- Keywords
- Viscoat, Healon, Hyal-2000,
- MeSH
- Biomedical and Dental Materials classification MeSH
- Chondroitin Sulfates therapeutic use MeSH
- Cataract Extraction methods MeSH
- Cohort Studies MeSH
- Hyaluronic Acid analogs & derivatives therapeutic use MeSH
- Humans MeSH
- Endothelium, Corneal surgery injuries MeSH
- Check Tag
- Humans MeSH
- Keywords
- stereotaktická biopsie,
- MeSH
- Biopsy, Needle methods MeSH
- Humans MeSH
- Brain Neoplasms diagnosis MeSH
- Neuronavigation MeSH
- Stereotaxic Techniques MeSH
- Check Tag
- Humans MeSH
- MeSH
- Algorithms MeSH
- Financing, Organized MeSH
- Humans MeSH
- Fetus MeSH
- Image Processing, Computer-Assisted MeSH
- Statistics as Topic methods MeSH
- Ultrasonography, Prenatal methods instrumentation utilization MeSH
- Image Enhancement methods MeSH
- Imaging, Three-Dimensional methods instrumentation MeSH
- Check Tag
- Humans MeSH
Rationale: Despite growing evidence for mitochondria's involvement in cancer, the roles of specific metabolic components outside the respiratory complex have been little explored. We conducted metabolomic studies on mitochondrial DNA (mtDNA)-deficient (ρ0) cancer cells with lower proliferation rates to clarify the undefined roles of mitochondria in cancer growth. Methods and results: Despite extensive metabolic downregulation, ρ0 cells exhibited high glycerol-3-phosphate (G3P) level, due to low activity of mitochondrial glycerol-3-phosphate dehydrogenase (GPD2). Knockout (KO) of GPD2 resulted in cell growth suppression as well as inhibition of tumor progression in vivo. Surprisingly, this was unrelated to the conventional bioenergetic function of GPD2. Instead, multi-omics results suggested major changes in ether lipid metabolism, for which GPD2 provides dihydroxyacetone phosphate (DHAP) in ether lipid biosynthesis. GPD2 KO cells exhibited significantly lower ether lipid level, and their slower growth was rescued by supplementation of a DHAP precursor or ether lipids. Mechanistically, ether lipid metabolism was associated with Akt pathway, and the downregulation of Akt/mTORC1 pathway due to GPD2 KO was rescued by DHAP supplementation. Conclusion: Overall, the GPD2-ether lipid-Akt axis is newly described for the control of cancer growth. DHAP supply, a non-bioenergetic process, may constitute an important role of mitochondria in cancer.
- MeSH
- Energy Metabolism MeSH
- Ethers metabolism MeSH
- Glycerolphosphate Dehydrogenase * genetics metabolism MeSH
- Humans MeSH
- Mitochondria * enzymology MeSH
- Mice MeSH
- Neoplasms * enzymology pathology MeSH
- Proto-Oncogene Proteins c-akt * metabolism MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Distension is a regular mechanical stimulus in gastrointestinal (GI) tract. This study was designed to investigate the effect of hypotonic stress on pacemaking activity and determine whether actin microfilament is involved in its mechanism in cultured murine intestinal interstitial cells of Cajal (ICCs) by using whole-cell patch-clamp and calcium imaging techniques. Hypotonic stress induced sustained inward holding current from the baseline to -650+/-110 pA and significantly decreased amplitudes of pacemaker current. Hypotonic stress increased the intensity of basal fluorescence ratio (F/F0) from baseline to 1.09+/-0.03 and significantly increased Ca(2+) oscillation amplitude. Cytochalasin-B (20 microM), a disruptor of actin microfilaments, significantly suppressed the amplitudes of pacemaker currents and calcium oscillations, respectively. Cytochalasin-B also blocked hypotonic stress-induced sustained inward holding current and hypotonic stress-induced increase of calcium oscillations. Phalloidin (20 microM), a stabilizer of actin microfilaments, significantly enhanced the amplitudes of pacemaker currents and calcium oscillations, respectively. Despite the presence of phalloidin, hypotonic stress was still able to induce an inward holding current and increased the basal fluorescence intensity. These results suggest that hypotonic stress induces sustained inward holding current via actin microfilaments and the process is mediated by alteration of intracellular basal calcium concentration and calcium oscillation in cultured intestinal ICCs.
- MeSH
- Biological Clocks physiology MeSH
- Mechanotransduction, Cellular physiology MeSH
- Gastrointestinal Motility physiology MeSH
- Cells, Cultured MeSH
- Actin Cytoskeleton metabolism MeSH
- Mice, Inbred BALB C MeSH
- Mice MeSH
- Osmotic Pressure physiology MeSH
- Telocytes physiology MeSH
- Calcium Signaling physiology MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Mice MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
BACKGROUND: HannaH (NCT00950300) was a phase III, randomized, international, open-label study that compared pharmacokinetics (PK), efficacy, and safety of two different trastuzumab formulations [subcutaneous (s.c.) and intravenous (i.v.)] in HER2-positive, operable, locally advanced, or inflammatory breast cancer in the neoadjuvant/adjuvant setting. The co-primary end points, to show noninferiority of s.c. versus i.v. trastuzumab in terms of serum concentration (Ctrough) and pathologic complete response (pCR) were met; safety profiles were comparable at 12 months' median follow-up. Secondary end points included safety and tolerability, PK profile, immunogenicity, and event-free survival (EFS). We now report updated safety and efficacy data after a median follow-up of 20 months. PATIENTS AND METHODS: Patients (N = 596) were treated with eight cycles of neoadjuvant chemotherapy, administered concurrently with 3-weekly s.c. trastuzumab (fixed dose of 600 mg) or the standard weight-based i.v. method. Following surgery, patients continued trastuzumab treatment to complete 1 year of therapy. Updated analyses of PK, efficacy, safety, and immunogenicity data were carried out. RESULTS: s.c. trastuzumab was generally well tolerated and the incidence of adverse events (AEs), including grade 3 or 4 AEs, between treatment groups was comparable. A slightly higher incidence of serious AEs (SAEs), mainly due to infections, was reported with s.c. treatment {64 [21.5%; 95% confidence interval (CI) 17.0%-26.7%] versus 42 (14.1%; 95% CI 10.4%-18.6%) in the i.v. group}; however, the differences were small and often based on rare events, with no observable pattern across reported events. An early analysis of EFS showed rates of 95% in both groups 1 year postrandomization. Exploratory analyses did not reveal an association between toxicity and body weight or exposure. CONCLUSIONS: Overall, the safety profile of s.c. trastuzumab was consistent with the previously published data from HannaH and the known safety profile of i.v. trastuzumab. EFS rates were comparable between the i.v. and s.c. groups. CLINICAL TRIAL NUMBER: NCT00950300.
- MeSH
- Antineoplastic Agents administration & dosage adverse effects pharmacokinetics MeSH
- Adult MeSH
- Injections, Subcutaneous MeSH
- Infusions, Intravenous MeSH
- Middle Aged MeSH
- Humans MeSH
- Breast Neoplasms drug therapy genetics MeSH
- Receptor, ErbB-2 biosynthesis genetics MeSH
- Trastuzumab administration & dosage adverse effects MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial, Phase III MeSH
- Research Support, Non-U.S. Gov't MeSH
- Randomized Controlled Trial MeSH
Remifentanil is a commonly used opioid in anesthesia with cardioprotective effect in ischemia-reperfused (I/R) heart. We evaluated the influence of remifentanil on myocardial infarct size and expressions of proteins involved in apoptosis in I/R rat heart following various time protocols of remifentanil administration. Artificially ventilated anesthetized Sprague-Dawley rats were subjected to a 30 min of left anterior descending coronary artery occlusion followed by 2 h of reperfusion. Rats were randomly assigned to one of five groups; Sham, I/R only, remifentanil preconditioning, postconditioning and continuous infusion group. Myocardial infarct size, the phosphorylation of ERK1/2, Bcl2, Bax and cytochrome c and the expression of genes influencing Ca2+ homeostasis were assessed. In remifentanil-administered rat hearts, regardless of the timing and duration of administration, infarct size was consistently reduced compared to I/R only rats. Remifentanil improved expression of ERK 1/2 and anti-apoptotic protein Bcl2, and expression of sarcoplasmic reticulum genes which were significantly reduced in the I/R rats only. Remifentanil reduced expression of pro-apoptotic protein, Bax and cytochrome c. These suggested that remifentanil produced cardioprotective effect by preserving the expression of proteins involved in anti-apoptotic pathways, and the expression of sarcoplasmic reticulum genes in I/R rat heart, regardless of the timing of administration.
- MeSH
- Adjuvants, Anesthesia MeSH
- Apoptosis drug effects MeSH
- Time Factors MeSH
- Cytochromes c metabolism MeSH
- Financing, Organized MeSH
- Phosphorylation MeSH
- Hemodynamics drug effects MeSH
- Homeostasis MeSH
- Myocardial Infarction MeSH
- Rats MeSH
- RNA, Messenger metabolism MeSH
- Mitogen-Activated Protein Kinase 1 metabolism MeSH
- Mitogen-Activated Protein Kinase 3 metabolism MeSH
- Disease Models, Animal MeSH
- Myocardium metabolism pathology MeSH
- Piperidines administration & dosage pharmacology MeSH
- Reverse Transcriptase Polymerase Chain Reaction MeSH
- Rats, Sprague-Dawley MeSH
- bcl-2-Associated X Protein metabolism MeSH
- Proto-Oncogene Proteins c-bcl-2 metabolism MeSH
- Gene Expression Regulation drug effects MeSH
- Myocardial Reperfusion MeSH
- Sarcoplasmic Reticulum metabolism MeSH
- Calcium metabolism MeSH
- Cell Survival drug effects MeSH
- Blotting, Western MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
Článek je věnován nedávno zesnulým, významným postavám psychoterapie a zejména rodinné terapie, které položily základy specifických terapeutických přístupů a přispěly k rozvoji těchto oblastí poznání. Uvedeny jsou hlavní předpoklady a myšlenky čtyř osobností psychoterapie ve vztahu k rozvoji tzv. psychopatologie, roli terapeuta a terapeutickému procesu. Uvedeny jsou též některé kritické připomínky k přístupům, jež zmíněné osobnosti vytvořily.
The article is devoted to recently deceased, respected figures of psychotherapy and particularly family therapy, who layed the foundations for specific approaches and thus contributed to the development of the abovementioned disciplines. Main assumptions and ideas of those influential figures regarding psychopathology, a therapist´s role and therapeutic process are overviewed including some critical comments towards approaches that those therapists developed.
- MeSH
- Algorithms MeSH
- Diagnostic Imaging methods instrumentation utilization MeSH
- Financing, Organized MeSH
- Humans MeSH
- Fetus physiology MeSH
- Pattern Recognition, Automated methods utilization MeSH
- Statistics as Topic MeSH
- Cheek physiology MeSH
- Ultrasonography, Prenatal methods instrumentation utilization MeSH
- Imaging, Three-Dimensional methods instrumentation utilization MeSH
- Check Tag
- Humans MeSH
