Clinical Applications of Hyaluronidase

Weber, Gregor Cornelius; Buhren, Bettina Alexandra; Schrumpf, Holger; Wohlrab, Johannes; Gerber, Peter Arne

doi:10.1007/978-981-13-7709-9_12

Cited by 73 publications

(73 citation statements)

References 162 publications

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“…24 Originally found in bacteria, hyaluronidase is widely distributed in nature and is found in many species, including insects, snakes, fish and mammals. 25 Hyaluronidase has been applied to manage lymphoedema and keloids 26,27 and is used clinically as an adjuvant to increase the bioavailability of other medications. 28 Hyaluronidase is also used for local infiltration anaesthesia, 29 extravasation management, smoothing of wrinkles and folds and management of complications associated with hyaluronidase-based filler aesthetic injections.…”

Section: Discussionmentioning

confidence: 99%

“…28 Hyaluronidase is also used for local infiltration anaesthesia, 29 extravasation management, smoothing of wrinkles and folds and management of complications associated with hyaluronidase-based filler aesthetic injections. 25 Hyaluronidase can alternatively degrate collagen in patients with submucous fibrosis and decrease collagen formation. 19 In addition, The corticosteroid combined with hyaluronidase was dexamethasone in all studies of this meta-analysis except one study, in which the steroid was hydrocortisone acetate.…”

Section: Discussionmentioning

confidence: 99%

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Efficacy of hyaluronidase combined with corticosteroids in treatment of oral submucous fibrosis: A meta‐analysis of randomized controlled clinical trials

Guo

Xie

Mao

et al. 2020

J Oral Pathology Medicine

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Objective: This meta-analysis was performed to systematically evaluate the efficacy of hyaluronidase combined with corticosteroids compared with other drugs in improving maximum mouth opening and alleviating the burning sensation in patients with oral submucous fibrosis (OSF). Methods:PubMed, Embase, Web of Science and the Cochrane Library were searched.RevMan 5.3 software was used for the meta-analysis.Results: Six studies involving 244 patients with OSF were analysed. No significant difference in improvement of maximum mouth opening was found between the hyaluronidase and control groups (lycopene, pentoxifylline, aloe vera, dexamethasone, Turmix [curcumin + piperine] and isoxsuprine) at 1 month (mean difference [MD]: 0.32, 95% confidence interval [CI]: −0.92-1.56, P = .61, I 2 = 57%), 2 months (MD: 0.49, 95% CI: −0.14-1.12, P = .12, I 2 = 41%) or 3 months (MD: 0.40, 95% CI: −1.08-1.87, P = .60, I 2 = 92%). Additionally, no statistically significant difference was found in alleviation of the burning sensation between the two groups at 1 month (MD: 0.54, 95% CI: −0.62-1.71, P = .36, I 2 = 0%), 2 months (MD: 0.53, 95% CI: −0.85-1.91, P = .45, I 2 = 0%) or 3 months (MD: 0.64, 95% CI: −1.07 to 2.35, P = .46, I 2 = 0%). Conclusions:According to this meta-analysis, weak evidence indicates that hyaluronidase combined with corticosteroids has no additional clinical benefit over control drugs (lycopene, pentoxifylline, aloe vera, dexamethasone, Turmix and isoxsuprine) in improving maximum mouth opening and alleviating the burning sensation in patients with OSF. Therefore, more high-quality, multi-centre randomized controlled trials with larger samples are needed to further assess the efficacy of hyaluronidase combined with corticosteroids in the treatment of OSF. K E Y W O R D Shyaluronidase, meta-analysis, oral submucous fibrosis

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Efficacy of hyaluronidase combined with corticosteroids in treatment of oral submucous fibrosis: A meta‐analysis of randomized controlled clinical trials

Guo

Xie

Mao

et al. 2020

J Oral Pathology Medicine

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“…To solve the problem of CAR-T's inability to in ltrate tumors effectively, we co-expressed hyaluronidase PH20 (sperm adhesion molecule 1 or SPAM 1) on the CAR-T surface. PH20 is the most active human hyaluronidase [19]. It is involved in fertilization and is expressed in the head and acrosome of human spermatozoa.…”

Section: Discussionmentioning

confidence: 99%

“…Reports suggest that recombinant hyaluronidase rHPH20 has a greater clinical effect on ECM degradation, promoting lymphocyte in ltration into tumor cells [17,18]. PH20 is a GPI-anchored membrane protein which may play a positive role in CAR-T cell treatment of solid tumors [19].…”

Section: Introductionmentioning

confidence: 99%

Co-expression of IL-7 and PH20 Promote anti-GPC3 CAR-T Tumor Suppressor Activity in Vivo and in Vitro

Liu

Wang

Jiang

et al. 2020

Preprint

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While CAR-T therapy has successfully treated hematological malignancies, it has proved sub-optimal for solid tumors. The main limitation is the inability of CAR-T cells to infiltrate and then proliferate within tumors. In this study, we co-expressed IL-7 and PH20, a type of hyaluronidase, with CAR targeting GPC3 (G3CAR-7×20) to address these issues. We found (G3CAR-7×20) exhibited better proliferation in vivo and in vitro than G3CAR, reduced the level of apoptosis after stimulation by tumor cells, and maintained the memory phenotype of CAR-T cells. G3CAR-7×20 also increased the ability of CAR-T cells to infiltrate tumor tissue. G3CAR-7×20 may significantly enhance the efficacy of CAR-T cells in solid tumors.

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“…In ophthalmological and surgical applications, HYAL is primarily employed as a so called spreading factor for cutaneous in ltration, as the addition of HYAL to in ltrating local anesthetics accelerates anesthetic diffusion and expansion of the anesthetized area (Narayanan and Kuppermann, 2009, Weber et al, 2019, Wohlrab et al, 2012. In addition to its use in local anesthesia, HYAL is used to manage complications following aesthetic injections of HA-llers.…”

Section: Introductionmentioning

confidence: 99%

Dose- and time-dependent effects of hyaluronidase on structural cells and the extracellular matrix of the skin

Buhren

Schrumpf

Gorges

et al. 2020

Preprint

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BACKGROUNDHyaluronic acid (hyaluronan; HA) is an essential component of the extracellular matrix (ECM) of the skin. The HA-degrading enzyme hyaluronidase (HYAL) is critically involved in the HA-metabolism. Yet, only little information is available regarding the skin´s HA-HYAL interactions on the molecular and cellular levels.To analyze the dose- and time-dependent molecular and cellular effects of HYAL on structural cells and the HA-metabolism in the skin.METHODSChip-based, genome-wide expression analyses (Affymetrix® GeneChip PrimeView™ Human Gene Expression Array), quantitative real-time PCR analyses, enzyme-linked immunosorbent assay (ELISA), immunohistochemistry (DAB), and in vitro wound healing assays were performed to assess dose-dependent and time-kinetic effects of HA and HYAL (bovine hyaluronidase, Hylase Dessau) on normal human dermal fibroblasts (NHDF), primary human keratinocytes in vitro and human skin samples ex vivo.RESULTSGenome-wide expression analyses revealed an upregulation of HA synthases (HAS) up to 1.8-fold change in HA- and HYAL-treated NHDF. HA and HYAL significantly accelerated wound closure in an in vitro model for cutaneous wound healing. HYAL induced HAS1 and HAS2 mRNA gene expression in NHDF. Interestingly, low concentrations of HYAL (0.015 U/ml) resulted in a significantly higher induction of HAS compared to moderate (0.15 and 1.5 U/ml) and high concentrations (15 U/ml) of HYAL. This observation corresponded to increased concentrations of HA measured by ELISA in conditioned supernatants of HYAL-treated NHDF with the highest concentrations observed for 0.015 U/ml of HYAL. Finally, immunohistochemical analysis of human skin samples incubated with HYAL for up to 48 hrs ex vivo demonstrated that low concentrations of HYAL (0.015 U/ml) led to a pronounced accumulation of HA, whereas high concentrations of HYAL (15 U/ml) reduced dermal HA-levels.CONCLUSIONSHYAL is a bioactive enzyme that exerts multiple effects on the HA-metabolism as well as on the structural cells of the skin. Our results indicate that HYAL promotes wound healing and exerts a dose-dependent induction of HA-synthesis in structural cells of the skin. Herein, interestingly the most significant induction of HAS and HA were observed for the lowest concentration of HYAL.

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Clinical Applications of Hyaluronidase

Cited by 73 publications

References 162 publications

Efficacy of hyaluronidase combined with corticosteroids in treatment of oral submucous fibrosis: A meta‐analysis of randomized controlled clinical trials

Efficacy of hyaluronidase combined with corticosteroids in treatment of oral submucous fibrosis: A meta‐analysis of randomized controlled clinical trials

Co-expression of IL-7 and PH20 Promote anti-GPC3 CAR-T Tumor Suppressor Activity in Vivo and in Vitro

Dose- and time-dependent effects of hyaluronidase on structural cells and the extracellular matrix of the skin

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