Therapeutic Intervention Using a Smad7-Based Tat Protein to Treat Radiation-Induced Oral Mucositis

Boss, Mary‐Keara; Ke, Yao; Bian, Li; Lee, Ber‐In; Prebble, Amber; Martin, Tiffany; Trageser, Erin; Hall, Spencer; Wang, Donna D.; Wang, Suyan; Chow, Lyndah; Holwerda, Barry; Raben, David; Regan, Daniel; Karam, Sana D.; Dow, Steven; Young, Christian D.; Wang, Xiaojing

doi:10.1016/j.ijrobp.2021.09.039

Cited by 8 publications

(5 citation statements)

References 22 publications

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“…Prior to analysis by NanoString, RNA quality and quantity were assessed by NanoDrop spectrophotometry and integrity evaluated by Agilent TapeStation. All RNA samples analyzed contained RNA molecules in size >200 nucleotides or larger exceeding 50% of total RNA ( 66 ). Analysis of transcript abundance and statistical significance was performed with the nCounter Analysis Flex software and with Partek ® Flow ® Genomics Analysis software v10.0 (Partek Inc., Chesterfield, MO, USA).…”

Section: Methodsmentioning

confidence: 99%

Erythrocyte removal from bone marrow aspirate concentrate improves efficacy as intra-articular cellular therapy in a rodent osteoarthritis model

Pezzanite¹,

Timkovich²,

Sikes³

et al. 2023

Ann Transl Med

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Background Despite the high prevalence of osteoarthritis (OA), there remains a need for additional therapeutic options. Cellular therapies with minimally manipulated cells such as bone marrow aspirate concentrates (BMAC) are increasingly popular in the U.S. but clear-cut evidence of efficacy has not been established. In theory, BMAC injections provide a source of stromal cells to stimulate healing in OA and ligamentous injuries; however, BMAC injections are also often associated with inflammation, short-term pain, and mobility impairment. Given that blood is known to trigger inflammation in joints, we hypothesized that removing erythrocytes [red blood cells (RBCs)] from BMAC preparations prior to intra-articular injection would improve efficacy for OA treatment. Methods To test this hypothesis, BMAC was collected from the bone marrow of mice. Three treatment groups were pursued: (I) untreated; (II) BMAC; or (III) BMAC depleted of RBCs by lysis. Product was injected into the femorotibial joint of mice 7 days after OA had been induced by destabilization of the medial meniscus (DMM). To assess the impact of treatment on joint function, individual cage monitoring (ANY-maze TM ) and Digigait treadmill-based analyses were performed over 4 weeks. At study completion, joint histopathology was assessed and immune transcriptomes within joint tissues were compared using a species-specific NanoString panel. Results Significant improvements in activity, gait parameters, and histology scores were seen in animals receiving RBC-depleted BMAC compared to untreated mice; animals treated with non-depleted BMAC did not demonstrate this same extent of consistent significant improvement. Transcriptomic analysis of joint tissues revealed significant upregulation of key anti-inflammatory genes, including interleukin-1 receptor antagonist (IRAP), in mice treated with RBC-depleted BMAC compared to animals treated with non-RBC depleted BMAC. Conclusions These findings indicate that RBC depletion in BMAC prior to intra-articular injection improves treatment efficacy and reduces joint inflammation compared to BMAC.

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Section: Methodsmentioning

confidence: 99%

Erythrocyte removal from bone marrow aspirate concentrate improves efficacy as intra-articular cellular therapy in a rodent osteoarthritis model

Pezzanite¹,

Timkovich²,

Sikes³

et al. 2023

Ann Transl Med

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“…More recently, high intensity focused ultrasound (HIFU) was used to treat pet dogs with solid tumours and nCounter analysis of biopsy samples demonstrated differential expression of 28 genes associated with T‐cell activation following treatment 103 . Several other groups have published gene expression data generated from canine samples using the nCounter platform, and a multitude of studies are ongoing using this tool as part of the PRECINCT consortium 104–106 . It is worth noting that custom panels can be designed to facilitate targeted interrogation.…”

Section: Emerging Technologies and Resourcesmentioning

confidence: 99%

“…103 Several other groups have published gene expression data generated from canine samples using the nCounter platform, and a multitude of studies are ongoing using this tool as part of the PRECINCT consortium. [104][105][106] It is worth noting that custom panels can be designed to facilitate targeted interrogation. This approach was recently employed to support validation of an antibody panel designed to distinguish lymphoid versus myeloid lineage leukaemias, demonstrating 100% concordance between flow cytometry and gene expression for the lymphoid leukaemias and 80% concordance for myeloid leukaemias.…”

Section: Spatial Transcriptomicsmentioning

confidence: 99%

Leading the pack: Best practices in comparative canine cancer genomics to inform human oncology

London,

Gardner,

Zhao

et al. 2023

Vet Comparative Oncology

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Pet dogs develop spontaneous cancers at a rate estimated to be five times higher than that of humans, providing a unique opportunity to study disease biology and evaluate novel therapeutic strategies in a model system that possesses an intact immune system and mirrors key aspects of human cancer biology. Despite decades of interest, effective utilization of pet dog cancers has been hindered by a limited repertoire of necessary cellular and molecular reagents for both in vitro and in vivo studies, as well as a dearth of information regarding the genomic landscape of these cancers. Recently, many of these critical gaps have been addressed through the generation of a highly annotated canine reference genome, the creation of several tools necessary for multi‐omic analysis of canine tumours, and the development of a centralized repository for key genomic and associated clinical information from canine cancer patients, the Integrated Canine Data Commons. Together, these advances have catalysed multidisciplinary efforts designed to integrate the study of pet dog cancers more effectively into the translational continuum, with the ultimate goal of improving human outcomes. The current review summarizes this recent progress and provides a guide to resources and tools available for comparative study of pet dog cancers.

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“…Canine patients treated for nasal tumors with intensity-modulated radiation therapy (IMRT) have been treated with another potential radioprotectant—topical Smad7. This product reduced the severity and duration of grade 3 oral mucositis, as indicated by a lower inflammatory profile (interleukin (IL)-1β, transforming growth factor (TGF)-β, and tumor necrosis factor (TNF)-α) in canine patients [ 27 ].…”

Section: Contribution Of Small Animal Companions As a Preclinical Res...mentioning

confidence: 99%

Companion Animals as a Key to Success for Translating Radiation Therapy Research into the Clinic

Vanhaezebrouck

Scarpelli

2023

Cancers

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Many successful preclinical findings fail to be replicated during translation to human studies. This leads to significant resources being spent on large clinical trials, and in some cases, promising therapeutics not being pursued due to the high costs of clinical translation. These translational failures emphasize the need for improved preclinical models of human cancer so that there is a higher probability of successful clinical translation. Companion-animal cancers offer a potential solution. These cancers are more similar to human cancer than other preclinical models, with a natural evolution over time, genetic alterations, intact immune system, and a permanent adaptation to the microenvironment. These advantages have led pioneers in veterinary radiation oncology to aid human medicine by elucidating basic principles of radiation biology. More recently, the veterinary and human radiation oncology fields have increasingly collaborated to achieve advancements in education, radiotherapy techniques, and trial networks. This review describes these advancements, including significant prior research findings and the evolution of the veterinary radiation oncology discipline. It concludes by describing how companion-animal models can help shape the future of human radiotherapy. Taken as a whole, this review suggests companion-animal cancers may become widely used for preclinical radiotherapy research.

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Therapeutic Intervention Using a Smad7-Based Tat Protein to Treat Radiation-Induced Oral Mucositis

Cited by 8 publications

References 22 publications

Erythrocyte removal from bone marrow aspirate concentrate improves efficacy as intra-articular cellular therapy in a rodent osteoarthritis model

Erythrocyte removal from bone marrow aspirate concentrate improves efficacy as intra-articular cellular therapy in a rodent osteoarthritis model

Leading the pack: Best practices in comparative canine cancer genomics to inform human oncology

Companion Animals as a Key to Success for Translating Radiation Therapy Research into the Clinic

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