| 41. |
- Tobin, Gerard, et al.
(författare)
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Subsets with restricted immunoglobulin gene rearrangement features indicate a role for antigen selection in the development of chronic lymphocytic leukemia.
- 2004
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 104:9, s. 2879-85
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Tidskriftsartikel (refereegranskat)abstract
- Pseudohypoaldosteronism type I (PHA1) is a condition associated with salt wasting leading to dehydration, hypotension, hyperkalemia, and metabolic acidosis. Sporadic cases and two familial forms, one autosomal dominant and one autosomal recessive form, have been described. The autosomal dominant or sporadic form manifests milder salt wasting that remits with age. Mutations in the gene encoding the mineralocorticoid receptor (MR) have been identified in patients with the autosomal dominant inheritance. However, recent studies suggest that the autosomal dominant and sporadic forms are genetically heterogeneous and that additional genes might be involved. We report on the study of 15 members of a Swedish five-generation family with the autosomal dominant form of PHA1. Interestingly, neuropathy was found in two of five affected individuals. A novel heterozygous nonsense mutation C436X in exon 2 was identified in the index patient by linkage analysis, PCR, and direct sequencing of the MR gene. Analysis of the family demonstrated that the mutation segregated with PHA1 in the family. It is unclear whether the neuropathy is associated with the mutation found. Our results together with previously published data suggest that loss-of-function mutations of the MR gene located at 4q31.1, commonly are associated with the autosomal dominant form of PHA1.
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| 42. |
- Jerkeman, Mats
(författare)
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Aggressive lymphoma
- 2000
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Aggressive lymphoma is a rapidly growing tumour of lymphocyte origin, potentially curable with chemotherapy. In a trial by the Nordic Lymphoma Group, 405 patients with aggressive lymphoma were included, and randomised to receive either the standard chemotherapy regimen, CHOP, or a weekly multidrug regimen, MACOP-B. In this trial, MACOP-B was not superior in terms of response, failure-free or overall survival, but was associated with more non-haematological toxicity and with more pronounced negative effects on health-related quality of life (HRQOL). In this study, we were able to validate the prognostic impact of the International Prognostic Index (IPI). In 92 patients, assessment of HRQOL was performed before, during, and after chemotherapy. In this population, chemotherapy was associated with relatively little negative impact on HRQOL, compared to a reference population. In a multivariate analysis of prognostic factors, pre-treatment global quality was identified as an independent prognostic factor. In 259 patients, immunohistochemical analysis of Ki-67, BCL2, p53 and P-glycoprotein was performed. In a multivariate model, high BCL2 expression, high p53 expression and both very high and low Ki-67 expression were associated with poor prognosis, and were shown to provide additional prognostic information to the IPI. Assessment of BCL2 is proposed to be included as a routine procedure in patients with aggressive lymphoma. In 32 patients with diffuse large B-cell lymphoma (DLBL), frozen lymphoma tissue was available, enabling assessment of BCL6 rearrangement with Southern blot. BCL6 rearrangement was detected in six of 50 patients (12%) and among these, a trend towards superior overall and failure-free survival was noted. In a consecutive series of 81 patients with cytogenetically analysed DLBL, the prognostic impact of cytogenetic aberrations of previously proposed prognostic importance, was analysed. In univariate analysis, der(1q)(21-23), was associated with inferior overall survival. Among patients receiving anthracyclin-based chemotherapy, der(1q)(21-23) remained an adverse prognostic factor in a multivariate analysis, stratified for IPI. The implications of these results in relation to current findings in prognostication and treatment of patients with aggressive lymphoma is discussed.
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| 43. |
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| 44. |
- Graflund, Marianne, et al.
(författare)
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Immunohistochemical expression of p53, bcl-2, and p21WAF1/CIP1 in early cervical carcinoma : Correlation with clinical outcome
- 2002
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Ingår i: International Journal of Gynecological Cancer. - Malden, USA : BMJ. - 1048-891X .- 1525-1438. ; 12:3, s. 290-298
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Tidskriftsartikel (refereegranskat)abstract
- The objective of this study was to assess the value of p53, bcl-2, and p21WAF1/CIP1 immunoreactivity as predictors of pelvic lymph node metastases (LNM), recurrences, and death due to the disease in early stage (FIGO I-II) cervical carcinomas. FIGO stage, type of histopathology, and tumor grade were also evaluated in this series of patients treated by radical hysterectomy (Wertheim-Meigs) between 1965 and 1990. A total of 172 patients were included. A tumor was regarded as positive when more than 30% of the neoplastic cells exhibited immunoreactivity. Positive immunostaining was found in 8.9% for p53, in 43.5% for bcl-2, and in 25.0% for p21WAF1/CIP1. None of them was able to predict LNM or clinical outcome. Presence of LNM, tumor recurrence, and death from disease were significantly associated with the FIGO stage (P = 0.014, P = 0.009, and P = 0.001, respectively). The 5-year cancer-specific survival rate was 91.6% and the overall survival rate was 90.5%. It was concluded that immunohistochemically detected p53, bcl-2, and p21WAF1/CIP1 appeared to be of no predictive value with regard to LNM, tumor recurrences, or long-term survival in early cervical carcinomas.
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| 45. |
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| 46. |
- Aus, Gunnar, et al.
(författare)
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Prognostic Factors and Survival in Node-Positive (N1) Prostate Cancer : A Prospective Study Based on Data from a Swedish Population-Based Cohort
- 2003
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Ingår i: European Urology. - 0302-2838 .- 1873-7560. ; 43:6, s. 627-631
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Tidskriftsartikel (refereegranskat)abstract
- Objective: At presentation of prostate cancer, patients with proven lymph node metastasis (N1) are comparatively rare. It is difficult to give prognostic information based on the present literature. The aim of this study was to evaluate the impact of known risk factors in patients with pelvic node involvement and without distant metastasis. Methods: From the population-based, prospective prostate cancer tumour registry of the South–East Region in Sweden, we collected data on all 181 patients with N1, M0 prostate cancer diagnosed from January 1987 to October 2000 with a follow-up to December 2001. Mean follow-up was 62 months. Pre-operative risk factors as age, T-category, serum PSA, tumour grade and also primary treatment given was correlated to the outcome. Results: Median age at diagnosis was 65 years. Cancer-specific survival was highly variable with 5-year survival of 72%, a median of 8 years and the projected 13-year figure was 31%. T-category, age, PSA or treatment did not affect the outcome while poorly differentiated tumours had a tendency towards lower cancer-specific survival (p=0.0523) when compared to well and moderately differentiated tumours. Conclusions: This population-based cohort of prostate cancer patients with pelvic node involvement treated principally with non-curative intent had a median cancer-specific survival of 8 years. Preoperatively known risk factors seem to have but a modest impact on the prognosis for patients in this stage of the disease.
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| 47. |
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| 48. |
- Engellau, Jacob
(författare)
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Prognostic factors in soft tissue sarcoma. Tissue microarray for immunostaining, the importance of whole-tumor sections and time-dependence.
- 2004
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Ingår i: Acta Orthopaedica Scandinavica. - : Medical Journals Sweden AB. - 0001-6470. ; 75:Suppl. 314, s. 5-5
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In adult soft tissue sarcoma (STS) of the extremities and trunk wall, improved prognostic factors are needed to identify patients at high-risk for metastasis. Various factors are included in the many prognostic systems currently in use and the prognostic value of immunohistochemical (IHC) expression of biological markers is unclear. The tissue-preserving, high throughput tissue microarray (TMA) technique for analysis of immunohistochemical expression of biological markers was validated for Ki-67, and was found to yield results comparable to conventional staining methods. TMA was used to study the IHC expression of multiple markers (Ki-67, p53, cyclin A, bcl-2, ß-catenin, CD44, and Pgp) in 218 malignant fi brous histiocytomas (MFH) and in 140 mixed STS. In the MFH series, tumor size and Ki-67, as the only IHC marker, provided independent prognostic information. In the mixed STS series whole-tumor sections were used and TMA was performed in the peripheral tumor growth zone. Whole-tumor sections facilitated assessment of the strong independent prognostic factors for metastasis vascular invasion, hazard ratio (HR) 3.5, tumor necrosis (HR 2.8), and tumor growth pattern (HR 3.2), and the latter also correlated with local recurrence (LR). In comparison, histological malignancy grade, tumor size, and depth were not of independent prognostic value. When TMA was performed from the peripheral tumor growth zone, the IHC expression of Ki-67 (HR 1.9), ß-catenin (HR 2.7), CD44 (HR 2.1) and Pgp (HR 2.4) were independent prognostic factors. Finally, prognostic factors were found to be time-dependent, and most factors lost their prognostic value after 2 years, whereas LR was a strong prognostic factor for metastasis whenever it occurred.
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| 49. |
- Hautaniemi, S, et al.
(författare)
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A strategy for identifying putative causes of gene expression variation in human cancers
- 2004
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Ingår i: Journal of the Franklin Institute. - : Elsevier BV. - 0016-0032. ; 341:1-2, s. 77-88
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Tidskriftsartikel (refereegranskat)abstract
- The majority of microarray studies focus on analysis of gene expression differences between various specimens or conditions. However, the causes of this variability from one cancer to another, from one sample to another and from one gene to another often remain unknown. In this study, we present a systematic procedure for finding genes whose expression levels are altered due to an intrinsic or extrinsic explanatory phenomenon. The procedure consists of three stages: preprocessing, data integration and statistical analysis. We tested and verified the utility of this approach in a case study, where expression and copy number levels of 13,824 genes were determined in 14 breast cancer cell lines. The procedure resulted in identification of 92 genes whose expression levels could be explained by the variability of gene copy number. This set includes several genes that are known to be both overexpressed and amplified in breast cancer. Thus, these genes may represent an important set of primary, genetically altered genes that drive cancer progression. (C) 2003 The Franklin Institute.
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| 50. |
- Jahnson, Staffan, et al.
(författare)
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Tumor mapping of regional immunostaining for p21, p53, and mdm2 in locally advanced bladder carcinoma
- 2000
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Ingår i: Cancer. - New York, USA : John Wiley & Sons. - 0008-543X .- 1097-0142. ; 89:3, s. 619-629
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Tidskriftsartikel (refereegranskat)abstract
- Background: The aim of this study was to elucidate the associations among immunostaining for p53, p21, and mdm2; their respective expression within each tumor; and the value of these variables for predicting treatment outcome after cystectomy for patients with locally advanced bladder carcinoma.Methods: The hospital records from all 173 patients treated with cystectomy for locally advanced urothelial bladder carcinoma between 1967 and 1992 were retrospectively reviewed. Three consecutive sections from biopsies taken before any treatment were stained using the standard immunohistochemical technique for p53, p21, and mdm2, respectively. The cutoff limit was 20% or more for positive p53 expression and 10% or more for positive p21 and mdm2 expression.Results: Positive immunostaining was observed for p53 in 98 tumors (57%), for p21 in 89 tumors (51%), and for mdm2 in only 16 tumors (9%). The only association found between immunostaining for the three antibodies was that most mdm2-positive tumors had positive p21 expression. Tumor mapping of regional immunostaining showed no association between immunostaining for p53 and p21. In a proportional hazards analysis, no association was found between the results of immunostaining for the three antibodies and treatment outcome.Conclusions: Positive or negative expression of p53, p21, or mdm2, or combinations of these, was not associated with cancer specific mortality after cystectomy for bladder carcinoma. There was no association between immunostaining for p21 and p53, whereas positive immunostaining for mdm2 was observed in a minority of the tumors. These results indicate that, in addition to p21, p53, and mdm2, there are other oncoproteins and tumor suppressor proteins along the p53 pathway that are involved in tumor development and progression.
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