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 partially characterized the T-cell subsets that control the growth of the C57BL/6 Lewis lung carcinoma 3LL transplanted into syngeneic mice. By analyzing the phenotypes of anti-tumor lymphocytes generated in vitro and in vivo, we have characterized a CD8 T-cell receptor (TcR) V beta 5,6 positive subpopulation of cytotoxic effectors important in retarding the growth of the transplanted tumor. In contrast, the rejection of 3LL appears to be hindered by the presence of a CD4 V beta II-positive subset since depletion of these lymphocytes in vivo with the appropriate monoclonal antibodies (MAbs) results in significant retardation of tumor growth. These results suggest that the cumulative positive and negative effects of distinct T-cell sub-populations determine the outcome of tumor progression and metastasis.
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PMID:T-cell subset analysis of 3LL tumor growth. 182 21

A 186Re-labeled monoclonal antibody (MAb), NR-LU-10, was used for the radioimmunotherapy of a subcutaneous human small cell lung carcinoma xenograft, SHT-1, in nude mice. Biodistribution with specific and irrelevant labeled MAb demonstrated peak tumor uptake of 8% and 3% of the injected dose/g at 2 days, respectively. Dosimetry analysis predicted tumor:whole-body radiation-absorbed dose ratios of 2.43:1 for NR-LU-10 and 0.62:1 for irrelevant MAb. Single-dose toxicity screening estimated a 50% lethal dose within 30 days of 600 microCi (880 cGy of whole-body radiation). As anticipated, a multiple-dose regimen of 490 microCi in four doses over 10 days (720 cGy of whole-body radiation, eight of eight surviving greater than 30 days) was less toxic than a single bolus dose of 430 microCi (644 cGy of whole-body radiation), six of eight surviving greater than 30 days). A multidose radioimmunotherapy regimen was initiated in nude mice bearing 66-mm3 tumors (total dose, 500 to 600 microCi). Complete remissions (greater than 140 days) were achieved in three of 16 mice, and the remainder showed a mean tumor growth delay of 53 days. Matched doses with irrelevant MAb produced one remission, one treatment-related death, and a mean growth delay of only 20 days in six of eight mice. Thus, in this nonoptimal radioimmunotherapy model, significant antitumor responses were observed using a mildly toxic multiple dosing regimen.
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PMID:186Re radioimmunotherapy of small cell lung carcinoma xenografts in nude mice. 184 57

Attempts to correct tumor hypoxia with oxygen-carrying solutions have used high concentrations of inspired oxygen (FiO2 100% or 95%). In the clinic, however, obtaining such high levels of FiO2 using mask ventilation in older patients or in children may be difficult. Since lower levels of FiO2 had not been previously tested, we examined the antitumor efficacy of FiO2 levels of 65, 85, and 95% breathed for 1 hr prior to and during irradiation used with the concentrated perfluorochemical emulsion F44E, the less concentrated emulsion, Fluosol-DA, or a new preparation consisting of purified bovine hemoglobin solution, PBHS. When tested in mice bearing the Lewis lung carcinoma with 2, 3, or 4 Gy daily for 5 days, daily Fluosol-DA produced only a small increase in the slope of the tumor growth delay versus irradiation alone, when used with 85% FiO2 (dose modifying factor [DMF] 1.3), but produced a DMF of 2.1 with 95% FiO2. Various concentrations of F44E (2, 4, or 8 g PFC/kg) each required a 95% FiO2 for full effect but the 8 g/kg dose had a discernable effect with an FiO2 of 65% and 85% (DMF 1.25 and 1.30, respectively). For PBHS, in contrast, a DMF of 1.6 was observed at 20% FiO2, but surprisingly this increased further to 2.1 with 95% FiO2. Further investigations of PBHS with irradiation demonstrated that daily administration of PBHS (12 ml/kg) 1 hr before single Xray fractions of 5, 10, 15, or 20 Gy with 20% FiO2 resulted in a DMF of 1.6-1.7 in the FSaIIC fibrosarcoma compared with irradiation alone when ascertained by tumor cell excision assay. These results indicate that to achieve maximum antitumor benefit with these oxygen-carrying solutions with radiation therapy, care must be taken to insure that FiO2 levels near 100% are achieved.
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PMID:Effect of oxygen level on the enhancement of tumor response to radiation by perfluorochemical emulsions or a bovine hemoglobin preparation. 191 27

The effects of expermentally induced hyper- and hypothyroidism on the growth and development of spontaneous pulmonary metastases of Lewis lung carcinoma (3LL) cells were studied in a murine system. Progression of 3LL tumors growing in mice was associated with significant reduction in the serum levels of T3 and T4. Subcutaneous (s. c.) injections (3 times/week) of T3 resulted in a hyperthyroid state with elevated T3 and reduced T4, whereas treatment with T4 induced a hyperthyroid state with elevated T3 and T4 levels. On the other hand, treatment with methimazole induced hypothyroidism with reduced T3 and T4 levels. Under these experimental conditions, treatment with T3 significantly inhibited spontaneous pulmonary metastases, and prolonged survivals of the mice. Methimazole suppressed primary and metastatic tumor growth and prolonged survival. In contrast, treatment with T4 enhanced primary tumor growth and development of pulmonary metastases of 3LL cells. Alveolar macrophages showed enhanced cytotoxicity against 3LL tumor cells after injections of thyroid hormones (T3 and T4) for 4 weeks. The NK activities of spleen cells of mice treated with T4 or methimazole were much lower than those of control mice, and were not affected by treatment with T3. These results imply that changes in thyroid functions may have important influence on natural host defenses against primary and metastatic lung cancer in humans.
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PMID:Effects of experimental hyper- and hypothyroidism on natural defense activities against Lewis lung carcinoma and its spontaneous pulmonary metastases in C57BL/6 mice. 194 98

Eighty-eight primary and secondary lung tumor specimens were subcutaneously transplanted into athymic nude mice. One third of all carcinoma specimens yielded tumor growth. Success rates were highest if fresh tumor pieces or fresh or frozen cell suspensions were implanted or injected. More than half of squamous cell and adenocarcinoma xenografts showed a lower degree of differentiation than the original tumor. The degree of dedifferentiation led to the diagnosis of large cell carcinoma by light microscopical criteria in 4 of these cases. All small cell carcinoma xenografts showed intermediate-cell type morphology irrespective of the cell type of the original tumor, and all large cell carcinoma xenografts showed features similar to the original tumor. Tumor latent periods were approximately twice as long during the first nude mouse passage than subsequent passages, and tumor doubling times remained stable during serial passages. We conclude that the large cell lung carcinoma subtype is a mixed bag of tumors and includes highly undifferentiated squamous cell and adenocarcinomas, that the small cell carcinomas remain in that histologic subtype during xenotransplantation, and that lung carcinoma xenografts display stable morphologic and kinetic features during serial xenotransplantation. Nude mouse xenografts may serve an in vivo model to study the biologic relationship of non-small cell lung carcinomas.
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PMID:Nude mouse xenografts as in vivo models for lung carcinomas. 196 90

The spontaneous tumoricidal abilities of alveolar and peritoneal macrophages from C57B1/6 mice bearing a metastatic or a nonmetastatic cloned variant of Lewis lung carcinoma (LLC) were measured. Cytotoxicity by alveolar macrophages was enhanced during the first few weeks after subcutaneous (s.c.) or intravenous (i.v.) injection of metastatic LLC-C3 cells, but not after injection of nonmetastatic LLC-C8 cells. Alveolar macrophages from mice with s.c.-injected metastatic tumors, but not with nonmetastatic tumors, could be further activated in vitro, but not beyond the maximal level of spontaneous cytotoxicity. Late in tumor growth, the spontaneous cytotoxicity by alveolar macrophages of metastatic LLC-C3 tumor bearers was suppressed and could not be increased by in vitro activation. The tumoricidal abilities of peritoneal macrophages from mice bearing either LLC-C3 or LLC-C8 tumors were modulated in a similar way, as were alveolar macrophages. The reduced cytotoxicity by alveolar macrophages from mice with nonmetastatic tumors or from mice bearing large metastatic tumors was not due to suppression by macrophage-derived prostaglandins. The loss of tumoricidal capabilities by macrophages from mice with large metastatic LLC-C3 tumors was not caused by elevated systemic prostaglandin E2 (PGE2) levels. These results suggest that alveolar and peritoneal macrophages are activated to be cytotoxic during development of pulmonary metastases and do not need to be functionally depressed for successful establishment of metastases.
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PMID:Tumoricidal activity of alveolar and peritoneal macrophages of C57BL/6 mice bearing metastatic or nonmetastatic variants of Lewis lung carcinoma. 198 86

Cocrynebacterium parvum (CP) was injected around the tumor and tumor cells were inoculated subcutaneously with activated peritoneal macrophages. The effects on the growth and metastases of Lewis lung carcinoma in C57BL/6 mice were observed. Experimental results indicated that CP had significant inhibitory effect on the tumor growth and lung metastases. The cytotoxic effects of activated peritoneal macrophages in mice on target tumor cells (L5178Y) in vitro were studied with the technique of 3H-TdR assay. The proliferation of tumor cells was markedly inhibited by the activated peritoneal macrophages of CP. Experiments showed that the antitumor mechanism of CP was the mediation via activated cytotoxic macrophages. These results indicated that CP is an effective immunostimulant. These findings will provide a scientific basis for the clinical treatment of the primary and metastatic lung carcinoma.
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PMID:[Inhibition of growth and metastases of lung carcinoma in C57BL/6 mice by Corynebacterium parvum and its antitumor mechanism]. 209 73

The combination of inhibitors of ornithine decarboxylase and polyamine oxidase and of antibiotics suitable for the (partial) decontamination of the gastrointestinal tract with a polyamine-deficient diet reduced the growth rate of Lewis lung carcinoma by more than 80%. The formation of lung metastases was prevented by 70 to 100%, depending on the treatment. The reduction of tumor growth was accompanied by a decrease of tissue polyamine concentrations, a reduced rate of tumor cell proliferation, and protein synthesis. The comparison of the ornithine decarboxylase inhibitors Eflornithine [D,L-2-(difluoromethyl)ornithine] and (E)-2-(fluoromethyl)dehydroornithine ethylester confirmed the greater in vivo potency of the latter compound. Our method of growth inhibition by systematic polyamine deprivation is not tumor specific, but presumably generally applicable to rapid growth.
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PMID:Endogenous and exogenous polyamines in support of tumor growth. 211 24

Histological sections of formalin-fixed, paraffin-embedded tissue comprising 60 surgical specimens of human lung carcinoma were Feulgen stained. The histomorphological images were transferred to an automated image analysing system (VISIAC) and analysed as follows. The geometrical centers of tumor cell nuclei were defined as vertices, and the minimum spanning tree (MST) was calculated based on the two-dimensional distance between the vertices. Segmentation of the images was performed semiautomatically by interactive definition of nuclei of interest and automated detection of nuclear boundaries. Several morphometric features of tumor cell nuclei were measured including size, DNA-content (extinction), and form factor, and were set in relation to parameters of the MST. The following results were obtained: DNA-content and tumor cell nucleus size ('center cell') of different microscopic tumor growth patterns are related to the number of nearest neighboring cells. No relation was found in the neighboring (surrounding) cells. The different cell types of lung carcinoma, i.e., the different microscopic tumor textures expressed the relation of center cell features to the parameters of MST. A high amount of DNA content in branching points of the MST for epidermoid carcinoma may be interpreted as carcinoma growing in epidermoid textures tend to proliferate from tumor cell nuclei related to at least one neighboring cell. The opposite was found for large cell anaplastic carcinoma (no perceptible microscopic textures of the tumors) which showed the highest DNA content in tumor cell nuclei but which was not related to any neighboring cells. This technique allows analysis of growth centers and microenvironment conditions in human lung cancer in relation to tumor texture at the light microscopy level.
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PMID:Combined morphometrical and syntactic structure analysis as tools for histomorphological insight into human lung carcinoma growth. 217 50

HO-221, N-[4-(5-Bromo-2-pyrimidinyloxy)-3-chlorophenyl]-N'-(2-nitrobenzoyl ) urea is a novel benzoylphenylurea derivative. We had interested in various pharmacological actions of benzoylphenylurea compounds. Therefore, many compounds were synthetized and tested in various screening systems. In the process with these tests, we found HO-221 which showed an excellent antitumor activity. The antitumor activity of HO-221 was judged from the survival time and the tumor weight of experimented tumor-bearing animals. HO-221 preparation was orally administered. The compound exhibited significant effects against various animal tumors (P388, L1210, M5076, LLC, C38, S180, W256), and especially effective against the solid tumors. HO-221 was also markedly effective to MX-1 and LX-1 implanted into nude mice. However, the effect against mouse B16 melanoma was moderate. In addition, HO-221 showed a schedule dependency and once every 4 or 7 days treatments were most effective. The antitumor activities of the compound against advanced L1210 and Lewis lung tumors were examined. Tegafur and ara-C were used as reference drug for the study. Three agents showed the antitumor activities against L1210. Against Lewis lung carcinoma, HO-221 showed both the increase of life span and the tumor growth inhibition. On the other hand, tegafur and ara-C were ineffective for the increase of life span.
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PMID:[Antitumor effect of a benzoylphenylurea derivative HO-221]. 226 Aug 71


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