Karl-henning Kalland - Academia.edu (original) (raw)

Papers by Karl-henning Kalland

XLS file 2928K, Changed gene expression in D5HS comparing to EPT2-D5 cells

Cancer Research, 2014

Background: The androgen receptor (AR) is activated and pathogenic in castration resistant prosta... more Background: The androgen receptor (AR) is activated and pathogenic in castration resistant prostate cancer (CRPC) due to a variety of escape mechanisms from anti-androgen treatment. The “cell of origin” of prostate cancer is not finally defined, but in different models prostate epithelial basal cells have been shown to develop into cancer with authentic prostate cancer features. The AR and target genes are effectively silenced in prostate epithelial basal cells. Given the importance of activated AR in prostate cancer we performed a reassessment of the basis of its silencing in prostate epithelial basal cells. Results: EP156T cells are derived from primary prostate epithelial basal cells and were propagated in monolayer cultures with features of transit amplifying cells in medium with low calcium concentration. The AR was not detectable in these cells and neither the AR nor target genes such as KLK3 (PSA), TMPRSS2 and NKX3-1 were induced following treatment with synthetic androgen (R...

Genes of cell-cell interactions, chemotherapy detoxification and apoptosis are induced during che... more Genes of cell-cell interactions, chemotherapy detoxification and apoptosis are induced during chemotherapy of acute myeloid leukemia

British journal of cancer, Feb 6, 2018

Despite successful implementation of drugs targeting the human epidermal growth factor receptor 2... more Despite successful implementation of drugs targeting the human epidermal growth factor receptor 2 (HER2) receptor in breast and gastric cancers, the potential of HER2 as a therapeutic target in other cancers has been less studied, including endometrial cancer. We investigated expression levels of HER2 (ERBB2) in a large cohort of endometrial cancer lesions, also including complex atypical hyperplasia and metastatic lesions. 67 precursor lesions, 790 primary endometrial cancers and 383 metastatic lesions were investigated for HER2 expression in relation to clinicopathologic features and outcome. Protein levels were assessed by immunohistochemistry (using the HercepTest and staining index (SI) criteria), mRNA levels by microarrays and amplification status by chromogenic in situ hybridisation. High HER2 protein levels were significantly associated with features of aggressive disease and increased mRNA ERBB2 levels. HER2 expression defined by the SI proved to be a better predictor of su...

Cancer Research, 2013

Background: p63 is a transcription factor that is central for epithelial homeostasis and developm... more Background: p63 is a transcription factor that is central for epithelial homeostasis and development. In our cell culture model of epithelial to mesenchymal transition (EMT) in a human prostate cells, p63 was one of the most down-regulated transcription factors during EMT. This led us to investigate the role of p63 in EMT by a gain and loss of function approach. Results: Over-expression of the predominant epithelial isoform ΔNp63α in mesenchymal EPT1 and EPT2 cells led to gain of several epithelial characteristics without resulting in a complete mesenchymal to epithelial transition (MET). When p63 was knocked down in epithelial EP156T cells complementary results were observed. Global gene expression analyses found that ΔNp63α induced gene modules involving cell adhesion genes in mesenchymal like cells. ChIP-seq analyses confirmed the enriched binding of p63 to regulatory areas of genes associated with cell adhesion in prostate epithelial cells. CDH1 and ZEB1 are two elemental factor...

International Journal of Oncology, 2005

Prostate carcinoma is the most common cancer of western men and is a markedly heterogeneous disea... more Prostate carcinoma is the most common cancer of western men and is a markedly heterogeneous disease. The aim of this study was to identify signatures of differentially expressed genes in prostate cancer using DNA microarray technology, evaluating expression profiles in matched pairs of benign and malignant tissue. Samples were collected from 33 radical prostatectomies, and 52 specimens were included, representing 29 histologically verified primary tumours, 19 paired samples of malignant and benign tissue, and 4 non-paired benign tissue samples. Microarray analysis was performed using an expanded sequence verified set of 40,000 human cDNA clones, revealing several genes with significant differences between malignant and benign tissue, including recently reported genes like alpha-methylacyl-CoA racemase (AMACR) and hepsin, as well as genes relevant for tumour development and progression. Leave out cross validation (LOCV) test correctly predicted tumour or benign tissue in 47 (90.3%) out of 52 cases, significantly better than cross validation tests using randomly permuted tissue labels. Unsupervised clustering analysis revealed 3 distinct patient clusters significantly associated with Gleason score, and high grade tumours (Gleason score &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;/=7) accumulated in cluster 1 (C1). Gene expression profiles correctly predicted 100% of tumour samples segregating to C1, as also validated by LOCV. Gene expression profiles were analysed in filtered and floored datasets with similar results, and a pair-wise design was also tested. Gene expression profiles provided tumour clusters linked to differentiation, and revealed novel markers relevant for molecular classification, grading and therapy of prostate cancer.

PLoS ONE, 2013

Chromosome 8q24 is the most commonly amplified region across multiple cancer types, and the typic... more Chromosome 8q24 is the most commonly amplified region across multiple cancer types, and the typical length of the amplification suggests that it may target additional genes to MYC. To explore the roles of the genes most frequently included in 8q24 amplifications, we analyzed the relation between copy number alterations and gene expression in three sets of endometrial cancers (N = 252); and in glioblastoma, ovarian, and breast cancers profiled by TCGA. Among the genes neighbouring MYC, expression of the bromodomain-containing gene ATAD2 was the most associated with amplification. Bromodomain-containing genes have been implicated as mediators of MYC transcriptional function, and indeed ATAD2 expression was more closely associated with expression of genes known to be upregulated by MYC than was MYC itself. Amplifications of 8q24, expression of genes downstream from MYC, and overexpression of ATAD2 predicted poor outcome and increased from primary to metastatic lesions. Knockdown of ATAD2 and MYC in seven endometrial and 21 breast cancer cell lines demonstrated that cell lines that were dependent on MYC also depended upon ATAD2. These same cell lines were also the most sensitive to the histone deacetylase (HDAC) inhibitor Trichostatin-A, consistent with prior studies identifying bromodomain-containing proteins as targets of inhibition by HDAC inhibitors. Our data indicate high ATAD2 expression is a marker of aggressive endometrial cancers, and suggest specific inhibitors of ATAD2 may have therapeutic utility in these and other MYC-dependent cancers.

PLoS ONE, 2012

Background: Despite being the most common pelvic gynecologic malignancy in industrialized countri... more Background: Despite being the most common pelvic gynecologic malignancy in industrialized countries, no targeted therapies are available for patients with metastatic endometrial carcinoma. In order to improve treatment, underlying molecular characteristics of primary and metastatic disease must be explored. Methodology/Principal Findings: We utilized the mass spectrometric-based mutation detection technology OncoMap to define the types and frequency of point somatic mutations in endometrial cancer. 67 primary tumors, 15 metastases corresponding to 7 of the included primary tumors and 11 endometrial cancer cell lines were screened for point mutations in 28 known oncogenes. We found that 27 (40.3%) of 67 primary tumors harbored one or more mutations with no increase in metastatic lesions. FGFR2, KRAS and PIK3CA were consistently the most frequently mutated genes in primary tumors, metastatic lesions and cell lines. Conclusions/Significance: Our results emphasize the potential for targeting FGFR2, KRAS and PIK3CA mutations in endometrial cancer for development of novel therapeutic strategies.

Molecular Cancer Research, 2014

The angiogenic switch, a rate-limiting step in tumor progression, has already occurred by the tim... more The angiogenic switch, a rate-limiting step in tumor progression, has already occurred by the time most human tumors are detectable. However, despite significant study of the mechanisms controlling this switch, the kinetics and reversibility of the process have not been explored. The stability of the angiogenic phenotype was examined using an established human liposarcoma xenograft model. Nonangiogenic cells inoculated into immunocompromised mice formed microscopic tumors that remained dormant for approximately 125 days (vs. <40 days for angiogenic cells) whereupon the vast majority (>95%) initiated angiogenic growth with second-order kinetics. These original, clonally derived angiogenic tumor cells were passaged through four in vivo cycles. At each cycle, a new set of single-cell clones was established from the most angiogenic clone and characterized for in vivo for tumorigenic activity. A total of 132 single-cell clones were tested in the second, third, and fourth in vivo pa...

Frontiers in Pharmacology

Our drug discovery model has identified two novel STAT3 SH2 domain inhibitors 323–1 and 323–2 (de... more Our drug discovery model has identified two novel STAT3 SH2 domain inhibitors 323–1 and 323–2 (delavatine A stereoisomers) in a series of experiments. In silico computational modeling, drug affinity responsive target stability (DARTS), and fluorescence polarization (FP) assays altogether determined that 323–1 and 323–2 directly target the STAT3 SH2 domain and inhibited both phosphorylated and non-phosphorylated STAT3 dimerization. Computational docking predicted that compound 323s bind to three subpockets of the STAT3 SH2 domain. The 323s inhibition of STAT3 dimerization was more potent than the commercial STAT3 SH2 domain inhibitor S3I-201 in the co-immunoprecipitation assay, correlating with computational docking data. The fluorescence polarization assay further confirmed that the compound 323s target the STAT3 SH2 domain by competitively abrogating the interaction between STAT3 and the SH2-binding peptide GpYLPQTV. Compared with S3I-201, the 323 compounds exhibited stronger inhib...

Authors' original file for figure 3

Tidsskrift for Den norske legeforening, 2021

Ein nestor i norsk virologi, tidlegare professor og overlege Gunnar Haukenes er gå bort. Han var ... more Ein nestor i norsk virologi, tidlegare professor og overlege Gunnar Haukenes er gå bort. Han var ein sympatisk og dyktig forelesar og forskar med stor kunnskap som kom mange til ny e.

Journal of Clinical Microbiology, 1988

Restriction endonuclease-generated polynucleotide and synthetically produced oligonucleotide gene... more Restriction endonuclease-generated polynucleotide and synthetically produced oligonucleotide gene probes used in colony hybridization assays proved to be efficient for the detection and differentiation of enterotoxigenic Escherichia coli. To compare their relative efficiencies, these two sets of probes were radiolabeled with 32P and were applied to 74 strains of E. coli with known enterotoxin profiles and to 156 previously unexamined E. coli isolates. The enterotoxigenic bacteria Vibrio cholerae O1, Vibrio cholerae non-O1 (NAG), Yersinia enterocolitica, and E. coli harboring the plasmid vectors of the polynucleotide gene probes were examined for further evaluation of probe specificity. The two classes of probes showed a perfect concordance in their specific detection and differentiation of enterotoxigenic E. coli. In the analysis of six strains, the signal strength on autoradiography after hybridization with oligonucleotides was weaker than that obtained after hybridization with pol...

Biomarkers of the Tumor Microenvironment, 2017

The Journal of Lipid Research, 2002

The non-␤-oxidisable tetradecylthioacetic acid (TTA) is incorporated into cellular membranes when... more The non-␤-oxidisable tetradecylthioacetic acid (TTA) is incorporated into cellular membranes when C3H/ 10T1/2 cells are cultured in TTA-containing medium. We here demonstrate that this alteration in cellular membranes affect the nuclear translocation of proteins involved in signal transduction. Analysis of cellular fatty acid composition shows that TTA and TTA:1n-8 constitute approximately 40 mol% of total fatty acids in cellular/nuclear membranes. Activation of c-fos expression is significantly inhibited in TTA-treated cells but the enzymatic activation of mitogen activated protein kinase (ERK) is not affected. Immunofluorescence and confocal microscopy studies demonstrate that in mitogene-stimulated TTA-treated cells, the translocation of phosphorylated ERK1/2, protein kinase C ␣ (PKC ␣), and PKC ␤ 1 from the cytoplasm into the nucleus is considerably decreased and delayed. Concomitant with a decreased nuclear import, ERK1/2 dephosphorylation is decreased in TTA-treated cells. There is no TTA-induced inhibition of nuclear import of proteins with a classical nuclear localization signal (NLS), as seen by in vitro nuclear import experiments of BSA fused to the NLS from SV40 large T, or in vivo studies of hnRNP A1 nuclear import. The expression levels of Importin ␣ , Importin ␤ , Importin 7, and NTF2 are not altered in the TTA-treated cells. Taken together, our data indicate that TTA treatment causes changes in cellular fatty acid composition that negatively affect NLS-independent mechanisms of protein translocation through the nuclear pore complex.-Bjørndal, B.

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Tidsskrift for den Norske lægeforening : tidsskrift for praktisk medicin, ny række, Jan 20, 1987

Immunohistochemical staining of various clock proteins in urothelial cancer as compared to normal... more Immunohistochemical staining of various clock proteins in urothelial cancer as compared to normal controls stained in parallel. Counterstained with hematoxylin (blue nuclei). Magnification is given by the tool bar: 10 Îźm. A: PER1 in tumour showing the same staining density as in controls (B). C: PER3 with positive nuclei in tumour as compared to negative in the controls (D). The cytoplasm is slightly positive in both. E: CRY1 with increased positivity in tumour cell cytoplasm as compared to the control (F). G: CRY2 with negative reaction in tumour cell nuclei and positive in controls (H). I: BMAL-1 with approximately equal staining in tumour cells and control (J), i.e. moderate staining in nuclei and strong in cytoplasm. For semi quantitative estimates and details, see Table 3. (PDF 617 kb)

Expression of stem cell markers and angiogenic factors in GBM xenografs. A-T) Immunostaining agai... more Expression of stem cell markers and angiogenic factors in GBM xenografs. A-T) Immunostaining against the markers (green) indicated in left panels. Sections are also stained for the pan human specific marker HuNu (red). Nuclear counterstaining: DAPI (blue). Left panels: Low magnification (×10 a, b and d, ×20 c, e and k-o) showing the tumour bulk and periphery. The tumour cell nuclei appear violet due to red HuNu and blue counterstaining. Right panels: High magnification (×80 f-j and p-t, and inserts y160 f-j and p-t) of the tumour bed. Scale bars: left panels 100 μm (a-e and k-o), right panels 25 μm (f-j and p-t) and inserts 5 μm (f-j and p-t). (JPG 3534 kb)

MRI, H/E and flow cytometry of non-angiogenic and mature GBM phenotypes. A) Upper panels: MRI of ... more MRI, H/E and flow cytometry of non-angiogenic and mature GBM phenotypes. A) Upper panels: MRI of non-angiogenic tumour. Contrast-enhanced T1 sequence (left) shows no enhancement. T2 (right) shows a diffuse lesion (red arrowhead). Lower panels: MRI of mature GBM phenotype. Contrasted T1 (left) shows enhancement (white arrowhead) due to leaky tumour vessels and dark areas of necrosis (red arrowhead). T2 (right) shows the tumour lesion. B) H/E staining of nonangiogenic (upper) and mature GBM tumours (lower). Non-angiogenic tumour with infiltrative growth (left) and cellular atypia (right). The mature GBM phenotype displays shift of midline structures (lower, left panel) and enlarged vessels, necrotic regions (white arrowhead) and pseudopalisading cells (red arrowhead) surrounded by dilated vessels (black arrowhead, lower right panel). Scale bars: left and right panels 100 μm. C) Scatter plot of the cell suspension: gating for live cells (left), gating by APC (CD11b and CD31) and GFP (r...