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Biomedical subjects

M Ikeguchi

Publications and source records attributed to M Ikeguchi.

At least 37 records · Page 2Linked to original sources
PubMed2001

Bax expression as a prognostic marker of postoperative chemoradiotherapy for patients with esophageal cancer.

Postoperative chemoradiotherapy was introduced to improve the survival of patients with esophageal squamous cell carcinoma (ESCC). However, considerable number of patients still die of cancer recurrence despite curative operation plus chemoradiotherapy. This indicates that some ESCCs are chemoradio-resistant. To prevent unnecessary treatment and to improve the effect of post-operative adjuvant therapy, it seems to be important to investigate biological markers of chemoradio-sensitivity in ESCC. Loss of Bax expression has been reported to be associated with poor response to chemotherapy in breast cancer, and Bax promotes apoptosis in cells. Abnormal expression of Bax may play an important role in chemoradio-sensitivity in malignant tumors. In this study, we retrospectively investigated the prognostic significance of the expressions of Bax and p53 in patients with ESCC. Immunoreactivities of Bax and p53 were evaluated in 141 surgically resected ESCC by using monoclonal antibodies. Prognoses of 141 patients with or without postoperative chemoradiotherapy were compared among groups with high and low expressions of Bax or p53. High immunoreactivities of Bax and p53 were detected in 49 cases (33.1%) and in 70 cases (47.3%), respectively. Loss of Bax expression was detected more frequently in p53-positive tumors. Bax expression correlated with favorable prognosis (P=0.016) in 57 patients with postoperative chemoradiotherapy. However, in 84 patients without adjuvant therapy, the prognostic significance of Bax was minimal. Moreover, in patients with or without postoperative chemoradiotherapy, p53 expression did not correlate with the prognosis. Bax expression may be a good marker for chemoradio-sensitivity in patients with ESCC.

Aged↗
PubMed2001

Changes in survivin messenger RNA level during cisplatin treatment in gastric cancer.

Survivin is a member of the inhibitor of apoptosis protein (IAP) family. The expression of survivin has not been reported in differentiated normal tissues, but it has been observed in many cancerous tissues. Recent studies have revealed that survivin may correlate with the chemo-radio resistance of certain malignant cells. In the present study, the correlation between the occurrence of apoptosis and the level of expression of survivin messenger RNA (mRNA) was investigated in a gastric cancer cell line (MKN-45) and in patients with advanced gastric cancer during cisplatin (CDDP) treatment. In the gastric cancer cell line, the percentage of apoptotic cells (apoptotic index: AI) did not change after 48 h incubation with low-dose CDDP (1 microg/ml), whereas the AI explosively increased between 12 and 24 h treatment with high-dose CDDP (10 microg/ml). Relative levels of expression of survivin mRNA and survivin protein increased after low- and high-dose CDDP treatment. Survivin mRNA was not detected in normal gastric mucosas. Also, in 13 patients with advanced gastric cancer who underwent CDDP-based preoperative chemotherapy, survivin mRNA was detected in only 2 cases (15.4%). Survivin mRNA was observed in the resected tumor specimens of two cases. No significant correlation between survivin mRNA expression and the occurrence of apoptosis in resected tumors or between survivin mRNA expression and patient survival was observed. These findings indicate that survivin may play an important role for the chemoresistance of this cancer cell line. However, the clinical importance of survivin expression remains unclear in patients with gastric cancer.

Adult↗
PubMed2001

Correlation between spontaneous apoptosis and the expression of angiogenic factors in advanced gastric adenocarcinoma.

The aim of this study was to investigate whether angiogenic factors influence the occurrence of spontaneous apoptosis in advanced gastric cancer. The apoptotic indices (AIs) of 97 tumors from 97 patients with advanced gastric cancer (pT3, pN0, pM0, Stage II) were analyzed by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick end labeling (TUNEL) method. Intratumoral microvessel densities (IMVDs) of tumors stained with anti-CD34 monoclonal antibody were quantified under x 200 magnification using computer-assisted image analysis. The expressions of angiogenic factors, such as vascular endothelial growth factor (VEGF), thymidine phosphorylase (dThdPase), transforming growth factor-alpha (TGF-alpha), and p53 were analyzed immunohistochemically and compared with IMVDs and AIs. The mean IMVD of the 97 tumors was 365/mm2 (range 147-990/mm2). The mean AI of tumors was 2.1% (range 0-11.3%). A significant inverse correlation between the AIs and the IMVDs was shown (p = -0.278, P = 0.0064). The mean IMVDs of tumors with high expressions of dThdPase, TGF-alpha, or p53 were significantly higher than those of tumors with low expressions of these factors. The mean AI of tumors with high expressions of dThdPase was significantly lower than that of tumors with low expressions of dThdPase (P = 0.023). However, no significant correlations were detected between AIs and the expression levels of VEGF, TGF-alpha, or p53. In gastric cancer, dThdPase may play an important role in tumor progression by increasing microvessels and by suppressing apoptosis of cancer cells.

Adenocarcinoma↗
PubMed2001

[Immunohistochemical study of dihydropyrimidine dehydrogenase (DPD) and p53 in biopsied specimens of esophageal cancer before chemoradiotherapy].

We studied whether the immunohistochemical status of dihydropyrimidine dehydrogenase (DPD) and p53 can be used to predict the sensitivity to chemoradiotherapy (CRT) in patients with esophageal cancer. In 19 patients who did not undergo preoperative CRT, the immunoreactivity of DPD and p53 in biopsied specimens correlated well with those in surgically resected specimens (DPD: 100%, p53: 73%). Fifteen patients were treated with 5-FU (250-300 mg/body/day: day 1-5, 8-12), low-dose cisplatin (10 mg/body/day: day 1, 8) and radiotherapy (30-40 Gy). The response rate (CR + PR) for CRT in these patients was 40%. All tumors that showed CR or PR demonstrated low expression of DPD. However, all tumors with high DPD expression showed MR or NC. However, the expression of p53 did not correlate with the response rate for CRT. Therefore, the effect of CRT for esophageal cancer may be predicted by immunohistochemical examination of DPD in biopsied tumor specimens.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

Cisplatin combined with prostaglandin E1 chemotherapy in rat peritoneal carcinomatosis.

Cisplatin intraperitoneal (i.p.) chemotherapy is frequently performed for patients with peritoneal carcinomatosis. However, cisplatin penetrates only the surface of the peritoneal tumor and has serious side effects on renal cells. Thus, cisplatin i.p. chemotherapy had been limited to use for these patients. Prostaglandin E1 (PGE1) has been used for reducing the toxic effects of anticancer drugs because of its cytoprotective effects and has been reported to enhance tumoricidal activity of anticancer drugs. In our study, the effects of PGE1 on the rat peritoneal carcinomatosis model treated with cisplatin i.p. chemotherapy were evaluated. Cisplatin (5 mg/kg) was given in an i.p. administration to 70 tumor-free rats. PGE1 was administered to 35 rats through the tail vein at an infusion rate of 0.1 microg/kg/min (1 ml/hr), and the remaining 35 rats were injected with physiological saline. Forty rats were given an i.p. injection of 1 x 10(7) AH100B cells. Ten days after injection, cisplatin (5 mg/kg) was administered with PGE1 to 20 and the remaining 20 were injected with physiological saline. The accumulation of platinum in the tissues and apoptotic renal cells were analyzed. The maximum concentrations of platinum in the kidneys of PGE1 untreated rats (tumor-free: 10.11 microg/g; tumor-bearing: 11.45 microg/g) did not differ from those of platinum in the kidneys of PGE1-treated rats (tumor-free: 10.28 microg/g; tumor-bearing: 13.28 microg/g). The number of apoptotic renal cells was significantly reduced by PGE1 administration in both tumor-free and tumor-bearing rats. Moreover, PGE1 increased the maximum platinum concentration in tumor masses (5.31 microg/g) of the treated group compared with that in tumor mass of the control group (2.72 microg/g, p = 0.009). These results indicate that PGE1 may increase the anticancer effect of cisplatin by increasing tumor platinum concentration and may reduce the chance of cisplatin-induced renal failure. Intraperitoneal cisplatin chemotherapy combined with PGE1 treatment may have a therapeutic benefit for patients with peritoneal carcinomatosis.

Alprostadil↗
PubMed2000

Molten globule structure of equine beta-lactoglobulin probed by hydrogen exchange.

The molten globule structure of equine beta-lactoglobulin has been inferred from the hydrogen exchange protection of the backbone amide protons. In order to make it possible to measure the hydrogen exchange kinetics of the individual backbone amide protons, the uniformly (15)N-labeled recombinant protein was expressed in Escherichia coli and the NMR peak assignment was obtained for most of the backbone protons. The chemical shift and NOE results obtained under the condition where the protein assumes the native structure are fully consistent with the known secondary structure of bovine beta-lactoglobulin, indicating that the equine protein has a similar native conformation to that of the bovine protein. The hydrogen exchange rate of the individual backbone amide protons was measured under the conditions where the protein assumes the native and molten globule states. In the native state, strong protection was observed for the residues located in the eight (A to H) strands, which form a barrel structure, and residues of a major helix. In the molten globule state at acidic pH conditions, significant protection from the exchange has been observed for residues located in the A, F, G and H strands in the native structure. The pattern of protection is consistent with a native-like beta-sheet formation by these strands. The residues located in a major helix of the native structure are also protected, suggesting that this helix is formed in the molten globule and is packed against the sheet as in the native structure. These results indicate that a native-like subdomain is formed in the molten globule state of equine beta-lactoglobulin.

Amides↗
PubMed2000

Afferent and efferent excitabilities of the transcortical loop in patients with dentatorubral-pallidoluysian atrophy.

To evaluate the excitabilities of the transcortical loop in patients with dentatorubral-pallidoluysian atrophy (DRPLA), we studied somatosensory evoked potentials (SEPs) and evoked EMG responses (V1 and V2) in 10 patients and age-matched controls. In addition, the facilitatory effects of somatosensory inputs on motor evoked potentials (MEPs) were studied in four patients and controls. We observed attenuated or prolonged cervical and subcortical potentials and prolonged middle latency components of SEPs. The amplitudes of V2 in patients were significantly lowered compared to those in the controls, while the amplitudes and latencies of V1 were similar between the two groups. Since V2 was considered as a transcortical reflex, our results suggest reduced excitabilities of the afferent pathway of the transcortical loop in patients with DRPLA. Median nerve stimulation (MNS) 25 to 30 ms preceding transcranial magnetic stimulation (TMS) facilitated MEPs in the thenar muscle in two of the four patients and in the controls. The facilitation of MEPs by MNS tended to be independent of the reduction in V2. Such a result suggests that different neural mechanisms elicit V2 and facilitate MEPs following peripheral nerve stimulation, although further studies are needed. The combination of SEPs, evoked EMG responses and MEPs may be a useful technique to detect abnormalities of input and output coordinations of the transcortical loop.

Adolescent↗
PubMed2000

Clinical significance of retinoblastoma protein (pRB) expression in esophageal squamous cell carcinoma.

BACKGROUND AND OBJECTIVES: The goal was to evaluate the clinicopathological significance of retinoblastoma gene product (pRB) expression in esophageal squamous cell carcinoma. METHODS: We investigated abnormal pRB expression in tumors in 191 patients using an immunohistochemical method in conjunction with anti-RB protein antibody. Surgically resected esophageal squamous cell carcinomas were examined by immunohistochemical analysis for altered pRB expression. RESULTS: Decreased pRB nuclear staining indicating loss of RB function occurred in 82 (43%) of the cases studied. The incidence of decreased pRB expression was higher in tumors with invasion to the adventitia (50%) than in tumors without invasion to the adventitia (33%, P = 0.0188). In addition, the incidence of decreased pRB expression was higher in tumors with lymph node metastasis (50%) than in those without (34%, P = 0.0346). The 3-year survival rates of 82 patients who had tumors with decreased pRB expression (30%) was significantly lower than that of 109 patients who had tumors with normal pRB expression (52%, P = 0.0032). However, in the multivariate survival analysis, pRB expression was not an independent prognostic factor for patients with esophageal squamous cell carcinoma. CONCLUSIONS: Abnormal pRB expression appears to be closely associated with tumor development. However, the existence of tumors with hyperphosphorylated RB protein (inactivated form) in pRB-positive tumors, such as those in the present study, should be considered. Thus, discrimination of this hyperphosphorylated form of RB protein from the unphosphorylated RB protein is needed.

Adult↗
PubMed2000

Nuclear profiles of cancer cells reveal the metastatic potential of gastric cancer.

Nuclear profiles have been reported as useful prognostic predictors in various cancers. Data from computerized morphometry are objective and can be quickly derived using conventional microscopic analysis, but image analysis of nuclear features has only rarely been applied to investigations of gastric cancer. The aim of this study was to evaluate the correlation between one of these morphological nuclear features and the clinicopathological parameters in patients with gastric cancer. The morphometric nuclear feature (nuclear area) was analysed in 400 patients with gastric cancer. In each case, 300 cancer nuclei on routine haematoxylin and eosin-stained slides were analysed through the use of a computer-assisted image analysis system which traced the nuclear profiles (magnificationx400) on a computer monitor. The morphometric data were compared with the patients' clinicopathological status and survival rate. The mean nuclear area (NA) of cancer cells from 400 cases of gastric cancer was 47.2 microm(2). The NAs of cancer cells from tumours with microvessel invasion (lymphatic or venous invasion), lymph node metastasis or hepatic metastasis at the time of operation were significantly larger than those of cancer cells from tumours without such invasion or metastases. Cytokeratin (CK) immunostaining was performed on 2577 lymph nodes from 91 patients with advanced gastric cancer (pT3, pN0, pM0, stage II) to detect micrometastases. CK-positive lymph nodes were detected in 350 of 2577 lymph nodes (13. 6%) and in 62 of 91 patients (68.1%). The mean NA of cancer cells from 62 tumours with micrometastases (44 microm(2)) was larger than that of cancer cells from 29 tumours without micrometastases (38.8 microm(2), p=0.043), and a significant positive correlation was detected between the NAs of cancer cells from 91 tumours and the number of micrometastatic lymph nodes of 91 patients (rho=0.278, p=0. 008). Cancer cells with large NA correlated strongly with haematogenous and lymph node recurrence or relapse after gastrectomy and the NA of cancer cells was identified as an independent prognostic factor in gastric cancer. Nuclear morphometry is an objective, reproducible, and technically uncomplicated procedure. The NA of cancer cells correlates closely with the metastatic potential of gastric cancer. Nuclear morphometry may therefore be useful for the selection of patients who are at risk of haematogenous or lymph node metastatic recurrence after surgery.

Adenocarcinoma↗
PubMed2000

Limited operation for patients with T1 esophageal cancer.

BACKGROUND/AIMS: Transhiatal esophagectomy without thoracotomy has been introduced as a minimally invasive operation to prevent postoperative complications in patients with relatively early-stage esophageal cancer who have preoperative pulmonary or cardiovascular complications or who are in a high age bracket. However, this procedure for patients with esophageal cancer remains controversial, especially as regards curative surgery because complete intrathoracic lymphadenectomy cannot be performed in this operation. Thus, cancer recurrence after this operation has been considered to be high. To evaluate the benefits of this less invasive surgery for patients with T1 esophageal cancer, the prognoses of patients who underwent transhiatal esophagectomy without thoracotomy were compared with those of patients who underwent traditional esophagectomy with thoracotomy. METHODS: Between 1989 and 1998, 33 patients with T1 esophageal cancer were operated on in our hospital. We introduced transhiatal esophagectomy without thoracotomy in 19 patients who were over 70 years old or who had preoperative complications (transhiatal group). The remaining 14 patients were treated with the transthoracic procedure (transthoracic group). These 33 patients were followed up at our hospital until the end of 1999. The postoperative complications and prognoses in the two groups were compared. RESULTS: We were able to reduce the operation time using the transhiatal procedure. Even though no significant difference was detected, there were fewer postoperative pulmonary complications with this procedure (11%) than with the transthoracic procedure (21%). The incidences of in-hospital mortality did not differ between the two groups. Cancer recurrence was detected in 5 of 19 patients (26%) in the transhiatal group and in 5 of 14 patients (36%) in the transthoracic group; no difference was observed (P=0.562). The 5-year survival rate (58%) of the transhiatal group was no different from that of the transthoracic group (62%, P=0.69). CONCLUSIONS: Complete intrathoracic lymphadenectomy cannot be performed along with transhiatal esophagectomy; however, the prognoses of patients who were treated with this procedure were no different from those of patients who were treated with transthoracic esophagectomy. Thus, transhiatal esophagectomy without thoracotomy might be a justifiable operation for compromised patients with T1 esophageal cancer.

Aged↗
PubMed2000

Combined analysis of p53 and retinoblastoma protein expressions in esophageal cancer.

BACKGROUND: p53 gene mutation and abnormal p53 protein expression, also loss of the retinoblastoma gene and protein expression are frequently associated with esophageal squamous cell carcinoma (ESCC). Recently, the prognostic significance of the combined analysis of p53 protein and retinoblastoma protein (pRB) has been reported in non-small cell lung cancer. However, in ESCC, the prognostic significance of the combined analysis of these proteins remains unclear. In this study, we immunohistochemically analyzed the p53 protein and pRB expressions in surgically resected ESCC, and we evaluated the prognostic significance of the combination of these proteins. METHODS: We analyzed p53 protein and pRB expressions immunohistochemically in 191 surgically resected ESCC cases. Overexpression of p53 and loss of pRB were considered abnormal. RESULTS: Overexpression of p53 protein was detected in 79 patients (41%) and decreased pRB nuclear staining occurred in 82 (43%). The Kaplan-Meier survival curve showed that absence of pRB expression was significantly associated with shortened survival (p = 0.001), whereas expression of p53 was not significantly associated with survival. Moreover, p53 and pRB status individually were not independent prognostic factors in multivariate survival analysis. With respect to pRB and p53, the tumors could be grouped into four categories: p53-/pRB+ (31%); p53-/pRB- (27%); p53+/pRB+ (26%); and p53+/pRB- (16%). Favorable prognosis was observed in patients with p53-/pRB+ tumors. Multivariate analysis showed p53-/pRB+ status to be an independent prognostic factor. CONCLUSIONS: The combination of p53 protein loss and pRB expression was associated with good prognosis in patients with ESCC.

Adult↗
PubMed2000

Enzymatic synthesis of L-[4-13C]aspartic acid.

An efficient procedure for the production of l-[4-13C]aspartic acid (4-13C-Asp) was investigated. In this procedure, phosphoenolpyruvate carboxylase originating from the methanol-assimilating microbe, Methylobacterium extorquens JCM 2805, was used for the production of labeled oxaloacetic acid from phosphoenolpyruvate (PEP) and NaH13CO3; the oxaloacetic acid was then converted to 4-13C-Asp with glutamic-oxaloacetic transaminase. In this reaction, with starting concentrations of 10 mM PEP, 10 mM NaH13CO3 and 15 mM L-glutamic acid (Glu), the yield was 70%. 4-13C-Asp and Glu in the final reaction mixture were separated by displacement chromatography. The yield of this process was 84%. The overall yield was 59%. The incorporation of 13C at the C-4 position of 4-13C-Asp was confirmed by NMR spectroscopy.

Journal Article↗
PubMed2000

Micrometastasis in lymph nodes and microinvasion of the muscularis propria in primary lesions of submucosal gastric cancer.

BACKGROUND: It is important to clarify the clinicopathologic characteristics of micrometastasis in lymph nodes and microinvasion in primary lesions for the treatment options with regard to submucosal gastric cancer. METHODS: We examined 1945 lymph nodes and 68 primary tumors resected from 79 patients with submucosal gastric cancer. Two consecutive sections were prepared for simultaneous staining with ordinary hematoxylin and eosin and immunostaining with anticytokeratin antibody (CAM 5.2), respectively. RESULTS: The incidence of nodal involvement in 79 patients with submucosal gastric cancer increased from 13% (10/79 patients) by hematoxylin and eosin staining to 34% (27/79 patients) by cytokeratin immunostaining. Micrometastases in the lymph nodes were found in 17 of 69 patients (25%), with cancer-free nodes examined by hematoxylin and eosin. Microinvasion to the muscularis propria was found in 11 of 68 patients (16%) who were histologically diagnosed with submucosal gastric cancer. Survival analysis demonstrated a lesser 5-year survival in the patients with micrometastasis in lymph nodes (82%) and with microinvasion to muscularis propria (73%). A high incidence of nodal involvement was found in submucosal cancers of large size (> 2 cm; 43%), a depressed type (48%), lymphatic invasion (73%), and deeper submucosal invasion (submucosal 3, 53%). A higher incidence of microinvasion was found with the diffuse-type carcinoma (33%). CONCLUSIONS: Cytokeratin immunostaining is useful for detecting micrometastasis and microinvasion in submucosal gastric cancer. Tumor size, macroscopic type, lymphatic invasion, and the depth of submucosal invasion are strongly associated with lymph node involvement.

Adult↗
PubMed2000

Reduced E-cadherin expression and enlargement of cancer nuclei strongly correlate with hematogenic metastasis in colorectal adenocarcinoma.

BACKGROUND: Synchronous and metachronous hematogenic metastases are frequently detected in patients with colorectal carcinoma. Once these metastases have developed, the prognoses of patients are poor. Previously, we reported that enlargement of cancer nuclei significantly correlated with metastatic potential of gastric cancer and hepatocellular carcinoma. Moreover, recently it has been reported that reduced expression of E-cadherin is associated with tumor metastasis. To evaluate the correlation between nuclear area (NA) of cancer cells and expression of E-cadherin, and to elucidate whether these factors correlate with clinical outcome in patients with colorectal carcinoma, 105 consecutive patients were investigated. METHODS: In each case, the NAs of 600 cancer nuclei were analyzed by means of a computer-assisted image analysis system and E-cadherin expression was detected immunohistochemically by an anti-E-cadherin monoclonal antibody. The expression levels of E-cadherin were divided into three groups according to the percentages of E-cadherin-positive cells (level 0: positive cells < or = 50%, level 1: 50% < positive cells < or = 80%, level 2: positive cells > 80%). RESULTS: The mean NA of cancer cells in 105 tumors was 57 microm2. The NAs of cancer cells enlarged in proportion to the decrease of E-cadherin expression levels (level 0, n = 48, 62 microm2; level 1, n = 35, 57 microm2, level 2, n = 22, 46 microm2, P = 0.002). The 10-year survival rates decreased in proportion to the reduced E-cadherin expression levels (80% in level 2, 64% in level 1, and 42% in level 0, P = 0.004). Moreover, the 10-year survival rate of 54 patients with large NA tumors (< or = 54 microm2, 36%) was significantly poorer than that of 51 patients with small NA tumors (< 54 microm2, 80%, P < 0.001). The NA of cancer cells was recognized as an important predictor for prognosis and hematogenic metastasis. Although reduced E-cadherin expression was not recognized as the risk factor for hematogenic metastasis, 80% of patients who developed hematogenic metastasis had tumors with both enlarged cancer nuclei and reduced E-cadherin expression. CONCLUSIONS: Detection of NA of cancer cells and E-cadherin expression in patients with colorectal carcinoma may reveal important information for hematogenic metastasis.

Adenocarcinoma↗
PubMed2000

Multipoint imprinting analysis in sporadic colorectal cancers with and without microsatellite instability.

Disrupted imprinting is implicated in certain tumorigenesis. Since aberrant methylation has been described for a majority of microsatellite instability (MSI)-positive sporadic colorectal cancers, we have investigated alteration to the imprinting in 55 sporadic colorectal cancers with or without MSI. Loss of imprinting (LOI) of IGF2 and PEG1/MEST was observed in 42% and 35% of informative cancers, respectively. H19 expression was not detected in 24% of informative cancers. SNRPN and NDN retained monoallelic expression in all the cancers examined. These findings indicate no simultaneous disruption of the imprinted genes. LOI of IGF2 and PEG1/MEST was also observed in colorectal mucosa from almost all the patients with LOI in tumor tissue. Moreover, MSI-positive colorectal cancers exhibit LOI of IGF2 with a high frequency compared to MSI-negative cancers (P=0.013). These observations, consistent with a previous report, establish an association between LOI of IGF2 and MSI in colorectal cancers and provide insight into susceptibility of tumor development.

Alleles↗
PubMed2000

Mutated p53 in tumors, mutant p53 and p53-specific antibodies in the circulation in patients with gastric cancer.

The accumulation of mutated p53 in tumor cells results in the presence in the circulation of mutant p53 (p53m) and the production of p53-specific antibodies (p53Ab). We examined the relationships among these phenomena and analyzed their clinical implications in 62 patients with gastric cancer at various stages. Expression of p53 in tumors was studied by an immunohistochemical method and circulating p53m and p53Ab were quantitated with commercially available enzyme-linked immunosorbent assay kits. The detectable expression of p53 in tumors and circulating p53Ab was recognized in 28 (45.2%) and 7 (11.3%) of the 62 patients, respectively. The number of patients with higher levels of circulating p53m increased with the progression of the depth of cancer invasion. Patients with any positive findings for the three p53-related parameters had a poorer prognosis, and the difference was statistically significant in patients with p53Ab. When survival was analyzed in terms of the combination of the three p53-related parameters (detectable expression of p53 in tumor cells, high levels of p53m and p53Ab in the circulation), a significantly poorer prognosis was associated with an increase in the number of positive parameters. Analysis of p53 in tumor cells, together with analysis of circulating p53m and p53Ab, could improve the accuracy of prognosis in patients with gastric cancer.

Aged↗
PubMed1999

Computerized nuclear morphometry is a useful technique for evaluating the high metastatic potential of colorectal adenocarcinoma.

BACKGROUND: Nuclear profiles have been reported to be useful prognostic predictors in various cancers. Data from computerized morphometry are objective and are quickly obtained by conventional microscopic analysis. However, this image analysis of nuclear features has been only rarely applied to investigations of colorectal adenocarcinoma. The aim of this study was to evaluate the correlation between the morphologic nuclear features and clinicopathologic parameters in cases of colorectal adenocarcinoma. METHODS: Morphometric nuclear features (nuclear area, perimeter, and shape) were analyzed in 343 patients with colorectal carcinoma and in 57 patients with colorectal adenoma. In each case, 300 nuclei of carcinoma or adenoma cells were analyzed on routine hematoxylin and eosin stained slides by means of a computer-assisted image analysis system that involved tracing the nuclear profiles (magnification x400) on a computer monitor. The morphometric data were compared with patients' survival, clinicopathologic status, and DNA ploidy pattern of tumors. RESULTS: The mean nuclear area (NA) enlarged from normal colorectal mucosa to adenoma and carcinoma (normal mucosa: n = 343, mean NA = 19 micrometer(2); adenoma: n = 57, mean NA = 34 micrometer(2); mucosal carcinoma: n = 15, mean NA = 45 micrometer(2); P < 0.001). In 343 colorectal carcinomas, NAs of cancer cells in tumors with lymphatic invasion, venous invasion, lymph node metastasis, or hepatic metastasis were significantly larger than those of cancer cells in tumors without such factors. The mean NA of DNA aneuploid tumors was larger than that of DNA diploid tumors (P < 0.001). The nuclear area of cancer cells was determined to be one of the independent prognostic factors in multivariate analysis (P < 0.001). Moreover, the large nuclear area of cancer cells was recognized as one of the risk factors of metachronous hematogenic metastasis in patients after curative surgery. CONCLUSIONS: Data from computerized morphometry are objective and can be obtained rapidly by conventional microscopic analysis. The nuclear area of cancer cells appears to predict 1) the ability of cancer cells to invade the microvessels in the colorectal wall and 2) the ability of cancer cells to metastasize to the lymph nodes or liver. Therefore, nuclear morphometry is beneficial in mass screening to select patients who are at risk of hematogenic or lymph node metastatic recurrence after curative surgery for colorectal carcinoma.

Adenocarcinoma↗