-
FEBS Letters Feb 1991The biosynthesis of leukotrienes (LT) C4 and B4 is followed by an export of these mediators into the extracellular space. This transport was characterized using plasma...
The biosynthesis of leukotrienes (LT) C4 and B4 is followed by an export of these mediators into the extracellular space. This transport was characterized using plasma membrane vesicles prepared from mastocytoma cells and identified as an ATP-dependent primary active process. The apparent Km-values were 110 nM for LTC4 and 48 microM for ATP. The transport rate was highest for LTC4, whereas LTD4, LTE4, and N-acetyl-LTE4 were transported with relative rates of 31, 12 and 8%, respectively, at a concentration of 10 nM. LTB4 transport was also dependent on ATP. LTC4 transport was inhibited by LTD4 receptor antagonists (IC50 = 1.0 microM for MK-571 and 1.3 microM for LY245769) and by the inhibitor of leukotriene biosynthesis MK-886 (IC50 = 1.8 microM). The ATP-dependent export carrier for leukotrienes in leukotriene-synthesizing cells represents a novel member of the family of ATP-dependent exit pumps.
Topics: Adenosine Triphosphate; Animals; Cell Membrane; Eicosanoids; Leukotrienes; Mast-Cell Sarcoma; Mice; Mice, Inbred BALB C; Tumor Cells, Cultured
PubMed: 1899837
DOI: 10.1016/0014-5793(91)80256-3 -
Veterinary and Comparative Oncology Dec 2017CD30 is a novel therapeutic target in human mast cell (MC) neoplasms. In this 'comparative oncology' study, we examined CD30 expression and regulation in neoplastic...
CD30 is a novel therapeutic target in human mast cell (MC) neoplasms. In this 'comparative oncology' study, we examined CD30 expression and regulation in neoplastic canine MC using a panel of immunomodulatory cytokines [interleukin-2 (IL-2), IL-4, IL-5, IL-6, IL-13 and stem cell factor (SCF)] and the canine mastocytoma cell lines NI-1 and C2. Of all cytokines tested IL-4 was found to downregulate expression of CD30 in NI-1 and C2 cells. We also found that the CD30-targeting antibody-conjugate brentuximab vedotin induces growth inhibition and apoptosis in both MC lines. Next, we asked whether IL-4-induced downregulation of CD30 interferes with brentuximab vedotin-effects. Indeed, pre-incubation of NI-1 cells with IL-4 decreased responsiveness towards brentuximab vedotin. To overcome IL-4-mediated resistance, we applied drug combinations and found that brentuximab vedotin synergizes with the Kit-targeting drugs masitinib and PKC412 in inhibiting growth of NI-1 and C2 cells. In summary, CD30 is a new marker and IL-4-regulated target in neoplastic canine MC.
Topics: Animals; Antineoplastic Agents; Apoptosis; Benzamides; Brentuximab Vedotin; Cell Line, Tumor; Cytokines; Dog Diseases; Dogs; Down-Regulation; Drug Synergism; Female; Immunoconjugates; Interleukin-4; Ki-1 Antigen; Male; Mastocytosis; Piperidines; Pyridines; Staurosporine; Thiazoles
PubMed: 27507155
DOI: 10.1111/vco.12260 -
Veterinary and Comparative Oncology Mar 2018Mastocytoma are frequently diagnosed cutaneous neoplasms in dogs. In non-resectable mastocytoma patients, novel targeted drugs are often applied. The transcription...
BACKGROUND
Mastocytoma are frequently diagnosed cutaneous neoplasms in dogs. In non-resectable mastocytoma patients, novel targeted drugs are often applied. The transcription factor STAT5 has been implicated in the survival of human neoplastic mast cells (MC). Our study evaluated the JAK2/STAT5 pathway as a novel target in canine mastocytoma.
MATERIALS AND METHODS
We employed inhibitors of JAK2 (R763, TG101348, AZD1480, ruxolitinib) and STAT5 (pimozide, piceatannol) and evaluated their effects on 2 mastocytoma cell lines, C2 and NI-1.
RESULTS
Activated JAK2 and STAT5 were detected in both cell lines. The drugs applied were found to inhibit proliferation and survival in these cells with the following rank-order of potency: R763 > TG101348 > AZD1480 > pimozide > ruxolitinib > piceatannol. Moreover, synergistic anti-neoplastic effects were obtained by combining pimozide with KIT-targeting drugs (toceranib, masitinib, nilotinib, midostaurin) in NI-1 cells.
CONCLUSION
The JAK2/STAT5 pathway is a novel potential target of therapy in canine mastocytoma.
Topics: Animals; Apoptosis; Cell Line, Tumor; Cell Proliferation; Dog Diseases; Dogs; Flow Cytometry; Janus Kinase 2; Mastocytoma; Nitriles; Norbornanes; Pimozide; Pyrazoles; Pyrimidines; Pyrrolidines; STAT5 Transcription Factor; Signal Transduction; Stilbenes; Sulfonamides
PubMed: 28397975
DOI: 10.1111/vco.12311 -
Cureus Dec 2023Congenital cutaneous mastocytoma is an uncommon disorder characterized by abnormal proliferation of mast cells. It typically presents as a single, small,...
Congenital cutaneous mastocytoma is an uncommon disorder characterized by abnormal proliferation of mast cells. It typically presents as a single, small, yellowish-brown plaque, and its diagnosis is generally facilitated by distinctive clinical features, including a positive Darrier's sign. This report presents a case of an unusually large, solitary congenital mastocytoma encompassing nearly the entire circumference of the calf, observed in a newborn boy of Bangladeshi origin. Measuring 13x6 cm, the lesion formed large bullae and subsequent erosions. The perplexing clinical appearance prompted a skin biopsy, revealing monomorphic CD117 (c-KIT) positive infiltration without significant cell pleomorphism, confirming the diagnosis of cutaneous mastocytoma. The patient underwent management with potent and very potent topical steroids, oral antihistamines, and non-adhesive dressings, remaining under long-term follow-up with secondary care dermatology. In reporting this case, our objective is to augment the existing scientific literature by providing additional evidence that cutaneous mastocytomas can display a spectrum of clinical presentations, as illustrated in this case.
PubMed: 38205464
DOI: 10.7759/cureus.50306 -
Clinical Case Reports Sep 2023The diagnosis of solitary mastocytoma is usually made clinically, however, atypical presentations may obscure the diagnosis. We present a unique case of solitary...
The diagnosis of solitary mastocytoma is usually made clinically, however, atypical presentations may obscure the diagnosis. We present a unique case of solitary cutaneous mastocytoma in an 11-month-old male initially misdiagnosed as atopic dermatitis; the diagnosis was obscured due to the development of an allergic contact dermatitis most likely secondary to topical medications that were being applied to the lesion. The diagnosis of solitary cutaneous mastocytoma is made based on lesion morphology, Darier's sign, and lack of systemic involvement. Most solitary cutaneous mastocytomas resolve before puberty; symptomatic treatment and avoidance of triggers are mainstay therapy.
PubMed: 37705587
DOI: 10.1002/ccr3.7907 -
Scientific Reports May 2024The Nova Scotia Duck Tolling Retriever (NSDTR) is predisposed to immune mediated rheumatic disease (IMRD), steroid-responsive meningitis-arteritis (SRMA) and certain...
The Nova Scotia Duck Tolling Retriever (NSDTR) is predisposed to immune mediated rheumatic disease (IMRD), steroid-responsive meningitis-arteritis (SRMA) and certain forms of cancer. Cytokines are the main regulators of the immune system. Interleukin 2 is a cytokine involved in activation of T regulatory cells, playing a role in central tolerance and tumor immunity. Interleukin 12 and interleukin 23 share the same subunit, p40, and are both pro-inflammatory cytokines. The aim of this study was to compare levels of IL-2 in healthy NSDTRs to those with cancer or autoimmune disease and to compare levels of IL-12/IL-23p40 in healthy NSDTRs and beagles versus NSDTRs with cancer or autoimmune disease. 62 dogs were included in the analysis of IL-12/IL-23p40; healthy NSDTRs (n = 16), healthy beagles (n = 16), NSDTRs autoimmune (n = 18) and NDSTRs lymphoma/mastocytoma (n = 12) and 68 dogs for IL-2; healthy (n = 20), autoimmune (n = 36) and lymphoma/mastocytoma/adenocarcinoma (n = 12). NSDTRs with autoimmune disease had higher levels of IL-12/IL-23p40 compared to healthy dogs (p = 0.008). NSDTRs with lymphoma also had higher levels of IL-12/IL-23p40 compared to healthy NSDTRs (p = 0.002). There was no difference in levels of IL-2 between healthy and diseased NSDTR. Statistical analysis was performed using Bonferroni corrections for multiple testing. These findings can contribute to the knowledge of autoimmune disease and cancer in dogs.
Topics: Animals; Dogs; Autoimmune Diseases; Lymphoma; Dog Diseases; Interleukin-12; Female; Male; Interleukin-23; Interleukin-2
PubMed: 38773194
DOI: 10.1038/s41598-024-62265-y -
Clinical and Experimental Dermatology Sep 2022Mastocytosis is characterized by the accumulation of mast cells (MCs) in the skin or other organs, and can manifest at any age. A significant number of paediatric...
BACKGROUND
Mastocytosis is characterized by the accumulation of mast cells (MCs) in the skin or other organs, and can manifest at any age. A significant number of paediatric mastocytosis cases persist after puberty. In particular, monomorphic maculopapular cutaneous mastocytosis (mMPCM) is often persistent and associated with systemic mastocytosis. However, clinical differentiation of MPCM from polymorphic (p)MPCM can be difficult.
AIM
To identify histopathological features that can help to distinguish mMPCM from other subtypes of paediatric mastocytosis.
METHODS
This was a retrospective study using skin biopsies from patients with any subtype of mastocytosis. The localization and density of the MC infiltrate, MC morphology and expression of aberrant markers were evaluated and correlated with clinical characteristics.
RESULTS
In total, 33 biopsies were available for evaluation from 26 children [(10 with mMPCM, 5 with mastocytoma, 3 with diffuse cutaneous mastocytosis (DCM), 8 with pMPCM)] and 7 adults with MPCM. The MC number was increased in all patients, but was higher in children than adults (P < 0.01). The presence of mMPCM was associated with sparing of the papillary dermis from MC infiltration, whereas MC density in the papillary dermis was highest in pMPCM and DCM (P < 0.01). The positive predictive value of the presence of a reticular MC infiltrate for mMPCM was 72.7% (95% CI 51.4-87.0), and the negative predictive value was 83.3% (95% CI 42.2-97.2). There were no relevant differences in the expression of CD2, CD25 or CD30 between the different subtypes.
CONCLUSION
Skin histopathology might enhance the phenotypical differentiation of mMPCM from other subtypes in children, thereby increasing the accuracy of one's prognosis.
Topics: Adult; Child; Humans; Mast Cells; Mastocytosis; Mastocytosis, Cutaneous; Mastocytosis, Systemic; Proto-Oncogene Proteins c-kit; Retrospective Studies; Urticaria Pigmentosa
PubMed: 35596520
DOI: 10.1111/ced.15262 -
Frontiers in Microbiology 2016The influenza A viruses (IAVs) cause acute respiratory infection in both humans and animals. As a member of the initial lines of host defense system, the role of mast...
Influenza A Viruses Replicate Productively in Mouse Mastocytoma Cells (P815) and Trigger Pro-inflammatory Cytokine and Chemokine Production through TLR3 Signaling Pathway.
The influenza A viruses (IAVs) cause acute respiratory infection in both humans and animals. As a member of the initial lines of host defense system, the role of mast cells during IAV infection has been poorly understood. Here, we characterized for the first time that both avian-like (α-2, 3-linked) and human-like (α-2, 6- linked) sialic acid (SA) receptors were expressed by the mouse mastocytoma cell line (P815). The P815 cells did support the productive replication of H1N1 (A/WSN/33), H5N1 (A/chicken/ Henan/1/04) and H7N2 (A/chicken/Hebei/2/02) while the infection of H5N1 in mast cells was confirmed by the specific staining of nasal mucosa and lung tissue from mice. All the three viruses triggered the infected P815 cells to produce pro-inflammatory cytokines and chemokines including IL-6, IFN-γ, TNF-α, CCL-2, CCL-5, and IP-10, but not the antiviral type I interferon. It was further confirmed that TLR3 pathway was involved in P815 cell response to IAV-infection. Our findings highlight the remarkable tropism and infectivity of IAV to P815 cells, indicating that mast cells may be unneglectable player in the development of IAV infection.
PubMed: 28127293
DOI: 10.3389/fmicb.2016.02130 -
The Cornell Veterinarian Jan 1973
Topics: Animals; Cat Diseases; Cats; Granuloma; Mast-Cell Sarcoma; Skin Diseases; Skin Neoplasms
PubMed: 4631443
DOI: No ID Found -
Experimental Animals Apr 2000Spontaneous cutaneous mastocytomas in Djungarian hamsters (D-hamster) were pathologically studied and compared with those in canine and feline cases. Eight (9.3%) of 86... (Comparative Study)
Comparative Study
Spontaneous cutaneous mastocytomas in Djungarian hamsters (D-hamster) were pathologically studied and compared with those in canine and feline cases. Eight (9.3%) of 86 cutaneous biopsy cases in D-hamsters were diagnosed as mastocytomas, being slightly higher in incidence than in canine and feline species. In 4 of 8 D-hamster cases, the tumor lesions were in the head and neck in contrast to most canine lesions in the extremities. The histopathology of the D-hamster mastocytoma was characterized by diffuse or massive proliferation of well-differentiated tumor cells with severe degeneration of collagen fibers and slight eosinophil infiltration in most cases.
Topics: Animals; Cats; Chymases; Cricetinae; Dogs; Female; Immunoenzyme Techniques; Male; Mast Cells; Mast-Cell Sarcoma; Phodopus; Proliferating Cell Nuclear Antigen; Serine Endopeptidases; Skin Neoplasms; Species Specificity; Tryptases
PubMed: 10889951
DOI: 10.1538/expanim.49.127