Search results for: cancer cell apoptosis

Authors: Mir Mohammad Reza Hosseini

Abstract:

In new years immune checkpoint inhibitors have gathered care as being one of the greatest talented kinds of immunotherapy on the prospect. There has been a specific emphasis on the immune checkpoint molecules, cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed cell death protein 1 (PD-1). In 2011, ipilimumab, the primary antibody obstructive an immune checkpoint (CTLA4) was authorized. It is now documented that recognized tumors have many devices of overpowering the antitumor immune response, counting manufacture of repressive cytokines, staffing of immunosuppressive immune cells, and upregulation of coinhibitory receptors recognized as immune checkpoints. This was fast followed by the growth of monoclonal antibodies directing PD1 (pembrolizumab and nivolumab) and PDL1 (atezolizumab and durvalumab). Anti-PD1/PDL1 antibodies have developed some of the greatest extensively set anticancer therapies. We also compare and difference their present place in cancer therapy and designs of immune-related toxicities and deliberate the role of dual immune checkpoint inhibition and plans for the organization of immune-related opposing proceedings. In this review, the employed code and present growth of numerous immune checkpoint inhibitors are abridged, while the communicating device and new development of Immune checkpoint inhibitors in cancer therapy-based synergistic therapies with additional immunotherapy, chemotherapy, phototherapy, and radiotherapy in important and clinical educations in the historical 5 years are portrayed and tinted. Lastly, we disapprovingly measure these methods and effort to find their fortes and faintness based on pre-clinical and clinical information.

Keywords: checkpoint, cancer therapy, PD-1, PDL-1, CTLA4, immunosuppressive

Procedia PDF Downloads 145

Authors: Bhawna Chandravanshi, Ramesh Bhonde

Abstract:

In the present study, we focused on the improvisation of islet survival in hypoxia. The Islet-like cell aggregates (ICAs) derived from Wharton's jelly mesenchymal stem cells (WJ-MSC) were cultured with and without WJ-MSC for 48h in hypoxia and normoxia and tested for their direct trophic effect on β cell survival. The WJ MSCs themselves secreted insulin upon glucose challenge and expressed the pancreatic markers at both transcription and translational level (C-peptide, Insulin, Glucagon and Glut 2). Direct contact of MSCs with ICAs facilitate the highest viability under hypoxia as evidenced by fluorescein diacetate/propidium iodide and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The cytokine analysis of the co-cultured ICAs revealed amplification of anti-inflammatory cytokine-like TGFβ and TNFα accompanied by depletion of pro-inflammatory cytokines. The increment in VEGF and PDGFa was also seen showing their ability to vascularize upon transplantation. This was further accompanied by reduction in total reactive oxygen species, nitric oxide, and super oxide ions and down-regulation of Caspase3, Caspase8, p53 and up regulation of Bcl2 confirming prevention of apoptosis in ICAs. There was a significant reduction in the expression of p38 protein in the presence of MSCs making the ICAs responsive to glucose. Taken together our data demonstrate for the first time that the WJ-MSC expressed pancreatic markers and their supplementation protected engineered islets against hypoxia, oxidative stress, and inflammatory cytokines by inhibiting p38 MAPK protein.

Keywords: hypoxia, islet-like cell aggregates, inflammatory cytokines, oxidative stress

Procedia PDF Downloads 240

Authors: Sarah Crawford, Gerry Lesley

Abstract:

This research is a pre-clinical assessment of anti-cancer effects of novel non-steroidal diethyl stilbestrol-like estrogen analogs in estrogen-receptor positive/ progesterone-receptor positive human breast cancer microtumors of MCF 7 cell line. Tamoxifen analog formulation (Tam A1) was used as a single agent or in combination with therapeutic concentrations of 4-hydroxytamoxifen, currently used as a long-term treatment for the prevention of breast cancer recurrence in women with estrogen receptor positive/ progesterone receptor positive malignancies. At concentrations ranging from 30-50 microM, Tam A1 induced microtumor disaggregation and cell death. Incremental cytotoxic effects correlated with increasing concentrations of Tam A1. Live tumor microscopy showed that microtumos displayed diffuse borders and substrate-attached cells were rounded-up and poorly adherent. A complete cytotoxic effect was observed using 40-50 microM Tam A1 with time course kinetics similar to 4-hydroxytamoxifen. Combined treatment with TamA1 (30-50 microM) and 4-hydroxytamoxifen (10-15 microM) induced a highly cytotoxic, synergistic combined treatment response that was more rapid and complete than using 4-hydroxytamoxifen as a single agent therapeutic. Microtumors completely dispersed or formed necrotic foci indicating a highly cytotoxic combined treatment response. Moreover, breast cancer microtumors treated with both 4-hydroxytamoxifen and Tam A1 displayed lower levels of long-term post-treatment regrowth, a critical parameter of primary drug resistance, than observed for 4-hydroxytamoxifen when used as a single agent therapeutic. Tumor regrowth at 6 weeks post-treatment with either single agent 4-hydroxy tamoxifen, Tam A1 or a combined treatment was assessed for the development of drug resistance. Breast cancer cells treated with both 4-hydroxytamoxifen and Tam A1 displayed significantly lower levels of post-treatment regrowth, indicative of decreased drug resistance, than observed for either single treatment modality. The preclinical data suggest that combined treatment involving the use of tamoxifen analogs may be a novel clinical approach for long-term maintenance therapy in patients with estrogen-receptor positive/progesterone-receptor positive breast cancer receiving hormonal therapy to prevent disease recurrence. Detailed data on time-course, IC50 and tumor regrowth assays post- treatment as well as a proposed mechanism of action to account for observed synergistic drug effects will be presented.

Keywords: 4-hydroxytamoxifen, tamoxifen analog, drug-resistance, microtumors

Procedia PDF Downloads 46

Authors: Yao Song, Danni Cheng, Jianjun Ren

Abstract:

Objectives: We aimed to explore the prognostic effects of absolute values and dynamic changes of common hematological indices on oropharynx squamous cell carcinoma (OPSCC) patients treated with radiation. Methods and materials: The absolute values of white blood cell (WBC), absolute neutrophil count (ANC), absolute lymphocyte count (ALC), hemoglobin (Hb), platelet (Plt), albumin (Alb), neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) at baseline (within 45 days before radiation), 1-, 3-, 6- and 12-months after the start of radiotherapy were retrospectively collected. Locally-estimated smoothing scatterplots were used to describe the smooth trajectory of each index. A mixed-effect model with a random slope was fitted to describe the changing rate and trend of indices over time. Cox proportional hazard analysis was conducted to assess the correlation between hematological indices and treatment outcomes. Results: Of the enrolled 85 OPSCC patients, inflammatory indices, such as WBC and ALC, dropped rapidly during acute treatment and gradually recovered, while NLR and PLR increased at first three months and subsequently declined within 3-12 months. Higher absolute value or increasing trend of nutritional indices (Alb and Hb) was associated with better prognosis (all p<0.05). In contrast, patients with higher absolute value or upward trend of inflammatory indices (WBC, ANC, Plt, PLR and NLR) had worse survival (all p<0.05). Conclusions: The absolute values and dynamic changes of hematological indices were valuable prognostic factors for OPSCC patients who underwent radiotherapy.

Keywords: hematological indices, oropharyngeal cancer, radiotherapy, NLR, PLR

Procedia PDF Downloads 155

Authors: Karthik Mittal

Abstract:

This study performs an unsupervised machine learning analysis to find clusters of related SNPs which highlight biological pathways that are important for the biological mechanisms of breast cancer. Studying genetic variations in isolation is illogical because these genetic variations are known to modulate protein production and function; the downstream effects of these modifications on biological outcomes are highly interconnected. After extracting the SNPs and their effect on different types of breast cancer using the MRBase library, two unsupervised machine learning clustering algorithms were implemented on the genetic variants: a k-means clustering algorithm and a hierarchical clustering algorithm; furthermore, principal component analysis was executed to visually represent the data. These algorithms specifically used the SNP’s beta value on the three different types of breast cancer tested in this project (estrogen-receptor positive breast cancer, estrogen-receptor negative breast cancer, and breast cancer in general) to perform this clustering. Two significant genetic pathways validated the clustering produced by this project: the MAPK signaling pathway and the connection between the BRCA2 gene and the ESR1 gene. This study provides the first proof of concept showing the importance of unsupervised machine learning in interpreting GWAS summary statistics.

Keywords: breast cancer, computational biology, unsupervised machine learning, k-means, PCA

Procedia PDF Downloads 126

Authors: Lamis Naddaf, Yuval Tabach

Abstract:

In this research, we identified the missense genetic variants that have the potential to enhance resistance against cancer. Such field has not been widely explored, as researchers tend to investigate mutations that cause diseases, in response to the suffering of patients, rather than those mutations that protect from them. In conjunction with the genomic revolution, and the advances in genetic engineering and synthetic biology, identifying the protective variants will increase the power of genotype-phenotype predictions and can have significant implications on improved risk estimation, diagnostics, prognosis and even for personalized therapy and drug discovery. To approach our goal, we systematically investigated the sites of the coding genomes and picked up the alleles that showed a correlation with the species’ cancer resistance. We predicted 250 protecting variants (PVs) with a 0.01 false discovery rate and more than 20 thousand PVs with a 0.25 false discovery rate. Cancer resistance in Mammals and reptiles was significantly predicted by the number of PVs a species has. Moreover, Genes enriched with the protecting variants are enriched in pathways relevant to tumor suppression like pathways of Hedgehog signaling and silencing, which its improper activation is associated with the most common form of cancer malignancy. We also showed that the PVs are more abundant in healthy people compared to cancer patients within different human races.

Keywords: comparative genomics, machine learning, cancer resistance, cancer-protecting alleles

Procedia PDF Downloads 81

Authors: Grzegorz Raniszewski, Zbigniew Kolacinski, Lukasz Szymanski, Slawomir Wiak, Lukasz Pietrzak, Dariusz Koza

Abstract:

One of the most promising area for carbon nanotubes (CNTs) application is medicine. One of the most devastating diseases is cancer. Carbon nanotubes may be used as carriers of a slowly released drug. It is possible to use of electromagnetic waves to destroy cancer cells by the carbon nanotubes (CNTs). In our research we focused on thermal ablation by ferromagnetic carbon nanotubes (Fe-CNTs). In the cancer cell hyperthermia functionalized carbon nanotubes are exposed to radio frequency electromagnetic field. Properly functionalized Fe-CNTs join the cancer cells. Heat generated in nanoparticles connected to nanotubes warm up nanotubes and then the target tissue. When the temperature in tumor tissue exceeds 316 K the necrosis of cancer cells may be observed. Several techniques can be used for Fe-CNTs synthesis. In our work, we use high-temperature methods where arc-discharge is applied. Low-temperature systems are microwave plasma with assisted chemical vapor deposition (MPCVD) and hybrid physical-chemical vapor deposition (HPCVD). In the arc discharge system, the plasma reactor works with a pressure of He up to 0,5 atm. The electric arc burns between two graphite rods. Vapors of carbon move from the anode, through a short arc column and forms CNTs which can be collected either from the reactor walls or cathode deposit. This method is suitable for the production of multi-wall and single-wall CNTs. A disadvantage of high-temperature methods is a low purification, short length, random size and multi-directional distribution. In MPCVD system plasma is generated in waveguide connected to the microwave generator. Then containing carbon and ferromagnetic elements plasma flux go to the quartz tube. The additional resistance heating can be applied to increase the reaction effectiveness and efficiency. CNTs nucleation occurs on the quartz tube walls. It is also possible to use substrates to improve carbon nanotubes growth. HPCVD system involves both chemical decomposition of carbon containing gases and vaporization of a solid or liquid source of catalyst. In this system, a tube furnace is applied. A mixture of working and carbon-containing gases go through the quartz tube placed inside the furnace. As a catalyst ferrocene vapors can be used. Fe-CNTs may be collected then either from the quartz tube walls or on the substrates. Low-temperature methods are characterized by higher purity product. Moreover, carbon nanotubes from tested CVD systems were partially filled with the iron. Regardless of the method of Fe-CNTs synthesis the final product always needs to be purified for applications in medicine. The simplest method of purification is an oxidation of the amorphous carbon. Carbon nanotubes dedicated for cancer cell thermal ablation need to be additionally treated by acids for defects amplification on the CNTs surface what facilitates biofunctionalization. Application of ferromagnetic nanotubes for cancer treatment is a promising method of fighting with cancer for the next decade. Acknowledgment: The research work has been financed from the budget of science as a research project No. PBS2/A5/31/2013

Keywords: arc discharge, cancer, carbon nanotubes, CVD, thermal ablation

Procedia PDF Downloads 428

Authors: Bliss Singhal

Abstract:

Machine learning (ML) is a branch of Artificial Intelligence (AI) where computers analyze data and find patterns in the data. The study focuses on the detection of metastatic cancer using ML. Metastatic cancer is the stage where cancer has spread to other parts of the body and is the cause of approximately 90% of cancer-related deaths. Normally, pathologists spend hours each day to manually classifying whether tumors are benign or malignant. This tedious task contributes to mislabeling metastasis being over 60% of the time and emphasizes the importance of being aware of human error and other inefficiencies. ML is a good candidate to improve the correct identification of metastatic cancer, saving thousands of lives and can also improve the speed and efficiency of the process, thereby taking fewer resources and time. So far, the deep learning methodology of AI has been used in research to detect cancer. This study is a novel approach to determining the potential of using preprocessing algorithms combined with classification algorithms in detecting metastatic cancer. The study used two preprocessing algorithms: principal component analysis (PCA) and the genetic algorithm, to reduce the dimensionality of the dataset and then used three classification algorithms: logistic regression, decision tree classifier, and k-nearest neighbors to detect metastatic cancer in the pathology scans. The highest accuracy of 71.14% was produced by the ML pipeline comprising of PCA, the genetic algorithm, and the k-nearest neighbor algorithm, suggesting that preprocessing and classification algorithms have great potential for detecting metastatic cancer.

Keywords: breast cancer, principal component analysis, genetic algorithm, k-nearest neighbors, decision tree classifier, logistic regression

Procedia PDF Downloads 64

Authors: Lalita Subedi, Jae Kyoung Chae, Yong Un Park, Cho Kyo Hee, Lee Jae Hyuk, Kang Min Cheol, Sun Yeou Kim

Abstract:

Neuroinflammation may mediate the relationship between low levels of estrogens and neurodegenerative disease. Estrogens are neuroprotective and anti-inflammatory in neurodegenerative disease models. Due to the long term side effects of estrogens, researches have been focused on finding an effective phytoestrogens for biological activities. Daidzein present in soybeans and its active metabolite equol (7-hydroxy-3-(4'-hydroxyphenyl)-chroman) bears strong antioxidant and anticancer showed more potent anti-inflammatory and neuroprotective role in neuroinflammatory model confirmed its in vitro activity with molecular mechanism through NF-κB pathway. Three major CNS cells Microglia (BV-2), Astrocyte (C6), Neuron (N2a) were used to find the effect of equol in inducible nitric oxide synthase (iNOS), cyclooxygenase (COX-2), MAPKs signaling proteins, apoptosis related proteins by western blot analysis. Nitric oxide (NO) and prostaglandin E2 (PGE2) was measured by the Gries method and ELISA, respectively. Cytokines like tumor necrosis factor-α (TNF-α) and IL-6 were also measured in the conditioned medium of LPS activated cells with or without equol. Equol inhibited the NO production, PGE-2 production and expression of COX-2 and iNOS in LPS-stimulated microglial cells at a dose dependent without any cellular toxicity. At the same time Equol also showed promising effect in modulation of MAPK’s and nuclear factor kappa B (NF-κB) expression with significant inhibition of the production of proinflammatory cytokine like interleukin -6 (IL-6), and tumor necrosis factor -α (TNF-α). Additionally, it inhibited the LPS activated microglia-induced neuronal cell death by downregulating the apoptotic phenomenon in neuronal cells. Furthermore, equol increases the production of neurotrophins like NGF and increase the neurite outgrowth as well. In conclusion the natural daidzein metabolite equol are more active than daidzein, which showed a promising effectiveness as an anti-neuroinflammatory and neuroprotective agent via downregulating the LPS stimulated microglial activation and neuronal apoptosis. This work was supported by Brain Korea 21 Plus project and High Value-added Food Technology Development Program 114006-4, Ministry of Agriculture, Food and Rural Affairs.

Keywords: apoptosis, equol, neuroinflammation, phytoestrogen

Procedia PDF Downloads 348

Authors: Mrinal Kanti Bhowmik, Kakali Das Jr., Barin Kumar De, Debotosh Bhattacharjee

Abstract:

Breast cancer is the most common cancer and a leading cause of death for women in the 35 to 55 age group. Early detection of breast cancer can decrease the mortality rate of breast cancer. Mammography is considered as a ‘Gold Standard’ for breast cancer detection and a very popular modality, presently used for breast cancer screening and detection. The screening of digital mammograms often leads to over diagnosis and a consequence to unnecessary traumatic & painful biopsies. For that reason recent studies involving the use of thermal imaging as a screening technique have generated a growing interest especially in cases where the mammography is limited, as in young patients who have dense breast tissue. Tumor is a significant sign of breast cancer in both mammography and thermography. The tumors are complex in structure and they also exhibit a different statistical and textural features compared to the breast background tissue. Fractal geometry is a geometry which is used to describe this type of complex structure as per their main characteristic, where traditional Euclidean geometry fails. Over the last few years, fractal geometrics have been applied mostly in many medical image (1D, 2D, or 3D) analysis applications. In breast cancer detection using digital mammogram images, also it plays a significant role. Fractal is also used in thermography for early detection of the masses using the thermal texture. This paper presents an overview of the recent aspects and initiatives of fractals in breast cancer detection in both mammography and thermography. The scope of fractal geometry in automatic breast cancer detection using digital mammogram and thermogram images are analysed, which forms a foundation for further study on application of fractal geometry in medical imaging for improving the efficiency of automatic detection.

Keywords: fractal, tumor, thermography, mammography

Procedia PDF Downloads 367

Authors: Marta E. Hernandez-Caballero, Veronica Borgonio-Cuadra, Antonio Miranda-Duarte, Xochitl Rojas-Toledo, Normand Garcia-Hernandez, Maura Cardenas-Garcia, Teresa Abad-Camacho

Abstract:

Breast cancer (BC) is the most common tumor in women over the world. DNA methylation is an epigenetic modification critical in CpG sites, aberrant methylation of CpG islands in promoters is a hallmark of cancer. So, gene expression can be regulated by alterations in DNA methylation. In cell lines DACT2 gene reduces the growth and migration of tumor cells by its participation in the suppression of TGFb/SMAD2/3. PHF20L1 is involved in histone acetylation therefore, it regulates transcription. Our aim was to analyze the methylation status of the DACT2 and PHF20L1 promoter regions in tumoral and healthy mammary tissue from women with BC in different progression states. The study included 77 patients from Centro Medico Nacional La Raza in Mexico City. After identifying a CpG island in DACT2 and PHF20L1 promoters, DNA methylation status was analyzed through sodium bisulfite with subsequent amplification using methylation-specific PCR. Results revealed no changes in methylation status of PHF20L1 and cancer stages (II y III) or in comparison to healthy tissues, it was demethylated. DACT2 promoter methylation was no significant between tumoral stages (II, P = 0.37; III, P = 0.17) or with healthy tissue. Previous data reported DACT2 methylated in nasopharyngeal carcinoma but in this study promoter methylation was not observed. PHF20L1 protein contains N-terminal Tudor and C-terminal plant homeodomain domains, it has been suggested that can stabilize DNMT1 regulating DNA methylation, therefore, was associated with poor prognostic in BC. We found no evidence of methylation in patients and controls in PHF20L1 promoter, so its association with BC may have no direct relation with promoter methylation. More studies including other methylation sites in these genes in BC are necessary.

Keywords: bisulfite conversion, breast cancer, DACT2, DNA methylation, PHF20L1, tumoral status

Procedia PDF Downloads 278

Authors: Yelin Zhao, Xinxiu Li, Martin Smelik, Oleg Sysoev, Firoj Mahmud, Dina Mansour Aly, Mikael Benson

Abstract:

Background: Early diagnosis of pancreatic cancer is clinically challenging due to vague, or no symptoms, and lack of biomarkers. Polygenic risk score (PRS) scores may provide a valuable tool to assess increased or decreased risk of PC. This study aimed to develop such PRS by filtering genetic variants identified by GWAS using transcriptional programs identified by single-cell RNA sequencing (scRNA-seq). Methods: ScRNA-seq data from 24 pancreatic ductal adenocarcinoma (PDAC) tumor samples and 11 normal pancreases were analyzed to identify differentially expressed genes (DEGs) in in tumor and microenvironment cell types compared to healthy tissues. Pathway analysis showed that the DEGs were enriched for hundreds of significant pathways. These were clustered into 40 “programs” based on gene similarity, using the Jaccard index. Published genetic variants associated with PDAC were mapped to each program to generate program PRSs (pPRSs). These pPRSs, along with five previously published PRSs (PGS000083, PGS000725, PGS000663, PGS000159, and PGS002264), were evaluated in a European-origin population from the UK Biobank, consisting of 1,310 PDAC participants and 407,473 non-pancreatic cancer participants. Stepwise Cox regression analysis was performed to determine associations between pPRSs with the development of PC, with adjustments of sex and principal components of genetic ancestry. Results: The PDAC genetic variants were mapped to 23 programs and were used to generate pPRSs for these programs. Four distinct pPRSs (P1, P6, P11, and P16) and two published PRSs (PGS000663 and PGS002264) were significantly associated with an increased risk of developing PC. Among these, P6 exhibited the greatest hazard ratio (adjusted HR[95% CI] = 1.67[1.14-2.45], p = 0.008). In contrast, P10 and P4 were associated with lower risk of developing PC (adjusted HR[95% CI] = 0.58[0.42-0.81], p = 0.001, and adjusted HR[95% CI] = 0.75[0.59-0.96], p = 0.019). By comparison, two of the five published PRS exhibited an association with PDAC onset with HR (PGS000663: adjusted HR[95% CI] = 1.24[1.14-1.35], p < 0.001 and PGS002264: adjusted HR[95% CI] = 1.14[1.07-1.22], p < 0.001). Conclusion: Compared to published PRSs, scRNA-seq-based pPRSs may be used not only to assess increased but also decreased risk of PDAC.

Keywords: cox regression, pancreatic cancer, polygenic risk score, scRNA-seq, UK biobank

Procedia PDF Downloads 81

Authors: Sweta Agrawal, Sachin Chaugule, Gargi Rane, Shashank More, Madhavi Indap

Abstract:

Angiogenesis and metastasis are two of the most important hallmarks of cancer. Hence, most of the cancer therapies nowadays are multi-targeted so as to reduce resistance and have better efficacy. As synthetic molecules arise with a burden of their toxicities and side-effects, more and more research is being focussed on exploiting the vast natural resources of drugs, in the form of plants and animals. Although, the idea of using marine organisms as a source of pharmaceuticals is not new, the pace at which marine drugs are being discovered, has definitely up surged! In the present study, we have assessed the anti-angiogenic and in vitro anti-metastatic activity of aqueous fraction from the extract of marine gastropod Euchelus asper. The soft body of Euchelus Asper was extracted with methanol and named EAME. Partition chromatography of EAME gave three fractions EAME I, II and III. Biochemical analysis revealed the presence of proteins in EAME III. Preliminary analysis had revealed the anti-angiogenic activity was exhibited by EAME III out of the three fractions. Hereafter, EAME III (concentration 25µg/ml-400µg/ml) was tested on chick chorioallantoic membrane (CAM) model for the detailed analysis of its potential anti-angiogenic effect. In vitro testing of the fraction (concentration 0.25µg/ml - 1µg/ml), involved cytotoxicity by SRB assay, cell cycle analysis by flow cytometry and anti-proliferative effect by scratch wound healing assay on A549 lung carcinoma cells. Apart from this, a portion of treated CAM as well as conditioned medium from treated A549 were subjected to gelatin zymography for assessment of matrix metalloproteinases MMP-2 and MMP-9 levels. Our results revealed that EAME III exhibited significant anti-angiogenic activity on CAM which was also supported by histological observations. During histological studies of CAM, it was found that EAME III caused reduction in angiogenesis by altering the extracellular matrix of the CAM membrane. In vitro analysis disclosed that EAME III exhibited moderate cytotoxic effect on A549 cells and its effect was not dose-dependent. The results of flow cytometry confirmed that EAME III caused cell cycle arrest in A549 cell line as almost all of the treated cells were found in G1 phase. Further, the migration and proliferation of A549 was significantly reduced by EAME III as observed from the scratch wound assay. Moreover, Gelatin zymography analysis revealed that EAME III caused suppression of MMP-2 in CAM membrane and reduced MMP-9 and MMP-2 expression in A549 cells. This verified that the anti-angiogenic and anti-metastatic effects of EAME III were correlated with the suppression of MMP-2 and -9. To conclude, EAME III shows dual anti-tumour action by reducing angiogenesis and exerting anti-metastatic effect on lung cancer cells, thus it has the potential to be used as an anti-cancer agent against lung carcinoma.

Keywords: angiogenesis, anti-cancer, marine drugs, matrix metalloproteinases

Procedia PDF Downloads 208

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 297

Authors: Alka Yadav, Mayank Jain, Rajan Saxena, Niraj Kumari, Narendra Krishnani, Ashok Kumar

Abstract:

Purpose: To study the mismatch repair (MMR) protein expression and its clinicopathological correlation in colorectal cancer patients in North India. Methods: A prospective study was conducted on histologically proven 52 (38 males and 14 females) patients with adenocarcinoma of colorectum. MMR protein loss was determined by using immunohistochemistry for MLH1, MSH2, PMS2 and MSH6. Results: 52 patients (38 males and 14 females) underwent resection for colorectal cancer with the median age of 52 years (16-81 years). 35% of the patients (n=18) were younger than 50 years of the age. 3 patients had associated history of malignancy in the family. 29 (56%) patients had right colon cancer, 9 (17%) left colon cancer and 14 (27%) rectal cancer. 2 patients each had synchronous and metachronous cancer. Histology revealed well-differentiated tumour in 16, moderately differentiated in 10 and poorly differentiated tumour in 26 patients. MMR protein loss was seen in 15 (29%) patients. Seven (46%) of these patients were less than 50 years of age. Combined loss of MSH2 and MSH6 was seen most commonly and it was found in 6 patients. 12 (80%) patients with MMR protein loss had tumour located proximal to the splenic flexure compared to 3 (20%) located distal to the splenic flexure. There was no difference in MMR protein loss based on patients' age, gender, degree of tumour differentiation, stage of the disease and tumour histological characteristics. Conclusions: This study revealed that there was less than 30% MMR protein loss in colorectal cancer patients. The loss was most commonly seen in right sided colon cancer than left. A larger study is further required to validate these findings.

Keywords: colorectal cancer, mismatch repair protein, immunohitochemistry, clinicopathological correlation

Procedia PDF Downloads 202

Authors: Rana F. Obeidat, Suzanne S. Dickerson, Gregory G. Homish, Nesreen M. Alqaissi, Robin M. Lally

Abstract:

Background: Despite the fact that breast cancer is the most prevalent cancer among Jordanian women, practically nothing is known about their perceptions of early stage breast cancer and surgical treatment. Objective: To gain understanding of the diagnosis and surgical treatment experience of Jordanian women diagnosed with early stage breast cancer. Methods: An interpretive phenomenological approach was used for this study. A purposive sample of 28 Jordanian women who were surgically treated for early stage breast cancer within 6 months of the interview was recruited. Data were collected using individual interviews and analyzed using Heideggerian hermeneutical methodology. Results: Fear had a profound effect on Jordanian women’s stories of diagnosis and surgical treatment of early stage breast cancer. Women’s experience with breast cancer and its treatment was shaped by their pre-existing fear of breast cancer, the disparity in the quality of care at various health care institutions, and sociodemographic factors (e.g., education, age). Conclusions: Early after the diagnosis, fear was very strong and women lost perspective of the fact that this disease was treatable and potentially curable. To control their fears, women unconditionally trusted God, the health care system, surgeons, family, friends, and/or neighbors, and often accepted treatment offered by their surgeons without questioning. Implications for practice: Jordanian healthcare providers have a responsibility to listen to their patients, explore meanings they ascribe to their illness, and provide women with proper education and support necessary to help them cope with their illness.

Keywords: breast cancer, early stage, Jordanian, experience, phenomenology

Procedia PDF Downloads 309

Authors: Kefaya Qaddoum

Abstract:

The aim of this study is to predict breast cancer and to construct a supportive model that will stimulate a more reliable prediction as a factor that is fundamental for public health. In this study, we utilize general regression neural networks (GRNN) to replace the normal predictions with prediction periods to achieve a reasonable percentage of confidence. The mechanism employed here utilises a machine learning system called conformal prediction (CP), in order to assign consistent confidence measures to predictions, which are combined with GRNN. We apply the resulting algorithm to the problem of breast cancer diagnosis. The results show that the prediction constructed by this method is reasonable and could be useful in practice.

Keywords: neural network, conformal prediction, cancer classification, regression

Procedia PDF Downloads 265

Authors: Amar Ranjan, Julieana Durai, Pranay Tanwar

Abstract:

Background &Introduction: Ovarian cancer is one of the most common malignant tumor in the female. 70% of the cases of ovarian cancer are diagnosed at an advanced stage. The five-year survival rate associated with ovarian cancer is less than 30%. The early diagnosis of ovarian cancer becomes a key factor in improving the survival rate of patients. Presently, CAl25 (carbohydrate antigen125) is used for the diagnosis and therapeutic monitoring of ovarian cancer, but its sensitivity and specificity is not ideal. The introduction of HE4, human epididymis protein 4 has attracted much attention. HE4 has a sensitivity and specificity of 72.9% and 95% for differentiating between benign and malignant adnexal masses, which is better than CA125 detection.  Methods: Serum HE4 and CA -125 were estimated using the chemiluminescence method. Our cases were 40 epithelial ovarian cancer, 9 benign ovarian tumor, 29 benign gynaecological diseases and 13 healthy individuals. This group include healthy woman those who have undergoing family planning and menopause-related medical consultations and they are negative for ovarian mass. Optimal cut off values for HE4 and CA125 were 55.89pmol/L and 40.25U/L respectively (determined by statistical analysis). Results: The level of HE4 was raised in all ovarian cancer patients (n=40) whereas CA125 levels were normal in 6/40 ovarian cancer patients, which were the cases of OC confirmed by histopathology. There is a significant decrease in the level of HE4 with comparison to CA125 in benign ovarian tumor cases. Both the levels of HE4 and CA125 were raised in the nonovarian cancer group, which includes cancer of endometrium and cervix. In the healthy group, HE4 was normal in all patients except in one case of the rudimentary horn, and the reason for this raised HE4 level is due to the incomplete development of uterus whereas CA125 was raised in 3 cases. Conclusions: Findings showed that the serum level of HE4 is an important indicator in the diagnosis of ovarian cancer, and it also distinguishes between benign and malignant pelvic masses. However, a combination of HE4 and CA125 panel will be extremely valuable in improving the diagnostic efficiency of ovarian cancer. These findings of our study need to be validated in the larger cohort of patients.

Keywords: human epididymis protein 4, ovarian cancer, diagnosis, benign lesions

Procedia PDF Downloads 110

Authors: Celso Afonso Klein Jr., Henrique Cantarelli, Fernando Portella, Keiichi Hosaka, Eduardo Reston, Fabricio Collares, Roberto Zimmer

Abstract:

TTo evaluate the influence of preheating self-adhesive cement at 39ºC on cell migration, cytotoxicity and degree of conversion. RelyX U200, Set PP and MaxCem Elite were subjected to a degree of conversion analysis (FTIR-ATR). For the cytotoxicity analysis, extracts (24 h and 7 days) were placed in contact with NIH/3T3 cells. For cell migration, images were captured of each sample until the possible closure of the cleft occurred. In the results of the degree of conversion, preheating did not improve the conversion of cement. For the MTT, preheating did not improve the results within 24 hours. However, it generated positive results within 7 days for the Set PP resin cement. For cell migration, high rates of cell death were found in all groups. It is concluded that preheating at 39ºC caused a positive effect only in increasing the cell viability of the Set PP resin cement and that both materials analyzed are highly cytotoxic.

Keywords: dental cements, resin cements, degree of conversion, cytotoxicity, cell migration assays

Procedia PDF Downloads 45

Authors: Hung Lin-Zin, Lai Mei-Yen

Abstract:

Prostate cancer is the most commonly diagnosed male cancer in the U.S. The prevalence is around 1 in 8. The etiology of prostate cancer is still unknown, but some predisposing factors, such as age, black race, family history, and obesity, may increase the risk of the disease. In 2020, a total of 7,178 Taiwanese people were nearly diagnosed with prostate cancer, accounting for 5.88% of all cancer cases, and the incidence rate ranked fifth among men. In that year, the total number of deaths from prostate cancer was 1,730, accounting for 3.45% of all cancer deaths, and the death rate ranked 6th among men, accounting for 94.34% of the cases of male reproductive organs. Looking for domestic and foreign literature on the use of OMOP (Observational Medical Outcomes Partnership, hereinafter referred to as OMOP) database analysis, there are currently nearly a hundred literature published related to nursing-related health problems and nursing measures built in the OMOP general data model database of medical institutions are extremely rare. The OMOP common data model construction analysis platform is a system developed by the FDA in 2007, using a common data model (common data model, CDM) to analyze and monitor healthcare data. It is important to build up relevant nursing information from the OMOP- CDM database to assist our daily practice. Therefore, we choose prostate cancer patients who are our popular care objects and use the OMOP- CDM database to explore the common associated health problems. With the assistance of OMOP-CDM database analysis, we can expect early diagnosis and prevention of prostate cancer patients' comorbidities to improve patient care.

Keywords: OMOP, nursing diagnosis, health problem, prostate cancer

Procedia PDF Downloads 38

Authors: Sahar Nasr, Lin Li, Edwin Wang

Abstract:

Bladder cancer (BLCA) is known as the 13th cause of death among cancer patients worldwide, and ~575,000 new BLCA cases are diagnosed each year. Urothelial carcinoma (UC) is the most prevalent subtype among BLCA patients, which can be categorized into muscle-invasive bladder cancer (MIBC) and non-muscle-invasive bladder cancer (NMIBC). Currently, various therapeutic options are available for UC patients, including (1) transurethral resection followed by intravesical instillation of chemotherapeutics or Bacillus Calmette-Guérin for NMIBC patients, (2) neoadjuvant platinum-based chemotherapy (NAC) plus radical cystectomy is the standard of care for localized MIBC patients, and (3) systematic chemotherapy for metastatic UC. However, conventional treatments may lead to several challenges for treating patients. As an illustration, some patients may suffer from recurrence of the disease after the first line of treatment. Recently, immune checkpoint therapy (ICT) has been introduced as an alternative treatment strategy for the first or second line of treatment in advanced or metastatic BLCA patients. Although ICT showed lucrative results for a fraction of BLCA patients, ~80% of patients were not responsive to it. Therefore, novel treatment methods are required to augment the ICI response rate within BLCA patients. It has been shown that the infiltration of T-cells into the tumor microenvironment (TME) is positively correlated with the response to ICT within cancerous patients. Therefore, the goal of this study is to enhance the infiltration of cytotoxic T-cells into TME through the identification of target genes within the tumor that are responsible for the non-T-cell inflamed TME and their inhibition. BLCA bulk RNA-sequencing data from The Cancer Genome Atlas (TCGA) and immune score for TCGA samples were used to determine the Pearson correlation score between the expression of different genes and immune score for each sample. The genes with strong negative correlations were selected (r < -0.2). Thereafter, the correlation between the expression of each gene and survival in BLCA patients was calculated using the TCGA data and Cox regression method. The genes that are common in both selected gene lists were chosen for further analysis. Afterward, BLCA bulk and single-cell RNA-sequencing data were ranked based on the expression of each selected gene and the top and bottom 25% samples were used for pathway enrichment analysis. If the pathways related to the T-cell infiltration (e.g., antigen presentation, interferon, or chemokine pathways) were enriched within the low-expression group, the gene was included for downstream analysis. Finally, the selected genes will be used to calculate the correlation between their expression and the infiltration rate of the activated CD+8 T-cells, natural killer cells and the activated dendric cells. A list of potential target genes has been identified and ranked based on the above-mentioned analysis and criteria. SUN-1 got the highest score within the gene list and other identified genes in the literature as benchmarks. In conclusion, inhibition of SUN1 may increase the tumor-infiltrating lymphocytes and the efficacy of ICI in BLCA patients. BLCA tumor cells with and without SUN-1 CRISPR/Cas9 knockout will be injected into the syngeneic mouse model to validate the predicted SUN-1 effect on increasing tumor-infiltrating lymphocytes.

Keywords: data analysis, gene expression analysis, gene identification, immunoinformatic, functional genomics, transcriptomics

Procedia PDF Downloads 138

Authors: Abdulkader Helwan

Abstract:

Iris cancer, so called intraocular melanoma is a cancer that starts in the iris; the colored part of the eye that surrounds the pupil. There is a need for an accurate and cost-effective iris cancer detection system since the available techniques used currently are still not efficient. The combination of the image processing and artificial neural networks has a great efficiency for the diagnosis and detection of the iris cancer. Image processing techniques improve the diagnosis of the cancer by enhancing the quality of the images, so the physicians diagnose properly. However, neural networks can help in making decision; whether the eye is cancerous or not. This paper aims to develop an intelligent system that stimulates a human visual detection of the intraocular melanoma, so called iris cancer. The suggested system combines both image processing techniques and neural networks. The images are first converted to grayscale, filtered, and then segmented using prewitt edge detection algorithm to detect the iris, sclera circles and the cancer. The principal component analysis is used to reduce the image size and for extracting features. Those features are considered then as inputs for a neural network which is capable of deciding if the eye is cancerous or not, throughout its experience adopted by many training iterations of different normal and abnormal eye images during the training phase. Normal images are obtained from a public database available on the internet, “Mile Research”, while the abnormal ones are obtained from another database which is the “eyecancer”. The experimental results for the proposed system show high accuracy 100% for detecting cancer and making the right decision.

Keywords: iris cancer, intraocular melanoma, cancerous, prewitt edge detection algorithm, sclera

Procedia PDF Downloads 480

Authors: Alejandra Betancur Sánchez, Carmen Elena Zapata Sánchez, Juan Bautista López Ortiz

Abstract:

Adverse effects and increased air pollution has raised concerns about regulatory policies and has fostered the development of new air quality standards; this is due to the complexity of the composition and the poorly understood reactions in the atmospheric environment. Toxic compounds act as environmental agents having various effects, from irritation to death of cells and tissues. A toxic agent is defined an adverse response in a biological system. There is a particular class that produces some kind of alteration in the genetic material or associated components, so they are recognized as genotoxic agents. Within cells, they interact directly or indirectly with DNA, causing mutations or interfere with some enzymatic repair processes or in the genesis or polymerization of proteinaceous material involved in chromosome segregation. An air pollutant may cause or contribute to increased mortality or serious illness and even pose a potential danger to human health. The aim of this study was to evaluate the effect on the viability and the genotoxic potential on the cell lines CHO-K1 and Jurkat and peripheral blood of particulate matter PM T lymphocytes 2.5 obtained from filters collected three monitoring stations network air quality Aburrá Valley. Tests, reduction of MTT, trypan blue, NRU, comet assay, sister chromatid exchange (SCE) and chromosomal aberrations allowed evidence reduction in cell viability in cell lines CHO-K1 and Jurkat and damage to the DNA from cell line CHOK1, however, no significant effects were observed in the number of SCEs and chromosomal aberrations. The results suggest that PM2.5 material has genotoxic potential and can induce cancer development, as has been suggested in other studies.

Keywords: PM2.5, cell line Jurkat, cell line CHO-K1, cytotoxicity, genotoxicity

Procedia PDF Downloads 245

Authors: Vidia A. Nuraini, Eugene M. H. Yee, Mohan Bhadbhade, David StC. Black, Naresh Kumar

Abstract:

Flavonoids are naturally occurring compounds that have been shown to exhibit a wide range of biological properties including anticancer and anti-inflammatory activities. However, flavonoids suffer from low bioavailability, which limits their overall utility for therapeutic applications. One of the methods to overcome this limitation is through structural modification of natural flavonoids. In this study, flavanone, isoflavanone, and isoflavene, were structurally modified through the introduction of additional fused-ring systems via ortho-quinone methide intermediates (o-QMs). These intermediates can readily undergo a [4+2] cycloaddition through an inverse-electron-demand Diels–Alder reaction with electron-rich dienophiles. A regioselective Mannich reaction using bis-(N,N-dimethylamino)methane was employed to generate the o-QM precursors of flavanone, isoflavanone, and isoflavene. The o-QM intermediates were subsequently generated in situ through thermal elimination of the dimethylamine functionality and reacted with a variety of dienophiles to produce novel flavonoids with fused-ring systems. A total of 21 novel flavonoid analogs were successfully synthesized. The X-ray crystal structure of cycloaddition adducts, particularly those derived from 3,4-dihydro-2H-pyran and p-methoxystyrene revealed a special case of enantiomeric disorder, where two enantiomers in equal amounts superpose with one another, with the exception for atoms that have opposite configuration. The anticancer properties of fused-ring systems derived from isoflavene were evaluated against the neuroblastoma SKN-BE(2)C, the triple negative breast cancer MDA-MB-231, and the glioblastoma U87 cancer cell lines. One of these cycloaddition adducts had displayed improved anti-proliferative activity against MDA-MB-231 and U87 cancer cell lines as compared to the parent compound. Further anticancer and anti-inflammatory activities of the flavanone and isoflavanone analogs are currently being investigated.

Keywords: Diels-Alder reaction, flavonoids, Mannich reaction, ortho-quinone methide.

Procedia PDF Downloads 230

Authors: Jaewoo Choi, Ki-Tae Hwang, Eunyoung Ko

Abstract:

Backgrounds/Aims: Patients with breast cancer are currently classified according to TNM stage. Nevertheless, the actual volume would be mis-estimated, and it would bring on inappropriate diagnosis. Tridimensional volume-stage derived from the ellipsoid formula was presented as useful measure. Methods: The medical records of 480 consecutive breast cancer between January 2001 and March 2013 were retrospectively reviewed. All patients were divided into three groups according to tumor volume by receiver operating characteristic analysis, and the ranges of each volume-stage were that V1 was below 2.5 cc, V2 was exceeded 2.5 and below 10.9 cc, and V3 was exceeded 10.9 cc. We analyzed outcomes of volume-stage and compared disease-free survival (DFS) and overall survival (OS) between size-stage and volume-stage with variant intrinsic factor. Results: In the T2 stage, there were patients who had a smaller volume than 4.2 cc known as maximum value of T1. These findings presented that patients in T1c had poorer DFS than T2-lesser (mean of DFS 48.7 vs. 51.8, p = 0.011). Such is also the case in OS (mean of OS 51.1 vs. 55.3, p = 0.006). The cumulative survival curves for V1, V2 compared T1, T2 showed similarity in DFS (HR 1.9 vs. 1.9), and so did it for V3 compared T3 (HR 3.5 vs. 2.6) significantly. Conclusion: This study demonstrated that tumor volume had good feasibility on the prognosis of patients with breast cancer. We proposed that volume-stage should be considered for an additional stage indicator, particularly in early breast cancer.

Keywords: breast cancer, tridimensional volume of tumor, TNM stage, volume stage

Procedia PDF Downloads 384

Authors: Isha Ranadive, Sonam Patel, Suresh Balakrishnan

Abstract:

It has been observed that in lizards wound can be healed by either a scar free mechanism or by scarring. The animal model used to study both these healing processes was Northern House Gecko. In lizard, the tail when amputated heals by scar free mechanism which allows it to regenerate, the same is not seen when the limb is amputated. Proliferation, apoptosis, and angiogenesis are the main events which succeed an injury. We observed that proliferation of the cells beneath the wound epidermis was much higher in case of wound healing in tail. This could be because after the wound gets covered by the epithelium, it enters in to a cross-talk with the underlying mesenchyme to recruit a pool of blastemal cells which proliferate and later differentiate to form the lost part through epimorphic regeneration. This was substantiated by mRNA expression levels of various FGFs which facilitate the cross-talk and also by PCNA which is a marker for proliferation. Western blot result reaffirms the same notion. However, in case of the limb, the rate of apoptosis was more than proliferation as there are a lot of debris that needs to be removed. We came to this conclusion as we observed that p53 the apoptotic gene was highly upregulated in case of the scarred tissue. Further, we confirmed this result by checking the anti-apoptotic gene bcl2 and found it to be significantly down-regulated. As we noticed heightened proliferation in the case of scar-free wound healing in tail, angiogenesis was targeted for the study. This is because, when the cells are proliferating they require constant supply of blood and hence neo-vascularization is inevitable. It was observed that the marker of angiogenesis, VEGF, was expressed more during wound healing as compared to the resting stage of tail. Moreover, a high up-regulation was seen in KDR, a receptor of VEGF. Thus, this study reveals how proliferation, apoptosis, and angiogenesis play a key role in the scar-free as well as scarred wound healing.

Keywords: epimorphic regeneration, injury, northern house gecko, wound healing

Procedia PDF Downloads 227

Authors: Padma Sree Potru

Abstract:

Abstract: A co-relational descriptive study was conducted to assess the impact of cancer event on self, on family, coping strategies of cancer clients and quality of life among them in G.G.H., Guntur, Andhra Pradesh, India. Aim: The aim of the study was to investigate the impact of cancer events on self, on family, coping of clients and quality of life among cancer patients. Methods: 50 cancer patients were selected through random sampling technique. The data were obtained by using impact of events scale, impact on family scale, coping health inventory and WHOQOL-BREF scale. Results: The results revealed that majority (32%) of them were in the age group of 36-45 years, 72% were females, 44% were having the income of Rs. 5001-10000/- per month, 40% were working for daily wage, and 15% were newly diagnosed of cancer. Among 50 cancer patients, 65% had extreme impact of events, 61% shows extreme impact on family, 46% possess minimal coping strategies and 68% had poor quality of life. This study focuses on that there is a strong positive correlation between quality of life and coping behavior r=0.603 and also between impact of event and impact on family r=0.610, but a negative correlation existed between quality of life and impact of events r= -0.201. ANOVA test reveals that there is a significant difference between subscales of impact on family and coping behavior with f values = 3.893, 3.957 respectively. Chi-square highlights that there is a significant association between impact of events with age, occupation and impact on family with duration of illness. Conclusion: Even though cancer is a dreadful disease still there are many emerging treatment modalities and innovative procedures which are focusing on improving the standards of life among cancer clients. But all this can happen only when the clients accepts the reality, increase their willpower and confidence, desire to live, focusing on coping mechanisms and good ongoing support from the family members.

Keywords: impact of event, impact on family, coping, quality of event

Procedia PDF Downloads 425

Authors: Rajvir Kaur, Jeewani Anupama Ginige

Abstract:

With recent trends in Big Data and advancements in Information and Communication Technologies, the healthcare industry is at the stage of its transition from clinician oriented to technology oriented. Many people around the world die of cancer because the diagnosis of disease was not done at an early stage. Nowadays, the computational methods in the form of Machine Learning (ML) are used to develop automated decision support systems that can diagnose cancer with high confidence in a timely manner. This paper aims to carry out the comparative evaluation of a selected set of ML classifiers on two existing datasets: breast cancer and cervical cancer. The ML classifiers compared in this study are Decision Tree (DT), Support Vector Machine (SVM), k-Nearest Neighbor (k-NN), Logistic Regression, Ensemble (Bagged Tree) and Artificial Neural Networks (ANN). The evaluation is carried out based on standard evaluation metrics Precision (P), Recall (R), F1-score and Accuracy. The experimental results based on the evaluation metrics show that ANN showed the highest-level accuracy (99.4%) when tested with breast cancer dataset. On the other hand, when these ML classifiers are tested with the cervical cancer dataset, Ensemble (Bagged Tree) technique gave better accuracy (93.1%) in comparison to other classifiers.

Keywords: artificial neural networks, breast cancer, classifiers, cervical cancer, f-score, machine learning, precision, recall

Procedia PDF Downloads 260

Authors: Yen-Hao Su, Wan-Chun Tang, Ya-Wen Cheng, Peik Sia, Chi-Chen Huang, Yi-Chao Lee, Hsin-Yi Jiang, Ming-Heng Wu, I-Lu Lai, Jun-Wei Lee, Kuen-Haur Lee

Abstract:

There is a wide range of drugs and combinations under investigation and/or approved over the last decade to treat colorectal cancer (CRC), but the 5-year survival rate remains poor at stages II–IV. Therefore, new, more efficient drugs still need to be developed that will hopefully be included in first-line therapy or overcome resistance when it appears, as part of second- or third-line treatments in the near future. In this study, we revealed that heat shock protein 90 (Hsp90) inhibitors have high therapeutic potential in CRC according to combinative analysis of NCBI's Gene Expression Omnibus (GEO) repository and chemical genomic database of Connectivity Map (CMap). We found that second generation Hsp90 inhibitor, NVP-AUY922, significantly down regulated the activities of a broad spectrum of kinases involved in regulating cell growth arrest and death of NVPAUY922-sensitive CRC cells. To overcome NVP-AUY922-induced upregulation of survivin expression which causes drug insensitivity, we found that combining berberine (BBR), a herbal medicine with potency in inhibiting survivin expression, with NVP-AUY922 resulted in synergistic antiproliferative effects for NVP-AUY922-sensitive and -insensitive CRC cells. Furthermore, we demonstrated that treatment of NVP-AUY922-insensitive CRC cells with the combination of NVP-AUY922 and BBR caused cell growth arrest through inhibiting CDK4 expression and induction of microRNA-296-5p (miR-296-5p)-mediated suppression of Pin1–β-catenin–cyclin D1 signaling pathway. Finally, we found that the expression level of Hsp90 in tumor tissues of CRC was positively correlated with CDK4 and Pin1 expression levels. Taken together, these results indicate that combination of NVP-AUY922 and BBR therapy can inhibit multiple oncogenic signaling pathways of CRC.

Keywords: berberine, colorectal cancer, connectivity map, heat shock protein 90 inhibitor

Procedia PDF Downloads 290

Authors: Chiou-Fang Liou

Abstract:

Cancer has been one of the most life-threaten diseases worldwide for 30+ years. The influences of cancer illness include symptoms from cancer itself along with its treatments. The quality of life among patients diagnosed with cancer during cancer treatments has been conceptualized within four domains: Functional Well-Being, Social Well-Being, Physical Well-Being, and Emotional Well-Being. Patients with cancer often need to make adjustments to face all the challenges. The middle-range theory of Resourcefulness and Quality of life has been applied to explore factors contributing to cancer patients’ needs. Resourcefulness is defined as sets of skills that can be learned and consisted of Person and Social Resourcefulness. Empirical evidence also supported a possible relationship between Resourcefulness and Quality of Life. However, little is known about the extent to which the two concepts are related to each other. This study, therefore, applied a multivariate technique, Canonical Correlation Analysis, to identify the relationship between the two sets of variables with multi-dimensional measures, the Resourcefulness and Quality of Life in Cancer patients receiving treatments. After IRB approval, this multi-centered study took place at two medical centers in the Central Region of Taiwan. Sample A total of 186 patients with various cancer diagnoses and either receiving radiation therapy or chemotherapy consented to and answered questionnaires. The Import findings of the Generalized F test identified two typical sets with several linear relations and explained a total of 79.1% of the total variance. The first typical set found Personal Resourcefulness negatively related to Social Well-being, Functional being, Emotional Well-being, and Physical, in that order. The second typical set found Social Resourcefulness negatively related to Functional Well-being and Physical-being yet positively related to Social Well-being and Emotional Well-being. Discussion and Conclusion, The results of this presented study supported the statistically significant relationship between two sets of variables that are consistent with the theory. In addition, the results are considerably important in cancer patients receiving cancer treatments.

Keywords: cancer, canonical correlation analysis, quality of life, resourcefulness

Procedia PDF Downloads 64