Advances and challenges in cancer research

110

Radiation

Oncology,

WEDNESDAY,

OCTOBER

CYTOKINE

IN CONGENITAL,

Malcolm James

NETWORKS

Biology,

Physics

October

1989, Volume

17, Supplement

1

4, 1989 IDIOPATHIC

AND IATROGENIC

NEUTROPENIA

A.S. Moore

Ewing Laboratory

of Uevelopmental

Hematopoiesis,

Memorial

Sloan-Kettering

Cancer

Center,

New York, USA

Additive and synergistic interactions between hemopoietic growth factors and cytokines (Interleukins and colony stimulating factors) can be demonstrated in vitro in clonogenic and suspension cultures of murine and (5human bone Inarrow. Purification of early stem cells by combinations of purging .~ith.cytotoxic-agents fluorouracil, 4-HP cyclophosphamide) and selection with monoclonal antibodies for CD34+, CD33- cells permits analysis of factor interactions at the level of the primitive pluripotential stem cell. Interactions between IL-l, IL-6, TNF, G-, GM- and M-CSF, and IL-3 can be monitored. In vivo, IL-l alone, or in combination with G-CSF, produces accelerated reconstitution of hemopoiesis after chemotherapy, irradiation and bone marrow transplantation in murine and primate systems. IL-1 is directly radioprotective in vitro on populations of human hematopoietic stem cells. In addition IL-1 elicits cytokine cascades that may have positive or negative actions on lymphohemopoiesis. Induction of oroaucts of th cyclooxygenase and lipoxygenase pathways, as well as tumor necrosis factor and TGF-beta, modulate hemopoiesis. Recent clinical trials usinq G-CSF in patients with idiopathic or congenital disorders have demonstrated increases in peripheral blood neutrophil counts. The etiology of these disorders remains obscure but we have analvzed the structure of the G-CSF qene bv Southern blottinq. as well as the inducibilitv of G-CSF mRNA and bioactive G-CSF in bone marrow fibroblasts: -Trans-modulation.of growth factor and cytokine receptors on neutrophils, monocytes, and possibly early progenitors are also involved in these complex regulatory interactions.

WEDNESDAY,

OCTOBER

4, 1989

SamuelBroder,M.D. Director,NationalCancerInstitute,National Institutes of Health, Bethesda, Maryland and a brief sumary of major challenges will be including~dioth~pyand activeinthenweltrea~tresearh, newccmbinationtherapieswhichincluderadiotherapy.l'hesenewthrapiesrestona solidbase of achievementsincancerm5mrchwhich include: 1) An extensionof the scienceof cancerpreventionand of early detection.2) An urxkrsta&irqof the molecularbasis for cancer,includingthe identification 3) The characterization of large broadfamiliesofgenesthataccelerateor~~therrralignantstate. numbersofphysiolcgicgrmth factorsandtheirreceptors,whichwknp msentatthewroqtimeandinthe of new familiesof pathogenic wrong place bring about neoplastictransformation.4) The elucidation of variousbiochemicalstrateyiesused by cancercells to evade retrwimses. 5) The identification cytotoxictherapy. 6) The elucidationof cells,which can cause tumor regressionunder conditionsof adoptivetherapy. 7) The initiationof nwel regimensinv01vi.qgeneticallyengineeredproductsto treat of practicaland effectivetherapyfor severaltmors patientswithadvancedcancer. 8) The formulation when they are in an early stage,i.e. in an adjuvantsetting. 9) Theuse ofnwelmlti-modality therapy forcertainadvancedcancers. 10) The develmt of mpemmputermodeling fordmgdesign. Anwerviewoftheachiev~~incancerresearch presented. The NC1 has been extremely

The challengeswe face includeextemionofnewtechmlcgyto all segments of our societyincludirq of cancermortal.ity inminoritygroups andthe people currentlysufferingdispropcrtionaterates

Edically

LlndWserved.