Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Trewiasine (TWS) is a mytansinoid compound. It possessed a significant cytotoxic activity against various human cancer cell lines in vitro. U937 cells, which were more sensitive to the TWS, required TWS 1 microgram.ml-1 to inhibit cell growth over 90% (P less than 0.01). TWS also showed activities against murine tumors in vivo, such as the ascitic tumors S180, hepatoma, U14, and solid tumor Lewis lung carcinoma. Depression of leukocytes was not seen when mice were given ip TWS 10 or 50 micrograms.kg-1.d-1 x 7 d. TWS 0.1-1 micrograms.ml-1 caused no sister chromatid exchange induction in Chinese hamster cell line V79.
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PMID:Cytotoxic activity of trewiasine in 4 human cancer cell lines and 5 murine tumors. 144 9

Acivicin (AT-125) is a glutamine antagonist with dose-limiting, schedule-dependent CNS toxicity and predictable CSF penetration after intravenous administration. Because of these properties, a trial in CNS malignancies was initiated. Thirty-two patients with recurrent or residual malignant astrocytomas were treated with AT-125. The majority of patients had glioblastoma multiforme (24) and had received prior nitrosoureas (21). The median age was 50 years, and Southwest Oncology Group (SWOG) performance status was 2. The major determinant of response was based upon radiologic criteria using computed tomographic (CT) scanning and/or magnetic resonance imaging (MRI) scans. The tumor mass was measured in two perpendicular planes, which yielded the largest cross-sectional area. Standard solid tumor criteria for response were used. All responding patients also had a stable or tapered dose of corticosteroids with stable or improved performance status and neurologic examination. There were four objective responses (12%): one complete remission (3 1/2+ years) and three partial remissions (57, 86, and 322 days). Two patients had improvement in disease that did not meet requirements for a partial remission. Toxicity was mild and primarily consisted of nausea, vomiting, and lethargy. Two patients were removed from study due to neurotoxicity (depression and hallucinations). The strict response criteria used in this trial were not those that have been used in testing other active agents such as carmustine (BCNU). We conclude that AT-125 has objective antitumor activity in malignant astrocytomas and warrants further study.
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PMID:Objective antitumor activity of acivicin in patients with recurrent CNS malignancies: a Southwest Oncology Group trial. 164 69

ICRF-187 is the (+) enantiomer of the racemic mixture razoxane (ICRF-159). This compound is much more water soluble and thus could be formulated for parental use. The maximum tolerated dose in children after phase I trials was determined to be 3500 mg/M2/day x 3 days. A phase II trial of ICRF-187 was done in 21 children with solid tumors and 35 children with acute leukemia. All these patients were less than 21 years of age, had recovered from previous chemotherapy, had normal liver and kidney functions, and had a life expectancy of greater than 4 weeks. ICRF-187 was administered at a dose of 3 g/M2/day for 3 days as a 4 hour infusion each day. In patients with leukemia, no objective response was seen in the bone marrow although a few patients had a decrease in peripheral blast count. There were no measurable responses seen in patients with a solid tumor. ICRF-187 was well tolerated. The major toxicity was hematopoietic depression. Significant but rare toxicities included moderate to severe nausea and vomiting, and elevation of bilirubin and transaminases. Although inactive in the current study, ICRF-187 might be more active in another schedule.
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PMID:Phase II trial of ICRF-187 in children with solid tumors and acute leukemia. 180 8

The effect of a reticuloendothelial blockade was examined on the tissue distribution of 99mTc-labeled synthetic liposomes prepared from N,N-didodecyl-N alpha-[6-(trimethylammonio)hexanoyl]-L-alaninamide bromide (N+C5Ala2C12) in Ehrlich solid tumor-bearing mice. While a pre-dose of unlabeled phosphatidyl choline liposomes (natural liposomes) hardly influenced the tissue distribution of N+C5Ala2C12 liposomes, the pretreatment of dextran sulfate depressed the uptake in liver accompanied by increasing that in tumor and other tissues except the stomach. However, the extent of liver depression of N+C5Ala2C12 liposomes by dextran sulfate was lower than that of natural liposomes and the pre-dose of unlabeled natural liposomes had a minor effect on the tissue distribution of N+C5Ala2C12 liposomes compared with that of natural liposomes. In the liver uptake of N+C5Ala2C12 liposomes, it was suggested that Kupffer cell phagocytosis was not the main mechanism.
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PMID:Effect of reticuloendothelial blockade on tissue distribution of 99mTc-labeled synthetic liposomes in Ehrlich solid tumor-bearing mice. 204 8

The immune function of patients with hairy cell leukemia (HCL) and solid tumors was evaluated before and after treatment with the investigational drug 2'-deoxycoformycin (pentostatin; dCF). Thirteen HCL patients received doses of dCF of 2 to 4 mg/m2 intravenously at 2- to 6-week intervals for up to 15 courses. After completion of treatment, 12 of 13 patients had resolution of severe monocytopenia and five of nine had normal monocyte antibody dependent cellular cytotoxicity. There was statistically significant depression of total lymphocytes, T cells, and B cells. Evaluation of T subsets showed a decrease in CD4+ cells. Immunoglobulin G (IgG) in sera were decreased from baseline, while IgM and IgA were unaffected. There was no significant effect on skin-test reactivity or large granular lymphocyte numbers. Lymphoblastic transformation was variably affected. Natural-killer (NK) cell function was improved or unchanged after dCF treatment. Reevaluation of seven patients at 21 to 119 weeks after receiving dCF demonstrated that recovery to normal T- and B-cell numbers and subsets does occur. Five solid tumor patients were given dCF at 4 mg/m2 intravenously at 1- to 2-week intervals for up to five courses. There was significant reduction in T cells, B cells, CD4+, and CD8+ cells with no statistically significant effect on the other immune parameters. We conclude that low doses of dCF can cause persistent immunosuppression though recovery may occur after the drug is stopped. In patients followed after completion of dCF, there was no associated increase in second malignancies or unusual infections.
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PMID:Immunosuppressive effects of pentostatin. 233 71

Inbred 'Strain 2' guinea pigs bearing an intradermally growing and already lymphogenetically metastasized solid tumor ('Line 10') were successfully treated by multiple intralesional chemotherapy. The animals developed tumor-specific immunity. Depression of T lymphocyte function abolished the curative effect of this therapy. After treatment with antilymphocyte serum or cyclosporin A all animals receiving intratumoral chemotherapy with cisplatinum or low-dose vincristine showed progressive tumor growth. Immunosuppression with antilymphocyte serum or cyclosporin A did not interfere with high-dose vincristine treatment.
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PMID:Animal experiments on the role of T lymphocytes in the course of antineoplastic chemotherapy. II. Chemotherapy and T lymphocyte depression. 349 72

Correlation between antitumor activity and effects on some biological properties, such as phagocytic activity of the reticuloendothelial system, the third component of complement (C3) activation, hepatic drug-metabolizing activities and pentobarbital-induced narcosis, of antitumor agents from various natural sources such as B B (Broncasma Berna), GU-P (Grifora umbellata polysaccharide), OK-432, PS-K (Polysaccharide Kureha), and RA-P (Rumex acetosa polysaccharide) were studied with female ICR mice implanted with Sarcoma 180 solid tumor. All of these agents depressed aniline hydroxylase and aminopyrine demethylase activities, prolonged the duration of pentobarbital-induced narcosis, and significantly enhanced the phagocytic activity and C3 activity. Especially, RA-P which has the strongest antitumor activity was the most effective in changing these activities. The biological activities of GU-P at a dose of 10 mg/kg reached the same level as that found with PS-K at a dose of 100 mg/kg. a possible mechanism of inhibition of Sarcoma 180 solid tumor growth by the treatment with the antitumor agents could be interpreted as due to the C3 activation, the stimulation of phagocytic activity and depression of the hepatic microsomal drug-metabolizing system in tumor-bearing mice.
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PMID:Effects of the antitumor agents from various natural sources on drug-metabolizing system, phagocytic activity and complement system in sarcoma 180-bearing mice. 371 70

A case of male cystic prolactinoma is reported. And six cases of male prolactinoma including the present case were experienced in our department, and they were studied clinically. A 40-year-old male was admitted to our hospital with complaints of decreased libido and bitemporal visual depression. Physical examination revealed neither gynecomastia nor galactorrhea. Decreased visual acuity, bitemporal hemianopia, and pale optic disc were disclosed. On endocrinological study, high serum level of prolactin and hyposecretion of the other pituitary hormones were shown. Plain skull x-ray films showed ballooning of the sella turcica. CT scan revealed a low density area in the pituitary fossa extending to the suprasellar region. This was visualized as a homogeneous high signal intensity in the T1 weighted magnetic resonance imaging. Surgical treatment was made by transsphenoidal approach. A considerable amount of dark reddish fluid was suctioned through an incision of the thinned dura mater. Postoperative course was uneventful, and the bitemporal hemianopia was much improved. The serum level of prolactin was normalized after administration of bromocriptine. Male prolactinomas were thought to constitute 20% of all prolactinomas and male cystic prolactinoma was a rare clinical entity. Since the serum level of prolactin became to be measured routinely, six male prolactinomas have been experienced in our department. Their clinical feature were summarized as follows; Mean age of the patients was 33.2 +/- 9.8 years. Marked suprasellar extension and associated visual disturbance were common. All lesions except in the present case were solid tumor. Mean serum level of prolactin was 3398.3 +/- 2758.4 ng/ml. Pituitary apoplexy during the test of insulin, TRH and LH-RH simultaneous loading was noted in two cases.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[A case of male cystic pituitary adenoma with hyperprolactinemia--clinical study of 6 cases of male prolactinoma]. 382 60

A 64-year-old female visited Kawatetsu Chiba Hospital complaining of left retro-orbital pain. A month before, she had experienced ptosis and diplopia, that had been releaved two days later by corticosteroid. On admission, she had no neurological deficits except for minimal anisocoria, with the left pupil larger than the right. There was no cutaneous manifestation of von Recklinghausen's disease. Skull X-ray films showed depression of the floor of the sella turcica on the left side. CT scans demonstrated a parasellar enhancing mass with intrasellar extension. Left carotid angiogram showed intracavernous portion of the internal carotid artery displaced laterally, inferiorly, and anteriorly. With a tentative diagnosis of laterally extending pituitary adenoma, a transsphenoidal operation was carried out, which disclosed a solid tumor locating beside the medially-displaced pituitary gland. The histological diagnosis was typical neurinoma. Parasellar neurinoma is not so common. It is usually difficult to determine the origin of the parasellar neurinoma. Trigeminal neurinoma arising from the Gasserian ganglion is generally recognized to be the most frequent. However, the absence of the trigeminal nerve involvement, unusual CT findings, and angiographical changes in the present case were all different from those of the typical trigeminal neurinoma. We believe that the tumor of this case originated from the oculomotor nerve. Fifteen cases of neurinoma of the oculomotor, trochlear, and abducens nerve have been reported to date. Their clinical features were reviewed.
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PMID:[Neurinoma with intrasellar extension: a case report]. 398 98

Trimetrexate is a novel lipophilic folate antagonist that causes growth inhibition, inhibition of nucleic acid biosynthesis, and cytotoxicity at nanomolar concentrations in tissue cultures. The potency of trimetrexate cytotoxicity against most cell lines is greater than that of methotrexate. Trimetrexate has antitumor activity in vivo in several murine leukemia and solid tumor systems, including tumors in which methotrexate is inactive. Antitumor activity was seen following oral, intravenous, or intraperitoneal administration. Trimetrexate causes a pronounced and early depression in incorporation of deoxyuridine into DNA. In tumor cell lines resistant to methotrexate because of a drug transport defect, trimetrexate retains activity. In many such cases the methotrexate-resistant tumors show collateral sensitivity to trimetrexate. In methotrexate-resistant cells with impaired drug transport, trimetrexate sensitivity was even more pronounced when cells were grown in folate-free medium supplemented with physiological levels of tetrahydrofolate cofactor. In the human tumor stem cell colony assay, trimetrexate, at concentrations achievable in vivo, gave activity against many human tumors, including samples that were unresponsive to methotrexate. Trimetrexate crosses the blood-brain barrier, and at very high doses may cause neurotoxicity. At conventional doses the primary toxic effects in mice are gastrointestinal. This toxicity is reversible at therapeutic doses. Unlike earlier lipophilic antifolates, trimetrexate has rapid plasma clearance (t1/2 in mice of 45 minutes). Trimetrexate is a tight-binding competitive inhibitor of dihydrofolate reductase. The Ki,slope for inhibition of the human enzyme was 4 X 10(-11) M. A dose-dependent decrease in cellular purine ribonucleotide pools is given by trimetrexate. Pyrimidine ribonucleotide pools tend to increase in treated cells. Trimetrexate caused a marked depression of cellular pools of dTTP and dGTP, and a lesser depression in dATP. Cytotoxicity of trimetrexate in vitro was prevented by leucovorin. Leucovorin also protected mice from trimetrexate toxicity. Thymidine protected cells from lethal effects of low concentrations of trimetrexate, but not from high concentrations. The combination of thymidine and hypoxanthine completely protected cells from low and high concentrations of trimetrexate. A new, stable and highly water-soluble formulation of trimetrexate has been developed. Because of the interesting biochemical and pharmacological properties of trimetrexate, and its experimental antitumor activity, clinical trials are planned.
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PMID:Biochemical pharmacology of the lipophilic antifolate, trimetrexate. 623 75


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