The molecular pathogenesis and management of bronchial carcinoids

Expert Opinion on Therapeutic Targets

Volumn 15, Issue 4, 2011, Pages 457-491

  Cakir, Mehtap ^a   Grossman, Ashley ^b  

^a SELCUK UNIVERSITY   (Turkey)

^b QUEEN MARY UNIVERSITY OF LONDON   (United Kingdom)

Author keywords

Bronchial carcinoid; molecular biology; neuroendocrine tumor; treatment

Indexed keywords

[1,4,7,10 TETRAAZACYCLODODECANE 1,4,7,10 TETRAACETIC ACID] DEXTRO PHE,1 TYR3 OCTREOTATE LU 177; [1,4,7,10 TETRAAZACYCLODODECANE 1,4,7,10 TETRAACETIC ACID] DEXTRO PHE,1 TYR3 OCTREOTATE Y 90; [1,4,7,10 TETRAAZACYCLODODECANE 1,4,7,10 TETRAACETIC ACID] DEXTRO PHE1 TYR3 OCTREOTIDE GA 68; [1,4,7,10 TETRAAZACYCLODODECANE 1,4,7,10 TETRAACETIC ACID] DEXTRO PHE1 TYR3 OCTREOTIDE Y 90; BROMOCRIPTINE; CISPLATIN; COMPLEMENTARY DNA; DACARBAZINE; DICARBOXYPROPANE DIPHOSPHONATE TC 99M; DIHYDROXYPHENYLALANINE F 18; DOTALAN IN 111; DOXORUBICIN; EPIRUBICIN; ETOPOSIDE; FLUORODEOXYGLUCOSE F 18; FLUOROURACIL; HERMES ANTIGEN; IODINE 125; K RAS PROTEIN; MAMMALIAN TARGET OF RAPAMYCIN; OXALIPLATIN; PENTETREOTIDE IN 111; PLATELET DERIVED GROWTH FACTOR RECEPTOR; RADIOISOTOPE; RADIOPHARMACEUTICAL AGENT; SOMATOMEDIN C RECEPTOR; TRANSFORMING GROWTH FACTOR BETA; TRANSFORMING GROWTH FACTOR BETA1; TYROSINE 3 OCTREOTIDE IN 111; UNCLASSIFIED DRUG; UNINDEXED DRUG;

AUTORADIOGRAPHY; BRONCHUS CARCINOID; CANCER CELL CULTURE; CHROMOSOME 10Q; CHROMOSOME 11Q; CHROMOSOME 13Q; CHROMOSOME 17Q; CHROMOSOME 19; CHROMOSOME 3P; COMPARATIVE GENOMIC HYBRIDIZATION; DRUG TARGETING; GENE DELETION; GENE DOSAGE; GENE EXPRESSION; HETEROZYGOSITY LOSS; HUMAN; IMMUNOHISTOCHEMISTRY; MEDLINE; MICROARRAY ANALYSIS; MICROSATELLITE MARKER; MOLECULAR BIOLOGY; MOLECULAR PATHOLOGY; NEUROENDOCRINE TUMOR; POINT MUTATION; POLYMERASE CHAIN REACTION; PROMOTER REGION; REVIEW; SIGNAL TRANSDUCTION;

ANTINEOPLASTIC AGENTS; BRONCHIAL NEOPLASMS; CARCINOID TUMOR; CARCINOMA, NEUROENDOCRINE; CARCINOMA, SMALL CELL; HUMANS; LUNG; LUNG NEOPLASMS; MOLECULAR TARGETED THERAPY; NEUROENDOCRINE TUMORS; SIGNAL TRANSDUCTION; SMALL CELL LUNG CARCINOMA;

EID: 79952660502     PISSN: 14728222     EISSN: None     Source Type: Journal    
DOI: 10.1517/14728222.2011.555403     Document Type: Review

References (262)

1. Eriksson B, Oberg K. Carcinoid syndrome. In: Jameson JL, De Groot LJ, editors, Endocrinology. Saunders Elsevier, Philadelphia, PA; 2010. p. 2774-86
2. Leotlela PD, Jauch A, Holtgreve-Grez H, et al. Genetics of neuroendocrine and carcinoid tumours. Endocr Relat Cancer 2003;10:437-50 (Pubitemid 38094880)
3. Oberg K. Carcinoid tumors: molecular genetics, tumor biology, and update of diagnosis and treatment. Curr Opin Oncol 2002;14:38-45 (Pubitemid 34072962)
4. Travis WD. Lung tumours with neuroendocrine differentiation. Eur J Cancer 2009;45(Suppl 1):251-66
5. Travis WD, Colby TV, Corrin B, et al. The spectrum of neuroendocrine tumours. In: Sobin LH, editor, WHO International histological classification of tumours. Histological typing of lung and pleural tumours. Springer-Verlag, Berlin; 1999. p. 7-9
6. Phan AT, Oberg K, Choi J, et al. NANETS consensus guideline for the diagnosis and management of neuroendocrine tumors: well-differentiated neuroendocrine tumors of the thorax (includes lung and thymus). Pancreas 2010;39:784-98
7. Moran CA, Suster S. Neuroendocrine carcinomas (carcinoid, atypical carcinoid, small cell carcinoma, and large cell neuroendocrine carcinoma): current concepts. Hematol Oncol Clin North Am 2007;21:395-407 (Pubitemid 46843517)
8. Bertino EM, Confer PD, Colonna JE, et al. Pulmonary neuroendocrine/ carcinoid tumors: a review article. Cancer 2009;115:4434-41
9. Travis WD, Brambilla E, Muller-Hermelink HK, Harris CC. Pathology and genetics: tumours of the lung, pleura, thymus and heart. IARC, Lyon; 2004
10. Siddiqui MT. Pulmonary neuroendocrine neoplasms: a review of clinicopathologic and cytologic features. Diagn Cytopathol 2010;38:607-17
11. Gustafsson BI, Kidd M, Chan A, et al. Bronchopulmonary neuroendocrine tumors. Cancer 2008;113:5-21 (Pubitemid 351976381)
12. Modlin IM, Lye KD, Kidd M. A 5-decade analysis of 13,715 carcinoid tumors. Cancer 2003;97:934-59 (Pubitemid 36173145)
13. Marx SJ. Molecular genetics of multiple endocrine neoplasia types 1 and 2. Nat Rev Cancer 2005;5:367-75 (Pubitemid 40637828)
14. Sachithanandan N, Harle RA, Burgess JR. Bronchopulmonary carcinoid in multiple endocrine neoplasia type 1. Cancer 2005;103:509-15
15. Demay RM. Lung. In: Demay RM, editor, The art and science of cytopathology. American Society of Clinical Pathologists Press, Chicago, IL; 1996. p. 947-98
16. Davies SJ, Gosney JR, Hansell DM, et al. Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia: an under-recognized spectrum of disease. Thorax 2007;62:248-52 (Pubitemid 46579807)
17. Skov BG, Krasnik M, Lantuejoul S, et al. Reclassification of neuroendocrine tumors improves the separation of carcinoids and the prediction of survival. J Thorac Oncol 2008;3:1410-15
18. Fathi Z, Corjay MH, Shapira H, et al. BRS-3: a novel bombesin receptor subtype selectively expressed in testis and lung carcinoma cells. J Biol Chem 1993;268:5979-84 (Pubitemid 23090935)
19. Moody TW, Zia F, Venugopal R, et al. GRP receptors are present in non small cell lung cancer cells. J Cell Biochem Suppl 1996;24:247-56
20. Ryan RR, Weber HC, Mantey SA, et al. Pharmacology and intracellular signaling mechanisms of the native human orphan receptor BRS-3 in lung cancer cells. J Pharmacol Exp Ther 1998;287:366-80 (Pubitemid 29140222)
21. Lai SL, Perng RP, Hwang J. p53 gene status modulates the chemosensitivity of non-small cell lung cancer cells. J Biomed Sci 2000;7:64-70 (Pubitemid 30046573)
22. Kazanjian A, Wallis D, Au N, et al. Growth factor independence-1 is expressed in primary human neuroendocrine lung carcinomas and mediates the differentiation of murine pulmonary neuroendocrine cells. Cancer Res 2004;64:6874-82 (Pubitemid 39330994)
23. Kunnimalaiyaan M, Yan S, Wong F, et al. Hairy Enhancer of Split-1 (HES-1), a Notch1 effector, inhibits the growth of carcinoid tumor cells. Surgery 2005;138:1137-42 (Pubitemid 41797355)
24. Plummer HK III, Dhar M, Schuller HM. Expression of the alpha7 nicotinic acetylcholine receptor in human lung cells. Respir Res 2005;6:29
25. Plummer HK III, Dhar MS, Cekanova M, et al. Expression of G-protein inwardly rectifying potassium channels (GIRKs) in lung cancer cell lines. BMC Cancer 2005;5:104
26. Ahmed AU, Schmidt RL, Park CH, et al. Effect of disrupting seven-in-absentia homolog 2 function on lung cancer cell growth. J Natl Cancer Inst 2008;100:1606-29
27. Castano Z, Vergara-Irigaray N, Pajares MJ, et al. Expression of alpha CP-4 inhibits cell cycle progression and suppresses tumorigenicity of lung cancer cells. Int J Cancer 2008;122:1512-20 (Pubitemid 351294959)
28. Pitt SC, Chen H, Kunnimalaiyaan M. Phosphatidylinositol 3-kinase-Akt signaling in pulmonary carcinoid cells. J Am Coll Surg 2009;209:82-8
29. Stepien T, Sacewicz M, Lawnicka H, et al. Stimulatory effect of growth hormone-releasing hormone (GHRH(1-29)NH2) on the proliferation, VEGF and chromogranin A secretion by human neuroendocrine tumor cell line NCI-H727 in vitro. Neuropeptides 2009;43:397-400
30. Cortes-Sempere M, Chattopadhyay S, Rovira A, et al. MKP1 repression is required for the chemosensitizing effects of NFkappaB and PI3K inhibitors to cisplatin in non-small cell lung cancer. Cancer Lett 2009;286:206-16
31. Rickman OB, Vohra PK, Sanyal B, et al. Analysis of ErbB receptors in pulmonary carcinoid tumors. Clin Cancer Res 2009;15:3315-24
32. Gilbert JA, Adhikari LJ, Lloyd RV, et al. Molecular markers for novel therapies inneuroendocrine (carcinoid) tumors. Endocr Relat Cancer 2010;17:623-36
33. Haley SA, OHara BA, Banerjee R, et al. Unique susceptibility of a human lung carcinoid tumor cell line to infection with BK virus. Virus Res 2010;149:128-32
34. Svejda B, Kidd M, Giovinazzo F, et al. The 5-HT(2B) receptor plays a key regulatory role in both neuroendocrine tumor cell proliferation and the modulation of the fibroblast component of the neoplastic microenvironment. Cancer 2010;116:2902-12
35. Srirajaskanthan R, Caplin ME, Waugh MG, et al. Identification of Mac-2-binding protein as a putative marker of neuroendocrine tumors from the analysis of cell line secretomes. Mol Cell Proteomics 2010;9:656-66
36. Kunnimalaiyaan M, Chen H. Tumor suppressor role of Notch-1 signaling in neuroendocrine tumors. Oncologist 2007;12:535-42 (Pubitemid 350012116)
37. Jakobovitz O, Nass D, DeMarco L, et al. Carcinoid tumors frequently display genetic abnormalities involving chromosome 11. J Clin Endocrinol Metab 1996;81:3164-7 (Pubitemid 26296181)
38. Debelenko LV, Brambilla E, Agarwal SK, et al. Identification of MEN1 gene mutations in sporadic carcinoid tumors of the lung. Hum Mol Genet 1997;6:2285-90 (Pubitemid 27501081)
39. Onuki N, Wistuba II, Travis WD, et al. Genetic changes in the spectrum of neuroendocrine lung tumors. Cancer 1999;85:600-7 (Pubitemid 29075281)
40. Finkelstein SD, Hasegawa T, Colby T, et al. 11q13 allelic imbalance discriminates pulmonary carcinoids from tumorlets. A microdissection-based genotyping approach useful in clinical practice. Am J Pathol 1999;155:633-40 (Pubitemid 29370413)
41. Vageli D, Daniil Z, Dahabreh J, et al. Microsatellite instability and loss of heterozygosity at the MEN1 locus in lung carcinoid tumors: a novel approach using real-time PCR with melting curve analysis in histopathologic material. Oncol Rep 2006;15:557-64
42. Petzmann S, Ullmann R, Klemen H, et al. Loss of heterozygosity on chromosome arm 11q in lung carcinoids. Hum Pathol 2001;32:333-8 (Pubitemid 32246809)
43. Gortz B, Roth J, Krahenmann A, et al. Mutations and allelic deletions of the MEN1 gene are associated with a subset of sporadic endocrine pancreatic and neuroendocrine tumors and not restricted to foregut neoplasms. Am J Pathol 1999;154:429-36 (Pubitemid 29094093)
44. Hurr K, Kemp B, Silver SA, et al. Microsatellite alteration at chromosome 3p loci in neuroendocrine and non-neuroendocrine lung tumors. Histogenetic and clinical relevance. Am J Pathol 1996;149:613-20 (Pubitemid 26256348)
45. Kovatich A, Friedland DM, Druck T, et al. Molecular alterations to human chromosome 3p loci in neuroendocrine lung tumors. Cancer 1998;83:1109-17 (Pubitemid 28419063)
46. Sugio K, Osaki T, Oyama T, et al. Genetic alteration in carcinoid tumors of the lung. Ann Thorac Cardiovasc Surg 2003;9:149-54
47. Kobayashi Y, Tokuchi Y, Hashimoto T, et al. Molecular markers for reinforcement of histological subclassification of neuroendocrine lung tumors. Cancer Sci 2004;95:334-41 (Pubitemid 38519474)
48. Pearce SH, Trump D, Wooding C, et al. Loss of heterozygosity studies at the retinoblastoma and breast cancer susceptibility (BRCA2) loci in pituitary, parathyroid, pancreatic and carcinoid tumours. Clin Endocrinol (Oxf ) 1996;45:195-200 (Pubitemid 26278313)
49. DAdda T, Bottarelli L, Azzoni C, et al. Malignancy-associated X chromosome allelic losses in foregut endocrine neoplasms: further evidence from lung tumors. Mod Pathol 2005;18:795-805 (Pubitemid 40780513)
50. DAlessandro V, Muscarella LA, la Torre A, et al. Molecular analysis of the HuD gene in neuroendocrine lung cancers. Lung Cancer 2010;67:69-75
51. Walch AK, Zitzelsberger HF, Aubele MM, et al. Typical and atypical carcinoid tumors of the lung are characterized by 11q deletions as detected by comparative genomic hybridization. Am J Pathol 1998;153:1089-98 (Pubitemid 28465832)
52. Ullmann R, Petzmann S, Klemen H, et al. The position of pulmonary carcinoids within the spectrum of neuroendocrine tumors of the lung and other tissues. Genes Chromosomes Cancer 2002;34:78-85 (Pubitemid 34260599)
53. Zhao J, de Krijger RR, Meier D, et al. Genomic alterations in well-differentiated gastrointestinal and bronchial neuroendocrine tumors (carcinoids): marked differences indicating diversity in molecular pathogenesis. Am J Pathol 2000;157:1431-38
54. Petzmann S, Ullmann R, Halbwedl I, et al. Analysis of chromosome-11 aberrations in pulmonary and gastrointestinal carcinoids: an array comparative genomic hybridization-based study. Virchows Arch 2004;445:151-9 (Pubitemid 39215546)
55. Warth A, Herpel E, Krysa S, et al. Chromosomal instability is more frequent in metastasized than in non-metastasized pulmonary carcinoids but is not a reliable predictor of metastatic potential. Exp Mol Med 2009;41:349-53
56. Voortman J, Lee JH, Killian JK, et al. Array comparative genomic hybridization-based characterization of genetic alterations in pulmonary neuroendocrine tumors. Proc Natl Acad Sci USA 2010;107:13040-5
57. Couce ME, Bautista D, Costa J, et al. Analysis of K-ras, N-ras, H-ras, and p53 in lung neuroendocrine neoplasms. Diagn Mol Pathol 1999;8:71-9 (Pubitemid 29399036)
58. Lohmann DR, Fesseler B, Putz B, et al. Infrequent mutations of the p53 gene in pulmonary carcinoid tumors. Cancer Res 1993;53:5797-801 (Pubitemid 23360290)
59. Przygodzki RM, Finkelstein SD, Langer JC, et al. Analysis of p53, K-ras-2, and C-raf-1 in pulmonary neuroendocrine tumors. Correlation with histological subtype and clinical outcome. Am J Pathol 1996;148:1531-41
60. Perren A, Schmid S, Locher T, et al. BRAF and endocrine tumors: mutations are frequent in papillary thyroid carcinomas, rare in endocrine tumors of the gastrointestinal tract and not detected in other endocrine tumors. Endocr Relat Cancer 2004;11:855-60 (Pubitemid 40065557)
61. Dong Q, Debelenko LV, Chandrasekharappa SC, et al. Loss of heterozygosity at 11q13: analysis of pituitary tumors, lung carcinoids, lipomas, and other uncommon tumors in subjects with familial multiple endocrine neoplasia type 1. J Clin Endocrinol Metab 1997;82:1416-20 (Pubitemid 27200411)
62. Oliveira AM, Tazelaar HD, Wentzlaff KA, et al. Familial pulmonary carcinoid tumors. Cancer 2001;91:2104-9 (Pubitemid 32476375)
63. Toyooka S, Toyooka KO, Maruyama R, et al. DNA methylation profiles of lung tumors. Mol Cancer Ther 2001;1:61-7
64. Shivapurkar N, Toyooka S, Eby MT, et al. Differential inactivation of caspase-8 in lung cancers. Cancer Biol Ther 2002;1:65-169
65. Sathyanarayana UG, Toyooka S, Padar A, et al. Epigenetic inactivation of laminin-5-encoding genes in lung cancers. Clin Cancer Res 2003;9:2665-7
66. Momparler RL, Eliopoulos N, Ayoub J. Evaluation of an inhibitor of DNA methylation, 5-aza-2ó-deoxycytidine, for the treatment of lung cancer and the future role of gene therapy. Adv Exp Med Biol 2000;465:433-46 (Pubitemid 32193354)
67. Bhattacharjee A, Richards WG, Staunton J, et al. Classification of human lung carcinomas by mRNA expression profiling reveals distinct adenocarcinoma subclasses. Proc Natl Acad Sci USA 2001;98:13790-5 (Pubitemid 33115977)
68. He P, Varticovski L, Bowman ED, et al. Identification of carboxypeptidase E and gamma-glutamyl hydrolase as biomarkers for pulmonary neuroendocrine tumors by cDNA microarray. Hum Pathol 2004;35:1196-209 (Pubitemid 39361642)
69. Kim do H, Nagano Y, Choi IS, et al. Allelic alterations in well-differentiated neuroendocrine tumors (carcinoid tumors) identified by genome-wide single nucleotide polymorphism analysis and comparison with pancreatic endocrine tumors. Genes Chromosomes Cancer 2008;47:84-92 (Pubitemid 350191467)
70. Morandi U, Casali C, Rossi G. Bronchial typical carcinoid tumors. Semin Thorac Cardiovasc Surg 2006;18:191-8 (Pubitemid 44914572)
71. Reubi JC, Kappeler A, Waser B, et al. Immunohistochemical localization of somatostatin receptors sst2A in human tumors. Am J Pathol 1998;153:233-45 (Pubitemid 28317526)
72. Papotti M, Croce S, Macri L, et al. Correlative immunohistochemical and reverse transcriptase polymerase chain reaction analysis of somatostatin receptor type 2 in neuroendocrine tumors of the lung. Diagn Mol Pathol 2000;9:47-57 (Pubitemid 30131962)
73. Papotti M, Croce S, Bello M, et al. Expression of somatostatin receptor types 2, 3 and 5 in biopsies and surgical specimens of human lung tumours. Correlation with preoperative octreotide scintigraphy. Virchows Arch 2001;439:787-97 (Pubitemid 33141324)
74. Righi L, Volante M, Tavaglione V, et al. Somatostatin receptor tissue distribution in lung neuroendocrine tumours: a clinicopathologic and immunohistochemical study of 218 clinically aggressive cases. Ann Oncol 2010;21:548-55
75. Pivonello R, Ferone D, de Herder WW, et al. Dopamine receptor expression and function in corticotroph ectopic tumors. J Clin Endocrinol Metab 2007;92:65-9 (Pubitemid 46067510)
76. Grossrubatscher E, Veronese S, Ciaramella PD, et al. High expression of dopamine receptor subtype 2 in a large series of neuroendocrine tumors. Cancer Biol Ther 2008;7:1970-8
77. Sica G, Wagner PL, Altorki N, et al. Immunohistochemical expression of estrogen and progesterone receptors in primary pulmonary neuroendocrine tumors. Arch Pathol Lab Med 2008;132:1889-95
78. Brambilla E, Constantin B, Drabkin H, et al. Semaphorin SEMA3F localization in malignant human lung and cell lines: a suggested role in cell adhesion and cell migration. Am J Pathol 2000;156:939-50 (Pubitemid 30626952)
79. Lantuejoul S, Constantin B, Drabkin H, et al. Expression of VEGF, semaphoring SEMA3F, and their common receptors neuropilins NP1 and NP2 in preinvasive bronchial lesions, lung tumours, and cell lines. J Pathol 2003;200:336-47 (Pubitemid 36827308)
80. Wilkinson N, Hasleton PS, Wilkes S, et al. Lack of C-erbB-2 protein expression in pulmonary carcinoid tumours. J Clin Pathol 1991;44:343
81. Granberg D, Wilander E, Oberg K. Expression of tyrosine kinase receptors in lung carcinoids. Tumour Biol 2006;27:153-7
82. Roncalli M, Doglioni C, Springall DR, et al. Abnormal p53 expression in lung neuroendocrine tumors. Diagnostic and prognostic implications. Diagn Mol Pathol 1992;1:129-35
83. Barbareschi M, Girlando S, Mauri FA, et al. Tumour suppressor gene products, proliferation, and differentiation markers in lung neuroendocrine neoplasms. J Pathol 1992;166:343-50
84. Wang BY, Gil J, Kaufman D, et al. P63 in pulmonary epithelium, pulmonary squamous neoplasms, and other pulmonary tumors. Hum Pathol 2002;33:921-6
85. Au NH, Gown AM, Cheang M, et al. P63 expression in lung carcinoma: a tissue microarray study of 408 cases. Appl Immunohistochem Mol Morphol 2004;12:240-7
86. Rusch VW, Klimstra DS, Venkatraman ES. Molecular markers help characterize neuroendocrine lung tumors. Ann Thorac Surg 1996;62:798-809
87. Brambilla E, Negoescu A, Gazzeri S, et al. Apoptosis-related factors p53, Bcl2, and Bax in neuroendocrine lung tumors. Am J Pathol 1996;149:1941-52 (Pubitemid 26415213)
88. Coppola D, Clarke M, Landreneau R, et al. Bcl-2, p53, CD44, and CD44v6 isoform expression in neuroendocrine tumors of the lung. Mod Pathol 1996;9:484-90 (Pubitemid 26171662)
89. Wang DG, Johnston CF, Sloan JM, et al. Expression of Bcl-2 in lung neuroendocrine tumours: comparison with p53. J Pathol 1998;184:247-51 (Pubitemid 28112779)
90. Zirbes TK, Lorenzen J, Baldus SE, et al. Apoptosis and expression of bcl-2 protein are inverse factors influencing tumour cell turnover in primary carcinoid tumours of the lung. Histopathology 1998;33:123-8 (Pubitemid 28387021)
91. Laitinen KL, Soini Y, Mattila J, et al. Atypical bronchopulmonary carcinoids show a tendency toward increased apoptotic and proliferative activity. Cancer 2000;88:1590-8 (Pubitemid 30183144)
92. LaPoint RJ, Bourne PA, Wang HL, et al. Coexpression of c-kit and bcl-2 in small cell carcinoma and large cell neuroendocrine carcinoma of the lung. Appl Immunohistochem Mol Morphol 2007;15:401-6 (Pubitemid 350307845)
93. Cagle PT, el-Naggar AK, Xu HJ, et al. Differential retinoblastoma protein expression in neuroendocrine tumors of the lung. Potential diagnostic implications. Am J Pathol 1997;150:393-400 (Pubitemid 27073768)
94. Gouyer V, Gazzeri S, Bolon I, et al. Mechanism of retinoblastoma gene inactivation in the spectrum of neuroendocrine lung tumors. Am J Respir Cell Mol Biol 1998;18:188-96 (Pubitemid 128355192)
95. Dosaka-Akita H, Cagle PT, Hiroumi H, et al. Differential retinoblastoma and p16 (INK4A) protein expression in neuroendocrine tumors of the lung. Cancer 2000;88:550-6 (Pubitemid 30056928)
96. Beasley MB, Lantuejoul S, Abbondanzo S, et al. The P16/cyclin D1/Rb pathway in neuroendocrine tumors of the lung. Hum Pathol 2003;34:136-42 (Pubitemid 36258804)
97. Igarashi T, Jiang SX, Kameya T, et al. Divergent cyclin B1 expression and Rb/p16/cyclin D1 pathway aberrations among pulmonary neuroendocrine tumors. Mod Pathol 2004;17:1259-67 (Pubitemid 39312952)
98. Sarvesvaran J, Going JJ, Milroy R, et al. Is small cell lung cancer the perfect target for anti-telomerase treatment? Carcinogenesis 1999;20:1649-51 (Pubitemid 29385461)
99. Zaffaroni N, De Polo D, Villa R, et al. Differential expression of telomerase activity in neuroendocrine lung tumours: correlation with gene product immunophenotyping. J Pathol 2003;201:127-33 (Pubitemid 37121211)
100. Zaffaroni N, Villa R, Pastorino U, et al. Lack of telomerase activity in lung carcinoids is dependent on human telomerase reverse transcriptase transcription and alternative splicing and is associated with long telomeres. Clin Cancer Res 2005;11:2832-9 (Pubitemid 40525181)
101. Nishio Y, Nakanishi K, Ozeki Y, et al. Telomere length, telomerase activity, and expressions of human telomerase mRNA component (hTERC) and human telomerase reverse transcriptase (hTERT) mRNA in pulmonary neuroendocrine tumors. Jpn J Clin Oncol 2007;37:16-22 (Pubitemid 47090719)
102. Clavel CE, Nollet F, Berx G, et al. Expression of the E-cadherin-catenin complex in lung neuroendocrine tumours. J Pathol 2001;194:20-6
103. Salon C, Moro D, Lantuejoul S, et al. E-cadherin-beta-catenin adhesion complex in neuroendocrine tumors of the lung: a suggested role upon local invasion and metastasis. Hum Pathol 2004;35:1148-55 (Pubitemid 39165348)
104. Pelosi G, Scarpa A, Puppa G, et al. Alteration of the E-cadherin/beta-catenin cell adhesion system is common in pulmonary neuroendocrine tumors and is an independent predictor of lymph node metastasis in atypical carcinoids. Cancer 2005;103:1154-64 (Pubitemid 40328085)
105. Galvan JA, Gonzalez MV, Crespo G, et al. Snail nuclear expression parallels higher malignancy potential in neuroendocrine lung tumors. Lung Cancer 2010;69:289-95
106. Pelosi G, Pasini F, Fraggetta F, et al. Independent value of fascin immunoreactivity for predicting lymph node metastases in typical and atypical pulmonary carcinoids. Lung Cancer 2003;42:203-13 (Pubitemid 37268031)
107. Fabbro D, Di Loreto C, Stamerra O, et al. TTF-1 gene expression in human lung tumours. Eur J Cancer 1996;32A:512-17
108. Folpe AL, Gown AM, Lamps LW, et al. Thyroid transcription factor-1: immunohistochemical evaluation in pulmonary neuroendocrine tumors. Mod Pathol 1999;12:5-8 (Pubitemid 29059159)
109. Kaufmann O, Dietel M. Expression of thyroid transcription factor-1 in pulmonary and extrapulmonary small cell carcinomas and other neuroendocrine carcinomas of various primary sites. Histopathology 2000;36:415-20 (Pubitemid 30311623)
110. Oliveira AM, Tazelaar HD, Myers JL, et al. Thyroid transcription factor-1 distinguishes metastatic pulmonary from well-differentiated neuroendocrine tumors of other sites. Am J Surg Pathol 2001;25:815-19 (Pubitemid 32496873)
111. Sturm N, Rossi G, Lantuejoul S, et al. Expression of thyroid transcription factor-1 in the spectrum of neuroendocrine cell lung proliferations with special interest in carcinoids. Hum Pathol 2002;33:175-82 (Pubitemid 34298732)
112. Du EZ, Goldstraw P, Zacharias J, et al. TTF-1 expression is specific for lung primary in typical and atypical carcinoids: TTF-1-positive carcinoids are predominantly in peripheral location. Hum Pathol 2004;35:825-31 (Pubitemid 38903075)
113. Saqi A, Alexis D, Remotti F, et al. Usefulness of CDX2 and TTF-1 in differentiating gastrointestinal from pulmonary carcinoids. Am J Clin Pathol 2005;123:394-404 (Pubitemid 40315081)
114. Lin X, Saad RS, Luckasevic TM, et al. Diagnostic value of CDX-2 and TTF-1 expressions in separating metastatic neuroendocrine neoplasms of unknown origin. Appl Immunohistochem Mol Morphol 2007;15:407-14 (Pubitemid 350307846)
115. Moskaluk CA, Zhang H, Powell SM, et al. Cdx2 protein expression in normal and malignant human tissues: an immunohistochemical survey using tissue microarrays. Mod Pathol 2003;16:913-19 (Pubitemid 37152021)
116. Jaffee IM, Rahmani M, Singhal MG, et al. Expression of the intestinal transcription factor CDX2 in carcinoid tumors is a marker of midgut origin. Arch Pathol Lab Med 2006;130:1522-6 (Pubitemid 44520720)
117. Matoso A, Singh K, Jacob R, et al. Comparison of thyroid transcription factor-1 expression by 2 monoclonal antibodies in pulmonary and nonpulmonary primary tumors. Appl Immunohistochem Mol Morphol 2010;18:142-9
118. Khoor A, Stahlman MT, Johnson JM, et al. Forkhead box A2 transcription factor is expressed in all types of neuroendocrine lung tumors. Hum Pathol 2004;35:560-4 (Pubitemid 38656939)
119. Chu P, Wu E, Weiss LM. Cytokeratin 7 and cytokeratin 20 expression in epithelial neoplasms: a survey of 435 cases. Mod Pathol 2000;13:962-72
120. Cai YC, Banner B, Glickman J, et al. Cytokeratin 7 and 20 and thyroid transcription factor 1 can help distinguish pulmonary from gastrointestinal carcinoid and pancreatic endocrine tumors. Hum Pathol 2001;32:1087-93 (Pubitemid 33015669)
121. Srivastava A, Hornick JL. Immunohistochemical staining for CDX-2, PDX-1, NESP-55, and TTF-1 can help distinguish gastrointestinal carcinoid tumors from pancreatic endocrine and pulmonary carcinoid tumors. Am J Surg Pathol 2009;33:626-32
122. Salon C, Merdzhanova G, Brambilla C, et al. E2F-1, Skp2 and cyclin E oncoproteins are upregulated and directly correlated in high-grade neuroendocrine lung tumors. Oncogene 2007;26:6927-36 (Pubitemid 47609079)
123. Salon C, Brambilla E, Brambilla C, et al. Altered pattern of Cul-1 protein expression and neddylation in human lung tumours: relationships with CAND1 and cyclin E protein levels. J Pathol 2007;213:303-10 (Pubitemid 350074020)
124. Jiang SX, Kameya T, Asamura H, et al. hASH1 expression is closely correlated with endocrine phenotype and differentiation extent in pulmonary neuroendocrine tumors. Mod Pathol 2004;17:222-9 (Pubitemid 41656519)
125. Granberg D, Skogseid B, Welin S, et al. Gastrin-releasing-peptide in neuroendorine tumours. Acta Oncol 2006;45:23-7 (Pubitemid 43214638)
126. Wang LJ, Greaves WO, Sabo E, et al. GCDFP-15 positive and TTF-1 negative primary lung neoplasms: a tissue microarray study of 381 primary lung tumors. Appl Immunohistochem Mol Morphol 2009;17:505-11
127. Senden NH, Timmer ED, de Bruine A, et al. A comparison of NSP-reticulons with conventional neuroendocrine markers in immunophenotyping of lung cancers. J Pathol 1997;182:13-21 (Pubitemid 27240444)
128. Arbiser ZK, Arbiser JL, Cohen C, et al. Neuroendocrine lung tumors: grade correlates with proliferation but not angiogenesis. Mod Pathol 2001;14:1195-9 (Pubitemid 33151160)
129. Katsetos CD, Kontogeorgos G, Geddes JF, et al. Differential distribution of the neuron-associated class III beta-tubulin in neuroendocrine lung tumors. Arch Pathol Lab Med 2000;124:535-44 (Pubitemid 30210985)
130. Liu Y, Sturgis CD, Grzybicki DM, et al. Microtubule-associated protein-2: a new sensitive and specific marker for pulmonary carcinoid tumor and small cell carcinoma. Mod Pathol 2001;14:880-5 (Pubitemid 32889246)
131. Sturm N, Rossi G, Lantuejoul S, et al. 34betaE12 expression along the whole spectrum of neuroendocrine proliferations of the lung, from neuroendocrine cell hyperplasia to small cell carcinoma. Histopathology 2003;42:156-66 (Pubitemid 36237848)
132. Ricci A, Graziano P, Mariotta S, et al. Neurotrophin system expression in human pulmonary carcinoid tumors. Growth Factors 2005;23:303-12 (Pubitemid 43123827)
133. Cooper CS, Nicholson AG, Foster C, et al. Nuclear overexpression of the E2F3 transcription factor in human lung cancer. Lung Cancer 2006;54:155-62 (Pubitemid 44764914)
134. Johnson KR, Johnson KY, Crellin HG, et al. Immunohistochemical distribution of sphingosine kinase 1 in normal and tumor lung tissue. J Histochem Cytochem 2005;53:1159-66 (Pubitemid 41262984)
135. Lai M, Lu B, Xing X, et al. Secretagogin, a novel neuroendocrine marker, has a distinct expression pattern from chromogranin A. Virchows Arch 2006;449:402-9 (Pubitemid 44451314)
136. Rumilla KM, Erickson LA, Erickson AK, et al. Galectin-4 expression in carcinoid tumors. Endocr Pathol 2006;17:243-9
137. Pelosi G, Leon ME, Veronesi G, et al. Decreased immunoreactivity of CD99 is an independent predictor of regional lymph node metastases in pulmonary carcinoid tumors. J Thorac Oncol 2006;1:468-77 (Pubitemid 47181425)
138. Xu H, Bourne PA, Spaulding BO, et al. High-grade neuroendocrine carcinomas of the lung express K homology domain containing protein overexpressed in cancer but carcinoid tumors do not. Hum Pathol 2007;38:555-63 (Pubitemid 46399894)
139. Shilo K, Dracheva T, Mani H, et al. Alpha-methylacyl CoA racemase in pulmonary adenocarcinoma, squamous cell carcinoma, and neuroendocrine tumors: expression and survival analysis. Arch Pathol Lab Med 2007;131:1555-60 (Pubitemid 47606721)
140. Moldvay J, Jackel M, Paska C, et al. Distinct claudin expression profile in histologic subtypes of lung cancer. Lung Cancer 2007;57:159-67 (Pubitemid 47043180)
141. Kasprzak A, Olejniczak K, Przybyszewska W, et al. Cellular expression of interleukin 2 (IL-2) and its receptor (IL-2R, CD25) in lung tumours. Folia Morphol (Warsz) 2007;66:159-66 (Pubitemid 47422713)
142. Kaira K, Oriuchi N, Imai H, et al. Expression of L-type amino acid transporter 1 (LAT1) in neuroendocrine tumors of the lung. Pathol Res Pract 2008;204:553-61
143. Amin RM, Hiroshima K, Iyoda A, et al. LKB1 protein expression in neuroendocrine tumors of the lung. Pathol Int 2008;58:84-8
144. Ceppi P, Volante M, Ferrero A, et al. Thymidylate synthase expression in gastroenteropancreatic and pulmonary neuroendocrine tumors. Clin Cancer Res 2008;14:1059-64 (Pubitemid 351302551)
145. Kim HS, Yi SY, Jun HJ, et al. L1 cell adhesion molecule as a predictor for recurrence in pulmonary carcinoids and large-cell neuroendocrine tumors. APMIS 2009;117:140-6
146. Ozbudak IH, Shilo K, Tavora F, et al. Glucose transporter-1 in pulmonary neuroendocrine carcinomas: expression and survival analysis. Mod Pathol 2009;22:633-8
147. Shimakage M, Kodama K, Kawahara K, et al. Downregulation of drs tumor suppressor gene in highly malignant human pulmonary neuroendocrine tumors. Oncol Rep 2009;21:1367-72
148. Kanteti R, Nallasura V, Loganathan S, et al. PAX5 is expressed in small-cell lung cancer and positively regulates c-Met transcription. Lab Invest 2009;89:301-14
149. Skov BG, Holm B, Erreboe A, et al. ERCC1 and Ki67 in small cell lung carcinoma and other neuroendocrine tumors of the lung: distribution and impact on survival. J Thorac Oncol 2010;5:453-9
150. Fasano M, Sabatini MT, Wieczorek R, et al. CD44 and its v6 spliced variant in lung tumors: a role in histogenesis? Cancer 1997;80:34-41 (Pubitemid 27270917)
151. Granberg D, Wilander E, Oberg K, et al. Decreased survival in patients with CD44-negative typical bronchial carcinoid tumors. Int J Cancer 1999;84:484-88
152. Erasmus JJ, McAdams HP, Patz EF Jr, et al. Evaluation of primary pulmonary carcinoid tumors using FDG PET. AJR Am J Roentgenol 1998;170:1369-73 (Pubitemid 28210961)
153. Pasquali C, Rubello D, Sperti C, et al. Neuroendocrine tumor imaging: can 18F-fluorodeoxyglucose positron emission tomography detect tumors with poor prognosis and aggressive behavior? World J Surg 1998;22:588-92 (Pubitemid 28215437)
154. Traub T, Petkov V, Ofluoglu S, et al. 111In-DOTA-lanreotide scintigraphy in patients with tumors of the lung. J Nucl Med 2001;42:1309-15 (Pubitemid 32852604)
155. Hofmann M, Maecke H, Borner R, et al. Biokinetics and imaging with the somatostatin receptor PET radioligand 68Ga-DOTATOC: preliminary data. Eur J Nucl Med 2001;28:1751-7
156. Belhocine T, Foidart J, Rigo P, et al. Fluorodeoxyglucose positron emission tomography and somatostatin receptor scintigraphy for diagnosing and staging carcinoid tumours: correlations with the pathological indexes p53 and Ki-67. Nucl Med Commun 2002;23:727-34 (Pubitemid 34837002)
157. Zuetenhorst JM, Hoefnageli CA, Boot H, et al. Evaluation of 111In-pentetreotide, 131I-MIBG and bone scintigraphy in the detection and clinical management of bone metastases in carcinoid disease. Nucl Med Commun 2002;23:735-41 (Pubitemid 34837003)
158. Tsagarakis S, Christoforaki M, Giannopoulou H, et al. A reappraisal of the utility of somatostatin receptor scintigraphy in patients with ectopic adrenocorticotropin Cushings syndrome. J Clin Endocrinol Metab 2003;88:4754-8 (Pubitemid 37357522)
159. Reubi JC, Waser B. Concomitant expression of several peptide receptors in neuroendocrine tumours: molecular basis for in vivo multireceptor tumour targeting. Eur J Nucl Med Mol Imaging 2003;30:781-93 (Pubitemid 36612963)
160. Fanti S, Farsad M, Battista G, et al. Somatostatin receptor scintigraphy for bronchial carcinoid follow-up. Clin Nucl Med 2003;28:548-52 (Pubitemid 38281918)
161. Granberg D, Sundin A, Janson ET, et al. Octreoscan in patients with bronchial carcinoid tumours. Clin Endocrinol (Oxf) 2003;59:793-9 (Pubitemid 37491586)
162. Wartski M, Alberini JL, Leroy-Ladurie F, et al. Typical and atypical bronchopulmonary carcinoid tumors on FDG PET/CT imaging. Clin Nucl Med 2004;29:752-3 (Pubitemid 39410835)
163. Pacak K, Ilias I, Chen CC, et al. The role of [18F]fluorodeoxyglucose positron emission tomography and [111In]-diethylenetriaminepentaacetate- D-Phe-pentetreotide scintigraphy in the localization of ectopic adrenocorticotropin-secreting tumors causing Cushings syndrome. J Clin Endocrinol Metab 2004;89:2214-21 (Pubitemid 38619855)
164. Plachcinska A, Mikolajczak R, Maecke H, et al. Efficacy of 99mTc-EDDA/HYNIC-TOC scintigraphy in differential diagnosis of solitary pulmonary nodules. Cancer Biother Radiopharm 2004;19:613-20 (Pubitemid 39546301)
165. Orlefors H, Sundin A, Garske U, et al. Whole-body 11C-5-hydroxytryptophan positron emission tomography as a universal imaging technique for neuroendocrine tumors: comparison with somatostatin receptor scintigraphy and computed tomography. J Clin Endocrinol Metab 2005;90:3392-400 (Pubitemid 41014303)
166. Yellin A, Zwas ST, Rozenman J, et al. Experience with somatostatin receptor scintigraphy in the management of pulmonary carcinoid tumors. Isr Med Assoc J 2005;7:712-16 (Pubitemid 41700795)
167. Koopmans KP, de Vries EG, Kema IP, et al. Staging of carcinoid tumours with 18F-DOPA PET: a prospective, diagnostic accuracy study. Lancet Oncol 2006;7:728-34 (Pubitemid 44283659)
168. Kruger S, Buck AK, Blumstein NM, et al. Use of integrated FDG PET/CT imaging in pulmonary carcinoid tumours. J Intern Med 2006;260:545-50 (Pubitemid 44772374)
169. Hubalewska-Dydejczyk A, Fross-Baron K, Mikolajczak R, et al. 99mTc-EDDA/HYNIC-octreotate scintigraphy, an efficient method for the detection and staging of carcinoid tumours: results of 3 years experience. Eur J Nucl Med Mol Imaging 2006;33:1123-33 (Pubitemid 44488531)
170. Volante M, Brizzi MP, Faggiano A, et al. Somatostatin receptor type 2A immunohistochemistry in neuroendocrine tumors: a proposal of scoring system correlated with somatostatin receptor scintigraphy. Mod Pathol 2007;20:1172-82 (Pubitemid 47609066)
171. Chong S, Lee KS, Kim BT, et al. Integrated PET/CT of pulmonary neuroendocrine tumors: diagnostic and prognostic implications. AJR Am J Roentgenol 2007;188:1223-31 (Pubitemid 46668502)
172. Daniels CE, Lowe VJ, Aubry MC, et al. The utility of fluorodeoxyglucose positron emission tomography in the evaluation of carcinoid tumors presenting as pulmonary nodules. Chest 2007;131:255-60 (Pubitemid 46123001)
173. Song YS, Lee WW, Chung JH, et al. Correlation between FDG uptake and glucose transporter type 1 expression in neuroendocrine tumors of the lung. Lung Cancer 2008;61:54-60
174. Kayani I, Bomanji JB, Groves A, et al. Functional imaging of neuroendocrine tumors with combined PET/CT using 68Ga-DOTATATE (DOTA-DPhe1, Tyr3-octreotate) and 18F-FDG. Cancer 2008;112:2447-55
175. Korner MU, Hayes GM, Carrigan PE, et al. Wild-type and splice-variant secretin receptors in lung cancer: overexpression in carcinoid tumors and peritumoral lung tissue. Mod Pathol 2008;21:387-95 (Pubitemid 351441026)
176. Kayani I, Conry BG, Groves AM, et al. A comparison of 68Ga-DOTATATE and 18F-FDG PET/CT in pulmonary neuroendocrine tumors. J Nucl Med 2009;50:1927-32
177. Miederer M, Seidl S, Buck A, et al. Correlation of immunohistopathological expression of somatostatin receptor 2 with standardised uptake values in 68Ga-DOTATOC PET/CT. Eur J Nucl Med Mol Imaging 2009;36:48-52
178. Ambrosini V, Castellucci P, Rubello D, et al. 68Ga-DOTA-NOC: a new PET tracer for evaluating patients with bronchial carcinoid. Nucl Med Commun 2009;30:281-6
179. Kumar A, Jindal T, Dutta R, et al. Functional imaging in differentiating bronchial masses: an initial experience with a combination of 18F-FDG PET-CT scan and 68Ga DOTA-TOC PET-CT scan. Ann Nucl Med 2009;23:745-51
180. Putzer D, Gabriel M, Henninger B, et al. Bone metastases in patients with neuroendocrine tumor: 68Ga-DOTA-Tyr3-octreotide PET in comparison to CT and bone scintigraphy. J Nucl Med 2009;50:1214-21
181. Reubi JC, Waser B, Cescato R, et al. Internalized somatostatin receptor subtype 2 in neuroendocrine tumors of octreotide-treated patients. J Clin Endocrinol Metab 2010;95:2343-50
182. Binderup T, Knigge U, Loft A, et al. Functional imaging of neuroendocrine tumors: a head-to-head comparison of somatostatin receptor scintigraphy, 123I-MIBG scintigraphy, and 18F-FDG PET. J Nucl Med 2010;51:704-12
183. Srirajaskanthan R, Kayani I, Quigley AM, et al. The role of 68Ga-DOTATATE PET in patients with neuroendocrine tumors and negative or equivocal findings on 111In-DTPA-octreotide scintigraphy. J Nucl Med 2010;51:875-82
184. Korner M, Eltschinger V, Waser B, et al. Value of immunohistochemistry for somatostatin receptor subtype sst2A in cancer tissues: lessons from the comparison of anti-sst2A antibodies with somatostatin receptor autoradiography. Am J Surg Pathol 2005;29:1642-51
185. Rodrigues M, Gabriel M, Heute D, et al. Concordance between results of somatostatin receptor scintigraphy with 111In-DOTA-DPhe1-Tyr3-octreotide and chromogranin A assay in patients with neuroendocrine tumours. Eur J Nucl Med Mol Imaging 2008;35:1796-802
186. Campana D, Ambrosini V, Pezzilli R, et al. Standardized uptake values of 68Ga-DOTANOC PET: a promising prognostic tool in neuroendocrine tumors. J Nucl Med 2010;51:353-9
187. Garin E, Le Jeune F, Devillers A, et al. Predictive value of 18F-FDG PET and somatostatin receptor scintigraphy in patients with metastatic endocrine tumors. J Nucl Med 2009;50:858-64
188. Haug A, Auernhammer CJ, Wangler B, et al. Intraindividual comparison of 68Ga-DOTA-TATE and 18F-DOPA PET in patients with well-differentiated metastatic neuroendocrine tumours. Eur J Nucl Med Mol Imaging 2009;36:765-70
189. Gotthardt M, Behe MP, Grass J, et al. Added value of gastrin receptor scintigraphy in comparison to somatostatin receptor scintigraphy in patients with carcinoids and other neuroendocrine tumours. Endocr Relat Cancer 2006;13:1203-11 (Pubitemid 46212574)
190. Reubi JC, Laderach U, Waser B, et al. Vasoactive intestinal peptide/pituitary adenylate cyclase-activating peptide receptor subtypes in human tumors and their tissues of origin. Cancer Res 2000;60:3105-12 (Pubitemid 30395841)
191. Reubi JC, Schaer JC, Waser B. Cholecystokinin(CCK)-A and CCK-B/gastrin receptors in human tumors. Cancer Res 1997;57:1377-86 (Pubitemid 27152565)
192. Reubi JC, Wenger S, Schmuckli-Maurer J, et al. Bombesin receptor subtypes in human cancers: detection with the universal radioligand 125I-[D-TYR6, beta-ALA11, PHE13, NLE14] bombesin(6-14). Clin Cancer Res 2002;8:1139-46 (Pubitemid 35177367)
193. Reubi JC, Kvols LK, Waser B, et al. Detection of somatostatin receptors in surgical and percutaneous needle biopsy samples of carcinoids and islet cell carcinomas. Cancer Res 1990;50:5969-77 (Pubitemid 20331408)
194. Khan MU, Morse M, Coleman RE. Radioiodinated metaiodobenzylguanidine in the diagnosis and therapy of carcinoid tumors. Q J Nucl Med Mol Imaging 2008;52:441-54
195. Virgolini IJ, Gabriel M, von Guggenberg E, et al. Role of radiopharmaceuticals in the diagnosis and treatment of neuroendocrine tumours. Eur J Cancer 2009;45(Suppl 1):274-91
196. Antunes P, Ginji M, Zhang H, et al. Are radiogallium-labelled DOTA-conjugated somatostatin analogues superior to those labelled with other radiometals? Eur J Nucl Med Mol Imaging 2007;34:982-93 (Pubitemid 46919547)
197. Krenning E, Bakker W, Kwekkeboom D, et al. Biodistribution of a new chelated somatostatin analogue, [In-111-DOTA-DPhe1- Tyr3]- octreotide; comparison with [111In-DTPA-D-Phe1]-octreotide in humans. J Nucl Med 1997;38:103
198. Smith-Jones P, Bischof C, Leimer M, et al. MAURITIUS: a novel tumour diagnostic and therapeutic somatostatin analogue. Endocrinology 1999;140:5136-48
199. Maina T, Nock B, Nikolopoulou A, et al. [99mTc]demotate, a new 99mTc-based [Tyr3]octreotate analogue for the detection of somatostatin receptor-positive tumours: synthesis and preclinical results. Eur J Nucl Med 2002;29:742-53
200. De Jong M, Bernard B, De Bruin E, et al. Internalization of radiolabelled [DTPA0]octreotide and [DOTA0,Tyr3] octreotide: peptides for somatostatin receptor-targeted scintigraphy and radionuclide therapy. Nucl Med Commun 1998;19:283-8 (Pubitemid 28198201)
201. Wild D, Schmitt JS, Ginj M, et al. DOTA-NOC, a high-affinity ligand of somatostatin receptor subtypes 2, 3 and 5 for labeling with various radiometals. Eur J Nucl Med Mol Imaging 2003;30:1338-47 (Pubitemid 37247950)
202. Reyhan M, Aydin M, Yapar AF, et al. Atypical carcinoid tumor detected incidentally on Tc-99m sestamibi myocardial perfusion scintigraphy. Clin Nucl Med 2004;29:129-31
203. Yapar Z, Kibar M, Sukan A, et al. Coincidental visualization of an atypical bronchial carcinoid on Tc-99m-sestamibi scan in Kallmanns syndrome. Ann Nucl Med 2002;16:61-5 (Pubitemid 34302895)
204. Isidori AM, Kaltsas G, Frajese V, et al. Ocular metastases secondary to carcinoid tumors: the utility of imaging with [123I]meta-iodobenzylguanidine and [111In]DTPA pentetreotide. J Clin Endocrinol Metab 2002;87:1627-33 (Pubitemid 34615250)
205. Rodriguez JA, Meyers MO, Jacome TH, et al. Intraoperative detection of a bronchial carcinoid with a radiolabeled somatostatin analog. Chest 2002;121:985-8 (Pubitemid 34251469)
206. Grossrubatscher E, Vignati F, Dalino P, et al. Use of radioguided surgery with [111In]-pentetreotide in the management of an ACTH-secreting bronchial carcinoid causing ectopic Cushings syndrome. J Endocrinol Invest 2005;28:72-8 (Pubitemid 43162813)
207. Oberg K, Hellman P, Kwekkeboom D, et al. Neuroendocrine bronchial and thymic tumours: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2010;21(Suppl 5):v220-2
208. Travis WD, Giroux DJ, Chansky K, et al. The IASLC Lung Cancer Staging Project: proposals for the inclusion of bronchopulmonary carcinoid tumors in the forthcoming (seventh) edition of the TNM Classification for lung cancer. J Thorac Oncol 2008;3:1213-23
209. Druce MR, Lewington V, Grossman AB. Targeted radionuclide therapy for neuroendocrine tumours: principles and application. Neuroendocrinology 2010;91:1-15
210. Filosso PL, Ruffini E, Oliaro A, et al. Long-term survival of atypical bronchial carcinoids with liver metastases, treated with octreotide. Eur J Cardiothorac Surg 2002;21:913-17 (Pubitemid 34308953)
211. Hearn PR, Reynolds CL, Johansen K, et al. Lung carcinoid with Cushings syndrome: control of serum ACTH and cortisol levels using SMS 201-995 (sandostatin). Clin Endocrinol (Oxf ) 1988;28:181-5 (Pubitemid 18055755)
212. Lefebvre H, Jegou S, Leroux P, et al. Characterization of the somatostatin receptor subtype in a bronchial carcinoid tumor responsible for Cushings syndrome. J Clin Endocrinol Metab 1995;80:1423-8
213. Melmed S, Ziel FH, Braunstein GD, et al. Medical management of acromegaly due to ectopic production of growthhormone releasing hormone by a carcinoid tumor. J Clin Endocrinol Metab 1988;67:395-9
214. Moller DE, Moses AC, Jones K, et al. Octreotide suppresses both growth hormone (GH) and GH-releasing hormone (GHRH) in acromegaly due toectopic GHRH secretion. J Clin Endocrinol Metab 1989;68:499-504 (Pubitemid 19052899)
215. Boizel R, Halimi S, Labat F, et al. Acromegaly due to a growth hormone-releasing hormone-secreting bronchial carcinoid tumor: further information on the abnormal responsiveness of the somatotroph cells and their recovery after successful treatment. J Clin Endocrinol Metab 1987;64:304-8 (Pubitemid 17001063)
216. Fainstein Day P, Frohman L, Garcia Rivello H, et al. Ectopic growth hormone-releasing hormone secretion by a metastatic bronchial carcinoid tumor: a case with a non hypophysial intracranial tumor that shrank during long acting octreotide treatment. Pituitary 2007;10:311-19 (Pubitemid 350055045)
217. Reith P, Monnot EA, Bathija PJ. Prolonged suppression of a corticotropin-producing bronchial carcinoid by oral bromocriptine. Arch Intern Med 1987;147:989-91 (Pubitemid 17082497)
218. Francia G, Davi MV, Montresor E, et al. Long-term quiescence of ectopic Cushings syndrome caused by pulmonary neuroendocrine tumor (typical carcinoid) and tumorlets: spontaneous remission or therapeutic effect of bromocriptine? J Endocrinol Invest 2006;29:358-62 (Pubitemid 43905328)
219. Granberg D, Eriksson B, Wilander E, et al. Experience in treatment of metastatic pulmonary carcinoid tumors. Ann Oncol 2001;12:1383-91 (Pubitemid 33100242)
220. Moertel CG, Hanley JA. Combination chemotherapy trials in metastatic carcinoid tumor and the malignant carcinoid syndrome. Cancer Clin Trials 1979;2:327-34 (Pubitemid 10021790)
221. Guigay J, Ruffie P, Leboulleux S, et al. Response of atypical pulmonary carcinoid tumors to chemotherapy. A retrospective study of 37 patients. J Thorac Oncol 2007;2(Suppl 4):S599
222. Bajetta E, Ferrari L, Procopio G, et al. Efficacy of a chemotherapy combination for the treatment of metastatic neuroendocrine tumours. Ann Oncol 2002;13:614-21 (Pubitemid 34461146)
223. Bajetta E, Catena L, Procopio G, et al. Are capecitabine and oxaliplatin (XELOX) suitable treatments for progressing low-grade and high-grade neuroendocrine tumours? Cancer Chemother Pharmacol 2007;59:637-42 (Pubitemid 46295128)
224. Ekeblad S, Sundin A, Janson ET, et al. Temozolomide as monotherapy is effective in treatment of advanced malignant neuroendocrine tumors. Clin Cancer Res 2007;13:2986-91 (Pubitemid 46849574)
225. Waldherr C, Pless M, Maecke HR, et al. The clinical value of [90Y-DOTA]-DPhe1- Tyr3-octreotide (90Y-DOTATOC) in the treatment of neuroendocrine tumours: a clinical phase II study. Ann Oncol 2001;12:941-5 (Pubitemid 32725766)
226. Waldherr C, Pless M, Maecke HR, et al. Tumor response and clinical benefit in neuroendocrine tumors after 7.4 GBq 90Y-DOTATOC. J Nucl Med 2002;43:610-16 (Pubitemid 34507110)
227. Bodei L, Cremonesi M, Zoboli S, et al. Receptor-mediated radionuclide therapy with 90Y-DOTATOC in association with amino acid infusion: a phase I study. Eur J Nucl Med Mol Imaging 2003;30:207-16 (Pubitemid 36686839)
228. Bodei L, Cremonesi M, Grana C, et al. Receptor radionuclide therapy with 90Y-[DOTA]0-Tyr3-octreotide (90Y-DOTATOC) in neuroendocrine tumours. Eur J Nucl Med Mol Imaging 2004;31:1038-46 (Pubitemid 38915663)
229. van Essen M, Krenning EP, Bakker WH, et al. Peptide receptor radionuclide therapy with 177Lu-octreotate in patients with foregut carcinoid tumours of bronchial, gastric and thymic origin. Eur J Nucl Med Mol Imaging 2007;34:1219-27 (Pubitemid 47290659)
230. van Essen M, Krenning EP, Kam BL, et al. Salvage therapy with 177Lu-octreotate in patients with bronchial and gastroenteropancreatic neuroendocrine tumors. J Nucl Med 2010;51:383-90
231. Seregni E, Maccauro M, Coliva A, et al. Treatment with tandem [90Y]DOTATATE an [177Lu] DOTA-TATE of neuroendocrine tumors refractory to conventional therapy: preliminary results. Q J Nucl Med Mol Imaging 2010;54:84-91
232. +/calmodulin antagonist B859-35 and the Ca(2+)-channel blocker verapamil on human lung cancer cell lines. Carcinogenesis 1991;12:2301-3
233. Marshall ME, Kervin K, Benefield C, et al. Growth-inhibitory effects of coumarin (1,2-benzopyrone) and 7-hydroxycoumarin on human malignant cell lines in vitro. J Cancer Res Clin Oncol 1994;120:S3-10 (Pubitemid 24142544)
234. Gilbert JA, Frederick LM, Ames MM. The aromatic-L-amino acid decarboxylase inhibitor carbidopa is selectively cytotoxic to human pulmonary carcinoid and small cell lung carcinoma cells. Clin Cancer Res 2000;6:4365-72
235. Goke R, Goke A, Goke B, et al. Pioglitazone inhibits growth of carcinoid cells and promotes TRAIL-induced apoptosis by induction of p21waf1/cip1. Digestion 2001;64:75-80 (Pubitemid 34701873)
236. Gilbert JA, Frederick LM, Pobst LJ, et al. Hydrogen peroxide degradation and selective carbidopa-induced cytotoxicity against human tumor lines. Biochem Pharmacol 2005;69:1159-66 (Pubitemid 40417487)
237. Van Gompel JJ, Kunnimalaiyaan M, Holen K, et al. ZM336372, a Raf-1 activator, suppresses growth and neuroendocrine hormone levels in carcinoid tumor cells. Mol Cancer Ther 2005;4:910-17 (Pubitemid 40909073)
238. Nakamura H, Takamori S, Fujii T, et al. Cooperative cell-growth inhibition by combination treatment with ZD1839 (Iressa) and trastuzumab (Herceptin) in non-small-cell lung cancer. Cancer Lett 2005;230:33-46 (Pubitemid 41506958)
239. Mayburd AL, Martlinez A, Sackett D, et al. Ingenuity network-assisted transcription profiling: identification of a new pharmacologic mechanism for MK886. Clin Cancer Res 2006;12:1820-7
240. Larsson DE, Lovborg H, Rickardson L, et al. Identification and evaluation of potential anti-cancer drugs on humanneuroendocrine tumor cell lines. Anticancer Res 2006;26:4125-9 (Pubitemid 46031481)
241. Yao JC, Zhang JX, Rashid A, et al. Clinical and in vitro studies of imatinib in advanced carcinoid tumors. Clin Cancer Res 2007;13:234-40 (Pubitemid 46121874)
242. Ono K, Suzuki T, Miki Y, et al. Somatostatin receptor subtypes in human non-functioning neuroendocrine tumors and effects of somatostatin analogue SOM230 on cell proliferation in cell line NCI-H727. Anticancer Res 2007;27:2231-9 (Pubitemid 47228058)
243. Greenblatt DY, Cayo M, Ning L, et al. Suberoyl bishydroxamic acid inhibits cellular proliferation by inducing cell cycle arrest in carcinoid cancer cells. J Gastrointest Surg 2007;11:1515-20
244. Greenblatt DY, Vaccaro AM, Jaskula-Sztul R, et al. Valproic acid activates notch-1 signaling and regulates the neuroendocrine phenotype in carcinoid cancer cells. Oncologist 2007;12:942-51 (Pubitemid 47359136)
245. Kunnimalaiyaan M, Ndiaye M, Chen H. Neuroendocrine tumor cell growth inhibition by ZM336372 through alterations in multiple signaling pathways. Surgery 2007;142:959-64 (Pubitemid 350184109)
246. Mijatovic T, Roland I, Van Quaquebeke E, et al. The alpha1 subunit of the sodium pump could represent a novel target to combat non-small cell lung cancers. J Pathol 2007;212:170-9 (Pubitemid 46852095)
247. Sacewicz M, Lawnicka H, Siejka A, et al. Inhibition of proliferation, VEGF secretion of human neuroendocrine tumor cell line NCI-H727 by an antagonist of growth hormone-releasing hormone (GH-RH) in vitro. Cancer Lett 2008;268:120-8
248. Kidd M, Schally AV, Pfragner R, et al. Inhibition of proliferation of small intestinal and bronchopulmonary neuroendocrine cell lines by using peptide analogs targeting receptors. Cancer 2008;112:1404-14 (Pubitemid 351429756)
249. Kidd M, Drozdov I, Joseph R, et al. Differential cytotoxicity of novel somatostatin and dopamine chimeric compounds on bronchopulmonary and small intestinal neuroendocrine tumor cell lines. Cancer 2008;113:690-700
250. Moreno A, Akcakanat A, Munsell MF, et al. Antitumor activity of rapamycin and octreotide as single agents or in combination in neuroendocrine tumors. Endocr Relat Cancer 2008;15:257-66 (Pubitemid 351449744)
251. Larsson DE, Hassan S, Larsson R, et al. Combination analyses of anti-cancer drugs on human neuroendocrine tumor cell lines. Cancer Chemother Pharmacol 2009;65:5-12
252. Adler JT, Hottinger DG, Kunnimalaiyaan M, et al. Combination therapy with histone deacetylase inhibitors and lithium chloride: a novel treatment for carcinoid tumors. Ann Surg Oncol 2009;16:481-6
253. Drozdov I, Kidd M, Gustafsson BI, et al. Autoregulatory effects of serotonin on proliferation and signaling pathways in lung and small intestine neuroendocrine tumor cell lines. Cancer 2009;115:4934-45
254. Pinchot SN, Adler JT, Luo Y, et al. Tautomycin suppresses growth and neuroendocrine hormone markers in carcinoid cells through activation of the Raf-1 pathway. Am J Surg 2009;197:313-19
255. Alexander VM, Roy M, Steffens KA, et al. Azacytidine induces cell cycle arrest and suppression of neuroendocrine markers in carcinoids. Int J Clin Exp Med 2010;3:95-102
256. Chen JY, Cook MR, Pinchot SN, et al. MG-132 inhibits carcinoid growth and alters the neuroendocrine phenotype. J Surg Res 2010;158:15-19
257. Greenblatt DY, Ndiaye M, Chen H, et al. Lithium inhibits carcinoid cell growth in vitro. Am J Transl Res 2010;2:248-53
258. Larsson DE, Wickstrom M, Hassan S, et al. The cytotoxic agents NSC-95397, brefeldin A, bortezomib and sanguinarine induce apoptosis in neuroendocrine tumors in vitro. Anticancer Res 2010;30:149-56
259. Zatelli MC, Minoia M, Martini C, et al. Everolimus as a new potential antiproliferative agent in aggressive human bronchial carcinoids. Endocr Relat Cancer 2010;17:719-29
260. Cakir M, Grossman AB. Targeting MAPK (Ras/ERK) and PI3K/Akt pathways in pituitary tumorigenesis. Expert Opin Ther Targets 2009;13:1121-34
261. Zhang J, Jin W, Wang X, et al. A novel octreotide modified lipid vesicle improved the anticancer efficacy of doxorubicin in somatostatin receptor 2 positive tumor models. Mol Pharm 2010;7:1159-68
262. Lim E, Goldstraw P, Nicholson AG, et al. Proceedings of the IASLC International Workshop on Advances in Pulmonary Neuroendocrine Tumors 2007. J Thorac Oncol 2008;3:1194-201