| 41. |
- Arbyn, M, et al.
(author)
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Virologic versus cytologic triage of women with equivocal pap smears: A meta-analysis of the accuracy to detect high-grade intraepithelial neoplasia
- 2004
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In: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 96:4, s. 280-293
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Journal article (peer-reviewed)abstract
- Background: The appropriate management of women with minor cytologic lesions in their cervix is unclear. We performed a meta-analysis to assess the accuracy of human papillomavirus (HPV) DNA testing as an alternative to repeat cytology in women who had equivocal results on a previous Pap smear. Methods: Data were extracted from articles published between 1992 and 2002 that contained results of virologic and cytologic testing followed by colposcopically directed biopsy in women with an index smear showing atypical cells of undetermined significance (ASCUS). Fifteen studies were identified in which HPV triage and the histologic outcome (presence or absence of a cervical intra-epithelial neoplasia of grade 11 or worse [CIN2+]) was documented. Nine, seven, and two studies also documented the accuracy of repeat cytology when the cutoff for abnormal cytology was set at a threshold of ASCUS or worse, low-grade squamous intraepithelial lesion (LSIL) or worse, or high-grade squamous intraepithelial lesion (HSIL) or worse, respectively. Random-effects models were used for pooling of accuracy parameters in case of interstudy heterogeneity. Differences in accuracy were assessed by pooling the ratio of the sensitivity (or specificity) of HPV testing to that of repeat cytology. Results: The sensitivity and specificity were 84.4% (95% confidence interval [CI] = 77.6% to 91.1%) and 72.9% (95% CI = 62.5% to 83.3%), respectively, for HPV testing overall and 94.8% (95% CI = 92.7% to 96.9%) and 67.3% (95% CI = 58.2% to 76.4%), respectively, for HPV testing in the eight studies that used the Hybrid Capture 11 assay. Sensitivity and specificity of repeat cytology at a threshold for abnormal cytology of ASCUS or worse was 81.8% (95% CI = 73.5% to 84.3%) and 57.6% (95% CI = 49.5% to 65.7%), respectively. Repeat cytology that used higher cytologic thresholds yielded substantially lower sensitivity but higher specificity than triage with the Hybrid Capture 11 assay. The ratio of the sensitivity of the Hybrid Capture 11 assay to that of repeat cytology at a threshold of ASCUS or worse pooled from the four studies that used both triage tests was 1.16 (95% CI = 1.04 to 1.29). The specificity ratio was not statistically different from unity. Conclusion: The published literature indicates that the Hybrid Capture 11 assay has improved accuracy (higher sensitivity, similar specificity) than the repeat Pap smear using the threshold of ASCUS for an outcome of CIN2+ among women with equivocal cytologic results. The sensitivity of triage at higher cytologic cutoffs is poor.
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| 42. |
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| 43. |
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| 44. |
- Bardi, G, et al.
(author)
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Tumor karyotype predicts clinical outcome in colorectal cancer patients
- 2004
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In: Journal of Clinical Oncology. - 1527-7755. ; 22:13, s. 2623-2634
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Journal article (peer-reviewed)abstract
- Purpose To investigate the prognostic value of the overall karyotypic features and specific chromosome aberrations in colorectal cancer (CRC). Patients and Methods Cytogenetic features of 150 primary CRCs investigated at the time of surgery were correlated with patient survival by univariate and multivariate analyses, using classical clinicopathologic parameters as covariates. Results In univariate analysis, in addition to tumor grade and clinical stage, structural aberrations as well as rearrangements of chromosomes 8 and 16 were significantly correlated with shorter overall survival. Karyotypic complexity, rearrangements of chromosomes 8 and 16, and loss of chromosome 4 were significantly correlated with shorter disease-free survival. In multivariate analysis, in addition to tumor grade, the type of chromosome aberrations (structural or numerical), ploidy, and loss of chromosome 18 came across as independent prognostic factors in the group of all patients. In the subset of patients with stage I and II carcinomas, none of the clinicopathologic variables could independently predict patient survival, whereas the presence of structural chromosomal aberrations was the only independent predictor of poor prognosis. In the subset of patients with stage III carcinomas, the presence of structural changes of chromosome 8 was a stronger independent predictor of prognosis than was tumor grade. Conclusion Cytogenetic tumor features are valuable predictors of prognosis in CRC patients. The tumor karyotype should therefore be taken into account in the clinical management of patients with this disease, especially for patients having cancers of the early or intermediate stages I, II, and III.
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| 45. |
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| 46. |
- Bengtsson, Therese
(author)
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Functional analysis of the alpha10beta1 integrin
- 2004
-
Doctoral thesis (other academic/artistic)abstract
- The aim of this thesis was to study the function of the integrin a10b1. Integrins mediate signals between cells and their environment and regulate several cellular processes such as cell migration, proliferation and differentiation. The a10b1 integrin is expressed mainly by chondrocytes, the only cell type present in cartilage, and facilitates binding of the chondrocytes to the extracellular matrix molecule collagen. However, the function of the a10b1 integrin in cartilage is not known. In this thesis we describe the structure of the mouse a10b1 integrin gene and report the finding of two alternatively spliced extracellular forms of the a10b1 integrin. We also demonstrate the chromosomal localization of the human and mouse a10 integrin genes. To analyze the role of this collagen-binding integrin during development and in adult mice we generated a mouse deficient in the a10b1 integrin, by gene targeting deletion. We found that a10b1–null mice suffered from a mild chondrodysplasia, and that they had shorter limbs than normal mice. The mutant mice showed structural defects in the growth plate and decreased chondrocyte proliferation. Further studies have revealed that the a10b1 integrin appears to be the only collagen-binding integrin expressed in the growth plate of 8-week old mice. Together, these data show that the a10b1 integrin plays an important role in the regulation of chondrocyte function and bone development.
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| 47. |
- Beral, Valerie, et al.
(author)
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Breast cancer and abortion: collaborative reanalysis of data from 53 epidemiological studies, including 83?000 women with breast cancer from 16 countries
- 2004
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In: The Lancet. - 1474-547X. ; 363:9414, s. 1007-1016
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Journal article (peer-reviewed)abstract
- BACKGROUND: The Collaborative Group on Hormonal Factors in Breast Cancer has brought together the worldwide epidemiological evidence on the possible relation between breast cancer and previous spontaneous and induced abortions. METHODS: Data on individual women from 53 studies undertaken in 16 countries with liberal abortion laws were checked and analysed centrally. Relative risks of breast cancer--comparing the effects of having had a pregnancy that ended as an abortion with those of never having had that pregnancy--were calculated, stratified by study, age at diagnosis, parity, and age at first birth. Because the extent of under-reporting of past induced abortions might be influenced by whether or not women had been diagnosed with breast cancer, results of the studies--including a total of 44000 women with breast cancer--that used prospective information on abortion (ie, information that had been recorded before the diagnosis of breast cancer) were considered separately from results of the studies--including 39000 women with the disease--that used retrospective information (recorded after the diagnosis of breast cancer). FINDINGS: The overall relative risk of breast cancer, comparing women with a prospective record of having had one or more pregnancies that ended as a spontaneous abortion versus women with no such record, was 0.98 (95% CI 0.92-1.04, p=0.5). The corresponding relative risk for induced abortion was 0.93 (0.89-0.96, p=0.0002). Among women with a prospective record of having had a spontaneous or an induced abortion, the risk of breast cancer did not differ significantly according to the number or timing of either type of abortion. Published results on induced abortion from the few studies with prospectively recorded information that were not available for inclusion here are consistent with these findings. Overall results for induced abortion differed substantially between studies with prospective and those with retrospective information on abortion (test for heterogeneity between relative risks: chi2(1) =33.1, p<0.0001). INTERPRETATION: Pregnancies that end as a spontaneous or induced abortion do not increase a woman's risk of developing breast cancer. Collectively, the studies of breast cancer with retrospective recording of induced abortion yielded misleading results, possibly because women who had developed breast cancer were, on average, more likely than other women to disclose previous induced abortions.
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| 48. |
- Berglund, Mattias, 1972-
(author)
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Molecular Characterization of Diffuse Large B-cell Lymphoma and Aspects of Transformation
- 2004
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Doctoral thesis (other academic/artistic)abstract
- Lymphomas are a heterogeneous group of neoplasias originating from B- or T-lymphocytes. In this thesis, we determined the genetic and immunophenotypic characterization of DLBCL and their prognostic impact. Moreover, genomic alterations associated with the transformation to DLBCL from Hodgkin lymphoma (HL) and follicular lymphoma (FL) were elucidated. In order to outline the impact of cytogenetic as well as immunophenotypic prognostic markers in DLBCL, we firstly studied a series of 54 DLBCL tumors using comparative genomic hybridization (CGH) and we identified several frequently occurring chromosomal imbalances. Loss of 22q was more often found in the diagnostic tumors with a more advanced clinical stage, while gain of 18q21 was more commonly identified in relapses. Secondly, we correlated the expression patterns of CD10, bcl-6, IRF-4 and bcl-2 with clinical parameters in a series of 173 de novo DLBCL patients. Patients with a germinal center (GC) phenotype displayed a better survival than the non-GC group. Expression of bcl-6 and CD10 was correlated with a better survival while bcl-2 expression was associated with a poor prognosis.In approaching the HL transformation, two novel B-cell lines (U-2932 and U-2940), derived from patients with DLBCL following HL, were characterized. Interestingly, a translocation with materials from 2q and 7q as well as loss of material on 6q was found in both cell lines. For FL transformation, we assessed chromosomal alterations in a panel of 28 DLBCL patients with a previous history of FL. The DLBCL tumors displayed more chromosomal imbalances compared to FL tumors. Loss of 6q16-21 and gain of 7pter-q22 were more commonly found in the DLBCL counterparts, suggesting the chromosomal location of putative genes that may be involved in the transformation process.
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| 49. |
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| 50. |
- Boman, Krister K, et al.
(author)
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Life after cancer in childhood : social adjustment and educational and vocational status of young-adult survivors
- 2004
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In: Journal of pediatric hematology/oncology (Print). - : Ovid Technologies (Wolters Kluwer Health). - 1077-4114 .- 1536-3678. ; 26:6, s. 354-62
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Journal article (peer-reviewed)abstract
- PURPOSE: To evaluate the long-term social effect of illness and its treatment on young-adult survivors of pediatric cancer by addressing a selection of general social adjustment criteria.METHODS: In a cross-sectional case-control study, 30 young-adult survivors of childhood cancer were compared with (1). controls with no history of serious illness, matched by sex, age, and geographic area of residence, and (2). general population norms on the subject of educational and vocational factors, habitation, family/partner relationships, parenthood, and leisure activities.RESULTS: The educational status of survivors was similar to that of controls, although a smaller proportion of the patients expressed concrete plans for future vocational or educational advancement. Survivors had less frequently entered higher education compared with general population norms. A longer duration of treatment was related to a lower estimated socioeconomic level, and poor psychological coping with the illness experience was associated with the fact that they were still living with their parents, a shorter education, and a lower socioeconomic level.CONCLUSIONS: The social, vocational, and educational adjustment of relapse-free survivors from childhood cancer appears as only moderately, if at all, negatively affected by the illness and treatment history. However, the treatment intensity and particularly the survivors' coping with their illness experience may influence their ability to achieve long-term social goals. These findings suggest that special attention should be given to matters concerning education and partner relationships at long-term follow-up of pediatric cancer patients.
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