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Query: UMLS:C0006826 (cancer)
 1,092,456 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cell cycle arrest in G2 phase is a common response to a variety of DNA-damaging agents. The coupling between DNA damage and G2 arrest was studied in synchronized HeLa cells using camptothecin, a highly specific inhibitor of topoisomerase I that damages DNA through the formation of reversible topoisomerase I-DNA cleavable complexes. Brief camptothecin treatment of early S-phase HeLa cells caused arrest at G2 phase and abolished the activation of p34cdc2 protein kinase. Both tyrosine dephosphorylation of p34cdc2 and cyclin B accumulation were altered. These cell cycle-dependent changes were not observed when DNA replication was inhibited by aphidicolin during the brief camptothecin treatment. Our results suggest that to produce G2 arrest, active DNA synthesis is required at the time of camptothecin treatment, as was previously shown for camptothecin-induced cytotoxicity. Furthermore, our results suggest that the interaction of the replication fork with DNA damage may ultimately trigger altered regulation of p34cdc2/cyclin B, leading to cell cycle arrest at the G2 phase.
Cancer Res 1992 Apr 01
PMID:The involvement of active DNA synthesis in camptothecin-induced G2 arrest: altered regulation of p34cdc2/cyclin B. 131

The presence of IGF-I and IGF-I receptors in human midgut carcinoid tumours has been investigated. Using immunocytochemistry, IGF-I-positive tumour cells were demonstrated in 11/11 tumour cases studied. Labelling of consecutive sections with antibodies against IGF-I and proliferating cell nuclear antigen (PCNA)/cyclin demonstrated a co-distribution of the 2 antigens in carcinoid tumours. Extracts of tumour tissues were subjected to radioimmunoassay and shown to contain significant amounts of IGF-I. Reverse-phase HPLC of tumour extracts demonstrated a major IGF-I-immunoreactive component eluting in the position of rhIGF-I, but also 2 other more hydrophobic forms. Conditioned serum-free media from primary cultures of carcinoid tumors contained detectable amounts of IGF-I, indicating a spontaneous release of IGF-I from tumour cells into the culture medium. Levels of IGF-I in media were reduced (19%) after incubation of cultures with a somatostatin analogue for 4 days. IGF-I receptors were observed on tumour cells in 4/10 tumours by immunocytochemistry. Tumour cells with immunoreactive IGF-I receptors could be stimulated to enhanced growth, measured as an increase in DNA contents, by exogenous administration of IGF-I every 3-4 days for 2 weeks. The results show that cultured human midgut carcinoid tumours secrete IGF-I and that some of the tumours also have IGF-I receptors. We therefore suggest that IGF-I may act as an autocrine or paracrine regulator of carcinoid tumour-cell growth.
Int J Cancer 1992 May 08
PMID:Presence of IGF-I in human midgut carcinoid tumours--an autocrine regulator of carcinoid tumour growth? 131 81

A universal intracellular factor, the "M phase-promoting factor" (MPF), triggers the G2/M transition of the cell cycle in all organisms. In late G2, it is present as an inactive complex of tyrosine-phosphorylated p34cdc2 and unphosphorylated cyclin Bcdc13. In M phase, its activation as an active MPF displaying histone H1 kinase activity originates from the specific tyrosine dephosphorylation of the p34cdc2 subunit by the tyrosine phosphatase p80cdc25. We describe here a colorimetric assay of recombinant human cdc25A tyrosine phosphatase used as a cell cycle-specific target to screen for antimitotic compounds. The glutathione-S-transferase/cdc25A tyrosine phosphatase fusion protein is produced in large amounts of Escherichia coli and easily purified by affinity chromatography on glutathione-agarose. Optimal purification, storage and assay conditions (concentrations of enzyme, p-nitrophenylphosphate and dithiothreitol; duration of assay) have been determined. Using this system we tested 15 compounds currently used in cancer treatment; none of them displayed any inhibitory activity. However, the assay detected the inhibitory activity of vanadate, a reported tyrosine phosphatase inhibitor. The simplicity, speed and possible extensive automation of this assay using an essential cell cycle-regulating component provide a highly specific mechanism-based screen for antimitotic drugs discovery.
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PMID:Screening for antimitotic compounds using the cdc25 tyrosine phosphatase, an activator of the mitosis-inducing p34cdc2/cyclin Bcdc13 protein kinase. 132 Mar 60

The authors studied histochemically the morphologic features of proliferating hepatocytes positive for proliferating cell nuclear antigen (PCNA/cyclin) to analyze the process of liver regeneration in embedded tissues fixed with formaldehyde using an anti-PCNA/cyclin monoclonal antibody. In liver specimens from patients with acute viral hepatitis (AVH) and confluent necrosis, many small basophilic hepatocytes surrounding large clear hepatocytes were positively stained in the areas next to the confluent necrosis. Therefore these small hepatocytes may be daughter cells derived from large clear hepatocytes that probably enter the mitotic cell cycle repeatedly to repair a large necrotic area. In the case of AVH with spotty necrosis, the positively stained hepatocytes were scattered around the necrotic foci. In the liver specimens from patients with chronic active hepatitis, most of the positively stained hepatocytes were located next to the necrotic area. As for cirrhosis of the liver, the number of hepatocytes positive for PCNA/cyclin varied greatly in different pseudolobules, and in the specimens of hepatocellular carcinoma (HCC), the HCC cells positive for PCNA/cyclin were detected throughout the cancer nests.
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PMID:Analysis of proliferating hepatocytes using a monoclonal antibody against proliferating cell nuclear antigen/cyclin in embedded tissues from various liver diseases fixed in formaldehyde. 134 35

Cell proliferation of transitional cell bladder cancer (TCC) was determined by PCNA (proliferating cell nuclear antigen)/cyclin immunostaining in 178 TCCs and the results were related to established prognostic factors, progression and survival during a mean follow-up period of 10 years. The fraction of PCNA/cyclin positive nuclei was related to T-category (P = 0.008), papillary status, WHO grade, DNA ploidy, S phase fraction, M/V index (volume corrected mitotic index) and AgNORs (silver stained nucleolar organiser regions) (for all P less than 0.001). TCCs presenting with pelvic lymph node metastasis at diagnosis had a significantly higher growth fraction than the tumours confined to the bladder wall (P less than 0.001). The fraction of PCNA/cyclin positive nuclei predicted progression in T-, N- and M-categories (P less than 0.001). In Ta-T1 tumours high fraction of PCNA/cyclin positive nuclei predicted metastasis (P = 0.019). In survival analysis the fraction of PCNA/cyclin positive nuclei predicted survival in the entire cohort (P less than 0.001) and in Ta-T1 tumours (P = 0.0005). In a multivariate survival analysis the fraction of PCNA/cyclin positive nuclei showed independent predictive value in the entire cohort (P = 0.046), in papillary tumours (P = 0.006) and in Ta-T1 tumours (P = 0.015). The results show that the growth fraction as determined by PCNA/cyclin immunostaining is a significant prognostic variable in TCC.
Br J Cancer 1992 Jul
PMID:Cell proliferation of transitional cell bladder tumours determined by PCNA/cyclin immunostaining and its prognostic value. 135 64

Comparative studies of ploidy and proliferative activity of spindle cells in sections of 20 (skin, 17; lymph node, 3) biopsy specimens from African patients, 10 with endemic Kaposi's sarcoma (EKS) and 10 with AIDS-associated Kaposi's sarcoma (AKS) were performed by histopathology, feulgen-based DNA measurement and proliferating cell nuclear antigen (PCNA)/cyclin immunohistochemistry, respectively. All specimens were classified as nodular lesions with basically the same histology. In 17 cases immunostained for cyclin/PCNA, the percentage of proliferating spindle cells range between 2-18, with a higher mean rate in AKS although this was not statistically significant. In situ measurement of DNA showed no significant values greater than the diploid level of control cells indicating that spindle cells in both EKS and AKS have euploid DNA content. Our findings indicate that both EKS and AKS represent the same type of euploid low rate cell proliferations. This corroborates previous suggestions that KS could represent a reactive process to yet undefined stimulus rather than a clonal proliferation, of transformed malignant cells.
Eur J Cancer 1992
PMID:Spindle cell ploidy and proliferation in endemic and epidemic African Kaposi's sarcoma. 135 89

The proliferative activity of pharyngeal carcinoma has been investigated by means of monoclonal antibody PC10 against proliferating cell nuclear antigen (PCNA/cyclin) and argyrophilic nucleolar organizer region (AgNOR) analysis in formalin-fixed, paraffin-embedded biopsies from 45 primary squamous and undifferentiated carcinomas, prior to therapy. The correlation between AgNOR counts and PCNA(PC10) scores was highly significant (r = 0.73; P < 0.0001) as determined by Pearson's correlation coefficient. Moreover, the univariate Kaplan-Meier survival analysis showed a significant correlation between 3- and 5-year survival rates and the mean AgNOR number per tumour cell (P = 0.0003) or the percentage of PCNA(PC10)-positive cells (P = 0.0001). Our results indicate that both AgNOR counts and PCNA(PC10) scores are reliable markers of the proliferative activity of pharyngeal carcinoma in small, routinely processed biopsies, in which they can allow simultaneous evaluation of the histology and tumour cell kinetics.
J Cancer Res Clin Oncol 1992
PMID:Argyrophilic nucleolar organizer region counts and proliferating cell nuclear antigen scores are two reliable indicators of survival in pharyngeal carcinoma. 135 93

Cytogeneticists first proposed that the karyotypic abnormalities identified on chromosomes 1, 3, 6, 11, 13, 16, 17, and 18 supported a genetic basis for breast cancer. Such abnormal banding patterns, however, may represent either loss-of-function or gain-of-function molecular events. RFLP analyses have since confirmed that 20-60% of primary and spontaneous human breast tumors exhibit allelic losses on these same chromosomes, although the exact genes involved at these chromosomal sites remain largely unknown. Knowledge gained about the Rb-1 and p53 tumor suppressor genes at 13q14 and 17p13 in breast and other human tumors supports the paradigm that for any chromosomal locus, allelic loss associated with a mutation in the remaining tumor allele signifies an involved tumor suppressor gene. Given this paradigm, there are nearly a dozen putative breast tumor suppressor genes under active investigation, with most investigators now focusing on various chromosome 17 loci. Among the known proto-oncogenes found activated in breast cancer, amplification of c-erbB-2 at 17q21 is the most widely studied and clinically significant gain-of-function event uncovered to date, occurring in about 20% of all primary breast tumors. The involvement of this overexpressed membrane receptor has engendered interest in related tyrosine kinase receptors, such as EGFR, IR, and IGF-I-R, as well as their respective ligands, which may be overexpressed in a greater fraction of tumors, contributing to the autocrine and paracrine regulation of breast cancer growth and metastasis. New attention is being given to the potentially oncogenic function of structurally altered nuclear transactivating steroid hormone receptors, such as ER, whose overexpression has long been used to determine endocrine therapy and prognosis for individual breast cancer patients. While c-myc was one of the first known proto-oncogenes to be found amplified and overexpressed in human breast cancers, the actual incidence and clinical significance of its activation remain disputed and in need of further study. Lastly, we can expect greater clarification about the importance of various 11q13 genes found coamplified in nearly 20% of primary breast cancers, and pursuit into the intriguing possibility that a cyclin-encoding gene represents the overexpressed locus of real interest in this amplicon. Virtually all of these important genetic abnormalities identified thus far are associated with but not restricted to human breast cancers. The absence of identifiable molecular defects relating to the tissue specificity of this malignancy must be considered a substantial gap in our basic understanding of breast carcinogenesis.(ABSTRACT TRUNCATED AT 400 WORDS)
Cancer Treat Res 1992
PMID:Activated oncogenes and putative tumor suppressor genes involved in human breast cancers. 136 56

The effect of quercetin, a flavonoid found in many plants, on the proliferation of human leukemic T-cells was analyzed. Quercetin reversibly blocked the cell cycle at a point 3-6 h before the start of DNA synthesis. Expression of the growth-related genes histone H4, cyclin A and B, and p34cdc2 was suppressed in cells blocked with quercetin. Comparison of the quercetin arrest points with those of the cell cycle inhibitors aphidicolin and mimosine revealed a temporal order of arrest points in G1 of quercetin, mimosine, and aphidicolin. Mimosine and aphidicolin did not inhibit the expression of cyclin A or p34cdc2, whereas all three reagents inhibited expression of cyclin B. Low concentrations of the protein inhibitor cycloheximide inhibited release of the quercetin but not the mimosine or aphidicolin block. A [35S]methionine-labeled M(r) 60,000 protein disappeared in quercetin-treated cells and was rapidly synthesized after removal of quercetin, suggesting the possibility that the M(r) 60,000 protein induces DNA synthesis after the cell is released from a quercetin block. These results suggest the usefulness of quercetin in studies of the regulation of late G1 phase.
Cancer Res 1992 Dec 01
PMID:Quercetin arrests human leukemic T-cells in late G1 phase of the cell cycle. 142 13

The clockwise concept of cell cycle kinetics has changed since molecular biology made rapid advances in this area and added somewhat to cell cycle analysis by DNA histogram. During the last decade, it has been made possible to measure many cell-cycle-regulating gene products flow cytometrically. Application of bromodeoxyuridine (BrdU) to cell cycle analysis contributes to scientific progression in many fields of biology and oncology. In this article, we attempt to summarize the outline of new concepts regarding the cell cycle by means of flow cytometric techniques and to describe their application in biology and oncology. For this purpose, probes, biological differences amongst the dyes used, DNA analysis using DNA histograms and their limitations are explained. Next, new methods to analyse cell cycle kinetics by means of BrdU, Ki-67 antigen, cyclin, etc. discussed. As far as application of flow cytometric cell cycle analysis are concerned, influences of nutrition, growth factors and hormones, relationships between DNA index or cell cycle and the prognosis of patients with cancer, and the effect of anticancer drugs on the cell cycle are discussed. Finally, we emphasize the importance of multiparameter analysis of cell cycle kinetics using flow cytometry.
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PMID:[The theory of flow cytometric analysis of the cell cycle and their applications in biology and oncology]. 144 2


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