Successful treatment of a high-risk nonseminomatous germ cell tumor using etoposide, methotrexate, actinomycin D, cyclophosphamide, and vincristine: A case report.

BACKGROUND: Choriocarcinoma is an infrequent entity and the most aggressive subtype of germ-cell tumors. Because of early metastatic spread and rapid disease progression, choriocarcinoma patients display poor prognosis. Although etoposide, methotrexate, actinomycin D, cyclophosphamide, and vincristine (EMA-CO) regimen is widely used to treat gestational trophoblastic tumors in females, its role in treating male choriocarcinoma is seldom reported. CASE SUMMARY: A 32-year-old man was diagnosed with burned-out primary germ cell tumors (GCT) with retroperitoneum, liver and lung metastases. Biopsy of the liver revealed pure choriocarcinoma. The patient received bleomycin, etoposide, and cisplatin chemotherapy. After two cycles of treatment, response evaluation revealed the mixed response. EMA-CO regimen was used in the second-line therapy. After eight cycles, the patient showed a potentially resectable state and thus, all residual masses were surgically removed. The patient was completely cured, and 10 years later, he is leading a healthy life without complications. CONCLUSION: This paper is the first case of high-risk nonseminomatous GCT in a male patient to be successfully treated with the EMA-CO regimen. The EMA-CO regimen can be used actively in patients with high-risk nonseminomatous GCT.

Detection of Chemical Warfare Agents by Colorimetric Sensor Arrays.

We report the successful use of colorimetric arrays to identify chemical warfare agents (CWAs). Methods were developed to interpret and analyze a 73-indicator array with an entirely automated workflow. Using a cross-validated first-nearest-neighbor algorithm for assessing detection and identification performances on 632 exposures, at 30 min postexposure we report, on average, 78% correct chemical identification, 86% correct class-level identification, and 96% correct red light/green light (agent versus non-agent) detection. Of 174 total independent agent test exposures, 164 were correctly identified from a 30 min exposure in the red light/green light context, yielding a 94% correct identification of CWAs. Of 149 independent non-agent exposures, 139 were correctly identified at 30 min in the red light/green light context, yielding a 7% false alarm rate. We find that this is a promising approach for the development of a miniaturized, field-portable analytical equipment suitable for soldiers and first responders.

Chemically Resistant Perfluoroalkoxy Nanoparticle-Packed Porous Substrates and Their Use in Colorimetric Sensor Arrays.

To create printing substrates for colorimetric sensor arrays, chemically resistant membranes are prepared by coating cellulose filter paper with perfluoroalkoxy (PFA) polymer nanoparticles. A water-based fluorothermoplastic polymer dispersion was diluted with an organic solvent that causes weak aggregation of polymer nanoparticles. The resulting solution improved adhesion between the polymer and the cellulose membrane, providing a more mechanically stable substrate. These PFA polymer-coated substrates demonstrated superior chemical resistance against strong alkalines and had relatively uniform nanoporous structures that substantially improved the printability of a colorimetric sensor array. Finally, colorimetric sensor arrays printed on these substrates were evaluated for the detection of four different toxic industrial chemicals (e.g., ammonia, hydrogen sulfide, nitrogen dioxide, and sulfur dioxide) at or below their permissible exposure limits.

The combined rapid detection and species-level identification of yeasts in simulated blood culture using a colorimetric sensor array.

BACKGROUND: A colorimetric sensor array (CSA) has been demonstrated to rapidly detect and identify bacteria growing in blood cultures by obtaining a species-specific "fingerprint" of the volatile organic compounds (VOCs) produced during growth. This capability has been demonstrated in prokaryotes, but has not been reported for eukaryotic cells growing in culture. The purpose of this study was to explore if a disposable CSA could differentially identify 7 species of pathogenic yeasts growing in blood culture. METHODS: Culture trials of whole blood inoculated with a panel of clinically important pathogenic yeasts at four different microorganism loads were performed. Cultures were done in both standard BacT/Alert and CSA-embedded bottles, after adding 10 mL of spiked blood to each bottle. Color changes in the CSA were captured as images by an optical scanner at defined time intervals. The captured images were analyzed to identify the yeast species. Time to detection by the CSA was compared to that in the BacT/Alert system. RESULTS: One hundred sixty-two yeast culture trials were performed, including strains of several species of Candida (Ca. albicans, Ca. glabrata, Ca. parapsilosis, and Ca. tropicalis), Clavispora (synonym Candida) lusitaniae, Pichia kudriavzevii (synonym Candida krusei) and Cryptococcus neoformans, at loads of 8.2 × 105, 8.3 × 103, 8.5 × 101, and 1.7 CFU/mL. In addition, 8 negative trials (no yeast) were conducted. All negative trials were correctly identified as negative, and all positive trials were detected. Colorimetric responses were species-specific and did not vary by inoculum load over the 500000-fold range of loads tested, allowing for accurate species-level identification. The mean sensitivity for species-level identification by CSA was 74% at detection, and increased with time, reaching almost 95% at 4 hours after detection. At an inoculum load of 1.7 CFU/mL, mean time to detection with the CSA was 6.8 hours (17%) less than with the BacT/Alert platform. CONCLUSION: The CSA combined rapid detection of pathogenic yeasts in blood culture with accurate species-level identification.

Disposable microfluidic sensor arrays for discrimination of antioxidants.

A microfluidic colorimetric sensor array was developed for detection and identification of various antioxidants. The sensor was fabricated by a photolithographic method, and consists of an array of printed cross-responsive indicators. The microfluidic design also incorporates pre-activation spots to allow printing of chemically incompatible components separately. Separately printed oxidizer allowed an oxidation of adjacent redox indicators only when aqueous sample was added to the sensor cartridge. Antioxidants were primarily detected by measuring the extent of inhibition of this oxidation reaction. Using this flow-based technique, a clear differentiation of 8 different antioxidants and 4 different teas has been demonstrated with 98.5% sensitivity.

Bacterial culture detection and identification in blood agar plates with an optoelectronic nose.

Clinical microbiology automation is currently limited by the lack of an in-plate culture identification system. Using an inexpensive, printed, disposable colorimetric sensor array (CSA) responsive to the volatiles emitted into plate headspace by microorganisms during growth, we report here that not only the presence but the species of bacteria growing in plate was identified before colonies are visible. In 1894 trials, 15 pathogenic bacterial species cultured on blood agar were identified with 91.0% sensitivity and 99.4% specificity within 3 hours of detection. The results indicate CSAs integrated into Petri dish lids present a novel paradigm to speciate microorganisms, well-suited to integration into automated plate handling systems.

Rapid Diagnosis of Tuberculosis from Analysis of Urine Volatile Organic Compounds.

The World Health Organization has called for simple, sensitive, and non-sputum diagnostics for tuberculosis. We report development of a urine tuberculosis test using a colorimetric sensor array (CSA). The sensor comprised of 73 different indicators captures high-dimensional, spatiotemporal signatures of volatile chemicals emitted by human urine samples. The sensor responses to 63 urine samples collected from 22 tuberculosis cases and 41 symptomatic controls were measured under five different urine test conditions. Basified testing condition yielded the best accuracy with 85.5% sensitivity and 79.5% specificity. The CSA urine assay offers desired features needed for tuberculosis diagnosis in endemic settings.

Detecting cancer by breath volatile organic compound analysis: a review of array-based sensors.

Cancer diagnosis is typically delayed to the late stages of disease due to the asymptomatic nature of cancer in its early stages. Cancer screening offers the promise of early cancer detection, but most conventional diagnostic methods are invasive and remain ineffective at early detection. Breath analysis is, however, non-invasive and has the potential to detect cancer at an earlier stage by analyzing volatile biomarkers in exhaled breath. This paper summarizes breath sampling techniques and recent developments of various array-based sensor technologies for breath analysis. Significant advancements were made by a number of different research groups in the development of nanomaterial-based sensor arrays, and the ability to accurately distinguish cancer patients from healthy controls based on the volatile organic compounds (VOCs) in exhaled breath has been demonstrated. Optical sensors based on colorimetric sensor array technology are also discussed, where preliminary clinical studies suggest that metabolic VOC profiles could be used to accurately diagnose various forms of lung cancer. Recent studies have demonstrated the potential of using metabolic VOCs for cancer detection, but further standardization and validation is needed before breath analysis can be widely adopted as a clinically useful tool.

Colorimetric sensor array allows fast detection and simultaneous identification of sepsis-causing bacteria in spiked blood culture.

Sepsis is a medical emergency demanding early diagnosis and tailored antimicrobial therapy. Every hour of delay in initiating effective therapy measurably increases patient mortality. Blood culture is currently the reference standard for detecting bloodstream infection, a multistep process which may take one to several days. Here, we report a novel paradigm for earlier detection and the simultaneous identification of pathogens in spiked blood cultures by means of a metabolomic "fingerprint" of the volatile mixture outgassed by the organisms. The colorimetric sensor array provided significantly faster detection of positive blood cultures than a conventional blood culture system (12.1 h versus 14.9 h, P < 0.001) while allowing for the identification of 18 bacterial species with 91.9% overall accuracy within 2 h of growth detection. The colorimetric sensor array also allowed for discrimination between unrelated strains of methicillin-resistant Staphylococcus aureus, indicating that the metabolomic fingerprint has the potential to track nosocomial transmissions. Altogether, the colorimetric sensor array is a promising tool that offers a new paradigm for diagnosing bloodstream infections.

The use of colorimetric sensor arrays to discriminate between pathogenic bacteria.

A colorimetric sensor array is a high-dimensional chemical sensor that is cheap, compact, disposable, robust, and easy to operate, making it a good candidate technology to detect pathogenic bacteria, especially potential bioterrorism agents like Yersinia pestis and Bacillus anthracis which feature on the Center for Disease Control and Prevention's list of potential biothreats. Here, a colorimetric sensor array was used to continuously monitor the volatile metabolites released by bacteria in solid media culture in an Advisory Committee on Dangerous Pathogen Containment Level 3 laboratory. At inoculum concentrations as low as 8 colony-forming units per plate, 4 different bacterial species were identified with 100% accuracy using logistic regression to classify the kinetic profile of sensor responses to culture headspace gas. The sensor array was able to further discriminate between different strains of the same species, including 5 strains of Yersinia pestis and Bacillus anthracis. These preliminary results suggest that disposable colorimetric sensor arrays can be an effective, low-cost tool to identify pathogenic bacteria.

Luteolin suppresses UVB-induced photoageing by targeting JNK1 and p90 RSK2.

Multiple lines of evidence suggest that natural compounds can prevent skin ageing induced by ultraviolet light. Luteolin, a bioactive compound found in chilli, onion, broccoli, celery and carrot, has been reported to exhibit anti-photoageing effects in vitro. However, the molecular targets and mechanisms of luteolin are still poorly understood. In this study, we sought to investigate the effects of luteolin on UVB-induced photoageing and the molecular mechanisms involved, using HaCaT human keratinocytes and SKH-1 hairless mice. Luteolin was found to inhibit UVB-induced MMP-1 expression in HaCaT cells, as well as UVB-induced activation of AP-1, a well-known transcription factor targeting the MMP-1 promoter region, as well as c-Fos and c-Jun, which comprise the AP-1 complex. In contrast, Western blot data showed that UVB-induced phosphorylation of JNK, ERK and p90RSK was not inhibited by luteolin. In vitro kinase assay data revealed that luteolin significantly suppressed JNK1 and p90RSK activity, but not that of JNK2 and ERK2. Pull-down assays showed that luteolin binds JNK1 in an ATP-competitive manner and p90RSK2 in an ATP-independent manner. Luteolin also inhibited UVB-induced wrinkle formation and MMP-13 expression, a rodent interstitial collagenase in mouse skin, in vivo. Taken together, our observations suggest that luteolin exhibits anti-photoageing effects in vitro and in vivo and may have potential as a treatment for the prevention of skin ageing.

Colorimetric sensor array for determination and identification of toxic industrial chemicals.

A low-cost yet highly sensitive colorimetric sensor array for the detection and identification of toxic industrial chemicals (TICs) has been developed. The sensor consists of a disposable array of cross-responsive nanoporous pigments whose colors are changed by diverse chemical interactions with analytes. Clear differentiation among 20 different TICs has been easily achieved at both their IDLH (immediately dangerous to life or health) concentration within 2 min of exposure and PEL (permissible exposure limit) concentration within 5 min of exposure with no errors or misclassifications. Detection limits are generally well below the PEL (in most cases below 5% of PEL) and are typically in the low ppb range. The colorimetric sensor array is not responsive to changes in humidity or temperature over a substantial range. The printed arrays show excellent batch to batch reproducibility and long shelf life (greater than 3 months).

A colorimetric sensor array for identification of toxic gases below permissible exposure limits.

A colorimetric sensor array has been developed for the rapid and sensitive detection of 20 toxic industrial chemicals (TICs) at their PELs (permissible exposure limits). The color changes in an array of chemically responsive nanoporous pigments provide facile identification of the TICs with an error rate below 0.7%.

A colorimetric sensor array of porous pigments.

The development of a low-cost, simple colorimetric sensor array capable of the detection and identification of toxic gases is reported. This technology uses a disposable printed array of porous pigments in which metalloporphyrins and chemically-responsive dyes are immobilized in a porous matrix of organically modified siloxanes (ormosils) and printed on a porous membrane. The printing of the ormosil into the membrane is highly uniform and does not lessen the porosity of the membrane, as shown by scanning electron microscopy. When exposed to an analyte, these pigments undergo reactions that result in well-defined color changes due to strong chemical interactions: ligation to metal ions, Lewis or Brønsted acid-base interactions, hydrogen bonding, etc. Striking visual identification of 3 toxic gases has been shown at the IDLH (immediately dangerous to life and health) concentration, at the PEL (permissible exposure level), and at a level well below the PEL. Identification and quantification of analytes were achieved using the color change profiles, which were readily distinguishable in a hierarchical clustering analysis (HCA) dendrogram, with no misclassifications in 50 trials.

An optoelectronic nose for the detection of toxic gases.

We have developed a simple colorimetric sensor array that detects a wide range of volatile analytes and then applied it to the detection of toxic gases. The sensor consists of a disposable array of cross-responsive nanoporous pigments with colours that are changed by diverse chemical interactions with analytes. Although no single chemically responsive pigment is specific for any one analyte, the pattern of colour change for the array is a unique molecular fingerprint. Clear differentiation among 19 different toxic industrial chemicals (TICs) within two minutes of exposure at concentrations immediately dangerous to life or health were demonstrated. Based on the colour change of the array, quantification of each analyte was accomplished easily, and excellent detection limits were achieved, generally below the permissible exposure limits. Different TICs were identified readily using a standard chemometric approach (hierarchical clustering analysis), with no misclassifications over 140 trials.

Colorimetric detection and identification of natural and artificial sweeteners.

A disposable, low-cost colorimetric sensor array has been created by pin-printing onto a hydrophilic membrane 16 chemically responsive nanoporous pigments that are comprised of indicators immobilized in an organically modified silane (ormosil). The array has been used to detect and identify 14 different natural and artificial sweeteners at millimolar concentrations, as well as commonly used individual-serving sweetener packets. The array has shown excellent reproducibility and long shelf life and has been optimized to work in the biological pH regime.

Chemically responsive nanoporous pigments: colorimetric sensor arrays and the identification of aliphatic amines.

A general method has been developed for the preparation of microspheres of nanoporous pigments, their formulation into chemically responsive pigment inks, and the printing of these inks as colorimetric sensor arrays. Using an ultrasonic-spray aerosol-gel synthesis from chemically responsive dyes and common silica precursors, 16 different nanoporous pigment microspheres have been prepared and characterized. New colorimetric sensor arrays have been created by printing inks of these chemically responsive pigments as primary sensor elements; these arrays have been successfully tested for the detection, identification, and quantitation of toxic aliphatic amines. Among 11 structurally similar amines, complete identification of each analyte without confusion was achieved using hierarchical cluster analysis (HCA). Furthermore, visual identification of ammonia gas was easily made at the IDLH (immediately dangerous to life or health), PEL (permissible exposure limits), and 0.1 PEL concentrations with high reproducibility.

A colorimetric sensor array for detection and identification of sugars.

Molecular recognition of sugars and a practical method to detect and discriminate among a large number of such similar analytes remain substantial scientific challenges. We report here a low-cost, simple colorimetric sensor array capable of identification and quantification of sugars and related compounds. Fifteen different monosaccharides, disaccharides, and artificial sweeteners were differentiated without error in 80 trials. Limits of detection at pH 7.4 for glucose were <1 mM, which is below physiologically important levels.

Kinetic resolution of racemic lactones by conjugate additions of allylic organolithium species: direct formation of three contiguous centers with high diastereo- and enantioselectivities.

[reaction: see text] Kinetic resolution of racemic alpha,beta-unsaturated lactones by the organolithium species produced from asymmetric lithiation of N-Boc-N-(p-methoxyphenyl)cinnamylamine provides conjugate addition products with three contiguous stereogenic centers in yields of 62-77% with diastereomeric ratios from 75:25 to >99:1 and enantiomeric ratios for the major diastereomers from 94:6 to 98:2.