| 1. |
- Fei, Ying, et al.
(författare)
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The combination of a tumor necrosis factor inhibitor and antibiotic alleviates staphylococcal arthritis and sepsis in mice.
- 2011
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Ingår i: The Journal of infectious diseases. - : Oxford University Press (OUP). - 1537-6613 .- 0022-1899. ; 204:3, s. 348-57
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Tidskriftsartikel (refereegranskat)abstract
- (See the editorial commentary by Chow, on pages 332-4) Background.Despite advances in medical practices, in recent decades permanent reductions in joint function have not been achieved, and the high mortality rate of patients with staphylococcal septic arthritis has not substantially improved. Methods.We evaluated the effects of a combined tumor necrosis factor (TNF) inhibitor and antibiotic therapy on the course of Staphylococcus aureus arthritis and sepsis in mice. Results.Treatment with the combination of a TNF inhibitor and an antibiotic resulted in a quicker relief of clinical arthritis in mice with septic arthritis, compared with an antibiotic monotherapy. Both histopathologically verified synovitis and the extent of joint destruction were reduced by this combined treatment. Importantly, anti-TNF treatment significantly improved the survival rate of mice with S. aureus sepsis and staphylococcal enterotoxin shock syndrome; this effect might be the result of a partial restoration of the hemostatic balance between coagulation and fibrinolysis. Finally, we demonstrated that anti-TNF treatment downregulates high-mobility group protein B1 in staphylococcal enterotoxin shock syndrome. Conclusions.Thus, simultaneous systemic TNF inhibition and antibiotic therapy has beneficial effects on the outcome of S. aureus arthritis and sepsis in a mouse model, suggesting that the combination of a TNF inhibitor and antibiotics represents a novel therapeutic strategy for the treatment of staphylococcal infections.
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| 2. |
- Gustavsson, Helene, 1977, et al.
(författare)
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ADAMTS1, a putative anti-angiogenic factor, is decreased in human prostate cancer.
- 2009
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Ingår i: BJU international. - 1464-410X .- 1464-4096. ; 104:11, s. 1786-90
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To investigate the expression of 'ADAM metallopeptidase with thrombospondin type I motif, 1' (ADAMTS1) in human prostate cancer, and to study its relationship to microvessel density (MVD) and metastasis. ADAMTS1 has been described as an anti-angiogenic and antitumour factor, but its function in prostate cancer is unknown. PATIENTS AND METHODS: ADAMTS1 expression was evaluated by immunohistochemistry in specimens obtained by transurethral resection of the prostate from patients with hormone-naïve and hormone-refractory prostate tumours, including adjacent benign tissue. A semiquantitative scoring system was used for evaluating the staining. MVD was quantified by counting the number of CD34-positive blood vessels. RESULTS: ADAMTS1 was strongly expressed in the luminal epithelial cells in benign prostate glands, whereas expression was significantly lower in prostate cancer cells. There was no obvious difference between hormone-naïve and hormone-refractory tumours, and ADAMTS1 expression did not correlate with Gleason score. However, in hormone-refractory tumours from patients with metastatic disease, the expression of ADAMTS1 was significantly lower than in tumours from patients without metastases. Furthermore, the MVD was higher in hormone-refractory than in hormone-naïve tumours and benign tissue, and MVD correlated with Gleason score. There was no association between ADAMTS1 and MVD in the hormone-naïve tumours, while hormone-refractory tumours with low ADAMTS1 expression had a higher MVD than those with moderate/high expression. CONCLUSION: ADAMTS1 expression is decreased in prostate cancer, and might be involved in the early steps of prostate cancer development. Further, ADAMTS1 might have an anti-angiogenic and antimetastatic role in hormone-refractory prostate cancer, where low ADAMTS1 expression is associated with a high MVD and metastasis.
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| 3. |
- Jennbacken, Karin, 1978, et al.
(författare)
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Expression of vascular endothelial growth factor C (VEGF-C) and VEGF receptor-3 in human prostate cancer is associated with regional lymph node metastasis.
- 2005
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Ingår i: Prostate. - : Wiley. ; 65:2, s. 110-116
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Vascular endothelial growth factor C (VEGF-C) and its receptor, VEGFR-3, have been implicated as important factors in the formation of lymphatic vessels and recent evidence suggests that tumor lymphangiogenesis promotes lymphatic metastasis. METHODS The expression of VEGF-C and VEGFR-3 was examined in 22 human prostate cancer specimens with immunohistochemistry. A semi-quantitative scoring system was used for evaluation of staining. RESULTS Expression of VEGF-C was stronger in prostate cancer areas in comparison to adjacent benign glands. In addition, patients with lymph node metastases had a significantly higher expression of VEGF-C than patients without lymph node metastases. Interestingly, VEGFR-3 was expressed in malignant prostate epithelial cells and its expression was significantly higher in the lymph node positive group compared to the lymph node negative group. CONCLUSIONS The results of the present study indicate that increased expression of VEGF-C and VEGFR-3 play a role in prostate cancer progression and in metastasis to regional lymph nodes. © 2005 Wiley-Liss, Inc.
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| 4. |
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| 5. |
- Khatami, Ali, 1975, et al.
(författare)
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Ki-67 in screen-detected, low-grade, low-stage prostate cancer, relation to prostate-specific antigen doubling time, Gleason score and prostate-specific antigen relapse after radical prostatectomy.
- 2009
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Ingår i: Scandinavian Journal of Urology and Nephrology. - 0036-5599. ; 43:1, s. 12-18
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To evaluate the correlation of Ki-67 as a proliferation marker to prostate-specific antigen doubling time (PSADT), Gleason score and its possible role as a predictor of PSA relapse after radical prostatectomy in early prostate cancer (PC). Material and methods. Out of 660 patients detected with PC in the Swedish branch of the European Randomized Study of Prostate Cancer, 270 were managed with active surveillance. During follow-up (mean 63 months), 70 men were treated with radical retropubic prostatectomy (RRP). In 50 of these patients the preoperative PSADT was calculated and archive prostatectomy specimens were stained for Ki-67. The quantification of positive staining cells was performed by counting five to 15 randomly selected microscopic fields using an eyepiece graticule at 400xmagnification and at least 1000 tumour cells were counted for each patient. One pathologist, blinded to the PSADT values, performed the pathological assessment. The correlation between Ki-67, PSADT and Gleason grade was explored. Cox proportional hazard model was used to evaluate the prognostic power for Ki-67 and other markers on the risk of PSA relapse after RRP. Results. Ki-67 was not correlated with PSADT (p=0.45) but was correlated with Gleason grade (p<0.0001). In the Cox proportional hazard model Ki-67 (p=0.03) [hazard ratio (HR) 2.49, 95% confidence interval (CI) 1.07-5.80] and total PSA (p=0.0068) (HR 1.86, 95% 1.19-2.92) were associated significantly with the risk of disease progression. Conclusion. In men with screen-detected, clinically low-grade, low-stage prostate cancer, Ki-67 may be a valuable prognostic marker of PSA relapse after radical prostatectomy.
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| 6. |
- Kłak, Marcin, et al.
(författare)
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Tranexamic acid, an inhibitor of plasminogen activation, aggravates staphylococcal septic arthritis and sepsis.
- 2010
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Ingår i: Scandinavian journal of infectious diseases. - : Informa UK Limited. - 1651-1980 .- 0036-5548. ; 42:5, s. 351-358
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Haemostatic balance shifts towards pro-coagulation during infection. Plasminogen, a key molecule of fibrinolysis, may play an important role in the pathogenesis of staphylococcal infections. In the present study, we assessed the impact of inhibition of plasminogen activation by tranexamic acid on the course of staphylococcal sepsis and septic arthritis in mice. We found significantly down-regulated plasmin activity and increased D-dimer levels in the blood from the mice with staphylococcal sepsis. Treatment with tranexamic acid significantly increased the severity and mortality of staphylococcal infection. In addition, tranexamic acid reduced the survival rate in a murine model for staphylococcal enterotoxin A-induced death. The aggravation of diseases by tranexamic acid was due neither to the pro-inflammatory cytokine network, nor to impairment of bacterial clearance. Modulation of fibrinolysis, either by supplement of fibrinolytic molecules (tissue plasminogen activator or plasmin) or by fibrinogen depletion, did not reduce the mortality of staphylococcal sepsis. In conclusion, we report that treatment with tranexamic acid led to distinct aggravation of staphylococcal septic arthritis and sepsis in mice, suggesting the clinical importance of fibrinolytic balance in staphylococcal infection.
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| 7. |
- Nordin, Anna, 1977, et al.
(författare)
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Midkine is associated with neuroendocrine differentiation in castration-resistant prostate cancer.
- 2013
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Ingår i: The Prostate. - : Wiley. - 1097-0045 .- 0270-4137. ; 73:6, s. 657-667
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Castration-resistant prostate cancer (CRPC) is an incurable disease and both androgen-deprivation therapy (ADT) and neuroendocrine differentiation (NED) are closely related to CRPC transition. More knowledge concerning neuroendocrine (NE)-transformed PC cells, the NED process and its association with CRPC, is needed. Expression of growth factor midkine (MDK) is correlated with poor clinical outcomes in various human cancers, including PC. In the present study, we have evaluated MDK expression and NED in two separate tumor groups: early and advanced PC. METHODS: Immunohistochemical analysis of MDK, the neuronal marker tubulin-beta III (TUBB3) and the NE-marker chromogranin A (CGA) in a human archival material consisting of hormone naive (HN)/stage T1b (n=29) and CRPC (n=24) tumors. Triple immunofluorescent imaging was performed on a selection of specimens. RESULTS: MDK, TUBB3, and CGA were upregulated in CRPC compared to HN tumors. MDK was highly associated to the expression of both CGA and TUBB3, and identified MDK-positive NE-like looking cells found to co-express CGA or, more commonly, CGA together with TUBB3. CGA and TUBB3 staining displayed a partial expression overlap, an overlap almost exclusively displaying also MDK expression. CONCLUSIONS: MDK upregulation in CRPC is associated with NED (shown by its relation to CGA and TUBB3). The results suggest that MDK represents an over-bridging marker between different populations of NE-like tumor cells, possibly as part of the NED process and associated CRPC transition, something that needs to be evaluated experimentally as does the applicability of MDK as a future target. Prostate © 2012 Wiley Periodicals, Inc.
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| 8. |
- Rask, Katarina, 1966, et al.
(författare)
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Ovarian epithelial cancer: a role for PGE2-synthesis and signalling in malignant transformation and progression
- 2006
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Ingår i: Mol Cancer. - : Springer Science and Business Media LLC. ; 15:5
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Tidskriftsartikel (refereegranskat)abstract
- Background The involvement of the cyclooxygenases (COX), in particular COX-2, is well documented for many tumours, e.g. colon, breast and prostate cancer, by both experimental and clinical studies. There are epidemiological data from subjects using NSAIDs, and experimental evidence supporting the hypothesis of prostaglandins (PGs) as regulators of tumourigenesis in the ovary. One of the end products of PG-synthesis, PGE2, regulates several key-processes, which are characteristic for tumour growth, e.g. angiogenesis, proliferation and apoptosisis. The present study investigated the pathway for PGE2 – synthesis and signalling in ovarian tumourigenesis by analysing specimen from normal ovaries (n = 18), benign (B) (n = 8), borderline type (BL) (n = 6) and malignant tumours (AC) (n = 22). The expression and cell-specific localization of COX-1, COX-2, microsomal prostaglandin E synthase-1 (mPGES-1) and two of the receptors for PGE2, EP1 and EP2, were examined by immunoblotting (IB) and immunohistochemistry (IHC). Results The results are in line with earlier studies demonstrating an increase of COX-2 in AC compared to the normal ovary, B and BL tumours. Increased expressions were also observed for COX-1, mPGES-1 and EP-1 which all were significantly (p < 0.05) augmented in less differentiated AC (grades: moderately-, poorly- and undifferentiated). The increase of COX-2 was also correlated to stage (FIGO classification) with significant elevations in stages II and III. EP1 was increased in stage III while no significant alterations were demonstrated for COX-1, mPGES-1 or EP2 for stage. IHC revealed staining of the tumour cells, but also increase of COX-1, COX-2, mPGES-1 and EP1–2 in the stromal compartment of AC (grades: moderately-, poorly- and undifferentiated). This observation suggests interactions between tumour cells and stromal cells (fibroblasts, immune cells), e.g. paracrine signalling mediated by growth factors, cytokines and possibly PGs. Conclusion The increases of COX-1, COX-2, mPGES-1 and EP1–2 in epithelial ovarian cancer, supports the hypothesis that PGE2-synthesis and signalling are of importance for malignant transformation and progression. The observed augmentations of COX-1, COX-2 and mPGES-1 have implications for future therapeutic strategies.
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| 9. |
- Tomic, Tajana Tesan, et al.
(författare)
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Castration resistant prostate cancer is associated with increased blood vessel stabilization and elevated levels of VEGF and Ang-2.
- 2012
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Ingår i: The Prostate. - : Wiley. - 1097-0045 .- 0270-4137. ; 72:7, s. 705-12
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Tidskriftsartikel (refereegranskat)abstract
- Angiogenesis is important for the progression of prostate cancer and may be a target for treatment in castration resistant (CR) disease. This study was performed to investigate blood vessel stabilization and expression of the pro-angiogenic factors vascular endothelial growth factor (VEGF) and Angiopoietin-2 (Ang-2) in CR and hormone naïve (HN) prostate cancer. The effect of androgen deprivation therapy (ADT) on these parameters was also studied.
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| 10. |
- Vallbo, Christina, 1964, et al.
(författare)
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The expression of thrombospondin-1 in benign prostatic hyperplasia and prostatic intraepithelial neoplasia is decreased in prostate cancer.
- 2004
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Ingår i: BJU Int. - : Wiley. ; 93:9, s. 1339-1343
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE To evaluate the immunohistochemical expression of thrombospondin (TSP), a potent inhibitor of angiogenesis, in human benign prostatic hyperplasia (BPH) and prostate cancer. MATERIALS AND METHODS The expression of TSP-1, TSP-2 and CD36 receptor was assessed in 73 tissue specimens using immunohistochemistry; specimens were from 32 patients with BPH, seven with prostatic intraepithelial neoplasia (PIN) and 34 with cancer. RESULTS Immunohistochemistry showed that all 39 patients with BPH and PIN had TSP-1-positive glands. In contrast, none of the 34 patients with cancer had positive TSP-1 staining in the cancer tissue. All 73 patients were positive for TSP receptor CD36 and negative for TSP-2. CONCLUSIONS TSP is expressed in BPH, down-regulated in PIN and absent in prostate cancer tissue. This may indicate that TSP is important in prostate cancer progression. Further studies are needed to understand the significance of these findings for the malignant transformation of the prostate gland.
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