gastrin-releasing-peptide and Mesothelioma

PET Scans are most often used for detecting cancer and other malignant tumors because for most of them, glucose uptake is higher than in normal tissues. However, in mesothelioma, our study showed excessive deposits of Asbestos of 0.5 mg BDORT units, and markedly reduced Glucose uptake of less than 1/30 of normal tissue. As a consequence, the authors found that, in the location where there is a mesothelioma, distinctive dark black areas much darker than any normal tissue appear in the PET Scan. Therefore, a PET Scan taken parallel to the front & back of the chest wall often shows pitch-black areas on the chest wall of the patient, located on the ribs in the case of large black areas and between the ribs in the case of small black areas. If the amount of Asbestos in these areas is found to be very high in the same location where the glucose uptake is very low, one can suspect the presence of mesothelioma, which is often found at the inner wall of the chest cavity or the peritoneum in the abdomen with significantly increased Osteopontine (about 350-400 times that of normal tissue) and very significant increase in Gastrin Releasing Peptides (more than 1200 times that of normal tissue). In some patients, the only abnormal blood chemistry detected was abnormally increased Pro-Gastrin Releasing Peptide. This dark black area on the PET Scan image taken parallel to front and back of chest wall (with marked increase in asbestos, Gastrin-Releasing Peptide, & Osteopontine and marked decrease in glucose uptake in the pathological tissue) can be considered a characteristic finding for the diagnosis of mesothelioma.

Topics: Aged; Asbestos; Fluorodeoxyglucose F18; Gastrin-Releasing Peptide; Humans; Lung Neoplasms; Male; Mesothelioma; Osteopontin; Positron-Emission Tomography; Radiopharmaceuticals; Thorax

Neutral endopeptidase (NEP; CALLA, CD10, EC 3.4.24.11) is a cell surface endopeptidase that hydrolyses bioactive peptides, including the bombesin-like peptides, as well as other neuropeptides. Bombesin-like peptides and other neuropeptides are autocrine growth factors for both small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). Low expression of NEP has been reported in SCLC and NSCLC cell lines. NEP inhibition has been shown to increase proliferation in one cell line. To date, NEP expression has not been quantitatively evaluated in normal adult lung, SCLC or NSCLC tumors, paired uninvolved lung from the same patient, or in other pulmonary neoplasms such as mesotheliomas and carcinoids. We examined the expression of NEP in these tissues and human cell lines using immunohistochemistry, flow cytometry, enzyme activity, ELISA, Western blot, and reverse transcription (RT)-PCR. Uninvolved lung tissue from different individuals displayed considerable variation in NEP activity and protein. By immunohistochemistry, NEP expression was detectable in alveolar and airway epithelium, fibroblasts of normal lung, and in mesotheliomas, whereas it was undetectable in most SCLC, adenocarcinoma, squamous cell carcinoma, and carcinoid tumors of the lung. NEP activity and protein levels were lower in all SCLC and adenocarcinoma tumors when compared to adjacent uninvolved lung, often at levels consistent with expression derived from contaminating stroma. NEP expression and activity were reduced or undetectable in most SCLC and lung adenocarcinoma cell lines. NEP mRNA by RT-PCR was not expressed or was in low abundance in the majority of lung cancer cell lines. The majority of lung tumors did not express NEP by RT-PCR as compared with normal adjacent lung. In addition, recombinant NEP abolished, whereas an NEP inhibitor potentiated, the calcium flux generated by neuropeptides in some lung cancer cell lines, demonstrating potential physiological significance for low NEP expression. NEP, therefore, is a signal transduction and possibly a growth modulator for both SCLC and NSCLC, emphasizing the role of neuropeptides in the pathogenesis of the major histological forms of lung cancer.

Topics: Adenocarcinoma; Adult; Base Sequence; Blotting, Western; Bradykinin; Calcium; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Cell Line; DNA Primers; Enzyme Inhibitors; Gastrin-Releasing Peptide; Gene Expression; Glycopeptides; Humans; Immunohistochemistry; Lung; Lung Neoplasms; Mesothelioma; Molecular Sequence Data; Neoplasm Metastasis; Neprilysin; Peptides; Polymerase Chain Reaction; Pulmonary Alveoli; Recombinant Proteins; RNA, Messenger; Signal Transduction; Tumor Cells, Cultured