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)

Lung cancer is one of the commonest causes of cancer death in developed countries. Recent evidence suggests that angoigenesis is related to poor prognosis in many solid tumors including non-small cell lung cancer (NSCLC). Angiogenesis is regulated by a complex interaction among growth factors and cytokines and influenced by proteolytic enzymes such as plasminogen activators and matrix metalloproteases, expression of adhesion molecules, and distribution of extracellular matrices. Fibroblasts, macrophages, mast cells, and endothelial cells themselves also affect angiogenesis. This review concentrates on angiogenic growth factors including vascular endothelial growth factor, angiopoietins, platelet derived endothelial growth factor, and basic fibroblast growth factor, proteases, adhesion molecules including vascular endothelial cadherin and integrins, osteopontin, and mast cell products in tumor angiogenesis of NSCLC.
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PMID:Tumor angiogenesis of non-small cell lung cancer. 1253 73

The synthesis and biological evaluation of a homologous series of conjugates (9-13) of 2,5-diaziridinylbenzoquinone (DZQ) and 9-carbonylacridine, a DNA intercalating moiety, via a polymethylene unit (n=2-6) are described. In addition, the non-acridine compound 14, analogous to compound 12, and the 5-methyl-DZQ derivatized conjugate 15, an analog of compound 10, were also prepared. Through a Comet assay, compounds 9-13 were shown to produce DNA interstrand cross-links at submicromolar concentrations, consistent with K562 leukemia cells accumulating in the G2/M stage in the cell cycle. The cytotoxicity of compounds 9-15 was examined using a MTT assay on several human cancer cell lines, including chronic myeloid leukemia K562, the non-small cell lung cancers H596 and H460, and colon carcinoma cells BE and HT29. H460 and HT29 are rich in DT-diaphorase (DTD), and H596 and BE cells have negligible amounts of functional DTD. Under continuous exposure of drugs, except to the non-aziridine compound 19b, the IC50 values of all other compounds were determined to be in the range of 0.3-11.3 nM. Compound 10, which has a propyl linker group, was subjected to in vivo studies. When BDF1 mice with established mouse mammary carcinoma were treated with compound 10 (2 mg/kg at day 1 and 5 mg/kg at day 7), a significant delay (9-10 days) in cancer growth was recorded when compared to untreated controls. Furthermore, administration of compound 10 to nu/nu BDF1 mice bearing human lung cancer H460 xenograft (1.5 mg/kg for 10 for five consecutive days from day 13 and 17) also showed a significant reduction in tumor growth compared to untreated controls. The half-life of compound 10 in the presence of five different peptidases (porcine esterase, carboxypeptidase A, B and Y, and pepsin) was determined to be between 30 and 60 h.
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PMID:Synthesis and biological evaluation of novel diaziridinylquinone-acridine conjugates. 1450 82

BACKGROUND: Mast cells have been documented to have several key functions with regards to malignant neoplasms. However, the functional significance of their accumulation is largely unknown. An analysis of the mast cell profile in mediastinal lymph nodes from lung cancer patients is reported here. METHODS: One hundred thirty-four, randomly selected lymph nodes (63 with positive pathological lymph node status) from 39 surgically treated lung cancer patients were examined. All cancer negative nodes were obtained from stage I patients. Mast cells were stained with Alcian blue and safranin O. Metastatic cancer cells were stained using anti-cytokeratin antibody. RESULTS: Immunohistochemical studies with cytokeratin revealed micro metastasis in 9/71 (12.68%) nodes previously diagnosed as histological negative. In tumor-free mediastinal lymph nodes, the mast cell count was significantly higher than in metastatic nodes. In all cases, mast cells were observed primarily in the T-cell area. CONCLUSIONS: An inverse relationship was observed between the number of mast cells and the amount of tumor tissue. The presence of mast cells primarily in the T-cell area implies a relationship between mast cells and the T-cell system. From the present study it is not possible to conclude whether mast cells in lymph nodes are for or against tumor spread.
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PMID:Distribution of Mast Cells in Mediastinal Lymph Nodes from Lung Cancer Patients. 1462 97

The association between inflammatory cells, including tumor associated macrophage (TAM), mast cell (MC) and eosinophil leucocyte (EL) densities and angiogenesis, as well as the relation of TAM, MC and EL densities and angiogenesis to tumor stage were investigated in specimens of 63 non-small cell lung carcinoma (NSCLC). Fifteen cases were in stage I, 12 were in stage II, 33 were in stage III and 3 were in stage IV. ELs and MCs were identified by hematoxilen-eosin and toluidine-blue histochemical stains, respectively. TAMs were shown by immunohistochemistry for CD68. Microvessels demonstrated by immunohistochemistry for CD31 were quantified by a stereological method and vascular surface density (VSD) and microvessel number (NVES) were calculated. There was not any statistically significant correlation between tumor's stage and VSD, TAM and EL counts. MC count and NVES were found to be higher in early stages. VSD and NVES were not associated with EL, MC and TAM counts. The lack of consistent correlation of angiogenesis to the stage of disease in this study supports the view that tumor angiogenesis is not a significant prognostic factor in NSCLCs. The absence of correlation between MCs, ELs and TAM counts and angiogenesis and absence of any relation between ELs and TAMs and tumor stage are discordant with the results of some of the previous studies in NSCLCs and in other tumors. The differing results may be due to wide variations in methodologies which were used for demonstration of inflammatory cells and vessels and variations in the degree of activation and complexity of functions of these cells.
Lung Cancer 2004 Jan
PMID:Association of macrophages, mast cells and eosinophil leukocytes with angiogenesis and tumor stage in non-small cell lung carcinomas (NSCLC). 1469 36

The clinical application of tyrosine kinase inhibitors for cancer treatment represents a therapeutic breakthrough. The rationale for developing these compounds rests on the observation that tyrosine kinase enzymes are critical components of the cellular signaling apparatus and are regularly mutated or otherwise deregulated in human malignancies. Novel tyrosine kinase inhibitors are designed to exploit the molecular differences between tumor cells and normal tissues. Herein, we will review the current state-of-the-art using agents that target as prototypes Bcr-Abl, platelet-derived growth factor receptor (PDGFR), KIT (stem cell factor receptor), and epidermal growth factor receptor (EGFR). These compounds are remarkably effective in treating diverse cancers that are highly resistant to conventional treatment, including various forms of leukemia, hypereosinophilic syndrome, mast cell disease, sarcomas, and lung cancer. It is now clear that the molecular defects underlying cancer can be targeted with designer drugs that yield striking salutary effects with minimal toxicity.
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PMID:Tyrosine kinase inhibitors and the dawn of molecular cancer therapeutics. 1582 81

We have previously demonstrated that adrenomedullin (AM) plays a critical role as an autocrine/paracrine tumor cell survival factor. We now present evidence that AM is an important regulator of mast cell (MC) function and that this modulation is potentially involved in tumor promotion. AM induced histamine or beta-hexosaminidase release from rat and human MCs through a receptor-independent pathway. AM was chemotactic for human MCs and stimulated mRNA expression of vascular endothelial growth factor, monocyte chemoattractant protein-1, and basic fibroblast growth factor in this cell type. Differentiated but not undifferentiated human MCs responded to hypoxic insult with elevated AM mRNA/protein expression. Using confocal microscopy, we identified AM-producing MCs in tumor infiltrates of human breast and lung cancer patients. In mixed culture assays the AM-producing human MC line HMC-1 augmented both anchorage-dependent and -independent growth of human lung cancer A549 cells, an effect that was suppressed by MC-targeted siRNA AM knockdown. Finally, HMC-1 cells induced in vivo angiogenesis as assessed by directed in vivo angiogenesis assay analysis; neutralizing anti-AM monoclonal antibody blocked this ability. Our collective data suggest a new role for AM as a cross-talk molecule that integrates tumor and MC communication, underlying a unique promotion mechanism of human cancers.
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PMID:Adrenomedullin is a cross-talk molecule that regulates tumor and mast cell function during human carcinogenesis. 1640 30

Endostar, approved for the treatment of non-small-cell lung cancer by the State Food and Drug Administration in China, is a derivative of human endostatin that is modified with an additional metal-chelating sequence (MGGSHHHHH) at the N-terminus. This modification contributes to an additional zinc-binding site in the endostatin sequence. In the present study, zinc-binding and zinc-free endostar were compared to further characterize their biochemical and structural properties. Thermally induced denaturation was determined by monitoring changes in fluorescence emission spectra. The data indicated that zinc binding significantly increased the transition temperature of endostar and contributed to a reversible change in protein conformation after recooling. Proteolysis assays demonstrated that the modified protein binding with zinc ions can stabilize the N-terminus and the C-terminus of endostar when treated with trypsin, chymotrypsin and carboxypeptidase A and B. Western-blot analyses using anti-His6 antibody confirmed that the major cleaved fragments of endostar were in the N-terminus when treated with trypsin and chymotrypsin. In the proliferation assay with human umbilical-vein endothelial cells, the zinc-binding and zinc-free endostar samples with extra zinc-binding sites displayed similar inhibiting activities.
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PMID:N-terminal modification increases the stability of the recombinant human endostatin in vitro. 1952 21

Hesperidin is a naturally occurring flavonoid that has been reported to possess anticancer effects. The purpose of this study is to evaluate the effect of hesperidin in modulating the expressions of cyclooxygenase-2 (COX-2), mast cells (MCs) and matrix metalloproteinases (MMPs) during benzo(a)pyrene (B(a)P) induced lung carcinogenesis in mice. B(a)P (50 mg/kg body weight) induced animals showed increased mast cell density (MCD) as revealed by toluidine blue staining and severe expression of COX-2 along with upregulated expression of MMP-2 and MMP-9 as revealed by Western blotting and immunohistochemistry. Supplementation of hesperidin (25 mg/kg body weight) to lung cancer bearing mice attenuated MCD and downregulated the expressions of COX-2, MMP-2 and MMP-9. These observations show that hesperidin exerts its anti-carcinogenic activity against lung cancer by altering the expressions of COX-2, MMP-2 and MMP-9.
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PMID:Modulatory effect of hesperidin on benzo(a)pyrene induced experimental lung carcinogenesis with reference to COX-2, MMP-2 and MMP-9. 2088 88

Several TLR agonists are effective in tumor immunotherapy, but their early innate mechanisms of action, particularly those of TLR2 agonists, are unclear. Mast cells are abundant surrounding solid tumors where they are often protumorigenic and enhance tumor angiogenesis. However, antitumor roles for mast cells have also been documented. The impact of mast cells may be dependent on their activation status and mediator release in different tumors. Using an orthotopic melanoma model in wild-type C57BL/6 and mast cell-deficient Kit(W-sh/W-sh) mice and a complementary Matrigel-tumor model in C57BL/6 mice, mast cells were shown to be crucial for TLR2 agonist (Pam(3)CSK(4))-induced tumor inhibition. Activation of TLR2 on mast cells reversed their well-documented protumorigenic role. Tumor growth inhibition after peritumoral administration of Pam(3)CSK(4) was restored in Kit(W-sh/W-sh) mice by local reconstitution with wild-type, but not TLR2-deficient, mast cells. Mast cells secrete multiple mediators after Pam(3)CSK(4) activation, and in vivo mast cell reconstitution studies also revealed that tumor growth inhibition required mast cell-derived IL-6, but not TNF. Mast cell-mediated anticancer properties were multifaceted. Direct antitumor effects in vitro and decreased angiogenesis and recruitment of NK and T cells in vivo were observed. TLR2-activated mast cells also inhibited the growth of lung cancer cells in vivo. Unlike other immune cells, mast cells are relatively radioresistant making them attractive candidates for combined treatment modalities. This study has important implications for the design of immunotherapeutic strategies and reveals, to our knowledge, a novel mechanism of action for TLR2 agonists in vivo.
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PMID:A critical role for mast cells and mast cell-derived IL-6 in TLR2-mediated inhibition of tumor growth. 2104 32

Tumour suppressor in lung cancer-1 (TSLC1) is a tumour-suppressor gene coding for an adhesion molecule that is expressed by mast cells. Reduced TSLC1 expression is associated with a poor prognosis in several human tumours, and this study sought to investigate if TSLC1 expression could be used to predict outcome in dogs with mast cell tumours (MCTs). Sections of MCTs of different tumour grades from 45 dogs (Group 1) were immunohistochemically assessed for TSLC1 and Ki67 expression. In addition, 35 intermediate-grade MCTs (Group 2) from dogs with known clinical follow-up were immunohistochemically stained for TSLC1 and Ki67. The TSLC1 staining intensity was found to strongly inversely correlate with tumour grade for Group 1 (P = 0.002857). For Group 2 there was a trend towards dogs with lower TSLC1 scores being more likely to die from MCT-related disease (P = 0.058). The intensity of TSLC1 staining inversely correlated with Ki67 expression for both groups.
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PMID:TSLC1 tumour-suppressor gene expression in canine mast cell tumours. 2106 8


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