1,721,000 research outputs found
p53 and merlin tumor suppressors: Two of a kind
No full textIn EBioMedicine, Chen and colleagues [1] showed that more than 85% of sporadic vestibular schwannomas have at least one somatic mutation affecting the NF2 gene and that the “two-hits” NF2 gene status is associated with larger tumor size and with loss of merlin protein expression. This situation is associated with a significant decrease of p53 protein level and functions, due to enhanced nuclear accumulation of MDM2 and consequent nuclear export of p53 for degradation. The authors correlate this discovery with the relevant role of MDM2 as mediator of merlin and p53 interaction: in the normal Schwann cells they are both regularly present and reciprocally stabilized, while in Schwannoma p53 is rapidly degraded because of a higher presence of MDM2 in the absence of merlin expression. Importantly, the authors demonstrated that the combined inhibition of MDM2 and proteasome by the two drugs Nutlin-3 and MG-132 was able to restoring p53 and merlin normal level and normal biological activity (apoptosis induction and cell cycle blockade) and to efficiently reduce the growth of schwannoma in vivo. Their findings offer new opportunities both for preclinical and clinical research
Osservazioni sulle variazioni di proteina, olio e altri componenti durante la maturazione di alcune varietà di colza (Brassica napus L. oleifera D.C.).
No full textVariazioni del contenuto in olio ed in proteina del seme intero di soia (Soja hispida Moench.) in relazione all'epoca di semina.
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Soybean nodules development and nitrogenase activity during the reproductive phase: statistical modeling approach.
No full textActivation of PKC-e counteracts maturation and apoptosis of HL-60 myeloid leukemic cells in response to TNF family members.
No full textProtein kinase C (PKC)-epsilon, a component of the serine/threonine PKC family, has been shown to influence the survival and differentiation pathways of normal hematopoietic cells. Here, we have modulated the activity of PKC-epsilon with specific small molecule activator or inhibitor peptides. PKC-epsilon inhibitor and activator peptides showed modest effects on HL-60 maturation when added alone, but PKC-epsilon activator peptide significantly counteracted the pro-maturative activity of tumor necrosis factor (TNF)-alpha towards the monocytic/macrophagic lineage, as evaluated in terms of CD14 surface expression and morphological analyses. Moreover, while PKC-epsilon inhibitor peptide showed a reproducible increase of TNF-related apoptosis inducing ligand (TRAIL)-induced apoptosis, PKC-epsilon activator peptide potently counteracted the pro-apoptotic activity of TRAIL. Taken together, the anti-maturative and anti-apoptotic activities of PKC-epsilon envision a potentially important proleukemic role of this PKC family member
Profiles of non-structural carbohydrates in two soybean varieties with different growth habits.
No full textActively targeted nanocarriers for drug delivery to cancer cells
No full textIntroduction: Progressive breakthroughs in nanomedicine have been instrumental for the clinical translation of actively targeted drug-delivery approaches. Besides storing large payloads of drugs within the nanoparticle core, the conjugation of targeting moieties confers specific targeting ability to the nanoplatforms. In this respect, clinical results suggest that actively targeted nanocarriers can exhibit an overall improved antitumor efficacy, minimizing off-target toxicity. Areas covered: This review article summarizes the advances in active targeting of nanocarriers to cancer cells. Specifically, we discuss the various types of nanocarriers, describe the receptors that are frequently overexpressed in solid tumors, and discuss how this approach can be used to improve clinical outcomes. We particularly focus on ongoing clinical trials of actively targeted nanoparticles that are yet to be clinically approved. Expert opinion: Further investment in active targeting will likely pose clinical benefits. We envisage a future requiring the use of longitudinal measures in the clinical setting to profile the patients that are likely to benefit from actively targeted nanocarriers. At the preclinical stage, a complete picture of intratumoral barriers combined with a quantitative approach of the intratumoral fate of nanomaterials will be instrumental in defining more effective strategies to improve their clinical translation
Perifosine selectively induces cell cycle block and modulates retinoblastoma and E2F1 protein levels in p53 mutated leukemic cell lines.
No full textThe effect of the single-chain alkylphospholipid perifosine was analyzed in p53(wild-type) (SKW6.4, OCI and MOLM), p53(mutated) (BJAB, MAVER) and p53(null) (HL-60) leukemic cell lines. Perifosine promoted cytotoxicity with a combination of apoptosis induction in all cell lines and cell cycle block at the G(2)M checkpoint, which was selectively observed in p53(mutated) BJAB and MAVER cell lines. At the molecular level, perifosine induced hypophosphorylation of retinoblastoma protein and the degradation of E2F1 protein in p53(mutated) but not in p53(wild-type) cells. These data indicate that perifosine potentially represents an innovative therapeutic approach for p53(mutated) hematological malignancies
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