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Query: UMLS:C0684249 (lung carcinoma)
 23,830 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The importance of different lymphocyte cell populations in early recognition and destruction of tumor cells has not been fully established. Certainly natural killer cells and cytotoxic T lymphocytes are involved. Using a recently developed monoclonal antibody (GK 1.5) that has been shown to have in vivo cytotoxic activity directed at L3T4-bearing T cells, we provide in these experiments evidence that T-helper cells are also important in early antitumor immunity. Development of progressive tumor growth after the subcutaneous inoculation of 10(5) Lewis lung carcinoma (3LL) cells was greater in antibody-treated mice (13 of 20 treated mice vs. 6 of 21 controls). Nevertheless, in those animals that developed tumors, the latentcy period (time from tumor cell inoculation until tumor first palpable) and tumor growth rate were no different in antibody-treated mice when compared with control animals. In subsequent experiments, animals were exposed to irradiated tumor cells in Freund's adjuvant on three occasions and tumor growth was then assessed. Growth was slower in the sensitized group. Administration of GK 1.5, however, did not enhance the tumor growth rates in either the previously sensitized or control groups. The results suggest that T-helper cells might be of greater functional importance in early tumor cell recognition and destruction and of lesser importance in the restraint of tumor growth, once the tumor has become established.
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PMID:Increased susceptibility to inoculated Lewis lung carcinoma (3LL) but unaltered tumor growth in mice treated with monoclonal antibody to L3T4 on mouse T-helper cells. 257 72

This study was undertaken to determine whether in vitro treatment of Lewis lung carcinoma (3LL) cells with ultraviolet (UV) radiation could increase their immunogenicity. Tumor cells were irradiated with UV light from a germicidal lamp (254 nm; UV-C) at a dose of 720 J/sq m. After 2 weeks of culture, the surviving cell population was cloned by limiting dilution. Cell suspensions of each clone were injected intrafootpad in C57BL/6 mice at a dose of 2.5 X 10(5) cells per mouse. Eighty independent clones were tested. Fifty-one clones showed decreased tumorigenicity and failed to grow in 20 to 95% of immunocompetent mice, whereas they produced tumors in 100% of irradiated (550 R) and athymic nude mice. These clones were designated "tum-" (nontumorigenic) clones. In contrast, all 25 clones selected from the untreated parental 3LL induced progressively growing tumors in 100% of the mice. After two courses of UV treatment, the uncloned 3LL population was rejected in 45% of inoculated mice. Mice rejecting an inoculum of a tum- clone were completely resistant to subsequent challenge with higher doses of the same or unrelated tum- clones. This resistance was fully expressed even after irradiation of immune mice with 550 R. Mice immune to a tum- clone also were able to prevent the growth of various tum+ clones or untreated 3LL tumor cells. When tum- and tum+ clone cells were simultaneously inoculated intrafootpad in opposite legs, rejection of tum- clone resulted also in the prevention of the growth of tum+ clone. Spleen cells of immune mice caused rapid elimination of radiolabeled 3LL tumor cells from the place of their inoculation (intrafootpad) and prevented tumor growth. In an in vitro cytotoxic assay, spleen cells after in vivo and in vitro immunization with tum- clones demonstrated high cytotoxic activity against various tum+ clones and parental 3LL cells, as well as against tum- clones. In addition, parental 3LL tumor cells and tum- cells were similarly able to inhibit cytotoxic activity in the cold target inhibition assay. However, in contrast to tum- cells, 3LL cells were less efficient in in vitro restimulation of cytotoxic activity of immune spleen cells. Therefore, these data suggest that tum-, tum+, and parental 3LL cells share a common antigenic specificity, which is not immunogenic in 3LL cells. UV treatment presumably converted the antigenic determinants present in the 3LL cells into an immunogenic form.
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PMID:Induction of highly immunogenic variants of Lewis lung carcinoma tumor by ultraviolet irradiation. 258 Jun 24

Limax is a mollusk with lung, the whole body of which has manifested medicinal values. It can be taken orally and used externally. The experimental studies on the antitumor effect of Limax on NIH mice bearing ARS (ascites type) or Lewis lung carcinoma were carried out by using tumor inhibitory rate, tumor mean diameter doubling time, tumor growth delay time or the host existence time as the experimental indexes. The initial results indicated that the mixed suspension liquid of Limax had an obviously inhibitory effect upon the above mentioned experiment tumors.
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PMID:[Antitumor effect of Limax in tumor-bearing mice]. 261 58

New reactions of methyl 2,2-difluoro glycosides are described that were utilized for synthesis of some novel nucleoside derivatives. Thus, treatment of methyl 2-deoxy-2,2-difluoro-3,4-O-isopropylidene-alpha (beta)-D-erythro-pyranoside (2) with anhydrous HCl resulted in selective displacement of one fluorine atom with chlorine to give a 2-deoxy-2-chloro-2-fluoro glycoside 3. Reaction of 3 with silylated uracil in the presence of SnCl4 provided a 2-deoxy-2-fluoro-2-uracil-substituted glycoside 4. 2-Fluoro-2-deoxy glycosides substituted with other pyrimidines at C-2 were prepared similarly by the reaction of acylated 2,2-difluoro or 2-fluoro-2-bromo derivatives (5 and 6, respectively) with silylated pyrimidines. The resulting 2'-fluorinated isonucleosides were evaluated for their antitumor and antiviral activities. Compounds 7a,b, 8a,b, and 10a,b demonstrated 50% tumor cell growth inhibition in vitro (IC50) at 10(-4)-10(-5) M. At similar concentrations no antiviral activity was observed in vitro. Therapeutic activity was obtained with 7a,b and 8a,b in DBA/2 mice with L1210 leukemia. Administration of 7a,b at 500 mg/kg, ip daily, for 5 consecutive days, resulted in a 55% increase in life span (% ILS) while administration of 8a,b in the same manner at 200 mg/kg caused a 29% ILS. Treatment with 7a,b to mice with drug-resistant L1210 sublines (5-FU and araC) resulted in 22 and 57% increases in life span, respectively. Lewis lung carcinoma and M5076 sarcoma in mice also responded to the administration of 7a,b with reductions in tumor growth for both tumors and significant increases in life span in mice with Lewis lung carcinoma. Although the mechanism of action of 7a,b is not known, it has been found to be a relatively fast-acting, cell-cycle nonspecific cytotoxic agent that decreases [3H]deoxyuridine incorporation, blocks L1210 cells at the G2 phase of the cell cycle, and is not reversed by exogenous thymidine. These 2'-fluorinated isonucleosides have demonstrated biological activity and may have potential as antitumor drugs.
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PMID:2'-Fluorinated isonucleosides. 1. Synthesis and biological activity of some methyl 2'-deoxy-2'-fluoro-2'-pyrimidinyl-D-arabinopyranosides. 270 26

We have examined the effects of a wide range of levels of Therox, a perfluorochemical emulsion containing bis-perfluorobutyl ethylene (F44E) with carbogen breathing on the tumor growth delay of the Lewis lung carcinoma produced by single dose radiation and fractionated radiation. The enhancement in tumor growth delay with single dose radiation therapy increased as the dose of F44E was increased from 1.2 g/kg (0.03 ml) to 4 g/kg (0.1 ml). As the dose was increased further from 6 g/kg (0.15 ml) to 8 g/kg (0.2 ml) and then to 12 g/kg (0.3 ml), there was a progressive decrease in the tumor growth delay observed. The dose of 4 g/kg was the optimal F44E level with single dose radiation therapy, giving a dose modifying factor of 2.4 +/- 0.2. This was true whether administered as a 48% (v/v) emulsion in 0.1 ml or as a 16% (v/v) emulsion in 0.3 ml. When the injection volume was varied from 0.1 ml to 0.4 ml at the 4 g/kg or 6 g/kg dose, thereby varying the emulsion concentration from 48% (v/v) to 12% (v/v) or 18% (v/v), the results tended to indicate that the volume of injection may be more important than the emulsion concentration, i.e., an injection volume of 0.2 ml produced the greatest tumor growth delay for both doses, and the emulsion concentration of 0.2 ml and 4 g/kg of F44E is 24% (v/v) whereas the emulsion concentration of 0.2 ml and 6 g/kg of F44E is 36% (v/v). Administering any dose of the emulsion with carbogen for 1 h prior to and during the radiation fraction on Day 1 only of a daily fractionated radiation protocol (3 Gy/fraction x 5 days) had very little effect on tumor growth delay compared to radiation and daily carbogen breathing. When F44E was administered on treatment Days 1, 3, and 5 with carbogen breathing, there was an increased effect on tumor growth delay which reached a maximum at 4 g/kg (0.1 ml) of 10.0 +/- 1.2 days compared with 6.7 +/- 1.0 days for radiation with daily carbogen breathing. However, when the F44E emulsion was administered every day with fractionated radiation and carbogen breathing, there was a marked enhancement in tumor growth delay observed across the entire dosage range, from 1.2 g/kg to 12 g/kg.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Optimization of perfluorochemical levels with radiation therapy in mice. 271 54

L6 is a murine monoclonal antibody (MAb) binding to cells of most human carcinomas, mediating antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity, and inhibiting tumor growth in nude mice [10]. Fab and F(ab')2 fragments of L6, as well as intact MAb, have been evaluated for immunospecific localization in nude mice xenografted with a human lung carcinoma. They were compared with preparations of an isotype-matched control immunoglobulin, P1.17, after labelling with 125I or 131I. L6 Fab fragments prepared from MAb L6 and labelled with 67Ga via desferrioxamine were also tested. The data suggest that MAb L6 may be useful for in vivo detection of human carcinomas.
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PMID:Evaluation of L6, an anti-carcinoma murine monoclonal antibody, in tumor-bearing nude mice. 277 57

5-fluoro-3,4-dihydro-2,4-dioxo-N-[2-2- (dimethylphenylsilyl)ethylthioethyl]-1(2H)-pyrimidinocarb oxamide (SDK-12B-5), a novel antitumor agent, is covalently linked with 5-fluorouracil (5-FU) and 2-[(2-dimethylphenylsilyl)ethylthio] ethylamine(SDK-103) which possesses itself antitumor activity against murine solid tumors. It has a broad antitumor spectrum in experimental tumor systems including murine leukemias. Furthermore, SDK-12B-5 administered p.o. with various treatment schedules inhibited significantly the tumor growth of human breast cancer (MX-1), colon cancer (Co-4) and lung cancer (LX-1 and OAT) cells in BALB/c nu/nu mice and the chemotherapeutic index was about 10 for 4 different human cancer xenografts. In the Lewis lung carcinoma (LLC) metastasis model, SDK-12B-5 in combination with amputation of tumors inhibited significantly both the lymph node metastases and lung metastases of LLC and prolonged the life span (%ILS:91%) of BDF1 mice. We also found that the cell killing effect of SDK-12B-5 was affected by both concentration and exposure time in cultured human lung cancer (OAT) cells using soft-agar colony assay. A significant augmentation of delayed type hypersensitivity (DTH) response induced by SDK-12B-5 in comparison with the mixture of SDK-103 and 5-FU was seen when it was administered p.o. simultaneously with the immunization of sheep red blood cell (SRBC) in retired CD1 mice. From the studies on tissue distribution and pharmaco-kinetics of SDK-12B-5 by HPLC and ICP analysis. the persistence of SDK-12B-5 levels in serum and tumors was correlated with the findings that a maximum chemotherapeutic effect was obtained when SDK-12B-5 was administered p.o. repeatedly with every other day to avoid the cumulative toxicity.
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PMID:[Antitumor effects of 5-fluorouracil-bound organic silicon compound]. 278 16

Clinically, 5-formyltetrahydrofolate (leucovorin, folinic acid, LV) in combination with 5-fluorouracil (5-FU) has been used at various doses, schedules, and routes of administration with therapeutic benefit to patients with advanced colorectal carcinoma and breast carcinoma. Clinical experiences have been primarily with LV doses of 25, 200, and 500 mg/m2 administered by either short-term intravenous infusion, daily continuous infusion, or orally. In patients with lung carcinoma, oral administration of dl-LV at 125 mg/m2 hourly for 4 hours (total dose of 500 mg/m2) gave the following peak plasma folate concentrations: dl-LV, 4.6 + 1.9 microM; 5-methyltetrahydrofolate, 4.3 + 2.1 microM; and no detectable l-LV in most cases. The d-LV/5-methyltetrahydrofolate ratios, however, were lower for the oral route than for the same dl-LV dose administered by 2-hour intravenous infusion in the same patient. To determine if there is a relationship between the dose, schedule, or route of administration and the therapeutic efficacy of LV combined with 5-FU, studies were carried out in rats with transplantable colon carcinoma. 5-Formyltetrahydrofolate was administered at various doses by either 2-hour infusion, 2-day continuous intravenous infusion, or by divided hourly oral doses for 4 hours. In all cases, the total doses of dl-LV administered were 100, 200, and 400 mg/kg. Data obtained to date indicate: (1) plasma folate concentrations by intravenous administration were dose dependent, but lower and saturable concentrations of folates were observed by oral administration; and (2) while the concentrations of 5-methyltetrahydrofolate achieved by the 2-hour infusion schedule were relatively constant and independent of the dose of dl-LV administered, conversion of dl-LV to 5-methyltetrahydrofolate with the 2-day infusion of 100, 200, and 400 mg/kg was dose dependent. In humans, however, conversion was independent of the route of administration of dl-LV (19% for the 2-hour infusion and 23% for the 5-day infusion of 500 mg/m2 dose). Preliminary results for antitumor activity of 5-FU in combination with dl-LV, administered by either 2-hour intravenous infusion (400 mg/kg/day for 5 days) or orally (100 mg/kg/hour for 4 hours), yielded similar inhibition of in vivo tumor growth, each being greater than what was achieved with 5-FU alone.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Toxicity and antitumor activity of 5-fluorouracil in combination with leucovorin. Role of dose schedule and route of administration of leucovorin. 278 77

Perfluorochemical emulsion can dissolve large amount of oxygen, carry it into tissues, and consequently enhance the response of hypoxic tumor cells to radiation. Previously we reported on the radiosensitizing effect of perfluorochemical emulsion. In the present study, the minimal effective dose of Fluosol-DA Saline 20% (FDAS), one of preparations of perfluorochemical emulsion, was determined. Mice bearing Lewis lung carcinoma in their thighs were injected in single i.v. of FDAS (1.25-20 ml/kg) and were allowed to breath carbogen (95% O2 + 5% CO2) for 30 min. before and during irradiation (15 Gy). The effect of FDAS was measured by the growth delay of the treated tumor. Administration of FDAS at over 5 ml/kg together with carbogen breathing significantly (p less than 0.01) enhanced the tumor growth delay as compared with treatment of carbogen breathing without FDAS. There was a significant difference (p less than 0.05) in the radiosensitizing effect between injection of FDAS at 5 ml/kg and 20 ml/kg, while there were not significant differences between injection of FDAS at 5 ml/kg and 10 ml/kg, or 10 ml/kg and 20 ml/kg, respectively. These results indicate that the minimal effective dose of FDAS is 5 ml/kg, which could be applied to clinical fractionated irradiation therapy as a standard FDAS-dose.
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PMID:[Minimal effective dose of perfluorochemical emulsion as a radiosensitizer]. 279 48

The influence of combination of local hyperthermia and radiation on tumor growth and metastases was studied using Lewis lung carcinoma. Tumors growing intramuscularly in the right hind legs of C57BL/6 mice were irradiated at 10 Gy of radiation dose and immersed in a water bath. Time and number of development of metastases were determined according to size and number of lung colonies at 19 days after tumor implantation. Local hyperthermia at 42.8, 43.3 or 43.5 degrees C for 30 min immediately after or before irradiation enhanced the growth delay of tumor with irradiation or with hyperthermia alone. Development of metastases several days after heating was also inhibited by the combination of heating and irradiation. These effects were diminished with hyperthermia applied 3 hr or more after irradiation. Promotion of metastases around the time of heating by severe hyperthermia with above 43.3 degrees C alone was not inhibited by combination with radiation, regardless of their sequence. Radiation had no effect on the number of metastases developed by the heating. However, irradiation 48 hr or more before severe heating reduced the number of metastases developed by the heating.
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PMID:[Influence of local hyperthermia combined with radiation on tumor growth and lung metastases of transplantable Lewis lung carcinoma growing in hind legs]. 279 49


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