scholarly journals Advances in Molecular and Immunohistochemical Detection of Prognostic and Therapeutic Markers in Breast Cancer

2020 ◽  
Author(s):  
Rodrigo Vismari de Oliveira
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
Human Cancer ◽  
Clinical Status ◽  
New Drugs ◽  
Cancer Prognosis ◽  
Stem Cell Markers ◽  
Cell Markers ◽  
Her 2 ◽  
Clinical Correlations

In the last two decades, new discoveries concerning on breast cancer have contributed to important changes on its classification, from purely morphologic to molecular embased, to establish better correlation with clinicopathologic features. The classification in molecular subtypes, based on hormonal receptor and HER-2 status, have been remarkable not only for its more accurated clinical correlations, but also for its easy applicability in diagnostic routine, better replication of tumor microenvironment through the selection of paraffinized tumor amounts and cost-effectiveness of the detection method, the immunohistochemistry. Hence, this classification may predict the breast cancer prognosis and became an important target for therapy with hormonal and HER-2 antagonist drugs. Other study models, like cancer-stem cell hypothesis and immunological aspects of human cancer, have brought new emerging ideas regarding on molecular pathways and accurated prognostic preditions. Putative stem-cell markers and PD-1/PDL-1, have highlighted among several emerging molecular markers because of the bad cancer prognosis determinated by stem-cell markers expression and for emerging new drugs with selective action to PD-1/PDL-1, with promising results. The therapy of breast cancer have became diverse, target directed and personalized, in order to take in consideration the clinicopathologic cancer aspects, molecular tumor profile and clinical status of the patient.

A small molecule LN435a targeting TGFβR1 exerts promising antitumor effects on breast cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15069-e15069
Author(s):  
Yuzhu Zhang ◽  
Huachao Li ◽  
Hongyan Zhang ◽  
Xiaoyuan Liu ◽  
Tianyu Luo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
Anticancer Activity ◽  
Multiple Drug Resistance ◽  
Cancer Drug ◽  
Her2 Status ◽  
Stem Cell Markers ◽  
Antitumor Effects ◽  
Cell Markers ◽  
Anti Cancer

e15069 Background: Breast cancer has overtaken lung cancer as the most diagnosed cancer. Despite conventional treatment, metastases occur in 20-30% of patients, resulting in death. This study aims to screen of effective drugs by metastatic patient-derived organoid and the potential molecular mechanism. Methods: Breast Cancer patient-derived organoid (PDO) model was established from the patient who have multiple drug resistance, multiple visceral and contralateral breast metastases. The organoid morphologies was tested by hematoxylin-eosin (HE) staining and immunohistochemistry (IHC). Then, pharmacological activity assay of 2370 natural product monomer (from Selleck) was performed with organoids. we modified the structure of harmine(HM) and screened the best active drugs. Cell proliferation assay and wound healing assay were used to detect LN435a anticancer activity in vitro. Orthotopic, Metastatic Xenograft and Patient-Derived tumor Xenograft(PDX) model of Breast Cancer were used to detect LN435a anticancer activity in vivo. In order to explore the anti-cancer target of LN435a, we used RNA transcriptome and proteomics sequencing. To further validate anti-cancer targets,TGFβ receptor 1 (TGFβR1), we used real-time quantitative qPCR, western blot, lentiviral packing and biolayer interferometry assay. To investigate whether LN435a inhabition of EMT and stem cell markers, we performed flow cytometry, immunohistochemistry and fluorescence. Results: We observe that organoid morphologies typically matched the histopathology, hormone receptor status, and HER2 status of the original tumor. In the first anti-cancer drug screening, HM showes the best effect on PDO. Because HM contains β-carbine alkaloids as the structural units, we designe a series of active drugs based on this and did anticancer screening. We find LN435a as one of the lead compounds exerting anti-metastatic activity in the nanomolar range in PDO and breast cancer cells. Proteomic and biochemical studies identify TGFβR1 as the direct target of LN435a. And then it inhibits EMT and stem cell markers. In parallel, loss of TGFβR1 or pharmacological inhibition of TGFβR1 by LN435a reduces breast cancer extravasation into the lung in an experimental metastasis mouse model, which reveals an essential role of TGFβR1 in breast cancer progression. Conclusions: Altogether, LN435a is a novel inhibitor of promising anti-tumor effects on breast cancer that works by blocking TGFβ signaling pathways.

scholarly journals Multiple Lineages of Human Breast Cancer Stem/Progenitor Cells Identified by Profiling with Stem Cell Markers

PLoS ONE ◽  
2009 ◽  
Vol 4 (12) ◽  
pp. e8377 ◽  
Author(s):  
Wendy W. Hwang-Verslues ◽  
Wen-Hung Kuo ◽  
Po-Hao Chang ◽  
Chi-Chun Pan ◽  
Hsing-Hui Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
Progenitor Cells ◽  
Human Breast Cancer ◽  
Stem Cell Markers ◽  
Human Breast ◽  
Cell Markers

Cancer stem cell markers are associated with adverse biomarker profiles and molecular subtypes of breast cancer

2012 ◽  
Vol 136 (2) ◽  
pp. 407-417 ◽  
Author(s):  
Julia Y. S. Tsang ◽  
Yu-Hua Huang ◽  
Ming-Hua Luo ◽  
Yun-Bi Ni ◽  
Siu-Ki Chan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
Cancer Stem Cell ◽  
Molecular Subtypes ◽  
Stem Cell Markers ◽  
Cell Markers ◽  
Cancer Stem Cell Markers

scholarly journals Breast cancer cells expressing stem cell markers CD44+ CD24lo are eliminated by Numb-1 peptide-activated T cells

2008 ◽  
Vol 58 (8) ◽  
pp. 1185-1194 ◽  
Author(s):  
Takashi Mine ◽  
Satoko Matsueda ◽  
Yufeng Li ◽  
Hiroshi Tokumitsu ◽  
Hui Gao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Stem Cell ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Stem Cell Markers ◽  
Activated T Cells ◽  
Cell Markers
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