scholarly journals Nanosized zinc, epigenetic changes and its relationship with DMBA induced breast cancer in rats

2020 ◽  
Vol 39 (1) ◽  
pp. 200-208
Author(s):  
Barbara Bobrowska-Korczak ◽  
Kamila Domanska ◽  
Dorota Skrajnowska ◽  
Robert Wrzesien ◽  
Joanna Giebultowicz ◽  
...  

Abstract The aim of the research was to compare the impact of nano- and micro-sized-zinc on the kinetics of changes in the level of 3-methyladenine, 7-methylguanine, 7-methylguanosine, O-methylguanosine, 1-methyladenosine, N6-methyl-2’-deoxyguanosine in urine of rats with breast cancer. Female Sprague-Dawley rats divided into 3 groups were used in the study. Animals were fed only a control diet or diets supplemented with the nano and micro-sized zinc particles. To induce the mammary cancer (adenocarcinoma), rats were treated with 7,12-dimethylbenz[a]anthracene (DMBA). Modified nucleosides were determined by a validated high performance liquid chromatography coupled to mass spectrometry method. In the first stage of investigations a synergistic activity of nanosized Zn with DMBA on the growth of the neoplastic process was found. During that time a statistically significant increase in the levels of all six examined markers in the rats’ urine was observed. However, as the experiment continued, the supplementation with nanosized zinc caused inhibition of tumour growth, being followed by regression and remission of tumours, as well as, a statistically significant systematic reduction of the levels of methyl derivatives in the urine. Biopsy images indicated grade 1 tumours with multiple inflammatory infiltrates in the group treated with zinc nanoparticles, whereas, in the other groups, moderately-differentiated grade 2 adenocarcinoma was identified. It was found that the biological activity of zinc depends on the size of applied particles, as the treatment with zinc microparticles has not had much effect on cancer progression.

2021 ◽  
Vol 17 (3) ◽  
pp. e1008819
Author(s):  
Héctor Climente-González ◽  
Christine Lonjou ◽  
Fabienne Lesueur ◽  
Dominique Stoppa-Lyonnet ◽  
Nadine Andrieu ◽  
...  

Genome-wide association studies (GWAS) explore the genetic causes of complex diseases. However, classical approaches ignore the biological context of the genetic variants and genes under study. To address this shortcoming, one can use biological networks, which model functional relationships, to search for functionally related susceptibility loci. Many such network methods exist, each arising from different mathematical frameworks, pre-processing steps, and assumptions about the network properties of the susceptibility mechanism. Unsurprisingly, this results in disparate solutions. To explore how to exploit these heterogeneous approaches, we selected six network methods and applied them to GENESIS, a nationwide French study on familial breast cancer. First, we verified that network methods recovered more interpretable results than a standard GWAS. We addressed the heterogeneity of their solutions by studying their overlap, computing what we called the consensus. The key gene in this consensus solution was COPS5, a gene related to multiple cancer hallmarks. Another issue we observed was that network methods were unstable, selecting very different genes on different subsamples of GENESIS. Therefore, we proposed a stable consensus solution formed by the 68 genes most consistently selected across multiple subsamples. This solution was also enriched in genes known to be associated with breast cancer susceptibility (BLM, CASP8, CASP10, DNAJC1, FGFR2, MRPS30, and SLC4A7, P-value = 3 × 10−4). The most connected gene was CUL3, a regulator of several genes linked to cancer progression. Lastly, we evaluated the biases of each method and the impact of their parameters on the outcome. In general, network methods preferred highly connected genes, even after random rewirings that stripped the connections of any biological meaning. In conclusion, we present the advantages of network-guided GWAS, characterize their shortcomings, and provide strategies to address them. To compute the consensus networks, implementations of all six methods are available at https://github.com/hclimente/gwas-tools.


2020 ◽  
Vol 7 (4) ◽  
pp. 124 ◽  
Author(s):  
Jun Yang ◽  
Gokhan Bahcecioglu ◽  
Pinar Zorlutuna

Emerging evidence has shown multiple roles of the tumor microenvironment (TME) components, specifically the extracellular matrix (ECM), in breast cancer development, progression, and metastasis. Aside from the biophysical properties and biochemical composition of the breast ECM, the signaling molecules are extremely important in maintaining homeostasis, and in the breast TME, they serve as the key components that facilitate tumor progression and immune evasion. Extracellular vesicles (EVs), the mediators that convey messages between the cells and their microenvironment through signaling molecules, have just started to capture attention in breast cancer research. In this comprehensive review, we first provide an overview of the impact of ECM in breast cancer progression as well as the alterations occurring in the TME during this process. The critical importance of EVs and their biomolecular contents in breast cancer progression and metastasis are also discussed. Finally, we discuss the potential biomedical or clinical applications of these extracellular components, as well as how they impact treatment outcomes.


2019 ◽  
Vol 10 ◽  
Author(s):  
Dominika Stygar ◽  
Dorian Andrare ◽  
Barbara Bażanów ◽  
Elżbieta Chełmecka ◽  
Tomasz Sawczyn ◽  
...  

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
O. Merino ◽  
R. Sánchez ◽  
B. M. Gregorio ◽  
F. J. Sampaio ◽  
J. Risopatrón

Obesity has adverse effects on male fertility and usually is diagnosed with a prevalence of vitamin D deficiency (VD-). Discussion on the impact of obesity/VD- on sperm function has been limited. This study analyzed the effects of diet-induced obesity/VD- on viability and plasma membrane integrity (PMI), superoxide anion (O2-) level, and DNA fragmentation (DNAfrag) in sperm Sprague-Dawley rats. The males were randomized into four groups and fed for a period of 12 weeks: G1: control diet with vitamin D (C/VD+), G2: control diet without vitamin D (C/VD-), G3: high-fat diet with vitamin D (HF/VD+), and G4: high-fat diet without vitamin D (HF/VD-). Sperm function parameters were analyzed by flow cytometry. PMI percentages and O2- levels were not affected by any of the diets. DNA fragmentation was increasing significantly (p<0.05) in the spermatozoa of animals with diets vitamin D deficient (G2) and diet-induced obesity (G4). Our results allow us to point out that diet-induced obesity and VD- produce greater damage in DNA sperm of rats. The use of nutraceuticals containing vitamin D could be reducing the risk of fragmentation of DNA in spermatozoa.


F1000Research ◽  
2021 ◽  
Vol 10 ◽  
pp. 902
Author(s):  
Kusmardi Kusmardi ◽  
Elvan Wiyarta ◽  
Numlil Khaira Rusdi ◽  
Andi Muh. Maulana ◽  
Ari Estuningtyas ◽  
...  

Background: Research in natural substances for their anticancer potential has become increasingly popular. Lunasin, a soybean protein, is known to inhibit cancer progression via various pathways.  The aim of this study was to investigate the effect of Lunasin Extract (LE) on the expression of Intercellular Adhesion Molecule 1 (ICAM-1) and epithelial cadherins (E-Cadherin) in breast cancer. Methods: In this true-experimental in vivo study, 24 Sprague-Dawley rats that were induced by 7,12-Dimethylbenz[a]anthracene (DMBA), were used. Based on the therapy given, the groups were divided into, normal, positive control (PC), negative control (NC), adjuvant, curative, and preventive. Lunasin was extracted from soybean seeds of the Grobogan variety in Indonesia. Tissue samples were obtained, processed, stained with anti-ICAM-1 and anti-E-Cadherin antibodies, examined under a microscope, and quantified using H-score. The data were analyzed using ANOVA, which was then followed by Duncan's test. Results: Statistically significant difference in ICAM-1 expression was observed between the following groups: adjuvant and NC, normal and NC, PC and NC, adjuvant and preventive, normal and preventive, PC and preventive, adjuvant and curative, normal and curative, PC and curative. E-Cadherin expression was significantly different between preventive and NC, adjuvant and NC, PC and NC, normal and NC, adjuvant and curative, PC and curative, normal and curative, normal and preventive. Significant negative correlation was found between ICAM-1 and E-Cadherin [-0.616 (-0.8165; -0.283)] with p = 0.001. Conclusion: Preventive dose of LE was able to reduce ICAM-1 expression while increasing E-Cadherin expression.


2017 ◽  
Author(s):  
Rosa Puigpinos-Riera ◽  
Xavier Continente ◽  
Gemma Serral ◽  
Xavi Bargalló ◽  
Montserrat Doménech ◽  
...  

BACKGROUND Breast cancer continues to be the most commonly diagnosed cancer in women. Breast cancer survivors face numerous problems, especially after completing the first year of intense treatment. We present the protocol for an ongoing study to analyze the impact of a series of factors on breast cancer survival related to lifestyle, emotional well-being, and use of complementary and alternative medicine (CAM). OBJECTIVE We aim to analyze the influence of social determinants, lifestyle changes, emotional well-being, and use of CAM in the progression of breast cancer in women diagnosed with breast cancer between 2003 and 2013 in Barcelona, Spain. METHODS We will perform a mixed cohort study (prospective and retrospective) of women diagnosed with breast cancer, created using a convenience sample in which we study the evolution of the disease (relapse, death, or remaining disease-free). Once identified, we sent the women information about the study and an informed consent form that they are required to sign in order to participate; a total of 2235 women were recruited. We obtained the following information from all participants: sociodemographic profile via a phone interview, and a self-administered survey of information about the study’s objectives (lifestyles, emotional well-being, health care services, and the use of CAM). Lastly, we examined clinical records to obtain data on the tumor at the time of diagnosis, the treatment received, the occurrence of relapses (if any), and the tumor typology. We present data on the women’s social profile based on descriptive data obtained from the telephone interview (welcome survey). RESULTS Based on the welcome survey, which was completed by 2712 women, 14.42% (391/2712) of respondents were <50 years of age, 45.50% (1234/2712) were between 50 and 65 years of age, and 40.08% (1087/2712) were >65 years of age. A total of 43.69% (1185/2712) belonged to the highest social classes (I and II), 31.27% (848/2712) to the middle class (III), and 23.49% (637/2712) to the working classes (IV and V). Approximately 22.71% (616/2712) lived alone, 38.31% (1039/2712) lived with one person, and 38.97% (1057/2712) lived with two or more people. CONCLUSIONS We obtained information from a large cohort of women, but this study has limitations related to the convenience sampling strategy, one of which is reduced representativeness. Conversely, being a self-administered survey, the study introduces biases, especially from respondents that answered on paper. However, the information that the study provides will serve as the basis for designing future interventions aimed at improving the knowledge gaps indicated for women with breast cancer.


Author(s):  
David Licha ◽  
Silvia Vidali ◽  
Sepideh Aminzadeh-Gohari ◽  
Oliver Alka ◽  
Leander Breitkreuz ◽  
...  

Ketogenic diet (KD) is getting in the focus as auxiliary cancer therapy, since it provides sufficient energy supply for healthy cells, while impairing energy production in tumor cells underlying the Warburg effect. Thereby, it can assist in inhibiting tumor growth and simultaneously counteract cachexia, which is frequently observed in cancer patients under chemotherapy. In order to provide molecular evidence for the proposed synergistic inhibition of tumor growth, we applied untargeted quantitative metabolome analysis on a breast cancer xenograft mouse model. Healthy mice and such bearing breast cancer xenografts and receiving chemotherapy were compared after treatment with control diet and KD. Metabolomic profiling was performed on plasma samples, applying high-performance liquid chromatography coupled to tandem mass spectrometry. Statistical analysis revealed metabolic fingerprints comprising numerous significantly regulated features in the group of mice bearing breast cancer. This fingerprint disappeared after treatment with KD, resulting in recovery to the metabolic status observed in healthy mice receiving control diet. Moreover, amino acid metabolism as well as fatty acid transport were found to be affected by both, the tumor and the applied KD. Our results provide clear evidence of a significant molecular effect of KD in the context of tumor growth inhibition.


Author(s):  
Aleksandra Markiewicz ◽  
Justyna Topa ◽  
Marta Popęda ◽  
Jolanta Szade ◽  
Jarosław Skokowski ◽  
...  

Breast cancer (BC) is a heterogeneous disease with different molecular subtypes, which can be defined by oestrogen (ER), progesterone (PR) and human epidermal growth factor (HER2) receptors’ status as luminal, HER2+ and triple negative (TNBC). Molecular subtypes also differ in their epithelial-mesenchymal phenotype, which might be related to their aggressiveness, as activation of the epithelial-mesenchymal transition (EMT) is linked with increased ability of cancer cells to survive and metastasize. Nevertheless, the reverse process of mesenchymal-epithelial transition was shown to be required to sustain metastatic colonization. In this study we aimed to analyse activation of the EMT process in primary tumours (PT), which have (N+) or have not (N–) colonized the lymph nodes, as well as the lymph nodes metastases (LNM) themselves in 88 BC patients. We showed that luminal N– PT have the lowest activation of the EMT process (27%), in comparison to N+ PT (48%, p=0.06). On the other hand, TNBC do not show statistically significant EMT activation at the stage before lymph colonization (N–, 83%) and after colonization of the lymph nodes (N+, 63%, p=0.58). TNBC are also the least plastic (unable to change the EMT phenotype) in terms of turning EMT on or off between matched PT and LNM (0% EMT plasticity in TNBC vs 36% plasticity in luminal tumours). Moreover, in TNBC activation of EMT was correlated with increased cell division rate of the PT– in mesenchymal TNBC PT median Ki-67 was 45% in comparison to 10% in epithelial TNBC PT (p=0.002), whereas in PT of luminal subtypes Ki-67 did not differ between epithelial and mesenchymal phenotypes. Profiling of immunotranscriptome of epithelial and mesenchymal luminal BC with Nanostring technology revealed that N– PT with epithelial phenotype were enriched in inflammatory response signatures, whereas N+ mesenchymal cancers showed elevated MHC class II antigen presentation. Overall, activation of EMT changes during cancer progression and metastatic colonization of the lymph nodes depending on the PT molecular subtype and is related to differences in stromal signatures. Activation of EMT is associated with colonizing phenotype in luminal PT and proliferative phenotype of TNBC.


2019 ◽  
Vol 2019 ◽  
pp. 1-10
Author(s):  
Olayide Agodirin ◽  
Samuel Olatoke ◽  
Ganiyu Rahman ◽  
Julius Olaogun ◽  
Oladapo Kolawole ◽  
...  

Background. Reports are scanty on the impact of long primary care interval in breast cancer. Exploratory reports in Nigeria and other low-middle-income countries suggest detrimental impact. The primary aim was to describe the impact of long primary care interval on breast cancer progression, and the secondary aim was to describe the factors perceived by patients as the reason(s) for long intervals. Method. Questionnaire-based survey was used in 9 Nigerian tertiary institutions between May 2017 and July 2018. The study hypothesis was that the majority of patients stayed >30 days, and the majority experienced stage migration in primary care interval. Assessment of the impact of the length of interval on tumor stage was done by survival analysis technique, and clustering analysis was used to find subgroups of the patient journey. Results. A total of 237 patients presented to primary care personnel with tumor ≤5cm (mean 3.4±1.2cm). A total of 151 (69.3%, 95% CI 62.0-75.0) stayed >30 days in primary care interval. Risk of stage migration in primary care interval was 49.3% (95% CI 42.5%-56.3%). The most common reasons for long intervals were symptom misinformation and misdiagnosis. Clustering analysis showed 4 clusters of patients’ experience and journey: long interval due to distance, long interval due to misinformation, long interval due to deliberate delaying, and not short interval—prepared for treatment. Conclusion. The majority of patients stayed longer than 30 days in primary care interval. Long primary care interval was associated with a higher risk of stage migration, and more patients reported misinformation and misdiagnosis as reasons for a long interval.


Author(s):  
Samaneh Salafzoon ◽  
Hamideh Mahmoodzadeh Hosseini ◽  
Raheleh Halabian

AbstractBackgroundAbnormal metabolism is a common event in cancerous cells. For example, the increase of reactive oxygen species (ROS) production, particularly due to aerobic respiration during invasive stage, results in cancer progression. Herein, the impact of kombucha tea prepared from ginger on the alteration of antioxidant agents was assessed in the breast cancer animal model.MethodsTwo types of kombucha tea with or without ginger were administered to BALB/c mice before and after tumor challenge. Superoxide dismutase (SOD), catalase, glutathione (GSH) and malondialdehyde (MDA) were evaluated in tumor, liver and kidney.ResultsAdministration of kombucha ginger tea significantly decreased catalase activity as well as GSH and MDA level in tumor homogenate (p<0.001). A significant decrease in SOD activity and increase in MDA quantity was determined in the kidney which had received kombucha ginger tea (pConclusionsThe consumption of kombucha prepared from ginger could exert minor antioxidant impacts by balancing multi antioxidant factors in different tissues in the breast cancer models.


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