Clinical correlation of extensive-stage small-cell lung cancer genomics.

BACKGROUND: Genomic studies in small-cell lung cancer (SCLC) lag far behind those carried out in nonsmall-cell lung cancer (NSCLC). To date, most SCLC studies have evaluated patients with surgically resectable disease. Here we sought to evaluate the genomic mutation spectrum of 'every-day' SCLC patient tumors with extensive stage disease (ES-SCLC) and to correlate mutations with the main clinical outcomes of response to chemotherapy, progression-free (PFS) and overall (OS) survival. PATIENTS AND METHODS: A total of 50 SCLC patient tumors were examined in this study; targeted exome sequencing was obtained on 42 patients and whole-exome sequencing on 8 patients. Mutated genes were correlated with clinical outcomes using Kaplan-Meier methods (PFS, OS) and logistic regression (chemo-response). RB1 protein expression was detected by either western blotting of cultured cell lysates or immunohistochemistry of tumor specimens. RESULTS: In all, 39 patients had ES-SCLC; 15 patients had either primary refractory/resistant disease and 21 patients had sensitive disease. The two most frequently mutated genes were TP53 (86%) and RB1 (58%); other frequently mutated genes (>10% patients) were involved in epigenetic regulation as well as the mTOR pathway. We identified a number of low-frequency, targetable mutations, including RICTOR, FGFR1, KIT, PTCH1 and RET. Using multivariate analysis, RB1 was the only significant factor (P = 0.038) in predicting response to first-line chemotherapy, with an odds ratio of 5.58 comparing mutant RB1 with wild-type. Patients with mutant RB1 had both better OS (11.7 versus 9.1 months P = 0.04) and PFS (11.2 versus 8.6 months, P = 0.06) compared with patients with wild-type RB1. Interestingly, ∼25% of SCLC cell lines and tumor specimens expressed RB1 protein, possibly representing the subgroup with wild-type RB1. CONCLUSIONS: We found that SCLC tumors harboring no mutation in RB1 had a poor response to chemotherapy.

Subthreshold micropulse yellow laser (577 nm) in chronic central serous chorioretinopathy: safety profile and treatment outcome.

PURPOSE: To assess the safety and efficacy of a single session of subthreshold micropulse (SM) yellow laser (577 nm) in the treatment of chronic central serous chorioretinopathy (CSCR). METHODS: This was a retrospective analysis of 15 eyes of 13 patients with CSCR of >3 months duration who had been treated with SM yellow laser (577 nm). All patients had been treated using multiple spots of laser with a duty cycle of 10% over areas of focal and diffuse leak, as seen on fundus fluorescein angiography (FFA) and indocyanine green angiography (ICGA). Reduction in subretinal fluid height on spectral domain optical coherence tomography (SD-OCT) was used to measure the response to treatment. RESULTS: The mean follow-up was at 8 weeks (4-19 weeks). All eyes responded to treatment. The mean subretinal fluid height pre and post treatment was 232 and 49 µm, respectively, showing a 79% average reduction (P<0.001) in fluid height. There was no evidence of retinal pigment epithelium or retinal damage on SD-OCT, FFA, or fundus autofluorescence. Median visual improvement was one line on Snellen's visual acuity chart (P=0.015). Microperimetry was performed in eight eyes of which six eyes (75%) showed an improvement in the threshold values post treatment. CONCLUSION: SM yellow laser is an effective treatment option for chronic CSCR.

Variations in the cone packing density with eccentricity in emmetropes.

AIM: To describe the parafoveal cone arrangement in emmetropic subjects and its variations with eccentricity, meridians and change in axial length in Indian eyes. METHODS: We imaged 25 subjects using compact adaptive optics (AO) retinal camera prototype, the rtx1. Imaging was done at 1, 2, and 3° eccentricity from the fovea in four meridians: nasal, temporal, superior, and inferior. RESULTS: A statistically significant drop in the cone packing density was observed from 2 to 3° (2° eccentricity=25 350/mm(2) (5300/mm(2), 8400-34 800/mm(2)) 3° eccentricity=20 750/mm(2) (6000 mm(2), 9000-33 670/mm(2))) P<0.05. The spacing correspondingly increased with increase in distance from the fovea (2° eccentricity=6.9 µm (0.70 µm, 5.95-11.6 µm)) and 3°eccentricity=7.80 µm (1.00 µm, 6.5-13.5 µm) P<0.05. As the axial length increases, the cone density significantly decreases. Interocular variations were noted. CONCLUSION: With the advent of AO, visualization at the cellular level is now possible. Understanding the photoreceptor mosaic in the parafoveal space in terms of its density, spacing, and arrangement is crucial so as to detect early pathology and intervene appropriately. Newer therapeutic modalitites that are targeted at the cellular level like yellow micropulse laser, stem cells, gene therapy and so on may be better monitored in terms of safety and efficacy.

2,4,6-triamino-1,3,5-trinitrobenzene (TATB) and TATB-based formulations--a review.

This paper reviews the research and development work on 2,4,6-triamino-1,3,5-trinitrobenzene (TATB), and TATB-based formulations of other explosives. Syntheses including the production of nano-sized particles, analytical methods, thermophysical properties, performance, formulations, toxicity and safety of TATB are reviewed in this work.

Eight years of lung transplantation: experience of the National Research Institute of Tuberculosis and Lung Diseases.

BACKGROUND: Lung transplantation has evolved from an experimental procedure to a viable therapeutic option in many countries. In Iran, the first single-lung transplantation was performed in the year 2000, more than 3 decades after the first successful procedure in the world, and the first double-lung transplantation was performed in the year 2006. OBJECTIVE: To describe our 8-year experience in lung transplantation. PATIENTS AND METHODS: During 8 years, we performed 24 lung transplantation procedures. Underlying lung diseases were pulmonary fibrosis in 16 patients (66.6%); chronic obstructive pulmonary disease in 2 (8.3%); bronchiectasis in 5, including 2 patients with cystic fibrosis (20.8%), and alveolar microlithiasis in 1 (4.16%). Data for all patients were collected and analyzed. Procedures were carried out using standardized methods. The induction suppression regimen consisted of cyclosporine and methylprednisolone. Maintenance immunosuppression drugs were cyclosporine and mycophenolate mofetil, and tapering dosage of prednisolone. Patients were followed up with physical examinations, 3 times a week, as well as and cycle ergometry 3 times a week and spirometry and laboratory tests once a week and chest radiography per needed for up to 3 months posttransplantation. RESULTS: The longest survival time was 7.2 years, in a 60-year-old patient with idiopathic pulmonary fibrosis. Fourteen patients died, 8 as a result of hemodynamic instability and/or hemorrhage, 1 as a result of bone and fat emboli, 3 after cessation of drug and 2 of them after infection. CONCLUSION: Although lung transplantation is a complex procedure it can be performed in developing countries such as Iran.

Dispersion of chitosan on perlite for enhancement of copper(II) adsorption capacity.

Chitosan coated perlite beads were prepared by drop-wise addition of slurry, made of chitosan dissolved in oxalic acid and perlite, to an alkaline bath (0.7 M NaOH). The beads that contained 32% chitosan enhanced the accessibility of OH and amine groups present in chitosan for adsorption of copper ions. The experiments using Cu(II) ions were carried out in the concentration range of 50-4100 mg/L (0.78-64.1 mmol/L). Adsorption capacity for Cu(II) was pH dependent and a maximum uptake of 104 mg/g of beads (325 mg/g of chitosan) was obtained at pH 4.5 when its equilibrium concentration in the solution was 812.5 mg/L at 298 K. The XPS and TEM data suggested that copper was mainly adsorbed as Cu(II) and was attached to amine groups. The adsorption data could be fitted to one-site Langmuir adsorption model. Anions in the solution had minimal effect on Cu(II) adsorption by chitosan coated perlite beads. EDTA was used effectively for the regeneration of the bed. The diffusion coefficient of Cu(II) onto chitosan coated beads was calculated from the breakthrough curve and was found to be 2.02 x 10(-8) cm(2)/s.

Immunoprophylactic evaluation of a 37-kDa Brugia malayi recombinant antigen in lymphatic filariasis.

The Brugia malayi filarial antigens recognised preferentially by sera from an endemic normal population are considered to be potential vaccine candidates. By immunoscreening the cDNA library of the infective L3 stage of B. malayi with pooled endemic normal sera, a cDNA clone Bm-SL3 was identified. Analysis of sera from different patient groups with the rBm-SL3 protein showed it to be highly reactive with endemic normal sera compared to its reactivity with microfilaraemic and non-endemic normal sera. The immunoprotective efficacy of the rBm-SL3 antigen against B. malayi filarial infection was evaluated in susceptible host jirds (gerbils) (Meriones unguiculatus). Jirds immunised with the rBm-SL3 antigen showed 68% cytotoxicity against microfilariae and 67-69% cytotoxicity against infective larvae in in-vitro antibody-dependent cellular cytotoxicity assays and in-situ micropore chamber methods. Analysis of IgG subclasses against Bm-SL3 revealed a significant increase in IgG1 and IgG2 antibodies in endemic normal sera compared with other groups. Lymphocyte proliferation to Bm-SL3 was significantly higher in the endemic normal group compared with that in clinical and microfilarial carriers (p < 0.001). Significantly enhanced levels of IFN-gamma in the culture supernatant of peripheral blood mononuclear cells of endemic normal sera after stimulation with Bm-SL3 suggest that the cellular response in this group may have a Th1 bias.