An Implantable Depot That Can Generate Oxygen in Situ for Overcoming Hypoxia-Induced Resistance to Anticancer Drugs in Chemotherapy

Huang, Chieh‐Cheng; Chia, Wei-Tso; Chung, Mei‐Ing; Lin, Kun-Ju; Hsiao, Chun-Wen; Jin, Chuan; Lim, Woon-Hui; Chen, Chun‐Chieh; Sung, Hsing‐Wen

doi:10.1021/jacs.6b01784

Cited by 327 publications

(209 citation statements)

References 17 publications

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“…170, 173, 176, 177 Specifically, oxygen-favoring PDT would deplete oxygenation level through photochemical consumption and occlusion of blood vessels. 146 Therefore, perfluorocarbon-integrated PDT with a continuous supply of molecular oxygen could be an innovative strategy to diminish the oxygen dependence.…”

Section: Oxygen Self-supplementmentioning

confidence: 99%

Reactive oxygen species generating systems meeting challenges of photodynamic cancer therapy

et al. 2016

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Reactive oxygen species (ROS)-mediated mechanism is the major cause underlying the efficacy of photodynamic therapy (PDT). The PDT procedure is based on the cascade of synergistic effects between light, photosensitizer (PS) and oxygen, which greatly favor the spatiotemporal control of the treatment. This procedure has also evoked several unresolved challenges at different levels including (i) limited penetration depth of light restricts traditional PDT to only superficial tumours; (ii) oxygen reliance deprives PDT treatment of hypoxic tumours; (iii) light could complicate the phototherapeutic outcomes due to the concurrent heat generation; (iv) specific delivery of PSs to sub-cellular organelles for exerting effective toxicity remains an issue; and (v) side effects by undesirable white-light activation and self-catalysation of traditional PSs. Recent advances in nanotechnology and nanomedicine have provided new opportunities to develop ROS-generating systems through photodynamic or non-photodynamic procedures while tackling the challenges of current PDT approaches. In this review, we summarize the current status and discuss the possible opportunities of ROS generation for cancer therapy. We hope this review will spur pre-clinical research and clinical practice for ROS-mediated tumour treatment.

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Section: Oxygen Self-supplementmentioning

confidence: 99%

Reactive oxygen species generating systems meeting challenges of photodynamic cancer therapy

et al. 2016

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“…Therefore, overcoming hypoxia can significantly potentiate chemotherapy. To that end, various systems aiming at raising oxygen tension at hypoxic solid tumors have been urgently pursued 7. Most of these studies, however, are still at the bench stage and far from being used as bedside applications.…”

Section: Introductionmentioning

confidence: 99%

Hyperbaric Oxygen Potentiates Doxil Antitumor Efficacy by Promoting Tumor Penetration and Sensitizing Cancer Cells

Zhu

Huang

et al. 2018

Advanced Science

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Hypoxia is a fundamental hallmark of solid tumors and helps contribute to chemotherapy resistance. Hyperbaric oxygen (HBO) therapy can overcome tumor hypoxia and promote chemotherapy antitumor efficacy; however, the simultaneous administration of some conventional chemotherapies, including doxorubicin (DOX), with HBO is considered an absolute contraindication. Here, DOX‐loaded liposome (Doxil) is coadministered with HBO to assess the safety and efficacy of this combination treatment. By overcoming tumor hypoxia, HBO not only improves Doxil tumor penetration by decreasing the collagen deposition but also sensitizes tumor cells to Doxil. As a result, the combination treatment synergistically inhibits H22 tumor growth, with a tumor inhibition rate of 91.5%. The combination of HBO with Doxil shows neither extra side effects nor promotion of tumor metastasis. These results collectively reveal that the combination of HBO with Doxil is an effective and safe treatment modality. As both HBO and Doxil are routinely used, their combination could quickly translate to clinical trials for patients with hypoxic solid tumors.

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“…Hypoxic states occur in tumors, including glioblastomas, when uncontrolled cell proliferation outpaces the available oxygen supply, leading to intratumoral necrosis23. Tumor hypoxia is associated with metastases4, recurrences5 and resistance to chemotherapy and radiation therapy678. These effects are mediated by a family of transcription factors called hypoxia-inducible factors 1α and 2α (Hif-1α and HIF-2α)9.…”

mentioning

confidence: 99%

Hypoxia induces H19 expression through direct and indirect Hif-1α activity, promoting oncogenic effects in glioblastoma

Nie

et al. 2017

Sci Rep

105

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H19 expression is elevated in many human tumors including glioblastomas, suggesting an oncogenic role for the long noncoding RNA; yet the upregulation of H19 in glioblastomas remains unclear. Here we report that hypoxia significantly stimulated H19 expression in glioblastoma cell lines, which was related to hypoxia-inducible factors 1α (Hif-1α). Hif-1α promoted H19 expression in U87 and U251 cells. Meanwhile PTEN is an advantageous factor to affect H19 expression, through attenuating Hif-1α stability. Hif-1α also positively correlates with H19 in human glioblastoma samples depending on PTEN status. ChIP and luciferase reporter assays showed that Hif-1α induced H19 transcription through directly binding to the H19 promoter. Furthermore, Hif-1α upregulated specific protein 1 (SP1) expression in glioblastomas cells in vitro and in vivo, and SP1 also strongly interacted with the H19 promoter to promote H19 expression under hypoxia. We also showed that H19 acts as a molecular sponge that binds miR-181d, relieving inhibition of β-catenin expression. Therefore, H19 participates in hypoxia-driven migration and invasion in glioblastoma cells. In summary, our results uncover the mechanisms that stimulate H19 expression under hypoxia to promote malignant effects in glioblastomas and suggest H19 might be a promising therapeutic target.

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An Implantable Depot That Can Generate Oxygen in Situ for Overcoming Hypoxia-Induced Resistance to Anticancer Drugs in Chemotherapy

Cited by 327 publications

References 17 publications

Reactive oxygen species generating systems meeting challenges of photodynamic cancer therapy

Reactive oxygen species generating systems meeting challenges of photodynamic cancer therapy

Hyperbaric Oxygen Potentiates Doxil Antitumor Efficacy by Promoting Tumor Penetration and Sensitizing Cancer Cells

Hypoxia induces H19 expression through direct and indirect Hif-1α activity, promoting oncogenic effects in glioblastoma

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