| 1. |
- Berg, Malin, 1976, et al.
(författare)
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Replacement of a Tracheal Stenosis with a Tissue-Engineered Human Trachea Using Autologous Stem Cells: A Case Report
- 2014
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Ingår i: Tissue Engineering. Part A. - 1937-3341 .- 1937-335X. ; 20:1-2, s. 389-397
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Tidskriftsartikel (refereegranskat)abstract
- Cell-based therapies, involving tissue engineering represent interesting and potentially important strategies for treatment of patients with various disorders. Here, using a detergent-enzymatic method we prepared an intact 3-dimensional scaffold of an extracellular matrix (ECM) derived from a human cadaver donor trachea, which we repopulated with autologous stem cells and implanted into a 76-year old patient with tracheal stenosis including lower part of the larynx. Although the graft provided the patient with an open airway, a week after surgery, the mucous membrane of the graft was covered by a 1-2mm thick fungal infection, which was treated with local and systemic anti-fungal therapy. The airway lumen was postoperatively controlled by fiberbrandoscopy and found stable and sufficient. However, twenty-three days later the patient died due to cardiac arrest but with a patent, open, stable tracheal transplant and intact anastomoses. Histopathological results of the transplanted tracheal graft at autopsy showed a squamous but not ciliated epithelium, neovascularization, bundles of -sma positive muscle cells, serous glands and nerve fibres with S-100 positive nerve cells in the submucosa and intact chondrocytes in the cartilage. Our findings suggest that although autologous stem cells- engineered tracheal matrices may represent a tool for clinical tracheal replacement. Further preclinical studies are required for generating functional airway grafts and long term effects of such grafts.
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| 2. |
- Parris, Toshima Z, 1978, et al.
(författare)
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Additive effect of the AZGP1, PIP, S100A8, and UBE2C molecular biomarkers improves outcome prediction in breast carcinoma
- 2014
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 134:7
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Tidskriftsartikel (refereegranskat)abstract
- The deregulation of key cellular pathways is fundamental for the survival and expansion of neoplastic cells, which in turn can have a detrimental effect on patient outcome. To develop effective individualized cancer therapies, we need to have a better understanding of which cellular pathways are perturbed in a genetically defined subgroup of patients. Here, we validate the prognostic value of a 13-marker signature in independent gene expression microarray datasets (n = 1,141) and immunohistochemistry with full-faced FFPE samples (n = 71). The predictive performance of individual markers and panels containing multiple markers was assessed using Cox regression analysis. In the external gene expression dataset, six of the 13 genes (AZGP1, NME5, S100A8, SCUBE2, STC2, and UBE2C) retained their prognostic potential and were significantly associated with disease-free survival (P < 0.001). Protein analyses refined the signature to a four-marker panel (AZGP1, PIP, S100A8, and UBE2C) significantly correlated with cycling, high grade tumors and lower disease-specific survival rates. AZGP1 and PIP were found in significantly lower levels in invasive breast tissue compared with adjacent normal tissue, whereas elevated levels of S100A8 and UBE2C were observed. A predictive model containing the four-marker panel in conjunction with established clinical variables outperformed a model containing the clinical variables alone. Our findings suggest that deregulated AZGP1, PIP, S100A8, and UBE2C are critical for the aggressive breast cancer phenotype, which may be useful as novel therapeutic targets for drug development to complement established clinical variables. © 2013 Wiley Periodicals, Inc.
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| 3. |
- Fehr, Andre, et al.
(författare)
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The MYB-NFIB gene fusion-a novel genetic link between adenoid cystic carcinoma and dermal cylindroma
- 2011
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Ingår i: The Journal of Pathology. - : Wiley. - 1096-9896 .- 0022-3417. ; 224:3, s. 322-7
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Tidskriftsartikel (refereegranskat)abstract
- We have recently shown that the recurrent t(6;9)(q22 approximately 23;p23 approximately 24) translocation in adenoid cystic carcinoma (ACC) of the breast and head and neck results in a fusion of the two transcription factor genes MYB and NFIB. Here we demonstrate, for the first time, that benign sporadic, dermal cylindromas also express the MYB-NFIB gene fusion. RT-PCR and immunohistochemical analyses revealed that eight of 12 analysed tumours (67%) expressed MYB-NFIB fusion transcripts and/or stained positive for MYB protein. Nucleotide sequence analyses confirmed that the composition of the chimeric transcript variants identified was identical to that in ACC, suggesting a similar molecular mechanism of activation of MYB in cylindroma as in ACC. In contrast, no evidence for the presence of the MYB-NFIB fusion was found in other types of basaloid skin and salivary gland tumours, indicating that the fusion indeed has a restricted expression pattern. Our findings broaden the spectrum of neoplasms associated with MYB oncogene activation and reveal a novel genetic link between ACC and dermal cylindroma. These results, together with our previous observations, further strengthen the evidence for common molecular pathways of importance for the development of both benign and malignant breast, salivary and adnexal tumours.
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| 4. |
- Johansson, Henrik J., et al.
(författare)
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Retinoic acid receptor alpha is associated with tamoxifen resistance in breast cancer
- 2013
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Ingår i: Nature Communications. - : Nature Publishing Group: Nature Communications. - 2041-1723. ; 4:3175
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Tidskriftsartikel (refereegranskat)abstract
- About one-third of oestrogen receptor alpha-positive breast cancer patients treated with tamoxifen relapse. Here we identify the nuclear receptor retinoic acid receptor alpha as a marker of tamoxifen resistance. Using quantitative mass spectrometry-based proteomics, we show that retinoic acid receptor alpha protein networks and levels differ in a tamoxifen-sensitive (MCF7) and a tamoxifen-resistant (LCC2) cell line. High intratumoural retinoic acid receptor alpha protein levels also correlate with reduced relapse-free survival in oestrogen receptor alpha-positive breast cancer patients treated with adjuvant tamoxifen solely. A similar retinoic acid receptor alpha expression pattern is seen in a comparable independent patient cohort. An oestrogen receptor alpha and retinoic acid receptor alpha ligand screening reveals that tamoxifen-resistant LCC2 cells have increased sensitivity to retinoic acid receptor alpha ligands and are less sensitive to oestrogen receptor alpha ligands compared with MCF7 cells. Our data indicate that retinoic acid receptor alpha may be a novel therapeutic target and a predictive factor for oestrogen receptor alpha-positive breast cancer patients treated with adjuvant tamoxifen.
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| 5. |
- Karlsson, Per, 1963, et al.
(författare)
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Patterns and risk factors for locoregional failures after mastectomy for breast cancer: an International Breast Cancer Study Group report
- 2012
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534. ; 23:11, s. 2852-2858
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Tidskriftsartikel (refereegranskat)abstract
- Rates and risk factors of local, axillary and supraclavicular recurrences can guide patient selection and target for postmastectomy radiotherapy (PMRT). Local, axillary and supraclavicular recurrences were evaluated in 8106 patients enrolled in 13 randomized trials. Patients received chemotherapy and/or endocrine therapy and mastectomy without radiotherapy. Median follow-up was 15.2 years. Ten-year cumulative incidence for chest wall recurrence of > 15% was seen in patients aged < 40 years (16.1%), with >= 4 positive nodes (16.5%) or 0-7 uninvolved nodes (15.1%); for supraclavicular failures > 10%: >= 4 positive nodes (10.2%); for axillary failures of > 5%: aged < 40 years (5.1%), unknown primary tumor size (5.2%), 0-7 uninvolved nodes (5.2%). In patients with 1-3 positive nodes, 10-year cumulative incidence for chest wall recurrence of > 15% were age < 40, peritumoral vessel invasion or 0-7 uninvolved nodes. Age, number of positive nodes and number of uninvolved nodes were significant parameters for each locoregional relapse site. PMRT to the chest wall and supraclavicular fossa is supported in patients with >= 4 positive nodes. With 1-3 positive nodes, chest wall PMRT may be considered in patients aged < 40 years, with 0-7 uninvolved nodes or with vascular invasion. The findings do not support PMRT to the dissected axilla.
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| 6. |
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| 7. |
- Möllerström, Elin, et al.
(författare)
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Up-regulation of cell cycle arrest protein BTG2 correlates with increased overall survival in breast cancer, as detected by immunohistochemistry using tissue microarray.
- 2010
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Ingår i: BMC cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT: BACKGROUND: Previous studies have shown that the ADIPOR1, ADORA1, BTG2 and CD46 genes differ significantly between long-term survivors of breast cancer and deceased patients, both in levels of gene expression and DNA copy numbers. The aim of this study was to characterize the expression of the corresponding proteins in breast carcinoma and to determine their correlation with clinical outcome. METHODS: Protein expression was evaluated using immunohistochemistry in an independent breast cancer cohort of 144 samples represented on tissue microarrays. Fisher's exact test was used to analyze the differences in protein expression between dead and alive patients. We used Cox-regression multivariate analysis to assess whether the new markers predict the survival status of the patients better than the currently used markers. RESULTS: BTG2 expression was demonstrated in a significantly lower proportion of samples from dead patients compared to alive patients, both in overall expression (P=0.026) and cell membrane specific expression (P=0.013), whereas neither ADIPOR1, ADORA1 nor CD46 showed differential expression in the two survival groups. Furthermore, a multivariate analysis showed that a model containing BTG2 expression in combination with HER2 and Ki67 expression along with patient age performed better than a model containing the currently used prognostic markers (tumour size, nodal status, HER2 expression, hormone receptor status, histological grade, and patient age). Interestingly, BTG2 has previously been described as a tumour suppressor gene involved in cell cycle arrest and p53 signalling. CONCLUSIONS: We conclude that high-level BTG2 protein expression correlates with prolonged survival in patients with breast carcinoma.
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| 8. |
- Nilsson, Jeanette, 1962, et al.
(författare)
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Nuclear Janus-activated kinase 2/nuclear factor 1-C2 suppresses tumorigenesis and epithelial-to-mesenchymal transition by repressing Forkhead box F1.
- 2010
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Ingår i: Cancer research. - 1538-7445. ; 70:5, s. 2020-2029
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Tidskriftsartikel (refereegranskat)abstract
- Progression to metastasis is the proximal cause of most cancer-related mortality. Yet much remains to be understood about what determines the spread of tumor cells. This paper describes a novel pathway in breast cancer that regulates epithelial-to-mesenchymal transition (EMT), motility, and invasiveness. We identify two transcription factors, nuclear factor 1-C2 (NF1-C2) and Forkhead box F1 (FoxF1), downstream of prolactin/nuclear Janus-activated kinase 2, with opposite effects on these processes. We show that NF1-C2 is lost during mammary tumor progression and is almost invariably absent from lymph node metastases. NF1-C2 levels in primary tumors correlate with better patient survival. Manipulation of NF1-C2 levels by expression of a stabilized version or using small interfering RNA showed that NF1-C2 counteracts EMT, motility, invasiveness, and tumor growth. FoxF1 was found to be a direct repressed target of NF1-C2. We provide the first evidence for a role of FoxF1 in cancer and in the regulation of EMT in cells of epithelial origin. Overexpression of FoxF1 was associated with a mesenchymal phenotype, increased invasiveness in vitro, and enhanced growth of breast carcinoma xenografts in nude mice. The relevance of these findings is strengthened by the correlation between FoxF1 expression and a mesenchymal phenoype in breast cancer cell isolates, consistent with the interpretation that FoxF1 promotes invasion and metastasis.
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| 9. |
- Parris, Toshima Z, 1978, et al.
(författare)
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Clinical implications of gene dosage and gene expression patterns in diploid breast carcinoma.
- 2010
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Ingår i: Clinical cancer research : an official journal of the American Association for Cancer Research. - 1078-0432. ; 16:15, s. 3860-74
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Tidskriftsartikel (refereegranskat)abstract
- Deregulation of key cellular pathways is fundamental for the survival and expansion of neoplastic cells. In cancer, regulation of gene transcription can be mediated in a variety of ways. The purpose of this study was to assess the impact of gene dosage on gene expression patterns and the effect of other mechanisms on transcriptional levels, and to associate these genomic changes with clinicopathologic parameters.
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| 10. |
- Parris, Toshima Z, 1978, et al.
(författare)
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Clinical relevance of breast cancer-related genes as potential biomarkers for oral squamous cell carcinoma
- 2014
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Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Background: Squamous cell carcinoma of the oral cavity (OSCC) is a common cancer form with relatively low 5-year survival rates, due partially to late detection and lack of complementary molecular markers as targets for treatment. Molecular profiling of head and neck cancer has revealed biological similarities with basal-like breast and lung carcinoma. Recently, we showed that 16 genes were consistently altered in invasive breast tumors displaying varying degrees of aggressiveness. Methods: To extend our findings from breast cancer to another cancer type with similar characteristics, we performed an integrative analysis of transcriptomic and proteomic data to evaluate the prognostic significance of the 16 putative breast cancer-related biomarkers in OSCC using independent microarray datasets and immunohistochemistry. Predictive models for disease-specific (DSS) and/or overall survival (OS) were calculated for each marker using Cox proportional hazards models. Results: We found that CBX2, SCUBE2, and STK32B protein expression were associated with important clinicopathological features for OSCC (peritumoral inflammatory infiltration, metastatic spread to the cervical lymph nodes, and tumor size). Consequently, SCUBE2 and STK32B are involved in the hedgehog signaling pathway which plays a pivotal role in metastasis and angiogenesis in cancer. In addition, CNTNAP2 and S100A8 protein expression were correlated with DSS and OS, respectively. Conclusions: Taken together, these candidates and the hedgehog signaling pathway may be putative targets for drug development and clinical management of OSCC patients.
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