Search results for: high-grade serous ovarian cancer

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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Authors: D. Maryama AG. Daud, Zuliana Bacho, Stephanie Chok, DG. Mashitah PG. Baharuddin, Mohd Hatta Tarmizi, Nathira Abdul Majeed, Helen Lasimbang

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Lifestyle, physical activity, food intake, genetics and medication are contributing factors for people getting obese. Which in some of the obese people were a low or non-responder to exercise. And obesity is very common clinical feature in women affected by Polycystic Ovarian Syndrome (PCOS). Labisia pumila var. alata (LP) is a local herb which had been widely used by Malay women in treating menstrual irregularities, painful menstruation and postpartum well-being. Therefore, this study was carried out to investigate the effect of LP with a structured exercise program on anthropometric, body composition and physical fitness performance of PCOS patients. By using a single blind and parallel study design, where by subjects were assigned into a 16-wk structured exercise program (3 times a week) interventions; (LP and exercise; LPE, and exercise only; E). All subjects in the LPE group were prescribed 200mg LP; once a day, for 16 weeks. The training heart rate (HR) was monitored based on a percentage of the maximum HR (HRmax) achieved during submaximal exercise test that was conducted at wk-0 and wk-8. The progression of aerobic exercise intensity from 25–30 min at 60 – 65% HRmax during the first week to 45 min at 75–80% HRmax by the end of this study. Anthropometric (body weight, Wt; waist circumference, WC; and hip circumference, HC), body composition (fat mass, FM; percentage body fat, %BF; Fat Free Mass, FFM) and physical fitness performance (push up to failure, PU; 1-minute Sit Up, SU; and aerobic step test, PVO2max) were measured at wk-0, wk-4, wk-8, wk-12, and wk-16. This study found that LP does not have a significant effect on body composition, anthropometric and physical fitness performance of PCOS patients underwent a structured exercise program. It means LP does not improve exercise responses of PCOS patients towards anthropometric, body composition and physical fitness performance. The overall data shows exercise responses of PCOS patients is by increasing their aerobic endurance and muscle endurance performances, there is a significant reduction in FM, PBF, HC, and Wt significantly. Therefore, exercise program for PCOS patients have to focus on aerobic fitness, and muscle endurance.

Keywords: polycystic ovarian syndrome, Labisia pumila var. alata, body composition, aerobic endurance, muscle endurance, anthropometric

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Authors: Fatemeh Ghaemi, Padideh Feyzi, Zohreh Dortaj

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Cancer is one of the common diseases that may cause death due to malignancy. The physical problems of cancer patients can have an impact on the psychological and social aspects of their lives. Depression is one of these problems that threaten the lives of these patients and can also reduce their quality of life. Helping patients with cancer to find meaning in life can increase their level of health and improve their quality of life. This study thus examines the effectiveness of group logotherapy on the depression and quality of life of women with cancer. Depression was measured using the Beck Depression Inventory (BDI) and quality of life was measured using Quality of Life Questionnaire (WHOQL) with acceptable and reliable indicators in the pre-test and post-test stages. The experimental group received group therapy in eight, sixty-minute sessions and the control group did not receive any intervention. After collecting the questionnaires, the mean and standard deviations were used to describe the data and the statistical method of multivariate analysis of covariance was used at the significant level (P≤0.05). The results were analyzed using SPSS(22). The results showed that there was a significant difference between post-test depression scores in the experimental group and the control group. Also, there was a significant difference between the post-test scores of quality of life and its components (psychological, physical, social and environmental health) in the experimental group and control group. The findings of this study showed the effectiveness of group logotherapy in decreasing depression and improving the quality of life of cancer patients. By focusing the minds of the people on the present and changing the attitude of the human being towards themselves, life and environment can help the depressed people, and by influencing the individual's view of himself, accepting responsibility, accepting life with purpose, paying attention to life uniformly, it allows a person to maintain his quality of life even with cancer. Therefore, it is recommended that this approach be used as a group intervention in hospitals and care units for cancer patients and even in people with certain diseases.

Keywords: cancer, depression, group psychiatry, quality of life

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Authors: Jumanah S. Alawfi

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Polycystic ovary syndrome (PCOS) is a common endocrinopathy among females in their reproductive years. The incidence cases are nearly 1.55 million among females across the globe, with 0.43 million associated disability-adjusted life-years (DALYs). This syndrome is associated with intricate mechanisms typically characterized by insulin resistance (IR), infertility, overweight and/or obesity. Lifestyle interventions are often prescribed as an adjective treatment. Nonetheless, obesity is a complex disease that encompasses multiple dimensions, such as excessive energy intake and genetics. The melanocortin 4 receptor mutation (MC4R) is an important mediator in appetite. There is emerging evidence that suggests its role in the Body Mass Index (BMI) among PCOS subjects, which poses the question of obesity and/or overweight among the PCOS patients who carry the MC4R variants may be caused by overconsumption. Thereby, using other satiety techniques may be beneficial as a part of personalized nutrition. Therefore, the aim of the current mini-review is to discuss the effect of the vegan low glycemic diet on reducing appetite among PCOS patients. The review shows that there is a gap in the knowledge of the effect of the vegan diet on PCOS patients who carry MC4R variants which need further research.

Keywords: polycystic ovarian syndrome (PCOS), Appetite, Melanocortin 4 Receptor Mutation (MC4R)., Obesity

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Authors: Mohsina Akhter

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Cancer has become a wide spread disease around the globe and takes many lives every year. Different treatments are being practiced but all have potential side effects with somewhat less specificity towards target sites. Pseudomonas aeruginosa is known to secrete a protein azurin with special anti-cancer function. It has unique cell penetrating peptide comprising of 18 amino acids that have ability to enter cancer cells specifically. Reported function of Azurin is to stabilize p53 inside the tumor cells and induces apoptosis through Bax mediated cytochrome c release from mitochondria. At laboratory scale, we have made recombinant azurin through cloning rpTZ57R/T-azu vector into E.coli strain DH-5α and subcloning rpET28-azu vector into E.coli BL21-CodonPlus (DE3). High expression was ensured with IPTG induction at different concentrations then optimized high expression level at 1mM concentration of IPTG for 5 hours. Purification has been done by using Ni+2 affinity chromatography. We have concluded that azurin can be a remarkable improvement in cancer therapeutics if it produces on a large scale. Azurin does not enter into the normal cells so it will prove a safe and secure treatment for patients and prevent them from hazardous anomalies.

Keywords: azurin, pseudomonas aeruginosa, cancer, therapeutics

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Authors: S. Tebibel, R. L. Bouchouka, C. Mechati, S. Messaoudi

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The stomach cancer or gastric cancer is an aggressive cancer with a significant geographic disparity. The decrease in frequency is attributed to refrigeration, which has several beneficial consequences, increased consumption of fresh fruits and vegetables, reduced consumption of salt, which was widely used as a food preservative, and less contamination of food by carcinogenic compounds. The infection with Helicobacter pylori is responsible for progressive inflammatory changes in the gastric mucosa usually evolving into stomach cancer in 80% of cases. Methodology: This epidemiological and analytical study concerns 65 patients (46 men and 19 women) with gastric adenocarcinomas with an average age of 56.5 years and a male predominance with a sex ratio of 2.4. Results and Discussion: In this series, the clinical symptoms are dominated by epigastralgia (72.31%), vomiting (27,69%), and slimming (24,62%). The FOGD (Oeso-Gastro Duodenal Fibroscopy) performed in the 65 patients revealed a predominance of the antro-pyloric localization in 19 cases (i.e., 29.23%) and anulcerative budding appearance in 33 subjects (50,77%). Histologically, the moderately differentiated adenocarcinoma is found in 30.77% of patients, followed by well differentiated adenocarcinoma with 26.15% of patients. The immunohistochemical study revealed a positive labeling of half of the T cells by anti-CD3 AC, and a positive labeling of anti-CD20 AC in a diffuse and intense manner, with the presence of CD20-positive lymphoepithelial lesions compatible with CD20 a low grade MALT non-Hodgkin's lymphoma. Conclusion: This framework of analysis revealed some risk factors for gastric cancer, such as food, hygiene, Helicobacter pylori infection, smoking and family history.

Keywords: cancer, Helicobacter pylori, immunohistochemistry, stomach

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Authors: Jean Gray C. Achapero, Mary Margareth P. Ancheta, Patricia Anjelika A. Angeles, Shannon Denzel S. Ao Tai, Carl Brandon C. Barlis, Chrislen Mae B. Benavidez

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Health literacy and awareness of Polycystic ovarian syndrome (PCOS) is a global issue that is under-addressed in the Philippines. Conducting a thorough review of the country's ability to recognize and comprehend the severity of the syndrome should be undertaken, as early treatment is essential to avoid further disorder complications. This research aims to assess the health literacy and awareness of the female residents of Barangay Dagatan, Sabang, and Marauoy Lipa, Batangas on PCOS. It followed a cross-sectional study, and data gathering was done through a pre-assessment using the Single Item Literacy Screener (SILS) and an online population-based survey questionnaire about PCOS awareness. The participants, as based on the objectives and purposive sampling method, were females aged 18-45 years old. Data were analyzed statistically using STATA 13.1 software. The study showed that 339 (76%) out of 444 respondents passed the SILS meaning the residents have proficient health literacy. Among the 339 respondents, 87% (287) had previous knowledge about PCOS. The respondents showed minimal awareness of PCOS symptoms which could be attributed to its broad spectrum of information. Respondents were shown to be most knowledgeable about PCOS physiology, treatment, beliefs, and its remedies. The respondents’ age had no significant association with their health literacy (p=0.31) and PCOS awareness (p=0.60). A significant association was noted, however, in their educational attainment linked with their health literacy (p=<0.0001) and PCOS awareness (p=0.001). It is suggested that reproductive health education even in the lower year levels must be optimized and Local Government Unit (LGU)/Non-Government Organization (NGO)-held seminars should be conducted for knowledge reinforcement. Reliable health information should be more accessible to the public and clinicians must emphasize the importance of the majority of early screening as part of routine physical examination for women of reproductive age to increase health literacy and awareness about PCOS and actively engage in the management of the disease.

Keywords: age, awareness, educational attainment, health literacy, polycystic ovarian syndrome

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Authors: Betzabet García-Mendoza, Rocío Abascal-Mena

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Breast and cervical cancer are among the leading causes of death of women in Mexico. The mortality rate for these diseases is alarming, even though there have been many campaigns for making people self-aware of the importance of conducting gynecological studies for a timely prevention and detection, these have not been enough. This paper presents a mobile application for organizing and controlling gynecological studies in order to help and boost women to take care of their bodies and health. The process of analyzing and designing the mobile application is presented, along with all the steps carried out by following a user-centered design methodology.

Keywords: breast cancer, cervical cancer, gynecological mobile application, paper prototyping, storyboard, women health

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Authors: Taleb L., Benarbia M., Brahmi M., Belmiloud H., Boukerche A.

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Introduction and purpose of the study: Cavum cancer in children and adolescents is rare and represents 8% of all nasopharyngeal cancers treated in our department. Our objective is to study its epidemiological, clinical, therapeutic, and evolutionary particularities. Material and methods: Retrospective study of 39 patients under 20 years old, treated for undifferentiated non-metastatic carcinoma of the nasopharynx at the Emir Abdelkader Cancer Center between 2014 and 2020. Results and statistical analysis: Median age was 14 years [7-19 years], with a sex ratio of 2.9. The median time to diagnosis was 5.6 months [1 to 14 months], the circumstances of the discovery of which were dominated by lymph node syndrome in 43.6% of cases (n=17) followed by a rhinological syndrome in 30.8% of cases (n=13). The tumor stage was T1 for two patients (5.1%), T2 for 8 (20.5%), T3 for 9 (23.1%), T4 for 20 (51.3%), N0 for 2 (5 .1%) N1 for 4 (10.3%), N2 for 28 (71.8%) and N3 for 5 (12.8%). All patients received induction chemotherapy followed by concomitant radiotherapy with cisplatin. The dose of irradiation delivered to the cavum and adenopathies was 66 Gy with fractionation of 2 Gy per session in 69.2% of cases (n=27) and 1.8 Gy in 30.8% of cases (n=12). With a median follow-up of 51 months (15 to 97 months), the locoregional, metastatic, specific, and overall relapse-free survival rates at five years were 91.1%, 73.5%, 66.1%, and 68.4, respectively. Conclusion: Chemotherapy and radiotherapy treatment of cavum cancer in children and adolescents has allowed excellent locoregional control despite the advanced stage of the disease. However, the frequency of metastatic relapses could justify the possible use of systemic maintenance treatment.

Keywords: cancer, nasopharynx, radiotherapy, chemotherapy, survival

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Authors: Saad Al-Shibli, Nasser Amjad, Muna Al Kubaisi, Norra Harun, Shaikh Mizan

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Leptin is a multifunctional hormone produced mainly by adipocyte. Leptin and its receptor have long been found associated with breast cancer. The main aim of this study is to investigate the correlation between Leptin/Leptin receptor and the clinicopathological features of breast cancer. Blood samples for ELISA, tissue samples from tumors and adjacent breast tissue were taken from 51 women with breast cancer with a control group of 40 women with a negative mammogram. Leptin and Leptin receptor in the tissues were estimated by immunohistochemistry (IHC). They were localized at the subcellular level by immunocytochemistry using transmission electron microscopy (TEM). Our results showed significant difference in serum leptin level between control and the patient group, but no difference between pre and post-operative serum leptin levels in the patient group. By IHC, we found that the majority of the breast cancer cells studied, stained positively for leptin and leptin receptors with co-expression of leptin and its receptors. No significant correlation was found between leptin/leptin receptors expression with the race, menopausal status, lymph node metastasis, estrogen receptor expression, progesterone receptor expression, HER2 expression and tumor size. Majority of the patients with distant metastasis were associated with high leptin and leptin receptor expression. TEM views both Leptin and Leptin receptor were found highly concentrated within and around the nucleus of the cancer breast cells, indicating nucleus is their principal seat of actions while the adjacent breast epithelial cells showed that leptin gold particles are scattered all over the cell with much less than that of the cancerous cells. However, presence of high concentration of leptin does not necessarily prove its over-expression, because it could be internalized from outside by leptin receptor in the cells. In contrast, leptin receptor is definitely over-expressed in the ductal breast cancer cells. We conclude that reducing leptin levels, blocking its downstream tissue specific signal transduction, and/or blocking the upstream leptin receptor pathway might help in prevention and therapy of breast cancer.

Keywords: breast cancer, expression, leptin, leptin receptors

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Authors: Fakhrosadat Sajjadian, Ramin Ghasemi Shayan

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The tumor microenvironment plays an fundamental part in tumor start, movement, metastasis, and treatment resistance. It varies from ordinary tissue in terms of its extracellular network, vascular and lymphatic arrange, as well as physiological conditions. The clinical application of atomic cancer imaging is regularly prevented by the tall commercialization costs of focused on imaging operators as well as the constrained clinical applications and little showcase measure of a few operators. . Since numerous cancer types share comparable characteristics of the tumor microenvironment, the capacity to target these biomarkers has the potential to supply clinically translatable atomic imaging advances for numerous types encompassing cancer and broad clinical applications. Noteworthy advance has been made in focusing on the tumor microenvironment for atomic cancer imaging. In this survey, we summarize the standards and methodologies of later progresses in atomic imaging of the tumor microenvironment, utilizing distinctive imaging modalities for early discovery and conclusion of cancer. To conclude, The tumor microenvironment (TME) encompassing tumor cells could be a profoundly energetic and heterogeneous composition of safe cells, fibroblasts, forerunner cells, endothelial cells, flagging atoms and extracellular network (ECM) components.

Keywords: molecular, imaging, TME, medicine

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Authors: Mohd Farooq Naqshbandi

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The four fractions of aqueous extract of Sesame Seeds (Sesamum indicum L.) were studied for invitro DNA fragmentation, cell migration, and cellular apoptosis on SW480 and HTC116 human colorectal cancer cell lines. The seeds of Sesamum indicum were extracted with six solvents, including Methanol, Ethanol, Aqueous, Chloroform, Acetonitrile, and Hexane. The aqueous extract (IC₅₀ value 154 µg/ml) was found to be the most active in terms of cytotoxicity with SW480 human colorectal cancer cell lines. Further fractionation of this aqueous extract on flash chromatography gave four fractions. These four fractions were studied for anticancer and DNA binding studies. Cell viability was assessed by colorimetric assay (MTT). IC₅₀ values for all these four fractions ranged from 137 to 548 µg/mL for the HTC116 cancer cell line and 141 to 402 µg/mL for the SW480 cancer cell line. The four fractions showed good anticancer and DNA binding properties. The DNA binding constants ranged from 10.4 ×10⁴ 5 to 28.7 ×10⁴, showing good interactions with DNA. The DNA binding interactions were due to intercalative and π-π electron forces. The results indicate that aqueous extract fractions of sesame showed inhibition of cell migration of SW480 and HTC116 human colorectal cancer cell lines and induced DNA fragmentation and apoptosis. This was demonstrated by calculating the low wound closure percentage in cells treated with these fractions as compared to the control (80%). Morphological features of nuclei of cells treated with fractions revealed chromatin compression, nuclear shrinkage, and apoptotic body formation, which indicate cell death by apoptosis. The flow cytometer of fraction-treated cells of SW480 and HTC116 human colorectal cancer cell lines revealed death due to apoptosis. The results of the study indicate that aqueous extract of sesame seeds may be used to treat colorectal cancer.

Keywords: Sesamum indicum, cell migration inhibition, apoptosis induction, anticancer activity, colorectal cancer

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Authors: Jacklynn Walters, Amanda A. Alblas, Linda M. Greyling

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Cervical carcinoma is the second most common cancer found in women. Diagnosis of skeletal metastases is uncommon in cervical cancer patients. The aim of this study was to determine the prevalence of skeletal metastases in in a Western Cape skeletal population. Skeletal samples (n=14) from the Kirsten Skeletal Collection at Stellenbosch University, diagnosed pre-mortem with cervical cancer, were examined. Macroscopic analysis was done using low magnification to examine each skeletal element for signs of disease. Skeletons were also x-rayed using the Lodox® Statscan® Imaging system and the scans evaluated by a musculoskeletal radiologist. Three (21%) of the skeletons showed metastases, with the os coxae and lower vertebral column affected in all three cases. Furthermore, metastases occurred in the scapulae and ribs in two of the cases and in one case the skull, mandible, and long bones were affected. Additionally, three skeletons without evidence of skeletal metastases presented with a periosteal reaction on the os coxae in response to the diseased adjacent soft tissue. Previous studies observed that skeletal metastases are more common than what is diagnosed pre-mortem with the vertebral spine most commonly affected. The findings of this study agree with previous reports and illustrate the effectiveness of the Lodox® scanner in diagnoses of metastases in skeletal material.

Keywords: cancer, cervix, radiology, skeletal metastases

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Authors: Aref Aasi, Sahar Ebrahimi Bajgani, Erfan Aasi

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Breast cancer (BC) continues to be the most frequent cancer in females and causes the highest number of cancer-related deaths in women worldwide. Inspired by recent advances in studying the relationship between different patient attributes and features and the disease, in this paper, we have tried to investigate the different classification methods for better diagnosis of BC in the early stages. In this regard, datasets from the University Hospital Centre of Coimbra were chosen, and different machine learning (ML)-based and neural network (NN) classifiers have been studied. For this purpose, we have selected favorable features among the nine provided attributes from the clinical dataset by using a random forest algorithm. This dataset consists of both healthy controls and BC patients, and it was noted that glucose, BMI, resistin, and age have the most importance, respectively. Moreover, we have analyzed these features with various ML-based classifier methods, including Decision Tree (DT), K-Nearest Neighbors (KNN), eXtreme Gradient Boosting (XGBoost), Logistic Regression (LR), Naive Bayes (NB), and Support Vector Machine (SVM) along with NN-based Multi-Layer Perceptron (MLP) classifier. The results revealed that among different techniques, the SVM and MLP classifiers have the most accuracy, with amounts of 96% and 92%, respectively. These results divulged that the adopted procedure could be used effectively for the classification of cancer cells, and also it encourages further experimental investigations with more collected data for other types of cancers.

Keywords: breast cancer, diagnosis, machine learning, biomarker classification, neural network

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Authors: Abdelhadi Adam Salih Denei

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Silver nanoparticles (AgNPs) have been used in cancer therapy, and the area of nanomedicine has made unheard-of strides in recent years. A thorough summary of the development and assessment of AgNPs for their possible use in the fight against cancer is the goal of this review. Targeted delivery methods have been designed to optimise therapeutic efficacy by using AgNPs' distinct physicochemical features, such as their size, shape, and surface chemistry. Firstly, the study provides an overview of the several synthesis routes—both chemical and green—that are used to create AgNPs. Natural extracts and biomolecules are used in green synthesis techniques, which are becoming more and more popular since they are biocompatible and environmentally benign. It is next described how synthesis factors affect the physicochemical properties of AgNPs, emphasising how crucial it is to modify these parameters for particular therapeutic uses. An extensive analysis is conducted on the anticancer potential of AgNPs, emphasising their capacity to trigger apoptosis, impede angiogenesis, and alter cellular signalling pathways. The analysis also investigates the potential benefits of combining AgNPs with currently used cancer treatment techniques, including radiation and chemotherapy. AgNPs' safety profile for use in clinical settings is clarified by a comprehensive evaluation of their cytotoxicity and biocompatibility.

Keywords: silver nanoparticles, cancer, nanocarrier system, targeted delivery

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Authors: Shazia Bano

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Nanoconjugates that integrate photo-based therapeutics and diagnostics within a single platform promise great advances in revolutionizing cancer treatments. However, to achieve high therapeutic efficacy, designing functionally efficacious nanocarriers to tightly retain the drug, promoting selective drug localization and release, and the validation of the efficacy of these nanoconjugates is a great challenge. Here we have designed smart multiagent, liposome based targeted photoactivatable multiagent nanoconjugates, doped with a photoactivatable chromophore benzoporphyrin derivative (BPD) labelled with an active targeting ligand cetuximab to target the EGFR receptor (over expressed in various cancer cells) to deliver a combination of therapeutic agents. This study establishes a tunable nanoplatform for the delivery of the photoactivatable multiagent nanoconjugates for tumor-specific accumulation and targeted destruction of cancer cells in complex cancer model to enhance the therapeutic index of the administrated drugs.

Keywords: targeting, photodynamic therapy, photoactivatable, nanoconjugates

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Authors: Rabah Iratni, Husain El Hasasna, Khawlah Athamneh, Halima Al Sameri, Nehla Benhalilou, Asma Al Rashedi

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Background: Cancer therapies have witnessed great advances in the recent past, however, cancer continues to be a leading cause of death, with colorectal cancer being the fourth cause of cancer-related deaths. Colorectal cancer affects both sexes equally with poor survival rate once it metastasizes. Phytochemicals, which are plant derived compounds, have been on a steady rise as anti-cancer drugs due to the accumulation of evidences that support their potential. Here, we investigated the anticancer effect of Rhus coriaria on colon cancer cells. Material and Method: Human colon cancer HT-29 cell line was used. Protein expression and protein phosphorylation were examined using Western blotting. Transcription activity was measure using Quantitative RT-PCR. Human tumoral clonogenic assay was used to assess cell survival. Senescence was assessed by the senescence-associated beta-galactosidase assay. Results: Rhus coriaria extract (RCE) was found to significantly inhibit the viability and colony growth of human HT-29 colon cancer cells. RCE induced senescence and cell cycle arrest at G1 phase. These changes were concomitant with upregulation of p21, p16, downregulation of cyclin D1, p27, c-myc and expression of Senescence-associated-β-Galactosidase activity. Moreover, RCE induced non-canonical beclin-1independent autophagy and subsequent apoptotic cell death through activation of activation caspase 8 and caspase 7. The blocking of autophagy by 3-methyladenine (3-MA) or chloroquine (CQ) reduced RCE-induced cell death. Further, RCE induced DNA damage, reduced mutant p53 protein level and downregulated phospho-AKT and phospho-mTOR, events that preceded autophagy. Mechanistically, we found that RCE inhibited the AKT and mTOR pathway, a regulator of autophagy, by promoting the proteasome-dependent degradation of both AKT and mTOR proteins. Conclusion: Our findings provide strong evidence that Rhus coriaria possesses strong anti-colon cancer activity through induction of senescence and autophagic cell death, making it a promising alternative or adjunct therapeutic candidate against colon cancer.

Keywords: autophagy, proteasome degradation, senescence, mTOR, apoptosis, Beclin-1

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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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Authors: Jin Boo Jeong

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In this study, we elucidated anti-cancer activity and potential molecular mechanism of DKC against human colorectal cancer cells. DKC-E70 suppressed the proliferation of human colorectal cancer cell lines such as HCT116, SW480, LoVo and HT-29. Although DKC-E70 decreased cyclin D1 expression in protein and mRNA level, decreased level of cyclin D1 protein by DKC-E70 occurred at the earlier time than that of cyclin D1 mRNA, which indicates that DKC-E70-mediated downregulation of cyclin D1 protein may be a consequence of the induction of degradation and transcriptional inhibition of cyclin D1. In cyclin D1 degradation, we found that cyclin D1 downregulation by DKC-E70 was attenuated in presence of MG132. In addition, DKC-E70 phosphorylated threonine-286 (T286) of cyclin D1 and T286A abolished cyclin D1 downregulation by DKC-E70. We also observed that DKC-E70-mediated T286 phosphorylation and subsequent cyclin D1 degradation was blocked in presence of the inhibitors of ERK1/2, p38 or GSK3β. In cyclin D1 transcriptional inhibition, DKC-E70 inhibited the expression of β-catenin and TCF4, and β–catenin/TCF-dependent luciferase activity. Our results suggest that DKC-E70 may downregulate cyclin D1 as one of the potential anti-cancer targets through cyclin D1 degradation by T286 phosphorylation dependent on ERK1/2, p38 or GSK3β, and cyclin D1 transcriptional inhibition through Wnt signaling. From these findings, DKC-E70 has potential to be a candidate for the development of chemoprevention or therapeutic agents for human colorectal cancer. This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2016R1D1A3B03931713).

Keywords: anticancer, calyx of persimmon, cyclin D1, Diospyros kaki Thunb., human colorectal cancer

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Authors: Olivia Rachel Hwang, Yu-Hsuan Joni Shao

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Androgen Deprivation Therapy (ADT) has been a primary treatment for patients with advanced prostate cancer. However, it is associated with numerous adverse effects related to Metabolic Syndrome (MetS), including hypertension, diabetes, hyperlipidaemia, heart diseases and ischemic strokes. However, complications associated with ADT for prostate cancer in Taiwan is not well documented. The purpose of this study is to utilize the data from NHIRD (National Health Insurance Research Database) to examine the trajectory changes of MetS-related complications in men receiving ADT. The risks of developing complications after the treatment were analyzed with multivariate Cox regression model. Covariates including in the model were the complications before the diagnosis of prostate cancer, the age, and the year at cancer diagnosis. A total number of 17268 patients from 1997-2013 were included in this study. The exclusion criteria were patients with any other types of cancer or with the existing MetS-related complications. Changes in MetS-related complications were observed among two treatment groups: 1) ADT (n=9042), and 2) non-ADT (n=8226). The ADT group appeared to have an increased risk in hypertension (hazard ratio 1.08, 95% confidence interval 1.03-1.13, P = 0.001) and hyperlipidemia (hazard ratio 1.09, 95% confidence interval 1.01-1.17, P = 0.02) when compared with non-ADT group in the multivariate Cox regression analyses. In the risk of diabetes, heart diseases, and ischemic strokes, ADT group appeared to have an increased but not significant hazard ratio. In conclusion, ADT was associated with an increased risk in hypertension and hyperlipidemia in prostate cancer patients in Taiwan. The risk of hypertension and hyperlipidemia should be considered while deciding on ADT, especially those with the known history of hypertension and hyperlipidemia.

Keywords: androgen deprivation therapy, ADT, complications, metabolic syndrome, MetS, prostate cancer

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Authors: Dominika Pihikova, Stefan Belicky, Tomas Bertok, Roman Sokol, Petra Kubanikova, Jan Tkac

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Since aberrant glycosylation is frequently accompanied by both physiological and pathological processes in a human body (cancer, AIDS, inflammatory diseases, etc.), the analysis of tumor-associated glycan patterns have a great potential for the development of novel diagnostic approaches. Moreover, altered glycoforms may assist as a suitable tool for the specificity and sensitivity enhancement in early-stage prostate cancer diagnosis. In this paper we discuss the construction and optimization of ultrasensitive sandwich biosensor platform employing lectin as glycan-binding protein. We focus on the immunoassay development, reduction of non-specific interactions and final glycoprofiling of human serum samples including both prostate cancer (PCa) patients and healthy controls. The fabricated biosensor was measured by label-free electrochemical impedance spectroscopy (EIS) with further lectin microarray verification. Furthermore, we analyzed different biosensor interfaces with atomic force microscopy (AFM) in nanomechanical mapping mode showing a significant differences in the altitude. These preliminary results revealing an elevated content of α-2,3 linked sialic acid in PCa patients comparing with healthy controls. All these experiments are important step towards development of point-of-care devices and discovery of novel glyco-biomarkers applicable in cancer diagnosis.

Keywords: biosensor, glycan, lectin, prostate cancer

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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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Authors: Abdullah Saeidi, Aydin Gülses, Christan Flörke

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Skin cancer of the face region is the most common type of malignancy and surgical excision is the preferred approach. However, the clinical long term results reported in the literature are still controversial. Objectives: To describe; 1. Demographical characteristics 2. Affected site, distribution and TNM classification regarding tumor type 3. Surgical aspects • Surgical removal: excision principles, safety margins, the need for secondary resection, primary reconstruction/ defect closure, anesthesia protocol, duration of hospital stay (if any) • Secondary intervention for defect closure/reconstruction: Flap technique, anesthesia protocol, duration of hospital stay (if any), postoperative wound management etc. 4. Tumor recurrences 5. Clinical outcomes 6. Studying the possible therapy approach throw Biostatistical relation and correlation between multiple Histological, diagnostics and clinical Faktors. following surgical ablation of the skin cancer of the head and neck region. Methods: Selection and statistical analysis of medical records of patients who had admitted to the Department of Oral and Maxillofacial Surgery, Universitätsklinikum Schleswig Holstein, Campus Kiel during the period of 2015-2019 will be retrospectively evaluated. Data will be collected via ORBIS Information-Management-System (ORBIS AG, Saarbrücken, Germany).

Keywords: non melanoma skin cancer, face skin cancer, skin reconstruction, non melanoma skin cancer recurrence, non melanoma skin cancer metastases

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Authors: Molnar Catalina, Lexi Frankel, Amalia Ardeljan, Enoch Kim, Marissa Dallara, Omar Rashid

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Introduction: Clostridium difficile (C. diff) is a toxin-producing bacteria that can cause diarrhea and colitis. U.S. Center for Disease Control and Prevention revealed that C. difficile infection (CDI) has increased from 31 cases per 100,000 persons per year in 1996 to 61 per 100,000 in 2003. Approximately 500,000 cases per year occur in the United States. After exposure, the bacteria colonize the colon, where it adheres to the intestinal epithelium where it produces two toxins: TcdA and TcdB. TcdA affects the intestinal epithelium, causing fluid secretion, inflammation, and tissue necrosis, while TcdB acts as a cytotoxin purpose of this study was to evaluate the association between C diff infection and bronchial lung cancer development. Methods: Using ICD- 9 and ICD-10 codes, the data was provided by a Health Insurance Portability and Accountability Act (HIPAA) compliant national database to assess the patients infected with C diff as opposed to the non-infected patients. The Holy Cross Health, Fort Lauderdale, granted access to the database for the purpose of academic research. Patients were matched for age and Charlson Comorbidity Index (CCI). Standard statistical methods were used. Results: Bronchial lung cancer occurrence in the population not infected with C diff infection was 4741, as opposed to the population infected with C. diff, where 2039 cases of lung cancer were observed. The difference was statistically significant (p-value < 2.2x10^e-16), which reveals that C diff might be protective against bronchial lung cancer. The data was then matched by treatment to create to minimize the effect of treatment bias. Bronchial cancer incidence was 422 and 861 in infected vs. non-infected (p-value of < 2.2x10^e-16), which once more indicates that C diff infection could be beneficial in diminishing bronchial cancer development. Conclusion: This retrospective study conveys a statistical correlation between C diff infection and decreased incidence of lung bronchial cancer. Further studies are needed to comprehend the protective mechanisms of C. Diff infection on lung cancer.

Keywords: C. diff, lung cancer, protective, microbiology

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Authors: Nuhi Arslani, Stojan Potrc, Timotej Mikuljan

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Background: In Department of Abdominal and General Surgery of University Medical Centre Maribor, we treated 578 patients for rectal cancer between 2004 and 2014. During and after treatment we especially concentrated on monitoring local and systemic complications. Methods: For analysis, we used data gathered from preoperative diagnostic tests, reports gathered during operation, reports from the pathohistologic review, and reports on complications after surgery and follow up. Results: In the case of 573 (out of 578) patients (99.1%) we performed resection. R0 was achieved in 551 patients (96,1%). R1 was achieved in 8 patients (1,4%). R2 was achieved in 14 patients (2,4%). Local complications were reported in 78 (13.5%) patients and systemic complications were reported in 68 (11.7%). We would like to point out the low number of local and systemic complications. Conclusions: With advances in surgical techniques, with a multimodal-multidisciplinary approach and with the use of total mesorectal excision we experienced a significant improvement in reducing the number of local and systemic complications in patients with rectal cancer. However, there still remains the question for truly optimal care for each patient with rectal cancer and his quality of life after surgical treatment.

Keywords: local complications, rectal cancer, resection, systemic complications

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Authors: Kyung Min Kwom, Young Joo Lee

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Purpose: Up to 90% of pancreatic cancer patient suffer from neuropathic pain. In palliative care setting, pain control in a pancreatic cancer patient is one of the major goals. Ketamine is a NMDA receptor antagonist effective in neuropathic pain. Also, there have been studies about opioid sparing effect of ketamine. This study was held in palliative care unit among pancreatic cancer patients to find out the factors related to ketamine use and the opioid sparing effect. Methods: Medical records of pancreatic cancer patients admitted to St. Mary’s hospital palliative care unit from 2013.1 to 2014.12 were reviewed. Patients were divided into two categories according to ketamine use. Also, opioid use before and after ketamine use was compared in ketamine group. Results: Compared to non ketamine use group, patients in ketamine group required a higher dose of opioid. Total opioid dose, daily opioid dose, number of daily rescue medication, daily average rescue dose were statistically significantly higher in ketamine group. Opioid requirement was increased after ketamine administration. Conclusion: In this study, ketamine group required more opioid. Ketamine is frequently considered in patients with severe pain, requiring high amount of opioid. Also, ketamine did not have an opioid sparing effect. Future studies about palliative use of ketamine in a larger number of patients are required.

Keywords: ketamine, opioid sparing, palliative care, pancreatic cancer

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Authors: Dipanshu Sur, Ratnabali Chakravorty, Rimi Pal, Siddhartha Chatterjee, Joyshree Chaterjee, Amal Mallik

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Background: Polycystic ovary syndrome (PCOS) is a common endocrine disease in reproductive women with a complex hormonal disturbance that affects the menstrual cycle and leads to metabolic consequences in later life. Hyperandrogenaemia is noticeable features of PCOS and influence the process of folliculogenesis in women. The levels of Antimüllerian Hormone (AMH) reflect the number of pre-antral follicles and thus are a marker of oocyte pool – germinal reserve of the ovary for reproduction. Besides its utilization in IVF (In-vitro fertilization), determination of AMH may serve as an additional marker in the diagnostics of PCOS, where increased AMH levels reflect the severity of the disease. The positive correlation of serum AMH with the number of antral follicles was found also in patients with PCOS. Objective: The objective of this study was to investigate the relationship between AMH androgens and whether AMH contributes to altered folliculogenesis in non-obese women with PCOS. Methods: We designed a prospective study which included a total of 65 IVF individuals. It enrolled 26 cases of PCOS based on 2003 Rotterdam criteria and 39 ovulatory normal- non PCOS, healthy, age-matched controls. AMH levels and ovarian morphology were assessed. The relationships between AMH and androgenaemia in patients with and without PCOS were studied. Results: Mean age of PCOS patients were slightly higher than controls (32±4 and 28±3 years, respectively). AMH generally increased with antral follicle count (AFC) [P=0.001], testosterone, and luteinising hormone, and decreased with age, and serum sex hormone binding globulin (SHBG). No significant relationships were found between circulating AMH levels and BMI between PCOS and non-PCOS patients. The calculation of AMH production per antral follicle (AMH/AF) showed that there was a significant difference in median AMH/AF between PCOS and non-PCOS (P =0.001). Both PCOS and non-PCOS groups showed a very similar increase in AMH with increases in AFC, but the PCOS patients had consistently higher AMH across all AFC levels. Conclusions: These observations indicate that there is a connection between AMH and androgens levels between PCOS and non-PCOS East Indian women. Excessive granulosa cell activity may be implicated in the abnormal follicular dynamic of the syndrome. They are higher in women with PCOS and, on the other hand, very low in women with an ovarian failure.

Keywords: anti-Mullerian hormone, polycystic ovary syndrome, antral follicle count, androgens

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Authors: Vasudha Devi, Arul Amuthan, K. Narayanan, Praveen KS, Venkata Rao J

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Background: Siddha Medicine is one of the Indian traditional medical systems, in which the cancer disease is mentioned as 'putrunoi' which literally means the disease of growth like termite mound. There are number of formulations available for the treatment of cancer disease. Neeradi muthu vallathymezugu (NMV) and thamira kattu chendooram (TKC) are two drugs commonly prescribed by Siddha physicians. These drugs have been clinically reported to be safe and effective when given orally. Though these formulations are in practice for centuries, no efforts have been made to standardize them and explore their anti-cancer potential systematically. Objective: To compare the cytotoxic activity of NMV and TKC with doxorubicin using cancer cell lines. Materials and methods: For this study, ethanol extract of NMV was taken, whereas TKC was used as such. In vitro cytotoxic activity was evaluated by sulphorhodamine (SRB) assay against human hepatic cancer cells (HepG2), human breast cancer cells (MCF-7) and human cervical cancer cells [KeLa]. Doxorubicin was used as the standard. The SRB assay is based on the ability of cellular proteins to bind with sulphorhodamine-B. The number of live cells in drug treated cell lines directly affects the color formation in the assay, which is estimated calorimetrically by measuring the absorbance at 540 nm to calculate the cytotoxicity (inhibitory concentration - IC50 value) of the drug. Results: The IC50values of NMV, TKC and doxorubicin against HepG2 were 3.08 µg/ml, 20.21 µg/ml and 1.21µg/ml respectively. In MCF-7, it was 11.75 µg/ml, 17.67 µg/ml and 2.8µg/ml. In HeLa, the values were 24.76 µg/ml, 73.35 µg/ml and 1.12µg/ml. Conclusions: The study proves the possible anti-cancer potential of these two formulations. Compared to TKC, NMV showed good cytotoxic effect even at low dose. Human hepatic cancer cells responded well even at very low dose, when compared to other cancer cells. Though, cytotoxic potential of these compounds was found to be less compared to doxorubicin, the isolated lead compound may have the potential to be used as an anticancer drug clinically.

Keywords: Neeradi muthu vallathymezugu (Hydnocarpus laurifolia), thamira kattu chendooram, cytotoxicity, in-vitro, Siddha Medicine

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Authors: Philippa Saunders, Claire Fletcher

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INTRODUCTION: Prostate cancer is the most prevalent malignancy affecting Western males. It is initially an androgen-dependent disease: androgens bind to the androgen receptor and drive the expression of genes that promote proliferation and evasion of apoptosis. Despite reduced androgen dependence in advanced prostate cancer, androgen receptor signaling remains a key driver of growth. Androgen deprivation therapy (ADT) is, therefore, a first-line treatment approach and works well initially, but resistance inevitably develops. Abiraterone and Enzalutamide are drugs widely used in ADT and are androgen synthesis and androgen receptor signaling inhibitors, respectively. The shortage of other treatment options means acquired resistance to these drugs is a major clinical problem. MicroRNAs (miRs) are important mediators of post-transcriptional gene regulation and show altered expression in cancer. Several have been linked to the development of resistance to ADT. Manipulation of such miRs may be a pathway to breakthrough treatments for advanced prostate cancer. This study aimed to validate ADT resistance-implicated miRs and their clinically relevant targets. MATERIAL AND METHOD: Small RNA-sequencing of Abiraterone- and Enzalutamide-resistant C42 prostate cancer cells identified subsets of miRs dysregulated as compared to parental cells. Real-Time Quantitative Reverse Transcription PCR (qRT-PCR) was used to validate altered expression of candidate ADT resistance-implicated miRs 195-5p, 497-5p and 29a-5p in ADT-resistant and -responsive prostate cancer cell lines, patient-derived xenografts (PDXs) and primary prostate cancer explants. RESULTS AND DISCUSSION: This study suggests a possible role for miR-497-5p in the development of ADT resistance in prostate cancer. MiR-497-5p expression was increased in ADT-resistant versus ADT-responsive prostate cancer cells. Importantly, miR-497-5p expression was also increased in Enzalutamide-treated, castrated (ADT-mimicking) PDXs versus intact PDXs. MiR-195-5p was also elevated in ADT-resistant versus -responsive prostate cancer cells, while there was a drop in miR-29a-5p expression. Candidate clinically relevant targets of miR-497-5p in prostate cancer were identified by mining AGO-PAR-CLIP-seq data sets and may include AVL9 and FZD6. CONCLUSION: In summary, this study identified microRNAs that are implicated in prostate cancer resistance to androgen deprivation therapy and could represent novel therapeutic targets for advanced disease.

Keywords: microRNA, androgen deprivation therapy, Enzalutamide, abiraterone, patient-derived xenograft

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Authors: Sally Shepherd, Craig Murphy

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Introduction: The uterus or cervix are unusual locations as metastatic sites for cancers. It is further unusual for it to be a site of metastasis, whilst the primary malignancy remains occult. Case Report: A 63-year-old female with three months of altered bowel habits underwent a CT scan of the abdomen and pelvis, revealing a bulky uterus and left ovary, nonspecific colonic thickening, and diffuse peritoneal changes. She underwent colposcopy, which revealed a large endocervical polyp that was excised, revealing strongly hormone-positive metastatic invasive lobular breast cancer. She subsequently underwent a PET scan, which showed moderately diffuse activity in the cervix and left adnexa. Breast examination was unremarkable, and screening mammography, ultrasound, and MRI of the breast did not identify any lesions. Her blood tests revealed a Ca 15-3 of 934, CA-125 of 220, and CEA of 27. She was commenced on letrozole and ribociclib with an improvement in her symptoms. Conclusion: It is rare for occult breast cancer to be established and diagnosed by pelvic imaging and biopsy. Suspicion of uterine or cervical metastasis should be heightened in patients with an active or past history of breast cancer.

Keywords: occult breast cancer, cervical metastasis, invasive lobular carcinoma, metastasis

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