Visualization of collagen morphological changes in transition from tumor to normal tissue in breast cancer by multiphoton microscopy

2021 ◽  
Author(s):  
Yulan Liu ◽  
Yu Yi ◽  
Zhen Li ◽  
Zhenlin Zhan ◽  
Lianhuang Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Normal Tissue ◽  
Morphological Changes ◽  
Multiphoton Microscopy

scholarly journals Metformin induces Ferroptosis by inhibiting UFMylation of SLC7A11 in breast cancer

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Jingjing Yang ◽  
Yulu Zhou ◽  
Shuduo Xie ◽  
Ji Wang ◽  
Zhaoqing Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Treatment ◽  
Morphological Changes ◽  
Tumor Model ◽  
Independent Manner ◽  
Regulated Cell Death ◽  
Anti Cancer ◽  
Cancer Agent ◽  
Approved Drugs

Abstract Background Ferroptosis is a newly defined form of regulated cell death characterized by the iron-dependent accumulation of lipid peroxidation and is involved in various pathophysiological conditions, including cancer. Targeting ferroptosis is considered to be a novel anti-cancer strategy. The identification of FDA-approved drugs as ferroptosis inducers is proposed to be a new promising approach for cancer treatment. Despite a growing body of evidence indicating the potential efficacy of the anti-diabetic metformin as an anti-cancer agent, the exact mechanism underlying this efficacy has not yet been fully elucidated. Methods The UFMylation of SLC7A11 is detected by immunoprecipitation and the expression of UFM1 and SLC7A11 in tumor tissues was detected by immunohistochemical staining. The level of ferroptosis is determined by the level of free iron, total/lipid Ros and GSH in the cells and the morphological changes of mitochondria are observed by transmission electron microscope. The mechanism in vivo was verified by in situ implantation tumor model in nude mice. Results Metformin induces ferroptosis in an AMPK-independent manner to suppress tumor growth. Mechanistically, we demonstrate that metformin increases the intracellular Fe2+ and lipid ROS levels. Specifically, metformin reduces the protein stability of SLC7A11, which is a critical ferroptosis regulator, by inhibiting its UFMylation process. Furthermore, metformin combined with sulfasalazine, the system xc− inhibitor, can work in a synergistic manner to induce ferroptosis and inhibit the proliferation of breast cancer cells. Conclusions This study is the first to demonstrate that the ability of metformin to induce ferroptosis may be a novel mechanism underlying its anti-cancer effect. In addition, we identified SLC7A11 as a new UFMylation substrate and found that targeting the UFM1/SLC7A11 pathway could be a promising cancer treatment strategy.

scholarly journals Clinical assessement of the 8 genes on chromosome 3 with also MGMT gene promoter regions methylaton status in patients with breast cancer luminal hystotype

2017 ◽  
Vol 16 (4) ◽  
pp. 38-45
Author(s):  
D. A. Ryabchikov ◽  
I. K. Vorotnikov ◽  
T. P. Kazubskaya ◽  
S. S. Lukina ◽  
E. A. Filippova ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Polymerase Chain Reaction ◽  
Normal Tissue ◽  
Methylation Status ◽  
Chromosome 3 ◽  
Epigenetic Changes ◽  
Chain Reaction ◽  
Promoter Regions ◽  
Polymerase Chain

Background. Epigenetic changes of TSG are supposed as the most fine and active genes regulation mechanism in particular breast cancer (BC) genes pathway development. The most valuable results are awaited for methylation role of genes located on the short arm of chromosome 3 with also MGMT gene (10q26) in BC pathogenesis because of their ambiguous data for methylation status in tumors. Objective: to illustrate the specific methylation role of the RASSF1A, SEMA3B, RARß2, RHOA, GPX1, USP4, DAG1, NKIRAS1 and MGMT genes promoter regions in BC pathogenesis. Materials and methods. Sample set of 174 BC patients consists of tumor and surrounding histologically normal tissue that were collected and clinically characterized in the N.N. Blokhin National Medical Research Center of Oncology. Two substantive methods were used to evaluate DNA methylation status. To analyse RASSF1A, SEMA3B, RARß2 and MGMT genes methylation we used polymerase chain reaction specific for the methylated allele. Whereas for analyses RHOA, GPX1, USP4, DAG1, NKIRAS1 promoter regions genes methylation status was used methyl sensitive restriction analyses with 2 methyl sensitive endonuclaeses HpaII and HhaI with subsequent polymerase chain reaction. Results. A statistically significant high frequency of RASSF1A, SEMA3B, RARß2, and MGMT genes methylation in epithelial breast tumors compared with histologically normal tissue from the same patients was shown. Significant correlation of RARß2 and MGMT genes methylation frequency considering the different clinical and morphological characteristics of the malignant process was revealed. The statistically significant relationship between methylation of RASSF1A, RARß2 and MGMT genes and patient survival is shown for the first time. Conclusion. The findings of epigenetic changes in the luminal BC supplement the “molecular picture” of this cancer and contribute to an understanding of its pathogenesis. The revealed features of investigated genes methylation can find clinical application for the development of modern approaches to prognosis, prevention and choice of tactics for treatment of BC in females of the Moscow region.

scholarly journals Radionuclide-Based Imaging of Breast Cancer: State of the Art

Cancers ◽  
2021 ◽  
Vol 13 (21) ◽  
pp. 5459
Author(s):  
Huiling Li ◽  
Zhen Liu ◽  
Lujie Yuan ◽  
Kevin Fan ◽  
Yongxue Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Molecular Imaging ◽  
Single Photon ◽  
Morphological Changes ◽  
Imaging Techniques ◽  
Rapid Development ◽  
Photon Emission ◽  
Emission Computed Tomography ◽  
Biological Processes ◽  
Functional Perspective

Breast cancer is a malignant tumor that can affect women worldwide and endanger their health and wellbeing. Early detection of breast cancer can significantly improve the prognosis and survival rate of patients, but with traditional anatomical imagine methods, it is difficult to detect lesions before morphological changes occur. Radionuclide-based molecular imaging based on positron emission tomography (PET) and single-photon emission computed tomography (SPECT) displays its advantages for detecting breast cancer from a functional perspective. Radionuclide labeling of small metabolic compounds can be used for imaging biological processes, while radionuclide labeling of ligands/antibodies can be used for imaging receptors. Noninvasive visualization of biological processes helps elucidate the metabolic state of breast cancer, while receptor-targeted radionuclide molecular imaging is sensitive and specific for visualization of the overexpressed molecular markers in breast cancer, contributing to early diagnosis and better management of cancer patients. The rapid development of radionuclide probes aids the diagnosis of breast cancer in various aspects. These probes target metabolism, amino acid transporters, cell proliferation, hypoxia, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), gastrin-releasing peptide receptor (GRPR) and so on. This article provides an overview of the development of radionuclide molecular imaging techniques present in preclinical or clinical studies, which are used as tools for early breast cancer diagnosis.

ANTICANCER POTENTIAL OF PLANT EXTRACTS FROM RIYADH (SAUDI ARABIA) ON MDA-MB-231 BREAST CANCER CELLS

2018 ◽  
Vol 15 (4) ◽  
pp. 46 ◽  
Author(s):  
Fahd A. Nasr ◽  
Nael Abutaha ◽  
Mohammad Al-Zahrani ◽  
Muhammad Farooq ◽  
Mohammad A Wadaan
Keyword(s):  
Breast Cancer ◽  
Saudi Arabia ◽  
Medicinal Plants ◽  
Traditional Medicine ◽  
Anticancer Activity ◽  
Cancer Cells ◽  
Anticancer Agents ◽  
Breast Cancer Cells ◽  
Morphological Changes ◽  
Cell Integrity

Background: Medicinal plants have been used in traditional medicine for the treatment of numerous diseases worldwide. There is a dire need for new anticancer agents and plants used in traditional medicine are a particularly useful source. Materials and methods: In this study, extracts of five different plants that grow in the desert of Saudi Arabia were evaluated to assess their cytotoxicity against the MDA-MB-231 breast cancer cell line. Soxhlet extraction was carried out on the leaves and stems using different solvents. The cytotoxicity of these extracts against MDA-MB-231 breast cancer cells was assessed using the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays. The apoptotic cellular morphological changes were observed using inverted and fluorescence microscopes. Results: Our results showed that two of the five different medicinal plants (Rumex vesicarius and Malva parviflora) exhibited strong anticancer activity against the breast cancer cells. Specifically, 2 of the 40 extracts (from the five studied plants) showed promising activity. The chloroform extract of the stem of R. vesicarius (RSV CHCL3) exhibited moderate anticancer activity with a half-maximal inhibitory concentration (IC50) of 230 µg/mL while that of the hexane extract of M. parviflora stems (MPS Hex) was 248 µg/mL. Loss of cell integrity, shrinkage of the cytoplasm, and cell detachment were observed in the extract-treated MDA-MB-231 cells. Conclusion: R. vesicarius and M. parviflora chloroform and n-hexane stem extracts showed significant cytotoxicity against MDA-MB-231 human breast carcinoma cells.

scholarly journals MMP1, MMP9, and COX2 Expressions in Promonocytes Are Induced by Breast Cancer Cells and Correlate with Collagen Degradation, Transformation-Like Morphological Changes in MCF-10A Acini, and Tumor Aggressiveness

2013 ◽  
Vol 2013 ◽  
pp. 1-15 ◽  
Author(s):  
G. K. Chimal-Ramírez ◽  
N. A. Espinoza-Sánchez ◽  
D. Utrera-Barillas ◽  
L. Benítez-Bribiesca ◽  
J. R. Velázquez ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Immune Cells ◽  
Immune Cell ◽  
Morphological Changes ◽  
Tumor Stroma ◽  
Collagen Degradation ◽  
Tumor Aggressiveness ◽  
Soluble Factors ◽  
Immune Effector

Tumor-associated immune cells often lack immune effector activities, and instead they present protumoral functions. To understand how tumors promote this immunological switch, invasive and noninvasive breast cancer cell (BRC) lines were cocultured with a promonocytic cell line in a Matrigel-based 3D system. We hypothesized that if communication exists between tumor and immune cells, coculturing would result in augmented expression of genes associated with tumor malignancy. Upregulation of proteasesMMP1andMMP9and inflammatoryCOX2genes was found likely in response to soluble factors. Interestingly, changes were more apparent in promonocytes and correlated with the aggressiveness of the BRC line. Increased gene expression was confirmed by collagen degradation assays and immunocytochemistry of prostaglandin 2, a product of COX2 activity. Untransformed MCF-10A cells were then used as a sensor of soluble factors with transformation-like capabilities, finding that acini formed in the presence of supernatants of the highly aggressive BRC/promonocyte cocultures often exhibited total loss of the normal architecture. These data support that tumor cells can modify immune cell gene expression and tumor aggressiveness may importantly reside in this capacity. Modeling interactions in the tumor stroma will allow the identification of genes useful as cancer prognostic markers and therapy targets.

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