Contribution ofin vivo proliferation/differentiation studies toward the development of a combined functional and morphologic system of classification of neoplastic diseases

Abstract

Proliferation kinetics of both leukemia and a variety of solid tumors have been assessed after in vivo infusions of the thymidine analogues, iododeoxyuridine (IUdR) and bromodeoxyuridine (BrdU). In acute myeloid leukemia (AML), these data indicate that the pretherapy cell cycle time (Tc) of myeloblasts is a prognostic indicator for remission duration since patients with slowly cycling myeloblasts had more durable remissions. The presence of in vivo differentiation detected from the day 7 biopsy after chemotherapy was also of favorable prognosis as these individuals had statistically significant improvement in their remission duration. The data in solid tumors are not mature enough for determining their clinical significance. Since cell kinetic information is readily available in a prompt fashion using these novel techniques, data can be used to plan therapeutic strategies for patients. This review discusses the state‐of‐the‐art techniques available for cell cycle kinetic studies and the clinical and prognostic utility of data that have been generated thus far. Cancer 1992; 69:1557‐1566.

Kinetic Analysis of Tumor Cells in Bone and Soft Tissue Sarcomas.

“…Accordingly, the present results were compared with the published results in different fields (Table 4). It has been reported that BrdU-LI was 25.4% in almost 300 cases of acute myeloid leukemia [20], 25.8% in 8 cases of colorectal cancer [34] and 12.9% in 4 cases of breast cancer [20]. These values are essentially the same as 19.2% (5-37%) observed in the present study.…”

“…These values are essentially the same as 19.2% (5-37%) observed in the present study. Ts was 15.4 hr in acute myeloid leukemia [20], 18.7 hr in colorectal cancer [34] and 23.3 hr in breast cancer [20], whereas that in the present study was 22.9 hr (13-34 hr). Tc was 66.9 hr in acute myeloid leukemia [20], 76.8 hr in colorectal cancer [34] and 235 hr in breast cancer [20], whereas that in the present study was 159 hr (77-536 hr).…”

“…They also described that Tp and BrdU-LI was closely related, and Tp can be estimated from BrdU-LI. In acute myeloid leukemia [20], breast cancer colorectal cancer [20,34] and non-Hodgkin's lymphoma [20,32], cell kinetics was also analyzed in situ by direct injection of BrdU and IUdR into patients, and Ts and Tc have been obtained. Tc is Tp before multiplied by Steel's coefficient.…”

“…Using the double staining technique with these compounds, several studies of calculation of the Sphase duration and theoretical doubling time of tumor cells have been reported [20,25,32,34] in fields other than musculoskeletal tumors.…”

Kinetic Analysis of Malignant Fibrous Histiocytoma Cells Treated with Anticancer Agents In Vivo.

“…Since this double-labeling procedure has a time lag of 2 hr, the proportion (dS) of cells not in the DNA synthesis phase during the double-labeling experiments could be derived from a stain sample. The values of Ts and Tc were therefore calculated on the basis of the dS [15,19,20,22]. In brief, they were calculated as follows: dS = blue/(brown + double) Ts =time lag/dS Tc=Ts/LI x growth fraction The growth fraction was considered to be an approximate value of the PCNA labeling index (PCNA-LI), and it was obtained as follows.…”