Tumor-targeting <i>Salmonella typhimurium</i> A1-R decoys quiescent cancer cells to cycle as visualized by FUCCI imaging and become sensitive to chemotherapy

Yano, Shuya; Zhang, Yong; Zhao, Ming; Hiroshima, Yukihiko; Miwa, Shinji; Uehara, Fuminari; Kishimoto, Hiroyuki; Tazawa, Hiroshi; Bouvet, Michael; Fujiwara, Toshiyoshi; Hoffman, Robert M.

doi:10.4161/15384101.2014.964115

Cited by 96 publications

(91 citation statements)

References 32 publications

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“…This blocked much of the NIR light, which can explain why there is overall less cell damage in the TPM experiments compared to the two-channel fiber bundle results, as seen in H&E stained samples. In future, with cell-cycle responsible fluorescent protein labelled tumor cells [29-31], it may be possible to simultaneously monitor cell death and APCs microdistribution in real time in living mice.…”

Section: Discussionmentioning

confidence: 99%

Real-time monitoring of microdistribution of antibody-photon absorber conjugates during photoimmunotherapy in vivo

Tang

Nagaya

Liu

et al. 2017

Journal of Controlled Release

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Photoimmunotherapy (PIT) is an emerging low side effect cancer therapy based on a monoclonal antibody (mAb) conjugated with a near-infrared (NIR) phthalocyanine dye IRDye 700DX. IR700 is fluorescent, can be used as an imaging agent, and also is phototoxic. It induces rapid cell death after exposure to NIR light. PIT induces highly selective cancer cell death, while leaving most of tumor blood vessels unharmed, leading to an effect called super-enhanced permeability and retention (SUPR). SUPR significantly improves the effectiveness of the anticancer drug. Currently, the therapeutic effects of PIT are monitored using the IR700 fluorescent signal based on macroscopic fluorescence reflectance imagery. This technique, however, lacks the resolution and depth information to reveal the intratumor heterogeneity of mAb-IR700 distribution. We applied a minimally invasive two-channel fluorescence fiber imaging system by combining the traditional fluorescence imaging microscope with two imaging fiber bundles (~0.85 mm). This method monitored mAb-IR700 distribution and therapeutic effects during PIT at different intratumor locations (e.g., tumor surface vs. deep tumor) in situ and in real time simultaneously. This enabled evaluation of the therapeutic effects in vivo and treatment regimens. The average IR700 fluorescence intensity recovery after PIT to the tumor surface is 91.50%, while it is 100.63% in deep tumors. To verify the results, two-photon microscopy combined with a microprism was also used to record the mAb-IR700 distribution and fluorescence intensity of green fluorescent protein (GFP) at different tumor depths during PIT. After PIT treatment, there was significantly higher IR700 fluorescence recovery in deep tumor than in the tumor surface. This phenomenon can be explained by increased vascular permeability immediately after NIR-PIT. Fluorescence intensity of GFP at the tumor surface decreased significantly more compared to that of deep tumor and in controls (no PIT).

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Section: Discussionmentioning

confidence: 99%

Real-time monitoring of microdistribution of antibody-photon absorber conjugates during photoimmunotherapy in vivo

Tang

Nagaya

Liu

et al. 2017

Journal of Controlled Release

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“…Toward this goal, our laboratory developed tumor-targeting Salmonella typhimurium A1-R (S. typhimurium A1-R). S. typhimurium A1-R was effective against primary and metastatic tumors as monotherapy in nude mouse models of major cancers, including prostate, 22,23 breast, [24][25][26] lung, 27,28 pancreatic, 1,[29][30][31][32] ovarian, 33,34 stomach, 35 and cervical cancer. 36 In addition, S. typhimurium A1-R was effective against patientderived orthotopic models (PDOX) of pancreatic cancer, 1,32 sarcoma, 13,15,37 and melanoma.…”

Section: Introductionmentioning

confidence: 99%

Intra-arterial administration of tumor-targetingSalmonella typhimuriumA1-R regresses a cisplatin-resistant relapsed osteosarcoma in a patient-derived orthotopic xenograft (PDOX) mouse model

et al. 2017

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Previously, a patient-derived orthotopic xenograft (PDOX) model was established with a lung metastasis from an osteosarcoma patient which developed after adjuvant cisplatinum (CDDP) treatment. In this model, we previously demonstrated the efficacy of trabectedin (TRAB) and temozolomide (TEM) compared with CDDP. In the present report, osteosarcoma tissue was implanted orthotopically in the distal femur of mice which were randomized into the following groups when tumor volume reached approximately 100 mm 3 ; On day 14 after initiation of treatment, all but CDDP significantly inhibited tumor volume growth compared with untreated controls. Control (G1

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“…We previously reported viral-induced 4 or bacteria-induced decoy 5 of quiescent cancer cells within the tumor from G 0 /G 1 phase to S/ G 2 phase, which converts them to chemosensitivity. FUCCIexpressing tumors in ND-GFP transgenic nude mice were first treated with telomerase-dependent adenovirus OBP-301.…”

Section: Decoy Therapy Reduces Tumor Angiogenesismentioning

confidence: 99%

Cell-cycle-dependent drug-resistant quiescent cancer cells induce tumor angiogenesis after chemotherapy as visualized by real-time FUCCI imaging

et al. 2017

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We previously demonstrated that quiescent cancer cells in a tumor are resistant to conventional chemotherapy as visualized with a fluorescence ubiquitination cell cycle indicator (FUCCI). We also showed that proliferating cancer cells exist in a tumor only near nascent vessels or on the tumor surface as visualized with FUCCI and green fluorescent protein (GFP)-expressing tumor vessels. In the present study, we show the relationship between cellcycle phase and chemotherapy-induced tumor angiogenesis using in vivo FUCCI real-time imaging of the cell cycle and nestin-driven GFP to detect nascent blood vessels. We observed that chemotherapy-treated tumors, consisting of mostly of quiescent cancer cells after treatment, had much more and deeper tumor vessels than untreated tumors. These newly-vascularized cancer cells regrew rapidly after chemotherapy. In contrast, formerly quiescent cancer cells decoyed to S/G 2 phase by a telomerase-dependent adenovirus did not induce tumor angiogenesis. The present results further demonstrate the importance of the cancer-cell position in the cell cycle in order that chemotherapy be effective and not have the opposite effect of stimulating tumor angiogenesis and progression.

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Tumor-targeting Salmonella typhimurium A1-R decoys quiescent cancer cells to cycle as visualized by FUCCI imaging and become sensitive to chemotherapy

Cited by 96 publications

References 32 publications

Real-time monitoring of microdistribution of antibody-photon absorber conjugates during photoimmunotherapy in vivo

Real-time monitoring of microdistribution of antibody-photon absorber conjugates during photoimmunotherapy in vivo

Intra-arterial administration of tumor-targetingSalmonella typhimuriumA1-R regresses a cisplatin-resistant relapsed osteosarcoma in a patient-derived orthotopic xenograft (PDOX) mouse model

Cell-cycle-dependent drug-resistant quiescent cancer cells induce tumor angiogenesis after chemotherapy as visualized by real-time FUCCI imaging

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