Search results for: allogeneic hematopoietic stem cell transplantation
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 4295

Search results for: allogeneic hematopoietic stem cell transplantation

3365 Direct Organogenesis of Begonia Rex cv. DS-EYWA, An Unique Rare Cultivar, via Thin Cell Layering (TCL) Technique

Authors: Mahboubeh Davoudi Pahnekolayi

Abstract:

Begonia rex cv. DS-EYWA is a rare, unique cultivar of begonia rex with curly colorful leaves. Optimization of an in vitro efficient regeneration protocol by focusing on transverse Thin Cell Layer (tTCL) petiole explants for high-scale production of such a beautiful cultivar was considered as our main purpose in this experiment. Thus, various concentrations of Plant Growth Regulators (PGRs) including 6-Benzylaminopurine (BAP), Thidiazuron (TDY), and –Naphthaleneacetic Acid (NAA), were selected in a Completely Randomized Design (CRD) to establish and optimize the direct organogenesis efficiency of this cultivar. Cultivation of 1 mm tTCL petiole explants in noted treatments showed that 1.5 mgl-1 BAP + 0.5 mgl-1 NAA can induce the highest number of direct regenerated shoots and lower concentration of BAP (0.5 mgl-1) can be suggested for shoot elongation before rooting stage. Elongated shoots were successfully rooted in MS free basal medium and acclimatized in 1:1 peat moss: perlite sterilized pot mixture.

Keywords: begonia rare cultivar, direct organogenesis, explant type, regeneration, thin cell layering (TCL)

Procedia PDF Downloads 77
3364 The Development of Noctiluca scintillans Algal Bloom in Coastal Waters of Muscat, Sulanate of Oman

Authors: Aysha Al Sha'aibi

Abstract:

Algal blooms of the dinoflagellate species Noctiluca scintillans became frequent events in Omani waters. The current study aims at elucidating the abundance, size variation and observations on the feeding mechanism performed by this species during the winter bloom. An attempt was made, to relate observed biological parameters of the Noctiluca population to environmental factors. Field studies spanned the period from December 2014 to April 2015. Samples were collected from Bandar Rawdah (Muscat region) by Bongo nets, twice per week, from the surface and the integrated upper mixed layer. The measured environmental variables were: temperature, salinity, dissolved oxygen, chlorophyll a, turbidity, nitrite, phosphate, wind speed and rainfall. During the winter bloom (from December 2014 through February 2015), the abundance exhibited the highest concentration on 17 February (640.24×106 cell.L-1) in oblique samples and 83.9x103 cell.L-1 in surface samples, with a subsequent decline up to the end of April. The average number of food vacuoles inside Noctiluca cells was 1.5 per cell; the percentage of feeding Noctiluca compared to the entire population varied from 0.01% to 0.03%. Both the surface area of the Noctiluca symbionts (Pedinomonas noctilucae) and cell diameter were maximal in December. In oblique samples the highest average cell diameter and the surface area of symbiont algae were 751.7 µm and 179.2x103 µm2 respectively. In surface samples, highest average cell diameter and the surface area of symbionts were 760 µm and 284.05x103 µm2 respectively. No significant correlations were detected between Noctiluca’s biological parameters and environmental variables except for the correlation between cell diameter and chlorophyll a, also between symbiotic algae surface area and chlorophyll a. The high correlation of chlorophyll a was as a reason of endosymbiotic algae Pedinomonas noctilucae and green Noctiluca enhanced chlorophyll during bloom. All correlations among biological parameters were significant; they are perhaps one of major factors that mediating high growth rates, generating millions of cell per liter in a short time range. The results gained from this study will provide a beneficial background for understanding deeply the development of coastal algal blooms of Noctiluca scintillans. Moreover, results could be used in different applications related to marine environment.

Keywords: abundance, feeding activities, Noctiluca scintillans, Oman

Procedia PDF Downloads 440
3363 Metastatic Esophageal Squamous Cell Carcinoma Presenting with COVID-19 Infection and Cardiac Tamponade

Authors: Sutinon Yuchomsuk, Satchachon Changthom, Pruet Areesawangvong, Monsiri Jinapen

Abstract:

Background: Esophageal squamous cell carcinoma can be presented with many symptoms, such as dysphagia or weight loss. However, in some circumstances, rare presentations can be found, e.g., dyspnea, which is more common in pulmonary malignancy. And dyspnea is also one of the most common presentations of COVID-19 infection. So, in this case, we can learn from many points in patient symptoms and findings leading to the diagnosis of esophageal squamous cell carcinoma. Method: This research is a case-report study including one patient from Mahasarakham Hospital, Thailand. Data were collected during December 2021. Result: A 55-year-old Thai male patient with an unknown past medical history presented with dyspnea and shortness of breath for the duration of three days prior to admission. His symptom also included cough, fever, and sore throat. Laboratory results indicated that the patient had COVID-19 pneumonia. Further investigation showed that he had cardiac tamponade and suspected pulmonary/esophageal cancer. Lung biopsy and pericardiocentesis were done, which were positive for carcinoma from pericardial effusion but negative for malignancy from the lung biopsy. Later esophagogastroduodenoscopy was done with endoscopic tissue biopsy; the result was positive for squamous cell carcinoma of the esophagus. Conclusion: Most commonly, esophageal cancer is presented with dysphagia or weight loss. However, in some rare cases, patients can also be presented with dyspnea due to cardiac tamponade. And in recent years, COVID-19 has become a pandemic all over the world, sometimes masking symptoms of other diseases. Such as in this case, the patient didn’t improve after the pneumonia was resolved, which led to the final diagnosis of metastatic esophageal cancer.

Keywords: esophageal cancer, cardiac tamponade, metastatic squamous cell carcinoma, COVID-19 infection

Procedia PDF Downloads 125
3362 Knee Pain Reduction: Holistic vs. Traditional

Authors: Renee Moten

Abstract:

Introduction: Knee pain becomes chronic because the therapy used focuses only on the symptoms of knee pain and not the causes of knee pain. Preventing knee injuries is not in the toolbox of the traditional practitioner. This research was done to show that we must reduce the inflammation (holistically), reduce the swelling and regain flexibility before considering any type of exercise. This method of performing the correct exercise stops the bowing of the knee, corrects the walking gait, and starts to relieve knee, hip, back, and shoulder pain. Method: The holistic method that is used to heal knees is called the Knee Pain Recipe. It’s a six step system that only uses alternative medicine methods to reduce, relieve and restore knee joint mobility. The system is low cost, with no hospital bills, no physical therapy, and no painkillers that can cause damage to the kidneys and liver. This method has been tested on 200 women with knee, back, hip, and shoulder pain. Results: All 200 women reduce their knee pain by 50%, some by as much as 90%. Learning about ankle and foot flexibility, along with understanding the kinetic chain, helps improve the walking gait, which takes the pressure off the knee, hip and back. The knee pain recipe also has helped to reduce the need for a cortisone injection, stem cell procedures, to take painkillers, and surgeries. What has also been noted in the research was that if the women's knees were too far gone, the Knee Pain Recipe helped prepare the women for knee replacement surgery. Conclusion: It is believed that the Knee Pain Recipe, when performed by men and women from around the world, will give them a holistic alternative to drugs, injections, and surgeries.

Keywords: knee, surgery, healing, holistic

Procedia PDF Downloads 80
3361 Macular Ganglion Cell Inner Plexiform Layer Thinning

Authors: Hye-Young Shin, Chan Kee Park

Abstract:

Background: To compare the thinning patterns of the ganglion cell-inner plexiform layer (GCIPL) and peripapillary retinal nerve fiber layer (pRNFL) as measured using Cirrus high-definition optical coherence tomography (HD-OCT) in patients with visual field (VF) defects that respect the vertical meridian. Methods: Twenty eyes of eleven patients with VF defects that respect the vertical meridian were enrolled retrospectively. The thicknesses of the macular GCIPL and pRNFL were measured using Cirrus HD-OCT. The 5% and 1% thinning area index (TAI) was calculated as the proportion of abnormally thin sectors at the 5% and 1% probability level within the area corresponding to the affected VF. The 5% and 1% TAI were compared between the GCIPL and pRNFL measurements. Results: The color-coded GCIPL deviation map showed a characteristic vertical thinning pattern of the GCIPL, which is also seen in the VF of patients with brain lesions. The 5% and 1% TAI were significantly higher in the GCIPL measurements than in the pRNFL measurements (all P < 0.01). Conclusions: Macular GCIPL analysis clearly visualized a characteristic topographic pattern of retinal ganglion cell (RGC) loss in patients with VF defects that respect the vertical meridian, unlike pRNFL measurements. Macular GCIPL measurements provide more valuable information than pRNFL measurements for detecting the loss of RGCs in patients with retrograde degeneration of the optic nerve fibers.

Keywords: brain lesion, macular ganglion cell, inner plexiform layer, spectral-domain optical coherence tomography

Procedia PDF Downloads 339
3360 Binding Studies of Complexes of Anticancer Drugs with DNA and Enzymes Involved in DNA Replication Using Molecular Docking and Cell Culture Techniques

Authors: Fouzia Perveen, Rumana Qureshi

Abstract:

The presently studied twelve anticancer drugs are the cytotoxic agents which inhibit the replication of DNA and activity of enzymes involved in DNA replication namely topoisomerase-II, polymerase and helicase and have shown remarkable anticancer activity in clinical trials. In this study, we performed molecular docking studies of twelve antitumor drugs against DNA and DNA enzymes in the presence and absence of ascorbic acid (AA) and developed the quantitative structure-activity relationship (QSAR) model for anticancer activity screening. A number of electronic and steric descriptors were calculated using MOE software package. QSAR was established showing a correlation of binding strength with various physicochemical descriptors. Out of these twelve, eight cytotoxic drugs were tested on Non-Small Cell Lung Cancer cell lines (H-157 and H-1299) in the absence and presence of ascorbic acid and experimental IC50 values were calculated. From the docking studies, binding constants were calculated indicating the strength of drug-DNA and drug-enzyme complex formation and it was correlated to the IC50 values (both experimental and theoretical). These results can offer useful references for directing the molecular design of DNA enzyme inhibitor with improved anticancer activity.

Keywords: ascorbic acid, binding constant, cytotoxic agents, cell culture, DNA, DNA enzymes, molecular docking

Procedia PDF Downloads 433
3359 Comet Assay: A Promising Tool for the Risk Assessment and Clinical Management of Head and Neck Tumors

Authors: Sarim Ahmad

Abstract:

The Single Cell Gel Electrophoresis Assay (SCGE, known as comet assay) is a potential, uncomplicated, sensitive and state-of-the-art technique for quantitating DNA damage at individual cell level and repair from in vivo and in vitro samples of eukaryotic cells and some prokaryotic cells, being popular in its widespread use in various areas including human biomonitoring, genotoxicology, ecological monitoring and as a tool for research into DNA damage or repair in different cell types in response to a range of DNA damaging agents, cancer risk and therapy. The method involves the encapsulation of cells in a low-melting-point agarose suspension, lysis of the cells in neutral or alkaline (pH > 13) conditions, and electrophoresis of the suspended lysed cells, resulting in structures resembling comets as observed by fluorescence microscopy; the intensity of the comet tail relative to the head reflects the number of DNA breaks. The likely basis for this is that loops containing a break lose their supercoiling and become free to extend towards the anode. This is followed by visual analysis with staining of DNA and calculating fluorescence to determine the extent of DNA damage. This can be performed by manual scoring or automatically by imaging software. The assay can, therefore, predict an individual’s tumor sensitivity to radiation and various chemotherapeutic drugs and further assess the oxidative stress within tumors and to detect the extent of DNA damage in various cancerous and precancerous lesions of oral cavity.

Keywords: comet assay, single cell gel electrophoresis, DNA damage, early detection test

Procedia PDF Downloads 293
3358 Esophageal Premalignant and Malignant Epithelial Lesions: Pathological Characteristics and Value of Cyclooxygenase-2 Expression.

Authors: Hanan Mohamed Abd Elmoneim, Rawan Saleh AlJawi, Razan Saleh AlJawi, Aseel Abdullah AlMasoudi , Zyad Adnan Turkistani, Anas Abdulkarim Alkhoutani , Ohood Musaed AlJuhani , Hanan Attiyah AlZahrani

Abstract:

Background Esophageal cancer is the eighth most common cancer worldwide. More than 90% of esophageal cancers are either squamous cell carcinoma or adenocarcinoma. Squamous dysplasia is a precancerous lesion for squamous cell carcinoma and Barrett's esophagus is the precancerous lesion for adenocarcinoma. Gastro-esophageal reflux disease (GERD) is the initiation factor for Barrett's esophagus. Cyclooxygenase-2 (COX-2) is a key enzyme in arachidonic metabolism. It appears to play an important role in gastrointestinal carcinogenesis. COX-2 activity may be a potential target for the prevention of cancer progression by selective COX-2 inhibitors, which decrease proliferation and increase apoptosis. Objectives To assess COX-2 expression in premalignant and malignant esophageal epitheliums changes and detect its roles in progression of these lesions. Materials and Methods We analyzed the expression of COX-2 immunohistochemically in 40 esophageal biopsies utilizing the streptavidin-biotin-peroxidase complex method on archival formalin fixed-paraffin embedded blocks. Histopathologically, 17 (42.5%) of cases were non-malignant cases which included GERD, Barrett's esophagus and squamous dysplasia. The malignant cases were 23 (57.5%) squamous cell carcinoma, adenocarcinoma and undifferentiated carcinoma. Results In non-malignant cases 7 (41.2%) out of 17 cases had high COX-2 expression. In squamous cell carcinoma 10 (83.3%) out of 12 cases had high COX-2 expression. The expression of COX-2 was high in all 9 (100%) cases of adenocarcinoma. COX-2 expression is significantly increased (P=0.005 and P=0.0001) in squamous cell carcinoma and adenocarcinoma respectively. There was a significant difference in COX-2 immunoreactivity between malignant and non-malignant lesions (P=0.0003). Conclusion COX-2 is responsible for the progression of esophageal diseases from benign to malignant. We recommend that COX-2 immunohistochemistry should be done routinely for premalignant and malignant esophageal lesions as selective COX-2 inhibitors will be helpful in the treatment. Further studies on molecular and genetic basis of COX-2 expression are needed to unmask its role and relation to progression of esophageal lesions.

Keywords: Cox-2, Esophageal adinocarcinoma, Esophageal squamous cell carcinoma, Immunohistochemistry.

Procedia PDF Downloads 355
3357 New Quinazoline Derivative Induce Cytotoxic Effect against Mcf-7 Human Breast Cancer Cell

Authors: Maryam Zahedi Fard, Nazia Abdul Majid, Hapipah Mohd Ali, Mahmood Ameen Abdulla

Abstract:

New quinazoline schiff base 3-(5-bromo-2-hydroxy-3-methoxybenzylideneamino)-2-(5-bromo-2-hydroxy-3-methoxyphenyl)-2,3-dihydroquinazolin-4(1H)-one was investigated for anticancer activity against MCF-7 human breast cancer cell line with involved mechanism of apoptosis. The compound demonstrated a remarkable antiproliferative effect, with an IC50 value of 3.41 ± 0.34, after 72 hours of treatment. Morphological apoptotic features in treated MCF-7 cells were observed by AO/PI staining. Furthermore, treated MCF-7 cells subjected to apoptosis death, as exhibited by perturbation of mitochondrial membrane potential and cytochrome c release as well as increase in ROS generation. We also found activation of caspases 3/7 and -9. Moreover, acute toxicity test demonstrated the nontoxic nature of the compound in mice. Our results showed the selected compound significantly induce apoptosis in MCF-7 cells via intrinsic pathway, which might be considered as a potent candidate for further in vivo and clinical breast cancer studies.

Keywords: antiproliferative effect, MCF-7 human breast cancer cell line, apoptosis, caspases

Procedia PDF Downloads 535
3356 Vibration and Freeze-Thaw Cycling Tests on Fuel Cells for Automotive Applications

Authors: Gema M. Rodado, Jose M. Olavarrieta

Abstract:

Hydrogen fuel cell technologies have experienced a great boost in the last decades, significantly increasing the production of these devices for both stationary and portable (mainly automotive) applications; these are influenced by two main factors: environmental pollution and energy shortage. A fuel cell is an electrochemical device that converts chemical energy directly into electricity by using hydrogen and oxygen gases as reactive components and obtaining water and heat as byproducts of the chemical reaction. Fuel cells, specifically those of Proton Exchange Membrane (PEM) technology, are considered an alternative to internal combustion engines, mainly because of the low emissions they produce (almost zero), high efficiency and low operating temperatures (< 373 K). The introduction and use of fuel cells in the automotive market requires the development of standardized and validated procedures to test and evaluate their performance in different environmental conditions including vibrations and freeze-thaw cycles. These situations of vibration and extremely low/high temperatures can affect the physical integrity or even the excellent operation or performance of the fuel cell stack placed in a vehicle in circulation or in different climatic conditions. The main objective of this work is the development and validation of vibration and freeze-thaw cycling test procedures for fuel cell stacks that can be used in a vehicle in order to consolidate their safety, performance, and durability. In this context, different experimental tests were carried out at the facilities of the National Hydrogen Centre (CNH2). The experimental equipment used was: A vibration platform (shaker) for vibration test analysis on fuel cells in three axes directions with different vibration profiles. A walk-in climatic chamber to test the starting, operating, and stopping behavior of fuel cells under defined extreme conditions. A test station designed and developed by the CNH2 to test and characterize PEM fuel cell stacks up to 10 kWe. A 5 kWe PEM fuel cell stack in off-operation mode was used to carry out two independent experimental procedures. On the one hand, the fuel cell was subjected to a sinusoidal vibration test on the shaker in the three axes directions. It was defined by acceleration and amplitudes in the frequency range of 7 to 200 Hz for a total of three hours in each direction. On the other hand, the climatic chamber was used to simulate freeze-thaw cycles by defining a temperature range between +313 K and -243 K with an average relative humidity of 50% and a recommended ramp up and rump down of 1 K/min. The polarization curve and gas leakage rate were determined before and after the vibration and freeze-thaw tests at the fuel cell stack test station to evaluate the robustness of the stack. The results were very similar, which indicates that the tests did not affect the fuel cell stack structure and performance. The proposed procedures were verified and can be used as an initial point to perform other tests with different fuel cells.

Keywords: climatic chamber, freeze-thaw cycles, PEM fuel cell, shaker, vibration tests

Procedia PDF Downloads 119
3355 Growth and Morphological Characterization in Two Accessions of Sesame Plant

Authors: Ahmed Ibrahim Galadima, Abdullahi Muhammed Bello, Abdullateef Akintunde Raji, Ruqayyah Mujahidah Abdullateef, Hajara Sani Labaran

Abstract:

Sesamum indicium is an erect, herbaceous, branched, and warm-season annual crop. It differs in growth habit, form and shape, seed size and color, composition, size, and color of flowers. The experiments were performed by collecting two accessions of Sesamum indicum (white and black varieties). The morphological parameters like plant height and leaf size were measured using a ruler, while stem girth was observed using a vernier caliper. Germinability assessments were conducted by placing 100 seeds from each of the two sesame varieties and presoaked in 5 per cent sodium hypochlorite for 15 min., followed by rinse with distilled water. Germinability was assessed by placing the seeds in moist conditions and analyzing the outcome accordingly. The results from the experiments showed that the plant height (41.98 cm), stem girth (3.23 cm), and size of leaves (13.89 cm2) were higher in the white sesame variety when compared to the sesame black variety where 34.30 cm, 2.68 cm, and 7.47 cm2, respectively were obtained. But, from the black sesame variety, the number of leaves and the number of branches high values (105.06 cm) and (10.41), respectively were discovered. And significant differences were recorded in all the analyzed morphological parameters between the two sesame accessions, except stem girth. More so, the white variety of the sesame plant has demonstrated a good reproductive capability with the number of flowers (7.18), number of capsules (17.44), 100 seeds weight (1.67 g), and 1000 seeds weight (16.67 g). However, none of the analyzed reproductive parameters was observed from the black sesame variety. The white sesame variety was observed to have a higher number of Trichomes per microscopic view by almost 7 folds when compared to the black variety. But, improved size of stomata was detected in the black sesame variety by over 1.5 folds compared to the white variety. The germinability analysis had shown that from the sesame white variety, 98 seeds out of the 100 seeds sown were able to germinate, which signifies 98 percent germinability. Whereas 86 seeds out of the 100 seeds sown have germinated in petri dishes from the black sesame variety, which suggests 86 per cent germinability. Therefore, this research obviously showed that the white sesame variety displayed remarkable morphological qualities and, accordingly could be employed for farming purposes.

Keywords: accessions of sesame plant, characterization, growth, morphology

Procedia PDF Downloads 14
3354 Synthesis and Characterization of SiO2/PVA/ SPEEK Composite Membrane for Proton Exchange Membrane Fuel Cell

Authors: M. Yusuf Ansari, Asad Abbas

Abstract:

Proton exchange membrane (PEM) fuel cell is a very efficient and promising energy conversion device. Although Nafion® is considered as benchmark materials for membrane used in PEM fuel cell, it has limitations that restrict its uses. Alternative materials for the membrane is always a challenging field for researchers. Sulfonated poly(ether ether ketone) (SPEEK) is one of the promising material for membrane due to its chemical and mechanical stability and lower cost. In this work, SPEEK is synthesized, and property booster such as silica nanoparticles and polyvinyl alcohol (PVA) are also added to analyse changes in properties such as water uptake, IEC, and conductivity. It has been found that adding PVA support high water uptake and proton conductivity but at large amount of PVA reduces the proton conductivity due to very high water uptake. Adding silica enhances water uptake and proton conductivity.

Keywords: PEM Membrane, sulfonated poly (ether ether ketone) (SPEEK), silica fumes (SiO2), polyvinyl alcohol (PVA)

Procedia PDF Downloads 288
3353 An Evolutionary Perspective on the Role of Extrinsic Noise in Filtering Transcript Variability in Small RNA Regulation in Bacteria

Authors: Rinat Arbel-Goren, Joel Stavans

Abstract:

Cell-to-cell variations in transcript or protein abundance, called noise, may give rise to phenotypic variability between isogenic cells, enhancing the probability of survival under stress conditions. These variations may be introduced by post-transcriptional regulatory processes such as non-coding, small RNAs stoichiometric degradation of target transcripts in bacteria. We study the iron homeostasis network in Escherichia coli, in which the RyhB small RNA regulates the expression of various targets as a model system. Using fluorescence reporter genes to detect protein levels and single-molecule fluorescence in situ hybridization to monitor transcripts levels in individual cells, allows us to compare noise at both transcript and protein levels. The experimental results and computer simulations show that extrinsic noise buffers through a feed-forward loop configuration the increase in variability introduced at the transcript level by iron deprivation, illuminating the important role that extrinsic noise plays during stress. Surprisingly, extrinsic noise also decouples of fluctuations of two different targets, in spite of RyhB being a common upstream factor degrading both. Thus, phenotypic variability increases under stress conditions by the decoupling of target fluctuations in the same cell rather than by increasing the noise of each. We also present preliminary results on the adaptation of cells to prolonged iron deprivation in order to shed light on the evolutionary role of post-transcriptional downregulation by small RNAs.

Keywords: cell-to-cell variability, Escherichia coli, noise, single-molecule fluorescence in situ hybridization (smFISH), transcript

Procedia PDF Downloads 168
3352 The Optimization of Immobilization Conditions for Biohydrogen Production from Palm Industry Wastewater

Authors: A. W. Zularisam, Sveta Thakur, Lakhveer Singh, Mimi Sakinah Abdul Munaim

Abstract:

Clostridium sp. LS2 was immobilised by entrapment in polyethylene glycol (PEG) gel beads to improve the biohydrogen production rate from palm oil mill effluent (POME). We sought to explore and optimise the hydrogen production capability of the immobilised cells by studying the conditions for cell immobilisation, including PEG concentration, cell loading and curing times, as well as the effects of temperature and K2HPO4 (500–2000 mg/L), NiCl2 (0.1–5.0 mg/L), FeCl2 (100–400 mg/L) MgSO4 (50–200 mg/L) concentrations on hydrogen production rate. The results showed that by optimising the PEG concentration (10% w/v), initial biomass (2.2 g dry weight), curing time (80 min) and temperature (37 °C), as well as the concentrations of K2HPO4 (2000 mg/L), NiCl2 (1 mg/L), FeCl2 (300 mg/L) and MgSO4 (100 mg/L), a maximum hydrogen production rate of 7.3 L/L-POME/day and a yield of 0.31 L H2/g chemical oxygen demand were obtained during continuous operation. We believe that this process may be potentially expanded for sustained and large-scale hydrogen production.

Keywords: hydrogen, polyethylene glycol, immobilised cell, fermentation, palm oil mill effluent

Procedia PDF Downloads 273
3351 Role of Autophagic Lysosome Reformation for Cell Viability in an in vitro Infection Model

Authors: Muhammad Awais Afzal, Lorena Tuchscherr De Hauschopp, Christian Hübner

Abstract:

Introduction: Autophagy is an evolutionarily conserved lysosome-dependent degradation pathway, which can be induced by extrinsic and intrinsic stressors in living systems to adapt to fluctuating environmental conditions. In the context of inflammatory stress, autophagy contributes to the elimination of invading pathogens, the regulation of innate and adaptive immune mechanisms, and regulation of inflammasome activity as well as tissue damage repair. Lysosomes can be recycled from autolysosomes by the process of autophagic lysosome reformation (ALR), which depends on the presence of several proteins including Spatacsin. Thus ALR contributes to the replenishment of lysosomes that are available for fusion with autophagosomes in situations of increased autophagic turnover, e.g., during bacterial infections, inflammatory stress or sepsis. Objectives: We aimed to assess whether ALR plays a role for cell survival in an in-vitro bacterial infection model. Methods: Mouse embryonic fibroblasts (MEFs) were isolated from wild-type mice and Spatacsin (Spg11-/-) knockout mice. Wild-type MEFs and Spg11-/- MEFs were infected with Staphylococcus aureus (multiplication of infection (MOI) used was 10). After 8 and 16 hours of infection, cell viability was assessed on BD flow cytometer through propidium iodide intake. Bacterial intake by cells was also calculated by plating cell lysates on blood agar plates. Results: in-vitro infection of MEFs with Staphylococcus aureus showed a marked decrease of cell viability in ALR deficient Spatacsin knockout (Spg11-/-) MEFs after 16 hours of infection as compared to wild-type MEFs (n=3 independent experiments; p < 0.0001) although no difference was observed for bacterial intake by both genotypes. Conclusion: Suggesting that ALR is important for the defense of invading pathogens e.g. S. aureus, we observed a marked increase of cell death in an in-vitro infection model in cells with compromised ALR.

Keywords: autophagy, autophagic lysosome reformation, bacterial infections, Staphylococcus aureus

Procedia PDF Downloads 147
3350 In vitro Comparison Study of Biologically Synthesized Cupper-Disulfiram Nanoparticles with Its Free Corresponding Complex as Therapeutic Approach for Breast and Liver Cancer

Authors: Marwa M. Abu-Serie, Marwa M. Eltarahony

Abstract:

The search for reliable, effective, and safe nanoparticles (NPs) as a treatment for cancer is a pressing priority. In this study, Cu-NPs were fabricated by Streptomyces cyaneofuscatus through simultaneous bioreduction strategy of copper nitrate salt. The as-prepared Cu-NPs subjected to structural analysis; energy-dispersive X-ray spectroscopy, elemental mapping, X-ray diffraction, transmission electron microscopy, and ζ-potential. These biological synthesized Cu-NPs were mixed with disulfiram (DS), forming a nanocomplex of Cu-DS with a size of ~135 nm. The prepared nanocomplex (nanoCu-DS) exhibited higher anticancer activity than that of free complex of DS-Cu, Cu-NPs, and DS alone. This was illustrated by the lowest IC50 of nanoCu-DS (< 4 µM) against human breast and liver cancer cell lines comparing with DS-Cu, Cu-NPs, and DS (~8, 22.98-33.51 and 11.95-14.86, respectively). Moreover, flow cytometric analysis confirmed that higher apoptosis percentage range of nanoCu-DS-treated in MDA-MB 231, MCF-7, Huh-7, and HepG-2 cells (51.24-65.28%) than free complex of Cu-DS ( < 4.5%). Regarding inhibition potency of liver and breast cancer cell migration, no significant difference was recorded between free and nanocomplex. Furthermore, nanoCu-DS suppressed gene expression of β-catenine, Akt, and NF-κB and upregulated p53 expression (> 3, >15, > 5 and ≥ 3 folds, respectively) more efficiently than free complex (all ~ 1 fold) in MDA-MB 231 and Huh-7 cells. Our finding proved this prepared nano complex has a powerful anticancer activity relative to free complex, thereby offering a promising cancer treatment.

Keywords: biologically prepared Cu-NPs, breast cancer cell lines, liver cancer cell lines, nanoCu- disulfiram

Procedia PDF Downloads 191
3349 Mentha crispa Essential Oil and Rotundifolone Analogues: Cytotoxic Effect on Glioblastoma

Authors: Damião Sousa, Hasan Turkez, Ozlem Tozlu, Tamires Lima

Abstract:

Glioblastoma (GBM) is an aggressive cancer from the brain and with high prevalence and significant morbimortality. Therefore, it is necessary to investigate new therapeutic options against this pathology. Thus, the purpose of this study was to evaluate the antitumor activity from Mentha crispa essential oil (MCEO), its major constituent rotundifolone (ROT) and a series of six analogues on human U87MG glioblastoma cell line. The antitumor effects of the compounds on human U87MG-GBM cell line were assessed using in vitro cell viability assays. In addition, biosafety tests were performed on cultured human blood cells. The data show that MCEO, 1,2-perillaldehyde epoxide (EPER1) and perillaldehyde (PALD) were the most cytotoxic compounds against the U87MG cells, with IC50 values of 16.263, 15.087 and 14.888 μg/mL, respectively. The treatment with MCEO, EPER1 and PALD did not lead to damage in blood cells. These chemical analogues may be useful as prototypes for development of novel antitumor drugs due to their promising activities and toxicological safety.

Keywords: antitumor activity, cancer, natural products, terpenes

Procedia PDF Downloads 153
3348 Regulation of Apoptosis in Human Lung Cancer NCI-H226 Cells through Caspase – Dependent Mechanism by Benjakul Extract

Authors: Pintusorn Hansakul, Ruchilak Rattarom, Arunporn Itharat

Abstract:

Background: Benjakul, a Thai traditional herbal formulation, comprises of five plants: Piper chaba, Piper sarmentosum, Piper interruptum, Plumbago indica, and Zingiber officinale. It has been widely used to treat cancer patients in the context of folk medicine in Thailand. This study aimed to investigate the cytotoxic effect of the ethanol extract of Benjakul against three non-small cell lung cancer (NSCLC) cell lines (NCI-H226, A549, COR-L23), small cell lung cancer (SCLC) cell line NCI-H1688 and normal lung fibroblast cell line MRC-5. The study further examined the molecular mechanisms underlying its cytotoxicity via induction of apoptosis in NCI-H226 cells. Methods: The cytotoxic effect of Benjakul was determined by SRB assay. The effect of Benjakul on cell cycle distribution was assessed by flow cytometric analysis. The apoptotic effects of Benjakul were determined by sub-G1 quantitation and Annexin V-FITC/PI flow cytometric analyses as well as by changes in caspase-3 activity. Results: Benjakul exerted potent cytotoxicity on NCI-H226 and A549 cells but lower cytotoxicity on COR-L23 and NCI-H1688 cells without any cytotoxic effect on normal cells. Molecular studies showed that Benjakul extract induced G2/M phase arrest in human NCI-H226 cells in a dose-dependent manner. The highest concentration of Benjakul (150 μg/ml) led to the highest increase in the G2/M population at 12 h, followed by the highest increase in the sub-G1 population (apoptotic cells) at 60 h. Benjakul extract also induced early apoptosis (AnnexinV +/PI−) in NCI-H226 cells in a dose- and time- dependent manner. Moreover, treatment with 150 μg/ml Benjakul extract for 36 h markedly increased caspase-3 activity by 3.5-fold, and pretreatment with the general caspase inhibitor z-VAD-fmk completely abolished such activity. Conclusions: This study reveals for the first time the regulation of apoptosis in human lung cancer NCI-H226 cells through caspase-dependent mechanism by Benjakul extract.

Keywords: apoptosis, Benjakul, caspase activation, cytotoxicity

Procedia PDF Downloads 446
3347 Automated Computer-Vision Analysis Pipeline of Calcium Imaging Neuronal Network Activity Data

Authors: David Oluigbo, Erik Hemberg, Nathan Shwatal, Wenqi Ding, Yin Yuan, Susanna Mierau

Abstract:

Introduction: Calcium imaging is an established technique in neuroscience research for detecting activity in neural networks. Bursts of action potentials in neurons lead to transient increases in intracellular calcium visualized with fluorescent indicators. Manual identification of cell bodies and their contours by experts typically takes 10-20 minutes per calcium imaging recording. Our aim, therefore, was to design an automated pipeline to facilitate and optimize calcium imaging data analysis. Our pipeline aims to accelerate cell body and contour identification and production of graphical representations reflecting changes in neuronal calcium-based fluorescence. Methods: We created a Python-based pipeline that uses OpenCV (a computer vision Python package) to accurately (1) detect neuron contours, (2) extract the mean fluorescence within the contour, and (3) identify transient changes in the fluorescence due to neuronal activity. The pipeline consisted of 3 Python scripts that could both be easily accessed through a Python Jupyter notebook. In total, we tested this pipeline on ten separate calcium imaging datasets from murine dissociate cortical cultures. We next compared our automated pipeline outputs with the outputs of manually labeled data for neuronal cell location and corresponding fluorescent times series generated by an expert neuroscientist. Results: Our results show that our automated pipeline efficiently pinpoints neuronal cell body location and neuronal contours and provides a graphical representation of neural network metrics accurately reflecting changes in neuronal calcium-based fluorescence. The pipeline detected the shape, area, and location of most neuronal cell body contours by using binary thresholding and grayscale image conversion to allow computer vision to better distinguish between cells and non-cells. Its results were also comparable to manually analyzed results but with significantly reduced result acquisition times of 2-5 minutes per recording versus 10-20 minutes per recording. Based on these findings, our next step is to precisely measure the specificity and sensitivity of the automated pipeline’s cell body and contour detection to extract more robust neural network metrics and dynamics. Conclusion: Our Python-based pipeline performed automated computer vision-based analysis of calcium image recordings from neuronal cell bodies in neuronal cell cultures. Our new goal is to improve cell body and contour detection to produce more robust, accurate neural network metrics and dynamic graphs.

Keywords: calcium imaging, computer vision, neural activity, neural networks

Procedia PDF Downloads 87
3346 Cotton Transplantation as a Practice to Escape Infection with Some Soil-Borne Pathogens

Authors: E. M. H. Maggie, M. N. A. Nazmey, M. A. Abdel-Sattar, S. A. Saied

Abstract:

A successful trial of transplanting cotton is reported. Seeds grown in trays for 4-5 weeks in an easily prepared supporting medium such as peat moss or similar plant waste are tried. Careful transplanting of seedlings, with root system as intact as possible, is being made in the permanent field. The practice reduced damping-off incidence rate and allowed full winter crop revenues. Further work is needed to evaluate certain parameters such as growth curve, flowering curve, and yield at economic bases.

Keywords: cotton, transplanting cotton, damping-off diseases, environment sciences

Procedia PDF Downloads 370
3345 In vitro Antioxidant and Antisickling Effects of Aerva javanica, and Ficus palmata Extracts on Sickle Cell Anemia

Authors: E. A. Alaswad, H. M. Choudhry, F. Z. Filimban

Abstract:

Sickle Cell Anemia (SCA) is one type of blood diseases related to autosomal disorder. The sickle shaped red blood cells are the main cause of many problems in the blood vessels and capillaries. Aerva Javanica (J) and Ficus Palmata (P) are medicinal plants that have many popular uses and have been proved their efficacy. The aim of this study was to assess the antioxidants activity and the antisickling effect of J and P extractions. The period of this study, air-dried leaves of J, and P plants were ground and the active components were extracted by maceration in water (W) and methanol (M) as solvents. The antioxidants activity of JW, PW, JM, and PM were assessed by way of the radical scavenging method using 2,2-diphenyl-1-picrylhydrazyl (DPPH). To determine the antisickling effect of J and P extracts. 20 samples were collected from sickle cell anemia patients. Different concentrations of J and P extracts (200 and 110 μg/mL) were added on the sample and incubated. A drop of each sample was examined with light microscope. Normal and sickled RBCs were calculated and expressed as the percent of sickling. The stabilization effect of the extracts was measured by the osmotic fragility test for erythrocytes. The finding suggests as estimated by DPPH method, all the extracts showed an antioxidant activity with a significant inhibition of the DPPH radicals. PM has the least IC50% with 71.49 μg/ml while JM was the most with 408.49 μg/ml. Sickle cells treated with extracts at different concentrations significantly reduced the percentage of sickling compering to control samples. However, JM 200 μg/mL give the highest anti-sickling affect with 17.4% of sickling compared to control 67.5 of sickling while PM at 200 μg/mL showed the highest membrane cell stability. In a conclusion, the results showed that J and P extracts have antisickling effects. Therefore, the Aerva javanica and Ficus palmata may have a role in SCA management and a good impact on the patient's lives.

Keywords: Aerva javanica, antioxidant, antisickling, Ficus palmata, sickle cell anemia

Procedia PDF Downloads 176
3344 Mobile Traffic Management in Congested Cells using Fuzzy Logic

Authors: A. A. Balkhi, G. M. Mir, Javid A. Sheikh

Abstract:

To cater the demands of increasing traffic with new applications the cellular mobile networks face new changes in deployment in infrastructure for making cellular networks heterogeneous. To reduce overhead processing the densely deployed cells require smart behavior with self-organizing capabilities with high adaptation to the neighborhood. We propose self-organization of unused resources usually excessive unused channels of neighbouring cells with densely populated cells to reduce handover failure rates. The neighboring cells share unused channels after fulfilling some conditional candidature criterion using threshold values so that they are not suffered themselves for starvation of channels in case of any abrupt change in traffic pattern. The cells are classified as ‘red’, ‘yellow’, or ‘green’, as per the available channels in cell which is governed by traffic pattern and thresholds. To combat the deficiency of channels in red cell, migration of unused channels from under-loaded cells, hierarchically from the qualified candidate neighboring cells is explored. The resources are returned back when the congested cell is capable of self-contained traffic management. In either of the cases conditional sharing of resources is executed for enhanced traffic management so that User Equipment (UE) is provided uninterrupted services with high Quality of Service (QoS). The fuzzy logic-based simulation results show that the proposed algorithm is efficiently in coincidence with improved successful handoffs.

Keywords: candidate cell, channel sharing, fuzzy logic, handover, small cells

Procedia PDF Downloads 123
3343 NS5ABP37 Inhibits Liver Cancer by Impeding Lipogenesis and Cholesterogenesis

Authors: Shenghu Feng, Jun Cheng

Abstract:

The molecular mechanism underlying nonalcoholic fatty liver disease (NAFLD) progression to hepatocellular carcinoma (HCC) remains unknown. In this study, immunohistochemistry staining result showed that NS5ABP37 protein expression decreased as with increasing degree of HCC malignancy. In agreement, NS5ABP37 protein overexpression significantly suppressed cell proliferation, caused G1/S cell cycle arrest, and induced apoptosis by increasing caspase-3/7 activity and cleaved caspase-3 levels. In addition, NS5ABP37 overexpression resulted in decreased intracellular TG and TC contents, with level reduction in SREBPs and downstream effectors. Furthermore, NS5ABP37 overexpression decreased SREBP1c and SREBP2 levels by inducing their respective promoters. Finally, ROS levels and ER-stress were both induced by NS5ABP37 overexpression. These findings together demonstrate that NS5ABP37 inhibits cancer cell proliferation and promotes apoptosis, by altering SREBP-dependent lipogenesis and cholesterogenesis in HepG2 cells and inducing oxidative stress and ER stress.

Keywords: NS5ABP37, liver cancer, lipid metabolism, oxidative stress, ER stress

Procedia PDF Downloads 155
3342 Quercetin and INT3 Inhibits Endocrine Therapy Resistance and Epithelial to Mesenchymal Transition in MCF7 Breast Cancer Cells

Authors: S. Pradhan, D. Pradhan, G. Tripathy

Abstract:

Anti-estrogen treatment resistant is a noteworthy reason for disease relapse and mortality in estrogen receptor alpha (ERα)- positive breast cancers. Tamoxifen or estrogen withdrawal increases the dependance of breast malignancy cells on INT3 signaling. Here, we researched the contribution of Quercetin and INT3 signaling in endocrine resistant breast cancer cells. Methods: We utilized two models of endocrine therapies resistant (ETR-) breast cancer: tamoxifen-resistant (TamR) and long term estrogen-deprived (LTED) MCF7 cells. We assessed the migratory and invasive limit of these cells by Transwell assay. Expression of epithelial to mesenchymal transition (EMT) controllers and in addition INT3 receptors and targets were assessed by real-time PCR and western blot analysis. Besides, we tried in vitro anti-Quercetin monoclonal antibodies (mAbs) and gamma secretase inhibitors (GSIs) as potential EMT reversal therapeutic agents. At last, we created stable Quercetin over expessing MCF7 cells and assessed their EMT features and response to tamoxifen. Results:We found that ETR cells acquired an epithelial to mesenchymal transition (EMT) phenotype and showed expanded levels of Quercetin and INT3 targets. Interestingly, we detected higher level of INT3 however lower levels of INT31 and INT32 proposing a switch to targeting through distinctive INT3 receptors after obtaining of resistance. Anti-Quercetin monoclonal antibodies and the GSI PF03084014 were effective in obstructing the Quercetin/INT3 axis and in part inhibiting the EMT process. As a consequence of this, cell migration and invasion were weakened and the stem cell like population was considerably decreased. Genetic hushing of Quercetin and INT3 prompted proportionate impacts. Finally, stable overexpression of Quercetin was adequate to make MCF7 lethargic to tamoxifen by INT3 activation. Conclusions: ETR cells express abnormal amounts of Quercetin and INT3, whose actuation eventually drives invasive conduct. Anti-Quercetin mAbs and GSI PF03084014 lessen expression of EMT molecules decreasing cellular invasiveness. Quercetin overexpression instigates tamoxifen resistance connected to obtaining of EMT phenotype. Our discovering propose that focusing on Quercetin and/or INT3 warrants further clinical assessment as substantial therapeutic methodologies in endocrine-resistant breast cancer.

Keywords: quercetin, INT3, mesenchymal transition, MCF7 breast cancer cells

Procedia PDF Downloads 313
3341 Seamless Mobility in Heterogeneous Mobile Networks

Authors: Mohab Magdy Mostafa Mohamed

Abstract:

The objective of this paper is to introduce a vertical handover (VHO) algorithm between wireless LANs (WLANs) and LTE mobile networks. The proposed algorithm is based on the fuzzy control theory and takes into consideration power level, subscriber velocity, and target cell load instead of only power level in traditional algorithms. Simulation results show that network performance in terms of number of handovers and handover occurrence distance is improved.

Keywords: vertical handover, fuzzy control theory, power level, speed, target cell load

Procedia PDF Downloads 357
3340 Effect of Neem (Aziradicta Indica) Leaf Meal on Growth Performance, Haematology and Serum Biochemistry Indices of Broilers Not Administered Vaccines and Antibiotics

Authors: Ugwuowo Leonard Chidi, Oparaji Chetachukwu Jecinta., Ogidi Chibuzor Agafenachukwu, Onuoha Rebecca Obianuju

Abstract:

This experiment was conducted to investigate the growth performance, haematology and serum biochemistry indices of broiler birds fed diets containing Neem leaf meal. A total of 96 unsexed day-old broiler birds were allocated to four treatments of T1, T2, T3 and T4 and replicated three times with eight birds per replicate in a Completely Randomized Design. The treatments were diets containing 2.0, 4.0, 6.0 and 8.0% Neem leaf meal respectively. Growth performances, packed cell volume, red blood cell count, haemoglobin, white blood cell count, lymphocytes, mean corpuscular volume, mean corpuscular haemoglobin concentration, platelet count, aspartate amino transaminase, alanine amino transaminase, alkaline phosphate, cholesterol, albumin, globulin, urea, glucose, total protein and creatinine were evaluated. Results showed that there were no significant differences (P>0.05) in all the growth performance parameters among the treatments. The results of the experiment showed that there were significant differences (P<0.05) in all the heamatological and serum biochemistry parameters at finisher phases. Mean corpuscular volume, white blood cell count, lymphocytes, red blood cell count, haemoglobin, platelet count, creatinine and triglyceride increased and were highest in treatment two while treatment four had the least values in mean corpuscular volume, urea, white blood cell, haemoglobin and triglyceride. This implies that the levels of inclusion of Neem leaf meal in this experiment did not affect the growth performance of the broiler chicks but the haematological and serum biochemistry indices were affected. Treatment two with a 4% inclusion level of Neem leaf meal has shown the capacity to replace vaccines and antibiotics in broilers due to the positive effects it had on both the haematological and serum biochemistry.

Keywords: leaf meal, broiler, Aziradicta indica, serum biochemistry, haematology

Procedia PDF Downloads 80
3339 A One Dimensional Particle in Cell Model for Excimer Lamps

Authors: W. Benstaali, A. Belasri

Abstract:

In this work we study a planar lamp filled with neon-xenon gas. We use a one-dimensional particle in a cell with Monte Carlo simulation (PIC-MCC) to investigate the effect xenon concentration on the energy deposited on excitation, ionization and ions. A Xe-Ne discharge is studied for a gas pressure of 400 torr. The results show an efficient Xe20-Ne mixture with an applied voltage of 1.2KV; the xenon excitation energy represents 65% form total energy dissipated in the discharge. We have also studied electrical properties and the energy balance a discharge for Xe50-Ne which needs a voltage of 2kv; the xenon energy is than more important.

Keywords: dielectric barrier discharge, efficiency, excitation, lamps

Procedia PDF Downloads 169
3338 Anti-Oxidant and Anti-Cancer Activity of Helix aspersa Aqueous Extract

Authors: Ibtissem El Ouar, Cornelia Braicu, Dalila Naimi, Alexendru Irimie, Ioana Berindan-Neagoe

Abstract:

Helix aspersa, 'the garden snail' is a big land snail widely found in the Mediterranean countries, it is one of the most consumed species in the west of Algeria. It is commonly used in zootherapy to purify blood and to treat cardiovascular diseases and liver problems. The aim of our study is to investigate, the antitumor activity of an aqueous extract from Helix aspersa prepared by the traditional method on Hs578T; a triple negative breast cancer cell line. Firstly, the free radical scavenging activity of H. aspersa extract was assessed by measuring its capability for scavenging the radical 2,2-diphenyl-1-picrylhydrazyl (DPPH), as well as its ability to reduce ferric ion by the FRAP assay (ferric reducing ability). The cytotoxic effect of H. aspersa extract against Hs578T cells was evaluated by the MTT test (3-(4,5- dimethylthiazl-2-yl)-2,5- diphenyltetrazolium bromide)) while the mode of cell death induced by the extract has been determined by fluorescence microscopy using acredine orange/ethidium bromide (AO/EB) probe. The level of TNFα has also measured in cell medium by ELISA method. The results suggest that H. aspersa extract has an antioxidant activity, especially at high concentrations, it can reduce DPPH radical and ferric ion. The MTT test shows that H. aspersa extract has a great cytotoxic effect against breast cancer cells, the IC50 value correspond of the dilution 1% of the crude extract. Moreover, the AO/EB staining shows that TNFα induced necrosis is the main form of cell death induced by the extract. In conclusion, the present study may open new perspectives in the search for new natural anticancer drugs.

Keywords: breast cancer, Helix aspersa, Hs578t cell line, necrosis

Procedia PDF Downloads 426
3337 Microbial Fuel Cells in Waste Water Treatment and Electricity Generation

Authors: Rajalaxmi N., Padma Bhat, Pooja Garag, Pooja N. M., V. S. Hombalimath

Abstract:

Microbial fuel cell (MFC) is the advancement of science that aims at utilizing the oxidizing potential of bacteria for wastewater treatment and production of bio-hydrogen and bio-electricity. Salt-bridge is the economic alternative to highly priced proton-exchange membrane in the construction of a microbial fuel cell. This paper studies the electricity generating capacity of E.coli and Clostridium sporogenes in microbial fuel cells (MFCs). Unlike most of MFC research, this targets the long term goals of renewable energy production and wastewater treatment. In present study the feasibility and potential of bioelectricity production from different wastewater was observed. Different wastewater was primarily treated which were confirmed by the COD tests which showed reduction of COD. We observe that the electricity production of MFCs decreases almost linearly after 120 hrs. The sewage wastewater containing Clostridium sporogenes showed bioelectricity production up to 188mV with COD removal of 60.52%. Sewage wastewater efficiently produces bioelectricity and this also helpful to reduce wastewater pollution load.

Keywords: microbial fuel cell, bioelectricity, wastewater, salt bridge, COD

Procedia PDF Downloads 540
3336 Clonal Evaluation of Malignant Mesothelioma

Authors: Sabahattin Comertpay, Sandra Pastorino, Rosanna Mezzapelle, Mika Tanji, Oriana Strianese, Andrea Napolitano, Tracey Weigel, Joseph Friedberg, Paul Sugarbaker, Thomas Krausz, Ena Wang, Amy Powers, Giovanni Gaudino, Harvey I. Pass, Fatmagul Ozcelik, Barbara L. Parsons, Haining Yang, Michele Carbone

Abstract:

Tumors are thought to be monoclonal in origin. This paradigm arose decades ago, primarily from the study of hematopoietic malignancies and sarcomas. The clonal origin of malignant mesothelioma (MM), a deadly cancer resistant to the current therapies, has not been investigated. Examination of the pleura from patients with MM shows often the presence of multiple pleural nodules, raising the question of whether they represent independent or metastatic growth processes. To investigate the clonality patterns of MM, we used the HUMARA (Human Androgen Receptor) assay to examine 14 sporadic and 2 familial Malignant Mesotheliomas (MM). Of 16 specimens studied, 15 were informative and 14/15 revealed two electrophoretically distinct methylated HUMARA alleles, indicating a polyclonal origin for these tumors. This discovery has important clinical implications, because an accurate assessment of tumor clonality is key to the design of novel molecular strategies for the treatment of MM.

Keywords: malignant mesothelioma, clonal origin, HUMARA, sarcomas

Procedia PDF Downloads 464