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)

We studied the clinicopathologic and immunohistochemical features of 20 cases of proximal-type epithelioid sarcoma to identify prognostic factors. The 20 patients ranged in age from 13 to 80 years (mean, 40 y); 12 patients were male and 8 were female. The tumors presented as deep soft-tissue or subcutaneous masses on the inguinal region in five, the thigh in four, the vulva in three, the axilla in three, and one each in the flank, chest wall, back, hip and perineum. The tumors ranged from 2 to 16 cm at their greatest diameter (mean: 7.8 cm). Histologically, 12 tumors (60%) were classified as the large-cell subtype, characterized by sheets of large cells with prominent nucleoli resembling poorly differentiated carcinoma, and a frequent rhabdoid phenotype, six (30%) were classified as the conventional subtype, and two (10%) as the angiomatoid subtype. The numbers of tumors exhibiting immunoreactivity for various markers were: vimentin (20 cytokeratin (20 [100%]); epithelial membrane antigen (17 [85%]); CD34 (9 [45%]); CD99 (5 [25%]); muscle markers, either desmin or alpha-smooth muscle actin (3 [15%]), other markers such as S-100 protein, neurofilament, neuron-specific enolase, synaptophysin and CD56 (12 [60%]); and p53 (16 [80%]). Fourteen lesions (70%) exhibited an MIB-1 index of 30% or more and, by a system of histologic grading using the MIB-1 score, 16 tumors (80%) were classified as high-grade (Grade 3). Thirteen patients (65%) developed local recurrence and 15 (75%) had metastases, primarily to the lymph nodes. At the last follow-up, 13 patients (65%) had died of their disease. A large tumor size and early metastasis were independently associated with a poor outcome. We conclude that proximal-type epithelioid sarcomas are rare, undifferentiated soft-tissue sarcomas of adults, with epithelioid features and a frequent rhabdoid phenotype. These tumors, when arising in proximal locations, have a much worse prognosis than those arising in distal locations.
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PMID:Proximal-type epithelioid sarcoma: a clinicopathologic study of 20 cases. 1145 97

Reports of supernumerary ovaries are rare. We describe two such cases, one with fibroma and the other with endometriosis and cystic change. A large fibroma measuring 17.4 x 12.0 x 7.5 cm in size was found in the supernumerary ovary of the omentum in the first case of a 47-year-old married woman with Meig's syndrome. The second case was associated with endometriosis and cystic change, measuring 11 x 5 x 3 cm in size and located in the upper abdominal cavity. It was attached to the uterus of a 28-year-old pregnant woman who had neither fibroma nor Meig's syndrome. Histologically, corpus albicans and a few primordial germ cells were demonstrated, respectively. A fibroma showing a storiform pattern was found in the first case. The second case had endometriosis and a thin-walled cyst with bleeding and necrosis caused by torsion. Immunohistochemically, desmin, alpha-smooth muscle actin, c-kit, CA125, Na+/K+ATPase, overexpression of p53, myc and ras were all negative in the fibroma cells of the first case, and in the endometriosis and cyst wall of the second case. The fibroma cells were positive for vimentin and estrogen receptor, and the proliferating cell nuclear antigen was sporadically demonstrated in their nuclei. The mutation of the p53 gene at exons 5-8 was not detected by sequence analysis. Using RT-PCR, bax, bcl-2 and p16 were not detected either. Clinically, the two cases presented here did not show abnormal hormonal symptoms. They were diagnosed as abdominal tumors or masses. Based on these considerations, one might assume that supernumerary ovaries are probably more frequent than reported at present.
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PMID:Two cases of supernumerary ovary: one with large fibroma with Meig's syndrome and the other with endometriosis and cystic change. 1179 34

Gamma knife radiosurgery (RS) has been introduced as a modern therapy for brain tumors. However, the effects of RS for neuroepithelial tumors are still obscure. The present study investigates the radiological and histological changes after RS to elucidate the biological effect. There were seven cases (two males and five females), ranging from 4 to 71 years with a mean age of 33 years. Two cases were located in the brainstem, another two in the cerebellum, and one each in the thalamus, the hypothalamus, and the frontal lobe. Histologically, two cases had gangliogliomas, four astrocytomas (1 pilocytic, 1 fibrillary, 2 anaplastic), and one glioblastoma. RS was performed after surgery with a central dose of 30-36 Gy. All cases were evaluated radiologically on MRI before and after RS. Four cases (3 astrocytomas and 1 glioblastoma) which neurologically deteriorated after RS were reoperated. These cases were examined using HE and immunohistochemical studies with antibodies of CD34, alpha-smooth muscle actin (SMA), p53, p21 and MIB-1 on the sections before and after RS. MRI demonstrated perifocal edema and intratumoral hypointensity on T2 weighted imaging (T2WI), suggesting radionecrosis in most of the cases within 6 months after RS. In the central part of the RS, destructive changes were observed in the tumor cells and endothelial cells: decrease in the tumor cell population, coagulation necrosis, and fibrinoid degeneration of vascular walls were revealed. In the peripheral part, however, some tumors contained viable tumor cells intermingled with blood vessels showing endothelial and pericytic proliferations. The increase of MIB-1 staining index was found in only one case. The p21 immunoreactivity was increased in endothelial cells, although the p53 immunoreactivity was unchanged. These results suggested that radionecrosis occurred earlier and more frequently in neuroepithelial tumors after RS than after conventional radiation.
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PMID:Gamma knife radiosurgery for neuroepithelial tumors: radiological and histological changes. 1183 37

Cholestatic liver injury is caused by hepatocellular apoptosis induced by toxic bile salts. We have studied the effects of a traditional Chinese herbal medicine, Salvia miltiorrhiza, on apoptotic cell death in bile duct-ligated (BDL) rats. We also attempted to clarify the molecular mechanisms of the hepatoprotective effects of S. miltiorrhiza in this animal model. A water extract of S. miltiorrhiza (Sm-X; 200 mg/kg; po) was administered to BDL rats for 10 days. Rats were euthanized and apoptosis was detected in liver tissue by TUNEL staining. Western blot analysis and immunostaining for alpha-smooth muscle actin (alpha-SMA), Bax, Bcl-2, and p53 were performed. Results show that the treatment of BDL rats with Sm-X significantly improved the liver function parameters, although the expression of alpha-SMA, a marker of hepatic stellate cell activation, was not affected. Treatment with Sm-X significantly reduced the number of apoptotic cells. A time-dependent decrease in Bax protein level and an increase in Bcl-2 protein level were observed in BDL rats treated with Sm-X. Immunohistochemical analysis demonstrated that p53 was strongly positive in hepatocyte nuclei of BDL rats but that treatment with Sm-X induced a cytoplasmic sequestration of p53. Taken together, hepatoprotective effects of Sm-X partially ascribe to the antiapoptotic property in hepatocytes. Treatment of Sm-X-induced cytoplasmic sequestration of p53, downregulation of Bax, and upregulation of Bcl-2 protein. This study identifies and delineates signaling factors involved in the antiapoptotic properties of Sm-X and suggests a potential application of S. miltiorrhiza in the clinical management of hepatic disease induced by toxic bile salts following biliary obstruction.
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PMID:Salvia miltiorrhiza inhibits biliary obstruction-induced hepatocyte apoptosis by cytoplasmic sequestration of p53. 1212 60

The biological behaviour of a gastrointestinal stromal tumor (GIST) cannot be easily predicted from preoperative clinical examination alone. As a result, there is little standardization in the surgical treatment of GIST. In this study, we analyzed the clinicopathology and immunohistochemistry of 20 cases of GIST to clarify factors associated with tumors showing malignant potential. Immunohistochemical analysis of KIT, CD34, vimentin, alpha-smooth muscle actin (SMA), s-100, p53, ki-67, bcl-2 and bax expression was performed on 20 surgically resected GIST. An apoptotic index (AI) was calculated for each sample using a TdT-mediated dUTP-biotin nick end-labeling method. With regard to bcl-2, t(14;18) translocations were also investigated using a polymerase chain reaction based method. Finally, the relationship between these biological results and clinicopathological data was analyzed. Of the 20 cases studied, two patients died due to lung or liver metastasis. All cases stained positive for vimentin, nine cases were positive for alpha-SMA and three cases positive for s-100. All cases were stained for both KIT and CD34, which tended to correlate with malignant potential. There was significant difference in frequency of bcl-2 overexpression (p<0.05) and trend in Ki-67 labeling index (p=0.098) between benign and malignant cases. However, with regard to bcl-2, no chromosomal t(14;18) translocations were detected in four analyzed cases. In GIST, overexpression of bcl-2 may play an important role in increasing malignant potential. Furthermore, Ki-67 L.I. and bcl-2 overexpression may be useful in predicting malignant potential, and therefore help to determine the surgical treatment, follow-up manner, and the necessity of adjuvant therapy.
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PMID:Biological analysis of gastrointestinal stromal tumors. 1237 34

Activated pancreatic stellate cells (PSCs) have recently been implicated in the pathogenesis of pancreatic fibrosis and inflammation. Primary PSCs can be subcultured only several times because of their limited growth potential. A continuous cell line would be valuable in studying molecular mechanisms of these pancreatic disorders. The aim of this study was to establish an immortalized cell line of rat PSCs. PSCs were isolated from the pancreas of male Wistar rats, and the simian virus 40 T antigen was introduced to PSCs by retrovirus-mediated gene transfer. This procedure yielded an actively growing cell line, designated as SAM-K. This cell line has been passaged repeatedly for almost 2 years, and is thus likely immortalized. SAM-K cells retained morphological characteristics of primary PSCs, and expressed alpha-smooth muscle actin, glial fibrillary acidic protein, type I collagen, fibronectin, and prolyl hydroxylases. The level of p53 expression was very high in SAM-K cells. Proliferation of SAM-K cells was stimulated by serum and platelet-derived growth factor-BB. Interleukin-1beta (IL-1beta) activated nuclear factor-kappaB, activator protein-1, and three classes of mitogen-activated protein (MAP) kinases: extracellular signal-regulated kinase1/2, c-Jun N-terminal kinase, and p38 MAP kinase. IL-1beta induced expression of intercellular adhesion molecule-1 and monocyte chemoattractant protein-1, both of which were abolished in the presence of pyrrolidine dithiocarbamate, a specific inhibitor of nuclear factor-kappaB activation. IL-1beta-induced monocyte chemoattractant protein-1 was partially inhibited by specific inhibitors of MAP kinase kinase (U0126) and of p38 MAP kinase (SB203580) whereas intercellular adhesion molecule-1 expression was not altered by the inhibitors. Thus, SAM-K would be useful for in vitro studies of cell biology and signal transduction of PSCs.
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PMID:Establishment and characterization of a simian virus 40-immortalized rat pancreatic stellate cell line. 1249 15

Leiomyomatosis peritonealis disseminata (LPD) is a rare clinicopathological entity typically observed in women of reproductive age. We report a case of LPD with malignant change in a man. A 77-year-old man presented with a mass measuring 10 cm in diameter at the terminal ileum and numerous peritoneal small nodules that were revealed by abdominal computed tomography. Right hemicolectomy with lymph node dissection was performed. Macroscopically, a tumor of the terminal ileum consisted of aggregates of small nodular lesions with calcification and necrosis. The wall of the ileum and colon was intact. Microscopically, some of the nodular lesions consisted of neoplastic growths of atypical spindle cells with cellular atypism and abnormal mitoses. A few of these lesions were completely surrounded by smooth muscle bundles. Hemorrhages and necroses were found within the tumor nodules. Immunohistochemically, the tumor cells were positive for vimentin, desmin, muscle actin, alpha-smooth muscle actin, cytokeratin and p53. The remaining nodular lesions, including small peritoneal lesions, were composed of hypocellular hyalinizing nodules. This case was thought to be LPD with malignant change, although the pathogenesis was uncertain because the tumor cells were negative for estrogen and progesterone receptors.
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PMID:Leiomyomatosis peritonealis disseminata with malignant change in a man. 1260

We report an unusual case of spindle epithelial tumor with thymus-like differentiation (SETTLE) of the thyroid present in a 6-year-old boy. The tumor, located at both the left lobe and isthmus, was a circumscribed mass with slightly gritty whorled appearance. Microscopically, the lobulated, highly cellular, spindle cell neoplasm was arranged in intersecting bundles and fascicles separated by fibrous bands. Benign-appearing glands entrapped within fibrous bands and foci of squamous differentiation within spindle cells were observed. Immunohistochemically, the spindle cells were diffusely positive for cytokeratins, vimentin, and alpha-smooth muscle actin and patchily reactive for muscle-specific actin and epithelial membrane antigen, exhibiting myoepithelial differentiation. The spindle cells were also patchily immunopositive for p53 protein. Molecular genetic analysis revealed Ki-ras gene mutations at codons 13 (GGC(gly) to AGC(ser)) and 15 (GGC(gly) to AGC(ser)) on the same allele. Mutation of the p53 gene was not detected. This is the first report on Ki-ras oncogene mutations in a case of SETTLE.
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PMID:Spindle epithelial tumor with thymus-like differentiation of the thyroid: a case report with pathological and molecular genetics study. 1261 89

Several immunohistochemical markers have been used to demonstrate the presence of myoepithelial cells in order to determine their role in the histogenesis of mammary tumors. p63, a recently characterized p53 homologue, is consistently expressed in myoepithelial cells of the human breast; however, no assessment of its immunoreactivity has been reported so far in canine mammary tissues. We investigated p63 immunohistochemical expression, as a novel myoepithelial cell nuclear marker, in 81 samples of normal (n = 2), hyperplastic (n = 11), and neoplastic (n = 68) canine mammary tissues. Myoepithelial phenotype was confirmed by using complementary monoclonal antibodies: alpha-smooth muscle actin, cytokeratin 14, cytokeratin AE1/AE3, and vimentin. p63 expression was observed in 91.4% (74/81) of the samples evaluated. Normal mammary glands, mammary hyperplasias, and benign tumors showed 100% immunoreactivity, with p63 expression restricted to myoepithelial cell nuclei. In general, benign mixed tumors showed a basal cell compartment immunoreactive to p63, with a gradual decrease of its expression during myoepithelial transformation. p63 expression was found in 72% of malignant tumors, allowing myoepithelial or basal cell identification in spindle-cell carcinomas (2/2), tubulopapillary carcinomas (8/9), solid carcinomas (7/10), and carcinosarcomas (1/3). The osteosarcoma analyzed was p63 negative. In our series, stromal components were consistently nonreactive to p63. In conclusion, the present study reveals p63 as a sensitive and highly specific marker of myoepithelial cells in canine mammary tissues, and the authors suggest p63 as an additional marker for defining myoepithelial histogenesis.
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PMID:p63: a novel myoepithelial cell marker in canine mammary tissues. 1282 13

We report the clinicopathologic findings of four cases of liposarcoma with meningothelial-like whorls. Two cases occurred in the retroperitoneum and the remaining cases in the anterior mediastinum and scrotum. The whorls varied in terms of amount and morphology and the type tissue surrounding the whorls also varied in every case. One of the retroperitoneal cases with large areas of whorl coalescence recurred in the abdominal wall as an inflammatory malignant fibrous histiocytoma one year after primary resection of the tumor, and a metastasis to the cervical spines was detected twenty months later. The other retroperitoneal tumor recurred locally two years after the resection of the tumor and the amount and cellularity of the whorls as well as p53 reactivity and Ki-67 labeling index were higher in the recurrent tumor. However, coalescence of the whorls was not present in the recurrent tumor in contrast to the primary tumor. The anterior mediastinal and scrotal cases have demonstrated neither local recurrence nor distant metastasis although the follow-up period has been less than one year. The cells comprising whorls showed positive reactions for CD10, CD56, CD99, factor XIII, and low-affinity nerve growth factor receptor in addition to vimentin and alpha-smooth muscle actin. Our results indicate that liposarcoma with meningothelial-like whorls is a heterogeneous group that shows wide variations in histologic findings and biologic behavior. The phenotypic transformation of the whorls to higher grade in two retroperitoneal tumors, which showed recurrence within two years of follow up, supports that a whorl is a sign of dedifferentiation. Although we demonstrate the expressions of several markers, such as CD10, CD56, CD99, factor XIII, and low-affinity nerve growth factor receptor, in the spindle cells of the whorls for the first time, the lineage of the whorls still cannot be addressed due to the fact that these markers are lineage nonspecific.
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PMID:Liposarcoma with meningothelial-like whorls. Report of four cases showing diverse histologic findings and behavior. 1283 76


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