Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0684249 (lung carcinoma)
 23,830 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have previously reported that 2',3',5'-tris-O-[N-(2-n-propyl-n-pentanoyl)glycyl]-5-fluorouridine (UK-21), a derivative of 5-fluorouridine (5-FUR), and 1-(6-[N-(2-n-propyl-n-pentanoyl)-glycyl]amino-n-hexylcarbamoyl)-5- fluorouracil (UK-25), a derivative of 5-fluorouracil (5-FU), exert their antitumor activity in mice bearing Meth A or EL4 tumor, while their immunosuppressive effects are mild. In the present study, we examined the effects of these compounds on Sarcoma-180 (S-180), P388, L1210, and Lewis lung carcinoma (LLC) in mice by p.o. administration and i.p.-administration. UK-21 given p.o. showed an antitumor effect against S-180, but it showed virtually no antitumor effects against P388, L1210 and LLC. UK-21 given i.p., on the other hand, strongly inhibited the growth of Meth A tumor at a far lower dose than that for oral administration. The bioavailability of UK-21 given p.o. was suspected to be poor. UK-25 given p.o., in contrast, showed the antitumor effect on all of the tumors employed. The bioavailability of UK-25 given p.o. seemed to be comparable to those of other drugs. These results suggest that UK-21 has the potential for development as a parenterally applicable anticancer drug, and UK-25 has the potential as an oral one.
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PMID:Antitumor activity of two novel low immunosuppressive fluoropyrimidines UK-21 and UK-25. 143 42

4-amino-4-methyl-2-pentyne-1-al (AMPAL), a new irreversible inhibitor of aldehyde dehydrogenase (ALDH) has been assayed for its in vitro and in vivo antitumor activity. In vitro, AMPAL inhibits the proliferation and the ALDH activity of L1210 and RBL5 cell lines. In vivo, AMPAL significantly increases the mean survival time of mice i.p. grafted with leukemia (L1210, P815, MBL2, EL4, RBL5 cell lines) or carcinoma cells (Krebs cell line), without haematopoetic toxicity. No carcinostatic effect was observed against the P388 leukemia and the 3LL Lewis lung carcinoma. A possible relationship between the ALDH isoenzyme activity of the tumor and its sensitivity to AMPAL is discussed in the light of previous reports concerning the role of aldehydes in cell growth control.
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PMID:In vivo antitumor activity of 4-amino 4-methyl 2-pentyne 1-al, an inhibitor of aldehyde dehydrogenase. 251 73

In the present study, some basic effects of Eubacterium lentum (TYH-11), isolated from normal intestinal flora, upon the immune system and various experimental tumor cell lines were investigated. E. lentum showed no direct cytotoxicity against Ehrlich ascites tumor, while Serratia marcescens (TY-142) did show direct cytotoxicity. E. lentum presented striking antitumor activity which differed according to the injection route and time. This strain showed antitumor activity against 11 experimental tumor cell lines including Ehrlich ascites tumor, Meth-A, etc., but not against EL4 or Lewis lung carcinoma. The antitumor activity in this strain was recognized to lie in the cell wall and granular fractions. The effect of this strain on the immune system was studied by using plaque formation and the footpad reaction. When mice received 5 injections of E. lentum, the plaque number increased to treble the control level. Spleen weight was also increased following administration of E. lentum. In normal and tumor-bearing mice immunized with SRBC alone, the footpad reaction was increased significantly to the control level by administration of E. lentum.
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PMID:Antitumor activity and its properties of Eubacterium lentum. 312 99

Photodynamic therapy is currently under investigation as a new form of treatment for solid malignant tumors in animals and in humans. The method involves photosensitization of drugs and fluorescent dyes, such as hematoporphyrin derivative (Hpd), after preferential incorporation by neoplastic cells. In in vitro experiments laser light activation completely destroys Hpd-pretreated EL4 cells. Mice bearing MS-2 fibrosarcoma treated with Hpd and laser light survived indefinitely, in comparison with control animals that were untreated or treated only with Hpd or laser light. In mice bearing the highly metastatic tumors B16 melanoma and Lewis lung carcinoma (LLC) treated with Hpd and laser light delivered through a quartz fiber optic significantly prolonged the median survival time. This therapy was compared with surgical excision of primary tumors and, for superficial nonmetastatic neoplasma MS-2, the photodynamic therapy was more effective than surgery, while for metastatic tumors B16 and LLC, there was no significant difference between the two methodologies. However, phototherapy is much less traumatic to the animals.
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PMID:Photodynamic therapy in vitro and in vivo with hematoporphyrin derivative and laser light. 356 6

The antitumor activity of 7-N-(p-hydroxyphenyl)mitomycin C (M-83) against 7 kinds of ascitic tumors and 4 kinds of solid tumors was compared with that of mitomycin C (MMC). M-83 showed more potent activities than MMC against ascites sarcoma 180, fibrosarcoma Meth 1, sarcoma Meth A, melanoma B-16, leukemia P388 and lymphoma EL4, by a single intraperitoneal injection. Furthermore, M-83 gave markedly higher chemotherapeutic ratio than MMC in these tumor systems. M-83 was also markedly effective against solid tumors of sarcoma 180, Meth 1, Meth A and Lewis lung carcinoma, by a single intravenous injection. M-83 gave lower myelo-suppression than MMC at the doses which gave almost equal inhibition on the tumor growth of solid Meth 1. M-83 and MMC significantly inhibited the growth of HeLa S3 cells. Cell growth was observed at 24 hours after addition of 3 X 10(-3) mM of drugs, but no growth was shown thereafter. M-83 inhibited more strongly the incorporation of the radioactive precursor into DNA than that into RNA or protein at the concentration of 3 X 10(-3) mM.
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PMID:Comparative antitumor activities of 7-N-(p-hydroxyphenyl)mitomycin C (M-83) and mitomycin C. 640 71

Our previous studies indicated that a newly synthesized 5-fluorouridine derivative, 2',3',5'-tris-O-[N-(2-n-propyl-n-pentanoyl)glycyl]-5-fluorouridine (UK-21), revealed its antitumor activity by being converted to 5-fluorouridine (5-FUR) and showed a low level of immunological side effects. However, the bioavailability of UK-21 given orally did not seem to be good. In the present study, we focused on the antitumor and immunosuppressive activities of UK-21 given i.p. to mice. UK-21 suppressed the growth of L-1210, P388 and EL4 leukemias inoculated i.v. into corresponding syngeneic mice and both the growth of Lewis lung carcinoma transplanted s.c. and its subsequent metastasis to the lung. UK-21 showed antitumor activity at doses almost 10 times lower than those of 5-fluorouracil (5-FU). The side effects of UK-21, especially on immune functions, were examined in comparison with those of 5-FUR, 5-FU, and cyclophosphamide (CY) at doses producing comparable antitumor activity. The suppressive effect of UK-21 on IgM and IgG antibody formation in mice immunized with ovalbumin was clearly weaker than that of 5-FUR, 5-FU, and CY. The suppressive effect of UK-21 on thymus weight was markedly weaker than that of 5-FU and CY. The reduction of WBC counts induced by UK-21 was also lower than that produced by any other agent. The results reported herein suggest the strong possibility of UK-21 being developed as a novel anticancer drug with cytotoxic mechanisms different from those of 5-FU. Our study also points to the chemical modification of 5-FUR as a feasible way of developing new anticancer drugs.
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PMID:Novel lowly immunosuppressive antitumor fluorouridine derivative, UK-21: antitumor activity and effect on humoral immune response in mice. 800 54

A component exhibiting toxicity to B cell hybridoma cells was isolated and purified from fetal calf serum (FCS) by immunoaffinity chromatography using a monoclonal antibody (mAb) which reacted with the high-molecular-weight glycoprotein (6B3.Ag) recognized by a mAb, 6B3, to human large cell lung carcinoma cells (HLC-2). The component (FCS-6B3.Ag) was a high-molecular-weight antigen (approximately 1,000,000), consisting mainly of 76,000 subunits. FCS-6B3.Ag showed the same mobility in the pre-beta globulin region as that of 6B3.Ag on electrophoresis in 1.2% agarose gel. When FCS-6B3.Ag was analyzed by double immunodiffusion, it reacted with anti-6B3.Ag antiserum and the precipitin line fused partially with that formed between 6B3.Ag and anti-6B3.Ag antiserum. FCS-6B3.Ag was found to be toxic to hybridoma cells (anti-6B3.Ag, anti-alpha-fetoprotein, anti-carcinoembryonic antigen or anti-C-reactive protein mAb producing cells) specifically in vitro at 5 micrograms/ml. The antigen also strongly suppressed their growth. The toxic effect of FCS-6B3.Ag appeared immediately after addition, and death of the target cells was complete only after 36-48 h. However, the antigen exhibited only weak suppression of Ig-non-secretory mouse myeloma (P3U1), thymic lymphoma (EL4) of mastocytoma (P815) cell growth. Five lots of FCS contained 2.1 to 4.1 micrograms/ml of FCS-6B3.Ag.
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PMID:Identification and purification of a toxic component to B cell hybridoma cells in fetal calf serum. 820 Aug 50

This study investigated the generation of primary tumor-specific CTL activity in vitro to several mouse tumors. We report that the development of optimal primary tumor-specific CTL to the P815 mastocytoma, the EL4 thymoma, and the Lewis lung carcinoma is dependent on tumor Ags, on enhancement of T cell costimulation by B7.1, and on exogenous T helper activity in the form of IL-2 and IL-4. A relatively low concentration of IL-2 and IL-4 was required to limit the induction of lymphokine-activated killer cells. In the case of P815, the CTL were directed toward molecularly defined tumor rejection Ags. These primary cultures yielded long term T cell lines that were heterogeneous in fine tumor Ag specificity and in cytokine production.
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PMID:Generation of primary tumor-specific CTL in vitro to immunogenic and poorly immunogenic mouse tumors. 855 87

Repetitive administration of low doses of tumor necrosis factor (TNF) results in a state of selective tolerance to some of its effects. We have demonstrated that tolerance does not impair the therapeutic efficacy of TNF against a syngeneic murine B16BL6 melanoma and allows a complete cure. Another study, performed with a distinct tumor model, came to apparently contradictory results. To clarify this, we investigated whether the outcome depended on the tumor type and on the inclusion of interferon-gamma (IFN gamma) in the treatment. Three syngeneic tumors of different histological origin, i.e., B16BL6 melanoma, Lewis lung carcinoma (LLC) and EL4 lymphoma, were compared in C57BL/6 mice. The anti-tumor efficacy of TNF against B16BL6 and EL4 was not impaired in tolerant mice, but the effect of TNF against LLC was slightly, though significantly, reduced. Inclusion of IFN gamma in the treatment regimen, however, abolished this difference and resulted in complete cure for all 3 tumor systems. As therapeutically optimal doses were lethal in normal mice, only tolerance allowed a long-term cure. We conclude that the influence of tolerance on the anti-tumor activity of TNF as a single agent depends on the tumor type; in combination therapy with IFN gamma, however, tolerance allowed us to dissociate lethal toxicity from anti-tumor activity, irrespective of the tumor type tested.
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PMID:Anti-tumor activity of tumor necrosis factor in combination with interferon-gamma is not affected by prior tolerization. 884 44

To develop an efficient antitumor immunotherapy, we have examined if dendritic cells (DCs) loaded with soluble antigens by electroporation present more antigens via the MHC (major histocompatibility complex) class I pathway, which mediate a cytotoxic T-cell response. DCs loaded with ovalbumin (OVA) by electroporation presented more MHC class I-restricted determinants compared with DCs pulsed with OVA. When electroporated DCs were pulsed with OVA for additional times, both MHC class I- and II-restricted presentation of OVA were increased compared with each single procedure, including electroporation or simple pulse. Immunization with DCs loaded with OVA by electroporation induced higher cytotoxicity of splenocytes to E.G7 cells, a clone of EL4 cells transfected with an OVA cDNA, than immunization with DCs pulsed with OVA. In the animal study, immunization with DCs loaded with OVA or tumor cell lysates by electroporation induced an effective antitumor immunity against tumor of E.G7 cells or Lewis lung carcinoma cells, respectively. In addition, immunization with DCs loaded with antigen by combination of electroporation and pulse, completely protected mice from tumor formation, and prolonged survival, in both tumor models. These results demonstrated that electroporation would be a useful way to enhance MHC class I-mediated antitumor immunity without functional deterioration, and that the combination of electroporation and pulse could be a simple and efficient antigen-loading method and consequently lead to induction of strong antitumor immunity.
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PMID:Dendritic cells loaded with exogenous antigen by electroporation can enhance MHC class I-mediated antitumor immunity. 1468 78


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