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PubMed1998

Telomerase activity and alterations in telomere length in human brain tumors.

Telomerase activity was examined in 170 human brain tumor tissues, and terminal restriction fragment (TRF) length was examined in 152 of the 170. Telomerase activity was detected in 61.7% (66 of 107) of the neuroepithelial tumors. However, the detection rates of telomerase activity were widely different for different histopathological entities. In the case of astrocytic tumors, the detection rate was 20.0% (3 of 15) for grade II astrocytomas, 40.0% (6 of 15) for anaplastic astrocytomas, and 72.3% (34 of 47) for glioblastomas. The mean TRF length of the tumors with telomerase activity was significantly shorter than that of the tumors with undetectable telomerase activity for each tumor entity. In grade II and anaplastic astrocytomas, telomerase activity was an indicator of early histological progression and reduced survival of the patients, although there was no difference in MIB-1 staining indices between the tumors with and without telomerase activity at onset. In three astrocytic tumors, concurrence of telomere shortening and telomerase reactivation was observed at recurrence; in these cases, tumors progressed to a higher grade. Ten glioblastomas that progressed from lower-grade tumors exhibited telomerase activity, and their TRF lengths were reduced in 80% (8 of 10). In contrast, telomerase activity was detected in only 63.3% (19 of 30; P < 0.05) and the TRF length remained compatible with normal values in 56.7% (17 of 30; P < 0.01) of de novo glioblastomas. Thus, telomerase activity strongly correlated with potential tumor progression in the short term as well as with progression itself of the astrocytic tumors, whereas telomeres may still have been in the process of shortening in some of the de novo glioblastomas. High telomerase activity was exhibited in all primitive neuroectodermal tumors, anaplastic oligoastrocytomas, neuroblastomas, and oligodendrogliomas. TRF length was reduced in the majority (14 of 15) of three previously high-grade tumors, whereas it was compatible with that of normal brain tissues in the oligodendrogliomas, suggesting that telomerase activity with shortened telomeres correlates with the aggressive growth of high-grade neuroepithelial tumors. Tumor cell lines could be established from 17.2% (5 of 29) of neuroepithelial tumors with telomerase activity but not from tumors without this activity (P < 0.05), suggesting that telomerase reactivation is an essential event in the neuroepithelial cell immortalization in vitro. In nonneuroepithelial tumors, telomerase activity was detected in malignant tumors, such as germ cell tumors, lymphomas, metastatic adenocarcinomas, hemangiopericytomas, and an anaplastic meningioma. In contrast, such activity was not detected in benign tumors, including meningiomas, pituitary adenomas, hemangioblastomas and schwannomas, except for one hemangioblastoma that recurred four times and displayed malignant features at the fourth recurrence. These findings suggest that telomerase activity can be an index of malignant potential or malignancy itself in nonneuroepithelial brain tumors.

Adolescent↗
PubMed1998

[Telomere length and telomerase activity in hepatocellular carcinoma].

Telomerase activity and terminal restriction fragment (TRF) length were examined in hepatocellular carcinoma (HCC). Telomerase activity was assayed by telomeric repeat amplification protocol (TRAP) connected with an internal telomerase assay standard (ITAS). The incidence of strong telomerase activity (highly variable level compared with the activity of non-cancerous liver tissue) was 79% in well, 84% in moderately, and 100% in poorly differentiated HCC, while 0% in non-cancerous liver tissues. The incidence of TRF length alteration (reduction or elongation) was 53% in HCC. The incidence of TRF alteration was significantly higher in HCC exceeding 3 cm in diameter, moderately or poorly differentiated in histology. Telomerase activity was not associated with TRF length alteration in HCC. In conclusion, strong telomerase activity and TRF length alteration increased with HCC tumor progressions.

Carcinoma, Hepatocellular↗
PubMed1985

Antigen-nonspecific T cell-derived factors in B cell activation: differences in the requirements for interleukin 2 in responses of unprimed and primed B cells.

The requirements for interleukin 2 (IL2) and other T cell-derived helper factors in the responses of unprimed and antigen-primed B cells to sheep erythrocytes were investigated. Unprimed B cells required both IL2 and additional factor(s), hereafter referred to as T cell-replacing factor (TRF), in addition to specific antigen, for antibody production. IL2 was required only during the early stages (approximately equal to 24 h) of culture while TRF was necessary only after this time and was then required throughout the remaining culture period. IL2 stimulated the appearance of Thy-1+ cells in unprimed "B cell" populations which could substitute for the function of IL2, implicating an indirect role, at least in part, for IL2 in the TRF assay. Furthermore, in contrast to the results with unprimed B cells, primed B cells required only late-acting TRF for optimal antibody responses. We suggest that IL2 activates residual T cells or precursors of T cells in B cell populations which then function, in the presence of specific antigen, to render B cells receptive to T cell-derived factors which promote B cell growth and differentiation.

Animals↗
PubMed1987

Analysis of T cell-replacing factor-like activity: potent induction of T helper activity for human B cells by residual concanavalin A and interleukin 2.

At least two factors with the capacity to induce IgM synthesis in human B cells were found to be present in the 15-20-kDa fraction of the supernatant of mononuclear cells activated with concanavalin A (Con A) and phorbol ester. Previously, it has been shown (Sauerwein, R. W. et al., Eur. J. Immunol. 1985. 15: 611) that interleukin 2 (IL2) in this material is able to induce T cell-dependent IgM secretion in normal B cells. Evidence was obtained for the presence of another factor distinct from IL2 that could replace T cells in the induction of B cell differentiation. We have analyzed this factor with the use of a neoplastic B cell population of prolymphocytic origin that was functionally nonresponsive to IL2. T cell-replacing factor (TRF)-like activity and IL2 could be separated by ion-exchange chromatography, although a small amount of IL2 was recovered in the TRF fractions. This small amount of IL2 was found to be crucial for the observed TRF activity. Moreover, a substantial amount of monomeric Con A was detected in the TRF preparation. Our studies show that Con A in the presence of IL2 can act as a potent inducer of helper function in lower numbers of T cells for normal and neoplastic B cells. Functional assays for T cell contamination in B cell suspensions are therefore of limited value because they are determined by the efficiency of the stimulating signal. Particularly in those B cell factor preparations, obtained from mitogen-activated T cells with an obligatory or unidentified role of IL2, the possible effect of a contaminating mitogen must be considered.

Antibody Formation↗
PubMed1988

Interleukin 2 and low molecular weight B cell growth factor are T cell-replacing factors for different subpopulations of human B cells.

Both recombinant human interleukin 2 (rhIL 2) and low molecular weight B cell growth factor (BCGFlow) were shown to be T cell-replacing factors (TRF) in specific antibody responses to influenza virus by human blood and tonsillar B cells. When B cells were separated into high and low-density populations on Percoll gradients at 1.074 kg/l, IL 2 was found to act as a TRF only on the low-density B cells, whereas BCGFlow was a TRF for high-density B cells with a lesser effect on low-density B cells. Both populations of B cells responded well in the presence of T cells. The high-density B cells could not be activated to respond to IL 2 by either IL 1, rhIL 4 or by a CD22 monoclonal antibody known to enhance B cell activation. In contrast, a 24-h preincubation with T cells and antigen appeared to prime high-density B cells to respond to IL 2. These results show that high-density B cells can in fact respond to TRF, and that IL 2 and BCGFlow act on different populations of B cells which may be defined by prior exposure to T cells.

B-Lymphocytes↗
PubMed2007

Effect of glycosylation on the protein pattern in 2-D-gel electrophoresis.

Single proteins, when analyzed with 2-D-PAGE, often show multiple spots due to PTMs. In gels of human body fluids, the spot patterns facilitate the assignment and identification of the proteins. We analyzed serums from patients with congenital disorders of glycosylation (CDG) in which glycoproteins are strongly impacted and exhibit highly distinguishable spot patterns compared to healthy controls. We detected a typical protein pattern for alpha1-acid glycoprotein (AGP) and transferrin (Trf) that are markers for CDG. AGP contains five glycosylation sites which results in a complex microheterogeneity of the glycoprotein. On the other hand, in Trf, a glycoprotein with only two glycosylation sites, mainly biantennary complex-type-N-linked glycans are bound. We used 2-D-PAGE, MALDI-TOF-MS, and ESI-MS for the analysis of these glycoproteins and their corresponding glycans. In AGP, the heterogenic glycosylation of the different glycosylation sites is responsible for the complex spot pattern. In contrast to AGP, the protein spots of Trf cannot be explained by glycosylation. We found strong evidence that oxidation of cysteine is responsible for the spot pattern. This study contradicts the commonly accepted assumption that the multiple protein spots of Trf observed in 2-D-PAGE are due, as in AGP, to the glycosylation of the protein.

Carbohydrate Metabolism, Inborn Errors↗
PubMed1999

Isolation of cDNA, chromosome mapping, and expression of the human TBP-like protein.

TBP is an essential factor for eukaryotic transcription. In this study, we identified a human cDNA encoding 21-kDa TBP-like protein (TLP). The TLP ORF, carrying 186 amino acids, covered the entire 180 amino acids of the C-terminal conserved domain of human TBP with 39% identity and 76% similarity. FISH determined that human tlp gene was located at chromosome 6 region q22.1-22.3. Northern blot analysis demonstrated that TLP mRNAs were expressed in various human tissues ubiquitously. We found that the TLP proteins exist in multiple mammalian cells and chicken cells. Although the Drosophila TBP-related factor (TRF) is a neurogenesis-related transcription factor, expression of TLP was nearly constant throughout the neural differentiation of P19 cells. Unlike TRF, TLP did not bind to the TATA-box nor direct transcription initiation in vitro. Similarity between TRF and TLP was considerably lower (35 in alignment score) than that between Drosophila TBP and human TBP (88 in alignment score). Multiple amino acids critical for the TBP function were deleted or substituted in TLP. We suggest that TLP is not a bona fide vertebrate counterpart nor a direct descendant of TRF.

Amino Acid Sequence↗
PubMed1995

Evidence for a critical telomere length in senescent human fibroblasts.

Telomeres, the G/C-rich DNA sequences capping the ends of all eukaryotic chromosomes, have been shown to shorten during replicative aging of normal cells in vitro and in vivo. Moreover, variation in the initial length of terminal restriction fragments (TRF) accounts for much of the variation in replicative capacity of fibroblast cultures from different donors. Since replicative capacity also varies significantly between clones in a mass culture of fibroblasts from a single donor, we wished to further test the hypothesis that the shortening of telomeres to a critical or threshold length acts as a signal for cell senescence. Thus, we measured TRF length and total telomeric signal intensity for 35 clonal fibroblast populations at early passage and at senescence. Replicative capacity was found to be directly proportional to mean TRF length (m = 7.2 population doublings/kbp, r = 0.65, P = 0.0004) and total signal intensity (m = 25.0 population doublings/unit, r = 0.63, P < 0.003) at early passage. More importantly, the variability in both mean TRF length and signal intensity (F = 2.0 and 2.9; P = 0.02 and 0.03, respectively) at senescence was markedly less than that at early passage. Although initial telomere length cannot account for all of the interclonal variability in replicative capacity, our observations support the existence of a critical telomere length in senescing cells and a causal role of telomere shortening in cell senescence.

Adult↗
PubMed1994

Differential predictive value of parents' and teachers' reports of children's problem behaviors: a longitudinal study.

This study investigated the prediction of signs of disturbance in 946 children originally aged 4 to 11 years from the general population across a 6-year period. Parents' and teachers' ratings obtained via the Child Behavior Checklist (CBCL) and Teacher's Report Form (TRF) were tested as predictors of (a) academic problems, (b) school behavior problems, (c) receipt of mental health services, (d) child's need for professional help, (e) suicidal behavior, and (f) police contacts. Total problem scores in the deviant range on the CBCL or TRF were significantly associated with poor outcomes 6 years later. The combination of deviant scores on both the CBCL and TRF was a powerful predictor of poor outcomes with 56% of the girls, and 36% of the boys with total problem scores in the deviant range on both instruments maladjusted 6 years later. The CBCL syndromes Attention Problems and Delinquent Behavior, and the TRF syndromes Delinquent Behavior, Somatic Complaints, and Social Problems significantly predicted poor outcomes. Teachers' reports predicted poor outcomes equally well or even somewhat better than parents' reports. It is important to include teacher information in the diagnostic assessment of children.

Adolescent↗
PubMed2006

Preoperative enteral immunonutrition improves postoperative outcome in patients with gastrointestinal cancer.

OBJECTIVES: The purpose of this study was to evaluate the effect of preoperative immunonutrition pharmaceutics (IMPACT) diet versus standard enteral nutrition (EN) on the nutritional status and immunity of patients with colorectal or gastrointestinal (GI) cancer and to evaluate whether it influences the incidence of postoperative complication. METHODS: Sixty patients with GI cancer were randomly divided into 2 groups, immunonutrition (IM) and control diet (CT), each of which was fed with IMPACT and conventional diet, respectively, for 7 days before surgical procedures. Variables of nutritional status and immunity, postoperative complications, infections, and the days of postoperative hospitalization were measured. RESULTS: There were no significant differences in the immunological and nutritional variables between the 2 groups preoperatively. The incidence of postoperative complications was significantly lower and the days of postoperative hospitalization were significantly decreased in the IM group. Serum concentrations of both prealbumin (PALB) and transferrin (TRF) were lower in the IM than in the CT group on postoperative day 3 (P<0.01). TRF continued to be significantly lower in the CT group than in the IM group between day 4 and day 7. However, PALB was significantly lower than before operation in the IM group on postoperative day 3 and TRF was significantly higher in the IM than the CT group on postoperative day 3 (P<0.05). Both PALB and TRF were significantly higher in the IM than the CT group on postoperative day 7 (P<0.05). Postoperative immunoglobulin G (IgG) level in the IM group was higher than that in the CT group (13.35+/-2.06 g/l vs. 9.59+/-2.23 g/l, P<0.05). CD4/CD8 ratio was significantly higher in the IM group (2.10+/-0.51 vs. 1.62+/-0.52, P<0.05). CONCLUSIONS: Preoperative enteral IM in patients with GI cancer improves nutritional status and immunity and decreases the incidence of postoperative complications and infections.

Chi-Square Distribution↗
PubMed2006

Parent-teacher disagreement regarding behavioral and emotional problems in referred children is not a risk factor for poor outcome.

OBJECTIVE: To investigate whether parent-teacher disagreement regarding the presence of psychopathology predicts poor outcome in children who have been referred to mental health services METHODS: A total of 532 6- to 12-year-old children who had been referred to an outpatient department for child and adolescent psychiatry were followed up across an average period of 6.3 years. At initial assessment, standardized parent and teacher ratings of the child's psychopathology were obtained with the Child Behavior Checklist (CBCL) and Teacher's Report form (TRF). At follow-up, indices of poor outcome were assessed. RESULTS: Several CBCL and TRF scale scores predicted poor outcome. Discrepancies between CBCL and TRF scores were not useful as additional predictors. Some additive effects were found; future police/judicial contacts and disciplinary problems in school were predicted by CBCL and TRF scores. CONCLUSIONS: The findings underscored the need for information from different informants in clinical practice. However, discrepancies between parent and teacher ratings do not predict outcome, and should not alert clinicians.

Adolescent↗
PubMed1985

Nucleotide sequence of the genes involved in phosphate transport and regulation of the phosphate regulon in Escherichia coli.

The pstA(=phoT), pstB and phoU genes are situated at 84 minutes on the Escherichia coli genetic map. All of them are involved in the negative regulation of the phosphate regulon, and all of them except for phoU are required for the binding-protein-mediated, highly specific phosphate transport. We have determined the DNA sequence of about 4 X 10(3) bases of chromosomal segment containing these genes. Four translational reading frames (TRFs) were detected in the region. We attempted to assign the TRFs to the mutant alleles. Plasmids were constructed so that each contained only one of the TRFs, downstream from the lac promoter, to be used for the complementation tests. By this test, TRF-2, TRF-3 and TRF-4 were identified with the pstA(=phoT), pstB and phoU genes, respectively. Alkaline phosphatase-constitutive mutations of the two strains in our collection were complemented by the plasmid with the TRF-1 region. Therefore, we propose to designate the allele phoW. The order of the genes in this region has been established to be phoS-phoW-pstA(=phoT)-pstB-phoU counterclockwise on the E. coli genetic map.

Base Sequence↗
PubMed1988

Cell cycle-related proteins: a flow cytofluorometric study in human tumors.

We used 2-parameter flow cytometry (FCM) to investigate the relationship between the cell cycle phases and 3 proteins whose expression is known to increase in proliferating cells: the surface antigen transferrin receptor (Trf-r), the "cyclin" (a proliferating cell nuclear antigen, PCNA), and the nuclear antigen recognized by the monoclonal antibody (MoAb) Ki-67. FITC-labeled antibodies against Trf-r, PCNA, and the Ki-67-reactive antigen, as well as propidium iodide-DNA distribution, were simultaneously measured on human leukemia HL-60 and K562, and breast carcinoma MCF-7 cell lines and on fresh human leukemic and glioblastoma cells. The 70% ethanol fixation for Trf-r and PCNA and the 95% acetone fixation for Ki-67 plus permeabilization (with 0.1% and 1% Triton X100, respectively, for the surface and the nuclear antigens) produced cell suspensions with negligible cell clumping, high-quality DNA profiles, and bright specific immunofluorescent staining. The investigated proteins have different relationships with the proliferative state of the cell. Trf-r is expressed mainly at the transition from G0/G1 to S-phase. PCNA expression is prominent in late G1 and through S-phase and decreases in G2-M. The Ki-67-reactive antigen is widely distributed in G1, S, and G2-M phases. Knowledge regarding the relationships between proliferation-associated antigens and cell cycle phase in normal and neoplastic cells could improve our understanding of the mechanisms underlying growth regulation and neoplastic transformation. Bivariate FCM is an easy method for obtaining these data from large numbers of cells.

Antibodies, Monoclonal↗
PubMed1989

Influence of germ cells on Sertoli cell secretory activity in direct and indirect co-culture with Sertoli cells from rats of different ages.

We examined the effect of direct and indirect Sertoli-germ cell co-culture on androgen binding protein (ABP) and transferrin (TRF) secretion by Sertoli cells (Sc) from 10-, 18-, and 26-day-old rats. Addition of germ cells (Gc), mainly (greater than 80%) pachytene spermatocytes, directly to Sc monolayers enhanced basal and follicle-stimulating hormone (FSH) + testosterone-stimulated ABP and TRF secretion at all three ages. When the Gc were co-cultured indirectly with Sc (separated by a Nucleopore filter), only 50% of the direct stimulatory effect was found at 18- and 26-day-old groups, whereas no difference between direct and indirect co-culture was noted with Sc from 10-day-old rats. With 18- and 26-day-old rat Sc, the Gc effect on ABP and TRF secretion declined after 6 days of Sc culture, reaching the level of Sc-only cultures after 10 days, whereas the direct effect was maintained throughout the entire culture period. With Sc from 10-day-old animals, both direct and indirect effect of Gc decreased after 6 days but the levels of ABP and TRF secretion remained above those of Sc-only cultures. The viability and number of Gc in indirect co-cultures were maintained significantly higher than in Gc-only control cultures. The direct and indirect Gc effect was completely reversed 48 h after the Gc were removed from Sc cultures of 18- and 26-day-old rats, whereas in Sc cultures from 10-day-old rats 40% of the stimulatory effect remained after 48 h of Gc removal. We conclude that Gc can influence Sc secretory activity through both direct contact and some released factor(s). These two pathways may have different relevance at different ages during sexual maturation.

Aging↗
PubMed1996

Telomeric repeat fragment lengths are not correlated to histological grading in 85 breast cancers.

The mean telomeric repeat fragment (TRF) lengths of 85 breast cancer samples were determined. The TRF length varied between 7260 bp and 14570 bp (average 11370 bp) reflecting a unimodal distribution. There was no significant correlation between TRF length and the histological grade of the tumor. Neither were there differences in telomeric length between different histological types of tumors, in particular lobular and ductal types, nor correlations between TRF length and age of patient, tumor volume, lymph node status, or steroid receptor status. These results contradict the hypothesis that the telomere repeat fragment sizes represent limiting or promoting factors for the growth of breast cancer.

Breast Neoplasms↗
PubMed1995

Tocotrienols from palm oil as potent inhibitors of lipid peroxidation and protein oxidation in rat brain mitochondria.

The tocotrienol-rich-fraction (TRF) from palm oil, being tried as a more economical and efficient substitute for alpha-tocopherol, significantly inhibited oxidative damage in vitro to both lipids and proteins in rat brain mitochondria induced by ascorbate-Fe2+, the free radical initiator azobis(2-amidopropane)dihydrochloride (AAPH) and photosensitisation. The observed inhibitory effect was both time- and concentration-dependent. At a low concentration of 5 microM, TRF can significantly inhibit oxidative damage to both lipids and proteins. The inhibitory effect of TRF seems to be mainly due to gamma-tocotrienol and to a lesser extent alpha- and delta-tocotrienols. TRF was significantly more effective than alpha-tocopherol. This fraction from palm oil can be considered a natural antioxidant supplement capable of protecting the brain against oxidative damage and thereby from the ensuing adverse alterations.

Animals↗
PubMed2006

Radiocompetition of secretory pregnancy-associated glycoproteins as chorionic ligands with luteal and uterine gonadotrophin receptors of pregnant pigs.

Porcine pregnancy-associated glycoprotein (pPAG) family is very promiscuous and its role(s) remains unknown. The objective of this study was to identify whether secretory placental proteins (including pPAGs), produced in vitro by porcine chorionic explants, may interact with other proteins/targets, i.e. luteal and uterine binding sites of pregnant pigs. Trophoblast (TRF) and trophectoderm (TRD) were harvested during peri-implantation and placentation periods (14-61 dpc-day post coitum). In vitro-produced TRF/TRD proteins were isolated from media by ultrafractionation (>10 kDa MWCO) or precipitation with 20-75% saturation of (NH(4))(2)SO(4) and pPAG proteins were monitored by Western blotting. Secretory TRF/TRD ligands (including PAGs) were serially diluted (0.78-25 microg/ligand) and examined by radioreceptor assay (RRA). Luteal and uterine membrane receptors of pregnant pigs (pRc) were isolated from corpora lutea (pCLRc), myometrium (pMYORc) and endometrium (pENDRc). The three pRc types were harvested during three periods of pregnancy: 14 dpc (14 Rc), 21-26 dpc (21-26 Rc) and 31 dpc (31 Rc). The RRA competitions of individual TRF or TRD ligands were performed with (125)I-hCG as tracer and different pRc types. The RRA results of TRF/TRD were compared to hCG/pLH ligands--as positive controls (0.39-50 ng/ml), and endometrial (END) proteins (0.78-25 microg/ml) produced in vitro by END explants of cyclic, pseudopregnant and pregnant gilts (cEND, PsEND and pEND, respectively)--as negative control ligands. Results indicated that secretory TRF/TRD proteins (+pPAGs) were able to compete with (125)I-hCG for binding with other proteins/targets, i.e. luteal and uterine receptors of pregnant pigs (pCLRc, pMYORc and pENDRc) in a concentration- and pregnancy stage-dependent manner. This study indicated that porcine secretory 14-15 dpc TRF (pPAG; 30-73 kDa) ligands, effectively displaced (125)I-hCG tracer from pCL14Rc (up to P< or =0.01), corresponding to displacement by hCG and porcine LH. During the early stage of pregnancy, some competition tendency (P< or =0.01) was also detected for TRF ligands (14-15 dpc) with pEND14Rc. As pregnancy advanced, significant (125)I-hCG competition (at least P< or =0.05) with secretory semi-purified TRD ligands (30-42 dpc) was determined for all types of examined receptors pCL31Rc, pMYO31Rc and pEND31Rc, mainly with TRD fractions precipitated by 20% saturation of (NH(4))(2)SO(4). It seems that chorionic pPAG family can be involved in luteoprotective mechanism during implantation and placentation, according to the binding-interaction with luteal and uterine gonadotropin receptors of pregnant pigs.

Animals↗
PubMed2004

Correlation between telomerase expression and terminal restriction fragment length ratio in non-small cell lung cancer--an adjusted measurement and its clinical significance.

OBJECTIVE: To establish a new model for analyzing the correlation between the terminal restriction fragment (TRF) length and telomerase activity in non-small cell lung cancer (NSCLC) patients due to inconsistent results in previous reports. METHODS: Between January 1999 and December 1999, 79 NSCLC patients were studied. The activity of telomerase was measured by telomeric repeat amplification protocol, and the telomere restriction fragment (TRF) length was measured by Telomere Length Assay Kit and Southern blotting. The correlation between expression of telomerase activity and the TRF length ratio (TRFLR) using the tumor-to-normal TRFLR (t/n TRFLR) was examined. RESULTS: Positive telomerase activity was observed in 48 (60.8%) of the tumor tissue samples and in 5 (6.3%) of the normal tissue samples (P < 0.0001). The mean TRF lengths were 5.32+/-1.53 kb in normal tissue samples and 3.95+/-1.92 kb in tumor tissue samples, respectively (P = 0.0001). The 4-year cumulative survival rates of lower t/n TRFLR (< or = 75%) and higher t/n TRFLR (>75%) patients were 69.2 and 41.2%, respectively (P = 0.0227). Independent prognostic factors include t/n TRFLR (P = 0.014), T-status (P = 0.027), and N-status (P = 0.020) of the tumor. CONCLUSIONS: Our data suggest that there is a good correlation between the t/n TRFLR and expression of telomerase activity. A higher t/n TRFLR may indicate that the tumor regains its ability to repair the telomere lost and escapes the apoptosis scenario, which is subsequently reflected in poorer patient outcomes.

Adult↗