| 1. |
- Khalil, Ashraf A., et al.
(författare)
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Biomarker discovery: A proteomic approach for brain cancer profiling
- 2007
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Ingår i: Cancer Science. - : Wiley. - 1349-7006 .- 1347-9032. ; 98:2, s. 201-213
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Tidskriftsartikel (refereegranskat)abstract
- Gliomas in the form of astrocytomas, anaplastic astrocytomas and glioblastomas are the most common brain tumors in humans. Early detection of these cancers is crucial for successful treatment. Proteomics promises the discovery of biomarkers and tumor markers for early detection and diagnosis. In the current study, a differential gel electrophoresis technology coupled with matrix-assisted laser desorption/ionization-time of flight and liquid chromatography-tandem mass spectroscopy was used to investigate tumor-specific changes in the proteome of human brain cancer. Fifty human brain tissues comprising varying diagnostic groups (non-tumor, grade I, grade II, grade III and grade IV) were run in duplicate together with an internal pool sample on each gel. The proteins of interest were automatically picked, in-gel digested and mass spectrometry fingerprinted. Two hundred and eleven protein spots were identified successfully and were collapsed into 91 unique proteins. Approximately 20 of those 91 unique proteins had, to our knowledge, not been reported previously as differentially expressed in human brain cancer. Alb protein, peroxiredoxin 4 and SH3 domain-binding glutamic acid-rich-like protein 3 were upregulated in glioblastoma multiform versus non-tumor tissues. However, aldolase C fructose-biphosphate, creatine kinase, B chain dihydrolipoyl dehydrogenase, enolase 2, fumarate hydratase, HSP60, lactoylglutathione lyase, lucine aminopeptidase, Mu-crystallin homolog, NADH-UO 24, neurofilament triplet L protein, septin 2, stathmin and vacuolar ATP synthase subunit E were downregulated in glioblastoma multiform compared with non-tumor tissues. These differentially expressed proteins provided novel information on the differences existing between normal brain and gliomas, and thus might prove to be useful molecular indicators of diagnostic or prognostic value.
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| 2. |
- Borsics, Tamas, et al.
(författare)
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Subcellular distribution and expression of prenylated Rab acceptor 1 domain family, member 2 (PRAF2) in malignant glioma : Influence on cell survival and migration
- 2010
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Ingår i: Cancer Science. - : Wiley. - 1347-9032 .- 1349-7006. ; 101:7, s. 1624-1631
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Tidskriftsartikel (refereegranskat)abstract
- Our previous studies revealed that the expression of the 19-kDa protein prenylated Rab acceptor 1 domain family, member 2 (PRAF2) is elevated in cancer tissues of the breast, colon, lung, and ovary, when compared to noncancerous tissues of paired samples. PRAF2 mRNA expression also correlated with several genetic and clinical features and is a candidate prognostic marker in the pediatric cancer neuroblastoma. The PRAF2-related proteins, PRAF1 and PRAF3, play multiple roles in cellular processes, including endo/exocytic vesicle trafficking and glutamate uptake. PRAF2 shares a high sequence homology with these family members, but its function remains unknown. In this study, we examined PRAF2 mRNA and protein expression in 20 different human cancer types using Affymetrix microarray and human tissue microarray (TMA) analyses, respectively. In addition, we investigated the subcellular distribution of PRAF2 by immunofluorescence microscopy and cell fractionation studies. PRAF2 mRNA and protein expression was elevated in several cancer tissues with highest levels in malignant glioma. At the molecular level, we detected native PRAF2 in small, vesicle-like structures throughout the cytoplasm as well as in and around cell nuclei of U-87 malignant glioma cells. We further found that monomeric and dimeric forms of PRAF2 are associated with different cell compartments, suggesting possible functional differences. Importantly, PRAF2 down-regulation by RNA interference significantly reduced the cell viability, migration, and invasiveness of U-87 cells. This study shows that PRAF2 expression is elevated in various tumors with exceptionally high expression in malignant gliomas, and PRAF2 therefore presents a candidate molecular target for therapeutic intervention. (Cancer Sci 2010).
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| 3. |
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| 4. |
- Hassan, Saadia, et al.
(författare)
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Novel activity of acriflavine against colorectal cancer tumor cells
- 2011
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Ingår i: Cancer Science. - : Wiley. - 1347-9032 .- 1349-7006. ; 102:12, s. 2206-2213
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Tidskriftsartikel (refereegranskat)abstract
- A high-throughput screen of the cytotoxic activity of 2000 molecules from a commercial library in three human colon cancer cell lines and two normal cell types identified the acridine acriflavin to be a colorectal cancer (CRC) active drug. Acriflavine was active in cell spheroids, indicating good drug penetration and activity against hypoxic cells. In a validation step based on primary cultures of patient tumor cells, acriflavine was found to be more active against CRC than ovarian cancer and chronic lymphocytic leukemia. This contrasted to the activity pattern of the CRC active standard drugs 5-fluorouracil, irinotecan and oxaliplatin. Mechanistic studies indicated acriflavine to be a dual topoisomerase I and II inhibitor. In conclusion, the strategy used seems promising for identification of new diagnosis-specific cancer drugs.
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| 5. |
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| 6. |
- Johansson, Erik, et al.
(författare)
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Exogenous introduction of tissue inhibitor of metalloproteinase 2 reduces accelerated growth of TGF-β-disrupted diffuse-type gastric carcinoma.
- 2010
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Ingår i: Cancer science. - : Wiley. - 1349-7006 .- 1347-9032. ; 101:11, s. 2398-403
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Tidskriftsartikel (refereegranskat)abstract
- Diffuse-type gastric carcinoma is characterized by rapid progression and poor prognosis. High expression of transforming growth factor (TGF)-β and thick stromal fibrosis are observed in this type of gastric carcinoma. We have previously shown that disruption of TGF-β signaling via introduction of a dominant negative form of the TGF-β type II receptor (dnTβRII) into diffuse-type gastric cancer cell lines, including OCUM-2MLN, caused accelerated tumor growth through induction of tumor angiogenesis in vivo. In the present study, we show that TGF-β induces upregulation of expression of tissue inhibitor of metalloproteinase 2 (TIMP2) in the OCUM-2MLN cell line in vitro, and that expression of TIMP2 is repressed by dnTβRII expression in vivo. Transplantation of the OCUM-2MLN cells to nude mice exhibited accelerated tumor growth in response to dnTβRII expression, which was completely abolished when TIMP2 was coexpressed with dnTβRII. Although the blood vessel density of TIMP2-expressing tumors was only slightly decreased, the degree of hypoxia in tumor tissues was significantly increased and pericytes covering tumor vasculature were decreased by TIMP2 expression in OCUM-2MLN cells, suggesting that the function of tumor vasculatures was repressed by TIMP2 and consequently tumor growth was reduced. These findings provide evidence that one of the mechanisms of the increase in angiogenesis in diffuse-type gastric carcinoma is the downregulation of the anti-angiogenic protein TIMP2.
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| 7. |
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| 8. |
- Mathot, Lucy, et al.
(författare)
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Behavior of seeds and soil in the mechanism of metastasis : A deeper understanding
- 2012
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Ingår i: Cancer Science. - : Wiley. - 1347-9032 .- 1349-7006. ; 103:4, s. 626-631
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Forskningsöversikt (refereegranskat)abstract
- The so-called seed and soil hypothesis proposed by Stephen Paget in 1889 to explain the metastatic behavior of cancer cells and the homing of certain cancers to selected sites has been a well-recognized phenomenon for over a century. What advances have been made to increase our understanding of this phenomenon and what does it really implicate in terms of targets for therapy? (Cancer Sci 2012; 103: 626631)
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| 9. |
- Moustakas, Aristidis, et al.
(författare)
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Signaling networks guiding epithelial-mesenchymal transitions during embryogenesis and cancer progression
- 2007
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Ingår i: Cancer Science. - : Wiley. - 1347-9032 .- 1349-7006. ; 98:10, s. 1512-1520
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Forskningsöversikt (refereegranskat)abstract
- Epithelial–mesenchymal transition (EMT) describes the differentiation switch between polarized epithelial cells and contractile and motile mesenchymal cells, and facilitates cell movements and generation of new tissue types during embryogenesis. Many secreted polypeptides are implicated in the EMT process and their corresponding intracellular transduction pathways form highly interconnected networks. Transforming growth factor-β, Wnt, Notch and growth factors acting through tyrosine kinase receptors induce EMT and often act in a sequential manner. Such growth factors orchestrate the concerted regulation of an elaborate gene program and a complex protein network, needed for establishment of new mesenchymal phenotypes after disassembly of the main elements of epithelial architecture, such as desmosomes, as well as tight, adherens and gap junctions. EMT of tumor cells occurs during cancer progression and possibly generates cell types of the tumor stroma, such as cancer-associated myofibroblasts. EMT contributes to new tumor cell properties required for invasiveness and vascular intravasation during metastasis. Here we present some of the current mechanisms that mediate the process of EMT and discuss their relevance to cancer progression.
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| 10. |
- Wickström, Malin, et al.
(författare)
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Aminopeptidase N (CD13) as a target for cancer chemotherapy
- 2011
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Ingår i: Cancer Science. - : Wiley. - 1347-9032 .- 1349-7006. ; 102:3, s. 501-508
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Forskningsöversikt (refereegranskat)abstract
- The enzyme aminopeptidase N (APN, also known as CD13) is a Zn2+ dependent membrane-bound ectopeptidase that degrades preferentially proteins and peptides with a N-terminal neutral amino acid. Aminopeptidase N has been associated with the growth of different human cancers and suggested as a suitable target for anti-cancerous therapy. Different approaches have been used to develop new drugs directed to this target, including enzyme inhibitors as well as APN-targeted carrier constructs. This review discusses the prevalence and possible function of APN in malignant diseases, mainly solid tumors, as well as its “drugability” evaluated in preclinical in vivo models, and also provides a brief overview of current clinical trials focused on APN.
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