Derivatives of benzo(c)fluorene. XVI. Absorption, distribution and elimination of 3H-benflurone, 5-(2-N,N-dimethylamino)ethoxy)-7-oxo-7H-benzo(c)fluorene hydrochloride in rats after oral and intravenous administration.

3H-benfluorone administered orally to rats, persists for a long time in the stomach; it is absorbed only partly and eliminated mostly through the feces (about 80% within 7 days). The maximum levels in the blood and the organs were determined in the 1st and 9th hour after application. Benflurone penetrates through the placentary barrier. Within one week 13% of the administered radioactivity was eliminated through the urine and 8% through the bile within 12 h. It has been demonstrated that benflurone was excreted through the milk, as well. After being administered intravenously, benflurone moves quickly from the blood into the tissues. The high levels were recorded in the heart, the lungs, the kidneys, the brain and the liver. After intravenous application about 70% of the administered radioactivity was eliminated within one week through the feces and about 24% through the urine, almost 54% through the bile within 12 h.

Comparison of the effectivity of two diaminocyclohexane Pt-complexes.

A group of Pt-complexes was tested in various in vitro and in vivo systems. Murine P388 leukemia for the in vivo testing and three sublines of L1210 leukemia for the in vitro testing of two 1,2-diaminocyclohexane (DACH) derivatives of platinum were used. The effectivity of DACH-Pt(II) citrate and DACH-Pt(II) isocitrate with different ratio of trans- and/or cis-DACH was compared on the sensitive strain of L1210 and two resistant sublines: L1210 resistant to cis-diammine-dichloroplatinum(II) (cis-DDP) and L1210 resistant to trans-DACH-Pt(II) citrate. No cross-resistance was found between the DACH derivatives and cis-DDP. Slightly higher activity of citrate and trans-DACH in comparison with isocitrate and cis-DACH was found both in suspension culture and in vivo testing.

3H-arginine-rich cationic proteins in cytosol of fibrosarcoma, induced by methylcholanthrene in rats.

With the use of 3H-arginine it is shown that among soluble cytosol of fibrosarcoma, induced by 20-methylcholanthrene in rats there appear cationic proteins rich in arginine with content of amino acid of about 10%. The amount of these proteins in cytosol fraction is higher than in cytosol of another types of experimental tumors. The role of arginine-rich cationic proteins in cytosol fraction is briefly discussed.

Distribution of 64copper in the blood and different tissues of mice bearing induced fibrosarcoma.

To understand the nature of copper distribution during malignancy, 27 strains A/RB mice with fibrosarcoma were used. Tracer methodology with radioactive isotope of copper (64Cu) was applied. In the study made at different time intervals after isotope administration whole blood plasma and different tissues like liver, heart, spleen kidney and brain were investigated. Liver nuclear fractions were also examined. Distribution of 64Cu in different tissues reflected interesting results. While the incorporation pattern in the liver showed gradual fall from 8 h of isotope administration, the tumor tissue exhibited gradual elevation, compared to the controls. The effect of this finding is discussed.

Changes in tissue and serum activity of cathepsin B-like cysteine proteinase during colorectal carcinogenesis by 1,2-dimethylhydrazine in mice.

The activity of cathepsin B-like cysteine proteinase in the mice colon was studied during carcinogenesis induced by 1,2-dimethylhydrazine dihydrochloride (DMH). Before starting the treatment with DMH, the activity of the observed enzyme was very low in the colorectal area but the activity in the serum was rather high. In the course of carcinogenesis, the local activity markedly increased in the stroma equally as in the cells of developing tumors while the serum activity slightly decreased. Following the total ovariectomy, no significant changes in the local activity or in the serum activity were found. Possible causes of these variations are discussed.

Metabolic characterization of three hamster melanoma variants.

Some enzyme activities and metabolic features of the black Ma melanotic, brown MI melanotic and Ab amelanotic melanomas of hamster were investigated. The activities of hexokinase and phosphofructokinase were similar in all three melanomas, the activity of NAD-dependent glycerol-3-phosphate dehydrogenase was higher in the amelanotic melanoma and that of pyruvate kinase and lactate dehydrogenase were slightly lower in MI than in the other tumors. The activities of citrate synthase, succinate dehydrogenase and malate dehydrogenase were higher in the Ma and MI melanotic melanomas than in the Ab amelanotic melanoma. The rate of labeled CO2 production from 6-14C-glucose, 1,5-14C-citric acid and U-14C-glutamine was about 2 times higher in melanotic melanomas than in amelanotic one, while no significant differences among the three melanomas were found in respect to 1-14C-glucose and U-14C-glycerol-3-phosphate. The production of 14CO2 was much higher from 1-14C-glucose than from 6-14C-glucose in all the melanomas studied. L-DOPA stimulated the production of 14CO2 from 1-14C-glucose much stronger in the Ma and MI melanomas than in the Ab melanoma. In none of the tumors the incorporation from 6-14C-glucose to CO2 was affected by L-DOPA. It is postulated that oxidation of glucose via the pentose phosphate cycle is involved in melanogenesis.

Serum lysozyme activity in patients with lung carcinoma subjected to radiotherapy.

Lysozyme activity was determined in undiluted and diluted sera of 30 patients with lung carcinoma and of 40 healthy individuals. Blood was collected before radiotherapy, in half of its course, just after completion of radiotherapy, and three weeks and three months later. In the controls the same time spacing was kept. Lysozyme was found to be increased both in undiluted and diluted sera. Enhancement of the lysozyme activity may be due to the presence of immune complexes (antigen--antibody) which are probably responsible for the release of the enzyme from the viable neutrophils. High activity in diluted sera indicates an increase of lysozyme inhibitors in sera of cancer patients. Radiotherapy has not induced significant changes in the enzyme, either during its course of after its completion as confirmed by three-month observation. Taking into consideration the role of the lysozyme in anticancer mechanisms it appears that determination of its activity may be of value in the course of cancer disease.

Studies on the distribution of the antigens detected by some newly prepared monoclonal antibodies in normal hemopoietic and leukemic cells.

A great number of hybridoma clones has been developed in two independent fusions after immunization with cells of a human non-T, non-B REH leukemic cell line, recognizing different differentiation antigens on leukocytes. Only four of these new murine monoclonal hybridoma-derived antibodies (Bra20, Bra30, BraFB6 and BraEA10) have been used in our study for determination of their reactivity spectrum in normal blood cells and fresh lymphoid and non-lymphoid leukemic cells. The resulting reactivity spectra of these four monoclonal antibodies in normal hemopoietic and leukemic cells in indirect immunofluorescence assay are in agreement with supposed Ia-like reactivity for Bra20, Bra30 and Bra FB6 monoclonal antibodies and "common" leukocyte specificity for BraEA10 monoclonal antibody.

Interaction of cis-diamminedichloroplatinum (II) with mitochondrial phosphate carrier.

Effect of cis-Pt(II) on mitochondrial phosphate transport has been studied. The inhibition of transport by cis-Pt(II) is demonstrated by the effect of the drug on mitochondrial phosphate-induced swelling and respiration. A diminished 14C-NEM binding to 33 kD mitochondrial protein in the presence of cis-Pt(II) suggests that cis-Pt(II) inhibits mitochondrial phosphate transport by a direct interaction with mitochondrial phosphate carrier.

Stimulation of differentiation in human melanoma cells by dimethyl sulphoxide (DMSO).

Stimulation of differentiation in human amelanotic melanoma cell line by 0.5, 1, 1.5 and 2% DMSO expressed in increased melanization was linked to significant decrease in proliferation rate of these cells. After removing DMSO the 0.5 and 1% samples became within 14 days again amelanotic with the same growth capacity as untreated controls. The 1.5 and 2% samples did not recover after DMSO removing and the inhibition of proliferation was irreversible.

The physico-chemical properties of tumor cells with different metastatic potential.

Authors investigated the total and surface sialic-acid content and elpho mobility of Lewis lung lines with low (LLT-parent) and high (LLT-HH selected) metastatic capacity. They pointed out, that the total and surface sialic-acid content of LLT-HH primary tumor cells is higher than in the cells of the LLT line. Despite the increase of sialic-acid on the cell surface, the electrophoretic mobility of the cells was unchangeable. The changes in sialic acid content are the markers of the metastasizing cells, but not of the highly metastatic cell lines.

Quantitative structure-activity relationship (QSAR) applications in chemical carcinogenesis. III. QSAR analysis of some phenolic antioxidants.

Quantitative structure-activity relationships (QSAR) were formulated for a series of 22 phenolic inhibitors of carcinogenesis, taking into account: a) the inhibition of forestomach tumor induction in benzo(a)pyrene fed mice, as biological parameter and b) minimal topological differences (MTD), lipophilicities, quantum mechanic indices (epsilon LE, epsilon HO, and delta E1) and Hammett constants, as structural and physicochemical ones. Significant multilinear regression equations were found for a set of 22 compounds, two 2,6-di-tert-butyl derivatives (4 and 22) diverting from the general correlations. The obtained correlations support the conclusion that the antioxidizing potential is not directly responsible (in a rate determining step) for the inhibitory properties of the investigated phenols.

Acceleration of neoplasms of reticular tissue with syngeneic thymic graft under renal capsule and gamma radiation.

Weanling ICRC female mice were given syngeneic neonatal thymus graft under renal capsule and two weeks later whole-body gamma-radiation (group ITR). The findings on ITR were compared with three controls--untreated (C), thymus grafted (IT) and irradiated (IR). In ITR group 15/15 developed generalized neoplasms of reticular tissue at 5 to 8 months and single mammary tumor at 7 months. In IR group 12/13, 21/25 in IT and 5/23 in C had neoplastic changes at 7-month onwards. Microscopically these neoplasms had diffuse or focal proliferation of modified reticulum cells, histiocytes, lymphocytes and giant cells. Localized thymic tumors showed either the same picture or prominence of small lymphocytes. Mammary tumors developed in 12/25 IT, and 8/25 in C and nil in IR.

An original method for isoantiperistaltic jejunogastroplastic operation without intestinal inserts in distal subtotal resection of the stomach.

A novel method for subtotal gastric resection is described with the construction of an isoantiperistaltic artificial stomach formed from the small intestine and the duodenum at Treitz's ligament without any intestinal inserts, Brown's and Roux's anastomoses, and with an invaginated anastomosis between the stomach and the reservoir measuring 1.5-2 cm in length. Fifty-nine operations were performed. No incoherent sutures were observed in the gastric-reservoir anastomosis. In 1 patient, due to a technical fault, duodenal necrosis with fatal outcome was encountered. Two patients developed pancreatic necrosis of the horizontal part of the duodenum. The general condition of all of the followed-up patients is good. They had a weight gain ranging from 2 to 15 kg. When a broad anastomosis (exceeding 3 cm) was constructed, in 6 patients examined by endoscopy done in a horizontal position, small volumes of bile reflux into the gastric stub were found. In gastric resections performed according to Billroth II, a refluent gastritis was observed in 62.3% of the patients.

Non-Hodgkin's lymphomas of Waldeyer's ring.

The following data have been achieved in investigation of 40 patients with non-Hodgkin's lymphoma involvement of the Waldeyer's ring (WR): a) Palatinal tonsils and nasopharynx are the parts of WR most frequently involved. b) Involvement of WR warrants a careful X-ray, and/or endoscopic examination of the gastrointestinal tract. c) WR is most frequently involved in patients with diffuse histiocytic and lymphohistiocytic NHL. d) The basic treatment in patients of clinical Stage I and II is local-regional radiotherapy, in those of Stage III and IV, it is combined chemotherapy. Of key importance in the choice of the strategy and tactics of treatment is the determination of histological subgroup. e) Prognosis in patients with NHL probably does not depend on the origin of the disease but rather on basic stratification criteria (clinical stage, histological subgroup, occurrence or absence of systemic symptoms, presence or absence of bulky tumors). The results are significantly influenced by the degree of radicality of treatment. Methods of a "local-regional" treatment appear to be inadequate in the majority of patients with NHL of high and intermediate grade malignancy. Consequently, the involvement of WR does not seem to represent a distinct clinical-pathological entity.

Problems with prognostic criteria in patients with chronic lymphocytic leukemia with special reference to DPP II assessment.

106 consecutive patients with chronic lymphocytic leukemia (CLL) were entered into prospective study with the aims of finding out whether a detailed clinical, biochemical, immunological and cytochemical examination might help to subclassify CLL with respect to prognosis. None of the biochemical and immunological parameters studied correlated either with the clinical stage of the disease according to Rai, or with further evolution of the disease. On the other hand, the results of cytochemical tests indicated that the reaction for DPP II (dipeptidylaminopeptidase) might be of prognostic value, because in patients with stable disease, significantly lower number of DPP II positive lymphocytes were found when compared with patients suffering from progressive disease. The authors also point out some short-comings of Rai's staging system in respect to its prognostic significance.

Pleiomorphous histiocytic sarcoma arising in a patient with histiocytosis X.

An adult woman was followed up for the occurrence of multiple successive cutaneous and mucosal tumors of small size and classical histiocytosis X structure (histiocytoeosinophilic granuloma). In the second phase of the patient's clinical history there were successively appearing nodular or infiltrative cutaneous and subcutaneous tumors histologically resembling polymorphocellular sarcoma close either to malignant lymphogranuloma or to recently described "regressing atypical histiocytosis". Despite the marked cellular atypia and polymorphism the tumors exhibited a relatively favorable clinical course. Beside clearly sarcomatous structures, some of them displayed also transitional structures to histiocytosis X. Immunohistologically the atypical cells showed features of both the Langerhans' line and non-specific histiocytes. Ia-like antigen was positive in most of the elements. Quite occasional cells contained detectable amount of S-100 protein. Electronmicroscopy revealed quite sporadic structures resembling Langerhans granules.

Mechanism of action of 1-beta-D-arabinofuranosyl-5-azacytosine and its effects in L1210 mouse leukemia cells.

Ara-5AC depresses the growth of L1210 cells in vivo in a manner that is schedule-independent and at the dose levels which are similar to those of ara-C. The 50% inhibitory concentration for ara-5AC in L1210 system is about 0.75 microM. In distinction to ara-C the drug does not elicit the proliferation of proerythroblasts in the mouse bone marrow. It is phosphorylated by dCyd kinase, and the respective Km value is 70 microM. Ara-5AC is incorporated into DNA and almost completely blocks the incorporation of thymidine at a concentration of 10 microM.

Haptoglobin and proteinase inhibitors in the blood serum of women with inflammatory, benign and neoplastic lesions of the ovary.

Blood sera of women with myomas of the uterus, benign or malignant neoplasms of the ovary and with inflammatory conditions were examined by determining the haptoglobin concentration and functional activities of: alpha 2-macroglobulin, alpha 1-proteinase inhibitor and alpha-cysteine proteinase inhibitor. In the women with ovarian cancer, as compared with the control group, a significant increase of haptoglobin, alpha 1-proteinase inhibitor and alpha-cysteine proteinase inhibitor was found (p less than 0.001). On the contrary bioactivity of alpha 2-macroglobulin was depressed (p = 0.01). The observed increase of alpha-cysteine proteinase inhibitor activity in the groups with ovarian tumors and ovarian cysts was not related to the inflammatory state as estimated by the haptoglobin concentration.

Cytotoxic and mutagenic in vitro effect of 7-O-epoxyalkyl derivatives of daunomycinone. Part IX.

The cytotoxic effect of (7S)- and (7R)-O-epoxyalkyl derivatives of daunomycinone on leukemia P388 cells was followed in in vitro tests and their mutagenicity was determined by means of the bacterial SOS chromotest. The biological effects of the substances were compared with those of daunomycin, carminomycin and nogalamycin. The most efficient derivative proved to be the (7S)-9-acetyl-4-methoxy 7-O-(2,3-epoxypropyl)-7,8,9,10-tetrahydro-6,9,11-trihydroxy-5, 12-naphthacenequinone 10 which inhibited the DNA and RNA synthesis and proliferation of P388 cells on the level of daunomycin or carminomycin. The cytotoxic and mutagenic action of 7-O-epoxyalkyl derivatives of daunomycinone was affected by the length of alkyl and its configuration.

Retrovirus-like particles produced by human embryonal cells and cell lines derived from human malignancies.

Very small amounts of retrovirus-like particles were obtained from tissue culture fluids of various human cell lines. The particles were found in almost all cultures of rapidly growing human cells (embryo fibroblasts, various types of leukemias, melanoma, urinary bladder, lung and mammary carcinomas). Morphology and some biochemical characteristics of purified samples of these particles are presented. The particles resemble C-type mammalian retroviruses.

Hyperthermia inhibition of tumor cells growth in the presence of ruthenium red.

Ruthenium red (RR) is taken up by DS sarcoma cells as a linear function of its concentration. Higher temperatures produce a higher uptake. This increased uptake is coincident with an augmentation of Trypan blue inclusion. A diminution of calcium transport in the presence of RR is observed at hyperthermia, and its uptake is not linear but presents a plateau for all temperatures and concentrations. RR-cell membrane interaction seems to produce two different effects: an early blocking of calcium transport, and a later change of the physicochemical characteristics of the plasma membrane. On the colony forming ability of CA1 cell RR shows clearly an intrinsic toxic effect, and when present during hyperthermia a low but significant enhancement of tumor cells mortality.

Endocrine factors in the etiology of endometrial carcinoma.

In the blood of 39 women with endometrial carcinoma the FSH, LH, estrone, androstendion, estradiol and dehydroepiandrosterone were determined by the RIA method. Compared to the control group the estrone (303.3 +/- 44.3 pmol/l), estradiol (165.2 +/- 29.4 pmol/l) and the androstendion (5.24 +/- 0.44 nmol/l) were significantly higher. The source of the increased estrogen levels was mainly of adrenal origin. The peripheral conversion, i.e. aromatization of androstendion into estrone was particularly marked in the case of adipose patients. The unbalanced estrogen effect in the absence of progesterone is one of the decisive factors in the etiology of endometrial carcinoma.

Flow cytometry in brain tumors. I. Ploidy abnormalities.

Flow cytometry (FCM) was introduced for estimation of DNA content in 75 brain tumors. Among these astrocytomas (38 cases) and meningiomas (16 cases) predominated. Astrocytomas were histologically subdivided into 3 groups of malignancy grade. Aneuploid cell populations were found in 1 out of 4 cases of astrocytoma grade I, in 11 out of 20 astrocytomas grade II and in 10 out of 14 astrocytomas grade III of malignancy. DNA index (DI) in most aneuploid astrocytomas is in the range between 1 and 2. More than one cell population with aneuploid value of DNA was found in 36% of all aneuploid tumors.

Properties of Na+/K+ ATPase and alkaline phosphatase alter during spontaneous and radiation-induced leukemogenesis in mice.

We characterized properties of Na+/K+ ATPase and alkaline phosphatase in thymocytes or thymoblasts from mice of two strains: AKR, in which thymoma developed spontaneously and C57Bl, in which the development was induced by X-irradiation (total dose: 5.4 Gy in 3 fractions). We found that before thymoma could be discerned morphologically--properties of the two enzymes altered. There was a decrease in 86Rb uptake and in the rate of ATP hydrolysis per cell (both strains) as well as an increase in alkaline phosphatase activity per cell (C57Bl mice). In both spontaneous and radiation-induced thymomas 86Rb uptake, ATP hydrolysis and 3H-ouabain binding per cell were higher than in normal thymuses. Likewise, alkaline phosphatase activity per cell was higher in thymomas than in thymuses; this increase was accompanied by the appearance of additional isoenzyme(s) (1 in AKR, 2 in C57Bl). These changes were compared with cAMP content and 3H-thymidine incorporation, taken as indicators of the proliferative activity, and their high correlation in both AKR and C57Bl mice allowed to distinguish a pre-leukemic period. In that period thymoblasts clearly differed from the normal ones in Na+/K+ ATPase and alkaline phosphatase properties, as well as proliferation, although the morphology of the thymus was still unchanged.

Tumor growth enhancement and systemic responses of Ehrlich ascites carcinoma following intermittent whole body hyperthermia.

Intermittent whole body hyperthermia 42 degrees C (WBH(I) administered for 30 min daily during 7 days caused significant enhancement of the growth of Ehrlich ascites carcinoma. The tumoricidal effects of hyperthermia were evident from the cytological picture as well as from the increased activity of lysosomal enzyme of the tumor cells. Elevated plasma corticosteroid levels, adrenal hypertrophy, thymus involution and lymphocytopenia were observed in both normal and tumor bearing mice exposed to hyperthermia. The alterations were more marked in the tumor bearing groups. Withdrawal of treatment caused gradual restoration of stress effects. It appears that the tumoricidal effects of WBH(I) were counteracted and surpassed by the growth stimulatory effects induced probably by hormone mediated immunosuppression.

Postnatal carcinogenic study of 1,2-dimethylhydrazine dihydrochloride in rats.

The outbred SPF rats of the Ripb: Wist stock were applied subcutaneously 1,2-dimethylhydrazine dihydrochloride (DMHD) at a concentration of 0.036% and 0.144% from the first day of age after the birth. In nine experimental groups DMHD was administered for first 5, 10, 15 and 20 days of age after the birth at total doses of 0.36 to 2.16 mg. With the highest applied dose, all animals died during the treatment, further deaths were recorded in groups in which DMHD was administered for first 5 to 10 days. The maximum length of survival was one year. The conclusion of the study was achieved only by the control animals and by 36.6% of males and 13.8% of females of the experimental group. From the 24th week of age, hepatic and renal tumors were detected in rats. In the liver hepatocellular carcinomas and benign hepatomas occurred, and were found in all groups which had been applied DMHD, furthermore cholangiomas, mostly in the groups which had been applied DMHD up to the age of 15 days and cavernomas in the groups which had been applied DMHD up to the age of 20 days. Practically in all rats which had been administered DMHD focal preneoplastic hyperplasia of liver cells was detected. In the kidney always a mixed malignant mesenchymal tumor was found in all animals of the groups treated up to age of 15 days.

Relationships of steroid hormone receptors, age and histological characteristics in human breast cancer.

A number of 178 human primary mammary carcinomas were evaluated for estradiol receptor (ER) content, patients' age, histologic type, tumor histological grade of differentiation and content of elastosis. For a subset of 78 cases progesterone receptor (PR) was also assayed. ER positivity was significantly elevated in patients over 50 years while PR positivity rate was increased in patients under 50; ER-positive-PR-positive (ER + PR +) cases were evenly distributed among age groups. Correlations of ER and PR with histological features revealed that: a) high levels of ER were found in lobular, cribriform and colloid carcinomas; b) ER+ cases but not PR+ tumors were more frequent in well differentiated tumors; c) ER+, PR+ and ER+ +PR+ tumors were strongly related to the presence of elastosis; d) contrasting with ER-PR+ tumors, ER+ PR+ cases were associated with features indicative of a favorable prognosis. It is concluded that the determination of ER and PR in mammary malignant tumors brings information regarding the evolution of breast cancer in human patients and the biology of malignant mammary cells.

Electron microscopy in assessment of the biological behavior of human papillomavirus infections in the uterine cervix.

To asses the natural history of human papillomavirus (HPV) infections in uterine cervix, currently implicated in etiology of cervical cancer, a prospective follow-up study has been conducted for 418 women at our clinic since 1981. The present communication summarized the current follow-up data of these patients, with special emphasis on detection of the virus in cervical punch biopsies, as correlated with other characteristics pertinent to the clinical behavior of cervical HPV infections. On each attendance, the patients are subjected to colposcopy accompanied either by Papanicolaou (PAP) smears or punch biopsies. The latter are analyzed for the cytopathic changes of HPV, for concomitant cervical intraepithelial neoplasia (CIN), for HPV structural proteins with IP-PAP technique as well as on transmission electron microscopy (TEM) for the presence of HPV particles. The local immunocompetent cell (ICC) infiltrates are analyzed using ANAE technique to define B cells, MPS cells and T cells and monoclonal antibodies (McAb) for T cell subsets, NK (natural killer) cells and Langerhans cells. HPV particles were disclosed with equal frequency (approx. 65%) in all three types of HPV lesions. Surprisingly, HPV particles were present in 70% of the biopsies derived from the regressed lesions (e. g. in those without histological evidence of HPV lesions), suggesting a possibility of a latent HPV infection. Presence of viral particles did not bear any direct correlations with the expression of HPV antigens, intensity or cellular composition of the ICC infiltrate, defined by ANAE or using McAb. Presence of HPV particles was not a major prognostic determinant, whereas the clinical course was most significantly influenced by the grade of HPV-associated CIN, to which regression was inversely and progression directly related. The results clearly confirm that cervical HPV infections are capable of progressing into carcinoma in situ and thus present with a natural history equivalent to that of classical CIN.

Immunological reactivity in children with Wilms' tumor.

Cellular immune reactivity was investigated in 49 newly diagnosed children with Wilms' tumor and compared to age-matched control. The level of total T (T4 degrees) and B lymphocytes was normal while the relative number of T lymphocytes with high affinity receptors for sheep erythrocytes (T29 degrees) was significantly decreased in the patients studied. The lymphocyte response to PHA in vitro was diminished but PHA-induced lymphokine production was not altered. The depression of T29 degrees level and lymphocyte reactivity to PHA was associated with high grade tumor rather than with the clinical stage. Lymphocytes of 42-47% patients reacted with autochthonous and allogeneic KCl tumor extracts in the migration inhibition test and the degree of reactivity was related to the histological differentiation of the tumor.