Disease relevance of Critical Pathways

• BACKGROUND: Hypoxia-inducible factor-1 (HIF-1) is a transcription factor that regulates gene expression in critical pathways involved in tumor growth and metastases [1].
• Together these studies reveal the presence of c-Rel-dependent pathways critical for IL-12p40 production in response to inflammatory stimuli and demonstrate a novel c-Rel-independent pathway of IL-12p40 production during toxoplasmosis [2].
• Hypoxia stimulates a number of pathways critical to cancer cell survival, including the activation of vascular endothelial growth factor (VEGF) transcription [3].
• On the basis of the EGFR and MDM2 role in integrating signaling pathways critical for prostate cancer progression, we investigated whether their selective combined blockade may have a cooperative antitumor effect in prostate cancer [4].
• The results suggest a central role for TNF-alpha in the mechanistic pathways critical to lung inflammation [5].

Psychiatry related information on Critical Pathways

• Further exploration of this database will provide additional insights into genes and pathways critical for olfactory neurogenesis, neuronal differentiation, olfaction, and mucosal defense [6].
• The S-1 clinical pathway includes a pathway for clinicians, a pathway for patients, and such assist tools as a medication diary, an explanatory document containing instructions relating to patient compliance, a table of associations between adverse reactions and prodromes, and general principles for dose reduction and withdrawal [7].

High impact information on Critical Pathways

• The MAML (mastermind-like) proteins are a family of three co-transcriptional regulators that are essential for Notch signaling, a pathway critical for cell fate determination [8].
• Thus, regulation of the JNK pathway provides an interesting example of how many different stimuli can converge into regulating pathways critical for the determination of cell fate [9].
• A summary is provided of recent studies examining the electrophysiological properties of CCK cells and newly discovered proteins that act as releasing factors for CCK, which mediate feedback pathways critical for regulated secretion in the intact organism [10].
• This interaction may impart functional specificity to GATA factors and provide cooperative crosstalk between two pathways critical for early cardiogenesis [11].
• Raf induces NF-kappaB by membrane shuttle kinase MEKK1, a signaling pathway critical for transformation [12].

Chemical compound and disease context of Critical Pathways

• Our recent studies have demonstrated that Smad signalling is also a critical pathway for renal fibrosis induced by other pro-fibrotic factors, such as angiotensin II and advanced glycation end products (AGE) [13].

Biological context of Critical Pathways

• Analysis of the regulated genes supports the concept that GC-induced apoptosis results from positive GR autoregulation entailing persistent down-regulation of metabolic pathways critical for survival[14]
• Investigations have also indicated that p21 may regulate nucleotide excision repair, a critical pathway that removes carcinogenic DNA damage induced by UV light and other mutagens [15].
• CD45, a leukocyte-specific transmembrane protein tyrosine phosphatase, mediates signal transduction pathways critical for immune responses [16].
• We also provide evidence for cross-talk among the Rac, Raf, and phosphatidylinositol 3-kinase pathways critical for regulation of MMP-2 and MMP-9 expression and invasive phenotype [17].
• Our findings suggest that methylation of the genes in the critical pathways is common in NPC [18].

Anatomical context of Critical Pathways

• Although a number of candidate molecules have been identified that are capable of delivering a costimulatory signal, increasing evidence suggests that one such critical pathway involves the interaction of the T-cell surface antigen CD28 with its ligand B7, expressed on APCs [19].
• Hepatocyte nuclear factor 4 (HNF-4) is a liver enriched transcription factor that regulates a large number of liver-specific genes, which play important roles in the critical pathways modulated by the response to injury [20].
• Altogether, these data suggest that a critical pathway for T cell development in the human thymus likely involves the permanent activation of Vav in vivo [21].
• The human epidermal growth factor receptor (HER) family of receptor tyrosine kinases controls critical pathways involved in the differentiation, growth, division, and motility of normal epithelial cells [22].
• Results from these experiments demonstrate that lipopolysaccharides (LPS) activate Toll/IL-1 signaling and IL-1 receptor-associated kinase-1 (IRAK1), a critical pathway intermediate in the heart, indicating that the function of this pathway is not limited to immune system tissues [23].

Associations of Critical Pathways with chemical compounds

• S-Adenosylmethionine-dependent transmethylation reactions are required for many critical pathways in human cells [24].
• Thus, PKC activation in this system is essential, one critical pathway regulated by PKC activity is the production of O2-, and continued PKC activity is required for optimal oxidation of LDL lipids [25].
• RESEARCH DESIGN AND METHODS: A pre-post quasi-experimental study design was used to evaluate the implementation of two quality improvement interventions: 1) revision of the hospital's capillary blood glucose monitoring form into a color-coded process control chart and 2) a clinical path for type 2 diabetes as a secondary diagnosis [26].
• A metabolic pathway critical for detoxification of 2,3-epoxy-4-hydroxynonanal involves the ring-opening by epoxide hydrolase, which abolishes its ability to form cyclic etheno DNA adducts [27].
• The data obtained indicate that heme oxygenase, known to be a stress-inducible gene, may be involved in cellular pathways critical to the carcinogenic activity of Cr(VI) in normal human lung cells [28].

Gene context of Critical Pathways

• These findings imply that the scrambler gene product may function in a molecular pathway critical for neuronal migration that is tightly linked to, but downstream of, reelin [29].
• Thus, both c-Cbl and Cbl-b can initiate a phosphatidylinositol 3-kinase/protein kinase B-independent signaling pathway critical to insulin-stimulated GLUT4 translocation [30].
• In this review, we summarize our current understanding of ICAM-1 gene regulation with a particular emphasis on the transcription factors and signal transduction pathways critical for the cell type- and stimulus-specific activation of ICAM-1 gene transcription [31].
• JNK may therefore represent a critical pathway for cytokine production in HASMC [32].
• Wnt/beta-catenin/tcf signaling: a critical pathway in gastrointestinal tumorigenesis [33].

Analytical, diagnostic and therapeutic context of Critical Pathways

• Regarding "Impact of a critical pathway on postoperative length of stay and outcomes after infrainguinal bypass" [34].
• METHODS: In 1995, we initiated a critical pathway for RRP that included epidural anesthesia with or without spinal anesthesia and postoperative methadone, acetaminophen, and ibuprofen for pain control [35].
• Development of clinical pathway in S-1 chemotherapy for gastric cancer [7].
• The intervention was a clinical pathway involving rapid rehydration using N/2 saline + 2.5% dextrose intravenously at 20 mL/kg per h for 2 h, or Gastrolyte R (Aventis Pharma, Lane Cove, NSW, Australia) via nasogastric tube at the same rate [36].
• It can be speculated that the work by Lewis Sheiner reflected in the FDA document titled "Innovation or Stagnation: Challenge and Opportunity on the Critical Path to New Medical Products" made this scientific approach to the drug approval process possible [37].

References