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 clinicopathologic features, including a detailed immunohistochemical, ultrastructural, and flow cytometric analysis, are described in three cases of atypical carcinoid tumor of the larynx. All patients had metastatic disease within cervical lymph nodes at presentation and eventually developed distant metastases. Special stains revealed focal intracytoplasmic mucin accumulation, and immunohistochemistry showed the tumors to be positive for CAM 5.2, CEA, chromogranin A, and calcitonin. In two cases, double-staining techniques revealed occasional cells that stained for both mucin and chromogranin A. The histochemical and immunohistochemical findings in these two cases were confirmed at the ultrastructural level, with most tumor cells containing many neurosecretory granules. Smaller numbers of cells contained mucin vacuoles and, in occasional cells, both mucin and neuroendocrine granules were identified. The three tumors exhibited positive staining with D07 (anti-p53), and flow cytometric analysis revealed DNA aneuploidy and polyploidy. The double-staining and ultrastructural features indicate that laryngeal atypical carcinoid qualifies for the designation of true amphicrine carcinoma. Further study is necessary to determine whether mutation of the p53 gene is important in the evolution of laryngeal neuroendocrine tumors and whether DNA aneuploidy or polyploidy identifies a subset of these tumors with a poor prognosis.
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PMID:Atypical carcinoid tumor of the larynx: an immunohistochemical, ultrastructural, and flow cytometric analysis. 927 73

Pancreatic adenocarcinoma is one of the most incurable and least understood of all human cancers. It is the fourth leading cause of cancer-related mortality in males (after lung, prostate, and colon) and in females (after lung, breast, and colon) in the United States with <2-3% of patients surviving >5 years. In an attempt to search for more effective therapies for this disease, we report here, for the first time, an effective treatment, the combination of gemcitabine and auristatin-phenethylamine (PE), against an orthotopic implantation of a human pancreatic adenocarcinoma cell line (HPAC) in severe combined immunodeficient (SCID) mice. Tumor implantation was performed by injecting 100 microl of the HPAC cell suspension (1 x 10(6) cells) directly into the pancreas of 5-week-old SCID mice. After implantation, tumor formation was checked twice a week. All palpable tumors were detected within 21 days (100% take rate), and tumors were confirmed histologically to be pancreatic adenocarcinoma. For the subsequent efficacy trial, tumor-bearing SCID mice were randomized into four groups with five mice in each group. One served as a control, the second received gemcitabine alone (2.5 mg/kg/injection i.p.), the third received auristatin-PE alone (2.0 mg/kg/injection i.v.), and the fourth group received the combination of gemcitabine (i.p.) and auristatin-PE (1.5 mg/kg/injection i.v.). All animals were euthanized 7 days after the completion of their treatments, and the pancreases were resected. Histological examination revealed the tumors to be adenocarcinoma. The tumors were composed of diffuse sheets of cells interrupted by glandular spaces containing secretory material. Cytologically, the tumor cells were large, pleomorphic, and hyperchromatic. Many cells contained intracellular lumina containing mucin. Immunohistochemical studies showed strong p21WAF1 (p21) expression but no immunoreactivity with p53 and Her-2/neu antibodies. The mean pancreatic weight in the gemcitabine/auristatin-PE combination group was significantly (P = 0.014) lower (0.84 +/- 0.639 g) when compared with those of the control (2.91 +/- 1.19 g) and gemcitabine alone (1.84 +/- 0.796 g; P = 0.064) groups. In addition, the mean weight in the combination group approached statistical significance when compared with the auristatin-PE group alone (1.16 +/- 0.635 g; P = 0.028). We conclude that the combination of gemcitabine and auristatin-PE is an effective treatment against HPAC tumors in this xenograft model and more effective than treatment with either gemcitabine or auristatin-PE alone and could be considered for future animal studies with pancreas cancer and/or for human clinical trials.
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PMID:An orthotopic model of human pancreatic cancer in severe combined immunodeficient mice: potential application for preclinical studies. 956 82

Human acinic cell adenocarcinoma cell (HACC) line was established from the pleural effusion that contains metastatic tumor cells of acinic cell adenocarcinoma of papillary and microcystic type originating from the parotid gland. The HACC cells grew in an adherent monolayer with a doubling time of 66 h. Implanted tumor of SCID mice revealed similar histological findings to that of the primary tumor. The HACC cells produced mucin and expressed epithelial markers as well as alpha1-antitrypsin and lysozyme, whereas salivary peptide P-C was expressed in cultured HACC cells but not in the primary and implanted HACC cell tumors. S-100 protein was also expressed in both the primary tumor and HACC cell line. Neither amplification of common oncogenes nor expression of p53 was observed. The receptor for epidermal growth factor (EGF) was expressed, indicating EGF and transforming growth factor-alpha (TGF-alpha) enhanced the growth of the HACC line. Unexpectedly, tumor necrosis factor-a (TNF-alpha) also enhanced the growth of the HACC line significantly. However, there was no evidence of autocrine growth using these growth factors. In contrast, TGF-beta1 inhibited the growth of the HACC cell line through apoptosis. The HACC cell line has features similar to both acinar and intercalated ductal cells of the salivary gland. Epidermal growth factor, TGF-alpha and TNF-alpha are potential growth factors for the HACC cell line. The HACC cell line may be a good model for studying the biological behavior of salivary gland neoplasms.
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PMID:Characterization of a newly established human acinic cell adenocarcinoma cell line (HACC) originating from the salivary gland: morphological features and role of various growth factors on the growth of the HACC cell line. 978 63

Two examples of a rare but distinctive morphologic variant of extremely well-differentiated adenocarcinoma of the extrahepatic bile ducts are reported. One tumor arose in the common bile duct of a 51-year-old man; the other arose in the common hepatic duct of a 27-year-old man. Both tumors were composed predominantly (>95%) of gastric foveolar-type epithelium. Because of their bland nuclear features, low mitotic index, and focal polypoid and lobular architecture, they were initially confused with adenomas. Foci of less-differentiated adenocarcinoma and perineural invasion present in the deep portions of the tumors facilitated recognition. The neoplastic cells and extracellular mucin were periodic acid-Schiff- and alcian blue-positive. By immunohistochemistry, the tumor cells expressed cytokeratins 8 and 20 as well as cathepsin D, as reported in normal foveolar cells. Likewise, p53 overexpression was documented immunohistochemically in both adenocarcinomas, which also stained with the Ki-67 antibody. Despite the well-differentiated nature of the neoplasms and their deceptively benign microscopic appearance, one patient developed recurrence and liver metastasis 5 years after surgery. The other patient is disease-free 2 years following a segmental resection of the common hepatic duct, cystic duct, and gallbladder. The cell phenotype of these tumors can be explained by the ability of the bile duct epithelium to differentiate along gastric cell lines.
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PMID:Well-differentiated adenocarcinoma, gastric foveolar type, of the extrahepatic bile ducts: A previously unrecognized and distinctive morphologic variant of bile duct carcinoma. 1019 86

The clinicopathological features of 56 patients with mucinous cystic tumors (MCTs) of the pancreas were studied. Particular attention was paid to the prognosis of MCTs and the relationship to their ovarian, hepatic, and retroperitoneal counterparts. To distinguish MCTs from pancreatic intraductal papillary-mucinous tumors, MCTs were defined as tumors lacking communication with the duct system and containing mucin-producing epithelium, usually supported by ovarian-like stroma. All 56 tumors occurred in women (mean age 48.2 years) and were preferentially (93%) located in the body and tail of the pancreas. In accordance with the WHO classification, MCTs were divided into adenomas (n = 22), borderline tumors (n= 12), and noninvasive and invasive carcinomas (n = 22). Survival analysis revealed the extent of invasion to be the most significant prognostic factor (p<0.0001). Malignancy correlated with multilocularity and presence of papillary projections or mural nodules, loss of ovarian-like stroma, and p53 immunoreactivity. Stromal luteinization with expression of tyrosine hydroxylase, calretinin, or alpha inhibin was found in 66% of the cases. We conclude that the biologic behavior of MCTs is predictable on the basis of the extent of invasion. The similarities (i.e. gender, morphology, stromal luteinization) between pancreatic MCT and its ovarian, hepatobiliary, and retroperitoneal counterparts suggest a common pathway for their development.
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PMID:Mucinous cystic tumors of the pancreas: clinicopathological features, prognosis, and relationship to other mucinous cystic tumors. 1019 70

We studied the background gastric mucosa in eight patients with intractable peptic ulcer in whom gastric cancer developed during more than 4 years' administration of histamine (H)2-receptor antagonists (H2-RAs), and in two patients with intractable gastric ulcer without gastric cancer in whom H2-RAs were administered for 4 years. As controls, we studied background mucosa in seven patients with combined gastroduoderal ulcers not treated with H2-RAs. The cancers were differentiated adenocarcinomas in all eight patients. The characteristic features of these patients and of the two patients with intractable gastric ulcer were: expansion of the generative cell zone, poor differentiation of the goblet cells, mild cellular atypia, and abnormal branching and anastomosis of glands, as well as wide areas of incomplete-type intestinal metaplasia. The sites of the differentiated adenocarcinomas were classified by mucin histochemistry as intestinal-type mucosa in all patients. A special type of incomplete intestinal metaplasia, of the intestinal type and which retained gastric-type properties, was present in some areas, and p53-positive cells were observed in some areas. In patients with intractable gastric ulcer in whom the background gastric mucosa had been exposed to more than 4 years of H2-RA treatment, it was considered possible that the preconditions for cancerous lesions were present.
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PMID:Clinicopathological study of background gastric mucosa during long-term conservative maintenance therapy for intractable peptic ulcer. 1020 6

Adenocarcinomas of the breast behave clinically and epidemiologically in ways that show host resistance factors are important for outcome in addition to grade and stage of malignancy. Immune reactivity to autologous tumors is indicated by the general presence of lymphoid infiltration (LI) and regional lymph node changes; however, these changes predict favorable outcome only in non-metastatic disease. LI is characterized by CD4+ and CD8+ tumor infiltrating lymphocytes reflecting latent cell-mediated immunity (CMI). CMI and humoral immune reactivity have been demonstrated to autologous tumor and a variety of tumor-associated antigens (TAA) have been implicated including CEA, HER-2/neu, MAGE-1, p53, T/Tn and MUC-1. Immune incompetence involving CMI is progressive with the stage of breast cancer and is prognostically significant. Immunotherapy of several types has been designed to address this immunodeficiency and the TAAs involved. Animal models have employed drug therapy, cytokine transfection, vaccines with autologous tumor, cytokines like interferon alpha (IFN-alpha) and interleukin-2 (IL-2), TAA tumor vaccines, and immunotoxins with evidence of tumor regression by immunologic means. Immunotherapy of human breast cancer is a rapidly growing experimental area. Positive results have been obtained with natural IFN and interleukins, particularly in combination strategies (but not with high dose recombinant IFN or IL-2), with autologous tumor vaccine (but not yet with transfected autologous tumor); with a mucin carbohydrate vaccine (Theratope) in a combination strategy (but not with mucin core antigen) and with several immunotoxins. Combination strategies involving immunorestoration, contrasuppression, adjuvant, and immunotoxins are suggested for the future.
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PMID:The immunology and immunotherapy of breast cancer: an update. 1023 Aug 72

Because of the difficulty in obtaining biopsy specimens from pancreatic cancer patients, K-ras mutation analysis in pancreatic juice has been used for specific diagnosis. But recently, false positives have been obtained with this method. To improve the genetic diagnosis of pancreatic cancer, detection of p53 gene mutation in pancreatic juice was studied. Pancreatic juice was sampled endoscopically. Single-strand conformation polymorphism analysis was used for p53 mutation analysis. Furthermore, K-ras mutations at codon 12 were also studied in the same pancreatic cancer patients. Of 26 cases of pancreatic cancer, p53 mutations were detected in 11 (42.3%). No mutations were seen in the cases with mucin-producing adenoma nor with chronic pancreatitis. K-ras mutations were detected in 84.0% of cases by RFLP analysis, which has high sensitivity, and in 65.3% by hybridization protection assay, which has high specificity. Using a combination assay with both genes, genetic abnormalities were detected in 92.0% by RFLP and 73.1% by hybridization protection assay including two cases in which p53 alone was positive by both methods. The specificity of p53 mutation for pancreatic cancer is very high. Therefore, simultaneous analysis of p53 and K-ras mutation is suggested to enhance the genetic diagnosis of pancreatic cancer.
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PMID:Detection of mutations of p53 tumor suppressor gene in pancreatic juice and its application to diagnosis of patients with pancreatic cancer: comparison with K-ras mutation. 1035 50

Fifty sporadic colorectal carcinomas diagnosed in 1991 were analysed for microsatellite instability at four loci. Five of 50 (10 per cent) tumours showed replication errors (RERs) at two or more loci and were classed as RER-positive (RER+). A further five showed RERs at one locus only. A significant association (Fisher exact test) was found between RER+ tumours and location in the proximal colon, exophytic shape, size >5 cm, histological margin, lymphoid reaction, and near-diploid DNA content. There was no significant difference for age, sex, grade, mucin production, p53 protein overexpression or Duke's stage. There was no significant difference in survival as measured over a 60-month follow-up period. The findings, though limited by the small case numbers involved, show an association between RER positivity in sporadic colorectal tumours and certain clinico-pathological features. They do not suggest a better clinical outcome for sporadic RER+ tumours.
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PMID:Microsatellite instability in sporadic colorectal carcinoma is not an indicator of prognosis. 1039 34

Villous tumors are rare and their histological diagnosis from biopsy specimens is often difficult. To ascertain its tumor progression, including the genetic events, would be useful for clinical treatment. Clinicopathological features and the expression of p53 and bcl-2 proteins were investigated in 50 villous tumors from 49 patients. The patients' ages ranged widely from 32 to 84 years (average, 61 years). Females were more frequently affected than males (male:female ratio, 20:29). Thirty-six (72%) of the villous tumors were present within the sigmoid colon and rectum. Histologically, 17 (34%) of these contained carcinomas in villous adenomas (CIVA), while 24 (73%) of 33 villous adenomas (VA) contained high-grade dysplasia. Most of the CIVA revealed well-differentiated adenocarcinoma, often with focal or diffuse mucin pools. Three lesions of invasive carcinomas were composed of extremely well-differentiated components. The average size of the CIVA (79 mm) was significantly larger than that of the VA (51 mm). Overexpression of p53 protein was recognized in 12% of VA, in 24% of mucosal components of CIVA and in 18% of invasive components of CIVA. Overexpression of bcl-2 was recognized in 57% of VA, 33% of mucosal components of CIVA, and 7% of invasive components of CIVA. Several characteristic features were recognized in villous tumors, which comprised: (i) a high frequency of coexistence of carcinoma; (ii) multiple foci of carcinomas arising in adenomatous tumors; (iii) a lower histological grade of carcinomas, often with mucin pools; (iv) the existence of extremely well-differentiated adenocarcinomas; and (v) less frequent expression of p53 protein in the carcinomatous components. According to these findings, the pathway of tumor progression in the villous tumors is possibly different from that of sporadic colorectal carcinomas. Because of the peculiarity of villous tumors, careful clinical management is required.
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PMID:Villous tumor of the colon and rectum with special reference to roles of p53 and bcl-2 in adenoma-carcinoma sequence. 1041 79


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