[Report of the National Oncology Research and Developement Consortium, 2003].
Consorcial projects focused on 5 cancer types, breast-, colorectal-, head and neck- and pediatric cancers, and malignant melanoma. Breast cancer studies revealed unique splicing mechanisms concerning BRCA1. In sporadic breast cancers the involvement of DNA-repair genes was proved to be dependent on the histological type. Bone-metastatic tumors have been characterized by decreased NM23 and increased c-met and p53 expressions. C-erbB2 genotype of the primary tumor was not maintained frequently in bone metastases. Application of DNA-microarray and quantitative PCR technologies improved the prediction of therapeutic sensitivity of breast cancers. Colorectal cancer studies revealed regional inhomogenities (clusters) in various geographical regions of Hungary, which were distinct in the case of colonic and rectal cancers. To increase the sensitivity of fecal blood test of colorectal cancer screening, a new double-antibody test was developed and tested in a large cohort of patients. Genetic analysis revealed that hypermethylation is a significant factor in microsatellite instability which, and plays a role in silencing of APC and E-cadherin genes as well. The Hungarian pattern of TS polymorphism was also determined and was correlated not only with the efficacy of 5-FU treatment but with the progression of the disease as well. Population-based studies have been carried out in head and neck cancer patients (HNC) and smokers as well to reveal the genetic background of increasing tumor incidence. These studies revealed polymorphism in XRCC1/3 methylation enzyme gene which has preventive role. Other studies found frequent local immunosuppression in HNC patients. Studies indicated that the success of irradiation in this cancer type is dependent on the anti-vascular effects. Pediatric cancer studies determined the parameters of neuroblastoma screening based on VMA measurements. New splice variants of the WT1 gene involved in the monitoring of MRD of ALL patients was also described this year. We also obtained positive experimental data for the retinoic acid therapy of ALL. Melanoma studies extensively used DNA-microarray technology which identified 4 melanoma-specific and 2 melanoma progression-specific genes. In experimental human melanoma xenograft models we have identified 3 anti-metastatic agents: low molecular weight heparin, 2-methoxyestradiol and erythropoietin-alpha, where the later was characterized by specific effects on tumor vasculature.
Tímár
József
J
Nemzeti Onkológiai Kutatás-fejlesztési Konzorcium, Budapest, Hungary. jtimar@oncol.hu
D000077584:2-Methoxyestradiol; D000328:Adult; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000032:analysis; D035843:Biomedical Research; D001859:Bone Neoplasms / Q000453:epidemiology / Q000235:genetics / Q000556:secondary; D001943:Breast Neoplasms / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics / Q000628:therapy; D002648:Child; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics / Q000628:therapy; D019175:DNA Methylation; D004195:Disease Models, Animal; D018450:Disease Progression; D000068817:Epoetin Alfa; D004921:Erythropoietin / Q000494:pharmacology; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D005819:Genetic Markers; D006258:Head and Neck Neoplasms / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics / Q000628:therapy; D006495:Heparin, Low-Molecular-Weight / Q000494:pharmacology; D006801:Humans; D006814:Hungary / Q000453:epidemiology; D015994:Incidence; D008297:Male; D008545:Melanoma / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics / Q000628:therapy; D018895:Microsatellite Repeats; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011237:Predictive Value of Tests; D011994:Recombinant Proteins; D014183:Transplantation, Heterologous
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D005819:Genetic Markers; D006495:Heparin, Low-Molecular-Weight; D011994:Recombinant Proteins; D004921:Erythropoietin; D004958:Estradiol; D000068817:Epoetin Alfa; D000077584:2-Methoxyestradiol