No abstract

Lessons Learned. Weekly nanoparticle albumin‐bound‐paclitaxel (75 mg/m2) in combination with carboplatin (area under the curve 6 mg/mL/min) in elderly patients with previously untreated, advanced non‐small cell lung cancer showed favorable efficacy, was well tolerated, and showed less neuropathic toxicity.This modified regimen offers potential for the treatment of elderly patients.Background.The CA031 trial suggested weekly nanoparticle albumin‐bound‐paclitaxel (nab‐PTX) was superior in efficacy to paclitaxel (PTX) once every 3 weeks when combined with carboplatin (CBDCA) for advanced non‐small cell lung cancer (NSCLC) patients; a subgroup analysis of elderly patients looked promising. In a multicenter phase II trial, we prospectively evaluated the efficacy and tolerability of modified CBDCA plus weekly nab‐PTX for elderly patients with untreated advanced NSCLC.Methods.Eligible patients received CBDCA (area under the curve [AUC] 6 mg/mL/min) on day 1 and nab‐PTX (75 mg/m2) on days 1, 8, and 15 every 4 weeks. The primary endpoint was an overall response rate (ORR), and secondary endpoints were progression‐free survival (PFS), overall survival (OS), and toxicity.Results.Of 32 patients (median age of 78 years), 84% were male, 56% had stage IV NSCLC, and 56% had squamous cell carcinoma. ORR and disease control rates were 50% (95% confidence interval (CI): 33–67) and 94% (95% CI: 85–100), respectively. Median PFS and OS were 6.4 months (95% CI: 4.8–8.0) and 17.5 months (95% CI: 11.9–23.1), respectively. Grade ≥3 toxicities were neutropenia (47%), leukopenia (38%), anemia (34%), thrombocytopenia (25%), and anorexia (9%). Febrile neutropenia and treatment‐related deaths were not observed.Conclusion.Modified CBDCA plus weekly nab‐PTX demonstrated significant efficacy and acceptable toxicities in elderly patients with advanced NSCLC.

No abstract

Our study revealed biological, structural, and probably clinical features of the delE746 form of EGFR.

Pial arteriovenous fistulas (AVFs) are known as rare cerebrovascular lesions. They are composed of >/= 1 arterial feeding vessels and a single draining vein that usually has high perfusion pressure and generally occur in infants. Cases involving adults are very rare and the developmental mechanisms and natural history of these lesions remain unknown. The authors present a case of multiple pial AVFs in an adult in whom the lesions developed after radiosurgical treatment of dural AVFs. Direct disconnection of pial arterial supplies was performed, and the abnormal shunts were successfully eliminated. The authors report the clinical course of this case and discuss the characteristics of and treatment strategy for multiple pial AVFs, reviewing the published literature.

Spontaneous simultaneous multivessel coronary artery spasm in patients with acute myocardial infarction (AMI) is uncommon. A 79-year-old Japanese man was transferred to this hospital because of severe prolonged chest pain and faintness. Left coronary angiography revealed total occlusion of the left anterior descending and the left circumflex coronary arteries. Moreover, right coronary angiography revealed 99% stenosis of the right coronary artery. After intracoronary administration of nicorandil, left coronary artery and right coronary artery angiography revealed no organic stenosis or thrombus. This is the first report in which simultaneous 3-vessel spasm was documented by emergency angiography in AMI.

A prognostic association between the novel chaperone protein-L-isoaspartate (D-aspartate) O-methyltransferase (PIMT) and lung adenocarcinoma has recently been reported. Here, we evaluated the functional roles of PIMT in the progression of lung adenocarcinoma. PIMT expression was detectable in 6 lung adenocarcinoma cell lines: A549, H441, H460, H1650, Calu 1, and Calu 6 cell lines. In A549 and H441 cells, knockdown by PIMT using silencing RNA of PIMT (si-PIMT) and/or small hairpin-RNA (sh-PIMT) induced a decrease in the expression of E-cadherin with an increase in vimentin expression, indicating that the epithelial to mesenchymal transition (EMT) was induced. Cell mobility, including migration and invasion capability, was increased in sh-PIMT A549 stable and si-PIMT H441 cells compared to in control cells. Endoplasmic reticulum (ER) stress, such as Thapsigargin (Tg) stress and hypoxia, induced EMT in A549 cells but not in other cell types, with an increase in GRP78 expression, whereas overexpression of PIMT reduced the EMT and cell invasion under stress conditions. The expression of hypoxia inducible factor-1 alpha (HIF1α) and Twist increased in sh-PIMT A549 and si-PIMT H441 cells, and Tg stress increased HIF1α expression levels in A549 cells in a dose-dependent manner. Moreover, LW6, an HIF1α inhibitor, reduced EMT, cancer invasion, and the levels of Twist in sh-PIMT A549 cells. Our results indicate that deficiency of supplemental PIMT expression under ER stress facilitates EMT and cell invasion in some cell types of lung adenocarcinoma.

Objective-To investigate the value of a giant negative T wave ( > 1.0 mV) in precordial leads of 12-lead electrocardiograms in the acute phase of Q wave myocardial infarction as a predictor of myocardial salvage. Methods-Coronary angiographic and electrocardiographic findings, left ventricular ejection fraction in the chronic stage, and levels of cardiac enzymes were compared in patients with myocardial infarction with (group GNT, n = 31) and without (group N, n = 20) a giant negative T wave. GNT patients were divided into two subgroups according to the presence (GNT:R[+], n = 10) or absence (GNT: R[ -J, n = 21) of R wave recovery with an amplitude > 01 mV in at least one lead that had shown Q waves. Results-The maximum level of creatine kinase and the total creatine kinase were lower in group GNT compared with group N (P < 0.05). The left ventricular ejection fraction was higher in group GNT than in group N (P < 0.05). The maximum creatine kinase and total creatine kinase were lower in GNT:R(+) than in GNT:R(-) (P < 0.01). The left ventricular ejection fraction was higher in GNT:R(+) than in GNT:R(-) (P < 0.01). The frequency of R wave recovery was significantly higher when giant negative T waves appeared within 100 h of myocardial infarction or when the maximum potential was i 1-4 mV. The appearance of a giant negative T wave > 1'4 mV had a sensitivity of 90%, a specificity of 71-4%, a diagnostic accuracy of 77-4%, a positive predictive value of 60%, and a negative predictive value of 93-8% for prediction of R wave recovery. Conclusions-The appearance of a giant negative T wave, especially within 100 h of the onset of myocardial infarction, with a maximum potential of i 1'4 mV, may predict a reappearance of the R wave and a better left ventricular function in patients in the chronic stage of anterior myocardial infarction. (Heart 1996;75:229-234)