| 1. |
- Baldetorp, Bo, et al.
(author)
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Reproducibility in DNA flow cytometric analysis of breast cancer: comparison of 12 laboratories' results for 67 sample homogenates
- 1995
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In: Cytometry. - : Wiley. - 0196-4763 .- 1097-0320. ; 22:2, s. 115-127
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Journal article (peer-reviewed)abstract
- Flow cytometric (FCM) DNA analysis yields information on ploidy status and the S-phase fraction (SPF), variables of prognostic importance in breast cancer. The clinical value of the SPF is currently being evaluated in prospective randomized trials. The widespread use of FCM DNA analysis emphasizes the importance of reproducibility (both intra- and interlaboratory). In this study, 67 nuclear suspensions of breast cancer samples were analyzed by 12 laboratories routinely performing FCM DNA analysis in breast cancer. No general guidelines were imposed; each laboratory used its own standard protocols. For DNA ploidy status (diploid vs. non-diploid), agreement was complete for 79% (53/67) of the samples, compared with 64% (43/67) of samples when tetraploidy was considered [i.e., euploid (diploid+tetraploid) vs. aneuploid (the remaining non-diploid)]. For the SPF, pairwise comparison of the results of all 12 laboratories yielded a mean Spearman's rank correlation of 0.78 (range: 0.54-0.93). For those 39 samples being categorized in low or high SPF by all laboratories, all agreed in 14 samples (36%). Similar patterns were obtained with kappa measures, agreement being good for ploidy status (diploid vs. non-diploid; overall kappa = 0.87 and 0.74 for euploid vs. aneuploid), but moderate for the SPF [overall kappa = 0.47 (for low SPF vs. high SPF vs. "no SPF reported")]. Discrepancies were chiefly attributable to differences in the categorization of the S-phase values, rather than in FCM procedures, other critical differences being in the detection and interpretation of near-diploid and small non-diploid cell populations, the definition of tetraploidy, and the choice and execution of the method used for S-phase estimation. Based on the observations of this study, detailed guidelines for FCM analysis and interpretation of data are proposed in the Appendix. Some issues remain, however, e.g., to standardize a method for S-phase calculation and tetraploid definition.
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| 2. |
- Brown, A. G. A., et al.
(author)
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Gaia Data Release 1 Summary of the astrometric, photometric, and survey properties
- 2016
-
In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 595
-
Journal article (peer-reviewed)abstract
- Context. At about 1000 days after the launch of Gaia we present the first Gaia data release, Gaia DR1, consisting of astrometry and photometry for over 1 billion sources brighter than magnitude 20.7. Aims. A summary of Gaia DR1 is presented along with illustrations of the scientific quality of the data, followed by a discussion of the limitations due to the preliminary nature of this release. Methods. The raw data collected by Gaia during the first 14 months of the mission have been processed by the Gaia Data Processing and Analysis Consortium (DPAC) and turned into an astrometric and photometric catalogue. Results. Gaia DR1 consists of three components: a primary astrometric data set which contains the positions, parallaxes, and mean proper motions for about 2 million of the brightest stars in common with the HIPPARCOS and Tycho-2 catalogues - a realisation of the Tycho-Gaia Astrometric Solution (TGAS) - and a secondary astrometric data set containing the positions for an additional 1.1 billion sources. The second component is the photometric data set, consisting of mean G-band magnitudes for all sources. The G-band light curves and the characteristics of similar to 3000 Cepheid and RR Lyrae stars, observed at high cadence around the south ecliptic pole, form the third component. For the primary astrometric data set the typical uncertainty is about 0.3 mas for the positions and parallaxes, and about 1 mas yr(-1) for the proper motions. A systematic component of similar to 0.3 mas should be added to the parallax uncertainties. For the subset of similar to 94 000 HIPPARCOS stars in the primary data set, the proper motions are much more precise at about 0.06 mas yr(-1). For the secondary astrometric data set, the typical uncertainty of the positions is similar to 10 mas. The median uncertainties on the mean G-band magnitudes range from the mmag level to similar to 0.03 mag over the magnitude range 5 to 20.7. Conclusions. Gaia DR1 is an important milestone ahead of the next Gaia data release, which will feature five-parameter astrometry for all sources. Extensive validation shows that Gaia DR1 represents a major advance in the mapping of the heavens and the availability of basic stellar data that underpin observational astrophysics. Nevertheless, the very preliminary nature of this first Gaia data release does lead to a number of important limitations to the data quality which should be carefully considered before drawing conclusions from the data.
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| 3. |
- Clementini, G., et al.
(author)
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Testing parallaxes with local Cepheids and RR Lyrae stars
- 2017
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 605
-
Journal article (peer-reviewed)abstract
- Context. Parallaxes for 331 classical Cepheids, 31 Type II Cepheids, and 364 RR Lyrae stars in common between Gaia and the HIPPARCOS and Tycho-2 catalogues are published in Gaia Data Release 1 (DR1) as part of the Tycho-Gaia Astrometric Solution (TGAS). Aims. In order to test these first parallax measurements of the primary standard candles of the cosmological distance ladder, which involve astrometry collected by Gaia during the initial 14 months of science operation, we compared them with literature estimates and derived new period-luminosity (PL), period-Wesenheit (PW) relations for classical and Type II Cepheids and infrared PL, PL-metallicity (PLZ), and optical luminosity-metallicity (MV-[Fe/H]) relations for the RR Lyrae stars, with zero points based on TGAS.Methods. Classical Cepheids were carefully selected in order to discard known or suspected binary systems. The final sample comprises 102 fundamental mode pulsators with periods ranging from 1.68 to 51.66 days (of which 33 with sigma(omega)/omega < 0 : 5). The Type II Cepheids include a total of 26 W Virginis and BL Herculis stars spanning the period range from 1.16 to 30.00 days (of which only 7 with sigma(omega)/omega 0 : 5). The RR Lyrae stars include 200 sources with pulsation period ranging from 0.27 to 0.80 days (of which 112 with sigma(omega)/omega < 0 : 5). The new relations were computed using multi- band (V; I; J; K-s) photometry and spectroscopic metal abundances available in the literature, and by applying three alternative approaches: (i) linear least-squares fitting of the absolute magnitudes inferred from direct transformation of the TGAS parallaxes; (ii) adopting astrometry-based luminosities; and (iii) using a Bayesian fitting approach. The last two methods work in parallax space where parallaxes are used directly, thus maintaining symmetrical errors and allowing negative parallaxes to be used. The TGAS-based PL; PW; PLZ, and MV [Fe/H] relations are discussed by comparing the distance to the Large Magellanic Cloud provided by different types of pulsating stars and alternative fitting methods.Results. Good agreement is found from direct comparison of the parallaxes of RR Lyrae stars for which both TGAS and HST measurements are available. Similarly, very good agreement is found between the TGAS values and the parallaxes inferred from the absolute magnitudes of Cepheids and RR Lyrae stars analysed with the Baade-Wesselink method. TGAS values also compare favourably with the parallaxes inferred by theoretical model fitting of the multi-band light curves for two of the three classical Cepheids and one RR Lyrae star, which were analysed with this technique in our samples. The K-band PL relations show the significant improvement of the TGAS parallaxes for Cepheids and RR Lyrae stars with respect to the HIPPARCOS measurements. This is particularly true for the RR Lyrae stars for which improvement in quality and statistics is impressive.Conclusions. TGAS parallaxes bring a significant added value to the previous HIPPARCOS estimates. The relations presented in this paper represent the first Gaia-calibrated relations and form a work-in-progress milestone report in the wait for Gaia-only parallaxes of which a first solution will become available with Gaia Data Release 2 (DR2) in 2018.
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| 4. |
- Danielsson, Anna, 1973, et al.
(author)
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The biological effect of pentoxifylline on the survival of human head and neck cancer cells treated with continuous low and high dose-rate irradiation
- 2005
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In: J Cancer Res Clin Oncol. ; 131:7, s. 459-67
-
Journal article (peer-reviewed)abstract
- AIM: The aim of this study was to compare the radiosensitivity effect of the G2/M arrest-abrogating substance, pentoxifylline (PTX), with high dose-rate irradiation (HDRI) and low dose-rate irradiation (LDRI), during which DNA repair and cell proliferation occur. METHODS: Three squamous cell carcinoma cell lines, FaDu, RPMI 2650 and SCC-61, with differences in genomic imbalance and intrinsic radiosensitivity, were irradiated with 140 cGy/min (HDRI) and 0.7 cGy/min (LDRI) in the presence and absence of 2.0 mM PTX. The surviving fraction at 2.0 Gy (SF2) and cell-cycle phase distribution were assessed by DNA flow cytometry analysis and bromodeoxyuridine incorporation. RESULTS: With HDRI and LDRI the SF2 of FaDu cells decreased by 38.5% and 27.6%, respectively, while the corresponding figures for RPMI 2650 were 28.5% and 48.5%, and for SCC-61 were 44.2% and 28.6%. Increases in G2 populations were evident after both HDRI and LDRI of all cell lines. CONCLUSIONS: The enhancement in the cytotoxic effect of PTX was statistically significant after HDRI as well as after LDRI in all three cell lines. We therefore conclude that PTX in combination with LDRI is worth further study, both in vitro, for disclosing underlying mechanisms, and in vivo, to confirm the findings.
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| 5. |
- Gritli Linde, Amel, 1959, et al.
(author)
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Effects of suramin on polyamine metabolism in B16 murine melanoma cells
- 1998
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In: Anticancer Res. - 0250-7005. ; 18:2A, s. 855-62
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Journal article (peer-reviewed)abstract
- Polyamines and their biosynthetic enzymes, such as ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (AdoMetDC), are crucial for normal and neoplastic cell growth and differentiation. Suramin inhibits the growth of several tumor cells by affecting various intracellular targets, but its effects on polyamines are not known. In this study, the effects of suramin on some parameters of polyamine metabolism in B16 melanoma cells were investigated in vitro. Suramin increased cellular ODC activity and ODC mRNA levels, whereas the drug was directly inhibitory to the enzyme. AdoMetDC was not affected. Cellular putrescine levels were enhanced by suramin, whereas spermidine and spermine pools were unaltered. Cells cultured in the presence of suramin showed decreased cellular polyamine transport, but no direct inhibitory effect on the polyamine transporter could be found. Fluorescence spectroscopy demonstrated a direct interaction between suramin and spermine. It may be concluded that suramin affects polyamine metabolism, and that its effects in some respects are opposite to those of alpha-difluoromethylomithine (DFMO), a specific inhibitor of ODC.
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| 6. |
- Gritli Linde, Amel, 1959, et al.
(author)
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Opposing effects of suramin and DL-alpha-difluoromethylornithine on polyamine metabolism contribute to a synergistic action on B16 melanoma cell growth in vitro
- 1998
-
In: Anticancer Res. - 0250-7005. ; 18:2A, s. 863-70
-
Journal article (peer-reviewed)abstract
- Polyamines are crucial for normal and neoplastic cell growth. Treatment with the polyanionic drug suramin has pronounced antigrowth activity in several tumor cell lines, but its clinical use has been hampered by its toxicity. We have earlier shown that suramin affects cellular polyamine metabolism and transport, and that these effects were, in some respects, opposite to those of alpha-difluoromethylomithine (DFMO), a specific inhibitor to ornithine decarboxylase, a key metabolic enzyme for polyamines. DFMO has been used in anticancer trials, although with limited success. Combinations of suramin and DFMO were, hence, evaluated in vitro and were found to strongly inhibit B16 melanoma cell proliferation. DFMO alone induced melanoma cell differentiation, and suramin used in combination with DFMO did not abrogate this DFMO-induced differentiation. Synergy analysis demonstrated a pronounced growth-inhibitory synergism between suramin and DFMO. The results suggest that the efficacy of combinations of DFMO with suramin or its analogues should be further explored, especially in cells requiring high levels of polyamines for their growth.
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| 7. |
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| 8. |
- Karlsson, Elin, 1979, et al.
(author)
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Chromosomal changes associated with clinical outcome in lymph node-negative breast cancer.
- 2007
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In: Cancer genetics and cytogenetics. - : Elsevier BV. - 0165-4608 .- 1873-4456. ; 172:2, s. 139-46
-
Journal article (peer-reviewed)abstract
- Breast cancer is the most common malignancy among women and accounts for over one million new cases worldwide per year. Lymph node-negative breast cancer patients are reputed as having a better prognosis than lymph node-positive ones. Around 20% of the lymph node-negative patients die within 10 years after diagnosis. To improve the prognostics of node-negative breast cancer, it is important to understand the underlying biologic mechanisms promoting survival, such as specific genetic changes in the tumor genome. In this study, CGH was applied to analyze 64 tumors from node-negative breast cancer patients to identify DNA copy number changes in chromosomes and chromosome regions that may be correlated to survival. The main findings show gains at 4q, 5q31 approximately qter, 6q12 approximately q16, and 12q14 approximately q22, as well as losses of 17p, 18p, and Xq, which were significantly more recurrent in tumors from deceased patients than in tumors from survivors. The average number of chromosomal changes was higher in the tumors from deceased compared to the survivor tumors. Our findings suggest that tumors with specific chromosomal aberrations at 4q, 5q31 approximately qter, 6q12 approximately q16, 12q14 approximately q22, 17p, 18p, and Xq result in an aggressive form of breast cancer and that these patients are predisposed to succumb to breast cancer.
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| 9. |
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| 10. |
- Köpf, Istvan, et al.
(author)
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Characterization of four melanoma cell lines with electron microscopy, immunocytochemistry, cytogenetics, flow cytometry, and southern analysis.
- 1992
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In: Cancer genetics and cytogenetics. - : Elsevier BV. - 0165-4608. ; 62:2, s. 111-23
-
Journal article (peer-reviewed)abstract
- Four cell lines established from human metastatic malignant melanoma, derived from four patients, were analyzed. Ultrastructurally and immunocytochemically, the cultured tumor cells had retained characteristic features of melanocytes and of the primary malignant melanomas. The genetic stability was investigated by repeated flow-cytometric and cytogenetic analyses over 24 months of continuous cultivation. The DNA indices ranged from 1.7 to 2.1 and were stable during the entire period. The same was true for the karyotypes, which had modal numbers ranging from 50 to 84. The most common types of abnormalities were: isochromosomes i(1q), i(9q), translocations (1;17) and (3;6), and other aberrations (1p+,4p+,5p+,11p+,11q-,11q+). Abnormalities involving chromosome 1 were present in all cell lines, but loss of genetic material from chromosome 1p was demonstrated in only one of four cell lines when tested by the Southern blotting technique using a lambda MS1 probe.
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| 11. |
- Köpf, J, et al.
(author)
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Action of interferon alpha and beta on four human melanoma cell lines in vitro.
- 1996
-
In: Anticancer research. - 0250-7005. ; 16:2, s. 791-798
-
Journal article (peer-reviewed)abstract
- Four human melanoma cell lines with different copy numbers of chromosomes 9 and 21q, as studied by the G-band technique, fluorescent in situ hybridisation (FISH) and Polymerase chain reaction (PCR), were tested for their sensitivity to Interferon-alpha (IFN-alpha) and Interferon-beta (IFN-beta) in relation to dosage of interferon genes (#9) and interferon receptor genes (#21p). The two most sensitive cell lines were those containing the highest numbers of #9 per cell, while the number of #21q copies (receptor genes) seemed to have no influence on the interferon sensitivity.
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| 12. |
- Larsson, D. E., et al.
(author)
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Chromosomal damage in two X-ray irradiated cell lines: influence of cell cycle stage and irradiation temperature
- 2007
-
In: Anticancer Research. - 0250-7005 .- 1791-7530. ; 27:2, s. 749-53
-
Journal article (peer-reviewed)abstract
- The aim of this study was to investigate if irradiation with X-rays in different cell cycle phases resulted in a different response as measured with the micronucleus technique. In addition, the influence of irradiation temperature was investigated. MATERIALS AND METHODS: Cells from a non-transformed human fibroblast cell line, HS2429, and a human breast cancer cell line, MCF-7, were synchronized by thymidine block and irradiated at either 2 degrees C or 37 degrees C in the G1-, S- and G2/M-phases. After cytokinesis-block by cytochalasin B, the frequency of micronuclei was determined. RESULTS: Clear dose-response relationships were found. More micronuclei were detected in fibroblast cells irradiated in G1 and S than in G2/M, while the differences were not as prominent in MCF-7 cells. The irradiation temperature had no significant influence on the formation of micronuclei in either of the cell lines. CONCLUSION: The formation of micronuclei varies with the cell cycle stage at the time of irradiation.
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| 13. |
- Levan, Kristina, et al.
(author)
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Identification of a Gene Expression Signature for Survival Prediction in Type I Endometrial Carcinoma
- 2010
-
In: Gene Expression. - : Cognizant Communication Corporation. - 1052-2166 .- 1555-3884. ; 14:6, s. 361-370
-
Journal article (peer-reviewed)abstract
- Endometrial cancer is the most common malignancy of the female reproductive tract. In many cases the prognosis is favorable, but 22% of affected women die from the disease. We aimed to study potential differences in gene expression between endometrioid adenocarcinomas from survivors (5-year survival) and nonsurvivors. Forty-five patients were included in the investigation, of which 21 were survivors and 24 were nonsurvivors. The tumors were analyzed with genome-wide expression array analysis, represented by 13,526 genes. Distinct differences in gene expression were found between the groups. A t-test established that 218 genes were significantly differentially expressed (p < 0.001) between the two survival groups, and in a cross-validation test 40 of the 45 (89%) tumors were classified correctly. The 218 differentially expressed genes were subjected to hierachical clustering analysis, which yielded two clusters both exhibiting over 80% homogeneity with respect to survival. When the additional constraint of fold change (FC > 2) was added the hierachical clustering yielded similar results. Stage I tumors are expected to have a favorable prognosis. However, in our tumor material there were six nonsurvivors with stage I tumors. Five out of six stage I nonsurvivors clustered in the nonsurvival fraction. Our findings suggest that a subgroup of early stage endometroid adenocarcinomas can be correctly classified as potentially aggressive by using molecular biology in combination with conventional markers, thereby providing a tool for a more accurate classification and risk evaluation of the individual patient.
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| 14. |
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| 15. |
- Lyckesvärd, Madeleine Nordén, et al.
(author)
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Alpha particle induced DNA damage and repair in normal cultured thyrocytes of different proliferation status.
- 2014
-
In: Mutation research. Fundamental and molecular mechanisms of mutagenesis. - : Elsevier BV. - 1879-2871 .- 0027-5107. ; 765, s. 48-56
-
Journal article (peer-reviewed)abstract
- Childhood exposure to ionizing radiation increases the risk of developing thyroid cancer later in life and this is suggested to be due to higher proliferation of the young thyroid. The interest of using high-LET alpha particles from Astatine-211 ((211)At), concentrated in the thyroid by the same mechanism as (131)I [1], in cancer treatment has increased during recent years because of its high efficiency in inducing biological damage and beneficial dose distribution when compared to low-LET radiation. Most knowledge of the DNA damage response in thyroid is from studies using low-LET irradiation and much less is known of high-LET irradiation. In this paper we investigated the DNA damage response and biological consequences to photons from Cobolt-60 ((60)Co) and alpha particles from (211)At in normal primary thyrocytes of different cell cycle status. For both radiation qualities the intensity levels of γH2AX decreased during the first 24h in both cycling and stationary cultures and complete repair was seen in all cultures but cycling cells exposed to (211)At. Compared to stationary cells alpha particles were more harmful for cycling cultures, an effect also seen at the pChk2 levels. Increasing ratios of micronuclei per cell nuclei were seen up to 1Gy (211)At. We found that primary thyrocytes were much more sensitive to alpha particle exposure compared with low-LET photons. Calculations of the relative biological effectiveness yielded higher RBE for cycling cells compared with stationary cultures at a modest level of damage, clearly demonstrating that cell cycle status influences the relative effectiveness of alpha particles.
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| 16. |
- Möllerström, Elin, et al.
(author)
-
High-resolution genomic profiling to predict 10-year overall survival in node-negative breast cancer.
- 2010
-
In: Cancer genetics and cytogenetics. - : Elsevier BV. - 1873-4456 .- 0165-4608. ; 198:2, s. 79-89
-
Journal article (peer-reviewed)abstract
- Women with clinically node-negative breast cancer have a better prognosis than do those with axillary lymph node metastasis. Nonetheless, approximately 20% of node-negative patients die within 15 years of diagnosis, and thus additional prognostic markers are greatly needed. To identify specific copy number alterations (CNAs) that differed in frequency between 10-year survivors and deceased patients with node-negative breast cancer, array comparative genomic hybridization (aCGH) was applied to 41 primary node-negative breast tumors. Fisher's exact test was used to identify significantly different CNAs between 10-year survivors and deceased patients. Losses at 8p21.2 approximately p21.3, 8p23.1 approximately p23.2, Xp21.3, and Xp22.31 approximately p22.33 were significantly more common in tumors from deceased patients, suggesting that these alterations may contribute to tumor aggressiveness. Gains at 1q25.2 approximately q25.3 and 1q31.3 approximately q41 were more prevalent in tumors from survivors; specific gains at these genomic regions may inhibit further tumor progression, resulting in a less aggressive form of node-negative breast cancer. Evaluation of the identified CNAs in an independent external data set verified the prognostic potential of the 1q31.3 approximately q41 region. Although further extensive validation is needed, the prognostic CNAs identified in this work may in time facilitate the clinical assessment of breast cancer.
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| 17. |
- Möllerström, Elin, et al.
(author)
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Up-regulation of cell cycle arrest protein BTG2 correlates with increased overall survival in breast cancer, as detected by immunohistochemistry using tissue microarray.
- 2010
-
In: BMC cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 10:1
-
Journal article (peer-reviewed)abstract
- ABSTRACT: BACKGROUND: Previous studies have shown that the ADIPOR1, ADORA1, BTG2 and CD46 genes differ significantly between long-term survivors of breast cancer and deceased patients, both in levels of gene expression and DNA copy numbers. The aim of this study was to characterize the expression of the corresponding proteins in breast carcinoma and to determine their correlation with clinical outcome. METHODS: Protein expression was evaluated using immunohistochemistry in an independent breast cancer cohort of 144 samples represented on tissue microarrays. Fisher's exact test was used to analyze the differences in protein expression between dead and alive patients. We used Cox-regression multivariate analysis to assess whether the new markers predict the survival status of the patients better than the currently used markers. RESULTS: BTG2 expression was demonstrated in a significantly lower proportion of samples from dead patients compared to alive patients, both in overall expression (P=0.026) and cell membrane specific expression (P=0.013), whereas neither ADIPOR1, ADORA1 nor CD46 showed differential expression in the two survival groups. Furthermore, a multivariate analysis showed that a model containing BTG2 expression in combination with HER2 and Ki67 expression along with patient age performed better than a model containing the currently used prognostic markers (tumour size, nodal status, HER2 expression, hormone receptor status, histological grade, and patient age). Interestingly, BTG2 has previously been described as a tumour suppressor gene involved in cell cycle arrest and p53 signalling. CONCLUSIONS: We conclude that high-level BTG2 protein expression correlates with prolonged survival in patients with breast carcinoma.
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| 18. |
- Palm, Stig, 1964, et al.
(author)
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Cell growth kinetics of the human cell line Colo-205 irradiated with photons and astatine-211 alpha-particles
- 2000
-
In: Anticancer Res. - 0250-7005. ; 20:3A, s. 1807-12
-
Journal article (peer-reviewed)abstract
- Cell growth kinetics following Astatine-211 (211At, alpha-particle emitter) and photon irradiation were studied for the human colorectal cell line Colo-205. A growth assay using 96-well plates was chosen. The growth kinetics could be simulated by assuming certain fractions of cells with various proliferative capacities, i.e. from none up to 5 cell doublings, in addition to the defined survivors with remaining unlimited clonogenic capacity. No significant difference in cell growth characteristics was seen between 211At and photon irradiation. The cell doubling time, as calculated from the increment in optical density, was compared with the results from BrdU experiments in the early phases of growth (Tpot = 18.5 +/- 0.6 h for LDR (low dose rate) photon irradiated and 20.3 +/- 0.8 hours for sham-irradiated cells 40-45 hours post-irradiation) confirming the transient accelerated growth of irradiated cells. No statistically significant difference in growth was found between LDR, MDR (medium dose rate) and HDR (high dose rate) photon irradiation.
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| 19. |
- Palm, Stig, 1964, et al.
(author)
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Effects of the alpha-particle emitter At-211 and low-dose-rate gamma-radiation on the human cell line Colo-205 as studied with a growth assay
- 1998
-
In: Anticancer Res. - 0250-7005. ; 18:3A, s. 1671-6
-
Journal article (peer-reviewed)abstract
- BACKGROUND: The aim of this study was to investigate the biological effect of the alpha-particle-emitting isotope astatine-211 on the human cell line Colo-205 and to compare it with that of low-dose-rate gamma-radiation. MATERIALS AND METHODS: Plastic (PMMA) rotating phantoms were constructed, allowing precise dosimetry on a cellular level for both types of radiation. Growth assays using 96-well plates were used to estimate apparent cell survival for the two types of radiation. From this, the relative biological effect (RBE) could be estimated. RESULTS: Irradiation of the cells with 211At resulted in an RBE of 25.1 +/- 6.7 at 37% survival, and 17.3 +/- 2.5 at 10% survival, when compared with low-dose-rate gamma-irradiation. The absorbed dose at 37% survival, 0.12 Gy, corresponds to 2.2 traversals of alpha-particles through the cell nuclei. For cells irradiated with gamma-radiation (1 and 2 Gy), an apparent cell survival above unity was observed up to 50 hours post-irradiation, indicating a possible radiation hormesis effect. CONCLUSIONS: The RBE of 211At found in this growth-assay study was significantly higher than previously presented values. The difference might be due to the use of low-dose-rate gamma-radiation as reference. The RBE presented here could prove valuable when evaluating 211At-labelled compounds for radiotherapy.
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| 20. |
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| 21. |
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| 22. |
- Palm, Stig, 1964, et al.
(author)
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In vitro effects of free 211At,211At-albumin and 211At-monoclonal antibody compared to external photon irradiation on two human cancer cell lines
- 2000
-
In: Anticancer Res. - 0250-7005. ; 20:2A, s. 1005-12
-
Journal article (peer-reviewed)abstract
- BACKGROUND: The aim of this study was to perform various 211At irradiations of importance for the evaluation of 211At-radioimmunotherapy, and compare the effect with that of low linear energy transfer (LET) radiation. MATERIALS AND METHODS: All irradiations were performed on low-concentration single-cell suspensions. Growth assays using 96-well plates were used to estimate apparent cell survival. Centrifuge tube filters were used to estimate the cell uptake and binding of 211At. RESULTS: A relative biological effect (RBE) of 12 +/- 2 (Colo-205) and 5.3 +/- 0.7 (OVCAR-3) was found from 211At-albumin irradiations. There was a 174 +/- 28 times higher free 211At concentration in the cell fraction than in the surrounding medium. For 211At-MAb, an 8,000-30,000 times higher concentration in the cell fraction was achieved, compared to the medium. Corrected for the uptake, an average of 31 +/- 2 ([211At]-astatine) or 26 +/- 5 ([211At]-MAb) decays per cell were required for 37% survival of Colo-205 cells. An average of 19 +/- 3 decays ([211At]-astatine) were required per OVCAR-3 cell. CONCLUSIONS: Cell uptake and binding of 211At was unexpectedly high, possibly favouring its therapeutic use. The binding is probably to the cell surface. The RBE is 5.3 +/- 0.7 for OVCAR-3 and 12 +/- 2 for Colo-205 cells.
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| 23. |
- Palm, Stig, 1964, et al.
(author)
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Single-cell irradiation from [211At] astatine-labeled C215 monoclonal antibody: improved estimates of radiosensitivity from measurements on cellular uptake and retention
- 2003
-
In: Anticancer Res. - 0250-7005. ; 23:2B, s. 1219-21
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Journal article (peer-reviewed)abstract
- New data on the biological effect of 211At-C215 monoclonal antibody in a slowly rotating, widely dispersed single-cell suspension of the human cancer cell line Colo-205 is presented. Cell growth curves of each experiment were used to calculate an apparent cell survival after irradiation. Uptake measurements provided the data needed to calculate the average number of 211At decays per cell in the cell suspension. The results from each experiment were then fit to a mono-exponential function. From the exponential fit, an average of 35 +/- 2 (SD) astatine-211 decays per cell are required for 37% apparent cell survival (D0).
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| 24. |
- Parris, Toshima Z, 1978, et al.
(author)
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Clinical implications of gene dosage and gene expression patterns in diploid breast carcinoma.
- 2010
-
In: Clinical cancer research : an official journal of the American Association for Cancer Research. - 1078-0432. ; 16:15, s. 3860-74
-
Journal article (peer-reviewed)abstract
- Deregulation of key cellular pathways is fundamental for the survival and expansion of neoplastic cells. In cancer, regulation of gene transcription can be mediated in a variety of ways. The purpose of this study was to assess the impact of gene dosage on gene expression patterns and the effect of other mechanisms on transcriptional levels, and to associate these genomic changes with clinicopathologic parameters.
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| 25. |
- Prusti, T., et al.
(author)
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The Gaia mission
- 2016
-
In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 595
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Journal article (peer-reviewed)abstract
- Gaia is a cornerstone mission in the science programme of the European Space Agency (ESA). The spacecraft construction was approved in 2006, following a study in which the original interferometric concept was changed to a direct-imaging approach. Both the spacecraft and the payload were built by European industry. The involvement of the scientific community focusses on data processing for which the international Gaia Data Processing and Analysis Consortium (DPAC) was selected in 2007. Gaia was launched on 19 December 2013 and arrived at its operating point, the second Lagrange point of the Sun-Earth-Moon system, a few weeks later. The commissioning of the spacecraft and payload was completed on 19 July 2014. The nominal five-year mission started with four weeks of special, ecliptic-pole scanning and subsequently transferred into full-sky scanning mode. We recall the scientific goals of Gaia and give a description of the as-built spacecraft that is currently (mid-2016) being operated to achieve these goals. We pay special attention to the payload module, the performance of which is closely related to the scientific performance of the mission. We provide a summary of the commissioning activities and findings, followed by a description of the routine operational mode. We summarise scientific performance estimates on the basis of in-orbit operations. Several intermediate Gaia data releases are planned and the data can be retrieved from the Gaia Archive, which is available through the Gaia home page.
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| 26. |
- van Leeuwen, F., et al.
(author)
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Gaia Data Release 1 : Open cluster astrometry: Performance, limitations, and future prospects
- 2017
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 601
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Journal article (peer-reviewed)abstract
- Context. The first Gaia Data Release contains the Tycho-Gaia Astrometric Solution (TGAS). This is a subset of about 2 million stars for which, besides the position and photometry, the proper motion and parallax are calculated using Hipparcos and Tycho-2 positions in 1991.25 as prior information. Aims. We investigate the scientific potential and limitations of the TGAS component by means of the astrometric data for open clusters. Methods. Mean cluster parallax and proper motion values are derived taking into account the error correlations within the astrometric solutions for individual stars, an estimate of the internal velocity dispersion in the cluster, and, where relevant, the effects of the depth of the cluster along the line of sight. Internal consistency of the TGAS data is assessed. Results. Values given for standard uncertainties are still inaccurate and may lead to unrealistic unit-weight standard deviations of least squares solutions for cluster parameters. Reconstructed mean cluster parallax and proper motion values are generally in very good agreement with earlier Hipparcos-based determination, although the Gaia mean parallax for the Pleiades is a significant exception. We have no current explanation for that discrepancy. Most clusters are observed to extend to nearly 15 pc from the cluster centre, and it will be up to future Gaia releases to establish whether those potential cluster-member stars are still dynamically bound to the clusters. Conclusions. The Gaia DR1 provides the means to examine open clusters far beyond their more easily visible cores, and can provide membership assessments based on proper motions and parallaxes. A combined HR diagram shows the same features as observed before using the Hipparcos data, with clearly increased luminosities for older A and F dwarfs.
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| 27. |
- Zanni, Giulia, et al.
(author)
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Lithium increases proliferation of hippocampal neural stem/progenitor cells and rescues irradiation-induced cell cycle arrest in vitro.
- 2015
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In: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 6
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Journal article (peer-reviewed)abstract
- Radiotherapy in children causes debilitating cognitive decline, partly linked to impaired neurogenesis. Irradiation targets primarily cancer cells but also endogenous neural stem/progenitor cells (NSPCs) leading to cell death or cell cycle arrest. Here we evaluated the effects of lithium on proliferation, cell cycle and DNA damage after irradiation of young NSPCs in vitro.NSPCs were treated with 1 or 3 mM LiCl and we investigated proliferation capacity (neurosphere volume and bromodeoxyuridine (BrdU) incorporation). Using flow cytometry, we analysed apoptosis (annexin V), cell cycle (propidium iodide) and DNA damage (γH2AX) after irradiation (3.5 Gy) of lithium-treated NSPCs.Lithium increased BrdU incorporation and, dose-dependently, the number of cells in replicative phase as well as neurosphere growth. Irradiation induced cell cycle arrest in G1 and G2/M phases. Treatment with 3 mM LiCl was sufficient to increase NSPCs in S phase, boost neurosphere growth and reduce DNA damage. Lithium did not affect the levels of apoptosis, suggesting that it does not rescue NSPCs committed to apoptosis due to accumulated DNA damage.Lithium is a very promising candidate for protection of the juvenile brain from radiotherapy and for its potential to thereby improve the quality of life for those children who survive their cancer.
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| 28. |
- Åström, Lennart, et al.
(author)
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S-phase fraction related to prognosis in localised prostate cancer. No specific significance of chromosome 7 gain or deletion of 7q31.1.
- 1998
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In: International journal of cancer. Journal international du cancer. - 0020-7136. ; 79:6, s. 553-9
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Journal article (peer-reviewed)abstract
- A flow-cytometric (FCM) and fluorescence in situ hybridization (FISH) study was performed in 153 patients with clinically localised prostate cancer (PC) to evaluate retrospectively the prognostic significance of DNA ploidy, S-phase fraction (SPF) and chromosome 7 copy number. Deletions in 7q31.1 were analysed in a subset of 26 tumours. The mean follow-up time was 6 years (range 4-16 years). Twelve cases of benign prostatic hyperplasia (BPH) were studied as a control. Chromosome 7 enumeration and deletion studies were conducted using the alpha-satellite D7Z1 probe and a cosmid probe specific for the marker D7S522 on 7q31.1. Higher SPF was associated with shorter overall survival and shorter time to local progression and metastasis. Near diploid (DNA index 1.05-1.20) cases had a lower frequency of metastases and lower Gleason scores than aneuploid cases. Increased absolute chromosome 7 copy number (centromere count) was associated with higher Gleason score, higher SPF and shorter local progression-free and prostate cancer survival. Absolute chromosome 7 copy number was concordant with FCM DNA ploidy in the majority (75%) of cases. Relative gain or loss of chromosome 7 (centromere counts compared to ploidy) was infrequent, and no correlation was found with clinical parameters. Deletions in 7q31.1 were infrequent. Our results indicate that in localised PC (i) SPF is a prognostic factor, (ii) absolute chromosome 7 copy number is concordant with the ploidy status of the tumour (relative gain or loss of chromosome 7 is infrequent and has no independent prognostic value) and (iii) the frequency of deletions in 7q31.1 is low and not correlated with clinical outcome.
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| 29. |
- Österberg, Lovisa, 1978, et al.
(author)
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Potential predictive markers of chemotherapy resistance in stage III ovarian serous carcinomas.
- 2009
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In: BMC cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 9
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Journal article (peer-reviewed)abstract
- Chemotherapy resistance remains a major obstacle in the treatment of women with ovarian cancer. Establishing predictive markers of chemoresponse would help to individualize therapy and improve survival of ovarian cancer patients. Chemotherapy resistance in ovarian cancer has been studied thoroughly and several non-overlapping single genes, gene profiles and copy number alterations have been suggested as potential markers. The objective of this study was to explore genetic alterations behind chemotherapy resistance in ovarian cancer with the ultimate aim to find potential predictive markers.
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| 30. |
- Österberg, Lovisa, et al.
(author)
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Potential predictive markers of chemotherapy resistance ovarian serous carcinomas
- 2009
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In: BMC Cancer. - : BioMed Central. - 1471-2407. ; 9, s. 368-
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Journal article (peer-reviewed)abstract
- Background Chemotherapy resistance remains a major obstacle in the treatment of women with ovarian cancer. Establishing predictive markers of chemoresponse would help to individualize therapy and improve survival of ovarian cancer patients. Chemotherapy resistance in ovarian cancer has been studied thoroughly and several non-overlapping single genes, gene profiles and copy number alterations have been suggested as potential markers. The objective of this study was to explore genetic alterations behind chemotherapy resistance in ovarian cancer with the ultimate aim to find potential predictive markers.Methods To create the best opportunities for identifying genetic alterations of importance for resistance, we selected a homogenous tumor material concerning histology, stage and chemotherapy. Using high-resolution whole genome array comparative genomic hybridization (CGH), we analyzed the tumor genomes of 40 fresh-frozen stage III ovarian serous carcinomas, all uniformly treated with combination therapy paclitaxel/carboplatin. Fisher's exact test was used to identify significant differences. Subsequently, we examined four genes in the significant regions (EVI1, MDS1, SH3GL2, SH3KBP1) plus the ABCB1 gene with quantitative real-time polymerase chain reaction (QPCR) to evaluate the impact of DNA alterations on the transcriptional level.Results We identified gain in 3q26.2, and losses in 6q11.2-12, 9p22.3, 9p22.2-22.1, 9p22.1-21.3, Xp22.2-22.12, Xp22.11-11.3, and Xp11.23-11.1 to be significantly associated with chemotherapy resistance. In the gene expression analysis, EVI1 expression differed between samples with gain versus without gain, exhibiting higher expression in the gain group.Conclusion In conclusion, we detected specific genetic alterations associated with resistance, of which some might be potential predictive markers of chemotherapy resistance in advanced ovarian serous carcinomas. Thus, further studies are required to validate these findings in an independent ovarian tumor series.
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| 31. |
- Österberg, Lovisa, 1978, et al.
(author)
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Specific Copy Number Alterations Associated with Docetaxel/Carboplatin Response in Ovarian Carcinomas
- 2010
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In: Anticancer Research. - : Highwire Press. - 0250-7005 .- 1791-7530. ; 30:11, s. 4451-4458
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Journal article (peer-reviewed)abstract
- Background: The continued high recurrence and mortality rate in ovarian cancer is a significant problem and the major obstacle in the treatment of ovarian cancer patients is chemotherapy resistance. Thus, finding predictive markers of chemoresistance and elucidating resistance mechanisms is crucial for individualising treatment and improving survival of ovarian cancer patients. Materials and Methods: Using array comparative genomic hybridisation (CGH), this pilot study analysed the tumour genomes of patients treated with docetaxel/carboplatin as first-line chemotherapy (6 resistant versus 24 sensitive cases). This is the first array CGH study of such material. Results: The study identified genetic alterations specific to chemoresistant (gains in 9p13.2-13.1, 9q21.2-21.32, 9q21.33, 9q22.2-22.31, 9q22.32-22.33 and 9q33.1-34.11) and chemosensitive (losses in 8p23.3-23.1 and 8p22) disease. Additionally, when comparing the results to previously analysed tumour material from patients treated with paclitaxel/carboplatin, the two datasets identified different genetic alteration profiles. Conclusion: Specific genetic alterations were identified and associated with chemotherapy response in ovarian cancer. It will be interesting to investigate these exciting data further in larger independent series of ovarian tumours, and hopefully will contribute to the establishment of predictive markers.
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