Proliferation-dependent induction of apoptosis by the retinoid CD437 in p53-mutated keratinocytes

6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-Naphthalene carboxylic acid (CD437) is a synthetic retinoid with strong apoptogenic properties in various neoplastic cell lines. CD437 was shown to induce apoptosis in malignant human keratinocytes but not in normal keratinocytes. We demonstrate that CD437 is also capable of inducing apoptosis in the non-tumorigenic keratinocyte cell line HaCaT that carries UV-type mutations on both alleles of the p53 gene. The concentration-dependent induction of apoptosis was restricted to proliferative HaCaT cells, whereas no effect was seen in differentiating post-mitotic cells. The apoptotic elimination of the proliferative cells was accompanied by rapid upregulation of c- jun, downregulation of c- fos, and activation of the AP-1 complex, which normally only occur during the differentiation process of post-mitotic keratinocytes. Pharmacological impairment of this precocious AP-1 activation reduced the rate of apoptosis induced by CD437. The potent, selective, and p53-independent apoptosis-inducing efficacy of CD437 is of utmost importance for the prophylaxis and treatment of skin cancer caused by mutational inactivation of the p53 gene.     

Multicenter evaluation of a chromogenic substrate method for photometric determination of prothrombin time

A multicenter study of a chromogenic substrate method for photometric determination of prothrombin time was conducted in order to evaluate its clinical application. Seven laboratories participated in the study using a total of 742 plasma samples from 417 patients on oral anticoagulant therapy, 261 healthy subjects and 64 patients with different diseases especially of the liver as well as 30 patients with hereditary deficiency of coagulation factors II, V, VII, X. The chromogenic PT method was compared to a standardized coagulometric PT assay which uses the same sensitive human placenta thromboplastin calibrated against international reference preparations. A high correlation of the prothrombin ratio values of the chromogenic and the coagulometric assay was obtained in 402 plasma samples (r = 0.940; y = 1.02x - 0.1). The study showed that the chromogenic PT reagent is sensitive to deficiency of the coagulation factors of the extrinsic pathway but not affected by heparin up to 1 IU/ml because of the heparin antagonist added. The precision (coefficient of variation) of the photometric method ranged between 0.6 and 3% (intraassay CV) and between 1.4 and 5.8 (interassay CV). The International Sensitivity Index (ISI) obtained for the used lot was 1.09. The therapeutical range in percentage activity for patients in a stable phase of an anticoagulant therapy was found to be from 15 to 27 percent of normal. The results of the clinical evaluation proved the good comparability of the new chromogenic PT test with coagulometric methods, its high factor sensitivity, good reproducibility and easy performance.     

Leukoplakia of the prepuce with epidermolytic hyperkeratosis: a case report

A leukoplakic lesion of the prepuce is described with the histologic and ultrastructural features of epidermolytic hyperkeratosis. The lesion represents most likely a variant of epidermolytic leukoplakia recently observed in the vermilion border of the lip.     

Gene Expression-Based Approaches in Differentiation of Metastases and Second Primary Tumour

A 64-year-old male patient was diagnosed with 3 consecutive non-small cell lung carcinomas (NSCLC). In the current study, we applied whole-genome gene expression analysis to control, primary and locally recurrent cancer, and supposed metastasis samples of a single patient. According to our knowledge, there are no published papers describing the gene expression profiles of a single patient''s squamous cell lung cancers. As the histology and differentiation grade of the primary cancer and the supposed metastasis differed minimally, but local recurrence was poorly differentiated, molecular profiling of the samples was carried out in order to confirm or reject the hypothesis of second primary cancer. Principal component analysis of the gene expression data revealed distinction of the local recurrence. Gene ontology analysis showed no molecular characteristics of metastasis in the supposed metastasis. Gene expression analysis is valuable and can be supportive in decision-making of diagnostically complicated cancer cases.Key Words: Local recurrence, Non-small cell lung cancer, NSCLC, Metastasis, Gene expression profile