scholarly journals RNA Hydrogel Combined with MnO2 Nanoparticles as a Nano-Vaccine to Treat Triple Negative Breast Cancer

2021 ◽  
Vol 9 ◽  
Author(s):  
Weicai Wang ◽  
Xiaofan Liu ◽  
Lairong Ding ◽  
Hyung Jong Jin ◽  
Xuemei Li
Keyword(s):  
Tumor Metastasis ◽  
Human Cancer ◽  
Tumor Hypoxia ◽  
Cancer Recurrence ◽  
Cancer Therapies ◽  
Mno2 Nanoparticles ◽  
Therapeutic Molecules ◽  
Chlorine E6 ◽  
Good Biocompatibility ◽  
Low Cytotoxicity

Hypoxia is not only the reason of tumor metastasis but also enhances the spread of cancer cells from the original tumor site, which results in cancer recurrence. Herein, we developed a self-assembled RNA hydrogel that efficiently delivered synergistic DNA CpG and short hairpin RNA (shRNA) adjuvants, as well as MnO2 loaded-photodynamic agent chlorine e6 (MnO2@Ce6), and a chemotherapy drug doxorubicin (DOX) into MDA-MB-231cells. The RNA hydrogel consists of one tumour suppressor miRNA (miRNA-205) and one anti-metastatic miRNA (miRNA-182), both of which showed an outstanding effect in synergistically abrogating tumours. The hydrogel would be dissociated by endogenous Dicer enzyme to release loaded therapeutic molecules, and in the meantime induce decomposition of tumor endogenous H2O2 to relieve tumor hypoxia. As a result, a remarkable synergistic therapeutic effect is achieved through the combined chemo-photodynamic therapy, which simultaneously triggers a series of anti-tumor immune responses. Besides, the hydrogel as the carrier which modified aptamer to targeted MDA-MB-231 has the advantages of good biocompatibility and low cytotoxicity. This strategy could be implemented to design any other microRNA (miRNA) as the carrier, combined with other treatment methods to treat human cancer, thereby overcoming the limitations of current cancer therapies.

scholarly journals Nanomaterials for Tumor Hypoxia Relief to Improve the Efficacy of ROS-Generated Cancer Therapy

2021 ◽  
Vol 9 ◽  
Author(s):  
Changping Ruan ◽  
Kaihua Su ◽  
Dongmin Zhao ◽  
Ai Lu ◽  
Chaoran Zhong
Keyword(s):  
Cancer Therapy ◽  
Tumor Metastasis ◽  
Tumor Hypoxia ◽  
Cancer Therapeutics ◽  
Ros Generation ◽  
Cancer Therapies ◽  
Tumor Resistance ◽  
Therapeutic Outcomes ◽  
Challenges And Opportunities ◽  
Future Challenges

Given the fact that excessive levels of reactive oxygen species (ROS) induce damage to proteins, lipids, and DNA, various ROS-generating agents and strategies have been explored to induce cell death and tumor destruction by generating ROS above toxic threshold. Unfortunately, hypoxia in tumor microenvironment (TME) not only promotes tumor metastasis but also enhances tumor resistance to the ROS-generated cancer therapies, thus leading to ineffective therapeutic outcomes. A variety of nanotechnology-based approaches that generate or release O2 continuously to overcome hypoxia in TME have showed promising results to improve the efficacy of ROS-generated cancer therapy. In this minireview, we present an overview of current nanomaterial-based strategies for advanced cancer therapy by modulating the hypoxia in the TME and promoting ROS generation. Particular emphasis is put on the O2 supply capability and mechanism of these nanoplatforms. Future challenges and opportunities of design consideration are also discussed. We believe that this review may provide some useful inspiration for the design and construction of other advanced nanomaterials with O2 supply ability for overcoming the tumor hypoxia-associated resistance of ROS-mediated cancer therapy and thus promoting ROS-generated cancer therapeutics.

scholarly journals Delivery of cancer therapies by synthetic and bio-inspired nanovectors

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Tina Briolay ◽  
Tacien Petithomme ◽  
Morgane Fouet ◽  
Nelly Nguyen-Pham ◽  
Christophe Blanquart ◽  
...  
Keyword(s):  
Recent Literature ◽  
Biological Properties ◽  
Engineered Nanoparticles ◽  
Oncolytic Viruses ◽  
Cancer Therapies ◽  
Different Types ◽  
Therapeutic Molecules ◽  
Tumor Specificity ◽  
Smart Drug ◽  
Smart Drug Delivery

Abstract Background As a complement to the clinical development of new anticancer molecules, innovations in therapeutic vectorization aim at solving issues related to tumor specificity and associated toxicities. Nanomedicine is a rapidly evolving field that offers various solutions to increase clinical efficacy and safety. Main Here are presented the recent advances for different types of nanovectors of chemical and biological nature, to identify the best suited for translational research projects. These nanovectors include different types of chemically engineered nanoparticles that now come in many different flavors of ‘smart’ drug delivery systems. Alternatives with enhanced biocompatibility and a better adaptability to new types of therapeutic molecules are the cell-derived extracellular vesicles and micro-organism-derived oncolytic viruses, virus-like particles and bacterial minicells. In the first part of the review, we describe their main physical, chemical and biological properties and their potential for personalized modifications. The second part focuses on presenting the recent literature on the use of the different families of nanovectors to deliver anticancer molecules for chemotherapy, radiotherapy, nucleic acid-based therapy, modulation of the tumor microenvironment and immunotherapy. Conclusion This review will help the readers to better appreciate the complexity of available nanovectors and to identify the most fitting “type” for efficient and specific delivery of diverse anticancer therapies.

Clonally Related But Phenotypically Divergent Human Cancer Cell Lines Derived from a Single Follicular Thyroid Cancer Recurrence (TT2609)

Thyroid ◽  
2001 ◽  
Vol 11 (10) ◽  
pp. 909-917 ◽  
Author(s):  
Albert A. Geldof ◽  
Richard T. Versteegh ◽  
Johan C. van Mourik ◽  
Martin A. Rooimans ◽  
Fre Arwert ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Human Cancer ◽  
Cancer Recurrence ◽  
Cancer Cell Lines ◽  
Human Cancer Cell ◽  
Follicular Thyroid Cancer ◽  
Human Cancer Cell Lines ◽  
Thyroid Cancer Recurrence

scholarly journals Defining the mutation signatures of DNA polymerase θ in cancer genomes

NAR Cancer ◽  
2020 ◽  
Vol 2 (3) ◽  
Author(s):  
Taejoo Hwang ◽  
Shelley Reh ◽  
Yerkin Dunbayev ◽  
Yi Zhong ◽  
Yoko Takata ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Dna Polymerase ◽  
Human Cancer ◽  
Strand Break ◽  
Base Substitution ◽  
Cancer Therapies ◽  
End Joining ◽  
Dsb Repair ◽  
Human Cancer Cells ◽  
Insertion And Deletion

Abstract DNA polymerase theta (POLQ)-mediated end joining (TMEJ) is a distinct pathway for mediating DNA double-strand break (DSB) repair. TMEJ is required for the viability of BRCA-mutated cancer cells. It is crucial to identify tumors that rely on POLQ activity for DSB repair, because such tumors are defective in other DSB repair pathways and have predicted sensitivity to POLQ inhibition and to cancer therapies that produce DSBs. We define here the POLQ-associated mutation signatures in human cancers, characterized by short insertions and deletions in a specific range of microhomologies. By analyzing 82 COSMIC (Catalogue of Somatic Mutations in Cancer) signatures, we found that BRCA-mutated cancers with a higher level of POLQ expression have a greatly enhanced representation of the small insertion and deletion signature 6, as well as single base substitution signature 3. Using human cancer cells with disruptions of POLQ, we further show that TMEJ dominates end joining of two separated DSBs (distal EJ). Templated insertions with microhomology are enriched in POLQ-dependent distal EJ. The use of this signature analysis will aid in identifying tumors relying on POLQ activity.

scholarly journals Alternative splicing in endothelial cells: novel therapeutic opportunities in cancer angiogenesis

2020 ◽  
Vol 39 (1) ◽  
Author(s):  
Anna Di Matteo ◽  
Elisa Belloni ◽  
Davide Pradella ◽  
Ambra Cappelletto ◽  
Nina Volf ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Human Cancer ◽  
Single Gene ◽  
Predictive Biomarkers ◽  
Protein Isoforms ◽  
Therapeutic Interventions ◽  
Cancer Therapies ◽  
Functional Changes ◽  
Splicing Regulators ◽  
Multiple Protein

AbstractAlternative splicing (AS) is a pervasive molecular process generating multiple protein isoforms, from a single gene. It plays fundamental roles during development, differentiation and maintenance of tissue homeostasis, while aberrant AS is considered a hallmark of multiple diseases, including cancer. Cancer-restricted AS isoforms represent either predictive biomarkers for diagnosis/prognosis or targets for anti-cancer therapies. Here, we discuss the contribution of AS regulation in cancer angiogenesis, a complex process supporting disease development and progression. We consider AS programs acting in a specific and non-redundant manner to influence morphological and functional changes involved in cancer angiogenesis. In particular, we describe relevant AS variants or splicing regulators controlling either secreted or membrane-bound angiogenic factors, which may represent attractive targets for therapeutic interventions in human cancer.

Recent Advances in the Cancer Bioimaging with Graphene Quantum Dots

2018 ◽  
Vol 25 (25) ◽  
pp. 2876-2893 ◽  
Author(s):  
Keheng Li ◽  
Xinna Zhao ◽  
Gang Wei ◽  
Zhiqiang Su
Keyword(s):  
Quantum Dots ◽  
Biomedical Applications ◽  
Cell Imaging ◽  
Graphene Quantum Dots ◽  
Biological Properties ◽  
Live Cells ◽  
Physical Chemical ◽  
Specific Cancer ◽  
Good Biocompatibility ◽  
Low Cytotoxicity

Fluorescent graphene quantum dots (GQDs) have attracted increasing interest in cancer bioimaging due to their stable photoluminescence (PL), high stability, low cytotoxicity, and good biocompatibility. In this review, we present the synthesis and chemical modification of GQDs firstly, and then introduce their unique physical, chemical, and biological properties like the absorption, PL, and cytotoxicity of GQDs. Finally and most importantly, the recent applications of GQDs in cancer bioimaging are demonstrated in detail, in which we focus on the biofunctionalization of GQDs for specific cancer cell imaging and real-time molecular imaging in live cells. We expect this work would provide valuable guides on the synthesis and modification of GQDs with adjustable properties for various biomedical applications in the future.

scholarly journals Salinomycin as a Drug for Targeting Human Cancer Stem Cells

2012 ◽  
Vol 2012 ◽  
pp. 1-17 ◽  
Author(s):  
Cord Naujokat ◽  
Roman Steinhart
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Epithelial Mesenchymal Transition ◽  
Human Cancer ◽  
Drug Transporters ◽  
Molecular Complexes ◽  
Cancer Therapies ◽  
Mesenchymal Transition ◽  
Heavily Pretreated ◽  
Preclinical Trials

Cancer stem cells (CSCs) represent a subpopulation of tumor cells that possess self-renewal and tumor initiation capacity and the ability to give rise to the heterogenous lineages of malignant cells that comprise a tumor. CSCs possess multiple intrinsic mechanisms of resistance to chemotherapeutic drugs, novel tumor-targeted drugs, and radiation therapy, allowing them to survive standard cancer therapies and to initiate tumor recurrence and metastasis. Various molecular complexes and pathways that confer resistance and survival of CSCs, including expression of ATP-binding cassette (ABC) drug transporters, activation of the Wnt/β-catenin, Hedgehog, Notch and PI3K/Akt/mTOR signaling pathways, and acquisition of epithelial-mesenchymal transition (EMT), have been identified recently. Salinomycin, a polyether ionophore antibiotic isolated fromStreptomyces albus, has been shown to kill CSCs in different types of human cancers, most likely by interfering with ABC drug transporters, the Wnt/β-catenin signaling pathway, and other CSC pathways. Promising results from preclinical trials in human xenograft mice and a few clinical pilote studies reveal that salinomycin is able to effectively eliminate CSCs and to induce partial clinical regression of heavily pretreated and therapy-resistant cancers. The ability of salinomycin to kill both CSCs and therapy-resistant cancer cells may define the compound as a novel and an effective anticancer drug.

Responsive agarose hydrogel incorporated with natural humic acid and MnO2 nanoparticles for effective relief of tumor hypoxia and enhanced photo-induced tumor therapy

2020 ◽  
Vol 8 (1) ◽  
pp. 353-369 ◽  
Author(s):  
Mengmeng Hou ◽  
Weiwei Liu ◽  
Lei Zhang ◽  
Leiyang Zhang ◽  
Zhigang Xu ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Humic Acid ◽  
Tumor Microenvironment ◽  
Tumor Therapy ◽  
Tumor Hypoxia ◽  
Therapeutic Outcome ◽  
Severe Hypoxia ◽  
Tumor Penetration ◽  
Mno2 Nanoparticles ◽  
Agarose Hydrogel

In spite of widespread applications of nano-photosensitizers, poor tumor penetration and severe hypoxia in the tumor microenvironment (TME) always result in an undesirable therapeutic outcome of photodynamic therapy (PDT).

scholarly journals Role of POT1 in Human Cancer

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2739 ◽  
Author(s):  
Yangxiu Wu ◽  
Rebecca C. Poulos ◽  
Roger R. Reddel
Keyword(s):  
Human Cancer ◽  
Cell Types ◽  
Cancer Therapies ◽  
Telomeric Dna ◽  
Targeted Cancer Therapies ◽  
Length Regulation ◽  
Tumor Types ◽  
Different Cell Types ◽  
Essential Subunit

Telomere abnormalities facilitate cancer development by contributing to genomic instability and cellular immortalization. The Protection of Telomeres 1 (POT1) protein is an essential subunit of the shelterin telomere binding complex. It directly binds to single-stranded telomeric DNA, protecting chromosomal ends from an inappropriate DNA damage response, and plays a role in telomere length regulation. Alterations of POT1 have been detected in a range of cancers. Here, we review the biological functions of POT1, the prevalence of POT1 germline and somatic mutations across cancer predisposition syndromes and tumor types, and the dysregulation of POT1 expression in cancers. We propose a framework for understanding how POT1 abnormalities may contribute to oncogenesis in different cell types. Finally, we summarize the clinical implications of POT1 alterations in the germline and in cancer, and possible approaches for the development of targeted cancer therapies.

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