Biomedical subjects

N Kaibara

Publications and source records attributed to N Kaibara.

At least 55 records · Page 3Linked to original sources

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

[Interim report on JFMTC Study no. 21 on the effectiveness of UFT as an adjuvant therapy for semi-advanced cancer of the stomach].

This interim report, for findings as of May, 1998, covers data on 435 gastrectomized patients with semi-advanced stomach cancer collected from 144 institutions between November, 1993 and March, 1996. The active arm of the study involved CDDP i.p. administration of 70 mg/m2 at the time of resective surgery, followed by UFT oral administration for one year at 3-4 capsules daily. A randomized control involved no adjuvant therapy after CDDP i.p. administered as in the active arm. The results obtained indicated no significant difference between the groups in terms of 3 year survival or disease free survival rates. Reports appearing elsewhere have suggested that 3-4 capsules/day of UFT may be insufficient to reach the threshold of the effective tissue level, and that 6 capsules may be necessary to obtain the expected results. (JFMTC: Japanese Foundation of Multidisciplinary Treatment for Cancer).

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2000

[Interim report of JFMTC study no. 20 on the effectiveness of high dose CDDP plus 5-FU regimen as an adjuvant therapy for far-advanced cancer of the stomach].

This interim analysis of the JFMTC study as of May, 1998 covers 321 gastrectomized patients with far-advanced stomach cancer from 135 institutions between November, 1993 and March, 1996. The intensive therapy group (I-group) received CDDP i.p. administration on resective surgery with 70 mg/m2 followed by CDDP i.v. of 80 mg/m2 (day 1, i.v.), accompanying 5-FU of 350 mg/m2/day (day 1-5, c.v.i.) in the 4th, 8th and 12th weeks. The I-group was randomly compared with the standard therapy group (S-group) of MMC of 6 mg/m2 i.v. in the 4th, 8th and 12th weeks and UFT of 3-4 capsules daily for postoperative one year. The results obtained were that 1. adverse reactions were found more in the I-group than in the S-group, particularly notable in the decrease in blood cells, loss of appetite and nausea/vomiting, and incidence of grade 3 or more being 13% (neutrophile leukocytes), 26% and 21%, respectively; 2. there was no significant difference between I- and S-groups in terms of 3-year survival or disease-free survival rates. (JFMTC: Japanese Foundation of Multidisciplinary Treatment for Cancer).

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2000

Expression of thymidylate synthase in relation to survival and chemosensitivity in gastric cancer patients.

Expression of thymidylate synthase (TS) has been studied as a prognostic factor and mechanism of drug resistance in gastric cancers. The relationship between TS expression in surgically resected specimens and clinicopathological factors was examined in 216 gastric cancer patients. Immunohistochemical demonstration of the protein was achieved using an anti-TS polyclonal antibody. Positive TS staining was observed in 50 patients (23.1%). Lymph node metastasis was more frequent in patients with TS-positive tumors than in those with TS-negative tumors (P<0.01). Patients were followed for more than 5 years and survival was examined. In 163 patients who received fluorouracil (FU)-based chemotherapy, the overall 5-year survival rate was 41.8% for patients with TS-positive tumors and 57.0% for patients with TS-negative tumors (P<0.01). In the 53 patients who did not receive chemotherapy, these figures were 25.6% and 79.5%, respectively (P<0.05). In patients with T3 gastric cancer who were treated with curative gastrectomy, however, FU-based chemotherapy did not affect survival of either patients with TS-positive tumors or with TS-negative tumors. Multivariate analysis also revealed TS expression to be a significant variable for predicting postoperative survival (P<0.05). These results indicate that TS expression can be used as an independent prognostic factor for patients with gastric cancer. However, TS expression is not a major predictor of the efficacy of FU-based chemotherapy.

Adult↗

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↗

PubMed1999

The expression of transforming growth factor-beta1 is significantly correlated with the expression of vascular endothelial growth factor and poor prognosis of patients with advanced gastric carcinoma.

BACKGROUND: Transforming growth factors beta (TGFs beta) are involved in a variety of important cellular functions, including cell growth and differentiation, adhesion, migration, extracellular matrix formation, and immune function. Moreover, it has been reported that TGFs beta are correlated with angiogenesis. However, the role of TGF-beta as an angiogenic factor in gastric carcinoma is still unclear. METHODS: TGF-beta1 expression was determined in 101 patients with gastric carcinoma by immunohistochemical procedures, and this expression was compared in the current study with both the expression of vascular endothelial growth factor (VEGF), which is thought to be the most potent angiogenic factor, and microvessel density, to evaluate the effect of TGF-beta1 on the angiogenesis of gastric carcinoma tissues. RESULTS: TGF-beta1 expression was detected in 23 tumors (22.8%). TGF-beta1 expression was more frequent in differentiated than in undifferentiated gastric carcinoma. Furthermore, TGF-beta1 expression was significantly correlated with the depth of invasion and the stage of disease. There was a close correlation between TGF-beta1 expression and VEGF expression. There was no correlation between TGF-beta1 expression and microvessel density, whereas VEGF expression was significantly correlated with microvessel density. With regard to prognosis, the 5-year survival rate was 55.9% for patients with TGF-beta1 positive tumors and 67.0% in patients with TGF-beta1 negative tumors. Accordingly, the prognosis for patients with TGF-beta1 negative tumors was significantly better than that for patients with TGF-beta1 positive tumors. Multivariate analysis indicated that lymph node metastasis, tumor size, and TGF-beta1 expression were independent prognostic factors. CONCLUSIONS: These results suggest that TGF-beta1 might be associated with tumor progression by indirectly stimulating angiogenesis through the up-regulation of VEGF expression in gastric carcinoma.

Adenocarcinoma↗

PubMed1999

Clinical significance of spontaneous apoptosis in advanced gastric adenocarcinoma.

BACKGROUND: Spontaneous apoptosis has been detected in gastric carcinoma. However, the clinicopathological significance of this remains unclear. The objective of this study was to investigate the correlation between spontaneous apoptosis and the clinicopathologic and biologic characteristics of advanced gastric carcinoma. In addition, the prognostic significance of spontaneous apoptosis of tumors was evaluated. METHODS: The occurrence of apoptotic cell death (apoptotic index [AI]) in 97 patients with advanced gastric carcinoma was analyzed by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick end labeling method. The Ki-67 labeling index (LI), expression of p53 and p21, DNA ploidy pattern, microvessel density (MVD), density of dendritic cells (DCs) in tumors, and degree of lymphocytic infiltration (LI) of the tumors were compared with the AI for each patient. In addition, the prognostic significance of AI was evaluated in these patients. RESULTS: The mean AI of the 97 tumors was 2.05% (range, 0-11.31%). Statistical analyses revealed significant correlations between the AIs and the Ki-67 LIs (P = 0.0004) and between the AIs and the density of DCs (P = 0.0007), as well as an inverse correlation between the AIs and the intratumoral MVD (P = 0.0064). In addition, the AI of 47 tumors with high grade LI (2.94+/-2.51%) was significantly higher than that of 50 tumors with low grade LI (1.22+/-0.93%) (P<0.0001). However, the authors failed to find a significant correlation between the AIs and expression of p53 and p21 and the DNA ploidy pattern. In 93 surviving patients, the 5-year survival rate of 45 patients who had tumors with high AIs (> or =1.47; 82%) was significantly better than that of 48 patients who had tumors with low AIs (<1.47; 60%) (P = 0.0264). CONCLUSIONS: The findings of the current study suggest that the tumors with low neovascularization and high local immunoreactivity may regulate their progression by apoptosis. Moreover, less extensive apoptosis in gastric adenocarcinoma may contribute to disease progression and could be correlated with a poorer prognosis.

Adenocarcinoma↗

PubMed1999

S-phase accumulation precedes apoptosis induced by preoperative treatment with 5-fluorouracil in human colorectal carcinoma cells.

BACKGROUND: In this study, the authors examined the correlations among enhancement of apoptosis, changes in cell cycle distribution, and expression of Ki-67 in human colorectal carcinoma cells during different durations of preoperative treatment with 5-fluorouracil (5-FU). METHODS: Forty-one patients with advanced colorectal carcinoma were divided into 4 groups, which received intravenous 5-FU at 500 mg/body/day preoperatively for 3 days (n = 11), 5 days (n = 13), 7 days (n = 9), or 10 days (n = 8). Patients were further divided into two subgroups according to the DNA ploidy pattern of their tumors, i.e., diploid or aneuploid. Apoptotic cells were stained by the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) method. The expression of Ki-67 was examined by immunohistochemical staining. Flow cytometry was used to analyze changes in cell cycle distribution. RESULTS: Apoptosis of cancer cells was mostly increased in the 7-day group (apoptotic index [Al]: 18.3+/-1.7%] compared with that of the 3-day, 5-day (AI: 11.3+/-2.3% and 13.2+/-2.8%, respectively) (P < 0.01), or 10-day (Al: 16.2+/-2.1%) (P < 0.05) groups. The expression of Ki-67 was reduced with increasing prolongation of 5-FU administration, from 55.2+/-2.1% in the 3-day group to 38.1+/-2.7% in the 10-day group. The authors also assessed the S-phase fraction (SPF) of cancer cells to evaluate changes in cell cycle distribution caused by 5-FU. All tumor samples from patients treated by 5-FU showed S-phase accumulation. The ratio of SPF (after 5-FU/before 5-FU) was higher in the 5-day group (2.35+/-0.78) than in the 3-day (1.71+/-0.48), 7-day (1.68+/-0.55), or 10-day (1.20+/-0.20) groups (P < 0.05). DNA ploidy pattern of the tumor had no influence on the enhancement of apoptosis, the increased ratio of SPF, or the decrease in proliferative activity of colorectal carcinoma cells induced by 5-FU. CONCLUSIONS: S-phase accumulation preceded apoptotic cell death when intravenous 5-FU was administered continuously to human colorectal carcinoma cells.

Apoptosis↗

PubMed1999

The expression of vascular endothelial growth factor and proliferative activity of cancer cells in gastric cancer.

BACKGROUND/AIMS: Vascular endothelial growth factor (VEGF) is one of the most important factors for angiogenesis in various malignant tumors. However, the clinicopathological and biological significance of the expression of VEGF in gastric cancer remains unclear. In this study, we investigated the relationship between the expression of VEGF and the clinicopathological and biological status of advanced gastric cancer, all of the same stage. PATIENTS/METHODS: The expression of VEGF was immunohistochemically examined using the polyclonal antibody A-20 in tumors from 97 patients with invasion of the serosa but no lymph-node metastasis (t3, n0, stage II). The results were compared with clinicopathological and biological status (microvessel density and proliferative activity) of tumors. RESULTS: Expression of VEGF was detected in 27 of 97 tumors (28%). The mean microvessel density (MVD) of 27 VEGF-positive tumors (458/mm2) was higher than that of 70 VEGF-negative tumors (331/mm2, P=0.0001). However, the proliferative activity expressed as the Ki-67 labeling index (LI; percentage of immunostained cancer cells) of 27 VEGF-positive tumors (13.8%) was significantly lower than that of 70 VEGF-negative tumors (26.7%, P=0.0002). In 48 tumors with low proliferative activity of cancer cells (Ki-67 LI < or =18%), 20 (42%) tumors expressed VEGF, and these tumors had a high MVD (4461/mm2). In the 93 surviving patients, the 5-year survival rate of the 25 patients with VEGF-positive tumors (64%) was not different from that of the 68 patients with VEGF-negative tumors (73%, P=0.4296). CONCLUSION: Advanced gastric carcinoma with low proliferative activity may produce VEGF and may have high angiogenic potential in order for the tumor itself to grow. However, the prognosis of patients with such tumors was not unfavorable.

Adult↗

PubMed1999

Detection of telomerase activity in esophageal squamous cell carcinoma and normal esophageal epithelium.

BACKGROUND/AIMS: Relatively little has been reported about the telomerase activity of esophageal squamous cell carcinoma or normal esophageal epithelium. In this study, we have evaluated whether telomerase activity is a useful marker for detecting malignancies in the esophagus. PATIENTS/METHODS: Esophageal carcinomas and normal esophageal tissues adjacent to carcinomas were obtained from 52 surgically treated, unselected patients, and normal esophageal epithelium from 11 non-cancerous patients were obtained by means of biopsy. The telomeric repeat amplification protocol (TRAP) assay was used for detection of telomerase activity in these samples. The incidence of detection of telomerase activity in esophageal carcinoma was compared with that of telomerase activity in normal esophageal epithelium. Moreover, the clinicopathological characteristics of telomerase-positive tumors were compared with those of telomerase-negative tumors. RESULTS: Of the 52 carcinomas, 40 (77%) had detectable telomerase activity. However, telomerase activity was detected in 45 of 52 (87%) normal tissue samples adjacent to carcinomas and in 8 of 11 (73%) normal esophageal epithelium from non-cancerous patients. In esophageal cancer, no significant difference was detected in the clinicopathological findings between the telomerase-positive and -negative cases. CONCLUSION: These results indicate that not only esophageal squamous cell carcinomas but also normal esophageal epithelium show strong telomerase activity. Thus, telomerase activity may not be a good marker for the detection of carcinoma in the esophagus.

Aged↗

PubMed1999

The expression of thymidine phosphorylase correlates with angiogenesis and the efficacy of chemotherapy using fluorouracil derivatives in advanced gastric carcinoma.

The expression of thymidine phosphorylase (TP) and the density of microvessel in advanced gastric carcinoma were examined by immunohistochemistry to evaluate the significance of TP. The expression of TP was negative in 72 cases, positive in 54. The microvessel density correlated with the expression of TP. In total cases, patients with TP-positive tumours survived longer than those with TP-negative tumours. In patients treated with fluorouracil derivatives (FUs), the expression of TP significantly correlated with favourable prognosis and with unfavourable prognosis in those not treated with FUs. The patients with TP-positive tumours, the prognosis of patients treated with FUs was significantly better than that of those not treated with FUs. In patients with TP-positive tumours, treatment with FUs and lymph node metastasis were independent prognostic factors according to the Cox proportional hazards model. Depth of invasion and lymph node metastasis were independent prognostic factors in patients with TP-negative tumours. The determination of the expression of TP might be useful for predicting the efficacy of post-operative chemotherapy using FUs to prevent recurrence in advanced gastric carcinoma patients who undergo curative gastrectomy.

Adenocarcinoma↗

PubMed1999

Computerized nuclear morphometry: a new morphologic assessment for advanced gastric adenocarcinoma.

OBJECTIVE: To evaluate the correlation between the morphologic nuclear features and clinicopathologic parameters in patients with advanced gastric cancer. SUMMARY BACKGROUND DATA: Nuclear profiles have been reported as useful prognostic predictors in various cancers. Data from computerized morphometries are objective and quickly derived using conventional microscopic analysis. However, this image analysis of nuclear features has rarely been applied to investigations of gastric adenocarcinoma. Moreover, it remains to be shown what types of biologic factors influence the nuclear features. METHODS: Morphometric nuclear features (nuclear area, perimeter, and shape) were analyzed in 202 patients with serosal-invaded gastric cancer (stage II and III) who underwent curative gastrectomy. In each case, 300 cancer nuclei were analyzed on routine hematoxylin and eosin-stained slides through the use of a computer-assisted image analysis system by tracing the nuclear profiles (magnification x400) on a computer monitor. The morphometric data were compared with patient survival, clinicopathologic status, DNA ploidy pattern of tumors, expression of p53 protein, and proliferative activity of cancer cells. RESULTS: Lymph node metastasis, lymphatic invasion, and venous invasion were more frequently detected in patients with large nuclear areas. Significant correlations were detected between the size of the nuclear area of cancer cells and the biologic factors of tumors, such as expression of p53, Ki-67 labeling index, and DNA ploidy pattern. The 5-year survival rate of the 100 patients in the large-nuclear group (nuclear area >45.3 microm2) was 47.6% and was significantly lower than the 74.4% rate of the 98 patients in the small-nuclear group (nuclear area < or =45.3 microm2). Moreover, the nuclear area was found to be an independent prognostic factor in the multivariate analysis. CONCLUSIONS: Gastric cancer cells with a large nuclear area express mutated p53 protein and have high proliferative activity. Moreover, such cancer cells have high potential for invasion to the microvessels in the gastric wall. Thus, nuclear morphometry is a new and useful morphologic predictor for metastatic potential in advanced gastric cancer.

Adenocarcinoma↗

PubMed1999

Clinical significance of the detection of thymidine phosphorylase activity in esophageal squamous cell carcinomas.

In this study, we obtained fresh samples of tissue (tumors, adjacent normal mucosas, and metastatic lymph nodes) from 64 patients (metastatic lymph nodes were obtained from 16 patients) with esophageal cancer who underwent esophagectomy between 1993 and 1998. The thymidine phosphorylase (dThdPase) levels of tumors as determined by the ELISA method were compared with clinicopathological findings of tumors and were evaluated for their usefulness as a prognostic parameter for these patients. The dThdPase levels of tumors (221 +/- 21 U/mg protein) and metastatic lymph nodes (253 +/- 51 U/mg protein) were significantly higher than the dThdPase level of normal mucosas (53 +/- 7 U/mg protein, p < 0. 001). The dThdPase levels of tumors did not correlate with the histopathological grading of tumors, the depth of tumor invasion, and lymph node metastasis. The 3-year survival rate of 32 patients with a high level of dThdPase (42%) was not different from that of 32 patients with a low level of dThdPase (52%, p = 0.267). Moreover, the dThdPase level of tumors was not an independent prognostic factor for patients with esophageal cancer. These findings suggest that the level of dThdPase activity in esophageal cancers may not correlate with tumor progression and may not be a useful prognostic marker for patients with esophageal squamous cell carcinoma.

Aged↗

PubMed1999

Detection of loss of heterozygosityat microsatellite loci in esophageal squamous-cell carcinoma.

Microsatellite alterations at 3 genetic loci (chromosomes 2p, 3p and 17p) were analyzed in 25 tumors (20 primary tumors and 5 metastatic lymph nodes) from 20 patients after surgical treatment for esophageal cancer. DNA samples from tumors were compared with control DNA from lymphocytes obtained from the peripheral blood of the individual patients. Microsatellite alterations [microsatellite instability (MSI) and loss of heterozygosity (LOH)] were detected in 15% of 20 primary tumors with marker D2S123 (chromosome 2p), 55% with marker D3S1067 (chromosome 3p) and 50% with marker TP53 (chromosome 17p). The 3-year disease-free survival rate of the 10 patients who had tumors without alterations or with an alteration at only 1 of 3 microsatellite loci was 75% and it was better than that of the 10 patients who had tumors with alterations at 2 or 3 microsatellite loci (48%, p = 0.049). This finding suggests that esophageal cancer with alterations at multiple microsatellite loci might have strong malignant potential. However, MSI was only detected in one of 20 patients, which suggests that MSI might not play an important role in the development of this cancer. Three of 5 metastatic lymph nodes showed no LOH even though primary tumors of these patients exhibited LOH with 1 or 2 markers, and 1 metastatic lymph node had LOH that was detected with D3S1067 even though the primary tumor of this patient had no LOH with all markers. Thus, clonal heterogeneity might exist in esophageal squamous-cell carcinomas.

Aged↗

PubMed1999

Soluble CD44 variant 6 as a prognostic indicator in patients with colorectal cancer.

The expression of CD44v6 is well known as a useful marker of tumor progression and prognosis in colorectal cancer. In this study, we evaluated the serum levels of soluble CD44 splice variants containing exon v6 (sCD44v6) and examined the histological expression of CD44v6 in patients with colorectal cancer. Serum samples were obtained from 44 primary colorectal cancer patients before surgery. We used enzyme-linked immunosorbent assay to determine the serum levels of sCD44v6. The expression of CD44v6 was examined by immunohistochemical staining of the primary tumors obtained from the same patients. Both the serum concentration of sCD44v6 and the expression of CD44v6 were significantly associated with lymph node metastasis (p < 0.05). Furthermore, the serum level of sCD44v6 was higher in those patients with CD44v6-positive tumor tissues (154.4 +/- 34.8 ng/ml) than in those with CD44v6-negative ones (130.7 +/- 32.3 ng/ml; p < 0.05). The 5-year survival rate was significantly lower in patients with high serum levels of sCD44v6 (52.4%) than in those with low levels of sCD44v6 (78.0%; p < 0.05), and it was also significantly lower in patients with CD44v6-positive cancer (42.1%) than in those with CD44v6-negative cancer (84%; p < 0. 01). We concluded that preoperative elevation in the serum levels of sCD44v6 might be a prognostic indicator for patients with colorectal cancer.

Adenocarcinoma↗

PubMed1999

Serum level of a soluble receptor for interleukin-2 as a prognostic factor in patients with gastric cancer.

Increased levels of a soluble receptor for interleukin-2 (sIL-2R) have been found in the serum from patients with a variety of malignancies. Levels of sIL-2R have not previously been examined in a large group of patients with gastric cancer as a possible indicator of prognosis. Serum levels of sIL-2R were measured preoperatively by an enzyme-linked immunosorbent assay in 121 patients with gastric cancer. The preoperative levels of sIL-2R in patients with gastric cancer were significantly higher than those in normal controls. An elevated level of sIL-2R was significantly correlated with certain clinicopathologic features, which included depth of invasion, lymph node metastasis, lymphatic vessel invasion, blood vessel invasion and clinical stage. The postoperative survival time of patients with elevated levels of sIL-2R was significantly shorter than that of patients with normal levels. Furthermore, a multivariate analysis using Cox's proportional hazards model showed that the combination of levels of carcinoembryonic antigen and sIL-2R was an independent indicator of prognosis. Thus, the serum level of sIL-2R might be a useful prognostic indicator in patients with gastric cancer.

Adenocarcinoma↗

PubMed1999

Administration in a hypotonic solution is preferable to dose escalation in intraperitoneal cisplatin chemotherapy for peritoneal carcinomatosis in rats.

An animal model of intraperitoneal (i.p.) cisplatin chemotherapy using hypotonic solutions of sodium chloride has been developed as a treatment for peritoneal carcinomatosis. The concentrations of platinum in the plasma and in the i.p. fluid of Donryu rats were measured after i.p. injection of hypotonic (103 or 154 mosm/l) and isotonic (308 mosm/l) solutions that contained an equal amount of cisplatin. The maximum concentration (Cmax) and the area under the curve of concentration versus time (AUC) of platinum in the plasma increased proportionately with increases in the dose of cisplatin and they were significantly higher in rats given cisplatin in hypotonic solutions than in those given the drug in isotonic solution. The Cmax and AUC of total platinum were similar for the solution of 103 mosm/l with 2.5 mg/kg cisplatin and the isotonic solution with 5.0 mg/kg cisplatin. The Cmax and AUC of free platinum in the plasma did not increase with increases in the dose of cisplatin in isotonic solution but did increase after hypotonic injection. However, the solutions of lower osmolarity gave a decreased AUC of platinum in the i.p. fluid. Hypotonic conditions continued for 30 min at most after i.p. injection of hypotonic solutions. When the same dose of cisplatin was given to rats with tumors derived from AH100B carcinoma cells, the amount of platinum taken by i.p. solid tumors from the solution of 103 mosm/l was about twice that from the isotonic solution and was much the same as that taken up from the isotonic solution with twice the amount of cisplatin. These results indicate that hypotonic i.p. cisplatin chemotherapy might be preferable to escalation of the dose of i.p. cisplatin in the treatment of peritoneal carcinomatosis.

Animals↗