ABSTRACT
Triple negative breast cancer is considered as the worst aggressive subtype with poor prognosis. Recent studies suggest a hereditary component is involved in TNBC development, especially in young patients. However, genetic spectrum remains unclear. Our purpose was to evaluate the usefulness of multigene panel testing in triple negative patients compared to overall breast cancer cases as well as contributing to elucidate which genes are most implicated in triple negative subtype development. Two breast cancer cohorts, comprising 100 triple negative breast cancer patients and 100 patients with other breast cancer subtypes, were analyzed by Next-Generation Sequencing using an On-Demand panel which included 35 predisposition cancer genes associated with inherited cancer susceptibility. The percentage of germline pathogenic variant carriers was higher in the triple negative cohort. ATM, PALB2, BRIP1 and TP53 were the most non-BRCA mutated genes. Moreover, triple negative breast cancer patients without family history related who were identified as carriers were diagnosed at significantly earlier age. As conclusion, our study reinforces the usefulness of multigene panel testing in breast cancer cases but specifically in those with triple negative subtype regardless family history.
Subject(s)
Breast Neoplasms , Triple Negative Breast Neoplasms , Humans , Female , Triple Negative Breast Neoplasms/diagnosis , Triple Negative Breast Neoplasms/genetics , BRCA1 Protein/genetics , Breast Neoplasms/diagnosis , Breast Neoplasms/genetics , Breast Neoplasms/pathology , BRCA2 Protein/genetics , Early Detection of Cancer , Genetic Predisposition to Disease , Germ-Line Mutation , Genetic TestingABSTRACT
La biología molecular del cáncer ha permitido identificarnuevas dianas para atacar las células tumorales.Recientemente se ha propuesto la vía de señalizaciónde la insulina y el factor de crecimiento similar a la insulinacomo una de estas dianas. En esta revisión sedescribe su función biológica, los datos de laboratorioy estudios poblacionales que alertan de su papel enel cáncer y se describen los elementos claves de estavía de señalización: los ligandos (insulina, IGF1, IGF2),sus receptores y la cascada de señales intracelular quedesencadena su activación. Así mismo se revisan lasdistintas estrategias que se están investigando parabloquearla, algunas de las cuales ya se encuentran enestudios avanzados fase III. Los datos preliminares indicanque los fármacos diseñados para bloquear esta víapueden ser una nueva arma terapéutica para los pacientesoncológicos en un futuro próximo(AU)
The molecular biology of cancer has made it possibleto identify new targets for attacking tumourouscells. One of these recently proposed targets is the insulinand insulin-like growth factor signaling pathway.This review describes its biological function, laboratorydata, population studies that warn of its role incancer, and the key elements of this signaling pathway:the ligands (insulin, IGF1, IGF2), its receptors and thecascade of intracellular signals that trigger its activation.Also reviewed are the different strategies underinvestigation for blocking it, some of which are alreadyin phase III advanced studies. The preliminary data indicatethat the medicines designed for blocking this pathwaymight be a new therapeutic weapon for oncologypatients in the near future(AU)
Subject(s)
Humans , Neoplastic Cells, Circulating , Receptor, IGF Type 2/therapeutic use , Receptor, IGF Type 1/therapeutic use , Neoplasms/drug therapy , Carrier Proteins/physiology , Ligands , Metformin/pharmacokineticsABSTRACT
The molecular biology of cancer has made it possible to identify new targets for attacking tumourous cells. One of these recently proposed targets is the insulin and insulin-like growth factor signaling pathway. This review describes its biological function, laboratory data, population studies that warn of its role in cancer, and the key elements of this signaling pathway: the ligands (insulin, IGF1, IGF2), its receptors and the cascade of intracellular signals that trigger its activation. Also reviewed are the different strategies under investigation for blocking it, some of which are already in phase III advanced studies. The preliminary data indicate that the medicines designed for blocking this pathway might be a new therapeutic weapon for oncology patients in the near future.
Subject(s)
Insulin/physiology , Neoplasms/drug therapy , Somatomedins/physiology , Humans , Insulin Antagonists/therapeutic use , Signal Transduction , Somatomedins/antagonists & inhibitorsSubject(s)
Anesthesia, Spinal/adverse effects , Meningitis, Bacterial/etiology , Adult , Female , HumansABSTRACT
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No disponible
Subject(s)
Adult , Male , Female , Child , Humans , Magnetic Resonance Imaging , Tomography, X-Ray Computed , Tomography, X-Ray Computed , Anesthesia, Spinal , Hydranencephaly , Meningitis, Bacterial , HydranencephalyABSTRACT
Folk medicines are gaining great importance as information sources on traditional medicinal plants. The aim of this paper is the study of a plant traditionally employed by the Puna inhabitants: Werneria poposa Phil. Morphology of its secretory tissue and other histological diagnostic features, as well as the chemical composition of its essential oil, is described. Puna inhabitants use W. poposa mainly as an infusion for mountain sickness ("soroche"), stomach and hepatic disorders and cold. It is also used externally as a hot bath or unguent for rheumatic pains or traumas. Secretory tissues are schizogenous ducts in leaves and stems. Thirty-one components were detected in the essential oil by means of GC/MS analysis. Oil was characterized by the presence of high content of ß-pinene (21.7%), a-pinene (5.5%), terpinen-4-ol (5.3%), a-terpinene (5.2%), ß-phellandrene + 1,8-cineole (4.8%), isopulegol (4.8%) and ß-citronellal (4.6%). At the present time, W. poposa is consumed as a medicinal plant, mainly in the northwest of Argentina, not being commercialized in the urban centers.
