Therapeutic Delivery of siRNA Silencing HIF-1 Alpha with Micellar Nanoparticles Inhibits Hypoxic Tumor Growth

2012 ◽  
Vol 9 (10) ◽  
pp. 2863-2874 ◽  
Author(s):  
Xi-Qiu Liu ◽  
Meng-Hua Xiong ◽  
Xiao-Ting Shu ◽  
Rui-Zhi Tang ◽  
Jun Wang
Keyword(s):  
Tumor Growth ◽  
Therapeutic Delivery ◽  
Hypoxic Tumor ◽  
Sirna Silencing ◽  
Micellar Nanoparticles

scholarly journals Tumor-Associated Macrophages and Their Functional Transformation in the Hypoxic Tumor Microenvironment

2021 ◽  
Vol 12 ◽  
Author(s):  
Zicong He ◽  
Shuixing Zhang
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Growth ◽  
Tumor Associated Macrophages ◽  
Mediate Immune Response ◽  
Functional Transformation ◽  
Functional Differences ◽  
Inflammatory Phenotype ◽  
Internal Mechanism ◽  
Hypoxic Tumor ◽  
Early Phases

Tumor-associated macrophages (TAMs) are some of the most abundant immune cells within tumors and perform a broad repertoire of functions via diverse phenotypes. On the basis of their functional differences in tumor growth, TAMs are usually categorized into two subsets of M1 and M2. It is well established that the tumor microenvironment (TME) is characterized by hypoxia along with tumor progression. TAMs adopt an M1-like pro-inflammatory phenotype at the early phases of oncogenesis and mediate immune response that inhibits tumor growth. As tumors progress, anabatic hypoxia of the TME gradually induces the M2-like functional transformation of TAMs by means of direct effects, metabolic influence, lactic acidosis, angiogenesis, remodeled stroma, and then urges them to participate in immunosuppression, angiogenesis and other tumor-supporting procedure. Therefore, thorough comprehension of internal mechanism of this TAM functional transformation in the hypoxic TME is of the essence, and might provide some novel insights in hypoxic tumor immunotherapeutic strategies.

Anti-EGFR lipid micellar nanoparticles co-encapsulating quantum dots and paclitaxel for tumor-targeted theranosis

Nanoscale ◽  
2018 ◽  
Vol 10 (41) ◽  
pp. 19338-19350 ◽  
Author(s):  
Seong Jae Kang ◽  
Hwa Yeon Jeong ◽  
Min Woo Kim ◽  
In Ho Jeong ◽  
Moon Jung Choi ◽  
...  
Keyword(s):  
Quantum Dots ◽  
Tumor Growth ◽  
Tumor Imaging ◽  
Theranostic Nanoparticles ◽  
Inhibition Of Tumor Growth ◽  
Micellar Nanoparticles

Tumor-targeted theranostic nanoparticles prepared by considering nano-bio interactions exhibited improved tumor imaging and efficient inhibition of tumor growth.

Systemic delivery of axitinib with nanohybrid liposomal nanoparticles inhibits hypoxic tumor growth

2015 ◽  
Vol 3 (3) ◽  
pp. 408-416 ◽  
Author(s):  
Ju Yeon Choi ◽  
Thiruganesh Ramasamy ◽  
Tuan Hiep Tran ◽  
Sae Kwang Ku ◽  
Beom Soo Shin ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Systemic Delivery ◽  
Hypoxic Tumor ◽  
Liposomal Nanoparticles

Hybrid liposomal nanoparticles for systemic delivery of axitinib inhibit hypoxic tumor growth.

scholarly journals WITHDRAWN: Modified delivery of axitinib loaded nanohybrid liposomal nanoparticles for hypoxic tumor growth

2015 ◽  
Author(s):  
Ju Yeon Choi ◽  
Ramasamya Thiruganesh ◽  
Tran Tuan Hiep ◽  
Raj Kumar Thapa ◽  
Dong Shik Kim ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Hypoxic Tumor ◽  
Liposomal Nanoparticles

scholarly journals Mechanisms of vasculogenic mimicry in hypoxic tumor microenvironments

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Xiaoxu Wei ◽  
Yunhua Chen ◽  
Xianjie Jiang ◽  
Miao Peng ◽  
Yiduo Liu ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Malignant Tumors ◽  
Vasculogenic Mimicry ◽  
Main Body ◽  
Differentiation Potential ◽  
Ecm Remodeling ◽  
Tumor Microenvironments ◽  
Hypoxic Environment ◽  
Hypoxic Tumor ◽  
Aggressive Tumors

Abstract Background Vasculogenic mimicry (VM) is a recently discovered angiogenetic process found in many malignant tumors, and is different from the traditional angiogenetic process involving vascular endothelium. It involves the formation of microvascular channels composed of tumor cells; therefore, VM is considered a new model for the formation of new blood vessels in aggressive tumors, and can provide blood supply for tumor growth. Many studies have pointed out that in recent years, some clinical treatments against angiogenesis have not been satisfactory possibly due to the activation of VM. Although the mechanisms underlying VM have not been fully elucidated, increasing research on the soil “microenvironment” for tumor growth suggests that the initial hypoxic environment in solid tumors is inseparable from VM. Main body In this review, we describe that the stemness and differentiation potential of cancer stem cells are enhanced under hypoxic microenvironments, through hypoxia-induced epithelial-endothelial transition (EET) and extracellular matrix (ECM) remodeling to form the specific mechanism of vasculogenic mimicry; we also summarized some of the current drugs targeting VM through these processes, suggesting a new reference for the clinical treatment of tumor angiogenesis. Conclusion Overall, the use of VM inhibitors in combination with conventional anti-angiogenesis treatments is a promising strategy for improving the effectiveness of targeted angiogenesis treatments; further, considering the importance of hypoxia in tumor invasion and metastasis, drugs targeting the hypoxia signaling pathway seem to achieve good results.

scholarly journals Activation of Chaperon-Mediated Autophagy Via Modulation of Hsp90 Activity Inhibits Tumor Growth Under Hypoxia

2021 ◽  
Author(s):  
Jun-Kyu Byun ◽  
Sun Hee Lee ◽  
Eui Jung Moon ◽  
Myo-Hyeon Park ◽  
Hyeonha Jang ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Tumor Progression ◽  
Cell Biology ◽  
Chaperone Function ◽  
Depth Analysis ◽  
Hsp90 Chaperone ◽  
Hypoxic Tumor

Abstract Background: Chaperon-mediated autophagy (CMA) is a target specific degradation pathway among autophagic processes. Although CMA plays critical roles in tumor progression in general, the role of CMA in tumor progression under hypoxia is poorly understood. We investigated the role of CMA in hypoxic tumor using a novel Hsp90-mediated modulator of CMA.Methods: We examined whether manassantin A (ManA), known as a potent inhibitor of HIF-1α, is a CMA modulator using biochemical, molecular, and cell biology approaches. We analyzed the effects of ManA on Hsp90 chaperone function by using Significant Analysis of Microarray, luciferase refolding assay, HS-10 resin binding assay, NMR spectroscopy, and SPR assay. We investigated tumor growth in response to monotherapy and combination therapy with ManA and anti-programmed death-1 (PD-1) antibody in vivo. To assess the clinical efficacy of CMA-related genes, we analyzed the gene expressions of HIF-1α, HSP90AA1, and transcription factor EB (TFEB) using TCGA datasets. Finally, we assessed in vivo/in vitro absorption, distribution, metabolism, and excretion properties of ManA.Results: ManA inhibits Hsp90 chaperone function through disruption of the Hsp90/F1F0-ATP synthase (chaperone/co-chaperone) complex. The inhibition of Hsp90 enhances the interaction of CMA substrates and LAMP-2A as well as TFEB nuclear localization, thus leading to CMA activation. Importantly, CMA activation not only retards tumor growth in vitro and in vivo, but also displays cooperative antitumor activity with anti-PD-1 antibody in vivo. An in-depth analysis of TCGA datasets shows that combined expression of HSP90AA1High/HIF1AHigh or TFEBLow/HIF1AHigh is strongly correlated with poor prognosis in lung cancer patients. Conclusions: ManA-induced inhibition of Hsp90 promotes CMA activity and decreases the stability of CMA substrates such as HIF-1α protein, leading to a marked reduction of hypoxic tumor growth. Therefore, targeting CMA activity via Hsp90 may present a promising therapeutic strategy for hypoxic tumor.

M2 polarization of macrophages by Oncostatin M in hypoxic tumor microenvironment is mediated by mTORC2 and promotes tumor growth and metastasis

Cytokine ◽  
2019 ◽  
Vol 118 ◽  
pp. 130-143 ◽  
Author(s):  
Richa Shrivastava ◽  
Mohammad Asif ◽  
Varsha Singh ◽  
Parul Dubey ◽  
Showkat Ahmad Malik ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Growth ◽  
Oncostatin M ◽  
M2 Polarization ◽  
Hypoxic Tumor ◽  
Tumor Growth And Metastasis
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