- Cancer Cells and Metastasis
- Chemokine receptors and signaling
- Cancer, Stress, Anesthesia, and Immune Response
- Cancer, Hypoxia, and Metabolism
- GDF15 and Related Biomarkers
- Epigenetics and DNA Methylation
- Peptidase Inhibition and Analysis
- Fibroblast Growth Factor Research
- Cancer Research and Treatments
- Macrophage Migration Inhibitory Factor
- Histone Deacetylase Inhibitors Research
- Genetic factors in colorectal cancer
- Nuclear Receptors and Signaling
- Colorectal Cancer Treatments and Studies
- Immune cells in cancer
- Protein Kinase Regulation and GTPase Signaling
- Liver physiology and pathology
- Inflammatory mediators and NSAID effects
- Immunotherapy and Immune Responses
- Melanoma and MAPK Pathways
- Nanoplatforms for cancer theranostics
- Hepatocellular Carcinoma Treatment and Prognosis
- Angiogenesis and VEGF in Cancer
- Cancer-related Molecular Pathways
- Gastric Cancer Management and Outcomes
Karolinska Institutet
2009-2023
Boehringer Ingelheim (Austria)
2023
Heidelberg University
2016-2017
German Cancer Research Center
2016-2017
Lund University
2010-2014
Jena University Hospital
2014
Linköping University
2012
Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine
2012
Uppsala University
2010-2012
National Chung Hsing University
2012
Selective irreversible inhibitors of selenoprotein TXNRD1 yield anticancer efficacy without overt systemic toxicity in mouse models.
This study explored the role of secreted fibroblast-derived factors in prostate cancer growth. Analyses matched normal and tumor tissue revealed up-regulation CXCL14 cancer-associated fibroblasts a majority cancer. Fibroblasts over-expressing promoted growth xenografts, increased angiogenesis macrophage infiltration. Mechanistic studies demonstrated that autocrine CXCL14-stimulation stimulate migration ERK-dependent proliferation fibroblasts. monocyte was also demonstrated. Furthermore,...
Platelet-derived growth factor (PDGF) receptor signaling is a major functional determinant of cancer-associated fibroblasts (CAF). Elevated expression PDGF receptors on stromal CAFs associated with metastasis and poor prognosis, but mechanism(s) that underlie these connections are not understood. Here, we report the identification secreted glycoprotein stanniocalcin-1 (STC1) as mediator by function in setting colorectal cancer. PDGF-stimulated increased migration invasion cocultured cancer...
Abstract Cancer-associated fibroblasts (CAF) stimulate tumor growth and metastasis. Signals supporting CAF function are thus emerging as candidate therapeutic targets in the microenvironment. The chemokine CXCL14 is a potent inducer of protumorigenic functions. This study aimed at learning how protumoral functions CXCL14-expressing maintained. We found that nitric oxide synthase NOS1 upregulated stimulated with CXCL14. Induction Nos1 was associated oxidative stress occurred together...
Abstract The tumor stroma is vital to development, progression, and metastasis. Cancer-associated fibroblasts (CAF) are among the abundant cell types in stroma, but range of their contributions cancer pathogenicity has yet be fully understood. Here, we report a critical role for upregulation TGFβ/BMP family member GDF15 (MIC-1) stroma. was found upregulated situ primary cultures CAF from prostate cancer. Ectopic expression produced prominent paracrine effects on migration, invasion, growth....
Physical activity is associated with reduced risk of several cancers, including aggressive prostate cancer. The mechanisms mediating the effects are not yet understood; among candidates modifications endogenous hormone levels. Long-term exercise known to reduce serum levels growth stimulating hormones. In contrast, endocrine acute endurance include increased mitogenic factors such as GH and IGF-1. It can be speculated that elevation may detrimental cancer progression into malignancy....
Drug resistance is a major problem in cancer therapy. A growing body of evidence demonstrates that the tumor microenvironment, including cancer-associated fibroblasts (CAFs), can modulate drug sensitivity cells. We examined effect primary human CAFs on p53 induction and cell viability prostate cells treatment with chemotherapeutic drugs. Co-culture or CAF-conditioned medium attenuated DNA damage response to drugs enhanced survival. inhibited accumulation doxorubicin, but not taxol, manner...
Abstract Purpose: Fibroblasts expressing the orphan chemokine CXCL14 have been previously shown to associate with poor breast cancer prognosis and promote growth. This study explores mechanism underlying survival associations of stromal CXCL14. Experimental Design: Tumor cell epithelial-to-mesenchymal transition (EMT), invasion, metastasis were studied in vitro vivo models together fibroblasts overexpressing An approach for receptor identification included loss-of-function studies followed...
Abstract Cancer-associated fibroblasts (CAFs) promote tumor growth and progression, increase drug resistance through several mechanisms. We have investigated the effect of CAFs on p53 response to doxorubicin in prostate cancer cells. show that produce interleukin-6 (IL-6), IL-6 attenuates induction upregulation pro-apoptotic target Bax upon treatment with doxorubicin. This is associated increased levels MDM2 mRNA, Mdm2 protein bound p53, ubiquitinated p53. also inhibited doxorubicin-induced...
The inhibitory reversible oxidation of protein tyrosine phosphatases (PTPs) is an important regulatory mechanism in growth factor signaling. Studies on PTP have focused pathways that increase or decrease reactive oxygen species levels and thereby affect oxidation. processes involved reactivation oxidized PTPs remain largely unknown. Here the role thioredoxin (Trx) system was analyzed using a combination vitro cell-based assays. Cells lacking major Trx reductase TrxR1 ( Txnrd1 −/− ) displayed...
Cancer-associated fibroblasts (CAF) attract increasing attention as potential cancer drug targets due to their ability stimulate, for example, tumor growth, invasion, angiogenesis, and metastasis. However, the molecular mechanisms causing tumor-promoting properties of CAFs remain poorly understood. Forkhead box F1 (FoxF1) is a mesenchymal target hedgehog signaling, known regulate mesenchymal-epithelial interactions during lung development. Studies with FoxF1 gain- loss-of-function revealed...
Expression of the chemokine CXCL14 has previously been shown to be elevated in tumour stroma of, for example, prostate and breast cancer. Cancer-associated fibroblast-derived enhances growth mouse models However, prognostic significance compartment-specific expression not studied.CXCL14 mRNA was analysed a cancer tissue microarray (TMA) formalin-fixed, paraffin-embedded tumours by RNAscope 2.0 Assay. Epithelial stromal separately correlated with clinicopathological characteristics...
Ras is a membrane-associated small G-protein that funnels growth and differentiation signals into downstream signal transduction pathways by cycling between an inactive, GDP-bound active, GTP-bound state. Aberrant activity as result of oncogenic mutations causes de novo cell transformation promotes tumor progression. Here, we describe novel strategy to block deregulated means oligomerized cognate protein modules derived from the Ras-binding domain c-Raf (RBD), which named MSOR for m...
Sorafenib, a multi-tyrosine kinase inhibitor, kills more effectively the non-metastatic prostate cancer cell line 22Rv1 than highly metastatic PC3. In cells, constitutively active STAT3 and ERK are targeted by sorafenib, contrasting with PC3 in which these kinases not active. Notably, overexpression of MEK construct cells stimulates sustained phosphorylation Bad protects from sorafenib-induced death. Src AKT activated leading to an increase Bim protein levels. Overexpression or knockdown...
Immune cells can regulate disease progression and response to treatment in multiple tumor types, but their activities human soft tissue sarcoma are poorly characterized.Marker-defined immune cell subsets were characterized from a microenvironmental perspective two independent cohorts of by multiplex IHC, quantitative PCR and/or bioinformatics.B profiling revealed prognostic role for CD20 protein (cohort 1, 33 patients) MS4A1 gene expression 2, 265 patients). Multiplex IHC correlation...
Tissue-specific markers are useful for identification of tumour type in advanced cancers unknown origin. This study investigated the expression glutamate decarboxylase 1 (GAD1) prostate and control tissue compared with established prostate-specific antigen (PSA) membrane (PSMA).A microarray was constructed 36 adenocarcinomas, eight benign samples malignant tissues from urinary bladder, lung rectum. Immunohistochemistry GAD1, PSA PSMA performed. The products staining intensity extent were...