Omentum-derived matrix enables the study of metastatic ovarian cancer and stromal cell functions in a physiologically relevant environment.

High-grade serous (HGS) ovarian cancer is the most lethal gynaecological disease in the world and metastases is a major cause. The omentum is the preferential metastatic site in HGS ovarian cancer patients and models that recapitulate the original environment of this organ at cellular and molecular level are being developed to study basic mechanisms that underpin this disease. The tumour extracellular matrix (ECM) plays active roles in HGS ovarian cancer pathology and response to therapy.

Randomized, double-blinded, placebo-controlled pilot study: efficacy of faecal microbiota transplantation on chronic fatigue syndrome.

Background: Chronic fatigue syndrome (CFS) is a disabling illness of unknown aetiology. Disruption of gut microbiota may play a role in several neurological disorders. In this study, the effect of faecal microbiota transplantation (FMT) on fatigue severity and health-related quality of life (HRQOL) in patients with CFS was evaluated.

Clozapine-Related Diarrhea and Colitis: Report of 4 Cases.

Background: During clozapine treatment, diarrhea is a rare but clinically relevant adverse effect. Cases of microscopic colitis and eosinophilic colitis have been previously reported.

Procedures: We present 4 patients who developed severe diarrhea in early weeks of clozapine therapy.

Blocking Angiopoietin-2 Promotes Vascular Damage and Growth Inhibition in Mouse Tumors Treated with Small Doses of Radiation.

Abnormal vasculature in tumors leads to poor tissue perfusion and cytostatic drug delivery. Although drugs inducing vascular normalization, for example, angiopoietin-2 (Ang2)-blocking antibodies, have shown promising results in preclinical tumor models, clinical studies have so far shown only little efficacy. Because Ang2 is known to play a protective role in stressed endothelial cells, we tested here whether Ang2 blocking could enhance radiation-induced tumor vascular damage.

Spa type distribution in MRSA and MSSA bacteremias and association of spa clonal complexes with the clinical characteristics of bacteremia.

The genetic distribution of invasive methicillin-susceptible (MSSA) and resistant S. aureus (MRSA) strains has to be addressed in order to target infection control strategies. A large MRSA epidemic caused by a certain MRSA strain (spa type 067) broke out in 2001 in our health district.

Comparison of outcome and clinical characteristics of bacteremia caused by methicillin-resistant, penicillin-resistant and penicillin-susceptible Staphylococcus aureus strains.

Background: The aim of this study was to assess the association of methicillin resistance and penicillinase production with clinical characteristics and outcome of Staphylococcus aureus bacteremia.

Methods: For 126 patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia, 378 age- and gender-matched controls with methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia were selected. Of controls, 126 had bacteremia caused by penicillin-susceptible strains (PSSA) and 252 by penicillinase-producing strains (PRSA).

Nrf2/Keap1 Pathway and Expression of Oxidative Stress Lesions 8-hydroxy-2'-deoxyguanosine and Nitrotyrosine in Melanoma.

Background/aim: Increased expression and prognostic significance of major redox regulator nuclear factor erythroid-2-related factor (Nrf2) is recognized in many cancers. Our aim was to investigate the role of oxidative stress markers in melanoma.

Materials And Methods: We characterized the immunohistochemical expression of Nrf2, kelch-like ECH-associated protein 1 (Keap1), BRAF(V600E), 8-hydroxy-2'-deoxyguanosine (8-OHdG) and nitrotyrosine in 36 nevi, 14 lentigo maligna and 71 malignant melanomas.

Combined interventions are effective in MRSA control.

Background: A large healthcare-associated epidemic mainly caused by one methicillin-resistant Staphylococcus aureus (MRSA) strain broke out in Pirkanmaa County, Finland, in 2001. This study describes the impact of infection control and screening practices on the epidemic.

Methods: The number of hospital-acquired (HA)-MRSA findings obtained from clinical and screening samples during the epidemic was calculated.

Bcl-xl and Mcl-1 are the major determinants of the apoptotic response to dual PI3K and MEK blockage.

The dual targeting of PI3K-AKT-mTOR and Ras-Raf-MEK-ERK pathways is a potential anticancer therapy, but unfortunately, the response rate has been low in early phase clinical trials. Pre-clinical models have suggested that an apoptotic response to dual PI3K and MEK targeting is relatively rare and understanding apoptotic avoidance could lead to increased clinical efficiency. This study investigated solid cancer cell lines, which are known to be sensitive to dual PI3K and MEK inhibition but to have a limited apoptotic response.

Combining targeted drugs to overcome and prevent resistance of solid cancers with some stem-like cell features.

Treatment resistance significantly inhibits the efficiency of targeted cancer therapies in drug-sensitive genotypes. In the current work, we studied mechanisms for rapidly occurring, adaptive resistance in targeted therapy-sensitive lung, breast, and melanoma cancer cell lines. The results show that in ALK translocated lung cancer lines H3122 and H2228, cells with cancer stem-like cell features characterized by high expression of cancer stem cell markers and/or in vivo tumorigenesis can mediate adaptive resistance to oncogene ablative therapy.

Alternative dosing of dual PI3K and MEK inhibition in cancer therapy.

Background: PI3K/AKT/mTOR and RAS/RAF/MEK/ERK pathways are thought to be the central transducers of oncogenic signals in solid malignancies, and there has been a lot of enthusiasm for developing inhibitors of these pathways for cancer therapy. Some preclinical models have suggested that combining inhibitors of both parallel pathways may be more efficacious, but it remains unknown whether dual inhibition with high enough concentrations of the drugs to achieve meaningful target inhibition is tolerable in a clinical setting. Furthermore, the predictive factors for dual inhibition are unknown.

A controlled register-based study of 460 neurofibromatosis 1 patients: increased fracture risk in children and adults over 41 years of age.

Neurofibromatosis 1 (NF1, von Recklinghausen's disease) is an autosomal dominant neurocutaneous-skeletal syndrome in which low bone mineral density (BMD) and osteoporosis are common. Low BMD is, however, not the sole component of fracture risk. In the current study, 460 Finnish patients with NF1 were identified from the hospital medical records and their fracture risk was evaluated.

A novel treatment strategy for EGFR mutant NSCLC with T790M-mediated acquired resistance.

The purpose of our study was to identify novel kinase inhibitors for the treatment of genetic subsets of non-small cell lung cancer (NSCLC). NSCLC cell lines (n = 8) with known oncogenic backgrounds (K-Ras, EGFR and EML4-ALK) were exposed to several kinase inhibitors and analyzed for cell growth/cytotoxicity and signaling. Gö6976, a classical protein kinase C inhibitor, showed high potency against mutated EGFR and was further validated in vitro using additional NSCLC lines (n = 4) and Ba/F3 models and in vivo using a xenograft model.

The development of cutaneous neurofibromas.

Cutaneous neurofibromas are the hallmarks of neurofibromatosis type 1 (NF1). They are composed of multiple cell types, and traditionally they are believed to arise from small nerve tributaries of the skin. A key finding in the context of this view has been that subpopulations of tumor Schwann cells harbor biallelic inactivation of the NF1 gene (NF1(-/-)).