EGFR Thr790Leu as a Potential Resistance Mechanism to First-Generation EGFR Tyrosine Kinase Inhibitor May Respond to Osimertinib in Patients With Lung Adenocarcinoma.

INTRODUCTION: It has been well established that EGFR Thr790Met is one of the major resistance mechanisms to first- and second-generation EGFR tyrosine kinase inhibitors (TKIs). Nevertheless, whether EGFR Thr790Leu (T790L), which shares the mutation site of Thr790 with EGFR Thr790Met, mediates resistance to EGFR TKIs remains elusive. The treatment options for patients harboring this rare mutation have not been reported. METHODS: Capture-based targeted ultradeep sequencing was performed on tumor and plasma samples collected at various treatment milestones from three patients with advanced lung adenocarcinoma undergoing targeted therapy. RESULTS: Needle biopsy of lymph node metastasis from patient 1 revealed EGFR T790L at disease progression on first-line treatment of gefitinib. Patient 2 had EGFR T790L identified from needle biopsy of lung tissue at disease progression on icotinib treatment. This patient was subsequently treated with osimertinib and achieved stable disease with a progression-free survival of 9 months. For patient 3, at disease recurrence after surgery, resected lung tumor tissue was retrieved for molecular profiling and revealed EGFR exon 19 deletion and EGFR T790L. The patient subsequently received osimertinib treatment and continued to benefit for 16 months and counting. She has maintained stable disease at the time of submission of this manuscript. CONCLUSIONS: We revealed for the first time that EGFR T790L may serve as a potential resistance mechanism to first-generation EGFR TKIs. We also report the first clinical evidence of efficacy generated by osimertinib in patients with lung adenocarcinoma harboring primary or acquired EGFR T790L, shedding light on treatment options for this subset of patients.

HRCT features distinguishing pre-invasive from invasive pulmonary adenocarcinomas appearing as ground-glass nodules.

OBJECTIVE: To investigate the high-resolution computed tomography (HRCT) features that distinguish lung adenocarcinomas in situ (AISs) and minimally invasive adenocarcinomas (MIAs) from invasive adenocarcinomas (IACs) appearing as ground-glass nodules (GGNs), and to select candidates for sublobar resection. METHODS: Two hundred and twenty-nine patients with 237 GGNs of less than 2 cm (139 AIS-MIA nodules and 98 IAC nodules) confirmed by surgery and pathology were retrospectively reviewed. The HRCT features of the AIS-MIAs and IACs were analysed and compared. Receiver operating characteristic (ROC) analyses were conducted to determine the cutoff values for the qualitative variables and their diagnostic performances. RESULTS: Significant differences were found in the density, nodule and solid component diameters, CT values of the ground-glass and solid components, lobulated shape, spiculated margin, abnormal pulmonary vein and artery, air bronchogram, and pleural indentation of the GGNs between the two groups. Multivariate and ROC analyses revealed that larger diameter of nodules (≥12.2 mm) and solid components (≥6.7 mm), and higher CT values of the solid components (≥ -192 HU) in the GGNs with air bronchogram were significantly associated with IACs. CONCLUSIONS: HRCT can identify distinguishing morphological features between AIS-MIAs and IACs, and is helpful for selecting candidates for sublobar resection. KEY POINTS: • IACs appearing as GGNs were often ≥ 12.2 mm in diameter. • IACs were often ≥ 6.7 mm in solid component diameter. • The solid components of the IACs often exhibited ≥ -192 HU. • IACs exhibited air bronchogram more frequently than AIS-MIAs.

A complex of poly(4-vinylpyridine) and tolane based hemi-phasmid benzoic acid: towards luminescent supramolecular side-chain liquid crystalline polymers.

A supramolecular side-chain liquid crystalline (LC) polymer P4VP(1)x was prepared using poly(4-vinylpyridine) and a tolane based hemi-phasmid benzoic acid. P4VP(1)x exhibits good processability, forming smectic and hexagonal columnar LC phases at different compositions. Its photoluminescence properties depend on the LC structures.

[Study on sexual behavior and HIV/STIs among miners in Yunnan province].

OBJECTIVE: This paper aims to describe human immunodeficiency virus/sexual transmitted infections (HIV/STIs) related knowledge, attitudes, practice and the prevalence of HIV/STIs amongst miners. METHODS: Two focus-group related discussions with a total number of 13 members including Community Advisory Boards (CAB) and 12 miners were conducted in a mining township in Yunnan province. Questionnaire surveys and HIV/STIs tests were conducted among 233 miners recruited by cluster sampling in two towns where the mines were located. RESULTS: The average age of respondents was 28 year old with 82.8% of them younger than 35 year old. 95.3% of the respondents attended the education level of junior middle school. AIDS related knowledge among miners was low. The percentage of right answers to the routes of transmission was only 54.4%. The ratio of self-reported prostitutes visits was 9.0%. The prevalence rates of Neisseria gonrrhoeae, HIV and Chlamydia trachomatis were 0.4%, 0.4%and 8.2% respectively. The correlation between Chlamydia trachomatis infection and education (P = 0.0347) was significant, and so was that between Chlamydia trachomatis infection and marriage status (P = 0.032). CONCLUSION: This study showed that the awareness of HIV/STIs prevention was limited and the rate of condom use was low, suggesting that miners needed to be viewed as a key population in HIV/STIs prevention and control.