phosphorus-radioisotopes and Uterine-Cervical-Neoplasms

Topics: Cervix Uteri; DNA, Viral; Female; Humans; Nucleic Acid Hybridization; Papillomaviridae; Phosphorus Radioisotopes; Tumor Virus Infections; Uterine Cervical Diseases; Uterine Cervical Neoplasms; Vaginal Smears

The profiling of differentially expressed genes from primary tumor samples using cDNA expression array can reveal new tumor markers as well as target genes for therapeutic intervention. Using cDNA expression array technology, we produced an expression profile of genes that are associated with human cervical cancer. Hybridization of the cDNA blotting membrane (588 genes on a single membrane) was performed with 32P-labeled cDNA probes synthesized from RNA isolated from either normal cervix or cervical cancer. Parallel analyses of the hybridized signals enabled us to profile genes that were differentially expressed in cervical cancer. In each experiment, the extent of hybridization of each gene was evaluated by comparison with the most abundant mRNAs in the human cervix. These include myc proto-oncogene, 40S ribosomal protein S19, heat shock proteins, leukosialin S (CD43), integrin alphaL (CD11A), calgranulin (A), and CDK4 inhibitor (p16ink4). No detectable changes were observed in the expression levels of these genes. Several mRNAs, such as those encoding guanine nucleotide-binding protein Gs (alpha subunit), leukocyte adhesion protein (LFA1-beta), nuclear factor NF45, homeobox protein Hox-A1, and beta-catenin were detected in increased levels in cervical cancer. Genes that showed decreased expression in cervical cancer tissue were a group of apoptosis-related proteins, cell adhesion molecules, nuclear transcription factors, and a homeobox protein (Hox7). For example, the expression levels of Smad1 and Hox7 were consistently decreased in all tumor tissues tested. Northern analysis of Smad1 and Hox7 RNA in primary cervical tumor tissues and cervical carcinoma cell lines indicated that, in general, the mRNA levels of these genes were decreased in human cervical cancer. The precise relationship between the altered expression of these genes and cervical tumorigenesis is a matter of further investigation.

Topics: Disease Progression; DNA, Complementary; DNA, Neoplasm; Female; Gene Expression; Humans; Oligonucleotide Array Sequence Analysis; Phosphorus Radioisotopes; Proto-Oncogene Mas; RNA, Neoplasm; Uterine Cervical Neoplasms

Numerous epidemiological studies have shown that there is an association between smoking and cervical cancer. However, the essential evidence to show whether this relationship is casual or causal is lacking. The demonstration of DNA modification by tobacco components in the cervical epithelium would provide biochemical evidence to support a causal role. In this study, DNA from 39 cervical biopsies was analysed for the presence of DNA adducts using the 32P-postlabeling technique. A questionnaire on smoking habit and a urinary cotinine assay were used to identify smokers and nonsmokers. DNA samples from smokers [identified from questionnaire] were found to have significantly higher adduct levels than nonsmokers (Mann-Whitney one-tailed U-test, 95% CI > 0.339, P = 0.024). Exclusion of the women whose urinary cotinine levels did not confirm their self-reported smoking status (smoker or nonsmoker) increased this significance (95% CI > 0.508, P = 0.01). Women who had abnormal cervical smears had significantly higher DNA adduct levels than those with normal smears (95% CI > 0.439, P = 0.015). Monitoring of women with high DNA adduct levels may be a way of identifying women at risk of cervical cancer. These findings demonstrate that tobacco smoking by women leads to elevated levels of DNA adducts in cervical epithelium and provides the biochemical evidence to support the concept that smoking is a cause of cervical cancer.

Topics: Adult; Aged; DNA; Epithelium; Female; Humans; Middle Aged; Phosphorus Radioisotopes; Reference Values; Smoking; Uterine Cervical Neoplasms; Vaginal Smears

32P-Postlabelling was used to measure DNA adducts in the human cervix. Adduct levels were compared with patient smoking histories and contraceptive use. DNA adducts were found in 43 out of 58 samples. The number of adducts ranged from 0.2 to 59.5 adducts/10(8) nucleotides, though no significant difference was found to exist between the number of DNA adducts detected and the smoking history of each patient. In contrast, a significant difference at the 1% probability level was found between the adduct levels obtained from the cervical DNA of smokers who had used oral contraceptives and smokers who did not. Autoradiograms revealed a variety of adduct patterns. Some were found to have a diagonal zone of radioactivity which migrated from the origin of the TLC plate. Other autoradiograms revealed the presence of additional adduct spots located in the upper regions of the TLC plate, whereas others revealed the presence of these adduct spots alone. The origin of the adduct spots located in the upper regions of the TLC plate is unknown.

Topics: Cervix Uteri; Contraceptives, Oral; DNA; DNA Damage; Female; Humans; Isotope Labeling; Phosphorus Radioisotopes; Risk Factors; Smoking; Uterine Cervical Neoplasms

Cervical biopsy samples were taken from 35 women (19 smokers, 5 ex-smokers and 11 non-smokers) aged between 30 and 72, undergoing hysterectomy. DNA was isolated and analysed using 32P-postlabelling, with butanol extraction enhancement of the adducts. Resolution of the adducts was by thin-layer chromatography on polyethyleneimine (PEI)-cellulose. The pattern of adducts was similar to that of smoking-related adducts detected in other tissues and consisted mainly of a diagonal zone of radioactivity. The levels of adducts in DNA from the 19 smokers and a recent ex-smoker ranged from 1.93 to 6.04 adducts/10(8) nucleotides (mean = 3.67, SD = 1.36), in DNA from non-smokers from 1.35 to 3.98 (mean = 2.10, SD = 0.79) and in samples from ex-smokers from 2.57 to 3.35 (mean = 2.86), SD = 0.32). The increase in adduct levels in smokers compared with non-smokers was highly significant (Mann-Whitney test p = 0.002, one-tailed). These results are consistent with the hypothesis that smoking-related cervical cancer results from exposure to genotoxic components of cigarette smoke that become activated to DNA-binding products in this tissue.

Topics: Adult; Aged; Cervix Uteri; DNA; DNA Damage; Female; Humans; Middle Aged; Phosphorus Radioisotopes; Smoking; Uterine Cervical Neoplasms

The presence of human papillomavirus (HPV) in cervical cells is closely related to the development of cervical carcinoma. Detection of virus may be by Southern blot, dot blot or the highly sensitive polymerase chain reaction. Whatever method is employed, there are problems of false negatives due to poor clinical samples in which the DNA may be degraded or is absent altogether. Here we describe a new method of dual labelling for dot blots using a 32P-labelled probe for HPV and a 35S-labelled probe for human actin genes. The samples were counted on a Beta-plate flat-bed scintillation counter and the data analysed to separate the activities of the two isotopes. The counts from the actin probe show whether human DNA is present or not and false negatives from this cause may thereby be eliminated. The counts due to HPV when compared with those for actin give a quantitative measure of HPV abundance for the particular sample and this may have clinical relevance.

Topics: Actins; Cervix Uteri; DNA; Female; Humans; Immunoblotting; Papillomaviridae; Phosphorus Radioisotopes; Sulfur Radioisotopes; Uterine Cervical Neoplasms

Topics: Animals; Apoptosis; Autoradiography; Deoxyadenine Nucleotides; DNA Polymerase I; DNA, Neoplasm; Electrophoresis, Agar Gel; Female; Humans; Indicators and Reagents; Mice; Mice, Nude; Neoplasm Transplantation; Phosphorus Radioisotopes; Protein Biosynthesis; Transplantation, Heterologous; Tumor Cells, Cultured; Uterine Cervical Neoplasms

We describe the detection of eight genital human papillomavirus (HPV) types, including HPV16 and HPV18, by PCR amplification of a 323 base-pair region of the genome within the L1 open reading frame (ORF). The primer sequences are: TGYAAATATCCWGATTWTWT and GTATCWACMACAGTAACAAA. The method will detect purified HPV16 DNA down to a concentration of as little as a single molecule in 100 microliters. The method is also applicable to purified DNA and crude lysates from tumour biopsies. Typing of the PCR product can be achieved with specific oligonucleotide probes.

Topics: Base Sequence; Blotting, Southern; Condylomata Acuminata; DNA, Viral; Female; Humans; Molecular Sequence Data; Nucleic Acid Hybridization; Oligonucleotide Probes; Papillomaviridae; Phosphorus Radioisotopes; Polymerase Chain Reaction; Sensitivity and Specificity; Uterine Cervical Neoplasms

The report deals with a retrospective analysis of applications of different in vivo and in vitro methods of radionuclide studies (1863) in patients with gynecological tumors in 1972-1985. The said methods were employed for making primary diagnosis, assessing tumor extension as well as for evaluating the effects of tumor growth and the efficacy of radiation and surgical treatment. Apart from offering considerable advantages as diagnostic procedures, radionuclide studies may be used in planning treatment modalities and schemes of rehabilitation of cancer patients. The results also suggest a wider application of nuclear procedures in addressing the diagnostic problems of practice of oncology.

Topics: Female; Genital Neoplasms, Female; Gold Colloid, Radioactive; Humans; Iodine Radioisotopes; Methods; Phosphorus Radioisotopes; Radionuclide Imaging; Uterine Cervical Neoplasms; Uterine Neoplasms; Vaginal Neoplasms

Eight cervical biopsies showing mild dysplasia and one showing squamous metaplasia were studied for the presence of papillomavirus (PV) antigens using an immunoperoxidase method having immunospecificity against the genus-specific (common) structural antigen(s) and for PV-specific DNA sequences by molecular hybridization under nonstrigent conditions. Of the eight cases showing mild dysplasia, both PV antigens and PV DNA sequences were detected in five, PV antigens only in one, and PV DNA sequences only in one; viral antigens and DNA sequences were not detected in the remaining lesion. A characteristic cellular atypia (PV-induced atypia) was present in the superficial and intermediate layers of the epithelium in the six cases positive for viral antigens, and a proliferation of basal and parabasal cells (PV-induced hyperplasia) occurred in five of these. PV structural antigens were localized within nuclei of some of the cells displaying atypia but not in the proliferating cells. The PV-specific DNA sequences in all six cases had the properties of unintegrated PV-DNA. In view of the demonstration of both PV antigens and DNA sequences in this distinctive lesion (PV-induced atypia and/or hyperplasia), traditionally regarded as a form of dysplasia, it is proposed that this lesion be referred to as "papillomavirus infection of the cervix."

Topics: Animals; Antigens, Viral; Autoradiography; Biopsy; DNA, Viral; Female; Humans; Immunoenzyme Techniques; Nucleic Acid Hybridization; Papillomaviridae; Phosphorus Radioisotopes; Staining and Labeling; Tumor Virus Infections; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms

One hundred sixty-seven patients with clinical State I carcinoma of the endometrium were treated primarily by operation consisting of total abdominal hysterectomy, bilateral salpingo-oophorectomy, selective pelvic and para-aortic lymphadenectomy, and cytologic testing of peritoneal washings. Twenty-six (15.5%) of the 167 patients had malignant cells identified on cytologic examinations of peritoneal washings. Recurrence developed in 10 of these 26 (34.0%) compared to 14/141 (9.9%) patients with negative cytologic testing. Of the 26 patients, 13 (50%) had disease outside of the uterus at operation and seven have died of disease (54%). Thirteen patients had malignant cells in the peritoneal washings but no disease outside of the uterus and six (46%) of these have died of disseminated intra-abdominal carcinomatosis. On the basis of the poor outcome of those patients who had malignant cells in the peritoneal washings in the 167 patients studied, a plan of treating such patients with intraperitoneal radioactive chromic phosphate suspension (P-32) was instituted. Twenty-three subsequent patients with clinical Stage I carcinoma of the endometrium were found to have malignant cells in the peritoneal fluid. All 23 received intra-abdominal P-32 suspension instillation after operation. There have been three recurrences with two patients dying of disease. All of the three recurrences appeared at sites distant from the abdominal cavity. Peritoneal cytologic examination appears to be an important factor in the prognosis of endometrial cancer and, when the washings are positive for malignant cells, intraperitoneal chronic phosphate therapy appears to be efficacious.

Topics: Adenocarcinoma; Ascitic Fluid; Chromium; Chromium Compounds; Female; Humans; Lymphatic Metastasis; Neoplasm Metastasis; Ovarian Neoplasms; Phosphates; Phosphorus Radioisotopes; Prognosis; Uterine Cervical Neoplasms; Uterine Neoplasms

Topics: Female; Humans; Lymphatic Metastasis; Lymphography; Neoplasm Staging; Phosphorus Radioisotopes; Uterine Cervical Neoplasms

Topics: Adolescent; Adult; Aged; Colposcopy; Cytodiagnosis; Female; Humans; Middle Aged; Phosphorus Radioisotopes; Precancerous Conditions; Sex Chromatin; Uterine Cervical Neoplasms

Topics: Colposcopy; Female; Humans; Phosphorus Radioisotopes; Time Factors; Uterine Cervical Neoplasms; Vaginal Smears

Topics: Adenosine Triphosphatases; Adenylyl Cyclases; Amidohydrolases; Animals; Carcinoma; Carcinoma, Squamous Cell; Cell Line; Cell Membrane; Clone Cells; Female; Fibroblasts; Guinea Pigs; HeLa Cells; Humans; Kinetics; Laryngeal Neoplasms; Liver; Mice; Naphthols; Nasopharyngeal Neoplasms; Neuroblastoma; Nucleotidases; Phosphoric Diester Hydrolases; Phosphoric Monoester Hydrolases; Phosphorus Radioisotopes; Pyrophosphatases; Uterine Cervical Neoplasms

Topics: Female; Humans; Injections, Intralymphatic; Phosphorus Radioisotopes; Uterine Cervical Neoplasms

Topics: Female; Gold Isotopes; Humans; Iodized Oil; Lymph Node Excision; Methods; Phosphorus Radioisotopes; Radioisotopes; Radionuclide Imaging; Uterine Cervical Neoplasms

Topics: Female; Humans; Neoplasms; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Radiometry; Uterine Cervical Neoplasms

Topics: Female; Humans; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Radioactivity; Uterine Cervical Neoplasms; Uterine Neoplasms

Topics: Carcinoma; Diagnosis, Differential; Female; Humans; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Radioactivity; Radiometry; Uterine Cervical Neoplasms

Topics: Female; Humans; Neoplasms; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Uterine Cervical Neoplasms

Topics: Diagnosis, Differential; Female; Humans; Phosphorus; Phosphorus Radioisotopes; Uterine Cervical Neoplasms

Topics: Female; Humans; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Radioactivity; Uterine Cervical Neoplasms

Topics: Female; Humans; Neoplasms; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Radioactivity; Uterine Cervical Neoplasms

Topics: Female; Humans; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Radioactivity; Uterine Cervical Neoplasms

Topics: Female; Humans; Phosphorus; Phosphorus Radioisotopes; Uterine Cervical Neoplasms

Topics: Cervix Uteri; Cobalt; Cobalt Radioisotopes; Female; Humans; Iodine; Iodine Radioisotopes; Neoplasms; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Radioactivity; Radioisotopes; Uterine Cervical Neoplasms; Vaginal Smears

Topics: Cervix Uteri; Cobalt; Cobalt Radioisotopes; Female; Humans; Neoplasms; Phosphorus; Phosphorus Radioisotopes; Phosphorus, Dietary; Radioactivity; Radioisotopes; Uterine Cervical Neoplasms

Topics: Carcinoma; Cervix Uteri; Female; Humans; Neoplasms; Phosphorus; Phosphorus Radioisotopes; Uterine Cervical Neoplasms

Topics: Cervix Uteri; Female; Humans; Neoplasms; Phosphorus; Phosphorus Radioisotopes; Radioactivity; Uterine Cervical Neoplasms