Genomes and Genes
R M Hoffman
Affiliation: AntiCancer Inc
- Hasegawa K, Suetsugu A, Nakamura M, Matsumoto T, Aoki H, Kunisada T, et al. Imaging Nuclear-Cytoplasmic Dynamics in Primary and Metastatic Colon Cancer in Nude Mice. Anticancer Res. 2016;36:2113-7 pubmed..Our results demonstrate a similar heterogeneity of nuclear-cytoplasmic dynamics within primary tumors and metastases, which may be an important factor in the stochastic nature of metastasis. ..
- Matsumoto T, Suetsugu A, Hasegawa K, Nakamura M, Shibata Y, Aoki H, et al. A Mouse Model of Fluorescent Protein-expressing Disseminated Peritoneal Lymphoma for Fluorescence-guided Surgery. Anticancer Res. 2016;36:4483-7 pubmed..The present report indicates the feasibility of FGS of peritoneally-disseminated cancer. ..
- Igarashi K, Yamamoto N, Hayashi K, Takeuchi A, Kimura H, Miwa S, et al. Non-toxic Efficacy of the Combination of Caffeine and Valproic Acid on Human Osteosarcoma Cells In Vitro and in Orthotopic Nude-mouse Models. Anticancer Res. 2016;36:4477-82 pubmed
- Igarashi K, Kawaguchi K, Kiyuna T, Miyake K, Murakami T, Yamamoto N, et al. Effective Metabolic Targeting of Human Osteosarcoma Cells In Vitro and in Orthotopic Nude-mouse Models with Recombinant Methioninase. Anticancer Res. 2017;37:4807-4812 pubmed..Future studies will investigate the efficacy of rMETase on patient-derived orthotopic xenograft (PDOX) models of osteosarcoma as a bridge to testing rMETase in the clinic. ..
- Hoffman R, Mii S, Duong J, Amoh Y. Nerve Growth and Interaction in GelfoamÂ® Histoculture: A Nervous System Organoid. Methods Mol Biol. 2018;1760:163-186 pubmed publisher..HAP stem cell proliferation resulted in elongation of the follicle nerve and interaction with other nerves in 3D GelfoamÂ® histoculture, including the sciatic nerve, trigeminal nerve, and trigeminal nerve ganglion. ..
- Hoffman R. Nestin-driven green fluorescent protein as an imaging marker for nascent blood vessels in mouse models of cancer. Methods Mol Biol. 2011;689:183-204 pubmed publisher..These fluorescent models can be used to study the early events of angiogenesis and to quantitatively determine efficacy of antiangiogenesis compounds. ..
- Hoffman R, Yang M. Color-coded fluorescence imaging of tumor-host interactions. Nat Protoc. 2006;1:928-35 pubmed..The 'color-coded' tumor-host models enable imaging and therefore a deeper understanding of the host cells involved and their function in tumor progression. Approximately 4-8 weeks are needed for these procedures. ..
- Kawaguchi K, Miyake K, Han Q, Li S, Tan Y, Igarashi K, et al. Oral recombinant methioninase (o-rMETase) is superior to injectable rMETase and overcomes acquired gemcitabine resistance in pancreatic cancer. Cancer Lett. 2018;432:251-259 pubmed publisher..The present study shows that o-rMETase is effective and overcomes acquired GEM resistance in pancreatic cancer and demonstrates the clinical potential of this strategy. ..
- Kawaguchi K, Igarashi K, Miyake K, Lwin T, Miyake M, Kiyuna T, et al. MEK inhibitor trametinib in combination with gemcitabine regresses a patient-derived orthotopic xenograft (PDOX) pancreatic cancer nude mouse model. Tissue Cell. 2018;52:124-128 pubmed publisher..However, GEM?+?TRA inhibited the PDOX tumor growth significantly greater than TRA alone. These results suggest the clinical potential of the combination of TRA and GEM for pancreatic cancer. ..
- Hoffman R, Yano S. In Vivo-Like Cell-Cycle Phase Distribution of Cancer Cells in GelfoamÂ® Histoculture Observed in Real Time by FUCCI Imaging. Methods Mol Biol. 2018;1760:109-123 pubmed publisher..In 2D culture, cancer cells were much more chemosensitive. These results indicate why the drug response pattern of tumors in GelfoamÂ® histoculture reflects what is observed in vivo. ..
- Hoffman R. Human Hair Follicle Associated-Pluripotent (hHAP) Stem Cells Differentiate to Cardiac Muscle Cells. Methods Mol Biol. 2018;: pubmed publisher..The methods of this chapter are appropriate for use of human hair follicles to produce hHAP stem cells in sufficient quantities for future heart, nerve, and spinal cord regeneration in the clinic. ..
- Igarashi K, Kawaguchi K, Kiyuna T, Miyake K, Miyake M, Singh A, et al. Tumor-targeting Salmonella typhimurium A1-R is a highly effective general therapeutic for undifferentiated soft tissue sarcoma patient-derived orthotopic xenograft nude-mouse models. Biochem Biophys Res Commun. 2018;497:1055-1061 pubmed publisher..These results suggest that S.Â typhimurium A1-R can be a general therapeutic for USTS and possibly sarcoma in general. ..
- Hoffman R. Diagnosis and Pathological Analysis of Patient Cancers by Detection of Proliferating Cells in GelfoamÂ® Histoculture. Methods Mol Biol. 2018;1760:49-60 pubmed publisher..Normal tissues can also proliferate at high rates. Mean growth fraction index (GFI) was highest for patient tumors with the pure subtype of small-cell lung cancer than other types of lung cancer. ..
- Suetsugu A, Snyder C, Moriwaki H, Saji S, Bouvet M, Hoffman R. Imaging the Interaction of Pancreatic Cancer and Stellate Cells in the Tumor Microenvironment during Metastasis. Anticancer Res. 2015;35:2545-51 pubmed..Pancreatic cancer cells and stellate stem cells form a very close relationship and accompany each other to distant metastatic sties. Our hypothesis is that pancreatic stellate cells form a niche for metastasis of pancreatic cancer. ..
- Hoffman R. Clinical Usefulness of the Histoculture Drug Response Assay for Prostate Cancer and Benign Prostate Hypertrophy (BPH). Methods Mol Biol. 2018;1760:101-107 pubmed publisher..Genistein decreased the androgen-sensitivity index of BPH and prostate cancer in GelfoamÂ® histoculture in a dose-dependent manner. ..
- Hiroshima Y, Zhang Y, Zhang N, Uehara F, Maawy A, Murakami T, et al. Patient-derived orthotopic xenograft (PDOX) nude mouse model of soft-tissue sarcoma more closely mimics the patient behavior in contrast to the subcutaneous ectopic model. Anticancer Res. 2015;35:697-701 pubmed..In contrast, the majority of the subcutaneously-implanted tumor comprised round to oval cells. These results indicate that the PDOX recapitulated the histology of the original tumor more than the subcutaneous model. ..
- Hoffman R. Orthotopic mouse models of tumor metastasis expressing fluorescent reporters produce imageable circulating tumor cells. Cancer Microenviron. 2014;7:133-8 pubmed publisher..We also describe a facile method to label patient CTCs ex vivo using a telomerase-expressing GFP-containing adenovirus that will allow the CTC studies described in this review to be translated clinically. ..
- Hoffman R, Jung P, Kim M, Nam J. Prospective Clinical Correlation of the Histoculture Drug Response Assay for Ovarian Cancer. Methods Mol Biol. 2018;1760:73-81 pubmed publisher..The true-positive rate was 88%, the true-negative rate was 86%, the sensitivity was 88%, the specificity was 86%, and the accurate prediction rate was 87% when HDRA results were compared to the response of the treated patients. ..
- Hoffman R. Methionine Dependency Determination of Human Patient Tumors in GelfoamÂ® Histoculture. Methods Mol Biol. 2018;1760:125-131 pubmed publisher..This simple method can be used to screen patient tumors for methionine dependence and then subsequentlyÂ apply appropriate chemotherapy for these patients to target this cancer-specific metabolic abnormality. ..
- Liu F, Hoffman R. Hair Follicle-Associated Pluripotent (HAP) Stem Cells in GelfoamÂ® Histoculture for Use in Spinal Cord Repair. Methods Mol Biol. 2018;1760:145-162 pubmed publisher..Twenty-eight days after transplantation with BA or DPÂ HAP stem cells on GelfoamÂ® to the injured area of the spine, the mice recoveredÂ normal locomotion. ..
- Uehara F, Tome Y, Yano S, Miwa S, Mii S, Hiroshima Y, et al. A color-coded imaging model of the interaction of ?v integrin-GFP expressed in osteosarcoma cells and RFP expressing blood vessels in Gelfoam® vascularized in vivo. Anticancer Res. 2013;33:1361-6 pubmed..The observation of the behavior of ?v integrin-GFP and blood vessels will allow further understanding of the role of ?v integrin in cancer cells. ..
- Zhang Y, Zhang N, Zhao M, Hoffman R. Real-time Non-invasive Spectral Imaging of Orthotopic Red Fluorescent Protein-expressing Lung Tumor Growth in Nude Mice. Anticancer Res. 2015;35:3755-9 pubmed..This imageable nude mouse model using surgical orthotopic implantation of lung cancer will be useful for all types of longitudinal studies. ..
- Hoffman R, Chishima T. Imaging the Governing Step of Metastasis in GelfoamÂ® Histoculture. Methods Mol Biol. 2018;1760:215-220 pubmed publisher..The ability to support selective organ colonization in GelfoamÂ® histoculture and visualize tumor progression by GFP fluorescence allows the in vitro study of the governing processes of metastasis. ..
- Hoffman R. Tumor-targeting amino acid auxotrophic Salmonella typhimurium. Amino Acids. 2009;37:509-21 pubmed publisher..Exploitation of the tumor-killing capability of Salmonella has great promise for a new paradigm of cancer therapy. ..
- Suetsugu A, Jiang P, Yang M, Yamamoto N, Moriwaki H, Saji S, et al. The Use of Living Cancer Cells Expressing Green Fluorescent Protein in the Nucleus and Red Fluorescence Protein in the Cytoplasm for Real-time Confocal Imaging of Chromosome and Cytoplasmic Dynamics During Mitosis. Anticancer Res. 2015;35:2553-7 pubmed..The dual color cells will be a useful tool to discover and evaluate novel strategies for killing cancer cells. ..
- Yano S, Miwa S, Kishimoto H, Toneri M, Hiroshima Y, Yamamoto M, et al. Experimental Curative Fluorescence-guided Surgery of Highly Invasive Glioblastoma Multiforme Selectively Labeled With a Killer-reporter Adenovirus. Mol Ther. 2015;23:1182-1188 pubmed publisher..OBP-401-based FGS enabled curative resection of GBM without recurrence for at least 150 days, compared to less than 30 days with BLS. ..
- Yamamoto N, Gupta A, Xu M, Miki K, Tsujimoto Y, Tsuchiya H, et al. Methioninase gene therapy with selenomethionine induces apoptosis in bcl-2-overproducing lung cancer cells. Cancer Gene Ther. 2003;10:445-50 pubmed..rAdMET/SeMET prodrug gene therapy is therefore a promising novel strategy effective against bcl-2 overexpression, which has blocked other gene therapy strategies. ..
- Tome Y, Uehara F, Kanaya F, Hoffman R. Comparison of "Dimensionality" of Cancer Cell Culture in GelfoamÂ® Histoculture and Matrigel. Methods Mol Biol. 2018;1760:205-214 pubmed publisher..When the cancer cells were seeded on GelfoamÂ®, the cells formed 3-dimensional tissue-like structures. These results indicate that GelfoamÂ® histoculture, unlike Matrigelâ„¢ culture, is true 3-dimensional. ..
- Hoffman R, Yang M. Whole-body imaging with fluorescent proteins. Nat Protoc. 2006;1:1429-38 pubmed..Fluorescent protein-based imaging technology can be used for whole-body imaging of fluorescent cells on essentially all organs. The timeline for these experiments varies from 2 days to 2 months. ..
- Zhang Y, Zhang N, Hoffman R, Zhao M. Surgically-Induced Multi-organ Metastasis in an Orthotopic Syngeneic Imageable Model of 4T1 Murine Breast Cancer. Anticancer Res. 2015;35:4641-6 pubmed..The metastatic pattern in the model thus reflected the clinical metastatic pattern of breast cancer and should be of use for discovery and evaluation of novel therapeutics. ..
- Miwa S, Hoffman R. Imaging DNA Repair After UV Irradiation Damage of Cancer Cells in GelfoamÂ® Histoculture. Methods Mol Biol. 2018;1760:199-203 pubmed publisher..Induction of UV-induced 53BP1-GFP focus formation was limited up to a depth of 40 Î¼m in GelfoamÂ®Â histoculture of MiaPaCa-2 cells, indicating this was the depth limit of UVC irradiation. ..
- Hoffman R. Clinical Correlation of the Histoculture Drug Response Assay for Head and Neck Cancer. Methods Mol Biol. 2018;1760:83-92 pubmed publisher..64%), CDDP (86% vs. 64%), or both agents (85% vs. 63%). These results demonstrate the clinical usefulness of the HDRA for head and neck cancer. ..
- Hoffman R, Tanino H. Clinical Usefulness of the Histoculture Drug Response Assay for Breast Cancer. Methods Mol Biol. 2018;1760:93-100 pubmed publisher..There also was a lack of correlation with breast cancer subtype and drug response in the HDRA, further suggesting the importance of individualized treatment for breast cancer patients afforded by the HDRA. ..
- Zhang Y, Hiroshima Y, Ma H, Zhang N, Zhao M, Hoffman R. Complementarity of variable-magnification and spectral-separation fluorescence imaging systems for noninvasive detection of metastasis and intravital detection of single cancer cells in mouse models. Anticancer Res. 2015;35:661-7 pubmed
- Yang M, Jiang P, Hoffman R. Early Reporting of Apoptosis by Real-time Imaging of Cancer Cells Labeled with Green Fluorescent Protein in the Nucleus and Red Fluorescent Protein in the Cytoplasm. Anticancer Res. 2015;35:2539-43 pubmed..The dual-color cell real-time imaging assay is a more sensitive and earlier reporter for apoptosis than the DNA fragmentation assay. ..
- Hoffman R. Back to the Future: Are Tumor-Targeting Bacteria the Next-Generation Cancer Therapy?. Methods Mol Biol. 2015;1317:239-60 pubmed publisher..A new concept using Salmonella typhimurium A1-R for cell cycle "decoy" chemotherapy of metastatic cancer is also described. ..
- Uchugonova A, Zhang Y, Salz R, Liu F, Suetsugu A, Zhang L, et al. Imaging the Different Mechanisms of Prostate Cancer Cell-killing by Tumor-targeting Salmonella typhimurium A1-R. Anticancer Res. 2015;35:5225-9 pubmed..Understanding the various mechanisms of cancer-cell killing by S. typhimurium A1-R will be important for its use as a general therapeutic for cancer. ..
- Hoffman R. Future of Bacterial Therapy of Cancer. Methods Mol Biol. 2016;1409:177-84 pubmed publisher..This chapter suggests future clinical applications for S. typhimurium A1-R. ..
- Suetsugu A, Matsumoto T, Hasegawa K, Nakamura M, Kunisada T, Shimizu M, et al. Color-coded Live Imaging of Heterokaryon Formation and Nuclear Fusion of Hybridizing Cancer Cells. Anticancer Res. 2016;36:3827-31 pubmed..The ability to image the complex processes following cell fusion using reciprocal color-coded cancer cells will allow greater understanding of the genetic basis of malignancy. ..
- Hoffman R, Bouvet M. Imaging the microenvironment of pancreatic cancer patient-derived orthotopic xenografts (PDOX) growing in transgenic nude mice expressing GFP, RFP, or CFP. Cancer Lett. 2016;380:349-55 pubmed publisher..This model enables powerful color-coded imaging of the interaction of cancer and stromal cells during tumor progression and treatment. ..
- Hoffman R, Kajiura S, Cao W, Liu F, Amoh Y. Cryopreservation of Hair-Follicle Associated Pluripotent (HAP) Stem Cells Maintains Differentiation and Hair-Growth Potential. Adv Exp Med Biol. 2016;951:191-198 pubmed..HAP stem cells can be used for nerve and spinal-cord repair. This biobanking of hair follicles can allow each patient the potential for their own stem cell use for regenerative medicine or hair transplantation. ..
- Miwa S, Toneri M, Igarashi K, Yano S, Kimura H, Hayashi K, et al. Real-Time In Vivo Confocal Fluorescence Imaging of Prostate Cancer Bone-Marrow Micrometastasis Development at the Cellular Level in Nude Mice. J Cell Biochem. 2016;117:2533-7 pubmed publisher..J. Cell. Biochem. 117: 2533-2537, 2016. Â© 2016 Wiley Periodicals, Inc. ..
- Zhang Y, Toneri M, Ma H, Yang Z, Bouvet M, Goto Y, et al. Real-Time GFP Intravital Imaging of the Differences in Cellular and Angiogenic Behavior of Subcutaneous and Orthotopic Nude-Mouse Models of Human PC-3 Prostate Cancer. J Cell Biochem. 2016;117:2546-51 pubmed publisher..These results explain why orthotopic tumors mimimc clinical metastatic tumors in nude mice and why subcutaneous tumors do not. J. Cell. Biochem. 117: 2546-2551, 2016. Â© 2016 Wiley Periodicals, Inc. ..
- Hoffman R, Zhao M. Methods for Tumor Targeting with Salmonella typhimurium A1-R. Methods Mol Biol. 2016;1409:143-64 pubmed publisher..The testing of S. typhimurium A1-R on patient tumors in patient-derived orthotopic xenograft (PDOX) mouse models is also described. The major methodologies described in this chapter should be translatable for clinical studies. ..
- Murakami T, Zhang Y, Wang X, Hiroshima Y, Kasashima H, Yashiro M, et al. Orthotopic Implantation of Intact Tumor Tissue Leads to Metastasis of OCUM-2MD3 Human Gastric Cancer in Nude Mice Visualized in Real Time by Intravital Fluorescence Imaging. Anticancer Res. 2016;36:2125-30 pubmed..These results demonstrate the physiological importance of intact cancer tissue for orthotopic implantation in order for tumors to properly grow and express their metastatic potential. ..
- Cao W, Liu F, Amoh Y, Hoffman R. Protocols for Ectopic Hair Growth from Transplanted Whisker Follicles on the Spinal Cord of Mice. Methods Mol Biol. 2016;1453:137-44 pubmed publisher..This result changes our concept of hair growth, demonstrating it is not limited to the skin and that hair growth appears related to HAP stem cells as both increased in tandem on the spinal cord. ..
- Cao W, Liu F, Amoh Y, Hoffman R. Protocols for Gelfoam(Â®) Histoculture of Hair-Shaft-Producing Mouse Whisker Follicles Containing Nestin-GFP-Expressing Hair-Follicle-Associated Pluripotent (HAP) Stem Cells for Long Time Periods. Methods Mol Biol. 2016;1453:145-50 pubmed publisher..Three-dimensional Gelfoam(Â®) histoculture of hair follicles can provide a very long-term period for evaluating novel agents to promote hair growth. ..
- ..The ND-GFP hair follicle stem cells were later termed hair-follicle-associated pluripotent (HAP) stem cells. ..
- Amoh Y, Katsuoka K, Hoffman R. Peripheral-Nerve and Spinal-Cord Regeneration in Mice Using Hair-Follicle-Associated Pluripotent (HAP) Stem Cells. Methods Mol Biol. 2016;1453:21-32 pubmed publisher..These results suggest that HAP stem cells provide an important accessible, autologous source of adult stem cells for regenerative medicine, that have critical advantages over ES and iPS stem cells. ..
- Igarashi K, Kawaguchi K, Li S, Han Q, Tan Y, Murakami T, et al. Recombinant methioninase in combination with doxorubicin (DOX) overcomes first-line DOX resistance in a patient-derived orthotopic xenograft nude-mouse model of undifferentiated spindle-cell sarcoma. Cancer Lett. 2018;417:168-173 pubmed publisher..The present results demonstrate the power of the PDOX model to identify effective therapy for recalcitrant cancer and the potential of rMETase to overcome DOX resistance. ..
- Hoffman R. Use of fluorescent proteins and color-coded imaging to visualize cancer cells with different genetic properties. Cancer Metastasis Rev. 2016;35:5-19 pubmed publisher..These properties also demonstrate the vast superiority of imaging cancer cells in vivo with fluorescent proteins over photon counting of luciferase-labeled cancer cells. ..
- Tome Y, Yano S, Sugimoto N, Mii S, Uehara F, Miwa S, et al. Use of ?v Integrin Linked to Green Fluorescent Protein in Osteosarcoma Cells and Confocal Microscopy to Image Molecular Dynamics During Lung Metastasis in Nude Mice. Anticancer Res. 2016;36:3811-6 pubmed..The results also suggest a general concept for imaging molecular behavior in vivo. ..
- Yano S, Takehara K, Miwa S, Kishimoto H, Tazawa H, Urata Y, et al. In Vivo Isolation of a Highly-aggressive Variant of Triple-negative Human Breast Cancer MDA-MB-231 Using Serial Orthotopic Transplantation. Anticancer Res. 2016;36:3817-20 pubmed..The availability of a highly invasive variant of TNBC targeting lymph nodes will be very useful for drug discovery of TNBC, a recalcitrant cancer and for mechanistic studies of its aggressiveness. ..
- Tome Y, Uehara F, Miwa S, Yano S, Mii S, Efimova E, et al. Efficacy of the Combination of a PARP Inhibitor and UVC on Cancer Cells as Imaged by Focus Formation by the DNA Repair-related Protein 53BP1 Linked to Green Fluorescent Protein. Anticancer Res. 2016;36:3821-6 pubmed..Confocal microscopy of 53BP1-GFP is a powerful method for imaging UVC-induced DNA damage and repair, as well as inhibition of repair. ..
- Tome Y, Sugimoto N, Yano S, Momiyama M, Mii S, Maehara H, et al. Real-time imaging of ?v integrin molecular dynamics in osteosarcoma cells in vitro and in vivo. Anticancer Res. 2013;33:3021-5 pubmed..These results show that ?v integrin-GFP enables the imaging of the molecular dynamics of ?v integrin in osteosarcoma cells in vitro and in vivo. ..
- Tome Y, Kimura H, Maehara H, Sugimoto N, Bouvet M, Tsuchiya H, et al. High lung-metastatic variant of human osteosarcoma cells, selected by passage of lung metastasis in nude mice, is associated with increased expression of ?(v)?(3) integrin. Anticancer Res. 2013;33:3623-7 pubmed..With this highly metastatic variant overexpressing ?v?3 integrin, it will now be possible to further investigate the mechanism by which ?v?3 integrin facilitates metastasis. ..
- Hoffman R. Patient-Derived Orthotopic Xenograft (PDOX) Models of Melanoma. Int J Mol Sci. 2017;18: pubmed publisher..Promising results have been obtained with regard to identifying effective approved agents and experimental therapeutics, as well as combinations of the two using the melanoma PDOX model. ..