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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Presence of IGF-I in human midgut carcinoid tumours--an autocrine regulator of carcinoid tumour growth? 131 81

We have previously reported the identification of a hepatitis B virus (HBV) DNA integration in an intron of the cyclin A gene in an early hepatocellular carcinoma (HCC) and the isolation of human cyclin A cDNA. We have now constructed a cDNA library from the tumor and isolated several hybrid HBV-cyclin A cDNAs from it. The hybrid cDNAs encode an HBV-cyclin A fusion protein. In the chimeric protein, the N-terminus of cyclin A, including the signals for cyclin degradation, is deleted and replaced by viral PreS2/S sequences, transcription being initiated from the viral PreS2/S promoter. This chimeric protein is undegradable in an in vitro cyclin degradation assay. Northern blot analyses showed strong expression of the hybrid transcripts in the tumor, while cyclin A- or HBV-specific transcripts were not detected in the non-tumorous liver of the same patient. Thus, HBV DNA integration in the cyclin A gene resulted in a strong expression of hybrid HBV-cyclin A transcripts encoding a stabilized cyclin A. This chimeric protein may play an important role in the development of the tumor.
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PMID:Modification of cyclin A expression by hepatitis B virus DNA integration in a hepatocellular carcinoma. 132 6

Expression of proliferating cell nuclear antigen/cyclin (PCNA/cyclin) in skin tissue specimens and cultured keratinocytes was studied using a monospecific antibody, obtained from a patient with systemic lupus erythematosus, and a monoclonal antibody. Indirect immunofluorescent staining revealed that cultured keratinocytes obtained from human foreskins expressed PCNA/cyclin as variable nuclear patterns in 15-30% of the cells. In normal human skin tissue specimens, PCNA/cyclin was demonstrated in only a few basal cells. Interestingly, PCNA/cyclin was expressed strongly in almost all the cells of the lowest layer of the epidermis adjacent to squamous cell carcinomas, whereas the tumor aggregates themselves had no positive staining. In contrast, no such characteristic staining was demonstrated in specimens of basal cell carcinoma. The staining pattern of PCNA/cyclin was different from that of Ki-67 in the skin tissue specimens. Our results suggest that PCNA/cyclin could be a useful marker of cell proliferation.
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PMID:Immunohistochemical localization of proliferating cell nuclear antigen/cyclin in human skin. 135 13

Tumor proliferative activity, or labeling index, is of interest for gaining insight into the biologic properties of human neoplasm and for providing clinical information that might guide patient management. There has been an abundance of literature reporting experience with standard and newer techniques of measuring tumor proliferative activity. These methods are reviewed with emphasis on technical issues. Particular attention is paid to the development and use of monoclonal antibodies, Ki-67 and anti-PCNA/cyclin. These antibodies are readily available and relatively simple to use. The former has recently been shown to be of prognostic value in non-Hodgkin's large cell lymphomas. A number of studies suggest that indices using these techniques could be useful for a variety of carcinomas, soft tissue tumors, and tumors of the central nervous system.
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PMID:Measures of tumor proliferative activity. 136 73

We determined the proliferative index (PI) of 92 previously untreated advanced epithelial ovarian cancers using PCNA/cyclin immunostaining and image analysis quantitation. In this retrospective study, there was a relationship between tumor PI and 5-year survival. For patients with a tumor PI greater than the median, the estimated 5-year survival was 44%; for patients with a tumor PI below the median, the estimated 5-year survival was 15% (P = 0.003). This may partly reflect sensitivity to chemotherapy, as those patients with more rapidly proliferating tumors were more likely to achieve a pathologic complete response to platinum-based therapy.
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PMID:Proliferating cell nuclear antigen in epithelial ovarian cancer: relation to results at second-look laparotomy and survival. 136 79

The bromodeoxyuridine (BrdU) labeling study provides valuable cell kinetic information for individual tumors that could suggest the prognosis of each patient who had a tumor. Recently, a monoclonal antibody against the proliferating cell nuclear antigen (PCNA or cyclin), a nuclear protein expressed in proliferating cells, was developed which could be used on formalin fixed, paraffin embedded tissue. The purpose of this study was to compare the cell kinetic data obtained by the BrdU labeling study and the PCNA method in the same patient. The relationship between labeling indices of BrdU incorporated into S-phase and PCNA expressed by cycling cells was investigated in 31 patients with brain tumors. Both of the labeling indices showed good correlation with histological grade of the tumor. The values of the PCNA labeling index (LI) were parallel but higher than those of the BrdU LI, and the relation PCNA LI = 2.2 x BrdU LI + 0.8 (r2 = 0.86) was obtained. The results of this study show that PCNA could replace the BrdU method for identifying the proliferating cells, and the major advantages of PCNA method is that it could be done without any pretreatment and avoid injection of the teratogenic agent for diagnostic purpose.
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PMID:Comparison of brain tumor growth kinetics by proliferating cell nuclear antigen (PCNA) and bromodeoxyuridine (BrdU) labeling. 136 39

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)
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PMID:Activated oncogenes and putative tumor suppressor genes involved in human breast cancers. 136 56

The authors investigated whether immunocytochemical staining with a monoclonal antibody to proliferating cell nuclear antigen (PCNA/cyclin) could be used to identify proliferative hepatocytes in frozen sections fixed in a mixture of periodate, lysine, and 2% paraformaldehyde. Paraffin sections also were used, which were fixed in 10% formaldehyde. Specimens of liver tissue were obtained from 27 patients with various hepatic diseases. Hepatocytes that were positive for PCNA/cyclin were observed in both types of substrate specimens. In acute hepatitis and chronic active hepatitis, most hepatocytes that were labeled for PCNA/cyclin were located near necrotic foci. However, in cirrhosis, they were detected most often near fibrotic septa; the number of immunoreactive cells varied greatly in different areas of tissue sections in such cases. In hepatocellular carcinoma, many PCNA/cyclin-positive tumor cells were seen throughout the neoplasms. Hepatocytes that were positive for DNA polymerase-alpha showed a similar distribution pattern in serial sections of study cases.
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PMID:Immunocytochemical identification of proliferative hepatocytes using monoclonal antibody to proliferating cell nuclear antigen (PCNA/cyclin). Comparison with immunocytochemical staining for DNA polymerase-alpha. 137 17

Recent studies of cell cycle control suggest that cyclin-dependent protein kinases play a central role in the cell's commitment to a new division cycle in late G1. The regulation of these kinases in normal and neoplastic growth is becoming clear.
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PMID:Cell cycle control in normal and neoplastic cells. 138 97

Hyperparathyroidism is a central component of multiple endocrine neoplasia type 1 (MEN 1), and both sporadic and familial forms of parathyroid disease may share certain pathogenetic features. We recently identified a gene that is clonally rearranged with the PTH locus in a subset of sporadic parathyroid adenomas. This candidate oncogene, PRAD1 (previously D11S287), appears to contribute to parathyroid tumorigenesis in a fashion analogous to activation of C-MYC or BCL-2 by rearrangement with tissue-specific enhancers of the immunoglobulin genes in B-lymphoid neoplasia. The PRAD1 gene maps to 11q13 and has been linked to the BCL-1 breakpoint locus, although not to the most tightly linked MEN 1 markers, by pulsed field gel electrophoresis. PRAD1 may, in fact, be the long-sought BCL-1 lymphoma oncogene. PRAD1 encodes a novel type of cyclin protein and thus may normally function in controlling the cell cycle, perhaps through direct interaction with cdc2 or a related kinase. PRAD1's possible primary, or more likely secondary, involvement in the pathogenesis of MEN 1-related tumors is unknown and under investigation.
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PMID:PRAD1 (cyclin D1): a parathyroid neoplasia gene on 11q13. 148 73


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