Search results for: Cancer metabolism
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 2562

Search results for: Cancer metabolism

2292 Differential Expression of Biomarkers in Cancer Stem Cells and Side Populations in Breast Cancer Cell Lines

Authors: Dipali Dhawan

Abstract:

Cancerous epithelial cells are confined to a primary site by the continued expression of adhesion molecules and the intact basal lamina. However, as the cancer progresses some cells are believed to undergo an epithelial-mesenchymal transition (EMT) event, leading to increased motility, invasion and, ultimately, metastasis of the cells from the primary tumour to secondary sites within the body. These disseminated cancer cells need the ability to self-renew, as stem cells do, in order to establish and maintain a heterogeneous metastatic tumour mass. Identification of the specific subpopulation of cancer stem cells amenable to the process of metastasis is highly desirable. In this study, we have isolated and characterized cancer stem cells from luminal and basal breast cancer cell lines (MDA-MB-231, MDA-MB-453, MDA-MB-468, MCF7 and T47D) on the basis of cell surface markers CD44 and CD24; as well as Side Populations (SP) using Hoechst 33342 dye efflux. The isolated populations were analysed for epithelial and mesenchymal markers like E-cadherin, N-cadherin, Sfrp1 and Vimentin by Western blotting and Immunocytochemistry. MDA-MB-231 cell lines contain a major population of CD44+CD24- cells whereas MCF7, T47D and MDA-MB-231 cell lines show a side population. We observed higher expression of N-cadherin in MCF-7 SP cells as compared to MCF-7NSP (Non-side population) cells suggesting that the SP cells are mesenchymal like cells and hence express increased N-cadherin with stem cell-like properties. There was an expression of Sfrp1 in the MCF7- NSP cells as compared to no expression in MCF7-SP cells, which suggests that the Wnt pathway is expressed in the MCF7-SP cells. The mesenchymal marker Vimentin was expressed only in MDA-MB-231 cells. Hence, understanding the breast cancer heterogeneity would enable a better understanding of the disease progression and therapeutic targeting.

Keywords: cancer stem cells, epithelial to mesenchymal transition, biomarkers, breast cancer

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2291 Coumestrol Induced Apoptosis in Breast Cancer MCF-7 Cells via Redox Cycling of Copper and ROS Generation: Implications of Copper Chelation Strategy in Cancer Treatment

Authors: Atif Zafar Khan, Swarnendra Singh, Imrana Naseem

Abstract:

Breast cancer is one of the most frequent malignancies in women worldwide and a leading cause of cancer-related deaths among women. Therefore, there is a need to identify new chemotherapeutic strategies for cancer treatment. Unlike normal cells, cancer cells contain elevated copper levels which play an integral role in angiogenesis. Copper is an important metal ion associated with the chromatin DNA, particularly with guanine. Thus, targeting copper via copper-specific chelators in cancer cells can serve as effective anticancer strategy. Keeping in view these facts, we evaluated the anticancer activity and copper-dependent cytotoxic effect of coumestrol (phytoestrogen in soybean products) in breast cancer MCF-7 cells. Coumestrol inhibited proliferation and induced apoptosis in MCF-7 cells, which was prevented by copper chelator neocuproine and ROS scavengers. Coumestrol treatment induced ROS generation coupled to DNA fragmentation, up-regulation of p53/p21, cell cycle arrest at G1/S phase, mitochondrial membrane depolarization and caspases 9/3 activation. All these effects were suppressed by ROS scavengers and neocuproine. These results suggest that coumestrol targets elevated copper for redox cycling to generate ROS leading to DNA fragmentation. DNA damage leads to p53 up-regulation which directs the cell cycle arrest at G1/S phase and promotes caspase-dependent apoptosis of MCF-7 cells. In conclusion, coumestrol induces pro-oxidant cell death by chelating cellular copper to produce copper-coumestrol complexes that engages in redox cycling in breast cancer cells. Thus, targeting elevated copper levels might be a potential therapeutic strategy for selective cytotoxic action against malignant cells.

Keywords: apoptosis, breast cancer, copper chelation, coumestrol, reactive oxygens species, redox cycling

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2290 MITOS-RCNN: Mitotic Figure Detection in Breast Cancer Histopathology Images Using Region Based Convolutional Neural Networks

Authors: Siddhant Rao

Abstract:

Studies estimate that there will be 266,120 new cases of invasive breast cancer and 40,920 breast cancer induced deaths in the year of 2018 alone. Despite the pervasiveness of this affliction, the current process to obtain an accurate breast cancer prognosis is tedious and time consuming. It usually requires a trained pathologist to manually examine histopathological images and identify the features that characterize various cancer severity levels. We propose MITOS-RCNN: a region based convolutional neural network (RCNN) geared for small object detection to accurately grade one of the three factors that characterize tumor belligerence described by the Nottingham Grading System: mitotic count. Other computational approaches to mitotic figure counting and detection do not demonstrate ample recall or precision to be clinically viable. Our models outperformed all previous participants in the ICPR 2012 challenge, the AMIDA 2013 challenge and the MITOS-ATYPIA-14 challenge along with recently published works. Our model achieved an F- measure score of 0.955, a 6.11% improvement in accuracy from the most accurate of the previously proposed models.

Keywords: breast cancer, mitotic count, machine learning, convolutional neural networks

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2289 A Molecular Modelling Approach for Identification of Lead Compound from Rhizomes of Glycosmis Pentaphylla for Skin Cancer Treatment

Authors: Rahul Shrivastava, Manish Tripathi, Mohmmad Yasir, Shailesh Singh

Abstract:

Life style changes and depletion in atmospheric ozone layer in recent decades lead to increase in skin cancer including both melanoma and nonmelanomas. Natural products which were obtained from different plant species have the potential of anti skin cancer activity. In regard of this, present study focuses the potential effect of Glycosmis pentaphylla against anti skin cancer activity. Different Phytochemical constituents which were present in the roots of Glycosmis pentaphylla were identified and were used as ligands after sketching of their structures with the help of ACD/Chemsketch. These ligands are screened for their anticancer potential with proteins which are involved in skin cancer effects with the help of pyrx software. After performing docking studies, results reveal that Noracronycine secondary metabolite of Glycosmis pentaphylla shows strong affinity of their binding energy with Ribosomal S6 Kinase 2 (2QR8) protein. Ribosomal S6 Kinase 2 (2QR8) has an important role in the cell proliferation and transformation mediated through by N-terminal kinase domain and was induced by the tumour promoters such as epidermal growth factor. It also plays a key role in the neoplastic transformation of human skin cells and in skin cancer growth. Noracronycine interact with THR-493 and MET-496 residue of Ribosomal S6 Kinase 2 protein with binding energy ΔG = -8.68 kcal/mole. Thus on the basis of this study we can say that Noracronycine which present in roots of Glycosmis pentaphylla can be used as lead compound against skin cancer.

Keywords: glycosmis pentaphylla, pyrx, ribosomal s6 kinase, skin cancer

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2288 Identification of Target Receptor Compound 10,11-Dihidroerisodin as an Anti-Cancer Candidate

Authors: Srie Rezeki Nur Endah, Richa Mardianingrum

Abstract:

Cancer is one of the most feared diseases and is considered the leading cause of death worldwide. Generally, cancer drugs are synthetic drugs with relatively more expensive prices and have harmful side effects, so many people turn to traditional medicine, for example by utilizing herbal medicine. Erythrina poeppigiana is one of the plants that can be used as a medicinal plant containing 10,11-dihidroerisodin compounds that are useful anticancer etnofarmakologi. The purpose of this study was to identify the target of 10,11 dihydroerisodin receptor compound as in silico anticancer candidate. The pure isolate was tested physicochemically by MS (Mass Spectrometry), UV-Vis (Ultraviolet – Visible), IR (Infra Red), 13C-NMR (Carbon-13 Nuclear Magnetic Resonance), 1H-NMR (Hydrogen-1 Nuclear Magnetic Resonance), to obtain the structure of 10,11-dihydroerisodin alkaloid compound then identified to target receptors in silico. From the results of the study, it was found that 10,11-dihydroerisodin compound can work on the Serine / threonine-protein kinase Chk1 receptor that serves as an anti-cancer candidate.

Keywords: anti-cancer, Erythrina poeppigiana, target receptor, 10, 11- dihidroerisodin

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2287 In vitro and vivo Studies for Assessing the Anti-Proliferative, Anti-Migration and Apoptotic Activity of A. squamosa L. Leaves Extract

Authors: Rawan Al-Nemari, Abdulrahman Al-Senaidy, Abdelhabib Semlali

Abstract:

Background and objectives: The most common cause of death in women worldwide is breast cancer. Regarding all chemotherapy disadvantages and side effects, it’s becoming necessary to identify natural products that target cancer cells with lesser harmful side effects on non-targeted cells and biological environment. Different parts of A. squamosa L., commonly known as custard apple, show varied therapeutic effects. The objective of this study is to investigate in vitro and in vivo, the anti-cancer activity of A. squamosa leaves extract. Methods: The physiological responses using MTT, nucleus staining, and LDH assays were used to evaluate cell survival and proliferation in both ER+ and ER- cells when they were exposed to extract. Monolayer wound repair assay was used to investigate the effect of extracts on cell migration. Apoptotic gene’s expression was investigated by real-time polymerase chain reaction. To study the effect of the extract on the size of tumor, breast cancer induced rats were used. Results: A. squamosa leaves extract showed high anti-proliferative and cytotoxicity effects against different breast cancer cell lines with high concentration, 100 ug/ml. The extracts have reduced the cells wound closure. Polymerase chain reaction revealed downregulation of Bcl-2 and upregulation of Bax. In breast cancer model animal developed in our laboratory, after 4 weeks treatment, treated groups have shown smaller tumor size in comparison with control group (n=4). Conclusion: These results suggest that A. squamosa leaves extract has anti-cancer activity against breast cancer in both in vitro and in vivo, and it may be developed as a potential novel agent to treat breast cancer.

Keywords: apoptosis, breast cancer, migration, proliferation

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2286 VHL, PBRM1, and SETD2 Genes in Kidney Cancer: A Molecular Investigation

Authors: Rozhgar A. Khailany, Mehri Igci, Emine Bayraktar, Sakip Erturhan, Metin Karakok, Ahmet Arslan

Abstract:

Kidney cancer is the most lethal urological cancer accounting for 3% of adult malignancies. VHL, a tumor-suppressor gene, is best known to be associated with renal cell carcinoma (RCC). The VHL functions as negative regulator of hypoxia inducible factors. Recent sequencing efforts have identified several novel frequent mutations of histone modifying and chromatin remodeling genes in ccRCC (clear cell RCC) including PBRM1 and SETD2. The PBRM1 gene encodes the BAF180 protein, which involved in transcriptional activation and repression of selected genes. SETD2 encodes a histone methyltransferase, which may play a role in suppressing tumor development. In this study, RNAs of 30 paired tumor and normal samples that were grouped according to the types of kidney cancer and clinical characteristics of patients, including gender and average age were examined by RT-PCR, SSCP and sequencing techniques. VHL, PBRM1 and SETD2 expressions were relatively down-regulated. However, statistically no significance was found (Wilcoxon signed rank test, p > 0.05). Interestingly, no mutation was observed on the contrary of previous studies. Understanding the molecular mechanisms involved in the pathogenesis of RCC has aided the development of molecular-targeted drugs for kidney cancer. Further analysis is required to identify the responsible genes rather than VHL, PBRM1 and SETD2 in kidney cancer.

Keywords: kidney cancer, molecular biomarker, expression analysis, mutation screening

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2285 Knowledge And Attitude of Female Workers in Selected Rural Local Government Areas of Imo State, Nigeria Towards Cervical Cancer and Its Screening

Authors: Peter O. Nwadike, Sylvia O. Anyadoh-Nwadike, Chukwunonyerem Ogwunga, I. N. S. Dozie

Abstract:

Purpose: This study was aimed at determining the knowledge and attitude of female workers in six selected rural Local Government Areas of Imo State (Ezinihitte Mbaise, Ngor Okpala, Ohaji/Egbema, Ideato South, Ihitte Uboma and Obowo) towards cervical cancer and its screening. Methodology: Data was collected using a validated open-ended, semi-structured questionnaire. After responses to the questionnaire were received, a seminar on Cervical cancer and its screening was delivered to the respondents. Afterward, a second set of the same questionnaires was administered to the same respondents. A total of 460 women of reproductive age were randomly selected upon their informed consent. Data obtained/responses were analyzed using simple percentages. The chi-square test was used to assess the relationship by testing the hypothesis. Result: Results revealed that, before the seminar, a high average percentage of 72.2% (332) of respondents had not heard of cervical cancer while 27.8% (128) had heard. Of those who know about Cervical cancer, an average of 70.3% (90) showed low knowledge. The majority of respondents, 366 (79.6%), had poor attitudes toward screening. They mostly implicated lack of awareness 205 (44.6%) and lack of funds 104 (22.6%) as major reasons for not participating in the screening test. Few 128 (27.8%) agreed to go for screening and vaccination. After the awareness, 400 (87%) agreed to go for the screening test and vaccination if free/affordable. None of the participants had ever been screened. A significant relationship between attitude to cervical cancer and level of knowledge and academic level and attitude to cervical cancer screening was obtained. Conclusion: This calls for continued enlightenment about cervical cancer screening, especially as soon as sexual activity begins.

Keywords: cervical cancer, rural areas, Imo state, knowledge, attitude

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2284 Temporal Trends in the Urban Metabolism of Riyadh, Saudi Arabia

Authors: Naif Albelwi, Alan Kwan, Yacine Rezgui

Abstract:

Cities with rapid growth face tremendous challenges not only to provide services to meet this growth but also to assure that this growth occurs in a sustainable way. The consumption of material, energy, and water resources is inextricably linked to population growth with a unique impact in urban areas, especially in light of significant investments in infrastructure to support urban development. Urban Metabolism (UM) is becoming popular as it provides a framework accounting the mass and energy flows through a city. The objective of this study is to determine the energy and material flows of Riyadh, Saudi Arabia using locally generated data from 1996 and 2012 and analyzing the temporal trends of energy and material flows. Preliminary results show that while the population of Riyadh grew 90% since 1996, the input and output flows have increased at higher rate. Results also show increasing in energy mobile consumption from 61k TJ in 1996 to 157k TJ in 2012 which points to Riyadh’s inefficient urban form. The study findings highlight the importance to develop effective policies for improving the use of resources.

Keywords: energy and water consumption, sustainability, urban development, urban metabolism

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2283 Microvesicles in Peripheral and Uterine Blood in Women with Atypical Hyperplasia and Endometrioid Endometrial Cancer

Authors: Barbara Zapala, Marek Dziechciowski, Olaf Chmura, Monika Piwowar, Katarzyna Gawlik, Dorota Pawlicka-Gosiewska, Krzysztof Skotniczny, Bogdan Solnica, Kazimierz Pitynski

Abstract:

BACKGROUND: Endometrial cancer is one of the most common gynecologic malignancy in developed countries.We hypothesized that amount of circulating micro-particles in blood may be connected with the development of endometrial hyperplasia and endometrial cancer. The aim of this study was to measure the micro-particles amount in uterine venous blood and in peripheral venous blood in women with atypical endometrial hyperplasia and endometrioid endometrial cancer. MATERIALS AND METHODS: By using flow cytometry (BD Canto II cytometer) we measured micro-particles amount in citrate plasma samples from peripheral and uterine venous blood of women with atypical hyperplasia of endometrium or endometrial cancer. We determined the amount of total (TF+), endothelial (CD144+) and monocytic (CD14+) micro- particles. RESULTS: Here we show statistically significant higher micro-particle levels in women with atypical hyperplasia of endometrium or endometrial cancer in comparison to healthy women. Performing measurements of the amounts of total, endothelial and monocytic microparticles allow for reliable differentiation between healthy, atypical hyperplasia and endometrial cancer groups. In blood samples from uterine veins the circulating micro-particle levels were significantly different from peripheral blood samples. The micro-particle levels in uterine blood samples were 7-fold higher than in those from peripheral blood of women with both atypical hyperplasia of endometrium and endometrial cancer when compared to the control group of healthy women. CONCLUSION: These results strongly suggested that the level of circulating micro-particles may be a sign of endometrial cancer development, however the detailed study is needed focusing on molecular processes passed through this small circulating molecules.

Keywords: endometrial cancer, endometrial hyperplasia, microvesicles, uterine blood

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2282 Six Tropical Medicinal Plants Effects in the Treatment of Prostate Diseases in Forty Different Patients

Authors: T. Nalowa, L. Foncha, S. Eposi

Abstract:

Prostate enlargement, prostate cancer are major global health problems affecting many men as they advance in age. It is highly recommended to encourage older men to get Prostate Specific Antigen test screening frequently. Conventional treatments like radiation, chemotherapy are associated with many side effects. And this situation is a call for concern. Traditional medicine is affordable, easily prepared with little or no side effects and it contains many phytochemicals. The study aims to find the cure for prostate cancer and prostate enlargement by extracting products from plant tissues of specific herbs to determine anti-inflammatory, anti-cancer, and anti-hematuria properties. Descriptive statistical analysis was applied to describe the data process. The commonly used method of preparation was extraction. Overall, 40 patients were classified based on their medical conditions on their underlying user report. Rural communities in Fako are rich sources of plants with medicinal properties. The used plants consequently provide basic information and aid to investigate the cure of prostate cancer and prostate enlargement, with great significance.

Keywords: cancer, enlargement, metastases, prostate

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2281 Hematological Changes in Oral Cancer Patients with Smokable and Chewable Tobacco

Authors: Mohsin Ali Baloch, Saira Baloch

Abstract:

Objective: To analyze hematological changes in patients of oral cancer with history of smokable and chewable tobacco use, and to compare them with healthy controls. Study Design: Descriptive type of study survey. Setting: This study was conducted at the Department of Oral and Maxillofacial Surgery, LUMHS, Jamshoro. Study Period: One year July, 2013 to July, 2014. Subject and Methods: Histopathologically confirmed hundred cases of oral cancer with the history of smokable and non-smokable tobacco were selected to analyze the hematological variation. Inclusion Criteria: Histopathologically diagnosed patients of oral squamous cell carcinoma, with history of smokable and non-smokable tobacco. Exclusion Criteria: Patient with any systemic medically compromising problem, terminally ill patients, radio or chemotherapeutically treated patients, patients with metastasis to lungs or any distant metastasis, patients with the history of more than one well-defined etiological factor involved. Results: There were 73% patients of oral cancer reported with anemic. Significantly lower values of Hb, platelet, and higher mean values of ESR, TLC, and were observed in both groups of oral cancer patients; tobacco smokers and tobacco chewers as compared to non-smokers healthy controls. There was more decline in the level of haemoglobin and incline in the level of ESR observed in tobacco chewer oral cancer patients as compared to tobacco smokers patients, while TLC was more observed in smokers. Conclusion: Oral cancer patients with a history of chewable/smokable tobacco have likely worse hematological profile, which increases the anesthetic and surgical challenges for maxillofacial surgeons, which have a significant impact on treatment planning as well.

Keywords: oral cancer, hematological variations, tobacco, smokers

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2280 Fluorescence Gold Nanoparticles: Sensing Properties and Cytotoxicity Studies in MCF-7 Human Breast Cancer Cells

Authors: Cristina Núñez, Rufina Bastida, Elena Labisbal, Alejandro Macías, María T. Pereira, José M. Vila

Abstract:

A highly selective quinoline-based fluorescent sensor L was designed in order to functionalize gold nanoparticles (GNPs@L). The cytotoxicity of compound L and GNPs@L on the MCF-7 breast cancer cells was explored and it was observed that L and GNPs@L compounds induced apoptosis in MCF-7 cancer cells. The cellular uptake of the hybrid system GNPs@L was studied using confocal laser scanning microscopy (CLSM).

Keywords: cytotoxicity, fluorescent probes, nanoparticles, quinoline

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2279 Determination of Myocardial Function Using Heart Accumulated Radiopharmaceuticals

Authors: C. C .D. Kulathilake, M. Jayatilake, T. Takahashi

Abstract:

The myocardium is composed of specialized muscle which relies mainly on fatty acid and sugar metabolism and it is widely contribute to the heart functioning. The changes of the cardiac energy-producing system during heart failure have been proved using autoradiography techniques. This study focused on evaluating sugar and fatty acid metabolism in myocardium as cardiac energy getting system using heart-accumulated radiopharmaceuticals. Two sets of autoradiographs of heart cross sections of Lewis male rats were analyzed and the time- accumulation curve obtained with use of the MATLAB image processing software to evaluate fatty acid and sugar metabolic functions.

Keywords: autoradiographs, fatty acid, radiopharmaceuticals, sugar

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2278 Quality of Life of Women with Breast Cancer and Its Correlation with Depression and Anxiety

Authors: Maria Malliarou, Efrossini Lyraraki, Pavlos Sarafis, Theodosios Paralikas, Styliani Kotrotsiou, Evangelia Kotrotsiou, Mairy Gouva

Abstract:

Women with breast cancer have to adapt to physical malformations, side effects of chemotherapy, emotional insecurity, and changes in social roles. Inability to recognize the co-morbidity of psychiatric conditions can have an aggravating effect on patient compliance in therapeutic interventions, resulting in treatment delays and an impact on overall survival. The purpose of this study was to identify the quality of life of breast cancer patients undergoing external radiation therapy and to correlate it with depression and anxiety. Patients were asked to respond to an anonymous questionnaire with general demographic and clinical questions, followed by the EORTCQLQ-C30 questionnaire for assessing the quality of life of patients with breast cancer. Hospital Anxiety and Depression Scale (HADS) as well as the Depression, Anxiety and Stress Scale (DASS-21) was also administered. The statistical analysis of the data was done in IBM SPSS. Results indicated that the incidence of anxiety and depression in breast cancer patients is high both in HADS (37.5 % with mild to moderate depression and 62.5 % with significant to severe depression) and DASS - 21 (39.2 % mild to moderate depression and 60.8 % significant to severe) scales. The correlation of anxiety and depression with life quality was negative for HADS (r = -, 810, p = .000) as well as for DASS-21 (r = -, 682, p = .000). The psychological impact of breast cancer on patients is important. Its correlation with the quality of life may lead to better tolerance to treatment and better effectiveness of the therapeutic approach.

Keywords: anxiety, breast cancer, depression, quality of life

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2277 Effects of α-IFN –SingleWalled Carbon NanoTube and α-IFN-PLGA Encapsulated on Breast Cancer in Rats Induced by DMBA by Using CA15-3 Tumor Marker

Authors: Anoosh Eghdami

Abstract:

Background and aim: Conventional anticancer drugs display significant shortcomings which limit their use in cancer therapy. For this reason, important progress has been achieved in the field of nanotechnology to solve these problems and offer a promising and effective alternative for cancer treatment. Tumor markers may also be measured periodically during cancer therapy. Tumor markers may also be measured after treatment has ended to check for recurrence the return of cancer. The aim of this study was to evaluate the effect of nano drug delivery in induced breast cancer with DMBA by using CA15-3 tumor marker. Material and method: the rats were divided into five groups. The first group (control n=15) were fed only sesame oil as a gavage. In the second group n=15,10 mg DMBA was dissolved in 5ml of sesame oil and were fed as a gavage. In addition to DMBA treatment as the second group, in the 3,4and 5 groups after cancer creation, respectively affected by alpha interferon (α-IFN),alpha interferon conjugated with single walled carbon nano tube (α-IFN-SWNT) and encapsulated in poly lactic poly glycolic acid (α-IFN-PLGA). Tumor marker was measured in recent three groups. Results: The ANOVA test was used to determine the differences among the groups. Cancer inducing in rats (group 2) caused a significant increase in blood levels of CA15-3 (P<0.05). Administration of α-IFN, α-IFN –SWNT and α-IFN-PLGA in 3 groups of cancerous rats caused a significant decrease in blood levels of CA15-3 only the group that treated with α-IFN-PLGA (p<0.05). Conclusion: the results of this study indicate that nano drugs more effective than traditional drug in cancer treatment, although further work is needed to elucidate the safety and side effect of these compound in human.

Keywords: breast cancer, nano drug, tumor markers, CA15-3, α-IFN-PLGA, -IFN –SWNT

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2276 Clinical Relevance of TMPRSS2-ERG Fusion Marker for Prostate Cancer

Authors: Shalu Jain, Anju Bansal, Anup Kumar, Sunita Saxena

Abstract:

Objectives: The novel TMPRSS2:ERG gene fusion is a common somatic event in prostate cancer that in some studies is linked with a more aggressive disease phenotype. Thus, this study aims to determine whether clinical variables are associated with the presence of TMPRSS2:ERG-fusion gene transcript in Indian patients of prostate cancer. Methods: We evaluated the clinical variables with presence and absence of TMPRSS2:ERG gene fusion in prostate cancer and BPH association of clinical patients. Patients referred for prostate biopsy because of abnormal DRE or/and elevated sPSA were enrolled for this prospective clinical study. TMPRSS2:ERG mRNA copies in samples were quantified using a Taqman chemistry by real time PCR assay in prostate biopsy samples (N=42). The T2:ERG assay detects the gene fusion mRNA isoform TMPRSS2 exon1 to ERG exon4. Results: Histopathology report has confirmed 25 cases as prostate cancer adenocarcinoma (PCa) and 17 patients as benign prostate hyperplasia (BPH). Out of 25 PCa cases, 16 (64%) were T2: ERG fusion positive. All 17 BPH controls were fusion negative. The T2:ERG fusion transcript was exclusively specific for prostate cancer as no case of BPH was detected having T2:ERG fusion, showing 100% specificity. The positive predictive value of fusion marker for prostate cancer is thus 100% and the negative predictive value is 65.3%. The T2:ERG fusion marker is significantly associated with clinical variables like no. of positive cores in prostate biopsy, Gleason score, serum PSA, perineural invasion, perivascular invasion and periprostatic fat involvement. Conclusions: Prostate cancer is a heterogeneous disease that may be defined by molecular subtypes such as the TMPRSS2:ERG fusion. In the present prospective study, the T2:ERG quantitative assay demonstrated high specificity for predicting biopsy outcome; sensitivity was similar to the prevalence of T2:ERG gene fusions in prostate tumors. These data suggest that further improvement in diagnostic accuracy could be achieved using a nomogram that combines T2:ERG with other markers and risk factors for prostate cancer.

Keywords: prostate cancer, genetic rearrangement, TMPRSS2:ERG fusion, clinical variables

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2275 Shark Cartilage Modulate IL-23/IL-17 Axis by Increasing IFN-γ and Decreasing IL-4 in Patients with Gastric Cancer

Authors: Razieh Zareia, Hassan ZMB, Darush Moslemic, Amrollah Mostafa-Zaded

Abstract:

Introduction: Shark is a murine organism and its cartilage has antitumor peptides to prevent angiogenesis, at least, in vitro. The purpose of our research was to evaluate the immune-effectiveness on imbalance between IL-23/IL-17 axis, as an inflammatory pathway and TGF/Foxp3 T regulatory as a inhibitory pathway of commercial shark cartilage that is available as a non-common dietary supplement in IRAN. Materials and Methods: First investigated an imbalanced supernatant of cytokines exist in patients with gastric cancer by ELISA. Associated with cytokines measuring such as IL-23, IL-17, TGF-β, IL-4, and γ-IFN, then flow cytometry was employed to determine whether the peripheral blood mononuclear cells such as CD4+CD25+Foxp3highT regulatory cells in patients with gastric cancer were changed correspondingly. Results: The simultaneously presented up-regulation IL-17A indicated, at least cytokine level without changing in TGF-β amount or CD4+CD25+Foxp3 T regulatory cells, that there are not a direct correlation between IL-23/IL-17 axis and Treg/TGF-β pathway in patients with gastric cancer treated by shark cartilage, but IL-23 was not expressed differentially in this group. So, accompany these changes, an imbalance between Th1 immunity (γ-IFN production) and TH2 immunity (IL-4 secretion) evaluated in patients with gastric cancer treated by shark cartilage. Conclusion: On the basis of results, we propose that shark cartilage, by reducing IL-4, decreasing IL-17 a central cytokine in angiogenesis and increasing γ-IFN amplify anti-tumor immune responses in patients with gastric cancer.

Keywords: IL-23/IL17 axis, TGF-β/CD4+CD25+Foxp3high T regulatory pathway, γ-IFN, IL-4, shark cartilage, gastric cancer

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2274 Social Appearance Anxiety, Body Dissatisfaction, and Disordered Eating Behavior among Cancer Survivors

Authors: Rose J. Thazhathukunnel, A. G. Smitha

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In the wake of social development, humans overlook the ideal physical appearance, and there is an increasing trend of criticising other’s bodies or offering tips to hide imperfections. Social appearance anxiety demonstrates the association with body dissatisfaction and disordered eating behavior. In this study, we examined the hypothesis that social appearance anxiety, body dissatisfaction, and disordered eating behavior would predict the relation between each among cancer survivors. It was observed that implicit belief to be thin was more pronounced in people with low body dissatisfaction than those with high body dissatisfaction. Results of the study indicated that overall body dissatisfaction and social appearance anxiety were correlated with disordered eating behavior for both men and women cancer survivors of all ages.

Keywords: social appearance anxiety, body dissatisfaction, disordered eating behavior, cancer survivors

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2273 Investigation of FoxM1 Gene Expression in Breast Cancer and Its Relationship with miR-216B-5p Expression Level

Authors: Ramin Mehdiabadi

Abstract:

Background: Breast cancer remains the most prevalent cancer diagnosis and the leading cause of cancer death among women globally, representing 11.7% of new cases and 6.9% of deaths. While the incidence and mortality of major cancers are declining in developed regions like the United States and Western Europe, underdeveloped and developing countries exhibit an increasing trend, attributed to lifestyle factors such as smoking, physical inactivity, and high-calorie diets. Objective: This study explores the intricate relationship between the mammalian transcription factor forkhead box (FoxM1) and the microRNA miR-216b-5p in various subtypes of breast cancer, aiming to deepen the understanding of their roles in tumorigenesis, metastasis, and drug resistance. Methods: Breast cancer subtypes were categorized based on key biomarkers: estrogen receptors, progesterone receptors, and human epidermal growth factor receptor 2. These include luminal A, luminal B, HER2 enriched, triple-negative, and normal-like subtypes. We focused on analyzing the expression levels of FoxM1 and miR-216b-5p, given the known role of FoxM1 in cell proliferation and its implications in cancer pathologies such as lung, gastric, and breast cancers. Concurrently, miR-216b-5p's function as a tumor suppressor was evaluated to ascertain its regulatory effects on FoxM1. Results: Preliminary data indicate a nuanced interplay between FoxM1 and miR-216b-5p, suggesting a potential inverse relationship that varies across breast cancer subtypes. This relationship underscores the dual role of these biomarkers in modulating cancer progression and response to treatments. Conclusion: The findings advocate for the potential of miR-216b-5p to serve as a prognostic biomarker and a therapeutic target, particularly in subtypes where FoxM1 is prominently expressed. Understanding these molecular interactions provides crucial insights into the personalized treatment strategies and could lead to more effective therapeutic interventions in breast cancer management. Implications: The study highlights the importance of molecular profiling in breast cancer treatment and emphasizes the need for targeted therapeutic approaches in managing diverse cancer subtypes, particularly in varying global contexts where lifestyle factors significantly impact cancer dynamics.

Keywords: breast cancer, gene expression, FoxM1, microRNA

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2272 Integrated Social Support through Social Networks to Enhance the Quality of Life of Metastatic Breast Cancer Patients

Authors: B. Thanasansomboon, S. Choemprayong, N. Parinyanitikul, U. Tanlamai

Abstract:

Being diagnosed with metastatic breast cancer, the patients as well as their caretakers are affected physically and mentally. Although the medical systems in Thailand have been attempting to improve the quality and effectiveness of the treatment of the disease in terms of physical illness, the success of the treatment also depends on the quality of mental health. Metastatic breast cancer patients have found that social support is a key factor that helps them through this difficult time. It is recognized that social support in different dimensions, including emotional support, social network support, informational support, instrumental support and appraisal support, are contributing factors that positively affect the quality of life of patients in general, and it is undeniable that social support in various forms is important in promoting the quality of life of metastatic breast patients. However, previous studies have not been dedicated to investigating their quality of life concerning affective, cognitive, and behavioral outcomes. Therefore, this study aims to develop integrated social support through social networks to improve the quality of life of metastatic breast cancer patients in Thailand.

Keywords: social support, metastatic breath cancer, quality of life, social network

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2271 Micro-Ribonucleic Acid-21 as High Potential Prostate Cancer Biomarker

Authors: Regina R. Gunawan, Indwiani Astuti, H. Raden Danarto

Abstract:

Cancer is the leading cause of death worldwide. Cancer is caused by mutations that alter the function of normal human genes and give rise to cancer genes. MicroRNA (miRNA) is a small non-coding RNA that regulates the gen through complementary bond towards mRNA target and cause mRNA degradation. miRNA works by either promoting or suppressing cell proliferation. miRNA level expression in cancer may offer another value of miRNA as a biomarker in cancer diagnostic. miRNA-21 is believed to have a role in carcinogenesis by enhancing proliferation, anti-apoptosis, cell cycle progression and invasion of tumor cells. Hsa-miR-21-5p marker has been identified in Prostate Cancer (PCa) and Benign Prostatic Hyperplasia (BPH) patient’s urine. This research planned to explore the diagnostic performance of miR-21 to differentiate PCa and BPH patients. In this study, urine samples were collected from 20 PCa patients and 20 BPH patients. miR-21 relative expression against the reference gene was analyzed and compared between the two. miRNA expression was analyzed using the comparative quantification method to find the fold change. miR-21 validity in identifying PCa patients was performed by quantifying the sensitivity and specificity with the contingency table. miR-21 relative expression against miR-16 in PCa patient and in BPH patient has 12,98 differences in fold change. From a contingency table of Cq expression of miR-21 in identifying PCa patients from BPH patient, Cq miR-21 has 100% sensitivity and 75% specificity. miR-21 relative expression can be used in discriminating PCa from BPH by using a urine sample. Furthermore, the expression of miR-21 has higher sensitivity compared to PSA (Prostate specific antigen), therefore miR-21 has a high potential to be analyzed and developed more.

Keywords: benign prostate hyperplasia, biomarker, miRNA-21, prostate cancer

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2270 Overview and Pathophysiology of Radiation-Induced Breast Changes as a Consequence of Radiotherapy Toxicity

Authors: Monika Rezacova

Abstract:

Radiation-induced breast changes are a consequence of radiotherapy toxicity over the breast tissues either related to targeted breast cancer treatment or other thoracic malignancies (eg. lung cancer). This study has created an overview of different changes and their pathophysiology. The main conditions included were skin thickening, interstitial oedema, fat necrosis, dystrophic calcifications, skin retractions, glandular atrophy, breast fibrosis and radiation induced breast cancer. This study has performed focused literature search through multiple databases including pubmed, medline and embase. The study has reviewed English as well as non English publications. As a result of the literature the study provides comprehensive overview of radiation-induced breast changes and their pathophysiology with small focus on new development and prevention.

Keywords: radiotherapy toxicity, breast tissue changes, breast cancer treatment, radiation-induced breast changes

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2269 The Role and Importance of Genome Sequencing in Prediction of Cancer Risk

Authors: M. Sadeghi, H. Pezeshk, R. Tusserkani, A. Sharifi Zarchi, A. Malekpour, M. Foroughmand, S. Goliaei, M. Totonchi, N. Ansari–Pour

Abstract:

The role and relative importance of intrinsic and extrinsic factors in the development of complex diseases such as cancer still remains a controversial issue. Determining the amount of variation explained by these factors needs experimental data and statistical models. These models are nevertheless based on the occurrence and accumulation of random mutational events during stem cell division, thus rendering cancer development a stochastic outcome. We demonstrate that not only individual genome sequencing is uninformative in determining cancer risk, but also assigning a unique genome sequence to any given individual (healthy or affected) is not meaningful. Current whole-genome sequencing approaches are therefore unlikely to realize the promise of personalized medicine. In conclusion, since genome sequence differs from cell to cell and changes over time, it seems that determining the risk factor of complex diseases based on genome sequence is somewhat unrealistic, and therefore, the resulting data are likely to be inherently uninformative.

Keywords: cancer risk, extrinsic factors, genome sequencing, intrinsic factors

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2268 The Physiological Effect of Cold Atmospheric Pressure Plasma on Cancer Cells, Cancer Stem Cells, and Adult Stem Cells

Authors: Jeongyeon Park, Yeo Jun Yoon, Jiyoung Seo, In Seok Moon, Hae Jun Lee, Kiwon Song

Abstract:

Cold Atmospheric Pressure Plasma (CAPP) is defined as a partially ionized gas with electrically charged particles at room temperature and atmospheric pressure. CAPP generates reactive oxygen species (ROS) and reactive nitrogen species (RNS), and has potential as a new apoptosis-promoting cancer therapy. With an annular type dielectric barrier discharge (DBD) CAPP-generating device combined with a helium (He) gas feeding system, we showed that CAPP selectively induced apoptosis in various cancer cells while it promoted proliferation of the adipose tissue-derived stem cell (ASC). The apoptotic effect of CAPP was highly selective toward p53-mutated cancer cells. The intracellular ROS was mainly responsible for apoptotic cell death in CAPP-treated cancer cells. CAPP induced apoptosis even in doxorubicin-resistant cancer cell lines, demonstrating the feasibility of CAPP as a potent cancer therapy. With the same device and exposure conditions to cancer cells, CAPP stimulated proliferation of the ASC, a kind of mesenchymal stem cell that is capable of self-renewing and differentiating into adipocytes, chondrocytes, osteoblasts and neurons. CAPP-treated ASCs expressed the stem cell markers and differentiated into adipocytes as untreated ASCs. The increase of proliferation by CAPP in ASCs was offset by a NO scavenger but was not affected by ROS scavengers, suggesting that NO generated by CAPP is responsible for the activated proliferation in ASCs. Usually, cancer stem cells are reported to be resistant to known cancer therapies. When we applied CAPP of the same device and exposure conditions to cancer cells to liver cancer stem cells (CSCs) that express CD133 and epithelial cell adhesion molecule (EpCAM) cancer stem cell markers, apoptotic cell death was not examined. Apoptotic cell death of liver CSCs was induced by the CAPP generated from a device with an air-based flatten type DBD. An exposure of liver CSCs to CAPP decreased the viability of liver CSCs to a great extent, suggesting plasma be used as a promising anti-cancer treatment. To validate whether CAPP can be a promising anti-cancer treatment or an adjuvant modality to eliminate remnant tumor in cancer surgery of vestibular schwannoma, we applied CAPP to mouse schwannoma cell line SC4 Nf2 ‑/‑ and human schwannoma cell line HEI-193. A CAPP treatment leads to anti-proliferative effect in both cell lines. We are currently studying the molecular mechanisms of differential physiological effect of CAPP; the proliferation of ASCs and apoptosis of various cancer cells and CSCs.

Keywords: cold atmospheric pressure plasma, apoptosis, proliferation, cancer cells, adult stem cells

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2267 Recurrence of Papillary Thyroid Cancer with an Interval of 40 Years. Report of an Autopsy Case

Authors: Satoshi Furukawa, Satomu Morita, Katsuji Nishi, Masahito Hitosugi

Abstract:

A 75-year-old woman took thyroidectomy forty years previously. Enlarged masses were seen at autopsy just above and below the left clavicle. We proved the diagnosis of papillary thyroid cancer (PTC) and lung metastasis by histological examinations. The prognosis of PTC is excellent; the 10-year survival rate ranges between 85 and 99%. Lung metastases may be found in 10% of the patients with PTC. We report an unusual case of recurrence of PTC with metastasis to the lung.

Keywords: papillary thyroid cancer, lung metastasis, autopsy, histopathological findings

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2266 Tuberculosis (TB) and Lung Cancer

Authors: Asghar Arif

Abstract:

Lung cancer has been recognized as one of the greatest common cancers, causing the annual mortality rate of about 1.2 million people in the world. Lung cancer is the most prevalent cancer in men and the third-most common cancer among women (after breast and digestive cancers).Recent evidences have shown the inflammatory process as one of the potential factors of cancer. Tuberculosis (TB), pneumonia, and chronic bronchitis are among the most important inflammation-inducing factors in the lungs, among which TB has a more profound role in the emergence of cancer.TB is one of the important mortality factors throughout the world, and 205,000 death cases are reported annually due to this disease. Chronic inflammation and fibrosis due to TB can induce genetic mutation and alternations. Parenchyma tissue of lung is involved in both diseases of TB and lung cancer, and continuous cough in lung cancer, morphological vascular variations, lymphocytosis processes, and generation of immune system mediators such as interleukins, are all among the factors leading to the hypothesis regarding the role of TB in lung cancer Some reports have shown that the induction of necrosis and apoptosis or TB reactivation, especially in patients with immune-deficiency, may result in increasing IL-17 and TNF_α, which will either decrease P53 activity or increase the expression of Bcl-2, decrease Bax-T, and cause the inhibition of caspase-3 expression due to decreasing the expression of mitochondria cytochrome oxidase. It has been also indicated that following the injection of BCG vaccine, the host immune system will be reinforced, and in particular, the rates of gamma interferon, nitric oxide, and interleukin-2 are increased. Therefore, CD4 + lymphocyte function will be improved, and the person will be immune against cancer.Numerous prospective studies have so far been conducted on the role of TB in lung cancer, and it seems that this disease is effective in that particular cancer.One of the main challenges of lung cancer is its correct and timely diagnosis. Unfortunately, clinical symptoms (such as continuous cough, hemoptysis, weight loss, fever, chest pain, dyspnea, and loss of appetite) and radiological images are similar in TB and lung cancer. Therefore, anti-TB drugs are routinely prescribed for the patients in the countries with high prevalence of TB, like Pakistan. Regarding the similarity in clinical symptoms and radiological findings of lung cancer, proper diagnosis is necessary for TB and respiratory infections due to nontuberculousmycobacteria (NTM). Some of the drug resistive TB cases are, in fact, lung cancer or NTM lung infections. Acid-fast staining and histological study of phlegm and bronchial washing, culturing and polymerase chain reaction TB are among the most important solutions for differential diagnosis of these diseases. Briefly, it is assumed that TB is one of the risk factors for cancer. Numerous studies have been conducted in this regard throughout the world, and it has been observed that there is a significant relationship between previous TB infection and lung cancer. However, to prove this hypothesis, further and more extensive studies are required. In addition, as the clinical symptoms and radiological findings of TB, lung cancer, and non-TB mycobacteria lung infections are similar, they can be misdiagnosed as TB.

Keywords: TB and lung cancer, TB people, TB servivers, TB and HIV aids

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2265 Non-Signaling Chemokine Receptor CCRL1 and Its Active Counterpart CCR7 in Prostate Cancer

Authors: Yiding Qu, Svetlana V. Komarova

Abstract:

Chemokines acting through their cognate chemokine receptors guide the directional migration of the cell along the chemokine gradient. Several chemokine receptors were recently identified as non-signaling (decoy), based on their ability to bind the chemokine but produce no measurable signal in the cell. The function of these decoy receptors is not well understood. We examined the expression of a decoy receptor CCRL1 and a signaling receptor that binds to the same ligands, CCR7, in prostate cancer using publically available microarray data (www.oncomine.org). The expression of both CCRL1 and CCR7 increased in an approximately half of prostate carcinoma samples and the majority of metastatic cancer samples compared to normal prostate. Moreover, the expression of CCRL1 positively correlated with the expression of CCR7. These data suggest that CCR7 and CCRL1 can be used as clinical markers for the early detection of transformation from carcinoma to metastatic cancer. In addition, these data support our hypothesis that the non-signaling chemokine receptors actively stimulate cell migration.

Keywords: bioinformatics, cell migration, decoy receptor, meta-analysis, prostate cancer

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2264 PathoPy2.0: Application of Fractal Geometry for Early Detection and Histopathological Analysis of Lung Cancer

Authors: Rhea Kapoor

Abstract:

Fractal dimension provides a way to characterize non-geometric shapes like those found in nature. The purpose of this research is to estimate Minkowski fractal dimension of human lung images for early detection of lung cancer. Lung cancer is the leading cause of death among all types of cancer and an early histopathological analysis will help reduce deaths primarily due to late diagnosis. A Python application program, PathoPy2.0, was developed for analyzing medical images in pixelated format and estimating Minkowski fractal dimension using a new box-counting algorithm that allows windowing of images for more accurate calculation in the suspected areas of cancerous growth. Benchmark geometric fractals were used to validate the accuracy of the program and changes in fractal dimension of lung images to indicate the presence of issues in the lung. The accuracy of the program for the benchmark examples was between 93-99% of known values of the fractal dimensions. Fractal dimension values were then calculated for lung images, from National Cancer Institute, taken over time to correctly detect the presence of cancerous growth. For example, as the fractal dimension for a given lung increased from 1.19 to 1.27 due to cancerous growth, it represents a significant change in fractal dimension which lies between 1 and 2 for 2-D images. Based on the results obtained on many lung test cases, it was concluded that fractal dimension of human lungs can be used to diagnose lung cancer early. The ideas behind PathoPy2.0 can also be applied to study patterns in the electrical activity of the human brain and DNA matching.

Keywords: fractals, histopathological analysis, image processing, lung cancer, Minkowski dimension

Procedia PDF Downloads 176
2263 Assessing the Correlation between miR-141 Expression, Common K-Ras Gene Mutations, and Their Impact on Prognosis in Colorectal Cancer Tissue of Iranian Patients

Authors: Shima Behzadi

Abstract:

Background: In many human malignant tumors, microRNA expression is aberrant. This study investigates miR-141 as a prognostic marker in colorectal cancer with K-Ras mutation. Materials and methods: In this case-control study, 100 patients, mostly over the age of 50, who were diagnosed with colorectal cancer were selected. The pathology department of the Mostoufi Pathobiology and Genetics Laboratory in Tehran confirmed the presence of colorectal cancer in samples of paraffin-embedded colon tissue. The case group was composed of patients with codon 12 and 13 mutations in exon 2 of the K-Ras gene, while tumor samples of individuals without these mutations in exon 2 of the K-Ras gene were selected as the control group, with patient consent. The changes in the expression of miR-141 were examined in both groups. Results: The study found that 20% of the patients tested positive for codon 12 mutation, and 10% of patients had codon 13 mutation. As a result, in 30 cases, there was a higher level of miR-141 expression. The miR-141 gene expression level in K-Ras positive tumor samples was 1.5 times higher than its expression level in K-Ras negative samples. This increase in expression was statistically significant, with a p-value of less than 0.001, indicating that the observed results are highly statistically significant. Conclusion: The study revealed that the incidence of typical K-Ras gene mutations among the colorectal cancer patients in the sample matches the national average in Iran. Additionally, the expression of miR-141 can serve as a useful biomarker to aid in the prognosis of colorectal cancer.

Keywords: colorectal cancer, K-Ras gene, miR-141 marker, real time PCR, electrophoresis

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