacology --- tetrapeptides --- melanocortins --- Plk1 --- selectivity --- polo-box domain --- peptide --- triazole --- PKA --- stapled peptide --- PKI --- pseudosubstrate --- kinase inhibitor --- IP20 --- polycationic -amino acids --- small antimicrobial peptides --- sepsis --- peptidomimetics --- VEGF165 --- neuropilin-1 --- molecular dynamics --- structure–activity relationship --- OBOC --- combinatorial chemistry --- opioid --- drug screen --- molecular rotor dye --- high throughput screening --- sensor chip --- peptide --- peptide-drug conjugate --- mixed-mode pharmacology --- GLP-1 --- GnRH --- LHRH --- chemical linker --- cancer --- diabetes --- obesity --- drug discovery --- melanocortin-4 receptor --- obesity --- peptide agonist --- cardiovascular profile --- G?S signaling --- receptor desensitization --- receptor internalization --- peptidomimetics --- azapeptides --- aza-amino acids --- ?-hairpin --- ?-sheet --- programmed cell death ligand protein 1 --- pharmacophore --- peptide --- small molecule --- anticancer peptide --- therapeutic peptides --- support vector machine --- random forest --- machine learning --- classification --- peptides --- endosomolytic --- amphiphilic --- fusogenic --- influenza hemagglutinin --- RBC lysis --- peptide permeability --- stapled peptide --- macrocyclic peptide --- D-amino acid --- helix-breaker --- adaptogenic --- autophagy --- ?-ginkgotide --- cytoprotective --- cysteine-rich peptides --- disulfide-rich scaffold --- hyperdisulfide --- hypoxia --- LIR motif --- ginkgo nuts --- ?-helix mimetics --- bis-benzamide scaffold --- protein–protein interaction --- prostate cancer --- androgen receptor --- coactivator PELP1 --- Ranalexin --- peptide therapeutics --- antibiotics --- configuration --- antimicrobial activity --- cancer vaccine --- synthetic vaccine --- adjuvant --- Toll-like receptor --- Pam2Cys --- N-acetylated Pam2Cys --- bioconjugation --- lipidation --- prostaglandin F2? --- preterm labor --- myometrium contractions --- peptidomimetic --- structure-activity --- opioids --- multifunctional ligands --- peptide design --- free energy calculation --- d-amino acid scan --- alanine scan

Circulating Tumor Cells: Finding Rare Events for A Huge Knowledge of Cancer Dissemination

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ISBN: 9783039286980 / 9783039286997 Year: Pages: 366 DOI: 10.3390/books978-3-03928-699-7 Language: eng
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Medicine (General)
Added to DOAB on : 2020-06-09 16:38:57
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The analysis of circulating tumor cells (CTCs) as a real-time liquid biopsy approach can be used to obtain new insights into metastasis biology, and as companion diagnostics to improve the stratification of therapies and to obtain insights into the therapy-induced selection of cancer cells. In this book, we will cover all the different facets of CTCs to assemble a huge corpus of knowledge on cancer dissemination: technologies for their enrichment, detection, and characterization; their analysis at the single-cell level; their journey as CTC microemboli; their clinical relevance; their biology with the epithelial-to-mesenchymal transition (EMT); their stem-cell properties; their potential to initiate metastasis at distant sites; their ex vivo expansion; and their escape from the immune system.

Keywords

circulating tumor cells --- circulating tumor DNA --- liquid biopsy --- metastatic colorectal cancer --- FOLFIRINOX --- circulating tumor cells --- CTC --- liquid biopsy --- CTM --- CTMat --- CTC biology --- CTC capture technology --- metastasis --- circulating tumor cells (CTCs) --- hepatocellular carcinoma (HCC) --- castration resistant prostate cancer (CRPC) --- epithelial-to-mesenchymal transition (EMT) --- fibronectin --- integrin B1 --- SLUG --- major histocompatibility complex class I (MHCI) --- immunomodulation --- bone marrow --- melanoma --- disseminated tumor cells --- solid cancers --- single-cell analysis --- enrichment and detection technologies --- flow cytometry --- tumor stem cells --- HMB-45 --- CD133 --- locally advanced rectal cancer --- circulating tumor cells --- RAD23B --- thymidylate synthase --- chemoradioresistance --- liquid biopsy --- circulating tumor cells --- epithelial–mesenchymal transition --- stem cells --- early breast cancer --- prostate cancer (PCa) --- circulating tumor cells (CTC) --- liquid biopsy --- circulating tumor cells --- metastasis --- xenograft models --- breast cancer --- prostate cancer --- CTC --- AR --- AR-V7 --- ctRNA --- exosome --- circulating tumor cells --- hematological cells --- neutrophils --- platelets --- liquid biopsy --- circulating tumor cells --- melanoma --- liquid biopsy --- EPISPOT --- CellSearch® --- liquid biopsy --- CTCs --- immune checkpoint inhibitors --- PD-L1 expression --- NSCLC --- small-cell lung carcinoma --- circulating tumor cells --- microfluidics --- gene expression analysis --- synaptophysin --- chromogranin A --- rovalpituzumab tesirine --- leukocyte-derived extracellular vesicles --- immunofluorescence imaging --- EpCAM enrichment --- CellSearch --- EasyCount slides --- ACCEPT --- CTC --- heterogeneity --- liquid biopsy --- liquid surgery --- clinical utility --- circulating tumor cells (CTCs) --- glioma --- biomarker --- rVAR2 --- malaria --- enrichment and detection technologies --- prostate cancer --- biomarkers --- circulating tumor cells --- androgen receptor --- ARV7 --- abiraterone --- enzalutamide --- metastasis --- tumor-initiating cells (TICs) --- circulating tumor cells (CTCs) --- CTC-derived xenografts --- CTC-derived ex vivo models --- cerebrospinal liquid biopsy --- in vivo flow cytometry --- tumor biomarkers --- circulating tumor cells --- ctDNA --- miRNA --- exosomes --- emboli --- targeted therapy --- circulating tumor cells --- tumor cell dissemination --- immune system --- microbiome --- circulating tumor cells (CTCs) --- clinical trials --- breast cancer --- CTC-based treatment decisions --- circulating tumour cells --- colorectal cancer --- colorectal surgery --- microsatellite instability --- microfluidics --- immunophenotyping --- fish --- liquid biopsy --- circulating leukemia cells --- circulating plasma cells --- n/a

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