Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Photoradiation therapy, a new method for treatment of solid malignant tumors, depends upon the tumor localization and retention of hematoporphyrin derivative, which is activated in vivo by light in the red region of the spectrum. As currently applied to cutaneous and s.c. lesions, the light dose is limited by both normal tissue reactions and the effective penetration of the light through the tissues. In this report, primary solid malignant lesions in pet cats and dogs have been treated by interstitial photoradiation therapy by applying the activating light from a laser [635 +/- 5 (S. D.) nm] directly into the tumor masses thrugh a 200-micrometer quartz fiber optic. Twelve of 14 lesions (four osteosarcomas, two squamous cell carcinomas, two malignant melanomas, one mast cell sarcoma, one fibrosarcoma, one sebaceous gland sarcoma, and a metastatic prostatic carcinoma) responded to treatment, and three are currently considered permanently controlled at 1 year or more following treatment. This method has not only allowed photoradiation therapy to be applied to some remote lesions but has also nearly eliminated normal tissue effects, thus greatly extending the applicability of this treatment to a wide range of human tumors.
Cancer Res 1981 Feb
PMID:Interstitial photoradiation therapy for primary solid tumors in pet cats and dogs. 744 84

Involvement of the larynx by hemopoietic tumors is generally considered a rare event and little is known about the associated clinicopathologic features. Laryngeal tissue removed at autopsy from 14 patients with known disseminated hematologic malignancies and at operation from one patient with multicentric malignant lymphoma of low-grade malignancy (MALToma) of the head and neck region was investigated. A systematic survey of the main clinicopathologic features of the published cases of hemopoietic tumors with laryngeal involvement was also performed. Primary involvement of the larynx by hemopoietic neoplasms must be clearly distinguished from secondary involvement by disseminated or leukemic tumors. Most of the primary tumors are localized lesions that may involve the regional lymph nodes (stages IE or IIE). Radiotherapy is the treatment of choice, and the prognosis is generally favorable. However, secondary involvement by disseminated or leukemic disease carries a very poor prognosis in most cases. Extramedullary plasmacytoma and non-Hodgkin's lymphoma (NHL), particularly B-cell lymphoma of high-grade malignancy, appear to be the most common hemopoietic tumors with primary laryngeal involvement, while primary tumors of myelogenous origin (granulocytic sarcoma and mast cell sarcoma) are extremely rare. Extramedullary plasmacytoma and NHL occur mainly in older persons and in men, are generally associated with a relatively short history of hoarseness and dysphagia, and exhibit preferential involvement of the supraglottic parts of the larynx, in particular the epiglottis and aryepiglottic folds. They are generally polypoid, non-ulcerated lesions.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Involvement of the larynx by hemopoietic neoplasms. An investigation of autopsy cases and review of the literature. 756 82

Constitutive activation of the Abelson (Abl) protein tyrosine kinase (PTK) is a causative event in chronic myeloid leukemia, where intense chemotherapy currently fails to eradicate the leukemic clone. Using a mouse mast cell line (IC.DP), we previously showed that v-Abl PTK induced resistance to the anti-cancer drugs melphalan and hydroxyurea by the suppression of apoptosis. Here, using this cell line, we demonstrate by alkaline elution that v-Abl PTK did not affect the levels of DNA damage induced by either drug. This confirms that v-Abl PTK acts downstream of the drug-target interaction to prevent the coupling of drug-induced damage to the apoptotic pathway. Although Abl PTK- and interleukin-3 (IL-3)-stimulated signaling events share common signaling pathways, a similar level of drug resistance was not provided by IL-3, implying that Abl PTK does not merely mimic an IL-3 survival signaling pathway. Previously we demonstrated translocation of protein kinase C-beta II stimulated by activation of Abl PTK. Drug sensitivity was restored in cells with active v-Abl PTK by simultaneous addition of calphostin C, an inhibitor of protein kinase C, suggesting a role for protein kinase C in the suppression of drug-induced apoptosis by v-Abl PTK. One novel strategy for the treatment of chronic myeloid leukemia could therefore include the use of a downstream modifier of the Abl PTK-mediated survival signaling pathway to render leukemic cells more sensitive to a second drug, such as a cytotoxic agent.
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PMID:Characterization of drug resistance mediated via the suppression of apoptosis by Abelson protein tyrosine kinase. 765 67

Five tumours, which arose in cats naturally or experimentally infected with feline immunodeficiency virus (FIV), were examined with molecular probes to establish tumour cell lineage and to screen for integrated viral sequences. Three of the tumours were classed as B-cell lymphomas on the basis of morphology, immunocytochemistry, rearrangement of immunoglobulin heavy chain genes and lack of rearrangement of T-cell receptor (TCR) beta-chain genes. Two of these B-cell tumours arose in specific pathogen-free (SPF) cats experimentally infected with FIV. One case of multi-centric lymphosarcoma came from a cat naturally infected with both FIV and feline leukaemia virus (FeLV). This tumour contained integrated FeLV proviral sequences and was judged to be of T-cell origin on the basis of TCR gene rearrangement. The fifth case was a mast cell tumour. Rearrangement of the c-myc locus was not found in any of the FIV-associated tumours but was shown to be present in a rare immunoblastic B-cell lymphoma which arose in an uninfected SPF cat. None of the FIV-associated tumours showed evidence of integrated FIV sequences by Southern blot hybridisation, despite isolation of infectious virus from in vitro cultures of tumour cells in I case. These results confirm that FIV-associated tumours can occur in the absence of FeLV and suggest that the role of FIV in lymphomagenesis is generally indirect.
Int J Cancer 1995 Apr 10
PMID:Molecular analysis of tumours from feline immunodeficiency virus (FIV)-infected cats: an indirect role for FIV? 770 53

The occurrence of soft tissue tumors has been studied in 117 beagles assigned to 8 dosage groups of between 2 and 26 animals each and injected with 0.07 to 104 kBq 241Am kg-1 as the citrate. In addition, 133 control beagles given no radioactivity were used as a comparison group. All 250 dogs were maintained under identical conditions and were observed for their entire lifespans. An important competing risk for the appearance of soft tissue tumors appeared to be the occurrence of skeletal malignancy, and at the highest injected activity (104 kBq kg-1), kidney and liver failure brought about the death of both of the two dogs in this group. Thyroid and liver were the only soft tissues that exhibited greater concentrations of 241Am than the skeleton. Liver tumors were associated with 241Am exposure (p < 0.001), but the thyroid tumor rate was not increased significantly in the irradiated animals (p > 0.10) as compared with the occurrence in controls. There was a greater relative occurrence of all vaginal tumors in control animals than in dogs given 241Am, a situation also found for all tumors of the pancreas, skin, testis, and mammary glands and for malignant ovarian tumors. All of these differences were statistically significant. The survival of animals given 0.07 to 0.59 kBq 241Am kg-1 could not be established (p > 0.10) as significantly different from controls, but the survival of all groups given 1.8 to 104 kBq kg-1 was decreased (p < 0.05). There was no indication in our studies of a positive association between relative exposure to 241Am and the occurrence of mammary tumors, mast cell sarcomas originating outside the liver, lymphosarcoma or tumors of marrow, including leukemia.
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PMID:Soft tissue tumors in beagles injected with 241Am citrate. 781 56

Methotrexate-alpha-phenylalanine (MTX-Phe), a second-generation prodrug in the MTX alpha-peptide series designed for activation to MTX by carboxypeptidase-mAb conjugates, was synthesized by reaction of the p-nitrophenyl ester of 4-amino-4-deoxy-10-methylpteroic acid with L-glutamyl-alpha-L-phenylalanine. Production of MTX from MTX-Phe, catalyzed by bovine pancreas carboxypeptidase A (CPA), was 250-fold faster than the corresponding reaction involving methotrexate-alpha-alanine, previously the best MTX peptide substrate for the enzyme. The amount of CPA required to make MTX-Phe equitoxic with MTX, when tested against UCLA-P3 human lung adenocarcinoma cells in vitro, was more than 10-fold lower than that required to achieve the same result with MTX-alpha-alanine. When the lung tumor cells were treated with CPA conjugated to KS1/4 (a mAb targeted to these cells) and excess conjugate removed by extensive washing, the ID50 for MTX-Phe improved from 2.2 x 10(-6) M (no enzyme present) to 6.3 x 10(-8) M; the latter value was comparable to that of the parent drug MTX (4.5 x 10(-8) M). [3H]MTX-Phe was synthesized and used to investigate the mechanism by which the prodrug exerts its cytotoxic effect in the presence and absence of CPA. The present results demonstrate that, for use in conjunction with CPA-mAb conjugates, the alpha-phenylalanine derivative is the optimal prodrug form of MTX (and probably other antifols that contain the glutamate moiety).
Cancer Res 1995 Feb 01
PMID:Methotrexate-alpha-phenylalanine: optimization of methotrexate prodrug for activation by carboxypeptidase A-monoclonal antibody conjugate. 783 11

We have demonstrated for the first time that a conditioned medium from a human cell strain can induce morphologically mature mast cells that express Fc epsilon RI and three mast cell-specific proteases from normal bone marrow progenitor cells. In contrast, recombinant human Kit ligand induced the differentiation of mast cells that were tryptase-positive but negative for chymase, carboxypeptidase, and Fc epsilon RI. This data indicates that factors other than Kit ligand are critical for inducing the differentiation and maturation of mast cells in the human. The HBM-M cell was originally derived from a patient with mastocytosis. As mastocytosis is thought to represent a reactive hyperplasia rather than a mast cell malignancy, the factor secreted by the HBM-M cell strain could well be responsible for the mast cell hyperplasia seen in some patients with mastocytosis.
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PMID:Conditioned media from a cell strain derived from a patient with mastocytosis induces preferential development of cells that possess high affinity IgE receptors and the granule protease phenotype of mature cutaneous mast cells. 783 59

Interstitial cystitis, a sterile bladder condition, is characterized by urinary frequency, urgency, burning and suprapubic pain. Increasing evidence indicates that interstitial cystitis is a heterogeneous syndrome that reflects an immune response to a variety of triggers. More than 50% of the patients have allergies, 30% have the irritable bowel syndrome and almost 20% suffer from migraine headaches. Increased numbers of mast cells have been reported in interstitial cystitis. Mast cell activation, which is critical if these cells were to be implicated in this syndrome, has been investigated by electron microscopy, which definitively shows mast cell secretion. Recently, methylhistamine, the major metabolite of histamine, and the specific mast cell marker, tryptase, were shown to be significantly elevated in urine of interstitial cystitis patients. Bladder biopsies from 53 patients were analyzed blindly for the number and degree of activation of mast cells using 4 different stains for light microscopy, as well as electron microscopy. Controls included 16 patients with incontinence and chronic bacterial cystitis. Mast cells in controls were less than 10/mm.2 and were all nearly intact. Surprisingly, mast cells from 11 cancer patients averaged 50/mm.2 but almost all were intact. In contrast, mast cells from 26 interstitial cystitis patients averaged 40/mm.2 and more than 90% were activated to various degrees. Therefore, bladder mast cell activation is a characteristic pathological finding in at least a subset of patients with interstitial cystitis.
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PMID:Activation of bladder mast cells in interstitial cystitis: a light and electron microscopic study. 786 1

Interleukin-9 (IL-9) is a multifunctional cytokine produced by activated TH2 clones in vitro and during TH2-like T cell responses in vivo. The IL-9 receptor is a member of the hemopoietin receptor superfamily and interacts with the gamma chain of the IL-2 receptor for signal transduction. Various observations indicate that IL-9 is actively involved in mast cell responses by inducing the proliferation and differentiation of these cells. The role of IL-9 in T cell responses is less clear. Although freshly isolated normal T cells do not respond to IL-9, this cytokine induces the proliferation of murine T cell lymphomas in vitro and in vivo overexpression of IL-9 results in the development of thymic lymphomas. In the human, the existence of an IL-9-mediated autocrine loop has been suggested for some malignancies such as Hodgkin's disease. Other potential biological targets for IL-9 include B lymphocytes, hematopoietic progenitors, and immature neuronal cell lines.
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PMID:Interleukin-9 and its receptor: involvement in mast cell differentiation and T cell oncogenesis. 788 4

There is evidence that mast cells and their degranulation products are involved in resistance against tumours. Previously, we have shown that tumour incidence and growth were inversely correlated with basal histamine levels, i.e. mast cell numbers, in tissues of W/Wv (mast cell-deficient), Wv/+ (partially mast cell-depleted), and +/+ (mast cell-sufficient) mice, and that histamine levels were increased in numerous tissues of tumour-bearing animals, including C57BL/6 and C3H mice, Sprague-Dawley and Commentry rats. The aim of this work was to analyse the incidence and growth of a grafted tumour (fibrosarcoma MC-B6-1) in W/+ mice, as compared with W/Wv, Wv/+ and +/+ mice, and to study the modifications in tissue histamine levels in W/+, W/Wv, Wv/+ and +/+ tumour-grafted mice, in order to determine whether or not these modifications were correlated with resistance to tumours. We report confirmation that tumour incidence and growth are inversely correlated with basal tissue histamine levels in W/Wv, Wv/+, and +/+ fibrosarcoma-bearing mice. However, in W/+ mice (normal tissue histamine levels), tumour incidence was the same as in Wv/+ mice. Histamine levels in tissues of W/Wv, Wv/+, W/+ and +/+ tumour bearing mice were not significantly different from those in controls. They were higher in some tissues of Wv/+ mice rejecting the tumour than in Wv/+ mice not rejecting the tumour. However, in W/+ and +/+ mice, histamine levels were not significantly different, and even tended to be lower in most tissues of mice rejecting the tumour than in mice accepting the tumour. Overall, these results suggest that resistance to tumours cannot be ascribed solely to mast cells, and that other mechanisms may also be involved. Thus, further experiments are needed to clarify the exact role of mast cells and mast cell-derived mediators and cytokines in the defence against tumours.
Cancer Lett 1994 Sep 30
PMID:Modifications in tissue histamine levels in mast cell-deficient mice (W/Wv) and in their littermates (Wv/+, W/+ and +/+) grafted with a methylcholanthrene-induced fibrosarcoma: correlation with tumour rejection. 792 95


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