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 present a unique carcinoma of the pancreas with predominantly clear cell morphology (>95% clear cells). Mucicarmine stain revealed abundant intraluminal and intracytoplasmic mucin. Immunohistochemically, the cells were positive for the epithelial markers cytokeratin 7 and CAM 5.2, and were focally positive for cytokeratin 20. These cells also expressed monoclonal carcinoembryonic antigen. Stains for the neuroendocrine markers synaptophysin and chromogranin were negative, as were stains for vimentin, p53, HMB-45, and CD10. An additional outstanding feature was the presence of dense intraluminal and intracytoplasmic hyaline globules, which were immunohistochemically positive for alpha1-antitrypsin. Sequencing of the K-ras oncogene revealed a point mutation in codon 12, providing molecular evidence of ductal origin. In the proper morphologic context supported by immunohistochemistry, clear cell carcinoma can be regarded as a rare variant of ductal adenocarcinoma.
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PMID:Clear cell ductal adenocarcinoma of pancreas: a case report and review of the literature. 1516 26

Malignant cell proliferation and accumulation depends on the balance between the rates of cell production and cell death. Recent evidence indicates that apoptosis is important in the development of cancer. Apoptosis is strictly controlled by various regulators, which can take part in the apoptotic process, proliferation and differentiation alike. Apoptosis was induced in myeloid cell line ML-2 by camptothecin, an inhibitor of topoisomerase I. After 18 hours of induction by camptothecin 50% of cells were apoptotic. The apoptotic effect of CAM was reversible in the cells studied. The induction of apoptosis influenced the expression of apoptosis and cell cycle regulators as detected by cDNA arrays, RT-PCR or Western blotting. According to cDNA arrays e.g. bax, bfl1, bak, pRb2, c-jun, jun-B were upregulated, and cdk4, cyclin B1, wee1, CRAF1, DP1 were downregulated. A number of other regulators like p21 and cdc25A, as well as some other genes linked with apoptosis, as p53 and the bcl-2 family, were up- or down-regulated as determined by real-time PCR. Changes in gene expression were found not only in the group of regulators of apoptosis and the cell cycle, but also among regulators of differentiation.
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PMID:Gene expression during camptothecin-induced apoptosis in human myeloid leukemia cell line ML-2. 1525 69

We investigated the mechanism of inhibition of cell proliferation by mixed isomers of CLA (9-cis, 11-trans CLA; 10-trans, 12-cis CLA) on human, non-tumorigenic MCF10A cells that were derived from mammary ductal epithelial cells and MCF7 cells that were derived from a well differentiation mammary adenocarcinoma. When treated in the log phase of growth, the uptake of CLA by MCF7 exceeded the levels measured in MCF10A cells. Treatment with CLA in the presence of HPO doubled the incorporation of CLA in MCF7 cells, independent of the isomer, but reduced the incorporation of CLA by MCF10A cells. CLA caused tumor cell-targeted increased expression of 4-hydroxy-2-nonenal (4HNE), a product of lipid peroxidation, and decreased proliferation in MCF7 cells, as measured by the incorporation of bromodeoxyuridine (BrdU) and expression of phosphorylated histone H3, and the effects of CLA in combination with HPO on mitosis were greater than the effects of either agent alone. Decreased cell proliferation in CLA-treated MCF7 cells coincided with increased nuclear localization of phosphorylated, activated p53 protein, and decreased nuclear localization of the transcription factor FKHRSer256. Importantly, CLA-treated MCF7 cells were more sensitive than MCF10A cells to HPO-induced 4HNE, expression of p53, and decreased mitotic activity. These studies suggest that tumor cell-targeted increased sensitivity to oxidative stress and activation of p53 play important roles in the regulation of human breast cancer cell proliferation by CLA.
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PMID:Breast cancer cell-targeted oxidative stress: enhancement of cancer cell uptake of conjugated linoleic acid, activation of p53, and inhibition of proliferation. 1599 97

Currently available clinico-pathologic criteria provide an imperfect assessment of outcome for patients with advanced epithelial ovarian cancer (EOC). Identification of prognostic factors related to tumor biology might improve this assessment. We investigated the prognostic significance of the melanoma cell adhesion molecule (M-CAM) in EOC. Using the same antibody, M-CAM expression was tested by Western blotting in protein extracts and by immunohistochemestry in tissue microarrays generated from 133 consecutively resected, well characterized EOC samples. Fisher test, Kaplan-Meier method and Cox proportional hazards analysis were used to relate M-CAM expression to clinico-pathological variables and to time to progression (TTP) and overall survival (OS). In vitro biochemical analysis showed a progressively increased M-CAM expression from normal to malignant cells. M-CAM protein, detected immunohistochemically, was significantly associated with advanced tumor stage, serous and undifferentiated histotype, extent of residual disease and p53 accumulation. Presence or absence of M-CAM significantly divided patients according to their TTP (median, 22 vs. 79 months, respectively; log-rank p = 0.001) and OS (median, 42 vs. 131 months, respectively; log-rank p = 0.0003). In the subgroup of advanced stage patients who achieved complete response after front-line treatment, M-CAM expression and absence of residual disease were significantly associated with shorter TTP (p = 0.003, HR 5.25, 95% Cl 1.79-15.41 and p = 0.011, HR 3.77, 95% Cl 1.36-10.49 respectively) at the multivariate level. In the same sub-group of patients, M-CAM expression remained the only parameter significantly associated with OS (p = 0.005, HR 3.35, 95% Cl 1.42-6.88). M-CAM is a marker of early relapse and poorer outcome in EOC. In particular, M-CAM expression identifies a subgroup of front-line therapy-responding patients who undergo dramatic relapses, thus helping to better select patients who might benefit from new/alternative therapeutic modalities.
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PMID:M-CAM expression as marker of poor prognosis in epithelial ovarian cancer. 1680 6

We report a cribriform carcinoma of the left fossa poplitea in a 62-year-old woman. The patient did not present any symptoms, and the only complaint was the nodule, which was resected for diagnosis. After considering different diagnostic options, we decided that the most appropriate one was cribriform carcinoma, which is an entity described in 1998. The diagnostic criteria, which were provided in the few publications that refer to this entity, helped us to distinguish it from the main mimicker: cystic adenoid carcinoma. Owing to the cribriform pattern of the tumor, we also looked for a metastasis from other sites, mainly breast, vulva, and salivary glands, but all these were clinically excluded. The tumoral cells showed secretion by decapitation, as well as a positive stain of the luminal secretion by histochemical techniques of Alcian blue and periodic acid-Schiff. The tumor was negative for iron stain. In spite of these characteristics, which are, for some authors, indicative of an apocrine phenotype, the immunohistochemical study revealed some differences with the profile that has been described in cases of apocrine adenocarcinoma. The tumor did not express GCDFP-15 or CD 15. It was also negative for SMA, CEA, and PR. The pattern of cytokeratins expressed by our case was positive for AE1-AE3, CAM 5.2, and CK7, without any expression for CK20. Other markers expressed by the tumor were EMA, ER, c-erbB-2, p53, and S-100.
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PMID:Immunohistochemical phenotype of cutaneous cribriform carcinoma with a panel of 15 antibodies. 1808 81

We present the surgical and pathological findings and follow-up of 5 women diagnosed with combined endometrioid and high-grade neuroendocrine carcinoma of large cell type (LCNEC) arising in the endometrium. The mean age of the women was 75 years (range, 50-88 years). Of the 5 tumors, 4 formed polypoid endometrial masses associated with extensive lymphovascular involvement of the myometrium by neoplastic cells. A single endometrial tumor was formed by LCNEC alone, and 4 tumors were composite with varying proportions formed by endometrioid (4/5) and small cell neuroendocrine carcinoma (1/5). In all 5 LCNEC tumor components, an insular growth pattern was noted, whereas a diffuse (solid) pattern was found in 4 tumors, a trabecular in 2, and rosettes/pseudorosettes in another 2. In all 5 tumors, the LCNEC tumor components were labeled with neuron-specific enolase (NSE). Four tumors were reactive for chromogranin A, CAM 5.2, and p53. Three tumors were labeled for AE1/AE3, CD56 (NCAM), p16, and cytokeratin 7. Synaptophysin was reactive in 2 tumors, and CD117 was found in only a single tumor. Of the 3 endometrioid tumor components examined, all were reactive for NSE. Two tumors were reactive for p16 and p53, 1 for CD56, but none for synaptophysin orchromogranin A. We conclude that LCNEC of the endometrium is a distinct clinicopathological entity with a poor prognosis irrespective of stage. The gross and histomorphological features are often suggestive, but confirmation requires immunoperoxidases, including NSE, synaptophysin, chromogranin A, p16, and p53. Combined endometrioid and high-grade LCNEC possess more characteristics of a type II than a type I endometrial carcinoma.
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PMID:Combined large cell neuroendocrine and endometrioid carcinoma of the endometrium. 1815 75

Carcinosarcomas are malignant tumors with a mixture of carcinomatous and differentiated sarcomatous elements. We investigate the morphology, immunohistochemistry, and comparative genomic hybridization analysis of 3 mixed squamous carcinoma and osteosarcoma of the lung. All patients were male and their ages were 72, 43, and 58 years. The sizes of the neoplasms were 7, 5, and 5 cm in maximum diameter, respectively. Two patients died of the disease 9 and 14 months after surgery; and one is alive 6 months later. By light microscopy, all cases had both squamous and osteosarcomatous structures. Immunohistochemistry was positive for AE3AE1, p63, 34 E12, CAM 5.2 (2/3 cases), CK-7 (2/3 cases), epithelial membrane antigen, E-cadherin, p53, and carcinogenic embryonic antigen in carcinomatous areas, and for vimentin and CD-68 in sarcomatous component. Areas of transition positive for both cytokeratins and vimentin were seen in all cases. A total of 55 copy number changes were detected with a median of 18 abnormalities per case: 48 gains, 6 losses, and 1 high-level amplification. Chromosome alterations in osteosarcomatous areas were similar to those found in lung metastatic osteosarcoma, comparable to those found in carcinomatous areas and to lung squamous carcinomas. Coincidences between carcinomatous areas and osteosarcomatous zones were found as gains in chromosomes 1q, 3q, 5p, 8q, and 12p. These findings provide arguments that favor a common origin for both types of cells, supported by the mixture of cells, the existence of undifferentiated cells positive to both cytokeratin and vimentin markers, and the CGH overlaps of chromosomal gains between carcinomatous and sarcomatous areas.
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PMID:Primary mixed squamous carcinoma and osteosarcoma (carcinosarcomas) of the lung have a CGH mapping similar to primitive squamous carcinomas and osteosarcomas. 1838 57

The growth inhibitory effect of a mixture of trans, trans conjugated linoleic acid isomers (t, t CLA) was investigated in a human breast cancer cell line, MCF-7, with references to c9, t11 CLA, t10, c12 CLA, and linoleic acid. The t, t CLA treatment effectively induced a cytotoxic effect in a time-dependent (0-6 days) and concentration-dependent (0-40 microM) manner, as compared to the reference and control treatments. The apoptotic parameters were measured on cells treated with 40 microM t, t CLA for 4 days. The occurrence of the characteristic morphological changes and DNA fragmentation confirmed apoptosis. The t, t CLA treatment led to an increase in the level of p53 tumor suppressor protein and Bax protein, but suppressed the expression of Bcl-2 protein. In addition, cytochrome c was released from the mitochondria into the cytosol, and the activation of caspase-3 led to the cleavage of poly(ADP-ribose) polymerase (PARP). Moreover, the composition of the linoleic and arachidonic acids was decreased in cellular membranes. These findings suggest that incorporation of t, t CLA in the membrane induces a mitochondria-mediated apoptosis that can enhance the antiproliferative effect of t, t CLA in MCF-7 cells.
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PMID:A mixture of trans, trans conjugated linoleic acid induces apoptosis in MCF-7 human breast cancer cells with reciprocal expression of Bax and Bcl-2. 1857 Apr 28

The anticarcinogenic activity of a mixture of trans,trans-conjugated linoleic acid (trans,trans-CLA) was investigated in rat mammary tumorigenesis induced by N-methyl-N-nitrosourea (MNU), with references to cis-9,trans-11-CLA and trans-10,cis-12-CLA isomers. Female, 7-week-old Sprague-Dawley rats were intraperitoneally injected with MNU (50 mg/kg of body weight) and then subjected to one of five diets (control, 1% trans,trans-CLA, 1% cis-9,trans-11-CLA, 1% trans-10,cis-12-CLA, and 1% linoleic acid; 8 rats/group) for 16 weeks. Food and water were made available ad libitum. trans,trans-CLA significantly (p < 0.05) reduced tumor incidence, number, multiplicity, and size and significantly (p < 0.05) increased apoptosis, relative to cis-9,trans-11-CLA and trans-10,cis-12-CLA. The molecular mechanism of trans,trans-CLA was elucidated by measuring apoptosis-related gene products and fatty acid composition in tumors. trans,trans-CLA led to increases in the p53 protein and Bax protein levels but suppressed the expression of Bcl-2 protein. The activation of caspase-3 led to the cleavage of poly(ADP-ribose) polymerase, which resulted in the execution of apoptosis. In addition, trans,trans-CLA reduced cytosolic phospholipase A2, cyclooxygenease-2, and peroxisome proliferator-activated receptor gamma protein levels. These results suggest that the trans,trans-CLA inhibits MNU-induced rat mammary tumorigenesis through the induction of apoptosis in conjunction with the reduction of arachidonic acid metabolites and that the efficacy of trans,trans-CLA is superior to cis-9,trans-11-CLA and trans-10,cis-12-CLA.
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PMID:Superior anticarcinogenic activity of trans,trans-conjugated linoleic acid in N-methyl-N-nitrosourea-induced rat mammary tumorigenesis. 2037 64

We present the clinicopathological features of eight cases of large cell undifferentiated bladder carcinoma not otherwise specified (LCUBC). LCUBC was characterised by sheets of large polygonal or round cells with moderate to abundant cytoplasm and distinct cell borders. The LCUBC component varied from 90 to 100% of the tumour specimen with five cases showing pure LCUBC. The architectural pattern of the tumour varied from infiltrating tumour to solid expansile nests with focal (<5%) discohesive growth pattern in two cases. Immunohistochemical staining demonstrated that LCUBC cases were positive for cytokeratins AE1/AE3 and 7; CAM 5.2, CK20, thrombomodulin and uroplakin III were positive in six, three, three and two cases, respectively. Other immunohistochemical markers performed in the differential diagnosis context included alpha-fetoprotein, beta human chorionic gonadotrophin (betahCG), prostate specific antigen (PSA), vimentin, synaptophysin and chromogranin and all were negative. Ki-67 and p53 labelling indexes were 50-90% and 40-90%, respectively. All patients had advanced stage cancer (>or=pT3) and seven (87.5%) had lymph node metastases. Follow-up information was available in all cases, with a range of 6-26 months (mean 10.6 months). Six patients died of disease between 5 and 26 months and two patients were alive with metastases at 6 and 14 months. The prognosis of LCUBC was compared with conventional urothelial carcinoma of similar stages showing survival differences (p =0.0004). In summary, LCUBC is an aggressive variant of urothelial carcinoma that presents at an advanced stage.
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PMID:Large cell undifferentiated carcinoma of the urinary bladder. 2043 10


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