Search results for: molecular mechanisms of cancer

Authors: Ramandeep Kaur, Gurjit Singh Bhathal

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Cancer diagnosis is very difficult task. Magnetic resonance imaging (MRI) scan is used to produce image of any part of the body and provides an efficient way for diagnosis of cancer or tumor. In existing method, fuzzy clustering mean (FCM) is used for the diagnosis of the tumor. In the proposed method FCM is used to diagnose the cancer of the foot. FCM finds the centroids of the clusters of the foot cancer obtained from MRI images. FCM thresholding result shows the extract region of the cancer. Morphological operations are applied to get extracted region of cancer.

Keywords: magnetic resonance imaging (MRI), fuzzy C mean clustering, segmentation, morphological operations

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Authors: Nadia Naseem, Farwa Batool, Nasir Mehmood, AbdulHannan Nagi

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Background: The incidence and mortality of breast cancer vary significantly in geographically distinct populations. In Pakistan, breast cancer has shown an increase in incidence in young females and is characterized by more aggressive behavior. The tumor suppressor TP53 gene is a crucial genetic factor that plays a significant role in breast carcinogenesis. This study investigated the TP53 mutations in molecular subtypes of both nodes negative and positive breast cancer in young Pakistani patients. Material and Methods: p53, Estrogen Receptor (ER), Progesterone Receptor (PR), Her-2 neu and Ki 67 expressions were analyzed immunohistochemically in a series of 75 node negative (A) and 75 node positive (B) young (aged: 19-40 years) breast cancer patients diagnosed between 2014 to 2017 at two leading hospitals of Punjab, Pakistan. Tumor tissue specimens and peripheral blood samples were examined for TP53 mutations by direct sequencing of the gene (exons 4-9). The relation of TP53 mutations to these markers and clinicopathological data was investigated. Results: Mean age of the patients was 32.4 + 9.1 SD. Invasive breast carcinoma was the most frequent histological variant (A=92%, B=94.6%). Grade 3 carcinoma was the commonest grade (A=72%, B=81.3%). Triple negative cases (ER-, PR-, Her-2) formed most of the molecular subtypes (A=44%, B=50.6%). A total of 17.2% (A: 6.6%, B: 10.6%) patients showed TP53 mutations. Mutations were significantly more frequent in triple negative cases (A: 74.8%, B: 62.2%) compared to HER2-positive patients (P < 0.0001). In the multivariate analysis of the whole patient group, the independent prognosticator were triple negative cases (P=0.021), TP53 overexpression by IHC (P=0.001) and advanced-stage disease (P=0.007). No statistically significant correlation between TP53 mutations and clinicopathological parameters was found (P < 0.05). Conclusions: It is concluded that TP53 mutations are infrequently present in breast carcinoma of young Pakistani population and there was no significant correlation between p53 mutation and early onset disease. Immunohistochemically detected TP53 expression in our resource-constrained to set up can be beneficial in predicting mutations at the younger age in our population.

Keywords: immunohistochemistry (IHC), invasive breast carcinoma (IBC), Pakistan, TP53

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Authors: Michael Aupetit, Mahmoud Al-ismail, Khaled Mohamed

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Cancer is a major public health problem all over the world. Breast cancer has the highest incidence rate over all cancers for women in Qatar making its study a top priority of the country. Human cancer is a dynamic disease that develops over an extended period through the accumulation of a series of genetic alterations. A Darwinian process drives the tumor cells toward higher malignancy growing the branches of a progression tree in the space of genes expression. Although it is not possible to track these genetic alterations dynamically for one patient, it is possible to reconstruct the progression tree from the aggregation of thousands of tumor cells’ genetic profiles from thousands of different patients at different stages of the disease. Analyzing the progression tree is a way to detect pivotal molecular events that drive the malignant evolution and to provide a guide for the development of cancer diagnostics, prognostics and targeted therapeutics. In this work we present the development of a Visual Analytic web platform CanVis enabling users to upload gene-expression data and analyze their progression tree. The server computes the progression tree based on state-of-the-art techniques and allows an interactive visual exploration of this tree and the gene-expression data along its branching structure helping to discover potential driver genes.

Keywords: breast cancer, progression tree, visual analytics, web platform

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Authors: Asif Bilal, Fouzia Tanvir, Sibtain Ahmad

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Estrogen receptor alpha, also known as estrogen receptor-1, is highly involved in risk of mammary carcinoma. The objectives of this study were to identify non-synonymous SNPs of estrogen receptor and their association with breast cancer and to identify the chemotherapeutic responses of phytochemicals against it via in-silico study design. For this purpose, different online tools. to identify pathogenic SNPs the tools were SIFT, Polyphen, Polyphen-2, fuNTRp, SNAP2, for finding disease associated SNPs the tools SNP&GO, PhD-SNP, PredictSNP, MAPP, SNAP, MetaSNP, PANTHER, and to check protein stability Mu-Pro, I-Mutant, and CONSURF were used. Post-translational modifications (PTMs) were detected by Musitedeep, Protein secondary structure by SOPMA, protein to protein interaction by STRING, molecular docking by PyRx. Seven SNPs having rsIDs (rs760766066, rs779180038, rs956399300, rs773683317, rs397509428, rs755020320, and rs1131692059) showing mutations on I229T, R243C, Y246H, P336R, Q375H, R394S, and R394H, respectively found to be completely deleterious. The PTMs found were 96 times Glycosylation; 30 times Ubiquitination, a single time Acetylation; and no Hydroxylation and Phosphorylation were found. The protein secondary structure consisted of Alpha helix (Hh) is (28%), Extended strand (Ee) is (21%), Beta turn (Tt) is 7.89% and Random coil (Cc) is (44.11%). Protein-protein interaction analysis revealed that it has strong interaction with Myeloperoxidase, Xanthine dehydrogenase, carboxylesterase 1, Glutathione S-transferase Mu 1, and with estrogen receptors. For molecular docking we used Asiaticoside, Ilekudinuside, Robustoflavone, Irinoticane, Withanolides, and 9-amin0-5 as ligands that extract from phytochemicals and docked with this protein. We found that there was great interaction (from -8.6 to -9.7) of these ligands of phytochemicals at ESR1 wild and two mutants (I229T and R394S). It is concluded that these SNPs found in ESR1 are involved in breast cancer and given phytochemicals are highly helpful against breast cancer as chemotherapeutic agents. Further in vitro and in vivo analysis should be performed to conduct these interactions.

Keywords: breast cancer, ESR1, phytochemicals, molecular docking

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Authors: Nesreen M. Alqaissi

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Little is known about the lived experiences of breast cancer among Arab Muslim women. The researcher used a qualitative interpretive phenomenological research design to explore the lived experiences of breast cancer as described by Jordanian Muslim women. A purposive sample of 20 women with breast cancer was recruited. Data were collected utilizing individual semi-structured interviews, and analyzed using Heideggerian Hermeneutical methodology. Results: Five related themes and one constitutive pattern: (a) breast cancer means death; (b) matriarchal family members as important source of support; (c) spirituality as a way to live and survive breast cancer; (d) concealing cancer experiences to protect self and families; (e) physicians as protectors and treatment decision makers; (f) the constitutive pattern: culture influencing Jordanian women experiences with breast cancer. In conclusion, researchers and healthcare providers should consider the influence of culture, spirituality, and families, when caring for women with breast cancer from Jordan.

Keywords: breast cancer, Arab Muslim, Jordan, lived experiences, spirituality, culture

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Authors: Sahar Heidary

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Breast cancer is a main public common obstacle global. Additionally, it is the second top reason for tumor death across women. Considering breast cancer cure choices can aid private doctors in precaution for their patients through future cancer treatment. This article reviews usual management centered on stage, histology, and biomarkers. The growth of breast cancer is a multi-stage procedure including numerous cell kinds and its inhibition residues stimulating in the universe. Timely identification of breast cancer is one of the finest methods to stop this illness. Entirely chief therapeutic administrations mention screening mammography for women aged 40 years and older. Breast cancer metastasis interpretations for the mainstream of deaths from breast cancer. The discovery of breast cancer metastasis at the initial step is essential for managing and estimate of breast cancer development. Developing methods consuming the exploration of flowing cancer cells illustrate talented outcomes in forecasting and classifying the initial steps of breast cancer metastasis in patients. In public, mammography residues are the key screening implement though the efficiency of medical breast checks and self-checkup is less. Innovative screening methods are doubtful to exchange mammography in the close upcoming for screening the overall people.

Keywords: breast cancer, screening, metastasis, methods

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Authors: Mubita Namuyamba

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Despite an increase in the number of cancer programs and partnerships in cancer care provision, the burden of cancer in Zambia is increasingly having a significant impact on morbidity and mortality rates. The increase in cancer morbidity and mortality rates has given rise to psychological and psycho social implications (PPsI) in cancer care. Cancer patients, care givers and health care providers are faced with a multitude of PPsIs in cancer care that mainly impact negatively on the management of cancer patients. The study adopted a case study design and was purposively conducted at the Cancer Diseases Hospital in Lusaka (Zambia) after obtaining ethical clearance from the Ethics committee. The sample for this study included 70 cancer patients, 20 care givers and 5 hospital staff (4 nurses and 1 doctor). Data was collected using interviews guides, focus group discussion guides and questionnaires respectively. The qualitative data was analysed thematically. The various psychological and psychosocial challenges that conspire to deter the provision of effective cancer care nursing and improved methods of minimizing the psychological and psychosocial implications in cancer care are the products of this study.

Keywords: case study, enquiry, psychological and psycho social aspects, Zambia

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Authors: Imran Ali

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General chemotherapy for cancer treatment has many side and toxic effects. A new approach of targeting nano anti-cancer drug is under development stage and only few drugs are available in the market today. The unique features of these drugs are targeted action on cancer cells only without any side effect. Sometimes, these are called magic drugs. The important molecules used for nano anti-cancer drugs are cisplatin, carboplatin, bleomycin, 5-fluorouracil, doxorubicin, dactinomycin, 6-mercaptopurine, paclitaxel, topotecan, vinblastin and etoposide etc. The most commonly used materials for preparing nano particles carriers are dendrimers, polymeric, liposomal, micelles inorganic, organic etc. The proposed lecture will comprise the-of-art of nano drugs in cancer chemo-therapy including preparation, types of drugs, mechanism, future perspectives etc.

Keywords: cancer, nano-anti-cancer drugs, chemo-therapy, mechanism of action, future perspectives

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Authors: Fatimah Alhomaid

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The present study was planned to investigate the role of molecular changes and immunohistochemical in early detection of colon cancer in Saudi patients. Our results were carried out on 48 patients colon cancer. We obtained our data from laboratory in King Khalid university hospital. The specimens were taken (48) patients with colon cancer 34 male and 14 female and 2 control. The average age of varied from 37-85 years. The tumor was diagnosed as I in tow patients (male and female) and grade 2 in 42 patients (29 male and 13 female) while the grade 3 in 4 patients (all males). The specimens were processed for haematoxylin and eosin staining , immunohistochemical technique and flow cytometry analysis. Our study noted that most patients had adenocarcinoma which characterized by presence of signet-ring cells were very clear in advanced patients of adenocarcinoma. Our sections in adenocarcinoma in grade 2 and stage 3 had an increase in signet ring cells,an increase in the acini of glands and an increase in number of lymphocytes which spread to the muscularis layer. With advancing the disease, there were haemorge in blood and increase in lymphocytes and increase number of nuclei in the tubular glands. Our study was carried on 48 patients, immunohistochemical diagnosis (CK20,PCNA,P53) and the analysis of DNA content by flow cytometry technique. Our study indicated that the presence of correlation between the immunohistochemical analysis for P53 and the grades. The reaction of P53 appeared as strong in nucleus in grades &stage 3 and appeared in other sections as dark brown pigment. Our study indicated that the absence of correlation between the immunohistochemical analysis for pcan and the grades. In our sections, there were strong reactions in the more 80% of nuclei in grade 1& stage 2. Our study indicated that the presence of correlation between the immunohistochemical analysis for CK20 and the grades. Our results indicated the presence of positive reaction in cytoplasm varied from weak to moderate in grade 3 & stage 4. Concerning the Flow cytometry technique our results indicated that the presence of correlation between the DNA and different stages of colon cancer.

Keywords: DNA-CK20, PCNA, P53, colon cancer

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Authors: H. Al-Awaisi, M. H. Al-Azri, S. Al-Rasbi, M. Al-Moundhri

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Breast cancer is the most common cancer among females worldwide. It is also the most common cancer among females in Oman with 100 new breast cancer cases diagnosed every year. It has been found that breast cancer have a devastating effect on women’s life. Women diagnosed with breast cancer might develop negative attitudes towards the illness and their bodies. They might also suffer from psychological ailments such as depression. Despite the evidence on the impact of breast cancer diagnosis on women, there was no study found to explore the impact of breast cancer diagnosis among women in Oman. A phenomenological qualitative study was conducted to explore the impact of breast cancer diagnosis on Omani women. Data was collected through semi-structured individual interviews with 11 Omani women diagnosed with breast cancer. Interviews were transcribed verbatim and data were analyzed thematically. From the data, there are four main themes identified in relation to the impact of cancer diagnosis on Omani women. These are 'shock and disbelieve', 'a death sentence', “uncertain future” and “social stigma”. At the time of interviews, all participants had advanced breast cancer with some participants having metastatic disease. The impact of the word “cancer” had a profound and catastrophic effect on the women and their close relatives. In conclusion, breast cancer diagnosis was shocking and mainly perceived as a death sentence by Omani women with uncertain future and social stigma. Regardless of age, maternal status and education level, it is evident that Omani women participated in this study lacked awareness about breast cancer diagnosis, treatment and prognosis.

Keywords: breast cancer, coping, diagnosis, Oman, women

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Authors: Nikhil Agrawal, Adam A. Skelton

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Alzheimer’s disease (AD) is one of the most common forms of dementia, which is caused by misfolding and aggregation of amyloid beta (Aβ) peptides into amyloid-β fibrils (Aβ fibrils). To disrupt the remodeling of Aβ fibrils, a number of candidate molecules have been proposed. To study the molecular mechanisms of Aβ fibrils remodeling we performed a series of all-atom molecular dynamics simulations, a total time of 3µs, in explicit solvent. Several previously undiscovered candidate molecule-Aβ fibrils binding modes are unraveled; one of which shows the direct conformational change of the Aβ fibril by understanding the physicochemical factors responsible for binding and subsequent remodeling of Aβ fibrils by the candidate molecule, open avenues into structure-based drug design for AD can be opened.

Keywords: alzheimer’s disease, amyloid, MD simulations, misfolded protein

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Authors: Junhong Li, Danni Cheng, Yaxin Luo, Xiaowei Yi, Ke Qiu, Wendu Pang, Minzi Mao, Yufang Rao, Yao Song, Jianjun Ren, Yu Zhao

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Background: The number of multiple cancer patients was increasing, and the impact of prior cancer history on salivary gland cancer patients remains unclear. Methods: Clinical, demographic and pathological information on salivary gland cancer patients were retrospectively collected from the Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2017, and the characteristics and prognosis between patients with a prior cancer and those without prior caner were compared. Univariate and multivariate cox proportional regression models were used for the analysis of prognosis. A risk score model was established to exam the impact of treatment on patients with a prior cancer in different risk groups. Results: A total of 9098 salivary gland cancer patients were identified, and 1635 of them had a prior cancer history. Salivary gland cancer patients with prior cancer had worse survival compared with those without a prior cancer (p<0.001). Patients with a different type of first cancer had a distinct prognosis (p<0.001), and longer latent time was associated with better survival (p=0.006) in the univariate model, although both became nonsignificant in the multivariate model. Salivary gland cancer patients with a prior cancer were divided into low-risk (n= 321), intermediate-risk (n=223), and high-risk (n=62) groups and the results showed that patients at high risk could benefit from surgery, radiation therapy, and chemotherapy, and those at intermediate risk could benefit from surgery. Conclusion: Prior cancer history had an adverse impact on the survival of salivary gland cancer patients, and individualized treatment should be seriously considered for them.

Keywords: prior cancer history, prognosis, salivary gland cancer, SEER

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

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

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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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Authors: Ipsita Biswas, Arnab Sarkar, Ashikur Rahaman, Gopeswar Mukherjee, Subhrangsu Chatterjee, Shamee Bhattacharjee, Deba Prasad Mandal

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One of the major reasons for the high mortality rate of lung cancer is the substantial delays in disease detection at late metastatic stages. It is of utmost importance to understand the detailed molecular signaling and detect the molecular markers that can be used for the early diagnosis of cancer. Several studies explored the emerging roles of long noncoding RNAs (lncRNAs) in various cancers as well as lung cancer. A long non-coding RNA LINC00273 was recently discovered to promote cancer cell migration and invasion, and its positive correlation with the pathological stages of metastasis may prove it to be a potential target for inhibiting cancer cell metastasis. Comparing real-time expression of LINC00273 in various human clinical cancer tissue samples with normal tissue samples revealed significantly higher expression in cancer tissues. This long intergenic noncoding RNA was found to be highly expressed in human liver tumor-initiating cells, human gastric adenocarcinoma AGS cell line, as well as human non-small cell lung cancer A549 cell line. SiRNA and shRNA-induced knockdown of LINC00273 in both in vitro and in vivo nude mice significantly subsided AGS and A549 cancer cell migration and invasion. LINC00273 knockdown also reduced TGF-β induced SNAIL, SLUG, VIMENTIN, ZEB1 expression, and metastasis in A549 cells. Plenty of reports have suggested the role of microRNAs of the miR200 family in reversing epithelial to mesenchymal transition (EMT) by inhibiting ZEB transcription factors. In this study, hsa-miR-200a-3p was predicted via IntaRNA-Freiburg RNA tools to be a potential target of LINC00273 with a negative free binding energy of −8.793 kcal/mol, and this interaction was verified as a confirmed target of LINC00273 by RNA pulldown, real-time PCR and luciferase assay. Mechanistically, LINC00273 accelerated TGF-β induced EMT by sponging hsa-miR-200a-3p which in turn liberated ZEB1 and promoted prometastatic functions in A549 cells in vitro as verified by real-time PCR and western blotting. The similar expression patterns of these EMT regulatory pathway molecules, viz. LINC00273, hsa-miR-200a-3p, ZEB1 and TGF-β, were also detected in various clinical samples like breast cancer tissues, oral cancer tissues, lung cancer tissues, etc. Overall, this LINC00273 mediated EMT regulatory signaling can serve as a potential therapeutic target for the prevention of lung cancer metastasis.

Keywords: epithelial to mesenchymal transition, long noncoding RNA, microRNA, non-small-cell lung carcinoma

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Authors: N. K. Caecar Pratiwi, Yunendah Nur Fuadah, Rita Magdalena, R. D. Atmaja, Sofia Saidah, Ocky Tiaramukti

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Colon cancer or colorectal cancer is a type of cancer that attacks the last part of the human digestive system. Lymphoma and carcinoma are types of cancer that attack human’s colon. Colon cancer causes deaths about half a million people every year. In Indonesia, colon cancer is the third largest cancer case for women and second in men. Unhealthy lifestyles such as minimum consumption of fiber, rarely exercising and lack of awareness for early detection are factors that cause high cases of colon cancer. The aim of this project is to produce a system that can detect and classify images into type of colon cancer lymphoma, carcinoma, or normal. The designed system used 198 data colon cancer tissue pathology, consist of 66 images for Lymphoma cancer, 66 images for carcinoma cancer and 66 for normal / healthy colon condition. This system will classify colon cancer starting from image preprocessing, feature extraction using Principal Component Analysis (PCA) and classification using K-Nearest Neighbor (K-NN) method. Several stages in preprocessing are resize, convert RGB image to grayscale, edge detection and last, histogram equalization. Tests will be done by trying some K-NN input parameter setting. The result of this project is an image processing system that can detect and classify the type of colon cancer with high accuracy and low computation time.

Keywords: carcinoma, colorectal cancer, k-nearest neighbor, lymphoma, principle component analysis

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Authors: S. N. Harun, H. Ahmad

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A series of ruthenium(II) complexes, including two novel compounds [Ru(dppz)2(L)]2+ where dppz = dipyrido-[3,2-a:2’,3’-c]phenazine, and L = 2-phenylimidazo[4,5-f][1,10]phenanthroline (PIP) or 2-(4-hydroxyphenyl)imidazo[4,5-f][1,10]phenanthroline (p-HPIP) have been synthesized and characterized. The previously reported complexes [Ru(bpy)2L]2+ and [Ru(phen)2L]2+ were also prepared. All complexes were characterized by elemental analysis, 1H-NMR spectroscopy, ESI-Mass spectroscopy and FT-IR spectroscopy. The photophysical properties were analyzed by UV-Visible spectroscopy and fluorescence spectroscopy. [Ru(dppz)2(PIP)]2+ and [Ru(dppz)2(p-HPIP)]2+ displayed ‘molecular light-switch’ effect as they have high emission in acetonitrile but no emission in water. The cytotoxicity of all complexes against cancer cell lines Hela and MCF-7 were investigated through standard MTT assay. [Ru(dppz)2(PIP)]2+ showed moderate toxicity on both MCF-7 and Hela with IC50 of 37.64 µM and 28.02 µM, respectively. Interestingly, [Ru(dppz)2(p-HPIP)]2+ exhibited remarkable cytotoxicity results with IC50 of 13.52 µM on Hela and 11.63 µM on MCF-7 cell lines which are comparable to the infamous anti-cancer drug, cisplatin. The cytotoxicity of this complex series increased as the ligands size extended in order of [Ru(bpy)2(L)]2+ < [Ru(phen)2(L)]2+ < [Ru(dppz)2(L)]2+.

Keywords: ruthenium, cytotoxicity, molecular light-switch, anticancer

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Authors: Milica Karadzic, Lidija Jevric, Sanja Podunavac-Kuzmanovic, Strahinja Kovacevic, Sinisa Markov, Aleksandar Okljesa, Andrea Nikolic, Marija Sakac, Katarina Penov Gasi

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This study considered the microbiological activity determination and molecular docking study for selected steroid derivatives of biomedical importance. Minimal inhibitory concentration (MIC) was determined for steroid derivatives against Staphylococcus aureus using macrodilution method. Some of the investigated steroid derivatives express bacteriostatic effect against Staphylococcus aureus. Molecular docking approaches are the most widely used techniques for predicting the binding mode of a ligand. Molecular docking study was done for steroid derivatives for androgen receptor negative prostate cancer cell line (PC-3) toward Human Cytochrome P450 CYP17A1. The molecules that had the smallest experimental IC50 values confirmed their ability to dock into active place using suitable molecular docking procedure. The binding disposition of those molecules was thoroughly investigated. Microbiological analysis and molecular docking study were conducted with aim to additionally characterize selected steroid derivatives for future investigation regarding their biological activity and to estimate the binding-affinities of investigated derivatives. This article is based upon work from COST Action (TD1305), supported by COST (European Cooperation and Science and Technology).

Keywords: binding affinity, minimal inhibitory concentration, molecular docking, pc-3 cell line, staphylococcus aureus, steroids

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Authors: Karl Kingsley

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Many mechanisms are involved in the control of cellular differentiation and growth, which are often dysregulated in many cancers. Many distinct pathways are involved in these mechanisms of control, including deoxyribonuclease (DNA) methyltransferase and histone deacetylase (HDAC) activation that controls both genetic and epigenetic modifications and micro ribonucleic acid (RNA) expression. Less is known about the expression of DNA methyltransferase (DNMT) and HDAC in oral cancers and the effect on microRNA expression. The primary objective of this study was to evaluate the expression of DNMT and HDAC family members in oral cancer and the concomitant expression of cancer-associated microRNAs. Using commercially available oral cancers, including squamous cell carcinoma (SCC)-4, SCC-9, SCC-15, and SCC-25, RNA was extracted and screened for DNMT, HDAC, and microRNA expression using highly-specific primers and quantitative polymerase chain reaction (qPCR). These data revealed low or absent expression of DNMT-1, which is associated with cellular differentiation but increased expression of DNMT-3a and DNMT-3b in all SCC cell lines compared with normal non-cancerous cell controls. In addition, no expression of HDAC1 and HDAC2 expression was found among the normal, non-cancerous cells but was highly expressed in each of the SCC cell lines examined. Differential expression of oncogenic and cancer-associated microRNAs was also observed among the SCC cell lines, including miR-21, miR-133, miR-149, miR-155, miR-365, and miR-720. These findings also appeared to vary according to observed growth rates among these cells. These data may be the first to demonstrate the expression and association between HDAC and DNMT3 family members among oral cancers. In addition, the differential expression of these epigenetic modifiers may be associated with the expression of specific microRNAs in these cancers, which have not previously been observed to the best of the author's knowledge. In addition, some associations and relationships may exist between the expression of these biomarkers and the rates of growth and proliferation, which may suggest that these expression patterns might represent potentially useful biomarkers to determine tumor aggressiveness and other phenotypic behaviors among oral cancers.

Keywords: oral cancer, DNA methyltransferase, histone deacetylase, microRNA

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Authors: Patricia O. Carvalho, Marcia C. F. Messias, Laura Credidio, Carlos A. R. Martinez

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Lipidomic strategy can provide important information regarding cancer pathogenesis mechanisms and could reveal new biomarkers to enable early diagnosis of rectal adenocarcinoma (RAC). This study set out to evaluate lipoperoxidation biomarkers, and lipidomic signature by gas chromatography (GC) and electrospray ionization-qToF-mass spectrometry (ESI-qToF-MS) combined with multivariate data analysis in plasma from 23 RAC patients (early- or advanced-stages cancer) and 18 healthy controls. The most abundant ions identified in the RAC patients were those of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) while those of lisophosphatidylcholine (LPC), identified as LPC (16:1), LPC (18:1) and LPC (18:2), were down-regulated. LPC plasmalogen containing palmitoleic acid (LPC (P-16:1)), with highest VIP score, showed a low tendency in the cancer patients. Malondialdehyde plasma levels were higher in patients with advanced cancer (III/IV stages) than in the early stages groups and the healthy group (p<0.05). No differences in F2-isoprostane levels were observed between these groups. This study shows that the reduction in plasma levels of LPC plasmalogens associated to an increase in MDA levels may indicate increased oxidative stress in these patients and identify the metabolite LPC (P-16:1) as new biomarkers for RAC.

Keywords: biomarkers, lipidomic, plasmalogen, rectal adenocarcinoma

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Authors: Sam Khozama, Ali M. Mayya

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Breast cancer is one of the most common types in women. Early prediction of breast cancer helps physicians detect cancer in its early stages. Big cancer data needs a very powerful tool to analyze and extract predictions. Machine learning and deep learning are two of the most efficient tools for predicting cancer based on textual data. In this study, we developed a fusion model of two machine learning and deep learning models. To obtain the final prediction, Long-Short Term Memory (LSTM) and ensemble learning with hyper parameters optimization are used, and score-level fusion is used. Experiments are done on the Breast Cancer Surveillance Consortium (BCSC) dataset after balancing and grouping the class categories. Five different training scenarios are used, and the tests show that the designed fusion model improved the performance by 3.3% compared to the individual models.

Keywords: machine learning, deep learning, cancer prediction, breast cancer, LSTM, fusion

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Authors: S. Subramaniam, J. S. A. Rao, P. Ramdas, K. R. Selvaduray, N. M. Han, M. K. Kutty, A. K. Radhakrishnan

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Immune system is a complex system where the immune cells have the capability to respond against a wide range of immune challenges including cancer progression. However, in the event of cancer development, tumour cells trigger immunosuppressive environment via activation of myeloid-derived suppressor cells and T regulatory (Treg) cells. The Treg cells are subset of CD4+ T lymphocytes, known to have crucial roles in regulating immune homeostasis and promoting the establishment and maintenance of peripheral tolerance. Dysregulation of these mechanisms could lead to cancer progression and immune suppression. Recently, there are many studies reporting on the effects of natural bioactive compounds on immune responses against cancer. It was known that tocotrienol-rich-fraction consisting 70% tocotrienols and 30% α-tocopherol is able to exhibit immunomodulatory as well as anti-cancer properties. Hence, this study was designed to evaluate the effects of gamma-tocotrienol (G-T3) supplementation on T-reg cells in a syngeneic mouse model of breast cancer. In this study, female BALB/c mice were divided into two groups and fed with either soy oil (vehicle) or gamma-tocotrienol (G-T3) for two weeks followed by inoculation with tumour cells. All the mice continued to receive the same supplementation until day 49. The results showed a significant reduction in tumour volume and weight in G-T3 fed mice compared to vehicle-fed mice. Lung and liver histology showed reduced evidence of metastasis in tumour-bearing G-T3 fed mice. Besides that, flow cytometry analysis revealed T-helper cell population was increased, and T-regulatory cell population was suppressed following G-T3 supplementation. Moreover, immunohistochemistry analysis showed that there was a marked decrease in the expression of FOXP3 in the G-T3 fed tumour bearing mice. In conclusion, the G-T3 supplementation showed good prognosis towards breast cancer by enhancing the immune response in tumour-bearing mice. Therefore, gamma-T3 can be used as immunotherapy agent for the treatment of breast cancer.

Keywords: breast cancer, gamma tocotrienol, immune suppression, supplement

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Authors: Afaf Alharbi, Qianni Zhang

Abstract:

The identification of malignant tissue in histopathological slides holds significant importance in both clinical settings and pathology research. This paper introduces a methodology aimed at automatically categorizing cancerous tissue through the utilization of a multiple-instance learning framework. This framework is specifically developed to acquire knowledge of the Bernoulli distribution of the bag label probability by employing neural networks. Furthermore, we put forward a neural network based permutation-invariant aggregation operator, equivalent to attention mechanisms, which is applied to the multi-instance learning network. Through empirical evaluation of an openly available colon cancer histopathology dataset, we provide evidence that our approach surpasses various conventional deep learning methods.

Keywords: attention multiple instance learning, MIL and transfer learning, histopathological slides, cancer tissue classification

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Authors: Mohamed Moussaoui, Mouna Baassi, Soukayna Baammi, Hatim Soufi, Mohammed Salah, Rachid Daoud, Achraf EL Allali, Mohammed Elalaoui Belghiti, Said Belaaouad

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The present study aims to investigate the quantitative structure-activity relationship (QSAR) of a series of Thiazole derivatives reported as anticancer agents (hepatocellular carcinoma), using principally the electronic descriptors calculated by the density functional theory (DFT) method and by applying the multiple linear regression method. The developed model showed good statistical parameters (R²= 0.725, R²ₐ𝒹ⱼ= 0.653, MSE = 0.060, R²ₜₑₛₜ= 0.827, Q²𝒸ᵥ = 0.536). The energy of the highest occupied molecular orbital (EHOMO) orbital, electronic energy (TE), shape coefficient (I), number of rotatable bonds (NROT), and index of refraction (n) were revealed to be the main descriptors influencing the anti-cancer activity. Additional Thiazole derivatives were then designed and their activities and pharmacokinetic properties were predicted using the validated QSAR model. These designed molecules underwent evaluation through molecular docking (MD) and molecular dynamic (MD) simulations, with binding affinity calculated using the MMPBSA script according to a 100 ns simulation trajectory. This process aimed to study both their affinity and stability towards Cyclin-Dependent Kinase 2 (CDK2), a target protein for cancer disease treatment. The research concluded by identifying four CDK2 inhibitors - A1, A3, A5, and A6 - displaying satisfactory pharmacokinetic properties. MDs results indicated that the designed compound A5 remained stable in the active center of the CDK2 protein, suggesting its potential as an effective inhibitor for the treatment of hepatocellular carcinoma. The findings of this study could contribute significantly to the development of effective CDK2 inhibitors.

Keywords: QSAR, ADMET, Thiazole, anticancer, molecular docking, molecular dynamic simulations, MMPBSA calculation

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Authors: Wahab Ali, Oyebade K. Oyedotun, Adnan Khashman

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Breast cancer remains a threat to the woman’s world in view of survival rates, it early diagnosis and mortality statistics. So far, research has shown that many survivors of breast cancer cases are in the ones with early diagnosis. Breast cancer is usually categorized into stages which indicates its severity and corresponding survival rates for patients. Investigations show that the farther into the stages before diagnosis the lesser the chance of survival; hence the early diagnosis of breast cancer becomes imperative, and consequently the application of novel technologies to achieving this. Over the year, mammograms have used in the diagnosis of breast cancer, but the inconclusive deductions made from such scans lead to either false negative cases where cancer patients may be left untreated or false positive where unnecessary biopsies are carried out. This paper presents the application of artificial neural networks in the prediction of severity of breast tumour (whether benign or malignant) using mammography reports and other factors that are related to breast cancer.

Keywords: breast cancer, intelligent classification, neural networks, mammography

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Authors: Adjebli Ahmed, Messis Abdelaziz, Ayeche Riad, Tighilet Karim, Talbi Melissa, Smaili Yanis, Lehri Mokrane, Louardiane Mustapha

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Colorectal cancer is one of the most common types of cancer worldwide, and its incidence has been increasing in recent years. Data and fecal samples from colorectal cancer patients were collected at the Amizour Public Hospital's oncology department (Bejaia, Algeria). Microbiological and cohort study were conducted at the Biological Engineering of Cancers laboratory at the Faculty of Medicine of the University of Bejaia. All the data showed that patients aged between 50 and 70 years were the most affected by colorectal cancer, while the age categories of [30-40] and [40-50] were the least affected. Males were more likely to be at risk of contracting colorectal cancer than females. The most common types of colorectal cancer among the studied population were sigmoid cancer, rectal cancer, transverse colon cancer, and ascending colon cancer. The hereditary factor was found to be more dominant than other risk factors. Bacterial identification revealed the presence of certain pathogenic and opportunistic bacterial genera, such as E. coli, K. pneumoniae, Shigella sp, and Streptococcus group D. These results led us to conclude that dysbiosis of the intestinal microbiome is strongly present in colorectal cancer patients at the EPH of Amizour.

Keywords: microbiome, colorectal cancer, risk factors, bacterial identification

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Authors: Ozlem Oral, Seval Kilic, Ozlem Yedier, Serap Dokmeci, Devrim Gozuacik

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Autophagy is a degradation pathway, activating under stress conditions. It digests macromolecules, such as abnormal proteins and long-lived organelles by engulfing them and by subsequent delivery of the cargo to lysosomes. The members of the phospholipid-dependent serine/threonine kinases, involved in many signaling pathways, which are necessary for the regulation of cellular metabolic activation. Previous studies implicate that, serine/threonine kinases have crucial roles in the mechanism of many diseases depend on the activated and/or inactivated signaling pathway. Data indicates, the signaling pathways activated by serine/threonine kinases are also involved in activation of autophagy mechanism. However, the information about the effect of serine/threonine kinases on autophagy mechanism and the roles of these effects in disease formation is limited. In this study, we investigated the effect of activated serine/threonine kinases on autophagic pathway. We performed a commonly used autophagy technique, GFP-LC3 dot formation and by using microscopy analyses, we evaluated promotion and/or inhibition of autophagy in serine/threonine kinase-overexpressed fibroblasts as well as cancer cells. In addition, we carried out confocal microscopy analyses and examined autophagic flux by utilizing the differential pH sensitivities of RFP and GFP in mRFP-GFP-LC3 probe. Based on the shRNA-library based screening, we identified autophagy-related proteins affected by serine/threonine kinases. We further studied the involvement of serine/threonine kinases on the molecular mechanism of newly identified autophagy proteins and found that, autophagic pathway is indirectly controlled by serine/threonine kinases via specific autophagic proteins. Our data indicate the molecular connection between two critical cellular mechanisms, which have important roles in the formation of many disease pathologies, particularly cancer. This project is supported by TUBITAK-1001-Scientific and Technological Research Projects Funding Program, Project No: 114Z836.

Keywords: autophagy, GFP-LC3 dot formation assay, serine/threonine kinases, shRNA-library screening

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Authors: Begüm Terzi, Özlem Ateş Sönmezoğlu, Ahmet Yildirim

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Drought is the most important factor that limiting the production and productivity of wheat in the world. The yield of wheat, which is one of the most important crop in the world, reduced depend on drought. Researches to minimize effects of drought are one of the most important about breeding of drought resistant varieties. In recent years, benefiting from the drought resistance wild species and rapid advances in molecular biology studies, researches about drought have been accelerated and number of studies were made on molecular plant breeding which included the molecular mechanisms related to drought resistance. The aim of the present study was characterization of some bread wheat lines for drought tolerance which commonly cultivated in different location of Turkey. In this study, registered 9 bread wheat varieties which on the physiological tests about drought tolerance and 10 bread wheat line has been developed by Transitional Zone Agricultural Research Institute were used. SSR, STS, RAPD and SNP markers that associated with drought tolerance were used. The polymorphisms of the markers were determined by screening of two control varieties. For these purpose 40 molecular markers were used and 12 markers of them were polymorphic among the drought tolerance and the drought sensitive varieties. Control varieties were screened using polymorphic markers. All the DNAs on the genotypes will be searched for the presence of QTLs mapped to different chromosomes. Result of the research, the studied genotypes will be grouped according to drought tolerance and will be detected drought tolerance varieties by molecular markers. In addition, the results will be compared also with physiological tests. The drought tolerant wheat genotypes may be used in breeding studies related to drought stress.

Keywords: bread wheat, drought, molecular marker, Triticum aestivum

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Authors: Salina Yahya Saddick

Abstract:

Ovarian cancer remains the most lethal gynecological malignancy due to the lack of highly sensitive and specific screening tools for detection of early-stage disease. The OSE provides the progenitor cells for 90% of human ovarian cancers. Recent morphologic, immunohistochemical and molecular genetic studies have led to the development of a new paradigm for the pathogenesis and origin of epithelial ovarian cancer (EOC) based on a ualistic model of carcinogenesis that divides EOC into two broad categories designated Types I and II which are characterized by specific mutations, including KRAS, BRAF, ERBB2, CTNNB1, PTEN PIK3CA, ARID1A, and PPPR1A, which target specific cell signaling pathways. Type 1 tumors rarely harbor TP53. type I tumors are relatively genetically stable and typically display a variety of somatic sequence mutations that include KRAS, BRAF, PTEN, PIK3CA CTNNB1 (the gene encoding beta catenin), ARID1A and PPP2R1A but very rarely TP53 . The cancer stem cell (CSC) hypothesis postulates that the tumorigenic potential of CSCs is confined to a very small subset of tumor cells and is defined by their ability to self-renew and differentiate leading to the formation of a tumor mass. Potential protein biomarker miRNA, are promising biomarkers as they are remarkably stable to allow isolation and analysis from tissues and from blood in which they can be found as free circulating nucleic acids and in mononuclear cells. Recently, genomic anaylsis have identified biomarkers and potential therapeutic targets for ovarian cancer namely, FGF18 which plays an active role in controlling migration, invasion, and tumorigenicity of ovarian cancer cells through NF-κB activation, which increased the production of oncogenic cytokines and chemokines. This review summarizes update information on epithelial ovarian cancers and point out to the most recent ongoing research.

Keywords: epithelial ovarian cancers, somatic sequence mutations, cancer stem cell (CSC), potential protein, biomarker, genomic analysis, FGF18 biomarker

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Authors: Mohamed Shafi Mahboob Ali

Abstract:

Male breast cancer (MBC) is a rare entity with overall cases reported less than 1%. However, the incidence of MBC is regularly rising every year. Due to the lack of data on MBC, diagnosis and treatment are tailored to female breast cancer. MBC risk increases with age and is usually diagnosed ten years late as the disease progression is slow compared to female breast cancer (FBC). The most common feature of MBC is an intra-ductal variant, and often, upon diagnosis, the stage of the disease is already advanced. The Prognosis of MBC is often flawed, but new treatment modalities are emerging with the current knowledge and advancement. We presented a series of male breast cancer in our center, highlighting the clinicopathological, radiological and treatment options.

Keywords: male, breast, cancer, clinicopathology, ultrasound, CT scan

Procedia PDF Downloads 99