Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Special features which enable preoperative differential diagnosis are dealt with in detail with reference to 44 patient with carcinoid of the digestive tract. Carcinoid of the appendix becomes noticable early with signs of acute or chronic appendicitis and in 94% of cases is operated on in good time. Angiography of the superior mesenteric artery shows a characteristic stellate figure in the mesenterium in carcinoid of the small intestine. In contrast to the primary tumor, liver metastases show intense vascularization in the angiogram. A rise in urinary excretion of 5-hydroxyindole acetic acid is pathognomonic for carcinoid, its determination permits the checking of operative radicality and shows the appearance of metastases early.
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PMID:[Carcinoid of the digestive tract. Diagnostic possibilities (author's transl)]. 10 77

This phase I study investigated flavone acetic acid (FAA) given as a 12-h intravenous infusion every 3 weeks in the absence of urinary alkalinisation. Cohorts of three patients were treated at doses of 7, 10 and 13 g/m2. One subject had colon cancer; 5, renal cancer; and 3, lung cancer. The Eastern Cooperative Oncology Group (ECOG) performance status was 0 in four patients, 1 in two subjects and 2 in three cases. The maximum tolerated dose was 13 g/m2. The dose-limiting toxicities were WHO grade 3 hypotension and grade 3 diarrhoea. Other toxicities included lethargy and dizziness, nausea, temperature fluctuation, myalgia and dry mouth, but no significant myelosuppression was encountered. One patient receiving 10 g/m2 for renal cancer showed a partial response that lasted for 3 months and included the resolution of pulmonary and cutaneous metastases. The pharmacokinetics showed large interpatient variability. At 12-16 h post-infusion, the plasma elimination profile entered a plateau phase, with frequent increases in concentration suggesting enterohepatic recycling. Neither peak FAA levels nor AUC values were dose-dependent at the doses studied. Peak plasma levels were 101-402 micrograms/ml and AUC (0-48 h) values were 75-470 mg ml-1 min. Plasma protein binding varied with total concentration. Two metabolites were detected in the plasma, and both also underwent apparent enterohepatic recycling. Repeat dosing resulted in decreases of up to 48% in peak levels and AUC values for FAA in three of six patients. Of the total FAA dose, 39%-77% was excreted in the urine as FAA or metabolites within 2 days. The dose recommended for further phase II studies is 10 g/m2.
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PMID:A phase I and pharmacokinetic study of 12-h infusion of flavone acetic acid. 155 Nov 73

Metastatic renal cell carcinoma (RCC) remains largely incurable. We used a murine RCC (Renca) in BALB/c mice to investigate the treatment possibilities with chemoimmunotherapy using in vivo boosters of natural killer (NK) activity. Diffuse pulmonary metastases were induced by intravenous (i.v.) inoculation with 100,000 Renca cells. All untreated control animals died within one month from pulmonary metastases. Chemoimmunotherapy using the NK immunostimulator flavonic-8-acetic acid (FAA) at 200 mg./kg. i.v. was given on the third day post tumor inoculation, followed by four consecutive days of twice daily intraperitoneal (i.p.) administration of 10,000 units human recombinant interleukin-2 (rIL-2). This chemoimmunotherapy regimen consistently cured 70% of tumor-bearing animals. Mice cured by this chemoimmunotherapy regimen did not reject subsequent reinoculation with Renca, indicating absence of specific antitumor immunity as a result of the treatment. While FAA and rIL-2 have no demonstrable in vitro cytotoxicity for Renca, they are excellent boosters of in vivo NK activity. These data suggest a potential alternative treatment method for metastatic RCC, a tumor type for which no efficient cytostatic drugs are available.
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PMID:Chemoimmunotherapy of metastatic murine renal cell carcinoma using flavone acetic acid and interleukin 2. 155 7

Conventional treatment of cancer, especially for patients with metastatic melanoma tumor, is often ineffective. Immunotherapy and recently introduced gene therapy have revolutionized the treatments of patients with metastatic melanoma tumor. Use of biological response modifiers, such as interleukins and interferons, have been found to enhance therapeutic benefits to patients with malignant melanoma. Initial studies with a high-dose interleukin-2 (IL-2) therapy have proved effective in patients with melanoma tumor, although a variety of systemic toxicities were observed. A low-dose IL-2 continuous infusion has shown a similar response in patients with melanoma tumor, but produced lesser toxicity. The low-dose IL-2 therapy has been studied with an adoptive transfer combined with either autologous lymphokine activated killer cells or autologous tumor infiltrating lymphocytes (TIL). IL-2 in combination with chemotherapeutic agents such as flavone acetic acid, dacarbazine, and cyclophosphamide have also been studied in patients with metastatic melanoma. Results have shown a moderate response in patients with metastatic melanoma. TIL therapy, however, has been shown to result in higher objective regression due to potent tumor-specific killing and tumor-specific targeting characters of the TIL. The tumor targeting nature of the TIL creates the possibility of using TIL as a vehicle to deliver gene product specifically to tumor tissue. Safety and toxicity of gene-transduced TIL were addressed by the use of neomycin-resistant, gene-transduced TIL in patients with metastatic melanoma. We also investigated the use of vaccinia oncolysate therapy by using the viral oncolysate prepared with IL-2 gene encoded vaccinia virus. Preliminary studies with murine hepatic metastases colon model have shown encouraging results.
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PMID:Prospects for gene therapy and lymphokine therapy for metastatic melanoma. 164 99

A patient with carcinoid syndrome was treated with the somatostatin analogue (SMS 201-995). The drug significantly improved the symptoms of the patient, flushing and diarrhea, and reduced urinary excretion of 5-hydroxyindole acetic acid. However, hepatic metastases remained unchanged. Clinical or biochemical adverse effects were not present during the treatment period.
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PMID:[A favorable response to the somatostatin analog SMS 201-995 in a patient with the carcinoid syndrome]. 154 39

A murine monoclonal antibody directed against carcinoembryonic antigen (CEA) was labeled with indium-111 (111In) by means of a benzylisothiocyanate derivative of diethylenetriamine penta-acetic acid (DTPA) and used for clinical radioimmunodetection studies. Twenty-one patients having a history of surgically resected colorectal cancer and rising serum CEA levels suggestive of tumor recurrence were studied. Patients were infused over 20 minutes with 5, 10, or 20 mg of the monoclonal antibody labeled with 5 mCi of 111In. The mean radiochemical purity was greater than 96%. No toxicity was seen. The stability of the radiolabel on antibody in patient serum was demonstrated by high-performance liquid chromatography (HPLC), sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) with autoradiography, and immunoprecipitation for up to 96 hours after infusion. Tumor sites were identified in 20 of 21 patients. Sites of antibody accumulation in 20 patients were confirmed as tumor either by resection at laparotomy (16 patients) or fine-needle biopsy (four patients). Nine patients who had the identified lesion resected or irradiated showed return of the serum CEA antigen level to normal or near normal values. In the absence of high levels of circulating CEA (greater than 500 ng/mL), the disappearance of radioactivity from patient serum demonstrated first order elimination kinetics, with a mean half-life of 38 hours. The serum half-life was not affected by the dose of antibody administered or by serum CEA titers below 500 ng/mL. Despite a mean liver uptake of 18% injected dose (ID) 24 hours after administration, hepatic metastases were easily visualized as areas of increased uptake of radioactivity. Radioimmunodetection of recurrent colorectal cancer, not detected by computed tomographic (CT) scans, appears achievable with this agent. This may allow successful clinical intervention in selected patients.
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PMID:Initial clinical study of indium-111-labeled clone 110 anticarcinoembryonic antigen antibody in patients with colorectal cancer. 206 59

Ten patients with hepatic metastases from islet cell tumors or carcinoid tumors had clinical symptoms from hormonal secretion and/or pain related to the mass effect of neoplastic liver involvement. Hepatic arterial embolization (HAE) using radiographically guided catheters to inject thrombogenic material was applied to the right and/or left hepatic arteries separately 5 to 7 days apart. All ten patients improved within days of the procedure as confirmed by a decrease in measurable hormone levels (gastrin, adrenocorticotropin, and 5-hydroxy indole acetic acid) or by a decrease in tumor size and improved symptoms. Three patients underwent repeated reembolization from two to four times over nine to 50-month intervals for symptom control. Complications of and indications for HAE in these patients are discussed. It appears to be an effective treatment for dealing with the hormonal syndromes and local symptoms related to the hepatic metastases of hormone-secreting tumors.
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PMID:Hepatic arterial embolization for metastatic hormone-secreting tumors. Technique, effectiveness, and complications. 216 Dec 78

Recombinant interleukin 2 (rIL-2) and flavone acetic acid (FAA) were used to treat 34 patients with progressing metastatic melanoma. Five patients had solely non-visceral disease and the median number of organ sites involved was two. Five doses of rIL-2 were given, the first dose intrasplenically via a femoral artery catheter with a further dose 4 h later i.v. and the other doses i.v. on alternate days. The rIL-2 dose was 11 x 10(6) Cetus units m-2; the day before rIL-2, FAA (4.8 G m-2) was given as a 6 h i.v. infusion, in order to enhance further killer cell activity. A total of three courses at 21-day intervals was planned and 74 courses in all were given. Despite the high dose of rIL-2 and the potential overlapping toxicity affecting blood pressure with the addition of FAA, side-effects were generally mild. There were only five episodes of grade 4 toxicity: one of ventricular tachycardia and four other episodes of transient biochemical or haematological disturbance. Grade 3 hypotension or hypertension occurred on 22 courses but again was transient. No patient required intensive care facilities. Five patients had tumour response, one being complete. Responses occurred in pulmonary and hepatic metastases, but mainly in non-visceral sites. Eleven patients remain alive at 6-17 months and in five there is no relapse or progression of disease. Despite the impressive results in animal tumour models, the addition of FAA to rIL-2 in the present study has not markedly improved results over rIL-2 alone.
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PMID:Recombinant interleukin-2 (rIL-2) with flavone acetic acid (FAA) in advanced malignant melanoma: a phase II study. 233 47

A transcatheter embolisation was carried out for treatment of a patient suffering from hepatic metastases of a malignant carcinoid tumour. Recurrent and very severe carcinoid symptoms could be observed; a bronchial carcinoid supposingly the primary tumour without characteristic symptoms was removed six years before. The carcinoid symptoms became resistant to pharmacological agents and finally ended in life-threatening clinical complications. The transcatheter hepatic artery embolisation was successfully performed and repeated three months later. After embolisation relief of carcinoid symptom and a significant decrease in 5-hydroxyindole acetic acid (5-HIAA) urinary excretion lasting for eight months could be observed. There were no serious complications with adequate pharmacological cover, however, a transient fever, leucocytosis, abdominal pain and an increase in serum transaminase activities occurred after the procedure. The transcatheter hepatic artery embolisation should be a method of choice for treatment of patients with carcinoid metastases producing severe carcinoid symptoms resistant to pharmacological agents.
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PMID:Hepatic artery embolisation--new approach for treatment of malignant carcinoid syndrome. 242 13

The effect of a 550-kcal mixed meal and of an intravenous injection of pentagastrin (0.06 microgram/kg body wt) upon peripheral blood serotonin concentrations has been compared in 10 carcinoid patients with hepatic metastases and healthy subjects. The fasting concentrations of blood serotonin in the patients (range 790-4500 ng/ml) were elevated compared with healthy subjects (range 71-310 ng/ml; n = 15). Urinary output of 5-hydroxyindole acetic acid was elevated in 8 patients but was in the healthy range for 2 patients. The healthy subjects (n = 9) responded to food with an increase in blood serotonin (maximum rise over mean basal of 32% +/- 4%) that was significant at 60, 75, 90, and 105 min postcibal. All carcinoid patients responded to food with a comparable (25% +/- 11% over basal) rise in serotonin but the pattern of release was erratic. All patients with tumor metastases exhibited symptoms of the carcinoid flush after eating, but there was no correlation between occurrence and severity of the flush and occurrence and magnitude of the rise in serotonin. Intravenous pentagastrin evoked a flush in all carcinoid patients, but there was no significant increase in peripheral blood serotonin either in the patients or in healthy subjects.
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PMID:Serotonin release into blood after food and pentagastrin. Studies in healthy subjects and in patients with metastatic carcinoid tumors. 242 55


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