instruction:
In this task, you are given a passage which has a question and the context. You have to generate an answer to the question based on the information present in the context.
question:
Context: Emphysema, especially in the upper lobes, is frequently observed in association with idiopathic pulmonary fibrosis (IPF). However, the combination of emphysema plus IPF has received little attention.', 'To investigate the additional functional impairment from emphysema in IPF patients.', 'Twenty-one patients (mean age 66 y, 20 men) (Group I) who had both IPF (mean 35% of total lung volume) and emphysema (mean 14% of total lung volume) were compared to a group of 21 subjects who had IPF but no emphysema (Group II). The groups were matched for (among other criteria) the total extent of disease. Pulmonary function tests, Medical Research Council dyspnea score, 6-min walk test, and radiographic extents of both IPF and emphysema were obtained for each patient. The Composite Physiologic Index was calculated. In the total population (n = 42), the independent contributions of IPF and emphysema to several physiologic variables were investigated by using stepwise multiple regression analysis.', 'Despite the limited extent of emphysema, Groups I and II had similar physiologic impairment. Only residual volume and total lung capacity were significantly higher in Group I. According to stepwise multiple regression analysis, the extent of IPF and either the presence or the extent of emphysema in the total population were independent and significant predictors of dyspnea score, 6-min walk test, P(aO2), forced expiratory volume in the first second (FEV(1)), forced vital capacity (FVC), FEV1/FVC, the diffusing capacity of the lung for carbon monoxide, carbon monoxide diffusing capacity adjusted for alveolar volume (gas-transfer coefficient), and residual volume. The Composite Physiologic Index was closely related to the extent of IPF (r = 0.65, p < 0.0001) and to the dyspnea score (rho = 0.59, p < 0.0001).\Question: Does the presence of emphysema further impair physiologic function in patients with idiopathic pulmonary fibrosis?
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In former smokers with IPF, the presence and the extent of emphysema have a profound influence on physiologic function in terms of both further impairment and confounding effects.


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Context: Non-viral gene transfer efficiency is low as compared to viral vector systems. Here we describe the discovery of new drugs that are capable of enhancing non-viral gene transfer into mammalian cells using a novel two-stage screening procedure.', 'First, potential candidates are preselected from a molecular library at various concentrations by a semi-automated yeast transfection screen (YTS). The maximal transfection efficiency of every positive drug is subsequently determined in independent experiments at the optimal concentration and compared to the inhibitory effect of the drug on cell growth (IC50). In a subsequent mammalian cell transfection screen (MTS), the maximal transfection efficiency and the IC50 are determined for all preselected drugs using a human cell line and a luciferase reporter gene construct.', 'Employing our novel system we have been able to identify a new class of transfection enhancers, the tricyclic antidepressants (i.e. doxepin, maprotiline, desipramine and amoxapine). All positive drugs enhanced gene transfer in both yeast and human cell lines, but lower concentrations were sufficient for mammalian cells. With a triple combination of doxepin, amoxapine and chloroquine we obtained a transfection efficiency that exceeded that of chloroquine, one of the best-known transfection enhancers of mammalian cells, by nearly one order of magnitude.\Question: Does novel two-stage screening procedure lead to the identification of a new class of transfection enhancers?
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Non-viral gene transfer efficiency can be increased significantly using new transfection enhancers that are identified by a novel, semi-automated two-stage screening system employing yeast cells in the first and specific human target cells in the second round.


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Context: Insight into clinical response to platinum-based chemotherapy (PBC) in non-small-cell lung cancer (NSCLC).', 'Matched tumor and nontumor lung tissues from PBC-treated NSCLC patients (four nonresponders and four responders) and tumor tissue from an independent test set (four nonresponders and four responders), were profiled using microarrays. Lysosomal protease inhibitors SerpinB3 and cystatin C were highly correlated with clinical response and were further evaluated by immunohistochemistry in PBC-treated patients (36 prechemotherapy and 13 postchemotherapy). Investigation of the pathogenic and prognostic significance of SerpinB3 was performed in 251 primary tumors, with 64 regional lymph node pairs, from chemotherapy-naïve NSCLC patients using immunohistochemistry.', 'Bioinformatic analyses of gene expression in the training set identified a gene set (n = 17) that separated all patients in the training and test sets (n = 16) according to response in hierarchical clustering. Transcriptome profiling revealed that SerpinB3 mRNA was highly correlated with degree of response (r = -0.978; P < .0001) and was a clear outlier (nonresponders:responders > 50-fold). SerpinB3 protein expression was correlated with clinical response in PBC-treated NSCLC patients (P = .045). Expression of SerpinB3 and cystatin C, relative to the target, protease cathepsin B, was independently predictive of response (odds ratio, 17.8; 95% CI, 2.0 to 162.4; P = .01), with an accuracy of 72%. High SerpinB3 expression levels, invariably associated with chemoresistance, had contrasting prognostic impact in untreated squamous cell carcinomas (hazard ratio [HR], 0.43; 95% CI, 0.18 to 0.93) or adenocarcinomas (HR, 2.09; 95% CI, 1.03 to 4.72).\Question: Does tumor transcriptome reveal the predictive and prognostic impact of lysosomal protease inhibitors in non-small-cell lung cancer?
answer:

This provides the first comprehensive molecular characterization of clinical responsiveness to PBC in NSCLC and reveals the predictive and prognostic impact of two lysosomal protease inhibitors, potentially representing novel targets for NSCLC therapeutics.