RESUMO
We evaluated 328 patients (34.8% African American [AA]; 65.2% White American [WA]) with hormone receptor-positive, HER2/neu-negative breast cancer. Mean age (60 years); mean tumor size (1.6 and 1.7 cm for AA and WA, respectively) were similar, and mean BMI was higher for AA (33 vs 29.8; P = 0.001). Recurrence score (RS) distribution was similar- 8.3% AA and 5.9% WA with high RS (≥31). No significant differences were observed in delivery of chemotherapy stratified by score. With median follow-up 27.2 months for AA and 33.4 months for WA, distant recurrence occurred in 1.0% and 1.6%, respectively (P = 1). Our results suggest comparable RS utility in AA and WA patients.
Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Transcriptoma , Adulto , Negro ou Afro-Americano/genética , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/terapia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Prognóstico , Receptor ErbB-2/metabolismo , População Branca/genéticaRESUMO
GLI transport to the primary cilium and nucleus is required for proper Hedgehog (HH) signaling; however, the mechanisms that mediate these trafficking events are poorly understood. Kinesin-2 motor proteins regulate ciliary transport of cargo, yet their role in GLI protein function remains unexplored. To examine a role for the heterotrimeric KIF3A-KIF3B-KAP3 kinesin-2 motor complex in regulating GLI activity, we performed a series of structure-function analyses using biochemical, cell signaling and in vivo approaches that define novel specific interactions between GLI proteins and two components of this complex, KAP3 and KIF3A. We find that all three mammalian GLI proteins interact with KAP3 and we map specific interaction sites in both proteins. Furthermore, we find that GLI proteins interact selectively with KIF3A, but not KIF3B, and that GLI interacts synergistically with KAP3 and KIF3A. Using a combination of cell signaling assays and chicken in ovo electroporation, we demonstrate that KAP3 interactions restrict GLI activator function but not GLI repressor function. These data suggest that GLI interactions with KIF3A-KIF3B-KAP3 complexes are essential for proper GLI transcriptional activity.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas do Citoesqueleto/metabolismo , Cinesinas/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Complexos Multiproteicos/metabolismo , Fatores de Transcrição/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Células COS , Galinhas , Chlorocebus aethiops , Proteínas do Citoesqueleto/genética , Humanos , Cinesinas/genética , Proteínas Associadas aos Microtúbulos/genética , Complexos Multiproteicos/genética , Fatores de Transcrição/genética , Transcrição Gênica/fisiologia , Proteína GLI1 em Dedos de ZincoRESUMO
Goals/Purpose: To evaluate the effects of preoperative oral diazepam on the postoperative course of patients undergoing primary augmentation mammoplasty in an outpatient surgical center. Methods/Technique: A retrospective review was conducted of 189 patients undergoing primary breast augmentation at an outpatient surgical center from 2012 to 2015. Patients receiving same-day premedication with oral diazepam were compared with a control group without premedication. Patients with combined surgical procedures were excluded with the exception of minor, superficial procedures. Patient demographics, perioperative medication use, operative details, and postoperative numeric pain scale (0-10) scores were collected. Results/Complications: Ninety-three patients (49%) were included in the premedication group and 96 (51%) in the control group. Difference in age, body mass index, implant size, and intraoperative opioid use were not statistically significantly different between the treatment and control groups (P > .05). No difference was noted in postoperative nausea, emesis, or antiemetic use between the 2 groups. The operative time was slightly longer in the control group (64.5 minutes vs 58.5 minutes, P = .006). Immediate postoperative pain (3.6 vs 4.4) and time to discharge (101 minutes vs 110 minutes) were slightly decreased in the premedication group; however, these values did not reach statistical significance. Intraoperative narcotic use was the same between groups, but postoperative narcotic pain medication use was higher in the premedication group (9.68 mg vs 8.26 mg, P = .036). Predischarge pain scores (2.87 vs 2.29, P = .006) were also noted to be slightly higher in the premedication group. Conclusions: Preoperative diazepam administration does not significantly decrease time to discharge in primary breast augmentation mammoplasty. Furthermore, its use may result in increased postoperative narcotic use and higher pain scores at the time of discharge.