| 91. |
- Jonsson, Håkan, 1956-, et al.
(författare)
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Service screening with mammography of women aged 50–69 years in Sweden : effects on mortality from breast cancer
- 2001
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Ingår i: Journal of Medical Screening. - : Sage Publications. - 0969-1413 .- 1475-5793. ; 8:3, s. 152-160
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES:To estimate the effect of the population based service screening programme in Sweden on mortality from breast cancer among women aged 50–69. SETTING:In 1986, population based service screening with mammography started in Sweden, and by 1997 screening had been introduced in all counties. Half of the counties invite women from 40 years of age whereas women 50 and older are invited in the other counties. The upper age limit was either 69 or 74. Women in the age group 50–69 years are thus invited to screening in all counties.METHODS:The counties which started with mammographic screening in 1986–87 constituted the study group and were compared with the counties which started in 1993 or later. In 1987 the mean number of women aged 50–69 was 161 986 and 98 608 in the study and control groups, respectively. Refined excess mortality (smoothed with the Lowess method) from breast cancer and refined cause specific mortality from breast cancer were used as effect measures. To adjust for geographical differences in mortality from breast cancer a reference period was used. Allowance was made for two potential biases: (a) inclusion bias implying the inclusion of cases diagnosed before invitation to screening in the first screening round, and (b) lead time bias.RESULTS:After a mean follow up time of 10.6 years since the start of screening and a mean individual follow up time of 8.4 years, a non-significant reduction in refined excess mortality for breast cancer was estimated as relative risk (RR) 0.84 (95% confidence interval (95% CI) 0.67 to 1.05). After adjustment for inclusion and lead time biases the RR was 0.80 (20% reduction). Only 27% of the deaths from breast cancer in the total mortality for women aged 50–79 at death consisted of women aged 50–69 at diagnosis who were diagnosed after the start of screening. This figure has important implications for judgement of the impact of screening on age specific national breast cancer mortalities.CONCLUSIONS:A non-significant reduction in mortality from breast cancer was found in counties performing service screening with mammography in Sweden. Adjustment for possible biases changed the result towards a larger effect of screening. The results do not contradict the effects found in the Swedish randomised mammography trials.
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| 92. |
- Jordhoy, M S, et al.
(författare)
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Quality of life in advanced cancer patients: the impact of sociodemographic and medical characteristics
- 2001
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 1532-1827 .- 0007-0920. ; 85:10, s. 1478-1485
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Tidskriftsartikel (refereegranskat)abstract
- Population-based surveys have shown that health-related quality of life (HRQL) is influenced by patients' characteristics such as age, gender, living situation and diagnoses. The present study explores the impact of such factors on the HRQL of severely ill cancer patients. The study sample included 395 cancer patients who participated in a cluster randomised trial of palliative care. Median survival was 13 weeks. HRQL assessments (using the EORTC QLQ-C30 questionnaire) were compared among subgroups of relevant patients' characteristics (ANOVA), and the significance of individual covariates was explored by multivariate linear regression. Most EORTC QLQ-C30 scores showed minor differences between genders. Higher age was associated with less sleeping disturbance, less pain and better emotional functioning. No positive impact of living with a partner was found. Performance status and/or time from assessment to death were significantly associated with most functioning and symptom scores. We concluded that although the overall impact of sociodemographic characteristics may seem less important to HRQL scores among advanced cancer patients than in general populations, age and gender should be allowed for. Performance status and closeness to death also need to be reported.
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| 93. |
- Jordhoy, Marit S., et al.
(författare)
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Quality of life in palliative cancer care: results from a cluster randomized trial
- 2001
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Ingår i: Journal of Clinical Oncology. - 1527-7755. ; 19:18, s. 3884-3894
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To assess the impact of comprehensive palliative care on patients' quality of life. The intervention was based on cooperation between a palliative medicine unit and the community service and was compared with conventional care. PATIENTS AND METHODS: A cluster randomized trial was carried out, with community health care districts defined as the clusters. Patients from these districts who had malignant disease and survival expectancy between 2 to 9 months were entered onto the trial. The main quality-of-life end points were physical and emotional functioning, pain, and psychologic distress assessed monthly by using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) questionnaire and Impact of Event scale (IES). In total, 235 intervention patients and 199 controls were included. RESULTS: During the initial 4 months of follow-up, the compliance was good (72%) and comparable among treatment groups. No significant differences on any of the quality-of-life scores were found. At later assessments and for scores that were made within 3 months before death, there was also no consistent tendency in favor of any treatment group on the main outcomes or other EORTC QLQ-C30 scales/items. CONCLUSION: A general program of palliative care may be important to ensure flexibility and to meet the needs of terminally ill patients. However, to achieve improvements on a group level of the various dimensions of quality of life, specific interventions directed toward specific symptoms or problems may have to be defined, evaluated, and included in the program.
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| 94. |
- Jönsson, Marzieh, et al.
(författare)
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Repression of Wnt-5a impairs DDR1 phosphorylation and modifies adhesion and migration of mammary cells
- 2001
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Ingår i: Journal of Cell Science. - 0021-9533. ; 114:Pt 11, s. 2043-2053
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Tidskriftsartikel (refereegranskat)abstract
- The Wnt-5a gene encodes a secreted protein that controls several normal processes during embryogenesis and development of adult tissues by as yet unknown mechanisms. Endogenous expression of Wnt-5a mRNA is known to occur in both mouse and human mammary cell lines. To investigate the biological role of Wnt-5a in the human mammary epithelial cell line HB2, we used an antisense approach to repress endogenous expression of Wnt-5a protein. We also generated a cell population that constitutively overexpresses this protein. We found that overexpression of Wnt-5a protein enhanced cell-to-collagen binding and abolished hepatocyte growth factor-stimulated migration of HB2 transfectants through collagen matrices. Conversely, repression of Wnt-5a protein led to cell scattering, impaired cell-collagen interaction and enhanced cell motility. As we were searching for modified collagen receptors in antisense cells, we discovered that the collagen-binding discoidin domain receptor 1 (DDR1) failed to undergo phosphorylation. In reciprocal experiments, phosphorylation of DDR1 was consistently enabled by expression of Wnt-5a-HA protein in non-Wnt-5a-producing MCF-7 breast cancer cells. Activation of the Wnt/beta-catenin signalling pathway did not influence or mimic the Wnt-5a-mediated effect on DDR1 phosphorylation. These data demonstrate that Wnt-5a protein participates in regulation of adhesion to and migration through collagen and is also a co-factor necessary for collagen-induced activation of DDR1 receptors in mammary epithelial cells.
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| 95. |
- Kadar, Lianna
(författare)
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Body Protein and its Change in Patients During Anti-Tumor Treatment
- 2001
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The purpose of this study was to investigate how total body protein and its fraction of body weight (body protein fraction) change in cancer patients during different anti-tumor treatments, and to see if these changes have any clinical significance in the form of prognostic value or correlation with disease course and tumor response. In 84 patients, 28 with lung cancer, 24 with gastrointestinal tumors, 30 with breast cancer, 1 with non-Hodgkin lymphoma and 1 with kidney cancer, the total amount of body nitrogen was measured using an in vivo prompt gamma neutron activation technique. Using the relationship 1 g nitrogen to 6.25 g protein, the amount of total body protein was calculated. The measurements of body protein and body weight were made during the period of radiation, cytostatic or hormone treatment. Each patient was his or her own control. The precision of the method for measurement of body protein was ±5% (1 SD). In patients with lung cancer, we noted a significant correlation between changes in total body protein during radiotherapy and the recurrence-free interval and overall survival. Patients, in whom body protein decreased, had a significantly shorter time to tumor recurrence than those in whom body protein increased or remained constant. In patients with gastrointestinal tumors we noted a significant difference between the changes in body protein fraction in the patients with loco-regional disease and the patients with metastasized disease, in whom the changes were greatest. Finally, in patients with metastasized breast cancer there was no significant correlation between change in body protein fraction and tumor response. The conclusions are that the amount of body protein in cancer patients changes during the disease and anti-tumor treatment. The amount of body protein in patients with lung cancer has a prognostic value, as a decrease of body protein is an indicator of tumor invasion and early metastasis as well as a decreased overall survival. In patients with gastrointestinal tumors a correlation between change in body protein fraction and course of the disease was seen.
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| 96. |
- Koul, Anjila
(författare)
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Molecular Genetic Alterations In Endometrial And Ovarian Cancers
- 2001
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Endometrial cancer is the most common gynecological cancer diagnosed in western countries. Complex atypical hyperplasia (CAH) reflects a state of hyperestrinism and its role as a precursor lesion of this cancer is established. Endometrial cancers arising in association with CAH are reported in women of younger age, with early stage disease, favorable histological types, higher progesterone receptor levels and clinically better survival prognosis. However, the molecular events delineated in these two pathogenetic types are less known. Hereditary nonpolyposis colon cancer is caused by germline mutations in DNA mismatch repair (MMR) genes, and associated mainly with cancer in the colon, while endometrial and ovarian cancer are the most common extracolonic malignancies in these patients. Tumors from mutation carriers are characterized by an microsatellite instability (MSI) phenotype, and a subset of sporadic colon cancer demonstrates MSI and somatic mutations in MMR genes. MSI is also reported in a subset of sporadic endometrial cancers, although without identifiable mutation in MMR genes. In this study, endometrial cancers histologically checked for presence/absence of CAH were analyzed for mutations in the TP53, PTEN, KRAS, B-catenin, CDKN2A, BRCA1, and BRCA2 genes, as well as for their DNA ploidy and MSI. Two thirds of the endometrial tumors included in the study contained mutation in either of the seven genes analyzed, but very few cases with coexisting mutations were recorded, suggesting alternate genetic pathways in tumorigenesis. We found that PTEN, KRAS, B-catenin, and TP53 mutations were present in tumors both with and without CAH. PTEN mutations associated with MSI and DNA diploidy, while TP53 mutations related to DNA nondiploidy. Approximately 90% of all endometrial cancers are diagnosed in surgical stage disease I and II, with a five-year survival of 85% to 70%, respectively. A consensus opinion regarding useful prognostic markers to identify a “high-risk” subset among these patients is, however, lacking. In this study, TP53 alterations (mutation or protein overexpression) correlated to several clinicopathological markers of poor prognosis in endometrial cancer, and decreased progression-free survival in both early and advanced stage disease. However, DNA nondiploidy seemed to be an even better marker of poor prognosis in patients with early stage disease (I-II). The strongest risk factor for ovarian cancer is a positive family history of ovarian or breast cancer. While the majority of familial cases are associated with germline BRCA1 or BRCA2 mutation, the frequency of mutations in cases unselected for family history is still unclear. In the present pilot study of ovarian tumors, we detected a surprisingly high frequency of both germline and somatic BRCA-gene mutations, emphasizing the importance of extended analysis of population-based series of patients to determine the true contribution of these predisposing genes to the overall incidence of ovarian cancer in this population. BRCA-gene mutations strongly associated with a serous/seropapillary histological type. Unexpectedly, BRCA1 mutations were seen in two cases of ovarian cancer with brain metastasis.
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| 97. |
- Koul, Anjila, et al.
(författare)
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Two BRCA1-positive epithelial ovarian tumors with metastases to the central nervous system: a case report
- 2001
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Ingår i: Gynecologic Oncology. - : Elsevier BV. - 1095-6859 .- 0090-8258. ; 80:3, s. 399-402
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Cerebral metastasis secondary to ovarian cancer is a rare phenomenon. While no clear relationship to known prognostic factors is found, others suggest this as a biologically diverse behavior of ovarian cancer. CASES: In a pilot study, 37 invasive epithelial ovarian cancer samples were analyzed to detect the frequency of BRCA1/BRCA2 mutations in the south of Sweden (results published). A retrospective follow-up revealed that 2 of these (2/37; 5.4%) patients developed central nervous system metastases during the course of their disease. Both patients had advanced surgical stage disease at the time of diagnosis, with histopathological serous type tumors that were negative for estrogen and progesterone receptors. One of these patients carried a germline BRCA1 mutation, whereas a somatic BRCA1 mutation was identified in the other patient. CONCLUSIONS: To the best of our knowledge the molecular genetic profile of these tumors is not found in the literature and it is suggested that such analyses could provide some insight for a better understanding of this rare phenomenon.
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| 98. |
- Krüger Hagen, Else
(författare)
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Contrast enhanced transrectal ultrasound of the prostate : An experimental and clinical study
- 2001
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The purpose of this thesis was to evaluate the diagnostic potential of a new ultrasound contrast agent,SonazoidTM, intended for use in patients with suspicion of prostate cancer.The sonographic appearance of normal prostatic vascularity in dogs was evaluated before and after injection of Sonazoid,using different Doppler flow detection modes.The use of Sonazoid significantly improved the visibility of the vascular pattern in normal dog prostate,both with colour and power Doppler imaging.There was a significant difference in the depiction of blood flow in the prostate between the two imaging modalities,showing the power Doppler superior to colour Doppler imaging.The contrast revealed a radial,spoke-like intraprostatic pattern,not seen prior to contrast injection.Different ultrasound imaging modalities were tested in a small group of young healthy male volunteers to evaluate the visibility of the normal prostate blood flow with and without Sonazoid.The ultrasound contrast agent improved the visibility of the normal human prostate vascular anatomy for both colour and power Doppler imaging.Again,the improvement was significantly better for power Doppler than for colour Doppler imaging.Using fundamental B-mode,there was no major difference in the ultrasound appearance of the prost ate vascular it y before and after i njection of Sonazoid.Cont rast dynamic st udies of blood flow wit hi n t he normal gland showed a filling from the periphery towards the centre in all subjects,demonstrating a symmetric, radial vascular pattern.A canine prostate model was used to investigate if Sonazoid,could improve the visualisation of prostatic vessels to better delineate areas on normal and decreased blood flow.Both 2D and 3D power Doppler imaging was performed in this study.The visibility of the prostate blood flow improved significantly following injection of Sonazoid for both 2D and 3D power Doppler imaging.There was,however,no major difference in depicting the vascularity using 2D and 3D imaging.After injection of Sonazoid,a disturbance of the radial vascular pattern and a lack of blood flow symmetry between the two prostate lobes were possible to identify.The added information gained by injection of Sonazoid made it possible to identify areas of decreased blood flow not seen prior to contrast injection.The vascular pattern of lesions,identified with B-mode imaging in patients with suspicion of prostate cancer,was studied,using Sonazoid.Contrast dynamic inflow in the lesions,compared to the adjacent tissue was investigated in the same study.Prostate cancer lesions appeared hypervasuclar prior to ultrasound contrast agent.Three of six cancer lesions changed from hypervascular to marked hypervascular following injection of Sonazoid,a finding that might be interpreted as a higher level of confidence.None of the non-cancer lesions were assessed as hypervascular after Sonazoid injection,a possible increased value of a negative finding.Four of the cancer lesions enhanced earlier compared to the surrounding prostate tissue,following ultrasound contrast injection.The results indicate that changes in vascular architecture,e.g.induction of angiogenesis by tumour cells,can be observed by ultrasonographically determining the inflow pattern of an intravenously injected ultrasound contrast agent.
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| 99. |
- Kölby, Lars, 1963, et al.
(författare)
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A transplantable human carcinoid as model for somatostatin receptor-mediated and amine transporter-mediated radionuclide uptake.
- 2001
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Ingår i: The American journal of pathology. - 0002-9440. ; 158:2, s. 745-55
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Tidskriftsartikel (refereegranskat)abstract
- A human midgut carcinoid tumor was successfully transplanted into nude mice and propagated for five consecutive generations (30 months) with well-preserved phenotype. Tumor cells in nude mice expressed identical neuroendocrine markers as the original tumor, including somatostatin receptors (somatostatin receptors 1 to 5) and vesicular monoamine transporters (VMAT1 and VMAT2). Because of the expression of somatostatin receptors and VMAT1 and VMAT2 the grafted tumors could be visualized scintigraphically using the somatostatin analogue 111In-octreotide and the catecholamine analogue 123I-metaiodobenzylguanidine. The biokinetics of the somatostatin analogue 111In-octreotide in the tumors was studied and showed a high retention 7 days after administration. Cell cultures were re-established from transplanted tumors. Immunocytochemical and ultrastructural studies confirmed the neuroendocrine differentiation. The human origin of transplanted tumor cells was confirmed by cytogenetic and fluorescence it situ hybridization analyses. Spontaneous secretion of serotonin and its metabolite, 5-hydroxyindole acetic acid, from tumor cells was demonstrated. The tumor cells increased their [Ca2+]i in response to beta-adrenoceptor stimulation (isoproterenol) and K+-depolarization. All somatostatin receptor subtypes could be demonstrated in cultured cells. This human transplantable carcinoid tumor, designated GOT1, grafted to nude mice, will give unique possibilities for studies of somatostatin receptor- and VMAT-mediated radionuclide uptake as well as for studies of secretory mechanisms.
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| 100. |
- Ladanyi, Marc, et al.
(författare)
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The der(17)t(X;17)(p11;q25) of human alveolar soft part sarcoma fuses the TFE3 transcription factor gene to ASPL, a novel gene at 17q25
- 2001
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Ingår i: Oncogene. - : Springer Science and Business Media LLC. - 1476-5594 .- 0950-9232. ; 20:1, s. 48-57
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Tidskriftsartikel (refereegranskat)abstract
- Alveolar soft part sarcoma (ASPS) is an unusual tumor with highly characteristic histopathology and ultrastructure, controversial histogenesis, and enigmatic clinical behavior. Recent cytogenetic studies have identified a recurrent der(17) due to a non-reciprocal t(X;17)(p11.2;q25) in this sarcoma. To define the interval containing the Xp11.2 break, we first performed FISH on ASPS cases using YAC probes for OATL1 (Xp11.23) and OATL2 (Xp11.21), and cosmid probes from the intervening genomic region. This localized the breakpoint to a 160 kb interval. The prime candidate within this previously fully sequenced region was TFE3, a transcription factor gene known to be fused to translocation partners on 1 and X in some papillary renal cell carcinomas. Southern blotting using a TFE3 genomic probe identified non-germline bands in several ASPS cases, consistent with rearrangement and possible fusion of TFE3 with a gene on 17q25. Amplification of the 5' portion of cDNAs containing the 3' portion of TFE3 in two different ASPS cases identified a novel sequence, designated ASPL, fused in-frame to TFE3 exon 4 (type 1 fusion) or exon 3 (type 2 fusion). Reverse transcriptase PCR using a forward primer from ASPL and a TFE3 exon 4 reverse primer detected an ASPL-TFE3 fusion transcript in all ASPS cases (12/12: 9 type 1, 3 type 2), establishing the utility of this assay in the diagnosis of ASPS. Using appropriate primers, the reciprocal fusion transcript, TFE3-ASPL, was detected in only one of 12 cases, consistent with the non-reciprocal nature of the translocation in most cases, and supporting ASPL-TFE3 as its oncogenically significant fusion product. ASPL maps to chromosome 17, is ubiquitously expressed, and matches numerous ESTs (Unigene cluster Hs.84128) but no named genes. The ASPL cDNA open reading frame encodes a predicted protein of 476 amino acids that contains within its carboxy-terminal portion of a UBX-like domain that shows significant similarity to predicted proteins of unknown function in several model organisms. The ASPL-TFE3 fusion replaces the N-terminal portion of TFE3 by the fused ASPL sequences, while retaining the TFE3 DNA-binding domain, implicating transcriptional deregulation in the pathogenesis of this tumor, consistent with the biology of several other translocation-associated sarcomas.
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