Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Phase II studies of BBR3464, a novel tri-nuclear platinum complex, in patients with gastric or gastro-oesophageal adenocarcinoma. 1528 89

A 62-year-old man was admitted with chief complaints of fever and general fatigue. Enhanced computed tomography revealed a tumor (5 cm in diameter) in the right suprarenal space, and the right renoportal lymph nodes were swollen. An abdominal TI-weighted MR image showed a low-intensity tumor measuring 4.5 x 5.5 x 6.0 cm. Chest computed tomography revealed two tumors. One was 1.5 cm, on the hilum of left lung, the other was 1 cm in the S6 lung field near the pleura. These findings strongly indicated primary adrenal carcinoma and lung metastasis. Right adrenalectomy was performed. Histological examination of this tumor revealed diffuse tumor cells with irregular nuclei, and it was diagnosed as poorly differentiated adenocarcinoma. There was no possibility of primary adrenal carcinoma. The primary site of the tumor was suspected to be the left lung.
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PMID:[Metastatic adrenal carcinoma suspected as a primary tumor: a case report]. 1533 91

Lung cancer is still the most frequently seen malignancy among males where as females are less affected. Recently the lung cancer prevalence has been reported to increase among females in parallel to the increment in cigarette consumption. In our 2 clinic 11.2% (44 cases) of 393 primary lung cancer cases between 1993-1997 were female. We evaluated the demographical characteristics and yearly distribution of our female patients. Mean age was 64+/-12.1 and 18.2% of the patients were smokers. The main complaints were dyspnoea (59%), chest pain (57%), fatigue (47%), cough (45%)and sputum production (32%). The cell type distribution rates were as follows;adenocarcinoma 45.4%, squamous cell cancer 29.5%, small cell cancer 20.5% and large cell cancer 4.6%. The diagnostic methods used were sputum cytology (27.3%),transbronchial biopsy and lavage (38.6%), thoracocentesis and pleural biopsy (15.8%),transthoracic fine needle aspiration (13,6%) and open lung biopsy (4.7%). As a result,we found a low percentage of smokers but a high rate of adenocarcinomas among our female patients.
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PMID:Does the primary Lung Cancer rate increase among females? 1556 64

Cancer cachexia is a syndrome of weight loss, muscle wasting, fatigue, and anorexia that occurs in patients with advanced or recurrent solid tumor disease. Tumor necrosis factor-alpha (TNFalpha) and prostaglandin E2 (PGE2) have been implicated in the biology of cachexia and serve as possible targets for treatment of this condition. Conjugated linoleic acid (CLA) is a polyunsaturated fatty acid that alters the synthesis of PGE2 and reduces the negative effects of TNF on body weight of healthy mice. We hypothesized that a diet supplemented with .5% CLA might reduce muscle wasting in mice bearing the colon-26 adenocarcinoma, an animal model of cancer cachexia. CLA preserved gastrocnemius muscle mass and reduced TNF receptors in muscle of tumor-bearing mice. These data suggest that CLA may preserve muscle mass by reducing the catabolic effects of TNF on skeletal muscle.
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PMID:Conjugated linoleic acid preserves gastrocnemius muscle mass in mice bearing the colon-26 adenocarcinoma. 1562 11

A 55-year-old man presented with tumor microembolism manifesting as characteristic patterns of pulmonary perfusion on lung scanning. He had a 2-week history of dyspnea and general fatigue. Echocardiography demonstrated right ventricular enlargement. Computed tomography of the chest was normal. Lung perfusion imaging showed multiple subsegmental peripheral defects, which were characteristic of tumor embolism. Ultrasonography and computed tomography of the abdomen revealed multiple enlargement of the lymph nodes. Upper gastrointestinal panendoscopy showed gastric cancer. At 10 days after admission, he suffered cardiac arrest and died despite resuscitative efforts. Histological examination revealed pulmonary arterial obstruction with tumor cells, and poorly differentiated adenocarcinoma in the stomach and lymph nodes. This case emphasizes the need to include tumor microembolism in the differential diagnosis of dyspnea, even if there is no evidence of an underlying malignant tumor.
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PMID:[Tumor microembolism presenting as characteristic patterns of pulmonary perfusion on lung scanning: a case report]. 1570 Sep 28

A 54-year-old woman with a history of fatigue and shortness of breath was found to have a pericardial effusion and mild mediastinal lymphadenopathy. Video-assisted pericardioscopy revealed thickened pericardium studded with multiple nodules. Histologically the tumor was diagnosed as papillary adenocarcinoma. The site of the primary tumor could not be identified. As lung cancer is one of the most frequent causes of pericardial metastases the patient was treated with cisplatin and vinblastin. Following 5 courses of chemotherapy--given over a 4 month period--the amount of pericardial effusion and pericardial thickness did not change. The material from pericardial biopsy was reexamined and positive immunostaining for calretinine was found. The final diagnosis was primary pericardial mesothelioma of epithelioid type. Palliative radiotherapy of mediastinum was planned but the patient deteriorated and died due to disease progression with venous thrombosis and superior vena cava syndrome. The case illustrates the difficulties in establishing diagnosis of primary pericardial mesothelioma which is a rare tumor with poor prognosis.
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PMID:[Diagnostic difficulties in primary mesothelioma]. 1575 64

Patients with adenosquamous carcinoma of the gallbladder tend to present with a bulky tumor that frequently displays involvement with adjacent organs, and diagnosis is usually made at an advanced stage. This may contribute to the poor prognosis of patients with adenosquamous carcinoma of the gallbladder compared to patients with adenocarcinoma. We present herein a patient with advanced adenosquamous carcinoma of the gallbladder who is doing well with no evidence of recurrence more than 5 years after radical resection. A 72-year-old woman complaining of generalized fatigue and loss of appetite was referred to our hospital with suspected cholelithiasis, following ultrasonography done at another hospital. On admission, abdominal ultrasonography and computed tomography revealed an irregularly shaped solid mass extending from the fundus of the gallbladder, and invasion of the stomach was strongly suspected. Gallbladder carcinoma was diagnosed, and radical resection, including partial gastrectomy, was performed. Histopathologically, adenosquamous carcinoma was diagnosed, and it was graded as si, hinf0, binf0, pv0, a0, t4, n0, and stage IVa.
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PMID:Long-term survival of a patient with advanced adenosquamous carcinoma of the gallbladder after radical resection. 1586 80

Capecitabine and docetaxel have single-agent activity in upper gastrointestinal tumours, and have together demonstrated preclinical synergy and a survival benefit in breast cancer, and high response rates in first-line metastatic gastric cancer. This trial assessed the efficacy, safety and feasibility of capecitabine in combination with docetaxel in patients with metastatic oesophageal cancer. In all, 24 patients with advanced disease (17 squamous cell carcinoma and seven adenocarcinoma) received oral capecitabine (1000 mg m(-2) twice daily on days 1-14) plus intravenous docetaxel (75 mg m(-2) on day 1) every 3 weeks as first- (n = 16) or second-line (n = 8) therapy. Patients received a median of four cycles of treatment (range, 0-6). The median follow-up is 16.5 months (range, 7.9-21.4 months). Intent-to-treat efficacy analysis showed an overall response rate of 46%. Of the 11 responders (one complete and 10 partial), nine of 16 (56%) received first-line and two of eight (25%) received second-line therapy. The median time to progression was 6.1 months (95% confidence interval (CI), 4.5-7.7 months). The median survival was 15.8 months (95% CI, 7.8-23.9 months). Severe adverse events (grade 3/4) reported were: neutropenia (42%, including febrile neutropenia 8%), hand-foot syndrome (29%), diarrhoea (13%), sensory neuropathy (13%), anaemia (8%) and fatigue (8%). Capecitabine plus docetaxel has a manageable adverse event profile and very promising activity in metastatic oesophageal cancer, at least comparable to other doublet regimens. Therefore, the combination merits further investigation in this setting.
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PMID:Capecitabine plus docetaxel every 3 weeks in first- and second-line metastatic oesophageal cancer: final results of a phase II trial. 1594 31

Protein-losing gastropathy due to diffuse varioliform gastritis is a rare condition, and its occurrence accompanying ampullary carcinoma is particularly rare. We report here a case of ampullary carcinoma accompanied with protein-losing gastroenteropathy due to diffuse varioliform gastritis. A 39-year-old Japanese woman was admitted to our hospital because of general fatigue and generalized edema. Her total protein level was 3.1g/dL, with an albumin level of 1.4g/dL, and hemoglobin level of 6.9g/dL. Upper gastrointestinal endoscopic examination showed diffuse varioliform gastritis and carcinoma of the papilla of Vater. A diagnosis of protein-losing gastropathy was made based on the results of scintigraphy using technetium 99m-labeled human albumin. Continuous bleeding from ampullary carcinoma caused anemia and deteriorated hypoproteinemia. Pancreaticoduodenectomy was performed for ampullary carcinoma prior to Helicobacter pylori eradication. The tumor was a papillary adenocarcinoma, which had invaded the lamina muscularis propria over the sphincter of Oddi; the resected stomach revealed typical hyperplastic lymphocytic gastritis. H. pylori were detected on microscopic analysis. Scintigraphy after surgery showed no accumulation of the tracer in the bowel. Anemia, hypoalbuminemia and diffuse varioliform gastritis are improved 6 months after surgery and H. pylori eradication, and the patient is currently free from disease.
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PMID:Ampullary carcinoma associated with protein-losing gastropathy due to diffuse varioliform gastritis. 1600 48

Palliative chemotherapy for inoperable/metastatic oesophageal cancer has limited activity. This study assesses the feasibility and activity of gemcitabine and cisplatin in this group of patients. In total, 42 patients with locally advanced/metastatic squamous or adenocarcinoma of the oesophagus were treated with gemcitabine 1250 mg m(-2) days 1 and 8 and cisplatin 75 mg m(-2) day 1 in a 21-day cycle. Interim safety analysis was carried out after the first 19 patients suggested significant toxicity. The dose of gemcitabine was subsequently reduced to 1000 mg m(-2). Patients were assessed for toxicity and response. The median number of treatment cycles per patient was 4 (range 1-6). Grade 3-4 neutropenia occurred in 37% of cycles; however, there was only one episode of neutropenic fever. Nonhaematological toxicities included fatigue, nausea and vomiting. Among 32 patients eligible for response, there were three complete responses and 16 partial responses (overall response rate of 45%); nine patients had stable disease. Median survival was 11 months. The response rate appears to be greatest in those with squamous carcinoma compared to adenocarcinoma (71 vs 33%, P=0.036). The combination of gemcitabine and cisplatin in this schedule has manageable toxicity and significant activity in patients with locally advanced/metastatic oesophageal cancer and is worthy of further study.
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PMID:Phase II study of gemcitabine and cisplatin in locally advanced/metastatic oesophageal cancer. 1627 60


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