1,721,102 research outputs found
The retinoblastoma gene family: Its role in cancer onset and progression
No full textIn the recent past, a considerable amount of scientific literature has revealed impressive mechanisms that exist to safeguard development and homeostasis in high eukaryotes, and has identified a complex molecular machinery regulating proliferation, differentiation and cell death in mammalian cells. Alteration in at least two of these regulatory circuits is essential for transforming normal cells into malignant ones. During the second half of this century, research focused on the identification and characterisation of genes directly involved in malignant transformation and emphasised that tumourigenesis in humans is the result of a multi-step process reflecting genetic alterations, progressively pushing normal cells towards highly malignant derivatives. Because several human tumours involve loss of heterozygosity of tumour suppressor genes, it is now well accepted that mutations of these genes play a key role in malignant transformation. Current approaches in molecular research have aimed at developing more efficient therapies based on restoring the lost function of genes directly involved in malignant transformation. Since the retinoblastoma (RB) gene family, pRb/p105, pRb2/p130 and p107, has been shown to suppress neoplastic growth, these tumour suppressor genes offer an attractive therapeutic target for treating disorders involving cell growth. This review examines the functional regions of RB family members and the involvement of these genes in controlling cell cycle, apoptosis, differentiation and angiogenesis, highlighting the findings of in vitro and in vivo studies, and focusing on the role of RB proteins in tumourigenesis and in the design of potential approaches for gene therapy development. © 2000 Ashley Publications Ltd
Application of the PRINS technique to titer recombinant virus and evaluation of the efficiency of viral transduction
No full textTitration is an important and critical step in dosing recombinant virus for gene therapy, We present a relatively fast, convenient, and sensitive method that allows for precise quantification of recombinant retrovirus. The method is based on PCR amplification of a foreign gene by the PRINS (primer in situ DNA synthesis) technique, The PRINS technique is based on the sequence-specific annealing of unlabeled oligonucleotide DNA in situ, This oligonucleotide operates as a primer for in situ chain elongation catalyzed by the Tag I polymerase, Using digoxygenin-labeled nucleotides as a substrate for chain elongation, the neo-synthetic DNA is labeled by an FITC-conjugated anti-digoxygenin antibody. To avoid the possibility of false positives, we amplified the puromycin-resistance gene, which is associated with the transgene in the same viral vector and is not normally present in mammalian cells, The retroviral titer was evaluated by counting fluorescein isothiocyanate-positive cells after PRINS labeling, while knowing the number of plated cells that were transduced with different amounts of viral supernatant, A comparable viral concentration of 1 x 10(7) infectious units/mL was found among the retroviruses. (C) 2001 Academic Press
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Insights into SARS-CoV-2: Small-Molecule Hybrids for COVID-19 Treatment
No full textThe advantages of a treatment modality that combines two or more therapeutic agents with different mechanisms of action encourage the study of hybrid functional compounds for pharmacological applications. Molecular hybridization, resulting from a covalent combination of two or more pharmacophore units, has emerged as a promising approach to overcome several issues and has also been explored for the design of new drugs for COVID-19 treatment. In this review, we presented an overview of small-molecule hybrids from both natural products and synthetic sources reported in the literature to date with potential antiviral anti-SARS-CoV-2 activity
pRb2/p130-E2F4/5-HDAC1-SUV39H1-p300 and pRb2/p130-E2F4/5-HDAC1-SUV39H1-DNMT1 multimolecular complexes mediate the transcription of estrogen receptor-alpha in breast cancer
No full textThe estrogen receptor-alpha (ER) plays a crucial role in normal breast development and is also linked to development and progression of mammary carcinoma. The transcriptional repression of ER-alpha gene in breast cancer is an area of active investigation with potential clinical significance. However, the molecular mechanisms that regulate the ER-alpha gene expression are not fully understood. Here we show a new molecular mechanism of ER-alpha gene inactivation mediated by pRb2/p130 in ER-negative breast cancer cells. We investigated in vivo occupancy of ER-alpha promoter by pRb2/p130-E2F4/5-HDAC1-SUV39 H1-p300 and pRb2/p130-E2F4/5-HDAC1-SUV39H1-DNMT1 complexes, and provided a link between pRb2/p130 and chromatin-modifying enzymes in the regulation of ER-alpha transcription in a physiological setting. These findings suggest that pRb2/p130-multimolecular complexes can be key elements in the regulation of ER-alpha gene expression and may be viewed as promising targets for the development of novel therapeutic strategies in the treatment of breast cancer, especially for those tumors that are ER negative
Modulation of cell cycle components by epigenetic and genetic events
No full textCell cycle progression is monitored by surveillance mechanisms, or cell cycle checkpoints, that ensure that initiation of a later event is coupled with the completion of an early cell cycle event. Deregulated proliferation is a characteristic feature of tumor cells. Moreover, defects in many of the molecules that regulate the cell cycle have been implicated in cancer formation and progression. Key among these are p53, the retinoblastoma protein (pRb) and its related proteins, p107 and pRb2/p130, and cdk inhibitors (p15, p16, p18, p19, p21, p27), all of which act to keep the cell cycle from progressing until all repairs to damaged DNA have been completed. The pRb (pRb/p16 INK4a/cyclin D1) and p53 (p14ARF/mdm2/p53) pathways are the two main cell-cycle control pathways frequently targeted in tumorigenesis, and the alterations occurring in each pathway depend on the tumor type. Virtually all human tumors deregulate either the pRb or p53 pathway, and oftentimes both pathways simultaneously. This review focuses on the genetic and epigenetic alterations affecting the components of mechanisms regulating the progression of the cell cycle and leading to cancer formation and progression. © 2005 Elsevier Inc. All rights reserved
Induzione apoptotica in linee cellulari B, T e mieloidi: il ruolo della molecola CD38.
No full textVi Congresso AIB
- …
