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1.
  • Alarco, J A, et al. (författare)
  • Early stages of growth of YBa2Cu3O7− high Tc superconducting films on (001) Y-ZrO2 substrates
  • 1994
  • Ingår i: Journal of Applied Physics. - : AIP Publishing. - 0021-8979 .- 1089-7550. ; 75, s. 3202-3204
  • Tidskriftsartikel (refereegranskat)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. (författare)
  • Neuroendocrine differentiation in male breast carcinomas
  • 1992
  • Ingår i: APMIS. - : Wiley. - 0903-4641 .- 1600-0463. ; 100:7-12, s. 720-726
  • Tidskriftsartikel (refereegranskat)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. (författare)
  • 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
  • Ingår i: Cytometry. - : Wiley. - 0196-4763 .- 1097-0320. ; 13:6, s. 577-585
  • Tidskriftsartikel (refereegranskat)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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5.
  • Borg, Ake, et al. (författare)
  • The Retinoblastoma Gene in Breast Cancer : Allele Loss Is Not Correlated with Loss of Gene Protein Expression
  • 1992
  • Ingår i: Cancer Research. - 0008-5472. ; 52:10, s. 2991-2994
  • Tidskriftsartikel (refereegranskat)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. (författare)
  • c-myc amplification is an independent prognostic factor in postmenopausal breast cancer
  • 1992
  • Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 51:5, s. 687-691
  • Tidskriftsartikel (refereegranskat)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. (författare)
  • Chromosome I alterations in breast cancer : Allelic loss on Ip and Iq Is related to lymphogenic metastases and poor prognosis
  • 1992
  • Ingår i: Genes, Chromosomes and Cancer. - : Wiley. - 1045-2257 .- 1098-2264. ; 5:4, s. 311-320
  • Tidskriftsartikel (refereegranskat)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. (författare)
  • ERBB2 amplification in breast cancer with a high rate of proliferation
  • 1991
  • Ingår i: Oncogene. - 1476-5594. ; 6:1, s. 137-143
  • Tidskriftsartikel (refereegranskat)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. (författare)
  • ERBB2 amplification is associated with tamoxifen resistance in steroid-receptor positive breast cancer
  • 1994
  • Ingår i: Cancer Letters. - : Elsevier BV. - 1872-7980 .- 0304-3835. ; 81:2, s. 137-144
  • Tidskriftsartikel (refereegranskat)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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11.
  • Fernö, Mårten, et al. (författare)
  • Cathepsin D, both a prognostic factor and a predictive factor for the effect of adjuvant tamoxifen in breast cancer. South Sweden Breast Cancer Group
  • 1994
  • Ingår i: European Journal of Cancer. - 1879-0852. ; 30a:14, s. 2042-2048
  • Tidskriftsartikel (refereegranskat)abstract
    • Cathepsin D is a lysosomal protease implicated in cancer metastasis. Its concentration in breast tumours has also been shown to be of prognostic importance, although to what extent this is subject to lymph node status, the use of adjuvant therapy and menopausal status has not been clearly evaluated. At a cut-off level of 45 pmol/mg protein (61% of the 623 samples were classified as high cathepsin D tumours; immunoradiometric assay), we found cathepsin D to be of prognostic importance only among breast cancer patients with lymph node-positive (N+) disease not treated with adjuvant tamoxifen. When the series was stratified according to cathepsin D content of their tumours, progesterone receptor (PgR) status and lymph node involvement, adjuvant tamoxifen was found to have a significant beneficial effect only among patients with N+ and PgR-positive breast cancer whose tumours had a high cathepsin D content.
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12.
  • Fernö, Mårten, et al. (författare)
  • Flow cytometric DNA index and S-phase fraction in breast cancer in relation to other prognostic variables and to clinical outcome
  • 1992
  • Ingår i: Acta Oncologica. - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 31:2, s. 157-165
  • Tidskriftsartikel (refereegranskat)abstract
    • One frequently used classification of flow cytometric DNA ploidy status (diploid versus nondiploid) was compared with a division into seven ploidy classes based on DNA index (DI) and number of cell populations (hypodiploid, diploid, near-hyperdiploid, hyperdiploid, tetraploid, hypertetraploid, and multiploid). The latter ploidy classification showed a better correlation with prognosis and other prognostic factors (i.e., lymph node involvement, estrogen and progesterone receptor status, and S-phase fraction). The improvement in correlation was mainly due to the identification of near-hyperdiploid cases (DI 1.00-1.14) which could be combined with the diploid cases to form a group with favourable prognosis. In contrast to cases with a small increase in DNA content (near-hyperdiploid), those with a small decrease of DNA content (hypodiploid) manifested a more aggressive disease. In multivariate analysis, S-phase fraction (SPF) was a more important prognostic factor than both the improved or the conventional ploidy classification.
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13.
  • Fernö, Mårten, et al. (författare)
  • One or multiple samplings for flow cytometric DNA analyses in breast cancer-prognostic implications?
  • 1992
  • Ingår i: Cytometry. - : Wiley. - 0196-4763 .- 1097-0320. ; 13:3, s. 241-249
  • Tidskriftsartikel (refereegranskat)abstract
    • Flow cytometric assessments of DNA ploidy status and the S-phase fraction (SPF) have been shown to yield prognostic information in breast cancer. The aim of the present investigation was to elucidate the reproducibility of results with regard to tumor DNA heterogeneity, and to ascertain whether the prognostic value of DNA measurements might be enhanced by analyzing two pieces of a tumor instead of one. Agreement with regard to ploidy status (diploid versus non-diploid) was obtained in 90% of cases (71/79) when two adjacent sections of the tumor were investigated, and in 77% of cases (10/13) when four biopsies from different quadrants of the tumor specimen were investigated. The corresponding figures for agreement in SPF (divided into three categories, less than 7.0%, 7.0-11.9%, and greater than or equal to 12%) were 75% (59/79; 2-sample series) and 55% (7/13; 4-biopsy series). The main reason for variance in ploidy results was the difficulties in distinguishing near diploid cell populations. Discrepancies in SPF categories could be explained by minor fluctuations in SPF values near the cut-off levels, or by variance in ploidy status, the fraction of non-diploid nuclei, and background noise due to cell debris. There was a stepwise increase in recurrence rate (RR) among patients with increasing SPF category (RR: 20%, 41%, and 53%). Patients whose SPF categories varied, from low or intermediate in one part of the tumor to high in another, seemed to have a poor prognosis (RR = 57%).(ABSTRACT TRUNCATED AT 250 WORDS)
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14.
  • Jernström, Helena, et al. (författare)
  • Suppression of plasma insulin-like growth factor-1 levels in healthy, nulliparous, young women using low dose oral contraceptives
  • 1994
  • Ingår i: Gynecologic and Obstetric Investigation. - 1423-002X. ; 38:4, s. 261-265
  • Tidskriftsartikel (refereegranskat)abstract
    • Insulin-like growth factor-1 (IGF-1) levels were analyzed in 43 healthy, nulliparous women aged 19-25 years. Blood samples were drawn in a standardized way in follicular and luteal phases, for present users during cycle days 5-10 and 18-23, respectively. In each women, absolute levels and a difference in p-IGF-1 levels between the two menstrual cycle phases (delta IGF-1) were related to oral contraceptive (OC) use, height, weight, age, gonadotropin and serum sexual hormone binding globulin (s-SHBG) levels. In the follicular phase and cycle days 5-10, absolute values of p-IGF-1 did not significantly differ between present, former and never users of OCs, in contrast to a significant difference (p = 0.0013) in the luteal phase and cycle days 18-23 between present users and never users, after adjustment for age. delta IGF-1 was significantly negatively correlated to present OC use, compared with nonusers (p = 0.0002). delta IGF-1 did not significantly differ between former and never users. While height and weight were not significantly related to delta IGF-1, there was a significant negative correlation between age and delta IGF-1 (p = 0.05). Also, s-SHBG and p-IGF-1 were significantly negatively related in the luteal phase and cycle days 18-23 after adjustment for age (p = 0.006), although this relationship disappeared after adjustment for present OC use.
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15.
  • Johansson, L G, et al. (författare)
  • Preparation and properties of Tl2Ba2CaCu2O8 thin films
  • 1994
  • Ingår i: Journal of Superconductivity. - 0896-1107 .- 1572-9605. ; 7:4, s. 767-771
  • Tidskriftsartikel (refereegranskat)abstract
    • Anex situ process has been developed to produce thin superconducting Tl2Ba2CaCu2O8 films. The properties of films grown on different substrates using different annealing regimes were studied. Critical temperatures of 103–107 K were measured on films prepared in a broad range of annealing temperatures on SrTiO3, LaAlO3, and Y-ZrO2 substrates. A critical current density,J c, of 2×106 A/cm2 at 77 K was measured on LaAlO3. Film morphology was studied by SEM, AFM, and STM.  
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17.
  • Maraste, Rauni, et al. (författare)
  • Anxiety and depression in breast cancer patients at start of adjuvant radiotherapy : Relations to age and type of surgery
  • 1992
  • Ingår i: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 31:6, s. 641-643
  • Tidskriftsartikel (refereegranskat)abstract
    • Using a self-report questionnaire, the Hospital Anxiety and Depression (HAD) scale, feelings of anxiety and depression were assessed in 133 breast cancer patients referred for adjuvant radiotherapy following surgical treatment. Eighteen patients (14% had scores indicating morbid anxiety. Significant depression was recorded for only 2 patients (1.5% Severe anxiety was recorded for 10 out of 54 mastectomized patients (19% and for 8 out of 79 patients treated with breast conserving surgery (10% The difference was not significant (p = 0.13). In a subgroup aged 50-59 years, morbid anxiety was significantly more common among mastectomized patients than among patients operated conservatively, 4 out of 9 (44% vs. 1 out of 23 (4% (p = 0.01). Such a pattern was not discernable in the patients <50 years of age or those ≥ 60 years old. The results suggest that, at start of adjuvant radiotherapy, emotional distress is characterized by anxiety rather than depression and the risk of morbid anxiety is especially large for mastectomized women in their fifties.
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18.
  • Måsbäck, Anna, et al. (författare)
  • Cutaneous malignant melanoma in South Sweden 1965, 1975, and 1985. A histopathologic review
  • 1994
  • Ingår i: Cancer. - 0008-543X. ; 73:6, s. 1625-1630
  • Tidskriftsartikel (refereegranskat)abstract
    • Background. There is an increase in the incidence of cutaneous malignant melanoma (CMM) among white people throughout the world. In Sweden, a fivefold increase has been recorded since 1960, but the mortality is rising at a much lower rate. Tumor thickness is the single most important prognostic factor for primary melanoma. This study aimed to clarify whether the thickness of the tumor in invasive CMM decreased during the period 1965–1985. Methods. This population‐based study identified 574 cases of CMM, both invasive and noninvasive, in the South Swedish Health Care Region in 1965, 1975, and 1985. Twenty‐six cases were excluded because the collection or evaluation of the material was not possible. The remaining 548 cases were reviewed histopathologically, and a diagnosis of invasive CMM was rejected in 71 cases. Eventually, 467 cases of invasive melanoma remained in our study (70 in 1965, 124 in 1975, and 273 in 1985). The level of invasion, tumor thickness, regression, ulceration, presence of inflammatory cells, benign naevus cells, and the site of presentation were studied. Results. The study found neither a significant decrease of tumor thickness of invasive CMM nor changes in the level of invasion or proportion of ulcerated melanoma. A significantly higher proportion of melanoma tumors containing benign naevus cells was seen throughout the years (P < 0.05). Women had significantly fewer inflammatory cells in their tumors than did men (P < 0.01). As expected, the anatomical site of presentation showed a significant sex‐related difference, with more tumors on the legs of female patients and more on the trunk of male patients (P < 0.001). Conclusions. There is a divergence between the rapidly increasing incidence and the slower increase in mortality of CMM. This cannot be explained by a removal of the melanoma at a thinner thickness. Differences between the sexes according to the tumor site and the increasing rate of CMM containing benign naevus cells could implicate changes in the tumor biology. Public education in Sweden concerning ultraviolet radiation and the connection with melanoma is fairly new and might not have any influence on this time period. Additional investigation is needed to clarify this matter.
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19.
  • Nilsson, Håkan, et al. (författare)
  • Pharyngeal constrictor paresis: an indicator of neurologic disease?
  • 1993
  • Ingår i: Dysphagia. - 1432-0460. ; 8:3, s. 239-243
  • Tidskriftsartikel (refereegranskat)abstract
    • Pharyngeal constrictor paresis (PHCP) is sometimes found in videoradiography of the swallowing act in patients complaining of dysphagia. Ten patients with PHCP and 10 dysphagic, age- and sex-matched controls with normal videoradiography were neurologically evaluated and examined with magnetic resonance imaging (MRI) of the brain and brainstem in order to learn the pathogenetic process behind PHCP. The study revealed 8 PHCP patients and 1 dysphagic control with abnormal clinical neurological findings such as myopathy, cerebrovascular disease, or extrapyramidal disease. The neurological examination revealed considerable information of prognostic and therapeutic value in PHCP patients. The MRI was abnormal in 7 PHCP patients and 4 dysphagic controls. However, the findings in MRI were nonspecific but the examination was found to be valuable in selected cases. It is concluded that PHCP is an indicator of neurological disease and accordingly, such patients should be examined by a neurologist to establish the cause of the disease.
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20.
  • Olsson, Håkan, et al. (författare)
  • DNA ploidy assessment of breast milk (colostrum) in primiparous women of different ages
  • 1991
  • Ingår i: Breast Disease. - 0888-6008. ; 4:3, s. 219-222
  • Tidskriftsartikel (refereegranskat)abstract
    • Recent studies on breast cancer risk factors suggest that nursing may have a protective effect. The mechanism behind this is unknown. To investigate whether removal of tumorigenic epithelial cells in breast milk contributes to the reduced risk of developing breast cancer, DNA ploidy of cells in colostrum breast milk from 200 primiparous women was studied with flow cytometry. No woman displayed an abnormal DNA content of the shed epithelium in the milk. Although it cannot be excluded that tumor cells with a near-diploid DNA content are present, our results suggest that early shedding of a large clone of transformed aneuploid epithelium is not a common event and that the protective effect of nursing on breast cancer risk is due to other mechanisms, e.g., hormonal changes in the breast.
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21.
  • Olsson, Håkan, et al. (författare)
  • HER-2/neu and INT2 proto-oncogene amplification in malignant breast tumors in relation to reproductive factors and exposure to exogenous hormones
  • 1991
  • Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 83:20, s. 1483-1487
  • Tidskriftsartikel (refereegranskat)abstract
    • In previous studies in southern Sweden, early use of oral contraceptives has been found to be accompanied by an increased risk of developing premenopausal breast cancer, and the tumors developing in these patients have shown a more aggressive behavior. In the present study, amplification of the proto-oncogenes Her-2/neu (also known as ERBB2) and INT2 was studied in primary tumor specimens from 72 premenopausal women and was related to starting age of oral contraceptive use and other reproductive risk factors. Amplification of Her-2/neu was more common among early oral contraceptive users (i.e., those starting at ≦20 years of age) than among nonusers or late users (odds ratio [OR], 53; 95% confidence interval [CI], 1.6-16.7), whereas INT2 amplification did not differ significantly among those groups (OR, 0.9; 95% CI, 0.1-5.0). The likelihood of INT2 amplification was greater among users of progestins and those with a history of abortions before the first full-term pregnancy (OR, 9.0; 95% CI, 1.3-51.7; and OR, 18.6; 95% CI, 2.2-165.8, respectively). No significant relationships were found between proto-on-cogene amplification and the variables of parity, age at first full-term pregnancy, or late abortion. The increased ORs persisted after adjustment for age at diagnosis and other risk factors. The findings suggest that the higher rate of Her-2/neu amplification among early oral contraceptive users is an effect of the oral contraceptive use per se rather than of the relative youth of the users. Moreover, the relationship between progestin use and early abortion and amplification of the INT2 gene is biologically plausible. [J Natl Cancer Inst 83: 1483-1487, 1991].
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22.
  • Olsson, Håkan, et al. (författare)
  • Proliferation and DNA ploidy in malignant breast tumors in relation to early oral contraceptive use and early abortions
  • 1991
  • Ingår i: Cancer. - 1097-0142. ; 67:5, s. 1285-1290
  • Tidskriftsartikel (refereegranskat)abstract
    • In 175 premenopausal breast cancer patients, a history of oral contraceptive (OC) use before 20 years of age was significantly associated with higher tumor cell proliferative activity, as indicated by a higher S-phase fraction (SPF), and a higher fraction of DNA aneuploid tumors, compared with later or never users (P = 0.05 and p = 0.01, respectively). The higher SPF among early OC users was apparent in patients with aneuploid tumors but not in patients with euploid tumors. Abortions (spontaneous or induced) before the first full-term pregnancy also were associated with a higher SPF compared with other young patients with breast cancer (P = 0.03). Adjusting for parity and abortions or OC use, respectively, an early OC use was associated with a 43% higher SPF and early abortions were associated with 49% higher SPF. Younger patients had a higher SPF and a higher frequency of aneuploid tumors, but this was found to be because the users of OC had a lower median age at diagnosis. Among never users, no significant age relationship was seen for SPF or the frequency of aneuploidy. For the DNA analyses there is a selection of patients with breast cancer with larger tumors, and therefore the conclusions drawn in this article may not be generalizable to patients with smaller primary tumors, e.g., cases diagnosed at breast cancer screening. The higher tumor proliferative activity and frequency of aneuploidy in early OC users are in line with previously reported findings of worse prognostic indicators and a worse survival in early users of OC compared with other young women with breast cancer.
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23.
  • Olsson, Håkan, et al. (författare)
  • Reduced cancer morbidity and mortality in a prospective cohort of women with distal forearm fractures
  • 1992
  • Ingår i: American Journal of Epidemiology. - : Oxford University Press (OUP). - 0002-9262 .- 1476-6256. ; 136:4, s. 422-427
  • Tidskriftsartikel (refereegranskat)abstract
    • At the Department of Orthopedics of University Hospital, Lund, Sweden, cancer incidence and overall and cause-specific mortality were studied in a prospective cohort of 677 women who had experienced a fracture of the distal forearm in 1974 or 1975. The women were followed through population-based population, cancer, and death registries in southern Sweden. There was a significant reduction In overall cancer incidence (66 cases observed vs. 90.21 expected), breast cancer incidence (11 cases observed vs. 20.31 cases expected), and incidence of tumors of the female genital tract (5 cases observed vs. 11.84 expected). Overall mortality was also reduced (146 cases observed vs. 191.69 cases expected), and rates of death from circulatory disease (79 cases observed vs. 111.49 expected) and malignant tumors (30 cases observed vs. 40.41 expected) were both tower than expected.
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24.
  • Pero, Ronald W., et al. (författare)
  • Elevation of ADP-ribosylation as an indicator of mononuclear leucocyte responsiveness in breast cancer patients treated with tamoxifen
  • 1992
  • Ingår i: European Journal of Cancer. - 0959-8049. ; 28:11, s. 1803-1806
  • Tidskriftsartikel (refereegranskat)abstract
    • 82 women who had had surgery for removal of breast cancer were randomised during the primary care period before initiation of any chemotherapy or radiotherapy into two groups: no drug treatment (n = 40) and 20 mg tamoxifen per day for 2 years (n = 42). Mononuclear leucocyte (MNL) fractions from blood samples were collected during the first 368 days of the study and ADP-ribosylation was quantified. Tamoxifen treatment resulted in a dose-duration increase in ADP-ribosylation. This was true even after adjustment for covariates such as age, smoking habits, oestrogen use, menstruation and tumour size. These data suggest that part of the antitumour effects of tamoxifen treatment in vivo relates to an enhanced immune cell responsiveness, as indicated by the increased MNL ADP-ribosylation.
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25.
  • Sigurdsson, H, et al. (författare)
  • Flow cytometry in primary breast cancer: improving the prognostic value of the fraction of cells in the S-phase by optimal categorisation of cut-off levels
  • 1990
  • Ingår i: British Journal of Cancer. - 1532-1827. ; 62:5, s. 786-790
  • Tidskriftsartikel (refereegranskat)abstract
    • The use of continuous prognostic variables is clinically impractical, and arbitrarily chosen cut-off points can result in a loss of prognostic information. Here we report findings from a study of primary breast cancer, showing how the prognostic value of the fraction of cells in the S-phase of the cell cycle (SPF), as measured by flow cytometry, can be affected by the SPF cut-off level(s) adopted. It was possible to evaluate the SPF in 566 (94%) of 603 consecutive cases where fresh frozen specimens were available in a tumour bank at our department. Clinically, all patients were without distant spread at the time of diagnosis, and the median duration of follow-up was 4 years. Using different survival end-points and chi 2 values for each cut-off level, two optimal cut-off points, at the 7% and 12% levels, were consistently obtained for the SPF. Furthermore, both disease-free survival and the relative risk of recurrence exhibited a non-linear relationship with SPF values; the curves implied that the prognosis was better among patients with SPF values about 2-5% than in patients with lower SPF values (parabolic shape), though the relationship with higher SPF values approached linearity. The non-linearity of the curves is incompatible with the general use of the median SPF as a prognostic cut-off value. An alternative procedure might be to use two cut-off levels, one to distinguish patients with the lowest SPF values (i.e. within the parabolic survival curve) from those with higher values (i.e. with a survival curve approaching linearity), the other to distinguish between patients with intermediate SPF values and those with high values (i.e. within the almost linear part of the survival curve). The 7% and 12% obtained here would be suitable for this purpose. We conclude that prognostic information can be gained by dividing the SPF into three prognostic categories (less than 7.0%, 7.0-11.9% and greater than or equal to 12%), instead of using the median SPF level.
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26.
  • Sigurdsson, H, et al. (författare)
  • Indicators of prognosis in node-negative breast cancer
  • 1990
  • Ingår i: New England Journal of Medicine. - 0028-4793. ; 322:15, s. 1045-1053
  • Tidskriftsartikel (refereegranskat)abstract
    • Measures of the proliferative activity of tumor cells have prognostic value in patients with node-negative breast cancer. We studied 367 women in southern Sweden who had undergone surgical resection for such cancer. Tumor specimens were analyzed with DNA flow cytometry in order to estimate both the DNA content (ploidy) and the fraction of cells in the synthetic phase of the cell cycle (S phase). The median duration of follow-up was four years; 28 percent of the patients received adjuvant therapy, usually with tamoxifen (n = 83). A multivariate analysis based on complete data on 250 patients included the following covariates: age (greater than or equal to 75, 50 to 74, and less than or equal to 49 years), tumor size (less than or equal to 20 vs. greater than 20 mm), concentration of estrogen and progesterone receptors (less than 10 vs. greater than or equal to 10 fmol per milligram of protein), ploidy (diploid vs. nondiploid), and S-phase category (fraction of cells in S phase: less than 7.0 percent, 7.0 to 11.9 percent, and greater than or equal to 12 percent). The S-phase fraction yielded the most prognostic information, followed by progesterone-receptor status and tumor size. A prognostic model based on these three variables identified 37 percent of the patients as constituting a high-risk group with a fourfold increased risk of distant recurrence. In the remaining 63 percent of the patients, the five-year overall survival rate (92 +/- 4 [+/- SE] percent) did not differ from the expected age-adjusted rate for Swedish women. We conclude that a prognostic index that includes indicators of the proliferative activity of tumor cells may be able to identify women with node-negative breast cancer in whom the risk of recurrence is sufficiently low that adjuvant chemotherapy can be avoided.
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27.
  • Söderqvist, Gunnar, et al. (författare)
  • Metabolism of estrone sulfate by normal breast tissue : Influence of menopausal status and oral contraceptives
  • 1994
  • Ingår i: Journal of Steroid Biochemistry and Molecular Biology. - : Elsevier BV. - 0960-0760. ; 48:2-3, s. 221-224
  • Tidskriftsartikel (refereegranskat)abstract
    • The metabolism of [ 3 H]estrone sulfate ([ 3 H]E 1 S) was studied in normal breast tissue from 10 premenopausal women without oral contraceptives (OC), in 12 OC users and in 9 untreated postmenopausal women. [ 3 H]E 1 S was converted into estrone ([ 3 H]E 1 ) and estradiol-17β ([ 3 H]E 2 ) by tissue samples from all three groups of women, with only minor formation of other unconjugated compounds. The rate of [ 3 H]E 2 formation was significantly higher in premenopausal women without OC than in postmenopausal women. Among premenopausal women, OC users had a significantly lower rate of total hydrolysis and of [ 3 H]E 1 formation than non-users. The rate of total hydrolysis of [ 3 H]E 1 S in normal breast tissue from all three groups of women was similar to that in muscle, but the rate of [ 3 H]E 2 formation was ten times higher. Both total hydrolysis rate and rate of [ 3 H]E 2 formation were significantly lower in normal breast tissue than in breast carcinoma and in normal and neoplastic endometrium. The specific ability of normal breast tissue to convert E 1 S into the terminal biologically active estrogen E 2 may be important for estrogenic stimulation of the breast in subjects with low circulating E 2 levels. The lower rate of E 1 formation in OC users may reflect an inhibitory effect of the progestagen compound in such preparations.
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28.
  • van de Beek, Jaap, et al. (författare)
  • MMSE estimation of arrival time with application to ultrasonic signals
  • 1993
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • This paper deals with arrival time estimation of a narrow-band signal disturbed by white gaussian noise. In order to estimate the distance between a transmitting source and a reflecting target an estimator, based on the criterion of minimum mean square error (MMSE), is investigated. The MMSE-estimator is implemented in an experimental ultrasound pulse-echo system, and results of comparative simulations between the MAP-estimator and the MMSE-estimator are given. The results are compared to the theoretical Weiss-Weinstein lower bound. As expected, the MMSE-estimator has smaller mean square error than the MAP-estimator. For high SNRs, however, the mean square error obtained by the MAP-estimator manages to approach that of the MMSE-estimator. Other di®erences between the two estimators are revealed in additional experiments in which the range estimates are used to generate 3-dimensional surface pictures.
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29.
  • Westerdahl, J, et al. (författare)
  • Use of sunbeds or sunlamps and malignant melanoma in southern Sweden
  • 1994
  • Ingår i: American Journal of Epidemiology. - 0002-9262. ; 140:8, s. 9-691
  • Tidskriftsartikel (refereegranskat)abstract
    • In a population-based, matched case-control study from the South Swedish Health Care Region, which has the highest risk for melanoma in Sweden, the relation between the use of sunbeds or sunlamps and malignant melanoma was investigated. Between July 1, 1988, and June 30, 1990, a total of 400 melanoma patients and 640 healthy controls aged 15-75 years answered a comprehensive questionnaire containing different epidemiologic variables. Questions regarding the use of sunbeds or sunlamps were included. The odds ratio for developing malignant melanoma after ever having used sunbeds or sunlamps was 1.3. Considering all age groups, the odds ratio was significantly elevated after exposure more than 10 times a year to sunbeds or sunlamps (odds ratio (OR) = 1.8). When the study was restricted to patients and controls younger than age 30 years because the use of tanning devices is much more common among young persons, the odds ratio was higher (OR = 7.7 for more than 10 times a year vs. none). These findings were independent of constitutional factors and factors regarding sun exposure. A dose-response relation was evident. Furthermore, among melanoma patients in this young age group, the ratio of females to males was significantly higher than in older patients. When different melanoma presentation sites were considered, only lesions of the trunk were significantly associated with sunbed or sunlamp use (OR = 4.2 for more than 10 times a year vs. none).
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