Search results for "Regulatory"
showing 10 items of 740 documents
Impact of microRNAs in Resistance to Chemotherapy and Novel Targeted Agents in Non-Small Cell Lung Cancer
2014
Despite recent advances in understanding the cancer signaling pathways and in developing new therapeutic strategies, non-small cell lung cancer (NSCLC) shows grim prognosis and high incidence of recurrence. Insufficient dis- ruption of oncogenic signaling and drug resistance are the most common causes of tumor recurrence. Drug resistance, in- trinsic or acquired, represents a main obstacle in NSCLC therapeutics by limiting the efficacy both of conventional che- motherapeutic compounds and new targeted agents. Therefore, novel and more innovative approaches are required for treatment of this tumor. MicroRNAs (miRNAs) are a family of small non-coding RNAs that regulate gene expression by sequ…
Biowaiver Monographs for Immediate Release Solid Oral Dosage Forms: Aciclovir
2008
Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing (biowaiver) for the approval of immediate release (IR) solid oral dosage forms containing aciclovir are reviewed. Aciclovir therapeutic use and therapeutic index, pharmacokinetic properties, data related to the possibility of excipient interactions and reported BE/bioavailability (BA) studies were also taken into consideration in order to ascertain whether a biowaiver can be recommended. According to the Biopharmaceutics Classification System (BCS) and considering tablet strengths up to 400 mg, aciclovir would be BCS Class III. However, in some countries also 800 mg tablets are available which …
Biowaiver Monographs for Immediate Release Solid Oral Dosage Forms: Metformin Hydrochloride.
2021
Abstract Data are examined regarding possible waiver of in vivo bioequivalence testing (i.e. biowaiver) for approval of metformin hydrochloride (metformin) immediate-release solid oral dosage forms. Data include metformin's Biopharmaceutics Classification System (BCS) properties, including potential excipient interactions. Metformin is a prototypical transporter-mediated drug and is highly soluble, but only 50% of an orally administered dose is absorbed from the gut. Therefore, metformin is a BCS Class III substance. A BCS-based approval approach for major changes to marketed products and new generics is admissible if test and reference dosage forms have the identical active pharmaceutical …
Biowaiver Monographs for Immediate Release Solid Oral Dosage Forms: Cephalexin Monohydrate.
2019
Literature data and results of experimental studies relevant to the decision to allow waiver of bioequivalence studies in humans for the approval of immediate release solid oral dosage forms containing cephalexin monohydrate are presented. Solubility studies were performed in accordance with the current biowaiver guidelines of the Food and Drug Administration, World Health Organization and European Medicines Agency, taking the degradation at some pH values into consideration. Together with solubility and permeability data for cephalexin monohydrate from the literature, it was demonstrated to be a Biopharmaceutics Classification System Class 1 drug. The pharmacokinetic behavior, results of b…
Inferring slowly-changing dynamic gene-regulatory networks
2015
Dynamic gene-regulatory networks are complex since the interaction patterns between their components mean that it is impossible to study parts of the network in separation. This holistic character of gene-regulatory networks poses a real challenge to any type of modelling. Graphical models are a class of models that connect the network with a conditional independence relationships between random variables. By interpreting these random variables as gene activities and the conditional independence relationships as functional non-relatedness, graphical models have been used to describe gene-regulatory networks. Whereas the literature has been focused on static networks, most time-course experi…
Hub-Centered Gene Network Reconstruction Using Automatic Relevance Determination
2012
Network inference deals with the reconstruction of biological networks from experimental data. A variety of different reverse engineering techniques are available; they differ in the underlying assumptions and mathematical models used. One common problem for all approaches stems from the complexity of the task, due to the combinatorial explosion of different network topologies for increasing network size. To handle this problem, constraints are frequently used, for example on the node degree, number of edges, or constraints on regulation functions between network components. We propose to exploit topological considerations in the inference of gene regulatory networks. Such systems are often…
Pathway network inference from gene expression data
2014
[EN] Background: The development of high-throughput omics technologies enabled genome-wide measurements of the activity of cellular elements and provides the analytical resources for the progress of the Systems Biology discipline. Analysis and interpretation of gene expression data has evolved from the gene to the pathway and interaction level, i.e. from the detection of differentially expressed genes, to the establishment of gene interaction networks and the identification of enriched functional categories. Still, the understanding of biological systems requires a further level of analysis that addresses the characterization of the interaction between functional modules. Results: We presen…
PED Mediates AKT-Dependent Chemoresistance in Human Breast Cancer Cells
2005
Abstract Killing of tumor cells by cytotoxic therapies, such as chemotherapy or gamma-irradiation, is predominantly mediated by the activation of apoptotic pathways. Refractoriness to anticancer therapy is often due to a failure in the apoptotic pathway. The mechanisms that control the balance between survival and cell death in cancer cells are still largely unknown. Tumor cells have been shown to evade death signals through an increase in the expression of antiapoptotic molecules or loss of proapoptotic factors. We aimed to study the involvement of PED, a molecule with a broad antiapoptotic action, in human breast cancer cell resistance to chemotherapeutic drugs–induced cell death. We show…
Reciprocal regulation of the human sterol regulatory element binding protein (SREBP)-1a promoter by Sp1 and EGR-1 transcription factors.
2007
AbstractSterol regulatory element binding protein (SREBP)-1a is a transcription factor that is highly expressed in actively growing cells, and is involved in the biosynthesis of cholesterol, fatty acids and phospholipids. We have mapped the minimal human SREBP-1a promoter region to 75bp upstream of the translation start site where we discovered a functional role for the 3 GC-boxes containing overlapping sites for the Sp1 and EGR-1 transcription factors. Intact SP1-binding sites are essential for promoter activity, whereas EGR-1 suppresses the transcription of the human SREBP-1a promoter. These results reveal a novel physiologically relevant transcriptional mechanism for the reciprocal regul…
Multiple copies of SUC4 regulatory regions may cause partial de-repression of invertase synthesis in Saccharomyces cerevisiae.
1992
Transformation to generate multiple copies of regulatory DNA sequences has been used to study the interactions between regulatory proteins and their target sequences, since a high copy number of these sequences may titrate trans-acting regulatory proteins. We have analyzed the synthesis of invertase in yeast strains carrying different SUC genes transformed with the multiple-copy plasmid pSH143, a derivative of pJDB207 containing the promoter and upstream regulatory sequences of SUC4. The results obtained seem to be strain dependent. Under repressing conditions a high copy number of SUC4 promoter regions may cause increased expression of the invertase genes resulting in the synthesis of exte…