scholarly journals Potential effect of probiotics in the treatment of breast cancer

2019 ◽  
Vol 13 (2) ◽  
Author(s):  
Luis Mendoza
Keyword(s):  
Breast Cancer ◽  
Large Scale ◽  
Molecular Mechanisms ◽  
Potential Role ◽  
Potential Effect ◽  
Current Review ◽  
Gastrointestinal Bacteria ◽  
The World

Breast cancer is one of the most important causes of cancerrelated morbidity and mortality in the world. Probiotics, as functional food, have the potential to act against breast cancer, as evidenced by cell-based and animal model experiments. Probiotic may be useful in prevention or treatment of breast cancer by modulating the gastrointestinal bacteria and the systemic immune system. However, large-scale clinical trials and intensive research are mandatory to confirm the in vitro and in vivo results and exploring the probiotics-related metabolic, immune, and molecular mechanisms in breast cancer. This current review summarizes the available data related to probiotics and their potential role in the treatment of breast cancer.

scholarly journals Dihydroartemisinin prevents breast cancer-induced osteolysis via inhibiting both breast caner cells and osteoclasts

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Ming-Xuan Feng ◽  
Jian-Xin Hong ◽  
Qiang Wang ◽  
Yong-Yong Fan ◽  
Chi-Ting Yuan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Resorption ◽  
Molecular Mechanisms ◽  
Osteoclast Differentiation ◽  
Metastatic Breast ◽  
Osteoclast Formation ◽  
Migration And Invasion ◽  
Titanium Particle

Abstract Bone is the most common site of distant relapse in breast cancer, leading to severe complications which dramatically affect the patients’ quality of life. It is believed that the crosstalk between metastatic breast cancer cells and osteoclasts is critical for breast cancer-induced osteolysis. In this study, the effects of dihydroartemisinin (DHA) on osteoclast formation, bone resorption, osteoblast differentiation and mineralization were initially assessed in vitro, followed by further investigation in a titanium-particle-induced osteolysis model in vivo. Based on the proved inhibitory effect of DHA on osteolysis, DHA was further applied to MDA-MB-231 breast cancer-induced mouse osteolysis model, with the underlying molecular mechanisms further investigated. Here, we verified for the first time that DHA suppressed osteoclast differentiation, F-actin ring formation and bone resorption through suppressing AKT/SRC pathways, leading to the preventive effect of DHA on titanium-particle-induced osteolysis without affecting osteoblast function. More importantly, we demonstrated that DHA inhibited breast tumor-induced osteolysis through inhibiting the proliferation, migration and invasion of MDA-MB-231 cells via modulating AKT signaling pathway. In conclusion, DHA effectively inhibited osteoclastogenesis and prevented breast cancer-induced osteolysis.

scholarly journals Dissecting Breast Cancer Circulating Tumor Cells Competence via Modelling Metastasis in Zebrafish

2021 ◽  
Vol 22 (17) ◽  
pp. 9279
Author(s):  
Inés Martínez-Pena ◽  
Pablo Hurtado ◽  
Nuria Carmona-Ule ◽  
Carmen Abuín ◽  
Ana Belén Dávila-Ibáñez ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Molecular Mechanisms ◽  
Zebrafish Embryo ◽  
Cancer Metastasis ◽  
Fluid Shear Stress ◽  
In Vivo Models

Background: Cancer metastasis is a deathly process, and a better understanding of the different steps is needed. The shedding of circulating tumor cells (CTCs) and CTC-cluster from the primary tumor, its survival in circulation, and homing are key events of the metastasis cascade. In vitro models of CTCs and in vivo models of metastasis represent an excellent opportunity to delve into the behavior of metastatic cells, to gain understanding on how secondary tumors appear. Methods: Using the zebrafish embryo, in combination with the mouse and in vitro assays, as an in vivo model of the spatiotemporal development of metastases, we study the metastatic competency of breast cancer CTCs and CTC-clusters and the molecular mechanisms. Results: CTC-clusters disseminated at a lower frequency than single CTCs in the zebrafish and showed a reduced capacity to invade. A temporal follow-up of the behavior of disseminated CTCs showed a higher survival and proliferation capacity of CTC-clusters, supported by their increased resistance to fluid shear stress. These data were corroborated in mouse studies. In addition, a differential gene signature was observed, with CTC-clusters upregulating cell cycle and stemness related genes. Conclusions: The zebrafish embryo is a valuable model system to understand the biology of breast cancer CTCs and CTC-clusters.

scholarly journals CLDN6 Suppresses c–MYC–Mediated Aerobic Glycolysis to Inhibit Proliferation by TAZ in Breast Cancer

2021 ◽  
Vol 23 (1) ◽  
pp. 129
Author(s):  
Huinan Qu ◽  
Da Qi ◽  
Xinqi Wang ◽  
Yuan Dong ◽  
Qiu Jin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Molecular Mechanisms ◽  
Aerobic Glycolysis ◽  
Lactate Production ◽  
Suppressor Gene ◽  
Binding Motif ◽  
Cancer Proliferation ◽  
In Vivo Experiments

Claudin 6 (CLDN6) was found to be a breast cancer suppressor gene, which is lowly expressed in breast cancer and inhibits breast cancer cell proliferation upon overexpression. However, the mechanism by which CLDN6 inhibits breast cancer proliferation is unclear. Here, we investigated this issue and elucidated the molecular mechanisms by which CLDN6 inhibits breast cancer proliferation. First, we verified that CLDN6 was lowly expressed in breast cancer tissues and that patients with lower CLDN6 expression had a worse prognosis. Next, we confirmed that CLDN6 inhibited breast cancer proliferation through in vitro and in vivo experiments. As for the mechanism, we found that CLDN6 inhibited c–MYC–mediated aerobic glycolysis based on a metabolomic analysis of CLDN6 affecting cellular lactate levels. CLDN6 interacted with a transcriptional co–activator with PDZ-binding motif (TAZ) and reduced the level of TAZ, thereby suppressing c–MYC transcription, which led to a reduction in glucose uptake and lactate production. Considered together, our results suggested that CLDN6 suppressed c–MYC–mediated aerobic glycolysis to inhibit the proliferation of breast cancer by TAZ, which indicated that CLDN6 acted as a novel regulator of aerobic glycolysis and provided a theoretical basis for CLDN6 as a biomarker of progression in breast cancer.

scholarly journals Potent germline-like monoclonal antibodies: Rapid identification of promising candidates for antibody-based antiviral therapy

2021 ◽  
Author(s):  
Xiaoyi Zhu ◽  
Fei Yu ◽  
Yanling Wu ◽  
Tianlei Ying
Keyword(s):  
Monoclonal Antibodies ◽  
Rational Design ◽  
Large Scale ◽  
Molecular Mechanisms ◽  
Viral Infections ◽  
Somatic Hypermutation ◽  
Affinity Maturation ◽  
Human Mabs

Abstract Recent years, fully human monoclonal antibodies (mAbs) are making up an increasing share of the pharmaceutical market. However, to improve affinity and efficacy of antibodies, many somatic hypermutation could be introduced during affinity maturation, which cause several issues including safety and efficacy and limit their application in clinic. Here, we propose a special class of human mAbs with limited level of somatic mutations, referred to as germline-like mAbs. Remarkably, germline-like mAbs could have high affinity and potent neutralizing activity in vitro and in various animal models, despite lacking of extensive affinity maturation. Furthermore, the germline nature of these mAbs implies that they exhibit lower immunogenicity and can be elicited relatively fast in vivo compared with highly somatically mutated antibodies. In this review, we summarize germline-like mAbs with strong therapeutic and protection activity against various viruses that caused large-scale outbreaks in the last decade, including influenza virus H7N9, Zika virus (ZIKV), Dengue virus (DENV), Middle East respiratory syndrome coronavirus (MERS-CoV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We also illustrate underlying molecular mechanisms of these germline-like antibodies against viral infections from the structural and genetic perspective, thus providing insight into further development as therapeutic agents for treatment of infectious diseases and implication for rational design of effective vaccines.

scholarly journals Identification of MFGE8 and KLK5/7 as mediators of breast tumorigenesis and resistance to COX-2 inhibition

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Jun Tian ◽  
Vivian Wang ◽  
Ni Wang ◽  
Baharak Khadang ◽  
Julien Boudreault ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Molecular Mechanisms ◽  
Gene Knockout ◽  
In Silico Analysis ◽  
Breast Tumorigenesis ◽  
Clinical Benefits ◽  
Cox 2 ◽  
Cox 2 Inhibitors

Abstract Background Cyclooxygenase 2 (COX-2) promotes stemness in triple negative breast cancer (TNBC), highlighting COX-2 as a promising therapeutic target in these tumors. However, to date, clinical trials using COX-2 inhibitors in breast cancer only showed variable patient responses with no clear significant clinical benefits, suggesting underlying molecular mechanisms contributing to resistance to COX-2 inhibitors. Methods By combining in silico analysis of human breast cancer RNA-seq data with interrogation of public patient databases and their associated transcriptomic, genomic, and clinical profiles, we identified COX-2 associated genes whose expression correlate with aggressive TNBC features and resistance to COX-2 inhibitors. We then assessed their individual contributions to TNBC metastasis and resistance to COX-2 inhibitors, using CRISPR gene knockout approaches in both in vitro and in vivo preclinical models of TNBC. Results We identified multiple COX-2 associated genes (TPM4, RGS2, LAMC2, SERPINB5, KLK7, MFGE8, KLK5, ID4, RBP1, SLC2A1) that regulate tumor lung colonization in TNBC. Furthermore, we found that silencing MFGE8 and KLK5/7 gene expression in TNBC cells markedly restored sensitivity to COX-2 selective inhibitor both in vitro and in vivo. Conclusions Together, our study supports the establishment and use of novel COX-2 inhibitor-based combination therapies as future strategies for TNBC treatment.

scholarly journals MicroRNA-374b inhibits breast cancer progression through regulating CCND1 and TGFA genes

2021 ◽  
Author(s):  
Yan Liu ◽  
Ai Zhang ◽  
Ping-Ping Bao ◽  
Li Lin ◽  
Yina Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Breast Cancer Cells ◽  
Molecular Mechanisms ◽  
Breast Cancer Progression ◽  
Breast Cancer Cell Lines ◽  
Malignant Behavior

Abstract Emerging evidence indicates that microRNAs (miRNAs) play a critical role in breast cancer development. We recently reported that a higher expression of miR-374b in tumor tissues was associated with a better disease-free survival of triple-negative breast cancer (TNBC). However, the functional significance and molecular mechanisms underlying the role of miR-374b in breast cancer are largely unknown. In this current study, we evaluated the biological functions and potential mechanisms of miR-374b in both TNBC and non-TNBC. We found that miR-374b was significantly downregulated in breast cancer tissues, compared to adjacent tissues. MiR-374b levels were also lower in breast cancer cell lines, as compared to breast epithelial cells. In vitro and in vivo studies demonstrated that miR-374b modulates the malignant behavior of breast cancer cells, such as cell proliferation in 2D and 3D, cell invasion ability, colony forming ability, and tumor growth in mice. By using bioinformatics tools, we predicted that miR-374b plays a role in breast cancer cells through negatively regulating cyclin D1 (CCND1) and transforming growth factor alpha (TGFA). We further confirmed that CCND1 and TGFA contribute to the malignant behavior of breast cancer cells in vitro and in vivo. Our rescue experiments showed that overexpressing CCND1 or TGFA reverses the phenotypes caused by miR-374b overexpression. Taken together, our studies suggest that miR-374b modulates malignant behavior of breast cancer cells by negatively regulating CCND1 and TGFA genes. The newly identified miR-374b-mediated CCND1 and TGFA gene silencing may facilitate a better understanding of the molecular mechanisms of breast cancer progression.

scholarly journals Network models of primary melanoma microenvironments identify key melanoma regulators underlying prognosis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Won-Min Song ◽  
Praveen Agrawal ◽  
Richard Von Itter ◽  
Barbara Fontanals-Cirera ◽  
Minghui Wang ◽  
...  
Keyword(s):  
Large Scale ◽  
Molecular Mechanisms ◽  
Immune Cell ◽  
Primary Melanoma ◽  
Network Models ◽  
Transcriptional Networks ◽  
Melanoma Progression ◽  
Skin Malignancy

AbstractMelanoma is the most lethal skin malignancy, driven by genetic and epigenetic alterations in the complex tumour microenvironment. While large-scale molecular profiling of melanoma has identified molecular signatures associated with melanoma progression, comprehensive systems-level modeling remains elusive. This study builds up predictive gene network models of molecular alterations in primary melanoma by integrating large-scale bulk-based multi-omic and single-cell transcriptomic data. Incorporating clinical, epigenetic, and proteomic data into these networks reveals key subnetworks, cell types, and regulators underlying melanoma progression. Tumors with high immune infiltrates are found to be associated with good prognosis, presumably due to induced CD8+ T-cell cytotoxicity, via MYO1F-mediated M1-polarization of macrophages. Seventeen key drivers of the gene subnetworks associated with poor prognosis, including the transcription factor ZNF180, are tested for their pro-tumorigenic effects in vitro. The anti-tumor effect of silencing ZNF180 is further validated using in vivo xenografts. Experimentally validated targets of ZNF180 are enriched in the ZNF180 centered network and the known pathways such as melanoma cell maintenance and immune cell infiltration. The transcriptional networks and their critical regulators provide insights into the molecular mechanisms of melanomagenesis and pave the way for developing therapeutic strategies for melanoma.

scholarly journals SMC1A promotes tumor growth in breast cancer by activation of the AKT/FOXM1/STMN1 Signaling Pathway

2021 ◽  
Author(s):  
kaichun li ◽  
Ping Dai ◽  
Lin Xue ◽  
Long Liu ◽  
Shiyu Cheng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Molecular Mechanisms ◽  
Xenograft Model ◽  
Cell Cycle Checkpoints ◽  
Biological Functions ◽  
Tumor Tissues ◽  
Subcutaneous Xenograft ◽  
Novel Target

Abstract Background SMC1A (Structural maintenance of chromosomes 1) is overexpressed in various cancers and acts as an oncogene which has been implicated in critical biological functions (cell-cycle checkpoints regulation, cell division, and DNA repair). However, the mechanism and role of SMC1A in breast cancer are poorly understood. Methods TCGA database was utilized to explore the expression of SMC1A and the relationship between SMC1A and FOXM1 and STMN1. Subsequently, short hairpin RNA (shRNA) targeting SMC1A was used to examined the biological functions of it in MDA-MB-231 and MDA-MB-468 cells. Finally, subcutaneous xenograft model to verify the roles of SMC1A in vivo. Results In the present study, we demonstrated that SMC1A was significantly increased in breast cancer (BC) via TCGA database. Then loss and gain of function studies revealed that SMC1A contributed to BC cell survival, apoptosis, and invasion. Interestingly, we found that SMC1A triggered the AKT/FOXM1 cascade, which promoted BC cell proliferation. Furthermore, overexpression of FOXM1 abolished the inhibition of cell growth induced by SMC1A silencing in vitro. Clinically, the expression of SMC1A in BC tumor tissues is positively correlated with the expression of FOXM1. Conclusion Taken together, our findings not only enhanced our understanding of molecular mechanisms of SMC1A in BC, but also might provide a novel target for the development of therapeutic strategies.

scholarly journals GABRQ is Overexpressed and Correlated with Tumor Progression in Breast Cancer

2021 ◽  
Author(s):  
Ran Mei ◽  
Xichun Cui ◽  
Lili Zheng ◽  
Li Jingyi
Keyword(s):  
Breast Cancer ◽  
Molecular Mechanisms ◽  
Tumor Development ◽  
Bioinformatic Analysis ◽  
Gamma Aminobutyric Acid ◽  
Nude Mouse Model ◽  
Expression Levels ◽  
The Public

Abstract Background: Breast cancer (BRCA) is the most common type of women's cancer with a high incidence. The function of gamma-aminobutyric acid A receptor θ subunit (GABRQ) has been studied in other cancers. The results demonstrated that the expression levels of GABRQ were closely associated with tumor prognosis. However, the functions and mechanisms of GABRQ in BRCA remain unclear.Materials and methods: We used the public genome datasets and a tissue microarray (TMA) cohort to analyze the GABRQ expression levels. We performed Immunohistochemistry (IHC) and Western blot to determine GABRQ expression in BRCA cell lines and tissues. Cell proliferation was assessed by EDU assay and colony formation assay. Transwell assay was carried out to investigate the cell invasion ability in vitro and Xenograft nude mouse model was constructed to test the function of GABRQ on tumor growth in vivo. Moreover, we utilized bioinformatic analysis to identify the potential molecular mechanisms mediated by GABRQ modification in BRCA.Results: GABRQ was markedly up-regulated in BRCA tissues, and the expression levels of GABRQ were closely associated with BRCA prognosis. Functional analysis elucidated that knockdown of GABRQ could suppress BRCA cell growth and invasion in vitro, and inhibit tumor development in vivo. Moreover, we found that GABRQ overexpression activated the EMT signaling pathway.Conclusions: These results demonstrated that the function of GABRQ in BRCA progression provided potential prognostic predictors for BRCA patients.

scholarly journals TRIB1 regulates tumour growth via controlling tumour-associated macrophage phenotypes and is associated with breast cancer survival and treatment response

2021 ◽  
Author(s):  
Taewoo Kim ◽  
Jessica Johnston ◽  
Francisco J. C. Felipe ◽  
Stephen Hamby ◽  
Sonia Castillo-Lluva ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumour Growth ◽  
Molecular Mechanisms ◽  
Cancer Survival ◽  
Selective Reduction ◽  
Tumour Volume ◽  
Negative Regulator ◽  
Response To Chemotherapy

Molecular mechanisms that regulate tumour-associated macrophage (TAM) phenotype and function are incompletely understood. Here, we show that the pseudokinase TRIB1 is highly expressed by TAMs in breast cancer and that its expression correlates with response to chemotherapy and patient survival. We used immune-competent murine models of breast cancer to characterise the consequences of altered (reduced or elevated) myeloid Trib1 expression on tumour growth and composition of stromal immune cells. We found that both overexpression and knockout of myeloid Trib1 promote tumour growth, albeit through distinct molecular mechanisms. Myeloid Trib1 deficiency resulted in an early accelearation of tumour growth, paired with a selective reduction in perivascular macrophage numbers in vivo and enhanced oncogenic cytokine expression in vitro. In contrast, elevated levels of Trib1 in myeloid cells led to an increase in mammary tumour volume at late stages, together with a reduction of NOS2 expressing macrophages and an overall reduction of these cells in hypoxic tumour regions. In addition, we show that myeloid Trib1 is a previously unknown, negative regulator of the anti-tumour cytokine IL-15 and that increased expression of myeloid Trib1 leads to reduced IL-15 levels in mammary tumours, with a consequent reduction in the number of T-cells, that are key to anti-tumour immune responses. Together, these results define the different roles of TRIB1 in human breast cancer and provide a mechanistic understanding for the importance of myeloid TRIB1 expression levels in the development of this disease.

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