| 191. |
- Rydén, Lisa, et al.
(författare)
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Decreased angiogenic activity in breast cancer in ever-users of oral contraceptive therapy--preliminary report
- 2003
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Ingår i: Anticancer research. - 1791-7530. ; 23:3C, s. 2875-2878
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Angiogenic activity defined by microvessel density or measurement of vascular endothelial growth factor is a key process under physiological and malignant conditions in steroid hormone responding organs. The aim of this study was to relate microvessel density (MVD) in primary breast cancer to reproductive data and use of exogenous hormones. MATERIAL AND METHODS: MVD was calculated retrospectively in forty-two consecutive tumours and related to clinical, histopathological and gynecological data. RESULTS: Tumours in ever-users of oral contraceptive therapy (OC) had lower MVD (p = 0.002), a finding not explained by smaller tumour size or lower histological grade. There was no influence on MVD by other reproductive data. CONCLUSION: These preliminary data on a supposed interaction between the use of OC and angiogenesis in breast cancer indicate that biological properties in breast tumours may be altered by ever-use of OC, but have to be further explored in an extended number of patients.
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| 192. |
- Ryden, L, et al.
(författare)
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Tumor specific VEGF-A and VEGFR2/KDR protein are co-expressed in breast cancer
- 2003
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Ingår i: Breast Cancer Research and Treatment. - 1573-7217 .- 0167-6806. ; 82:3, s. 147-154
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Tidskriftsartikel (refereegranskat)abstract
- Angiogenesis is a prognostic indicator in primary breast cancer regulated by specific angiogenic factors and their receptors. Vascular endothelial growth factor-A (VEGF-A), so far considered the most important, acts through dimerization of the receptor VEGFR2/KDR within the receptor tyrosine kinase family of VEGF receptors. In order to study the interplay between VEGF-A and VEGFR2/KDR in breast cancer we evaluated their expression by immunohistochemistry in 102 breast cancers organized in a tumor tissue array system allowing semi-quantitative evaluation of cytoplasmatic staining intensity. In addition, VEGF-A(165) was analyzed by an enzyme immuno assay (ELISA) in protein extracts prepared from frozen tissue from 98 of 102 tumors included in the array. Cytoplasmatic staining of VEGF of varying intensity was observed in all samples and correlated with the ELISA results of VEGF content (p=0.007). Interestingly, VEGFR2/KDR expression correlated with VEGF expression using immunohistochemistry, indicating that VEGF and VEGFR2/KDR may be co-expressed in breast cancer. Furthermore, high levels of VEGF-A(165) in the protein extracts was associated with impaired short time survival but not long term survival whereas immunohistochemically assessed VEGF and VEGFR2/KDR were not significantly associated with survival. In summary, immunohistochemically based analysis of VEGF using a tumor tissue array system seems to be a useful method for VEGF quantification in breast cancer here validated using an ELISA based method. The tumor tissue array system enables opportunities of simultaneous analysis of markers engaged in angiogenesis justifying further studies using larger series of tumors.
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| 193. |
- 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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| 194. |
- Salazar, G, et al.
(författare)
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Apoptosis in male germ cells in response to cyclin A1-deficiency and cell cycle arrest
- 2003
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Ingår i: Biochemical Pharmacology. - 0006-2952. ; 66:8, s. 1571-1579
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Tidskriftsartikel (refereegranskat)abstract
- Male mice homozygous for a mutated allele of the cyclin A 1 gene (Ccna 1) are sterile due to a block in cell cycle progression before the first meiotic division. Meiosis arrest in Ccna1(-1-) spermatocytes is associated with desynapsis abnormalities, lowered MPF activity, and apoptosis as evidenced by TUNEL-positive staining. With time, adult testicular tubules exhibit severe degeneration: some tubules in the older animals are almost devoid of germ cells at various stages of spermatogenesis. The mechanisms by which the cells sense the cell cycle arrest and the regulation of the decision to undergo cell death are under investigation. (C) 2003 Elsevier Inc. All rights reserved.
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| 195. |
- Sand-Dejmek, Janna
(författare)
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Role of Wnt-5a in breast cancer
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Breast cancer is one of the most common cancer forms in the industrialized world. Only in Sweden, nearly 6000 women are diagnosed with breast cancer each year and 1/3 of them eventually succumb to the disease. Wnts are a family of genes that have been implicated in many human tumours, so far mainly studied in colorectal cancer where activated Wnt signalling occurs in a vast majority of tumours. Whereas the oncogenic Wnt-1 is the main Wnt protein investigated in breast cancer, very little work has been focused on Wnt-5a, a protein supposedly antagonizing the oncogenic effects of Wnt-1. We found that Wnt-5a protein expression is reduced in many invasive breast carcinomas and that reduced Wnt-5a expression in the primary tumour strongly correlates with an increased risk of metastatic disease and shorter survival. The expression of Wnt-5a protein co-varies with that of Syk, a tyrosine kinase that is lost in up to 30% of invasive breast carcinomas and associated with poor prognosis. Furthermore, patients with tumours expressing both Wnt-5a and Syk had a significantly better prognosis as compared with those displaying loss of either of or both proteins. Despite the co-expression, loss of Wnt-5a and Syk protein appear to be regulated at the translational and transcriptional levels, respectively. In normal breast epithelium, Wnt-5a is important for cell-ECM adhesion and activation of the collagen receptor DDR1. Restitution of Wnt-5a signalling in breast tumour cells confer better adhesion and ability to activate DDR1 as well as a less malignant-looking phenotype. In human breast epithelial cells Wnt-5a activates the canonical b-catenin pathway as well as the non-canonical Ca2+/calmodulin and planar cell polarity (PCP) pathways. The latter involves Src, the RhoGTPase Cdc42 and JNK and was shown to counteract the NFAT activation induced by the Ca2+/calmodulin pathway. The collagen-induced activation of DDR1, which also is Src-dependent, appears to be mediated by the PCP pathway. Wnt-5a signalling is thus involved in the activation of DDR1 as well as in hampering NFAT activity, both of which affect the migratory capacity of tumour cells. Consequently, the increased metastatic potential of breast tumours with low Wnt-5a expression could be due to inactivation of DDR1 or enhanced NFAT activation. The results presented in this thesis thus imply that Wnt-5a contains metastasis-suppressing activity in breast cancer. Depending on the cellular effects through which Wnt-5a mediates its function, reconstitution of Wnt-5a signalling might have future therapeutical implications.
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| 196. |
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| 197. |
- Sandgren, Staffan, et al.
(författare)
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Suramin selectively inhibits carcinoma cell growth that is dependent on extracellular polyamines.
- 2003
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Ingår i: Anticancer research. - 1791-7530. ; 23:2B, s. 1223-1228
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Tidskriftsartikel (refereegranskat)abstract
- Polyamines are necessary for tumour cell growth. Inhibition of endogenous polyamine biosynthesis results in compensatory up-regulation of polyamine uptake. Here, the combined effect of suramin and the polyamine biosynthesis inhibitor alpha-difluoromethylornithine (DFMO) on human carcinoma cell proliferation was studied. Suramin selectively inhibited the growth of tumour cells made dependent on extracellular polyamines by DFMO-treatment. In an animal tumour model, low non-toxic doses of suramin resulted in a 2-fold increase in DFMO tumour growth reduction. Moreover, suramin bound strongly to polyamine-agarose and significantly inhibited polyamine uptake in DFMO-treated cells. Our results indicate that non-toxic doses of suramin augment tumour growth inhibition by DFMO, and that a combination of these well-studied anticancer drugs may represent an additional strategy for cancer treatment.
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| 198. |
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| 199. |
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| 200. |
- Seth, A, et al.
(författare)
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Gene expression profiling of ductal carcinomas in situ and invasive breast tumors
- 2003
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Ingår i: Anticancer research. - 1791-7530. ; 23:3A, s. 2043-2051
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Tidskriftsartikel (refereegranskat)abstract
- Comparative and functional genomics are powerful tools to advance the understanding of the molecular basis of cancer. It is believed that genes are epigenetically regulated and, thus, each tumor type and stage will be characterized by a gene expression fingerprint. In this study we identified genes that are differentially expressed in ductal carcinoma in situ and invasive ductal carcinoma of the breast. To isolate genes that are associated with progression of breast cancer we performed differential display and subtractive cloning procedures using matched RNA from normal and tumor tissue. cDNA microarray analysis generated gene expression profiles typical of the transition front in situ to invasive breast cancer when we used mRAA extracted from a case of low-to intermediate-grade DCIS and a case of high-grade DC1S/IDC. cDNAs from these samples were the probes in a cDNA microarray hybridization to 9183 unique cDAAs representing 8507 genes. Signals from both transcriptomes were obtained for 8083 genes, and the balanced differential expression values between pure DCIS and DCIS/invasive tumors revealed 303 distinct cDNAs with a ratio of > 2. Interferon inducible genes were found to be expressed at the highest level in the pure DCIS sample. Genes most abundantly expressed in the invasive tumor were immunoglobulin heavy constant gamma 3 and calgranulin B. Further analysis of RNA and protein expression in breast tumor cell lines and patient tissue samples revealed that: IGFBP-rP1 is down-regulated in invasive tumors whereas cyclin I protein is regulated by ubiquitination and is associated with ER-negative breast cancers. Conclusion: The known and novel genes discussed here represent targets for molecular characterization during breast cancer development as well as,for designing novel strategies for diagnosis and treatment.
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