565 results on '"Yano, Shuya"'
Search Results
2. Circulating cell-free DNA methylation patterns as non-invasive biomarkers to monitor colorectal cancer treatment efficacy without referencing primary site mutation profiles
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Yasui, Kazuya, Toshima, Toshiaki, Inada, Ryo, Umeda, Yuzo, Yano, Shuya, Tanioka, Hiroaki, Nyuya, Akihiro, Fujiwara, Toshiyoshi, Yamada, Takeshi, Naomoto, Yoshio, Goel, Ajay, and Nagasaka, Takeshi
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- 2024
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3. ADAR1 is a promising risk stratification biomarker of remnant liver recurrence after hepatic metastasectomy for colorectal cancer
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Hata, Nanako, Shigeyasu, Kunitoshi, Umeda, Yuzo, Yano, Shuya, Takeda, Sho, Yoshida, Kazuhiro, Fuji, Tomokazu, Yoshida, Ryuichi, Yasui, Kazuya, Umeda, Hibiki, Takahashi, Toshiaki, Kondo, Yoshitaka, Kishimoto, Hiroyuki, Mori, Yoshiko, Teraishi, Fuminori, Yamamoto, Hideki, Michiue, Hiroyuki, Nakamura, Keiichiro, Tazawa, Hiroshi, and Fujiwara, Toshiyoshi
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- 2023
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4. Regulatory T cells induce a suppressive immune milieu and promote lymph node metastasis in intrahepatic cholangiocarcinoma
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Konishi, Daisuke, Umeda, Yuzo, Yoshida, Kazuhiro, Shigeyasu, Kunitoshi, Yano, Shuya, Toji, Tomohiro, Takeda, Sho, Yoshida, Ryuichi, Yasui, Kazuya, Fuji, Tomokazu, Matsumoto, Kazuyuki, Kishimoto, Hiroyuki, Michiue, Hiroyuki, Teraishi, Fuminori, Kato, Hironari, Tazawa, Hiroshi, Yanai, Hiroyuki, Yagi, Takahito, Goel, Ajay, and Fujiwara, Toshiyoshi
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- 2022
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5. RNA editing facilitates the enhanced production of neoantigens during the simultaneous administration of oxaliplatin and radiotherapy in colorectal cancer
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Komatsu, Yasuhiro, Shigeyasu, Kunitoshi, Yano, Shuya, Takeda, Sho, Takahashi, Kazutaka, Hata, Nanako, Umeda, Hibiki, Yoshida, Kazuhiro, Mori, Yoshiko, Yasui, Kazuya, Yoshida, Ryuichi, Kondo, Yoshitaka, Kishimoto, Hiroyuki, Teraishi, Fuminori, Umeda, Yuzo, Kagawa, Shunsuke, Michiue, Hiroyuki, Tazawa, Hiroshi, Goel, Ajay, and Fujiwara, Toshiyoshi
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- 2022
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6. Prognostic factors for gastric cancer patients aged ≥ 85 years
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Endo, Shunji, primary, Higashida, Masaharu, additional, Furuya, Kei, additional, Yano, Shuya, additional, Okada, Toshimasa, additional, Yoshimatsu, Kazuhiko, additional, Fujiwara, Yoshinori, additional, and Ueno, Tomio, additional
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- 2024
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7. Tumor-targeting adenovirus OBP-401 inhibits primary and metastatic tumor growth of triple-negative breast cancer in orthotopic nude-mouse models
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Yano, Shuya, Takehara, Kiyoto, Kishimoto, Hiroyuki, Tazawa, Hiroshi, Urata, Yasuo, Kagawa, Shunsuke, Bouvet, Michael, Fujiwara, Toshiyoshi, and Hoffman, Robert M
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Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Cancer ,Breast Cancer ,2.1 Biological and endogenous factors ,Aetiology ,Adenoviridae ,Animals ,Cell Line ,Tumor ,Disease Models ,Animal ,Female ,Humans ,Mammary Glands ,Animal ,Mice ,Mice ,Nude ,Neoplasm Metastasis ,Oncolytic Virotherapy ,Organ Specificity ,Telomerase ,Triple Negative Breast Neoplasms ,Xenograft Model Antitumor Assays ,GFP ,green fluorescent protein ,RFP ,red fluorescent protein ,OBP-401 ,TNBC ,adenovirus ,high-metastatic ,nude mouse ,triple-negative breast cancer ,variants ,Oncology and carcinogenesis - Abstract
Our laboratory previously developed a highly-invasive, triple-negative breast cancer (TNBC) variant using serial orthotopic implantation of the human MDA-MB-231 cell line in nude mice. The isolated variant was highly-invasive in the mammary gland and lymphatic channels and metastasized to lymph nodes in 10 of 12 mice compared to 2 of 12 of the parental cell line. In the present study, the tumor-selective telomerase dependent OBP-401 adenovirus was injected intratumorally (i.t.) (1 × 108 PFU) when the high-metastatic MDA-MB-231 primary tumor expressing red fluorescent protein (MDA-MB-231-RFP) reached approximately 500 mm3 (diameter; 10 mm). The mock-infected orthotopic primary tumor grew rapidly. After i.t. OBP-401 injection, the growth of the orthotopic tumors was arrested. Six weeks after implantation, the fluorescent area and fluorescence intensity showed no increase from the beginning of treatment. OBP-401 was then injected into high-metastatic MDA-MB-231-RFP primary orthotopic tumor growing in mice which already had developed metastasis within lymphatic ducts. All 7 of 7 control mice subsequently developed lymph node metastasis. In contrast, none of 7 mice which received OBP-401 had lymph node metastasis. Seven of 7 control mice also had gross lung metastasis. In contrast, none of the 7 mice which received OBP-401 had gross lung metastasis. Confocal laser microscopy imaging demonstrated that all control mice had diffuse lung metastases. In contrast, all 7 mice which received OBP-401 only had a few metastatic cells in the lung. OBP-401 treatment significantly extended survival of the treated mice.
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- 2016
8. Fluorescence-guided surgery of a highly-metastatic variant of human triple-negative breast cancer targeted with a cancer-specific GFP adenovirus prevents recurrence
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Yano, Shuya, Takehara, Kiyoto, Miwa, Shinji, Kishimoto, Hiroyuki, Tazawa, Hiroshi, Urata, Yasuo, Kagawa, Shunsuke, Bouvet, Michael, Fujiwara, Toshiyoshi, and Hoffman, Robert M
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Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Cancer ,Breast Cancer ,Adenoviridae ,Animals ,Cell Line ,Tumor ,Cells ,Cultured ,Disease Models ,Animal ,Female ,Gene Expression ,Genetic Vectors ,Green Fluorescent Proteins ,Humans ,Mice ,Microscopy ,Fluorescence ,Optical Imaging ,Recurrence ,Surgery ,Computer-Assisted ,Transduction ,Genetic ,Triple Negative Breast Neoplasms ,Xenograft Model Antitumor Assays ,breast cancer ,triple negative ,nude mice ,orthotopic ,fluorescence-guided surgery ,telomerase dependent ,adenovirus ,GFP/RFP ,survival ,Oncology and carcinogenesis - Abstract
We have previously developed a genetically-engineered GFP-expressing telomerase-dependent adenovirus, OBP-401, which can selectively illuminate cancer cells. In the present report, we demonstrate that targeting a triple-negative high-invasive human breast cancer, orthotopically-growing in nude mice, with OBP-401 enables curative fluorescence-guided surgery (FGS). OBP-401 enabled complete resection and prevented local recurrence and greatly inhibited lymph-node metastasis due to the ability of the virus to selectively label and subsequently kill cancer cells. In contrast, residual breast cancer cells become more aggressive after bright (white)-light surgery (BLS). OBP-401-based FGS also improved the overall survival compared with conventional BLS. Thus, metastasis from a highly-aggressive triple-negative breast cancer can be prevented by FGS in a clinically-relevant mouse model.
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- 2016
9. Tumor-specific cell-cycle decoy by Salmonella typhimurium A1-R combined with tumor-selective cell-cycle trap by methioninase overcome tumor intrinsic chemoresistance as visualized by FUCCI imaging
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Yano, Shuya, Takehara, Kiyoto, Zhao, Ming, Tan, Yuying, Han, Qinghong, Li, Shukuan, Bouvet, Michael, Fujiwara, Toshiyoshi, and Hoffman, Robert M
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Cancer ,Digestive Diseases ,Animals ,Antineoplastic Agents ,Carbon-Sulfur Lyases ,Cell Cycle ,Cisplatin ,Drug Resistance ,Neoplasm ,Fluorescence ,G2 Phase ,HeLa Cells ,Humans ,Imaging ,Three-Dimensional ,Mice ,Nude ,Neoplasms ,Paclitaxel ,Recombinant Proteins ,S Phase ,Salmonella typhimurium ,Ubiquitination ,cancer ,cell-cycle ,cisplatinum ,decoy ,FUCCI ,methioninase ,nude mice ,paclitaxel ,Salmonella typhimurium A1-R ,stomach cancer ,trap ,Hela Cells ,Biochemistry and Cell Biology ,Developmental Biology - Abstract
We previously reported real-time monitoring of cell cycle dynamics of cancer cells throughout a live tumor intravitally using a fluorescence ubiquitination cell cycle indicator (FUCCI). Approximately 90% of cancer cells in the center and 80% of total cells of an established tumor are in G0/G1 phase. Longitudinal real-time FUCCI imaging demonstrated that cytotoxic agents killed only proliferating cancer cells at the surface and, in contrast, and had little effect on the quiescent cancer cells. Resistant quiescent cancer cells restarted cycling after the cessation of chemotherapy. Thus cytotoxic chemotherapy which targets cells in S/G2/M, is mostly ineffective on solid tumors, but causes toxic side effects on tissues with high fractions of cycling cells, such as hair follicles, bone marrow and the intestinal lining. We have termed this phenomenon tumor intrinsic chemoresistance (TIC). We previously demonstrated that tumor-targeting Salmonella typhimurium A1-R (S. typhimurium A1-R) decoyed quiescent cancer cells in tumors to cycle from G0/G1 to S/G2/M demonstrated by FUCCI imaging. We have also previously shown that when cancer cells were treated with recombinant methioninase (rMETase), the cancer cells were selectively trapped in S/G2, shown by cell sorting as well as by FUCCI. In the present study, we show that sequential treatment of FUCCI-expressing stomach cancer MKN45 in vivo with S. typhimurium A1-R to decoy quiescent cancer cells to cycle, with subsequent rMETase to selectively trap the decoyed cancer cells in S/G2 phase, followed by cisplatinum (CDDP) or paclitaxel (PTX) chemotherapy to kill the decoyed and trapped cancer cells completely prevented or regressed tumor growth. These results demonstrate the effectiveness of the praradigm of "decoy, trap and shoot" chemotherapy.
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- 2016
10. Adenoviral targeting of malignant melanoma for fluorescence-guided surgery prevents recurrence in orthotopic nude-mouse models
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Yano, Shuya, Takehara, Kiyoto, Kishimoto, Hiroyuki, Urata, Yasuo, Kagawa, Shunsuke, Bouvet, Michael, Fujiwara, Toshiyoshi, and Hoffman, Robert M
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Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Cancer ,Rare Diseases ,Adenoviridae ,Animals ,Cell Line ,Tumor ,Disease Models ,Animal ,Fluorescence ,Humans ,Melanoma ,Experimental ,Mice ,Mice ,Nude ,Neoplasm Recurrence ,Local ,Optical Imaging ,melanoma ,nude mice ,fluorescence-guided surgery ,adenovirus ,OBP-401 ,Oncology and carcinogenesis - Abstract
Malignant melanoma requires precise resection in order to avoid metastatic recurrence. We report here that the telomerase-dependent, green fluorescent protein (GFP)-containing adenovirus OBP-401 could label malignant melanoma with GFP in situ in orthotopic mouse models. OBP-401-based fluorescence-guided surgery (FGS) resulted in the complete resection of malignant melanoma in the orthotopic models, where conventional bright-light surgery (BLS) could not. High-dose administration of OBP-401 enabled FGS without residual cancer cells or recurrence, due to its dual effect of cancer-cell labeling with GFP and killing.
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- 2016
11. Improved Resection and Outcome of Colon-Cancer Liver Metastasis with Fluorescence-Guided Surgery Using In Situ GFP Labeling with a Telomerase-Dependent Adenovirus in an Orthotopic Mouse Model.
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Yano, Shuya, Takehara, Kiyoto, Miwa, Shinji, Kishimoto, Hiroyuki, Hiroshima, Yukihiko, Murakami, Takashi, Urata, Yasuo, Kagawa, Shunsuke, Bouvet, Michael, Fujiwara, Toshiyoshi, and Hoffman, Robert M
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Cell Line ,Tumor ,Animals ,Humans ,Mice ,Nude ,Adenoviridae ,Colonic Neoplasms ,Liver Neoplasms ,Neoplasm Metastasis ,Telomerase ,Green Fluorescent Proteins ,Cell Line ,Tumor ,Mice ,Nude ,General Science & Technology - Abstract
Fluorescence-guided surgery (FGS) of cancer is an area of intense development. In the present report, we demonstrate that the telomerase-dependent green fluorescent protein (GFP)-containing adenovirus OBP-401 could label colon-cancer liver metastasis in situ in an orthotopic mouse model enabling successful FGS. OBP-401-GFP-labeled liver metastasis resulted in complete resection with FGS, in contrast, conventional bright-light surgery (BLS) did not result in complete resection of the metastasis. OBP-401-FGS reduced the recurrence rate and prolonged over-all survival compared with BLS. In conclusion, adenovirus OBP-401 is a powerful tool to label liver metastasis in situ with GFP which enables its complete resection, not possible with conventional BLS.
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- 2016
12. Long-term survival without recurrence after surgery for gastric yolk sac tumor-like carcinoma: a case report
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Umeda, Hibiki, Kikuchi, Satoru, Kuroda, Shinji, Yano, Shuya, Tanaka, Takehiro, Noma, Kazuhiro, Nishizaki, Masahiko, Kagawa, Shunsuke, Umeda, Yuzo, and Fujiwara, Toshiyoshi
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- 2021
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13. Tumor-targeting Salmonella typhimurium A1-R inhibits human prostate cancer experimental bone metastasis in mouse models
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Toneri, Makoto, Miwa, Shinji, Zhang, Yong, Hu, Cameron, Yano, Shuya, Matsumoto, Yasunori, Bouvet, Michael, Nakanishi, Hayao, Hoffman, Robert M, and Zhao, Ming
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Prevention ,Prostate Cancer ,Aging ,Cancer ,Urologic Diseases ,Animals ,Biological Therapy ,Bone Density Conservation Agents ,Bone Neoplasms ,Combined Modality Therapy ,Diphosphonates ,Green Fluorescent Proteins ,Humans ,Imidazoles ,Male ,Mice ,Mice ,Nude ,Prostatic Neoplasms ,Salmonella Infections ,Animal ,Salmonella typhimurium ,Tumor Cells ,Cultured ,Xenograft Model Antitumor Assays ,Zoledronic Acid ,prostate cancer ,bone metastasis ,GFP/RFP ,zoledronic acid ,bacterial therapy ,Oncology and Carcinogenesis - Abstract
Bone metastasis is a frequent occurrence in prostate cancer patients and often is lethal. Zoledronic acid (ZOL) is often used for bone metastasis with limited efficacy. More effective models and treatment methods are required to improve the outcome of prostate cancer patients. In the present study, the effects of tumor-targeting Salmonella typhimurium A1-R were analyzed in vitro and in vivo on prostate cancer cells and experimental bone metastasis. Both ZOL and S. typhimurium A1-R inhibited the growth of PC-3 cells expressing red fluorescent protien in vitro. To investigate the efficacy of S. typhimurium A1-R on prostate cancer experimental bone metastasis, we established models of both early and advanced stage bone metastasis. The mice were treated with ZOL, S. typhimurium A1-R, and combination therapy of both ZOL and S. typhimurium A1-R. ZOL and S. typhimurium A1-R inhibited the growth of solitary bone metastases. S. typhimurium A1-R treatment significantly decreased bone metastasis and delayed the appearance of PC-3 bone metastases of multiple mouse models. Additionally, S. typhimurium A1-R treatment significantly improved the overall survival of the mice with multiple bone metastases. The results of the present study indicate that S. typhimurium A1-R is useful to prevent and inhibit prostate cancer bone metastasis and has potential for future clinical use in the adjuvant setting.
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- 2015
14. Precise navigation surgery of tumours in the lung in mouse models enabled by in situ fluorescence labelling with a killer-reporter adenovirus
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Yano, Shuya, Zhang, Yong, Miwa, Shinji, Kishimoto, Hiroyuki, Urata, Yasuo, Bouvet, Michael, Kagawa, Shunsuke, Fujiwara, Toshiyoshi, and Hoffman, Robert M
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Cancer ,Lung Cancer ,Lung ,Imaging/CT MRI etc ,Non-Small Cell Lung Cancer ,Thoracic Surgery - Abstract
BackgroundCurrent methods of image-guided surgery of tumours of the lung mostly rely on CT. A sensitive procedure of selective tumour fluorescence labelling would allow simple and high-resolution visualisation of the tumour for precise surgical navigation.MethodsHuman lung cancer cell lines H460 and A549 were genetically transformed to express red fluorescent protein (RFP). Tumours were grown subcutaneously for each cell line and harvested and minced for surgical orthotopic implantation on the left lung of nude mice. Tumour growth was measured by fluorescence imaging. After the tumours reached 5 mm in diameter, they were injected under fluorescence guidance with the telomerase-dependent green fluorescent protein (GFP)-containing adenovirus, OBP-401. Viral labelling of the lung tumours with GFP precisely colocalised with tumour RFP expression. Three days after administration of OBP-401, fluorescence-guided surgery (FGS) was performed.ResultsFGS of tumours in the lung was enabled by labelling with a telomerase-dependent adenovirus containing the GFP gene. Tumours in the lung were selectively and brightly labelled. FGS enabled complete lung tumour resection with no residual fluorescent tumour.ConclusionsFGS of tumours in the lung is feasible and more effective than bright-light surgery.
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- 2015
15. Experimental Curative Fluorescence-guided Surgery of Highly Invasive Glioblastoma Multiforme Selectively Labeled With a Killer-reporter Adenovirus
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Yano, Shuya, Miwa, Shinji, Kishimoto, Hiroyuki, Toneri, Makoto, Hiroshima, Yukihiko, Yamamoto, Mako, Bouvet, Michael, Urata, Yasuo, Tazawa, Hiroshi, Kagawa, Shunsuke, Fujiwara, Toshiyoshi, and Hoffman, Robert M
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Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Rare Diseases ,Brain Cancer ,Brain Disorders ,Cancer ,Neurosciences ,Adenoviridae ,Animals ,Cell Line ,Tumor ,Disease Models ,Animal ,Disease-Free Survival ,Fluorescence ,Glioblastoma ,Green Fluorescent Proteins ,Humans ,Mice ,Mice ,Nude ,Neoplasm Recurrence ,Local ,Optical Imaging ,Biological Sciences ,Technology ,Medical and Health Sciences ,Biotechnology ,Genetics ,Clinical sciences ,Medical biotechnology - Abstract
Fluorescence-guided surgery (FGS) of cancer is an area of intense current interest. However, although benefits have been demonstrated with FGS, curative strategies need to be developed. Glioblastoma multiforme (GBM) is one of the most invasive of cancers and is not totally resectable using standard bright-light surgery (BLS) or current FGS strategies. We report here a curative strategy for FGS of GBM. In this study, telomerase-dependent adenovirus OBP-401 infection brightly and selectively labeled GBM with green fluorescent protein (GFP) for FGS in orthotopic nude mouse models. OBP-401-based FGS enabled curative resection of GBM without recurrence for at least 150 days, compared to less than 30 days with BLS.
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- 2015
16. Targeting tumors with a killer-reporter adenovirus for curative fluorescence-guided surgery of soft-tissue sarcoma
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Yano, Shuya, Miwa, Shinji, Kishimoto, Hiroyuki, Uehara, Fuminari, Tazawa, Hiroshi, Toneri, Makoto, Hiroshima, Yukihiko, Yamamoto, Mako, Urata, Yasuo, Kagawa, Shunsuke, Bouvet, Michael, Fujiwara, Toshiyoshi, and Hoffman, Robert M
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Cancer ,Rare Diseases ,Adenoviridae ,Animals ,Cell Line ,Tumor ,Cells ,Cultured ,Fluorescence ,Genetic Vectors ,Green Fluorescent Proteins ,Luminescent Agents ,Luminescent Proteins ,Mice ,Mice ,Nude ,Optical Imaging ,Sarcoma ,Experimental ,Soft Tissue Neoplasms ,Surgery ,Computer-Assisted ,soft tissue sarcoma ,nude mice ,fluorescence-guided surgery ,adenovirus ,OBP-401 ,Oncology and Carcinogenesis - Abstract
Fluorescence-guided surgery (FGS) of cancer is an area of intense interest. However, FGS of cancer has not yet been shown to be curative due to residual microscopic disease. Human fibrosarcoma HT1080 expressing red fluorescent protein (RFP) was implanted orthotopically in the quadriceps femoris muscle of nude mice. The tumor-bearing mice were injected with high and low-dose telomerase-dependent, green fluorescent protein (GFP)-containing adenovirus OBP-401, which labeled the tumor with GFP. Fluorescence-guided surgery (FGS) or bright light surgery (BLS) was then performed. OBP-401 could label soft-tissue sarcoma (STS) with GFP in situ, concordant with RFP. OBP-401-based FGS resulted in superior resection of STS in the orthotopic model of soft-tissue sarcoma, compared to BLS. High-dose administration of OBP-401 enabled FGS without residual sarcoma cells or local or metastatic recurrence, due to its dual effect of cancer-cell labeling with GFP and killing. High-dose OBP-401 based-FGS improved disease free survival (p = 0.00049) as well as preserved muscle function compared with BLS. High-dose OBP-401-based FGS could cure STS, a presently incurable disease. Since the parent virus of OBP-401, OBP-301, has been previously proven safe in a Phase I clinical trial, it is expected the OBP-401-FGS technology described in the present report should be translatable to the clinic in the near future.
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- 2015
17. Intraperitoneal administration of tumor-targeting Salmonella typhimurium A1-R inhibits disseminated human ovarian cancer and extends survival in nude mice
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Matsumoto, Yasunori, Miwa, Shinji, Zhang, Yong, Zhao, Ming, Yano, Shuya, Uehara, Fuminari, Yamamoto, Mako, Hiroshima, Yukihiko, Toneri, Makoto, Bouvet, Michael, Matsubara, Hisahiro, Tsuchiya, Hiroyuki, and Hoffman, Robert M
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Cancer ,Rare Diseases ,Digestive Diseases ,Prevention ,Emerging Infectious Diseases ,Ovarian Cancer ,Orphan Drug ,Animals ,Bacterial Load ,Biological Therapy ,Cell Line ,Tumor ,Female ,Humans ,Injections ,Intraperitoneal ,Injections ,Intravenous ,Mice ,Nude ,Ovarian Neoplasms ,Peritoneal Neoplasms ,Salmonella typhimurium ,Time Factors ,Virulence ,Xenograft Model Antitumor Assays ,ovarian cancer ,orthotopic ,mouse model ,bacterial therapy ,Salmonella typhimurium A1-R ,Oncology and Carcinogenesis - Abstract
UnlabelledPeritoneal disseminated cancer is highly treatment resistant. We here report the efficacy of intraperitoneal (i.p.) administration of tumor-targeting Salmonella typhimurium A1-R in a nude mouse model of disseminated human ovarian cancer. The mouse model was established by intraperitoneal injection of the human ovarian cancer cell line SKOV3-GFP. Seven days after implantation, mice were treated with S. typhimurium A1-R via intravenous (i.v.) or i.p. administration at the same dose, 5 × 10(7) CFU, once per week. Both i.v. and i.p. treatments effected prolonged survival compared with the untreated control group (P=0.025 and P
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- 2015
18. Cancer cells mimic in vivo spatial-temporal cell-cycle phase distribution and chemosensitivity in 3-dimensional Gelfoam® histoculture but not 2-dimensional culture as visualized with real-time FUCCI imaging
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Yano, Shuya, Miwa, Shinji, Mii, Sumiyuki, Hiroshima, Yukihiko, Uehara, Fuminaru, Kishimoto, Hiroyuki, Tazawa, Hiroshi, Zhao, Ming, Bouvet, Michael, Fujiwara, Toshiyoshi, and Hoffman, Robert M
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Biochemistry and Cell Biology ,Biological Sciences ,Cancer ,Bioengineering ,Animals ,Cell Culture Techniques ,Cell Cycle ,Cell Death ,Cell Line ,Tumor ,Cisplatin ,Computer Systems ,Female ,Fluorescence ,Gelatin Sponge ,Absorbable ,Humans ,Mice ,Nude ,Molecular Imaging ,Neoplasms ,Paclitaxel ,Time Factors ,Ubiquitination ,cell cycle ,chemotherapy ,FUCCI ,Gelfoam ,GFP ,imaging ,RFP ,stomach cancer ,Three dimensional-histoculture culture ,Gelfoam® ,Developmental Biology ,Biochemistry and cell biology - Abstract
The phase of the cell cycle can determine whether a cancer cell can respond to a given drug. We previously reported monitoring of real-time cell cycle dynamics of cancer cells throughout a live tumor, intravitally in live mice, using a fluorescence ubiquitination-based cell-cycle indicator (FUCCI). Approximately 90% of cancer cells in the center and 80% of total cells of an established tumor are in G0/G1 phase. Longitudinal real-time imaging demonstrated that cytotoxic agents killed only proliferating cancer cells at the surface and, in contrast, had little effect on quiescent cancer cells, which are the vast majority of an established tumor. Moreover, resistant quiescent cancer cells restarted cycling after cessation of chemotherapy. These results suggested why most drugs currently in clinical use, which target cancer cells in S/G2/M, are mostly ineffective on solid tumors. In the present report, we used FUCCI imaging and Gelfoam® collagen-sponge-gel histoculture, to demonstrate in real time, that the cell-cycle phase distribution of cancer cells in Gelfoam® and in vivo tumors is highly similar, whereby only the surface cells proliferate and interior cells are quiescent in G0/G1. This is in contrast to 2D culture where most cancer cells cycle. Similarly, the cancer cells responded similarly to toxic chemotherapy in Gelfoam® culture as in vivo, and very differently than cancer cells in 2D culture which were much more chemosensitive. Gelfoam® culture of FUCCI-expressing cancer cells offers the opportunity to image the cell cycle of cancer cells continuously and to screen for novel effective therapies to target quiescent cells, which are the majority in a tumor and which would have a strong probability to be effective in vivo.
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- 2015
19. Traditional Chinese medicine herbal mixture LQ arrests FUCCI-expressing HeLa cells in G0/G1 phase in 2D plastic, 2.5D Matrigel®, and 3D Gelfoam® culture visualized with FUCCI imaging
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Zhang, Lei, Wu, Chengyu, Bouvet, Michael, Yano, Shuya, and Hoffman, Robert M
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Cancer ,Animals ,Antineoplastic Agents ,Phytogenic ,Cell Cycle ,Cell Movement ,Cell Proliferation ,Collagen ,Drug Combinations ,Drug Synergism ,Fluorescence ,Fluorescent Antibody Technique ,G1 Phase ,Gelatin Sponge ,Absorbable ,HeLa Cells ,Humans ,Image Processing ,Computer-Assisted ,Laminin ,Medicine ,Chinese Traditional ,Mice ,Microscopy ,Confocal ,Paclitaxel ,Plant Extracts ,Plastics ,Proteoglycans ,Resting Phase ,Cell Cycle ,Ubiquitination ,TCM ,herbal mixture ,LQ ,paclitaxel ,FUCCI ,Hela Cells ,Oncology and Carcinogenesis - Abstract
We used the fluorescence ubiquitination-based cell cycle indicator (FUCCI) to monitor cell cycle arrest after treatment of FUCCI-expressing HeLa cells (FUCCI-HeLa) with a traditional Chinese medicine (TCM) herbal mixture LQ, previously shown to have anti-tumor and anti-metastatic activity in mouse models. Paclitaxel was used as the positive control. In 2D monolayer culture, the untreated control had approximately 45% of the cells in S/G₂/M phase. In contrast, the LQ-treated cells (9 mg/ml) were mostly in the G₀/G₁ (>90%) after 72 hours. After treatment with paclitaxel (0.01 μm), for 72 hours, 95% of the cells were in S/G₂/M. In 2.5D Matrigel culture, the colonies in the untreated control group had 40% of the cells in S/G₂/M. LQ arrested the cells in G₀/G₁ after 72 hours. Paclitaxel arrested almost all the cells in S/G₂/M after 72 hours. In 3D Gelfoam culture, the untreated control culture had approximately 45% of cells in G₂/M. In contrast, the LQ-treated cells were mostly in G₀/G₁ phase (>80%) after 72 hours treatment. Paclitaxel resulted in 90% of the cells arrested in S/G₂/M after 72 hours. The present report suggests the non-toxic LQ has potential to maintain cancers in a quiescent state for long periods of time.
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- 2015
20. Cell-cycle fate-monitoring distinguishes individual chemosensitive and chemoresistant cancer cells in drug-treated heterogeneous populations demonstrated by real-time FUCCI imaging
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Miwa, Shinji, Yano, Shuya, Kimura, Hiroaki, Yamamoto, Mako, Toneri, Makoto, Matsumoto, Yasunori, Uehara, Fuminari, Hiroshima, Yukihiko, Murakami, Takashi, Hayashi, Katsuhiro, Yamamoto, Norio, Bouvet, Michael, Fujiwara, Toshiyoshi, Tsuchiya, Hiroyuki, and Hoffman, Robert M
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Biochemistry and Cell Biology ,Biological Sciences ,Cancer ,Antineoplastic Agents ,Apoptosis ,Cell Cycle ,Cell Lineage ,Cisplatin ,Doxorubicin ,HeLa Cells ,Humans ,Mitosis ,Neoplasms ,Optical Imaging ,Proportional Hazards Models ,Time-Lapse Imaging ,cancer ,cell cycle ,chemoresistance ,chemosensitivity ,cisplatinum ,doxorubicin ,FUCCI ,GFP ,RFP ,HeLa ,time-lapse imaging ,tumor heterogeneity ,Hela Cells ,Developmental Biology ,Biochemistry and cell biology - Abstract
Essentially every population of cancer cells within a tumor is heterogeneous, especially with regard to chemosensitivity and resistance. In the present study, we utilized the fluorescence ubiquitination-based cell cycle indicator (FUCCI) imaging system to investigate the correlation between cell-cycle behavior and apoptosis after treatment of cancer cells with chemotherapeutic drugs. HeLa cells expressing FUCCI were treated with doxorubicin (DOX) (5 μM) or cisplatinum (CDDP) (5 μM) for 3 h. Cell-cycle progression and apoptosis were monitored by time-lapse FUCCI imaging for 72 h. Time-lapse FUCCI imaging demonstrated that both DOX and CDDP could induce cell cycle arrest in S/G2/M in almost all the cells, but a subpopulation of the cells could escape the block and undergo mitosis. The subpopulation which went through mitosis subsequently underwent apoptosis, while the cells arrested in S/G2/M survived. The present results demonstrate that chemoresistant cells can be readily identified in a heterogeneous population of cancer cells by S/G2/M arrest, which can serve in future studies as a visible target for novel agents that kill cell-cycle-arrested cells.
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- 2015
21. Tumor-Targeting Salmonella typhimurium A1-R Arrests a Chemo-Resistant Patient Soft-Tissue Sarcoma in Nude Mice.
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Hiroshima, Yukihiko, Zhao, Ming, Zhang, Yong, Zhang, Nan, Maawy, Ali, Murakami, Takashi, Mii, Sumiyuki, Uehara, Fuminari, Yamamoto, Mako, Miwa, Shinji, Yano, Shuya, Momiyama, Masashi, Mori, Ryutaro, Matsuyama, Ryusei, Chishima, Takashi, Tanaka, Kuniya, Ichikawa, Yasushi, Bouvet, Michael, Endo, Itaru, and Hoffman, Robert M
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Animals ,Mice ,Mice ,Nude ,Salmonella typhimurium ,Salmonella Infections ,Sarcoma ,Soft Tissue Neoplasms ,Disease Models ,Animal ,Sulfonamides ,Pyrimidines ,Deoxycytidine ,Antineoplastic Agents ,Xenograft Model Antitumor Assays ,Disease Models ,Animal ,Nude ,General Science & Technology - Abstract
A patient-derived nude-mouse model of soft-tissue sarcoma has been established and treated in the following groups: (1) untreated controls; (2) gemcitabine (GEM) (80 mg/kg, ip, weekly, 3 weeks); (3) Pazopanib (100 mg/kg, orally, daily, 3 weeks) and (4) Salmonella typhimurium A1-R (5 × 10(7) CFU/body, ip, weekly, 3 weeks). The sarcoma was resistant to GEM (p = 0.879). Pazopanib tended to reduce the tumor volume compared to the untreated mice, but there was no significant difference (p = 0.115). S. typhimurium A1-R significantly inhibited tumor growth compared to the untreated mice (p = 0.001). S. typhimurium A1-R was the only effective treatment for the soft-tissue sarcoma nude mouse model among all treatments including a newly approved multiple tyrosine kinase inhibitor; Pazopanib. These results suggest tumor-targeting S. typhimurium A1-R is a promising treatment for chemo-resistant soft-tissue sarcoma.
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- 2015
22. Establishment of a patient-derived orthotopic Xenograft (PDOX) model of HER-2-positive cervical cancer expressing the clinical metastatic pattern.
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Hiroshima, Yukihiko, Zhang, Yong, Zhang, Nan, Maawy, Ali, Mii, Sumiyuki, Yamamoto, Mako, Uehara, Fuminari, Miwa, Shinji, Yano, Shuya, Murakami, Takashi, Momiyama, Masashi, Chishima, Takashi, Tanaka, Kuniya, Ichikawa, Yasushi, Bouvet, Michael, Murata, Takuya, Endo, Itaru, and Hoffman, Robert M
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Animals ,Humans ,Mice ,Mice ,Nude ,Cell Transformation ,Neoplastic ,Neoplasm Metastasis ,Disease Models ,Animal ,Receptor ,erbB-2 ,Uterine Cervical Neoplasms ,Female ,Receptor ,ErbB-2 ,Cell Transformation ,Neoplastic ,Disease Models ,Animal ,Nude ,Receptor ,ErbB-2 ,General Science & Technology - Abstract
Squamous cell carcinoma of the cervix, highly prevalent in the developing world, is often metastatic and treatment resistant with no standard treatment protocol. Our laboratory pioneered the patient-derived orthotopic xenograft (PDOX) nude mouse model with the technique of surgical orthotopic implantation (SOI). Unlike subcutaneous transplant patient-derived xenograft (PDX) models, PDOX models metastasize. Most importantly, the metastasis pattern correlates to the patient. In the present report, we describe the development of a PDOX model of HER-2-positive cervical cancer. Metastasis after SOI in nude mice included peritoneal dissemination, liver metastasis, lung metastasis as well as lymph node metastasis reflecting the metastatic pattern in the donor patient. Metastasis was detected in 4 of 6 nude mice with primary tumors. Primary tumors and metastases in the nude mice had histological structures similar to the original tumor and were stained by an anti-HER-2 antibody in the same pattern as the patient's cancer. The metastatic pattern, histology and HER-2 tumor expression of the patient were thus preserved in the PDOX model. In contrast, subcutaneous transplantation of the patient's cervical tumors resulted in primary growth but not metastasis.
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- 2015
23. Tumor-Targeting Salmonella typhimurium A1-R in Combination with Trastuzumab Eradicates HER-2-Positive Cervical Cancer Cells in Patient-Derived Mouse Models.
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Hiroshima, Yukihiko, Zhang, Yong, Zhao, Ming, Zhang, Nan, Murakami, Takashi, Maawy, Ali, Mii, Sumiyuki, Uehara, Fuminari, Yamamoto, Mako, Miwa, Shinji, Yano, Shuya, Momiyama, Masashi, Mori, Ryutaro, Matsuyama, Ryusei, Chishima, Takashi, Tanaka, Kuniya, Ichikawa, Yasushi, Bouvet, Michael, Endo, Itaru, and Hoffman, Robert M
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Animals ,Humans ,Mice ,Mice ,Nude ,Salmonella typhimurium ,Disease Models ,Animal ,Receptor ,erbB-2 ,Transplantation ,Heterologous ,Immunohistochemistry ,Uterine Cervical Neoplasms ,Female ,Trastuzumab ,Receptor ,ErbB-2 ,Disease Models ,Animal ,Nude ,Receptor ,ErbB-2 ,Transplantation ,Heterologous ,General Science & Technology - Abstract
We have previously developed mouse models of HER-2-positive cervical cancer. Tumors in nude mice had histological structures similar to the original tumor and were stained by anti-HER-2 antibody in the same pattern as the patient's cancer. We have also previously developed tumor-targeting Salmonella typhimurium A1-R and have demonstrated its efficacy against patient-derived tumor mouse models, both alone and in combination. In the current study, we determined the efficacy of S. typhimurium A1-R in combination with trastuzumab on a patient-cancer nude-mouse model of HER-2 positive cervical cancer. Mice were randomized to 5 groups and treated as follows: (1) no treatment; (2) carboplatinum (30 mg/kg, ip, weekly, 5 weeks); (3) trastuzumab (20 mg/kg, ip, weekly, 5 weeks); (4) S. typhimurium A1-R (5 × 107 CFU/body, ip, weekly, 5 weeks); (5) S. typhimurium A1-R (5 × 107 CFU/body, ip, weekly, 5 weeks) + trastuzumab (20 mg/kg, ip, weekly, 5 weeks). All regimens had significant efficacy compared to the untreated mice. The relative tumor volume of S. typhimurium A1-R + trastuzumab-treated mice was smaller compared to trastuzumab alone (p = 0.007) and S. typhimurium A1-R alone (p = 0.039). No significant body weight loss was found compared to the no treatment group except for carboplatinum-treated mice (p = 0.021). Upon histological examination, viable tumor cells were not detected, and replaced by stromal cells in the tumors treated with S. typhimurium A1-R + trastuzumab. The results of the present study suggest that S. typhimurium A1-R and trastuzumab in combination are highly effective against HER-2-expressing cervical cancer.
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- 2015
24. Fluorescence-guided surgery of retroperitoneal-implanted human fibrosarcoma in nude mice delays or eliminates tumor recurrence and increases survival compared to bright-light surgery.
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Uehara, Fuminari, Hiroshima, Yukihiko, Miwa, Shinji, Tome, Yasunori, Yano, Shuya, Yamamoto, Mako, Matsumoto, Yasunori, Maehara, Hiroki, Tanaka, Kazuhiro, Bouvet, Michael, Kanaya, Fuminori, and Hoffman, Robert M
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Cell Line ,Tumor ,Animals ,Humans ,Mice ,Mice ,Nude ,Fibrosarcoma ,Retroperitoneal Neoplasms ,Neoplasm Recurrence ,Local ,Green Fluorescent Proteins ,Surgery ,Computer-Assisted ,Fluorescence ,Female ,Optical Imaging ,Cell Line ,Tumor ,Nude ,Neoplasm Recurrence ,Local ,Surgery ,Computer-Assisted ,General Science & Technology - Abstract
The aim of this study is to determine if fluorescence-guided surgery (FGS) can eradicate human fibrosarcoma growing in the retroperitoneum of nude mice. One week after retroperitoneal implantation of human HT1080 fibrosarcoma cells, expressing green fluorescent protein (GFP) (HT-1080-GFP), in nude mice, bright-light surgery (BLS) was performed on all tumor-bearing mice (n = 22). After BLS, mice were randomized into 2 treatment groups; BLS-only (n = 11) or the combination of BLS + FGS (n = 11). The residual tumors remaining after BLS were resected with FGS using a hand-held portable imaging system under fluorescence navigation. The average residual tumor area after BLS + FGS was significantly smaller than after BLS-only (0.4 ± 0.4 mm(2) and 10.5 ± 2.4 mm(2), respectively; p = 0.006). Five weeks after surgery, the fluorescent-tumor areas of BLS- and BLS + FGS-treated mice were 379 ± 147 mm(2) and 11.7 ± 6.9 mm(2), respectively, indicating that FGS greatly inhibited tumor recurrence compared to BLS. The combination of BLS + FGS significantly decreased fibrosarcoma recurrence compared to BLS-only treated mice (p < 0.001). Mice treated with BLS+FGS had a significantly higher disease-free survival rate than mice treated with BLS-only at five weeks after surgery. These results suggest that combination of BLS + FGS significantly reduced the residual fibrosarcoma volume after BLS and improved disease-free survival.
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- 2015
25. Inhibition of spontaneous and experimental lung metastasis of soft-tissue sarcoma by tumor-targeting Salmonella typhimurium A1-R
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Miwa, Shinji, Zhang, Yong, Baek, Kyung-Eun, Uehara, Fuminari, Yano, Shuya, Yamamoto, Mako, Hiroshima, Yukihiko, Matsumoto, Yasunori, Kimura, Hiroaki, Hayashi, Katsuhiro, Yamamoto, Norio, Bouvet, Michael, Tsuchiya, Hiroyuki, Hoffman, Robert M, and Zhao, Ming
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Cancer ,Lung ,Lung Cancer ,Emerging Infectious Diseases ,Orphan Drug ,Rare Diseases ,Animals ,Cell Line ,Tumor ,Disease Models ,Animal ,Female ,Fibrosarcoma ,Humans ,Lung Neoplasms ,Mice ,Mice ,Nude ,Neoplasm Metastasis ,Prognosis ,Salmonella typhimurium ,Sarcoma ,Xenograft Model Antitumor Assays ,HT-1080 ,orthotopic model ,nude mice ,lung metastasis ,bacterial therapy ,Oncology and Carcinogenesis - Abstract
Prognosis of patients with lung metastases of soft-tissue sarcoma is still poor. Therefore, novel systemic therapy is needed to improve the survival of soft-tissue sarcoma. In the present study, tumor-targeting therapy with a genetically-modified auxotrophic strain of Salmonella typhimurium, termed A1-R, was evaluated. Mouse models of primary soft tissue sarcoma and spontaneous lung metastasis were obtained by orthotopic intra-muscular injection of HT1080-RFP human fibrosarcoma cells. S. typhimurium A1-R was administered from day 14, once a week for two weeks. On day 28, lung samples were excised and observed with a fluorescence imaging system. The number of lung metastasis was 8.8 ± 3.4 in the untreated group and 0.8 ± 0.8 in the treated group (P = 0.024). A mouse model of experimental lung metastasis was obtained by tail vein injection of HT1080-RFP cells. The mice were treated with S. typhimurium A1-R (i.v.) on day 7, once a week for three weeks. S. typhimurium A1-R significantly reduced lung metastases and improved overall survival (P = 0.004). S. typhimurium A1-R bacterial therapy has future potential for treating advanced soft tissue sarcoma and improving prognosis of patients with lung metastasis.
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- 2014
26. Tumor-targeting Salmonella typhimurium A1-R decoys quiescent cancer cells to cycle as visualized by FUCCI imaging and become sensitive to chemotherapy
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Yano, Shuya, Zhang, Yong, Zhao, Ming, Hiroshima, Yukihiko, Miwa, Shinji, Uehara, Fuminari, Kishimoto, Hiroyuki, Tazawa, Hiroshi, Bouvet, Michael, Fujiwara, Toshiyoshi, and Hoffman, Robert M
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Cancer ,Animals ,Antineoplastic Agents ,Cell Line ,Tumor ,Humans ,Interphase ,Mice ,Mice ,Nude ,Salmonella typhimurium ,Stomach Neoplasms ,Time-Lapse Imaging ,Xenograft Model Antitumor Assays ,cell cycle ,chemotherapy ,decoy ,FUCCI ,GFP ,RFP ,imaging ,S ,typhimurium A1-R ,tumor-targeting bacteria ,fluorescence ubiquitination-based cell cycle indicator ,typhimurium ,GFP ,RFP ,imaging ,S. typhimurium A1-R ,fluorescence ubiquitination-based cell cycle indicator ,S. typhimurium ,Biochemistry and Cell Biology ,Developmental Biology - Abstract
Quiescent cancer cells are resistant to cytotoxic agents which target only proliferating cancer cells. Time-lapse imaging demonstrated that tumor-targeting Salmonella typhimurium A1-R (A1-R) decoyed cancer cells in monolayer culture and in tumor spheres to cycle from G0/G1 to S/G2/M, as demonstrated by fluorescence ubiquitination-based cell cycle indicator (FUCCI) imaging. A1-R infection of FUCCI-expressing subcutaneous tumors growing in nude mice also decoyed quiescent cancer cells, which were the majority of the cells in the tumors, to cycle from G0/G1 to S/G2/M, thereby making them sensitive to cytotoxic agents. The combination of A1-R and cisplatinum or paclitaxel reduced tumor size compared with A1-R monotherapy or cisplatinum or paclitaxel alone. The results of this study demonstrate that A1-R can decoy quiescent cancer cells to cycle to S/G2/M and sensitize them to cytotoxic chemotherapy. These results suggest a new paradigm of bacterial-decoy chemotherapy of cancer.
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- 2014
27. Efficacy of tumor-targeting Salmonella typhimurium A1-R in combination with anti-angiogenesis therapy on a pancreatic cancer patient-derived orthotopic xenograft (PDOX) and cell line mouse models
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Hiroshima, Yukihiko, Zhang, Yong, Murakami, Takashi, Maawy, Ali, Miwa, Shinji, Yamamoto, Mako, Yano, Shuya, Sato, Sho, Momiyama, Masashi, Mori, Ryutaro, Matsuyama, Ryusei, Chishima, Takashi, Tanaka, Kuniya, Ichikawa, Yasushi, Bouvet, Michael, Endo, Itaru, Zhao, Ming, and Hoffman, Robert M
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Pancreatic Cancer ,Rare Diseases ,Cancer ,Digestive Diseases ,Orphan Drug ,Development of treatments and therapeutic interventions ,5.2 Cellular and gene therapies ,5.1 Pharmaceuticals ,Angiogenesis Inhibitors ,Animals ,Cell Line ,Tumor ,Humans ,Male ,Mice ,Mice ,Nude ,Microscopy ,Confocal ,Pancreatic Neoplasms ,Real-Time Polymerase Chain Reaction ,Salmonella Infections ,Salmonella typhimurium ,Vascular Endothelial Growth Factor A ,Xenograft Model Antitumor Assays ,Pancreatic cancer ,Salmonella typhimurium A1-R ,patient-derived orthotopic xenograft ,orthotopic ,nude mice ,GFP ,VEGF ,anti-angiogenic therapy ,bevacizumab ,gemcitabine ,Oncology and Carcinogenesis - Abstract
The aim of the present study was to examine the efficacy of tumor-targeting Salmonella typhimurium A1-R treatment following anti-vascular endothelial growth factor (VEGF) therapy on VEGF-positive human pancreatic cancer. A pancreatic cancer patient-derived orthotopic xenograft (PDOX) that was VEGF-positive and an orthotopic VEGF-positive human pancreatic cancer cell line (MiaPaCa-2-GFP) as well as a VEGF-negative cell line (Panc-1) were tested. Nude mice with these tumors were treated with gemcitabine (GEM), bevacizumab (BEV), and S. typhimurium A1-R. BEV/GEM followed by S. typhimurium A1-R significantly reduced tumor weight compared to BEV/GEM treatment alone in the PDOX and MiaPaCa-2 models. Neither treatment was as effective in the VEGF-negative model as in the VEGF-positive models. These results demonstrate that S. typhimurium A1-R following anti-angiogenic therapy is effective on pancreatic cancer including the PDOX model, suggesting its clinical potential.
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- 2014
28. Fluorescence‐guided surgery improves outcome in an orthotopic osteosarcoma nude‐mouse model
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Miwa, Shinji, Hiroshima, Yukihiko, Yano, Shuya, Zhang, Yong, Matsumoto, Yasunori, Uehara, Fuminari, Yamamoto, Mako, Kimura, Hiroaki, Hayashi, Katsuhiro, Bouvet, Michael, Tsuchiya, Hiroyuki, and Hoffman, Robert M
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Rare Diseases ,Cancer ,Animals ,Bone Neoplasms ,Cisplatin ,Disease Models ,Animal ,Female ,Fluorescence ,Lung Neoplasms ,Mice ,Nude ,Osteosarcoma ,Treatment Outcome ,osteosarcoma ,RFP ,fluorescence-guided surgery ,orthotopic mouse model ,chemotherapy ,cisplatinum ,Biomedical Engineering ,Clinical Sciences ,Human Movement and Sports Sciences ,Orthopedics - Abstract
In order to develop a model for fluorescence-guided surgery (FGS), 143B human osteosarcoma cells expressing red fluorescent protein (RFP) were injected into the intramedullary cavity of the tibia in nude mice. The fluorescent areas of residual tumors after bright-light surgery (BLS) and FGS were 10.2 ± 2.4 mm(2) and 0.1 ± 0.1 mm(2) , respectively (p
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- 2014
29. Selective methioninase-induced trap of cancer cells in S/G 2 phase visualized by FUCCI imaging confers chemosensitivity
- Author
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Yano, Shuya, Li, Shukuan, Han, Qinghong, Tan, Yuying, Bouvet, Michael, Fujiwara, Toshiyoshi, and Hoffman, Robert M
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Cancer ,Antimetabolites ,Antineoplastic ,Antineoplastic Combined Chemotherapy Protocols ,Breast Neoplasms ,Carbon-Sulfur Lyases ,Drug Resistance ,Neoplasm ,Female ,Genes ,Reporter ,HeLa Cells ,Humans ,MCF-7 Cells ,Microscopy ,Confocal ,Microscopy ,Fluorescence ,Recombinant Proteins ,S Phase Cell Cycle Checkpoints ,Time Factors ,Transfection ,Uterine Cervical Neoplasms ,cell cycle ,FUCCI ,imaging ,S/G(2) phase block ,recombinant methioninase ,rMETase ,chemotherapy ,HeLa cells ,MCF-7 cells ,Hela Cells ,Oncology and Carcinogenesis - Abstract
A major impediment to the response of tumors to chemotherapy is that the large majority of cancer cells within a tumor are quiescent in G0/G1, where cancer cells are resistant to chemotherapy. To attempt to solve this problem of quiescent cells in a tumor, cancer cells were treated with recombinant methioninase (rMETase), which selectively traps cancer cells in S/G2. The cell cycle phase of the cancer cells was visualized with the fluorescence ubiquitination-based cell cycle indicator cell cycle indicator (FUCCI). At the time of rMETase-induced S/G2-phase blockage, identified by the cancer cells' green fluorescence by FUCCI imaging, the cancer cells were administered S/G2-dependent chemotherapy drugs, which interact with DNA or block DNA synthesis such as doxorubicin, cisplatin, or 5-fluorouracil. Treatment of cancer cells with drugs only, without rMETase-induced S/G2 phase blockage, led to the majority of the cancer-cell population being blocked in G0/G1 phase, identified by the cancer cells becoming red fluorescent in the FUCCI system. The G0/G1 blocked cells were resistant to the chemotherapy. In contrast, trapping of cancer cells in S/G2 phase by rMETase treatment followed by FUCCI-imaging-guided chemotherapy was highly effective in killing the cancer cells.
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- 2014
30. Osteosarcoma Cells Enhance Angiogenesis Visualized by Color‐Coded Imaging in the In Vivo Gelfoam® Assay
- Author
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Uehara, Fuminari, Tome, Yasunori, Miwa, Shinji, Hiroshima, Yukihiko, Yano, Shuya, Yamamoto, Mako, Mii, Sumiyuki, Maehara, Hiroki, Bouvet, Michael, Kanaya, Fuminori, and Hoffman, Robert M
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Biochemistry and Cell Biology ,Biological Sciences ,Transplantation ,Animals ,Cell Line ,Tumor ,Female ,Gelatin Sponge ,Absorbable ,Green Fluorescent Proteins ,Humans ,Implants ,Experimental ,Luminescent Proteins ,Mice ,Mice ,Nude ,Mice ,Transgenic ,Microscopy ,Confocal ,Neoplasm Transplantation ,Neovascularization ,Pathologic ,Osteosarcoma ,GREEN FLUORESCENT PROTEIN ,RED FLUORESCENT PROTEIN ,OSTEOSARCOMA ,ANGIOGENESIS ,GELFOAM ,NESTIN ,TRANSGENIC NUDE MOUSE ,CONFOCAL MICROSCOPY ,GELFOAM® ,Medical Physiology ,Biochemistry & Molecular Biology ,Biochemistry and cell biology - Abstract
We previously described a color-coded imaging model that can quantify the length of nascent blood vessels using Gelfoam® implanted in nestin-driven green fluorescent protein (ND-GFP) nude mice. In ND-GFP mice, nascent blood vessels are labeled with GFP. We report here that osteosarcoma cells promote angiogenesis in the Gelfoam® angiogenesis assay in ND-GFP mice. Gelfoam® was initially transplanted subcutaneously in the flank of transgenic ND-GFP nude mice. Seven days after transplantation of Gelfoam®, skin flaps were made and human 143B osteosarcoma cells expressing green fluorescent protein (GFP) in the nucleus and red fluorescent protein (RFP) in cytoplasm were injected into the transplanted Gelfoam®. The control-group mice had only implanted Gelfoam®. Skin flaps were made at days 14, 21, and 28 after transplantation of the Gelfoam® to allow imaging of vascularization in the Gelfoam® using a variable-magnification small animal imaging system and confocal fluorescence microscopy. ND-GFP expressing nascent blood vessels penetrated and spread into the Gelfoam® in a time-dependent manner in both control and osteosarcoma-implanted mice. ND-GFP expressing blood vessels in the Gelfoam® of the osteosarcoma-implanted mice were associated with the cancer cells and larger and longer than in the Gelfoam®-only implanted mice (P
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- 2014
31. Selective methioninase-induced trap of cancer cells in S/G2 phase visualized by FUCCI imaging confers chemosensitivity.
- Author
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Yano, Shuya, Li, Shukuan, Han, Qinghong, Tan, Yuying, Bouvet, Michael, Fujiwara, Toshiyoshi, and Hoffman, Robert M
- Subjects
Hela Cells ,Humans ,Breast Neoplasms ,Carbon-Sulfur Lyases ,Recombinant Proteins ,Antimetabolites ,Antineoplastic ,Antineoplastic Combined Chemotherapy Protocols ,Microscopy ,Confocal ,Microscopy ,Fluorescence ,Transfection ,Drug Resistance ,Neoplasm ,Genes ,Reporter ,Time Factors ,Uterine Cervical Neoplasms ,Female ,S Phase Cell Cycle Checkpoints ,MCF-7 Cells ,HeLa Cells ,cell cycle ,FUCCI ,imaging ,S/G(2) phase block ,recombinant methioninase ,rMETase ,chemotherapy ,HeLa cells ,MCF-7 cells ,Antimetabolites ,Antineoplastic ,Drug Resistance ,Neoplasm ,Genes ,Reporter ,Microscopy ,Confocal ,Fluorescence ,Oncology and Carcinogenesis - Abstract
A major impediment to the response of tumors to chemotherapy is that the large majority of cancer cells within a tumor are quiescent in G0/G1, where cancer cells are resistant to chemotherapy. To attempt to solve this problem of quiescent cells in a tumor, cancer cells were treated with recombinant methioninase (rMETase), which selectively traps cancer cells in S/G2. The cell cycle phase of the cancer cells was visualized with the fluorescence ubiquitination-based cell cycle indicator cell cycle indicator (FUCCI). At the time of rMETase-induced S/G2-phase blockage, identified by the cancer cells' green fluorescence by FUCCI imaging, the cancer cells were administered S/G2-dependent chemotherapy drugs, which interact with DNA or block DNA synthesis such as doxorubicin, cisplatin, or 5-fluorouracil. Treatment of cancer cells with drugs only, without rMETase-induced S/G2 phase blockage, led to the majority of the cancer-cell population being blocked in G0/G1 phase, identified by the cancer cells becoming red fluorescent in the FUCCI system. The G0/G1 blocked cells were resistant to the chemotherapy. In contrast, trapping of cancer cells in S/G2 phase by rMETase treatment followed by FUCCI-imaging-guided chemotherapy was highly effective in killing the cancer cells.
- Published
- 2014
32. Tumor-targeting Salmonella typhimurium A1-R prevents experimental human breast cancer bone metastasis in nude mice
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Miwa, Shinji, Yano, Shuya, Zhang, Yong, Matsumoto, Yasunori, Uehara, Fuminari, Yamamoto, Mako, Hiroshima, Yukihiko, Kimura, Hiroaki, Hayashi, Katsuhiro, Yamamoto, Norio, Bouvet, Michael, Tsuchiya, Hiroyuki, Hoffman, Robert M, and Zhao, Ming
- Subjects
Cancer ,Vaccine Related ,Breast Cancer ,Prevention ,Emerging Infectious Diseases ,Aetiology ,2.1 Biological and endogenous factors ,Animals ,Bone Neoplasms ,Breast Neoplasms ,Female ,Humans ,Mice ,Mice ,Nude ,Salmonella typhimurium ,Xenograft Model Antitumor Assays ,breast cancer ,bone metastasis ,GFP ,RFP ,bacterial therapy ,Salmonella typhimurium A1-R ,Oncology and Carcinogenesis - Abstract
Bone metastasis is a lethal and morbid late stage of breast cancer that is currently treatment resistant. More effective mouse models and treatment are necessary. High bone-metastatic variants of human breast cancer cells were selected in nude mice by cardiac injection. After cardiac injection of a high bone-metastatic variant of breast cancer, all untreated mice had bone metastases compared to only 20% with parental cells. Treatment with tumor-targeting Salmonella typhimurium A1-R completely prevented the appearance of bone metastasis of the high metastatic variant in nude mice (P < 0.001). After injection of the highly bone-metastatic breast cancer variant to the tibia of nude mice, S. typhimurium A1-R treatment significantly reduced tumor growth in the bone (P < 0.001). These data indicated that S. typhimurium A1-R is useful to prevent and inhibit breast cancer bone metastasis and should be of future clinical use for breast cancer in the adjuvant setting.
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- 2014
33. Spatial–temporal FUCCI imaging of each cell in a tumor demonstrates locational dependence of cell cycle dynamics and chemoresponsiveness
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Yano, Shuya, Zhang, Yong, Miwa, Shinji, Tome, Yasunori, Hiroshima, Yukihiko, Uehara, Fuminari, Yamamoto, Mako, Suetsugu, Atsushi, Kishimoto, Hiroyuki, Tazawa, Hiroshi, Zhao, Ming, Bouvet, Michael, Fujiwara, Toshiyoshi, and Hoffman, Robert M
- Subjects
Cancer ,Adenocarcinoma ,Animals ,Antineoplastic Agents ,Cell Cycle ,Cell Line ,Tumor ,Cisplatin ,Heterografts ,Humans ,Liver Neoplasms ,Mice ,Nude ,Neoplasm Transplantation ,Optical Imaging ,Paclitaxel ,Spatio-Temporal Analysis ,drug resistance ,cell cycle ,tumor ,confocal laser microscopy ,fluorescent proteins ,FUCCI ,tumor blood vessels ,dormancy ,Biochemistry and Cell Biology ,Developmental Biology - Abstract
The phase of the cell cycle can determine whether a cancer cell can respond to a given drug. We report here on the results of monitoring of real-time cell cycle dynamics of cancer cells throughout a live tumor intravitally using a fluorescence ubiquitination cell cycle indicator (FUCCI) before, during, and after chemotherapy. In nascent tumors in nude mice, approximately 30% of the cells in the center of the tumor are in G₀/G₁ and 70% in S/G₂/M. In contrast, approximately 90% of cancer cells in the center and 80% of total cells of an established tumor are in G₀/G₁ phase. Similarly, approximately 75% of cancer cells far from (> 100 µm) tumor blood vessels of an established tumor are in G₀/G₁. Longitudinal real-time imaging demonstrated that cytotoxic agents killed only proliferating cancer cells at the surface and, in contrast, had little effect on quiescent cancer cells, which are the vast majority of an established tumor. Moreover, resistant quiescent cancer cells restarted cycling after the cessation of chemotherapy. Our results suggest why most drugs currently in clinical use, which target cancer cells in S/G₂/M, are mostly ineffective on solid tumors. The results also suggest that drugs that target quiescent cancer cells are urgently needed.
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- 2014
34. Successful Fluorescence-Guided Surgery on Human Colon Cancer Patient-Derived Orthotopic Xenograft Mouse Models Using a Fluorophore-Conjugated Anti-CEA Antibody and a Portable Imaging System
- Author
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Hiroshima, Yukihiko, Maawy, Ali, Metildi, Cristina A, Zhang, Yong, Uehara, Fuminari, Miwa, Shinji, Yano, Shuya, Sato, Sho, Murakami, Takashi, Momiyama, Masashi, Chishima, Takashi, Tanaka, Kuniya, Bouvet, Michael, Endo, Itaru, and Hoffman, Robert M
- Subjects
Biotechnology ,Cancer ,Colo-Rectal Cancer ,Digestive Diseases ,Animals ,Antibodies ,Anti-Idiotypic ,Carcinoembryonic Antigen ,Colonic Neoplasms ,Disease Models ,Animal ,Female ,Humans ,Hydrazines ,Mice ,Mice ,Nude ,Mice ,SCID ,Optical Imaging ,Surgery ,Computer-Assisted ,Transplantation ,Heterologous ,Clinical Sciences ,Pediatrics ,Surgery - Abstract
BackgroundFluorescence-guided surgery (FGS) can enable successful cancer surgery where bright-light surgery often cannot. There are three important issues for FGS going forward toward the clinic: (a) proper tumor labeling, (b) a simple portable imaging system for the operating room, and (c) patient-like mouse models in which to develop the technology. The present report addresses all three.Materials and methodsPatient colon tumors were initially established subcutaneously in nonobese diabetic (NOD)/severe combined immune deficiency (SCID) mice immediately after surgery. The tumors were then harvested from NOD/SCID mice and passed orthotopically in nude mice to make patient-derived orthotopic xenograft (PDOX) models. Eight weeks after orthotopic implantation, a monoclonal anti-carcinoembryonic antigen (CEA) antibody conjugated with AlexaFluor 488 (Molecular Probes Inc., Eugene, OR) was delivered to the PDOX models as a single intravenous dose 24 hours before laparotomy. A hand-held portable fluorescence imaging device was used.ResultsThe primary tumor was clearly visible at laparotomy with the portable fluorescence imaging system. Frozen section microscopy of the resected specimen demonstrated that the anti-CEA antibody selectively labeled cancer cells in the colon cancer PDOX. The tumor was completely resected under fluorescence navigation. Histologic evaluation of the resected specimen demonstrated that cancer cells were not present in the margins, indicating successful tumor resection. The FGS animals remained tumor free for over 6 months.ConclusionsThe results of the present report indicate that FGS using a fluorophore-conjugated anti-CEA antibody and portable imaging system improves efficacy of resection for CEA-positive colorectal cancer. These data provide the basis for clinical trials.
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- 2014
35. Hand-held high-resolution fluorescence imaging system for fluorescence-guided surgery of patient and cell-line pancreatic tumors growing orthotopically in nude mice
- Author
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Hiroshima, Yukihiko, Maawy, Ali, Sato, Sho, Murakami, Takashi, Uehara, Fuminari, Miwa, Shinji, Yano, Shuya, Momiyama, Masashi, Chishima, Takashi, Tanaka, Kuniya, Bouvet, Michael, Endo, Itaru, and Hoffman, Robert M
- Subjects
Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Cancer ,Bioengineering ,Rare Diseases ,Animals ,Antigens ,Tumor-Associated ,Carbohydrate ,Carcinoembryonic Antigen ,Cell Line ,Tumor ,Disease Models ,Animal ,Fluorescent Antibody Technique ,Fluorescent Dyes ,Green Fluorescent Proteins ,Humans ,Image Enhancement ,Mice ,Mice ,Nude ,Microscopy ,Fluorescence ,Neoplasm Transplantation ,Neoplasm ,Residual ,Pancreatic Neoplasms ,Surgery ,Computer-Assisted ,Transplantation ,Heterologous ,Fluorescent proteins ,Pancreatic cancer ,CEA ,CA19-9 ,Patient-derived orthotopic xenografts (PDOX ((R))) ,Cell line ,Mouse model ,In vivo imaging ,Fluorescence-guided surgery ,In vivo imaging ,Patient-derived orthotopic xenografts (PDOX(®)) ,Clinical Sciences ,Surgery ,Clinical sciences - Abstract
BackgroundIn this study, we investigated the advantages of fluorescence-guided surgery (FGS) in mice of a portable hand-sized imaging system compared with a large fluorescence imaging system or a long-working-distance fluorescence microscope.MethodsMouse models of human pancreatic cancer for FGS included the following: (1) MiaPaCa-2-expressing green fluorescent protein, (2) BxPC3 labeled with Alexa Fluor 488-conjucated anti-carcinoembryonic antigen (CEA) antibody, and (3) patient-derived orthotopic xenograft (PDOX) labeled with Alexa Fluor 488-conjugated anti-carbohydrate antigen 19-9 antibody.ResultsEach device could clearly detect the primary MiaPaCa-2-green fluorescent protein tumor and any residual tumor after FGS. In the BxPC3 model labeled with Alexa Fluor 488-conjugated anti-CEA, each device could detect the primary tumor, but the MVX10 could not clearly detect the residual tumor remaining after FGS whereas the other devices could. In the PDOX model labeled with Alexa Fluor 488-conjugated anti-carbohydrate antigen 19-9, only the portable hand-held device could distinguish the residual tumor from the background, and complete resection of the residual tumor was achieved under fluorescence navigation.ConclusionsThe results described in the present report suggest that the hand-held mobile imaging system can be applied to the clinic for FGS because of its convenient size and high sensitivity which should help make FGS widely used.
- Published
- 2014
36. Color-coded chemotherapy: S/G2-phase-trapping by methioninase pre-treatment, indicated by FUCCI imaging, enables highly effective cancer chemotherapy
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Yano, Shuya, Tome, Yasunori, Digman, Michelle, Momiyama, Masashi, Suetsugu, Atsushi, Gratton, Enrico, and Hoffman, Robert
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Biochemistry & Molecular Biology ,Biochemistry and Cell Biology ,Physiology ,Medical Physiology - Published
- 2014
37. Invading cancer cells are predominantly in G0/G1 resulting in chemoresistance demonstrated by real-time FUCCI imaging
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Yano, Shuya, Miwa, Shinji, Mii, Sumiyuki, Hiroshima, Yukihiko, Uehara, Fuminari, Yamamoto, Mako, Kishimoto, Hiroyuki, Tazawa, Hiroshi, Bouvet, Michael, Fujiwara, Toshiyoshi, and Hoffman, Robert M
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Cancer ,Aetiology ,2.1 Biological and endogenous factors ,Adenocarcinoma ,Antineoplastic Agents ,Cell Line ,Tumor ,Cell Movement ,Cisplatin ,Drug Resistance ,Neoplasm ,G1 Phase ,Gelatin Sponge ,Absorbable ,Green Fluorescent Proteins ,Humans ,Luminescent Proteins ,Microscopy ,Confocal ,Neoplasm Invasiveness ,Resting Phase ,Cell Cycle ,Stomach Neoplasms ,cancer invasion ,cell cycle kinetics ,fluorescent proteins ,FUCCI ,3D ,Gelfoam (R) histoculture ,confocal laser microscopy ,real-time imaging ,Gelfoam histoculture ,Biochemistry and Cell Biology ,Developmental Biology - Abstract
Invasive cancer cells are a critical target in order to prevent metastasis. In the present report, we demonstrate real-time visualization of cell cycle kinetics of invading cancer cells in 3-dimensional (3D) Gelfoam® histoculture, which is in vivo-like. A fluorescence ubiquitination cell cycle indicator (FUCCI) whereby G0/G1 cells express a red fluorescent protein and S/G2/M cells express a green fluorescent protein was used to determine the cell cycle position of invading and non-invading cells. With FUCCI 3D confocal imaging, we observed that cancer cells in G0/G1 phase in Gelfoam® histoculture migrated more rapidly and further than cancer cells in S/G2/M phases. Cancer cells ceased migrating when they entered S/G2/M phases and restarted migrating after cell division when the cells re-entered G0/G1. Migrating cancer cells also were resistant to cytotoxic chemotherapy, since they were preponderantly in G0/G1, where cytotoxic chemotherapy is not effective. The results of the present report suggest that novel therapy targeting G0/G1 cancer cells should be developed to prevent metastasis.
- Published
- 2014
38. The tumor-educated-macrophage increase of malignancy of human pancreatic cancer is prevented by zoledronic acid.
- Author
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Hiroshima, Yukihiko, Maawy, Ali, Hassanein, Mohamed K, Menen, Rhiana, Momiyama, Masashi, Murakami, Takashi, Miwa, Shinji, Yamamoto, Mako, Uehara, Fuminari, Yano, Shuya, Mori, Ryutaro, Matsuyama, Ryusei, Chishima, Takashi, Tanaka, Kuniya, Ichikawa, Yasushi, Bouvet, Michael, Endo, Itaru, and Hoffman, Robert M
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Cell Line ,Tumor ,Macrophages ,Animals ,Humans ,Mice ,Pancreatic Neoplasms ,Disease Models ,Animal ,Disease Progression ,Diphosphonates ,Imidazoles ,Cell Communication ,Mitosis ,Cell Proliferation ,Heterografts ,Zoledronic Acid ,Cell Line ,Tumor ,Disease Models ,Animal ,General Science & Technology - Abstract
We previously defined macrophages harvested from the peritoneal cavity of nude mice with subcutaneous human pancreatic tumors as "tumor-educated-macrophages" (Edu) and macrophages harvested from mice without tumors as "naïve-macrophages" (Naïve), and demonstrated that Edu-macrophages promoted tumor growth and metastasis. In this study, Edu- and Naïve-macrophages were compared for their ability to enhance pancreatic cancer malignancy at the cellular level in vitro and in vivo. The inhibitory efficacy of Zoledronic acid (ZA) on Edu-macrophage-enhanced metastasis was also determined. XPA1 human pancreatic cancer cells in Gelfoam co-cultured with Edu-macrophages proliferated to a greater extent compared to XPA1 cells cultured with Naïve-macrophages (P = 0.014). XPA1 cells exposed to conditioned medium harvested from Edu culture significantly increased proliferation (P = 0.016) and had more migration stimulation capability (P
- Published
- 2014
39. Fluorescence-guided surgery in combination with UVC irradiation cures metastatic human pancreatic cancer in orthotopic mouse models.
- Author
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Hiroshima, Yukihiko, Maawy, Ali, Zhang, Yong, Sato, Sho, Murakami, Takashi, Yamamoto, Mako, Uehara, Fuminari, Miwa, Shinji, Yano, Shuya, Momiyama, Masashi, Chishima, Takashi, Tanaka, Kuniya, Bouvet, Michael, Endo, Itaru, and Hoffman, Robert M
- Subjects
Cell Line ,Tumor ,Animals ,Humans ,Mice ,Mice ,Nude ,Pancreatic Neoplasms ,Neoplasm Recurrence ,Local ,Neoplasm ,Residual ,Disease Progression ,Green Fluorescent Proteins ,Combined Modality Therapy ,Ultraviolet Therapy ,Surgery ,Computer-Assisted ,Xenograft Model Antitumor Assays ,Transfection ,Fluorescence ,Optical Imaging ,Cell Line ,Tumor ,Nude ,Neoplasm Recurrence ,Local ,Neoplasm ,Residual ,Surgery ,Computer-Assisted ,General Science & Technology - Abstract
The aim of this study is to determine if ultraviolet light (UVC) irradiation in combination with fluorescence-guided surgery (FGS) can eradicate metastatic human pancreatic cancer in orthotopic nude-mouse models. Two weeks after orthotopic implantation of human MiaPaCa-2 pancreatic cancer cells, expressing green fluorescent protein (GFP), in nude mice, bright-light surgery (BLS) was performed on all tumor-bearing mice (n = 24). After BLS, mice were randomized into 3 treatment groups; BLS-only (n = 8) or FGS (n = 8) or FGS-UVC (n = 8). The residual tumors were resected using a hand-held portable imaging system under fluorescence navigation in mice treated with FGS and FGS-UVC. The surgical resection bed was irradiated with 2700 J/m2 UVC (254 nm) in the mice treated with FGS-UVC. The average residual tumor area after FGS (n = 16) was significantly smaller than after BLS only (n = 24) (0.135±0.137 mm2 and 3.338±2.929 mm2, respectively; p = 0.007). The BLS treated mice had significantly reduced survival compared to FGS- and FGS-UVC-treated mice for both relapse-free survival (RFS) (p
- Published
- 2014
40. Precise recurrence-free fluorescence-guided surgery with color-coded cancer and stromal cells in a patient-derived orthotopic xenograft model of pancreatic cancer
- Author
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Hoffman, Robert M., primary, Yano, Shuya, additional, Nishino, Hiroto, additional, and Bouvet, Michael, additional
- Published
- 2020
- Full Text
- View/download PDF
41. Comparison of fluorescence-labeling strategies of colon cancer for fluorescence-guided surgery of liver metastasis in orthotopic mouse models
- Author
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Hoffman, Robert M., primary, Murakami, Takashi, additional, Yano, Shuya, additional, Hiroshima, Yukihiko, additional, Nishino, Hiroto, additional, and Bouvet, Michael, additional
- Published
- 2020
- Full Text
- View/download PDF
42. List of contributors
- Author
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Aleman, Rene, primary, Aoki, Takeshi, additional, Bouvet, Michael, additional, Cao, Hop S. Tran, additional, Choyke, Peter L., additional, Dip, Fernando, additional, Durkin, Claire, additional, Falco, Jorge, additional, Gioux, Sylvain, additional, Hiroshima, Yukihiko, additional, Ho, Jason, additional, Hoffman, Robert M., additional, Hollandsworth, Hannah M., additional, Ishizawa, Takeaki, additional, Kawaguchi, Yoshikuni, additional, Kobayashi, Hisataka, additional, Koizumi, Tomotake, additional, Krishna, Somashekar G., additional, Kuasano, Tomokazu, additional, Mansour, Doaa A., additional, Menzo, Emanuele Lo, additional, Metildi, Cristina A., additional, Miwa, Shinji, additional, Murakami, Masahiko, additional, Murakami, Takashi, additional, Nagaya, Tadanobu, additional, Nakamura, Yu A., additional, Nishino, Hiroto, additional, Oyefule, Omobolanle, additional, Rosenthal, Raul J., additional, Roy, Mayank, additional, Saiura, Akio, additional, Szomstein, Samuel, additional, Takahashi, Naoto, additional, Tashiro, Yoshihiko, additional, Turner, Michael, additional, Uehara, Fuminari, additional, and Yano, Shuya, additional
- Published
- 2020
- Full Text
- View/download PDF
43. The Use of Patient-Derived Orthotopic Xenograft (PDOX) Models to Develop Curative Fluorescence-Guided Surgery of Cancer
- Author
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Hoffman, Robert M., Hiroshima, Yukihiko, Yano, Shuya, Metildi, Cristina A., Bouvet, Michael, Coleman, William B., Series editor, Tsongalis, Gregory J., Series editor, and Hoffman, Robert M., editor
- Published
- 2017
- Full Text
- View/download PDF
44. Fluorescence Imaging of Tumors in Human Patient-Derived Orthotopic Xenograft (PDOX) Mouse Models
- Author
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Hoffman, Robert M., Suetsugu, Atsushi, Kiyuna, Tasuku, Yano, Shuya, Bouvet, Michael, Coleman, William B., Series editor, Tsongalis, Gregory J., Series editor, and Hoffman, Robert M., editor
- Published
- 2017
- Full Text
- View/download PDF
45. Comparison of efficacy of Salmonella typhimurium A1-R and chemotherapy on stem-like and non-stem human pancreatic cancer cells
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Hiroshima, Yukihiko, Zhao, Ming, Zhang, Yong, Maawy, Ali, Hassanein, Mohamed, Uehara, Fuminari, Miwa, Shinji, Yano, Shuya, Momiyama, Masashi, Suetsugu, Atsushi, Chishima, Takashi, Tanaka, Kuniya, Bouvet, Michael, Endo, Itaru, and Hoffman, Robert M
- Subjects
Rare Diseases ,Digestive Diseases ,Cancer ,Stem Cell Research - Nonembryonic - Human ,Stem Cell Research - Nonembryonic - Non-Human ,Pancreatic Cancer ,Orphan Drug ,Stem Cell Research ,Animals ,Antineoplastic Agents ,Antineoplastic Combined Chemotherapy Protocols ,Cell Line ,Tumor ,Drug Resistance ,Neoplasm ,Humans ,Mice ,Mice ,Nude ,Microscopy ,Confocal ,Neoplastic Stem Cells ,Pancreatic Neoplasms ,Salmonella typhimurium ,Treatment Outcome ,Xenograft Model Antitumor Assays ,GFP ,RFP ,amino acid auxotrophy ,chemoresistance ,confocal microscopy ,fluorescence imaging ,pancreatic cancer ,selective tumor targeting ,stem cell ,Biochemistry and Cell Biology ,Developmental Biology - Abstract
The XPA1 human pancreatic cancer cell line is dimorphic, with spindle stem-like cells and round non-stem cells. We report here the in vitro IC 50 values of stem-like and non-stem XPA1 human pancreatic cells cells for: (1) 5-fluorouracil (5-FU), (2) cisplatinum (CDDP), (3) gemcitabine (GEM), and (4) tumor-targeting Salmonella typhimurium A1-R (A1-R). IC 50 values of stem-like XPA1 cells were significantly higher than those of non-stem XPA1 cells for 5-FU (P = 0.007) and CDDP (P = 0.012). In contrast, there was no difference between the efficacy of A1-R on stem-like and non-stem XPA1 cells. In vivo, 5-FU and A1-R significantly reduced the tumor weight of non-stem XPA1 cells (5-FU; P = 0.028; A1-R; P = 0.011). In contrast, only A1-R significantly reduced tumor weight of stem-like XPA1 cells (P = 0.012). The combination A1-R with 5-FU improved the antitumor efficacy compared with 5-FU monotherapy on the stem-like cells (P = 0.004). The results of the present report indicate A1-R is a promising therapy for chemo-resistant pancreatic cancer stem-like cells.
- Published
- 2013
46. Abstract 3412: Imaging of methioninase-induced S/G2-phase-trapping for subsequent effective chemotherapy.
- Author
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Yano, Shuya, Tome, Yasunori, Digman, Michelle, Momiyama, Masashi, Suetsugu, Atsushi, Gratton, Enrico, and Hoffman, Robert M
- Subjects
Cancer ,Oncology and Carcinogenesis ,Oncology & Carcinogenesis - Abstract
Abstract Methionine-dependence of cancer cells may be due to excessive methylation reactions in cancer cells. Deprivation of methionine α,γ lyase (methioninase or METase) selectively arrests cancer cells during late S-phase, where they are highly sensitive to DNA-damaging chemotherapy. Fluorescent ubiquitination-based cell cycle indicator (FUCCI)), was used to monitor the onset of the S/G2-phase block due to methionine deprivation effected by METase. The S-phase-blocked cancer cells fluoresced yellow or green, in contrast to cancer cells in G1 which fluoresced red. Cancer cells, synchronously blocked in S-phase by METase and identified by their yellow-green fluorescence, were administered DNA-damaging chemotherapy drugs such as doxorubicin, cisplatin, or 5-fluorouracil. Treatment of cancer cells with drugs only without methioninase-effected S-phase synchrony, led to the majority of the cancer cell population being blocked in G0/G1 phase (red fluorescent) where they were resistant to the drugs. In contrast, METase treatment, followed by chemotherapy when FUCCI indicated the S/G2 block was highly effective for killing cancer cells. Color-coded chemotherapy, whereby the cell cycle of cancer cells is selectively and synchronously blocked in S-phase as identified by fluorescent reporters, may be a general approach to effective cancer treatment. Citation Format: Shuya Yano, Yasunori Tome, Michelle Digman, Masashi Momiyama, Atsushi Suetsugu, Enrico Gratton, Robert M. Hoffman. Imaging of methioninase-induced S/G2-phase-trapping for subsequent effective chemotherapy. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3412. doi:10.1158/1538-7445.AM2013-3412
- Published
- 2013
47. Imaging of methioninase-induced S/G(2)-phase-trapping for subsequent effective chemotherapy
- Author
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Yano, Shuya, Tome, Yasunori, Digman, Michelle, Momiyamal, Masashi, Suetsugu, Atsushi, Gratton, Enrico, and Hoffman, Robert M
- Subjects
Oncology & Carcinogenesis ,Oncology and Carcinogenesis - Published
- 2013
48. GFP labeling kinetics of triple-negative human breast cancer by a killer-reporter adenovirus in 3D Gelfoam® histoculture
- Author
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Yano, Shuya, Takehara, Kiyoto, Miwa, Shinji, Kishimoto, Hiroyuki, Tazawa, Hiroshi, Urata, Yasuo, Kagawa, Shunsuke, Bouvet, Michael, Fujiwara, Toshiyoshi, and Hoffman, Robert M.
- Published
- 2017
49. High-metastatic triple-negative breast-cancer variants selected in vivo become chemoresistant in vitro
- Author
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Yano, Shuya, Takehara, Kiyoto, Kishimoto, Hiroyuki, Tazawa, Hiroshi, Urata, Yasuo, Kagawa, Shunsuke, Bouvet, Michael, Fujiwara, Toshiyoshi, and Hoffman, Robert M.
- Published
- 2017
50. Comparison of in vitro invasiveness of high- and low-metastatic triple-negative human breast cancer visualized by color-coded imaging
- Author
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Yano, Shuya, Takehara, Kiyoto, Tazawa, Hiroshi, Kishimoto, Hiroyuki, Kagawa, Shunsuke, Fujiwara, Toshiyoshi, and Hoffman, Robert M.
- Published
- 2017
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