Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0598934 (tumor growth)
 58,965 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The influence of eicosanoids on the proliferation of hepatoma (HTC) cells was studied in culture and in tumor-bearing rats. The cells in culture demonstrated a capacity to metabolize arachidonic acid to eicosanoids including thomboxane B2 and the prostaglandins E2 and F2 alpha a. An effect of these eicosanoids on cell proliferation was suggested by the decreased cell division seen with an inhibitor of cyclooxygenase, flurbiprofen. A biphasic effect on the proliferation of HTC cells was observed with increasing concentrations of prostaglandin F2 alpha. These studies were extended to tumor-bearing rats where inhibitory effects on the early stages of tumor growth were seen with flurbiprofen. Bleeding times were decreased in tumor-bearing rats but were restored to control values by treatment with flurbiprofen and an inhibitor of thromboxane synthetase, OKY 046. These drugs and a thromboxane/endoperoxide receptor antagonist, SQ 29, 548, were not observed to have statistically significant effects on isotope-labeled water distribution but they had substantial effects on the maintenance of body weight by tumor-bearing rats. The data suggested that the cachexia of tumor-bearing animals may be mediated at least in part by the action of eicosanoids.
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PMID:Influence of inhibitors of eicosanoid metabolism on proliferation of rat hepatoma cells and on tumor-host interaction. 211 60

The objective of the present investigation was to compare the effects of three ornithine decarboxylase inhibitors on tumoricidal macrophage and antitumor activities in vivo. alpha-Difluoromethylornithine (DFMO), (2R,5R)-6-heptyne-2,5-diamine, and alpha-(fluoromethyl)dehydroornithine methyl ester (delta MFMOme) were administered continuously in drinking water starting on Day 1 to B16F1 tumor-bearing mice. DFMO, (2R,5R)-6-heptyne-2,5-diamine, and delta MFMOme reduced B16F1 tumor growth, measured on Day 18, up to 87, 79, and 95%, respectively. Similarly, all three ornithine decarboxylase inhibitors reduced B16F1 putrescine and spermidine levels. delta MFMOme was substantially more effective both as an antitumor agent and in reducing polyamines. Both DFMO and delta MFMOme augmented macrophage tumoricidal activity directed against B16F1 target cells. MAP had no effect on macrophage tumoricidal activity. Lipopolysaccharide-stimulated macrophages from delta MFMOme-treated mice also exhibited an increase in interleukin and tumor necrosis factor levels. Furthermore, treatment with a known macrophage activator, gamma-interferon, enhanced the antitumor activity of delta MFMOme. delta MFMOme did not alter natural killer cell activity; however, cytolytic T-lymphocyte induction was reduced by 40 to 50%. These results demonstrate that, in addition to their established antitumor activity, ornithine decarboxylase inhibitors may also potentiate specific tumoricidal effector cell generation in vivo.
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PMID:Effects of three irreversible inhibitors of ornithine decarboxylase on macrophage-mediated tumoricidal activity and antitumor activity in B16F1 tumor-bearing mice. 211 41

A study of hyperthermia was performed after injection of 0.5 mg/kg of MMC into feeding artery of Walker 256 implanted 4 days (early stage) or 8 days (advanced stage) earlier into the s.c. dorsum side of hindpaw of Wistar rats. The tumor growth curves on 6 days after treatment by warming tumor in hot water (44 degrees C) for 60 minutes were inhibited in advanced stage group which formed tumor vessels, but not in the early stage which had not still formed them. An intraarterial injection of warmed 0.01 to 0.05% Noradrenaline solution (44 degrees C, 10 ml) after chemotherapy (0.5 mg/kg of MMC a.i.), by which the temperature did not rise in the tumor tissue but rose to 40 degrees C for 5 to 10 minutes in the tumor vessels, showed severe cytotoxic damage in advanced stage group. The warming target of the tumor for hyperthermia can be considered to be the tumor vessels. Warmed 5% glucose using 0.1 mg of Noradrenaline (500 ml, 44 degrees C) injected into the tumor feeding artery after chemotherapy (2 to 6 mg of MMC or 250 mg of 5-FU a.i.) was tried in advanced cancer patients (liver tumor 4 cases, pancreas tumor 1 case, metastatic bone tumor 1 case, and multicentric tumor in liver, gall bladder and pancreas 3 cases). Efficacy was noted in 8 cases at the rate of 72.7% (8/11). It was concluded that warmed Noradrenaline solution delivered to the tumor vessels after chemotherapy for advanced cancer resulted in good efficacy rate as a from of chemo-thermotherapy.
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PMID:[Warm drug solution injected into tumor vessel may enhance antitumor effect]. 211 3

We examined the influence of different shock wave application modes with a Dornier XL1 electrohydraulic lithotripter on the growth of A-Mel 3 and SSK2 tumors implanted under the dorsal skin of hamsters or mice. In a basic protocol, 500 shock waves a day on 4 consecutive days were administered at a discharge rate of 100 waves per minute and focused to the tumor center. This did not affect A-Mel 3 growth. A similar result was obtained with the basic protocol modified to 1000 shock waves a day and a wave application rate of 100 shock waves per second. Growth of A-Mel 3 and SSK2 tumors was significantly delayed, when the basic protocol was used, but the 500 shock waves a day were distributed over four points at the tumor edges and the tumor center. With the same shock wave protocol, lowering the water level over the tumor from 10 cm to 1 cm induced temporary regressions of SSK2 tumors. This was not due to the higher energy applied to the tumor, since twice the number of shock waves (1000 a day instead of 500 a day) was applied at a high water level and did not induce regressions. Four consecutive treatments with intervals between treatments shortened to 3 h and an additional treatment 12 h later at a low water level completely controlled tumor growth in 8 out of 12 SSK2 tumors for more than 150 days. The result showed that addition of a reflected wave from the water surface was most important for the shock wave effect, and suggested that shock wave devices generating similar wave forms should be applied for tumor therapy.
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PMID:Influence of the shock wave application mode on the growth of A-Mel 3 and SSK2 tumors in vivo. 223 68

By a sensitive and quantitative fluorometric assay, brain and plasma time-dependent concentration profiles were generated for phosphoramide mustard (PM) and active alkylating metabolites derived from cyclophosphamide (CPA) administration to rats. Whereas PM rapidly disappeared from plasma, with a monophasic half-life of 15.1 min, equimolar administration of CPA generated active metabolites in plasma that disappeared monoexponentially, with a composite half-life of 63 min. As a consequence, the time-dependent concentration integral of active alkylating metabolites derived from CPA administration, calculated between 5 min and infinity, was 3-fold that of PM. Pharmacokinetic parameters were calculated for each compound. The brain/plasma concentration-integral ratios of PM and active alkylating metabolites derived from CPA were 0.18 and 0.20, respectively. The cerebrovascular permeability-surface area product of PM was 7.5 x 10(-5) s-1, which is similar to that of other water-soluble anticancer agents that are restricted from entering the brain. The activities of a range of daily doses of PM and CPA were assessed against subcutaneous and intracerebral implants of Walker 256 carcinosarcoma tumor in rats. Inhibition of subcutaneous tumor growth by 50% was caused by CPA and PM doses of 6.6 and 12.0 mg/kg (daily for 5 consecutive days, starting 36 h after tumor implantation), respectively. However, administration of daily doses of up to 40 mg/kg did not significantly increase the survival of animals with intracerebral tumor implants. These studies indicate that active metabolites of CPA are restricted from entering the brain and that only subtherapeutic concentrations are achieved in brain tissue after systemic administration of CPA or PM.
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PMID:Brain and plasma pharmacokinetics and anticancer activities of cyclophosphamide and phosphoramide mustard in the rat. 224 87

If proton nuclear magnetic resonance (1H NMR) spectroscopy is to provide a clinically useful modality for monitoring tumor growth and treatment, the technique must be able to unambiguously detect steady-state metabolite concentrations in human tumors and differentiate these from normal tissue levels. To address this problem, a two-dimensional double quantum coherence transfer spectroscopy (2DDQCT) method was developed and tested in a series of tumor cell lines implanted in mice. Lactate-edited proton NMR spectra were determined from a roughly 1-cm3 region of interest in EMT6, RIF-1, and fibroma. In two-dimensional data matrix representations of the 2DDQCT experiments (double quantum frequency on the vertical axis and chemical shift on the horizontal axis) the lactate signal (330 Hz with the transmitter set at the water resonance) was well-resolved from lipid (480 Hz, 600 Hz). The resolution in the double quantum dimension was also sufficient to conclude that a detectable level of alanine, which would reside at 358 Hz, was not present in the three tumor types. Following the NMR experiment, tumors were chemically assayed for lactate giving 8.17, 9.1, and 6.73 mumols/g wet wt for RIF-1, EMT6, and fibroma, respectively. This technique is likely to provide a noninvasive method for monitoring the steady-state lactic acid levels in small tumors before and after therapy, as well as in tissues with impaired oxygen delivery using clinical and research NMR systems.
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PMID:A double quantum coherence transfer proton NMR spectroscopy technique for monitoring steady-state tumor lactic acid levels in vivo. 234 12

The efficacy of heparin (HEP), the heparin analogue hexuronyl hexosaminoglycan sulfate (HHS), and hydrocortisone (HC) was studied in inhibiting the growth of four morphologically distinct pancreatic adenocarcinoma lines (CBP, LHP2, LSP3, and Pour-LVG) in hamsters. Animals were inoculated with LD100 doses of one of the four tumor lines and were randomly allocated to groups of five animals, which received in their drinking water either: HEP (1000 U/ml) alone, HHS (10 mg/ml) alone, HC (0.5 mg/ml) alone, HEP plus HC, HHS plus HC, or no additives (control). Tumors were measured, growth rates calculated, and nonparametric statistical comparisons made among the median growth rates of all of the treatment groups. All four tumors were tested in the rabbit cornea assay for their ability to induce angiogenesis. Extracts of tumors from control animals as well as from animals treated with HHS plus HC were prepared for quantitative testing in vitro by endothelial cell migration assay. All four tumor lines caused angiogenesis as measured in the rabbit cornea assay. A reduction in median tumor growth rates was observed in animals treated with HHS plus HC bearing the CBP, Pour-LVG, and LSP3 tumors. Similarly, in vitro capillary endothelial cell migration was decreased by HHS plus HC treatment in animals bearing CBP, Pour-LVG, and LSP3 tumors. Animals bearing the LHP2 tumor showed no effect of HHS plus HC treatment on tumor growth rate and no effect on endothelial cell migration. HEP alone, HHS alone, HC alone, and HEP plus HC showed no effect on tumor growth rate in any of the four tumors tested.
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PMID:Inhibition of tumor angiogenesis by hexuronyl hexosaminoglycan sulfate. 241 79

The effect of "antiangiogenesis" therapy using cortisone acetate (CA) with or without heparin on tumor growth as well as in combination with chemotherapy was investigated. C3H mice were implanted intradermally with N-[4-(5-nitro-2-furyl)-thiazolyl]formamide induced undifferentiated transitional cell carcinoma, MBT-2, in the right flank. The treatment was initiated 9 to 10 days after tumor inoculation. Daily injections of CA (250 mg/kg s.c.) suppressed tumor growth significantly in a dose dependent fashion. Administration of heparin (Elkins-Sinn) at the concentration of 200, 400, or 1000 units/ml in drinking water for 3 to 6 days was neither additive nor detrimental to the effect of CA. Chemotherapy was combined with CA; 3 days of administration of 250 mg/kg of CA in tapering doses was used. The chemotherapeutic agent was injected once 24 h before the initial CA. Combinations of chemotherapy (Adriamycin, 2.5-7.5 mg/kg i.v; cisplatin, 3-9 mg/kg i.p.; cyclophosphamide, 50-150 mg/kg i.p.; cis-(diammino)(1,1-cyclobutanedicarboxylate)platinum(II) (JM-8), 60-150 mg/kg i.p.; mitomycin C, 3-4.5 mg/kg i.p.) with CA showed additive suppression of tumor growth. Mice tolerated chemotherapy alone, CA alone, and both in combination. CA combined with JM-8 was not tolerated. Mice tolerated 100 to 150 mg/kg of JM-8, whereas the addition of CA to JM-8 resulted in a 66% (6 of 9) to 89% (8 of 9) mortality rate. CA at a concentration of 5 and 25 micrograms/ml showed no direct cytotoxic activity against MBT-2 cells in vitro. However, 3 days of administration of 250 mg/kg of CA inhibited tumor angiogenesis generated by MBT-2 cells in C3H mice using a dorsal air sac assay. The data suggest that CA alone inhibits tumor angiogenesis in C3H mice and that antiangiogenesis therapy enhances the antitumor efficacy of chemotherapeutic agents without increasing host toxicity (except for JM-8).
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PMID:Efficacy of antitumor chemotherapy in C3H mice enhanced by the antiangiogenesis steroid, cortisone acetate. 244 60

Temperature-sensitive liposomes are designed to break down and release their contents preferentially at temperatures attainable by local hyperthermia. The antitumor effects of hyperthermia and anticancer drugs selectively delivered by temperature-sensitive liposomes in metastatic lymph nodes in rats were determined. Temperature-sensitive liposomes containing bleomycin (BLM) were injected sc into the dorsal surface of the right hindfoot of rats bearing AH66 ascites tumor implanted 7 days previously into a right popliteal lymph node. To break down these temperature-sensitive liposomes preferentially in the metastatic lymph nodes and to achieve the synergistic effects of local hyperthermia and BLM, we applied local hyperthermia to the right popliteal lymph node by making use of a water bath at 44 degrees C for 20 minutes. There was a significant difference in suppression of tumor growth and prolonged survival in rats receiving both temperature-sensitive liposomes containing BLM and local hyperthermia, compared with groups receiving hyperthermia alone, water solution of BLM alone, or a combination of both (P less than 0.05). The possibility that hyperthermia plus temperature-sensitive liposomes will enhance therapy for patients with metastatic lymph nodes warrants attention.
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PMID:Selective treatment of metastatic lymph nodes with combination of local hyperthermia and temperature-sensitive liposomes containing bleomycin. 244 81

We have previously established that type I interferon (IFN), a mixture of alpha- and beta-IFN, augments the antitumor activity of alpha-difluoromethylornithine (DFMO), an inhibitor of polyamine biosynthesis, against B16 melanoma. The objective of the present investigation was to extend these earlier observations to metastatic Lewis lung carcinoma and to determine specifically which component(s) of type I IFN potentiates the antitumor activity of DFMO. Furthermore, we wanted to determine whether type II (gamma) IFN can also potentiate the antitumor activity of DFMO. Treatment of animals bearing Lewis lung carcinoma with DFMO, 2% in drinking water (3 g/kg/day), or IFN-alpha/beta (1000 units/mouse) given subcutaneously on alternate days for a total of ten doses alone resulted in 42 and 5% inhibition of tumor growth, respectively. A combination of DFMO and interferon brought about complete elimination of tumors in 12 of the 18 animals, and 94% inhibition of tumor growth in the remainder. DFMO or type I IFN administered alone caused 94 and 26% inhibition of metastasis, respectively. Combination treatment with these two agents resulted in complete elimination of visible metastases. Treatment of mice bearing B16 melanoma with DFMO resulted in 81% inhibition of tumor growth compared to controls. The administration of interferons alone resulted in tumor growth inhibition of 15, 3, 1, and 43% for type I, alpha-, beta-, and gamma-interferons, respectively. Treatment of animals with combination of DFMO and various interferons resulted in inhibition of 94, 93, 86, and 94% of B16 tumor growth for type I, alpha-, beta-, and gamma-interferons, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of murine alpha-, beta-, and gamma-interferons in combination with alpha-difluoromethylornithine, an inhibitor of polyamine biosynthesis, on the tumor growth and metastasis of B16 melanoma and Lewis lung carcinoma in mice. 249 64


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