An evaluation of masitinib for treating systemic mastocytosis

Laforgia, Mariarita; Marech, Ilaria; Nardulli, Patrizia; Calabrò, Concetta; Gadaleta, Cosmo Damiano; Ranieri, Girolamo

doi:10.1080/14656566.2019.1645121

Cited by 13 publications

(15 citation statements)

References 71 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…65,66 It should also be borne in mind that plasma half-life in dogs after single administration is about 5 h and gender-dependent, leading to a two-fold higher exposure in female dogs. 66,67 Considering that the pharmacokinetics of masitinib after oral intake is not linear, administering it twice daily may lower the risk of an increased systemic exposure with associated adverse effects. 26,67,68 Such treatment adaptation is already used in human clinical trials, thus encouraging a re-evaluation of the current treatment scheme in dogs.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the therapeutic potential of masitinib and expression of its specific targets c‐Kit, PDGFR‐α, PDGFR‐β, and Lyn in canine prostate cancer cell lines

Klose

Packeiser

Granados-Soler

et al. 2022

Vet Comparative Oncology

View full text Add to dashboard Cite

Canine prostate cancer is classified into adenocarcinoma, transitional cell carcinoma with prostatic involvement, and mixed forms. Early metastatic spread leads to poor prognosis and limited treatment options. Masitinib is approved for the treatment of canine mast cell tumours and inhibits tyrosine kinase c‐Kit, tyrosine‐protein kinase Lyn (Lyn), and platelet‐derived growth factor receptors alpha and beta (PDGFR‐α, PDGFR‐β), which are known to be expressed in canine prostate cancer. The aim of this study was to evaluate masitinib in an in vitro model consisting of cell lines from primary prostate adenocarcinoma, the associated lymph node metastasis of the same patient, and transitional cell carcinoma. To assess the suitability of the model system, the targets of masitinib were investigated by immunocytochemistry in the cell lines and by immunohistochemistry in the respective formalin‐fixed, paraffin‐embedded (FFPE) original neoplastic tissue. After exposure to masitinib, cell viability, cell count, apoptosis induction, and protein expression of c‐Kit, Lyn, PDGFR‐α, and PDGFR‐β were assessed. To hedge the efficacy, two application protocols of masitinib (single application or 12‐h double‐dose regimen) were compared. Immunocytochemical and immunohistochemical analysis revealed increased Lyn, PDGFR‐α, and PDGFR‐β expression in cell lines and FFPE original neoplastic tissue compared to healthy prostate tissue. Masitinib exposure increased apoptosis, while the cell counts and cell viability decreased in a dose‐ and application interval‐dependent manner, with increased impact in the 12‐h double‐dose regimen. These in vitro effects of masitinib in canine prostate cancer and associated metastasis support further in vivo research and modifications of the clinical treatment protocol in future studies.

show abstract

Section: Discussionmentioning

confidence: 99%

Evaluation of the therapeutic potential of masitinib and expression of its specific targets c‐Kit, PDGFR‐α, PDGFR‐β, and Lyn in canine prostate cancer cell lines

Klose

Packeiser

Granados-Soler

et al. 2022

Vet Comparative Oncology

View full text Add to dashboard Cite

show abstract

“…To this regard, tryptase targeting through tryptase inhibitors, such as gabexate or nafamostat mesylate, could become an interesting strategy as a novel antiangiogenetic intervention in pancreatic cancer patients [86][87][88][89][90]. On the other hand, MC degranulation could be inhibited by c-KitR tyrosine kinase inhibitors, such as masitinib, as first applied in veterinary clinical oncology and then translated to humans for the treatment of PDAT patients, with interesting results, as reported by the only phase 3 clinical trial [91][92][93][94][95]. Finally, MCDPT and MCAPT could become potential predictive biomarkers of response to anti-c-Kit or anti-tryptase therapy, in order to to select patients with a higher risk as assessed by these biomarkers [96].…”

Section: Discussionmentioning

confidence: 99%

Mast Cells Positive for c-Kit Receptor and Tryptase Correlate with Angiogenesis in Cancerous and Adjacent Normal Pancreatic Tissue

Ammendola

Currò

Laface

et al. 2021

Cells

Self Cite

View full text Add to dashboard Cite

Background: Mast cells (MCs) contain proangiogenic factors, in particular tryptase, associated with increased angiogenesis in several tumours. With special reference to pancreatic cancer, few data have been published on the role of MCs in angiogenesis in both pancreatic ductal adenocarcinoma tissue (PDAT) and adjacent normal tissue (ANT). In this study, density of mast cells positive for c-Kit receptor (MCDP-c-KitR), density of mast cells positive for tryptase (MCDPT), area of mast cells positive for tryptase (MCAPT), and angiogenesis in terms of microvascular density (MVD) and endothelial area (EA) were evaluated in a total of 45 PDAT patients with stage T2–3N0–1M0. Results: For each analysed tissue parameter, the mean ± standard deviation was evaluated in both PDAT and ANT and differences were evaluated by Student’s t-test (p ranged from 0.001 to 0.005). Each analysed tissue parameter was then correlated to each other one by Pearson t-test analysis (p ranged from 0.01 to 0.03). No other correlation among MCDP-c-KitR, MCDPT, MCAPT, MVD, EA and the main clinical–pathological characteristics was found. Conclusions: Our results suggest that tissue parameters increased from ANT to PDAT and that mast cells are strongly associated with angiogenesis in PDAT. On this basis, the inhibition of MCs through tyrosine kinase inhibitors, such as masitinib, or inhibition of tryptase by gabexate mesylate may become potential novel antiangiogenetic approaches in pancreatic cancer therapy.

show abstract

“…Although, some therapeutic agents such as the tyrosine kinase inhibitors can target several protooncogenes and decelerate the growth and recurrence. For example, toceranib phosphate selectively targets mutant CD 117 or masitinib mesylate inhibits stem cell factor/c-KIT pathway [ 27 , 28 ]. However, current evidence has indicated that this therapeutic setup is not sufficient for disease annihilation as well.…”

Section: Discussionmentioning

confidence: 99%

Immunohistochemical and molecular profiling of CD 117, Oct-4, and Sox-2 in canine cutaneous mast cell tumor of the crossbred dogs in Faculty of Veterinary Science, Chulalongkorn University, Bangkok, Thailand

et al. 2021

View full text Add to dashboard Cite

Background and Aim: CD 117 (c-KIT) internal tandem duplication (ITD), octamer-binding transcription factor 4 (Oct-4), and sex-determining region Y-box 2 (Sox-2) may govern the oncogenicity and aggressiveness of canine cutaneous mast cell tumor (MCT) in the crossbred dogs. Thus, a comprehension of this matter may help us establishing a novel platform to treat the disease in those dogs. However, evidence has lacked so far. Thus, this study aimed to survey CD 117 ITD, Oct-4, and Sox-2 expressions and their relations to the 2-tier grading in a group of Thai crossbreed dogs. The study was done using polymerase chain reaction (PCR), Reverse transcription PCR (RT-PCR), and immunohistochemistry. Materials and Methods: Thirty-three MCT specimens graded by the 2-tier histopathology grading were collected from the crossbred and purebred dogs. CD 117 ITD was detected by conventional PCR and immunohistochemistry. While, Oct-4 and Sox-2 expression levels were determined at the protein and mRNA levels by immunohistochemistry and RT-PCR, respectively. The expression magnitude of each parameter was then related to the grades and breeds. Results: About 60.61% of specimens were low grade, while 39.39% were high grade. CD 117 ITD was not detected in all specimens. A significant increase of Oct-4 expression was found in the high-grade, crossbred dogs. Meanwhile, Sox-2 expressions were increased both in the purebred and crossbred dogs with high-grade MCT. Conclusion: The study finding has indicated that the level of Sox-2 expression may be a useful tumorigenic and prognostic biomarker because it correlates to the 2-tier grades but not dog breeds.

show abstract

An evaluation of masitinib for treating systemic mastocytosis

Cited by 13 publications

References 71 publications

Evaluation of the therapeutic potential of masitinib and expression of its specific targets c‐Kit, PDGFR‐α, PDGFR‐β, and Lyn in canine prostate cancer cell lines

Evaluation of the therapeutic potential of masitinib and expression of its specific targets c‐Kit, PDGFR‐α, PDGFR‐β, and Lyn in canine prostate cancer cell lines

Mast Cells Positive for c-Kit Receptor and Tryptase Correlate with Angiogenesis in Cancerous and Adjacent Normal Pancreatic Tissue

Immunohistochemical and molecular profiling of CD 117, Oct-4, and Sox-2 in canine cutaneous mast cell tumor of the crossbred dogs in Faculty of Veterinary Science, Chulalongkorn University, Bangkok, Thailand

Contact Info

Product

Resources

About