Molekularnobiološke osobine oralnih skvamocelularnih karcinoma

Oral squamous cell carcinomas (OSCCs) are associated with poor prognosis, and despite advances in therapy approaches, no major improvement in survival has been achieved in the recent years. Efforts are now directed toward finding new biological markers that could predict tumor behavior more accurately. OSCCs, as the majority of malignant tumors, arise from progressive accumulation of genetic and epigenetic lesions, transforming normal cells into malignant. In this paper, an analysis of current studies directed to understanding the underlying mechanisms of OSCC pathogenesis was presented. The emphasis was put on mutational analysis of cancer genes, as well as on the role of viral infections and methylation processes in OSCC. Finally, an overview of studies that tried to determine the possibility for developing OSCC was given.Oralne skvamocelularne karcinome (OSCK) odlikuje uglavnom loša prognoza i, uprkos pomacima u terapijskim postupcima, poslednjih godina nije ostvaren napredak u preživljavanju osoba s ovim tumorom. Velike nade se polažu u molekularnu medicinu i pronalaženje novih bioloških markera pomoću kojih bi preciznije nego što to dopuštaju klinički i histopatološki parametri moglo da se predvidi ponašanje tumora. OSCK, kao i većina drugih malignih oboljenja, rezultat su postupne akumulacije raznovrsnih genetičkih i epigenetičkih promena u ćelijama, koje od normalnih postaju neoplastične. U ovom radu dat je presek nekih od pravaca istraživanja na polju molekularne biologije oralnih karcinoma, s osvrtom na studije koje se bave ispitivanjem somatskih mutacija u kancerskim genima, učešćem onkogenih virusa u patogenezi i značaju procesa metilacije za OSCK. Takođe su pomenute studije posvećene utvrđivanju eventualnog postojanja predispozicije za razvoj OSCK

Moleculobiological characteristics of oral squamous cell carcinomas

Oral squamous cell carcinomas (OSCCs) are associated with poor prognosis, and despite advances in therapy approaches, no major improvement in survival has been achieved in the recent years. Efforts are now directed toward finding new biological markers that could predict tumor behavior more accurately. OSCCs, as the majority of malignant tumors, arise from progressive accumulation of genetic and epigenetic lesions, transforming normal cells into malignant. In this paper, an analysis of current studies directed to understanding the underlying mechanisms of OSCC pathogenesis was presented. The emphasis was put on mutational analysis of cancer genes, as well as on the role of viral infections and methylation processes in OSCC. Finally, an overview of studies that tried to determine the possibility for developing OSCC was given.Oralne skvamocelularne karcinome (OSCK) odlikuje uglavnom loša prognoza i, uprkos pomacima u terapijskim postupcima, poslednjih godina nije ostvaren napredak u preživljavanju osoba s ovim tumorom. Velike nade se polažu u molekularnu medicinu i pronalaženje novih bioloških markera pomoću kojih bi preciznije nego što to dopuštaju klinički i histopatološki parametri moglo da se predvidi ponašanje tumora. OSCK, kao i većina drugih malignih oboljenja, rezultat su postupne akumulacije raznovrsnih genetičkih i epigenetičkih promena u ćelijama, koje od normalnih postaju neoplastične. U ovom radu dat je presek nekih od pravaca istraživanja na polju molekularne biologije oralnih karcinoma, s osvrtom na studije koje se bave ispitivanjem somatskih mutacija u kancerskim genima, učešćem onkogenih virusa u patogenezi i značaju procesa metilacije za OSCK. Takođe su pomenute studije posvećene utvrđivanju eventualnog postojanja predispozicije za razvoj OSCK.Projekat ministarstva br. 17507

Moleculobiological characteristics of oral squamous cell carcinomas

Oral squamous cell carcinomas (OSCCs) are associated with poor prognosis, and despite advances in therapy approaches, no major improvement in survival has been achieved in the recent years. Efforts are now directed toward finding new biological markers that could predict tumor behavior more accurately. OSCCs, as the majority of malignant tumors, arise from progressive accumulation of genetic and epigenetic lesions, transforming normal cells into malignant. In this paper, an analysis of current studies directed to understanding the underlying mechanisms of OSCC pathogenesis was presented. The emphasis was put on mutational analysis of cancer genes, as well as on the role of viral infections and methylation processes in OSCC. Finally, an overview of studies that tried to determine the possibility for developing OSCC was given.Oralne skvamocelularne karcinome (OSCK) odlikuje uglavnom loša prognoza i, uprkos pomacima u terapijskim postupcima, poslednjih godina nije ostvaren napredak u preživljavanju osoba s ovim tumorom. Velike nade se polažu u molekularnu medicinu i pronalaženje novih bioloških markera pomoću kojih bi preciznije nego što to dopuštaju klinički i histopatološki parametri moglo da se predvidi ponašanje tumora. OSCK, kao i većina drugih malignih oboljenja, rezultat su postupne akumulacije raznovrsnih genetičkih i epigenetičkih promena u ćelijama, koje od normalnih postaju neoplastične. U ovom radu dat je presek nekih od pravaca istraživanja na polju molekularne biologije oralnih karcinoma, s osvrtom na studije koje se bave ispitivanjem somatskih mutacija u kancerskim genima, učešćem onkogenih virusa u patogenezi i značaju procesa metilacije za OSCK. Takođe su pomenute studije posvećene utvrđivanju eventualnog postojanja predispozicije za razvoj OSCK.Projekat ministarstva br. 17507

Somatic Mutation and Polymorphism Analysis in Pleomorphic Adenomas of the Salivary Glands

Background: Genetic studies of salivary gland neoplasms were mainly focused on chromosomal changes, and some specific patterns of chromosome translocations have been described. However, molecular alterations, in particular the role of HER-2/H-ras/c-myc signalling cascade in pleomorphic adenoma pathogenesis (PA), are less well characterized. In addition, data on single nucleotide polymorphisms (SNPs) as potential susceptibility factors for PA development are also quite scarce. Methods: Mutational analyses were performed by means of real-time PCR (HER-2 and c-myc amplification analysis), PCR-SSCP and sequencing (H-ras point mutation detection). Polymorphisms analysis was performed by PCR-RFLP (survivin and MMP-9 genes). Results: Amplification of HER-2 and c-myc has been found in 13% and 9% of PA cases respectively. Point mutations in H-ras codons 12/13 have been detected in 17% of PAs. No correlation could be established between these alterations and clinical characteristics of PAs, whereas they might play a role in a subset of malignant salivary gland tumours. As for survivin -31 G/C polymorphism, C allele carriers had a 4-fold decrease of the risk of developing PA (p=0.05). Carriers of the variant allele T of the -1562C/T SNP in MMP-9 gene had a 4-fold increase of the risk of developing PA (p LT 0.001). Conclusions: A longer follow-up of PA patients harbouring mutations could uncover a prognostic role of HER-2 and c-myc amplification as predictors of adenoma transformation into carcinoma. Both survivin and MMP-9 promoter polymorphisms represent susceptibility factors for the development of PAs in the Serbian population

DNA Profiling of B Chromosomes from the Yellow-necked Mouse Apodemus flavicollis (Rodentia, Mammalia)

Using AP-PCR-based DNA profiling we examined some structural features of B chromosomes from yellow-necked mice Apodemus flavicollis. Mice harboring one, two, or three or lacking B chromosomes were examined. Chromosomal structure was scanned for variant bands by using a series of arbitrary primers and from these, informative bands were selected. The selection criteria used were the ability to differentiate between individuals of the species, to detect markers common for both A and B chromosomes, and, importantly, to differentiate between A- and B-chromosome sets. In addition to primers, profiling conditions were found to be critical for meeting the selection criteria. Primers and analysis conditions that demonstrated structural characteristics unique to the B-chromosome set are described. These characteristics included variant bands as qualitative parameters and altered electrophoretic band intensities as quantitative distinctions estimated by integration of densitometric profiles of electrophoretograms. B chromosome-specific molecular markers are easy to detect by AP-PCR-based DNA profiling in the presence of a full set of A chromosomes. Models for the origin of yellow-necked mouse B chromosomes are discussed in the context of presented data

Differential gene expression in yellow-necked mice Apodemus flavicollis (Rodentia, Mammalia) with and without B chromosomes

Most B chromosomes are heavily heterochromatic, promoting the general idea that they are genetically inert. The B chromosomes of Apodemus flavicollis are euchromatic and show a high degree of homology with the chromosomes. The euchromatic nature of chromosomes in A. flavicollis suggests that they may carry active genes and have transcriptional activity. We applied the differential display reverse transcription-polymerase chain reaction (DD RT-PCR) in order to analyze and compare gene expression in animals possessing chromosomes and animals without B chromosomes. After a second and third round of amplification, three cDNA fragments were differentially expressed in +B mice compared with 0B animals. These cDNAs were Chaperonin containing TCP-1, subunit 6b (zeta) (CCT6B), Fragile histidine triad gene (FHIT) and hypothetical gene XP transcript. The differential expression pattern was confirmed by Real Time RT-PCR. We suggest that altered expression of these important genes is due to the presence of B chromosomes. In elevating the expression of these genes, B chromosomes of A. flavicollis affect some of the crucial processes in the cell. The significance of these effects and the nature of B chromosomes of A. flavicollis are discussed in the context of the data presented

Differential gene expression in yellow-necked mice Apodemus flavicollis (Rodentia, Mammalia) with and without B chromosomes

Most B chromosomes are heavily heterochromatic, promoting the general idea that they are genetically inert. The B chromosomes of Apodemus flavicollis are euchromatic and show a high degree of homology with the chromosomes. The euchromatic nature of chromosomes in A. flavicollis suggests that they may carry active genes and have transcriptional activity. We applied the differential display reverse transcription-polymerase chain reaction (DD RT-PCR) in order to analyze and compare gene expression in animals possessing chromosomes and animals without B chromosomes. After a second and third round of amplification, three cDNA fragments were differentially expressed in +B mice compared with 0B animals. These cDNAs were Chaperonin containing TCP-1, subunit 6b (zeta) (CCT6B), Fragile histidine triad gene (FHIT) and hypothetical gene XP transcript. The differential expression pattern was confirmed by Real Time RT-PCR. We suggest that altered expression of these important genes is due to the presence of B chromosomes. In elevating the expression of these genes, B chromosomes of A. flavicollis affect some of the crucial processes in the cell. The significance of these effects and the nature of B chromosomes of A. flavicollis are discussed in the context of the data presented.nul

Le Grand écho du Nord de la France

30 septembre 19031903/09/30 (A85,N273).Appartient à l’ensemble documentaire : NordPdeC

Hematological toxicity associated with tiazofurin-influence on erythropoiesis

In this study hematological toxicity was analyzed after the single and repeated applications of tiazofurin (TZF). Cellularity of bone marrow, spleen and peripheral blood was examined, spanning the period of fifty days after the initial application. Analysis of hematological parameters was performed by slightly modified conventional techniques. The fraction of erythroid series was monitored during the experiment. Presented data describe kinetics of damage and recovery of hemopoietic tissue. Our results indicate that the effect of tiazofurin on cellularity of bone marrow and spleen and on erythropoiesis is reversible and dose dependent within tested dose range and therapeutic regimes. Twenty days after the application normal function of hemopoietic tissues was restored. This approach and results can be useful in defining the timing for sequencing and combination therapy with tiazofurin. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved

Identification of differentially expressed mRNA transcripts in drug-resistant versus parental human melanoma cell lines

Background: Malignant melanoma resistance to chemotherapy remains a major limitation to treatment. Our aim was to identify genes associated with drug resistance, in order to better understand the molecular events underlying the drug-resistant phenotype. Materials and Methods: A human melanoma cell line and its drug-resistant variants obtained by selection with MNNG or 6-thioguanine were used. Alterations in gene expression were characterized by differential display reverse transcription-polymerase chain reaction (DDRT-PCR). Prominent mRNA fragments present in selected variants and not in the parental cells were identified and characterized by cloning and sequencing. Differential expression was confirmed by real-time RT-PCR. Results: Three functionally distinct transcriptional products were demonstrated: the chaperonin subunit TCP 1-zeta-6A (CCT6A), the hyaluronan receptor CD44 and LPPR-2, the lipid phosphate phosphatase-related protein type-2. Conclusion: Genes with altered expression were identified in drug-resistant variants. The identified molecules may provide new insights into the molecular basis for melanoma resistance to chemotherapy