Mieczyslaw Piatyszek

Independent Researcher

Synthesis of DNA at chromosome ends by telomerase may be necessary for indefinite proliferation of human cells. A highly sensitive assay for measuring telomerase activity was developed. In cultured cells representing 18 different human tissues, 98 of 100 immortal and none of 22 mortal populations were positive for telomerase. Similarly, 90 of 101 b...

The association of human telomerase activity with an indefinite replicative capacity of cells in vitro and advanced tumors in vivo is gaining wide support. The increasing interest in studying various aspects of telomerase expression in cancer required the development of a sensitive and reliable protocol for the extraction and detection of telomeras...

Telomerase activity was analysed in 100 neuroblastoma cases. Although telomerase activity was not detected in normal adrenal tissues or benign ganglioneuromas, almost all neuroblastomas (94%) did express it, suggesting an important role for telomerase in neuroblastoma development. Neuroblastomas with high telomerase activity had other genetic chang...

Telomerase is a ribonucleoprotein that synthesizes telomere repeats onto chromosome ends and is involved in maintaining telomere length in germline tissues and in immortal and cancer cells. In the present study, the temporal regulation of expression of telomerase activity was examined in human germline and somatic tissues and cells during developme...

This is the first report describing up-regulation of telomerase activity in human normal cells. Telomerase, a ribonucleoprotein enzyme, has been thought to be involved in maintaining telomere length stability in germline and most cancer cells, but not in normal cells. However, in the present study, we demonstrate that telomerase activity is detecta...

Protein-based therapeutics have revolutionized the pharmaceutical industry and become vital components in the development of future therapeutics. They offer several advantages over traditional small molecule drugs, including high affinity, potency and specificity, while demonstrating low toxicity and minimal adverse effects. However, the developmen...

A series of oligonucleotide conjugates were designed and synthesized as novel inhibitors of human telomerase. These compounds contain a relatively short (6-7-mer) oligonucleotide domain, with an N3'-->P5' phosphoramidate (np) or thio-phosphoramidate (nps) backbone, targeted to the template region of the RNA component of the enzyme and various penda...

Human telomerase is a reverse transcriptase that is expressed in essentially all cancer cells, but not in the vast majority of normal somatic cells. Therefore, the specific inhibition of telomerase activity in tumors might have significant beneficial therapeutic effects. We have designed and evaluated oligonucleotide N3' --> P5' thio-phosphoramidat...

Telomerase, the enzyme responsible for proliferative immortality, is expressed in essentially all cancer cells, but not in most normal human cells. Thus, specific telomerase inhibition is potentially a universal anticancer therapy with few side effects. We designed N3'-->P5' thio-phosphoramidate (NPS) oligonucleotides as telomerase template antagon...

A Lupinus luteus chloroplast clone bank was analysed for the presence of ndh genes using tobacco heterologous probes. Six ndh genes, ndhC, ndhK, ndhJ, ndhD, ndhE and ndhF, were identified. A BamHI clone 14, consisting of a 9 kb insert, was partially sequenced. A 1.9 kb long sequence was found to contain ndhC, ndhK and ndhJ genes (EMBL accession no....

To investigate the role of telomerase in the multistage pathogenesis of lung cancer, we examined 205 fresh and archival tissue samples obtained from 40 patients, 34 of whom had invasive lung carcinoma, 5 with carcinoma in situ (CIS) without invasion, and 1 without lung carcinoma. We analyzed samples for telomerase enzyme activity using the semiquan...

Telomerase, the enzyme that stabilizes telomere length, is reactivated with almost all cancer types, and it may be necessary for unlimited cell proliferation. Assessment of malignancy in ordinary meningiomas is inconclusive because no clear-cut correlation exists between aggressive clinical behavior and histological features or karyotypic abnormali...

Telomerase, an enzyme associated with cellular immortality, is expressed by most malignant tumours, but is inactive in normal somatic cells except for male germ cells and proliferating stem cells. Thus, the measurement of telomerase activity in tissue samples may provide useful diagnostic and prognostic information. The aim of this study was to det...

Chromosome end-to-end associations seen at metaphase involve telomeres and are commonly observed in cells derived from individuals with ataxia telangiectasia and most types of human tumors. The associations may arise because of short telomeres and/or alterations of chromatin structure. There is a growing consensus that telomere length is stabilized...

Telomeres of most eucaryotes terminate in long stretches of short, guanine-rich repeats. Telomerase, a specialized enzyme with reverse transcriptase-like activity, has been shown to synthesize these repeats in many lower eucaryotes and several animal species. Although a sequence (TTTAGGG)n that matches the eucaryotic consensus sequence Tx(A)Gy is p...

Telomeres have a vital role in maintaining chromosome stability and are essential for long term viability. Since the very ends of linear chromosomes cannot replicate, telomeres shorten in normal somatic cells eventually resulting in growth inhibition. However, most immortal cell lines maintain stable telomeres indicating that mechanisms exist to co...

The terminal regions of human chromosomes, the telomeres, shorten with each cell division in most normal somatic cells. Telomerase, a ribonucleoprotein that synthesizes telomeric DNA onto chromosomal ends, is activated in germline cells and almost all tumor cells. Telomerase activity maintains the stability of telomere length, resulting in indefini...

We report the inhibition of human telomerase activity by peptide nucleic acids (PNAs). PNAs recognize the RNA component of human telomerase (hTR) and inhibit activity of the enzyme with IC50 values in the picomolar to nanomolar range. Inhibition depends on targeting exact functional boundaries of the hTR template and is 10- to 50-fold more efficien...

Hybrids between immortal cells that express telomerase and normal cells that lack telomerase have a limited lifespan. We demonstrate that telomerase is repressed in such hybrids. Treatment of immortal human cell lines with certain oligonucleotides resulted in telomere elongation. We took advantage of this observation to test the hypothesis that elo...

Telomeres are the end regions of linear chromosomes, and in normal somatic cells the lengths of telomeres shorten with successive cell divisions. Telomerase, a ribonucleoprotein enzyme, maintains the length of telomeres in immortal and germline cells. Although present in human fetal tissues, shortly after birth telomerase activity is not detectable...

Telomerase activity has been detected in many human immortal cells lines and in tumor tissues, whereas it is generally absent from primary cell strains and from many tumor adjacent tissue samples. With the recently cloned human telomerase RNA (hTR), we used Northern analysis to follow the levels of hTR in primary, precrisis, and immortalized cells....

We urgently need biochemical markers to detect the malignant nature and pathological states of the human prostate. We report that telomerase activity is associated with prostate cancer but absent in the benign disease and normal gland. Telomerase is, therefore, a potential diagnostic marker for prostate cancer. Twenty-five human prostates resected...

The activity of the ribonucleoprotein enzyme telomerase is not detected in normal somatic cells; thus, with each cell division, the ends of chromosomes consisting of the telomeric repeats TTAGGG progressively erode. The current model gaining support is that telomerase activity in germline and immortal cells maintains telomere length and thus compen...

Malignant gliomas are invasive into surrounding brain and are refractory to therapy. Telomerase stabilises telomere length and may immortalise cells to allow unlimited proliferation. Our analysis of telomerase activity in 90 human gliomas showed that 19 of 19 oligodendrogliomas and 38 of 51 glioblastoma multiformes have detectable telomerase activi...

In humans, the amount of terminal (TTAGGG)n, telomeric DNA decreases during aging of various somatic cell types in vitro and in vivo. While the factors accounting for telomere shortening have not been thoroughly established, the inability of the DNA replication machinery to completely copy chromosomal termini (the "end replication problem") and the...

Although many genetic alterations have been reported in gastric cancer, it is not known whether all gastric tumors are capable of indefinite proliferative potential, e.g., immortality. The expression of telomerase and stabilization of telomeres are concomitant with the attainment of immortality in tumor cells; thus, the measurement of telomerase ac...

Background: Telomerase is an enzyme that adds hexameric TTAGGG nucleotide repeats onto the ends of vertebrate chromosomal DNAs (i.e., telomeres) to compensate for losses that occur with each round of DNA replication. Somatic cells do not have telomerase activity and stop dividing when the telomeric ends of at least some chromosomes have been short...

Individuals with germ line mutations in the p53 gene, such as Li-Fraumeni syndrome (LFS), have an increased occurrence of many types of cancer, including an unusually high incidence of breast cancer. This report documents that normal breast epithelial cells obtained from a patient with LFS (with a mutation at codon 133 of the p53 gene) spontaneousl...

Mitochondrial DNA (mtDNA) fragments can be found inserted into nuclear DNA and may contribute to cancer and aging. A HeLaTG-cell nuclear transcript was shown to include human cytochrome oxidase subunit 3 (coxIII) mtDNA fused to c-myc sequences. Independently, a coxIII-containing cDNA was discovered to replicate autonomously in HeLa cells. We show t...

Iodo-Gen (1,3,4,6-tetrachloro-3a,6a-diphenylglycoluril), widely used as an oxidizing agent for iodination of proteins, can also be used for iodination of nucleic acids. Optimal conditions were determined for efficient labeling of RNA and DNA with 125I. The proposed procedure for radioiodination of nucleic acids is more beneficial than the methods u...

RNA binding properties of proteins from the large subunit of bovine mitochondrial ribosomes were studied using four different approaches: binding of radiolabeled RNA to western blotted proteins; disassembly of the intact 39 S ribosomal subunits with urea; binding of ribosomal proteins to RNA in the presence of urea; and binding of proteins extracte...