Search results for: breast cancer resistance protein
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 7131

Search results for: breast cancer resistance protein

7011 Investigation of FOXM1 Gene Expression in Breast Cancer and Its Relationship with Mir-216B-5P Expression Level

Authors: Ramin Mehdiabadi, Neda Menbari, Mohammad Nazir Menbari

Abstract:

As a pressing public health concern, breast cancer stands as the predominant oncological diagnosis and principal cause of cancer-related mortality among women globally, accounting for 11.7% of new cancer incidences and 6.9% of cancer-related deaths. The annual figures indicate that approximately 230,480 women are diagnosed with breast cancer in the United States alone, with 39,520 succumbing to the disease. While developed economies have reported a deceleration in both incidence and mortality rates across various forms of cancer, including breast cancer, emerging and low-income economies manifest a contrary escalation, largely attributable to lifestyle-mediated risk factors such as tobacco usage, physical inactivity, and high caloric intake. Breast cancer is distinctly characterized by molecular heterogeneity, manifesting in specific subtypes delineated by biomarkers—Estrogen Receptors (ER), Progesterone Receptors (PR), and Human Epidermal Growth Factor Receptor 2 (HER2). These subtypes, comprising Luminal A, Luminal B, HER2-enriched, triple-negative/basal-like, and normal-like, necessitate nuanced, subtype-specific therapeutic regimens, thereby challenging the applicability of generalized treatment protocols. Within this molecular complexity, the transcription factor Forkhead Box M1 (FoxM1) has garnered attention as a significant driver of cellular proliferation, tumorigenesis, metastatic progression, and treatment resistance in a spectrum of human malignancies, including breast cancer. Concurrently, microRNAs (miRs), specifically miR-216b-5p, have been identified as post-transcriptional gene expression regulators and potential tumor suppressors. The overarching objective of this academic investigation is to explicate the multifaceted interrelationship between FoxM1 and miR-216b-5p across the disparate molecular subtypes of breast cancer. Employing a methodologically rigorous, interdisciplinary research design that incorporates cutting-edge molecular biology techniques, sophisticated bioinformatics analytics, and exhaustive meta-analyses of extant clinical data, this scholarly endeavor aims to unveil novel biomarker-specific therapeutic pathways. By doing so, this research is positioned to make a seminal contribution to the advancement of personalized, efficacious, and minimally toxic treatment paradigms, thus profoundly impacting the global efforts to ameliorate the burden of breast cancer.

Keywords: breast cancer, fox m1, microRNAs, mir-216b-5p, gene expression

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7010 Breast Cancer and BRCA Gene: A Study on Genetic and Environmental Interaction

Authors: Abhishikta Ghosh Roy

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Breast cancer is the most common malignancy among women globally, including India. Human breast cancer results from the genetic and environmental interaction. The present study attempts to understand the molecular heterogeneity of BRCA1 and BRCA2 genes, as well as to understand the association of various lifestyle and reproductive variables for the Breast Cancer risk. The study was conducted amongst 110 patients and 128 controls with total DNA sequencing of flanking and coding regions of BRCA1 BRCA2 genes that revealed ten Single Nucleotide Polymorphisms (SNPs) (6 novels). The controls selected for the study were age, sex and ethnic group matched. After written and informed consent biological samples were collected from the subjects. After detailed molecular analysis, significant (p < 0.005) molecular heterogeneity is revealed in terms of SNPs in BRCA1 (4 Exonic & 1 Intronic) and BRCA2 (2exonic and 3 Intronic) genes. The augmentation study investigated significant (p < 0.05) association with positive family history, early age at menarche, irregular menstrual periods, menopause, prolong contraceptive use, nulliparity, history of abortions, consumption of alcohol and smoking for breast cancer risk. To the best of authors knowledge, this study is the first of its kind, envisaged that the identification of the SNPs and modification of the lifestyle factors might aid to minimize the risk among the Bengalee Hindu females.

Keywords: breast cancer, BRCA, lifestyle, India

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7009 Breast Cancer Diagnosing Based on Online Sequential Extreme Learning Machine Approach

Authors: Musatafa Abbas Abbood Albadr, Masri Ayob, Sabrina Tiun, Fahad Taha Al-Dhief, Mohammad Kamrul Hasan

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Breast Cancer (BC) is considered one of the most frequent reasons of cancer death in women between 40 to 55 ages. The BC is diagnosed by using digital images of the FNA (Fine Needle Aspirate) for both benign and malignant tumors of the breast mass. Therefore, this work proposes the Online Sequential Extreme Learning Machine (OSELM) algorithm for diagnosing BC by using the tumor features of the breast mass. The current work has used the Wisconsin Diagnosis Breast Cancer (WDBC) dataset, which contains 569 samples (i.e., 357 samples for benign class and 212 samples for malignant class). Further, numerous measurements of assessment were used in order to evaluate the proposed OSELM algorithm, such as specificity, precision, F-measure, accuracy, G-mean, MCC, and recall. According to the outcomes of the experiment, the highest performance of the proposed OSELM was accomplished with 97.66% accuracy, 98.39% recall, 95.31% precision, 97.25% specificity, 96.83% F-measure, 95.00% MCC, and 96.84% G-Mean. The proposed OSELM algorithm demonstrates promising results in diagnosing BC. Besides, the performance of the proposed OSELM algorithm was superior to all its comparatives with respect to the rate of classification.

Keywords: breast cancer, machine learning, online sequential extreme learning machine, artificial intelligence

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7008 Application of an Artificial Neural Network to Determine the Risk of Malignant Tumors from the Images Resulting from the Asymmetry of Internal and External Thermograms of the Mammary Glands

Authors: Amdy Moustapha Drame, Ilya V. Germashev, E. A. Markushevskaya

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Among the main problems of medicine is breast cancer, from which a significant number of women around the world are constantly dying. Therefore, the detection of malignant breast tumors is an urgent task. For many years, various technologies for detecting these tumors have been used, in particular, in thermal imaging in order to determine different levels of breast cancer development. These periodic screening methods are a diagnostic tool for women and may have become an alternative to older methods such as mammography. This article proposes a model for the identification of malignant neoplasms of the mammary glands by the asymmetry of internal and external thermal imaging fields.

Keywords: asymmetry, breast cancer, tumors, deep learning, thermogram, convolutional transformation, classification

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7007 The Role of Surgery to Remove the Primary Tumor in Patients with Metastatic Breast Cancer

Authors: A. D. Zikiryahodjaev, L. V. Bolotina, A. S. Sukhotko

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Purpose. To evaluate the expediency and timeliness of performance of surgical treatment as a component of multi-therapy treatment of patients with stage IV breast cancers. Materials and Methods. This investigation comparatively analyzed the results of complex treatment with or without surgery in patients with metastatic breast cancer. We analyzed retrospectively treatment experience of 196 patients with generalized breast cancer in the department of oncology and breast reconstructive surgery of P.A. Herzen Moscow Cancer Research Institute from 2000 to 2012. The average age was (58±1,1) years. Invasive ductul carcinoma was verified in128 patients (65,3%), invasive lobular carcinoma-33 (16,8%), complex form - 19 (9,7%). Complex palliative care involving drug and radiation therapies was performed in two patient groups. The first group includes 124 patients who underwent surgical intervention as complex treatment, the second group includes 72 patients with only medical therapy. Standard systemic therapy was given to all patients. Results. Overall, 3-and 5-year survival in fist group was 43,8 and 21%, in second - 15,1 and 9,3% respectively [p=0,00002 log-rank]. Median survival in patients with surgical treatment composed 32 months, in patients with only systemic therapy-21. The factors having influencing an influence on the prognosis and the quality of life outcomes for of patients with generalized breast cancer were are also studied: hormone-dependent tumor, Her2/neu hyper-expression, reproductive function status (age, menopause existence). Conclusion.Removing primary breast tumor in patients with generalized breast cancer improve long-term outcomes. Three- and five-year survival increased by 28,7 and 16,3% respectively, and median survival–for 11 months. These patients may benefit from resection of the breast tumor. One explanation for the effect of this resection is that reducing the tumor load influences metastatic growth.

Keywords: breast cancer, combination therapy, factors of prognosis, primary tumor

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7006 Prognostic and Predictive Value of Tumor: Infiltrating Lymphocytes in Triple Negative Breast Cancer

Authors: Wooseok Byon, Eunyoung Kim, Junseong Kwon, Byung Joo Song, Chan Heun Park

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Background/Purpose: Previous preclinical and clinical data suggest that increased lymphocytic infiltration would be associated with good prognosis and benefit from immunogenic chemotherapy especially in triple-negative breast cancer (TNBC). We investigated a single-center experience of TNBC and relationship with lymphocytic infiltration. Methods: From January 2004 to December 2012, at the Department of Surgery, Kangbuk Samsung Hospital, Sungkyunkwan University, School of Medicine, we retrospectively reviewed 897 breast cancer patients-clinical outcomes, clinicopathological characteristics, breast cancer subtypes. And we reviewed lymphocytic infiltration of TNBC specimens by two pathologists. Statistical analysis of risk factors associated with recurrence was performed. Results: A total of 897 patients, 76 were TNBC (8.47%). Mean age of TNBC patients were 50.95 (SD10.42) years, mean follow-up periods was 40.06 months. We reviewed 49 slides, and there were 8 recurrent breast cancer patients (16.32%), and 4 patients were expired (8.16%). There were 9 lymphocytic predominant breast cancers (LPBC)-carcinomas with either intratumoral lymphocytes in >60% of tumor cell nests. 1 patient of LPBC was recurred and 8 were not. In multivariate logistic regression, the odds ratio of lymphocytic infiltration was 0.59 (p=0.643). Conclusion: In a single-center experience of TNBC, the lymphocytic infiltration in tumor cell nest might be a good trend on the prognosis but there was not statistically significant.

Keywords: tumor-infiltrating lymphocytes, triple negative breast cancer, medical and health sciences

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7005 Marker-Controlled Level-Set for Segmenting Breast Tumor from Thermal Images

Authors: Swathi Gopakumar, Sruthi Krishna, Shivasubramani Krishnamoorthy

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Contactless, painless and radiation-free thermal imaging technology is one of the preferred screening modalities for detection of breast cancer. However, poor signal to noise ratio and the inexorable need to preserve edges defining cancer cells and normal cells, make the segmentation process difficult and hence unsuitable for computer-aided diagnosis of breast cancer. This paper presents key findings from a research conducted on the appraisal of two promising techniques, for the detection of breast cancer: (I) marker-controlled, Level-set segmentation of anisotropic diffusion filtered preprocessed image versus (II) Segmentation using marker-controlled level-set on a Gaussian-filtered image. Gaussian-filtering processes the image uniformly, whereas anisotropic filtering processes only in specific areas of a thermographic image. The pre-processed (Gaussian-filtered and anisotropic-filtered) images of breast samples were then applied for segmentation. The segmentation of breast starts with initial level-set function. In this study, marker refers to the position of the image to which initial level-set function is applied. The markers are generally placed on the left and right side of the breast, which may vary with the breast size. The proposed method was carried out on images from an online database with samples collected from women of varying breast characteristics. It was observed that the breast was able to be segmented out from the background by adjustment of the markers. From the results, it was observed that as a pre-processing technique, anisotropic filtering with level-set segmentation, preserved the edges more effectively than Gaussian filtering. Segmented image, by application of anisotropic filtering was found to be more suitable for feature extraction, enabling automated computer-aided diagnosis of breast cancer.

Keywords: anisotropic diffusion, breast, Gaussian, level-set, thermograms

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7004 Thermalytix: An Advanced Artificial Intelligence Based Solution for Non-Contact Breast Screening

Authors: S. Sudhakar, Geetha Manjunath, Siva Teja Kakileti, Himanshu Madhu

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Diagnosis of breast cancer at early stages has seen better clinical and survival outcomes. Survival rates in developing countries like India are very low due to accessibility and affordability issues of screening tests such as Mammography. In addition, Mammography is not much effective in younger women with dense breasts. This leaves a gap in current screening methods. Thermalytix is a new technique for detecting breast abnormality in a non-contact, non-invasive way. It is an AI-enabled computer-aided diagnosis solution that automates interpretation of high resolution thermal images and identifies potential malignant lesions. The solution is low cost, easy to use, portable and is effective in all age groups. This paper presents the results of a retrospective comparative analysis of Thermalytix over Mammography and Clinical Breast Examination for breast cancer screening. Thermalytix was found to have better sensitivity than both the tests, with good specificity as well. In addition, Thermalytix identified all malignant patients without palpable lumps.

Keywords: breast cancer screening, radiology, thermalytix, artificial intelligence, thermography

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7003 The Effect of Naringenin on the Apoptosis in T47D Cell Line of Breast Cancer

Authors: AliAkbar Hafezi, Jahanbakhsh Asadi, Majid Shahbazi, Alijan Tabarraei, Nader Mansour Samaei, Hamed Sheibak, Roghaye Gharaei

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Background: Breast cancer is the most common cancer in women. In most cancer cells, apoptosis is blocked. As for the importance of apoptosis in cancer cell death and the role of different genes in its induction or inhibition, the search for compounds that can begin the process of apoptosis in tumor cells is discussed as a new strategy in anticancer drug discovery. The aim of this study was to investigate the effect of Naringenin (NGEN) on the apoptosis in the T47D cell line of breast cancer. Materials and Methods: In this experimental study in vitro, the T47D cell line of breast cancer was selected as a sample. The cells at 24, 48, and 72 hours were treated with doses of 20, 200, and 1000 µm of Naringenin. Then, the transcription levels of the genes involved in apoptosis, including Bcl-2, Bax, Caspase 3, Caspase 8, Caspase 9, P53, PARP-1, and FAS, were assessed using Real Time-PCR. The collected data were analyzed using IBM SPSS Statistics 24.0. Results: The results showed that Naringenin at doses of 20, 200, and 1000 µm in all three times of 24, 48, and 72 hours increased the expression of Caspase 3, P53, PARP-1 and FAS and reduced the expression of Bcl-2 and increased the Bax/Bcl-2 ratio, nevertheless in none of the studied doses and times, had not a significant effect on the expression of Bax, Caspase 8 and Caspase 9. Conclusion: This study indicates that Naringenin can reduce the growth of some cancer cells and cause their deaths through increased apoptosis and decreased anti-apoptotic Bcl-2 gene expression and, resulting in the induction of apoptosis via both internal and external pathways.

Keywords: apoptosis, breast cancer, naringenin, T47D cell line

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7002 Dental Implants in Breast Cancer Patients Receiving Bisphosphonate Therapy

Authors: Mai Ashraf Talaat

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Objectives: The aim of this review article is to assess the success of dental implants in breast cancer patients receiving bisphosphonate therapy and to evaluate the risk of developing bisphosphonate-related osteonecrosis of the jaw following dental implant surgery. Materials and Methods: A thorough search was conducted, with no time or language restriction, using: PubMed, PubMed Central, Web of Science, and ResearchGate electronic databases. Medical Subject Headings (MeSH) terms such as “bisphosphonate”, “dental implant”, “bisphosphonate-related osteonecrosis of the jaw (BRONJ)”, “osteonecrosis”, “breast cancer, MRONJ”, and their related entry terms were used. Eligibility criteria included studies and clinical trials that evaluated the impact of bisphosphonates on dental implants. Conclusion: Breast cancer patients undergoing bisphosphonate therapy may receive dental implants. However, the risk of developing BRONJ and implant failure is high. Risk factors such as the type of BP received, the route of administration, and the length of treatment prior to surgery should be considered. More randomized controlled trials with long-term follow-ups are needed to draw more evidence-based conclusions.

Keywords: dental implants, breast cancer, bisphosphonates, osteonecrosis, bisphosphonate-related osteonecrosis of the jaw

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7001 Delayed Contralateral Prophylactic Mastectomy (CPM): Reasons and Rationale for Patients with Unilateral Breast Cancer

Authors: C. Soh, S. Muktar, C. M. Malata, J. R. Benson

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Introduction Reasons for requesting CPM include prevention of recurrence, peace of mind and moving on after breast cancer. Some women seek CPM as a delayed procedure but factors influencing this are poorly understood. Methods A retrospective analysis examined patients undergoing CPM as either an immediate or delayed procedure with or without breast reconstruction (BR) between January 2009 and December 2019. A cross-sectional survey based on validated questionnaires (5 point Likert scale) explored patients’ decision-making process in terms of timing of CPM and any BR. Results A total of 123 patients with unilateral breast cancer underwent CPM with 39 (32.5%) delayed procedures with or without BR. The response rate amongst patients receiving questionnaires (n=33) was 22/33 (66%). Within this delayed CPM cohort were three reconstructive scenarios 1) unilateral immediate BR with CPM (n=12); 2) delayed CPM with concomitant bilateral BR (n=22); 3) delayed bilateral BR after delayed CPM (n=3). Two patients had delayed CPM without BR. The most common reason for delayed CPM was to complete all cancer treatments (including radiotherapy) before surgery on the unaffected breast (score 2.91). The second reason was unavailability of genetic test results at the time of therapeutic mastectomy (score 2.64) whilst the third most cited reason was a subsequent change in family cancer history. Conclusion Factors for delayed CPM are patient-driven with few women spontaneously changing their mind having initially decided against immediate CPM for reasons also including surgical duration. CPM should be offered as a potentially delayed option with informed discussion of risks and benefits.

Keywords: Breast Cancer, CPM, Prophylactic, Rationale

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7000 Comparison of Breast Surface Doses for Full-Field Digital Mammography and Digital Breast Tomosynthesis Using Breast Phantoms

Authors: Chia-Hui Chen, Chien-Kuo Wang

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Background: Full field digital mammography (FFDM) is widely used in diagnosis of breast cancer. Digital breast tomosynthesis (DBT) has recently been introduced into the clinic and is being used for screening for breast cancer in the general population. Hence, the radiation dose delivered to the patients involved in an imaging protocol is of utmost concern. Aim: To compare the surface radiation dose (ESD) of digital breast tomosynthesis (DBT) and full-field digital mammography (FFDM) by using breast phantoms. Method: We analyzed the average entrance surface dose (ESD) of FFDM and DBT by using breast phantoms. Optically Stimulated luminescent Dosimeters (OSLD) were placed in a tissue-equivalent Breast phantom at difference sites of interest. Absorbed dose measurements were obtained after digital breast tomosynthesis (DBT) and full-field digital mammography (FFDM) exposures. Results: An automatic exposure control (AEC) is proposed for surface dose measurement during DBT and FFDM. The mean ESD values for DBT and FFDM were 6.37 mGy and 3.51mGy, respectively. Using of OSLD measured for surface dose during DBT and FFDM. There were 19.87 mGy and 11.36 mGy, respectively. The surface exposure dose of DBT could possibly be increased by two times with FFDM. Conclusion: The radiation dose from DBT was higher than that of FFDM and the difference in dose between AEC and OSLD measurements at phantom surface.

Keywords: full-field digital mammography, digital breast tomosynthesis, optically stimulated luminescent dosimeters, surface dose

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6999 Impact of Twin Therapeutic Approaches on Certain Biophysiological Parameters among Breast Cancer Patients after Breast Surgery at Selected Hospital

Authors: Selvia Arokiya Mary

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Introduction: Worldwide, breast cancer comprises 10.4% of all cancer incidence among women. In 2004, breast cancer caused 519,000 deaths worldwide (7% of cancer deaths; almost 1% of all deaths). Many women who undergo breast surgery suffer from ill-defined pain syndromes. STATEMENT OF THE PROBLEM: A study to assess the effectiveness of twin therapeutic approaches on certain bio-physiological parameters in breast cancer patients after breast surgery at selected hospital, Chennai. Objectives: This study is to 1. assess the level of certain biophysiological parameters in women after mastectomy. 2. assess the effectiveness of twin therapeutic approaches on certain biophysiological parameters in women after mastectomy. 3. correlate the practice of twin therapeutic approaches with certain biophysiological parameters. 4. associate the selected demographic variables with certain biophysiological parameters in women after mastectomy Research Design and Method: Pre experimental research design was used. Fifty women were selected by using convenient sampling technique at government general hospital, Chennai. Results: The Level of pain shows, in the study group 49(98%) of them had moderate in the pre test and after the intervention all of them had mild pain in the post test. In relation to level of shoulder function before the intervention shows that in the study group 49(98%) of them had movement towards gravity and after intervention 24 (48%) of them had movement against gravity maximum resistance. There was a significant reduction in pain and shoulder stiffness level at a ‘P’ level of < 0.001. There was a negative correlation between the pranayama practice and the level of pain, there was a positive correlation between the arm exercise practice and the level of shoulder function. There was no significant association between demographic and clinical variables with the level of pain and shoulder function in the study. Hypothesis: There is a significant difference in level of pain and shoulder function among women following breast surgery who receive pranayama & arm exercise programme. The pranayama had effect in terms of reduction of pain, arm exercise programme had effect in prevention of arm stiffness among post operative women following breast surgery. Thus the stated hypothesis was accepted. Conclusion: On the basis of the findings of the present study there was Advancing age related to increasing risk of breast cancer, level of pain also the type of surgery was associated with level of pain and shoulder function, There fore it is to be concluded that the study participants may get benefited by practice of pranayama and arm exercise program.

Keywords: biophysiological parameters breast surgery, lumpectomy , mastectomy, radical mastectomy, twin therapeutic approach, pranayama, arm exercise

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6998 Quercetin and INT3 Inhibits Endocrine Therapy Resistance and Epithelial to Mesenchymal Transition in MCF7 Breast Cancer Cells

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

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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

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6997 Early Diagnosis and Treatment of Cancer Using Synthetic Cationic Peptide

Authors: D. J. Kalita

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Cancer is one of the prime causes of early death worldwide. Mutation of the gene involve in DNA repair and damage, like BRCA2 (Breast cancer gene two) genes, can be detected efficiently by PCR-RFLP to early breast cancer diagnosis and adopt the suitable method of treatment. Host Defense Peptide can be used as blueprint for the design and synthesis of novel anticancer drugs to avoid the side effect of conventional chemotherapy and chemo resistance. The change at nucleotide position 392 of a -› c in the cancer sample of dog mammary tumour at BRCA2 (exon 7) gene lead the creation of a new restriction site for SsiI restriction enzyme. This SNP may be a marker for detection of canine mammary tumour. Support vector machine (SVM) algorithm was used to design and predict the anticancer peptide from the mature functional peptide. MTT assay of MCF-7 cell line after 48 hours of post treatment showed an increase in the number of rounded cells when compared with untreated control cells. The ability of the synthesized peptide to induce apoptosis in MCF-7 cells was further investigated by staining the cells with the fluorescent dye Hoechst stain solution, which allows the evaluation of the nuclear morphology. Numerous cells with dense, pyknotic nuclei (the brighter fluorescence) were observed in treated but not in control MCF-7 cells when viewed using an inverted phase-contrast microscope. Thus, PCR-RFLP is one of the attractive approach for early diagnosis, and synthetic cationic peptide can be used for the treatment of canine mammary tumour.

Keywords: cancer, cationic peptide, host defense peptides, Breast cancer genes

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6996 In vitro and vivo Studies for Assessing the Anti-Proliferative, Anti-Migration and Apoptotic Activity of A. squamosa L. Leaves Extract

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

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

Keywords: apoptosis, breast cancer, migration, proliferation

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6995 Recovery through Shattered Life: The Life World of Illness after Being Diagnosed with Breast Cancer in Taiwan

Authors: Min-Tao Hsu

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This study aims to explore the lived experiences of women with breast cancer, including their life world of illness and their adaptation to breast cancer. Breast cancer is not only a potentially lethal disease, but also a disease that may lead to many irreversible changes for female patients. Especially, in a culture where the wholeness is pursuit as an essential value, the sickness and/or broken body bring great challenge of life. Based on holism and symbolic interactionism, this study used interpretive ethnography including in-depth interviews and participant observations to collect the narrative of women with breast cancer concerning their illness experience. In addition, this study used Agar’s hermeneutic cycle to analyze data. The average age of 35 participants was 54.2. A total of 15 patients were within 2 years of onset, 5 patients were within 2-5 years of the treatment observation period, and 15 patients suffered from breast cancer for more than 5 years. The average age of onset was 50.4. Result: The main storyline of the life world of illness is ‘breast cancer is a turning point of life.’ Loss of breast was in terms of ‘no more a woman’ in Taiwanese culture. Two young women, one in her newly wedded and another right before marry, were divorced and cancelled wedding right after being diagnosed. All of them addressed that they have a ‘broken body.’ Single women accounted that they won’t marry for not being humiliated and most of married women said they never show female body in front of her husband or partner even in intimacy encounter. Three common themes were discovered: 1) new self and new identity; 2) new social relationships and new me; 3) new body and new life. The intertwining bodies, illness, selves, suffering, and medical treatments of female patients were observed. More, the recovery, of cause, was happened when new self, relationship, and new body were generated. Their identity to be a woman and a wife is shattered and their life is urged into another facet. For helping them to recovery from such situation, building a new identity and new social fabric on the new body need to be included in nursing care plan.

Keywords: breast cancer, illness narrative, world of illness, self-healing, interpretive ethnography

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6994 Contribution of PALB2 and BLM Mutations to Familial Breast Cancer Risk in BRCA1/2 Negative South African Breast Cancer Patients Detected Using High-Resolution Melting Analysis

Authors: N. C. van der Merwe, J. Oosthuizen, M. F. Makhetha, J. Adams, B. K. Dajee, S-R. Schneider

Abstract:

Women representing high-risk breast cancer families, who tested negative for pathogenic mutations in BRCA1 and BRCA2, are four times more likely to develop breast cancer compared to women in the general population. Sequencing of genes involved in genomic stability and DNA repair led to the identification of novel contributors to familial breast cancer risk. These include BLM and PALB2. Bloom's syndrome is a rare homozygous autosomal recessive chromosomal instability disorder with a high incidence of various types of neoplasia and is associated with breast cancer when in a heterozygous state. PALB2, on the other hand, binds to BRCA2 and together, they partake actively in DNA damage repair. Archived DNA samples of 66 BRCA1/2 negative high-risk breast cancer patients were retrospectively selected based on the presence of an extensive family history of the disease ( > 3 affecteds per family). All coding regions and splice-site boundaries of both genes were screened using High-Resolution Melting Analysis. Samples exhibiting variation were bi-directionally automated Sanger sequenced. The clinical significance of each variant was assessed using various in silico and splice site prediction algorithms. Comprehensive screening identified a total of 11 BLM and 26 PALB2 variants. The variants detected ranged from global to rare and included three novel mutations. Three BLM and two PALB2 likely pathogenic mutations were identified that could account for the disease in these extensive breast cancer families in the absence of BRCA mutations (BLM c.11T > A, p.V4D; BLM c.2603C > T, p.P868L; BLM c.3961G > A, p.V1321I; PALB2 c.421C > T, p.Gln141Ter; PALB2 c.508A > T, p.Arg170Ter). Conclusion: The study confirmed the contribution of pathogenic mutations in BLM and PALB2 to the familial breast cancer burden in South Africa. It explained the presence of the disease in 7.5% of the BRCA1/2 negative families with an extensive family history of breast cancer. Segregation analysis will be performed to confirm the clinical impact of these mutations for each of these families. These results justify the inclusion of both these genes in a comprehensive breast and ovarian next generation sequencing cancer panel and should be screened simultaneously with BRCA1 and BRCA2 as it might explain a significant percentage of familial breast and ovarian cancer in South Africa.

Keywords: Bloom Syndrome, familial breast cancer, PALB2, South Africa

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6993 Psychosocial Determinants of Quality of Life After Treatment for Breast Cancer - A Systematic Review

Authors: Lakmali Anthony, Madeline Gillies

Abstract:

Purpose: Decreasing mortality has led to increased focus on patient-reported outcomes such as quality of life (QoL) in breast cancer. Breast cancer patients often have decreased QoL even after treatment is complete. This systematic review of the literature aims to identify psychosocial factors associated with decreased QoL in post-treatment breast cancer patients. Methodology: This systematic review was performed in accordance with the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations. The search was conducted in MEDLINE, EMBASE, and PsychINFO using MeSH headings. The two authors screened studies for relevance and extracted data. Results: Seventeen studies were identified, including 3,150 total participants (mean = 197) with a mean age of 51.9 years. There was substantial heterogeneity in measures of QoL. The most common was the European Organisation for Research and Treatment of Cancer QLQ-C30 (n=7, 41.1%). Most studies (n=12, 70.5%) found that emotional distress correlated with poor QoL, while 3 found no significant association. The most common measure of emotional distress was the Hospital Anxiety and Depression Scale (n=12, 70.5%). Other psychosocial factors associated with QoL were unmet needs, problematic social support, and negative affect. Clinicopathologic determinants included mastectomy without reconstruction, stage IV disease, and adjuvant chemotherapy. Conclusion: This systematic review provides a summary of the psychosocial determinants of poor QoL in post-treatment breast cancer patients, as well as the most commonly reported measures of these. An understanding of these potentially modifiable determinants of poor outcome is pivotal to the provision of quality, patient-centred care in surgical oncology.

Keywords: breast cancer, quality of life, psychosocial determinants, cancer surgery

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6992 Studying the Anti-Cancer Effects of Thymoquinone on Tumor Cells Through Natural Killer Cells Activity

Authors: Nouf A. Aldarmahi, Nesrin I. Tarbiah, Nuha A. Alkhattabi, Huda F. Alshaibi

Abstract:

Nigella sativa which is known as dark cumin is a well-known example for a widely applicable herbal medicine. Nigella sativa can be effective in a variety of diseases such as hypertension, diabetes, bronchitis, gastrointestinal upset, and cancer. The anticancer effect of Nigella sativa appeared to be mediated by immune-modulatory effect through stimulating human natural killer (NK) cells. This is a type of lymphocytes which is part of the innate immunity, also known as the first line of defense in the body against pathogens. This study investigated the effect of thymoquinone as a major component of Nigella sativa on the molecular cytotoxic pathway of NK cell and the role of thymoquinone therapeutic effect on NK cells. NK cells were cultured with breast tumor cells in different ways and cultured media was collected and the concentration of perforin, granzyme B and interferon-α were measured by ELISA. The cytotoxic effect of NK cells on breast tumor cells was enhanced in the presence of thymoquinone, with increased activity of perforin in NK cells. This improved anticancer effect of thymoquinone on breast cancer cells.

Keywords: breast cancer, cancer cells, natural killer cells, thymoquinone

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6991 Dynamic Contrast-Enhanced Breast MRI Examinations: Clinical Use and Technical Challenges

Authors: Janet Wing-Chong Wai, Alex Chiu-Wing Lee, Hailey Hoi-Ching Tsang, Jeffrey Chiu, Kwok-Wing Tang

Abstract:

Background: Mammography has limited sensitivity and specificity though it is the primary imaging technique for detection of early breast cancer. Ultrasound imaging and contrast-enhanced MRI are useful adjunct tools to mammography. The advantage of breast MRI is high sensitivity for invasive breast cancer. Therefore, indications for and use of breast magnetic resonance imaging have increased over the past decade. Objectives: 1. Cases demonstration on different indications for breast MR imaging. 2. To review of the common artifacts and pitfalls in breast MR imaging. Materials and Methods: This is a retrospective study including all patients underwent dynamic contrast-enhanced breast MRI examination in our centre, performed from Jan 2011 to Dec 2017. The clinical data and radiological images were retrieved from the EPR (electronic patient record), RIS (Radiology Information System) and PACS (Picture Archiving and Communication System). Results and Discussion: Cases including (1) Screening of the contralateral breast in patient with a new breast malignancy (2) Breast augmentation with free injection of unknown foreign materials (3) Finding of axillary adenopathy with an unknown site of primary malignancy (4) Neo-adjuvant chemotherapy: before, during, and after chemotherapy to evaluate treatment response and extent of residual disease prior to operation. Relevant images will be included and illustrated in the presentation. As with other types of MR imaging, there are different artifacts and pitfalls that can potentially limit interpretation of the images. Because of the coils and software specific to breast MR imaging, there are some other technical considerations that are unique to MR imaging of breast regions. Case demonstration images will be available in presentation. Conclusion: Breast MR imaging is a highly sensitive and reasonably specific method for the detection of breast cancer. Adherent to appropriate clinical indications and technical optimization are crucial for achieving satisfactory images for interpretation.

Keywords: MRI, breast, clinical, cancer

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6990 18 F-FDG PET/CT: Utility in Breast Cancer Surgery

Authors: R. Sonda, F. Pellini, A. Invento, S. Mirandola, F. Riolfatti, D. Grigolato, G. P. Pollini

Abstract:

The purpose of study is to assess utility of 18F-FDG PET/CT in patients with breast heteroplasia and possibility of changing the surgery/therapeutic treatment. Among these "under fourty-five" candidated for NAC, the prevalence of change in therapeutic approach in comparison with first and second level exams has been: 43.75%, while by 22% among the "over forty-five". The surgical timing according to first-level exams have been deferred in 31.46% cases; PET/CT has led to a change in therapeutic treatment of 48.31% on the previous given; then the addition of MRI has led to a similar variation. For all the total patients, the prevalent choice was found to the debulking approach by increasing from a prevalence of 12.92% to 15.17%, resulting in a reduction of conservative one.The present study set itself the objective to demonstrate how the FDG PET/CT could improve on breast imaging according to a more appropriate surgery.

Keywords: breast cancer, FGD PET/CT, preoperative staging, surgical approach

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6989 Hyper Tuned RBF SVM: Approach for the Prediction of the Breast Cancer

Authors: Surita Maini, Sanjay Dhanka

Abstract:

Machine learning (ML) involves developing algorithms and statistical models that enable computers to learn and make predictions or decisions based on data without being explicitly programmed. Because of its unlimited abilities ML is gaining popularity in medical sectors; Medical Imaging, Electronic Health Records, Genomic Data Analysis, Wearable Devices, Disease Outbreak Prediction, Disease Diagnosis, etc. In the last few decades, many researchers have tried to diagnose Breast Cancer (BC) using ML, because early detection of any disease can save millions of lives. Working in this direction, the authors have proposed a hybrid ML technique RBF SVM, to predict the BC in earlier the stage. The proposed method is implemented on the Breast Cancer UCI ML dataset with 569 instances and 32 attributes. The authors recorded performance metrics of the proposed model i.e., Accuracy 98.24%, Sensitivity 98.67%, Specificity 97.43%, F1 Score 98.67%, Precision 98.67%, and run time 0.044769 seconds. The proposed method is validated by K-Fold cross-validation.

Keywords: breast cancer, support vector classifier, machine learning, hyper parameter tunning

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6988 Common Regulatory Mechanisms Reveals Links between Aberrant Glycosylation and Biological Hallmarks in Cancer

Authors: Jahanshah Ashkani, Kevin J. Naidoo

Abstract:

Glycosylation is the major posttranslational modification (PTM) process in cellular development. In tumour development, it is marked by structural alteration of carbohydrates (glycans) that is the result of aberrant glycosylation. Altered glycan structures affect cell surface ligand-receptor interactions that interfere with the regulation of cell adhesion, migration, and proliferation. The resulting changes in glycan biosynthesis pathways originate from altered expression of glycosyltransferases and glycosidases. While the alteration in glycosylation patterns is a recognized “hallmark of cancer”, the influential overview of the biology of cancer proposes eight hallmarks with no explicit suggestion to connectivity with glycosylation. Recently, we have discovered a connection between the glycosyltransferase gene expression and cancer type and subtype. Here we present an association between aberrant glycosylation and the biological hallmarks of breast cancer by exploring the common regulatory mechanisms at the genomic scale. The result of this study bridges the glycobiological and biological pathways that are accepted hallmarks of cancer by connecting their common regulatory pathways. This is an impetus for further investigation as target therapies of breast cancer are very likely to be uncovered from this.

Keywords: aberrant glycosylation, biological hallmarks, breast cancer, regulatory mechanism

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6987 Developing an Accurate AI Algorithm for Histopathologic Cancer Detection

Authors: Leah Ning

Abstract:

This paper discusses the development of a machine learning algorithm that accurately detects metastatic breast cancer (cancer has spread elsewhere from its origin part) in selected images that come from pathology scans of lymph node sections. Being able to develop an accurate artificial intelligence (AI) algorithm would help significantly in breast cancer diagnosis since manual examination of lymph node scans is both tedious and oftentimes highly subjective. The usage of AI in the diagnosis process provides a much more straightforward, reliable, and efficient method for medical professionals and would enable faster diagnosis and, therefore, more immediate treatment. The overall approach used was to train a convolution neural network (CNN) based on a set of pathology scan data and use the trained model to binarily classify if a new scan were benign or malignant, outputting a 0 or a 1, respectively. The final model’s prediction accuracy is very high, with 100% for the train set and over 70% for the test set. Being able to have such high accuracy using an AI model is monumental in regard to medical pathology and cancer detection. Having AI as a new tool capable of quick detection will significantly help medical professionals and patients suffering from cancer.

Keywords: breast cancer detection, AI, machine learning, algorithm

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6986 Synergistic Effect of Doxorubicin-Loaded Silver Nanoparticles – Polymeric Conjugates on Breast Cancer Cells

Authors: Nancy M. El-Baz, Laila Ziko, Rania Siam, Wael Mamdouh

Abstract:

Cancer is one of the most devastating diseases, and has over than 10 million new cases annually worldwide. Despite the effectiveness of chemotherapeutic agents, their systemic toxicity and non-selective anticancer actions represent the main obstacles facing cancer curability. Due to the effective enhanced permeability and retention (EPR) effect of nanomaterials, nanoparticles (NPs) have been used as drug nanocarriers providing targeted cancer drug delivery systems. In addition, several inorganic nanoparticles such as silver (AgNPs) nanoparticles demonstrated a potent anticancer activity against different cancers. The present study aimed at formulating core-shell inorganic NPs-based combinatorial therapy based on combining the anticancer activity of AgNPs along with doxorubicin (DOX) and evaluating their cytotoxicity on MCF-7 breast cancer cells. These inorganic NPs-based combinatorial therapies were designed to (i) Target and kill cancer cells with high selectivity, (ii) Have an improved efficacy/toxicity balance, and (iii) Have an enhanced therapeutic index when compared to the original non-modified DOX with much lower dosage The in-vitro cytotoxicity studies demonstrated that the NPs-based combinatorial therapy achieved the same efficacy of non-modified DOX on breast cancer cell line, but with 96% reduced dose. Such reduction in DOX dose revealed that the combination between DOX and NPs possess a synergic anticancer activity against breast cancer. We believe that this is the first report on a synergic anticancer effect at very low dose of DOX against MCF-7 cells. Future studies on NPs-based combinatorial therapy may aid in formulating novel and significantly more effective cancer therapeutics.

Keywords: nanoparticles-based combinatorial therapy, silver nanoparticles, doxorubicin, breast cancer

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6985 Developing a Health Literacy Questionnaire in Breast Cancer

Authors: Lida Moghaddam-Banaem, Mahmood Tavoosi, Soheila Khalili

Abstract:

Objective: The main objective of this study was designing a breast cancer health literacy questionnaire and assess its psychometric properties. Methods: A comprehensive literature review was performed to develop a primary questionnaire consisting of five domains. Qualitative and quantitative content validity were assessed by relevant experts, and after some modifications, the content validity index (CVI) and content validity ratio (CVR) were calculated. Qualitative and quantitative face validity were evaluated by a number of patients, and the impact score for each item was calculated. 225 women with breast cancer were asked to fill out the questionnaire and construct validity was determined by using exploratory factor analysis. The reliability was tested by Cronbach's alpha coefficient. Results: A 36-item questionnaire with five domains of reading, having access, understanding, assessing/judgment, and decision making/behavior was designed. 2 items were omitted in the qualitative content validity process. All items achieved optimum values in CVI, CVR and impact scores. Content and face validity of the questionnaire were confirmed too. According to the exploratory factor analysis, the five-factor solution accounted for 64.98 percent of the observed variance. Conclusion: Due to the obtained satisfactory validity and reliability, this tool can be used to assess health literacy in women with breast cancer. Health policy makers can use these findings for improving health-related behaviors in breast cancer patients.

Keywords: health literacy, breast cancer, questionnaire, psychometric properties

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6984 Microwave Tomography: The Analytical Treatment for Detecting Malignant Tumor Inside Human Body

Authors: Muhammad Hassan Khalil, Xu Jiadong

Abstract:

Early detection through screening is the best tool short of a perfect treatment against the malignant tumor inside the breast of a woman. By detecting cancer in its early stages, it can be recognized and treated before it has the opportunity to spread and change into potentially dangerous. Microwave tomography is a new imaging method based on contrast in dielectric properties of materials. The mathematical theory of microwave tomography involves solving an inverse problem for Maxwell’s equations. In this paper, we present designed antenna for breast cancer detection, which will use in microwave tomography configuration.

Keywords: microwave imaging, inverse scattering, breast cancer, malignant tumor detection

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6983 Role of Mismatch Repair Protein Expression in Colorectal Cancer: A Study from North India

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

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6982 Correlation between Calpain 1 Expression and Proliferating/Apoptotic Index and Prognostic Factors in Triple Negative Breast Cancer

Authors: Shadia Al-Bahlani, Ruqaya Al-Rashdi, Shadia Al-Sinawi, Maya Al-Bahri

Abstract:

Background: Breast cancer is the most common cancer in women worldwide. Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer, which is defined by the absence of Estrogen (ER), Progesterone (PR) and Human epidermal growth factor (Her-2) receptors. The calpain system plays an important role in many cellular processes including apoptosis, necrosis, cell signaling and proliferation. The role of clapins in pathogenesis and tumor progression has been studied in certain cancer types; however, its definite role is not yet established in breast cancer especially in the TNBC subtype. Objectives: This study aims to measure calpain-1 expression and correlate this measurement with the proliferating/apoptotic index as well with the prognostic factors in TNBC patients’ tissue. Materials and Methods: Thirty nine paraffin blocks from patients diagnosed with TNBC were used to measure the expression of calpain-1 and Ki-67 (proliferating marker) proteins using immunohistochemistry. Apoptosis was assessed morphological and biochemically using conventional Haematoxylin and Eosin (H&E) staining method and terminal deoxynucleotidyl transferase-mediate dUTP nick and labeling (TUNEL) assay respectively. Data was statistically analyzed using Pearson X2 test of association. Results: Calpain-1 content was visualized in the nucleus of the TNBC cells and its expression varied from low to high among the patients tissue. Calpain expression showed no significant correlation with the proliferating/apoptotic index as well with the clinicopathological variables. Apoptotic counts quantified by H&E staining showed significant association with the apoptotic TUNEL assay, validating both approaches. Conclusion: Although calpain-1 expression showed no significant association with the clinical outcome, its variable level of expression might indicate a hidden role in breast cancer tissue. Larger number of samples and different mode of assessments are needed to fully investigate such role. Exploring the involvement of calpain-1 in cancer progression might help in considering it as a biomarker of breast cancer.

Keywords: breast cancer, calpain, apoptosis, prognosis

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