Search results for: poor outcome of delayed breast cancer treatment
Commenced in January 2007
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Paper Count: 13381

Search results for: poor outcome of delayed breast cancer treatment

12721 Application Difference between Cox and Logistic Regression Models

Authors: Idrissa Kayijuka

Abstract:

The logistic regression and Cox regression models (proportional hazard model) at present are being employed in the analysis of prospective epidemiologic research looking into risk factors in their application on chronic diseases. However, a theoretical relationship between the two models has been studied. By definition, Cox regression model also called Cox proportional hazard model is a procedure that is used in modeling data regarding time leading up to an event where censored cases exist. Whereas the Logistic regression model is mostly applicable in cases where the independent variables consist of numerical as well as nominal values while the resultant variable is binary (dichotomous). Arguments and findings of many researchers focused on the overview of Cox and Logistic regression models and their different applications in different areas. In this work, the analysis is done on secondary data whose source is SPSS exercise data on BREAST CANCER with a sample size of 1121 women where the main objective is to show the application difference between Cox regression model and logistic regression model based on factors that cause women to die due to breast cancer. Thus we did some analysis manually i.e. on lymph nodes status, and SPSS software helped to analyze the mentioned data. This study found out that there is an application difference between Cox and Logistic regression models which is Cox regression model is used if one wishes to analyze data which also include the follow-up time whereas Logistic regression model analyzes data without follow-up-time. Also, they have measurements of association which is different: hazard ratio and odds ratio for Cox and logistic regression models respectively. A similarity between the two models is that they are both applicable in the prediction of the upshot of a categorical variable i.e. a variable that can accommodate only a restricted number of categories. In conclusion, Cox regression model differs from logistic regression by assessing a rate instead of proportion. The two models can be applied in many other researches since they are suitable methods for analyzing data but the more recommended is the Cox, regression model.

Keywords: logistic regression model, Cox regression model, survival analysis, hazard ratio

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12720 Antineoplastic Effect of Tridham and Penta Galloyl Glucose in Experimental Mammary Carcinoma Bearing Rats

Authors: Karthick Dharmalingam, Stalin Ramakrishnan, Haseena Banu Hedayathullah Khan, Sachidanandanam Thiruvaiyaru Panchanadham, Shanthi Palanivelu

Abstract:

Background: Breast cancer is arising as the most dreadful cancer affecting women worldwide. Hence, there arises a need to search and test for new drugs. Herbal formulations used in Siddha preparations are proved to be effective against various types of cancer. They also offer advantage through synergistic amplification and diminish any possible adverse effects. Tridham (TD) is a herbal formulation prepared in our laboratory consisting of Terminalia chebula, Elaeocarpus ganitrus and Prosopis cineraria in a definite ratio and has been used for the treatment of mammary carcinoma. Objective: To study the restorative effect of Tridham and penta galloyl glucose (a component of TD) on DMBA induced mammary carcinoma in female Sprague Dawley rats. Materials and Methods: Rats were divided into seven groups of six animals each. Group I (Control) received corn oil. Group II– mammary carcinoma was induced by DMBA dissolved in corn oil single dose orally. Group III and Group IV were induced with DMBA and subsequently treated with Tridham and penta galloyl glucose, respectively for 48 days. Group V was treated with DMBA and subsequently with a standard drug, cyclophosphamide. Group VI and Group VII were given Tridham and penta galloyl glucose alone, respectively for 48 days. After the experimental period, the animals were sacrificed by cervical decapitation. The mammary gland tissue was excised and levels of antioxidants were determined by biochemical assay. p53 and PCNA expression were accessed using immunohistochemistry. Nrf-2, Cox-2 and caspase-3 protein expression were studied by Western Blotting analysis. p21, Bcl-2, Bax, Bad and caspase-8 gene expression were studied by RT-PCR. Results: Histopathological studies confirmed induction of mammary carcinoma in DMBA induced rats and treatment with TD and PGG resulted in regression of tumour. The levels of enzymic and non-enzymic antioxidants were decreased in DMBA induced rats when compared to control rats. The levels of cell cycle inhibitory markers and apoptotic markers were decreased in DMBA induced rats when compared to control rats. These parameters were restored to near normal levels on treatment with Tridham and PGG. Conclusion: The results of the present study indicate the antineoplastic effect of Tridham and PGG are exerted through the modulation of antioxidant status and expression of cell cycle regulatory markers as well as apoptotic markers. Acknowledgment: Financial assistance provided in the form of ICMR-SRF by Indian Council of Medical Research (ICMR), India is gratefully acknowledged here.

Keywords: antioxidants, Mammary carcinoma, pentaGalloyl glucose, Tridham

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12719 A Retrospective Study of Vaginal Stenosis Following Treatment of Cervical Cancers and the Effectiveness of Rehabilitation Interventions

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

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12718 Intensity of Dyspnea and Anxiety in Seniors in the Terminal Phase of the Disease

Authors: Mariola Głowacka

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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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12717 Advances in Natural Fiber Surface Treatment Methodologies for Upgradation in Properties of Their Reinforced Composites

Authors: G. L. Devnani, Shishir Sinha

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Natural fiber reinforced polymer composite is a very attractive area among the scientific community because of their low cost, eco-friendly and sustainable in nature. Among all advantages there are few issues which need to be addressed, those issues are the poor adhesion and compatibility between two opposite nature materials that is fiber and matrix and their relatively high water absorption. Therefore, natural fiber modifications are necessary to improve their adhesion with different matrices. Excellent properties could be achieved with the surface treatment of these natural fibers ultimately leads to property up-gradation of their reinforced composites with different polymer matrices. Lot of work is going on to improve the adhesion between reinforced fiber phase and polymer matrix phase to improve the properties of composites. Researchers have suggested various methods for natural fiber treatment like silane treatment, treatment with alkali, acetylation, acrylation, maleate coupling, etc. In this study a review is done on the different methods used for the surface treatment of natural fibers and what are the advance treatment methodologies for natural fiber surface treatment for property improvement of natural fiber reinforced polymer composites.

Keywords: composites, acetylation, natural fiber, surface treatment

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12716 Cloning and Expression of Azurin: A Protein Having Antitumor and Cell Penetrating Ability

Authors: Mohsina Akhter

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

Keywords: azurin, pseudomonas aeruginosa, cancer, therapeutics

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12715 Case Report of a Secretory Carcinoma of the Salivary Gland: Clinical Management Following High-Grade Transformation

Authors: Wissam Saliba, Mandy Nicholson

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Secretory carcinoma (SC) is a rare type of salivary gland cancer. It was first realized as a distinct type of malignancy in 2010and wasinitially termed “mammary analogue secretory carcinoma” because of similarities with secretory breast cancer. The name was later changed to SC. Most SCs originate in parotid glands, and most harbour a rare gene mutation: ETV6-NTRK3. This mutation is rare in common cancers and common in rare cancers; it is present in most secretory carcinomas. Disease outcomes for SC are usually described as favourable as many cases of SC are lowgrade (LG), and cancer growth is slow. In early stages, localized therapy is usually indicated (surgery and/or radiation). Despitea favourable prognosis, a sub-set of casescan be much more aggressive.These cases tend to be of high-grade(HG).HG casesare associated with a poorer prognosis.Management of such cases can be challenging due to limited evidence for effective systemic therapy options. This case report describes the clinical management of a 46-year-oldmale patient with a unique case of SC. He was initially diagnosed with a low/intermediate grade carcinoma of the left parotid gland in 2009; he was treated with surgery and adjuvant radiation. Surgical pathology favoured primary salivary adenocarcinoma, and 2 lymph nodes were positive for malignancy. SC was not yet realized as a distinct type of cancerat the time of diagnosis, and the pathology reportvalidated this gap by stating that the specimen lacked features of the defined types of salivary carcinoma.Slow-growing pulmonary nodules were identified in 2017. In 2020, approximately 11 years after the initial diagnosis, the patient presented with malignant pleural effusion. Pathology from a pleural biopsy was consistent with metastatic poorly differentiated cancer of likely parotid origin, likely mammary analogue secretory carcinoma. The specimen was sent for Next Generation Sequencing (NGS); ETV6-NTRK3 gene fusion was confirmed, and systemic therapy was initiated.One cycle ofcarboplatin/paclitaxel was given in June 2020. He was switched to Larotrectinib (NTRK inhibitor (NTRKi)) later that month. Larotrectinib continued for approximately 9 months, with discontinuation in March 2021 due to disease progression. A second-generation NTRKi (Selitrectinib) was accessed and prescribedthrough a single patient study. Selitrectinib was well tolerated. The patient experienced a complete radiological response within~4 months. Disease progression occurred once again in October 2021. Progression was slow, and Selitrectinib continuedwhile the medical team performed a thorough search for additional treatment options. In January 2022, a liver lesion biopsy was performed, and NGS showed an NTRKG623R solvent-front resistance mutation. Various treatment pathways were considered. The patient pursuedanother investigational NTRKi through a clinical trial, and Selitrectinib was discontinued in July 2022. Excellent performance status was maintained throughout the entire course of treatment.It can be concluded that NTRK inhibitors provided satisfactory treatment efficacy and tolerance for this patient with high-grade transformation and NTRK gene fusion cancer. In the future, more clinical research is needed on systemic treatment options for high-grade transformations in NTRK gene fusion SCs.

Keywords: secretory carcinoma, high-grade transformations, NTRK gene fusion, NTRK inhibitor

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12714 Targeting Methionine Metabolism In Gastric Cancer; Promising To Improve Chemosensetivity With Non-hetrogeneity

Authors: Nigatu Tadesse, Li Juan, Liuhong Ming

Abstract:

Gastric cancer (GC) is the fifth most common and fourth deadly cancer in the world with limited treatment options at late advanced stage in which surgical therapy is not recommended with chemotherapy remain as the mainstay of treatment. However, the occurrence of chemoresistance as well as intera-tumoral and inter-tumoral heterogeneity of response to targeted and immunotherapy underlined a clear unmet treatment need in gastroenterology. Several molecular and cellular alterations ascribed for chemo resistance in GC including cancer stem cells (CSC) and tumor microenvironment (TME) remodeling. Cancer cells including CSC bears higher metabolic demand and major changes in TME involves alterations of gut microbiota interacting with nutrients metabolism. Metabolic upregulation in lipids, carbohydrates, amino acids, fatty acids biosynthesis pathways identified as a common hall mark in GC. Metabolic addiction to methionine metabolism occurs in many cancer cells to promote the biosynthesis of S-Adenosylmethionine (SAM), a universal methyl donor molecule for high rate of transmethylation in GC and promote cell proliferation. Targeting methionine metabolism found to promotes chemo-sensitivity with treatment non-heterogeneity. Methionine restriction (MR) promoted the arrest of cell cycle at S/G2 phase and enhanced downregulation of GC cells resistance to apoptosis (including ferroptosis), which suggests the potential of synergy with chemotherapies acting at S-phase of the cell cycle as well as inducing cell apoptosis. Accumulated evidences showed both the biogenesis as well as intracellular metabolism of exogenous methionine could be safe and effective target for therapy either alone or in combination with chemotherapies. This review article provides an over view of the upregulation in methionine biosynthesis pathway and the molecular signaling through the PI3K/Akt/mTOR-c-MYC axis to promote metabolic reprograming through activating the expression of L-type aminoacid-1 (LAT1) transporter and overexpression of Methionine adenosyltransferase 2A(MAT2A) for intercellular metabolic conversion of exogenous methionine to SAM in GC, and the potential of targeting with novel therapeutic agents such as methioninase (METase), Methionine adenosyltransferase 2A (MAT2A), c-MYC, methyl like transferase 16 (METTL16) inhibitors that are currently under clinical trial development stages and future perspectives.

Keywords: gastric cancer, methionine metabolism, pi3k/akt/mtorc1-c-myc axis, gut microbiota, MAT2A, c-MYC, METTL16, methioninase

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12713 Evaluating the Diagnostic Accuracy of the ctDNA Methylation for Liver Cancer

Authors: Maomao Cao

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Objective: To test the performance of ctDNA methylation for the detection of liver cancer. Methods: A total of 1233 individuals have been recruited in 2017. 15 male and 15 female samples (including 10 cases of liver cancer) were randomly selected in the present study. CfDNA was extracted by MagPure Circulating DNA Maxi Kit. The concentration of cfDNA was obtained by Qubit™ dsDNA HS Assay Kit. A pre-constructed predictive model was used to analyze methylation data and to give a predictive score for each cfDNA sample. Individuals with a predictive score greater than or equal to 80 were classified as having liver cancer. CT tests were considered the gold standard. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for the diagnosis of liver cancer were calculated. Results: 9 patients were diagnosed with liver cancer according to the prediction model (with high sensitivity and threshold of 80 points), with scores of 99.2, 91.9, 96.6, 92.4, 91.3, 92.5, 96.8, 91.1, and 92.2, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value of ctDNA methylation for the diagnosis of liver cancer were 0.70, 0.90, 0.78, and 0.86, respectively. Conclusions: ctDNA methylation could be an acceptable diagnostic modality for the detection of liver cancer.

Keywords: liver cancer, ctDNA methylation, detection, diagnostic performance

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12712 Re-Evaluation of Functional Assessment of Anorexia/Cachexia Therapy (Appetite Scale) with Nutritional Intake of Cancer Patients

Authors: Amena Omer Syeda, Harita Shyam

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Background: Anorexia a common symptom among patients with prolonged illness leading to anorexia-cachexia syndrome with a prevalence rate of 70%. In order to provide effective health care and better response to treatment, appetite should be assessed on admission and then periodically for earlier nutrition intervention. Functional Assessment of Anorexia/Cachexia Therapy (FAACT) appetite scale is 12 questions, patient-rated, symptom specific measure for appetite, and distress from anorexia. It assigns a score ranging from 0 (worst response) to 4 (best response). Therefore, proposing a total score of ≤24 may be sufficient to make a diagnosis of anorexia. Objectives: To assess the FAACT scale by co-relating the scores with the Nutritional intake and BMI of Cancer Patients. Methods: The FAACT scores of 100 cancer in-patients receiving chemotherapy or radiation as treatment, their 24-hour calorie and protein intake and BMI were recorded. The data was then statistically analyzed. Results: The calorie and protein intake and FAACT scores both showed a significant positive co-relation (p<0.001), inferring that the patients with a FAACT score of ≤24 where not meeting their calorie as well as protein requirements, hence rightly categorizing them as anorexic. The co-relation between BMI and FAACT scores showed a weak co-relation and was not statistically significant (p > 0.05).The FAACT scale thus is not sensitive to distinguish patients being under-weight, normal weight or obese. Conclusion: The FAACT scale helps in providing better palliative and nutritional care as it correctly assessed anorexia /cachexia in cancer patients and co-related significantly with their nutrient intake.

Keywords: appetite, cachexia, cancer, malnutrition

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12711 Prevalence and Correlates of Anxiety and Depression among Family Carers of Cancer

Authors: Godfrey Katende, Lillian Nakimera

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The process of caregiving may cause emotional distress in form of anxiety and depression among family carers of cancer patients. Little is known about the prevalence anxiety and depression among family carers of cancer patients in Uganda. This cross-sectional study aimed to determine the prevalence of anxiety and depression among family carers of cancer patients and related factors associated with abnormal levels of anxiety and depression. A total of 119 family carers from Uganda Cancer Institute (UCI) were assessed by the Hospital Anxiety and Depression Scale (HADS) standardized questionnaire. The prevalence of anxiety and depression among family carers was high (45% and 26 % respectively); (2) abnormal levels of anxiety (ALA) and depression (ALD) was significantly associated with being a relative carer. Incorporating evidence based psychological therapies targeting family carers into usual care of cancer patients is imperative.

Keywords: anxiety, cancer, carer, cross-sectional design, depression, Uganda

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12710 Development of a Core Set of Clinical Indicators to Measure Quality of Care for Thyroid Cancer: A Modified-Delphi Approach

Authors: Liane J. Ioannou, Jonathan Serpell, Cino Bendinelli, David Walters, Jenny Gough, Dean Lisewski, Win Meyer-Rochow, Julie Miller, Duncan Topliss, Bill Fleming, Stephen Farrell, Andrew Kiu, James Kollias, Mark Sywak, Adam Aniss, Linda Fenton, Danielle Ghusn, Simon Harper, Aleksandra Popadich, Kate Stringer, David Watters, Susannah Ahern

Abstract:

BACKGROUND: There are significant variations in the management, treatment and outcomes of thyroid cancer, particularly in the role of: diagnostic investigation and pre-treatment scanning; optimal extent of surgery (total or hemi-thyroidectomy); use of active surveillance for small low-risk cancers; central lymph node dissections (therapeutic or prophylactic); outcomes following surgery (e.g. recurrent laryngeal nerve palsy, hypocalcaemia, hypoparathyroidism); post-surgical hormone, calcium and vitamin D therapy; and provision and dosage of radioactive iodine treatment. A proven strategy to reduce variations in the outcome and to improve survival is to measure and compare it using high-quality clinical registry data. Clinical registries provide the most effective means of collecting high-quality data and are a tool for quality improvement. Where they have been introduced at a state or national level, registries have become one of the most clinically valued tools for quality improvement. To benchmark clinical care, clinical quality registries require systematic measurement at predefined intervals and the capacity to report back information to participating clinical units. OBJECTIVE: The aim of this study was to develop a core set clinical indicators that enable measurement and reporting of quality of care for patients with thyroid cancer. We hypothesise that measuring clinical quality indicators, developed to identify differences in quality of care across sites, will reduce variation and improve patient outcomes and survival, thereby lessening costs and healthcare burden to the Australian community. METHOD: Preparatory work and scoping was conducted to identify existing high quality, clinical guidelines and best practice for thyroid cancer both nationally and internationally, as well as relevant literature. A bi-national panel was invited to participate in a modified Delphi process. Panelists were asked to rate each proposed indicator on a Likert scale of 1–9 in a three-round iterative process. RESULTS: A total of 236 potential quality indicators were identified. One hundred and ninety-two indicators were removed to reflect the data capture by the Australian and New Zealand Thyroid Cancer Registry (ANZTCR) (from diagnosis to 90-days post-surgery). The remaining 44 indicators were presented to the panelists for voting. A further 21 indicators were later added by the panelists bringing the total potential quality indicators to 65. Of these, 21 were considered the most important and feasible indicators to measure quality of care in thyroid cancer, of which 12 were recommended for inclusion in the final set. The consensus indicator set spans the spectrum of care, including: preoperative; surgery; surgical complications; staging and post-surgical treatment planning; and post-surgical treatment. CONCLUSIONS: This study provides a core set of quality indicators to measure quality of care in thyroid cancer. This indicator set can be applied as a tool for internal quality improvement, comparative quality reporting, public reporting and research. Inclusion of these quality indicators into monitoring databases such as clinical quality registries will enable opportunities for benchmarking and feedback on best practice care to clinicians involved in the management of thyroid cancer.

Keywords: clinical registry, Delphi survey, quality indicators, quality of care

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12709 Molecular Alterations Shed Light on Alteration of Methionine Metabolism in Gastric Intestinal Metaplesia; Insight for Treatment Approach

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

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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

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12708 Non-Canonical Beclin-1-Independent Autophagy and Apoptosis in Cell Death Induced by Rhus coriaria in Human Colon HT-29 Cancer Cells

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

Abstract:

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

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

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12707 Evaluation of Tumor Microenvironment Using Molecular Imaging

Authors: Fakhrosadat Sajjadian, Ramin Ghasemi Shayan

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

Keywords: molecular, imaging, TME, medicine

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12706 Formulation and Evaluation of Silver Nanoparticles as Drug Carrier for Cancer Therapy

Authors: Abdelhadi Adam Salih Denei

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

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

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12705 Xiaflex (Collagenase) Impact on the Management of Dupuytren's Disease: Making the Case for Treatment in a Public Healthcare System

Authors: Anthony Barker, Roland Jiang

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Dupuytren’s contractures are a debilitating condition affecting the palmar fascia of the hand reducing its function. This case series looks at the minimally-invasive technique of Xiaflex injections and the outcome in a public health setting. 15 patients undertook collagenase injection (Xiaflex, C. histolyticum) injection over the period from September 2015 to May 2017 at Fairfield Hospital, NSW. Their reported outcome post injection and in follow-up was recorded as well as their satisfaction and likelihood to request the procedure in the future. Other treatment modalities include percutaneous needle aponeurotomy, limited palmar fasciotomy, and palmar fasciectomy. A literature review of cost-effectiveness was performed to compare Xiaflex suitability for waitlist reduction in a public setting given average waiting times in the public setting extend past 365 days.

Keywords: Dupuytrens Disease, xiaflex, collagenase, plastic surgery

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12704 Random Variation of Treated Volumes in Fractionated 2D Image Based HDR Brachytherapy for Cervical Cancer

Authors: R. Tudugala, B. M. A. I. Balasooriya, W. M. Ediri Arachchi, R. W. M. W. K. Rathnayake, T. D. Premaratna

Abstract:

Brachytherapy involves placing a source of radiation near the cancer site which gives promising prognosis for cervical cancer treatments. The purpose of this study was to evaluate the effect of random variation of treated volumes in between fractions in the 2D image based fractionated high dose rate brachytherapy for cervical cancer at National Cancer Institute Maharagama, Sri Lanka. Dose plans were analyzed for 150 cervical cancer patients with orthogonal radiographs (2D) based brachytherapy. ICRU treated volumes was modeled by translating the applicators with the help of “Multisource HDR plus software”. The difference of treated volumes with respect to the applicator geometry was analyzed by using SPSS 18 software; to derived patient population based estimates of delivered treated volumes relative to ideally treated volumes. Packing was evaluated according to bladder dose, rectum dose and geometry of the dose distribution by three consultant radiation oncologist. The difference of treated volumes depends on types of the applicators, which was used in fractionated brachytherapy. The means of the “Difference of Treated Volume” (DTV) for “Evenly activated tandem (ET)” length” group was ((X_1)) -0.48 cm3 and ((X_2)) 11.85 cm3 for “Unevenly activated tandem length (UET) group. The range of the DTV for ET group was 35.80 cm3 whereas UET group 104.80 cm3. One sample T test was performed to compare the DTV with “Ideal treatment volume difference (0.00cm3)”. It is evident that P value was 0.732 for ET group and for UET it was 0.00 moreover independent two sample T test was performed to compare ET and UET groups and calculated P value was 0.005. Packing was evaluated under three categories 59.38% used “Convenient Packing Technique”, 33.33% used “Fairly Packing Technique” and 7.29% used “Not Convenient Packing” in their fractionated brachytherapy treatments. Random variation of treated volume in ET group is much lower than UET group and there is a significant difference (p<0.05) in between ET and UET groups which affects the dose distribution of the treatment. Furthermore, it can be concluded nearly 92.71% patient’s packing were used acceptable packing technique at NCIM, Sri Lanka.

Keywords: brachytherapy, cervical cancer, high dose rate, tandem, treated volumes

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12703 Increased Retention of Nanoparticle by Small Molecule Inhibitor in Cancer Cells

Authors: Neha Singh

Abstract:

Background: Nowadays, the nanoparticle is gaining unexceptional attention in targeted drug delivery. But before proceeding to this episode of accomplishment, the journey and closure of these nanoparticles inside the cells should be disentangle. Being foreign for the cells, nanoparticles will easily getcleared off without any effective outcome. As the cancer cells withhold these nanoparticles for a longer period of time, more will be the drug’s effect. Chlorpromazine is a cationic amphiphilic drug which is believed to inhibit clathrin-coated pit formation by a reversible translocation of clathrin and its adapter proteins from the plasma membrane to intracellular vesicles. Chlorpromazine has a role in increasing the retention of nanoparticles in cancer cells. The mechanism of action how this small molecule increases the retention of nanoparticles is still uncovered. Method: Polymeric nanoparticle (PLGA) with Cyanine3.5 dye were synthesized by solvent evaporation method and characterized for size and zeta potential. FTIR was also done. Pulse and chase studies with and without inhibitor were done to check the retention of nanoparticle using fluorescence microscopy. Mean fluorescence intensity was measured by ImageJ software. Results: Increased retention of nanoparticle with inhibitor was observed in both pulse and chase studies. Conclusion: Our results demonstrate that by repurposing these small molecule inhibitor, we can increase the retention of nanoparticle at the targeted site.

Keywords: nanoparticle, endocytosis, clathrin inhibitor, cancer cell

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12702 Effect of Addition Rate of Expansive Additive on Autogenous Shrinkage and Delayed Expansion of Ultra-High Strength Mortar

Authors: Yulu Zhang, Atushi Teramoto, Taka-Aki Ohkubo

Abstract:

In this study, the effect of expansive additives on autogenous shrinkage and delayed expansion of ultra-high strength mortar was explored. The specimens made for the study were composed of ultra-high strength mortar, which was mixed with ettringite-lime composite type expansive additive. Two series of experiments were conducted with the specimens. The experimental results confirmed that the autogenous shrinkage of specimens was effectively decreased by increasing the proportion of the expansive additive. On the other hand, for the specimens, which had 7% expansive additive, and were cured for seven days at a constant temperature of 20°C, and then cured for a long time in either in an underwater, moist (Relative humidity: 100%) or dry air (Relative humidity: 60%) environment, excessively large expansion strain occurred. Specifically, typical turtle shell-like swelling expansion cracks were confirmed in the specimens that underwent long-term curing in an underwater and moist environment. According to the result of hydration analysis, the formation of expansive substances, calcium hydroxide and alumina, ferric oxide, tri-sulfate contribute to the occurrence of delayed expansion.

Keywords: ultra-high strength mortar, expansive additive, autogenous shrinkage, delayed expansion

Procedia PDF Downloads 232
12701 Involvement of BCRP/ABCG2 in Protective Mechanisms of Resveratrol against Methotrexate-Induced Renal Damage in Rats

Authors: Mohamed A. Morsy, Azza A. El-Sheikh, Abdulla Y. Al-Taher

Abstract:

Resveratrol (RES) is a well-known polyphenol antioxidant. We have previously shown that testicular protective effect of RES against the anticancer drug methotrexate (MTX)-induced toxicity involves transporter-mediated mechanisms. Here, we investigated the effect of RES on MTX-induced nephrotoxicity. Rats were administered RES (10 mg/kg/day) for 8 days, with or without a single MTX dose (20 mg/kg i.p.) at day 4 of the experiment. MTX induced nephrotoxicity evident by significantly increase in serum blood urea nitrogen and creatinine compared to control, as well as distortion of kidney microscopic structure. MTX also significantly increased renal nitric oxide level, with induction of inducible nitric oxide synthase expression. MTX also significantly up-regulated fas ligand and caspase 3. Administering RES prior to MTX significantly improved kidney function and microscopic picture, as well as significantly decreased nitrosative and apoptotic markers compared to MTX alone. RES, but not MTX, caused significant increase in expression of breast cancer resistance protein (BCRP), an apical efflux renal transporter that participates in urinary elimination of both MTX and RES. Interestingly, concomitant MTX and RES caused further up-regulation of renal Bcrp compared to RES alone. Using Human BCRP ATPase assay, both RES and MTX exhibited dose-dependent increase in ATPase activity, with Km values of 0.52 ± 0.03 and 30.9 ± 4.2 µM, respectively. Furthermore, combined RES and MTX caused ATPase activity which was significantly less than maximum ATPase activity attained by the positive control; sulfasalazine (12.5 µM). In conclusion, RES exerted nephro-protection against MTX-induced toxicity through anti-nitrosative and anti-apoptotic effects, as well as via up-regulation of renal Bcrp.

Keywords: methotrexate, resveratrol, nephrotoxicity, breast cancer resistance protein

Procedia PDF Downloads 285
12700 Development of an Interactive and Robust Image Analysis and Diagnostic Tool in R for Early Detection of Cervical Cancer

Authors: Kumar Dron Shrivastav, Ankan Mukherjee Das, Arti Taneja, Harpreet Singh, Priya Ranjan, Rajiv Janardhanan

Abstract:

Cervical cancer is one of the most common cancer among women worldwide which can be cured if detected early. Manual pathology which is typically utilized at present has many limitations. The current gold standard for cervical cancer diagnosis is exhaustive and time-consuming because it relies heavily on the subjective knowledge of the oncopathologists which leads to mis-diagnosis and missed diagnosis resulting false negative and false positive. To reduce time and complexities associated with early diagnosis, we require an interactive diagnostic tool for early detection particularly in developing countries where cervical cancer incidence and related mortality is high. Incorporation of digital pathology in place of manual pathology for cervical cancer screening and diagnosis can increase the precision and strongly reduce the chances of error in a time-specific manner. Thus, we propose a robust and interactive cervical cancer image analysis and diagnostic tool, which can categorically process both histopatholgical and cytopathological images to identify abnormal cells in the least amount of time and settings with minimum resources. Furthermore, incorporation of a set of specific parameters that are typically referred to for identification of abnormal cells with the help of open source software -’R’ is one of the major highlights of the tool. The software has the ability to automatically identify and quantify the morphological features, color intensity, sensitivity and other parameters digitally to differentiate abnormal from normal cells, which may improve and accelerate screening and early diagnosis, ultimately leading to timely treatment of cervical cancer.

Keywords: cervical cancer, early detection, digital Pathology, screening

Procedia PDF Downloads 170
12699 Identification of Potential Small Molecule Inhibitors Against β-hCG for Cancer Therapy: An In-Silico Study

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

Abstract:

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.

Procedia PDF Downloads 99
12698 Effect of Radiotherapy/Chemotherapy Protocol on the Gut Microbiome in Pediatric Cancer Patients

Authors: Nourhan G. Sahly, Ahmed Moustafa, Mohamed S. Zaghloul, Tamer Z. Salem

Abstract:

The gut microbiome plays important roles in the human body that includes but not limited to digestion, immunity, homeostasis and response to some drugs such as chemotherapy and immunotherapy. Its role has also been linked to radiotherapy and associated gastrointestinal injuries, where the microbial dysbiosis could be the driving force for dose determination or the complete suspension of the treatment protocol. Linking the gut microbiota alterations to different cancer treatment protocols is not easy especially in humans. However, enormous effort was exerted to understand this complex relationship. In the current study, we described the gut microbiota dysbiosis in pediatric sarcoma patients, in the pelvic region, with regards to radiotherapy and antibiotics. Fecal samples were collected as a source of microbial DNA for which the gene encoding for V3-V5 regions of 16S rRNA was sequenced. Two of the three patients understudy had experienced an increase in alpha diversity post exposure to 50.4 Gy. Although phylum Firmicutes overall relative abundance has generally decreased, six of its taxa increased in all patients. Our results may indicate the possibility of radiosensitivity or enrichment of the antibiotic resistance of the elevated taxa. Further studies are needed to describe the extent of radiosensitivity with regards to antibiotic resistance.

Keywords: combined radiotherapy and chemotherapy, gut microbiome, pediatric cancer, radiosensitivity

Procedia PDF Downloads 146
12697 Texture Analysis of Grayscale Co-Occurrence Matrix on Mammographic Indexed Image

Authors: S. Sushma, S. Balasubramanian, K. C. Latha

Abstract:

The mammographic image of breast cancer compressed and synthesized to get co-efficient values which will be converted (5x5) matrix to get ROI image where we get the highest value of effected region and with the same ideology the technique has been extended to differentiate between Calcification and normal cell image using mean value derived from 5x5 matrix values

Keywords: texture analysis, mammographic image, partitioned gray scale co-oocurance matrix, co-efficient

Procedia PDF Downloads 526
12696 Biological Significance of Long Intergenic Noncoding RNA LINC00273 in Lung Cancer Cell Metastasis

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

Abstract:

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

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

Procedia PDF Downloads 149
12695 Role of Imaging in Predicting the Receptor Positivity Status in Lung Adenocarcinoma: A Chapter in Radiogenomics

Authors: Sonal Sethi, Mukesh Yadav, Abhimanyu Gupta

Abstract:

The upcoming field of radiogenomics has the potential to upgrade the role of imaging in lung cancer management by noninvasive characterization of tumor histology and genetic microenvironment. Receptor positivity like epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) genotyping are critical in lung adenocarcinoma for treatment. As conventional identification of receptor positivity is an invasive procedure, we analyzed the features on non-invasive computed tomography (CT), which predicts the receptor positivity in lung adenocarcinoma. Retrospectively, we did a comprehensive study from 77 proven lung adenocarcinoma patients with CT images, EGFR and ALK receptor genotyping, and clinical information. Total 22/77 patients were receptor-positive (15 had only EGFR mutation, 6 had ALK mutation, and 1 had both EGFR and ALK mutation). Various morphological characteristics and metastatic distribution on CT were analyzed along with the clinical information. Univariate and multivariable logistic regression analyses were used. On multivariable logistic regression analysis, we found spiculated margin, lymphangitic spread, air bronchogram, pleural effusion, and distant metastasis had a significant predictive value for receptor mutation status. On univariate analysis, air bronchogram and pleural effusion had significant individual predictive value. Conclusions: Receptor positive lung cancer has characteristic imaging features compared with nonreceptor positive lung adenocarcinoma. Since CT is routinely used in lung cancer diagnosis, we can predict the receptor positivity by a noninvasive technique and would follow a more aggressive algorithm for evaluation of distant metastases as well as for the treatment.

Keywords: lung cancer, multidisciplinary cancer care, oncologic imaging, radiobiology

Procedia PDF Downloads 126
12694 Biophysical Modeling of Anisotropic Brain Tumor Growth

Authors: Mutaz Dwairy

Abstract:

Solid tumors have high interstitial fluid pressure (IFP), high mechanical stress, and low oxygen levels. Solid stresses may induce apoptosis, stimulate the invasiveness and metastasis of cancer cells, and lower their proliferation rate, while oxygen concentration may affect the response of cancer cells to treatment. Although tumors grow in a nonhomogeneous environment, many existing theoretical models assume homogeneous growth and tissue has uniform mechanical properties. For example, the brain consists of three primary materials: white matter, gray matter, and cerebrospinal fluid (CSF). Therefore, tissue inhomogeneity should be considered in the analysis. This study established a physical model based on convection-diffusion equations and continuum mechanics principles. The model considers the geometrical inhomogeneity of the brain by including the three different matters in the analysis: white matter, gray matter, and CSF. The model also considers fluid-solid interaction and explicitly describes the effect of mechanical factors, e.g., solid stresses and IFP, chemical factors, e.g., oxygen concentration, and biological factors, e.g., cancer cell concentration, on growing tumors. In this article, we applied the model on a brain tumor positioned within the white matter, considering the brain inhomogeneity to estimate solid stresses, IFP, the cancer cell concentration, oxygen concentration, and the deformation of the tissues within the neoplasm and the surrounding. Tumor size was estimated at different time points. This model might be clinically crucial for cancer detection and treatment planning by measuring mechanical stresses, IFP, and oxygen levels in the tissue.

Keywords: biomechanical model, interstitial fluid pressure, solid stress, tumor microenvironment

Procedia PDF Downloads 37
12693 Improvement of Visual Acuity in Patient Undergoing Occlusion Therapy

Authors: Rajib Husain, Mezbah Uddin, Mohammad Shamsal Islam, Rabeya Siddiquee

Abstract:

Purpose: To determine the improvement of visual acuity in patients undergoing occlusion therapy. Methods: This was a prospective hospital-based study of newly diagnosed of amblyopia seen at the pediatric clinic of Chittagong Eye Infirmary & Training Complex. There were 32 refractive amblyopia subjects were examined & questionnaire was piloted. Included were all patients diagnosed with refractive amblyopia between 5 to 8 years, without previous amblyopia treatment, and whose parents were interested to participate in the study. Patients diagnosed with strabismic amblyopia were excluded. Patients were first corrected with the best correction for a month. When the VA in the amblyopic eye did not improve over a month, then occlusion treatment was started. Occlusion was done daily for 6-8 h together with vision therapy. The occlusion was carried out for three months. Results: Out of study 32 children, 31 of them have a good compliance of amblyopic treatment whereas one child has poor compliance. About 6% Children have amblyopia from Myopia, 7% Hyperopia, 32% from myopic astigmatism, 42% from hyperopic astigmatism and 13% have mixed astigmatism. The mean and Standard deviation of present average VA was 0.452±0.275 Log MAR and after an intervention of amblyopia therapy with vision therapy mean and Standard deviation VA was 0.155±0.157 Log MAR. Out of total respondent 21.85% have BCVA in range from (0-.2) log MAR, 37.5% have BCVA in range from (0.22-0.5) log MAR, 35.95% have in range from (0.52-0.8) log MAR, 4.7% have in range from (0.82-1) log MAR and after intervention of occlusion therapy with vision therapy 76.6% have VA in range from (0-.2) log MAR, 21.85% have VA in range from (0.22-0.5) log MAR, 1.5% have in range from (0.52-0.8) log MAR. Conclusion: Amblyopia is a most important factor in pediatric age group because it can lead to visual impairment. Thus, this study concludes that occlusion therapy with vision therapy is probably one of the best treatment methods for amblyopic patients (age 5-8 years), and compliance and age were the most critical factor predicting a successful outcome.

Keywords: amblyopia, occlusion therapy, vision therapy, eccentric fixation, visuoscopy

Procedia PDF Downloads 499
12692 The Effect of Endurance Training and Taxol Consumption on Cyclooxygenase-2 and Prostaglandin E2 Levels in the Liver Tissue of Mice with Cervical Cancer

Authors: Alireza Barari, Maryam Firozi-Niyaki, Maryam Kamarlouei

Abstract:

Background: Herbs have a strong anti-cancer effect. Also, exercise is one of several lifestyle factors known to lower the risk of developing cancer. The aim of this study was to investigate the effect of endurance training and taxol on cyclooxygenase-2 and prostaglandin E2 in the liver tissue of mice with cervical cancer. Materials and Methods: In this experimental study, 35 female C57 mice were randomly divided into 5 groups (n=7 in each group): control (healthy), control (cancer), complement (cancer), training-supplementary (cancer) and training (cancer). The implantation of cancerous tumors was performed under the skin of the upper pelvis. The training group completed the endurance training protocol, which included 3 sessions per week, 50 minutes per session, at a speed of 14-18 m/s for six weeks. A dose of 60 mg/kg/day of pure taxol was injected intra peritoneally. The dependent variables of this study were measured 24 hours after the last training session by ELISA. Results: The results showed that the use of taxol and endurance training reduced the levels of cyclooxygenase-2 and prostaglandin E2 in the liver tissues of C57 mice with cervical cancer. Conclusion: Induction of the cancerous tissue in mice with cervical cancer increases the levels of cyclooxygenase-2 and prostaglandin E2 and endurance training along with taxol may reduce these levels.

Keywords: cervical cancer, taxol, endurance training, cyclooxygenase-2, prostaglandin E2

Procedia PDF Downloads 228