Clinical relevance of urokinase-type plasminogen activator, its receptor, and its inhibitor type 1 in endometrial cancer.

OBJECTIVE: Tumor invasion involves degradation of extracellular matrix. The urokinase plasminogen activation system participates in this process. Urokinase-type plasminogen activator (uPA), its receptor (uPAR), and its inhibitor, plasminogen activator inhibitor type 1 (PAI-1), are proposed to be prognostic factors in some cancers. There are conflicting data regarding the prognostic role of this system in endometrial cancer. METHODS: To determine the prognostic value of the urokinase plasminogen activation system, contents of uPA, uPAR, and PAI-1 were measured in extracts of endometrial cancer tissue using ELISAs. uPA, uPAR, and PAI-1 levels were determined in 91, 54, and 92 extracts, respectively, and correlated with tumor histology, stage, grade, lymph node involvement, prevalence of metastasis, and recurrence as well as with estrogen (ER), progesterone (PR), epidermal growth factor (EGFR) receptor and HER-2/neu contents. RESULTS: Patients with cancers exhibiting advanced stage, high grade, unfavorable tumor histology, nodal involvement, recurrence, and lower PR levels determined by ligand binding had significantly higher uPA content than others. PAI-1 was significantly elevated in patients with advanced stage, high-grade tumor, recurrence, decreased ER content, and lower PR levels determined by ligand binding. uPAR did not show any relation to any of clinical and laboratory parameters. Elevated expression of PAI-1 was associated with significantly shorter disease-free (P = 0.005) and overall (P = 0.0003) survival. Multivariate analysis revealed that PAI-1 was a predictor of survival although stage was the strongest independent factor. CONCLUSION: Elevated uPA and PAI-1 levels appear to correlate with unfavorable prognosis in endometrial cancer.

Clinical relevance of urokinase-type plasminogen activator, its receptor and inhibitor type 1 in ovarian cancer.

Urokinase-type plasminogen activator (uPA), its receptor (uPAR) and inhibitor, plasminogen activator-type 1 (PAI-1) are proposed to be of prognostic significance in some cancers. To determine the prognostic value of the urokinase plasminogen activation system in ovarian cancer, levels of uPA, uPAR, and PAI-1 were measured in extracts of ovarian cancer tissue using ELISA tests. uPA and PAI-1 were determined in 70 tumor extracts and uPAR in 43 extracts. Levels were correlated with age, tumor histology, stage, grade, lymph node and metastatic status, residual disease, risk of recurrence, epidermal growth factor receptor (EGFR) expression, cathepsin D (Cath-D), and c-erbB-2 levels. uPA and uPAR did not exhibit correlation with any of these parameters. However, patients with high grade tumor, recurrence, and lower EGFR and Cath-D had significantly higher PAI-1 levels compared to those of others (P < 0.05). Kaplan-Meier plots of survival were compared. uPA and uPAR were not related to disease-free or overall survival. Although low PAI-1 appeared to predict a longer overall survival, the difference was not statistically significant. Multivariate analysis revealed that PAI-1 was a predictor for overall survival although it was not as strong as stage. These results suggest that elevated PAI-1 seems to be correlated with an unfavorable prognosis in ovarian cancer.

Cardiac metastasis from carcinoma of the cervix: report of two cases.

BACKGROUND: The presence of cardiac metastasis from cervical carcinoma is extremely rare. The diagnosis is made almost exclusively postmortem. There are few cases of premortem diagnosis, and it is believed that when cardiac metastasis are found in vivo, the prognosis is extremely poor. Due to the rarity of this condition it is very difficult to standardize care for these patients. Considering the evidence provided by the cases in this report, it is possible that aggressive therapy may lengthen patients survival and quality of life. CASE: We present two cases of cervical carcinoma with metastasis to the heart. Both patients presented with symptomatology of cardiac tamponade. Both patients had invasion of the myocardium from presumed endomyocardial metastasis where the prognosis is even worse. We took an aggressive therapeutic approach to our patients and had excellent results in one. Our report includes the longest survival reported for a patient to date with premortem diagnosis of intramyocardial metastasis from cervical carcinoma. CONCLUSION: We concluded that the prognosis for cardiac metastasis from cervical carcinoma is extremely poor. The stage of the disease at initial presentation does not predict the future development of cardiac metastasis. Taking an aggressive therapeutic approach, including thoracentesis, chemotherapy, and radiation therapy to the heart, survival and quality of life can be improved.

Biopsy of the scalene fat pad in carcinoma of the cervix uteri metastatic to the periaortic lymph nodes.

Fifty-five patients with squamous cell carcinoma of the cervix uteri metastatic to high common iliac or periaortic lymph nodes underwent biopsy of the left scalene fat pad as part of a prospective clinical trial. Patients without metastasis to the scalene nodes were subsequently treated with extended field radiation therapy and were then eligible for a randomized trial of systemic chemotherapy. Only four patients were found to have micrometastases to the scalene fossa. This figure is appreciably lower than that reported in previous literature. While geographic failure continues to be a problem for this group of patients, routine use of left scalene fat pad biopsy before treatment is not recommended.

A randomized trial of high dose bolus metoclopramide versus low-dose continuous infusion metoclopramide in the prevention of cisplatin-induced emesis.

We compared the antiemetic efficacy of metoclopramide in a bolus low-dose infusion schedule to that of metoclopramide given in a conventional high-dose bolus schedule in a randomized crossover trial. Thirty-two treatment courses in 16 patients receiving cisplatin chemotherapy were evaluable. The metoclopramide regimen was either 2 mg/kg i.v. bolus, then 20 mg/h by infusion for 4 h, or 2 mg/kg i.v. bolus every 2 h for three doses. Dexamethasone 20 mg i.v. and diphenhydramine 50 mg i.v. were also given. Antiemetic efficacy was assessed by a questionnaire. There were no differences in antiemetic efficacy between the metoclopramide regimens. With either program, 75% of patients were emesis-free, 13% had mild symptoms, and 13% had moderate symptoms (greater than two emetic episodes). The infusion metoclopramide regimen was 30% less expensive than the bolus schedule in our pharmacy. Thus, we recommend low-dose metoclopramide infusion as a less expensive, equally effective alternative to high-dose bolus regimens for antiemetic treatment.

Human lymphoblastoid interferon in the treatment of advanced epithelial ovarian malignancies: a Gynecologic Oncology Group Study.

The purpose of this study was to evaluate the toxicity and antitumor activity of low doses of human lymphoblastoid interferon in 36 patients with measurable disease in whom higher priority treatment methods had failed. All but one had surgically confirmed advanced disease and had undergone initial treatment with a multiagent chemotherapeutic regimen in combination with cisplatin; four patients had also received radiation therapy. Their age range was 28 to 74 years. All had Gynecologic Oncology Group performance grade 2 or better (Karnofsky, 50% and above). Human lymphoblastoid interferon was administered at 5 megaunits/m2 intramuscularly, for 5 days per week (Monday through Friday) for 6 consecutive weeks. Patients who exhibited response or stable disease at 6 weeks were placed on a regimen of maintenance therapy at the same dose level for 2 days per week (Monday and Tuesday), for up to 12 months or until progression. Twenty-eight patients were evaluable for response: two with complete responses (7.1%), three with partial responses (10.8%), 14 with stable disease (50.0%), and nine with increasing disease (32.0%). Among the cumulative adverse effects, fatigue was most common, followed by moderate leukopenia and thrombocytopenia. Other observed adverse effects consisted of severe nephrotoxicity in two patients and myocardial infarction in one patient. It appears that therapy with human lymphoblastoid interferon may have cytostatic and possibly cytotoxic effects in this group of patients, with acceptable adverse reactions.