Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.73 (urokinase-type plasminogen activator)
 10,685 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 63-year-old female, who had undergone sigmoidectomy for sigmoid carcinoma one year before, was admitted for multiple liver metastases. A urokinase-immobilized catheter was introduced into the proper hepatic artery via the gastroepiploic artery operatively. A daily arterial infusion of 5-FU (250 mg) was combined with a weekly arterial infusion of adriamycin (30 mg) or MMC (10 mg). After discharge, 5-FU (200 mg/day) was given orally and MMC (10 mg) was infused intraarterially every other week at an outpatient clinic. ADR or MMC was infused with angiotensin II, known to increase arterial blood supply to a malignant lesion. Ultrasonography demonstrated 35 to 50% reduction in tumor diameter. The density of metastases seen in computerized tomography became low indicating tumor necrosis. Plasma CEA level, which had initially been as high as 864 ng/ml, decreased rapidly and has remained within normal limits up to the present time. Arterial infusion chemotherapy using 5-FU, ADR or MMC in combination with angiotensin II seems to be effective in the treatment of multiple hepatic metastases from colorectal carcinoma.
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PMID:[A case of multiple liver metastases from sigmoid carcinoma treated successfully with arterial infusion chemotherapy]. 308 78

We studied effects of urokinase (Uronase) on the transfer of an oral anticancer agent, 1-hexylcarbamoyl-5-fluorouracil (HCFU) into blood, bile and pancreatic juice in 5 patients in whom pancreaticoduodenectomy has been performed for cancer of the periampullary region, and who had been simultaneously provided with drainage of the bile duct and pancreatic duct. Following oral administration of 500 mg of HCFU, HCFU and 5-FU concentrations in blood reached a peak at 2 hours, those in bile at 4 hours, and those in pancreatic juice at 4 to 6 hours. The administration of 24,000 IU of urokinase in combination with HCFU resulted in increased HCFU and 5-FU concentrations in blood, bile and pancreatic juice--the HCFU concentration in bile increased to 3 times and that in pancreatic juice, to about 5 times the level in the some counterparts in urokinase--untreated patients. These changes seemed to have resulted from the acceleration by urokinase of distribution of the anticancer agent into the organs.
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PMID:[Effects of urokinase on the transfer of 1-hexylcarbamoyl-5-fluorouracil (HCFU) into the blood, bile and pancreatic juice]. 406 12

Eighty three patients suffering from brain tumors have been treated by anticancer pellets containing 5-FU, urokinase, mitomycin and BUdR in dimethylsiloxan (Silastic) for three years. Constant and prolonged release of the chemicals from the anticancer pellet had already been proved in vitro. The amount of daily release were 1-3/1,000 of original volume. Tissue concentration of 5-FU was measured by bioassay system using staphylococcus 209 P strain with plate dilution method. In spite of the rapid disappearance of serum 5-FU, the local high accumulation of 5-FU was demonstrated in vivo. In rat neurogenic tumor, 1.104 microgram/g was detected on 60 days after the application of anticancer pellet containing 500 mg of 5-FU. The growth of tumor was also suppressed. The clinical study consists of 83 patients, 30 of glioblastoma, 19 of metastatic brain tumor, 13 of astrocytoma, 7 of oligodendroglioma, 4 of ependymoblastoma, 4 of malignant lymphoma and 6 of others. The median survival time of gliblastoma was prolonged to 71.5 weeks by the implantation of anticancer pellet from 40 weeks of control group. However, the median survival time of astrocytoma and metastatic brain tumor were 24 and 6 months, respectively, which have no significant difference from control groups. In the patients of metastatic brain tumor, the regrowth of metastatic foci in the brain was completely suppressed. However, most of them were succumbed from the original tumors. The concentration of 5-FU in several human tissue was measured in ten patients with different time intervals after the implantation of the anticancer pellet. Although they have different histologic patterns, the concentrations of 5-FU in human brain tumors were ranged from 0.05 to 0.67 microgram/g by 14 months after the implantation of the anticancer pellet. The adjacent cystic fluids also contain from 0.62 to 4.9 microgram/ml of 5-FU for two years. These results mean that they are keeping higher level of 5-FU than the tumoricidal level of 5-FU (0.056 microgram/g) for more than two years. On the other hand, no respective accumulation was demonstrated in other tissues. None of the patients showed any adverse reactions except a continuous slight fever up to 38 degrees C.
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PMID:[Treatment of brain tumors with anticancer pellet--experimental and clinical study (author's transl)]. 709 76

A 65-year-old male underwent iliocecal excision and hepatic posterior segmentectomy for cecum cancer and synchronous liver hepatic metastasis in September and October 2001, respectively. A reservoir was implanted by the GDA-coil method from the right femoral artery in November, and WHF (5-FU 1,000 mg/m2) was administered 8 times. Because of the remnant liver recurrence, WHF was restarted in April 2002. Left leg paralysis appeared suddenly after the 3rd administration. Heparin and urokinase were administrated continuously after hospitalization. Also, liver function tests showed a worsening condition. The bile duct necrosis in the liver was examined with abdominal CT scan. The anti-coagulation therapy was changed to an oral drug on the 7th day after hospitalization. The liver function tests normalized gradually. Although the rehabilitation for leg paralysis performed during hospitalization was continued after discharge from the hospital, the patient is unable to walk and uses a wheelchair. Hepatic arterial infusion chemotherapy is considered safe for blood and non-blood toxicity compared with systemic chemotherapy. However, there are also complications as in this case, where QOL is reduced remarkably, and caution is required.
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PMID:[A case of spinal infarction related to hepatic arterial infusion chemotherapy]. 1461 12

Folinic acid-modulated 5-FU regimens are standard elements in several chemotherapy combinations like FOLFIRI, FOLFOX or AIO-regimen in the palliative treatment of patients with gastrointestinal cancer. When the simultaneous mixed infusion of 5-FU and calcium-folinic acid (Leucovorin) was authorized by the BfArM in 2002, we introduced this application regimen in the treatment of our cancer patients. 19 patients (AIO-regimen [5], FOLFIRI [12] and FOLFOX [2]) received a simultaneously mixed infusion of calcium-folinic acid and 5-FU over 24 hours with a total of 110 applications. 5-FU doses varied between 2000 and 2600 mg/m2, calcium-folinic acid was given with 500 mg/m2, infusion rate was 10 ml/hour using a 24 h pump. Central venous catheters employed included single Barth-Port in 18 cases, 1 patient had a Viggon-Port. In 3 out of the 19 patients catheter occlusion was noticed after 8-10 weekly applications of the mixed infusion. Heparine and subsequently urokinase were not successful in reversing the obstruction. All three catheters had to be explanted. Catheter tips in all cases showed a yellow cristalline precipitation. The crystallographic analysis exhibited calcium carbonate (CaCO3) in its polymorphic form (calcite). Thus, we confirmed calcite formation causing catheter occlusion as a frequent complication during a continuous 24 h-infusion of mixed high dose 5-FU and calcium-folinic acid. This reaction could not be avoided by increasing infusion volume and the application flow rate. As a result of our findings, recommending using calcium-folinic acid mixed with 5-FU has been withdrawn in the meantime.
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PMID:[Occlusion of central venous port catheters after simultaneous 24 h infusions of 5-FU and calcium-folinic acid in patients with gastrointestinal cancer]. 1524 42