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JOUrnaL OF DRUG TARGETING 2013年第10期21卷 904-913页

作者： Aslan, Burcu Ozpolat, Bulent Sood, Anil K. Lopez-Berestein, Gabriel Univ Texas MD Anderson Canc Ctr Dept Expt Therapeut Houston TX 77030 USA Univ Texas MD Anderson Canc Ctr Ctr RNA Interference & Non Coding RNA Houston TX 77030 USA Univ Texas MD Anderson Canc Ctr Dept Gynecol Oncol Houston TX 77030 USA Univ Texas MD Anderson Canc Ctr Dept Canc Biol Houston TX 77030 USA Univ Texas Hlth Sci Ctr Houston UTHealth Dept Nanomed & Bioengn Houston TX USA

Cancer is one of the major causes of mortality worldwide and advanced techniques for therapy are urgently needed. The development of novel nanomaterials and nanocarriers has allowed a major drive to improve drug delivery in cancer. The major aim of most nanocarrier applications has been to protect the drug from rapid degradation after systemic delivery and allowing it to reach tumor site at therapeutic concentrations, meanwhile avoiding drug delivery to normal sites as much as possible to reduce adverse effects. These nanocarriers are formulated to deliver drugs either by passive targeting, taking advantage of leaky tumor vasculature or by active targeting using ligands that increase tumoral uptake potentially resulting in enhanced antitumor efficacy, thus achieving a net improvement in therapeutic index. The rational design of nanoparticles plays a critical role since structural and physical characteristics, such as size, charge, shape, and surface characteristics determine the biodistribution, pharmacokinetics, internalization and safety of the drugs. In this review, we focus on several novel and improved strategies in nanocarrier design for cancer therapy.

关键词： Cancer therapy drug delivery nanoparticles nanomedicine

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rna interference in the clinic: challenges and future directions

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NATURE REVIEWS CANCER 2011年第1期11卷 59-67页

作者： Pecot, Chad V. Calin, George A. Coleman, Robert L. Lopez-Berestein, Gabriel Sood, Anil K. Univ Texas MD Anderson Canc Ctr Ctr RNA Interference & Non Coding RNA Houston TX 77030 USA Univ Texas MD Anderson Canc Ctr Div Canc Med Houston TX 77030 USA Univ Texas MD Anderson Canc Ctr Dept Expt Therapeut Houston TX 77030 USA Univ Texas MD Anderson Canc Ctr Dept Gynecol Oncol Houston TX 77030 USA Univ Texas MD Anderson Canc Ctr Dept Canc Biol Houston TX 77030 USA

Inherent difficulties with blocking many desirable targets using conventional approaches have prompted many to consider using rna interference (rnai) as a therapeutic approach. Although exploitation of rnai has immense potential as a cancer therapeutic, many physiological obstacles stand in the way of successful and efficient delivery. This Review explores current challenges to the development of synthetic rnai-based therapies and considers new approaches to circumvent biological barriers, to avoid intolerable side effects and to achieve controlled and sustained release.

关键词： rna CANCER treatment NUCLEIC acids RIBOSOMAL DNA RIBOSE THERAPEUTIC use

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Unraveling the therapeutic potential of the Lncrna-dependent noncanonical Hedgehog pathway in cancer

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MOLECULAR & CELLULAR ONCOLOGY 2015年第4期2卷 Article: e998900页

作者： Xing, Zhen Lin, Chunru Yang, Liuqing Univ Texas MD Anderson Canc Ctr Dept Mol & Cellular Oncol Houston TX 77030 USA Univ Texas Houston Cancer Biol Program Houston TX 77004 USA Univ Texas MD Anderson Canc Ctr Ctr RNA Interference & Non Coding RNAs Houston TX 77030 USA

Acquired resistance to Hedgehog pathway inhibitors has been reported in the clinical setting and upregulation of noncanonical Hedgehog signaling is one of the major underlying mechanisms behind this resistance. As demonstrated in our recent study, greater clinical efficacy might be achieved by focusing on downstream targets of the chemokine activated noncanonical Hedgehog signaling pathway such as BCAR4 and phospho-GLI2 (Ser149).

关键词： Long non-coding rna BCAR4 signaling pathway Hedgehog Gli2 breast cancer lung metastasis cancer treatment locked nucleic acid

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Microrna therapeutics:principles,expectations,and challenges

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Chinese Journal of Cancer 2011年第6期30卷 368-370页

作者： Rajesha Rupaimoole Hee-Dong Han Gabriel Lopez-Berestein Anil K.Sood Department of Gynecologic Oncology The University of Texas M.D.Anderson Cancer Center Department of Center for RNA Interference and Non-Coding RNA The University of Texas M.D.Anderson Cancer Center Department of Experimental Therapeutics The University of Texas M.D.Anderson Cancer Center Department of Department of Cancer Biology The University of Texas M.D.Anderson Cancer Center

Micrornas(mirnas) are a class of highly abundant non-coding rna molecules that are involved in several biological *** mirnas are often deregulated in several diseases including *** is substantial interest in exploiting mirnas for therapeutic *** this editorial,we briefly review current advances in the use of mirnas or antisense oligonucleotides(antagomirs) for such *** of the key issues related to therapy using mirnas is degradation of naked particles in *** overcome this limitation,delivery systems for mirna-based therapeutic agents have been developed,which hold tremendous potential for improving therapeutic outcome of cancer patients.

关键词：微rna 疗法 mirnas 小分子rna 治疗药物期望非编码rna 反义寡核苷酸

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The role of exosomal long non-coding rnas in cancer drug resistance

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Cancer Drug Resistance 2019年第4期2卷 1178-1192页

作者： Mireia Cruz De los Santos Mihnea P.Dragomir George A.Calin Department of Experimental Therapeutics The University of Texas MD Anderson Cancer CenterHoustonTX 77054USA Research Center for Functional Genomics Biomedicine and Translational MedicineIuliu Hatieganu University of Medicine and PharmacyCluj-Napoca 40015Romania Department of Surgery Fundeni Clinical HospitalCarol Davila University of Medicine and PharmacyBucharest 022328Romania Center for RNA Interference and Non-coding RNAs The University of Texas MD Anderson Cancer CenterHoustonTX 77054USA

One of the major challenges in oncology is drug resistance,which triggers relapse and shortens patients’*** order to promote drug desensitization,cancer cells require the establishment of an ideal tumor microenvironment that accomplishes specific *** achieve this objective,cellular communication is a key ***,cells were believed to restrictively communicate by ligand-receptor binding,physical cell-to-cell interactions and ***,the crosstalk between tumor cells and stroma cells has also been recently reported to be mediated through exosomes,the smallest extracellular vesicles,which transport a plethora of functionally active molecules,such as:proteins,lipids,messenger rna,DNA,microrna or long non-coding rna(lncrnas).Lncrnas are rna molecules greater than 200 base pairs that are deregulated in cancer and other *** lncrnas are highly stable and can be found in several body fluids,being considered potential biomarkers for tumor liquid *** lncrnas promote angiogenesis,cell proliferation and drug *** role of exosomal lncrnas in drug resistance affects the main treatment strategies in oncology:chemotherapy,targeted therapy,hormone therapy and ***,knowing the molecular mechanisms by which exosomal lncrna induce pharmacologic resistance could improve further drug development and identify drug resistance biomarkers.

关键词： Tumor microenvironment extracellular vesicles exosomes non-coding rna long non-coding rna drug resistance

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The rna-Binding Protein DDX1 Promotes Primary Microrna Maturation and Inhibits Ovarian Tumor Progression

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CELL REPORTS 2014年第5期8卷 1447-1460页

作者： Han, Cecil Liu, Yunhua Wan, Guohui Choi, Hyun Jin Zhao, Luqing Ivan, Cristina He, Xiaoming Sood, Anil K. Zhang, Xinna Lu, Xiongbin Univ Texas MD Anderson Canc Ctr Dept Canc Biol Houston TX 77030 USA Univ Texas MD Anderson Canc Ctr Dept Gynecol Oncol & Reprod Med Houston TX 77030 USA Univ Texas MD Anderson Canc Ctr Ctr RNA Interference & Non Coding RNAs Houston TX 77030 USA Ohio State Univ Dept Biomed Engn Columbus OH 43210 USA

Posttranscriptional maturation is a critical step in microrna (mirna) biogenesis that determines mature mirna levels. In addition to core components (Drosha and DGCR8 [DiGeorge syndrome critical region gene 8]) in the microprocessor, regulatory rna-binding proteins may confer the specificity for recruiting and processing of individual primary mirnas (primirnas). Here, we identify DDX1 as a regulatory protein that promotes the expression of a subset of mirnas, including five members in the microrna-200 (miR-200) family and four mirnas in an eight-mirna signature of a mesenchymal ovarian cancer subtype. A majority of DDX1-dependent mirnas are induced after DNA damage. This induction is facilitated by the ataxia telangiectasia mutated (ATM)-mediated phosphorylation of DDX1. Inhibiting DDX1 promotes ovarian tumor growth and metastasis in a syngeneic mouse model. Analysis of The Cancer Genome Atlas (TCGA) reveals that low DDX1 levels are associated with poor clinical outcome in patients with serous ovarian cancer. These findings suggest that DDX1 is a key modulator in mirna maturation and ovarian tumor suppression.

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Biobehavioral Influences on Cancer Progression

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IMMUNOLOGY AND ALLERGY CLINICS OF NORTH AMERICA 2011年第1期31卷 109-+页

作者： Costanzo, Erin S. Sood, Anil K. Lutgendorf, Susan K. Univ Wisconsin Dept Psychiat Carbone Comprehens Canc Ctr Madison WI 53719 USA Univ Texas Houston Dept Gynecol Oncol MD Anderson Canc Ctr Houston TX 77230 USA Univ Texas Houston Ctr RNA Interference & Non Coding RNA MD Anderson Canc Ctr Houston TX 77230 USA Univ Iowa Dept Psychol Holden Comprehens Canc Ctr Iowa City IA 52242 USA Univ Iowa Dept Urol Holden Comprehens Canc Ctr Iowa City IA 52242 USA Univ Iowa Dept Obstet & Gynecol Holden Comprehens Canc Ctr Iowa City IA 52242 USA

This review focuses on the contributions of stress-related behavioral factors to cancer growth and metastasis and the biobehavioral mechanisms underlying these relationships. Behavioral factors that are important in modulation of the stress response and the pivotal role of neuroendocrine regulation in the downstream alteration of physiologic pathways relevant to cancer control, including the cellular immune response, inflammation, and tumor angiogenesis, invasion, and cell signaling pathways are described. Consequences for cancer progression and metastasis, as well as quality of life, are delineated. Behavioral and pharmacologic interventions with the potential to alter these biobehavioral pathways for patients with cancer are discussed.

关键词： Cancer Stress Depression Immunity Inflammation Angiogenesis

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EGFL6 promotes breast cancer by simultaneously enhancing cancer cell metastasis and stimulating tumor angiogenesis

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ONCOGENE 2019年第12期38卷 2123-2134页

作者： An, Jingnan Du, Yi Fan, Xuejun Wang, Yanhong Ivan, Cristina Zhang, Xue-Guang Sood, Anil K. An, Zhiqiang Zhang, Ningyan Soochow Univ Jiangsu Inst Clin Immunol Affiliated Hosp 1 708 Renmin Rd Suzhou Peoples R China Univ Texas Hlth Sci Ctr Houston Brown Fdn Inst Mol Med Texas Therapeut Inst 1825 Pressler St Houston TX 77030 USA Shanxi Med Univ Dept Microbiol & Immunol Taiyuan Shanxi Peoples R China Univ Texas MD Anderson Canc Ctr Ctr RNA Interference & Non Coding RNA Dept Expt Therapeut Houston TX 77030 USA Univ Texas MD Anderson Canc Ctr Gynecol Oncol & Reprod Med Houston TX 77030 USA

EGFL6, a member of the EGF-like superfamily, plays an important role during embryonic development and has been implicated in promotion of tumor angiogenesis without affecting wound healing. There is very little known about the function of EGFL6 in cancer cells. Here, we investigated whether EGFL6 plays a direct role in cancer cells in addition to the promotion of tumor angiogenesis. Our study showed that EGFL6 promoted epithelial-mesenchymal transition (EMT) and stemness of breast cancer cells and increased cell migration and invasion in cell culture studies. We also found that EGFL6 reduced apoptotic signaling in cancer cells and promoted tumor growth in vivo. Importantly, expression of EGFL6 in cancer cells and tumor endothelial cells not only increased tumor angiogenesis but also promoted migration of cancer cells. Such dual engagement of cancer and stromal cells suggests crosstalk mediated by EGFL6 in the tumor microenvironment. Blockade of EGFL6 using our novel anti-EGFL6 monoclonal antibody significantly reduced cancer cell migration, tumor angiogenesis, and tumor growth in mouse xenograft tumor models. Silencing EGFL6 mrna by shrna transfection of cancer cells also significantly reduced cancer cell migration, tumor angiogenesis, and tumor growth in mouse xenograft tumor models. Taken together, the results of this study indicate that targeting EGFL6 is a unique strategy for inhibiting both cancer cell metastasis and tumor angiogenesis.

关键词： Biomarkers Breast cancer

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MiR-144/451 in hematopoiesis and beyond

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Exrna 2019年第April-May-June期1卷 1-12页

作者： Wang, Ting Wu, Fan Yu, Duonan Jiangsu Key Laboratory of Experimental & Translational Non-coding RNA Research Yangzhou University School of Medicine Yangzhou China Institute of Translational Medicine Yangzhou University School of Medicine Yangzhou China Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Disease and Zoonosis Yangzhou China

Micrornas (mirnas), a class of 18–25 nucleotide (nt) non-coding rnas, usually inhibit the expression of their target genes. They are transcribed from endogenous genes and are processed for maturation by multiple pathways. miR-144/451, a bicistronic gene locus, encodes miR-144 and miR-451, both of which are highly conserved in evolution. These two mirnas are on the same primary rna molecule whose transcription is controlled by multiple nuclear proteins, including GATA1, GATA4, Myc, Oct1, Pax4, FXR, AP1, SMAD3 and SMAD4 depending on tissue types. They are abundant and almost exclusively exist in red blood cells, but low expression of both miR-144 and miR-451 are also detected in non-erythroid lineages. Interestingly, deletion of both miR-144 and miR-451 DNA sequences coding pre-miR-144/451 hairpins in mice leads only mild microcytic anemia but worsen upon a number of stresses including developmental stress, acute blood loss, phenohydrazine-induced hemolysis and precursor depletion by chemotherapeutic drug 5-FU. Such knockout animals older than 15 months also spontaneously develop malignant tumors including B-lymphoma and acute myeloid leukemia, indicating that miR-144/451 is a bona fide tumor-suppressing gene in non-erythroid cells, though its levels are much lower compared to that in red blood cells. Consistent with the findings in animals, disruption of miR-144/451 expression and their abnormal functions are observed in human hematopoietic and non-hematopoietic organs. Moreover, miR-451 is the only mirna discovered so far whose maturation does not depend on Dicer, an enzyme required by all other mirnas for maturation. This review focuses on the biogenesis, transcriptional regulation and biological roles of miR-144/451 in erythropoiesis, tumor initiation and other pathological conditions. © The Author(s).

关键词： Biogenesis Cancer Erythropoiesis MiR-144 MiR-451 Transcription

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rna nanoparticles harboring annexin A2 aptamer can target ovarian cancer for tumor-specific doxorubicin delivery

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NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE 2017年第3期13卷 1183-1193页

作者： Pi, Fengmei Zhang, Hui Li, Hui Thiviyanathan, Varatharasa Gorenstein, David G. Sood, Anil K. Guo, Peixuan Ohio State Univ Coll Pharm Div Pharmaceut & Pharmaceut Chem Columbus OH 43210 USA Ohio State Univ Coll Med Dorothy M Davis Heart & Lung Res Inst Dept Physiol & Cell Biol Columbus OH 43210 USA Univ Kentucky Dept Pharmaceut Sci Lexington KY USA Univ Texas Hlth Sci Ctr Houston Dept Diagnost & Biomed Sci Houston TX 77030 USA AM Biotechnol Houston TX USA Univ Texas MD Anderson Canc Ctr Dept Gynecol Oncol Houston TX 77030 USA Univ Texas MD Anderson Canc Ctr Ctr RNA Interference & Non Coding RNA Houston TX 77030 USA

A novel modified nucleic acid nanoparticle harboring an annexin A2 aptamer for ovarian cancer cell targeting and a GC rich sequence for doxorubicin loading is designed and constructed. The system utilizes a highly stable three-way junction (3WJ) motif from phi29 packaging rna as a core structure. A phosphorothioate-modified DNA aptamer targeting annexin A2, Endo28, was conjugated to one arm of the 3WJ. The prna-3WJ motif retains correct folding of attached aptamer, keeping its functions intact. It is of significant utility for aptamer-mediated targeted delivery. The DNA/rna hybrid nanoparticles remained intact after systemic injection in mice and strongly bound to tumors with little accumulation in healthy organs 6 h post-injection. The Endo28- 3WJ-Sph1/Dox intercalates selectively enhanced toxicity to annexin A2 positive ovarian cancer cells in vitro. The constructed rna/DNA hybrid nanoparticles can potentially enhance the therapeutic efficiency of doxorubicin at low doses for ovarian cancer treatment through annexin A2 targeted drug delivery. (C) 2016 Elsevier Inc. All rights reserved.

关键词： rna nanotechnology Aptamer Annexin A2 Doxorubicin Ovarian cancer

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