uu.seUppsala universitets publikasjoner
Endre søk
Begrens søket
12345 1 - 50 of 243
RefereraExporteraLink til resultatlisten
Permanent link
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Treff pr side
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sortering
  • Standard (Relevans)
  • Forfatter A-Ø
  • Forfatter Ø-A
  • Tittel A-Ø
  • Tittel Ø-A
  • Type publikasjon A-Ø
  • Type publikasjon Ø-A
  • Eldste først
  • Nyeste først
  • Skapad (Eldste først)
  • Skapad (Nyeste først)
  • Senast uppdaterad (Eldste først)
  • Senast uppdaterad (Nyeste først)
  • Disputationsdatum (tidligste først)
  • Disputationsdatum (siste først)
  • Standard (Relevans)
  • Forfatter A-Ø
  • Forfatter Ø-A
  • Tittel A-Ø
  • Tittel Ø-A
  • Type publikasjon A-Ø
  • Type publikasjon Ø-A
  • Eldste først
  • Nyeste først
  • Skapad (Eldste først)
  • Skapad (Nyeste først)
  • Senast uppdaterad (Eldste først)
  • Senast uppdaterad (Nyeste først)
  • Disputationsdatum (tidligste først)
  • Disputationsdatum (siste først)
Merk
Maxantalet träffar du kan exportera från sökgränssnittet är 250. Vid större uttag använd dig av utsökningar.
  • 1. Aaltonen, Kirsimari
    et al.
    Amini, Rose-Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Heikkilä, Päivi
    Aittomäki, Kristiina
    Tamminen, A.
    Nevanlinna, Heli
    Blomqvist, Carl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för onkologi.
    High cyclin B1 expression is associated with poor survival in breast cancer2009Inngår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 100, nr 7, s. 1055-60Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Cyclin B1 regulates the G(2)-M transition of the cell cycle. Cyclin B1 expression is higher in premalignant and malignant than normal breast lesions. Correlation of cyclin B1 expression with other histopathological variables and prognostic role in breast cancer are not fully understood. Traditionally used prognostic criteria identify large subset of patients to receive adjuvant chemotherapy and to be exposed to adverse effects. A reliable and simple method helping prognostic evaluation in breast cancer is needed. We analysed cyclin B1 expression on 1348 invasive breast cancers and studied correlations with other histopathological variables and survival. High cyclin B1 correlated with high tumour grade, large tumour size and positive nodal status, oestrogen and progesterone receptor negativity, positive HER2 and p53 status, young age at diagnosis, and high cyclin E, cyclin A and Ki67 expression. Among patients not given adjuvant chemotherapy high cyclin B1 was a strong predictor of shorter overall and metastasis-free survival (RR 3.74, P<0.0005 and RR 3.51, P<0.0005, respectively), and remained as an independent prognostic factor also in multivariate analysis (RR 1.80, P=0.04 and RR 2.31, P=0.02, respectively). This study suggests high cyclin B1 associates with aggressive phenotype and is an independent prognostic factor in breast cancer.

  • 2. Aaltonen, Kirsimari
    et al.
    Amini, Rose-Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Landberg, Göran
    Eerola, Hannaleena
    Aittomäki, Kristiina
    Heikkilä, Päivi
    Nevanlinna, Heli
    Blomqvist, Carl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för onkologi.
    Cyclin D1 expression is associated with poor prognostic features in estrogen receptor positive breast cancer2009Inngår i: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 113, nr 1, s. 75-82Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Cyclins D1 and E play an important role in breast carcinogenesis. High cyclin E expression is common in hormone receptor negative and high grade aggressive breast cancer, whereas cyclin D1 in hormone receptor positive and low grade breast cancer. Experimental data has suggested that cyclin D1 and E mediate cell proliferation by different mechanisms in estrogen receptor (ER) positive and negative breast cancer. To test this hypotheses in large breast cancer material and to clarify the histopathological correlations of cyclin E and D1, especially the association with proliferation, we analyzed cyclin E and D1 immunohistochemical expression on breast tumour microarrays consisting of 1348 invasive breast cancers. High cyclin D1 expression was associated with high grade (P<0.0005), high cyclin A (P<0.0005) and Ki67 (P<0.0005) expression among ER positive but with low grade (P=0.05) and low Ki67 (P=0.01) expression among ER negative breast cancers. Cyclin E and D1 expression correlated positively in ER positive (P<0.0005) but had a negative correlation in ER negative tumours (P=0.004). Cyclin E associated with high grade among all tumours (P<0.0005). In conclusion, the findings of this study show that cyclin D1 has separate roles, and proliferation is driven by different mechanisms in ER positive and negative breast cancers.

  • 3. Aaltonen, Kirsimari
    et al.
    Blomqvist, Carl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för onkologi.
    Amini, Rose-Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Eerola, Hannaleena
    Aittomäki, Kristiina
    Heikkilä, Päivi
    Nevanlinna, Heli
    Familial breast cancers without mutations in BRCA1 or BRCA2 have low cyclin E and high cyclin D1 in contrast to cancers in BRCA mutation carriers2008Inngår i: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 14, nr 7, s. 1976-83Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    PURPOSE: We analyzed the expression of critical cell cycle regulators cyclin E and cyclin D1 in familial breast cancer, focusing on BRCA mutation-negative tumors. Cyclin E expression in tumors of BRCA1 or BRCA2 carriers is higher, and cyclin D1 expression lower, than in sporadic tumors. In familial non-BRCA1/2 tumors, cyclin E and cyclin D1 expression has not been studied. EXPERIMENTAL DESIGN: Cyclin E and cyclin D1 immunohistochemical expression was studied in tissue microarrays consisting of 53 BRCA1, 58 BRCA2, 798 familial non-BRCA1/2, and 439 sporadic breast tumors. RESULTS: In univariate analysis, BRCA1 tumors had significantly more frequently high cyclin E (88%) and low cyclin D1 (84%) expression than sporadic (54% and 49%, respectively) or familial non-BRCA1/2 (38% and 45%, respectively) tumors. BRCA2 tumors had significantly more frequently low cyclin D1 expression (68%) than sporadic or familial non-BRCA1/2 tumors and significantly more frequently high cyclin E expression than familial non-BRCA1/2 tumors. In a logistic regression model, cyclin expression, early age of onset, and estrogen receptor (ER) and human epidermal growth factor receptor-2 (HER2) status were the independent factors most clearly distinguishing tumors of BRCA1 mutation carriers from other familial breast cancers. High cyclin E and low cyclin D1 expression were also independent predictors of BRCA2 mutation when compared with familial non-BRCA1/2 tumors. Most interestingly, lower frequency of high cyclin E expression independently distinguished familial non-BRCA1/2 tumors also from sporadic ones. CONCLUSIONS: Cyclin E and cyclin D1 expression distinguishes non-BRCA1/2 tumors from both sporadic and BRCA1- and BRCA2-associated tumors and may reflect different predisposition and pathogenesis in these groups.

  • 4. Agnarsdóttir, Margrét
    et al.
    Bolander, Åsa
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för onkologi.
    Hedstrand, Håkan
    Strömberg, Sara
    Bergqvist, Michael
    Ponten, Fredrik
    Sooman, Linda
    Hesselius, Patrik
    Ekman, Simon
    Lennartsson, Johan
    Uhlen, Mathias
    Altered Expression of the Transcription Factor SOX10 in Superficial Spreading and Nodular Malignant MelanomasManuskript (Annet vitenskapelig)
  • 5.
    Agnarsdóttir, Margrét
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi, Molekylär och morfologisk patologi.
    Ponten, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi, Molekylär och morfologisk patologi.
    Garmo, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Wagenius, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för onkologi.
    Mucci, Lorelei
    Channing Laboratory, Brigham and Women’s Hospital, Harvard Medical School, Boston, USA, Department of Epidemiology, Harvard School of Public Health, Boston, USA .
    Magnusson, Kristina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi, Molekylär och morfologisk patologi.
    Holmberg, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Eaker-Fält, Sonja
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    MITF as a Prognostic Marker in Cutaneous Malignant MelanomaManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    Background: Microphthalmia associated transcription factor (MITF) protein has a central role in the differentiation and survival of melanocytes. The aim of the study was to investigate whether MITF can be employed as a prognostic marker in patients operated on for cutaneous malignant melanoma.

    Methods: A cohort study design based on information collected from population-based registers. For included patients tissue microarrays and immunohistochemistry were employed to study the protein expression of MITF in the primary malignant melanoma tumors by estimating the fraction of positive tumor cells and the staining intensity.

    Results: The vast majority of tumors expressed MITF in >25% of the tumor cells with a strong staining intensity and looking at these factors individually these patients had a better prognosis. When cell fraction and intensity were combined a high-risk group dying of malignant melanoma was identified as those with 25% -75% of tumor cells staining with weak intensity and those with <25% of tumor cells staining with strong intensity. However, the majority of the deaths occurred in the lower risk groups.

    Conclusions: Although a high-risk group for death in malignant melanoma was identified we conclude that MITF is not useful as a prognostic marker because of the distribution of that particular expression in the population.

    Impact: Our results indicate a bi-phasic pattern of MITF expression and although not useful as a prognostic marker these results are in line with other experimental studies and are relevant to explore further.

     

  • 6.
    Agnarsdóttir, Margrét
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Sooman, Linda
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för onkologi.
    Bolander, Åsa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för onkologi.
    Strömberg, Sara
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Rexhepaj, Elton
    UCD School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin, Ireland.
    Bergqvist, Michael
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för onkologi.
    Pontén, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Gallagher, William
    UCD School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin, Ireland.
    Lennartsson, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Ludwiginstitutet för cancerforskning.
    Ekman, Simon
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för onkologi.
    Uhlen, Mathias
    Department of Proteomics, School of Biotechnology, AlbaNova University Center, KTH-Royal Institute of Technology, Stockholm, Sweden.
    Hedstrand, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Dermatologi och venereologi.
    SOX10 expression in superficial spreading and nodular malignant melanomas2010Inngår i: Melanoma research, ISSN 0960-8931, E-ISSN 1473-5636, Vol. 20, nr 6, s. 468-478Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    SOX10 is a transcription factor expressed in nerve cells and melanocytes. The aim of this study was to investigate the protein expression pattern of SOX10 in malignant melanoma tumors and to analyze whether the results correlated with clinical parameters and the proliferation marker Ki-67. Furthermore, proliferation and migration were analyzed in three different cell lines employing SOX10 small interfering RNA-mediated silencing. Expression patterns were determined in 106 primary tumors and 39 metastases in addition to 16 normal skin samples and six benign nevi employing immunohistochemistry and tissue microarrays. The immunohistochemical staining was evaluated manually and with an automated algorithm. SOX10 was strongly expressed in the benign tissues, but for the malignant tumors superficial spreading melanomas stained stronger than nodular malignant melanomas (P=0.008). The staining intensity was also inversely correlated with T-stage (Spearman's ρ=-0.261, P=0.008). Overall survival and time to recurrence were significantly correlated with SOX10 intensity, but not in multivariate analysis including T-stage. With the automated algorithm there was an inverse correlation between the SOX10 staining intensity and the proliferation marker, Ki-67 (ρ=-0.173, P=0.02) and a significant difference in the intensity signal between the benign tissues, the primary tumors and the metastases where the metastases stained the weakest (P≤0.001). SOX10 downregulation resulted in variable effects on proliferation and migration rates in the melanoma cell lines. In conclusion, the SOX10 intensity level differed depending on the tissue studied and SOX10 might have a role in survival. No conclusion regarding the role of SOX10 for in-vitro proliferation and migration could be drawn.

  • 7. Ahmed, Shahana
    et al.
    Thomas, Gilles
    Ghoussaini, Maya
    Healey, Catherine S.
    Humphreys, Manjeet K.
    Platte, Radka
    Morrison, Jonathan
    Maranian, Melanie
    Pooley, Karen A.
    Luben, Robert
    Eccles, Diana
    Evans, D. Gareth
    Fletcher, Olivia
    Johnson, Nichola
    dos Santos Silva, Isabel
    Peto, Julian
    Stratton, Michael R.
    Rahman, Nazneen
    Jacobs, Kevin
    Prentice, Ross
    Anderson, Garnet L.
    Rajkovic, Aleksandar
    Curb, J. David
    Ziegler, Regina G.
    Berg, Christine D.
    Buys, Saundra S.
    McCarty, Catherine A.
    Feigelson, Heather Spencer
    Calle, Eugenia E.
    Thun, Michael J.
    Diver, W. Ryan
    Bojesen, Stig
    Nordestgaard, Børge G.
    Flyger, Henrik
    Dörk, Thilo
    Schürmann, Peter
    Hillemanns, Peter
    Karstens, Johann H.
    Bogdanova, Natalia V.
    Antonenkova, Natalia N.
    Zalutsky, Iosif V.
    Bermisheva, Marina
    Fedorova, Sardana
    Khusnutdinova, Elza
    Kang, Daehee
    Yoo, Keun-Young
    Noh, Dong Young
    Ahn, Sei-Hyun
    Devilee, Peter
    van Asperen, Christi J.
    Tollenaar, R. A. E. M.
    Seynaeve, Caroline
    Garcia-Closas, Montserrat
    Lissowska, Jolanta
    Brinton, Louise
    Peplonska, Beata
    Nevanlinna, Heli
    Heikkinen, Tuomas
    Aittomäki, Kristiina
    Blomqvist, Carl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för onkologi.
    Hopper, John L.
    Southey, Melissa C.
    Smith, Letitia
    Spurdle, Amanda B.
    Schmidt, Marjanka K.
    Broeks, Annegien
    van Hien, Richard R.
    Cornelissen, Sten
    Milne, Roger L.
    Ribas, Gloria
    González-Neira, Anna
    Benitez, Javier
    Schmutzler, Rita K.
    Burwinkel, Barbara
    Bartram, Claus R.
    Meindl, Alfons
    Brauch, Hiltrud
    Justenhoven, Christina
    Hamann, Ute
    Chang-Claude, Jenny
    Hein, Rebecca
    Wang-Gohrke, Shan
    Lindblom, Annika
    Margolin, Sara
    Mannermaa, Arto
    Kosma, Veli-Matti
    Kataja, Vesa
    Olson, Janet E.
    Wang, Xianshu
    Fredericksen, Zachary
    Giles, Graham G.
    Severi, Gianluca
    Baglietto, Laura
    English, Dallas R.
    Hankinson, Susan E.
    Cox, David G.
    Kraft, Peter
    Vatten, Lars J.
    Hveem, Kristian
    Kumle, Merethe
    Sigurdson, Alice
    Doody, Michele
    Bhatti, Parveen
    Alexander, Bruce H.
    Hooning, Maartje J.
    van den Ouweland, Ans M. W.
    Oldenburg, Rogier A.
    Schutte, Mieke
    Hall, Per
    Czene, Kamila
    Liu, Jianjun
    Li, Yuqing
    Cox, Angela
    Elliott, Graeme
    Brock, Ian
    Reed, Malcolm W. R.
    Shen, Chen-Yang
    Yu, Jyh-Cherng
    Hsu, Giu-Cheng
    Chen, Shou-Tung
    Anton-Culver, Hoda
    Ziogas, Argyrios
    Andrulis, Irene L.
    Knight, Julia A.
    Beesley, Jonathan
    Goode, Ellen L.
    Couch, Fergus
    Chenevix-Trench, Georgia
    Hoover, Robert N.
    Ponder, Bruce A. J.
    Hunter, David J.
    Pharoah, Paul D. P.
    Dunning, Alison M.
    Chanock, Stephen J.
    Easton, Douglas F.
    Newly discovered breast cancer susceptibility loci on 3p24 and 17q23.22009Inngår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 41, nr 5, s. 585-590Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Genome-wide association studies (GWAS) have identified seven breast cancer susceptibility loci, but these explain only a small fraction of the familial risk of the disease. Five of these loci were identified through a two-stage GWAS involving 390 familial cases and 364 controls in the first stage, and 3,990 cases and 3,916 controls in the second stage. To identify additional loci, we tested over 800 promising associations from this GWAS in a further two stages involving 37,012 cases and 40,069 controls from 33 studies in the CGEMS collaboration and Breast Cancer Association Consortium. We found strong evidence for additional susceptibility loci on 3p (rs4973768: per-allele OR = 1.11, 95% CI = 1.08-1.13, P = 4.1 x 10(-23)) and 17q (rs6504950: per-allele OR = 0.95, 95% CI = 0.92-0.97, P = 1.4 x 10(-8)). Potential causative genes include SLC4A7 and NEK10 on 3p and COX11 on 17q.

  • 8. Albertsson, Maria
    et al.
    Johansson, B.
    Friesland, S.
    Kadar, L.
    Letocha, H.
    Frykholm, G.
    Wagenius, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för onkologi.
    Phase II studies on docetaxel alone every third week, or weekly in combination with gemcitabine in patients with primary locally advanced, metastatic, or recurrent esophageal cancer2007Inngår i: Medical Oncology, ISSN 1357-0560, E-ISSN 1559-131X, Vol. 24, nr 4, s. 407-412Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: The purpose of these studies was to compare efficacy and toxicity of docetaxel alone with the combination of gemcitabine and docetaxel for treatment of metastatic esophageal carcinoma. PATIENTS AND METHODS: These studies enrolled patients with histopathologically verified squamous cell carcinoma or adenocarcinoma of the esophagus or cardia. Between March 1997 and June 1999, 52 patients were enrolled in the initial Phase II study (Study 1). They were scheduled for treatment with docetaxel 100 mg/m2 every third week as a 1-h infusion. The second Phase II study between September 2000 and March 2003 included 65 patients (Study II). They were given docetaxel 30 mg/m2, administered as a 30-min i.v. infusion weekly for four times, followed by 2 weeks of rest, and gemcitabine starting with a dose of 750 mg/m2 (if well-tolerated 1,000 mg/m2) on days 1 and 15, followed by 3 weeks of rest. A new cycle began on day 36. Patients were premedicated with betamethasone 8 mg p.o. on the evening before, and 8 mg i.v. 30-60 min before the docetaxel infusion. Response was confirmed by computed tomography and assessed at 12 and 24 weeks. Toxicity was assessed according to WHO scales. RESULTS: In study I, 38 out of the 52 enrolled patients were valuable. Two patients experienced complete remission (CR) (5%), 10 patients partial remission (PR) (26%), nine patients stable disease (SD) (24%), and 17 patients showed progressive disease (PD) (45%). Toxicity mainly involved leukopenia, which in some cases required hospitalization and treatment with antibiotics. In Study II, 46 out of the 65 enrolled patients (70%) were assessable. Out of these, three patients (7%) had CR, eight patients (17%) had PR, 10 patients (22%) had SD, and 25 (54%) PD. Overall response was 24% while an additional 22% showed stable disease. Toxicity mainly consisted of leucopenia and pain. CONCLUSION: Docetaxel as a single agent is active in esophageal cancer, both in treatment naive and in previously treated patients with recurrent disease. The overall response rate was 31%, with a good-safety profile. The addition of gemcitabine is well tolerated, but adds no efficacy. Weekly administration of docetaxel may be less effective. It demonstrates moderate efficacy and the doses used provide an acceptable safety profile.

  • 9. Andersen, Niels S.
    et al.
    Pedersen, Lone B.
    Laurell, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för onkologi.
    Elonen, Erkki
    Kolstad, Arne
    Boesen, Anne Marie
    Pedersen, Lars M.
    Lauritzsen, Grete F.
    Ekanger, Roald
    Nilsson-Ehle, Herman
    Nordstrom, Marie
    Freden, Susanne
    Jerkeman, Mats
    Eriksson, Mikael
    Vaart, Jaan
    Malmer, Beatrice
    Geisler, Christian H.
    Pre-Emptive Treatment With Rituximab of Molecular Relapse After Autologous Stem Cell Transplantation in Mantle Cell Lymphoma2009Inngår i: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 27, nr 26, s. 4365-4370Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Purpose Minimal residual disease (MRD) is predictive of clinical progression in mantle-cell lymphoma (MCL). According to the Nordic MCL-2 protocol we prospectively analyzed the efficacy of pre-emptive treatment using rituximab to MCL patients in molecular relapse after autologous stem cell transplantation (ASCT). Patients and Materials MCL patients enrolled onto the study, who had polymerase chain reaction (PCR) detectable molecular markers and underwent ASCT, were followed with serial PCR assessments of MRD in consecutive bone marrow and peripheral blood samples after ASCT. In case of molecular relapse with increasing MRD levels, patients were offered pre-emptive treatment with rituximab 375 mg/m(2) weekly for 4 weeks. Results Of 160 MCL patients enrolled, 145 underwent ASCT, of whom 78 had a molecular marker. Of these, 74 were in complete remission (CR) and four had progressive disease after ASCT. Of the CR patients, 36 underwent a molecular relapse up to 6 years (mean, 18.5 months) after ASCT. Ten patients did not receive pre-emptive treatment mainly due to a simultaneous molecular and clinical relapse, while 26 patients underwent pre-emptive treatment leading to reinduction of molecular remission in 92%. Median molecular and clinical relapse-free survival after pre-emptive treatment were 1.5 and 3.7 years, respectively. Of the 38 patients who remain in molecular remission for now for a median of 3.3 years (range, 0.4 to 6.6 years), 33 are still in clinical CR. Conclusion Molecular relapse may occur many years after ASCT in MCL, and PCR based pre-emptive treatment using rituximab is feasible, reinduce molecular remission, and may prevent clinical relapse.

  • 10. Andersson, Anne
    et al.
    Enblad, Gunilla
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för onkologi.
    Tavelin, B.
    Björkholm, M.
    Linderoth, J.
    Lagerlöf, I.
    Merup, M.
    Sender, M.
    Malmer, B.
    Family history of cancer as a risk factor for second malignancies after Hodgkin's lymphoma2008Inngår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 98, nr 5, s. 1001-1005Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    This study estimated the risk of second primary malignancies after Hodgkin's lymphoma (HL) in relation to family history of cancer, age at diagnosis and latency, among 6946 patients treated for HL in Sweden in 1965-1995 identified through the Swedish Cancer Register (SCR). First-degree relatives (FDRs) to the HL patients and their malignancies were then ascertained together with their malignancies through the Multi-Generation Registry and SCR. The HL patient cohort was stratified on the number of FDRs with cancer, and standardised incidence ratios (SIRs) of developing SM were analysed. In the HL cohort, 781 SM were observed 1 year or longer after HL diagnosis. The risk for developing SM increased with the number of FDRs with cancer, SIRs being 2.26, 3.01, and 3.45 with 0, 1, or >or=2 FDRs with cancer, respectively. Hodgkin's lymphoma long-term survivors treated at a young age with a family history of cancer carry an increased risk for developing SM and may represent a subgroup where standardised screening for the most common cancer sites could be offered in a stringent surveillance programme.

  • 11. Andersson, Anne
    et al.
    Näslund, Ulf
    Tavelin, Björn
    Enblad, Gunilla
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för onkologi.
    Gustavsson, Anita
    Malmer, Beatrice
    Long-term risk of cardiovascular disease in Hodgkin lymphoma survivors: retrospective cohort analyses and a concept for prospective intervention2009Inngår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 124, nr 8, s. 1914-1917Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Previous studies have shown increased cardiovascular mortality as late side effects in Hodgkin lymphoma (HL) patients. This study identifies stratifying risk factors for surveillance and defines concepts for a clinical feasible and noninvasive prospective protocol for intervention of cardiovascular side effects. HL patients diagnosed between 1965 and 1995 (n = 6.946) and their first-degree relatives (FDR) were identified through the Swedish Cancer Registry and the Swedish Multigeneration Registry. For the HL and FDR cohort, in-patient care for cardiovascular disease (CVD) was registered through the Hospital Discharge Registry, Sweden. Standard incidence ratios of developing CVD for the HL cohort were calculated. A markedly increased risk for in-patient care of CVD was observed in HL patients with HL diagnosed at age 40 years or younger and with more than 10 years follow-up. In the HL survivors, a family history of congestive heart failure (CHF) and coronary artery disease (CAD) increased the risk for these diseases. The Swedish Hodgkin Intervention and Prevention study started in 2007. In the pilot feasibility study for prospective intervention (47 patients), about 25% of the cases had side effects and laboratory abnormalities. These patients were referred to a cardiologist or general practitioner. In the prospective cohort, a positive family history for CHF or CAD could be a stratifying risk factor when setting up a surveillance model. The prospective on-going study presents an intervention model that screens and treats for comorbidity factors. This article also presents an overview of the study concept.

  • 12. Bartkova, Jirina
    et al.
    Tommiska, Johanna
    Oplustilova, Lenka
    Aaltonen, Kirsimari
    Tamminen, Anitta
    Heikkinen, Tuomas
    Mistrik, Martin
    Aittomäki, Kristiina
    Blomqvist, Carl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för onkologi.
    Heikkilä, Päivi
    Lukas, Jiri
    Nevanlinna, Heli
    Bartek, Jiri
    Aberrations of the MRE11-RAD50-NBS1 DNA damage sensor complex in human breast cancer: MRE11 as a candidate familial cancer-predisposing gene2008Inngår i: Molecular Oncology, ISSN 1574-7891, Vol. 2, nr 4, s. 296-316Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The MRE11, RAD50, and NBS1 genes encode proteins of the MRE11-RAD50-NBS1 (MRN) complex critical for proper maintenance of genomic integrity and tumour suppression; however, the extent and impact of their cancer-predisposing defects, and potential clinical value remain to be determined. Here, we report that among a large series of approximately 1000 breast carcinomas, around 3%, 7% and 10% tumours showed aberrantly reduced protein expression for RAD50, MRE11 and NBS1, respectively. Such defects were more frequent among the ER/PR/ERBB2 triple-negative and higher-grade tumours, among familial (especially BRCA1/BRCA2-associated) rather than sporadic cases, and the NBS1 defects correlated with shorter patients' survival. The BRCA1-associated and ER/PR/ERBB2 triple-negative tumours also showed high incidence of constitutively active DNA damage signalling (gamma H2AX) and p53 aberrations. Sequencing the RAD50, MRE11 and NBS1 genes of 8 patients from non-BRCA1/2 breast cancer families whose tumours showed concomitant reduction/loss of all three MRN-complex proteins revealed two germline mutations in MRE11: a missense mutation R202G and a truncating mutation R633STOP (R633X). Gene transfer and protein analysis of cell culture models with mutant MRE11 implicated various destabilization patterns among the MRN complex proteins including NBS1, the abundance of which was restored by re-expression of wild-type MRE11. We propose that germline mutations qualify MRE11 as a novel candidate breast cancer susceptibility gene in a subset of non-BRCA1/2 families. Our data have implications for the concept of the DNA damage response as an intrinsic anti-cancer barrier, various components of which become inactivated during cancer progression and also represent the bulk of breast cancer susceptibility genes discovered to date.

  • 13. Baumann, Pia
    et al.
    Nyman, Jan
    Hoyer, Morten
    Gagliardi, Giovanna
    Lax, Ingmar
    Wennberg, Berit
    Drugge, Ninni
    Ekberg, Lars
    Friesland, Signe
    Johansson, Karl-Axel
    Lund, Jo-Smund
    Morhed, Elisabeth
    Nilsson, Kristina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för onkologi.
    Levin, Nina
    Paludan, Merete
    Sederholm, Christer
    Traberg, Anders
    Wittgren, Lena
    Lewensohn, Rolf
    Stereotactic body radiotherapy for medically inoperable patients with stage I non-small cell lung cancer: a first report of toxicity related to COPD/CVD in a non-randomized prospective phase II study2008Inngår i: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 88, nr 3, s. 359-67Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND AND AIMS: In a retrospective study using stereotactic body radiotherapy (SBRT) in medically inoperable patients with stage I NSCLC we previously reported a local control rate of 88% utilizing a median dose of 15Gyx3. This report records the toxicity encountered in a prospective phase II trial, and its relation to coexisting chronic obstructive pulmonary disease (COPD) and cardio vascular disease (CVD). MATERIAL AND METHODS: Sixty patients were entered in the study between August 2003 and September 2005. Fifty-seven patients (T1 65%, T2 35%) with a median age of 75 years (59-87 years) were evaluable. The baseline mean FEV1% was 64% and median Karnofsky index was 80. A total dose of 45Gy was delivered in three fractions at the 67% isodose of the PTV. Clinical, pulmonary and radiological evaluations were made at 6 weeks, 3, 6, 9, 12, 18, and 36 months post-SBRT. Toxicity was graded according to CTC v2.0 and performance status was graded according to the Karnofsky scale. RESULTS: At a median follow-up of 23 months, 2 patients had relapsed locally. No grade 4 or 5 toxicity was reported. Grade 3 toxicity was seen in 12 patients (21%). There was no significant decline of FEV1% during follow-up. Low grade pneumonitis developed to the same extent in the CVD 3/17 (18%) and COPD 7/40 (18%) groups. The incidence of fibrosis was 9/17 (53%) and pleural effusions was 8/17 (47%) in the CVD group compared with 13/40 (33%) and 5/40 (13%) in the COPD group. CONCLUSION: SBRT for stage I NSCLC patients who are medically inoperable because of COPD and CVD results in a favourable local control rate with a low incidence of grade 3 and no grade 4 or 5 toxicity.

  • 14. Bergh, Jonas
    et al.
    Wiklund, Tom
    Erikstein, Björn
    Lidbrink, Elisabet
    Lindman, Henrik
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för onkologi.
    Malmström, Per
    Kellokumpu-Lehtinen, Pirkko
    Bengtsson, Nils-Olof
    Söderlund, Gustaf
    Anker, Gun
    Wist, Erik
    Ottosson, Susanne
    Salminen, Eeva
    Ljungman, Per
    Holte, Harald
    et al.,
    Tailored fluorouracil, epirubicin, and cyclophosphamide compared with marrow-supported high-dose chemotherapy as adjuvant treatment for high- risk breast cancer: a randomised trial2000Inngår i: The Lancet, Vol. 356, nr 9239, s. 1384-1391Artikkel i tidsskrift (Fagfellevurdert)
  • 15. Berglund, Anders
    et al.
    Holmberg, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Tishelman, Carol
    Wagenius, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för onkologi.
    Eaker, Sonja
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Endokrinkirurgi.
    Lambe, Mats
    Social inequalities in non-small cell lung cancer management and survival: a population-based study in central Sweden2010Inngår i: Thorax, ISSN 0040-6376, E-ISSN 1468-3296, Vol. 65, nr 4, s. 327-333Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives To examine possible associations between socioeconomic status, management and survival of patients with non-small cell lung cancer (NSCLC). Methods In a population-based cohort study, information was retrieved from the Regional Lung Cancer Register in central Sweden, the Cause of Death Register and a social database. ORs and HRs were compared to assess associations between educational level and management and survival. Results 3370 eligible patients with an NSCLC diagnosis between 1996 and 2004 were identified. There were no differences in stage at diagnosis between educational groups. A higher diagnostic intensity was observed in patients with high compared with low education. There were also social gradients in time between referral and diagnosis in early stage disease ( median time: low, 32 days; high, 17 days). Social differences in treatment remained following adjustment for prognostic factors ( surgery in early stage disease, high vs low OR 2.84; CI 1.40 to 5.79). Following adjustment for prognostic factors and treatment, the risk of death in early stage disease was lower in women with a high education ( high vs low HR 0.33; CI 0.14 to 0.77). Conclusion The results of this study indicate that socioeconomically disadvantaged groups with NSCLC receive less intensive care. Low education remained an independent predictor of poor survival only in women with early stage disease. The exact underlying mechanisms of these social inequalities are unknown, but differences in access to care, co-morbidity and lifestyle factors may all contribute.

  • 16.
    Berglund, Mattias
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för onkologi.
    Molecular Characterization of Diffuse Large B-cell Lymphoma and Aspects of Transformation2004Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Lymphomas are a heterogeneous group of neoplasias originating from B- or T-lymphocytes. In this thesis, we determined the genetic and immunophenotypic characterization of DLBCL and their prognostic impact. Moreover, genomic alterations associated with the transformation to DLBCL from Hodgkin lymphoma (HL) and follicular lymphoma (FL) were elucidated.

    In order to outline the impact of cytogenetic as well as immunophenotypic prognostic markers in DLBCL, we firstly studied a series of 54 DLBCL tumors using comparative genomic hybridization (CGH) and we identified several frequently occurring chromosomal imbalances. Loss of 22q was more often found in the diagnostic tumors with a more advanced clinical stage, while gain of 18q21 was more commonly identified in relapses. Secondly, we correlated the expression patterns of CD10, bcl-6, IRF-4 and bcl-2 with clinical parameters in a series of 173 de novo DLBCL patients. Patients with a germinal center (GC) phenotype displayed a better survival than the non-GC group. Expression of bcl-6 and CD10 was correlated with a better survival while bcl-2 expression was associated with a poor prognosis.

    In approaching the HL transformation, two novel B-cell lines (U-2932 and U-2940), derived from patients with DLBCL following HL, were characterized. Interestingly, a translocation with materials from 2q and 7q as well as loss of material on 6q was found in both cell lines. For FL transformation, we assessed chromosomal alterations in a panel of 28 DLBCL patients with a previous history of FL. The DLBCL tumors displayed more chromosomal imbalances compared to FL tumors. Loss of 6q16-21 and gain of 7pter-q22 were more commonly found in the DLBCL counterparts, suggesting the chromosomal location of putative genes that may be involved in the transformation process.

  • 17.
    Berglund, Mattias
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för onkologi.
    Enblad, Gunilla
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för onkologi.
    Turesson, Ingela
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för onkologi.
    Edman, V.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för onkologi.
    Thunberg, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för onkologi.
    Folate-metabolizing genes in lymphoma patients from Sweden2009Inngår i: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 70, nr 4, s. 408-410Artikkel i tidsskrift (Fagfellevurdert)
  • 18.
    Berglund, Mattias
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för onkologi.
    Roos, Göran
    Thunberg, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för onkologi.
    Thymidylate synthase polymorphism relevant for survival in patients with diffuse large B-cell lymphoma?2009Inngår i: Leukemia and Lymphoma, ISSN 1042-8194, E-ISSN 1029-2403, Vol. 50, nr 10, s. 1723-1725Artikkel i tidsskrift (Fagfellevurdert)
  • 19.
    Bergqvist, Michael
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för onkologi.
    Radiosensitivity in lung cancer with focus on p532002Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    In Sweden approximately 2800 new lung cancer patients are diagnosed every year. Radiotherapy is used with curative intention in certain groups of patients. The aim of this thesis is to study the basis of differences in radioresistance and the possibility to predict response to radiotherapy.

    In the first study we investigated, using the comet assay, four lung cancer cell lines with different sensitivity towards radiation. A clear dose-response relationship for radiation-induced DNA single strand and double strand breaks were found. All cell lines showed a remarkably efficient repair of both the DNA single strand and double strand breaks one hour after irradiation. However, further studies in one radioresistant and one radiosensitive cell line demonstrated that repair during the first 15 min had the best accordance with radiosensitivity measured as surviving fraction.

    In the second and third study, sequencing studies of the p53 gene were performed on cell lines as well as on tumour material. Cell lines that were expressing a mutation in exon 7 were associated with increased radiosensitivity compared with tumor cell lines with mutations in other exons. In the clinical study, 10 patients were found to be mutated in the p53 gene whereas the other 10 patients were not. No correlation to clinical parameters could be drawn.

    In the fourth study, serum from 67 patients with a confirmed diagnosis of non-small cell lung cancer was investigated for the presence of p53 antibodies. P53 antibodies in sera, taken prior to radiation treatment, were associated with increased survival.

    The summary of this thesis indicates that the p53 gene has an impact on the effect of radiotherapy in lung cancer. The presence of p53 antibodies might be of clinical interest for predicting survival after radiotherapy. Further studies on the importance of the p53 gene on early repair are of interest.

  • 20.
    Bergström, Mats
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Monazzam, Azita
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för onkologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Endokrin tumörbiologi.
    Razifar, Pasha
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Centrum för bildanalys. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Datoriserad bildanalys.
    Ide, Susan
    Josephsson, Raymond
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Långström, Bengt
    Modeling spheroid growth, PET tracer uptake, and treatment effects of the Hsp90 inhibitor NVP-AUY9222008Inngår i: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 49, nr 7, s. 1204-1210Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    For a PET agent to be successful as a biomarker in early clinical trials of new anticancer agents, some conditions need to be fulfilled: the selected tracer should show a response that is related to the antitumoral effects, the quantitative value of this response should be interpretable to the antitumoral action, and the timing of the PET scan should be optimized to action of the drug. These conditions are not necessarily known at the start of a drug-development program and need to be explored. We proposed a translational imaging activity in which experiments in spheroids and later in xenografts are coupled to modeling of growth inhibition and to the related changes in the kinetics of PET tracers and other biomarkers. In addition, we demonstrated how this information can be used for planning clinical trials. Methods: The first part of this concept is illustrated in a spheroid model with BT474 breast cancer cells treated with the heat shock protein 90 (Hsp90) inhibitor NVP-AUY922. The growth-inhibitory effect after a pulse treatment with the drug was measured with digital image analysis to determine effects on volume with high accuracy. The growth-inhibitory effect was described mathematically by a combined E-max and time course model fitted to the data. The model was then used to simulate a once-per-week treatment, in these experiments the uptake of the PET tracers F-18-FDG and 3'-deoxy-3'-F-18-fluorothymidine (F-18-FLT) was determined at different doses and different time points. Results: A drug exposure of 2 h followed by washout of the drug from the culture medium generated growth inhibition that was maximal at the earliest time point of 1 d and decreased exponentially with time during 10-12 d. The uptake of F-18-FDG per viable tumor volume was minimally affected by the treatment, whereas the F-18-FLT uptake decreased in correlation with the growth inhibition. Conclusion: The study suggests a prolonged action of the Hsp90 inhibitor that supports a once-per-week schedule. F-18-FLT is a suitable tracer for the monitoring of effect, and the F-18-FLT PET study might be performed within 3 d after dosing.

  • 21. Bergström, Stefan
    et al.
    Holgersson, Georg
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för onkologi.
    Bergqvist, Jan-Erik
    Bergqvist, Michael
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för onkologi.
    Ekman, Simon
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för onkologi.
    Stenström, Mats
    Dual-headed Coincidence PET vs. Dedicated PET/CT in the Evaluation of Thoracic Malignancies2010Inngår i: In Vivo, ISSN 0258-851X, E-ISSN 1791-7549, Vol. 24, nr 2, s. 235-238Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The aim of this study was to evaluate the usefulness of coincidence PET imaging as compared with dedicated PET/CT in cancer staging. Patients and Methods: Sixteen patients with thoracic malignancies referred to a PET/CT examination accepted to repeat the acquisition with a coincidence PET system. One experienced nuclear medicine physician compiled a report from the PET/CT examinations and the coincidence PET images. The reports were compared and evaluated according to the degree of agreement: no agreement, unsatisfactory, acceptable or satisfying agreement. Results: Satisfying or acceptable agreement between the PET/CT and the coincidence PET examination was found in 14 out of 16 patients (88%). The main issue for the examining physician was to anatomically locate the FDG uptake in the mediastinum in The coincidence PET images. Conclusion: The data from this small study imply that the staging results obtained with coincidence PET are in most cases concordant with those obtained with dedicated PET/CT.

  • 22. Bernhard, J.
    et al.
    Dietrich, D.
    Glimelius, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för onkologi.
    Hess, V.
    Bodoky, G.
    Scheithauer, W.
    Herrmann, R.
    Estimating prognosis and palliation based on tumour marker CA 19-9 and quality of life indicators in patients with advanced pancreatic cancer receiving chemotherapy2010Inngår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 103, nr 9, s. 1318-1324Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: To investigate the prognostic value of quality of life (QOL) relative to tumour marker carbohydrate antigen (CA) 19-9, and the role of CA 19-9 in estimating palliation in patients with advanced pancreatic cancer receiving chemotherapy. METHODS: CA 19-9 serum concentration was measured at baseline and every 3 weeks in a phase III trial (SAKK 44/00-CECOG/PAN.1.3.001). Patients scored QOL indicators at baseline, and before each administration of chemotherapy (weekly or bi-weekly) for 24 weeks or until progression. Prognostic factors were investigated by Cox models, QOL during chemotherapy by mixed-effect models. RESULTS: Patient-rated pain (P<0.02) and tiredness (P<0.03) were independent predictors for survival, although less prognostic than CA 19-9 (P<0.001). Baseline CA 19-9 did not predict QOL during chemotherapy, except for a marginal effect on pain (P<0.05). Mean changes in physical domains across the whole observation period were marginally correlated with the maximum CA 19-9 decrease. Patients in a better health status reported the most improvement in QOL within 20 days before maximum CA 19-9 decrease. They indicated substantially less pain and better physical well-being, already, early on during chemotherapy with a maximum CA 19-9 decrease of >= 50% vs <50%. CONCLUSION: In advanced pancreatic cancer, pain and tiredness are independent prognostic factors for survival, although less prognostic than CA 19-9. Quality of life improves before best CA 19-9 response but the maximum CA 19-9 decrease has no impact on subsequent QOL. To estimate palliation by chemotherapy, patient's perception needs to be taken into account.

  • 23.
    Birgisson, Helgi
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Ghanipour, Arezo
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Smedh, Kennet
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Västerås.
    Påhlman, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Glimelius, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för onkologi.
    The correlation between a family history of colorectal cancer and survival of patients with colorectal cancer2009Inngår i: Familial Cancer, ISSN 1389-9600, E-ISSN 1573-7292, Vol. 8, nr 4, s. 555-561Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The purpose was to analyze survival of patients with colorectal cancer and a positive family history for colorectal cancer in first degree relatives compared with those with no such family history and to determine whether differences in survival could be explained by known clinico-pathological factors. During 2000-2003, 318 consecutive patients with colorectal cancer answered a written questionnaire about their family history for colorectal cancer. During a 6-year follow-up, recurrences and survival were registered. Thirty-one (10%) patients had a first-degree relative with colorectal cancer, moreover two patients fulfilled the criteria of hereditary non-polyposis colorectal cancer and were excluded. Patients with a first-degree relative with colorectal cancer had better survival and lower risk for recurrences compared to those with no relatives with colorectal cancer. In a multivariate analysis including age, gender, stage of disease, tumor differentiation, vascular invasion and family history, patients with first-degree relatives with colorectal cancer had lower risks for death (RR 0.37; 95% CI 0.17-0.78) and death from cancer (RR 0.25; 95% CI 0.08-0.80), compared to those with a no relative with colorectal cancer. The differences were seen in patients with colon cancer but not rectal cancer. Family history for colorectal cancer in a first-degree relative is an individual prognostic factor in patients with colon cancer and could not be explained by known clinico-pathological factors. The value of family history taking in patients with colon cancer is therefore not only to identify families with hereditary colorectal cancer, but also to add information to the prognosis of the patients.

  • 24.
    Birgisson, Helgi
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Nielsen, Hans J.
    Christensen, Ib Jarle
    Glimelius, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för onkologi.
    Brünner, Nils
    Preoperative plasma TIMP-1 is an independent prognostic indicator in patients with primary colorectal cancer: a prospective validation study2010Inngår i: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 46, nr 18, s. 3323-3331Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Previous studies have suggested plasma tissue inhibitor of metalloproteinases-1 (TIMP-1) as a stage independent prognostic marker in colorectal cancer (CRC) patients. The aim was to validate plasma TIMP-1 and serum carcino-embryonic antigen (CEA) levels as prognostic indicators in an independent population-based cohort of patients with CRC. Patients and methods: During 2000-2003, plasma and serum were collected preoperatively from 322 patients treated for primary CRC. TIMP-1 and CEA levels were determined by validated ELISA platforms. Results: High TIMP-1 and CEA levels each associated with poor overall survival (OS); TIMP-1 (hazard ratio (HR) 2.1; 95% confidence interval (CI) 1.6-2.7) and CEA (HR 1.2; 95% CI 1.1-1.3), and disease-free survival (DFS); TIMP-1 (HR 2.0; 95% CI: 1.5-2.6) and CEA (HR 1.2; 95% CI: 1.1-1.4) in univariate analyses. In stratified analyses of stages II and III, TIMP-1 levels associated significantly with OS and DFS in stages II and III, associations were not found for CEA. Multivariate analysis for OS, including TIMP-1 and CEA levels and clinico-pathological baseline variables, revealed significant association of TIMP-1 (HR 1.8; 95% CI 1.3-2.4) but not CEA levels. Conclusions: This independent prospective validation study confirms the significant association between preoperative plasma TIMP-1 levels and survival of CRC patients: TIMP-1 provided stronger prognostic information than CEA. Thus, this study brings plasma TIMP-1 to the next level of evidence for its clinical use as a prognostic marker in CRC patients.

  • 25. Björkholm, Magnus
    et al.
    Hagberg, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för onkologi.
    Holte, H.
    Kvaloy, S.
    Teerenhovi, L.
    Anderson, H.
    Cavallin-Ståhl, E.
    Myhre, J.
    Pertovaara, H.
    Öst, Å.
    Nilsson, B.
    Ösby, E.
    Central nervous system occurrence in elderly patients with aggressive lymphoma and a long-term follow-up2007Inngår i: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 18, nr 6, s. 1085-1089Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Secondary central nervous system (CNS) involvement by aggressive lymphoma is a well-known and dreadful clinical complication. The incidence and risk factors for CNS manifestation were studied in a large cohort of elderly (>60 years) patients with aggressive lymphoma. PATIENTS AND METHODS: In all, 444 previously untreated patients were randomized to receive 3-weekly combination chemotherapy with cyclophosphamide, doxorubicin, vincristine and prednisone or cyclophosphamide, mitoxantrone, vincristine and prednisone (CNOP) (doxorubicin substituted by mitoxantrone) chemotherapy with or without filgrastim. Prophylactic intrathecal methotrexate was given to patients with lymphoma involvement of bone marrow, testis and CNS near sites. RESULTS: In all 29 of 444 (6.5%) developed CNS disease after a median observation time of 115 months. CNS was the only site of progression/relapse in 13 patients while part of a systemic disease manifestation in 16 patients. In univariate risk factor analysis, CNS occurrence was associated with extranodal involvement of testis (P = 0.002), advanced clinical stage (P = 0.005) and increased age-adjusted International Prognostic Index score (aaIPI; P = 0.035). In multivariate analysis, initial involvement of testis remained significant and clinical stage was of borderline significance. The median survival time was 2 months after presentation of CNS disease. CONCLUSION: A significant proportion of elderly patients with advanced aggressive lymphoma will develop CNS disease. CNS occurrence is related to testis involvement, advanced clinical stage and high aaIPI and the prognosis is dismal.

  • 26. Boerma, M
    et al.
    van der Wees, CG
    Vrieling, H
    Svensson, JP
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för onkologi.
    Wondergem, J
    van der Laarse, A
    Mullenders, LH
    van Zeeland, AA
    Microarray analysis of gene expression profiles of cardiac myo-cytes and fibroblasts after mechanical stress, ionising or ultravio-let radiation2005Inngår i: BMC Genomics, Vol. 6, nr 1, s. 6-Artikkel i tidsskrift (Fagfellevurdert)
  • 27.
    Bolander, Åsa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för onkologi.
    Prognostic Factors in Malignant Melanoma2008Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Because of the failure so far to find effective treatment for patients with advanced stages of melanoma, increasing efforts have been made to find prognostic factors identifying patients in the risk zone for development of metastasis.

    This thesis investigates the prognostic powers of a few selected serological and immunohistochemical biomarkers.

    In the first and second study, patients operated on for localized malignant melanoma were investigated regarding the prognostic impact of angiogenic serological markers and circulating levels of S100. We concluded that the S100 assays, especially S100BB, are potential biomarkers in patients with malignant melanoma, correlated to both survival and disease free survival. However, no such conclusion could be drawn from the first study, where we found no correlation to survival and investigated angiogenic markers.

    In the third and fourth study four new potential immunohistochemical biomarkers where investigated in collaboration with the Swedish Human Protein Atlas Program, and those where TRP-1, galectin-1, DLG5 and syntaxin-7.

    We found that TRP-1 correlated inversely with tumor stage and galectin-1 correlated to Ki-67.

    DLG5 showed a significant inverse correlation to Ki67 and the expression of STX7 was inversely correlated to tumor stage, suggesting that decreased expression is associated with more aggressive tumors.

    None of the investigated markers in study III and IV correlated with disease free survival or overall survival.

    In the fifth and last study, we examined the expression of SOX10, a transcription factor, in different melanocytic lesions. Also, a proliferation assay was carried out in a human melanoma cell line. The results reveal the presence of SOX10 in different melanocytic lesions, with a weak inverse correlation to survival and a significant inverse correlation to T-stage. A significant decrease in proliferation rate for SOX10 silenced cells was found and our data also suggests an increased migratory response in SOX10 silenced cells.

    Delarbeid
    1. The Role of Circulating Angiogenic Factors in Patients Operated on for Localized Malignant Melanoma
    Åpne denne publikasjonen i ny fane eller vindu >>The Role of Circulating Angiogenic Factors in Patients Operated on for Localized Malignant Melanoma
    Vise andre…
    2007 (engelsk)Inngår i: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 27, nr 5A, s. 3211-3217Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Malignant melanoma is a disease capable of rapid progression and rapidly developing metastases. Angiogenesis is a key event signalling tumour progression and elevated levels of angiogenic markers may indicate metastatic disease. No previously published work has, so far, examined plasma vascular endothelial growth factor (VEGF) and its receptor, VEGFR-1, in melanoma. This study investigated circulating levels of the angiogenic factors, VEGF-A and -D, their receptors 1-3 and hepatocyte growth factor (HGF)/scatter factor, in patients shortly after primary surgery for localized malignant melanoma. Elevated circulating levels of VEGF and its receptors, and of HGF, were found postoperatively, possibly derived from the reactive stroma adjacent to the tumours. Using univariate analysis, a correlation between levels of VEGFR-1 and relapse was found, but a correlation between the investigated angiogenic factors and survival could not be established. The results of the present study indicate that production of these angiogenic factors may be due to sources other than malignant melanoma cells.

    Emneord
    Malignant melanoma, angiogenesis, survival, relapse, vascular endothelial growth factor, hepatocyte growth factor, hepatocyte scatter factor
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-97931 (URN)000250266600022 ()17970063 (PubMedID)
    Tilgjengelig fra: 2008-12-22 Laget: 2008-12-22 Sist oppdatert: 2017-12-14bibliografisk kontrollert
    2. Serological and immunohistochemical analysis of S100 and derivatives as markers for prognosis of newly operated malignant melanoma patients
    Åpne denne publikasjonen i ny fane eller vindu >>Serological and immunohistochemical analysis of S100 and derivatives as markers for prognosis of newly operated malignant melanoma patients
    Vise andre…
    2008 (engelsk)Inngår i: Melanoma research, ISSN 0960-8931, E-ISSN 1473-5636, Vol. 18, nr 6, s. 412-419Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    The incidence of cutaneous malignant melanoma is rising, and tumour markers are attracting attention as a possible alternative to clinical examination in the follow-up situation. S100 is the preferred marker for malignant melanoma, and correlation between serum S100 and disease relapse and survival has been reported. S100 tests previously used in clinical studies were specified poorly regarding reactivity with S100A1B and S100BB. In this study, a newly designed S100 assay (designed to measure exclusively S100A1B and S100BB) and two newly developed serological assays, S100A1B, and S100BB, were investigated postoperatively in patients undergoing radical surgery for cutaneous malignant melanoma. Additionally, immunohistochemical analysis of S100A4 was performed on the primary malignant melanoma using tissue microarrays. The primary aim of the study was to investigate whether any of these assays, either singly or in combination, can contribute additional information concerning increased risk of relapse and death because of malignant melanoma. In total, 98 patients (54 males, 44 females) with malignant melanoma were included in the study. As a continuous variable, S100BB (P=0.016) was associated statistically with increased risk of relapse; this was not the case for increased values of either S100 (P=0.11) or S100A1B (P=0.92). The Kaplan-Meier overall survival as well as disease specific survival curve for the S100 serum level demonstrated a statistically significant association with better survival if the patient had a S100 level <or=150 ng/l (P<0.001). Survival analyses for S100A1B using a defined cutoff of 50 ng/l showed a statistically significant association concerning overall and disease specific survival (P<0.001). Furthermore, S100BB was associated with overall and disease specific survival using a defined cutoff of 50 ng/l (P<0.001). No statistically significant correlation was found between S100A4 and overall survival (P=0.96) and there was no correlation between elevated levels of S100 and the immunohistochemical staining of S100A4 (P=0.1), nor for serum S100A1B (P=0.1) nor serum S100BB (P=0.17). Circulating S100A1B and S100BB are potential biomarkers in patients with malignant melanoma. S100BB should be considered as the preferred biomarker, showing potential in predicting both relapse and survival, in contrast to both S100 and S100A1B.

    Emneord
    immunohistochemistry, malignant melanoma, prognosis, S100, S100A1B, S100A4, S100BB, serum marker, survival
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-97932 (URN)10.1097/CMR.0b013e328315c690 (DOI)000261420200006 ()19011512 (PubMedID)
    Tilgjengelig fra: 2008-12-22 Laget: 2008-12-22 Sist oppdatert: 2017-12-14bibliografisk kontrollert
    3. The protein expression of TRP-1 and galectin-1 in cutaneous malignant melanomas
    Åpne denne publikasjonen i ny fane eller vindu >>The protein expression of TRP-1 and galectin-1 in cutaneous malignant melanomas
    Vise andre…
    2008 (engelsk)Inngår i: Cancer Genomics & Proteomics, ISSN 1109-6535, E-ISSN 1790-6245, Vol. 5, nr 6, s. 293-300Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    BACKGROUND: Patients with metastazing malignant melanoma have a poor outcome and determination of thickness of the primary tumor remains as the most important prognostic predictor. The aim of this study was to use an antibody-based proteomics strategy to search for new molecular markers associated with melanoma progression. Two proteins, TRP-1 and galectin-1, were identified as proteins with enhanced expression in cells from the melanocytic lineage. PATIENTS AND METHODS: Protein profiling of TRP-1 and galectin-1 together with proliferation marker Ki-67 and melanocyte marker Melan-A was performed in normal tissues from 144 individuals and in 216 different tumors using tissue microarrays and immunohistochemistry. The protein expression pattern was further analyzed in a defined cohort of 157 patients diagnosed with invasive cutaneous malignant melanoma. RESULTS: Both TRP-1 and galectin-1 were highly expressed in normal melanocytes and melanoma. The expression of TRP-1 was inversely correlated with tumor stage (p=0.002, (R=-0.28)). Neither TRP-1 or galectin-1 was associated with overall or disease free survival (p>0.14, p>0.46 respectively). Ki-67 was associated with tumor stage and survival (p<0.001). CONCLUSION: TRP-1 and galectin-1 protein expression patterns were determined in normal and cancer tissues and both proteins were expressed in the majority of the malignant melanomas. There was no correlation between TRP-1 or galectin-1 expression and survival.

    Emneord
    human Protein Atlas Program, malignant melanoma, TRP-1, galectin-1
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-105314 (URN)19287070 (PubMedID)
    Tilgjengelig fra: 2009-06-03 Laget: 2009-06-03 Sist oppdatert: 2017-12-13bibliografisk kontrollert
    4. Selective expression of Discs large homolog 5 and Syntaxin-7 in benign melanocytes and malignant melanoma
    Åpne denne publikasjonen i ny fane eller vindu >>Selective expression of Discs large homolog 5 and Syntaxin-7 in benign melanocytes and malignant melanoma
    Vise andre…
    Inngår i: Journal of Proteome ResearchArtikkel i tidsskrift (Fagfellevurdert) Submitted
    Identifikatorer
    urn:nbn:se:uu:diva-97934 (URN)
    Tilgjengelig fra: 2008-12-22 Laget: 2008-12-22bibliografisk kontrollert
    5. Altered Expression of the Transcription Factor SOX10 in Superficial Spreading and Nodular Malignant Melanomas
    Åpne denne publikasjonen i ny fane eller vindu >>Altered Expression of the Transcription Factor SOX10 in Superficial Spreading and Nodular Malignant Melanomas
    Vise andre…
    Manuskript (Annet vitenskapelig)
    Identifikatorer
    urn:nbn:se:uu:diva-97935 (URN)
    Tilgjengelig fra: 2008-12-22 Laget: 2008-12-22 Sist oppdatert: 2010-01-13bibliografisk kontrollert
  • 28.
    Bolander, Åsa
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för onkologi.
    Agnarsdóttir, Margrét
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Strömberg, Sara
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Pontén, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Hesselius, Patrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för onkologi.
    Uhlen, Mathias
    Bergqvist, Michael
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för onkologi.
    The protein expression of TRP-1 and galectin-1 in cutaneous malignant melanomas2008Inngår i: Cancer Genomics & Proteomics, ISSN 1109-6535, E-ISSN 1790-6245, Vol. 5, nr 6, s. 293-300Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Patients with metastazing malignant melanoma have a poor outcome and determination of thickness of the primary tumor remains as the most important prognostic predictor. The aim of this study was to use an antibody-based proteomics strategy to search for new molecular markers associated with melanoma progression. Two proteins, TRP-1 and galectin-1, were identified as proteins with enhanced expression in cells from the melanocytic lineage. PATIENTS AND METHODS: Protein profiling of TRP-1 and galectin-1 together with proliferation marker Ki-67 and melanocyte marker Melan-A was performed in normal tissues from 144 individuals and in 216 different tumors using tissue microarrays and immunohistochemistry. The protein expression pattern was further analyzed in a defined cohort of 157 patients diagnosed with invasive cutaneous malignant melanoma. RESULTS: Both TRP-1 and galectin-1 were highly expressed in normal melanocytes and melanoma. The expression of TRP-1 was inversely correlated with tumor stage (p=0.002, (R=-0.28)). Neither TRP-1 or galectin-1 was associated with overall or disease free survival (p>0.14, p>0.46 respectively). Ki-67 was associated with tumor stage and survival (p<0.001). CONCLUSION: TRP-1 and galectin-1 protein expression patterns were determined in normal and cancer tissues and both proteins were expressed in the majority of the malignant melanomas. There was no correlation between TRP-1 or galectin-1 expression and survival.

  • 29.
    Bolander, Åsa
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för onkologi.
    Agnarsdóttir, Margrét
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Wagenius, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi.
    Strömberg, Sara
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Pontén, Fredrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Ekman, Simon
    Brattström, Daniel
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Einarsson, Roland
    Ullenhag, Gustav
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi.
    Hesselius, Patrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi.
    Bergqvist, Michael
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi.
    Serological and immunohistochemical analysis of S100 and derivatives as markers for prognosis of newly operated malignant melanoma patients2008Inngår i: Melanoma research, ISSN 0960-8931, E-ISSN 1473-5636, Vol. 18, nr 6, s. 412-419Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The incidence of cutaneous malignant melanoma is rising, and tumour markers are attracting attention as a possible alternative to clinical examination in the follow-up situation. S100 is the preferred marker for malignant melanoma, and correlation between serum S100 and disease relapse and survival has been reported. S100 tests previously used in clinical studies were specified poorly regarding reactivity with S100A1B and S100BB. In this study, a newly designed S100 assay (designed to measure exclusively S100A1B and S100BB) and two newly developed serological assays, S100A1B, and S100BB, were investigated postoperatively in patients undergoing radical surgery for cutaneous malignant melanoma. Additionally, immunohistochemical analysis of S100A4 was performed on the primary malignant melanoma using tissue microarrays. The primary aim of the study was to investigate whether any of these assays, either singly or in combination, can contribute additional information concerning increased risk of relapse and death because of malignant melanoma. In total, 98 patients (54 males, 44 females) with malignant melanoma were included in the study. As a continuous variable, S100BB (P=0.016) was associated statistically with increased risk of relapse; this was not the case for increased values of either S100 (P=0.11) or S100A1B (P=0.92). The Kaplan-Meier overall survival as well as disease specific survival curve for the S100 serum level demonstrated a statistically significant association with better survival if the patient had a S100 level <or=150 ng/l (P<0.001). Survival analyses for S100A1B using a defined cutoff of 50 ng/l showed a statistically significant association concerning overall and disease specific survival (P<0.001). Furthermore, S100BB was associated with overall and disease specific survival using a defined cutoff of 50 ng/l (P<0.001). No statistically significant correlation was found between S100A4 and overall survival (P=0.96) and there was no correlation between elevated levels of S100 and the immunohistochemical staining of S100A4 (P=0.1), nor for serum S100A1B (P=0.1) nor serum S100BB (P=0.17). Circulating S100A1B and S100BB are potential biomarkers in patients with malignant melanoma. S100BB should be considered as the preferred biomarker, showing potential in predicting both relapse and survival, in contrast to both S100 and S100A1B.

  • 30.
    Bolander, Åsa
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för onkologi.
    Wagenius, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Brattström, Daniel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi.
    Ullenhag, Gustav
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi.
    Hesselius, Patrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi.
    Ekman, Simon
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi.
    Bergqvist, Michael
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi.
    The Role of Circulating Angiogenic Factors in Patients Operated on for Localized Malignant Melanoma2007Inngår i: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 27, nr 5A, s. 3211-3217Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Malignant melanoma is a disease capable of rapid progression and rapidly developing metastases. Angiogenesis is a key event signalling tumour progression and elevated levels of angiogenic markers may indicate metastatic disease. No previously published work has, so far, examined plasma vascular endothelial growth factor (VEGF) and its receptor, VEGFR-1, in melanoma. This study investigated circulating levels of the angiogenic factors, VEGF-A and -D, their receptors 1-3 and hepatocyte growth factor (HGF)/scatter factor, in patients shortly after primary surgery for localized malignant melanoma. Elevated circulating levels of VEGF and its receptors, and of HGF, were found postoperatively, possibly derived from the reactive stroma adjacent to the tumours. Using univariate analysis, a correlation between levels of VEGFR-1 and relapse was found, but a correlation between the investigated angiogenic factors and survival could not be established. The results of the present study indicate that production of these angiogenic factors may be due to sources other than malignant melanoma cells.

  • 31. Braendengen, Morten
    et al.
    Tveit, Kjell M.
    Berglund, Åke
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för onkologi.
    Birkemeyer, Elke
    Frykholm, Gunilla
    Påhlman, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Kolorektalkirurgi.
    Wiig, Johan N.
    Byström, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för onkologi.
    Bujko, Krzysztof
    Glimelius, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för onkologi.
    Randomized phase III study comparing preoperative radiotherapy with chemoradiotherapy in nonresectable rectal cancer2008Inngår i: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 26, nr 22, s. 3687-3694Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    PURPOSE: Preoperative chemoradiotherapy is considered standard treatment for locally advanced rectal cancer, although the scientific evidence for the chemotherapy addition is limited. This trial investigated whether chemotherapy as part of a multidisciplinary treatment approach would improve downstaging, survival, and relapse rate. PATIENTS AND METHODS: The randomized study included 207 patients with locally nonresectable T4 primary rectal carcinoma or local recurrence from rectal carcinoma in the period 1996 to 2003. The patients received either chemotherapy (fluorouracil/leucovorin) administered concurrently with radiotherapy (50 Gy) and adjuvant for 16 weeks after surgery (CRT group, n = 98) or radiotherapy alone (50 Gy; RT group, n = 109). RESULTS: The two groups were well balanced according to pretreatment characteristics. An R0 resection was performed in 82 patients (84%) in the CRT group and in 74 patients (68%) in the RT group (P = .009). Pathologic complete response was seen in 16% and 7%, respectively. After an R0 + R1 resection, local recurrence was found in 5% and 7%, and distant metastases in 26% and 39%, respectively. Local control (82% v 67% at 5 years; log-rank P = .03), time to treatment failure (63% v 44%; P = .003), cancer-specific survival (72% v 55%; P = .02), and overall survival (66% v 53%; P = .09) all favored the CRT group. Grade 3 or 4 toxicity, mainly GI, was seen in 28 (29%) of 98 and six (6%) of 109, respectively (P = .001). There was no difference in late toxicity. CONCLUSION: CRT improved local control, time to treatment failure, and cancer-specific survival compared with RT alone in patients with nonresectable rectal cancer. The treatments were well tolerated.

  • 32.
    Brattström, Daniel
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för onkologi.
    Angiogenesis Related Markers In Non-Small Cell Lung Cancer2003Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    This thesis investigated the predictive and the prognostic powers of angiogenesis related markers in both operable and inoperable non-small cell lung cancer (NSCLC) patients.

    In the first and second study, we investigated the serological fractions of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in 2 cohorts of patients with either operable or inoperable NSCLC.

    Regarding operable NSCLC, we demonstrated significant correlations between VEGF and tumour volume and overall survival. Regarding bFGF, significant correlations with recurrent disease and survival were demonstrated. VEGF and bFGF correlated to each other and with platelet counts. In multivariate analysis, bFGF proved to be a significantly independent prognostic factor.

    Regarding inoperable NSCLC, we demonstrated that patients with elevated bFGF levels before any treatment and during chemotherapy had a significantly poorer survival. During chemotherapy, each rise of one unit of bFGF (ng/L) corresponded to a 4 times increased risk of death. Regarding VEGF, elevated levels after radiotherapy corresponded with better survival. All prognostic information demonstrated in this study concerned patients with a, co-sampled, normal platelet count.

    In the third study, three putative markers, HER-2, EGFR and COX-2, suitable for targeted therapies in resected NSCLC were investigated in a panel of 53 tumours and further investigated for a possible correlation with microvessel density. We demonstrated that HER-2 and COX-2 were mainly expressed in adenocarcinomas, whereas EGFR was only expressed in squamous cell carcinomas. COX-2 showed a trend towards a correlation with microvesssel density. The expression profile, HER-2+/EGFR-, was significantly correlated to poorer survival.

    In the fourth study, a predictive model for recurrences consisting of p53, CD34 and CD105, and circulating serum fractions of VEGF and bFGF, was investigated. The two endothelial markers correlated with each other. CD105 expression correlated with p53 expression. No other significant correlations between markers could be demonstrated. A significant correlation between p53 overexpression and recurrent disease was demonstrated. The mutational status could not confirm the immunohistochemical correlation between p53 and recurrences.

    In conclusion, the present thesis demonstrates that the angiogenic factors VEGF and bFGF analysed in sera have both predictive and prognostic information when measured in operable and inoperable NSCLC. Since HER-2 is overexpressed in NSCLC and linked with prognostic information, this marker might be a suitable target for therapy in NSCLC. Furthermore, in patients with operable NSCLC, p53 expression status was linked with recurrent disease and mean MVD.

    Delarbeid
    1. Elevated preoperative serum levels of angiogenic cytokines correlate to larger primary tumours and poorer survival in non-small cell lung cancer patients
    Åpne denne publikasjonen i ny fane eller vindu >>Elevated preoperative serum levels of angiogenic cytokines correlate to larger primary tumours and poorer survival in non-small cell lung cancer patients
    Vise andre…
    2002 Inngår i: Lung cancer, Vol. 37, nr 1, s. 57-63Artikkel i tidsskrift (Fagfellevurdert) Published
    Identifikatorer
    urn:nbn:se:uu:diva-90769 (URN)
    Tilgjengelig fra: 2003-09-12 Laget: 2003-09-12bibliografisk kontrollert
    2. Serum VEGF and bFGF adds prognostic information in patients with normal platelet counts when sampled before, during and after treatment for locally advanced non-small cell lung cancer
    Åpne denne publikasjonen i ny fane eller vindu >>Serum VEGF and bFGF adds prognostic information in patients with normal platelet counts when sampled before, during and after treatment for locally advanced non-small cell lung cancer
    Vise andre…
    2003 (engelsk)Inngår i: Lung Cancer, ISSN 0169-5002, E-ISSN 1872-8332, Vol. 43, nr 1, s. 55-62Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) have both been implicated to have roles in tumour angiogenesis. In the present retrospective study, serum VEGF and bFGF from patients with locally advanced non-small cell lung cancer (NSCLC) were analysed before, during and after treatment. Seventy-three patients and a total of 460 serum samples were analysed for VEGF and 443 serum samples were analysed for bFGF. Pre-treatment bFGF levels in patients with normal platelet counts, were correlated to poorer survival, P-value = 0.047. During chemotherapy, each rise of one unit bFGF corresponded to a hazard ratio of 4.06 (P=0.022). In patients with normal platelet counts, VEGF levels after radiotherapy significantly correlated to good prognosis (P=0.023), during radiotherapy VEGF levels indicated the same correlation (P=0.085). We conclude that serum VEGF and especially bFGF are of clinical interest as prognostic factors, especially in patients presenting with normal platelet counts.

    Emneord
    Adult, Aged, Aged; 80 and over, Analysis of Variance, Carcinoma; Non-Small-Cell Lung/*blood/pathology/therapy, Female, Fibroblast Growth Factor 2/*blood, Humans, Lung Neoplasms/*blood/pathology/therapy, Male, Middle Aged, Neovascularization; Pathologic/blood, Platelet Count, Predictive Value of Tests, Proportional Hazards Models, Research Support; Non-U.S. Gov't, Retrospective Studies, Survival Analysis, Vascular Endothelial Growth Factor A/*blood
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-90770 (URN)10.1016/j.lungcan.2003.07.007 (DOI)14698537 (PubMedID)
    Tilgjengelig fra: 2003-09-12 Laget: 2003-09-12 Sist oppdatert: 2017-12-14bibliografisk kontrollert
    3. HER-2, EGFR, COX-2 expression status correlated to microvessel density and survival in resected non-small cell lung cancers
    Åpne denne publikasjonen i ny fane eller vindu >>HER-2, EGFR, COX-2 expression status correlated to microvessel density and survival in resected non-small cell lung cancers
    Vise andre…
    2004 (engelsk)Inngår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 43, nr 1, s. 80-86Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    The incidence of lung cancer is increasing throughout the world and is the most common cause of cancer-related death. Early detection followed by surgery has a reasonable, curative potential, but 30-50% of patients experience relapses. The immunohistochemical expressions of HER-2, EGFR and COX-2 were investigated in 53 resected non-small cell lung carcinomas and correlated to microvessel density and clinical data. HER-2, EGFR and COX-2 overexpressions were demonstrated in 15%, 30% and 40% of the tumours, respectively. In adenocarcinomas, HER-2 and COX-2 overexpression were more common, whereas in squamous cell carcinomas, EGFR overexpression was more common. COX-2 expression correlated with HER-2 expression (p = 0.002), and demonstrated a trend towards a correlation with microvessel density (p = 0.10). None of the markers alone had any impact on survival. However, HER-2+/EGFR- tumours proved to have a poor prognosis. In conclusion, adjuvant treatment with HER-2 antagonists might be a future treatment option in resected non-small cell lung cancer patients, especially when HER-2 is overexpressed without a concomitant overexpression of EGFR.

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-90771 (URN)15068324 (PubMedID)
    Tilgjengelig fra: 2003-09-12 Laget: 2003-09-12 Sist oppdatert: 2017-12-14bibliografisk kontrollert
    4. Endothelial markers and circulating angiogenic factors and p53 as markers for recurrence in surgically resected non-small cell lung cancer patients
    Åpne denne publikasjonen i ny fane eller vindu >>Endothelial markers and circulating angiogenic factors and p53 as markers for recurrence in surgically resected non-small cell lung cancer patients
    Vise andre…
    Inngår i: NeoplasiaArtikkel i tidsskrift (Fagfellevurdert) Submitted
    Identifikatorer
    urn:nbn:se:uu:diva-90772 (URN)
    Tilgjengelig fra: 2003-09-12 Laget: 2003-09-12bibliografisk kontrollert
  • 33.
    Brattström, Daniel
    et al.
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för onkologi.
    Bergqvist, Michael
    Hesselius, Patrik
    Larsson, Anders
    Lamberg, Kristina
    Wernlund, Johan
    Brodin, Ola
    Wagenius, Gunnar
    Elevated preoperative serum levels of angiogenic cytokines correlate to larger primary tumours and poorer survival in non-small cell lung cancer patients2002Inngår i: Lung cancer, Vol. 37, nr 1, s. 57-63Artikkel i tidsskrift (Fagfellevurdert)
  • 34.
    Brattström, Daniel
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för onkologi.
    Bergqvist, Michael
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för onkologi.
    Hesselius, Patrik
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Wagenius, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för onkologi.
    Brodin, Ola
    Serum VEGF and bFGF adds prognostic information in patients with normal platelet counts when sampled before, during and after treatment for locally advanced non-small cell lung cancer2003Inngår i: Lung Cancer, ISSN 0169-5002, E-ISSN 1872-8332, Vol. 43, nr 1, s. 55-62Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) have both been implicated to have roles in tumour angiogenesis. In the present retrospective study, serum VEGF and bFGF from patients with locally advanced non-small cell lung cancer (NSCLC) were analysed before, during and after treatment. Seventy-three patients and a total of 460 serum samples were analysed for VEGF and 443 serum samples were analysed for bFGF. Pre-treatment bFGF levels in patients with normal platelet counts, were correlated to poorer survival, P-value = 0.047. During chemotherapy, each rise of one unit bFGF corresponded to a hazard ratio of 4.06 (P=0.022). In patients with normal platelet counts, VEGF levels after radiotherapy significantly correlated to good prognosis (P=0.023), during radiotherapy VEGF levels indicated the same correlation (P=0.085). We conclude that serum VEGF and especially bFGF are of clinical interest as prognostic factors, especially in patients presenting with normal platelet counts.

  • 35.
    Brattström, Daniel
    et al.
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för onkologi.
    Bergqvist, Michael
    Wester, Kenneth
    Hesselius, Patrik
    Ren, Zhi-Ping
    Scheibenpflug, Lena
    Wagenius, Gunnar
    Brodin, Ola
    Endothelial markers and circulating angiogenic factors and p53 as markers for recurrence in surgically resected non-small cell lung cancer patientsInngår i: NeoplasiaArtikkel i tidsskrift (Fagfellevurdert)
  • 36.
    Brattström, Daniel
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för onkologi.
    Wester, Kenneth
    Bergqvist, Michael
    Hesselius, Patrik
    Malmström, Per-Uno
    Nordgren, Hans
    Wagenius, Gunnar
    Brodin, Ola
    HER-2, EGFR, COX-2 expression status correlated to microvessel density and survival in resected non-small cell lung cancers2004Inngår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 43, nr 1, s. 80-86Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The incidence of lung cancer is increasing throughout the world and is the most common cause of cancer-related death. Early detection followed by surgery has a reasonable, curative potential, but 30-50% of patients experience relapses. The immunohistochemical expressions of HER-2, EGFR and COX-2 were investigated in 53 resected non-small cell lung carcinomas and correlated to microvessel density and clinical data. HER-2, EGFR and COX-2 overexpressions were demonstrated in 15%, 30% and 40% of the tumours, respectively. In adenocarcinomas, HER-2 and COX-2 overexpression were more common, whereas in squamous cell carcinomas, EGFR overexpression was more common. COX-2 expression correlated with HER-2 expression (p = 0.002), and demonstrated a trend towards a correlation with microvessel density (p = 0.10). None of the markers alone had any impact on survival. However, HER-2+/EGFR- tumours proved to have a poor prognosis. In conclusion, adjuvant treatment with HER-2 antagonists might be a future treatment option in resected non-small cell lung cancer patients, especially when HER-2 is overexpressed without a concomitant overexpression of EGFR.

  • 37. Byström, P.
    et al.
    Glimelius, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för onkologi.
    Reply to FDG-PET: for early prediction of response to the first-line chemotherapy in metastatic colorectal cancer?2009Inngår i: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 20, nr 6, s. 1150-1150Artikkel i tidsskrift (Fagfellevurdert)
  • 38. Byström, Per
    et al.
    Björkegren, Karin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Allmänmedicin och klinisk epidemiologi.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Johansson, Linda
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Berglund, Åke
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för onkologi.
    Serum vitamin B12 and folate status among patients with chemotherapy treatment for advanced colorectal cancer2009Inngår i: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 114, nr 3, s. 160-164Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: There are conflicting results on the role of cobalamin and folate for epidemiology and carcinogenesis in colorectal cancer patients and the need of supplementation for prevention of chemotherapy toxicity. PATIENTS AND METHODS: Serum cobalamin, folate, and homocysteine were analysed before and during the treatment of 93 patients with advanced colorectal cancer (ACRC) with first-line chemotherapy treatment. This cohort was compared with a healthy control group of 224 individuals. RESULTS: Patients with ACRC had similar cobalamin, folate, and homocysteine values as the healthy control group. There were no correlations between serum cobalamin, folate, and homocysteine values and objective response. There were no correlations to anaemia or other severe toxicity for cobalamin and homocysteine. A total of 12 patients had folate deficiency, and 10 of those suffered from severe toxicity (grade 3 or more). All patients had markedly increased folate values after 2 months of treatment. Folate and homocysteine did not predict patient outcome; however, patients with subclinically low cobalamin values (<300 pmol/L) had significant better overall survival and time to progression than patients with normal or high cobalamin values. CONCLUSION: Patients with ACRC seem to have fairly adequate cobalamin and folate status before and during chemotherapy treatment. This study indicates that ACRC patients receiving chemotherapy do not need supplementation with vitamin B12 and folate. A minor portion of the patients had folate deficiency, and most of those patients had severe toxicity. Patients with subclinically low cobalamin values had surprisingly better survival.

  • 39. Canedo, P.
    et al.
    Thorsélius, M.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Thunberg, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för onkologi.
    Sällström, J.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Sundström, Christer
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Rosén, A.
    Söderberg, Ola
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    A follicular dendritic cell line promotes somatic hypermutations in Ramos cells in vitro2009Inngår i: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 69, nr 1, s. 70-71Artikkel i tidsskrift (Fagfellevurdert)
  • 40. Carella, Angelo Michele
    et al.
    Bellei, Monica
    Brice, Pauline
    Gisselbrecht, Christian
    Visani, Giuseppe
    Colombat, Philippe
    Fabbiano, Francesco
    Donelli, Amedea
    Luminari, Stefano
    Feugier, Pierre
    Browett, Peter
    Hagberg, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för onkologi.
    Federico, Massimo
    High-dose therapy and autologous stem cell transplantation versus conventional therapy for patients with advanced Hodgkin's lymphoma responding to front-line therapy: long-term results2009Inngår i: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 94, nr 1, s. 146-148Artikkel i tidsskrift (Fagfellevurdert)
  • 41.
    Carlsson, Björn
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för klinisk immunologi.
    Sadeghi, Arian
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för klinisk immunologi.
    Bengtsson, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för klinisk immunologi.
    Wagenius, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för onkologi.
    Tötterman, Thomas H.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för klinisk immunologi.
    Effector T cell analysis of melanoma tumor-infiltrating lymphocyte cultures using HLA-ABC semimatched melanoma cell lines2008Inngår i: Journal of immunotherapy (1997), ISSN 1524-9557, E-ISSN 1537-4513, Vol. 31, nr 7, s. 633-43Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The generation of T cells with specific reactivity against tumor-associated antigens is prerequisite for adoptive transfer therapy. Melanoma-specific lymphocyte cultures can be established from tumor-infiltrating lymphocytes (TILs) by in vitro culture with high levels of interleukin-2. In this report, we present TIL data originating from 728 attempted cultures from 33 consecutive melanoma biopsy specimens originating from 30 patients. Cultures were analyzed for the presence of interferon gamma (IFNgamma)-producing cells upon stimulation with a panel of HLA-ABC semimatched melanoma cell lines. We sought to find whether such cell lines could be used to analyze TIL reactivity. Cell lines were used as stimulators to circumvent the need for autologous primary tumor cells. Melanoma-reactive cultures were identified by flow cytometry in 25 of the 30 patients. Four hundred forty-four of 728 (60.9%) cultures contained TILs at the end of experiment. Ninety-one of 318 cultures (28.6%) contained IFNgamma-producing cells after stimulation. In HLA-A*0201 patients IFNgamma analysis was complemented with melanoma-specific tetramer staining. All but one HLA-A*0201 patient had MART-1/Melan-A27-35-directed TILs, with frequencies ranging from 0.1% to 90% of CD8 cells. In addition, tetramer analysis also identified TILs directed against gp100, Tyrosinase, and Her2Neu. Tumor material was collected via needle biopsy in 16 cases and surgery in 18 cases. Overall, surgical material generated more cultures positive for T cells. The described methods are efficient in characterizing clinically relevant melanoma-reactive TILs.

  • 42.
    Carlsson, Jörgen
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för biomedicinsk strålningsvetenskap.
    Blomquist, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för onkologi.
    Gedda, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för biomedicinsk strålningsvetenskap.
    Liljegren, Åsa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för biomedicinsk strålningsvetenskap.
    Malmström, Per-Uno
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi.
    Sjöström, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för biomedicinsk strålningsvetenskap.
    Sundin, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för radiologi.
    Westlin, Jan-Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för onkologi.
    Zhao, Qinghai
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för biomedicinsk strålningsvetenskap.
    Tolmachev, Vladimir
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för biomedicinsk strålningsvetenskap.
    Lundqvist, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för biomedicinsk strålningsvetenskap.
    Conjugate chemistry and cellular processing of EGF-dextran1999Inngår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 38, nr 3, s. 313-321Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Conjugates with specific binding to the epidermal growth factor receptor, EGFR, of interest for radionuclide based imaging and therapy were prepared using mouse epidermal growth factor, mEGF, and dextran. In one type of conjugate, mEGF was coupled to dextran by reductive amination in which the free amino group on the mEGF N-terminal reacted with the aldehyde group on the reductive end of dextran. The end-end coupled conjugate could be further activated by the cyanopyridinium agent CDAP, thereby introducing tyrosines to the dextran part. In the other type of conjugate, the cyanylating procedure using CDAP was applied, first to activate dextran and then allowing for the amino terminus of mEGF to randomly attach to the dextran. In the latter case, radionuclide-labelled tyrosines or glycines could be added in the same conjugation step. All types of mEGF-dextran conjugates had EGFR-specific binding since the binding could be displaced by an excess of non-radioactive mEGF. The conjugates were to a large extent internalized in the test cells and the associated radioactivity was retained intracellularly for different times depending on both the type of cells and conjugate applied. Different intracellular 'traffic routes' for the radionuclides are discussed as well as applications for both imaging and therapy.

  • 43.
    Carlsson, Jörgen
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för biomedicinsk strålningsvetenskap.
    Ren, Z. P.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Wester, K.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för biomedicinsk strålningsvetenskap.
    Sundberg, A. L.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för biomedicinsk strålningsvetenskap.
    Heldin, Nils-Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Hesselager, G.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Persson, M.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för biomedicinsk strålningsvetenskap.
    Gedda, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för biomedicinsk strålningsvetenskap.
    Tolmachev, Vladimir
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för biomedicinsk strålningsvetenskap.
    Lundqvist, Hans
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för biomedicinsk strålningsvetenskap.
    Blomquist, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för onkologi.
    Nistér, M.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Planning for intracavitary anti-EGFR radionuclide therapy of gliomas: Literature review and data on EGFR expression2006Inngår i: Journal of Neuro-Oncology, ISSN 0167-594X, E-ISSN 1573-7373, Vol. 77, nr 1, s. 33-45Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Targeting with radionuclide labelled substances that bind specifically to the epidermal growth factor receptor, EGFR, is considered for intracavitary therapy of EGFR-positive glioblastoma multiforme, GBM. Relevant literature is reviewed and examples of EGFR expression in GBM are given. The therapeutical efforts made so far using intracavitary anti-tenascin radionuclide therapy of GBM have given limited effects, probably due to low radiation doses to the migrating glioma cells in the brain. Low radiation doses might be due to limited penetration of the targeting agents or heterogeneity in the expression of the target structure. In this article we focus on the possibilities to target EGFR on the tumour cells instead of an extracellular matrix component. There seems to be a lack of knowledge on the degree of intratumoral variation of EGFR expression in GBM, although the expression seemed rather homogeneous over large areas in most of the examples (n=16) presented from our laboratory. The observed homogeneity was surprising considering the genomic instability and heterogeneity that generally characterises highly malignant tumours. However, overexpression of EGFR is, at least in primary GBMs, one of the steps in the development of malignancy, and tumour cells that lose or downregulate EGFR will probably be outgrown in an expanding tumour cell population. Thus, loss of EGFR expression might not be the critical factor for successful intracavitary radionuclide therapy. Instead, it is likely that the penetration properties of the targeting agents are critical, and detailed studies on this are urgent.

  • 44.
    Carlsson, Lena
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Lindman, Henrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för onkologi.
    Elevated levels of thymidine kinase 1 peptide in serum from patients with breast cancer2009Inngår i: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 114, nr 2, s. 116-120Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVES: Thymidine kinase (TK) has an important role in DNA synthesis and is thus related to cell proliferation and turn-over. Traditionally, TK has been measured by enzymatic activity or radioimmunoassays. These assays are difficult to adapt to random access instruments. The aim of this study was to evaluate a new immunological sandwich assay for detection of TK peptides in serum from breast cancer patients. MATERIAL AND METHODS: Serum samples were collected from patients with breast cancer and stored frozen at -70 degrees C. The samples were collected after surgery, after metastatic tumor recurrence and after chemotherapy due to tumour recurrence. Patients' serum samples were analysed by the TK enzyme-linked immunosorbent assay (ELISA). RESULTS: In receiver operating characteristics (ROC) analyses of TK1 for diagnosis of breast cancer, the area under the curve (AUC) collected four weeks after surgery was 0.56 (95% CI 0.47-0.65), for samples collected postsurgically after tumour recurrence 0.73 (95% CI 0.65-0.80), and after chemotherapy 0.64 (95% CI 0.56-0.72). CONCLUSIONS: This study indicates that the tumour proliferation marker TK has a potential as a serum marker in breast cancer. Further studies are warranted to verify this observation.

  • 45. Carlsson Tedgren, Åsa
    et al.
    Ahnesjö, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för onkologi.
    Optimization of the computational efficiency of a 3D, collapsed cone dose calculation algorithm for brachytherapy2008Inngår i: Medical physics (Lancaster), ISSN 0094-2405, Vol. 35, nr 4, s. 1611-1618Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Brachytherapy dose calculations based on point kernel superposition using the collapsed cone method have been shown to accurately model the influence from finite dimensions of the patient and effects from heterogeneities including those of high atomic numbers. The collapsed cone method is for brachytherapy applications most effectively implemented through a successive-scattering approach, in which the dose from once and higher order of scattered photons is calculated separately and in successive scatter order. The calculation speed achievable is directly proportional to the number of directions used for point kernel discretization and to the number of voxels in the volume. In this work we investigate how to best divide the total number of directions between the two steps of successive-scattering dose calculations. Results show that the largest fraction of the total number of directions should be utilized in calculating the first-scatter dose. Also shown is how the number of directions required for keeping discretization artifacts at acceptably low levels decreases significantly in multiple-source configurations, as a result of the dose gradients being less steep than those around single sources. Investigating the number of kernel directions required to keep artifacts low enough within the high dose region of an implant (i.e., for dose levels above approximately 5%-10% of the mean central target dose) reveals similar figures for brachytherapy as for external beam applications, where collapsed cone superposition is clinically used. Also shown is that approximating point kernels with their isotropic average leads to small dose differences at low and intermediate energies, implying that the collapsed cone calculations can be done in a single operation common to all sources of the implant at these energies. The current findings show that collapsed cone calculations can be achieved for brachytherapy with the same efficiency as for external beams. This, combined with recent results on gains in efficiency through implementing the algorithm on graphical card parallel hardware indicates that dose can be calculated with account for heterogeneities and finite dimensions within a few seconds for large voxel arrays and is therefore of interest for practical application to treatment planning.

  • 46. Carvalho, Ricardo F S
    et al.
    Mahshid, Yilmaz
    Claesson, Hans-Erik
    Glimelius, Ingrid
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för onkologi.
    Fischer, Marie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi.
    Nilsson, Gunnar
    Expression of mast cell tryptases in Hodgkin and Reed-Sternberg (HRS) cells2008Inngår i: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 67, nr 1, s. 53-56Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Tryptase is the most abundant protease in human mast cells, and is often used as a marker for the enumeration of mast cells in tissue. Here we report that tumour cells from Hodgkin lymphoma, the so called Hodgkin and Reed-Sternberg cells, can express tryptase. Hodgkin lymphoma cell lines expressed mRNA for both alpha- and beta-tryptase and also produced the protein, although at much lower concentrations than mast cells. However, the frequency of tryptase positive HRS-cells in situ was very low. This report demonstrates that tumour cells of lymphoid origin can express tryptase in vitro and in situ.

  • 47.
    Cavalli-Björkman, Nina
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för onkologi.
    Ösby, Eva
    Lundin, Jeanette
    Kalin, Mats
    Österborg, Anders
    Gruber, Astrid
    Fatal adenovirus infection during alemtuzumab (anti-CD52 monoclonal antibody) treatment of a patient with fludarabine-refractory B-cell chronic lymphocytic leukemia2002Inngår i: Medical Oncology, ISSN 1357-0560, E-ISSN 1559-131X, Vol. 19, nr 4, s. 277-80Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Alemtuzumab (Campath-1H) is a humanized CD52 monoclonal antibody that targets normal as well as malignant B- and T-lymphocytes. Alemtuzumab has significant antitumor activity in chronic lymphocytic leukemia (B-CLL) but also induces immunosuppression. We describe a case of fatal adenovirus infection in a heavily pretreated patient with fludarabine-refractory B-CLL receiving alemtuzumab therapy, drawing attention to the fact that also viruses other than cytomegalovirus (CMV) and herpes simplex (HSV) need to be considered in B-CLL patients with fever of unknown origin while on alemtuzumab treatment.

  • 48.
    Cederblad, Lena
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för onkologi.
    Johansson, Silvia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för onkologi.
    Enblad, Gunilla
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för onkologi.
    Engström, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    Blomquist, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för onkologi.
    Cancer of the parotid gland; long-term follow-up: A single centre experience on recurrence and survival2009Inngår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 48, nr 4, s. 549-555Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND:

    The aim of the study was to investigate the results of treatment of malignant parotid gland tumours at a single centre during a 56 year period, focusing on tumour control and survival.

    PATIENTS AND METHODS:

    At Uppsala University Hospital, Sweden, 144 patients (73 male and 71 female) with parotid cancer were treated between 1948 and 2004. The mean and median ages were 62 and 65 years, respectively (range 16-89 years). Surgery was the primary treatment in 113 (78%) patients followed by radiotherapy in 81. Postoperative radiotherapy in doses of 64-66 Gy, where the intention was curative and delivered with either split course or not, was administered to a majority of patients after 1970. The split-course mode was practised between 1970 and 1989. The median follow-up time was 8.3 years for patients still alive. There were 57 (40%) relapses, of which 40 were local recurrences with 26 inside the treatment volume.

    RESULTS:

    The overall 5-year survival was 53%. The majority of tumour-related deaths appeared in the first 3-5 years after diagnosis. Age, co-morbidity, the presence of lymph node metastases, adenoid cystic carcinoma and extent of disease were important for outcome; gender, however, was not. We found no difference in the survival between patients following split course therapy versus continuous fractionation. No difference could be seen in the survival of patients treated in the 1970s versus the 1990s.

    CONCLUSIONS:

    Age, nodal engagement, a higher T-stage, adenoid cystic carcinoma histopathology, facial palsy and intercurrent disease worsen the outcome of patients, whereas gender does not. Treatment principles at our hospital have been surgery followed by radiotherapy since the early 1970s even though a split course technique was practised during a part of this period. Survival has not improved markedly. Thus, there is scope for improvement for this group of patients.

  • 49. Ciray, Ipec
    et al.
    Lindman, Henrik
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för onkologi.
    Åström, Gunnar
    Wanders, Alkwin
    Bergh, Jonas
    Ahlström, Håkan
    Effect of Granulocyte Colony-Stimulating Factor (G-CSF)-supported chemotherapy on MR imaging of normal red bone marrow in breast cancer patients with focal bone metastases2003Inngår i: Acta Radiologica, ISSN 0284-1851, Vol. 44, nr 5, s. 472-484Artikkel i tidsskrift (Fagfellevurdert)
  • 50. Cox, Angela
    et al.
    Dunning, Alison M.
    Garcia-Closas, Montserrat
    Balasubramanian, Sabapathy
    Reed, Malcolm W. R.
    Pooley, Karen A.
    Scollen, Serena
    Baynes, Caroline
    Ponder, Bruce A. J.
    Chanock, Stephen
    Lissowska, Jolanta
    Brinton, Louise
    Peplonska, Beata
    Southey, Melissa C.
    Hopper, John L.
    McCredie, Margaret R. E.
    Giles, Graham G.
    Fletcher, Olivia
    Johnson, Nichola
    dos Santos Silva, Isabel
    Gibson, Lorna
    Bojesen, Stig E.
    Nordestgaard, Børge G.
    Axelsson, Christen K.
    Torres, Diana
    Hamann, Ute
    Justenhoven, Christina
    Brauch, Hiltrud
    Chang-Claude, Jenny
    Kropp, Silke
    Risch, Angela
    Wang-Gohrke, Shan
    Schürmann, Peter
    Bogdanova, Natalia
    Dörk, Thilo
    Fagerholm, Rainer
    Aaltonen, Kirsimari
    Blomqvist, Carl
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för onkologi.
    Nevanlinna, Heli
    Seal, Sheila
    Renwick, Anthony
    Stratton, Michael R.
    Rahman, Nazneen
    Sangrajrang, Suleeporn
    Hughes, David
    Odefrey, Fabrice
    Brennan, Paul
    Spurdle, Amanda B.
    Chenevix-Trench, Georgia
    Beesley, Jonathan
    Mannermaa, Arto
    Hartikainen, Jaana
    Kataja, Vesa
    Kosma, Veli-Matti
    Couch, Fergus J.
    Olson, Janet E.
    Goode, Ellen L.
    Broeks, Annegien
    Schmidt, Marjanka K.
    Hogervorst, Frans B. L.
    Van't Veer, Laura J.
    Kang, Daehee
    Yoo, Keun-Young
    Noh, Dong-Young
    Ahn, Sei-Hyun
    Wedrén, Sara
    Hall, Per
    Low, Yen-Ling
    Liu, Jianjun
    Milne, Roger L
    Ribas, Gloria
    Gonzalez-Neira, Anna
    Benitez, Javier
    Sigurdson, Alice J.
    Stredrick, Denise L.
    Alexander, Bruce H.
    Struewing, Jeffery P.
    Pharoah, Paul D. P.
    Easton, Douglas F.
    A common coding variant in CASP8 is associated with breast cancer risk2007Inngår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 39, nr 3, s. 352-358Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The Breast Cancer Association Consortium (BCAC) has been established to conduct combined case-control analyses with augmented statistical power to try to confirm putative genetic associations with breast cancer. We genotyped nine SNPs for which there was some prior evidence of an association with breast cancer: CASP8 D302H (rs1045485), IGFBP3 -202 C --> A (rs2854744), SOD2 V16A (rs1799725), TGFB1 L10P (rs1982073), ATM S49C (rs1800054), ADH1B 3' UTR A --> G (rs1042026), CDKN1A S31R (rs1801270), ICAM5 V301I (rs1056538) and NUMA1 A794G (rs3750913). We included data from 9-15 studies, comprising 11,391-18,290 cases and 14,753-22,670 controls. We found evidence of an association with breast cancer for CASP8 D302H (with odds ratios (OR) of 0.89 (95% confidence interval (c.i.): 0.85-0.94) and 0.74 (95% c.i.: 0.62-0.87) for heterozygotes and rare homozygotes, respectively, compared with common homozygotes; P(trend) = 1.1 x 10(-7)) and weaker evidence for TGFB1 L10P (OR = 1.07 (95% c.i.: 1.02-1.13) and 1.16 (95% c.i.: 1.08-1.25), respectively; P(trend) = 2.8 x 10(-5)). These results demonstrate that common breast cancer susceptibility alleles with small effects on risk can be identified, given sufficiently powerful studies.

12345 1 - 50 of 243
RefereraExporteraLink til resultatlisten
Permanent link
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf