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Biomedical subjects

M Imamura

Publications and source records attributed to M Imamura.

At least 127 records · Page 7Linked to original sources
PubMed2000

Nuclear transfer in cattle using colostrum-derived mammary gland epithelial cells and ear-derived fibroblast cells.

To assess the developmental potential of nuclear transfer embryos in cattle using mammary gland epithelial (MGE) cells derived from the colostrum, we compared the effectiveness of cloning using those cells and fibroblast cells derived from the ear. The fusion rate of the enucleated oocytes with fibroblast cells (75 +/- 4%) was significantly higher than that with MGE cells (56 +/- 7%, P<0.05). There were no significant differences in the cleavage rate (85 +/- 3% vs. 91+/- 2%) or in the developmental rate to the blastocyst stage (35 +/- 6% vs. 35 +/- 5%) using MGE cells vs. fibroblast cells as donor nuclei (P>0.05). After transfer of blastocysts derived from nuclear transfer embryos produced using MGE cells and fibroblast cells, 13% (4/31) and 16% (6/37) of recipient heifers were pregnant on Day 42 as assessed by ultrasonography, respectively. Two of the 4 and 4 of the 6 recipients of embryos with MGE cell- and fibroblast cell-derived nuclei, respectively, aborted within 150 days of pregnancy. Four live female calves were obtained from MGE cells or fibroblast cells. However, one died from internal hemorrhage of the arteria umbilicalis. The other three calves were normal and healthy. There were no differences in the pregnancy rate or calving rate when using MGE cells vs. fibroblast cells. Microsatellite DNA analyses confirmed that the cloned calves were genetically identical to the donor cows and different from the recipient heifers. We conclude that colostrum-derived MGE cells have the developmental potential to term by nuclear transfer, and the efficiency of development of those cloned embryos was the same as that of embryos obtained using fibroblast cells as donor nuclei, although there was a significant difference in the fusion rate. This method using MGE cells derived from colostrum, which is obtained easily and safely from live adult cows, is more advantageous for cloning with somatic cells.

Animals↗
PubMed2000

Combination therapy with transcatheter arterial chemoembolization and percutaneous microwave coagulation therapy for hepatocellular carcinoma.

BACKGROUND: A small number of microwave electrode insertions and microwave irradiations were used to obtain complete tumor necrosis in hepatocellular carcinomas (HCC) measuring > 2.0 cm but </= 3.0 cm in greatest dimension. The efficacy of combining transcatheter arterial chemoembolization (TACE) with subsequent percutaneous microwave coagulation therapy (PMCT) was assessed in this study. METHODS: Eighteen patients with cirrhosis and HCCs measuring > 2.0 cm but </= 3.0 cm in greatest dimension underwent TACE followed within 1-2 days by ultrasonographically guided PMCT. RESULTS: On dynamic computed tomography, 17 of the 18 patients showed complete necrosis of their tumor lesions and the treated tumor margins (>/= 5 mm). Necroses of tumors and noncancerous margins surrounding the tumors were obtained using 4 microwave irradiations (1 session) in 14 patients, 5 microwave irradiations (2 sessions) in 2 patients, and 6 microwave irradiations (2 sessions) in 1 patient. The follow-up period was short (12-31 mos), and all patients remained alive. No local recurrences in the treated areas were detected. No fatal complications were observed. Pleural effusion was observed in 1 patient only. CONCLUSIONS: This combined therapy of PMCT applied within 1-2 days of TACE effectively treated HCCs measuring > 2.0 cm but </= 3.0 cm in greatest dimension. A small number of microwave electrode insertions and microwave irradiations were used.

Aged↗
PubMed2000

Role of E-cadherin in peritoneal dissemination of the pancreatic cancer cell line, panc-1, through regulation of cell to cell contact.

The present study was designed to clarify the molecules responsible for peritoneal dissemination of cancer cells. We established sublines with high (HP cells) and low (LP cells) passing activity through the membrane of a transwell chamber. The cell lines were established from the human pancreatic cancer cell line, Panc-1. LP cells demonstrated an octagonal shape and tight adhesion, whereas HP cells exhibited a spindle shape and grew with less cell-cell contact in vitro. It was found that HP cells demonstrated a high degree of peritoneal dissemination in nude mice following peritoneal injection of these cells compared to LP cells. We subsequently investigated the expression of certain adhesion molecules. Consequently, we found that LP cells exhibited a stronger expression of E-cadherin than HP cells. On the other hand, there was no difference in the expression of CD44H and beta1 integrin between these two sublines. Passing activity of LP cells through the membrane of the invasion chamber increased to nearly equal levels with HP cells following treatment with anti-human E-cadherin antibody. Moreover, transfection of mouse E-cadherin cDNA into HP cells reduced both passing activity through the membrane of the invasion chamber and peritoneal dissemination in nude mice to levels similar to that of LP cells. In conclusion, these results indicated that loss of E-cadherin facilitates both passing activity in an invasion chamber and peritoneal dissemination, playing a causative role in peritoneal dissemination of cancer cells.

Animals↗
PubMed2000

Spleen-derived dendritic cells engineered to enhance interleukin-12 production elicit therapeutic antitumor immune responses.

The major goal in cancer immunotherapy is the induction of tumor-specific T lymphocytes capable of killing tumor cells. As both dendritic cells (DCs) and interleukin-12 (IL-12) can play immunostimulatory roles in vivo, the use of a combination of these has become a promising approach. In the present study, we used a murine tumor model to examine whether spleen-derived DCs transduced with the IL-12 gene could elicit tumor-specific immune responses. BALB/c mice injected peritumorally with adenovirus-mediated IL-12 gene-transduced antigen-unpulsed DCs inhibited the growth of day 5-established subcutaneous CT26 tumors. Splenocytes from treated mice responded specifically to parental tumor cells and showed increased production of interferon gamma (IFN-gamma) and antitumor cytotoxic T-lymphocyte (CTL) activity. Increased numbers of both CD4(+) and CD8(+) T cells were detected in the treated tumors. The inhibition of tumor growth was significantly greater in mice injected with IL-12 gene-transduced DCs than in those injected with IL-12 gene-transduced fibroblasts or the IL-12 gene-encoding adenovirus itself. Taken together, these results indicate that DCs transduced with the IL-12 gene by a recombinant adenovirus are effective in inducing tumor-specific Th1 and CTL responses that inhibit the growth of established subcutaneous tumors.

Adenocarcinoma↗
PubMed2000

Identification of a novel gene, GASC1, within an amplicon at 9p23-24 frequently detected in esophageal cancer cell lines.

In a recent study, we identified frequent amplification of DNA copy number at chromosome 9p23-24 in cell lines derived from esophageal squamous cell carcinomas (ESCs), using comparative genomic hybridization. Because amplified regions often harbor oncogenes and/or other tumor-associated genes, and because 9p23-24 amplification had been reported in various other types of cancers, we used fluorescence in situ hybridization and Southern blot analysis to map the 9p23-24 amplicon. We then screened target genes/transcripts present within this amplicon by Northern blotting. With this strategy, we successfully cloned a novel gene, designated gene amplified in squamous cell carcinoma 1 (GASC1), that was amplified and overexpressed in several ESC cell lines. The deduced amino acid sequence of GASC1 contains two PHD-finger motifs and a PX domain. PHD-finger motifs are found in nuclear proteins that participate in chromatin-mediated transcriptional regulation and are present in a number of proto-oncogenes. Our findings suggest that overexpressed GASC1 may play an important role in the development and/or progression of various types of cancer including ESC.

Amino Acid Sequence↗
PubMed2000

Loss of fragile histidine triad gene expression is associated with progression of esophageal squamous cell carcinoma, but not with the patient's prognosis and smoking history.

BACKGROUND: Recently, fragile histidine triad (FHIT) gene abnormality has been thought to be associated with several malignancies and smoking history. The authors previously discovered that methylation of the 5' CpG island of the FHIT gene was closely associated with transcriptional inactivation in esophageal squamous cell carcinoma (SCC); however, the clinical impact of the FHIT gene in esophageal carcinoma is still unknown. METHODS: In this article, the authors evaluated the clinical impact of the FHIT gene in 149 esophageal squamous cell carcinoma (SCC) patients retrospectively using immunohistochemical analysis. They also examined the correlation between FHIT protein expression and smoking history. RESULTS: Among 149 curative resection (R0) cases of esophageal SCC, normal FHIT protein expression was noted in only 33 cases (22.1%), whereas reduced FHIT protein expression was noted in 67 cases and there was no FHIT expression in 50 cases. When a tumor invaded the muscle layer, FHIT protein expression was markedly reduced. The cases with reduction or loss of FHIT protein expression tended to have poor prognoses (P = 0.069). However, Cox multivariate analysis revealed that FHIT protein reduction had no relation to prognosis. FHIT protein expression had no relation to smoking history. CONCLUSIONS: FHIT protein expression was associated with progression of esophageal SCC, however, it may not be associated with the patient's prognosis and smoking history.

Aged↗
PubMed2000

Implication of vascular endothelial growth factor and p53 status for angiogenesis in noninvasive colorectal carcinoma.

BACKGROUND: It still is unclear when angiogenic potential, which is believed to be a prerequisite for tumor development, is acquired. The current study was designed 1) to clarify when the phenotypic change of angiogenicity occurs during the development of colon carcinoma and 2) to investigate the possible roles of vascular endothelial growth factor (VEGF) and p53 in angiogenesis. METHODS: Colon carcinomas were classified according to the following criteria: m carcinomas were tumors in which carcinoma cells were observed within the mucosa (excluding adenomas with severe atypia) according to the World Health Organization criteria. sm carcinomas were defined by invasion into the submucosa but not into the muscularis propria. Using 27 adenomas, 26 m carcinomas, and 20 sm carcinomas, VEGF expression was analyzed with reverse transcriptase-polymerase chain reaction and immunohistochemistry. Microvessel density, VEGF, and p53 status were evaluated by immunohistochemistry. RESULTS: Neither VEGF mRNA nor VEGF protein was detected in any of the mild-to-moderate dysplastic adenomas, whereas 16 of 26 m carcinomas (62%) and all sm carcinomas exhibited VEGF protein. The microvessel density in adenomas, m carcinomas, and sm carcinomas was 3 +/- 0.55, 6.1 +/- 1.12, and 12 +/- 1.35 (0.739 mm(2) per field), respectively. In m carcinomas, positive VEGF expression was coincident with the expression of p53, and stainability for both VEGF and p53 was similar with regard to spatial distribution in tumor tissues. In m and sm carcinomas, there was a statistically significant correlation between the intensity of VEGF expression and microvessel density. CONCLUSIONS: The results of the current study demonstrated that angiogenesis develops in association with tumor progression from adenoma to noninvasive colorectal carcinoma, at least in part due to VEGF, and suggested that VEGF in m carcinomas is induced by mutant p53, although alternative mechanisms of VEGF up-regulation may exist in sm carcinomas.

Adenoma↗
PubMed2000

Biochemical evidence for association of dystrobrevin with the sarcoglycan-sarcospan complex as a basis for understanding sarcoglycanopathy.

The sarcoglycan complex is composed of four membrane-spanning dystrophin-associated proteins (DAPs) and is essential for skeletal muscle survival, since the absence or markedly reduced expression of this complex due to mutation of any one of the sarcoglycan genes causes a group of muscular dystrophies, collectively termed sarcoglycanopathy. Although one of the putative functions of the sarcoglycan complex is its participation in signaling processes, detailed studies have been scarce. Very recently, it was shown that gene knockout mice for a DAP, alpha-dystrobrevin, exhibit a dystrophic phenotype, possibly due to defects in muscle cell signaling. To clarify the putative function of the sarcoglycan complex, it is essential to determine whether or not there is a link between it and the intracellular signaling molecules. To elucidate this, we developed new methods for preparing various DAP complexes containing the sarcoglycan complex from the purified dystrophin-DAP complex. It was suggested from one of the complexes prepared that the sarco-glycan-sarcospan complex (the sarcoglycan complex associated with sarcospan) is associated with syntrophin and/or dystrobrevin. Further analysis of this complex revealed that the N-terminal half of dystrobrevin participates in this association. It is thus considered that the sarcoglycan-sarcospan complex is linked to the signaling protein neuronal nitric oxide synthase via alpha-syntrophin associated with dystrobrevin.

Animals↗
PubMed2000

Unique clinical characteristics of patients with hepatocellular carcinoma who present with high plasma des-gamma-carboxy prothrombin and low serum alpha-fetoprotein.

BACKGROUND: Although the importance of alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) in the clinical treatment of hepatocellular carcinoma (HCC) has been studied extensively, the authors examined the clinical picture of HCC with regard to the state of these two tumor markers. METHODS: The authors categorized 237 HCC cases into 4 groups according to levels of AFP and DCP: high levels of AFP with low DCP levels, high DCP levels with low AFP levels, high levels of both tumor markers, and low levels of both tumor markers. Comparisons of survival rates were made among these groups using the Kaplan-Meier product limit method, and for other comparisons of clinical parameters the Fisher PSLD test was used. Prognostic significance was tested with the Cox proportional hazards model. RESULTS: The cutoff values were set at 100 ng/mL for AFP and 0.0625 AU/mL for DCP. Forty-eight patients (20.7%) had high levels of AFP and low levels of DCP, 22 (9.3%) had high DCP levels and low levels of AFP, 12 (4.6%) had high levels of both AFP and DCP, and 155 (65.4%) had low levels of both DCP and AFP. Patients with high levels of DCP but low levels of AFP were predominantly male and had large lesions but few nodules. Patients with high levels of both tumor markers had the most discouraging outcome observed in this study (death within 3 years). CONCLUSIONS: Patients with high levels of DCP and low levels of AFP exhibited the unique clinical characteristic of large HCC nodules that were few in number. In addition, it was observed that measurement of both AFP and DCP can predict the survival of patients.

Adult↗
PubMed2000

[The long-term perfusion system on amylase release from dispersed acinar cells--comparative study with direct incubation techinique and residual stimulation].

We have modified the perfused guinea pig pancreatic acini system in order to obtain reproducible results in repeated secretagogue stimulation. No signs of tachyphylaxis were observed when cholecystokinin-8 (CCK-8) was administered as short pulse for 5 minutes and the interval between administrations were kept more than 90 minutes. Maximal amylase response was obtained at 10(-8) M of CCK-8 and a supra-maximal significant inhibition on amylase release was observed with higher doses of CCK-8. Twenty minutes stimulation with 10(-8) M of CCK-8 showed a biphasic response; while, 5 minutes stimulation showed a mono-phasic pattern. The results suggest that amylase response was highly influenced not only by the concentration of the secretagogue but also the duration of the stimulation in this perfusion system. The mechanism of this phenomenon may be comprehensive by the double-ligand-complex theory based on low and high affinity site on cell surface receptors.

Amylases↗
PubMed2000

The suppression of small GTPase rho signal transduction pathway inhibits angiogenesis in vitro and in vivo.

Angiogenesis consists of multistep pathways such as the degradation of the matrix, proliferation of the endothelial cells, motility of the endothelial cells, formation of the cord structure and network formation of microvessels. The small GTPase Rho participates in cell motility through actin fiber polymerization. The role of the small GTPase Rho signal transduction pathway in regulating angiogenesis, however, is still unknown. In this study, we investigated the role of the small GTPase Rho signal transduction pathway in angiogenesis in vitro and in vivo using the exoenzyme, Clostridium botulinum C3 transferase, which specifically suppresses Rho and a compound, Y-27632, which suppresses p160ROCK (Rho-associated coiled-coil containing protein kinase). In this paper, we showed that the small GTPase Rho-p160ROCK signal transduction pathway played an important role in angiogenesis both in vitro and in vivo. These results suggest that inhibition of the small GTPase Rho signal transduction pathway by the p160ROCK inhibitor could be a possible new strategy for angiogenic diseases.

Amides↗
PubMed2000

Tissue factor expression in human colorectal carcinoma: correlation with hepatic metastasis and impact on prognosis.

BACKGROUND: It has been suggested that tissue factor (TF) plays an important role in tumor metastasis. Its expression in sarcoma cells was reported to up-regulate the vascular endothelial growth factor (VEGF) gene and thereby enhance tumor angiogenesis, which is essential to tumor metastasis. Although many malignant tumors have been reported to express this protein constitutively, recent clinical studies have focused mainly on the correlations among TF expression, tumor progression, and histologic grade. Therefore, to address the role of TF and the underlying mechanism of hematogenous metastasis of colorectal carcinoma, the authors analyzed the correlations among TF expression, hepatic metastasis, and VEGF gene expression in surgical specimens. Furthermore, they analyzed the prognostic significance of TF expression with respect to overall patient survival. METHODS: Expression of TF and VEGF genes in 67 advanced colorectal carcinoma specimens was studied by immunohistochemistry and Northern blot analysis, respectively. The correlations among TF expression, hepatic metastasis, and other factors were analyzed with univariate and multivariate statistics. Survival rates were calculated using the Kaplan-Meier method. RESULTS: Univariate and multivariate analyses showed TF expression to be a significant (P = 0.0001) and independent risk factor for hepatic metastasis, whereas a weak but insignificant correlation was observed between TF and VEGF gene expression. The outcomes in the TF positive group were significantly worse in all cases (P = 0.0001) and in the cases without synchronous hepatic metastasis (P = 0.0156). CONCLUSIONS: Although the precise mechanisms are unknown, TF expression is a suitable indicator of both hepatic metastasis and prognosis for colorectal carcinoma patients.

Aged↗
PubMed2000

Protection by vascular endothelial growth factor against sinusoidal endothelial damage and apoptosis induced by cold preservation.

BACKGROUND: It is well known that sinusoidal endothelial cell (SEC) damage during cold preservation of liver tissue is closely involved in early graft failure. The objective of this study was to investigate the involvement of apoptosis in the SEC damage induced by cold preservation and to demonstrate the protective effect of vascular endothelial growth factor (VEGF) on SEC injury, including apoptotic changes. METHODS: Isolated SECs and liver tissue of Wistar rats were cold-preserved in University of Wisconsin (UW) solution, and the protective effect of VEGF was then investigated. Isolated SECs were cultured for 24 hr, and divided into the following 3 groups: Group A, in which the cells were cultured for an additional 27 hr, Group B, in which the cells were cold-preserved in UW solution for 3 hr, and then recultured for 24 hr, and Group C, in which 20 ng/ml of VEGF was added to both the culture medium and the UW solution of cells cultured according to the Group B protocol. Each group of SECs was morphologically examined using the phase contrast microscopic method and the transmission electron microscopic method (TEM), and quantitatively analyzed using the WST-1 assay. Rat livers were cold-preserved in UW solution and divided into the VEGF(+) group and the VEGF(-) group, depending on whether VEGF was added or not. Each group of livers were analyzed by scanning electron microscopic method (SEM) after 24 hr of preservation. The hyaluronic acid uptake rate (HUR) was also determined after 6 hr of preservation. After 24 hr of preservation and 6 hr of reperfusion, tissues were examined by TEM and by the terminal deoxynucleotidyl transferase d-uridine triphosphate nick end labeling (TUNEL) assay. RESULTS: The phase contrast microscopic method and the WST-1 assay showed a protective effect of VEGF against the injury to isolated SECs during cold preservation and subsequent reculturing. Apoptosis was detected immediately by TEM after isolation of SECs, and the number of apoptotic cells increased with the incubation time. This increase was accelerated after cold preservation. The scanning electron microscopic method and the hyaluronic acid uptake rate showed a protective effect of VEGF against SEC damage in the cold-preserved livers. In the liver tissue, the TEM and the TUNEL assay detected apoptosis of SECs only after cold preservation and subsequent reperfusion. VEGF suppressed the apoptosis of SECs induced by cold preservation in both isolated cells and liver tissue. CONCLUSIONS: We demonstrated that SEC damage in the cold preservation of liver tissue was caused mainly by apoptosis, which required subsequent reperfusion. Moreover, isolated SECs showed spontaneous occurrence of apoptotic changes during culture, and these changes were accelerated by the preceding cold preservation. This is the first report to demonstrate the apoptotic changes of SECs seen here were inhibited by VEGF.

Animals↗
PubMed2000

Stable transfectants of smooth muscle cell line lacking the expression of myosin light chain kinase and their characterization with respect to the actomyosin system.

We constructed a plasmid vector having a 1.4-kilobase pair insert of myosin light chain kinase (MLCK) cDNA in an antisense direction to express antisense mRNA. The construct was then transfected to SM3, a cell line from vascular smooth muscle cells, producing a few stable transfectants. The down-regulation of MLCK expression in the transfectants was confirmed by both Northern and Western blots. The control SM3 showed chemotaxic motility to platelet-derived growth factor-BB, which was supported by lamellipodia. However, the transfectants showed neither chemotaxic motility nor developed lamellipodia, indicating the essential role of MLCK in the motility. The specificity for the targeting was assessed by a few tests including the rescue experiment. Despite this importance of MLCK, platelet-derived growth factor-BB failed to induce MLC20 phosphorylation in not only the transfectants but also in SM3. The mode in which MLCK was involved in the development of membrane ruffling is discussed with special reference to the novel property of MLCK that stimulates the ATPase activity of smooth muscle myosin without phosphorylating its light chain (Ye, L.-H., Kishi, H., Nakamura, A., Okagaki, T., Tanaka, T., Oiwa, K., and Kohama, K. (1999) Proc. Natl. Acad. Sci. U. S. A. 96, 6666-6671).

Actomyosin↗
PubMed2000

Comparison of short inversion time inversion recovery (STIR) and fat-saturated (chemsat) techniques for background fat intensity suppression in cervical and thoracic MR imaging.

The purpose of this study was to compare short inversion time inversion recovery (STIR) fast spin-echo (FSE), and fat-saturated T2-weighted FSE sequences in terms of uniformity of fat suppression and lesion conspicuity for magnetic resonance (MR) imaging of the neck and thorax. STIR FSE and fat-saturated T2-weighted FSE images were scored for uniformity of fat suppression (n = 40) and lesion conspicuity (n = 35). Five-point rank score analyses were utilized by three experienced radiologists. The mean scores of STIR and fat-saturated FSE techniques for uniformity of fat suppression were 4.3 and 2.3, respectively (P < 0.0001). The mean scores of STIR and fat-saturated FSE techniques for lesion conspicuity were 4.2 and 3.5, respectively (P < 0.0001). Insufficient fat suppression was prominent in the mandible, supraclavicular region, anterior mediastinum, epipericardial fat, and subdiaphragmatic fat. In addition, fat-saturated T2-weighted FSE showed inadvertent water suppression in 25%. The STIR FSE technique was superior to the fat-saturated FSE technique for cervical and thoracic MR imaging.

Adolescent↗
PubMed2000

Massage for low back pain.

BACKGROUND: Low back pain is one of the most common and costly musculoskeletal problems in modern societies. Proponents of massage therapy claim it can minimize pain and disability, and speed return to normal function. OBJECTIVES: To assess the effects of massage therapy for non-specific low back pain. SEARCH STRATEGY: We searched Medline, Embase, Cochrane Controlled Trials Register, Healthstar, CINAHL and Dissertation abstracts from 1966 to 1999 with no language restrictions. References in the included studies and in reviews of the literature were also screened. Contact with content experts and massage associations were also made. SELECTION CRITERIA: This review included randomized, quasi-randomized or controlled clinical trials that investigated the use of any type of massage (using the hands or a mechanical device) as a treatment for nonspecific low back pain. DATA COLLECTION AND ANALYSIS: One reviewer applied the selection criteria and extracted the data. Two reviewers (one blinded to authors, institutions and journals) independently assessed the quality of each trial. A qualitative analysis (best-evidence synthesis) was performed due to clinical heterogeneity among the included trials and insufficient data reported. MAIN RESULTS: Four randomized controlled trials met the inclusion criteria. Two trials were of high and two of low methodological quality. None evaluated massage as the main intervention. Rather, it was the control intervention in studies evaluating manipulation, electrical stimulation, and a lumbar corset. There is limited evidence showing that massage is less effective than manipulation immediately after the first session and moderate evidence showing it is less effective than TENS during the course of sessions in relieving pain and improving activity. At the completion of treatment and at 3 weeks after discharge there is no difference among massage and manipulation, electrical stimulation or corsets, but this evidence is limited. REVIEWER'S CONCLUSIONS: Based on the studies reviewed, there is insufficient evidence to recommend massage as a stand-alone treatment for non-specific low back pain. There is a need for high quality controlled trials to further evaluate the effects of massage for this condition.

Adult↗
PubMed2000

Pathologic significance of tumor progression in locally recurrent rectal cancer: different nature from primary cancer.

PURPOSE: It has recently been demonstrated that the tumor growth rate is a stronger determinant of survival than the extent of the growth in local recurrence of rectal cancer. We studied which factors controlled the tumor growth rate using modern immunohistochemical methods. METHODS: In 51 patients who underwent extended resection for this condition, paraffin-embedded specimens were examined for 1) tumor angiogenesis by CD31 staining and microvessel counting, 2) apoptosis by terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling staining, and 3) cellular proliferative activity using anti-proliferative cell nuclear antigen antibody. The results were compared with carcinoembryonic antigen doubling time and survival. RESULTS: The five-year survival rate was 20 percent. The postoperative carcinoembryonic antigen doubling time, which was the strongest predictor of survival, correlated highly with proliferative cell nuclear antigen labeling index, but did not correlate with the apoptotic index or microvessel counts. CONCLUSION: Our study shows that cancer cell proliferation rather than apoptosis or angiogenesis is a major determinant of tumor growth rate and survival in patients with locally recurrent rectal cancer.

Adult↗