Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0029463 (osteosarcoma)
 16,637 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a Mayo Clinic prospective study of metastasis from osteogenic sarcoma, so-called prophylactic whole-lung irradiation (a 1,500-rad tumor dose to the whole of both lungs, in divided doses, with oxygen and actinomycin) proved ineffective. 14 patients underwnet an operation for metastatic pulmonary disease. The earlier the excision of a metastatic lesion, the greater the chance of an effective cure. Preoperative irradiation of the bone tumor had no positive effect. The primary lesion should also be excised as soon as possible. Surgical removal of a tumor should be followed by immunotherapy or chemotherapy or both. The rate of reliably "cured" cases could be improved by extensive studies of immunologic reaction before and after surgical intervention.
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PMID:Management of osteogenic sarcoma at the Mayo Clinic. 82 96

The present study was undertaken to explore the relationship of the time interval between application of heat and irradiation on enhanced tumor cell sensitivity. Using the Ridgway osteogenic sarcoma grown in AKD2F1/J mice, local tumor hyperthermia (42.5 +/- .5 degrees C for 15 minutes) was applied at various time intervals before or after single or fractionated doses of x irradiation. Enhancement of tumor cell sensitivity by combined treatment with radiation and heat, as measured by delay in tumor growth, cure rates, and mean survival times was inversely proportional to the time interval between application of both modalities. The interactions associated with this increased sensitivity appear to be transitory, diminishing with time between treatments. Possible mechanisms of action for thermal sensitization may involve the reduction of oxygen dependence as well as a reduced recovery capacity of tumor cells.
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PMID:The relationship between the time of fractionated and single doses of radiation and hyperthermia on the sensitization of an in vivo mouse tumor. 105 37

More than 200 nitro compounds, most of them nitroaniline derivatives substituted with one or more radicals having a basic reaction, were prepared and investigated as to their therapeutic activity against bacteria, fungi, protozoa, helminths, viruses and tumors. Several mono-nitrobenzenes with a radical having a basic reaction showed weak in-vitro activity against gram-positive bacteria and against Crocker's sarcoma 180; they also showed systemic activity against nematodes (Aspiculuris tetraptera) and viruses. The majority of therapeutically active compounds with pronounced in-vivo activity against Trichomonas fetus, Entamoeba histolytica, Schistosoma mansoni, cestodes, nematodes (Ancylostoma caninum), viruses (influenza, MHV, SAV and EMC) and various types of carcinoma (Ehrlich's carcinoma, leukemia 1210, Crocker's sarcoma 180) were dinitrobenzene derivatives with one radical having a basic reaction and electropositive groups or unreactive or reactive chlorine atom, and di-nitrobenzene with two equal or two different radicals having a basic reaction. Compound No. 70 revealed a marked in-vitro activity against fungi (Trichophyton; Microsporum, Candida albicans). Other nitro compounds such as bis-mono- and bis-dinitrobenzene derivatives likewise showed a systemic action against E. histolytica, viruses and, in particular, carcinoma (Crocker's sarcoma 180, Ridgway's osteosarcoma). Oxygen and sulfur analogue compounds as well as compounds produced by reduction also possessed a distinct activity against E. histolytica and viruses. On the basis of the present results particularly the dinitrobenzenes substituted with two radicals having a basic reaction include a number which have in common that a structure/activity relationship is recognizable in respect of E. histolytica, Schistosoma mansoni and different types of viruses. The activity against viruses in this class of compounds is probably due to an increased interferon production in the host animal. Whether the mechanism of action is the same against E. histolytica or Schistosoma mansoni has not been determined so far. A tumorigenic effect was observed mainly in those di-nitrobenzenes which are classed as alkylating compounds. Because of the small chemotherapeutic index the trials were not continued with the most effective compounds mentioned.
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PMID:[Chemotherapeutic effects of nitro compounds. 1. Nitroanilines]. 124 9

Fluoromisonidazole labeled with H-3 or F-18 has been tested as a quantitative probe for hypoxic cells in vitro and in rodent and spontaneous dog tumors in vivo. In V-79, EMT-6(UW), RIF-1, and canine osteosarcoma cells in vitro, the binding of 50 microM [H-3]Fluoromisonidazole was 50% inhibited by 1000-2000 ppm O2, relative to binding under anoxic conditions. After a 3 hr incubation with labeled drug, the anoxic/oxic binding ratios ranged from 12 to 27 for the four cell types. Retention of [H-3]fluoromisonidazole 4 hr after injection was greater in large KHT tumors (400-600 mm3) with an estimated hypoxic fraction greater than 30%, than in smaller tumors (50-200 mm3) with an estimated hypoxic fraction of 7-12%. RIF-1 tumors, with an estimated hypoxic fraction of 1.5%, retained the least label, with tumor: blood ratios ranging from 1.7 to 1.9. Spontaneous dog osteosarcomas were imaged with a time of flight positron emission tomograph for up to 5 hr following injection of [F-18] fluoromisonidazole. Analysis of regions of interest in images allowed creation of dynamic tissue time activity curves and calculation of tissue uptake in cpm/gram. These values were compared to radioactivity in plasma. In all cases, retention in some tumor regions exceeded that in plasma and in normal tissue, such as muscle or brain, by 3 to 5 hr post injection. Uptake of fluoromisonidazole in tumors was heterogeneous, with ratios of maximum to minimum uptake as high as 4 in different regions of interest in the same tumor. Tumor:plasma values ranged from 0.28 to 2.02. The oxygen dependency of fluoromisonidazole retention was similar in a variety of cell types and was 50% inhibited by O2 levels in the transition between full radiobiological hypoxia and partial sensitization. The quantitative regional imaging of [F-18] fluoromisonidazole in spontaneous canine tumors at varying times post-injection lays the basis for imaging and modeling of oxygen-dependent drug retention in different regions of human neoplasms.
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PMID:Radiolabelled fluoromisonidazole as an imaging agent for tumor hypoxia. 280 61

Six different types of spheroids of both human and rodent origin were cultured, using the liquid-overlay technique. Oxygen gradients were measured with micro-electrodes, when the spheroids were attached to thin cover-glasses. The gradients were measured from the upper surface towards the center of the spheroids. Stable and reproducible gradients were obtained. Large variations were seen in the steepness of the gradients, depending both on the type and on the size of the spheroids. An interesting phenomenon was discovered. When some types of spheroids were cultured in a medium with a low oxygen pressure (medium equilibrated with gas containing 4-5% O2), the gradients continuously changed and became flatter. Detailed studies showed that most of the changes occurred within 2 days after the transfer to the low oxygen pressure. After 2 days, no further dramatic changes took place. This phenomenon was seen in two types of human glioma (U-118 MG and U-178 MG) and two types of embryonic, hamster lung-cell (V-79-379A and CHEL) spheroids. In the cases of human-osteosarcoma (U-393 OS) and human thyroid-cancer (HTh7) spheroids, no such changes could be seen. The low oxygen tension in the culture medium was chosen to mimic the environmental conditions in solid tumors.
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PMID:Influence of the oxygen pressure in the culture medium on the oxygenation of different types of multicellular spheroids. 385 48

We determined the energy cost during gait by measuring the oxygen consumption of twenty-six patients after treatment for osteosarcoma about the knee. Fourteen had had an en bloc resection of the distal end of the femur and proximal end of the tibia followed by segmental replacement with a custom-made knee prosthesis and twelve had had an above-the-knee amputation followed by fitting with an artificial limb. Comparisons of free-walking velocity, oxygen consumption per meter traveled, and per cent of maximum aerobic capacity used during walking demonstrated that patients with resection and prosthetic knee replacement had a lower energy cost during gait.
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PMID:Energy cost during gait in osteosarcoma patients after resection and knee replacement and after above-the-knee amputation. 385 67

The uptake of m-[125I]iodobenzylguanidine (mIBG), a compound structurally analogous to the antihypertensive drug guanethidine, was examined in various human cell lines. Of three neuroblastoma lines, SK-N-LO, IMR-32, and SK-N-SH, only the last showed specific uptake of the compound. In contrast, only a nonspecific uptake could be demonstrated for the other neuroblastoma lines, as well as for an osteogenic sarcoma line (SAOS-2) and a melanoma line (IgR 3). Based on analyses of uptake characteristics from Lineweaver-Burk plots it is evident that two different transport mechanisms are responsible for mIBG uptake into SK-N-SH cells: a nonspecific diffusion mechanism, and a specific, active uptake system. The latter was dramatically reduced at 4 degrees compared to 37 degrees, as well as in the presence of ouabain or the absence of oxygen. A competitive inhibition of the transport of mIBG by norepinephrine was observed. When drug-treated SK-N-SH cells were incubated in fresh medium, 20 to 30% of mIBG was still retained in the SK-N-SH cells 24 h after the end of incubation with mIBG, whereas no mIBG was detectable in SK-N-LO cells already after 1 h.
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PMID:Specific uptake of m-[125I]iodobenzylguanidine in the human neuroblastoma cell line SK-N-SH. 386 30

Oxygen remains one of the most potent sensitizers of mammalian cells yet studied and, most important, it is maximumly sensitizing at physiologic concentrations. There is very good evidence that solid tumors of both experimental animals and man contain hypoxic and viable cells. In experimental animals hyperbaric oxygen does result in improvement of radiation therapy even when the treatment is highly fractionated and protracted over periods of up to 3 to 4 1/2 weeks. This represents strong evidence that--at least in some human tumors--results of fractionated irradiation will be significantly improved by the addition of hyperbaric oxygen. At the same time it is admitted that results of clinical trials of hyperbaric oxygen and radiation therapy do not indicate any marked improvement by the addition of hyperbaric oxygen. However, the trials are early and based on small numbers; they may well show a modest but clinically important improvement as they mature. It is essential that the trials cover several tumor types. Hyperbaric oxygen may not be useful in radiotherapy for all tumors. Evidence from the tests of tourniquet hypoxia and radiotherapy indicate that, at least for osteosarcoma, the hypoxic cell per se may not be the dominant factor in deciding results of standard fractionated therapy.
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PMID:Application of radiobiologic principles to radiation therapy. 495 Nov 30

Hypoxia tolerance was measured in female C3H mice which had been given single thoracic X-ray exposures or which were bearing pulmonary tumors. Thoracic X-ray exposures ranging from 500-1500 rad had no significant effect on hypoxic tolerance for up to 56 d following irradiation. The presence of pulmonary tumors from the Dunn osteosarcoma had no significant effect on hypoxic tolerance until a tumor burden of about 200 mm3 was reached. It is concluded that neither a pulmonary radiation history nor moderate lung tumor burdens militate against using reduced oxygen environments in radiotherapeutic regimens to treat pulmonary tumors.
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PMID:Effects of pulmonary x-irradiation and pulmonary tumor burden on hypoxia tolerance of mice. 692 73

It is generally accepted that oxygen has a limited ability to diffuse into solid tumor masses. However, the question of the ability of chemotherapy agents to penetrate solid tumor masses has not been evaluated. This clearly would have an impact on the ability of chemotherapy to control microscopic disease during the "avascular" phase of growth. An attempt was made to evaluate the ability of methotrexate to penetrate solid tumor masses when grown in three dimensions (spheroids). Since methotrexate is used in the clinical management of human osteosarcoma, we chose this drug-tumor combination for our studies. This was done by growing human osteosarcoma cells into spheroids and exposing spheroids of various sizes to tritiated methotrexate. Audioradiographs were obtained from sections through the center of spheroids of various sizes. Our findings suggest that methotrexate has a limited ability to penetrate into avascular tumor masses when grown in three dimensions. This is most evident when the tumor masses are approximately 250 micron and larger in diameter. In addition, we compared the degree of penetration of methotrexate to the growth fraction of the tumor, as measured by tritiated thymidine, and found that the growth fraction was much greater than the fraction of cells reached by methotrexate. We conclude that the limited ability of methotrexate to penetrate solid tumor masses offers an alternative explanation for the limited effectiveness of methotrexate when used as an adjuvant for osteosarcoma. We question whether the established biochemical mechanisms for methotrexate resistance are comprehensive explanations for its limited clinical effectiveness.
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PMID:Limited penetration of methotrexate into human osteosarcoma spheroids as a proposed model for solid tumor resistance to adjuvant chemotherapy. 743 49


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