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)

Through the extensive investigation of new mitomycin C (MMC) derivatives, several compounds with disulfide at N-7 were found to show activities superior to MMC against murine Sarcoma 180 solid tumor. Among them, 7-N-[[2-[[2-(gamma-L-glutamylamino)ethyl]dithio]ethyl]]- mitomycin C (KW-2149) was selected for further evaluation of antitumor activity and toxicity in mice. KW-2149 exhibited activity superior to MMC in increasing survival of i.p. inoculated P388 leukemia-, M5076 sarcoma-, and B16 melanoma-bearing mice. KW-2149 administered i.v. also exhibited superior activity in inhibiting the growth of s.c. inoculated P388 leukemia, M5076 sarcoma, and colon 26 adenocarcinoma and in increasing survival of i.v. inoculated P388 leukemia- and M5076 sarcoma-bearing mice. Furthermore, KW-2149 remarkably increased the life span of MMC-resistant P388 leukemia- and L1210 leukemia-bearing mice. KW-2149 and MMC inhibited the growth of human tumors inoculated into nude mice. The activity of KW-2149 was prominent in human lung carcinoma Lu-65 and Lu-99, bladder carcinoma T24, and epidermoid carcinoma A431. KW-2149 was comparable to MMC in decreasing the number of WBC in the peripheral blood, and the thrombopenia induced by KW-2149 was mild and recovery was rapid. The in vitro anticellular spectrum of KW-2149 against 23 human tumor cell lines was similar to that of MMC. However, KW-2149 inhibited the growth of the cell lines at concentrations of 10- to 100-fold lower than MMC and showed efficient cytotoxicity against MMC-insensitive tumor cell lines. These included lung epidermoid carcinoma Calu-1, stomach carcinoma MKN-28, colon adenocarcinoma DLD-1, colon adenocarcinoma LoVo, bladder carcinoma HT-1197, sarcoma G-292, and melanoma SK-MEL-28 cells. These results indicate that KW-2149 bears interesting characteristics as a new anticancer drug and warrants further development.
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PMID:Antitumor activity of 7-N-[[2-[[2-(gamma-L-glutamylamino)ethyl]dithio]ethyl]]-mitomycin C. 198 76

S 12363 is a new Vinca alkaloid derivative obtained by appending an optically active alpha-aminophosphonate at the C23 position of O4-deacetyl vinblastine. S 12363 was evaluated for cytotoxic and antitumor activity against a spectrum of murine and human tumors. This compound was, respectively, on average, 72- and 36-fold more cytotoxic than were vincristine and vinblastine, when tested on a panel of 2 murine and 37 human tumor cell lines using the microculture tetrazolium assay. S 12363 exhibited significant antitumor activity against murine transplantable tumors (i.p. and s.c. P388 leukemia, i.p. L1210 leukemia, i.p. and i.v. B16 melanoma, i.p. M5076 sarcoma, and s.c. colon adenocarcinoma 38), while no activity was observed on s.c. Lewis lung carcinoma. S 12363, when administered i.p., showed moderate activity on human NCI-H460 lung and PANC-1 pancreas tumor xenografts in nude mice. However, when it was administered i.v., it exerted a significant activity against human HT-29 colon, NCI-H460 lung, NCI-H125 lung, PANC-1 pancreas, and A-431 vulvar tumor xenografts. S 12363 was also active in vivo against a P388 leukemia subline resistant to vincristine. On the in vivo panel of tumors used in this study, S 12363 was at least as active as reference compounds, while its optimal dosage was 10- to 40-fold lower than that of vinblastine, depending on the models studied. The effects of schedule and route of administration on the antitumor activity of S 12363 were studied in both i.p. inoculated P388 leukemia and B16 melanoma, in which the activity was improved by single and intermittent treatment (Days 1, 8, and 15) and i.p. route. S 12363, which differs only by the configuration of the asymmetric carbon atom of the side chain, was 300-fold less cytotoxic and 1000-fold less potent in vivo than was S 12363. These results suggest that S 12363 could present a therapeutic advantage over its congeners and deserves further pharmacological evaluations.
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PMID:Preclinical antitumor activity of a new Vinca alkaloid derivative, S 12363. 201 95

Between May 1986 and August 1989, we treated 18 patients with 21 recurrent or persistent brain metastases with stereotactic radiosurgery using a modified linear accelerator. To be eligible for radiosurgery, patients had to have a performance status of greater than or equal to 70% and have no evidence of (or stable) systemic disease. All but one patient had received prior radiotherapy, and were treated with stereotactic radiosurgery at the time of recurrence. Polar lesions were treated only if the patient had undergone and failed previous complete surgical resection (10 patients). Single doses of radiation (900 to 2,500 cGy) were delivered to limited volumes (less than 27 cm3) using a modified 6MV linear accelerator. The most common histology of the metastatic lesion was carcinoma of the lung (seven patients), followed by carcinoma of the breast (four patients), and melanoma (four patients). With median follow-up of 9 months (range, 1 to 39), all tumors have been controlled in the radiosurgery field. Two patients failed in the immediate margin of the treated volume and were subsequently treated with surgery and implantation of 125I to control the disease. Radiographic response was dramatic and rapid in the patients with adenocarcinoma, while slight reduction and stabilization occurred in those patients with melanoma, renal cell carcinoma, and sarcoma. The majority of patients improved neurologically following treatment, and were able to be withdrawn from corticosteroid therapy. Complications were limited and transient in nature and no cases of symptomatic radiation necrosis occurred in any patient despite previous exposure to radiotherapy. Stereotactic radiosurgery is an effective and relatively safe treatment for recurrent solitary metastases and is an appealing technique for the initial management of deep-seated lesions as a boost to whole brain radiotherapy.
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PMID:The treatment of recurrent brain metastases with stereotactic radiosurgery. 217 75

The antimetastatic activity of adriamycin in combination with proteinase inhibitors was investigated in mice bearing the metastatic tumors L1210 leukemia, Lewis lung carcinoma or M5076 sarcoma. Leupeptin, a cathepsin B inhibitor, when administered as a single agent was devoid of antimetastatic activity but some therapeutic activity was noted in mice with Lewis lung carcinoma when the agent was administered in combination with adriamycin. Pepstatin A, a cathepsin D inhibitor, had no effect as a single agent in mice with L1210 leukemia but displayed some antimetastatic activity in mice with Lewis lung carcinoma. In mice with M5076 sarcoma the combination of pepstatin A and adriamycin resulted in antimetastatic activity significantly greater than that observed with each agent alone. These results suggest that combinations of proteinase inhibitors with antitumor drugs such as adriamycin, might result in more effective antimetastatic treatment.
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PMID:Antimetastatic activity of adriamycin in combinations with proteinase inhibitors in mice. 233 38

BMY-28175 is a novel antitumor antibiotic produced in fermentation by Actinomadura verrucosospora. The cytotoxic effects of BMY-28175 were determined using murine and human tumor cell lines in vitro. Following 72 hour exposure, the drug had IC50 values 1.5 to 13.5 ng/ml in a microtiter assay. BMY-28175 was evaluated for antitumor activity against several experimental murine and human tumor models. The drug administered ip was active against ip implanted P388 leukemia, L1210 leukemia, B16 melanoma, M109 lung carcinoma, C26 colon carcinoma, M5076 sarcoma and Lewis lung carcinoma. In addition, BMY-28175 administered iv was active against iv implanted P388 and L1210 leukemias. BMY-28175 was active against sc implanted B16 melanoma (increased lifespan and/or inhibition of primary tumor growth) in about 60% of the tests. The growth of sc implanted M109 was inhibited by BMY-28175 in a single experiment. BMY-28175 was also active against the MX-1 human mammary xenograft implanted in the subrenal capsule of nude mice. The optimal dose for BMY-28175 in these various studies ranged from 0.16 micrograms/kg per injection with consecutive daily (qd1-9) administration, to 51.2 micrograms/kg with single dose administration. The results of these studies indicate that BMY-28175 is one of the most potent antitumor agents yet observed, with a broad spectrum of activity against tumors of murine and human origin and activity against tumors located distal to the site of drug administration.
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PMID:Experimental antitumor activity of BMY-28175 a new fermentation derived antitumor agent. 234 72

Ten examples of giant cell carcinoma of the lung were examined by immunohistochemistry for expression of keratin and vimentin intermediate filaments and for epithelial membrane antigen (EMA). Six cases were also examined electron microscopically. Keratin expression and, to a lesser extent, EMA immunoreactivity were reduced in comparison with better differentiated forms of lung carcinoma. Vimentin expression was increased, often taking the form of strong paranuclear staining. This may correspond to dense paranuclear aggregates of intermediate filaments seen ultrastructurally. Desmosomes were absent or sparse in most tumours. We propose that giant cell carcinoma arises by a process of dedifferentiation. The resulting loss of epithelial features gives rise to neoplastic cells which have features in common with some forms of sarcoma.
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PMID:Giant cell carcinoma of the lung--immunohistochemical and ultrastructural evidence of dedifferentiation. 245 72

Clomesone was evaluated for antitumor activity against a spectrum of animal tumor models. Clomesone exhibited significant antitumor activity against the murine L1210 leukemia implanted i.p., s.c., and intracerebrally (i.c.). Activity against s.c.-implanted tumor was largely independent of schedule and route of administration. Therapeutically optimal single-dose treatment (for tumored mice) was less toxic to nontumored mice than therapeutically optimal prolonged treatment. Clomesone also exhibited activity against other murine tumors (P388 leukemia, B16 melanoma, Lewis lung carcinoma, and M5076 sarcoma). It was active against P388 leukemia sublines resistant to cyclophosphamide, L-phenylalanine mustard, and cis-diamminedichloroplatinum(II). No activity was observed against a P388 subline resistant to N,N'-bis(2-chloroethyl)-N-nitrosourea or against Ridgway osteogenic sarcoma, a nitrosourea-resistant murine solid tumor. Clomesone is generally as effective as the chloroethylnitrosoureas against experimental tumor models. Since clomesone does not have the hydroxyethylating and carbamoylating activities of the chloroethylnitrosoureas (which do not appear to contribute to antitumor activity), it would likely be a more toxicologically selective compound. It may prove to be less carcinogenic than the chloroethylnitrosoureas, and it may contribute less target organ toxicity and less interference with the actions of other drugs when used in combinations.
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PMID:Antitumor activity of 2-chloroethyl (methylsulfonyl)methanesulfonate (clomesone, NSC 33847) against selected tumor systems in mice. 253 44

RSU 1069 and RSU 1164 are electron affinic agents that contain a nitro group together with a weakly basic alkylating aziridine moiety, and they represent lead compounds in the development of dual-function, bioreductive, hypoxic cell radiosensitizers. We studied the pharmacokinetics of these drugs in mice carrying KHT sarcoma. Lewis lung carcinoma, and B16 melanoma. Following an i.p. dose of 80 mg/kg, absorption was rapid and the elimination t1/2 was in the region of 30 min for both agents. Maximal tumour levels were 91, 16 and 19 microgram/ml for RSU 1069 and 109, 26 and 28 microgram/ml for RSU 1164 in. the B16, KHT and Lewis lung tumours, respectively. In B16 melanoma these levels corresponded to tumour:plasma ratios of 3.8 for RSU 1069 and 3.7 for RSU 1164. Cellular uptake of RSU 1069, RSU 1164 and a related compound, RB 7040, was measured in vitro as a function of extracellular pH. Melanotic cells from both B16 melanoma and HX118, a human tumour xenograft, showed substantially greater accumulation of these weakly basic sensitizers than any other cell type examined. Ratios of intra-:extracellular concentration (Ci/Ce) for RSU 1069 were around unity and independent of pH for Lewis lung cells and HX34 amelanotic melanoma cells, whereas ratios of up to 3 and 5 were obtained in B16 and HX118 cells, respectively. The highest measured value of Ci/Ce was 15 for RSU 1164 in HX118 cells at pH 8.4; this compares with a ratio of 1.5 for HX34 cells at the same pH. These studies indicate that the high levels of uptake of the weakly basic sensitizers into melanotic melanoma in vivo is a cell-mediated phenomenon and may be due to a lower average intracellular pH in the melanotic cells.
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PMID:High uptake of RSU 1069 and its analogues melanotic melanomas. 254 36

We have experienced a case of S 100 protein positive large cell carcinoma of the lung which metastasized to the jejunum. The present case had a somewhat morphological resemblance to a Ki-1 lymphoma and/or an interdigitating cell sarcoma, and its differential diagnosis was problematic. This type of case, to our knowledge, is rare in the literature. The morphologic, immunohistologic, and electron microscopical findings of the neoplastic cells are described in this study.
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PMID:[A case of S 100 protein-positive large cell carcinoma--its pathological study]. 254 36

To investigate the characteristics in antitumor effects of 2-trimethylsilylethylthioethylamine(KAS-010) and its conjugate with 5-FU (KAS-011), the antitumor and immunomodulating activities of these silicon compounds were examined with various systems. Both KAS-010 and KAS-011 administered orally was found to be effective to B 16 melanoma, Meth A sarcoma and MM 46 mammary carcinoma in vivo. On the other hand, KAS-011 administered orally exhibited a marked antitumor activity against L 1210 leukemia bearing mice. Furthermore, these silicon compounds inhibited significantly metastases to the lymph nodes and lung of Lewis lung carcinoma implanted id into the right ear of BDF1 mice. Especially, KAS-011 in combination with tumor amputation resulted in a remarkable prolongation of the survival time (% ILS: 93.8%) in this antimetastatic model. The cell killing effect was mainly dependent on the exposure time of these silicon compounds in cultured KB and human lung cancer (OAT) cells. Moreover, a significant increase of delayed type hypersensitivity reaction (DTHR) to sheep red blood cell (SRBC) induced by KAS-010 was seen in old aged mice. The DTHR in B 16 melanoma and Ehrlich carcinoma bearing mice treated with KAS-010 was significantly higher than those of non-treated tumor bearing mice, indicating an enhanced cellular immunity to KAS-010 possibly resulting in a remarked antitumor effect. We also found that tumor free mice treated these silicon compounds were acquired specific tumor immunity to Meth A sarcoma and MM 46 mammary carcinoma.
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PMID:[Characteristics in antitumor effects of organic silicon related compounds]. 254 47


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