Circadian and seasonal variations of hematopoiesis in cord blood.

Cord blood hematopoietic progenitors undergo circadian and seasonal variations. The lowest values are obtained between 4:00 and 12:00, as well as between May and August. This represents the first observation of such rhythms before birth.

Monoclonal immunoradiometric assay and polyclonal radioimmunoassay compared for measuring neuron-specific enolase in patients with lung cancer.

Neuron-specific enolase (NSE) is the most sensitive and specific tumor marker for small-cell lung cancer (SCLC). We evaluated a new monoclonal IRMA (Sangtec) for NSE and compared it with a polyclonal RIA (Pharmacia) in patients with SCLC or other lung cancers (NSCLC). We measured NSE concentrations in 100 healthy subjects (NI group), 100 patients with benign pulmonary diseases (BPD group), and 194 patients with advanced lung cancer (97 SCLC and 97 NSCLC). Intra- and interassay CVs were less than 7% for both assays, and dose-dilution curves paralleled their respective standard curves. Values measured by both assays were highly correlated in all groups. NSE concentrations were significantly (P less than 0.001) lower by IRMA than by RIA in NI and BPD groups. The upper 95th percentile values for NSE in the NI group were 11.7 micrograms/L in the RIA and 9.2 micrograms/L in the IRMA. In NSCLC, the values were significantly (P less than 0.05) lower by IRMA but the percentage of subjects with increased values was higher (vs the NI group, 31% for RIA and 44% for IRMA, P less than 0.005). Diagnostic sensitivity for SCLC was improved with IRMA: 83% of values with RIA and 93% with IRMA were increased above the NI group values (P less than 0.005); the corresponding values for SCLC vs BPD were 81% and 89% (P less than 0.05). NSE values measured in 39 patients with SCLC after chemotherapy were more often increased and were significantly higher with the IRMA than with the RIA (P less than 0.005).

Evaluation of squamous cell carcinoma antigen as a new marker for lung cancer.

Carcinoembryonic antigen (CEA) is the only tumor marker of proven, although limited, value for the management of patients with non-small cell lung cancer (NSCLC). The authors have prospectively assessed the potential value of a new tumor marker, squamous cell carcinoma antigen (SCC Ag), in a large series of patients with advanced lung cancer (LC). Squamous cell carcinoma antigen and CEA levels were measured in 382 healthy persons (N1 group), 90 patients with benign pulmonary diseases, and 291 patients with LC (129 with SCLC and 162 with NSCLC, including 96 with squamous LC). Carcinoembryonic antigen levels were higher in smokers than in nonsmokers, but smoking habits did not influence the serum concentrations of SCC Ag. Elevated values (above the 95th percentiles of N1, i.e., 7.5 ng/ml for CEA and 3.0 ng/ml for SCC Ag) were observed in 11.1% of patients with benign pulmonary diseases for both markers. Carcinoembryonic antigen was more sensitive than SCC Ag, even for squamous LC (56% versus 35% of elevated values, P less than 0.01). The specificity toward squamous LC was better, however, for SCC Ag, for which levels were elevated in only 8.5% of SCLC and in 18% of other forms of NSCLC, compared with 49% and 55%, respectively, for CEA. Moreover, measurement of SCC Ag and CEA levels did not give redundant information: thus, in squamous LC and SCC Ag level was elevated in 32% of the patients with a normal CEA level, increasing from 57% to 71% the proportion of patients with at least one elevated marker. Lastly, elevation of CEA or SCC Ag levels was an adverse prognostic factor in squamous LC (P = 0.05 for CEA; P = 0.07 for SCC Ag). In conclusion, SCC Ag appears to be worthwhile of further investigation in squamous LC. The authors found that this new marker provided additional information on CEA and that it was more specific for squamous LC than CEA.

Pharmacokinetics of repeated i.v. bolus administration of high doses of r-met-Hu interleukin-2 in advanced cancer patients.

We studied the pharmacokinetics of recombinant methionyl human interleukin-2 alanine (r-met-Hu IL-2 [ala 125]) given at high doses by i.v. bolus according to Rosenberg's initial schedule in seven patients with advanced cancer. Serum concentrations of IL-2 were measured by radio-immunoassay. The drug followed second-order kinetics. During the administration of repeated high doses of IL-2, we noted a progressive increase in the volume of distribution (from 5,984 +/- 1,850 to 9,084 +/- 4,345 ml) and a progressive decrease in the AUC (from 32,643 +/- 3,817 to 22,397 +/- 511 IU min ml-1) and beta-half-life (from 61 +/- 14 to 48 +/- 6 min); the peak serum IL-2 concentrations also decreased significantly. We attribute these findings to an expansion of the extracellular fluid space and an increase in the number of IL-2 target cells during the treatment.

A preliminary evaluation of calcitonin and PDN-21 as tumor markers for lung cancer. EORTC Lung Cancer Working Party.

Immunoreactive calcitonin (iCT) can be ectopically secreted by lung cancer cells and has been proposed as a tumor marker for bronchial neoplasms. Since PDN-21 (katacalcin or the carboxyl-terminal flanking peptide of the calcitonin gene) and CT are cosecreted in normal subjects and in patients with medullary thyroid carcinoma (MTC), we sought to determine the potential utility of PDN-21 as a tumor marker for lung cancer. We measured carcinoembryonic antigen (CEA), neurone-specific enolase (NSE), iCT, and PDN-21 in 119 to 378 healthy subjects, 88 to 91 patients with benign pulmonary disease, and 249 patients with advanced lung cancer (108 small cell lung cancers and 141 other forms). Tumor marker specificity was satisfactory: the percentage of increased values (greater than the 95th percentile of normal subjects) in patients with benign pulmonary diseases varied from 9% (NSE, PDN-21) to 12% (CEA). PDN-21 was a more sensitive marker for lung cancer than iCT: the percentage of increased values was 44% for PDN-21 versus 19% for iCT, and 51% versus 23% for the subgroup of patients with small cell lung cancer (SCLC). PDN-21 concentrations were increased in 69 (34%) of 202 patients with a normal iCT level, whereas iCT concentrations were increased in only six (4%) of 139 patients with a normal PDN-21 level. However, markedly elevated concentrations of the two markers generally occurred in the same patients and the correlation between the two markers was significant (rs = 0.60; P less than 0.01). PDN-21 provided complementary information to that from the classical markers NSE and CEA.(ABSTRACT TRUNCATED AT 250 WORDS)