| 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. |
- Biermann, Jana, et al.
(författare)
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Clonal relatedness in tumour pairs of breast cancer patients.
- 2018
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Ingår i: Breast cancer research : BCR. - : Springer Science and Business Media LLC. - 1465-542X. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- Molecular classification of tumour clonality is currently not evaluated in multiple invasive breast carcinomas, despite evidence suggesting common clonal origins. There is no consensus about which type of data (e.g. copy number, mutation, histology) and especially which statistical method is most suitable to distinguish clonal recurrences from independent primary tumours.Thirty-seven invasive breast tumour pairs were stratified according to laterality and time interval between the diagnoses of the two tumours. In a multi-omics approach, tumour clonality was analysed by integrating clinical characteristics (n = 37), DNA copy number (n = 37), DNA methylation (n = 8), gene expression microarray (n = 7), RNA sequencing (n = 3), and SNP genotyping data (n = 3). Different statistical methods, e.g. the diagnostic similarity index (SI), were used to classify the tumours as clonally related recurrences or independent primary tumours.The SI and hierarchical clustering showed similar tendencies and the highest concordance with the other methods. Concordant evidence for tumour clonality was found in 46% (17/37) of patients. Notably, no association was found between the current clinical guidelines and molecular tumour features.A more accurate classification of clonal relatedness between multiple breast tumours may help to mitigate treatment failure and relapse by integrating tumour-associated molecular features, clinical parameters, and statistical methods. Guidelines need to be defined with exact thresholds to standardise clonality testing in a routine diagnostic setting.
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| 3. |
- Biermann, Jana, et al.
(författare)
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Tumour clonality in paired invasive breast carcinomas
- 2019
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Ingår i: Cancer Research. - 0008-5472.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Background: Multiple invasive breast tumours may represent either independent primary tumours or clonal recurrences of the first tumour, where the same progenitor cell gives rise to all of the detected tumours. Consequently, the driver events for the progenitor cell need to have been identical in early tumour development. Molecular classification of tumour clonality is not currently evaluated in multiple invasive breast carcinomas, despite evidence suggesting common clonal origins. Furthermore, there is no consensus about which type of biological data (e.g. copy number, mutation, histology) and especially which statistical method is most suitable to distinguish clonal recurrences from independent primary tumours. Methods: Thirty-seven invasive breast tumour pairs were stratified by laterality (bilateral vs. ipsilateral) and the time interval between the diagnoses of the first and second tumours (synchronous vs. metachronous). Both tumours from the same patient were analysed by integrating clinical characteristics (n = 37), DNA copy number (n = 37), DNA methylation (n = 8), gene expression microarray (n = 7), RNA sequencing (n = 3), and SNP genotyping data (n = 3). Different statistical methods, e.g. the diagnostic similarity index (SI), distance measure, shared segment analysis etc., were used to classify the tumours from the same patient as clonally related recurrences or independent primary tumours. Results: The SI applied on DNA copy numbers derived from aCGH (array comparative genomic hybridization) data was determined as the strongest indicator of clonal relatedness as it showed the highest concordance with all other methods. The distance measure was the most conservative method and the shared segment analysis most liberal. Concordant evidence for tumour clonality was found in 46% (17/37) of the patients. Notably, no significant association was found between the clinical characteristics and molecular tumour features. Conclusions: A more accurate classification of clonal relatedness between multiple breast tumours may help to mitigate treatment failure and relapse by integrating tumour-associated molecular features, clinical parameters, and statistical methods. In cases of extremely similar or different tumour pairs, the results showed consistency regardless of the method used. The SI can be easily integrated into clinical routine using FFPE samples to obtain copy number data. However, clinical guidelines with exact thresholds need to be defined to standardize clonality testing in a routine diagnostic setting.
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| 4. |
- Larsson, Peter, et al.
(författare)
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Optimization of cell viability assays to improve replicability and reproducibility of cancer drug sensitivity screens.
- 2020
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Cancer drug development has been riddled with high attrition rates, in part, due to poor reproducibility of preclinical models for drug discovery. Poor experimental design and lack of scientific transparency may cause experimental biases that in turn affect data quality, robustness and reproducibility. Here, we pinpoint sources of experimental variability in conventional 2D cell-based cancer drug screens to determine the effect of confounders on cell viability for MCF7 and HCC38 breast cancer cell lines treated with platinum agents (cisplatin and carboplatin) and a proteasome inhibitor (bortezomib). Variance component analysis demonstrated that variations in cell viability were primarily associated with the choice of pharmaceutical drug and cell line, and less likely to be due to the type of growth medium or assay incubation time. Furthermore, careful consideration should be given to different methods of storing diluted pharmaceutical drugs and use of DMSO controls due to the potential risk of evaporation and the subsequent effect on dose-response curves. Optimization of experimental parameters not only improved data quality substantially but also resulted in reproducible results for bortezomib- and cisplatin-treated HCC38, MCF7, MCF-10A, and MDA-MB-436 cells. Taken together, these findings indicate that replicability (the same analyst re-performs the same experiment multiple times) and reproducibility (different analysts perform the same experiment using different experimental conditions) for cell-based drug screens can be improved by identifying potential confounders and subsequent optimization of experimental parameters for each cell line.
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| 5. |
- Larsson, Peter, et al.
(författare)
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Pan-cancer analysis of genomic and transcriptomic data reveals the prognostic relevance of human proteasome genes in different cancer types.
- 2022
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Ingår i: BMC cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 22
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Tidskriftsartikel (refereegranskat)abstract
- The human proteasome gene family (PSM) consists of 49 genes that play a crucial role in cancer proteostasis. However, little is known about the effect of PSM gene expression and genetic alterations on clinical outcome in different cancer forms.Here, we performed a comprehensive pan-cancer analysis of genetic alterations in PSM genes and the subsequent prognostic value of PSM expression using data from The Cancer Genome Atlas (TCGA) containing over 10,000 samples representing up to 33 different cancer types. External validation was performed using a breast cancer cohort and KM plotter with four cancer types.The PSM genetic alteration frequency was high in certain cancer types (e.g. 67%; esophageal adenocarcinoma), with DNA amplification being most common. Compared with normal tissue, most PSM genes were predominantly overexpressed in cancer. Survival analysis also established a relationship with PSM gene expression and adverse clinical outcome, where PSMA1 and PSMD11 expression were linked to more unfavorable prognosis in ≥ 30% of cancer types for both overall survival (OS) and relapse-free interval (PFI). Interestingly, PSMB5 gene expression was associated with OS (36%) and PFI (27%), and OS for PSMD2 (42%), especially when overexpressed.These findings indicate that several PSM genes may potentially be prognostic biomarkers and novel therapeutic targets for different cancer forms.
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| 6. |
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| 7. |
- 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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| 8. |
- Axelsson, Lars, et al.
(författare)
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Prognostic factors for head and neck cancer of unknown primary including the impact of human papilloma virus infection
- 2017
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Ingår i: Journal of Otolaryngology-Head & Neck Surgery. - : Springer Science and Business Media LLC. - 1916-0216. ; 46
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Tidskriftsartikel (refereegranskat)abstract
- Background: Head and neck cancer of unknown primary (HNCUP) is rare and prospective studies are lacking. The impact of different prognostic factors such as age and N stage is not completely known, the optimal treatment is not yet established, and the reported survival rates vary. In the last decade, human papilloma virus (HPV) has been identified as a common cause of and important prognostic factor in oropharyngeal cancer, and there is now growing interest in the importance of HPV for HNCUP. The aim of the present study on curatively treated HNCUP was to investigate the prognostic importance of different factors, including HPV status, treatment, and overall survival. Methods: A search for HNCUP was performed in the Swedish Cancer Registry, Western health district, between the years 1992-2009. The medical records were reviewed, and only patients with squamous cell carcinoma or undifferentiated carcinoma treated with curative intent were included. The tumor specimens were retrospectively analyzed for HPV with p16 immunostaining. Results: Sixty- eight patients were included. The mean age was 59 years. The majority were males, and had N2 tumors. Sixty-nine percent of the tumors were HPV positive using p16 staining. Patients who were older than 70 years, patients with N3-stage tumors, and patients with tumors that were p16 negative had a significantly worse prognosis. The overall 5-year survival rate for patients with p16-positive tumors was 88% vs 61% for p16- negative tumors. Treatment with neck dissection and postoperative radiation or (chemo) radiation had 81 and 88% 5- year survival rates, respectively. The overall and disease- free 5-year survival rates for all patients in the study were 82 and 74%. Conclusions: Curatively treated HNCUP had good survival. HPV infection was common. Independent prognostic factors for survival were age over 70 years, HPV status and N3 stage. We recommend that HPV analysis should be performed routinely for HNCUP. Treatment with neck dissection and postoperative radiation or (chemo) radiation showed similar survival rates.
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| 9. |
- Barzó, P, et al.
(författare)
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[Giant cell interstitial pneumonia]. : Oriássejtes interstitialis pneumonia.
- 1998
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Ingår i: Orvosi hetilap. - 0030-6002. ; 139:51, s. 3079-83
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Tidskriftsartikel (refereegranskat)abstract
- GIP is a rarely occurring disorder. There is only few literature from its first description. Authors observed the course of GIP in the case of a 54 year old female patient in the form of bilateral disseminated microfocal pulmonary shadows, increased reticular outline with associated respiratory insufficiency. Open fine needle pulmonary biopsy proved giant cell desquamative alveolitis with help of light- and electronmicroscopical and histochemical examinations. Although possibility of exogenic, inhalative factor or/and infectious origin arose in causing the disease, disposition from the patient's actual immunological status could had helped the evolution of the disease. This fact seemed to be supported by the histologically proven associated dermatitis purpurica pigmentosa (Schamberg disease). With methylprednisolon therapy full radiological recovery occurred, while Schamberg disease was little influenced by the above mentioned therapy. The patient is pulmonologically symptom-free and without complaint after 1 year without any steroid-medication.
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| 10. |
- Biermann, Jana, et al.
(författare)
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A 17-marker panel for global genomic instability in breast cancer.
- 2020
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Ingår i: Genomics. - : Elsevier BV. - 0888-7543 .- 1089-8646. ; 112:2, s. 1151-1161
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Tidskriftsartikel (refereegranskat)abstract
- Genomic instability is a hallmark of cancer that plays a pivotal role in breast cancer development and evolution. A number of existing prognostic gene expression signatures for breast cancer are based on proliferation-related genes. Here, we identified a 17-marker panel associated with genome stability. A total of 136 primary breast carcinomas were stratified by genome stability. Matched gene expression profiles showed an innate segregation based on genome stability. We identified a 17-marker panel stratifying the training and validation cohorts into high- and low-risk patients. The 17 genes associated with genomic instability strongly impacted clinical outcome in breast cancer. Pathway analyses determined chromosome organisation, cell cycle regulation, and RNA processing as the underlying biological processes, thereby offering options for drug development and treatment tailoring. Our work supports the applicability of the 17-marker panel to improve clinical outcome prediction for breast cancer patients based on a signature accounting for genomic instability.
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