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At least 991 records · Page 55Linked to original sources
PubMed1979

[Risk of a second malignant neoplasm after successful treatment of a malignant tumour in children (author's transl)].

One boy, given radiotherapy and cytostatic drugs for a rhabdomyosarcoma died nine years later of acute leukaemia. A girl, who had received radiotherapy for an inoperable suprasellar tumour and also given cytostatic drugs, fell ill seven years later with a glioblastoma. Among a total of 750 children with malignant neoplasm observed by the authors, a permanent cure rate of about 50% is to be expected among about 300 children treated recently. If this rate applies to the entire Federal Republic of Germany, about 1,000 children are likely to be cured annually. In these circumstances it is likely that 80-160 children treated in any one year will develop a second neoplasm or leukaemia 20 years later, most commonly as a late sequela of the treatment.

Adolescent↗
PubMed2000

Venoocclusive liver disease (VOD) as a complication of Wilms' tumour management in the series of consecutive 206 patients.

UNLABELLED: In 4 years (1993-1996) 206 pts. with nephroblastoma were treated. All children were treated according to SIOP 93-01 protocol. Overall survival was 92%. In 27 cases hepatotoxic events occurred. In 10 cases, venoocclusive liver disease (VOD) was diagnosed. VOD is a syndrome associated with hepatomegaly, sudden weight gain or ascites and jaundice. It results from damage to the endothelium of hepatic venules and necrosis of central hepatocytes with subsequent proliferation of fibrous tissue and occlusion of the central hepatic veins. Dactinomycin is one of the drugs considered responsible for its development. Mean age of VOD patients was 4 yrs, however 3 of them were below 1 yr. In all cases, VOD occurred during postoperative chemotherapy (mean 16 th week of treatment). All patients received dactinomycin and vincristine. Five children with right kidney tumors underwent post-operative abdominal irradiation. Main VOD symptoms were hepatomegaly and ascites (80%). Hypertransaminasaemia, as well as, on ultrasound, gallbladder wall thickening and/or free abdominal fluid were observed. Median VOD duration was 27 days and its course was usually temporary and self-limiting. However, in 2 cases recurrent VOD episodes were noted. All children received supportive treatment only. In 6 cases, VOD resulted in chemotherapy delay or drug reductions, while in 4 others chemotherapy was completed preliminarily. Nevertheless it did not affect patients' outcome overall survival in VOD group was 90%. CONCLUSIONS: Total 5% VOD frequency is similar to other reports. Infants and children receiving abdominal irradiation seem to be at special risk of VOD development.

Adolescent↗
PubMed1990

Depletion of mammalian O6-alkylguanine-DNA alkyltransferase activity by O6-benzylguanine provides a means to evaluate the role of this protein in protection against carcinogenic and therapeutic alkylating agents.

O6-Alkylguanine-DNA alkyltransferase was rapidly and irreversibly inactivated by exposure to O6-benzylguanine or the p-chlorobenzyl and p-methylbenzyl analogues. This inactivation was much more rapid than with O6-methylguanine: incubation with 2.5 microM O6-benzylguanine led to more than a 90% loss of activity within 10 min, whereas 0.2 mM O6-methylguanine for 60 min was required for the same reduction. O6-Benzylguanine was highly effective in depleting the alkyltransferase activity of cultured human colon tumor (HT29) cells. Complete loss of activity was produced within 15 min after addition of O6-benzylguanine to the culture medium and a maximal effect was obtained with 5 microM. In contrast, at least 100 microM O6-methylguanine for 4 hr was needed to get a maximal effect, and this reduced the alkyltransferase by only 80%. Pretreatment of HT29 cells with 10 microM O6-benzylguanine for 2 hr led to a dramatic increase in the cytotoxicity produced by the chemotherapeutic agents 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) or 2-chloroethyl(methysulfonyl)methanesulfonate (Clomesone). Administration of O6-benzylguanine to mice at a dose of 10 mg/kg reduced alkyltransferase levels by more than 95% in both liver and kidney. These results indicate that depletion of the alkyltransferase by O6-benzylguanine may be used to investigate the role of the DNA repair protein in carcinogenesis and mutagenesis and that this treatment may be valuable to increase the chemotherapeutic effectiveness of chloroethylating agents.

Antineoplastic Agents↗
PubMed1978

Chemotherapy for lung cancer.

Oat cell carcinoma is the one variety of primary lung cancer which is sufficiently responsive to a variety of drugs and drug combinations that a very high rate of response and significant prolongation of survival can be consistently achieved. The question of whether anyone has been "cured" by drug treatment awaits more study and the passage of time. Progress in the treatment of the other varieties of bronchogenic carcinoma is less encouraging. There is only the hope that more fundamental knowledge about the nature of the disease will bring greater progress.

Bleomycin↗
PubMed1998

Chemotherapy for aggressive or anaplastic high grade oligodendrogliomas and oligoastrocytomas: better than a salvage treatment.

This series reports a pilot study of chemotherapy conducted for newly diagnosed and relapsing patients with oligodendrogliomas and oligoastrocytomas. Twenty-three patients with clinically or histologically aggressive tumours were eligible to receive procarbazine CCNU and vincristine (PCV) chemotherapy followed by radiotherapy in previously non irradiated patients. Sixteen (69%) responded to chemotherapy with complete responses in two patients and partial responses in 14. Previously irradiated patients were as likely to respond to PCV as those previously non irradiated. An over 1-year history of seizures was the main clinical prognostic factor of response. All toxicities were manageable and no treatment related deaths occurred. Chemotherapy is an effective treatment in aggressive oligodendrogliomas. Further studies must assess the role of chemotherapy in the multidisciplinary management of oligodendroglioma.

Adolescent↗
PubMed2003

Long-term sequelae in children treated for brain tumors: impairments, disability, and handicap.

Sixty-one long-term survivors, treated for brain tumors in childhood, were evaluated in term of neurological impairments, disability, and handicap. Thirty-eight patients (pts) (62%) had at least one impairment. Visual impairment was detected in 14 pts (24%), associated with recurrence (p = .012). Thirty-four patients (56%) had motor impairment, associated with sex (female) in irradiated patients; 13 (21%) had epilepsy, associated with supratentorial tumor site (p = .001). The same number of patients had brain atrophy; risk factors were hydrocephalus at diagnosis and perioperative complications. Sixteen patients (30%) had IQ score < 80, associated with young age at first treatment (p = .006) and recurrence (p = .043). Twenty-seven out of 61 of our patients (44%) were disabled: 12 mildly, 14 moderately, and 1 severely. Epilepsy was the most important risk factor for disability. Cognitive impairment, motor impairment, and epilepsy were associated with employment (43%); cognitive impairment was also associated with education.

Adolescent↗
PubMed1987

Enhancement of misonidazole chemopotentiation by mild hyperthermia (41 degrees C) in vitro and selective enhancement in vivo.

Experiments were designed to test the hypothesis that mild heat treatment would selectively increase misonidazole (MISO) chemopotentiation of CCNU toxicity in hypoxic versus aerobic cells in vitro and in tumours in vivo via an augmentation of nitroreduction. EMT-6 cells were exposed to CCNU +/- 1.0 mM MISO under aerobic or hypoxic conditions for 4 h either at a constant 37 degrees C or at 41 degrees C for the first hour followed by 37 degrees C for the remaining 3 h. Chemopotentiation was not observed under aerobic conditions and heat treatment did not modify CCNU toxicity. Co-incubation with MISO and CCNU under hypoxic conditions resulted in enhanced toxicity (i.e. chemopotentiation) with either incubation protocol; however, the magnitude of the enhancement was significantly larger (P less than 0.025) when 41 degrees C incubation was included. Systemic heat treatment produced a similar enhancement of chemopotentiation in KHT tumours in C3H/HeN mice treated with MISO (0.5 mg g-1) and whole body hyperthermia (41 degrees C, 1 h) prior to administration of CCNU (15 mg kg-1). Heating had no effect on CCNU response but doubled the median growth delay produced by the CCNU-MISO combination. Heat treatment did not enhance myelosuppression of the combination. Both the in vitro and in vivo data indicate that mild hyperthermia can selectively enhance the magnitude of MISO chemopotentiation.

Aerobiosis↗
PubMed1992

Advantage of post-radiotherapy chemotherapy with CCNU, procarbazine, and vincristine (mPCV) over chemotherapy with VM-26 and CCNU for malignant gliomas.

Between 1981 and 1987, 133 patients with anaplastic astrocytoma (AA) or glioblastoma multiforme (GBM) were treated with surgery and post-operative radiotherapy. 36 AA and 31 GBM patients were treated with adjuvant chemotherapy consisting of CCNU 100 mg/m2 day 1, procarbazine 60 mg/m2 days 1-14, and vincristine 1.4 mg/m2 (max. 2 mg) days 1 and 8, every 6 weeks which we called a "modified PCV" (mPCV) regimen. 37 AA and 29 GBM patients were treated with adjuvant chemotherapy consisting of VM-26 75 mg/m2 days 1 and 2, and CCNU 60 mg/m2 days 3 and 4, every 6 weeks. Prognostic covariates such as patient's age, Karnofsky performance status score and the extent of surgery were balanced between the two treatment groups. The time to tumor progression and survival time for both regimens show that mPCV produces a two-fold increase in these factors at the 50th and 25th percentile for AA patients, but not for GBM patients, although there are more long-term GBM survivors with mPCV than with the VM-26 + CCNU regimen.

Adult↗
PubMed1985

Hepatic arterial and systemic chemotherapy for the treatment of primary and secondary malignancies of the liver.

Twenty-two patients with metastatic and primary cancer of the liver were treated with 5-fluoro-2'-deoxyuridine (5FUDR), Mitomycin C (Mito C), and 1 (-2-chlorethyl)-4(methyl-cyclohexyl)-1-nitrosourea (MeCCNU). 5FUDR 0.3 mg/kg/day was administered as a continuous infusion via the hepatic artery. Mito C (10 mg/M2) and MeCCNU (50 mg/M2) were given I.V. and orally, respectively, every 8 weeks. Remission of the neoplastic lesions within the liver was seen in 10 patients (4CR, 6PR). Five patients had stabilization of their lesion neoplasm for at least 4 months. The response rate in this study was 6/15 (40%) in patients with colon cancer metastatic to the liver. Toxicity was mainly hematologic and hepatic. Three patients experienced a platelet count below 25,000 and/or white blood count below 1000. Fifteen patients had hepatic toxicity showing elevation in SGOT and SGPT. The SGOT and SGPT returned to normal when the 5FUDR was discontinued. The combination of 5FUDR intraarterially, and Mito C and MeCCNU systemically, demonstrated activity in malignancies of the liver. This study proved that chemotherapy can be administered systemically and regionally with acceptable toxicity.

Administration, Oral↗
PubMed1989

Expression of mammalian O6-alkylguanine-DNA alkyltransferase in a cell line sensitive to alkylating agents.

Chinese hamster ovary cells (CHO) were co-transfected with pSV2neo and sheared DNA from either a human cell line (HT29) expressing high levels of O6-alkylguanine-DNA alkyltransferase (AGT) or from a cell line (BE) deficient in this activity. Cells expressing the selectable marker were obtained by exposure to G418 and colonies resistant to alkylation damage isolated by growth in the presence of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU). The number of colonies of cells expressing AGT activity arising after transfection with DNA from BE cells was similar to the number arising from cells exposed to HT29 DNA. Although the amount of AGT repair protein expressed in the transfectant colonies from this experiment was relatively low, these results indicate that repair of alkylation damage can be restored in AGT-deficient cells by transfection of human DNA from both repair-deficient and proficient cells. A separate transfection of CHOMG cells [a mutant of CHO cells resistant to the drug, methylglyoxal bis(guanylhydrazone) (MGBG)] with HT29 DNA and pSV2neo followed by selection of G418 and 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU) resulted in three colonies with high AGT levels. These transfectants had different growth rates and expressed levels of the AGT protein between 230 and 300 fmol/mg protein. The transfectants were as resistant to the cytotoxic effects of BCNU, Clomesone, methylnitrosourea (MNU) and 1-methyl-3-nitro-1-nitrosoguanidine (MNNG) as HT29 cells which were much more resistant than the parental CHOMG cells. Pretreatment of transfectant cells with 0.4 mM O6-methylguanine for 24 h reduced AGT activity to 14% basal levels, which upon removal of the base increased to approximately 74% basal level within 8 h. The sensitivity to the cytotoxic effects of both the chloroethylating and methylating agents was enhanced by treatment with O6-methylguanine. In the same manner, the number of BCNU-induced DNA interstrand cross-links increased in transfectant cells pretreated with O6-methylguanine. These results provide further evidence that the formation of methyl or chloroethyl adducts at the O6-position contribute significantly to cell lethality.

Alkylating Agents↗
PubMed1990

Formation of N2,3-ethanoguanine in DNA after in vitro treatment with the therapeutic agent, N-(2-chloroethyl)-N'-cyclohexyl-N-nitrosourea.

HPLC analyses of the bases released by acid from N-(2-chloroethyl)-N-nitrosourea-treated DNA and N-(2-chloroethyl)-N'-cyclohexyl-N-nitrosourea-treated DNA show the presence of a new guanine adduct, N2,3-ethanoguanine. This derivative can be synthesized at the monomer level by treating 2-hydroxyethylguanine with thionyl chloride. The product of this reaction, purified by HPLC, has been shown to have a mol. wt corresponding to ethanoguanine by mass spectrometry; NMR spectrometry also supports this structural assignment. The UV and fluorescence spectra are very similar to those of N2,3-ethenoguanine, providing evidence that the ethano bridge is attached between N2 and 3 positions. Proof that the derivative is N2,3-ethanoguanine comes from the fact that it can be converted to N2,3-ethenoguanine by dehydrogenation on a palladium catalyst. The discovery of this new derivative raises to four the number of tricylic derivatives that have been isolated from DNA treated with 2-haloethylnitrosoureas. The new adduct, N2,3-ethanoguanine, is closely related to an etheno adduct formed by chloroacetaldehyde, a metabolite of the human carcinogen vinyl chloride, and may have relevance to either the therapeutic or carcinogenic actions of the 2-haloethylnitrosoureas.

Chromatography, High Pressure Liquid↗