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)

TCNU (1-(2-chloroethyl)-3-[2-(dimethylaminosulphonyl)ethyl]-1-nitrosour ea) is a newly developed water-soluble nitrosourea based on the endogenous aminoethanesulphonic acid taurine. TCNU was in an extended phase I trial given orally every 4-8 weeks using a stepwise dose escalation from 20 to 170 mg/m2. One hundred and thirty-nine patients received a total of 323 courses. Minor haematologic toxicity was observed in 12 patients treated at dose levels less than 70 mg/m2. Thrombocytopenia WHO grades 1-4 occurred in 43% (55/127) and leucopenia WHO grades 1-3 in 45% (57/127) of the patients treated at dose levels greater than or equal to 70 mg/m2. Nausea and vomiting was recorded in about half the patients despite the use of metoclopramide. At the initial dose level 41 patients received greater than or equal to 3 courses of TCNU. Cumulative leucopenia and thrombocytopenia occurred in 3/41 and in 12/41 patients, respectively, while reversible hepatotoxicity was observed in two patients. Antitumour activity was observed in patients with advanced squamous cell, adeno- and large cell carcinoma of the lung. The recommended starting doses for phase II trials with TCNU are as follows: heavily pretreated patients 90 mg/m2, minimally/-moderately pretreated patients 110 mg/m2 and previously untreated patients 130 mg/m2 with TCNU given every 4-5 weeks, the repeated doses and intervals being adjusted to individual tolerance.
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PMID:A phase I clinical evaluation of 1-(2-chloroethyl)-3-[2-(dimethylaminosulphonyl)ethyl]-1-nitrosou rea (TCNU). 343 47

The T1 and T2 NMR relaxation times of water protons in plasma, obtained from patients with lung carcinoma, healthy volunteers, and patients with nontumor diseases were measured at a resonance frequency of 20 MHz. Additionally hematologic parameters were determined. In tumor patients the mean plasma T2 was shortened by about 20%, and an increase in the blood sedimentation rate (BSR) was noted. Similar but less pronounced results were found for the nontumor group of patients, indicating that the shortening of T2 in plasma is a secondary host response. However, a plot of plasma 1/T2 versus BSR from tumor patients showed a significant correlation between these two parameters. No such correlation could be detected in the nontumor group of patients. The correlation of 1/T2 with BSR, found solely in the tumor patient group, increased the diagnostic sensitivity of T2 measurements and may help to differentiate between malignant and nonmalignant disease. No significant variation in the T1 spin-lattice relaxation time was observed.
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PMID:NMR relaxation times T1 and T2 of water in plasma from patients with lung carcinoma: correlation of T2 with blood sedimentation rate. 343 14

The search for new water-soluble analogues of camptothecin (CPT) with higher activity and less toxicity has led to the development of a novel compound, 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxy-camptothecin (CPT-11), which showed significant antitumor activity against a broad spectrum of experimental tumor models by i.p., i.v., or oral administration. When its activity against L1210 was compared with that of CPT and known derivatives, CPT-11 was most effective, giving the highest maximum increase in life span (ILS) and showing good activity over a wide dose range. The antitumor activity of CPT-11 was shown against tumors not only in the ascites form but also in the solid form. Included among the more susceptible murine tumors are S180, Meth A fibrosarcoma, Lewis lung carcinoma, Ehrlich carcinoma, MH134 hepatoma, mammary carcinoma of C3H/HeN mice, L1210, and P388 leukemia. Probable cures of these tumors were induced frequently by CPT-11. The antitumor activity of CPT-11 against i.p.-implanted L1210 was superior to that of Adriamycin in maximum ILS, the number of cured mice, and the therapeutic ratio. CPT-11 at a dose of 100 mg/kg produced an ILS in excess of 300% with five of six mice surviving tumor free, and effected 100% tumor regression at 200 mg/kg, whereas the optimum dose of Adriamycin, 12.5-25 mg/kg, brought about 114-129% ILS with one of six mice surviving. The acute toxicity of CPT-11 was extremely low, particularly in the case of oral administration. CPT-11 is expected to be clinically useful.
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PMID:Antitumor activity of 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxy-camptothec in, a novel water-soluble derivative of camptothecin, against murine tumors. 366 96

CI-921, a 4,5-disubstituted analog of amsacrine, has been selected for clinical testing because of its experimental activity in vitro and in vivo against solid tumors as well as leukemias. In studies conducted by Baguley and co-workers, CI-921 demonstrated activity against Lewis lung carcinoma in vivo, producing marked increases in life span and a high proportion of 60-day survivors. An intermittent schedule of administration was more effective than a daily X 5 or daily X 9 schedule. In pharmacokinetic studies in dogs, CI-921 achieved higher plasma concentrations and was cleared more slowly than amsacrine. CI-921 is readily soluble in water and may have antitumor activity when administered orally. Animal toxicology studies indicate that dose-related, reversible leukopenia and thrombocytopenia occur, as well as gastrointestinal toxicity, elevation of alkaline phosphatase and generalized lymphoid depletion. Phase I clinical testing of a parenteral formulation is in progress.
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PMID:CI-921: an analog of amsacrine with experimental activity against solid tumors. 375 24

Replacement of the 3'-methoxy group of the clinical antileukemic agent amsacrine with a 3'-methylamino group provides a compound (3) with a broader spectrum of action, including in vivo activity against experimental solid tumors. The synthesis, physicochemical properties, and biological activity of a series of acridine-substituted analogues of 3 are described. The compounds show higher levels of DNA binding, water solubility, and in vivo solid tumor activity (lewis lung carcinoma) than their amsacrine counterparts. However, the structure-activity relationships for acridine substitution are different, with 3,5-disubstituted 3'-methylamino compounds showing the highest activity (compared to 4,5-disubstituted amsacrine analogues).
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PMID:Potential antitumor agents. 47. 3'-Methylamino analogues of amsacrine with in vivo solid tumor activity. 375 58

Previous studies have shown that 1 h preincubation with levan caused a sharp decrease in tumorigenicity of tumor cells, although cell viability was not affected. In the present study, the possibility that levan might change the sensitivity of Lewis lung carcinoma cells to the host immune system and that levan might cause delayed damage were tested. Cell morphology, DNA synthesis, cell multiplication and viability as well as osmotic fragility were followed during several days in culture. Levan was found not to affect cell immunogenicity. The polysaccharide destroyed tumor cells by a rather peculiar mechanism: after a seemingly normal or even enhanced growth in culture during 3-5 days, cells suddenly burst. During the apparently normal growth, several morphological changes were observed: cell volume increased, cytoplasm swelled by apparent water uptake and some cells contained two or more nuclei. Levan-treated cells were found to be more susceptible to osmotic shock than non-treated cells. The reason for the sudden cell death could be a gradual increase in volume, up to a point which is no more compatible with membrane integrity, resulting in cell lysis.
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PMID:Slow cytotoxicity of the polysaccharide levan on tumor cells in vitro. 379 87

2-Chloroethyl nitrosocarbamoylcystamine or ICIG-1325 (CNCC) is a lipid-soluble isomeric mixture of nitrosoureas. Its dose-effect relationship on L1210 leukaemia is characterized by a large maximally efficient dose-range (MEDR), greater than that of other nitrosoureas. CNCC also demonstrated significant therapeutic activity on intracerebrally (i.c.) transplanted L1210 leukaemia and on six transplanted solid tumours, TM2 mammary carcinoma, M555 ovarian carcinoma, B16 melanoma, glioma 26, 3LL, Lewis lung carcinoma and colon 26 carcinoma. It was inactive on fibrosarcoma ICIG-Ci4. Its antitumour activity spectrum is wider than that of the related compounds 2-[3-(2-chloroethyl) 3-nitrosoureido]D-glucopyranose (CZT), (chloro-2-ethyl)-1(ribofuranosyl-isopropylidene-2'-3' paranitrobenzoate-5')-3 nitrosourea (RFCNU), and (chloro-2-ethyl)-1 (ribopyranosyl triacetate-2'-3'-4')-3 nitrosourea (RPCNU). A study of its metabolic disposition in animals has shown that CNCC undergoes extensive first-pass metabolism leading to the formation of four main plasma metabolites. These metabolites are water-soluble nitrosoureas that arose from the bioreduction of the disulphide bridge followed by the methylation and the oxidation of the thiol groups. Experimental screening was performed with these chemically synthesized metabolites. Both N'-(2-chloroethyl)-N-[2-(methylsulphinyl)ethyl]-N'-nitrosourea (CMSOEN2) and N'-(2-chloroethyl)-N-[2-(methylsulphonyl)ethyl]-N'-nitrosourea (CMSO2EN2) are very active on L1210 leukaemia grafted intraperitoneally (i.p.) and i.c., L40 leukaemia, B16 melanoma, glioma 26 and Lewis lung carcinoma. Their effectiveness is better than that of the parent compound CNCC. In addition,the percentage of mice cured after CMSOEN2 or CMSO2EN2 treatment is increased especially on B16 melanoma and glioma 26. 6 Haematological toxicity of both active metabolites is lower than that of CNCC, particularly on platelets which is the main toxicity location due to nitrosoureas.
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PMID:Cytostatic action of two nitrosoureas derived from cysteamine. 380 87

Two newly synthesized nitrosoureido sugars have been evaluated for their antitumor activity and diabetogenic potential in a number of in vitro and in vivo preclinical tumor model systems. 2-Amino-2-deoxy-N'-methyl-N'-nitrosoureido-1,3,4,6-tetra-O-acetyl-alpha- D- mannopyranose (MAZ), a lipophilic mannosamine derivative, and ethyl-6-deoxy-3,5-di-O-methyl-6-(3-methyl-3-nitrosoureido)-alph a- D-glucofuranoside (EDOMEN or CGP 6'809), were both found to inhibit L1210 leukemia cell growth in vitro by 50% at approximately 5.0 X 10(-5) M. At these concentrations, little effect was noted immediately on L1210 cell radiolabeled precursor incorporation; however, at higher concentrations, EDOMEN inhibited [3H]leucine and [3H]mannose incorporation, while MAZ specifically decreased L1210 cell [3H]thymidine and [3H]leucine incorporation. Inhibition of Lewis lung carcinoma and B16 melanoma cell growth by 50% in vitro was achieved at higher concentrations of these agents (10(-4) to 10(-3) M). Since the currently available nitrosoureido sugars, streptozotocin and chlorozotocin, have been observed by us to be diabetogenic, EDOMEN and MAZ were evaluated for their specific toxicity to rat pancreatic beta-cells in vitro. Cytotoxicity in beta-cell cultures was monitored both by phase-contrast microscopy and the release of insulin into the culture medium. beta-Cells were found to be 10-fold more sensitive to the toxic effects of MAZ than were pancreatic fibroblasts. EDOMEN, on the other hand, did not damage beta-cells preferentially and therefore was not considered diabetogenic. Both MAZ and EDOMEN had moderate activity as antileukemic agents in mice. At 50 mg/kg/day i.p. for 5 days, MAZ increased the life span of female DBA/2J mice with L1210 leukemia by over 50%. Similarly, doses of EDOMEN at 125 to 250 mg/kg/day i.p. for 5 days increased L1210 leukemic life span by nearly 60%. At these doses, no effect of MAZ was observed on primary Lewis lung carcinoma growth or life span of tumor-bearing C57BL/6 mice. EDOMEN, however, increased life span in Lewis lung carcinoma mice by up to 33% and caused an apparent antimetastatic effect. These studies indicate that EDOMEN may have enhanced value as a cancer chemotherapeutic agent due to its therapeutic effectiveness, lack of diabetogenic potential, and other favorable formulation properties (water solubility) as compared with other clinically available nitrosoureas.
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PMID:Therapeutic and diabetogenic potential of two newly synthesized nitrosoureido sugars. 388 Nov 70

To study the effects of total-body hyperthermia (TBH) on metastases from malignant tumors, Lewis lung carcinoma (LLC)-bearing C57BL/6 mice and mouse ascites hepatoma 134-bearing C3H/He mice were immersed in a heated water bath. Rectal temperature was maintained for 30 min at 40 degrees C or 42 degrees C. After treatment, the incidence of lung metastasis was analyzed in LLC-inoculated mice, and the presence or absence of metastasis in affiliated lymph nodes was determined in mouse ascites hepatoma 134-inoculated mice. A significant inhibition in primary tumor growth in LLC- and mouse ascites hepatoma 134-bearing mice treated with 42 degrees C TBH was noted. The incidence of lung metastasis was increased from the control level of 1.6 +/- 0.63 (SD) to 2.4 +/- 0.98 in the 42 degrees C TBH (P less than 0.01) groups but not in the 40 degrees C TBH group. Metastasis to affiliated lymph nodes was similar for the controls and the 40 degrees C and 42 degrees C TBH groups. The increase in lung metastasis in LLC-treated mice subjected to 42 degrees C TBH could be prevented by the combined use of anticancer drugs such as cis-diamminedichloroplatinum(II) (1.0, 3.0 mg/kg) or mitomycin C (0.3, 1.0 mg/kg). Furthermore, the combined use of 42 degrees C TBH and anticancer drugs showed the inhibition of primary tumor growth to a greater degree than did 42 degrees C TBH alone or anticancer drugs alone. Since 42 degrees C TBH may induce tumor metastasis, especially hematogenous metastasis, it seems advisable to use anticancer drugs in combination with clinical thermal applications.
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PMID:Effects of total-body hyperthermia on metastases from experimental mouse tumors. 391 41

To study the effects of total-body hyperthermia (TBH) and local one (LH) on tumor metastases in animal experiments, heat was delivered to Lewis lung carcinoma (LLC)-bearing C57BL/6 mice and mouse ascites hepatoma-134 (MH-134)-bearing C3H/He mice, by water bath immersion systemically and locally. Rectal temperature in TBH was kept at 40 or 42 degrees C, while intratumor temperature in LH, at 40, 42, or 43 degrees C, respectively for 30 min. Also backgrounds of spread of lung metastasis of LLC in the case of TBH at 42 degrees C have been investigated as well as strategic preventive measures for it. The following results were obtained: The growth of primary LLC and MH-134 tumors was inhibited by TBH and LH at 42 degrees C and LH at 43 degrees C. The lung metastases of LLC increased by TBH at 42 degrees C. The lymph node metastases of MH-134 decreased by LH at 43 degrees C. The increase of lung metastases of LLC by 42 degrees C TBH occurred within 24hr after the session, presumably due to the increase in intravascular invasion of tumor cells and accelerated implantation of them according to histological changes of lungs. The observable tendency toward lung metastases continued for 48hr after treatment, coincidentally with distinctness in observation of histological changes. The increase mentioned above could be prevented by combined use of 42 degrees C TBH with anticancer drugs, as cis-diamminedichloroplatinum II or mitomycin-C. This combination resulted in further inhibition of tumor growth of primary LLC also, than non-combined 42 degrees C TBH. Considering the above facts, combined treatment of TBH with anticancer drugs is believed much valid clinically, in preventing metastases and making higher exertions of antitumor effects.
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PMID:[Experimental studies on effects of total-body and local hyperthermia on metastases in mice]. 392 May


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