A. L. Woods

Bio: A. L. Woods is an academic researcher from Guy's Hospital. The author has contributed to research in topics: Proliferating cell nuclear antigen & Autocrine signalling. The author has an hindex of 2, co-authored 2 publications receiving 1626 citations.

Proliferating cell nuclear antigen (PCNA) immunolocalization in paraffin sections: An index of cell proliferation with evidence of deregulated expression in some, neoplasms

Abstract: Proliferating cell nuclear antigen (PCNA) is a 36 kD nuclear protein associated with the cell cycle A monoclonal antibody, PC10, that recognizes a fixation and processing resistant epitope has been used to investigate its tissue distribution Nuclear PCNA immunoreactivity is found in the proliferative compartment of normal tissues PCNA immunoreactivity is induced in lectin stimulated peripheral blood mononuclear cells in parallel with bromodeoxyuridine incorporation and the number of cells with PCNA immunoreactivity is reduced by induction of differentiation in HL60 cells In non-Hodgkin's lymphomas a linear relation between Ki67 and PCNA staining was demonstrated These data suggest that in normal tissues and lymphoid neoplasms, PCNA immunolocalization can be used as an index of cell proliferation However, in some forms of neoplasia, including breast and gastric cancer and in vitro cell lines, the simple relation between PCNA expression and cell proliferation is lost In some breast and pancreatic tumours there is apparent deregulation of PCNA with increased expression in tissues adjacent to the tumours The over-expression in some tumours and in adjacent morphologically normal tissue may represent autocrine or paracrine growth factor influence on PCNA gene expression

The assessment of proliferating cell nuclear antigen (PCNA)immunostaining in primary gastrointestinal lymphomas and its relationship to histological grade, S + G2 + M phase fraction (flow cytometric analysis) and prognosis.

Abstract: PCNA is a nuclear protein that is synthesized in late G1 and S phases of the cell cycle and is, therefore, correlated with the cell proliferative state. A new monoclonal antibody (PC10) to genetically engineered PCNA has been shown to label proliferating cells in formalin-fixed paraffin-embedded normal human tissues. Previous studies in lymphomas, using various markers of cell proliferation, have shown a strong correlation between indices of cell proliferation and histological grade. These studies have shown that within each histological subtype there is often a wide range of proliferative indices and that these may be of some prognostic significance. Thirty-one gastrointestinal lymphomas were studied. Our results show that there is a good correlation between PC10 index and histological grade of tumour (0.01 P greater than P greater than 0.001) and also a significant relationship between PC10 index and S+G2+M phase fraction as measured by flow cytometric analysis (r2 = 0.62; P less than 0.01). Twenty-three cases were available for survival analysis. In these cases a high PC10 score correlated with poor survival (P = 0.04). Based on this series, it appears that there is a significant relationship between PC10 index and histological grade, and between PC10 index and S+G2+M phase as measured by flow cytometric analysis. In addition, our results suggest that a high PC10 index is an adverse prognostic factor in primary gastrointestinal lymphoma.

The cell proliferation-associated antigen of antibody Ki-67: a very large, ubiquitous nuclear protein with numerous repeated elements, representing a new kind of cell cycle-maintaining proteins.

Abstract: The antigen defined by mAb Ki-67 is a human nuclear protein the expression of which is strictly associated with cell proliferation and which is widely used in routine pathology as a "proliferation marker" to measure the growth fraction of cells in human tumors. Ki-67 detects a double band with apparent molecular weights of 395 and 345 kD in immunoblots of proteins from proliferating cells. We cloned and sequenced the full length cDNA, identified two differentially spliced isoforms of mRNA with open reading frames of 9,768 and 8,688 bp encoding for this cell proliferation-associated protein with calculated molecular weights of 358,761 D and 319,508 D, respectively. New mAbs against a bacterially expressed part and a synthetic polypeptide deduced from the isolated cDNA react with the native Ki-67 antigen, thus providing a circle of evidence that we have cloned the authentic Ki-67 antigen cDNA. The central part of the Ki-67 antigen cDNA contains a large 6,845-bp exon with 16 tandemly repeated 366-bp elements, the "Ki-67 repeats", each including a highly conserved new motif of 66 bp, the "Ki-67 motif", which encodes for the epitope detected by Ki-67. Computer analysis of the nucleic acid and the deduced amino acid sequence of the Ki-67 antigen confirmed that the cDNA encodes for a nuclear and short-lived protein without any significant homology to known sequences. Ki-67 antigen-specific antisense oligonucleotides inhibit the proliferation of IM-9 cell line cells, indicating that the Ki-67 antigen may be an absolute requirement for maintaining cell proliferation. We conclude that the Ki-67 antigen defines a new category of cell cycle-associated nuclear nonhistone proteins.

The Cell Cycle: A Review:

Abstract: The cell cycle is a complex process that involves numerous regulatory proteins that direct the cell through a specific sequence of events culminating in mitosis and the production of two daughter cells. Central to this process are the cyclin-dependent kinases (cdks), which complex with the cyclin proteins. These proteins regulate the cell's progression through the stages of the cell cycle and are in turn regulated by numerous proteins, including p53, p21, p16, and cdc25. Downstream targets of cyclin-cdk complexes include pRb and E2F. The cell cycle can be altered to the advantage of many viral agents, most notably polyomaviruses, papillomaviruses, and adenoviruses. The cell cycle often is dysregulated in neoplasia due to alterations either in oncogenes that indirectly affect the cell cycle or in tumor suppressor genes or oncogenes that directly impact cell cycle regulation, such as pRb, p53, p16, cyclin D1, or mdm-2. The cell cycle has become an intense subject of research in recent years. This research has led to the development of techniques useful for the determination of the effects of drugs and toxins on the cell cycle. Any drug or toxin with DNA damaging ability would be expected to alter cell cycle progression, and therefore, the cell cycle should be considered in the design of studies using such chemicals. With the appropriate techniques, cell cycle alterations may also be detected in tissue sections. Because of the ubiquitous nature of the cell cycle, it deserves consideration in the design and interpretation of studies in a wide variety of disciplines.

Increased manganese superoxide dismutase expression suppresses the malignant phenotype of human melanoma cells.

Abstract: Introduction of a normal human chromosome 6 into human melanoma cell lines results in suppression of tumorigenicity. This suggests that a gene(s) on chromosome 6 controls the malignant phenotype of human melanoma. Because antioxidants can suppress the tumor-promotion phase of carcinogenesis, and because the antioxidant enzyme manganese superoxide dismutase (MnSOD) has been localized to a region of chromosome 6 frequently lost in melanomas, we have examined the effect of transfecting sense and antisense human MnSOD cDNAs into melanoma cell lines. Cell lines expressing abundant (+)-sense MnSOD-5 cDNAs significantly altered their phenotype in culture and lost their ability to form colonies in soft agar and tumors in nude mice. In contrast, the introduction of antisense MnSOD or +psv2neo had no effect on melanoma tumorigenicity. These findings indicate that stable transfection of MnSOD cDNA into melanoma cell lines exerts a biological effect that mimics that observed after introduction of an entire human chromosome 6.