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  • 1.
    Andreasson, Håkan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Wanders, Alkwin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Sun, Xiao-Feng
    Willén, Roger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Graf, Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Nygren, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Zhang, Zhi-Yong
    Mahteme, Haile
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Histopathological Classification of Pseudomyxoma Peritonei and the Prognostic Importance of PINCH Protein2012In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 32, no 4, p. 1443-1448Article in journal (Refereed)
    Abstract [en]

    Aim:

    The aims of this study were i) to assess a new and more detailed histopathological classification and to analyze concordance between pathologists in the histopathological classification of pseudomyxoma peritonei (PMP); ii) to analyze the expression in the stroma of the particularly interesting new cysteine-histidine (PINCH) protein and its prognostic importance in PMP.

    Materials and Methods:

    Surgical specimens from 81 patients, classified according to the Ronnett et al histopathological classification were compared to a new system with four groups ranging from indolent to aggressive growth patterns. PINCH protein expression was analyzed and was related to clinical variables.

    Results:

    The new four-group classification provided better prognostic information than the classification according to Ronnett et al. (p=0.04). Expression of the PINCH protein in the stroma was found in 83% of the cases and was associated with high tumor burden (p=0.002) and a poor prognosis (p=0.04).

    Conclusion:

    The proposed new PMP classification system may provide additional prognostic information. PINCH protein is expressed in PMP and has prognostic information.

  • 2.
    Backlin, Carin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Rastad, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Skogseid, Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Hellman, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Åkerström, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Juhlin, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Immunohistochemical expression of insulin-like growth factor 1 and its receptor in normal and neoplastic human adrenal cortex1995In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 15, no 6B, p. 2453-2459Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Insulin-like growth factor 1 (IGF-1) may influence cellular growth, differentiation and secretion.

    MATERIAL AND METHODS:

    Cryosectioned normal human adrenal glands (n = 6), cortical adenoma (n = 21), and carcinoma (n = 17) were stained immunohistochemically for IGF-1 and its receptor, and human adrenocortical cancer cells expressing the receptor were analysed for influences on proliferation.

    RESULTS:

    Normal cortical parenchyma generally displayed faint IGF-1 reactivity and intracellular receptor staining. Similar labelling encompassed the adenomas, but only 6 of them were receptor reactive. IGF-1 expression was conspicuous in 11 carcinomas, and 6 of them displayed cell surface receptor reactivity. All aldosterone producing lesions were receptor antibody unreactive. Recombinant IGF-1 dose-dependently stimulated the cell proliferation, and this effect was reversed by the receptor antibody.

    CONCLUSION:

    IGF-1 may interact with function and proliferation of the human adrenal cortex with particular reference to cortical carcinomas lacking discernible aldosterone excess.

  • 3.
    Backman, Samuel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Experimental Surgery.
    Norlén, Olov
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Eriksson, Barbro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Skogseid, Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Stålberg, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Crona, Joakim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Detection of Somatic Mutations in Gastroenteropancreatic Neuroendocrine Tumors Using Targeted Deep Sequencing2017In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 37, no 2, p. 705-712Article in journal (Refereed)
    Abstract [en]

    Mutations affecting the mechanistic target of rapamycin (MTOR) signalling pathway are frequent in human cancer and have been identified in up to 15% of pancreatic neuroendocrine tumours (NETs). Grade A evidence supports the efficacy of MTOR inhibition with everolimus in pancreatic NETs. Although a significant proportion of patients experience disease stabilization, only a minority will show objective tumour responses. It has been proposed that genomic mutations resulting in activation of MTOR signalling could be used to predict sensitivity to everolimus.

    PATIENTS AND METHODS: Patients with NETs that underwent treatment with everolimus at our Institution were identified and those with available tumour tissue were selected for further analysis. Targeted next-generation sequencing (NGS) was used to re-sequence 22 genes that were selected on the basis of documented involvement in the MTOR signalling pathway or in the tumourigenesis of gastroenterpancreatic NETs. Radiological responses were documented using Response Evaluation Criteria in Solid Tumours.

    RESULTS: Six patients were identified, one had a partial response and four had stable disease. Sequencing of tumour tissue resulted in a median sequence depth of 667.1 (range=404-1301) with 1-fold coverage of 95.9-96.5% and 10-fold coverage of 87.6-92.2%. A total of 494 genetic variants were discovered, four of which were identified as pathogenic. All pathogenic variants were validated using Sanger sequencing and were found exclusively in menin 1 (MEN1) and death domain associated protein (DAXX) genes. No mutations in the MTOR pathway-related genes were observed.

    CONCLUSION: Targeted NGS is a feasible method with high diagnostic yield for genetic characterization of pancreatic NETs. A potential association between mutations in NETs and response to everolimus should be investigated by future studies.

  • 4.
    Blomberg, Carl
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
    Nilsson, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
    Holgersson, Georg
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science.
    Edlund, Per
    Bergqvist, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
    Adwall, Linda
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Ekman, Simon
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Brattström, Daniel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Bergström, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Randomized Trials of Systemic Medically-treated Malignant Mesothelioma: A Systematic Review2015In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 35, no 5, p. 2493-2501Article, review/survey (Refereed)
    Abstract [en]

    Malignant pleural mesothelioma (MPM) is a rare but aggressive malignancy mainly localized to the pleura. Malignant mesothelioma grows highly invasive into surrounding tissue and has a low tendency to metastasize. The median overall survival (OS) of locally advanced or metastatic disease without treatment is 4-13 months but, during recent years, improvement in survival has been achieved since treatment for patients with mesothelioma has improved with better palliative care, systemic medical treatment, surgery and improved diagnostics methods. The present review aims at describing available data from randomized trials considering systemic medical treatment for this patient category.

  • 5.
    Bolander, Åsa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Wagenius, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Brattström, Daniel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Ullenhag, Gustav
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Hesselius, Patrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Ekman, Simon
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Bergqvist, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    The Role of Circulating Angiogenic Factors in Patients Operated on for Localized Malignant Melanoma2007In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 27, no 5A, p. 3211-3217Article in journal (Refereed)
    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.

  • 6.
    Bäckman, Ulrika
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Svensson, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Christofferson, Rolf H.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Azarbayjani, Faranak
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    The Bisphosphonate Zoledronic Acid Reduces Experimental Neuroblastoma Growth by Interference with Tumor Angiogenesis2008In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 28, no 3A, p. 1551-1557Article in journal (Refereed)
    Abstract [en]

    Background: Zoledronic acid is a new member of the bisphosphonate (BP) class of compounds, a family of closely related synthetic molecules originally derived from the naturally occurring pyrophosphate. These compounds that are potent inhibitors of bone resorption, have been shown to reduce the growth of several cancer cell lines in vitro, and can act as inhibitors of angiogenesis. The angiogenesis inhibitor TNP-470, a synthetic analogue of the fungal antibiotic fumagillin, has been shown to inhibit the growth of multiple tumors in vivo, and is currently in Phase H clinical trials for cancer. Materials and Methods: The effects of daily subcutaneous (s.c.) administration of zoledronic acid (0.1 mg/kg) were compared with those of TNP-470 (15 mg/kg/day and 30 mg/kg every other day, s.c.) in a nude mouse xenograft model for the childhood cancer, neuroblastoma (NB). Results: Zoledronic acid reduced the tumor growth by 33% whereas TNP-470 was less effective and reduced the tumor growth by 26% and 11% for animals treated with 15 mg/kg/day and 30 mg/kg every other day, respectively. Analysis of angiogenesis showed a significant reduction of the number of vessels per grid and in vessel length in all the treatment groups. Conclusion: Zoledronic acid shows tumoristatic and angiostatic properties that might be beneficial in the treatment of solid tumors such as neuroblastoma.

  • 7.
    Carlsson, Jorgen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Biomedical Radiation Sciences.
    Imaging ff HER2-Expression in Breast Cancer Metastases (Review)2014In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 34, no 10, p. 5855-5855Article in journal (Other academic)
  • 8.
    Carlsson, Maria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Strang, Peter
    Bjurström, Christina
    Treatment modality affects long-term quality of life in gynaecological cancer.2000In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 20, no 1B, p. 563-568Article in journal (Refereed)
    Abstract [en]

    In order to survey the side effects after cancer treatment, quality of life data were collected from females in clinical remission.

    MATERIALS AND METHODS

    The study was cross-sectional; every patient that visited the outpatient clinic during a period of three months was asked to anonymously complete the EORTC QLQ-C30 questionnaire and five additional specific questions related to gynaecological cancer.

    RESULTS

    In total, 235 patients (90%) returned the questionnaire. In general, both the levels of functioning and symptomatology were time-dependent. Patients with short treatment-free intervals reported more problems than the others. When using treatment modality as an independent variable in the statistical calculations, a treatment-related effect on functioning and symptomatology was demonstrated (p < 0.05 to p < 0.001). Patients previously treated with chemotherapy had poorer role- and cognitive functioning and more problems with fatigue, nausea, vomiting, dyspnoea, constipation and financial problems, compared with those not treated with chemotherapy (p < 0.05 to p < 0.01). Those patients who had been treated with external radiotherapy and/or brachytherapy had significantly more problems with flatulence and diarrhoea (p < 0.05 to p < 0.001). In conclusion, patients who underwent treatment for gynaecological cancer reported long-term side effects also many years after finishing treatment. The problems where related to treatment modality which should be considered, especially when planning adjuvant treatment.

  • 9. Dasu, Alexandru
    et al.
    Flejmer, Anna M.
    Dohlmar, Frida
    Josefsson, Dan
    Nyström, Petra Witt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    The Potential Benefit of Scanned Proton Beam Versus Intensity Modulated Photon Therapy as Adjuvant Radiation Therapy in Breast Cancer2014In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 34, no 10, p. 5873-5874Article in journal (Other academic)
  • 10. Djureinovic, Tatjana
    et al.
    Lindblom, Annika
    Dalén, Johan
    Dedorson, Stefan
    Edler, David
    Hjern, Fredrik
    Holm, Jörn
    Lenander, Claes
    Lindforss, Ulrik
    Lundqvist, Nils
    Olivecrona, Hans
    Olsson, Louise
    Påhlman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Rutegård, Jörgen
    Smedh, Kennet
    Törnqvist, Anders
    Eiberg, Hans
    Bisgaard, Marie Luise
    The CHEK2 1100delC variant in Swedish colorectal cancer2006In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 26, no 6C, p. 4885-4888Article in journal (Refereed)
    Abstract [en]

    Background: The cell cycle checkpoint kinase 2 (CHEK2) 1100delC variant has recently been identified at high frequency in families with both breast and colorectal cancer, suggesting the possible role of this variant in colorectal cancer predisposition. Patients and Methods: To evaluate the role of CHEK2 1100delC among Swedish colorectal cancer patients, the variant frequency was determined in 174 selected familial cases, 644 unselected cases and 760 controls, as well as in 18 families used in the genome-wide linkage analysis, where weak linkage was seen for the region harboring the CHEK2 gene. Results: CHEK2 1100delC was found in 1.15% of familial and in 0.93% of unselected cases, compared to 0.66% of controls, showing no significant difference between groups. One out of 45 familial cases with a family history of breast cancer was shown to be a carrier. The variant was not identified in the 18 families included in the linkage analysis. Conclusion: The CHEK2 1100delC was not significantly increased in Swedish colorectal cancer patients, however, in order to determine the role of the variant in colorectal cancer families with the history of breast cancer a larger sample size is needed.

  • 11. Edgren, M
    et al.
    Eriksson, Barbro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Wilander, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
    Westlin, J-E
    Nilsson, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Biological characteristics of adrenocortical carcinoma: A study of p53, IGF, EGF-r, Ki-67 and PCNA in 17 adrenocortical carcinomas1997In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 17, no 2B, p. 1303-1310Article in journal (Refereed)
    Abstract [en]

    Adrenocortical carcinoma (ACC) is a rare neoplasm with a poor prognosis. Prognostic factors are needed to identify patients who should be treated aggressively and those for which a less aggressive approach is warranted. As a result of advances within the field of immunohistochemistry, investigations of Ki-67, PCNA, IGF, EGF-r and p53 were performed in 17 ACC. The aim of this study was to clarify the role of Ki-67, PCNA, EGF-r, IGF and p53 in correlation to tumour behaviour and outcome. This retrospective study includes 16 patients, 10 women and 6 men, with a median age of 46 years. Nine tumours were hormonally functioning and 7 were non-functioning. The results obtained revealed that all tumours expressed PCNA and Ki-67 with median values of 59% and 14%, respectively, while p53 was negative in 88%, IGF negative in 82% and EGF-r positive in 94% of the tumours. No correlation was found between p53, IGF, EGF-r and survival rate. There was no interdependence between PCNA and Ki-67, or between PCNA, Ki-67 and the survival rate.

  • 12.
    Ekman, Simon
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Eriksson, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Bergström, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Johansson, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Goike, Helena
    Gullbo, Joachim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Henriksson, Roger
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Bergqvist, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Clinical value of using serological cytokeratins as therapeutic markers in thoracic malignancies2007In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 27, no 5B, p. 3545-3553Article, review/survey (Refereed)
    Abstract [en]

    In recent years, there has been an increasing awareness among physicians of the value of therapeutic interventions in patients suffering from lung cancer and mesothelioma. A search for an optimal approach using surgery, irradiation and chemotherapy in different settings of the tumour disease, including curatively aimed adjuvant chemotherapy after locoregional surgery or radiotherapy, has resulted in gradually improved survival rates. Still, early detection is crucial if there is to be a possibility of curing patients or prolonging life in cases of relapsed disease. Several studies have been initiated in which surrogate markers are evaluated in comparison to chest X-rays and computer tomography. The present review focuses on the predictive and prognostic value of using serological cytokeratins as tumour markers for patients suffering from thoracic malignancies.

  • 13. Eriksson, Mathilda
    et al.
    Hassan, Saadia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology.
    Larsson, Rolf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology.
    Linder, Stig
    Karolinska Institutet.
    Ramqvist, Torbjörn
    Lövborg, Henrik
    Vikinge, Trine
    Figgemeier, Egbert
    Müller, Jürgen
    Stetefeld, Jörg
    Dalianis, Tina
    Ozbek, Suat
    Utilization of a right-handed coiled-coil protein from archaebacterium Staphylothermus marinus as a carrier for cisplatin2009In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 29, no 1, p. 11-18Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    The nano-sized right-handed coiled-coil (RHCC) protein, originating from the archaebacterium Staphylothermus marinus, is stable at high salt concentrations, high temperatures, high pressures and extremes of pH. Its crystal structure reveals four hydrophobic cavities which can incorporate heavy metals. Nano-sized compounds have been used to carry cytotoxic drugs to tumours, avoiding delivery to healthy tissue, in part due to enhanced permeability in tumour blood vessels (enhanced permeability and retention effect).

    MATERIALS AND METHODS:

    The ability of RHCC to carry the platinum-containing chemotherapeutic drug cisplatin to cells, while retaining the cytotoxic potential was tested both in vitro and in vivo.

    RESULTS:

    RHCC was able to bind and enter cells in vitro and was not severely toxic or immunogenic in mice. Moreover, RHCC incorporated cisplatin, without inhibiting the cytotoxic potential of the drug against tumour cell lines in vitro or in vivo.

    CONCLUSION:

    RHCC can be used as a carrier of cisplatin without abrogating the effect of the drug.

  • 14.
    Falk Delgado, Alberto
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Plastic Surgery.
    Falk Delgado, Anna
    Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden..
    Complete Lymph Node Dissection in Melanoma: A Systematic Review and Meta-Analysis2017In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 37, no 12, p. 6825-6829Article, review/survey (Refereed)
    Abstract [en]

    Background: The aim of this meta-analysis was to estimate the survival after immediate complete lymph node dissection (CLND) compared to observation only (OO) or delayed CLND in patients with melanoma and lymph node metastasis.

    Materials and Methods: A systematic search was performed in: PubMed, Web of Science, Cochrane Library, CINAHL, Clinical trials and Embase. Eligible studies were randomized controlled trials (RCTs) comparing: CLND with OO, or immediate CLND with delayed CLND.

    Results: Four RCTs were included. There was no difference in melanoma-specific survival (MSS) (HR=0.91, 95% CI=0.77-1.08, p=0.29). In a sensitivity analysis, MSS was higher after immediate CLND compared to delayed CLND in patients with nodal metastasis (HR=0.63, 95% CI=0.35-0.74, p=0.0004) without evidence of heterogeneity.

    Conclusion: CLND appears to have no additional survival benefit after SNB compared to OO. However, subgroup analysis suggests a time-dependent benefit for early surgical lymph node removal compared to delayed or none.

  • 15.
    Falk Delgado, Alberto
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Plastic Surgery.
    Falk Delgado, Anna
    Karolinska Institute, Department of Clinical Neuroscience.
    Inconsistent Reporting Between Meta-analysis Protocol and Publication – A Cross-Sectional Study2017In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 37, no 9, p. 5101-5107Article in journal (Refereed)
    Abstract [en]

    Background: Inconsistent reporting in published meta-analyses compared to registered protocol are poorly understood. The aim of the study was to assess inconsistencies between registered protocols and published reports among oncology drug meta-analyses.

    Materials and Methods: A cross-sectional study was performed including oncology drug meta-analyses published between January 1st and November 14th 2016 with a published protocol. Two investigators extracted data on: selection criteria, outcome(s) and statistical plan in protocol and manuscript, plus self-acknowledgement of inconsistent reporting between protocol and publication.

    Results: Protocol registration was present in 19% (23/119) of all oncology drug meta-analyses. In meta-analyses with protocol (n= 23), 70% (16/23) had issues with inconsistent reporting between protocol and published report concerning; inclusion criteria, comparator group, intervention, outcome (PICO) or statistical analysis. Self-acknowledgement of changes between protocol and publication was found in 50% (8/16).

    Conclusion: In meta-analyses with protocol, discrepancies between registered protocols and publications are frequent.

  • 16. Gonterol, P.
    et al.
    Sylvester, R.
    Pisano, F.
    Joniau, S.
    Eeckt, Kathy Vander
    Serretta, V.
    Larre, S.
    di Stasi, S.
    Van Rhijn, B.
    Witjes, A.
    Grotenhuis, A.
    Colombo, R.
    Brigand, A.
    Babjukl, M.
    Soukupw, V.
    Malmström, Per-Uno
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Irani, J.
    Malats, N.
    Baniel, J.
    Mano, R.
    Cai, T.
    Cha, E.
    Ardelti, P.
    Vakarakisis, J.
    Bartoletti, R.
    Sphan, M.
    Dalbagnin, G.
    Shariat, S. F.
    Karnes, J.
    Palou, J.
    Prognostic Factors And Risk Groups In T1g3 Patients Initially Treated With Bcg: Results Of A Multicenter Retrospective Series In 1743 Patients2013In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 33, no 5, p. 2260-2261Article in journal (Other academic)
  • 17.
    Hakelius, Malin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Plastic Surgery.
    Koskela, Anita
    Ivarsson, Mikael
    Grenman, Reidar
    Rubin, Kristofer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Gerdin, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Plastic Surgery.
    Nowinski, Daniel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Plastic Surgery.
    Keratinocytes and Head and Neck Squamous Cell Carcinoma Cells Regulate Urokinase-type Plasminogen Activator and Plasminogen Activator Inhibitor-1 in Fibroblasts2013In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 33, no 8, p. 3113-3118Article in journal (Refereed)
    Abstract [en]

    Background: To investigate possible differences in the effects of soluble factors from oral squamous cell carcinoma (SCC) cells (UT-SCC-87) and normal oral keratinocytes (NOK) on fibroblast expression of genes involved in tumor stroma turnover. Materials and Methods: Transwell co-cultures with fibroblasts in collagen gels, and SCC cells or NOK in inserts were carried out. Fibroblast gene expression was measured with real-time polymerase chain reaction (PCR). Results: The expression of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) was up-regulated in co-cultures with SCC cells but not with NOK. In contrast, both SCC cells and NOK regulated matrix metalloproteinase-1 (MMP1) and -3, and tissue inhibitor of metalloproteinases-2 (TIMP2) and -3 to a similar extent, while MMP2 and TIMP1 were largely unaffected. Interleukin 1 alpha (IL1 alpha) up-regulated both MMP1 and MMP3 and down-regulated PAI-1, TIMP2 and -3. Conclusion: SCC and NOK regulate fibroblast expression of genes involved in tumor stroma turnover differentially in vitro. These observations may contribute to a better understanding of the mechanisms behind extracellular matrix turnover in tumors.

  • 18.
    Hakelius, Malin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Plastic Surgery.
    Reyhani, Vahid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Rubin, Kristofer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Gerdin, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Plastic Surgery.
    Nowinski, Daniel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Plastic Surgery.
    Normal oral keratinocytes and head and neck squamous carcinoma cells induce an innate response in fibroblasts2016In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 36, no 5, p. 2131-2137Article in journal (Other academic)
    Abstract [en]

    Background: Tumor stroma is similar to the connective tissue of chronic inflammation. The extracellular matrix of tumors is formed by cancer-associated fibroblasts that also modulate the inflammatory response. Materials and Methods: We studied the ability of oral keratinocytes (NOK) and oral squamous cell carcinoma cells (SCC) to induce an innate immune response in fibroblasts. Co-cultures with fibroblasts in collagen gels and keratinocytes in inserts were used. Pentraxin 3 (PTX3) was used as an indicator of an innate immune response. Results: SCC and NOK up-regulated fibroblast mRNA expression and protein release of PTX3. mRNA levels were more pronounced in cultures with malignant cells. The induction of PTX3 was abrogated by an interleukin-1 receptor antagonist Conclusion: Keratinocytes have the capacity to induce an interleukin-1-dependent innate immune response by fibroblasts in vitro. This could be important for subsequent fibroblast modulation of the inflammatory reaction in non-malignant and malignant disease processes.

  • 19.
    Hakelius, Malin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Plastic Surgery.
    Saiepour, Daniel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Plastic Surgery.
    Göransson, Hanna Kultima
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Rubin, Kristofer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Gerdin, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Plastic Surgery.
    Nowinski, Daniel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Plastic Surgery.
    Differential Gene Regulation in Fibroblasts in Co-culture with Keratinocytes and Head and Neck SCC Cells2015In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 35, no 6, p. 3253-3265Article in journal (Refereed)
    Abstract [en]

    Background: While carcinoma-associated fibroblasts (CAFs) support tumorigenesis, normal tissue fibroblasts suppress tumor progression. Mechanisms behind conversion of fibroblasts into a CAF phenotype are largely unrevealed. Materials and Methods: Transwell co-cultures with fibroblasts in collagen gels and squamous-cell carcinoma (SCC) cells or normal oral keratinocytes (NOKs) in inserts. Differences in fibroblast global gene expression were analyzed using Affymetrix arrays and subsequent functional annotation and cluster analysis, as well as gene set enrichment analysis were performed. Results: There were 52 up-regulated and 30 down-regulated transcript IDs (>2-fold, p<0.05) in fibroblasts co-cultured with SCC compared to NOKs. Functional analysis demonstrated an enrichment of collagen-related genes. There were similarities with gene sets reflecting a non-specific, innate-type response with activation of both interferon pathways and connective tissue turnover. Conclusion: There were distinct differences in fibroblast gene expression between the co-culture types. Many were in genes related to an innate-type of response and to connective tissue turnover.

  • 20.
    Hassan, Saadia B.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology.
    Lövborg, Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology.
    Lindhagen, Elin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology.
    Karlsson, Mats O.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences, Division of Pharmacokinetics and Drug Therapy.
    Larsson, Rolf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology.
    CHS 828 kill tumour cells by inhibiting the nuclear factor-kappa B translocation but unlikely through down-regulation of proteasome2006In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 26, no 6B, p. 4431-4436Article in journal (Refereed)
    Abstract [en]

    CHS 828 (N-(6-chlorophenoxyhexyl)-N'cyano-N"-4-pyridylguanidine) has shown promising activity in many preclinical systems and in phase I/II clinical trials. The nuclear transcription factor kappa B (NF-κB) has been identified as a target for CHS 828. The aim of this study was to confirm the inhibitory effect of CHS 828 on NF-κB translocation and to explore its possible effect on the proteasome using 7 cell lines. Translocation of NF-κB from the cytoplasm to the nucleus was analysed using a quantitative cytometric system, ArrayScan®. The activity of the proteasome was assayed by monitoring the hydrolysis of a fluorogenic substrate. In parallel, the in vitro cytotoxic effect of CHS 828 was analyzed using a 72-h microtiter plate-based cytotoxicity assay (FMCA). CHS 828 inhibited NF-κB translocation in the cell lines where it was able to inhibit the tumour cell growth. However, the results did not prove any effect of CHS 828 on proteasome activity when compared to a proteasome inhibitor activity.

  • 21.
    Hassan, Saadia Bashir
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology.
    Gali-Muhtasib, Hala
    Göransson, Hanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology.
    Larsson, Rolf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology.
    Alpha Terpineol: A Potential Anticancer Agent which Acts through Suppressing NF-kappa B Signalling2010In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 30, no 6, p. 1911-1919Article in journal (Refereed)
    Abstract [en]

    Background:

    Alpha terpineol is a bioactive component of Salvia libanotica essential oil extract and has shown antitumour activity.

    Materials and Methods:

    The cytotoxicity of alpha terpineol towards different tumour cell lines was evaluated in vitro. Mechanistic characterization was performed using analysis of drug activity in a cell line panel and drug-induced gene expression perturbation using the connectivity map approach.

    Results:

    The small cell lung carcinoma was the cell line most sensitive to alpha terpineol. The results proposed alpha terpineol as an NF-kappa B inhibitor, which was confirmed by the observed dose-dependent inhibition of NF-kappa B translocation and activity using two NF-kappa B assays, and by the down-regulation of the expression of several NE-kappa B-related genes such as IL-1 beta and IL1R1.

    Conclusion:

    The results suggest that alpha terpineol inhibits the growth of tumour cells through a mechanism that involves inhibition of the NF-kappa B pathway.

  • 22.
    Hassan, Saadia Bashir
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine.
    Gullbo, Joachim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine.
    Hu, Kefei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Virology.
    Berenjian, Saideh
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Virology.
    Morein, Bror
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Virology.
    Nygren, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    The Nanoparticulate Quillaja Saponin BBE Is Selectively Active Towards Renal Cell Carcinoma2013In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 33, no 1, p. 143-151Article in journal (Refereed)
    Abstract [en]

    Aim: To characterize the cytotoxic effect of BBE, the particulate of desacyl-saponin, in model systems of solid tumours. Materials and Methods: Cytotoxic activity of BBE was investigated in solid human tumour cell lines, in tumour cells from patients with renal cell carcinoma, in normal human renal cells and in peripheral blood mononuclear cells. The BBE mode of cell death was assessed in vitro. In vivo effect of BBE was evaluated in xenograft-bearing mice. Results: BBE was selectively active against renal cell carcinoma, with no or little effect on normal cells. BBE induced caspase activity and apoptosis. An inhibitory activity of BBE on xenograft tumour growth, with no apparent signs of haematological toxicity was shown. In the non-proliferative model of patient tumour cells, BBE was active on only 1/5 patient samples, suggesting association of BBE effect with cell proliferation. Conclusion: BBE has interesting activities against renal cell carcinoma and should be further explored as a drug against this resistant tumour type.

  • 23. Hedman, Mattias
    et al.
    Bergqvist, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Brattström, Daniel
    Brodin, Ola
    Fractionated Irradiation of Five Human Lung Cancer Cell Lines and Prediction of Survival According to a Radiobiology Model2011In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 31, no 4, p. 1125-1130Article in journal (Refereed)
    Abstract [en]

    Background: This study evaluates a predictive radiobiology model by measurements of surviving fraction (SF) by the clonogenic assay or the extrapolation method and the proliferation rate in vitro. It is hypothesized that incorporating proliferation to intrinsic radiosensitivity, measured by SF, to predict radiation responsiveness after fractionated irradiation adds to the model's accuracy. Materials and Methods. Five lung cancer cell lines with known SF after 1 Gy (SF1), and also SF2 and SF5, were irradiated with three different fractionation regimes; 10x1 Gy, 5x2 Gy or 2x5 Gy during the same total time to achieve empirical SF. In addition, the SF1, SF2 and SF5 after fractionated irradiation was calculated for each cell line based on the already known single fraction SF and with or without a proliferation factor. The results were compared to the empirical data. Results and Discussion: By using the clonogenic assay to measure radiosensitivity, prediction of radiosensitivity was improved after fractionated radiotherapy when proliferation was used in the radiobiology model. However, this was not the case in the cell lines where the extrapolation method was used to calculate SF. Thus, a radiobiology model including intrinsic radiosensitivity, measured by the clonogenic assay, as well as proliferation, is better at predicting survival after fractionated radiotherapy, compared to the use of intrinsic radiosensitivity alone.

  • 24.
    Hellberg, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Center for Clinical Research Dalarna.
    Sex Steroids and Cervical Cancer2012In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 32, no 8, p. 3045-3054Article, review/survey (Refereed)
    Abstract [en]

    During the 19th century, studies indicated that reproductive events were involved in cervical cancer. Human papillomavirus (HPV) infection is a prerequisite for development of cancer, but co-factors, among them the action of sexual steroid hormones, are necessary. Childbirth has been an important risk factor but now probably plays a minor role in the industrialized world, where parity is low. Longterm oral contraceptive use has been thoroughly studied epidemiologically, and correlates to cervical cancer in most studies. In vitro studies on cervical cell lines transfected with HPV and animal studies indicate that sex steroid hormones are capable to induce cancer. In in vivo cervical cancer tissue studies there have been observations that endogenous progesterone in serum correlates to a negative pattern of expression of cellular and extracellular proteins, tumor markers. Immune response could be another mechanism. Estradiol might be associated with a positive pattern and high estradiol and low progesterone levels increase duration of survival in cervical cancer. Studies where treatment of compounds that influence sex steroid hormones have been given are rare and have been disappointing.

  • 25.
    Hellberg, Dan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Tot, Tibor
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Tumor Marker Score for Prognostication of Early-stage Squamous Cell Cervical Cancer2014In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 34, no 2, p. 887-892Article in journal (Refereed)
    Abstract [en]

    Background/Aim: Histopathological and clinical scores to predict prognosis in cervical cancer have been of limited value. In the present study a tumor marker expression score was evaluated for prognostication in early-stage cervical cancer. Materials and Methods: The entire study population included 128 women with invasive squamous cell cervical cancer followed-up for at least 10 years. Results: Expression of 12 tumor markers (epidermal growth factor receptor (EGFR), Ki-67, c-MYC, p53, p27, E-cadherin, CD44, vascular endothelial growth factor receptor (VEGF), cyclooxygenase-2 (COX2), CD4, and leucine-rich immunoglobulin-like repeats-1 (LRIG1) and LRIG2, considered relevant for cervical cancer prognostication was evaluated by immunohistochemistry. Expression of five markers, LRIG1, LRIG2, p53, COX2 and c-MYC were useful to make a prognostication score, ranging from 0 to 5. Score 0-1 correlated to less than 5% 10-year mortality, while the mortality rate of those with score 4-5 approached 70%; those with score 2 formed an intermediate group. Using different models, a high sensitivity, specificity, positive predictive value and negative predictive value was attained. Conclusion: Tumor marker scoring could be an adjunct to histopathological and clinical parameters in prognostication of early-stage cervical cancer.

  • 26.
    Hellberg, Dan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Tot, Tibor
    Stendahl, Ulf
    Differences in expression of tumor markers between pre- and postmenopausal women with invasive cervical cancer2008In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 28, no 3B, p. 1793-1795Article in journal (Refereed)
    Abstract [en]

    The aim of the present study was to investigate the differences in the expression of tumor markers in squamous cell and in adenomatous carcinomas in pre- and postmenopausal women, respectively. Patients and Methods: The study population comprised 53 premenopausal and 107 postmenopausal women. Thirty-four tumors were adenomatous (n=31) or adenosquamous carcinomas (n=3), distributed between 13 premenopausal and 21 postmenopausal women. The remaining 126 squamous cell carcinomas were diagnosed in 40 pre- and 86 postmenopausal women. Expression of ten tumor markers of possible clinical importance in cervical cancer was evaluated. Results: Expression of three tumor markers, p53 (> ;0% vs. 0%), p27 (> , 20% vs. < ;20%) and cyclooxygenase-2 (COX-2) (high intensity vs. moderate/none) differed significantly between pre- compared to postmenopausal women with squamous cell (p27, 54% vs. 72%, p=0.009) or adenomatous carcinomas (p53, 8% vs. 63%, p=0.006 and COX-2, 46% vs. 20%, p=0.03). All results were adjusted for clinical cancer stage. Conclusion: The unusual age-specific incidence curve in cervical cancer has rarely been related to expression of tumor markers. Age-related differences in expression of tumor markers could reflect some age-related different biological mechanisms in cervical cancer.

  • 27.
    Hillbertz, Nicolette Salmon
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    Hirsch, Jan-Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    Jalouli, Jamshid
    Jalouli, Miranda M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    Sand, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    Viral and Molecular Aspects of Oral Cancer2012In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 32, no 10, p. 4201-4212Article, review/survey (Refereed)
    Abstract [en]

    Squamous cell carcinoma (SCC) is the most common epithelial malignancy in the oral cavity. SCCs and their variants constitute over 90% of oral malignancies, and the disease is associated with poor prognosis. OSCC is a complex malignancy where environmental factors, virus infections, and genetic alterations most likely interact, and thus give rise to the malignant condition. Herein, we review the available literature regarding high-risk factors such as alcohol and tobacco usage; discuss the roles of human papillomaviruses (HPV), the Epstein-Barr virus, and the human herpes simplex virus (HSV); and evaluate several candidate genes associated with the condition: p53, p16(INK4) and p21(WAF1/CIP1) survivin, B-cell lymphoma-2 (BCL-2), keratins, Fibroblast growth factor 3 (FGF3), FGF4, FGF19, Oral cancer overexpressed gene 1 (ORAOV1), and Cyclin D1 (CCND1).

  • 28.
    Hirsch, Jan-Michael
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    Wallström, Mats
    Carlsson, Anders-Petter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    Sand, Lars P
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    Oral cancer in Swedish snuff dippers2012In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 32, no 8, p. 3327-3330Article in journal (Refereed)
    Abstract [en]

    Over recent decades there has been debate over whether or not Swedish snuff is carcinogenic in humans. Animal studies and molecular biological and experimental studies have shown the carcinogenic potential of Swedish snuff, but this has not been proved in prospective randomized studies. We present a case series of patients with oral squamous cell carcinomas diagnosed at the sites where the patients had used Swedish snuff for several years. Sixteen male patients were referred to and treated at Oral and Maxillofacial Surgery Departments and Ear, Nose and Throat clinics at seven different hospitals in Sweden. The mean age of the patients at the time of diagnosis was 72.9 years and the mean time of snuff use prior to cancer diagnosis was 42.9 years. This case series shows that Swedish snuff may not be a harmless alternative to smoking.

  • 29.
    Holgersson, Georg
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg. Gavle Cent Hosp, Dept Oncol, SE-80187 Gavle, Sweden..
    Bergström, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg. Gavle Cent Hosp, Dept Oncol, SE-80187 Gavle, Sweden..
    Liv, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
    Nilsson, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg. Gavle Cent Hosp, Dept Oncol, SE-80187 Gavle, Sweden..
    Edlund, Per
    Gavle Cent Hosp, Dept Oncol, SE-80187 Gavle, Sweden..
    Blomberg, Carl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg. Gavle Cent Hosp, Dept Oncol, SE-80187 Gavle, Sweden..
    Nyman, Jan
    Sahlgrens Univ Hosp, Dept Oncol, Gothenburg, Sweden..
    Friesland, Signe
    Karolinska Univ Hosp, Dept Oncol, Stockholm, Sweden..
    Ekman, Simon
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Asklund, Thomas
    Umea Univ Hosp, Dept Radiat Sci & Oncol, S-90185 Umea, Sweden..
    Henriksson, Roger
    Umea Univ Hosp, Dept Radiat Sci & Oncol, S-90185 Umea, Sweden..
    Bergqvist, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg. Umea Univ Hosp, Dept Radiat Sci & Oncol, S-90185 Umea, Sweden..
    Effect of Increased Radiotoxicity on Survival of Patients with Non-small Cell Lung Cancer Treated with Curatively Intended Radiotherapy2015In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 35, no 10, p. 5491-5497Article in journal (Refereed)
    Abstract [en]

    Aim: To elucidate the impact of different forms of radiation toxicities (esophagitis, radiation pneumonitis, mucositis and hoarseness), on the survival of patients treated with curatively intended radiotherapy for non-small cell lung cancer (NSCLC). Patients and Methods: Data were individually collected retrospectively for all patients diagnosed with NSCLC subjected to curatively intended radiotherapy (>= 50 Gy) in Sweden during the time period 1990 to 2000. Results: Esophagitis was the only radiation-induced toxicity with an impact on survival (hazard ratio=0.83, p=0.016). However, in a multivariate model, with clinical-and treatment-related factors taken into consideration, the impact of esophagitis on survival was no longer statistically significant (hazard ratio=0.88, p=0.17). Conclusion: The effect on survival seen in univariate analysis may be related to higher radiation dose and to the higher prevalence of chemotherapy in this group. The results do not suggest that the toxicities examined have any detrimental effect on overall survival.

  • 30.
    Holgersson, Georg
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Sandelin, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Hoye, Even
    Bergström, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , Centre for Research and Development, Gävleborg.
    Henriksson, Roger
    Ekman, Simon
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Nyman, Jan
    Helsing, Martin
    Friesland, Signe
    Brodin, Ola
    Holgersson, Margareta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Lamberg Lundström, Kristina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Janson, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Respiratory Medicine and Allergology.
    Ekberg, Lars
    Morth, Charlotte
    Blystad, Thomas
    Ewers, Sven-Borje
    Loden, Britta
    Bergqvist, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    The Value of Induction Chemotherapy for Survival in Patients with Non-small Cell Lung Cancer Treated with Radiotherapy2012In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 32, no 4, p. 1339-1346Article in journal (Refereed)
    Abstract [en]

    Aim: The aim of the present study was to retrospectively investigate the impact of induction chemotherapy on treatment outcome in patients treated with curatively intended radiotherapy for non-small cell lung cancer (NSCLC). Patients and Methods: Patients with a diagnosed NSCLC that have been subjected to curatively intended irradiation (>= 50 Gy) and treated in an oncology department in Sweden during the years 1990-2000 were included in the study. Operated patients and patients having received concomitant chemotherapy were excluded. The included patients were localised by a manual search of all the oncology departments' medical records and radiation charts. Results: Patients treated with induction chemotherapy (n=79) had a significantly better overall survival compared with patients treated with radiotherapy alone (p=0.0097) in a univariate Cox regression analysis. A platinum/taxane combination produced the greatest survival benefit; hazard ratio=0.49 (95% confidence interval=0.31 to 0.75). Conclusion: We found that patients treated with induction chemotherapy in addition to radiotherapy for NSCLC have a better overall survival than patients treated with radiotherapy alone and that the best results are achieved using a platinum/taxane combination.

  • 31.
    Jalouli, Jamshid
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    Jalouli, Miranda M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    Sapkota, Dipak
    Ibrahim, Salah O.
    Larsson, Per-Anders
    Sand, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    Human Papilloma Virus, Herpes Simplex Virus and Epstein Barr Virus in Oral Squamous Cell Carcinoma from Eight Different Countries2012In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 32, no 2, p. 571-580Article in journal (Refereed)
    Abstract [en]

    Oral squamous cell carcinoma (OSCC) is a major health problem in many parts of the world, and the major causative agents are thought to he the use of alcohol and tobacco. Oncogenic viruses have also been suggested to be involved in OSCC development. This study investigated the prevalence of human papillomaviruses (HPV), herpes simplex virus (HSV) and Epstein-Barr virus (EBV) in 155 OSCC from eight different countries from different ethnic groups, continents and with different socioeconomic backgrounds. 41 A total of OSCCs were diagnosed in the tongue (26%) and 23 in the floor of the mouth (15%); the other 91 OSCCs were diagnosed in other locations (59%). The patients were also investigated regarding the use of alcohol and smoking and smokeless tobacco habits. Tissue samples were obtained from formalin-fixed, paraffin-embedded samples of the OSCC. DNA was extracted and the viral genome was examined by single, nested and seminested PCR assays. Sequencing of double-stranded DNA from the PCR product was carried out. Following sequencing of the HPV-, HSV- and EBV-positive PCR products, 100% homology between the sampels was found. Of all the 155 OSCCs examined, 85 (55%) were positive for EBV, 54 (35%) for HPV and 24 (15%) for HSV. The highest prevalence of HPV was seen in Sudan (65%), while HSV (55%) and EBV (80%) were most prevalent in the UK. In 34% (52/155) of all the samples examined, co-infection by two (46/155=30%) or three (6/155=4%) virus specimens was detected. The most frequent double infection was HPV with EBV in 21% (32/155) of all OSCCs. There was a statistically significant higher proportion of samples with HSV (p=0.026) and EBV (p=0.015) in industrialized countries (Sweden, Norway, UK and USA) as compared to developing countries (Sudan, India, Sri Lanka and Yemen). Furthermore, there was a statistically significant higher co-infection of HSV and EBV in samples from industrialized countries (p=0.00031). No firm conclusions could be drawn regarding the relationship between alcohol, tobacco and virus infections. The significance of our findings must be put in relation to other risk factors and these observations warrant further studies to determine the possible role of viral infections and co-infections with HPV, EBV and HSV as risk markers for the development of OSCC.

  • 32.
    Jalouli, Miranda M.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    Jalouli, Jamshid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    Sapkota, Dipak
    Ibrahim, Salah O.
    Sand, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    Hirsch, Jan-M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    Differential Expression of Apoptosis, Cell Cycle Regulation and Intermediate Filament Genes in Oral Squamous Cell Carcinomas Associated with Toombak Use in Sudan2011In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 31, no 10, p. 3345-3351Article in journal (Refereed)
    Abstract [en]

    Previously we used microarray genomic hybridization technology to explore genome-wide profiles of chromosomal aberrations in samples of oral squamous cell carcinomas (OSCCs) and paired normal controls. Based on these findings, 9 genes related to apoptosis, cell cycle regulation and intermediate filament proteins were selected and their differential expression status was examined by real-time quantitative RT-PCR in 26 samples of Sudanese OSCCs and their matched normal controls. The findings were correlated with the habit of toombak use. The mRNA levels of Bcl2, keratin 1, keratin 13 and p53 were significantly lower and the level of survivin was significantly higher in the OSCC samples of the toombak users compared to their paired control samples. A significant down-regulation in keratin I and keratin 13 expression levels was found in the OSCC samples of the non-toombak users compared to their normal control samples. The differential expression of genes related to apoptosis, cell cycle regulation and types I and II keratin could be useful diagnostic markers and provide valuable information for the understanding of oral malignancy in relation to toombak use.

  • 33. Jawert, Fredrik
    et al.
    Hasseus, Bengt
    Kjeller, Goran
    Magnusson, Bengt
    Sand, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Oral and Maxillofacial Surgery.
    Larsson, Lena
    Loss of 5-Hydroxymethylcytosine and TET2 in Oral Squamous Cell Carcinoma2013In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 33, no 10, p. 4325-4328Article in journal (Refereed)
    Abstract [en]

    Aim: Epigenetic modifications, such as DNA methylation, are considered important in the regulation of target genes in cancer development. 5-Hydroxymethylcytosine (5hmC) was recently discovered to be related to the process of malignant transformation. The influence of DNA methylation in oral squamous cell carcinomas (OSCC) is not fully- understood. Therefore, the aim of the present study was to investigate the DNA methylation pattern in OSCC compared to healthy oral epithelium. Materials and Methods: Oral mucosal samples from patients with OSCC (n=15) and healthy mucosa (n=12) were analyzed using immunohistochemistry with antibodies against 5hmC, 5mC and ten-eleven-translocation-2 (TET2). Results: A significant decrease in 5hmC and TET2 expression was found in OSCC compared to healthy oral epithelium. In contrast, there was a significant increase in 5mC expression in OSCC compared to healthy epithelium. Conclusion: Our results indicate that loss of 5hmC is an epigenetic event of OSCC.

  • 34.
    Johansson, Andreas K.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Radiation Science.
    Lennernäs, Bo
    Isacsson, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Radiation Science.
    Neurovascular Bundle Infiltration Can Explain Local Relapses Using Conformal Radiotherapy of Prostate Cancer.2017In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 37, no 4, p. 1825-1830Article in journal (Refereed)
    Abstract [en]

    AIM: To quantify the impact of decreased margins for two treatment techniques, three-dimensional conformal radiotherapy (3D-CRT) and volumetric-modulated arc therapy (VMAT), on local control in curative treatment of prostate cancer.

    MATERIALS AND METHODS: The planning target volume (PTV) margins were decreased in steps of 1 mm from 10 to 1 mm. Treatment plans using 3D-CRT and VMAT technique were produced for all margin sizes and the dose to the neuro vascular bundles (NVB), that was not included in the PTV, was investigated.

    RESULTS: Due to the more conformal dose delivery using VMAT, the dose to the NVB decreased more rapidly by VMAT compared to the 3D-CRT plans. The dose difference was significant for margins from 1-7 mm.

    CONCLUSION: One should be very cautious before clinical routines are changed, bearing in mind whether the change means more conformal treatment technique, smaller margins or target segmentation in different imaging modalities.

  • 35.
    Johansson, Fredrik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Ekman, Simon
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Blomquist, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Henriksson, Roger
    Bergström, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
    Bergqvist, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    A Review of Dose-dense Temozolomide Alone and in Combination with Bevacizumab in Patients with First Relapse of Glioblastoma2012In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 32, no 9, p. 4001-4006Article, review/survey (Refereed)
    Abstract [en]

    Treatment of patients with glioblastoma improved dramatically when concomitant and adjuvant temozolomide was added to external radiation therapy. The addition of this new treatment schedule as well as the improvements in individually-tailored radiation treatment, has resulted in a larger proportion of patients being fit for further treatment after first relapse. One of the most interesting combinations that have started to become part of the therapeutic arsenal in the daily clinic is dose-dense temozolomide in combination with bevacizumab. We reviewed and compiled the literature concerning the present topic based on a search of the PubMed database (http://www.ncbi.nlm.nih.gov/pubmed/) for the years between 1995 and 2011. The clinical studies that have been performed are small and divergent, making it difficult to grade the scientific evidence for the combinatorial treatment of dose-dense temozolomide and bevacizumab. However, the available studies and the experience we have at our departments suggest that this combination is of interest for glioblastoma patients experiencing first relapse. More randomized clinical trials are needed in order to establish the standard of treatment at first relapse in patients with glioblastoma.

  • 36.
    Kindler, Csaba
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Smedh, Kennet
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Chabok, Abbas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Shetye, Jayant
    Department of Pathology, Vastmanland's Hospital Vasteras, Vasteras, Sweden.
    Dafnis, George
    Malar Hosp, Dept Surg, Eskilstuna, Sweden..
    Nikberg, Maziar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
    Detection of Free Cancer Cells in Pelvic Lavage with Double Immunocytochemistry at Rectal Cancer Surgery2017In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 37, no 4, p. 1563-1568Article in journal (Refereed)
    Abstract [en]

    Background/Aim: The aim of the present study was to describe a double immunocytochemical staining method for detecting free cancer cells after rectal cancer surgery and to evaluate their extent and prognostic role. Materials and Methods: Immunocytochemistry was performed using antibodies against cytokeratin 20/caudal-typehomeobox transcription factor 2 (CDX2) and mucin glycoprotein-2 (MUC2)/p53 protein. The study included 29 patients with infraperitoneal rectal cancer who underwent bowel resection and four controls. The pelvic lavage was retrieved at the start of laparotomy, after total mesorectal excision and after abdominal lavage with sterile water. Results: Free cancer cells were detected with the double immunocytochemical method in the two controls with carcinomatosis and one control with sigmoidal cancer. None of the patients with rectal tumours had presence of free cancer cells. Conclusion: Immunocytochemical analysis of peritoneal lavage was feasible and negative in patients with infraperitoneal rectal cancer. Further studies are encouraged to investigate the clinical relevance in cases with free cancer cells after incomplete total mesorectal excision.

  • 37.
    Koyi, Hirsh
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg. Gavle Cent Hosp, Dept Resp Med, S-80187 Gavle, Sweden.;Karolinska Inst, Stockholm, Sweden..
    Hillerdal, Gunnar
    Gavle Cent Hosp, Dept Resp Med, S-80187 Gavle, Sweden.;Karolinska Univ Hosp, Dept Resp Med & Allergy, Stockholm, Sweden..
    Kölbeck, Karl-Gustav
    Karolinska Univ Hosp, Dept Resp Med & Allergy, Stockholm, Sweden..
    Brodin, Daniel
    Karolinska Univ Hosp, Dept Resp Med & Allergy, Stockholm, Sweden..
    Liv, Per
    Uppsala Univ, Cty Council Gavleborg, Ctr Res & Dev, Gavle, Sweden..
    Brandén, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg. Gavle Cent Hosp, Dept Resp Med, S-80187 Gavle, Sweden.;Karolinska Inst, Stockholm, Sweden..
    Non-small Cell Lung Cancer (NSCLC) in Octogenarians in Clinical Practice2016In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 36, no 10, p. 5397-5402Article in journal (Refereed)
    Abstract [en]

    Background/Aim: Globally, an increasing proportion of cancer patients are aged >65 years and many are aged >70 years. Treatment of the elderly with lung cancer has, therefore, become an important issue. We performed a retrospective study of our patients to demonstrate how octogenarians with non-small cell lung cancer (NSCLC) are treated in real-life clinical practice. Patients and Methods: This was a retrospective observational study of all elderly (>= 80 years) patients with NSCLC referred to the Department of Respiratory Medicine and Allergy, Karolinska Hospital, Sweden, 2003-2010, and followed until June, 2016. Results: In total, 452 patients, 216 (47.8%) men and 236 (52.2%) women, were included. The mean and median age was 83 years; 28 (6.2%) were aged 90 years or more. Current or former smokers constituted 91.1%, with men having smoked more (p<0.001). There was no difference in performance status (PS) between genders with PS 0-1 in 45.4%, PS 2 in 25.6% and PS3-4 in 29%. About a third each was diagnosed in stages 1-II, III and IV. Adenocarcinoma was most common (45.6%), 18.1% had squamous cell carcinoma, while histological diagnosis was unavailable in 23.2%. Best supportive care (BSC) was given only to 209 patients (46.2%). Potentially curative therapy was administered to 16.5% of men and 20.3% of the women with surgery performed in 35 patients (7.8%) and stereotactic body radiation therapy (SBRT) in 48 patients (10.6%). Chemotherapy was given to 51 patients (11.2%) and palliative radiotherapy to 77 (17.0%). Second-line chemotherapy was given in 4% and third-line in 1.5%. Only one patient received fourth-line. Male patients who received chemotherapy survived a mean of 281 days and for female patients it was 332 days (not significant). Median overall survival (OS) was 115 days in patients receiving BSC and 362 days in patients given any therapy. Patients who underwent surgery for stage I-II had a median OS of 5.6 years compared to 3.5 years for patients given SBRT. Conclusion: Treatment of NSCLC patients 80 years and older with any modality is feasible with a good PS. Survival is fairly good with surgery or SBRT.

  • 38.
    Larsson, Dhana E.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lövborg, Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology.
    Rickardson, Linda
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology.
    Larsson, Rolf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Granberg, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Identification and evaluation of potential anti-cancer drugs on human neuroendocrine tumor cell lines2006In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 26, no 6B, p. 4125-4129Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to investigate drug sensitivity in neuroendocrine tumor cell lines. Materials and Methods: In vitro drug sensitivity screening was performed using the fluorometric microculture cytotoxicity assay in one human pancreatic carcinoid and two human bronchial carcinoid cell lines. In addition, a normal human retinal pigment epithelial cell line was used for comparison. A total of 18 drugs with different mechanisms of action were tested. Results: The most active agents were brefeldin A, emetine, bortezomib and idarubicin, having IC50 values < 1 μM in all four cell lines. In addition, the three tumor cell lines showed sensitivity for sanguinarine, Bay11-7085, mitoxantrone, doxorubicin, β-lapachone, NSC 95397 and CGP-74514A. Conclusion: The cell lines were sensitive for several drugs acting in different ways, covering a broad spectrum of mechanisms of action. Some of these compounds may possibly be used in clinical trials and show therapeutic effect in patients with neuroendocrine tumors.

  • 39.
    Larsson, Dhana E.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Wickström, Malin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology.
    Hassan, Sadia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Granberg, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    The Cytotoxic Agents NSC-95397, Brefeldin A, Bortezomib and Sanguinarine Induce Apoptosis in Neuroendocrine Tumors In Vitro2010In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 30, no 1, p. 149-156Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to investigate the apoptosis resulting from NSC 95397, brefeldin A, bortezomib and sanguinarine in neuroendocrine tumor cell lines. Materials and Methods: A multiparametric high-content screening assay for measurement of apoptosis was used. The human pancreatic carcinoid cell line, BON-1, human typical bronchial carcinoid cell line NCI-H727 and the human atypical bronchial carcinoid cell line NCI-H720 were tested. After incubation with cytotoxic drugs, the DNA-binding dye Hoechst 33342, fluorescein-tagged probes that covalently bind active caspase-3 and chloromethyl-X-rosamine to detect mitochondrial membrane potential were added. Image acquisition and quantitative measurement of fluorescence was performed using automated image capture and analysis instrument ArrayScan. In addition, nuclear morphology was examined on microscopic slides stained with May-Grunewald-Giemsa. Results: A time- and dose-dependent activation of caspase-3 and increase in nuclear fragmentation and condensation were observed for the drugs using a multiparametric apoptosis assay. These results were confirmed with nuclear morphological examination on microscopic slides. Conclusion: NSC 95397, brefeldin A, bortezomib and sanguinarine induced caspase-3 activation with modest changes in nuclear morphology.

  • 40. Larsson, P A
    et al.
    Sandros, J
    Vahlne, A
    Hirsch, Jan M
    University of Göteborg, Sweden.
    Stenman, G
    Non-random chromosome rearrangements in herpes simplex virus type 1 transformed diploid CHEF cells1992In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 12, no 3, p. 863-868Article in journal (Refereed)
    Abstract [en]

    The effects of Herpes simplex virus type 1 (HSV-1) on diploid, non-tumourigenic Chinese hamster embryo fibroblasts (CHEF/18-1D-3) were studied. Six independent lines transformed by HSV-1 alone or by HSV-1 in combination with acyclovir or aqueous tobacco extract were isolated. In contrast to uninfected CHEF/18-1D-3 cells, all transformants grew in soft agar and were tumourigenic in nude mice. Neither infectious virus nor viral antigens could be detected in any of the lines. Cytogenetic analysis revealed clonal chromosome abnormalities in all lines including trisomy for the long arm of chromosome 3 in five lines. In three of these the extra 3q was translocated onto 6p. All lines showed loss of the corresponding 3p arm. The remaining line had a hypodiploid stemline with loss of one chromosome 7. This line also showed a pronounced chromosomal instability with a multitude of mainly sporadic rearrangements. These results show that HSV-1 induced transformation and tumourigenesis in CHEF cells is associated with the induction of chromosome rearrangements, in particular trisomy for 3q.

  • 41.
    Laurell, Helena
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Hansson, Lars Erik
    Gunnarsson, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Why do surgeons miss malignancies in patients with acute abdominal pain?2006In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 26, no 5B, p. 3675-3678Article in journal (Refereed)
    Abstract [en]

    Background: The aim of this study was to characterize patients seeking medical advice for acute abdominal pain who were later diagnosed with an intra-abdominal malignancy. Patients and Methods: Patients with acute abdominal pain were registered between 1997 and 2000, employing a detailed schedule comprising 111 parameters. The diagnoses (n =2395 patients) were re-evaluated one year later. Results: A total of 66 patients (2.8%) were found to have an intra-abdominal malignancy at follow-up, of whom 37 cases had been undetected at discharge. Malignancy of the liver, biliary tract and pancreas constituted 30% and colorectal cancer 32% of the tumours undetected at discharge. Constipation, intestinal obstruction and non-specific abdominal pain (NSAP) were the most common preliminary diagnoses in patients among whom abdominal malignancy was later detected. Conclusion: Except for age and pain duration, the history and clinical investigation provide few clues to suggest an abdominal malignancy in patients with acute abdominal pain. NSAP, of unknown or known etiology, including constipation, should be suspected as a possible sign of abdominal malignancy in all patients over 50 years of age.

  • 42.
    Laytragoon-Lewin, Nongnit
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Bahram, Fuad
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Rutqvist, Lars Erik
    Turesson, Ingela
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Lewin, Freddi
    Direct Effects of Pure Nicotine, Cigarette Smoke Extract, Swedish-type Smokeless Tobacco (Snus) Extract and Ethanol on Human Normal Endothelial Cells and Fibroblasts2011In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 31, no 5, p. 1527-1534Article in journal (Refereed)
    Abstract [en]

    The adverse health effects of cigarette smoking are well established including the increased risk of various types of cancer. In this study, the direct effects of ethanol, pure nicotine, cigarette smoke extract and Swedish type smokeless tobacco (Snus) extract on normal cells were investigated. Materials and Methods: Primary normal adult human endothelial cells and fibroblasts at early passage were used. Upon exposure to pure nicotine, cigarette smoke extract, Snus extract and ethanol, these cells were assessed for DNA synthesis, gene expression profile and cellular morphology. Results: Normal human fibroblasts and endothelial cells have unique gene expression profiles. The effects of treatment with ethanol and nicotine from different sources was more prominent in endothelial cells than fibroblasts. The combination of alterated gene expressions and strongly inhibited DNA synthesis was only detected in cells exposed to smoke extract. In the presence and absence of ethanol, pure nicotine and Snus extract induced abnormalities in the cytoplasm without any significant degree of cell death. With similar doses of nicotine and ethanol, the additional components in smoke extract had a dominant effect. The smoke extract induced vast cellular abnormalities and massive cell death. Conclusion: Cigarette smoke induced massive cell death and various abnormalities at cellular and molecular levels in surviving endothelial cells and fibroblasts. The combination of genomic alterations and the chronic inflammatory microenvironment induced from massive cell death, will potentially promote tumourigenesis and various diseases in cigarette smokers.

  • 43.
    Laytragoon-Lewin, Nongnit
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Chen, Fu
    Castro, Juan
    Elmberger, Göran
    Rutqvist, Lars Erik
    Lewin, Freddi
    Turesson, Ingela
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Lundgren, Jan
    DNA Content and Methylation of p16, DAPK and RASSF1A Gene in Tumour and Distant, Normal Mucosal Tissue of Head and Neck Squamous Cell Carcinoma Patients2010In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 30, no 11, p. 4643-4648Article in journal (Refereed)
    Abstract [en]

    Long-term survival of head and neck squamous cell carcinoma (HNSCC) patients has not improved significantly during the last 20 years and recurrent disease is frequently observed. In this study, the potential presence of pre-malignant cells or rare malignant cells at the time of diagnosis in HNSCC was investigated. Patients and Methods: Fifty-nine biopsies obtained from 41 HNSCC patients were analysed. Eighteen of these biopsies were normal mucosal tissue, located at least 5 cm from the tumour margin. DNA content and DNA methylation of p16, DAPK and RASSF1A was examined. Results: Thirty-nine out of 41 (95%) tumour biopsies showed p16 methylation and 21 (51%) of them displayed aneuploidy. Of 18 distant normal mucosal biopsies, 6 (33%) of these showed evidence of aneuploidy and 15(83%) of them showed methylated p16 genes. Among paired samples, the highest frequencies of DNA methylation were found in tumours with aneuploidy. Regardless of DNA content, methylation at DAPK, RASSF1A or p16 were found in the corresponding distant mucosal biopsies. Conclusion: The cells with abnormal DNA content or DNA methylation in mucosal tissue were not detected clinically or by pathological macroscopic and microscopic examination. Thus, distant mucosal tissue DNA content and DNA methylation analyses in combination with histopathology will provide a better prognostic base for the evaluation and treatment of HNSCC patients.

  • 44.
    Laytragoon-Lewin, Nongnit
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Nilsson, Per J.
    Castro, Juan
    Gharizadeh, Baback
    Nyrén, Pål
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Elmberger, Göran
    Turesson, Ingela
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Oncology.
    Svensson, Christer
    Human papillomavirus (HPV), DNA aberrations and cell cycle progression in anal squamous cell carcinoma patients2007In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 27, no 6C, p. 4473-4479Article in journal (Refereed)
    Abstract [en]

    Human papillomavirus (HPV) infections of the genital tract are sexually transmitted and prevalent worldwide. In this study, the role of HPV in 72 patients with anal squamous cell carcinoma was investigated. Patients and Methods: Polymerase chain reaction (PCR) in combination with in situ hybridization was used to identify HPV-DNA in the patients' biopsies. The HPV typing was conducted by pyrosequencing. Cell cycle and DNA content were analysed by cytometry. Results: Ninety percent of the carcinoma biopsies carried high-risk oncogenic HPV in their malignant cells. Eighty-one percent of these demonstrated a single infection with HPV16, 18 or 33 and 19% were double infected with HPV16 and HPV18. Accumulations of viral genes were seen at the necrotic area of the tumours. The HPV genome in the tumour cell influenced significantly the host cell cycle progression, but not DNA aberrations. Within these patients, HPV status in the malignant cells was not found to be associated with patient survival time. Conclusion: High-risk oncogenic HPV may play an important role in the initiation of host cell proliferation in anal squamous cell carcinoma. However, infection with HPV may not have any direct influence itself on the clinical outcome of these patients considering the treatments currently available.

  • 45.
    Li, Li
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Heldin, Nils-Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Grawé, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Ulmsten, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Fu, Xin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Induction of apoptosis or necrosis in human endometrial cancer cells by 2-Methoxyestradiol2004In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 24, no 6, p. 3983-3990Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    We investigated the effects of 2methoxyestradiol (2-ME), an endogenous estrogenic metabolite, on human endometrial cancer HEC-1-A and RL-95-2 cell lines.

    MATERIALS AND METHODS:

    After exposure of HEC-1-A and RL-95-2 cells to 2-ME, the morphological changes were evaluated by acridine orange staining and transmission electron microscopy. Cell cycle progress, apoptosis and necrosis were assessed by flow cytometry, DNA fragmentation and Western blot.

    RESULTS:

    2-ME inhibited cell growth by blocking the S- and G2/M-phase in both cell lines, by inducing apoptosis in HEC-1-A cells and by causing necrosis in RL-95-2 cells. Apoptosis, on HEC-1-A cells, was accompanied by an increased expression of iNOS and STAT1. This apoptotic effect was prevented by the iNOS inhibitor 1400W and eliminated by the caspase inhibitor Z-VAD-FMK. Necrosis, on RL-95-2 cells, was due to a severe disruption of the mitochondrial membrane potential. 2-ME had no significant effect on normal human endometrial cells.

    CONCLUSION:

    The data suggest that 2-ME has an antitumor effect on human endometrial carcinoma cells (HEC-1-A and RL-95-2) and may contribute as a new therapeutic agent for endometrial cancer patients.

  • 46. Lindahl, B.
    et al.
    Ranstam, J.
    Willén, Roger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Prospective malignancy grading of invasive squamous carcinoma of the uterine cervix. Prognostic significance in a long-term follow-up2007In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 27, no 4C, p. 2829-2832Article in journal (Refereed)
    Abstract [en]

    A multifactorial grading score (MGS) for invasive squamous cell carcinoma of the uterine cervix has demonstrated its capacity to predict survival in a 5-10 year perspective and metastasis frequencies, and is a valuable tool for treatment schedules. In this study it was shown that the power of prognosis is valid even up to 20 years. In this material from 619 cervical carcinoma patients the MGS scores turned out to remain as strong as earlier proven. Earlier studies have shown that MGS is superior to other mono- and multifactorial grading systems, histological differentiation into cell types, age, clinical stage, irradiation and DNA-analysis. Treatment of cervical squamous cell carcinoma is more specific today to meet the patients' need for instance to preserve fertility or to minimize operation and eventually radiotherapy. The MGS score is a strong prognostic tool in patients with cervical carcinoma.

  • 47. Lindahl, Bengt
    et al.
    Andolf, Ellika
    Ingvar, Christian
    Ranstam, Jonas
    Willén, Roger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Adjuvant tamoxifen in breast cancer patients affects the endometrium by time, an effect remaining years after end of treatment and results in an increased frequency of endometrial carcinoma2008In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 28, no 2B, p. 1259-1262Article in journal (Refereed)
    Abstract [en]

    Tamoxifen is the most used adjuvant drug in breast cancer treatment. Its main action is as an anti-oestrogen, but in the endometrium of some patients it acts as an oestrogen. Some investigators have even reported an increased risk of developing endometrial carcinoma. The question of how to follow-up these patients and how to identify patients at risk of developing endometrial premalignant changes was investigated by the noninvasive ultrasound method. The follow-up of 292 patients from before the start of adjuvant treatment with tamoxifen and 94 without tamoxifen treatment was conducted at regular intervals. The changes in endometrial thickness as measured by ultrasound and histopathological changes are reported. A thicker endometrium was found in patients with receptor positive breast cancer even before the treatment with tamoxifen started. Cumulative increasing thickness was found during treatment and this thicker endometrium remained until almost 3 years after the end of treatment. If the endometrium was <3 mm after 3 months of treatment the probability that it would be thin after 5 years was high. An increased risk of developing endometrial carcinoma was found, however due to this regular follow-up the cancer was identified at an early stage.

  • 48. Lindahl, Bengt
    et al.
    Måsbäck, Anna
    Persson, Jan
    Ranstam, Jonas
    Willlén, Roger
    Adenocarcinoma corpus uteri stage I-II: results of a treatment programme based upon cytometry2009In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 29, no 11, p. 4731-4735Article in journal (Refereed)
    Abstract [en]

    The results of a treatment method on adenocarcinoma corpus uteri stage I-II based upon cytometrically measured DNA ploidy are presented. All patients had a simple hysterectomy. Adjuvant treatment (postoperative vaginal brachytherapy) were given only to those patients with non-diploid tumours regardless of stage and grade. A total of 1,634 women with endometroid adenocarcinoma corpus uteri stage I-II were included where 1,396 patients were followed-up for at least 5 years or until death and the remaining 238 patients were followed-up 3.5-5 years or until death. By using cytometry only, we identified a low-risk group comprising 83% of the patients (with 5.2% dead from their disease) and a high-risk group of 17% (with 15.7% dead from their disease). By using grade only (well- and moderately differentiated vs poorly differentiated), the low-risk group comprised 87% of the patients (with 4.6% dead from their disease) and the high-risk group 13% (with 13% dead from their disease). By using stage only (stage Ia and Ib vs stage Ic and II), the low-risk group comprised 78% of the patients (with 3.6% dead from their disease) and the high risk group 22% (with 14.5% dead from their disease). By combining these prognostic parameters, we were able to identify small subgroups with increased mortality rates in need of adjuvant therapy. As ploidy still had a strong prognostic strength regardless of given adjuvant radiotherapy, we do not believe that this treatment was effective. We therefore recommend future research to be directed toward cytostatics as an alternative adjuvant treatment.

  • 49. Lindahl, Bengt
    et al.
    Måsbäck, Anna
    Persson, Jan
    Ranstam, Jonas
    Willén, Roger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Adenocarcinoma Corpus Uteri Stage I-II: Results of a Treatment Programme Based upon Cytometry2009In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 29, no 11, p. 4731-4735Article in journal (Refereed)
    Abstract [en]

    The results of a treatment method on adenocarcinoma corpus uteri stage I-II based upon cytometrically measured DNA ploidy are presented. All patients had a simple hysterectomy. Adjuvant treatment (postoperative vaginal brachytherapy) were given only, to those patients with non-diploid tumours regardless of stage and grade. A total of 1,634 women with endometroid adenocarcinoma corpus uteri stage I-II were included where 1,396 patients were followed-up for at least 5 years or until death and the remaining 238 patients were followed-up 3.5-5 years or until death. By using cytometry only, we identified a low-risk group comprising 83% of the patients (with 52% dead from their disease) and a high-risk group of 17% (with 15.7% dead from their disease). By using grade only (well- and moderately differentiated vs poorly differentiated), the low-risk group comprised 87% of the patients (with 4.6% dead from their disease) and the high-risk group 13% (with 13% dead from their disease). By using stage only (stage Ia and Ib vs stage Ic and II), the low-risk group comprised 78% of the patients (with 3.6% dead from their disease) and the high risk group 22% (with 14.5% dead from their disease). By combining these prognostic parameters, we were able to identify small subgroups with increased mortality rates in need of adjuvant therapy. As ploidy still had a strong prognostic strength regardless of given adjuvant radiotherapy, we do not believe that this treatment was effective. We therefore recommend future research to be directed toward cytostatics as an alternative adjuvant treatment.

  • 50. Lindahl, Bengt
    et al.
    Persson, Jan
    Ranstam, Jonas
    Willén, Roger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Long-term survival in uterine clear cell carcinoma and uterine papillary serous carcinoma2010In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 30, no 9, p. 3727-3730Article in journal (Refereed)
    Abstract [en]

    Uterine clear cell carcinoma (UCC) and uterine papillary serous carcinoma (UPSC) are rare entities that differ in clinical behavior from endometrial adenocarcinoma. Compared with endometrioid adenocarcinoma, they more often metastasize early and more commonly in the upper abdomen including the omentum. Treatment programs of UCC and UPSC at different stages vary and range from no adjuvant therapy in stage Ia to a wide variety of chemotherapies and radiotherapies in more advanced stages. This study presents the outcome of 109 patients with UCC or UPSC treated according to essentially the same treatment program from May 1993 to December 2004. Most patients were treated with a simple hysterectomy with no further adjuvant treatment. In stage Ia, 2/46 patients died of their disease and amongst all the stages, 30/109 patients died of their disease. These survival outcomes are comparable to or better than those presented previously.

12 1 - 50 of 81
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