Hotel Capcl Boi, Villasimius, Sardinia, Italy, September 2-5, 1992

Tuesday, September 1, 1992

15:00-2O:OO Registratictn

19:30-2O:OO Welcome and Drinks

2cMlO Dinner

Wednesday, September 2, 1992

8: 15-8:30

. sessiun I:

8:30-&:%I

8:50-8:55

8:55-9z 15

9:S9:20

9:20-9:4O

9:40-9:45

9:45-lo:05

10:05-IO:10

lQ:lO-10:30

l&35- I 1 :Qcl

Introductory Remarks: M Hozumi, S Waxman

8:30-l&30 Cell Cycle Regulation and Cellular Senescence in Normal and Neoplastic Cells Chairmen: RW Craig/M Obinata

J C Barrett Cell Cycle Regulation and Cellular Senescence.

Discussion

D Levens The human c-myc FUSE element binds a differentiation regulated pro- tein with a novel sfructure

Discussion

F Tato Expression of my oncosene prevents muscle cell fusion, but not biocheni- cal differentiatim or commitment in the CZC12 myogenic cell line.

Discussion

A Skoultchi Pre-commitment gene expression changes during erythroleukemia cell differentiation

Discussion

Session Summary

Coffee Break

Session 2:

11:20-11;25

11:sII:45

11:45~1~:5cl

11:50-12:lO

12:10-12:15

12:15-12:35

12~3%12:40

12:ub13:OO

13:00-15:30

15:3O-17:OO

17:OO-2O:OO

17:OO-2O:OO

ll:OO-13:&l Differentiation Induction in the Treat- ment of Squamous Carcinomas Chairmen: R Lot&L De Luca

SH Yuspa, A Dlugosz The biochemical control of normal epidermal differentiation and altera- tions in neoplastic transformation.

Discussion

GR Cunha Role of kerarinocyte growth factor in androgen-dependent development of the neonatal mouse seminal vesicie.

Discussion

AM Jetten Modulation of growth and differentia- tion in human epidermal and tracheo- braonchial keratinocytes by interferon “f.

Discuss&t

SM Lippman Phase-II trial of 13-cis retinoic acid (13cRA) plus interferon-a (IFN) in locally-advanced squamous cell carci- noma (SCC) of the cervix.

Discussion

Session Summary

Lunch sod Afternoon Break

Poster Session Discussion

WoTkshops

Combined Sub-group ? and 3: Session Chairmen: RM Fried%xc/ D Levens

# 1 - Differentiation control in wwmal/ tran5formed epithelial cells

1. JC Barrett Cell cycle regulation and cellular senescence.

2. D Breitkreutz Differentiation in epidermal reconstituted tissues in vitro and in viva

3. G Sheikhnejad. C Marasco, j Sufrin, JK Christman Comparison of substrate specificity of mammalian

and bacterial CpG DNA methyltransferases [MTases].

4. R Nicholson, L Chen, JK Christman Effects of DNA methy!ation on hepatitis B virus (HBV) transcription and binding of CREB and CREB-like proteins to the HBV promoter.

5. VJ Cristofalo, RJ Pignolo, FL Cianciarulo, BR Di- Paolo, D Doggett, MC) Rotenberg Differential gene expression during senescence in culture.

6. GR Cunha, P Young, R Guzman, S Nandi Mesenchymal regulation of adult mouse mammary gland growth and differentiation.

7. LM De Luca Retinoic acid (RA) and P-carotene (Car) slightly en- hance papi!loma but strongly inhibit carcinoma for- mation on the skin of SENCAR mice.

8. H Jiang, Zz Su, J Lin, PB Fisher Gene expression changes induced in humar melanoma cells and SV40-immortalized human melanocytes exposed to differentiation inducing agents.

9. AM Jetten, NA Saunders, KW Marvin, MD George, W Fujimoro Regulation of gene expression during squamous cell differentiation.

10. M Takimoto, E Michelotti, M Matunis, M Michael, H Kruzsch, G Dreyfuss, D Levens A positive &-element of the human c-myc gene with homo-purine/homo-pyrimidine-like sequence binds proteins with unusual properties.

11. R Duncan, M Avigan, L Bazar, H Krutzsch, D Levens The human c-nrvc FUSE element binds a differen- tiation regulated protein with a novel structure.

12. R Lotan, SH Bemacki, J Pieniazek, EE Floyd, M George, AM Jetten Discovery of a new secreted protein marker of squamous differentiation (SqD), establishment of its relation to preprorelaxin and its regulation by reti- noids in rabbit tracheal epithelial (RbTE) cells.

13. DR Roop, JA Rothnagel, DS Bundman, MA Lon- gley, M Quintanilla, DA Greenhaigh Development of transgenic mouse models of skin carcinogenesis: potential applications.

14. M Crescenzi, F Taro Expression of nzvc oncogene prevents muscle cell fusion, but not biochemical differentiation or com- mitment in the C2CJ2 myogenic cell line.

15. SH Yuspa, A Dlugosz The biochemical control of normal epiderma! differ- entiation and alterations in neoplastic transforma- tion.

3# - Strategies for modifying gene expression during differentiation

28. A Ahmed, P J Higgins Induction of p52(PAI-1) gene expression and generation of the flat revertant phenotype in v-ras- transformed rat kidney cells by sodium butyrate.

29. JI Risinger, J Boyd DCC gene expression and function in neuronal differentiation.

30. W Brysch, K-H Schlingensiepen Proto-oncogene jrln-D acts as a functional tumor suppressor gene in fibrobiasts and mammary carci- noma cells.

31. G Raschella, A Negroni, T Skorski, S Pucci. M Nie- borowska-Skorska, A Romeo, B Calabretta !nhibition of proliferation by c-myb antisense RNA and oligodeoxynucleotides in transformed neuroec- todermal cell lines.

32. K Kenyon, S Contente, PC Trackman, J Tang, HM Kagen, RM Friedman A suppresor of the phenotypic expression of ras en- codes lysyl oxidase.

33. YKT Fung, B Driscoll. A T’Ang Structural homology between RB and P53 and the functional significance.

34. CC Harris, MC Hollstein, WP Bennett, IC Hsu, E Spillare and BI Gerwin ~53 Tumor suppressor gene involvement in human carcinogenesis.

35. A Kimchi, L Deiss, H Berissi Use of anti-sense knock-out approach for cloning new genes that suppress cell growth.

36. CW Miller, A Chumakov, A Also, DL Chen, HP Koeffler Transcriptional regulation by ~53 is modulated by oligomerization.

37. Z Mazouzi, C Fraucastel, M Castagna, J Robert- LezenCs Modulation of gene expression during anthracycline treatment of KS62 leukemia cells and doxorubicin- resistant K562 cells: relationship to growth inhibi- tion rmd erythroid differentiation.

38. KH Schlingensiepen, W Brysch Specific inhibition of different jun genes either in- hibits or stimulates cell differentiation.

39. L Szekely, W-Q Jiang, P Savatier, F Bulic-Jakus, V Wendel-Hansen, A Rosen, N Ringertz, G Klein, KG Wiman Involvement of the retinoblastoma (Rb) protein in the regulation of cell differentiation.

40. A T’Ang, B Driscoll, Y-K T Fung Regulation of phosphorylation of the retinoblastoma gene product.

41. AW Wood

42.

The ras oncogene as a therapeutic target.

A Yen, S Varvayanus Tumor suppressor gene expression responds tc chemotherapeutic drugs.

17:00-20:oo Sub-groltp 12: Session Chairmen: Y Yoshida/ G Francis

#12 - Clinical trials of differentiation therapy in he- matologic malignancies

158.

159.

160.

161.

162.

L Dcgos, S Castaigne, MT Daniel, P Fenaux Strkiegy for the treatment of acute promyelocytic levb mia combining differentiation agent and cy- totoAlc drugs.

R Gallagher, G Sagayadan, J Dutcher, P Wiemik Clonogenic assays support a trial of trans-retinoic acid (WA) therapy in accerated phase/early blastic crisis chronic myelogenous leukemia (CML- APiBC).

A Ganser, OG Ottmann, K Kolbe, A Maurer, S EIsner, G Geissler, C Schardt, R Reutzel, W Hid- demann, D Hoelzer All-trans retinoic acid (ATRA) and granulocyte colony-stimulating factor (G-CSF) in the treatment of myelodysplastic syndromes (MDS): A piiot study.

HT Hassan, HR Maurer Clinical trials of differentiation therapy in hema- tologic malignancies.

J Michaeli, M Andreef, R Stone, CL Young, D Kufe, RA Rifkind, PA Marks Phase II clinical trial with hexamethylene bisacetamide (HMBA) in myelodysplastic syn- drome (MDS) and acute myelogenous leukemia

._ (AML),

163. R Ohno, H Yoshida, T Naoe, T Ohshima, H Dohi, N Endo, T Fujimoto, T Kobayashi, A Hiraoka. Y Kodera, M Hirano and Koseisho Leukemia Study Group. Remission induction therapy of refractory acute promyelocytic leukemia (APL) with all-tram ret- inoic acid (ATKA).

164. W Piacibello, F Sanavio, L Fubini, S Morelli, A Severino, A Stacchini, M Aglietta Effect of recombinant human stem cell factor on the proliferation and differentiation in vitro of hemopoietic progc:qitors in myelodysplastic syn- dromes.

165. A Pinto, D Aldinucci, V Gattei, V Zagonel, G Tor- tora, A Budillon, YS Cho-Chung Inhibition of the self-renewal capacity of blast pro- genitors from acute myeloblastic leukemia (AML) patients by site-selective 8-chloro-cyclic adenosine

166.

167.

168.

169.

170.

171.

172.

III

3’, 5’ monophosphate (S-Cl-cAMP): a new approach for differentiation therapy of AML in humans.

V Zagonel, A Pinto, G Lo Re, V Gattei, D AI- dinucci, S Monfardini S-aza-2’-deoxycytidine (Decitabine) is an effective agent for differentiation therapy of advanced my- eIGdysplastic syndromes (MDS).

HD Preisler, A Raza, R Larson The proliferative rates of acute myelogenous leukemia cells can be accelerated or slowed in vivo in patients.

A Rosen, V Wendel-Hansen M CarIsson, K Nilsson Induction of growth and differentiation in B-type chronic lymphocytic leukemia (B-CLL) cells by cytokines and thioredoxin.

MA Smith, PC Adamson, FM Balis, L Aronson, RF Murphy, KA Godwin, J Feusner, GD Ham- mond, DG Poplack Phase 1 and phannacokinetic avaluation of all- tram retinoic acid in pediatric patients and phar- macokinetic evaluation in the nonhuman primate.

NG Testa, L Coutinho, J Chang, G Morgenstem, H Scarffe, TM Dexter Differences in behaviour between AML and nor- mal cells in long-term bone marrow culture used for a therapeutic approach.

RP Warrell JR, S Frankel, WH Miller Jk, 5 Muindi, C Young, E Dmitrovsky Clinical and pharmacologic aspects of all-trans retinoic acid treatment in acute promyelocytic leukemia.

Y Yoshida, S Oguma, H Uchino, T Maekawa. T Nomura Randomized trial of alfacalcidol in the myelody- splastic syndromes.

Thursday, September 3, 1992

Session 3:

8:30-8:SO

8:50-8:55

8X55-9:15

9:15-9:20

9:20-9:40

8:30-lo:30 Tumor Suppressor Genes and Cancer Control Chairmen: YK Fung/CC Harris

CC Harris p53 tumor suppressor gene involve- ment in human carcinogenesis

Discussion

C Croce Protein tyrosine Phosphatases

Discussion

M Oishi The role of protein phosphorylation and dephosphorylation at tyrosine re- sidues in cellular differentiation

IV

9:40-9:45

9:4s-10

P0:0s-10:10

lc:lo-10:30

10:30-lo:35

10:3s-11:oo

Session 4:

11:00-l 1:20

11:20-11:2s

11:25-11:4s

11:45-11:50

11:50-12:lO

12:10-12-1s

12:15-12:35

12:35-12:40

I2:40-13:OO

13:00-15:30

15:30-17:oo

17:00-2O:OO

17:00-2O:OO

Discussion

AW Wood The ras oncogene as a therapeutic tar-

get Discussion

C Chomienne Regulation of Bcl-2 and cell death by all-rruns retinoic acid in acute promy- elocytic leukemic cells.

Discutsion

Coffee Break

11:00-1390 APL - a model or a unique condition for differentiation therapy? Chairmen: R Ohno/S Waxman

AJ Kakizuka PML RAR, A fusion protein in human acute promyelocytic leukemia

Discussion

A Zelent Novel chimeric mRNA expressed in APL patient with a variant t( 11;17) re- ciprocal chromosomal translocation between RAR-a and previously un- characterised TFIIIA-like zinc-finger encoding gene on chromosome 1 lq.

Discussion

RP Warrell JR Clinical and pharmacologic aspects of all-rruns retinoic acid treatment in acute promyelocytic leukemia.

Discussion

P Fenaux Strategy for the treatment of acute promyelocytic leukemia combining differentiation agent and cytotoxic drugs.

Discussion

Session Summary

Lunch and Afternoon break

Poster Session and Discussion

Workshops

Combined Sub-group 2 and 4 Session Chairmen: M Oishi/ A Skoultchi

#2 - Differentiation control in hematopoiktic cells

16. I Blazsek, XH Liu, Ph Quittet, A Anjo, M Reynes, M Comisso, JL Misset Isolation and comparative analysis of the Hematon and the cubbleston area forming cells reveal ho-

17.

18.

19.

20.

21.

mologous functional units in the human or murine bone marrow.

RW Craig, KM Kozopas, T Yang, HL Buchan, P Zhou Characterization of m&-i, a gene expressed in the early stages of myeloid leukemia cell differentia- tion.

T Peled, M Rigel, AJ Traves, V Barak, E Fibach The effet of M20 IL-I inhibitor on the proliferation and differentiaiion of human hemopoietic cells.

T Watanabe, T Fume, K Konno. M Oishi The role of protein phosphorylation and dephospho- rylation at tyrosine residues in cellular differentia- tion.

S Ottolenghi, AR Migliaccio, S Crotta, C Bertini, C Barron, A Ronchi, S Nicolis, GL Quintini. N Ko- matsu, Y Jiang, M Baiocchi, L Ruzzi, G Migliaccio, JW Adamson Expression of the transcription factor GATA-1 and of erythropoietin receptor in growth factor depend- ent erythroid and non-erythroid cell lines.

U Testa, E Pelosi, M Gabbianclli, C Fossati, S Campisi, G Isacchi, G Mastroberardino, C Peschle Cascade transactivation of growh factor receptors in early hematopoiesis.

22. M Valtieri, U Testa, P Samoggia, M Gabbianelli, G Isacchi, A Camagna, C Peschle Pure human hematopoietic progenitors in liquid culture: A model for selective/synchronized differ- entiation along the erythoid or granulomonocytic lineage.

23. A Raza, P Kadam, H Preisler Cytokines,/stromal cells in hematopoietic microen- vironment influence proliferation/differentiation of acute myeloid leukemia cells.

24. EM Coccia, V Profita, G Fiorucci, G Romeo, E Af- fabris, U Testa, MW Hentze, A Battistini, GB Rossi Modulation of ferritin H-chain expression in Friend erythroleukemia cells: transcriptional and trans- lational regulation by hemin.

25. G Saglio. C DZamascheiia, A Guerrasio. A Alfarano, C Rosso, A Biondi, A Pambaldi, S Nicolis, S Ot- tolenghi Expression of the erythroid-specific transcription factor GATA-1 in human myeloid leukemic cells.

26. A Skoultchi, G Cheng, D Krimer, G Rao, C Austin Precommitment gene expression changes during mouse erythroleukemia cell differentiation and their relationship to c-myc.

27. Y Yoshida, N Anzai, T Hirama, H Kawsbata, H Masutani Cell death and differentiation in human myeloid leukemia cells.

#4 - Strategies for modifying gene expression during hematopoietic differentiatbn

#13 - Clinical trials of differentiation therapy of solid tumors

43. NC Nicolaides. I Correa, C Casadevall, S Travali, KJ Soprano, B Calabretta JUND transactivates reporter gene expression driven by c-myb promoter via and Apl-like element.

T Skorski, C Szczylike, MZ Ratajczak, L Malaguarnera, AM Gewirtz, B Calabretta Growth factor-dependent inhibition of normal he- matopoiesis by N-ras antisense oligodeoxynu- cleotides.

173.

44.

45.

46.

47.

48.

49.

5th

174.

L Bonhomme, G Fredj, S Averous, AM Szekely, I Blazsek. E Ecstein, B Trumbic, P Meyer, C Fambos. C Jasmin, JL Misset Topical and systemic treatment of Kaposi’s sar- coma with all-@ans.retinoic acid.

B Conley, S Wu, M Egorin, S Hodges, D Van Echo Phase I trial of truns-retinoic acid (TRA) in solid tumor patients (pt).

H Garewal C Chomienne, S Barbey, N Balitrand, L Degos, L Sachs Regulaiion of Bcl-2 and cell death by all-tram ret- inoic acid in acute promyelocytic leukemic cells.

MZ Ratjczak, S Luger, N Hijiya, B Calabretta, A Gewirtz Therapeutic utility of antisense (AS) oligodeoxynu- cleotides in vitro and in viva.

A Kimchi, D Melamed, D Resnitzky, N Teifenbrun, N Levy, D Zafriri Interleukin-6 modifies cell cycle controlling nuclear proteins in Ml myeloblastic cells.

M Lu, N Zhang, A Ho The TCL3 (HOX-11) proto-oncogene is a cell-type- specific regulatory factor in the hematopoietic sys- tem.

Y Nemoto, TK Tsttji, T Yamamoto. S Takada, Y Matsui, M Obinata Antisense RNA of the latent period gene (MERS) inhibits erythroleukemic differentiation.

Y Ohmori, J Tanabe, M Terashima, Y Nemoto, W Shoji, S Takada, M Obinata Role of c-myc on erythroleukemic differentiation.

51. HD Preisler, V Gopal, SD Banavali, A Raza Alteration of myb and ntyc expression in acute my- elogenous leukemia cells (AML) in vivo in patients.

52. Y Furukawa, M Ohta, A Tsunoda, JD Griffin, M Saito Transforming growth factor-6 (TGF-B) inhibits phosphorylation of the retinoblastoma susceptibility gene product in human monocytic leukemia cell line JOSK-I.

53. A Skoultchi, G Cheng, Y Dong, D Liu, A Sirotkin Induction of Hl histone gene expression during mouse erythroleukemia cell differentiation.

54. JB Weinberg, SN Mason, TS Wortham, DA Nntter JR. Dissociation of functional monocytic differentiation of myeloid leukemia ceils frtim monokine mRNA and protein expression by the use of pentoxifylline and dexamethasone.

17:00-20:00 Sub-group 13: Chairmen: SM Lippman/FL Meys- kens, Jr.

V

175.

176.

177.

178.

179.

180.

181.

182.

183.

184.

185.

Oral cancer prevention studies.

H Garewal, Richard Sampliner and Brian Fennerty Upper GI tract premalignant lesions: Barrett’s esophagus and gastric intestinal metaplasia.

WN Hittelman, W Ahn, EC Silva, S Lippman, JL Kavanagh, M Paredes-Espinoza, WK Hong, IH Krakoff In situ analysis of human cervix cancer to 13-cis retinoic acid and alpha interferon.

SM Lippman, JJ Kavanagh, M Paredes, WK Hong, R Lotan, H Hua, W Hittelman, E Holdener, IH Krakoff Phase-II trial of 13-cis retinoic acid (13cRA) plus interferon-o! (IFN) in locally-advanced squamous cell carcinoma (SCC) of the cervix.

R Lotan, J Clifford, W Hong, C Zou Modulation of differentiation and growth of squamous carcinoma cells in vitro by retinoids.

FL Meyskens JR, DT Yamanishi, JA Buckmeier, MJ Graham, JE Voboril Expression of the retinoic acid receptors and effect of retinoic acid on human primary neonatal melanocytes and metastatic melanoma cell strains.

G Sozzi, M Miozzo, CT Cariani, E Tagliabue, U Pastarino, S Pilot& G Del!a ?crta. MA Pierotti Analysis of genetic changes in non malignant bronchial epithelium, preneoplastic lesions and lung cancer.

U Pastorino, N Van Zandwijk, N DeVries, 0 Dalesio, M Infante, M Maioli, M Valente, G Ravasi European chemoprevention hiah in patients with lung cancer or head and neck cancer, using high dose retinol palmitate (RP) and N-acetyl-cysteine (NAC). Z Reiter, MW Taylor Possible roles for interferon-a in remiSSiOn of

AIDS-related Kaposi’s sarcoma.

H Ross, J Voboril. J Buckmeier All trans-retinoic acid inhibits the growth of human lung cancer cells and alters CytOkine Pm-

duction.

M Takase, H Yoshida, M Sat0 Induction of cells with phenotypic features of

smooth muscle ceils by treatment with DNA to- poisomer2se I inhibitor, etoposide, in a neoplastic human saiivary intercalated duct cell line.

186. N Sidell, L Bhatti Transcriptional up-regulation of interleukin-2 re- ceptors by retinoic acid is mediated by interactions with negative regulatory elements in the inter- leukin-2-receptor promoter.

Friday, September 4,

Session 5:

8:30-8:50

8:50-8:55

8:55-9:15

9:15-920

9:20-9:40

9:40-9:45

9:45-lo:05

10:05-IO:10

lO:lO-10:30

l&30-11:oo

Session 6:

ll:OO-1l:SO

11:20-Ii:25

11:25-11:45

6:30-IO:30 Is There an Anti-Sense Strategy for a Selective Differemiation Therapy of Cancer? Chairmen: H Preisler/B Calabretia

A Kimchi Use of anti-sense knock-out approach for cloning new genes that suppress cell growth.

Discussion

M Obinata Antisense ?NA of the latent period gene (MERS) inhibits ery- throleukemic differentiation

Discussion

B Calabretta Growth Factor - dependent inhibition of normal hematopoiesis by N-ras an- tisense oligodeoxynucleotides

Discussion

YS Cho-Chung Suppression of growth of human colon carcinoma in athymic mice by antisense oligodeoxynucleotides against type 1 regulatory subunit of &AMP-dependent protein kinase.

Discussion

Session Summary

Coffee Break

11:00-13-00 Growth Control and Differentiation Factors Chairmen: I Blazsek/ R Revoltella

C P,=):& Cascade transactivation of growth fac- tor receptors in early hematopoiesis.

Discussion

HE Broxmeyer Suppressive effects of human proin-

11:45-11:50

11:5c)-12-10

12:10-12:15

12:15-12:35

12:35-12:40

12:40-13:oo

15:00-17:oo

17:00-20:00

17:00-20:00

flammatory cytokices on proliferation of human myeloid progenitor cells.

Discussion

A Raza Effects of retinoic acid, interferon and granulocyte-macrophage colony stimulating factor on human leukemic cells and the hematopoetic microen- vironment in vivo.

Discussion

A Amsterdam Introduction of a gonadotropin recep- tor gene to immortalized granulosa cells leads to reconstitution of hor- mone-dependent steroidogenesis and suppression of cell growth.

Discussion

Session Summary

Poster Session and Discussion

Workshops

Combined Sub-group 5 and 7: Chairmen: N Tests/ML Levitt

57. J DiPersio, P Doshi, A Rapoport, J Vent:palli Structural interactions of the GM-CSF/IL-3 receptor complex.

58.

59.

60.

E Fibach, T Peled, EA Rachmilewitz The potential of human myeloid leukemic cells to undergo <<spontaneous> differentiation in vitro and their response to differentiation-inducing-agents.

E Fibach, EA Rachmilewitz Stimulation of erythroid progenitors by high con- centrations of erythropoietin results in normoblasts arrested in G2 phase of the cell cycle.

M Hashimoto, Y Eto, R Yamada, M Muramatsu Neural differentiation is regulated by the interaction of activin and follistatin.

61.

62.

J Okabe-Kado, M Hozumi Identity of differentiation inhibiting factor for mouse myeloid leukemia cells with Nm23/Nu- cleoside diphosphate kinase.

ML Levitt, W Ferri, J Mayotte, P Kane, T Fitz, A Gazdar, K Stromber, EA Sausville

#5 - Regulatory growth and differentiation factors

55. W Brysch, U Bogdahn, C Behl, KH Schlingensie- pen Suppression of growth factor gene expression with antisense DNA - A novel approach to tumor growth modulation.

56. ET Alarid, GR Cunha, J Rubin Role of keratinocyte growih factor in androgec-de- pendent development of the neonatal mouse seminal veiscle.

63.

64.

65.

The role of the epidennal growth factor receptor (EGFR) in squamous differentiation of human lung cancer cell tines.

N Yanai, 0 Ohneda. M Obinata In vitro reconstruction of erythropoietic microen- vironment by the established stromal cells.

P Beffy, P Rovero, V Di Bartolo, L Trombi, L Laric- chia, RP Revoltella Structure-function analyses of human granulocyte- macrophage colony stimu!ating factor using syn- thetic peptides and antibodies.

K Takeda, M Iwanami, S Kumakura, S Iwamoto, T Tsuji, A Miyama Enterotoxin, an ADP-ribosylation toxin, remarkably enhances TNF-induced differentiation of human myeloblastic leukemia ML-I cells.

66. M Grossi, S Russo, SA LaRocca, M Crescenzi, A Zanetti, G Falcone, S AYema, F Tato Expression and activity of muscle regulatory factors in normal and transformed muscle cells.

67. A Yuo, E Azuma, S Kitagawa, T i:asahara, K Matsushima, M Saito, F Takaku Stimulation and priming of human neutrophils by interleukin 8: cooperation with tumor necrosis fac- tor and colony-stimulating factors.

# - Biological modification as a response to differ- entiatiora therapy

81.

82.

83.

84.

85.

86.

BS Sub, L Eisenbach, A Amsterdam Cyclic AMP suppresses metastatic spread in nude mice of steroidogenic rat granulosa cells trans- formed by SV40 and Ha-ras oncogene.

HE Broxmeyer, B Sherry, S Cooper, L Lu, R Maze, MP Beckmann, A Cerami, P Ralph Suppressive effects of human proinflammatory cy- tokines on proliferation of human myeloid progeni- tor cells.

C Chany, F Chany-Foumier, P-H .!iang Interferon (IFN) and sarcolectin in the regulation of growth and differentiation.

RI Freshney, C McCormick, V Speirs Regulation of differentiation in lung carcinoma: paracrine control by glucocorticoids and lung fibro- blasts.

S Shimada, J Schlom, M Ogawa, John W Greiner Molecular and biological characteristics of a poten- tially novel human gastric tumor antigen.

Y Honma, M Hozumi Herbimycin A, an inhibitor of tyrosine kinase pro- longs survival of mice inoculated with myeloid leukemia Cl cells with high expression of v-abl ty- rosine kinase.

87. AM Jetten, NA Saunders, MD George Modulation of growth and differentiation in human

epidermal and tracheobronchial keratinocytes by in- terferon y

88. M Revel. N Haran-Ghera, A Katz, L Eisenbach, M Feldman, S Slavin Antitumor effects of human m-6 in murine leukemia and sohd tumor models.

89. M Revel, S Harroch, Y Gothelf, J Chebath Differentiation of myeloleukemic Ml cells: role of early gene activations by IL-6 and IFN.

90. Z Reiter, S Klein, MW Taylor Encapsulation of interferons in liposomes increases their biological activities.

91. E Wickstrom, TA Bacon, KS CraB Impact of anti-c-myc DNA on differentiation and MHC class 1 antigens of leukemic cel!s.

17:00-20:00 Combined Sub-group 9 and 10: Chairmen: E Schwartt/L Gudas

#9 - Pharmacology and mechanism of action of differentiating agents

117. GE Francis

118.

Theoretical and practical considerations in high- throughput screening for differentiation agents.

HM Beere, Ri Mormoto, CM Waters, R Parmar. JA Hickman Changes in the levels of constitutively expressed but not stress-induced heat shock proteins during terminal differentiation of HL-60 human leukemia cells.

lP9.

120.

121,

J Michaeli, RN Kolesnick, X Busquets, PA Marks, R Rifkind Hexamethylene bisacetamide (HMBA)-induced re- duction in diacylglycerol levels is associated with differentiation of murine erythroleukemia cells.

E Ohih, B Csdkay. J Papp Modulation of gene expression through inhibiting guanylatc metaholism.

A Raza, H Preisler Effects of retinoic acid, interferon and granulo- cytic-macrophage colony stimulating factor on human leukemic cells and the hematopoiztic mi- croenvironment in vivo

122.

123.

EL Schwartz, H Chamberlin, P Ravichander, JA Whitbread Inhibition of the binding of granulocylc. :‘?1crO- phage colony stimulating factor (GM-CSF) and in- sulin to human leukemia cells by the differentiation inducer dimethylsulfoxide.

Y Yamaji, T Shiotani, Y Hashimoto, J Fujita, K Ikeda, T Tanaka, J Takahara, S Irino Reversal of enzymic phenotype of thymidine me-

VIII

124. MW Taylor, A Yeivin I36

125.

Sodium butyrate induces transcription of pro- moters adjacent to a virti enhancer sequence.

C Trentesaux. M Ngo Nyoung, A Aries, A Ronchi, S Ottolenghi. JC Jardillier, P Joannesson Expression of GATA-1 and NFE-2 erythroid- specific transfactors during aclacinomycin-medi- ated differentiation of human erythroleukemic cells.

137.

138. 126.

127.

IE Christou, AS Tsiftsoglou Analysis of the developmental regulation of RNA stability in differentiating murine erythroleukemia (MEL) cells with the use of a cell free system.

IS Pappas, AS Tsiftsoglou Detection of receptor-like proteins for [2-(3-ethy- lurcido)-6-acetylamino-pyridlne] (‘JDP), a: i? ducer of differentiation in murine erythroleukemia (MEL) cells.

139.

140.

141.

142.

143.

144.

145.

tabolism in induced differentiation of leukemia cells.

128. J Hsriguchi-Yamada, H Yamada Altered expression of cell cycle-related genes during the differentiation induced by TPA or DMSO in HL60 cells.

#lO - Novel differentiation inducers

129. YS Cho-Chung, A Budillon, T Clair Role of type 1 regulatory subunit (RI) of CAMP dependent protein kinase (PKA) in multidrug re- sistance (mdr) of cancer cells.

130. _YS Cho-Chung, T Clair, S Meissner

131.

132.

133”

134.

13s.

Suppression of growth of human colon carcinoma in athymic mice by antisense oligodeoxynu- cleotides against type 1 regulatory subunit of CAMP-dependent protein kinase.

R Emmons. K Teelmann, M Klaus, J Eliason RO 40-8757, a new aretinoid with antitumor ac- tivity in vivo and in viiro.

A Dlugosz, JE Strickland, H Hennings, SH Yuspa The protein kinase inhibitor staurosporine induces differentiation of necplastic mouse keratinocytes in vitro and block; their growth as benign epider- mal tumors in vivo.

GE Francis, D Fisher, C Delgado, M Domine, F Malik, OP Smith, MC Tejedor Peg-cytokines: Improved pharmaceutical proper- ties and dissociation of individual bioactivities.

MC Tejedor, C Chresta, J Berney, C Delgado, GE Francis Stimulatory and inhibitory e:fects of DNA to- poisomerase II (TOP0 II) inhibitors on colony for- mation of human bone marrow progeniior celis.

YK Jing, J Han Cell differentiation of HL-60 cells induced by Bo-

swellic acid (BC4), an active principle, from Bo- swellia cartorii Birdw.

J Han, Y Lu, QM Gu Pharmacological studies and clinical application of N-4-(carboxyphenyl) retinamide (RI]) for the treat- ment of premalignancies.

E Huberman, K Kiguchi, C Chubb, C Giometti, H Fujiki Differentiation control in human breast tumor cells by okadaic acid and related pbosphatase inhibitors.

MR Maurer. P Hilgard In vitro anticancer drug screening using differen- tiation assays.

S Nakai, K Aihara, K Kawai, K Ogino, F Saitou, M Sato, M Adachi Differentiation-inducing activity of 3,4-dihydro-6- [4- (3,4-dimethoxybenzoyl)-l-piperazinyl]- 2 (1H) - quinolinone (vesnarinone) against human leukemia and solid tumor cells.

M Izawa, S Takayama, N Shindo-Okada, S Doi, M Kimura, M Katsuki, S Nishimura Inhibitiou of chemical carcinogenesis in vivo by azatyrosine.

WJ Kryzosiak, N Shindo-Okada, H Teshima, K Nakajima, S Nishimura Genes specifically expressed in flat revertant cells derived from rus-transformed cell by the treatment with azatyrosine.

K Tsuneizumi, K Kondo, T Watanabe, M Oishi Induction of in vitro differentiation of mouse embryonal carcinoma (F9) cells by inhibitors of topoisomerases.

Y Kasai, H Yoshida, M Sato Effects of S-fluoro-2’-deoxyuridine-S-mono- phosphate on morphological features and biologi- cal markers of a neoplastic human salivary intercalated duct cell line grown in culture and as xenograft in nude mouse.

JB Weinberg, GC Magrinat, SN Mason, PJ Shami Induction of monocytic leukemia cell differentia- tion by nitric oxide, a stromal cell-derived, non- protein growth-inhibiting molecule.

D Samid Phenylacetate - A novel nontoxic inducer of tumor cell maturation.

18:30-20:00 Sub-group 11: Chairmen: M Hozumi/S Waxman

#Ill - Design of combination differentiation therapy

146. D Plehn-Dujowich, I Keren-Tal, BS Suh, A Dantes, A Amsterdam Suppression of growth and induction of differen- tiation of oncogene-transformed granulosa cells

147.

148.

149.

150.

151.

152.

153.

154.

155.

upon synergistic action of CAMP and dexametha- sone.

I Blazsek, P Quittet, XH Liu, M Comisso, C Farabos, E Goldschmidt, JL Misset Ro1es for the heliodynamic hormones, la, 25di- hydroxyvitamin D3 and retinoids, in control of normal and malignous hematopoiesis.

R He, TR Breitman Combinations of 24, 24difluoro-la, 25dihydroxy- vitamin D3 and either retinoic acid, sodium butyrate, dimethyl sulfoxide, or hexamethylene bisacetamide synergistically induce monocytoid differentiation of the human myeloid leukemia cell line I-&60.

A Budillon, T Clair, YS Cho-Chung 8Cl-CAMP acts synergistically with tumor necro- sis factor (TNFa), TGFP, or retinoic acid (RA) in growth inhibition and differentiation of human leukemia and lymphoma cells.

B Conley, S Wu, S Pan, M Egorin The effect of hexamethylene bisacetamide on the activity of DNA-interactive agents in human colon cancer cell lines.

H Jiang, SZ Su, 3 Boyd, PB Fisher Multistep model of terminal differentiation in human melanoma cells treated with the combina- tion of recombinant human fibroblast interferon (IFN-j3) and mezerein (MEZ).

Y Fujii, M Imamura, S Hashino, H Kobayashi, M Kobayashi, M Kasai, K Sakurada, T Miyazaki Therapy with cytokines and biological response modifiers (BRMs) prior to syngeneic bone marrow transplantation in mice. Effect of recombinant human interleukin-1 p (rhIL- 1 p), interleukin-2 (rhIL-2). interleukind (rhILd), recombinant murine tumor necrosis factor a (rmTNF a), and Chinese herbal medicine, ninjin-youei-to (NYT) on immunohematologtic reconstitution.

JW Greiner, C Nieroda, C Dansky-Ullmann, J Schlom Improved antitumor efficacy of a radiolabeled monoclonal antibody when combined with inter., feron-gamma.

T Nakamaki, N Tsuruoka, Y Honma. M Hozumi Effect of granulocyte-macrophage colony-stimu-

lating factor on monocytic differentiation of acute promyelocytic leukemia cells in primary culture.

Zvi Reiter, S Tomson, MW Taylor The effects of combination treatment of interferon- a and 2Chlorodeoxyadenosine on hairy-cell leukemia-like cell line.

156. PJ Tofilon, EA Mendoza, E Vrdoljak, CA Bill Enhancement of tumor cell killing in virro by com- binations of aclacinomycin A and radiation.

157. G Weber Tiazofurin (TR) treatment induced differentiation in patients with chronic granulocytic leukemia in

Ix

blast crisis (CGL-BC) and was synergistic in HL- -63 cells with ribavirin (RB), retinoic acid (RA) and gemcitabine (DFDC).

Saturday, September 5

Session 7: 8:30-l&30

8:30-8%

Identification and Treatment of Reti- noid Aberrations in Neoplasia Chairmen: R Lotan/T Breitman

WH Miller Jr Cross-coupling between the retinoic acid (RA) and protein kinase C (PKC) pathways potentiates R&mediated human teratocarcinoma (TC) differen- . . kt:iGn

8:50-8-55 Discussion

8-5%9~15 CJ Thiele

9:15-9:20

9:20-9:40

9:40-9:45

9:45-l&05

l&05-IO:10

l&10-10:30

10:30-1l:OO

Session 8:

Coordinate regulation of oncogenes, suppressor genes and cell cycle genes in human neuroblastoma ceil lines sensitive to retinoic acid and its dis- ruption in NB cells constitutively ex- pressing IGG-11.

Discussion

LJ Gudas Abnormal expression of Ttinoic acid receptors and keratin 19 by human oral and epidermal squamous cell car- cinoma cell lines.

Discussion

R Emmons Ro 40-8757, a new arotinoid with an- titumor activity in vivo and in vitro .

Discussion

Session Summary

Coffee Break

lI:OO-13:OO

11:00-l I:20

11:20-l l-25

1::25-11-45

11:45-l 1:50

Development of Clinically Useful Differentiation Inducers Chairmen: P Calabresi/S Nishimttra

DR Parkinson All-truns retinoic acid drug develop- ment at the National Cancer ?nStitUte (NCI).

Discussion

M Dawson Effect of retinoids on the anchorage- independent growth of JBS epidetmal cells

Discussion

X

11:50-12:lO G Weber

12:10-12:15

12:15-12-35

Tiazofurin (TR) treatment induced differentiation in patients with chronic granuiocfiic leukemia in blast crisis (CGK-BC) and was synergistic in HL- 60 cells with ribavirin (RB), retinoic acid (RA) and gemcitabine (DFDC).

Discussion

D Samid

12:35-12:40

12:40-13:OO

15:30-17:oo

17:00-20:00

17:00-20:00

Phsnylacetate - A novel nontoxic in- duce: of tumor cell maturation

Discussion

Session Summary

Poster Session and Discussion

Workshops

Sub-group 8 Chairmen: H de The/R Gallagher Sub-group 8A Chairmen: C Chomiene/C Young

#8 - Normal and abuormal retinoic acid metabolism in growth and differentiation

92. PC Adamson, FM Balis, MA Smith, RF Murphy, Kh Godwin, JF BoyIan,. LJ Gudas, DG Poplack Capacity-limited metabolism of all-frans-retinoic acid and the time course of enzyme induction in the non-human primate.

93. JS Berrram, MZ Hossain, LX Zhsng, H Guo Retinoids up-regulate expression of connexion 43 in human and mouse cells: implication for growth control and differentiation.

94. N Takahashi, C Liapi, WB Anderson, TR Brcitman Retinoylation of the CAMP-binding regulator;l subunits of CAMPdependent protein kinases in HL-60 cells.

95. CJ Rudd, K Suing, MI Dawson Effect of retinoids on the anchorage-independent growth of JB6 epidermal cells.

96. L Hu: DL Crowe, JG Rheinwald, P Chambon, LJ Gudas Abnomlal expression of retinoic acid receptors and keratin 19 by human oral and epidermal squamous cell carcinoma cell lines.

97. AW Lan@ton, LJ Gudas Identification of a retinoic acid responsive enhancer 3’ of the murine homeobox gene Hox-1.6.

98. J Muindi, C Young Catabolism of all-rrans-retinoic acid by human cell microsomes selectively enriched in specified cy- tochrome P-450 enzymes.

99. J Muindi, C Young, J Rigas, P Francis, M Kris, H Scher, WK Kelly, R Warrell Jr. Studies on the bioavailability of orally administered all-truns-retinoic acid in cancer patients; its modu- lation by ketoconazole.

100.

101,

102.

# 8A

103.

104.

105.

106.

107.

108.

109.

110.

JL Napoli, PD Fiorella. MHEM Boerman, KC Posch Functions of retinoid binding proteins in maintain- ing retinoic acid homeostasis.

JP Stein, JS Gilsdorf, TA Burrell, MJ Hozza Structural/Functional analyses of a retinoic acid regulated promoter.

CJ Thiele, C Gaetano, K Matsumoto Coordinate regulation of oncogenes, suppresor genes and cell cycle genes in human neuroblas- toma cell lines sensitive to retinoic acid and its disruption in NB cells constituvely expressing IGF-Il.

SJ Chen, Z Chen, H-H Tong, A Chen, ZY Wang, M Le Coniat, R Berger, AZ Zelent, S Waxman The retinoic acid receptor alpha (RARA) gene is fused with a transcription unit on chromosome 1 lq in an acute promyeleocytic leukemia (APL) patient with variant t(l1;17) translocation.

Z Chen, SJ Chen, GL Sun, XS Li, JR Cai, ZY Wang Is acute promyelocytic leukemia (APL) a homo- genous disease?

C Chomienne, F Frazhanet, M Comic, P ROUS- selot, S Castaigne, L Degos, H de The, P Lefebvre, N Balitrand Function of normal and altered retinoic acid bind- ing proteins in acute promyelocytic leukemia.

A Dejean, C Lavau, C Chomienne, A Marchio, L Degos, H de The The t( 15; 17) translocation of acute promyelocytic leukemia generates a structurally altered retinoic acid receptor.

A Dejean, C Lavau, C Chomienne, A Marchio, L Degos, H de The The t(l5;17) translocation of acute promyelocytic leukemia generates a functionally altered retinoic acid receptor.

H de The, Cc Lavau, C Chomienne, A Marchio, L Degos, A Dejean PML: a new zinc finger protein involved in the t( 1 5,17) translocation of acute promyelocy tic leukemia.

R Gallagher, A Zelent, S Zhang. S Peng, S Rao, G Sagayadan, S Waxman, P Wiemik Differential regulation of PML-RARa and RARloll mRNAs following trans-retinoic acid (rkri, . ,I!- ment of acute promyelocytic leukemia (APL):, cells.

FR Grignani, PP Pandolfi, M Alcalay, M Fagioli, A Mencarelli, F Grignani, PG Pelicci Molecular genetics of the t(l5;17) of acute pro- myelocytic leukemias (APL).

111.

112.

113.

114.

115.

116.

C Nervi, EE Poindexter, F Grignani, PP Pandolfi, PG Pelicci, AIM Jetten Characterization of the acute promyelocytic leukemia (APL) specific t(15;17) PML-RARu chimeric product.

A Kakizuka, JA Dyck, RM Evans PML-RAR, A fusion protein in human acute pro- myelocytic leukemia.

WH Miller, Jr, A Kakizuka, SR Frankel, RP Warrell, Jr, A DeBlasio, Z Arlin, RM Evans, E Dmirrovsky Reverse transcription polymerase chain reaction (RT-PCR) for the rearranged retinoic acid mcep- tor-c% (RAR-@predicts response of acute promy- elocytic leukemia (APL) to retinoic acid (RA) therapy and detects minimal residual disease.

A Zelent, SJ Chen, Z Chen, N Brand, JH Tong, JP Geng, HQ Yu, A Chen, S Waxman Novel chimeric mRNA expressed in APL patient with a variant t(l1;17) reciprocal chromosomal translocation between RAR-or and previously un- characterized TFIIIA-like zinc-finger encoding gene on chromosome Ilq.

DR Parkinson, HC Stevenson, MA smith, BD Che- son and MA Friedman All-trans Retinoic Acid Drug Development at the National Cancer Institute (NCI).

PT van der Laag, CE van den Drink, T ijbart, L Kwakonber, DJ lran der Leede, T Opdenoordt, SW de Laat, B van den Burg Resistance to retinoic acid and nuclear receptors for retinoic acid in human renal all carcinoma and breast carcinoma cell lines: possible role as tumor suppressor genes in kidney and breast cancer.

17:00-18:30 Sub-group 6: Chairmen: E Huberman/M Saito

#6: Membrane events regulating differentiation and terminal cell divbim

68. BS Suh, R Sprengel, I Keren-Tal, S Himmelhoch, A Amsterdam Introduction of a gonadotropin receptor gene to im- mortalized granuiosa cells leads to reconstitution of hormone-dependent steroidogenesis and suppres- sion of cell growth.

69. F Calvo. G Millet, A Degeorges, P de Cremoux, M Boiron Interactions between breast normal stroma and breast epithelial cells.

70. A Frczouls, T Lesuffleur, M Castagna Expression of protein kinase C isoforms in human colon carcinoma cells HT-29 as related to cell differentiation.

71. GR Cunha, P Young, R Guzman, S Nandi. W Im- agawa, J Rubin

72.

Growth-promoting paracrine effects of preputial gland mesenchyme on adult mouse mammary epithelial cells: Role of keratinocyte growth factor.

J DiPersio, C Abboud, S Aggarwal, D Golde GM-CSF directly induces neutrophil platelet acti- vating factor (PAF) and leukotriene B4 (LTB4) syn- thesis: activation of the LtysoPAF acetyltransferase through a tyrosine kinase-dependent signaling cas- cade.

73. J DiPersio, S Luhowskyj Identification of novel tyrosine (Y) and serine/threonine (S/T) kinases in resting and acti- vated human stem cells.

74. J Kurie, A Younes, WH Miller, Jr, R Kolesnick, E Dmitrovsky Cross-coupling between the retinoic acid (RA) and protein kinase C (PKC) pathways potentiates RA- mediated human teratocarcinoma (TC) differentia- tion.

75.

76.

77.

G Hangoc, R Daub, RG Maze, HE Broxmeyer, MA Harrington Enhanced proliferation and differentiation of mouse hematopoietic progenitor cells in response to fibro- blastic and adipogenic cell contact.

J Michaeli, X Busquets. PV Escriba, D Colomer, V Richon, PA Marks, R Rifkind Membrane alterations associated with hexamethy- lene bisacetamide (HMBA) induced differentiation of murine erythroleukemia cells (MELC).

M Nakamura, A Tsunoda, K Sakoe, J Gu, A Nishi- kawa, N Taniguchi, M Saito Total metabolic flow of glycosph&olipid biosymhe- sis is regulated by activities of UDP-GlcNAc: lac- tosylceramide pi->3 N-acetylglucosaminyitransferase and CMP-NeuAc: lactosylceramide a%>3 sialyl- transferase in human hematopoietic cell line I-IL-60 during differentiation.

78. M Makishima, K Sampi, Y Honma, M Hozumi Effects of inhibitors of protein kinase activities on differentiation of human myeloid leukemia cells.

XI

79. G Tortora, S Pepe, G Baldassarre, C Bianco, YS Cho-Chung, AR Bianco, F Ciardiello Overexpression of protein kinase A subunits differ- ential’ ,I affects morphology, growth and diffel,entia- tion or human and rodent epithelial cells.

80. DT Yamanishi, JA Buckmeier, FL Meyskens JR Induction of tumor suppression/cell senescence in human melanoma cells following transfection of protein kinase C PII gene.

Sunday, September

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