Search results for "small"
showing 10 items of 2441 documents
Treatment of Stage III-IV Non-Small-Cell Lung Carcinoma with Vinorelbine in Combination with Ifosfamide plus MESNA: A Study by the Southern Italy Onc…
1996
Thirty-five patients affected by stage III-IV non-small-cell lung carcinomas were treated with ifosfamide 3 gr/m2 plus MESNA as uroprotector on day 1 and vinorelbine 25 mg/m2 i.v. bolus on day 1 and 8. This cycle was repeated every 21 days. Over a total of 35 evaluable patients, the overall response rate was 34% (95% CL 18-54%). One patient experienced a complete response with a duration of 7.2+ months, and 11 patients a partial response with a mean duration of 5.9+ months. Seven patients had no change and 16 improved. The overall survival was 7.6+ months. Over a total of 145 cycles, the most frequent toxicity was myelosuppression, but grade 3 leukopenia and grade 2 thrombocytopenia were se…
Small interfering RNA (siRNA) inhibits the expression of the Her2/neu gene, upregulates HLA class I and induces apoptosis of Her2/neu positive tumor …
2003
Silencing of a specific mRNA using double stranded RNA oligonucleotides represents one of the newest technologies for suppressing a specific gene product. Small interfering RNA (siRNA) are 21 nucleotides long, double stranded RNA fragments that are identical in sequence to the target mRNA. We designed 3 such siRNA against the Her2/neu (HER2) gene. The HER2 gene is known to play an important role in the oncogenesis of several types of cancers, such as breast, ovarian, colon and gastric cancers. Introduction of the siRNA into HER2 positive tumor lines in vitro greatly reduced the cell surface expression of the HER2 protein. Concurrently, a range of effects on cell physiology, such as growth i…
A phase Ib/II study of HER3-targeting lumretuzumab in combination with carboplatin and paclitaxel as first-line treatment in patients with advanced o…
2019
Purpose This study investigated the safety and clinical activity of lumretuzumab, a humanised antihuman epidermal growth factor receptor 3 (HER3) monoclonal antibody, in combination with carboplatin and paclitaxel in first-line treatment of patients with squamous non-small cell lung cancer (sqNSCLC). HER3 ligand heregulin and HER3 protein expression were evaluated as potential biomarkers of clinical activity. Patients and methods This open-label, phase Ib/II study enrolled patients receiving lumretuzumab at 800 mg (flat) in combination with carboplatin (area under the curve (AUC) 6 mg/mL×min) and paclitaxel (200 mg/m 2) administered intravenously on a every 3-week schedule. Adverse event (A…
Rad51 and BRCA2 - New Molecular Targets for Sensitizing Glioma Cells to Alkylating Anticancer Drugs
2011
First line chemotherapeutics for brain tumors (malignant gliomas) are alkylating agents such as temozolomide and nimustine. Despite growing knowledge of how these agents work, patients suffering from this malignancy still face a dismal prognosis. Alkylating agents target DNA, forming the killing lesion O(6)-alkylguanine, which is converted into DNA double-strand breaks (DSBs) that trigger apoptosis. Here we assessed whether inhibiting repair of DSBs by homologous recombination (HR) or non-homologous end joining (NHEJ) is a reasonable strategy for sensitizing glioma cells to alkylating agents. For down-regulation of HR in glioma cells, we used an interference RNA (iRNA) approach targeting Ra…
Carbon based nanomaterials for the detection of narrow therapeutic index pharmaceuticals
2020
Precise detection of important pharmaceuticals with narrow therapeutic index (NTI) is very critical as there is a small window between their effective dose and the doses at which the adverse reactions are very likely to appear. Regarding the fact that various pharmacokinetics will be plausible while considering pharmacogenetic factors and also differences between generic and brand name drugs, accurate detection of NTI will be more important. Current routine analytical techniques suffer from many drawbacks while using novel biosensors can bring up many advantages including fast detection, accuracy, low cost with simple and repeatable measurements. Recently the well-known carbon Nano-allotrop…
Electrocardiographic Imaging for Atrial Fibrillation: A Perspective From Computer Models and Animal Experiments to Clinical Value
2021
[EN] Electrocardiographic imaging (ECGI) is a technique to reconstruct non-invasively the electrical activity on the heart surface from body-surface potential recordings and geometric information of the torso and the heart. ECGI has shown scientific and clinical value when used to characterize and treat both atrial and ventricular arrhythmias. Regarding atrial fibrillation (AF), the characterization of the electrical propagation and the underlying substrate favoring AF is inherently more challenging than for ventricular arrhythmias, due to the progressive and heterogeneous nature of the disease and its manifestation, the small volume and wall thickness of the atria, and the relatively large…
Cirugía de liberación del túnel carpiano: variabilidad e impacto de la cirugía ambulatoria en la Comunidad Valenciana
2013
Objective: This study aimed to analyze variability in rates of carpal tunnel release surgery among the healthcare areas of the autonomous region of Valencia, and to evaluate the contribution of ambulatory surgery and referrals to private hospitals to the variability found. Methods: We carried out a cross-sectional, population-based study, describing the rates of carpal tunnel release surgery, standardized by age and sex, among areas in the region of Valencia in 2006. The observed variation was then analyzed using small-area analysis methods. Data from hospital admissions, referrals to private hospitals, population statistics and hospital resources were used to construct standardized rates, …
Haem oxygenase-1 induction reverses the actions of interleukin-1β on hypoxia-inducible transcription factors and human chondrocyte metabolism in hypo…
2013
HO-1 (haem oxygenase-1) catalyses the degradation of haem and possesses anti-inflammatory and cytoprotective properties. The role of inflammatory mediators in the pathogenesis of OA (osteoarthritis) is becoming increasingly appreciated. In the present study, we investigated the effects of HO-1 induction in OA and healthy HACs (human articular chondrocytes) in response to inflammatory cytokine IL-1 β (interleukin-1β) under hypoxic conditions. Hypoxia was investigated as it is a more physiological condition of the avascular cartilage. Hypoxic signalling is mediated by HIFs (hypoxia-inducible factors), of which there are two main isoforms, HIF-1α and HIF-2α. Normal and OA chondrocytes were sti…
Kinetic and thermodynamic insights into interaction of erlotinib with epidermal growth factor receptor: Surface plasmon resonance and molecular docki…
2020
Abstract Epidermal growth factor receptor (EGFR) plays an important role in cell proliferation at non-small cell lung cancer (NSCLC). Therefore, targeted therapy of cancer via this kind of receptor is highly interested. Small molecule drugs such as erlotinib and gefitinib inhibit EGFR tyrosine kinase and thus suppress cell proliferation. At this paper, erlotinib interaction with EGFR on the cell surface was studied via surface plasmon resonance (SPR) and molecular docking methods. Kinetic parameters indicated that erlotinib affinity toward EGFR was increased through increment of temperature. The thermodynamic analysis showed that van der Waals and hydrogen binding forces play a major role i…
Transcriptome-wide identification of transient RNA G-quadruplexes in human cells
2018
Guanine-rich RNA sequences can fold into four-stranded structures, termed G-quadruplexes (G4-RNAs), whose biological roles are poorly understood, and in vivo existence is debated. To profile biologically relevant G4-RNA in the human transcriptome, we report here on G4RP-seq, which combines G4-RNA-specific precipitation (G4RP) with sequencing. This protocol comprises a chemical crosslinking step, followed by affinity capture with the G4-specific small-molecule ligand/probe BioTASQ, and target identification by sequencing, allowing for capturing global snapshots of transiently folded G4-RNAs. We detect widespread G4-RNA targets within the transcriptome, indicative of transient G4 formation in…