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The MRI-Visible Nanocomposite Facilitates the Delivery and Tracking of siRNA Loaded DC Vaccine in the Breast Cancer Model
Dendritic cell (DC) vaccines have recently been developed for the treatment of various cancers but often do not function as well as expected, primarily due to the highly complex in vivo immune environment. This proof-of-principle study aimed to test the feasibility of modulating the in vivo behaviors of DC vaccines (DCVs) by introducing siRNA-laden magnetic resonance (MR) imaging nanovectors into cells, while providing visible information on their homing to lymph nodes. The N-alkyl-PEI2k-LAC/SPIO nanocomposites were prepared and characterized, showing favorable properties of siRNA transfection and MRI labeling efficiency i...
Source: Frontiers in Oncology - February 5, 2021 Category: Cancer & Oncology Source Type: research

RNA Nanotechnology-Mediated Cancer Immunotherapy
RNA molecules (e.g., siRNA, microRNA, and mRNA) have shown tremendous potential for immunomodulation and cancer immunotherapy. They can activate both innate and adaptive immune system responses by silencing or upregulating immune-relevant genes. In addition, mRNA-based vaccines have recently been actively pursued and tested in cancer patients, as a form of treatment. Meanwhile, various nanomaterials have been developed to enhance RNA delivery to the tumor and immune cells. In this review article, we summarize recent advances in the development of RNA-based therapeutics and their applications in cancer immunotherapy. We als...
Source: Theranostics - July 3, 2020 Category: Molecular Biology Authors: Yao-Xin Lin, Yi Wang, Sara Blake, Mian Yu, Lin Mei, Hao Wang, Jinjun Shi Tags: Review Source Type: research

IL-6 expression promoted by Poly(I:C) in cervical cancer cells regulates cytokine expression and recruitment of macrophages.
In this study, we investigated the roles of poly(I:C) in the cervical cancer. We analysed the cytokine transcription and secretion of cervical cancer cell lines and THP-1-derived macrophages after poly(I:C) treatment, respectively. These results revealed that IL-6 was significantly up-regulated, and this up-regulation was partly dose dependent. poly(I:C)-stimulated supernatant of cervical cancer cells promoted M1-type cytokine IL-1β and IL-6 expression of THP-1-derived macrophages, but inhibited the expression of M2-type cytokine, IL-10 and CCL22. The recruitment of THP-1-derived macrophages by poly(I:C)-stimulated cervic...
Source: J Cell Mol Med - January 13, 2020 Category: Molecular Biology Authors: Liu X, Meng L, Chen L, Liang Y, Wang B, Shao Q, Wang H, Yang X Tags: J Cell Mol Med Source Type: research

TEX19 promotes ovarian carcinoma progression and is a potential target for epitope vaccine immunotherapy
This study aimed to reveal the role of TEX19 in ovarian cancer (OC) and searched for potential candidate epitope peptides of TEX19 to facilitate clinical application.Main methodsTEX19 levels were evaluated by immunohistochemistry (IHC) in 98 human ovarian tissue samples. The correlation of TEX19 levels with patients' clinicopathological features was assessed. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting analysis were utilized to detect TEX19 levels in ovarian cell lines and TEX19-deficient cells. The level of TEX19 in OVCAR-3 and A2780 was knocked down by small interfering RNA (siRNA), an...
Source: Life Sciences - December 14, 2019 Category: Biology Source Type: research

Blockage of immune checkpoint molecules increases T cell priming potential of dendritic cell vaccine.
In this study, we silenced the expression of PD-L1 in DCs and PD-1 in T cells by siRNA-loaded chitosan-dextran sulfate nanoparticles (NPs) and evaluated the DC phenotypic and functional characteristics and T cells functions following tumor antigen recognition on DCs, ex vivo. Our results showed that synthesized NPs had good physicochemical characteristics (size of 77.5 nm and zeta potential of 14.3) that was associated with efficient cellular uptake and target gene silencing. Moreover, PD-L1 silencing was associated with stimulatory characteristics of DCs. On the other hand, presentation of tumor antigens by PD-L1 negative...
Source: Immunology - October 5, 2019 Category: Allergy & Immunology Authors: Hassannia H, Ghasemi Chaleshtari M, Atyabi F, Nosouhian M, Masjedi A, Hojjat-Farsangi M, Namdar A, Azizi G, Mohammadi H, Ghalamfarsa G, Sabz G, Hasanzadeh S, Yousefi M, Jadidi-Niaragh F Tags: Immunology Source Type: research

siRNA nanotherapeutics: a promising strategy for anti-HBV therapy
Chronic hepatitis B (CHB) is the most common cause of hepatocellular carcinoma (HCC) and liver cirrhosis worldwide. In spite of the numerous advances in the treatment of CHB, drugs and vaccines have failed because of many factors like complexity, resistance, toxicity, and heavy cost. New RNA interference (RNAi)-based technologies have developed innovative strategies to target Achilles' heel of the several hazardous diseases involving cancer, some genetic disease, autoimmune illnesses, and viral disorders particularly hepatitis B virus (HBV) infections. Naked siRNA delivery has serious challenges including failure to cross ...
Source: IET Nanobiotechnology - June 21, 2019 Category: Nanotechnology Source Type: research

Role of PGRMC1 in cell physiology of cervical cancer
In this study, we performed 2D-DIGE and MALDI-TOF/TOF MS to analyze differentially expressed proteins between HeLa and invasive HeLa-I5 cells..Key findingsAccording to our proteomics data, 68 differentially expressed proteins between the HeLa and HeLa-I5 cells were identified. One of these differentially expressed proteins, Progesterone receptor membrane component 1 (PGRMC1), was selected as a candidate for further studies. To correlate the role of PGRMC1 with cellular migration and cancer progression, small interfering RNA (siRNA) was used to knockdown the expression of PGRMC1. Similar function of PGRMC1 was also observed...
Source: Life Sciences - June 18, 2019 Category: Biology Source Type: research

Human CAR NK Cells: A New Non-viral Method Allowing High Efficient Transfection and Strong Tumor Cell Killing
In conclusion, the method of NK cell transfection described in our present study is highly efficient, does not require expensive dedicated structures necessary for viral transduction and avoids possible risks associated with the use of viral vectors. Importantly, it may be applied to NK cells or NK-92 cell line, greatly improving their anti-tumor activity and providing a new NK cell-based platform for new protocols of adoptive immuno-therapy of cancer. Ethics Statement The Ethical Committee of IRCCS Bambino Gesù Pediatric Hospital approved the study (825/2014). Author Contributions TI designed and performed res...
Source: Frontiers in Immunology - April 29, 2019 Category: Allergy & Immunology Source Type: research

Gene Therapy Leaves a Vicious Cycle
Reena Goswami1, Gayatri Subramanian2, Liliya Silayeva1, Isabelle Newkirk1, Deborah Doctor1, Karan Chawla2, Saurabh Chattopadhyay2, Dhyan Chandra3, Nageswararao Chilukuri1 and Venkaiah Betapudi1,4* 1Neuroscience Branch, Research Division, United States Army Medical Research Institute of Chemical Defense, Aberdeen, MD, United States 2Department of Medical Microbiology and Immunology, University of Toledo College of Medicine and Life Sciences, Toledo, OH, United States 3Roswell Park Comprehensive Cancer Center, Buffalo, NY, United States 4Department of Physiology and Biophysics, Case Western Reserve University, Clev...
Source: Frontiers in Oncology - April 23, 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

Immune-Modulation by the Human Respiratory Syncytial Virus: Focus on Dendritic Cells
This study is complemented by another report that found that hRSV infection induces significant expression of three miRNAs, namely hsa-miR-4448, hsa-miR-30a-5p, and hsa-miR-4634 in human DCs (104). Interestingly, this latter study also performed comparative analyses of miRNA profiles between DCs infected with hRSV and a related virus, namely the human metapneumovirus, and found that both viruses induced the expression of elevated levels of hsa-miR-4634. Elucidating the contribution of these miRNAs in DCs in response to hRSV remains to be determined. Dendritic Cell Phenotype and Migration Upon hRSV Infection in vivo Altho...
Source: Frontiers in Immunology - April 14, 2019 Category: Allergy & Immunology 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

SOCS and Herpesviruses, With Emphasis on Cytomegalovirus Retinitis
Christine I. Alston1,2 and Richard D. Dix1,2* 1Department of Biology, Viral Immunology Center, Georgia State University, Atlanta, GA, United States 2Department of Ophthalmology, Emory University School of Medicine, Atlanta, GA, United States Suppressor of cytokine signaling (SOCS) proteins provide selective negative feedback to prevent pathogeneses caused by overstimulation of the immune system. Of the eight known SOCS proteins, SOCS1 and SOCS3 are the best studied, and systemic deletion of either gene causes early lethality in mice. Many viruses, including herpesviruses such as herpes simplex virus and cytomega...
Source: Frontiers in Immunology - April 10, 2019 Category: Allergy & Immunology Source Type: research

Cancers, Vol. 11, Pages 176: Releasing the Immune System Brakes Using siRNAs Enhances Cancer Immunotherapy
d Therapeutic dendritic cell (DC) cancer vaccines rely on the immune system to eradicate tumour cells. Although tumour antigen-specific T cell responses have been observed in most studies, clinical responses are fairly low, arguing for the need to improve the design of DC-based vaccines. The incorporation of small interfering RNAs (siRNAs) against immunosuppressive factors in the manufacturing process of DCs can turn the vaccine into potent immune stimulators. Additionally, siRNA modification of ex vivo-expanded T cells for adoptive immunotherapy enhanced their killing potency. Most of the siRNA-targeted immune inhibit...
Source: Cancers - February 3, 2019 Category: Cancer & Oncology Authors: Mouldy Sioud Tags: Review Source Type: research

Cancers, Vol. 11, Pages 108: Cancer Immunotherapy: Silencing Intracellular Negative Immune Regulators of Dendritic Cells
eng-Chi Yen Dendritic cells (DCs) are capable of activating adaptive immune responses, or inducing immune suppression or tolerance. In the tumor microenvironment, the function of DCs is polarized into immune suppression that attenuates the effect of T cells, promoting differentiation of regulatory T cells and supporting tumor progression. Therefore, blocking negative immune regulators in DCs is considered a strategy of cancer immunotherapy. Antibodies can target molecules on the cell surface, but not intracellular molecules of DCs. The delivery of short-hairpin RNAs (shRNA) and small-interfering RNAs (siRNA) should be ...
Source: Cancers - January 17, 2019 Category: Cancer & Oncology Authors: Yao-Hua Liu I-Jeng Yeh Ming-Derg Lai Kuan-Ting Liu Po-Lin Kuo Meng-Chi Yen Tags: Review Source Type: research

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