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Träfflista för sökning "hsv:(MEDICIN OCH HÄLSOVETENSKAP) hsv:(Klinisk medicin) hsv:(Cancer och onkologi) srt2:(2000-2004)"

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  • Zhou, ZY, et al. (författare)
  • A retrospective analysis of health care costs for bone fractures in women with early-stage breast carcinoma
  • 2004
  • Ingår i: Cancer. - John Wiley & Sons. - 1097-0142. ; 100:3, s. 507-517
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND. in this retrospective data base study, the authors sought to estimate direct costs for bone fractures in women age 65 years with early-stage breast carcinoma and to compare those costs with treatment costs for bone fractures in older women without early-stage breast carcinoma. METHODS. Direct costs for bone fractures in patients with early-stage breast carcinoma, which consist of excess treatment costs for bone fracture and excess costs of long-term care for bone fracture, were evaluated by using the 1997-1998 Standard Analytical File. The statistical significance of the difference in inpatient costs, medical treatment costs, and long-term care admission rates were determined with the t test and the Fisher chi-square test, respectively. RESULTS. For older women with early-stage breast carcinoma, the direct costs for bone fracture were estimated at $45,579, and 57% of those costs came from treating the bone fracture (32% came from inpatient hospital costs, and 25% came from noninpatient hospital costs), 25% came from other excess treatment costs, and 18% came from excess long-term care costs. The women who had early-stage breast carcinoma and sustained bone fracture did not differ significantly from the women without early-stage breast carcinoma who sustained a bone fracture. CONCLUSIONS. Bone fracture was associated with high direct costs in older women with early-stage breast carcinoma. Additional research should include appropriate, incidence-based studies to investigate the potential benefit of an intervention for preventing bone fracture in this increasingly large patient population.
  • Zhou, ZJ, et al. (författare)
  • Deletion of laminin-8 results in increased tumor neovascularization and metastasis in mice
  • 2004
  • Ingår i: Cancer Research. - American Association for Cancer Research Inc.. - 1538-7445. ; 64:12, s. 4059-4063
  • Tidskriftsartikel (refereegranskat)abstract
    • Laminin-8 (alpha4beta1gamma1) is one of the major laminin isoforms expressed in vascular endothelial basement membranes. Here we show that deletion of laminin-8 in mice affects angiogenesis under pathological conditions. Murine tumor models used in laminin alpha4-deficient mice results in hyperneovascularization and significant promotion of tumor growth and metastasis. The higher tumor growth rates in mutant mice correlate with decreased tumor cell apoptosis. Depletion of laminin alpha4 chain may alter the structure of vascular basement membranes, leading to increased angiogenesis. Our data suggest that the laminin-8 plays a critical role in the regulation of pathological angiogenesis.
  • Åkervall, Jan, et al. (författare)
  • Chromosomal translocations involving 11q13 contribute to cyclin D1 overexpression in squamous cell carcinoma of the head and neck
  • 2002
  • Ingår i: International Journal of Oncology. - D.A. Spandidos. - 1019-6439. ; 20:1, s. 45-52
  • Tidskriftsartikel (refereegranskat)abstract
    • CCND1 amplification results in cyclin D1 overexpression. However, other unidentified genetic mechanisms contribute to enhanced gene expression. In the present study, 32 squamous cell carcinoma of the head and neck (SCCHN) were investigated regarding chromosomal abnormalities involving 11q13 by cytogenetic analysis, genomic CCND1 amplification by differential PCR and FISH, and cyclin D1 expression on the mRNA and protein level by differential RT-PCR and immunohistochemistry, respectively. CCND1 amplification, observed in 11 of 32 (34%) tumours, resulted in overexpression of cyclin D1 on the mRNA and/or protein level, in 3 cases in association with chromosomal translocations. In cytogenetic analysis, 4 tumours had hsr(11)(q13), all of which showed CCND1 amplification and cyclin D1 overexpression. Overexpression of cyclin D1 was detected at the mRNA level in 23 tumours (72%) and on the protein level in 25 tumours (78%). In one case a translocation was seen together with cyclin D1 overexpression on the mRNA level, without any cytogenetic or molecular signs of amplification. Furthermore, cases with cyclin D1 overexpression were frequently observed in the absence of any genomic rearrangement. We conclude that, besides amplifications, chromosomal translocations and other transcriptional or translational regulatory mechanisms are involved in CCND1 deregulation.
  • Åkervall, Jan, et al. (författare)
  • Cyclin D1 overexpression versus response to induction chemotherapy in squamous cell carcinoma of the head and neck--preliminary report
  • 2001
  • Ingår i: Acta Oncologica. - Taylor & Francis. - 1651-226X. ; 40:4, s. 505-511
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this study was to investigate whether there is an association between overexpression of cyclin D1 and response to therapy. Immunohistochemical overexpression of cyclin D1 was determined in paraffin-embedded specimens from diagnostic biopsies of 89 primary cases of squamous cell carcinoma of the head and neck (SCCHN), using a polyclonal antiserum. The tumor response rates were estimated after curative treatment (i.e. surgery and/or radiotherapy and/or chemotherapy). Patients whose tumors were overexpressing cyclin D1 showed complete or partial response to neoadjuvant chemotherapy with cisplatin/5-FU. In addition, a majority of cyclin D1 negative tumors did not respond at all to this treatment (p = 0.02, Fisher's exact test). This study indicates that immunohistochemical assessment of cyclin D1 expression in SCCHN could be a new predictive marker to select a subgroup of patients that will benefit from neoadjuvant chemotherapy.
  • Åkervall, Jan, et al. (författare)
  • Genetic and expression profiles of squamous cell carcinoma of the head and neck correlate with cisplatin sensitivity and resistance in cell lines and patients
  • 2004
  • Ingår i: Clinical Cancer Research. - American Association for Cancer Research. - 1078-0432. ; 10:24, s. 8204-8213
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: The choice of treatment for squamous cell carcinoma of the head and neck (SCCHN) is still primarily based on the tumor-node-metastasis classification. However, it is reasonable to believe that biological profiles of SCCHN may be independently associated with response to therapy. The aim of the present study was to examine genetic changes and gene expression profiles that might correlate with sensitivity to cisplatin [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay] in 10 SCCHN cell lines. Experimental Design: Five cisplatin-sensitive and five cisplatin-resistant cell lines [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay] were studied by comparative genomic hybridization, spectral karyotyping, and cDNA microarray analysis (21,632 sequence-validated human cDNA; confirmation by reverse transcriptase-PCR for selected genes). For the MET proto-oncogene, which showed low expression in the chemosensitive cell lines, we did immunohistochemical staining on SCCHN of 29 patients who received induction chemotherapy. Results: The five cisplatin-resistant cell lines showed significantly more genetic imbalances (regions of loss and amplification) and chromosomal abnormalities by comparative genomic hybridization and spectral karyotyping, respectively, than did the five cisplatin-sensitive cell lines. Microarray studies identified similar to60 genes that clearly distinguish between the two groups of cell lines. Some of these genes are known to be involved in tumor progression, metastasis, and drug resistance. We identified low expression of c-met (immunohistochemistry) as a predictive factor for complete response in nondiploid tumors (P = 0.026). Conclusions: We conclude that cisplatin sensitivity and resistance are related to distinctive differences in the genetic and expression profiles in individual SCCHN tumor cell lines and in SCCHN patients. The genes we have identified may serve as potential targets for novel treatment strategies.
  • Åkervall, Jan, et al. (författare)
  • The gene ratios c-MYC : Cyclin-dependent kinase (CDK)N2A and CCND1 : CDKN2A correlate with poor prognosis in squamous cell carcinoma of the head and neck
  • 2003
  • Ingår i: Clinical Cancer Research. - American Association for Cancer Research. - 1078-0432. ; 9:5, s. 1750-1755
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: Tumor-Node-Metastasis classification does not fully predict outcome of treatment and prognosis in patients with squamous cell carcinoma of the head and neck. Different biomarkers have been suggested to yield additional prognostic information, but no single marker has thus far been introduced in the clinic. The objective of the present study was to analyze the copy number of the frequently amplified oncogenes CCND1 and c-MYC in relation to the commonly deleted tumor suppressor gene cyclin-dependent kinase (CDK)N2A (p16) to enhance the clinical significance. Experimental design: Extracted DNA from diagnostic biopsies of 78 untreated patients were analyzed by real-time PCR with specific primers for c-MYC, CCND1, and CDKN2A. Gene copy number ratios were calculated by dividing the copy number of c-MYC or CCND1 with CDKN2A. Ratios > 2 were defined as enhanced. These data were related to disease-free interval and disease-specific survival. Results: Enhanced gene ratio of c-MYC:CDKN2A was detected in 35 of 78 (45%) and enhanced ratio of CCND1: CDKN2A in 36 of 78 (46%) of the cases. The c-MYC: CDKN2A and CCND1:CDKN2A ratios correlated with disease-specific survival with respect to death (P = 0.042 and 0.049, respectively; Log-rank test). Furthermore, enhancement of c-MYC:CDKN2A was associated with a shorter disease-free interval as marked by the development of recurrences or metastases (P = 0.014; Log-rank test). Conclusions: We conclude that CCND1 and/or c-MYC amplification, when combined with CDKN2A deletion, yield additional prognostic information as compared with analysis of single genetic aberrations. These gene ratios, as analyzed by a sensitive method like real-time PCR on diagnostic biopsies, might help clinicians to individualize the treatment of squamous cell carcinoma of the head and neck as they reflect the biological properties of the tumors. This could be used as an adjunct to the Tumor-Node-Metastasis classification system.
  • Öberg, Åke, 1954-, et al. (författare)
  • Detection of occult tumour cells in lymph nodes of colorectal cancer patients using real-time quantitative RT-PCR for CEA and CK20 mRNAS
  • 2004
  • Ingår i: International Journal of Cancer. - Geneve : International union against cancer. - 0020-7136. ; 111:1, s. 101-110
  • Tidskriftsartikel (refereegranskat)abstract
    • The purpose of our study was to develop specific, sensitive, objective assays for early detection of disseminated tumour cells in patients with colorectal cancer (CRC). Carcinoembryonic antigen (CEA) and cytokeratin 20 (CK20) were chosen as markers because they are selectively expressed in epithelial cells with maintained expression in CRC. Real-time quantitative RT-PCR assays with RNA copy standards were constructed. Regional lymph nodes were collected from patients with CRC (n = 51) and benign intestinal disease (n = 10). Results were compared to routine histopathology and anti-CEA immunohistochemistry. Lymph node levels of CEA and CK20 mRNA correlated strongly (p < 0.0001, r = 0.8). Lymph nodes from non-CRC patients had <0.01 CEA and <0.001 CK20 mRNA copies/18S rRNA unit. Lymph nodes from 3/6 Dukes' A, 17/26 Dukes' B, 10/10 Dukes' C and 7/9 Dukes' D patients had CEA mRNA levels above cut-off. Corresponding figures for CK20 mRNA were 3/6, 10/26, 9/10 and 5/9, respectively. CEA mRNA levels varied from 0.001 to 100 copies/18S rRNA unit in Dukes' A and B, and 50% of the Dukes' B patients had CEA mRNA levels within the range of Dukes' C patients. Three Dukes' B patients have died from CRC or developed distant metastases. All 3 had high CEA and CK20 mRNA levels. Determination of mRNA was superior to immunohistochemistry in showing CEA expression in lymph nodes. The present qRT-PCR assay for CEA mRNA seems to be a superior tool to identify individuals with disseminated tumour cells. Future extended studies will establish the clinically most relevant cut-off level.
  • Öhd, John, et al. (författare)
  • Do leukotrienes increase cell viability in human intestinal epithelial cells?
  • 2002
  • Ingår i: Eicosanoids and Other Bioactive Lipids in Cancer, Inflammation, and Radiation Injury, 5 (Advances in Experimental Medicine and Biology). - Springer. - 0065-2598. - 978-0-306-47283-1 ; 507, s. 193-198
  • Bokkapitel (övrigt vetenskapligt)abstract
    • In this preliminary report we present data showing that leukotrienes increase the baseline cell viability in human intestinal epithelial cells and that LTB4 partially reverses the morphological hallmarks of non-necrotic cell death induced by the COX-2 specific inhibitor NS-398. The proposed signaling mechanisms regulating these events are summarized in fig. 3. Please view the work on LT signal transduction in these cells by Thodeti et al. in this volume.
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