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1.
Photofrin uptake by murine macrophages 总被引:2,自引:0,他引:2
The uptake of Photofrin by murine peritoneal macrophages in vivo and in vitro was examined. Cellular Photofrin content was measured either by performing a fluorometric assay or by using 14C-labeled drug. For comparison, the uptake of Photofrin by murine SCCVII tumor cells (squamous cell carcinoma) was also examined under the same conditions. The data demonstrate that macrophages have a much greater capacity for Photofrin uptake than SCCVII tumor cells. Photofrin contents at 24 h after drug administration (25 mg/kg) measured 420 +/- 90 (SD), 74 +/- 15, and 15 +/- 2 ng/micrograms of cell protein for peritoneal macrophages, tumor-associated macrophages, and SCCVII tumor cells, respectively. Factors that modify macrophage activity also influence the uptake of the drug by macrophages. The results support the assumption that Photofrin uptake by macrophages is dominated by phagocytosis of highly aggregated components of the drug. In vivo accumulated Photofrin material in peritoneal macrophages, tumor-associated macrophages, and tumor cells has shown very similar in vitro clearance from all three cell types. Only 20-30% of Photofrin was lost from the cells during the initial 24 h, mainly between 1 and 4 h of clearance incubation. 相似文献
2.
Multiple tumoricidal effector mechanisms induced by adriamycin 总被引:3,自引:0,他引:3
The antitumor cytotoxic mechanisms of Adriamycin-elicited peritoneal exudate cells were investigated. Peritoneal exudate cells from mice collected 1 day after an i.p. injection of Adriamycin (10 mg/kg) displayed enhanced cytotoxicity against P815 (natural killer-insensitive, macrophage-sensitive) but not YAC-1 (natural killer-sensitive) tumor cell lines. These cells contained a sufficient concentration of the drug to be cytotoxic for P815 tumor cells in 18-hr chromium release assays. Freeze-thaw lysates of these peritoneal exudate cells were found to be as cytotoxic to P815 as their corresponding whole cells. The lytic activity of these lysates was removed by centrifugation at 100,000 X g, indicating the insolubility of the effector moiety. These cells were also shown to produce significant amounts of superoxide anion and H2O2 in response to phorbol myristate acetate. A catalase-inhibitable augmentation of the cytotoxicity of these cells against P815 was observed when phorbol myristate acetate was added to the assay. Neutrophils and not macrophages were likely responsible for this effect. Peritoneal lymphocytes from mice given injections of Adriamycin 5 to 7 days previously were cytotoxic to YAC-1 tumor cells in 4-hr assays. Finally, peritoneal macrophages harvested 5 to 7 days after Adriamycin administration were cytotoxic to P815 in the absence of detectable Adriamycin. The addition of phorbol myristate acetate inhibited the lysis of P815 by these cells. 相似文献
3.
H U Schorlemmer W Opitz E Etschenberg D Bitter-Suermann U Hadding 《Cancer research》1979,39(5):1847-1853
Treatment of NMRI mice i.p. with dehydrodipeptides [acetyldehydro-3-(2-thienyl)alanyltyrosine (SI); acetyldehydro-3-(2-furyl)alanyltyrosine (SII)] rendered macrophages cytolytic for several tumor cells in vitro. Normal peritoneal mouse macrophages from untreated mice not given injections of the peptides or from control mice given injections of phosphate-buffered saline were not cytotoxic. Moreover, supernatants from these in vivo-activated mouse peritoneal macrophages significantly increased the release of the cytoplasmic enzyme lactate dehydrogenase from freshly added target cells, showing that these cells had been killed. The macrophage activation to lyse tumor cells was sharply dose dependent and appeared about 48 hr after injection of the peptides. Although dehydrodipeptide SI was active in vivo at concentrations as low as 500 microgram/mouse, the same substance lacked activity in vitro at all concentrations tested up to 800 microgram/ml. Dehydrodipeptides activate macrophages through a T-cell-independent process to lyse tumor target cells. Macrophages from athymic nude (nu/nu) mice were less cytotoxic, but they still were stimulated; and the culture supernatants could kill about 50% of the tumor cells used. There are indications for a relative specific structure-activity relationship of dehydrodipeptides for inducing cytotoxic macrophages. 相似文献
4.
An investigation was carried out to determine the potential for activating tumor-inhibitory macrophages with the cytotoxic antitumor agent, bisantrene. Macrophages prepared from peritoneal exudates of mice treated i.p. with bisantrene were extremely active in inhibiting the growth of tumor cells. The minimal effective in vivo dose of this drug appeared to be 25 mg/kg, with peak activation being achieved at doses of 50 to 100 mg/kg. Effector cells became detectable 2 days after treatment and persisted for at least 4 weeks. Incubation of effector and target cells for 48 hr seemed necessary to achieve the maximum inhibitory effect. Treatment with carrageenan in vitro and in vivo abolished tumor cytostasis, whereas treatment with anti-T-cell antibody plus complement had no effect, suggesting that macrophages rather than T-lymphocytes were responsible for the observed results. Culture supernatants of activated macrophages were found to have antiproliferative effects on tumor cells, indicating that a cytostatic factor(s) was produced by these macrophages. Hydrogen peroxide and neutral proteases apparently did not function as cytostatic mediators since activated macrophages were resistant to treatment with catalase, N-alpha-p-tosyl-L-lysine chloromethyl ketone, and aprotinin. The present findings suggest that, in addition to direct toxicity to tumor cells, bisantrene may act as a macrophage-activating immunopotentiator. This observation may be of potential clinical usefulness in the design of immunochemotherapeutic trials for certain types of cancer. 相似文献
5.
The in vitro cytotoxicities of the four drugs most frequently used for intravesical chemotherapy (Adriamycin, epodyl, mitomycin C, Thiotepa) and epirubicin were compared using monolayers and multicellular tumor spheroids of the human bladder cancer cell line, MGH-U1. Adriamycin and epirubicin were most cytotoxic against monolayer cultures, whereas mitomycin C killed more cells in spheroids. Epodyl was least cytotoxic against both two- and three-dimensional cultures. Thiotepa was the only drug more cytotoxic to three- than two-dimensional cultures. Topographic analysis of bromodeoxyuridine-stained nuclei using image analysis indicated that Adriamycin selectively removed or killed superficial cells in multicellular tumor spheroids, but had little effect on DNA synthesis within the spheroids. In contrast Thiotepa killed cells throughout the spheroids. These in vitro data appear to reflect clinical experience using intravesical chemotherapy to treat superficial bladder cancer. 相似文献
6.
H F Dullens R A De Weger R A Woutersen W Den Otter 《Journal of the National Cancer Institute》1975,54(1):77-82
Goat-antimouse (DBA/2) SL2 lymphoma immunoglobulin was specifically cytotoxic to DBA/2-derived sl2 lymphoma cells. This anti-SL2 immunoglobulin, or a part of it, was cytophylic for peritoneal macrophages as shown by target cells adhering to macrophages incubated in vitro with the immunoglobulin. The target cells became free in the medium after incubation with 0.1% trypsin for 1 hour. In in vivo experiments, the incubation of immune or hyperimmune peritoneal cells with immunoglobulin from normal goat serum or from goat-anti-SL2 serum before use in immunotherapy decreased the number of DBA/2 mice surviving for more than 35 days an intraperitoneal injection with SL2 cells compared to the number of survivors inoculated with immune or hyperimmune cells only. These results show that, in immunotherapy with immune cells, we must consider the possibility that specific antitumor antibodies and antibodies not directed against the tumor cloud the therapeutic potnecy of the immune cells. 相似文献
7.
J Stanková 《International journal of cancer. Journal international du cancer》1992,51(2):259-265
Anti-CD3 antibody induced non-MHC-restricted cytolytic activity in murine spleen cells within 4 hr of incubation in vitro and within 8 hr in vivo after intraperitoneal injection. Interstitial lung leukocytes acquired the capacity to kill both NK-sensitive and -resistant targets within 24 hr after anti-CD3 injection. In vivo-stimulated spleen cells produced significantly more IL-2 and TNF than unstimulated cells. When these cells were restimulated with anti-CD3 in vitro, a potentiation of TNF production was seen. Interstitial lung leukocytes doubled their TNF production ex vivo after anti-CD3 injection, and the suppressed TNF production which was seen in lung cells from tumor-bearing animals was restored after anti-CD3 stimulation. The TNF production by alveolar macrophages was augmented 5-fold 48 hr after injection of antibody. Anti-CD3 antibody also induced significant accumulation of both TNF alpha and TNF beta mRNA in spleen and lung leukocytes. Pre-treatment with anti-TNF antibodies, both in vitro and in vivo, did not eliminate the cytolytic activation of lung and spleen cells. Our data indicate that anti-CD3 antibodies can induce rapid activation of both cytolytic activity and cytokine production in lung lymphocytes and macrophages. 相似文献
8.
R Raijmakers P Speth T de Witte P Linssen J Wessels C Haanen 《British journal of cancer》1987,56(2):123-126
The effect of adriamycin (ADM) infusion-rate on cellular ADM concentrations and on clonogenicity of human haematopoietic cells was studied in vivo and in vitro. In patients an ADM dose of 30 mg m-2 was administered as a bolus injection, or as a 4 h or a 24 h infusion. In vitro the effect of ADM on clonogenic cell growth was determined after exposure during 5 min, 2 h and 24 h of human bone marrow cells to increasing ADM concentrations. ADM showed rapid intracellular accumulation, to levels 100-fold the plasma concentration in vivo or the incubation medium concentration in the in vitro experiments. After a bolus injection or 5 min exposure only approximately 10% of the cellular peak ADM was retained after elimination of the drug from the plasma or the incubation medium. Ninety percent of the ADM was apparently 'loosely' bound. After 4 h and 24 h constant-rate infusions and also after 2 h and 24 h incubations in vitro, the cells accumulated ADM gradually, and the subsequent washing-out of the cellular ADM was substantially less, most of the ADM being 'tightly' bound. Despite these different patterns of uptake and retention after in vivo short- and long-lasting infusion of the same total dose, the 'tightly-bound' cellular ADM concentrations were the same. Moreover, comparable cellular ADM concentrations, retained after efflux of the 'loosely-bound' cellular ADM fraction were equally cytotoxic to normal human clonogenic cells. Short-lasting cellular peak ADM concentrations which occur after a bolus injection or after short exposure to high ADM concentrations are not essential for the cytotoxic effect, in contrast to the retained, 'tightly-bound' cellular ADM levels. 相似文献
9.
A Sood B F Spielvogel B R Shaw L D Carlton B S Burnham E S Hall I H Hall 《Anticancer research》1992,12(2):335-343
The guanine, inosine, adenine and cytidine deoxyriboside cyanoboranes proved to be cytotoxic and possess in vivo antineoplastic activity against murine and human single cells and cultured cells derived from solid tumor lines. The agents preferentially inhibited DNA synthesis in Tmolt3 leukemic cells. The enzyme sites of drug inhibition of two active derivatives were DNA polymerase-alpha and de novo purine synthesis at the regulatory sites, PRPP amido transferase and IMP dehydrogenase. Moderate inhibition by the agents of TDP kinase and ribonucleoside reductase activities also occurred. Kinetic studies showed that IMP dehydrogenase activity was inhibited the earliest of all of the enzymes affected by the drugs. The d(ATP) pools were also reduced by drug treatment. DNA strand scission was evident after 24 hr incubation at 100 microM of drug. The 14C-cytidine-cyanoborane drug was rapidly taken up over 6 hr and most effective uptake was shown by rapidly dividing cells. The drug was bound to DNA, RNA and protein in Tmolt3 leukemic cells. 相似文献
10.
Normal resident peritoneal macrophages from BALB/c mice were continuously grown and expanded in vitro as non tumorigenic cells on a confluent layer of mesothelial cells. These peritoneal macrophages expanded in vitro (EPM) were very cytotoxic against EMT6 sarcoma, Abelson myeloma, EL4, and L929S cells in culture. This tumoricidal effect was fully expressed without further activation with bacterial lipopolysaccharides (LPS). In vivo, adoptive transfer of one million EPM to BALB/c mice bearing subcutaneous EMT6 sarcoma caused regression of the solid tumor. In contrast, macrophages produced by 10 days' culture of bone marrow stem cells, or freshly isolated from the peritoneal cavity of BALB/c mice, were not cytotoxic in vitro or in vivo. Local injection in the vicinity of the tumor as well as intravenous transplantation of EPM effectively inhibited tumor growth. This antitumoral effect was further enhanced by intraperitoneal injection of 2 micrograms LPS to the tumor bearing mice. 相似文献
11.
We report alkaline elution experiments that reveal the temperature dependence of DNA lesions, both single-strand breaks and DNA-protein cross-links, in L1210 cells exposed to Adriamycin. DNA damage, which at 37 degrees C is equivalent to several hundred rads of ionizing radiation exposure, diminishes as the temperature of drug exposure is lowered. At all temperatures below about 15 degrees C no DNA damage is detectable in L1210 cells exposed to Adriamycin, even at relatively high doses. The low temperature inactivity is not due to a redistribution of intracellular drug since at both 37 and 0 degrees C there is a high concentration of Adriamycin in both nuclear and cytoplasmic locations. The temperature profile for DNA damage parallels the profile for cytotoxicity, i.e., at low temperature, the drug is completely inactive as a cytotoxic agent (P. Lane, P. Vichi, D. L. Bain, and T. R. Tritton, Cancer Res., 47:4038-4042, 1987). Thus, DNA breaks and cell kill appear to be correlated with one another. However, when we examined DNA lesions in nuclei isolated from L1210 cells we found that the low temperature inability to sustain Adriamycin-induced single-strand breaks or DNA-protein cross-links was absent. In nuclei, then, the drug can provoke DNA damage at low temperature, while in whole cells it cannot. Topoisomerase II, an enzyme implicated in catalyzing DNA lesions in cells exposed to intercalating agents, retains its catalytic activity both to unknot P4 DNA at 0 degrees C, and to be induced by drug to alter the release of pBR322 supercoils, so a low temperature inactivation of this enzyme cannot explain the results. We propose that intact L1210 cells have a regulatory factor which controls DNA damage, possibly through topoisomerase II, but which is lost when nuclei are isolated. 相似文献
12.
Ikehara Y Niwa T Biao L Ikehara SK Ohashi N Kobayashi T Shimizu Y Kojima N Nakanishi H 《Cancer research》2006,66(17):8740-8748
The lymphoid tissue in the omentum, at the so-called milky spots, is known as an initial place for disseminated cancer cells to develop into solid tumors. In the present study, i.p. macrophages significantly took up oligomannose-coated liposomes (OMLs) that were injected into the peritoneal cavity, and then gradually accumulated in the omentum and the other lymphoid tissues within 24 hours of i.p. injection of OMLs. When 5-fluorouracil (5-FU) was encapsulated in the OMLs, >60% of administered 5-FU accumulated in the omentum. Treatment of macrophages at 39 degrees C for 30 minutes led to the release of 5-FU from the macrophages, suggesting that controlled release from macrophages could be achieved by mild hyperthermia. We encased magnetic nanoparticles, which are known to convert electromagnetic energy to heat in the OMLs to achieve in vivo hyperthermia at the site. Using this system in a mouse i.p. metastasis model, we successfully controlled tumor development by coadministration of OML-encased 5-FU and OML-encased magnetic nanoparticles, followed by treatment with an alternating magnetic field. No apparent reduction was seen in tumor growth with the administration of OML-encased magnetic nanoparticles or OML-encased 5-FU alone. Thus, we have established the use of i.p. macrophages as a novel drug delivery system for the control of cancer metastatic to milky spots. 相似文献
13.
Cytotoxicity of adriamycin in MGH-U1 cells grown as monolayer cultures, spheroids, and xenografts in immune-deprived mice 总被引:1,自引:0,他引:1
The cytotoxic activity of Adriamycin was examined in the MGH-U1 human bladder carcinoma line, grown as monolayer culture, as spheroids, and as xenografts in immune-deprived mice. The MGH-U1 cells grown as spheroids were much more resistant to Adriamycin (concentration of drug resulting in 37% cell survival, 4.5 micrograms/ml) than when treated as monolayer cultures (concentration of drug resulting in 37% cell survival, 0.9 microgram/ml). Adriamycin fluorescence was demonstrated only in the outer two layers of cells forming the spheroids, suggesting that limited drug penetration is an important factor in the resistance of spheroids to Adriamycin. Sequential trypsinization of spheroids 750 micron in diameter allowed us to determine the cytotoxic effects of Adriamycin in MGH-U1 cells derived from different depths of the spheroid. We found that cells near the surface of the spheroid had a survival similar to those of exponentially growing monolayer cells treated with Adriamycin. Cells located in the middle of the viable rim were more resistant to Adriamycin, and those found near the necrotic center were most resistant to Adriamycin. The effects of Adriamycin treatment on spheroid growth delay were determined also. In spite of a small cytotoxic effect on the clonogenic fraction of cells in MGH-U1 spheroids, the growth delay effect of Adriamycin in intact spheroids was marked. This observation is consistent with Adriamycin killing primarily the cells in the outer layers of the spheroid, where most of the proliferation in the spheroid occurs. In vivo treatment of MGH-U1 xenografts with Adriamycin followed by assessment of cell survival in vitro showed minimal evidence of cytotoxicity, consistent with the poor drug penetration observed in the spheroid model. These studies suggest that: (a) Adriamycin penetrates poorly into solid tissues; (b) in vitro clonogenic survival following Adriamycin exposure of a cell suspension may predict falsely for drug sensitivity to chemotherapy; (c) a small decrease in clonogenic survival can be translated into a long growth delay but, ultimately, the tumor regrows because some clonogenic cells are spared; and (d) for Adriamycin, the spheroid model more closely parallels the in vivo effects than does monolayer culture. The use of the spheroid model for the study of Adriamycin cytotoxicity gives further insight into the action of this drug in solid tumors. 相似文献
14.
The antibiotic protein auromomycin (AUR) is composed of a chromophore and an apoprotein. The in vitro cytotoxic activity of AUR is associated with the chromophore, whereas the apoprotein is not cytotoxic. Exposure to AUR blocks cell cycle traverse in G2-M phase. Both AUR and the chromophore exhibit antitumor activity against murine L1210 leukemia, both in vitro and in vivo. Similarly, neocarzinostatin and its chromophore also show antitumor activity against L1210 tumor cells in vitro and in vivo. AUR and neocarzinostatin apoproteins have no antitumor activity. The pharmacokinetics of 125I-labeled AUR in L1210 tumor-bearing mice shows a triexponential drug decay and initial rapid clearance of drug from the blood. The distribution of AUR-associated radioactivity into various tissues is rapid, and at the end of 24 hr, there is little drug accumulation in the tissues. During the first hr, greater than 50% of the administered drug is eliminated in the urine. As the chromophores alone possess antitumor activity, the effect of these antitumor proteins in cancer chemotherapy might be significantly increased by the administration of protein preparations containing biologically active and stable chromophores. 相似文献
15.
H Aso F Suzuki T Yamaguchi Y Hayashi T Ebina N Ishida 《Gan to kagaku ryoho. Cancer & chemotherapy》1982,9(11):1976-1980
After oral administration of an organic germanium compound, Ge-132 (300 mg/kg), a significant level of interferon (IFN) activity was detected in the sera of mice at 20 hr and it reached a maximum of 320 U/ml at 24 hr. This IFN activity was lost after heat- or acid-treatment, suggesting that the induced IFN is of gamma nature. The molecular weight of this IFN was estimated to be 19,000 daltons by gel filtration. After the oral administration of Ge-132, NK activity of spleen cells had increased at 24 hr and cytotoxic macrophages were induced in the peritoneal cavity at 48 hr. In mice, receiving intraperitoneal (i.p.) injections of trypan blue or carrageenan 2 days before oral administration of Ge-132, neither induction of IFN nor augmentation of NK activity followed. X ray irradiation of mice also rendered the mice incapable of producing IFN, all suggesting that both macrophages and lymphocytes are required for this IFN induction. After i.p. administration of induced IFN, both NK and cytotoxic macrophage activities appeared at 48 hr with as little as 20 U/ml titered IFN. These facts may indicate that the augmentation of NK and activation of macrophages in mice after oral administration of Ge-132 is mediated by induced IFN. 相似文献
16.
Hypoxic Chinese hamster V-79 cells were examined for light-microscope morphology, progression through the cell cycle, chromosomal aberrations, and viability, after incubation with the 2-nitroimidazole, misonidazole [1-(2-nitro-1-imidazolyl)-3 methoxy-2-propanol]. Cytological examination of cells up to 42 hr after incubation with the drug at 37 degrees indicated that increasing contact time and increasing drug concentrations interfered with cell attachment and progressively slowed cell progression through the cell cycle. Forty-two hr after a 5.5-hr treatment with 5 mM misonidazole, the majority of cells contained heteropyknotic nuclei, whereas less than 3% had progressed into mitosis. Of the few cells that reached mitosis by 42 hr, the level of chromosomal aberrations was 6 times that due to hypoxia alone. However, the majority of metaphases (70%) were unaltered; thus about 2% of the treated cell population passed into mitosis unaltered. After a 5.5-hr incubation with 5 mM misonidazole, 98% of the cells also had lost their ability to produce clones. It is suggested that the cytotoxic effect of this drug on hypoxic cells is that the cytotoxic effect of this drug on hypoxic cells is largely mediated via an interphase cell death, with a minor effect due to chromosome aberrations and cell death from genetic inequality of progeny cells. The ability of misonidazole to kill hypoxic, noncycline cells, which may limit the curability of some tumors with conventional X-rays or chemotherapy agents, makes it of considerable potential interest. 相似文献
17.
J A Stolwijk J M Minke G R Rutteman J Hoekstra F J Prop W Misdorp 《Anticancer research》1989,9(4):1045-1048
Feline mammary carcinomas were tested for their in vitro and in vivo sensitivity to Adriamycin. In vitro, twenty randomly chosen tumor islands were studied to test the effect of concentrations of the drug ranging from 0.25-2.00 micrograms/ml. In vivo, parts of primary tumors left in situ after surgical biopsy were used to assess the response to five i.v. injections of 30 mg/m2 Adriamycin. When comparing the in vitro and in vivo response, the best sensitivity (100%) was obtained using 2.00 micrograms/ml Adriamycin and the best specificity (75%) using 1.00 microgram/ml Adriamycin, both in vitro. Tumors recurring after treatment showed acquired resistance in vitro. 相似文献
18.
Adriamycin is a cytotoxic drug which has enjoyed considerable success in the treatment of cancer. This agent has a bewildering variety of biological effects both within and on the surface of cells exposed to drug, and it has proved difficult to unambiguously assign a single mechanism of action. In this report we are able to separate intracellular and extracellular actions by taking advantage of the complete lack of Adriamycin-induced cytotoxicity at low temperature. For example, cells exposed to 100 microM Adriamycin at 0 degree C are not killed by the drug, even though this concentration is orders of magnitude higher than the concentration needed to cause 100% cell death at 37 degrees C. If cells exposed to 100 microM Adriamycin at 0 degree C are shifted to fresh drug-free medium at 37 degrees C, there is a time-dependent decrease in survival. However, if the drug-free medium contains calf thymus DNA (1.5 mg/ml) to act as a reservoir for Adriamycin binding of effluxed drug, there is no ensuing cytotoxicity. Thus, the results show that no matter how much drug is present inside the cell, there must also be extracellular drug available for membrane interaction in order to initiate nuclear DNA damage and the cytotoxic cascade. 相似文献
19.
Two naturally occurring cytotoxic cell populations have been identified in the peritoneal cavity of mice inoculated with C. parvum (CP), and are distinguishable on the basis of target-cell reactivity and intrinsic properties. The first effector cell was non-adherent to nylon wool and glass and non-phagocytic. These cells were selectively cytotoxic to the NK-sensitive target cell line K562, and present in the peritoneal cavity of mice 2 days after treatment with 700 micrograms of CP. The second cytotoxic effector cell was adherent to nylon wool and glass, and killed EL4 lymphoma cells derived from in vivo tumour transplants; these target cells are susceptible to phagocytic cell killing, but not NK-cell cytotoxicity in short-term (4h) assays. The adherent cytotoxic population of effector cells was present 4 days after inoculation of CP. In vivo studies showed that CP injected i.p. induced resistance to i.p. challenge with lymphoma EL4 cells, but no resistance was evident when the challenge dose was administered s.c. Adoptive-transfer studies showed that the effector cell type responsible for inhibiting tumour growth was nylon-wool adherent, probably CP-activated macrophages. 相似文献
20.
Augmentation of the generation of cell-mediated cytotoxicity after a single dose of adriamycin in cancer patients 总被引:2,自引:0,他引:2
The effect of Adriamycin on the generation of cell-mediated cytotoxicity in the mixed cell culture was studied in patients with various carcinomas. Peripheral blood mononuclear cells (PBM) from the patients were cultured with the B-lymphoblastoid cell line Raji in mixed culture, and the induced cytotoxicity was measured by 51Cr release assay. In patients with various carcinomas, the capacity of PBM to be converted to cytotoxic cells was significantly augmented 5, 7, and 10 days after a single dose of 25 mg/sq m i.v., when compared to that of PBM obtained before Adriamycin injection. The peak level of the cytotoxicity observed 7 days after injection was more than 2-fold higher than that before treatment. Although the depletion of adherent cells from PBM either before or after treatment resulted in a decreased cytotoxic response, nonadherent cell fractions as well as unfractionated cells from PBM after drug treatment equally showed an augmented response when compared to that before injection. The distribution of T-cell subsets exhibited a significant increase in the percentage of OKT8 positive cells after administration. Furthermore, PBM obtained after treatment produced significantly higher levels of interleukin 2. The results appear to indicate that the imbalance of T-cell subsets and the increase of interleukin 2 production may be related to the augmenting effect of Adriamycin administration on cytotoxic response in cancer patients. 相似文献