S-Phase cells in diseased human liver determined by an in Vitro BrdU-anti-BrdU method

Shimizu, Akio; Tarao, Kazuo; Takemiya, Shouji; Harada, Masaoki; Inoue, Tohru; Ono, Tetsuo

doi:10.1002/hep.1840080611

Cited by 33 publications

(2 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Because normal hepatocytes are considered to rarely replicate, 23 telomere length in the liver may be longer than that in PBL at the same age. Estimated average net telomere length in PBL at 60 years of age is calculated as 4,200 bp by assuming the information described above: (9,000-3,000 bp) Ϫ (45 bp/year) ϫ (40 years).…”

Section: Discussionmentioning

confidence: 99%

Reduction of telomeric repeats as a possible predictor for development of hepatocellular carcinoma: Convenient evaluation by slot-blot analysis

et al. 1999

View full text Add to dashboard Cite

Hepatocellular carcinoma (HCC) is one of the most prevalent cancers in the world, and hepatitis B and C viruses are the main causative agents for high incidence of HCC. 1 Although the mechanisms underlying HCC development have been widely investigated from both points of direct and indirect effects of the viruses, 2 they are still open to debate. Whatever the mechanisms involved, these viral infections are correlated with a slow, long-lasting disease that is a definite risk for neoplastic degeneration.Telomeres are composed of tandem arrays of a short DNA sequence, d(TTAGGG)n in vertebrates, and associated proteins. They are essential genetic elements and stabilize the natural ends of linear eukaryotic chromosomes. 3 The endreplication problem, the inability of DNA polymerases to completely replicate the end of a DNA duplex, 4 results in telomere shortening in proportion to cell replication. 5 Because severity of persistent hepatocellular degeneration might indicate a risk for HCC development, an extent of telomere erosion has a possibility to be a predictor for HCC development in the liver under chronic inflammation.The standard and currently most reliable method for evaluating telomere length uses Southern analysis of terminal restriction fragment (TRF) lengths. 6 TRFs, however, contain DNA other than uniform telomeric repeats, 7 and the analysis requires several micrograms of high-molecular-weight genomic DNAs. In addition, telomere length varies among individuals prior to replicative histories. 8 Although this variation should be normalized before comparison of telomere length among patients, all previous reports describing telomere alteration in chronic liver diseases were unfortunately evaluated without any standardization. 9-12 These technical limitations inherent in the complexity of TRF make it difficult to analyze telomere dynamics using clinical materials, especially in the case that only a small specimen is available.In this study, we first evaluated reliability and reproducibility of a slot-blot analysis to detect alteration of telomeric repeats content. Next, we determined the content in various liver tissues. For comparison of the content in the liver with respect to chronic inflammation, we standardized the content

show abstract

Section: Discussionmentioning

confidence: 99%

Reduction of telomeric repeats as a possible predictor for development of hepatocellular carcinoma: Convenient evaluation by slot-blot analysis

et al. 1999

View full text Add to dashboard Cite

show abstract

“…PCNA-positive hepatocytes were generally distributed throughout the nodule, and the values of PCNA-LI in cirrhosis are close to those found in the literature for both PCNA-LI (1.28%-17%) and BrdU-LI (1.2%-4.1%). 17,20,[25][26][27][28][29][36][37][38][39][40][41][42][43] This work further analyzes the relationship between hepatocyte proliferation and liver functional reserve in cirrhotic patients and shows that the PCNA-LI value declines with worsening Child class and is closely associated with serum albumin, a marker of protein synthesis in the liver, whatever the cause of the disease. The impact of the alcoholic origin of cirrhosis on the PCNA-LI value as well as on the prognosis of patients was not proved to be significant in our study.…”

Section: Discussionmentioning

confidence: 99%

Relationship between hepatocyte proliferative activity and liver functional reserve in human cirrhosis

et al. 1996

View full text Add to dashboard Cite

tients and decreases with worsening of the disease. Hepatocyte proliferative activity is elevated in cir-(HEPATOLOGY 1996;23:1003-1011.) rhotic patients who develop hepatocellular carcinoma (HCC) and decreased in alcohol-induced hepatitis patients with poor outcome. Hepatocyte proliferative activity has not been evaluated in an unselected populaProliferating cell nuclear antigen (PCNA) is a highly tion of cirrhotic patients regarding the severity of the conserved acidic nuclear protein with an apparent modisease. Forty-six cirrhotic patients (21 alcoholic, 20 vi-lecular weight of about 36 kd. It is synthesized in the ral, and 5 other) were prospectively analyzed by prolifer-late G 1 and in the S-phase of the cell cycle, 1-3 and it ating cell nuclear antigen (PCNA) immunostaining on has been identified as the auxiliary protein of DNA methanol-fixed, paraffin-embedded liver biopsy speci-polymerase-d. one-which represents PCNA tightly associated withIt declined with worsening Child-Pugh score: 9.15% (range, 3.3%-20.2%), 5.3% (range, 1.2%-18%), and 2.4% DNA replication sites-appears to be maintained in (range, 0%-4.4%) in Child classes A, B, and C, respectively cells or in tissues after methanol fixation. 5,6 Accord-(P õ .05). Using the best cutoff PCNA-LI value to divide ingly, PCNA immunopositivity after methanol fixation cirrhosis into slowly and rapidly proliferating tissue marks only that fraction of the cell population that is subsets, the PCNA index was independently associated undergoing DNA synthesis (S-phase), whereas, with with serum albumin. The probability of survival in pa-formalin fixation, the staining of nuclei extends to G 1 , tients with a high PCNA-LI (ú4.4%) was significantly G 2 , and M phases. there was a good concordance between PCNA immunopatic portosystemic shunt (TIPS), the PCNA-LI decreased after the procedure. This early impairment of staining and the other well-established parameters of hepatocyte proliferative activity after TIPS placement cell proliferation such as thymidine 6,10 or bromodeoxymight reflect the functional alterations induced by this uridine (BrdU) 7,11 incorporation, S-phase fraction detreatment. In conclusion, hepatocyte proliferative activ-termined by flow cytometry, 12-14 Ki-67 immunoreactivity assessed by PCNA-LI is increased in cirrhotic pa-ity, 15,16 and DNA polymerase-a immunopositivity. 17 Moreover, in methanol-fixed tissue treated with the BrdU/PCNA double-labeling procedure, the proportion copy. 18 From the

show abstract

An analysis of proliferating cells in biopsy specimens from patients with small hepatocellular carcinoma

Seki¹,

Sakaguchi²,

Kawakita³

et al. 1992

Cancer

View full text Add to dashboard Cite

The proliferation of neoplastic and nonneoplastic heap‐tocytes is caused by various humoral growth factors with autocrine and paracrine mechanisms, and the proliferative activity of both hepatocytes and nonhepatocytic cells contributes to neoplastic growth. The authors attempted to detect various kinds of proliferating cells immunohis‐tochemically in small hepatocellular carcinoma (HCC) using a monoclonal antibody against DNA polymerase alpha. Most of the HCC cells that stained for this enzyme were small, had basophilic cytoplasm with poorly developed organelles, and aggregated to form clusters distributed randomly within cancer nests. Nonhepatocytic cells also were stained, including some endothelial cells, Kupffer's cells, macrophages, and lymphocytes. Fat‐storing cells were not stained. The number of stained sinusoidal (capillary) cells decreased in this order: Kupffer's cells and macrophages, endothelial cells, and fat‐storing cells. Nonhepatocytic cells, including lymphocytes, proliferated more actively in areas with actively growing HCC cells than in those with quiescent cancer cells. The relationship between stained HCC cells and stained sinusoidal cells was clearly defined; the correlation coefficient was 0.97. These findings suggest the possibility of a relationship between the proliferative activity of neoplastic hepatocytes and that of sinusoidal cells, including lymphocytes. Cancer 1992; 69:2433‐4439.

show abstract

S-Phase cells in diseased human liver determined by an in Vitro BrdU-anti-BrdU method

Cited by 33 publications

References 9 publications

Reduction of telomeric repeats as a possible predictor for development of hepatocellular carcinoma: Convenient evaluation by slot-blot analysis

Reduction of telomeric repeats as a possible predictor for development of hepatocellular carcinoma: Convenient evaluation by slot-blot analysis

Relationship between hepatocyte proliferative activity and liver functional reserve in human cirrhosis

An analysis of proliferating cells in biopsy specimens from patients with small hepatocellular carcinoma

Contact Info

Product

Resources

About