Low-dose chemotherapy delays relapse of a dominated and resistant sub-population in a heterogeneous human SCLC xenograft in nude mice
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Low-dose chemotherapy delays relapse of a dominated and resistant sub-population in a heterogeneous human SCLC xenograft in nude mice. / Aabo, K; Vindeløv, L L; Christensen, I J; Spang-Thomsen, M.
I: International Journal of Cancer, Bind 59, Nr. 3, 1994, s. 394-9.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Low-dose chemotherapy delays relapse of a dominated and resistant sub-population in a heterogeneous human SCLC xenograft in nude mice
AU - Aabo, K
AU - Vindeløv, L L
AU - Christensen, I J
AU - Spang-Thomsen, M
N1 - Keywords: Animals; Carcinoma, Small Cell; Carmustine; DNA, Neoplasm; Drug Resistance; Humans; Lung Neoplasms; Male; Mice; Mice, Nude; Mitosis; Neoplasm Recurrence, Local; Neoplasm Transplantation; Transplantation, Heterologous; Tumor Cells, Cultured
PY - 1994
Y1 - 1994
N2 - We investigated the influence of cellular heterogeneity on the response to low-dose BCNU chemotherapy of an artificially mixed human small-cell lung cancer (SCLC) xenograft in nude mice containing a BCNU-sensitive and dominating sub-population and a BCNU-resistant and undetectable (dominated) sub-population. The cell lines differed in DNA content, making them distinguishable by DNA flow cytometry (FCM). After 3 weeks of tumor growth, the mice were stratified according to tumor size and randomized to 2 different low-dose treatments with BCNU or no treatment. After a further 3 to 4 weeks, a high-dose treatment (LD10) was given to both groups of treated tumors. Changes in the relative proportions of and cell lines in the tumors were measured by FCM on fine-needle tumor aspirates. At the time of low-dose treatment, all the tumors were totally dominated by the sensitive cells. A temporary response was seen after low-dose treatment. After the high-dose treatment, a similar short response was seen. In the non-treated group, the sensitive cells continued to dominate. At the time of tumor regrowth after the low-dose treatment, most of the tumors continued to be dominated by the sensitive population. At the time of progression after the response to the high-dose treatment, the resistant cell line was the predominant population. If compared with a single high-dose BCNU treatment, the response of tumors treated with a low dose was superior, indicating that the presence of a dominating and slower growing sub-population influenced the outcome of the treatment.
AB - We investigated the influence of cellular heterogeneity on the response to low-dose BCNU chemotherapy of an artificially mixed human small-cell lung cancer (SCLC) xenograft in nude mice containing a BCNU-sensitive and dominating sub-population and a BCNU-resistant and undetectable (dominated) sub-population. The cell lines differed in DNA content, making them distinguishable by DNA flow cytometry (FCM). After 3 weeks of tumor growth, the mice were stratified according to tumor size and randomized to 2 different low-dose treatments with BCNU or no treatment. After a further 3 to 4 weeks, a high-dose treatment (LD10) was given to both groups of treated tumors. Changes in the relative proportions of and cell lines in the tumors were measured by FCM on fine-needle tumor aspirates. At the time of low-dose treatment, all the tumors were totally dominated by the sensitive cells. A temporary response was seen after low-dose treatment. After the high-dose treatment, a similar short response was seen. In the non-treated group, the sensitive cells continued to dominate. At the time of tumor regrowth after the low-dose treatment, most of the tumors continued to be dominated by the sensitive population. At the time of progression after the response to the high-dose treatment, the resistant cell line was the predominant population. If compared with a single high-dose BCNU treatment, the response of tumors treated with a low dose was superior, indicating that the presence of a dominating and slower growing sub-population influenced the outcome of the treatment.
M3 - Journal article
C2 - 7927948
VL - 59
SP - 394
EP - 399
JO - International Journal of Cancer
JF - International Journal of Cancer
SN - 0020-7136
IS - 3
ER -
ID: 12870280