Keratinocyte growth factor in focus: A comprehensive review from structural and functional aspects to therapeutic applications of palifermin

Sadeghi, Sedigheh; Kalhor, Hourieh; Panahi, Mohammad Hossein; Abolhasani, Hoda; Rahimi, Bahareh; Kalhor, Reyhaneh; Mehrabi, Amirmehdi; Vahdatinia, Mahsa; Rahimi, Hamzeh

doi:10.1016/j.ijbiomac.2021.09.151

Cited by 13 publications

(13 citation statements)

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“…Oral mucositis is a severe complication during chemo‐ and/or radiation therapy. Oral mucositis can be prevented by treatment with recombinant FGF7 (Palifermin) (Raber‐Durlacher et al, 2013; Sadeghi et al, 2021).…”

Section: Therapeutic Activation Of Fgf Signaling Pathwaysmentioning

confidence: 99%

New developments in the biology of fibroblast growth factors

Ornitz

Itoh

2022

WIREs Mechanisms of Disease

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The fibroblast growth factor (FGF) family is composed of 18 secreted signaling proteins consisting of canonical FGFs and endocrine FGFs that activate four receptor tyrosine kinases (FGFRs 1-4) and four intracellular proteins (intracellular FGFs or iFGFs) that primarily function to regulate the activity of voltagegated sodium channels and other molecules. The canonical FGFs, endocrine FGFs, and iFGFs have been reviewed extensively by us and others. In this review, we briefly summarize past reviews and then focus on new developments in the FGF field since our last review in 2015. Some of the highlights in the past 6 years include the use of optogenetic tools, viral vectors, and inducible transgenes to experimentally modulate FGF signaling, the clinical use of small molecule FGFR inhibitors, an expanded understanding of endocrine FGF signaling, functions for FGF signaling in stem cell pluripotency and differentiation, roles for FGF signaling in tissue homeostasis and regeneration, a continuing elaboration of mechanisms of FGF signaling in development, and an expanding appreciation of roles for FGF signaling in neuropsychiatric diseases.

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Section: Therapeutic Activation Of Fgf Signaling Pathwaysmentioning

confidence: 99%

New developments in the biology of fibroblast growth factors

Ornitz

Itoh

2022

WIREs Mechanisms of Disease

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“…The binding of KGF to KGFR requires heparin/HS as a coreceptor. This process includes the dimerization of KGFR and activation of its kinase domain, inducing autophosphorylation of the receptor [45]. To bind to the receptor and its ligands, KGF has a positively charged site called the heparin binding site, and a neutral site that binds to KGFR.…”

Section: Kgfmentioning

confidence: 99%

“…For example, KGF has poor in vivo bioactivity. KGF has a short biological half-life and poor stability, its biological activity is susceptible to environmental factors, and it cannot maintain bioactivity for a long time in the presence of other enzymes [45].…”

Section: Future Prospects For Amscmp For Tissue Engineeringmentioning

confidence: 99%

Prospective use of amniotic mesenchymal stem cell metabolite products for tissue regeneration

Miatmoko

Hariawan²,

Cahyani³

et al. 2023

J Biol Eng

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Chronic disease can cause tissue and organ damage constituting the largest obstacle to therapy which, in turn, reduces patients’ quality-adjusted life-year. Degenerative diseases such as osteoporosis, Alzheimer’s disease, Parkinson’s disease, and infectious conditions such as hepatitis, cause physical injury to organs. Moreover, damage resulting from chronic conditions such as diabetes can also culminate in the loss of organ function. In these cases, organ transplantation constitutes the therapy of choice, despite the associated problems of immunological rejection, potential disease transmission, and high morbidity rates. Tissue regeneration has the potential to heal or replace tissues and organs damaged by age, disease, or trauma, as well as to treat disabilities. Stem cell use represents an unprecedented strategy for these therapies. However, product availability and mass production remain challenges. A novel therapeutic alternative involving amniotic mesenchymal stem cell metabolite products (AMSC-MP) has been developed using metabolites from stem cells which contain cytokines and growth factors. Its potential role in regenerative therapy has recently been explored, enabling broad pharmacological applications including various gastrointestinal, lung, bladder and renal conditions, as well as the treatment of bone wounds, regeneration and skin aging due to its low immunogenicity and anti-inflammatory effects. The various kinds of growth factors present in AMSC-MP, namely bFGF, VEGF, TGF-β, EGF and KGF, have their respective functions and activities. Each growth factor is formed by different proteins resulting in molecules with various physicochemical properties and levels of stability. This knowledge will assist in the manufacture and application of AMSC-MP as a therapeutic agent.

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“…Palifermin (Kepivance) is a recombinant human keratinocyte growth factor (KGF) that stimulates epithelial cell proliferation (via activation of the Raf/MAPK/ERK pathway and decreasing expression of checkpoint suppressor-1), differentiation (via activation of various mitogenic genes such as cyclin G, cyclin D, and E2F1 pRB binding protein gene), migration (via activation of Src-Cortactin and activation of cell motility pathways), and survival (via activation of the antiapoptotic-Akt-dependent pathway). 31,32 Palifermin has been approved by the FDA as a radioprotectant in patients undergoing total body irradiation for hematopoietic stem cell transplants (HSCTs). 33,34 In head and neck patients, palifermin may ameliorate and prevent oral mucositis; a multicenter double-blind RCT of palifermin versus placebo showed that 51% of patients with palifermin developed severe mucositis versus 67% with placebo.…”

Section: Paliferminmentioning

confidence: 99%

“…As KGF receptors are ubiquitous in the human body, and differential KGF expression has been implicated in various disease processes, such as autosomal dominant polycystic kidney disease, long-term safety is a concern for palifermin as it may have tumorigenic potential. [32][33][34] Furthermore, palifermin is expensive, and pharmacoeconomic studies in HSCT patients found equivocal evidence whether the clinical benefit offsets the financial cost. 37,38 Hyperbaric Oxygen Therapy Hyperbaric oxygen therapy (HBOT) has been used as a woundhealing adjunct for decades.…”

Section: Paliferminmentioning

confidence: 99%

Noninvasive Systemic Modalities for Prevention of Head and Neck Radiation-Associated Soft Tissue Injury: A Narrative Review

Kim

Rubenstein

Chu

et al. 2022

J Reconstr Microsurg

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Background Radiation-associated soft tissue injury is a potentially devastating complication for head and neck cancer patients. The damage can range from minor sequelae such as xerostomia, which requires frequent daily maintenance, to destructive degenerative processes such as osteoradionecrosis, which can contribute to flap failure and delay or reverse oral rehabilitation. Despite the need for effective radioprotectants, the literature remains sparse, primarily focused on interventions beyond the surgeon's control, such as maintenance of good oral hygiene or modulation of radiation dose. Methods This narrative review aggregates and explores noninvasive, systemic treatment modalities for prevention or amelioration of radiation-associated soft tissue injury. Results We highlighted nine modalities with the most clinical potential, which include amifostine, melatonin, palifermin, hyperbaric oxygen therapy, photobiomodulation, pentoxifylline–tocopherol–clodronate, pravastatin, transforming growth factor-β modulators, and deferoxamine, and reviewed the benefits and limitations of each modality. Unfortunately, none of these modalities are supported by strong evidence for prophylaxis against radiation-associated soft tissue injury. Conclusion While we cannot endorse any of these nine modalities for immediate clinical use, they may prove fruitful areas for further investigation.

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Keratinocyte growth factor in focus: A comprehensive review from structural and functional aspects to therapeutic applications of palifermin

Cited by 13 publications

References 100 publications

New developments in the biology of fibroblast growth factors

New developments in the biology of fibroblast growth factors

Prospective use of amniotic mesenchymal stem cell metabolite products for tissue regeneration

Noninvasive Systemic Modalities for Prevention of Head and Neck Radiation-Associated Soft Tissue Injury: A Narrative Review

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