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)

Esophageal cancer is an important problem in the United States. It results in more deaths (over 10,000 annually) than rectal cancer. Furthermore, the incidence of esophageal adenocarcinoma is increasing at a rate faster than that of nearly any other cancer and the reasons for the increase are not well understood. A variety of tumor-suppressor genes (including p53, APC, DCC and Rb) and proto-oncogenes (including prad1, EGFR, c-erb-2 and TGF alpha) may be involved in the development and progression of esophageal cancer. Clinical prognostic factors include stage, Karnofsky performance status, sex, age, anatomic location of the tumor, and degree of weight loss. A new staging system based on depth of wall penetration and lymph node involvement correlates well with prognosis for patients undergoing esophagectomy. Newer staging procedures including endoscopic ultrasound as well as the use of minimally invasive surgery, such as thoracoscopy and laparoscopy, may allow accurate staging without esophagectomy. Surgical resection provides excellent palliation; however, the chance for cure with esophagectomy alone is only 10% to 20%. Adjuvant treatment with pre- or postesophagectomy radiation may improve local-regional control but does not improve survival. Nor has preoperative chemotherapy been shown to improve survival; however, it remains an active area of investigation. Multimodality therapy, namely, chemotherapy and radiation (chemoradiation), given concurrently prior to surgical resection shows promise, with one study indicating a 5-year survival of 34%. A complete pathologic response to chemoradiation correlates with improved survival. Chemoradiation has been shown to be superior to radiation as primary management of esophageal cancer. There has been no successfully completed randomized trial of surgery versus definitive radiation or chemoradiation. However, chemoradiation represents a reasonable alternative to esophagectomy in the primary management of squamous cell carcinoma of the esophagus and chemoradiation also appears to be effective in the treatment of patients with adenocarcinoma of the esophagus, offering significant palliation and a chance for long-term survival as well. Randomized studies of preoperative chemoradiation versus surgery or versus chemoradiation alone are needed. The treatment of advanced esophageal cancer must be directed toward palliation of symptoms. Newer endoscopic techniques, including the use of expansile metal stents, laser ablation, intraluminal high-dose rate brachytherapy, BICAP tumor probe, or photodynamic therapy, offer selected patients short-term palliation.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Esophageal cancer. 753 69

A case with primary triple cancers including thyroid cancer is reported. A 57-year old woman complaining of laryngeal discomfort was found to have an firm elastic lump on the right anterior neck. On 123I scan, the nodule in the right thyroid lobe accumulated considerable amounts of radioiodine as a warm nodule, while the remainder of the gland showed decreased uptake. Thyroid hormone levels remained within normal ranges. Cytological findings obtained by fine-needle aspiration biopsy showed papillary carcinoma. Right lobectomy was performed. The histological examinations revealed papillary carcinoma embedded within adenomatous thyroid tissue. It is probable that the surrounding adenomatous tissue accumulated radioiodine, since the warm nodule on 123I scan was larger than the size of the carcinoma. Examinations of the gastrointestinal tract revealed the presence of poorly differentiated adenocarcinoma in the stomach and well differentiated adenocarcinoma (carcinoma in adenoma) in the rectum. Expressions of ras p21 and p53 were examined immunohistochemically in these carcinoma tissues. The ras p21 product was clearly detected in not only the thyroid carcinoma but in a part of the surrounding adenomatous regions as well. Both ras p21 and p53 proteins were observed in the rectal cancer tissue. In contrast, these oncoproteins were not found in the gastric cancer tissue. In this case ras oncogene activation may be an early event in the tumorigenic process of the thyroid and rectum. However, different genetic alterations seem to occur during the development of these three carcinomas.
 ...
PMID:[A case report of primary triple cancers in the thyroid, stomach and rectum with evidence of variable oncoprotein expressions]. 800 92

For a better quality of life in rectal cancer patients, high dose radiotherapy following abdominoperineal resection of the rectum with a pelvic partition is another surgical option replacing extended abdominoperineal resection. In addition to pelvic partition with polyglycolic acid mesh, the tissue expander was inserted into the pelvic cavity to support the intestine upward and the bladder forward. The mean total radiation dosage was 5040 cGy. Between 1989 and 1991, 10 patients were treated according to this method. Out of 10 patients 9 were free of recurrence, and only one had hepatic metastasis. In addition, postoperatively, the average residual urine by this method was 39.1 ml and was statistically different compared to a figure of 200 ml in conventional abdominoperineal resections (p < 0.001, "t"-test). In order to individualize the operative procedures among a variety of surgical options, the molecular biological technique was utilized. In p53 stain analysis of 114 colorectal cancer patients, patients with p53 positive staining reached a higher stage than those with p53 negative staining (p < 0.05, chi 2 analysis). Therefore, we surmised that the positivity of the p53 stain could be one of the factors gauged as an indication of postoperative high-dose radiation. In conclusion, high-dose postoperative radiotherapy was thought to be one of the treatment modalities to improve the survival and quality of life of advanced rectal cancer in selected cases.
 ...
PMID:Extended lymphadenectomy and the quality of life in rectal cancer patients. 806 50

From a histologic and endoscopic standpoint, colon and rectal cancer (CRC) begins as a small neoplastic polyp which progressively enlarges and transforms through a dysplasia stage into invasive cancer. Recently, molecular abnormalities underlying the adenomacarcinoma progression have been defined. The adenomatous polyposis coli (APC) gene and mismatch repair genes are found to be dysfunctional early in the neoplastic process; either as inherited or somatic mutations. Subsequently, polyps progress to cancer along one of two paths depending on which gene is abnormal. When the APC gene is the initial mutation tumor development follows the "loss of heterozygocity" (LOH) pathway. If mismatch repair genes are altered, the "replication error" (RER) pathway is followed. Somatic mutations of the K-ras oncogene and the MCC, DCC, and p53 tumor suppressor genes accumulate in the LOH pathway and mark the progression through polyp stages. Microsatellite instability is a characteristic of the RER pathway but the precise genes involved in this pathway currently are not known. Defining these pathways has led to a new classification scheme for CRC with resultant changes in our clinical approach to screening, surveillance, and treatment.
 ...
PMID:Molecular biology of colon polyps and colon cancer. 860 8

This study investigated the predictive value of p53 nuclear overexpression on recurrence of colorectal adenocarcinomas compared with established prognostic pathological features. Sixty-one paraffin-embedded sections from primary tumours were examined by immunohistochemistry. Specific nuclear staining was detected in 27 (44.2%) cases. Positivity was more frequent in tumours with venous invasion (76.9%) (P = 0.06) and in rectal cancer (68.4%) (P = 0.06). After a median observation time of 46 months, p53-positive tumours exhibited a higher percentage of recurrence (40.7% vs 11.7%) (P = 0.03), and a higher likelihood of relapse at 5-year follow-up (46% vs 13%) (P = 0.006). Among the pathological variables analysed, only the extent of bowel wall invasion showed a relationship with recurrence. After adjustment for the other covariates in a Cox's regression model, p53 overexpression was the only factor showing independent prognostic significance (hazard ratio: 4.96; 95% Confidence Interval (CI): 1.47-16.71) (P = 0.012). The results of this study show that nuclear p53 protein overexpression has higher predictive value than standard pathological variables.
 ...
PMID:Prediction of recurrence in B-C stages of colorectal cancer by p53 nuclear overexpression in comparison with standard pathological features. 863 11

Overexpression of p53 protein was studied in neoplastic specimens of 150 patients registered for colorectal adenocarcinoma in the Health Care District 16 of Modena, Italy, from 1984 to 1986. We selected Dukes' stage B (92) and C (58) patients whose survival and recurrence rates are not easily predictable, with the purpose of defining subgroups of patients at high risk of recurrence. Monoclonal antibody PAb 1801 was used on formalin-fixed, paraffin embedded specimens. Nuclear staining was assessed to divide tumours into three groups: a) negative, b) low expressors, c) high expressors. Histomorphological variables of tumours, major clinical features of the patients and 5-year specific survival, were evaluated and related to p53 status. p53 was found in 71 out of 150 cases (47.3%); 50 tumours were high and 21 low expressors. No correlation was found between p53 overexpression and clinico-pathological variables. No difference in survival was found between patients with p53 positive and negative tumours in the entire series or within Dukes' stage B and C patients. However, the subgroup of patients with stage C rectal cancer seemed to have a better prognosis if the tumour was p53 negative (of borderline significance, p = 0.15). The same results were obtained by grouping low expressor tumours alternatively with negative or high expressors. We conclude that p53 nuclear overexpression does not seem to influence the prognosis of Dukes' stage B or C colorectal cancer patients.
 ...
PMID:Clinico-pathological correlation and prognostic significance of nuclear p53 protein in colorectal cancer. Colorectal Cancer Study Group of the University and Health Care District of Modena. 884 35

Evolving trends in the management of rectal cancer have focused on organ preservation, improved quality of life, and survival of patients. A significant shift is underway in our thinking about what constitutes the true rectum and defining the "proximal" and "distal" segments of the rectum. Tumor mobility remains a dominant prognostic factor in patient selection and choice of surgery. A clinical staging with tumor location in the rectum provides a logical algorithm for treatment decision making with either chemoradiation therapy or surgery as initial treatment of choice. Current rectal cancer management has largely focused on postoperative adjuvant radiation strategies with improvement reported for T3 and N+ cases. Recent data from Europe suggests that preoperative radiation has a significant advantage over surgery alone or postoperative treatment. This appears to be borne out by institutional studies of high-dose preoperative radiation (>45 Gy) in the United States. Aggressive preoperative combined chemoradiation has also led to significant downstaging of cancer with pathological complete response rates of 20% to 30%. This offers new options for surgical management of residual disease with endocavitary radiation or local excision. The development of new agents Gemcitabine, paclitaxel, and CPT-11 may also prove beneficial. New treatment strategies need to be coordinated with evolving knowledge of the biological behavior of the tumor based on its genetic fingerprints. c-Ki-ras and C-myc mutations have been implicated in tumor initiation and progression. A number of other tumor suppressor genes, APC gene, p53, and DCC have also been implicated in colorectal tumor carcigenesis. The modification of biological behavior by mutations in these genes is currently under study. This may guide new treatment strategies significantly reducing the death rates from rectal cancer and improving functional results of treatment.
 ...
PMID:Critical issues in the evolving management of rectal cancer. 942 68

The tumour-suppressor gene p53 encodes a transcription factor that plays a critical role in the induction of G1 cell cycle arrest and apoptosis after DNA damage. To clarify the role of the p53 gene and apoptosis in combined hyperthermia, chemotherapy and radiation (hyperthermochemoradiotherapy, HCR therapy) for rectal cancer, we examined the histological response, rate of apoptosis, DNA fragmentation and p53 status in tumours from 28 patients undergoing HCR therapy before surgery and from 22 patients who did not have preoperative treatment. The therapeutic effect of HCR therapy was closely correlated with the rate of apoptosis; the correlation was statistically significant, suggesting that this effect occurs through apoptosis. The incidence of p53 mutations in the treated group were as follows: in tumours resistant to HCR therapy, four of seven (57.1%); intermediately sensitive, 7 of 13 (53.9%); or sensitive, three of eight (37.5%), suggesting that the therapeutic effect and apoptosis rate were related to the p53 status of the tumours to some extent, but the relation was not statistically significant. In the 22 control tumours (non-treated group), the apoptosis rate was 2.0 +/- 1.1%, and there was no significant difference in p53 status compared with the HCR group. Our study indicates that the pathological response to HCR therapy correlates with the rate of apoptosis with statistical significance and that it induces the therapeutic effect more significantly in rectal cancer cells with wild-type p53, although HCR therapy-induced apoptosis also occurs in some rectal cancers with mutated p53. Therefore, this combination therapy can induce an additive or synergistic anti-tumour effect in rectal cancers with wild-type p53 as well as in those with mutated p53 through apoptosis, offering new therapeutic opportunities and a better prognosis.
 ...
PMID:Analysis of histological therapeutic effect, apoptosis rate and p53 status after combined treatment with radiation, hyperthermia and 5-fluorouracil suppositories for advanced rectal cancers. 945 62

Defective DNA mismatch repair proteins fail to correct replication errors (RERs). These defects may lead to secondary, mutation of oncogenes and tumor suppressor genes. Microsatellite instability might be a marker of such replication errors. Eighteen rectal tumors were examined to evaluate genetic instability, in sporadic rectal cancer by PCR. RERs were observed in 27.8% of the cases. No significant difference was noticed between RER+ and RER- patients as far as prognosis, clinicopathological features and p53 gene mutation are concerned. The incidence of nm23 gene mutation was the only statistically significant difference between the 2 groups. Three patients with only one altered microsatellite showed advanced tumor and nm23 gene mutation. Two cases with 5 altered microsatellites and nm23 gene mutated are disease-free: in one of them the p53 gene was also mutated. Probably more than one altered microsatellite is necessary to protect from the effects of secondary mutations.
 ...
PMID:Genetic instability, p53 and nm23 mutation and clinicopathological features in rectal carcinoma. 961 52

The object of this study was to evaluate cellular markers which included tumor cell p53 expression, cell proliferation antigens and DNA ploidy in both primary and locally recurrent rectal cancer. The study included 16 locally recurrent rectal cancer and 24 non-recurrent primary rectal cancer. Levels of p53 and Ki-67 expression were quantified and the DNA ploidy analyzed. In the locally recurrent group, labelling index of p53 was significantly higher in the short disease-free interval (DFI) (<2 years) group than the long DFI (> or = 2 years) group (p<0.05). It was immunohistochemically proved that DNA aneuploidy was reflected by accumulation of mutated p53 in both primary rectal cancer and locally recurrent tumors. The early local recurrence after curative operation for rectal cancer was associated with the number of p53 positive cells.
 ...
PMID:Evaluation of p53, Ki-67 and DNA ploidy in both primary rectal carcinomas and locally recurrent tumors. 968 40


1 2 3 4 5 6 7 8 9 10 Next >>