Mount Sinai Medical Center, New York, NY

10029, U.S.A. Cancer Res. 46: 2600-2605,

1986.

Analyses of enzymes from various meta-

bolic pathways in pulmonary carcinoid tumors

and radiological measurements of their

volume increase were compared with those for

lung carcinomas of various cell types. The

results describe new biochemical features in

carcinoid tumors, present the first quan-

titative evidence for their slow growth rate

(i.e., long doubling time) in vivo, and show

that measurement of 2 or 3 appropriate en-

zymes in biopsy samples can guard against

instances in which carcinoids and adeno- or

oat cell carcinomas are mistaken for one

another on histological examination. The

uridine kinase to thymidine kinase ratio as

well as beta-galactosidase concentration of

carcinoid tumors were 5 times higher than of

carcinomas, and their gamma-glutamyl

transpeptidase was below that of all 35

adeno- and the ii squamous cell carcinomas.

Thymidine kinase, which bears a quantitative

inverse correlation to volume doubling time

(irrespective of cell type), had much lower

titers in the 9 carcinoids than in the 6 oat

cell carcinomas and reflects most clearly

their very different (despite common

histogenesis) clinical malignancy. Owing to

their long doubling time, carcinoid tumors

on the average required a much longer period

(40.5 years) to attain final volume than did

carcinomas (17.8 years). The calculated mean

age of the subjects when growth began, -0.5

years (as opposed to 51 years for

carcinomas), suggests a prenatal or early

childhood inception for pulmonary carcinoid

tumors.

Anchorage Dependency Effects on

Difluoromethylornithine Cytotoxicity in

H,m~, Lung Caxcinoma Cells.

Luk, G.D., Baylin, S.B. The Oncology Center,

The Johns Hopkins University School of

Medicine, Baltimore, MD 21205, U.S.A. Cancer

Re. 46: 1844-1848, 1986.

Difluoromethylornithine (DFMO), a

specific, irreversible, enzyme-activated in-

hibitor of ornithine decarboxylase activity,

the first and rate-limiting step in

polyamine biosynthesis, has been shown to

inhibit neoplastic cell proliferation in

culture. In most cases, such inhibition is

not accompanied by cell loss, with the ex-

ception of multiple cell lines of human

small lung carcinoma (SCC), a human leukemia

29

cell line (HL-60), and possibly the BI6

melanoma cell line. The first two cell types

grow as anchorage-independent suspension

cultures, the HL-60 as single cells and the

SCC as multicellular spheroid aggregates.

Moreover, in the spectrum of ~man lung car-

cinoma cells in culture, the SCC cells

respond in a cytotoxic manner to DFMO,

whereas the non-small cell lung carcinoma

(non-SCC) cells, which are anchorage depen-

dent, show only growth inhibition, without

actual cell loss. In the present study, we

have investigated relationships between

anchorage-dependent and -independent growth

patterns of cells in culture and their

response to DFMO treatment. Two non-SCC lung

cancer cell lines, which normally grow as

anchorage-dependent monolayers, show growth

inhibition hut no cell loss with the addi-

tion of DFMO. When these anchorage-dependent

cells were forced to grow as multicellular

aggregates, by coating the culture flask

with Teflon, the cells developed an in-

creased sensitivity to DFMO. They showed not

only inhibition of cell proliferation but

also cell death. Two SCC cell lines, which

normally grow as anchorage-independent

spheroids, developed adherence to the cul-

ture dishes coated with fibronectin. These

cells, which show a cytotoxic response to

DFMO during normal anchorage-independent

growth, developed a decreased sensitivity to

DFMO, showing only cell growth inhibition,

but no cell death when treated during

anchorage-dependent growth. Our data thus

suggest that the state of anchorage depen-

dence of lung cancer cells in culture is a

critical factor in determining their

response to polyamine depletion during

treatment with DFMO.

Inm~noregulatory T-Lymphocyte Functions in

Patients With Small Cell Lung Cancer.

Masuno, T., Ikeda, T., Yokota, S. et al.

Third Department of Internal Medicine, Osaka

University Medical School, Fukushima-ku,

Osaka 553, Japan. Cancer Res. 46: 4195-4199,

1986.

The present study was performed to

elucidate the differences in immune status

between patients with small cell lung cancer

(SCLC) and those with non-small cell lung

cancer. The study group consisted of 18

patients with SCLC and 15 with non-SCLC. Two

healthy volunteers and 13 patients with

benign disease were also included in the

present study as the non-cancer control. In