Several Clinical Studies of Oncoscreen Ltd.

In addition to various commissioned molecular biological activities accompanying clinical studies and medical research projects, Oncoscreen has to date in the field of molecular laboratory diagnostics, initiated three clinical studies and analysed retrospectively a past study on the basis of paraffin preserved tissue samples. Analyses of both mutations and gene expressions were performed.

Retrospective Analysis of paraffin preserved Tumour samples (FOGT1/2) Retrospective Analysis of paraffin preserved Tumour samples (adjCCA-01) Retrospective Study of DPD Molecular diagnostics Prospective Study of DPD Molecular diagnostics Study of the Correlation between the Status of the Promotor of the Thymidylate Synthase (TS) and the Response of the Tumor to 5-Fluorouracil Treatment Study of the Correlation of the Expression of the Topoisomerase I and the Response of the Tumor to Irinotecan Treatment

Oncoscreen can assist you to achieve professional results from molecular biological investigations in the framework of clinical studies. Further details can be found on the page Molecular Biological Assistance with your Clinical Studies.

Retrospective Analysis of Studies of the German Research Group Oncology of Gastrointestinal Tumours (Forschungsgruppe Onkologie gastrointestinaler Tumore, FOGT)

Oncoscreen has retrospectively analysed the adjuvant studies of colonic carcinoma (FOGT1) and rectal carcinoma. (FOGT2). In this connection paraffin preparations from 471 tumour samples were processed, and 331 tumours (70%) could be analysed molecular biologically with respect to the strength of the gene expression of Thymidylate-Synthase (TS), Dihydropyrimidine-Dehydrogenase (DPD) and Thymidine-Phosphorylase (TP). This was the first comprehensive investigation into the significance of these markers in the adjuvant treatment of colorectal tumours. The results were published:
Kornmann et al.: Association of time to recurrence with thymidylate synthase and dihydropyrimidine dehydrogenase mRNA expression in stage II and III colorectal cancer. J Gastrointest Surg. 2002 May-Jun;6(3):331-7.
Kornmann et al.: Thymidylate synthase and dihydropyrimidine dehydrogenase mRNA expression levels: predictors for survival in colorectal cancer patients receiving adjuvant 5-fluorouracil. Clin Cancer Res. 2003 Sep 15;9(11):4116-24.

A prospective follow-up study (FOGT4-Study) will be microbiologically accompanied by Oncoscreen under commission of the Research Group for the Oncology of Gastrointestinal Tumours.

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Retrospective Analysis of paraffin preserved samples from the study adjCCA-01 (adjuvant Chemotherapy of colon carcinoma)

Oncoscreen investigated the expression of Thymidylate-Synthase (TS), Dihydropyrimidine-Dehydrogenase (DPD) and Thymidine-Phosphorylase (TP) in 124 paraffin preserved primary tumour samples. The investigation yielded that to a large extent the relapse frequency correlates positively with lower medians of TS gene expression values (p = 0.02), according to the multivariance analysis. The results were published as a poster (Nehls et al.: Intratumoral Thymidylate Synthase Gen Expression and Clinical Outcome subsequent to an Adjuvant Therapy with 5-Fluorouracil as a Bolus Application in the Case of Colon Carcinoma in Stage III) at the annual conference 2001, of the German Society for Digestive and Metabolic Illnesses (Deutschen Gesellschaft fuer Verdauungs- und Stoffwechselkrankheiten, DGVS)

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Side Effects of 5-Fluorouracil/DPD-Exon-14-Skipping-Mutation

A study by Oncoscreen and the Clinic for Internal Medicine II of the Friedrich Schiller University Jena, involving nearly 900 volunteers and cancer patients, which was retrospectively performed to investigate the prevalence of the Exon-14-Skipping-Mutation in the DPD gene, has recently been successfully completed. In this course of this undertaking, both the statistical investigation of the prevalence of this mutation (1%) and the determination of relevance of this mutation in connection with the occurrence of life threatening side effects of 5-Fluorouracil, were successfully concluded and documented. The results of this study were published (Raida M, Schwabe W, Hausler P, Van Kuilenburg AB, Van Gennip AH, Behnke D, Hoffken K.: Prevalence of a common point mutation in the dihydropyrimidine dehydrogenase (DPD) gene within the 5'-splice donor site of intron 14 in patients with severe 5-fluorouracil (5-FU)- related toxicity compared with controls. Clin. Cancer Res. 2001 Sep;7(9):2832-9.)

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Prospective follow-up DPD Molecular Diagnostics study is in clinical analyses

A prospective follow-up study involving 1455 patients was initiated in 2001 and was finished in July 2003. The goal of this study was to elucidate the quantitative relation between the genotype and phenotype of carriers of the DPD Exon 14 Skipping mutation. Oncoscreen identified within this group of patients 15 carriers of this specific DPD mutation which confirmed the earlier data of the prevalence of this mutation. Carrier of the Exon 14 Skipping mutation showed a significant slower turn over rate of the DPD catabolism and a distinct higher disposition to severe side effects after 5-Fluorouracil treatment. A publication is in preparation.

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Study of the Correlation between the Status of the Promotor of the Thymidylate Synthase (TS) and the Response of the Tumor to 5-Fluorouracil Treatment

The amount of TS enzyme is depended upon the activity of the TS gene which itself is depended on the promotor status of the TS gene. Two specific alleles of the TS promotor are known one of which decreases the activity of the TS gene. Several clinical studies showed that the tumors of patients with the decreased TS activity responded better to the 5-FU drug. Currently, Oncoscreen and the German Research Group Oncology of Gastrointestinal Tumours (FOGT) investigate this correlation within a clinical study.

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Study of the Correlation of the Expression of the Topoisomerase I and the Response of the Tumor to Irinotecan Treatment

The chemotherapeutic drug Irinotecan (CPT-11, Campto) inhibits the Topoisomerase I (TOPO I). In consequence, rapidly growing cells like tumor cells are not able to finish the DNA replication and, therefore, die. There are numerous scientific reports which show that a high expression of the TOPO I gene correlates with a higher response to TOPO I. Currently, Oncoscreen and the German Research Group Oncology of Gastrointestinal Tumours (FOGT) investigate this correlation within a clinical study.

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