The efficacy of 2',2'-difluorodeoxycytidine (gemcitabine) combined with interferon in human renal cell carcinoma cell lines.

The present in vitro study on three human renal cell carcinoma (RCC) cell lines (A-498, ACHN, SN12C) evaluated the efficacy of 2',2'-difluorodeoxycytidine (dFdC, gemcitabine), vinblastine (VBL), rhu-interferon-alpha (IFN-alpha) and rhu-interferon-gamma (IFN-gamma) alone or in combinations. The cytotoxicity was measured by using the sulphorhodamine B colorimetric cytotoxicity assay. Analyses were made from cells being continuously long-term (4 weeks) or short-term (4 h) with IFN-alpha or IFN-gamma with regard to the cytotoxicity of the chemotherapeutic agents. dFdC was more cytotoxic against ACHN and A-498 cells compared to VBL. Pre-treatment with IFN-alpha enhanced growth inhibition caused by dFdC (4/4 cell lines) and VBL (2/3 cell lines), and was more effective than IFN-gamma. Pre-exposure with IFN-alpha sensitized SN12C and ACHN cells for dFdC. A-498 cells achieved a decreased sensitivity to dFdC and VBL after pre-exposure to IFN-gamma. The resistance of newly established dFdC-resistant SN12C cells (23-times) decreased when pre-treated with IFN-alpha. The data demonstrate efficacy of dFdC in human RCC at concentrations below clinically achievable doses. dFdC was more effective compared to VBL. Combined therapy preferentially with IFN-alpha increased cytotoxicity of dFdC in vitro. In vivo studies in nude mice xenografts are under investigation to support these observations.

Interferon-alpha and gemcitabine (2',2'-difluorodeoxycytidine) in adult and pediatric renal tumors.

2',2'-difluorodeoxycytidine (dFdC) is an active anticancer drug in different human malignancies. The present study aimed to evaluate if the activity of dFdC in renal tumors could be improved by interferon-alpha (IFN-alpha). The influence of IFN-alpha (4 h) on the cytotoxicity of dFdC was analyzed in vitro by a colorimetric assay. in vivo, nude mice with xenografts from human nephroblastoma (AC-KLxe-12) and renal cell cancer (ACHN, SN12C) were treated by dFdC +/- IFN-alpha. IFN-alpha alone resulted in no growth inhibition in vitro, but pretreatment with IFN-alpha sensitized SN12C and ACHN cells against dFdC. The additional treatment with IFN-alpha increased the CR rate of ACHN- and SN12C-mice (40%; 7%) compared to dFdC alone (20%; 0%). Xenografts from AC-KLxe-12 did all progress. In conclusion, IFN-alpha increased cytotoxicity of dFdC in vitro and tumor responses of renal cell cancer (RCC) in xenografts. Since therapy lacked activity in nephroblastoma, further studies should focus on RCC to compare the efficacy of dFdC and interferons with other types of biochemotherapy.

[Determination of the free thyroxine concentration (FT4) in serum using the FT4 fraction and total thyroxine concentration]. / Bestimmung der freien Thyroxinkonzentration (FT4) im Serum mit Hilfe der FT4-Fraktion und der Gesamtthyroxinkonzentration.

A new equilibrium assay for the determination of serum free thyroxine was evaluated in 514 patients. The assay comprises a two-vial-procedure to measure total thyroxine and free thyroxine fraction by use of monoclonal antibodies. Free thyroxine concentrations are calculated from fT4-fraction and total thyroxine concentration readings. In euthyroidism the average free thyroxine fraction (%fT4) was 0.011%, in hyperthyroidism this fraction was elevated, in hypothyroidism it was below normal. In patients with TBG anomalies, TBG values were inversely correlated with fT4 fraction readings. The "euthyroid reference range" of FT4 (SPAC ET) was between 0.70 to 1.78 ng/dl. This euthyroid range of FT4 was determined from TT4 concentrations measured by T4-RIA (SPAC T4 MONO) which were 30% above TT4 values measured by conventional T4-RIA (SPAC T4 POLY; polyclonal antibodies). However, a different euthyroid range of FT4 between 0.55 to 1.30 ng/dl was observed as well as by other investigators when conventional T4-RIA measurements were used for calculation of FT4 values. Our results indicate that calculated FT4 concentration values are highly dependent on the methods used for determination of total thyroxine concentrations. Precision and reproducibility of this two vial equilibrium assay did not meet the requirements mandatory for the application as a clinical routine diagnostic procedure, and its general use for this purpose can as yet not be recommended.

[Vitamin A and carotene in thyroid diseases]. / Vitamin A und Carotin bei Schilddrüsenkrankheiten.

From 190 goitrous patients (106 euthyroid, 53 hyperthyroid, 31 hypothyroid) serum levels of vitamin A and carotene were obtained. The serum levels of vitamin A were significantly decreased in both hyperthyroidism and hypothyroidism, the serum levels of carotene in hypothyroidism only. Remarkably, vitamin A levels almost never drop to subnormal values in hyperthyroidism. There is evidence, that a sufficient dietary protein supply enables the liver cell to produce enough amounts of retinol binding protein and prealbumin to overcome the increased clearance observed in hyperthyroid conditions.