70,265 results on '"Neoplasms, Experimental"'
Search Results
2. Sorafenib and TRC105 in Hepatocellular Cancer
- Author
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Tim Greten, M.D., Principal Investigator
- Published
- 2019
3. Chidamide Combined With CHOPE Regimen for Peripheral T-cell Lymphoma Patients
- Author
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Peking University International Hospital, Shandong Tumor Hospital, Jiangxi Provincial Cancer Hospital, and Jun Zhu, Director of lymphoma department
- Published
- 2018
4. Chidamide Maintenance After Autologous Hematopoietic Stem Cell Transplantation for Relapsed, Refractory or High-risk Lymphoma
- Author
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Hebei Medical University Fourth Hospital, Peking University International Hospital, and Jun Zhu, Director
- Published
- 2018
5. Chidamide for Patients With Recurrent and Metastatic Epstein-Barr Virus (EBV)-Associated Solid Tumors
- Author
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Li Zhang, director
- Published
- 2018
6. Amelioration of Tumor-promoting Microenvironment via Vascular Remodeling and CAF Suppression Using E7130: Biomarker Analysis by Multimodal Imaging Modalities.
- Author
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Ito K, Yamaguchi M, Semba T, Tabata K, Tamura M, Aoyama M, Abe T, Asano O, Terada Y, Funahashi Y, and Fujii H
- Subjects
- Animals, Humans, Vascular Remodeling, Tumor Microenvironment, Endothelial Cells pathology, Cancer-Associated Fibroblasts pathology, Neoplasms drug therapy, Neoplasms, Experimental, Antimitotic Agents pharmacology
- Abstract
E7130 is a novel anticancer agent created from total synthetic study of the natural compound norhalichondrin B. In addition to inhibiting microtubule dynamics, E7130 also ameliorates tumor-promoting aspects of the tumor microenvironment (TME) by suppressing cancer-associated fibroblasts (CAF) and promoting remodeling of tumor vasculature. Here, we demonstrate TME amelioration by E7130 using multi-imaging modalities, including multiplexed mass cytometry [cytometry by time-of-flight (CyTOF)] analysis, multiplex IHC analysis, and MRI. Experimental solid tumors characterized by large numbers of CAFs in TME were treated with E7130. E7130 suppressed LAP-TGFβ1 production, a precursor of TGFβ1, in CAFs but not in cancer cells; an effect that was accompanied by a reduction of circulating TGFβ1 in plasma. To our best knowledge, this is the first report to show a reduction of TGFβ1 production in TME. Furthermore, multiplex IHC analysis revealed reduced cellularity and increased TUNEL-positive apoptotic cells in E7130-treated xenografts. Increased microvessel density (MVD) and collagen IV (Col IV), an extracellular matrix (ECM) component associated with endothelial cells, were also observed in the TME, and plasma Col IV levels were also increased by E7130 treatment. MRI revealed increased accumulation of a contrast agent in xenografts. Moreover, diffusion-weighted MRI after E7130 treatment indicated reduction of tumor cellularity and interstitial fluid pressure. Overall, our findings strongly support the mechanism of action that E7130 alters the TME in therapeutically beneficial ways. Importantly, from a translational perspective, our data demonstrated MRI as a noninvasive biomarker to detect TME amelioration by E7130, supported by consistent changes in plasma biomarkers., (©2023 American Association for Cancer Research.)
- Published
- 2024
- Full Text
- View/download PDF
7. Experimental Tumor Induction and Evaluation of Its Treatment in the Chicken Embryo Chorioallantoic Membrane Model: A Systematic Review.
- Author
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Mesas C, Chico MA, Doello K, Lara P, Moreno J, Melguizo C, Perazzoli G, and Prados J
- Subjects
- Animals, Chick Embryo, Humans, Biological Assay, Chorioallantoic Membrane, Precision Medicine, Neoplasms, Experimental
- Abstract
The chorioallantoic membrane (CAM) model, generated during avian development, can be used in cancer research as an alternative in vivo model to perform tumorigenesis in ovo due to advantages such as simplicity, low cost, rapid growth, and being naturally immunodeficient. The aim of this systematic review has been to compile and analyze all studies that use the CAM assay as a tumor induction model. For that, a systematic search was carried out in four different databases: PubMed, Scopus, Cochrane, and WOS. After eliminating duplicates and following the established inclusion and exclusion criteria, a total of 74 articles were included. Of these, 62% use the in ovo technique, 13% use the ex ovo technique, 9% study the formation of metastasis, and 16% induce tumors from patient biopsies. Regarding the methodology followed, the main species used is chicken (95%), although some studies use quail eggs (4%), and one article uses ostrich eggs. Therefore, the CAM assay is a revolutionary technique that allows a simple and effective way to induce tumors, test the effectiveness of treatments, carry out metastasis studies, perform biopsy grafts of patients, and carry out personalized medicine. However, unification of the methodology used is necessary.
- Published
- 2024
- Full Text
- View/download PDF
8. Second generation β-elemene nitric oxide derivatives with reasonable linkers: potential hybrids against malignant brain glioma
- Author
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Renren Bai, Junlong Zhu, Ziqiang Bai, Qing Mao, Yingqian Zhang, Zi Hui, Xinyu Luo, Xiang-Yang Ye, and Tian Xie
- Subjects
natural product ,Short Communication ,no donor ,Mice, Nude ,Antineoplastic Agents ,RM1-950 ,Nitric Oxide ,Mice ,Structure-Activity Relationship ,Cell Line, Tumor ,Drug Discovery ,Animals ,Humans ,Cell Proliferation ,Pharmacology ,Oxadiazoles ,Dose-Response Relationship, Drug ,Molecular Structure ,Brain Neoplasms ,β-elemene ,Brief Report ,Glioma ,Neoplasms, Experimental ,General Medicine ,malignant glioma ,anti-tumour ,Therapeutics. Pharmacology ,Sesquiterpenes - Abstract
Elemene is a second-line broad-spectrum anti-tumour drug that has been used in China for more than two decades. However, its main anti-tumour ingredient, β-elemene, has disadvantages, including excessive lipophilicity and relatively weak anti-tumour efficacy. To improve the anti-tumour activity of β-elemene, based on its minor molecular weight character, we introduced furoxan nitric oxide (NO) donors into the β-elemene structure and designed six series of new generation β-elemene NO donor hybrids. The synthesised compounds could effectively release NO in vitro, displayed significant anti-proliferative effects on U87MG, NCI-H520, and SW620 cell lines. In the orthotopic glioma model, compound Id significantly and continuously suppressed the growth of gliomas in nude mice, and the brain glioma of the treatment group was markedly inhibited (>90%). In short, the structural fusion design of NO donor and β-elemene is a feasible strategy to improve the in vivo anti-tumour activity of β-elemene.
- Published
- 2022
9. Universal and Translational Nanoparticulate CpG Adjuvant
- Author
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Dongdong Qiao, Liyan Li, Lixin Liu, and Yongming Chen
- Subjects
Mice, Inbred C57BL ,Mice ,Influenza A Virus, H1N1 Subtype ,Adjuvants, Immunologic ,Oligodeoxyribonucleotides ,Toll-Like Receptor 9 ,Animals ,Nanoparticles ,Hemagglutinin Glycoproteins, Influenza Virus ,CpG Islands ,General Materials Science ,Neoplasms, Experimental - Abstract
CpG, an agonist of toll-like receptor 9 (TLR9), has become a novel adjuvant that substantially potentiates cellular immunity. However, this agonist may increase systemic toxicity by diffusing into blood after administration and is difficult to be internalized by immune cells to reach TLR9 located in endosomes as a result of the characteristics of negative charge of CpG. Here, we applied a scalable and controllable flash nanocomplexation technology to prepare nanoparticulate CpG adjuvant (
- Published
- 2022
10. A systematic review on the effects of direct oral anticoagulants on cancer growth and metastasis in animal models.
- Author
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Najidh, Safa, Versteeg, Henri H., and Buijs, Jeroen T.
- Subjects
- *
TUMOR growth , *METASTASIS , *META-analysis , *ANIMAL models in research , *ORAL cancer , *METASTATIC breast cancer - Abstract
Direct oral anticoagulants (DOACs) are now the first choice thromboprophylaxis in cancer patients who do not have a high risk of bleeding. In addition to the anticoagulant effects, potential anti-tumor effects of DOACs have also been studied in animal cancer models. In this study, we summarize the effects of DOACs on cancer growth and metastasis in animal models through a systematic review with a qualitative analysis. PubMed, EMBASE and Web of Science were systematically searched for original studies that describe animal models of cancer in which one of the experimental groups received DOAC monotherapy, and which reported quantitatively on primary tumor or metastases. Nine studies - reporting a total of 19 animal experiments - met the inclusion criteria. These 19 experiments included spontaneous cancer (n = 2), carcinogenicity (n = 2), xenograft (n = 7) and syngeneic (n = 8) models, encompassing orthotopic (n = 7), subcutaneous (n = 5), intraperitoneal (n = 1) and intravenous (n = 2) injection of cancer cells and included treatments with the DOACs ximelagatran (n = 4), dabigatran etexilate (n = 6) and/or rivaroxaban (n = 11). DOAC treatment decreased tumor growth at implanted and metastatic site in 18.8% (3/16) and 20.0% (3/15) of the experiments, respectively. Conversely, DOACs increased tumor growth at implanted and metastatic site in 6.3% (1/16) and 20.0% (3/15) of the experiments, respectively. DOAC monotherapy resulted in neoplastic changes in a rat carcinogenicity study, showed a lack of effect in mouse xenograft models, while the effect on cancer growth and metastasis in mouse syngeneic models depended on the timing of DOAC treatment and type of cancer model used. • Direct oral anticoagulants (DOACs) were recently approved for patients with cancer. • Effects of DOACs on tumor growth and metastasis are unclear. • This review provides a systematic overview of experimental data in animal models. • Effects DOAC in syngeneic models are dependent on the experimental model used. • DOACs do not affect tumor progression or metastasis in xenograft models. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
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11. Anticancer Activity of ST101, A Novel Antagonist of CCAAT/Enhancer Binding Protein β
- Author
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Emad Darvishi, Lila Ghamsari, Siok F. Leong, Ricardo Ramirez, Mark Koester, Erin Gallagher, Miao Yu, Jody M. Mason, Gene Merutka, Barry J. Kappel, and Jim A. Rotolo
- Subjects
Mice ,Cancer Research ,Oncology ,CCAAT-Enhancer-Binding Protein-beta ,Animals ,Humans ,Cell Cycle Proteins ,Antineoplastic Agents ,Neoplasms, Experimental ,Article ,Cell Line ,Protein Binding - Abstract
CCAAT/enhancer binding protein β (C/EBPβ) is a basic leucine zipper (bZIP) family transcription factor, which is upregulated or overactivated in many cancers, resulting in a gene expression profile that drives oncogenesis. C/EBPβ dimerization regulates binding to DNA at the canonical TTGCGCAA motif and subsequent transcriptional activity, suggesting that disruption of dimerization represents a powerful approach to inhibit this previously “undruggable” oncogenic target. Here we describe the mechanism of action and antitumor activity of ST101, a novel and selective peptide antagonist of C/EBPβ that is currently in clinical evaluation in patients with advanced solid tumors. ST101 binds the leucine zipper domain of C/EBPβ, preventing its dimerization and enhancing ubiquitin-proteasome dependent C/EBPβ degradation. ST101 exposure attenuates transcription of C/EBPβ target genes, including a significant decrease in expression of survival, transcription factors, and cell-cycle-related proteins. The result of ST101 exposure is potent, tumor-specific in vitro cytotoxic activity in cancer cell lines including glioblastoma, breast, melanoma, prostate, and lung cancer, whereas normal human immune and epithelial cells are not impacted. Further, in mouse xenograft models ST101 exposure results in potent tumor growth inhibition or regression, both as a single agent and in combination studies. These data provide the First Disclosure of ST101, and support continued clinical development of ST101 as a novel strategy for targeting C/EBPβ-dependent cancers.
- Published
- 2022
12. Lineage plasticity in prostate cancer depends on JAK/STAT inflammatory signaling
- Author
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Joseph M. Chan, Samir Zaidi, Jillian R. Love, Jimmy L. Zhao, Manu Setty, Kristine M. Wadosky, Anuradha Gopalan, Zi-Ning Choo, Sitara Persad, Jungmin Choi, Justin LaClair, Kayla E. Lawrence, Ojasvi Chaudhary, Tianhao Xu, Ignas Masilionis, Irina Linkov, Shangqian Wang, Cindy Lee, Afsar Barlas, Michael J. Morris, Linas Mazutis, Ronan Chaligne, Yu Chen, David W. Goodrich, Wouter R. Karthaus, Dana Pe’er, and Charles L. Sawyers
- Subjects
Male ,Multidisciplinary ,Cell Plasticity ,Prostatic Neoplasms ,Androgen Antagonists ,Neoplasms, Experimental ,Article ,ErbB Receptors ,Organoids ,Mice ,STAT Transcription Factors ,Drug Resistance, Neoplasm ,Cytokines ,Animals ,Humans ,Janus Kinase Inhibitors ,Janus Kinases ,Signal Transduction - Abstract
Drug resistance in cancer is often linked to changes in tumor cell state or lineage, but the molecular mechanisms driving this plasticity remain unclear. Using murine organoid and genetically engineered mouse models, we investigated the causes of lineage plasticity in prostate cancer and its relationship to antiandrogen resistance. We found that plasticity initiates in an epithelial population defined by mixed luminal-basal phenotype and that it depends on increased Janus kinase (JAK) and fibroblast growth factor receptor (FGFR) activity. Organoid cultures from patients with castration-resistant disease harboring mixed-lineage cells reproduce the dependency observed in mice by up-regulating luminal gene expression upon JAK and FGFR inhibitor treatment. Single-cell analysis confirms the presence of mixed-lineage cells with increased JAK/STAT (signal transducer and activator of transcription) and FGFR signaling in a subset of patients with metastatic disease, with implications for stratifying patients for clinical trials.
- Published
- 2022
13. Sox9 directs divergent epigenomic states in brain tumor subtypes
- Author
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Debosmita Sardar, Hsiao-Chi Chen, Amanda Reyes, Srinidhi Varadharajan, Antrix Jain, Carrie Mohila, Rachel Curry, Brittney Lozzi, Kavitha Rajendran, Alexis Cervantes, Kwanha Yu, Ali Jalali, Ganesh Rao, Stephen C. Mack, and Benjamin Deneen
- Subjects
Mice ,Multidisciplinary ,Brain Neoplasms ,Carcinogenesis ,Ependymoma ,Animals ,SOX9 Transcription Factor ,Neoplasms, Experimental ,Epigenesis, Genetic - Abstract
Epigenetic dysregulation is a universal feature of cancer that results in altered patterns of gene expression that drive malignancy. Brain tumors exhibit subtype-specific epigenetic alterations; however, the molecular mechanisms responsible for these diverse epigenetic states remain unclear. Here, we show that the developmental transcription factor Sox9 differentially regulates epigenomic states in high-grade glioma (HGG) and ependymoma (EPN). Using our autochthonous mouse models, we found that Sox9 suppresses HGG growth and expands associated H3K27ac states, while promoting ZFTA-RELA (ZRFUS) EPN growth and diminishing H3K27ac states. These contrasting roles for Sox9 correspond with protein interactions with histone deacetylating complexes in HGG and an association with the ZRFUSoncofusion in EPN. Mechanistic studies revealed extensive Sox9 and ZRFUSpromoter co-occupancy, indicating functional synergy in promoting EPN tumorigenesis. Together, our studies demonstrate how epigenomic states are differentially regulated in distinct subtypes of brain tumors, while revealing divergent roles for Sox9 in HGG and EPN tumorigenesis.
- Published
- 2023
14. An activated form of ADAM10 is tumor selective and regulates cancer stem-like cells and tumor growth
- Author
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Ulrike Kusebauch, Zhanqi Liu, Matthias Ernst, Shahin Rafii, Martin Lackmann, Andrew M. Scott, Lakmali Atapattu, Katja Horvay, Linda Hii, Moritz F. Eissman, Dimitar B. Nikolov, Chanly Chheang, Zhongwei Cao, Helen E. Abud, Bi-Sen Ding, Kai Xu, Nayanendu Saha, Carmen Llerena, Robert L. Moritz, Mary E. Vail, and Peter W. Janes
- Subjects
Male ,0301 basic medicine ,Amino Acid Motifs ,Immunology ,Notch signaling pathway ,Tumor initiation ,ADAM17 Protein ,Biology ,Article ,ADAM10 Protein ,Mice ,03 medical and health sciences ,0302 clinical medicine ,ErbB ,Animals ,Humans ,Immunology and Allergy ,Receptor ,Research Articles ,Uncategorized ,Mice, Inbred BALB C ,Receptors, Notch ,Erythropoietin-producing hepatocellular (Eph) receptor ,Antibodies, Monoclonal ,Neoplasms, Experimental ,Molecular biology ,Transmembrane protein ,3. Good health ,Cell biology ,030104 developmental biology ,030220 oncology & carcinogenesis ,Neoplastic Stem Cells ,Signal transduction - Abstract
Janes et al. developed an anti-ADAM10 mAb (8C7) that binds to an active form of ADAM10 present in tumors, particularly in stem-like cells. Administration of 8C7 inhibits Notch activity and tumor growth in mouse models, including regrowth after chemotherapy., The transmembrane metalloprotease ADAM10 sheds a range of cell surface proteins, including ligands and receptors of the Notch, Eph, and erbB families, thereby activating signaling pathways critical for tumor initiation and maintenance. ADAM10 is thus a promising therapeutic target. Although widely expressed, its activity is normally tightly regulated. We now report prevalence of an active form of ADAM10 in tumors compared with normal tissues, in mouse models and humans, identified by our conformation-specific antibody mAb 8C7. Structure/function experiments indicate mAb 8C7 binds an active conformation dependent on disulfide isomerization and oxidative conditions, common in tumors. Moreover, this active ADAM10 form marks cancer stem-like cells with active Notch signaling, known to mediate chemoresistance. Importantly, specific targeting of active ADAM10 with 8C7 inhibits Notch activity and tumor growth in mouse models, particularly regrowth after chemotherapy. Our results indicate targeted inhibition of active ADAM10 as a potential therapy for ADAM10-dependent tumor development and drug resistance.
- Published
- 2023
- Full Text
- View/download PDF
15. The Pathobiology of Neoplasia
- Author
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A.E. Sirica and A.E. Sirica
- Subjects
- Cancer cells, Carcinogenesis, Cancer invasiveness, Cell Transformation, Neoplastic, Neoplasms--etiology, Neoplasms--pathology, Neoplasms, Experimental
- Abstract
This book is directed primarily to advanced graduate and medical students, postdoctoral trainees, and established investigators having basic research interests in neoplasia. Its content is based in part on the lecture outlines and selected histopathology laboratory components of an advanced course entitled The Pathobiology of Experimental Animal and Human Neoplasia, developed by me for the Experimental Pathology Curriculum of the Department of Pathology at the Medical College of Virginia. In this regard, an effort has been made to integrate pathology with carcinogenesis, genetics, biochemistry, and cellular and molecular biology in order to present a comprehensive and current view of the neoplastic process. For focus, emphasis is mainly being placed on the neoplastic cells themselves, and not on associated host-mediated responses. It ishoped that this book will accomplish its purpose of providing students and researchers who already possess strong but diverse basic science backgrounds with unifying concepts in tumor pathobiology, so as to stimulate new research aimed at furthering our understanding of neoplastic disease. I wish to express my appreciation and heartfelt thanks to the authors, whose individual ranges of expertise and research experience clearly bring to their respective chapters unique perspectives that easily transcend any redundancy that may be present. In addition, I am grateful to Drs. George Vennart, Saul Kay, and Fred Meier, and to Ms. Connie Wilkerson of the Department of Pathology at MCV, for their helpful comments and their review of some of the material.
- Published
- 2012
16. Animal Tumors of the Female Reproductive Tract : Spontaneous and Experimental
- Author
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E. Cotchin, J. Marchant, E. Cotchin, and J. Marchant
- Subjects
- Generative organs, Female--Cancer, Tumors in animals, Oncology, Experimental, Diseases--Animal models, Animals, Laboratory, Disease models, Animal, Neoplasms, Experimental, Ovarian Neoplasms, Uterine neoplasms
- Abstract
The chapters which comprise this book were prepared as part of a medical text, Pathology of the Female Genital Tract, which is intended for the obstetrician, gynecologist, and medical pathologist. In that context, we were con cerned to bring out the importance of the study of tumors of the female reproductive tract of animals, both as show ing the variety of spontaneous neoplasms that might affect the tract and as providing tumors capable of experimental reproduction. These chapters are published separately, since they contain information which may appeal to a range of readers who might not necessarily wish to acquire the full medical text-for example, to veterinary and comparative pathologists, cancer research workers, research workers in gynecology, experimental pathologists and endocrinologists, and possibly to others using animals in experimental and pharmaceutical studies. The survey of spontaneous tumors of the female repro ductive tract is largely concerned with tumors of the ovaries and uterus of domesticated animals, but attention is also given to laboratory animals, wild animals, and animals in zoos. The spontaneous tumors are well worth studying, not only because of their obvious clinical impor tance to veterinarians, but also because they might provide a stimulus for epidemiologic, etiologic, biologic, and ther apeutic investigations that may elucidate some of the problems related to their counterparts in humans.
- Published
- 2012
17. Fluvastatin sensitizes pancreatic cancer cells toward radiation therapy and suppresses radiation- and/or TGF-β-induced tumor-associated fibrosis
- Author
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Shantibhusan Senapati, Amlan Priyadarshee Mohapatra, Voddu Suresh, Biswajit Das, Deepti Parida, Aliva Prity Minz, Debasish Mohapatra, Rajeeb K. Swain, and Usharani Nayak
- Subjects
Embryo, Nonmammalian ,Cell Survival ,medicine.medical_treatment ,Apoptosis ,Radiation Tolerance ,Pathology and Forensic Medicine ,Mice ,Transforming Growth Factor beta ,In vivo ,Cell Line, Tumor ,Radioresistance ,Pancreatic cancer ,Autophagy ,medicine ,Animals ,Humans ,Fluvastatin ,Molecular Biology ,Cells, Cultured ,Zebrafish ,Chemistry ,Neoplasms, Experimental ,Cell Biology ,medicine.disease ,Fibrosis ,In vitro ,Mice, Inbred C57BL ,Pancreatic Neoplasms ,Radiation therapy ,Cell culture ,NIH 3T3 Cells ,Hepatic stellate cell ,Cancer research ,medicine.drug - Abstract
Pancreatic cancer (PC) is highly resistant to chemo and radiotherapy. Radiation-induced fibrosis (RIF) is a major cause of clinical concern for various malignancies, including PC. In this study, we aimed to evaluate the radiosensitizing and anti-RIF potential of fluvastatin in PC. Short-term viability and clonogenic survival assays were used to evaluate the radiosensitizing potential of fluvastatin in multiple human and murine PC cell lines. The expression of different proteins was analyzed to understand the mechanisms of fluvastatin-mediated radiosensitization of PC cells and its anti-RIF effects in both mouse and human pancreatic stellate cells (PSCs). Finally, these effects of fluvastatin and/or radiation were assessed in an immune-competent syngeneic murine model of PC. Fluvastatin radiosensitized multiple PC cell lines, as well as radioresistant cell lines in vitro, by inhibiting radiation-induced DNA damage repair response. Nonmalignant cells, such as PSCs and NIH3T3 cells, were less sensitive to fluvastatin-mediated radiosensitization than PC cells. Interestingly, fluvastatin suppressed radiation and/or TGF-β-induced activation of PSCs, as well as the fibrogenic properties of these cells in vitro. Fluvastatin considerably augmented the antitumor effect of external radiation therapy and also suppressed intra-tumor RIF in vivo. These findings suggested that along with radiation, fluvastatin co-treatment may be a potential therapeutic approach against PC.
- Published
- 2022
18. Angiogenesis and anti-leukaemia activity of novel indole derivatives as potent colchicine binding site inhibitors
- Author
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Yongfang Yao, Tao Huang, Yuyang Wang, Longfei Wang, Siqi Feng, Weyland Cheng, Longhua Yang, and Yongtao Duan
- Subjects
Models, Molecular ,Indoles ,Angiogenesis Inhibitors ,Antineoplastic Agents ,Apoptosis ,RM1-950 ,Structure-Activity Relationship ,Tubulin ,Cell Line, Tumor ,Drug Discovery ,Animals ,Humans ,Leukaemia ,Zebrafish ,Cell Proliferation ,Pharmacology ,Binding Sites ,Dose-Response Relationship, Drug ,Molecular Structure ,Neovascularization, Pathologic ,Neoplasms, Experimental ,General Medicine ,Tubulin Modulators ,anti-angiogenesis ,Therapeutics. Pharmacology ,Drug Screening Assays, Antitumor ,Colchicine ,Research Article ,Research Paper - Abstract
The screened compound DYT-1 from our in-house library was taken as a lead (inhibiting tubulin polymerisation: IC50=25.6 µM, anti-angiogenesis in Zebrafish: IC50=38.4 µM, anti-proliferation against K562 and Jurkat: IC50=6.2 and 7.9 µM, respectively). Further investigation of medicinal chemistry conditions yielded compound 29e (inhibiting tubulin polymerisation: IC50=4.8 µM and anti-angiogenesis in Zebrafish: IC50=3.6 µM) based on tubulin and zebrafish assays, which displayed noteworthily nanomolar potency against a variety of leukaemia cell lines (IC50= 0.09–1.22 µM), especially K562 cells where apoptosis was induced. Molecular docking, molecular dynamics (MD) simulation, radioligand binding assay and cellular microtubule networks disruption results showed that 29e stably binds to the tubulin colchicine site. 29e significantly inhibited HUVEC tube formation, migration and invasion in vitro. Anti-angiogenesis in vivo was confirmed by zebrafish xenograft. 29e also prominently blocked K562 cell proliferation and metastasis in blood vessels and surrounding tissues of the zebrafish xenograft model. Together with promising physicochemical property and metabolic stability, 29e could be considered an effective anti-angiogenesis and -leukaemia drug candidate that binds to the tubulin colchicine site.
- Published
- 2022
19. Xanthohumol: A Metabolite with Promising Anti-Neoplastic Potential
- Author
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Vaishali Aggarwal, Harpal S. Buttar, Gaurav Parashar, Katrin Sak, Manoj Kumar, Diwakar Aggarwal, Hardeep Singh Tuli, Mehmet Varol, Muobarak J. Tuorkey, and Nidarshana Chaturvedi Parashar
- Subjects
Cancer Research ,Cell cycle checkpoint ,Phytochemicals ,03 medical and health sciences ,Hesperidin ,chemistry.chemical_compound ,0302 clinical medicine ,In vivo ,Neoplasms ,medicine ,Animals ,Humans ,Cell Proliferation ,030304 developmental biology ,Flavonoids ,Pharmacology ,Propiophenones ,0303 health sciences ,Cancer ,Neoplasms, Experimental ,medicine.disease ,Antineoplastic Agents, Phytogenic ,chemistry ,030220 oncology & carcinogenesis ,Apigenin ,Xanthohumol ,Cancer research ,Molecular Medicine ,Emodin ,Kaempferol - Abstract
Abstract: The overwhelming globalburden of cancer has posed numerous challenges and opportunities for developing anti-cancer therapies. Phytochemicalshave emerged as promising synergistic compounds with potential anti-cancer effects to supplement chemo- and immune-therapeutic regimens. Anti cancer synergistic effects have been investigated in the interaction between phytocompounds derived from flavonoids such as quercetin, apigenin, kaempferol, hesperidin, emodin etc., and conventional drugs. Xanthohumol is one of the prenylatedphytoflavonoid that has demonstrated key anti-cancer activities in in vitro (anti proliferation of cancer cell lines) and in vivo(animal models of xenograft tumours)studies, and has been explored from different dimensions for targeting cancer subtypes. In the last decade, xanthohumol has been investigated how it induces the anti-cancer effects at cellular and molecular level.The different signalling cascades and targets of xanthohumolare summarized in thisreview.Overall, this reviewsummarizes the current advances made in the field of natural compounds with special reference to xanthohumol and its promising anti-cancer effectsto inhibit tumour progression.The present review hasalso touched upon the potential of xanthohumol transitioning into a lead candidate from nano-therapy viewpoint along with the challenges which need to be addressed for extensive pre-clinical and clinical anti-cancer studies.
- Published
- 2022
20. Effective Anticancer Therapy by Combination of Nanoparticles Encapsulating Chemotherapeutic Agents and Weak Electric Current
- Author
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Khatun, Anowara, Hasan, Mahadi, El-Emam, Mahran Mohamed Abd, Fukuta, Tatsuya, Mimura, Miyuki, Tashima, Riho, Yoneda, Shintaro, Yoshimi, Shintaro, and Kogure, Kentaro
- Subjects
Male ,Pharmacology ,nanoparticle ,Pharmaceutical Science ,Antineoplastic Agents ,Electrochemical Techniques ,Neoplasms, Experimental ,General Medicine ,Xenograft Model Antitumor Assays ,enhanced permeability and retention effect ,weak electric current ,Mice, Inbred C57BL ,Mice ,Drug Delivery Systems ,Doxorubicin ,Animals ,Nanoparticles ,anticancer therapy ,Melanoma - Abstract
Delivery of medicines using nanoparticles via the enhanced permeability and retention (EPR) effect is a common strategy for anticancer chemotherapy. However, the extensive heterogeneity of tumors affects the applicability of the EPR effect, which needs to overcome for effective anticancer therapy. Previously, we succeeded in the noninvasive transdermal delivery of nanoparticles by weak electric current (WEC) and confirmed that WEC regulates the intercellular junctions in the skin by activating cell signaling pathways (J. Biol. Chem., 289, 2014, Hama et al.). In this study, we applied WEC to tumors and investigated the EPR effect with polyethylene glycol (PEG)-modified doxorubicin (DOX) encapsulated nanoparticles (DOX-NP) administered via intravenous injection into melanoma-bearing mice. The application of WEC resulted in a 2.3-fold higher intratumor accumulation of nanoparticles. WEC decreased the amount of connexin 43 in tumors while increasing its phosphorylation; therefore, the enhancing of intratumor delivery of DOX-NP is likely due to the opening of gap junctions. Furthermore, WEC combined with DOX-NP induced a significant suppression of tumor growth, which was stronger than with DOX-NP alone. In addition, WEC alone showed tumor growth inhibition, although it was not significant compared with non-treated group. These results are the first to demonstrate that effective anticancer therapy by combination of nanoparticles encapsulating chemotherapeutic agents and WEC.
- Published
- 2022
21. Criteria to make animal studies more relevant to treating human cancer
- Author
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Hans Schreiber, Steven P. Wolf, and Frank Wen
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business.industry ,medicine.medical_treatment ,Immunology ,Cancer ,Neoplasms, Experimental ,Bioinformatics ,medicine.disease ,Article ,Mice ,Cancer immunotherapy ,Antigen ,Antigens, Neoplasm ,Neoplasms ,Mutation ,Cancer cell ,medicine ,Animals ,Humans ,Immunology and Allergy ,Malignant cells ,In patient ,Immunotherapy ,Animal studies ,business ,Human cancer - Abstract
Certain aspects of experimental tumor models in mice most accurately reflect the biology and immunology of cancer in patients. A survey of experimental cancer immunotherapy papers published in 2020 shows most do not achieve cancer shrinkage although treatment is initiated at an early time point after cancer cell injection, which does not reflect cancer immunotherapy in patients. Even then, few current experimental approaches eradicate the injected malignant cells, most only delay outgrowth. The value of targeting mutation-encoded tumor-specific antigens becomes increasingly evident while problems of finding normal gene-encoded tumor-associated antigens as safe, effective targets persist. It might be time to refocus on realistic experimental settings and truly cancer-specific targets. These antigens are associated with the least risk of side effects.
- Published
- 2022
22. A Novel Injectable Hydrogel Matrix Loaded With 90Y Microspheres for the Treatment of Solid Tumors
- Author
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Antonino, Amato, Pier Luigi, Carriero, Gordon, McVie, and Giovanni, Paganelli
- Subjects
Male ,Cancer Research ,Neoplasm, Residual ,Antineoplastic Agents ,Hydrogels ,Chemoradiotherapy, Adjuvant ,Neoplasms, Experimental ,General Medicine ,Kidney Neoplasms ,Microspheres ,Injections ,Treatment Outcome ,Oncology ,Animals ,Tissue Distribution ,Yttrium Radioisotopes ,Rabbits - Abstract
The need to concentrate the anti-tumoral activity ofThis in vivo randomized study was planned to assess the efficacy, safety, and biodistribution of BAT-90 in 46 rabbits implanted with a VX2 tumor. The effects of BAT-90 were compared to those ofBAT-90 localized effectively theBAT-90 can be administered as an adjuvant treatment to clear surgical margins from any potential minimal residual disease, or as an alternative to other loco-regional treatments for non-resectable tumors.
- Published
- 2022
23. In Situ Hypoxia-Induced Supramolecular Perylene Diimide Radical Anions in Tumors for Photothermal Therapy with Improved Specificity
- Author
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Hua Wang, Ke-Fei Xue, Yuchong Yang, Hao Hu, Jiang-Fei Xu, and Xi Zhang
- Subjects
Anions ,Macromolecular Substances ,Photothermal Therapy ,Mice, Nude ,Neoplasms, Experimental ,General Chemistry ,Biochemistry ,Catalysis ,Oxygen ,Mice ,Colloid and Surface Chemistry ,Neoplasms ,Animals ,Humans ,Perylene ,HeLa Cells - Abstract
Considering that hypoxia is closely associated with tumor proliferation, invasion, metastasis, and drug resistance, it is of great significance to overcome hypoxia in tumor treatment. Herein, we report a hypoxia-induced specific photothermal therapy (PTT) based on the photothermal agent of supramolecular perylene diimide radical anions. Hypoxic regions in various tumors display strong reductive ability, and in such environments the supramolecular complex of a perylene diimide derivative and cucurbit[7]uril could be reduced to supramolecular perylene diimide radical anions. Benefiting from the strong NIR absorption and good photothermal conversion performance of the in situ generated supramolecular perylene diimide radical anions, the hypoxia-induced PTT strategy exhibits excellent photothermal therapeutic efficiency as well as good specificity and biological safety. Moreover, hypoxia inducible factor expression of tumors decreases to the normal level after PTT treatment. It is anticipated that such a hypoxia-induced specific PTT strategy opens new horizons for photothermal therapy against hypoxic tumors with improved specificity and safety.
- Published
- 2022
24. Polyoxometalate Modified by Zeolite Imidazole Framework for the pH-Responsive Electrodynamic/Chemodynamic Therapy
- Author
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Yan Song, Yuan Sun, Minglu Tang, Zhengya Yue, Jiatong Ni, Junge Zhao, Wenxin Wang, Tiedong Sun, Lianxu Shi, and Lei Wang
- Subjects
Anions ,Mice, Inbred BALB C ,Surface Properties ,Imidazoles ,Antineoplastic Agents ,Biocompatible Materials ,Neoplasms, Experimental ,Hydrogen-Ion Concentration ,Combined Modality Therapy ,Polyelectrolytes ,Mice ,Materials Testing ,Tumor Microenvironment ,Zeolites ,Animals ,Humans ,Female ,General Materials Science ,Drug Screening Assays, Antitumor ,Particle Size ,Reactive Oxygen Species ,Cell Proliferation ,HeLa Cells - Abstract
Electrodynamic therapy (EDT) and chemodynamic therapy (CDT) have the potential for future tumor treatment; however, their underlying applications are greatly hindered owing to their inherent drawbacks. The combination of EDT and CDT has been considered to be an effective way to maximize the superiorities of these two ROS-based methodologies. However, the development of novel nanomaterials with "one-for-all" functions still remains a big challenge. In this work, the polyoxometalate nanoparticles (NPs) were decorated using the zeolite imidazole framework (POM@ZIF-8) in order to integrate the EDT with CDT. The resulting POM@ZIF-8 NPs can effectively induce the generation of reactive oxygen species (ROS)
- Published
- 2022
25. Near-Infrared Upconversion Mesoporous Tin Dioxide Theranostic Nanocapsules for Synergetic Cancer Chemophototherapy
- Author
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Lu Yang, Ruipeng Shi, Ruoxi Zhao, Yanlin Zhu, Bin Liu, Shili Gai, and Lili Feng
- Subjects
Antibiotics, Antineoplastic ,Photosensitizing Agents ,Infrared Rays ,Surface Properties ,Tin Compounds ,Biocompatible Materials ,Mice, Inbred Strains ,Serum Albumin, Bovine ,Neoplasms, Experimental ,Hydrogen-Ion Concentration ,Theranostic Nanomedicine ,Mice ,Nanocapsules ,Doxorubicin ,Materials Testing ,Animals ,Humans ,Female ,General Materials Science ,Drug Screening Assays, Antitumor ,Particle Size ,Porosity ,Cells, Cultured ,Cell Proliferation - Abstract
Smart nanotheranostic systems (SNSs) have attracted extensive attention in antitumor therapy. Nevertheless, constructing SNSs with disease diagnosis ability, improved drug delivery efficiency, inherent imaging performance, and high treatment efficiency remains a scientific challenge. Herein, ultrasmall tin dioxide (SnO
- Published
- 2022
26. Topo II inhibition and DNA intercalation by new phthalazine-based derivatives as potent anticancer agents: design, synthesis, anti-proliferative, docking, and in vivo studies
- Author
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Mohamed M. Khalifa, Ahmed A. Al-Karmalawy, Eslam B. Elkaeed, Mohamed S. Nafie, Mohamed A. Tantawy, Ibrahim H. Eissa, and Hazem A. Mahdy
- Subjects
Antineoplastic Agents ,phthalazine ,RM1-950 ,dna ,intercalators ,Mice ,Structure-Activity Relationship ,antitumer ,Drug Discovery ,Tumor Cells, Cultured ,Animals ,Humans ,Topoisomerase II Inhibitors ,Cell Proliferation ,Pharmacology ,Dose-Response Relationship, Drug ,Molecular Structure ,Neoplasms, Experimental ,General Medicine ,Molecular Docking Simulation ,topo ii ,DNA Topoisomerases, Type II ,Drug Design ,Phthalazines ,Therapeutics. Pharmacology ,Drug Screening Assays, Antitumor ,Research Article ,Research Paper - Abstract
This research presents the design and synthesis of a novel series of phthalazine derivatives as Topo II inhibitors, DNA intercalators, and cytotoxic agents. In vitro testing of the new compounds against HepG-2, MCF-7, and HCT-116 cell lines confirmed their potent cytotoxic activity with low IC50 values. Topo II inhibition and DNA intercalating activities were evaluated for the most cytotoxic members. IC50 values determination demonstrated Topo II inhibitory activities and DNA intercalating affinities of the tested compounds at a micromolar level. Amongst, compound 9d was the most potent member. It inhibited Topo II enzyme at IC50 value of 7.02 ± 0.54 µM with DNA intercalating IC50 of 26.19 ± 1.14 µM. Compound 9d was then subjected to an in vivo antitumor examination. It inhibited tumour proliferation reducing solid tumour volume and mass. Additionally, it restored liver enzymes, proteins, and CBC parameters near-normal, indicating a remarkable amelioration in their functions along with histopathological examinations.
- Published
- 2022
27. Relieving immunosuppression by Endo@PLT targeting anti-angiogenesis to improve the efficacy of immunotherapies
- Author
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Chao, Chen, Yijie, Tang, Hao, Huang, Li, Jia, Lingzi, Feng, Jianya, Zhao, Hao, Zhang, Jian, He, Lingchi, Ding, and Donglin, Xia
- Subjects
Immunosuppression Therapy ,Neovascularization, Pathologic ,Metals and Alloys ,Angiogenesis Inhibitors ,Neoplasms, Experimental ,General Chemistry ,Catalysis ,Surfaces, Coatings and Films ,Electronic, Optical and Magnetic Materials ,Mice, Inbred C57BL ,Mice ,Neoplasms ,Tumor Microenvironment ,Materials Chemistry ,Ceramics and Composites ,Animals ,Humans ,Immunotherapy - Abstract
Low levels of immune infiltrates in the tumor milieu hinder the effectiveness of immunotherapy against immune-cold tumors. In the current work, a tumor-targeting drug delivery system composed of Endo-loaded platelets (Endo@PLT) was developed to relieve immunosuppression by achieving tumor vascular normalization. Endo@PLT reprogrammed the immunostimulatory phenotype, achieving excellent PD-1 immunotherapy
- Published
- 2022
28. Hyperactive neutrophils infiltrate vital organs of tumor bearing host and contribute to gradual systemic deterioration via upregulated NE, MPO and MMP-9 activity
- Author
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Kavita, Rawat, Saima, Syeda, and Anju, Shrivastava
- Subjects
Male ,Mice, Inbred BALB C ,Lymphoma ,Neutrophils ,Immunology ,Cell Growth Processes ,Neoplasms, Experimental ,Neutrophil Activation ,Gene Expression Regulation, Neoplastic ,Mice ,Matrix Metalloproteinase 9 ,Disease Progression ,Animals ,Immunology and Allergy ,Female ,Leukocyte Elastase ,Peroxidase - Abstract
Cancer is known to have systemic impact by targeting various organs that ultimately compromises the overall physiology of the host. Several reports have demonstrated the role of neutrophils in cancer wherein the focus has been drawn on the elevated neutrophil count in blood or at tumor loci. However, their role in mediating systemic effects during cancer progression has not been deciphered so far. Therefore, it is worthwhile to explore whether and how neutrophils contribute to systemic deterioration in cancer. To discern their systemic role, we evaluated neutrophil count and function at different stages of tumor growth in Dalton's Lymphoma mice model. Notably, our results displayed a gradual increase in Ly6G
- Published
- 2022
29. Endogenous cysteine fluorescence monitoring and its deployment in tumour demarcation
- Author
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Yongkang Yue, Tingting Zhao, Kaiqing Ma, Fangjun Huo, and Caixia Yin
- Subjects
Optical Imaging ,Metals and Alloys ,Neoplasms, Experimental ,General Chemistry ,Catalysis ,Surfaces, Coatings and Films ,Electronic, Optical and Magnetic Materials ,Spectrometry, Fluorescence ,Materials Chemistry ,Ceramics and Composites ,Humans ,Cysteine ,Fluorescent Dyes ,HeLa Cells - Abstract
A cysteine-specific fluorescent probe with a wide concentration detection range was used to monitor changes in cysteine levels in HeLa cells under stress and to demarcate the boundary of a xenograft tumour.
- Published
- 2022
30. Nintedanib enhances the efficacy of PD-L1 blockade by upregulating MHC-I and PD-L1 expression in tumor cells
- Author
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Jingyao Tu, Haoran Xu, Li Ma, Chunya Li, Wan Qin, Xinyi Chen, Ming Yi, Li Sun, Bo Liu, and Xianglin Yuan
- Subjects
PD-L1 ,Indoles ,Nintedanib ,Medicine (miscellaneous) ,Cancer immunotherapy ,Idiopathic pulmonary fibrosis ,Antineoplastic Agents ,Apoptosis ,Antibodies ,B7-H1 Antigen ,Interferon-gamma ,Mice ,Cell Line, Tumor ,Antineoplastic Combined Chemotherapy Protocols ,Animals ,Humans ,Neoplasm Metastasis ,Pharmacology, Toxicology and Pharmaceutics (miscellaneous) ,Mice, Inbred BALB C ,Histocompatibility Antigens Class I ,Drug Synergism ,Neoplasms, Experimental ,Up-Regulation ,Mice, Inbred C57BL ,MHC class I ,Drug Screening Assays, Antitumor ,Neoplasm Transplantation ,Research Paper - Abstract
Background: Immune checkpoint inhibitors (ICIs), such as programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1), have been widely applied in clinical and scientific research. Despite their effective antitumor effects in clinical tumor therapy, most tumors are still resistant to ICIs and long-term benefits are lacking. In addition, tumor patients complicated with interstitial lung disease limit the application of ICI therapy. Therefore, for these cases, there is an urgent need to develop new methods to relieve lung complications and enhance the efficacy of ICI therapy. Nintedanib, a potent triple angiokinase inhibitor approved for the treatment of progressive fibrotic interstitial lung disease. However, its immunotherapy synergy properties and mechanism are still pending further exploration. Methods: To explore the therapeutic potential of nintedanib and αPD-L1 combination therapy, MC38, LLC, and 4T1 tumor models were used to investigate antitumor and antimetastatic activities in vivo. An idiopathic pulmonary fibrosis-tumor bearing model was used to evaluate the effect of the synergy therapy on tumor model complicated with lung disease. Moreover, RNA-seq, immunohistochemistry, and flow cytometry were utilized to analyze the effect of combination treatment on the tumor microenvironment. The bioactivity following different treatments was determined by western blotting, CCK-8, and flow cytometry. Results: In this study, nintedanib and αPD-L1 synergy therapy exhibited significant antitumor, antimetastatic and anti-pulmonary fibrosis effects. Both in vitro and in vivo experiments revealed that these effects included promoting vessel normalization, increasing infiltration and activation of immune cells in tumors, enhancing the response of interferon-gamma, and activating the MHC class I-mediated antigen presentation process. Moreover, our results showed an increased expression of PD-L1 and promoted phosphorylation of STAT3 after nintedanib (1 µM) treatment. Conclusion: The combination of nintedanib and αPD-L1 increased ICI therapy responses, relieved lung complications and further activated the tumor immune microenvironment; thus, exhibiting a notable antitumor effect. Accordingly, the nintedanib synergy strategy is expected to be a promising candidate therapy for tumor patients complicated with interstitial lung disease in clinical practice.
- Published
- 2022
31. Circular RNA circ_0000515 adsorbs miR-542-3p to accelerate bladder cancer progression via up-regulating ILK expression
- Author
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Guohui Peng, Jing Guan, Pengfei Leng, Lijun Peng, Manchao Cao, and Yuanfa Feng
- Subjects
Male ,Aging ,Lung Neoplasms ,circ_0000515 ,miR-542-3p ,Mice, Nude ,Cell Biology ,Neoplasms, Experimental ,RNA, Circular ,Middle Aged ,Protein Serine-Threonine Kinases ,Cell Line ,Up-Regulation ,Mice ,MicroRNAs ,Gene Expression Regulation ,Urinary Bladder Neoplasms ,bladder cancer ,Animals ,Humans ,Female ,ILK ,Research Paper ,Cell Proliferation - Abstract
Background: Bladder cancer (BC) is a common cause of cancer-relevant deaths globally. This study is designed to delve into expressions, biological functions and molecular mechanisms of circ_0000515 in BC. Methods: Quantitative real-time polymerase chain reaction was accomplished to examine circ_0000515, miR-542-3p and integrin-linked kinase (ILK) mRNA expressions in BC tissues and cell lines. In RT-4 and RT-112 cells with circ_0000515 depletion and UMUC3 and BIU-87 cells with this circ RNA overexpression, a cell counting kit-8 assay was adopted to monitor the viability. Besides, transwell assay was conducted to detect cell migration and aggressiveness, and luciferase reporter gene assay was applied to probe the interplay among circ_0000515, miR-542-3p and ILK mRNA. Additionally, Besides, the regulatory function of circ_0000515 on miR-542-3p expression was under the assay of quantitative real-time polymerase chain reaction, and western blot was fulfilled to determine the regulative function of circ_0000515/miR-542-3p axis on ILK protein expressions. A xenograft animal was modeled to examine lung metastasis in vivo. Results: Circ_0000515 and ILK expressions were significantly elevated in BC tissues and cell lines, while that of miR-542-3p was dramatically suppressed. Knocking down circ_0000515 could significantly repress the growth, migration and aggressiveness of BC cells while overexpression of circ_0000515 showed opposite effects. Moreover, circ_0000515 knockdown inhibited pulmonary metastasis in vivo. Circ_0000515 was validated to adsorb miR-542-3p, and ILK was testified as the downriver target of miR-542-3p. Circ_0000515 could ascend ILK expression through repressing that of miR-542-3p. Conclusions: Circ_0000515, as a tumor promoter, strengthens the viability, migration and aggressiveness of BC cells via modulating miR-542-3p/ILK axis.
- Published
- 2022
32. Ultrasound Microbubbles Mediated Sonosensitizer and Antibody Co-delivery for Highly Efficient Synergistic Therapy on HER2-Positive Gastric Cancer
- Author
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Lihong Sun, Jinxia Zhang, Menghong Xu, Lulu Zhang, Qingshuang Tang, Jing Chen, Ming Gong, Suhui Sun, Huiyu Ge, Shumin Wang, Xiaolong Liang, and Ligang Cui
- Subjects
Microbubbles ,Receptor, ErbB-2 ,Ultrasonic Therapy ,Mice, Nude ,Biocompatible Materials ,Neoplasms, Experimental ,Trastuzumab ,Antibodies ,Mice ,Antineoplastic Agents, Immunological ,Ultrasonic Waves ,Stomach Neoplasms ,Cell Line, Tumor ,Materials Testing ,Animals ,Humans ,General Materials Science ,Cell Proliferation - Abstract
Trastuzumab combined with chemotherapy is the first-line treatment for advanced HER2-positive gastric cancer, but it still suffers from limited therapeutic efficiency and serious side effects, which are usually due to the poor delivery efficiency and the drug resistance of tumor cells to the chemotherapeutic drugs. Herein, a type of ultrasound microbubble for simultaneous delivery of sonosensitizers and therapeutic antibodies to achieve targeting combination of sonodynamic therapy and antibody therapy of HER2-positive gastric cancer was constructed from pyropheophorbide-lipid followed by trastuzumab conjugation (TP MBs).
- Published
- 2021
33. Understanding CLL biology through mouse models of human genetics
- Author
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Elisa Ten Hacken and Catherine J. Wu
- Subjects
Response to therapy ,Chronic lymphocytic leukemia ,Immunology ,Mice, Transgenic ,Context (language use) ,Review Article ,Disease ,Computational biology ,Biology ,Biochemistry ,Mice ,medicine ,Animals ,Humans ,Human Genetics ,Genomics ,Neoplasms, Experimental ,Cell Biology ,Hematology ,medicine.disease ,Leukemia, Lymphocytic, Chronic, B-Cell ,Human genetics ,Gene Expression Regulation, Neoplastic ,Disease evolution ,Treatment study ,Mutation ,DISEASE TRANSFORMATION ,Neoplasm Transplantation - Abstract
Rapid advances in large-scale next-generation sequencing studies of human samples have progressively defined the highly heterogeneous genetic landscape of chronic lymphocytic leukemia (CLL). At the same time, the numerous challenges posed by the difficulties in rapid manipulation of primary B cells and the paucity of CLL cell lines have limited the ability to interrogate the function of the discovered putative disease “drivers,” defined in human sequencing studies through statistical inference. Mouse models represent a powerful tool to study mechanisms of normal and malignant B-cell biology and for preclinical testing of novel therapeutics. Advances in genetic engineering technologies, including the introduction of conditional knockin/knockout strategies, have opened new opportunities to model genetic lesions in a B-cell–restricted context. These new studies build on the experience of generating the MDR mice, the first example of a genetically faithful CLL model, which recapitulates the most common genomic aberration of human CLL: del(13q). In this review, we describe the application of mouse models to the studies of CLL pathogenesis and disease transformation from an indolent to a high-grade malignancy (ie, Richter syndrome [RS]) and treatment, with a focus on newly developed genetically inspired mouse lines modeling recurrent CLL genetic events. We discuss how these novel mouse models, analyzed using new genomic technologies, allow the dissection of mechanisms of disease evolution and response to therapy with greater depth than previously possible and provide important insight into human CLL and RS pathogenesis and therapeutic vulnerabilities. These models thereby provide valuable platforms for functional genomic analyses and treatment studies.
- Published
- 2021
34. Plasmon-Triggered Upconversion Emissions and Hot Carrier Injection for Combinatorial Photothermal and Photodynamic Cancer Therapy
- Author
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Hong Yuan, Dong Ha Kim, Hyukjin Lee, Filipe Marques Mota, Ru-Shi Liu, Sehoon Kim, Minju Kim, Subin Yu, Dohyub Jang, and Wen-Tse Huang
- Subjects
Materials science ,Cell Survival ,medicine.medical_treatment ,Mice, Nude ,Antineoplastic Agents ,Apoptosis ,Nanotechnology ,Photodynamic therapy ,Lanthanoid Series Elements ,Nanomaterials ,Mice ,Cell Line, Tumor ,Materials Testing ,medicine ,Animals ,Humans ,General Materials Science ,Photosensitizer ,Particle Size ,Surface plasmon resonance ,Plasmon ,Cell Proliferation ,Titanium ,Drug Carriers ,Mice, Inbred BALB C ,Photosensitizing Agents ,Optical Imaging ,Neoplasms, Experimental ,Photothermal therapy ,Photon upconversion ,Photochemotherapy ,Heat generation ,Nanoparticles ,Gold ,Glioblastoma - Abstract
Despite the unique ability of lanthanide-doped upconversion nanoparticles (UCNPs) to convert near-infrared (NIR) light to high-energy UV-vis radiation, low quantum efficiency has rendered their application unpractical in biomedical fields. Here, we report anatase titania-coated plasmonic gold nanorods decorated with UCNPs (Au NR@aTiO2@UCNPs) for combinational photothermal and photodynamic therapy to treat cancer. Our novel architecture employs the incorporation of an anatase titanium dioxide (aTiO2) photosensitizer as a spacer and exploits the localized surface plasmon resonance (LSPR) properties of the Au core. The LSPR-derived near-field enhancement induces a threefold boost of upconversion emissions, which are re-absorbed by neighboring aTiO2 and Au nanocomponents. Photocatalytic experiments strongly infer that LSPR-induced hot electrons are injected into the conduction band of aTiO2, generating reactive oxygen species. As phototherapeutic agents, our hybrid nanostructures show remarkable in vitro anticancer effect under NIR light [28.0% cancer cell viability against Au NR@aTiO2 (77.3%) and UCNP@aTiO2 (98.8%)] ascribed to the efficient radical formation and LSPR-induced heat generation, with cancer cell death primarily following an apoptotic pathway. In vivo animal studies further confirm the tumor suppression ability of Au NR@aTiO2@UCNPs through combinatorial photothermal and photodynamic effect. Our hybrid nanomaterials emerge as excellent multifunctional phototherapy agents, providing a valuable addition to light-triggered cancer treatments in deep tissue.
- Published
- 2021
35. Photoactivation of mitochondrial reactive oxygen species-mediated Src and protein kinase C pathway enhances MHC class II-restricted T cell immunity to tumours
- Author
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Lei Liu, Haocai Chang, Zhengzhi Zou, Jie Li, Xiaorui An, Qi Shen, Sihua Yang, and Da Xing
- Subjects
Cancer Research ,T-Lymphocytes ,Active Transport, Cell Nucleus ,chemical and pharmacologic phenomena ,Mice ,Immune system ,CIITA ,Animals ,STAT1 ,Low-Level Light Therapy ,Antigen-presenting cell ,Protein Kinase C ,Protein kinase C ,Antigen Presentation ,MHC class II ,biology ,Chemistry ,Macrophages ,Histocompatibility Antigens Class II ,Nuclear Proteins ,Dendritic Cells ,Neoplasms, Experimental ,Acquired immune system ,Cell biology ,Mice, Inbred C57BL ,STAT1 Transcription Factor ,src-Family Kinases ,Oncology ,Trans-Activators ,biology.protein ,Reactive Oxygen Species ,Proto-oncogene tyrosine-protein kinase Src - Abstract
High fluence low-level laser (HF-LLL), a mitochondria-targeted tumour phototherapy, results in oxidative damage and apoptosis of tumour cells, as well as damage to normal tissue. To circumvent this, the therapeutic effect of low fluence LLL (LFL), a non-invasive and drug-free therapeutic strategy, was identified for tumours and the underlying molecular mechanisms were investigated. We observed that LFL enhanced antigen-specific immune response of macrophages and dendritic cells by upregulating MHC class II, which was induced by mitochondrial reactive oxygen species (ROS)-activated signalling, suppressing tumour growth in both CD11c-DTR and C57BL/6 mice. Mechanistically, LFL upregulated MHC class II in an MHC class II transactivator (CIITA)-dependent manner. LFL-activated protein kinase C (PKC) promoted the nuclear translocation of CIITA, as inhibition of PKC attenuated the DNA-binding efficiency of CIITA to MHC class II promoter. CIITA mRNA and protein expression also improved after LFL treatment, characterised by direct binding of Src and STAT1, and subsequent activation of STAT1. Notably, scavenging of ROS downregulated LFL-induced Src and PKC activation and antagonised the effects of LFL treatment. Thus, LFL treatment altered the adaptive immune response via the mitochondrial ROS-activated signalling pathway to control the progress of neoplastic disease.
- Published
- 2021
36. Stereotactic body radiation combined with oncolytic vaccinia virus induces potent anti-tumor effect by triggering tumor cell necroptosis and DAMPs
- Author
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Wen-Fang Cheng, Wan-Yu Chen, Bing-Shen Huang, Wei-Zen Sun, Han-Wei Lin, Chi-Fang Chang, and Yu-Li Chen
- Subjects
Cancer Research ,Helper T lymphocyte ,viruses ,medicine.medical_treatment ,Necroptosis ,Vaccinia virus ,CD8-Positive T-Lymphocytes ,Radiosurgery ,Virus ,Mice ,chemistry.chemical_compound ,Immune system ,Cell Line, Tumor ,Tumor Microenvironment ,medicine ,Alarmins ,Animals ,Cytotoxic T cell ,Oncolytic Virotherapy ,business.industry ,Macrophages ,Neoplasms, Experimental ,Immunotherapy ,Combined Modality Therapy ,Oncolytic virus ,Mice, Inbred C57BL ,Oncology ,chemistry ,Cancer research ,Female ,Vaccinia ,business - Abstract
Radiation is an integral part of cancer therapy. With the emergence of oncolytic vaccinia virus immunotherapy, it is important to study the combination of radiation and vaccinia virus in cancer therapy. In this study, we investigated the anti-tumor effect of and immune mechanisms underlying the combination of high-dose hypofractionated stereotactic body radiotherapy (SBRT) and oncolytic vaccinia virus in preclinical murine models. The combination enhanced the in vivo anti-tumor effect and increased the numbers of splenic CD4+Ki-67+ helper T lymphocytes and CD8+Ki-67+ cytotoxic T lymphocytes. Combinational therapy also increased tumor-infiltrating CD3+CD4+ helper T lymphocytes and CD3+CD8+ cytotoxic T lymphocytes, but decreased tumor-infiltrating regulatory T cells. In addition, SBRT combined with oncolytic vaccinia virus enhanced in vitro cell death, partly through necroptosis, and subsequent release of damage-associated molecular patterns (DAMPs), and shifted the macrophage M1/M2 ratio. We concluded that SBRT combined with oncolytic vaccinia virus can trigger tumor cell necroptosis and modify macrophages through the release of DAMPs, and then generate potent anti-tumor immunity and effects. Thus, combined therapy is potentially an important strategy for clinical cancer therapy.
- Published
- 2021
37. A radioenhancing nanoparticle mediated immunoradiation improves survival and generates long-term antitumor immune memory in an anti-PD1-resistant murine lung cancer model
- Author
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Hu, Yun, Paris, Sébastien, Barsoumian, Hampartsoum, Abana, Chike O., He, Kewen, Sezen, Duygu, Wasley, Mark, Masrorpour, Fatemeh, Chen, Dawei, Yang, Liangpeng, Dunn, Joe D., Gandhi, Saumil, Nguyen, Quynh-Nhu, Cortez, Maria Angelica, Welsh, James W., Sezen, Duygu (ORCID 0000-0002-4505-2280 & YÖK ID 170535), Hu, Yun, Paris, Sebastien, Barsoumian, Hampartsoum, Abana, Chike O., He, Kewen, Wasley, Mark, Masrorpour, Fatemeh, Chen, Dawei, Yang, Liangpeng, Dunn, Joe D., Gandhi, Saumil, Nguyen, Quynh-Nhu, Cortez, Maria Angelica, Welsh, James W., and School of Medicine
- Subjects
Radiation-Sensitizing Agents ,Lung Neoplasms ,Biomedical Engineering ,Pharmaceutical Science ,Medicine (miscellaneous) ,Bioengineering ,Applied Microbiology and Biotechnology ,Immune memory ,Mice ,Nanoparticle ,Checkpoint blockade ,Metastatic lung cancer ,Radioimmunotherapy ,NBTXR3 ,Radiation enhancer ,Radiotherapy ,Medical technology ,Animals ,R855-855.5 ,Immune Checkpoint Inhibitors ,Research ,Neoplasms, Experimental ,Biotechnology and applied microbiology ,Nanoscience and nanotechnology ,Science and technology ,Drug Resistance, Neoplasm ,Nanoparticles ,Molecular Medicine ,Female ,Immunologic Memory ,TP248.13-248.65 ,Biotechnology - Abstract
Background: combining radiotherapy with PD1 blockade has had impressive antitumor effects in preclinical models of metastatic lung cancer, although anti-PD1 resistance remains problematic. Here, we report results from a triple-combination therapy in which NBTXR3, a clinically approved nanoparticle radioenhancer, is combined with high-dose radiation (HDXRT) to a primary tumor plus low-dose radiation (LDXRT) to a secondary tumor along with checkpoint blockade in a mouse model of anti-PD1-resistant metastatic lung cancer. Methods: mice were inoculated with 344SQR cells in the right legs on day 0 (primary tumor) and the left legs on day 3 (secondary tumor). Immune checkpoint inhibitors (ICIs), including anti-PD1 (200 mu g) and anti-CTLA4 (100 mu g) were given intraperitoneally. Primary tumors were injected with NBTXR3 on day 6 and irradiated with 12-Gy (HDXRT) on days 7, 8, and 9; secondary tumors were irradiated with 1-Gy (LDXRT) on days 12 and 13. The survivor mice at day 178 were rechallenged with 344SQR cells and tumor growth monitored thereafter. Results: NBTXR3 + HDXRT + LDXRT + ICIs had significant antitumor effects against both primary and secondary tumors, improving the survival rate from 0 to 50%. Immune profiling of the secondary tumors revealed that NBTXR3 + HDXRT + LDXRT increased CD8 T-cell infiltration and decreased the number of regulatory T (Treg) cells. Finally, none of the re-challenged mice developed tumors, and they had higher percentages of CD4 memory T cells and CD4 and CD8 T cells in both blood and spleen relative to untreated mice. Conclusions: NBTXR3 nanoparticle in combination with radioimmunotherapy significantly improves anti-PD1 resistant lung tumor control via promoting antitumor immune response., Cancer Center Support (Core) Grant; Goodwin Family Research Fund; Family of M. Adnan Hamed; Orr Family Foundation; MD Anderson Knowledge Gap Award; Nanobiotix
- Published
- 2021
38. Oligonucleotide conjugated antibody strategies for cyclic immunostaining
- Author
-
Jocelyn A. Jones, Nathan P. McMahon, Ting Zheng, Jennifer Eng, Koei Chin, Sunjong Kwon, Michel A. Nederlof, Joe W. Gray, and Summer L. Gibbs
- Subjects
Multidisciplinary ,Science ,Oligonucleotides ,Fluorescent Antibody Technique ,Mice, Nude ,Molecular imaging ,Neoplasms, Experimental ,Antibodies ,Article ,Mice ,MCF-7 Cells ,Animals ,Humans ,Medicine ,Cancer imaging ,Fluorescent Dyes - Abstract
A number of highly multiplexed immunostaining and imaging methods have advanced spatial proteomics of cancer for improved treatment strategies. While a variety of methods have been developed, the most widely used methods are limited by harmful signal removal techniques, difficulties with reagent production and antigen sensitivity. Multiplexed immunostaining employing oligonucleotide (oligos)-barcoded antibodies is an alternative approach that is growing in popularity. However, challenges remain in consistent conjugation of oligos to antibodies with maintained antigenicity as well as non-destructive, robust and cost-effective signal removal methods. Herein, a variety of oligo conjugation and signal removal methods were evaluated in the development of a robust oligo conjugated antibody cyclic immunofluorescence (Ab-oligo cyCIF) methodology. Both non- and site-specific conjugation strategies were assessed to label antibodies, where site-specific conjugation resulted in higher retained binding affinity and antigen-specific staining. A variety of fluorescence signal removal methods were also evaluated, where incorporation of a photocleavable link (PCL) resulted in full fluorescence signal removal with minimal tissue disruption. In summary, this work resulted in an optimized Ab-oligo cyCIF platform capable of generating high dimensional images to characterize the spatial proteomics of the hallmarks of cancer.
- Published
- 2021
39. Combination therapy with low-frequency ultrasound irradiation and radiofrequency ablation as a synergistic treatment for pancreatic cancer
- Author
-
Tian an Jiang, Hongwei Shi, Haiwei Bao, Wenxiu Ding, Yuting Lu, and Huiyang Wang
- Subjects
low-frequency ultrasound-stimulated microbubbles ,autophagy ,Combination therapy ,Radiofrequency ablation ,Ultrasonic Therapy ,Mice, Nude ,Bioengineering ,Applied Microbiology and Biotechnology ,law.invention ,Mice ,law ,Pancreatic cancer ,Cell Line, Tumor ,Medicine ,Animals ,combined treatment ,Survival rate ,Mice, Inbred BALB C ,Cell growth ,business.industry ,apoptosis ,Cell migration ,General Medicine ,Neoplasms, Experimental ,medicine.disease ,Pancreatic Neoplasms ,surgical procedures, operative ,panc02 cell ,Apoptosis ,Cancer research ,Microbubbles ,radiofrequency ablation ,business ,TP248.13-248.65 ,Research Article ,Research Paper ,Biotechnology - Abstract
We aim to evaluate the efficacies of combination therapy with low-frequency ultrasound-stimulated microbubbles (USMB) and radiofrequency ablation (RFA) on suppressing the proliferation of pancreatic cancer cell and treating Panc02 subcutaneous xenograft mice. The proliferation of HPDE6-C7 and Panc02 cells after the treatment of USMB and RFA alone or combination were evaluated by CCK-8 assay. Scratch test was performed to assess the cell migration capability. Panc02-bearing mice were received 14-day treatment of USMB and RFA alone or combination. Tumor size and survival rate were recorded once two days. The serum levels of immune-related factors and changes of apoptosis- and autophagy-related factors were detected by ELISA and western blotting methods. As a result, CKK-8 assays revealed significant inhibition on Panc02 cell proliferation in combination therapy with USMB and RFA relative to other groups (all p
- Published
- 2021
40. Cardiac myocyte intrinsic contractility and calcium handling deficits underlie heart organ dysfunction in murine cancer cachexia
- Author
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Michelle L, Law and Joseph M, Metzger
- Subjects
Heart Failure ,Male ,Cell biology ,Cachexia ,Multidisciplinary ,Science ,Body Weight ,Cardiology ,Neoplasms, Experimental ,Organ Size ,Myocardial Contraction ,Article ,Mice ,Muscular Atrophy ,Oncology ,Cell Line, Tumor ,Animals ,Humans ,Medicine ,Calcium ,Myocytes, Cardiac ,Cancer - Abstract
Cachexia is a muscle wasting syndrome occurring in many advanced cancer patients. Cachexia significantly increases cancer morbidity and mortality. Cardiac atrophy and contractility deficits have been observed in patients and in animal models with cancer cachexia, which may contribute to cachexia pathophysiology. However, underlying contributors to decreased in vivo cardiac contractility are not well understood. In this study, we sought to distinguish heart-intrinsic changes from systemic factors contributing to cachexia-associated cardiac dysfunction. We hypothesized that isolated heart and cardiac myocyte functional deficits underlie in vivo contractile dysfunction. To test this hypothesis, isolated heart and cardiac myocyte function was measured in the colon-26 adenocarcinoma murine model of cachexia. Ex vivo perfused hearts from cachectic animals exhibited marked contraction and relaxation deficits during basal and pacing conditions. Isolated myocytes displayed significantly decreased peak contraction and relaxation rates, which was accompanied by decreased peak calcium and decay rates. This study uncovers significant organ and cellular-level functional deficits in cachectic hearts outside of the catabolic in vivo environment, which is explained in part by impaired calcium cycling. These data provide insight into physiological mechanisms of cardiomyopathy in cachexia, which is critical for the ultimate development of effective treatments for patients.
- Published
- 2021
41. Hsp90 regulates the tumorigenic function of tyrosine protein kinase in osteosarcoma
- Author
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Zhao-Peng Yao, Dan Gong, Feng Shen, and Hui Zhu
- Subjects
Cell cycle checkpoint ,Carcinogenesis ,Physiology ,Apoptosis ,Biology ,Gene Expression Regulation, Enzymologic ,Mice ,Cell Line, Tumor ,Physiology (medical) ,Heat shock protein ,medicine ,Animals ,Humans ,HSP90 Heat-Shock Proteins ,Protein kinase A ,Pharmacology ,Osteosarcoma ,Neoplasms, Experimental ,Protein-Tyrosine Kinases ,Cell cycle ,medicine.disease ,Hsp90 ,Gene Expression Regulation, Neoplastic ,Cancer cell ,Cancer research ,biology.protein ,Female - Abstract
Despite recent advances in diagnosis and treatment, osteosarcoma remains as the most common bone cancer in children and is associated with poor prognosis. Growing evidence has supported dysregulation of threonine and tyrosine protein kinase (TTK) expression as a hallmark of multiple cancers, however, its function in osteosarcoma remains to be elucidated. In the present study, we found that TTK was frequently overexpressed in osteosarcoma and associated with increased tumor growth and progression. Moreover, using both in vitro and in vivo assays, we provided evidence that TTK level was regulated by a molecular chaperone, heat shock protein 90 (Hsp90). Hsp90 directly interacted with TTK and prevents proteasome-dependent TTK degradation, leading to the accumulation of TTK in osteosarcoma cells. Elevated TTK thus promoted cancer cell proliferation and survival by activating cell cycle progression and inhibiting apoptosis. Consistently, depletion of TTK by Hsp90 inhibition induced cell cycle arrest, generated aneuploidy, and eventually resulted in apoptotic cancer cell death. Together, our study revealed an important Hsp90-TTK regulatory axis in osteosarcoma cells to promote cancer cell growth and survival. These findings expand our knowledge on osteosarcoma pathogenesis and offer novel therapeutic options for clinical practice.
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- 2021
42. Ferroptosis resistance determines high susceptibility of murine A/J strain to iron‐induced renal carcinogenesis
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Kiyoshi Mori, Shinya Toyokuni, Zhen Cheng, Guang Hua Li, Takashi Takahashi, and Shinya Akatsuka
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Male ,Nitrilotriacetic Acid ,Cancer Research ,Carcinogenesis ,SLC7A11 ,GPX4 ,medicine.disease_cause ,Ferric Compounds ,Lipid peroxidation ,Mice ,chemistry.chemical_compound ,iron ,Gene Regulatory Networks ,Sequence Deletion ,Kidney ,biology ,Homozygote ,General Medicine ,animal models ,Kidney Neoplasms ,Up-Regulation ,Gene Expression Regulation, Neoplastic ,medicine.anatomical_structure ,Oncology ,Original Article ,lipocalins ,Injections, Intraperitoneal ,renal cell carcinoma ,Transferrin receptor ,Lipocalin-2 ,Species Specificity ,Receptors, Transferrin ,medicine ,Animals ,Ferroptosis ,Carcinoma, Renal Cell ,Cell damage ,Cyclin-Dependent Kinase Inhibitor p16 ,Cationic Amino Acid Transporter 1 ,Cyclin-Dependent Kinase Inhibitor p15 ,Original Articles ,Neoplasms, Experimental ,medicine.disease ,Molecular biology ,Ferritin ,Oxidative Stress ,chemistry ,Ferritins ,biology.protein ,Lipid Peroxidation - Abstract
Cancer susceptibility is a critical factor in the understanding of carcinogenesis. Intraperitoneal (i.p.) injection of an iron chelate, ferric nitrilotriacetate (Fe‐NTA), produces hydroxyl radicals via Fenton reaction to induce ferroptosis in renal proximal tubules. Rats or mice subjected to repeated i.p. injections of Fe‐NTA develop renal cell carcinoma (RCC). To elucidate the molecular mechanisms that cause susceptibility to renal carcinogenesis, we first established an inter‐strain difference in the susceptibility to Fe‐NTA‐induced renal carcinogenesis in mice. Based on a previous observation of a low incidence of RCC with this model in C57BL/6J strain mice, we investigated A/J strain mice here, which demonstrated significantly higher susceptibility to Fe‐NTA‐induced renal carcinogenesis. Homozygous deletion of the Cdkn2a/2b tumor suppressor locus was detected for the first time in A/J strain mice. Focusing on ferroptosis and iron metabolism, we explored the mechanisms involved that lead to the difference in RCC development. We compared the protective responses in the kidney of A/J and C57BL/6J strains after Fe‐NTA treatment. After 3‐week Fe‐NTA treatment, A/J mice maintained higher levels of expression of glutathione peroxidase 4 and xCT (SLC7A11), leading to a lower level of lipid peroxidation. Simultaneously, A/J mice had decreased expression of transferrin receptor and increased expression of ferritin to greater degrees than C57BL/6 mice. After a single Fe‐NTA injection, higher levels of oxidative cell damage and cytosolic catalytic Fe(II) were observed in C57BL/6J mice, accompanied by a greater increase in lipocalin‐2. Lipocalin‐2 deficiency significantly decreased oxidative renal damage. Our results suggest that a genetic trait favoring ferroptosis resistance contributes to high susceptibility to Fe‐NTA‐induced RCC in A/J strain., Cancer susceptibility is an important issue when considering cancer prevention. In this paper, we used an iron‐mediated oxidative stress‐induced renal carcinogenesis model in mice and found that ferroptosis resistance is an important factor determining cancer susceptibility.
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- 2021
43. Biodegradable Hollow Polydopamine@manganese Dioxide as an Oxygen Self-Supplied Nanoplatform for Boosting Chemo-photodynamic Cancer Therapy
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Lu Liu, Wen-Bo Wang, Wei Xue, Dong Ma, Haiyang Wang, Li Guowei, Meng Wang, Siming Yu, Bo Li, and Hang Li
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Indoles ,Materials science ,Cell Survival ,Polymers ,medicine.medical_treatment ,Mice, Nude ,Nanoparticle ,Apoptosis ,Photodynamic therapy ,Mice ,chemistry.chemical_compound ,Biomimetic Materials ,Cell Line, Tumor ,Materials Testing ,PEG ratio ,polycyclic compounds ,medicine ,Animals ,General Materials Science ,Photosensitizer ,Doxorubicin ,Particle Size ,Cell Proliferation ,Mice, Inbred BALB C ,Tumor microenvironment ,Antibiotics, Antineoplastic ,Tumor hypoxia ,Oxides ,Neoplasms, Experimental ,Combinatorial chemistry ,Oxygen ,Drug Liberation ,Manganese Compounds ,Photochemotherapy ,chemistry ,Nanoparticles ,Tumor Hypoxia ,Female ,Drug Screening Assays, Antitumor ,Porosity ,Ethylene glycol ,medicine.drug - Abstract
Photodynamic therapy (PDT) has attracted extensive attention in the clinical treatment of malignant tumor. However, the acidic and hypoxic conditions of the tumor microenvironment (TME) limit the further application of PDT in the clinic. Herein, we fabricate a new nanoplatform─HPDA@MnO2@Ce6/DOX@PEG-RGD (HPMRCD)─by means of coating hollow polydopamine nanoparticles (HPDA) with manganese dioxide (MnO2), which is modified by cyclic RGD functionalized poly(ethylene glycol) (PEG) and further co-loaded with a photosensitizer, Chlorin e6 (Ce6), and a chemotherapy drug, doxorubicin (DOX). This nanoplatform could be enriched in tumor tissues, then instantly dissociated under an acidic and H2O2-rich TME. The dual-responsive release of Mn2+ ions and oxygen (O2) can relieve tumor hypoxia, which can be used as a magnetic resonance contrast agent and the latter can enhance the PDT effect. Furthermore, the degradation of HPMRCD leads to an efficient loaded therapeutic molecule release, thus yielding a potential therapy to enhance tumor suppression by adopting the combined chemo-photodynamic therapy.
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- 2021
44. Stable Loading and Delivery of Melittin with Lipid-Coated Polymeric Nanoparticles for Effective Tumor Therapy with Negligible Systemic Toxicity
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Yuan Zheng, Yuetan Chen, Wanxin Zhu, Xiaohui Wei, Sanyuan Shi, Liuxin Yang, Yang Chen, Ran Ye, Yuhong Xu, Jinliang Peng, and Anqi Wang
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Materials science ,Surface Properties ,Mice, Nude ,Antineoplastic Agents ,Polyethylene glycol ,Hemolysis ,Melittin ,Polyethylene Glycols ,Mice ,chemistry.chemical_compound ,Coated Materials, Biocompatible ,In vivo ,PEG ratio ,medicine ,Animals ,Humans ,General Materials Science ,Particle Size ,Cytotoxicity ,Lipid bilayer ,Cell Proliferation ,Drug Carriers ,technology, industry, and agriculture ,Neoplasms, Experimental ,medicine.disease ,Lipids ,Melitten ,chemistry ,A549 Cells ,Biophysics ,Systemic administration ,Nanoparticles ,Female ,Drug Screening Assays, Antitumor - Abstract
Melittin is a potential anticancer candidate with remarkable antitumor activity and ability to overcome tumor drug resistance. However, the clinical applications of melittin are largely restricted by its severe hemolytic activity and nonspecific cytotoxicity after systemic administration. Here, a biocompatible and stable melittin-loaded lipid-coated polymeric nanoparticle (MpG@LPN) formulation that contains a melittin/poly-γ-glutamic acid nanoparticle inner core, a lipid membrane middle layer, and a polyethylene glycol (PEG) and PEG-targeting molecule outer shell was designed. The formulations were prepared by applying a self-assembly procedure based on intermolecular interactions, including electrostatic attraction and hydrophobic effect. The core-shell MpG@LPN presented high efficiency for melittin encapsulation and high stability in physiological conditions. Hemolysis and cell proliferation assays showed that the PEG-modified MpG@LPN had almost no hemolytic activity and nonspecific cytotoxicity even at high concentrations. The modification of targeting molecules on the MpG@LPNs allowed for the selective binding with target tumor cells and cytolytic activity via apoptosis induction. In vivo experiments revealed that MpG@LPNs can remarkably inhibit the growth of tumors without the occurrence of hemolysis and tissue toxicity. Results suggested that the developed MpG@LPN with a core-shell structure can effectively address the main obstacles of melittin in clinical applications and has great potential in cancer treatment.
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- 2021
45. In Situ Nanotransformable Hydrogel for Chemo-Photothermal Therapy of Localized Tumors and Targeted Therapy of Highly Metastatic Tumors
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Veeresh B, Aravind Kumar Rengan, Syed Baseeruddin Alvi, Rajalakshmi P S, Anil Jogdand, and Nazia Begum
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Lung Neoplasms ,Materials science ,Palliative care ,Photothermal Therapy ,Surface Properties ,Injections, Subcutaneous ,medicine.medical_treatment ,Melanoma, Experimental ,Biocompatible Materials ,Cell Line ,Metastasis ,Targeted therapy ,Mice ,In vivo ,medicine ,Animals ,General Materials Science ,Particle Size ,Mice, Inbred BALB C ,Chemotherapy ,Antibiotics, Antineoplastic ,Melanoma ,technology, industry, and agriculture ,Hydrogels ,Neoplasms, Experimental ,Photothermal therapy ,medicine.disease ,Mice, Inbred C57BL ,Doxorubicin ,Liposomes ,Self-healing hydrogels ,Cancer research ,Nanoparticles ,Female ,Gold - Abstract
Metastasis is one of the predisposing factors for cancer-related mortalities worldwide. Patients with advanced cancers (stage IV) receive palliative care with minimal possibility of achieving complete remission. Antibody-based therapeutic modalities are capable of targeting tumors that are confined to a particular location but are ineffective in targeting distant secondary tumors. In the current study, we have developed a smart nano-transforming hydrogel (NTG) that transforms in situ to polymeric nanoparticles (PA NPs) of 100-150 nm when injected subcutaneously. These nanoparticles targeted the primary and secondary metastatic tumors for up to ∼5 and ∼3 days, respectively. The in situ-formed PA NPs also demonstrated a pH-responsive drug release resulting in about ∼80% release within 100 h at 5.8 pH. When tested in vivo, substantial inhibition of lung metastases was observed compared to chemotherapy, thus demonstrating the efficiency of nanotransforming hydrogels in targeting and inhibiting primary and secondary metastatic tumors.
- Published
- 2021
46. NIR-II Fluorophore with Dithienylethene as an Electron Donor for Fluorescence/Photoacoustic Dual-Model Imaging and Photothermal Therapy
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Xiqun Jiang, Quli Fan, Xin Wang, Shuo Yang, Panpan Xiao, Ruonan Wang, Wei Wu, Jia Li, and Ying Sun
- Subjects
Fluorescence-lifetime imaging microscopy ,Fluorophore ,Materials science ,Infrared Rays ,Photothermal Therapy ,Surface Properties ,Electron donor ,Thiophenes ,Conjugated system ,Fluorescence ,Photoacoustic Techniques ,Mice ,chemistry.chemical_compound ,Photochromism ,Animals ,Humans ,General Materials Science ,Particle Size ,Density Functional Theory ,Micelles ,Fluorescent Dyes ,chemistry.chemical_classification ,Molecular Structure ,business.industry ,Optical Imaging ,Neoplasms, Experimental ,Photothermal therapy ,Electron acceptor ,chemistry ,Optoelectronics ,business - Abstract
Well-designed second near-infrared (NIR-II) fluorophores are promising in optical diagnosis and therapy of tumors. In this work, we synthesized a donor-acceptor-donor (D-A-D) NIR-II fluorophore named BBTD-BET with dithienylethene as an electron donor and benzobisthiadiazole as an electron acceptor. To the best of our knowledge, this is the first report of using dithienylethene, a typical photochromic molecule, as a building block for NIR-II fluorophores. We studied the geometrical configuration, electronic state, and optical properties of BBTD-BET by both theoretical and experimental means. BBTD-BET had absorption and emission in the NIR-I and NIR-II spectral ranges, respectively. Using PEGylated BBTD-BET as a theranostic agent, we achieved NIR-II fluorescence/photoacoustic (PA) dual-modal imaging and attained high imaging resolution, desired signal-to-noise ratio, and excellent photothermal therapy (PTT) efficacy. After one PTT treatment, the tumors established in mice were eradicated. This work provides a novel organic conjugated molecule integrating NIR-II/PA dual-modal imaging and PTT functionalities that is very promising in the theranostic of tumors.
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- 2021
47. Yolk–Shell-Type Gold Nanoaggregates for Chemo- and Photothermal Combination Therapy for Drug-Resistant Cancers
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Jae Ho Kim, Seong Gyu Kwon, Min Joo Shin, Dae Kyoung Kim, Hyun-Seok Choe, Jae-Hyuk Kim, Kyung Un Choi, and Hak-Lae Lee
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Male ,Materials science ,Biocompatibility ,Photothermal Therapy ,Surface Properties ,Metal Nanoparticles ,Mice, Nude ,Mice ,In vivo ,Tumor Cells, Cultured ,medicine ,Animals ,Humans ,General Materials Science ,Doxorubicin ,Particle Size ,Cell Proliferation ,Ovarian Neoplasms ,Mice, Inbred BALB C ,Antibiotics, Antineoplastic ,Cell Death ,Photothermal effect ,Neoplasms, Experimental ,Photothermal therapy ,medicine.disease ,Mesoporous organosilica ,Drug Resistance, Neoplasm ,Cancer cell ,Cancer research ,Female ,Gold ,Drug Screening Assays, Antitumor ,Ovarian cancer ,medicine.drug - Abstract
Epithelial ovarian cancer is a gynecological cancer with the highest mortality rate, and it exhibits resistance to conventional drugs. Gold nanospheres have gained increasing attention over the years as photothermal therapeutic nanoparticles, owing to their excellent biocompatibility, chemical stability, and ease of synthesis; however, their practical application has been hampered by their low colloidal stability and photothermal effects. In the present study, we developed a yolk-shell-structured silica nanocapsule encapsulating aggregated gold nanospheres (aAuYSs) and examined the photothermal effects of aAuYSs on cell death in drug-resistant ovarian cancers both in vitro and in vivo. The aAuYSs were synthesized using stepwise silica seed synthesis, surface amino functionalization, gold nanosphere decoration, mesoporous organosilica coating, and selective etching of the silica template. Gold nanospheres were agglomerated in the confined silica interior of aAuYSs, resulting in the red-shifting of absorbance and enhancement of the photothermal effect under 808 nm laser irradiation. The efficiency of photothermal therapy was first evaluated by inducing aAuYS-mediated cell death in A2780 ovarian cancer cells, which were cultured in a two-dimensional culture and a three-dimensional spheroid culture. We observed that photothermal therapy using aAuYSs together with doxorubicin treatment synergistically induced the cell death of doxorubicin-resistant A2780 cancer cells in vitro. Furthermore, this type of combinatorial treatment with photothermal therapy and doxorubicin synergistically inhibited the in vivo tumor growth of doxorubicin-resistant A2780 cancer cells in a xenograft transplantation model. These results suggest that photothermal therapy using aAuYSs is highly effective in the treatment of drug-resistant cancers.
- Published
- 2021
48. Pillar[6]arene-Based Supramolecular Nanocatalysts for Synergistically Enhanced Chemodynamic Therapy by the Intracellular Cascade Reaction
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Peng Zhu, Liu Xin, Chi Meng, Xiao Liu, Shijia Ling, Yanan Zhang, Ji Liu, Yong Ling, and Jianqiang Qian
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Materials science ,Biocompatibility ,Cell Survival ,Macromolecular Substances ,Metallocenes ,Photothermal Therapy ,Mice, Nude ,Antineoplastic Agents ,Catalysis ,Mice ,chemistry.chemical_compound ,Cascade reaction ,medicine ,Animals ,Humans ,General Materials Science ,Particle Size ,Hydrogen peroxide ,Hydroxyl Radical ,Neoplasms, Experimental ,Hydrogen-Ion Concentration ,Prodrug ,Combinatorial chemistry ,Nanomaterial-based catalyst ,Quaternary Ammonium Compounds ,Glucose ,chemistry ,Cancer cell ,Nanoparticles ,Drug Screening Assays, Antitumor ,HT29 Cells ,Camptothecin ,Intracellular ,medicine.drug - Abstract
Chemodynamic therapy (CDT) based on the intracellular Fenton reaction has become increasingly explored in cancer treatment. However, the mildly acidic tumor microenvironment and the limited amount of intracellular hydrogen peroxide (H2O2) will create issues for CDT to perform a sustained and high-efficiency treatment. Therefore, how to selectively reduce the pH value and augment the amount of H2O2 in tumor tissues has become the key factor for realizing excellent CDT. Besides, the majority of the reported CDT systems have been constructed from iron-based inorganic or metal-organic framework nanomaterials due to the decisive role of metals in CDT, which restricts the development of CDT. In this study, inspired by the host-guest interactions between pillar[6]arene and ferrocene, a ternary pillar[6]arene-based supramolecular nanocatalyst (GOx@T-NPs) for CDT is reported for the first time. GOx@T-NPs not only exhibited a high-efficiency catalytic ability to convert glucose into hydroxyl radicals (•OH) and to reduce the pH value inside cancer cells for significant enhancement of the CDT effect, but they also showed sensitive glutathione-induced camptothecin (CPT) prodrug release capacity for further improving the efficiency of CDT. Hence, GOx@NPs possessed excellent ability to synergistically enhance the CDT. Additionally, an antitumor mechanism study showed that the prominent tumor inhibition capacity of GOx@T-NPs was derived from trimodal synergistic interactions of CDT, starvation therapy, and chemotherapy. Moreover, GOx@T-NPs manifested good biocompatibility and tumor selectivity with few side effects in major organs. This work broadens the range of materials available for CDT and demonstrates new developments in pillar[n]arene-based multimodal synergistic treatment systems.
- Published
- 2021
49. The Effect of Metformin on the Proliferation, Apoptosis and CD133 mRNA Expression of Colon Cancer Stem Cells by Upregulation of miR 342-3p
- Author
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Mingwei Chen, Zongwen Shuai, Lili Deng, Yaqin Zhang, and Ruofei Chen
- Subjects
Male ,colon cancer stem cells ,Mice, Nude ,Pharmaceutical Science ,Apoptosis ,Flow cytometry ,Mice ,Downregulation and upregulation ,Cell Line, Tumor ,Drug Discovery ,microRNA ,medicine ,Animals ,Humans ,CD133 ,AC133 Antigen ,RNA, Messenger ,Viability assay ,neoplasms ,Original Research ,Cell Proliferation ,Pharmacology ,Messenger RNA ,medicine.diagnostic_test ,business.industry ,Neoplasms, Experimental ,Transfection ,tumor suppressor-related miRNAs ,Metformin ,Up-Regulation ,carbohydrates (lipids) ,MicroRNAs ,Colonic Neoplasms ,embryonic structures ,Neoplastic Stem Cells ,Cancer research ,biological phenomena, cell phenomena, and immunity ,Stem cell ,business - Abstract
Objective To explore whether metformin (MET) can affect the biological behaviour and CD133 mRNA expression of CD133+ colon cancer stem cells (CCSCs) through miR-342-3p. Methods The direct immunomagnetic bead method was used to select CD133+ CCSCs from the SW480 and HCT116 cell lines, and miRNA-tailing qRT-PCR was used to detect the expression changes of tumor suppressor-related miRNAs (miR-34a, miR-126, miR-143, miR-145, miR-342-3p, miR-342-5p) after MET intervention. Then, miR-342-3p with markedly significant differential expression was selected as the target miRNA. The lentiviruses LV16-hsa-miR-342-3p inhibitor and LV16-NC were used for the transfection inhibition test. CCK-8, flow cytometry, and qRT-PCR were used to detect the cell viability, apoptosis rate, and CD133 mRNA expression of CD133+ CCSCs. Results Under the high-glucose environment, the expression of tumor suppressor-related miRNAs in CCSCs changed differently (p 0.05), but the expression of CD133 mRNA markedly increased (p
- Published
- 2021
50. In Vitro and In Vivo of Triphenylamine-Appended Fluorescent Half-Sandwich Iridium(III) Thiosemicarbazones Antitumor Complexes
- Author
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Jinghang Guo, Chao Gao, Jiawen Zong, Weiyan Liu, Mingxiao Shao, Zhe Liu, Xicheng Liu, Xinzhuo Sun, and Meimei Yao
- Subjects
Thiosemicarbazones ,Cell Survival ,Mice, Nude ,chemistry.chemical_element ,Antineoplastic Agents ,Apoptosis ,Iridium ,Triphenylamine ,Inorganic Chemistry ,Mice ,chemistry.chemical_compound ,Coordination Complexes ,In vivo ,medicine ,Animals ,Humans ,Physical and Theoretical Chemistry ,Semicarbazone ,Cell Proliferation ,Fluorescent Dyes ,Cisplatin ,Mice, Inbred BALB C ,Aniline Compounds ,Dose-Response Relationship, Drug ,Molecular Structure ,Neoplasms, Experimental ,Cell cycle ,Enol ,Combinatorial chemistry ,In vitro ,chemistry ,A549 Cells ,Drug Screening Assays, Antitumor ,Reactive Oxygen Species ,medicine.drug - Abstract
Half-sandwiched structure iridium(III) complexes appear to be an attractive organometallic antitumor agents in recent years. Here, four triphenylamine-modified fluorescent half-sandwich iridium(III) thiosemicarbazone (TSC) antitumor complexes were developed. Because of the "enol" configuration of the TSC ligands, these complexes formed a unique dimeric configuration. Aided by the appropriate fluorescence properties, studies found that complexes could enter tumor cells in an energy-dependent mode, accumulate in lysosomes, and result in the damage of lysosome integrity. Complexes could block the cell cycle, improve the levels of intrastitial reactive oxygen species, and lead to apoptosis, which followed an antitumor mechanism of oxidation. Compared with cisplatin, the antitumor potential in vivo and vitro confirmed that Ir4 could effectively inhibit tumor growth. Meanwhile, Ir4 could avoid detectable side effects in the experiments of safety evaluation. Above all, half-sandwich iridium(III) TSC complexes are expected to be an encouraging candidate for the treatment of malignant tumors.
- Published
- 2021
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