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

30

the non-SCLC group, although not statisti-

cally significant, the percentages of both

IKT3+ and OKT4+ T-lymphocytes in the

peripheral blood lymphocytes (PBL) were

slightly decreased, associated with a slight

decrease in the OKT4+ to OKT8+ T-cell ratio.

In contrast, the PBL of the SCLC patients

showed significantly lower proliferative

responses to phytohemagglutinin and h,,ma,

recombinant interleukin 2 than did the PBL

of both the SCLC patients and the non-cancer

control group. The ability of PBL to produce

lymphokines (interleukin 2 and macrophage

activating factor) was significantly im-

paired in the SCLC group but not in the non-

SCLC group. These results suggest that sup-

pression of helper T-cell functions and/or

potentiation of suppressor T-cell functions

should occur in patients with SCLC.

Increased Circulating Activated T-cells in

Lung Cancer.

Tsuyuguchi, I.~ Shiratsuchi, H., Fukuoka, M.

Osaka Prefectural Habikino Hospital, Osaka

583, Japan. Chest 89: 705-708, 1986.

T-cell activation (Tac) antigens, which

are closely associated with the receptors

for interleukin 2 (IL 2) and expressed on

activated ~m~n T-lymphocytes, are found on

a small percentage of normal peripheral T-

cells. Elevated levels of Tac antigen-

positive (Tac +) cells were observed in a

high proportion of patients with untreated

primary lung cancer assessed by using

monoclonal anti-Tac antibody. The mean per-

centage of Tac + cells in peripheral blood

lymphocytes was 13.1 + or - 6.4 percent in

patients with primary lung cancer (n = 67),

as compared with 4.3 + or - 1.9 percent in

normal controls (n = 30) (p < 0.001). No

significant differences were observed among

the cell types of lung cancer examined

(adenocarcinoma and squamous and small cell

carcinoma). The stages of the disease also

showed no significant differences in the

development of Tac + cells. Our results sug-

gest that T-cell-mediated active inm~ne

mechanisms against malignant cancer cells

are operative in patients with lung cancer,

resulting in an increase in activated T-

cells in the peripheral blood, although it

remains to be elucidated whether these ac-

tivated T-cells exert a favorable or un-

favorable effect on their host.

Functional Characterization of T Lymphocytes

Propagated From ~,,an Lung Carcinomas.

Kurnick, J.T., Kradin, R.L., Blumberg, R. et

al. l~mlnopathology Unit, Department of

Pathology, Massachusetts General Hospital,

Boston, MA 02114, U.S.A. Clin. Immunol. Im-

munopathol. 38: 367-380, 1986.

Tissue fragments from biopsies of six

patients with malignant tumors of the lung

were cultured in interleukin 2 (IL-2). Cul-

tures of proliferating lymphocytes were iso-

lated from all cases. Tumor cell lines

(small cell carcinoma and adenocarcinoma)

were established in parallel cultures from

two of these patients. Lymphocytes that

proliferated in vitro were virtually all ma-

ture T lymphocytes (> 95% T 3+, TII+). The

T 8+ subset accounted for an average of 70%

while T 4+ cells averaged 20% of the cells in

culture. HNK-I antigen was presented on 23%

of cells. Seventy-four percent of cells

expressed la (HLA-DR) antigens. B cells did

not proliferate under these conditions. In

all cases the cells lysed K562 targets and

were active in lectin-mediated cytolysis

against human lymphoblasts. All cultures

produced lymphokines (IL-2 and IFN-gan,na)

when stimulated with PHA. Lymphocytes grown

from a tissue specimen with adenocarcinoma

were capable of killing autologous tumor

cells in vitro. Specific cytotoxicity has

been maintained by these cultured lym-

phocytes for greater than 6 months. IL-2 ac-

tivated peripheral blood cells in this case

showed little specific cytotoxicity for

autologous tumor cells. Lymphocytes from

another specimen of adenocarcinoma also

lysed this tu~or, but cells from the other

four specimens did not. Lymphocytes

propagated from the specimen of small cell

undifferentiated cancer did not lyse

autologous tumor cells. These data show that

primary lung tumors contain activated T

cells which will respond to IL-2 in vitro.

These tumor-infiltrating lymphocytes have

demonstrable function, which can include

cytolytic activity against autologous lung

tumor.

Biosynthesis of Procalcitonin in Small Cell

Carcinoma of the Lung.

Cate, C.C., Pettengill, O.S., Sorenson, G.D.

Department of Pathology, Dartmouth Medical

School, Hanover, NH 03756, U.S.A. Cancer

Res. 46: 812-818, 1986.

In~unoreactive calcitonin (CT) secreted

by DMS 53, a cell line derived from human

small cell carcinoma of the lung, consists

almost entirely of molecular species larger