Search results for: gynecological cancers

Authors: Buse Bahitli, Samiye Mete

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The aim of the study was to evaluate the quality of sexual life of women with diagnosed gynecological cancer and receive treatment. The study was a descriptive and cross-sectional type, and it was carried out with 276 women. Information Form and Sexual Quality of Life Scale-Female (SQOL) form was used in the study. The data was evaluated using Mann-Whitney U and Kruskal-Wallis test. In the study, Sexual Quality of Life Scale-Female average score was 68.83 ± 21.17. The %43.1 of women was endometrial cancer, %30.8 was cervical cancer, %24.6 was ovarian cancer, and %1.4 was vulvar cancer. The average time to diagnosis of patients is 41.80 ± 47.64 months. There was no significant difference mean SQOL according to individual/sociodemographic characteristics like age, education. Gynecological cancer-related characteristics like gynaecological cancer type, treatment type, surgery type were found not to affect the mean score of SQOL. However, it was found that the difference was due to the higher SQOL score in the group with a diagnosis time of 25 months and over (X²KW= 6.356, p= 0.046). The reason of significant difference means SQOL according to diagnosis over time might be that women adapted to cancer diagnosis. While women with gynaecologic cancer are evaluating their sexual lives, it is necessary to evaluate them with good evaluation tools.

Keywords: gynecological cancers, sexuality, quality of sexual life, SQOL

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Authors: Hatice Kahyaoglu Sut, Serap Unsar, Seda Kurt

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The aim of this study is to investigate sexual quality of life in women with gynecological cancer. This cross-sectional study was conducted on 37 women with gynecological cancer and 39 control women (in menopausal term) at the Gynecooncology and Menopause Clinics of Trakya University Medical Faculty between January and July 2015. Women who had sexual active and willing to participate in the study filled an information form inquiring socio-demographic characteristics and Sexual Quality of Life Questionnaire-Female (SQLQ-F). Data were analyzed by Mann-Whitney-U test and Kruskal-Wallis test. The average age of the women was 52.7 ± 7.6 (51.2 ± 8.7 in women with gynecological cancer, 54.3 ± 6.0 in controls). The SQOL-F scores in women with gynecologic cancer (60.8 ± 22.4) was lower than controls (63.5 ± 20.7), however, there was no statistically significant difference (p = 0.759). Women with gynecological cancer who had vaginal dryness and pain during sexual intercourse (45.7 ± 21.3) were lower SQOL-F total score than control group (66.0 ± 21.7) (p = 0.014). The SQOL-F scores in women who took chemotherapy treatment (55.7 ± 17.8) were lower than in women who had not chemotherapy treatment (86.8 ± 16.6) (p = 0.005). In conclusion, taking chemotherapy treatment and occurring vaginal dryness and pain complaints during sexual intercourse in women with gynecological cancer reduces sexual quality of life. Therefore, sexual quality of life in women with gynecological cancer should be evaluated, and they should be supported in order to improve their sexual quality of life.

Keywords: gynecological cancer, quality of life, sexuality, women

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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: Khadiza Akter, Tammy Greer, Raegan Bishop

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An in-depth study of the psycho-social effects of gynecological health disparities among immigrant women in the USA is the goal of this integrative review paper. Immigrant women frequently encounter unique obstacles that have severe psycho-social repercussions when it comes to receiving high-quality gynecological treatment. The review investigates the interaction of psychological, sociological, and health factors that affect the psycho-social effects that immigrant women experience in recognition of the significance of addressing these imbalances. The difficulties that immigrant women face in providing high-quality gynecological treatment in the USA are examined in this study. These difficulties are caused by a variety of psychological issues, including acculturation stress and stigma, as well as by social problems like prejudice, language hurdles, and cultural norms. Additionally, variations in healthcare access and affordability have a role. This study highlights the particular challenges that immigrant women have in receiving high-quality gynecological treatment in the United States. These difficulties are caused by both social problems like language obstacles, cultural norms, and biases, as well as psychological ones like acculturation stress and stigma. Additionally, variations in gynecological care for immigrant women are greatly influenced by variances in healthcare availability and price. To find pertinent research looking at the psychological effects of gynecological health disparities among immigrant women in the USA, a thorough search of numerous databases was done. Numerous approaches, including mixed, quantitative, and qualitative ones, were used in the studies. The important findings from various investigations were extracted and synthesized after they underwent a careful evaluation. In order to lessen these discrepancies and enhance the overall well-being of immigrant women, healthcare professionals, legislators, and researchers must collaborate to create specialized treatments, regulations, and health system reforms.

Keywords: cultural barriers, gynecological health disparities, health care access, immigrant women, mental health, psycho-social consequences, social stigma

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Authors: Eddy K. Mukadi

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This work is a documentary and descriptive study devoted to the epidemiological, clinical, histopathological and therapeutic profile of breast cancer deals with the department of gynecology and obstetrics of the university clinics of Kinshasa during the period from 1 January 2014 to 31 December 2014. We have identified 56 cases of breast cancer. These cancers accounted for 45.2% of gynecological mammary cancers. The youngest in our series was 18 years old while the oldest was 74 years old; And the mean age of these patients was 43.4 years and mostly multiparous (35.7%). Brides (60.7%) and bachelors (26.8%) were the most affected by breast cancer. The reasons for consultation were dominated by nodules in the breast (48.2%) followed by pain (35.7%) and nipple discharge (14.3%). In 89.2% of the cases, it was the advanced clinical stage (stage 3 and 4) and the infiltrating ductal carcinoma was the most frequent histological type (75%) The malignant tumor was mainly in the left breast (55.3%), and chemotherapy with hormone therapy and patey was the most convenient treatment (42.8%), while patey mastectomy was performed in 12.5% of patients. Because of the high incidence of breast cancer identified in our study, some preventive measures must be taken into account to address this public health problem, including breast autopalpation once a month, Early detection system development of a national breast cancer policy and the implementation of a national breast cancer control program.

Keywords: breast cancer, histopathological profile, epidemiological profile, Kinshasa

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Authors: Amina Aquil, Abdeljalil El Got

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Background: Sleep quality is one of the most important indicators related to the quality of life of patients suffering from cancer. Many factors could affect this quality of sleep and then be considered as associated predictors. Methods: The aim of this study was to assess the prevalence of sleep disorders and the associated factors with impaired sleep quality in Moroccan women with gynecological cancer. A cross-sectional study was carried out within the oncology department of the Ibn Rochd University Hospital, Casablanca, on Moroccan women who had undergone radical surgery for gynecological cancer (n=100). Translated and validated Arabic versions of the following international scales were used: Pittsburgh sleep quality index (PSQI), Hospital Anxiety and Depression Scale (HADS), Rosenberg's self-esteem scale (RSES), and Body image scale (BIS). Results: 78% of participants were considered poor sleepers. Most of the patients exhibited very poor subjective quality, low sleep latency, a short period of sleep, and a low rate of usual sleep efficiency. The vast majority of these patients were in poor shape during the day and did not use sleep medication. Waking up in the middle of the night or early in the morning and getting up to use the bathroom were the main reasons for poor sleep quality. PSQI scores were positively correlated with anxiety, depression, body image dissatisfaction, and lower self-esteem (p < 0.001). Conclusion: Sleep quality and its predictors require a systematic evaluation and adequate management to prevent sleep disturbances and mental distress as well as to improve the quality of life of these patients.

Keywords: body image, gynecological cancer, self esteem, sleep quality

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Authors: Salina Yahya Saddick

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

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

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Authors: Messis A., Adjebli A., Ayeche R., Talbi M., Tighilet K., Louardiane M.

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Cancers are the second cause of death worldwide. Prevalence and incidence of cancers is getting increased by aging and population growth. This study aims to predict and modeling the evolution of breast, Colorectal, Lung, Bladder and Prostate cancers over the period of 2014-2019. In this study, data were analyzed using time series analysis with double exponential smoothing method to forecast the future pattern. To describe and fit the appropriate models, Minitab statistical software version 17 was used. Between 2014 and 2019, the overall trend in the raw number of new cancer cases registered has been increasing over time; the change in observations over time has been increasing. Our forecast model is validated since we have good prediction for the period 2020 and data not available for 2021 and 2022. Time series analysis showed that the double exponential smoothing is an efficient tool to model the future data on the raw number of new cancer cases.

Keywords: cancer, time series, prediction, double exponential smoothing

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Authors: Parvin Samadi Pakchin, Reza Saber, Hossein Ghanbari, Yadollah Omidi

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Ovarian cancer is one of the leading cause of mortality among the gynecological malignancies, and it remains the one of the most prevalent cancer in females worldwide. Tumor markers are biochemical molecules in blood or tissues which can indicates cancers occurrence in the human body. So, the sensitive and specific detection of cancer markers typically recruited for diagnosing and evaluating cancers. Recently extensive research efforts are underway to achieve a simple, inexpensive and accurate device for detection of cancer biomarkers. Compared with conventional immunoassay techniques, electrochemical immunosensors are of great interest, because they are specific, simple, inexpensive, easy to handling and miniaturization. Moreover, in the past decade nanotechnology has played a crucial role in the development of biosensors. In this study, a signal-off electrochemical immunosensor for the detection of CA125 antigen has been developed using chitosan-gold nanoparticles (CS-AuNP) and multi-wall carbon nanotubes (MWCNT) composites. Toluidine blue (TB) is used as redox probe which is immobilized on the electrode surface. CS-AuNP is synthesized by a simple one step method that HAuCl4 is reduced by NH2 groups of chitosan. The CS-AuNP-MWCNT modified electrode has shown excellent electrochemical performance compared with bare Au electrode. MWCNTs and AuNPs increased electrochemical conductivity and accelerate electrons transfer between solution and electrode surface while excessive amine groups on chitosan lead to the effective loading of the biological material (CA125 antibody) and TB on the electrode surface. The electrochemical, immobilization and sensing properties CS-AuNP-MWCNT-TB modified electrodes are characterized by cyclic voltammetry, electrochemical impedance spectroscopy, differential pulse voltammetry and square wave voltammetry with Fe(CN)63−/4−as an electrochemical redox indicator.

Keywords: signal-off electrochemical biosensor, CA125, ovarian cancer, chitosan-gold nanoparticles

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Authors: Buchh Aqsa, Inayat Umar

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Background- Clonidine, α 2 agonist, possesses several properties to make it valuable adjuvant for spinal anesthesia. The study was aimed to evaluate the clinical effects of oral clonidine premedication for laparoscopic gynecological procedures under subarachnoid block. Patients and method- Sixtyfour adult female patients of ASA physical status I and II, aged 25 to 45 years and scheduled for laparoscopic gynecological procedures under the subarachnoid block, were randomized into two comparable equal groups of 32 patients each to received either oral clonidine, 100 µg (Group I) or placebo (Group II), 90 minutes before the procedure. Subarachnoid block was established with of 3.5 ml of 0.5% hyperbaric bupivacaine in all patients. Onset and duration of sensory and motor block, maximum cephalad level, and the regression time to reach S1 sensory level were assessed as primary end points. Sedation, hemodynamic variability, and respiratory depression or any other side effects were evaluated as secondary outcomes. Results- The demographic profile was comparable. The intraoperative hemodynamic parameters showed significant differences between groups. Oral clonidine was accelerated the onset time of sensory and motor blockade and extended the duration of sensory block (216.4 ± 23.3 min versus 165 ± 37.2 min, P <0.05). The duration of motor block showed no significant difference. The sedation score was more than 2 in the clonidine group as compared to the control group. Conclusion- Oral clonidine premedication has extended the duration of sensory analgesia with arousable sedation. It also prevented the post spinal shivering of the subarachnoid block.

Keywords: oral clonidine, subarachnoid block, sensory analgesia, laparoscopic gynaecological

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Authors: Karl Kingsley

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

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

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Authors: Boutheina Ben Abdelmoumen Mardassi, Salim Chibani, Safa Boujemaa, Amaury Vaysse, Julien Guglielmini, Elhem Yacoub

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Background and aim: Mycoplasma hominis (MH) is a pathogenic bacterium belonging to the Mollicutes class. It causes a wide range of gynecological infections and infertility among adults. Recently, we have explored for the first time the phylodistribution of Tunisian M. hominis clinical strains using an expanded MLST. We have demonstrated their distinction into two pure lineages, which each corresponding to a specific pathotype: genital infections and infertility. The aim of this project is to gain further insight into the evolutionary dynamics and the specific genetic factors that distinguish MH pathotypes Methods: Whole genome sequencing of Mycoplasma hominis clinical strains was performed using illumina Miseq. Denovo assembly was performed using a publicly available in-house pipeline. We used prokka to annotate the genomes, panaroo to generate the gene presence matrix and Jolytree to establish the phylogenetic tree. We used treeWAS to identify genetic loci associated with the pathothype of interest from the presence matrix and phylogenetic tree. Results: Our results revealed a clear categorization of the 62 MH clinical strains into two distinct genetic lineages, with each corresponding to a specific pathotype.; gynecological infections and infertility[AV1] . Genome annotation showed that GC content is ranging between 26 and 27%, which is a known characteristic of Mycoplasma genome. Housekeeping genes belonging to the core genome are highly conserved among our strains. TreeWas identified 4 virulence genes associated with the pathotype gynecological infection. encoding for asparagine--tRNA ligase, restriction endonuclease subunit S, Eco47II restriction endonuclease, and transcription regulator XRE (involved in tolerance to oxidative stress). Five genes have been identified that have a statistical association with infertility, tow lipoprotein, one hypothetical protein, a glycosyl transferase involved in capsule synthesis, and pyruvate kinase involved in biofilm formation. All strains harbored an efflux pomp that belongs to the family of multidrug resistance ABC transporter, which confers resistance to a wide range of antibiotics. Indeed many adhesion factors and lipoproteins (p120, p120', p60, p80, Vaa) have been checked and confirmed in our strains with a relatively 99 % to 96 % conserved domain and hypervariable domain that represent 1 to 4 % of the reference sequence extracted from gene bank. Conclusion: In summary, this study led to the identification of specific genetic loci associated with distinct pathotypes in M hominis.

Keywords: mycoplasma hominis, infertility, gynecological infections, virulence genes, antibiotic resistance

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Authors: Stephanie A. Schauder, Gosia Sylwestrzak

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Overweight and obese women report avoiding preventive care due to fear of weight-related bias from medical professionals. Gynecological exams, due to their sensitive and personally invasive nature, are especially susceptible to avoidance. This research investigates the association between body mass index (BMI) and screening rates for breast and cervical cancer using claims data from 1.3 million members of a large health insurance company. Because obesity is associated with increased cancer risk, screenings for these cancers should increase as BMI increases. However, this paper finds that the distribution of cancer screening rates by BMI take an inverted U-shape with underweight and obese members having the lowest screening rates. For cervical cancer screening, those in the target population with a BMI of 23 have the highest screening rate at 68%, while Obese Class III members have a screening rate of 50%. Those in the underweight category have a screening rate of 58%. This relationship persists even after controlling for health and demographic covariates in regression analysis. Interestingly, there is no association between BMI and BRCA (BReast CAncer gene) genetic testing. This is consistent with the narrative that stigma causes avoidance because genetic testing does not involve any assessment of a person’s body. More work must be done to determine how to increase cancer screening rates in those who may feel stigmatized due to their weight.

Keywords: cancer screening, cervical cancer, breast cancer, weight stigma, avoidance of care

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Authors: Shekoufeh Behdad, Amirhossein Yadegari, Leila Ghodrati, Saman Yadegari

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Context: Preoperative anxiety is a common psychological reaction experienced by all patients undergoing surgery. It can have negative effects on the patient's well-being and even impact surgical outcomes. Therefore, finding effective interventions to reduce preoperative anxiety is important in improving patient care. Research Aim: The aim of this study is to compare the effects of oral administration of zaleplon (5 mg) and alprazolam (0.5 mg) on preoperative anxiety levels in women undergoing gynecological abdominal surgery. Methodology: This study is a double-blind, randomized clinical trial conducted after receiving approval from the university's ethics committee and obtaining written informed consent from the patients. The night before the surgery, patients were randomly assigned to receive either 0.5 mg of alprazolam or 5 mg of zaleplon orally. Anxiety levels, measured using a 10-cm visual analog scale, and hemodynamic variables (blood pressure and heart rate) were assessed before drug administration and on the morning of the operation after the patient entered the pre-operation room. Findings: The study found that there were no significant differences in mean anxiety levels or hemodynamic variables before and after administration of either drug in both groups (P value > 0.05). This suggests that both 0.5 mg of alprazolam and 5 mg of zaleplon effectively reduce preoperative anxiety in women undergoing abdominal surgery without serious side effects. Theoretical Importance: This study contributes to the understanding of the effectiveness of alprazolam and zaleplon in reducing preoperative anxiety. It adds to the existing literature on pharmacological interventions for anxiety management, specifically in the context of gynecological abdominal surgery. Data Collection: Data for this study were collected through the assessment of anxiety levels using a visual analog scale and measuring hemodynamic variables, including systolic, diastolic, and mean arterial blood pressures, as well as heart rate. These measurements were taken before drug administration and on the morning of the surgery. Analysis Procedures: Statistical analysis was performed to compare the mean anxiety levels and hemodynamic variables before and after drug administration in the two groups. The significance of the differences was determined using appropriate statistical tests. Questions Addressed: This study aimed to answer the question of whether there are differences in the effects of alprazolam and zaleplon on preoperative anxiety levels in women undergoing gynecological abdominal surgery. Conclusion: The oral administration of both 0.5 mg of alprazolam and 5 mg of zaleplon the night before surgery effectively reduces preoperative anxiety in women undergoing abdominal surgery. These findings have important implications for the management of preoperative anxiety and can contribute to improving the overall surgical experience for patients.

Keywords: zaleplon, alprazolam, premedication, abdominal surgery

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Authors: Aferdita Stroka Koka, Laver Stroka, Juna Musa, Samanda Celaj

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Non-melanoma skin cancers (NMSCs) are the most common human malignancies. About 5.4 million basal and squamous cell skin cancers are diagnosed each year in the US and new cases continue to grow. About eight out of ten of these are basal cell cancers. Squamous cell cancers occur less often. NMSC usually are treatable, but treatment is expensive and can leave scars. In 2019, 167 patients of both sexes suffering from NMSC were treated by traditional medicine. Patients who have been diagnosed with Basal Cell Carcinoma were 122 cases, Squamous Cell Carcinoma 32 cases and both of them 13 cases. Of these,122 cases were ulcerated lesions and 45 unulcerated lesions. All patients were treated with the herbal solution called NILS, which contains extracts of some Albanian plants such as Allium sativum, Jugulans regia and Laurus nobilis. The treatment is done locally, on the surface of the tumor, applying the solution until the tumor mass is destroyed and, after that, giving the necessary time to the wound to make the regeneration that coincides with the complete healing of the wound. We have prepared a collection of photos for each case. Since the first sessions, a shrinkage and reduction of the tumor mass were evident, up to the total disappearance of the lesion at the end of treatment. The normal period of treatment lasted 1 to 2 weeks, depending on the size of the tumor, then take care of it until the closure of the wound, taking the whole process from 1 to 3 months. In 7 patients, the lesion failed to be dominated by treatment and they underwent standard treatment with radiotherapy or surgery, while in 10 patients, the lesion recurred and was treated again. The aim of this survey was to put in evidence the good results obtained by treatment of NMSC with Albanian traditional medicine methods.

Keywords: local treatment, nils, NMSC, traditional medicine

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Authors: Gurbanova J., Majidova N., Ali-Zade S., Hasanova A., Mikailzade P.

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Currently, the problem of oncogynecological diseases is widespread and remains relevant in terms of quantitative growth. It is known that due to the increase in the number of benign diseases of the cervix, the development of precancerous conditions occurs. Benign diseases of the cervix represent the most common gynecological problem, which are often precursors of malignant neoplasms, especially cervical cancer. According to statistics, benign diseases of the cervix cover 25-45% of all gynecological diseases. Among women's oncogynecological diseases, cervical cancer ranks second in the world after breast cancer and ranks first in the mortality rate among oncological diseases in economically underdeveloped countries. We performed a comprehensive clinical and laboratory examination of 130 women aged 18 to 73 with benign cervical diseases. 59 (38.5%) women of reproductive age, as well as 39 (30%) premenopausal and 41 (31.5%) menopausal patients, participated in the study. Detailed anamnesis was collected from all patients, objective and gynecological examination was performed, laboratory and instrumental examinations (USM, IPV DNA, smear microscopy, and PCR bacteriological examination of sexually transmitted infections), simple and extended colposcopy, liquid-based РАР-smear smear and РАР-classic smear examinations were conducted. As a result of the research, the following nosological forms were found in women with benign diseases of the cervix: non-specific vaginitis in 10 (7.7%) cases; ectopia, endocervicitis - 60(46.2%); cervical ectropion - 7(5.4%); cervical polyp - 9(6.9%); cervical leukoplakia - 15(11.5%); atrophic vaginitis - 7(5.4%); condyloma - 12(9.2%); cervical stenosis - 2(1.5%); endometriosis of the cervix - was noted in 8 (6.2%) cases (p<0.001), respectively. Characteristics of the menstrual cycle among the examined women: normal cycle in 97 (74.6%) cases; oligomenorrhea – 23 (17.7%); polymenorrhea – 4(3.1%); algomenorrhea – noted in 6 (4.6%) cases (p<0.001). Cytological examination showed that: the specificity of liquid-based cytology was 76.2%, and the traditional PAP test was set at 70.6%. The overall diagnostic value was calculated to be 86% in liquid-based cytology and 78.5% in conventional PAP tests. Treatment of women with benign diseases of the cervix was carried out by diathermocoagulation method and "FOTEK EA 141M" device. It should be noted that 6 months after the treatment, after treatment with the "FOTEK EA 141M" device, there was no relapse in any patient. Recurrence was found in 23.7% of patients after diathermoelectrocoagulation. Thus, it is clear from the above that the study of cervical pathologies, the determination of optimal examinations, and effective treatment methods is one of the urgent problems facing obstetrics and gynecology.

Keywords: cervical cancer, cytological examination, PAP-smear, non-specific vaginitis

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Authors: Rahul Agarwal, Ashutosh Singh

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Cervical cancer is one of the women related cancers which starts from the pre-cancerous cells and a fraction of women with pre-cancers of the cervix will develop cervical cancer. Cervical pre-cancers if treated in pre-invasive stage can prevent almost all true cervical squamous cell carcinoma. The present study investigates the genes and pathways that are involved in the progression of cervical cancer and are responsible in transition from pre-invasive stage to other advanced invasive stages. The study used GDS3292 microarray data to identify the stage specific genes in cervical cancer and further to generate the network of the significant genes. The microarray data GDS3292 consists of the expression profiling of 10 normal cervices, 7 HSILs and 21 SCCs samples. The study identifies 70 upregulated and 37 downregulated genes in HSIL stage while 95 upregulated and 60 downregulated genes in SCC stages. Biological process including cell communication, signal transduction are highly enriched in both HSIL and SCC stages of cervical cancer. Further, the ppi interaction of genes involved in HSIL and SCC stages helps in identifying the interacting partners. This work may lead to the identification of potential diagnostic biomarker which can be utilized for early stage detection.

Keywords: cervical cancer, HSIL, microarray, SCC

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Authors: Pei-Wen Lin, Ta-I Yang

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Cancer has been one of the leading causes of human death for centuries. Considerable effort has been devoted to developing new treatments to reduce and control cancers. Magnetic particle hyperthermia and near-infrared photothermal therapy are the promising strategies to treat cancers due to its effectiveness with only mild side effects. This study focused on synthesizing magnetic Ag@Fe3O4 nanoparticles applicable for both of magnetic hyperthermia and near-infrared photothermal therapy. The hydrophilic poly(diallyldimethylammonium chloride) polymer was utilized to prepare superparamagnetic Fe3O4 clusters and to promote silver nanoparticles grown on Fe3O4 surfaces, obtaining Ag@Fe3O4 nanoparticles. The morphology (shape and dimension) of Ag nanoparticles was subsequently tailored using commercial LED lights. Therefore, the resulting Ag@Fe3O4 nanoparticles can absorb specific wavelength of light ranging from 400 nm to 800 nm by adjusting the wavelength of LED lights and the free silver ions in reaction solution. Heating performance tests confirmed that the synthesized Ag@Fe3O4 nanoparticles show appreciable heating capability for both of magnetic particle hyperthermia and near-infrared photothermal therapy. The findings in this study could provide new ideas to design functional materials to treat cancers.

Keywords: light-emitting diode assisted synthesis, magnetic particles, photothermal materials, hyperthermia

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Authors: Shakir H. Mohammed Al-Alwany, Saad Hasan M. Ali, Ibrahim Mohammed S. Shnawa

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The study was aimed to define the percentage of detection of high-oncogenic risk types of HPV and their genotyping in archival tissue specimens that ranged from apparently healthy tissue to invasive breast cancer by using one of the recent versions of In Situ Hybridization(ISH) 0.2. To find out rational significance of such genotypes as well as over expressed products of mutants P53 and RB genes on the severity of underlying breast cancers. The DNA of HPV was detected in 46.5 % of tissues from breast cancers while HPV DNA in the tissues from benign breast tumours was detected in 12.5%. No HPV positive–ISH reaction was detected in healthy breast tissues of the control group. HPV DNA of genotypes (16, 18, 31 and 33) was detected in malignant group in frequency of 25.6%, 27.1%, 30.2% and 12.4%, respectively. Over expression of p53 was detected by IHC in 51.2% breast cancer cases and in 50% benign breast tumour group, while none of control group showed P53- over expression. Retinoblastoma protein was detected by IHC test in 49.7% of malignant breast tumours, 54.2% of benign breast tumours but no signal was reported in the tissues of control group. The significance prevalence of expression of mutated p53 & Rb genes as well as detection of high-oncogenic HPV genotypes in patients with breast cancer supports the hypothesis of an etiologic role for the virus in breast cancer development.

Keywords: human papilloma virus, P53, RB, breast cancer

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Authors: Kim Kennedy, Daren Gibson, Stephanie Flukes, Chandra Diwakarla, Lisa Spalding, Leanne Pilkington, Andrew Redfern

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Introduction: Head and neck cancers (HNC) are often associated with the development of non-HNC primaries, as the risk factors that predispose patients to HNC are often risk factors for other cancers. Aim: We sought to evaluate whether there was an increased risk of smoking and alcohol-related cancers and also other cancers in HNC patients and to evaluate whether there is a difference between the rates of non-HNC primaries in Aboriginal compared with non-Aboriginal HNC patients. Methods: We performed a retrospective cohort analysis of 320 HNC patients from a single center in Western Australia, identifying 80 Aboriginal and 240 non-Aboriginal patients matched on a 1:3 ratio by sites, histology, rurality, and age. We collected data on the patient characteristics, tumour features, treatments, outcomes, and past and subsequent HNCs and non-HNC primaries. Results: In the overall study population, there were 86 patients (26.9%) with a metachronous or synchronous non-HNC primary. Non-HNC primaries were actually significantly more common in the non-Aboriginal population compared with the Aboriginal population (30% vs. 17.5%, p=0.02); however, half of these were patients with cutaneous squamous or basal cell carcinomas (cSCC/BCC) only. When cSCC/BCCs were excluded, non-Aboriginal patients had a similar rate as Aboriginal patients (16.7% vs. 15%, p=0.73). There were clearly more cSCC/BCCs in non-Aboriginal patients compared with Aboriginal patients (16.7% vs. 2.5%, p=0.001) and more patients with melanoma (2.5% vs. 0%, p value not significant (p=NS). Rates of most cancers were similar between non-Aboriginal and Aboriginal patients, including prostate (2.9% vs. 3.8%), colorectal (2.9% vs. 2.5%), kidney (1.2% vs. 1.2%), and these rates appeared comparable to Australian Age Standardised Incidence Rates (ASIR) in the general community. Oesophageal cancer occurred at double the rate in Aboriginal patients (3.8%) compared with non-Aboriginal patients (1.7%), which was far in excess of ASIRs which estimated a lifetime risk of 0.59% in the general population. Interestingly lung cancer rates did not appear to be significantly increased in our cohort, with 2.5% of Aboriginal patients and 3.3% of non-Aboriginal patients having lung cancer, which is in line with ASIRs which estimates a lifetime risk of 5% (by age 85yo). Interestingly the rate of Glioma in the non-Aboriginal population was higher than the ASIR, with 0.8% of non-Aboriginal patients developing Glioma, with Australian averages predicting a 0.6% lifetime risk in the general population. As these are small numbers, this finding may well be due to chance. Unsurprisingly, second HNCs occurred at an increased incidence in our cohort, in 12.5% of Aboriginal patients and 11.2% of non-Aboriginal patients, compared to an ASIR of 17 cases per 100,000 persons, estimating a lifetime risk of 1.70%. Conclusions: Overall, 26.9% of patients had a non-HNC primary. When cSCC/BCCs were excluded, Aboriginal and non-Aboriginal patients had similar rates of non-HNC primaries, although non-Aboriginal patients had a significantly higher rate of cSCC/BCCs. Aboriginal patients had double the rate of oesophageal primaries; however, this was not statistically significant, possibly due to small case numbers.

Keywords: head and neck cancer, synchronous and metachronous primaries, other primaries, Aboriginal

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Authors: Waqas Ahmad, Eisha Tahir, Shahper Aqeel, Imran Khalid Niazi, Amjad Iqbal

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Background: Breast conservation surgery applies a number of techniques for accurate localization of lesions. Wire localization remains the method of choice in non-palpable breast cancers post-neoadjuvant chemotherapy. Objective: The aim of our study was to determine the accuracy of wire localization procedures in our department and compare it with internationally set protocols as per the Royal College of Radiologists. Post wire mammography, as well as the margin status of the postoperative specimen, assessed the accuracy of the procedure. Methods: We retrospectively reviewed the data of 225 patients who presented to our department from May 2014 to June 2015 post neoadjuvant chemotherapy with non-palpable cancers. These patients are candidates for wire localized lumpectomies either under ultrasound or stereotactic guidance. Metallic marker was placed in all the patients at the time of biopsy. Post wire mammogram was performed in all the patients and the distance of the wire tip from the marker was calculated. The presence or absence of the metallic clip in the postoperative specimen, as well as the marginal status of the postoperative specimen, was noted. Results: 157 sonographic and 68 stereotactic wire localization procedures were performed. 95% of the wire tips were within 1 cm of the metallic marker. Marginal status was negative in 94% of the patients in histopathological specimen. Conclusion: Our audit report declares more than 95% accuracy of image guided wire localization in successful excision of non-palpable breast lesions.

Keywords: breast, cancer, non-palpable, wire localization

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Authors: Nasrin Hosseinzad, Ramin Ghasemi Shayan

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Chemotherapy is the most common procedure in the treatment of advanced cancers but is justsoberlyoperativeand toxic. Nevertheless, the efficiency of chemotherapy is restrictedowing to multiple drug resistance(MDR). Lately, plentiful preclinical experiments have revealedthatPaclitaxel-Curcumin could be an ultimateapproach to converse MDR and synergistically increase their efficiency. The connotationsamongst B-cell-lymphoma2(BCL-2) and multi-drug-resistance-associated-P-glycoprotein(MDR1) consequence of patients forecast the efficiency of paclitaxel-built chemoradiotherapy. There are evidences of the efficacy of paclitaxel in the treatment of surface-transmission of bladder-cell-carcinoma by manipulating bio-adhesive microspheres accomplishedthroughout measured release of drug at urine epithelium. In Genetically-Modified method, muco-adhesive oily constructionoftricaprylin, Tween 80, and paclitaxel group showed slighter toxicity than control in therapeutic dose. Postoperative chemotherapy-Paclitaxel might be more advantageous for survival than adjuvant chemo-radio-therapy, and coulddiminish postoperative complications in cervical cancer patients underwent a radical hysterectomy.HA-Se-PTX(Hyaluronic acid, Selenium, Paclitaxel) nanoparticles could observablyconstrain the proliferation, transmission, and invasion of metastatic cells and apoptosis. Furthermore, they exhibitedvast in vivo anti-tumor effect. Additionally, HA-Se-PTX displayedminor toxicity on mice-chef-organs. Briefly, HA-Se-PTX mightprogress into a respectednano-scale agentinrespiratory cancers. To sum up, Paclitaxel is considered a profitable anti-cancer drug in the treatment and anti-progress symptoms in malignant cancers.

Keywords: cancer, paclitaxel, chemotherapy, tumor

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Authors: Shreya Sara Ittycheria, K. C. Sivakumar, Shijulal Nelson Sathi, Priya Srinivas

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hCG, a heterodimer composed of α and β subunits, is a peptide hormone having numerous biological functions. Although hCG is expressed by placenta during pregnancy, ectopic β-hCG secretion is observed in many non-trophoblastic tumors including that of breast. In-vitro and in-vivo studies done in the lab, have proved that BRCA1 defective cancers express β-hCG and when β-hCG is expressed or supplemented, it promotes tumor progression and exhibits resistance to carboplatin and ABT888, in such cancers but not in BRCA1 wild type cancers. In cancer cells, instead of binding to its regular receptor, LH-CGR, β-hCG binds with Transforming Growth Factor Receptor 2 (TGFβRII) and phosphorylates it resulting in faster tumor progression through the Smad signaling pathway. Targeting β-hCG could be a potential therapeutic strategy for managing BRCA1 defective cancers. Here, molecular docking and dynamic simulation studies were done to identify potential small molecule inhibitors against β-hCG as there are currently no such inhibitors reported. The binding sites of TGFβRII on β-hCG were identified from the top 10 predicted complexes from Z Dock. Virtual screening of selected commercially available small molecules from various libraries such as ZINC, NCI and Life Chemicals amounting to a total of 50,025 molecules were done. Four potential small molecule inhibitors were identified, RgcbPs-1, RgcbPs-2, RgcbPs-3 and RgcbPs-4 with binding affinities -60.778 kcal/mol, -45.447 kcal/mol, -65.2268 kcal/mol and -82.040 kcal/mol respectively. Further, 100ns Molecular Dynamics (MD) simulation showed that these molecules form stable complexes with β-hCG. RgcbPs-1 maintains hydrogen bonds with Q54, L52, Q46, C100, G36, C57, C38 residues, RgcbPs-2 maintains hydrogen bonds with A83 residue, RgcbPs-3 maintains hydrogen bonds with C57, Y58, R94, G101 residues and RgcbPs-4 maintains hydrogen bonds with G36, C38, T40, C57, D99, C100, G101 and L104 residues of β-hCG all of which coincide with the TGFβRII binding site on β-hCG. These results show that these two inhibitors could be used either singly or in combination for inhibiting β-hCG from binding to TGFβRII and thereby directly inhibiting the tumorigenesis pathway.

Keywords: β-hCG, breast cancer, dynamic simulations, molecular docking, small molecule inhibitors, virtual screening.

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Authors: Khalid Al Saleh, Najlaa AlSayed

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Background: Palliative care is changing from just ‘end of life care’ to care delivered earlier in the disease course. Metanalysis showed that Palliative Performance Scale (PPS) is associated with increased length of survival. The Palliative Care Center (PCC) in Kuwait is the only stand-alone center in Eastern Mediterranean Region with a capacity of 92 beds. We compared clinical characteristics between patients referred from the Specialized Cancer Center and general hospitals in Kuwait to PCC. Method: A cross Sectional survey was conducted since the opening of PCC in January 2011 to June 2013. Patients’ data on demographics, type of the cancer, PPS score and referring hospital were collected and analyzed. Results: Total number of the patients was 142. Mean age was 61.05±14.79 years, 66 patients (47.1%) were males and 74 (52.9%) were females. The most common cancers in males were lung (n=18, 27.3%) followed by head and neck cancers (n=8, 12.1%) and brain tumors (n=7, 10.6%) while in females, the most common cancers were breast cancer (n=12, 16.7%) followed by ovarian cancer (n=10, 13.9%) and Cancer Colon (n=8, 11.1%). Patients with PPS score 30% were 27.9% (n=39), 40% in 40.7% (n=57), and 50% in 17.1% (n=24) respectively. Patients referred from the Specialized Cancer Center had significantly higher portion of patients with PPS score > 30% (73.4%, n=94), compared to patients coming from general hospitals (33.3%, n=4), P value= 0.007. Conclusion: There is significant difference in PPS scores between patients referred from the Specialized Cancer Center compared to patients referred from general hospitals. We encourage that all cancer patients should be treated in Specialized Cancer Centers and earlier involvement of Palliative Care Centers to achieve better survival. Training workshops are needed for health care professionals working in general hospitals to raise awareness about earlier referral of patients to palliative care services.

Keywords: palliative care, kuwait, performance scale differences, pps score, specialized hospitals

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Authors: Abigail Tan, Heng Liang Tan, Vanessa Ding, James Hui, Eng Hin Lee, Andre Choo

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Introduction: Comparative oncology investigates the similarities in spontaneous carcinogenesis between humans and animals, in order to identify treatments that can benefit these patients. Companion animals (CA), like canines and felines, are of special interest when it comes to studying human cancers due to their exposure to the same environmental factors and develop tumours with similar features. The purpose of this study is to explore the cross-reactivity of monoclonal antibodies (mAbs) across cancers in humans and CA. Material and Methods: A panel of CA mAbs generated in the lab was screened on multiple human cancer cell lines through flow cytometry to identify for positive binders. Shortlisted candidates were then characterised by biochemical and functional assays e.g., antibody-drug conjugate (ADC) and western blot assays, including glycan studies. Results: Candidate mAb KP52 was generated from whole-cell immunisation using feline mammary carcinoma. KP52 showed strong positive binding to human cancer cells, such as breast cancer and ovarian cancer. Furthermore, KP52 demonstrated strong killing ( > 50%) as an ADC with Saporin as the payload. Western blot results revealed the molecular weight of the antigen targets to be approximately 45kD and 50kD under reduced conditions. Glycan studies suggest that the epitope is glycan in nature, specifically an O-linked glycan. Conclusion: Candidate mAb KP52 has a therapeutic potential as an ADC against feline mammary cancer, human ovarian cancer, human mammary cancer, human pancreatic cancer, and human gastric cancer.

Keywords: ADC, comparative oncology, mAb, therapeutic

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Authors: Jer-Yuh Liu, Je-Chiuan Ye, Jin-Ming Hwang

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Protein kinase C alpha (PKCα) is a key signaling molecule in human cancer development. As a therapeutic strategy, targeting PKCα is difficult because the molecule is ubiquitously expressed in non-malignant cells. PKCα is regulated by the cooperative interaction of the transcription factors myeloid zinc finger 1 (MZF-1) and Ets-like protein-1 (Elk-1) in human cancer cells. By conducting tissue array analysis, herein, we determined the protein expression of MZF-1/Elk-1/PKCα in various cancers. The data show that the expression of MZF-1/Elk-1 is correlated with that of PKCα in hepatocellular carcinoma (HCC), but not in bladder and lung cancers. In addition, the PKCα down-regulation by shRNA Elk-1 was only observed in the HCC SK-Hep-1 cells. Blocking the interaction between MZF-1 and Elk-1 through the transfection of their binding domain MZF-160–72 decreased PKCα expression. This step ultimately depressed the epithelial-mesenchymal transition potential of the HCC cells. These findings could be used to develop an alternative therapeutic strategy for patients with the PKCα-derived HCC.

Keywords: protein kinase C alpha, myeloid zinc finger 1, ets-like protein-1, hepatocellular carcinoma

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Authors: Mary Kiviiri Nakawuka, Mary Namugalu, Andrew Otiti

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BACKGROUND Cervical cancer is the fourth most common cancer in women and seventh overall among all cancers worldwide. It accounts for about 7.5% of all female-cancer deaths with 85% occurring in low and middle-income countries and the first most common female cancer in women aged 15 to 44 years in Uganda with an annual number of new cases at 3,915 and 2,275 annual number of cervical cancer deaths in 2012 (ICO INFORMATION CENTRE ON HPV AND CANCER, 2017).Despite the available free cervical cancer screening services whose uptake has been documented to improve the chances of successful treatment of pre-cancers and cancers among women of reproductive age, there is a low uptake of these services thus we sought to examine the uptake of cervical cancer services and associated factors among women of reproductive age (25-49) attending the ART clinic of KISWA HCII in Kampala, Uganda METHODS The research was carried out in the ART clinic of KISWA HCII among 385 participants. An analytical, cross-sectional study with quantitative methods of data collection was used. The study adopted a non-probability convenience sampling method to select participants. Quantitative data was collected through structured questionnaires. RESULTS 72.2% of the participants were found to have been screened for cervical cancer. 36 % of the screened women had a positive HPV or VIA result ,59.2% of the screened women had a negative HPV or VIA result and 4.8% had an invalid HPV test result. Only 39.5% of the participants had adequate overall knowledge about cervical cancer, more than a third of the participants (50%) had moderate or low knowledge and minority of them (10.5%) had no knowledge. There was no significant association between the uptake of cervical cancer screening services among participants and their socio-demographic characteristics. CONCLUSIONS Although majority of the women surveyed had been screened for cervical cancer, a comparatively large number of participants had inadequate knowledge about cervical cancer and therefore there is still need to continue teaching about cervical cancer and this may include education campaigns, improvements to the accessibility and convenience of the screening services.

Keywords: cervical cancer uptake, cervical cancer screening, women of reproductive age., cervical cancer knowledge

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Authors: Shangqing Song, Bin Xu, Yajun Cheng, Zhong Wang

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miRNAs derived from exosomes exist in a body fluid such as urine were regarded as potential biomarkers for various human cancers diagnosis and prognosis, as mature miRNAs can be steadily preserved by exosomes. However, its potential value in clear cell renal cell carcinoma (ccRCC) diagnosis and prognosis remains unclear. In the present study, differentially expressed miRNAs from urinal exosomes were identified by next-generation sequencing (NGS) technology. The 16 differentially expressed miRNAs were identified between ccRCC patients and healthy donors. To explore the specific diagnosis biomarker of ccRCC, we validated these urinary exosomes from 70 early-stage renal cancer patients, 30 healthy people and other urinary system cancers, including 30 early-stage prostate cancer patients and 30 early-stage bladder cancer patients by qRT-PCR. The results showed that urinary exosome miR-30c-5p could be stably amplified and meanwhile the expression of miR-30c-5p has no significant difference between other urinary system cancers and healthy control, however, expression level of miR-30c-5p in urinary exosomal of ccRCC patients was lower than healthy people and receiver operation characterization (ROC) curve showed that the area under the curve (AUC) values was 0.8192 (95% confidence interval was 0.7388-0.8996, P= 0.0000). In addition, up-regulating miR-30c-5p expression could inhibit renal cell carcinoma cells growth. Lastly, HSP5A was found as a direct target gene of miR-30c-5p. HSP5A depletion reversed the promoting effect of ccRCC growth casued by miR-30c-5p inhibitor, respectively. In conclusion, this study demonstrated that urinary exosomal miR-30c-5p is readily accessible as diagnosis biomarker of early-stage ccRCC, and miR-30c-5p might modulate the expression of HSPA5, which correlated with the progression of ccRCC.

Keywords: clear cell renal cell carcinoma, exosome, HSP5A, miR-30c-5p

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Authors: Ricardo Alberto Chiong Zevallos, Eduardo Moraes Rego Reis

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Pancreatic adenocarcinoma (PDAC) patients have a less than 10% 5-year survival rate. PDAC has no defined diagnostic and prognostic biomarkers. Gemcitabine is the first-line drug in PDAC and several other cancers. Long non-coding RNAs (lncRNAs) contribute to the tumorigenesis and are potential biomarkers for PDAC. Although lncRNAs aren’t translated into proteins, they have important functions. LncRNAs can decoy or recruit proteins from the epigenetic machinery, act as microRNA sponges, participate in protein translocation through different cellular compartments, and even promote chemoresistance. The chromatin remodeling enzyme EZH2 is a histone methyltransferase that catalyzes the methylation of histone 3 at lysine 27, silencing local expression. EZH2 is ambivalent, it can also activate gene expression independently of its histone methyltransferase activity. EZH2 is overexpressed in several cancers and interacts with lncRNAs, being recruited to a specific locus. EZH2 can be recruited to activate an oncogene or silence a tumor suppressor. The lncRNAs misregulation in cancer can result in the differential recruitment of EZH2 and in a distinct epigenetic landscape, promoting chemoresistance. The relevance of the EZH2-lncRNAs interaction to chemoresistant PDAC was assessed by Real Time quantitative PCR (RT-qPCR) and RNA Immunoprecipitation (RIP) experiments with naïve and gemcitabine-resistant PDAC cells. The expression of several lncRNAs and EZH2 gene targets was evaluated contrasting naïve and resistant cells. Selection of candidate genes was made by bioinformatic analysis and literature curation. Indeed, the resistant cell line showed higher expression of chemoresistant-associated lncRNAs and protein coding genes. RIP detected lncRNAs interacting with EZH2 with varying intensity levels in the cell lines. During RIP, the nuclear fraction of the cells was incubated with an antibody for EZH2 and with magnetic beads. The RNA precipitated with the beads-antibody-EZH2 complex was isolated and reverse transcribed. The presence of candidate lncRNAs was detected by RT-qPCR, and the enrichment was calculated relative to INPUT (total lysate control sample collected before RIP). The enrichment levels varied across the several lncRNAs and cell lines. The EZH2-lncRNA interaction might be responsible for the regulation of chemoresistance-associated genes in multiple cancers. The relevance of the lncRNA-EZH2 interaction to PDAC was assessed by siRNA knockdown of a lncRNA, followed by the analysis of the EZH2 target expression by RT-qPCR. The chromatin immunoprecipitation (ChIP) of EZH2 and H3K27me3 followed by RT-qPCR with primers for EZH2 targets also assess the specificity of the EZH2 recruitment by the lncRNA. This is the first report of the interaction of EZH2 and lncRNAs HOTTIP and PVT1 in chemoresistant PDAC. HOTTIP and PVT1 were described as promoting chemoresistance in several cancers, but the role of EZH2 is not clarified. For the first time, the lncRNA LINC01133 was detected in a chemoresistant cancer. The interaction of EZH2 with LINC02577, LINC00920, LINC00941, and LINC01559 have never been reported in any context. The novel lncRNAs-EZH2 interactions regulate chemoresistant-associated genes in PDAC and might be relevant to other cancers. Therapies targeting EZH2 alone weren’t successful, and a combinatorial approach also targeting the lncRNAs interacting with it might be key to overcome chemoresistance in several cancers.

Keywords: epigenetics, chemoresistance, long non-coding RNAs, pancreatic cancer, histone modification

Procedia PDF Downloads 60

Authors: Michio Kurosu

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Alterations in glycosylation not only directly impact cell growth and survival but also facilitate tumor-induced immunomodulation and eventual metastasis. Identification of cell type-specific glycoconjugates (tumor markers) has led to the discovery of new assay systems for certain cancers via immunodetection reagents. N- and O-linked glycans are the most abundant forms of glycoproteins. Recent studies of cancer immunotherapy are based on the immunogenicity of truncated O-glycan chains (e.g., Tn, sTn, T, and sLea/x). The prevalence of N-linked glycan changes in the development of tumor cells is known; however, therapeutic antibodies against N-glycans have not yet been developed. This is due to the lack of specificity of N-linked glycans between normal/healthy and cancer cells. Abnormal branching of N-linked glycans has been observed, particularly in solid cancer cells. While the discovery of drug-like glycosyltransferase inhibitors that block the biosynthesis of specific branching has a very low likelihood of success, altered glycosylation levels can be exploited by suppressing N-glycan biosynthesis through the inhibition of dolichyl-phosphate N-acetylglucosaminephosphotransferase1 (DPAGT1) activity. Inhibition of DPAGT1 function leads to changes of O-glycosylation on proteins associated with mitochondria and zinc finger binding proteins (indirect effects). On the basis of dynamic crosstalk between DPAGT1 and Snail/Slung/ZEB1 (a family of transcription factors that promote the repression of the adhesion molecules), we have developed pharmacologically acceptable selective DPAGT1 inhibitors. Tunicamycin kills a wide range of cancer and healthy cells in a non-selective manner. In sharp contrast, our DPAGT1 inhibitors display strong cytostatic effects against 16 solid cancers, which require the overexpression of DPAGT1 in their progression but do not affect the cell viability of healthy cells. The identified DPAGT1 inhibitors possess impressive anti-metastatic ability in various solid cancer cell lines and induce their mitochondrial structural changes, resulting in apoptosis. A prototype DPAGT1 inhibitor, APPB has already been proven to shrink solid tumors (e.g., pancreatic cancers, triple-negative breast cancers) in vivo while suppressing metastases and has strong synergistic effects when combined with current cytotoxic drugs (e.g., paclitaxel). At this conference, our discovery of selective DPAGT1 inhibitors with drug-like properties and proof-of-pharmaceutical concept studies of a novel DPAGT1 inhibitor are presented.

Keywords: DPAGT1 inhibitors, anti-metastatic drugs, natural product based drug designs, cytostatic effects

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