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T Kakizoe

Publications and source records attributed to T Kakizoe.

At least 37 records · Page 2Linked to original sources
PubMed2000

Asian studies of cancer chemoprevention: latest clinical results.

Chemoprevention trials in Asia, including those already completed and those now ongoing, are reviewed. Information was mainly collected from Japan, Korea and China. Each country features its own characteristics. Cancer chemoprevention trials targeting, from various aspects, hepatocellular carcinoma, gastric cancer and colon cancer have been, and are now being, conducted in Japan. Japan also has a long history of basic carcinogenesis research and carcinogenic research using animal experiments. In Korea, ginseng is the main focus of studies of chemopreventive agents. A large body of information has been collected and prospective studies are also ongoing. In China, the Linxian study, a cooperative study participated in by China and the NCI of the USA, is well known and the results impressive. However, we must exercise caution because, for example, the population of Linxian are chronically deficient in multiple vitamins and trace minerals. This situation may, therefore, differ from that observed in other countries. In any event, chemoprevention studies will be popular from an economical point of view even in Asia because cancer is becoming the number one cause of death in these countries.

China↗
PubMed2000

Prevention and treatment of urothelial premalignant and malignant lesions.

Bladder cancer is believed to develop through reversible premalignant stages followed by irreversible steps, and ending in invasive cancer giving rise to distant metastases. Because of the variation in the clinical course it has also been suggested that different forms of cancer develop along different molecular pathways leading to tumor presentations of various malignant potential. Today we treat and prognosticate bladder cancer on the basis of clinical and histologic findings that are insufficient to assess all the biologic potential of these tumors. Understanding the pathogenesis of bladder cancer might lead to a more precise identification of particular tumors with regard to clinical aggressiveness, resulting in individualized strategies for treatment and prophylaxis. Bladder cancer is seldom diagnosed in its preclinical stage, it is instead detected at cystoscopy and virtually never recognized as an incidental finding on autopsy. Therefore its "natural history" largely reflects that of "treated" disease. The true incidence of premalignant and malignant epithelial changes is not known. Incidences of hyperplasia and dysplasia of approximately 10% and approximately 5%, respectively and only occasional findings of cancer itself were reported in two autopsy series. Urothelial dysplasia is generally believed to be premalignant and a putative precursor of invasive cancer but unfortunately there has been a lack of standardization in terms of terminology and diagnosis. There is also a need for an agreed definition of the boundary between premalignancy, i.e. urothelial changes that have some but not all the features of carcinoma in situ, and malignancy, especially when considering potentially harmful treatments to prevent this transition. Most new diagnostic tools available and being tested today compare new detection techniques with traditional methods such as cytology or conventional histology of malignant rather than premalignant changes. There is probably also a short preclinical latency, as implied by the incidental findings of bladder cancer at autopsy, which makes it necessary to define how and when to promote early detection and treatment. Future studies therefore have to concentrate on methods for early detection of disease as well as characterization of host susceptibility, evaluation of exposure to carcinogens and potential effects of preventive measures. It is also likely that the improved tools of molecular prognostication will allow us to design trials more precisely in order to tailor therapeutic strategies.

Animals↗
PubMed2000

Six-year disease-free survival of a patient with metastatic eyelid squamous cell carcinoma and colon adenocarcinoma after repeated postoperative adoptive immunotherapy.

A 74-year-old male was affected concurrently with squamous cell carcinoma of the left eyelid and adenocarcinoma of the colon, both with lymph node metastasis. He underwent exenteration of the left orbit with left modified radical neck dissection and subsequently resection of the transverse colon with regional lymph node dissection. The patient has been treated by an adoptive immunotherapy as a sole postoperative modality without receiving any chemotherapeutic agents causing immunosuppression. For the adoptive immunotherapy, autologous peripheral blood lymphocytes were activated with an immobilized anti-CD3 antibody and IL-2 for 14 days (the CD3-AT cells). The infusion with 1.38 x 10(10) CD3-AT cells has been repeated 150 times in total at the time of writing. Neither recurrence nor additional metastasis has been detected for 6 years after surgery.

Adenocarcinoma↗
PubMed2000

Effects of three-month oral supplementation of beta-carotene and vitamin C on serum concentrations of carotenoids and vitamins in middle-aged subjects: a pilot study for a randomized controlled trial to prevent gastric cancer in high-risk Japanese population.

Prior to a randomized controlled trial to prevent gastric cancer by oral supplementation of beta-carotene and vitamin C in a high-risk Japanese population, we examined the serum response to three-month oral supplementation of beta-carotene (0, 3, 30 mg / day) and vitamin C (0, 50, 1000 mg / day) by a three-by-three factorial design using 54 subjects (age range = 40 - 69 years). Serum concentrations of carotenoids, alpha-tocopherol, and ascorbic acid were examined at baseline, and one, two, and three-month points. Both serum beta-carotene and ascorbic acid were significantly higher in high-dose groups than in each placebo group during the supplementation. The serum beta-carotene increased gradually (597 - 830% increase) during the study, whereas the serum ascorbic acid reached nearly a steady-state at the one-month point and remained stable thereafter (88 - 95% increase). No statistically significant interaction between beta-carotene and vitamin C supplementations was observed either for serum beta-carotene or for serum ascorbic acid. Among carotenoids and alpha-tocopherol examined, serum lycopene in the high-dose beta-carotene group was significantly higher than in the placebo group at all points. No unfavorable change in carotenoids and alpha-tocopherol was observed in any group.

Administration, Oral↗
PubMed2000

Expression of CD44 variants and prognosis in oesophageal squamous cell carcinoma.

BACKGROUND: The CD44 variant (CD44v) isoforms have been noted as markers for tumour metastasis and prognosis in several adenocarcinomas. AIMS: To investigate whether CD44v, especially the CD44v2 (v2) isoform, may be a useful prognostic factor for patients with oesophageal squamous cell carcinoma, using a recently developed monoclonal antibody against a v2 epitope. PATIENTS: 233 patients (211 men and 22 women; mean age 61.9 years), with oesophageal squamous cell carcinomas curatively removed without additional treatment between 1987 and 1996 at the National Cancer Center Hospital, were analysed for CD44v expression. METHODS: The expression of CD44v was evaluated immunohistochemically using monoclonal antibodies against epitopes of the standard and variant protein, in paraffin embedded oesophageal squamous cell carcinoma tissue from 233 patients who had undergone cervical, mediastinal, and abdominal lymphadenectomy (three field dissection) for oesophagectomy. The data were evaluated for any correlation with clinicopathological indices or prognosis. RESULTS: Although total CD44 and CD44v6 (v6) were respectively observed in 99% and 97% of the cancer specimens, the expression of v2 was only 30%. Patients whose tumours were v2 positive had a significantly better prognosis than those whose tumours were v2 negative (p = 0.031). Furthermore, in patients without lymph node metastasis, v2 positivity alone was a significant independent factor of prognosis (relative risk of death associated with v2 negativity, 4.7; p = 0.037) in multivariate analysis. CONCLUSIONS: These results indicate that v2 is a useful marker for clinical prognosis in patients with oesophageal squamous cell carcinoma. Particularly in patients without lymph node metastasis, v2 status may thus have implications for the use of adjuvant chemotherapy and/or radiotherapy in patients with oesophageal cancer at an early stage.

Adult↗
PubMed2000

Inverse association of soy product intake with serum androgen and estrogen concentrations in Japanese men.

The cross-sectional relationships of soy product intake and serum testosterone, estrone, estradiol, sex hormone-binding globulin, and dihydrotestosterone were examined in 69 Japanese men. Soy product intake was estimated from a semiquantitative food frequency questionnaire. Serum estradiol concentration was significantly inversely correlated with soy product intake (r = -0.32, p = 0.009), and serum estrone concentration was nonsignificantly inversely correlated with soy product intake (r = -0.24, p = 0.05) after controlling for age, body mass index, smoking status, and ethanol intake. Total and free testosterone concentrations were inversely correlated with soy product intake after controlling for the covariates, but these correlations were of border line significance (r = -0.25, p = 0.05 and r = -0.25, p = 0.06, respectively). Similar correlations were observed for these hormones with isoflavone intake from soy products. The data suggest that soy product intake may be associated with the endogenous hormone levels in Japanese men.

Aged↗
PubMed1999

DNA methylation analysis using bisulfite treatment and PCR-single-strand conformation polymorphism in colorectal cancer showing microsatellite instability.

The combination of bisulfite treatment and PCR-single-strand DNA conformation polymorphism (SSCP) analysis is proposed for quantitative methylation assay. We applied this procedure to the methylation analysis of the hMLH1 promoter region in colorectal cancer. An analysis of mixtures of known amounts of methylated and unmethylated DNA revealed a linear relation. Using a calibration curve, proportions of methylated DNA were calculated. The hMLH1 promoter region was highly methylated in about 80% of microsatellite instability (MSI) (+) colorectal cancers, but in none of the MSI(-) colorectal cancers. A significant correlation existed between hypermethylation of the hMLH1 promoter and MSI, as in previous reports. In conclusion, bisulfite-PCR-SSCP (BiPS) analysis could be applied to the rapid identification of methylation status in multiple samples, quantification of methylation differences, and detection of methylation heterogeneity in amplified DNA fragments.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Identification of receptor genes in renal cell carcinoma associated with angiogenesis by differential hybridization technique.

To screen the receptor genes in renal cell carcinoma (RCC) associated with angiogenesis, we performed differential hybridization of the cDNA library of membrane-type protein tyrosine kinases (mPTKs). Three thousand plaques of a mPTKs-enriched cDNA library were screened with mPTKs mixture probes produced from hypervascular RCC tissues and RCC cell lines. Six different cDNA fragments of the PTK genes were isolated, and the sequence analysis showed that these represented cDNAs for TIE1, KDR, FMS, FGFR-4, JAK1 and HCK. Of these genes, the expression of TIE1, KDR, and FGFR-4 was studied in RCC tissue and cell lines by Northern blot analysis. We also investigated the expression of vascular endothelial growth factor (VEGF), placenta growth factor (PlGF) and their receptor FLT-1. In all the hypervascular RCC tissues, the amounts of mRNAs for KDR and FLT-1 were increased compared to adjacent normal tissues. The TIE1 and FGFR-4 genes were also overexpressed in most of the hypervascular RCC tissues, while no mRNA of KDR, FLT-1, or TIE1 could be detected in any of the four human RCC cell lines. The amounts of the VEGF and PlGF mRNAs were increased in hypervascular RCC tissues, while VEGF mRNA was detected in the four cell lines but PlGF mRNA was not. FGFR-4 mRNA was expressed in three of the four cell lines. These results suggest that KDR, FLT-1, PlGF and TIE1 mRNAs are present in the mesenchymal cells of RCC, while VEGF and FGFR-4 genes are expressed in RCC cells themselves in vivo.

Blotting, Northern↗
PubMed1999

CD95 ligand expression enhances growth of murine renal cell carcinoma in vivo.

The CD95/CD95 ligand (CD95L) system plays an important role in the induction of lymphoid apoptosis and has been implicated in the suppression of immune responses. In this system, two murine CD95L-transfected renca clones and a control renca clone transfected only with the vector were implanted into the subcapsule of the left kidney of Balb/c and Balb/c nude mice. Both CD95L-expressing and control renca clones formed macroscopic tumors in all of the Balb/c and Balb/c nude hosts 14 days after implantation. Growth of tumors of murine CD95L-transfected renca cells was significantly better than that of control renca cells in Balb/c mice, while the growth advantage of CD95L transfectants was not observed in Balb/c nude mice. Lymphocytes underwent apoptosis mainly in the periphery of the CD95L-expressing tumors but not in control tumors grown in Balb/c mice, while lymphocytes undergoing apoptosis were not observed in CD95L-expressing tumors or in control tumors grown in Balb/c nude mice. Neutrophilic recruitment was rarely observed in CD95L-expressing or control tumors. CD95L expressed on renca cells possibly suppressed immune responses against renca tumors by inducing apoptosis of the infiltrating lymphocytes. However, CD95L-expressing renca cells did not form tumors in the renal subcapsule of allogeneic C3H/HeJ mice.

Animals↗
PubMed1999

Urinary incontinence after non-nerve-sparing radical prostatectomy with neoadjuvant androgen deprivation.

OBJECTIVES: The impact of non-nerve-sparing retropubic radical prostatectomy (RRP) for prostate cancer combined with neoadjuvant androgen deprivation on urinary control is not well documented. We examined the incidence and severity of urinary incontinence after such therapy and determined the etiologic factors causing this complication. METHODS: We examined the postoperative continence status of 104 consecutive patients admitted to the National Cancer Center Hospital who underwent RRP with wide resection of the pelvic nerves after neoadjuvant androgen deprivation. Incontinence was scored according to the number of pads used daily by the patient for urinary leakage. The severity of incontinence was analyzed according to patient age, weight of resected specimen, status of cancer stage, duration of neoadjuvant androgen blockade therapy, preoperative length of membranous urethra, and duration of urethral catheterization after surgery. We also measured the configuration and diameter of the reconstructed bladder neck by retrograde cystourethrography. RESULTS: In 104 patients examined, the percentage of patients who became dry postoperatively was 22% at 1 month, 47% at 3 months, 69% at 6 months, and 78% at 1 year. Of 81 patients who became dry postoperatively at any interval, 22 (27%) became continent within 1 month of RRP, 49 (61 %) were continent within 3 months, 71 (88%) became continent by 6 months, and another 10 (12%) became continent between 6 and 12 months postoperatively. Of 48 patients who were followed up for more than 1 year and for whom continence status at 1 month after surgery was available, all patients who used 1 to 2 pads per day (13 of 13) at 1 month after surgery regained continence by 1 year after surgery. However, only 62% of patients (16 of 26) who required more than 3 pads per day at 1 month after surgery became dry by 1 year after surgery. Only age (older than 70 years) and large prostate size (weight of surgical specimen more than 40 g) temporarily influenced the recovery of urinary continence after surgery. Dilation of the bladder neck evaluated by retrograde cystourethrography was prominent in severely incontinent patients in the immediate postoperative period. CONCLUSIONS: Our experience in patients who undergo non-nerve-sparing RRP after neoadjuvant androgen deprivation closely matches published surveys of patient-reported complications. Postoperative incontinence is not a major contraindication for non-nerve-sparing RRP after neoadjuvant endocrine therapy. Dilation of the bladder neck affected the recovery from incontinence, highlighting the importance of adequate reconstruction of the bladder neck.

Aged↗
PubMed1999

Long-term results of a randomized trial for the treatment of Stages B2 and C prostate cancer: radical prostatectomy versus external beam radiation therapy with a common endocrine therapy in both modalities.

OBJECTIVES: To improve the treatment of locally advanced prostate cancer (Stages B2 and C), a prospective randomized trial was conducted to compare radical prostatectomy versus external beam radiotherapy with the combination of endocrine therapy in both modalities. METHODS: One hundred patients were enrolled and 95 were evaluated. Forty-six patients underwent radical prostatectomy with pelvic lymph node dissection, and 49 were treated with radiation by linear accelerator with 40 to 50 Gy to the whole pelvis and a 20-Gy boost to the prostatic area. For all patients, endocrine therapy was initiated 8 weeks before surgery or radiation, and continued thereafter. The living patients were asked to respond to a quality-of-life questionnaire. RESULTS: The follow-up period ranged from 6.0 to 94.4 months (median 58.5). The progression-free and cause-specific survival rates at 5 years were 90.5% and 96.6% in the surgery group and 81.2% and 84.6% in the radiation group, respectively. The surgery group had better progression-free and cause-specific survival rates (P = 0.044 and 0.024, respectively). More patients in the surgery group complained of urinary incontinence. The questionnaire revealed that quality of life was less disturbed in the radiation group. CONCLUSIONS: Radical prostatectomy combined with endocrine therapy may contribute to the survival benefit of patients with locally advanced prostate cancer. External beam radiotherapy in combination with endocrine therapy can be used in selected patients because of its low morbidity.

Adenocarcinoma↗
PubMed1999

Effect of Bcl-2 overexpression in human prostate cancer cells in vitro and in vivo.

BACKGROUND: Cancer cells often develop mechanisms to resist apoptosis and the extent of such anti-apoptotic ability has been shown to parallel tumor progression in various malignancies. Among various molecules implicated in regulating apoptosis pathway, bcl-2 and its family members are best characterized. METHODS: To investigate the effect of bcl-2-mediated anti-apoptotic ability on tumor growth and progression in prostate cancer, a cell line overexpressing bcl-2 (LNCaP/bcl-2) was established by genetically engineering a prostate cancer cell line LNCaP. Tumor growth of LNCaP/bcl-2 was compared with the parental cell line in vitro and in vivo. RESULTS: LNCaP/bcl-2 cells show resistance to apoptosis caused by nutrient deprivation and did not arrest when cultured in serum-free or androgen-free medium, while parental LNCaP cells or LNCaP cells transfected with the vector only (LNCaP/control) underwent extensive apoptosis on nutrient deprivation and sustained growth suppression in serum-free or androgen-free medium. When injected subcutaneously into nude mice, tumors deriving from LNCaP/bcl-2 cells grew faster compared with LNCaP/control for about 3 weeks (P = 0.02), but this effect was not evident after 5 weeks. Upon castration, the control tumors regressed but LNCaP/bcl-2-derived tumors showed resistance, as was previously reported. CONCLUSIONS: These data confirm the notion that anti-apoptotic function of bcl-2 is oncogenic and confers resistance to androgen deprivation and also indicate that it may also play a critical role in earlier stages of tumorigenesis.

Androgens↗
PubMed1999

Alveolar architecture of clear cell renal carcinomas (< or = 5.0 cm) show high attenuation on dynamic CT scanning.

BACKGROUND: To establish the correlation between tumor appearance on CT and tumor histology in renal cell carcinomas. METHODS: The density and attenuation patterns of 96 renal cell carcinomas, each < or = 5 cm in greatest diameter, were studied by non-enhanced CT and early and late after bolus injection of contrast medium using dynamic CT. The density and attenuation patterns and pathological maps of each tumor were individually correlated. RESULTS: High attenuated areas were present in 72 of the 96 tumors on early enhanced dynamic CT scanning. All 72 high attenuated areas were of the clear cell renal cell carcinoma and had alveolar architecture. The remaining 24 tumors that did not demonstrate high attenuated foci on early enhanced scanning included three clear cell, nine granular cell, six papillary, five chromophobe and one collecting duct type. With respect to tumor architecture, all clear cell tumors of alveolar architecture demonstrated high attenuation on early enhanced scanning. CONCLUSION: Clear cell renal cell carcinomas of alveolar architecture show high attenuation on early enhanced dynamic CT scanning. A larger number of patients are indispensable to obtaining clear results. However, these findings seem to be an important clue to the diagnosis of renal cell carcinomas as having an alveolar structure.

Carcinoma, Renal Cell↗
PubMed1999

Reduction of the side effects of an antitumor agent, KRN5500, by incorporation of the drug into polymeric micelles.

For intravenous (i.v.) injection of a water-insoluble antitumor drug, KRN5500, we have successfully incorporated KRN5500 into polymeric micelles. In the present study, in vitro and in vivo anti-tumor activity against several human tumor cell lines and toxicity in mice of polymeric micelles incorporating KRN5500 (KRN/m) were evaluated in comparison with those of the prototype KRN5500. KRN/m was found to express similar antitumor activity to KRN5500 in the in vitro and in vivo systems. However, the vascular damage and liver focal necrosis observed with KRN5500 i.v. injection were not seen when KRN/m was administered i.v. Therefore, we expect that KRN/m will be superior to KRN5500 for clinical use and that the methodology of polymeric micelle drug carrier systems can be applied to other water-insoluble drugs.

Animals↗