| 1. |
- Dictor, Michael, et al.
(författare)
-
Strong lymphoid nuclear expression of SOX11 transcription factor defines lymphoblastic neoplasms, mantle cell lymphoma and Burkitt's lymphoma.
- 2009
-
Ingår i: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 1592-8721 .- 0390-6078. ; 94:11, s. 1563-1568
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We surveyed lymphomas to determine the range of expression of the mantle cell lymphoma-associated SOX11 transcription factor and its relation to cyclin D1. DESIGN AND METHODS: On hundred and seventy-two specimens were immunostained for the SOX11 N and C termini. Cyclin D1 was detected by immunohistochemistry and quantitative reverse transcriptase polymerase chain reaction; in situ hybridization for t(11;14) was applied when needed. RESULTS: Nuclear SOX11 was strongly expressed in most B and T-lymphoblastic leukemia/lymphomas and half of childhood Burkitt's lymphomas, but only weakly expressed in some hairy cell leukemias. Chronic lymphocytic leukemia/lymphoma, marginal zone, follicular and diffuse large B-cell lymphomas were negative for SOX11, as were all cases of intermediate Burkitt's lymphomas/diffuse large B-cell lymphoma, myeloma, Hodgkin's lymphomas and mature T-cell and NK/T-cell lymphomas. CONCLUSIONS: In addition to mantle cell lymphoma, SOX11 is strongly expressed only in lymphoblastic malignancies and Burkitt's lymphomas. Its expression is independent of cyclin D1 (except for weak expression in hairy cell leukemias) and unlikely to be due to translocations in lymphoid neoplasia.
|
|
| 2. |
- Nordström, Lena, et al.
(författare)
-
SOX11 and TP53 add prognostic information to MIPI in a homogenously treated cohort of mantle cell lymphoma : a Nordic Lymphoma Group study
- 2014
-
Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 166:1, s. 98-108
-
Tidskriftsartikel (refereegranskat)abstract
- Mantle cell lymphoma (MCL) is an aggressive B cell lymphoma, where survival has been remarkably improved by use of protocols including high dose cytarabine, rituximab and autologous stem cell transplantation, such as the Nordic MCL2/3 protocols. In 2008, a MCL international prognostic index (MIPI) was created to enable stratification of the clinical diverse MCL patients into three risk groups. So far, use of the MIPI in clinical routine has been limited, as it has been shown that it inadequately separates low and intermediate risk group patients. To improve outcome and minimize treatment-related morbidity, additional parameters need to be evaluated to enable risk-adapted treatment selection. We have investigated the individual prognostic role of the MIPI and molecular markers including SOX11, TP53 (p53), MKI67 (Ki-67) and CCND1 (cyclin D1). Furthermore, we explored the possibility of creating an improved prognostic tool by combining the MIPI with information on molecular markers. SOX11 was shown to significantly add prognostic information to the MIPI, but in multivariate analysis TP53 was the only significant independent molecular marker. Based on these findings, we propose that TP53 and SOX11 should routinely be assessed and that a combined TP53/MIPI score may be used to guide treatment decisions.
|
|
| 3. |
- Sernbo, Sandra
(författare)
-
Functional studies of SOX11 and T-STAR - Translation of tumor-associated genes into clinical and biological insight
- 2013
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cancer is a disease that will affect most of us during a lifetime. Although the survival of cancer patients has incresed due to better treatment and earlier diagnosis, the prevalance of the disease is still increasing. This increase in the number of cancer cases diagnosed will impose a challenge to the cancer care and higher costs for socitey. Personalized medicine aims at reducing these costs while at the same time improving the care for the patient, mainly by using a more individualized therapy, but also a more preventive cancer care and even earlier diagnosis. For example, a more indivivualized treatment can target specific genetic aberrations found in a patient, and avoid treating those patients who lack the aberrations and therefore will not respond. To accomplish the goals of personalized medicine, biomarkers that can divide patients into different subgroups are needed. The aim of this thesis was to explore SOX11 and T-STAR as potential biomarkers in cancer. I was also interested in the function of these proteins in the tumor tissues where they are specifically expressed. Immunohistochemistry on tissue microarrays was used to evaluate the expression of SOX11 and T-STAR in primary tumor tissues, and the expression was then correlated to survival in the patients. The function of the proteins was explored using RNA interference and overexpression experiements in cancer cell lines. The results from my studies are presented in five papers in this thesis. First, we could confirm the diagnostic role of SOX11 in mantle cell lymphoma (MCL). Second, I show the prognostic potential of this protein, as patients with high expression of SOX11 are associated with a better survival, both in MCL and high-grade epithelial ovarian cancer. In MCL, SOX11 could possibly complement the MCL international prognostic index MIPI , a prognostic biomarker already in use in this disease. Third, in both tumor types SOX11 functions as a tumor-suppressor in vitro. Regarding T-STAR, its expression is correlated with better outcome for breast cancer patients, and therefore shows potential as a prognostic biomarker. Our studies also show that T-STAR has a growth-inhibitory function in breast cancer cell lines. In conclusion, both SOX11 and T-STAR are biomarkers that could be used in personalized medicine to subgroup patients and potentially guide treatment decisions. Both proteins function as growth-inhibitors in vitro, which correlates to the better prognosis for the patients with tumors expressing the proteins in vivo.
|
|
| 4. |
- Sernbo, Sandra, et al.
(författare)
-
Nuclear T-STAR Protein Expression Correlates with HER2 Status, Hormone Receptor Negativity and Prolonged Recurrence Free Survival in Primary Breast Cancer and Decreased Cancer Cell Growth In Vitro
- 2013
-
Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:7, s. e70596-
-
Tidskriftsartikel (refereegranskat)abstract
- T-STAR (testis-signal transduction and activation of RNA) is an RNA binding protein, containing an SH3-binding domain and thus potentially playing a role in integration of cell signaling and RNA metabolism. The specific function of T-STAR is unknown and its implication in cancer is poorly characterized. Expression of T-STAR has been reported in human testis, muscle and brain tissues, and is associated with a growth-inhibitory role in immortalized fibroblasts. The aim of this paper was to investigate the functional role of T-STAR through (i) survival analysis of patients with primary invasive breast cancer and (ii) experimental evaluation of the effect of T-STAR on breast cancer cell growth. T-STAR protein expression was analysed by immunohistochemistry (IHC) in tissue microarrays with tumors from 289 patients with primary invasive breast cancer, and correlations to clinicopathological characteristics, recurrence-free and overall survival (RFS and OS) and established tumor markers such as HER2 and ER status were evaluated. In addition, the function of T-STAR was investigated using siRNA-mediated knock-down and overexpression of the gene in six breast cancer cell lines. Of the tumors analysed, 86% showed nuclear T-STAR expression, which was significantly associated with an improved RFS and strongly associated with positive HER2 status and negative hormone receptor status. Furthermore, experimental data showed that overexpression of T-STAR decreased cellular growth while knock-down increased it, as shown both by thymidine incorporation and metabolic activity. In summary, we demonstrate that T-STAR protein expression correlates with an improved RFS in primary breast cancer. This is supported by functional data, indicating that T-STAR regulation is of importance both for breast cancer biology and clinical outcome but future studies are needed to determine a potential role in patient stratification.
|
|
| 5. |
- Sernbo, Sandra, et al.
(författare)
-
The tumour suppressor SOX11 is associated with improved survival among high grade epithelial ovarian cancers and is regulated by reversible promoter methylation
- 2011
-
Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 11
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The neural transcription factor SOX11 has been described as a prognostic marker in epithelial ovarian cancers (EOC), however its role in individual histological subtypes and tumour grade requires further clarification. Furthermore, methylation-dependent silencing of SOX11 has been reported for B cell lymphomas and indicates that epigenetic drugs may be used to re-express this tumour suppressor, but information on SOX11 promoter methylation in EOC is still lacking. Methods: SOX11 expression and clinicopathological data was compared using chi(2) test in a cohort of 154 cases of primary invasive EOC. Kaplan-Meier analysis and the log rank test were applied to evaluate ovarian cancer-specific survival (OCSS) and overall survival (OS) in strata, according to SOX11 expression. Also, the methylation status of the SOX11 promoter was determined by sodium bisulfite sequencing and methylation specific PCR (MSP). Furthermore, the effect of ectopic overexpression of SOX11 on proliferation was studied through [3H]-thymidine incorporation. Results: SOX11 expression was associated with an improved survival of patients with high grade EOC, although not independent of stage. Further analyses of EOC cell lines showed that SOX11 mRNA and protein were expressed in two of five cell lines, correlating with promoter methylation status. Demethylation was successfully performed using 5'-Aza-2'deoxycytidine (5-Aza-dC) resulting in SOX11 mRNA and protein expression in a previously negative EOC cell line. Furthermore, overexpression of SOX11 in EOC cell lines confirmed the growth regulatory role of SOX11. Conclusions: SOX11 is a functionally associated protein in EOC with prognostic value for high-grade tumours. Re-expression of SOX11 in EOC indicates a potential use of epigenetic drugs to affect cellular growth in SOX11-negative tumours.
|
|
