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Biomedical subjects

T Kakizoe

Publications and source records attributed to T Kakizoe.

At least 55 records · Page 3Linked to original sources
PubMed1999

Diagnosis of pancreatic cancer by detecting telomerase activity in pancreatic juice: comparison with K-ras mutations.

OBJECTIVE: Telomerase activity is reported to be specific and very frequent in human malignancy. K-ras mutations are also very frequently detected in pancreatic cancer, but their specificity for pancreatic cancer is controversial. We examined the telomerase activity and K-ras mutations in pancreatic juice from patients with pancreatic disease. METHODS: Pancreatic juice was obtained endoscopically at endoscopic retrograde pancreatography from 10 patients with pancreatic cancer, three with chronic pancreatitis, and three with a normal pancreas. The telomerase activity in pancreatic juice was assayed by telomeric repeat amplification protocol. K-ras mutations in exon 1 codon 12 were examined by the two-step polymerase chain reaction combined with restriction enzyme digestion, followed by single-strand conformation polymorphism analysis and direct sequencing. RESULTS: Telomerase activity of >5.0 was detected in eight of 10 (80%) subjects with pancreatic cancer, but in none with chronic pancreatitis or normal pancreas. K-ras mutations were detected not only in eight of 10 (80%) subjects with pancreatic cancer but also in two of three with chronic pancreatitis and in one of three with a normal pancreas. CONCLUSIONS: It was shown that the detection of telomerase activity in pancreatic juice is a more useful diagnostic tool for pancreatic cancer than that of K-ras mutations.

Aged↗
PubMed1999

Biological role of HGF/MET pathway in renal cell carcinoma.

PURPOSE: Several lines of evidence show that hepatocyte growth factor (HGF) and its receptor MET play a significant role in the progression of various cancers including renal cell carcinoma (RCC). Our objectives were to evaluate the gene expression of HGF and MET in RCC, and to examine the effect of HGF on the biological activities of cultured RCC cells. MATERIALS AND METHODS: We examined the gene expression of HGF and MET in 27 primary RCC tumors by quantitative competitive RT-PCR. The effects of HGF on in vitro chemoinvasion assay and the expression of matrix metalloproteinase-9 (MMP-9), and the induction of Fas-induced apoptosis were studied by transfection of HGF cDNA to cultured RCC cells, Caki-1. RESULTS: HGF mRNA and MET mRNA were detected in all surgical specimens. The level of expressed HGF mRNA was proportional with the volume of tumor (r = 0.50, p = 0.015). Caki-1 cells overexpressing HGF cells showed enhanced in vitro invasiveness in the chemoinvasion assay and increased activity of 92 kDa type IV collagenase (MMP-9). The sensitivity to Fas-induced cell death was reduced in HGF transfectants, which was reversed by the presence of anti-HGF antibody. CONCLUSIONS: HGF enhanced the invasive properties of cultured RCC cells and inhibited Fas-induced apoptosis in vitro. Both HGF and MET mRNA were expressed in RCC tissues tested. Our results indicate that HGF/MET pathway may have a significant role in the progression of RCC.

Apoptosis↗
PubMed1999

Reduction of integrin beta4 and enhanced migration on laminin in association with intraepithelial spreading of urinary bladder carcinomas.

PURPOSE: The aim of the present study was to investigate the biological and molecular basis of intraepithelial spreading (IES) of carcinomas in situ (CIS) of the urinary bladder, which were considered to be precursors of nodular invasive carcinomas. MATERIALS AND METHODS: The propensity for IES of human transitional carcinoma cells was examined by inoculation into murine renal pelvis and urinary bladder, and the biological character of the cells with a high propensity for IES was explored in vitro. RESULTS: Three of 6 cell lines exhibited a high propensity for IES. When cultured on laminin, these IES cells scattered, whereas 3 non-IES cells and 2 immortalized transitional epithelial cells did not. IES cells showed strong adhesiveness, haptotaxis and enhanced migration on laminin compared with both non-IES and immortalized transitional epithelial cells. In IES cells, expression of the integrin beta4 subunit was markedly reduced and the integrin alpha6beta1 complex was predominant compared with the integrin alpha6beta4 complex. Transfection of IES cells with integrin beta4 subunit cDNA inhibited their ability to migrate on laminin and their propensity for IES. In addition, expression of the integrin beta4 subunit was reduced in surgically resected specimens of CIS of the urinary bladder. CONCLUSION: The results indicate that a reduction in integrin beta4 plays a role in IES of CIS of the urinary bladder through enhanced migration on laminin.

Antigens, CD↗
PubMed1998

Incorporation of water-insoluble anticancer drug into polymeric micelles and control of their particle size.

A water-insoluble anticancer drug, KRN 5500 (KRN), was incorporated into polymeric micelles forming from poly(ethylene glycol-poly(amino acid) block copolymers by physical entrapment utilizing hydrophobic interactions between this drug and the poly(amino acid) chain block of the block copolymers. Three block copolymers were examined for this incorporation; poly(ethylene glycol)-poly(beta-benzyl l-aspartate) (PEG-PBLA) and its two derivatives obtained by partial hydrolysis at the beta-benzyl l-aspartate (BLA) units (PEG-P(Asp, BLA)) and by partial cetyl ester substitution at the BLA units (PEG-P(C16, BLA)), respectively. Among these block copolymers, considerable effects of the cetyl esterification were seen on KRN yield and particle size. Considerable differences in the KRN incorporation yield and particle size were also observed between DMF and DMS used as solvent to dissolve KRN and the block copolymers. Sonication was turned out to be an effective method to obtain a polymer micelles fraction in high efficiency, and sonication was considered to work for separating intermicellar associates into dispersed micelles. A KRN incorporation procedure by dialysis using PEG-P(C16, BLA) and DMSO (as solvent) followed by sonication brought about polymeric micelles of 71 nm in weight-average diameter. This shows successful incorporation of a water-insoluble drug into polymeric micelles by optimizing block copolymer structure and incorporation conditions.

Antibiotics, Antineoplastic↗
PubMed1998

Allelic loss on chromosome 9 in bladder cancer tissues and urine samples detected by blunt-end single-strand DNA conformation polymorphism.

Allelic loss on chromosome 9 is the most frequent and earliest genetic event in bladder carcinogenesis, and its detection in urine samples would be useful for detecting bladder cancer. A highly sensitive method to detect loss of heterozygosity (LOH) at 5 polymorphic loci on chromosome 9p and 9q was developed by the use of blunt-end single-strand DNA conformation polymorphism (blunt-end SSCP) analysis. Tumor tissues, urine samples and peripheral blood lymphocytes from 34 patients with transitional cell carcinoma of the bladder were analyzed. LOHs on 9p and/or 9q were found in 24 (71%) of 34 tumor samples and 23 (70%) of 33 urine samples, while no allelic loss was detected in 20 urine samples from benign urothelial diseases. The frequency of allelic loss in tumor tissues was 67%, 71% and 80% in the pTa, pT1 and > or = pT2 stages and 50%, 80% and 79% in G1, G2 and G3 tumors, respectively. In comparison with a urine cytological examination, LOH on chromosome 9 was detected in 70% of urine samples diagnosed as transitional cell carcinoma, 67% of those as atypia and 70% of those as no malignant cells. Thus, detection of LOH on chromosome 9 from urine samples by blunt-end SSCP is a more sensitive diagnostic modality than cytologic examination for detecting bladder cancer. It would be useful for postoperative management of bladder cancer, particularly when the allelic loss is revealed in the tumor tissues obtained at first surgery.

Carcinoma, Transitional Cell↗
PubMed1998

Inhibition of azoxymethane initiated colon tumor and aberrant crypt foci development by bovine lactoferrin administration in F344 rats.

The influence of bovine lactoferrin (bLf) on colon carcinogenesis was investigated in male F344 rats treated with azoxymethane (AOM). In experiment I, 2% and 0.2% bLf, and Bifidobacterium longum (B. longum) as a positive control at 3% were given in the diet for 4 weeks, along with two s.c. 15 mg/kg injections of AOM on days 1 and 8. The numbers of aberrant crypt foci (ACF) were decreased by both treatments. Similar results were obtained in experiment II of 13 weeks duration. In experiment III, animals were given three weekly injections of AOM and then received 2 or 0.2% bLf, 2% bLf-hydrolysate, or 0.1% bovine lactoferricin (bLfcin) for 36 weeks. No effects indicative of toxicity were noted, but significant reduction in both the incidence and number of adenocarcinomas of the large intestine was observed with almost all the treatments. Thus, the incidences of colon adenocarcinomas in the groups receiving 2 or 0.2% bLf, 2% bLf-hydrolysate, or 0.1% bLfcin were 15%, 25%, 26.3% and only 10%, respectively, in contrast to the 57.5% control value (p < 0.01). ACF values also exhibited reduced development. Investigation of beta-glucuronidase revealed decrease in the cecal contents of animals receiving bLf. In addition, demonstration of enhancement of NK activity by bLf indicated that its inhibitory effects could have been related to elevated immune cytotoxicity.

Animals↗
PubMed1998

Abnormal expression of CD44 variants in the exfoliated cells in the feces of patients with colorectal cancer.

BACKGROUND & AIMS: Recent investigations have shown that CD44 variant exons are frequently overexpressed in human colorectal adenocarcinoma. The aim of this study was to investigate abnormal expression of the CD44 gene in exfoliated cells from patients with colorectal cancer. METHODS: Exfoliated cells in feces from 25 patients with colorectal cancer before and after surgery and from 15 healthy volunteers were analyzed. CD44 standard, variant 6, and variant 10 messenger RNA (mRNA) expressions were examined in the exfoliated cells in feces by using reverse-transcription polymerase chain reaction followed by Southern hybridization with exon-specific probes. RESULTS: CD44 standard mRNA was detected in all samples before and after surgery and in all healthy volunteers. CD44 variant 6 and variant 10 mRNA were detected in 17 of 25 patients (68%) and 15 of 25 patients (60%), respectively, in individual feces obtained before surgery. CD44 variant 6 mRNA and variant 10 mRNA were detected in postoperative samples in 3 of 25 patients (12%) and 7 of 25 patients (28%), respectively. Fifteen of 17 patients who were positive for CD44v6 based on preoperative fecal samples became negative after surgery (88.2%). Similarly, 12 of 15 patients who were CD44v10 positive in preoperative fecal samples were negative postoperatively (80%). CONCLUSIONS: These results suggest that analysis of CD44 variant expression in the exfoliated cells in feces can provide a noninvasive diagnostic test for colorectal cancer.

Adult↗
PubMed1998

Elevated serum interleukin-6 levels in patients with pancreatic cancer.

The vast majority of pancreatic cancer patients have advanced disease at the time of diagnosis and they eventually become so emaciated that death primarily occurs from cancer cachexia. Cancer cachexia may be mediated by certain cytokines such as interleukin-6. In this study, we measured serum interleukin-6 levels in 55 patients with histologically proven pancreatic cancer and investigated their relationships to the clinical status of pancreatic cancer. A control population of 20 normal healthy adults and 25 chronic pancreatitis patients with comparable gender and age distribution characteristics was also studied. Serum interleukin-6 levels were measured using a quantitative sandwich enzyme-linked immunosorbent assay. Thirty pancreatic cancer patients (54.5%) had detectable levels, although interleukin-6 levels were detectable in only one healthy control and in two chronic pancreatitis patients. The specificity of serum interleukin-6 in this population was 93.3%, resulting in high diagnostic accuracy (72.0%). Among the pancreatic cancer patients, the detection rates of serum interleukin-6 levels increased significantly with the disease extent (p < 0.01). Moreover, a significant difference was also found in the detection rates between the 30 pancreatic cancer patients with body weight loss (76.7%) and the remaining 25 patients without weight loss (28.0%, p < 0.01). These results may provide new insight into both diagnosis and treatment of pancreatic cancer, because the diagnostic accuracy of serum interleukin-6 was high and because anti-interleukin-6 therapeutics could improve symptoms in pancreatic cancer patients with high interleukin-6 levels.

Adult↗
PubMed1998

Three cases with familial adenomatous polyposis diagnosed as having malignant lesions in the course of a long-term trial using docosahexanoic acid (DHA)-concentrated fish oil capsules.

The inhibitory effect of n-3 polyunsaturated fatty acids on human colorectal cancer has been speculated on from epidemiological data and animal studies. We conducted a long-term trial of docosahexanoic acid (DHA)-concentrated fish oil capsules for patients in a high-risk group for colorectal cancer. During this trial, we experienced three patients with familial adenomatous polyposis (FAP) diagnosed as having malignant lesions. Three patients with FAP and two patients with multiple (more than 30) colorectal polyps were administered DHA-concentrated fish oil capsules_Hlk427554600[2.2 g of DHA and 0.6 g of eicosapentanoic acid (EPA) per day] for one or two years. Compliance with DHA-concentrated fish oil capsules was more than 90% in four patients and 61% in one patient. A marked increase or decrease in the number of polyps was not observed. Three patients with FAP developed endometrial cancer after 12 months, colon cancer after 24 months and lung cancer after 12 months, respectively. All cancers were diagnosed at an early stage and were resected curatively. We thought that the possibility of developing cancer from the long-term administration of fish oil capsules to patients with FAP needs to be investigated further, and that we should report these cases.

Adenocarcinoma↗
PubMed1998

Transitional cell carcinoma of the urethra in men and women associated with bladder cancer.

Multifocal tumor occurrence in the entire urinary tract in time and space is a well-recognized characteristic of transitional cell carcinoma. Synchronous and asynchronous urethral transitional cell carcinoma, in relation to bladder cancer in male and female patients, is the subject of the present mini-review. It is imperative to rule out male and female patients having a high risk for urethral involvement or urethral recurrence. In male patients, prostatic urethral involvement and stromal invasion mainly due to in situ extension of carcinoma seems to be the most important risk factor. In female patients, bladder neck involvement by cancer seems most important. By excluding male and female bladder cancer patients having these characteristics for simultaneous urethrectomy, other patients are good candidates for reconstruction of the urinary tract after cystectomy by an orthotopic neobladder which will offer a good quality of life to bladder cancer patients.

Carcinoma, Transitional Cell↗
PubMed1998

Point mutations of ornithine decarboxylase gene are an infrequent event in colorectal cancer but a missense mutation was found in a replication error positive patient with hMSH2 germline mutation.

BACKGROUND: Ornithine decarboxylase (ODC; EC 4.1.1.17) is the first rate-limiting enzyme in the biosynthesis of polyamines. ODC protein has a characteristic amino acid sequence, the PEST sequence, which is related to the enzyme's rapid degradation. ODC cDNA prepared from human hepatoma tissues has been reported to show nonsense or missense mutations. METHODS: We examined somatic mutations of ODC cDNA by RT-PCR-SSCP analysis and mRNA expressions by RT-PCR in 50 colorectal cancer tissues to investigate the involvement of ODC gene alterations in colorectal cancers. RESULTS: Increased expression of the ODC gene was observed in 36 cases (86%) out of the 42 examined by RT-PCR. In one case, a missense mutation was found in the cancer tissue but not in normal mucosa. The missense mutation from Asp to Asn at codon 424, in the PEST region, possibly stabilizes the ODC protein. In colorectal cancer, replication error and a germline mutation in hMSH2 gene were observed. CONCLUSIONS: The missense mutation at codon 424 is speculated to be a cause of stabilization and a passenger mutation owing to the mutator phenotype. Since only one of 50 colorectal cancers exhibited a missense mutation of the ODC gene, mutations in ODC gene are not frequent in colorectal cancer. The increased expression of the ODC gene was noted in 86% of colorectal cancer tissues by RT-PCR, however, it was not due to point mutations in ODC coding exons.

Colonic Neoplasms↗
PubMed1998

Increased expression of cyclooxygenase-2 to -1 in human colorectal cancers and adenomas, but not in hyperplastic polyps.

BACKGROUND: Non-steroidal anti-inflammatory drugs can reduce the risk of colorectal cancer. Reportedly, mRNA expression of cyclooxygenase-2 (COX-2) is elevated in human colorectal cancers compared with accompanying normal mucosa. The present study was undertaken to establish a simple analytical procedure to quantify COX-2 expression levels and to characterize COX-2 expression levels in human colorectal cancers, adenomas and hyperplastic polyps. METHODS: The combination of PCR using common primers designed in the highly conserved regions and fluorescence-based single-strand conformation polymorphism (F-SSCP) analysis of the products is used for quantitative determination of the proportions of COX-2 mRNA in human colorectal cancers, adenomas, hyperplastic polyps and accompanying normal mucosa. RESULTS: The present F-SSCP analysis was a simple and powerful method for quantitative determination of the proportions of COX-2 mRNA. The proportion of COX-2 mRNA was higher in cancer tissues than in accompanying normal mucosa in 46 of the 50 cancers. There was no significant correlation between the increase of the COX-2 proportion and tumor location or stages. The enhanced COX-2 expression was also observed in colorectal adenomas. On the other hand, the proportion of COX-2 mRNA in hyperplastic polyps was not significantly different from that in normal mucosa. CONCLUSIONS: The proportion of COX-2 to COX-1 expression was elevated in most human colorectal cancers and adenomas, but not in hyperplastic polyps. Therefore, the increased proportion of COX-2 expression might be an early event in the carcinogenesis of colorectal cancer.

Adenoma↗
PubMed1998

Efficacy of dose-intensified MEC (methotrexate, epirubicin and cisplatin) chemotherapy for advanced urothelial carcinoma: a prospective randomized trial comparing MEC and M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin). Japanese Urothelial Cancer Research Group.

BACKGROUND: To evaluate the antitumor activity in patients with T3b, T4 or metastatic urothelial carcinoma treated with MEC or M-VAC chemotherapy, by performing a multi-center randomized prospective study. METHODS: From 1991 to 1995, 89 patients with T3b, T4 or metastatic urothelial carcinoma were randomly allocated to a methotrexate, epirubicin and cisplatin chemotherapy group (arm 1: S-MEC therapy; n = 29), a dose-intensified MEC therapy combined with G-CSF group (arm 2: I-MEC therapy; n = 30) or a methotrexate, vinblastine, doxorubicin and cisplatin chemotherapy (arm 3: M-VAC therapy; n = 30). At the registration center, the patients were stratified into previously untreated patients and patients with recurrence after radical operation and then randomly allocated to the treatment groups. In each arm, two or more courses of chemotherapy (4-week cycles) were performed. RESULTS: Of the 88 eligible patients, four treated with S-MEC therapy and two treated with I-MEC therapy showed CR. The response rates (CR + PR) were 52% (15/29) with S-MEC therapy, 76% (22/29) with I-MEC therapy and 47% (14/30) with M-VAC therapy. The response rate with I-MEC therapy was significantly higher than that with M-VAC therapy (P = 0.02). Although the incidence of leukopenia was low with I-MEC therapy, the incidence of thrombocytopenia was high with this therapy. CONCLUSION: MEC therapy used in this study is promising in terms of the antitumor effects.

Adult↗
PubMed1998

Pancreatic cancer: medical aspects.

Although pancreatic cancer (PC) continues to be a formidable disease, numerous treatment strategies are evolving that we hope will result in improved patient survival. To prolong the survival of patients with PC, it is essential to detect PC at the earliest stage possible and to develop effective nonsurgical treatments for this disease. The current strategies for the early diagnosis of PC include the development of diagnostic modalities and screening programs for the early detection of PC and the determination of high-risk groups for PC. K-ras mutations in pancreatic juice obtained endoscopically have been studied recently in association with the early diagnosis of PC, although the interpretation of the presence of a mutated K-ras gene requires caution. The role of the current nonsurgical treatments for PC has been limited. Identification of an effective new chemotherapeutic agent is a high priority, and the enrollment of patients with PC with metastatic disease into well-designed clinical trials is essential. New targets for therapy based on the understanding of the molecular biology of PC may provide avenues for future trials. We must continue to search actively for more accurate methods of diagnosis and more effective methods of treatment for PC.

Genes, ras↗
PubMed1998

Expression of CD44 variants and its association with survival in pancreatic cancer.

Since the CD44 variant 6(v6) molecule has been noted as a marker for tumor metastasis and prognosis in several tumors, we examined whether or not v6 is a useful marker for evaluating the prognosis of pancreatic cancer patients. In addition, we attempted to assess the clinicopathological implications for pancreatic cancer of the variant 2 (v2) isoform using a recently developed monoclonal antibody against a v2 epitope. The expression of CD44 variants was evaluated immunohistochemically in paraffin-embedded pancreatic cancer tissues from 42 patients who were confirmed surgically and histologically to have received curative resection. An indirect immunoperoxidase method was used with monoclonal antibodies against epitopes of the standard (CD44s) portion, v6 and v2. Protein expression data were evaluated statistically for any correlations with the length of survival or with histological parameters. The expression of CD44v6 and v2 was observed only in tumor cells, if at all. On the other hand, expression of total CD44 (including CD44v, as well as CD44s) was observed in both tumors and adjacent normal sites. Tumor tissue from 21 (50%) and 16 (38%) patients showed positive immunoreactivity with mAb 2F10 (anti-CD44v6) and mAb M23.6.1 (anti-CD44v2), respectively. The expression of CD44v6 and v2 was correlated with decreased overall survival (P = 0.0160 and P = 0.0125, respectively). A significant correlation was obtained between CD44v2 peptide expression and vessel invasion (P = 0.026). These results suggest that CD44v2 and CD44v6 may be useful markers for poor prognosis in curatively resected primary pancreatic cancer.

Antigens, CD↗