| 21. |
- Axmon, Anna, et al.
(författare)
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CYP1A1 and GSTM1 polymorphisms affect urinary 1-hydroxypyrene levels after PAH exposure
- 2000
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Ingår i: Carcinogenesis. - : Oxford University Press. - 0143-3334 .- 1460-2180. ; 21:4, s. 669-676
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Tidskriftsartikel (refereegranskat)abstract
- Certain human biotransformation enzymes have been implicated in the formation and scavenging of the ultimate reactive metabolites, the diolepoxides, from polycyclic aromatic hydrocarbons (PAHs). In the present study, performed on aluminum smelter workers, we have analyzed airborne PAH, the pyrene metabolite 1-hydroxypyrene (1-OHP) in urine, and genotypes for biotransformation enzymes involved in PAH metabolism. The aim was to evaluate the correlation between external exposure and biomarkers of exposure and to investigate to what extent genetic polymorphism in metabolic enzymes can explain interindividual variation in urinary 1-OHP levels. DNA was prepared from blood samples from 98 potroom workers and 55 controls and altogether eight polymorphisms in the CYP1A1, mEH, GSTM1, GSTP1 and GSTT1 genes were analyzed. The 1-OHP excretion was found to correlate significantly (P 100-fold) and univariate and multivariate regression analyses were used to find the variables that could determine differences in excretion. The variation could, to some degree, be explained by differences in exposure to airborne particulate-associated PAHs, the use of personal respiratory protection devices, smoking habits and genetic polymorphisms in the cytochrome P450 1A1, GSTM1 and GSTT1 enzymes. The part of the variance that could be explained by differences in biotransformation genotypes seemed to be of the same order of magnitude as the variance explained by differences in exposure. In the control group as well as in the occupationally exposed group, the highest 1-OHP levels were observed in individuals carrying the CYP1A1 Ile/Val genotype who were also of the GSTM1 null genotype. The results show that urinary 1-OHP is a sensitive indicator of recent human exposure to PAHs and that it may also to some extent reflect the interindividual variation in susceptibility to PAHs.
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| 22. |
- Björk-Eriksson, Thomas, 1960, et al.
(författare)
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Fewer problems with dry nasal mucous membranes following local use of sesame oil
- 2000
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Ingår i: Rhinology. - 0300-0729. ; 38:4, s. 200-3
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Tidskriftsartikel (refereegranskat)abstract
- Many people experience problems with a dry nasal mucous membrane, often without wondering why. Their noses itch and burn and dried mucus collects there. These problems are exacerbated during the winter, in air-conditioned environments and after nasal irradiation. Twenty patients experiencing problems with dryness of the nose were selected from outpatient clinics, together with twenty patients who had previously undergone nasal irradiation. During the first five days no treatment was administered. For the following twenty days the patients sprayed sesame oil into each nostril three times a day. For the last five days no treatment was given. When both groups received treatment and sprayed sesame oil (Nozoil) in their noses, the nasal problems decreased significantly. The greatest effect is exerted on dryness. The side effects from using this oil are few in number and mild.
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| 23. |
- Björk-Eriksson, Thomas, 1960, et al.
(författare)
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Tumor radiosensitivity (SF2) is a prognostic factor for local control in head and neck cancers
- 2000
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Ingår i: Int J Radiat Oncol Biol Phys. - 0360-3016. ; 46:1, s. 13-9
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To evaluate prospectively the prognostic value of SF2 for local control and survival in patients undergoing radiation therapy for head and neck cancers. METHODS AND MATERIALS: Following informed consent tumor specimens were obtained from 156 patients with primary carcinomas of the head and neck region. The specimens were assessed for the ability to grow in vitro (colony forming efficiency, CFE) and inherent radiosensitivity measured as the surviving fraction at 2 Gy (SF2) using a soft-agar clonogenic assay. Patients were treated mainly with neoadjuvant chemotherapy plus radiation therapy usually as a combination of accelerated external beam and interstitial radiotherapy. The probabilities of local control and survival were analyzed by univariate, bivariate and Cox multivariate analyses. RESULTS: Successful growth was achieved in 110/156 specimens and SF2 values were obtained from 99/156. Eighty four out of these patients underwent radical treatment. The median SF2 value for the 84 tumors was 0.40. At a mean follow-up time of 25 months (range 7-65) the median SF2 value of tumors from 14 patients who developed local recurrence was 0.53, which was significantly higher than the median of 0.38 for tumors from 70 patients without local recurrence (p = 0.015). Tumor SF2 was a significant prognostic factor for local control (p = 0.036), but not for overall survival (p = 0.20). Tumor SF2 was an independent prognostic factor for local control within bivariate and Cox multivariate analyses. CONCLUSIONS: This study has shown that tumor radiosensitivity measured as SF2 is a significant prognostic factor for local control in head and neck cancers.
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| 24. |
- Boiesen, P, et al.
(författare)
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Histologic grading in breast cancer--reproducibility between seven pathologic departments. South Sweden Breast Cancer Group
- 2000
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 39:1, s. 41-45
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Tidskriftsartikel (refereegranskat)abstract
- Histologic grade, including tubular formations, nuclear grade, and mitotic activity, is a well-documented prognostic factor in breast cancer. In comparison with other prognostic parameters, the evaluation of histologic grade is cheap and can be performed, in principle, in all cases of breast cancer. One possible disadvantage is that the evaluation may vary between different pathological departments. The aim of the present work was therefore to study the reproducibility of the histologic grading system by distributing haematoxylin-erythrosin-stained slides from 93 invasive breast cancers to the seven pathology departments within the southern healthcare region of Sweden. The evaluation was performed blindly and without any knowledge of other clinical parameters. In 31% of the cases the same histologic grade was obtained for all departments. The overall mean kappa was 0.54, indicating a moderate reproducibility. Of the three factors included in histologic grade, the agreement was best for tubular formations and poorest for nuclear grade and mitotic activity. The overall moderate reproducibility should be considered when the clinical usefulness of histologic grading is compared with other prognostic instruments.
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| 25. |
- Boman, K, et al.
(författare)
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Long-term coping in childhood cancer survivors : influence of illness, treatment and demographic background factors
- 2000
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Ingår i: Acta Paediatrica. - 0803-5253 .- 1651-2227. ; 89:1, s. 105-11
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Tidskriftsartikel (refereegranskat)abstract
- In 30 survivors of childhood cancer, long-term psychological coping with experience of disease and treatment was studied in relation to factors associated with illness, treatment and demographic background. Coping was assessed in a prior study, in which three groups of varying levels of coping where delineated (good, 40%; intermediate, 33%; poor, 27%, coping). The present study showed that poor individual coping was related to diagnosis, a shorter time of continuous complete remission, more severe illness and treatment impairments, and lower scores on a test of intellectual abilities. In addition, a longer time of treatment tended to be followed by poorer coping. However, no association was found for gender, parents' occupational level, age at illness onset, neuro-cranial irradiation, irradiation dose (total) or age at investigation. A tentative path-analysis was executed, displaying a model for the relationships between medical and demographic background variables, and for their influence on coping. It was concluded that a complex of factors--associated particularly with severity of disease and treatment--appears to be related to, and affects, coping with the illness experience. Patients' long-term coping with their illness trauma is most likely determined by multiple factors. Intellectual capabilities are related to coping.
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| 26. |
- Borg, Åke, et al.
(författare)
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High frequency of multiple melanomas and breast and pancreas carcinomas in CDKN2A mutation-positive melanoma families
- 2000
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Ingår i: Journal of the National Cancer Institute. - 0027-8874. ; 92:15, s. 6-1260
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: : Inherited mutations in the CDKN2A tumor suppressor gene, which encodes the p16(INK4a) protein, and in the cyclin-dependent kinase 4 (CDK4) gene confer susceptibility to cutaneous malignant melanoma. We analyzed families with two or more cases of melanoma for germline mutations in CDKN2A and CDK4 to elucidate the contribution of these gene defects to familial malignant melanoma and to the occurrence of other cancer types.METHODS: : The entire CDKN2A coding region and exon 2 of the CDK4 gene of an affected member of each of 52 families from southern Sweden with at least two cases of melanoma in first- or second-degree relatives were screened for mutations by use of polymerase chain reaction-single-strand conformation polymorphism analysis. Statistical tests were two-sided.RESULTS: : CDKN2A mutations were found in 10 (19%) of the 52 families. Nine families carried an identical alteration consisting of the insertion of arginine at position 113 of p16(INK4a), and one carried a missense mutation, in which the valine at position 115 was replaced with a glycine. The 113insArg mutant p16(INK4a) was unable to bind cdk4 and cdk6 in an in vitro binding assay. Six of the 113insArg families had at least one member with multiple primary melanomas; the 113insArg families also had a high frequency of other malignancies-in particular, breast cancer (a total of eight cases compared with the expected 2.1; P =.0014) and pancreatic cancer (a total of six cases compared with the expected 0.16; P<.0001). Families with breast cancer also had a propensity for multiple melanomas in females, suggesting that a sex-dependent factor may modify the phenotypic expression of CDKN2A alterations.CONCLUSIONS: : Our findings confirm that the majority of CDKN2A-associated melanoma families in Sweden are due to a single founder mutation. They also show that families with the CDKN2A 113insArg mutation have an increased risk not only of multiple melanomas and pancreatic carcinoma but also of breast cancer.
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| 27. |
- Bratt, O, et al.
(författare)
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Risk perception, screening practice and interest in genetic testing among unaffected men in families with hereditary prostate cancer
- 2000
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Ingår i: European Journal of Cancer. - 0959-8049. ; 36:2, s. 235-241
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Tidskriftsartikel (refereegranskat)abstract
- Approximately 5-10% of prostate cancer cases are caused by dominantly inherited susceptibility to the disease. Although advances have been made in research concerning the genetic mechanisms of hereditary prostate cancer, little is known about the psychological consequences for men at high risk of developing the disease. The aims of the present study were to examine risk perception, interest in genetic investigations, cancer-specific worry, and screening practice among unaffected men, aged 40-72 years old, with a pedigree consistent with hereditary prostate cancer and an estimated lifetime risk of prostate cancer of 35-45%. A questionnaire was sent by mail to 120 subjects, of whom 110 responded. Most of the men (n = 90, 82%) worried about having an inherited susceptibility to prostate cancer, and 34 (31%) claimed that worry about prostate cancer affected their daily life (3 (3%) fairly much, 31 (28%) slightly). As many as 40% of the study subjects perceived their lifetime risk of prostate cancer as 67% or more. Perceived high risk was associated with symptoms of depression and with cancer worry affecting daily living. Two-thirds of the men aged 50 years old or more were regularly screened for prostate cancer. Subjects with high levels of cancer-specific stress, as measured by the avoidance subscale of the Impact of Event Scale, were less likely to opt for screening. Almost all of the men (94%) were interested in presymptomatic genetic testing (84 (76%) "definitely yes" and 20 (18%) "probably yes"). We conclude that hereditary susceptibility to prostate cancer has significant psychological consequences although it rarely causes psychiatric morbidity. The present study underlines the importance of giving thorough, repeated information to men at high risk of prostate cancer.
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| 28. |
- Carlomagno, F, et al.
(författare)
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Comparison of DNA repair protein expression and activities between human fibroblast cell lines with different radiosensitivities.
- 2000
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Ingår i: International journal of cancer. Journal international du cancer. - 0020-7136. ; 85:6, s. 845-9
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Tidskriftsartikel (refereegranskat)abstract
- In order to investigate the molecular basis of variation in response to ionising radiation (IR) in radiotherapy patients, we have studied the expression of several genes involved in DNA double-strand break repair pathways in fibroblast cell lines. Ten lines were established from skin biopsies of cancer patients with different normal-tissue reactions to IR, and 3 from a control individual. For all 10 test cell lines, the cellular radiosensitivity was also known. Using Western blots we measured, in non-irradiated cells, the basal expression levels of ATM, Rad1 and Hus1, involved in the control of cellular DNA damage checkpoints, together with DNA-PKcs, Ku70, Ku80; XRCC4, ligaseIV and Rad51, involved in radiation- induced DSB repair. We also analysed the in vitro enzymatic activities, under non-irradiated conditions, of the DNA-PK and XRCC4/ligaseIV complexes. The levels of expression of the different proteins were similar in all the cell lines, but the activities of the DNA-PK and XRCC4/ligaseIV complexes showed some differences. These differences did not correlate with either the normal tissue response of the patient in vivo or with cellular radiation sensitivity in vitro. The activity differences of these enzyme complexes, therefore, do not account for the variation of responses seen between patients.
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| 29. |
- Ceballos, Eva, et al.
(författare)
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c-Myc antagonizes the effect of p53 on apoptosis and p21WAF1 transactivation in K562 leukemia cells
- 2000
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Ingår i: Oncogene. - : Springer Science and Business Media LLC. - 0950-9232 .- 1476-5594. ; 19, s. 2194-2204
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Tidskriftsartikel (refereegranskat)abstract
- c-myc protooncogene positively regulates cell proliferation and overexpression of c-myc is found in many solid tumors and leukemias. In the present study we used the K562 human myeloid leukemia cell line as a model to study the functional interaction between c-Myc and p53. Using two different methods, we generated K562 transfectant cell lines with conditional expression of either c-Myc or p53. The cells expressed the p53Vall35 mutant, which adopts a wild-type conformation at 32 degrees C, while c-Myc induction was achieved with a zinc-inducible expression vector. We found that p53 in wild-type conformation induces growth arrest and apoptosis of K562. Expression of c-Myc significantly attenuated apoptosis and impaired the transcriptional activity of p53 on p21WAF1, Bax and cytomegalovirus promoters. The impairment of p21WAF1 transactivation by c-Myc was confirmed by transfection of a c-Myc-estrogen receptor fusion protein and by induction of c-myc by zinc in transfected cells. Also, p53-mediated up-regulation of p21WAF1 mRNA protein were significantly reduced by c-Myc, while Bax levels were unaffected. Consistently, c-Myc increased cyclin-dependent kinase 2 activity in K562 cells expressing p53 in wild-type conformation. These results suggest that c-Myc overexpression may antagonize the pro-apoptotic function of p53, thus providing a molecular mechanism for the frequently observed deregulation of c-myc in human cancer.
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| 30. |
- Cervenak, L, et al.
(författare)
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Abolished angiogenicity and tumorigenicity of Burkitt lymphoma by interleukin-10
- 2000
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Ingår i: Blood. - 0006-4971. ; 96:7, s. 73-2568
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Tidskriftsartikel (refereegranskat)abstract
- Because of its immunosuppressive properties, interleukin-10 (IL-10) is thought to play an important role in a number of human disease states, including inflammation, autoimmunity, and transplant rejection. In this study, we demonstrate that introduction of human or viral IL-10 genes into Burkitt's lymphoma cells markedly reduced their ability to grow as subcutaneous (sc) tumors in SCID mice. In vivo assays for angiogenesis revealed an inhibition of the angiogenic capacity of the IL-10-transfected lines. Recombinant human IL-10 abolished and viral IL-10 reduced vascular endothelial growth factor (VEGF)-165-induced neovascularization. Furthermore, IL-10 blocked the VEGF- and fibroblast growth factor (FGF)-2-induced proliferation of microvascular endothelial cells in vitro. The current observations suggest a direct role for IL-10 in the prevention of angiogenesis in human lymphoid malignancies.
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