Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pentoxifylline (PENTO), a derivative of methylxanthine, has been reported to improve fluidity of red blood cells (RBC), and thus improve the flux of RBC through narrow capillaries. Additionally, PENTO increases 2,3-DPG levels in RBC, thereby increasing the O2 release from RBC. Nicotinamide (NA) has been known to increase tumor blood flow, reducing the hypoxic cell fractions in the tumors. The purpose of this study was to examine the effects of PENTO alone or in combination with NA (PENTO + NA) on the oxygenation and radio-response of FSaII murine fibrosarcomas of mice. We observed a significantly enhanced, radiation-induced growth delay of the FSaII tumors by the treatment of either single or multiple injections of PENTO. The combination of PENTO and NA further delayed the growth of tumors. The TCD50 of control tumors was about 56.6 Gy, whereas that of PENTO + NA treated tumors was about 31.9 Gy. Thus, TCD50 was modified by a factor of 1.8. PENTO + NA exerted no effect on the acute skin damage of C3H mice after local irradiation and the gastrointestinal death after whole body irradiation. However, PENTO + NA slightly increased the bone marrow death as demonstrated by the decrease in LD50(30) from 5.5 Gy to 5.2 Gy. The average pO2 in the saline-treated control group of FSaII tumors was 8 mmHg and it significantly increased to 19 mmHg in the PENTO + NA treated group (p less than 0.001). We concluded that the PENTO + NA treatment increased the radio-response of tumors by improving tumor oxygenation.
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PMID:Increases in tumor response by pentoxifylline alone or in combination with nicotinamide. 153 Dec 11

The response of the rhabdomyosarcoma R1H of the rat to fractionated irradiation has been reported to be almost independent of the dose per fraction in the range from 0.43 to 10 Gy. To elucidate whether recovery from radiation injury is impaired in fractionated irradiation or not, tumours were exposed on 5 days per week over 6 weeks either to a single daily dose or to two daily fractions separated by an interfraction interval of 2 h. Tumour response was assessed by net growth delay. Skin damage was scored for comparison. A significant reduction in tumour response (p less than 0.009) and skin damage (p less than 0.001) was observed when the daily dose was administered in a twice daily irradiation regimen, indicating that recovery from radiation injury does occur in the course of fractionated irradiation in our tumour system. A tumour response was almost independent of the dose per fraction for time intervals between fractions of at least 8 h, a possible explanation might be that recovery is compensated by improved reoxygenation.
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PMID:Radiotherapy of the rhabdomyosarcoma R1H of the rat: recovery from radiation injury in tumour and skin. 154 85

A new photosensitizer, LCP, a combination of lysyl chlorin p6 and chlorin p6, was synthesized and tested for effectiveness in photodynamic therapy using s.c. implanted 9L glioma tumors in rats. Tumors were irradiated with 664-nm light 4 h after LCP injection. Mean intratumoral temperature elevations were less than 4 degrees C using a power density of 50 mW/cm2 for 33.3 min (100 J/cm2). Subsequent experiments examining histological changes and tumor regrowth used a power density of 50 mW/cm2 and total energy densities of 25, 50, and 100 J/cm2. Microscopically, an energy density-dependent coagulation necrosis of tumor cells occurred in treated tumors. Long term inhibition of tumor growth was achieved only at an energy density of 100 J/cm2. Side effects of treatment were seen only in the irradiated area and consisted of coagulation necrosis of normal tissues in rats treated at 50 and 100 J/cm2, including severe skin necrosis. Exposure of rats to fluorescent room light did not cause any macroscopically detectable skin damage. Our data indicate that photodynamic destruction of s.c. 9L glioma tumors using LCP as a photosensitizer results in significant tumor growth inhibition and that further study of LCP is warranted.
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PMID:Effectiveness of a lysyl chlorin p6/chlorin p6 mixture in photodynamic therapy of the subcutaneous 9L glioma in the rat. 173 84

The interaction among nicotinamide, radiation, and heat was studied in vivo using a C3H mouse mammary carcinoma grown in the feet of CDF1 mice. Response following local tumor treatment was assessed by tumor control and regrowth delay. Nicotinamide (1000 mg/kg i.p.) produced maximal radiosensitization when injected 30 min to 2 h before irradiation [enhancement ratios (ERs), 1.2-1.5]. Radiation damage was also increased by heating tumors (43.5 degrees C for 60 min) 4 h after irradiation (ERs = 1.6-2.6). This combined radiation and heat treatment was enhanced by nicotinamide but the effect depended on the assay procedure, such that although a significant increase was observed with the tumor control assay, only a slight increase was seen using regrowth delay as the end point. The development of moist desquamation in normal feet was used to estimate skin damage after irradiation. Nicotinamide and heat both resulted in a small yet significant increase in skin damage (ERs less than 1.2 and 1.1, respectively). A combined treatment resulted in a greater ER of 1.7, but when compared to the tumor response it still gave a therapeutic gain. A histological fluorescent staining technique was used to assess functional tumor vasculature at two periods in time separated by 20 min. Under normal conditions 7.7% of the vessels in this tumor were functional at one time but not the other. This value was reduced to 2.8% after nicotinamide administration. Since these fluctuations in blood flow can result in acute hypoxia we conclude that while heat eliminates chronically hypoxic tumor cells, nicotinamide probably removes the presence of acute hypoxia.
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PMID:Combination of nicotinamide and hyperthermia to eliminate radioresistant chronically and acutely hypoxic tumor cells. 214 77

Mono-L-aspartyl chlorin e6 (NPe6) is a photosensitizer that possesses properties such as chemical purity and a major absorption band at 664 nm which are potentially exploitable for photodynamic therapy (PDT). The current investigation examined pharmacological and photosensitizing parameters of NPe6 in tumor and normal tissues in mice. [14C]NPe6 was used to obtain quantitative tissue distributions of the photosensitizer as a function of: (a) time following administration; (b) drug dose; (c) mode of drug administration; and (d) tumor size. The in vivo photosensitizing efficiency of NPe6 was compared directly to Photofrin II in experiments which evaluated tumor responses and induction of normal skin damage. Initial PDT experiments demonstrated that NPe6 was ineffective at inducing tumor cures when a 24-h time interval (between drug administration and light treatment) was used. However, PDT-induced tumor cures were obtained when NPe6 was administered 4-6 h prior to light exposure, and these NPe6-PDT treatment parameters were as effective as standard Photofrin II-mediated PDT. Interestingly, the level of PDT-induced normal skin damage was significantly greater for Photofrin II than for NPe6 at comparable drug and light doses. An analysis of pharmacological data and PDT time interval requirements suggests that plasma concentrations of NPe6 may be a more important predictive factor than tumor tissue levels of the photosensitizer for the production of PDT-mediated tumor cures. The results of this investigation indicate that NPe6 is an effective tumor photosensitizer with in vivo clearance properties that eliminate the side effect of prolonged normal skin photosensitization.
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PMID:Tissue distribution and photosensitizing properties of mono-L-aspartyl chlorin e6 in a mouse tumor model. 235 46

The present study compared the antitumor activities of chemotherapy with 5-fluorouracil (5-FU) and with its prodrug 5'-deoxy-5-fluorouridine (5'-DFUR) in combination with radiotherapy on a solid colon 26 adenocarcinoma in the mouse. A single administration of 5'-DFUR immediately after local irradiation on day 10 after tumor inoculation produced more than additive antitumor effects, while only an additive effect was observed in the combined treatment with 5-FU and radiation. This over-additive effect of 5'-DFUR was more obvious in a fractionated-dose treatment schedule, where the same combined modality treatment was given three times on days 6, 10 and 14 after inoculation of the tumor cells. 5'-DFUR enhanced the radiation effects on the tumor in terms of the delay in tumor growth as well as the increase in the survival time. 5-FU produced only a marginal additive antitumor effect. Furthermore, radiation damage to normal tissues (skin damage by local irradiation and bone marrow and spleen damage by whole-body irradiation) was not enhanced by 5'-DFUR, though radiation damage to the thymus was additive. On the other hand, 5-FU produced toxic effects that were additive for all normal tissues tested. Thus, at doses that were the most effective against tumors, relative therapeutic gain factors (the ratio of the effect on tumors to that on the bone marrow) of 5'-DFUR and 5-FU were 1.24 and 0.49, respectively. These results suggest that 5'-DFUR will have a greater potential than 5-FU in combined modality treatment of cancer patients.
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PMID:Comparative antitumor activity of 5-fluorouracil and 5'-deoxy-5-fluorouridine in combination with radiation therapy in mice bearing colon 26 adenocarcinoma. 252 17

BD IX rats with BT4An tumours subcutaneously on the hind leg were stratified after tumour size and treated by single dose 44 degrees C water bath hyperthermia for 90 minutes or with two 45 minute sessions at 24, 48 or 168 hour intervals. Other groups were treated by single dose BCNU at 20 mg/kg or by two divided doses at the same intervals, or by combined hyperthermia and drug as single treatment or as divided treatments at the same intervals. Intratumoural temperatures in some animals were carefully scanned for minimal temperature during two hyperthermia sessions 24 hours apart. Tumour response, normal skin damage and weight was evaluated. It was concluded that single dose hyperthermia and combined treatment yielded the best effect, but also resulted in the most severe skin reaction and weight loss. Hyperthermia was least effective at a 24 hour interval, indicating thermotolerance to be greatest at this time. The minimum intratumoural temperatures were higher at the second heat dose given at 24 hours, demonstrating a poorer ability to dissipate heat after the first treatment. The tumours were only slightly sensitive to BCNU alone, and no optimal schedule was found. BCNU increased the hyperthermia effect at all schedules, except for the 168 hour interval. The skin reaction to single dose hyperthermia was enhanced by BCNU.
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PMID:Hyperthermia or BCNU alone and combined in BD IX rats with BT4An tumours. Effects of a single or two equal fractions at different intervals. 297 49

The effects of step-up (42----44 degrees sequence) and step-down (44----42 degrees sequence) heating were studied on a transplantable mammary adenocarcinoma of C3H/He mouse. Tumor-bearing legs were immersed in a water bath and the response to hyperthermia was evaluated in terms of the delay in tumor growth. Tumor growth was delayed greatly with increase in the duration of treatment with 44 degrees hyperthermia, whereas with 42 degrees hyperthermia of up to 180 min, tumor growth was delayed only slightly. The effects of step-up heating were similar to those of 44 degrees hyperthermia alone and the response was enhanced by a factor of 0.9-1.1 with the 60-min treatment at 42 degrees followed by treatment at 44 degrees. Thermal resistance developed when the preheating time at 42 degrees was longer than 30 min. On the other hand, the tumor response was markedly enhanced by step-down heating by a factor of 1.8-2.4 with the treatment at 44 degrees followed by 60-min treatment at 42 degrees. Since the enhancement factor for skin damage found previously was similar to that for the tumor, therapeutic gain cannot be expected by the use of these combined heat treatments.
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PMID:Effects of step-up and step-down heating on a transplantable murine tumor. 309 20

The effect of Fluosol DA 20%, an emulsion of perfluorochemicals, in combination with carbogen (95% O2 and 5% CO2) breathing on the response of mouse tumors to radiation was studied. When A/J mice bearing SCK tumors in the right hind limb were injected iv with Fluosol DA 20% at 12 ml/kg and exposed to carbogen for 1 h before and during the irradiation of tumors, the response of tumors to a single dose of X irradiation was significantly enhanced. The dose modification factors for growth delay and cure of SCK tumors were 2.10 +/- 0.01 (SE) and 1.86 +/- 0.18 (SE), respectively. Such a treatment slightly increased the radiation-induced skin damage by a factor of 1.17 +/- 0.02 (SE), resulting in a therapeutic gain of 1.79 +/- 0.01 (SE) for the growth delay and 1.59 +/- 0.09 (SE) for the curability. Carbogen breathing alone also increased the response of tumor and skin to radiation, but it was far less effective than the combination of Fluosol DA 20% and carbogen breathing. It was concluded that iv injection of Fluosol DA 20% in conjunction with carbogen breathing significantly increased the O2 transport to hypoxic areas in the SCK tumors and thus significantly enhanced the tumoricidal effect of radiation on SCK tumors.
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PMID:Effects of Fluosol DA 20% and carbogen on the radioresponse of SCK tumors and skin of A/J mice. 311 97

The influence of the number of fractions on tumor and skin response to fractionated irradiation was studied. R1H rhabdomyosarcomas of the rat (volume doubling time 3 days) were irradiated with 6, 18, 30, or 42 fractions in 6 weeks. Total doses of 45, 60, or 75 Gy were applied in each fractionation scheme, that is, the dose per fraction ranged from 1.07 to 12.5 Gy. Tumor response was assessed by tumor control probability and tumor net growth delay. A clearcut reduction of skin damage was observed with increasing number of fractions, whereas the tumor response was found to be the same whether the dose was given in 6, 18, 30, or 42 fractions. Thus, the fractionation regimens were more effective than expected from calculations based on single-dose in situ survival curves. This result can be explained by assuming that the clonogenic tumor cells become less hypoxic with increasing number of fractions. Since normal tissue damage decreases with increasing number of fractions, the therapeutic gain may be improved by applying a greater number of fractions.
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PMID:Radiotherapy of the rhabdomyosarcoma R1H of the rat: the influence of the number of fractions on tumor and skin response. 334 56


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