Search results for: molecular mechanisms of cancer
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 6026

Search results for: molecular mechanisms of cancer

5846 Synthesis, Molecular Docking, and Cytotoxic Activity of Novel Triazolopyridazine Derivatives

Authors: Azza T. Tahera, Eman M. Ahmeda, Nadia A. Khalila, Yassin M. Nissanb

Abstract:

New 3-(pyridin-4-yl)-[1,2,4] triazolo [4,3-b] pyridazine derivatives 2a-i, 4a,b and 6a,b were designed, synthesized and evaluated as cytotoxic agents. All compounds were investigated for their in vitro cytotoxicity at a single dose 10-5M concentration towards 60 cancer cell lines according to USA NCI protocol. The preliminary screening results showed that the majority of tested compounds exhibited remarkable activity against SR (leukemia) cell panel. Molecular docking for all synthesized compounds was performed on the active site of c-Met kinase. The most active compounds, 2f and 4a were further evaluated at a seven dose level screening and their IC50 as a c-Met kinase inhibitors were determined in vitro.

Keywords: triazolopyridazines, pyridazines, cytotoxic activity, cell panel

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5845 Identification of Potential Small Molecule Inhibitors Against β-hCG for Cancer Therapy: An In-Silico Study

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

Abstract:

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

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

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5844 A Review of Effective Gene Selection Methods for Cancer Classification Using Microarray Gene Expression Profile

Authors: Hala Alshamlan, Ghada Badr, Yousef Alohali

Abstract:

Cancer is one of the dreadful diseases, which causes considerable death rate in humans. DNA microarray-based gene expression profiling has been emerged as an efficient technique for cancer classification, as well as for diagnosis, prognosis, and treatment purposes. In recent years, a DNA microarray technique has gained more attraction in both scientific and in industrial fields. It is important to determine the informative genes that cause cancer to improve early cancer diagnosis and to give effective chemotherapy treatment. In order to gain deep insight into the cancer classification problem, it is necessary to take a closer look at the proposed gene selection methods. We believe that they should be an integral preprocessing step for cancer classification. Furthermore, finding an accurate gene selection method is a very significant issue in a cancer classification area because it reduces the dimensionality of microarray dataset and selects informative genes. In this paper, we classify and review the state-of-art gene selection methods. We proceed by evaluating the performance of each gene selection approach based on their classification accuracy and number of informative genes. In our evaluation, we will use four benchmark microarray datasets for the cancer diagnosis (leukemia, colon, lung, and prostate). In addition, we compare the performance of gene selection method to investigate the effective gene selection method that has the ability to identify a small set of marker genes, and ensure high cancer classification accuracy. To the best of our knowledge, this is the first attempt to compare gene selection approaches for cancer classification using microarray gene expression profile.

Keywords: gene selection, feature selection, cancer classification, microarray, gene expression profile

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5843 Experienced Chronic Sorrow in Mothers of Children with Cancer: A Phenomenological Study

Authors: Nikfarid Lida, Maryam Rassouli, Leili Borimnejad, Hamid Alavi Majd

Abstract:

Purpose: Chronic sorrow is experienced by mothers of children with cancer. It is a multidimensional concept and is experienced by mothers in different ways depends on their various contexts. Little is known about the concept of chronic sorrow in mothers of children with cancer living in Iran. This study aimed to clarify the concept and explain lived experiences of chronic sorrow in Iranian mothers of children with cancer. Methods: In this hermeneutic phenomenological study, 8 mothers of children with cancer participated in semi structured in-depth interviews about their experiences of chronic sorrow. Interviews continued until data saturation was reached. All interviews were recorded, transcribed, analyzed, and interpreted using 7 steps of the Dickelman et al’s phenomenological approach. Results: Three main themes emerged from mothers’ experiences of chronic sorrow related to child’s cancer. These main themes were ‘climbing up shaky rocks,’ ‘fear and hope,’ and ‘continuous role changing.’ Each of these themes consisted of several subthemes. Conclusion: There are similarities in experiencing chronic sorrow by mothers of children with chronic diseases in different societies. However some experiences are unique in Iranian mothers of children with cancer.

Keywords: cancer, children, mothers, Iran, phenomenology

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5842 Using Econometric Methods to Explore Obesity Stigma and Avoidance of Breast and Cervical Cancer Screening

Authors: Stephanie A. Schauder, Gosia Sylwestrzak

Abstract:

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

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

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5841 Molecular Junctions between Graphene Strips: Electronic and Transport Properties

Authors: Adel Belayadi, Ahmed Mougari, Boualem Bourahla

Abstract:

Molecular junctions are currently considered a promising style in the miniaturization of electronic devices. In this contribution, we provide a tight-binding model to investigate the quantum transport properties across-molecular junctions sandwiched between 2D-graphene nanoribbons in the zigzag direction. We investigate, in particular, the effect of embedded atoms such as Gold and Silicon across the molecular junction. The results exhibit a resonance behavior in terms of incident Fermi levels, depending on the molecular junction type. Additionally, the transport properties under a perpendicular magnetic field exhibit an oscillation for the transmittance versus the magnetic field strength.

Keywords: molecular junction, 2D-graphene nanoribbons, quantum transport properties, magnetic field

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5840 Molecular Dynamic Simulation of Cold Spray Process

Authors: Aneesh Joshi, Sagil James

Abstract:

Cold Spray (CS) process is deposition of solid particles over a substrate above a certain critical impact velocity. Unlike thermal spray processes, CS process does not melt the particles thus retaining their original physical and chemical properties. These characteristics make CS process ideal for various engineering applications involving metals, polymers, ceramics and composites. The bonding mechanism involved in CS process is extremely complex considering the dynamic nature of the process. Though CS process offers great promise for several engineering applications, the realization of its full potential is limited by the lack of understanding of the complex mechanisms involved in this process and the effect of critical process parameters on the deposition efficiency. The goal of this research is to understand the complex nanoscale mechanisms involved in CS process. The study uses Molecular Dynamics (MD) simulation technique to understand the material deposition phenomenon during the CS process. Impact of a single crystalline copper nanoparticle on copper substrate is modelled under varying process conditions. The quantitative results of the impacts at different velocities, impact angle and size of the particles are evaluated using flattening ratio, von Mises stress distribution and local shear strain. The study finds that the flattening ratio and hence the quality of deposition was highest for an impact velocity of 700 m/s, particle size of 20 Å and an impact angle of 90°. The stress and strain analysis revealed regions of shear instabilities in the periphery of impact and also revealed plastic deformation of the particles after the impact. The results of this study can be used to augment our existing knowledge in the field of CS processes.

Keywords: cold spray process, molecular dynamics simulation, nanoparticles, particle impact

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5839 The impact of Breast Cancer Polymorphism on Breast Cancer

Authors: Roudabeh Vakil Monfared, Farhad Mashayekhi

Abstract:

Breast cancer is the most common malignancy type among women with about 1 million new cases each year. The immune system plays an important role in the breast cancer development. OX40L (also known as TNFSF4), a membrane protein, which is a member of the tumor necrosis factor super family binds to its receptor OX40 and this co-stimulation has a crucial role in T-cell proliferation, survival and cytokine release. Due to the importance of the T-cells in anti-tumor activities of OX40L we studied the association of rs3850641 (T→C) polymorphism of OX40L gene with breast cancer. The study included 123 women with breast cancer and 126 healthy volunteers with no signs of cancer. Genomic DNA was extracted from blood leucocytes. Genotype and allele frequencies were determined in patients and control cases with the method of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and the analysis was performed by Med Calc. The prevalence of genotype frequencies of TT, CT and CC were 60.9%, 30.08% and 8.9 % in patients with breast cancer and 74.6 %, 18.25 % and 7.14 % in healthy volunteers while the T and C allelic frequency was 76.01% and 23.98 % in patients and 83.73% and 16.26% in healthy controls. Respectively Statistical analysis has shown no significant difference from the comparison of either genotype (P=0.06). According to these results, the rs3850641 SNP has no association with the susceptibility of breast cancer in a population in northern Iran. However, further studies in larger populations including other genetic and environmental factors are required to achieve conclusion.

Keywords: OX40L, gene, polymorphism, breast cancer

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5838 Estimation of Serum Levels of Calcium and Inorganic Phosphorus in Breast Cancer Patients

Authors: Safa Safdar

Abstract:

Breast cancer is a type of cancer which is developed by the formation of a tumor on the breast. This tumor invades and causes different electrolyte imbalance. The present study was designed to measure the serum calcium and inorganic phosphorous levels and to check the frequency of hypercalcemia and hypophosphatemia in breast cancer patients. Serum calcium and phosphorous levels of fifty breast cancer women of 18-70 years of age group and fifty healthy women of same age group were measured by using semi-automated chemistry analyzer ( Humalyzer 3000, Human, Germany ). Significant variation in these levels was observed. The mean calcium value in BC patients was higher 9.398 mg/dl as compared to controls which were 8.694 mg/dl. Whereas the mean value of inorganic phosphorus level was lower 4.060 mg/dl in BC patients as compared to controls having 4.456 mg/dl. In this study, the frequency of hypercalcemia in Breast cancer patients was 10% i.e. only 10 out of 50 Breast cancer patients were suffering from hypercalcemia. Whereas the frequency of hypophosphatemia in this study was only 2 % i.e. only 1 out of 50 patients was suffering from hypophosphatemia. Thus it is concluded that there is a significant change in serum calcium and inorganic phosphorous levels in Breast cancer patients as the disease progresses. So, this study will be helpful for the clinicians to maintain serum calcium and phosphorous levels in Breast cancer patients and also preventing them from further complications.

Keywords: serum analysis, calcium, inorganic phosphorus, hpercalcemia hypophosphatemia

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5837 Malignancy in Venous Thromboembolism

Authors: Naser Shagerdi Esmaeli, Mohsen Hamidpour

Abstract:

Purposes: The activation of coagulation in patients with cancer contributes significantly to morbidity and mortality rates and may play a fundamental role in the host response to growing tumor’s. Patients with cancer are clearly at high risk for the development of venous thromboembolism (VTE), particularly during chemotherapy and surgery. This situation is aggravated by the use of venous access catheters and possibly growth factors. Methods: Data derived from large, randomized, controlled trials have been used to determine the true incidence of this complication of cancer and its treatment. The incidence based on the analyses of these randomized controlled trials varies from 1% for limited stage patients with breast cancer treated with tamoxifen to 60% for patients with any type of cancer who are subjected to orthopedic surgery and do not receive prophylactic therapy. Results: In view of the morbidity and mortality attributable to VTE in cancer, widespread utilization of prophylactic anticoagulation therapy, which has proven safe and effective in a variety of situations, should be considered. While migratory thrombophlebitis is a clear indicator of an underlying neoplasm, the risk of cancer in patients with the more typical form of VTE has been the subject of intense debate over recent years. Conclusion: Some investigators have suggested that the relative risk of being diagnosed with occult cancer within six months of an episode of VTE (particularly recurrent VTE) could be up to 10-fold. However, the cost-effectiveness of aggressive screening for cancer in patients with VTE has not yet been defined adequately.

Keywords: venous thromboembolism, malignancy, cancer, tumor, heparin

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5836 Antioxidants: Some Medicinal Plants in Indian System of Medicine Work as Anti-cervical Cancer

Authors: Kamini Kaushal

Abstract:

Medicinal plants of Ayurveda are effective in the treatment of cervical cancer. The aim of this paper is to assess anti cancerous activities of these medicinal plants against cancer. Most of the medicinal plants in Ayurveda are using to treat cervical cancer as name of disease as treatment of YONI VYAPADA. The selected plants has been studied scientifically in India and evidence based written since Vedic era. The compilation results showed potential anti cervical cancer activity of the tested plants. There plants are remaining under the dark due to lack of awareness, lack of popularity and barrier of language. Now this is the time to eye opener regarding the classical text and clinical evidences, so that we can give the hope to world's affected women from this disease. World is waiting for such type of remedy which is having zero side effects, low cost and effective.

Keywords: anti cancerous, cervical cancer, ayurveda, medicinal plants, scientific study, classical text

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5835 Identification of Disease Causing DNA Motifs in Human DNA Using Clustering Approach

Authors: G. Tamilpavai, C. Vishnuppriya

Abstract:

Studying DNA (deoxyribonucleic acid) sequence is useful in biological processes and it is applied in the fields such as diagnostic and forensic research. DNA is the hereditary information in human and almost all other organisms. It is passed to their generations. Earlier stage detection of defective DNA sequence may lead to many developments in the field of Bioinformatics. Nowadays various tedious techniques are used to identify defective DNA. The proposed work is to analyze and identify the cancer-causing DNA motif in a given sequence. Initially the human DNA sequence is separated as k-mers using k-mer separation rule. The separated k-mers are clustered using Self Organizing Map (SOM). Using Levenshtein distance measure, cancer associated DNA motif is identified from the k-mer clusters. Experimental results of this work indicate the presence or absence of cancer causing DNA motif. If the cancer associated DNA motif is found in DNA, it is declared as the cancer disease causing DNA sequence. Otherwise the input human DNA is declared as normal sequence. Finally, elapsed time is calculated for finding the presence of cancer causing DNA motif using clustering formation. It is compared with normal process of finding cancer causing DNA motif. Locating cancer associated motif is easier in cluster formation process than the other one. The proposed work will be an initiative aid for finding genetic disease related research.

Keywords: bioinformatics, cancer motif, DNA, k-mers, Levenshtein distance, SOM

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5834 Detection of Lymphedema after Breast Cancer in Yucatecan Women

Authors: Olais A. Ingrid, Peraza G. Leydi, Estrella C. Damaris

Abstract:

Breast cancer is the most common among women worldwide; the different treatments can bring sequels that directly affect the quality of life, such as lymphedema. The objective was to determine if there is presence of lymphedema secondary to breast cancer in Yucatecan women. It was an observational, analytical, cross-sectional study, 92 women were included who met the following criteria: women with surgical treatment for unilateral: breast cancer, aged between 25 and 65 years old, minimum 6 weeks after unilateral breast surgery and have completed any type of chemotherapy or adjuvant radiotherapy treatment for breast cancer. The evaluation was through indirect measurement volume by circometry to determine the presence of lymphedema. 23% of women had lymphedema grade I. It related to the presence of some of the symptoms like stiffness, swelling, decreased range of motion and feeling of heaviness in the arm of the operated side of the breast. It is important to determine the presence of lymphedema to perform physical therapy treatment.

Keywords: breast cancer, lymphedema, physical therapy, Yucatan

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5833 Induced Pluripotent Stem Cells-Derived Brain Organoids to Study the Mechanisms Underlying Disease Variability in Patients with SYNGAP1-Intelectual Disability

Authors: Aliyah Penn, Vasiliki Machairaki, Constance Smith-Hicks, Sarven Sabunciyan, Lena Smirnova

Abstract:

Rare neurodevelopmental disorders (RNDDs) encompass a spectrum of conditions affecting a minority of the global population yet pose significant challenges due to their heterogeneity and limited understanding. Among these disorders, SYNGAP1 mutations contribute to a range of cognitive impairments, autism spectrum disorder (ASD), and epilepsy. Despite its rarity, SYNGAP1-Intellectual Disability disorder manifests with varying severity, underscoring the need for improved insights into their underlying biological mechanisms. This research project aims to elucidate the molecular pathways driving the heterogeneous disease severity observed in individuals with SYNGAP1 mutations. Employing a multi-faceted approach, we first characterize SYNGAP1-induced pluripotent stem cells (iPSCs) and iPSC-derived brain organoids, comparing them with familial neurotypically-developed (NTD) controls. Subsequently, we identify molecular signatures of intellectual disability (ID) and epilepsy using RNA sequencing, shedding light on the pathological mechanisms underlying these conditions. Finally, we evaluate and establish a SYNGAP1 seizure model, leveraging MaxWell high-density micro-electrode array (HD-MEA) recordings to assess electrical activity and synaptic functions in SYNGAP-ID patients with different intensities of seizures. This comprehensive approach aims to enhance our understanding of SYNGAP1-related disorders and pave the way for personalized treatment strategies tailored to individual patients.

Keywords: SYNGAP, autism, organoids, neurodevelopment

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5832 Novel Molecular Mechanisms Involved in Macrophage Phenotypic Polarization

Authors: Mansi Srivastava, Uzma Saqib, Adnan Naim, Anjali Roy, Dongfang Liu, Deepak Bhatnagar, Ravinder Ravinder, Mirza S. Baig

Abstract:

Macrophages polarize to proinflammatory M1 or anti-inflammatory M2 states with distinct physiological functions. This transition within the M1 to M2 phenotypes decides the nature, duration, and severity of an inflammatory response. However, inspite of a substantial understanding of the fate of these phenotypes, the underlying molecular mechanisms are not well understood. We have investigated the role of Neuronal nitric oxide synthase (NOS1) mediated regulation of Activator protein 1 (AP-1) transcription factor in macrophages as a critical effector of macrophage phenotypic change. Activator protein 1 (AP-1) is a group of dimeric transcription factors composed of jun, Fos, and ATF family proteins. We determined that NOS1-derived nitric oxide (NO) facilitate Fos and jun interaction which induces IL12 & IL23 expression. Pharmacological inhibition of NOS1 inhibits Fos and jun interaction but increases ATF2 and Fos dimerization. Switching of Fos and jun dimer to ATF2 and jun dimerization switches phenotype from IL–12high IL-23high IL-10low to IL–12low IL-23lowIL-10high phenotype, respectively. Together, these findings highlight a key role of the TLR4-NOS1-AP1 signaling axis in regulating macrophage polarization.

Keywords: inflammation, macrophage, lipopolysaccharide (LPS), proinflammatory cytokines, activator protein 1 (AP-1), neuronal nitric oxide synthase (NOS1)

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5831 Survival Analysis of Identifying the Risk Factors of Affecting the First Recurrence Time of Breast Cancer: The Case of Tigray, Ethiopia

Authors: Segen Asayehegn

Abstract:

Introduction: In Tigray, Ethiopia, next to cervical cancer, breast cancer is one of the most common cancer health problems for women. Objectives: This article is proposed to identify the prospective and potential risk factors affecting the time-to-first-recurrence of breast cancer patients in Tigray, Ethiopia. Methods: The data were taken from the patient’s medical record that registered from January 2010 to January 2020. The study considered a sample size of 1842 breast cancer patients. Powerful non-parametric and parametric shared frailty survival regression models (FSRM) were applied, and model comparisons were performed. Results: Out of 1842 breast cancer patients, about 1290 (70.02%) recovered/cured the disease. The median cure time from breast cancer is found at 12.8 months. The model comparison suggested that the lognormal parametric shared a frailty survival regression model predicted that treatment, stage of breast cancer, smoking habit, and marital status significantly affects the first recurrence of breast cancer. Conclusion: Factors like treatment, stages of cancer, and marital status were improved while smoking habits worsened the time to cure breast cancer. Recommendation: Thus, the authors recommend reducing breast cancer health problems, the regional health sector facilities need to be improved. More importantly, concerned bodies and medical doctors should emphasize the identified factors during treatment. Furthermore, general awareness programs should be given to the community on the identified factors.

Keywords: acceleration factor, breast cancer, Ethiopia, shared frailty survival models, Tigray

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5830 Spectrophotometric Detection of Histidine Using Enzyme Reaction and Examination of Reaction Conditions

Authors: Akimitsu Kugimiya, Kouhei Iwato, Toru Saito, Jiro Kohda, Yasuhisa Nakano, Yu Takano

Abstract:

The measurement of amino acid content is reported to be useful for the diagnosis of several types of diseases, including lung cancer, gastric cancer, colorectal cancer, breast cancer, prostate cancer, and diabetes. The conventional detection methods for amino acid are high-performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometry (LC-MS), but they have several drawbacks as the equipment is cumbersome and the techniques are costly in terms of time and costs. In contrast, biosensors and biosensing methods provide more rapid and facile detection strategies that use simple equipment. The authors have reported a novel approach for the detection of each amino acid that involved the use of aminoacyl-tRNA synthetase (aaRS) as a molecular recognition element because aaRS is expected to a selective binding ability for corresponding amino acid. The consecutive enzymatic reactions used in this study are as follows: aaRS binds to its cognate amino acid and releases inorganic pyrophosphate. Hydrogen peroxide (H₂O₂) was produced by the enzyme reactions of inorganic pyrophosphatase and pyruvate oxidase. The Trinder’s reagent was added into the reaction mixture, and the absorbance change at 556 nm was measured using a microplate reader. In this study, an amino acid-sensing method using histidyl-tRNA synthetase (HisRS; histidine-specific aaRS) as molecular recognition element in combination with the Trinder’s reagent spectrophotometric method was developed. The quantitative performance and selectivity of the method were evaluated, and the optimal enzyme reaction and detection conditions were determined. The authors developed a simple and rapid method for detecting histidine with a combination of enzymatic reaction and spectrophotometric detection. In this study, HisRS was used to detect histidine, and the reaction and detection conditions were optimized for quantitation of these amino acids in the ranges of 1–100 µM histidine. The detection limits are sufficient to analyze these amino acids in biological fluids. This work was partly supported by Hiroshima City University Grant for Special Academic Research (General Studies).

Keywords: amino acid, aminoacyl-tRNA synthetase, biosensing, enzyme reaction

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5829 Managing Incomplete PSA Observations in Prostate Cancer Data: Key Strategies and Best Practices for Handling Loss to Follow-Up and Missing Data

Authors: Madiha Liaqat, Rehan Ahmed Khan, Shahid Kamal

Abstract:

Multiple imputation with delta adjustment is a versatile and transparent technique for addressing univariate missing data in the presence of various missing mechanisms. This approach allows for the exploration of sensitivity to the missing-at-random (MAR) assumption. In this review, we outline the delta-adjustment procedure and illustrate its application for assessing the sensitivity to deviations from the MAR assumption. By examining diverse missingness scenarios and conducting sensitivity analyses, we gain valuable insights into the implications of missing data on our analyses, enhancing the reliability of our study's conclusions. In our study, we focused on assessing logPSA, a continuous biomarker in incomplete prostate cancer data, to examine the robustness of conclusions against plausible departures from the MAR assumption. We introduced several approaches for conducting sensitivity analyses, illustrating their application within the pattern mixture model (PMM) under the delta adjustment framework. This proposed approach effectively handles missing data, particularly loss to follow-up.

Keywords: loss to follow-up, incomplete response, multiple imputation, sensitivity analysis, prostate cancer

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5828 Factors Contributing to Delayed Diagnosis and Treatment of Breast Cancer and Its Outcome in Jamhoriat Hospital Kabul, Afghanistan

Authors: Ahmad Jawad Fardin

Abstract:

Over 60% of patients with breast cancer in Afghanistan present late with advanced stage III and IV, a major cause for the poor survival rate. The objectives of this study were to identify the contributing factors for the diagnosis and treatment delay and its outcome. This cross-sectional study was conducted on 318 patients with histologically confirmed breast cancer in the oncology department of Jamhoriat hospital, which is the first and only national cancer center in Afghanistan; data were collected from medical records and interviews conducted with women diagnosed with breast cancer, linear regression and logistic regression were used for analysis. Patient delay was defined as the time from first recognition of symptoms until first medical consultation and doctor form first consultation with a health care provider until histological confirmation of breast cancer. The mean age of patients was 49.2+_ 11.5years. The average time for the final diagnosis of breast cancer was 8.5 months; most patients had ductal carcinoma 260.7 (82%). Factors associated with delay were low education level 76% poor socioeconomic and cultural conditions 81% lack of cancer center 73% lack of screening 19%. The stage distribution was as follows stage IV 4 22% stage III 44.4% stage II 29.3% stage I 4.3%. Complex associated factors were identified to delayed the diagnosis of breast cancer and increased adverse outcomes consequently. Raising awareness and education in women, the establishment of cancer centers and providing accessible diagnosis service and screening, training of general practitioners; required to promote early detection, diagnosis and treatment.

Keywords: delayed diagnosis and poor outcome, breast cancer in Afghanistan, poor outcome of delayed breast cancer treatment, breast cancer delayed diagnosis and treatment in Afghanistan

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5827 Higher Freshwater Fish and Sea Fish Intake Is Inversely Associated with Liver Cancer in Patients with Hepatitis B

Authors: Maomao Cao

Abstract:

Background and aims While the association between higher consumption of fish and lower liver cancer risk has been confirmed, however, the association between specific fish intake and liver cancer risk remains unknown. We aimed to identify the association between specific fish consumption and the risk of liver cancer. Methods: Based on a community-based seropositive hepatitis B cohort involving 18404 individuals, face to face interview was conducted by a standardized questionnaire to acquire baseline information. Three common fish types in this study were analyzed, including freshwater fish, sea fish, and small fish (shrimp, crab, conch, and shell). All participants received liver cancer screening, and possible cases were identified by CT or MRI. Multivariable logistic models were applied to estimate the odds ratio (OR) and 95% confidence intervals (CI). Multivariate multiple imputations were utilized to impute observations with missing values. Results: 179 liver cancer cases were identified. Consumption of freshwater fish and sea fish at least once a week had a strong inverse association with liver cancer risk compared with the lowest intake level, with an adjusted OR of 0.53 (95% CI, 0.38-0.75) and 0.38 (95% CI, 0.19-0.73), respectively. This inverse association was also observed after the imputation. There was no statistically significant association between intake of small fish and liver cancer risk (OR=0.58, 95%, CI 0.32-1.08). Conclusions: Our findings suggest that consumption of freshwater fish and sea fish at least once a week could reduce liver cancer risk.

Keywords: cross-sectional study, fish intake, liver cancer, risk factor

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5826 PNIPAAm-MAA Nanoparticles as Delivery Vehicles for Curcumin Against MCF-7 Breast Cancer Cells

Authors: H. Tayefih, F. farajzade ahari, F. Zarghami, V. Zeighamian, N. Zarghami, Y. Pilehvar-soltanahmadi

Abstract:

Breast cancer is the most frequently occurring cancer among women throughout the world. Natural compounds such as curcumin hold promise to treat a variety of cancers including breast cancer. However, curcumin's therapeutic application is limited, due to its rapid degradation and poor aqueous solubility. On the other hand, previous studies have stated that drug delivery using nanoparticles might improve the therapeutic response to anticancer drugs. Poly (N-isopropylacrylamide-co-methacrylic acid) (PNIPAAm–MAA) is one of the hydrogel copolymers utilized in the drug delivery system for cancer therapy. The aim of this study was to examine the cytotoxic potential of curcumin encapsulated within the NIPAAm-MAA nanoparticle, on the MCF-7 breast cancer cell line. In this work, polymeric nanoparticles were synthesized through the free radical mechanism, and curcumin was encapsulated into NIPAAm-MAA nanoparticles. Then, the cytotoxic effect of curcumin-loaded NIPAAm-MAA on the MCF-7 breast cancer cell line was measured by MTT assays. The evaluation of the results showed that curcumin-loaded NIPAAm-MAA has more cytotoxic effect on the MCF-7 cell line and efficiently inhibited the growth of the breast cancer cell population, compared with free curcumin. In conclusion, this study indicates that curcumin-loaded NIPAAm-MAA suppresses the growth of the MCF-7 cell line. Overall, it is concluded that encapsulating curcumin into the NIPAAm-MAA copolymer could open up new avenues for breast cancer treatment.

Keywords: PNIPAAm-MAA, breast cancer, curcumin, drug delivery

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5825 Sexual Quality of Life in Women with Gynecological Cancer

Authors: Hatice Kahyaoglu Sut, Serap Unsar, Seda Kurt

Abstract:

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

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

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5824 Hypoxia Tolerance, Longevity and Cancer-Resistance in the Mole Rat Spalax – a Liver Transcriptomics Approach

Authors: Hanno Schmidt, Assaf Malik, Anne Bicker, Gesa Poetzsch, Aaron Avivi, Imad Shams, Thomas Hankeln

Abstract:

The blind subterranean mole rat Spalax shows a remarkable tolerance to hypoxia, cancer-resistance and longevity. Unravelling the genomic basis of these adaptations will be important for biomedical applications. RNA-Seq gene expression data were obtained from normoxic and hypoxic Spalax and rat liver tissue. Hypoxic Spalax broadly downregulates genes from major liver function pathways. This energy-saving response is likely a crucial adaptation to low oxygen levels. In contrast, the hypoxiasensitive rat shows massive upregulation of energy metabolism genes. Candidate genes with plausible connections to the mole rat’s phenotype, such as important key genes related to hypoxia-tolerance, DNA damage repair, tumourigenesis and ageing, are substantially higher expressed in Spalax than in rat. Comparative liver transcriptomics highlights the importance of molecular adaptations at the gene regulatory level in Spalax and pinpoints a variety of starting points for subsequent functional studies.

Keywords: cancer, hypoxia, longevity, transcriptomics

Procedia PDF Downloads 132
5823 Immunoliposomes for Co-Delivery of Doxorubicin and Ribonucleotide Reductase M2 Sirna Inhibit of Gastric Cancer Growth

Authors: Jie Gao

Abstract:

The combination of chemotherapy with gene therapy is highly effective in cancer therapy. To achieve combined therapeutic effects in human gastric cancer over expressing EGFR, we developed targeted LPD (liposome-polycation-DNA complex) conjugated with anti-EGFR (epidermal growth factor receptor) Fab’ for co-delivery of doxorubicin (DOX) and ribonucleotide reductase M2 (RRM2) siRNA (DOX-RRM2-TLPD). The results showed that EGFR was over expressed in several gastric cancer cell lines and gastric cancer tissues. Gene Expression Omnibus (GEO) results showed that RRM2 expression was significantly higher in gastric cancer than in non-gastric cancer tissue, and RRM2 siRNA inhibited the proliferation of several gastric cancer cells, indicating that RRM2 is a candidate target for gastric cancer therapy. Confocal studies and flow cytometry showed that DOX-RRM2-TLPD delivered DOX and RRM2 siRNA to EGFR over expressing gastric cancer cells specifically and efficiently both in vitro and in vivo, resulting in enhanced therapeutic effects (cytotoxicity and apoptosis) compared with single-drug loaded or non-targeted controls, including DOX-NC-TLPD (targeted LPD co-delivering DOX and negative control siRNA), RRM2-TLPD (targeted LPD delivering RRM2 siRNA) and DOX-RRM2-NTLPD (non-targeted LPD co-delivering DOX and RRM2 siRNA). The in vivo antitumor assay showed that the average weight of the gastric cancer in mice treated with DOX-RRM2-TLPD was significantly lighter than that of mice treated with other controls. DOX-RRM2-TLPD represents an effective approach for combined therapy of gastric cancer over expressing EGFR.

Keywords: gene therapy, chemotherapy, immunoliposomes, gastric cancer

Procedia PDF Downloads 397
5822 The Effects of Fearing Cancer in Women

Authors: E. Kotrotsiou, A. S. Topsioti, S. Mantzoukas, E. Dragioti, M. Gouva

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Introduction: The literature has demonstrated that individual and psychological factors have a direct effect on the perceptions and attitudes of women with cancer. Objectives: To investigate the relationship between the fear of cancer and anxiety. Aim: To examine the impact of the fear of cancer in women with state and trait anxiety of women. Methods: A community sample of 286 women (mean age 39.6 years, SD = 9.5 ranged 20-60) participated in the current study. The women completed a) State - Trait Anxiety Inventory (STAI) and b) questionnaire concerning socio-demographic information and questions for fear of cancer. Results: The perception of fear in women with cancer is statistically independent from their age (t–test, p = 0.58), their family status (χ2, p = 0.519), their place of residency (χ2, p = 0.148), the manifestation of gynecological cancer (χ2, p = 0.979) or the manifestation of any type of cancer in the family (χ2, p = 0.277). In contrast, it was observed that there was a dependence in relation to a total of phobias (χ2, p = 0.003), the fear of illness (χ2, p< 0.001) and the fear of heights (χ2, p = 0.004). Furthermore, the participants that responded that they feared cancer displayed greater level of stress both as situation (t=-3.462; p=0.001) and as a trait of their personality (t=-4.377; p<0.001), and at the same time they displayed greater levels of depression in comparisons with the other participants. Furthermore, following multiple linear regression analysis it was observed that the participants that responded positively to the question if they feared cancer had 8, 3 units greater stress level as a personality trait in comparison to women that responded negatively to the question if they feared cancer (B=8.3; p=0.016; R2=0.506). Conclusion: Women’s fear of cancer is statistically independent from their age, family status, place of residency, the manifestation of gynaecological cancer and with the manifestation of cancer any type in the family. In contrast, there is a dependency with the total of phobias, fear of illness and fear of heights. Women that state that they have a fear of cancer manifest greater levels of stress from the rest of the participants both as situation and as a trait of their personality (p = 0.001 and p< 0.001 accordingly). In specific, the study demonstrated that the participants that positively to the question if they feared cancer had 8,3 units greater stress level as a personality trait in comparison to women that responded negatively.

Keywords: fear, women health, anxiety, psychology, cancer

Procedia PDF Downloads 237
5821 Theoretical Modelling of Molecular Mechanisms in Stimuli-Responsive Polymers

Authors: Catherine Vasnetsov, Victor Vasnetsov

Abstract:

Context: Thermo-responsive polymers are materials that undergo significant changes in their physical properties in response to temperature changes. These polymers have gained significant attention in research due to their potential applications in various industries and medicine. However, the molecular mechanisms underlying their behavior are not well understood, particularly in relation to cosolvency, which is crucial for practical applications. Research Aim: This study aimed to theoretically investigate the phenomenon of cosolvency in long-chain polymers using the Flory-Huggins statistical-mechanical framework. The main objective was to understand the interactions between the polymer, solvent, and cosolvent under different conditions. Methodology: The research employed a combination of Monte Carlo computer simulations and advanced machine-learning methods. The Flory-Huggins mean field theory was used as the basis for the simulations. Spinodal graphs and ternary plots were utilized to develop an initial computer model for predicting polymer behavior. Molecular dynamic simulations were conducted to mimic real-life polymer systems. Machine learning techniques were incorporated to enhance the accuracy and reliability of the simulations. Findings: The simulations revealed that the addition of very low or very high volumes of cosolvent molecules resulted in smaller radii of gyration for the polymer, indicating poor miscibility. However, intermediate volume fractions of cosolvent led to higher radii of gyration, suggesting improved miscibility. These findings provide a possible microscopic explanation for the cosolvency phenomenon in polymer systems. Theoretical Importance: This research contributes to a better understanding of the behavior of thermo-responsive polymers and the role of cosolvency. The findings provide insights into the molecular mechanisms underlying cosolvency and offer specific predictions for future experimental investigations. The study also presents a more rigorous analysis of the Flory-Huggins free energy theory in the context of polymer systems. Data Collection and Analysis Procedures: The data for this study was collected through Monte Carlo computer simulations and molecular dynamic simulations. The interactions between the polymer, solvent, and cosolvent were analyzed using the Flory-Huggins mean field theory. Machine learning techniques were employed to enhance the accuracy of the simulations. The collected data was then analyzed to determine the impact of cosolvent volume fractions on the radii of gyration of the polymer. Question Addressed: The research addressed the question of how cosolvency affects the behavior of long-chain polymers. Specifically, the study aimed to investigate the interactions between the polymer, solvent, and cosolvent under different volume fractions and understand the resulting changes in the radii of gyration. Conclusion: In conclusion, this study utilized theoretical modeling and computer simulations to investigate the phenomenon of cosolvency in long-chain polymers. The findings suggest that moderate cosolvent volume fractions can lead to improved miscibility, as indicated by higher radii of gyration. These insights contribute to a better understanding of the molecular mechanisms underlying cosolvency in polymer systems and provide predictions for future experimental studies. The research also enhances the theoretical analysis of the Flory-Huggins free energy theory.

Keywords: molecular modelling, flory-huggins, cosolvency, stimuli-responsive polymers

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5820 Mechanisms of Metals Stabilization in the Soil by Biochar Material as Affected by the Low Molecular Weight Organic Acids

Authors: Md. Shoffikul Islam, Hongqing Hu

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Immobilizing trace elements by reducing their mobility and bioavailability through amendment application, especially biochar (BC), is a cost-effective and efficient method to address their toxicity in the soil environment. However, the low molecular weight organic acids (LMWOAs) in the rhizosphere could affect BC's efficiency to immobilize trace metals as the LMWOAs could either mobilize or fix metals in the soils. Therefore, understanding the BC's and LMWOAs' interaction mechanisms on metals stabilization in the rhizosphere is crucial. The present study examined the impact of BC derived from rice husk, tartaric acid (TA), and oxalic acid (OA), and the combination of BC and TA/OA on the changes of cadmium (Cd), lead (Pb), and zinc (Zn) among their geochemical forms through incubation experiment. The changes of zeta potential and X-ray diffraction (XRD) pattern of BC and BC-amended soils to investigate the probable mechanisms of trace elements' immobilization by BC under the attacks of TA and OA were also examined. The rice husk BC at 5% (w/w) was mixed with the air-dry soil (an Anthrosols) contaminated with Cd, Pb, and Zn in the plastic pot. The TA and OA each at 2, 5, 10, and 20 mM kg-1 (w/v) were added separately into the pot. All the ingredients were mixed thoroughly with the soil. A control (CK) treatment was also prepared without BC, TA, and OA addition. After 7, 15, and 60 days of incubation with 60% (w/v) moisture level at 25 °C, the incubated soils were determined for pH and EC and were sequentially extracted to assess the metals' transformation in soil. The electronegative charges and XRD peaks of BC and BC-amended soils were also measured. The BC, low level of TA (2 mM kg-1 soil), and BC plus the low concentration of TA (BC-TA2) addition considerably declined the acid-soluble Cd, Pb, and Zn in which BC-TA2 was found to be the most effective treatment. The trends were reversed concerning the high levels of TA (>5-20 mM kg-1 soil), all levels of OA (2-20 mM kg-1 soil), and the BC plus high levels of TA/OA treatments. BC-TA2 changed the highest amounts of acid-soluble and reducible metals to the oxidizable and residual fractions with time. The most increased electronegative charges of BC-TA2 indicate its (BC-TA2) highest metals' immobilizing efficiency, probably through metals adsorption and fixation with the negative charge sites. The XRD study revealed the presence of P, O, CO32-, and Cl1- in BC, which might be responsible for the precipitation of CdCO3, pyromorphite, and hopeite concerning Cd, Pb, and Zn immobilization, respectively. The findings demonstrated that the low level of TA increased metals immobilization, while the high levels of TA and all levels of OA enhanced their mobilization. The BC-TA2 was the best treatment in stabilizing metals in soil.

Keywords: biochar, immobilization, low molecular weight organic acids, trace elements contaminated soil

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5819 Determination of Prostate Specific Membrane Antigen (PSMA) Based on Combination of Nanocomposite Fe3O4@Ag@JB303 and Magnetically Assisted Surface Enhanced Raman Spectroscopy (MA-SERS)

Authors: Zuzana Chaloupková, Zdeňka Marková, Václav Ranc, Radek Zbořil

Abstract:

Prostate cancer is now one of the most serious oncological diseases in men with an incidence higher than that of all other solid tumors combined. Diagnosis of prostate cancer usually involves detection of related genes or detection of marker proteins, such as PSA. One of the new potential markers is PSMA (prostate specific membrane antigen). PSMA is a unique membrane bound glycoprotein, which is considerably overexpressed on prostate cancer as well as neovasculature of most of the solid tumors. Commonly applied methods for a detection of proteins include techniques based on immunochemical approaches, including ELISA and RIA. Magnetically assisted surface enhanced Raman spectroscopy (MA-SERS) can be considered as an interesting alternative to generally accepted approaches. This work describes a utilization of MA-SERS in a detection of PSMA in human blood. This analytical platform is based on magnetic nanocomposites Fe3O4@Ag, functionalized by a low-molecular selector labeled as JB303. The system allows isolating the marker from the complex sample using application of magnetic force. Detection of PSMA is than performed by SERS effect given by a presence of silver nanoparticles. This system allowed us to analyze PSMA in clinical samples with limits of detection lower than 1 ng/mL.

Keywords: diagnosis, cancer, PSMA, MA-SERS, Ag nanoparticles

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5818 Feasibility of Leukemia Cancer Treatment (K562) by Atmospheric Pressure Plasma Jet

Authors: Mashayekh Amir Shahriar, Akhlaghi Morteza, Rajaee Hajar, Khani Mohammad Reza, Shokri Babak

Abstract:

A new and novel approach in medicine is the use of cold plasma for various applications such as sterilization blood coagulation and cancer cell treatment. In this paper a pin-to-hole plasma jet suitable for biological applications is investigated, characterized and the possibility and feasibility of cancer cell treatment is evaluated. The characterization includes power consumption via Lissajous method, thermal behavior of plasma using Infra-red camera as a novel method, Optical Emission Spectroscopy (OES) to determine the species that are generated. Treatment of leukemia cancer cells is also implemented and MTT assay is used to evaluate viability.

Keywords: Atmospheric Pressure Plasma Jet (APPJ), Plasma Medicine, Cancer cell treatment, leukemia, Optical Emission

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5817 A Review on the Importance of Nursing Approaches in Nutrition of Children with Cancer

Authors: Ş. Çiftcioğlu, E. Efe

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In recent years, cancer has been at the top of diseases that cause death in children. Adequate and balanced nutrition plays an important role in the treatment of cancer. Cancer and cancer treatment is affecting food intake, absorption and metabolism, causing nutritional disorders. Appropriate nutrition is very important for the cancerous child to feel well before, during and after the treatment. There are various difficulties in feeding children with cancer. These are the cancer-related factors. Other factors are environmental and behavioral. As health professionals who spend more time with children in the hospital, nurses should be able to support the children on nutrition and help them to have balanced nutrition. This study aimed to evaluate the importance of nursing approaches in the nutrition of children with cancer. This article is planned as a review article by searching the literature on this field. Anorexia may develop due to psychogenic causes or chemotherapeutic agents or accompanying infections and nutrient uptake may be reduced.  In addition, stomatitis, mucositis, taste and odor changes in the mouth, the feeling of nausea, vomiting and diarrhea can also reduce oral intake and result in significant losses in the energy deficit. In assessing the nutritional status of children with cancer, determining weight loss and good nutrition is essential anamnesis of a child.  Some anthropometric measurements and biochemical tests should be used to evaluate the nutrition of the child. The nutritional status of pediatric cancer patients has been studied for a long time and malnutrition, in particular under nutrition, in this population has long been recognized. Yet, its management remains variable with many malnourished children going unrecognized and consequently untreated. Nutritional support is important to pediatric cancer patients and should be integrated into the overall treatment of these children.

Keywords: cancer treatment, children, complication, nutrition, nursing approaches

Procedia PDF Downloads 192