Novel prognostic markers are warranted for gastrointestinal stromal tumours. Caveolin-1 is a multifunctional protein that proved to be associated with outcome in multiple tumour types. Aim of this study was to investigate Caveolin-1 expression and prognostic efficacy in a series of gastrointestinal stromal tumours.
Caveolin-1 expression was assessed by immunohistochemistry in a retrospective series of 66 gastrointestinal stromal tumours representative of the different molecular subtypes. Correlations with clinical, histopathological and molecular features were investigated. Statistical analyses were performed as appropriate.
Thirty-five cases out of 66 (53.0%) expressed Caveolin-1. Presence of Caveolin-1 expression correlated with favourable histopathologic and clinical traits, including a lower mitotic count (p=0.003) and lower relapse rate (p=0.005). Caveolin-1 expression also resulted associated with the presence of
mutations (p=0.010). Outcome analyses showed a favourable prognostic significance of Caveolin-1 expression in terms of relapse-free survival (HR=0.14; 95% CI=0.03 to 0.63) and overall survival (HR=0.29; 95% CI=0.11 to 0.74), even after adjusting for the mutational subgroup (relapse-free survival HR=0.14, 95% CI=0.04 to 0.44; overall survival HR=0.29, 95% CI=0.11 to 0.51) and imatinib treatment (relapse-free survival HR=0.14, 95% CI=0.02 to 0.81; overall survival HR=0.29, 95% CI=0.17 to 0.48).
Caveolin-1 represents a novel prognostic marker in gastrointestinal stromal tumours. Further studies are warranted to validate these results and to explore the mechanisms linking Caveolin-1 expression with the
oncogenic pathway.
Caveolin-1 represents a novel prognostic marker in gastrointestinal stromal tumours. Further studies are warranted to validate these results and to explore the mechanisms linking Caveolin-1 expression with the PDGFRA oncogenic pathway.
Injection pressure monitoring using in-line devices is affordable and easy to implement into a regional anesthesia practice. However, solid evidence regarding their performance is lacking. We aimed to evaluate if opening injection pressure (OIP), measured with a disposable in-line pressure monitor, can prevent intraneural (subepineural) injection using 15 pound per square inch (PSI) as the reference safety threshold.
An isolated nerve model with six tibial and six common peroneal nerves from three unembalmed fresh cadavers was used for this observational study. A mixture of 0.5% ropivacaine with methylene blue was injected intraneurally at a rate of 10 mL/min, to a maximum of 3 mL. OIP was recorded for each injection as well as evidence of intraneural contrast. Injected volume at 15 and 20 PSI was recorded, and when it leaked out the epineurium, if it occurred.
In all cases, OIP was<15 PSI and intraneural contrast was evident before the safety threshold. The 15-20 PSI mark was attained in 5 of 12 injections (41%), with a median injected volume of 0.9 mL (range 0.4-2.3 mL). Peak pressure of >20 PSI was reached in two injections (at 0.6 mL and 2.7 mL). Contrast leaked out the epineurium in 11 of 12 injections (91%) with a median injected volume of 0.6 mL (range 0.1-1.3 mL).
Our results suggest that in-line pressure monitoring may not prevent intraneural injection using an injection pressure of 15 PSI as reference threshold. Due to the preliminary nature of our study, further evidence is needed to demonstrate clinical relevance.
Our results suggest that in-line pressure monitoring may not prevent intraneural injection using an injection pressure of 15 PSI as reference threshold. Due to the preliminary nature of our study, further evidence is needed to demonstrate clinical relevance.The family of AGC kinases not only regulate cellular biology by phosphorylating substrates, but are themselves controlled by phosphorylation. Phosphorylation generally occurs at two conserved regions in these kinases a loop near the entrance to the active site, termed the activation loop, that correctly aligns residues for catalysis, and a C-terminal tail whose phosphorylation at a site termed the hydrophobic motif stabilizes the active conformation. Whereas phosphorylation of the activation loop is well established to be catalyzed by the phosphoinositide-dependent kinase 1 (PDK1), the mechanism of phosphorylation of the C-tail hydrophobic motif has been controversial. For a subset of AGC kinases, which includes most protein kinase C (PKC) isozymes and Akt, phosphorylation of the hydrophobic motif in cells was shown to depend on mTORC2 over 15 years ago, yet whether by direct phosphorylation or by another mechanism has remained elusive. The recent identification of a novel and evolutionarily conserved phosphorylation site on the C-tail termed the TOR-Interaction Motif (TIM) has finally unraveled the mystery of how mTORC2 regulates its client kinases. mTORC2 does not directly phosphorylate the hydrophobic motif, rather it converts kinases such as PKC and Akt into a conformation that can ultimately autophosphorylate at the hydrophobic motif. Identification of the direct mTOR phosphorylation that facilitates auto-regulation of the C-tail hydrophobic motif revises the activation mechanisms of mTOR-regulated AGC kinases. This new twist to an old tail opens avenues for therapeutic intervention. Significance Statement The enzyme mTORC2 has been an enigmatic regulator of AGC kinases such as protein kinase C (PKC) and Akt. The recent discovery of a motif named the TOR Interaction Motif in the C-tail of these kinases solves the mystery mTORC2 marks these kinases for maturity by, ultimately, facilitating autophosphorylation another C-tail site, the hydrophobic motif.While the COVID-19 pandemic progresses, politicians and media outlets in the USA have compared the pandemic with World War II (WWII). Though women's reproductive health has been affected by both COVID-19 and WWII, these specific health needs are not included in either event's mainstream narrative. ODQ This article explores the pandemic's war metaphor through the lens of women's reproductive health, arguing for a reframing of the metaphor. Narrative-building determines how health needs are perceived and addressed. A modification of the WWII metaphor can ensure that the narrative formulating around COVID-19 is inclusive of the women's reproductive health needs that are eminently present.ODQ
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