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Prostaglandin E2 Production by Human Tumors. Defense Mechanism Against the Host? A Preliminary Report
197 the response of orated material that nonnal human blood lymphocytes to the T cell phytohemagglutinin and concanavalin A as well as the mixed lymphocyte reaction. Thus, it appears that there is selective inhibition of different lymphocyte functions material elaborated from different neoplasms. W. J. C. 3 figures, 2 tables, 34 references
P:rnstaglandin E2 Production by Human Tumors. Defem,e Mechanism Against the Host? A Preliminary Report
A.
ATTALLAH, J. B. LEE, J. L. AMBRUS, C. M. AMBRUS, C. KARAKOUSIS AND H. TAKITA, Roswell Park Memorial Insti-
tute and The State University of New York at Buffalo, Departments of Medicine, Pediatrics, Surgery and ObstetricsGynecology, Buffalo, New York Res. Comm. Chem. Path. Pharm., 43: 195-201 (Feb.) 1984 Recent studies have suggested that prostaglandins may have an important role in cellular proliferation and differentiation. The purpose of this investigation was to compare prostaglandin E2 concentration in surgically removed human malignant tumors and adjacent nonmalignant tissues. Healthy and tumor tissues from the same organ were obtained from 11 patients with malignant tumors. Of these specimens 7 were malignant melanomas, 3 sarcomas and 1 adenocarcinomao Tissue prostaglandin E2 content was higher in malignant compared to normal which also was true when paired differences were analyzed. These findings support the view that prostaglandins may have a role in cell proliferation and/or vascular supply to tumor tissues. The hypothesis also was discussed that prostaglandin E2 may represent a tumor against host defense, since it can decrease spontaneous and antibody-dependent cytotoxProstaglandin E2 also may have a role in tumor-induced osteoporosis and hypercalcemia. If this hypothesis is correct prostaglandin E2 synthesis inhibitors may be used as auxiliary antitumor agents. P. M. H. 2 30 references
A Small Molecular Weight Growth. Inhibitory Factor in Tissue Cultm·e Supernatants
L J.
Catholic Medical
14: 415-432, 1983
substances of cellular origin have been as chalones or as acid inhibitors. Most of the latter substances were found in supernatants of established normal human cell lines. This is based on the common observation that growth of mammalian cells in tissue cultures decreases and eventually stops as the concentration of cells increases. Optimal growth usually occurs between the low and high cell concentrations. Bacterial growth often follows the same pattern. This phenomenon commonly is attributed to contact inhibition owing to the increased proximity of the cells in concentrated cultures. The author considers the hypothesis that decreased growth may be owing to synthesis of a growth-retarding material by the cells themselves or the gradual accumulation in the medium of a growth-retarding agent, normally produced and released by the cells but effective only when reaching a critical concentration in the surrounding extracellular milieu. The author found a small molecule in tissue culture supernatants
with UHH,,,v,n effects on the parent and other cells. Supernatants from stationary phase cultures of a human normai cell line inhibited the of the parent cells even when the latter were in optimal concentrations. Inhibitory activity was associated with small molecular weight fractions prepared by filtration. Fractions with materials <5,000 daltons were the most active. Growth inhibition also was observed with fractions <1,000 daltons. Similar growth inhibition of parent cells was observed with the small molecular weight fractions of supernatants from the human acute lymphoblastic leukemia cell line CCRF-SB, the human lung cancer cell line A-549 and a mouse leukemia SL-1210 line. The study demonstrates that supernatants from tissue cultures with high cell concentrations failed to support the growth of the parent cells even when the latter are diluted to optimal concentrations. This result cannot be explained by crowding alone nor by a lack of nutrients in the medium used. Complete inhibition of growth with the most active fractions was associated with death of most cells in the test culture. Usually, the cells were viable at 24 hours but showed progressively larger numbers of trypan blue permeable cells on subsequent days. Mild inhibition was not associated with extensive cell death and the cultures eventually caught up with the controls. Differentiation of growth inhibition from cytotoxicity can be extremely difficulto P M. H. 6 tables, 17 references Antitu.mor Studies of 2-Amim::i-2-Thiazoi.i.ne and Other Tumor-Modifying Agents
J. PINE, E. A. MIRAND, Jo L. AMBRUS AND F. G. BOCK, Departments of Experimental Therapeutics, Biological Resources and Pathophysiology, and Orchard Park Laboratories, Roswell Park Memorial Institute, Buffalo, New York
M.
Jo Med., 14: 433-449, 1983 Recently, interest has developed in the use of biological modifiers of tumors as antitumor agents. Puck originally proposed the concept of reverse transformation of transformed cells via restoration of normal membrane and organelle structure. The re-establishment of high intracellular levels of cyclic adenosine 3',-5'-monophosphate was considered paradogmatic of this effect. The authors examined 2-amino-2-thiazoline and as antitumor agents in several rodent tumor systems. 2-Amino-2-thiazoline administration reduced tumor incidence in outbred ICR Swiss female mice and doubled the survival of leuRA233 and diean.cuoui; host or tumor prostaglandin levels, platelet aggregation and host immunity, respectively, ranged from marginally effective to ineffective against Friend virus infection. However, 2-amino-2-thiazoline was ineffective against 4 other induced and transplanted mouse tumors, and did not increase differentiation or decrease transformation notably in any of several tumor cell systems. No in vitro or in vivo tumor system was found to be more than marginally affected by l-thiazolidine-4-carboxylate. Thus, 2amino-2-thiazoline alone had significant antitumor activity in inhibiting late stages of viral-induced or carcinogen-induced tumor progression but could not be demonstrated as an agent of reverse transformation. 2-Amino-2-thiazoline has been of commercial use as a photographic developer and may function as a biological antioxidant. However, it is unlikely that this
P:rnstaglandin E2 Production by Human Tumors. Defem,e Mechanism Against the Host? A Preliminary Report
A.
ATTALLAH, J. B. LEE, J. L. AMBRUS, C. M. AMBRUS, C. KARAKOUSIS AND H. TAKITA, Roswell Park Memorial Insti-
tute and The State University of New York at Buffalo, Departments of Medicine, Pediatrics, Surgery and ObstetricsGynecology, Buffalo, New York Res. Comm. Chem. Path. Pharm., 43: 195-201 (Feb.) 1984 Recent studies have suggested that prostaglandins may have an important role in cellular proliferation and differentiation. The purpose of this investigation was to compare prostaglandin E2 concentration in surgically removed human malignant tumors and adjacent nonmalignant tissues. Healthy and tumor tissues from the same organ were obtained from 11 patients with malignant tumors. Of these specimens 7 were malignant melanomas, 3 sarcomas and 1 adenocarcinomao Tissue prostaglandin E2 content was higher in malignant compared to normal which also was true when paired differences were analyzed. These findings support the view that prostaglandins may have a role in cell proliferation and/or vascular supply to tumor tissues. The hypothesis also was discussed that prostaglandin E2 may represent a tumor against host defense, since it can decrease spontaneous and antibody-dependent cytotoxProstaglandin E2 also may have a role in tumor-induced osteoporosis and hypercalcemia. If this hypothesis is correct prostaglandin E2 synthesis inhibitors may be used as auxiliary antitumor agents. P. M. H. 2 30 references
A Small Molecular Weight Growth. Inhibitory Factor in Tissue Cultm·e Supernatants
L J.
Catholic Medical
14: 415-432, 1983
substances of cellular origin have been as chalones or as acid inhibitors. Most of the latter substances were found in supernatants of established normal human cell lines. This is based on the common observation that growth of mammalian cells in tissue cultures decreases and eventually stops as the concentration of cells increases. Optimal growth usually occurs between the low and high cell concentrations. Bacterial growth often follows the same pattern. This phenomenon commonly is attributed to contact inhibition owing to the increased proximity of the cells in concentrated cultures. The author considers the hypothesis that decreased growth may be owing to synthesis of a growth-retarding material by the cells themselves or the gradual accumulation in the medium of a growth-retarding agent, normally produced and released by the cells but effective only when reaching a critical concentration in the surrounding extracellular milieu. The author found a small molecule in tissue culture supernatants
with UHH,,,v,n effects on the parent and other cells. Supernatants from stationary phase cultures of a human normai cell line inhibited the of the parent cells even when the latter were in optimal concentrations. Inhibitory activity was associated with small molecular weight fractions prepared by filtration. Fractions with materials <5,000 daltons were the most active. Growth inhibition also was observed with fractions <1,000 daltons. Similar growth inhibition of parent cells was observed with the small molecular weight fractions of supernatants from the human acute lymphoblastic leukemia cell line CCRF-SB, the human lung cancer cell line A-549 and a mouse leukemia SL-1210 line. The study demonstrates that supernatants from tissue cultures with high cell concentrations failed to support the growth of the parent cells even when the latter are diluted to optimal concentrations. This result cannot be explained by crowding alone nor by a lack of nutrients in the medium used. Complete inhibition of growth with the most active fractions was associated with death of most cells in the test culture. Usually, the cells were viable at 24 hours but showed progressively larger numbers of trypan blue permeable cells on subsequent days. Mild inhibition was not associated with extensive cell death and the cultures eventually caught up with the controls. Differentiation of growth inhibition from cytotoxicity can be extremely difficulto P M. H. 6 tables, 17 references Antitu.mor Studies of 2-Amim::i-2-Thiazoi.i.ne and Other Tumor-Modifying Agents
J. PINE, E. A. MIRAND, Jo L. AMBRUS AND F. G. BOCK, Departments of Experimental Therapeutics, Biological Resources and Pathophysiology, and Orchard Park Laboratories, Roswell Park Memorial Institute, Buffalo, New York
M.
Jo Med., 14: 433-449, 1983 Recently, interest has developed in the use of biological modifiers of tumors as antitumor agents. Puck originally proposed the concept of reverse transformation of transformed cells via restoration of normal membrane and organelle structure. The re-establishment of high intracellular levels of cyclic adenosine 3',-5'-monophosphate was considered paradogmatic of this effect. The authors examined 2-amino-2-thiazoline and as antitumor agents in several rodent tumor systems. 2-Amino-2-thiazoline administration reduced tumor incidence in outbred ICR Swiss female mice and doubled the survival of leuRA233 and diean.cuoui; host or tumor prostaglandin levels, platelet aggregation and host immunity, respectively, ranged from marginally effective to ineffective against Friend virus infection. However, 2-amino-2-thiazoline was ineffective against 4 other induced and transplanted mouse tumors, and did not increase differentiation or decrease transformation notably in any of several tumor cell systems. No in vitro or in vivo tumor system was found to be more than marginally affected by l-thiazolidine-4-carboxylate. Thus, 2amino-2-thiazoline alone had significant antitumor activity in inhibiting late stages of viral-induced or carcinogen-induced tumor progression but could not be demonstrated as an agent of reverse transformation. 2-Amino-2-thiazoline has been of commercial use as a photographic developer and may function as a biological antioxidant. However, it is unlikely that this