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D A Spandidos

Publications and source records attributed to D A Spandidos.

At least 37 records · Page 2Linked to original sources
PubMed2001

Microsatellite DNA assays reveal an allelic imbalance in p16(Ink4), GALT, p53, and APOA2 loci in patients with endometriosis.

OBJECTIVE: To detect allelic imbalance on specific genetic loci occurring in endometriosis. DESIGN: Microsatellite analysis. SETTING: Paraffin-embedded tissues histologically confirmed as endometriotic or normal endometrium. PATIENT(S): Premenopausal women undergoing laparoscopy for suspected endometriosis. INTERVENTION(S): Laparoscopic excision of specimens. MAIN OUTCOME MEASURE(S): Allelic imbalance and alterations of intensity of microsatellite alleles. RESULT(S): Five of 17 microsatellite DNA markers (29.4%) showed allelic imbalance. Eight samples (36.4%) showed allelic imbalance in at least one locus. Loci 9p21, 1q21, and 17p13.1 exhibited imbalance in 27.3%, 4.5%, and 4.5%, respectively. A 3-fold increase of the fractional allelic loss was observed from disease stage II to III and IV, whereas only 1.3-fold was found between patients of 41-50 and 20-40 years. CONCLUSION(S): We found that loss of heterozygosity on p16(Ink4), GALT, and p53, as well as on APOA2, a region frequently lost in ovarian cancer, occurs in endometriosis, even in stage II of the disease. The occurrence of such genomic alterations may represent important events in the development of endometriosis. The 9p21 locus may contain a gene associated with the pathogenesis of the disease, and therefore its loss may be a prognostic marker of the disease.

Adult↗
PubMed2001

Low-penetrance genes are associated with increased susceptibility to endometriosis.

OBJECTIVE: To investigate whether genetic polymorphisms of CYP1A1, GSTM1, and GSTT1 are associated with endometriosis. DESIGN: Genetic polymorphism analysis. SETTING: University department. PATIENT(S): A family with four women in two generations who had endometriosis and one member with suspected endometriosis in the third generation were compared with a group of fertile women. INTERVENTION(S): Laparoscopic examination. MAIN OUTCOME MEASURE(S): Blood specimens were obtained from fertile females and available affected female family members. Multiplex polymerase chain reaction (PCR) and restriction fragment length polymorphism PCR was done to determine each participant's genotype. RESULT(S): All affected family members had genotype CYP1A1 wt/m1 and GSTM1 null deletion. The frequency of this genotype in 54 fertile women was 13%. A 17-year-old family member with suspected endometriosis had the same genotype. One affected member was also a carrier of a GSTT1 null deletion. This combination was not found in any of the fertile participants. The most frequent genotypes in the sample were CYP1A1 wt/wt, with GSTM1 null deletion and at least one functional allele of GSTT1, and CYP1A1 wt/wt, with at least one functional allele of GSTM1 and GSTT1 (33% and 31%, respectively). CONCLUSION(S): The combination of CYP1A1 m1 polymorphism and GSTM1 null deletion is closely associated with penetration of the endometriosis phenotype, whereas GSTT1 null deletion may add to the penetration of this trait.

Adolescent↗
PubMed2001

p53 Codon 72 polymorphism is linked to the development and not the progression of benign and malignant laryngeal tumours.

The p53 codon 72 polymorphism, resulting in either an arginine or a proline residue has been proposed to affect the susceptibility of p53 protein to human papilloma virus (HPV) E6-mediated degradation in vitro. However, there are controversial results from several clinical studies in various human tumours. The purpose of our study was to investigate the significance of this p53 genotype with respect to the risk of neoplasia development in Greek patients with benign and malignant laryngeal tumours. Furthermore, we searched for an association between p53 alleles and the presence of HPV in the same series of samples. We found a significant statistical association in the distribution of p53 genotypes between laryngeal lesions and normal samples (P<0.001). Allelic analysis of the patients with both benign and malignant tumours revealed a striking over-representation of the homozygous p53Arg allele compared to normal population (P<0.0003). HPV was detected in only 3 laryngeal samples (1 benign and 2 malignant tumours). This is the first study correlating the p53 codon 72 polymorphism in laryngeal tumours. Our results provide evidence that this p53 polymorphism may be implicated at the early stages of the disease and concerns predisposition to premalignant laryngeal lesions rather than to progression from benign tumour toward malignancy. Moreover, we demonstrate that the p53Arg homozygous genotype affects the predisposition for laryngeal tumours while the heterozygous status does not. The low incidence of HPV infection suggests that it is not a major oncogenic factor in the development of laryngeal tumours but may have synergistic action with specific genotypes of p53 gene.

Carcinoma, Squamous Cell↗
PubMed2001

Detection of herpes simplex virus and human papilloma virus in ophthalmic pterygium.

PURPOSE: To evaluate the presence of herpes simplex virus (HSV) and human papilloma virus (HPV) in pterygia and phenotypically normal conjunctiva and the possible relation between viral presence and clinical information. METHODS: Fifty pterygia and respective conjunctival specimens were obtained. A personal and family history was recorded for each patient. HSV and HPV detection and typing were accomplished by polymerase chain reaction amplification of viral sequences. Results were statistically analyzed. RESULTS: HSV (type 1) was detected in 11 (22%), HPV (type 18) in 12 (24%), and both HSV-1 and HPV-18 in 3 (6%) of pterygia. No conjunctival specimen displayed HSV, whereas HPV was detected in four (8%). Postoperative recurrence and history of conjunctivitis were significantly more common in patients with simultaneous detection of HSV and HPV. CONCLUSION: The fact that HSV was not detected in conjunctival specimens implies a more specific correlation with pterygium, as compared with HPV. The detection of potentially oncogenic viruses, such as HSV and HPV, supports the concept that pterygium can be considered a neoplastic condition. The correlation of postoperative recurrence and a history of conjunctivitis with the simultaneous detection of HPV and HSV, implies a possible viral cooperation affecting the clinical profile of pterygium.

Adult↗
PubMed2001

Genetic detection of bladder cancer by microsatellite analysis of p16, RB1 and p53 tumor suppressor genes.

PURPOSE: We investigated the incidence of genetic alterations in urine specimens from patients with bladder cancer. MATERIALS AND METHODS: A total of 28 cytological urine specimens were assessed for microsatellite alternations, and 15 microsatellite markers were located on p53, RB1 and p16 regions. In 15 patients DNA from tumor specimens was also available. RESULTS: Loss of heterozygosity was detected in 26 of 28 patients (93%) in at least 1 microsatellite marker. Allelic losses were found in 18 patients (64%) for the p16 locus, in 8 (29%) for the RB1 locus and in 17 (61%) for the p53 region. In contrast, no microsatellite alterations were found in the normal group without evidence of bladder cancer. In 11 cases genetic alterations in the cytological urine specimens were not detectable in the corresponding tumor specimen, suggesting heterogeneity of bladder cancer. CONCLUSIONS: The detection of loss of heterozygosity in cytological urine specimens may be a prognostic indicator of early detection of bladder cancer. Our results suggest that microsatellite analysis of urine specimens represents a novel, potentially useful, noninvasive clinical tool to detect bladder cancer.

Aged↗
PubMed2001

Genetic polymorphisms and transcriptional pattern analysis of CYP1A1, AhR, GSTM1, GSTP1 and GSTT1 genes in breast cancer.

In order to detect the contribution of cytochrome P450 1A1 (CYP1A1), aryl hydrocarbon receptor (AhR), glutathione S-transferases M1 (GSTM1), P1 (GSTP1), and T1 (GSTT1) genes in breast cancer, genetic analysis was performed, as well as transcriptional analysis in sporadic primary tumours and corresponding adjacent normal tissues from the same patient. CYP1A1 3'-untranslated region (3'-UTR) termed as m1 (MspI) polymorphism and the null(-) deletions of both GSTM1 and GSTT1 genes were examined in genomic DNA from blood samples of 207 female breast cancer patients and 171 age and sex matched controls. The frequencies of the m1 genotype of the CYP1A1 gene in cases and controls were 0.13 and 0.15, while the frequencies of homozygotes with GSTM1(-) were 0.52, in each, and for homozygotes with GSTT1(-) were 0.14 and 0.10, respectively. Statistical analysis of these genotypes in combinations did not reveal any significant difference between the breast cancer population and the control group. Expression of mRNA levels of CYP1A1, GSTM1, GSTP1, GSTT1 and AhR genes in 31 breast cancer patients, revealed inter-individual variation in an independent manner to patient age, genotype, or tumour stage. Eighty-seven percent of the tumour specimens tested were deregulated, compared to their normal counterparts, in at least one locus. Up-regulation of CYP1A1 was observed only when one of the GSTM1 or GSTP1 was down-regulated while the other remained constant. Genotyping analysis did not show any correlation to breast cancer risk. However, RT-PCR analysis provided evidence that CYP1A1, AhR, GSTM1, GSTP1 and GSTT1 genes are frequently deregulated in breast cancer and could be used as molecular biomarkers for better clinical management of such patients, with respect to chemotherapy.

Adult↗
PubMed2001

Extended genetic alterations in a patient with pulmonary sarcoidosis, a benign disease.

BACKGROUND: Genetic alterations at the microsatellite level have been detected in various human malignant tissues, but have also been found in chronically inflamed tissues. Sarcoidosis is a benign disease of unknown etiology characterized by chronic inflammation, which may be associated with an increased incidence of developing malignancy. METHODS: We examined the microsatellite alterations in a sputum cytological specimen of a patient with sarcoidosis. The DNA electrophoretic pattern of sputum was compared with that of the peripheral blood. Thirty-two microsatellite markers located at chromosomes 2p, 3p, 8p, 9p, 9q, 17p, 17q were used to reveal genetic alterations. RESULTS: Loss of heterozygosity (LOH) was detected in eleven markers in loci 2p, 9p, 9q and 17q. LOH was observed in all four markers spanning the chromosomal arm 17q11.2-q21, suggesting a potential chromosomal deletion. CONCLUSION: The observation of LOH in all four markers spanning the chromosomal arm 17q11.2-q21 may suggest a potential for malignancy development in this patient, or may be linked to the aetiopathogenesis of sarcoidosis. Further microsatellite fine mapping and clinical follow up of this patient are needed to clarify this.

Adult↗
PubMed2000

Human papillomavirus infection of non-melanoma skin cancers in immunocompetent hosts.

Human papilloma viruses (HPVs) consist of more than 70 different types and are known to be associated with numerous malignant tumors, including carcinomas of the mucosal and cutaneous epithelium. Non-melanoma skin carcinoma (NMSC) is the most frequently occurring malignancy worldwide in the Caucasian population. Most studies examining the involvement of papillomaviruses in the development of cutaneous carcinomas have been performed on lesions from patients with epidermodysplasia verruciformis or from immunosuppressed patients. Our specimens were obtained from 108 immunocompetent patients with benign and malignant skin lesions, and HPVs were detected in 27%. HPV 8 and HPV 18 were the most frequent types (62 and 48%, respectively). Our results suggest that HPVs, particularly the oncogenic potential of certain types such as HPV 8, 18, and 5 could contribute to the development of NMSCs.

Basal Cell Carcinoma↗
PubMed2000

RNA polymerase III transcription factor TFIIIC2 is overexpressed in ovarian tumors.

Most transformed cells display abnormally high levels of RNA polymerase (pol) III transcripts. Although the full significance of this is unclear, it may be fundamental because healthy cells use two key tumor suppressors to restrain pol III activity. We present the first evidence that a pol III transcription factor is overexpressed in tumors. This factor, TFIIIC2, is a histone acetyltransferase that is required for synthesis of most pol III products, including tRNA and 5S rRNA. TFIIIC2 is a complex of five polypeptides, and mRNAs encoding each of these subunits are overexpressed in human ovarian carcinomas; this may explain the elevated TFIIIC2 activity that is found consistently in the tumors. Deregulation in these cancers is unlikely to be a secondary response to rapid proliferation, because there is little or no change in TFIIIC2 mRNA levels when actively cycling cells are compared with growth-arrested cells in culture. Using purified factors, we show that raising the level of TFIIIC2 is sufficient to stimulate pol III transcription in ovarian cell extracts. The data suggest that overexpression of TFIIIC2 contributes to the abnormal abundance of pol III transcripts in ovarian tumors.

Acetyltransferases↗
PubMed2000

Allelic loss at the BRCA1, BRCA2 and TP53 loci in human sporadic breast carcinoma.

Abnormalities in several genes are known to confer susceptibility to breast cancer. In the present study, we investigated the incidence of allelic imbalance at the BRCA1, BRCA2 and TP53 loci, in 82 sporadic breast carcinomas using a bank of highly polymorphic microsatellite markers located at the BRCA1, BRCA2 and TP53 regions. Genetic alterations were observed in 58/82 (71%) cases in at least one microsatellite marker, at one of the three regions. Twenty-seven out of 82 (33%) cases exhibited loss of heterozygosity (LOH) at BRCA1 locus while in 20/82 (34%) cases LOH was observed for the BRCA2 region. Allelic deletions were detected in 28/82 (34%) cases for the TP53 locus. Our results suggest that allelic deletion at the above genetic loci play an important role to the development of sporadic breast tumours.

BRCA2 Protein↗
PubMed2000

P53 codon 72 polymorphism as a risk factor in the development of HPV-associated cervical cancer.

Human papilloma virus (HPV) has been implicated in cervical carcinoma, and the p53 gene is polymorphic at amino acid 72 of the protein that it encodes. The association between p53 polymorphisms and risk for HPV-associated cervical cancer has been examined, but the results have been conflicting. It has been reported that patients with the arginine form have a higher risk of developing cervical cancer than those with the proline form. The purpose of this study was to examine whether p53 Arg at the polymorphic position 72 could represent a risk factor for women with high-risk HPV-associated premalignant and malignant cervical lesions. The study was carried out on 60 smears from patients with high-risk HPV-related cervical lesions. Also, 74 HPV-negative normal smears and 61 normal blood samples were used as controls. HPV-18 was the most frequent type. There was a difference in the distribution of p53 genotypes between high-risk HPV-cervical lesions and the normal samples. The allele frequency of p53 Arg/Arg was much higher than the normal samples (46.5% versus 20.5% in HPV-negative normal smears and 20% in blood samples). Based on the findings of this study, it is suggested that p53 Arg homozygosity could possibly represent a potential risk factor for the tumorigenesis of the cervix. Statistically significant correlation was not observed between the presence of Arg/Pro homozygosity or Arg/Pro heterozygosity and HPV typing.

Codon↗
PubMed2000

p53 codon 72 polymorphism as a risk factor in the development of breast cancer.

The p53 gene is polymorphic at amino acid 72 of the protein that it encodes. It has been reported that patients with the arginine form have a higher risk of developing other forms of cancer than those with the proline form. The purpose of this study was to examine whether p53 Arg at the polymorphic position 72 could represent a risk factor for women with breast lesions. The study population included 56 biopsies from patients with breast lesions. Also, 61 normal blood samples were used as controls. There was a difference in the distribution of p53 genotypes between breast cancer lesions and the normal samples. The allele frequency of p53 Arg/Arg was much higher than that of the normal samples (61% versus 20%). Based on the findings of this study, it is suggested that p53 Arg homozygosity could represent a risk factor for the tumorigenesis of the breast.

Adult↗
PubMed2000

Loss of heterozygosity in DNA mismatch repair genes in human atherosclerotic plaques.

To detect the incidence of loss of heterozygosity (LOH) in DNA mismatch repair genes (MMR) occurring in atherosclerosis, fifty human autopsy cases of atherosclerosis were examined for LOH using 19 microsatellite markers, in three single and four tetraplex microsatellite assays. The markers used are located on or close to MMR genes. Fourteen specimens (28%) showed allelic imbalance in at least one locus. Loci hMSH2 (2p22.3-p16.1), hPMS1 (2q24.1-q32.1), and hMLH1 (3p21.32-p21.1) exhibited LOH (10, 10, and 12% respectively). We found that loss of heterozygosity on hMSH2, hPMS1, and hMLH1, occurs in atherosclerosis. The occurrence of such genomic alterations may represent important events in the development of atherosclerosis.

Aged↗
PubMed2000

High frequency of loss of heterozygosity on chromosome region 9p21-p22 but lack of p16INK4a/p19ARF mutations in greek patients with basal cell carcinoma of the skin.

Basal cell carcinoma of the skin is the most common neoplasia in humans. Previous studies have shown the existence of allelic imbalance (loss of heterozygosity and microsatellite instability) in BCC on several human chromosomes. Chromosome region 9p21-p22 harbors the CDKN2a/p16INK4a, p19ARF, and p15INK4b tumor suppressor genes. To determine the contribution of these genes to the development of basal cell carcinomas we looked for evidence of allelic imbalance in 67 sporadic basal cell carcinoma specimens from Greek patients and screened 28 of them presenting loss of heterozygosity at 9p21-p22 for germline mutations in p16INK4a and p19ARF genes. Chromosome regions 17q21 and 17p13 were also screened for allelic imbalance in all the 67 basal cell carcinoma specimens. Overall, 69% (46 of 67) of the specimens displayed loss of heterozygosity in at least one microsatellite marker, whereas only six of the 67 (9%) exhibited microsatellite instability. For the 9p21-p22 locus the overall frequency of loss of heterozygosity reached 55% (37 of 67) and is the highest reported. The overall frequency of loss of heterozygosity for the 17q21 locus is 34% (22 of 64) and for the 17p13 locus is 11% (seven of 65). Two of the 28 loss of heterozygosity positive cases were heterozygous for a previously described polymorphism, Ala148Thr, in exon 2 of the CDKN2a gene. This is the first demonstration of polymorphism in the CDKN2a gene in human basal cell carcinomas. No sequence variation in exon 1beta of the p19ARF gene was found. Our results provide evidence of a significantly high occurrence of loss of heterozygosity for the 9p21-p22 locus; however, lack of p16INK4a/p19ARF mutation suggests that these genes seem not to be implicated by mutational inactivation in the development of basal cell carcinoma. Other(s), yet unidentified, tumor suppressor gene(s) located in this locus may be related to this specific type of skin cancer.

Adult↗
PubMed2000

Allelic loss in chromosomal region 1q21-23 in breast cancer is associated with peritumoral angiolymphatic invasion and extensive intraductal component.

AIMS: Breast cancer is the most frequent cancer in the female population and the involvement of chromosomal alterations is often implicated in the development of cancer. The aim of our study was to assess loss of heterozygosity (LOH) in chromosome 1 in relation to clinical and pathological parameters. METHODS: Tumours, corresponding normal tissues and peripheral blood samples from 50 women with operable breast cancer, were analysed by polymerase chain reaction (PCR) at 16 polymorphic DNA markers, on both the long and short arm of chromosome 1. RESULTS: There was a significant correlation between chromosomal region 1q21-23 and the presence of extensive intraductal component (EIC) and peritumoral angiolymphatic (PALI) invasion, both independent markers of local recurrence. CONCLUSIONS: Allelic loss in region 1q21-23 may be a valuable prognostic biological marker for the detection of local relapse in breast cancer, in combination with other histological and clinical parameters.

Alleles↗
PubMed2000

Molecular basis of gynecological cancer.

Alterations in the cellular genome affecting the expression or function of genes controlling cell growth and differentiation are considered to be the main cause of cancer. Genes that cause cancer are of two distinct types: oncogenes and onco-suppressor genes. The normal proto-oncogene can be converted into an active oncogene by deletion or point mutation in its coding sequence, gene amplification, and by specific chromosome rearrangements. Mutations and abnormal expression in ras, myc, c-erbB-2, and other oncogenes have been reported in several types of gynecological cancer. Onco-suppressor genes are involved in gynecological cancer, their functions are localized in different phases of the cell cycle. Structural changes and deletions of these genes can cause cancer. Mutations in the p53, BRCA1, DCC, and PTEN genes have been reported in gynecological cancers such as ovarian, cervical, and endometrial cancer. Human papillomaviruses are of major interest because specific types (HPV-16, -18, and several others) have been identified as causative agents in at least 90% of cancers of the cervix. In this study we summarize the available information regarding the implication of specific oncogenes, onco-suppressor genes, and HPV in the development of female genital malignancies.

Female↗
PubMed2000

Frequent genetic alterations at the microsatellite level in cytologic sputum samples of patients with idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a disease of unknown etiology associated with DNA damage and malignancy. Bronchogenic carcinoma is the cause of death in 10% to 13% of IPF patients. Microsatellite instability (MSI) and loss of heterozygosity (LOH) are frequently detected in cancers. If these genetic alterations could be observed in IPF, they might explain the higher relative risk of lung cancer in this disease. We investigated the incidence of MSI and LOH in sputum cytologic specimens from 26 IPF patients and 26 healthy, matched subjects, using 10 highly polymorphic microsatellite markers. The electrophoretic pattern of each specimen was compared with that of corresponding peripheral blood. Thirteen (50%) patients showed genetic alterations, consisting either of MSI or LOH. Five (19%) patients exhibited MSI and 10 (39%) exhibited LOH in at least one microsatellite marker. Three (12%) patients showed LOH in more than one marker. None of the healthy subjects exhibited genetic alterations in the studied markers. No correlation was found between the detected genetic alterations and age, disease duration, blood gases, or spirometric parameters of the patients. Our findings suggest that the genetic alterations that we studied are frequent in IPF, are apparently unrelated to the severity of the disease, and may be related to tumorigenesis.

Aged↗