Evaluation of response to chemotherapy in patients affected with non-small cell lung cancer by means of three tumour markers elaborated by discriminant analysis.

Chemotherapy is the most effective treatment for inoperable patients (70%) affected with non-small cell lung cancer (NSCLC). The early detection of tumour progression is mandative in order to promptly shift these patients towards salvage or supportive therapy. The present authors investigated the clinical value of a panel of tumour markers, elaborated by means of discriminant analysis, as a follow-up indicator for the detection of tumour progression. The serum levels of tissue polypeptide antigen (TPA), CYFRA-21.1, neuron-specific enolase (NSE) and carcino-embryonic antigen (CEA) were determined before chemotherapy and after three cycles of treatment. Discriminant analysis generated a formula (canonic variable) which correctly classified the 87.8% of the 74 subjects (86.1% of the 36 progressive diseases and 89.5% of 38 non-progressive diseases). This approach produces an algorithm able to calculate a progression score in NSCLC patients which can be helpful for following-up care and therapy control of these patients.

Validation of an algorithm able to differentiate small-cell lung cancer (SCLC) from non-small-cell lung cancer (NSCLC) patients by means of a tumour marker panel: analysis of the errors.

By means of a mathematical score previously generated by discriminant analysis on 90 lung cancer patients, a new and larger group of 261 subjects [209 with non-small-cell lung cancer (NSCLC) and 52 with small-cell lung cancer (SCLC)] was analysed to confirm the ability of the method to distinguish between these two types of cancers. The score, which included the serum neuron-specific enolase (NSE) and CYFRA-21.1 levels, permitted correct classification of 93% of the patients. When the misclassifications were analysed in detail, the most frequent errors were associated with limited disease SCLC with low NSE levels and with advanced NSCLC with high NSE levels. This demonstrates the importance of the marker in correctly categorizing patients.

Effect of extracellular sodium on thyroid hormone uptake by mouse thymocytes.

In mouse thymocytes, a stereospecific saturable energy-dependent and ouabain-inhibitable system facilitates T3, but not T4, entry. We studied here the effect of sodium depletion on cellular uptake of thyroid hormones by mouse thymocytes. Time-course experiments indicated that extracellular sodium depletion reduced [125I]T3 uptake at each time studied. At equilibrium, the removal of extracellular sodium and its substitution with isoosmotic choline decreased saturable [125I]T3 uptake by 60 +/- 10%; this effect was dose dependent. The substitution of sodium with lithium, instead of choline, had no effect on the uptake process. [125I]T4 uptake was lower than that of [125I]T3 and not affected by sodium depletion. The half-maximal effect of sodium deprivation on [125I]T3 uptake was reached at an extracellular sodium concentration of about 40 mM. The variation of external pH influenced T3 accumulation by thymocytes. [125I]T3 progressively decreased from acid to alkaline pH under normal and sodium-depleted conditions; however, the sodium-dependent fraction was more than doubled at physiological pH compared to that at more acidic and more alkaline pH. The sodium ionophore monensin decreased T3 uptake by 51% at a concentration of 20 microM. These results indicated the existence of a sodium-related mechanism of T3 uptake into mouse thymocytes that does not operate for T4 uptake.