| 1. |
- Andersson, Ann-Catrin, 1968-
(författare)
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Studies on Human Endogenous Retroviruses (HERVs) with Special Focus on ERV3
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Human endogenous retroviruses (HERVs) represent approximately 7% of the human genome. This investigation was focused on one particular HERV, ERV3, with the main purpose of characterising its gene expression patterns and genomic distribution of ERV3-like sequences. Furthermore, this careful expression study should provide insights into the biological role of HERVs. The impact of HERVs in health and disease is not yet clarified. ERV3 is expressed as three envelope (env) transcripts, of which two also contain a cellular gene, H-plk (human proviral linked Krüppel). ERV3 env expression was mainly investigated at the RNA level. The gene expression of two other HERVs, HERV-K and HERV-E was analysed and compared with ERV3 activity.Real-time PCRs were developed and in combination with in situ hybridisation, it was found that ERV3 is expressed in a tissue- and cell-specific way. High levels of ERV3 mRNA (up to six times over Histone3.3) were demonstrated in placenta, sebaceous glands, foetal and adult adrenal glands, brown adipose tissue, corpus luteum, pituitary gland, thymus and testis. In monocytic cells including both normal monocytes and malignant U-937 cells, elevated mRNA levels were observed after retinoic acid (RA)-induced differentiation. ERV3-encoded Env protein was detected in selected cases, one following RA-treatment. In addition, several new ERV3-like sequences were discovered in the human genome. ERV3 was found to have conserved open reading frames in contrast to other ERV3-like sequences in the human genome. This suggests that ERV3 may be involved in important cellular processes such as differentiation, cell fusion, immunomodulation and protection against infectious retroviruses. The developed techniques and obtained results will allow further studies of HERV expression to better correlate HERV activity to both normal development and disease.
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| 2. |
- Antonio, L D, et al.
(författare)
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The non-random location of human oncogenes and tumour suppressor genes
- 2005
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Ingår i: Caryologia. - 0008-7114. ; 58:1, s. 1-14
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Tidskriftsartikel (refereegranskat)abstract
- We have analysed 994 sites for oncogenes and tumour suppressor genes located within human chromosome bands. The data presented disclose that: 1) These cancer genes build ridges as well as hot spots, which are not related to the position of other types of genes present in these chromosomes. 2) The frequency of cancer genes is not directly related to chromosome length, to the number of DNA bases per chromosome or to the number of structural genes present in each chromosome. 3) Suppressor genes tend to occupy the same location as oncogenes. 4) Several cancer genes occur in as many as 15 different sites spread over 10 different chromosomes. 5) The main feature of the distribution of both oncogenes and suppressors, is that they tend to be located near telomeres. Moreover, their numbers decrease from the telomere to the centromere building a distinct gradient. The difference is statistically significant. The present evidence, taken together, indicates that the telomeric territory might be a preferential location of cancer related genes and thereby also of stem cell genes.
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| 3. |
- Badn, Wiaam, et al.
(författare)
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Low-dose combretastatin A4 phosphate enhances the immune response of tumor hosts to experimental colon carcinoma
- 2006
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Ingår i: Clinical Cancer Research. - 1078-0432. ; 12:15, s. 4714-4719
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Although there is a need to enhance the therapeutic efficiency in cancer by combining immunotherapeutic procedures with other therapy, combination with chemotherapy is complicated due to immunosuppressive effects of most chemotherapeutic drugs. The purpose of this investigation was to study whether combining tumor cell immunization with the vascular targeting drug combretastatin A4 phosphate (CA4P) would enhance tumor retardation and/or affect the antitumor immune response. Experimental Design: Rats with intrahepatic colon carcinoma were immunized weekly with IL-18/IFN gamma-transfected tumor cells, starting day 9, and were treated with a low-dose CA4P (2 mg/kg, 5 days a week starting day 7). The effect of CA4P was studied on tumor growth and on immune reactivity in vitro. Results: Rats with preexisting tumor, immunized and treated with low-dose CA4P, had a significantly retarded tumor growth compared with rats receiving CA4P or immunization alone. Splenocytes from rats treated with this combination had a significantly enhanced antitumor immune response compared with splenocytes from control rats. Exposure of nonadherent splenocytes to CA4P in vitro did not enhance their proliferation. However, 3-hour pretreatment of adherent splenocytes with 0.3 mu g/mL CA4P significantly enhanced proliferation and IFN gamma production of admixed nonadherent splenocytes, partly due to nitric oxide reduction. Combining the nitric oxide synthase inhibitor N-nitro-L-arginine methyl ester with CA4P and immunization further retarded tumor growth. Conclusion: Concomitant treatment of rats with progressively growing tumor with immunization and low-dose CA4P significantly enhances the therapeutic effect as compared with either treatment alone and results in an enhanced antitumor immune reactivity.
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| 4. |
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| 5. |
- Carlsson, Anders, et al.
(författare)
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Plasma proteome profiling reveals biomarker patterns associated with prognosis and therapy selection in glioblastoma multiforme patients
- 2010
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Ingår i: Proteomics Clinical Applications. - : Wiley. - 1862-8354 .- 1862-8346. ; 4:6-7, s. 591-602
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Glioblastoma multiforme (GBM) is a frequent and aggressive type of primary brain tumor with a heterogeneous origin. GBM is highly therapy resistant and carries a dismal prognosis for the patient. The purpose of this discovery study was to define candidate plasma biomarker signatures for improved classification and novel means for selecting patients for refined individualized therapy. Experimental design: Here, we have for the first time investigated the applicability of large-scale recombinant antibody-based microarrays, targeting mainly immunoregulatory analytes, for sensitive and selective plasma protein profiling of GBM patients undergoing immunotherapy with autologous IFN-gamma transfected glioma cells Results: This proof-of-concept study showed that candidate plasma protein signatures associated with GBM were outlined that could be used for GBM classification, monitoring the effects of the immunotherapy as well as for stratifying patients according to the beneficial effect of the adopted immunotherapy Further, central key cytokines that could be utilized for optimization and/or refinement of the immunotherapeutic regime were indicated. Conclusions and clinical relevance: Candidate plasma proteins signatures associated with GBM was outlined, that could be used for GBM classification and for pre-operatively stratifying patients according to the beneficial effect of the adopted immunotherapy.
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| 6. |
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| 7. |
- Fan, Xiaolong, et al.
(författare)
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Glioma stem cells: Evidence and limitation.
- 2007
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Ingår i: Seminars in Cancer Biology. - : Elsevier BV. - 1096-3650 .- 1044-579X. ; 17:3, s. 214-218
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Forskningsöversikt (refereegranskat)abstract
- Gliomas, in particular the high-grade anaplastic glioma and glioblastoma multiforme (GBM), are manifested by morphological, genetic and phenotypic heterogeneity. Most of the studies hitherto have been performed on bulk glioma cells, with limited understanding on the origin and the relative contribution of particular glioma cell populations to glioma growth and progression. Recent studies have demonstrated the existence of a small fraction of glioma cells endowed with features of primitive neural progenitor cells and tumor-initiating function. Such cells have been defined as glioma stem cells. However, questions remain as to whether the currently identified glioma stem cells are the cell-of-origin for glioma initiation and progression, or the results of such processes. In this review, we discuss the current evidence and limitation in identifying glioma stem cells and the potential origin of glioma stem cells in the context of post-natal neural cell regeneration and their transformation mechanisms. The implication of these findings for glioma diagnosis and treatment will also be reviewed.
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| 8. |
- Gullberg, Urban, et al.
(författare)
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The cytotoxic eosinophil cationic protein (ECP) has ribonuclease activity
- 1986
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Ingår i: Biochemical and Biophysical Research Communications. ; 139:3, s. 1239-1242
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Tidskriftsartikel (refereegranskat)abstract
- The eosinophil cationic protein (ECP) is a specific cytotoxic constituent of granules. In this work we demonstrated that ECP has a ribonuclease activity. Purified ECP was resolved by ion exchange chromatography into subfractions, which all showed ribonuclease activity. Another eosinophil granule protein, EPX, identical with eosinophil-derived neurotoxin (EDN) had a 125-fold higher RNase activity than ECP. ECP may exert its cytotoxic effects on parasites and cells because of its extreme basicity alone or it may be internalized and act by degrading mRNA.
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| 9. |
- Johansson, Anna C, et al.
(författare)
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Enhanced expression of iNOS intratumorally and at the immunization site after immunization with IFNgamma-secreting rat glioma cells
- 2002
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Ingår i: Journal of Neuroimmunology. - 1872-8421. ; 123:1-2, s. 135-143
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Tidskriftsartikel (refereegranskat)abstract
- Nitric oxide (NO) can modulate both tumor growth and antitumor immune responses. In order to elucidate the mechanism of curative therapeutic immunization with IFNgamma-producing glioma cells, we examined the expression of inducible nitric oxide synthase (iNOS) in tissue sections from immunized animals. There was a significantly enhanced iNOS expression both intratumorally and at the immunization site. Although the mechanisms behind this dual expression of iNOS most probably are different, our results suggest a role for NO in both the induction and execution of the antitumor response.
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| 10. |
- Järås, Marcus, et al.
(författare)
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Human short-term repopulating cells have enhanced telomerase reverse transcriptase expression.
- 2006
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 108:3, s. 1084-1091
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Tidskriftsartikel (refereegranskat)abstract
- Telomerase activity has been suggested to be critically involved in hematopoietic stem cell (HSC) self-renewal. However, it has been unclear whether human HSCs have telomerase activity and how telomerase activity is regulated within the HSC and progenitor pool. Here, we isolated living cord-blood (CB) CD34+ cells with up-regulated human telomerase reverse transcriptase (hTERT) expression by using an hTERT-reporting adenoviral vector encoding destabilized green fluorescent protein (dGFP) driven by the hTERT promoter, and functionally characterized them in comparison with control vector–transduced CD34+ cells expressing GFP. Following a 2-day serum-free transduction protocol, cells were sorted into a dGFP+ and a GFP+ fraction. Cell-cycle analysis revealed that the dGFP+ cells had a greater proportion of cells in S/G2/M phase compared with the GFP+ cells, (56% ± 1.8% vs 35% ± 4.3%; P < .001) and fewer cells in G0 phase (8.1% ± 3.0% vs 20% ± 4.7%; P < .01) However, the colony-forming and short-term nonobese diabetic/severe combined immunodeficient (NOD/SCID) B2m–/– mice bone marrow–repopulating capacities were similar between the dGFP+ and the GFP+ cells. Interestingly, the dGFP+ cells had a 6-fold lower repopulating capacity in NOD/SCID mice compared with the GFP+ cells and lacked secondary NOD/SCID B2m–/– mice bone marrow–repopulating capacity. Thus, up-regulation of hTERT expression within the CB HSC pool is accompanied by decreased self-renewal capacity.
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