1
in part from intcmal calcium stores. Desensitization toasecondaddition of active bombcsin congencrs occurs subsequent to initial addition of Tyfl-bombcsin. Structure-activity analysis showed the carboxyl-termi- nal octapcptide was the active portion of the peptide. Analogs in which the carboxyl terminus was oxidized or deamidated were inactive. Ranatensin, litorin, alytcsin, and GRP, but not physalaemin, were as active as Ty?-bombesin. A monoclonal antibody to the carboxyl terminus of bombesin selectively blocked the increased [Ca’+](O elic- ited by TyP-bombesin. These studies suggest that bombesin congcncrs can act on some small cell lung cancer cell lines by a pathway utilizing increased [Ca2*](i). Comparison of chrysene metabolism in epithelial human bronchial and Syrian hamster lung cells. Jacob J, Grimmer G, Raab G, Emura M, Riebe M, Mohr U. Biochem- isches tnstitut fur Umweltcarcinogene. 2070 Ahrensburg-Grosshans- dorf Cancer Lett 1987;38:171-80. Chrysene is metabolized to I-, 2-, 3-, and 4-hydroxychrysene and trans-l ,2- as well as trans-3.4.dihydroxydihydrochrysene in human and Syrian hamster epithelial lung cells as indicated by GC/MS analysis, whereas K-region oxidation is at most a very minor pathway. Cells of a permanent clonal line of fetal hamster lung metabolized 97% of the chrysene whereas fetal human bronchial cpithelial cells converted 24% of the substrate within 8 days incubation. In human cells oxidation at the 3,4-position predominates, whereas oxidation at the 1.2~position is the major pathway in hamster cells. Indication for a bay-region of chrysene in hamster cells has been obtained. Influence ofdocosahexaenoic acid in vitro on intracellular adriamy- tin concentration in lymphocytes and human adriamycin-sensitive and -resistant small-cell lung cancer cell lines, and on cytotoxicity in the tumor cell lines. Zijlstra JG, De Vries EGE, Muskiet FAJ, Martini IA,Timmer-Bosscha H, Mulder NH. Division of Medical Oncology, Departmen oftnternal Medicine, Universiry Hospital, 9713 EZ Groningen. Int J Cancer 1987;40:850-6. An increase in the therapeutic effects of cancer chemotherapeu- tic agents and circumvention of drug resistance in cancer cells might result from an increase in the intracellular drug level. Alteration of the lipid domain of the cell membrane can result in a higher intracellular drug level. This alteration was achieved in human lymphocytes and in human adriamycin (ADR)-sensitive and -resistant small-cell lung car- cinoma cells in vitro by incubation with docosahcxaenoic acid (22:6). Incorporation of the fatty acid in cellular phospholipids was measured by gas chromatographic analysis. A significant increase of 22:6 could be reached without lossof viability in all 3 cell types. Incorporation was demonstrated notably in the phosphatidyl choline, phosphatidyl etha- nolamine and phosphatidylserine, and was most pronounced in the phosphatidyl choline of the ADR-resistant line. After a I-hr incubation with ADR, a 10-300/o incrcasc in intracellularadriamycin concentration was found in all 3 cell types previously incubated for 4 days with 22:6. After 1 hr incubation with ADR there was no increase in cytotoxicity in the sensitive cell lint when measured by soft agar clonogcnic assay and a partial reversal (52 to 14) of resistance factor (ratio of drug doses to product 50% growth inhibition) in the resistant cell line. Increasing the time of ADR exposure from I to4 hr further reduced the resistance factor to 8.6. Glucose utilization in vivo by human pulmonary neoplasms. Nolop KB, Rhodes CG, Brudin LH et al.MRC Cyclofron Unit, Royal Poslgraduale ,Medical School, Hammersmi~h Hospital. London WI 2 OHS. Cancer 1987:60:2682-9. Neoplastic tissue in general shows a high rate of glucose consumption under both anaerobic and aerobic conditions. Using positron emission s21 tomography (PET) we measured the rate of uptake of the glucose analogue “fluoro-2-deoxy-D-glucose (‘*FDG) in I2 patients with car- cinema of the lung. The tumor types were six squamous cell, two large cell, two oat cell, one adenocarcinoma, and one undifferentiated carci- noma. In each patient a transaxial plane was selected that contained the bulk of the tumor tissue. Regional density and blood volume were measured. Following the intravenous injection of “FDG, the rates of uptake in the tumor and normal lung tissue were assessed from sequential scansover 1 hour. Ineachpatient therateofuptakeof”FDG in the tumor tissue was significantly increased relative to normal lung tissue. For the group therateofuptakeby thetumor was21 1.4~69.4ml/lOOg/hr(mean * SD) compared to 31.9. 13.2 in the contralateral lung (P < 0.05). The tumor-to-normal tissue ratioof 6.6 (range, 2.7 to 14.6) was higher than previously reported ratios for brain and liver tumors. In contrast to bram tumors there was little correlation between tumor type and rate of ‘*FDG uptake. Measurements of glucose metabolism taken in viva in human pulmonary tumors may lead to advances m screening, staging, and therapy. Secretion of antileucoprotease from a human lung tumor cell line Appelhans B, Ender B, Sachse G, Nikiforov T, Appelhans H. Ebert W. Insliw fur Organ&he Chemie und Biochemie, Technische ttochschule, 6100 Darmsladl. Febs Lett 1987;224: IA-11 Two human tumor cell lines were analyzed for the production of human antileucoprotease (ALP). One of them, a human squamous lung carcinoma cell line (HS-24) synthesized, as confirmed by Western blot analysis, high amounts of ALP in serum-free medium. The supematant inhibited elastase, chymotrypsin and lrypsin. Northern blot analysis with an 18-mer radiolabclled oligonucleotide, dcrivcd from an ALP specific cDNA clone, revealed a specific mRNA of about 700-800 nuclcotidcs in HS-24 tumor cells. In contrast, a secondary human lung tumor cell line (SB-3), derived from the adrenal cortex, did not synthesize ALP when assayed under identical conditions. The supema- tant inhibited only trypsin and chymotrypsin. Antitumor activity of pleural cavity macrophages and its regulation by pleural cavity lymphocytes in patients with lung cancer. NagashimaA,YasumotoK,NakahashiH.TakeoS, YanoT,NomotoK. Departmen of Surgery II, Faculty of Medicine, Kyushu Universiry, Higashi-ku, Fukuoka 812. Cancer Res. 1987;47:5497-500. Antitumor activities of pleural cavity macrophages (PCM) and pleural cavity lymphocytes (PCL) in lung cancer patients were exam- ined. Theeffect ofcoculture supematantsof PCL and autologous tumor cells on the cytostatic activity of macrophages was also examined. Cytostatic activity of PCM was not affected by an advance of metastasis to regional lymph nodes or increase of tumor size and difference of histological type. However, the cytostatic activity of PCM was mark- edly augmented when pleural invasion was limited to within the visceral pleuraalthough it was low when pleural invasion wasabsentorextended beyond the visceral pleura. On the other hand, PCL did not exert any cytolytic activity against various tumor target cells. However, coculture supcmatants of PCL and autologous tumor cells exhibited the activity of macrophage-activating factor against guinea-pig peritoneal macro- phagcs. Furthermore, the higher the cytostatic activity of PCM, the higher the macrophagc-actlvatmg factor activity of the coculture super- natant of PCL and autologous tumor cells was. These results suggested thatantitumoractivityofPCM wascontrolledby specifically sensitized PCL through lymphokines. Occurrence of a multidrug-resistant phenotype in human lung xenografts. Mattcm J. Bak M,Volm M. Department of Experimental Parhology. German Cancer Research Cenrer, D-6900 tteidelberg. Br J Cancer 1987:56:407-l 1. The intrinsic sensitivity of a panel of 8 human epidcrmoid lung cancer

Antitumor activity of pleural cavity macrophages and its regulation by pleural cavity lymphocytes in patients with lung cancer

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Page 1: Antitumor activity of pleural cavity macrophages and its regulation by pleural cavity lymphocytes in patients with lung cancer

in part from intcmal calcium stores. Desensitization toasecondaddition of active bombcsin congencrs occurs subsequent to initial addition of Tyfl-bombcsin. Structure-activity analysis showed the carboxyl-termi- nal octapcptide was the active portion of the peptide. Analogs in which the carboxyl terminus was oxidized or deamidated were inactive. Ranatensin, litorin, alytcsin, and GRP, but not physalaemin, were as active as Ty?-bombesin. A monoclonal antibody to the carboxyl terminus of bombesin selectively blocked the increased [Ca’+](O elic- ited by TyP-bombesin. These studies suggest that bombesin congcncrs can act on some small cell lung cancer cell lines by a pathway utilizing increased [Ca2*](i).

Comparison of chrysene metabolism in epithelial human bronchial and Syrian hamster lung cells. Jacob J, Grimmer G, Raab G, Emura M, Riebe M, Mohr U. Biochem- isches tnstitut fur Umweltcarcinogene. 2070 Ahrensburg-Grosshans- dorf Cancer Lett 1987;38:171-80.

Chrysene is metabolized to I-, 2-, 3-, and 4-hydroxychrysene and trans-l ,2- as well as trans-3.4.dihydroxydihydrochrysene in human and Syrian hamster epithelial lung cells as indicated by GC/MS analysis, whereas K-region oxidation is at most a very minor pathway. Cells of a permanent clonal line of fetal hamster lung metabolized 97% of the chrysene whereas fetal human bronchial cpithelial cells converted 24% of the substrate within 8 days incubation. In human cells oxidation at the 3,4-position predominates, whereas oxidation at the 1.2~position is the major pathway in hamster cells. Indication for a bay-region of chrysene in hamster cells has been obtained.

Influence ofdocosahexaenoic acid in vitro on intracellular adriamy- tin concentration in lymphocytes and human adriamycin-sensitive and -resistant small-cell lung cancer cell lines, and on cytotoxicity in the tumor cell lines. Zijlstra JG, De Vries EGE, Muskiet FAJ, Martini IA,Timmer-Bosscha H, Mulder NH. Division of Medical Oncology, Departmen oftnternal Medicine, Universiry Hospital, 9713 EZ Groningen. Int J Cancer 1987;40:850-6.

An increase in the therapeutic effects of cancer chemotherapeu- tic agents and circumvention of drug resistance in cancer cells might result from an increase in the intracellular drug level. Alteration of the lipid domain of the cell membrane can result in a higher intracellular drug level. This alteration was achieved in human lymphocytes and in human adriamycin (ADR)-sensitive and -resistant small-cell lung car-

cinoma cells in vitro by incubation with docosahcxaenoic acid (22:6). Incorporation of the fatty acid in cellular phospholipids was measured by gas chromatographic analysis. A significant increase of 22:6 could be reached without lossof viability in all 3 cell types. Incorporation was demonstrated notably in the phosphatidyl choline, phosphatidyl etha- nolamine and phosphatidylserine, and was most pronounced in the phosphatidyl choline of the ADR-resistant line. After a I-hr incubation with ADR, a 10-300/o incrcasc in intracellularadriamycin concentration was found in all 3 cell types previously incubated for 4 days with 22:6. After 1 hr incubation with ADR there was no increase in cytotoxicity in the sensitive cell lint when measured by soft agar clonogcnic assay and a partial reversal (52 to 14) of resistance factor (ratio of drug doses to product 50% growth inhibition) in the resistant cell line. Increasing the time of ADR exposure from I to4 hr further reduced the resistance factor to 8.6.

Glucose utilization in vivo by human pulmonary neoplasms. Nolop KB, Rhodes CG, Brudin LH et al.MRC Cyclofron Unit, Royal Poslgraduale ,Medical School, Hammersmi~h Hospital. London WI 2 OHS. Cancer 1987:60:2682-9.

Neoplastic tissue in general shows a high rate of glucose consumption under both anaerobic and aerobic conditions. Using positron emission

s21

tomography (PET) we measured the rate of uptake of the glucose analogue “fluoro-2-deoxy-D-glucose (‘*FDG) in I2 patients with car- cinema of the lung. The tumor types were six squamous cell, two large cell, two oat cell, one adenocarcinoma, and one undifferentiated carci- noma. In each patient a transaxial plane was selected that contained the bulk of the tumor tissue. Regional density and blood volume were measured. Following the intravenous injection of “FDG, the rates of uptake in the tumor and normal lung tissue were assessed from sequential scansover 1 hour. Ineachpatient therateofuptakeof”FDG in the tumor tissue was significantly increased relative to normal lung tissue. For the group therateofuptakeby thetumor was21 1.4~69.4ml/lOOg/hr(mean * SD) compared to 31.9. 13.2 in the contralateral lung (P < 0.05). The tumor-to-normal tissue ratioof 6.6 (range, 2.7 to 14.6) was higher than previously reported ratios for brain and liver tumors. In contrast to bram tumors there was little correlation between tumor type and rate of ‘*FDG uptake. Measurements of glucose metabolism taken in viva in human pulmonary tumors may lead to advances m screening, staging, and therapy.

Secretion of antileucoprotease from a human lung tumor cell line Appelhans B, Ender B, Sachse G, Nikiforov T, Appelhans H. Ebert W. Insliw fur Organ&he Chemie und Biochemie, Technische ttochschule, 6100 Darmsladl. Febs Lett 1987;224: IA-11

V .

Two human tumor cell lines were analyzed for the production of human antileucoprotease (ALP). One of them, a human squamous lung carcinoma cell line (HS-24) synthesized, as confirmed by Western blot analysis, high amounts of ALP in serum-free medium. The supematant inhibited elastase, chymotrypsin and lrypsin. Northern blot analysis with an 18-mer radiolabclled oligonucleotide, dcrivcd from an ALP specific cDNA clone, revealed a specific mRNA of about 700-800 nuclcotidcs in HS-24 tumor cells. In contrast, a secondary human lung tumor cell line (SB-3), derived from the adrenal cortex, did not synthesize ALP when assayed under identical conditions. The supema- tant inhibited only trypsin and chymotrypsin.

Antitumor activity of pleural cavity macrophages and its regulation by pleural cavity lymphocytes in patients with lung cancer. NagashimaA,YasumotoK,NakahashiH.TakeoS, YanoT,NomotoK. Departmen of Surgery II, Faculty of Medicine, Kyushu Universiry, Higashi-ku, Fukuoka 812. Cancer Res. 1987;47:5497-500.

Antitumor activities of pleural cavity macrophages (PCM) and pleural cavity lymphocytes (PCL) in lung cancer patients were exam- ined. Theeffect ofcoculture supematantsof PCL and autologous tumor cells on the cytostatic activity of macrophages was also examined. Cytostatic activity of PCM was not affected by an advance of metastasis to regional lymph nodes or increase of tumor size and difference of histological type. However, the cytostatic activity of PCM was mark- edly augmented when pleural invasion was limited to within the visceral pleuraalthough it was low when pleural invasion wasabsentorextended beyond the visceral pleura. On the other hand, PCL did not exert any cytolytic activity against various tumor target cells. However, coculture supcmatants of PCL and autologous tumor cells exhibited the activity of macrophage-activating factor against guinea-pig peritoneal macro- phagcs. Furthermore, the higher the cytostatic activity of PCM, the higher the macrophagc-actlvatmg factor activity of the coculture super- natant of PCL and autologous tumor cells was. These results suggested thatantitumoractivityofPCM wascontrolledby specifically sensitized PCL through lymphokines.

Occurrence of a multidrug-resistant phenotype in human lung xenografts. Mattcm J. Bak M,Volm M. Department of Experimental Parhology. German Cancer Research Cenrer, D-6900 tteidelberg. Br J Cancer 1987:56:407-l 1.

The intrinsic sensitivity of a panel of 8 human epidcrmoid lung cancer