Abstract: Lung cancer is one of the most common malignancies and primary cause of death due to cancer worldwide. Non-small cell lung cancer (NSCLC) is the main subtype in which majority of patients present with advanced-stage disease. Herein, we analyzed differentially expressed genes to find potential biomarkers for lung cancer diagnosis as well as prognostic markers. We used transcriptome data from our 2 NSCLC patients and public data (GSE81089) composing of 8 NSCLC and 10 normal lung tissues. Differentially expressed genes (DEGs) between NSCLC and normal tissue and between early-stage and late-stage NSCLC were analyzed by the DESeq2. Pairwise correlation was used to find the DEGs with false discovery rate (FDR) adjusted p-value £ 0.05 and |log2 fold change| ³ 4 for NSCLC versus normal and FDR adjusted p-value £ 0.05 with |log2 fold change| ³ 2 for early versus late-stage NSCLC. Bioinformatic tools were used for functional and pathway analysis. Moreover, the top ten genes in each comparison group were verified the expression and survival analysis via GEPIA. We found 150 up-regulated and 45 down-regulated genes in NSCLC compared to normal tissues. Many immnunoglobulin-related genes e.g., IGHV4-4, IGHV5-10-1, IGHV4-31, IGHV4-61, and IGHV1-69D were significantly up-regulated. 22 genes were up-regulated, and five genes were down-regulated in late-stage compared to early-stage NSCLC. The top five DEGs genes were KRT6B, SPRR1A, KRT13, KRT6A and KRT5. Keratin 6B (KRT6B) was the most significantly increased gene in the late-stage NSCLC. From GEPIA analysis, we concluded that IGHV4-31 and IGKV1-9 might be used as diagnostic biomarkers, while KRT6B and KRT6A might be used as prognostic biomarkers. However, further clinical validation is needed.
Abstract: Uncontrolled growth of abnormal cells in the lung in the form of tumor can be either benign (non-cancerous) or malignant (cancerous). Patients with Lung Cancer (LC) have an average of five years life span expectancy provided diagnosis, detection and prediction, which reduces many treatment options to risk of invasive surgery increasing survival rate. Computed Tomography (CT), Positron Emission Tomography (PET), and Magnetic Resonance Imaging (MRI) for earlier detection of cancer are common. Gaussian filter along with median filter used for smoothing and noise removal, Histogram Equalization (HE) for image enhancement gives the best results without inviting further opinions. Lung cavities are extracted and the background portion other than two lung cavities is completely removed with right and left lungs segmented separately. Region properties measurements area, perimeter, diameter, centroid and eccentricity measured for the tumor segmented image, while texture is characterized by Gray-Level Co-occurrence Matrix (GLCM) functions, feature extraction provides Region of Interest (ROI) given as input to classifier. Two levels of classifications, K-Nearest Neighbor (KNN) is used for determining patient condition as normal or abnormal, while Artificial Neural Networks (ANN) is used for identifying the cancer stage is employed. Discrete Wavelet Transform (DWT) algorithm is used for the main feature extraction leading to best efficiency. The developed technology finds encouraging results for real time information and on line detection for future research.
Abstract: Background: The incidence of adverse reactions to iodinated contrast media has risen. The dearth of reports on reactions to the administration of iso- and low-osmolar contrast media should be addressed. We, therefore, studied the profile of adverse reactions to iodinated contrast media; viz., (a) the body systems affected (b) causality, (c) severity, and (d) preventability. Objective: To study adverse reactions (causes and severity) to iodinated contrast media at Srinagarind Hospital. Method: Between March and July, 2015, 1,101 patients from the Department of Radiology were observed and interviewed for the occurrence of adverse reactions. The patients were classified per Naranjo’s algorithm and through use of an adverse reactions questionnaire. Results: A total of 105 cases (9.5%) reported adverse reactions (57% male; 43% female); among whom 2% were iso-osmolar vs. 98% low-osmolar. Diagnoses included hepatoma and cholangiocarcinoma (24.8%), colorectal cancer (9.5%), breast cancer (5.7%), cervical cancer (3.8%), lung cancer (2.9%), bone cancer (1.9%), and others (51.5%). Underlying diseases included hypertension and diabetes mellitus type 2. Mild, moderate, and severe adverse reactions accounted for 92, 5 and 3%, respectively. The respective groups of escalating symptoms included (a) mild urticaria, itching, rash, nausea, vomiting, dizziness, and headache; (b) moderate hypertension, hypotension, dyspnea, tachycardia and bronchospasm; and (c) severe laryngeal edema, profound hypotension, and convulsions. All reactions could be anticipated per Naranjo’s algorithm. Conclusion: Mild to moderate adverse reactions to low-osmolar contrast media were most common and these occurred immediately after administration. For patient safety and better outcomes, improving the identification of patients likely to have an adverse reaction is essential.
Abstract: Usually, phosphate deposits contain 238U and 232Th in addition to their decay products. Due to their different pathways in the environment, the 238U/232Th activity concentration ratio usually found to be greater than unity in phosphate sediments. The presence of these radionuclides creates a potential need to control exposure of workers in the mining and processing activities of the phosphate minerals in accordance with IAEA safety standards. The greatest dose to workers comes from exposure to radon, especially 222Rn from the uranium series, and has to be controlled. In this regard, radon (222Rn) was measured in the atmosphere (indoor and outdoor) of Al-Jalamid phosphate-mines working area using a portable radon-measurement instrument RAD7, in a purpose of radiation protection. Radon was measured in 61 sites inside the open phosphate mines, the phosphate upgrading facility (offices and rooms of the workers, and in some open-air sites) and in the dwellings of the workers residence-village that lies at about 3 km from the mines working area. The obtained results indicated that the average indoor radon concentration was about 48.4 Bq/m3. Inside the upgrading facility, the average outdoor concentrations were 10.8 and 9.7 Bq/m3 in the concentrate piles and crushing areas, respectively. It was 12.3 Bq/m3 in the atmosphere of the open mines. These values are comparable with the global average values. Based on the average values, the annual effective dose due to radon inhalation was calculated and risk estimates have been done. The average annual effective dose to workers due to the radon inhalation was estimated by 1.32 mSv. The potential excess risk of lung cancer mortality that could be attributed to radon, when considering the lifetime exposure, was estimated by 53.0x10-4. The results have been discussed in detail.
Abstract: Metabolomics has become a rising field of research
for various diseases, particularly cancer. Increases or decreases in
metabolite concentrations in the human body are indicative of various
cancers. Further elucidation of metabolic pathways and their
significance in cancer research may greatly spur medicinal discovery.
We analyzed the metabolomics profiles of lung cancer. Thirty-three
metabolites were selected as significant. These metabolites are
involved in 37 metabolic pathways delivered by MetaboAnalyst
software. The top pathways are glyoxylate and dicarboxylate
pathway (its hubs are formic acid and glyoxylic acid) along with
Citrate cycle pathway followed by Taurine and hypotaurine pathway
(the hubs in the latter are taurine and sulfoacetaldehyde) and Glycine,
serine, and threonine pathway (the hubs are glycine and L-serine). We
studied interactions of the metabolites with the proteins involved in
cancer-related signaling networks, and developed an approach to
metabolomics biomarker use in cancer diagnostics. Our analysis
showed that a significant part of lung-cancer-related metabolites
interacts with main cancer-related signaling pathways present in this
network: PI3K–mTOR–AKT pathway, RAS–RAF–ERK1/2 pathway,
and NFKB pathway. These results can be employed for use of
metabolomics profiles in elucidation of the related cancer proteins
signaling networks.
Abstract: Design criteria for achieving an acceptable indoor radon concentration are presented in this paper. The paper suggests three design criteria. These criteria have to be considered at the early stage of the building design phase to meet the latest recommendations from the World Health Organization in most countries. The three design criteria are; first, establishing a radon barrier facing the ground; second, lowering the air pressure in the lower zone of the slab on ground facing downwards; third, diluting the indoor air with outdoor air. The first two criteria can prevent radon from infiltrating from the ground, and the third criteria can dilute the indoor air. By combining these three criteria, the indoor radon concentration can be lowered achieving an acceptable level. In addition, a cheap and reliable method for measuring the radon concentration in the indoor air is described. The provision on radon in the Danish Building Regulations complies with the latest recommendations from the World Health Organization. Radon can cause lung cancer and it is not known whether there is a lower limit for when it is not harmful to human beings. Therefore, it is important to reduce the radon concentration as much as possible in buildings. Airtightness is an important factor when dealing with buildings. It is important to avoid air leakages in the building envelope both facing the atmosphere, e.g. in compliance with energy requirements, but also facing the ground, to meet the requirements to ensure and control the indoor environment. Infiltration of air from the ground underneath a building is the main providing source of radon to the indoor air.
Abstract: MicroRNAs are small non-coding RNA found in
many different species. They play crucial roles in cancer such as
biological processes of apoptosis and proliferation. The identification
of microRNA-target genes can be an essential first step towards to
reveal the role of microRNA in various cancer types. In this paper,
we predict miRNA-target genes for lung cancer by integrating
prediction scores from miRanda and PITA algorithms used as a
feature vector of miRNA-target interaction. Then, machine-learning
algorithms were implemented for making a final prediction. The
approach developed in this study should be of value for future studies
into understanding the role of miRNAs in molecular mechanisms
enabling lung cancer formation.
Abstract: Noninvasive diagnostics of diseases via breath
analysis has attracted considerable scientific and clinical interest for
many years and become more and more promising with the rapid
advancements in nanotechnology and biotechnology. The volatile
organic compounds (VOCs) in exhaled breath, which are mainly
blood borne, particularly provide highly valuable information about
individuals’ physiological and pathophysiological conditions.
Additionally, breath analysis is noninvasive, real-time, painless, and
agreeable to patients. We have developed a wireless sensor array
based on single-stranded DNA (ssDNA)-functionalized single-walled
carbon nanotubes (SWNT) for the detection of a number of
physiological indicators in breath. Seven DNA sequences were used
to functionalize SWNT sensors to detect trace amount of methanol,
benzene, dimethyl sulfide, hydrogen sulfide, acetone, and ethanol,
which are indicators of heavy smoking, excessive drinking, and
diseases such as lung cancer, breast cancer, and diabetes. Our test
results indicated that DNA functionalized SWNT sensors exhibit
great selectivity, sensitivity, and repeatability; and different
molecules can be distinguished through pattern recognition enabled
by this sensor array. Furthermore, the experimental sensing results
are consistent with the Molecular Dynamics simulated ssDNAmolecular
target interaction rankings. Thus, the DNA-SWNT sensor
array has great potential to be applied in chemical or biomolecular
detection for the noninvasive diagnostics of diseases and personal
health monitoring.
Abstract: Doxorubicin, also known as Adriamycin, is an
anthracycline class of drug used in cancer chemotherapy. It is used in
the treatment of non-Hodgkin’s lymphoma, multiple myeloma, acute
leukemia, breast cancer, lung cancer, endometrium cancer and ovary
cancers. It functions via intercalating DNA and ultimately killing
cancer cells. The major side effects of doxorubicin are hair loss,
myelosuppression, nausea & vomiting, oesophagitis, diarrhea, heart
damage and liver dysfunction. The minor modifications in the
structure of compound exhibit large variation in the biological
activity, has prompted us to carry out the synthesis of sulfonamide
derivatives. Sulfonamide is an important feature with broad spectrum
of biological activity such as antiviral, antifungal, diuretics, antiinflammatory,
antibacterial and anticancer activities. Structure of the
synthesized compound N-(1-methyl-2-oxo-2-N-methyl anilinoethyl)
benzene sulfonamide confirmed by proton nuclear magnetic
resonance (1H NMR),13C NMR, Mass and FTIR spectroscopic tools
to assure the position of all protons and hence stereochemistry of the
molecule. Further we have reported the binding potential of
synthesized sulfonamide analogues in comparison to doxorubicin
drug using Auto Dock 4.2 software. Computational binding energy
(B.E.) and inhibitory constant (Ki) has been evaluated for the
synthesized compound in comparison of doxorubicin against Poly
(dA-dT).Poly (dA-dT) and Poly (dG-dC).Poly (dG-dC) sequences.
The in vitro cytotoxic study against human breast cancer cell lines
confirms the better anticancer activity of the synthesized compound
over currently in use anticancer drug doxorubicin. The IC50 value of
the synthesized compound is 7.12 μM whereas for doxorubicin is 7.2
μM.
Abstract: Purpose: To explore the use of Curvelet transform to
extract texture features of pulmonary nodules in CT image and support
vector machine to establish prediction model of small solitary
pulmonary nodules in order to promote the ratio of detection and
diagnosis of early-stage lung cancer. Methods: 2461 benign or
malignant small solitary pulmonary nodules in CT image from 129
patients were collected. Fourteen Curvelet transform textural features
were as parameters to establish support vector machine prediction
model. Results: Compared with other methods, using 252 texture
features as parameters to establish prediction model is more proper.
And the classification consistency, sensitivity and specificity for the
model are 81.5%, 93.8% and 38.0% respectively. Conclusion: Based
on texture features extracted from Curvelet transform, support vector
machine prediction model is sensitive to lung cancer, which can
promote the rate of diagnosis for early-stage lung cancer to some
extent.
Abstract: In this paper we describe a computer-aided diagnosis (CAD) system for automated detection of pulmonary nodules in computed-tomography (CT) images. After extracting the pulmonary parenchyma using a combination of image processing techniques, a region growing method is applied to detect nodules based on 3D geometric features. We applied the CAD system to CT scans collected in a screening program for lung cancer detection. Each scan consists of a sequence of about 300 slices stored in DICOM (Digital Imaging and Communications in Medicine) format. All malignant nodules were detected and a low false-positive detection rate was achieved.
Abstract: Early detection of lung cancer through chest radiography is a widely used method due to its relatively affordable cost. In this paper, an approach to improve lung nodule visualization on chest radiographs is presented. The approach makes use of linear phase high-frequency emphasis filter for digital filtering and
histogram equalization for contrast enhancement to achieve improvements. Results obtained indicate that a filtered image can
reveal sharper edges and provide more details. Also, contrast enhancement offers a way to further enhance the global (or local) visualization by equalizing the histogram of the pixel values within
the whole image (or a region of interest). The work aims to improve lung nodule visualization of chest radiographs to aid detection of lung cancer which is currently the leading cause of cancer deaths worldwide.
Abstract: Before performing polymerase chain reactions (PCR), a feasible primer set is required. Many primer design methods have been proposed for design a feasible primer set. However, the majority of these methods require a relatively long time to obtain an optimal solution since large quantities of template DNA need to be analyzed. Furthermore, the designed primer sets usually do not provide a specific PCR product. In recent years, evolutionary computation has been applied to PCR primer design and yielded promising results. In this paper, a particle swarm optimization (PSO) algorithm is proposed to solve primer design problems associated with providing a specific product for PCR experiments. A test set of the gene CYP1A1, associated with a heightened lung cancer risk was analyzed and the comparison of accuracy and running time with the genetic algorithm (GA) and memetic algorithm (MA) was performed. A comparison of results indicated that the proposed PSO method for primer design finds optimal or near-optimal primer sets and effective PCR products in a relatively short time.
Abstract: Segmentation is an important step in medical image
analysis and classification for radiological evaluation or computer
aided diagnosis. The CAD (Computer Aided Diagnosis ) of lung CT
generally first segment the area of interest (lung) and then analyze
the separately obtained area for nodule detection in order to
diagnosis the disease. For normal lung, segmentation can be
performed by making use of excellent contrast between air and
surrounding tissues. However this approach fails when lung is
affected by high density pathology. Dense pathologies are present in
approximately a fifth of clinical scans, and for computer analysis
such as detection and quantification of abnormal areas it is vital that
the entire and perfectly lung part of the image is provided and no
part, as present in the original image be eradicated. In this paper we
have proposed a lung segmentation technique which accurately
segment the lung parenchyma from lung CT Scan images. The
algorithm was tested against the 25 datasets of different patients
received from Ackron Univeristy, USA and AGA Khan Medical
University, Karachi, Pakistan.
Abstract: Lung cancer accounts for the most cancer related deaths for men as well as for women. The identification of cancer associated genes and the related pathways are essential to provide an important possibility in the prevention of many types of cancer. In this work two filter approaches, namely the information gain and the biomarker identifier (BMI) are used for the identification of different types of small-cell and non-small-cell lung cancer. A new method to determine the BMI thresholds is proposed to prioritize genes (i.e., primary, secondary and tertiary) using a k-means clustering approach. Sets of key genes were identified that can be found in several pathways. It turned out that the modified BMI is well suited for microarray data and therefore BMI is proposed as a powerful tool for the search for new and so far undiscovered genes related to cancer.
Abstract: Cancer becomes one of the leading cause of death in
many countries over the world. Fourier-transform infrared (FTIR)
spectra of human lung cancer cells (A549) treated with PMF (natural
product extracted from PM 701) for different time intervals were
examined. Second derivative and difference method were taken in
comparison studies. Cesium (Cs) and Rubidium (Rb) nanoparticles in
PMF were detected by Energy Dispersive X-ray attached to Scanning
Electron Microscope SEM-EDX. Characteristic changes in protein
secondary structure, lipid profile and changes in the intensities of
DNA bands were identified in treated A549 cells spectra. A
characteristic internucleosomal ladder of DNA fragmentation was
also observed after 30 min of treatment. Moreover, the pH values
were significantly increases upon treatment due to the presence of Cs
and Rb nanoparticles in the PMF fraction. These results support the
previous findings that PMF is selective anticancer agent and can
produce apoptosis to A549 cells.
Abstract: This article outlines conceptualization and
implementation of an intelligent system capable of extracting
knowledge from databases. Use of hybridized features of both the
Rough and Fuzzy Set theory render the developed system flexibility
in dealing with discreet as well as continuous datasets. A raw data set
provided to the system, is initially transformed in a computer legible
format followed by pruning of the data set. The refined data set is
then processed through various Rough Set operators which enable
discovery of parameter relationships and interdependencies. The
discovered knowledge is automatically transformed into a rule base
expressed in Fuzzy terms. Two exemplary cancer repository datasets
(for Breast and Lung Cancer) have been used to test and implement
the proposed framework.