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Circulating CA 15-3 antigen levels were evaluated in patients with benign diseases and breast cancer patients with no clinical evidence of disease after surgery (NED). Patients with breast cancer NED were followed for tumor recurrence or death during a median of 12.9 months (range 1 to 25 months). CA 15-3 and carcinoembryonic antigen (CEA) were compared in the same breast cancer NED patient population. Elevated CA 15-3 levels (greater than 40 U/ml) were observed in 38 of 1220 patients with benign diseases (3.1%) and in 25 of 350 breast cancer NED patients (7.1%). Elevations of CEA (greater than 5 ng/ml) were observed in 23 patients with breast cancer NED (6.5%). Benign diseases that produced significant elevations of CA 15-3 were chronic hepatitis (42.9%), liver cirrhosis (13.3%), sarcoidosis (16.7%), tuberculosis (9.7%), and systemic lupus erythematosus (6.7%). In breast cancer NED, initial elevations of CA 15-3 were observed in 12 of the 297 patients that remained free of disease during the follow-up, and in 13 of the 40 patients that relapsed (4.0% vs. 32.5%, p less than 0.001). Initial CEA levels were elevated in 16 patients that remained NED and in 7 patients that relapsed (5.3% vs. 17.5%, p less than 0.001). Serial determinations of CA 15-3 in patients continuously NED showed persistent elevations in 4 cases. Three of these exhibited concomitant benign diseases. In relapsing patients, serial tumor marker determinations showed that elevations of CA 15-3 before any other clinical evidence of recurrence occurred significantly more frequently than elevations of CEA (45% vs. 25%, p less than 0.001). Overall, two or more serial elevated values of CA 15-3 were observed in 7 cases, and 6 of them (85%) eventually relapsed. Median survival from study entry was 18.3 months in patients with breast cancer NED that had initial elevated CA 15-3, compared to 25+ months in those with negative CA 15-3 (p less than 0.0001). We conclude that circulating levels of CA 15-3 antigen can be elevated in some patients with non-malignant diseases, and that serial determinations of CA 15-3 may be useful in the postsurgical follow-up of patients with breast cancer when specific types of benign diseases that may cause elevations of the antigen are excluded. Additionally, CA 15-3 is more sensitive than CEA in the early diagnosis of breast cancer recurrences, and the simultaneous assay of CEA does not add information to that of CA 15-3 alone.

In the attempt to prolong and stabilize the known antiaggregant activity of morpholinomethylurea (MMU) derivatives were prepared with carboxylic acids possessing antiaggregant, anti-inflammatory or hypolipemic activity. The results of the experiments showed the important anti-aggregant and hypolipemic activity of N-2-(p-chlorophenoxy)-isobutyryl-N'-morpholinomethylurea (plafibride, ITA 104). The results obtained seem to indicate that the activity of these new N-acyl-N'-MMU is due initially to the molecule per se although it cannot be totally ruled out that part of the pharmacodynamic effect of the MMU may depend on a prodrug-like behaviour.

A new antigen associated with breast cancer, CA 15.3, was determined in the serum of 690 breast cancer patients and controls. After establishing a maximum normal level of 40 U/ml in 140 healthy subjects and 350 patients with benign diseases, CA 15.3 was investigated in 190 breast cancer patients: CA 15.3 serum levels were statistically different in patients with no evidence of disease (20.6 +/- 11.2 U/ml), metastatic patients in response (33.5 +/- 24.0 U/ml) and metastatic patients not responding to therapy (stable disease, 98.9 +/- 50.4; progression, greater than 200). CA 15.3 serum levels seem to correlate with the extent of metastatic breast cancer. Further studies are needed to establish the role of this marker in the management of breast cancer patients.

Radioimmunoassay (TPA Prolifigen RIA) was used to determine the serum concentration of TPA in 333 patients with different kinds of non-tumoral diseases. Amounts higher than 90 U/l, that was taken as the upper normal limit, were observed in 40 per 100 of the cases, being higher than 200 U/l in 10 per 100. The frequency of abnormal amounts of TPA in non-tumoral diseases obliges to eliminate them before making a diagnosis of cancer.

The importance of the extent of metastatic disease in the circulating levels of CA 15-3 and carcinoembryonic antigens (CEA) was studied in 173 patients with advanced breast carcinoma. Estimates of the extent of metastatic disease were obtained by an objective arbitrary scale. Patients were observed clinically after serum samples were obtained, and survival was recorded. Elevated values of CA 15-3 (greater than 40 U/ml) were seen in 130 patients and CEA values (greater than 5 ng/ml) in 97 cases (75% versus 56%, P less than .0001). Elevated CA 15-3 values correlated with the estimated extent of metastatic disease (P less than .0001), number of metastases (P = .0006), and survival from study entry (P = .01). Elevated CEA values correlated with extent of disease (P less than .0001), but not with the number of metastases or with survival. No correlation was found between the elevated values of CA 15-3 or CEA and age, menopausal status, and initial tumor size or nodal status. The combination of the elevated values of CA 15-3 and CEA was more sensitive than CA 15-3 alone (P = .04), but there were no significant improvements when subgroups were considered. Significant differences, that depended on which specific organ was affected dominantly by metastases, were seen in the mean levels of CA 15-3 antigen. Similarly, patients with liver involvement had higher mean levels of CA 15-3 than those without hepatic metastases. A stepwise regression analysis of the dominant site of metastases, liver involvement, and estimated extent of disease showed that only the latter parameter retained a significant correlation with CA 15-3 antigen levels (P less than .0001). Median survival of patients who showed abnormal CA 15-3 levels was significantly shorter than that of patients with nonelevated CA 15-3 (10.1 versus 18.0 months, P = .04). This difference was not appreciated with CEA levels (10.2 versus 12.2 months, P = .4). We conclude that tumor marker levels in patients with advanced breast carcinoma correlate with the extent of metastatic disease. In addition, the CA 15-3 assay is more sensitive and correlates more accurately with the extent of disease than CEA. Finally, the observed CA 15-3 differences by organ involvement are related to the extent of disease variations. The objective evaluation of the extent of metastatic disease provides a new approach in the study and comparison of breast cancer-associated tumor markers.

In order to know the behavior of the tissue polypeptide antigen (TPA) as a tumor marker, the authors determine its amount in serum by means of radioimmunoassay (TPA Prolifigen RIA) in 441 patients having respiratory, digestive, urogenital, hematopoietic, mammary and other malignant tumors. The obtained results indicate that: TPA has no tumor specificity; however it increases in tumors without any other known tumor marker. TPA has no diagnostic value, but it is useful for the following up of digestive, mammary, respiratory, ovarian and testicular cancer; amounts of TPA comprised between 90 and 120 U/l are not specific and have no clinical significance; and it is very useful the simultaneous determination of CEA and TPA in the respiratory, digestive and mammary malignant neoplasms to help the clinical data in the evaluation of tumor mass (CEA) and tumor activity (TPA) without indication of tumor localization.

Oesophageal motility and lower oesophageal sphincter (LOS) competence were investigated in 13 patients with progressive systemic sclerosis (PSS) and in 16 patients with localized scleroderma (LS) by means of oesophageal manometry and 24-h pH monitoring of the distal oesophagus. Results were compared with those of a control group consisting of asymptomatic volunteers. Marked abnormalities in oesophageal motility and in acid exposure in the distal oesophagus were observed in PSS patients only. The mean resting pressure of the LOS was 10.1 +/- 1.5 mmHg in PSS, 21.4 +/- 1.1 mmHg in LS, and 23.8 +/- 2.0 mmHg in asymptomatic controls. Overall sphincter length was 24.1 +/- 3.4 mm in PSS, 31.1 +/- 1.6 mm in LS, and 39.0 +/- 2.0 mm in the control group. Spincter abdominal length was 12.1 +/- 2 mm, 15.4 +/- 1 mm, and 25.0 +/- 1 mm, respectively. The amplitude and duration of oesophageal waves were markedly reduced at 5, 10, and 15 cm above the LOS in PSS patients, with only the upper part of their gullet being spared. An abnormal acid exposure in the distal oesophagus was observed in 84.6% of PSS patients, whereas only 18.2% (2 of 11) of pH-tested LS patients had an abnormal 24-h pH test. These data show that a marked oesophageal involvement is present only in the systemic form of scleroderma. Oesophageal tests may be useful for a circumstantial diagnosis whenever the diagnosis of PSS is uncertain; however, their use does not seem to be justified as routine in patients with LS.

Creatine kinase B (CK-B) was evaluated as a tumor marker by radioimmunoassay determination of the isoenzyme in 518 persons (control group, malignant tumors, and several other diseases). Amounts higher than 8 ng/ml (upper normal limit) was observed in 12.6 per 100 of the digestive tumors, 6.1 per 100 of the mammary tumors, 37.7 per 100 of the respiratory tumors, and 22.2 per 100 of the prostatic tumors. A relation exists between CK-B and sigmoid flexure, liver, pancreas and esophagus tumors, between CK-B and acid phosphatase in prostate tumors, and between CK-B and evolution of digestive tumor. The determination of CK-B is useful in the case of tumors lacking known tumor markers, and also as a complementary sign in the diagnosis and evolution of sigmoid flexure and prostate neoplasms.

CA 15.3 is an antigen expressed by human breast carcinoma cells, and defined by two monoclonal antibodies, 115D8 and DF3. We used IRMA to determine the circulating serum levels of CA 15.3 in 1178 subjects with breast cancer, non-breast malignancies, benign diseases and controls. A threshold level of 40 U/ml was established with 140 healthy controls and 650 patients with benign diseases (respectively 0% subjects and 1.5% patients had abnormal antigen levels). Elevated CA 15.3 was found in 12 of 184 patients with malignancies different from breast cancer (6.5%), either epithelial carcinomas with distant metastases, mainly in the liver, or primary liver tumors. Breast cancer patients (n = 204) were analysed by prior therapy, UICC stage and WHO response to therapy. Eight of 134 (5.9%) patients with stage II or III breast cancer at presentation and no evidence of disease (NED) had elevated CA 15.3. All of 22 patients with stage IV breast cancer not responding to therapy (SD and PD) had antigen levels greater than 40 U/ml, as did 10 of 34 (29.4%) stage IV patients in objective response (CR + PR). Three of 14 pretreatment patients had abnormal marker levels, and they later proved to have distant metastases. Serum CA 15.3 values were statistically different (p less than 0.01) in NED (20.6 +/- 11.2 U/ml), CR + PR (33.5 +/- 24.0 U/ml), stable disease (98.8 +/- 50.4 U/ml) and progressive disease (greater than 200 U/ml) breast cancer patients. Our results suggest that circulating CA 15.3 antigen levels agree with the stage of breast cancer and with the response to therapy.