The human telomerase reverse transcriptase (hTERT) is an essential component of the holoenzyme complex that adds telomeric repeats to the ends of chromosomes. The hTERT transcript has been shown to have two deletion type alternative splicing sites. One deletion site induces the alpha-deletion variant, lacking 36 bp from exon 6, and the other induces the beta-deletion variant, lacking 182 bp from exons 7 and 8. Here, we identified a novel deletion variant of the hTERT transcript in hepatocellular carcinoma cell lines. The deleted transcript was characterized by an in-frame deletion of 189 bp, spanning nucleotides 2710 to 2898, corresponding to the complete loss of exon 11 (gamma-deletion). The region lacking in the gamma-deletion lies within RT motifs D and E, suggesting that it is missing conserved residues from the catalytic core of the protein. Both gamma- and alpha-deletion variants were occasionally detected, but the beta-deletion variant was frequently observed. Our results may provide important information for more detailed studies on the regulation of telomerase activity.

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hepatic metastasis in their resected liver have shown recurIt is well known that a urokinase-type plasminogen rence within 3 years, 9 prompting us to seek a new predictor activator receptor (uPAR) is a key protein in the plasfor this recurrence. minogen activation system, which plays a proteolyti-The metastatic process in malignant tumors involves local cally important role in the invasion and metastasis of invasion, intravasation, and extravasation. 10 These events various cancer cells. To assess the expression of uPAR depend on the tumor-associated proteolytic process including in hepatocellular carcinoma (HCC), we analyzed the exthe plasminogen activation system, and many reports have pression of uPAR messenger RNA (mRNA) and the proshown that the urokinase-type plasminogen activator (uPA) tein in 31 pair-samples of solitary HCC and nontumorous plays an important role in this process. 11-13 uPA is released liver tissues from the same patients. Fifteen samples exfrom tumor and stromal cells [14][15][16] in a single-chain zymogen hibited no histological potential of recurrence, such as form, pro-uPA. 17,18 pro-uPA is converted into a two-chain acportal involvement or intrahepatic metastasis (group A), tive form of uPA, which converts the ubiquitous zymogen and 16 samples exhibited such histological features plasminogen into the proteolytically active form, plasmin. (group B). Seventy-one percent of the cases showedPlasmin by itself degrades the extracellular matrix and actiuPAR signals, and these signals were mainly localized vates collagenases. 19 Some authors have described that poor at the cytoplasm of the tumor cells and tended to be at prognostic types of cancer cells show high levels of uPA. 20-22the front of invasive foci. 87.5% of the cases in group B The mechanism of the initial activation of pro-uPA under showed uPAR signals against 53.3% of the cases in group physiological conditions is unknown. uPA has a specific re-A (P õ .05). The rate of recurrence in the uPAR positive/ ceptor (uPAR) anchoring to the cell surface by glycosyl-phonegative cases in group A was 75.0% and 14.3%, respecphatidyl-inositol. [23][24][25][26][27] uPAR is a protein with an Mr55000-tively (P õ .05). In non-neoplastic cases, e.g., chronic ac-60000 (55-60 Kd molecular weight of uPAR antigen), tive hepatitis and cirrhosis, weak uPAR mRNA and protranslated from a 1.4-kb messenger RNA (mRNA) 28 and its tein signals were detected in hepatocytes neighboring amino-terminal domain has a high affinity with an epidermal the portal tracts, suggesting that this protein plays some growth factor-like domain in the pro-uPA and uPA molerole in such cases. The present study indicates that cules. 29,30 uPAR synthesis is regulated by growth factors such uPAR plays an important role at least in its initial stage as transforming growth factors b 1 and b 2 , epidermal growth in invasion and metastasis of HCC, and that uPAR exfactor, 31,32 and phorbol 12-myristate 13-acetate. 33 Binding of pression can be a candidate predictor of these factors.pro...

Urokinase-type plasminogen activator activity may be the most sensitive factor affecting HCC invasion in the plasminogen activation system and a strong predictor for the recurrence of HCC. We suggest that cases with uPA activity of more than 0.70 ng/mL should be carefully followed up for possible HCC recurrence.

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The transcystic decompression tube is easily and safely inserted with the J-kit. Among several strategies currently available for the management of choledocholithiasis, laparoscopic choledochotomy with the use of the J-tube is one of the safest and most feasible methods.

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