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- Janelidze, Shorena, et al.
(författare)
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Immunizations With IFN gamma Secreting Tumor Cells can Eliminate Fully Established and Invasive Rat Gliomas
- 2009
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Ingår i: Journal of Immunotherapy. - 1524-9557. ; 32:6, s. 593-601
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Tidskriftsartikel (refereegranskat)abstract
- Immunotherapy of malignant primary brain tumors holds the potential to improve the dismal prognosis after current clinical therapy. Although immunotherapy of experimental gliomas has been demonstrated to have the capacity to cure intracerebral tumors no convincing effects of immunotherapy have been shown in clinical trials. One reason for this could be that some of the models used do not display full features of human glioblastomas. The N29 rat gliomas exhibited all the histologic features of human glioblastoma multiforme including nuclear atypia, mitotic figures, necrosis, and diffuse infiltration into the normal brain tissue. Surprisingly, immunotherapy with autologous interferon gamma producing tumor cells against preestablished intracerebral N29 turners yielded a higher cure rate than immunotherapy against less invasive tumors. Furthermore, when immunizations were postponed until day 5 after tumor establishment 50% of the animals survived. When immunizations were postponed until day 11 after tumor establishment no glioma-bearing animals were cured but survival was significantly prolonged. The superior effect of immunotherapy in the invasive N29 model compared with the less invasive tumors could depend oil combined effects of up-regulation of major histocompatibility complex I and induction of major histocompatibility complex II plus CD80 after transfection and irradiation of the tumor cells used for immunizations. This study demonstrates that immunotherapy against experimental brain tumors indeed is feasible even against highly invasive and established tumors. These results strengthen the translational potential of immunotherapy against malignant brain tumors.
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| 2. |
- Berg, Svante, et al.
(författare)
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Sex life and sexual function in men and women before and after total disc replacement compared with posterior lumbar fusion
- 2009
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Ingår i: The spine journal. - : Elsevier BV. - 1529-9430 .- 1878-1632. ; 9:12, s. 987-994
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Tidskriftsartikel (refereegranskat)abstract
- Background contextSex life and sexual function may be affected by low back pain (LBP). Sexual dysfunction after anterior lumbar fusion is reported in both men and women, but focus is mainly on impaired male biological function (retrograde ejaculation) as this may cause infertility. This has led to concern as to whether anterior surgery should be employed in men, at least in younger age groups.PurposeTo investigate how chronic low back pain (CLBP) of assumed discogenic origin affects sex life and sexual function in patients considered for surgical treatment, whether this is affected by surgical treatment (total disc replacement [TDR] or posterolateral fusion [PLF]/posterior lumbar interbody fusion [PLIF]), and if so, are there differences between the surgical procedures undertaken.Study designA randomized controlled trial comparing TDR and instrumented lumbar spine fusion, performed either as a PLF or PLIF.Patient sampleOne hundred fifty-two patients were included in this randomized controlled trial to compare the effect on CLBP of either TDR via an anterior retroperitoneal approach or instrumented posterior lumbar fusion, PLF or PLIF.Outcome measuresGlobal assessment of back pain, back pain (visual analog scale [VAS] 0-100), function (Oswestry Disability Index [ODI] 0–100), quality of life (EQ5D [EuroQol] 0–1), and answers on specific sexual function.MethodsOutcome was assessed using data from the Swedish Spine Register (SweSpine). In ODI, one question, ODI 8, reflects the impact of back pain on sex life. This question was analyzed separately. Patients also answered a gender-specific questionnaire preoperatively and at the 2-year follow-up to determine any sexual dysfunction regarding erection, orgasm, and ejaculation. Follow-up was at 1 and 2 years.ResultsBefore surgery, 34% reported that their sex life caused some extra LBP, and an additional 30% that their sex life was severely restricted by LBP. After surgery, sex life improved in both groups, with a strong correlation to a reduction of LBP. The gender-specific questionnaire used to measure sexual function after 2 years revealed no negative effect of TDR or Fusion in men regarding erection or retrograde ejaculation. However, 26% of all men in the Fusion group, compared with 3% in the TDR group, reported postoperative deterioration in the ability to achieve orgasm, despite a reduction of LBP.ConclusionsImpairment of sex life appears to be related to CLBP. An improvement in sex life after TDR or lumbar fusion was positively correlated to a reduction in LBP. Total disc replacement in this study, performed through an anterior retroperitoneal approach, was not associated with greater sexual dysfunction compared with instrumented lumbar fusion performed either as a PLF or as a PLIF. Sexual function, expressed as orgasm, deteriorated in men in the Fusion group postoperatively, in spite of this group reporting less LBP after 2 years.
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| 3. |
- Enell Smith, Karin, et al.
(författare)
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Cure of established GL261 mouse gliomas after combined immunotherapy with GM-CSF and IFNgamma is mediated by both CD8(+) and CD4(+) T-cells.
- 2009
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 124:3, s. 630-637
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Tidskriftsartikel (refereegranskat)abstract
- We were the first to demonstrate that combined immunotherapy with GM-CSF producing GL261 cells and recombinant IFNgamma of preestablished GL261 gliomas could cure 90% of immunized mice. To extend these findings and to uncover the underlying mechanisms, the ensuing experiments were undertaken. We hypothesized that immunizations combining both GM-CSF and IFNgamma systemically would increase the number of immature myeloid cells, which then would mature and differentiate into dendritic cells (DCs) and macrophages, thereby augmenting tumor antigen presentation and T-cell activation. Indeed, the combined therapy induced a systemic increase of both immature and mature myeloid cells but also an increase in T regulatory cells (T-regs). Cytotoxic anti-tumor responses, mirrored by an increase in Granzyme B-positive cells as well as IFNgamma-producing T-cells, were augmented after immunizations with GM-CSF and IFNgamma. We also show that the combined therapy induced a long-term memory with rejection of intracerebral (i.c.) rechallenges. Depletion of T-cells showed that both CD4(+) and CD8(+) T-cells were essential for the combined GM-CSF and IFNgamma effect. Finally, when immunizations were delayed until day 5 after tumor inoculation, only mice receiving immunotherapy with both GM-CSF and IFNgamma survived. We conclude that the addition of recombinant IFNgamma to immunizations with GM-CSF producing tumor cells increased the number of activated tumoricidal T-cells, which could eradicate established intracerebral tumors. These results clearly demonstrate that the combination of cytokines in immunotherapy of brain tumors have synergistic effects that have implications for clinical immunotherapy of human malignant brain tumors. (c) 2008 Wiley-Liss, Inc.
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| 5. |
- Strömqvist, Björn, et al.
(författare)
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The Swedish Spine Register : Development, design and utility
- 2009
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Ingår i: European spine journal. - : Springer Science and Business Media LLC. - 0940-6719 .- 1432-0932. ; 18:S 3, s. 294-304
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Tidskriftsartikel (refereegranskat)abstract
- The Swedish Spine Register enables monitoring of surgical activities focusing on changes in trends over time, techniques utilized and outcome, when implemented in general clinical practice. Basic requirements for a prosperous register are unity within the profession, mainly patient-based documentation and a well functioning support system. This presentation focuses on the development and design of the register protocol, problems encountered and solutions found underway. Various examples on how the results can be presented and utilized are given as well as validation. Register data demonstrate significant gender differences in lumbar disc herniation surgery with females having more pain, lower quality of life and more pronounced disability preoperatively while improvement after surgery is similar between genders. Quality of life after surgery for degenerative disorders is significantly improved for disc herniation, stenosis, spondylolisthesis and disc degenerative disorders. Over the last 10 years, surgical treatment for spinal stenosis has increased gradually while disc herniation surgery decreases regarding yearly number of procedures. An added function to the register enables more complex prospective clinical studies to include register data together with data suitable for the individual study. A common core set of demographic, surgical and outcome parameters would enable comparisons of clinical studies within and between nations.
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