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)

Eight histiocytic sarcomas, identified by examination of more than 2000 malignant lymphomas, are described. For comparison, tumor infiltrates from five monoblastic leukemias were also analyzed. The histiocytic sarcomas were all high-grade malignancies consisting of markedly pleomorphic large cells with many mitotic figures. At presentation, six of the patients had systemic symptoms (fever, fatigue, loss of weight), skin infiltrates, and lymphadenopathy. Despite aggressive chemotherapy, clinical remissions were short, and six patients died of disease .5-48 months (mean, 6.5 months) after diagnosis. The remaining two patients are alive and in partial or complete remission 7 and 12 months after diagnosis. Immunotypic examination showed that all the histiocytic sarcomas were positive for macrophage-related antigens and negative for antigens on B cells, T cells, myeloid cells, epithelial cells, and melanocytes. T-cell receptor and immunoglobulin genes were studied in three cases and were present in a germline configuration. One of the histiocytic sarcomas resembled Langerhans' cells in phenotype and morphology; it was classified as a Langerhans' cell sarcoma. The remaining histiocytic sarcomas did not express accessory cell-associated antigens, but more closely resembled "ordinary" tissue macrophages; they were positive for lysozyme and/or CD68, followed in frequency by CD11c, CD4, CD11b, CDw32, peanut agglutinin receptor, and CD13. Similar features were seen in the monoblastic leukemias. These conditions could only be distinguished from histiocytic sarcoma by clinical and morphologic, rather than immunophenotypic, criteria. Expression of oncoprotein p53 was studied in nine cases and was positive in six of six histiocytic sarcomas and one of three monoblastic leukemias. Rare malignancies show features consistent with the derivation from macrophages. Two entities may be distinguished: those that resemble antigen-presenting accessory cells and those that more closely resemble ordinary tissue macrophages. Recognition of these tumors is important clinically and requires assessment of clinical, morphologic, and immunophenotypic features, supplemented by analysis of T-cell receptor and immunoglobulin genes. Whether (or how) p53 gene mutations are implicated in their pathogenesis will be an important topic for future investigation.
 ...
PMID:Histiocytic sarcomas and monoblastic leukemias. A clinical, histologic, and immunophenotypical study. 803 67

Most renal cell carcinomas (RCC) are composed of clear cells with sinusoid-like vasculatures and originate from the proximal tubule. On the other hand, collecting duct carcinoma (CDC) and chromophobe RCC are thought to originate from the lower nephron. In the present study, we present a case of unusual RCC. The patient was a 68-year-old Japanese woman who had developed general fatigue with hematuria. Computed tomography revealed a left renal tumor suggesting sarcoma. The resected tumor was located in the renal parenchyma, measuring 12 x 10 x 8 cm in size. Histologically, the tumor consisted principally of cuboidal cells forming parallel or radiating arrays, continuous with the spindle-shaped cells. Most parts of the tumor showed hemorrhagic necrosis. Immunohistochemically, tumor cells were positive for high molecular weight cytokeratins, vinculin, vimentin, CD15 and epithelial membrane antigen, and showed affinities with some kinds of lectins. N- and E-cadherins and beta-catenin were diffusely positive in tumor cells. Nuclear positivity for Ki-67 and p53 protein were approximately 2.0 and 1.7%, respectively. Considering its morphological and histochemical natures, this tumor is considered to have originated from the lower nephron, which is unique for a tumor of low-grade malignancy.
 ...
PMID:Low-grade renal cell carcinoma arising from the lower nephron: a case report with immunohistochemical, histochemical and ultrastructural studies. 1184 69

BBR3464, a novel tri-nuclear platinum complex, forms long-range DNA adducts and is highly potent when compared with cisplatin in vitro. Preclinical studies demonstrated activity in cisplatin-resistant tumours and tumours with mutated p53 status. Phase I & II clinical studies gave preliminary indications of activity in melanoma, pancreatic, lung and ovarian cancers. The aim of this study was to determine the efficacy and confirm the toxicity of BBR3464 when given either as first- or second-line treatment for advanced disease in patients with gastric and gastro-oesphageal adenocarcinoma. Two multicentre, open label, Gehan design studies were conducted; one study used BBR3464 as first-line and the other as second-line treatment for metastatic or locally advanced disease. Nineteen first-line and 26 second-line patients were enrolled receiving a total of 74 and 53 infusions, respectively. Initially, seven patients in the second-line study received BBR3464 using the planned schedule of 1.1 mg/m2 every 4 weeks; however, 5 of these patients experienced dose-limiting grade 3 or 4 febrile neutropenia; subsequent patients in both studies were treated using the modified schedule of 0.9 mg/m2, every 21 days. In 1 of 17 evaluable, previously untreated patients, regression of multiple skin lesions was noted with stabilisation of lung metastases and maxillary sinus mass, lasting 155 days. In the first-line study, the median time to progression was 85 days [95% Confidence Interval (CI): 42, 127] (2.8 months) and in the second-line study, the median time to progression was 71 days [95% CI: 42, 109] and 38 days [95% CI: 32, 73] in the 1.1 and 0.9 mg/m2 dose level groups, respectively. Toxicity data were available for 45 patients. Neutropenia was the main toxicity seen (G3: 40%, G4: 40%). Febrile neutropenia was observed in six patients (15%) treated with 0.9 mg/m2 compared with five patients (71%) treated with 1.1 mg/m2 BBR3464. Other drug-related toxicities (G3/4) included: anaemia, thrombocytopenia, nausea, vomiting, diarrhoea, mucositis and fatigue. Diarrhoea and nausea/ vomiting were adequately controlled by the use of loperamide and antiemetics, respectively. Recruitment to the second-line study was closed early due to the poor response rate (1/17 evaluable, 6%; 95% CI: 1%, 27%) and short time to progression noted in the first-line study. Further studies with BBR3464 in this tumour type are not recommended.
 ...
PMID:Phase II studies of BBR3464, a novel tri-nuclear platinum complex, in patients with gastric or gastro-oesophageal adenocarcinoma. 1528 89

The intraductal tubular adenoma (ITA), pyloric gland type, of the pancreas is an uncommon benign tumor, akin to the pyloric gland type adenoma of the gallbladder. We report 6 cases of ITA of the pancreas: 3 male and 3 female aged 50 to 79 years (mean, 63.5 years; median, 65 years); all were examined clinicopathologically. Four patients showed no symptoms, but appetite loss and/or general fatigue presented in two. Grossly, all tumors formed a localized polypoid mass protruding into the lumen of the dilated pancreatic duct. Five of the six tumors were found within the main duct, and the other arose within the branch duct of the pancreas. Microscopically, the tumors were composed of closely packed tubular glands resembling pyloric type glands. They were lined by columnar or cuboidal epithelial cells with foci of mild to moderate dysplastic change. In 2 cases, the adjacent pancreas showed foci of intraductal papillary-mucinous adenoma. Histochemically, the tumors largely showed neutral mucin with a lesser amount of acidic mucin made up mainly of sialomucin. Endocrine cells were found in five tumors. Immunohistochemically, all tumors were labeled with M-GGMC-1 and MUC6, whereas MUC1 and MUC2 stains were negative. Pepsinogen II was positive in 5 tumors; thus, the results displayed a pattern of differentiation similar to those of ordinary gastric pyloric or metaplastic pyloric glands. DPC4 expression was maintained in all tumors and p53-positive nuclei were hardly encountered. All patients are alive with no evidence of disease 3 to 10.5 years after surgical resection.
 ...
PMID:Intraductal tubular adenoma of the pancreas, pyloric gland type: a clinicopathologic and immunohistochemical study of 6 cases. 1583 84

BBR 3464 is a novel triplatinum compound that has exhibited anti-tumor activity in both cisplatin-sensitive and cisplatin-resistant, as well as in p53 mutant tumor models. In phase I testing, the dose-limiting toxicities have included myelosuppression and diarrhea. Both an intermittent (day 1 every 21-28 days) and a continuous (dailyx5 days) schedule have been studied, and the intermittent schedule has been chosen for further development. The primary objective of this study was to assess the efficacy of BBR 3464 administered at a dose of 0.9 mg/m i.v. over 1 h every 21 days in patients with small cell lung cancer who have progressed after first-line therapy. Pharmacokinetic analysis was also performed and will be reported. Patients were stratified based on prior response into resistant and sensitive (response duration 3 months or longer) subgroups. Thirty-seven patients were enrolled onto this multicenter study. The median number of cycles delivered was 2 in the resistant subgroup (range 1-12) and 3 in the sensitive subgroup (range 1-8). Most common grade 3/4 hematological toxicities included neutropenia (62%), febrile neutropenia (16%), anemia (10%), fatigue (5%) and hypokalemia (5%). Although no objective responses were seen in 34 evaluable patients, 11 patients (32%) had disease stabilization (four resistant/seven sensitive) with 23 patients (68%) experiencing continued disease progression (12 resistant/11 sensitive). Median time to progression was 53 days in the resistant subgroup [95% confidence interval (CI) 37-63] and 66 days in the sensitive subgroup (95% CI 51-136). The median and 1-year survival rate based on subgroup was 78 (resistant) (95% CI 56-165) versus 209 days (sensitive) (95% CI 83-296) and 6 (resistant) (95% CI 0-17) versus 20% (95% CI 2-38%), respectively. We conclude that the toxicity profile of BBR 3464 in this phase II trial is consistent with the phase I experience. The lack of activity in either patient subgroup, however, does not support further evaluation of this drug as a single agent in this disease.
 ...
PMID:Phase II study of BBR 3464 as treatment in patients with sensitive or refractory small cell lung cancer. 1691 15

We describe a patient who underwent thoracic radiation therapy for biopsy-proven pulmonary spindle cell sarcoma in the left lower lobe, 15 months after birth. At the age of 37 she developed shoulder pain, fatigue, and progressive exertion dyspnoea. Chest X-ray revealed a pulmonary mass in the left lower lobe due to a cytology-proven malignant tumour.The patient underwent left pneumonectomy. Histology revealed a myosarcoma of the lung, similar to the previous sarcoma. Furthermore, the patient was diagnosed to have Turner syndrome mosaic and chromosomal analysis revealed a translocation t(1;13) in 3/50 metaphases. However a germline mutation of the p53 tumour suppressor gene was excluded. After 2 years of follow-up the patient is stable and there are no signs of recurrence of the tumour.We conclude a re-occurrence of this very rare malignant disorder of the lung after a 36-year interval in a patient with Turner syndrome mosaic. Following initial curative radiation therapy, with a remission over 36 years, lung resection was now successfully performed.
 ...
PMID:Successful resection of a re-occurred pulmonary myosarcoma in a patient with turner syndrome mosaic. 1852 51

Inflammatory bowel disease (IBD) includes two similar yet distinct conditions called ulcerative colitis (UC) and Crohn's disease (CD). These diseases affect the digestive system and cause the inflammation of intestinal tissue, form sores and bleed easily. Most children with IBD are diagnosed in late childhood and adolescence. However, both UC and CD have been reported as early as in infancy. Most information pertaining to the epidemiology of IBD is based upon adult studies. Symptoms include abdominal pain, cramping, fatigue and diarrhea. Genetic factors play a significant role in determining IBD susceptibility. Epidemiological data support a genetic contribution to the pathogenesis of IBD. Recently, numerous new genes have been identified as being involved in the genetic susceptibility to IBD: TNF-308A, CARD15 (NOD2), MIF-173, N-acetyltransferase 2 (NAT2), NKG2D (natural killer cell 2D), STAT6 (signal transducer and activator of transcription 6), CTLA-4 (cytotoxic T lymphocyte antigen-4), MICA-MICB (major histocompatibility complex A and B), HLA-DRB1, HLA class-II, IL-18, IL-4, MICA-A5, CD14, TLR4, Fas-670, p53 and NF-kappaB. The characterization of these novel genes has the potential to identify therapeutic agents and aid clinical assessment of phenotype and prognosis in patients with IBD (UC and CD).
 ...
PMID:Epidemiology and gene markers of ulcerative colitis in the Chinese. 1923 40

We describe a 79-year-old patient who presented with fatigue, weight loss, pancytopenia and a papular exanthem. Previous attempts to taking bone-marrow biopsies had resulted in a 'dry tap', with no material collected, suggesting idiopathic myelofibrosis. Histological examination of skin biopsies showed dermal infiltration of monocytoid cells, resulting in a diagnosis of acute myeloid leukaemia (French-American-British M5 morphology) with leukaemia cutis (LC). Numerous abnormalities of chromosome 8 (trisomy or tetrasomy) have been identified in association with LC. We performed fluorescent in situ analysis on cutaneous tissue using directly labelled probes for various gene loci often involved in patients with AML; these tests showed deletion of p53 and excluded trisomy 8. However, application of probes for AML/ETO, MYC and telomere 8q revealed a gain at 8q22/8q24/8q telomere in a significant number of infiltrating cells. We hypothesize that a partial gain at 8q rather than trisomy of the whole chromosome 8 exhibits an association with LC in AML.
 ...
PMID:Papular exanthem discloses acute myeloid leukaemia: interphase fluorescence in situ hybridization revealed deletion of p53 and gain at 8q22/8q24/Tel8q without trisomy 8. 1943 43

Cyclins and cyclin-dependent kinases (CDK) form a key part of the regulatory proteins that govern the cell cycle. Aberrancy in their function can lead to uncontrolled growth and proliferation of the cells which forms the basis of many human diseases, especially cancers. Seliciclib (CYC202, R-roscovitine) is a second-generation CDK inhibitor that competes for ATP binding sites on these kinases, reducing tumor growth and inducing cell death. It is a direct inhibitor of cyclin E/CDK2 and also has inhibitory effects on cyclin H/CDK7 and cyclin T/CDK9. Seliciclib leads to growth arrest and apoptosis of cell lines through activation of the p53 gene, inhibition of RNA processing and blockage of the RNA polymerase II-dependent transcription, and reduction of anti-apoptotic proteins. Seliciclib has good oral bioavailability, although its absorption is slowed by food. It is distributed rapidly to the body tissues and metabolized rapidly to a carboxylated derivative that is excreted by the kidneys. The major adverse effects of seliciclib are electrolyte disturbances (hypokalemia, hyponatremia), gastrointestinal side effects (nausea, emesis, anorexia), fatigue, transient hyperglycemia, elevation of liver enzymes and reversible elevation of serum creatinine. At present, it is in Phase II trials for non-small cell lung cancer and nasopharyngeal carcinoma.
 ...
PMID:Seliciclib in malignancies. 1993 6

Nitric oxide (NO) may aggravate neuronal damage after spinal cord injury (SCI). We hypothesized that NO produced by inducible nitric oxide synthase (iNOS) accelerates secondary damage to spinal tissue, which may be reversed by the neuroprotectant, melatonin. This study investigated the effects of combination therapy with melatonin (10 mg/kg) and exercise (10 m/min) on recovery from SCI caused by contusion. We examined locomotor recovery, iNOS gene expression, autophagic and apoptotic signaling, including Beclin-1, LC3, p53 and IKKalpha protein expression and histological alterations in the ventral horn of the spinal cord. Melatonin in combination with exercise resulted in significantly increased hindlimb movement (P < 0.05), a reduced level of iNOS mRNA (P < 0.05) and more motor neurons in the ventral horn, versus control SCI and SCI plus exercise alone, with no effect on the other signaling molecules examined. This study shows that combined therapy with melatonin and exercise reduces the degree of secondary damage associated with SCI in rats and supports the possible use of melatonin in combination with exercise to reduce the side effects related to exercise-induced fatigue and impairment.
 ...
PMID:Synergistic effect of melatonin on exercise-induced neuronal reconstruction and functional recovery in a spinal cord injury animal model. 2021 Aug 55


1 2 3 4 5 Next >>