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Journal URL: http://www.spandidos-publications.com/or/ Melanomas are malignant tumours with high metastatic potential. The genetic alterations which lead to the transformation and progression of melanocytes to malignant melanoma remain obscure. Mutations in the ras gene family have been described, however their role in melanoma pathogenesis is still controversial. In this study we examined the incidence of H-, K- and N-ras mutations in 47 DNA samples isolated from paraffin-embedded 25 cutaneous and 22 uveal malignant melanoma tissues and a MeWo melanoma cell line using the Restriction Fragment Length Polymorphism (RFLP) analysis of PCR products. Only one mutation in codon 61 of the N-ras gene was found suggesting that the importance of ras mutations in melanoma tumourigenesis may be limited.

Journal URL: http://www.iiar-anticancer.org/main.php?id=2

Journal URL: http://www.sciencedirect.com/science/journal/00062953

Journal URL: http://www.spandidos-publications.com/or/ The binding activity of the AP-1 (FOS/JUN) complex to a negative regulatory element on the c-myc promoter was investigated in 7 tumour- versus normal lung specimens and it correlated with c-myc expression. AP-1 levels were found elevated in two samples representing stage I progression of the disease, while in three stage III tumour samples, the AP-1 binding activity was equal or slightly elevated compared with their normal adjacent tissue. Southern blot analysis revealed amplified c-myc in all three cases of stage III tumours. These results suggest that there is a negative correlation between FOS/JUN binding on c-myc promoter and the expression of c-myc during the progression of the disease, further supporting the fundamental role of AP-1 on c-myc regulation.

Journal URL: http://www.iiar-anticancer.org/main.php?id=2

Journal URL: http://www.iiar-anticancer.org/main.php?id=2

Journal URL: http://www.iiar-anticancer.org/main.php?id=2

Journal URL: http://www.nature.com/bjc/index.html

Journal URL: http://www.sciencedirect.com/science/journal/07350651

Journal URL: http://www.iiar-anticancer.org/main.php?id=2

Journal URL: http://www.anti-cancerdrugs.com/

Journal URL: http://www.spandidos-publications.com/or/ Infections caused by Human Cytomegalovirus (HCMV) and Epstein-Barr virus (EBV) are common in multiple transfused patients, such as patients with ßthalassaemia. The ability of the Polymerase Chain Reaction (PCR) to amplify HCMV and EBV DNA from blood and other samples makes this technique a valuable diagnostic tool for the detection of both viruses in the early stages of the infection. PCR was used for the amplification of a 435 bp region of the immediate early-1 (IE-1) gene of HCMV and a 375 bp sequence from the EcoRI Β fragment of EBV genome. Blood samples from 80 patients with ß-thalassaemia were examined. HCMV was found in 14 and EBV in 12 patients. The results obtained confirm the implications of HCMV and EBV in the diagnosis of viral infections in multiple transfused patients as well as the importance of PCR technique as a valuable diagnostic tool.

Journal URL: https://timssnet2.allenpress.com/ECOMRADRES/timssnet/login/tnt_login.cfm?redirect=E_PUBLISHER; http://www.jstor.org/action/showPublication?journalCode=radirese

Journal URL: http://www.iiar-anticancer.org/main.php?id=2 We have transfected recombinant plasmids carrying 5 ' c-myc sequences linked to the reporter gene chloramphenicol acetyl-transferase (cat) and to the selectable marker aminoglycoside phosphotransfarase (aph) into rat fibroblasts and obtained stable transfectants. The response to cis-platin of these cell lines was studied. At 5 X 10sM concentration cis-platin stimulates cat gene expression 9 and 11 fold respectively in cell lines containing constructs with c-myc promoter sequences truncated at -2319 and -350 relative to c-myc RNA start site PI. A third cell line expressing a myc/cat recombinant truncated at -290 shows no response to cis-platin, thus defining a cis-platin responsive element between coordinates -290 and -350 on the myc promoter region.

Journal URL: http://www.spandidos-publications.com/or/ Patients with ulcerative colitis (UC) and Crohn's disease have an increased risk for developing cancer of the colon. Mutations in the K-ras gene are relatively frequent in specimens from patients with sporadic colon cancer, but less frequent in cases of cancer complicating ulcerative colitis. In order to study the problem further we used the polymerase chain reaction (PCR) technique followed by a restriction fragment length polymorphism (RFLP) assay, to detect mutations at codon 12 of K-ras in biopsy specimens from patients with UC or Crohn's disease. Six among 27 patients (22.2%) with UC and 2 of the 19 patients (10.5%) with Crohn's disease examined, carried a mutation at codon 12 of K-ras. Our results indicate that mutations in K-ras may be a genetic marker that would reveal the predisposition to colon cancer among this group of patients.

Journal URL: http://www.sciencedirect.com/science/journal/03440338

Journal URL: http://www.sciencedirect.com/science/journal/10503862

Journal URL: Istituto nazionale per lo studio e lo cura dei tumori di Milano

P53 expression was assessed in 93 head and neck squamous cell carcinoma patients using CM-1, DO-7, and DO-1 antibodies. Sixty eight percent was found to have positive nuclear staining. The frequency of p53 mutations were investigated in 13 patients using single-stranded conformational polymorphism (SSCP) analysis of DNA fragments that had been amplified by the polymerase chain reaction (PCR). P53 gene mutations were analyzed by SSCP in exons 4 to 7 of 13 patients, and nine were found to have mutations in exon 4; two of these patients also had a mutation in exon 5. In the group of 93 patients, p53 overexpression was found to correlate with the patients' history of heavy smoking (p

A recombinant plasmid carrying the long terminal repeat (LTR) of the human immunodeficiency virus 1 (HIV-1) linked to the reporter chloramphenicol acetyl transferase (CAT) gene was stably introduced into human fibroblasts. The transfectant cells expressed CAT activity from the HIV LTR. The response to anti-neoplastic drugs, i.e. cisplatin, a platin derivative, and hexadecylphosphocholine, was studied. It was found that at 5 x 10(-6) M concentrations cisplatin stimulates by 2.2-fold the expression of CAT from the HIV LTR. Our results extend our observations on the effect of cisplatin on HIV LTR in rodent fibroblast cells and suggest caution against therapy including cisplatin in the treatment of AIDS patients.

Actinic keratosis (AK) is a well-established pre-cancerous skin lesion that has the potential to progress to squamous cell carcinoma (SCC). We investigated the involvement of the CDKN2A, CDKN2B and p53 genes in AK and in the progression of AK to SCC. Mutational analysis on exons 1a, 1b and 2 of the CDKN2A locus and exon I of the CDKN2B locus as well as allelic imbalance was performed in 26 AK specimens. Expression levels of the genes p14(ARF), p15(INK4b), p16(INK4a) and p53 were examined in 16 AKs and 12 SCCs by real-time RT-PCR. A previously described polymorphism of p16(INK4a) (Ala148Thr) was detected at an allelic frequency of 12%. Six samples carried novel mutations at codon 71 of the CDKN2A locus and one sample presented an additional mutation at codon 65. Two AK samples carried a not-previously described non-UV type missense mutation at codon 184 (Val184Glu) of exon 1b in the p14(ARF) gene. Regarding the CDKN2B locus a new mutation at codon 50 (Ala50Thr) and another at codon 24 (Arg24Arg), were detected. Microsatellite instability (MSI) was found in 15% of AKs in at least one marker, indicating that genetic instability has some implication in the development of AK. Down-regulation of p16(INK4a) and p53 mRNA levels was noted in SCC compared to AK. TSGs expression levels in sun-exposed morphologically normal-appearing skin, suggests that abnormal growth stimuli might exist in these tissues as well. Furthermore, we suggest a possible role of p15(INK4b), independently from the intracellular pathway mediated by p16(INK4a), and of p14(ARF) in AK development, as well as in the progression of AK to SCC. The deregulation of the expression profiles of the CDKN2A, CDKN2B and p53 genes may, independently of mutations and LOH at 9p21, play a significant role in AK and progression of AK to SCC. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

Background Factors that predict response and breakthrough phenomenon to lamivudine monotherapy in patients with HBeAg-negative chronic hepatitis B have not been well defined. Aim To determine pre-treatment and on treatment variables that predict initial response and breakthrough in patients with HBeAg-negative chronic hepatitis B receiving long-term lamivudine. Methods Seventy-nine patients, with chronic HBeAg-negative hepatitis B, who received lamivudine for a median of 31 months were included in the study. Results Initial virologic and biochemical response was observed in 73 (92%) and 70 (89%) patients, respectively, while 34 (47%) and 15 (21%) patients developed virological and biochemical breakthrough, respectively. High levels of necroinflammation in liver biopsy were associated with a higher probability of initial virological and biochemical response. Patients with pre-treatment serum hepatitis B virus DNA concentrations of more than 10(6) copies/mL were three times more likely to develop virologic breakthrough. Two patients died, one with baseline cirrhosis because of liver failure during biochemical breakthrough while the second death was liver and treatment unrelated. Conclusions In HBeAg-negative chronic hepatitis B, initial response to lamivudine therapy is associated with necroinflammation, while baseline serum hepatitis B virus DNA exceeding 10(6) copies/mL is a strong predictor for breakthrough because of drug-resistant mutations. Severe complications are uncommon and are associated with biochemical breakthrough and pre-existing cirrhosis.

Cytomegalovirus injection is common in kidney transplanted patients. Viremia is the only marker of active CMV infection, but the use of cell culture for the direct detection of the virus is time-consuming and not very sensitive, while the detection of CMV by measuring the titre of antibodies is difficult due to the immunosuppression these patients undergo. Thus the ability to amplify CMV DNA by the polymerase chain reaction from blood or urine samples of the patients becomes a valuable diagnostic tool for the detection of CMV in the early stages of the infection. Using a set of primers specific for the amplification of a 435 bp region of the IE-1 gene, we detected CMV DNA in blood leucocytes of a kidney transplanted patient who received the transplant from a CMV-seropositive donor, 45 days after the operation, while the antibody titre showed no evidence of active CMV infection.

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