| 11. |
- Elgbratt, Kristina, 1969, et al.
(author)
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Aberrant T-cell ontogeny and defective thymocyte and colonic T-cell chemotactic migration in colitis-prone Galphai2-deficient mice
- 2007
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In: Immunology. - : Wiley. - 0019-2805 .- 1365-2567. ; 122:2, s. 199-209
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Journal article (peer-reviewed)abstract
- Galphai2-deficient mice, which spontaneously develop colitis, have previously been reported to have an increased frequency of mature, single positive thymocytes compared to wild-type mice. In this study we further characterized the intrathymic changes in these mice before and during overt colitis. Even before the onset of colitis, Galphai2(-/-) thymi weighed less and contained fewer thymocytes, and this was exacerbated with colitis development. Whereas precolitic Galphai2(-/-) mice had unchanged thymocyte density compared to Galphai2(+/-) mice of the same age, this was significantly decreased in mice with colitis. Thymic atrophy in Galphai2(-/-) mice involved mainly the cortex. Using a five-stage phenotypic characterization of thymocyte maturation based on expression of CD4, CD8, TCRalphabeta, CD69 and CD62L, we found that both precolitic and colitic Galphai2(-/-) mice had significantly increased frequencies of mature single-positive CD4(+) and CD8(+) medullary thymocytes, and significantly reduced frequencies and total numbers of immature CD4(+) CD8(+) double-positive thymocytes compared to Galphai2(+/-) mice. Furthermore, cortical and transitional precolitic Galphai2(-/-) thymocytes showed significantly reduced chemotactic migration towards CXCL12, and a trend towards reduced migration to CCL25, compared to wild-type thymocytes, a feature even more pronounced in colitic mice. This impaired chemotactic migration of Galphai2(-/-) thymocytes could not be reversed by increased chemokine concentrations. Galphai2(-/-) thymocytes also showed reduced expression of the CCL25 receptor CCR9, but not CXCR4, the receptor, for CXCL12. Finally, wild-type colonic lamina propria lymphocytes migrated in response to CXCL12, but not CCL25 and, as with thymocytes, the chemokine responsiveness was significantly reduced in Galphai2(-/-) mucosal lymphocytes.
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| 12. |
- Fredin, Maria Fritsch, 1970, et al.
(author)
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The application and relevance of ex vivo culture systems for assessment of IBD treatment in murine models of colitis
- 2008
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In: Pharmacological Research. - : Elsevier BV. - 1043-6618 .- 1096-1186. ; 58:3-4, s. 222-231
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Journal article (peer-reviewed)abstract
- The aim of this study was to investigate the relevance of mouse ex vivo cultures as a first screening model for new therapeutic agents of Inflammatory Bowel Disease (IBD). Two murine models (dextran sodium sulphate (DSS)-induced colitis and Gαi2-deficient mice) and two anti-inflammatory agents (methyl-prednisolone and the proteasome inhibitor MG132) were evaluated. The in vivo effects of methyl-prednisolone were assessed in both models. Ex vivo colonic tissue from both mouse models were cultured in the presence or absence of the drugs and TaqMan Low-Density arrays were used to assess the regulation of inflammatory genes before and after drug treatment. Colitis induced a similar inflammatory gene profile in both mouse models in in vivo studies and in ex vivo cultures. The differences encountered reflected the different phases of colitis in the models, e.g. innate cytokine/chemokine profile in the DSS model and T cell related markers in Gαi2-deficient mice. After steroid treatment, a similar pattern of genes was suppressed in the two mouse models. We confirmed the suppression of inflammatory gene expression for IL-1β, IL-6 and iNOS in ex vivo and in vivo colons from both mouse models by quantitative RT-PCR. Importantly, the inflammatory responses in the murine ex vivo culture system reflected the in vivo response in the inflamed colonic tissue as assessed by changes in inflammatory gene expression, suggesting that the murine culture system can be used for validation of future IBD therapies.
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| 13. |
- Friberg, Britt, et al.
(author)
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Endometrial destruction by thermal coagulation : Evaluation of a new form of treatment for menorrhagia
- 1998
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In: Gynaecological Endoscopy. - : Wiley. - 0962-1091 .- 1365-2508. ; 7:2, s. 73-78
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Journal article (peer-reviewed)abstract
- Objective. To report the first clinical evaluation of a new balloon endometrial, thermal destruction system Cavaterm®, for outpatient treatment of menorrhagia. Design. To elucidate possible technical problems during treatment, to evaluate how the patients tolerated the treatment and to judge which patients were suitable for this form of treatment. Main outcome measures. Measurements of bleeding volumes in pads and tampons before and after treatment were performed as well as subjective evaluation by bleeding charts. Patients also estimated their degree of satisfaction. Setting. Gynaecology department at a university hospital. Subjects. 36 patients under 52 pears of age with menorrhagia, without suspicion of intracavitary pathology including malignancy. Results. No procedure-related complications occurred. The patients tolerated the treatment well. There was a significant reduction in measured bleeding volumes in pads and tampons, collected during one menstruation, 2-7 months after treatment compared with measurements before treatment. Four patients subsequently underwent hysterectomy and should not have been included in the study (two with pedunculated myoma and one with a septum; the fourth showed premalignant endometrial changes in the curettage preceding the treatment). At 18-28-month follow up, 29 of the suitable patients (91%) reported a significant reduction in bleeding and another three patients reported reduced but still profuse bleeding compared with pretreatment; 88% (28/32) rated the treatment results as excellent, and a further 9% (3/32) as good. Conclusions. We found the Cavaterm® system for endometrial destruction to be safe, efficient and easy to use.
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| 14. |
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| 15. |
- Holgersson, Georg, et al.
(author)
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The prognostic value of pre-treatment thrombocytosis in two cohorts of patients with non-small cell lung cancer treated with curatively intended chemoradiotherapy
- 2017
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In: Neoplasma (Bratislava). - Bratislava : AEPress. - 0028-2685 .- 1338-4317. ; 64:6, s. 909-915
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Journal article (peer-reviewed)abstract
- Chemoradiotherapy is the standard of care for inoperable stage III non-small cell lung cancer (NSCLC). This treatment, however, offers only a small chance of cure and is associated with many side effects. Little research has been made concerning which patients benefit most/least from the treatment. The present study evaluates the prognostic value of anemia, leukocytosis and thrombocytosis at diagnosis in this treatment setting. In the present study, data were collected retrospectively for 222 patients from two different phase II studies conducted between 2002-2007 in Sweden with patients treated with chemoradiotherapy for stage IIIA-IIIB NSCLC. Clinical data and the serum values of hemoglobin (Hgb), White blood cells (WBC) and Platelets (Plt) at enrollment were collected for all patients and studied in relation to overall survival using Kaplan-Meier product-limit estimates and a multivariate Cox proportional hazards regression model. The results showed that patients with thrombocytosis (Plt > 350 x 109 /L) had a shorter median overall survival (14.5 months) than patients with normal Plt at baseline (23.7 months). Patients with leukocytosis (WBC > 9 x 109 /L) had a shorter median survival (14.9 months) than patients with a normal WBC at baseline (22.5 months). However, in a multivariate model including all lab parameters and clinical factors, only thrombocytosis and performance status displayed a prognostic significance. In Conclusion, thrombocytosis showed to be an independent prognostic marker associated with shorter overall survival in stage III NSCLC treated with curatively intended chemoradiotherapy. This knowledge can potentially be used together with established prognostic factors, such as performance status when choosing the optimal therapy for the individual patient in this clinical setting
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| 16. |
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| 17. |
- Lindahl, Bengt, et al.
(author)
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Adenocarcinoma Corpus Uteri Stage I-II : Results of a Treatment Programme Based upon Cytometry
- 2009
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In: Anticancer Research. - 0250-7005 .- 1791-7530. ; 29:11, s. 4731-4735
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Journal article (peer-reviewed)abstract
- 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.
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| 18. |
- Lindahl, Bengt, et al.
(author)
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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 carcinoma
- 2008
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In: Anticancer Research. - 0250-7005 .- 1791-7530. ; 28:2B, s. 1259-1262
-
Journal article (peer-reviewed)abstract
- 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.
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| 19. |
- Lindahl, Bengt, et al.
(author)
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Long-term survival in uterine clear cell carcinoma and uterine papillary serous carcinoma
- 2010
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In: Anticancer Research. - 0250-7005 .- 1791-7530. ; 30:9, s. 3727-3730
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Journal article (peer-reviewed)abstract
- 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.
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| 20. |
- Lindahl, Bengt, et al.
(author)
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Relapse of Endometrial Carcinoma : Follow-up of 272 Patients with Relapse
- 2012
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In: Anticancer Research. - 0250-7005 .- 1791-7530. ; 32:8, s. 3391-3395
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Journal article (peer-reviewed)abstract
- A total of 2090 patients with endometrial carcinoma were followed-up for at least five years. The treatment modalities, as well as the results of treatment, regarding 272 patients with disease relapse are presented. The results are not encouraging. We found no statistically significant difference regarding overall survival, when the patients were divided according to initial stage or ploidy status. There was also no significant difference between overall survival and the mode of treatment. 108 out of 272 patients with relapse died of their disease. Regarding patients in stage I-II we present the survival for every studied year, where we compared those with more than one site of metastasis (n=108), more than one metastasis (n=59), or no relapse at all (n=1289) with an age-corrected Swedish female population. We found that the vast majority of patients did not die from their cancer-related illnesses, and also found an increased death-rate among those with cancer without relapse, compared to those without cancer (20% compared to 14%, 5 year follow-up). We conclude that the majority of patients would benefit from an increased effort to cure other illnesses rather than concentrating on cancer treatment alone.
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