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- Behboudi, Afrouz, 1967, et al.
(författare)
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Detailed chromosomal and radiation hybrid mapping in the proximal part of rat Chromosome 10 and gene order comparison with mouse and human.
- 2002
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Ingår i: Mammalian genome : official journal of the International Mammalian Genome Society. - : Springer Science and Business Media LLC. - 0938-8990 .- 1432-1777. ; 13:6, s. 302-9
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Tidskriftsartikel (refereegranskat)abstract
- The rat provides valuable and sometimes unique models of human complex diseases. To fully exploit the rat models in biomedical research, it is important to have access to detailed knowledge of the rat genome organization as well as its relation to the human genome. Rat Chromosome 10 (RNO10) harbors several important cancer-related genes. Deletions in the proximal part of RNO10 were repeatedly found in a rat model for endometrial cancer. To identify functional and positional candidate genes in the affected region, we used radiation hybrid (RH) mapping and single- and dual-color fluorescence in situ hybridization (FISH) techniques to construct a detailed chromosomal map of the proximal part of RNO10. The regional localization of 14 genes, most of them cancer-related ( Grin2a, Gspt1, Crebbp, Gfer, Tsc2, Tpsb1, Il9r, Il4, Irf1, Csf2, Sparc, Tp53, Thra1, Gh1), and of five microsatellite markers ( D10Mit10, D10Rat42, D10Rat50, D10Rat72, and D10Rat165) was determined on RNO10. For a fifteenth gene, Ppm1b, which had previously been assigned to RNO10, the map position was corrected to RNO6q12-q13.
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- Berg, Gertrud, 1944, et al.
(författare)
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Radioiodine ablation and therapy in differentiated thyroid cancer under stimulation with recombinant human thyroid-stimulating hormone
- 2002
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Ingår i: J Endocrinol Invest. - 0391-4097. ; 25:1, s. 44-52
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Tidskriftsartikel (refereegranskat)abstract
- We investigated whether recombinant human TSH (rhTSH) safely and effectively induces uptake of high-dose 131-iodine (131I) to ablate thyroid remnant or treat disease, in patients with well-differentiated thyroid carcinoma. Eleven consecutive patients unable to tolerate thyroid hormone withdrawal received one im injection of 0.9 mg rhTSH on 2 consecutive days before receiving 4000 MBq (approximately 108 mCi) radioiodine orally. Eight patients received one, and 3 patients 2 courses. Our series comprised 7 women and 4 men (mean age, 78 yr, range: 56-87 yr). Ten patients had undergone total or near-total thyroidectomy up to 19 yr earlier. rhTSH-stimulated single course radioiodine with the intention to ablate thyroid remnant was performed in 3 patients, with following estimation of radioiodine uptake and TG measurements. Of another 8 patients given this treatment palliatively, 5 had radiological, clinical and/or laboratory response, including: 80% decreased pathological uptake between treatment courses; pronounced decrease in bone pain; diminished symptoms; improved physical condition and quality of life; lower serum TG concentration; and/or normalization of TG recovery test. Two patients with small lung metastases on computed tomography had no detectable radioiodine uptake or other response; they also lacked uptake after withdrawal-stimulated radioiodine treatment. Despite being elderly and frail, patients generally tolerated treatment well; rhTSH caused nausea in one patient and transiently increased pain in bone and soft tissue lesions in another. We conclude that rhTSH-stimulated high-dose radioiodine for remnant ablation or tumor treatment is safe, feasible and seemingly effective, enhancing quality of life and offering reasonable palliation in patients with advanced disease.
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- Einbeigi, Zakaria, 1962, et al.
(författare)
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Clustering of individuals with both breast and ovarian cancer--a possible indicator of BRCA founder mutations.
- 2002
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Ingår i: Acta oncologica (Stockholm, Sweden). - 0284-186X. ; 41:2, s. 153-7
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Tidskriftsartikel (refereegranskat)abstract
- In a cohort of 60436 women with a diagnosis of invasive breast carcinoma and known to reside in Sweden in 1960, 321 had a subsequent diagnosis of ovarian carcinoma. Assuming no correlation between the two cancers, one would expect that 191 women would develop ovarian cancer (standardized incidence ratio (SIR) 1.7; 95% confidence interval 1.5-1.9). Women with breast cancer before 40 years of age were at highest risk for developing ovarian cancer (SIR 4.5). Between 40 and 49 years of age, the SIR was 1.9, and at 50 years of age or older, the SIR was 1.3. Most of the excess in ovarian cancer occurred in southern Sweden. The geographic distribution of these cases coincided with the distribution of families with known BRCA1 and BRCA2 gene mutations. These results suggest that genetic factors account for the excess in ovarian cancer that occurs in breast cancer patients and that geographic clustering of patients who have both breast and ovarian cancer may indicate the presence of a BRCA founder mutation.
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- Finizia, Caterina, 1961, et al.
(författare)
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A longitudinal study of the Swedish Self-Evaluation of Communication Experiences after Laryngeal Cancer questionnaire in patients treated for laryngeal cancer
- 2002
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Ingår i: Acta Oncol. ; 41:3, s. 262-8
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Tidskriftsartikel (refereegranskat)abstract
- A prospective longitudinal study was performed to investigate the sensitivity to change over time of the Swedish Self-Evaluation of Communication Experiences after Laryngeal Cancer questionnaire (S-SECEL), addressing communication dysfunction in patients with laryngeal cancer. Twenty-six consecutive patients attending a weekly tumour conference over a period of one year at Sahlgrenska University Hospital were included in the study prior to start of treatment. The patients answered four questionnaire repeatedly in the course of one year: the S-SECEL, the European Organization for Research and Treatment of Cancer (EORTC), the Core Quality of Life Core Questionnaire (QLQ-C30) supplemented by the Head and Neck cancer questionnaire module (QLQ-H&N35), and the Hospital Anxiety and Depression (HAD) scale. In addition, performance status was assessed. The S-SECEL questionnaire was well accepted by the patients, and compliance was satisfactory with a cumulative response rate of 88% at one year, supporting its feasibility in clinical settings. Repeated measures with the S-SECEL over one year demonstrated a significant decrease in voice and speech dysfunction. The correlation pattern over time between the S-SECEL and the EORTC and HAD questionnaires lent support to the construct validity of the S-SECEL and indicated that the questionnaire was sensitive to clinical change. The changes in S-SECEL correlated most strongly with changes in the EORTC QLQ-H&N35 speech scale, moderately with changes in the QLQ-C30 role and emotional functioning and global QoL scales, while the weakest correlations were with changes in physical functioning. The S-SECEL was sensitive to changes in communication dysfunction, with convergent and discriminant validity of longitudinal assessments, and with relevance for the quality of life of patients with laryngeal cancer receiving different treatment modalities.
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- Gómez-Fabre, Pedro M, et al.
(författare)
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Predictions based on the rat-mouse comparative map provide mapping information on over 6000 new rat genes.
- 2002
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Ingår i: Mammalian genome : official journal of the International Mammalian Genome Society. - : Springer Science and Business Media LLC. - 0938-8990 .- 1432-1777. ; 13:4, s. 189-93
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Tidskriftsartikel (refereegranskat)abstract
- For identification of ECS ("evolutionarily conserved segments") between rat and mouse, 893 rat-mouse orthologous gene-pairs were brought together with zoo-FISH analysis. In total, 59 autosomal ECS and 4 X-chromosomal ones were detected. Combining FISH and zoo-FISH data, the segments were anchored on the rat chromosomes, providing an improved comparative map between the two species. Since chromosomal evolution is a slow process, it is reasonable to assume that the genome organization, including gene order, is essentially conserved within the ECS. In this way we assigned tentative subchromosomal map positions to 303 rat genes, for which no regional mapping information was available. Furthermore, the concept of prediction mapping was extended to unmapped rat homologs of genes, which in the mouse are situated inside or in the vicinity of an ECS. For a total of 6669 genes, we predicted a single rat chromosomal position, whereas for another 448 genes we could predict that they were located in one of two possible positions. Thus, our study has increased the number of genes for which there is positional mapping information in the rat almost fivefold.
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- Haugen, Hedda, 1970, et al.
(författare)
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Hyperfractionated-accelerated or conventionally fractionated radiotherapy for early glottic cancer.
- 2002
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Ingår i: International journal of radiation oncology, biology, physics. - 0360-3016. ; 52:1, s. 109-19
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To evaluate the effect of shortening overall treatment time by hyperfractionated-accelerated radiotherapy for T2N(0)M(0) glottic carcinomas. Results for local control and survival were calculated and compared to those for T1N(0)M(0) tumors treated with a once-a-day fractionated schedule. METHODS AND MATERIALS: Between 1990 and 1998, 92 patients with T1N(0)M(0) and 45 patients with T2N(0)M(0) glottic cancers were treated with radical radiotherapy. The T1N(0)M(0) tumors were treated with a once-a-day fractionated schedule lasting 6.5 weeks to a total dose of 62.4 Gy. The T2N(0)M(0) tumors received a split-course hyperfractionated-accelerated treatment over a total of 4.5 weeks to a total dose of 64.6 Gy.Results: The 5-year local control was 85% for T1N(0)M(0) and 88% for T2N(0)M(0), whereas the 5-year locoregional control was 85% for both groups. The 5-year overall survival was 70% and 53% for T1N(0)M(0) and T2N(0)M(0), respectively. No significant statistical difference was found between the two groups for the parameters analyzed. The number of serious late complications was few and comparable for the two groups. CONCLUSIONS: Hyperfractionated-accelerated radiotherapy proved beneficial for T2N(0)M(0) glottic cancer, giving local control rates comparable to those for T1N(0)M(0) tumors.
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| 9. |
- Holmberg, Erik, 1951, et al.
(författare)
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Dose-response relationship for parathyroid adenoma after exposure to ionizing radiation in infancy.
- 2002
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Ingår i: Radiation research. - 0033-7587. ; 158:4, s. 418-23
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Tidskriftsartikel (refereegranskat)abstract
- Several authors have suggested that there is an excess risk of hyperparathyroidism, adenomas or hyperplasia after exposure to ionizing radiation. There is still, however, some uncertainty about this association, because these diseases are often asymptomatic and escape clinical detection if not specially searched for. This study is based on a pooled Swedish cohort of 27,925 persons with skin hemangiomas. The majority received radiation treatment in infancy between 1920 and 1965 in Stockholm and Gothenburg. The mean age at treatment was 6 months and the median thyroid dose was 0.20 Gy (range 0-28.5 Gy). Record linkage with the Swedish Cancer Register for the period 1958-1997 gave 43 cases of parathyroid adenoma in the cohort. Analyses of excess relative risk (ERR) models were performed using Poisson regression methods. Clinical records were scrutinized to determine if the childhood radiation exposure was known (biased cases) at the time of diagnosis. Seven of the cases of parathyroid adenoma were classified as biased cases. The standardized incidence ratio (SIR) was 2.10 (95% confidence interval 1.52-2.82) when all cases were included and 1.76 (95% CI 1.23-2.43) with the biased cases excluded. A linear dose-response model with stratification for sex fitted the data best. The ERR per gray was 3.84 (95% CI 1.56-8.99) with all cases and 1.56 (95% CI 0.36-4.45) with the biased cases excluded. There was a significant difference in the ERR per gray between the two subcohorts, probably because of different diagnostic activity in the regions. Our findings confirm that there is a dose-response relationship for radiation-induced parathyroid adenomas.
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| 10. |
- Horvath, György, 1942, et al.
(författare)
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Function of the exon 7 deletion variant estrogen receptor alpha protein in an estradiol-resistant, tamoxifen-sensitive human endometrial adenocarcinoma grown in nude mice.
- 2002
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Ingår i: Gynecologic oncology. - : Elsevier BV. - 0090-8258. ; 84:2, s. 271-9
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In addition to hormone and DNA binding, interactions, including competition with other proteins, appear to be a critical component of transcriptional regulation by the estrogen receptor alpha (ER(alpha)). In vitro studies suggest that exon deletion (Delta exon) variant forms of ER(alpha) may also play an important role in determining the progression from hormone dependence to hormone independence in receptor positive tumors. METHODS: We investigated the presence of ERalpha mRNA and protein variants and their possible role in a moderately differentiated human endometrial adenocarcinoma grown in nude mice. In addition to wild-type (wt), RT-PCR assay of the tumor revealed the presence of two mRNA variants, a low concentration of Delta5 and a high concentration of Delta7 ER(alpha). We detected wt, Delta7, and Delta5,7 mRNA by sequencing the transcripts after stable transfection of three HeLa cells with either splice variant. The linked in vitro translation/transcription assay of the transfected cells and the Western blot analysis of the original tumor generated both wt (66 kDa) and Delta7 (52 kDa), Delta5,7 (46 kDa) ER(alpha) proteins. RESULTS: Tumor growth was characterized as estradiol and progesterone resistant but tamoxifen sensitive, i.e., neither estradiol nor progesterone treatment altered the growth rate, whereas tamoxifen treatment significantly increased the tumor volume doubling time. Estradiol treatment decreased the wt and increased the Delta7 variant ER(alpha) protein expression significantly in a dose-dependent manner. Tamoxifen treatment, however, increased the expression of both proteins whereas progesterone had no effect. Estradiol treatment did not influence expression of the Delta5,7 variant protein, which increased significantly in the tamoxifen-treated tumors. Gel mobility shift assays revealed that both wt and Delta7 ER(alpha) proteins bind to the consensus DNA sequence, whereas the Delta5,7 variant protein did not. CONCLUSIONS: We conclude that estradiol, tamoxifen, and progesterone regulate wt and variant ER(alpha) mRNA and protein expression separately and differently and that this hormonal regulation probably occurs, via different mechanisms, at the transcriptional or posttranscriptional level. The Delta7 variant ER(alpha) may play a crucial role in the determination of hormone sensitivity and thus in the outcome of hormone treatment of human endometrial adenocarcinomas.
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