Search results for: lung cancer detection
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 5401

Search results for: lung cancer detection

5161 Copper Chelation by 3-(Bromoacetyl) Coumarin Derivative Induced Apoptosis in Cancer Cells: Influence of Copper Chelation Strategy in Cancer Treatment

Authors: Saman Khan, Imrana Naseem

Abstract:

Copper is an essential trace element required for pro-angiogenic co-factors including vascular endothelial growth factor (VEGF). Elevated levels of copper are found in various types of cancer including prostrate, colon, breast, lung and liver for angiogensis and metastasis. Therefore, targeting copper via copper-specific chelators in cancer cells can be developed as effective anticancer treatment strategy. In continuation of our pursuit to design and synthesize copper chelators, herein we opted for a reaction to incorporate di-(2-picolyl) amine in 3-(bromoacetyl) coumarin (parent backbone) for the synthesis of complex 1. We evaluated lipid peroxidation, protein carbonylation, ROS generation, DNA damage and consequent apoptosis by complex 1 in exogenously added Cu(II) in human peripheral lymphocytes (simulate malignancy condition). Results showed that Cu(II)-complex 1 interaction leads to cell proliferation inhibition, apoptosis, ROS generation and DNA damage in human lymphocytes, and these effects were abrogated by cuprous chelator neocuproine and ROS scavengers (thiourea, catalase, SOD). This indicates that complex 1 cytotoxicity is due to redox cycling of copper to generate ROS which leads to pro-oxidant cell death in cancer cells. To further confirm our hypothesis, using the rat model of diethylnitrosamine (DEN) induced hepatocellular carcinoma; we showed that complex 1 mediates DNA breakage and cell death in isolated carcinoma cells. Membrane permeant copper chelator, neocuproine, and ROS scavengers inhibited the complex 1-mediated cellular DNA degradation and apoptosis. In summary, complex 1 anticancer activity is due to its copper chelation capability. These results will provide copper chelation as an effective targeted cancer treatment strategy for selective cytotoxic action against malignant cells without affecting normal cells.

Keywords: cancer treatment, copper chelation, ROS generation, DNA damage, redox cycling, apoptosis

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5160 Current Applications of Artificial Intelligence (AI) in Chest Radiology

Authors: Angelis P. Barlampas

Abstract:

Learning Objectives: The purpose of this study is to inform briefly the reader about the applications of AI in chest radiology. Background: Currently, there are 190 FDA-approved radiology AI applications, with 42 (22%) pertaining specifically to thoracic radiology. Imaging findings OR Procedure details Aids of AI in chest radiology1: Detects and segments pulmonary nodules. Subtracts bone to provide an unobstructed view of the underlying lung parenchyma and provides further information on nodule characteristics, such as nodule location, nodule two-dimensional size or three dimensional (3D) volume, change in nodule size over time, attenuation data (i.e., mean, minimum, and/or maximum Hounsfield units [HU]), morphological assessments, or combinations of the above. Reclassifies indeterminate pulmonary nodules into low or high risk with higher accuracy than conventional risk models. Detects pleural effusion . Differentiates tension pneumothorax from nontension pneumothorax. Detects cardiomegaly, calcification, consolidation, mediastinal widening, atelectasis, fibrosis and pneumoperitoneum. Localises automatically vertebrae segments, labels ribs and detects rib fractures. Measures the distance from the tube tip to the carina and localizes both endotracheal tubes and central vascular lines. Detects consolidation and progression of parenchymal diseases such as pulmonary fibrosis or chronic obstructive pulmonary disease (COPD).Can evaluate lobar volumes. Identifies and labels pulmonary bronchi and vasculature and quantifies air-trapping. Offers emphysema evaluation. Provides functional respiratory imaging, whereby high-resolution CT images are post-processed to quantify airflow by lung region and may be used to quantify key biomarkers such as airway resistance, air-trapping, ventilation mapping, lung and lobar volume, and blood vessel and airway volume. Assesses the lung parenchyma by way of density evaluation. Provides percentages of tissues within defined attenuation (HU) ranges besides furnishing automated lung segmentation and lung volume information. Improves image quality for noisy images with built-in denoising function. Detects emphysema, a common condition seen in patients with history of smoking and hyperdense or opacified regions, thereby aiding in the diagnosis of certain pathologies, such as COVID-19 pneumonia. It aids in cardiac segmentation and calcium detection, aorta segmentation and diameter measurements, and vertebral body segmentation and density measurements. Conclusion: The future is yet to come, but AI already is a helpful tool for the daily practice in radiology. It is assumed, that the continuing progression of the computerized systems and the improvements in software algorithms , will redder AI into the second hand of the radiologist.

Keywords: artificial intelligence, chest imaging, nodule detection, automated diagnoses

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5159 A Comparative Time-Series Analysis and Deep Learning Projection of Innate Radon Gas Risk in Canadian and Swedish Residential Buildings

Authors: Selim M. Khan, Dustin D. Pearson, Tryggve Rönnqvist, Markus E. Nielsen, Joshua M. Taron, Aaron A. Goodarzi

Abstract:

Accumulation of radioactive radon gas in indoor air poses a serious risk to human health by increasing the lifetime risk of lung cancer and is classified by IARC as a category one carcinogen. Radon exposure risks are a function of geologic, geographic, design, and human behavioural variables and can change over time. Using time series and deep machine learning modelling, we analyzed long-term radon test outcomes as a function of building metrics from 25,489 Canadian and 38,596 Swedish residential properties constructed between 1945 to 2020. While Canadian and Swedish properties built between 1970 and 1980 are comparable (96–103 Bq/m³), innate radon risks subsequently diverge, rising in Canada and falling in Sweden such that 21st Century Canadian houses show 467% greater average radon (131 Bq/m³) relative to Swedish equivalents (28 Bq/m³). These trends are consistent across housing types and regions within each country. The introduction of energy efficiency measures within Canadian and Swedish building codes coincided with opposing radon level trajectories in each nation. Deep machine learning modelling predicts that, without intervention, average Canadian residential radon levels will increase to 176 Bq/m³ by 2050, emphasizing the importance and urgency of future building code intervention to achieve systemic radon reduction in Canada.

Keywords: radon health risk, time-series, deep machine learning, lung cancer, Canada, Sweden

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5158 Phylogenetic Study of L1 Protein Human Papillomavirus Type 16 From Cervical Cancer Patients in Bandung

Authors: Fitri Rahmi Fadhilah, Edhyana Sahiratmadja, Ani Melani Maskoen, Ratu Safitri, Supartini Syarif, Herman Susanto

Abstract:

Cervical cancer is the second most common cancer in women after breast cancer. In Indonesia, the incidence of cervical cancer cases is estimated at 25-40 per 100,000 women per year. Human papillomavirus (HPV) infection is a major cause of cervical cancer, and HPV-16 is the most common genotype that infects the cervical tissue. The major late protein L1 may be associated with infectivity and pathogenicity and its variation can be used to classify HPV isolates. The aim of this study was to determine the phylogenetic tree of HPV 16 L1 gene from cervical cancer patient isolates in Bandung. After confirming HPV-16 by Linear Array Genotyping Test, L1 gene was amplified using specific primers and subject for sequencing. Phylogenetic analysis revealed that HPV 16 from Bandung was in the subgroup of Asia and East Asia, showing the close host-agent relationship among the Asian type.

Keywords: L1 HPV 16, cervical cancer, bandung, phylogenetic

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5157 Real-Time Quantitative Polymerase Chain Reaction Assay for the Detection of microRNAs Using Bi-Directional Extension Sequences

Authors: Kyung Jin Kim, Jiwon Kwak, Jae-Hoon Lee, Soo Suk Lee

Abstract:

MicroRNAs (miRNA) are a class of endogenous, single-stranded, small, and non-protein coding RNA molecules typically 20-25 nucleotides long. They are thought to regulate the expression of other genes in a broad range by binding to 3’- untranslated regions (3’-UTRs) of specific mRNAs. The detection of miRNAs is very important for understanding of the function of these molecules and in the diagnosis of variety of human diseases. However, detection of miRNAs is very challenging because of their short length and high sequence similarities within miRNA families. So, a simple-to-use, low-cost, and highly sensitive method for the detection of miRNAs is desirable. In this study, we demonstrate a novel bi-directional extension (BDE) assay. In the first step, a specific linear RT primer is hybridized to 6-10 base pairs from the 3’-end of a target miRNA molecule and then reverse transcribed to generate a cDNA strand. After reverse transcription, the cDNA was hybridized to the 3’-end which is BDE sequence; it played role as the PCR template. The PCR template was amplified in an SYBR green-based quantitative real-time PCR. To prove the concept, we used human brain total RNA. It could be detected quantitatively in the range of seven orders of magnitude with excellent linearity and reproducibility. To evaluate the performance of BDE assay, we contrasted sensitivity and specificity of the BDE assay against a commercially available poly (A) tailing method using miRNAs for let-7e extracted from A549 human epithelial lung cancer cells. The BDE assay displayed good performance compared with a poly (A) tailing method in terms of specificity and sensitivity; the CT values differed by 2.5 and the melting curve showed a sharper than poly (A) tailing methods. We have demonstrated an innovative, cost-effective BDE assay that allows improved sensitivity and specificity in detection of miRNAs. Dynamic range of the SYBR green-based RT-qPCR for miR-145 could be represented quantitatively over a range of 7 orders of magnitude from 0.1 pg to 1.0 μg of human brain total RNA. Finally, the BDE assay for detection of miRNA species such as let-7e shows good performance compared with a poly (A) tailing method in terms of specificity and sensitivity. Thus BDE proves a simple, low cost, and highly sensitive assay for various miRNAs and should provide significant contributions in research on miRNA biology and application of disease diagnostics with miRNAs as targets.

Keywords: bi-directional extension (BDE), microRNA (miRNA), poly (A) tailing assay, reverse transcription, RT-qPCR

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5156 Role of Molecular Changes and Immunohistochemical in Early Detection of Liver Cancer

Authors: Fatimah A. Alhomaid

Abstract:

The present study was planned to investigate the role of molecular changes and immunohistochemical in early detection of liver cancer in Saudi patients. our results were carried out on 54 patients liver cancer. We obtained our data from laboratory in King Khalid University Hospital. The specimens were taken (54) patients with liver cancer 34 male and 14 female and 2 control. The average age of varied from 37-85 years. The tumor was diagnosed as grade I in tow patients (male and female) and grade 2 in 45 patients (28 male and 17 female) while the grade 3 in 4 patients (all males). The specimens were processed for haematoxylin and eosin staining, immunohistochemical technique and flow cytometry analysis. Our study noted that most patients had adenocarcinoma which characterized by presence of signet-ring cells were very clear in advanced patients with adenocarcinoma. Our sections in adenocarcinoma in grade 2 and stage 3 had an increase in signet ring cells,an increase in the acini of glands and an increase in number of lymphocytes which spread to the muscular layer. With advancing the disease, there were haemorrhage in blood and increase in lymphocytes and increase in the number of nuclei in the tubular glands. Our study was carried on 48 patients, immunohistochemical diagnosis (CK20, PCNA, P53) and the analysis of DNA content by flow cytometry technique. Our study indicated that the presence of correlation between the immunohistochemical analysis for P53 and the grades. The reaction of P53 appeared as strong in nucleus in grades &stage 3 and appeared in other sections as dark brown pigment. Our study indicated that the absence of correlation between the immunohistochemical analysis for PCAN and the grades. In our sections there were strong reaction in the more 80% of nuclei in grade 1& stage 2. Our study indicated that the presence of correlation between the immunohistochemical analysis for CK20 and the grades. Our results indicated the presence of positive reaction in cytoplasm varied from weak to moderate in grade 3 & stage 4. Concerning the Flow cytometry technique our results indicated that the presence of correlation between the DNA and different stages of liver cancer.

Keywords: cancer, CK20, DNA, cytometry analysis, liver, immunohistochemical, molecular changes, PCNA, p53

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5155 Treatment of Histopathological Symptoms in N-Nitrosopyrrolidine Induced Changes in Lung Tissue by Isolated Flavonoid from Indigofera tinctoria

Authors: Aastha Agarwal, Veena Sharma

Abstract:

N-nitrosopyrollidine or NPYR is a tobacco-specific nitrosamine which upon intoxicated causes abnormal production of Reactive Oxygen Species disrupt the endogenous antioxidant system. The study was designed to evaluate the histological changes in lung tissue of Mus musculus in NPYR administered lungs and effect of isolated flavonoid 3,6-dihydroxy-(3’,4’,7’-trimethoxyphenyl)-chromen-4-one-7-glucoside (ITC) from experimental plant Indigofera tinctorial. Post treatment with isolated compound significantly restored the abnormal symptoms and changes in pulmonary tissue. Transverse section of mouse lung in control animals appeared as a thin lace. Histologically, most of the lung was arranged as alveoli which were thin walled structures made up of single layered squamous epithelial cells. In the transverse section of lung at 100 X will clearly show the component of alveoli, surround by a thin layer of connective tissue and blood vessels. Smaller bronchioles were lined by cuboidal epithelial cells while larger bronchioles were lined by ciliated columnar epithelium layer while in NPYR intoxicated lungs signs of vast pulmonary damages and carcinogenesis as alveolar damage, necrosis, DADs or defused alveolar damages hyperplasia, metaplasia, dysplasia and next stage of carcinogenesis were revealed. Treatment with ITC showed the significant positive changes in the lung tissue due to the side hydroxyl and methoxy groups in its structure which help in combating oxidative injuries and give protection from the free radicals generated during the metabolism of NPYR in body. Thus, histopathological analysis confirms the development of the cancerous conditions in the lung tissue in mice model and the protective effects of ITC.

Keywords: flavonoid, histopathology, Indigofera tinctoria, lung

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5154 Efficient Signal Detection Using QRD-M Based on Channel Condition in MIMO-OFDM System

Authors: Jae-Jeong Kim, Ki-Ro Kim, Hyoung-Kyu Song

Abstract:

In this paper, we propose an efficient signal detector that switches M parameter of QRD-M detection scheme is proposed for MIMO-OFDM system. The proposed detection scheme calculates the threshold by 1-norm condition number and then switches M parameter of QRD-M detection scheme according to channel information. If channel condition is bad, the parameter M is set to high value to increase the accuracy of detection. If channel condition is good, the parameter M is set to low value to reduce complexity of detection. Therefore, the proposed detection scheme has better trade off between BER performance and complexity than the conventional detection scheme. The simulation result shows that the complexity of proposed detection scheme is lower than QRD-M detection scheme with similar BER performance.

Keywords: MIMO-OFDM, QRD-M, channel condition, BER

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5153 Relationship of Epidermal Growth Factor Receptor Gene Mutations Andserum Levels of Ligands in Non-Small Cell Lung Carcinoma Patients

Authors: Abdolamir Allameh, Seyyed Mortaza Haghgoo, Adnan Khosravi, Esmaeil Mortaz, Mihan Pourabdollah-Toutkaboni, Sharareh Seifi

Abstract:

Non-Small Cell Lung Carcinoma (NSCLC) is associated with a number of gene mutations in epidermal growth factor receptor (EGFR). The prognostic significance of mutations in exons 19 and 21, together with serum levels of EGFR, amphiregulin (AR), and Transforming Growth Factor-alpha (TGF-α) are implicated in diagnosis and treatment. The aim of this study was to examine the relationship of EGFR mutations in selected exons with the expression of relevant ligands in sera samples of NSCLC patients. For this, a group of NSCLC patients (n=98) referred to the hospital for lung surgery with a mean age of 59±10.5 were enrolled (M/F: 75/23). Blood specimen was collected from each patient. Besides, formalin fixed paraffin embedded tissues were processed for DNA extraction. Gene mutations in exons 19 and 21 were detected by direct sequencing, following DNA amplification which was done by PCR (Polymerase Chain Reaction). Also, serum levels of EGFR, AR, and TGF-α were measured by ELISA. The results of our study show that EGFR mutations were present in 37% of Iranian NSCLC patients. The most frequently identified mutations were deletions in exon 19 (72.2%) and substitutions in exon 21 (27.8%). The most frequently identified alteration, which is considered as a rare mutation, was the E872K mutation in exon 21, which was found in 90% (9 out of 10) cases. EGFR mutation detected in exon 21 was significantly (P<0.05) correlated with the levels of its ligands, EGFR and TGF-α in serum samples. Furthermore, it was found that increased serum AR (>3pg/ml) and TGF-α (>10.5 pg/ml) were associated with shorter overall survival (P<0.05). The results clearly showed a close relationship between EGFR mutations and serum EGFR and serum TGF-α. Increased serum EGFR was associated with TGF-α and AR and linked to poor prognosis of NSCLC. These findings are implicated in clinical decision-making related to EGFR-Tyrosine kinase inhibitors (TKIs).

Keywords: lung cancer, Iranian patients, epidermal growth factor, mutation, prognosis

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5152 The Nurse Practitioner’s Role Functions in Multi-Specialist Team When Caring for a Metastatic Colon Cancer Patient with Acute Intestinal Obstruction

Authors: Yun-Tsuen Chen, Shih-Ting Huang, Pi-Fen Cheng, Yu-Ting Su, Joffrey Hsu, Hui-Zhu Chen

Abstract:

Acute intestinal obstruction is one of the differentials of acute abdomen and requires timely alleviation of intestinal distention and abdominal pain to avoid perforation, intra-abdominal infection, and peritonitis. Investigation to identify the cause of obstruction will direct treatment planning and allow for more effective management. In this study, we present a 71-year-old female presenting with symptoms of acute intestinal obstruction for five days. After extensive history taking, physical exam, medical imaging, and pathology, the patient was diagnosed with colon cancer with lung metastasis and acute intestinal obstruction. The patient was placed on nil per os status with intravenous fluid support, intravenous antibiotics, and a decompression nasogastric tube was placed. The patient received decompression with colostomy creation surgery. After assessing the patient’s clinical condition and tumor staging, a multidisciplinary healthcare team created an individualized treatment plan, which included plans to prepare the patient for home self-care and maintain good mental health with regular monitoring in the clinic setting. This case demonstrates the importance of early diagnosis, effective treatment, and a multidisciplinary approach to the management of acute intestinal obstruction secondary to colon cancer.

Keywords: acute intestinal obstruction, colostomy surgery, metastatic colon cancer, multidisciplinary healthcare team

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5151 Pathomorphological Features of Lungs from Brown Hares Infected with Parasites

Authors: Mariana Panayotova-Pencheva, Anetka Trifonova, Vassilena Dakova

Abstract:

790 lungs from brown hares (Lepus europeus L.) from different regions of Bulgaria were investigated during the period 2009-2017. The parasitological status and pathomorphological features in the lungs were recorded. The following parasite species were established: one nematode - Protostrongylus tauricus (7.59% prevalence), one tapeworm – larva of Taenia pisiformis Cysticercus pisiformis (3.04% prevalence) and one arthropod – larva of Linguatula serrata – Pentastomum dentatum (0.89% prevalence). Macroscopic lesions in the lungs were different depending on the causative agents. The infections with C. pisiformis and P. dentatum were attended with small, mainly superficial changes in the lungs. Protostrongylid infections were connected with different in appearance and burden macroscopic changes. In 77.7%, they were nodular, and in the rest of cases, they diffuse. The consistency of the lesions was compact. In most of the cases, alterations were grey in colour, rarely were dark-red or marble-like. In 91.7% of these cases, they were spread on the apical parts of large lung lobes. In 36.7% middle parts of the large lung lobes, and, in 26.7% small lung lobes, were also affected. The small lung lobes were never independently infected.

Keywords: Cysticercus pisiformis, Lepus europeus, lung lesions, Pentastomum dentatum, Protostrongylus tauricus

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5150 Adverse Reactions from Contrast Media in Patients Undergone Computed Tomography at the Department of Radiology, Srinagarind Hospital

Authors: Pranee Suecharoen, Jaturat Kanpittaya

Abstract:

Background: The incidence of adverse reactions to iodinated contrast media has risen. The dearth of reports on reactions to the administration of iso- and low-osmolar contrast media should be addressed. We, therefore, studied the profile of adverse reactions to iodinated contrast media; viz., (a) the body systems affected (b) causality, (c) severity, and (d) preventability. Objective: To study adverse reactions (causes and severity) to iodinated contrast media at Srinagarind Hospital. Method: Between March and July, 2015, 1,101 patients from the Department of Radiology were observed and interviewed for the occurrence of adverse reactions. The patients were classified per Naranjo’s algorithm and through use of an adverse reactions questionnaire. Results: A total of 105 cases (9.5%) reported adverse reactions (57% male; 43% female); among whom 2% were iso-osmolar vs. 98% low-osmolar. Diagnoses included hepatoma and cholangiocarcinoma (24.8%), colorectal cancer (9.5%), breast cancer (5.7%), cervical cancer (3.8%), lung cancer (2.9%), bone cancer (1.9%), and others (51.5%). Underlying diseases included hypertension and diabetes mellitus type 2. Mild, moderate, and severe adverse reactions accounted for 92, 5 and 3%, respectively. The respective groups of escalating symptoms included (a) mild urticaria, itching, rash, nausea, vomiting, dizziness, and headache; (b) moderate hypertension, hypotension, dyspnea, tachycardia and bronchospasm; and (c) severe laryngeal edema, profound hypotension, and convulsions. All reactions could be anticipated per Naranjo’s algorithm. Conclusion: Mild to moderate adverse reactions to low-osmolar contrast media were most common and these occurred immediately after administration. For patient safety and better outcomes, improving the identification of patients likely to have an adverse reaction is essential.

Keywords: adverse reactions, contrast media, computed tomography, iodinated contrast agents

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5149 Reduced Complexity of ML Detection Combined with DFE

Authors: Jae-Hyun Ro, Yong-Jun Kim, Chang-Bin Ha, Hyoung-Kyu Song

Abstract:

In multiple input multiple output-orthogonal frequency division multiplexing (MIMO-OFDM) systems, many detection schemes have been developed to improve the error performance and to reduce the complexity. Maximum likelihood (ML) detection has optimal error performance but it has very high complexity. Thus, this paper proposes reduced complexity of ML detection combined with decision feedback equalizer (DFE). The error performance of the proposed detection scheme is higher than the conventional DFE. But the complexity of the proposed scheme is lower than the conventional ML detection.

Keywords: detection, DFE, MIMO-OFDM, ML

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5148 Development of an Electrochemical Aptasensor for the Detection of Human Osteopontin Protein

Authors: Sofia G. Meirinho, Luis G. Dias, António M. Peres, Lígia R. Rodrigues

Abstract:

The emerging development of electrochemical aptasen sors has enabled the easy and fast detection of protein biomarkers in standard and real samples. Biomarkers are produced by body organs or tumours and provide a measure of antigens on cell surfaces. When detected in high amounts in blood, they can be suggestive of tumour activity. These biomarkers are more often used to evaluate treatment effects or to assess the potential for metastatic disease in patients with established disease. Osteopontin (OPN) is a protein found in all body fluids and constitutes a possible biomarker because its overexpression has been related with breast cancer evolution and metastasis. Currently, biomarkers are commonly used for the development of diagnostic methods, allowing the detection of the disease in its initial stages. A previously described RNA aptamer was used in the current work to develop a simple and sensitive electrochemical aptasensor with high affinity for human OPN. The RNA aptamer was biotinylated and immobilized on a gold electrode by avidin-biotin interaction. The electrochemical signal generated from the aptamer–target molecule interaction was monitored electrochemically using cyclic voltammetry in the presence of [Fe (CN) 6]−3/− as a redox probe. The signal observed showed a current decrease due to the binding of OPN. The preliminary results showed that this aptasensor enables the detection of OPN in standard solutions, showing good selectivity towards the target in the presence of others interfering proteins such as bovine OPN and bovine serum albumin. The results gathered in the current work suggest that the proposed electrochemical aptasensor is a simple and sensitive detection tool for human OPN and so, may have future applications in cancer disease monitoring.

Keywords: osteopontin, aptamer, aptasensor, screen-printed electrode, cyclic voltammetry

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5147 Pre-Processing of Ultrasonography Image Quality Improvement in Cases of Cervical Cancer Using Image Enhancement

Authors: Retno Supriyanti, Teguh Budiono, Yogi Ramadhani, Haris B. Widodo, Arwita Mulyawati

Abstract:

Cervical cancer is the leading cause of mortality in cancer-related diseases. In this diagnosis doctors usually perform several tests to determine the presence of cervical cancer in a patient. However, these checks require support equipment to get the results in more detail. One is by using ultrasonography. However, for the developing countries most of the existing ultrasonography has a low resolution. The goal of this research is to obtain abnormalities on low-resolution ultrasound images especially for cervical cancer case. In this paper, we emphasize our work to use Image Enhancement for pre-processing image quality improvement. The result shows that pre-processing stage is promising to support further analysis.

Keywords: cervical cancer, mortality, low-resolution, image enhancement.

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5146 Discovery, Design and Synthesis of Some Novel Antitumor 1,2,4-Triazine Derivatives as C-Met Kinase Inhibitors

Authors: Ibrahim M. Labouta, Marwa H. El-Wakil, Hayam M. Ashour, Ahmed M. Hassan, Manal N. Saudi

Abstract:

The receptor tyrosine kinase c-Met is an attractive target for therapeutic treatment of cancers nowadays. Among the wide variety of heterocycles that have been explored for developing c-Met kinase inhibitors, the 1,2,4-triazines have been rarely investigated, although they are well known in the literature to possess antitumor activities. Herein we describe the design and synthesis of a novel series of 1,2,4-triazine derivatives possessing N-acylarylhydrazone moiety and another series combining the 1,2,4-triazine scaffold to the well-known anticancer drug 6-MP in order to explore their “double-drug” effect. The synthesized compounds were evaluated for their in vitro antitumor activity against three c-Met addicted cancer cell lines (A549, HT-29 and MKN-45). Most compounds showed moderate to excellent antiproliferative activity and four compounds showed potent inhibitory activity more than the reference drug Foretinib against one or more cancer cell lines. The obtained results revealed that the potent compounds are highly selective to A549 (lung adenocarcinoma) cancer cell line. The c-Met kinase inhibitory activity of the potent derivatives is still under investigation. The present study clearly demonstrates that the 1,2,4-triazine core ring exhibits promising antitumor activity with potential c-Met kinase inhibitory activity.

Keywords: 1, 2, 4-triazine, antitumor, c-Met inhibitor, double-drug

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5145 The Model Development of Caregiver Skills for the End of Life’s Cancer Patients

Authors: Chaliya Wamaloon, Malee Chaisaena, Nusara Prasertsri

Abstract:

Informal caregivers providing home-based palliative and end-of-life (EOL) care to people with advanced cancer is needed, however, there has not been develop caregiver skills for the EOL in cancer patients. The aim of this research was to study the model development of caregiver skills for the EOL in cancer patients. Mixed methods research was conducted in 3 phases. All subjects were in Ubon Rathchathani Cancer Hospital including 30 EOL cancer patient caregivers, 30 EOL cancer patients, and 111 health care professionals who provided care for the EOL cancer patients and 30 EOL target participants who had been trained to be cancer patient caregivers. The research tools were questionnaires, semi structured interviews, and caregiver skills questionnaires. Data were analyzed by using percentage, mean, standard deviation, pair t-test, and content analysis. The result from this study showed the model development of caregiver skills for cancer patients consisted of 9 domains skills: 1. monitoring, 2. interpreting, 3. making decisions, 4. taking action, 5. making adjustments, 6. providing hands-on care, 7. accessing resources, 8. working together with the ill patients, and 9. navigating the healthcare system. The model composed of skills development curriculum for cancer patient caregivers, Manual of palliative care for caregivers, diary of health care records for cancer patients, and the evaluation model of development of caregiver skills for EOL cancer patients. The results of the evaluation in the development model of caregiver skills for EOL cancer patients showed that the caregivers were satisfied with the model of development for caregiver skills at a high level. The comparison of the caregiver skills before and after obtaining the development of caregivers skills revealed that it improved at a statistically significant level (p < 0.05).

Keywords: caregiver, caregiver skills, cancer patients, end of life

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5144 Exploring the Relationship Between Helicobacter Pylori Infection and the Incidence of Bronchogenic Carcinoma

Authors: Jose R. Garcia, Lexi Frankel, Amalia Ardeljan, Sergio Medina, Ali Yasback, Omar Rashid

Abstract:

Background: Helicobacter pylori (H. pylori) is a gram-negative, spiral-shaped bacterium that affects nearly half of the population worldwide and humans serve as the principal reservoir. Infection rates usually follow an inverse relationship with hygiene practices and are higher in developing countries than developed countries. Incidence varies significantly by geographic area, race, ethnicity, age, and socioeconomic status. H. pylori is primarily associated with conditions of the gastrointestinal tract such as atrophic gastritis and duodenal peptic ulcers. Infection is also associated with an increased risk of carcinogenesis as there is evidence to show that H. pylori infection may lead to gastric adenocarcinoma and mucosa-associated lymphoid tissue (MALT) lymphoma. It is suggested that H. pylori infection may be considered as a systemic condition, leading to various novel associations with several different neoplasms such as colorectal cancer, pancreatic cancer, and lung cancer, although further research is needed. Emerging evidence suggests that H. pylori infection may offer protective effects against Mycobacterium tuberculosis as a result of non-specific induction of interferon- γ (IFN- γ). Similar methods of enhanced immunity may affect the development of bronchogenic carcinoma due to the antiproliferative, pro-apoptotic and cytostatic functions of IFN- γ. The purpose of this study was to evaluate the correlation between Helicobacter pylori infection and the incidence of bronchogenic carcinoma. Methods: The data was provided by a Health Insurance Portability and Accountability Act (HIPAA) compliant national database to evaluate the patients infected versus patients not infected with H. pylori using ICD-10 and ICD-9 codes. Access to the database was granted by the Holy Cross Health, Fort Lauderdale for the purpose of academic research. Standard statistical methods were used. Results:-Between January 2010 and December 2019, the query was analyzed and resulted in 163,224 in both the infected and control group, respectively. The two groups were matched by age range and CCI score. The incidence of bronchogenic carcinoma was 1.853% with 3,024 patients in the H. pylori group compared to 4.785% with 7,810 patients in the control group. The difference was statistically significant (p < 2.22x10-16) with an odds ratio of 0.367 (0.353 - 0.383) with a confidence interval of 95%. The two groups were matched by treatment and incidence of cancer, which resulted in a total of 101,739 patients analyzed after this match. The incidence of bronchogenic carcinoma was 1.929% with 1,962 patients in the H. pylori and treatment group compared to 4.618% with 4,698 patients in the control group with treatment. The difference was statistically significant (p < 2.22x10-16) with an odds ratio of 0.403 (0.383 - 0.425) with a confidence interval of 95%.

Keywords: bronchogenic carcinoma, helicobacter pylori, lung cancer, pathogen-associated molecular patterns

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5143 Possible Protective Role of Angiotensin II Antagonist on Bacterial Endotoxin Induced Acute Lung Injury: Morphological Study on Adult Male Albino Rat

Authors: Mohamed Bakry Mohamed Ali, Mohamed Ehab El-Din Mustafa, Joseph Naiem Sabet Aziz, Sarah Mahmoud Ali Kaooh

Abstract:

Background: Acute lung injury (ALI) is one of the major challenges in intensive care medicine. The most common extrapulmonary cause of ALI is sepsis, accounting more than 30% of the cases in humans. Lipopolysaccharide (LPS) has gained wide acceptance as a clinically relevant model of ALI. Lipopolysaccharide is a glycoprotein forming the major constituent of bacterial endotoxin. Losartan is angiotensin II type 1 (AT1) receptor antagonists. It is widely used for management of hypertension. It was recently suggested that losartan protects against septic ALI. It would thereby prevent LPS-induced ALI. Aim of the work and design of the experiment: This work investigated the injurious effect of lipopolysaccharide (LPS) and ALI on adult male albino rat at 24 hours and 14 days of LPS administration and the possible protective role of losartan pretreatment. LPS has deteriorated animal survival and behavior. It increased lung weight and induced lung histological damage. These changes could be much reduced by the losartan pretreatment. Conclusion: Administration of losartan before LPS could largely reduce these LPS/ ALI induced short and long term alterations. It could be recommended that patients susceptible to developing ALI, as in ICU, should receive a protective dose of angitensin II type 1 (AT1) receptor blocker as losartan.

Keywords: acute lung injury (ALI), lipopolysaccharide (LPS), losartan

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5142 Prevalence and Correlates of Anxiety and Depression among Family Carers of Cancer

Authors: Godfrey Katende, Lillian Nakimera

Abstract:

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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5141 MTT Assay-Guided Isolation of a Cytotoxic Lead from Hedyotis umbellata and Its Mechanism of Action against Non-Small Cell Lung Cancer A549 Cells

Authors: Kirti Hira, A. Sajeli Begum, S. Mahibalan, Poorna Chandra Rao

Abstract:

Introduction: Cancer is one of the leading causes of death worldwide. Although existing therapy effectively kills cancer cells, they do affect normal growing cells leading to many undesirable side effects. Hence there is need to develop effective as well as safe drug molecules to combat cancer, which is possible through phyto-research. The currently available plant-derived blockbuster drugs are the example for this. In view of this, an investigation was done to identify cytotoxic lead molecules from Hedyotis umbellata (Family Rubiaceae), a widely distributed weed in India. Materials and Methods: The methanolic extract of the whole plant of H. umbellata (MHU), prepared through Soxhlet extraction method was further fractionated with diethyl ether and n-butanol, successively. MHU, ether fraction (EMHU) and butanol fraction (BMHU) were lyophilized and were tested for the cytotoxic effect using 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay against non-small cell lung cancer (NSCLC) A549 cell lines. The potentially active EMHU was subjected to chromatographic purification using normal-phase silica columns, in order to isolate the responsible bioactive compounds. The isolated pure compounds were tested for their cytotoxic effect by MTT assay against A549 cells. Compound-3, which was found to be most active, was characterized using IR, 1H- and 13C-NMR and MS analysis. The study was further extended to decipher the mechanism of action of cytotoxicity of compound-3 against A549 cells through various in vitro cellular models. Cell cycle analysis was done using flow cytometry following PI (Propidium Iodide) staining. Protein analysis was done using Western blot technique. Results: Among MHU, EMHU, and BMHU, the non-polar fraction EMHU demonstrated a significant dose-dependent cytotoxic effect with IC50 of 67.7μg/ml. Chromatography of EMHU yielded seven compounds. MTT assay of isolated compounds explored compound-3 as potentially active one, which inhibited the growth of A549 cells with IC50value of 14.2μM. Further, compound-3 was identified as cedrelopsin, a coumarin derivative having molecular weight of 260. Results of in vitro mechanistic studies explained that cedrelopsin induced cell cycle arrest at G2/M phase and down-regulated the expression of G2/M regulatory proteins such as cyclin B1, cdc2, and cdc25C, dose dependently. This is the first report that explores the cytotoxic mechanism of cedrelopsin. Conclusion: Thus a potential small lead molecule, cedrelopsin isolated from H. umbellata, showing antiproliferative effect mediated by G2/M arrest in A549 cells was discovered. The effect of cedrelopsin against other cancer cell lines followed by in vivo studies can be performed in future to develop a new drug candidate.

Keywords: A549, cedrelopsin, G2/M phase, Hedyotis umbellata

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5140 An Alternative Nano Design Strategy by Neutralized AMPS and Soy Bean Lecithin to Form Nanoparticles

Authors: Esra Cansever Mutlu, Muge Sennaroglu Bostan, Fatemeh Bahadori, Ebru Toksoy Oner, Mehmet S. Eroglu

Abstract:

Paclitaxel is used in treatment of different cancer types mainly breast, ovarian, lung and Kaposi’s sarcoma. It is poorly soluble in water; therefore, currently used formulations tremendously show side-effects and high toxicity. Encapsulation of the drug in a nano drug carrier which causes both reducing side effects and increasing drug activity is a desired new approach for the nano-medicine to target the site of cancer. In this study, synthesis of a novel nano paclitaxel formulation made of a new amphiphilic monomer was followed by the investigation of its pharmacological properties. UV radical polymerization was carried out by using the monomer Lecithin-2-Acrylamido-2-methylpropane (L-AMPS) and the drug-spacer, to obtain sterically high stabilized, biocompatible and biodegradable phospholipid nanoparticles, in which the drug paclitaxel (Pxl) was encapsulated (NanoPxl). Particles showed high drug loading capacity (68%) and also hydrodynamic size less than 200 nm with slight negative surface charge. The drug release profile was obtained and in vitro cytotoxicity test was performed on MCF-7 cell line. Consequently, these data indicated that paclitaxel loaded Lecithin-AMPS/PCL-MAC nanoparticles can be considered as a new, safe and effective nanocarrier for the treatment of breast cancer.

Keywords: paclitaxel, nanoparticle, drug delivery, L-AMPS

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5139 Cancer and Disability: A Psychosocial Approach in Puerto Rican Women as Cancer Survivors

Authors: Hector Jose Velazquez-Gonzalez, Norma Maldonado-Santiago, Laura Pietri-Gomez

Abstract:

Cancer is one of the first cause of death in the world, most of them are women. In Puerto Rico, there is a permanent controversy on the conceptuation of what really involves a disability, also in when a chronic illness, like cancer, should be considered a disability. The aim of the research was to identify functional limitation in 50 women survivors of cancer. In turn, to know the meanings that 6 women attributed to cancer with a focus on functionality. We conducted a mix method research based on surveys and narratives. We administered the World Health Organization Disability Assessment, version 2.0, which obtained a Cronbach’s alpha of .949 on the general scale, and from .773 to .956 on the six domains. The domain that obtained the highest average was social participation (M= 33.89, SD= 20.434), but it was not significant in the disability percentage. Also, there was no significance in the disability percentage in the other five domains. In a matter of meanings, we conduct a semistructured interview to 6 participants. All of them do not refer to cancer as a disability, either they do not know that in Puerto Rico cancer is considered as a disability by the law. However, participants agree that cancer at the time of treatment and subsequent to it, has significant effects on functional limitations (fatigue, pain, cognitive limitations, and weakness, among others. Psychooncologic practice should encourage the constant assessment of the functionality to identify the needs that emerge from oncological diagnosis. So that psychosocial intervention could be considered as critical in cancer treatment to promote a better quality of life and well-being in a person with cancer.

Keywords: cancer, Puerto Rico, disability, psychosocial approach

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5138 The Pressure Losses in the Model of Human Lungs

Authors: Michaela Chovancova, Pavel Niedoba

Abstract:

For the treatment of acute and chronic lung diseases it is preferred to deliver medicaments by inhalation. The drug is delivered directly to tracheobronchial tree. This way allows the given medicament to get directly into the place of action and it makes rapid onset of action and maximum efficiency. The transport of aerosol particles in the particular part of the lung is influenced by their size, anatomy of the lungs, breathing pattern and airway resistance. This article deals with calculation of airway resistance in the lung model of Horsfield. It solves the problem of determination of the pressure losses in bifurcation and thus defines the pressure drop at a given location in the bronchial tree. The obtained data will be used as boundary conditions for transport of aerosol particles in a central part of bronchial tree realized by Computational Fluid Dynamics (CFD) approach. The results obtained from CFD simulation will allow us to provide information on the required particle size and optimal inhalation technique for particle transport into particular part of the lung.

Keywords: human lungs, bronchial tree, pressure losses, airways resistance, flow, breathing

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5137 Cigarette Smoke Detection Based on YOLOV3

Authors: Wei Li, Tuo Yang

Abstract:

In order to satisfy the real-time and accurate requirements of cigarette smoke detection in complex scenes, a cigarette smoke detection technology based on the combination of deep learning and color features was proposed. Firstly, based on the color features of cigarette smoke, the suspicious cigarette smoke area in the image is extracted. Secondly, combined with the efficiency of cigarette smoke detection and the problem of network overfitting, a network model for cigarette smoke detection was designed according to YOLOV3 algorithm to reduce the false detection rate. The experimental results show that the method is feasible and effective, and the accuracy of cigarette smoke detection is up to 99.13%, which satisfies the requirements of real-time cigarette smoke detection in complex scenes.

Keywords: deep learning, computer vision, cigarette smoke detection, YOLOV3, color feature extraction

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5136 Knowledge and Attitude of Final Year Undergraduate Nursing Students towards Prevention of Cervical Cancer

Authors: Afaf Abdallah, Moawia Elsadig

Abstract:

Background: Cervical cancer is the second most common women cancer among worldwide; representing 13% of female cancers. In Sudan, it ranks as the second most frequent cancer among women as other developing countries. Aim: Is to study awareness, attitude of nursing students towards cervical cancer prevention. The results: Most of the students were not aware of other screening methods than Pap smear test. However, half of the respondents showed positive attitudes towards HPV vaccination. More than two-thirds of respondents exhibited a positive attitude and were willing to undergo Pap smear in the future. Conclusion: The study shows that the majority of the participants have poor information, education would motivate nurses to participate actively in awareness raising, screening, and management.

Keywords: cervical cancer, knowledge, attitude, screening

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5135 Antibody-Conjugated Nontoxic Arginine-Doped Fe3O4 Nanoparticles for Magnetic Circulating Tumor Cells Separation

Authors: F. Kashanian, M. M. Masoudi, A. Akbari, A. Shamloo, M. R. Zand, S. S. Salehi

Abstract:

Nano-sized materials present new opportunities in biology and medicine and they are used as biomedical tools for investigation, separation of molecules and cells. To achieve more effective cancer therapy, it is essential to select cancer cells exactly. This research suggests that using the antibody-functionalized nontoxic Arginine-doped magnetic nanoparticles (A-MNPs), has been prosperous in detection, capture, and magnetic separation of circulating tumor cells (CTCs) in tumor tissue. In this study, A-MNPs were synthesized via a simple precipitation reaction and directly immobilized Ep-CAM EBA-1 antibodies over superparamagnetic A-MNPs for Mucin BCA-225 in breast cancer cell. The samples were characterized by vibrating sample magnetometer (VSM), FT-IR spectroscopy, Tunneling Electron Microscopy (TEM) and Scanning Electron Microscopy (SEM). These antibody-functionalized nontoxic A-MNPs were used to capture breast cancer cell. Through employing a strong permanent magnet, the magnetic separation was achieved within a few seconds. Antibody-Conjugated nontoxic Arginine-doped Fe3O4 nanoparticles have the potential for the future study to capture CTCs which are released from tumor tissue and for drug delivery, and these results demonstrate that the antibody-conjugated A-MNPs can be used in magnetic hyperthermia techniques for cancer treatment.

Keywords: tumor tissue, antibody, magnetic nanoparticle, CTCs capturing

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5134 Toward Automatic Chest CT Image Segmentation

Authors: Angely Sim Jia Wun, Sasa Arsovski

Abstract:

Numerous studies have been conducted on the segmentation of medical images. Segmenting the lungs is one of the common research topics in those studies. Our research stemmed from the lack of solutions for automatic bone, airway, and vessel segmentation, despite the existence of multiple lung segmentation techniques. Consequently, currently, available software tools used for medical image segmentation do not provide automatic lung, bone, airway, and vessel segmentation. This paper presents segmentation techniques along with an interactive software tool architecture for segmenting bone, lung, airway, and vessel tissues. Additionally, we propose a method for creating binary masks from automatically generated segments. The key contribution of our approach is the technique for automatic image thresholding using adjustable Hounsfield values and binary mask extraction. Generated binary masks can be successfully used as a training dataset for deep-learning solutions in medical image segmentation. In this paper, we also examine the current software tools used for medical image segmentation, discuss our approach, and identify its advantages.

Keywords: lung segmentation, binary masks, U-Net, medical software tools

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5133 Upconversion Nanomaterials for Applications in Life Sciences and Medicine

Authors: Yong Zhang

Abstract:

Light has proven to be useful in a wide range of biomedical applications such as fluorescence imaging, photoacoustic imaging, optogenetics, photodynamic therapy, photothermal therapy, and light controlled drug/gene delivery. Taking photodynamic therapy (PDT) as an example, PDT has been proven clinically effective in early lung cancer, bladder cancer, head, and neck cancer and is the primary treatment for skin cancer as well. However, clinical use of PDT is severely constrained by the low penetration depth of visible light through thick tissue, limiting its use to target regions only a few millimeters deep. One way to enhance the range is to use invisible near-infrared (NIR) light within the optical window (700–1100nm) for biological tissues, extending the depth up to 1cm with no observable damage to the intervening tissue. We have demonstrated use of NIR-to-visible upconversion fluorescent nanoparticles (UCNPs), emitting visible fluorescence when excited by a NIR light at 980nm, as a nanotransducer for PDT to convert deep tissue-penetrating NIR light to visible light suitable for activating photosensitizers. The unique optical properties of UCNPs enable the upconversion wavelength to be tuned and matched to the activation absorption wavelength of the photosensitizer. At depths beyond 1cm, however, tissue remains inaccessible to light even within the NIR window, and this critical depth limitation renders existing phototherapy ineffective against most deep-seated cancers. We have demonstrated some new treatment modalities for deep-seated cancers based on UCNP hydrogel implants and miniaturized, wirelessly powered optoelectronic devices for light delivery to deep tissues.

Keywords: upconversion, fluorescent, nanoparticle, bioimaging, photodynamic therapy

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5132 The Effect of Diet Intervention for Breast Cancer: A Meta-Analysis

Authors: Bok Yae Chung, Eun Hee Oh

Abstract:

Breast cancer patients require more nutritional interventions than others. However, a few studies have attempted to assess the overall nutritional status, to reduce body weight and BMI by improving diet, and to improve the prognosis of cancer for breast cancer patients. The purpose of this study was to evaluate the effect of diet intervention in the breast cancer patients through meta-analysis. For the study purpose, 16 studies were selected by using PubMed, ScienceDirect, ProQuest and CINAHL. Meta-analysis was performed using a random-effects model, and the effect size on outcome variables in breast cancer was calculated. The effect size for outcome variables of diet intervention was a large effect size. For heterogeneity, moderator analysis was performed using intervention type and intervention duration. All moderators did not significant difference. Diet intervention has significant positive effects on outcome variables in breast cancer. As a result, it is suggested that the timing of the intervention should be no more than six months, but a strategy for sustaining long-term intervention effects should be added if nutritional intervention is to be administered for breast cancer patients in the future.

Keywords: breast cancer, diet, mete-analysis, intervention

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