• The known crystal structures of class C GPCR VFTs do

  2024-09-28

  

  The known crystal structures of class C GPCR VFTs do not include attached TM domains, therefore current conformational data may not accurately reflect the dynamics of extracellular domains in full-length receptors. Nevertheless, compelling mechanisms of signal transduction can still be postulated. S

• Despite these conflicting data about COX ER

  2024-09-28

  

  Despite these conflicting data about COX-2/ER correlations, a large body of evidence supports that elevated COX-2 expression in breast cancer is a constant feature of high stage disease and a predictor of worse outcome. Upregulation of COX-2 protein has been identified in approximately 40% of cases

• As with most G protein coupled receptors GPCRs sustained act

  2024-09-28

  

  As with most G protein-coupled receptors (GPCRs), sustained activation of APJ can cause desensitization and this has been reported to occur for APJ-mediated effects on cytoplasmic Ca2+ concentration, as well as for effects on activity of adenylyl cyclase, ERK and Akt (Ishida et al., 2004, Masri et a

• It has been proposed that a PrP pathogenic mechanism

  2024-09-28

  

  It has been proposed that a PrP pathogenic mechanism is a toxic gain of function secondary to the misfolding of mutated PrP. However, such a mechanism might not apply to all mutant PrP species, since some mutations had little effect on the stability and folding kinetics of PrP (Swietnicki et al., 19

• EPSP analogs were retrieved from PubChem database and dockin

  2024-09-28

  

  EPSP analogs were retrieved from PubChem database and docking procedure yielded about eight best binding analogs (Fig. 10). The selected molecules were further assessed for their theoretical Ki values using AUTODOCK software version 4. The predicted binding efficiency of retrieved analogs was estima

• Heat shock protein Hsp is a molecular

  2024-09-28

  

  Heat shock protein 90 (Hsp90) is a molecular chaperone that plays a central role in regulating the maturation, activation and stability of numerous “client proteins” that drive the development and progression of many cancers. Therefore, inhibition of Hsp90 would result in degradation of the client p

• Interestingly hypoxia and an enhanced

  2024-09-28

  

  Interestingly, hypoxia and an enhanced Warburg effect ultimately lead to increased lactate production. The accumulation of lactate results in an acidic tumor microenvironment, which induces local inflammation. Lactate also promotes the polarization of macrophages that express immunosuppressive argin

• Metformin s pluripotent roles are alluded to in terms

  2024-09-27

  

  Metformin's pluripotent roles are alluded to in terms of its antitumorigenic, glucose-lowering, and cardioprotective effects, which are due in part to its upregulation of AMPK activity [39,40]. Metformin's glucose-lowering effect is a result of reduced hepatic gluconeogenesis, whereas improved insul

• br Discussion One binding site MB Fig is located in

  2024-09-27

  

  Discussion One binding site, MB327-1 (Fig. 4) is located in the extracellular domain between the γ and α subunits. MB327 adopts an extended conformation in the MB327-1 site and is oriented parallel to the channel. The second putative binding site, MB327-2 (Fig. 4) is situated deep inside the chan

• Drug resistance development often involves structurally un

  2024-09-27

  

  Drug resistance development often involves structurally un-related drugs and, specifically both conventional and targeted agents. IGROV-1/Pt1 biotin 100 mg are characterized by resistance to cisplatin and reduced sensitivity to inhibitors of EGF-R and MEK, the up-stream activator of ERK1/2, associa

• br Materials and methods br Results br

  2024-09-27

  

  Materials and methods Results Discussion Author contributions JH purified protein, performed vanadate inhibition experiments, crystallized, collected data, determined and refined the ATX-VO5 structure, analysed all the structures, prepared the displayed items and supervised ALHE; WJK con

• In HepG cells compound showed inhibition of

  2024-09-27

  

  In HepG2 cells, annexin v staining showed inhibition of total lipid syntheses with an IC of 8μM. A cell based Alamar Blue cytotoxicity assay was used in parallel to differentiate the effect on the inhibition of lipid synthesis versus potential cytotoxicity. Under identical incubation conditions, c

• Tumor suppressor ARF regulates the activity of p

  2024-09-27

  

  Tumor suppressor ARF regulates the activity of p53 by inhibiting the functions of Mdm2. ARF is induced by hyperproliferative signals emanating from oncogenic Ras, overexpressed c-myc, and from deregulated E2F . ARF prevents p53 degradation and leads to increased p53 function by sequestering Mdm2 to

• Telomerase action at the telomere is highly regulated it

  2024-09-27

  

  Telomerase action at the telomere is highly regulated; it preferentially elongates the shortest telomeres, and recruitment of the enzyme complex to the telomere occurs in mid-S phase of the cell cycle (Bianchi and Shore, 2007, Britt-Compton et al., 2009, Teixeira et al., 2004, Hemann et al., 2001, T

• br Results br Discussion ER and

  2024-09-27

  

  Results Discussion ER and GR play opposite phenotypic roles in the normal endometrium, with ER promoting growth and GR inhibiting growth. Here, we show that in endometrial cancer, GR expression is associated with worse outcomes and higher-grade tumors, and this association is observed only in

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