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

Leiomyoma is the most common benign smooth muscle tumor. Although rare in other organs, it is frequent in the uterus, occurring in nearly 40% of women over 50 years of age. These benign tumors rarely undergo malignant transformation. The incidence of leiomyosarcomas in uterine leiomyomas is estimated to be between 0.13 and 0.29%. Little is known of the genetic abnormalities leading to this neoplasia. Loss of p53 function has been implicated in the pathogenesis of many human tumors. We evaluated eight leiomyosarcomas and eight leiomyomas for alterations in exons 5-8 of p53, which are the mutational hotspots for this gene in human malignancies. Genomic DNA of the samples was studied by single-strand conformation polymorphism (SSCP) analysis and positive samples were analyzed by direct sequencing of PCR-amplified products. Each exon was studied individually, and positive controls were used for each exon. Three alterations in a total of eight leiomyosarcoma samples were found; the changes were point mutations (exon 5, codon 165; exon 8, codon 275; exon 8, codon 266). No alterations of p53 could be demonstrated in the eight leiomyoma samples. Our results show for the first time that p53 mutations are frequent in leiomyosarcomas, and one distinguishing difference between benign leiomyomas and some malignant leiomyosarcomas is the acquisition of a p53 mutation.
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PMID:p53 alterations in uterine leiomyosarcomas versus leiomyomas. 806 47

Li-Fraumeni syndrome(LFS) is an autosomal dominant disorder that predisposes individuals to multiple forms of cancer including breast cancer, soft tissue sarcoma, brain tumor, osteosarcoma, leukemia, and adrenocortical carcinoma. Recently, germ-line mutation of the p53 tumor suppressor gene has been implicated in this familial disorder. We report a case of a 25-year old woman who presented with bilateral breast cancer and uterine leiomyoma. Her mother had died of early-onset bilateral breast cancer. And her younger sister had breast carcinoma as well, which was identified at the age of 22, indicating her strong familial history. To test for the presence of the p53 germ-line mutation, we analyzed the genomic DNA from the peripheral blood of the proband and her sister by PCR-SSCP analysis of exon 5 through exon 8 of the p53 gene. As a result, a p53 mutation in exon 7 was detected in an allele, and it was shared with her sister as the same pattern. Sequencing analysis determined the altered nucleotide at codon 248(CGG > TGG) which is one of the most frequent mutation sites related to LFS. Therefore, this patient has the most consistent characteristic features of LFS phenotype and it is believed that this case is the first report of a family with Li-Fraumeni syndrome carrying the p53 germ-line mutation in Korea.
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PMID:The first documentation of Li-Fraumeni syndrome in Korea. 852 48

To discuss the diagnosis of uterine leiomyosarcoma and leiomyoma of cellular and bizarre type, we reviewed 51 cases and carried out P53 and desmin immunohistochemical staining on 43 cases. We found that in most cases leiomyosarcoma is accompanied by nuclear mitosis, cell atypia and margin infiltration. In a small number of cases, though mitotic figures are scarce, high cell atypia and marked margin infiltration were present. Leiomyoma variants may have high cellular density and bizarre nuclears but have no margin infiltration. Leiomyosarcoma has a high incidence of P53 expression, while no P53 expression was detected in leiomyoma variants. Desmin expression is closely correlated with the differentiation of smooth muscle neoplasms of the uterus. We conclude that nuclear mitotic activity is an important but not independent criteria in the diagnosis of uterine leiomyosarcoma. Cellular atypia and margin infiltration should be considered. P53 and desmin expression can be applied as accessary criteria.
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PMID:[Smooth muscle neoplasms of the uterus--a 51 cases study]. 938 67

Uterine leiomyoma is a mesenchymal tumor composed of smooth muscle cells with fibrous tissues and many mast cells. Tranilast is known to suppress fibrosis or to work as a mast cell stabilizer and is reported to inhibit proliferation of vascular smooth muscle cells. In this study, we examined the effects of tranilast on cultured human leiomyoma cells in vitro to evaluate whether this agent has the potential to inhibit the growth of uterine leiomyomas. Tranilast inhibited the proliferation of cultured leiomyoma cells in a dose-dependent manner without any cytotoxic effect or induction of apoptosis. In association with the inhibitory effect, tranilast induced the cyclin-dependent kinase (CDK) inhibitor p21(waf1) and tumor suppressor gene p53 and decreased CDK2 activity. These results suggest that tranilast arrests the proliferation of uterine leiomyoma cells at the G0/G1 phase, through the suppression of CDK2 activity via an induction of p21(waf1) and p53. Tranilast was concluded to be a potent agent to inhibit proliferative activity of uterine leiomyoma cells.
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PMID:Tranilast inhibits the proliferation of uterine leiomyoma cells in vitro through G1 arrest associated with the induction of p21(waf1) and p53. 1246 60

Uterine leiomyosarcoma (ULMS) is an aggressive gynecological disease. Although ULMS are often found in association with benign leiomyoma (LMA), little is known regarding the relationship between these benign and malignant smooth muscle neoplasms. The objective of this study was to evaluate the expression of epidermal growth factor (EGFR), platelet-derived growth factor (PDGFR), and p53 in ULMS specimens, their prognostic relevance, and the expression of these molecular markers when compared to benign LMA specimens. Between 1991 and 2001, 25 patients were identified with high-grade primary ULMS and for whom tissue was available. Tissue microarray was created with three representative cores from each of the ULMS cases as well as from 19 patients with benign uterine leiomyomata. Immunohistochemical (IHC) staining was performed for EGFR, PDGFR, and p53. Negative and positive IHC staining was scored for each marker. Outcome analysis was performed only for ULMS. Survival was determined from the time of initial diagnosis to last follow-up. Twelve (48%) ULMS expressed p53 compared to none of the LMA (P < 0.001), and 15 (60%) ULMS cases showed PDGFR expression compared to 32% of LMA samples (P= 0.08). EGFR expression did not differ between ULMS and LMA groups. ULMS patients with p53 expression had a poorer survival compared to ULMS patients with negative expression (P= 0.07). ULMS tumor stage had the strongest association with overall survival (P= 0.05). Our study supports previous investigations indicating that p53 expression may serve as a prognostic marker for ULMS patients. The difference in PDGFR expression between ULMS and LMA demonstrated a trend toward significance. EGFR was not commonly expressed in ULMS. These uniquely expressed markers may assist in stratifying patients by survival and identify novel therapeutic markers. Clearly, further investigation is needed.
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PMID:p53, epidermal growth factor, and platelet-derived growth factor in uterine leiomyosarcoma and leiomyomas. 1668 72

Isoliquiritigenin(ISL), a calchone flavonoid, has cancer-preventing properties and is often used in Chinese medicine. In the present study, the authors use ISL to determine its effect on cell proliferation and cell cycle progression in primary cultured human uterine leiomyoma cells. Cell viability and cell proliferation assays were conducted. Flow cytometry, annexin V apoptosis assay, and DNA fragmentation assay were performed to determine the effect of ISL on cell cycle and apoptosis. The expression of cell cycle regulatory-related proteins was evaluated by Western blot. The cell viability and proliferation of uterine leiomyoma cells were significantly reduced by ISL treatment in a dose-dependent manner. Flow cytometry results showed that ISL induced subG1 and G2/M arrest. DNA fragmentation assay and annexin V apoptosis assays revealed apoptosis induction. ISL-induced growth inhibition in uterine leiomyoma cells was associated with increased p21(Cip1/) Waf1 expression in a p53-dependent manner. Activation of caspase-3 and downregulation of Bcl-2, cdk 2/4, and E2F, with a concomitant increase in dephosphorylation of Rb and poly-ADP-ribose polymerase cleavage, were observed. This study demonstrates that ISL inhibits cell proliferation by initiating apoptosis in human uterine leiomyoma cells coupled with increased cell cycle arrest. These results indicate that ISL could prove to be a promising chemopreventive and therapeutic agent against human uterine leiomyoma.
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PMID:Induction of growth inhibition and apoptosis in human uterine leiomyoma cells by isoliquiritigenin. 1848 28

Observations from the authors' laboratory suggest a physiological role for increased cyclin G1 protein levels in human uterine leiomyoma. The hypothesis of the present study is that the strategic modulation of cyclin G1 by antisense technology will inhibit the survival of in vitro-grown uterine leiomyoma cells. Cultured uterine leiomyoma cells were transfected with cyclin G1 ribbon-type antisense oligonucleotide (cyclin G1 RiAS) to effectively reduce cyclin G1 expression. Cell viability, in situ terminal deoxyuridine nick end-labeling (TUNEL) assay, flow cytometry, DNA fragmentation, and expression of cell cycle regulatory-related proteins were evaluated by Western blot. Antisense oligonucleotides compromised uterine leiomyoma cell viability and inducted apoptosis in a caspase-independent mechanism. In situ TUNEL and DNA fragmentation revealed apoptosis induction, and fluorescent-activated cell sorting analysis showed increased sub-G1-phase cells. Furthermore, abrogation of cyclin G1 enhanced p53 accumulation, phosphorylation of p53 at Ser-15 residue, and increased expression of cyclin-dependent kinase inhibitors p21 and p27. These data imply that cyclin G1 expression is associated with growth promotion and the potential utility and novelty of using ribbon-type antisense oligonucleotides as a gene therapy strategy to treat human uterine leiomyoma.
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PMID:Loss of cyclin g1 expression in human uterine leiomyoma cells induces apoptosis. 1849 47

The authors present the first case of a pure osteosarcoma arising in a long-standing uterine leiomyoma along with a literature review of all heterologous sarcomas arising in uterine leiomyoma. Most cases present with abnormal vaginal bleeding and symptoms related to a rapidly enlarged pelvic mass in postmenopausal women with a long-standing history of uterine leiomyoma. The histological finding of the case in this study revealed a relatively well-circumscribed tumor with a peripheral ring of leiomyoma and a central osteosarcoma. The case in this study further supported a possible pathogenesis involving the p53 gene. The prognosis may be better with low-stage tumor; however, cases with advanced stages, larger tumor size at presentation, and histological type of epithelioid angiosarcoma had poorer prognosis despite aggressive therapy.
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PMID:Osteosarcoma arising in a long-standing uterine leiomyoma: a case report and literature review. 1901 61

It is uncertain whether uterine leiomyosarcoma arises de novo or in preexisting leiomyoma. Leiomyoma-like areas can be seen associated with uterine leiomyosarcoma, raising the possibility of precursor lesions for uterine leiomyosarcoma. In this study, we examined cases of uterine leiomyosarcoma associated with leiomyoma-like areas at the histological, immunohistochemical and DNA level to further evaluate if benign-looking leiomyoma-like and uterine leiomyosarcoma areas are related. Cases of uterine leiomyosarcoma observed at the New York University Medical Center from 1994 to 2007 were reviewed for the presence of leiomyoma-like areas. Of the 26 cases of uterine leiomyosarcoma observed during this period, 18 cases had an associated leiomyoma-like area (five cellular leiomyoma, four symplastic leiomyoma, four cellular and symplastic leiomyoma and five usual type leiomyoma). Sixteen of the 18 cases were examined immunohistochemically for Ki-67, for estrogen receptor, progesterone receptor and for p53. Immunohistochemical profiles were as expected for leiomyoma-like (the mean expression of p53, ER, PR and Ki-67 at 0.3, 63, 75 and 0.6%, respectively), symplastic leiomyoma-like areas (the mean expression of p53, ER, PR and Ki-67 at 0.6, 85, 89 and 5.5%, respectively) and uterine leiomyosarcoma areas (the mean expression of p53, ER, PR and Ki-67 at 52, 38, 39 and 61%, respectively). In six cases, the leiomyoma-like and uterine leiomyosarcoma areas from each case were examined using high-density oligonucleotide array-CGH to determine genetic aberrations in the two areas. Nearly all the genetic aberrations found in leiomyoma-like areas were also found in the corresponding uterine leiomyosarcoma areas. In addition, uterine leiomyosarcoma areas had additional genetic aberrations. The immunohistochemical profiles and genetic aberrations of the examined cases suggest that uterine leiomyosarcoma could arise from the preexisting leiomyoma-like areas that often have a symplastic or cellular morphology.
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PMID:Molecular and immunohistochemical evidence for the origin of uterine leiomyosarcomas from associated leiomyoma and symplastic leiomyoma-like areas. 1963 49

Leiomyosarcomas are malignant smooth muscle tumors that occur most commonly in the gynecologic tract and soft tissue. There are different diagnostic criteria of malignancy for smooth muscle tumors arising at gynecologic and soft tissue sites and they may be managed differently but determining the primary site of a smooth muscle tumor can be difficult in some cases. In addition, the distinction between malignant and benign gynecologic tract smooth muscle tumors on morphologic grounds can be challenging. Using a series of tissue microarrays that contain 245 cases of leiomyosarcomas (102 gynecologic) with survival data, and 49 cases of uterine leiomyoma, we examined the ability of selected immune-markers (estrogen receptor (ER) and WT1) to distinguish between leiomyosarcomas of gynecologic and nongynecologic origin. In addition, we examined whether immunostains for p16, p53 and Ki-67 could distinguish between malignant and benign gynecologic smooth muscle tumors. ER nuclear positivity was observed in 3 and 50% of the nongynecologic and gynecologic leiomyosarcomas, respectively (P<0.001). Nuclear WT1 positivity was seen in 0 and 8% of the nongynecologic and gynecologic leiomyosarcomas, respectively (P<0.001). 87% of primary gynecologic leiomyosarcomas and 2% of uterine leiomyomas showed diffuse (>or=50% of cells) p16 staining (P<0.001). 23% of gynecologic leiomyosarcomas showed p53 immunopositivity (>or=50% of cells) whereas none of the leiomyomas were positive for p53 (P<0.001). 65% of the gynecologic leiomyosarcomas and 0% of the leiomyomas exhibited >10% Ki-67 proliferation index (P<0.001). Diffuse p16 and p53 immunopositivity and high Ki-67 proliferation index, singly or in combination, yielded an overall sensitivity of 92% and specificity of 98% for distinguishing between gynecologic leiomyosarcomas and leiomyomas and can be used as indicators of malignancy for gynecologic smooth muscle tumors. Although ER positivity can be used to support the gynecologic origin of a leiomyosarcomas, nuclear WT1 immunostaining is of little use.
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PMID:A panel of antibodies to determine site of origin and malignancy in smooth muscle tumors. 1973 47


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