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Comparison of tumor histology, primary tumor size, lymph node metastasis, and tumor stage with telomerase activity in primary, resected non-small-cell lung cancer*
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Telomerase enzyme activity is not detected in most normal cells, a phenomenon believed to be associated with limitations on cellular proliferation. Since this activity is detected in nearly all human tumors, including non-small-cell lung cancers, it has been suggested that telomerase activation may be coupled to acquisition of the malignant phenoty...
Contexts in source publication
Context 1
... benign lung tissue adjacent to 34 of these NSCLC specimens was also examined. Ninety-eight patients with stage I-IIIA tumors and one patient with stage IV disease were treated by surgical resection alone (Table 1); six patients had preoperative chemotherapy. The patients were treated during the period from Janu- ary 1990 through May 1996, and clinical follow-up was updated as of September 1996. ...Context 2
... the histologic tumor type (P .87) ( Table 1). Patient age was correlated inversely with telomerase ac- tivity (r -.4; P<.01). ...Context 3
... activity was detected in 95.0% of T1, 80.3% of T2, and 92.3% of T3 tumors (Table 1). The average telom- erase activity (TPG) was 18 in T1 and T2 tumors compared with 36 in T3 tumors (P .03) ...Similar publications
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The proliferative potential of 39 pilocytic and 5 low grade astrocytomas was studied in relation to the Ki-67 activity as measured by the MIB-1 Labelings Index. The results were correlated to the biological behaviour of the tumor as measured by clinical and neuro-radiological (CT- or MRI-scans) follow-up of the patient. This study was undertaken to...
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Citations
... The researchers also discovered that SCID mice and TA-negative NSCLC cell lines [3 of 16 (19%)] showed significantly reduced invasive growth [66]. In vitro and animal evidence, which all demonstrated a noticeably worse prognosis in lung cancer patients expressing TA and/or hTERT, particularly in stage I NSCLC, supported the conclusions of multiple clinical trials [71][72][73][74]. Furthermore, TA and/or hTERT expression were linked to improved clinical staging, according to clinical investigations [75]. ...
Normal somatic cells inevitably experience replicative stress and senescence during proliferation. Somatic cell carcinogenesis can be prevented in part by limiting the reproduction of damaged or old cells and removing them from the cell cycle [1, 2]. However, Cancer cells must overcome the issues of replication pressure and senescence as well as preserve telomere length in order to achieve immortality, in contrast to normal somatic cells [1, 2]. Although telomerase accounts for the bulk of telomere lengthening methods in human cancer cells, there is a non-negligible portion of telomere lengthening pathways that depend on alternative lengthening of telomeres (ALT) [3]. For the selection of novel possible therapeutic targets for ALT-related disorders, a thorough understanding of the molecular biology of these diseases is crucial [4]. The roles of ALT, typical ALT tumor cell traits, the pathophysiology and molecular mechanisms of ALT tumor disorders, such as adrenocortical carcinoma (ACC), are all summarized in this work. Additionally, this research compiles as many of its hypothetically viable but unproven treatment targets as it can (ALT-associated PML bodies (APB), etc.). This review is intended to contribute as much as possible to the development of research, while also trying to provide a partial information for prospective investigations on ALT pathways and associated diseases.
... Using seven cancer types where each of the four stages had at least ten samples, we found in four of seven tested cancer types (THCA, KIRC, KIRP, and LUAD (lung adenocarcinoma)), EXTEND scores increased in high-stage tumors, suggesting higher telomerase activity in advanced-stage tumors consistent with previous reports [65][66][67][68] . In contrast, STAD and CRC showed the highest scores in stage I tumors (Fig. 3b). ...
Active telomerase is essential for stem cells and most cancers to maintain telomeres. The enzymatic activity of telomerase is related but not equivalent to the expression of TERT, the catalytic subunit of the complex. Here we show that telomerase enzymatic activity can be robustly estimated from the expression of a 13-gene signature. We demonstrate the validity of the expression-based approach, named EXTEND, using cell lines, cancer samples, and non-neoplastic samples. When applied to over 9,000 tumors and single cells, we find a strong correlation between telomerase activity and cancer stemness. This correlation is largely driven by a small population of proliferating cancer cells that exhibits both high telomerase activity and cancer stemness. This study establishes a computational framework for quantifying telomerase enzymatic activity and provides new insights into the relationships among telomerase, cancer proliferation, and stemness.
... High telomerase activity was detected almost 100% of SCLC cases and 80% of NSCLC samples using PCR technique. In addition, high telomerase activity in primary NSCLC cases was found to be correlated with elevated cell proliferation rates and advanced pathological stage [60]. It has also been found that more than 98% of SCLC cases showed upregulation of telomerase activity [57,61]. ...
... Several studies on the relationship between telomerase activity and prognosis in lung cancer have been reported (Hara et al., 2001;Marchetti et al., 1999). The expression of hTERT was frequently detected in lung cancer as was telomerase activity (Albanell et al, 1997;van den Berg et al., 2010;Wang et al., 2002) but the results of these studies are ambiguous. ...
Telomerase, undetectable in normal somatic cells, plays a critical role in carcinogenesis of the majority of human tumors including lung carcinoma. The aim of our study was to determine human telomerase reverse transcriptase (hTERT) mRNA expression in patients with non-small cell lung cancer (NSCLC) in order to estimate its usefulness as diagnostic and/or prognostic factor. hTERT expression was analyzed in a group of 12 females and 28 males with NSCLC using Quantitative Real-Time Polymerase Chain Reaction (QRT-PCR method) in cancerous and non-cancerous lung tissues. Results were analyzed according to clinical data and one-, two-, and five-year survival rates. hTERT expression in the cancerous tissue was significantly higher than in the lung parenchyma free from neoplasm infiltration (p < 0.05). There was no significant association between hTERT expression in the tumor tissue and age, gender, grading or clinical stage. A significant difference in hTERT expression between two types of histopathological patterns (adenocarcinoma and squamous cell carcinoma) was detected (p = 0.01). No association between hTERT expression in NSCLC specimens and survival rates was found. hTERT mRNA detection by QRT-PCR in tumor and corresponding cancer-free tissues can be used as a diagnostic marker in patients with NSCLC, but seems not to be a prognostic factor.
... Accumulating evidence has shown that the activity of telomerase is strongly correlated with the aggressiveness and metastatic potentials of various tumors. [26][27][28] The regulation of telomerase activity by hTERT results in inhibition of cancer cells apoptosis. Thus, hTERT is one of the most important targeted molecules of p53. ...
Background and objective:
Amarogentin has been reported to have a preventive effect on liver cancer via inducing cancer cell apoptosis. We attempted to elucidate the roles of p53-associated apoptosis pathways in the chemopreventive mechanism of amarogentin. The findings of this study will facilitate the development of a novel supplementary strategy for the treatment of liver cancer.
Materials and methods:
The purity of amarogentin was assessed by high-performance liquid chromatography. The inhibitory ratios of the liver cell lines were determined using a Cell Counting Kit-8 following treatment with a gradient concentration of amarogentin. Cell apoptosis was detected by flow cytometry using annexin V-fluorescein isothiocyanate/propidium iodide kits. The gene and protein expression of p53-associated molecules, such as Akt, human telomerase reverse transcriptase, RelA, and p38, was detected by real-time quantitative polymerase chain reaction, Western blotting, and immunohistochemical staining in liver cancer cells and mouse tumor tissues after treatment with amarogentin.
Results:
The inhibitory effect of amarogentin on cell proliferation was more obvious in liver cancer cells, and amarogentin was more likely to induce the apoptosis of liver cancer cells than that of normal liver cells. The gene and protein expression levels of Akt, RelA, and human telomerase reverse transcriptase were markedly higher in the control group than in the preventive group and treatment groups. Only the expression of human telomerase reverse transcriptase was downregulated, accompanied by the upregulation of p53.
Conclusion:
The results of our study suggest that amarogentin promotes apoptosis of liver cancer cells by the upregulation of p53 and downregulation of human telomerase reverse transcriptase and prevents the malignant transformation of these cells.
... Our measurements of telomerase activity in pulmonary parenchyma were confirmed by the results obtained by Metzger [5] and Albanell [6], who found higher telomerase activity in neoplastic lung specimens than in parenchyma samples from lungs that were deemed healthy. Other studies have shown high telomerase activity and hTERT expression in 75.8-93% of tumors [7,8]. ...
... On the other hand, Albanell did not confirm the existence of a positive association between telomerase activity and the level of differentiation (grade). However, he documented a strong correlation between telomerase activity and higher Ki-67 proliferation index [6]. Kumaki observed a positive association between telomerase activity and the level of differentiation (grade), but the results were not statistically significant [8]. ...
... Albanell analyzed 99 primary NSCLC tumor specimens. He found that the patients whose tumors were positive for telomerase activity did not live significantly longer than the patients in whom no telomerase activity was detected [6]. In their research, Chen and Wang also did not find telomerase activity in the tumor to have any prognostic impact [17,25]. ...
Introduction:
High telomerase activity has been detected in the majority of malignant neoplasms including lung cancer. The purpose of the study was to attempt to use telomerase activity as a prognostic factor in patients with non-small cell lung cancer (NSCLC).
Material and methods:
Telomerase activity was analyzed in 47 tissue specimens taken from patients with NSCLC. The control group consisted of 30 specimens of non-cancerous lung parenchyma. Telomerase activity was measured by means of the telomeric repeat amplification protocol (TRAP).
Results:
Telomerase activity in the neoplastic tissue was significantly higher than in the lung parenchyma that was free from neoplastic infiltration. There was no significant association between telomerase activity and age, gender, tobacco smoking, histological type of the tumor, or staging (pTNM). No association was found between the level of telomerase activity in NSCLC specimens and the two-year survival rate of patients (p = 0.326). A higher level of telomerase activity in poorly differentiated tumors (G3) as compared to moderately differentiated tumors (G2) was detected (p = 0.008). A positive association was identified between telomerase activity in pulmonary parenchyma free from tumor infiltration and the presence of leukocyte infiltration (p = 0.0001).
Conclusions:
No association was found between the level of telomerase activity in NSCLC specimens and the two-year survival rate of patients. The study has revealed a positive association between telomerase activity and the grade of differentiation (G) in NSCLC.
... It is not found in somatic cells but in germinative cells, stem cells and neoplastic cells making them immortal. The telomeric repeat amplifi cation protocol assay found telomerase activity in 86% of the NSCLC but not in normal tissue (1). ...
Lung cancer is the most common cause for cancer death in developed countries. The prognosis is dismal, with less than 15% of patients surviving 5 years after diagnosis, which is because of the lack of efficient diagnostic methods and successful treatment for metastatic disease. This led to a shift of the therapeutic paradigm towards asymptomatic preinvasive and early invasive cancer. Improvements in understanding the genetic and epigenetic alterations in the process of lung carcinogenesis are thus demanded in order to find new diagnostic approaches and targeted therapies. Due to the advances in molecular pathology the genetic charachteristics of the early preinvasive lesions in lung carcinogenesis are already known. This offers contemporary approaches for the early detection and diagnosis of this disease. The present review discusses recent advances in biomarker discovery and evaluation of their potential application in the clinical practice.
... Wesbuer [10] et al. investigate the human neuroblastomas, find out that increase the telomere length would lead to the decreasing of radio sensitivity, and the telomerase negative cells are significant more sensitive to irradiation. The same phenomena are observed in murine lymphoma cell and human primary lung cancer [11,12]. Taken together, these data suggest that telomere length and telomerase activity may be used as a potential diagnostic marker for detecting radio resistance. ...
Purpose: The telomere binding proteins play an important role in telomere function, which contribute greatly to the radio resistant in human cancers. This research is designed to investigate the relationship among the telomere length, telomerase activity and changes of telomere binding protein PTOP and TRF1 in radio resistant breast cancer cell lines.
Irradiate MDA-MB-435 s breast cancer cell with total dose of 60Gy delivered in 2Gy/fraction and 6Gy/fraction respectively, then measuring their telomere length by Southern blot analysis,telomerase activity by Telomerase PCR Elisa and detecting the expression of PTOP and TRF1 in both gene and protein levels. To further investigate the function of PTOP, using lentivirus technic to silence the PTOP gene and the detected the new silenced cells by southern blot and telomerase activity.
2 radio resistant breast cancer cell lines were successfully established. The MDA-MB-435 s R60/6 was (approximate 8.1-8.6kbp) about 2-2.4 folds to the patent cell (3.6-4.2kbp), the MDA-MB-435 s R60/2 cell (approximate 5.3-6.3kbp) was about 1.3-1.75 fold to the parent cell line. The telomerase activity was more enhanced in radio resistant cell lines than the parent cell. The expression of PTOP and TRF1 were significant increased in radio resistant cell lines than the patent cell in both gene and protein level. Otherwise, after using lentivirus technic to silence the PTOP gene, we found the radio resistant cell lines were significant decrease their radio resistances and telomerase activities.
The telomere binding protein PTOP and TRF1 were increased expressed in radio resistant breast cancer cell, PTOP was observed instinct positive correlated with telomere lengthen and telomerase activity enhancement.
... Wysoką aktywność tego enzymu stwierdzono w prawie 100% przypadków DRP i w około 80% przypadków NDRP [69]. Oznaczanie aktywności telomerazy może być przydatnym markerem prognostycznym w raku płuca, jednak wskaźnik ten nie koreluje ze stopniem zaawansowania klinicznego i typem patomorfologicznym nowotworu [65]. ...
STRESZCZENIE Rak płuca jest najczęściej występującym nowotworem złośliwym i stanowi główną przyczynę zgonów na świecie. Pomimo stałego postępu w diagnostyce i terapii 5-letnie przeżycia pozostają niezadowalające, co spowodowane jest głównie rozpoznawaniem tego nowotworu w wysokim stopniu zaawansowania i brakiem możliwości radykal-nego leczenia chirurgicznego. Stały postęp w metodach diagnostycznych i terapeutycznych, związany w dużej mierze z wykorzystaniem technik biologii molekularnej, rodzi nadzieje na poprawę rokowania u chorych na raka płuca. W pracy przedstawiono podłoże molekularne raka płuca, opisano najważniejsze funkcje białek p53, Rb, p16, MYC, RAS oraz skutki mutacji w kodujących je genach. Autorzy przedstawili również wpływ czynników wzro-stowych, apoptozy, angiogenezy oraz telomerazy na rozwój procesu nowotworowego, a także nieprawidłowości genetyczne, które mogą służyć za molekularne czynniki predykcyjne. Słowa kluczowe: rak płuca, podłoże molekularne raka płuca, molekularne czynniki predykcyjne ABSTRACT Lung cancer is the most common malignant neoplasm and the main cause of human death. Despite persistant development in the dignostics and therapy process, 5-year survival is still unsatisfactory. It is caused mostly by detecting lung cancer in advanced stage and that is why there is no posibility for radical treatment resection. Diagnostic and therapeutical progress in molecular biology creates a chance to make overall survival longer. In this paper authors present molecular determinants of lung cancer including main functions of p53, Rb, p16. MYC, RAS proteins and consequences of mutations within the genes encoding them. There is also showed a role of growth factors, apoptosis, angiogenesis and telomerase in the oncogenic transformation. Beside this authors descibed genetics dycfunctions which may be a molecular predictive factos for lung cancer. Wstęp Rak płuca jest jednym z najczęściej występujących nowotworów złośliwych w większości krajów i stanowi główną przyczynę zgonów na świecie wśród chorób nowotworowych. Szacuje się, że każdego roku rak płuca jest rozpoznawany u niemal 1 miliona mężczyzn i 400 ty-sięcy kobiet [1]. Nowa klasyfikacja TNM z 2009 roku obejmuje podział tego nowotworu na drobnokomórko-wego raka płuca (DRP) oraz niedrobnokomórkowego raka płuca (NDRP), do którego należy rak płaskona-błonkowy, gruczolakorak, rak wielkokomórkowy oraz inne — bardzo rzadkie typy patomorfologiczne. Rako-wiak, który jak dotąd nie podlegał żadnej klasyfikacji i nie przypisywano mu żadnego stopnia zaawansowania klinicznego, teraz został uwzględniony w obrębie sys-temu TNM [2]. Mimo stałego postępu w diagnostyce i terapii wskaźniki przeżycia chorych z rozpoznaniem niedrob-nokomórkowego raka płuca wciąż pozostają niezado-walające. Przeżycia 5-letnie wynoszą około 15% [3, 4], co jest spowodowane głównie rozpoznawaniem tego
... This is supported by the observation that early stage neuroblastomas have low telomerase activity (39). Other studies have suggested that telomerase activity is correlated with pathological stage (40,41) or tumor aggressiveness (42). Thus, the lack of telomerase limits the growth of rapidly proliferating cells while the increase in telomerase permits indefinite proliferations. ...
Guanine rich sequence have the ability to fold into stable 4 stranded structures called G-quadruplex under physiological concentrations of Na+ or K+. G-quadruplexes are found in telomeres, being stable structures under the control of telomerase binding proteins. They are also identified throughout the genome and are enriched in promoter regions of protein coding genes, upstream and downstream of the transcription initiation sites. A number of these promoter quadruplexes have been investigated for several proto-oncogenes. The formation of these quadruplexes can lead to chemical intervention of gene expression using a G-quadruplex binding ligand. We review location, configuration, and stabilization of these quadruplexes in some of the important promoters with regards to their potential as anticancer target.
