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Deng H, Eichmann A, Schwartz MA. Fluid Shear Stress-Regulated Vascular Remodeling: Past, Present, and Future. Arterioscler Thromb Vasc Biol 2025; 45:882-900. [PMID: 40207366 DOI: 10.1161/atvbaha.125.322557] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/11/2025]
Abstract
The vascular system remodels throughout life to ensure adequate perfusion of tissues as they grow, regress, or change metabolic activity. Angiogenesis, the sprouting of new blood vessels to expand the capillary network, versus regression, in which endothelial cells die or migrate away to remove unneeded capillaries, controls capillary density. In addition, upstream arteries adjust their diameters to optimize blood flow to downstream vascular beds, which is controlled primarily by vascular endothelial cells sensing fluid shear stress (FSS) from blood flow. Changes in capillary density and small artery tone lead to changes in the resistance of the vascular bed, which leads to changes in flow through the arteries that feed these small vessels. The resultant decreases or increases in FSS through these vessels then stimulate their inward or outward remodeling, respectively. This review summarizes our knowledge of endothelial FSS-dependent vascular remodeling, offering insights into potential therapeutic interventions. We first provide a historical overview, then discuss the concept of set point and mechanisms of low-FSS-mediated and high-FSS-mediated inward and outward remodeling. We then cover in vivo animal models, molecular mechanisms, and clinical implications. Understanding the mechanisms underlying physiological endothelial FSS-mediated vascular remodeling and their failure due to mutations or chronic inflammatory and metabolic stresses may lead to new therapeutic strategies to prevent or treat vascular diseases.
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Affiliation(s)
- Hanqiang Deng
- Yale Cardiovascular Research Center CT (H.D., A.E., M.A.S.), Yale University School of Medicine, New Haven, CT
- Section of Cardiovascular Medicine, Department of Internal Medicine (H.D., A.E., M.A.S.), Yale University School of Medicine, New Haven, CT
| | - Anne Eichmann
- Yale Cardiovascular Research Center CT (H.D., A.E., M.A.S.), Yale University School of Medicine, New Haven, CT
- Section of Cardiovascular Medicine, Department of Internal Medicine (H.D., A.E., M.A.S.), Yale University School of Medicine, New Haven, CT
| | - Martin A Schwartz
- Yale Cardiovascular Research Center CT (H.D., A.E., M.A.S.), Yale University School of Medicine, New Haven, CT
- Section of Cardiovascular Medicine, Department of Internal Medicine (H.D., A.E., M.A.S.), Yale University School of Medicine, New Haven, CT
- Department of Cell Biology, Yale School of Medicine, New Haven, CT (M.A.S.)
- Department of Biomedical Engineering, Yale School of Engineering, New Haven, CT (M.A.S.)
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2
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Gao S, Gao S, Wang Y, Xiang L, Peng H, Chen G, Xu J, Zhang Q, Zhu C, Zhou Y, Li N, Shen X. Inhibition of Vascular Endothelial Growth Factor Reduces Photoreceptor Death in Retinal Neovascular Disease via Neurotrophic Modulation in Müller Glia. Mol Neurobiol 2025; 62:6352-6368. [PMID: 39789237 DOI: 10.1007/s12035-025-04689-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2023] [Accepted: 01/02/2025] [Indexed: 01/12/2025]
Abstract
VEGF is not only the most potent angiogenic factor, but also an important neurotrophic factor. In this study, vitreous expression of six neurotrophic factors were examined in proliferative diabetic retinopathy (PDR) patients with prior anti-VEGF therapy (n = 48) or without anti-VEGF treatment (n = 41) via ELISA. Potential source, variation and impact of these factors were further investigated in a mouse model of oxygen-induced retinopathy (OIR), as well as primary Müller cells and 661W photoreceptor cell line under hypoxic condition. Results showed that vitreous levels of NGF, NT-3, NT-4, BDNF, GDNF and CNTF were significantly higher in eyes undergoing anti-VEGF therapy compared with PDR controls. Statistical correlation between vitreous VEGF and each trophic factor was found. Hypoxia significantly induced the expressions of these neurotrophic factors, whereas application of anti-VEGF agent in OIR model could further upregulate retinal NGF, NT-3, NT-4, together with downregulation of BDNF, GDNF, CNTF, especially in Müller glia. Inhibition of Müller cell-derived VEGF would result in similar neurotrophic changes under hypoxia. With changes of corresponding neurotrophic receptors in the cocultured photoreceptor cells, their synergic effect could protect hypoxic photoreceptor from apoptosis when VEGF inhibition was present. These findings demonstrated that regulation of Müller cell-derived neurotrophic factors might be one of the possible mechanisms by which anti-VEGF therapy produced neuroprotective effects on PDR. These results provided new evidence for the therapeutic strategy of PDR.
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Affiliation(s)
- Shuang Gao
- Department of Ophthalmology, Ruijin Hospital, Affiliated Shanghai Jiaotong University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, China
| | - Sha Gao
- Department of Ophthalmology, Ruijin Hospital, Affiliated Shanghai Jiaotong University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, China
| | - Yanuo Wang
- Department of Ophthalmology, Ruijin Hospital, Affiliated Shanghai Jiaotong University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, China
| | - Lu Xiang
- Department of Ophthalmology, Ruijin Hospital, Affiliated Shanghai Jiaotong University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, China
| | - Hanwei Peng
- Department of Ophthalmology, Ruijin Hospital, Affiliated Shanghai Jiaotong University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, China
| | - Gong Chen
- Department of Ophthalmology, Ruijin Hospital, Affiliated Shanghai Jiaotong University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, China
| | - Jianmin Xu
- Department of Ophthalmology, Ruijin Hospital, Affiliated Shanghai Jiaotong University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, China
| | - Qiong Zhang
- Department of Ophthalmology, Ruijin Hospital, Affiliated Shanghai Jiaotong University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, China
| | - Caihong Zhu
- Department of Ophthalmology, Ruijin Hospital, Affiliated Shanghai Jiaotong University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, China
| | - Yingming Zhou
- Department of Ophthalmology, Ruijin Hospital, Affiliated Shanghai Jiaotong University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, China
| | - Na Li
- Department of Ophthalmology, Ruijin Hospital, Affiliated Shanghai Jiaotong University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, China.
| | - Xi Shen
- Department of Ophthalmology, Ruijin Hospital, Affiliated Shanghai Jiaotong University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, China.
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Zhong X, Fei Y, Zhao H, Chen J, Gao M, Huang Y, Fei W. Mechanistic studies and therapeutic potential of angiopoietin in head and neck tumor angiogenesis. Front Oncol 2025; 15:1529225. [PMID: 40260291 PMCID: PMC12010120 DOI: 10.3389/fonc.2025.1529225] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2024] [Accepted: 02/21/2025] [Indexed: 04/23/2025] Open
Abstract
Head and neck tumors represent a prevalent category of oral and maxillofacial malignancies, posing significant therapeutic and prognostic challenges due to their complex anatomical structure, tumor heterogeneity, and resistance to conventional therapies. Recent studies have highlighted the strong association between tumor progression and neoangiogenesis, with the angiopoietin (ANG) family playing a central role in this process. Comprising ANG1, ANG2, ANG3, and ANG4, these factors regulate multiple signaling pathways that promote cellular growth, differentiation, and proliferation, thereby driving angiogenesis and accelerating tumor growth and metastasis. Therefore, a comprehensive investigation of the ANG family's role in head and neck tumors may offer critical insights into tumorigenesis mechanisms and unveil novel therapeutic targets. Such research has the potential to improve treatment outcomes and enhance the quality of life for patients.
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Affiliation(s)
- Xiaojuan Zhong
- School of Medicine, University of Electronic Science and Technology, Chengdu, Sichuan, China
| | - Yujie Fei
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China
| | - Haihui Zhao
- School of Stomatology, Southwest Medical University, Luzhou, Sichuan, China
| | - Jiao Chen
- State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China
| | - Mingyu Gao
- Yibin Second People’s Hospital, Yibin, Sichuan, China
| | - Yi Huang
- Department of Maxillofacial Surgery, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Wei Fei
- Department of Maxillofacial Surgery, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
- Department of Oral and Maxillofacial Surgery, Wenjiang Hospital, Sichuan Provincial People’s Hospital, Chengdu, Sichuan, China
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Loh WW, Lin Q, Zhao X, Su X, Loh XJ, Lim JYC. Polyurea-urethane Temperature-responsive Hydrogels for Sustained Delivery of Anti-VEGF Therapeutics. Chem Asian J 2024; 19:e202400453. [PMID: 38878271 DOI: 10.1002/asia.202400453] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2024] [Revised: 06/09/2024] [Indexed: 07/26/2024]
Abstract
Temperature-responsive hydrogels, or thermogels, have emerged as a leading platform for sustained delivery of both small molecule drugs and macromolecular biologic therapeutics. Although thermogel properties can be modulated by varying the polymer's hydrophilic-hydrophobic balance, molecular weight and degree of branching, varying the supramolecular donor-acceptor interactions on the polymer remains surprisingly overlooked. Herein, to study the influence of enhanced hydrogen bonding on thermogelation, we synthesized a family of amphiphilic polymers containing urea and urethane linkages using quinuclidine as an organocatalyst. Our findings showed that the presence of strongly hydrogen bonding urea linkages significantly enhanced polymer hydration in water, in turn affecting hierarchical polymer self-assembly and macroscopic gel properties such as sol-gel phase transition temperature and gel stiffness. Additionally, analysis of the sustained release profiles of Aflibercept, an FDA-approved protein biologic for anti-angiogenic treatment, showed that urea bonds on the thermogel were able to significantly alter the drug release mechanism and kinetics compared to usage of polyurethane gels of similar composition and molecular weight. Our findings demonstrate the unrealized possibility of modulating gel properties and outcomes of sustained drug delivery through judicious variation of hydrogen bonding motifs on the polymer structure.
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Affiliation(s)
- Wei Wei Loh
- Institute of Materials Research and Engineering (IMRE), Agency for Science, Technology and Research (A*STAR) #08-03, 2 Fusionopolis Way, Singapore, Singapore, 138634, Republic of Singapore
| | - Qianyu Lin
- Institute of Materials Research and Engineering (IMRE), Agency for Science, Technology and Research (A*STAR) #08-03, 2 Fusionopolis Way, Singapore, Singapore, 138634, Republic of Singapore
| | - Xinxin Zhao
- Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), 61 Biopolis Dr, Proteos, Singapore, Singapore, 138673, Republic of Singapore
| | - Xinyi Su
- Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), 61 Biopolis Dr, Proteos, Singapore, Singapore, 138673, Republic of Singapore
- Yong Loo Lin School of Medicine, National University of Singapore, 10 Medical Dr, Singapore, 117597
| | - Xian Jun Loh
- Institute of Materials Research and Engineering (IMRE), Agency for Science, Technology and Research (A*STAR) #08-03, 2 Fusionopolis Way, Singapore, Singapore, 138634, Republic of Singapore
- Department of Materials Science and Engineering, National University of Singapore (NUS), 9 Engineering Drive 1, Singapore, Singapore, 117576
| | - Jason Y C Lim
- Institute of Materials Research and Engineering (IMRE), Agency for Science, Technology and Research (A*STAR) #08-03, 2 Fusionopolis Way, Singapore, Singapore, 138634, Republic of Singapore
- Department of Materials Science and Engineering, National University of Singapore (NUS), 9 Engineering Drive 1, Singapore, Singapore, 117576
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5
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Kaufman CD, Farré C, Biscari L, Pérez AR, Alloatti A. Trypanosoma cruzi, Chagas disease and cancer: putting together the pieces of a complex puzzle. Front Cell Dev Biol 2023; 11:1260423. [PMID: 38188016 PMCID: PMC10768204 DOI: 10.3389/fcell.2023.1260423] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2023] [Accepted: 11/27/2023] [Indexed: 01/09/2024] Open
Abstract
Considering the extensive and widespread impact on individuals, cancer can presently be categorized as a pandemic. In many instances, the development of tumors has been linked to endemic microbe infections. Among parasitic infections, Trypanosoma cruzi stands out as one of the most extensively discussed protozoans in the literature that explores the association between diseases of parasite origin and cancer. However, the effective association remains an unsolved paradox. Both the parasite, along with protozoan-derived molecules, and the associated antiparasitic immune response can induce alterations in various host cell pathways, leading to modifications in cell cycle, metabolism, glycosylation, DNA mutations, or changes in neuronal signaling. Furthermore, the presence of the parasite can trigger cell death or a senescent phenotype and modulate the immune system, the metastatic cascade, and the formation of new blood vessels. The interaction among the parasite (and its molecules), the host, and cancer undoubtedly encompasses various mechanisms that operate differentially depending on the context. Remarkably, contrary to expectations, the evidence tilts the balance toward inhibiting tumor growth or resisting tumor development. This effect is primarily observed in malignant cells, rather than normal cells, indicating a selective or specific component. Nevertheless, nonspecific bystander mechanisms, such as T. cruzi's adjuvancy or the presence of proinflammatory cytokines, may also play a significant role in this phenomenon. This work aims to elucidate this complex scenario by synthesizing the main findings presented in the literature and by proposing new questions and answers, thereby adding pieces to this challenging puzzle.
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Affiliation(s)
- Cintia Daniela Kaufman
- Instituto de Inmunología Clínica y Experimental de Rosario (IDICER), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Universidad Nacional de Rosario, Rosario, Argentina
| | - Cecilia Farré
- Instituto de Inmunología Clínica y Experimental de Rosario (IDICER), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Universidad Nacional de Rosario, Rosario, Argentina
- Centro de Investigación y Producción de Reactivos Biológicos, Facultad de Ciencias Médicas, Universidad Nacional de Rosario, Rosario, Argentina
| | - Lucía Biscari
- Instituto de Inmunología Clínica y Experimental de Rosario (IDICER), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Universidad Nacional de Rosario, Rosario, Argentina
| | - Ana Rosa Pérez
- Instituto de Inmunología Clínica y Experimental de Rosario (IDICER), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Universidad Nacional de Rosario, Rosario, Argentina
| | - Andrés Alloatti
- Instituto de Inmunología Clínica y Experimental de Rosario (IDICER), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Universidad Nacional de Rosario, Rosario, Argentina
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6
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Wang J, Zheng Q, Wang H, Shi L, Wang G, Zhao Y, Fan C, Si J. Sesquiterpenes and Sesquiterpene Derivatives from Ferula: Their Chemical Structures, Biosynthetic Pathways, and Biological Properties. Antioxidants (Basel) 2023; 13:7. [PMID: 38275627 PMCID: PMC10812793 DOI: 10.3390/antiox13010007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2023] [Revised: 12/13/2023] [Accepted: 12/15/2023] [Indexed: 01/27/2024] Open
Abstract
Ferula is a genus of flowering plants known for its edible and medicinal properties. Since ancient times, many species of Ferula have been used in traditional medicine to treat various health issues across countries, such as digestive disorders, respiratory problems, and even as a remedy for headaches and toothaches. In addition, they are also used as a flavoring agent in various cuisines. As the main active ingredients in Ferula, sesquiterpenes and their derivatives, especially sesquiterpene coumarins, sesquiterpene phenylpropanoids, and sesquiterpene chromones, have attracted the attention of scientists due to the diversity of their chemical structures, as well as their extensive and promising biological properties, such as antioxidative, anti-inflammatory, antibacterial properties. However, there has not been a comprehensive review of sesquiterpenes and their derivatives from this plant. This review aims to provide an overview of the chemical structures, biosynthetic pathways, and biological properties of sesquiterpenes and sesquiterpene derivatives from Ferula, which may help guide future research directions and possible application methods for this valuable edible and medicinal plant.
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Affiliation(s)
- Junchi Wang
- The Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China; (J.W.); (Q.Z.); (H.W.)
| | - Qi Zheng
- The Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China; (J.W.); (Q.Z.); (H.W.)
| | - Huaxiang Wang
- The Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China; (J.W.); (Q.Z.); (H.W.)
| | - Leiling Shi
- Xinjiang Institute of Chinese Materia Medica and Ethnodrug, Urumqi 830002, China; (L.S.); (G.W.); (Y.Z.)
| | - Guoping Wang
- Xinjiang Institute of Chinese Materia Medica and Ethnodrug, Urumqi 830002, China; (L.S.); (G.W.); (Y.Z.)
| | - Yaqin Zhao
- Xinjiang Institute of Chinese Materia Medica and Ethnodrug, Urumqi 830002, China; (L.S.); (G.W.); (Y.Z.)
| | - Congzhao Fan
- Xinjiang Institute of Chinese Materia Medica and Ethnodrug, Urumqi 830002, China; (L.S.); (G.W.); (Y.Z.)
| | - Jianyong Si
- The Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China; (J.W.); (Q.Z.); (H.W.)
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Xie Y, Luo Z, Peng W, Liu Y, Yuan F, Xu J, Sun Y, Lu H, Wu T, Jiang L, Hu J. Inhibition of UTX/KDM6A improves recovery of spinal cord injury by attenuating BSCB permeability and macrophage infiltration through the MLCK/p-MLC pathway. J Neuroinflammation 2023; 20:259. [PMID: 37951955 PMCID: PMC10638785 DOI: 10.1186/s12974-023-02936-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2023] [Accepted: 10/18/2023] [Indexed: 11/14/2023] Open
Abstract
Spinal cord injury (SCI) can prompt an immediate disruption to the blood-spinal cord barrier (BSCB). Restoring the integrity of this barrier is vital for the recovery of neurological function post-SCI. The UTX protein, a histone demethylase, has been shown in previous research to promote vascular regeneration and neurological recovery in mice with SCI. However, it is unclear whether UTX knockout could facilitate the recovery of the BSCB by reducing its permeability. In this study, we systematically studied BSCB disruption and permeability at different time points after SCI and found that conditional UTX deletion in endothelial cells (ECs) can reduce BSCB permeability, decrease inflammatory cell infiltration and ROS production, and improve neurological function recovery after SCI. Subsequently, we used RNA sequencing and ChIP-qPCR to confirm that conditional UTX knockout in ECs can down-regulate expression of myosin light chain kinase (MLCK), which specifically mediates myosin light chain (MLC) phosphorylation and is involved in actin contraction, cell retraction, and tight junctions (TJs) protein integrity. Moreover, we found that MLCK overexpression can increase the ratio of p-MLC/MLC, further break TJs, and exacerbate BSCB deterioration. Overall, our findings indicate that UTX knockout could inhibit the MLCK/p-MLC pathway, resulting in decreased BSCB permeability, and ultimately promoting neurological recovery in mice. These results suggest that UTX is a promising new target for treating SCI.
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Affiliation(s)
- Yong Xie
- Department of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Changsha, China
- Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, China
- Hunan Engineering Research Center of Sports and Health, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Zixiang Luo
- Department of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Changsha, China
- Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, China
- Hunan Engineering Research Center of Sports and Health, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Wei Peng
- Department of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Changsha, China
- Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, China
- Hunan Engineering Research Center of Sports and Health, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Yudong Liu
- Department of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Changsha, China
- Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, China
- Hunan Engineering Research Center of Sports and Health, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Feifei Yuan
- Department of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Changsha, China
- Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, China
- Hunan Engineering Research Center of Sports and Health, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Jiaqi Xu
- Department of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Changsha, China
- Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, China
- Hunan Engineering Research Center of Sports and Health, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Yi Sun
- Department of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Changsha, China
- Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, China
- Hunan Engineering Research Center of Sports and Health, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Hongbin Lu
- Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, China
- Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, China
- Hunan Engineering Research Center of Sports and Health, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Tianding Wu
- Department of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Changsha, China.
- Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, China.
- Hunan Engineering Research Center of Sports and Health, Changsha, China.
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
| | - Liyuan Jiang
- Department of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Changsha, China.
- Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, China.
- Hunan Engineering Research Center of Sports and Health, Changsha, China.
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
| | - Jianzhong Hu
- Department of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Changsha, China.
- Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, China.
- Hunan Engineering Research Center of Sports and Health, Changsha, China.
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
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8
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Marongiu F, Cheri S, Laconi E. Clones of aging: When better fitness can be dangerous. Eur J Cell Biol 2023; 102:151340. [PMID: 37423036 DOI: 10.1016/j.ejcb.2023.151340] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Revised: 05/29/2023] [Accepted: 07/05/2023] [Indexed: 07/11/2023] Open
Abstract
The biological and clinical significance of aberrant clonal expansions in aged tissues is being intensely discussed. Evidence is accruing that these clones often result from the normal dynamics of cell turnover in our tissues. The aged tissue microenvironment is prone to favour the emergence of specific clones with higher fitness partly because of an overall decline in cell intrinsic regenerative potential of surrounding counterparts. Thus, expanding clones in aged tissues need not to be mechanistically associated with the development of cancer, albeit this is a possibility. We suggest that growth pattern is a critical phenotypic attribute that impacts on the fate of such clonal proliferations. The acquisition of a better proliferative fitness, coupled with a defect in tissue pattern formation, could represent a dangerous mix setting the stage for their evolution towards neoplasia.
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Affiliation(s)
- Fabio Marongiu
- Department of Biomedical Sciences, University of Cagliari, Italy
| | - Samuele Cheri
- Department of Biomedical Sciences, University of Cagliari, Italy
| | - Ezio Laconi
- Department of Biomedical Sciences, University of Cagliari, Italy.
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Raji E, Vahedian V, Golshanrad P, Nahavandi R, Behshood P, Soltani N, Gharibi M, Rashidi M, Maroufi NF. The potential therapeutic effects of Galbanic acid on cancer. Pathol Res Pract 2023; 248:154686. [PMID: 37487315 DOI: 10.1016/j.prp.2023.154686] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2023] [Revised: 07/10/2023] [Accepted: 07/11/2023] [Indexed: 07/26/2023]
Abstract
Galbanic acid (GBA), as a natural compound has potential anticancer properties. It has been documented that GBA shows promising therapeutic potential against various types of cancer, including breast, lung, colon, liver, and prostate cancer. Several mechanisms involve im anti-tumor effects of GBA include apoptosis induction, cell cycle arrest, inhibition of angiogenesis, suppression of metastasis, and modulation of immune responses. Furthermore, the synergistic effects of GBA along with chemotherapeutic agents led to has enhancing efficiency with reduction in toxicity. Moreover, GBA through antioxidant and anti-inflammatory properties possess indirect anti-tumor effects. In this review, we will summarize the anti-tumor effects of GBA acid along with involve mechanisms.
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Affiliation(s)
- Elahe Raji
- Department of Biology, Shahrekord Branch, Islamic Azad University, Iran
| | - Vahid Vahedian
- Department of Hematology, Transfusion Medicine and Cellular Therapy, Division of Hematology/oncology, Clinical Hospital, Faculty of Medicine, University of Sao Paulo (FMUSP-HC), Sao Paulo, Brazil; Department of Clinical Medicine, Laboratory of Medical Investigation in Pathogenesis and Targeted Therapy in Onco-Immuno-Hematology (LIM/31), Faculty of Medicine, University of Sao Paulo (FMUSP), Sao Paulo, Brazil
| | - Pezhman Golshanrad
- Sharif University of Technology (International Campus) Department of Computer Eng, Iran
| | - Reza Nahavandi
- Department of Biochemical and Pharmaceutical Engineering, School of Chemical Engineering, College of Engineering, University of Tehran, Tehran 11155-4563, Iran
| | - Parisa Behshood
- Department of Microbiology, Young Researchers and Elite Club, Shahrekord Branch, Islamic Azad University, Iran
| | - Nahal Soltani
- Department of Medical Laboratory Sciences, Faculty of Medicine, Islamic Azad University (IAU), Marand, Iran
| | - Mahdi Gharibi
- Department of pharmacy, Faculty of Pharmacy, University of Ankara, Ankara, Turkey
| | - Mohsen Rashidi
- The Department of Pharmacology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran; The Health of Plant and Livestock Products Research Center, Mazandaran University of Medical Sciences, Sari, Iran.
| | - Nazila Fathi Maroufi
- Department of Human Genetics, McGill University, Montreal, Canada; Victor Philip Dahdaleh Institute of Genomic Medicine at McGill University, Montreal, Canada; Department of Biochemistry and Clinical Laboratories, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
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10
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Basu A, Namporn T, Ruenraroengsak P. Critical Review in Designing Plant-Based Anticancer Nanoparticles against Hepatocellular Carcinoma. Pharmaceutics 2023; 15:1611. [PMID: 37376061 DOI: 10.3390/pharmaceutics15061611] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2023] [Revised: 05/19/2023] [Accepted: 05/22/2023] [Indexed: 06/29/2023] Open
Abstract
Hepatocellular carcinoma (HCC), accounting for 85% of liver cancer cases, continues to be the third leading cause of cancer-related deaths worldwide. Although various forms of chemotherapy and immunotherapy have been investigated in clinics, patients continue to suffer from high toxicity and undesirable side effects. Medicinal plants contain novel critical bioactives that can target multimodal oncogenic pathways; however, their clinical translation is often challenged due to poor aqueous solubility, low cellular uptake, and poor bioavailability. Nanoparticle-based drug delivery presents great opportunities in HCC therapy by increasing selectivity and transferring sufficient doses of bioactives to tumor areas with minimal damage to adjacent healthy cells. In fact, many phytochemicals encapsulated in FDA-approved nanocarriers have demonstrated the ability to modulate the tumor microenvironment. In this review, information about the mechanisms of promising plant bioactives against HCC is discussed and compared. Their benefits and risks as future nanotherapeutics are underscored. Nanocarriers that have been employed to encapsulate both pure bioactives and crude extracts for application in various HCC models are examined and compared. Finally, the current limitations in nanocarrier design, challenges related to the HCC microenvironment, and future opportunities are also discussed for the clinical translation of plant-based nanomedicines from bench to bedside.
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Affiliation(s)
- Aalok Basu
- Department of Pharmacy, Faculty of Pharmacy, Mahidol University, 447 Sri-Ayutthaya Rd., Rajathevi, Bangkok 10400, Thailand
| | - Thanaphon Namporn
- Department of Pharmacy, Faculty of Pharmacy, Mahidol University, 447 Sri-Ayutthaya Rd., Rajathevi, Bangkok 10400, Thailand
| | - Pakatip Ruenraroengsak
- Department of Pharmacy, Faculty of Pharmacy, Mahidol University, 447 Sri-Ayutthaya Rd., Rajathevi, Bangkok 10400, Thailand
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11
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Zhang Y, Dong P, Yang L. The role of nanotherapy in head and neck squamous cell carcinoma by targeting tumor microenvironment. Front Immunol 2023; 14:1189323. [PMID: 37292204 PMCID: PMC10244756 DOI: 10.3389/fimmu.2023.1189323] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2023] [Accepted: 05/15/2023] [Indexed: 06/10/2023] Open
Abstract
Head and neck squamous cell carcinomas (HNSCCs) refers to a group of highly malignant and pathogenically complex tumors. Traditional treatment methods include surgery, radiotherapy, and chemotherapy. However, with advancements in genetics, molecular medicine, and nanotherapy, more effective and safer treatments have been developed. Nanotherapy, in particular, has the potential to be an alternative therapeutic option for HNSCC patients, given its advantageous targeting capabilities, low toxicity and modifiability. Recent research has highlighted the important role of the tumor microenvironment (TME) in the development of HNSCC. The TME is composed of various cellular components, such as fibroblasts, vascular endothelial cells, and immune cells, as well as non-cellular agents such as cytokines, chemokines, growth factors, extracellular matrix (ECM), and extracellular vesicles (EVs). These components greatly influence the prognosis and therapeutic efficacy of HNSCC, making the TME a potential target for treatment using nanotherapy. By regulating angiogenesis, immune response, tumor metastasis and other factors, nanotherapy can potentially alleviate HNSCC symptoms. This review aims to summarize and discuss the application of nanotherapy that targets HNSCC's TME. We highlight the therapeutic value of nanotherapy for HNSCC patients.
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Affiliation(s)
- Ye Zhang
- Department of Radiation Oncology, Cancer Hospital of Dalian University of Technology/Liaoning Cancer Hospital and Institute, Shenyang, China
| | - Pengbo Dong
- School of Energy and Power Engineering, Dalian University of Technology, Dalian, China
| | - Lu Yang
- Department of Internal Medicine, Cancer Hospital of Dalian University of Technology/Liaoning Cancer Hospital and Institute, Shenyang, China
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12
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Khoury W, Trus R, Chen X, Baghaie L, Clark M, Szewczuk MR, El-Diasty M. Parsimonious Effect of Pentoxifylline on Angiogenesis: A Novel Pentoxifylline-Biased Adenosine G Protein-Coupled Receptor Signaling Platform. Cells 2023; 12:cells12081199. [PMID: 37190108 DOI: 10.3390/cells12081199] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2023] [Revised: 04/13/2023] [Accepted: 04/18/2023] [Indexed: 05/17/2023] Open
Abstract
Angiogenesis is the physiological process of developing new blood vessels to facilitate the delivery of oxygen and nutrients to meet the functional demands of growing tissues. It also plays a vital role in the development of neoplastic disorders. Pentoxifylline (PTX) is a vasoactive synthetic methyl xanthine derivative used for decades to manage chronic occlusive vascular disorders. Recently, it has been proposed that PTX might have an inhibitory effect on the angiogenesis process. Here, we reviewed the modulatory effects of PTX on angiogenesis and its potential benefits in the clinical setting. Twenty-two studies met the inclusion and exclusion criteria. While sixteen studies demonstrated that pentoxifylline had an antiangiogenic effect, four suggested it had a proangiogenic effect, and two other studies showed it did not affect angiogenesis. All studies were either in vivo animal studies or in vitro animal and human cell models. Our findings suggest that pentoxifylline may affect the angiogenic process in experimental models. However, there is insufficient evidence to establish its role as an anti-angiogenesis agent in the clinical setting. These gaps in our knowledge regarding how pentoxifylline is implicated in host-biased metabolically taxing angiogenic switch may be via its adenosine A2BAR G protein-coupled receptor (GPCR) mechanism. GPCR receptors reinforce the importance of research to understand the mechanistic action of these drugs on the body as promising metabolic candidates. The specific mechanisms and details of the effects of pentoxifylline on host metabolism and energy homeostasis remain to be elucidated.
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Affiliation(s)
- William Khoury
- School of Medicine, Queen's University, Kingston, ON K7L 3L4, Canada
| | - Ryan Trus
- Faculty of Arts and Science, Queen's University, Kingston, ON K7L 3N9, Canada
- School of Medicine, The Larner College of Medicine, University of Vermont, Burlington, VT 05405, USA
| | - Xingyu Chen
- School of Medicine, Queen's University, Kingston, ON K7L 3L4, Canada
| | - Leili Baghaie
- Department of Biomedical & Molecular Sciences, Queen's University, Kingston, ON K7L 3N6, Canada
| | - Mira Clark
- Faculty of Arts and Science, Queen's University, Kingston, ON K7L 3N9, Canada
- Department of Biomedical & Molecular Sciences, Queen's University, Kingston, ON K7L 3N6, Canada
| | - Myron R Szewczuk
- Department of Biomedical & Molecular Sciences, Queen's University, Kingston, ON K7L 3N6, Canada
| | - Mohammad El-Diasty
- Division of Cardiac Surgery, Queen's University, Kingston, ON K7L 2V7, Canada
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13
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Moeinabadi‐Bidgoli K, Rezaee M, Hossein‐Khannazer N, Babajani A, Aghdaei HA, Arki MK, Afaghi S, Niknejad H, Vosough M. Exosomes for angiogenesis induction in ischemic disorders. J Cell Mol Med 2023; 27:763-787. [PMID: 36786037 PMCID: PMC10003030 DOI: 10.1111/jcmm.17689] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2022] [Revised: 01/19/2023] [Accepted: 01/26/2023] [Indexed: 02/15/2023] Open
Abstract
Ischaemic disorders are leading causes of morbidity and mortality worldwide. While the current therapeutic approaches have improved life expectancy and quality of life, they are unable to "cure" ischemic diseases and instate regeneration of damaged tissues. Exosomes are a class of extracellular vesicles with an average size of 100-150 nm, secreted by many cell types and considered a potent factor of cells for paracrine effects. Since exosomes contain multiple bioactive components such as growth factors, molecular intermediates of different intracellular pathways, microRNAs and nucleic acids, they are considered as cell-free therapeutics. Besides, exosomes do not rise cell therapy concerns such as teratoma formation, alloreactivity and thrombotic events. In addition, exosomes are stored and utilized more convenient. Interestingly, exosomes could be an ideal complementary therapeutic tool for ischemic disorders. In this review, we discussed therapeutic functions of exosomes in ischemic disorders including angiogenesis induction through various mechanisms with specific attention to vascular endothelial growth factor pathway. Furthermore, different delivery routes of exosomes and different modification strategies including cell preconditioning, gene modification and bioconjugation, were highlighted. Finally, pre-clinical and clinical investigations in which exosomes were used were discussed.
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Affiliation(s)
- Kasra Moeinabadi‐Bidgoli
- Basic and Molecular Epidemiology of Gastroenterology Disorders Research CenterShahid Beheshti University of Medical SciencesTehranIran
| | - Malihe Rezaee
- School of MedicineShahid Beheshti University of Medical SciencesTehranIran
| | - Nikoo Hossein‐Khannazer
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver DiseasesShahid Beheshti University of Medical SciencesTehranIran
| | - Amirhesam Babajani
- Oncopathology Research CenterIran University of Medical SciencesTehranIran
| | - Hamid Asadzadeh Aghdaei
- Basic and Molecular Epidemiology of Gastroenterology Disorders Research CenterShahid Beheshti University of Medical SciencesTehranIran
| | - Mandana Kazem Arki
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver DiseasesShahid Beheshti University of Medical SciencesTehranIran
| | - Siamak Afaghi
- Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine SciencesShahid Beheshti University of Medical SciencesTehranIran
| | - Hassan Niknejad
- Oncopathology Research CenterIran University of Medical SciencesTehranIran
| | - Massoud Vosough
- Department of Regenerative Medicine, Cell Science Research CenterRoyan Institute for Stem Cell Biology and Technology, ACECRTehranIran
- Experimental Cancer Medicine, Institution for Laboratory MedicineKarolinska InstituteStockholmSweden
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14
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Pang C, Nisbet R, Gibson M, Evans N, Khalifa M, Papadopoulou A, Tsui J, Hamilton G, Brookes J, Lim CS. Early follow-up quality of life and mental health of patients with congenital vascular malformations cared for in a multi-disciplinary specialist centre. Phlebology 2023; 38:80-90. [PMID: 36541140 DOI: 10.1177/02683555221147469] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
OBJECTIVE The study aimed to evaluate the early follow-up quality of life (QoL), pain and mental health of patients with congenital vascular malformation (CVM) from a variety of treatment options. METHODS All patients with CVM who received care and had follow-up between February 1st 2018 and January 31st 2020 were included. The health-related QoL, pain, and mental health were assessed with RAND Health Care 36-Item Short Form Survey (SF-36), visual analogue score for pain (VAS-P) and Hospital Anxiety and Depression Scale (HADS). Paired t-test was used for all analyses. p < .05 were considered significant. RESULTS In total, 110 patients with a mean age of 36.9 years were included in this study. In all patients following care, significant improvement was found in the bodily pain domain of SF-36 and VAS-P (both p = .01). This was largely driven by high-flow vascular malformation patients who responded better to embolo-sclerotherapy, which revealed significant improvement in the bodily pain domain of SF-36 (p = .002) and VAS-P (p = .02). Patients who received supportive treatment only reported significant improvement in mental health (p = .004) and social functioning (p = .03) domains of SF-36. Meanwhile, patients treated with embolo-sclerotherapy reported significant improvement only in VAS-P (p = .02). CONCLUSIONS This study concluded that the effects of care on early follow-up QoL, pain and mental health of patients with CVM were heterogenous. Future research should therefore, include larger sample size and longer term follow-up to understand the various factors that affect the QoL and mental health of these patients, as well as the holistic approaches to manage them.
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Affiliation(s)
- Calver Pang
- Department of Vascular Surgery, 4965Royal Free London NHS Foundation Trust, London, UK.,Department of Surgical Biotechnology, Division of Surgery & Interventional Science, Faculty of Medical Sciences, University College London, London, UK
| | - Rebecca Nisbet
- Department of Vascular Surgery, 4965Royal Free London NHS Foundation Trust, London, UK
| | - Michael Gibson
- Department of Vascular Surgery, 4965Royal Free London NHS Foundation Trust, London, UK
| | - Nicholas Evans
- Department of Vascular Surgery, 4965Royal Free London NHS Foundation Trust, London, UK
| | - Mohamed Khalifa
- Department of Interventional Radiology, 4965Royal Free London NHS Foundation Trust, London, UK
| | - Anthie Papadopoulou
- Department of Interventional Radiology, 4965Royal Free London NHS Foundation Trust, London, UK
| | - Janice Tsui
- Department of Vascular Surgery, 4965Royal Free London NHS Foundation Trust, London, UK.,Department of Surgical Biotechnology, Division of Surgery & Interventional Science, Faculty of Medical Sciences, University College London, London, UK
| | - George Hamilton
- Department of Vascular Surgery, 4965Royal Free London NHS Foundation Trust, London, UK.,Department of Surgical Biotechnology, Division of Surgery & Interventional Science, Faculty of Medical Sciences, University College London, London, UK
| | - Jocelyn Brookes
- Department of Vascular Surgery, 4965Royal Free London NHS Foundation Trust, London, UK.,Department of Interventional Radiology, 4965Royal Free London NHS Foundation Trust, London, UK
| | - Chung Sim Lim
- Department of Vascular Surgery, 4965Royal Free London NHS Foundation Trust, London, UK.,Department of Surgical Biotechnology, Division of Surgery & Interventional Science, Faculty of Medical Sciences, University College London, London, UK
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15
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Kim M, Lee KW, Kim K, Gulenko O, Lee C, Keum B, Chun HJ, Choi HS, Kim CU, Yang JM. Intra-instrument channel workable, optical-resolution photoacoustic and ultrasonic mini-probe system for gastrointestinal endoscopy. PHOTOACOUSTICS 2022; 26:100346. [PMID: 35313458 PMCID: PMC8933520 DOI: 10.1016/j.pacs.2022.100346] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/23/2022] [Accepted: 03/08/2022] [Indexed: 05/04/2023]
Abstract
There has been a long-standing expectation that the optical-resolution embodiment of photoacoustic tomography could have a substantial impact on gastrointestinal endoscopy by enabling microscopic visualization of the vasculature based on the endogenous contrast mechanism. Although multiple studies have demonstrated the in vivo imaging capability of a developed imaging device over the last decade, the implementation of such an endoscopic system that can be applied immediately when necessary via the instrument channel of a video endoscope has been a challenge. In this study, we developed a 3.38-mm diameter catheter-based, integrated optical-resolution photoacoustic and ultrasonic mini-probe system and successfully demonstrated its intra-instrument channel workability for the standard 3.7-mm diameter instrument channel of a clinical video endoscope based on a swine model. Through the instrument channel, we acquired the first in vivo dual-mode photoacoustic and ultrasonic endoscopic images from the esophagogastric junction of a swine. Further, in a rat colorectum in vivo imaging experiment, we visualized hierarchically developed mesh-like capillary networks with a hole size as small as ~50 µm, which suggests the potential level of image details that could be photoacoustically provided in clinical settings in the future.
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Affiliation(s)
- Minjae Kim
- Center for Photoacoustic Medical Instruments, Department of Biomedical Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, South Korea
| | - Kang Won Lee
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University College of Medicine, Seoul 02841, South Korea
| | - KiSik Kim
- Center for Photoacoustic Medical Instruments, Department of Biomedical Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, South Korea
| | - Oleksandra Gulenko
- Center for Photoacoustic Medical Instruments, Department of Biomedical Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, South Korea
| | - Cheol Lee
- Department of Physics, UNIST, Ulsan 44919, South Korea
| | - Bora Keum
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University College of Medicine, Seoul 02841, South Korea
| | - Hoon Jai Chun
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University College of Medicine, Seoul 02841, South Korea
| | - Hyuk Soon Choi
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University College of Medicine, Seoul 02841, South Korea
| | - Chae Un Kim
- Department of Physics, UNIST, Ulsan 44919, South Korea
| | - Joon-Mo Yang
- Center for Photoacoustic Medical Instruments, Department of Biomedical Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, South Korea
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16
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Diverse roles of tumor-stromal PDGFB-to-PDGFRβ signaling in breast cancer growth and metastasis. Adv Cancer Res 2022; 154:93-140. [PMID: 35459473 DOI: 10.1016/bs.acr.2022.01.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Over the last couple of decades, it has become increasingly apparent that the tumor microenvironment (TME) mediates every step of cancer progression and solid tumors are only able to metastasize with a permissive TME. This intricate interaction of cancer cells with their surrounding TME, or stroma, is becoming more understood with an ever greater knowledge of tumor-stromal signaling pairs such as platelet-derived growth factors (PDGF) and their cognate receptors. We and others have focused our research efforts on understanding how tumor-derived PDGFB activates platelet-derived growth factor receptor beta (PDGFRβ) signaling specifically in the breast cancer TME. In this chapter, we broadly discuss PDGF and PDGFR expression patterns and signaling in normal physiology and breast cancer. We then detail the expansive roles played by the PDGFB-to-PDGFRβ signaling pathway in modulating breast tumor growth and metastasis with a focus on specific cellular populations within the TME, which are responsive to tumor-derived PDGFB. Given the increasingly appreciated importance of PDGFB-to-PDGFRβ signaling in breast cancer progression, specifically in promoting metastasis, we end by discussing how therapeutic targeting of PDGFB-to-PDGFRβ signaling holds great promise for improving current breast cancer treatment strategies.
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17
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Floriano JF, Emanueli C, Vega S, Barbosa AMP, Oliveira RGD, Floriano EAF, Graeff CFDO, Abbade JF, Herculano RD, Sobrevia L, Rudge MVC. Pro-angiogenic approach for skeletal muscle regeneration. Biochim Biophys Acta Gen Subj 2022; 1866:130059. [PMID: 34793875 DOI: 10.1016/j.bbagen.2021.130059] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2021] [Accepted: 11/01/2021] [Indexed: 12/19/2022]
Abstract
The angiogenesis process is a phenomenon in which numerous molecules participate in the stimulation of the new vessels' formation from pre-existing vessels. Angiogenesis is a crucial step in tissue regeneration and recovery of organ and tissue function. Muscle diseases affect millions of people worldwide overcome the ability of skeletal muscle to self-repair. Pro-angiogenic therapies are key in skeletal muscle regeneration where both myogenesis and angiogenesis occur. These therapies have been based on mesenchymal stem cells (MSCs), exosomes, microRNAs (miRs) and delivery of biological factors. The use of different calls of biomaterials is another approach, including ceramics, composites, and polymers. Natural polymers are use due its bioactivity and biocompatibility in addition to its use as scaffolds and in drug delivery systems. One of these polymers is the natural rubber latex (NRL) which is biocompatible, bioactive, versatile, low-costing, and capable of promoting tissue regeneration and angiogenesis. In this review, the advances in the field of pro-angiogenic therapies are discussed.
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Affiliation(s)
- Juliana Ferreira Floriano
- São Paulo State University (UNESP), Botucatu Medical School, Botucatu, São Paulo 18.618-687, Brazil; National Heart and Lung Institute, Imperial College London, London, UK.
| | - Costanza Emanueli
- National Heart and Lung Institute, Imperial College London, London, UK
| | - Sofia Vega
- São Paulo State University (UNESP), Botucatu Medical School, Botucatu, São Paulo 18.618-687, Brazil; Cellular and Molecular Physiology Laboratory (CMPL), Department of Obstetrics, Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago 8330024, Chile
| | | | | | | | | | - Joelcio Francisco Abbade
- São Paulo State University (UNESP), Botucatu Medical School, Botucatu, São Paulo 18.618-687, Brazil
| | | | - Luis Sobrevia
- São Paulo State University (UNESP), Botucatu Medical School, Botucatu, São Paulo 18.618-687, Brazil; Cellular and Molecular Physiology Laboratory (CMPL), Department of Obstetrics, Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago 8330024, Chile; Department of Physiology, Faculty of Pharmacy, Universidad de Sevilla, Seville E-41012, Spain; University of Queensland, Centre for Clinical Research (UQCCR), Faculty of Medicine and Biomedical Sciences, University of Queensland, Herston, QLD, 4029, Queensland, Australia; Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, 9713GZ Groningen, the Netherlands.
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18
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Karami E, Naderi S, Roshan R, Behdani M, Kazemi-Lomedasht F. Targeted therapy of angiogenesis using anti-VEGFR2 and anti-NRP-1 nanobodies. Cancer Chemother Pharmacol 2022; 89:165-172. [PMID: 34988654 DOI: 10.1007/s00280-021-04372-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2021] [Accepted: 11/03/2021] [Indexed: 12/24/2022]
Abstract
PURPOSE Targeted therapy in cancer researches is a promising approach that can resolve drawbacks of systematic therapeutics. Nanobodies are potent therapeutics due to their high specificity and affinity to the target. METHODS In this study, we evaluated the effect of the combination of anti-vascular endothelial growth factor receptor 2 (anti-VEGFR2) and anti-neuropilin-1 (anti-NRP1) nanobodies both in vitro (MTT, and tube formation assay) and in vivo (chick chorioallantoic membrane (CAM), and Nude mice treatment assay). RESULTS Our results showed that the combination of two nanobodies (anti-VEGFR2/NRP-1 nanobodies) significantly inhibited proliferation as well as tube formation of human endothelial cells effective than a single nanobody. In addition, the mixture of both nanobodies inhibited vascularization of chick chorioallantoic membrane ex ovo CAM assay as compared to a single nanobody. Moreover, the mixture of both nanobodies significantly inhibited tumor growth of the mice (tumor volume and weight) higher than individual nanobodies (P < 0.05). CONCLUSION Our results offer a promising role of combination therapies in cancer therapy as well as angiogenesis.
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Affiliation(s)
- Elmira Karami
- Venom and Biotherapeutics Molecules Laboratory, Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran
| | - Shamsi Naderi
- Venom and Biotherapeutics Molecules Laboratory, Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran
| | - Reyhaneh Roshan
- Venom and Biotherapeutics Molecules Laboratory, Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran
| | - Mahdi Behdani
- Venom and Biotherapeutics Molecules Laboratory, Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran
| | - Fatemeh Kazemi-Lomedasht
- Venom and Biotherapeutics Molecules Laboratory, Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.
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19
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Yurtdaş-Kırımlıoğlu G, Görgülü Ş, Güleç K, Kıyan HT. Nanoarchitectonics of PLGA based polymeric nanoparticles with oseltamivir phosphate for lung cancer therapy: In vitro-in vivo evaluation. J Drug Deliv Sci Technol 2022. [DOI: 10.1016/j.jddst.2021.102996] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
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20
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Tu J, Li W, Yang S, Yang P, Yan Q, Wang S, Lai K, Bai X, Wu C, Ding W, Cooper‐White J, Diwan A, Yang C, Yang H, Zou J. Single-Cell Transcriptome Profiling Reveals Multicellular Ecosystem of Nucleus Pulposus during Degeneration Progression. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2022; 9:e2103631. [PMID: 34825784 PMCID: PMC8787427 DOI: 10.1002/advs.202103631] [Citation(s) in RCA: 57] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/20/2021] [Revised: 10/22/2021] [Indexed: 05/13/2023]
Abstract
Although degeneration of the nucleus pulposus (NP) is a major contributor to intervertebral disc degeneration (IVDD) and low back pain, the underlying molecular complexity and cellular heterogeneity remain poorly understood. Here, a comprehensive single-cell resolution transcript landscape of human NP is reported. Six novel human NP cells (NPCs) populations are identified by their distinct molecular signatures. The potential functional differences among NPC subpopulations are analyzed. Predictive transcripts, transcriptional factors, and signal pathways with respect to degeneration grades are explored. It is reported that fibroNPCs is the subpopulation for end-stage degeneration. CD90+NPCs are observed to be progenitor cells in degenerative NP tissues. NP-infiltrating immune cells comprise a previously unrecognized diversity of cell types, including granulocytic myeloid-derived suppressor cells (G-MDSCs). Integrin αM (CD11b) and oxidized low density lipoprotein receptor 1 (OLR1) as surface markers of NP-derived G-MDSCs are uncovered. The G-MDSCs are found to be enriched in mildly degenerated (grade II and III) NP tissues compared to severely degenerated (grade IV and V) NP tissues. Their immunosuppressive function and alleviation effects on NPCs' matrix degradation are revealed in vitro. Collectively, this study reveals the NPC-type complexity and phenotypic characteristics in NP, thereby providing new insights and clues for IVDD treatment.
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Affiliation(s)
- Ji Tu
- Department of Orthopaedic SurgeryThe First Affiliated Hospital of Soochow UniversitySuzhou215006China
- Spine Labs, St. George and Sutherland Clinical SchoolFaculty of MedicineUniversity of New South WalesSydneyNew South Wales2217Australia
| | - Wentian Li
- Spine Labs, St. George and Sutherland Clinical SchoolFaculty of MedicineUniversity of New South WalesSydneyNew South Wales2217Australia
| | - Sidong Yang
- Australian Institute for Bioengineering and NanotechnologyThe University of QueenslandSt. LuciaBrisbaneQueensland4072Australia
- Department of Spine SurgeryThe Third Hospital of Hebei Medical UniversityShijiazhuang05000China
| | - Pengyi Yang
- Charles Perkins CentreThe University of SydneySydneyNSW2006Australia
- School of Life and Environmental SciencesThe University of SydneySydneyNSW2006Australia
- Computational Systems Biology GroupChildren's Medical Research InstituteFaculty of Medicine and HealthThe University of SydneyWestmeadNSW2145Australia
| | - Qi Yan
- Department of Orthopaedic SurgeryThe First Affiliated Hospital of Soochow UniversitySuzhou215006China
| | - Shenyu Wang
- Department of Orthopaedic SurgeryThe First Affiliated Hospital of Soochow UniversitySuzhou215006China
| | - Kaitao Lai
- The ANZAC Research InstituteConcord Repatriation General HospitalSydneyNSW2139Australia
- Concord Clinical SchoolFaculty of Medicine and HealthThe University of SydneySydneyNSW2139Australia
| | - Xupeng Bai
- Cancer Care CentreSt. George and Sutherland Clinical SchoolFaculty of MedicineUniversity of New South WalesSydneyNew South Wales2052Australia
| | - Cenhao Wu
- Department of Orthopaedic SurgeryThe First Affiliated Hospital of Soochow UniversitySuzhou215006China
| | - Wenyuan Ding
- Department of Spine SurgeryThe Third Hospital of Hebei Medical UniversityShijiazhuang05000China
| | - Justin Cooper‐White
- Australian Institute for Bioengineering and NanotechnologyThe University of QueenslandSt. LuciaBrisbaneQueensland4072Australia
- School of Chemical EngineeringThe University of QueenslandBrisbaneQueensland4072Australia
| | - Ashish Diwan
- Spine Labs, St. George and Sutherland Clinical SchoolFaculty of MedicineUniversity of New South WalesSydneyNew South Wales2217Australia
- Spine ServiceDepartment of Orthopaedic SurgerySt. George HospitalKogarahNew South Wales2217Australia
| | - Cao Yang
- Department of Orthopaedic SurgeryWuhan Union HospitalTongji Medical SchoolHuazhong University of Science and TechnologyWuhanHubei430022China
| | - Huilin Yang
- Department of Orthopaedic SurgeryThe First Affiliated Hospital of Soochow UniversitySuzhou215006China
| | - Jun Zou
- Department of Orthopaedic SurgeryThe First Affiliated Hospital of Soochow UniversitySuzhou215006China
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21
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Qin F, Lin S, Deng K, Qin J, Xu Z, Yuan L, Wei J, Sun Y, Zheng T, Li S. Comprehensive analysis of angiogenesis subtype of squamous cell carcinoma. World J Surg Oncol 2021; 19:275. [PMID: 34521431 PMCID: PMC8442455 DOI: 10.1186/s12957-021-02367-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2021] [Accepted: 08/10/2021] [Indexed: 12/26/2022] Open
Abstract
Background Squamous cell carcinoma (SCC) is a disease with distinct management complexities as it displays a remarkably heterogeneous molecular subtype. However, the landscape of angiogenesis for SCC is not fully investigated. Method and materials The angiogenesis-related subtypes of SCC were established by using the ConsensusClusterPlus package based on angiogenesis-related genes and TCGA data. We analyzed the alteration of genes and miRNAs as well as pathways associated with angiogenesis subtypes. Next, the regulation network, the correlation with genomic characteristics, immune microenvironment, and clinical features of the angiogenesis subtypes were further investigated. Finally, the prognostic impact of the angiogenesis-related subtypes for SCC was also analyzed. Results A total of 1368 SCC samples were included in this study. Two angiogenesis subtypes were then identified based on the one hundred and sixty-three angiogenesis-related genes with subtype1 (angiogenesis subtype) of 951 SCC patients and subtype2 (non-angiogenesis subtype) of 417 SCC. GSEA revealed that angiogenesis and epithelial-mesenchymal transition, inflammatory response, and hypoxia were enriched in the angiogenesis subtype. Eight of the 15 immune checkpoints (ADORA2A, BTLA, CD276, CYBB, HAVCR2, SIGLEC7, SIGLEC9, and VTCN1) were significantly upregulated while C10orf54 were significantly downregulated in the angiogenesis subtype. The survival analysis revealed that the patients in the angiogenesis subtype have poorer survival outcomes than those in the non-angiogenesis subtype (P = 0.017 for disease-free interval and P = 0.00013 for overall survival). Conclusion Our analysis revealed a novel angiogenesis subtype classification in SCC and provides new insights into a hallmark of SCC progression.
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Affiliation(s)
- Fanglu Qin
- Department of Thoracic and Cardiovascular Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Zhuang Autonomous Region, People's Republic of China.,Guangxi Medical University, Nanning, 530021, Guangxi Zhuang Autonomous Region, People's Republic of China
| | - Shenghua Lin
- Department of Thoracic and Cardiovascular Surgery, People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530021, Guangxi Zhuang Autonomous Region, People's Republic of China
| | - Kun Deng
- Department of Thoracic and Cardiovascular Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Zhuang Autonomous Region, People's Republic of China
| | - Junqi Qin
- Department of Thoracic and Cardiovascular Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Zhuang Autonomous Region, People's Republic of China
| | - Zhanyu Xu
- Department of Thoracic and Cardiovascular Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Zhuang Autonomous Region, People's Republic of China
| | - Liqiang Yuan
- Department of Thoracic and Cardiovascular Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Zhuang Autonomous Region, People's Republic of China
| | - Jiangbo Wei
- Department of Thoracic and Cardiovascular Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Zhuang Autonomous Region, People's Republic of China
| | - Yu Sun
- Department of Thoracic and Cardiovascular Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Zhuang Autonomous Region, People's Republic of China
| | - Tiaozhan Zheng
- Department of Thoracic and Cardiovascular Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Zhuang Autonomous Region, People's Republic of China
| | - Shikang Li
- Department of Thoracic and Cardiovascular Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Zhuang Autonomous Region, People's Republic of China.
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22
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Oseltamivir phosphate loaded pegylated-Eudragit nanoparticles for lung cancer therapy: Characterization, prolonged release, cytotoxicity profile, apoptosis pathways and in vivo anti-angiogenic effect by using CAM assay. Microvasc Res 2021; 139:104251. [PMID: 34520775 DOI: 10.1016/j.mvr.2021.104251] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2021] [Revised: 08/12/2021] [Accepted: 09/06/2021] [Indexed: 12/13/2022]
Abstract
The target of the current investigation was the delivery of oseltamivir phosphate (OSE) into the lung adenocarcinoma tissues by means of designing nanosized, non-toxic and biocompatible pegylated Eudragit based NPs and investigating their anticancer and antiangiogenic activity. The rationale for this strategy is to provide a novel perspective to cancer treatment with OSE loaded pegylated ERS NPs under favor of smaller particle size, biocompatible feature, cationic characteristic, examining their selective effectiveness on lung cell lines (A549 lung cancer cell line and CCD-19Lu normal cell line) and examining antiangiogenic activity by in vivo CAM analysis. For this purpose, OSE encapsulated pegylated ERS based NPs were developed and investigated for zeta potential, particle size, encapsulation efficiency, morphology, DSC, FT-IR, 1H NMR analyses. In vitro release, cytotoxicity, determination apoptotic pathways and in vivo CAM assay were carried out. Considering characterizations, NPs showed smaller particle size, cationic zeta potential, relatively higher EE%, nearly spherical shape, amorphous matrix formation and prolonged release pattern (Peppas-Sahlin and Weibull model with Fickian and non-Fickian release mechanisms). Flow cytometry was used to assess the apoptotic pathways using the Annexin V-FITC/PI staining assay, FITC Active Caspase-3 staining assay, and mitochondrial membrane potential detection tests. Activations on caspase-3 pathways made us think that OSE loaded pegylated ERS NPs triggered to apoptosis using intrinsic pathway. As regards to the in vivo studies, OSE loaded pegylated ERS based NPs demonstrated strong and moderate antiangiogenic activity for ERS-OSE 2 and ERS-OSE 3, respectively. With its cationic character, smaller particle size, relative superior EE%, homogenous amorphous polymeric matrix constitution indicated using solid state tests, prolonged release manner, highly selective to the human lung adenocarcinoma cell lines, could trigger apoptosis intrinsically and effectively, possess good in vivo antiangiogenic activity, ERS-OSE 2 formulation is chosen as a promising candidate and a potent drug delivery system to treat lung cancer.
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23
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Han N, Pan Z, Liu G, Yang R, Yujing B. Hypoxia: The "Invisible Pusher" of Gut Microbiota. Front Microbiol 2021; 12:690600. [PMID: 34367091 PMCID: PMC8339470 DOI: 10.3389/fmicb.2021.690600] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2021] [Accepted: 06/25/2021] [Indexed: 12/20/2022] Open
Abstract
Oxygen is important to the human body. Cell survival and operations depend on oxygen. When the body becomes hypoxic, it affects the organs, tissues and cells and can cause irreversible damage. Hypoxia can occur under various conditions, including external environmental hypoxia and internal hypoxia. The gut microbiota plays different roles under hypoxic conditions, and its products and metabolites interact with susceptible tissues. This review was conducted to elucidate the complex relationship between hypoxia and the gut microbiota under different conditions. We describe the changes of intestinal microbiota under different hypoxic conditions: external environment and internal environment. For external environment, altitude was the mayor cause induced hypoxia. With the increase of altitude, hypoxia will become more serious, and meanwhile gut microbiota also changed obviously. Body internal environment also became hypoxia because of some diseases (such as cancer, neonatal necrotizing enterocolitis, even COVID-19). In addition to the disease itself, this hypoxia can also lead to changes of gut microbiota. The relationship between hypoxia and the gut microbiota are discussed under these conditions.
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Affiliation(s)
- Ni Han
- State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China
| | - Zhiyuan Pan
- State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China
| | - Guangwei Liu
- Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, Institute of Cell Biology, College of Life Sciences, Beijing Normal University, Beijing, China
| | - Ruifu Yang
- State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China
| | - Bi Yujing
- State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China
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24
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Lai E, Cascinu S, Scartozzi M. Are All Anti-Angiogenic Drugs the Same in the Treatment of Second-Line Metastatic Colorectal Cancer? Expert Opinion on Clinical Practice. Front Oncol 2021; 11:637823. [PMID: 34041019 PMCID: PMC8141840 DOI: 10.3389/fonc.2021.637823] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2020] [Accepted: 04/19/2021] [Indexed: 12/28/2022] Open
Abstract
Targeting tumor-driven angiogenesis is an effective strategy in the management of metastatic colorectal cancer (mCRC); however, the choice of second-line therapy is complicated by the availability of several drugs, the occurrence of resistance and the lack of validated prognostic and predictive biomarkers. This review examines the use of angiogenesis-targeted therapies for the second-line management of mCRC patients. Mechanisms of resistance and anti-placental growth factor agents are discussed, and the role of aflibercept, a recombinant fusion protein consisting of portions of human vascular endothelial growth factor receptor (VEGFR)-1 and VEGFR-2, is highlighted. The novel mechanism of action of aflibercept makes it a useful second-line agent in mCRC patients progressing after oxaliplatin-based chemotherapy, as well as in those with resistance after bevacizumab.
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Affiliation(s)
- Eleonora Lai
- Medical Oncology Unit, University Hospital and University of Cagliari, Cagliari, Italy
| | - Stefano Cascinu
- Oncologia Medica, Università Vita-Salute, IRCCS Ospedale San Raffaele, Milano, Italy
| | - Mario Scartozzi
- Medical Oncology Unit, University Hospital and University of Cagliari, Cagliari, Italy
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25
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Tamamouna V, Rahman MM, Petersson M, Charalambous I, Kux K, Mainor H, Bolender V, Isbilir B, Edgar BA, Pitsouli C. Remodelling of oxygen-transporting tracheoles drives intestinal regeneration and tumorigenesis in Drosophila. Nat Cell Biol 2021; 23:497-510. [PMID: 33972730 PMCID: PMC8567841 DOI: 10.1038/s41556-021-00674-1] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2020] [Accepted: 03/31/2021] [Indexed: 02/03/2023]
Abstract
The Drosophila trachea, as the functional equivalent of mammalian blood vessels, senses hypoxia and oxygenates the body. Here, we show that the adult intestinal tracheae are dynamic and respond to enteric infection, oxidative agents and tumours with increased terminal branching. Increased tracheation is necessary for efficient damage-induced intestinal stem cell (ISC)-mediated regeneration and is sufficient to drive ISC proliferation in undamaged intestines. Gut damage or tumours induce HIF-1α (Sima in Drosophila), which stimulates tracheole branching via the FGF (Branchless (Bnl))-FGFR (Breathless (Btl)) signalling cascade. Bnl-Btl signalling is required in the intestinal epithelium and the trachea for efficient damage-induced tracheal remodelling and ISC proliferation. Chemical or Pseudomonas-generated reactive oxygen species directly affect the trachea and are necessary for branching and intestinal regeneration. Similarly, tracheole branching and the resulting increase in oxygenation are essential for intestinal tumour growth. We have identified a mechanism of tracheal-intestinal tissue communication, whereby damage and tumours induce neo-tracheogenesis in Drosophila, a process reminiscent of cancer-induced neoangiogenesis in mammals.
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Affiliation(s)
- Vasilia Tamamouna
- University of Cyprus, Department of Biological Sciences, 1 Panepistimiou Avenue, 2109 Aglantzia, Cyprus
| | - M. Mahidur Rahman
- Huntsman Cancer Institute, Department of Oncological Sciences, University of Utah, Salt Lake City, UT 84112, USA
| | - Monika Petersson
- German Cancer Research Center (DKFZ)-Center for Molecular Biology (ZMBH), University of Heidelberg Alliance, Im Neuenheimer Feld 282, 69120 Heidelberg, Germany
| | - Irini Charalambous
- University of Cyprus, Department of Biological Sciences, 1 Panepistimiou Avenue, 2109 Aglantzia, Cyprus
| | - Kristina Kux
- University of Cyprus, Department of Biological Sciences, 1 Panepistimiou Avenue, 2109 Aglantzia, Cyprus
| | - Hannah Mainor
- Huntsman Cancer Institute, Department of Oncological Sciences, University of Utah, Salt Lake City, UT 84112, USA
| | - Verena Bolender
- German Cancer Research Center (DKFZ)-Center for Molecular Biology (ZMBH), University of Heidelberg Alliance, Im Neuenheimer Feld 282, 69120 Heidelberg, Germany
| | - Buse Isbilir
- German Cancer Research Center (DKFZ)-Center for Molecular Biology (ZMBH), University of Heidelberg Alliance, Im Neuenheimer Feld 282, 69120 Heidelberg, Germany
| | - Bruce A. Edgar
- Huntsman Cancer Institute, Department of Oncological Sciences, University of Utah, Salt Lake City, UT 84112, USA,Corresponding authors ,
| | - Chrysoula Pitsouli
- University of Cyprus, Department of Biological Sciences, 1 Panepistimiou Avenue, 2109 Aglantzia, Cyprus,Corresponding authors ,
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26
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Ghazaryan N, Movsisyan N, Macedo JC, Vaz S, Ayvazyan N, Pardo L, Logarinho E. Macrovipera lebetina obtusa Snake Venom as a Modulator of Antitumor Effect in S-180 Sarcoma Mouse Model. Mol Biol 2021. [DOI: 10.1134/s0026893321020217] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
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27
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Bansal Y, Minhas R, Singhal A, Arora RK, Bansal G. Benzimidazole: A Multifacted Nucelus for Anticancer Agents. CURR ORG CHEM 2021. [DOI: 10.2174/1385272825666210208141107] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Cancer is characterized by an uncontrolled proliferation of cells, dedifferentiation,
invasiveness and metastasis. Endothelial growth factor (eGF), insulin-like growth factor
(IGF), platelet-derived growth factor (PDGF), Fibroblast growth factor (FGF), Vascular endothelial
growth factor (VEGF), checkpoint kinase 1 & 2 ( Chk1 & Chk2), aurora kinases,
topoisomerases, histone deacetylators (HDAC), poly(ADP-Ribose)polymerase (PARP), farnesyl
transferases, RAS-MAPK pathway and PI3K-Akt-mTOR pathway, are some of the
prominent mediators implicated in the proliferation of tumor cells. Huge artillery of natural
and synthetic compounds as anticancer, which act by inhibiting one or more of the enzymes
and/or pathways responsible for the progression of tumor cells, is reported in the literature.
The major limitations of anticancer agents used in clinics as well as of those under development
in literature are normal cell toxicity and other side effects due to lack of specificity.
Hence, medicinal chemists across the globe have been working for decades to develop potent and safe anticancer
agents from natural sources as well as from different classes of heterocycles. Benzimidazole is one of the most important
and explored heteronucelus because of their versatility in biological actions as well as synthetic applications
in medicinal chemistry. The structural similarity of amino derivatives of benzimidazole with purines makes it a fascinating
nucleus for the development of anticancer, antimicrobial and anti-HIV agents. This review article is an attempt
to critically analyze various reports on benzimidazole derivatives acting on different targets to act as anticancer so as
to understand the structural requirements around benzimidazole nucleus for each target and enable medicinal chemists
to promote rational development of antitumor agents.
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Affiliation(s)
- Yogita Bansal
- Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala - 147002, India
| | - Richa Minhas
- Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala - 147002, India
| | - Ankit Singhal
- Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala - 147002, India
| | - Radhey Krishan Arora
- Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala - 147002, India
| | - Gulshan Bansal
- Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala - 147002, India
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28
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Zheng X, Gao H, Zhang Y, Cui X, Jia R, Xue J, Tang W, Wang Y, Li H, Chen X, Wang H. Development of a rapid and sensitive UPLC-MS/MS assay for simultaneous quantitation of Vorolanib and its metabolite in human plasma and application to a pharmacokinetics study. J Pharm Biomed Anal 2021; 199:114034. [PMID: 33774456 DOI: 10.1016/j.jpba.2021.114034] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2021] [Revised: 03/18/2021] [Accepted: 03/19/2021] [Indexed: 11/17/2022]
Abstract
Vorolanib is an oral tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR). A sensitive and specific LC-MS/MS assay was developed and fully validated for simultaneous quantification of vorolanib and its main metabolite X297 in human plasma. The two analytes were extracted from K2-EDTA plasma samples by protein precipitation (PP) with acetonitrile, and chromatographically separated on a C18 reverse-phase column using a gradient elution. A SCIEX 5500 QTRAP® mass spectrometer system was operated in multiple-reaction monitoring mode (MRM) and all components were detected using positive electrospray ionization (ESI). The results successfully demonstrated that the method had satisfactory linearity, sensitivity, and selectivity in the concentration ranges of vorolanib (1.00-1000 ng/mL) and X297 (0.500-500 ng/mL). In this study, two concentration related peaks in the vorolanib and X297 detection channels were observed, which were speculated to be isomers of vorolanib and X297. In order to standardize the sample pretreatment process, the effect of lamp light and pH on the isomer reconversion was evaluated. The results indicated, that the exposure of samples to lamp light during the handling procedures, did not cause the conversion of the isomers. For the first time a robust and specific ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) assay for the high-throughput quantification of vorolanib and X297 in human plasma was established and validated following bioanalytical validation guidelines. The proposed method was successfully applied to clinical trials evaluating the pharmacokinetics of vorolanib tablets in Chinese advanced solid tumor patients.
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Affiliation(s)
- Xin Zheng
- Clinical Pharmacology Research Center, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China
| | - Huitao Gao
- Clinical Pharmacology Research Center, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China
| | - Yanbao Zhang
- Clinical Pharmacology Research Center, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China
| | - Xinge Cui
- Clinical Pharmacology Research Center, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China
| | - Ranran Jia
- Clinical Pharmacology Research Center, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China
| | - Junli Xue
- Shanghai East Hospital, Tongji University, Shanghai 200123, China
| | - Wenbo Tang
- Shanghai East Hospital, Tongji University, Shanghai 200123, China
| | - Yang Wang
- Betta Pharmaceuticals Co., Ltd, China
| | - Hua Li
- Betta Pharmaceuticals Co., Ltd, China
| | | | - Hongyun Wang
- Clinical Pharmacology Research Center, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China.
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29
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Han C, Zhang Z, Sun J, Li K, Li Y, Ren C, Meng Q, Yang J. Self-Assembling Peptide-Based Hydrogels in Angiogenesis. Int J Nanomedicine 2020; 15:10257-10269. [PMID: 33364757 PMCID: PMC7751603 DOI: 10.2147/ijn.s277046] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2020] [Accepted: 10/22/2020] [Indexed: 12/22/2022] Open
Abstract
Ischemic diseases, especially in the heart and the brain, have become a serious threat to human health. Growth factor and cell therapy are emerging as promising therapeutic strategies; however, their retention and sustainable functions in the injured tissue are limited. Self-assembling peptide (SAP)-based hydrogels, mimicking the extracellular matrix, are therefore introduced to encapsulate and controllably release cells, cell-derived exosomes or growth factors, thus promoting angiogenesis and tissue recovery after ischemia. We will summarize the classification, composition and structure of SAPs, and the influencing factors for SAP gelation. Moreover, we will describe the functionalized SAPs, and the combinatorial therapy of cells, exosomes or growth factors with functionalized SAPs for angiogenic process as well as its advantage in immunogenicity and injectability. Finally, an outlook on future directions and challenges is provided.
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Affiliation(s)
- Chaoshan Han
- Department of Biomedical Engineering, School of Medicine and School of Engineering, University of Alabama at Birmingham, Birmingham, AL 35294, USA
| | - Zhiwei Zhang
- Department of Cardiothoracic Surgery, The Second Affiliated Hospital of Soochow University, Suzhou 215006, People's Republic of China
| | - Jiacheng Sun
- Department of Biomedical Engineering, School of Medicine and School of Engineering, University of Alabama at Birmingham, Birmingham, AL 35294, USA
| | - Ke Li
- Department of Burn and Plastic Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, People's Republic of China
| | - Yangxin Li
- Department of Cardiovascular Surgery of the First Affiliated Hospital & Institute for Cardiovascular Science, Soochow University, Suzhou 215006, People's Republic of China
| | - Chuanlu Ren
- Department of Clinical Laboratory, The 904th Hospital of the People's Liberation Army, Wuxi 214044, People's Republic of China
| | - Qingyou Meng
- Department of Cardiovascular Surgery of the First Affiliated Hospital & Institute for Cardiovascular Science, Soochow University, Suzhou 215006, People's Republic of China
| | - Junjie Yang
- Department of Biomedical Engineering, School of Medicine and School of Engineering, University of Alabama at Birmingham, Birmingham, AL 35294, USA
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30
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Duru G, van Egmond M, Heemskerk N. A Window of Opportunity: Targeting Cancer Endothelium to Enhance Immunotherapy. Front Immunol 2020; 11:584723. [PMID: 33262763 PMCID: PMC7686513 DOI: 10.3389/fimmu.2020.584723] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2020] [Accepted: 10/19/2020] [Indexed: 12/19/2022] Open
Abstract
Vascular abnormalities in tumors have a major impact on the immune microenvironment in tumors. The consequences of abnormal vasculature include increased hypoxia, acidosis, high intra-tumoral fluid pressure, and angiogenesis. This introduces an immunosuppressive microenvironment that alters immune cell maturation, activation, and trafficking, which supports tumor immune evasion and dissemination of tumor cells. Increasing data suggests that cancer endothelium is a major barrier for traveling leukocytes, ranging from a partial blockade resulting in a selective endothelial barrier, to a complete immune infiltration blockade associated with immune exclusion and immune desert cancer phenotypes. Failed immune cell trafficking as well as immunosuppression within the tumor microenvironment limits the efficacy of immunotherapeutic approaches. As such, targeting proteins with key roles in angiogenesis may potentially reduce immunosuppression and might restore infiltration of anti-tumor immune cells, creating a therapeutic window for successful immunotherapy. In this review, we provide a comprehensive overview of established as well as more controversial endothelial pathways that govern selective immune cell trafficking across cancer endothelium. Additionally, we discuss recent insights and strategies that target tumor vasculature in order to increase infiltration of cytotoxic immune cells during the therapeutic window of vascular normalization hereby improving the efficacy of immunotherapy.
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Affiliation(s)
- Gizem Duru
- Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Molecular Cell Biology and Immunology, Cancer Center Amsterdam, Amsterdam Infection & Immunity, Amsterdam, Netherlands
| | - Marjolein van Egmond
- Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Molecular Cell Biology and Immunology, Cancer Center Amsterdam, Amsterdam Infection & Immunity, Amsterdam, Netherlands
- Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Surgery, Cancer Center Amsterdam, Amsterdam, Netherlands
| | - Niels Heemskerk
- Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Molecular Cell Biology and Immunology, Cancer Center Amsterdam, Amsterdam Infection & Immunity, Amsterdam, Netherlands
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31
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Shimoda M, Ohtsuka T, Okada Y, Kanai Y. Stromal metalloproteinases: Crucial contributors to the tumor microenvironment. Pathol Int 2020; 71:1-14. [PMID: 33074556 DOI: 10.1111/pin.13033] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2020] [Accepted: 09/25/2020] [Indexed: 12/30/2022]
Abstract
Proteolytic balance is crucial for the maintenance of tissue homeostasis. In cancer, dysregulated proteolysis is involved in unregulated tissue remodeling and inflammation, leading to the promotion of tumor growth, local invasion, and metastasis. Metalloproteinases, which were first identified as collagen cleaving enzymes, have been shown to extensively degrade extracellular matrix proteins or selectively release cell surface-bound cytokines, growth factors, or their receptors, thereby impacting extracellular matrix integrity, immune cell recruitment and tissue turnover. Although tumor cells produce various metalloproteinases, the major source is thought to be stromal cells infiltrating the tumor. Different types of stromal cells express specific sets of metalloproteinases and their inhibitors, which specifically alter the milieu within the tumor. In this review, recent findings and knowledge regarding metalloproteinases derived from stromal cells during the creation of the tumor microenvironment are described and their contribution to the tumor progression and metastasis discussed.
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Affiliation(s)
- Masayuki Shimoda
- Department of Pathology, Keio University School of Medicine, Tokyo, Japan
| | - Takashi Ohtsuka
- Division of Thoracic Surgery, Department of Surgery, The Jikei University School of Medicine, Tokyo, Japan
| | - Yasunori Okada
- Department of Pathophysiology for Locomotive and Neoplastic Diseases, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Yae Kanai
- Department of Pathology, Keio University School of Medicine, Tokyo, Japan
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32
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He Y, Zhang Y, Qin HY, Gu DY, Lu X, Hu JX, Ye WL, He GB. Inhibitory effect of 5-FU loaded ultrasound microbubbles on tumor growth and angiogenesis. Bioorg Med Chem Lett 2020; 30:127534. [PMID: 32898694 DOI: 10.1016/j.bmcl.2020.127534] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2020] [Revised: 08/26/2020] [Accepted: 08/31/2020] [Indexed: 12/20/2022]
Abstract
The anti-neovascularization treatment is one of the effective strategies for tumor molecular target therapy. At present, the target and effect of the anti-neovascularization treatment is limited, and it is urgent to establish a new vascular targeting strategy to effectively treat tumors. In this work, we used high intensity focused ultrasound (HIFU) combined with targeted microbubbles to establish a molecular targeted ultrasound response microbubble for neovascular cells. Furthermore, the effects of drug loaded microbubbles on neovascularization and tumor cells were studied. The tumor vascular targeted and ultrasound-responsive microbubbles of 5-FU@DLL4-MBs were prepared by the thin-film dispersion method. The size and zeta potential of 5-FU@DLL4-MBs was about 1248 nm and -9.1 mV. 5-FU@DLL4-MBs released 5-FU showed an ultrasound-responsive manner, and had better vascular-targeting ability. Furthermore, the 5-FU@DLL4-MBs showed the strongest cytotoxic effect on HUVECs or HepG-2 cells and can be effectively internalized into the HUVECs cells. Thus, 5-FU@DLL4-MBs combined with HIFU can be considered as a potential method for antitumor angiogenesis in the future.
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Affiliation(s)
- Yang He
- Department of Ultrasound Diagnosis, Xijing Hospital, Fourth Military Medical University, Xi'an 710038, China
| | - Yue Zhang
- Department of Ultrasound Diagnosis, Xijing Hospital, Fourth Military Medical University, Xi'an 710038, China
| | - Hai-Ying Qin
- Department of Ultrasound Diagnosis, Xijing Hospital, Fourth Military Medical University, Xi'an 710038, China
| | - Dong-Yue Gu
- Department of Ultrasound Diagnosis, Xijing Hospital, Fourth Military Medical University, Xi'an 710038, China
| | - Xiao Lu
- Department of Ultrasound Diagnosis, Xijing Hospital, Fourth Military Medical University, Xi'an 710038, China
| | - Jin-Xi Hu
- Department of Ultrasound Diagnosis, Xijing Hospital, Fourth Military Medical University, Xi'an 710038, China
| | - Wei-Liang Ye
- Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China.
| | - Guang-Bin He
- Department of Ultrasound Diagnosis, Xijing Hospital, Fourth Military Medical University, Xi'an 710038, China.
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Qian W, Huang P, Liang X, Chen Y, Guan B. High expression of carcinoembryonic antigen-associated cell adhesion molecule 1 is associated with microangiogenesis in esophageal squamous cell carcinoma. Transl Cancer Res 2020; 9:4762-4769. [PMID: 35117839 PMCID: PMC8798924 DOI: 10.21037/tcr-19-2039] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2019] [Accepted: 07/14/2020] [Indexed: 01/05/2023]
Abstract
Background Carcinoembryonic antigen-associated cell adhesion molecule 1 (CEACAM1) plays an important role in tumor progression, invasion, and metastasis by regulating angiogenesis. However, the expression of CEACAM1 in esophageal cancer tissues and its relationship with microvessel density (MVD) has not been investigated before. Methods MVD and the expression of CEACAM1 in 80 esophageal squamous cell carcinoma (ESCC) tissues were determined by immunohistochemistry (IHC). Statistical analyses were conducted to test the associations between CEACAM1 expression, MVD level, clinicopathologic factors, and prognosis. Results The expression level of CEACAM1 was significantly correlated with the level of MVD. Kaplan-Meier analysis showed no significant correlations between local recurrence and distant metastasis in high MVD and high CEACAM-1 expression group. Kaplan-Meier analysis also showed a poorer survival rate in patients with high MVD or high CEACAM-1. Univariate analysis showed that MVD levels, CEACAM1 expression, lymph node metastasis, and patient's age were prognostic factors for postoperative ESCC. The results of multivariate analysis indicated that the significance of the prognostic effect of CEACAM-1 expression observed by univariate analysis disappeared when analyzed together with MVD, suggesting that the prognostic impact of CEACAM1 expression was dependent on MVD level, while MVD was still a significant prognostic factor for adverse cancer-related survival (P=0.001). Conclusions The CEACAM1 expression is a potential prognostic factor for postoperative ESCC combined with MVD level.
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Affiliation(s)
- Weihua Qian
- Department of Oncology, Zhangjiagang Hospital of Traditional Chinese Medicine affiliated to Nanjing University of Chinese Medicine, Suzhou, China
| | - Pan Huang
- Department of Oncology, Zhangjiagang Hospital of Traditional Chinese Medicine affiliated to Nanjing University of Chinese Medicine, Suzhou, China.,The First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, China
| | - Xiaohong Liang
- Department of Respiratory, Zhangjiagang Hospital of Traditional Chinese Medicine affiliated to Nanjing University of Chinese Medicine, Suzhou, China
| | - Yuan Chen
- Department of Central Research Laboratory, The Second Hospital of Shandong University, Jinan, China
| | - Bingxin Guan
- Department of Pathology, The Second Hospital of Shandong University, Jinan, China
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Rajora AK, Ravishankar D, Zhang H, Rosenholm JM. Recent Advances and Impact of Chemotherapeutic and Antiangiogenic Nanoformulations for Combination Cancer Therapy. Pharmaceutics 2020; 12:pharmaceutics12060592. [PMID: 32630584 PMCID: PMC7356724 DOI: 10.3390/pharmaceutics12060592] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2020] [Revised: 06/17/2020] [Accepted: 06/18/2020] [Indexed: 12/16/2022] Open
Abstract
Traditional chemotherapy, along with antiangiogenesis drugs (combination cancer therapy), has shown reduced tumor recurrence and improved antitumor effects, as tumor growth and metastasis are often dependent on tumor vascularization. However, the effect of combination chemotherapy, including synergism and additive and even antagonism effects, depends on drug combinations in an optimized ratio. Hence, nanoformulations are ideal, demonstrating a great potential for the combination therapy of chemo-antiangiogenesis for cancer. The rationale for designing various nanocarriers for combination therapy is derived from organic (polymer, lipid), inorganic, or hybrid materials. In particular, hybrid nanocarriers that consist of more than one material construct provide flexibility for different modes of entrapment within the same carrier—e.g., physical adsorption, encapsulation, and chemical conjugation strategies. These multifunctional nanocarriers can thus be used to co-deliver chemo- and antiangiogenesis drugs with tunable drug release at target sites. Hence, this review attempts to survey the most recent advances in nanoformulations and their impact on cancer treatment in a combined regimen—i.e., conventional cytotoxic and antiangiogenesis agents. The mechanisms and site-specific co-delivery strategies are also discussed herein, along with future prospects.
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Affiliation(s)
- Amit Kumar Rajora
- Pharmaceutical Sciences Laboratory, Faculty of Science and Engineering, Åbo Akademi University, 20520 Turku, Finland;
- Correspondence: (A.K.R.); (J.M.R.)
| | - Divyashree Ravishankar
- Bioscience Department, Sygnature Discovery, Bio City, Pennyfoot St, Nottingham NG1 1GR, UK;
| | - Hongbo Zhang
- Pharmaceutical Sciences Laboratory, Faculty of Science and Engineering, Åbo Akademi University, 20520 Turku, Finland;
- Turku Bioscience Center, University of Turku and Åbo Akademi University, 20520 Turku, Finland
| | - Jessica M. Rosenholm
- Pharmaceutical Sciences Laboratory, Faculty of Science and Engineering, Åbo Akademi University, 20520 Turku, Finland;
- Correspondence: (A.K.R.); (J.M.R.)
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Ju M, Cheng H, Qu K, Lu X. Efficacy and safety of ramucirumab treatment in patients with advanced colorectal cancer: A protocol for systematic review and meta analysis. Medicine (Baltimore) 2020; 99:e20618. [PMID: 32541497 PMCID: PMC7302601 DOI: 10.1097/md.0000000000020618] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2020] [Accepted: 05/08/2020] [Indexed: 01/22/2023] Open
Abstract
BACKGROUND vascular endothelial growth factor receptor 2 (VEGFR-2) has an important role in colorectal cancer pathogenesis and progression. The aim of our study is to provide a protocol for assessing the efficacy and safety of ramucirumab (a monoclonal antibody VEGFR-2 antagonist) for the treatment of advanced colorectal cancer. METHODS The systematic review will be reported according to the preferred reporting items for systematic reviews and meta-analyses protocols. Relevant randomized controlled trials were searched from PubMed, Cochrane Library, Web of Science, Excerpt Medica Database, China National Knowledge Infrastructure, and Wanfang Database. Papers in English or Chinese published from their inception to February 2020 will be included without any restrictions.Study selection and data extraction will be performed independently by 2 investigators. The clinical outcomes including overall response rate, complete response rate (disease control rate), overall survival, progression-free survival, quality of life, immune function, and adverse events, were systematically evaluated. Review Manager 5.3 and Stata 14.0 were used for data analysis, and a fixed or random-effect model of meta-analysis will be used depending upon the heterogeneity observed between studies. Subgroup analysis will be carried out depending on the availability of sufficient clinical data. RESULTS AND CONCLUSION The findings of this systematic review and meta-analysis will be published in a peer-reviewed journal, and provide more evidence-based guidance in clinical practice. PROSPERO REGISTRATION NUMBER CRD42020165683.
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Affiliation(s)
- Man Ju
- Department of Anus & Intestine Surgery
| | - Honggang Cheng
- Department of Gastrointestinal Surgery, Liaocheng People's Hospital, Liaocheng, Shandong Province
| | - Kai Qu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi Province
| | - Xiangqian Lu
- Department of Radiotherapy, Liaocheng People's Hospital, Liaocheng, Shandong Province, China
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Yildirim H, Aydemir O, Balbaba M, Özercan İH, İlhan N. Comparison of the effect of topical bevacizumab and sorafenib in experimental corneal neovascularization. Cutan Ocul Toxicol 2020; 39:223-228. [PMID: 32338080 DOI: 10.1080/15569527.2020.1760877] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
Abstract
PURPOSE The purpose of this study was to compare the neovascularization inhibiting the effect of topical bevacizumab and sorafenib and to determine the effective dose of sorafenib. MATERIAL AND METHODS Forty-two healthy Wistar albino rats were randomly divided into six groups. The right corneas of all rats except group 1 were cauterised with silver nitrate. Group 2 received DMSO, group 3 received topical bevacizumab (5 mg/dL, 3 times a day) and group 4, 5 and 6 received topical sorafenib (2.5 mg/dl, 5 mg/dL, 7.5 mg/dL, 2 times a day respectively), between days 1 and 7. Corneal photographs were taken on day 8 and the corneal neovascular area percentage was calculated. Following decapitation, the corneas were removed to determine the levels of VEGF ELİSA and corneal immune staining. The Mann-Whitney U-test was used for statistical analysis. RESULTS The neovascular corneal area percentage was statistically significantly lower in the treatment groups than group 2 (p < 0.05). The intensity of VEGF immune staining was also lower in groups 3, 5 and 6 from the group 2. Group 3, 5 and 6 were no significant differences compared to group 1. The VEGF ELİSA levels were statistically significantly lower in group 3, 5 and 6 compared to group 2 (p < 0.05). There was no statistically difference between VEGF ELİSA levels of group 2 and 4 (p > 0.05). CONCLUSIONS Sorafenib was as effective as bevacizumab in the regression of corneal neovascularization. The effect of sorafenib seems to be dose-dependent. The low doses and twice a day administration are important advantages of sorafenib.
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Affiliation(s)
- Hakan Yildirim
- Faculty of Medicine, Department of Ophthalmology, Firat University, Elazig, Turkey
| | - Orhan Aydemir
- Faculty of Medicine, Department of Ophthalmology, Firat University, Elazig, Turkey
| | - Mehmet Balbaba
- Faculty of Medicine, Department of Ophthalmology, Firat University, Elazig, Turkey
| | | | - Nevin İlhan
- Faculty of Medicine, Department of Biochemistry, Firat University, Elazig, Turkey
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Wang M, Ye Q, Mao D, Li H. Research Progress in Liver-Regenerating Microenvironment and DNA Methylation in Hepatocellular Carcinoma: The Role of Traditional Chinese Medicine. Med Sci Monit 2020; 26:e920310. [PMID: 32144233 PMCID: PMC7077739 DOI: 10.12659/msm.920310] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2019] [Accepted: 12/10/2019] [Indexed: 12/11/2022] Open
Abstract
The development, progression, recurrence, and metastasis of hepatocellular carcinoma (HCC) are closely associated with an abnormal liver-regenerating microenvironment (LRM). Therefore, preventing and reversing an abnormal LRM is a potential therapeutic strategy against HCC. Studies are increasingly focusing on the impact of regeneration, fibrosis, angiogenesis, inflammation, immunomodulation, and hepatic stem cells on HCC development and progression. As a key epigenetic mechanism, DNA methylation is extensively involved in regulating physiological and pathological pathways. In this review, we summarize recent findings on the role of DNA methylation in the fibrotic, angiogenic, inflammatory/immune, and stem cell microenvironments of HCC, and discuss new advances in Traditional Chinese Medicine (TCM) on influencing the abnormal LRM, so as to gain new insights into alleviating the abnormal LRM via regulating DNA methylation by TCM.
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Affiliation(s)
- Minggang Wang
- Hubei University of Traditional Chinese Medicine, Wuhan, Hubei, P.R. China
| | - Qianling Ye
- Guangxi University of Traditional Chinese Medicine, Nanning, Guangxi, P.R. China
| | - Dewen Mao
- The First Affiliated Hospital of Guangxi University of Traditional Chinese Medicine, Nanning, Guangxi, P.R. China
| | - Hanmin Li
- Hubei University of Traditional Chinese Medicine, Wuhan, Hubei, P.R. China
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Vartanian AA, Khochenkov DA, Khochenkova YA, Machkova YS, Khachatryan DS, Kolotaev AV, Balaev AN, Ohmanovich KA, Osipov VN. Effect of Derivatives of Hydroxamic Acids on Vasculogenic Mimicry. RUSSIAN JOURNAL OF BIOORGANIC CHEMISTRY 2020. [DOI: 10.1134/s106816202002017x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
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Wang H, Rao B, Lou J, Li J, Liu Z, Li A, Cui G, Ren Z, Yu Z. The Function of the HGF/c-Met Axis in Hepatocellular Carcinoma. Front Cell Dev Biol 2020; 8:55. [PMID: 32117981 PMCID: PMC7018668 DOI: 10.3389/fcell.2020.00055] [Citation(s) in RCA: 97] [Impact Index Per Article: 19.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2019] [Accepted: 01/22/2020] [Indexed: 12/17/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide, leading to a large global cancer burden. Hepatocyte growth factor (HGF) and its high-affinity receptor, mesenchymal epithelial transition factor (c-Met), are closely related to the onset, progression, and metastasis of multiple tumors. The HGF/c-Met axis is involved in cell proliferation, movement, differentiation, invasion, angiogenesis, and apoptosis by activating multiple downstream signaling pathways. In this review, we focus on the function of the HGF/c-Met axis in HCC. The HGF/c-Met axis promotes the onset, proliferation, invasion, and metastasis of HCC. Moreover, it can serve as a biomarker for diagnosis and prognosis, as well as a therapeutic target for HCC. In addition, it is closely related to drug resistance during HCC treatment.
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Affiliation(s)
- Haiyu Wang
- Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Gene Hospital of Henan Province, Precision Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Benchen Rao
- Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Gene Hospital of Henan Province, Precision Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Jiamin Lou
- Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Gene Hospital of Henan Province, Precision Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Jianhao Li
- Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Gene Hospital of Henan Province, Precision Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Zhenguo Liu
- Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Gene Hospital of Henan Province, Precision Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Ang Li
- Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Gene Hospital of Henan Province, Precision Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Guangying Cui
- Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Gene Hospital of Henan Province, Precision Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Zhigang Ren
- Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Gene Hospital of Henan Province, Precision Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Zujiang Yu
- Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Gene Hospital of Henan Province, Precision Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
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Structural bases that underline Trypanosoma cruzi calreticulin proinfective, antiangiogenic and antitumor properties. Immunobiology 2019; 225:151863. [PMID: 31732192 DOI: 10.1016/j.imbio.2019.10.012] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2019] [Accepted: 10/29/2019] [Indexed: 12/24/2022]
Abstract
Microbes have developed mechanisms to resist the host immune defenses and some elicit antitumor immune responses. About 6 million people are infected with Trypanosoma cruzi, the protozoan agent of Chagas' disease, the sixth neglected tropical disease worldwide. Eighty years ago, G. Roskin and N. Klyuyeva proposed that T. cruzi infection mediates an anti-cancer activity. This observation has been reproduced by several other laboratories, but no molecular basis has been proposed. We have shown that the highly pleiotropic chaperone calreticulin (TcCalr, formerly known as TcCRT), translocates from the parasite ER to the exterior, where it mediates infection. Similar to its human counterpart HuCALR (formerly known as HuCRT), TcCalr inhibits C1 in its capacity to initiate the classical pathway of complement activation. We have also proposed that TcCalr inhibits angiogenesis and it is a likely mediator of antitumor effects. We have generated several in silico structural TcCalr models to delimit a peptide (VC-TcCalr) at the TcCalr N-domain. Chemically synthesized VC-TcCalr did bind to C1q and was anti-angiogenic in Gallus gallus chorioallantoic membrane assays. These properties were associated with structural features, as determined in silico. VC-TcCalr, a strong dipole, interacts with charged proteins such as collagen-like tails and scavenger receptors. Comparatively, HuCALR has less polarity and spatial stability, probably due to at least substitutions of Gln for Gly, Arg for Lys, Arg for Asp and Ser for Arg that hinder protein-protein interactions. These differences can explain, at least in part, how TcCalr inhibits the complement activation pathway and has higher efficiency as an antiangiogenic and antitumor agent than HuCALR.
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Lu RM, Chiu CY, Liu IJ, Chang YL, Liu YJ, Wu HC. Novel human Ab against vascular endothelial growth factor receptor 2 shows therapeutic potential for leukemia and prostate cancer. Cancer Sci 2019; 110:3773-3787. [PMID: 31578782 PMCID: PMC6890446 DOI: 10.1111/cas.14208] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2019] [Revised: 09/25/2019] [Accepted: 09/25/2019] [Indexed: 12/15/2022] Open
Abstract
Vascular endothelial growth factor receptor 2 (VEGFR2) is highly expressed in tumor‐associated endothelial cells, where it modulates tumor‐promoting angiogenesis, and it is also found on the surface of tumor cells. Currently, there are no Ab therapeutics targeting VEGFR2 approved for the treatment of prostate cancer or leukemia. Therefore, development of novel efficacious anti‐VEGFR2 Abs will benefit cancer patients. We used the Institute of Cellular and Organismic Biology human Ab library and affinity maturation to develop a fully human Ab, anti‐VEGFR2‐AF, which shows excellent VEGFR2 binding activity. Anti‐VEGFR2‐AF bound Ig‐like domain 3 of VEGFR2 extracellular region to disrupt the interaction between VEGF‐A and VEGFR2, neutralizing downstream signaling of the receptor. Moreover, anti‐VEGFR2‐AF inhibited capillary structure formation and exerted Ab‐dependent cell‐mediated cytotoxicity and complement‐dependent cytotoxicity in vitro. We found that VEGFR2 is expressed in PC‐3 human prostate cancer cell line and associated with malignancy and metastasis of human prostate cancer. In a PC‐3 xenograft mouse model, treatment with anti‐VEGFR2‐AF repressed tumor growth and angiogenesis as effectively and safely as US FDA‐approved anti‐VEGFR2 therapeutic, ramucirumab. We also report for the first time that addition of anti‐VEGFR2 Ab can enhance the efficacy of docetaxel in the treatment of a prostate cancer mouse model. In HL‐60 human leukemia‐xenografted mice, anti‐VEGFR2‐AF showed better efficacy than ramucirumab with prolonged survival and reduced metastasis of leukemia cells to ovaries and lymph nodes. Our findings suggest that anti‐VEGFR2‐AF has strong potential as a cancer therapy that could directly target VEGFR2‐expressing tumor cells in addition to its anti‐angiogenic action.
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Affiliation(s)
- Ruei-Min Lu
- Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan
| | - Chiung-Yi Chiu
- Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan
| | - I-Ju Liu
- Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan
| | - Yu-Ling Chang
- Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan
| | - Yaw-Jen Liu
- Research and Development Center, United Biopharma Inc., Hsinshu, Taiwan
| | - Han-Chung Wu
- Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan
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Macarulla T, Montagut C, Sánchez-Martin FJ, Granja M, Verdaguer H, Sastre J, Tabernero J. The role of PIGF blockade in the treatment of colorectal cancer: overcoming the pitfalls. Expert Opin Biol Ther 2019; 20:15-22. [PMID: 31608707 DOI: 10.1080/14712598.2020.1677603] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Introduction: In colorectal cancer, anti-VEGF agents have demonstrated a survival benefit when combined with chemotherapy. However, development of resistance is very common. One of the mechanisms is due not to a failure in the VEGFR blockade, but rather to development of compensatory mechanisms of resistance, such as hypoxia-triggered upregulation of other proangiogenic factors, like placental growth factor (PlGF).Areas covered: This article summarizes the fundamental role of PlGF in the development of resistance to antiangiogenic treatment as well as the efficacy of aflibercept, ramucirumab, and regorafenib.Expert opinion: Aflibercept functions as a soluble decoy receptor precluding VEGFs and PlGF from binding to native VEGFR, and therefore preventing the emergence of resistance. Bevacizumab limits its function to preventing the interaction between VEGF-A and VEGFR. In combination with FOLFIRI (VELOUR trial), aflibercept improves survival in patients with metastatic CRC who are resistant or have progressed to oxaliplatin-based chemotherapy. Ramucirumab, a fully humanized immunoglobulin G1 (IgG-1) monoclonal antibody and regorafenib, a multikinase inhibitor, have significant improvement for overall survival as well as for progression-free survival in chemotherapy refractory settings.
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Affiliation(s)
- Teresa Macarulla
- Vall d´Hebron University Hospital (HUVH) and Vall d'Hebron Institute of Oncology (VHIO), Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Clara Montagut
- Hospital del Mar, Barcelona, Spain.,Institut Mar d'Investigacions Mèdiques (IMIM), Barcelona, Spain.,Universitat Pompeu Fabra, Barcelona, Spain
| | | | | | - Helena Verdaguer
- Vall d´Hebron University Hospital (HUVH) and Vall d'Hebron Institute of Oncology (VHIO), Universitat Autònoma de Barcelona, Barcelona, Spain
| | | | - Josep Tabernero
- Vall d´Hebron University Hospital (HUVH) and Vall d'Hebron Institute of Oncology (VHIO), Universitat Autònoma de Barcelona, Barcelona, Spain
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Borah S, Vasudevan D, Swain RK. C-type lectin family XIV members and angiogenesis. Oncol Lett 2019; 18:3954-3962. [PMID: 31579078 DOI: 10.3892/ol.2019.10760] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2019] [Accepted: 05/29/2019] [Indexed: 12/21/2022] Open
Abstract
The growth and metastasis of tumors is dependent on angiogenesis. C-type lectins are carbohydrate-binding proteins with a diverse range of functions. The C-type lectin family XIV members are transmembrane glycoproteins, and all four members of this family have been reported to regulate angiogenesis, although the detailed mechanism of action has yet to be completely elucidated. They interact with extracellular matrix proteins and mediate cell-cell adhesion by their lectin-like domain. The aim of the present study was to summarize the available information on the function and mechanism of C-type lectin family XIV in angiogenesis and discuss their potential as targets for cancer therapy.
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Affiliation(s)
- Supriya Borah
- Institute of Life Sciences, Bhubaneswar, Odisha 751023, India.,Department of Biotechnology, Manipal Academy of Higher Education, Manipal, Karnataka 576104, India
| | | | - Rajeeb K Swain
- Institute of Life Sciences, Bhubaneswar, Odisha 751023, India
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Shrestha B, Tang L, Romero G. Nanoparticles‐Mediated Combination Therapies for Cancer Treatment. ADVANCED THERAPEUTICS 2019. [DOI: 10.1002/adtp.201900076] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Affiliation(s)
- Binita Shrestha
- Department of Biomedical Engineering University of Texas at San Antonio One UTSA Circle San Antonio TX 78249 USA
| | - Liang Tang
- Department of Biomedical Engineering University of Texas at San Antonio One UTSA Circle San Antonio TX 78249 USA
| | - Gabriela Romero
- Department of Chemical Engineering University of Texas at San Antonio One UTSA Circle San Antonio TX 78249 USA
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Nik ME, Momtazi-Borojeni AA, Zamani P, Navashenaq JG, Iranshahi M, Jaafari MR, Malaekeh-Nikouei B. Targeted-nanoliposomal combretastatin A4 (CA-4) as an efficient antivascular candidate in the metastatic cancer treatment. J Cell Physiol 2019; 234:14721-14733. [PMID: 30697744 DOI: 10.1002/jcp.28230] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2018] [Revised: 01/03/2019] [Accepted: 01/10/2019] [Indexed: 01/24/2023]
Abstract
A number of antiangiogenic drugs have been approved by the Food and Drug Administration which are used in cancer therapy, and variety of other agents in several stages of clinical development or in preclinical assessment. Among these, combretastatin A4 (CA-4) is an under-researched inhibitor of angiogenesis that shows potential activity in the treatment of advanced tumors with migration capacity. However, its clinical application has been limited due to poor water solubility, low bioavailability, rapid metabolism, and systemic elimination. During the last decade, numerous investigations have been done to overcome these problems by using different CA-4 delivery systems or developing produgs of CA-4 or its structural analogs. Nevertheless, these strategies could not be efficient out of the undesired side effects on normal tissues. Nanoliposomal CA-4 not only benefits from the advantage of using liposomal drugs as opposed to free drugs but also can accumulate in the tumor site via specific targeting ligands, which leads to efficient targeting and enhancement of bioavailability. To the best of our knowledge, we consider an important attempt to understand different factors that might influence the CA-4 loading and release pattern of liposomes and the consequent results in tumor therapy. In this review, we shed light on various studied liposomal CA-4 formulations showing application thereof in cancer treatment.
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Affiliation(s)
- Maryam Ebrahimi Nik
- Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.,Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Amir Abbas Momtazi-Borojeni
- Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.,Department of Medical Biotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Parvin Zamani
- Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.,Department of Medical Biotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Jamshid Gholizadeh Navashenaq
- Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran.,Department of Immunogenetic and Cell Culture, Immunology Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mehrdad Iranshahi
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mahmoud Reza Jaafari
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.,Department of Pharmaceutical Nanotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Bizhan Malaekeh-Nikouei
- Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
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Zhu J, Zhang J, Wang Y, Chen J, Li X, Liu X, Kong E, Su SB, Zhang Z. The Effect of Interleukin 38 on Inflammation-induced Corneal Neovascularization. Curr Mol Med 2019; 19:589-596. [PMID: 31244436 DOI: 10.2174/1566524019666190627122655] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2019] [Revised: 05/27/2019] [Accepted: 05/30/2019] [Indexed: 11/22/2022]
Abstract
BACKGROUND Angiogenesis is tightly linked to inflammation. Cytokines of interleukin 1 (IL-1) family are key mediators in modulating inflammatory responses. METHODS In this study, we examined the role of IL-38, a member of the IL-1 family, in mediating inflammation-induced angiogenesis. RESULTS The results showed that the angiogenesis was attenuated by topical administration of IL-38 to the injured corneas in a mouse model of alkali-induced corneal neovascularization (CNV). Further study showed that the expression of inflammatory cytokines TNF-α, IL-6, IL-8 and IL-1β was decreased in the IL-38-treated corneas. Moreover, the angiogenic activities including the proliferation, migration and tube formation of human retinal endothelial cells were reduced by IL-38 treatment in vitro. CONCLUSION The data indicate that IL-38 modulates inflammation-induced angiogenesis.
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Affiliation(s)
- Jiangli Zhu
- The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, 453000, China
| | - Jing Zhang
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, 510060, China
| | - Yan Wang
- Guangdong Science and Technology Library (Guangdong Institute of Scientific and Technical Information and Development Strategy), China
| | - Jianping Chen
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, 510060, China
| | - Xiaopeng Li
- The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, 453000, China
| | - Xiangling Liu
- The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, 453000, China
| | - Eryan Kong
- Institute of Psychiatry and Neuroscience, Xinxiang Medical University, Xinxiang, Henan, 453000, China
| | - Shao B Su
- The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, 453000, China.,State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, 510060, China
| | - Zhongjian Zhang
- Institute of Psychiatry and Neuroscience, Xinxiang Medical University, Xinxiang, Henan, 453000, China
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Hysi E, Fadhel MN, Moore MJ, Zalev J, Strohm EM, Kolios MC. Insights into photoacoustic speckle and applications in tumor characterization. PHOTOACOUSTICS 2019; 14:37-48. [PMID: 31080733 PMCID: PMC6505056 DOI: 10.1016/j.pacs.2019.02.002] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/29/2018] [Revised: 01/21/2019] [Accepted: 02/20/2019] [Indexed: 05/20/2023]
Abstract
In ultrasound imaging, fully-developed speckle arises from the spatiotemporal superposition of pressure waves backscattered by randomly distributed scatterers. Speckle appearance is affected by the imaging system characteristics (lateral and axial resolution) and the random-like nature of the underlying tissue structure. In this work, we examine speckle formation in acoustic-resolution photoacoustic (PA) imaging using simulations and experiments. Numerical and physical phantoms were constructed to demonstrate that PA speckle carries information related to unresolved absorber structure in a manner similar to ultrasound speckle and unresolved scattering structures. A fractal-based model of the tumor vasculature was used to study PA speckle from unresolved cylindrical vessels. We show that speckle characteristics and the frequency content of PA signals can be used to monitor changes in average vessel size, linked to tumor growth. Experimental validation on murine tumors demonstrates that PA speckle can be utilized to characterize the unresolved vasculature in acoustic-resolution photoacoustic imaging.
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Affiliation(s)
- Eno Hysi
- Department of Physics, Ryerson University, Toronto, ON, Canada
- Institute for Biomedical Engineering, Science and Technology, Li Ka Shing Knowledge Institute, Keenan Research Centre, St. Michael’s Hospital, Toronto, ON, Canada
| | - Muhannad N. Fadhel
- Department of Physics, Ryerson University, Toronto, ON, Canada
- Institute for Biomedical Engineering, Science and Technology, Li Ka Shing Knowledge Institute, Keenan Research Centre, St. Michael’s Hospital, Toronto, ON, Canada
| | - Michael J. Moore
- Department of Physics, Ryerson University, Toronto, ON, Canada
- Institute for Biomedical Engineering, Science and Technology, Li Ka Shing Knowledge Institute, Keenan Research Centre, St. Michael’s Hospital, Toronto, ON, Canada
| | - Jason Zalev
- Department of Physics, Ryerson University, Toronto, ON, Canada
- Institute for Biomedical Engineering, Science and Technology, Li Ka Shing Knowledge Institute, Keenan Research Centre, St. Michael’s Hospital, Toronto, ON, Canada
| | - Eric M. Strohm
- Department of Mechanical and Industrial Engineering, University of Toronto, Toronto, ON, Canada
- Translational Biology and Engineering Program, Ted Rogers Centre for Heart Research, Toronto, ON, Canada
| | - Michael C. Kolios
- Department of Physics, Ryerson University, Toronto, ON, Canada
- Institute for Biomedical Engineering, Science and Technology, Li Ka Shing Knowledge Institute, Keenan Research Centre, St. Michael’s Hospital, Toronto, ON, Canada
- Corresponding author.
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Alsultan AA, Barentsz MW, Smits MLJ, Koopman M, Lam MGEH, Rosenbaum CENM. Angiogenesis in 90Y-Radioembolization of Colorectal Liver Metastases. Semin Nucl Med 2019; 49:204-210. [PMID: 30954186 DOI: 10.1053/j.semnuclmed.2019.01.004] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
In order to evaluate the role of angiogenesis in 90Y-radioembolization for colorectal cancer liver metastasis an overview was provided of angiogenic growth factors and their function, the angiogenic mechanisms in colorectal cancer, the role of hypoxia, and the advances in antiangiogenic therapy. Last, the use of circulating angiogenic growth factors in 90Y-radioembolization was reviewed. Two literature searches were conducted. A search query in PubMed on angiogenesis in colorectal cancer, and a systematic search in PubMed (Medline), Embase, and the Cochrane Library (October 2018) with synonyms for "radioembolization" and "angiogenic growth factor." The first search yielded 3 relevant publications on the role of angiogenic growth factors in colorectal cancer, hypoxia, and antiangiogenic therapy. The second search yielded two prospective studies on circulating angiogenic factors and their relationship with response and survival after 90Y-radioembolization for colorectal cancer liver metastases. Rises in circulating angiogenic growth factors after radioembolization were seen in both studies. High baseline values of Ang-2 and IL-8 correlated with shorter survival and post 90Y-radiembolization rises in Ang-2 and HGF correlated with early progression. Various angiogenic growth factors play a role in the development and progression of colorectal cancer. Several factors show correlation with poor outcomes after 90Y-radioembolization and might be used for patient selection in the future, however, validation in larger comparative studies is required.
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Affiliation(s)
- Ahmed A Alsultan
- Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
| | - Maarten W Barentsz
- Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
| | - Maarten L J Smits
- Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
| | - Miriam Koopman
- Department of Medical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
| | - Marnix G E H Lam
- Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
| | - Charlotte E N M Rosenbaum
- Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
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Dual functions of STAT3 in LPS-induced angiogenesis of hepatocellular carcinoma. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH 2019; 1866:566-574. [DOI: 10.1016/j.bbamcr.2018.11.016] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/24/2018] [Revised: 11/22/2018] [Accepted: 11/30/2018] [Indexed: 12/12/2022]
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Dong P, Rakesh K, Manukumar H, Mohammed YHE, Karthik C, Sumathi S, Mallu P, Qin HL. Innovative nano-carriers in anticancer drug delivery-a comprehensive review. Bioorg Chem 2019; 85:325-336. [PMID: 30658232 DOI: 10.1016/j.bioorg.2019.01.019] [Citation(s) in RCA: 106] [Impact Index Per Article: 17.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2018] [Revised: 01/07/2019] [Accepted: 01/08/2019] [Indexed: 02/07/2023]
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