Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

L-asparaginase (140,000 units) infused into the hepatic artery resulted in a remission from disabling hypoglycaemia for nine months in a man with islet cell carcinoma of the pancreas and hepatic metastases. The tumour produced insulin and gastrin with resulting hypoglycaemia and recurrent peptic ulceration which were unresponsive to other drugs. Following L-asparaginase there was a fall in both plasma and insulin and gastrin.
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PMID:Prolonged control of hypoglycaemia by L-asparaginase in islet cell carcinoma producing insulin and gastrin. 17 39

Antitumor drugs, like any other therapeutic agent, have the ability to incite hypersensitivity reactions. Certain of such drugs (e.g., L-asparaginase and taxol) cause reactions with great enough frequency to be a major impediment to repetitive use of the drug. Very few antitumor drugs have not had at least one reported instance of causing a hypersensitivity reaction. Most reactions are of the type I category in the Gell and Coombs classification, but there also are instances of types II, III, and IV reactions caused by many of the antineoplastic agents. The mechanisms of such reactions have been poorly evaluated in many reports. In analyzing a hypersensitivity reaction in a patient being treated for cancer, one should document that the antitumor drug is indeed the offender, and not an ancillary drug or a formulation product that is being used. There are many tests that evaluate the source and mechanism of hypersensitivity reactions. This article reviews the current information on hypersensitivity reactions to antineoplastic drugs and provides a logical approach for their assessment.
Cancer Metastasis Rev 1987
PMID:Hypersensitivity reactions from antineoplastic agents. 331 75

Radiation is curative in many types of localized cancer, whereas chemotherapy is rarely curative in either localized or widespread cancer. For this reason, chemotherapy should never be employed in any situation where it might hinder or prevent the administration of a potentially curative dose of radiation. However, in Burkitt's tumor in Africa, where a multicentric origin seems to be much more probable, cyclophosphamide, 40 mg/kg intravenously repeated every 3 to 4 weeks, has occasionally been curative. In the treatment of Wilms' tumor, surgery, radiation and chemotherapy are essential for optimal results. In acute leukemia, chemotherapy with the conventional agents, as well as newer drugs such as cytosine arabinoside and L-asparaginase, is the treatment of choice, with radiation being useful mainly in treatment of localized disease in the bones or in the central nervous system. The great interest in L-asparaginase at the present time lies in the fact that certain neoplastic cells have a specific nutritional requirement for the amino acid L-asparagine, whereas no normal cells appear to have this requirement. In many cases of advanced neoplastic disease, the partnership of radiation therapy to reduce large bulky lesions composed to a large extent of nonproliferating cells, followed by chemotherapy to destroy the few surviving and now perhaps proliferating cells remaining in the original mass or in metastases, would seem to offer the greatest promise of theoretical and practical benefit.
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PMID:Chemotherapy and radiotherapy--competitors or partners? 437 33

The tremendous progress that has been made in the chemotherapy of malignant diseases since the early 1950's has enabled the cure of a significant number of cancers such as chloriocarcinoma, Burkitt's lymphoma, Hodgkin's disease, non-Hodgkin's lymphoma, the acute leukaemias, testicular carcinoma, and many childhood cancers such as rhabdomyosarcoma, Wilm's tumor, Ewing's sarcoma, ovarian cancer, and retinoblastoma. As a result, the mortality from cancers has dropped by 15% for persons under the age of 45 years and even more for those under 30 years of age. Many other metastatic cancers can now be successfully controlled with chemotherapy and, ultimately, more will be added to the growing list of curable cancers. The chemotherapeutic agents responsible for the cures of some cancers include asparaginase, actinomycin D, Adriamycin, bleomycin, cisplatin, cyclophosphamide, cytosine arabinoside, 5-fluorouracil, 6-mercaptopurine, methotrexate, nitrogen mustard, prednisone, procarbazine, and vincristine. The discovery of new effective drugs such as AMSA and anthracenedione promises to improve the success rates obtained with present therapy. Chemotherapy is indicated for every patient who has metastatic cancer, since virtually every patient can receive some palliation from such therapy, while for some patients chemotherapy holds the promise of prolongation of life or even cure.
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PMID:The curability of advanced cancers with chemotherapy. 627 28

An extra-corporeal chamber has been constructed and used for diagnosis, enzyme therapy and immuno-adsorption. The chamber is made from polymethyl-acrylate and the dimensions of the chamber are 10 x 18 x 7 cm. It contains 23 plates with a total area of 0.5 m2. In most cases no pump is used. The active substance is bound covalently to the plate surfaces. The time for each hemoperfusion has been 3-6 hr. No infections, decrease of thrombocytes or other side effects have been observed. By immobilized homologous antisera (F (ab')2), three putative tumour-associated antigens were isolated from cases of hypernephroma. Two children and one adult patient with malignant lymphoma were treated with extra-corporeal L-asparaginase, the latter with repeated remissions of metastases. The level of antibodies against Factor VIII was significantly decreased by chamber immunoadsorption in two cases of hemophilia. A number of kidney transplantation cases received extra-corporeal L-asparaginase pre- and post-operatively to counteract rejection. In all around 50 patients have received extra-corporeal treatment without any adverse effects. The use of the extra-corporeal chamber in other diseases is discussed.
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PMID:Enzyme therapy and immuno-adsorption by an extra-corporeal device. 698 19

Clinical pharmacology of L-asparaginase was compared by intramuscular and intravenous injections in 12 patients with metastatic cancer or leukemia. Following a single intramuscular injection at the gluteal site of L-asparaginase (10,000 IU/m2), the enzyme appeared in plasma as measured initially at 1 hour, but plateau levels were not reached in plasma until 14 to 24 hours after drug administration. The peak plasma level was 1.12 IU/ml, only one fourth of that seen when L-asparaginase was given intravenously at equal doses. However, the enzyme level decrease in the plasma after intramuscular injections was slower, with a half-life ot 46 hours, compared to 7 to 28 hours for intravenously administered drug. The apparent volume of distribution indicated that the intravenously injected enzyme was mostly distributed in plasma, whereas the intramuscularly injected enzyme yielded a much larger volume of distribution (63 versus 245 ml/kg). In addition, only 19 per cent of the intramuscularly injected dose was in plasma, and the area under the curve (C X t) was only 1/24 that by intravenous route (20 versus 487 IU/ml.hr). No enzyme was measurable in patients' urine samples collected for three days after intramuscular injections of the enzyme, and only a trace (less than 1 per cent) of the enzyme was detected in urine after intravenous administration.
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PMID:Clinical pharmacology of intramuscularly administered L-asparaginase. 722 20

Using a functional model of breast cancer heterogeneity, we previously showed that clonal sub-populations proficient at generating circulating tumour cells were not all equally capable of forming metastases at secondary sites. A combination of differential expression and focused in vitro and in vivo RNA interference screens revealed candidate drivers of metastasis that discriminated metastatic clones. Among these, asparagine synthetase expression in a patient's primary tumour was most strongly correlated with later metastatic relapse. Here we show that asparagine bioavailability strongly influences metastatic potential. Limiting asparagine by knockdown of asparagine synthetase, treatment with l-asparaginase, or dietary asparagine restriction reduces metastasis without affecting growth of the primary tumour, whereas increased dietary asparagine or enforced asparagine synthetase expression promotes metastatic progression. Altering asparagine availability in vitro strongly influences invasive potential, which is correlated with an effect on proteins that promote the epithelial-to-mesenchymal transition. This provides at least one potential mechanism for how the bioavailability of a single amino acid could regulate metastatic progression.
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PMID:Asparagine bioavailability governs metastasis in a model of breast cancer. 2971 30