J. J. Fennelly

Urokinase-plasminogen activator, a marker for aggressive breast carcinomas. Preliminary report

Plasminogen activator is a serine protease which exists in two forms, known as tissue‐type plasminogen activator and urokinase‐type plasminogen activator. Here, we show that urokinase‐type plasminogen activator activity in primary breast carcinomas correlates with both size of tumor and number of axillary nodes with metastases. Patients with primary carcinomas containing high levels of urokinase‐type plasminogen activator activity had a significantly shorter disease‐free interval than patients with low levels of activity. It is concluded that urokinase‐plasminogen activator may be a new prognostic marker in breast cancer.

Serum sialic acid and CEA concentrations in human breast cancer.

The concentration of bound sialic acid in the sera of 56 normal subjects and 65 subjects with breast cancer was measured, in order to determine (1) whether serum sialic acid concentrations are raised in breast cancer and (2) whether the concentration of sialic acid in serum reflects tumour stage. The amount of sialic acid in serum was compared to serum carcinoembryonic antigen (CEA) values. Urinary hydroxyproline and serum alkaline phosphatase concentrations were used as indicators of bone and liver involvement. Erythrocyte sedimentation rate (ESR) was also measured. Significantly elevated serum sialic acid concentrations were found in breast cancer, and showed correlation with tumour stage. Serum sialic acid values did not correlate with CEA values. The results suggest that measurement of serum sialic acid concentrations may be of adjunctive value in assessing tumour stage.

Urokinase Plasminogen Activator as a Prognostic Marker in Different Subgroups of Patients with Breast Cancer

Background. Urokinase plasminogen activator (uPA) is a serine protease involved in cancer invasion and metastasis. Previously, uPA was shown to be an independent prognostic marker in breast cancer. The aim of this study were to evaluate uPA as a prognostic marker in different subgroups of patients with breast cancer.

Homocystinuria: II. Subnormal serum folate levels, increased folate clearance and effects of folic acid therapy

Abstract In eight homocystinuric children, low fasting serum folate levels were found. Folic acid absorption, intravenous clearance studies and formiminoglutamic acid excretion after l-histidine loading were the parameters investigated. Increased utilization of folic acid was noted and its implications are discussed. Oral folic acid therapy in two patients brought about a decrease in the urinary excretion of homocystine and an increase in methionine excretion. The usefulness of pharmacologic doses of folic acid as an adjunct to dietary treatment of this condition is advanced as an important measure.

An evaluation of predisposing factors for testis cancer in Ireland.

All testis cancer in Ireland (1980-1985) was analysed (n = 240). Incidence was highest in young adults (5.8/10(5)/year in those aged 25-34 years) with a moderate level in the elderly (1.8/10(5)/year in those over 75 years). Associations elsewhere with maldescent and social class were confirmed but cryptorchidism (12%) was more common than expected. Significant infertility was not identified. Associations with urban domicile (77%, p = 0.001), mental handicap (2.8%, p less than 0.05), recent vasectomy (1.2%, p = 0.009) and certain occupations were observed.

Prospective randomized double-blind trial of nabilone versus domperidone in the treatment of cytotoxic-induced emesis

SummaryA prospective randomized double-blind trial comparing the butyrophenone analogue domperidone (D) and the synthetic cannabinoid nabilone (N) in the treatment of cytotoxic-induced emesis was conducted in 38 patients receiving highly emetogenic chemotherapy regimens (70% containing cisplatin). Patients received 20 mg D or 1 mg N the night before chemotherapy and 8-hourly on each chemotherapy day for two consecutive cycles of treatment.Three of 19 patients randomized to N completed only one cycle because of disease progression (2) or subjectively adverse effects (1). Four of 19 patients completed only one cycle of D because of lack of efficacy (3) or chemotherapy toxicity (1). In all, 32 cycles of N and 33 cycles of D were evaluable for efficacy. The mean number of vomiting episodes in cycle 1 was 4.76 for N and 12.95 for D (P<0.02). The corresponding values for cycle 2 were 4.27 and 7.69 (P>0.10), and for cycles 1 and 2 combined, 4.53 for N and 10.81 for D (P<0.01). Nausea and food intake scores did not differ significantly, although there was a trend towards less nausea and an increased food intake with N. Subjectively adverse effects were more frequent with N and included drowsiness, dizziness, dry mouth, and postural hypotension. N is superior to D for the control of cytotoxic-induced emesis.

Urokinase plasminogen activator as a predictor of aggressive disease in breast cancer.

Urokinase plasminogen activator (uPA) is a multifunctional protein involved in both extracellular proteolysis and signal transduction. uPA usually mediates its actions while attached to a membrane-bound receptor, termed uPAR. In this study, uPA and its receptor were measured at both protein and mRNA levels in breast cancer. At both levels, concentrations of uPA were significantly correlated with those for uPAR. uPA levels also correlated significantly with cathepsin B and cathepsin D but not with cathepsin L, MMP-8 or MMP-9 levels. Irrespective of the cut-off point used (e.g., median, tertile or quartile values), uPA was a significant prognostic marker for breast cancer.

Influence of prior orchiopexy on stage and prognosis of testicular cancer.

Thirty-four cryptorchid testis cancer cases were studied, of whom 9 patients had prior orchiopexy at the time of cancer diagnosis. Disease stage in this group was: stage I = 4, stage II = 1 and stages III and IV = 4 cases. Seventy-eight percent of these cases (n = 7) had non-seminomas; 4 of these patients died. In the uncorrected cryptorchidism group (n = 25), disease stage was: stage I = 12, stage II = 9 and stages III and IV = 4 cases. Of these cases, 64% (n = 16) had seminomas and 6 patients died. Orchiopexy marginally reduced the symptomatic interval for subsequent cancer and probably decreased the risk of seminoma development. Orchiopexy did not lead to a more favourable disease presentation or prognosis because of the adverse bias of advanced-stage non-seminomas in this group.

The clinical value of CEA and CA 15-3 in breast cancer management.

The value of tumour-associated antigens CEA and CA 15-3 was studied in patients with breast cancer over a 4-year period. A total of 252 patients with primary or recurrent disease had available and corresponding CEA and CA 15-3 values at diagnosis and during follow-up and were studied in detail. Preoperative and three-monthly serial postoperative levels were measured in each patient. Ten of 11 patients presenting with primary and concurrent metastatic disease had elevated CA 15-3 levels (> 25 I.U./ml) as compared to 6 with CEA (> 5 ng/ml). Fourty-seven patients developed locoregional recurrence of which 15 had concurrent metastatic disease. CA 15-3 was elevated in 14 cases while CEA in 11. Of 32 patients with locoregional recurrence alone, 18 later developed metastatic disease at a mean follow-up time of 17.5 months. There was a significant correlation between CA 15-3 value at locoregional recurrence and time to subsequent metastasis (r = 0. -0.57, P = 0.0133). CEA was elevated in 64%, CA 15-3 in 87% and either marker in 94% of 87 patients diagnosed with metastatic disease. Of 53 patients with serial markers and metastatic disease, 72% (38/53) had rising CA 15-3 levels prior to diagnosis with a mean lead time of 9.9 months. Use of CEA in conjunction improved lead time detection to 83%. This study demonstrates that CA 15-3 is superior to CEA at detecting metastatic disease at initial presentation and during follow-up. Use of CEA in conjunction with CA 15-3 improves the detection of systemic disease.

ε-Amino-Caproic Acid in the Management of Acute Promyelocytic Leukaemia

In three cases of acute promyelocytic leukaemia remission was induced with cytosine arabinoside, daunarubicin and vincristine. The coagulopathy was controlled by EACA without resorting to the use of h