| 1. |
- Ansari, Daniel, et al.
(författare)
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Analysis of MUC4 Expression in Human Pancreatic Cancer Xenografts in Immunodeficient Mice.
- 2014
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Ingår i: Anticancer research. - 1791-7530. ; 34:8, s. 3905-3910
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Tidskriftsartikel (refereegranskat)abstract
- Mucin 4 (MUC4) is a cell surface glycoprotein that is overexpressed in most pancreatic tumors. The aim of the present study was to characterize MUC4 expression in experimental pancreatic cancer in order to clarify the correlation between MUC4 and pancreatic cancer histology in vivo.
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| 2. |
- Ansari, Daniel, et al.
(författare)
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Pancreatic cancer : Yesterday, today and tomorrow
- 2016
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Ingår i: Future Oncology. - : Future Medicine Ltd. - 1479-6694 .- 1744-8301. ; 12:16, s. 1929-1946
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Tidskriftsartikel (refereegranskat)abstract
- Pancreatic cancer is one of our most lethal malignancies. Despite substantial improvements in the survival rates for other major cancer forms, pancreatic cancer survival rates have remained relatively unchanged since the 1960s. Pancreatic cancer is usually detected at an advanced stage and most treatment regimens are ineffective, contributing to the poor overall prognosis. Herein, we review the current understanding of pancreatic cancer, focusing on central aspects of disease management from radiology, surgery and pathology to oncology.
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| 3. |
- Ansari, Daniel, et al.
(författare)
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Protein deep sequencing applied to biobank samples from patients with pancreatic cancer.
- 2015
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Ingår i: Journal of Cancer Research and Clinical Oncology. - : Springer Science and Business Media LLC. - 1432-1335 .- 0171-5216. ; 141:2, s. 369-380
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Tidskriftsartikel (refereegranskat)abstract
- Pancreatic cancer is commonly detected at advanced stages when the tumor is no longer amenable to surgical resection. Therefore, finding biomarkers for early stage disease is urgent. Here, we show that high-definition mass spectrometry (HDMS(E)) can be used to identify serum protein alterations associated with early stage pancreatic cancer.
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| 4. |
- Ansari, Daniel, et al.
(författare)
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The role of quantitative mass spectrometry in the discovery of pancreatic cancer biomarkers for translational science.
- 2014
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Ingår i: Journal of Translational Medicine. - : Springer Science and Business Media LLC. - 1479-5876. ; 12:1
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Forskningsöversikt (refereegranskat)abstract
- In the post-genomic era, it has become evident that genetic changes alone are not sufficient to understand most disease processes including pancreatic cancer. Genome sequencing has revealed a complex set of genetic alterations in pancreatic cancer such as point mutations, chromosomal losses, gene amplifications and telomere shortening that drive cancerous growth through specific signaling pathways. Proteome-based approaches are important complements to genomic data and provide crucial information of the target driver molecules and their post-translational modifications. By applying quantitative mass spectrometry, this is an alternative way to identify biomarkers for early diagnosis and personalized medicine. We review the current quantitative mass spectrometric technologies and analyses that have been developed and applied in the last decade in the context of pancreatic cancer. Examples of candidate biomarkers that have been identified from these pancreas studies include among others, asporin, CD9, CXC chemokine ligand 7, fibronectin 1, galectin-1, gelsolin, intercellular adhesion molecule 1, insulin-like growth factor binding protein 2, metalloproteinase inhibitor 1, stromal cell derived factor 4, and transforming growth factor beta-induced protein. Many of these proteins are involved in various steps in pancreatic tumor progression including cell proliferation, adhesion, migration, invasion, metastasis, immune response and angiogenesis. These new protein candidates may provide essential information for the development of protein diagnostics and targeted therapies. We further argue that new strategies must be advanced and established for the integration of proteomic, transcriptomic and genomic data, in order to enhance biomarker translation. Large scale studies with meta data processing will pave the way for novel and unexpected correlations within pancreatic cancer, that will benefit the patient, with targeted treatment.
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| 5. |
- Bauden, Monika, et al.
(författare)
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Histone profiling reveals the H1.3 histone variant as a prognostic biomarker for pancreatic ductal adenocarcinoma
- 2017
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Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Epigenetic alterations have been recognized as important contributors to the pathogenesis of PDAC. However, the role of histone variants in pancreatic tumor progression is still not completely understood. The aim of this study was to explore the expression and prognostic significance of histone protein variants in PDAC patients. Methods: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was employed for qualitative analysis of histone variants and histone related post-translational modifications (PTMs) in PDAC and normal pancreatic tissues. Survival analysis was conducted using the Kaplan-Meier method and Cox proportional hazards regression. Results: Histone variant H1.3 was found to be differentially expressed (p = 0.005) and was selected as a PDAC specific histone variant candidate. The prognostic role of H1.3 was evaluated in an external cohort of patients with resected PDAC using immunohistochemistry. Intratumor expression of H1.3 was found to be an important risk factor for overall survival in PDAC, with an adjusted HR value of 2.6 (95% CI 1.1-6.1), p = 0.029. Conclusion: We suggest that the intratumor histone H1.3 expression as reported herein, may serve as a new epigenetic biomarker for PDAC.
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| 6. |
- Bläckberg, Jonas, et al.
(författare)
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Flera svenska fall av infektion med rävens dvärgbandmask [Echinococcus multilocularis infection - six cases during two years in Sweden]
- 2020
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Ingår i: Läkartidningen. - : Sveriges Läkarförbund. - 0023-7205 .- 1652-7518. ; 117
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Forskningsöversikt (refereegranskat)abstract
- Alveolar echinococcosis (AE) caused by the fox tapeworm Echinococcus multilocularis is a zoonosis presenting with focal liver lesions and has a poor prognosis without treatment. The disease is common in Central and Eastern Europe but has been highly unusual in Sweden. A suspicion of AE usually arises through radiology and the diagnosis may be confirmed by histology and/or serological antibody detection. AE is treated with radical surgery in combination with anti-helminthic drug therapy. During the last two years six cases of AE have been diagnosed in Sweden. In no case was AE suspected clinically before biopsy. A heightened awareness of AE is needed among Swedish physicians, including radiologists, surgeons and pathologists.
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| 7. |
- Byrling, Johannes, et al.
(författare)
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Expression of fibroblast activation protein and the clinicopathological relevance in distal cholangiocarcinoma
- 2020
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 55:1, s. 82-89
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The current survival of patients with distal cholangiocarcinoma (dCCA) is poor. There is a need to develop new prognostic and predictive biomarkers to improve the survival of patients. Fibroblast activation protein (FAP) expression has been associated with survival in several solid malignancies. The goal of this study was to evaluate the expression pattern and prognostic significance of FAP in dCCA. Materials and methods: FAP expression was examined in 57 resected dCCA specimens and 28 paired lymph node metastasis specimens, as well as 10 benign bile ducts using immunohistochemistry. FAP expression was scored in the epithelial and stromal component of the dCCA specimens. The association between FAP expression and prognosis was evaluated using univariable and multivariable statistical modeling. Results: FAP expression was absent in the benign controls. FAP expression was evident in the epithelial 43 (75%) and stromal compartment 34 (60%) of dCCA. There was no association between epithelial or stromal FAP expression and clinicopathological factors. Epithelial FAP expression (HR 0.4 95% CI 0.20–0.78; p=.007) but not stromal FAP expression was significantly associated with better survival in univariable and multivariable analysis. Conclusions: FAP overexpression is evident in dCCA. There was a positive association between epithelial FAP expression and better survival which merits further evaluation.
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| 8. |
- Byrling, Johannes, et al.
(författare)
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Expression of peritumoral SPARC during distal cholangiocarcinoma progression and correlation with outcome
- 2020
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 55:6, s. 725-731
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Distal cholangiocarcinoma (dCCA) is a malignancy with a dismal prognosis. One of the hallmarks is the presence of a rich desmoplastic stroma believed to contribute to tumor progression and treatment resistance. Secreted protein acidic and rich in cysteine (SPARC) is a matricellular glycoprotein implicated in tumor-stroma interaction with prognostic correlation across several malignancies. The aim of the present study was to evaluate the expression pattern and prognostic significance of SPARC in resected dCCA and paired lymph node metastasis. Materials and methods: SPARC expression was evaluated in 59 resected dCCA samples and 25 paired lymph node metastases as well as 10 benign bile duct samples using immunohistochemistry. Stromal SPARC expression was scored semi quantitatively. Survival was estimated using the Kaplan–Meier method with associated log-rank test. Results: SPARC expression was absent in normal bile ducts. In dCCA, peritumoral stromal SPARC was detectable in 47/59 (80%) of samples with 40/59 (68%) classified as high stromal SPARC expression. There was a significantly lower proportion of SPARC positive stroma in paired lymph node metastasis 17/25 (68%) than the corresponding primary tumors 24/25 (96%) (p =.016). Stromal SPARC expression was associated with the presence of lymph node metastasis; high SPARC expression 31/40 (78%) versus low SPARC expression 9/19 (47%) (p =.013). In the present material there was no significant association between stromal SPARC expression and survival. Conclusions: Stromal SPARC expression occurs frequently in dCCA. Although significantly lower than in primary tumors stromal SPARC is frequently retained in paired lymph node metastasis suggesting a possible role in the metastatic process of dCCA.
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| 9. |
- Byrling, Johannes, et al.
(författare)
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Mass spectrometry-based analysis of formalin-fixed, paraffin-embedded distal cholangiocarcinoma identifies stromal thrombospondin-2 as a potential prognostic marker
- 2020
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Ingår i: Journal of Translational Medicine. - : Springer Science and Business Media LLC. - 1479-5876. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Distal cholangiocarcinoma is an aggressive malignancy with a dismal prognosis. Diagnostic and prognostic biomarkers for distal cholangiocarcinoma are lacking. The aim of the present study was to identify differentially expressed proteins between distal cholangiocarcinoma and normal bile duct samples. Methods: A workflow utilizing discovery mass spectrometry and verification by parallel reaction monitoring was used to analyze surgically resected formalin-fixed, paraffin-embedded samples from distal cholangiocarcinoma patients and normal bile duct samples. Bioinformatic analysis was used for functional annotation and pathway analysis. Immunohistochemistry was performed to validate the expression of thrombospondin-2 and investigate its association with survival. Results: In the discovery study, a total of 3057 proteins were identified. Eighty-seven proteins were found to be differentially expressed (q < 0.05 and fold change ≥ 2 or ≤ 0.5); 31 proteins were upregulated and 56 were downregulated in the distal cholangiocarcinoma samples compared to controls. Bioinformatic analysis revealed an abundance of differentially expressed proteins associated with the tumor reactive stroma. Parallel reaction monitoring verified 28 proteins as upregulated and 18 as downregulated in distal cholangiocarcinoma samples compared to controls. Immunohistochemical validation revealed thrombospondin-2 to be upregulated in distal cholangiocarcinoma epithelial and stromal compartments. In paired lymph node metastases samples, thrombospondin-2 expression was significantly lower; however, stromal thrombospondin-2 expression was still frequent (72%). Stromal thrombospondin-2 was an independent predictor of poor disease-free survival (HR 3.95, 95% CI 1.09-14.3; P = 0.037). Conclusion: Several proteins without prior association with distal cholangiocarcinoma biology were identified and verified as differentially expressed between distal cholangiocarcinoma and normal bile duct samples. These proteins can be further evaluated to elucidate their biomarker potential and role in distal cholangiocarcinoma carcinogenesis. Stromal thrombospondin-2 is a potential prognostic marker in distal cholangiocarcinoma.
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| 10. |
- Byrling, Johannes, et al.
(författare)
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Outcome and evaluation of prognostic factors after pancreaticoduodenectomy for distal cholangiocarcinoma
- 2017
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Ingår i: Annals of Gastroenterology. - : Hellenic Society of Gastroenterology. - 1108-7471 .- 1792-7463. ; 30:5, s. 571-577
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Tidskriftsartikel (refereegranskat)abstract
- Background The aim of the present study was to examine the outcomes and prognostic factors after surgery with curative intent for distal cholangiocarcinoma during a modern timespan, in a Swedish tertiary referral center. Methods All patients who underwent pancreaticoduodenectomy for distal cholangiocarcinoma between April 2008 and December 2015 were identified. Survival was estimated using the Kaplan-Meier analysis. Demographic, clinical, laboratory and histopathological data were evaluated for prognostic factors relating to mortality, using univariable and multivariable statistical analysis. Results Fifty-four patients were included. The mean age was 68±8 years and 21 (39%) of the patients were female. Jaundice was present at diagnosis in 73% of the patients. There was no 90-day mortality. Complications graded as Clavien-Dindo ≥3 occurred in 10 (19%) of the patients. Twenty-eight (52%) received adjuvant therapy. Overall survival rates at 1, 3, and 5 years were 80%, 21%, and 9.2%, respectively. Median survival was 22.2 months. The presence of lymph node metastases was found to be the only independent predictor of survival (hazard ratio 2.88, 95% confidence interval 1.22-6.84; P=0.016). The total number of lymph node metastases, lymph node ratio or total number of resected nodes did not improve the prediction. Conclusions We found that the recurrence rate was higher and the survival poorer after surgery for distal cholangiocarcinoma than has previously been reported. Lymph node status at the time of resection was the most important prognostic factor for survival in the current material.
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