Increased expression of tissue inhibitor of metalloproteinase‐1 correlates with improved outcome in canine cutaneous mast cell tumours

Pulz, Lidia Hildebrand; Barra, Camila Neri; Kleeb, Silvia Regina; Xavier, José Guilherme; Catão‐Dias, José Luiz; Sobral, Renata Afonso; Fukumasu, Heidge; Strefezzi, Ricardo de Francisco

doi:10.1111/vco.12204

Cited by 10 publications

(13 citation statements)

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“…, Pulz et al . ). TIMPs are secreted molecules that are natural broad‐spectrum inhibitors of MMPs which also control MMP‐driven turnover and processing of growth factors as well as cytokines linked to wound repair and regeneration (Clark et al .…”

Section: Introductionmentioning

confidence: 97%

“…Tissue inhibitor of metalloproteinase 1 (TIMP1) prevents the extracellular matrix (ECM) from being decomposed by forming an inhibitory complex with matrix metalloproteinases (MMPs) (Bao et al 2014, Pulz et al 2017. TIMPs are secreted molecules that are natural broad-spectrum inhibitors of MMPs which also control MMP-driven turnover and processing of growth factors as well as cytokines linked to wound repair and regeneration (Clark et al 2008).…”

Section: Introductionmentioning

confidence: 99%

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Effect of tissue inhibitor of metalloprotease 1 on human pulp cells in vitro and rat pulp tissue in vivo

et al. 2019

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Aim To evaluate the dentinogenetic effects of tissue inhibitor of metalloprotease (TIMP1) on human pulp cells in vitro and rat pulp tissue in vivo. Methodology The effect of TIMP1 on pulp cell functions related to hard tissue formation as part of the wound healing process (i.e. biocompatibility, proliferation, differentiation and mineralized nodule formation) was evaluated in vitro and using a direct pulp capping experimental animal model in vivo. The effects of different‐sized cavity preparations on hard tissue formation induced by ProRoot MTA at 2 weeks were evaluated using micro‐computed tomography (micro‐CT). Tertiary dentine formation quality and quantity after pulp capping using TIMP1, ProRoot MTA and phosphate‐buffered saline (PBS) was also evaluated after 4 weeks using micro‐CT in term of dentine volume (DV), dentine mineral density (DVD) and histological analysis. The data were evaluated by Student's t‐test, one‐way ANOVA with Tukey's post hoc test, the Kruskal–Wallis test or the Steel–Dwass test. P values < 0.05 were considered statistically significant. Results TIMP1 significantly stimulated dental pulp stem cell proliferation, differentiation, and mineralization and was more biocompatible compared with the PBS control (P < 0.05). In the pulp capping model, the amount of tertiary dentine that formed was directly proportional to the size of the pulp exposure; greater amounts of tertiary dentine were observed in pulps with larger exposures after 2 weeks. 4‐week samples of TIMP1 and ProRoot MTA had similar characteristics, but both sample significantly induced tertiary dentine formation beneath the cavity compared with PBS (P < 0.05) under standardized cavity preparations. Conclusions TIMP1 has an important role in pulpal wound healing, which makes it a potential biological pulp capping material and candidate molecule for regenerative endodontic therapy.

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Section: Introductionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Effect of tissue inhibitor of metalloprotease 1 on human pulp cells in vitro and rat pulp tissue in vivo

et al. 2019

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“…Conversely, ECM degradation may release factors that stimulate angiogenesis, cell proliferation and migration, or inhibit apoptosis . For example, matrix metalloproteinases (MMPs) are expressed under the influence of the ECM, and facilitate invasion and metastasis via degradation of epithelial and blood vessel basement membranes . Compounds that inhibit the adhesion of cancer cells to the ECM may prevent metastasis …”

Section: Introductionmentioning

confidence: 99%

Intratumoral collagen index predicts mortality and survival in canine cutaneous mast cell tumours

Daniel

Barra

Pulz

et al. 2019

Veterinary Dermatology

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Background -Mast cell tumours (MCTs) constitute almost 25% of cutaneous neoplasms in dogs. Their biological behaviour is predicted using histopathological grading which is based on several subjective criteria that are vulnerable to intra-and interobserver variability. To improve the prediction of the biological behaviour, several complementary markers have been studied. The integrity of the extracellular matrix (ECM) may play a protective role against tumoral progression, and favour cellular proliferation, angiogenesis, invasion and metastases when altered.Hypothesis/Objectives -To evaluate the quantification of collagen and elastic fibres as prognostic markers for MCTs.Animals -Thirty-eight random cases of canine cutaneous MCT surgically treated with wide margins were included.Methods and materials -Intratumoral collagen and elastic fibres were identified and quantified on histological sections stained with Masson's trichrome, Picrosirius red and Verhoeff; the results were compared with histopathological grades, mortality due to the disease and postsurgical survival.Results -Morphometric analysis revealed a significant relationship between histopathological grade and intratumoral collagen index (CoI). In addition, the CoI was considered an independent indicator for mortality and postsurgical survival.Conclusions and clinical importance -These results support the importance of the CoI in the grading and prognosis of MCTs, suggesting that preservation and/or synthesis of collagen have the potential to become targets for MCT therapeutics.

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“…In parallel to histopathological examination, other prognostic indicators such as proliferation markers, KIT‐staining patterns and proteins related to extracellular matrix remodeling have been evaluated. Our research group has also demonstrated that low expression of BAX, one of the key factors of apoptosis, is related to longer survival …”

Section: Introductionmentioning

confidence: 99%

Apoptotic intrinsic pathway proteins predict survival in canine cutaneous mast cell tumours

Barra

Macêdo

Cadrobbi

et al. 2017

Vet Comparative Oncology

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Mast cell tumours (MCTs) are the most frequent canine round cell neoplasms and show variable biological behaviours with high metastatic and recurrence rates. The disease is treated surgically and wide margins are recommended. Adjuvant chemotherapy and radiotherapy used in this disease cause DNA damage in neoplastic cells, which is aimed to induce apoptotic cell death. Resisting cell death is a hallmark of cancer, which contributes to the development and progression of tumours. The aim of this study was to investigate the expression of the proteins involved in the apoptotic intrinsic pathway and to evaluate their potential use as prognostic markers for canine cutaneous MCTs. Immunohistochemistry for BAX, BCL2, APAF1, Caspase-9, and Caspase-3 was performed in 50 canine cases of MCTs. High BAX expression was associated with higher mortality rate and shorter survival. BCL2 and APAF1 expressions offered additional prognostic information to the histopathological grading systems. The present results indicate that variations in the expression of apoptotic proteins are related to malignancy of cutaneous MCTs in dogs.

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Increased expression of tissue inhibitor of metalloproteinase‐1 correlates with improved outcome in canine cutaneous mast cell tumours

Cited by 10 publications

References 62 publications

Effect of tissue inhibitor of metalloprotease 1 on human pulp cells in vitro and rat pulp tissue in vivo

Effect of tissue inhibitor of metalloprotease 1 on human pulp cells in vitro and rat pulp tissue in vivo

Intratumoral collagen index predicts mortality and survival in canine cutaneous mast cell tumours

Apoptotic intrinsic pathway proteins predict survival in canine cutaneous mast cell tumours

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