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Proceedings of the National Academy of... Apr 1990Mouse serosal mast cells (SMCs) and Kirsten sarcoma virus-immortalized mast cells store large amounts of mast cell carboxypeptidase A and serine proteases in their...
Mouse serosal mast cells (SMCs) and Kirsten sarcoma virus-immortalized mast cells store large amounts of mast cell carboxypeptidase A and serine proteases in their secretory granules. Secretory granule proteins from 2.6 x 10(6) purified SMCs were separated by NaDodSO4/PAGE, trans-blotted to poly(vinylidine difluoride) membranes, and subjected to amino-terminal amino acid sequencing. Four distinct mast cell serine proteases were identified. With mast cell carboxypeptidase A, these serine proteases comprise the major proteins of mouse SMC secretory granules. Each of the four SMC serine proteases was distinct from the two serine proteases present in mucosal mast cells in the intestines of helminth-infected mice. The secretory granules of a Kirsten sarcoma virus-immortalized mast cell line contained three of the SMC-derived serine proteases and one of the mucosal mast cell-derived serine proteases. Thus, the family of mouse mast cell secretory granule serine proteases has at least six distinct members that can be expressed in different combinations in different mast cell populations.
Topics: Amino Acid Sequence; Animals; Bone Marrow; Cells, Cultured; Chymotrypsin; Esterases; Isoflurophate; Mast Cells; Mice; Mice, Inbred BALB C; Molecular Sequence Data; Protein Binding; Serine Endopeptidases; Trypsin
PubMed: 2326280
DOI: 10.1073/pnas.87.8.3230 -
Frontiers in Veterinary Science 2023Plasmablastic lymphoma (PBL) is a rare form of lymphoma in people. PBL originates from plasmablasts and usually presents with swelling/mass in the mouth/neck. A...
Plasmablastic lymphoma (PBL) is a rare form of lymphoma in people. PBL originates from plasmablasts and usually presents with swelling/mass in the mouth/neck. A 7-year-old Mongrel dog was presented for a large oral and neck mass. Cytology and histopathology were suggestive of a round cell tumor that was suspected to be lymphoma. An immunohistochemical (IHC) stain panel showed positive for CD18, thus supporting the diagnosis of round cell tumor, but negative for T- and B-cell lymphomas, CD3, CD20, and PAX-5. Other markers including cytokeratin AE1/3 (for epithelial cell origin), CD31 (for endothelial cells), SOX10 (for melanoma), IBa-1 (for histiocytic sarcoma), and CD117 (for mast cell tumor) were all negative. MUM-1 (for plasma cell differentiation) was strongly positive and CD79a (B cell and plasma cells) was also scantly positive. Based on the histopathology and immunohistochemistry results in combination with the clinical presentation, a suspected diagnosis of PBL was made. As per available literature, this is perhaps the first highly suspected case of PBL in a dog.
PubMed: 36875999
DOI: 10.3389/fvets.2023.1100942 -
The Journal of Veterinary Medical... Dec 2012A case of mast cell sarcoma in a 5-month-old Holstein female calf is described. Macroscopically, enlargement of the spleen, lymph nodes, tonsils and kidneys was noted,...
A case of mast cell sarcoma in a 5-month-old Holstein female calf is described. Macroscopically, enlargement of the spleen, lymph nodes, tonsils and kidneys was noted, and there were tumor masses in the neck region and on the pleura and peritoneum. The pericardium and uterine and ureter walls were also involved by tumor. Most neoplastic cells had eosinophilic granules, which were metachromatic and positive for naphthol AS-D chloroacetate esterase and tryptase, whereas smaller numbers of cells were positive for factor VIII-related antigen, a marker of megakaryocytes. Some of the predominant type of these tumor cells were found within the epithelia of the lungs, tonsils, gastrointestinal tract, liver, ureters, urinary bladder and uterus. Their normal counterparts were considered to be globule leukocytes.
Topics: Animals; Biomarkers, Tumor; Cattle; Cattle Diseases; Esterases; Factor VIII; Fatal Outcome; Female; Mast-Cell Sarcoma; Megakaryocytes; Naphthols; Tryptases
PubMed: 22813945
DOI: 10.1292/jvms.12-0236 -
The Journal of Biological Chemistry Nov 1989Mast cell carboxypeptidase A has been isolated from the secretory granules of mouse peritoneal connective tissue mast cells (CTMC) and from a mouse Kirsten sarcoma... (Comparative Study)
Comparative Study
Mast cell carboxypeptidase A has been isolated from the secretory granules of mouse peritoneal connective tissue mast cells (CTMC) and from a mouse Kirsten sarcoma virus-immortalized mast cell line (KiSV-MC), and a cDNA that encodes this exopeptidase has been cloned from a KiSV-MC-derived cDNA library. KiSV-MC-derived mast cell carboxypeptidase A was purified with a potato-derived carboxypeptidase-inhibitor affinity column and was found by analytical sodium dodecyl sulfate-polyacrylamide gel electrophoresis to be a Mr 36,000 protein. Secretory granule proteins from KiSV-MC and from mouse peritoneal CTMC were then resolved by preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis and transblotted to polyvinylidine difluoride membranes. Identical aminoterminal amino acid sequences were obtained for the prominent Mr 36,000 protein present in the granules of both cell types. Based on the amino-terminal sequence, an oligonucleotide probe was synthesized and used to isolate a 1,470-base pair cDNA that encodes this mouse exopeptidase. The deduced amino acid sequence revealed that, after cleavage of a 15-amino acid hydrophobic signal peptide and a 94-amino acid activation peptide from a 417-amino acid preproenzyme, the mature mast cell carboxypeptidase A protein core has a predicted Mr of 35,780 and a high positive charge [Lys + Arg) - (Asp + Glu) = 17) at neutral pH. Although critical zinc-binding amino acids (His67, Glu70, His195), substrate-binding amino acids (Arg69, Asn142, Arg143, Tyr197, Asp255, Phe278), and cysteine residues that participate in intrachain disulfide bonds (Cys64-Cys77, Cys136-Cys159) of pancreatic carboxypeptidases were also present in mast cell carboxypeptidase A, the overall amino acid sequence identities for mouse mast cell carboxypeptidase A relative to rat pancreatic carboxypeptidases A1, A2, and B were only 43, 41, and 53%, respectively. RNA and DNA blot analyses revealed that mouse peritoneal CTMC, KiSV-MC, and bone marrow-derived mast cells all express a prominent 1.5-kilobase mast cell carboxypeptidase A mRNA which is transcribed from a single gene. We conclude that mouse mast cell carboxypeptidase A is a prominent secretory granule enzyme of mast cells of the CTMC subclass and represents a novel addition to the carboxypeptidase gene family.
Topics: Amino Acid Sequence; Animals; Base Sequence; Carboxypeptidases; Carboxypeptidases A; Cloning, Molecular; DNA; Genes; Mast Cells; Mice; Molecular Sequence Data; Multigene Family; Pancreas; RNA, Messenger; Rats; Sequence Homology, Nucleic Acid
PubMed: 2584208
DOI: No ID Found -
Journal of Veterinary Internal Medicine 2012Mast cell tumors (MCT) are common cutaneous tumors in dogs and when not amenable to surgical excision can present a therapeutic challenge. New treatment protocols for... (Clinical Trial)
Clinical Trial
BACKGROUND
Mast cell tumors (MCT) are common cutaneous tumors in dogs and when not amenable to surgical excision can present a therapeutic challenge. New treatment protocols for unresectable MCT are needed.
HYPOTHESIS
The combination of toceranib, prednisone, and hypofractionated radiation treatment (RT) will be well tolerated and efficacious.
ANIMALS
Seventeen client-owned dogs with measurable MCT amenable to RT.
METHODS
Prospective clinical trial. All dogs received prednisone, omeprazole, diphenhydramine, and toceranib. Toceranib was administered for 1 week before initiating RT, consisting of 24 Gy delivered in 3 or 4 fractions.
RESULTS
On an intent-to-treat basis, the overall response rate was 76.4%, with 58.8% of dogs achieving a complete response and 17.6% a partial response. The median time to best response was 32 days, and the median progression-free interval was 316 days. The overall median survival time was not reached with a median follow-up of 374 days. The most common toxicoses were gastrointestinal and hepatic.
CONCLUSIONS AND CLINICAL IMPORTANCE
The combination of hypofractionated RT, toceranib, and prednisone was tolerated and efficacious in the majority of dogs. Response rates and durations were higher than those reported for toceranib as a single-agent treatment for MCT. This combination is a viable treatment option for unresectable MCT.
Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; DNA, Neoplasm; Disease-Free Survival; Dog Diseases; Dogs; Female; Indoles; Kaplan-Meier Estimate; Male; Mast-Cell Sarcoma; Polymerase Chain Reaction; Prednisone; Prospective Studies; Proto-Oncogene Proteins c-kit; Pyrroles; Radiography; Skin Neoplasms
PubMed: 22176473
DOI: 10.1111/j.1939-1676.2011.00851.x -
Journal of the American Veterinary... Jun 2011To evaluate the relationship between width and depth of surgical margins, amount of edema within and around the tumor, and degree of demarcation between the tumor and...
OBJECTIVE
To evaluate the relationship between width and depth of surgical margins, amount of edema within and around the tumor, and degree of demarcation between the tumor and surrounding tissues with the clinical outcome following surgical removal of cutaneous mast cell tumors (cMCTs) in dogs.
DESIGN
Retrospective cohort study.
ANIMALS
100 dogs with 115 resectable cMCTs.
PROCEDURES
Information about the dogs' clinical outcomes following cMCT removal was obtained from primary care veterinarians. Histologic sections of excised tumors were assessed retrospectively for tumor grade and measurement of the narrowest lateral and deep margins of nonneoplastic tissue excised with the tumors; edema within the tumor and surrounding tissues was assessed as minimal, moderate, or severe. Tumors were classified as poorly, moderately, or well demarcated on the basis of the degree of mast cell infiltration into the adjoining connective tissue.
RESULTS
Following tumor excision (with no additional postsurgery treatment), 96 dogs had no local recurrence or metastatic disease for 27 to 31 months; 4 metastatic disease-related deaths (dogs with grade II or III tumors) occurred within 3 to 9 months. Histologically, mean lateral and deep surgical margins around the tumors were 8.9 and 5.3 mm, respectively. No recurrence of tumor or metastatic disease developed following excision with lateral margins ≥ 10 mm and deep margins ≥ 4 mm. Edema and degree of demarcation were not correlated with outcome.
CONCLUSIONS AND CLINICAL RELEVANCE
Results suggested that most grade I and II cMCTs in dogs can be successfully treated by complete surgical removal with margins smaller than those currently recommended.
Topics: Animals; Cohort Studies; Dog Diseases; Dogs; Edema; Female; Male; Mast-Cell Sarcoma; Neoplasm Metastasis; Neoplasm Recurrence, Local; Neoplasm Staging; Retrospective Studies; Skin Neoplasms; Treatment Outcome
PubMed: 21627510
DOI: 10.2460/javma.238.11.1464 -
The Journal of Biological Chemistry Oct 1997In prior work we showed that a metallogelatinase is secreted from dog mastocytoma cells and directly activated by exocytosed mast cell alpha-chymase. The current work...
In prior work we showed that a metallogelatinase is secreted from dog mastocytoma cells and directly activated by exocytosed mast cell alpha-chymase. The current work identifies the protease as a canine homologue of progelatinase B (92-kDa gelatinase, MMP-9), determines the sites cleaved by alpha-chymase, and explores the regulation of gelatinase expression in mastocytoma cells. To obtain a cDNA encoding the complete sequence of mastocytoma gelatinase B, a 2. 3-kilobase clone encoding progelatinase was isolated from a BR mastocytoma library. The sequenced cDNA predicts a 704-amino acid protein 80% identical to human progelatinase B. Regions thought to be critical for active site latency, such as the Cys-containing propeptide sequence, PRCGVPD, and the catalytic domain sequence, HEFGHALGLDHSS, are entirely conserved. Cleavage of progelatinase B by purified dog alpha-chymase yielded an approximately 84-kDa product that contained two NH2-terminal amino acid sequences, QTFEGDLKXH and EGDLKXHHND, which correspond to residues 89-98 and 92-101 of the cDNA predicted sequence, respectively. Thus, alpha-chymase cleaves the catalytic domain of gelatinase B at the Phe88-Gln89 and Phe91-Glu92 bonds. Like BR cells, the C2 line of dog mastocytoma cells constitutively secrete progelatinase B which is activated by alpha-chymase. By contrast, non-chymase-producing C1 cells secrete a gelatinase B (which remains in its proform) only in response to 12-O-tetradecanoylphorbol-13-acetate. Whereas 12-O-tetradecanoylphorbol-13-acetate stimulation of BR cells produced a approximately 15-fold increase in gelatinase B mRNA expression, dexamethasone down-regulated its expression by approximately 5-fold. Thus, extracellular stimuli may regulate the amount of mast cell progelatinase B expressed by mast cells. These data further support a role for mast cell alpha-chymase in tissue remodeling involving gelatinase B-mediated degradation of matrix proteins.
Topics: Amino Acid Sequence; Animals; Base Sequence; Binding Sites; Catalysis; Chymases; Collagenases; DNA, Complementary; Dogs; Down-Regulation; Enzyme Activation; Enzyme Precursors; Gelatinases; Glutamine; Humans; Mast Cells; Mast-Cell Sarcoma; Metalloendopeptidases; Molecular Sequence Data; Phenylalanine; RNA, Messenger; Serine Endopeptidases; Tumor Cells, Cultured
PubMed: 9325284
DOI: 10.1074/jbc.272.41.25628 -
Oncology Letters Sep 2019The present case report investigated the clinical characteristics of primary hematological malignancy of the uterine cervixin five patients. Among the five patients,...
The present case report investigated the clinical characteristics of primary hematological malignancy of the uterine cervixin five patients. Among the five patients, three patients were diagnosed with non-Hodgkin's lymphoma (NHL) and two patients with myeloid sarcoma (MS) of the uterine cervix. Biopsies of the uterine cervices demonstrated the involvement of lymphoid cells or myeloid blasts cells. Immunohistochemical staining demonstrated the expression of B-lymphoid and myeloid lineage markers. The associated lysozyme, myeloperoxidase and mast/stem cell growth factor receptor (CD117) markers were specific for the diagnosis of MS. The three patients with NHL survived, and one of the patients survived for 82 months with no evidence of disease; however, was eventually lost to follow-up. The two patients with MS succumbed to the cancer as a result of progressive disease and leukemia. Therefore, pathological examination may be important for the timely diagnosis and appropriate therapeutic regimen for primary hematological malignancy of the uterine cervix.
PubMed: 31516559
DOI: 10.3892/ol.2019.10652 -
ISRN Veterinary Science 2013Cancer is a common problem in dogs and although all breeds of dog and crossbred dogs may be affected, it is notable that some breeds of pedigree dogs appear to be at...
Cancer is a common problem in dogs and although all breeds of dog and crossbred dogs may be affected, it is notable that some breeds of pedigree dogs appear to be at increased risk of certain types of cancer suggesting underlying genetic predisposition to cancer susceptibility. Although the aetiology of most cancers is likely to be multifactorial, the limited genetic diversity seen in purebred dogs facilitates genetic linkage or association studies on relatively small populations as compared to humans, and by using newly developed resources, genome-wide association studies in dog breeds are proving to be a powerful tool for unravelling complex disorders. This paper will review the literature on canine breed susceptibility to histiocytic sarcoma, osteosarcoma, haemangiosarcoma, mast cell tumours, lymphoma, melanoma, and mammary tumours including the recent advances in knowledge through molecular genetic, cytogenetic, and genome wide association studies.
PubMed: 23738139
DOI: 10.1155/2013/941275 -
BMC Veterinary Research Aug 2022Cell free DNA, in the form of nucleosomes, is released into circulation during apoptosis and necrosis in a variety of diseases. They are small fragments of chromosomes...
BACKGROUND
Cell free DNA, in the form of nucleosomes, is released into circulation during apoptosis and necrosis in a variety of diseases. They are small fragments of chromosomes that are composed of DNA wrapped around a histone core made of four duplicate histone proteins forming an octamer. The nucleosome compartment is a relatively uninvestigated area of circulating tumor biomarkers in dogs. The objectives of this study were to quantify and better characterize nucleosome concentrations in 528 dogs with various common malignancies and compare them to 134 healthy dogs.
RESULTS
The sensitivity of increased circulating nucleosome concentrations for the detection of cancer in all dogs was 49.8% with a specificity of 97% with an area under the curve of 68.74%. The top 4 malignancies detected by the test included lymphoma, hemangiosarcoma, histiocytic sarcoma and malignant melanoma. The malignancies least likely to be detected were soft tissue sarcomas, osteosarcoma and mast cell tumors.
CONCLUSIONS
A variety of tumor types may cause increased nucleosome concentrations in dogs. Tumors of hematopoietic origin are most likely to cause elevations and local tumors such as soft tissue sarcomas are least likely to cause elevations in plasma nucleosome concentrations.
Topics: Animals; Bone Neoplasms; Dog Diseases; Dogs; Histones; Nucleosomes; Sarcoma
PubMed: 36045415
DOI: 10.1186/s12917-022-03429-8