19 research outputs found
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Gene expression of the IGF pathway family distinguishes subsets of gastrointestinal stromal tumors wild type for KIT and PDGFRA
Gastrointestinal stromal tumors (GISTs) arise from the interstitial cells of Cajal (ICCs) and are the most common mesenchymal neoplasm of the gastrointestinal tract. While the majority of GISTs harbor activating mutations in either the v-kit Hardy-Zuckerman feline sarcoma viral oncogene homolog (KIT) or platelet-derived growth factor receptor alpha (PDGFRA) tyrosine kinases, approximately 10–15% of adult GISTs and 85% of pediatric GISTs lack such mutations. These “wild-type” GISTs have been reported to express high levels of the insulin-like growth factor 1 receptor (IGF1R), and IGF1R-targeted therapy of wild-type GISTs is being evaluated in clinical trials. However, it is not clear that all wild-type GISTs express IGF1R, because studies to date have predominantly focused on a particular subtype of gastric wild-type GIST that is deficient in the mitochondrial succinate dehydrogenase (SDH) complex. This study of a series of 136 GISTs, including 72 wild-type specimens, was therefore undertaken to further characterize wild-type GIST subtypes based on the relative expression of transcripts encoding IGF1R. Additional transcripts relevant to GIST biology were also evaluated, including members of the IGF-signaling pathway (IGF1, IGF2, and insulin receptor [INSR]), neural markers (CDH2[CDH: Cadherin], neurofilament, light polypeptide, LHX2 [LHX: LIM homeobox], and KIRREL3 [KIRREL: kin of IRRE like]), KIT, PDGFRA, CD34, and HIF1A. Succinate dehydrogenase complex, subunit B protein expression was also assessed as a measure of SDH complex integrity. In addition to the previously described SDH-deficient, IGF1Rhigh wild-type GISTs, other SDH-intact wild-type subpopulations were defined by high relative expression of IGF1R, neural markers, IGF1 and INSR, or low IGF1R coupled with high IGF2. These results underscore the complexity and heterogeneity of wild-type GISTs that will need to be factored into molecularly-targeted therapeutic strategies
Acute kidney failure secondary to very severe hypercalcaemia from primary hyperparathyroidism
La crisis hipercalcémica es una forma de presentación poco frecuente del hiperparatiroidismo primario. Solo existen pequeñas series de casos reportadas en la literatura1 and 2. Se caracteriza por hipercalcemia severa, insuficiencia renal y alteración del estado de conciencia. Presentamos el caso de un paciente de 70 años, que ingresa por fracaso renal agudo desencadenado por una crisis de hipercalcemia en el contexto de un hiperparatiroidismo primario no conocido previamente. Se discute la conducta terapéutica y la evolución del paciente
SELNET clinical practice guidelines for bone sarcoma
Bone sarcoma are infrequent diseases, representing < 0.2% of all adult neoplasms. A multidisciplinary management within reference centers for sarcoma, with discussion of the diagnostic and therapeutic strategies within an expert multidisciplinary tumour board, is essential for these patients, given its heterogeneity and low frequency. This approach leads to an improvement in patient's outcome, as demonstrated in several studies. The Sarcoma European Latin-American Network (SELNET), aims to improve clinical outcome in sarcoma care, with a special focus in Latin-American countries. These Clinical Practice Guidelines (CPG) have been developed and agreed by a multidisciplinary expert group (including medical and radiation oncologist, surgical oncologist, orthopaedic surgeons, radiologist, pathologist, molecular biologist and representatives of patients advocacy groups) of the SELNET consortium, and are conceived to provide the standard approach to diagnosis, treatment and follow-up of bone sarcoma patients in the Latin-American context
Acute kidney failure secondary to very severe hypercalcaemia from primary hyperparathyroidism
IGF-I, leptina, insulina e proteínas associadas à qualidade do plasma seminal: ação local
É possível que a expressividade de alguns elementos do plasma seminal dos bovinos, como proteínas e hormônios, possa servir como marcadores para sêmende alta ou baixa fertilidade. Vários estudos têm demonstrado a associação de proteínas do plasma seminalcom a fertilidade de touros. Dentre as mais estudadas, destacam-se aquelas com afinidade à heparina, que exercem importantes papéis na capacitaçãoespermática e na reação acrossômica. Alguns fatoresendócrinos e/ou locais, podem estar associados à expressividadee/ou função destas proteínas, auxiliandonas condições espermáticas favoráveis à fecundação. Dentre estes, destacam-se a insulina, a leptina e o fatorde crescimento semelhante à insulina do tipo I. Assim sendo, evidenciam diferenças entre animais,estando associados à estrutura e as condições metabólicasda célula espermática, auxiliando na determinação da qualidade do plasma seminal. Desta maneira,o estudo das proteínas do plasma seminal associadoà condição metabólica destes hormônios, presentesneste meio, pode servir como importante parâmetrode avaliação da condição reprodutiva do macho
IGF-I, leptina, insulina e proteínas associadas à qualidade do plasma seminal: ação local
It is possible that the expression of some elements in seminal plasma, such as proteins and hormones,may act as markers of quality. Several studies havedemonstrated an association of seminal plasma proteins with fertility. Among the most studied, there are the proteins with affinity to heparin, which play an important role in sperm capacitation and acrosome reaction. Some endocrine factors and/or locals maybe associated with the expression and function ofthese proteins, aiding in sperm condition conduciveto fertilization. Among them stand out as insulin,leptin and growth factor insulin-like type I. Thesefactors may highlight the differences between these animals because they are associated with the metabolic condition and structure of sperm cells, aidingin determining the quality of seminal plasma. Thus,the study of seminal plasma proteins associated with the metabolic condition of these hormones are presentin this medium can serve as a new parameter for assessment of male reproductive condition.É possível que a expressividade de alguns elementos do plasma seminal dos bovinos, como proteínas e hormônios, possa servir como marcadores para sêmende alta ou baixa fertilidade. Vários estudos têm demonstrado a associação de proteínas do plasma seminalcom a fertilidade de touros. Dentre as mais estudadas, destacam-se aquelas com afinidade à heparina, que exercem importantes papéis na capacitaçãoespermática e na reação acrossômica. Alguns fatoresendócrinos e/ou locais, podem estar associados à expressividadee/ou função destas proteínas, auxiliandonas condições espermáticas favoráveis à fecundação. Dentre estes, destacam-se a insulina, a leptina e o fatorde crescimento semelhante à insulina do tipo I. Assim sendo, evidenciam diferenças entre animais,estando associados à estrutura e as condições metabólicasda célula espermática, auxiliando na determinação da qualidade do plasma seminal. Desta maneira,o estudo das proteínas do plasma seminal associadoà condição metabólica destes hormônios, presentesneste meio, pode servir como importante parâmetrode avaliação da condição reprodutiva do macho