| 1. |
- Alarco, J A, et al.
(author)
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Early stages of growth of YBa2Cu3O7− high Tc superconducting films on (001) Y-ZrO2 substrates
- 1994
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In: Journal of Applied Physics. - : AIP Publishing. - 0021-8979 .- 1089-7550. ; 75, s. 3202-3204
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Journal article (peer-reviewed)abstract
- Theearly stages of growth of high quality YBa2Cu3O7− (YBCO) filmsgrown on (001) Y-ZrO2 (YSZ) substrates by pulsed laser depositionhave been studied using a combination of atomic force microscopyand transmission electron microscopy. A one unit cell thick YBCOlayer and relatively large CuO particles formed in the initialstages. Additional YBCO grew on top of the first layerin the form of one or a few unit cellhigh c-axis oriented islands about 30 nm in diameter. Therounded islands subsequently coalesced into faceted domains. Elongated Y2BaCuO5 particlesnucleated after the first layer of YBCO. A highly texturedBaZrO3 layer formed between the YSZ and the YBCO witha cube-on-cube dominant orientation relationship with respect to the YBCOfilm. Journal of Applied Physics is copyrighted by The American Institute of Physics.
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| 2. |
- ALM, PER, et al.
(author)
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Neuroendocrine differentiation in male breast carcinomas
- 1992
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In: APMIS. - : Wiley. - 0903-4641 .- 1600-0463. ; 100:7-12, s. 720-726
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Journal article (peer-reviewed)abstract
- The presence of neuroendocrine differentiation, as expressed by cellular chromogranin immunoreactivity, was investigated in paraffin‐embedded tissue material from 51 consecutive cases of male breast carcinoma. From six of these cases electron microscopic studies were included. Chromogranin‐immunoreactive cells were present in solid cords and delineated tubular structures. Ultrastructurally, dense core secretory granules could be detected. The expression of neuroendocrine differentiation was 45%, which is between two and eight times higher than reported for female breast carcinomas by other investigators. The present findings suggest that male breast carcinoma is an exclusive tumour disease showing both similarities and discrepancies when compared to its female counterpart.
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| 3. |
- Baldetorp, Bo, et al.
(author)
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Image cytometric DNA analysis in human breast cancer analysis may add prognostic information in diploid cases with low S-phase fraction by flow cytometry
- 1992
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In: Cytometry. - : Wiley. - 0196-4763 .- 1097-0320. ; 13:6, s. 577-585
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Journal article (peer-reviewed)abstract
- Measurements of DNA ploidy can be performed either with image cytometry (ICM) or flow cytometry (FCM); both methods provide independent prognostic information in primary breast cancer. The aim of the present investigation was to compare the two methods and to relate the findings to prognosis (median follow-up 42 months). Concordance in ploidy status (diploid, tetraploid, aneuploid) was obtained in 76% of the samples (168/222). When the fraction of S-phase cells (SPF) from FCM analysis was also taken into consideration, four different groups of samples were obtained (Flow I-IV), which were considered to correspond to the Auer classification (Auer I-IV) of DNA histograms obtained from image cytometry. Complete concordance between the two techniques now was 70% (155/222). Samples classified as Flow I (diploid or near-diploid with low SPF) and Auer I had a distant metastasis rate of 3/60 (5%), as compared to 62/154 (40%) for all other combinations of the Flow and Auer classifications taken together. Thus, the only findings of prognostic importance were that some samples were Flow I but not Auer I, or vice versa. These two groups represent 17 (7.7%) and 14 (6.3%), respectively, of the total number of samples, and had frequencies of distant metastasis similar to those of the other high-risk groups, namely, 7/17 and 5/14, respectively. In a multivariate analysis, flow cytometric S-phase value was a stronger prognostic factor than either the Flow and Auer classification. We conclude that when routine FCM DNA analysis is used, diploid or near-diploid samples with a low S-phase value should be reanalyzed with ICM.
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| 4. |
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| 5. |
- Borg, Ake, et al.
(author)
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The Retinoblastoma Gene in Breast Cancer : Allele Loss Is Not Correlated with Loss of Gene Protein Expression
- 1992
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In: Cancer Research. - 0008-5472. ; 52:10, s. 2991-2994
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Journal article (peer-reviewed)abstract
- The significance of the retinoblastoma gene (RB) in the development of human breast cancer remains unclear. In the present study, loss of heterozygosity (LOH) in RB was found in 26% of 90 informative primary breast tumors and was correlated to DNA nondiploidy, a high S-phase fraction, and LOH at chromosome 17pl33. However, allele loss was not associated with loss of RB protein (pRB) expression. Low to absent levels of pRB were found in 15% of 73 immunoblot analyzed tumors, most of which manifested retained heterozygosity in RB. Conversely, tumors exhibiting LOH showed often high pRB expression. Our data suggest that RB may be Involved in the pathogenesis of some breast tumors, as evidenced by the absence of pRB, but that this alteration is acquired by mechanisms other than the unmasking of a recessive mutation by allele loss. LOH in RB may be merely a stochastic event in the unstable genome of aneuploid, rapidly proliferating cells or, alternatively, reflect the presence of an adjacent tumor suppressor gene.
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| 6. |
- Borg, Åke, et al.
(author)
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c-myc amplification is an independent prognostic factor in postmenopausal breast cancer
- 1992
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In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 51:5, s. 687-691
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Journal article (peer-reviewed)abstract
- The c-myc proto-oncogene was analyzed in 311 cases of primary breast cancer, in 8% of which it was found to be amplified, usually at moderately increased copy number (2-5 copies). The adjacent pvt gene was co-amplified with c-myc in all tumors analyzed. C-myc amplification was significantly correlated to a high S-phase fraction and to amplification of the c-erbB-2 proto-oncogene. Weak relationships were found between c-myc amplification and the presence of lymph-node metastasis, advanced stage, DNA non-diploidy and premenopausal status, but not tumor size, estrogen receptor or progesterone receptor status, or int-2 amplification. C-myc amplification, and especially a high gene copy number (greater than 5 copies), was significantly related to early recurrence and death in breast cancer, a relationship seen in both the lymph-node-negative and node-positive subcategories. A particularly strong correlation with poor clinical outcome was seen in postmenopausal patients (p greater than 0.0005), an association which persisted in multivariate survival analysis. We conclude that the activation of c-myc is indeed associated with rapidly growing and progressive breast cancer. Gene amplification, on the other hand, is relatively infrequent and occurs mostly at low copy number, implying that tumors are heterogeneous with respect to cell clones harboring c-myc amplification. An immunohistochemical assessment would more accurately illustrate the importance of c-myc activation in human breast cancer. However, the obvious instability of the c-myc transcript and translate suggests that c-myc is not a suitable prognostic marker for routine purposes.
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| 7. |
- Borg, Åke, et al.
(author)
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Chromosome I alterations in breast cancer : Allelic loss on Ip and Iq Is related to lymphogenic metastases and poor prognosis
- 1992
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In: Genes, Chromosomes and Cancer. - : Wiley. - 1045-2257 .- 1098-2264. ; 5:4, s. 311-320
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Journal article (peer-reviewed)abstract
- The development of human breast cancer is characterized by a variety of genetic alterations, and cytogenetic analyses have documented the consistent involvement of both arms of chromosome I. In the present study, molecular markers detecting restriction fragment length polymorphisms were used in pairwise screening of normal and tumor DNA to determine the frequency of allelic imbalance in breast tumors. Loss of heterozygosity (LOH) in the polymorphic epithelial mucin (PEM or MUCI) gene at 1q21 was found in 16% of 89 informative (constitutionally heterozygous) cases, whereas gain in intensity of one allelic band was more frequent (37%), a total of 47% of cases manifesting either allelic loss or gain. Three additional tumors manifested a structural alteration. Allelic loss or gain in the PEM gene was not associated with other prognostic factors, e.g., tumor size, lymph node status, steroid receptors, DNA ploidy, S phase fraction, protooncogene amplification, histological type, or patient age. However, LOH in the PEM gene was significantly correlated with early disease recurrence (P = 0.006). LOH on 1p was found in 27% of 117 informative cases, using probes for either DIS57 or DIZ2 located at 1p33‐p35 and 1p36, respectively. Somatic allelic imbalance on 1p and 1q seemed to be independent events and not the effect of loss of a whole chromosome 1. LOH on 1 p was significantly correlated to the presence of lymph node metastasis, to larger tumor size, and to DNA nondiploidy, but no correlation was found to disease outcome at this limited duration of follow‐up (median 29 months). ©1992 Wiley‐Liss, Inc.
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| 8. |
- Borg, Åke, et al.
(author)
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ERBB2 amplification in breast cancer with a high rate of proliferation
- 1991
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In: Oncogene. - 1476-5594. ; 6:1, s. 137-143
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Journal article (peer-reviewed)abstract
- The ERBB2 proto-oncogene was studied in 539 invasive primary breast tumors and was found amplified (2- greater than 30 copies) in 19%. Amplification was correlated to most known risk factors, including; large tumor size, lymph node positivity and many tumor involved nodes, advanced stage, low patient age (less than 40 years), non-diploidy and hypertetraploidy, and most significantly (P less than 0.00001) to the absence of steroid receptors and to a high rate of proliferation (flow cytometric determined S phase fraction). ERBB2 amplification was strongly associated (P less than 0.0001) with early recurrence and death in breast cancer among node-positive patients. This connection did not, however, remain in multivariate analyses. No correlations to clinical outcome were seen among node-negative patients. Similarly, non-diploid, but not diploid, amplified tumors were particularly aggressive. Furthermore, ERBB2 amplification was associated with a high rate of proliferation and poor prognosis in steroid receptor positive, but not receptor negative tumors. In progesterone receptor positive breast cancer, amplification was an independent and with node status equally powerful (P less than 0.0001) predictor of poor survival. It is concluded that ERBB2 activity is related to an increased tumor growth rate but not directly to metastasizing ability. Its clinical relevance as a prognostic factor may be in selecting a high risk subgroup of breast cancer, in general considered as being of good prognosis.
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| 9. |
- Borg, Åke, et al.
(author)
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ERBB2 amplification is associated with tamoxifen resistance in steroid-receptor positive breast cancer
- 1994
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In: Cancer Letters. - : Elsevier BV. - 1872-7980 .- 0304-3835. ; 81:2, s. 137-144
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Journal article (peer-reviewed)abstract
- Amplification and overexpression of the ERBB2 (HER-2/neu) oncogene has been implicated as contributing to the development of human breast cancer, and as a predictor of poor survival. In the present non-randomized study of 871 primary invasive breast tumours, ERBB2 activation was significantly correlated to a shorter disease-free and overall survival in the subgroup of patients receiving adjuvant tamoxifen therapy, but not in the untreated group. Further subcategorization demonstrated the relationship to poor prognosis to be confined to lymph node positive and steroid receptor-positive tumours. We suggest that steroid receptor and ERBB2-positive breast tumours are resistant to tamoxifen therapy and, supported by experimental evidence showing an oestrogen receptor dependent up-regulation of ERBB2 expression upon tamoxifen administration, possibly even growth stimulated by the drug.
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| 10. |
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