Detecting human bladder carcinoma cells in voided urine samples by assaying for the presence of telomerase activity

Kavaler, Elizabeth; Landman, Jaime; Chang, Yongli; Droller, Michael J.; Liu, Brian C.‐S.

doi:10.1002/(sici)1097-0142(19980215)82:4<708::aid-cncr14>3.0.co;2-1

Cited by 137 publications

(57 citation statements)

References 20 publications

(7 reference statements)

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“…Corroborating preliminary results of our group 15 and others, [16][17][18][19] we have identified telomerase-based tests as valuable alternatives to cytology. Compared to other urine-based markers, quantitative detection of hTR expression by RT-PCR shows acceptable diagnostic accuracy with more than 70% of samples correctly classified.…”

Section: Discussionsupporting

confidence: 70%

“…14 Detection of telomerase has emerged as a promising approach for diagnosing bladder cancer, and encouraging results have been reported in preliminary studies by our group 15 and others. [16][17][18][19] The human telomerase enzyme is composed of 2 essential subunits: hTR 20 and hTERT. 21 In human somatic cells, this enzyme is usually repressed but becomes reactivated with the attainment of immortality in most types of cancer.…”

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confidence: 99%

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Quantitative evaluation of telomerase subunits in urine as biomarkers for noninvasive detection of bladder cancer

Weikert

Krause

Wolff

et al. 2005

Intl Journal of Cancer

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The aim of our study was to prospectively evaluate the potential diagnostic value and clinical applicability of quantitative analysis of telomerase subunits gene expression in urine for noninvasive detection of bladder cancer. Expression levels of human telomerase reverse transcriptase (hTERT) and human telomerase RNA (hTR) were analyzed by real-time reverse transcriptase polymerase chain reaction (RT-PCR) in urine samples from 163 subjects with bladder cancer and 237 controls (163 individuals with benign genitourinary diseases; 74 healthy subjects). The sensitivity, specificity and optimal cutoffs were determined and compared to the corresponding values obtained by voided urine cytology. Quantitative urinary hTR analysis detects bladder cancer with an overall sensitivity of 77.0%, whereas hTERT analysis reached a sensitivity of 55.2%. The majority of undetected tumors were small, lowgrade pTa lesions. Both hTR and hTERT proved to be significantly more sensitive than cytology (34.5%; p < 0.001). Specificities for hTR, hTERT and cytology were 72.1%, 85.0% and 92.7%, respectively, in the total study population and 96.9%, 89.2% and 100%, respectively, in healthy subjects. Higher diagnostic accuracy was achieved by hTR than by hTERT analysis (p < 0.05). The specificity of hTR increased to 85.0% in the total population if urinary leukocyte contamination was excluded. These data suggest that quantitative hTR analysis is the most accurate telomerase-based test for bladder cancer detection and has the potential to replace cytology as a noninvasive biomarker for disease diagnosis and follow-up. ' 2005 Wiley-Liss, Inc.

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Section: Discussionsupporting

confidence: 70%

mentioning

confidence: 99%

Quantitative evaluation of telomerase subunits in urine as biomarkers for noninvasive detection of bladder cancer

Weikert

Krause

Wolff

et al. 2005

Intl Journal of Cancer

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“…For detection of bladder carcinoma in urine speciments, telomerase is proved far more sensitive than cytology or other available screenings. In two independent studies, the sensitivity of telomerase was 85% and 70%, compared with 51% and 44% for cytology [33], [34].…”

Section: Telomerase Assay and The Diagnosis Of Cancermentioning

confidence: 99%

Telomere and telomerase in oncology

Wei

2002

Cell Res

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Shortening of the telomeric DNA at the chromosome ends is presumed to limit the lifespan of human cells and elicit a signal for the onset of cellular senescence. To continually proliferate across the senescent checkpoint, cells must restore and preserve telomere length. This can be achieved by telomerase, which has the reverse transcriptase activity. Telomerase activity is negative in human normal somatic cells but can be detected in most tumor cells. The enzyme is proposed to be an essential factor in cell immortalization and cancer progression. In this review we discuss the structure and function of telomere and telomerase and their roles in cell immortalization and oncogenesis. Simultaneously the experimental studies of telomerase assays for cancer detection and diagnosis are reviewed. Finally, we discuss the potential use of inhibitors of telomerase in anti-cancer therapy.Key words: Telomere, telomerase, cancer, telomerase assay, inhibitor. REVIEWTelomere and cell replicative senescence Telomeres, which are located at the end of chromosome, are crucial to protect chromosome against degeneration, rearrangment and end to end fusion [1]. Human telomeres are tandemly repeated units of the hexanucleotide TTAGGG. The estimated length of telomeric DNA varies from 2 to 20 kilo base pairs, depending on factors such as tissue type and human age. The buck of telomeric DNA is doublestranded, but the end of telomeric DNA consists of 3' overhang of single-stranded repeats. Sequencespecific DNA-binding proteins (TRF1 and TRF2) attach to the telomeric DNA repeats. These proteins help maintain telomere stability and regulate telomere length [2].Owing to the nature of lagging-strand DNA synthesis, traditional DNA polymerases are unable to completely replicate the ends of linear DNA [3]. Incomplete replication leads to the loss of 50-200 base pairs of the end of telomeric DNA with each round of DNA replication. Hence, the continual cycles of cell growth and division bring on progressing telomere shortening [4]. Now it is clear that telomere shortening is responsible for inducing the senescent phenotype that results from repeated cell division, but the mechanism how a short telomere induces the senescence is still unknown. Possible mechanism includes the short telomere inducing a DNA damage response, releasing transcriptional regulatory factors from sequestration, and relaxing heterochromatin which can lead to the arrest of cell growth and the cell senescence [5]. Senescence represents a state in which cells no longer proliferate but remain viable for extended periods. The cells which are about to enter the senescent state can be induced to bypass senescence through the introduction of viral oncogenes such as SVA40 Large T antigen (LT) and the HPV E6 or E7 protein. These viral proteins can inactivate p53 and Rb tumor suppressor pathways, which play a pivotal role in inducing the senescence phenotype. These cells that bypass senescence state continue to proliferate and suffer from further telomere loss. So the shortening

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“…Telomeraz aktivitesi ELİSA bazlı TRAP kitleri kullanılarak veya PCR yöntemi de eklenerek hem tümör dokusunda hem de dökülen tümör hücrele-rinden idrarda bakılan telomeric repeat Amplification Protocol (TRAP) ile (34,35) veya gene idrar ör-neklerinde RT-PCR yöntemi ile telomeraz RNA kompotentinin belirlenmesi ile ölçülebilir. İkinci testin avantajı daha hızlı sonuç vermesi ve daha kolay yapılmasıdır (36,37).…”

Section: ö öZ Ze Et Tunclassified

“…Kapsamlı bir şekilde değerlendirildiğinde mesane kanserlerinde telomerazın sensitivitesi %70-86 arasında değişmektedir (35,38). Eğer mesane yıkama sıvısı ile idrar örneği birlikte kullanılırsa sensitivite %95'e yükselmektedir.…”

Section: ö öZ Ze Et Tunclassified

Mesane Tümörleri̇nde Tümör Beli̇rleyi̇ci̇leri̇

Şahinli¹,

Göğüş²,

Göğüş³

2003

Ankara Üniversitesi Tıp Fakültesi Mecmuası

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Ö ÖZ ZE ET TMesane kanserleri yüksek insidansa sahip, tekrar etme eğilimi yüksek, sıkı ve düzenli takibi gereken tümörlerdir. Mesane kanserinin değerlendirilmesinde günümüzde ultrasonografi, intravenöz pyelografi ve sistoskopi sıklıkla kullanılmaktadır. Bu metodlar yüksek belirleme oranına sahip olmakla birlikte pahalı, zaman alıcı ve invaziv yön-temlerdir. Bu nedenle, yüksek sensitivite ve spesifite oranlarına sahip, noninvaziv, çabuk sonuç veren testlere gereksinim vardır. Son yıllarda mesane tümörlerinin tanı ve takibinde kullanılan çok sayıda tümör belirleyicisi mevcuttur. Bu derlemede bu tanısal testler özellikleri, uygulanışları ve doğruluk oranları açısından detaylı olarak tartışılmıştır.A An na ah ht ta ar r K Ke el li im me el le er r: : Mesane Kanseri, Tanı, İzlem, Tümör Belirleyicileri S SU UM MM MA AR RY Y T Tu um mo or r M Ma ar rk ke er rs s F Fo or r B Bl la ad dd de er r C Ca an nc ce er rs s Bladder cancers have a high incidence and high tendency to recur, necessitating close and regular follow-up. Current methods for evaluation of bladder cancers include ultrasonography, intravenous pyelography and cystoscopy. Although, these methods have a high detection rate, they are expensive, time-consuming and invasive. Therefore, there is need for noninvasive, quick diagnostic tests with a high sensitivity and specifity for the detection of bladder cancer. In last years there are an increasing number of tumor markers avaliable for the detection of bladder cancer. The specialities, applications and the detection rates of these diagnostic markers were discussed in detail in this review.K Ke ey y W Wo or rd ds s: : Bladder Cancer, Diagnosis, Follow-up, Tumor Markers Mesane kanserleri organizmanın en sık görü-len tümörlerindendir. Genel istatistiklere göre erkeklerde 4. sıklıkta görülür ve tüm kanserlerin %10'unu oluşturur. Kadınlarda ise 8. sıradadır ve kadın kanserlerinin %4'ü mesane kanserleridir. Ülkemizde sağlıklı istatistikler olmamakla birlikte dünya ortalamasının üstünde bir mesane tümörü insidansı olduğu düşünülmektedir. Genel olarak bakıldığına dünyada yılda 200.000 yeni mesane tümörlü vaka saptanmakta (1), ayrıca sadece Avrupa'da bu sayı 66.000 olarak belirlenmektedir (2). A.B.D.'de 1999 yılında yaklaşık olarak 54.000 mesane tümörü vakası tespit edilmiş olup, bunların yaklaşık olarak 12.000'i ölümle sonuçlanmıştır (3).Mesane tümörlerinin %70'i ilk saptandığında yüzeyel mesane tümörüdür ve bunlar 5 yıl içeri-sinde yaklaşık %70 oranında nüks eder ve 15 yıl içerisinde bu oran %90'lara kadar yükselmektedir (4). Mesane tümörlerinin %30'u ise ilk tanı konulduğunda invaziv tümördür ve bunların yarından fazlası ise uzak metastaz yapmış durumdadır (4).

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Detecting human bladder carcinoma cells in voided urine samples by assaying for the presence of telomerase activity

Cited by 137 publications

References 20 publications

Quantitative evaluation of telomerase subunits in urine as biomarkers for noninvasive detection of bladder cancer

Quantitative evaluation of telomerase subunits in urine as biomarkers for noninvasive detection of bladder cancer

Telomere and telomerase in oncology

Mesane Tümörleri̇nde Tümör Beli̇rleyi̇ci̇leri̇

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