| 1. |
- Svensson, Karin, et al.
(författare)
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A protein kinase Cbeta inhibitor attenuates multidrug resistance of neuroblastoma cells.
- 2003
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Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 3:1, s. 10-10
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The acquisition of drug resistance is a major reason for poor outcome of neuroblastoma. Protein kinase C (PKC) has been suggested to influence drug resistance in cancer cells. The aim of this study was to elucidate whether inhibition of PKCbeta isoforms influences drug-resistance of neuroblastoma cells. METHODS: The effect of the PKCbeta inhibitor LY379196 on the growth-suppressing effects of different chemotherapeutics on neuroblastoma cells was analyzed with MTT assays. The effect of LY379196 on the accumulation of [3H]vincristine was also investigated RESULTS: The PKCbeta inhibitor LY379196 suppressed the growth of three neuroblastoma cell lines. LY379196 also augmented the growth-suppressive effect of doxorubicin, etoposide, paclitaxel, and vincristine, but not of carboplatin. The effect was most marked for vincristine and for the cell-line (SK-N-BE(2)) that was least sensitive to vincristine. No effect was observed on the non-resistant IMR-32 cells. Two other PKC inhibitors, Go6976 and GF109203X, also enhanced the vincristine effect. The PKC inhibitors caused an increased accumulation of [3H]vincristine in SK-N-BE(2) cells. CONCLUSIONS: This indicates that inhibition of PKCbeta could attenuate multidrug resistance in neuroblastoma cells by augmenting the levels of natural product anticancer drugs in resistant cells.
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| 2. |
- Lagergren, Anna, et al.
(författare)
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Neuroblastoma and pre-B lymphoma cells share expression of key transcription factors but display tissue restricted target gene expression
- 2004
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Ingår i: BMC Cancer. - : BioMed Central. - 1471-2407 .- 1471-2407. ; 4:80
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Tidskriftsartikel (refereegranskat)abstract
- Background: Transcription factors are frequently involved in the process of cellular transformation, and many malignancies are characterized by a distinct genetic event affecting a specific transcription factor. This probably reflects a tissue specific ability of transcription factors to contribute to the generation of cancer but very little is known about the precise mechanisms that governs these restricted effects. Methods: To investigate this selectivity in target gene activation we compared the overall gene expression patterns by micro-array analysis and expression of target genes for the transcription factor EBF in lymphoma and neuroblastoma cells by RT-PCR. The presence of transcription factors in the different model cell lines was further investigated by EMSA analysis. Results: In pre-B cells mb-1 and CD19 are regulate by EBF-1 in collaboration with Pax-5 and E-proteins. We here show that neuroblastoma cells express these three, for B cell development crucial transcription factors, but nevertheless fail to express detectable levels of their known target genes. Expression of mb-1 could, however, be induced in neuroblastoma cells after disruption of the chromatin structure by treatment with 5-azacytidine and Trichostatin A. Conclusion: These data suggest that transcription factors are able to selectively activate target genes in different tissues and that chromatin structure plays a key role in the regulation of this activity.
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| 3. |
- Olsson, H, et al.
(författare)
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Male gynecomastia and risk for malignant tumours--a cohort study
- 2002
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Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 2, s. 26-26
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Men with gynecomastia may suffer from absolute or relative estrogen excess and their risk of different malignancies may be increased. We tested whether men with gynecomastia were at greater risk of developing cancer.METHODS: A cohort was formed of all the men having a histopathological diagnosis of gynecomastia at the Department of Pathology, University of Lund, following an operation for either uni- or bilateral breast enlargement between 1970-1979. All possible causes of gynecomastia were accepted, such as endogenous or exogenous hormonal exposure as well as cases of unknown etiology. Prior to diagnosis of gynecomastia eight men had a diagnosis of prostate carcinoma, two men a diagnosis of unilateral breast cancer and one had Hodgkin's disease. These patients were included in the analyses. The final cohort of 446 men was matched to the Swedish Cancer Registry, Death Registry and General Population Registry.RESULTS: At the end of the follow up in December 1999, the cohort constituted 8375.2 person years of follow-up time. A total of 68 malignancies versus 66.07 expected were observed; SIR = 1.03 (95% CI 0.80-1.30). A significantly increased risk for testicular cancer; SIR = 5.82 (95% CI 1.20-17.00) and squamous cell carcinoma of the skin; SIR = 3.21 (95% CI 1.71-5.48) were noted. The increased risk appeared after 2 years of follow-up. A non-significantly increased risk for esophageal cancer was also seen while no new cases of male breast cancer were observed. However, in the prospective cohort, diagnostic operations for gynecomastia may substantially have reduced this riskCONCLUSIONS: There is a significant increased risk of testicular cancer and squamous cell carcinoma of the skin in men who have been operated on for gynecomastia.
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| 4. |
- Rydholm, Anders, et al.
(författare)
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Should tumor depth be included in prognostication of soft tissue sarcoma?
- 2003
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Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Most staging systems for soft tissue sarcoma are based on histologic malignancy-grade, tumor size and tumor depth. These factors are generally dichotomized, size at 5 cm. We believe it is unlikely that tumor depth per se should influence a tumor's metastatic capability. Therefore we hypothesized that the unfavourable prognostic importance of depth could be explained by the close association between size and depth, deep-seated tumors on average being larger than the superficial ones. When tumor size is dichotomized, this effect should be most pronounced in the large size (>5 cm) group in which the size span is larger. METHODS: We analyzed the associations between tumor size and depth and the prognostic importance of grade, size and depth in a population-based series of 490 adult patients with soft tissue sarcoma of the extremity or trunk wall with complete, 4.5 years minimum, follow-up. RESULTS: Multivariate analysis showed no major prognostic effect of tumor depth when grade and size were taken into account. The mean size of small tumors was the same whether superficial or deep but the mean size of large and deep-seated tumors were one third larger than that of large but superficial tumors. Tumor depth influenced the prognosis in the subset of high-grade and large tumors. In this subset deep-seated tumors had poorer survival rate than superficial tumors, which could be explained by the larger mean size of the deep-seated tumors. CONCLUSION: Most of the prognostic value of tumor depth in soft tissue sarcomas of the extremity or trunk wall can be explained by the association between tumor size and depth.
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| 5. |
- Elmula, Imad, et al.
(författare)
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Chromosomal aberrations in benign and malignant Bilharzia-associated bladder lesions analyzed by comparative genomic hybridization.
- 2002
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Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 2:5
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Bilharzia-associated bladder cancer (BAC) is a major health problem in countries where urinary schistosomiasis is endemic. Characterization of the genetic alterations in this cancer might enhance our understanding of the pathogenic mechanisms of the disease but, in contrast to nonbilharzia bladder cancer, BAC has rarely been the object of such scrutiny. In the present study, we aimed to characterize chromosomal imbalances in benign and malignant post-bilharzial lesions, and to determine whether their unique etiology yields a distinct cytogenetic profile as compared to chemically induced bladder tumors. METHODS: DNAs from 20 archival paraffin-embedded post-bilharzial bladder lesions (6 benign and 14 malignant) obtained from Sudanese patients (12 males and 8 females) with a history of urinary bilharziasis were investigated for chromosomal imbalances using comparative genomic hybridization (CGH). Subsequent FISH analysis with pericentromeric probes was performed on paraffin sections of the same cases to confirm the CGH results. RESULTS: Seven of the 20 lesions (6 carcinomas and one granuloma) showed chromosomal imbalances varying from 1 to 6 changes. The most common chromosomal imbalances detected were losses of 1p21-31, 8p21-pter, and 9p and gain of 19p material, seen in three cases each, including the benign lesion. CONCLUSION: Most of the detected imbalances have been repeatedly reported in non-bilharzial bladder carcinomas, suggesting that the cytogenetic profiles of chemical- and bilharzia-induced carcinomas are largely similar. However, loss of 9p seems to be more ubiquitous in BAC than in bladder cancer in industrialized countries.
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| 8. |
- Olsson, Håkan, et al.
(författare)
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Relation between the rate of tumour cell proliferation and latency time in radiation associated breast cancer.
- 2003
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Ingår i: BMC Cancer. - 1471-2407. ; 3:1, s. 11-11
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Tidskriftsartikel (refereegranskat)abstract
- Background: Patients with possible radiation induced cancer could be used to study if the rate of tumour cell proliferation is related to latency time. Such a finding could help researcher to find time periods when other initiating risk factors operate. Methods: Seventeen women with breast cancer, with a prior history of radiation treatment towards the parts or the whole breast, exclusive of the primary treatment of a breast cancer were identified. Most women had received treatment for benign disorders as hemangiomas, shoulder pain or skin infections. Three patients had been treated with mantle radiation for Hodgkin's disease prior to developing breast cancer. DNA analysis were performed, on remaining tumour tissue after hormone receptor analysis had been done, measuring the fraction of tumour cells in S-phase. Latency time (time between diagnosis and previous radiation treatment) was calculated and related to the S-phase fraction. Results: A significant inverse relationship between latency time and S-phase was found (p < 0.0025), indicating that tumours with a high S-phase had a short latency time and vice versa. Among the possible radiation induced tumours, median S-phase was 14%, comparable with a median latency time of 22 years. Very high S-phase values were associated with short latency times (eg a S-phase of 35% would be compatible with a latency time of 7 years). Conclusion: Our preliminary results indicate that S-phase is related to latency time and that the median latency time maybe as long as 22 years. Our data may also explain why breast cancer is rare before 30 years of age and if patients are diagnosed at early ages, tumours often show high S-phase values and bad prognostic signs. We postulate that these results from radiation induced breast cancer may be used to extrapolate possible latency times in patients with non radiation induced breast tumours in order to isolate possible time periods for research after other initiating events.
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