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https://read.qxmd.com/read/30867142/olaratumab-combined-with-doxorubicin-and-ifosfamide-overcomes-individual-doxorubicin-and-olaratumab-resistance-of-an-undifferentiated-soft-tissue-sarcoma-in-a-pdox-mouse-model
#1
Takashi Higuchi, Kentaro Miyake, Norihiko Sugisawa, Hiromichi Oshiro, Zhiying Zhang, Sahar Razmjooei, Norio Yamamoto, Katsuhiro Hayashi, Hiroaki Kimura, Shinji Miwa, Kentaro Igarashi, Michael Bouvet, Shree Ram Singh, Hiroyuki Tsuchiya, Robert M Hoffman
Olaratumab (OLA), a monoclonal antibody against platelet-derived growth factor receptor alpha (PDGFRα), has recently been used against soft-tissue sarcoma (STS) combined with doxorubicin (DOX), with limited efficacy. The goal of present study was to determine the efficacy of OLA in combined with doxorubicin (DOX) and ifosfamide (IFO) on STS. Undifferentiated soft-tissue sarcoma (USTS) from a striated muscle of a patient was grown orthotopically in the right biceps femoris muscle of nude mice to establish an undifferentiated soft-tissue sarcoma (USTS) patient-derived orthotopic xenograft (PDOX) model...
March 10, 2019: Cancer Letters
https://read.qxmd.com/read/30807865/a-patient-derived-orthotopic-xenograft-pdox-nude-mouse-model-precisely-identifies-effective-and-ineffective-therapies-for-recurrent-leiomyosarcoma
#2
Zhiying Zhang, Kaiwen Hu, Tasuko Kiyuna, Kentaro Miyake, Kei Kawaguchi, Kentaro Igarashi, Scott D Nelson, Yunfeng Li, Shree Ram Singh, Robert M Hoffman
Leiomyosarcoma is a rare and recalcitrant disease. Doxorubicin (DOX) is usually considered first-line treatment for this disease, but frequently is ineffective. In order to individualize therapy for this and other cancers, we have developed the patient-derived orthotopic xenograft (PDOX) mouse model. In the present study, we implanted a recurrent leiomyosarcoma from a resected tumor from the patient's thigh into the femoral muscle of nude mice. The following drugs were tested on the leiomyosarcoma PDOX model: DOX, the combination of gemcitabine (GEM) and docetaxel (DOC), trabectedin (TRA), temozolomide (TEM), pazopanib (PAZ) and olaratumab (OLA)...
February 23, 2019: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://read.qxmd.com/read/30765319/serial-patient-derived-orthotopic-xenografting-of-adenoid-cystic-carcinomas-recapitulates-stable-expression-of-phenotypic-alterations-and-innervation
#3
Ashley Cornett, Harleen K Athwal, Emily Hill, George Murphy, Kenji Yeoh, Christopher A Moskaluk, Robert L Witt, Nisha J D'Silva, Seema Agarwal, Isabelle M A Lombaert
BACKGROUND: Patient-derived xenograft (PDX) models have significantly enhanced cancer research, and often serve as a robust model. However, enhanced growth rate and altered pathological phenotype with serial passages have repeatedly been shown in adenoid cystic carcinoma (ACC) PDX tumors, which is a major concern. METHODS: We evaluated the fidelity of ACCs in their natural habitat by performing ACC orthotopic xenotransplantation (PDOX) in salivary glands. FINDINGS: Our PDOX model enabled solid tumors to integrate within the local epithelial, stromal and neuronal environment...
February 11, 2019: EBioMedicine
https://read.qxmd.com/read/30762861/correction-au-pdo-x-with-a-pdo-x-rich-shell-and-au-rich-core-embedded-in-co-3-o-4-nanorods-for-catalytic-combustion-of-methane
#4
Nating Yang, Jingwei Liu, Yuhan Sun, Yan Zhu
Correction for 'Au@PdOx with a PdOx-rich shell and Au-rich core embedded in Co3O4 nanorods for catalytic combustion of methane' by Yan Zhu et al., Nanoscale, 2017, 9, 2123-2128.
February 14, 2019: Nanoscale
https://read.qxmd.com/read/30758647/regorafenib-regressed-a-doxorubicin-resistant-ewing-s-sarcoma-in-a-patient-derived-orthotopic-xenograft-pdox-nude-mouse-model
#5
Kentaro Miyake, Tasuku Kiyuna, Kei Kawaguchi, Takashi Higuchi, Hiromichi Oshiro, Zhiying Zhang, Sintawat Wangsiricharoen, Sahar Razmjooei, Yunfeng Li, Scott D Nelson, Takashi Murakami, Yukihiko Hiroshima, Ryusei Matsuyama, Michael Bouvet, Sant P Chawla, Shree Ram Singh, Itaru Endo, Robert M Hoffman
PURPOSE: Ewing's sarcoma (ES) is a rare and recalcitrant disease which is in need of a development of a novel effective therapy. The aim of this study was to investigate the efficacy of regorafenib on an ES tumor in a patient-derived orthotopic xenograft (PDOX) model. METHODS: The ES PDOX models were established orthotopically in the right chest wall of nude mice to match the site of the tumor in the donor patient. The ES PDOX models were randomized into three groups (G) when the tumor volume reached 75 mm3 : G1: untreated control; G2: doxorubicin (DOX) (i...
February 13, 2019: Cancer Chemotherapy and Pharmacology
https://read.qxmd.com/read/30725426/afterword-oral-methioninase-answer-to-cancer-and-fountain-of-youth
#6
Robert M Hoffman, Qinghong Han, Kei Kawaguchi, Shukuan Li, Yuying Tan
The elevated methionine (MET) requirement of cancer cells is termed MET dependence and is possibly the only known general metabolic defect in cancer. Targeting MET by recombinant methioninase (rMETase) can arrest the growth of cancer cells in vitro and in vivo due to their elevated requirement for MET. rMETase can also potentiate chemotherapy drugs active in S phase due to the selective arrest of cancer cells in S/G2 phase during MET restriction (MR). We previously reported that rMETase, administrated by intraperitoneal injection (ip-rMETase), could inhibit tumor growth in mouse models of cancer including patient-derived orthotopic xenograft (PDOX) mouse models...
2019: Methods in Molecular Biology
https://read.qxmd.com/read/30725414/high-efficacy-of-recombinant-methioninase-on-patient-derived-orthotopic-xenograft-pdox-mouse-models-of-cancer
#7
Robert M Hoffman, Takashi Murakami, Kei Kawaguchi, Kentaro Igarashi, Yuying Tan, Shukuan Li, Qinghong Han
Methionine (MET) is a general target in cancer due to the excess requirement of MET by cancer cells. MET has been effectively restricted by recombinant methioninase (rMETase) in mouse models of cell-line tumors. This chapter reviews the efficacy of rMETase on patient-derived orthotopic xenograft (PDOX) mouse models of human cancer. Ewing's sarcoma is a recalcitrant disease even though development of multimodal therapy has improved patients' outcome. A Ewing's sarcoma was implanted in the right chest wall of nude mice to establish a PDOX model...
2019: Methods in Molecular Biology
https://read.qxmd.com/read/30725413/methioninase-cell-cycle-trap-cancer-chemotherapy
#8
Robert M Hoffman, Shuya Yano, Kentaro Igarashi
Cancer cells are methionine (MET) dependent compared to normal cells as they have an elevated requirement for MET in order to proliferate. MET restriction selectively traps cancer cells in the S/G2 phase of the cell cycle. The cell cycle phase can be visualized by color coding with the fluorescence ubiquitination-based cell cycle indicator (FUCCI). Recombinant methioninase (rMETase) is an enzyme that effectively degrades MET. rMETase induces S/G2 -phase blockage of cancer cells which is identified by the cancer cells' green fluorescence with FUCCI imaging...
2019: Methods in Molecular Biology
https://read.qxmd.com/read/30673664/combining-tumor-selective-bacterial-therapy-with-salmonella-typhimurium-a1-r-and-cancer-metabolism-targeting-with-oral-recombinant-methioninase-regressed-an-ewing-s-sarcoma-in-a-patient-derived-orthotopic-xenograft-model
#9
Kentaro Miyake, Tasuku Kiyuna, Shukuan Li, Qinghong Han, Yuying Tan, Ming Zhao, Hiromichi Oshiro, Kei Kawaguchi, Takashi Higuchi, Zhiying Zhang, Sahar Razmjooei, Maryam Barangi, Sintawat Wangsiricharoen, Takashi Murakami, Arun S Singh, Yunfeng Li, Scott D Nelson, Fritz C Eilber, Michael Bouvet, Yukihiko Hiroshima, Takashi Chishima, Ryusei Matsuyama, Shree Ram Singh, Itaru Endo, Robert M Hoffman
BACKGROUND: Ewing's sarcoma (ES) is a recalcitrant disease in need of transformative therapeutics. OBJECTIVES: The aim of this study was to investigate the efficacy of tumor-selective Salmonella typhimurium A1-R combined with tumor metabolism targeting with oral administration of recombinant methioninase (o-rMETase), on an ES patient-derived orthotopic xenograft (PDOX) model. METHODS: The ES PDOX models were previously established in the right chest wall...
January 23, 2019: Chemotherapy
https://read.qxmd.com/read/30660363/gemcitabine-combined-with-docetaxel-precisely-regressed-a-recurrent-leiomyosarcoma-peritoneal-metastasis-in-a-patient-derived-orthotopic-xenograft-pdox-model
#10
Kentaro Miyake, Tasuku Kiyuna, Masuyo Miyake, Kei Kawaguchi, Zhiying Zhang, Sintawat Wangsiricharoen, Sahar Razmjooei, Hiromichi Oshiro, Takashi Higuchi, Yunfeng Li, Scott D Nelson, Takashi Murakami, Yukihiko Hiroshima, Takafumi Kumamoto, Ryusei Matsuyama, Michael Bouvet, Shree Ram Singh, Sant P Chawla, Itaru Endo, Robert M Hoffman
There are no effective treatments for leiomyosarcoma (LMS) spreading intraabdominally. The aim of this study was to develop precision chemotherapy for recurrent peritoneal LMS metastases in a patient-derived orthotopic xenograft (PDOX) model. The LMS PDOX models were established orthotopically on the dome of the bladder of nude mice. The LMS PDOX models were randomized into 6 groups when the tumor volume reached 80 mm3 : G1: untreated control; G2: doxorubicin (DOX) (DOX: i.p., 3 mg/kg, weekly, 3 weeks); G3: DOX combined with olaratumab (OLA) (DOX: i...
January 16, 2019: Biochemical and Biophysical Research Communications
https://read.qxmd.com/read/30647873/fluorescent-humanized-anti-cea-antibody-specifically-labels-metastatic-pancreatic-cancer-in-a-patient-derived-orthotopic-xenograft-pdox-mouse-model
#11
Thinzar M Lwin, Kentaro Miyake, Takashi Murakami, Jonathan C DeLong, Siamak Amirfakhri, Filemoni Filemoni, Sang Nam Yoon, Paul J Yazaki, John E Shivley, Brian Datnow, Bryan M Clary, Robert M Hoffman, Michael Bouvet
Pancreatic cancer is a highly lethal disease in part due to incomplete tumor resection. Targeting by tumor-specific antibodies conjugated with a fluorescent label can result in selective labeling of cancer in vivo for surgical navigation. In the present study, we describe a patient-derived orthotopic xenograft model of pancreatic cancer that recapitulated the disease on a gross and microscopic level, along with physiologic clinical manifestations. We additionally show that the use of an anti-CEA antibody conjugated to the near-infrared (NIR) fluorescent dye, IRDye800CW, can selectively highlight the pancreatic cancer and its metastases in this model with a tumor-to-background ratio of 3...
December 18, 2018: Oncotarget
https://read.qxmd.com/read/30616082/the-combination-of-gemcitabine-and-nab-paclitaxel-as-a-novel-effective-treatment-strategy-for-undifferentiated-soft-tissue-sarcoma-in-a-patient-derived-orthotopic-xenograft-pdox-nude-mouse-model
#12
Takashi Higuchi, Kei Kawaguchi, Kentaro Miyake, Hiromichi Oshiro, Zhiying Zhang, Sahar Razmjooei, Sintawat Wangsiricharoen, Kentaro Igarashi, Norio Yamamoto, Katsuhiro Hayashi, Hiroaki Kimura, Shinji Miwa, Scott D Nelson, Sarah M Dry, Yunfeng Li, Sant P Chawla, Frederick C Eilber, Shree Ram Singh, Hiroyuki Tsuchiya, Robert M Hoffman
Undifferentiated/unclassified soft-tissue sarcomas (USTS) is recalcitrant neoplasms that is usually treated with doxorubicin (DOX)-containing regimens as first-line therapy. Nanoparticle albumin-bound paclitaxel (nab-PTX) is a nanotechnology-based drug and is widely used in pancreatic cancer in combination with gemcitabine (GEM). The major goal of the present study was to determine the efficacy of nab-PTX in combination with GEM, compared to conventional drugs such as docetaxel (DOC), GEM combined with DOC, or first-line drug DOX on a USTS not-otherwise specified (USTS/NOS) from a striated muscle implanted in the right biceps femoris muscle of nude mice to establish a patient-derived orthotopic xenograft (PDOX) model...
January 4, 2019: Biomedicine & Pharmacotherapy
https://read.qxmd.com/read/30591443/detection-of-metastasis-in-a-patient-derived-orthotopic-xenograft-pdox-model-of-undifferentiated-pleomorphic-sarcoma-with-red-fluorescent-protein
#13
Hiromichi Oshiro, Tasuku Kiyuna, Yasunori Tome, Kentaro Miyake, Kei Kawaguchi, Takashi Higuchi, Masuyo Miyake, Zhiying Zhang, Sahar Razmjooei, Maryam Barangi, Sintawat Wangsiricharoen, Scott D Nelson, Yunfeng Li, Michael Bouvet, Shree Ram Singh, Fuminori Kanaya, Robert M Hoffman
BACKGROUND/AIM: Undifferentiated pleomorphic sarcoma (UPS) is a common soft tissue sarcoma and highly recalcitrant. We have previously developed patient-derived orthotopic xenograft (PDOX) mouse models of UPS and other major sarcoma types. Unlike PDOX models of other cancer types, it has been difficult to demonstrate metastasis in the sarcoma PDOX models. MATERIALS AND METHODS: To visualize metastasis at high resolution in the UPS PDOX model, established tumor fragments were implanted in transgenic nude mice expressing red fluorescent protein (RFP) for one passage...
January 2019: Anticancer Research
https://read.qxmd.com/read/30559167/human-breast-cancer-xenograft-model-implicates-peroxisome-proliferator-activated-receptor-signaling-as-driver-of-cancer-induced-muscle-fatigue
#14
Hannah E Wilson, Kacey K Rhodes, Daniel Rodriguez, Ikttesh Chahal, David A Stanton, Joseph Bohlen, Mary Davis, Aniello M Infante, Hannah Hazard-Jenkins, David J Klinke, Elena N Pugacheva, Emidio E Pistilli
PURPOSE: This study tested the hypothesis that a patient-derived orthotopic xenograft (PDOX) model would recapitulate the common clinical phenomenon of breast cancer (BC)-induced skeletal muscle (SkM) fatigue in the absence of muscle wasting. This study additionally sought to identify drivers of this condition to facilitate the development of therapeutic agents for BC patients experiencing muscle fatigue. EXPERIMENTAL DESIGN: Eight female BC-PDOX-bearing mice were produced via transplantation of tumor tissue from eight female BC patients...
December 17, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://read.qxmd.com/read/30502564/primary-cns-lymphoma-patient-derived-orthotopic-xenograft-model-capture-the-biological-and-molecular-characteristics-of-the-disease
#15
Frédéric Pouzoulet, Agusti Alentorn, Louis Royer-Perron, Franck Assayag, Karima Mokhtari, Dalila Labiod, Magali Le Garff-Tavernier, Mailys Daniau, Emmanuelle Menet, Matthieu Peyre, Anne Schnitzler, Justine Guegan, Frédéric Davi, Khê Hoang-Xuan, Carole Soussain
Primary CNS lymphomas (PCNSL) are rare and poor prognosis diffuse large B-cell lymphomas. Because of the brain tumor environment and the restricted distribution of drugs in the CNS, specific PCNSL patient-derived orthotopic xenograft (PDOX) models are needed for preclinical research to improve the prognosis of PCNSL patients. PCNSL patient specimens (n = 6) were grafted in the caudate nucleus of immunodeficient nude mice with a 83% rate of success, while subcutaneous implantation in nude mice of human PCNSL sample did not generate lymphoma, supporting the role of the brain microenvironment in the PCNSL physiopathology...
November 16, 2018: Blood Cells, Molecules & Diseases
https://read.qxmd.com/read/30389699/measurement-of-plasma-cell-free-mitochondrial-tumor-dna-improves-detection-of-glioblastoma-in-patient-derived-orthotopic-xenograft-models
#16
Richard Mair, Florent Mouliere, Christopher G Smith, Dineika Chandrananda, Davina Gale, Francesco Marass, Dana W Y Tsui, Charles E Massie, Alan J Wright, Colin Watts, Nitzan Rosenfeld, Kevin M Brindle
The factors responsible for the low detection rate of cell-free tumor DNA (ctDNA) in the plasma of glioblastoma (GB) patients are currently unknown. In this study, we measured circulating nucleic acids in patient-derived orthotopically implanted xenograft (PDOX) models of GB (n=64) and show that tumor size and cell proliferation, but not the integrity of the blood-brain barrier or cell death, affect the release of ctDNA in treatment naïve GB PDOX. Analysis of fragment length profiles by shallow genome-wide sequencing (<0...
November 2, 2018: Cancer Research
https://read.qxmd.com/read/30366006/preclinical-modeling-of-image-guided-craniospinal-irradiation-for-very-high-risk-medulloblastoma
#17
Stephanie M C Smith, Brandon M Bianski, Brent A Orr, Gretchen Harknett, Arzu Onar-Thomas, Richard J Gilbertson, Thomas E Merchant, Martine F Roussel, Christopher L Tinkle
PURPOSE: Craniospinal irradiation (CSI) is a crucial component of treatment for medulloblastoma (MB), a brain tumor clinically stratified into prognostically distinct molecular subgroups. Preclinical models of clinically relevant CSI offer the potential to study radiation dose and volume effects in these subgroups and to identify subgroup-specific combination adjuvant therapies, particularly for very-high-risk MB in which treatments are often unsuccessful. METHODS AND MATERIALS: The commercially available Small Animal Radiation Research Platform equipped with a motorized variable collimator was used for image-guided CSI...
March 1, 2019: International Journal of Radiation Oncology, Biology, Physics
https://read.qxmd.com/read/30362476/acid-active-supramolecular-anticancer-nanoparticles-based-on-cyclodextrin-polyrotaxanes-damaging-both-mitochondria-and-nuclei-of-tumor-cells
#18
Shuang Bai, Xiaoli Zhang, Xiaoqian Ma, Jiucun Chen, Qiubing Chen, Xiaoxiao Shi, Meili Hou, Peng Xue, Yuejun Kang, Zhigang Xu
As a supramolecular macrocyclic polymer, cyclodextrin (CD) polyrotaxanes (PRs) have many advantages for developing nanomedicines, such as stable chemical composition, abundant functionalized hydroxyl groups, moving across biological barriers, adjustable nanoparticle size and good biocompatibility. Herein, we synthesized a class of acid-active therapeutic nanoparticles comprising a α-CD-based PR polymeric prodrug of PRs-poly(doxorubicin)-co-poly[(ethylene glycol) methyl ether methacrylate] (PR-PDOX-co-POEGMA, denoted as PRMO@DOX) to reduce drug leakage and selectively deliver drugs into tumor cells, aiming to achieve maximal treatment efficacy of supramolecular therapeutics...
November 20, 2018: Biomaterials Science
https://read.qxmd.com/read/30309504/tumor-targeting-salmonella-typhimurium-a1-r-overcomes-partial-carboplatinum-resistance-of-a-cancer-of-unknown-primary-cup
#19
Kentaro Miyake, Tasuku Kiyuna, Masuyo Miyake, Ming Zhao, Sintawat Wangsiricharoen, Kei Kawaguchi, Zhiying Zhang, Takashi Higuchi, Sahar Razmjooei, Yunfeng Li, Scott D Nelson, Tara Russell, Arun Singh, Takashi Murakami, Yukihiko Hiroshima, Masashi Momiyama, Ryusei Matsuyama, Takashi Chishima, Shree Ram Singh, Sant P Chawla, Fritz C Eilber, Itaru Endo, Robert M Hoffman
Cancer of unknown primary (CUP) is metastatic disease without a known primary and therefore very difficult to identify effective therapy. Previously, we demonstrated partial efficacy of Salmonella typhimurium A1-R (S. typhimurium A1-R) alone and carboplatinum alone (CAR) on a CUP patient tumor in the patient-derived xenograft (PDOX) model. The aim of the present study was to investigate the efficacy of S. typhimurium A1-R combined with CAR on the CUP PDOX model. The CUP tumors were implanted orthotopically into the left supraclavicular fossa of nude mice to match the site from which they were resected from the patient...
October 2018: Tissue & Cell
https://read.qxmd.com/read/30292411/a-combination-of-irinotecan-cisplatinum-and-irinotecan-temozolomide-or-tumor-targeting-salmonella-typhimurium-a1-r-arrest-doxorubicin-and-temozolomide-resistant-myxofibrosarcoma-in-a-pdox-mouse-model
#20
Tasuku Kiyuna, Yasunori Tome, Takashi Murakami, Kentaro Miyake, Kentaro Igarashi, Kei Kawaguchi, Hiromichi Oshiro, Takashi Higuchi, Masuyo Miyake, Norihiko Sugisawa, Zhiying Zhang, Sahar Razmjooei, Sintawat Wangsiricharoen, Bartosz Chmielowski, Scott D Nelson, Tara A Russell, Sarah M Dry, Yunfeng Li, Mark A Eckardt, Arun S Singh, Sant Chawla, Fuminori Kanaya, Fritz C Eilber, Shree Ram Singh, Ming Zhao, Robert M Hoffman
Myxofibrosarcoma (MFS) is the most common sarcomas in elderly patients and is either chemo-resistant or recurs with metastasis after chemotherapy. This recalcitrant cancer in need of improved treatment. We have established a patient-derived orthotopic xenograft (PDOX) of MFS. The MFS PDOX model was established in the biceps femoris of nude mice and randomized into 7 groups of 7 mice each: control; doxorubicin (DOX); pazopanib (PAZ); temozolomide (TEM); Irinotecan (IRN); IRN combined with TEM; IRN combined with cisplatinum (CDDP) and Salmonella typhimurium A1-R (S...
November 2, 2018: Biochemical and Biophysical Research Communications
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