Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The functional activity of Moloney murine sarcoma virus (M-MSV)-specific T lymphocytes in vivo was assayed by the i.v. injection of virus-specific T lymphocytes into T cell-deficient "B mice". Virus-specific T lymphocytes generated in mixed lymphocyte tumor cell cultures were transferred i.v. into syngeneic "B mice" injected simultaneously at a distant site with the virus. These experiments indicated that a low dose (1 X 10(6) cultured cells) of infused lymphocytes can afford protection. To define the T lymphocyte subpopulation which was active, Lyt-2+ lymphocytes were selected by "panning" on plastic petri dishes coated with anti-Lyt-2 monoclonal antibody, and Lyt-2- lymphocytes selected by treatment with anti-Lyt-2 monoclonal antibody and complement. The results indicated that a Lyt-2+ lymphocyte-enriched population was more efficient in conferring protection against M-MSV-induced tumors. To investigate if cytolytic T lymphocytes (CTL) alone had a protective effect, a M-MSV-specific CTL clone was transferred in the same model system. The results demonstrated that a M-MSV-specific CTL clone prevented M-MSV-induced tumor growth and also induced the destruction of syngeneic Moloney murine leukemia virus (M-MuLV)-induced MBL-2 leukemic cells in the peritoneal cavity. However, the cell dose required to obtain protection using a CTL clone was higher than that which was effective when mixed lymphocyte tumor cell culture cells were used. To assess the ability of the transferred cells to home and to repopulate the lymphoid organs of the "B mice", the frequency of virus-specific CTL precursors in the spleen was evaluated by limiting dilution analysis. The results indicated that lymphocytes from mixed lymphocyte tumor cell cultures can be recovered from the spleens of "B mice" injected i.v. 25 days earlier. On the contrary, following the transfer of an active CTL clone, a very low frequency (less than 1/200,000 cells) of virus-specific CTL precursors was present in the spleens of recipient animals. The same M-MSV-specific CTL clone did not yield protection against M-MSV-induced tumors or MBL-2 leukemic cells when injected i.v. into M-MuLV tolerant mice.
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PMID:Functional activity in vivo of effector T cell populations. III. Protection against Moloney murine sarcoma virus (M-MSV)-induced tumors in T cell deficient mice by the adoptive transfer of a M-MSV-specific cytolytic T lymphocyte clone. 303 Jul 66

The clonality of tumor cells was studied in a patient with metastasizing hepatocellular carcinoma (HCC). Using hepatitis B virus (HBV) DNA as a genetic marker, the pattern of integration of viral DNA into the tumor cell genome was determined by Southern blot analyses of DNAs extracted from different HCC lesions in the liver and both lungs. All tumor tissues examined were found to have viral DNA integrated into the same site(s) of the cellular genome. This finding provides direct molecular evidence for a monoclonal origin and expansion of malignantly transformed hepatocytes during tumor growth and metastasis. This characteristic is similar to other human cancers associated with viral infections, such as adult T-cell leukemia, Burkitt's lymphoma, or cervical cancer, and is important for our understanding of viral oncogenesis in man.
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PMID:Hepatocellular carcinoma and hepatitis B virus infection: molecular evidence for monoclonal origin and expansion of malignantly transformed hepatocytes. 304 Jul 66

The antitumor activities of two ailanthone derivatives with 15 beta-acyloxy side chains were investigated. The cytotoxic activity of 11 beta, 20-epoxy-1 beta, 11 alpha, 12 alpha-trihydroxy-15-beta-[E)-3-methyl-2-octenoyl) oxypicras-3,13(21)-diene-2,16-dione (SUN2071) and 11 beta, 20-epoxy-1 beta, 11 alpha, 12 alpha-trihydroxy-15 beta-[E)-2-undecenoyl) oxypicras-3,13(21)-diene-2,16-dione (SUN0237) was close to that of bruceantin and vincristine. SUN2071 was shown to be a potent inhibitor of protein synthesis in L1210 cultured cells. When administered i.p. to i.p. inoculated P388 leukemia mice, daily treatment with SUN2071 and SUN0237 significantly increased the lifespan (increases in lifespan in excess of 100% were achieved). These increases were comparable to those achieved with vincristine. The therapeutic ratio of SUN2071 was also close to that of vincristine. However, the compounds were ineffective when administered as a single injection. Daily i.p. treatment with SUN2071 demonstrated significant tumor growth inhibition in mice inoculated s.c. with colon-38 and moderate activity against i.p. L1210 leukemia and i.p. B16 melanoma. The compounds were ineffective when tested against the Lewis lung carcinoma and colon-26. In a preliminary toxicological study, SUN2071 at a therapeutic dose in daily consecutive i.p. injection produced leucopenia.
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PMID:Antitumor activity of novel ailanthone derivatives in vitro and in vivo. 317 49

Batracylin (NSC 320846, BAY H 2049), given ip on days 2 and 9 at a dose 400 mg/kg, inhibited tumor growth completely in 80-100% of mice with early-stage colon adenocarcinoma 38. Therapeutic efficacy against this subcutaneously implanted tumor was retained upon oral administration of Batracylin although, compared to ip treatment, larger doses were required. Batracylin also caused regression of advanced (400 mg) colon 38 tumors. Only modest activity was observed for this compound against P388 leukemia, but P388 sublines with acquired resistance to either adriamycin or cisplatin demonstrated collateral sensitivity. Batracylin currently is undergoing toxicological evaluation by NCI prior to clinical trials.
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PMID:Preclinical antitumor activity of batracylin (NSC 320846). 319 81

The susceptibility of human myeloid and lymphoid leukemic blasts to the lytic action of recombinant interleukin-2 (rIL-2)-generated lymphokine activated killer (LAK) cells was analyzed. With the exception of the K562 cell line, all 9 leukemic cell lines tested were resistant to the natural killer activity of freshly isolated peripheral blood lymphocytes (PBL) from healthy donors but were susceptible to the lytic action of PBL cultured for 3 days in the presence of rIL-2. Of the 32 primary myeloid and lymphoid acute leukemia samples investigated, the great majority were natural killer cell-resistant but were variably sensitive to LAK effectors. Variations in LAK activity were observed according to the donor of PBL, while little or no difference was documented in the capacity to elicit LAK activity of PBL cultured with 100 or 1,000 U of rIL-2/ml. Pretreatment of the leukemic target cells with neuraminidase did not increase substantially their sensitivity to LAK activity. LAK cells generated from the PBL of patients at the onset of the disease or in complete clinicohematological remission lysed Raji cells as efficiently as normal LAK effectors. Finally, LAK cells were capable of abrogating the tumor growth in nude mice of a human leukemic T cell line. These findings demonstrate the susceptibility in vitro and in vivo of human leukemic blasts to the lytic effect of LAK cells and point to a possible clinical exploitment of this new form of adoptive immunotherapy in the management of acute leukemia.
Leukemia 1988 Jan
PMID:In vitro and in vivo susceptibility of human leukemic cells to lymphokine activated killer activity. 325 39

T-cell clone K4L, the cell surface phenotypes of which were Thy-1+, Lyt-1-, Lyt-2+, and L3T4-, was established from the spleen cells of a murine leukemia L1210-immune mouse. Clone K4L was specific for antigen B on L1210, and this antigen was different from antigen A for which the previously reported T-cell clone K7L was specific. K4L possessed cytotoxicity and tumor growth-inhibitory activity against both L1210 and antigen A loss variant, L1210-K7L-, but not against syngeneic tumor P388 or L5178Y. Previously we showed that antigen A was lost frequently for generation of antigen loss variants. In contrast, antigen B was barely found to be lost. When mice were inoculated with L1210 plus a moderate dose of K4L, the tumor grew after initial suppression but this newly emerging tumor was K4L sensitive and was ultimately rejected. The mice initially given L1210 plus K4L attained a high-grade tumor-specific immunity for rejecting the subsequently challenged high-dose (10(7) cells) L1210. This immunity did not involve any bystander antitumor activity against the third party P388 lymphoma that was injected together with L1210 but accompanied the increase in the L1210-specific cytotoxic T-lymphocyte activity. Evidence was provided that the live L1210, the outgrowth of which was inhibited by K4L, induced an effective immune response of radiation-sensitive host lymphocytes including L3T4+ helper T-cells. Taken together, our results show a novel strategy for inducing high-grade host-dependent antitumor immunity by use of a cytotoxic T-lymphocyte clone specific for a stable tumor-specific transplantation antigen.
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PMID:Induction of high-grade tumor-specific immunity in a host using a cytotoxic T-lymphocyte clone specific for a stable tumor antigen on murine leukemia L1210. 326 89

A B16 melanoma clone and four derived subclones exhibiting markedly different tumorigenic and metastatic potentials in young C57BL/6 mice were investigated comparatively to determine relative immunogenicities and capacities to induce humoral and cell-mediated immune responses following subcutaneous injection. All five populations stimulated some production of circulating antibody to a cell surface antigen complex (B16-gp70/80/85) specified by endogenous murine leukemia virus, as well as spleen-cell-mediated cytolytic and cytostatic activity apparently directed to the same antigens, but to varying extents. Immunogenicity and relative capacity to induce immunity were inversely related to tumorigenicity and tumor growth rate but were not obviously correlated with metastatic behavior. There were indications that tumor behavior might be influenced by developing or naturally acquired host immunity. The most rapidly growing clone, G3.26, which was poorly immunogenic and nonmetastatic in young mice, grew more slowly and was markedly metastatic in normal-aged mice in which some natural humoral and cellular responses cross-reactive with B16-gp70/80/85 antigens were detected. Furthermore, the highly immunogenic and normally nonmetastatic clone, G3.15, was appreciably metastatic in mice immunosuppressed by T lymphocyte depletion. In other cases, however, tumor behavior in immunosuppressed and immunopotentiated mice did not consistently indicate a critical role for host immunity in determining metastatic or nonmetastatic activity.
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PMID:Development of host immunity to phenotypically diverse B16 melanoma clones. Implications for tumor growth and metastasis. 343 37

The interaction of 5-fluorouracil and cyclophosphamide in the treatment of L1210 and P388 leukemias was studied using response surface methodology. Single dose treatment of each drug was administered simultaneously or with a 24-hr interval between 5-fluorouracil and cyclophosphamide to the advanced tumors or at various times after L1210 inoculation. While at low doses the action of the combination of the two drugs was greater than expected, there was no therapeutic synergism if the drugs were given together (optimum doses cyclophosphamide 366 mg/kg and 364 mg/kg, respectively, in advanced L1210 and P388 leukemias) or in the early tumor when cyclophosphamide was given 24 hours after 5-fluorouracil. In the advanced tumor, using the regimen employing a 24-hr interval between drugs, therapeutic synergism could be demonstrated (optimum doses 5-fluorouracil 130 mg/kg followed by cyclophosphamide 248 mg/kg in advanced L1210 leukemia and 5-fluorouracil 110 mg/kg followed by cyclophosphamide 263 mg/kg in advanced P388 leukemia). The evidence generated suggested that improved therapy could be found in two separate regions of the treatment space, raising the possibility of more than one mechanism of drug interaction. The location of the optimal treatment depended on the tumor burden at the time treatment was initiated. A shift from one region to the other occurred after 4-6 days of tumor growth when the original inoculum was 10(5) i.p. L1210 cells. Another more obvious conclusion that can be drawn is that treatment was less effective as the tumor became more advanced. The notion that different tumor stages may require different ratios of drugs in a clinically useful combination should receive attention.
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PMID:Combination of 5-fluorouracil and cyclophosphamide in L1210 and P388 leukemias with changes in optimum treatments as a function of the age of the L1210 tumor at first treatment. 344 30

In our search for the mechanisms by which the drug 1-O-alkyl-2-O-methylglycero-3-phosphocholine (AMG-PC) inhibits tumor growth and metastasis, we have detected a metabolite, 1-O-alkyl-2-O-methylglycerol (AMG), in membranes of MO4 mouse fibrosarcoma cells grown in the presence of the drug. Synthetic AMG inhibited the activation of highly purified human protein kinase C by diacylglycerol in the presence of phosphatidylserine. Furthermore, AMG also inhibited the receptor-specific binding of 3H-phorbol-12,13-dibutyrate to human HL-60 promyeloid leukemia cells in a dose-dependent fashion. AMG-PC was not effective or much less so in these assays. We suggest that interaction of the metabolite AMG with protein kinase C may inhibit stimulus-response coupling in tumor cells and may thus potentially contribute to the mechanism by which AMG-PC exerts its anticancer activities.
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PMID:A metabolite of an antineoplastic ether phospholipid may inhibit transmembrane signalling via protein kinase C. 344 75

Pregnancy was considered to aggravate concomitant neoplasia; however, recent observations in humans and experimental animals suggest that on the contrary tumor growth may be unfavorably affected by pregnancy. For this relationship to be investigated, a serially transplantable virus-induced lymphoma was inoculated into female rats of two different strains (WF and SD) in early or in late pregnancy. While all nonpregnant control rats died with lymphoma in 8-10 weeks, 36-75% of rats inoculated with lymphoma cells in the 1st week of pregnancy remained free of tumors, and 20-54% had tumors half the size of those in controls. When lymphoma cells were inoculated in the last week of pregnancy, the protective effect of pregnancy, although less clearly manifested, still resulted in 11% rats free of tumors and 78-91% rats with tumors markedly smaller than those of controls. Nonpregnant rats receiving pregnant rat serum in twice weekly injections grew tumors only 25-60% the size of those in rats receiving sera of nonpregnant rats. In vitro, pregnant rat sera added to the tissue culture media of rat lymphoma (AS line) or human leukemia (MOLT-4) cells resulted in reductions of viable target cells of 67-71%, respectively. The present experiments show that transplanted lymphoma cells that are 100% lethal in nonpregnant rats were totally or partially inhibited in their growth when the recipients were pregnant. Similar inhibiting effects were observed when pregnant rat serum was administered to lymphoma cells in vivo and in vitro. The protective effect against tumor growth was greater during early pregnancy, less accentuated during late pregnancy, and ceased entirely post partum and particularly during lactation, when tumor growth resumed on an accelerated course.
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PMID:Protective effect of pregnancy against transplantation of lymphoma in rats. 346 17


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