20 research outputs found
Membrane-anchored growth factor, HB-EGF, on the cell surface targeted to the inner nuclear membrane
Heparin-binding EGF-like growth factor (HB-EGF) is synthesized as a type I transmembrane protein (proHB-EGF) and expressed on the cell surface. The ectodomain shedding of proHB-EGF at the extracellular region on the plasma membrane yields a soluble EGF receptor ligand and a transmembrane-cytoplasmic fragment (HB-EGF-CTF). The cytoplasmic domain of proHB-EGF (HB-EGF-cyto) interacts with transcriptional repressors to reverse their repressive activities. However, how HB-EGF-cyto accesses transcriptional repressors is yet unknown. The present study demonstrates that, after exposure to shedding stimuli, both HB-EGF-CTF and unshed proHB-EGF translocate to the nuclear envelope. Immunoelectron microscopy and digitonin-permeabilized cells showed that HB-EGF-cyto signals are at the inner nuclear membrane. A short sequence element within the HB-EGF-cyto allows a transmembrane protein to localize to the nuclear envelope. The dominant-active form of Rab5 and Rab11 suppressed nuclear envelope targeting. Collectively, these data demonstrate that membrane-anchored HB-EGF is targeted to the inner nuclear membrane via a retrograde membrane trafficking pathway
Pediatric symptomatic Rathke cleft cyst compared with cystic craniopharyngioma
Introduction: Symptomatic Rathke cleft cysts (RCCs) are rarely detected in neuroradiological screening and are less commonly found in children than in adults. However, when RCCs are observed in children, it is important to carefully distinguish a RCC from a cystic craniopharyngioma (CP) even if surgically treated or conservatively followed up. Methods: We conducted a retrospective review of clinical data from 11 patients with symptomatic RCCs whose ages were under 18 years and compared the data with data from 15 age- and sex-matched patients with cystic CP who were treated at our institute. Results: The mean age of the patients with RCCs was 12.2 years (range, 6–18). There were six males and five females. As initial symptoms, nine patients presented with headache, while two each had impaired visual function, diabetes insipidus, and activity loss. The 14 patients with CP suffered from impaired visual function. Magnetic resonance imaging (MRI) mainly showed hyperintensity on T1-weighted images (WIs) and hypointensity on T2-WI in patients with RCC. However, patients with CP had characteristic hyperintensity on T2-WI. The average maximum diameter of the RCCs was 19.0 mm on average (range, 8–33 mm). The RCCs were thus significantly smaller than CPs (34.9 mm; range, 21–54 mm). The RCCs were usually oval or dumbbell-shaped and regular in appearance, while the larger CPs were lobular and irregular. A preoperative endocrinological evaluation revealed insufficiencies in four axes in five patients with RCC. Postoperative endocrinological status improved in three patients, remained unchanged in three, and worsened in one. The gonadotropin axis was damaged in a majority (nine) of the patients with CP preoperatively. Postoperative evaluation revealed deficits in five axes in 14 patients with CP, which is a significantly different trend than observed in patients with RCC. Eight patients underwent surgical procedures (transsphenoidal surgery (TSS) in four, craniotomy in four). Two of these patients experienced a recurrence of the cysts. One of these patients subsequently underwent two craniotomies followed by radiation and other underwent TSS. Among the three conservatively treated patients, two experienced a transient worsening of their symptoms along with cyst enlargement. However, none of the three conservatively treated patients required an operation. Conclusions: When RCCs become symptomatic in children, the most common symptom they lead to is headache. The cysts are commonly small, regular, and oval in shape. Hypointensity of cyst contents on MRI is a characteristic of RCCs, which distinguishes them from CPs. Surgical intervention can be effective and lead to the relief of symptoms without a high rate of complications. However, there seems to be a relatively high recurrence rate following surgery. Thus, if the patient’s symptoms remain minor, the surgical treatment option should be used only when prudent, as the patient’s symptoms may improve over time. © 2016 Springer-Verlag Berlin HeidelbergIn Press / Embargo Period 12 month
<Book Review> Heritage Language Education : A New Field Emerging", Donna M. Brinton, Olga Kagan, and Susan Bauckus (eds.), NY: Routeledge, 2008.
Dietary Effect of Yeast Extract of Glutathione on Lipid Metabolism and Immune Function of Sprague-Dawley Rats
Hypotension Associated with Prone Body Position: A Possible Overlooked Postural Hypotension
EFFICACY AND SIGNIFICANCE OF A CONSULTING CLINIC FOR RELATED FAMILY DONORS IN ALLOGENEIC HEMATOPOIETIC CELL TRANSPLANTATION AT THE DEPARTMENT OF TRANSFUSION MEDICINE AND CELL THERAPY
Exploratory analysis of immunochemotherapy compared to chemotherapy after EGFR‐TKI in non–small cell lung cancer patients with EGFR mutation: A multicenter retrospective study
Abstract Background Patients with epidermal growth factor receptor (EGFR)‐mutated, advanced non–small cell lung cancer have received immunochemotherapy as one of the treatment options after tyrosine kinase inhibitor (TKI) failure. Methods We retrospectively examined EGFR‐mutant patients treated with atezolizumab‐bevacizumab‐carboplatin‐paclitaxel (ABCP) therapy or platinum‐based chemotherapy (Chemo) after EGFR‐TKI therapy at five institutions in Japan. Results A total of 57 patients with EGFR mutation were analyzed. The median progression‐free survival (PFS) and overall survival (OS) in the ABCP (n = 20) and Chemo (n = 37) were 5.6 and 20.9 months, 5.4 and 22.1 months, respectively (PFS, p = 0.39; OS, p = 0.61). In programmed death‐ligand 1 (PD‐L1)–positive patients, median PFS in the ABCP group was longer than in the Chemo group (6.9 vs. 4.7 months, p = 0.89). In PD‐L1–negative patients, median PFS in the ABCP group was significantly shorter than in the Chemo group (4.6 vs. 8.7 months, p = 0.04). There was no difference in median PFS between the ABCP and Chemo groups in the subgroups of brain metastases, EGFR mutation status, or chemotherapy regimens, respectively. Conclusion The effect of ABCP therapy and chemotherapy was comparable in EGFR‐mutant patients in a real‐world setting. The indication for immunochemotherapy should be carefully considered, especially in PD‐L1–negative patients