Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Dysregulation of telomerase activity and expression in lymphokine-activated killer cells from advanced cancer patients: Possible involvement in cancer-associated immunosuppression mechanism
Autore:
Minami, K; Yamaguchi, Y; Yoshida, K; Quan, CP; Toge, T;
Indirizzi:
Hiroshima Univ, Res Inst Radiat Biol & Med, Dept Surg Oncol, Minami Ku, Hiroshima 7348553, Japan Hiroshima Univ Hiroshima Japan 7348553 nami Ku, Hiroshima 7348553, Japan
Titolo Testata:
ONCOLOGY REPORTS
fascicolo: 3, volume: 8, anno: 2001,
pagine: 649 - 653
SICI:
1021-335X(200105/06)8:3<649:DOTAAE>2.0.ZU;2-1
Fonte:
ISI
Lingua:
ENG
Soggetto:
PERIPHERAL-BLOOD LYMPHOCYTES; TGF-BETA; DIFFERENTIATION; IMMUNOTHERAPY; MODULATION; CARCINOMA; INFECTION; LENGTH;
Keywords:
telomere; telomerase; lymphokine-activated killer cells; immunosuppression;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Citazioni:
23
Recensione:
Indirizzi per estratti:
Indirizzo: Yamaguchi, Y Hiroshima Univ, Res Inst Radiat Biol & Med, Dept Surg Oncol, Minami Ku, Kasumi 1-2-3, Hiroshima 7348553, Japan Hiroshima Univ Kasumi 1-2-3 Hiroshima Japan 7348553 3, Japan
Citazione:
K. Minami et al., "Dysregulation of telomerase activity and expression in lymphokine-activated killer cells from advanced cancer patients: Possible involvement in cancer-associated immunosuppression mechanism", ONCOL REP, 8(3), 2001, pp. 649-653

Abstract

There exists cancer-associated immunosuppression, and the generation of lymphokine-activated killer (LAK) cells is impaired in patients with advancedcancer. Telomerase has been reported to be upregulated in the activation of lymphocytes to proliferate against immune stimulation as well as in the malignant transformation of immortal cancer cells. We attempted to clarify the involvement of telomerase in the impairment of LAK cell generation in patients with advanced cancer. LAK cells were generated by stimulation with interleukin (IL)-2 and immobilized anti-CD3 antibody (IL-2/ CD3 system) fromperipheral blood mononuclear cells of healthy volunteers (he-LAK) or patients with advanced cancer (ca-LAK), and proliferative potential of LAK cellswas evaluated on the basis of population doubling level (PDL). Telomere length and telomerase activity of LAK cells were measured by the hybridization with oligonucleotide (TTAGGG)4 and by the telomeric repeat amplification protocol (TRAP) assay, respectively. Effects on telomerase activity in LAK cells of serum from cancer patients, transforming growth factor (TGF)-beta,and IL-10 were also examined. The lifespan of ca-LAK (15.2+/-5.1 PDLs) wassignificantly shorter than that of he-LAK (22.6+/-8.3 PDLs) (p=0.0358). There were no significant differences between he- and ca-LAK in telomere length before IL-2/CD3 stimulation and maximal telomerase activity induced. Thetelomerase activity induced in ca-LAK failed to elongate sufficiently the telomeric ends (-35.2+/-46.2 bp) compared with that in he-LAK (16.8+/-41.5 bp) (p=0.0448). The telomerase activity was initially detectable on day 2 in all he-LAK, whereas 8 (61.5%) of 13 ca-LAK expressed telomerase activity on day 3 or later following the stimulation, showing a significant retardation of telomerase expression (p=0.0116). The addition to the LAK cell generation system of serum From cancer patients, as well as IL-10, but not transforming growth factor (TGF)-beta, suppressed the telomerase activity. This serum-induced suppression of telomerase activity in LAK cells was abrogatedwith the addition of anti-IL-10 antibody but not with anti-TGF-beta antibody. It is suggested that the dysregulation of telomerase activity and expression exists in LAK cells of cancer patients, resulting in the impairment of LAK cell generation in patients with advanced cancer. Serum IL-10 may be involved in the impairment of LAK cell generation by the suppression of telomerase activity of lymphocytes in vivo. Thus, the dysregulation mechanism of telomerase activity and expression in lymphocytes of cancer patients maybe attributable, in part, to cancer-associated immunosuppression.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 09/04/20 alle ore 06:31:39