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  • 56351.
    Öberg, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine.
    On the role of the myc proto-oncogene and cytokines in the control of monocytic differentiation1992Doctoral thesis, comprehensive summary (Other academic)
  • 56352.
    Öberg, Fredrik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Haseeb, Adil
    Ahnfelt, Matilda
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Pontén, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Westermark, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    El-Obeid, Adila
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Herbal melanin activates TLR4/NF-kappaB signaling pathway2009In: Phytomedicine, ISSN 0944-7113, E-ISSN 1618-095X, Vol. 16, no 5, p. 477-84Article in journal (Refereed)
    Abstract [en]

    Expression of many pro-inflammatory cytokines is controlled by the NF-kappaB signaling pathway. NF-kappaB is induced by LPS through activation of TLR4. Melanins extracted from fungal, plant and human sources modulate cytokine production and activate NF-kappaB pathway. We showed that a herbal melanin (HM) from Nigella sativa L. modulates cytokine production and suggested it as a ligand for TLR4. In this study we investigated the possibility that the HM-induced cytokine production is via an NF-kappaB signaling pathway. We found that HM induced the degradation of IkappaBalpha, a key step in the activation of NF-kappaB. Moreover, addition of IkappaB kinase (IKK) specific inhibitors effectively inhibited the observed HM-induced production of IL-8 and IL-6 by TLR4-transfected HEK293 cells and THP-1 cells. Our results have also shown that HM induced cleavage of caspase 8, and that this cleavage was partially abrogated by IKK inhibitors. We suggest that HM can modulate the inflammatory response by inducing IL-8 and IL-6 production via TLR4-dependent activation of the NF-kappaB signaling pathway.

  • 56353.
    Öberg, Fredrik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Nilsson, Kenneth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Monocytes and Macrophages1996In: Transplantation Biology: Cellular and molecular aspects / [ed] Nicholas L. Tilney, Terry B. Strom, Leendert C. Paul, Philadelphia: Lippincott-Raven , 1996, p. 241-Chapter in book (Other academic)
  • 56354.
    Öberg, Fredrik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Wu, S.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Bahram, Fuad
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Nilsson, Kenneth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Larsson, L.G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Cytokine-induced restoration of differentiation and cell cycle arrest in v-Myc transformed U-937 monoblasts correlates with reduced Myc activity2001In: Leukemia, ISSN 0887-6924, E-ISSN 1476-5551, Vol. 15, no 2, p. 217-227Article in journal (Refereed)
    Abstract [en]

    Deregulated expression of the myc-family of oncogenes in hematopoietic and other cell types plays an important role in tumorigenesis, and results in increased proliferative potential and block of cellular differentiation. We have previously shown that IFN-gamma restores phorbol ester-induced differentiation and cell cycle arrest in v-myc transformed human U-937 monoblasts. To investigate whether other cytokine signals could also abrogate such a block, IL-1, IL-3, IL-4, IL-6, IL-7, IL-10, IL-11, LIF, oncostatin M, M-CSF, G-CSF and GM-CSF, and TGFbeta1, TNF-alpha, IFN-alpha were examined. We show that GM-CSF and IL-6, in combination with the phorbol ester 12-O-tetradecanoyl-phorbol acetate (TPA), restored differentiation and cell cycle arrest. In contrast, treatment by TGFbeta1 +/- TPA resulted in an efficient G1/G0 arrest, but did not appear to induce terminal differentiation. Restoration of differentiation and cell cycle arrest was accomplished despite maintained expression of the v-Myc protein. Our results show that the cytokine-induced signals reduced Myc-dependent transcription of an artificial target promoter/reporter gene construct, correlating in most, but not all, cases with decreased association of v- and c-Myc with its essential partner, Max. Thus, cytokine-induced signals may counteract the activity of deregulated Myc, and contribute to the normalization of differentiation, arrest in the G1/G0 phase of the cell cycle, or both.

  • 56355.
    Öberg, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine.
    Neutrophil granule proteins in cells and serum: studies during pregnancy and in patients with diabetes and leukemia1986Doctoral thesis, comprehensive summary (Other academic)
  • 56356.
    Öberg, K
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Eriksson, Barbro
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Digestive endocrine tumor management; Medical advanced disease1999Chapter in book (Other scientific)
  • 56357.
    Öberg, K
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Jakobsson, Å
    Gustavsson, G
    Wilander, E
    Lundqvist, G
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Stridsberg, M
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    WDHA syndrome caused by a ganglioneuroblastoma producing vasoactive intestinal polypeptide and neuropeptide Y1986In: Scand. J. Gastroenterol, Vol. 21, no suppl 119, p. 228-229Article in journal (Refereed)
  • 56358.
    Öberg, K
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Stridsberg, M
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Neuroendocrine tumors2002In: Tumor markers: physiology, pathobiology, technology and clinical applications, 2002, p. 339-349Chapter in book (Other scientific)
  • 56359.
    Öberg, Katarina
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
    On Conditions of Swedish Women’s Sexual Well-Being: An Epidemiological Approach2005Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Objectives: This descriptive epidemiological dissertation aims to identify conditions of Swedish women’s sexual well-being. The focus is on the relationship between their idiosyncratically reported levels, during the last 12 months, of 5 sexual functions/dysfunctions per se and distressing and their socio-psychological situation, including aspects of their sexual history. Levels of sexual functions/dysfunctions are also related to levels of sexual satisfaction and to other aspects of life satisfaction.

    Methods: Data on a randomized cross-sectional national sample of 1335 women aged 18-74 (59% of target sample) were gathered in 1996 using a combination of structured interviews and questionnaires/checklists. Analyses were performed for the total sample or for sub-samples aged 18-65 years. In 3 of the 4 dissertational articles, trichotomies of a 6-grade scale characterizing level of sexual dysfunctions into No/Mild/Manifest dysfunction were used.

    Main results: Mild sexual dysfunctions were, generally, much more common than were manifest, and dysfunctional distress was considerably less common than were dysfunctions per se. All dysfunctions, and in particular orgasmic dysfunction, were closely associated with level of sexual well-being. Four factors independently pair-wise linking levels of dysfunctions per se with levels of distressful dysfunction were identified. These were Sexual interest/Desire, Genital function (lubrication and dyspareunia), Orgasm, Vaginismus. Three of these (not vaginismus) were powerful classificators of gross level of sexual well-being. Many of socio-demographic and socio-psychological contextual life-conditions were significantly associated with the different sexual functions/dysfunctions. However, the most prominent contextual variables were satisfaction with partner relationship and partner’s levels of sexual functions.

    In conclusion, many different socio-psychological aspects must be taken into account to optimize treatment modalities and resources when dealing with women’s sexual dysfunction in order to secure a good level of sexual well-being.

    List of papers
    1. On sexual well-being in sexually abused Swedish women: epidemiological aspects.
    Open this publication in new window or tab >>On sexual well-being in sexually abused Swedish women: epidemiological aspects.
    2002 In: Sexual and Relationship Therapy, ISSN 1468-1994, Vol. 17, no 4, p. 329-341Article in journal (Refereed) Published
    Identifiers
    urn:nbn:se:uu:diva-93192 (URN)
    Available from: 2005-05-18 Created: 2005-05-18Bibliographically approved
    2. On categorization and quantification of women's sexual dysfunctions: An epidemiological approach.
    Open this publication in new window or tab >>On categorization and quantification of women's sexual dysfunctions: An epidemiological approach.
    2004 In: International Journal of Impotence Research, ISSN 0955-9930, Vol. 16, p. 261-269Article in journal (Refereed) Published
    Identifiers
    urn:nbn:se:uu:diva-93193 (URN)
    Available from: 2005-05-18 Created: 2005-05-18Bibliographically approved
    3. On Swedish women's distressing sexual dysfunctions: Some concomitant conditions and life satisfaction.
    Open this publication in new window or tab >>On Swedish women's distressing sexual dysfunctions: Some concomitant conditions and life satisfaction.
    2005 In: Journal of Sexual Medicine, Vol. 2, p. 160-180Article in journal (Refereed) Published
    Identifiers
    urn:nbn:se:uu:diva-93194 (URN)
    Available from: 2005-05-18 Created: 2005-05-18Bibliographically approved
    4. On orgasm, sexual behavior and erotic perceptions in 18-74 year-old Swedish women.
    Open this publication in new window or tab >>On orgasm, sexual behavior and erotic perceptions in 18-74 year-old Swedish women.
    Show others...
    Manuscript (Other academic)
    Identifiers
    urn:nbn:se:uu:diva-93195 (URN)
    Available from: 2005-05-18 Created: 2005-05-18 Last updated: 2010-01-13Bibliographically approved
  • 56360.
    Öberg, Katarina
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
    Fugl-Meyer, Axel
    Fugl-Meyer, Kerstin
    On categorization and quantification of women's sexual dysfunctions: An epidemiological approach.2004In: International Journal of Impotence Research, ISSN 0955-9930, Vol. 16, p. 261-269Article in journal (Refereed)
  • 56361.
    Öberg, Katarina
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
    Fugl-Meyer, Axel
    Fugl-Meyer, Kerstin
    On categorization and quantification of women's sexual dysfunctions:: An epidemiological approach2004In: International Journal of Impotence Research, ISSN 0955-9930, Vol. 16, no 3, p. 261-269Article in journal (Refereed)
  • 56362.
    Öberg, Katarina
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
    Fugl-Meyer, Kerstin
    Fugl-Meyer, Axel
    On sexual well-being in sexually abused Swedish women: epidemiological aspects.2002In: Sexual and Relationship Therapy, ISSN 1468-1994, Vol. 17, no 4, p. 329-341Article in journal (Refereed)
  • 56363.
    Öberg, Katarina
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
    Fugl-Meyer, Kerstin
    Fugl-Meyer, Axel
    On sexual well-being in sexually abused Swedish women: epidemiological aspects2002In: Sexual and Relationship Therapy, ISSN 1468-1994, Vol. 17, no 4, p. 329-341Article in journal (Refereed)
  • 56364.
    Öberg, Katarina
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. rehabiliteringsmedicin.
    Fugl-Meyer, Kerstin S
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. rehabiliteringsmedicin.
    On categorization and quantification of women's sexual dysfunctions: An epidemiological approach2004In: International Journal of Impotence Research, Vol. 16, p. 261-269Article in journal (Refereed)
  • 56365.
    Öberg, Katarina
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. Rehabiliteringsmedicin.
    Fugl-Meyer, Kerstin S
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience. Rehabiliteringsmedicin.
    On Swedish Women´s Distressing Sexual Dysfunctions:Some Concomitant Conditions and Life Satisfaction2005In: J Sex Med, Vol. 2, p. 169-180Article in journal (Refereed)
  • 56366.
    Öberg, Katarina
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
    Fugl-Meyer, Kerstin S
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
    Fugl-Meyer, Axel R
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
    On sexual well-being in sexually abused Swedish women:epidemiological aspects.2002In: Sexual and RelationshipTherapy, Vol. 4, p. 329-Article in journal (Refereed)
  • 56367.
    Öberg, Katarina
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
    Sjögren Fugl-Meyer, Kerstin
    On Swedish women's distressing sexual dysfunctions: Some concomitant conditions and life satisfaction.2005In: Journal of Sexual Medicine, Vol. 2, p. 160-180Article in journal (Refereed)
  • 56368.
    Öberg, Katarina
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
    Sjögren Fugl-Meyer, Kerstin
    On Swedish women's distressing sexual dysfunctions:: Some concomitant conditions and life satisfaction2005In: Journal of Sexual Medicine, ISSN 1743-6109, Vol. 2, no 2, p. 169-180Article in journal (Refereed)
  • 56369.
    Öberg, Kjell
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    A perspective on the treatment of gastro-entero pancreatic tumors (GEP). Octreotide: The Next Decade1999Chapter in book (Other scientific)
  • 56370.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Advances in Neuroendocrine Tumor Management2011Collection (editor) (Refereed)
  • 56371.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Biotherapies for GEP-NETs2012In: Baillière's Best Practice & Research: Clinical Gastroenterology, ISSN 1521-6918, E-ISSN 1532-1916, Vol. 26, no 6, p. 833-841Article in journal (Refereed)
    Abstract [en]

    Biological treatment for GI neuroendocrine tumours (NETs) includes treatment with somatostatin analogues and alpha interferons. Both of these therapies were developed in the early 1980's and initially for treatment of a carcinoid syndrome in patients with small intestinal NETs. Later on tumour biology studies indicated that well differentiated NETs (G1-tumours) benefit from treatment with somatostatin analogues and alpha interferons. Both agents give symptomatic improvement in patients with functioning tumours in 40-60% of the patients, biochemical responses in 50-70% of the patients and significant tumour shrinkage in 5-10% of the patients. Combination therapy with somatostatin analogues and alpha interferon has demonstrated some clinical benefit. In conclusion: Somatostatin analogues and alpha interferons are still playing an important role and considered to be first-line treatment in functioning and in non-functioning well-differentiated NETs, (G1-tumours) and somatostatin analogues might also be applied to control clinical symptoms in G2-tumours with higher proliferation.

  • 56372.
    Öberg, Kjell
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. Onkologisk endokrinologi.
    Business Briefing: European oncology review2005In: Business Briefing: European oncology reviewArticle in journal (Refereed)
  • 56373.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Cancer: antitumor effects of octreotide LAR, a somatostatin analog2010In: Nature reviews. Endocrinology, ISSN 1759-5029, Vol. 6, no 4, p. 188-189Article in journal (Refereed)
    Abstract [en]

    Treatment of nonfunctioning neuroendocrine tumors with somatostatin analogs has been controversial, given the low antitumor effects of these drugs. The ProMid study group now reports that octreotide lar (long-acting release) has a substantial antitumor effect, with longer progression-free survival compared with placebo in patients with well-differentiated neuroendocrine tumors and low tumor burden.

  • 56374.
    Öberg, Kjell
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Carcinoid and flushing syndromes2001Chapter in book (Other scientific)
  • 56375.
    Öberg, Kjell
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Carcinoid syndrom1997In: Clinical Endocrine Oncology, Sheaves, Jenkins, Wass, Blackwell Scientific Publications Ltd , 1997Chapter in book (Other scientific)
  • 56376.
    Öberg, Kjell
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. Endokrin onkologi.
    Carcinoid tumors - current considerations2007In: A Century of Advances in Neuroendocrine tumor biology and treatment, Felsenstein , 2007, p. 40-53Chapter in book (Refereed)
  • 56377.
    Öberg, Kjell
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. Onkologisk endokrinologi.
    Carcinoid tumors, carcinoid syndrome and related disorders2002In: Williams Textbook of Endocrinology. 10th edition, Saunders , 2002, p. 1857-1876Chapter in book (Refereed)
  • 56378.
    Öberg, Kjell
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. Endokrin onkologi.
    Carcinoid tumors, carcinoid syndrome and related disorders2007In: Williams Textbook of Endocrinology. 11th edition, Saunders Elsevier , 2007, p. 1821-1840Chapter in book (Refereed)
  • 56379.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Circulating biomarkers in gastroenteropancreatic neuroendocrine tumours2011In: Endocrine-Related Cancer, ISSN 1351-0088, E-ISSN 1479-6821, Vol. 18 Suppl 1, p. S17-S25Article in journal (Refereed)
  • 56380.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Clinical management of neuroendocrine GEP-tumors - Current concepts and future directions2007In: Medicinska Istrazivanja: The Journal of the School of Medicine University of Belgrade, ISSN 0301-0619, Vol. 41, no 1, p. 24-27Article in journal (Refereed)
  • 56381.
    Öberg, Kjell
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. Onkologisk endokrinologi.
    Diagnostic Pathways2006In: Neuroendocrine Tumors Handbook: Chaper 5 - Diagnostic Pathways, BioScientifica , 2006Chapter in book (Refereed)
  • 56382.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Diagnostic work-up of gastroenteropancreatic neuroendocrine tumors2012In: Clinics, ISSN 1807-5932, E-ISSN 1980-5322, Vol. 67, no S 1, p. 109-112Article, review/survey (Refereed)
    Abstract [en]

    Neuroendocrine tumors are a heterogeneous group of malignancies that present a diagnostic challenge. The majority of patients (more than 60%) present with metastatic disease at diagnosis. The diagnosis is based on histopathology, imaging, and circulating biomarkers. The histopathology should contain specific neuroendocrine markers such as chromogranin A, synaptophysin, and neuron-specific enolase and also an estimate of the proliferation by Ki-67 (MIB-1). Standard imaging procedures consist of computed tomography or magnetic resonance imaging together with somatostatin receptor scintigraphy. 68Ga-DOTA-octreotate scans will in the future replace somatostatin receptor scintigraphy because they have higher specificity and sensitivity. Other positron imaging tomographic scanning tracers that will come into clinical use are 18F-DOPA and 11C-5HTP. Neuroendocrine tumors secrete many different peptides and amines that can be used as circulating biomarkers. The most useful general marker is chromogranin A, which is both a diagnostic and prognostic marker in most neuroendocrine tumors. However, there is still a need for improved biomarkers for early detection and follow-up of patients during treatment. In addition, molecular imaging can be further developed for both detection and evaluation of treatment.

  • 56383.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Gallium-68 somatostatin receptor PET/CT: Is it time to replace (111)Indium DTPA octreotide for patients with neuroendocrine tumors?2012In: Endocrine (Basingstoke), ISSN 1355-008X, E-ISSN 1559-0100, Vol. 42, no 1, p. 3-4Article in journal (Other academic)
  • 56384.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Genetics and molecular pathology of neuroendocrine gastrointestinal and pancreatic tumors (gastroenteropancreatic neuroendocrine tumors)2009In: Current Opinion in Endocrinology, Diabetes and Obesity, ISSN 1752-296x, Vol. 16, no 1, p. 72-78Article in journal (Refereed)
    Abstract [en]

    PURPOSE OF REVIEW: Gastrointestinal and pancreatic neuroendocrine tumors (GEP-NETs) originate from cells of the diffuse endocrine system. Most GEP-NETs are sporadic, however, some of them, especially pancreatic endocrine tumors, may occur as part of familial syndromes. The genetic and molecular pathology of neuroendocrine tumor development is incomplete and remains largely unknown. However, the WHO classification introduced in clinical practice will give more insight into genetic and molecular changes related to tumor subtypes.RECENT FINDINGS: In sporadic endocrine pancreatic tumors, losses of chromosome 1 and 11q as well as gain on 9q appear to be early invents in development of pancreatic tumors because they are already present in small tumors. Multiple genetic defects may accumulate with time and result in pancreatic neuroendocrine tumor progression and malignancy. Gastrointestinal endocrine tumors (carcinoids) show predominantly genetic alterations concentrated on chromosome 18. There are losses of the entire chromosome as well as smaller deletions. The most frequently reported mutated gene in gastrointestinal neuroendocrine tumors is b-catenin. Overexpression of cyclin D1 and cMyc has also been reported. Recently, a set of genes NAP1L1, MAGE-2D and MTA1 has been correlated with malignant behavior of small intestinal carcinoids. SUMMARY: Molecular profiling of GEP-NETs demonstrates that pancreatic endocrine tumors and gastrointestinal neuroendocrine tumors (carcinoids) display different genetic changes and should, therefore, be considered to be different tumor entities; thereby, also differently managed clinically. Although the number of genetic changes is higher in malignant tumors, we are still far away from defining a malignant profile in GEP-NETs.

  • 56385.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    How does PROMID change the treatment landscape of NET2010Other (Refereed)
  • 56386.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Implications for clinical practice and trial design2012In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 23, no 9, p. 47-48Article in journal (Other academic)
  • 56387.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Interferon: Does it still play a role?2007Conference paper (Refereed)
  • 56388.
    Öberg, Kjell
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Interferon in gastrointestinal tumors - Carcinoid tumors.1995Chapter in book (Other scientific)
  • 56389.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Management of Advanced Small Intestinal Neuroendocrine Tumors2011In: European journal of clinical & medical oncology, ISSN 1759-8966, Vol. 3, no 1, p. 64-70Article in journal (Refereed)
    Abstract [en]

    Small intestinal neuroendocrine tumors (carcinoids) are the most common neuroendocrine tumor (NET) within the gastrointestinal tract (15–20%). The incidence and prevalence is steadily increasing during the last decade and the estimated incidence is now about 2.5/100 000/year. The majority of the tumors produce peptides and amines giving rise to clinical symptoms related to the hormone production such as the carcinoid syndrome with flushing, diarrhea, bronchial constriction, and carcinoid heart disease. The majority of patients present with metastatic disease (60%) and therefore a surgical cure is not obtainable. The medical treatment consists of somatostatin analogs, alpha interferons, and targeted treatment with mTOR- and tyrosine kinase-inhibitors. Somatostatin analogs are still the gold standard for treatment of carcinoid tumors with hormone-related clinical symptoms. A possible antitumor effect has been debated, but a recent study (PROMID) has demonstrated an antitumor effect of octreotide LAR, 30 mg, every 4 weeks versus placebo. Tyrosine kinase inhibitors have been applied mostly for antiangiogenic purposes with objective responses in 10–20% of the patients and PFS of 10–15 months. The mTOR-inhibitor everolimus have demonstrated an antitumor effect in patients with carcinoid tumors in the RADIANT-2 trial. Cytotoxic treatment has demonstrated a limited efficacy in classical low proliferation well-differentiated neuroendocrine gastrointestinal tumors and should not be considered first-line treatment. The future treatment will be based on tumor biology and molecular genetics taking into account the new classification systems. The treatment will be personalized.

  • 56390.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Management of functional neuroendocrine tumors of the pancreas2018In: Gland surgery, ISSN 2227-684X, E-ISSN 2227-8575, Vol. 7, no 1, p. 20-27Article, review/survey (Refereed)
    Abstract [en]

    Pancreatic neuroendocrine tumors (pNETs) constitute a heterogenous group of malignancies with varying clinical presentation, tumor biology and prognosis. The incidence of pNETs has steadily increased during the last decades with an estimated incidence 2012 of 4.8/100,000. Recent whole genome sequencing of pNETs has demonstrated mutations in the DNA repair genes MUTYH and point mutations and gene fusions in four main pathways from chromatin remodeling, DNA damage repair, activation of mechanistic target of rapamycin (mTOR) signaling and the telomere maintenance. This new information will be the foundation for new therapies in the near future for malignant pNETs. The functioning pNETs constitute about 30-40% of all pNETs displaying nine different clinical syndromes: insulinoma, Zollinger-Ellison, Verner-Morrison, glucagonoma, somatostatinomas, ectopic adrenocorticotropic hormone (ACTH) and parathyroid hormone related peptide (PTH-rP) syndromes. Single patients might also present carcinoid syndrome. The diagnostic work-up include histopathology with the new WHO 2017 Classification, biomarkers (CgA, NSE), radiology and molecular imaging including CT-scan, magnetic resonance imaging (MRI), ultrasound and PET-scan. A cornerstone in the treatment of pNETs is surgery which is rarely curative but can reduce the clinical symptoms by debulking which also include radiofrequency ablation, embolization of liver metastases. Medical treatment includes chemotherapy and the targeted agents such as everolimus, sunitinib and peptide receptor radiotherapy (PRRT). Somatostatin analogs has for the last decades been the main stay for management for clinical symptoms related to functioning pNETs and is often combined with new targeted agents as well as chemotherapy. Long-term management of functioning pNETs need a combination of different procedures, surgery, local ablation, targeted agents and somatostatin analogs. Future therapies might be based on the recent advances in molecular genetics and tumor biology.

  • 56391.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Management of metastatic neuroendocrine tumors: Recent advances, Changing trends in the management of NET2010In: NET Journal Club, Vol. 1, no 2Article in journal (Refereed)
  • 56392.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Management of neuroendocrine tumors: Current and future therapies2011In: Expert Reviews Endocrinology & Metabolism, ISSN 1744-6651, Vol. 6, no 1, p. 49-62Article in journal (Refereed)
    Abstract [en]

    Neuroendocrine tumors (NETs) are a genetically diverse group of malignancies that sometimes produce peptides that cause characteristic hormonal syndromes. NETs can be clinically symptomatic (functioning) or silent (nonfunctioning); both types frequently synthesize more than one peptide, although often these are not associated with specific syndromes. Based on data from various sources, the incidence and prevalence of NETs is increasing. The primary treatment goal for patients with NETs is curative, with symptom control and the limitation of tumor progression as secondary goals. Surgery is the only possible curative approach and so represents the traditional first-line therapy. However, as most patients with NETs are diagnosed once metastases have occurred, curative surgery is generally not possible. Patients therefore require chronic postoperative medical management with the aim of relieving symptoms and, in recent years, suppressing tumor growth and spread. Somatostatin analogues, such as octreotide long-acting repeatable (LAR), can improve the symptoms of carcinoid syndrome and stabilize tumor growth in many patients. Results from the placebo-controlled, double-blind, prospective randomized study on the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors (PROMID study) demonstrate that octreotide LAR 30 mg is an effective antiproliferative treatment in patients with newly diagnosed, functionally active or inactive, well-differentiated metastatic midgut NETs. An antiproliferative effect can also be achieved with everolimus, and combination therapy with octreotide LAR has shown synergistic antiproliferative activity. Sunitinib, a tyrosine kinase inhibitor, is active in pancreatic NETs. In the future, pasireotide, the multireceptor targeted somatostatin analogue, has the potential to be an effective therapy for de novo or octreotide-refractory carcinoid syndrome and for inhibiting tumor cell proliferation. Peptide receptor radiotherapy with 90Yttrium-DOTATOC or 177Lutetium-DOTATE is also a new interesting treatment option for NETs.

  • 56393.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Medical Therapy of Gastrointestinal Neuroendocrine Tumors2017In: Visceral Medicine, ISSN 2297-4725, Vol. 33, no 5, p. 352-356Article, review/survey (Refereed)
    Abstract [en]

    Intestinal neuroendocrine tumors (NETs) constitute a heterogeneous group with duodenal, small intestinal, colonic and rectal NETs. They constitute more than half of all NETs, with the highest frequencies in the rectum, small intestine, and colon. The tumor biology varies with the location of the primary tumor as well as with the grade and staging of the tumor. Small intestinal NETs usually present low proliferation and are treated in the first line with somatostatin analogs according to current guidelines. If progression occurs, one can add interferon alpha or change the treatment to everolimus. Peptide receptor radionuclide therapy (PRRT) with Lutetium177-DOTATATE can be an option in the future after registration of the compound. Rectal tumors are usually small when they metastasize; they can be treated with somatostatin analogs but more so with PRRT, while another option is of course everolimus. Colonic NETs are more aggressive than the rest of intestinal NETs and will be treated with everolimus, sometimes in combination with somatostatin analogs based on positive scintigraphy. Another option is a cytotoxic agent such as streptozotocin plus 5-fluorouracil (5-FU) or temozolomide plus capecitabine. The most aggressive tumors, i.e. neuroendocrine carcinoma G3, are treated with a platin-based therapy plus etoposide; if they present with a lower proliferation, i.e. <50%, temozolomide plus capecitabine plus bevacizumab can also be attempted. Duodenal NETs are mostly treated similar to pancreatic NETs, either with cytotoxic agents, streptozotocin plus 5-FU, or temozolomide plus capecitabine, or with targeted agents such as everolimus.

  • 56394.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Molecular Imaging Radiotherapy: Theranostics for Personalized Patient Management of Neuroendocrine Tumors (NETs)2012In: Theranostics, ISSN 1838-7640, Vol. 2, no 5, p. 448-458Article, review/survey (Refereed)
    Abstract [en]

    Neuroendocrine tumors (NETs) possess unique features including expression of peptide hormone receptors as well as the capacity to concentrate and take up precursor forms of amines and peptides making hormones that are stored in secretory granules within the tumor cells (APUD). The expression of somatostatin receptors on tumor cells have been widely explored during the last two decades starting with In-111-DTPA-Octreotide as an imaging agent followed by Ga-68-DOTATOC/TATE positron emission tomography scanning. The new generation of treatment includes (90)Yttrium-DOTATOC/DOTATATE as well as (177)Lutetium-DOTATOC/DOTATATE/DOTANOC treatment of various subtypes of NETs. The objective response rate by these types of PRRT is in the range of 30-45% objective responses with 5-10% grade 3/4 toxicity mainly hematologic and renal toxicity. The APUD mechanism is another unique feature of NETs which have generated an interest over the last two decades to develop specific tracers including C-11-5HTP, F-18-DOPA and C-11-hydroxyefedrin. These radioactive tracers have been developed in centres with specific interest in NETs and are not available everywhere. In-111-DTPA-Octreotide is still the working horse in diagnosis and staging of metastatic NETs, but will in the future be replaced by Ga-68-DOTATOC/DOTATATE PET/CT scanning which provide higher sensitivity and specificity and is also more convenient for the patient because it is a one-stop-procedure. Both (90)Yttrium-DOTATOC/DOTATATE as well as (177)Lutetium-DOTATOC/DOTATATE are important new therapies for malignant metastatic NETs. However, the precise role in the treatment algorithm has to be determined in forthcoming randomized trials.

  • 56395.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine oncology.
    Neuroendocrine gastro-enteropancreatic tumors - from eminence based to evidence-based medicine - A Scandinavian view2015In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 50, no 6, p. 727-739Article, review/survey (Refereed)
    Abstract [en]

    Neuroendocrine tumors (NETs) comprise a heterogenous group of neoplasms with variable clinical expression and progression. The primary tumors most frequently occur in the lungs, intestine and the pancreas. The NET incidence is approximately 6.1/100,000 per year with a prevalence higher than 35/100,000 per year. A NET may be functioning with symptoms related to hormone overproduction or non-functioning, not presenting any hormone-related symptoms. From the early 1980s and onwards, Uppsala University Hospital has contributed significantly to diagnosis, just to mention immunohistochemistry, radio-immunoassays for hormones and peptides and molecular imaging. On the therapeutic side, treatments with cytotoxics as well as biologicals such as, somatostatin analogs and interferons have been evaluated. We have furthermore been involved in important phase III trials for registration of so called, new targeted agents such as, RADIANT-3 and RADIANT-2. Our group were also the first to localize the gene for MEN I on chromosome 11 locus q13. Most recent developments have been the establishments of new biomarkers such as, olfactory receptor E51E1 as well as micro-RNAs in carcinoid tumors of the intestine and lung. A new oncolytic virus, Ad-Vince, for treatment of most NETs has been developed and is ready for the clinic. Furthermore, we have been involved in establishing Nordic and international collaborations. Today, NETs is an area with rapid development and recognized by international organizations at conferences, with large attendance. The Nordic countries continue to be significant contributors to the field.

  • 56396.
    Öberg, Kjell
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Neuroendocrine gastrointestinal tumours - a condensed overview1999In: Annals of Oncology (suppl 2), Vol. 10, p. 3-Article in journal (Refereed)
  • 56397.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Neuroendocrine tumors A growing cancer field2011In: Revista Portuguesa de Cirurgia, ISSN 1646-6918, no 16, p. 23-24Article in journal (Other academic)
  • 56398.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Neuroendocrine tumors (NETs): historical overview and epidemiology2010In: Tumori (Milano), ISSN 0300-8916, E-ISSN 2038-2529, Vol. 96, no 5, p. 797-801Article in journal (Refereed)
    Abstract [en]

    Neuroendocrine tumors (NETs) are a heterogeneous group of neoplasms which take origin from the neuroendocrine cell system and are characterized by embryological, biological and histopathological differences. Traditionally considered as a rare and "niche" pathology, over the last decades they have gained significant attention from the scientific community, even because of their increasing incidence and prevalence probably imputable to the availability of more sensitive diagnostic tools and to the development of higher awareness among clinicians. This paper retraces the key events that led to the discovery, characterization and classification of NETs as well as to the development of adequate treatment strategies. Incidence and epidemiology are also addressed.

  • 56399.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Neuroendocrine tumors of the digestive tract: impact of new classifications and new agents on therapeutic approaches2012In: Current Opinion in Oncology, ISSN 1040-8746, E-ISSN 1531-703XArticle, review/survey (Refereed)
    Abstract [en]

    PURPOSE OF REVIEW:

    Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) constitute a diverse group of neoplasms arising from the diffuse neuroendocrine cell system. During the last 2 years a new classification system, the WHO 2010, has come into clinical practice together with Tumor Nodes Metastases (TNM) staging and grading systems, developed by the European Neuroendocrine Tumor Society/American Joint Cancer Committee. At the same time new targeted agents have been developed for treatment of GEP-NETs and it is important discuss these new agents in relation to the classification and staging system.

    RECENT FINDINGS:

    The current article is reviewing the most important clinical trials of targeting agents within the field of neuroendocrine tumors. Tyrosine kinase inhibitors as well as PI3 kinase mTOR inhibitors have been applied in the treatment of neuroendocrine tumors.

    SUMMARY:

    Sunitinib and everolimus have recently been registered for treatment of pancreatic neuroendocrine tumors worldwide. The role of these new targeted agents in the treatment algorithm of neuroendocrine tumors will be discussed. A large number of phase I and phase II trials have been performed in GEP-NETs with rather limited results and no significant impact on the clinical management of patients with GEP-NETs. However, there are two phase III trials that have completely changed the treatment landscape for pancreatic neuroendocrine tumors, e.g., sunitinib and everolimus demonstrating an increased progression free survival of 11 vs. 5 months for the placebo group.

  • 56400.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Neuroendocrine tumors: recent progress in diagnosis and treatment2011In: Endocrine-Related Cancer, ISSN 1351-0088, E-ISSN 1479-6821, Vol. 18, p. E3-E6Article in journal (Refereed)
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