scholarly journals Toll-like Receptor 9 in breast carcinoma is a good prognostic marker in patients treated with neoadjuvant chemotherapy

2020 ◽  
Author(s):  
Aradhana Singh ◽  
Arghya Bandyopadhyay ◽  
Narendranath Mukherjee ◽  
Anupam Basu
Keyword(s):  
Breast Cancer ◽  
Breast Carcinoma ◽  
Neoadjuvant Chemotherapy ◽  
Cancer Cells ◽  
Prognostic Marker ◽  
Immune Surveillance ◽  
Breast Cancer Patients ◽  
Tlr9 Expression ◽  
Kaplan Meier ◽  
Prognostic Importance

AbstractPurposeTLR9 is the sensor of fragmented nucleic acid signature as a part of innate immune surveillance. TLR9 can recognize the DNA fragments released from the chemotherapy-treated cancer cells in tumour tissue and induce an inflammatory response.The aim of this was toinvestigate the prognostic importance and survivability benefit of TLR9 expression in breast cancer patients treated with neoadjuvant chemotherapy.MethodsExpression of TLR9 in breast carcinoma samples was studied in two patient cohorts, with neoadjuvant chemotherapy (NACT), and without NACT, by immunohistochemistry. Expression of TLR9 was analysed in relation to prognosis, overall survivability as well as risk factor analysis for neoadjuvant chemotherapy treatment using web-tools like SurvExpress and K-M Plotter.ResultsTLR9 was expressed in malignant epithelial cancer cells as well as in adjacent stromal cells. TLR9 in malignant epithelial cells was significantly high in patients treated with neoadjuvant chemotherapy compared to the patients without neoadjuvant chemotherapy. The prognostic and survival analysis by SurvExpress and Kaplan-Meier plotter demonstrated that high TLR9 expression is related to better overall survival in patients treated with NACT.ConclusionsThus, we are showing for the first time that TLR9 is good prognostic marker in breast cancer treated with neoadjuvant chemotherapy and can be used for the selection of the neo-adjuvant regime.

Targeting PKM2 promotes chemosensitivity of breast cancer cells in vitro and in vivo

2021 ◽  
pp. 1-10
Author(s):  
Yu Wang ◽  
Han Zhao ◽  
Ping Zhao ◽  
Xingang Wang
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Poor Prognosis ◽  
Breast Cancer Cells ◽  
Breast Cancer Patients ◽  
Cancer Tissues

BACKGROUND: Pyruvate kinase M2 (PKM2) was overexpressed in many cancers, and high PKM2 expression was related with poor prognosis and chemoresistance. OBJECTIVE: We investigated the expression of PKM2 in breast cancer and analyzed the relation of PKM2 expression with chemotherapy resistance to the neoadjuvant chemotherapy (NAC). We also investigated whether PKM2 could reverse chemoresistance in breast cancer cells in vitro and in vivo. METHODS: Immunohistochemistry (IHC) was performed in 130 surgical resected breast cancer tissues. 78 core needle biopsies were collected from breast cancer patients before neoadjuvant chemotherapy. The relation of PKM2 expression and multi-drug resistance to NAC was compared. The effect of PKM2 silencing or overexpression on Doxorubicin (DOX) sensitivity in the MCF-7 cells in vitro and in vivo was compared. RESULTS: PKM2 was intensively expressed in breast cancer tissues compared to adjacent normal tissues. In addition, high expression of PKM2 was associated with poor prognosis in breast cancer patients. The NAC patients with high PKM2 expression had short survival. PKM2 was an independent prognostic predictor for surgical resected breast cancer and NAC patients. High PKM2 expression was correlated with neoadjuvant treatment resistance. High PKM2 expression significantly distinguished chemoresistant patients from chemosensitive patients. In vitro and in vivo knockdown of PKM2 expression decreases the resistance to DOX in breast cancer cells in vitro and tumors in vivo. CONCLUSION: PKM2 expression was associated with chemoresistance of breast cancers, and could be used to predict the chemosensitivity. Furthermore, targeting PKM2 could reverse chemoresistance, which provides an effective treatment methods for patients with breast cancer.

scholarly journals MASKING ANTI-PHAGOCYTIC SIGNAL OF TUMOR BY PRO-PHAGOCYTIC SIGNAL-A KEY TO IMMUREMENT OF CANCER CELL

2016 ◽  
Vol 8 (9) ◽  
pp. 323
Author(s):  
Madheswaran Suresh ◽  
Malarvizhi Gurusamy ◽  
Natarajan Sudhakar
Keyword(s):  
Breast Cancer ◽  
Immune System ◽  
Breast Carcinoma ◽  
Cell Surface ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Immune Surveillance ◽  
Phagocytic Cell ◽  
Surveillance Mechanism

<p>Immune surveillance is a mechanism where cells and tissues are watched constantly by ever alerted immune system. Most incipient cancer cells are recognized and eliminated by the immune surveillance mechanism, but still tumors have the ability to evade immune surveillance and immunological killing. One greater arm that tumor use to evade immune surveillance, is by expressing anti-phagocytic signal (CD47). Here we present a provocative hypothesis where cancer cells are removed alive by phagocytic cell (DC). That in turn will elicit effective and higher immunogenic condition. All this could be possible by addition pro-phagocytic signal (PtdSer) over cancer cell surface (Breast Cancer), that mask the presence of anti-phagocytic signal (CD47). In other words, adding eat me signal (PtdSer) over the breast cancer cell surface that mask the presence of don’t eat me signal or anti-phagocytic signal present in breast cancer cell surface. This could be possible by using bi-specific antibody, conjugated to PEG-modified liposomes, which carry (PtdSer) pro-phagocytic signal (or) eat me signal, which target both CD47 and EGFRVIII on breast carcinoma. The simultaneous masking of anti-phagocytic signal, and adding of pro–phagocytic signal over cancer cell, will enhance the phagocytic clearance of live tumor cell and elicit immunological killing.</p>

scholarly journals SETD3 acts as a prognostic marker in breast cancer patients and modulates the viability and invasion of breast cancer cells

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Nourhan Hassan ◽  
Niklas Rutsch ◽  
Balázs Győrffy ◽  
Nancy Adriana Espinoza-Sánchez ◽  
Martin Götte
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Prognostic Marker ◽  
Breast Cancer Cells ◽  
Breast Cancer Patients

scholarly journals Initial Identification of UDP-Glucose Dehydrogenase as a Prognostic Marker in Breast Cancer Patients, Which Facilitates Epirubicin Resistance and Regulates Hyaluronan Synthesis in MDA-MB-231 Cells

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 246
Author(s):  
Daiana L. Vitale ◽  
Ilaria Caon ◽  
Arianna Parnigoni ◽  
Ina Sevic ◽  
Fiorella M. Spinelli ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Prognostic Marker ◽  
Glucose Dehydrogenase ◽  
Breast Cancer Patients ◽  
Kaplan Meier ◽  
Initial Identification ◽  
Prognosis Marker ◽  
Kaplan Meier Plotter ◽  
Worse Prognosis

UDP-glucose-dehydrogenase (UGDH) synthesizes UDP-glucuronic acid. It is involved in epirubicin detoxification and hyaluronan synthesis. This work aimed to evaluate the effect of UGDH knockdown on epirubicin response and hyaluronan metabolism in MDA-MB-231 breast cancer cells. Additionally, the aim was to determine UGDH as a possible prognosis marker in breast cancer. We studied UGDH expression in tumors and adjacent tissue from breast cancer patients. The prognostic value of UGDH was studied using a public Kaplan–Meier plotter. MDA-MB-231 cells were knocked-down for UGDH and treated with epirubicin. Epirubicin-accumulation and apoptosis were analyzed by flow cytometry. Hyaluronan-coated matrix and metabolism were determined. Autophagic-LC3-II was studied by Western blot and confocal microscopy. Epirubicin accumulation increased and apoptosis decreased during UGDH knockdown. Hyaluronan-coated matrix increased and a positive modulation of autophagy was detected. Higher levels of UGDH were correlated with worse prognosis in triple-negative breast cancer patients that received chemotherapy. High expression of UGDH was found in tumoral tissue from HER2--patients. However, UGDH knockdown contributes to epirubicin resistance, which might be associated with increases in the expression, deposition and catabolism of hyaluronan. The results obtained allowed us to propose UGDH as a new prognostic marker in breast cancer, positively associated with development of epirubicin resistance and modulation of extracellular matrix.

scholarly journals Biochemical Background in Mitochondria Affects 2HG Production by IDH2 and ADHFE1 in Breast Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1709
Author(s):  
Jitka Špačková ◽  
Klára Gotvaldová ◽  
Aleš Dvořák ◽  
Alexandra Urbančoková ◽  
Kateřina Pospíšilová ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Carcinoma ◽  
Cancer Cells ◽  
Cancer Biology ◽  
Breast Cancer Cells ◽  
Breast Cancer Patients ◽  
Wild Type ◽  
Isocitrate Dehydrogenase 2 ◽  
Enzyme Molecules ◽  
Analytical Approaches

Mitochondrial production of 2-hydroxyglutarate (2HG) can be catalyzed by wild-type isocitrate dehydrogenase 2 (IDH2) and alcohol dehydrogenase, iron-containing 1 (ADHFE1). We investigated whether biochemical background and substrate concentration in breast cancer cells promote 2HG production. To estimate its role in 2HG production, we quantified 2HG levels and its enantiomers in breast cancer cells using analytical approaches for metabolomics. By manipulation of mitochondrial substrate fluxes using genetic and pharmacological approaches, we demonstrated the existence of active competition between 2HG producing enzymes, i.e., IDH2 and ADHFE1. Moreover, we showed that distinct fractions of IDH2 enzyme molecules operate in distinct oxido-reductive modes, providing NADPH and producing 2HG simultaneously. We have also detected 2HG release in the urine of breast cancer patients undergoing adjuvant therapy and detected a correlation with stages of breast carcinoma development. In summary, we provide a background for vital mitochondrial production of 2HG in breast cancer cells with outcomes towards cancer biology and possible future diagnosis of breast carcinoma.

Persistence of AKT1 low quiescent cancer cells after neoadjuvant chemotherapy in triple negative breast cancer patients.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 11579-11579
Author(s):  
Sheheryar Kairas Kabraji ◽  
Xavier Sole ◽  
Ying Huang ◽  
Clyde Bango ◽  
Michaela Bowden ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Cancer Cells ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Immunofluorescence Microscopy ◽  
Chemotherapy Resistance ◽  
Breast Cancer Patients ◽  
Primary Tumors ◽  
Quantitative Immunofluorescence

11579 Background: The mechanisms that allow triple negative breast cancer (TNBC) tumors to survive neoadjuvant chemotherapy (NACT) are incompletely understood. Evidence suggests that proliferative heterogeneity may contribute to primary chemotherapy resistance in patients with localized triple negative breast cancer. However, the detailed characterization of a drug-resistant cancer cell state in residual TNBC tissue after NACT has remained elusive. AKT1lowquiescent cancer cells (QCCs) are a quiescent, epigenetically plastic, and chemotherapy resistant subpopulation initially identified in experimental cancer models. Here, we asked whether AKT1low QCCs actually exist in primary tumors from patients with TNBC and persist after treatment with NACT. Methods: We identified QCCs in primary and metastatic human breast tumors using automated, quantitative, immunofluorescence microscopy coupled with computational and statistical analysis. We obtained pre-treatment biopsy, post-treatment mastectomy, and metastatic specimens from a retrospective cohort of TNBC patients treated with neoadjuvant chemotherapy at Massachusetts General Hospital (n = 25). Using automated quantitative immunofluorescence microscopy, QCCs were identified as AKTlow / H3K9me2low / HES1high cancer cells using prespecified immunofluorescence intensity thresholds. QCCs were represented as 2D and 3D digital tumor maps and QCC percentage (QCC-P) and QCC cluster index (QCC-CI) were determined for each sample. Results: We found that QCCs exist as non-random and heterogeneously distributed clusters within primary tumors. In addition, these QCC clusters are enriched after treatment with multi-agent, multi-cycle, neoadjuvant chemotherapy in both residual primary tumors as well as nodal and distant metastases in patients with triple negative breast cancer. Conclusions: Together, these data qualify QCCs as a non-genetic mechanism of chemotherapy resistance in triple negative breast cancer patients that warrants further study.

scholarly journals Ki-67 as a controversial predictive and prognostic marker in breast cancer patients treated with neoadjuvant chemotherapy

2017 ◽  
Vol 12 (1) ◽  
Author(s):  
Balázs Ács ◽  
Veronika Zámbó ◽  
Laura Vízkeleti ◽  
A. Marcell Szász ◽  
Lilla Madaras ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Cancer Patients ◽  
Prognostic Marker ◽  
Breast Cancer Patients ◽  
Ki 67

scholarly journals FoxO3a as a Positive Prognostic Marker and a Therapeutic Target in Tamoxifen-Resistant Breast Cancer

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1858 ◽  
Author(s):  
Michele Pellegrino ◽  
Pietro Rizza ◽  
Ada Donà ◽  
Alessandra Nigro ◽  
Elena Ricci ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Endocrine Resistance ◽  
Breast Cancer Patients ◽  
Proteomics Data ◽  
Luminal A ◽  
Kaplan Meier ◽  
Tamoxifen Resistant

Background: Resistance to endocrine treatments is a major clinical challenge in the management of estrogen receptor positive breast cancers. Although multiple mechanisms leading to endocrine resistance have been proposed, the poor outcome of this subgroup of patients demands additional studies. Methods: FoxO3a involvement in the acquisition and reversion of tamoxifen resistance was assessed in vitro in three parental ER+ breast cancer cells, MCF-7, T47D and ZR-75-1, in the deriving Tamoxifen resistant models (TamR) and in Tet-inducible TamR/FoxO3a stable cell lines, by growth curves, PLA, siRNA, RT-PCR, Western blot, Immunofluorescence, Transmission Electron Microscopy, TUNEL, cell cycle, proteomics analyses and animal models. FoxO3a clinical relevance was validated in silico by Kaplan–Meier survival curves. Results: Here, we show that tamoxifen resistant breast cancer cells (TamR) express low FoxO3a levels. The hyperactive growth factors signaling, characterizing these cells, leads to FoxO3a hyper-phosphorylation and subsequent proteasomal degradation. FoxO3a re-expression by using TamR tetracycline inducible cells or by treating TamR with the anticonvulsant lamotrigine (LTG), restored the sensitivity to the antiestrogen and strongly reduced tumor mass in TamR-derived mouse xenografts. Proteomics data unveiled novel potential mediators of FoxO3a anti-proliferative and pro-apoptotic activity, while the Kaplan–Meier analysis showed that FoxO3a is predictive of a positive response to tamoxifen therapy in Luminal A breast cancer patients. Conclusions: Altogether, our data indicate that FoxO3a is a key target to be exploited in endocrine-resistant tumors. In this context, LTG, being able to induce FoxO3a, might represent a valid candidate in combination therapy to prevent resistance to tamoxifen in patients at risk.

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