Growth Fraction of Colorectal Carcinoma (Ki67): A Comparative Study

1992 ◽  
Vol 7 (2) ◽  
pp. 93-96 ◽  
Author(s):  
A. Benetti ◽  
A. Berenzi ◽  
P. Grigolato

We studied the growth fraction of55 resected colorectal adenocarcinomas by means of a three-step immunoperoxidase technique (avidin-biotin-peroxidase) using the monoclonal antibody Ki67 directed against a cell proliferation-associated nuclear antigen. The percentage of Ki67-positive cells was evaluated independently by two observers, and a Ki67 score was obtained for each case. No correlation was observed between Ki67 staining and patient's age and sex, tumor size and localization or grading and staging according to Dukes’ method (modified by Astler-Coller and Turnbull). The growth fraction showed extreme heterogeneity in the cases examined, within each grade of differentiation.

1974 ◽  
Vol 142 (3) ◽  
pp. 483-489 ◽  
Author(s):  
Barry Lesser ◽  
Nicholas Bruchovsky

The regenerating rat prostate was used as an experimental model to determine the effects of 5α-dihydrotestosterone on certain parameters of cell proliferation, including the duration of the phases of the cell cycle and the size of the cellular growth fraction. Rats castrated 7 days previously were treated with daily subcutaneous injections of 5α-dihydrotestosterone for 14 days; 48h after the beginning of therapy, cells in the process of DNA synthesis were labelled with a single injection of radioactive thymidine and the progress of these cells through the division cycle was observed. Cell-cycle analysis was performed by fractionating prostatic nuclei according to their position in the cell cycle by using the technique of velocity sedimentation under unit gravity. The results indicate that during regeneration the cell population undergoes 1.8 doublings with a doubling time of 40h, and that the process involves almost four rounds of cell division with a cell-generation time of 20h. The growth fraction at any time is about 0.5, and about half the daughter cells produced do not re-enter the proliferative cycle. All cells present at the start of regeneration eventually undergo at least one division during the course of regeneration, although any given cell can divide from one to four times.


1992 ◽  
Vol 6 (6) ◽  
pp. 343-350 ◽  
Author(s):  
Junko Miyachi ◽  
Kazuyuki Doi ◽  
Kazuyuki Kitamura ◽  
Tomofumi Jitsukawa ◽  
Hiroshi Watanabe

1996 ◽  
Vol 44 (11) ◽  
pp. 1261-1265 ◽  
Author(s):  
H Funato ◽  
M Yoshimura ◽  
Y Ito ◽  
R Okeda ◽  
Y Ihara

Here we report on the presence of proliferating cell nuclear antigen (PCNA) in human leptomeninges from 35 normal subjects with ages ranging from 57 to 94 years. Strong immunoreactivity with PC10 (a monoclonal antibody to PCNA) was detected in the nuclei of meningothelial cells, smooth muscle cells of leptomeningeal vessels, and ependymal cells. An immunoblot of leptomeningeal homogenate with PC10 showed the presence of a single band at 35 KD, the expected molecular mass of PCNA. Ki-67, another marker for cell proliferation, was undetectable in human leptomeninges. These observations point to isolated PCNA expression in tissue in which cells are not actively proliferating.


2001 ◽  
Vol 86 (11) ◽  
pp. 5194-5200 ◽  
Author(s):  
Marco Losa ◽  
Enrica Ciccarelli ◽  
Pietro Mortini ◽  
Raffaella Barzaghi ◽  
Daniela Gaia ◽  
...  

To investigate the effects of octreotide administration on the growth rate of GH-secreting pituitary adenomas, we measured both the Ki-67 labeling index (LI) and the apoptotic index in tumor specimens from octreotide-treated or matched untreated acromegalic patients. Thirty-nine patients who received octreotide until the day of or the day before surgery and 39 untreated patients matched for sex, age, tumor size, extension, and invasiveness were studied. Immunocytochemical analysis was performed on paraffin-embedded material using a monoclonal antibody (MIB-1) directed against a proliferation-associated nuclear antigen, Ki-67, to measure the growth fraction. Apoptosis was assessed by the terminal deoxynucleotidyl transferase-mediated deoxy-UTP nick endlabeling method, using a monoclonal antibody recognizing areas of DNA fragmentation. The Ki-67 LI and apoptosis were counted on separate slides in at least 1000 evaluable cells. Octreotide-treated patients showed a lower Ki-67 LI (1.8 ± 0.3%) than untreated controls (3.8 ± 0.7%; P < 0.02). Overall, the mean Ki-67 LI of treated patients was 53% lower than that in untreated patients. The antiproliferative effect of octreotide occurred independently of tumor extension and invasiveness. Octreotide-treated and untreated patients showed similar apoptotic indexes (0.6 ± 0.2% and 0.8 ± 0.3%, respectively). There was a positive correlation between the Ki-67 LI and the apoptotic index (r = 0.29; P< 0.03). Our study demonstrates that acromegalic patients receiving chronic octreotide treatment have a lower value of the proliferation marker Ki-67, but no significant difference in the apoptotic index compared with matched untreated patients. The antiproliferative effect of octreotide on GH-secreting adenomas should imply a lower risk of tumor growth during long-term chronic treatment with the drug.


1994 ◽  
Vol 12 (6) ◽  
pp. 1193-1203 ◽  
Author(s):  
S Welt ◽  
C R Divgi ◽  
A M Scott ◽  
P Garin-Chesa ◽  
R D Finn ◽  
...  

PURPOSE To define the toxicity, imaging, and biodistribution characteristics of iodine 131-labeled monoclonal antibody F19 (131I-mAbF19). MAbF19 recognizes the fibroblast activation protein (FAP), a cell-surface glycoprotein not present in most normal tissues, but abundantly expressed by reactive stromal fibroblasts of epithelial cancers, including more than 95% of primary and metastatic colorectal carcinomas. PATIENTS AND METHODS 131I-mAbF19 was administered intravenously to 17 patients with hepatic metastases from colorectal carcinoma who were scheduled for resection of localized metastases or insertion of hepatic artery catheter for regional chemotherapy. Seven to 8 days before surgery, patients received 131I-mAbF19 at three dose levels, with at least four patients entered at each level. RESULTS No toxicity associated with intravenous 131I-mAbF19 administration was observed. Tumor images were obtained on planar and single-photon emission tomography (SPECT) scans in 15 of 17 patients with hepatic metastases, tumor-infiltrated portal lymph nodes, and/or recurrent pelvic disease. The smallest lesion visualized was 1 cm in diameter. The optimal time for tumor imaging was 3 to 5 days after 131I-mAbF19 administration. The use of image registration techniques allowed precise anatomic localization of 131I-mAbF19 accumulation. Immunohistochemical analysis of biopsy tissues showed expression of FAP in the tumor stroma (but not in normal liver) in all patients studied and confirmed that the FAP-positive tumor stromal fibroblasts were interposed between the tumor capillaries and the malignant colon epithelial cells. At the time of surgery, tumor-to-liver ratios up to 21:1 and tumor-to-serum ratios up to 9:1 were obtained. The fraction of the injected 131I-mAbF19 dose per gram tumor (%ID/g tumor) localized to hepatic metastases at the time of surgery ranged from 0.001% to 0.016%. CONCLUSION The FAP tumor fibroblast antigen is highly expressed in primary and metastatic colorectal carcinomas and shows limited expression in normal adult tissues. This highly selective expression pattern allows imaging of colorectal carcinoma lesions as small as 1 cm in diameter on 131I-mAbF19 scans. Because of the consistent presence of FAP in the stroma of epithelial cancers and the accessibility of FAP-positive tumor stromal fibroblasts to circulating monoclonal antibodies (mAbs), this study suggests possible diagnostic and therapeutic applications of humanized mAbF19 and mAbF19 constructs with novel immune and nonimmune effector functions.


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