Search results for: lung tumor

Authors: Paul J Yazaki, Michael Bouvet, John Shively

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Surgery for solid gastrointestinal (GI) cancers such as pancreatic, colorectal, and gastric adenocarcinoma remains the mainstay of curative therapy. Complete resection of the primary tumor with negative margins (R0 resection), its draining lymph nodes, and distant metastases offers the optimal surgical benefit. Real-time fluorescence guided surgery (FGS) promises to improve GI cancer outcomes and is rapidly advancing with tumor-specific antibody conjugated fluorophores that can be imaged using near infrared (NIR) technology. Carcinoembryonic Antigen (CEA) is a non-internalizing tumor antigen validated as a surface tumor marker expressed in >95% of colorectal, 80% of gastric, and 60% of pancreatic adenocarcinomas. Our humanized anti-CEA hT84.66-M5A (M5A) monoclonal antibody (mAb)was conjugated with the NHS-IRDye800CW fluorophore and shown it can rapidly and effectively NIRoptical imageorthotopically implanted human colon and pancreatic cancer in mouse models. A limitation observed is that these NIR-800 dye conjugated mAbs have a rapid clearance from the blood, leading to a narrow timeframe for FGS and requiring high doses for effective optical imaging. We developed a novel antibody-fluorophore conjugate by incorporating a PEGylated sidearm linker to shield or mask the IR800 dye’s hydrophobicity which effectively extended the agent’s blood circulation half-life leading to increased tumor sensitivity and lowered normal hepatic uptake. We hypothesized that our unique anti-CEA linked to the fluorophore, IR800 by PEGylated sidewinder, M5A-SW-IR800 will become the next generation optical imaging agent, safe, effective, and widely applicable for intraoperative image guided surgery in CEA expressing GI cancers.

Keywords: optical imaging, anti-CEA, cancer, fluorescence-guided surgery

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Authors: Hossain A, Hossain S.

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Introduction: In a small cohort, we sought to assess the magnetic resonance spectroscopy's (MRS) ability to predict the presence of metastatic lesions. Method: A Popular Diagnostic Centre Limited enrolled patients with neuroepithelial tumors. The 1H CSI MRS of the brain allows us to detect changes in the concentration of specific metabolites caused by metastatic lesions. Among these metabolites are N-acetyl-aspartate (NNA), creatine (Cr), and choline (Cho). For Cho, NAA, Cr, and Cr₂, the metabolic ratio was calculated using the division method. Results: The NAA values were 0.63 and 5.65 for tumor cells, 1.86 and 5.66 for normal cells, and 1.86 and 5.66 for normal cells 2. NAA values for normal cells 1 were 1.84, 10.6, and 1.86 for normal cells 2, respectively. Cho levels were as low as 0.8 and 10.53 in the tumor cell, compared to 1.12 and 2.7 in the normal cell 1 and 1.24 and 6.36 in the normal cell 2. Cho/Cr₂ barely distinguished itself from the other ratios in terms of significance. For tumor cells, the ratios of Cho/NAA, Cho/Cr₂, NAA/Cho, and NAA/Cr₂ were significant. Normal cell 1 had significant Cho/NAA, Cho/Cr, NAA/Cho, and NAA/Cr ratios. Conclusion: The clinical result can be improved by using 1H-MRSI to guide the size of resection for metastatic lesions. Even though it is non-invasive and doesn't present any difficulties during the procedure, MRS has been shown to predict the detection of metastatic lesions.

Keywords: metabolite ratio, MRI images, metastatic lesion, MR spectroscopy, N-acetyl-aspartate

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Authors: Jaiden X. Schraut

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Medical Imaging Segmentation of Chest X-rays is used for the purpose of identification and differentiation of lung cancer, pneumonia, COVID-19, and similar respiratory diseases. Widespread application of computer-supported perception methods into the diagnostic pipeline has been demonstrated to increase prognostic accuracy and aid doctors in efficiently treating patients. Modern models attempt the task of segmentation and classification separately and improve diagnostic efficiency; however, to further enhance this process, this paper proposes a multi-output network that follows a U-Net architecture for image segmentation output and features an additional CNN module for auxiliary classification output. The proposed model achieves a final Jaccard Index of .9634 for image segmentation and a final accuracy of .9600 for classification on the COVID-19 radiography database.

Keywords: chest X-ray, deep learning, image segmentation, image classification

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Authors: H. M. Abdelmoneim, N. A. Babtain, A. S. Barhamain, A. Z. Kufiah, A. S. Malibari, S. F. Munassar, R. S. Rawa

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Introduction: Prostate cancer is one of the most common causes of morbidity and mortality in men in developed countries. Cancer Stem Cells (CSCs) could be responsible for the progression and relapse of cancer. Therefore, CSCs markers could provide a prognostic strategy for human malignancies. Aldehyde dehydrogenase 1A1 (ALDH1A1) activity has been shown to be associated with tumorigenesis and proposed to represent a functional marker for tumor initiating cells in various tumor types including prostate cancer. Material & Methods: We analyzed the immunohistochemical expression of ALDH1A1 in benign prostatic hyperplasia (BPH), prostatic intraepithelial neoplasia (PIN) and prostatic adenocarcinoma and assessed their significant correlations in 50 TURP sections. They were microscopically interpreted and the results were correlated with histopathological types and tumor grade. Results: In different prostatic histopathological lesions we found that ALDH1A1 expression was low in BPH (13.3%) and PIN (6.7%) and then its expression increased with prostatic adenocarcinoma (40%), and this was statistically highly significant (P value = 0.02). However, in different grades of prostatic adenocarcinoma we found that the higher the Gleason grade the higher the expression for ALDH1A1 and this was statistically significant (P value = 0.02). We compared the expression of ALDH1A1 in PIN and prostatic adenocarcinoma. ALDH1A1 expression was decreased in PIN and highly expressed in prostatic adenocarcinoma and this was statistically significant (P value = 0.04). Conclusion: Increasing ALDH1A1 expression is correlated with aggressive behavior of the tumor. Immunohistochemical expression of ALDH1A1 might provide a potential approach to study tumorigenesis and progression of primary prostate carcinoma.

Keywords: ALDH1A1, BPH, PIN, prostatic adenocarcinoma

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Authors: M. Mousavi-Daramoroudi, H. Yousefnia, F. Abbasi-Davani, S. Zolghadri, S. Kakaei

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Despite the appropriate characteristics of ¹⁷⁷Lu and DOTATOC, to our best knowledge, the therapeutic benefit of ¹⁷⁷Lu-DOTATOC complex in breast cancer has not been reported until now. In this study, biodistribution of ¹⁷⁷Lu-DOTA-TOC in mouse tumor model for evaluation of possible utilization of this complex in breast cancer treatment was investigated.¹⁷⁷Lu was prepared with the specific activity of 2.6-3 GBq.mg^-1 and radionuclidic purity higher than 99%. The radiolabeled complex was prepared in the optimized conditions with the radiochemical purity higher than 99%. The final solution was injected to the BALB/c mice with adenocarcinoma breast cancer. The biodistribution results showed major accumulation in the kidneys as the major excretion route and the somatostatin receptor-positive tissues such as pancreas compared with the other tissues. Also, significant uptake was observed in tumor even in longer time after injection. According to the results obtained in this research study, somatostatin receptors expressed in breast cancers can be targeted with DOTATOC analogues especially with ¹⁷⁷Lu-DOTATOC as an ideal therapeutic agent.

Keywords: ¹⁷⁷Lu, adenocarcinoma breast cancer, DOTATOC, BALB/c mice

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Authors: Mohammad Ali Oghabian, Reza Reiazi, Esmaeel Parsai, Mehdi Aghili, Ramin Jaberi

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In this project a new procedure has been introduced for utilizing digitally reconstructed radiograph from MRI images in Brachytherapy treatment planning. This procedure enables us to localize the tumor volume and delineate the extent of critical structures in vicinity of tumor volume. The aim of this project was to improve the accuracy of dose delivered to targets of interest in 2D treatment planning system.

Keywords: brachytherapy, cervix, digitally reconstructed radiographs, lymph node

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Authors: Lubomir Vecera, Tomas Gabrhelik, Benjamin Tolmaci, Josef Srovnal, Emil Berta, Petr Prasil, Petr Stourac

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Cancer is the second leading cause of death worldwide and colon cancer is the second most common type of cancer. Currently, there are only a few studies evaluating the effect of postoperative analgesia on the prognosis of patients undergoing radical colon cancer surgery. Postoperative analgesia in patients undergoing colon cancer surgery is usually managed in two ways, either with strong opioids (morphine, piritramide) or epidural analgesia. In our prospective study, we evaluated the effect of postoperative analgesia on the presence of circulating tumor cells or minimal residual disease after colon cancer surgery. A total of 60 patients who underwent radical colon cancer surgery were enrolled in this prospective, randomized, two-center study. Patients were randomized into three groups, namely piritramide, morphine and postoperative epidural analgesia. We evaluated the presence of carcinoembryonic antigen (CEA) and cytokeratin 20 (CK-20) mRNA positive circulating tumor cells in peripheral blood before surgery, immediately after surgery, on postoperative day two and one month after surgery. The presence of circulating tumor cells was assessed by quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR). In the priritramide postoperative analgesia group, the presence of CEA mRNA positive cells was significantly lower on a postoperative day two compared to the other groups (p=0.04). The value of CK-20 mRNA positive cells was the same in all groups on all days. In all groups, both types of circulating tumor cells returned to normal levels one month after surgery. Demographic and baseline clinical characteristics were similar in all groups. Compared with morphine and epidural analgesia, piritramide significantly reduces the amount of CEA mRNA positive circulating tumor cells after radical colon cancer surgery.

Keywords: cancer progression, colon cancer, minimal residual disease, perioperative analgesia.

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Authors: Hossein Barri Ghazani

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Transfusion-related acute lung injury is the main reason of transfusion-related death, and it’s assigned to white blood cell reactive antibodies present in the blood product (anti-HLA class I and class II or anti granulocyte antibodies). TRALI may occur in the COVID-19 patients who are treated by convalescent plasma. The rate of TRALI’s reactions is the same in both males and females and can happen in all age groups. TRALI’s occurrence is higher for people who receive plasma from female donors because the parous female donors have multiple HLA antibodies in their plasma. Patients with chronic liver disease have an augmented risk of transfusion-related acute lung injuries from plasma containing blood products like FFP and PRP. The condition of TRALI suddenly starts with a non‐cardiogenic pulmonary Edema, often accompanied by marked systemic hypovolemic and hypotension. The conditions occur during or within a few hours of transfusion. Chest X-ray shows a nodular penetration or bats’ wing pattern of Edema which can be seen in acute respiratory distress syndrome as well. TRALI can occur with any type of blood products and can occur with as little as one unit. The blood donor center should be informed of the suspected TRALI reactions when the symptoms of TRALI are observed. After a review of the clinical data, the donors must be screened for granulocyte and HLA antibodies. The diagnosis and management of TRALI is not simple and is best done with a professional team and a specialty skilled nurse experienced with the upkeep of these patients.

Keywords: TRALI, transfusion-related death, anti-granulocyte antibodies, anti-HLA antibodies, COVID-19

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Authors: Helen Zhang

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Accurate segmentation of the airways from CT scans is crucial for early diagnosis of lung cancer. However, the existing airway segmentation algorithms often rely on thin-slice CT scans, which can be inconvenient and costly. This paper presents a set of machine learning-based 3D super-resolution algorithms along heterogeneous dimensions to improve the resolution of thicker CT scans to reduce the reliance on thin-slice scans. To evaluate the efficacy of the super-resolution algorithms, quantitative assessments using PSNR (Peak Signal to Noise Ratio) and SSIM (Structural SIMilarity index) were performed. The impact of super-resolution on airway segmentation accuracy is also studied. The proposed approach has the potential to make airway segmentation more accessible and affordable, thereby facilitating early diagnosis and treatment of lung cancer.

Keywords: 3D super-resolution, airway segmentation, thin-slice CT scans, machine learning

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Authors: Gabriele Ciasca, Tanya E. Sassun, Eleonora Minelli, Manila Antonelli, Massimiliano Papi, Antonio Santoro, Felice Giangaspero, Roberto Delfini, Marco De Spirito

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Glioblastoma multiforme (GBM) is an extremely aggressive brain tumor, characterized by a diffuse infiltration of neoplastic cells into the brain parenchyma. Although rarely considered, mechanical cues play a key role in the infiltration process that is extensively mediated by the tumor microenvironment stiffness and, more in general, by the occurrence of aberrant interactions between neoplastic cells and the extracellular matrix (ECM). Here we provide a nano-mechanical characterization of the viscoelastic response of human GBM tissues by indentation-type atomic force microscopy. High-resolution elasticity maps show a large difference between the biomechanics of GBM tissues and the healthy peritumoral regions, opening possibilities to optimize the tumor resection area. Moreover, we unveil the nanomechanical signature of necrotic regions and anomalous vasculature, that are two major hallmarks useful for glioma staging. Actually, the morphological grading of GBM relies mainly on histopathological findings that make extensive use of qualitative parameters. Our findings have the potential to positively impact on the development of novel quantitative methods to assess the tumor grade, which can be used in combination with conventional histopathological examinations. In order to provide a more in-depth description of the role of mechanical cues in tumor progression, we compared the nano-mechanical fingerprint of GBM tissues with that of grade-I (WHO) meningioma, a benign lesion characterized by a completely different growth pathway with the respect to GBM, that, in turn hints at a completely different role of the biomechanical interactions.

Keywords: AFM, nano-mechanics, nanomedicine, brain tumors, glioblastoma

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Authors: Shoukat Ali, Amjad Hussain, Latif-ur-Rehman, Sehrish Inam

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Radiotherapy plays an important role in the management of cancer patients. Approximately 50% of the cancer patients receive radiotherapy at one point or another during the course of treatment. The entire radiotherapy treatment of curative intent is divided into different phases, depending on the histology of the tumor. The established protocols are useful in deciding the total dose, fraction size, and numbers of phases. The objective of this study was to evaluate the dosimetric differences between the conventional treatment protocols and the three-dimensional conformal simultaneously integrated boost (SIB) plans for three different tumors sites (i.e. bladder, breast, and brain). A total of 30 patients with brain, breast and bladder cancers were selected in this retrospective study. All the patients were CT simulated initially. The primary physician contoured PTV1 and PTV2 in the axial slices. The conventional doses prescribed for brain and breast is 60Gy/30 fractions, and 64.8Gy/36 fractions for bladder treatment. For the SIB plans biological effective doses (BED) were calculated for 25 fractions. The two conventional (Phase I and Phase II) and a single SIB plan for each patient were generated on Eclipse™ treatment planning system. Treatment plans were compared and analyzed for coverage index, conformity index, homogeneity index, dose gradient and organs at risk doses.In both plans 95% of PTV volume received a minimum of 95% of the prescribe dose. Dose deviation in the optic chiasm was found to be less than 0.5%. There is no significant difference in lung V20 and heart V30 in the breast plans. In the rectum plans V75%, V50% and V25% were found to be less than 1.2% different. Deviation in the tumor coverage, conformity and homogeneity indices were found to be less than 1%. SIB plans with three dimensional conformal radiotherapy technique reduce the overall treatment time without compromising the target coverage and without increasing dose to the organs at risk. The higher dose per fraction may increase the late effects to some extent. Further studies are required to evaluate the late effects with the intention of standardizing the SIB technique for practical implementation.

Keywords: coverage index, conformity index, dose gradient, homogeneity index, simultaneously integrated boost

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Authors: Ranjot Kaur, Om P. Katare, Anupama Sharma, Sarah R. Dennison, Kamalinder K. Singh, Bhupinder Singh

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Respiratory microbial infections being among the top leading cause of death worldwide are difficult to treat as the microbes reside deep inside the airways, where only a small fraction of drug can access after traditional oral or parenteral routes. As a result, high doses of drugs are required to maintain drug levels above minimum inhibitory concentrations (MIC) at the infection site, unfortunately leading to severe systemic side-effects. Therefore, delivering antimicrobials directly to the respiratory tract provides an attractive way out in such situations. In this context, current study embarks on the systematic development of lung lia pid-modified chitosan nanoparticles for inhalation of voriconazole. Following the principles of quality by design, the chitosan nanoparticles were prepared by ionic gelation method and further coated with major lung lipid by precipitation method. The factor screening studies were performed by fractional factorial design, followed by optimization of the nanoparticles by Box-Behnken Design. The optimized formulation has a particle size range of 170-180nm, PDI 0.3-0.4, zeta potential 14-17, entrapment efficiency 45-50% and drug loading of 3-5%. The presence of a lipid coating was confirmed by FESEM, FTIR, and X-RD. Furthermore, the nanoparticles were found to be safe upto 40µg/ml on A549 and Calu-3 cell lines. The quantitative and qualitative uptake studies also revealed the uptake of nanoparticles in lung epithelial cells. Moreover, the data from Spraytec and next-generation impactor studies confirmed the deposition of nanoparticles in lower airways. Also, the interaction of nanoparticles with DPPC monolayers signifies its biocompatibility with lungs. Overall, the study describes the methodology and potential of lipid-coated chitosan nanoparticles in futuristic inhalation nanomedicine for the management of pulmonary aspergillosis.

Keywords: dipalmitoylphosphatidylcholine, nebulization, DPPC monolayers, quality-by-design

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Authors: Ieva Bruzauskaite, Jovile Raudoniute, Karina Poliakovaite, Danguole Zabulyte, Daiva Bironaite, Ruta Aldonyte

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Introduction: Air pollution is a growing global problem which has been shown to be responsible for various adverse health outcomes. Immunotoxicity, such as dysregulated inflammation, has been proposed as one of the main mechanisms in air pollution-associated diseases. Chronic obstructive pulmonary disease (COPD) is among major morbidity and mortality causes worldwide and is characterized by persistent airflow limitation caused by the small airways disease (obstructive bronchiolitis) and irreversible parenchymal destruction (emphysema). Exact pathways explaining the air pollution induced and mediated disease states are still not clear. However, modern societies understand dangers of polluted air, seek to mitigate such effects and are in need for reliable biomarkers of air pollution. We hypothesise that post-translational modifications of structural proteins, e.g. citrullination, might be a good candidate biomarker. Thus, we have designed this study, where mice were exposed to diesel exhaust and the ongoing protein modifications and inflammation in lungs and other tissues were assessed. Materials And Methods: To assess the effects of diesel exhaust a in vivo study was designed. Mice (n=10) were subjected to everyday 2-hour exposure to diesel exhaust for 14 days. Control mice were treated the same way without diesel exhaust. The effects within lung and other tissues were assessed by immunohistochemistry of formalin-fixed and paraffin-embedded tissues. Levels of inflammation and citrullination related markers were investigated. Levels of parenchymal damage were also measured. Results: In vivo study corroborates our own data from in vitro and reveals diesel exhaust initiated inflammatory shift and modulation of lung peptidyl arginine deiminase 4 (PAD4), citrullination associated enzyme, levels. In addition, high levels of citrulline were observed in exposed lung tissue sections co-localising with increased parenchymal destruction. Conclusions: Subacute exposure to diesel exhaust renders mice lungs inflammatory and modifies certain structural proteins. Such structural changes of proteins may pave a pathways to lost/gain function of affected molecules and also propagate autoimmune processes within the lung and systemically.

Keywords: air pollution, citrullination, in vivo, lungs

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Authors: Rasmila Kawan, Sanjay Juvekar, Sandeep Salvi, Gufran Beig, Rainer Sauerborn

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Background: Indoor air pollution especially from the use of biomass fuels, remains a potentially large global health threat. The inefficient use of such fuels in poorly ventilated conditions results in high levels of indoor air pollution, most seriously affecting women and young children. Objectives: The main aim of this study was to measure and compare the lung function of the women exposed in the biomass fuels and LPG fuels and relate it to the indoor emission measured using a structured questionnaire, spirometer and filter based low volume samplers respectively. Methodology: This cross-sectional comparative study was conducted among the women (aged > 18 years) living in rural villages of Pune district who were not diagnosed of chronic pulmonary diseases or any other respiratory diseases and using biomass fuels or LPG for cooking for a minimum period of 5 years or more. Data collection was done from April to June 2017 in dry season. Spirometer was performed using the portable, battery-operated ultrasound Easy One spirometer (Spiro bank II, NDD Medical Technologies, Zurich, Switzerland) to determine the lung function over Forced expiratory volume. The primary outcome variable was forced expiratory volume in 1 second (FEV1). Secondary outcome was chronic obstruction pulmonary disease (post bronchodilator FEV1/ Forced Vital Capacity (FVC) < 70%) as defined by the Global Initiative for Obstructive Lung Disease. Potential confounders such as age, height, weight, smoking history, occupation, educational status were considered. Results: Preliminary results showed that the lung function of the women using Biomass fuels (FEV1/FVC = 85% ± 5.13) had comparatively reduced lung function than the LPG users (FEV1/FVC = 86.40% ± 5.32). The mean PM 2.5 mass concentration in the biomass user’s kitchen was 274.34 ± 314.90 and 85.04 ± 97.82 in the LPG user’s kitchen. Black carbon amount was found higher in the biomass users (black carbon = 46.71 ± 46.59 µg/m³) than LPG users (black carbon=11.08 ± 22.97 µg/m³). Most of the houses used separate kitchen. Almost all the houses that used the clean fuel like LPG had minimum amount of the particulate matter 2.5 which might be due to the background pollution and cross ventilation from the houses using biomass fuels. Conclusions: Therefore, there is an urgent need to adopt various strategies to improve indoor air quality. There is a lacking of current state of climate active pollutants emission from different stove designs and identify major deficiencies that need to be tackled. Moreover, the advancement in research tools, measuring technique in particular, is critical for researchers in developing countries to improve their capability to study the emissions for addressing the growing climate change and public health concerns.

Keywords: black carbon, biomass fuels, indoor air pollution, lung function, particulate matter

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Authors: Regina M. Chiechio, Rémi Leguevél, Helene Solhi, Marie Madeleine Gueguen, Stephanie Dutertre, Xavier, Jean-Pierre Bazureau, Olivier Mignen, Pascale Even-Hernandez, Paolo Musumeci, Maria Jose Lo Faro, Valerie Marchi

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Thanks to their ultra-small size, high electron density, and low toxicity, gold nanoclusters (Au NCs) have unique photoelectrochemical and luminescence properties that make them very interesting for diagnosis bio-imaging and theranostics. These applications require control of their delivery and interaction with cells; for this reason, the surface chemistry of Au NCs is essential to determine their interaction with the targeted biological objects. Here we demonstrate their ability as markers of pancreatic tumor cells. By functionalizing the surface of the NCs with a recognition peptite (U11), the nanostructures are able to preferentially bind to pancreatic cancer cells via a receptor (uPAR) overexpressed by these cells. Furthermore, the NCs can mark even the nucleus without the need of fixing the cells. These nanostructures can therefore be used as a non-toxic, multivalent luminescent platform, capable of selectively recognizing tumor cells for bioimaging, drug delivery, and radiosensitization.

Keywords: gold nanoclusters, luminescence, biomarkers, pancreatic cancer, biomedical applications, bioimaging, fluorescent probes, drug delivery

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Authors: Drashti G. Daraji, Rosa E. Moo-Puc, Hitesh D. Patel

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Substituted 2-Thioimidazole analogues have been synthesized and confirmed by advanced spectroscopic techniques. Among them, ten compounds have been selected and evaluated for their in vitro anti-cancer activity at the National Cancer Institute (NCI) for testing against a panel of 60 different human tumor cell lines derived from nine neoplastic cancer types. Furthermore, synthesized compounds were tested for their in vitro antiprotozoal activity, and none of them exhibited significant potency against antiprotozoans. It was observed that the tested all compounds seem effective on the UACC-62 melanoma cancer cell line as compared to other cancer cell lines and also exhibited the least potent in the Non-Small Cell Lung Cancer cell line in one-dose screening. In silico studies of these derivatives were carried out by molecular docking techniques and Absorption, Distribution, Metabolism, and Excretion (ADME) using Schrödinger software to find potent B-Raf kinase inhibitor (PDB ID: 3OG7). All the compounds have been performed for docking study; Compound D4 has a good docking score for melanoma cancer as compared with other.

Keywords: anticancer activity, cancer cell line, 2-thio imidazole, one-dose assay, molecular docking

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Authors: Veronika Zivicova, Petr Broz, Zdenek Fik, Alzbeta Mifkova, Jan Plzak, Zdenek Cada, Herbert Kaltner, Jana Fialova Kucerova, Hans-Joachim Gabius, Karel Smetana Jr.

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The possibility to determine genome-wide expression profiles of cells and tissues opens a new level of analysis in the quest to define dysregulation in malignancy and thus identify new tumor markers. Toward this long-term aim, we here address two issues on this level for head and neck cancer specimen: i) defining profiles in different regions, i.e. the tumor, the transition zone and normal control and ii) comparing complete data sets for seven individual patients. Special focus in the flanking immunohistochemical part is given to adhesion/growth-regulatory galectins that upregulate chemo- and cytokine expression in an NF-κB-dependent manner, to these regulators and to markers of differentiation, i.e. keratins. The detailed listing of up- and down-regulations, also available in printed form (1), not only served to unveil new candidates for testing as marker but also let the impact of the tumor in the transition zone become apparent. The extent of interindividual variation raises a strong cautionary note on assuming uniformity of regulatory events, to be noted when considering therapeutic implications. Thus, a combination of test targets (and a network analysis for galectins and their downstream effectors) is (are) advised prior to reaching conclusions on further perspectives.

Keywords: galectins, genome scale sequencing, squamous cell carcinoma, transition zone

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Authors: Subodh Kumar, Sanjeev Kumar Sharma, Gaurav Kaushik, Pramod Avti, Phulen Sarma, Bikash Medhi, Krishan Lal Khanduja

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Background: It is well known that cigarette smoke is one of the causative factors in various lung diseases especially cancer. Carcinogens and oxidant molecules present in cigarette smoke not only damage the cellular constituents (lipids, proteins, DNA) but may also regulate the molecular pathways involved in inflammation and cancer. Continuous oxidative stress caused by the constituents of cigarette smoke leads to higher PhospholipaseA₂ (PLA₂) activity, resulting in elevated levels of secondary metabolites whose role is well defined in cancer. To reduce the burden of chronic inflammation as well as oxidative stress, and higher levels of secondary metabolites, we checked the curative potential of PLA₂ inhibitor Bromoenol Lactone (BEL) during continuous exposure of cigarette smoke condensate (CSC). Aim: To check the therapeutic potential of Bromoenol Lactone (BEL), an inhibitor of PhospholipaseA₂s, in pathways of CSC-induced changes in type I and type II alveolar epithelial cells. Methods: Effect of BEL on CSC-induced PLA2 activity were checked using colorimetric assay, cellular toxicity using cell viability assay, membrane integrity using fluorescein di-acetate (FDA) uptake assay, reactive oxygen species (ROS) levels and apoptosis markers through flow cytometry, and cellular regulation using MAPKinases levels, in lung epithelium. Results: BEL significantly mimicked CSC-induced PLA₂ activity, ROS levels, apoptosis, and kinases level whereas improved cellular viability and membrane integrity. Conclusions: Current observations revealed that BEL may be a potential therapeutic agent during Cigarette smoke-induced anomalies in lung epithelium.

Keywords: cigarette smoke condensate, phospholipase A₂, oxidative stress, alveolar epithelium, bromoenol lactone

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Authors: Mohammadreza Hedyehzadeh, Mahdi Yousefi

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Colon cancer is one of the most common cancer, which predicted to increase its prevalence due to the bad eating habits of peoples. Nowadays, due to the busyness of people, the use of fast foods is increasing, and therefore, diagnosis of this disease and its treatment are of particular importance. To determine the best treatment approach for each specific colon cancer patients, the oncologist should be known the stage of the tumor. The most common method to determine the tumor stage is TNM staging system. In this system, M indicates the presence of metastasis, N indicates the extent of spread to the lymph nodes, and T indicates the size of the tumor. It is clear that in order to determine all three of these parameters, an imaging method must be used, and the gold standard imaging protocols for this purpose are CT and PET/CT. In CT imaging, due to the use of X-rays, the risk of cancer and the absorbed dose of the patient is high, while in the PET/CT method, there is a lack of access to the device due to its high cost. Therefore, in this study, we aimed to estimate the tumor size and the extent of its spread to the lymph nodes using MR images. More than 1300 MR images collected from the TCIA portal, and in the first step (pre-processing), histogram equalization to improve image qualities and resizing to get the same image size was done. Two expert radiologists, which work more than 21 years on colon cancer cases, segmented the images and extracted the tumor region from the images. The next step is feature extraction from segmented images and then classify the data into three classes: T0N0، T3N1 و T3N2. In this article, the VGG-16 convolutional neural network has been used to perform both of the above-mentioned tasks, i.e., feature extraction and classification. This network has 13 convolution layers for feature extraction and three fully connected layers with the softmax activation function for classification. In order to validate the proposed method, the 10-fold cross validation method used in such a way that the data was randomly divided into three parts: training (70% of data), validation (10% of data) and the rest for testing. It is repeated 10 times, each time, the accuracy, sensitivity and specificity of the model are calculated and the average of ten repetitions is reported as the result. The accuracy, specificity and sensitivity of the proposed method for testing dataset was 89/09%, 95/8% and 96/4%. Compared to previous studies, using a safe imaging technique (MRI) and non-use of predefined hand-crafted imaging features to determine the stage of colon cancer patients are some of the study advantages.

Keywords: colon cancer, VGG-16, magnetic resonance imaging, tumor size, lymph node metastasis

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Authors: Melissa Hachem, Maxime Loizeau, Nadine Saleh, Isabelle Momas, Lynda Bensefa-Colas

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Professional drivers are exposed inside their vehicles to high levels of air pollutants due to the considerable time they spend close to motor vehicle emissions. Little is known about ultrafine particles (UFP) or black carbon (BC) adverse respiratory health effects compared to the regulated pollutants. We aimed to study the short-term associations between UFP and BC concentrations inside vehicles and (1) the onset of mucosal irritation and (2) the acute changes in lung function of Parisian taxi drivers during a working day. An epidemiological study was carried out on 50 taxi drivers in Paris. UFP and BC were measured inside their vehicles with DiSCmini® and microAeth®, respectively. On the same day, the frequency and the severity of nose, eye, and throat irritations were self-reported by each participant and a spirometry test was performed before and after the work shift. Multivariate analysis was used to evaluate the associations between in-taxis UFP and BC concentrations and mucosal irritation and lung function, after adjustment for potential confounders. In-taxis UFP concentrations ranged from 17.9 to 37.9 × 103 particles/cm³ and BC concentrations from 2.2 to 3.9 μg/m³, during a mean of 9 ± 2 working hours. Significant dose-response relationships were observed between in-taxis UFP concentrations and both nasal irritation and lung function. The increase of in-taxis UFP (for an interquartile range of 20 × 103 particles/cm3) was associated to an increase in nasal irritation (adjusted OR = 6.27 [95% CI: 1.02 to 38.62]) and to a reduction in forced expiratory flow at 25–75% by −7.44% [95% CI: −12.63 to −2.24], forced expiratory volume in one second by −4.46% [95% CI: −6.99 to −1.93] and forced vital capacity by −3.31% [95% CI: −5.82 to −0.80]. Such associations were not found with BC. Incident throat and eye irritations were not related to in-vehicle particles exposure; however, they were associated with outdoor air quality (estimated by the Atmo index) and in-vehicle humidity, respectively. This study is the first to show a significant association, within a short-period of time, between in-vehicle UFP exposure and acute respiratory effects in professional drivers.

Keywords: black carbon, lung function, mucosal irritation, taxi drivers, ultrafine particles

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Authors: L. M. Al-Harbi, A. M. Shokry, J. S. M. Sabir, A. Chaudhary, J. Manikandan, K. S. Saini

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Breast cancer is the second most common cause of cancer death worldwide and is the most common malignancy among Saudi females. During breast carcinogenesis, a wide-array of cytogenetic changes involving deletions, or amplification, or translocations, of part or whole of chromosome regions have been observed. Because of the limitations of various earlier technologies, newer tools are developed to scan for changes at the genomic level. Recently, Array Comparative Genomic Hybridization (aCGH) technique has been applied for detecting segmental genomic alterations at molecular level. In this study, aCGH was performed on twenty breast cancer tumors and their matching non-tumor (normal) counterparts using the Agilent 2x400K. Several regions were identified to be either amplified or deleted in a tumor-specific manner. Most frequent alterations were amplification of chromosome 1q, chromosome 8q, 20q, and deletions at 16q were also detected. The amplification of genetic events at 1q and 8q were further validated using FISH analysis using probes targeting 1q25 and 8q (MYC gene). The copy number changes at these loci can potentially cause a significant change in the tumor behavior, as deletions in the E-Cadherin (CDH1)-tumor suppressor gene as well as amplification of the oncogenes-Aurora Kinase A. (AURKA) and MYC could make these tumors highly metastatic. This study validates the use of aCGH in Saudi breast cancer patients and sets the foundations necessary for performing larger cohort studies searching for ethnicity-specific biomarkers and gene copy number variations.

Keywords: breast cancer, molecular biology, ecology, environment

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Authors: Luiz Carlos Wrobel, Matjaz Hribersek, Jure Marn, Jurij Iljaz

Abstract:

Dynamic thermography has been clinically proven to be a valuable diagnostic technique for skin tumor detection as well as for other medical applications such as breast cancer diagnostics, diagnostics of vascular diseases, fever screening, dermatological and other applications. Thermography for medical screening can be done in two different ways, observing the temperature response under steady-state conditions (passive or static thermography), and by inducing thermal stresses by cooling or heating the observed tissue and measuring the thermal response during the recovery phase (active or dynamic thermography). The numerical modelling of heat transfer phenomena in biological tissue during dynamic thermography can aid the technique by improving process parameters or by estimating unknown tissue parameters based on measured data. This paper presents a nonlinear numerical model of multilayer skin tissue containing a skin tumor, together with the thermoregulation response of the tissue during the cooling-rewarming processes of dynamic thermography. The model is based on the Pennes bioheat equation and solved numerically by using a subdomain boundary element method which treats the problem as axisymmetric. The paper includes computational tests and numerical results for Clark II and Clark IV tumors, comparing the models using constant and temperature-dependent thermophysical properties, which showed noticeable differences and highlighted the importance of using a local thermoregulation model.

Keywords: boundary element method, dynamic thermography, static thermography, skin tumor diagnostic

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Authors: Anna Cameron, Chunxia Zhao, Haofei Wang, Yun Liu, Guang Ze Yang

Abstract:

Since the first publication in 1775, cancer research has built a comprehensive understanding of how cellular components of the tumor niche promote disease development. However, only within the last decade has research begun to establish the impact of non-cellular components of the niche, particularly the extracellular matrix (ECM). The ECM, a three-dimensional scaffold that sustains the tumor microenvironment, plays a crucial role in disease progression. Cancer cells actively deregulate and remodel the ECM to establish a tumor-promoting environment. Recent work has highlighted the need to further our understanding of the complexity of this cancer-ECM relationship. In vitro models use hydrogels to mimic the ECM, as hydrogel matrices offer biological compatibility and stability needed for long term cell culture. However, natural hydrogels are being used in these models verbatim, without tuning their biophysical characteristics to achieve pathophysiological relevance, thus limiting their broad use within cancer research. The biophysical attributes of these gels dictate cancer cell proliferation, invasion, metastasis, and therapeutic response. Evaluating the three most widely used natural hydrogels, Matrigel, collagen, and agarose gel, the permeability, stiffness, and pore-size of each gel were measured and compared to the in vivo environment. The pore size of all three gels fell between 0.5-6 µm, which coincides with the 0.1-5 µm in vivo pore size found in the literature. However, the stiffness for hydrogels able to support cell culture ranged between 0.05 and 0.3 kPa, which falls outside the range of 0.3-20,000 kPa reported in the literature for an in vivo ECM. Permeability was ~100x greater than in vivo measurements, due in large part to the lack of cellular components which impede permeation. Though, these measurements prove important when assessing therapeutic particle delivery, as the ECM permeability decreased with increasing particle size, with 100 nm particles exhibiting a fifth of the permeability of 10 nm particles. This work explores ways of adjusting the biophysical characteristics of hydrogels by changing protein concentration and the trade-off, which occurs due to the interdependence of these factors. The global aim of this work is to produce a more pathophysiologically relevant model for each tumor type.

Keywords: cancer, extracellular matrix, hydrogel, microfluidic

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Authors: Neda Menbari, Ramin Mehdiabadi

Abstract:

Background: breast cancer remains a critical global health issue, constituting a leading cause of cancer-related mortality in women. MicroRNAs (miRs) are natural RNA molecules that play an important role in cellular processes and regulate post-transcriptional gene expression. MiR-216b-5p is a miR that acts as a tumor suppressor. The expression levels of FoxM1 and miR-216b-5p in malignant and control cells have been evaluated by quantitative polymerase chain reaction (qPCR) technique and flow cytometry. Results: the results of this study revealed a significant downregulation of miR-216b-5p in cancerous cells compared to the control MCF-10A cells (P=0.0004). Interestingly, the expression of miR-216b-5p exhibited an inverse relationship with key clinical indicators such as tumor size, grade, and lymph node invasion. Conclusion: The study's findings showed the prognostic value of miR-216b-5p levels in breast cancer, and its reduced expression correlates with unfavorable tumor characteristics. This research recommends performing more studies on the role of FoxM1 and miR-216b-5p in breast cancer pathology which potentially paving the way for targeted therapeutic interventions.

Keywords: breast cancer, gene expression, FOXM1, microRNA

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Authors: Behrooz Nikahval, Mohammad Saeed Ahrari-Khafi, Sakineh Behroozpoor, Saeed Nazifi

Abstract:

Osteoarthritis (OA) is a progressive and degenerative condition of the articular cartilage and other joints’ structures. It is essential to diagnose this condition as early as possible. The present research was performed to measure the Osteoprotegrin (OPG) and Tumor Necrosis Factor α (TNF-α) in synovial fluid and blood serum of dogs with surgically transected cruciate ligament as a model of OA, to evaluate if measuring of these parameters can be used as a way of early diagnosis of OA. In the present study, four mature, clinically healthy dogs were selected to investigate the effect of experimental OA, on OPG and TNF-α as a way of early detection of OA. OPG and TNF-α were measured in synovial fluid and blood serum on days 0, 14, 28, 90 and 180 after surgical transaction of cranial cruciate ligament in one stifle joint. Statistical analysis of the results showed that there was a significant increase in TNF-α in both synovial fluid and blood serum. OPG showed a decrease two weeks after OA induction. However, it fluctuated afterward. In conclusion, TNF-α could be used in both synovial fluid and blood serum as a way of early detection of OA; however, further research still needs to be conducted on OPG values in OA detection.

Keywords: osteoarthritis, osteoprotegrin, tumor necrosis factor α, synovial fluid, serum, dog

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Authors: Abdul Matin, Muhammad Ajmal, Uzma Yunus, Noaman-ul Haq, Hafiz M. Shohaib, Ambreen G. Muazzam

Abstract:

Carbon nanoparticles (CNPs) have unique properties that are useful for the diagnosis and treatment of cancer due to their precise properties like small size (ideal for delivery within the body) stability in solvent and tunable surface chemistry for targeted delivery. Here, highly fluorescent, monodispersed and water-soluble CNPs were synthesized directly from a suitable carbohydrate source (glucose and sucrose) by one-step acid assisted ultrasonic treatment at 35 KHz for 4 hours. This method is green, simple, rapid and economical and can be used for large scale production and applications. The average particle sizes of CNPs are less than 10nm and they emit bright and colorful green-blue fluorescence under the irradiation of UV-light at 365nm. The CNPs were characterized by scanning electron microscopy, fluorescent spectrophotometry, Fourier transform infrared spectrophotometry, ultraviolet-visible spectrophotometry and TGA analysis. Fluorescent CNPs were used as fluorescent probe and nano-carriers for anticancer drug. Functionalized CNPs (with ethylene diamine) were attached with anticancer drug-Methotrexate. In vitro bioactivity and biocompatibility of CNPs-drug conjugates was evaluated by LDH assay and Sulforhodamine B assay using human lung carcinoma cell lines (H157). Our results reveled that CNPs showed biocompatibility and CNPs-anticancer drug conjugates have shown potent cytotoxic effects and high antitumor activities in lung cancer cell lines. CNPs are proved to be excellent substitute for conventional drug delivery cargo systems and anticancer therapeutics in vitro. Our future studies will be more focused on using the same nanoparticles in vivo model system.

Keywords: carbon nanoparticles, carbon nanoparticles-methotrexate conjugates, human lung carcinoma cell lines, lactate dehydrogenase, methotrexate

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Authors: Mayssa Bensalah, Atef Boujelben, Mouna Baklouti, Mohamed Abid

Abstract:

Image segmentation has a fundamental role in analysis and interpretation for many applications. The automated segmentation of organs and tissues throughout the body using computed imaging has been rapidly increasing. Indeed, it represents one of the most important parts of clinical diagnostic tools. In this paper, we discuss a thorough literature review of recent methods of tumour segmentation from medical images which are briefly explained with the recent contribution of various researchers. This study was followed by comparing these methods in order to define new directions to develop and improve the performance of the segmentation of the tumour area from medical images.

Keywords: features extraction, image segmentation, medical images, tumor detection

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Authors: Vinaya Kambappa, Chinnadurai Mani, Komaraiah Palle

Abstract:

Non-small cell-lung cancer (NSCLC) cells have increased expression of EGFR, which makes them a potential target for cancer therapy. Based on molecular docking and previous reports, we designed and synthesized quinazoline derivatives as potent EGFR inhibitors. Among the derivatives, three compounds showed good antiproliferative activity against A-549 and H-1299 cells. Furthermore, these compounds inhibited EGFR signaling exhibiting diminishing p-EGFR and its downstream proteins like p-Akt, p-Erk1/2, and p-mTOR; however, it did not alter the levels of EGFR, Akt, Erk1/2 and mTOR proteins. Flow cytometric analysis indicated the accumulation of cells at G1 phase suggesting induction of apoptosis, which was further confirmed by annexin V/propidium iodide staining. Our study suggested that quinazoline scaffold can be developed as novel EGFR kinase inhibitors for cancer therapy.

Keywords: apoptosis, non-small cell-lung cancer cells, EGFR, quinazoline

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Authors: S. T. Kumbhar, M. S. Bhatia, R. C. Khairate

Abstract:

An effective nanodrug delivery system was developed by using chitosan for increased encapsulation efficiency and retarded release of curcumin. Potential ionotropic gelation method was used for the development of chitosan nanoparticles with TPP as cross-linker. The characterization was done for analysis of size, structure, surface morphology, and thermal behavior of synthesized chitosan nanoparticles. The encapsulation efficiency was more than 80%, with improved drug loading capacity. The in-vitro drug release study showed that curcumin release rate was decreased significantly. These chitosan nanoparticles could be a suitable platform for co-delivery of curcumin and anticancer agent for enhanced cytotoxic effect on tumor cells.

Keywords: Curcumin, chitosan, nanoparticles, anticancer activity

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Authors: Siva Chander Chabattula, Piyush Kumar Gupta, Debashis Chakraborty, Rama Shanker Verma

Abstract:

Green nanoparticles have gotten a lot of attention because of their potential applications in tissue regeneration, bioimaging, wound healing, and cancer therapy. The physical and chemical methods to synthesize metal oxide nanoparticles have an environmental impact, necessitating the development of an environmentally friendly green strategy for nanoparticle synthesis. In this study, we used Annona muricata plant leaf extract to synthesize Zinc Oxide nanoparticles (Am-ZnO NPs), which were evaluated using UV/Visible spectroscopy, FTIR spectroscopy, X-Ray Diffraction, DLS, and Zeta potential. Nanoparticles had an optical absorbance of 355 nm and a net negative surface charge of ~ - 2.59 mV. Transmission Electron Microscope characterizes the Shape and size of the nanoparticles. The obtained Am-ZnO NPs are biocompatible and hemocompatible in nature. These nanoparticles caused an anti-cancer therapeutic effect in MIA PaCa2 and MOLT4 cancer cells by inducing oxidative stress, and a change in mitochondrial membrane potential leads to programmed cell death. Further, we observed a reduction in the size of lung cancer spheroids (act as tumor micro-environment) with doxorubicin as a positive control.

Keywords: Biomaterials, nanoparticle, anticancer activity, ZnO nanoparticles

Procedia PDF Downloads 167