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Biomedical subjects

T Kakizoe

Publications and source records attributed to T Kakizoe.

At least 19 recordsLinked to original sources

Tumorigenicity and gene amplification potentials of cyclin D1-overexpressing NIH3T3 cells.

Cyclin D1 is a key regulator of the G1-S transition in cell cycle, and its gene is amplified and overexpressed in many cancers. To address the gene amplification potential of the cells in which the cyclin D1 gene expression is deregulated, we have established NIH3T3 clones with various levels of cyclin D1 transgene message. Those transfectants showed anchorage independent growth and tumorigenicity without in vitro morphological transformation. The degree of the transformed phenotype apparently correlated with the cyclin D1 expression level. Upon selection by N-(phosphonoacetyl)-L-aspartate (PALA), the cyclin D1-transfected NIH3T3 cells showed a higher ability to develop PALA-resistant colonies by amplifying the CAD gene, as compared to the parental NIH3T3 cells.

3T3 Cells

Rapid isolation of cell-type-specific protein tyrosine kinases by degenerate polymerase chain reaction combined with differential hybridization technique.

To identify protein tyrosine kinase (PTK) genes preferentially expressed in renal cell carcinoma cell line, we screened a PTK-cDNA-enriched library constructed from RNA of an renal cell carcinoma cell line with a PTK probe, each produced from renal cell carcinoma, gastric cancer or esophageal cancer cell lines by degenerate polymerase chain reaction. Two cDNA fragments of PTK genes, FRK and FLT-3, were isolated from the PTK-cDNA-enriched library of the renal cell carcinoma cell line by differential hybridization technique. The FRK cDNA clone represented 15.8% of the PTK-cDNA-enriched library from the renal cell carcinoma cell line, while the FLT-3 cDNA clone was 2.8% of the same library. Both of the two PTK genes were expressed preferentially in renal cell carcinoma cell lines. This method, described here, is useful for the rapid isolation of PTK cDNA fragments, including a low abundant cDNA, preferentially expressed in a specific cell line.

Base Sequence

Bacillus Calmette-Guérin treatment of existing papillary bladder cancer and carcinoma in situ of the bladder. Four-year results. The Bladder Cancer BCG Study Group.

BACKGROUND: Intravesical instillation therapy of Bacillus Calmette-Guérin (BCG) has become a standard treatment for carcinoma in situ (CIS) of the urinary bladder. However, there have been few reports concerning the direct effect of BCG on existing tumors classified as Ta or T1. In the first stage of this clinical study, 157 patients were treated with BCG intravesical instillation (Tokyo 172 strain [BCG Co. Ltd., Tokyo, Japan]; 80 mg weekly for eight times) by our Study Group. The efficacy on existing tumors was a complete response (CR) rate of 84.4% and 66.4% and a partial response (PR) of 6.3% and 20.8% for 32 cases of CIS and 125 cases of Ta or T1 tumors, respectively. METHODS: In the second stage of this study, the authors investigated the outcome of the 138 patients who had achieved CR or PR in the first stage. One hundred twenty (87.0%) of the patients were followed fully. Of those patients, 52 were randomized to receive prophylactic (maintenance) therapy consisting of BCG of 40 mg monthly for 12 times (Group A), whereas 55 were randomized to an untreated control group (Group B). Thirteen other patients refused to be randomized and were followed without prophylactic instillation. RESULTS: The median follow-up period was 48 months for Group A and 42 months for Group B. In Groups A and B, the beneficial effect of the BCG therapeutic instillation persisted for a long time, and the 3-year nonrecurrence rate was 77.6% in Group A and 74.2% in Group B. Disease progression was observed rarely. CONCLUSION: For patients in whom transurethral resection of tumors of the bladder (TUR-Bt) alone is unlikely to eliminate the tumor, intravesical BCG is potentially the treatment of choice.

Administration, Intravesical

Intraductal tumor involvement and renal parenchymal invasion of transitional cell carcinoma in the renal pelvis.

Surgical specimens obtained from 21 patients with renal pelvic cancer, in which the tumor was located on the side of the renal parenchyma, were reviewed with special reference to tumor involvement with renal collecting ducts and/or renal parenchyma. Four distinct entities were found: 1) 4 tumors that involved the collecting ducts without invasion of renal parenchyma, 2) 4 tumors that involved the collecting ducts with microscopic invasion of renal parenchyma, 3) 5 tumors that invaded the renal parenchyma by less than 5 mm. and were microscopically identified as being without ductal involvement and 4) 6 tumors that exhibited extensive renal parenchymal invasion. The patients with intraductal tumors had good prognosis as did those with microscopic invasion except for 1 who died of lymph nodes metastases. Conversely, 6 patients with extensive invasion had a poor prognosis, 5 (88%) of whom died of recurrent tumor or distant metastases. The differences in these 4 entities may be important, especially if large numbers of patients are examined, and they may ultimately be shown to have a different prognosis.

Adult

Basic fibroblast growth factor as a candidate tumor marker for renal cell carcinoma.

The present investigation was conducted to determine serum levels of basic fibroblast growth factor (FGF) by enzyme immunoassay in patients with various urogenital tumors. Renal cell carcinoma had a higher tendency (28 of 52, 53.8%) toward increased serum levels of basic FGF than any of the other urogenital tumors, and increased serum basic FGF was detected more frequently in patients with advanced renal cell carcinoma. Analysis of histological pattern indicated that renal cell carcinoma with a solid or tubular component is more likely to produce basic FGF. However, no significant difference was seen between the percentage of clear cell type tumor patients with increased serum basic FGF (50.0%) and the percentage of granular cell type tumor patients with increased serum basic FGF (66.7%). Five of 8 patients with renal cell carcinoma who underwent selective renal venous sampling before nephrectomy showed increased serum basic FGF in the renal vein from the affected kidney. After resection of the affected kidney to remove the cancer, serum basic FGF disappeared within 2 weeks. However, residual huge tumor or postoperative disease prolonged the increased levels of basic FGF in 2 patients, indicating that basic FGF is produced from and secreted by tumor tissue itself. These findings suggest that serum basic FGF can be useful in the diagnosis, and in evaluating the prognosis, of patients with renal cell carcinoma.

Biomarkers, Tumor

[Prognosis after radical surgery in prostatic cancer patients with lymph nodes metastases].

We investigated prognosis of clinically localized prostatic adenocarcinoma patients who revealed to have had lymph nodes metastases by undergoing radical surgery. Eighty six patients were operated during the last 15 years under the clinical diagnosis of A2, 9 patients, B1, 15 B2, 13 and C, 49, respectively. Total prostatectomy was done to 51, total cystoprostatectomy to 33 and total pelvic excentration to 2 patients. Of these patients, 22.2% with stage A2, 20.2% with B1, 7.7% with B2 and 43.8% with C had positive nodes and the rate of positive nodes in stage C was significantly higher than that in other stages (p < 0.01). Regarding histological differentiation, 15.4% of well, 23.7% of moderate and 51.6% of poor by differentiated had positive nodes and the rate of positive nodes in poor by differentiated was significantly higher (p < 0.01). In 2 of 21 cases whose lymph nodes were dissected to the level of the aortic bifurcation, positive nodes were detected only in the external and common iliac areas. These two cases were missed, i.e., "false negative" if limited nodes dissection was performed. All patients with positive nodes were treated with hormonal therapy. The 5-year cancer specific survival rate of patients with positive (n = 27) and negative (n = 59) nodes were 66.4% and 92.4%, respectively. The prognosis of patients with positive nodes were significantly worse than that of patients with negative nodes (p < 0.001). Among 27 patients with positive nodes, significant prognostic factor was not number or extent of positive nodes, but histological differentiation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma

Endoscopic findings and clinical manifestation of gastric anisakiasis.

OBJECTIVES: To identify the endoscopic findings and clinical manifestations of anisakiasis, we studied 87 cases of gastric anisakiasis. METHODS: Patient information was analyzed by means of patient records. The interval between the day of intake of Anisakis and endoscopic examination was determined in 86 cases. Then the endoscopic findings of each interval were elucidated. RESULTS: Moderate to severe gastric mucosal edema tends to occur within 1 or 2 days after Anisakis infection, accompanied by leukocytosis. As to the sites of penetration of Anisakis, 55% of cases were found in the greater curvature with severe mucosal edema. Among 87 cases, four patients experienced anisakiasis twice during the interval examined, and six patients had past histories of anisakiasis before the investigated interval. CONCLUSIONS: Gastric anisakiasis may be caused by an allergic reaction to the Anisakis antigen. There is a classic relationship between clinical and endoscopic findings and the interval after Anisakis administration. Anisakis usually is found in the greater curvature.

Adolescent

Solitary renal melanoma? A case with long survival after initial treatment.

A case of a solitary melanocytic renal tumor with no apparent primary lesion or metastasis is reported. Pathologically the tumor was composed of cells with brown pigmentation that strongly reacted to monoclonal antibody HMB-45 immunohistochemically. Few mitotic figures, mild nuclear atypia and nucleolar prominence were observed. These findings confirmed that the tumor cells were melanogenetic but the malignant potential of the tumor was low in comparison to that of typical malignant melanoma. The patient is doing well 44 months after partial resection of the renal tumor and postoperative chemotherapy. The interesting pathological feature may account for the unique clinical course.

Female

Promotional effect of two-generation exposure to a high-fat diet on prostate carcinogenesis in ACI/Seg rats.

Epidemiological studies have shown an association between a high-fat diet and a high mortality rate from breast, colon, and prostate cancer. However, the promotional effect of a high-fat diet on experimental carcinogenesis has not been fully established for the prostate. In this study, the effect on prostatic carcinogenesis of two-generation exposure to a high-fat diet was investigated using ACI/Seg rats, a strain with high incidence of spontaneous prostate cancer. A high-fat diet (20% corn oil) or a low-fat diet (5% corn oil) was given to mother rats during pregnancy and the newborn male rats were fed the same diets for 60 or 100 weeks after weaning. At 100 weeks, atypical hyperplasia and adenocarcinoma of the prostate were respectively found in 73.3% (11/15) and 20.0% (3/15) of the high-fat diet group and in 20.0% (3/15) and 0% (0/15) of the low-fat diet group. There was a significant increase of atypical hyperplasia in the high-fat diet group (P < 0.05). The serum concentrations of sex hormones and the prostatic proliferative activity as measured by flow cytometry or bromodeoxyuridine labeling were not significantly affected by diet. These results showed that feeding a high-fat diet before conception and from the beginning of organogenesis had a marked promotional effect on the early stage of prostate carcinogenesis in rats.

Animals

Markedly increased amounts of messenger RNAs for vascular endothelial growth factor and placenta growth factor in renal cell carcinoma associated with angiogenesis.

The presence of mRNAs for vascular endothelial growth factor (VEGF) and a VEGF-related protein, placenta growth factor (PIGF) was examined in 29 cases of renal cell carcinoma tissues and adjacent normal kidney tissues and in 4 human renal cell carcinoma cell lines. Northern blot analysis showed that 26 of 27 hypervascular renal cell carcinoma tissues (96%) exhibited a markedly elevated level (3-13 fold) of VEGF mRNA compared to the adjacent normal kidney tissues. Even tumors of small size, whenever they were hypervascular, overexpressed VEGF mRNA. We also demonstrated that mRNA for PIGF was expressed in 21 of 23 hypervascular renal cell carcinoma tissues (91%) but was not detected in the adjacent normal kidney tissues. Two hypovascular carcinoma tissues neither overexpressed VEGF mRNA nor had PIGF mRNA. VEGF mRNA was detected in four human renal cell carcinoma cell lines, while PIGF mRNA was not. There was no difference in the level of basic fibroblast growth factor mRNA between tumor tissues and normal kidney tissue, although our previous study demonstrated elevated basic fibroblast growth factor protein in the serum of renal cell carcinoma patients (K. Fujimoto et al., Biochem. Biophys. Res. Commun., 180: 386-392, 1991). Taken together, these results suggest that VEGF, PIGF, and basic fibroblast growth factor are cooperatively working to increase the angiogenesis in renal cell carcinoma in vivo.

Angiogenesis Inducing Agents

Urethral involvement in female bladder cancer patients: mapping of 47 consecutive cysto-urethrectomy specimens.

We reviewed 47 consecutive step-sectioned cysto-urethrectomy specimens of bladder cancer in female patients to determine the incidence and characteristics of urethral involvement. Of the 47 cases 43 were transitional cell carcinoma: 10 (23%) papillary, 9 (21%) papillo-nodular and 18 (42%) nodular cancer, and 6 (14%) primary or secondary carcinoma in situ. There were 23 cases (54%) of invasive carcinoma of more than stage pT1 and 27 (63%) were grade 3 lesions. Urethral cancer was observed in only 3 cases: 1 stage pT4, grade 3 papillo-nodular cancer developed widely in the bladder and, overriding the bladder neck and proximal urethra, stage pTa, grade 2 papillary cancer was detected, while in 2 with nodular invasive lesions of the bladder (including the bladder neck) urethral cancer was detected either as a direct invasive extension via urethral carcinoma in situ or as an intralymphatic spread without urethral mucosal change. These findings indicate the necessity for prophylactic urethrectomy in cases of papillary or papillo-nodular cancer encroaching on the bladder neck, and nodular invasive cancer infiltrating the bladder neck and trigone. In other cases, preservation of the urethra seems possible for bladder reconstruction in female bladder cancer patients to ensure normal voiding after cystectomy.

Adenocarcinoma

Percutaneous transhepatic portacaval shunt for high-risk esophageal varices.

Percutaneous transhepatic portacaval shunt (PTPS) was performed in a patient with high-risk esophageal varices prior to sclerotherapy. PTPS was accomplished with the aid of two catheters. The first catheter was placed in the right hepatic vein under ultrasonographic guidance, and the second was placed in the portal vein. The two catheters were then connected together. The color of the esophageal varices changed from blue to white, and serum protein levels were increased 8 weeks after PTPS. Sclerotherapy was then performed without any difficulty. PTPS is the easy and quick method of performing a portacaval shunt and may have importance for the management of patients with high-risk esophageal varices prior to the treatment of sclerotherapy or liver transplantation.

Aged

[Prevention of cancer recurrence by infusion of activated autologous lymphocytes].

Activated and expanded autologous peripheral blood lymphocytes by cultivation with immobilized anti-CD3 antibody and IL-2 have been infused to the patients with hepatocellular carcinoma after culative operation as a randomized clinical trial. This study is on-going and primary efficacy endpoints of this study were disease-free survival and overall survival, and the sample size for the study was designed as a minimum of 146 patients. From interim analysis at the second year from start of the study, Eligible cases were 101, 49 cases in treated group and 52 cases in control. Recurrences were confirmed 13 cases from treated group and 22 cases from control group. Minor adverse reaction were observed in 28 cases (57%).

Antibodies, Monoclonal

[Surgical treatment for renal cell carcinoma].

Metastatic or locally advanced renal cell carcinoma is refractory to chemotherapy and radiotherapy. Surgical treatment is the mainstay of treatment in these cases. The concept of surgical treatment of renal cell carcinoma was discussed by classifying the procedures into four categories: 1) radical nephrectomy; 2) nephron sparing surgery, such as partial nephrectomy and enucleation for small renal cancer detected incidentally by ultrasonography and CT; 3) extended surgery for cases having IVC tumor thrombus or with invasion of neighboring organs; and 4) surgery for metastatic disease. New therapies such as LAK, alpha-Interferon and IL-2 do not improve the 20% response rate. Gene therapy using appropriate vectors for introduction of IL-2. Interferon or GM-CSF genes to renal cancer cells is still at an experimental stage.

Carcinoma, Renal Cell

A prospective randomized trial for treating stages B2 and C prostate cancer: radical surgery or irradiation with neoadjuvant endocrine therapy.

A randomized clinical trial of neoadjuvant endocrine therapy followed by either surgery or irradiation and a resumption of endocrine therapy for stages B2 and C prostate cancer has been in progress since 1989. A hundred patients entered the trial between 1989 and 1993, and 95 cases were evaluated. Forty-six patients received surgery and 49 were treated with irradiation. Neoadjuvant endocrine therapy for two months resulted in prostate shrinkage and prostate specific antigen lowering. Except for two patients, one dying of a progression of disease and the other of another concurrent cancer, all are alive with an average follow-up term of 25 (range 3-53) months. The good prognostic results obtained from both treatment groups at present seem to be due in part to the neoadjuvant endocrine therapy; but in order to reach a final conclusion further comparisons need to be made.

Aged