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 13,001 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Reports indicate that cancer of the prostate, soft tissue sarcomas, salivary gland tumors, and melanomas respond well to fast-neutron treatment. To better understand the action of fast neutrons on such tumor tissues, we have begun studies with the versatile Dunning rat prostate tumor system. In our initial studies with the R3327-AT1 subline we observed a relative biological effectiveness (RBE) of approximately 3 for single doses of 14-meV fast neutrons. As a continuation of those studies the present report discusses our findings following fractionated treatments with 10 equal fractions of 14-MeV fast neutrons or 60Co gamma rays at several dose levels per fraction. After either fractionated neutron or photon treatment the volume of the tumors continued to increase for 2 weeks and then reached a plateau, the level of which was dose dependent. Tumor growth resumed and no local control was observed. Analysis of the data using growth delay as biological end point yielded an RBE of approximately 4.2 +/- 1.3.
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PMID:Response of the rat Dunning R3327-AT1 prostate tumor to treatment with fractionated fast neutrons. 172 53

In order to study the mechanism of induction of mutations and chromosome aberrations by ionizing radiations, it is particularly useful to have available radiation-sensitive mutants. While several X-ray-sensitive rodent cell lines are available, they have been selected rather nonspecifically. It was determined that selection for resistance to the DNA replication/repair inhibitor, 1-beta-D-arabinofuranosylcytosine (ara-C), would permit production of a set of X-ray-sensitive mutant cell lines that would be defective in the resynthesis step of excision or recombination repair. Such mutant cells could also be used for the isolation and characterization of human DNA repair genes. In particular, it was predicted that the repair gene defective in individuals with ataxia telangiectasia (AT) might be amenable to study with ara-C-resistant (X-ray-sensitive) mutants, since additional studies, presented here, have shown that AT cells are resistant to ara-C. In the long term, it is hoped that determining the specific defect in AT might lead to an understanding of the possible role of defective repair in tumor induction and/or progression. The general approach used to isolate ara-C-resistant Chinese hamster ovary cell mutants was to treat cells with ethyl methanesulfonate and select in increasing concentrations of ara-C. Although several mutants were isolated, one in particular, Ara-CR213, has been studied most extensively. It was selected largely because it shows the greatest sensitivity to X-rays. Ara-CR213 cells were hypersensitive to the killing effect of X-rays with an LD10 of 2.5 Gy as compared to the wild-type cells that had an LD10 of 6 Gy. The mutant showed an increased frequency of X-ray-induced chromosomal aberrations in the G1 and G2 stages of the cell cycle compared to wild-type frequencies. There was no increase in sister chromatid exchange levels. All of these observations in Ara-CR213 are very similar to those made with AT cells in our and other laboratories. Even more important, complementation analysis of Ara-CR213 x AT hybrid cells indicated that the gene responsible for X-ray sensitivity of AT is also mutated in Ara-CR213 cells. Thus, Ara-CR213 appears to have a mutant phenotype and probably genotype that is very similar to, if not exactly the same as, those of AT. This makes it quite different from other X-ray-sensitive cells that have been isolated in other laboratories.
Cancer Res 1992 Jan 15
PMID:Isolation and characterization of a 1-beta-D-arabinofuranosylcytosine-resistant Chinese hamster ovary cell mutant that is also X-ray sensitive and is noncomplementary with ataxia telangiectasia cells. 172 6

Many grading systems for prostatic carcinoma exist; however, none allows pathologists to predict accurately the prognosis of individual patients. The Dunning R-3327 prostatic adenocarcinoma model consist of sublines of known metastatic potential which were indistinguishable until recently. A visual grading system of cancer cell motility distinguished the metastatic potentials of Dunning sublines maintained in vitro and was validated prospectively. We used this grading system to assess the metastatic potential of cells harvested directly from in vivo Dunning tumors. We graded the motility of cells from three Dunning sublines of low (less than 10%) (G, AT1, AT2) and three sublines of high (greater than 90%) AT3, (MAT-LyLu, PAT2) metastatic potential. Cells obtained from primary tumors were studied by time lapse videomicroscopy after passages 1, 3 and 5 in vivo and in vitro. Membrane ruffling, pseudopodal extension and cellular translation were graded 0-10. Serial analysis of mean and heterogeneity (coefficient of variation) of membrane ruffling, pseudopodal extension and cellular translation demonstrated that subline motility grades were assessed adequately by a sample of 10 cells. Motility did not depend upon whether cells were maintained in vitro or in vivo; however, motility increased with successive passages in four of six sublines. In 60 cells harvested directly from the fifth in vivo passage, three sublines of low metastatic potential were distinguished from three sublines of high metastatic potential (Student's t test, p less than 0.01). Individual cells from the sublines were identified correctly as high or low metastatic in 83, 78 and 70% of cases by membrane ruffling, pseudopodal extension and cellular translation respectively, and logistic regression analysis failed to improve classification accuracy. A visual grading system of cancer cell motility described the metastatic potential of in vivo neoplasms in the Dunning model and may warrant testing in human prostatic cancer.
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PMID:Prediction of metastatic potential by cancer cell motility in the Dunning R-3327 prostatic adenocarcinoma in vivo model. 173 34

Ataxia-telangiectasia (AT) is a heterogeneous autosomal recessive disorder marked by cerebellar ataxia, oculocutaneous telangiectases, hypersensitivity to ionizing radiation, immunodeficiency, and cancer susceptibility. AT is also a spontaneous chromosomal breakage syndrome, notable for tissue-specific cytogenetic changes and telomeric fusions. Molecular characterization of rearrangements specific to T-lymphocytes suggests that a DNA repair/processing defect is potentially responsible for the diverse array of chromosomal abnormalities observed in a variety of AT cell types.
Cancer Genet Cytogenet 1991 Oct 15
PMID:The cytogenetics of ataxia telangiectasia. 175 58

The clinical and immunological findings of 160 patients diagnosed over a period of twenty years as having ataxia-telangiectasia (AT) are presented. The study group composed of 68 females and 92 males were members of 117 families. The rate of parental consanguinity was 65 percent. The incidence of AT in 117 families was 36.6 percent. All patients had the characteristic facial and postural features of AT. The mean duration of follow-up of 160 patients was 6.35 years. Fifty patients had died during the follow-up (36 of pulmonary infections, 14 of malignancies). Somatic growth retardation was a prominent feature. Recurrent sinopulmonary infections were detected in 66 percent of patients. Two patients had hypothyroidism, one had diabetes mellitus, and one had both conditions. The incidence of malignancies was found to be 2.3 percent in the immediate relatives of the patients. The total lymphocyte count was low in 57 percent, and skin tests to PHA, candida, PPD and SK-SD were negative in 17.7%, 72.6%, 43.6%, and 78.2% of patients, respectively. In vitro blastogenic response to PHA was low in 61 percent of patients. The mean value of E-rosette formation was significantly lower than control values. Six patients had low serum IgG levels. The serum IgM level was high in 26.6 percent of patients and the IgA level was low or absent in 51.3 percent. There was no correlation between immune disturbance and duration of illness.
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PMID:Twenty-year follow-up of 160 patients with ataxia-telangiectasia. 181 37

The association between cancer and immunodeficiency is well established. In common variable immunodeficiency (CVI), a primary immunodeficiency disease characterized by low serum immunoglobulins and poor antibody production, we previously reported a total of 13 cancers in 11 individuals arising in continuously observed group of patients. Of the 13, 7 were NHL and 1 was a myeloma which progressed to lymphoma. We report here the histologic, immunologic, cytogenetic, and clinical features of these 8 NHL along with 3 new lymphomas which have appeared in this group (now 117 patients). From our studies, the lymphomas which have arisen in CVI share certain features with the lymphomas which appear in the childhood immunodeficient syndromes. Wiskott Aldrich Syndrome, Ataxia Telangiectasia, or severe combined immunodeficiency: they are similar in overall frequency (13%), are often B-cell in origin, and extranodal in location. However, unlike the lymphomas of the immunodeficient child, lymphomas in CVI may be more differentiated and secrete immunoglobulin. For CVI patients with stage I or II disease, as for non-Hodgkin lymphomas in general, the prognosis is good. In our group, NHL in CVI have appeared most often in females of the 5th to 7th decade and not in childhood. Cytogenetic studies in lymphomas show that cytogenic abnormalities, including chromosomal translocation, can be found in this group, but more studies will be needed to assess the frequency of these events.
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PMID:Non-Hodgkin lymphoma in common variable immunodeficiency. 182 73

We describe the application of a flow cytometric technique for assessing the radiation or drug sensitivity characteristics of human tumour cells. The technique makes use of the phenomenon that a red shift occurs in the fluorescence emission spectrum of a DNA-specific dye (Hoechst 33,342) as an increasing number of dye molecules bind to nuclear DNA. Intact, viable cells undergo a time-dependent spectral shift that can be distinguished from the rapid shift observed in cells with damaged membranes by the use of multiparametric flow cytometry. The responses of various human cell lines were compared, namely, those of normal and ataxia-telangiectasia (A-T) lymphoblastoid lines, a small-cell lung carcinoma line and its (in vitro) derived multidrug-resistant variants. A close correlation was found between dye toxicity and the degree of DNA binding of Hoechst 33,342 independent of cellular DNA content, with lymphoblastoid and multidrug-resistant small-cell lung cancer cells showing enhanced and restricted dye-binding rates, respectively. VP16- and radiation-induced cell kill was found to result in a quantifiable increase in the fraction of cells undergoing a rapid spectral shift and was capable of detecting the increased radiation sensitivity of A-T-derived cells. Spectral shift analysis provides a rapid method for assessing the responses of tumour cells to cytotoxic agents and for determining the general ability of cells to protect cellular DNA from a model DNA-binding agent (Hoechst 33,342) that participates in the multidrug resistance phenotype.
Cancer Chemother Pharmacol 1991
PMID:Detection of multidrug resistance and quantification of responses of human tumour cells to cytotoxic agents using flow cytometric spectral shift analysis of Hoechst 33,342-DNA fluorescence. 184 64

The cytogenetic characterization of CH cell line obtained by Epstein-Barr-virus transformation of the lymphocytes of a patient affected by ataxia telangiectasia is reported. Control CH cells and 2 subcultures treated with the mutagens R7000 or NQO were developed in parallel and studied. A common chromosome anomaly, a der(14) t(11;14) (q13.2;q32), was found in all the studied karyotypes, indicating that it occurred either in vivo or early in vitro. In non-treated cultures, additional anomalies were present in 6 derived subclones. All R-7000 treated cells had the same karyotype corresponding to one of the subclones observed without prior treatment. All NQO-treated cells acquired 2 common anomalies, and could be differentiated into 2 subclones because of the addition of a t(7;14) or a t(11;14). Chromosome 14 was involved in various rearrangements after breakage in band q11.2 or q12 in 6/8 subclones. This was not correlated with tumorigenicity, which was clearly increased in mutagen-treated cells as tested by in vitro growth in semi-solid medium and in vivo by grafts into nude mice or growth on the chorio-allantoic membrane of chick embryos. The CH cell line and its derivatives appear to be a promising in vitro system, showing various stages progressing towards malignancy, and reproducing a number of chromosome anomalies spontaneously occurring in AT patients.
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PMID:High recurrence of rearrangements involving chromosome 14 in an ataxia telangiectasia lymphoblastoid cell line and in its mutagen-treated derivatives. 184 69

Compared to normal controls from healthy subjects, cells cultured from patients with the autosomal recessive, cancer-prone disorder ataxia telangiectasia (AT) uniformly display impaired clonogenic survival, in concert with decreased inhibition of DNA synthesis, on exposure to ionizing radiation. In this study we have determined the effects of 4-nitroquinoline 1-oxide (4NQO), a partially radiomimetic chemical carcinogen, on colony-forming ability and rate of DNA synthesis in non-transformed skin fibroblasts strains derived from clinically normal volunteers and AT patients. Strain AT3BI, belonging to AT complementation group A, displayed substantial hypersensitivity to the lethal action of 4NQO, whereas the survival response of strain AT5BI (group D) did not differ significantly from that of the three normal controls. The 4NQO-hypersensitive AT3BI cells exhibited normal inhibition of DNA synthesis when treated with the chemical, as manifested by both dose-response and time-course measurements. However, 4NQO treatment decreased the rate of DNA synthesis to a much lesser degree in AT5BI than in normal strains. Hence, our data demonstrate unequivocally that, unlike that universally observed following exposure of AT cells to ionizing radiation, carcinogen-resistant DNA synthesis does not segregate with elevated cytotoxicity when cultured fibroblasts representing at least some genetic forms of AT (i.e. groups A and D) are damaged by 4NQO.
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PMID:Lack of correlation between hypersensitivity to cell killing and impaired inhibition of DNA synthesis in ataxia telangiectasia fibroblasts treated with 4-nitroquinoline 1-oxide. 189 54

Ataxia telangiectasia (AT) and T-prolymphocytic leukemia (T-PLL) have similar chromosome abnormalities. Cytogenetic findings reported in 5 patients with AT who developed T-cell leukemia revealed: inv(14)(q11q32) (1 case), tandem translocations of chromosome 14 with breakpoints at q11 and q32 (3 cases), and int. del(14)(q11q32) (1 case). Additional abnormalities were present in 4 patients of whom two had trisomy for 8q. Of 27 patients with T-PLL but without AT, investigated by us, 17 had inv(14)(q11q32) and 3 had tandem rearrangement of chromosome 14 with breaks at 14q11 and q32; 15 of them also had rearrangements resulting in trisomy 8q. Two of the leukemias supervening on AT had morphology and clinical course suggestive of T-PLL. Two other cases of AT studied by us developed typical T-PLL at a young age (18 and 39 years). T-cell clones carrying an inv(14), tandem t(14;14) and t(X;14) can be present in AT for long periods of time without evolving into leukemia. In T-PLL, inv(14) and t(14;14) always occurs with other chromosome abnormalities. We suggest that these additional chromosome abnormalities may be required for the leukemic transformation of AT. This is supported by one of the two AT cases studied by us in which a long-standing t(X;14) clone evolved with the formation of t(1;14)(p21;q11), t(8;22)(q24;q11) at the time of the development of T-PLL.
Cancer Genet Cytogenet 1991 Aug
PMID:Inversions and tandem translocations involving chromosome 14q11 and 14q32 in T-prolymphocytic leukemia and T-cell leukemias in patients with ataxia telangiectasia. 191 94


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