Enhancing the therapeutic effect via elimination of hepatocellular carcinoma stem cells using Bmi1 siRNA delivered by cationic cisplatin nanocapsules

Publication date: Available online 26 May 2018Source: Nanomedicine: Nanotechnology, Biology and MedicineAuthor(s): Tan Yang, Yuyuan Chen, Pengxuan Zhao, Huiying Xue, Jia You, Bin Li, Yong Liu, Chuanchuan He, Xiaojuan Zhang, Lingling Fan, Robert J. Lee, Lei Li, Xiang Ma, Chuanrui Xu, Guangya XiangResistance of hepatocellular carcinoma (HCC) to systemic chemotherapy is partially due to presence of drug-resistant cancer stem cells. Bmi1 protein is essential for survival and proliferation of HCC cancer stem cells (CSCs). Here, we report that Bmi1 siRNA (Bmi1siR) loaded in cationic nanocapsules of cisplatin (NPC) eliminated stem cells in situ HCC in mice. NPC/Bmi1siR was fabricated via electrostatic complexation of Bmi1 siRNA to NPCs, which had cores composed of cisplatin and were coated with cationic lipids. In vivo, NPC/Bmi1siR showed higher anti-tumor activity in HCC bearing mice compared with cisplatin or NPC. Critically, both flow cytometry (FACS) analysis in vitro and histological examination in vivo revealed that side population or CD133+ HCC cells were dramatically decreased by NPC/Bmi1siR treatment, suggesting that HCC CSCs were eliminated. Altogether, our results suggest that drug resistance of HCC can be overcome by co-delivering Bmi1 siRNA with cisplatin in cationic nanocapsules.Graphical abstractAn illustration of intracellular trafficking of NPC/Bmi1siR nanocapsules. After injection, NPC/Bmi1siR nanocapsules escape from blood vessel and enter to the tumor. NPC/Bmi1si...
Source: Nanomedicine: Nanotechnology, Biology and Medicine - Category: Nanotechnology Source Type: research

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Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
Discussion MDSCs violently emerge in pathological conditions in an attempt to limit potentially harmful immune and inflammatory responses. Mechanisms supporting their expansion and survival are deeply investigated in cancer, in the perspective to reactivate specific antitumor responses and prevent their contribution to disease evolution. These findings will likely contribute to improve the targeting of MDSCs in anticancer immunotherapies, either alone or in combination with immune checkpoint inhibitors. New evidence indicates that the expansion of myeloid cell differentiation in pathology is subject to fine-tuning, as its...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Alessandro Poggi1*, Roberto Benelli2, Roberta Venè1, Delfina Costa1, Nicoletta Ferrari1, Francesca Tosetti1 and Maria Raffaella Zocchi3 1Molecular Oncology and Angiogenesis Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy 2Immunology Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy 3Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy It is well established that natural killer (NK) cells are involved in both innate and adaptive immunity. Indeed, they can recognize molecules induced at the cell surface by stress signals ...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Antonio Lucena-Cacace1, Masayuki Umeda1, Lola E. Navas2,3 and Amancio Carnero2,3* 1Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application, Kyoto University, Kyoto, Japan 2CIBERONC, ISCIII, Madrid, Spain 3Instituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocío (HUVR), CSIC, Universidad de Sevilla, Sevilla, Spain Glioma Cancer Stem-Like Cells (GSCs) are a small subset of CD133+ cells with self-renewal properties and capable of initiating new tumors contributing to Glioma progression, maintenance, hierarchy, and complexity. GSCs are highly res...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
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Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Conclusions: This meta-analysis demonstrated that CD44 overexpression might be an unfavorable prognostic factor for CRC patients and could be used to predict poor differentiation, lymph node metastasis and distant metastasis. Introduction Although therapies for colorectal cancer (CRC) has improved in recent years, colorectal cancer is still the third most common cause of cancer related death worldwide (1). Metastasis are observed in 25% of patients at initial diagnosis and approximately 50% of patients will develop metastasis (2). Presently, the outcome prediction and the therapy schedule determination of CRC patie...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
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Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
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Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
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Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
This study aimed to investigate whether combining anti-PD-L1 Atezolizumab with BEV may have a synergistic effect and enhance the efficacy of both treatments in cisplatin resistant epithelial ovarian cancer (CREOC). We retrospectively analyzed 124 epithelial ovarian cancer (EOC) patients from Gynecologic Oncology Department of Tianjin Cancer Hospital between January 2013 and June 2018, who all were diagnosed with cisplatin resistance due to progressing
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