Search results for: pediatric cancer

Authors: Radoslav Stojchevski, Leonid Poretsky, Dimiter Avtanski

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Proinflammatory cytokines play an important role in cancer initiation and progression by mediating the intracellular communication between the cancer cells and tumor microenvironment. Increased tumor growth causing reduced oxygen concentration and oxygen pressure commonly result in hypoxia. Mechanistically, hypoxia is characterized by stabilization and nuclear translocation of hypoxia-inducible factor 1 alpha (HIF-1α) followed by propagation of molecular pathway cascade involving multiple downstream targets. Cobalt(II) chloride (CoCl₂) is commonly used to mimic hypoxia in experimental conditions since it directly induces the expression of HIF-1α. The aim of the present study was to investigate the in vitro effects and the molecular mechanisms by which hypoxia regulates the cytokine secretory profile of breast cancer cells. As a model for this study, we used several breast cancer cell lines bearing various molecular characteristics and metastatic potential (MDA-MB-231 (clauding low, ER-/PR-/HER²⁻), MCF-7 (luminal A, ER⁺/PR⁺/HER²⁻), and BT-474 (liminal B, ER⁺/PR⁺/HER²⁺)). We demonstrated that breast cancer cells secrete numerous cytokines and cytokine ligands, including interleukins, chemokines, and growth factors. Treatment with CoCl₂significantly modulated the breast cancer cells' cytokine expression in a concentration- and time-dependent manner. These effects were mediated via activation of several signaling pathways (JNK/SAPK1, NF-κB, STAT5A/B, and Erk/MAPK1/2). Taken together, the present data define some of the molecular mechanisms by which hypoxia affects the breast cancer cells' cytokine secretory profile, thus contributing to the development of novel therapies for metastatic breast cancer.

Keywords: breast cancer, cytokines, cobalt(II) chloride (CoCl₂), hypoxia

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Authors: Sana Gul, Sheeba Murad, Aneela Javed

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Introduction: Human Papilloma Virus (HPV) is small DNA virus mostly infecting mucosa and cutaneous keratinocytes. So far, more than 200 Human papillomaviruses are known. HPV have been divided into high- and low-risk on the basis of their oncogenic potential. High risk HPV is considered to be the main etiological cause for cervical cancer. Objective: Current study was designed to screen the local cervical cancer patients from the twin cities of Pakistan for the occurance of high risk HPV. Methodology: A total of 67 formalin fixed paraffin-embedded samples of cervical cancer biopsies were obtained from the government hospitals in Islamabad and Rawalpindi. Cervical cancer biopsies were examined for the presence of HPV DNA. Polymerase chain reaction (PCR) was used for the amplification of a region in the HPV-L1 gene for the general detection of the Papilloma virus and for the genotype specific detection of high risk HPV 16 and 18 using the GP5/GP6 primers and genotype specific primers respectively. Results: HPV DNA was detected in 59 out of 67 samples analyzed. 30 samples showed the presence of HPV16 while 22 samples were positive for HPV 18 . HPV subtype could not be determined in 7 samples. Conclusion: Our results show a strong association between HPV infection and cervical cancer among women in twin cities of Pakistan. One way to minimize the disease burden in relation to HPV infection in Pakistani population is the use of prophylactic vaccines and routine screening. An early diagnosis of HPV infection will allow better health management to reduce the risk of developing cervical cancer.

Keywords: cervical cancer, Pakistan, human papillomavirus, HPV 16

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Authors: Ian Campbell, Gillian Mitchell, Paul James, Na Li, Ella Thompson

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The genetic cause of the majority of multiple-case breast cancer families remains unresolved. Next generation sequencing has emerged as an efficient strategy for identifying predisposing mutations in individuals with inherited cancer. We are conducting whole exome sequence analysis of germ line DNA from multiple affected relatives from breast cancer families, with the aim of identifying rare protein truncating and non-synonymous variants that are likely to include novel cancer predisposing mutations. Data from more than 200 exomes show that on average each individual carries 30-50 protein truncating mutations and 300-400 rare non-synonymous variants. Heterogeneity among our exome data strongly suggest that numerous moderate penetrance genes remain to be discovered, with each gene individually accounting for only a small fraction of families (~0.5%). This scenario marks validation of candidate breast cancer predisposing genes in large case-control studies as the rate-limiting step in resolving the missing heritability of breast cancer. The aim of this study is to screen genes that are recurrently mutated among our exome data in a larger cohort of cases and controls to assess the prevalence of inactivating mutations that may be associated with breast cancer risk. We are using the Agilent HaloPlex Target Enrichment System to screen the coding regions of 168 genes in 1,000 BRCA1/2 mutation-negative familial breast cancer cases and 1,000 cancer-naive controls. To date, our interim analysis has identified 21 genes which carry an excess of truncating mutations in multiple breast cancer families versus controls. Established breast cancer susceptibility gene PALB2 is the most frequently mutated gene (13/998 cases versus 0/1009 controls), but other interesting candidates include NPSR1, GSN, POLD2, and TOX3. These and other genes are being validated in a second cohort of 1,000 cases and controls. Our experience demonstrates that beyond PALB2, the prevalence of mutations in the remaining breast cancer predisposition genes is likely to be very low making definitive validation exceptionally challenging.

Keywords: predisposition, familial, exome sequencing, breast cancer

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Authors: Aruha Khan, Brynn E. Kankel, Paraskevi Papadopoulou

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In recent years, extensive research upon ‘stress’ has provided insight into its two distinct guises, namely the short–term (fight–or–flight) response versus the long–term (chronic) response. Specifically, the long–term or chronic response is associated with the suppression or dysregulation of immune function. It is also widely noted that the occurrence of cancer is greatly correlated to the suppression of the immune system. It is thus necessary to explore the impact of long–term or chronic stress upon the prevalence and risk of cancer. To what extent can the dysregulation of immune function caused by long–term exposure to stress be controlled or minimized? This study focuses explicitly upon immunosuppression due to its ability to increase disease susceptibility, including cancer itself. Based upon an analysis of the literature relating to the fundamental structure of the immune system alongside the prospective linkage of chronic stress and the development of cancer, immunosuppression may not necessarily correlate directly to the acquisition of cancer—although it remains a contributing factor. A cross-sectional analysis of the survey data from the University of Tennessee Medical Center (UTMC) and Harvard Medical School (HMS) will provide additional supporting evidence (or otherwise) for the hypothesis of the study about whether immunosuppression (caused by the chronic stress response) notably impacts the prevalence of cancer. Finally, a multidimensional framework related to education on chronic stress and its effects is proposed.

Keywords: immune system, immunosuppression, long–term (chronic) stress, risk of cancer

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Authors: Mitra JahangirRad, Sheida Sodagar, Maryam Bahrami Hidaji

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This study was conducted with the aim of comparing anxiety, stress, depression and attitude towards death among patients with breast cancer who have undergone mastectomy or breast-conserving surgery. The study method is causal-comparative. Statistical population was all patients with breast cancer referring to Medical Center of Panjom Azar Hospital in Gorgan or oncologists' offices in this city within eight months. They were selected using purposive sampling. Sample size of this study was 45 patients with breast cancer undergoing mastectomy and 70 patients under breast-conserving surgery. Measurement tools in this study were depression, anxiety, and stress scale (Dass-21) as well as Death Attitude Profile-Revised (DAPR). Results of this study in hypotheses investigation showed that anxiety, stress and depression among patients with breast cancer, undergoing mastectomy or breast-conserving surgery is significantly different. However, their attitudes towards death do not differ. From these findings, it can be concluded that although most patients with breast cancer encounter many psychological problems, patients undergoing mastectomy experience more anxiety, stress and depression relative to patients with breast-conserving surgery and it seems that they need more supportive therapy.

Keywords: anxiety, breast cancer, depression, death, mastectomy

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Authors: I. Ramalho, S. Campos, M. Dias

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Introduction: Endometriosis may play a role in the pathogenesis of ovarian cancer (OC), however, the risk and prognosis have not been well established. The association between these two pathologies could have an important impact on prevention and early diagnosis of OC. Objective: To analyze the prevalence of endometriosis associated ovarian cancer and related clinical, epidemiological and histopathological issues. Design: We conducted a retrospective case series analysis of patients diagnosed with endometriosis and ovarian cancer in the Gynecology Department of Coimbra University Hospital Center since 2006 to 2015. Methods: We collected data from women diagnosed with ovarian cancer, with anatomopathology records reporting findings of endometriosis in ovarian cancer patients. Patients were retrieved from the pathological records and appropriate medical records were retrospectively reviewed. Statistical analysis was performed using SPSS 22.0. Results: Histological evidence of endometriosis was found in 17 out of 261 patients diagnosed with ovarian cancer (OC) (6.51%). The most usual symptoms were pelvic pain, abdominal distension, asthenia, ascites, weight loss and nausea. Mean age at diagnosis was 61.2 ± 15.1, 41-86 years old, 33.3% were pre-menopausal patients and cancer stage distribution was predominantly stage I (31.3%) and stage III (56.3%). OC occurred unilaterally in 14 patients and 2 patients were diagnosed with a synchronous ovarian and endometrial cancer. Regarding histological type, 10 OC were classified as clear cell carcinoma (CCC), 4 endometrioid carcinomas (EC) and 3 mixed type (clear cell and endometrioid). Four ovarian carcinomas presumably arose from endometriomas: 3 CCC and 1 EC. Conclusions: In accordance with previous studies, clear cell was the most common pathological type in endometriotic patients, followed by endometrioid carcinomas, and two rare synchronous ovarian and endometrial carcinomas were registered. Although endometriosis association to OC is uncommon, endometriosis should be managed with special care in order to early diagnosis.

Keywords: endometriosis, histology, observational study, ovarian cancer

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Authors: Jun Hong Lee

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Background: Alzheimer`s disease (AD) I: creases with age and is characterized by the premature progressive loss of neuronal cell. In contrast, cancer cells have inappropriate cell proliferation and resistance to cell death. Objective: We evaluated the association between cancer and AD and also examined the specific types of cancer. Patients and Methods/Material and Methods: This retrospective, nationwide, longitudinal study used National Health Insurance Service – Senior cohort (NHIS-Senior) 2002-2013, which was released by the KNHIS in 2016, comprising 550,000 random subjects who were selected from over than 60. The study included a cohort of 4,408 patients who were first diagnoses as AD between 2003 and 2005. To match each dementia patient, 19,150 subjects were selected from the database by Propensity Score Matching. Results: We enrolled 4,790 patients for analysis in this cohort and the prevalence of AD was higher in female (19.29%) than in male (17.71%). A higher prevalence of AD was observed in the 70-84 year age group and in the higher income status group. A total of 540 cancers occurred within the observation interval. Overall cancer was less frequent in those with AD (12.25%) than in the control (18.46%), with HR 0.704 (95% Confidence Intervals (CIs)=0.0.64-0.775, p-Value < 0.0001). Conclusion: Our data showed a decreased incidence of overall cancers in patients with AD similar to previous studies. Patients with AD had a significantly decreased risk of colon & rectum, lung and stomach cancer. This finding lower than but consistent with Western countries. We need further investigation of genetic evidence linking AD to cancer.

Keywords: Alzheimer, cancer, nationwide, longitudinal study

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Authors: Ossama Abdelmotaal, Olfat Shaker, Tarek Salman, Lamiaa Nabeel, Mostafa Shabayek

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Colorectal Cancer (CRC) is an important worldwide health problem. Colonoscopy is used in detecting CRC suffer from drawbacks where colonoscopy is an invasive method. This study validates easier and less time-consuming techniques to evaluate the usefulness of detecting miRNA-21, miRNA-215 and miRNA-378 in the sera of colorectal cancer patients as new diagnostic tools. This study includes malignant (Colo Rectal Cancer patients, n= 64)) and healthy (n=27) groups. The studied groups were subjected to colonoscopic examination and estimation of miRNA-21, miRNA-215 and miRNA-378 in sera by RT-PCR. miRNA-21 showed the statistically significantly highest median fold change. miRNA-378 showed statistically significantly lower value (Both showed over-expression). miRNA-215 showed the statistically significantly lowest median fold change (It showed down-regulation). Overall the miRNA (21-215 and 378) appear to be promising method of detecting CRC and evaluating its stages.

Keywords: colorectal cancer, miRNA-21, miRNA-215, miRNA-378

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Authors: Diwei Lin, Amanda Jh. Tan

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We present a very rare case of de novo large cell neuroendocrine carcinoma of the prostate (LCNEC) in an 84-year-old male on a background of high-grade, muscle-invasive transitional cell carcinoma of the bladder. While NE tumours account for 1% to 5% of all cases of prostate cancer and scattered NE cells can be found in 10% to 100% of prostate adenocarcinomas, pure LCNEC of the prostate is extremely rare. Most LCNEC of the prostate is thought to originate by clonal progression under the selection pressure of therapy and refractory to long-term hormonal treatment for adenocarcinoma of the prostate. De novo LCNEC is only described in case reports and is thought to develop via direct malignant transformation. Limited data in the English literature makes it difficult to accurately predict the prognosis of LCNEC of the prostate. However, current evidence suggesting that increasing NE differentiation in prostate adenocarcinoma is associated with a higher stage, high-grade disease, and a worse prognosis.

Keywords: large cell neuroendocrine cancer, prostate cancer, refractory cancer, medical and health sciences

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Authors: Wilfred Elliam

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Background: Pain is a prevalent and debilitating symptom among breast cancer patients, impacting their quality of life and overall well-being. The experience of pain in this population is multifaceted, influenced by a combination of disease-related factors, treatment side effects, and individual characteristics. Despite advancements in cancer treatment and pain management, many breast cancer patients continue to suffer from chronic pain, which can persist long after the completion of treatment. Understanding the progression of pain in breast cancer patients over time and identifying its correlates is crucial for effective pain management and supportive care strategies. The purpose of this research is to understand the patterns and progression of pain experienced by breast cancer survivors over time. Methods: Data were collected from breast cancer patients at Hartford Hospital at four time points: baseline, 3, 6 and 12 weeks. Key variables measured include pain, body mass index (BMI), fatigue, musculoskeletal pain, sleep disturbance, and demographic variables (age, employment status, cancer stage, and ethnicity). Binomial generalized linear mixed models were used to examine changes in pain and symptoms over time. Results: A total of 100 breast cancer patients aged  18 years old were included in the analysis. We found that the effect of time on pain (p = 0.024), musculoskeletal pain (p= <0.001), fatigue (p= <0.001), and sleep disturbance (p-value = 0.013) were statistically significant with pain progression in breast cancer patients. Patients using aromatase inhibitors have worse fatigue (<0.05) and musculoskeletal pain (<0.001) compared to patients with Tamoxifen. Patients who are obese (<0.001) and overweight (<0.001) are more likely to report pain compared to patients with normal weight. Conclusion: This study revealed the complex interplay between various factors such as time, pain, sleep disturbance in breast cancer patient. Specifically, pain, musculoskeletal pain, sleep disturbance, fatigue exhibited significant changes across the measured time points, indicating a dynamic pain progression in these patients. The findings provide a foundation for future research and targeted interventions aimed at improving pain in breast cancer patient outcomes.

Keywords: breast cancer, chronic pain, pain management, quality of life

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Authors: Mary Bernardin, Margie Batek, Joseph Moen, David Schnadower

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Background: Exposure to violence not only has negative psychological impact on children but is a risk factor for children becoming recurrent victims of violence. However, little is known regarding the degree to which child victims of violence are exposed to trauma at home and in their community, or its association with specific psychological diagnoses. Objective: The aims of this study were to perform in-depth characterizations of family, community and psychological wellness amongst pediatric victims of interpersonal violence. Methods: As standard of care at the Saint Louis Children’s Hospital pediatric emergency department (ED), social workers perform in-depth interviews with all children presenting due to violent interpersonal encounters. In this retrospective cross-sectional study, we collected data from social work interviews on family structure, exposure to violence in the community and the home, as well as history of psychological diagnoses amongst children ages 8-19 years who presented to the ED for injuries related to interpersonal violence from 2014-2017. Results: A total of 407 patients presenting to the ED for an interpersonal violent encounter were analyzed. The average age of studied youths was 14.7 years (SD 2.5). Youths were 97.5% African American ethnicity and 66.6% male. 67.8% described their home having a nonnuclear family structure, 50% of which reported living with a single mother. Of the 21% who reported having incarcerated family members, 56.3% reported their father being incarcerated, 15% reported their mother being incarcerated, and 12.5% reported multiple family members being incarcerated. 11.3% reported witnessing domestic violence in their home. 12.8% of youths reported some form of child abuse. The type of child abuse was not specified in 29.3% of cases, but physical abuse (32.8%) followed by sexual abuse (22.4%) were the most commonly reported. 14.5% had history of placement in foster care and/or adoption. 64% reported having witnessed violence in their community. 30.2% reported having lost friends or family due to violence, and of those, 26.4% reported the loss of a cousin, 18.9% the loss of a friend, 16% the loss of their father, and 12.3% the loss of their brother due to violence. Of the 22.4% youths with psychiatric diagnose(s), 48.4% had multiple diagnoses, the most common of which were ADD/ADHD (62.6%), followed by depression (31.9%), bipolar disorder (27.5%) and anxiety (15.4%). Conclusions: A remarkable proportion of children presenting to EDs due to interpersonal violence have a history of exposure to instability and violence in their homes and communities. Additionally, psychological diagnoses are frequent among pediatric victims of violence. More research is needed to better understand the association between trauma exposure, psychological health and violent victimization amongst children.

Keywords: community violence, emergency department, pediatric interpersonal violence, pediatric trauma, psychological effects of trauma

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Authors: Oluwaponmile D. Alao

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In this paper, two models have been developed to ascertain the best network needed for diagnosis of breast cancer. Breast cancer has been a disease that required the attention of the medical practitioner. Experience has shown that misdiagnose of the disease has been a major challenge in the medical field. Therefore, designing a system with adequate performance for will help in making diagnosis of the disease faster and accurate. In this paper, two models: backpropagation neural network and support vector machine has been developed. The performance obtained is also compared with other previously obtained algorithms to ascertain the best algorithms.

Keywords: breast cancer, data mining, neural network, support vector machine

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Authors: Zakaria Baka, Halima Alem

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Cancer is a major worldwide health problem that has caused around ten million deaths in 2020. In addition, efforts to develop new anti-cancer drugs still face a high failure rate. This is partly due to the lack of preclinical models that recapitulate in-vivo drug responses. Indeed conventional cell culture approach (known as 2D cell culture) is far from reproducing the complex, dynamic and three-dimensional environment of tumors. To set up more in-vivo-like cancer models, 3D bioprinting seems to be a promising technology due to its ability to achieve 3D scaffolds containing different cell types with controlled distribution and precise architecture. Moreover, the introduction of microfluidic technology makes it possible to simulate in-vivo dynamic conditions through the so-called “cancer-on-chip” platforms. Whereas several cancer types have been modeled through the cancer-on-chip approach, such as lung cancer and breast cancer, only a few works describing ovarian cancer models have been described. The aim of this work is to combine 3D bioprinting and microfluidic technics with setting up a 3D dynamic model of ovarian cancer. In the first phase, alginate-gelatin hydrogel containing SKOV3 cells was used to achieve tumor-like structures through an extrusion-based bioprinter. The desired form of the tumor-like mass was first designed on 3D CAD software. The hydrogel composition was then optimized for ensuring good and reproducible printability. Cell viability in the bioprinted structures was assessed using Live/Dead assay and WST1 assay. In the second phase, these bioprinted structures will be included in a microfluidic device that allows simultaneous testing of different drug concentrations. This microfluidic dispositive was first designed through computational fluid dynamics (CFD) simulations for fixing its precise dimensions. It was then be manufactured through a molding method based on a 3D printed template. To confirm the results of CFD simulations, doxorubicin (DOX) solutions were perfused through the dispositive and DOX concentration in each culture chamber was determined. Once completely characterized, this model will be used to assess the efficacy of anti-cancer nanoparticles developed in the Jean Lamour institute.

Keywords: 3D bioprinting, ovarian cancer, cancer-on-chip models, microfluidic techniques

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Authors: Firas Gerges, Frank Y. Shih

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Malignant melanoma, known simply as melanoma, is a type of skin cancer that appears as a mole on the skin. It is critical to detect this cancer at an early stage because it can spread across the body and may lead to the patient's death. When detected early, melanoma is curable. In this paper, we propose a deep learning model (convolutional neural networks) in order to automatically classify skin lesion images as malignant or benign. Images underwent certain pre-processing steps to diminish the effect of the normal skin region on the model. The result of the proposed model showed a significant improvement over previous work, achieving an accuracy of 97%.

Keywords: deep learning, skin cancer, image processing, melanoma

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Authors: Vidhula Ahire, Amit Kumar, K. P. Mishra, Gauri Kulkarni

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Herbal polyphenols have gained significance because of their increasing promise in prevention and treatment of cancer. Therefore, development of a dietary compound as an effective radiosensitizer and a radioprotector is highly warranted for cervical cancer patients undergoing therapy. This study describes the cytotoxic effects of the flavonoid, ellagic acid (EA) when administered either alone or in combination with gamma radiation on cervical cancer HeLa cells in vitro. Apoptotic index and proliferation were measured by using trypan blue assay. Reproductive cell death was analyzed by clonogenic assay. Propidium iodide staining for flowcytometry was performed to analyze cell cycle modulation. Nuclear and mitochondrial changes were studied with specific dyes. DNA repair kinetics was analyzed by immunofluorescence assay. Evaluation and comparison of EA effects were performed with other clinically used breast cancer drugs. When tumor cells were exposed to 2 and 4 Gy of irradiation in presence of EA (10 μM), it yielded a synergistic cytotoxic effect on cervical cancer cells whereas in NIH3T3 cells it reversed the injury caused by irradiation and abetted in the regaining of normal healthy cells. At 24h ~25foci/cell was observed and 2.6 fold decrease in the mitochondrial membrane potential. Up to 40% cell were arrested in the G1 phase and 20-36% cells exhibited apoptosis. Our results demonstrate the role of increased apoptosis and cell cycle modulation in the mechanism of EA mediated radiosensitization of cervical cancer cells and thus advocating EA as an adjuvant for preclinical trials in cancer chemo- radiotherapy.

Keywords: cervical cancer, ellagic acid, sensitization, radiation therapy

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Authors: Jiwan Kumar, Pooja, Sandeep Negi, Anjum Rouf, Amit Kumar, Naveen Lakra

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In modern times where, health issues are increasing day by day, breast cancer is also one of them, which is very crucial and really important to find in the early stages. Doctors can use this model in order to tell their patients whether a cancer is not harmful (benign) or harmful (malignant). We have used the knowledge of machine learning in order to produce the model. we have used algorithms like Logistic Regression, Random forest, support Vector Classifier, Bayesian Network and Radial Basis Function. We tried to use the data of crucial parts and show them the results in pictures in order to make it easier for doctors. By doing this, we're making ML better at finding breast cancer, which can lead to saving more lives and better health care.

Keywords: Bayesian network, radial basis function, ensemble learning, understandable, data making better, random forest, logistic regression, breast cancer

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Authors: Lamis Naddaf, Yuval Tabach

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We identified missense genetic variants with the potential to enhance resistance against cancer. Such a field has not been widely explored as researchers tend to investigate the mutations that cause diseases, in response to the suffering of patients, rather than those mutations that protect from them. In conjunction with the genomic revolution and the advances in genetic engineering and synthetic biology, identifying the protective variants will increase the power of genotype-phenotype predictions and have significant implications for improved risk estimation, diagnostics, prognosis, and even personalized therapy and drug discovery. To approach our goal, we systematically investigated the sites of the coding genomes and selected the alleles that showed a correlation with the species’ cancer resistance. Interestingly, we found several amino acids that are more generally preferred (like the Proline) or avoided (like the Cysteine) by the resistant species. Furthermore, Cancer resistance in mammals and reptiles is significantly predicted by the number of the predicted protecting variants (PVs) a species has. Moreover, PVs-enriched-genes are enriched in pathways relevant to tumor suppression. For example, they are enriched in the Hedgehog signaling and silencing pathways, which its improper activation is associated with the most common form of cancer malignancy. We also showed that the PVs are mostly more abundant in healthy people compared to cancer patients within different human races.

Keywords: cancer resistance, protecting variant, naked mole rat, comparative genomics

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Authors: Fatemeh Zeinali Sehrig

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Background: miRNAs play an important role in the post-transcriptional regulation of genes, including genes involved in DNA methylation (DNMTs), and are also important regulators of oncogenic pathways. The study of microRNAs and DNMTs in breast cancer allows the development of targeted treatments and early detection of this cancer. Methods and Materials: Clinical Patients and Samples: Institutional guidelines, including ethical approval and informed consent, were followed by the Ethics Committee (Ethics code: IR.IAU.TABRIZ.REC.1401.063) of Tabriz Azad University, Tabriz, Iran. In this study, tissues of 100 patients with breast cancer and tissues of 100 healthy women were collected from Noor Nejat Hospital in Tabriz. The basic characteristics of the patients with breast cancer included: 1)Tumor grade(Grade 3 = 5%, Grade 2 = 87.5%, Grade 1 = 7.5%), 2)Lymph node(Yes = 87.5%, No = 12.5%), 3)Family cancer history(Yes = 47.5%, No = 41.3%, Unknown = 11.2%), 4) Abortion history(Yes = 36.2%).In silico methods (data gathering, process, and build networks): Gene Expression Omnibus (GEO), a high-throughput genomic database, was queried for miRNAs expression profiles in breast cancer. For Experimental protocol Tissue Processing, Total RNA isolation, complementary DNA(cDNA) synthesis, and quantitative real time PCR (QRT-PCR) analysis were performed. Results: In the present study, we found significant (p.value<0.05) changes in the expression level of miRNAs and DNMTs in patients with breast cancer. In bioinformatics studies, the GEO microarray data set, similar to qPCR results, showed a decreased expression of miRNAs and increased expression of DNMTs in breast cancer. Conclusion: According to the results of the present study, which showed a decrease in the expression of miRNAs and DNMTs in breast cancer, it can be said that these genes can be used as important diagnostic and therapeutic biomarkers in breast cancer.

Keywords: gene expression omnibus, microarray dataset, breast cancer, miRNA, DNMT (DNA methyltransferases)

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Authors: Sajjad Jafari, Reza Akbari

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Background and Aim: Chrysin, a flavonoid compound found in medicinal plants, honey, and propolis, has potential biological activities that make it an important perspective in the treatment of infectious and cancer diseases. The aim of this review study is to evaluate the biological activities of chrysin in the treatment of infectious and cancer diseases. Material and Methods: The present study is a review study that searched reputable scientific databases such as PubMed, Google Scholar, Scopus, and Web of Science from 2000 to 2023 using keywords such as antimicrobial, antifungal, chrysin, anticancer, antioxidants, and infectious diseases. The researchers examined 25 articles to determine the biological activities of chrysin. Results: Chrysin has high inhibitory or lethal activities on gram-positive and gram-negative bacteria, including Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis, and Enterococcus faeces. It also has anti-biofilm effects and antifungal effects on strains such as Aspergillus niger and Candida albicans. Chrysin also has anticancer effects on various cancers, including colorectal cancer, pancreatic cancer, breast cancer, and MCF-7 cancer, which have been confirmed in vitro and in vivo. Conclusion: Chrysin has the potential as an important therapeutic option in the treatment of infectious and cancer diseases. Its high antimicrobial and anticancer activities, combined with its low toxicity in nanoparticle form, make it a promising candidate for further clinical trials. The production of anti-microbial and anti-cancer drugs from natural substances, such as chrysin, is a valuable contribution to the field of medicine.

Keywords: chrysin, antimicrobial, anticancer, infectious diseases

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Authors: Memnun Seven, Mine Bahar, Aygül Akyüz, Hatice Erdoğan

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Background: The workplace has been deemed a suitable location for educating many women at once about cancer screening. Objective: To determine how group education about early diagnostic methods for breast and cervical cancer affects women’s behavior and readiness to receive mammography and Pap smears. Methods: This semi-interventional study was conducted at a textile factory in Istanbul, Turkey. Female workers (n = 125) were included in the study. A participant identification form and knowledge evaluation form developed for this study, along with the trans-theoretical model, were used to collect data. A 45-min interactive group education was given to the participants. Results: Upon contacting participants 3 months after group education, 15.4% (n = 11) stated that they had since received a mammogram and 9.8% (n = 7) a Pap smear. As suggested by the trans-theoretical model, group education increased participants’ readiness to receive cancer screening, along with their knowledge of breast and cervical cancer. Conclusions: Group education positively impacted women’s knowledge of cancer and their readiness to receive mammography and Pap smears. Group education can therefore potentially create awareness of cancer screening tests among women and improve their readiness to receive such tests.

Keywords: cancer screening, educational intervention, participation, women

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Authors: C. Panebianco, K. Adamberg, S. Adamberg, C. Saracino, M. Jaagura, K. Kolk, A. Di Chio, P. Graziano, R. Vilu, V. Pazienza

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Background/Aims: Despite recent advances in treatment options, a modest impact on the outcome of the pancreatic cancer (PC) is observed so far. Short-term fasting cycles have the potential to improve the efficacy of chemotherapy against PC. However, diseased people may refuse to follow the fasting regimen and fasting may worsen the weight loss often occurring in cancer patients. Therefore, alternative approaches are needed. The aim of this study was to assess the effect of Engineered Low glycemic food ELGIF mimicking diet on growth of cancer cell lines in vitro and in an in vivo pancreatic cancer mouse xenograft model. Materials and Methods: BxPC-3, MiaPaca-2 and Panc-1 cells were cultured in control and ELGIF mimicking diet culturing condition to evaluate the tumor growth and proliferation pathways. Pancreatic cancer xenograft mice were subjected to ELGIF to assess the tumor volume and weight as compared to mice fed with control diet. Results: Pancreatic cancer cells cultured in ELGIF mimicking medium showed decreased levels of proliferation as compared to those cultured in the standard medium. Consistently, xenograft pancreatic cancer mice subjected to ELGIF diet displayed a significant decrease in tumor growth. Conclusion: A positive effect of ELGIF diet on proliferation in vitro is associated with the decrease of tumor progression in the in vivo PC xenograft mouse model. These results suggest that engineered dietary interventions could be supportive as synergistic approach to enhance the efficacy of existing cancer treatments in pancreatic cancer patients.

Keywords: functional food, microbiota, mouse model, pancreatic cancer

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Authors: Valerie A. Conrade

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Introduction: A large body of literature suggests patients who complete fecal immunochemical testing (FIT) kits are likely to identify colorectal cancer sooner than those who do not complete FIT kits. Background: Patients who do not participate in preventative measures such as the FIT kit are at a higher risk of colorectal cancer growing unnoticed. The objective was to see if the method the principal investigator (PI) uses to educate clinical staff on the importance of FIT kit administration provides an increased amount of FIT kit dissemination to patients post clinical education. Methodologies: Data collection via manual tallies took place before and after the clinical staff was educated on the importance of FIT kits. Results: The results showed an increase in FIT kit dissemination post clinical staff education. Through enhanced instruction to the clinical staff regarding the importance of FIT kits, expanding their knowledge on preventative measures to detect colorectal cancer positively impacted nurses and, in turn, their patients.

Keywords: colon cancer, education, fecal immunochemical testing, nursing

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Authors: Arindam Pramanik, Parimal Karmakar

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We have explored the synergistic anti-cancer activity of copper ion and acetylacetone complex containing 1,3 diketone group (like curcumin) in metallorganic compound “Copper acetylacetonate” (CuAA). The cytotoxicity mechanism of CuAA complex was evaluated on various cancer cell lines in vitro. Among these, reactive oxygen species (ROS), glutathione level (GSH) in the cell was found to increase. Further mitochondrial membrane damage was observed. The fate of cell death was found to be induced by apoptosis. For application purpose, we have developed a novel biodegradable, non-toxic polymer-based nanoparticle which has hydrophobically modified core for loading of the CuAA. Folic acid is conjugated on the surface of the polymer (chitosan) nanoparticle for targeting to cancer cells for minimizing toxicity to normal cells in-vivo. Thus, this novel drug CuAA has an efficient anticancer activity which has been targeted specifically to cancer cells through polymer nanoparticle.

Keywords: anticancer, apoptosis, copper nanoparticle, targeted drug delivery

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Authors: Christopher G. Harris, Guy D. Eslick

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Purpose: Lobular carcinoma in situ (LCIS) is a known risk factor for breast cancer of unclear significance when detected in association with invasive carcinoma. This meta-analysis aims to determine the impact of LCIS on local recurrence risk for individuals with breast cancer treated with breast conservation therapy to help guide appropriate treatment strategies. Methods: We identified relevant studies from five electronic databases. Studies were deemed suitable for inclusion where they compared patients with invasive breast cancer and concurrent LCIS to those with breast cancer alone, all patients underwent breast conservation therapy (lumpectomy with adjuvant radiation therapy), and local recurrence was evaluated. Recurrence data were pooled by use of a random effects model. Results: From 1488 citations screened by our search, 8 studies were deemed suitable for inclusion. These studies comprised of 908 cases and 10638 controls. Median follow-up time was 90 months. There was a significantly increased overall risk of local breast cancer recurrence for individuals with LCIS in association with breast cancer following breast conservation therapy [pOR 1.87; 95% CI 1.14-3.04; p = 0.012]. The risk of local recurrence was non-significantly increased at 5 [pOR 1.09; 95% CI 0.48-2.48; p = 0.828] and 10 years [pOR 1.90; 95% CI 0.89-4.06; p = 0.096]. Conclusions: Individuals with LCIS in association with invasive breast cancer have an increased risk of local recurrence following breast conservation therapy. This supports consideration of aggressive local control of LCIS by way of completion mastectomy or re-excision for certain high-risk patients.

Keywords: breast cancer, breast conservation therapy, lobular carcinoma in situ, lobular neoplasia, local recurrence, meta-analysis

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Authors: Alireza Barari, Maryam Firoozi, Maryam Ebrahimzadeh, Romina Roohan Ardeshiri, Maryam Kamarloeei

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Background: The The purpose of this study was to evaluate the effect of six-week aerobic training and taxol consumption on interleukin 8 and Plasminogen Activator Inhibitor-1 (PAI-1) in mice with cervical cancer. Material and method: In this experimental study, 40 female C57 mice, eight weeks old, were randomly divided into 4 groups: cancer, cancer-taxol complement, cancer-training and cancer-training - taxol complement with 10 mice in each group. The implantation of cancerous tumors was performed under the skin of the upper pelvis. The training group completed the endurance training protocol, which included 3 sessions per week, 50 minutes per session, at a speed of 14-18 m/s for six weeks. A dose of 60 mg/ kg/day, a pure extract of Taxol was injected peritoneal Data were analyzed by t-test, One-way ANOVA and post hoc Bonferron's at the significant level P<0. 05. Results: The results showed that there was a significant difference between mean values of interleukin-8 (P < 0.05, F = 12.25) and the plasminogen activator inhibitor-1 (P < 0.05, P=0.10737) in four groups. A significance level of less than 0.05 in Tukey test for both variables also showed a significant difference between the "control" group and the complementary "exercise" group. Namely, six weeks of aerobic training, along with taxol, have a significant effect on the level of plasminogen activator inhibitor-1 and interleukin-8 mice with cervical cancer. Conclusion: Considering the effect of training on these variables, this type of exercise can be used as a complementary therapeutic approach along with other therapies for cervical cancer.

Keywords: cervical cancer, taxol, endurance training, interleukin 8, plasminogen activator inhibitor-1

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Authors: Dalma Dojcsák, Csaba Váradi, Flóra Farkas, Tamás Farkas, János Papp, Béla Viskolcz

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Background: Appendicitis is a common acute inflammatory condition in both children and adults, but current laboratory markers such as C-reactive protein (CRP), white blood cell count (WBC), absolute neutrophil count (ANC), and red blood cell count (RNC) lack specificity in detecting appendicitis-related inflammation. N-glycosylation, an asparagine-linked glycosylation process, plays a vital role in cellular interactions, angiogenesis, immune response, and effector functions. Altered N-glycosylation impacts tumor growth and both acute and chronic inflammatory processes. IgG, the second most abundant glycoprotein in serum, shows altered glycosylation patterns during inflammation, suggesting that IgG glycan modifications may serve as potential biomarkers for appendicitis. Specifically, increased levels of agalactosylated IgG glycans are a known feature of various inflammatory conditions, potentially including appendicitis. Identifying pediatric appendicitis remains challenging due to the absence of specific biomarkers, which makes diagnosis reliant on clinical symptoms, imaging such as ultrasound, and nonspecific lab indicators (e.g., CRP, WBC, ANC). In this study, we analyzed the IgG derived N-glycome in pediatric patients with appendicitis compared with healthy controls. Methodology: The N-glycome was analyzed by high-performance liquid-chromatography combined with mass spectrometry. IgG was isolated from serum samples by Protein G column. The IgG derived glycans were released by enzymatic deglycosylation and fluorescent tags were attached to each glycan moiety, which made necessitates the sample clean-up for further reliable quantitation. Overall, 38 controls and 40 serum samples diagnosed with pediatric appendicitis were analyzed by HILIC-MS methods. Multivariate statistical tests were performed with area percentage under the peak data derived from the integrated peaks, which were obtained from the chromatograms. Conclusions: Our results represented the altered N-glycome of IgG in pediatric appendicitis is similar with other observations. The glycosylation pattern reported so far for IgG is characterized by decreased galactosylation and sialylation, and an increase in fucosylation.

Keywords: N-glycosylation, liquid chromatography, mass spectrometry, inflammation, appendicitis, immunoglobulin G

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Authors: Ugo Rovigatti

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Neuroblastoma (NBL) has epitomized for at least 40 years our understanding of cancer cellular and molecular biology and its potential applications to novel therapeutic strategies. This includes the discovery of the very first oncogene aberrations and tumorigenesis suppression by differentiation in the 80s; the potential role of suppressor genes in the 90s; the relevance of immunotherapy in the millennium first, and the discovery of additional mutations by NGS technology in the millennium second decade. Similar discoveries were achieved in the majority of human cancers, and similar therapeutic interventions were obtained subsequently to NBL discoveries. Unfortunately, targeted therapies suggested by specific mutations (such as MYCN amplification –MNA- present in ¼ or 1/5 of cases) have not elicited therapeutic successes in aggressive NBL, where the prognosis is still dismal. The reasons appear to be linked to Tumor Heterogeneity, which is particularly evident in NBL but also a clear hallmark of aggressive human cancers generally. The new avenue of cancer immunotherapy (CIT) provided new hopes for cancer patients, but we still ignore the cellular or molecular targets. CIT is emblematic of high-risk disease (HR-NBL) since the mentioned GD2 passive immunotherapy is still providing better survival. We recently critically reviewed and evaluated the literature depicting the genomic landscapes of HR-NBL, coming to the qualified conclusion that among hundreds of affected genes, potential targets, or chromosomal sites, none correlated with anti-GD2 sensitivity. A better explanation is provided by the Micro-Foci inducing Virus (MFV) model, which predicts that neuroblasts infection with the MFV, an RNA virus isolated from a cancer-cluster (space-time association) of HR-NBL cases, elicits the appearance of MNA and additional genomic aberrations with mechanisms resembling chromothripsis. Neuroblasts infected with low titers of MFV amplified MYCN up to 100 folds and became highly transformed and malignant, thus causing neuroblastoma in young rat pups of strains SD and Fisher-344 and larger tumor masses in nu/nu mice. An association was discovered with GD2 since this glycosphingolipid is also the receptor for the family of MFV virus (dsRNA viruses). It is concluded that a dsRNA virus, MFV, appears to provide better explicatory mechanisms for the genesis of i) specific genomic aberrations such as MNA; ii) extensive tumor heterogeneity and chromothripsis; iii) the effects of passive immunotherapy with anti-GD2 monoclonals and that this and similar models should be further investigated in both pediatric and adult cancers.

Keywords: neuroblastoma, MYCN, amplification, viruses, GD2

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Authors: Xiaoping Su, Gabriel G. Malouf

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Introduction: Breast cancer is a heterogeneous disease that can be classified in 4 subgroups using transcriptional profiling. The role of lncRNA expression in human breast cancer biology, prognosis, and molecular classification remains unknown. Methods and results: Using an integrative comprehensive analysis of lncRNA, mRNA and DNA methylation in 900 breast cancer patients from The Cancer Genome Atlas (TCGA) project, we unraveled the molecular portraits of 1,700 expressed lncRNA. Some of those lncRNAs (i.e, HOTAIR) are previously reported and others are novel (i.e, HOTAIRM1, MAPT-AS1). The lncRNA classification correlated well with the PAM50 classification for basal-like, Her-2 enriched and luminal B subgroups, in contrast to the luminal A subgroup which behaved differently. Importantly, estrogen receptor (ESR1) expression was associated with distinct lncRNA networks in lncRNA clusters III and IV. Gene set enrichment analysis for cis- and trans-acting lncRNA showed enrichment for breast cancer signatures driven by breast cancer master regulators. Almost two third of those lncRNA were marked by enhancer chromatin modifications (i.e., H3K27ac), suggesting that lncRNA expression may result in increased activity of neighboring genes. Differential analysis of gene expression profiling data showed that lncRNA HOTAIRM1 was significantly down-regulated in basal-like subtype, and DNA methylation profiling data showed that lncRNA HOTAIRM1 was highly methylated in basal-like subtype. Thus, our integrative analysis of gene expression and DNA methylation strongly suggested that lncRNA HOTAIRM1 should be a tumor suppressor in basal-like subtype. Conclusion and significance: Our study depicts the first lncRNA molecular portrait of breast cancer and shows that lncRNA HOTAIRM1 might be a novel tumor suppressor.

Keywords: lncRNA profiling, breast cancer, HOTAIRM1, tumor suppressor

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Authors: Neda Menbari, Ramin Mehdiabadi

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Background: breast cancer remains a critical global health issue, constituting a leading cause of cancer-related mortality in women. MicroRNAs (miRs) are natural RNA molecules that play an important role in cellular processes and regulate post-transcriptional gene expression. MiR-216b-5p is a miR that acts as a tumor suppressor. The expression levels of FoxM1 and miR-216b-5p in malignant and control cells have been evaluated by quantitative polymerase chain reaction (qPCR) technique and flow cytometry. Results: the results of this study revealed a significant downregulation of miR-216b-5p in cancerous cells compared to the control MCF-10A cells (P=0.0004). Interestingly, the expression of miR-216b-5p exhibited an inverse relationship with key clinical indicators such as tumor size, grade, and lymph node invasion. Conclusion: The study's findings showed the prognostic value of miR-216b-5p levels in breast cancer, and its reduced expression correlates with unfavorable tumor characteristics. This research recommends performing more studies on the role of FoxM1 and miR-216b-5p in breast cancer pathology which potentially paving the way for targeted therapeutic interventions.

Keywords: breast cancer, gene expression, FOXM1, microRNA

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Authors: Mai Ali

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Advancing beyond the junior stage of a paediatrician’s career is a crucial step where they accumulate essential skills and knowledge. This process prepares them for the challenges they'll encounter throughout their profession, particularly in dealing with paediatric emergencies. This can be especially demanding for trainees specializing in fields like endocrinology, particularly in the management of Diabetic Ketoacidosis (DKA) in the UK. In different societal contexts, junior doctors, whether specializing in pediatrics or other medical fields, are generally expected to possess a fundamental level of knowledge and skills necessary for managing diabetic ketoacidosis (DKA) emergencies. These physicians consistently concurred in recognizing prevalent problems in the healthcare facilities they examined. Such issues include the lack of established guidelines for DKA treatment and the inadequate availability of comprehensive training opportunities. The abstract underscores the critical importance of junior paediatricians acquiring expertise in managing paediatric emergencies, with a specific focus on DKA. Commonly, issues like the lack of standardized protocols and training deficiencies are recurring themes across healthcare facilities. This research proposal aims to conduct a thematic analysis of the proficiency of paediatric trainees in the United Kingdom when handling DKA in various clinical contexts. The primary goal is to assess their competency and suggest effective strategies for comprehensive DKA training improvement.

Keywords: junior pediatrician, DKA, standardized protocols, level of competence

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