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)

To broaden the knowledge of myxoid morphology in liposarcoma, eight cases of unusual liposarcoma with combined well-differentiated and myxoid malignant fibrous histiocytoma (MFH)-like myxoid areas are reported. The tumors arose as huge retroperitoneal masses in elderly patients, except for one that occurred in the spermatic cord. Three cases had local recurrences, and one of the seven patients who were followed up had died of the tumor. Grossly, the tumors were mostly confluent and multinodular and showed a glistening myxoid appearance in variable proportions, which merged gradually into or were juxtaposed to yellow fatty or sclerotic whitish areas. Microscopically, in addition to areas of well-differentiated lipoma-like or sclerosing liposarcoma, all the tumors contained myxoid portions characterized by scattered multinucleated or bizarre giant cells and a prominent plexiform vascular pattern that resembled myxoid MFH or myxofibrosarcoma. The myxoid areas were associated with discernible lipogenesis. High-grade dedifferentiation was present in one tumor. Cytogenetically, in one case, the myxoid lesion had nonrandom chromosomal aberrations, such as ring and marker chromosomes, characteristic of a well-differentiated variant of liposarcoma. In a nested reverse transcription-polymerase chain reaction analysis using archival paraffin-embedded tissue, it was seen that none of the eight tumors with myxoid MFH-like features had TLS/FUS-CHOP fusion transcripts characteristic of myxoid and round cell liposarcomas. These clinicopathologic and molecular features suggest that the current myxoid tumors are more closely related to well-differentiated liposarcoma rather than to ordinary myxoid liposarcoma despite their unequivocal myxoid morphology. Missense point mutations of the p53 gene were detected in two (25%) cases by single-strand conformation polymorphism and sequence analyses. Immunohistochemical expressions of p53 and mdm2 were observed in 75% of the cases, in which immunoreactive tumor cells were seen more often in the myxoid MFH-like areas. Thus, altered p53 pathways, such as p53 gene mutation and mdm2-mediated inactivation of p53, may play a pathogenetic role in this form of tumor progression showing myxoid MFH-like morphology in liposarcoma, as has been suggested in dedifferentiated liposarcoma.
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PMID:Retroperitoneal liposarcoma with combined well-differentiated and myxoid malignant fibrous histiocytoma-like myxoid areas. 1058 1

A mixed myxoid/round cell liposarcoma was macrodissected in its 2 histologic components and investigated for genetic differences between its low-grade myxoid and the high-grade round-cell region. For both, we failed to detect p53 gene mutations, loss of heterozygosity at the p53 or Rb genes, and p53 protein expression. The round-cell component showed a high telomerase activity, and an elevated c-myc mRNA and protein expression. The myxoid component was characterized by a lack of telomerase activity and low c-myc mRNA expression, and immunohistochemistry failed to detect the c-myc protein. There was a higher Mib-1 proliferation index in the round-cell portion. The same specific translocation t(12;16) and the fusion transcript type II in both components confirmed the close relationship between myxoid and round-cell liposarcomas. Telomerase activity and increased c-myc expression seem to be helpful molecular markers for characterizing tumor progression in myxoid liposarcoma.
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PMID:Myxoid liposarcoma with transition to round-cell lesion-cell cycle regulator genes and telomerase activity characterizing tumor progression: a case report. 1066 32

A novel cell line, named LSA, has been obtained, stabilized, and characterized from a human liposarcoma. These cells have morphological and biochemical features strongly resembling the adipocytes and were able to grow in the Ham's F12 medium, in presence or absence of FCS. A conditioned medium (LSA-CM) was obtained by growing the LSA cells in the F12 medium in the absence of FCS. LSA-CM had cytostatic and cytotoxic effects (apoptosis and necrosis) associated with down-regulation of c-myc and upregulation of p53 in several human cell lines (breast, lung, glioblastoma, etc. ). The MCF-7 and glioblastoma cells were killed by LSA-CM in 5-6 days, whereas the same cells were killed by LSA-CM co-incubated with low doses of cisplatin in 30 h. LSA-CM peri-tumoral injections for 15 days in Balb-c-fc3H mice affected by mammary tumors, resulted in the rapid disruption of tumors and absence of metastases. In contrast, in the untreated animals the tumor masses were 4 times larger than initial lesions, and numerous metastases were found in the lungs. The toxicity analysis of LSA-CM, performed on three different animal species, showed that LSA-CM is absolutely free of acute, subacute, and subchronic toxicity. The possible use of LSA-CM/cisplatin for cancer treatment is discussed.
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PMID:A conditioned medium from a human liposarcoma-derived cell line induces p53-dependent apoptosis in several tumor cell lines. 1076 81

The purpose of this study was to obtain further information regarding cellular differentiation and proliferative characteristics of dedifferentiated liposarcoma (DDL) arising in the retroperitoneum and mesentery for accurate diagnosis and prognostic criteria. The patients included 20 men and 12 women, mean age, 60 years (range, 33 to 80 years). Twenty-seven tumors were located in the retroperitoneum and 5 in the mesentery. Tumor size ranged from 9 to 51 cm (mean, 24 cm). Follow-up was available on all patients and ranged from 4 to 243 months (mean, 64 months). Twenty-four (75%) patients developed local recurrences, 3 (9%) had distant metastasis, and 16 (50%) died of the disease. The predominant histology of dedifferentiation (DD) included fibrosarcoma or malignant fibrous histiocytoma (MFH) in 15 (47%), myxofibrosarcoma (myxoid MFH) in 5 (16%), mixed type in 10 (31%), and a whorling pattern in 2 (6%). Divergent differentiation, such as osseous, osteosarcomatous, chondrosarcomatous, and leiomyosarcomatous, was observed in 9 (28%). Immunoreactivity for vimentin, desmin, CD34, neurofilament, alpha-smooth muscle actin, p53, and MDM2 was observed in 32 (100%), 14 (44%), 8 (25%), 13 (41%), 14 (44%), 19 (59%), and 18 (56%) of DD areas, respectively. On the basis of a histological grading using MIB-1 (MIB-1 index range, 3% to 80%; mean, 27%) to replace mitosis counts (1 to 35/10 high-power fields [HPF]; mean, 13/10 HPF), 16 tumors each were classified as low-grade (grade 2) and high-grade (grade 3). The mixed type with poorly differentiated areas including scattered lipoblasts could be mistaken for myxoid liposarcoma but lacked the C/EBP-homologous protein-translocated in liposarcomat (CHOP-TLS) fusion genes specific for myxoid liposarcoma. Period to the first recurrence and histological grade using the MIB-1 index were associated with overall survival. Identification of DD areas, especially a poorly recognized variant of the mixed type, careful follow-up to detect early recurrence, and histological malignancy grading combined with proliferation indices are important in providing an accurate prognosis for all patients with retroperitoneal and mesenteric liposarcoma.
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PMID:Dedifferentiated liposarcoma of retroperitoneum and mesentery: varied growth patterns and histological grades--a clinicopathologic study of 32 cases. 1087 66

MDM2 gene is overexpressed in several tumors and its product may be processed into different isoforms, some of which have been demonstrated to possess transforming activity. In a panel of liposarcomas characterized by displaying 4 different combinations of mdm2/p53 immunoreactivity, molecular analysis of amplified MDM2 gene revealed a coexistence of mutated full-length MDM2 messenger RNAs, an out-of-frame splicing mRNA and finally aberrant spliced forms. Two of the latter are reported here for the first time. The molecular differences in this heterogeneous mRNA population seem to mirror distinct functional aspects of the altered encoded mdm2 proteins. In fact, besides the deleted transcripts defective in their ability to bind p53 and known to possess a transforming activity, here we describe both mutated full-length forms and deleted transcripts that still maintain the ability to bind p53 but, based on their mdm2+/p53+ immunophenotype, probably fail to signal its degradation. These aberrant forms, which are responsible for the accumulation and inactivation of p53, can contribute, together with the p53 independent transforming forms, to liposarcoma transforming pathway.
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PMID:Analysis of the molecular species generated by MDM2 gene amplification in liposarcomas. 1135 Dec 97

Alteration of the p53/mdm2 pathway has been reported in the well-differentiated liposarcoma (WDLS)/dedifferentiated liposarcoma (DDLS) group. We investigated the immunoreactivity of p53, mdm2, and p21WAF1, along with the MIB-1-labeling index (MIB-1-LI) in 21 WDLS and 21 DDLS cases, to clarify the association of these markers with the morphologic changes and the biological factors responsible for the aggressiveness of DDLS. Within DDLS, p53 and p21WAF1 expression and mdm2 overexpression were significantly more prevalent in the dedifferentiated (DD) components than in the well-differentiated (WD) components. The mdm2 overexpression and p21WAF1 expression was significantly associated with sclerosing liposarcomas in both WDLS and the WD components of DDLS. There was no significant difference in the immunoreactivity of p53, mdm2, or p21WAF1 or MIB-1-LI between WDLS and the WD components of DDLS. An association was found between p53 expression and mdm2 overexpression in the WD group (comprising WDLS and WD components of DDLS) and in the DD group, significantly so in the WD group. Notably, this correlation was found in the subtype of sclerosing liposarcoma but not in that of lipoma-like liposarcoma. Within DDLS, the clinical outcome of the nonaccessible soft tissue (non-AST: comprising retroperitoneum and mediastinum) group was significantly worse than that of the accessible soft tissue (AST: comprising extremities, buttocks, axilla, and scrotum) group; however, the immunophenotypes of p53, mdm2, and p21WAF1 and the MIB-1-LI showed no correlation with survival in the AST group alone, in the non-AST group alone, or in the 2 together. This study suggests that the immunoreactivity of p53, mdm2, and p21WAF1 is associated with the morphologic changes, but not with the biological factors responsible for the aggressiveness of DDLS.
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PMID:Immunoreactivity of p53, mdm2, and p21WAF1 in dedifferentiated liposarcoma: special emphasis on the distinct immunophenotype of the well-differentiated component. 1148 9

We investigated a lipoma and a well-differentiated/dedifferentiated liposarcoma (WD/DDL), occurring simultaneously in one patient for the possible role of p53 and mdm2 in the molecular oncogenesis of liposarcoma and tumor progression. The hypothesis tested was if there is a continuum in the development from lipoma to liposarcoma. Lipoma was characterized by a lack of p53 mutation, p53 LOH and p53 protein expression, as well as by mdm2 amplification and mdm2 protein expression. p53 mutation and p53 LOH were found neither in the well-differentiated nor in the dedifferentiated parts of the liposarcoma. In contrast, mdm2 amplification and an increase in mdm2 protein expression were found to be associated with malignancy and dedifferentiation, whereas p53 protein expression was only slightly increased. These findings indicate that mdm2 constitutes one of the most common targets for molecular aberration in WD/DDL. We suggest that mdm2 is a marker distinguishing between ordinary lipoma and well-differentiated liposarcoma, and that the genesis of these tumors is different.
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PMID:Distinction between lipoma and liposarcoma by MDM2 alterations: a case report of simultaneously occurring tumors and review of the literature. 1151 50

The cytotoxic effects of ecteinascidin-743(ET-743), a novel marine natural product, were evaluated and compared with that of clinically used anticancer agents methotrexate, doxorubicin, etoposide, and paclitaxel in eight human soft tissue sarcoma (STS) cell lines. HT-1080, a fibrosarcoma cell line, and HS-42, a malignant mesodermal cell line, were the most sensitive of the cell lines to methotrexate, doxorubicin, etoposide, and paclitaxel. Other cell lines (IC50s) varied considerably and were more resistant to these agents. ET-743 was more potent than any of these agents, with IC50s in the pM range in all of the cell lines. Cytotoxicity of ET-743 was dose- and time-related (4-72 h exposure). Cytotoxic concentrations of ET-743 produced a S/G2 block in all of the cell lines tested. Three colon adenocarcinoma cell lines, HCT-8, HT-29, and HCT-116, and one breast cancer cell line, MCF-7, were 1-2 logs less sensitive to ET-743 than the STS cell lines. Cell lines were also characterized as to expression of oncogenes and tumor suppressor genes to attempt to correlate sensitivity of these cell lines to ET-743 and other chemotherapeutic agents. All of the cell lines except M8805, a malignant fibrous histiocytoma cell line, had mutations in p53 and/or overexpressed the MDM2 protein. Only HS-18, a liposarcoma cell line, lacked expression of the retinoblastoma protein. None of the cell lines had detectable expression of P-glycoprotein as measured by immunohistochemistry. ET-743 is an extremely potent cytotoxic agent against human STS cell lines and is being evaluated as an antitumor agent in this disease.
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PMID:Sensitivity of soft tissue sarcoma cell lines to chemotherapeutic agents: identification of ecteinascidin-743 as a potent cytotoxic agent. 1155 9

A number of human cell lines derived from well-differentiated, myxoid/round cell, or pleomorphic liposarcoma have been described. To our knowledge, however, no human cell line established from dedifferentiated liposarcoma has been reported. In this study, we established a new human cell line, FU-DDLS-1, which originated from a dedifferentiated liposarcoma arising in the retroperitoneum of a 61-year-old man. This cell line was characterized by immunocytochemistry, conventional banding analysis, fluorescence in situ hybridization with chromosome painting probe, and comparative genomic hybridization (CGH). FU-DDLS-1 cells were spindle or polygonal shaped and possessed oval nuclei and slender cytoplasmic processes. The cultured cells were successfully maintained in vitro for over 90 passages over more than 30 months. The histologic features of heterotransplanted tumors in severe combined immunodeficiency mice were essentially the same as those of the original nonlipogenic sarcoma resembling a malignant fibrous histiocytoma. Both in vitro and in vivo, the cells exhibited immunopositive reaction for mdm2 and p53 proteins. Cytogenetically, FU-DDLS-1 displayed a hypertetraploid karyotype with giant marker chromosomes composed partly of chromosome 12 material. In addition, CGH analysis demonstrated that DNA sequence copy number changes including a gain of 12q12-q21 detected in FU-DDLS-1 were essentially the same as those in the original sarcoma. The FU-DDLS-1 cell line, which exhibits the unique conventional and molecular cytogenetic characteristics of dedifferentiated liposarcoma, should be a particularly useful model for studying the molecular pathogenesis of human dedifferentiated liposarcoma.
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PMID:Establishment of a novel human dedifferentiated liposarcoma cell line, FU-DDLS-1: conventional and molecular cytogenetic characterization. 1257 6

The term "malignant mesenchymoma" (MM) has traditionally been applied to a group of malignant soft tissue tumors that are characterized by the presence of two or more different mesenchymal tissue components in the same neoplasm. Currently, sarcomas with multilineage differentiation fulfilling the criteria of MM tend to be diagnosed as specific sarcomas with heterologous differentiation (e.g., de-differentiated liposarcoma) rather than MM; however, some cases of these tumors are difficult to classify. The purpose of this study was to analyze the clinicopathological and immunohistochemical features of these unclassifiable tumors, the so-called MM, and to determine whether some parameters are a useful adjunct for the classification of these tumors from the viewpoint of clinical outcome. Twelve cases of so-called MM were investigated retrospectively. The patients (six male, six female) ranged in age from 6 to 71 years (mean 48 years). Tumor size ranged from 3 to 20 cm (mean 13 cm). Tumor locations included the retroperitoneum (five cases), abdominal wall (two), thigh (two), forearm (one), lung (one), and parotid gland (one). The differentiated mesenchymal components were rhabdomyosarcomatous (RMS) (six cases), liposarcomatous (five), chondrosarcomatous (five), osteosarcomatous (five), or leiomyosarcomatous (four). Follow-up in all cases (range 4-129 months; mean 36 months) showed a 67% local recurrence rate, a 33% metastatic rate, and a 50% disease-related mortality. The patients who were under 40 years of age or who had an RMS component showed significantly worse survival than did patients in the other groups. The other mesenchymal components showed no significant correlation with survival. The immunophenotypes of p53 and mdm2 were almost identical between the two mesenchymal components in each case; however, there was no significant correlation between either of these immunophenotypes and the clinical outcome. None of the other factors (gender, tumor site, tumor size, or MIB-1-labeling index) was found to be a statistically significant prognostic indicator. In conclusion, a patient age under 40 years and the presence of an RMS component appear to be poor prognostic indicators of survival in patients with so-called MM, and to be a useful adjunct for the classification of these tumors.
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PMID:Prognostic factors in the so-called malignant mesenchymoma: a clinicopathological and immunohistochemical analysis. 1279 27


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