
Leif Andersson- University of Helsinki
Leif Andersson
- University of Helsinki
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Publications (439)
Low oxygen tension (PO 2 ), characterizes the tissue environment of tumors. The colorectal tumor line Colo205, grown under reduced oxygen tension expresses a novel αDβ1 integrin, which forms a cell surface complex with hemoglobin δ. This resulted in high local affinity for oxygen, which increased cell adhesion as compared with cells grown under nor...
Commentary on: Abadie V et al. IL‐15, gluten and HLA‐DQ8 drive tissue destruction in coeliac disease. Nature. 2020; 578: 600‐604 .
We investigated the associations between periodontal inflammation (gingivitis and periodontitis) and all-kind malignancies, specifically breast and prostate cancer, in a cohort followed-up for 30 years. The study hypothesis was based on the oral inflammation vs. systemic health paradigm. A sample of 2,168 subjects from an original cohort of 105,718...
Hyperpolarization-activated cyclic nucleotide-gated channels (HCN channels) are involved in spontaneous activity in many electrically active cell types such as cardiomyocytes and neurons. In this study, the role of HCN channels in proliferation and migration of Nestin and Sox2 expressing embryonic neural progenitor cells (NPC) originating from the...
Stanniocalcin-1 (STC-1) is a glycoprotein hormone involved in diverse biological processes, including regulation of calcium phosphate homeostasis, cell proliferation, apoptosis, inflammation, oxidative stress responses, and cancer development. The role of STC-1 in endometrial cancer (EC) is yet to be elucidated. In this study, we investigated the p...
Background
Colon cancer (CC) is one of the most commonly diagnosed malignancies worldwide. Several biomarkers have been suggested for improved prognostic evaluation, but few have been implemented in clinical practice. There is a need for biomarkers that predict the tumor behavior in CC and allow stratification of patients that would benefit from ad...
In humans, orthohantaviruses can cause hemorrhagic fever with renal syndrome (HFRS) or hantavirus pulmonary syndrome (HPS). An earlier study reported that acute Andes virus HPS caused a massive and transient elevation in the number of circulating plasmablasts with specificity towards both viral and host antigens suggestive of polyclonal B cell acti...
Mixed neuroendocrine-non-neuroendocrine neoplasms (MINEN) are rare tumors that consist of at least 30% of both neuroendocrine and non-neuroendocrine components. The data concerning pathogenesis of MINEN suggest a monoclonal origin. We describe a spontaneously immortalized cell line derived from gastric MINEN called GNEN-1. Primary tumor consisted o...
Aim
The key regulator of the polyamine biosynthetic pathway is ornithine decarboxylase (ODC). ODC is activated by antizyme inhibitor 1 (AZIN1) and 2 (AZIN2). AZIN1 and recently AZIN2 have been related to cancer, however, their functions in adenoid cystic carcinoma (ACC) have not been studied. We evaluated the immunoexpression of AZIN1 and 2 in tumo...
Simple Summary
In mammals, different diseases are associated with intestinal changes that may cause an increase in gut permeability. Intestinal permeability tests allow the evaluation of intestinal damage in humans, veterinary patients and laboratory animal models. When used in mouse models, these tests require that animals are singly housed in met...
Astroprincin (APCN, FAM171A1) is a recently characterized transmembrane glycoprotein that is abundant in brain astrocytes and is overexpressed in some tumors. However, the expression and role of APCN is unknown in oral tongue squamous cell carcinoma (OTSCC). Aim of this study was to investigate the expression of APCN in OTSCC tissue samples and to...
CD63, a member of the tetraspanin family, is expressed in endosomes and enriched in exosomes. Tetraspanins participate in a variety of physiological processes, including cellular differentiation, cell-cell fusion, and cell migration. CD63 reportedly carries both protumorigenic and tumor suppressor properties, and appears to be upregulated in breast...
Background & aims:
Celiac disease could be treated, and potentially cured, by restoring T-cell tolerance to gliadin. We investigated the safety and efficacy of negatively charged, 500 nm, poly(lactide-co-glycolide) nanoparticles encapsulating gliadin protein (TIMP-GLIA) in 3 mouse models of celiac disease. Uptake of these nanoparticles by antigen-...
Self-renewing neural stem cells and progenitor cells are cell populations that generate radial glial cells and neurons through asymmetric division. Regulation of intracellular pH in stem cells with high metabolic activity is critical for both cell signaling and proliferation. We have recently found that a S0859-inhibitable electrogenic Na/HCO3 co-t...
A stroke causes a hypoxic brain microenvironment that alters neural cell metabolism resulting in cell membrane hyperpolarization and intracellular acidosis. We studied how intracellular pH (pH i ) is regulated in differentiated mouse neural progenitor cells during hyperpolarizing conditions, induced by prompt reduction of the extracellular K ⁺ conc...
Ornithine decarboxylase (ODC) is the rate-limiting enzyme of polyamine synthesis. The two ODC antizyme inhibitors (AZIN1) and (AZIN2) are regulators of the catalytic activity of ODC. While AZIN1 is a regulator of cell proliferation, AZIN2 is involved in intracellular vesicle transport and secretion. There are no previous reports on the impact of AZ...
Treatment of A549 and LS174T cells with TGFβ+TNFα for three days induces EMT morphology (a) and elevated expression of AZIN2 (b). Loss of E-cadherin was seen in A549 cells (b).
(TIFF)
Induction of EMT by TGFβ and TNFα in different cell lines and effect on protein expression.
(DOCX)
Our group originally found and cloned cDNA for a 98-kDa type 1 transmembrane glycoprotein of unknown function. Because of its abundant expression in astrocytes, it was called the protein astroprincin (APCN). Two thirds of the evolutionarily conserved protein is intracytoplasmic, whereas the extracellular domain carries two N-glycosidic side chains....
Myxoinflammatory fibroblastic sarcoma is a soft-tissue neoplasm most frequently found in the distal extremities of middle-aged adults. Most myxoinflammatory fibroblastic sarcoma are low-grade tumors with propensity for local recurrence after incomplete removal. We report a myxoinflammatory fibroblastic sarcoma which developed in the foot of a 41-ye...
Expression of regenerating islet-derived protein 4 (REG4), a secretory protein involved in cell differentiation and proliferation, is upregulated in inflammatory bowel diseases and in many gastrointestinal malignancies. The prognostic significance of its expression in pancreatic ductal adenocarcinoma is unknown. Our aim was to investigate tumor tis...
The case-fatality rate of hantavirus disease depends strongly on the causative hantavirus, ranging from 0.1% to 40%. However, the pathogenesis is not fully understood and at present no licensed therapies exist. We describe fatal cases caused by Puumala hantavirus indicating involvement of complement activation and vascular leakage.
We investigated serum and saliva concentrations of matrix metalloproteinases, MMP-8, MMP-9, and MMP-13, and their tissue inhibitor TIMP-1, in a group of patients with and without periodontitis from Sweden. The hypothesis was that these biomarkers are higher in the periodontitis patients. Ninety patients participated in this cross-sectional study. F...
The objective of this study was to investigate whether there is an association between the amount of dental plaques and incidence of prostate cancer inpatients followed up for 28 years. We hypothesized that dental plaque reflects infection andaffects carcinogenesis via the inflammation pathway. This was a database incidencestudy on 83830-40-year-ol...
We have investigated and characterized a novel ornithine decarboxylase-related protein (ODCrp) also annotated as gm853. ODCrp shows 41% amino acid sequence identity with ODC and 38% with ODC antizyme inhibitor 1 (AZIN1). The Odcrp gene is selectively expressed in the epithelium of proximal tubuli of mouse kidney with higher expression in males than...
Stanniocalcin-1 (STC-1) is a nerve cell-enriched protein involved in intracellular calcium homeostasis regulation. Changes in calcium regulation are hypothesized to play a role in the pathophysiology of Alzheimer’s disease (AD). The expression of STC-1 increases in response to ischemic stroke, but whether it is altered in neurodegenerative disorder...
Hepatoblastoma, the most common type of pediatric liver cancer, is treated with a combination of surgery and chemotherapy. An essential drug in the treatment of hepatoblastoma is doxorubicin, which in high doses is cardiotoxic. This adverse effect is due to downregulation of cardiac expression of transcription factor GATA4, leading in turn to dimin...
Ornithine decarboxylase (ODC) antizyme inhibitor 2 (AZIN2), originally called ODCp, is a regulator of polyamine synthesis that we originally identified and cloned. High expression of ODCp mRNA was found in brain and testis. We reported that AZIN2 is involved in regulation of cellular vesicle transport and / or secretion, but the ultimate physiologi...
Significance
During the last decades, heart failure has developed into a major burden in the western world, increasingly affecting millions. Cardiac hypertrophy is an adaptive response to myocardial infarction or increased blood pressure, and it often leads to heart failure. Understanding the underlying regulatory processes in the development of pa...
Effects of triclosan (5-chloro-2′-(2,4-dichlorophenoxy)phenol) on mammalian cells were investigated using human peripheral blood mono nuclear cells (PBMC), keratinocytes (HaCaT), porcine spermatozoa and kidney tubular epithelial cells (PK-15), murine pancreatic islets (MIN-6) and neuroblastoma cells (MNA) as targets. We show that triclosan (1–10 μg...
Amylosin, a heat-stable channel-forming non-ribosomally synthesized peptide toxin produced by strains of Bacillus amyloliquefaciens isolated from moisture-damaged buildings, is shown in this paper to have immunotoxic and cytotoxic effects on human cells as well as antagonistic effects on microbes. Human macrophages exposed to 50 ng of amylosin ml(-...
We investigated statistical association between gingival inflammation and cancer in a group of patients followed up for 26 years with the hypothesis that gingival inflammation affects carcinogenesis. Altogether, 1676 30- to 40-year-old subjects from Stockholm were clinically examined in 1985. In 2011, we compared the baseline oral examination and f...
Introduction
Colorectal cancer (CRC) is one of the world’s three most common cancers and its incidence is rising. To identify patients who benefit from adjuvant therapy requires novel biomarkers. The regenerating islet-derived gene (REG) 4 belongs to a group of small secretory proteins involved in cell proliferation and regeneration. Its up-regulat...
Unlabelled:
The current treatment for celiac disease is strict gluten-free diet. Technical processing may render gluten-containing foods safe for consumption by celiac patients, but so far in vivo safety testing can only be performed on patients. We modified a celiac disease mouse model to test antigenicity and inflammatory effects of germinated r...
Background: Infections of teeth are highly prevalent, often leading to tooth extractions. Missing teeth can thus be considered as proxy for chronic dental infections, caries or periodontitis. We followed-up a cohort for 24 years investigating the association between missing teeth and the incidence of cancer with the hypothesis that dental chronic i...
DNA damage response (DDR) pathways have been extensively studied in cancer cell lines and mouse models, but little is known about how DNA damage is recognized by different cell types in nonmalignant, slowly replicating human tissues. Here, we assess, using ex vivo cultures of human prostate tissue, DDR caused by cytotoxic drugs (camptothecin, doxor...
We investigated statistical association between long-term periodontal disease and cancer in a group of patients followed-up for 24 years with the hypothesis that chronic infection affects carcinogenesis. We made a prospective study of 1676 30-40-year old subjects in Stockholm, clinically examined in 1985. The data were combined with Swedish Cancer...
We induced upregulation of stanniocalcin-1 (STC-1) by various mild and long lasting stresses and assayed its influence on mitochondrial membrane potential (MMP) in the neural crest-derived cell line Paju. The obtained data showed that starvation (24-96h), exposure to 10nM TPA, and low concentrations (0.05-1μM) of As2O3 significantly (3-5 times) upr...
Bacillus cereus, aseptically isolated from potato tubers, were screened for cereulide production and for toxicity on human and other mammalian
cells. The cereulide-producing isolates grew slowly, the colonies remained small (∼1 mm), tested negative for starch hydrolysis,
and varied in productivity from 1 to 100 ng of cereulide mg (wet weight)−1 (∼0...
Objectives:
Bacteria may play a role in oncogenesis (Chang & Parsonnet, Clin Microbiol Rev 2010;23:837). Infections of teeth are highly prevalent, often leading to tooth extractions. Missing teeth can thus be considered as proxy for chronic dental infections. We followed-up a cohort for 24 years investigating the association between missing teeth...
Reg IV is a 17kD secreted C-type lectin physiologically found in selected enteroendocrine cells (EEC). It is thought be involved in the regulation of normal and pathological intestinal and/or neuroendocrine differentiation and proliferation but its ultimate functional role(s) is still unclear. We used immunostaining and compared the cellular expres...
Breast cancer can recur even decades after the primary therapy. Markers are needed to predict cancer progression and the risk of late recurrence. The estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER2), proliferation marker Ki-67, and cytokeratin CK5 were studied to find out whether their expression o...
Stanniocalcin 1 (STC1), originally described as an antihypercalcemic hormone in fish, is highly expressed in differentiated mammalian neurons. Mild hypoxic treatment and focal cerebral ischemia induce upregulation of STC1 in the brain. These findings prompted us to investigate whether STC1 contributes to neuroprotection after ischemia and whether S...
Objectives: To study whether the amount of dental plaque, which indicates poor oral hygiene and is potential source of oral infections, associates with premature death in the chronic infection – carcinogenesis paradigm.
Methods: In a prospective cohort study, 1390 randomly selected healthy young Swedes followed up from 1985 to 2009.
All subject...
Prostate and seminal vesicle are two similar hormone responsive human organs that differ dramatically in their cancer incidence. DNA damage response (DDR) is required for maintenance of genomic integrity.
In this study we investigated the DDR and cell cycle checkpoint activation of these organs using orthotopic cultures of human surgery-derived tis...
Bmx (Bone marrow kinase in chromosome X), also known as Etk, is a member of the Tec family of nonreceptor tyrosine kinases. Bmx is expressed mainly in arterial endothelia and in myeloid hematopoietic cells. Bmx regulates ischemia-mediated arteriogenesis and lymphangiogenesis, but its role in tumor angiogenesis is not known. In this study, we charac...
To study whether the amount of dental plaque, which indicates poor oral hygiene and is potential source of oral infections, associates with premature death from cancer.
Prospective cohort study.
1390 randomly selected healthy young Swedes followed up from 1985 to 2009. All subjects underwent oral clinical examination and answered a questionnaire as...
Stanniocalcin 2 (STC2) is a homolog of stanniocalcin 1, a 56kD glycoprotein hormone that originally was found to confer calcitonin-like activity in fish. Human STC2 is expressed in various tissues such as kidney, spleen, heart, and pancreas. STC2 has been demonstrated to be induced by different kinds of stress and display cytoprotective activity, b...
DNA damage response (DDR) pathways have been extensively studied in cancer cell lines and mouse models, but little is known about how DNA damage is recognized by different cell types in nonmalignant, slowly replicating human tissues. Here, we assess, using ex vivo cultures of human prostate tissue, DDR caused by cytotoxic drugs (camptothecin, doxor...
PROX1 is a specific target of the β-catenin/TCF pathway in the intestinal epithelium. It acts as a regulator of progression from a benign to a highly dysplastic phenotype in colorectal tumours. However, the clinical significance of PROX1 expression is not known.
We studied the prognostic value of immunohistochemical expression of PROX1 in a series...
Twinfilins are evolutionarily conserved regulators of cytoskeletal dynamics. They inhibit actin polymerization by binding both actin monomers and filament barbed ends. Inactivation of the single twinfilin gene from budding yeast and fruit fly results in defects in endocytosis, cell migration, and organization of the cortical actin filament structur...
Transcription factor GATA-4 is expressed in early fetal liver and essential for organogenesis. It is also implicated in carcinogenesis in several endoderm-derived organs. Hepatoblastoma (HB), the most common malignant pediatric liver tumor, has features of fetal liver including extramedullary hematopoiesis. We investigated the expression of GATA-4...
We describe here comprehensive multi-layered genomic, molecular, functional and drug-sensitivity profiles of cancer specimens for clinical diagnostic and therapeutic use. A clinically and histologically atypical metastatic bone tumor was studied with the intent to inform clinicians in real time, should actionable findings emerge. This represents a...
Hemin (iron protoporphyrin IX) is a necessary component of many proteins, functioning either as a cofactor or an intracellular messenger. Hemoproteins have diverse functions, such as transportation of gases, gas detection, chemical catalysis and electron transfer. Stanniocalcin 1 (STC1) is a protein involved in respiratory responses of the cell but...
Breast cancer is known for its propensity to recur decades after treatment. The biology behind the phenomenon of tumor dormancy is still poorly understood. Bmi-1, c-myc, and Snail are transcription factors that have prognostic roles in several malignancies. In order to reveal whether any of these markers has impact on late relapses, we used immunoh...
The dissemination of tumor cells (metastasis) from the primary tumor is the principal cause of death in cancer patients. The lymphatic vessels serve as a key conduit for metastasizing tumor cells, which often colonize the lymph nodes first. Although the primary tumor and lymph nodes invaded by tumor cells are removed during surgery, tumor cells ins...
In addition to circulation, where it transfers phospholipids between lipoprotein particles, phospholipid transfer protein (PLTP) was also identified as a component of normal tear fluid. The purpose of this study was to clarify the secretion route of tear fluid PLTP and elucidate possible interactions between PLTP and other tear fluid proteins. Huma...
Detection of recurrent somatic rearrangements routinely allows monitoring of residual disease burden in leukemias, but is not used for most solid tumors. However, next-generation sequencing now allows rapid identification of patient-specific rearrangements in solid tumors. We mapped genomic rearrangements in three cancers and showed that PCR assays...
Vascular endothelial growth factor-B (VEGF-B) binds to VEGF receptor-1 and neuropilin-1 and is abundantly expressed in the heart, skeletal muscle, and brown fat. The biological function of VEGF-B is incompletely understood.
Unlike placenta growth factor, which binds to the same receptors, adeno-associated viral delivery of VEGF-B to mouse skeletal...
The main purpose was to evaluate the association between periodontal disease and the incidence of breast cancer in a prospective study of 3273 randomly selected subjects aged 30-40 years at baseline. Breast cancer incidence was registered from 1985 to 2001 according to the WHO International Classification of Diseases criteria. At baseline, 1676 ind...
DNA damage response (DDR) pathways have been extensively studied in cancer cell lines and mouse models, but little is known about how DNA damage is recognized by different cell types in nonmalignant, slowly replicating human tissues. Here, we assess, using ex vivo cultures of human prostate tissue, DDR caused by cytotoxic drugs (camptothecin, doxor...
At 2 years of age, 100% (23/23) of ERbeta(-/-) female mice have developed large pituitary and ovarian tumors. The pituitary tumors are gonadotropin-positive and the ovarian tumors are sex cord (less differentiated) and granulosa cell tumors (differentiated and estrogen secreting). No male mice had pituitary tumors and no pituitary or ovarian tumors...
Antizyme inhibitor 1 (AZIN1) and 2 (AZIN2) are proteins that activate ornithine decarboxylase (ODC), the key enzyme of polyamine biosynthesis. Both AZINs release ODC from its inactive complex with antizyme (AZ), leading to formation of the catalytically active ODC. The ubiquitously expressed AZIN1 is involved in cell proliferation and transformatio...
Reg IV (RELP), a Regenerating protein family member, is constitutively expressed in neuroendocrine cells of the intestinal mucosa. The helix-loop-helix transcription factor Hath1 is the human homologue of murine Math1, which regulates the embryonic differentiation of neural and intestinal secretory lineage cells. Hath1 is constitutively expressed i...
: We investigated the expression and functional characteristics of β-adrenoceptors in a panel of 10 phenotypically different human hematopoietic cell lines. A binding assay with [125I]iodocyanopindolol as the ligand revealed that cell lines of myelomonocytic or histiocytic derivation (HL-60, ML-2, RC-2A, U-937) expressed high numbers of β-adrenocep...
We studied the effects of toxins, which inhibited the motility of boar spermatozoa, on rat liver mitochondria. The toxins studied were originally from bacteria isolated from moisture-damaged buildings where inhabitants exhibited symptoms, or from food causing poisoning. Some strains of Bacillus cereus and Streptomyces griseus produced potassium ion...
High activity of ornithine decarboxylase (ODC), the rate-limiting enzyme of polyamine synthesis, is typically present in rapidly proliferating normal and malignant cells. The mitotically inactive steroidogenic cells in rodent testis and ovaries, however, also display high ODC activity. The activity of ODC in these cells responds to luteinizing horm...
Polyamines are small cationic molecules that in adult brain are connected to neuronal signaling by regulating inward-rectifier K+-channels and different glutamate receptors. Antizyme inhibitors (AZINs) regulate the cellular uptake of polyamines and activate ornithine decarboxylase (ODC), the rate-limiting enzyme of polyamine synthesis. Elevated lev...
The carbohydrate structures of cellular glycoconjugates in normal, hyperplastic, adenomatous and carcinomatous human colorectal mucosa were analysed with six fluorescein isothiocyanate-conjugated lectins. In normal, hyperplastic and adenomatous colorectal mucosa showing mild or moderate dysplasia Concanavalin A (Con A), Lens culinaris (LCA), and wh...
Resting and activated DBA/2 T and non-T spleen lymphocytes were compared with a view to their ability to stimulate CBA spleen T lymphocytes in one-way mixed lymphocyte culture. Resting T and non-T cells were obtained by fractionation of spleen lymphocytes in preparative free flow cell electrophoresis. Activated T and non-T cells were obtained by st...
Maspin is a serine protease inhibitor with tumor suppressor activity. Maspin can suppress tumor growth and metastasis in vivo and tumor cell motility and invasion in vitro. Maspin also modulates apoptosis of tumor cells, possibly by modulating the expression of the B-cell lymphoma-2 family member. p53 regulates the expression of the tumor suppresso...
Transforming growth factor beta 1 (TGF-beta1) promotes epithelial healing in inflammatory bowel disease. We hypothesized that GATA-4, a transcription factor cooperating with TGF-beta signaling pathway, is upregulated by TGF-beta1 in the inflamed intestinal epithelium.
Normal and inflamed intestinal samples were subjected to immunohistochemistry for...
Both polymorphonuclear (PMN) and mononuclear (MN) leucocytes constitute targets for glucocorticoid hormones. In order to comparatively characterize the earliest steps of steroid action in these cell populations, we investigated the concentrations and specificities of glucocorticoid receptors in purified human PMNs and MNs by a whole-cell binding as...
L3 morphology according to the FAB classification and the 14q+ chromosome are usually ascribed to the Burkitt type of leukaemia or lymphoma with a B or pre-B cell phenotype. We report here a case of adult acute leukaemia with Burkitt morphology and the 14q+, which did not express lymphoid markers. Instead, the leukaemia was shown to be an acute ery...
Ornithine decarboxylase (ODC) is the rate-limiting enzyme of polyamine synthesis. Polyamines and ODC are connected to cell proliferation and transformation. Resting cells display a low ODC activity while normal, proliferating cells display fluctuations in ODC activity that coincide with changes in the actin cytoskeleton during the cell cycle. Cance...
With specific liver X receptor alpha and beta (LXRalpha and LXRbeta) antibodies, we found that LXRalpha is strongly expressed in the luminal and basal cells of prostatic epithelium. The ventral prostates (VP) of LXRalpha(-/-) mice are characterized by the presence of smooth-muscle actin-positive stromal overgrowth around the prostatic ducts and by...
Upon IgE-mediated activation, mast cells (MC) exocytose their cytoplasmic secretory granules and release a variety of bioactive substances that trigger inflammatory responses. Polyamines mediate numerous cellular and physiological functions. We report here that MCs express antizyme inhibitor 2 (AZIN2), an activator of polyamine biosynthesis, previo...
Background Transforming growth factor beta 1 (TGF-β1) promotes epithelial healing in inflammatory bowel disease. We hypothesized that
GATA-4, a transcription factor cooperating with TGF-β signaling pathway, is upregulated by TGF-β1 in the inflamed intestinal
epithelium.
Methods Normal and inflamed intestinal samples were subjected to immunohistoch...
Vascular endothelial growth factor (VEGF)-B is poorly angiogenic but prominently expressed in metabolically highly active tissues, including the heart. We produced mice expressing a cardiac-specific VEGF-B transgene via the alpha-myosin heavy chain promoter. Surprisingly, the hearts of the VEGF-B transgenic mice showed concentric cardiac hypertroph...
Breast cancer is known for its propensity to recur even after decades. The biology behind this phenomenon of tumor dormancy is poorly understood. The stanniocalcins (stanniocalcin-1, STC-1 and stanniocalcin-2, STC-2) are 56kDa homodimeric proteins. They act as pro-survival factors and contribute to the endurance of terminally differentiated cells s...
The Drosophila transcription factor Prospero functions as a tumor suppressor, and it has been suggested that the human counterpart of Prospero, PROX1, acts similarly in human cancers. However, we show here that PROX1 promotes dysplasia in colonic adenomas and colorectal cancer progression. PROX1 expression marks the transition from benign colon ade...
Hantaviruses are globally important human pathogens that cause hemorrhagic fever with renal syndrome and hantavirus pulmonary syndrome. Capillary leakage is central to hantaviral diseases, but how it develops, has remained unknown. It has been hypothesized that the pathogenesis of hantavirus infection would be a complex interplay between direct vir...
Human gastrointestinal mucosa regenerates vigorously throughout life, but the factors controlling cell fate in mature mucosa are poorly understood. GATA transcription factors direct cell proliferation and differentiation in many organs, and are implicated in tumorigenesis. GATA-4 and GATA-6 are considered crucial for the formation of murine gastroi...
ODC (ornithine decarboxylase), the rate-limiting enzyme in polyamine biosynthesis, is regulated by specific inhibitors, AZs (antizymes), which in turn are inhibited by AZI (AZ inhibitor). We originally identified and cloned the cDNA for a novel human ODC-like protein called ODCp (ODC paralogue). Since ODCp was devoid of ODC catalytic activity, we p...
Animals exposed for a few hours to low oxygen content (8%) develop resistance against further ischemic myocardial damage. The molecular mechanism(s) behind this phenomenon, known as hypoxic preconditioning (HOPC), is still incompletely understood. Stanniocalcin-1 (STC-1) is an evolutionarily conserved glycoprotein originally discovered in fish, in...
Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract. The tumors characteristically harbor KIT or PDGFRA mutations, and mutant tumors respond to imatinib mesylate (Glivectrade mark). Chromosomal imbalances resulting in altered gene dosage are known to have a role in the molecular pathogenesis of t...
Cellular DNA damage triggers the DNA damage response pathway and leads to enforcement of cell cycle checkpoints, which are essential for the maintenance of genomic integrity and are activated in early stages of tumorigenesis. A special feature of prostate cancer is its high incidence and multifocality. To address the functionality of DNA damage che...
Exposure of animals for a few hours to moderate hypoxia confers relative protection against subsequent ischemic brain damage. This phenomenon, known as hypoxic preconditioning, depends on new RNA and protein synthesis, but its molecular mechanisms are poorly understood. Increased expression of IL-6 is evident, particularly in the lungs of animals s...