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Träfflista för sökning "hsv:(MEDICIN OCH HÄLSOVETENSKAP) hsv:(Klinisk medicin) hsv:(Cancer och onkologi) srt2:(2000-2004);srt2:(2000)"

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  • Edgren, M, et al. (författare)
  • Estramustine a radio sensitising agent.
  • 2000
  • Ingår i: Anticancer research. - 0250-7005. ; 20:4, s. 2677-80
  • Tidskriftsartikel (refereegranskat)abstract
    • The present study revealed that estramustine acts as a radio sensitising agent on the human renal cell cancer cell lines, A498 and CAKI-2. In vitro experiments used the Bürker chamber technique. Both cell lines were markedly resistant to external beam irradiation. While pretreatment of the cell cultures with estramustine prior to external beam irradiation revealed an arrest of cell growth in both cell lines. The results of this study suggest that estramustine could be utilised as a radiosensitizing agent. This in turn could open a new method for the management of patients with advanced renal cell carcinoma (RCC).
  • Ejeskär, Katarina, 1969- (författare)
  • Genetic alterations in Scandinavian neuroblastoma tumors
  • 2000
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • The results presented here derive from our efforts to find genes and chromosomal regions of interest in the formation and progression of the childhood tumor neuroblastoma.Neuroblastoma is the most common extracranial solid tumor of childhood. It is a tumor of the postganglionic sympathetic nervous system, and clinically, the hallmark of neuroblastoma is its heterogeneity.In order to characterize chromosomal regions of interest the methods loss of heterozygozity (LOH) studies using PCR-based polymorphic markers, representational difference analysis (RDA), somatic cell hybrid mapping, fluorescent in situ hybridization (FISH), radiation hybrid mapping and physical mapping by construction of a BAC-contig have been used. For mutation analysis of genes the methods single strand conformation polymorphism (SSCP), heteroduplex (HD) and DNA-sequencing have been used, and the expression studies of candidate genes have been performed using RT-PCR.In the Scandinavian neuroblastoma tumor material we have been able to show that deletions of chromosome arm 3p is the second most common deleted chromosomal region (16%) next to 1p (22%). We could also see a difference in clinical outcome between patients with tumors displaying deletion of the entire chromosome 3 versus the ones with tumors displaying deletions of region 3p only. The ones with 3p-deletion have all died of disease whereas the ones with entire chromosome 3 loss are alive and well. We have also characterized a region on chromosome 1, 1p36, shown, by others and us, to be commonly deleted in neuroblastoma tumors. A critical region of app. 25 cM between genetic markers D1S80 and D1S244 could be defined. We have also by using combined LOH-data from both neuroblastoma and germ cell tumors defined a region of common deletion for both tumor types, this region could be defined by markers D1S508 and D1S244 and is app. 5 cM.Also some 1p36 putative tumor suppressor genes, i.e. CDC2L1, TP73 and CORT, have been fine mapped and tested for expression and mutations in neuroblastomas. No evidence for any of them to be the 1p36 neuroblastoma tumor suppressor gene has however been discovered.
  • Ekblad, Lars, et al. (författare)
  • Purification of rabbit lacrimal gland plasma membranes by aqueous two-phase affinity partitioning
  • 2000
  • Ingår i: Journal of Chromatography. B, Biomedical Sciences and Applications. - Elsevier. - 1387-2273. ; 743:1-2, s. 397-401
  • Tidskriftsartikel (refereegranskat)abstract
    • We describe the purification of lacrimal gland plasma membranes by affinity partitioning using a two-phase system containing polyethylene glycol and dextran in which wheat germ agglutinin conjugated to dextran is used as affinity ligand. When partitioning a microsomal fraction, the plasma membrane marker 5'-nucleotidase was obtained in the affinity ligand-containing bottom phase, whereas the endoplasmic reticulum marker NADH-ferricyanide reductase remained in the top phase. The affinity partitioning behaviour of components involved in exocytosis and cellular signalling was also examined.
  • Elmroth, Kerstin, 1970-, et al. (författare)
  • Effect of hypothermic irradiation of the growth characteristics of two human cell lines
  • 2000
  • Ingår i: Anticancer Res. - 0250-7005 (Print). ; 20:5B, s. 3429-33
  • Tidskriftsartikel (refereegranskat)abstract
    • The effect of hypothermic irradiation on the growth characteristics of two human cell lines was investigated. Low temperature (2 degrees C) X-irradiation of MCF-7 cells (2, 3 and 4 Gy) resulted in higher surviving fractions compared to irradiation at 37 degrees C as assessed by the colony forming assay. The ratios for the surviving fraction between the two temperatures were 1.2, 1.5 and 1.7 at 2, 3 and 4 Gy, respectively. Correspondingly, the dose modifying factor was 1.23. The distribution of colony sizes (of those with more than 50 cells) was different with proportionally more small-sized colonies from cells irradiated at 2 degrees C. Colonies from diploid fibroblasts (HS27) were ill-defined and could not be counted. In conclusion, hypothermia during irradiation seems to influence the radioresponse in MCF-7 cells. The growth in multiwell plates of MCF-7 cells and human diploid fibroblasts (HS27) after irradiation with 3 and 4 Gy, respectively, at 2 degrees C or 37 degrees C was assessed by using the crystal violet growth assay. No difference between 2 degrees C or 37 degrees C irradiation was found for either of the two cell lines.
  • Elmroth, Kerstin, 1970-, et al. (författare)
  • Radiation-induced double-strand breaks in mammalian DNA: influence of temperature and DMSO
  • 2000
  • Ingår i: Int J Radiat Biol. - 0955-3002 (Print). ; 76:11, s. 1501-8
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: To investigate the effects of subphysiological irradiation temperature (2 28 degrees C) and the influence of the radical scavenger DMSO on the induction of double-strand breaks (DSB) in chromosomal DNA from a human breast cancer cell line (MCF-7) as well as in intact cells. The rejoining of DSB in cells irradiated at 2 degrees C or 37 degrees C was also investigated. MATERIALS AND METHODS: Agarose plugs with [14C]thymidine labelled MCF-7 cells were lysed in EDTA-NLS-proteinase-K buffer. The plugs containing chromosomal DNA were irradiated with X-rays under different temperatures and scavenging conditions. Intact MCF-7 cells were irradiated in Petri dishes and plugs were made. The cells were then lysed in EDTA-NLS-proteinase-K buffer. The induction of DSB was studied by constant field gel electrophoresis and expressed as DSB/100/Mbp, calculated from the fraction of activity released into the gel. RESULTS: The induction of DSB in chromosomal DNA was reduced by a decrease in temperature. This protective effect of low temperature was inhibited when the DNA was irradiated in the presence of DMSO. No difference was found when intact cells were irradiated at different temperatures. However, the rapid phase of rejoining was slower in cells irradiated at 37 degrees C than at 2 degrees C. CONCLUSIONS: The induction of DSB in naked DNA was reduced by hypothermic irradiation. The temperature had no influence on the induction of DSB in the presence of a high concentration of DMSO, indicating that the temperature effect is mediated via the indirect effects of ionizing radiation. Results are difficult to interpret in intact cells. Rejoining during irradiation at the higher temperature may counteract an increased induction. The difference in rejoining may be interpreted in terms of qualitative differences between breaks induced at the two temperatures.
  • Engarås, Boel, 1949- (författare)
  • Characteristics of tumour markers CEA, CA 50 and CA 242 in serum with reference to colorectal cancer
  • 2000
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • There is no consensus on if and how to conduct colorectal cancer surveillance. Serum levels of tumour markers and especially CEA increase before a recurrence is detected by clinical diagnosis. Second look surgery based on elevated serum levels of CEA has been beneficial for individual patients. Due to inconsistent findings, CEA-measurements after curative surgery hold a low grade of recommendation.The aim of the present study was to identify better surveillance tools using tumour markers for indicating relapsing colorectal cancer. Standard levels and fluctuation in cancer-free individuals in an age group where cancers are likely to occur were unknown, as was the influence of surgery in cancer-free patients undergoing surgery for benign disease and in patients surviving colorectal cancer. The aim was to establish those serum levels of CEA, CA 50 and CA 242. Based on these findings, individual cut-off levels of markers were to be identified. Also levels of CEA and CA 242 in future cancer patients were to be measured.It was found that the 90th percentile (chosen as standard level) of serum levels of CEA, CA 50 and CA 242 were 5,6 ng/ml, U/ml and 25 U/ml respectively. Serum-levels of CEA were higher in smokers and also increased with age. The fluctuation was below 20% for all markers. There was a transient decline in serum levels of CEA after surgery and they had not recovered until one year after the surgical procedure. Patients surviving colorectal cancer had a similar decline. In the post-operative period there was a positive relation between CEA levels and an inverse relation between CA 242 levels and Dukes´ staging in the patients surviving colorectal cancer. With individual cut-off levels all hepatic metastases occurring during the test period (two years after surgery) were indicated by CEA (0-19) months before they were clinically detected. In total twenty-four recurrences were detected during the test period. Twenty-one (88%) were indicated by CEA, eleven by CA 50 (46%) and nineteen (79%) by CA 242 (individual cut-off). Serum levels of CEA and CA 242 were highest close to cancer diagnosis
  • Fernö, Mårten, et al. (författare)
  • Results of two or five years of adjuvant tamoxifen correlated to steroid receptor and S-phase levels
  • 2000
  • Ingår i: Breast Cancer Research and Treatment. - Springer. - 1573-7217. ; 59:1, s. 69-76
  • Tidskriftsartikel (refereegranskat)abstract
    • A Swedish cooperative trial demonstrated that 5 years of adjuvant tamoxifen was more beneficial than 2 years of tamoxifen in the treatment of postmenopausal women with estrogen receptor (ER) positive, early stage, invasive breast cancer. The main aim of the present study was to investigate the importance of progesterone receptor (PgR) and ER concentration levels for patients participating in the trial and still distant recurrence free two years after the primary operation. Subgroup analyses revealed that only patients with ER positive and PgR positive breast cancer had improved distant recurrence free survival (DRFS) by prolonged tamoxifen therapy (p = 0.0016). Patients with ER negative and PgR negative as well as ER positive and PgR negative tumors showed no significant effect of prolonged tamoxifen (p = 0.53 and p = 0.80, respectively). The percentage of ER negative and PgR positive breast cancers was too small (2.2%) for any meaningful subgroup analysis. There was a significant positive trend that the concentration level of PgR (high positive vs. low positive vs. negative) decreased the recurrence rate for those with prolonged therapy. No corresponding pattern was found for the ER content. S-phase fraction did not correlate to the recurrence rate of PgR positive breast cancers. Patients recurring during tamoxifen therapy had receptor negative tumors to a greater extent than those recurring after tamoxifen treatment. In conclusion, prolonged tamoxifen therapy for 5 years instead of 2 years was found to be beneficial for patients with ER positive and PgR positive breast cancer, whereas three extra years of tamoxifen had little or no effect for patients with ER positive but PgR negative tumors as well as for steroid receptor negative patients.
  • Fransson, Per (författare)
  • Quality of life and side effects in patients with localized prostate cancer evaluation with self-assessment questionnaires
  • 2000
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • Localized prostate cancer (LPC) is predominantly a tumor among older men, and few patients will get symptoms from the disease. All methods to treat LPC with a curative intent have different types and degrees of side effects. It is therefore very important to evaluate the side effects thoroughly to make sure that treatment complications will not decrease the quality of life more than the disease would have done. In search for new and better treatments, complications has to be registered and evaluated in relation to quality of life (QOL) for the patients. Few validated self-assessment questionnaires for evaluation of external radiotherapy (EBRT) induced side effects has yet been developed. The present project focus on the development of the PC-specific questionnaire, QUFW94, and evaluation of symptoms in patients treated with EBRT and un-treated (watchful waiting) patients with a LPC.In the newly developed LPC-specific questionnaire a reliability and responsiveness test was performed. Both the inter-rater test and the test-retest show high correlation coefficients (ICC), above 0.60 for all scales. The internal reliability exceeded the lower acceptable limit (Cronbach a >0.70). The questionnaire was proven to be valid for the evaluations of EBRT side effects in LPC patients.Late side effects were evaluated 4 years after treatment in 181 LPC patients, treated with conventional large field EBRT, and compared with 141 age-matched PC disease free men. The most prominent urinary side effects were urgency and leakage which were doubled in the patient group. A ten fold increase was seen in comparison to controls at the most prominent intestinal problems, blood, mucus and leakage. The results support the use 3-D conformai therapy to decrease irradiation dose to the rectum and the bladder and thereby decreased side effects. A prospective additional evaluation 8 years after EBRT did not show any changes in urinary problems between 4 and 8-yr follow-up in the patients or the controls.EBRT of LPC is also accompanied by disturbances in sexual function. These problems were therefore evaluated, 4 years after EBRT, in relation to the function in PC free men. Patients treated with EBRT indicated higher levels of sexual dysfunction than age-matched controls. No erection was reported from 12% of the control subjects, 56% of the patients who had only received radiotherapy (RT) and 87% of the RT+castration (RT+A) patients. The extended evaluation 8 years after EBRT show similar sexual function in all groups.QOL and late side effects/symptoms were evaluated in the first and only randomized trial between RT and deferred treatment (DT) and compared to age-matched controls. QOL was evaluated with the general QOL formula, EORTC's QLQ-C30 (+3), and LPC specific side effects with QUFW94 in 108 randomized patients with LPC 3 years after diagnosis. Social functioning was the only QOL scale where a significant difference was found between the two patient groups and in comparison with the control group. Multivariate regression analysis showed that hematuria, incontinence, mucus, and planning of the daily activities due to intestinal problems caused this decrease in QOL in the RT group. In conclusion, the LPC specific QUFW94 questionnaire was proven to be valid for evaluation of side effects and showed increased intestinal problems in the patients treated with conventional large field EBRT in comparison to untreated LPC patients. No difference in urinary and intestinal late side effects or sexual function was seen between a 4 year vs. 8 year follow-up.
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