Search results for: TB and lung cancer
Commenced in January 2007
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Edition: International
Paper Count: 2427

Search results for: TB and lung cancer

1497 Consolidated Predictive Model of the Natural History of Breast Cancer Considering Primary Tumor and Secondary Distant Metastases Growth

Authors: Ella Tyuryumina, Alexey Neznanov

Abstract:

This study is an attempt to obtain reliable data on the natural history of breast cancer growth. We analyze the opportunities for using classical mathematical models (exponential and logistic tumor growth models, Gompertz and von Bertalanffy tumor growth models) to try to describe growth of the primary tumor and the secondary distant metastases of human breast cancer. The research aim is to improve predicting accuracy of breast cancer progression using an original mathematical model referred to CoMPaS and corresponding software. We are interested in: 1) modelling the whole natural history of the primary tumor and the secondary distant metastases; 2) developing adequate and precise CoMPaS which reflects relations between the primary tumor and the secondary distant metastases; 3) analyzing the CoMPaS scope of application; 4) implementing the model as a software tool. The foundation of the CoMPaS is the exponential tumor growth model, which is described by determinate nonlinear and linear equations. The CoMPaS corresponds to TNM classification. It allows to calculate different growth periods of the primary tumor and the secondary distant metastases: 1) ‘non-visible period’ for the primary tumor; 2) ‘non-visible period’ for the secondary distant metastases; 3) ‘visible period’ for the secondary distant metastases. The CoMPaS is validated on clinical data of 10-years and 15-years survival depending on the tumor stage and diameter of the primary tumor. The new predictive tool: 1) is a solid foundation to develop future studies of breast cancer growth models; 2) does not require any expensive diagnostic tests; 3) is the first predictor which makes forecast using only current patient data, the others are based on the additional statistical data. The CoMPaS model and predictive software: a) fit to clinical trials data; b) detect different growth periods of the primary tumor and the secondary distant metastases; c) make forecast of the period of the secondary distant metastases appearance; d) have higher average prediction accuracy than the other tools; e) can improve forecasts on survival of breast cancer and facilitate optimization of diagnostic tests. The following are calculated by CoMPaS: the number of doublings for ‘non-visible’ and ‘visible’ growth period of the secondary distant metastases; tumor volume doubling time (days) for ‘non-visible’ and ‘visible’ growth period of the secondary distant metastases. The CoMPaS enables, for the first time, to predict ‘whole natural history’ of the primary tumor and the secondary distant metastases growth on each stage (pT1, pT2, pT3, pT4) relying only on the primary tumor sizes. Summarizing: a) CoMPaS describes correctly the primary tumor growth of IA, IIA, IIB, IIIB (T1-4N0M0) stages without metastases in lymph nodes (N0); b) facilitates the understanding of the appearance period and inception of the secondary distant metastases.

Keywords: breast cancer, exponential growth model, mathematical model, metastases in lymph nodes, primary tumor, survival

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1496 Incidence of Vulval, Vaginal and Cervical Disease in Rapid Access Clinic in a London Tertiary Hospital Setting

Authors: Kieren Wilson, Gulnaz Majeed

Abstract:

NHS constitution gives rights to the patient with suspected cancer to be seen by a cancer specialist within 2 weeks of referral. Guys and St Thomas Hospital (GSTT) is one of the largest cancer centres in London. NICE guidelines have provided guidance for health professionals to refer patients appropriately to RAC. In GSTT suspected gynae cancer referrals are mostly by NHS e-Referral Service with some fax, emails as well as paper referrals. The objective of this study was to evaluate compliance with 2-week referral pathway with emphasis on one stop diagnostic service with supporting efficient pathways. A prospective evaluation over 3 months (1 Jan 2017 to 31 Mar 2017) was undertaken. There were 26 clinics, 761 patients were booked in the clinics with a DNA rate of 13% (n=101) hence 606 patients were seen. Majority of referrals were for post menopausal bleeding (PMB) 25% (n=194) followed by cervical, vaginal, vulval reasons 23% (n=179) (abnormal cytology excluded as patients directly referred to colposcopy unit in GSTT), ovarian 7% (n=54) and endometrial 5% (n=41). Women with new or previous established diagnosis of cancer were 24, cervical (n=17), vulva (n=6) and vagina (n=1). Multifocal preinvasive disease vulva (VIN), vagina (VAIN) and cervix (CIN) was confirmed in twenty-six patients 4% (high prevalence in HIV patients). Majority of cervical referrals: PCB (n=14), cervical erosion (n=7), polyps (n=9) and cervical cyst were benign. However, two women with PMB had cervical cancer. Only 2 out of 13 referrals with vaginal concerns had VAIN. One case with non-cervical glandular cytology was confirmed to have endometrial cancer. One stop service based on the diagnostic support of ultrasound, colposcopy and hysteroscopy was achieved in 54% (n=359). Patients were discharged to GP, benign gynaecology, endometriosis, combined vulval/dermatology clinic or gynae oncology. 33% (n=202) required a second visit, 12% (n=70) third visit, 3% (n=19) fourth visit, 1% (n=4) fifth visit and 1% (n=6) sixth visit. Main reasons for follow ups were the unavailability of diagnostic slots, patient choice, need for interpreters, the discussion following gynae MDM review for triage to benign gynae, delay in availability of diagnostic results like histology/MRI/CT. Recommendations following this study are multi disciplinary review of pathways with the availability of additional diagnostic procedure slots to aim for one stop service. Furthermore, establishment of virtual and telephone consultations to reduce follow ups.

Keywords: multifocal disease, post menopausal bleeding, preinvasive disease, rapid access clinic

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1495 Induction of Cytotoxicity and Apoptosis in Ovarian Cancer Cell Line (CAOV-3) by an Isoquinoline Alkaloid Isolated from Enicosanthellum pulchrum (King) Heusden

Authors: Noraziah Nordin, Najihah Mohd Hashim, Nazia Abdul Majid, Mashitoh Abdul Rahman, Hamed Karimian, Hapipah Mohd Ali

Abstract:

Enicosanthellum pulchrum belongs to family Annonaceae is also known as family of 'mempisang' in Malaysia. Liriodenine was isolated by prep-HPLC method. This method was first technique used for the isolation of this compound. The structure of the liriodenine was elucidated by 1D and 2D spectroscopy techniques. Liriodenine was tested on ovarian cancer cells line (CAOV-3) for MTT, AO/PI and cytotoxicity 3 assays. The MTT assay was performed to determine the cytotoxicity effect of lirodenine on CAOV-3 cells. The morphological changes on CAOV-3 cells were observed by AO/PI assay for the early and late stage of apoptosis, as well as necrosis. Meanwhile, the measurement of cell loss, nuclear morphology, DNA content, cell membrane permeability, mitochondrial membrane potential changes and cytochrome c release from mitochondria were detected through cytotoxicity 3 assay. The IC50 results showed liriodenine inhibits the growth of CAOV-3 cells after 24 h of treatment at 10.25 ± 1.06 µg/mL. After 48 and 72 h of treatments, the IC50 values were decreased to 7.65 ± 0:07 and 6.35 ± 1.62 µg/mL, respectively. The morphology changes can be seen on CAOV-3 with a production of cell membrane blebbing, cromatin condensation and apoptotic bodies with increasing time of treatment from 24 to 72 h. Evaluation of cytotoxicity 3 on CAOV-3 cells after treated with liriodenine, resulting loss of mitochondrial membrane potential and release of cytochrome c from mitochondria. The results demonstrated the capability of liriodenine as a promising anticancer agent, particularly on human ovarian cancer.

Keywords: Enicosanthellum pulchrum, ovarian cancer, apoptosis, cytotoxicity

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1494 Comprehensive Analysis of RNA m5C Regulator ALYREF as a Suppressive Factor of Anti-tumor Immune and a Potential Tumor Prognostic Marker in Pan-Cancer

Authors: Yujie Yuan, Yiyang Fan, Hong Fan

Abstract:

Objective: The RNA methylation recognition protein Aly/REF export factor (ALYREF) is considered one type of “reader” protein acting as a recognition protein of m5C, has been reported involved in several biological progresses including cancer initiation and progression. 5-methylcytosine (m5C) is a conserved and prevalent RNA modification in all species, as accumulating evidence suggests its role in the promotion of tumorigenesis. It has been claimed that ALYREF mediates nuclear export of mRNA with m5C modification and regulates biological effects of cancer cells. However, the systematical regulatory pathways of ALYREF in cancer tissues have not been clarified, yet. Methods: The expression level of ALYREF in pan-cancer and their normal tissues was compared through the data acquired from The Cancer Genome Atlas (TCGA). The University of Alabama at Birmingham Cancer data analysis Portal UALCAN was used to analyze the relationship between ALYREF and clinical pathological features. The relationship between the expression level of ALYREF and prognosis of pan-cancer, and the correlation genes of ALYREF were figured out by using Gene Expression Correlation Analysis database GEPIA. Immune related genes were obtained from TISIDB (an integrated repository portal for tumor-immune system interactions). Immune-related research was conducted by using Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) and TIMER. Results: Based on the data acquired from TCGA, ALYREF has an obviously higher-level expression in various types of cancers compared with relevant normal tissues excluding thyroid carcinoma and kidney chromophobe. The immunohistochemical images on The Human Protein Atlas showed that ALYREF can be detected in cytoplasm, membrane, but mainly located in nuclear. In addition, a higher expression level of ALYREF in tumor tissue generates a poor prognosis in majority of cancers. According to the above results, cancers with a higher expression level of ALYREF compared with normal tissues and a significant correlation between ALYREF and prognosis were selected for further analysis. By using TISIDB, we found that portion of ALYREF co-expression genes (such as BIRC5, H2AFZ, CCDC137, TK1, and PPM1G) with high Pearson correlation coefficient (PCC) were involved in anti-tumor immunity or affect resistance or sensitivity to T cell-mediated killing. Furthermore, based on the results acquired from GEPIA, there was significant correlation between ALYREF and PD-L1. It was exposed that there is a negative correlation between the expression level of ALYREF and ESTIMATE score. Conclusion: The present study indicated that ALYREF plays a vital and universal role in cancer initiation and progression of pan-cancer through regulating mitotic progression, DNA synthesis and metabolic process, and RNA processing. The correlation between ALYREF and PD-L1 implied ALYREF may affect the therapeutic effect of immunotherapy of tumor. More evidence revealed that ALYREF may play an important role in tumor immunomodulation. The correlation between ALYREF and immune cell infiltration level indicated that ALYREF can be a potential therapeutic target. Exploring the regulatory mechanism of ALYREF in tumor tissues may expose the reason for poor efficacy of immunotherapy and offer more directions of tumor treatment.

Keywords: ALYREF, pan-cancer, immunotherapy, PD-L1

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1493 Deposition of Size Segregated Particulate Matter in Human Respiratory Tract and Their Health Effects in Glass City Residents

Authors: Kalpana Rajouriya, Ajay Taneja

Abstract:

Particulates are ubiquitous in the air environment and cause serious threats to human beings, such as lung cancer, COPD, and Asthma. Particulates mainly arise from industrial effluent, vehicular emission, and other anthropogenic activities. In the glass industrial city Firozabad, real-time monitoring of size segregated Particulate Matter (PM) and black carbon was done by Aerosol Black Carbon Detector (ABCD) and GRIMM portable aerosol Spectrometer at two different sites in which one site is urban and another is rural. The average mass concentration of size segregated PM during the study period (March & April 2022) was recorded as PM10 (223.73 g/m⁻³), PM5.0 (44.955 g/m⁻³), PM2.5 (59.275 g/m⁻³), PM1.0 (33.02 g/m⁻³), PM0.5 (2.05 g/m⁻³), and PM0.25 (2.99 g/m⁻³). The highest concentration of BC was found in Urban due to the emissions from diesel engines and wood burning, while NO2 was highest at the rural sites. The average concentrations of PM10 (6.08 and 2.73 times) PM2.5 exceeded the NAAQS and WHO guidelines. Particulate Matter deposition and health risk assessment was done by MPPD and USEPA model to know about the particulate matter toxicity in industrial residents. Health risk assessment results showed that Children are most likely to be affected by exposure of PM10 and PM2.5 and may have various non-carcinogenic and carcinogenic diseases. Deposition results inferred that the sensitive exposed population, especially 9 years old children, have high PM deposition as well as visualization and may be at risk of developing health-related problems from exposure to size-segregated PM. They will be discussed during presentation.

Keywords: particulate matter, black carbon, NO2, deposition of PM, health risk

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1492 Designed Purine Molecules and in-silico Evaluation of Aurora Kinase Inhibition in Breast Cancer

Authors: Pooja Kumari, Anandkumar Tengli

Abstract:

Aurora kinase enzyme, a protein on overexpression, leads to metastasis and is extremely important for women’s health in terms of prevention or treatment. While creating a targeted technique, the aim of the work is to design purine molecules that inhibit in aurora kinase enzyme and helps to suppress breast cancer. Purine molecules attached to an amino acid in DNA block protein synthesis or halt the replication and metastasis caused by the aurora kinase enzyme. Various protein related to the overexpression of aurora protein was docked with purine molecule using Biovia Drug Discovery, the perpetual software. Various parameters like X-ray crystallographic structure, presence of ligand, Ramachandran plot, resolution, etc., were taken into consideration for selecting the target protein. A higher negative binding scored molecule has been taken for simulation studies. According to the available research and computational analyses, purine compounds may be powerful enough to demonstrate a greater affinity for the aurora target. Despite being clinically effective now, purines were originally meant to fight breast cancer by inhibiting the aurora kinase enzyme. In in-silico studies, it is observed that purine compounds have a moderate to high potency compared to other molecules, and our research into the literature revealed that purine molecules have a lower risk of side effects. The research involves the design, synthesis, and identification of active purine molecules against breast cancer. Purines are structurally similar to the normal metabolites of adenine and guanine; hence interfere/compete with protein synthesis and suppress the abnormal proliferation of cells/tissues. As a result, purine target metastasis cells and stop the growth of kinase; purine derivatives bind with DNA and aurora protein which may stop the growth of protein or inhibits replication and stop metastasis of overexpressed aurora kinase enzyme.

Keywords: aurora kinases, in silico studies, medicinal chemistry, combination therapies, chronic cancer, clinical translation

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1491 A Novel Bio-ceramic Using Hyperthermia for Bone Cancer Therapy, Ferro-substituted Silicate Calcium Materials

Authors: hassan gheisari

Abstract:

Ferro silicate calcium nano particles are prepared through the sol-gel method using polyvinyl alcohol (PVA) as a chelating agent. The powder, as prepared, is annealed at three different temperatures (900 ºC, 1000 ºC, and 1100 ºC) for 3 h. The XRD patterns of the samples indicate broad peaks, and the full width at half maximum decreased with increasing annealing temperature. FTIR spectra of the samples confirm the presence of metal - oxygen complexes within the structure. The average particle size obtained from PSA curve demonstrates ultrafine particles. SEM micrographs indicate the particles synthesized have spherical morphology. The saturation magnetization (Ms) and remnant magnetization (Mr) of the samples show dependence on particle size and crystallinity of the samples. The highest saturation magnetization is achieved for the sample annealed at 1100 ºC having maximum average particle size. The high saturation magnetization of the samples suggests the present method is suitable for obtaining nano particles magnetic ferro bioceramic, which is desirable for practical applications such as hyperthermia bone cancer therapy.

Keywords: hyperthermia, bone cancer, bio ceramic; magnetic materials; sol– gel, silicate calcium

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1490 Ferro-Substituted Silicate Calcium Materials, a Novel Bio-Ceramic Using Hyperthermia for Bone Cancer Therapy

Authors: Hassan Gheisari

Abstract:

Ferro silicate calcium nano particles are prepared through the sol-gel method using polyvinyl alcohol (PVA) as a chelating agent. The powder as prepared is annealed at three different temperatures (900 ºC, 1000 ºC and 1100 ºC) for 3 h. The XRD patterns of the samples indicate broad peaks and the full width at half maximum decreased with increasing annealing temperature. FTIR spectra of the samples confirm the presence of metal - oxygen complexes within the structure. The average particle size obtained from PSA curve demonstrates ultrafine particles. SEM micrographs indicate the particles synthesized have spherical morphology. The saturation magnetization (Ms) and remnant magnetization (Mr) of the samples show dependence on particle size and crystallinity of the samples. The highest saturation magnetization is achieved for the sample annealed at 1100 ºC having maximum average particle size. The high saturation magnetization of the samples suggests the present method is suitable for obtaining nano particles magnetic ferro bioceramic which is desirable for practical applications such as hyperthermia bone cancer therapy.

Keywords: hyperthermia, bone cancer, bio ceramic, magnetic materials, sol– gel, silicate calcium

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1489 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

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1488 Breast Cancer Cellular Immunotherapies

Authors: Zahra Shokrolahi, Mohammad Reza Atashzar

Abstract:

The goals of treating patients with breast cancer are to cure the disease, prolong survival, and improve quality of life. Immune cells in the tumor microenvironment have an important role in regulating tumor progression. The term of cellular immunotherapy refers to the administration of living cells to a patient; this type of immunotherapy can be active, such as a dendritic cell (DC) vaccine, in that the cells can stimulate an anti-tumour response in the patient, or the therapy can be passive, whereby the cells have intrinsic anti-tumour activity; this is known as adoptive cell transfer (ACT) and includes the use of autologous or allogeneic lymphocytes that may, or may not, be modified. The most important breast cancer cellular immunotherapies involving the use of T cells and natural killer (NK) cells in adoptive cell transfer, as well as dendritic cells vaccines. T cell-based therapies including tumour-infiltrating lymphocytes (TILs), engineered TCR-T cells, chimeric antigen receptor (CAR T cell), Gamma-delta (γδ) T cells, natural killer T (NKT) cells. NK cell-based therapies including lymphokine-activated killers (LAK), cytokine-induced killer (CIK) cells, CAR-NK cells. Adoptive cell therapy has some advantages and disadvantages some. TILs cell strictly directed against tumor-specific antigens but are inactive against tumor changes due to immunoediting. CIK cell have MHC-independent cytotoxic effect and also need concurrent high dose IL-2 administration. CAR T cell are MHC-independent; overcome tumor MHC molecule downregulation; potent in recognizing any cell surface antigen (protein, carbohydrate or glycolipid); applicable to a broad range of patients and T cell populations; production of large numbers of tumor-specific cells in a moderately short period of time. Meanwhile CAR T cells capable of targeting only cell surface antigens; lethal toxicity due to cytokine storm reported. Here we present the most popular cancer cellular immunotherapy approaches and discuss their clinical relevance referring to data acquired from clinical trials .To date, clinical experience and efficacy suggest that combining more than one immunotherapy interventions, in conjunction with other treatment options like chemotherapy, radiotherapy and targeted or epigenetic therapy, should guide the way to cancer cure.

Keywords: breast cancer , cell therapy , CAR T cell , CIK cells

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1487 Association of Airborne Emissions with Pulmonary Dysfunction, XRCC1 Gene Polymorphism, and Some Inflammatory Markers in Aluminum Workers

Authors: Gehan Moubarz, Atef M. F. Mohammed, Inas A. Saleh, Heba Mahdy-Abdallah, Amal Saad-Hussein

Abstract:

This study estimates the association between respiratory outcomes among employees of a secondary aluminum plant and airborne pollutants. Additionally, it looks into the relationship between pulmonary dysfunction in workers and XRCC1 gene polymorphisms. 110 exposed workers and 58 non-exposed workers participated in the study. Measurements have been conducted on SO₂, NO₂, and particulate particles. Pulmonary function was tested. Eosinophil cationic protein (ECP), C-reactive protein (CRP), matrix metalloproteinase-1 (MMP-1), interleukin 6 (IL6), GM-CSF, X-Ray Repair Cross Complementing 1 (XRCC1) protein, and genotyping of XRCC1 gene polymorphisms were examined. Results: The annual average concentrations of (PM₂.₅, PM₁₀, TSP, SO₂, and NO₂) were lower than the permissible limit. The areas around ovens, evaporators, and cold rolling mills exhibited the highest amounts. The majority of employees in these departments had impaired lung function. With longer exposure times, the exposed group's FEV1% and FVC% considerably reduced. The exposed workers had considerably higher XRCC1 levels. The evaluated inflammatory biomarkers showed no statistically significant difference. Conclusion: Aluminum workers are at risk of developing respiratory disorders. The level of serum XRCC1 may act as a biomarker that might be very useful for detecting susceptible workers.

Keywords: aluminum industry, particulate matter, SO₂, NO₂, lung function, XRCC1 gene polymorphism, XRCC1 protein, inflammatory biomarkers

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1486 Reframing Physical Activity for Health

Authors: M. Roberts

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We Are Undefeatable - is a mass marketing behaviour change campaign that aims to support the least active people living with long term health conditions to be more active. This is an important issue to address because people with long term conditions are an historically underserved community for the sport and physical activity sector and the least active of those with long term conditions have the most to gain in health and wellbeing benefits. The campaign has generated a significant change in the way physical activity is communicated and people with long term conditions are represented in the media and marketing. The goal is to create a social norm around being active. The campaign is led by a unique partnership of organisations: the Richmond Group of Charities (made up of Age UK, Alzheimer’s Society, Asthma + Lung UK, Breast Cancer Now, British Heart Foundation, British Red Cross, Diabetes UK, Macmillan Cancer Support, Rethink Mental Illness, Royal Voluntary Service, Stroke Association, Versus Arthritis) along with Mind, MS Society, Parkinson’s UK and Sport England, with National Lottery Funding. It is underpinned by the COM-B model of behaviour change. It draws on the lived experience of people with multiple long term conditions to shape the look and feel of the campaign and all the resources available. People with long term conditions are the campaign messengers, central to the ethos of the campaign by telling their individual stories of overcoming barriers to be active with their health conditions. The central messaging is about finding a way to be active that works for the individual. We Are Undefeatable is evaluated through a multi-modal approach, including regular qualitative focus groups and a quantitative evaluation tracker undertaken three times a year. The campaign has highlighted the significant barriers to physical activity for people with long term conditions. This has changed the way our partnership talks about physical activity but has also had an impact on the wider sport and physical activity sector, prompting an increasing departure from traditional messaging and marketing approaches for this audience of people with long term conditions. The campaign has reached millions of people since its launch in 2019, through multiple marketing and partnership channels including primetime TV advertising and promotion through health professionals and in health settings. Its diverse storytellers make it relatable to its target audience and the achievable activities highlighted and inclusive messaging inspire our audience to take action as a result of seeing the campaign. The We Are Undefeatable campaign is a blueprint for physical activity campaigns; it not only addresses individual behaviour change but plays a role in addressing systemic barriers to physical activity by sharing the lived experience insight to shape policy and professional practice.

Keywords: behaviour change, long term conditions, partnership, relatable

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1485 The Factors That Influence the Self-Sufficiency and the Self-Efficacy Levels among Oncology Patients

Authors: Esra Danaci, Tugba Kavalali Erdogan, Sevil Masat, Selin Keskin Kiziltepe, Tugba Cinarli, Zeliha Koc

Abstract:

This study was conducted in a descriptive and cross-sectional manner to determine that factors that influence the self-efficacy and self-sufficiency levels among oncology patients. The research was conducted between January 24, 2017 and September 24, 2017 in the oncology and hematology departments of a university hospital in Turkey with 179 voluntary inpatients. The data were collected through the Self-Sufficiency/Self-Efficacy Scale and a 29-question survey, which was prepared in order to determine the sociodemographic and clinical properties of the patients. The Self-Sufficiency/Self-Efficacy Scale is a Likert-type scale with 23 articles. The scale scores range between 23 and 115. A high final score indicates a good self-sufficiency/self-efficacy perception for the individual. The data were analyzed using percentage analysis, one-way ANOVA, Mann Whitney U-test, Kruskal Wallis test and Tukey test. The demographic data of the subjects were as follows: 57.5% were male and 42.5% were female, 82.7% were married, 46.4% were primary school graduate, 36.3% were housewives, 19% were employed, 93.3% had social security, 52.5% had matching expenses and incomes, 49.2% lived in the center of the city. The mean age was 57.1±14.6. It was determined that 22.3% of the patients had lung cancer, 19.6% had leukemia, and 43.6% had a good overall condition. The mean self-sufficiency/self-efficacy score was 83,00 (41-115). It was determined that the patients' self-sufficiency/self-efficacy scores were influenced by some of their socio-demographic and clinical properties. This study has found that the patients had high self-sufficiency/self-efficacy scores. It is recommended that the nursing care plans should be developed to improve their self-sufficiency/self-efficacy levels in the light of the patients' sociodemographic and clinical properties.

Keywords: oncology, patient, self-efficacy, self-sufficiency

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1484 In silico Repopulation Model of Various Tumour Cells during Treatment Breaks in Head and Neck Cancer Radiotherapy

Authors: Loredana G. Marcu, David Marcu, Sanda M. Filip

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Advanced head and neck cancers are aggressive tumours, which require aggressive treatment. Treatment efficiency is often hindered by cancer cell repopulation during radiotherapy, which is due to various mechanisms triggered by the loss of tumour cells and involves both stem and differentiated cells. The aim of the current paper is to present in silico simulations of radiotherapy schedules on a virtual head and neck tumour grown with biologically realistic kinetic parameters. Using the linear quadratic formalism of cell survival after radiotherapy, altered fractionation schedules employing various treatment breaks for normal tissue recovery are simulated and repopulation mechanism implemented in order to evaluate the impact of various cancer cell contribution on tumour behaviour during irradiation. The model has shown that the timing of treatment breaks is an important factor influencing tumour control in rapidly proliferating tissues such as squamous cell carcinomas of the head and neck. Furthermore, not only stem cells but also differentiated cells, via the mechanism of abortive division, can contribute to malignant cell repopulation during treatment.

Keywords: radiation, tumour repopulation, squamous cell carcinoma, stem cell

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1483 Evaluation of the Cytotoxicity and Cellular Uptake of a Cyclodextrin-Based Drug Delivery System for Cancer Therapy

Authors: Caroline Mendes, Mary McNamara, Orla Howe

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Drug delivery systems are proposed for use in cancer treatment to specifically target cancer cells and deliver a therapeutic dose without affecting normal cells. For that purpose, the use of folate receptors (FR) can be considered a key strategy, since they are commonly over-expressed in cancer cells. In this study, cyclodextrins (CD) have being used as vehicles to target FR and deliver the chemotherapeutic drug, methotrexate (MTX). CDs have the ability to form inclusion complexes, in which molecules of suitable dimensions are included within their cavities. Here, β-CD has been modified using folic acid so as to specifically target the FR. Thus, this drug delivery system consists of β-CD, folic acid and MTX (CDEnFA:MTX). Cellular uptake of folic acid is mediated with high affinity by folate receptors while the cellular uptake of antifolates, such as MTX, is mediated with high affinity by the reduced folate carriers (RFCs). This study addresses the gene (mRNA) and protein expression levels of FRs and RFCs in the cancer cell lines CaCo-2, SKOV-3, HeLa, MCF-7, A549 and the normal cell line BEAS-2B, quantified by real-time polymerase chain reaction (real-time PCR) and flow cytometry, respectively. From that, four cell lines with different levels of FRs, were chosen for cytotoxicity assays of MTX and CDEnFA:MTX using the MTT assay. Real-time PCR and flow cytometry data demonstrated that all cell lines ubiquitously express moderate levels of RFC. These experiments have also shown that levels of FR protein in CaCo-2 cells are high, while levels in SKOV-3, HeLa and MCF-7 cells are moderate. A549 and BEAS-2B cells express low levels of FR protein. FRs are highly expressed in all the cancer cell lines analysed when compared to the normal cell line BEAS-2B. The cell lines CaCo-2, MCF-7, A549 and BEAS-2B were used in the cell viability assays. 48 hours treatment with the free drug and the complex resulted in IC50 values of 93.9 µM ± 15.2 and 56.0 µM ± 4.0 for CaCo-2 for free MTX and CDEnFA:MTX respectively, 118.2 µM ± 16.8 and 97.8 µM ± 12.3 for MCF-7, 36.4 µM ± 6.9 and 75.0 µM ± 10.5 for A549 and 132.6 µM ± 16.1 and 288.1 µM ± 26.3 for BEAS-2B. These results demonstrate that free MTX is more toxic towards cell lines expressing low levels of FR, such as the BEAS-2B. More importantly, these results demonstrate that the inclusion complex CDEnFA:MTX showed greater cytotoxicity than the free drug towards the high FR expressing CaCo-2 cells, indicating that it has potential to target this receptor, enhancing the specificity and the efficiency of the drug. The use of cell imaging by confocal microscopy has allowed visualisation of FR targeting in cancer cells, as well as the identification of the interlisation pathway of the drug. Hence, the cellular uptake and internalisation process of this drug delivery system is being addressed.

Keywords: cancer treatment, cyclodextrins, drug delivery, folate receptors, reduced folate carriers

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1482 Pegylated Liposomes of Trans Resveratrol, an Anticancer Agent, for Enhancing Therapeutic Efficacy and Long Circulation

Authors: M. R. Vijayakumar, Sanjay Kumar Singh, Lakshmi, Hithesh Dewangan, Sanjay Singh

Abstract:

Trans resveratrol (RES) is a natural molecule proved for cancer preventive and therapeutic activities devoid of any potential side effects. However, the therapeutic application of RES in disease management is limited because of its rapid elimination from blood circulation thereby low biological half life in mammals. Therefore, the main objective of this study is to enhance the circulation as well as therapeutic efficacy using PEGylated liposomes. D-α-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS) is applied as steric surface decorating agent to prepare RES liposomes by thin film hydration method. The prepared nanoparticles were evaluated by various state of the art techniques such as dynamic light scattering (DLS) technique for particle size and zeta potential, TEM for shape, differential scanning calorimetry (DSC) for interaction analysis and XRD for crystalline changes of drug. Encapsulation efficiency and invitro drug release were determined by dialysis bag method. Cancer cell viability studies were performed by MTT assay, respectively. Pharmacokinetic studies were performed in sprague dawley rats. The prepared liposomes were found to be spherical in shape. Particle size and zeta potential of prepared formulations varied from 64.5±3.16 to 262.3±7.45 nm and -2.1 to 1.76 mV, respectively. DSC study revealed absence of potential interaction. XRD study revealed presence of amorphous form in liposomes. Entrapment efficiency was found to be 87.45±2.14 % and the drug release was found to be controlled up to 24 hours. Minimized MEC in MTT assay and tremendous enhancement in circulation time of RES PEGylated liposomes than its pristine form revealed that the stearic stabilized PEGylated liposomes can be an alternative tool to commercialize this molecule for chemopreventive and therapeutic applications in cancer.

Keywords: trans resveratrol, cancer nanotechnology, long circulating liposomes, bioavailability enhancement, liposomes for cancer therapy, PEGylated liposomes

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1481 A Study on the Application of Machine Learning and Deep Learning Techniques for Skin Cancer Detection

Authors: Hritwik Ghosh, Irfan Sadiq Rahat, Sachi Nandan Mohanty, J. V. R. Ravindra

Abstract:

In the rapidly evolving landscape of medical diagnostics, the early detection and accurate classification of skin cancer remain paramount for effective treatment outcomes. This research delves into the transformative potential of Artificial Intelligence (AI), specifically Deep Learning (DL), as a tool for discerning and categorizing various skin conditions. Utilizing a diverse dataset of 3,000 images representing nine distinct skin conditions, we confront the inherent challenge of class imbalance. This imbalance, where conditions like melanomas are over-represented, is addressed by incorporating class weights during the model training phase, ensuring an equitable representation of all conditions in the learning process. Our pioneering approach introduces a hybrid model, amalgamating the strengths of two renowned Convolutional Neural Networks (CNNs), VGG16 and ResNet50. These networks, pre-trained on the ImageNet dataset, are adept at extracting intricate features from images. By synergizing these models, our research aims to capture a holistic set of features, thereby bolstering classification performance. Preliminary findings underscore the hybrid model's superiority over individual models, showcasing its prowess in feature extraction and classification. Moreover, the research emphasizes the significance of rigorous data pre-processing, including image resizing, color normalization, and segmentation, in ensuring data quality and model reliability. In essence, this study illuminates the promising role of AI and DL in revolutionizing skin cancer diagnostics, offering insights into its potential applications in broader medical domains.

Keywords: artificial intelligence, machine learning, deep learning, skin cancer, dermatology, convolutional neural networks, image classification, computer vision, healthcare technology, cancer detection, medical imaging

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1480 Association of miRNA146a rs2910164 Polymorphism and Helicobacter pylori Infection in Colorectal Cancer

Authors: Zahra Solgi, Hossein Rassi

Abstract:

Colorectal cancer (CRC) is a multi-step disease, and chronic gastric infection with H. pylori could play a role in one or more of the steps in this pathogenic process. Polymorphisms in several miRNAs are considered to increase the risk for the development of CRC by controlling proliferation, apoptosis and H. pylori pathogenesis. Therefore, the aim of this study was to investigate miRNA146a rs2910164 polymorphism and Helicobacter pylori infection in CRC. A total of 65 patients with CRC were divided into 2 groups: 28 patients < 50 years of age and 37 patients ≥ 50 years of age. DNA was extracted from all samples by a standard method and H. pylori cagA and miRNA146a rs2910164 genotypes were determined by PCR method. The results show that there was no significant difference in the frequency of H. pylori cagA gene between the two groups but there was a significant difference in the distribution of rs2910164 genotypes in patients < 50 years of age with the p-value of 0.05 and odds ratio equal to 2.69. On other hand, patients < 50 years of age with genotype CC of miRNA146a showed a significant difference in CRC risk. Furthermore, there was a significant correlation between rs2910164 CC genotype with Helicobacter pylori infection in patients < 50 years of age. The present study suggests that the CC genotype of miRNA146a in combination with H. pylori infection can be effective as risk factors and molecular markers for early diagnosis and treatment of CRC.

Keywords: colorectal cancer, Helicobacter pylori, miRNA146a, rs2910164 polymorphism

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1479 Evaluating the Effectiveness of Combined Psychiatric and Psychotherapeutic Care versus Psychotherapy Alone in the Treatment of Depression and Anxiety in Cancer Patients

Authors: Nathen A. Spitz, Dennis Martin Kivlighan III, Arwa Aburizik

Abstract:

Background and Purpose: Presently, there is a paucity of naturalistic studies that directly compare the effectiveness of psychotherapy versus concurrent psychotherapy and psychiatric care for the treatment of depression and anxiety in cancer patients. Informed by previous clinical trials examining the efficacy of concurrent approaches, this study sought to test the hypothesis that a combined approach would result in the greatest reduction of depression and anxiety symptoms. Methods: Data for this study consisted of 433 adult cancer patients, with 252 receiving only psychotherapy and 181 receiving concurrent psychotherapy and psychiatric care at the University of Iowa Hospitals and Clinics. Longitudinal PHQ9 and GAD7 data were analyzed between both groups using latent growth curve analyses. Results: After controlling for treatment length and provider effects, results indicated that concurrent care was more effective than psychotherapy alone for depressive symptoms (γ₁₂ = -0.12, p = .037). Specifically, the simple slope for concurrent care was -0.25 (p = .022), and the simple slope for psychotherapy alone was -0.13 (p = .006), suggesting that patients receiving concurrent care experienced a greater reduction in depressive symptoms compared to patients receiving psychotherapy alone. In contrast, there were no significant differences between psychotherapy alone and concurrent psychotherapy and psychiatric care in the reduction of anxious symptoms. Conclusions: Overall, as both psychotherapy and psychiatric care may address unique aspects of mental health conditions, in addition to potentially providing synergetic support to each other, a combinatorial approach to mental healthcare for cancer patients may improve outcomes.

Keywords: psychiatry, psychology, psycho-oncology, combined care, psychotherapy, behavioral psychology

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1478 Fuzzy Optimization for Identifying Anticancer Targets in Genome-Scale Metabolic Models of Colon Cancer

Authors: Feng-Sheng Wang, Chao-Ting Cheng

Abstract:

Developing a drug from conception to launch is costly and time-consuming. Computer-aided methods can reduce research costs and accelerate the development process during the early drug discovery and development stages. This study developed a fuzzy multi-objective hierarchical optimization framework for identifying potential anticancer targets in a metabolic model. First, RNA-seq expression data of colorectal cancer samples and their healthy counterparts were used to reconstruct tissue-specific genome-scale metabolic models. The aim of the optimization framework was to identify anticancer targets that lead to cancer cell death and evaluate metabolic flux perturbations in normal cells that have been caused by cancer treatment. Four objectives were established in the optimization framework to evaluate the mortality of cancer cells for treatment and to minimize side effects causing toxicity-induced tumorigenesis on normal cells and smaller metabolic perturbations. Through fuzzy set theory, a multiobjective optimization problem was converted into a trilevel maximizing decision-making (MDM) problem. The applied nested hybrid differential evolution was applied to solve the trilevel MDM problem using two nutrient media to identify anticancer targets in the genome-scale metabolic model of colorectal cancer, respectively. Using Dulbecco’s Modified Eagle Medium (DMEM), the computational results reveal that the identified anticancer targets were mostly involved in cholesterol biosynthesis, pyrimidine and purine metabolisms, glycerophospholipid biosynthetic pathway and sphingolipid pathway. However, using Ham’s medium, the genes involved in cholesterol biosynthesis were unidentifiable. A comparison of the uptake reactions for the DMEM and Ham’s medium revealed that no cholesterol uptake reaction was included in DMEM. Two additional media, i.e., a cholesterol uptake reaction was included in DMEM and excluded in HAM, were respectively used to investigate the relationship of tumor cell growth with nutrient components and anticancer target genes. The genes involved in the cholesterol biosynthesis were also revealed to be determinable if a cholesterol uptake reaction was not induced when the cells were in the culture medium. However, the genes involved in cholesterol biosynthesis became unidentifiable if such a reaction was induced.

Keywords: Cancer metabolism, genome-scale metabolic model, constraint-based model, multilevel optimization, fuzzy optimization, hybrid differential evolution

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1477 Methodology for Diagnosing Architecture Improvements in a Cancer Hospital in Brasilia

Authors: Mariana Sabino, Janes Cleiton de Oliveira, Carlos Luna de Melo

Abstract:

This paper presents a discussion about the importance and influence of the environment in the patient’s recovery process. Some users (employees and patients) were submitted to a questionnaire that helps to diagnoses the major problems of the hospital, specially related to comfort (aesthetic, thermal, acoustic, light, ergonomic), well-being, how does the flow of patients and employees works in the hospital and wayfinding as well. After a short literature review presenting the topic, the hospital will be characterized, showing photos, the projects available and describing the hospital as well (how many rooms, functions of each one, receptions, waiting rooms, between other things.), than the questionnaire will be applied to patients and to the employees. Lastly the results of the answers given will be analyzed in graphics, and it will help to identify which are the major improvements needed immediately. This paper has the intention to propose a methodology to diagnose architecture problems in a cancer hospital in Brasilia, Brazil, besides to open a space to hear the people that use the building to tell about their discomforts and perceptions of the environment, it also will give an opportunity to apply the possible improvements. It is important to tell that it will be considered if the hospital has a healing environment, and it will also be considered the ergonomic issues about comfort and the way the system of this particular hospital works in general.

Keywords: cancer hospital, comfort, diagnose, healing environment

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1476 Analysis of Relative Gene Expression Data of GATA3-AS1 Associated with Resistance to Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer Patients of Luminal B Subtype

Authors: X. Cervantes-López, C. Arriaga-Canon, L. Contreras Espinosa

Abstract:

The goal of this study is to validate the overexpression of the lncRNA GATA3-AS1 associated with resistance to neoadjuvant chemotherapy of female patients with locally advanced mammary adenocarcinoma of luminal B subtype This study involved a cohort of one hundred thirty-seven samples for which total RNA was isolated from formalin fixed paraffin embedded (FFPE) tissue. Samples were cut using a Microtome Hyrax M25 Zeiss and RNA was isolated using the RNeasy FFPE kit and a deparaffinization solution, the next step consisted in the analysis of RNA concentration and quality, then 18 µg of RNA was treated with DNase I, and cDNA was synthesized from 50 ng total RNA, finally real-time PCR was performed with SYBR Green/ROX qPCR Master Mix in order to determined relative gene expression using RPS28 as a housekeeping gene to normalize in a fold calculation ΔCt. As a result, we validated by real-time PCR that the overexpression of the lncRNA GATA3-AS1 is associated with resistance to neoadjuvant chemotherapy in locally advanced breast cancer patients of luminal B subtype.

Keywords: breast cancer, biomarkers, genomics, neoadjuvant chemotherapy, lncRNAS

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1475 Literature Review of Empirical Studies on the Psychological Processes of End-of-Life Cancer Patients

Authors: Kimiyo Shimomai, Mihoko Harada

Abstract:

This study is a literature review of the psychological reactions that occur in end-of-life cancer patients who are nearing death. It searched electronic databases and selected literature related to psychological studies of end-of-life patients. There was no limit on the search period, and the search was conducted until the second week of December 2021. The keywords were specified as “death and dying”, “terminal illness”, “end-of-life”, “palliative care”, “psycho-oncology” and “research”. These literatures referred to Holly (2017): Comprehensive Systematic Review for Advanced Practice Nursing, P268 Figure 10.3 to ensure quality. These literatures were selected with a dissertation score of 4 or 5. The review was conducted in two stages with reference to the procedure of George (2002). First, these references were searched for keywords in the database, and then relevant references were selected from the psychology and nursing studies of end-of-life patients. The number of literatures analyzed was 76 for overseas and 17 for domestic. As for the independent variables, "physical variable" was the most common in 36 literatures (66.7%), followed by "psychological variable" in 35 literatures (64.8%), "spiritual variable" in 21 literatures (38%), and "social variable" in 17 literatures. (31.5%), "Variables related to medical care / treatment" were 16 literatures (29.6%). To summarize the relationship between these independent variables and the dependent variable, when the dependent variable is "psychological variable", the independent variables are "psychological variable", "social variable", and "physical variable". Among the independent variables, the physical variables were the most common. The psychological responses that occur in end-stage cancer patients who are nearing death are mutually influenced by psychological, social, and physical variables. Therefore, it supported the "total pain" advocated by Cicely Saunders.

Keywords: cancer patient, end-of-life, literature review, psychological process

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1474 Mammographic Multi-View Cancer Identification Using Siamese Neural Networks

Authors: Alisher Ibragimov, Sofya Senotrusova, Aleksandra Beliaeva, Egor Ushakov, Yuri Markin

Abstract:

Mammography plays a critical role in screening for breast cancer in women, and artificial intelligence has enabled the automatic detection of diseases in medical images. Many of the current techniques used for mammogram analysis focus on a single view (mediolateral or craniocaudal view), while in clinical practice, radiologists consider multiple views of mammograms from both breasts to make a correct decision. Consequently, computer-aided diagnosis (CAD) systems could benefit from incorporating information gathered from multiple views. In this study, the introduce a method based on a Siamese neural network (SNN) model that simultaneously analyzes mammographic images from tri-view: bilateral and ipsilateral. In this way, when a decision is made on a single image of one breast, attention is also paid to two other images – a view of the same breast in a different projection and an image of the other breast as well. Consequently, the algorithm closely mimics the radiologist's practice of paying attention to the entire examination of a patient rather than to a single image. Additionally, to the best of our knowledge, this research represents the first experiments conducted using the recently released Vietnamese dataset of digital mammography (VinDr-Mammo). On an independent test set of images from this dataset, the best model achieved an AUC of 0.87 per image. Therefore, this suggests that there is a valuable automated second opinion in the interpretation of mammograms and breast cancer diagnosis, which in the future may help to alleviate the burden on radiologists and serve as an additional layer of verification.

Keywords: breast cancer, computer-aided diagnosis, deep learning, multi-view mammogram, siamese neural network

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1473 An Audit of Restaging Transurethral Resection of Bladder Tumor (Re-TURBT) Quality in a District General Hospital

Authors: Rizwan Iqbal

Abstract:

Introduction: Re-TURBT has been recommended by international guidelines for patients with non-muscle invasive bladder cancer (NMIBC) who are deemed high-risk. Indications for re-TURBTs remain controversial and studies show mixed outcomes. It should be performed when the initial TURBT specimen lacks detrusor muscle, has tumor stage pT1 or G3/high-grade, or where resection is deemed incomplete. This ensures complete resection of tumors that have a high risk of recurrence as well as accurately identifying any tumors which have been upstaged. The aim of this audit was to evaluate the quality of re-TURBTs in a district general hospital. Method: Data were retrospectively collected from 31 patients who had re-TURBTs between April 2021 and September 2022. Data included baseline demographics, time from initial to re-TURBT, quality of operation note, presence of residual tumor, complications, and administration of chemotherapy within 24 hours of the initial TURBT. Data collection remains ongoing at the time of writing. Results: The mean age was 76 years old and 71.0% of patients were male. 32.3% of patients had their re-TURBT within six weeks and 32.3% had intravesical chemotherapy administered within 24 hours of the initial TURBT. 74.2% of initial TURBTs had detrusor muscle present in the specimen. 48.4% of patients had residual disease following re-TURBT. Just one patient had their pathology upstaged at re-TURBT. The use of the TURBT proforma on the operation note was variable, with 51.6% and 38.7% of surgeons using the proforma after the initial and re-TURBT. Conclusion: Re-TURBT improves bladder cancer staging and is necessary in patients who are deemed high-risk in order to identify any upstaging or recurrence of the disease.

Keywords: urology, bladder cancer, turbt, cancer

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1472 18 F-FDG PET/CT: Utility in Breast Cancer Surgery

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

Abstract:

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

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

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1471 Modulation of Tamoxifen-Induced Cytotoxicity in Breast Cancer Cell Lines by 3-Bromopyruvate

Authors: Yasmin M. Attia, Hanan S. El-Abhar, Mahmoud M. Al Marzabani, Samia A. Shouman

Abstract:

Background: Tamoxifen (TAM) is the most commonly used hormone therapy for the treatment of early and metastatic breast cancer. Although it significantly decreases the tumor recurrence rate and provides an overall benefit, as much as 20–30% of women still relapse during or after long-term therapy. 3-Bromopyruvate (3-BP) is a promising agent with impressive antitumor effects in several models of animal tumors and cell lines. Aim: This study was designed to investigate the combined effect of (TAM) and (3-BP) in breast cancer cells and to explore their molecular interaction via assessment of apoptotic, angiogenic, and metastatic markers. Methods: In vitro cytotoxicity study was carried out for both compounds to determine the combination regimen producing a synergistic effect and mechanistic pathways were studied using RT-PCR and western techniques. Moreover, the anti-oncolytic and anti-angiogenic potentials were assessed in mice bearing solid Ehrlich carcinoma (SEC). Results: The combined treatment significantly increased the expressions and protein levels of caspase 7, 9, and 3 and decreased of angiogenic markers VEGF, HIF-1α, and HK2 compared to cells treated with either drug individually. However, there were no significant changes in MMP-2 and MMP-9 protein levels. Interestingly, the in vivo results supported the in vitro findings; there was a decrease in the tumor volume and VEFG using immunohistochemistry in the combination-treated groups compared to either TAM or 3-BP treated one. Conclusion: 3-BP synergizes the cytotoxic effect of TAM by increasing apoptosis and decreasing angiogenesis which makes this combination a promising regimen to be applied clinically.

Keywords: tamoxifen, 3-bromopyruvate, breast cancer, cytotoxicity, angiogenesis

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1470 Autophagy Suppresses Tumorigenesis through Upregulation of MiR-449a in Colorectal Cancer

Authors: Sheng-Hui Lan, Shan-Ying Wu, Shu-Ching Lin, Wei-Chen Wang, Hsiao-Sheng Liu

Abstract:

Autophagy is an essential mechanism to maintain cellular homeostasis through its degradation function, and the autophagy deficiency is related various diseases including tumorigenesis in several cancers. MicroRNAs (miRNAs) are small none coding RNAs, which regulate gene expression through degradation of mRNA or inhibition of translation. However, the relationship between autophagy deficiency and dysregulated miRNAs is still unclear. We revealed a mechanism that autophagy up-regulates miR-449a expression at the transcriptional level through activation of forkhead transcription factor family member FoxO1 and then suppresses tumorigenesis in CRC. Our data showed that the autophagic activity and miR-449a expression were lower in colorectal cancer (CRC) and has a positive correlation. We further reveal that autophagy degrades p300 expression and then suppresses acetylation of FoxO1. Under autophagic induction conditions, FoxO1 is transported from the cytoplasm to the nucleus and binds to the miR-449a promoter and then promotes miR-449a expression. In addition, either miR-449a overexpression or amiodarone-induced autophagy inhibits cell cycle progression, proliferation, colony formation migration, invasion, and tumor formation of SW480 cells. Our findings indicate that autophagy inducers may have the potential to be used for prevention and treatment of CRC through upregulation of miR-449a expression.

Keywords: autophagy, MiR-449a, FoxO1, colorectal cancer

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1469 Anti-proliferative Activity and HER2 Receptor Expression Analysis of MCF-7 (Breast Cancer Cell) Cells by Plant Extract Coleus Barbatus (Andrew)

Authors: Anupalli Roja Rani, Pavithra Dasari

Abstract:

Background: Among several, breast cancer has emerged as the most common female cancer in developing countries. It is the most common cause of cancer-related deaths worldwide among women. It is a molecularly and clinically heterogeneous disease. Moreover, it is a hormone–dependent tumor in which estrogens can regulate the growth of breast cells by binding with estrogen receptors (ERs). Moreover, the use of natural products in cancer therapeutics is due to their properties of biocompatibility and less toxicity. Plants are the vast reservoirs for various bioactive compounds. Coleus barbatus (Lamiaceae) contains anticancer properties against several cancer cell lines. Method: In the present study, an attempt is being made to enrich the knowledge of the anticancer activity of pure compounds extracted from Coleus barbatus (Andrew). On human breast cancer cell lines MCF-7. Here in, we are assessing the antiproliferative activity of Coleus barbatus (Andrew) plant extracts against MCF 7 and also evaluating their toxicity in normal human mammary cell lines such as Human Mammary Epithelial Cells (HMEC). The active fraction of plant extract was further purified with the help of Flash chromatography, Medium Pressure Liquid Chromatography (MPLC) and preparative High-Performance Liquid Chromatography (HPLC). The structure of pure compounds will be elucidated by using modern spectroscopic methods like Nuclear magnetic resonance (NMR), Electrospray Ionisation Mass Spectrometry (ESI-MS) methods. Later, the growth inhibition morphological assessment of cancer cells and cell cycle analysis of purified compounds were assessed using FACS. The growth and progression of signaling molecules HER2, GRP78 was studied by secretion assay using ELISA and expression analysis by flow cytometry. Result: Cytotoxic effect against MCF-7 with IC50 values were derived from dose response curves, using six concentrations of twofold serially diluted samples, by SOFTMax Pro software (Molecular device) and respectively Ellipticine and 0.5% DMSO were used as a positive and negative control. Conclusion: The present study shows the significance of various bioactive compounds extracted from Coleus barbatus (Andrew) root material. It acts as an anti-proliferative and shows cytotoxic effects on human breast cancer cell lines MCF7. The plant extracts play an important role pharmacologically. The whole plant has been used in traditional medicine for decades and the studies done have authenticated the practice. Earlier, as described, the plant has been used in the ayurveda and homeopathy medicine. However, more clinical and pathological studies must be conducted to investigate the unexploited potential of the plant. These studies will be very useful for drug designing in the future.

Keywords: coleus barbatus, HPLC, MPLC, NMR, MCF7, flash chromatograph, ESI-MS, FACS, ELISA.

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1468 Predictive Value of ¹⁸F-Fdg Accumulation in Visceral Fat Activity to Detect Colorectal Cancer Metastases

Authors: Amil Suleimanov, Aigul Saduakassova, Denis Vinnikov

Abstract:

Objective: To assess functional visceral fat (VAT) activity evaluated by ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography/computed tomography (PET/CT) as a predictor of metastases in colorectal cancer (CRC). Materials and methods: We assessed 60 patients with histologically confirmed CRC who underwent 18F-FDG PET/CT after a surgical treatment and courses of chemotherapy. Age, histology, stage, and tumor grade were recorded. Functional VAT activity was measured by maximum standardized uptake value (SUVmax) using ¹⁸F-FDG PET/CT and tested as a predictor of later metastases in eight abdominal locations (RE – Epigastric Region, RLH – Left Hypochondriac Region, RRL – Right Lumbar Region, RU – Umbilical Region, RLL – Left Lumbar Region, RRI – Right Inguinal Region, RP – Hypogastric (Pubic) Region, RLI – Left Inguinal Region) and pelvic cavity (P) in the adjusted regression models. We also report the best areas under the curve (AUC) for SUVmax with the corresponding sensitivity (Se) and specificity (Sp). Results: In both adjusted for age regression models and ROC analysis, 18F-FDG accumulation in RLH (cutoff SUVmax 0.74; Se 75%; Sp 61%; AUC 0.668; p = 0.049), RU (cutoff SUVmax 0.78; Se 69%; Sp 61%; AUC 0.679; p = 0.035), RRL (cutoff SUVmax 1.05; Se 69%; Sp 77%; AUC 0.682; p = 0.032) and RRI (cutoff SUVmax 0.85; Se 63%; Sp 61%; AUC 0.672; p = 0.043) could predict later metastases in CRC patients, as opposed to age, sex, primary tumor location, tumor grade and histology. Conclusions: VAT SUVmax is significantly associated with later metastases in CRC patients and can be used as their predictor.

Keywords: ¹⁸F-FDG, PET/CT, colorectal cancer, predictive value

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