silicon and Lung-Neoplasms

Despite the knowledge of the link between many sites of cancer occurence and previous occupational exposure, occupational cancers are generally underestimated. These cancers can be prevented through specific plans. In France, the number of cases requesting and receiving compensation for occupational cancer is increasing. The frequency of occupational exposure to carcinogens was recently evaluated. Legislation was reinforced in order to obtain a better control of exposure to carcinogens in the workplace. Lung cancer is the most frequent of occupational cancers. Epidemiological studies contribute to a better knowledge of etiologies and occupations responsible for the outcome of these cancers and allow quantification of the risk of cancer linked to different situations of exposure. Beside classical epidemiological studies, molecular epidemiology aims at identifying molecular targets of occupational agents. This approach may allow a better knowledge of the part played by occupational agents in these multifactorial diseases.

Topics: Electromagnetic Fields; France; Humans; Lung Neoplasms; Mineral Fibers; Neoplasms; Occupational Diseases; Occupational Exposure; Occupational Health; Occupations; Risk Factors; Silicon

Approximately three million workers in the United States are estimated to be exposed to silica, man-made mineral fibers, and asbestos. The lung is the primary target organ of concern. Each of these substances is composed predominantly of silicon and oxygen; asbestos and silica are crystalline, and asbestos and man-made mineral fibers are fibers. Man-made mineral fibers and asbestos are used as insulating agents, with the former having generally replaced the latter in recent years. Silica is used in foundries, pottery, and brick making, and is encountered by miners. A meta-analysis of 16 of the largest studies with well-documented silica exposure and low probability of confounding by other occupational exposures, indicates a relative risk (RR) of 1.3 (95 percent confidence interval [CI] = 1.2-1.4). Lung cancer risks are highest and most consistent for silicotics, who have received the highest doses (RR = 2.3, CI = 2.2-2.4, across 19 studies). The data for mineral fibers continue to support the International Association for Research on Cancer's 1988 judgment that mineral fibers are a possible human carcinogen (Group 2B). Recent epidemiologic studies provide little evidence for lung carcinogenicity for either glass wool or rock/slag wool. Ceramic fibers, a much less common exposure than glass wool and rock/slag wool, are of concern because of positive animal studies, but there are insufficient human data. Regarding asbestos, its carcinogenicity for the lung and mesothelium is well established. With regard to the controversy over chrysotile and mesothelioma, the data suggest chrysotile does cause mesothelioma, although it may be less potent than amphibole asbestos.

Topics: Animals; Asbestos; Asbestos, Serpentine; Carcinogens; Ceramics; Confidence Intervals; Confounding Factors, Epidemiologic; Construction Materials; Crystallization; Disease Models, Animal; Glass; Humans; Lung Neoplasms; Mesothelioma; Meta-Analysis as Topic; Mineral Fibers; Mining; Occupational Diseases; Occupational Exposure; Oxygen; Probability; Risk Factors; Silicon; Silicon Dioxide; Silicosis; United States

This paper reports on pulmonary dust retention in a man who worked 42 years in the vicinity of an Acheson furnace of a silicon carbide plant and had a carborundum pneumoconiosis. Special attention is paid to the retained silicon carbide fibers in the lung parenchyma. The concentration of silicon carbide fibers longer than 5 microns is 39,300 fibers/mg dry lung. These fibers have a similar morphology to fibers observed in the working environment. The result is compared to pulmonary retention of workers exposed to asbestos.

Topics: Carbon; Carbon Compounds, Inorganic; Carcinoma, Squamous Cell; Humans; Lung Neoplasms; Male; Microscopy, Electron, Scanning Transmission; Occupations; Pneumoconiosis; Pneumonectomy; Silicon; Silicon Compounds

Consideration of the human epidemiology of diseases arising from exposure to naturally occurring and man-made mineral fibers encompasses the several forms of asbestos (chrysotile, crocidolite, amosite, anthophyllite, tremolite-actinolite), other naturally occurring silicates (talc, sepiolite, erionite, attapulgite, vermiculite, and wollastonite), and man-made mineral fibers (glass continuous filament, glass/rock/slag insulation wools, ceramic and other refractory fibers, and glass microfibers). The diseases arising from exposures to some of these fibers include pleural thickening (plaques, diffuse pleural thickening, and calcification), pulmonary fibrosis, lung cancers, mesothelioma of the pleura and peritoneum, and other cancers). Risk factors important in assessing these diseases include assessment of latency, duration of exposure, cumulative exposure, fiber origin and characteristics (length and diameter), other possible confounding occupational or environmental exposures, and smoking. Methodological issues commonly presenting problems in evaluation of these data include assessment of the adequacy of environmental exposures, particularly in regard to fiber identification, distribution, and concentration over the duration of exposure, and the adequacy of study design to detect health effects (disease frequency, latency, and cohort size). Research priorities include further assessment and standardization of pleural thickening relative to fiber exposure, uniform mesothelioma surveillance, further epidemiological assessment of certain silicate and man-made mineral fiber cohorts with emphasis given to assessment of tremolite and small diameter glass and ceramic fibers. Further assessment of possible health risks of the general public should await improved definition of relevant fiber exposure in ambient air.

Topics: Asbestos; Asbestosis; Humans; Lung Neoplasms; Mesothelioma; Minerals; Neoplasms; Pleural Diseases; Respiratory Tract Diseases; Silicon

Drug-resistant capacity in a small population of tumor-initiating cancer stem cells (tiCSCs) can be due to aberrant epigenetic changes. However, currently available conventional detection methods are inappropriate and cannot be applied to investigate the scarce population (tiCSCs). In addition, selective inhibitor drugs are shown to reverse epigenetic changes; however, each cancer type is discrete. Hence, it is essential to probe the resultant changes in tiCSCs even after therapy. Therefore, we have developed a multimode nanoplatform to investigate tiCSCs, detect epigenetic changes, and subsequently explore their transformation signals following drug therapy. We performed this by developing a surface-enhanced Raman scattering (SERS)-active nanoplatform integrated with n-dopant using an ultrafast laser ionization technique. The dopant functionalization enhances Raman scattering ability and permits label-free analysis of biomarkers in tiCSCs with the resolution down to the cellular level. Here, we investigated epigenetic biomarkers of tiCSCs in pancreatic and lung cancers. An extended study using inhibitor drugs demonstrates an unexpected increase of tiCSCs from lung cancer; this difference can be attributed to transformation changes in lung tiCSC. Thus, our work brings new insight into the differentiation abilities of CSCs upon epigenetic reversal, emphasizing unique perceptions in cancer treatment.

Topics: Biomarkers, Tumor; Cell Cycle Checkpoints; Cell Line, Tumor; Decitabine; Epigenesis, Genetic; Humans; Hydroxamic Acids; Lasers; Lung Neoplasms; Nanostructures; Neoplastic Stem Cells; Pancreatic Neoplasms; Phosphorus; Silicon; Spectrum Analysis, Raman

Rapid identification of lung-cancer micro-lesions is becoming increasingly important to improve the outcome of surgery by accurately defining the tumor/normal tissue margins and detecting tiny tumors, especially for patients with low lung function and early-stage cancer. The purpose of this study is to select and validate the best red fluorescent probe for rapid diagnosis of lung cancer by screening a library of 400 red fluorescent probes based on 2-methyl silicon rhodamine (2MeSiR) as the fluorescent scaffold, as well as to identify the target enzymes that activate the selected probe, and to confirm their expression in cancer cells. The selected probe, glutamine-alanine-2-methyl silicon rhodamine (QA-2MeSiR), showed 96.3% sensitivity and 85.2% specificity for visualization of lung cancer in surgically resected specimens within 10 min. In order to further reduce the background fluorescence while retaining the same side-chain structure, we modified QA-2MeSiR to obtain glutamine-alanine-2-methoxy silicon rhodamine (QA-2OMeSiR). This probe rapidly visualized even borderline lesions. Dipeptidyl peptidase 4 and puromycin-sensitive aminopeptidase were identified as enzymes mediating the cleavage and consequent fluorescence activation of QA-2OMeSiR, and it was confirmed that both enzymes are expressed in lung cancer. QA-2OMeSiR is a promising candidate for clinical application.

Topics: Alanine; Aminopeptidases; Dipeptidyl Peptidase 4; Fluorescent Dyes; Glutamine; Humans; Lung Neoplasms; Rhodamines; Silicon

Although immune checkpoint inhibitors (ICIs) have been widely applied to treat non-small cell lung cancer (NSCLC), a significant proportion of patients, especially those with spinal metastasis (NSCLC-SM), are insensitive to anti-programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) ICIs. A drug delivery nano-controller of PD-L1 that targets NSCLC-SM can solve this problem, however, none have been developed to date. In this study, it is shown that integrin β3 (β3-int) is strongly upregulated in NSCLC-SM. Its inhibitor RGDyK promotes PD-L1 ubiquitination, indicating the potential application of RGDyK as a new PD-L1 inhibitor in nano-controller and a targeting peptide for NSCLC-SM treatment. According to the synergistic effect of photodynamic therapy and ICIs on T-cell activation through the release of tumor antigens, RGDyK-modified and zinc protoporphyrin (ZnPP)-loaded mesoporous silicon nanoparticles (ZnPP@MSN-RGDyK) are fabricated. The ZnPP@MSN-RGDyK nanoparticles precisely target β3-int to inhibit PD-L1, exhibiting high photodynamic therapy efficiency, and excellent immunotherapeutic effects in an NSCLC-SM mouse model. Collectively, the findings indicate that ZnPP@MSN-RGDyK is a promising immunotherapeutic agent for treating NSCLC-SM.

Topics: Animals; Antigens, Neoplasm; B7-H1 Antigen; Carcinoma, Non-Small-Cell Lung; Immune Checkpoint Inhibitors; Immunotherapy; Integrin beta3; Lung Neoplasms; Mice; Programmed Cell Death 1 Receptor; Silicon; Spinal Neoplasms

The rapid diagnosis of cancer, especially in its early stages, is crucial for on-time medical treatment and for increasing the patient survival rate. Lung cancer shows the highest mortality rate and the lowest 5-year survival rate due to the late diagnosis in advanced cancer stages. Providing rapid and reliable diagnostic tools is a top priority to address the problem of a delayed cancer diagnosis. We introduce a nanophotonic biosensor for the direct and real-time detection in human plasma of the microRNA-21-5p biomarker related to lung cancer. The biosensor employs a silicon photonic bimodal interferometric waveguide that provides a highly sensitive detection in a label-free format. We demonstrate a very competitive detectability for direct microRNA-21-5p biomarker assays in human plasma samples (estimated LOD: 25 pM). The diagnostic capability of our biosensor was validated by analyzing 40 clinical samples from healthy individuals and lung cancer patients, previously analyzed by reverse-transcription quantitative polymerase chain reaction (qRT-PCR). We could successfully identify and quantify the levels of microRNA in a one-step assay, without the need for DNA extraction or amplification steps. The study confirmed the significance of implementing this biosensor technique compared to the benchmarking molecular analysis and showed excellent agreement with previous results employing the traditional qRT-PCR. This work opens new possibilities for the true implementation of point-of-care biosensors that enable fast, simple, and efficient early diagnosis of cancer diseases.

Topics: Biosensing Techniques; DNA; Humans; Lung Neoplasms; MicroRNAs; Silicon

In this paper, we demonstrate an innovative electromagnetic targeting system utilizing a passive magnetic-flux-concentrator for tracking endobronchoscope used in the diagnosis process of lung cancer tumors/lesions. The system consists of a magnetic-flux emitting coil, a magnetic-flux receiving electromagnets-array, and high permeability silicon-steel sheets rolled as a collar (as the passive magnetic-flux-concentrator) fixed in a guide sheath of an endobronchoscope. The emitting coil is used to produce AC magnetic-flux, which is consequently received by the receiving electromagnets-array. Due to the electromagnetic-induction, a voltage is induced in the receiving electromagnets-array. When the endobronchoscope's guide sheath (with the silicon-steel collar) travels between the emitting coil and the receiving electromagnets-arrays, the magnetic flux is concentrated by the silicon-steel collar and thereby the induced voltage is changed. Through analyzing the voltage-pattern change, the location of the silicon-steel collar with the guide sheath is targeted. For testing, a bronchial-tree model for training medical doctors and operators is used to test our system. According to experimental results, the system is successfully verified to be able to target the endobronchoscope in the bronchial-tree model. The targeting errors on the

Topics: Bronchoscopy; Electromagnetic Phenomena; Humans; Lung Neoplasms; Silicon; Steel

The inability of traditional chemotherapeutics to reach cancer tissue reduces the treatment efficacy and leads to adverse effects. A multifunctional nanovector was developed consisting of porous silicon, superparamagnetic iron oxide, calcium carbonate, doxorubicin and polyethylene glycol. The particles integrate magnetic properties with the capacity to retain drug molecules inside the pore matrix at neutral pH to facilitate drug delivery to tumor tissues. The MRI applicability and pH controlled drug release were examined in vitro together with in-depth material characterization. The in vivo biodistribution and compound safety were verified using A549 lung cancer bearing mice before proceeding to therapeutic experiments using CT26 cancer implanted mice. Loading doxorubicin into the porous nanoparticle negated the adverse side effects encountered after intravenous administration highlighting the particles' excellent biocompatibility. Furthermore, the multifunctional nanovector induced 77% tumor reduction after intratumoral injection. The anti-tumor effect was comparable with that of free doxorubicin but with significantly alleviated unwanted effects. These results demonstrate that the developed porous silicon-based nanoparticles represent promising multifunctional drug delivery vectors for cancer monitoring and therapy.

Topics: A549 Cells; Animals; Antibiotics, Antineoplastic; Chemistry, Pharmaceutical; Colonic Neoplasms; Delayed-Action Preparations; Doxorubicin; Drug Delivery Systems; Drug Liberation; Excipients; Humans; Lung Neoplasms; Magnetic Resonance Imaging; Male; Mice; Mice, Inbred NOD; Mice, SCID; Nanoparticles; Porosity; Silicon; Tissue Distribution

Tumor-derived extracellular vesicles (EVs) present in bodily fluids are emerging liquid biopsy markers for non-invasive cancer diagnosis and treatment monitoring. Because the majority of EVs in circulation are not of tumor origin, it is critical to develop new platforms capable of enriching tumor-derived EVs from the blood. Herein, we introduce a biostructure-inspired NanoVilli Chip, capable of highly efficient and reproducible immunoaffinity capture of tumor-derived EVs from blood plasma samples. Anti-EpCAM-grafted silicon nanowire arrays were engineered to mimic the distinctive structures of intestinal microvilli, dramatically increasing surface area and enhancing tumor-derived EV capture. RNA in the captured EVs can be recovered for downstream molecular analyses by reverse transcription Droplet Digital PCR. We demonstrate that this assay can be applied to monitor the dynamic changes of ROS1 rearrangements and epidermal growth factor receptor T790M mutations that predict treatment responses and disease progression in non-small cell lung cancer patients.

Topics: Adult; Aged; Antibodies, Immobilized; Biomarkers, Tumor; Carcinoma, Non-Small-Cell Lung; Epithelial Cell Adhesion Molecule; ErbB Receptors; Extracellular Vesicles; Female; Gene Rearrangement; Humans; Lung Neoplasms; Male; Middle Aged; Nanowires; Polymerase Chain Reaction; Polymorphism, Single Nucleotide; Protein-Tyrosine Kinases; Proto-Oncogene Proteins; RNA, Messenger; Silicon

Malignant central airway obstruction around the main carina often requires placement of Y‑shaped stents. In this study, we aimed to determine the safety of silicone Y stents placed around the main carina in the malignant airway obstruction by examining the long term complications, emergence times and treatment approaches of complications.. Between May 2012 and July 2015, 47 silicone Y stents were placed in 46 patients with malignant external compression or mixed type stenosis around the main carina. Patient stents were placed via rigid bronchoscopy under total intravenous anesthesia in operating room conditions.. In the half of the patients (23/46), stents were placed under urgent conditions due to acute respiratory failure. Stents were deployed successfully in all the patients. No procedure related deaths were observed. The median time of survival following stent insertion was 157 days. The total long-term complication rate of silicone Y stents was 28.3%. Mucostasis (8.7%) and migration (2.2%) were observed within the first month after placement of the silicone Y stents (median 18 days), stent-edge granulation tissue development (13.0%) was observed at the earliest one month (median 64, range 34-386 days) and stent-edge tumor tissue development (4.3%) were observed at the earliest 3 months (median 151, range 85-217 days). A total of 7 (15.2%) stents were removed, 2 of which were due to mucostasis and 5 of which were due to granulation tissue development. One patient's stent was replaced with a longer silicone Y stent due to stent-edge tumor tissue development.. The best palliative treatment of malignant tumor stenosis around the main carina is still silicone Y stent placement, but the long-term complication rate can be high. For this group of patients, bronchoscopy to be performed at the first and third months after silicone Y stent placement may provide early detection of stent-edge tissue development.

Topics: Adult; Aged; Aged, 80 and over; Airway Obstruction; Bronchography; Bronchoscopy; Carcinoma, Squamous Cell; Constriction, Pathologic; Female; Humans; Lung Neoplasms; Male; Middle Aged; Prosthesis Failure; Retrospective Studies; Silicon; Silicones; Stents; Trachea; Treatment Outcome

For many normal and aberrant cell behaviours, it is important to understand the origin of cellular heterogeneity. Although powerful methods for studying cell heterogeneity have emerged, they are more suitable for common rather than rare cells. Exploring the heterogeneity of rare single cells is challenging because these rare cells must be first pre-concentrated and undergo analysis prior to classification and expansion. Here, a versatile capture & release platform consisting of an antibody-modified and electrochemically cleavable semiconducting silicon surface for release of individual cells of interest is presented. The captured cells can be interrogated microscopically and tested for drug responsiveness prior to release and recovery. The capture & release strategy was applied to identify rare tumour cells from whole blood, monitor the uptake of, and response to, doxorubicin and subsequently select cells for single-cell gene expression based on their response to the doxorubicin.

Topics: Animals; Cell Survival; Doxorubicin; Electrochemical Techniques; Female; HeLa Cells; Humans; Lung Neoplasms; MCF-7 Cells; Mice; Mice, Inbred BALB C; Mice, Nude; Microscopy, Fluorescence; Neoplasm Transplantation; Photochemistry; Silicon; Single-Cell Analysis

Mesothelioma is a malignant tumor mainly correlated to occupational asbestos exposure. Rare reports describe its occurrence also in animals, mainly linked to asbestos in the environment. Asbestos exposure is demonstrated by the appearance of characteristic histological hallmarks: asbestos containing ferruginous bodies that are iron-based structures forming around fibers and also other dust particles. Here we present a clinical case of a suspect of mesothelioma in the peritoneum of a dog with parallel histological observation of ferruginous bodies. To possibly correlate the dog tumor to environmental exposure, we performed X-ray fluorescence (XRF) analyses at two different synchrotrons to resolve the ferruginous bodies' composition. While the histological examination diagnoses a tubulo-papillary mesothelioma, the XRF analyses show that ferruginous bodies contain Si particles, resembling formations of exogenous origin; however, the morphology is unlikely that of asbestos fibers. We speculate that the peritoneal mesothelioma of this dog could be related to environmental exposure to non-asbestos material.

Topics: Animals; Asbestos; Dogs; Environmental Exposure; Immunohistochemistry; Iron; Lung; Lung Neoplasms; Male; Mesothelioma; Mesothelioma, Malignant; Peritoneal Neoplasms; Silicon; Spectrometry, X-Ray Emission; Synchrotrons

In this work, a real-time assay for highly sensitive, label-free, multiplexed electrical detection of lung cancer biomarkers was developed by using silicon nanowire field-effect (SiNW-FET) devices. Highly responsive SiNW arrays were fabricated using a CMOS-compatible anisotropic self-stop etching technique with mass reproducibility and low cost character. The SiNW nanosensor was integrated with PDMS microfluidic device, which allows rapid analyte delivery, makes the analysis to be conducted using exceedingly small samples and enables potential multiplexed detection. The nanowire arrays allowed highly selective and sensitive multiplexed detection of microRNA (miRNA)-126 and CEA. Due to high surface-to-volume ratio that the nanowire dimensions confer, the detection floor of single molecule was achieved. The potential utility in identifying clinical samples for early diagnosis of cancer was demonstrated by analyzing biomarkers in clinical related samples. The developed nanosensor with capability for multiplexed real-time monitoring of biomarkers with high sensitivity and selectivity in clinically relevant samples is highly attractive for diagnosis and treatment of cancer and other diseases.

Topics: Biomarkers, Tumor; Biosensing Techniques; Carcinoembryonic Antigen; Dimethylpolysiloxanes; Equipment Design; Humans; Lab-On-A-Chip Devices; Lung Neoplasms; MicroRNAs; Nanowires; Silicon

Collecting circulating tumor cells (CTCs) shed from solid tumor through a minimally invasive approach provides an opportunity to solve a long-standing oncology problem, the real-time monitoring of tumor state and analysis of tumor heterogeneity. However, efficient capture and detection of CTCs with diverse phenotypes is still challenging. In this work, a microfluidic assay is developed using the rationally-designed aptamer cocktails with synergistic effect. Enhanced and differential capture of CTCs for nonsmall cell lung cancer (NSCLC) patients is achieved. It is also demonstrated that the overall consideration of CTC counts obtained by multiple aptamer combinations can provide more comprehensive information in treatment monitoring.

Topics: Aptamers, Nucleotide; Cell Line, Tumor; Fluorescence; Humans; Lung Neoplasms; Microfluidics; Nanowires; Neoplastic Cells, Circulating; Reproducibility of Results; Silicon

One-lung ventilation is challenging in patients with difficult airway who require lung surgery. The choice of airway technique remains limited in patients with permanent tracheostomy after total laryngectomy. Conventional airway management techniques and available airway equipment have limited the options for securing airway in such patients, and dedicated airway equipment is not available for the management of such patients. Here, using endobronchial blocker through adult silicon hyperflex tracheostomy tube with an adjustable flange, we report a successful airway management for 1-lung ventilation in a patient with total laryngectomy with permanent tracheostomy.

Topics: Bronchoscopy; Female; Humans; Intubation, Intratracheal; Laryngectomy; Lung; Lung Neoplasms; Middle Aged; One-Lung Ventilation; Silicon; Tracheostomy

One critical functionality of the carrier system utilized in targeted drug delivery is its ability to trigger the release of the therapeutic cargo once the carrier has reached its target. External triggering is an alluring approach as it can be applied in a precise spatiotemporal manner. In the present study, we achieved external triggering through the porous silicon (PSi) nanoparticles (NPs) by providing a pulse of infrared or radiofrequency radiation. The NPs were grafted with a temperature responsive polymer whose critical temperature was tailored to be slightly above 37°C. The polymer coating improved the biocompatibility of the NPs significantly in comparison with their uncoated counterparts. Radiation induced a rapid temperature rise, which resulted in the collapse of the polymer chains facilitating the cargo release. Both infrared and radiofrequency radiation were able to efficiently trigger the release of the encapsulated drug in vitro and induce significant cell death in comparison to the control groups. Radiofrequency radiation was found to be more efficient in vitro, and the treatment efficacy was verified in vivo in a lung carcinoma (3LL) mice model. After a single intratumoral administration of the carrier system combined with radiofrequency radiation, there was clear suppression of the growth of the carcinoma and a prolongation of the survival time of the animals.. The temperature responsive (TR) polymer grafted on the surface of porous silicon nanoparticles (PSi NPs) changes its conformation in response to the heating induced by infrared or radiofrequency radiation. The conformation change allows the loaded doxorubicin to escape from the pores, achieving controlled drug release from TR PSi NPs, which displayed efficacy against malignant cells both in vitro and in vivo.

Topics: Acrylic Resins; Animals; Antineoplastic Agents; Cell Line, Tumor; Drug Carriers; Drug Liberation; Humans; Hypothermia, Induced; Infrared Rays; Lung Neoplasms; Male; Mice, Inbred CBA; Nanoparticles; Neoplasm Transplantation; Porosity; Pulsed Radiofrequency Treatment; Silicon; Surface Properties

We developed a silicon nanowire based electrical cell impedance sensor (SiNW-ECIS) as an instrument that detects cancerous cultured living lung cells by monitoring their spreading state at which the cells stretched and become extended on nanowires. Further current penetration into the extended membrane of malignant cells in respect to normal ones (In the first 6h after cells interaction with surface) are the key mechanism in our diagnosis procedure. The developed device applied to monitor the spreading-induced electrical differences between cancerous and normal lung cells in an integral fashion. Detection was performed so faster than the time required to complete cells mitosis. Morphology and architecture of doped Si nanowires covered microelectrodes observably enhance the contact area between cells and electrodes which support accurate signal recording from stretched cells as indicated by SEM and florescent images.

Topics: Biosensing Techniques; Electric Impedance; Humans; Lung Neoplasms; Nanowires; Silicon

MicroRNAs (miRNAs) have been regarded as promising biomarkers for the diagnosis and prognosis of early-stage cancer as their expression levels are associated with different types of human cancers. However, it is a challenge to produce low-cost miRNA sensors, as well as retain a high sensitivity, both of which are essential factors that must be considered in fabricating nanoscale biosensors and in future biomedical applications. To address such challenges, we develop a complementary metal oxide semiconductor (CMOS)-compatible SiNW-FET biosensor fabricated by an anisotropic wet etching technology with self-limitation which provides a much lower manufacturing cost and an ultrahigh sensitivity. This nanosensor shows a rapid (< 1 minute) detection of miR-21 and miR-205, with a low limit of detection (LOD) of 1 zeptomole (ca. 600 copies), as well as an excellent discrimination for single-nucleotide mismatched sequences of tumor-associated miRNAs. To investigate its applicability in real settings, we have detected miRNAs in total RNA extracted from lung cancer cells as well as human serum samples using the nanosensors, which demonstrates their potential use in identifying clinical samples for early diagnosis of cancer.

Topics: Base Pair Mismatch; Base Sequence; Biomarkers, Tumor; Biosensing Techniques; Electric Conductivity; Equipment Design; Equipment Failure Analysis; Humans; Lung Neoplasms; MicroRNAs; Molecular Sequence Data; Nanowires; Reproducibility of Results; Sensitivity and Specificity; Sequence Analysis, RNA; Silicon; Staining and Labeling; Transistors, Electronic; Tumor Cells, Cultured

Understanding the effect of alpha radiation on biological systems is an important component of radiation risk assessment and associated health consequences. However, due to the short path length of alpha radiation in the atmosphere, in vitro radiobiological experiments cannot be performed with accuracy in terms of dose and specified exposure time. The present paper describes the design and dosimetry of an automated alpha-particle irradiator named 'BARC BioAlpha', which is suitable for in vitro radiobiological studies. Compared to alpha irradiators developed in other laboratories, BARC BioAlpha has integrated computer-controlled movement of the alpha-particle source, collimator, and electronic shutter. The diaphragm blades of the electronic shutter can control the area (diameter) of irradiation without any additional shielding, which is suitable for radiobiological bystander studies. To avoid irradiation with incorrect parameters, a software interlock is provided to prevent shutter opening, unless the user-specified speed of the source and collimator are achieved. The dosimetry of the alpha irradiator using CR-39 and silicon surface barrier detectors showed that ~4 MeV energy of the alpha particle reached the cells on the irradiation dish. The alpha irradiation was also demonstrated by the evaluation of DNA double-strand breaks in human cells. In conclusion, 'BARC BioAlpha' provides a user-friendly alpha irradiation system for radiobiological experiments with a novel automation mechanism for better accuracy of dose and exposure time.

Topics: Alpha Particles; Cell Line, Tumor; DNA; Dose-Response Relationship, Radiation; Humans; In Vitro Techniques; Lung Neoplasms; Polyethylene Glycols; Radiobiology; Radiometry; Silicon; Software; Time Factors

We experimentally demonstrate label-free photonic crystal (PC) microcavity biosensors in silicon-on-insulator (SOI) to detect the epithelial-mesenchymal transition (EMT) transcription factor, ZEB1, in minute volumes of sample. Multiplexed specific detection of ZEB1 in lysates from NCI-H358 lung cancer cells down to an estimated concentration of 2 cells per micro-liter is demonstrated. L13 photonic crystal microcavities, coupled to W1 photonic crystal waveguides, are employed in which resonances show high Q in the bio-ambient phosphate buffered saline (PBS). When the sensor surface is derivatized with a specific antibody, the binding of the corresponding antigen from a complex whole-cell lysate generates a change in refractive index in the vicinity of the photonic crystal microcavity, leading to a change in the resonance wavelength of the resonance modes of the photonic crystal microcavity. The shift in the resonance wavelength reveals the presence of the antigen. The sensor cavity has a surface area of ∼11μm(2). Multiplexed sensors permit simultaneous detection of many binding interactions with specific immobilized antibodies from the same bio-sample at the same instant of time. Specificity was demonstrated using a sandwich assay which further amplifies the detection sensitivity at low concentrations. The device represents a proof-of-concept demonstration of label-free, high throughput, multiplexed detection of cancer cells with specificity and sensitivity on a silicon chip platform.

Topics: Biomarkers, Tumor; Biosensing Techniques; Cell Line, Tumor; Crystallization; Equipment Design; Equipment Failure Analysis; Homeodomain Proteins; Humans; Immunoassay; Lung Neoplasms; Miniaturization; Refractometry; Silicon; Staining and Labeling; Transcription Factors; Zinc Finger E-box-Binding Homeobox 1

An increased lung cancer risk associated with total dust exposure in the silicon carbide (SiC) industry has previously been reported. The aim of the present study was to examine the relative importance of specific exposure factors by using a comprehensive, historic job exposure matrix based on about 8000 measurements.. Cumulative exposure to total and respirable dust, respirable quartz, cristobalite, and SiC particles and SiC fibres was assessed for 1687 long-term workers employed during 1913-2003 in the Norwegian SiC industry. Standardised incidence ratios for lung cancer, with follow-up during 1953-2008, were calculated stratified by cumulative exposure categories. Poisson regression analyses were performed using both categorised and log-transformed cumulative exposure variables.. The lung cancer incidence was about twofold increased at the highest level of exposure to each of the exposure factors (standardised incidence ratios 1.9-2.3 for all agents). Internal analyses showed associations between exposure level and lung cancer incidence for all investigated factors, but a significant trend only for total dust and cristobalite. In multivariate analyses, cristobalite showed the most consistent associations, followed by SiC fibres.. The results indicated that crystalline silica in the form of cristobalite was the most important occupational exposure factor responsible for lung cancer excess in the Norwegian SiC industry. SiC fibres seemed to have an additional effect.

Topics: Carbon Compounds, Inorganic; Chemical Industry; Dust; Follow-Up Studies; Humans; Incidence; Lung Neoplasms; Male; Multivariate Analysis; Norway; Occupational Diseases; Occupational Exposure; Occupations; Particulate Matter; Poisson Distribution; Silicon; Silicon Compounds; Silicon Dioxide

A mold-cast polydimethylsiloxane (PDMS) confined window was integrated with a poly-silicon wire (PSW) ion sensor. The PSW sensor surface inside the confined window was coated with a 3-aminopropyltriethoxysilane (γ-APTES) sensitive layer which allowed a single living cell to be cultivated. The change in the microenvironment due to the extracellular acidification of the single cell could then be determined by measuring the current flowing through the PSW channel. Based on this, the PSW sensor integrated with a confined sensitive window was used to detect the apoptosis as well as the effect of anti-cancer medicines on the single living non-small-lung-cancer (NSLC) cells including lung adenocarcinoma cancer cells A549 and H1299, and lung squamous-cell carcinoma CH27 cultivated inside the confined window. Single human normal cells including lung fibroblast cells WI38, lung fibroblast cells MRC5, and bronchial epithelium cell Beas-2B were tested for comparison. Two targeted anti-NSCLC cancer medicines, Iressa and Staurosporine, were used in the present study. It was found that the PSW sensor can be used to accurately detect the apoptosis of single cancer cells after the anti-cancer medicines were added. It was also found that Staurosporine is more effective than Iressa in activating the apoptosis of cancer cells.

Topics: Adenocarcinoma; Adenocarcinoma of Lung; Antineoplastic Agents; Apoptosis; Biosensing Techniques; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Drug Delivery Systems; Gefitinib; Humans; Ions; Lung Neoplasms; Propylamines; Quinazolines; Silanes; Silicon; Single-Cell Analysis; Staurosporine

A 59-year-old woman was referred for a diagnostic video thoracoscopy under general anesthesia. At the end of the procedure, the patient presented with subcutaneous emphysema and cyanosis, abdominal distension, and bradycardia. A rigid bronchoscopy showed a longitudinal laceration in the pars membranacea of the trachea. A tracheal silicon stent was positioned on an emergency basis. She was intubated, positioning the tracheal tube cuff distal of the stent under bronchoscopic vision. A computed tomographic scan performed immediately after the procedure showed left pneumothorax, pneumoperitoneum, pneumopericardium, and diffuse subcutaneous emphysema. The subsequent course of the patient was uneventful. The patient was discharged home on postoperative day 4. After 1 year, the stent was removed with the evidence of complete trachel healing.

Topics: Breast Neoplasms; Bronchoscopy; Cyanosis; Female; Follow-Up Studies; Humans; Iatrogenic Disease; Intubation, Intratracheal; Lacerations; Lung Neoplasms; Middle Aged; Pneumoperitoneum; Pneumothorax; Risk Assessment; Silicon; Stents; Subcutaneous Emphysema; Thoracoscopy; Tomography, X-Ray Computed; Trachea; Treatment Outcome

The deformable lung phantom was developed to account for the patient breathing motion, and to evaluate for a deformable image registration algorithm. The phantom consisted of an acryl cylinder filled with water and a latex balloon located in the inner space of the cylinder. A silicon membrane was attached to the inferior end of the phantom. This silicon membrane was designed to simulate a real lung diaphragm and to reduce motor workload. This specific design was able to reduce the metal use which may prevent infrared sensing of the real position management (RPM) gating system on 4D CT image acquisition. Verification of intensity based 3D demon deformable registration was based on peak exhale and peak inhale breathing phases. The registration differences ranged from 0.85 mm to 1.47 mm, and accuracy was determined according to inner target deformation. This phantom was able to simulate the features and deformation of real human lung and has the potential for wide application in 4D radiation treatment planning.

Topics: Acrylates; Algorithms; Artifacts; Four-Dimensional Computed Tomography; Humans; Latex; Lung; Lung Neoplasms; Phantoms, Imaging; Radiographic Image Interpretation, Computer-Assisted; Reproducibility of Results; Respiratory Mechanics; Sensitivity and Specificity; Silicon; Water

Topics: Aged; Breast Neoplasms; Female; Humans; Lung Neoplasms; Lymphadenitis; Mediastinal Diseases; Neoplasm Recurrence, Local; Neoplasms, Multiple Primary; Silicon

We performed infrared (IR) spectroscopic imaging of molecular species in cultured cell interiors of A549 cells using in-house developed vibrational sum-frequency generation detected IR super-resolution microscope. The spatial resolution of this IR microscope was approximately 1.1 microm, which exceeds the diffraction limit of IR light. Therefore, we clearly observed differences in the signal intensity at various IR wavelengths which appear to originate from the differing IR absorptions of specific vibrational modes, and reveal the distribution of molecular species in the single cell. These results were never imaged with the conventional IR microscope.

Topics: Cell Biology; Cell Line, Tumor; Electron Transport; Equipment Design; Humans; Infrared Rays; Lung Neoplasms; Microscopy; Silicon; Spectrum Analysis, Raman; Vibration

We investigate the potential of megavoltage (MV) cone-beam CT with an amorphous silicon electronic portal imaging device (EPID) as a tool for patient position verification and tumor/organ motion studies in radiation treatment of lung tumors. We acquire 25 to 200 projection images using a 22 x 29 cm EPID. The acquisition is automatic and requires 7 minutes for 100 projections; it can be synchronized with respiratory gating. From these images, volumetric reconstruction is accomplished with a filtered backprojection in the cone-beam geometry. Several important prereconstruction image corrections, such as detector sag, must be applied. Tests with a contrast phantom indicate that differences in electron density of 2% can be detected with 100 projections, 200 cGy total dose. The contrast-to-noise ratio improves as the number of projections is increased. With 50 projections (100 cGy), high contrast objects are visible, and as few as 25 projections yield images with discernible features. We identify a technique of acquiring projection images with conformal beam apertures, shaped by a multileaf collimator, to reduce the dose to surrounding normal tissue. Tests of this technique on an anthropomorphic phantom demonstrate that a gross tumor volume in the lung can be accurately localized in three dimensions with scans using 88 monitor units. As such, conformal megavoltage cone-beam CT can provide three-dimensional imaging of lung tumors and may be used, for example, in verifying respiratory gated treatments.

Topics: Algorithms; Biophysical Phenomena; Biophysics; Calibration; Humans; Image Processing, Computer-Assisted; Lung Neoplasms; Particle Accelerators; Phantoms, Imaging; Radiography, Thoracic; Radiotherapy; Radiotherapy, Conformal; Silicon; Tomography, X-Ray Computed

The role of silicosis as either a necessary or incidental condition in silica associated lung cancer remains unresolved. To address this issue a cohort analysis of dose-response relations for crystalline silica and lung cancer mortality was conducted among diatomaceous earth workers classified according to the presence or absence of radiological silicosis.. Radiological silicosis was determined by median 1980 International Labour Organisation system readings of a panel of three "B" readers for 1809 of 2342 white male workers in a diatomaceous earth facility in California. Standardised mortality ratios (SMR) for lung cancer, based on United States rates for 1942-94, were calculated separately for workers with and without radiological silicosis according to cumulative exposures to respirable crystalline silica (milligrams per cubic meter x years; mg/m3-years) lagged 15 years.. Eighty one cases of silicosis were identified, including 77 with small opacities of > or = 1/0 and four with large opacities. A slightly larger excess of lung cancer was found among the subjects with silicosis (SMR 1.57, 95% confidence interval (CI) 0.43 to 4.03) than in workers without silicosis (SMR 1.19, 95% CI 0.87 to 1.57). An association between silica exposure and lung cancer risk was detected among those without silicosis; a statistically significant (p = 0.02) increasing trend of lung cancer risk was seen with cumulative exposure, with SMR reaching 2.40 (95% CI 1.24 to 4.20) at the highest exposure level (> or = 5.0 mg/m3-years). A similar statistically significant (p = 0.02) dose-response gradient was observed among non-silicotic subjects when follow up was truncated at 15 years after the final negative radiograph (SMR 2.96, 95% CI 1.19 to 6.08 at > or = 5.0 mg/m3-years), indicating that the association among non-silicotic subjects was unlikely to be accounted for by undetected radiological silicosis.. The dose-response relation observed between cumulative exposure to respirable crystalline silica and lung cancer mortality among workers without radiological silicosis suggests that silicosis is not a necessary co-condition for silica related lung carcinogenesis. However, the relatively small number of silicosis cases in the cohort and the absence of radiographic data after employment limit interpretations.

Topics: Adult; Aged; California; Cohort Studies; Dust; Humans; Lung Neoplasms; Male; Middle Aged; Occupational Exposure; Silicon; Silicosis

A 60-year-old man, employed as a welder for 25 years, was admitted with an abnormal shadow on chest X-ray. An ill-defined and solitary mass shadow 3 cm in diameter was subsequently detected in the left upper lung field. The mass shadow exhibited high attenuation on chest CT scan. Transbronchial lung biopsy (TBLB) revealed an organized lesion possessing a large quantity of iron. Although pneumoconiosis was suspected, the possibility of lung cancer could not be dismissed. Pneumoconiosis (welder's lung) was diagnosed after thoracotomy and examination of the resected mass. Pneumoconiosis (welder's lung) rarely presents as a solitary mass lesion.

Topics: Diagnosis, Differential; Humans; Iron; Lung Neoplasms; Male; Middle Aged; Pneumoconiosis; Radiography; Silicon

To determine whether inhaled silicon carbide whiskers (SiC) cause lung damage in rats, four groups (50 males/50 females each) of rats were exposed to air only or to one of three concentrations of SiC 6 hr/day, 5 days/week for 13 weeks. Half (25 males/25 females/group) were euthanized at the end of exposure, the remainder 26 weeks later. Mean concentrations were 0, 630, 1746, and 7276 SiC whiskers/ml (0.09, 3.93, 10.7, and 60.5 mg/m3). Although there were no concentration-related changes in body weight, clinical chemistry, or hematological data attributable to SiC, lung weights were increased in the high concentration exposure group at both euthanization times. In all whisker-exposed groups, after 13 weeks of exposure, the incidence of the following lung and lymph node lesions was higher than in controls: inflammatory lesions; bronchiolar, alveolar, and pleural wall thickening; focal pleural fibrosis in lung; and reactive lymphoid hyperplasia in bronchial and mediastinal lymph nodes. After 26 weeks of recovery, lung inflammatory lesions had decreased and fewer rats had enlarged lymph nodes, but the incidence of alveolar wall thickening, focal pleural wall thickening, and adenomatous hyperplasia of lung had increased further. Incidence and severity appeared to be dose-related. Therefore, until longer term studies are undertaken and it is established whether the above observed lesions will progress to more severe pathological entities, it is prudent to adopt stringent handling procedures for silicon carbide whiskers.

Topics: Adenoma; Animals; Carbon; Carbon Compounds, Inorganic; Female; Lung; Lung Neoplasms; Lymph Nodes; Male; Microscopy, Electron, Scanning; Organ Size; Pleura; Rats; Rats, Inbred Strains; Silicon; Silicon Compounds

Epidemiologic studies have reported associations between gastrointestinal cancer mortality and exposure to cutting fluids and abrasives in metal machining and precision grinding operations. Two previous studies found excess stomach cancer among workers exposed to water-based cutting fluids in bearing plants. This study reports similar findings in a third and larger population. Cause of death and work histories were determined for 1,766 bearing plant workers who died between Jan 1, 1950 and June 30, 1982. Mortality odds ratios (SMOR) and proportional mortality ratios (PMR) revealed significant excesses of gastrointestinal malignancies. The proportional mortality excess for stomach cancer among white men was greatest among those with more than 10 years' exposure in the major grinding group (PMR = 13/3.8 = 3.39; P less than .001). The SMOR by logistic regression for stomach cancer among white men was 2.3 (P = .02) for 25 years' grinding experience. For cancer of the pancreas among white men, there were significant associations with both machining and grinding jobs in straight oil (SMOR = 9.9 and 3.2, respectively, for 25 years duration). These findings could not be explained by confounding due to the ethnic background of the decedents. This study confirms previous evidence that grinding operations using water-based cutting fluids increase the risk for stomach cancer and provides moderate evidence that exposures to straight oil-cutting fluids increase the risk for cancer of the pancreas. There were indications, meriting further investigation, that non-malignant liver disease is associated with cutting fluid exposures and that lung cancer is associated with oil smoke from operations such as forging or heat treating.

Topics: Aluminum; Aluminum Oxide; Carbon; Carbon Compounds, Inorganic; Chemical and Drug Induced Liver Injury; Connecticut; Female; Humans; Industrial Oils; Liver Diseases; Lung Neoplasms; Male; Metallurgy; Occupational Diseases; Pancreatic Neoplasms; Silicon; Silicon Compounds; Smoke; Stomach Neoplasms

Topics: Aged; Aged, 80 and over; Carcinoma, Bronchogenic; Diagnosis, Differential; Humans; Lung; Lung Neoplasms; Male; Silicon; Silicosis

To evaluate the possible health effects of occupational exposure to a nonasbestos mineral fiber, a cohort of 2,302 males employed for at least 1 month between 1940 and 1975 at an attapulgite (clay fiber) mining and milling facility was followed through 1975. A significant deficit of mortality (SMR = 43, 90% CI 23-76) from nonmalignant respiratory disease (NMRD) was observed for the cohort based on age-, calendar year-, and race-specific rates for U.S. males. A marked deficit of NMRD was seen regardless of presumed dust exposure level, induction-latency period, or duration employed. A statistically significant excess of mortality from lung cancer was observed among whites (SMR = 193, 90% CI 121-293), but a deficit occurred among nonwhites (SMR = 53, 90% CI 21-112). Lung cancer risk in either race was not altered substantially with presumed dust exposure level, induction-latency period, or duration employed with one exception-those employed for at least 5 years in high-exposure-level jobs.

Topics: Dust; Gastrointestinal Neoplasms; Humans; Liver Neoplasms; Lung Neoplasms; Magnesium; Magnesium Compounds; Male; Mining; Occupational Diseases; Retrospective Studies; Risk Factors; Silicon; Silicon Compounds

Topics: Aged; Chromium; Chromium Alloys; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasms; Norway; Occupational Diseases; Prostatic Neoplasms; Silicon; Silicon Compounds

Six reagents used to silylate, alkylate, or acylate compounds for ease of identification on gas chromatographic columns significantly increased the frequency of lung tumors in A/He mice.

Topics: Acetamides; Adenoma; Alkylating Agents; Animals; Chromatography, Gas; Female; Imidazoles; Indicators and Reagents; Lung Neoplasms; Male; Mice; Mice, Inbred A; Neoplasms, Experimental; Silicon; Triazenes

Topics: Animals; Benzopyrenes; Lung Neoplasms; Rats; Silicon; Silicosis