[' ', 'Oo', 'SOS', 'NI', 'eas', 'ee', 'Mae', 'ah', 'ene', 'ROR,', 'PAR', 'oS', 'Sea', 'SEM', 'Sees', '|', 'nevreendocrine', 'cancera.', 'Wa', 'and', 'others', 'showed', 'that', 'the', 'aignal', 'transduction', 'pathway', 'induced', 'by', 'multiple', 'peptides', 'could', 'be', 'blocked', 'by', 'using', 'substance', 'P', 'derivatives', 'which', 'appear', 'to', 'down', 'regulate', 'multiple', 'peptide', 'receptors', 'and', 'by', '6', 'using', 'BS509-035', 'which', 'is', 'a', 'calcium/calmodulin/PKC', 'antagonist.', 'These', '|', 'compounds', 'inhibited', 'the', 'growth', 'of', 'lung', 'cancer', 'cell', 'lines', 'in', 'vitro', 'at', 'concentrations', 'considerably', 'below', 'those', 'which', 'inhibit', 'breast', 'cancer', 'cell', 'i', 'line', 'growth,', 'Ba509-035.', 'was', 'shown', 'to', 'prevent', 'the', 'development', 'of', ')', '“', 'neuroendocrine', 'hyperplasia', 'and', 'neuroendocrine', 'tumors', 'in', 'the', 'Syrian', 'hamater', 'model.', 'It', 'was', 'also', 'shown', 'to', 'be', 'non-toxic', 'in', 'animals', 'and', 'humans.', 'Non-toxic', 'y', 'deses', 'in', 'animals', 'gave', 'concentrations', 'which', 'were', 'well', 'above', 'those', 'which', ':', 'inhibited', 'lung', 'cancer', 'cell', 'line', 'growth', 'in', 'vitro.', 'In', 'this', 'proposal,', 'we', 'wili', 'perform', 'in', 'vitro', 'studies', 'to', 'further', 'elucidate', 'the', 'mechanism', 'of', 'action', 'of', 'these', 'compounds,', 'perform', 'in', 'vivo', 'animal', 'studies', 'to', 'allow', 'these', 'compounds', 'to', 'enter', 'human', 'clinical', 'trials', 'alone', 'and', 'in', 'combination', 'and', 'perform', 'initial', 'phase', 'I', 'and', 'phase', 'II', 'studies', 'in', 'human', 'patients', 'with', 'supportive', 'laboratory', 'evaluations.', '6/7/617', 'DIALOG(R)File', '266:Fed.', 'Res.', 'in', 'Progress', '{c)', 'format', 'only', '1995', 'Dialog', 'Info.Svcs.', 'All', 'rts.', 'reserv.', '0120775', 'IDENTIFYING', 'NO.:', '5P50CA58187-03', '0002', 'AGENCY', 'CODE:', 'CRISP', 'ROLE', 'OF', 'CYCLINS,', 'CDC2/CDC28,', 'CDK2/EG1,', 'AND', 'CDC7', 'PROTEIN', 'KINASES', 'IN', 'LUNG', 'CANCER', 'PRINCIPAL', 'INVESTIGATOR:', 'SCLAFANI,', 'ROBERT', 'A', 'ors', 'UNIV', 'OF', 'COLORADO', 'HLTH', 'SCI', 'CTR', '4200', 'EAST', '9TH', 'AVENUE', 'DENVER,', 'CO', '62', 'PERFORMING', 'ORG.', 'UNIVERSITY', 'OF', 'COLORADO', 'HLTH', 'SCIENCES', 'CTR,', 'DENVER,', 'COLORADO', 'SPONSORING', 'ORG.', 'NATIONAL', 'CANCER', 'INSTITUTE', 'SUMMARY:', 'Cancer', 'may', 'be.', 'the', 'reault', 'of', 'an', 'pnreguiated', 'or', 'poorly', 'regulated', 'prognostic', 'value', 'will', 'be', 'obtained.', 'Overexpression', 'could', 'be', 'used', 'as', 'a', 'marker', 'of', 'this', 'type.', 'As', 'shown', 'from', 'basic', 'research', 'studies', 'on', 'yeast,', 'overexpression', 'of', 'Cdec?', 'kinase', 'atimulates', 'induced', 'mutagenesis.', 'Therefore,', 'kinase', 'oe', 'ok', '’', '3', 'E', '4', '3', '3', '3', '§', '3', 'i', '3', '4', 'normal,', 'dysplastic', '(“premalignant")', 'and', 'malignant', 'lung', 'tissues', 'obtained', 'aan', 'from', '4', 'central', 'tissue', 'bank', 'core.', 'Cyclin', 'proteins', 'which', 'are', 'regulators', 'of', '.', 'these', 'protein', 'kinases', 'will', 'alsc', 'be', 'examined.', 'New', 'lung', 'specific', 'cyclins', 'and', 'and', 'Cde?', 'kinases.', '6/7/618', 'DIALOG(R)', 'File', '266:Fed.', 'Res.', 'in', 'Progress', '(c)', 'format', 'only', '1995', 'Dialog', 'Info.Svcs.', 'All', 'rts.', 'reserv.', 'f~', 'PI6Z', 'OFITS', '~', '—s\\', ' ']