Triple negative breast cancer in Asia: An insider’s view

Wang, Chao; Kar, Shreya; Lai, Xianning; Cai, Wanpei; Arfuso, Frank; Sethi, Gautam; Lobie, Peter E.; Goh, Boon Cher; Lim, Lina H.K.; Hartman, Mikael; Chan, Ching Wan; Lee, Soo C.; Tan, S. G.; Kumar, Alan Prem

doi:10.1016/j.ctrv.2017.10.014

Cited by 147 publications

(112 citation statements)

References 97 publications

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“…We noted several metabolites as novel in our study, including N-acetyl-L-histidine, phosphatidylinositol (PIP), phosphatidylinositol (PI), and dehydroascorbic acid. These metabolic signatures could be sourced from the unique genetic, lifestyle, and other environmental factors, leading to the unique TNBC phenotype in Asian females, such as being diagnosed at a younger age of 40-50 and more aggressive disease behavior 16 . Therefore, these unique metabolic signatures could potentially be used to further investigate the intriguing mechanism of race-specific TNBC phenotypes and disease outcome.…”

Section: Discussionmentioning

confidence: 99%

Metabolomics-Based Discovery of Molecular Signatures for Triple Negative Breast Cancer in Asian Female Population

Zheng

Zhou

et al. 2020

Sci Rep

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Triple negative breast cancer (TNBC) is a devastating cancer disease characterized by its poor prognosis, distinct metastatic patterns, and aggressive biological behavior. Research indicates that the prevalence and presentation of TNBC varies among races, with Asian TNBC patients more commonly presenting with large invasive tumors, high node positivity, and high histologic grade. In this work, we applied ultra-high performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS)based metabolomics to discover metabolic signatures in Asian female TNBC patients. Serum samples from 31 TNBC patients and 31 healthy controls (CN) were involved in this study. A total of 2860 metabolic features were detected in the serum samples. Among them, 77 metabolites, whose levels were significantly different between TNBC with CN, were confirmed. Using multivariate statistical analysis, literature mining, metabolic network and pathway analysis, we performed an in-depth study of the metabolic alterations in the Asian TNBC population. In addition, we discovered a panel of metabolic signatures that are highly correlated with the 5-year survival rate of the TNBC patients. this metabolomic study provides a better understanding of the metabolic details of tnBc in the Asian population. Among women, breast cancer (BC) is the most common type of cancer and also the 2 nd leading cause of death worldwide 1. BC can be divided into several major subtypes based on conventional immunohistochemistry detection of hormone receptors, including human estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth receptor-2 (HER2). As a highly heterogeneous disease, patients with BC have various morphological spectrum, clinical presentation, and prognostic outcomes 2. Among the various subtypes, triple negative breast cancer (TNBC) uniquely lacks expression of all three hormone receptors and accounts for 15-20% of the BC cases. TNBC has attracted more attention compared with other BC subtypes as it is typically associated with high aggression, poor prognosis and a high risk of disease relapse within 5 years following diagnosis 3. Women with TNBC have a high frequency of metastasis to the lung, liver and brain, and survival is generally poor. Another troubling feature associated with the disease is the disparity of presentation and survival compared with other ethnicities 4-9. It is thus of great demand to study the molecular basis of TNBC in order to guide the development of promising drugs and therapies for treatment. Metabolomics is an emerging technology for health science research, representing a more recent addition to the suite of "omics" tools. In particular, mass spectrometry (MS)-based metabolomic analysis enables the most comprehensive measurement of metabolites in a given biological system. It is thus a powerful analytical tool to identify metabolic biomarkers associated with disease or abnormal phenotypes for clinical applications 4. Since metabolites are the end products of gene regulatory processes and prote...

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Section: Discussionmentioning

confidence: 99%

Metabolomics-Based Discovery of Molecular Signatures for Triple Negative Breast Cancer in Asian Female Population

Zheng

Zhou

et al. 2020

Sci Rep

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“…In this work, we tested the cytotoxic activity of Ilamycin C in TNBC cell lines (MDA-MB-231 and BT-549), non-TNBC cell line (MCF7), and normal breast epithelial cell line (MCF10A) . Doxorubicin and cisplatin are the traditional clinical chemotherapy drugs for TNBC [43]. Interestingly, compared with doxorubicin and cisplatin, the IC 50 values revealed that the cytotoxic activity of Ilamycin C is more specific to TNBC cells than non-TNBC MCF7 and nonmalignant MCF10A cells, implying Ilamycin C may play a selective inhibitory role in TNBC, implying Ilamycin C has potential to serve as a novel clinical chemotherapy drug for the treatment of TNBC.…”

Section: Discussionmentioning

confidence: 99%

Ilamycin C induces apoptosis and inhibits migration and invasion in triple-negative breast cancer by suppressing IL-6/STAT3 pathway

et al. 2019

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Background: Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer with poor prognosis, and its treatment remains a challenge due to few targeted medicines and high risk of relapse, metastasis, and drug resistance. Thus, more effective drugs and new regimens for the therapy of TNBC are urgently needed. Ilamycins are a kind of cyclic peptides and produced by Streptomyces atratus and Streptomyces islandicus with effective anti-tuberculosis activity. Ilamycin C is a novel compound isolated from the deep South China Seaderived Streptomyces atratus SCSIO ZH16 and exhibited a strong cytotoxic activity against several cancers including breast cancer cell line MCF7. However, the cytotoxic activity of Ilamycin C to TNBC cells and a detailed antitumor mechanism have not been reported. Methods: CCK-8 assays were used to examine cell viability and cytotoxic activity of Ilamycin C to TNBC, non-TNBC MCF7, and nonmalignant MCF10A cells. EdU assays and flow cytometry were performed to assess cell proliferation and cell apoptosis. Transwell migration and Matrigel invasion assays were utilized to assess the migratory and invading capacity of TNBC cells following the treatment of Ilamycin C. The expressions of proteins were detected by western blot. Results: In this study, we found that Ilamycin C has more preferential cytotoxicity in TNBC cells than non-TNBC MCF7 and nonmalignant MCF10A cells. Notably, our studies revealed the mechanism that Ilamycin C can induce Bax/Bcl-2-related caspase-dependent apoptosis and inhibit migration and invasion through MMP2/MMP9/vimentin/ fascin in TNBC by suppressing IL-6-induced STAT3 phosphorylation. Conclusions: This study provides the first evidence that Ilamycin C has significant implications for the potential as a novel IL-6/STAT3 inhibitor for TNBC treatment in the future.

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“…These studies illustrate the ability of genistein and daidzein to have estrogen mimicking activities and alter the expression of genes associated with cell communication, lipid metabolism, signal transduction, fatty acid synthesis, and cell growth (Guo et al, ; Satih et al, ). However, the overall risk factor for TNBC in Asia has been reported to be the same as in western countries (Wang et al, ).…”

Section: Breast Physiology and Cancermentioning

confidence: 99%

Phytoestrogens: The current state of research emphasizing breast pathophysiology

Senthilkumar

Fata

Kennelly

2018

Phytotherapy Research

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Phytoestrogens, a class of plant-derived compounds that are structural mimics of estrogen, can bind to estrogen receptors, acting as either agonists or antagonists. They have been implicated in estrogen-mediated physiology, which makes them interesting targets of study, especially for biomedical applications in woman's health. The 1998 Women's Health Initiative sparked considerable interest in natural alternatives to hormone replacement therapy, thereby triggering many additional studies on phytoestrogens. In this review, key advancements in dietary phytoestrogens are addressed, emphasizing their relation to breast pathophysiology. Recent developments such as clinical trials, precise bioassays for screening and selection of potential phytoestrogens, drug delivery systems to enhance bioavailability of therapeutically favorable phytoestrogens, regulatory guidelines on phytoestrogen-based supplements, and avenues that need further improvement are also discussed.

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Triple negative breast cancer in Asia: An insider’s view

Cited by 147 publications

References 97 publications

Metabolomics-Based Discovery of Molecular Signatures for Triple Negative Breast Cancer in Asian Female Population

Metabolomics-Based Discovery of Molecular Signatures for Triple Negative Breast Cancer in Asian Female Population

Ilamycin C induces apoptosis and inhibits migration and invasion in triple-negative breast cancer by suppressing IL-6/STAT3 pathway

Phytoestrogens: The current state of research emphasizing breast pathophysiology

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