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)

Liposarcoma is one of the commonest soft-tissue sarcomas, but very rare in the oral cavity. We present two cases of liposarcoma of the oral cavity, together with the related clinical, histopathological and immunohistochemical findings: one affecting the cheek of a 62-year-old man and the other the gingival maxillary tuber of a 41-year-old woman. At histological examination a diagnosis of liposarcoma was made in both cases. In the first case, immunohistochemical analysis revealed intense positivity for p53, MIB-1, MDM2, and focal positivity for S100 protein and CD34, but was negative for alpharsmooth muscle actin, desmin and CD68. The second case it was intensely positive for p53, MIB-1, S-100, and focal positive for MDM2, but negative for alpha smooth muscle actin, CD34, CD68 and desmin. Histological examination and immunohistochemical profiles in the first case were consistent with pleomorphic liposarcoma, whilst that in the second case with dedifferentiated liposarcoma. Both patients were subjected to surgical treatment with wide surgical margins, without adjuvant radio- or chemotherapy. The first case was lost at follow-up one year after surgery, while the second case has not undergone relapse after seven years. We discuss differential diagnosis, examining the histopathological and immunohistochemical features that are potentially useful for distinguishing this tumor from other malignant adipose tissue tumors.
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PMID:Liposarcoma of the oral cavity--case reports of the pleomorphic and the dedifferentiated variants and a review of the literature. 1721 52

The MDM2-antagonist Nutlin 3A can efficiently induce apoptosis in osteosarcoma cell lines with amplified MDM2. However, Nutlin-based therapy could be even more important in more common sarcoma types where this aberration is frequent. The well- and de-differentiated liposarcomas have complex marker chromosomes, consistently including multiple copies of the MDM2 locus. Since amplification seems to be a primary aberration in these tumors, whereas amplification in osteosarcoma generally is a progression marker, the underlying biological mechanisms may be different. We have therefore investigated the molecular response to Nutlin treatment in several liposarcoma cell lines with such markers, as well as a panel of other sarcoma cell lines. We report that Nutlin efficiently stabilized p53 and induced downstream p53 dependent transcription and apoptosis in liposarcoma cells with amplified MDM2 in vitro. Some effect of Nutlin was also observed on cell lines without amplified MDM2 but with wt TP53, but no apoptosis was induced. The MDM4 protein, reported to interfere with the reactivation of p53, was undetectable in cells with amplified MDM2. Thus, Nutlin represents a promising new therapeutic principle for the treatment of an increasing group of sarcomas.
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PMID:Potential for treatment of liposarcomas with the MDM2 antagonist Nutlin-3A. 1735 36

Data concerning the fine structure of the 12q13-15 amplicon which contains MDM2 and CDK4 in well-differentiated and dedifferentiated liposarcomas (WDLPS/DDLPS) are scarce. We investigated a series of 38 WDLPS/DDLPS using fluorescence in situ hybridization analysis with 17 probes encompassing the 12q13-15 region. In addition, using quantitative RT-PCR we studied the expression of MDM2, CDK4, DDIT3 (CHOP/GADD153), DYRK2, HMGA2, TSPAN31 and YEATS4 (GAS41) in 11 cases. We showed that CDK4 (12q14.1) belonged to a distinct amplicon than MDM2 (12q15). There was no continuity in the amplified sequences between MDM2 and CDK4. Moreover, while MDM2 was amplified and overexpressed in all cases, CDK4 was not amplified or overexpressed in 13% of cases. The centromeric border of the CDK4 amplicon was located immediately downstream the 5' end of DDIT3, a gene known for being involved in myxoid liposarcoma translocations. DDIT3 was amplified in 3 cases and overexpressed in 9 cases. The overexpression of DDIT3 was correlated to the CDK4 amplification and not to its own amplification status. This suggested that the CDK4 amplicon, as well as the overexpression of DDIT3, might be generated by the disruption of a fragile region in 5' DDIT3. HMGA2 was always amplified and rearranged indicating that it plays a central role in WDLPS/DDLPS. HMGA2 rearrangement frequently resulted in a loss of the 3' end region that is a binding site for let-7. We also found a frequent amplification and overexpression of YEATS4, an oncogene that inactivates P53, suggesting that YEATS4 might play an important role together with MDM2 in WDLPS/DDLPS oncogenesis.
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PMID:HMGA2 is the partner of MDM2 in well-differentiated and dedifferentiated liposarcomas whereas CDK4 belongs to a distinct inconsistent amplicon. 1821 54

Breadfruit (Artocarpus communis Moraceae) is cultivated in tropical and subtropical regions as a traditional starch crop and also has potential medicinal properties. The aim of this work was to study the in vitro anticancer activity of compounds isolated from the leaves of Artocarpus communis. Three new geranyl chalcone derivatives including isolespeol (1), 5'-geranyl-2',4',4-trihydroxychalcone (2), and 3,4,2',4'-tetrahydroxy-3'-geranyldihydrochalcone (3), together with two known compounds lespeol (4) and xanthoangelol (5), were isolated from the leaves of Artocarpus communis. The structures of 1- 5 were elucidated by spectroscopy and through comparison with data reported in the literature. The effects of geranyl chalcone derivatives (1- 5) on the viability of human cancer cells (including SW 872, HT-29, COLO 205, Hep3B, PLC5, Huh7, and HepG2 cells) were investigated. The results indicate that isolespeol (1) showed the highest inhibitory activity with an IC 50 value of 3.8 muM in SW 872 human liposarcoma cells. Treatment of SW 872 human liposarcoma cells with isolespeol (1) caused the loss of mitochondrial membrane potential (DeltaPsim). Western blotting revealed that isolespeol (1) stimulated increased protein expression of Fas, FasL, and p53. The expression ratios of pro- and antiapoptotic Bcl-2 family members were also changed by isolespeol (1) treatment to subsequently induce the activation of caspase-9 and caspase-3, which was followed by cleavage of poly (ADP-ribose) polymerase (PARP). These results demonstrate that isolespeol (1) induces apoptosis in SW 872 cells through Fas- and mitochondria-mediated pathways.
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PMID:Cytotoxic effects of new geranyl chalcone derivatives isolated from the leaves of Artocarpus communis in SW 872 human liposarcoma cells. 1876 61

Dedifferentiated liposarcoma is a variant of liposarcoma with a more aggressive course. Mutations of the p53 gene have been found in different types of soft tissue sarcoma. It is generally accepted that p53 mutations in human malignant tumors are often related to a poor prognosis. In our case, analysis of p53 gene mutation in tumor samples was performed. p53 gene mutation was observed in dedifferentiated tumor tissue samples but not in well-differentiated tumor tissue samples. It has been reported that p53 gene mutation occurs most commonly in the retroperitoneum and rarely in other anatomic locations. Herein we report a case of dedifferentiated liposarcoma located at intraperitoneum.
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PMID:Intraperitoneal dedifferentiated liposarcoma: a case report. 1885 97

A 56-year-old woman was referred to us with an asymptomatic nodule on the thigh. The nodule was about 11x7 cm in diameter with a well-demarcated, smooth, surface. Magnetic resonance imaging showed the intensity of the nodule to be entirely monotonous or partially heterogeneous. Histological examination revealed a proliferation of adipocytes varying considerably in size and including many mono- or multivacuolated lipoblasts. Immunohistochemically, some of the tumor cells were positive for p53 and MDM2. Histologically, the atypical lipomatous tumor, lipoblastoma, spindle cell lipoma, pleomorphic liposarcoma, and hibernoma comprised the list of possible, differential diagnoses. We considered our case to be a variant of atypical lipomatous tumor, although it did not correspond to any of the 4 atypical lipomatous tumor subgroups. There has been no recurrence to date.
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PMID:An atypical case of atypical lipomatous tumor. 1903 36

The new Ru(II) chloroquine complexes [Ru(eta(6)-arene)(CQ)Cl2] (CQ = chloroquine; arene = p-cymene 1, benzene 2), [Ru(eta(6)-p-cymene)(CQ)(H2O)2][BF4]2 (3), [Ru(eta(6)-p-cymene)(CQ)(en)][PF6]2 (en = ethylenediamine) (4), and [Ru(eta(6)-p-cymene)(eta(6)-CQDP)][BF4]2 (5, CQDP = chloroquine diphosphate) have been synthesized and characterized by use of a combination of NMR and FTIR spectroscopy with DFT calculations. Each complex is formed as a single coordination isomer: In 1-4, chloroquine binds to ruthenium in the eta(1)-N mode through the quinoline nitrogen atom, whereas in 5 an unprecedented eta(6) bonding through the carbocyclic ring is observed. 1, 2, 3, and 5 are active against CQ-resistant (Dd2, K1, and W2) and CQ-sensitive (FcB1, PFB, F32, and 3D7) malaria parasites (Plasmodium falciparum); importantly, the potency of these complexes against resistant parasites is consistently higher than that of the standard drug chloroquine diphosphate. 1 and 5 also inhibit the growth of colon cancer cells, independently of the p53 status and of liposarcoma tumor cell lines with the latter showing increased sensitivity, especially to 1 (IC50 8 microM); this is significant because this type of tumor does not respond to currently employed chemotherapies.
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PMID:Synthesis, characterization, and in vitro antimalarial and antitumor activity of new ruthenium(II) complexes of chloroquine. 1911 67

The spectrum of lipomatous tumors differs in the adult and pediatric populations, with liposarcoma being rare in children. Nearly 10% of individuals with Li-Fraumeni syndrome develop sarcomas in the first 2 decades of life; however, the frequency of sarcoma types and subtypes in this syndrome is unknown. Two atypical lipomatous tumors/well-differentiated liposarcomas (ALT/WDLS) were identified in the pathology files of our institution in young children from "classical" Li-Fraumeni and Li-Fraumeni variant kindreds with a known germline TP53 mutation (Y220C) in one of the families. The patients were 5 and 6 years of age and the ALT/WDLSs were the first expression of the syndrome. The tumors had a high degree of cellular atypia and differed from sporadic ALT/WDLS by strong nuclear immunoreactivity for p53 and absent mdm2 expression. This is the first report of 2 ALT/WDLSs presenting in children before 10 years of age, both in association with Li-Fraumeni syndrome/variant. ALT/WDLS in a young child should raise the possibility of a cancer predisposition syndrome and, in this setting, the p53(+)/mdm2(-) immunophenotype might be characteristic. Recognition of this lesion and its association is important for early diagnosis and subsequent tumor surveillance in the proband and affected family members.
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PMID:p53+/mdm2- atypical lipomatous tumor/well-differentiated liposarcoma in young children: an early expression of Li-Fraumeni syndrome. 2002 12

P53 is the best known tumor suppressor gene. If p53 is mutated, the ability of the cell to sense and repair DNA defects is lost. Failure of this mechanism increases the risk of malignant transformation and tumorigenesis. P53 overexpression is implicated in many carcinomas. P53 alterations appear to be frequent in bone and soft tissue sarcoma and have a strong negative impact on survival in various subtypes of sarcoma like Ewing's sarcoma, synovial sarcoma, and myxoid liposarcoma. There is also evidence in the literature that p53 may be implicated in bone giant cell tumor behavior. The goal of this pilot retrospective study was to detect p53 mutation in giant cell tumor of bone and correlate it with clinical outcome. We analyzed the presence of p53 mutation in 39 patients with giant cell tumor of bone by means of immunohistochemical staining; 8 tumors expressed mutated p53 protein. Seven of them recurred locally (P<.001) and 2 metastasized to the lung (P<.05). In multivariate analysis/subgroup analysis, local recurrence was still strongly correlated, while metastasis had a weaker correlation. Our findings suggest that p53 mutation in giant cell tumor of bone can be useful in predicting tumor behavior, especially in regard to local recurrence. Limitations of this study include the retrospective data collection, the limited number of patients, and the multifactorial nature of the disease; tumor grade, surgical margins, use of adjuvant therapy, and thoroughness of excision may influence the therapeutic outcome. Despite these limitations, this correlation should be further investigated with larger clinical studies. P53 may be used as a marker for the biologic behavior of giant cell tumor of bone.
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PMID:P53 expression as a prognostic marker in giant cell tumor of bone: a pilot study. 2050 47

The author reports a case of CD34-positive malignant myxoid sarcoma in the retroperitoneum with a dilemma of differential diagnosis in multiple biopsy specimens of different locations. A 79-year-old man was diagnosed with right renal pelvic carcinoma and nephrectomy was performed. The carcinoma was urothelial carcinoma (2 cm in diameter) without invasion. The patient was followed up, and a large retroperitoneal tumor was found two years after the operation. Multiple needle biopsies were performed. The patient then showed a hepatic metastasis, and died of cachexia one year after the detection of the retroperitoneal tumor. The needle biopsy specimens showed spindle cell sarcoma in the myxomatous stroma (80%) and in the non-myxomatous stroma (20%). Immunohistochemically, the tumor cells were positive for vimentin, CD34, CD99, bcl-2 and p53 protein. They were negative for cytokeratins, desmin, alpha-smooth muscle actin, S100 protein, melanosome, CEA, neuron specific enolase, CD68, factor VIII-related antigen, CD31, KIT, and PDGFRA. Ki67 labeling was 30%. A genetic analysis for KIT gene (exons 9, 11, 13 and 17) and PDGFRA gene (exons 12 and 18) showed no mutations. Although the differential diagnosis is problematic and difficult, the present case is probably dedifferentiated liposarcoma. The needle biopsy diagnosis of sarcomas is difficult and limited because sarcomas show heterogeneous histologies with regard to locations in the same tumor.
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PMID:CD34-positive myxoid sarcoma of the retroperitoneum: a dilemma in differential diagnosis of multiple biopsy specimens. 2055 46


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