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At least 19 recordsLinked to original sources

A longitudinal study of patients with superficial bladder carcinoma successfully treated with weekly intravesical thio-tepa.

Herein is reported further results of a prospective clinical investigation to determine the effect of weekly intravesical bladder instillation of thio-tepa in the treatment of superficial bladder cancer. Patients with superficial bladder carcinoma were treated according to 2 protocols. The first protocol consisted of patients with persistent tumor who were treated with weekly thio-tepa for 8 weeks. Of the 33 patients 18 responded to this therapy, and they and 24 other patients who had been rendered free of tumor by transurethral resection alone were assigned to the second protocol in which patients either were treated with monthly instillations of thio-tepa or they were observed every 3 months in a prescribed fashion. Monthly thio-tepa instillations had no significant effect in lowering the recurrence rate in either group. However, in the patients who had responded to weekly thio-tepa benefit was noted in terms of 1) fewer recurrences, with 8 of 18 (44 per cent) previously pre-treated patients having a recurrence versus 19 of 24 patients (79 per cent) previously untreated, 2) delay in tumor recurrence with an interval free of tumor of 15.1 months in pre-treated patients versus 4.3 months in the untreated group and 3) diminished frequency of new tumors (0.33 recurrences yearly) in comparison to the untreated group (1.78 recurrences yearly). The remaining patients are free of tumors at 15.7 months average followup.

Carcinoma, Transitional Cell↗

Morphologic effects of thio-TEPA on mammalian urothelium. Changes in abnormal cells.

Morphologic changes induced by thio-TEPA were examined in animals with chemically induced neoplasms. Both toxic and metabolic effects were documented. Degeneration, vacuolization and increased exfoliation (toxic) were most prominent, occurred within 48 hours of exposure, and tended to subside after removal of the drug. Nuclear changes (metabolic) were rare and occurred late. Neither toxic nor metabolic effects were specific for thio-TEPA: both could be detected in control animals receiving saline. The metabolic effects of thio-TEPA are not sufficiently widespread to prevent tumor growth.

Animals↗

The effect of fractionated exposure to thio-TEPA upon Chinese hamster cells in vitro.

The dependence of the surviving fraction of Chinese hamster cells in vitro upon the concentration of Thio-TEPA, upon the duration of drug exposure and upon fractionation of drug exposure has been studied. Given a constant exposure time, the surviving fraction decreased according to a "shoulder" curve with increasing concentration. Given a constant concentration, the surviving fraction decreased exponentially with increasing exposure time. Splitting exposure of 60 min into two 30 minutes' exposures with drug-free intervals of several hours increased the cytostatic effect of Thio-TEPA.

Animals↗

Intravesical thio-tepa in the immediate postoperative period in patients with recurrent transitional cell carcinoma of the bladder.

Recurrent transitional cell carcinoma was treated with prophylactic intravesical thio-tepa in 22 cases. Group 1 patients were treated with 30 mg. twice daily for the first 3 days postoperatively. Group 2 patients were given additional treatment at increasing intervals indefinitely. Before therapy control patients averaged 1 recurrence every 9.5 months. Group 1 patients averaged 1 recurrence per 33 mpnths. Group 2 patients averaged 1 recurrence per 41 months. Leukopenia occurred in only 2 patients. Thio-tepa can be given safely in the immediate postoperative period and is effective in decreasing the recurrence rate of superficial bladder tumors.

Adolescent↗

Intravesical thio-tepa: a study of 3H-thymidine uptake in normal urothelium and FANFT-induced tumors in rats.

Treatment of superficial low-grade bladder cancer often incorporates intravesical instillations of the alkylating agent thio-TEPA. Current dosages and administration schedules are empiric inasmuch as cytokinetic data are sparse. The FANFT-induced bladder rat tumor model closely approximates human bladder cancer. This study measuring 3H-thymidine uptake identified peaks of maximal synthetic activity at 3 and 9 days after thio-TEPA exposure in both normal and neoplastic urothelium. Thus, repeat instillation at these intervals may improve cytotoxicity and overall response rate.

Animals↗

Local application of THIO-TEPA in the prevention of recurrent papillary carcinoma of the bladder.

Prophylactic total THIO-TEPA treatment was employed in 44 cases over a period of five years, following radical surgery (including reoperations) for recurrent vesical papillomatosis or carcinoma, and numerous subsequent transurethral coagulations or resections owing to multiple recurrences. Three patients have been now free from recurrences for five years, 13 patients for four years, 11 patients for three years and 9 patients for two years. Eight patients proved unresponsive, the recurrence rate having remained unaffected. No toxic effects requiring any special measures were encountered.

Administration, Topical↗

The apparent decrease in thiotepa-induced chromosome aberrations in human lymphocytes caused by an effect of WR2721 on the cell cycle as found by the definitively determined division method.

Antimutagenic radioprotective compounds have been reported to decrease the yield of chemically induced chromosome aberrations even when administered long before the chemical mutagen thio-TEPA. Because thio-TEPA can induce aberrations in all parts of the cell cycle, it seemed likely that the apparent decrease in aberrations was the result of an effect of the antimutagen on the progression of cells through the cell cycle so that cells treated in the more sensitive stage would be scored. To test this possibility human lymphocytes were treated with the protective compound WR2721 and then thio-TEPA. The cells were grown in the presence of 5-bromodeoxyuridine, which allows the definitive determination of metaphases from cells that divided once, twice, or three times after treatment. The yield of aberrations observed in first division cells was the same whether or not the protector was present. A decrease in aberration yields appeared only in rapidly cycling cells that were in the second division at the time of fixation. Labeling experiments showed that in this rapidly dividing population fewer of the metaphase cells had been in G2 when thio-TEPA was added. The results indicate that part of the decrease in aberration yields obtained by treatment with an antimutagen several hours before the addition of a mutagen is an artifact of cell selection.

Amifostine↗

Factors related to survival following resection for gastric carcinoma: analysis of 903 cases.

This report is based on 903 patients with resections for gastric carcinoma between October 1957, and July 1969, entered in controlled trials of adjuvant therapy with Thio-TEPA and FUDR. Neither Thio-TEPA nor FUDR, as administered, prolonged survival. The extent of disease at the time of curative surgery is related to survival for the first 36 months postoperatively. Involvement of lymph nodes, resection of the esophagus, and serosal penetration are predictive of recurrence up to 36 months. There appear to be three groups of patients: 1) Cured (26%); 2) Slowly growing tumor--23% (median survival, 25 months); and 3) Rapidly growing tumor--51% (median survival, eight months). The absence of blood-vessel invasion, lymphatic invasion, lymph-node involvement, and serosal penetration characterize those patients in Group A.

Adult↗

The mutagenic activity of anti-cancer drugs and the urine of rats given these drugs.

Twenty-one anti-cancer drugs have been tested for their ability to cause mutations in Salmonella typhimurium test strains in the Salmonella/microsome mutagenicity test. Nine of the 21 anticancer drugs showed this ability: cyclophosphmide, nitromin, thio-tepa, busulfan, 6-mercaptopurine, neocarzinostatin, daunomycin, adriamycin and estramustine phosphate. Seven of these 9 mutagenic drugs were injected continuously into the jugular veins of rats. Urine was collected through a cystostomy tube and tested for mutagenicity. The urine from rats treated with 6 of these 7 drugs was mutagenic. These were cyclophosphamide, nitromin, thio-tepa, neocarzinostatin, adriamycin and daunomycin.

Alkylating Agents↗

Histopathology and histochemistry of the insects treated with chemosterilants VI: brain damage including reduced neurosecretion caused by chemosterilants in Periplaneta americana (L).

The brain is damaged and neurosecretion is reduced in the P. americana treated with chemosterilants thio-tepa and bis (dimethylamino) dithiazolium chloride. The damage includes, separation of neurolemma, vacuolisation and chromatolysis in the nuclei of neurons and extensive damage to fibres. Reduced neurosecretion, vacuolisation in the cytoplasm and karyolysis in the nucleus of neurosecretory cells, are also observed. These changes in the brain are of considerable importance to understand the mode of action of the chemosterilants.

Animals↗

Mutagenicity tests with griseofulvin.

Griseofulvin was studied for its ability to induce structural chromosomal aberrations in germ and somatic cells of the male mouse. It was also tested for its capacity to produce his+ revertants in Salmonella typhimurium. All tests yielded negative results, whereas highly significant effects were recorded in control assays with thio-TEPA.

Animals↗

Effects of cancer chemotherapeutic agents on testicular DNA synthesis in the rat. Evaluation of a short-term test for studies of the genetic toxicity of chemicals and drugs in vivo.

Changes in the rate of testicular DNA synthesis in the rat were studied at various times after single doses of 12 cancer chemotherapeutic agents. The animals were given intravenous injections of [14C]thymidine and [3H]thymidine 24 and 3 h, resp., before they were killed. By combining measurements of the free serum radioactivity and the testicular incorporation of the differentially labelled precursor, different response patterns were obtained for agents with different modes of action. The DNA-damaging agents cyclophosphamide, chlorambucil, thio-TEPA, busulphan, CCNU and procarbacine, after some delay, caused a decrease of testicular thymidine incorporation and a corresponding increase of free serum radioactivity. The non-DNA-damaging agents 5-fluorouracil, methotrexate, hydroxyurea and cytosine arabinoside had a rapid effect on testicular thymidine incorporation and produced diverse response patterns different from that of the DNA-damaging agents. Actinomycin D and also vinblastine caused changes in testicular thymidine incorporation and showed response patterns different from those of the other agents. These results show that simple measurements of testicular DNA synthesis may provide useful information for the evaluation of genotoxic effects of chemical compounds and may help one to distinguish between DNA-damaging agents and metabolic inhibitors of DNA synthesis.

Animals↗

[Effect of age on the sensitivity of mouse spermatogonia to mutagenic action].

Male BALB/c mice were whole body exposed to 0, 100, 200 or 300 R of X-rays or were given an i.p. injection of 5 mg/kg of thio-TEPA at 3 months or at 12 months of age. One hundred days after treatment the testes were examined for the presence of reciprocal translocations induced in spermatogonia and detectable in the dividing spermatocytes. Our results show that ages does not influence the yield of scorable chromosome rearrangements.

Aging↗

Mutagenicity of cancer chemotherapeutic agents in the Salmonella/microsome test.

Seventeen cancer chemotherapeutic agents were tested for their ability to mutate Salmonella typhimurium tester strains in the Salmonella/microsome mutagenicity test. There was a high correlation between the mutagenicity and carcinogenicity of a given agent. Carcinogens positive in the test were Adriamycin, daunomycin, 1-propanol-3,3'-iminodimethanesulfonate, cyclophosphamide, isophosphamide, hycanthone, chlornaphazin, nitrogen mustard, uracil mustard, melphalan, and thio-tepa. Two carcinogesn, actinomycin D and bleomycin, were not detected as mutagens. The presumptive noncarcinogen, methotrexate, was negative in the test. Tilorone and 6-mercaptopurine, tentatively classified as noncarcinogens, were mutagenic. The carcinogenicity of cis-dichlorodiammineplatinum(II), which was positive in the test, has not been determined.

2-Naphthylamine↗