| 1. |
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| 2. |
- Ekerljung, Lina, et al.
(författare)
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Effects of HER2-binding affibody molecules on intracellular signaling pathways
- 2006
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Ingår i: Tumor Biology. - : Springer Science and Business Media LLC. - 1010-4283 .- 1423-0380. ; 27:4, s. 201-210
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: HER2, which is overexpressed in 25-30% of human breast cancers, is a tyrosine kinase receptor critical for the signal transduction network that regulates proliferation, migration and apoptosis of cells. METHOD: We report the effects of two novel HER2-binding affibody molecules (Affibody), (ZHER2:4)2 and ZHER2:342, on intracellular signal transduction pathways (Erk1/2, Akt and PLCgamma1) using quantitative immunoblotting techniques and their biological effects in cell culture. The clinically approved antibody trastuzumab (Herceptin) was used as reference substance. RESULTS: Our data showed that, although all substances target HER2, the effects on the receptor and signaling molecules differed. For example, HER2 phosphorylation was induced by trastuzumab and (ZHER2:4)2 but inhibited by ZHER2:342. The effects these substances had on signal transduction correlated to some degree with changes in growth and migration, e.g. (ZHER2:4)2 stimulated phosphorylation of Erk1/2 and PLCgamma1, as well as growth and migration, while ZHER2:342 did not. ZHER2:342 even inhibited phosphorylation of PLCgamma1 and migration. CONCLUSION: Our data suggest that ZHER2:342 is a promising small agent (7 kDa) that may be used as an alternative, or complement, to trastuzumab. If radiolabelled, it can hopefully also be used for HER2 imaging and radionuclide therapy.
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| 6. |
- Håkansson, Joakim, 1975, et al.
(författare)
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Neural cell adhesion molecule-deficient beta-cell tumorigenesis results in diminished extracellular matrix molecule expression and tumour cell-matrix adhesion
- 2005
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Ingår i: Tumour Biology. - : Springer Science and Business Media LLC. - 1010-4283 .- 1423-0380. ; 26:2, s. 103-112
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Tidskriftsartikel (refereegranskat)abstract
- To understand by which mechanism neural cell adhesion molecule (N-CAM) limits beta tumour cell disaggregation and dissemination, we searched for potential downstream genes of N-CAM during beta tumour cell progression by gene expression profiling. Here, we show that N-CAM-deficient beta-cell tumorigenesis is associated with changes in the expression of genes involved in cell-matrix adhesion and cytoskeletal dynamics, biological processes known to affect the invasive and metastatic behaviour of tumour cells. The extracellular matrix (ECM) molecules emerged as the primary target, i.e. N-CAM deficiency resulted in down-regulated mRNA expression of a broad range of ECM molecules. Consistent with this result, deficient deposition of major ECM stromal components, such as fibronectin, laminin 1 and collagen IV, was observed. Moreover, N-CAM-deficient tumour cells displayed defective matrix adhesion. These results offer a potential mechanism for tumour cell disaggregation during N-CAM-deficient beta tumour cell progression. Prospective consequences of these findings for the role of N-CAM in beta tumour cell dissemination are discussed.
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| 7. |
- Jenndahl, Lachmi E, et al.
(författare)
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Characterization of integrin and anchorage dependence in mammary epithelial cells following c-erbB2-induced epithelial-mesenchymal transition.
- 2006
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Ingår i: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine. - : Springer Science and Business Media LLC. - 1010-4283. ; 27:1, s. 50-8
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Tidskriftsartikel (refereegranskat)abstract
- Signalling from the proto-oncogene c-erbB2 in mammary epithelial cells has earlier been shown to result in epithelial-mesenchymal transition (EMT) giving rise to fibroblast-like cells, and acquisition of anchorage-independent growth (AIG) usually determined by growth capacity in soft agar. In this study, we have analysed AIG associated with c-erbB2-induced EMT in a human mammary epithelial cell line. Intriguingly, cells capable of growth in soft agar were shown to be dependent on the function of beta(1) integrin extracellular matrix receptors for growth in collagen. We therefore tested the hypothesis that apparent AIG was due to deposition of extracellular matrix in the agar. Although the fibroblastic cells had strongly upregulated expression of the fibronectin receptor subunit integrin alpha(5) andabundant fibronectin fibrils, these properties did not have a positive correlation with AIG. Furthermore, antibody blocking of integrin alpha(5) and beta(1) failed to inhibit AIG. These results indicate that the anchorage-independent cells are not dependent on connection to extracellular matrix, but instead may be subject to a growth-inhibitory effect from the collagen in the absence of integrin signalling. This notion was supported by the finding that integrin blocking of the fibroblastic cells in fibrin was without effect on proliferation.
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| 8. |
- Langenskiöld, Marcus, 1972, et al.
(författare)
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Differential Prognostic Impact of uPA and PAI-1 in Colon and Rectal Cancer.
- 2009
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Ingår i: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine. - : Springer Science and Business Media LLC. - 1423-0380. ; 30:4, s. 210-220
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Tidskriftsartikel (refereegranskat)abstract
- Background and Objectives: Degradation of extracellular matrix is important for tumour growth and invasion, which in part is regulated by the plasminogen activation system. The aim of the study was to evaluate the protein expression of urokinase plasminogen activator (uPA) and plasminogen-activating inhibitor-1 (PAI-1) in plasma, tumour-free mucosa and tumour tissue regarding their prognostic value in colon and rectal cancer. Methods: Patients (n = 221) undergoing surgery for colorectal cancer were prospectively included. Samples were assayed by ELISA technique. Results: PAI-1 in tumour tissue (p = 0.006), plasma (<0.0001) and uPA in tumour-free mucosa (p = 0.006) were associated with survival in rectal cancer in univariate analysis. An uPA expression level below 1.1 ng/mg (log rank test, p < 0.0001) in tumour-free mucosa was associated with poor survival in rectal cancer. This was true also for patients without disseminated disease (M(0), p = 0.02). PAI-1 in plasma correlated with metastatic disease (p < 0.0001). uPA and PAI-1 were not associated with survival in either tumour tissue, mucosa or plasma in patients with colon cancer. Conclusions: uPA and PAI-1 have a differential prognostic impact in colon and rectal cancer. Preoperative mucosal uPA and plasma PAI-1 protein expression could possibly be used as prognostic factors in rectal cancer.
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| 9. |
- Linder, S
(författare)
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Cytokeratin markers come of age
- 2007
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Ingår i: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine. - : Springer Science and Business Media LLC. - 1010-4283. ; 28:4, s. 189-195
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Tidskriftsartikel (refereegranskat)
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| 10. |
- Liu, Minghui, et al.
(författare)
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Expression and function of vinculin in neuroendocrine tumors
- 2007
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Ingår i: Tumor Biology. - : Springer Science and Business Media LLC. - 1010-4283 .- 1423-0380. ; 28:4, s. 196-204
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Tidskriftsartikel (refereegranskat)abstract
- Transfection of chicken vinculin into highly malignant neuroendocrine tumor cells, vasostatin-transformed (vaso-transformed) Bon cells which expressed low levels of vinculin protein, reversed their malignant behavior and restored expression of tumor suppressor genes. Conversely, small interfering RNA (siRNA)-mediated knockout of vinculin resulted in fast cell growth and augmentation of colony formation in wild-type cells. Moreover, expression of a tight junction protein, claudin 4 (CLD4), was found to be associated with vinculin expression. In the vaso-transformed Bon cells, CLD4 expression was reduced, whereas a significantly increased CLD4 expression was observed in the cells with vinculin overexpression. Furthermore, vinculin knockout brought about CLD4 downregulation in wild-type cells. However, vinculin and CLD4 expression was inversely correlated in neuroendocrine tumors, respectively. Based on these findings, we hypothesize that vinculin plays a role in growth regulation of neuroendocrine tumors. Further studies are necessary to analyze the relationship between the course of the disease, and vinculin and CLD4 expression in large tumor samples.
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| 11. |
- Narisawa, S, et al.
(författare)
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Conserved epitopes in human and mouse tissue-nonspecific alkaline phosphatase - Second report of the ISOBM TD-9 Workshop
- 2005
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Ingår i: Tumor Biology. - : Springer Science and Business Media LLC. - 1010-4283 .- 1423-0380. ; 26:3, s. 113-120
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Tidskriftsartikel (refereegranskat)abstract
- A panel of 19 monoclonal antibodies (MAbs) against human tissue-nonspecific (liver/bone/kidney) alkaline phosphatase (TNAP) was obtained through the ISOBM TD-9 workshop. In the present study, the reactivity of these MAbs has been characterized against mouse TNAP. A mouse embryonic stem cell line, frozen sections of long bones, alkaline phosphatase extracted from mouse bone, and serum were used as the source of TNAP for individual assays. Each MAb was tested for immunoreactivity to mouse TNAP by Western blot analysis, immunohistochemistry and enzyme immunoassay. Antibodies 314 and 315 reacted strongly with mouse TNAP in Western blots, while all other antibodies were negative. By immunohistochemistry, antibodies 314, 315 and 333 produced strong positive staining using frozen sections, while antibody 334 was moderately positive. Enzyme immunoassays indicated that MAb 333 was also able to bind to serum TNAP. These antibodies represent very useful reagents to study the pathophysiological expression of TNAP in mouse tissues and in mouse serum. Copyright (C) 2005 S. Karger AG, Basel.
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| 13. |
- Nestor, Marika, et al.
(författare)
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Quantification of CD44v6 and EGFR expression in head and neck squamous cell carcinomas using a single-dose radioimmunoassay
- 2007
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Ingår i: Tumor Biology. - : Springer Science and Business Media LLC. - 1010-4283 .- 1423-0380. ; 28:5, s. 253-263
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Tidskriftsartikel (refereegranskat)abstract
- Background: In the growing field of tumor targeting, there is an urgent need to profile suitable molecular targets. In this study, CD44v6 and EGFR expression was quantified in samples of patients with head and neck squamous cell carcinoma (HNSCC) using a single-dose (SD) radioimmunoassay. Methods: The SD radioimmunoassay using 125I-chimeric monoclonal antibody (cMAb) U36 and 125I-cMAb cetuximab was first validated and then applied to quantify the expression of their target antigen molecules, CD44v6 and EGFR, in patient samples. Results were compared to immunohistochemical staining. Results: The SD assay provided sensitive quantitative values of the molecular targets studied, generally agreeing with the immunohistochemistry (IHC) results. The results indicated that expression of CD44v6 (0.2-20 nmol/μg membrane) was generally higher than that of EGFR (0.6-2.3 nmol/μg membrane) in the tumor samples analyzed, which corresponded to an average of 700,000 and 90,000 antigen molecules per cell, respectively. Conclusions: The SD radioimmunoassay is simple, reliable, and can be performed on a small amount (50 mg) of tissue. This assay could be a useful tool in the growing field of personalized cancer therapy, and can be used as a complement to IHC. In the tumors studied, CD44v6 was generally expressed at a higher level than EGFR, which might suggest that it could be more readily targeted by MAbs.
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| 14. |
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| 15. |
- Papworth, Karin, 1964-, et al.
(författare)
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Expression of erythropoietin and its receptor in human renal cell carcinoma
- 2009
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Ingår i: Tumor Biology. - : Springer Science and Business Media LLC. - 1010-4283 .- 1423-0380. ; 30:2, s. 86-92
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate the prognostic impact of erythropoietin (EPO) and EPO-receptor (EPO-R) expression in tumour as well as serum EPO in patients with renal cell carcinoma (RCC). Methods: Using immunohistochemistry, EPO and EPO-R were assessed in tissue microarrays from 195 RCCs. RCC type, TNM stage, nuclear grade, survival, EPO and haemoglobin (Hb) levels in blood were registered. Results: Strong expression of EPO and EPO-R in tumour tissue was found in 83 and 56%, respectively. EPO and EPO-R expression differed between RCC types. Serum EPO and blood Hb did not correlate to the expression of EPO or EPO-R. A positive correlation was found between the expression of EPO and EPO-R (p = 0.028). Survival was not related to tumour EPO, whereas strong EPO-R expression indicated a non-significantly worse prognosis. Serum EPO correlated positively to TNM stage and nuclear grade and negatively to survival. A multivariate analysis showed that TNM stage and nuclear grade were independent prognostic factors. Tumour EPO and EPO-R expression as well as serum EPO added no independent prognostic information. Conclusion: No correlation between EPO or EPO-R in tumour tissue and serum EPO or blood Hb was found. Neither EPO, EPO-R in tumour tissue nor serum EPO are independent prognostic factors.
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| 16. |
- Papworth, Karin, 1964-, et al.
(författare)
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Parathyroid hormone-related protein and serum calcium in patients with renal cell carcinoma
- 2005
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Ingår i: Tumor Biology. - : Springer Science and Business Media LLC. - 1010-4283 .- 1423-0380. ; 26:4, s. 201-206
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To evaluate serum parathyroid hormone-related protein (PTHrP) in relation to serum calcium and clinical outcome of patients with renal cell carcinoma. Methods: Sera from 243 patients with renal cell carcinoma were collected prior to therapy. Serum PTHrP was analyzed using an immunoradiometric assay. Tumour stage, nuclear grade, corrected serum calcium, and survival were assessed. Results: Serum PTHrP was detectable in 37/243 sera (15%) and hypercalcaemia (≥2.60 mmol/l) in 32/220 (15%). A positive correlation between serum PTHrP and serum calcium was found (r = 0.326; p < 0.01). Following subdivision of the material, based on storage time, the frequency of detectable serum PTHrP seemed to decrease with time. Serum calcium, but not serum PTHrP, was correlated to tumour stage (p < 0.001). Survival was similar for patients with detectable and undetectable PTHrP, but those with hypercalcaemia had a significantly shorter survival time compared to those with normal serum calcium (p < 0.001). A multivariate analysis showed that tumour stage and serum calcium were independent prognostic factors, but not grade or PTHrP. Conclusions: A positive relation of serum PTHrP to serum calcium was demonstrated in patients with renal cell carcinoma. Hypercalcaemia but not serum PTHrP predicted a worse prognosis.
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| 17. |
- Persson, Jonas, et al.
(författare)
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Molecular evolution of specific human antibody against MUC1 mucin results in improved recognition of the antigen on tumor cells.
- 2009
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Ingår i: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine. - : Springer Science and Business Media LLC. - 1423-0380 .- 1010-4283. ; 30:4, s. 221-31
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Tidskriftsartikel (refereegranskat)abstract
- The MUC1 mucin is differentially expressed and glycosylated in cancer tissue as opposed to healthy tissue. Due to these differences, MUC1 is considered a potential biomarker suitable for cancer diagnosis and therapy. In a previous study, the human MUC1-specific antibody 12ESC-6 was able to bind a sequence variant of the tandem repeat of MUC1 that is not recognized by many other MUC1-specific antibodies. It was also found to bind efficiently to MUC1-carrying cells. We have now used 12ESC-6 as starting point for random mutagenesis to isolate variants with improved ability to bind MUC1 in human tumor tissue. The resulting 12ESC-6 variants were shown to recognize not only the naked MUC1 tandem repeat but even more so glycosylated variants thereof, in particular those carrying the GalNAc (Tn) glycoform. Selected variants of 12ESC-6 demonstrated improved staining of MUC1 on cell lines using flow cytometry and improved staining of the antigen in breast tumor tissue by immunohistochemistry. Molecular evolution and specific fine-tuning thus have the potential to improve the performance of antibody specificities targeting tumor-associated epitopes on MUC1 mucin.
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| 20. |
- Sandström, Karl, et al.
(författare)
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Targeting CD44v6 expressed in head and neck squamous cell carcinoma : preclinical characterization of an 111In-labeled monoclonal antibody
- 2008
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Ingår i: Tumor Biology. - : Springer Science and Business Media LLC. - 1010-4283 .- 1423-0380. ; 29:3, s. 137-144
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Tidskriftsartikel (refereegranskat)abstract
- In patients with head and neck squamous cell carcinoma (HNSCC) radioimmunodiagnosis could offer a more specific and sensitive tumor diagnostic method.Our aim was to evaluate the labeling and biodistribution of the novel radioimmunoconjugate (111)In-cMAb U36. In this study cMAb U36, targeting CD44v6, and huA33, as a negative control, were labeled with indium-111, using the chelator CHXA''-DTPA. Immunoreactivity assays and binding studies were performed in vitro. Biodistribution and tumor imaging were conducted after intravenous injection of the radioimmunoconjugate to nude mice bearing HNSCC xenografts expressing CD44v6. The immunoreactive fraction was very high and the binding was CD44v6-specific. In vivo results demonstrated a promising biodistribution, with tumors clearly accumulating radioactivity with time. At 168 h postinjection (p.i.) the tumor uptake was 54.7 +/- 16.6% injected dose/g. The cMAb U36 had significantly (p < 0.05) higher uptake in tumors 72 h p.i. compared to huA33. We produced a novel radioimmunoconjugate targeting CD44v6 for possible use in the detection of HNSCC. The conjugate demonstrates no adverse effects from labeling and a favorable biodistribution.
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| 21. |
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| 22. |
- Zhang, Zhi-Yong, et al.
(författare)
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Nup88 expression in normal mucosa, adenoma, primary adenocarcinoma and lymph node metastasis in the colorectum
- 2007
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Ingår i: Tumor Biology. - : Springer Science and Business Media LLC. - 1010-4283 .- 1423-0380. ; 28:2, s. 93-99
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: It was the aim of this study to investigate Nup88 expression in normal colorectal mucosa, adenoma, adenocarcinoma and lymph node metastasis, as well as the relationship between Nup88 expression and clinicopathological features. Methods: Nup88 expression was examined by immunohistochemistry in 84 normal mucosa samples, 32 adenomas, 181 primary adenocarcinomas, and 18 lymph node metastases from colorectal tumour patients. Results: Nup88 expression was observed in normal epithelial and tumour cells. The frequency of strong Nup88 expression was increased from normal mucosa or adenoma to primary tumour and lymph node metastasis (p < 0.0001). There was no significant difference in the expression between normal mucosa and adenoma (p = 0.41). The frequency of strong Nup88 expression was higher in ulcerated tumours (40%) than in polypoid/large fungating tumours (23%, p = 0.048). The frequency of strong Nup88 expression was significantly different among tumours with good (21%), moderate (42%) and poor differentiation (48%, p = 0.01). Nup88 expression was not related to the patients' gender, age, tumour location, size, histological type, invasive depth, lymph node status and Dukes stage (p > 0.05). Conclusion: Our results suggest that Nup88 may play a role during the development, aggressiveness and differentiation of colorectal tumours. Copyright © 2007 S. Karger AG.
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