cyclic-gmp and Mouth-Neoplasms

The prognosis of patients with osteosarcoma is poor; therefore, new treatment strategies are urgently needed. Phosphodiesterase 2 (PDE2) is one of the 11 families (PDE1-PDE11) of the phosphodiesterase superfamily that regulates the intracellular concentrations and effects of cAMP and cGMP. This in vitro study was performed to investigate the role of PDE2 in human oral osteosarcoma HOSM-1 cells.. PDE2 expression was measured by a cAMP-PDE assay and real-time-PCR. The effects of the PDE2-specific inhibitors, erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA), 8-bromo-cAMP, and 8-bromo-cGMP on cell proliferation and migration were assessed.. PDE2 activity and PDE2A mRNA expression were detected in HOSM-1 cells. Cell proliferation was inhibited by EHNA and 8-bromo-cAMP but not by 8-bromo-cGMP. Cell migration was stimulated by EHNA and 8-bromo-cGMP, but it was inhibited by 8-bromo-cAMP.. Cell proliferation is regulated by PDE2-cAMP signaling and cell migration is regulated by PDE2-cGMP signaling in HOSM-1 cells.

Topics: Adenine; Apoptosis; Benzyl Compounds; Bone Neoplasms; Cell Cycle; Cell Movement; Cell Proliferation; Cyclic AMP; Cyclic GMP; Cyclic Nucleotide Phosphodiesterases, Type 2; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Humans; Mouth Neoplasms; Osteosarcoma; Signal Transduction; Tumor Cells, Cultured

The aim of the present study was to assess the role of the p38 mitogen-activated protein kinase (MAPK) pathway in the induction of inducible nitric oxide synthase (iNOS) expression and the production of NO by neutrophils (polymorphonuclear neutrophils [PMNs]) and peripheral blood mononuclear cells (PBMCs) in patients with squamous cell carcinoma (SCC) of the oral cavity.. PMNs and PBMCs were isolated from 24 patients with SCC. The expression of iNOS and phospho-p38 MAPK was estimated by Western blotting. Total NO was measured in the cell supernatants and serum using the Griess method. The generation of superoxide anion radicals by the cells was estimated using the cytochrome-c reduction test. The cyclic guanosine monophosphate level in the cell supernatants and plasma was assessed using an enzyme-linked immunosorbent assay kit, and the concentrations of malonyldialdehyde in serum were assessed using a thiobarbituric acid method.. The results of the present study of patients with stage II and III disease showed lowered expression of iNOS and phospho-p38 MAPK in PMNs and PBMCs. Moreover, in these patients, a lower production of NO by PMNs and PBMCs was observed. However, the opposite relationship was observed between the expression of phospho-p38 MAPK and iNOS in the leukocytes of patients with stage IV disease. The concentration of total NO in the PMN and PBMC supernatants of patients with advanced disease stages did not differ from that of the control group. In all the patients with SCC, a lowered ability of neutrophils to generate superoxide anion radicals and an increased production of cyclic guanosine monophosphate by PMNs and PBMCs was confirmed. Furthermore, a greater concentration of cyclic guanosine monophosphate was found in the plasma and total NO in the serum of patients with stage IV disease compared with the levels in the control group. A greater concentration of malonyldialdehyde in the serum of all patients compared with that in the control group was also observed.. Our results indicate that in the leukocytes of patients with stage II and III SCC, the p38 MAPK pathway performs an essential role in the induction of iNOS expression, and the process of lipid peroxidation is not dependent on NO. In contrast, in patients with advanced-stage SCC, iNOS expression did not seem to be linked with the p38 MAPK pathway, and NO directly influenced the process of lipid peroxidation.

Topics: Adult; Carcinoma, Squamous Cell; Case-Control Studies; Cyclic GMP; Enzyme Induction; Humans; Leukocytes, Mononuclear; Lipid Peroxidation; Malondialdehyde; Middle Aged; Mouth Neoplasms; Neutrophils; Nitric Oxide; Nitric Oxide Synthase Type II; p38 Mitogen-Activated Protein Kinases; Reference Values; Second Messenger Systems; Severity of Illness Index; Signal Transduction; Young Adult

In order to examine the cyclic nucleotides (cGMP) role in carcinoma growth and invasivity. We analyzed two cell lines, LSHT29 and 17GT, and tissues in patients with carcinoma and malignant tissues with (N+) and without (N-) lymph node metastases. Higher cGMP levels in pathological samples suggest a strong correlation between intracellular cGMP concentration and carcinoma progression.

Topics: Carcinoma; Carcinoma, Squamous Cell; Cell Line, Tumor; Chromatography, High Pressure Liquid; Cyclic GMP; Disease Progression; Gingival Neoplasms; Guanosine Monophosphate; Humans; Indicators and Reagents; Lymphatic Metastasis; Mouth Neoplasms; Quinolines

Numerous reports have documented a direct involvement of matrix metalloproteinase (MMP) overexpression in the development and progression of head and neck squamous cell carcinoma (HNSCC). In this study, the authors examined whether the expression of MMPs in HNSCC is correlated with other steps involved in tumor growth and metastasis, like angiogenesis, activation the nitric oxide (NO) pathway, and alteration of the p53 tumor suppressor gene.. MMP-1, MMP-2, and MMP-9 expression levels were examined immunohistochemically in samples from 43 patients with HNSCC. Microvessel density (MVD) was determined by immunostaining of endothelial cells with anti-CD31 monoclonal antibody. Inducible nitric oxide synthase (iNOS) activity and cyclic guanosine monophosphatate (cGMP) levels were assessed in fresh tumor samples, whereas exons 5-9 of the p53 gene were analyzed by reverse transcriptase-polymerase chain reaction, single-strand conformation polymorphism analysis and were sequenced.. MMP-1 overexpression (>10% of tumor cells) was identified in 32 tumors (74.5%), whereas elevated levels of MMP-2 and MMP-9 were detected in 17 tumors (39.5%) each. Tumors with MMP-9 overexpression were characterized by significantly higher MVD (P = 0.05) and significantly higher iNOS activity and cGMP levels (P = 0.005 and P = 0.02, respectively). Moreover, p53 mutation was associated strongly with MMP-9 overexpression (P = 0.004). Conversely, no correlation was found between MMP-1 and MMP-2 expression, angiogenesis, iNOS activity, cGMP levels, and p53 mutation in this series.. This study documents the existence of a correlation between MMP-9 expression, activity of the iNOS pathway, p53 status, and angiogenesis in patients with HNSCC. This raises the possibility that p53 mutation, which frequently is present in HNSCC, may result in increased angiogenesis and invasiveness related to increased nitric oxide and MMP production by tumor cells, ultimately contributing to tumor progression.

Topics: Carcinoma, Squamous Cell; Cyclic GMP; Genes, p53; Head and Neck Neoplasms; Humans; Immunohistochemistry; Laryngeal Neoplasms; Matrix Metalloproteinase 1; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Matrix Metalloproteinases; Microcirculation; Mouth Neoplasms; Mutation; Neovascularization, Pathologic; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Oropharyngeal Neoplasms

Topics: Adult; Aged; Cheek; Cyclic AMP; Cyclic GMP; Facial Neoplasms; Female; Humans; Male; Middle Aged; Mouth Neoplasms

Adenosine and guanosine cyclic monophosphates (cAMP and cGMP) exerted opposite effects at similar concentration and similar effects at markedly different concentrations on the yields of tumors promoted by vitamin A in hamster cheek pouch. Increasing the concentration of cAMP between 10(-5) M and 10(-3) M was associated with increases in tumor yield and diameter which partially or completely overcame the net tumor promotion inhibitory effects which were sometimes seen at 10(-5) M cAMP. In contrast, increasing the concentration of cGMP between 10(-5) M and 10(-3) M caused the net effects to change from increases to decreases in tumor yield without much change in diameter. The relative magnitudes of the tumor yield increasing and decreasing effects of the cyclic nucleotides varied substantially between experiments at constant concentration of cyclic nucleotide. Adenosine-5'-monophosphate (AMP) showed simultaneous tumor promotion inhibitory and growth stimulatory effects, the former effect being similar to that of cAMP but tumor yield decreased rather than increased as concentration of AMP was increased whereas the opposite occured with cAMP. Guanosine-5'-monophosphate (GMP) showed the tumor yield increasing effect of low concentraitons of cGMP but not the yield decreasing effect of high concentrations of cGMP. Adenosine (10(-3) M) showed a significant tumor yield increasing effect similar to that of 10(-3) M cAMP. Guanosine showed no significant effects at either 10(-3) M or 10(-5) M concentrations.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Adenosine; Animals; Carcinoma, Squamous Cell; Cricetinae; Cyclic AMP; Cyclic GMP; Dimethyl Sulfoxide; Female; Guanosine; Mesocricetus; Mouth Neoplasms; Vitamin A

Topics: Animals; Antineoplastic Agents; Antiviral Agents; Arabinonucleotides; Arabinose; Carcinoma; Cell Line; Culture Techniques; Cyclic AMP; Cyclic GMP; HeLa Cells; Herpesviridae; Humans; Laryngeal Neoplasms; Mouth Neoplasms; Phosphoric Diester Hydrolases; Protein Kinases; Sarcoma 180