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Recombinant Dual-target MDM2/MDMX Inhibitor Reverses Doxorubicin Resistance through Activation of the TAB1/TAK1/p38 MAPK Pathway in Wild-type p53 Multidrug-resistant Breast Cancer Cells
Chemotherapy resistance represents a major obstacle for the treatment of patients with breast cancer (BC) and greatly restricts the therapeutic effect of the first-line chemotherapeutic agent doxorubicin (DOX). The present study aimed to investigate the feasibility of the recombinant dual-target murine double minute 2 (MDM2) and murine double minute X (MDMX) inhibitor in reversing the DOX resistance of BC. Both DOX-resistant human breast carcinoma cell lines exhibited a multidrug resistance (MDR) phenotype. The ability of the dual-target MDM2/MDMX inhibitor in reversing doxorubicin resistance was subsequently verified, (9....
Source: Journal of Cancer - July 2, 2020 Category: Cancer & Oncology Authors: Yangwei Fan, Ke Ma, Jiayu Jing, Chuying Wang, Yuan Hu, Yu Shi, Enxiao Li, Qianqian Geng Tags: Research Paper Source Type: research

Inhibition of SMYD2 Sensitized Cisplatin to Resistant Cells in NSCLC Through Activating p53 Pathway
In conclusion, the present study elucidated that the activity of SMYD2 in NSCLC may affect the cell sensitivity to chemotherapeutic agents, especially to CDDP. The elevated SMYD2 mediated CDDP resistance and malignant phenotype in NSCLC, indicating that SMYD2 may be a useful biomarker of CDDP resistance in NSCLC. Inhibition of SMYD2 contributes to the methylation-related activation of p53 and thus results in cell apoptosis. Furthermore, combination treatment with CDDP and an SMYD2 inhibitor had a synergistically antitumor effects in a xenograft model in vivo. Given that SMYD2 has reversible effects and is a targetable prot...
Source: Frontiers in Oncology - April 25, 2019 Category: Cancer & Oncology Source Type: research

Myeloid Derived Suppressor Cells Interactions With Natural Killer Cells and Pro-angiogenic Activities: Roles in Tumor Progression
Conclusions MDSC are major players in the immunosuppressive scenario in cancer, thanks to their phenotype heterogeneity and critical interaction with several innate immune cells, thus representing a crucial target in oncology. Here we reviewed the interactions of MDSCs with NK cells. The contribution of key cytokines, chemokines and mediators active in this process have been discussed. We also described the contribution of MDSC on angiogenesis directly or indirectly through interactions with NK and immunosuppressive activities. A parallel of the cancer associated to the decidual counterpart of these cells is discussed, a...
Source: Frontiers in Immunology - April 17, 2019 Category: Allergy & Immunology Source Type: research

Sanguinarine Induces Apoptosis Pathway in Multiple Myeloma Cell Lines via Inhibition of the JaK2/STAT3 Signaling
In this study, we aimed to investigate the potential anti-proliferative and pro-apoptotic activities of SNG in a panel of MM cell lines (U266, IM9, MM1S, and RPMI-8226). SNG treatment of MM cells resulted in a dose-dependent decrease in cell viability through mitochondrial membrane potential loss and activation of caspase 3, 9, and cleavage of PARP. Pre-treatment of MM cells with a universal caspase inhibitor, Z-VAD-FMK, prevented SNG mediated loss of cell viability, apoptosis, and caspase activation, confirming that SNG-mediated apoptosis is caspase-dependent. The SNG-mediated apoptosis appears to be resulted from suppres...
Source: Frontiers in Oncology - April 16, 2019 Category: Cancer & Oncology Source Type: research

High Expression of DEPDC1 Promotes Malignant Phenotypes of Breast Cancer Cells and Predicts Poor Prognosis in Patients With Breast Cancer
In this study, the immunohistochemistry results demonstrated that DEPDC1 was high-expressed in breast cancer tissues compared with the paired adjacent normal breast tissues, and its tendency at protein level was consistent with mRNA level from TCGA data. Moreover, DEPDC1 mRNA level revealed the strongest association with poor prognosis and development in breast cancer. In vitro assays showed that DEPDC1 overexpression resulted in significant promotion of proliferation by regulating cell cycle in MCF-7 cells, whilst an opposite effect was found in the MDA-MB-231 cells with DEPDC1 deletion. Notably, further investigation ind...
Source: Frontiers in Oncology - April 11, 2019 Category: Cancer & Oncology Source Type: research

Hepatoma-Derived Growth Factor and DDX5 Promote Carcinogenesis and Progression of Endometrial Cancer by Activating β-Catenin
Conclusion: Our results provide novel evidence that HDGF interacts with DDX5 and promotes the progression of EC through the induction of β-catenin. Introduction Endometrial cancer (EC) comprises the most common malignancy involving the female genital tract and the fourth most common malignancy in women after breast, lung, and colorectal cancers (1). In 2012, approximately 320,000 new cases of EC were diagnosed worldwide and the incidence is increasing (2). Currently, endometrial carcinogenesis is thought to be a multi-step process involving the coordinated interaction of hormonal regulation, gene mutation, ad...
Source: Frontiers in Oncology - April 10, 2019 Category: Cancer & Oncology Source Type: research

Polyamidoamine dendrimers-based nanomedicine for combination therapy with siRNA and chemotherapeutics to overcome multidrug resistance.
Abstract Multidrug resistance (MDR) significantly decreases the therapeutic efficiency of anti-cancer drugs. Its reversal could serve as a potential method to restore the chemotherapeutic efficiency. Downregulation of MDR-related proteins with a small interfering RNA (siRNA) is a promising way to reverse the MDR effect. Additionally, delivery of small molecule therapeutics simultaneously with siRNA can enhance the efficiency of chemotherapy by dual action in MDR cell lines. Here, we conjugated the dendrimer, generation 4 polyamidoamine (G4 PAMAM), with a polyethylene glycol (PEG)-phospholipid copolymer. The amphip...
Source: European Journal of Pharmaceutics and Biopharmaceutics - January 8, 2019 Category: Drugs & Pharmacology Authors: Pan J, Palmerston Mendes L, Yao M, Filipczak N, Garai S, Thakur GA, Sarisozen C, Torchilin VP Tags: Eur J Pharm Biopharm Source Type: research

Focal Adhesion Kinase and Wnt Signaling Regulate Human Ductal Carcinoma In Situ Stem Cell Activity and Response to Radiotherapy
Abstract Cancer stem cells (CSCs) can avoid or efficiently repair DNA damage from radio and chemotherapy, which suggests they play a role in disease recurrence. Twenty percentage of patients treated with surgery and radiotherapy for ductal carcinoma in situ (DCIS) of the breast recur and our previous data show that high grade DCIS have increased numbers of CSCs. Here, we investigate the role of focal adhesion kinase (FAK) and Wnt pathways in DCIS stem cells and their capacity to survive irradiation. Using DCIS cell lines and patient samples, we demonstrate that CSC‐enriched populations are relatively radioresistant and p...
Source: Stem Cells - January 22, 2015 Category: Stem Cells Authors: Kathryn E. Williams, Nigel J. Bundred, Göran Landberg, Robert B. Clarke, Gillian Farnie Tags: Cancer Stem Cells Source Type: research

Abstract 1131: Snail- and ERK2-dependent signaling enhances breast cancer cell resistance to hydroxytamoxifen
Snail transcription factor and MAPK/ERK signaling regulate EMT and chemotherapy resistance in various tumor models by binding to target promoters (i.e., E-cadherin, maspin, ER-α). ERK1 is expressed during embryogenesis and in non-metastatic cells; ERK2 is implicated during vasculogenesis and promotes stem cell phenotype in triple negative breast cancer. Nuclear-localized ERK is associated with more active and potentially metastatic breast and ovarian carcinoma cells; cytoplasmic-localized ERK is a good prognostic factor. The role that Snail plays during the transition from cytoplasmic ERK1 to nuclear ERK2 has not been inv...
Source: Cancer Research - September 30, 2014 Category: Cancer & Oncology Authors: Smith, B. N., Nagappan, P., Taliaferro-Smith, L., Mezencev, R., Yates, C., Hinton, C., Odero-Marah, V. Tags: Tumor Biology Source Type: research

Focal adhesion kinase and wnt signalling regulates human ductal carcinoma in situ stem cell activity and response to radiotherapy
Abstract Cancer stem cells (CSCs) can avoid or efficiently repair DNA damage from radio and chemotherapy, which suggests they play a role in disease recurrence. 20% of patients treated with surgery and radiotherapy for ductal carcinoma in Situ (DCIS) of the breast recur and our previous data shows that high grade DCIS have increased numbers of CSCs. Here, we investigate the role of Focal Adhesion Kinase (FAK) and Wnt pathways in DCIS stem cells and their capacity to survive irradiation. Using DCIS cell lines and patient samples we demonstrate that CSC‐enriched populations are relatively radioresistant and possess high FA...
Source: Stem Cells - September 3, 2014 Category: Stem Cells Authors: Kathryn E Williams, Nigel J Bundred, Göran Landberg, Robert B Clarke, Gillian Farnie Tags: Original Research Source Type: research

EIF5A2 is a novel chemoresistance gene in breast cancer.
CONCLUSION: This study shows that eIF-5A2 plays an important role in doxorubicin chemoresistance in breast cancer cells. PMID: 24638963 [PubMed - as supplied by publisher]
Source: Breast Cancer - March 18, 2014 Category: Cancer & Oncology Authors: Liu Y, Du F, Chen W, Yao M, Lv K, Fu P Tags: Breast Cancer Source Type: research

CD44/cellular prion protein interact in multidrug resistant breast cancer cells and correlate with responses to neoadjuvant chemotherapy in breast cancer patients
Abstract Multidrug resistance (MDR) is one of the most important factors leading to chemotherapeutic failure in patients with breast cancer. The invasive/metastatic ability of MDR cells is strengthened compared with their parental cells. However, the mechanisms underlying MDR have not been fully elucidated. We found that CD44 and the cellular prion protein (PrPc) were both overexpressed in MDR cells (MCF7/Adr and H69AR). Subsequently, we chose the human breast cancer cell line MCF7/Adr, which is resistant to adriamycin, for further research. We discovered that PrPc physically and functionally interacted with CD44. The knoc...
Source: Molecular Carcinogenesis - May 16, 2013 Category: Molecular Biology Authors: Yuanyuan Cheng, Lili Tao, Jiawen Xu, Qingquan Li, Juan Yu, Yiting Jin, Qi Chen, Zude Xu, Qiang Zou, Xiuping Liu Tags: Research Article Source Type: research