Author
Shinae Kizaka-Kondoh
Other affiliations: Kyoto University
Bio: Shinae Kizaka-Kondoh is an academic researcher from Tokyo Institute of Technology. The author has contributed to research in topics: Tumor hypoxia & Bioluminescence imaging. The author has an hindex of 36, co-authored 102 publications receiving 4399 citations. Previous affiliations of Shinae Kizaka-Kondoh include Kyoto University.
Papers published on a yearly basis
Papers
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TL;DR: Progress is described on the biological aspects of tumor hypoxia and a compilation of the recent molecular approaches used to target hypoxic tumors is provided, including a work with a unique Hypoxia‐targeting protein drug, TOP3, with which to address the above three difficulties.
Abstract: Tumor hypoxia has been considered to be a potential therapeutic problem because it renders solid tumors more resistant to sparsely ionizing radiation (IR) and chemotherapeutic drugs Moreover, recent laboratory and clinical data have shown that tumor hypoxia is also associated with a more malignant phenotype and poor survival in patients suffering from various solid tumors Therefore, selective targeting of hypoxic tumor cells has been explored, and since severe hypoxia (pO(2) < 033%, 25 mmHg) does not occur in normal tissue, tumor hypoxia could be exploited for therapeutic advantage However, the following three characteristics of hypoxic tumor regions present obstacles in targeting hypoxic cells First, it is difficult to deliver a sufficient amount of drug to a region that is remote from blood vessels Second, one must specifically target hypoxic tumor cells while sparing normal well-oxygenated tissue from damage Finally, the severely hypoxic tumor cells to be attacked have often stopped dividing Therefore, high delivery efficiency, high specificity and selective cytotoxicity are all necessary to target and combat hypoxic tumor cells The current review describes progress on the biological aspects of tumor hypoxia and provides a compilation of the recent molecular approaches used to target hypoxic tumors These approaches include our work with a unique hypoxia-targeting protein drug, TOP3, with which we have sought to address the above three difficulties
339 citations
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TL;DR: AkaBLI produced emissions in vivo that were brighter by a factor of 100 to 1000 than conventional systems, allowing noninvasive visualization of single cells deep inside freely moving animals, and is therefore a bioengineered light source to spur unprecedented scientific, medical, and industrial applications.
Abstract: Bioluminescence is a natural light source based on luciferase catalysis of its substrate luciferin. We performed directed evolution on firefly luciferase using a red-shifted and highly deliverable luciferin analog to establish AkaBLI, an all-engineered bioluminescence in vivo imaging system. AkaBLI produced emissions in vivo that were brighter by a factor of 100 to 1000 than conventional systems, allowing noninvasive visualization of single cells deep inside freely moving animals. Single tumorigenic cells trapped in the mouse lung vasculature could be visualized. In the mouse brain, genetic labeling with neural activity sensors allowed tracking of small clusters of hippocampal neurons activated by novel environments. In a marmoset, we recorded video-rate bioluminescence from neurons in the striatum, a deep brain area, for more than 1 year. AkaBLI is therefore a bioengineered light source to spur unprecedented scientific, medical, and industrial applications.
275 citations
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TL;DR: Tumor-associated hypoxia and HIF-1 expression promote the progression of bone metastases in breast cancer by suppressing osteoblast differentiation and promoting osteoclastogenesis.
Abstract: Hypoxia is a common feature of solid tumors and is associated with their malignant phenotype. The transcription factor hypoxia-inducible factor-1 (HIF-1) is a major regulator of adaptation to hypoxia and is implicated in the malignant progression of cancers. Here, we studied whether hypoxia and HIF-1 expression contribute to the development of bone metastases using a well-characterized animal model of bone metastasis in MDA-MB-231 human breast cancer cells. To study the role of hypoxia in bone metastases, we tested the effects of the fusion protein (TOP3), the oxygen-dependent degradation domain of HIF-1alpha fused with HIV-TAT, and procaspase-3. TOP3 selectively induced apoptosis in hypoxic tumor cells in vitro and significantly reduced bone metastases in vivo. We next examined the role of HIF-1 in bone metastases by establishing MDA-MB-231 cells overexpressing constitutively active or dominant-negative HIF-1alpha (MDA/CA-HIF or MDA/DN-HIF, respectively). Bone metastases of MDA/CA-HIF were significantly increased with elevated number of CD31-positive blood vessels. In contrast, bone metastases were significantly reduced in MDA/DN-HIF. Because the progression of osteolytic bone metastases is due in part to the imbalance between bone formation and bone resorption, we examined the effects of hypoxia and HIF-1 on the differentiation of osteoblasts and osteoclasts. Hypoxia and CA-HIF overexpression markedly inhibited osteoblastic differentiation, whereas hypoxia increased osteoclast-like cell formation. In conclusion, these results suggest that tumor-associated hypoxia and HIF-1 expression promote the progression of bone metastases in breast cancer. Our results also suggest that hypoxia and HIF-1 lead to the development of osteolytic bone metastases by suppressing osteoblast differentiation and promoting osteoclastogenesis.
227 citations
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TL;DR: It is concluded that the NO donor NOC18 induces Hif-1α synthesis under conditions of NO formation during normoxia and that hydroxylation of HIF-1 α is not regulated by NOC 18.
204 citations
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TL;DR: The significance of pimonidazole and HIF‐1 as exogenous and endogenous hypoxia markers, respectively, as well as their evaluation and imaging of tumorHypoxia are discussed, particularly in the therapy against refractory cancers.
Abstract: A tumor-specific microenvironment is characterized by hypoxia, in which oxygen tension is considerably lower than in normal tissues. The hypoxic status of various solid tumors has been attributed as an indicator of adverse prognosis due to tumor progression toward a more malignant phenotype with increased metastatic potential and resistance to treatment. Various exogenous and endogenous markers for hypoxia are currently available and studied in relation to each other, tumor architecture, and tumor microenvironment. Over the last few decades, various methods have been suggested to assess the level of oxygenation in solid tumors. Among them, nitroimidazole compounds have provided promising information on tumor hypoxia. To quantify the extent of hypoxia requires that nitroimidazole binding be primarily dependent on oxygen concentration as well as nitroreductase levels in the tumor cells. Furthermore, recent progress in molecular biology has highlighted a transcription factor, hypoxia-inducible factor (HIF)-1, whose activity is induced by hypoxia. HIF-1 plays a central role in malignant progression by inducing the expression of various genes, whose functions are strongly associated with malignant alteration of the entire tumor. The cellular changes induced by HIF-1 are extremely important therapeutic targets of cancer therapy, particularly in the therapy against refractory cancers. In this review, we will discuss the significance of pimonidazole and HIF-1 as exogenous and endogenous hypoxia markers, respectively, as well as their evaluation and imaging of tumor hypoxia.
203 citations
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TL;DR: There is, I think, something ethereal about i —the square root of minus one, which seems an odd beast at that time—an intruder hovering on the edge of reality.
Abstract: There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality.
Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …
33,785 citations
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TL;DR: Therapeutic success in targeting these protumoral roles in preclinical models and in early clinical trials suggests that macrophages are attractive targets as part of combination therapy in cancer treatment.
2,945 citations
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TL;DR: The two main approaches, namely bioreductive prodrugs and inhibitors of molecular targets upon which hypoxic cell survival depends are reviewed, and the particular challenges and opportunities these overlapping strategies present are addressed.
Abstract: Hypoxia is a feature of most tumours, albeit with variable incidence and severity within a given patient population. It is a negative prognostic and predictive factor owing to its multiple contributions to chemoresistance, radioresistance, angiogenesis, vasculogenesis, invasiveness, metastasis, resistance to cell death, altered metabolism and genomic instability. Given its central role in tumour progression and resistance to therapy, tumour hypoxia might well be considered the best validated target that has yet to be exploited in oncology. However, despite an explosion of information on hypoxia, there are still major questions to be addressed if the long-standing goal of exploiting tumour hypoxia is to be realized. Here, we review the two main approaches, namely bioreductive prodrugs and inhibitors of molecular targets upon which hypoxic cell survival depends. We address the particular challenges and opportunities these overlapping strategies present, and discuss the central importance of emerging diagnostic tools for patient stratification in targeting hypoxia.
2,570 citations
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TL;DR: The main focus in MUCKE is on cleaning large scale Web image corpora and on proposing image representations which are closer to the human interpretation of images.
Abstract: MUCKE aims to mine a large volume of images, to structure them conceptually and to use this conceptual structuring in order to improve large-scale image retrieval. The last decade witnessed important progress concerning low-level image representations. However, there are a number problems which need to be solved in order to unleash the full potential of image mining in applications. The central problem with low-level representations is the mismatch between them and the human interpretation of image content. This problem can be instantiated, for instance, by the incapability of existing descriptors to capture spatial relationships between the concepts represented or by their incapability to convey an explanation of why two images are similar in a content-based image retrieval framework. We start by assessing existing local descriptors for image classification and by proposing to use co-occurrence matrices to better capture spatial relationships in images. The main focus in MUCKE is on cleaning large scale Web image corpora and on proposing image representations which are closer to the human interpretation of images. Consequently, we introduce methods which tackle these two problems and compare results to state of the art methods. Note: some aspects of this deliverable are withheld at this time as they are pending review. Please contact the authors for a preview.
2,134 citations
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TL;DR: This Review covers recent progress on near-infrared fluorescence imaging for preclinical animal studies and clinical diagnostics and interventions.
Abstract: This Review covers recent progress on near-infrared fluorescence imaging for preclinical animal studies and clinical diagnostics and interventions.
1,774 citations