We have examined the occurrence of apoptotic cell death in formalin‐fixed, paraffin‐embedded human gastric carcinoma specimens by the terminal deoxynucleotidyl transferase (TdT)‐mediated dUTP‐biotin nick end labeling (TUNEL) method. The specificity of the TUNEL signals was confirmed by the omission of either TdT or biotinylated dUTP as negative controls, and by pretreatment with DNase I as a positive control. Careful observation of routine hematoxylin and eosin‐stained sections showed a few tumor cells with apoptosis, especially in well‐differentiated carcinomas. Intense TUNEL signals were frequently observed even in ordinary, non‐pyknotic nuclei of tumor cells, and occasionally also in nuclear fragments corresponding to apoptotic bodies. Apoptotic indices (number of apoptotic cells/total number of tumor cells) ranged between 7.7 and 14.5% (mean, 10.9%) in nine well‐differentiated carcinomas and between 2.7 and 7.5% (mean, 4.0%) in five which were poorly differentiated, the mean number being significantly higher in the former (P<0.01). No apparent correlation was found between apoptosis and the expression of proliferating cell nuclear antigen, P53 or Ley in the present study. This high frequency of apoptosis, implying cell loss, may be related to the slow‐growing nature of well‐differentiated carcinomas. Poorly differentiated carcinomas, including scirrhous gastric carcinomas, showed a lower incidence of apoptosis, indicating the existence of an escape mechanism from the process.

We examined the occurrence of apoptotic cell death in 15 advanced colorectal carcinomas with lymph-node and/or liver metastases by terminal-deoxynucleotidyl-transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL). TUNELpositive cells were used to quantify the apoptotic index (Al: percentage of TUNEL-positive cells in carcinomatous cells). Similarly, Ki-67-positive cells were used to quantify Ki-67 labeling (KI: percentage of Ki-67-positive cells in carcinomatous cells) as a proliferative index. The mean Als of primary colorectal carcinomas, lymph-node and liver metastases were 3.5%, 5.6% and 6.2% respectively. There was a significant group difference between primary carcinomas and lymph-node or liver metastases. The mean Kls of primary colorectal carcinomas, lymph-node and liver metastases were 5 I .8%, 60. I Yo and 6 I .7% respectively. There was a significant group difference between primary carcinomas and lymph-node or liver metastases. In addition, there was a close positive relationship between the Al and MI per specimen. There was no apparent correlation between Al or MI and the expression of nuclear p53 of cancer cells. These results suggested that cell proliferation and loss (apoptosis) were more frequent in metastatic foci than in primary lesions, and that apoptosis might reflect not only cell loss but also the proliferative activity of human colorectal carcinomas.o 1996 Wiley-Liss, Znc.Apoptosis refers to cell death in which individual cells participate in their own fragmentation and deletion from living tissue (Kerr et af, 1994). It is a basic biological phenomenon of critical importance in the regulation of cell populations in situations as diverse as metamorphosis, embryonic growth and modeling, hormone-induced organ involution and neoplasia. Apoptosis has distinct morphological features, including compacting of chromatin against the nuclear membrane, cell shrinkage with the preservation of organelles, detachment from surrounding cells, and nuclear and cytoplasmic budding to form membrane-bound fragments, known as apoptotic bodies, which are rapidly phagocytosed by adjacent parenchymal cells or macrophages (Kerr et al., 1972).Terminal-deoxynucleotidyl-transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL) has been introduced to detect apoptotic cells in routine formalin-fixed, paraffinembedded sections (Gavrieli et aL, 1992). There are some descriptions of applying this method to rat embryos, human lymph nodes and human gastric carcinomas (Wijsman et al., 1993;Ansari et al., 1993;Kasagi et al., 1994). Cancer cells have a decreased ability to undergo apoptosis in response to at least some physiologic stimuli. The comparative rates of cell proliferation and cell death determine how fast cancer can grow.Here, we analyzed the relationship between proliferation and apoptosis in human colorectal carcinomas with lymphnode and/or liver metastases using TUNEL. Paradoxically, our data suggested that apoptosis might reflect not only cell loss but also the proliferative activity of colorectal...

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Characteristics of mouse macrophage (MP) cell lines A640-BB-2, J774.1 and P388D1 and mouse peritoneal exudate MPs were studied and compared in cell morphology, ability to recognize tumor cells in the presence and absence of OK-432 known to activate MPs, and in lysosomal enzyme activity. In A640-BB-2 cells and exudate MPs, cell surfaces showed a few ridge-like processes and microvilli; spontaneous cytotoxicity was moderate against tumor target L929, and little or absent against targets SV3T3, B-16 and U937; and lysosomal enzyme activity of nonspecific esterase, acid phosphatase, and beta-glucuronidase was high. After culture in the presence of OK-432, A640-BB-2 cells and exudate MPs showed more extensive spreading with larger surface areas and with increased numbers of ridge-like processes and microvilli, and their cytotoxicity against target L929 became more extensive. The stable soluble factor did not participate in the mechanism of cytotoxicity against target L929 mediated by A640-BB-2 cells and exudate MPs. J774.1 and P388D1 cells were different from exudate MPs in cell morphology and ability to recognize tumor cells when cultured either with or without OK-432, and in lysosomal enzyme activity. A640-BB-2 cells seem to be useful in studying MP-tumor cell interaction and MP activation, and in detecting the trace biological activating factor of MPs.

There is only one report of patients with developmental delay due to a 6q16.1 deletion that does not contain the SIM1 gene. A 3-year-old female showed strabismus, cleft soft palate, hypotonia at birth, and global developmental delay. Exome sequencing detected a de novo 6q16.1 deletion (chr6: 99282717–100062596) (hg19). The following genes were included in this region: POU3F2, FBXL4, FAXC, COQ3, PNISR, USP45, TSTD3, CCNC, and PRDM13.