Search results for: gynecological cancers

Authors: Soodabeh Shahid Sales, Azam Rastgar Moghadam, Mehrane Mehramiz, Malihe Entezari, Kazem Anvari, Mohammad Sadegh Khorrami, Saeideh Ahmadi Simab, Ali Moradi, Seyed Mahdi Hassanian, Majid Ghayour-Mobarhan, Gordon A. Ferns, Amir Avan

Abstract:

Background Esophageal cancer has been reported as the eighth most common cancer universal and the seventh cause of cancer-related death in men .recent studies have revealed that cytochrome P450, family 1, subfamily B, polypeptide 1, which plays a role in metabolizing xenobiotics, is associated with different cancers. Therefore in the present study, we investigated the impact of CYP1B1-rs1056836 on esophagus squamous cell carcinoma (ESCC) patients. Method: 317 subjects, with and without ESCC were recruited. DNA was extracted and genotyped via Real-time PCR-Based Taq Man. Kaplan Meier curves were utilized to assess overall and progression-free survival. To evaluate the relationship between patients clinicopathological data, genotypic frequencies, disease prognosis, and patients survival, Pearson chi-square and t-test were used. Logistic regression was utilized to assess the association between the risk of ESCC and genotypes. Results: the genotypic frequency for GG, GC, and CC are respectively 58.6% , 29.8%, 11.5% in the healthy group and 51.8%, 36.14% and 12% in ESCC group. With respect to the recessive genetic inheritance model, an association between the GG genotype and stage of ESCC were found. Also, statistically significant results were not found for this variation and risk of ESCC. Patients with GG genotype had a decreased risk of nodal metastasis in comparison with patients with CC/CG genotype, although this link was not statistically significant. Conclusion: Our findings illustrated the correlation of CYP1B1-rs1056836 as a potential biomarker for ESCC patients, supporting further studies in larger populations in different ethnic groups. Moreover, further investigations are warranted to evaluate the association of emerging marker with dietary intake and lifestyle.

Keywords: Cytochrome P450, esophagus squamous cell carcinoma, dietary intake, lifestyle

Procedia PDF Downloads 185

Authors: Rolivhuwa Bishop Ramagoma1*, Lynn Cairncross1, , Saartjie Roux1

Abstract:

According to the world health organisation, colon cancer is among the most common cancers diagnosed in both men and women. Specifically, it is the second leading cause of cancer related deaths accounting for over 860 000 deaths worldwide in 2018. Currently, chemotherapy has become an essential component of most cancer treatments. Despite progress in cancer drug development over the previous years, traditional chemotherapeutic drugs still have low selectivity for targeting tumour tissues and are frequently constrained by dose-limiting toxicity. The creation of nanoscale delivery vehicles capable of directly directing treatment into cancer cells has recently caught the interest of researchers. Herein, the development of peptide-functionalized polyethylene glycol gold nanoparticles (Peptide-PEG-AuNPs) as a cellular probe and delivery agent is described, with the higher aim to develop a specific diagnostic prototype and assess their specificity not only against cell lines but primary human cells as well. Gold nanoparticles (AuNPs) were synthesized and stabilized through chemical conjugation. The synthesized AuNPs were characterized, stability in physiological solutions was assessed, their cytotoxicity against colon carcinoma and non-carcinoma skin fibroblasts was also studied. Furthermore, genetic effect through real-time polymerase chain reaction (RT-PCR), localization and uptake, peptide specificity were also determined. In this study, different peptide-AuNPs were found to have preferential toxicity at higher concentrations, as revealed by cell viability assays, however, all AuNPs presented immaculate stability for over 3 months following the method of synthesis. The final obtained peptide-PEG-AuNP conjugates showed good biocompatibility in the presence of high ionic solutions and biological media and good cellular uptake. Formulation of colon cancer specific targeting peptide was successful, additionally, the genes/pathways affected by the treatments were determined through RT-PCR. Primary cells study is still on going with promising results thus far.

Keywords: nanotechnology, cancer, diagnosis, therapeutics, gold nanoparticles.

Procedia PDF Downloads 66

Authors: Hossein Rassi, Marjan Moradi Fard, Masoud Houshmand

Abstract:

Background: Cervical cancer is multistep disease that is thought to result from an interaction between genetic background and environmental factors. Human papillomavirus (HPV) infection is the leading risk factor for cervical intraepithelial neoplasia(CIN)and cervical cancer. In other hand, some of p53 and miRNA polymorphism may plays an important role in carcinogenesis. This study attempts to clarify the relation of p53 genotypes and miR-146a rs2910164 polymorphism in cervical lesions. Method: Forty two archival samples with cervical lesion retired from Khatam hospital and 40 sample from healthy persons used as control group. A simple and rapid method was used to detect the simultaneous amplification of the HPV consensus L1 region and HPV-16,-18, -11, -31, 33 and -35 along with the b-globin gene as an internal control. We use Multiplex PCR for detection of P53 and miR-146a rs2910164 genotypes in our lab. Finally, data analysis was performed using the 7 version of the Epi Info(TM) 2012 software and test chi-square(x2) for trend. Results: Cervix lesions were collected from 42 patients with Squamous metaplasia, cervical intraepithelial neoplasia, and cervical carcinoma. Successful DNA extraction was assessed by PCR amplification of b-actin gene (99bp). According to the results, p53 GG genotype and miR-146a rs2910164 CC genotype was significantly associated with increased risk of cervical lesions in the study population. In this study, we detected 13 HPV 18 from 42 cervical cancer. Conclusion: The connection between several SNP polymorphism and human virus papilloma in rare researches were seen. The reason of these differences in researches' findings can result in different kinds of races and geographic situations and also differences in life grooves in every region. The present study provided preliminary evidence that a p53 GG genotype and miR-146a rs2910164 CC genotype may effect cervical cancer risk in the study population, interacting synergistically with HPV 18 genotype. Our results demonstrate that the testing of p53 codon 72 polymorphism genotypes and miR-146a rs2910164 polymorphism genotypes in combination with HPV18 can serve as major risk factors in the early identification of cervical cancers. Furthermore, the results indicate the possibility of primary prevention of cervical cancer by vaccination against HPV18 in Iran.

Keywords: cervical cancer, p53, miR-146a, rs2910164, polymorphism

Procedia PDF Downloads 454

Authors: Hossein Rassi, Marjan Moradi fard, Masoud Houshmand

Abstract:

Background: Cervical cancer is multistep disease that is thought to result from an interaction between genetic background and environmental factors. Human Papillomavirus (HPV) infection is the leading risk factor for Cervical Intraepithelial Neoplasia (CIN) and cervical cancer. In other hand, some of p53 and miRNA polymorphism may plays an important role in carcinogenesis. This study attempts to clarify the relation of p53 genotypes and miR-146a rs2910164 polymorphism in cervical lesions. Method: Forty two archival samples with cervical lesion retired from Khatam hospital and 40 sample from healthy persons used as control group. A simple and rapid method was used to detect the simultaneous amplification of the HPV consensus L1 region and HPV-16,-18, -11, -31, 33, and -35 along with the b-globin gene as an internal control. We use Multiplex PCR for detection of P53 and miR-146a rs2910164 genotypes in our lab. Finally, data analysis was performed using the 7 version of the Epi Info(TM) 2012 software and test chi-square(x2) for trend. Results: Cervix lesions were collected from 42 patients with Squamous metaplasia, cervical intraepithelial neoplasia, and cervical carcinoma. Successful DNA extraction was assessed by PCR amplification of b-actin gene (99 bp). According to the results, p53 GG genotype and miR-146a rs2910164 CC genotype was significantly associated with increased risk of cervical lesions in the study population. In this study, we detected 13 HPV 18 from 42 cervical cancer. Conclusion: The connection between several SNP polymorphism and human virus papilloma in rare researches were seen. The reason of these differences in researches' findings can result in different kinds of races and geographic situations and also differences in life grooves in every region. The present study provided preliminary evidence that a p53 GG genotype and miR-146a rs2910164 CC genotype may effect cervical cancer risk in the study population, interacting synergistically with HPV 18 genotype. Our results demonstrate that the testing of p53 codon 72 polymorphism genotypes and miR-146a rs2910164 polymorphism genotypes in combination with HPV18 can serve as major risk factors in the early identification of cervical cancers. Furthermore, the results indicate the possibility of primary prevention of cervical cancer by vaccination against HPV18 in Iran.

Keywords: cervical cancer, miR-146a rs2910164 polymorphism, p53 polymorphism, intraepithelial, neoplasia, HPV

Procedia PDF Downloads 384

Authors: Siti Rahmawati

Abstract:

Indonesia has had long period of monetary economic crisis and it is followed by an upward trend in the price of fuel oil. This situation impacts all aspects of tuna fishermen community. For instance, the basic needs of fishing communities increase and the lower purchasing power then lead to economic and social instability as well as the health of fishermen household. To understand this AHP method is applied to acknowledge the model of tuna fisheries management priorities and cold chain marketing channel and the utilization levels that impact on human health. The study is designed as a development research with the number of 180 respondents. The data were analyzed by Analytical Hierarchy Process (AHP) method. The development of tuna fishery business can improve productivity of production with economic empowerment activities for coastal communities, improving the competitiveness of products, developing fish processing centers and provide internal capital for the development of optimal fishery business. From economic aspects, fishery business is more attracting because the benefit cost ratio of 2.86. This means that for 10 years, the economic life of this project can work well as B/C> 1 and therefore the rate of investment is economically viable. From the health aspects, tuna can reduce the risk of dying from heart disease by 50%, because tuna contain selenium in the human body. The consumption of 100 g of tuna meet 52.9% of the selenium in the body and activating the antioxidant enzyme glutathione peroxidaxe which can protect the body from free radicals and stimulate various cancers. The results of the analytic hierarchy process that the quality of tuna products is the top priority for export quality as well as quality control in order to compete in the global market. The implementation of the policy can increase the income of fishermen and reduce the poverty of fishermen households and have impact on the human health whose has high risk of disease.

Keywords: management of tuna, social, economic, health

Procedia PDF Downloads 303

Authors: Nusrat Praween, Krishna Thej Pammi Guru, Palash Kumar Basu

Abstract:

Designing non-invasive biosensors for cancer diagnosis is essential for developing an affordable and specific tool to measure cancer-related exosome biomarkers. Exosomes, released by healthy as well as cancer cells, contain valuable information about the biomarkers of various diseases, including cancer. Despite the availability of various isolation techniques, ultracentrifugation is the standard technique that is being employed. Post isolation, exosomes are traditionally exposed to detergents for extracting their proteins, which can often lead to protein degradation. Further to this, it is very essential to develop a sensing platform for the quantification of clinically relevant proteins in a wider range to ensure practicality. In this study, exosomes were immobilized on the Au Screen Printed Electrode (SPE) using EDC/NHS chemistry to facilitate binding. After immobilizing the exosomes on the screen-printed electrode (SPE), we investigated the impact of the electric field by applying various voltages to induce exosome lysis and release their contents. The lysed solution was used for sensing TSG101, a crucial biomarker associated with various cancers, using both faradaic and non-faradaic electrochemical impedance spectroscopy (EIS) methods. The results of non-faradaic and faradaic EIS were comparable and showed good consistency, indicating that non-faradaic sensing can be a reliable alternative. Hence, the non-faradaic sensing technique was used for label-free quantification of the TSG101 biomarker. The results were validated using ELISA. Our electrochemical immunosensor demonstrated a consistent response of TSG101 from 125 pg/mL to 8000 pg/mL, with a detection limit of 0.125 pg/mL at room temperature. Additionally, since non-faradic sensing is label-free, the ease of usage and cost of the final sensor developed can be reduced. The proposed immunosensor is capable of detecting the TSG101 protein at low levels in healthy serum with good sensitivity and specificity, making it a promising platform for biomarker detection.

Keywords: biosensor, exosomes isolation on SPE, electric field lysis of exosome, EIS sensing of TSG101

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Authors: Rofida Gamal, Mostafa Mohammed, Mariam Adel, Marwa Gamal, Marwa kamal, Ayat Saber, Maha Mamdouh, Amira Emad, Mai Ramadan

Abstract:

Lynch Syndrome is an inherited genetic condition associated with an increased risk of colorectal and other cancers. Detecting Lynch Syndrome in individuals is crucial for early intervention and preventive measures. This study proposes a computational pipeline for Lynch Syndrome detection by integrating alignment, variant calling, and annotation. The pipeline leverages popular tools such as FastQC, Trimmomatic, BWA, bcftools, and ANNOVAR to process the input FASTQ file, perform quality trimming, align reads to the reference genome, call variants, and annotate them. It is believed that the computational pipeline was applied to a dataset of Lynch Syndrome cases, and its performance was evaluated. It is believed that the quality check step ensured the integrity of the sequencing data, while the trimming process is thought to have removed low-quality bases and adaptors. In the alignment step, it is believed that the reads were accurately mapped to the reference genome, and the subsequent variant calling step is believed to have identified potential genetic variants. The annotation step is believed to have provided functional insights into the detected variants, including their effects on known Lynch Syndrome-associated genes. The results obtained from the pipeline revealed Lynch Syndrome-related positions in the genome, providing valuable information for further investigation and clinical decision-making. The pipeline's effectiveness was demonstrated through its ability to streamline the analysis workflow and identify potential genetic markers associated with Lynch Syndrome. It is believed that the computational pipeline presents a comprehensive and efficient approach to Lynch Syndrome detection, contributing to early diagnosis and intervention. The modularity and flexibility of the pipeline are believed to enable customization and adaptation to various datasets and research settings. Further optimization and validation are believed to be necessary to enhance performance and applicability across diverse populations.

Keywords: Lynch Syndrome, computational pipeline, alignment, variant calling, annotation, genetic markers

Procedia PDF Downloads 55

Authors: Vitor Rafael Regiani, Carlos Henrique Viesi Do Nascimento Filho, Patricia Matos Biselli-Chicote, Claudia Aparecida Rainho, Luiz Sergio Raposo, José Victor Maniglia, Eny Maria Goloni-Bertollo, Erika Cristina Pavarino

Abstract:

Promoter hypermethylation of tumor-related genes has been associated with prognosis in early-stage head-and-neck cancers, providing strong evidence that these hypermethylated genes are valuable biomarkers for prognostic evaluation. Hence, we selected the MGMT and RASSF1A genes to examine the methylation status in head and neck squamous cell carcinomas (HNSCC) samples matched with non-tumor tissues (tumor-surrounding tissues or peripheral blood samples). DNA methylation analysis was based on Methylation-Sensitive High Resolution Melting, and the methylation status was correlated with clinic-pathological characteristics of the patients. RASSF1A and MGMT promoter methylation was detected in 43.24% (16/37) and in 44.44% (16/36) of the tumors, respectively. RASSF1A and MGMT methylation was significantly more frequent in tumor tissue than non-tumor tissues, as well as, simultaneous methylation of RASSF1A and MGMT also was higher in tumor tissue than non-tumor tissues. In relation to anatomic site, larynx cancer presented significant methylation of MGMT gene compared to tumor-surrounding tissue. The frequency of RASSF1A and MGMT promoter methylated was higher in tumor tissues in relation to peripheral blood from the same patient. No association was found between methylation and the variables analyzed, including gender, age, smoking or alcohol drinking habits. Clinic-pathological characteristics also showed no association in the presence of methylation. The Kaplan–Meier's method showed no association of methylation and both disease-free and overall survival. In conclusion, the presence of epigenetic abnormalities in normal-appearing tissue corroborates the hypothesis of the ‘field cancerization', or it can reflect preneoplastic and/or preinvasive. Moreover, MGMT methylation may serve as an important laryngeal cancer biomarker because it showed significant difference between laryngeal cancer and surrounding tumor tissues.

Keywords: head and neck cancer, DNA methylation, MGMT promoter methylation, RASSF1A promoter methylation

Procedia PDF Downloads 301

Authors: Pei-Chih Wu, Hsin-Chih Lai, Yung-Lung Lee, Yun-Yao Chi, Ching-Yi Horng, Hsien-Chang Wang

Abstract:

The impact of climate change to health has always been well documented. Amongst them, water-borne infectious diseases, chronic adverse effects or cancer risks due to chemical contamination in flooding or drought events are especially important in river basin. This study therefore utilizes GIS and different models to integrate demographic, land use, disaster prevention, social-economic factors, and human health assessment in the Erren River basin. Therefore, through the collecting of climatic, demographic, health surveillance, water quality and other water monitoring data, potential risks associated with the Erren River Basin are established and to understand human exposure and vulnerability in response to climate extremes. This study assesses the temporal and spatial patterns of melioidosis (2000-2015) and various cancer incidents in Tainan and Kaohsiung cities. The next step is to analyze the spatial association between diseases incidences, climatic factors, land uses, and other demographic factors by using ArcMap and GeoDa. The study results show that amongst all melioidosis cases in Taiwan, 24% cases (115) residence occurred in the Erren River basin. The relationship between the cases and in Tainan and Kaohsiung cities are associated with population density, aging indicator, and residence in Erren River basin. Risks from flooding due to heavy rainfall and fish farms in spatial lag regression are also related. Through liver cancer, the preliminary analysis in temporal and spatial pattern shows an increases pattern in annual incidence without clusters in Erren River basin. Further analysis of potential cancers connected to heavy metal contamination from water pollution in Erren River is established. The final step is to develop an assessment tool for human exposure from water contamination and vulnerability in response to climate extremes for the second year.

Keywords: climate change, health impact, health adaptation, Erren River Basin

Procedia PDF Downloads 289

Authors: Hossein Rassi, Marjan Moradi Fard, Masoud Houshmand

Abstract:

Background: Cervical cancer is multistep disease that is thought to result from an interaction between genetic background and environmental factors. Human papillomavirus (HPV) infection is the leading risk factor for cervical intraepithelial neoplasia (CIN) and cervical cancer. In other hand, some of p53 and miRNA polymorphism may plays an important role in carcinogenesis. This study attempts to clarify the relation of p53 genotypes and miR-146a rs2910164 polymorphism in cervical lesions. Method: Forty two archival samples with cervical lesion retired from Khatam hospital and 40 sample from healthy persons used as control group. A simple and rapid method was used to detect the simultaneous amplification of the HPV consensus L1 region and HPV-16,-18, -11, -31, 33 and -35 along with the b-globin gene as an internal control. We use Multiplex PCR for detection of P53 and miR-146a rs2910164 genotypes in our lab. Finally, data analysis was performed using the 7 version of the Epi Info(TM) 2012 software and test chi-square(x2) for trend. Results: Cervix lesions were collected from 42 patients with Squamous metaplasia, cervical intraepithelial neoplasia, and cervical carcinoma. Successful DNA extraction was assessed by PCR amplification of b-actin gene (99bp). According to the results, p53 GG genotype and miR-146a rs2910164 CC genotype was significantly associated with increased risk of cervical lesions in the study population. In this study, we detected 13 HPV 18 from 42 cervical cancer. Conclusion: The connection between several SNP polymorphism and human virus papilloma in rare researches were seen. The reason of these differences in researches' findings can result in different kinds of races and geographic situations and also differences in life grooves in every region. The present study provided preliminary evidence that a p53 GG genotype and miR-146a rs2910164 CC genotype may effect cervical cancer risk in the study population, interacting synergistically with HPV 18 genotype. Our results demonstrate that the testing of p53 codon 72 polymorphism genotypes and miR-146a rs2910164 polymorphism genotypes in combination with HPV18 can serve as major risk factors in the early identification of cervical cancers. Furthermore, the results indicate the possibility of primary prevention of cervical cancer by vaccination against HPV18 in Iran.

Keywords: cervical cancer, HPV18, p53 codon 72 polymorphism, miR-146a rs2910164 polymorphism

Procedia PDF Downloads 441

Authors: Razieh Zarei, Hassan zm, Abolghasem Ajami, Darush Moslemi, Narges Afsary, Amrollah Mostafa-zade

Abstract:

Introduction: IL-23 is responsible for the differentiation and expansion of Th17/ThIL-17 cells from naive CD4+ T cells. Therefore, may be IL-23/IL17 axis involve in a variety of allergic and autoimmune diseases, such as RA, MS, inflammatory bowel disease (IBD), and asthma. TGF-β is also share for the differentiation Th17 producing IL-17 and CD4+CD25+Foxp3hiT regulatory cells from naïve CD4+ T cells which are involved in the regulation of immune response, maintaining immunological self-tolerance and immune homeostasis ,and the control of autoimmunity and cancer surveillance. Therefore, T regulatory cells play a key role in autoimmunity, allergy, cancer, infectious disease, and the induction of transplantation tolerance. Vitamin A and it's derivatives (retinoids) inhibit or reverse the carcinogenic process in some types of cancers in oral cavity,head and neck, breast, skin, liver, and blood cells. Shark is a murine organism and its cartilage has antitumor peptides to prevent angiogenesis, in vitro. Our purpose is whether simultaneous oral treatment vitamin A and shark cartilage can modulate IL-23/IL-17 and CD4CD25Foxp3 T regulatory cell/TGF-β pathways and Th1/Th2 immunity in patients with gastric cancer. Materials and Methods: First investigated an imbalanced supernatant of cytokines exist in patients with gastric cancer by ELISA. Associated with cytokines measuring such as IL-23,IL-17,TGF-β,IL-4 and γ-IFN, then flow cytometry was employed to determine whether the peripheral blood mononuclear cells such as CD4+CD25+Foxp3highT regulatory cells in patients with gastric cancer were changed correspondingly. Results: An imbalance between IL-17 secretion and TGF-β/Foxp3 t regulatory cell pathway and so, Th1 immunity (γ-IFN production) and TH2 immunity (IL-4 secretion) was not seen in patients with gastric cancer treated by vitamin A and shark cartilage. But, the simultaneously presented down-regulation of IL-23 indicated, at least cytokine level. Conclusion: Il-23, as a pro-angiogenesis cytokine, probably, help to tumor growth. Hence, suggested that down-regulation of IL-23, at least cytokine level, is useful for anti-tumor immune responses in patients with gastric cancer.

Keywords: IL-23/IL17 axis, TGF-β/CD4CD25Foxp3 T regulatory pathway, γ-IFN, IL-4, shark cartilage and gastric cancer

Procedia PDF Downloads 380

Authors: Grzegorz Swiderski, Agata Jablonska-Trypuc, Natalia Popow, Renata Swislocka, Wlodzimierz Lewandowski

Abstract:

Doxorubicin belongs to the group of anthracycline antitumor antibiotics. Because of the wide spectrum of actions, it is one of the most widely used anthracycline antibiotics, including the treatment of breast, ovary, bladder, lung cancers as well as neuroblastoma, lymphoma, leukemia and myeloid leukemia. Antitumor activity of doxorubicin is based on the same mechanisms as for most anthracyclines. Like the metal ions affect the nucleic acids on many biological processes, so the environment of the metal chelates of antibiotics can have a significant effect on the pharmacological properties of drugs. Complexation of anthracyclines with metal ions may contribute to the production of less toxic compounds. In the framework of this study, the composition of complexes obtained in aqueous solutions of doxorubicin with metal ions (Cu2+ and Zn2+). Complexation was analyzed by spectrophotometric titration in aqueous solution at pH 7.0. The pH was adjusted with 0.02M Tris-HCl buffer. The composition of the complexes found was Cu: doxorubicin (1: 2) and a Zn: doxorubicin (1: 1). The effect of Dox, Dox-Cu and Dox-Zn was examined in MCF-7 breast cancer cell line, which were obtained from American Type Culture Collection (ATCC). The compounds were added to the cultured cells for a final concentration in the range of 0,01µM to 0,5µM. The number of MCF-7 cells with division into living and dead, was determined by direct counts of cells with the use of trypan blue dye using LUNA Logos Biosystems cell counter. ApoTox-Glo Triplex Assay (Promega, Madison, Wisconsin, USA) was used according to the manufacturer’s instructions to measure the MCF-7 cells’ viability, cytotoxicity and apoptosis. We observed a decrease in cells proliferation in a dose-dependent manner. An increase in cytotoxicity and decrease in viability in the ApoTox Triplex assay was also showed for all tested compounds. Apoptosis, showed as caspase 3/7 activation, was observed only in Dox treatment. In Dox-Zn and Dox-Cu caspase 3/7 activation was not observed. This work was financially supported by National Science Centre, Poland, under the research project number 2014/13/B/NZ7/02 352.

Keywords: anticancer properties, anthracycline antibiotic, doxorubicine, metal complexes

Procedia PDF Downloads 260

Authors: Manjusha R. Vagal, Shyam K. Shrivastava, Umesh Mahantshetty, Sudeep Gupta, Supriya Chopra, Reena Engineer, Amita Maheshwari, Atul Buduk

Abstract:

Vaginal stenosis is a common side effect associated with pelvic radiotherapy in cervical cancer patients which contributes negatively to woman’s health and prevents adequate vaginal/cervical examination. Vaginal dilation with a dilator is routine practice and is internationally advocated as a prophylactic measure to preserve vaginal patency. This retrospective study was carried out with the aim to know the usefulness of vaginal dilation following pelvic radiation therapy in cervical cancer patients in India. Data from medical records of 183 cervical cancer patients, which met the study criteria, were collected related to the stage of the disease, treatment received, commencement period of dilation post radiation therapy, sexual status and side effects associated to dilation practice. Data related to vaginal dimensions as per the length of insertion of a small, medium and large dilator were collected on regular follow-ups until 36 months and/or more. Vaginal dimensions as measured with the length of medium dilator insertion were used for analysis of dilation therapy results using paired t-test. Patients who underwent vaginal dilation with dilator maintained vaginal patency, also the mean vaginal length significantly increased, from 8.02 cm ± 2.69 to 9.96 ± 2.89 cm with a p value <0.001. There was no significant difference found on vaginal patency with different intervals of initiation of dilation therapy. At the third year and more following dilation therapy, significant increase in vaginal length observed with a p value of 0.0001 in both sexually active and inactive patients. Compilation of vaginal dosage during brachytherapy was inadequate, and hence, the secondary objective of the study to determine the effect of radiotherapy on the outcome of rehabilitation intervention was not studied in detail. This retrospective study has found that dilation therapy with vaginal dilators post pelvic radiotherapy is effective in preventing vaginal stenosis and improving vaginal patency and cannot be substituted with vaginal intercourse. Sexual quality of life assessment in the Indian population needs much attention.

Keywords: dilator, sexually active, vaginal dilation, vaginal stenosis

Procedia PDF Downloads 188

Authors: Akbar Haghzadeh Saraskanroud, Amir Hossein Yahyavi Zanjani, Niloofar Kargar, Hanieh Ahrabi

Abstract:

Cervical cancer refers to an unusual growth of cells in the cervix. The cervix is the lower part of the uterus, which connects to the vagina. Various risk factors such as human papillomavirus (HPV), having a weakened immune system, smoking or breathing in secondhand smoke, reproductive factors, and obesity play important roles in causing most cervical cancers. When cervical cancer happens, surgery is often the first treatment option to remove it. Other treatments might include chemotherapy and targeted therapy medicines. Radiation therapy with high-energy photon beams also may be used. Sometimes combined treatment, including radiation with low-dose chemotherapy, was applied. Intracavitary brachytherapy is an integral part of radiotherapy for locally advanced gynecologic malignancies such as cervical cancer. In the treatment of cervical cancer, there are different tools for doing brachytherapy. Two combinations of different applicators for this purpose are Tandem and Ovoid and Tandem and Ring. This study evaluated the dose differences between these two methods in the organs at risk of the rectum, sigmoid, and bladder. In this study, the treatment planswere simulated by the Oncentra treatment planning system and Tandem, Ovid, and Rings of different sizes. CT scan images of 23 patients were treated with HDR_BT Elekta Flexitron system were used for this study. Contouring of HR-CTV, rectum and bladder was performed for all patients. Then, the received dose of 0.1 and 0.2cc volumes of organs at risk were obtained and compared for these two methods: T-Ovoid and T-Ring. By doing investigations and dose measurements of points A and B and the volumes specified by ICRU, it seems that when comparing ring and ovoid to tandem and ovoid, the total dose to the rectum was lower by about 11%, and the bladder was 7%. In the case of HR CTV, this comparison showed that this ratio is about 7% better. Figure 1 shows the amount of decrease in rectum dose in the T-Ring method compared to T-Ovoid. Figure 2 indicates the amount of decrease in bladder dose in the T-Ring method compared to T-Ovoid. Finally, figure 3 illustrates the amount of HR-CTV coverage in the T-Ring method compared to the T-Ovoid.

Keywords: cervical cancer, brachytherapy, rectum, tandem and ovoid, tandem and ring.

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Authors: Hossein Rassi, Alaheh Gholami Roud-Majany, Zahra Razavi, Massoud Hoshmand

Abstract:

Cervical cancer is multi step disease that is thought to result from an interaction between genetic background and environmental factors. Human papillomavirus (HPV) infection is the leading risk factor for cervical intraepithelial neoplasia (CIN)and cervical cancer. In other hand, some of hTERT and miRNA polymorphism may plays an important role in carcinogenesis. This study attempts to clarify the relation of hTERT genotypes and miR-146a genotypes in cervical cancer. Forty two archival samples with cervical lesion retired from Khatam hospital and 40 sample from healthy persons used as control group. A simple and rapid method was used to detect the simultaneous amplification of the HPV consensus L1 region and HPV-16,-18, -11, -31, 33 and -35 along with the b-globin gene as an internal control. We use Multiplex PCR for detection of hTERT and miR-146a rs2910164 genotypes in our lab. Finally, data analysis was performed using the 7 version of the Epi Info(TM) 2012 software and test chi-square(x2) for trend. Cervix lesions were collected from 42 patients with Squamous metaplasia, cervical intraepithelial neoplasia, and cervical carcinoma. Successful DNA extraction was assessed by PCR amplification of b-actin gene (99bp). According to the results, hTERT ( rs 2736098) GG genotype and miR-146a rs2910164 CC genotype was significantly associated with increased risk of cervical cancer in the study population. In this study, we detected 13 HPV 18 from 42 cervical cancer. The connection between several SNP polymorphism and human virus papilloma in rare researches were seen. The reason of these differences in researches' findings can result in different kinds of races and geographic situations and also differences in life grooves in every region. The present study provided preliminary evidence that a p53 GG genotype and miR-146a rs2910164 CC genotype may effect cervical cancer risk in the study population, interacting synergistically with HPV 18 genotype. Our results demonstrate that the testing of hTERT rs 2736098 genotypes and miR-146a rs2910164 genotypes in combination with HPV18 can serve as major risk factors in the early identification of cervical cancers. Furthermore, the results indicate the possibility of primary prevention of cervical cancer by vaccination against HPV18 in Iran.

Keywords: polymorphism of hTERT gene, miR-146a rs2910164 polymorphism, cervical cancer, virus

Procedia PDF Downloads 302

Authors: Shoukat Ali, Amjad Hussain, Latif-ur-Rehman, Sehrish Inam

Abstract:

Radiotherapy plays an important role in the management of cancer patients. Approximately 50% of the cancer patients receive radiotherapy at one point or another during the course of treatment. The entire radiotherapy treatment of curative intent is divided into different phases, depending on the histology of the tumor. The established protocols are useful in deciding the total dose, fraction size, and numbers of phases. The objective of this study was to evaluate the dosimetric differences between the conventional treatment protocols and the three-dimensional conformal simultaneously integrated boost (SIB) plans for three different tumors sites (i.e. bladder, breast, and brain). A total of 30 patients with brain, breast and bladder cancers were selected in this retrospective study. All the patients were CT simulated initially. The primary physician contoured PTV1 and PTV2 in the axial slices. The conventional doses prescribed for brain and breast is 60Gy/30 fractions, and 64.8Gy/36 fractions for bladder treatment. For the SIB plans biological effective doses (BED) were calculated for 25 fractions. The two conventional (Phase I and Phase II) and a single SIB plan for each patient were generated on Eclipse™ treatment planning system. Treatment plans were compared and analyzed for coverage index, conformity index, homogeneity index, dose gradient and organs at risk doses.In both plans 95% of PTV volume received a minimum of 95% of the prescribe dose. Dose deviation in the optic chiasm was found to be less than 0.5%. There is no significant difference in lung V20 and heart V30 in the breast plans. In the rectum plans V75%, V50% and V25% were found to be less than 1.2% different. Deviation in the tumor coverage, conformity and homogeneity indices were found to be less than 1%. SIB plans with three dimensional conformal radiotherapy technique reduce the overall treatment time without compromising the target coverage and without increasing dose to the organs at risk. The higher dose per fraction may increase the late effects to some extent. Further studies are required to evaluate the late effects with the intention of standardizing the SIB technique for practical implementation.

Keywords: coverage index, conformity index, dose gradient, homogeneity index, simultaneously integrated boost

Procedia PDF Downloads 459

Authors: Nima Samie, Batoul Sadat Haerian, Sekaran Muniandy, M. S. Kanthimathi

Abstract:

Colon and breast cancers are categorized as the most prevalent types of cancer worldwide. Recently, the broad clinical application of metal complex compounds has led to the discovery of potential therapeutic drugs. The aim of this study was to evaluate the cytotoxic action of a selected nickel complex compound (NCC) against human colon and breast cancer cells. In this context, we determined the potency of the compound in the induction of apoptosis, cell cycle arrest, and cytoskeleton rearrangement. HT-29, WiDr, CCD-18Co, MCF-7 and Hs 190.T cell lines were used to determine the IC50 of the compound using the MTT assay. Analysis of apoptosis was carried out using immunofluorescence, acridine orange/ propidium iodide double staining, Annexin-V-FITC assay, evaluation of the translocation of NF-kB, oxygen radical antioxidant capacity, quenching of reactive oxygen species content , measurement of LDH release, caspase-3/-7, -8 and -9 assays and western blotting. The cell cycle arrest was examined using flowcytometry and gene expression was assessed using qPCR array. Results showed that our nickel complex compound displayed a potent suppressive effect on HT-29, WiDr, MCF-7 and Hs 190.T after 24 h of treatment with IC50 value of 2.02±0.54, 2.13±0.65, 3.76±015 and 3.14±0.45 µM respectively. This cytotoxic effect on normal cells was insignificant. Dipping in the mitochondrial membrane potential and increased release of cytochrome c from the mitochondria indicated induction of the intrinsic apoptosis pathway by the nickel complex compound. Activation of this pathway was further evidenced by significant activation of caspase 9 and 3/7.The nickel complex compound (NCC) was also shown activate the extrinsic pathways of apoptosis by activation of caspase-8 which is linked to the suppression of NF-kB translocation to the nucleus. Cell cycle arrest in the G1 phase and up-regulation of glutathione reductase, based on excessive ROS production were also observed. The results of this study suggest that the nickel complex compound is a potent anti-cancer agent inducing both intrinsic and extrinsic pathways as well as cell cycle arrest in colon and breast cancer cells.

Keywords: nickel complex, apoptosis, cytoskeletal rearrangement, colon cancer, breast cancer

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Authors: Deirdre Mc Grath, Joanne Reid

Abstract:

Background: Ovarian cancer is the leading cause of mortality among gynaecologic cancers in developed countries and the seventh most common cancer worldwide with nearly 240,000 women diagnosed each year. Although it is recognized engaging in exercise results in positive health care outcomes, women with ovarian cancer are reluctant to participate. No evidence currently exists focusing on how to successfully implement an exercise intervention program for patients with ovarian cancer, using a realist approach. There is a requirement for the implementation of exercise programmes within the oncology health care setting as engagement in such interventions has positive health care outcomes for women with ovarian cancer both during and following treatment. Aim: To co-design the implementation of an exercise intervention for women following treatment for ovarian cancer. Methods: This study is a realist evaluation using quantitative and qualitative methods of data collection and analysis. Realist evaluation is well-established within the health and social care setting and has in relation to this study enabled a flexible approach to investigate how to optimise implementation of an exercise intervention for this patient population. This single centre study incorporates three stages in order to identify the underlying contexts and mechanisms which lead to the successful implementation of an exercise intervention for women who have had treatment for ovarian cancer. Stage 1 - A realist literature review. Stage 2 -Co-design of the implementation of an exercise intervention with women following treatment for ovarian cancer, their carer’s, and health care professionals. Stage 3 –Implementation of an exercise intervention with women following treatment for ovarian cancer. Evaluation of the implementation of the intervention from the perspectives of the women who participated in the intervention, their informal carers, and health care professionals. The underlying program theory initially conceptualised before and during the realist review was developed further during the co-design stage. The evolving program theory in relation to how to successfully implement an exercise for these women is currently been refined and tested during the final stage of this realist evaluation which is the implementation and evaluation stage. Results: This realist evaluation highlights key issues in relation to the implementation of an exercise intervention within this patient population. The underlying contexts and mechanisms which influence recruitment, adherence, and retention rates of participants are identified. Conclusions: This study will inform future research on the implementation of exercise interventions for this patient population. It is anticipated that this intervention will be implemented into practice as part of standard care for this group of patients.

Keywords: ovarian cancer, exercise intervention, implementation, Co-design

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Authors: Nigatu Tadesse, Ying Liu, Juan Li, Hong Ming Liu

Abstract:

Gastric carcinogenesis is a lengthy process of histopathological transition from normal to atrophic gastritis (AG) to intestinal metaplasia (GIM), dysplasia toward gastric cancer (GC). The stage of GIM identified as precancerous lesions with resistance to H-pylori eradication and recurrence after endoscopic surgical resection therapies. GIM divided in to two morphologically distinct phenotypes such as complete GIM bearing intestinal type morphology whereas the incomplete type has colonic type morphology. The incomplete type GIM considered to be the greatest risk factor for the development of GC. Studies indicated the expression of the caudal type homeobox 2 (CDX2) gene is responsible for the development of complete GIM but its progressive downregulation from incomplete metaplasia toward advanced GC identified as the risk for IM progression and neoplastic transformation. The downregulation of CDX2 gene have promoted cell growth and proliferation in gastric and colon cancers and ascribed in chemo-treatment inefficacies. CDX2 downregulated through promoter region hypermethylation in which the methylation frequency positively correlated with the dietary history of the patients, suggesting the role of diet as methyl carbon donor sources such as methionine. However, the metabolism of exogenous methionine is yet unclear. Targeting exogenous methionine metabolism has become a promising approach to limits tumor cell growth, proliferation and progression and increase treatment outcome. This review article discusses molecular alterations that could shed light on the potential of exogenous methionine metabolisms, such as gut microbiota alteration as sources of methionine to host cells, metabolic pathway signaling via PI3K/AKt/mTORC1-c-MYC to rewire exogenous methionine and signature of increased gene methylation index, cell growth and proliferation in GIM, with insights to new treatment avenue via targeting methionine metabolism, and the need for future integrated studies on molecular alterations and metabolomics to uncover altered methionine metabolism and characterization of CDX2 methylation in gastric intestinal metaplasia for potential therapeutic exploitation.

Keywords: altered methionine metabolism, Intestinal metaplesia, CDX2 gene, gastric cancer

Procedia PDF Downloads 51

Authors: Deirdre Mc Grath, Joanne Reid

Abstract:

Background: Ovarian cancer is the leading cause of mortality among gynaecologic cancers in developed countries and the seventh most common cancer worldwide, with nearly 240,000 women diagnosed each year. Although it is recognized engaging in exercise results in positive health care outcomes, women with ovarian cancer are reluctant to participate. No evidence currently exists focusing on how to successfully implement an exercise intervention program for patients with ovarian cancer, using a realist approach. There is a requirement for the implementation of exercise programmes within the oncology health care setting as engagement in such interventions has positive health care outcomes for women with ovarian cancer both during and following treatment. Aim: To co-design the implementation of an exercise intervention for women following treatment for ovarian cancer. Methods: This study is a realist evaluation using quantitative and qualitative methods of data collection and analysis. Realist evaluation is well-established within the health and social care setting and has, in relation to this study, enabled a flexible approach to investigate how to optimise implementation of an exercise intervention for this patient population. This single centre study incorporates three stages in order to identify the underlying contexts and mechanisms which lead to the successful implementation of an exercise intervention for women who have had treatment for ovarian cancer. Stage 1 - A realist literature review. Stage 2 -Co-design of the implementation of an exercise intervention with women following treatment for ovarian cancer, their carer’s, and health care professionals. Stage 3 –Implementation of an exercise intervention with women following treatment for ovarian cancer. Evaluation of the implementation of the intervention from the perspectives of the women who participated in the intervention, their informal carers, and health care professionals. The underlying programme theory initially conceptualised before and during the realist review was developed further during the co-design stage. The evolving programme theory in relation to how to successfully implement an exercise for these women is currently been refined and tested during the final stage of this realist evaluation which is the implementation and evaluation stage. Results: This realist evaluation highlights key issues in relation to the implementation of an exercise intervention within this patient population. The underlying contexts and mechanisms which influence recruitment, adherence, and retention rates of participants are identified. Conclusions: This study will inform future research on the implementation of exercise interventions for this patient population. It is anticipated that this intervention will be implemented into practice as part of standard care for this group of patients.

Keywords: exercise, ovarian cancer, co-design, implementation

Procedia PDF Downloads 103

Authors: Mariola Głowacka

Abstract:

Aim: The aim of this study was to present the assessment of dyspnea and anxiety in seniors staying in the hospice in the context of the nurse's tasks. Materials and methods: The presented research was carried out at the "Hospicjum Płockie" Association of St. Urszula Ledóchowska in Płock, in a stationary ward, for adults. The research group consisted of 100 people, women, and men. In the study described in this paper, the method of diagnostic survey, the method of estimation and analysis of patient records were used, and the research tools were the numerical scale of the NRS assessment, the modified Borg scale to assess dyspnea, the Trait Anxiety scale to test the intensity of anxiety and the sociodemographic assessment of the respondent. Results: Among the patients, the greatest number were people without dyspnoea (38 people) and with average levels of dyspnoea (26 people). People with lung cancer had a higher level of breathlessness than people with other cancers. Half of the patients included in the study felt anxiety at a low level. On average, men had a higher level of anxiety than women. Conclusion: 1) Patients staying in the hospice require comprehensive nursing care due to the underlying disease, comorbidities, and a wide range of medications taken, which aggravate the feeling of dyspnea and anxiety. 2) The study showed that in patients staying in the hospice, the level of dyspnea was of varying severity. The greatest number of people were without dyspnea (38) and patients with a low level of dyspnea (34). There were 12 people experiencing an average level of dyspnea and a high level of dyspnea 15. 3) The main factor influencing the severity of dyspnea in patients was the location of cancer. There was no significant relationship between the intensity of dyspnea and the age, gender of the patient, and time from diagnosis. 4) The study showed that in patients staying in the hospice, the level of anxiety was of varying severity. Most people experience a low level of anxiety (51). There were 16 people with a high level of anxiety, while there were 33 people experiencing anxiety at an average level. 5) The patient's gender was the main factor influencing the increase in anxiety intensity. Men had higher levels of anxiety than women. There was no significant correlation between the intensity of anxiety and the age of the respondents, as well as the type of cancer and time since diagnosis. 6) The intensity of dyspnea depended on the type of cancer the subjects had. People with lung cancer had a higher level of breathlessness than those with breast cancer and bowel cancer. It was not found that the anxiety increased depending on the type of cancer and comorbidities of the examined person.

Keywords: cancer, shortness of breath, anxiety, senior, hospice

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Authors: U. K. Hulihalli, Shantveerayya

Abstract:

Buckwheat (Fagopyrum esculentum Moench) is an annual crop belongs to family Poligonaceae. The cultivated buckwheat species are notable for their exceptional nutritive values. It is an important source of carbohydrates, fibre, macro, and microelements such as K, Ca, Mg, Na and Mn, Zn, Se, and Cu. It also contains rutin, flavonoids, riboflavin, pyridoxine and many amino acids which have beneficial effects on human health, including lowering both blood lipid and sugar levels. Rutin, quercetin and some other polyphenols are potent carcinogens against colon and other cancers. Buckwheat has significant nutritive value and plenty of uses. Cultivation of buckwheat in Sothern part of India is very meager. Hence, a study was planned with an objective to know the performance of buckwheat genotypes to different planting geometries and fertility levels. The field experiment was conducted at Main Agriculture Research Station, University of Agriculture Sciences, Dharwad, India, during 2017 Kharif. The experiment was laid-out in split-plot design with three replications having three planting geometries as main plots, two genotypes as sub plots and three fertility levels as sub-sub plot treatments. The soil of the experimental site was vertisol. The standard procedures are followed to record the observations. The planting geometry of 30*10 cm was recorded significantly higher seed yield (893 kg/ha⁻¹), stover yield (1507 kg ha⁻¹), clusters plant⁻¹ (7.4), seeds clusters⁻¹ (7.9) and 1000 seed weight (26.1 g) as compared to 40*10 cm and 20*10 cm planting geometries. Between the genotypes, significantly higher seed yield (943 kg ha⁻¹) and harvest index (45.1) was observed with genotype IC-79147 as compared to PRB-1 genotype (687 kg ha⁻¹ and 34.2, respectively). However, the genotype PRB-1 recorded significantly higher stover yield (1344 kg ha⁻¹) as compared to genotype IC-79147 (1173 kg ha⁻¹). The genotype IC-79147 was recorded significantly higher clusters plant⁻¹ (7.1), seeds clusters⁻¹ (7.9) and 1000 seed weight (24.5 g) as compared PRB-1 (5.4, 5.8 and 22.3 g, respectively). Among the fertility levels tried, the fertility level of 60:30 NP kg ha⁻¹ recorded significantly higher seed yield (845 kg ha^-1) and stover yield (1359 kg ha⁻¹) as compared to 40:20 NP kg ha^-1 (808 and 1259 kg ha⁻¹ respectively) and 20:10 NP kg ha^-1 (793 and 1144 kg ha⁻¹ respectively). Within the treatment combinations, IC 79147 genotype having 30*10 cm planting geometry with 60:30 NP kg ha⁻¹ recorded significantly higher seed yield (1070 kg ha⁻¹), clusters plant⁻¹ (10.3), seeds clusters⁻¹ (9.9) and 1000 seed weight (27.3 g) compared to other treatment combinations.

Keywords: buckwheat, planting geometry, genotypes, fertility levels

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Authors: Adebisi Adunola Demehin, Wanlaya Thamnarak, Jaruwan Chatwichien, Chatchakorn Eurtivong, Kiattawee Choowongkomon, Somsak Ruchirawat, Nopporn Thasana

Abstract:

The epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein involved in cellular signalling processes and, its aberrant activity is crucial in the development of many cancers such as lung cancer. Selaginellaceae are fern allies that have long been used in Chinese traditional medicine to treat various cancer types, especially lung cancer. Biflavonoids, the major secondary metabolites in Selaginellaceae, have numerous pharmacological activities, including anti-cancer and anti-inflammatory. For instance, amentoflavone induces a cytotoxic effect in the human NSCLC cell line via the inhibition of PARP-1. However, to the best of our knowledge, there are no studies on biflavonoids as EGFR inhibitors. Thus, this study aims to investigate the EGFR inhibitory activities of biflavonoids isolated from Selaginella siamensis and Selaginella bryopteris. Amentoflavone, tetrahydroamentoflavone, sciadopitysin, robustaflavone, robustaflavone-4-methylether, delicaflavone, and chrysocauloflavone were isolated from the ethyl-acetate extract of the whole plants. The structures were determined using NMR spectroscopy and mass spectrometry. In vitro study was conducted to evaluate their cytotoxicity against A549, HEPG2, and T47D human cancer cell lines using the MTT assay. In addition, a target-based assay was performed to investigate their EGFR inhibitory activity using the kinase inhibition assay. Finally, a molecular docking study was conducted to predict the binding modes of the compounds. Robustaflavone-4-methylether and delicaflavone showed the best cytotoxic activity on all the cell lines with IC50 (µM) values of 18.9 ± 2.1 and 22.7 ± 3.3 on A549, respectively. Of these biflavonoids, delicaflavone showed the most potent EGFR inhibitory activity with an 84% relative inhibition at 0.02 nM using erlotinib as a positive control. Robustaflavone-4-methylether showed a 78% inhibition at 0.15 nM. The docking scores obtained from the molecular docking study correlated with the kinase inhibition assay. Robustaflavone-4-methylether and delicaflavone had a docking score of 72.0 and 86.5, respectively. The inhibitory activity of delicaflavone seemed to be linked with the C2”=C3” and 3-O-4”’ linkage pattern. Thus, this study suggests that the structural features of these compounds could serve as a basis for developing new EGFR-TK inhibitors.

Keywords: anticancer, biflavonoids, EGFR, molecular docking, Selaginellaceae

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Authors: Milton Ixquiac, Erick Montenegro, Francisco Reynoso, Matthew Schmidt, Thomas Mazur, Tianyu Zhao, Hiram Gay, Geoffrey Hugo, Lauren Henke, Jeff Michael Michalski, Angel Velarde, Vicky de Falla, Franky Reyes, Osmar Hernandez, Edgar Aparicio Ruiz, Baozhou Sun

Abstract:

Purpose: Radiotherapy departments in low- and middle-income countries (LMICs) like Guatemala have recently introduced intensity-modulated radiotherapy (IMRT). IMRT has become the standard of care in high-income countries (HIC) due to reduced toxicity and improved outcomes in some cancers. The purpose of this work is to show the agreement between the dosimetric results shown in the Dose Volume Histograms (DVH) to the objectives proposed in the adopted protocol. This is the initial experience with an O-ring Linac. Methods and Materials: An O-Linac Linac was installed at our clinic in Guatemala in 2019 and has been used to treat approximately 90 patients daily with IMRT. This Linac is a completely Image Guided Device since to deliver each radiotherapy session must take a Mega Voltage Cone Beam Computerized Tomography (MVCBCT). In each MVCBCT, the Linac deliver 9 UM, and they are taken into account while performing the planning. To start the standardization, the TG263 was employed in the nomenclature and adopted a hypofractionated protocol to treat ChestWall, including supraclavicular nodes achieving 40.05Gy in 15 fractions. The planning was developed using 4 semiarcs from 179-305 degrees. The planner must create optimization volumes for targets and Organs at Risk (OARs); the difficulty for the planner was the dose base due to the MVCBCT. To evaluate the planning modality, we used 30 chestwall cases. Results: The plans created manually achieve the protocol objectives. The protocol objectives are the same as the RTOG1005, and the DHV curves look clinically acceptable. Conclusions: Despite the O-ring Linac doesn´t have the capacity to obtain kv images, the cone beam CT was created using MV energy, the dose delivered by the daily image setup process still without affect the dosimetric quality of the plans, and the dose distribution is acceptable achieving the protocol objectives.

Keywords: hypofrationation, VMAT, chestwall, radiotherapy planning

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Authors: Laetitia Fourie

Abstract:

Dangerous myths and stereotypes contribute to the fact that persons living with albinism are amongst the most vulnerable groups in society. The prevalence of albinism varies around the world and the World Health Organization estimates that around 1 in 5000 people in Sub-Saharan Africa are affected by this genetic disorder. Persons who are living with the condition usually experience a lack of melanin in their skin, eyes and hair that results in possible physical impairments such as poor eyesight and skin cancers. Being affected by such disorders and consequently classified as an albino, give way for unequal treatment which ultimately requires safeguarding these persons against unfair discrimination - not only on the basis of their race and color (or lack thereof), but also on the basis of their disability. The Constitution of the Republic of South Africa provides that everyone is equal before the law and prohibits unfair discrimination on the grounds of race, color and disability. This right is given effect to by the Employment Equity Act, which strives to eliminate unfair discrimination on similar grounds within any employment policy or practice. An essential non-discrimination measure that can be implemented in the labor market to achieve equality is the duty of reasonable accommodation that rests upon employers. However, reasonable accommodation is only introduced as an affirmative action measure in order to provide equal employment opportunities to the identified designated groups who include black people (defined to include Indians, Chinese and Colored), women and people with disabilities. Even though this duty exists, South African law does not elaborate on the scope of the duty, except for a Disability Code, which does not hold the force of law. Furthermore, in respect of applying affirmative action measures to people with disabilities, the law does not elaborate on the meaning of disability. Considering that persons living with albinism will find it difficult to show that they are black or disabled in order to be acknowledged as part of the designated groups, their access to reasonable accommodation will be limited to a great extent. This paper will aim to illustrate to which extent South African law currently fails to implement its international obligations as a State Party to the Conventions of the United Nations, and how these failures should be corrected in order to serve the needs of all South Africans, including albinos.

Keywords: albinism, disability, equality, South Africa, United Nations

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Authors: Karen Boaz, C. R. Charan

Abstract:

Background: The infiltration of tumour stroma by eosinophils, Tumor-Associated Tissue Eosinophilia (TATE), is known to modulate the progression of Oral Squamous Cell Carcinoma (OSCC). Eosinophils have direct tumoricidal activity by release of cytotoxic proteins and indirectly they enhance permeability into tumor cells enabling penetration of tumoricidal cytokines. Also, eosinophils may promote tumor angiogenesis by production of several angiogenic factors. Identification of eosinophils in the inflammatory stroma has been proven to be an important prognosticator in cancers of mouth, oesophagus, larynx, pharynx, breast, lung, and intestine. Therefore, the study aimed to correlate TATE with clinical and histopathological variables, and blood eosinophil count to assess the role of TATE as a prognosticator in Oral Squamous Cell Carcinoma (OSCC). Methods: Seventy two biopsy-proven cases of OSCC formed the study cohort. Blood eosinophil counts and TNM stage were obtained from the medical records. Tissue sections (5µm thick) were stained with Haematoxylin and Eosin. The eosinophils were quantified at invasive tumour front (ITF) in 10HPF (40x magnification) with an ocular grid. Bryne’s grading of ITF was also performed. A subset of thirty cases was also assessed for association of TATE with recurrence, involvement of lymph nodes and surgical margins. Results: 1) No statistically significant correlation was found between TATE and TNM stage, blood eosinophil counts and most parameters of Bryne’s grading system. 2) Statistically significant relation of intense degree of TATE was associated with the absence of distant metastasis, increased lympho-plasmacytic response and increased survival (diseasefree and overall) of OSCC patients. 3) In the subset of 30 cases, tissue eosinophil counts were higher in cases with lymph node involvement, decreased survival, without margin involvement and in cases that did not recur. Conclusion: While the role of eosinophils in mediating immune responses seems ambiguous as eosinophils support cell-mediated tumour immunity in early stages while inhibiting the same in advanced stages, TATE may be used as a surrogate marker for determination of prognosis in oral squamous cell carcinoma.

Keywords: tumour-associated tissue eosinophilia, oral squamous cell carcinoma, prognosticator, tumoral immunity

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Authors: Iva Blazkova, Amitava Moulick, Vedran Milosavljevic, Pavel Kopel, Marketa Vaculovicova, Vojtech Adam, Rene Kizek

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Doxorubicin is one of the most commonly used and the most effective chemotherapeutic drugs. This antracycline drug isolated from the bacteria Streptomyces peuceticus var. caesius is sold under the trade name Adriamycin (hydroxydaunomycin, hydroxydaunorubicin). Doxorubicin is used in single therapy to treat hematological malignancies (blood cancers, leukaemia, lymphoma), many types of carcinoma (solid tumors) and soft tissue sarcomas. It has many serious side effects like nausea and vomiting, hair lost, myelosupression, oral mucositis, skin reactions and redness, but the most serious one is the cardiotoxicity. Because of the risk of heart attack and congestive heart failure, the total dose administered to patients has to be accurately monitored. With the aim to lower the side effects and to targeted delivery of doxorubicin into the tumor tissue, the different nanoparticles are studied. The drug can be bound on a surface of nanoparticle, encapsulated in the inner cavity, or incorporated into the structure of nanoparticle. Among others, carbon nanoparticles (graphene, carbon nanotubes, fullerenes) are highly studied. Besides the number of inorganic nanoparticles, a great potential exhibit also organic ones mainly lipid-based and polymeric nanoparticle. The aim of this work was to perform a toxicity study of free doxorubicin compared to doxorubicin conjugated with various nanotransporters. The effect of liposomes, fullerenes, graphene, and carbon nanotubes on the toxicity was analyzed. As a first step, the binding efficacy of between doxorubicin and the nanotransporter was determined. The highest efficacy was detected in case of liposomes (85% of applied drug was encapsulated) followed by graphene, carbon nanotubes and fullerenes. For the toxicological studies, the chicken embryos incubated under controlled conditions (37.5 °C, 45% rH, rotation every 2 hours) were used. In 7th developmental day of chicken embryos doxorubicin or doxorubicin-nanotransporter complex was applied on the chorioallantoic membrane of the eggs and the viability was analyzed every day till the 17th developmental day. Then the embryos were extracted from the shell and the distribution of doxorubicin in the body was analyzed by measurement of organs extracts using laser induce fluorescence detection. The chicken embryo mortality caused by free doxorubicin (30%) was significantly lowered by using the conjugation with nanomaterials. The highest accumulation of doxorubicin and doxorubicin nanotransporter complexes was observed in the liver tissue

Keywords: doxorubicin, chicken embryos, nanotransporters, toxicity

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Authors: Arpit Gite

Abstract:

Purpose: We have evaluated the role of Total Neoadjuvant Therapy in patients with Locally Advanced Rectal cancer by giving Chemoradiotherapy followed by consolidation chemotherapy (CRT-CNCT) and, after that, the strategy of wait and watch. Methods: In this prospective case series, we evaluated the results of three locally advanced Rectal cancers, two cases Stage II (cT3N0) and one case Stage III ( cT4aN2). All three patients' growth was 4-6 cm from the anal verge. We have treated with Chemoradiotherapy to dose of 45Gy/25 Fractions to elective nodal regions (Inguinal node in anal canal Involvement)and Primary and mesorectum (Phase I) followed by 14.4Gy/8 Fractions to Primary and Mesorectum(Phase II) to a total dose of 59.4Gy/33 Fractions with concurrent chemotherapy Tab Capecitabine 825mg/m2 PO BD with Radiation therapy. After 6 weeks of completion of Chemoradiotherapy, advised six cycles of consolidative chemotherapy, CAPEOX regimen, Oxaliplatin 130mg/m2 on day 1 and Capecitabine 1000mg/m2 PO BD on days 1-14 repeated on a 21-day cycle for a total of six cycles. The primary endpoint is Disease-free survival (DFS); the secondary endpoint is adverse events related to chemoradiotherapy. Radiation toxicity is assessed by RTOG criteria, and chemotherapy toxicity is assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. Results: After 6 weeks of completion of Chemoradiotherapy, we did PET-CT of all three patients; all three patients had a clinically complete response and we advised 6 cycles of consolidative chemotherapy. After completion of consolidative chemotherapy, again PET-CT and sigmoidoscopy, all three patients had complete response on PET-CT and no lesions on sigmoidoscopy and kept all three patients on wait and watch.2 patients had Grade 2 skin toxicities,1 patient had Grade 1 skin toxicity, .2 patients had Grade 2 lower GI toxicities, and 1 patient had Grade lower GI toxicity, both according to RTOG criteria. 3 patients had Grade 2 diarrhea due to capecitabine, and 1 patient had Grade 1 thrombocytopenia due to oxaliplatin assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. Conclusion: Sphincter Preservation is possible with this regimen in those who don’t want to opt for surgery or in case of low-lying rectal cancer.

Keywords: locally advanced rectal cancer, sphincter preservation, chemoradiotherapy, consolidative chemotherapy

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Authors: Nicholas Fletcher, Zachary Houston, Yongmei Zhao, Christopher Howard, Kristofer Thurecht

Abstract:

One promising approach to enhance nanomedicine therapeutic efficacy is to include a targeting agent, such as an antibody, to increase accumulation at the tumor site. However, the application of such targeted nanomedicines remains limited, in part due to difficulties involved with biomolecule conjugation to synthetic nanomaterials. One approach recently developed to overcome this has been to engineer bispecific antibodies (BsAbs) with dual specificity, whereby one portion binds to methoxy polyethyleneglycol (mPEG) epitopes present on synthetic nanomedicines, while the other binds to molecular disease markers of interest. In this way, noncovalent complexes of nanomedicine core, comprising a hyperbranched polymer (HBP) of primarily mPEG, decorated with targeting ligands are able to be produced by simple mixing. Further work in this area has now demonstrated such complexes targeting the breast cancer marker epidermal growth factor receptor (EGFR) to show enhanced binding to tumor cells both in vitro and in vivo. Indeed the enhanced accumulation at the tumor site resulted in improved therapeutic outcomes compared to untargeted nanomedicines and free chemotherapeutics. The current work on these BsAb-HBP conjugates focuses on further probing antibody-nanomaterial interactions and demonstrating broad applicability to a range of cancer types. Herein are reported BsAb-HBP materials targeted towards prostate-specific membrane antigen (PSMA) and study of their behavior in vivo using ⁸⁹Zr positron emission tomography (PET) in a dual-tumor prostate cancer xenograft model. In this model mice bearing both PSMA+ and PSMA- tumors allow for PET imaging to discriminate between nonspecific and targeted uptake in tumors, and better quantify the increased accumulation following BsAb conjugation. Also examined is the potential for formation of these targeted complexes in situ following injection of individual components? The aim of this approach being to avoid undesirable clearance of proteinaceous complexes upon injection limiting available therapeutic. Ultimately these results demonstrate BsAb functionalized nanomaterials as a powerful and versatile approach for producing targeted nanomedicines for a variety of cancers.

Keywords: bioengineering, cancer, nanomedicine, polymer chemistry

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Authors: Marissa Dallara, Amalia Ardeljan, Lexi Frankel, Nadia Obaed, Naureen Rashid, Omar Rashid

Abstract:

Human Cytomegalovirus (HCMV) is a ubiquitous virus that remains latent in approximately 60% of individuals in developed countries. Viral load is kept at a minimum due to a robust immune response that is produced in most individuals who remain asymptomatic. HCMV has been recently implicated in cancer research because it may impose oncomodulatory effects on tumor cells of which it infects, which could have an impact on the progression of cancer. HCMV has been implicated in increased pathogenicity of certain cancers such as gliomas, but in contrast, it can also exhibit anti-tumor activity. HCMV seropositivity has been recorded in tumor cells, but this may also have implications in decreased pathogenesis of certain forms of cancer such as leukemia as well as increased pathogenesis in others. This study aimed to investigate the correlation between cytomegalovirus and the incidence of breast cancer. Methods The data used in this project was extracted from a Health Insurance Portability and Accountability Act (HIPAA) compliant national database to analyze the patients infected versus patients not infection with cytomegalovirus using ICD-10, ICD-9 codes. Permission to utilize the database was given by Holy Cross Health, Fort Lauderdale, for the purpose of academic research. Data analysis was conducted using standard statistical methods. Results The query was analyzed for dates ranging from January 2010 to December 2019, which resulted in 14,309 patients in both the infected and control groups, respectively. The two groups were matched by age range and CCI score. The incidence of breast cancer was 1.642% and 235 patients in the cytomegalovirus group compared to 4.752% and 680 patients in the control group. The difference was statistically significant by a p-value of less than 2.2x 10^-16 with an odds ratio of 0.43 (0.4 to 0.48) with a 95% confidence interval. Investigation into the effects of HCMV treatment modalities, including Valganciclovir, Cidofovir, and Foscarnet, on breast cancer in both groups was conducted, but the numbers were insufficient to yield any statistically significant correlations. Conclusion This study demonstrates a statistically significant correlation between cytomegalovirus and a reduced incidence of breast cancer. If HCMV can exert anti-tumor effects on breast cancer and inhibit growth, it could potentially be used to formulate immunotherapy that targets various types of breast cancer. Further evaluation is warranted to assess the implications of cytomegalovirus in reducing the incidence of breast cancer.

Keywords: human cytomegalovirus, breast cancer, immunotherapy, anti-tumor

Procedia PDF Downloads 191