| 1. |
- Alaiya, A, et al.
(author)
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Polypeptide expression in prostate hyperplasia and prostate adenocarcinoma
- 2000
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In: Analytical cellular pathology : the journal of the European Society for Analytical Cellular Pathology. - : Hindawi Limited. - 0921-8912. ; 21:1, s. 1-9
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Journal article (peer-reviewed)abstract
- Cells were collected from prostate hyperplasias (n=6) and prostate carcinomas (n=6) and subjected to two‐dimensional gel electrophoresis (2‐DE). The resulting polypeptide patterns were analysed with the PDQUEST computer software. Malignant tumors showed significant increases in the level of expression of proliferating cell nuclear antigen (PCNA), calreticulin, HSP 90 and pHSP 60, oncoprotein 18(v), elongation factor 2, glutathione‐S‐transferaseπ(GST‐π), superoxide dismutase and triose phosphate isomerase. In addition, decreases in the levels of tropomyosin‐1 and 2 and cytokeratin 18 were observed in prostate carcinomas compared to prostate hyperplasias. This pattern of alterations is similar to that observed in other carcinomas in our previous studies. All malignant tumors showed simultaneous alterations in 5 or more of 9 markers studied, whereas only one case of benign hyperplasia showed alterations in 5 markers. The EST‐data base for prostate tumors available from NCI (CGAP) was searched for the expression of the mRNAs corresponding to proteins identified in our gels. Large differences in the relative expression of mRNAs and proteins were observed. Our data show alterations in the pattern of polypeptide expression in prostate carcinomas which are similar to those observed in other carcinomas.
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| 2. |
- Alaiya, Ayodele A
(author)
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Cancer proteomics : characterisation of protein expression in human epithelial tumours
- 1999
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Doctoral thesis (other academic/artistic)abstract
- Defining differences in protein expression between tumour cells of various degrees of malignancy is a first step in the development of markers for tumour diagnosis. In this thesis, the expression of multiple proteins in benign and malignant human ovarian, breast and prostate tumours was examined using two-dimensional gel electrophoresis (2-DE). We were able to show a similar pattern of expression of a set of ten proteins between benign and malignant cells in all three tumour types examined. Cytokeratins and high molecular weight tropomyosins were consistently down-regulated in carcinomas, whereas stress proteins (HSP90, HSP60 and calreticulin) were upregulated. This finding suggests a high degree of homology in the expression of these proteins among different tumour types of epithelial origin. An attempt to apply principal component analysis of quantitative 2-DE data for diagnosis of ovarian cancer is presented. Data of the expression of 170 polypeptides was compiled from 22 tumours and used to construct a model for classification into benign, borderline and malignant ovarian tumours. When the model was tested using 18 tumours, 11 tumours (61%) were correctly classified. We were encouraged by this result and intend to increase the number of tumours used to construct the model. Future work will show whether it is possible to accurately classify tumours by their gene expression profiles. Twenty proteins in the 2-DE maps of breast, lung and ovarian tumours were identified using mass spectrometry. Some of these proteins were found to consist of polypeptide fragments, suggesting the occurrence of proteolytic processing of polypeptides in these tumours. The process of tumour progression leads to the development of tumour heterogeneity. The 2-DE technique was used to study intra- and intertumour heterogeneity. Our results suggested that the degree of intertumour heterogeneity was substantial, whereas intratumoural variations were less pronounced. We conclude that 2-DE separation of proteins in human tumours can yield new information relevant to the understanding of tumour biology. We believe that this line of research will lead to improved diagnostic and predictive tools.
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| 8. |
- Carlén, Lina M, et al.
(author)
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Proteome analysis of skin distinguishes acute guttate from chronic plaque psoriasis.
- 2005
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In: Journal of Investigative Dermatology. - 0022-202X .- 1523-1747. ; 124:1
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Journal article (peer-reviewed)abstract
- Psoriasis is a disease with considerable heterogeneity in clinical presentation. This is the first study using two-dimensional gel electrophoresis to compare global protein expression patterns in lesional and non-lesional skin from subjects with acute guttate psoriasis associated with streptococcal throat infection and chronic plaque psoriasis. Samples from experimentally induced contact eczema and normal skin from healthy controls were also included. Proteins with statistically significant differences in expression were used in hierarchical cluster analyses resulting in separation of the different samples into groups. Chronic plaque and guttate psoriasis samples were distinctly separated, indicating that they represent discrete phenotypes at the protein expression level. Interestingly, there was a trend in which guttate psoriasis lesions clustered closer to eczema than to chronic plaque psoriasis lesions, indicating that the duration of the inflammatory reaction may affect clustering. Several of the differentially expressed proteins were identified by mass spectrometry.
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| 11. |
- Hellman, Kristina, et al.
(author)
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Differential tissue-specific protein markers of vaginal carcinoma
- 2009
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In: British Journal of Cancer. - : Cancer Research UK. - 0007-0920 .- 1532-1827. ; 100:8, s. 1303-1314
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Research review (peer-reviewed)abstract
- The objective was to identify proteins differentially expressed in vaginal cancer to elucidate relevant cancer-related proteins. A total of 16 fresh-frozen tissue biopsies, consisting of 5 biopsies from normal vaginal epithelium, 6 from primary vaginal carcinomas and 5 from primary cervical carcinomas, were analysed using two-dimensional gel electrophoresis (2-DE) and MALDI-TOF mass spectrometry. Of the 43 proteins identified with significant alterations in protein expression between non-tumourous and tumourous tissue, 26 were upregulated and 17 were downregulated. Some were similarly altered in vaginal and cervical carcinoma, including cytoskeletal proteins, tumour suppressor proteins, oncoproteins implicated in apoptosis and proteins in the ubiquitin-proteasome pathway. Three proteins were uniquely altered in vaginal carcinoma (DDX48, erbB3-binding protein and biliverdin reductase) and five in cervical carcinoma (peroxiredoxin 2, annexin A2, sarcomeric tropomyosin kappa, human ribonuclease inhibitor and prolyl-4-hydrolase beta). The identified proteins imply involvement of multiple different cellular pathways in the carcinogenesis of vaginal carcinoma. Similar protein alterations were found between vaginal and cervical carcinoma suggesting common tumourigenesis. However, the expression level of some of these proteins markedly differs among the three tissue specimens indicating that they might be useful molecular markers.
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| 13. |
- Linder, S, et al.
(author)
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Serum efficacy biomarkers for oncology
- 2009
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In: Biomarkers in medicine. - : Future Medicine Ltd. - 1752-0371 .- 1752-0363. ; 3:1, s. 47-54
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Journal article (peer-reviewed)abstract
- Considerable interest has emerged in serum biomarkers that can be used to evaluate early effects of cancer therapeutics. Such efficacy biomarkers are expected to become valuable both for routine clinical care and for anticancer drug development. Here, we review the literature on serum efficacy biomarkers. We discuss how data using such markers can be interpreted, particularly with regard to the issue of specificity of different markers. An important question is whether biomarker response evaluation is expected to be congruent with evaluation by traditional anatomical methods. We argue that they may not be – biomarkers are expected to provide information with regard to induction of tumor cell death that will not necessarily reflect clinical outcome.
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| 15. |
- Liu, Zhaoxu, et al.
(author)
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Somatostatin effects on the proteome of the LNCaP cell-line
- 2007
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In: International Journal of Oncology. - : Spandidos Publications. - 1019-6439 .- 1791-2423. ; 30:5, s. 1173-1179
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Journal article (peer-reviewed)abstract
- Some clinical results indicate that somatostatin (sms) might be useful in the treatment of advanced prostate cancer (HRPC). Because of its transient in vivo half-life only more stable derivatives of sms are of interest in this context. Recent studies have shown that natural sms can be conjugated to a carbohydrate (smsdx) with preservation of sms-like effects on the prostatic tumor cell proteome. The present study identifies some of the affected proteins in an effort to elucidate pathways and proteins that might be of importance for the potential usefulness of sms treatment in HRPC. After incubating the LNCaP cell-line with sms14/smsdx, comparative proteomics was used for analysing and identifying affected proteins. Protein expression patterns were analysed with two-dimensional polyacrylamide gel electrophoresis and mass spectrometry. Catalytic mitochondrial and mitochondrial-associated proteins were significantly affected (fold change approximately 2 or higher) and they were in general up-regulated. Apoptosis-related proteins were both up-regulated (VDAC1, VDAC2) and down-regulated (PRDX2, TCTP). The fold change was >2 for PRDX2 and <2 for the others. There was a strong agreement between sms and smsdx on the up- and down-regulation of proteins. Sms/smsdx triggered up-regulation of catalytic mitochondrial proteins and seemed to affect apoptosis-related proteins. This could indicate important pathways on which smsdx might be able to curb the progression of HRPC. The results encourage a pending clinical phase II study.
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| 16. |
- Marquez, M, et al.
(author)
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Poly-guanidine shows high cytotoxicity in glioma cell cultures and glioma stem cells
- 2022
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In: Investigational new drugs. - : Springer Science and Business Media LLC. - 1573-0646 .- 0167-6997. ; 40:3, s. 565-575
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Journal article (peer-reviewed)abstract
- Glioblastoma multiforme (GBM) is a malignant CNS tumor with a poor prognosis. GBM shows aberrant glycosylation with hypersialylation. This property is a potential target for therapy. This study investigates the growth inhibitory efficacy of poly-guanidine (GuaDex), with an affinity for sialic acid (Sia). Glioma cell cultures and patient-derived glioma cell lines (PDGCLs) expressing Prominin-1 (CD133) were used. Human fibroblasts and astrocyte-derived cells were used as controls. Temozolomide (standard GBM drug, TMZ) and DMSO were used as a comparison. GuaDex at 1–10 µM concentrations, were incubated for 3.5–72 h and with PDGCLs cells for 6–24 h. The cytotoxicity was estimated with a fluorometric cytotoxicity assay (FMCA). Fluorescence-labelled GuaDex was used to study the cell interactions. Sia expression was confirmed with a fluorescence labelled Sia binding lectin. Expression of glial fibrillary acidic protein was determined. GuaDex induction of growth inhibition was fast, showing after less than 5 min incubation while the control cells were not affected even after 50 min incubation. The growth inhibitory effect on PDGCLs spheroids was persistent still showing after 4 weeks post-treatment. The growth inhibition of GuaDex was induced at low µM concentrations while TMZ induced only a slight inhibition at mM concentrations. GuaDex efficacy appears significant and warrants further studies.
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| 17. |
- Roblick, U.J., et al.
(author)
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Undifferentiated pelvic adenocarcinomas : diagnostic potential of protein profiling and multivariate analysis
- 2008
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In: International Journal of Colorectal Disease. - : Springer Science and Business Media LLC. - 0179-1958 .- 1432-1262. ; 23:5, s. 483-491
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Journal article (peer-reviewed)abstract
- BACKGROUND AND AIMS: Despite improved techniques, the determination of tumor origin in poorly differentiated adenocarcinomas still remains a challenge for the pathologist. Here we report the use of protein profiling combined with principal component analysis to improve diagnostic decision-making in tumor samples, in which standard pathologic investigations cannot present reliable results. MATERIALS AND METHODS: A poorly differentiated adenocarcinoma of unknown origin located in the pelvis, infiltrating the sigmoid colon as well as the ovary, served as a model to evaluate our proteomic approach. Firstly, we characterized the protein expression profiles from eight advanced colon and seven ovarian adenocarcinomas using two-dimensional gel electrophoresis (2-DE). Qualitative and quantitative patterns were recorded and compared to the tumor of unknown origin. Based on these protein profiles, match sets from the different tumors were created. Finally, a multivariate principal component analysis was applied to the entire 2-DE data to disclose differences in protein patterns between the different tumors. RESULTS: Over 89% of the unknown tumor sample spots could be matched with the colon standard gel, whereas only 63% of the spots could be matched with the ovarian standard. In addition, principal component analysis impressively displayed the clustering of the unknown case within the colon cancer samples, whereas this case did not cluster at all within the group of ovarian adenocarcinomas. CONCLUSION: These results show that 2-DE protein expression profiling combined with principal component analysis is a sensitive method for diagnosing undifferentiated adenocarcinomas of unknown origin. The described approach can contribute greatly to diagnostic decision-making and, with further technical improvements and a higher throughput, become a powerful tool in the armentarium of the pathologist.
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| 18. |
- Sun, B, et al.
(author)
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Biophysical and physiological properties of a modified porcine surfactant enriched with surfactant protein A
- 1997
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In: The European respiratory journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 10:9, s. 1967-1974
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Journal article (peer-reviewed)abstract
- Surfactant protein A (SP-A), a major protein component of natural pulmonary surfactant, is absent in exogenous surfactants currently used in clinical practice. We investigated the physical and physiological properties of one of these modified natural surfactants (Curosurf) after enrichment with 5% SP-A (SP-A-Curosurf). A pulsating bubble system was used for in vitro assessments and ventilated newborn rabbits for evaluation of in vivo effects. In the presence of various potential inhibitors (meconium 5 mg.mL-1, fibrinogen 5 mg.mL-1, albumin 25 mg.mL-1, or whole serum proteins 25 mg.mL-1), Curosurf at a concentration of 5 mg.mL-1 was inactivated while SP-A-Curosurf and natural porcine surfactant at the same concentration had normal maximum and minimum surface tension. This protective effect of SP-A was calcium dependent. In immature newborn rabbits, the improvement of lung-thorax compliance observed after treatment with 100 mg.kg-1 of SP-A-Curosurf was equivalent to that obtained with 200 mg.kg-1 of Curosurf. Similarly, in near-term newborn rabbits with respiratory failure induced by instillation of fibrinogen via the airways, the increase in compliance after administration of 100 mg.kg-1 of SP-A-Curosurf corresponded to that seen after treatment with 200 mg.kg-1 of Curosurf, whereas Curosurf at a dose of 100 mg.kg-1 had no substantial effect. Our data thus indicate that surfactant protein A increases the resistance of Curosurf to inactivation under in vivo conditions.
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