Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glioblastoma multiforme (GBM) is a high grade glial tumor, primarily located in cerebral hemispheres. The most common clinical presentations are slowly progressive neurological deficit such as motor weakness, seizure, and headaches that last less than three months. Calvarium and extra-axial invasion are very rare and generally occur after a brain biopsy or surgery, or secondary to radiotherapy of primary intra-axial glial tumors. We report a case of GBM with calvarium involvement in a 60-year-old man who presented with a frontal bump and left-sided clumsiness. Imaging studies revealed a tumoral lesion that destroyed the frontal bone with white matter involvement of the frontal lobe and extension into the corpus callosum. Histopathological examination of intra-axial and extra-axial lesions revealed pleomorphic high-grade tumor with large areas of necrosis and hemorrhage. Immunohistochemical (IHC) studies confirmed GBM that spread directly into the dura, galea, and calvarium (positive reaction for GFAP, S-100, CD68, OLIG2, and p53). The patient was treated with radiotherapy (60Gy/30 fractions) and concomitant temozolomide. Unfortunately, the patient died seven months after the initial diagnosis.
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PMID:Calvarium mass as the first presentation of glioblastoma multiforme: A very rare manifestation of high-grade glioma. 2924 75

Alcoholic myopathies are characterized by neuromusculoskeletal symptoms such as compromised movement and weakness. Although these symptoms have been attributed to neurological damage, EtOH may also target skeletal muscle. EtOH exposure during zebrafish primary muscle development or adulthood results in smaller muscle fibers. However, the effects of EtOH exposure on skeletal muscle during the growth period that follows primary muscle development are not well understood. We determined the effects of EtOH exposure on muscle during this phase of development. Strikingly, muscle fibers at this stage are acutely sensitive to EtOH treatment: EtOH induces muscle degeneration. The severity of EtOH-induced muscle damage varies but muscle becomes more refractory to EtOH as muscle develops. NF-kB induction in muscle indicates that EtOH triggers a pro-inflammatory response. EtOH-induced muscle damage is p53-independent. Uptake of Evans blue dye shows that EtOH treatment causes sarcolemmal instability before muscle fiber detachment. Dystrophin-null sapje mutant zebrafish also exhibit sarcolemmal instability. We tested whether Trichostatin A (TSA), which reduces muscle degeneration in sapje mutants, would affect EtOH-treated zebrafish. We found that TSA and EtOH are a lethal combination. EtOH does, however, exacerbate muscle degeneration in sapje mutants. EtOH also disrupts adhesion of muscle fibers to their extracellular matrix at the myotendinous junction: some detached muscle fibers retain beta-Dystroglycan indicating failure of muscle end attachments. Overexpression of Paxillin, which reduces muscle degeneration in zebrafish deficient for beta-Dystroglycan, is not sufficient to rescue degeneration. Taken together, our results suggest that EtOH exposure has pleiotropic deleterious effects on skeletal muscle.
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PMID:Ethanol Exposure Causes Muscle Degeneration in Zebrafish. 2961 56

Rhaponticum carthamoides (Willd.) Iljin. is an endemic plant species, which is important in Siberian medicine. It possesses adaptogenic properties and has been used for treatment of overstrain and weakness after illness, physical weakness, and mental weariness. The roots of this species obtained after Agrobacterium rhizogenes transformation are rich in caffeoylquinic acid derivatives known as strong antioxidant compounds. The study makes the first evaluation of the cytotoxic and genotoxic activity of transformed root extract (Rc TR extract) in various human cancer cell lines: leukemia cells (K-562 and CCRF-CEM) and lung adenocarcinoma cells (A549). It was found that Rc TR extract inhibited the cell viability of all tested cell lines in a concentration-dependent manner, and leukemia cell lines were more sensitive to plant extract than A549 lung cancer cell line. Additionally, the Rc TR extract reduced the mitochondrial membrane potential and demonstrated genotoxicity against tested cell lines by increasing mitochondrial DNA lesions in ND1 and ND5 genes and causing nuclear DNA damage in TP53 gene. Our results show that Rc TR extract may effectively treat cancer cells by inducing dysfunction of mitochondria. Additionally, the role of mtDNA may be a promising factor in chemotherapy, and it needs further studies.
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PMID:Rhaponticum carthamoides Transformed Root Extract Has Potent Anticancer Activity in Human Leukemia and Lung Adenocarcinoma Cell Lines. 3062 75

Age-related skeletal muscle atrophy is a very common and serious condition that remains poorly understood at the molecular level. Several lines of evidence have suggested that the tumor suppressor p53 may play a central, causative role in skeletal muscle aging, whereas other, apparently contradictory lines of evidence have suggested that p53 may be critical for normal skeletal muscle function. To help address these issues, we performed an aging study in male muscle-specific p53-knockout mice (p53 mKO mice), which have a lifelong absence of p53 expression in skeletal muscle fibers. We found that the absence of p53 expression in skeletal muscle fibers had no apparent deleterious or beneficial effects on skeletal muscle mass or function under basal conditions up to 6 mo of age, when mice are fully grown and exhibit peak muscle mass and function. Furthermore, at 22 and 25 mo of age, when age-related muscle weakness and atrophy are clearly evident in mice, p53 mKO mice demonstrated no improvement or worsening of skeletal muscle mass or function relative to littermate control mice. At advanced ages, p53 mKO mice began to die prematurely and had an increased incidence of osteosarcoma, precluding analyses of muscle mass and function in very old p53 mKO mice. In light of these results, we conclude that p53 expression in skeletal muscle fibers has minimal if any direct, cell autonomous effect on basal or age-related changes in skeletal muscle mass and function up to at least 22 mo of age.NEW & NOTEWORTHY Previous studies implicated the transcriptional regulator p53 as a potential mediator of age-related skeletal muscle weakness and atrophy. We tested this hypothesis by investigating the effect of aging in muscle-specific p53-knockout mice. Our results strongly suggest that p53 activity within skeletal muscle fibers is not required for age-related skeletal muscle atrophy or weakness.
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PMID:An investigation of p53 in skeletal muscle aging. 3146 16

Introduction: Transformation is a multi-step event wherein indolent lymphomas, such as follicular lymphomas, are converted into an aggressive subtype, such as diffuse large B-cell lymphoma. This process progresses not only through mutations in several of the causative genes, such as TP53, CDKN2A/B, or MYC, but also through epigenetic or micro-environmental changes. Excisional biopsy is recommended when transformation is clinically suspected.Areas covered: The authors summarized the current knowledge regarding the clinicopathological and molecular features of transformed lymphomas and discussed the relevance of re-biopsy in the diagnosis of transformation, comparing it with noninvasive diagnostic tools [fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) and circulating tumor DNA (ctDNA) analysis].Expert opinion: Pathological confirmation by biopsy is considered the golden standard for diagnosis and is indispensable for determining subsequent treatment strategies. The potential weakness of this approach is its invasiveness and the unavailability of pathological findings outside the biopsied areas. In the context of relapse, PET/CT is used mainly for the selection of the best suitable biopsy site, while ctDNA has the potential for detecting systemic genomic changes associated with relapse before clinical presentation. Future investigations should be focused on combining biopsies with new technologies for an early and accurate diagnosis of transformation.
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PMID:Histological transformation in malignant lymphoma: a possible role of PET/CT and circulating tumor DNA as noninvasive diagnostic tools. 3170 88

Oculopharyngodistal myopathy (OPDM) is an adult-onset inherited neuromuscular disorder characterized by progressive ptosis, external ophthalmoplegia, and weakness of the masseter, facial, pharyngeal, and distal limb muscles. The myopathological features are presence of rimmed vacuoles (RVs) in the muscle fibers and myopathic changes of differing severity. Inheritance is variable, with either putative autosomal-dominant or autosomal-recessive pattern. Here, using a comprehensive strategy combining whole-genome sequencing (WGS), long-read whole-genome sequencing (LRS), linkage analysis, repeat-primed polymerase chain reaction (RP-PCR), and fluorescence amplicon length analysis polymerase chain reaction (AL-PCR), we identified an abnormal GGC repeat expansion in the 5' UTR of GIPC1 in one out of four families and three sporadic case subjects from a Chinese OPDM cohort. Expanded GGC repeats were further confirmed as the cause of OPDM in an additional 2 out of 4 families and 6 out of 13 sporadic Chinese individuals with OPDM, as well as 7 out of 194 unrelated Japanese individuals with OPDM. Methylation, qRT-PCR, and western blot analysis indicated that GIPC1 mRNA levels were increased while protein levels were unaltered in OPDM-affected individuals. RNA sequencing indicated p53 signaling, vascular smooth muscle contraction, ubiquitin-mediated proteolysis, and ribosome pathways were involved in the pathogenic mechanisms of OPDM-affected individuals with GGC repeat expansion in GIPC1. This study provides further evidence that OPDM is associated with GGC repeat expansions in distinct genes and highly suggests that expanded GGC repeat units are essential in the pathogenesis of OPDM, regardless of the genes in which the expanded repeats are located.
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PMID:Expansion of GGC Repeat in GIPC1 Is Associated with Oculopharyngodistal Myopathy. 3241 82


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