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)

The objective of this study was to compare the immunohistochemical profile and clinical course of primary peritoneal serous carcinoma (PPC) and primary ovarian serous carcinoma (OSC). These entities are virtually indistinguishable morphologically, but their differential molecular and clinical features are incompletely characterized. Twenty-nine cases of high-grade, high-stage PPC and 96 cases of stage matched OSCs were compared. PPC was identified based on the criteria proposed by the Gynecologic Oncology Group. The tumors were staged according to International Federation of Gynecology and Obstetrics criteria for ovarian cancer and graded according to World Health Organization criteria. Expression of Cox-2, CD-34, bcl-2, and p53 was compared in the two tumors and correlated with clinical data including stage, age, race, and overall survival. Although the median survival, using Kaplan-Meier test, of patients with OSC (1060 days, 35.3 months) was longer than those with PPC (708 days, 23.6 months) the difference was not statistically significant. However, Cox-2 expression was correlated with microvessel density in PPC (p=0.026) and OSC cases (p=0.005), and high expression of Cox-2 correlated with lower survival rate in OSC cases (p=0.045) but not in PPC cases (p=0.12). These findings, coupled with the morphologic overlap existing between OSC and PPC, support the view that they represent related pathologic entities.
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PMID:Expression of Cox-2, CD34, Bcl-2, and p53 and survival in patients with primary peritoneal serous carcinoma and primary ovarian serous carcinoma. 1508 45

In rats, esophagogastroduodenal anastomosis (EGDA) without concomitant chemical carcinogen treatment can lead to columnar-lined esophagus (CLE) including metaplasia, dysplasia, and esophageal adenocarcinoma (EAC). This study describes the morphology and phenotypic features of CLE and EAC in the rat model and compares them with the corresponding lesions in human Barrett's esophagus (BE). Swiss roll preparations of esophagi of EGDA rats and biopsies from human BE containing specialized intestinal metaplasia (SIM) and EAC were examined. The esophagi of EGDA rats showed esophagitis, CLE, islands of multilayered epithelium (MLE), dysplasia and EAC. The CLE had features of specialized intestinal metaplasia. MLE frequently occurred at the neo-squamocolumnar junction and occasionally in the mid-esophagus in isolated foci. Scattered mucinous cells in esophageal squamous epithelium were also found. The CLE and MLE in EGDA rats resembled the lesions described in human BE in morphology, mucin features and expression of differentiation markers (CK7, CK20, Das-1, villin, and pS2/TFF1). Invasive EAC in EGDA rat is of well-differentiated mucinous type, which is in contrast to the variably differentiated glandular type of adenocarcinoma in human BE. p53, c-myc, and cyclooxygenase 2 are expressed in both the rat and human SIM and EAC. These studies indicate that, not withstanding small differences, SIM and EAC induced in EGDA rats are similar to the corresponding lesions in human BE. EGDA rats may serve as a useful model to study the pathogenesis, molecular biology, and chemopreventive interventions of human BE and EAC.
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PMID:Phenotype of columnar-lined esophagus in rats with esophagogastroduodenal anastomosis: similarity to human Barrett's esophagus. 1509 11

Cyclooxygenase (Cox)-2 plays an important role in cell proliferation, carcinogenesis and tumor growth, in part through the synthesis of prostaglandin E2 (PGE2) as well as through other yet unknown routes. Epidermal growth factor receptor (EGFR) signaling regulates Cox-2 expression, which has not been thoroughly examined in bronchial carcinomas. The current study examined the expression of Cox-2, EGFR, P53 and proliferative marker Ki-67 immunoreactivities by immunohistochemistry in 71 surgically removed stage I bronchial adenocarcinomas. Furthermore, we evaluated the prognostic value of these molecules to elucidate the biological significance of Cox-2 expression. Higher Cox-2 expression (more than 10% immunoreactivities in tumor cells) was strongly associated with higher EGFR and P53 expression as well as a Ki-67 LI above 20% (P < 0.01). Cox-2 and EGFR immunoreactive tumor cells showed a similar distribution pattern. Five-year survival rate was 73% in 57 cases showing higher Cox-2 expression and 100% in 14 cases showing lower expression, indicating a significant difference in survival (P = 0.040). Higher Cox-2 expression might be associated with tumor progression and worse prognosis through EGFR signaling interaction in Stage I bronchial adenocarcinomas.
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PMID:Co-expression of Cox-2 and EGFR in stage I human bronchial adenocarcinomas. 1524 87

The duodenum is the second most frequent site of cancer in patients with familial adenomatous polyposis (FAP). The main objective of this study was to evaluate the cell kinetics in duodenal and ampullary adenomas in FAP. The endoscopic and biopsy findings of duodenal adenomas in 22 FAP subjects and 18 non-FAP subjects were compared. Adenomas in FAP included 15 ampullary adenomas and 17 nonampullary adenomas. The cell kinetics was evaluated by immunohistochemistry for Ki-67, p53, bcl-2, and cyclooxygenase 2 (COX2), and the apoptotic index (AI) as determined by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL) method. Any correlations between the indices for cell kinetics and the endoscopic findings were identified. All 50 adenomas were histologically verified to be tubular adenoma with low-grade dysplasia. Neither the expression of Ki-67, p53, bcl-2, and COX2 nor the AI differed substantially between FAP and non-FAP subjects. In patients with FAP, duodenal adenoma tended to have a higher Ki-67-labeling index than the ampullary adenoma (54.3 +/- 11.3 versus 46.8 +/- 12.7; .05 < P < .1). In addition, the Ki-67-labeling index in endoscopically normal or slightly enlarged ampullary adenoma was significantly higher than that in markedly enlarged ampullary adenoma (51.8 +/- 11.4 versus 39.4 +/- 11.3; P < .05). Duodenal adenoma in FAP subjects was not found to have a higher proliferative activity or a smaller degree of apoptosis compared with those in non-FAP subjects. The smaller proliferative activity in larger ampullary adenoma may thus be related to the static nature of ampullary adenoma in FAP.
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PMID:Immunohistochemical characteristics of duodenal adenomas in familial adenomatous polyposis with special reference to cell kinetics. 1571 84

To investigate whether protein expression of cyclooxygenase 2 (COX2) is associated with tumor phenotype, immunohistochemical alterations, and clinical outcome in urinary bladder cancer (BC). Tissue microarrays (n = 776) were used to analyze COX2, P53 and the Ki-67 labeling index immunohistochemically. A monoclonal mouse antibody was used after heat-induced antigen retrieval. COX2 expression was scored semiquantitatively (0-3+). COX2 expression was detected in 60% (368/617) of urothelial BC. Positive COX2 staining was seen in 77.8% (140/182) of muscle invasive urothelial BC, compared to 35% (7/20) of muscle invasive squamous cell carcinomas (p < 0.001). COX2 protein expression was associated with advanced tumor stage (p < 0.0001), high-grade histology (p < 0.0001), solid growth pattern in invasive BC (pT1-4, p = 0.02), high Ki-67 labeling index (p < 0.0001), and positive P53 IHC (p < 0.001). COX2 expression was not associated with survival, recurrence, and progression in clinically relevant subgroups (pTa, pT1, pT2-4). Expression of COX2 is common in advanced BC with poor prognostic characteristics, supporting efforts to initiate clinical trials on the efficacy of COX2 inhibitors in the adjuvant treatment of high-risk urinary BC.
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PMID:High-throughput tissue microarray analysis of COX2 expression in urinary bladder cancer. 1601 Apr 19

There is a lot of interest in the health benefits of dietary carotenoids and on the relationship of these compounds with smoke. In particular, it is unknown if the enhanced cancer risk observed in smokers following beta-carotene supplementation can be also found using other carotenoids. Here, we studied the effects of the tomato carotenoid lycopene on molecular pathways involved in cell cycle progression, apoptosis and survival in immortalized RAT-1 fibroblasts exposed to cigarette smoke condensate (TAR). Lycopene (0.5-2.0 microM) inhibited cell growth in a dose-and time-dependent manner, by arresting cell cycle progression and by promoting apoptosis in cells exposed to TAR. The arrest of cell cycle was independent of p53 and of 8-OH-dG DNA damage and related to a decreased expression of cyclin D1. Moreover, the carotenoid up-regulated apoptosis and down-regulated the phosphorylation of AKT and Bad in cells exposed to TAR. Such an effect was associated to an inhibition of TAR-induced expression of Cox-2 and hsp90, which is known to maintain AKT activity. This study suggests that lycopene, differently from beta-carotene, can exert protective effects against cigarette smoke condensate.
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PMID:Lycopene induces apoptosis in immortalized fibroblasts exposed to tobacco smoke condensate through arresting cell cycle and down-regulating cyclin D1, pAKT and pBad. 1621 89

Head and neck squamous cell carcinoma (HNSCC) involves the upper aerodigestive tract and can destroy the structure and function of organs involved in voice, speech, taste, smell and hearing, as well as vital structures necessary for survival. HNSCC has long been a treatment challenge because of the high rate of recurrences and of advanced disease at the time of diagnosis. Molecular identification of tissue biomarkers in diagnostic biopsy specimens may not only identify patients at risk for developing HNSCC but may also select patients that may benefit from more aggressive treatment modalities. Several biomarkers studied to date such as the proteins p53, cyclin D1, p16, Cox-2 enzyme, epidermal growth factor and vascular endothelial growth factor receptors, matrix metalloproteinases and the Fhit marker for genomic instability could be manipulated for the therapeutic benefit of these patients. This review presents the most updated information on molecular biomarkers with the greatest prognostic potential in HNSCC and discusses some factors that contribute to the controversy concerning their prognostic importance.
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PMID:Molecular predictors of clinical outcome in patients with head and neck squamous cell carcinoma. 1630 41

Cyclooxygenases-1 and -2 (Cox-1 and Cox-2) are two distinct isoforms that catalyze the conversion of arachidonic acid to prostaglandins. The role of Cox-2 in a variety of cancers is well recognized, but the contribution of Cox-1 remains much less explored. We have previously shown that human epithelial ovarian tumors have increased levels of Cox-1, but not Cox-2. We also observed that Cox-1 is highly expressed in a mouse model of epithelial ovarian cancer (EOC), which lacks p53 but overexpresses c-myc and K-ras or c-myc and Akt. More importantly, a Cox-1-selective inhibitor, SC-560, attenuates EOC growth. In the present investigation, we used various genetically engineered mouse models of EOC to determine whether Cox-1 overexpression is unique to specific genetic and oncogenic alterations or is widespread. These models include: (a) deletion of both p53 and Rb, (b) induction of the transforming region of SV40 under the control of Mullerian inhibitory substance type II receptor, or (c) activation of K-Ras in the absence of Pten locally in the ovarian surface epithelium. We found that these three models, which produce spontaneous EOC, also show up-regulated expression of Cox-1, but not Cox-2. The results provide further evidence that Cox-1 overexpression is common in various models of EOC. Thus, Cox-1 serves as a potential marker of EOC and is a possible target for the prevention and/or treatment of this deadly disease.
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PMID:Cyclooxygenase-1 is overexpressed in multiple genetically engineered mouse models of epithelial ovarian cancer. 1651 May 68

Malignant gastrointestinal tumors are still worldwide a very common cause of death from cancer. Even though the surgical techniques and the neoadjuvant/adjuvant therapies have improved over the last years and multimodal concepts in cancer treatment have been established, these types of tumors remain a challenge. Therefore predictive/prognostic markers need to be established, to be able to tailor chemotherapies and therefore improve efficacy of neoadjuvant/adjuvant treatment. Over the last years potential predictive/prognostic factors have been characterized by molecular-biological technologies: the tumor suppressor gene p53, the cell-cycle regulatory proteins p21 and p27, the marker of proliferation Ki-67, the epidermal growth factor receptor, HER2/neu, angiogenetic factors (the vascular endothelial growth factor, cyclooxygenase 2, thymidine phosphorylase), enzymes involved in the DNA-repair-system (ERCC1), enzymes involved in the 5-fluorouracil-metabolism (thymidylate synthase, dihydropyrimidine dehydrogenase) or other genetic alterations, like the loss of heterozygosity or the microsatellite instability. The results of the mainly retrospective studies are promising but prospective studies are needed to validate those markers in the therapy of gastrointestinal tumors. The goal is that we will be able to predict when and with what to treat.
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PMID:[Predictive and prognostic factors in the neoadjuvant/adjuvant therapy of gastrointestinal tumors: wishful thinking or reality?]. 1661 82

Breast cancer is a heterogeneous disease that encompasses a wide range of histopathological types including: invasive ductal carcinoma, lobular carcinoma, medullary carcinoma, mucinous carcinoma, tubular carcinoma, and apocrine carcinoma among others. Pure apocrine carcinomas represent about 0.5% of all invasive breast cancers according to the Danish Breast Cancer Cooperative Group Registry, and despite the fact that they are morphologically distinct from other breast lesions, there are at present no standard molecular criteria available for their diagnosis. In addition, the relationship between benign apocrine changes and breast carcinoma is unclear and has been a matter of discussion for many years. Recent proteome expression profiling studies of breast apocrine macrocysts, normal breast tissue, and breast tumours have identified specific apocrine biomarkers [15-hydroxyprostaglandin dehydrogenase (15-PGDH) and hydroxymethylglutaryl coenzyme A reductase (HMG-CoA reductase)] present in early and advanced apocrine lesions. These biomarkers in combination with proteins found to be characteristically upregulated in pure apocrine carcinomas (psoriasin, S100A9, and p53) provide a protein expression signature distinctive for benign apocrine metaplasias and apocrine cystic lesions. These studies have also presented compelling evidence for a direct link, through the expression of the prostaglandin degrading enzyme 15-PGDH, between early apocrine lesions and pure apocrine carcinomas. Moreover, specific antibodies against the components of the expression signature have identified precursor lesions in the linear histological progression to apocrine carcinoma. Finally, the identification of proteins that characterize the early stages of mammary apocrine differentiation such as 15-PGDH, HMG-CoA reductase, and cyclooxygenase 2 (COX-2) has opened a window of opportunity for pharmacological intervention, not only in a therapeutic manner but also in a chemopreventive setting. Here we review published and recent results in the context of the current state of research on breast apocrine cancer.
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PMID:Molecular pathology of breast apocrine carcinomas: a protein expression signature specific for benign apocrine metaplasia. 1663 54


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