Mutations within the tyrosine kinase domain of EGFR gene specifically occur in lung adenocarcinoma patients with a low exposure of tobacco smoking

Somatically acquired mutations in the epidermal growth factor receptor (EGFR) gene in lung cancer are associated with significant clinical responses to gefitinib, a tyrosine kinase inhibitor that targets EGFR. We screened the EGFR in 469 resected tumours of patients with lung cancer, which included 322 adenocarcinomas, 102 squamous cell carcinomas, 27 large cell carcinomas, 13 small cell carcinomas, and five other cell types. PCR with a specific condition was performed to identify any deletion in exon 19, while mutant-allele-specific amplification was performed to identify a mutation in codon 858 of exon 21. EGFR mutations were found in 136 cases (42.2%) with adenocarcinoma, in one case with large cell carcinoma, and in one case with pleomorphic carcinoma. An in-frame deletion in exon 19 was found in 62 cases while an L858R mutation was found in 77 cases. In the 322 cases with adenocarcinoma, these mutations were more frequently found in women than in men (P=0.0004), in well differentiated tumours than in poorly differentiated tumours (P=0.0014), and in patients who were never smokers than in patients who were current/former smokers (P<0.0001). The mutation was more frequently observed in patients who smoked ⩽20 pack-year, and in patients who quit at least 20 years before the date of diagnosis for lung cancer. The K-ras mutations were more frequently found in smokers than in never smokers, and in high-dose smokers than in low-dose smokers. In conclusion, the mutations within the tyrosine kinase domain of EGFR were found to specifically occur in lung adenocarcinoma patients with a low exposure of tobacco smoking

Gefitinib induction followed by chemoradiotherapy in EGFR-mutant, locally advanced non-small-cell lung cancer: LOGIK0902/OLCSG0905 phase II study

Background: The role of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) induction coupled with standard concurrent chemoradiotherapy (CRT) is unclear in unresectable, stage III, EGFR-mutant non-small-cell lung cancer (NSCLC). Therefore, a phase II trial was conducted to evaluate the efficacy and safety of gefitinib induction followed by CRT in this disease setting. Patients and methods: Patients with unresectable, EGFR-mutant, stage III NSCLC were administered gefitinib monotherapy (250 mg/day) for 8 weeks. Subsequently, patients without disease progression during induction therapy were administered cisplatin and docetaxel (40 mg/m(2) each) on days 1, 8, 29, and 36 with concurrent radiotherapy at a total dose of 60 Gy. The primary endpoint was the 2-year overall survival (OS) rate, which was hypothesized to reach 85%, with a threshold of the lower limit of 60%. Results: Twenty patients (median age: 66 years; male/female: 9/11; histology: 20 adenocarcinoma; stage IIIA/IIIB: 9/11; and exon 19/21: 10/10) were enrolled. The 2-year OS rate was 90% (90% confidence interval: 71.4% to 96.8%), indicating that this trial met the primary objective. The overall response rate and 1- and 2-year progression-free survival rates were 85.0%, 58.1%, and 36.9%, respectively. Grade >= 3 adverse events (>10%) included hepatic toxicity during the induction phase and neutropenia and febrile neutropenia in the CRT phase. Radiation pneumonitis grade >= 3 or treatment-related death did not occur. Conclusions: This is the first prospective study to demonstrate the favorable efficacy and safety of EGFR-TKI induction followed by standard CRT in EGFR-mutant, stage III NSCLC. Further confirmatory studies are needed

Calcified multilocular thymic cyst associated with thymoma: a case report

<p>Abstract</p> <p>Introduction</p> <p>There are few case reports of thymoma with a thymic cyst. Such an association renders it difficult for any pathologist to differentiate from other neoplasms, such as a cystic thymoma.</p> <p>Case presentation</p> <p>A 50-year-old Berber woman from Morocco was admitted with a chronic cough of more than 10 years duration. Her medical history and physical examination were normal. Anterior chest radiography demonstrated a calcified opacity in her right anterior mediastinum. A chest-computed tomogram revealed a round cystic tumor, with significant calcification in her right anterior mediastinum. A surgical exploration was performed. The tumor seemed to be a well-encapsulated and totally calcified lesion, arising from the right lobe of her thymus. It was removed by partial resection of her thymus. Through histology, the calcified tumor exhibited some areas of multilocular fibrous-wall cysts. These cysts were partially lined by small cuboidal cells with severe chronic inflammation and an AB thymoma that arose from the wall of the cyst.</p> <p>Conclusion</p> <p>Greater attention should be given to multilocular thymic cysts, to exclude the possibility of neoplasm, especially when the cyst wall is thickened.</p

Excited State Interactions in Flurbiprofen-Tryptophan dyads

This document is the Accepted Manuscript version of a Published Work that appeared in final form in The Journal of Physical Chemistry B, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://doi.org/10.1021/jp071301z[EN] Fluorescence and laser-flash photolysis measurements have been performed on two pairs of diastereomeric dyads that contain the nonsteroidal anti-inflammatory drug (S)- or (R)-flurbiprofen (FBP) and (S)-tryptophan (Trp), which is a relevant amino acid present in site I of human serum albumin. The fluorescence spectra were obtained when subjected to excitation at 266 nm, where similar to 60% of the light is absorbed by FBP and similar to 40% is absorbed by Trp; the most remarkable feature observed in all dyads was a dramatic fluorescence quenching, and the residual emission was assigned to the Trp chromophore. In addition, an exciplex emission was observed as a broad band between 380 and 500 nm, especially in the case of the (R,S) diastereomers. The fluorescence lifetimes (tau(F)) at lambda(em) = 340 nm were clearly shorter in the dyads than in Trp-derived model compounds; in contrast, the values of tau(F) at lambda(em) = 440 nm (exciplex) were much longer. On the other hand, the typical FBP triplet-triplet transient absorption spectrum was obtained when subjected to laser-flash photolysis, although the signals were less intense than when FBP was directly excited under the same conditions. The main photophysical events in FBP-Trp dyads can be summarized as follows: (1) most of the energy provided by the incident radiation at 266 nm reaches the excited singlet state of Trp ((1)Trp*), either via direct absorption by this chromophore or by singlet singlet energy transfer from excited FBP ((FBP)-F-1*); (2) a minor, yet stereoselective deactivation of (FBP)-F-1* leads to detectable exciplexes and/or radical ion pairs; (3) the main process observed is intramolecular (1)Trp* quenching; and (4) the first triplet excited-state of FBP can be populated by triplet-triplet energy transfer from excited Trp or by back-electron transfer within the charge-separated states.Financial support from the MCYT (CTQ2004-03811) and the Generalitat Valenciana (GV06/099) is gratefully acknowledged. Author I.V. thanks MEC for a fellowship.Vayá Pérez, I.; Jiménez Molero, MC.; Miranda Alonso, MÁ. (2007). Excited State Interactions in Flurbiprofen-Tryptophan dyads. The Journal of Physical Chemistry B. 111(31):9363-9371. https://doi.org/10.1021/jp071301zS936393711113