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Results for “Proliferation”

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PubMed2003

In human hepatocellular carcinoma in cirrhosis proliferating cell nuclear antigen (PCNA) is involved in cell proliferation and cooperates with P21 in DNA repair.

BACKGROUND: Proliferating cell nuclear antigen (PCNA) is a nuclear protein involved in DNA-synthesis and repair. During DNA-synthesis and repair the only active PCNA fraction is tightly bound to DNA. Similarly, during DNA-repair, a fraction of p21 colocalizes with PCNA in a detergent-insoluble form. AIM: The aim of the study was to analyze to what extent the presence of DNA-bound PCNA and p21 correlates with cell proliferation and DNA-repair in hepatocellular carcinoma (HCC). METHODS: Twenty-six HCCs and surrounding cirrhosis were studied. The DNA-bound and detergent-soluble fractions of PCNA and p21 were analyzed by immunoblotting. P53 and Ki67-Labeling Index (Ki67-LI) were evaluated by immunocytochemistry. RESULTS: Soluble fractions of PCNA and p21 were found in all samples. One out of 26 cirrhotic samples displayed a DNA-bound fraction of PCNA while no case expressed DNA-bound p21. Fourteen HCCs showed a DNA-bound PCNA fraction. A highly significant correlation was found between Ki67-LI and DNA-bound PCNA but not with detergent-soluble PCNA. DNA-bound p21 and PCNA, indicating ongoing DNA repair activity, were present in 6 of these 14 HCCs and correlated with a high histological grade and high Ki67-LI. CONCLUSIONS: Our results suggest that in HCC PCNA participates both in DNA synthesis and repair and that highly proliferating HCCs may display a sustained DNA-repair.

Adult↗

PubMed2001

The short heterodimer partner receptor differentially modulates peroxisome proliferator-activated receptor alpha-mediated transcription from the peroxisome proliferator-response elements of the genes encoding the peroxisomal beta-oxidation enzymes acyl-CoA oxidase and hydratase-dehydrogenase.

The promoter regions of the genes encoding the first two enzymes of the peroxisomal beta-oxidation pathway, acyl-CoA oxidase (AOx) and enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase (HD), contain transcriptional regulatory sequences termed peroxisome proliferator-response elements (PPRE) that are bound by the peroxisome proliferator-activated receptor alpha (PPARalpha) and 9-cis-retinoic acid receptor (RXRalpha) heterodimeric complex. In this study, the role of the short heterodimer partner (SHP) receptor in modulating PPARalpha-mediated gene transcription from the PPREs of the genes encoding AOx and HD was investigated both in vitro and in vivo. In vitro binding assays using glutathione-S-transferase-tagged chimeric receptors for PPARalpha and SHP were used to verify the interaction between PPARalpha and SHP. This interaction was unaffected by the presence of the peroxisome proliferator, Wy-14,643. SHP has been proposed to act as a negative regulator of nuclear hormone receptor activity, and SHP inhibited transcription by PPARalpha/RXRalpha heterodimers from the AOx-PPRE. Surprisingly, SHP potentiated transcription by PPARalpha/RXRalpha heterodimers from the HD-PPRE. This is the first demonstration of positive transcriptional activity attributable to SHP. Together, these results suggest that SHP can modulate PPARalpha/RXRalpha-mediated transcription in a response element-specific manner.

3-Hydroxyacyl CoA Dehydrogenases↗

PubMed2005

Breast carcinoma malignancy grading by Bloom-Richardson system vs proliferation index: reproducibility of grade and advantages of proliferation index.

Questions of reproducibility and efficacy of histologic malignancy grading relative to alternative proliferation index measurements for outcome prediction remain unanswered. Microsections of specimens from the Cooperative Breast Cancer Tissue Resource (CBCTR) were evaluated by seven pathologists for reproducibility of grade and classification. Nuclear figure classification was assessed using photographs. Grade was assigned by the Bloom-Richardson method, Nottingham modification. Proliferation index was evaluated prospectively by deoxyribose nucleic acid precursor uptake with thymidine (autoradiographic) or bromodeoxyuridine (immunohistochemical) labeling index using fresh tissue from 631 node-negative breast cancer patients accessioned at St Luke's Hospital. A modified Nottingham-Bloom-Richardson grade was derived from histopathologic data. Median post-treatment observation was 6.4 years. Agreement on classification of nuclear figures (N=43) was less than good by kappa statistic (kappa=0.38). Grade was moderately reproducible in four trials (N=10,10,19, 10) with CBCTR specimens (kappa=0.50-0.59). Of components of Bloom-Richardson grade, agreement was least for nuclear pleomorphism (kappa=0.37-0.50), best for tubularity (kappa=0.57-0.83), and intermediate for mitotic count (kappa=0.45-0.64). Bloom-Richardson grade was a univariate predictor of prognosis in node-negative St Luke's patients, and was improved when mitotic count was replaced by labeling index (low, mid, or high). When labeling index was added to a multivariate model containing tumor size and vessel invasion, grade was no longer a significant predictor of tumor-specific relapse-free or overall survival. Mitotic index predicted best when intervals were lowered to 0-2, 3-10, and >10 mitotic figures per ten 0.18 mm(2) high-power fields. We conclude that Nottingham-Bloom-Richardson grades remain only modestly reproducible. Prognostically useful components of grade are mitotic index and tubularity. The Nottingham-Bloom-Richardson system can be improved by lowering cutoffs for mitotic index and by counting 20-30 rather than 10 high-power fields. Measurement of proliferation index by immunohistochemically detectable markers will probably give superior prognostic results in comparison to grade.

Breast Neoplasms↗

PubMed2006

Peroxisome proliferator-activated receptor gamma-mediated regulation of neural stem cell proliferation and differentiation.

Peroxisome proliferator-activated receptor gamma (PPARgamma) plays an important role in insulin sensitivity, tissue homeostasis, and regulating cellular functions. We found high-level expression of PPARgamma in embryo mouse brain and neural stem cells (NSCs), in contrast to extremely low levels in adult mouse brain. Here, we show that PPARgamma mediates the proliferation and differentiation of murine NSCs via up-regulation of the epidermal growth factor receptor and activation of the ERK pathway. Cell growth rates of NSCs prepared from heterozygous PPARgamma-deficient mouse brains, PPARgamma-RNA-silenced NSCs, and PPARgamma dominant-negative NSCs were significantly decreased compared with those of wild-type NSCs. Physiological concentrations of PPARgamma agonists, rosiglitazone and pioglitazone, stimulated NSC growth, whereas antagonists caused cell death in a concentration-dependent manner via activation of the caspase cascade. The stimulation of cell growth by PPARgamma was associated with a rapid activation of the ERK pathway by phosphorylation and up-regulation of epidermal growth factor receptor and cyclin B protein levels. In contrast, activation of PPARgamma by agonists inhibited the differentiation of NSCs into neurons. The inhibition of differentiation was associated with an activation of STAT3. These data indicate that PPARgamma regulates the development of the central nervous system during early embryogenesis via control of NSC proliferation.

Animals↗

PubMed2006

Attenuation of peroxisome proliferator-activated receptor gamma (PPARgamma) mediates gastrin-stimulated colorectal cancer cell proliferation.

Peroxisome proliferators-activated receptor gamma (PPARgamma) has been shown to suppress cell proliferation and tumorigenesis, whereas the gastrointestinal regulatory peptide gastrin stimulates the growth of neoplastic cells. The present studies were directed to determine whether changes in PPARgamma expression might mediate the effects of gastrin on the proliferation of colorectal cancer (CRC). Initially, using growth assays, we determined that the human CRC cell line DLD-1 expressed both functional PPARgamma and gastrin receptors. Amidated gastrin (G-17) attenuated the growth suppressing effects of PPARgamma by decreasing PPARgamma activity and total protein expression, in part through an increase in the rate of proteasomal degradation. G-17-induced degradation of PPARgamma appeared to be mediated through phosphorylation of PPARgamma at serine 84 by a process involving the biphasic phosphorylation of ERK1/2 and activation of the epidermal growth factor receptor (EGFR). These results were confirmed through the use of EGFR antagonist AG1478 and MEK1 inhibitor PD98059. Furthermore, mutation of PPARgamma at serine 84 reduced the effects of G-17, as evident by inability of G-17 to attenuate PPARgamma promoter activity, degrade PPARgamma, or inhibit the growth suppressing effects of PPARgamma. The results of these studies demonstrate that the trophic properties of gastrin in CRC may be mediated in part by transactivation of the EGFR and phosphorylation of ERK1/2, leading to degradation of PPARgamma protein and a decrease in PPARgamma activation.

Animals↗

PubMed2006

Cell proliferation rate and telomerase activity in the differential diagnosis between benign and malignant mesothelial proliferations.

AIMS: The differential diagnosis of malignant mesothelioma (MM) from benign mesothelial lesions (BML) based on histopathological criteria is sometimes not satisfying and causes diagnostic problems for histopathologists. We aimed to investigate whether the immunohistochemically determined cell proliferation rate and telomerase activity, using Ki-67 and human telomerase reverse transcriptase (hTERT) immunohistochemistry, respectively, are useful in the differential diagnosis of MM from BML. METHODS: Sixty-six cases of MM (33 epithelioid, 30 biphasic and 3 sarcomatoid) and 22 cases of BML (15 reactive mesothelial proliferations and 7 fibrous pleuritis/pericarditis) were included in this study. We evaluated the proliferative activity by Ki-67 and telomerase activity by hTERT immunohistochemistries for each case. RESULTS: The mean value of the Ki-67 proliferation index (PI) in MMs was significantly higher than that of BMLs. Biphasic MMs have higher a Ki-67 PI than epithelioid and sarcomatoid types. Ki-67 immunohistochemistry has a sensitivity of 74%, specificity of 86% and positive predictive value of 94% in detecting MM. hTERT immunohistochemistry detected MM with sensitivity and specificity of 68%. CONCLUSION: As a result, being cheap and simple methods, Ki-67 and hTERT immunohistochemistries can be used in differentiating malignant and benign mesothelial lesions in routine formalin-fixed, paraffin-embedded material.

Adult↗

PubMed1997

Changes in the population of proliferating cells in chicken anterior pituitary during induced molting: an immunocytochemical analysis for proliferating cell nuclear antigen.

The goal of this study was to determine whether cell proliferation is increased in the anterior pituitary during an induced molting period in chickens. The anterior pituitaries were collected from: 1) laying hens before initiation of an induced molt (control hens), 2) molting hens 2 to 16 d after cessation of lay, and 3) second cycle laying hens 1 d after returning to lay. Pituitary cephalic and caudal lobes were processed for immunocytochemistry of proliferating cell nuclear antigen (PCNA), and positive cells were counted by an image analyzer using light microscopy. In cephalic and caudal lobes, a small number of positive cells were observed in controls and molting hens 2 d after cessation of lay. The frequency of PCNA-positive cells started to increase from 7 d after cessation of lay (3 d after refeeding), and a significantly higher frequency of positive cells was observed in both lobes of molting hens 13 d after cessation of lay when compared to control hens, molting hens 2 d after cessation of egg lay, and second cycle laying hens. The frequency of PCNA-positive cells in second cycle laying hens decreased to a similar level to that of control hens. These results suggest that anterior pituitary tissue may be remodeled partially by a proliferation of cells during induced molting in hens.

Animals↗

PubMed2003

Cell proliferation and apoptosis are altered in mice deficient in the NF-kappaB p50 subunit after treatment with the peroxisome proliferator ciprofibrate.

We previously showed that the peroxisome proliferator ciprofibrate increases hepatic NF-kappaB DNA binding activity in rats, mice, and hepatoma cell lines. Here, we analyzed the response to ciprofibrate in mice that lack the NF-kappaB p50 gene (p50-/-). Wild-type and p50-/- mice were fed a diet with or without 0.01% ciprofibrate for 10 days. NF-kappaB DNA binding activity was present and increased after ciprofibrate treatment in wild-type mice, but was not detected in p50-/- mice. The untreated p50-/- mice had a higher level of hepatic cell proliferation, as measured by BrdU labeling, than did untreated wild-type mice. However, the increase in proliferation was greater in ciprofibrate-fed wild-type mice than in ciprofibrate-fed p50-/- mice. The apoptotic index was low in wild-type mice in the presence or absence of ciprofibrate. Apoptosis was increased in untreated p50-/- mice compared to wild-type mice; apoptosis was reduced in p50-/- mice after ciprofibrate feeding. The c-Jun and JunB mRNA levels were higher in untreated p50-/- mice than in untreated control mice; c-Jun mRNA levels increased, whereas JunB mRNA levels decreased in both groups after ciprofibrate treatment. The c-Jun and JunB protein levels were the same in untreated wild-type and p50-/- mice and increased in both groups after ciprofibrate treatment. Several apoptosis-related mRNAs were higher in untreated p50-/- mice compared to untreated control mice; expression of these genes increased in both groups after ciprofibrate treatment. These data indicate that NF-kappaB contributes to the proliferative and apoptotic changes that occur in the liver in response to ciprofibrate.

Administration, Oral↗

PubMed2005

Peroxisome proliferator-activated receptor gamma down-regulates receptor for advanced glycation end products and inhibits smooth muscle cell proliferation in a diabetic and nondiabetic rat carotid artery injury model.

Diabetes is associated with an increase in circulating advanced glycosylation end products (AGEs) and the increased expression of the receptor for AGEs (RAGE). Inhibition of AGE/RAGE binding through the administration of soluble RAGE (sRAGE) has been shown to decrease neointimal hyperplasia. Peroxisome proliferator-activated receptor gamma (PPARgamma), which inhibits neointimal hyperplasia, has been shown to decrease RAGE expression in cultured endothelial cells. We hypothesized that PPARgamma agonists inhibit neointimal hyperplasia via down-regulation of RAGE in vivo. Pretreatment of rat aortic smooth muscle cells (SMCs) with PPARgamma agonist rosiglitazone significantly down-regulated RAGE expression and inhibited SMC proliferation in response to the RAGE agonist S100/calgranulins. In vivo studies showed that rosiglitazone decreased RAGE expression and SMC proliferation at 7 days following carotid arterial injury in both diabetic and nondiabetic rats. At 21 days following injury, neointimal formation was significantly decreased in both diabetic and nondiabetic animals that received rosiglitazone. To determine whether inhibition of neointimal formation by PPARgamma activation could fully be accounted for by its down-regulation of RAGE, we compared the results obtained in animals treated with sRAGE, PPARgamma activator, and sRAGE + PPARgamma activator. Consistent with PPARgamma working through its effects on RAGE, we found that the addition of PPARgamma activator to sRAGE did not result in any further decrease in neointimal formation. These data demonstrate for the first time that PPARgamma agonists inhibit RAGE expression at sites of arterial injury and suggest that down-regulation of RAGE by the PPARgamma activation inhibits neointimal formation in response to arterial injury.

Animals↗

PubMed1993

Evaluation of proliferating cell nuclear antigen (PCNA) as an endogenous marker of cell proliferation in rat liver: a dual-stain comparison with 5-bromo-2'-deoxyuridine.

Proliferating cell nuclear antigen (PCNA) was evaluated as a marker of cell proliferation in formalin-fixed rat liver tissue through a comparative study with the thymidine analogue 5-bromo-2'-deoxyuridine (BrdU). The comparison was conducted through the introduction of a dual immunohistochemical procedure that allows the simultaneous detection of the two antigens. The results of this study suggest that although statistically similar indexes for each can be achieved, what has been reported to be the "S-phase fraction" of PCNA-labeled nuclei is significantly different from the population of cells marked by BrdU. The data also suggest that the reason for this difference is that the "S-phase fraction" of PCNA-labeled nuclei is the population of cells in late G1- and early S-phases. BrdU, by comparison, is incorporated into cells only during DNA synthesis. Therefore, although BrdU and PCNA labeling techniques may both be effective for evaluating cell proliferation rates, it must be recognized that labeling indices derived from each are not entirely synonymous. The method presented here for the simultaneous labeling of PCNA and BrdU antigens may have utility in studies of cell cycle perturbations.

Animals↗

PubMed1993

Phenobarbital-induced hepatocellular proliferation: anti-bromodeoxyuridine and anti-proliferating cell nuclear antigen immunocytochemistry.

We report modifications to immunocytochemical detection procedures for proliferating cell nuclear antigen (PCNA) which permit its identification in liver samples previously fixed for BrdU immunocytochemistry. Both methods have been used for the assessment of phenobarbital-induced cell proliferation in rat liver. The difficulties associated with the hitherto unsuccessful application of PCNA immunocytochemical methods to tissues fixed in formalin for BrdU visualization were overcome by epitope unmasking with acid hydrolysis, extension of primary antiserum (PC10) incubation, and employment of streptavidin-ABC-HRP. BrdU delivery via osmotic minipumps for 48 hr before euthanasia, followed by fixation in cold formalin for 14 days, yielded reliable and reproducible hepatocellular labeling and a peak of cell proliferation in all lobes on Day 3 (i.e., labeling during Days 1-3) of dosing with 80 mg/kg/day phenobarbital. Labeling indices (LI) of both control and phenobarbital-treated liver were lower in the left and right median lobes as compared with the lateral lobes. In sections of the left lateral lobe from the same liver, PCNA immunocytochemistry revealed a peak of proliferative activity (about one third of the maximum LI generated by BrdU incorporation) on Day 1. These findings, together with the advantages and disadvantages of both techniques, are discussed in the context of their applications to different investigative requirements.

Animals↗

PubMed2005

Nuclear receptors as targets for drug development: peroxisome proliferator-activated receptor gamma in mast cells: its roles in proliferation and differentiation.

Mast cells are derived from stem cells in bone marrow and their proliferation and differentiation are regulated by stimulation of stem cell factor derived from fibroblasts and/or IL-3 from T lymphocytes. The peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily and ligand-activated transcription factors. It has been reported that PPARgamma is expressed in mast cells, but its roles remain uncertain. Since mast cells produce and release prostaglandin D(2), which is metabolized to 15-deoxy-Delta(12,14)-prostaglandin J(2), a candidate for the endogenous PPARgamma agonist, mast cells play roles in inflammation and immunological response via the PPARgamma pathway. We will mainly discuss the contribution of PPARgamma to the proliferation and functions in murine cultured bone marrow derived mast cells.

Animals↗

PubMed1993

Comparison of proliferating cell nuclear antigen to tritiated thymidine as a marker of proliferating hepatocytes in rats.

Proliferating cell nuclear antigen (PCNA), an endogenous nuclear protein, has recently been used to identify replicating cells. PCNA was compared to tritiated thymidine ([3H]-TdR), a reliable and accurate exogenous labeling agent, to ascertain if PCNA gives comparable results for quantitative cell proliferation. Male F344 rats were treated with a single dose of 500 mg/kg 4-acetylaminofluorene (4-AAF), a known liver mitogen. Rats (n = 5) were euthanized and necropsied at 6, 12, 18, 24, 36, 48, 96, or 192 hr after treatment. Two hours before necropsy, rats were pulsed-dosed with [3H]-TdR (2 mCi/kg body weight). Livers were sectioned, autoradiography performed, and labeling indexes (LI), a measurement of the percentage of S-phase hepatocytes, determined. One and a half years after the completion of this study, the archival paraffin blocks of the liver tissue were sectioned and stained for PCNA by an immunohistochemical procedure. Immunocytochemical staining patterns of proliferating cell nuclear antigen antigen expression permitted the recognition of G1, S, G2, M, and quiescent cells. PCNA LI, generated by scoring only cells exhibiting S-phase staining patterns, was compared to the pulse [3H]-TdR LI for each animal. Similar periportal staining patterns of S-phase nuclei were detected by both markers. The [3H]-TdR LI and the PCNA LI exhibited a peak at 24 hr of approximately the same magnitude. However, while the [3H]-TdR LI had returned to near baseline at the 48-hr time point, the PCNA LI remained elevated until the 96-hr time point. This sustained elevation of the PCNA index cannot be explained at this time.(ABSTRACT TRUNCATED AT 250 WORDS)

2-Acetylaminofluorene↗

PubMed1993

Proliferating cell nuclear antigen: a marker for hepatocellular proliferation in rodents.

Two different markers for quantitating cell proliferation were evaluated in livers of control and chemically treated mice and rats. Proliferating cell nuclear antigen (PCNA), an endogenous cell replication marker, and bromodeoxyuridine (BrdU), an exogenously administered DNA precursor label, were detected in formalin-fixed, paraffin-embedded tissues using immunohistochemical techniques. The percentage of cells in S phase (labeling indexes, LI) evaluated as PCNA- or BrdU-positive hepatocellular nuclei was compared in recut tissue sections from animals given BrdU by a single IP injection 2 hr before killing the animals. Ten-week-old male B6C3F1 mice and F344 rats were exposed to known mitogenic hepatocarcinogens, Wy-14,643 (WY) in the diet at 0.1% for 2 days or 1,4-dichlorobenzene (DCB) in corn oil by gavage for 2 days (600 mg/kg/day in mice; 300 mg/kg/day in rats). In mice, PCNA and BrdU hepatocyte LI were similar in control, WY-treated, and DCB-treated animals. In rats, PCNA and BrdU gave similar LI in controls and Wy-treated animals. Although PCNA LI was statistically lower than BrdU LI in DCB-treated rats, both PCNA and BrdU LI for DCB-treated rats was increased over LI in control rats. Different patterns of PCNA immunohistochemical staining, interpreted to represent different subpopulations of cells at various phases of the cell cycle, were quantitated using PCNA immunohistochemistry. The proliferating index (PI), defined as the percentage of cells in the cell cycle (G1 + S + G2 + M), was more sensitive than the LI (S phase only) in detecting a chemically induced cell proliferative response.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Toxicological and pathological applications of proliferating cell nuclear antigen (PCNA), a novel endogenous marker for cell proliferation.

A major stimulus to study cell proliferation, particularly in rodent carcinogenicity assays and human tumors, has been the belief that the quantification of this fundamental biological process will provide the toxicologist and pathologist with objective data allowing a better understanding of the mechanisms involved in the toxicity and/or carcinogenicity of certain compounds as well as guiding more effective management of patients afflicted with neoplasia. Among the markers used for cell proliferation measurement, PCNA has recently gained much attention and holds much promise as it is intricately involved in the cell replication processes. It not only could allow measurement of the replication rates without necessitating pretreatment of the animal/tissue in prospective studies, but also would allow retrospective assessment of the proliferative rates in archival tissues due to the conservation of this marker in fixed and paraffin-embedded tissues. Finally, knowledge of the function of PCNA in the cell cycle and its regulation by other factors may help us understand the advantages and limitations of PCNA as a cell proliferation marker in its application in toxicology and as a prognostic marker in human tumors.

Animals↗

PubMed2004

Homeostatic proliferation of a Qa-1b-restricted T cell: a distinction between the ligands required for positive selection and for proliferation in lymphopenic hosts.

Naive T cells proliferate in response to self MHC molecules after transfer into lymphopenic hosts, a process that has been termed homeostatic proliferation (HP). Previous studies have demonstrated that HP is driven by low level signaling induced by interactions with the same MHC molecules responsible for positive selection in the thymus. Little is known about the homeostatic regulation of T cells specific for class Ib molecules, including Qa-1 and H2-M3, though it has been suggested that their capacity to undergo homeostatic expansion may be inherently limited. In this study, we demonstrate that naive 6C5 TCR transgenic T cells with specificity for Qa-1(b) have a capacity similar to conventional T cells to undergo HP after transfer into sublethally irradiated mice. Proliferation was largely dependent on the expression of beta(2)-microglobulin, and experiments with congenic recipients expressing Qa-1(a) instead of Qa-1(b) demonstrated that HP is specifically driven by Qa-1(b) and not through cross-recognition of classical class I molecules. Thus, the same MHC molecule that mediates positive selection of 6C5 T cells is also required for HP. Homeostatic expansion, like positive selection, occurs in the absence of a Qa-1 determinant modifier, the dominant self-peptide bound to Qa-1 molecules. However, experiments with TAP(-/-) recipients demonstrate a clear distinction between the ligand requirements for thymic selection and HP. Positive selection of 6C5 T cells is dependent on TAP function, thus selection is presumably mediated by TAP-dependent peptides. By contrast, HP occurs in TAP(-/-) recipients, providing an example where the ligand requirements for HP are less stringent than for thymic selection.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMedDate not supplied

A new cell proliferating marker: cytosolic thymidine kinase as compared to proliferating cell nuclear antigen in patients with colorectal carcinoma.

BACKGROUND: Proliferation markers are necessary for reliable diagnosis. Here we have presented for the first time thymidine kinase 1 (TK1) as a proliferative tumor marker for colorectal carcinoma. PATIENTS AND METHODS: Expression of TK1 in 54 colorectal lesions and 20 colorectal adenoma lesions was detected by immunohistochemistry technique (ABC). Proliferating Cell Nuclear Antigen (PCNA) was run in parallel. RESULTS: TK1-Labelling Index (LI) (65%) was higher than PCNA-LI (52%) in the malignant lesions, although not significantly different (p = 0.1717) between them. TK1-LI as well as PCNA-LI showed significant differences between colorectal carcinoma and colorectal adenoma (TK1 p = 0.0005, PCNA p = 0.0005). Both TK1-LI and PCNA were significantly different in respect to tumor stages (TK1 p = 0.0002, PCNA p = 0.0284). However, only TK1-LI showed significant difference in respect to tumor grades (p = 0.014), but not PCNA-LI (p = 0.132). CONCLUSION: TK1-LI showed more potential as a proliferating marker in colorectal carcinoma than PCNA-LI, especially for evaluating high-risk tumor grade and advanced stage in colorectal carcinoma.

Adenocarcinoma, Papillary↗

PubMed2001

Evaluation of germ-cell kinetics in infertile patients with proliferating cell nuclear antigen proliferating index.

AIM: To explore the usefulness of proliferating cell nuclear antigen proliferating index (PCNA PI) in the pathological diagnosis and treatment of male infertility. METHODS: Testicular biopsy specimen obtained from 48 cases of male infertility and 2 normal controls were fixed and embedded. The sections were stained with anti-PCNA monoclonal antibodies or haematoxylin/eosin. Proliferating index (PI), expressed as the percentage of germ-cell nuclei positively stained with PCNA antibody, was assessed from more than 20 seminiferous tubules or 600 germ-cells. RESULTS: The infertile patients were divided into 4 groups: Group 1, normal spermatogenesis (14 cases); Group 2, hypospermatogenesis (16 cases); Group 3, germinal arrest (10 cases); Group 4, Sertoli cell only syndrome (8 cases). The PCNA PI of normal control testis was 86.5% (mean value). Group 3 had a significantly lower PCNA PI (29.8%) than normal testis; Group 1 and 2 had similar PIs (82.3% and 82.3%, respectively) as the control testis. PI of the negative control (Group 4) was 0 as no germ-cells were found. CONCLUSION: PCNA PI is useful for assessing germ-cell kinetics, especially for pathological diagnosis of germinal arrest which is difficult to differentiate by routine HE staining technique. In germinal arrest, there is a significantly lowered PCNA PI, which is an indication of DNA synthesis deterioration, suggesting the use of therapies be different from those for hypospermatogenesis.

Adult↗