Direct measurement of hypoxia in a xenograft multiple myeloma model by optical-resolution photoacoustic microscopy

Imai, Toru; Muz, Barbara; Yeh, Cheng-Hung; Yao, Junjie; Zhang, Ruiying; Azab, Abdel Kareem; Wang, Lihong

doi:10.1080/15384047.2016.1276137

Cited by 19 publications

(21 citation statements)

References 17 publications

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“…We have previously shown that regions of hypoxia arise in MM [19], likely due to tumor overgrowth coupled with insufficient angiogenesis, or dysfunctional blood vessels [32]. Hypoxia-inducible factor-1α (HIF-1α), a key transcription factor, plays a major role in cellular hypoxic response by inducing gene expression affecting cancer cell adaptive responses [33], hence it is frequently used as an intrinsic marker of hypoxia.…”

Section: Discussionmentioning

confidence: 99%

Tariquidar sensitizes multiple myeloma cells to proteasome inhibitors via reduction of hypoxia-induced P-gp-mediated drug resistance

Muz

Kusdono

Azab

et al. 2017

Leukemia & Lymphoma

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Multiple myeloma (MM) presents a poor prognosis and high lethality of patients due to development of drug resistance. P-glycoprotein (P-gp), a drug-efflux transporter, is upregulated in MM patients post-chemotherapy and is involved in the development of drug resistance since many anti-myeloma drugs (including proteasome inhibitors) are P-gp substrates. Hypoxia develops in the bone marrow niche during MM progression and has long been linked to chemoresistance. Additionally, hypoxia-inducible transcription factor (HIF-1α) was demonstrated to directly regulate P-gp expression. We found that in MM patients P-gp expression positively correlated with the hypoxic marker, HIF-1α. Hypoxia increased P-gp protein expression and its efflux capabilities in MM cells in vitro using flow cytometry. We reported herein that hypoxia-mediated resistance to carfilzomib and bortezomib in MM cells is due to P-gp activity and was reversed by tariquidar, a P-gp inhibitor. These results suggest combining proteasome inhibitors with P-gp inhibition for future clinical studies.

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Section: Discussionmentioning

confidence: 99%

Tariquidar sensitizes multiple myeloma cells to proteasome inhibitors via reduction of hypoxia-induced P-gp-mediated drug resistance

Muz

Kusdono

Azab

et al. 2017

Leukemia & Lymphoma

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“…To achieve automatic detection of tumors based on our finding, we developed a novel framework based on pattern recognition algorithms, and achieved a tumor identification accuracy of 82.67%. We expect that this new discovery will find more applications, such as tracing sO 2 -based biomarkers in internal organs [7] and the brain in humans [23].…”

Section: Discussionmentioning

confidence: 99%

Early-stage tumor detection using photoacoustic microscopy: a pattern recognition approach

Yeh

Wang

Liang

et al. 2017

Photons Plus Ultrasound: Imaging and Sensing 2017

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We report photoacoustic microscopy (PAM) of arteriovenous (AV) shunts in early stage tumors in vivo, and develop a pattern recognition framework for computerized tumor detection. Here, using a high-resolution photoacoustic microscope, we implement a new blood oxygenation (sO 2 )-based disease marker induced by the AV shunt effect in tumor angiogenesis. We discovered a striking biological phenomenon: There can be two dramatically different sO 2 values in bloodstreams flowing side-by-side in a single vessel. By tracing abnormal sO 2 values in the blood vessels, we can identify a tumor region at an early stage. To further automate tumor detection based on our findings, we adopt widely used pattern recognition methods and develop an efficient computerized classification framework. The test result shows over 80% averaged detection accuracy with false positive contributing 18.52% of error test samples on a 50 PAM image dataset.

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“…Optoacoustic imaging combines imaging of optical contrast with ultrasound resolution. Besides macroscopic imaging of cancer biology in vivo in preclinical models of disease, novel optoacoustic systems are operating at the mesoscopic or microscopic scale [22, 23], which permit studying direct interactions between tumor cells, the tumor microenvironment and tumor vasculature. Label-free detection using intrinsic signalling properties is favourable over cumbersome additional labelling or additional injection of a specific imaging probe.…”

Section: Discussionmentioning

confidence: 99%

Optoacoustic properties of Doxorubicin – A pilot study

et al. 2019

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Doxorubicin (DOX) is a widely used chemotherapeutic anticancer drug. Its intrinsic fluorescence properties enable investigation of tumor response, drug distribution and metabolism. First phantom studies in vitro showed optoacoustic property of DOX. We therefore aimed to further investigate the optoacoustic properties of DOX in biological tissue in order to explore its potential as theranostic agent. We analysed doxorubicin hydrochloride (Dox·HCl) and liposomal encapsulated doxorubicin hydrochloride (Dox·Lipo), two common drugs for anti-cancer treatment in clinical medicine. Optoacoustic measurements revealed a strong signal of both doxorubicin substrates at 488 nm excitation wavelength. Post mortem analysis of intra-tumoral injections of DOX revealed a detectable optoacoustic signal even at three days after the injection. We thereby demonstrate the general feasibility of doxorubicin detection in biological tissue by means of optoacoustic tomography, which could be applied for high resolution imaging at mesoscopic depths dictated by effective penetration of visible light into the biological tissues.

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Direct measurement of hypoxia in a xenograft multiple myeloma model by optical-resolution photoacoustic microscopy

Cited by 19 publications

References 17 publications

Tariquidar sensitizes multiple myeloma cells to proteasome inhibitors via reduction of hypoxia-induced P-gp-mediated drug resistance

Tariquidar sensitizes multiple myeloma cells to proteasome inhibitors via reduction of hypoxia-induced P-gp-mediated drug resistance

Early-stage tumor detection using photoacoustic microscopy: a pattern recognition approach

Optoacoustic properties of Doxorubicin – A pilot study

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