Animals ; DNA Damage ; DNA Repair ; DNA, Neoplasm ; Humans

Recent studies suggest the flow cytometric DNA ploidy analysis may be useful in defining the biologic behavior and prognosis in prostatic adenocarcinoma. Flow cytometric nuclear DNA ploidy analysis was used to study the relationship between DNA ploidy, clinical stage and histopathological grade in thirty two patients with prostatic adenocarcinomas diagnosed from 1987 to 1990. The incidence of aneuploidy in the total population was 18 of 32 (56.3%). The frequency of aneuploidy increased with advancing stage and 63.2% of carcinomas with distant metastases were aneuploidy. Aneuploidy was more frequent in high Gleason sum carcinomas than in low. The incidence of aneuploidy in carcinomas with high Gleason grade (Gleason sum 8 to 10) was 77.8%. comparing to 33.3% in low Gleason grade (Gleason sum 2 to 4). When carcinomas classified according to both DNA ploidy and degree of glandular differentiation, then subgroups with the highest and lowest degree of malignant potential became apparent. None of diploid tumors with low Gleason grade (Gleason sum 2 to 4) formed metastasis, but 71.4% of aneuploidy tumors with high Gleason grade (Gleason sum 8 to 10) formed metastases. The influence of DNA ploidy on survival was examined with Kaplan-Meier method and the generalized Wilcoxon test. Overall, the patients with diploid tumor had a survival advantage over patients with aneuploid tumor (p<0.05). In patients with stage C and D, there was increasing tendency of survival in diploid group. In conclusion flow cytometric determination of DNA ploidy in prostatic adenocarcinoma is correlated strongly with clinical stage and Gleason sum and can be expected to be a valuable adjunct b clinical stage and histopathological grade in the assessment of malignant potential of prostatic adenocarcinoma.
Adenocarcinoma* ; Aneuploidy ; Diploidy ; DNA* ; Humans ; Incidence ; Neoplasm Metastasis ; Ploidies* ; Prognosis

To determine whether the expression of Sialosyl-Tn antigen may have its putative relationship as an established or potentially useful clinicopathologic prognostic parameter in breast cancer, we evaluated 110 patients with invasive breast carcinoma, using formalin-fixed, paraffin-embedded tissue sections. STn antigen was detected by the HB-STn antibody using an avidin-biotin-peroxidase method. The parameters studied were tumor size, nodal status, stage, histologic grade, ER/PR expression, DNA ploidy and S-phase fraction. STn expression was observed in 42 patients (38.2%) with breast cancer. The expression rate of STn was associated with axillary node metastasis. A tendency towards an association between STn expression and tumor size or TNM stage. There was no relationship between STn expression and histologic grade, ER/PR expression, DNA ploidy and S-phase fraction. We conclude that the detection of STn expression may be useful for predicting lymph node metastasis.
Breast Neoplasms* ; Breast* ; DNA ; Humans ; Lymph Nodes ; Neoplasm Metastasis ; Ploidies

DNA, Neoplasm ; Humans ; Image Cytometry ; Pleural Effusion, Malignant ; diagnosis

BACKGROUNDRecent studies suggest that circulating DNA may be a potential tumor marker for lung cancer, but most of these studies are conducted between healthy controls and lung cancer patients, with few or no benign lung disease patients included. The objective of this study was to evaluate the performance of plasma DNA quantification in discriminating lung cancer from the healthy and benign lung disease.

METHODSPlasma DNA was extracted with a QIAamp DNA Blood Midi kit and quantified by a PicoGreen dsDNA quantitation kit in 44 healthy individuals, 36 benign lung disease patients and 67 lung cancer patients. Discrimination power was evaluated by the receiver operating characteristic curve.

RESULTSPlasma DNA values were significantly increased in lung cancer patients, especially in those with metastases, and in benign lung disease patients compared with that in the healthy individuals (P < 0.001, respectively). The values in lung cancer patients were significantly increased compared with that in the benign lung disease patients (P < 0.001). The area under the curve was 0.96 [95% confidence interval (CI) 0.92 - 0.99] for the healthy versus lung cancer, 0.73 (95% CI 0.64 - 0.83) for lung cancer versus benign lung disease, and 0.86 (95% CI 0.80 - 0.91) for lung cancer versus the healthy and benign lung disease.

CONCLUSIONSPlasma DNA quantification has a strong power to discriminate lung cancer from the healthy and from the healthy and benign lung disease, less power to discriminate lung cancer from benign lung disease. Plasma DNA quantification may be useful as a screening tool for lung cancer.

Circulating tumor cells (CTCs) are tumor cells that are separated from the primary site or metastatic lesion and disseminate in blood circulation. CTCs are considered to be part of the long process of cancer metastasis. As a 'liquid biopsy', CTC molecular examination and investigation of single cancer cells create an important opportunity for providing an understanding of cancer biology and the process of metastasis. In the last decade, we have seen dramatic development in defining the role of CTCs in lung cancer in terms of diagnosis, genomic alteration determination, treatment response and, finally, prognosis prediction. The aims of this review are to understand the basic biology and to review methods of detection of CTCs that apply to the various types of solid tumor. Furthermore, we explored clinical applications, including treatment monitoring to anticipate therapy resistance as well as biomarker analysis, in the context of lung cancer. We also explored the potential use of cell-free circulating tumor DNA (ctDNA) in the genomic alteration analysis of lung cancer.
Biology ; Blood Circulation ; Diagnosis ; DNA ; DNA, Neoplasm ; Lung Neoplasms ; Lung ; Methods ; Neoplasm Metastasis ; Neoplastic Cells, Circulating ; Prognosis

PURPOSE: E2F-1 is a transcriptor that converts G1 to S in the cell cycle, and Topoisomerase II-alpha is a key enzyme in the metabolism of DNA, and an indicator of cell replication. The purpose of this study was to evaluate the clinical validity of E2F-1 and Topoisomerase II-alpha as prognostic factors in colorectal cancer. METHODS: The expressions of E2F-1 and Topoisomerase II-alpha were studied immunohistochemically using tumor specimen sections fixed with formalin and paraffin-embedded for 84 cases of colorectal cancer. The correlation between E2F-1 and Topoisomerase II-alpha expressions, and their relationship with the clinicopathological factors, such as tumor differentiation, tumor invasion, lymph node metastasis and tumor stage were investigated. RESULTS: Of the 84 specimens, 43 (51.2%) were immunohistochemically negative for E2F-1, and 41 (48.8%) were positive. The expression of E2F-1 correlated with poor tumor differentiation, increased lymph node metastasis and high tumor stage. The expression of Topoisomerase II-alpha also correlated with poor tumor differentiation, increased lymph node metastasis and high tumor stage. The E2F-1 and Topoisomerase II-alpha expressions indices were significantly correlated. CONCLUSION: These results suggest that the expressions of E2F-1 and DNA Topoisomerase II-alpha may play a role as a prognostic factor for colorectal cancer, but further studies will be required for its comfirmation.
Cell Cycle ; Colorectal Neoplasms* ; DNA ; DNA Topoisomerases, Type I* ; Formaldehyde ; Lymph Nodes ; Metabolism ; Neoplasm Metastasis

PURPOSE: Gene-attenuated replication-competent adenoviruses are emerging as a promising new modality for the treatment of cancer. In an effort to continually improve upon cancer gene therapy, we have modified gene- attenuated replication-competent adenoviruses so as to cause them to replicate efficiently and lyse the infected cancer cells more effectively. MATERIALS AND METHODS: We modified the E1 region of the adenovirus (Ad) systematically, generating Ad-deltaE1B19, Ad-deltaE1B55, Ad-deltaE1B19/55, and Ad-WT. The cytopathic effects (CPE) and viral replication of these four gene modified adenoviruses were compared, and the morphology and DNA fragmentation of the infected cells was evaluated. RESULTS: Among the constructed adenoviruses, E1B 19kD-inactivated adenovirus (Ad-deltaE1B19) was the most potent, inducing the largest-sized plaques and markedCPE. Moreover, cells infected with Ad-deltaE1B19 showed complete cell lysis with disintegrated cellular structure whereas cells infected with Ad-WT maintained intact cellular and nuclear membrane with properly structured organelles. TUNEL assay was also used to monitor DNA integrity, and a more profound induction of apoptosis was observed in the Ad-deltaE1B19 infected cells in comparison to wild type adenovirus infected cells. CONCLUSION: We demonstrate that the inactivation of the E1B19kD gene in a replicating adenovirus leads to increased CPE, rapid viral release, improved cell-to-cell viral spread and increased induction of apoptosis.
Adenoviridae* ; Apoptosis ; Cellular Structures ; DNA ; DNA Fragmentation ; Genes, Neoplasm* ; In Situ Nick-End Labeling ; Nuclear Envelope ; Organelles

No abstract available.
DNA, Neoplasm/genetics ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; Sequence Analysis, DNA/methods ; Urologic Neoplasms/*genetics

DNA Methylation ; DNA, Neoplasm ; genetics ; Genomics ; trends ; Human Genome Project ; Humans ; Neoplasms ; genetics ; Research