45,893 research outputs found
GSK-3 beta inhibition - At the crossroad between Akt and mTOR constitutive activation to enhance cyclin D1 protein stability in mantle cell lymphoma
No full textStrategies able to downregulate the aberrant expression of cyclin D1 may prove of therapeutic relevance in cancer patients. This is particularly true for mantle cell lymphoma (MCL) in which cyclin D1 is overexpressed as a consequence of the t(11;14)(q13;q32) translocation. We have recently demonstrated that an increased cyclin D1 stability also contributes to the high levels of this protein observed in MCL cells. This effect is mediated by a constitutive activation of PI3-K/Akt, which keeps GSK-3β inhibited. Here we show that inhibition of PI3-K/Akt induces a 40% decrease of cyclin D1 half-life as a result of accumulation of the dephosphorylated/active form of GSK-3β within the nucleus, where this kinase can phosphorylate cyclin D1 on Thr286 thereby promoting its nuclear export. Translocation of cyclin D1 into the cytoplasm is mediated by the nuclear exportin CRM1, whose association with cyclin D1 increases following PI3-K/Akt inhibition. Notably, rapamycin downregulated GSK-3β Ser9 phosphorylation with concurrent nuclear export of cyclin D1 only in MCL cells in which GSK-3β is under the control of mTOR. These findings suggest that the ability to downregulate cyclin D1 through GSK-3β may identify subsets of MCL patients who may benefit from the treatment with mTOR inhibitors and stimulate further studies to assess whether the inability to affect GSK-3β activity may constitute a clinically relevant resistance factor to mTOR inhibitors. ©2008 Landes Bioscience
CMTM4 as a new partner for IL‐17 receptor: Adding a piece in the puzzle of IL17‐driven diseases
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Statement: Col. Samuel Simmons on Fremont, December 2, 1896
No full textStatement of Col. Samuel Simmons, of St. Louis, to J. McCan Davis, December 2, 1898. Simmons speaks of paying the enlisted men
Statement: Col. Samuel Simmons on Fremont, December 2, 1896
No full textStatement of Col. Samuel Simmons, of St. Louis, to J. McCan Davis, December 2, 1898. Simmons speaks of paying the enlisted men
Mock, Col. Alfred J., July 20, 1993 [Interview]
No full textCol. Alfred J. Mock was interviewed on July 20, 1993, by Michael Birkner and David Hedrick about his relationship with Gettysburg graduate Stephen H. Warner, a Public Information Officer killed in the Vietnam War.Pyle, Ernie; Safer, Morley; Rather, Dan; Arnett, Peter; Warner, Stephen H.; Abrams, Gen. Creighton; Westmoreland, Gen. William C.; Goralski, Robert
Epstein-Barr virus and telomerase: from cell immortalization to therapy
No full textOvercoming cellular senescence is strictly required for virus-driven tumors, including those associated with Epstein-Barr virus (EBV). This critical step is successfully accomplished by EBV through TERT expression and telomerase activation in infected cells. We herein review the complex interplay between EBV and TERT/telomerase in EBV-driven tumorigenesis. Evidence accumulated so far clearly indicates that elucidation of this issue may offer promising opportunities for the design of innovative treatment modalities for EBV-associated malignancies. Indeed, several therapeutic strategies for telomerase inhibition have been developed and are being investigated in clinical trials. In this respect, our recent finding that TERT inhibition sensitizes EBV+ lymphoma cells to antivirals through activation of EBV lytic replication is particularly promising and provides a rationale for the activation of clinical studies aimed at assessing the effects of combination therapies with TERT inhibitors and antivirals for the treatment of EBV-associated malignancies
Damage-associated molecular patterns modulation by microrna: Relevance on immunogenic cell death and cancer treatment outcome
No full textImmunogenic cell death (ICD) in cancer is a functionally unique regulated form of stress-mediated cell death that activates both the innate and adaptive immune response against tumor cells. ICD makes dying cancer cells immunogenic by improving both antigenicity and adjuvanticity. The latter relies on the spatiotemporally coordinated release or exposure of danger signals (DAMPs) that drive robust antigen-presenting cell activation. The expression of DAMPs is often constitutive in tumor cells, but it is the initiating stressor, called ICD-inducer, which finally triggers the intracellular response that determines the kinetics and intensity of their release. However, the contribution of cell-autonomous features, such as the epigenetic background, to the development of ICD has not been addressed in sufficient depth. In this context, it has been revealed that several microRNAs (miRNAs), besides acting as tumor promoters or suppressors, can control the ICD-associated exposure of some DAMPs and their basal expression in cancer. Here, we provide a general overview of the dysregulation of cancer-associated miRNAs whose targets are DAMPs, through which new molecular mediators that underlie the immunogenicity of ICD were identified. The current status of miRNA-targeted therapeutics combined with ICD inducers is discussed. A solid comprehension of these processes will provide a framework to evaluate miRNA targets for cancer immunotherapy
J. C. L. Sismondi: cos'è l'economia o che cosa avrebbe potuto essere
No full textPrefazione al volume che raccoglie alcuni saggi editi e inediti di Sismondi tradotti e commentati
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