Expression and therapeutic relevance of heat-shock protein 90 in pancreatic endocrine tumors

Endocrine-Related Cancer

Volumn 19, Issue 3, 2012, Pages 217-232

  Mayer, Philipp ^a   Harjung, Andreas ^a   Breinig, Marco ^a   Fischer, Lars ^a   Ehemann, Volker ^a   Malz, Mona ^a   Scherübl, Hans ^b   Britsch, Sarah ^a   Werner, Jens ^a   Kern, Michael A ^a   Bläker, Hendrik ^a   Schirmacher, Peter ^a   Bergmann, Frank ^a  

^a UNIVERSITY OF HEIDELBERG   (Germany)

^b VIVANTES KLINIKUM AM URBAN   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

ALVESPIMYCIN; DOXORUBICIN; FLUOROURACIL; GLUCOSE RELATED PROTEIN 94; HEAT SHOCK PROTEIN 90; HEAT SHOCK PROTEIN 90ALPHA; HEAT SHOCK PROTEIN 90BETA; ISOPROTEIN; TANESPIMYCIN; TUMOR NECROSIS FACTOR RECEPTOR ASSOCIATED FACTOR 1; UNCLASSIFIED DRUG;

ADULT; AGED; ANIMAL TISSUE; APOPTOSIS; ARTICLE; CARCINOID; CELL CYCLE ARREST; CELL VIABILITY; CONCENTRATION RESPONSE; CONTROLLED STUDY; FEMALE; HISTOPATHOLOGY; HUMAN; HUMAN TISSUE; IMMUNOHISTOCHEMISTRY; INSULINOMA; MAJOR CLINICAL STUDY; MALE; MOUSE; NONHUMAN; PANCREAS ISLET CELL TUMOR; PROTEIN EXPRESSION; QUANTITATIVE ANALYSIS; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION;

ADOLESCENT; ADULT; AGED; AGED, 80 AND OVER; ANIMALS; ANTIBIOTICS, ANTINEOPLASTIC; ANTIMETABOLITES, ANTINEOPLASTIC; APOPTOSIS; BENZOQUINONES; CELL LINE, TUMOR; CELL SURVIVAL; DOXORUBICIN; FEMALE; FLUOROURACIL; GENE EXPRESSION REGULATION, NEOPLASTIC; HSP90 HEAT-SHOCK PROTEINS; HUMANS; LACTAMS, MACROCYCLIC; MALE; MICE; MIDDLE AGED; MULTIPLE ENDOCRINE NEOPLASIA TYPE 1; PANCREATIC NEOPLASMS; RNA, MESSENGER; YOUNG ADULT;

EID: 84862638382     PISSN: 13510088     EISSN: 14796821     Source Type: Journal    
DOI: 10.1530/ERC-11-0227     Document Type: Article

References (75)

1. Abramson JS, Chen W, Juszczynski P, Takahashi H, Neuberg D, Kutok JL, Takeyama K & Shipp MA 2009 The heat shock protein 90 inhibitor IPI-504 induces apoptosis of AKT-dependent diffuse large B-cell lymphomas. British Journal of Haematology 144 358-366. (doi:10.1111/j.1365-2141.2008.07484.x)
2. Altieri DC 2010 Mitochondrial HSP90 chaperones as novel molecular targets in prostate cancer. Future Oncology 6 487-489. (doi:10.2217/fon.10.26)
3. Baselga J 2010 Treatment of HER2-overexpressing breast cancer. Annals of Oncology 21 (Suppl 7) vii36-vii40. (doi:10.1093/annonc/mdq421)
4. Bergmann F, Breinig M, Hopfner M, Rieker RJ, Fischer L, Kohler C, Esposito I, Kleeff J, Herpel E, Ehemann V et al. 2009 Expression pattern and functional relevance of epidermal growth factor receptor and cyclooxygenase-2: novel chemotherapeutic targets in pancreatic endocrine tumors? American Journal of Gastroenterology 104 171-181. (doi:10.1038/ajg.2008.33)
5. Bertram J, Palfner K, Hiddemann W & Kneba M 1996 Increase of P-glycoprotein-mediated drug resistance by hsp 90 beta. Anticancer Drugs 7 838-845. (doi:10.1097/ 00001813-199611000-00004)
6. Biamonte MA, Van de Water R, Arndt JW, Scannevin RH, Perret D & Lee WC 2010 Heat shock protein 90: inhibitors in clinical trials. Journal of Medicinal Chemistry 53 3-17. (doi:10.1021/jm9004708)
7. Breinig M, Caldas-Lopes E, Goeppert B, Malz M, Rieker R, Bergmann F, Schirmacher P, Mayer M, Chiosis G &Kern MA 2009 Targeting heat shock protein 90 with non-quinone inhibitors: a novel chemotherapeutic approach in human hepatocellular carcinoma. Hepatology 50 102-112. (doi:10.1002/hep.22912)
8. Burkitt M, Magee C, O'Connor D, Campbell F, Cornford P &Greenhalf W 2007 Potentiation of chemotherapeutics by the HSP90 antagonist geldanamycin requires a steady serum condition. Molecular Carcinogenesis 46 466-475. (doi:10.1002/mc.20296)
9. Caldas-Lopes E, Cerchietti L, Ahn JH, Clement CC, Robles AI, Rodina A, Moulick K, Taldone T, Gozman A, Guo Y et al. 2009 HSP90 inhibitor PU-H71, a multimodal inhibitor of malignancy, induces complete responses in triple-negative breast cancer models. PNAS 106 8368-8373. (doi:10.1073/pnas. 0903392106)
10. Carracedo A, Ma L, Teruya-Feldstein J, Rojo F, Salmena L, Alimonti A, Egia A, Sasaki AT, Thomas G, Kozma SC et al. 2008 Inhibition of mTORC1 leads to MAPK pathway activation through a PI3K-dependent feedback loop in human cancer. Journal of Clinical Investigation 118 3065-3074.
11. Chen B, Piel WH, Gui L, Bruford E & Monteiro A 2005 The HSP90 family of genes in the human genome: insights into their divergence and evolution. Genomics 86 627-637. (doi:10.1016/j.ygeno.2005.08.012)
12. Costantino E, Maddalena F, Calise S, Piscazzi A, Tirino V, Fersini A, Ambrosi A, Neri V, Esposito F & Landriscina M 2009 TRAP1, a novel mitochondrial chaperone responsible for multi-drug resistance and protection from apoptotis in human colorectal carcinoma cells. Cancer Letters 279 39-46. (doi:10.1016/j.canlet.2009.01.018)
13. Csermely P, Schnaider T, Soti C, Prohaszka Z & Nardai G 1998 The 90-kDa molecular chaperone family: structure, function, and clinical applications. A comprehensive review. Pharmacology & Therapeutics 79 129-168. (doi:10.1016/S0163-7258(98)00013-8)
14. Ehemann V, Hashemi B, Lange A & Otto HF 1999 Flow cytometric DNA analysis and chromosomal aberrations in malignant glioblastomas. Cancer Letters 138 101-106. (doi:10.1016/S0304-3835(98)00383-8)
15. Ehemann V, Sykora J, Vera-Delgado J, Lange A & Otto HF 2003 Flow cytometric detection of spontaneous apoptosis in human breast cancer using the TUNEL-technique. Cancer Letters 194 125-131. (doi:10.1016/S0304-3835 (03)00054-5)
16. Elmore LW, Forsythe R, Forsythe H, Bright AT, Nasim S, Endo K & Holt SE 2008 Overexpression of telomerase-associated chaperone proteins in prostatic intraepithelial neoplasia and carcinomas. Oncology Reports 20 613-617. (doi:10:3892/or-00000049)
17. Eriksson B, Annibale B, Bajetta E, Mitry E, Pavel M, Platania M, Salazar R & Plockinger U 2009 ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: chemotherapy in patients with neuroendocrine tumors. Neuroendocrinology 90 214-219. (doi:10.1159/000225950)
18. Fatrai S, Elghazi L, Balcazar N, Cras-Meneur C, Krits I, Kiyokawa H & Bernal-Mizrachi E 2006 Akt induces beta-cell proliferation by regulating cyclin D1, cyclin D2, and p21 levels and cyclin-dependent kinase-4 activity. Diabetes 55 318-325. (doi:10.2337/diabetes.55.02.06. db05-0757)
19. Ge J, Normant E, Porter JR, Ali JA, Dembski MS, Gao Y, Georges AT, Grenier L, Pak RH, Patterson J et al. 2006 Design, synthesis, and biological evaluation of hydroquinone derivatives of 17-amino-17-demethoxygeldanamycin as potent, water-soluble inhibitors of HSP90. Journal of Medicinal Chemistry 49 4606-4615. (doi:10. 1021/jm0603116)
20. Gossett DR, Bradley MS, Jin X & Lin J 2005 17-Allyamino- 17-demethoxygeldanamycin and 17-NN-dimethyl ethylene diamine-geldanamycin have cytotoxic activity against multiple gynecologic cancer cell types. Gynecologic Oncology 96 381-388. (doi:10.1016/j.ygyno.2004.10.009)
21. Grant S 2008 Cotargeting survival signaling pathways in cancer. Journal of Clinical Investigation 118 3003-3006. (doi:10.1172/JCI36898E1)
22. Grbovic OM, Basso AD, Sawai A, Ye Q, Friedlander P, Solit D & Rosen N 2006 V600E B-Raf requires the HSP90 chaperone for stability and is degraded in response to HSP90 inhibitors. PNAS 103 57-62. (doi:10.1073/pnas. 0609973103)
23. Guo SS, Wu X, Shimoide AT, Wong J, Moatamed F &Sawicki MP 2003 Frequent overexpression of cyclin D1 in sporadic pancreatic endocrine tumours. Journal of Endocrinology 179 73-79. (doi:10.1677/joe.0.1790073)
24. Hansel DE, Rahman A, House M, Ashfaq R, Berg K, Yeo CJ & Maitra A 2004 Met proto-oncogene and insulin-like growth factor binding protein 3 overexpression correlates with metastatic ability in well-differentiated pancreatic endocrine neoplasms. Clinical Cancer Research 10 6152-6158. (doi:10.1158/1078-0432.CCR-04-0285)
25. Hanson BE & Vesole DH 2009 Retaspimycin hydrochloride (IPI-504): a novel heat shock protein inhibitor as an anticancer agent. Expert Opinion on Investigational Drugs 18 1375-1383. (doi:10.1517/13543780903158934)
26. Hay N 2005 The Akt-mTOR tango and its relevance to cancer. Cancer Cell 8 179-183. (doi:10.1016/j.ccr.2005. 08.008)
27. Heitz PU, Komminoth P, Perren A, Klimstra DS, Dayal Y, Bordi C, Lechago J, Centeno BA & Klöppel G 2004 Pancreatic endocrine tumors: introduction. In Tumours of Endocrine Organs: Pathology and Genetics. World Health Organisation Classification of Tumors, Eds RA DeLellis, RV Lloyd, PU Heitz & C Eng. Lyon: IARC Press.
28. Hennessy BT, Smith DL, Ram PT, Lu Y & Mills GB 2005 Exploiting the PI3K/AKT pathway for cancer drug discovery. Nature Reviews. Drug Discovery 4 988-1004. (doi:10.1038/nrd1902)
29. Hollingshead M, Alley M, Burger AM, Borgel S, Pacula-Cox C, Fiebig HH & Sausville EA 2005 In vivo antitumor efficacy of 17-DMAG (17-dimethylaminoethylamino- 17-demethoxygeldanamycin hydrochloride), a watersoluble geldanamycin derivative. Cancer Chemotherapy and Pharmacology 56 115-125. (doi:10.1007/s00280- 004-0939-2)
30. Kaiser M, Lamottke B, Mieth M, Jensen MR, Quadt C, Garcia-Echeverria C, Atadja P, Heider U, von Metzler I, Turkmen S et al. 2010 Synergistic action of the novel HSP90 inhibitor NVP-AUY922 with histone deacetylase inhibitors, melphalan, or doxorubicin in multiple myeloma. European Journal of Haematology 84 337-344. (doi:10.1111/j.1600-0609.2009.01403.x)
31. Kamal A, Thao L, Sensintaffar J, Zhang L, Boehm MF, Fritz LC & Burrows FJ 2003 A high-affinity conformation of HSP90 confers tumour selectivity on HSP90 inhibitors. Nature 425 407-410. (doi:10.1038/nature01913)
32. Kang BH, Plescia J, Dohi T, Rosa J, Doxsey SJ & Altieri DC 2007 Regulation of tumor cell mitochondrial homeostasis by an organelle-specific HSP90 chaperone network. Cell 131 257-270. (doi:10.1016/j.cell.2007.08.028)
33. Kang GH, Lee EJ, Jang KT, Kim KM, Park CK, Lee CS, Kang DY, Lee SH, Sohn TS & Kim S 2010 Expression of HSP90 in gastrointestinal stromal tumours and mesenchymal tumours. Histopathology 56 694-701. (doi:10.1111/ j.1365-2559.2010.03550.x)
34. Karapanagiotou EM, Syrigos K & Saif MW 2009 Heat shock protein inhibitors and vaccines as new agents in cancer treatment. Expert Opinion on Investigational Drugs 18 161-174. (doi:10.1517/13543780802715792)
35. Karkoulis PK, Stravopodis DJ, Margaritis LH & Voutsinas GE 2010 17-Allylamino-17-demethoxygeldanamycin induces downregulation of critical HSP90 protein clients and results in cell cycle arrest and apoptosis of human urinary bladder cancer cells. BMC Cancer 10 481. (doi:10.1186/ 1471-2407-10-481)
36. Kazanjian KK, Reber HA & Hines OJ 2006 Resection of pancreatic neuroendocrine tumors: results of 70 cases. Archives of Surgery 141 765-769 (discussion 769-770). (doi:10.1001/archsurg.141.8.765)
37. Kirshbom PM, Kherani AR, Onaitis MW, Hata A, Kehoe TE, Feldman C, Feldman JM & Tyler DS 1999 Foregut carcinoids: a clinical and biochemical analysis. Surgery 126 1105-1110. (doi:10.1067/msy.2099.101430)
38. Kummar S, Gutierrez ME, Gardner ER, Chen X, Figg WD, Zajac-Kaye M, Chen M, Steinberg SM, Muir CA, Yancey MA et al. 2010 Phase I trial of 17-dimethylaminoethylamino- 17-demethoxygeldanamycin (17-DMAG), a heat shock protein inhibitor, administered twice weekly in patients with advanced malignancies. European Journal of Cancer 46 340-347. (doi:10.1016/j.ejca.2009. 10.026)
39. Lancet JE, Gojo I, Burton M, Quinn M, Tighe SM, Kersey K, Zhong Z, Albitar MX, Bhalla K, Hannah AL et al. 2010 Phase I study of the heat shock protein 90 inhibitor alvespimycin (KOS-1022, 17-DMAG) administered intravenously twice weekly to patients with acute myeloid leukemia. Leukemia 24 699-705. (doi:10.1038/leu.2009.292)
40. Lee W, Patel JH & Lockhart AC 2009 Novel targets in esophageal and gastric cancer: beyond antiangiogenesis. Expert Opinion on Investigational Drugs 18 1351-1364. (doi:10.1517/13543780903179286)
41. Mebratu Y & Tesfaigzi Y 2009 How ERK1/2 activation controls cell proliferation and cell death: is subcellular localization the answer? Cell Cycle 8 1168-1175. (doi:10. 4161/cc.8.8.8147)
42. Milicevic Z, Bogojevic D, Mihailovic M, Petrovic M &Krivokapic Z 2008 Molecular characterization of hsp90 isoforms in colorectal cancer cells and its association with tumour progression. International Journal of Oncology 32 1169-1178.
43. Missiaglia E, Dalai I, Barbi S, Beghelli S, Falconi M, della Peruta M, Piemonti L, Capurso G, Di Florio A, delle Fave G et al. 2010 Pancreatic endocrine tumors: expression profiling evidences a role for AKT-mTOR pathway. Journal of Clinical Oncology 28 245-255. (doi:10.1200/ JCO.2008.21.5988)
44. Modi S, Stopeck AT, Gordon MS, Mendelson D, Solit DB, Bagatell R, Ma W, Wheler J, Rosen N, Norton L et al. 2007 Combination of trastuzumab and tanespimycin (17-AAG, KOS-953) is safe and active in trastuzumabrefractory HER-2 overexpressing breast cancer: a phase I dose-escalation study. Journal of Clinical Oncology 25 5410-5417. (doi:10.1200/JCO.2007.11.7960)
45. Mohseni M & Park BH 2010 PIK3CA and KRAS mutations predict for response to everolimus therapy: now that's RAD001. Journal of Clinical Investigation 120 2655-2658. (doi:10.1172/JCI44026)
46. Ni M & Lee AS 2007 ER chaperones in mammalian development and human diseases. FEBS Letters 581 3641-3651. (doi:10.1016/j.febslet.2007.04.045)
47. Normant E, Paez G, West KA, Lim AR, Slocum KL, Tunkey C, McDougall J, Wylie AA, Robison K, Caliri K et al. 2011 The HSP90 inhibitor IPI-504 rapidly lowers EML4-ALK levels and induces tumor regression in ALK-driven NSCLC models. Oncogene 30 2581-2586. (doi:10.1038/onc.2010.625)
48. Ogata M, Naito Z, Tanaka S, Moriyama Y & Asano G 2000 Overexpression and localization of heat shock proteins mRNA in pancreatic carcinoma. Journal of Nippon Medical School 67 177-185. (doi:10.1272/jnms.67.177)
49. Pacey S, Gore M, Chao D, Banerji U, Larkin J, Sarker S, Owen K, Asad Y, Raynaud F, Walton M et al. 2010 A phase II trial of 17-allylamino, 17-demethoxygeldanamycin (17-AAG, tanespimycin) in patients with metastatic melanoma. Investigational New Drugs 30 341-349. (doi:10.1007/510637-010-9493-4)
50. Pan Z, Erkan M, Streit S, Friess H & Kleeff J 2009 Silencing of GRP94 expression promotes apoptosis in pancreatic cancer cells. International Journal of Oncology 35 823-828. (doi:10.3892/ijo-00000395)
51. Pearl LH, Prodromou C & Workman P 2008 The HSP90 molecular chaperone: an open and shut case for treatment. Biochemical Journal 410 439-453. (doi:10.1042/ BJ20071640)
52. Peng B, Xu L, Cao F, Wei T, Yang C, Uzan G & Zhang D 2010 HSP90 inhibitor, celastrol, arrests human monocytic leukemia cell U937 at G0/G1 in thiol-containing agents reversible way. Molecular Cancer 9 79. (doi:10.1186/ 1476-4598-9-79)
53. Pick E, Kluger Y, Giltnane JM, Moeder C, Camp RL, Rimm DL & Kluger HM 2007 High HSP90 expression is associated with decreased survival in breast cancer. Cancer Research 67 2932-2937. (doi:10.1158/0008-5472.CAN-06-4511)
54. Plockinger U, Rindi G, Arnold R, Eriksson B, Krenning EP, de Herder WW, Goede A, Caplin M, Oberg K, Reubi JC et al. 2004 Guidelines for the diagnosis and treatment of neuroendocrine gastrointestinal tumours. A consensus statement on behalf of the European Neuroendocrine Tumour Society (ENETS). Neuroendocrinology 80 394-424. (doi:10.1159/000085237)
55. Porter JR, Fritz CC & Depew KM 2010 Discovery and development of HSP90 inhibitors: a promising pathway for cancer therapy. Current Opinion in Chemical Biology 14 412-420. (doi:10.1016/j.cbpa.2010.03.019)
56. Rexen P & Emborg C 1992 Investigation of different modifications to the tetrazolium based colorimetric viability assay. Biotechnology Techniques 6 255-260. (doi:10.1007/BF02439354)
57. Richardson PG, Badros AZ, Jagannath S, Tarantolo S, Wolf JL, Albitar M, Berman D, Messina M & Anderson KC 2010 Tanespimycin with bortezomib: activity in relapsed/ refractory patients with multiple myeloma. British Journal of Haematology 150 428-437. (doi:10.1111/j. 1365-2141.2010.08264.x)
58. Riely GJ, Stoller R, Egorin M, Solit D, Dunbar J, Savage A, Walker J, Grayzel D, Ross R & Weiss GJ 2009 A phase Ib trial of IPI-504 (retaspimycin hydrochloride), a novel HSP90 inhibitor, in combination with docetaxel. Journal of Clinical Oncology 27 S3547. (doi:10.1200/ JCO.2008.17.4656)
59. Shimamura T & Shapiro GI 2008 Heat shock protein 90 inhibition in lung cancer. Journal of Thoracic Oncology 3 S152-S159. (doi:10.1097/JTO. 0b013e318174ea3a)
60. Sippel RS, Carpenter JE, Kunnimalaiyaan M, Lagerholm S &Chen H 2003 Raf-1 activation suppresses neuroendocrine marker and hormone levels in human gastrointestinal carcinoid cells. American Journal of Physiology. Gastrointestinal and Liver Physiology 285 G245-G254. (doi:10.1152/ajpgi.00420. 2002)
61. Solit DB, Osman I, Polsky D, Panageas KS, Daud A, Goydos JS, Teitcher J, Wolchok JD, Germino FJ, Krown SE et al. 2008 Phase II trial of 17-allylamino-17-demethoxygeldanamycin in patients with metastatic melanoma. Clinical Cancer Research 14 8302-8307. (doi:10.1158/1078-0432.CCR-08-1002)
62. Song D, Chaerkady R, Tan AC, Garcia-Garcia E, Nalli A, Suarez-Gauthier A, Lopez-Rios F, Zhang XF, Solomon A, Tong J et al. 2008 Antitumor activity and molecular effects of the novel heat shock protein 90 inhibitor, IPI-504, in pancreatic cancer. Molecular Cancer Therapeutics 7 3275-3284. (doi:10.1158/1535-7163. MCT-08-0508)
63. Sreedhar AS, Kalmar E, Csermely P & Shen YF 2004 HSP90 isoforms: functions, expression and clinical importance. FEBS Letters 562 11-15. (doi:10.1016/S0014-5793(04) 00229-7)
64. Suzuki Y, Kondo Y, Hara S, Kimata R & Nishimura T 2010 Effect of the hsp90 inhibitor geldanamycin on androgen response of prostate cancer under hypoxic conditions. International Journal of Urology 17 281-285. (doi:10. 1111/j.1442-2042.2010.02450.x)
65. Tannapfel A, Vomschloss S, Karhoff D, Markwarth A, Hengge UR, Wittekind C, Arnold R & Horsch D 2005 BRAF gene mutations are rare events in gastroenteropancreatic neuroendocrine tumors. American Journal of Clinical Pathology 123 256-260. (doi:10. 1309/YQBR9C05RU4DD3RN)
66. Trepel J, Mollapour M, Giaccone G & Neckers L 2010 Targeting the dynamic HSP90 complex in cancer. Nature Reviews. Cancer 10 537-549. (doi:10.1038/nrc2887)
67. Usmani SZ, Bona R & Li Z 2009 17 AAG for HSP90 inhibition in cancer - from bench to bedside. Current Molecular Medicine 9 654-664. (doi:10.2174/ 156652409788488757)
68. von Wichert G, Jehle PM, Hoeflich A, Koschnick S, Dralle H, Wolf E, Wiedenmann B, Boehm BO, Adler G &Seufferlein T 2000 Insulin-like growth factor-I is an autocrine regulator of chromogranin A secretion and growth in human neuroendocrine tumor cells. Cancer Research 60 4573-4581. (Pubitemid 32103642)
69. Workman P 2004 Combinatorial attack on multistep oncogenesis by inhibiting the HSP90 molecular chaperone. Cancer Letters 206 149-157. (doi:10.1016/j.canlet. 2003.08.032)
70. Workman P, Burrows F, Neckers L & Rosen N 2007 Drugging the cancer chaperone HSP90: combinatorial therapeutic exploitation of oncogene addiction and tumor stress. Annals of the New York Academy of Sciences 1113 202-216. (doi:10.1196/annals.1391.012)
71. Wu X, Wanders A, Wardega P, Tinge B, Gedda L, Bergstrom S, Sooman L, Gullbo J, Bergqvist M, Hesselius P et al. 2009 HSP90 is expressed and represents a therapeutic target in human oesophageal cancer using the inhibitor 17-allylamino- 17-demethoxygeldanamycin. British Journal of Cancer 100 334-343. (doi:10.1038/sj.bjc.6604855)
72. Yu WJ, Rao Q, Wang M, Tian Z, Liu XR, Lin D & Wang JX 2005 The heat shock protein 90 inhibitor induces apoptosis and differentiation of Kasumi-1 and its mechanisms. Zhonghua Xue Ye Xue Za Zhi 26 728-731.
73. Zhang WL, Gao XQ, Han JX, Wang GQ & Yue LT 2009 Expressions of heat shock protein (HSP) family HSP 60, 70 and 90alpha in colorectal cancer tissues and their correlations to pathohistological characteristics. Ai Zheng 28 612-618.
74. Zikusoka MN, Kidd M, Eick G, Latich I & Modlin IM 2005 The molecular genetics of gastroenteropancreatic neuroendocrine tumors. Cancer 104 2292-2309. (doi:10.1002/cncr.21451)
75. Zitzmann K, De Toni EN, Brand S, Goke B, Meinecke J, Spottl G, Meyer HH & Auernhammer CJ 2007 The novel mTOR inhibitor RAD001 (everolimus) induces antiproliferative effects in human pancreatic neuroendocrine tumor cells. Neuroendocrinology 85 54-60. (doi:10.1159/000100057)