Do the worst histological elements in needle biopsy specimens of prostate cancer predict prognosis?
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Adenocarcinoma↗
Biomedical subjects
M Hosaka
Publications and source records attributed to M Hosaka.
MEK kinase is involved in tumor necrosis factor alpha-induced NF-kappaB activation and degradation of IkappaB-alpha.
Signal-dependent activation of the transcription factor NF-kappaB is dominantly regulated by degradation of IkappaB-alpha protein. However, the signaling pathways that lead to the degradation are not clear. Here we report that mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK) kinase, an activator of stress-activated protein kinases/jun kinase-1 (SAPKs/JNK1), is involved in such signaling pathways. The transient overexpression of MEK kinase in NIH3T3 fibroblasts activates kappaB-CAT reporter expression in a synergistic manner with TNFalpha stimulation. In contrast, overexpression of kinase-negative MEK kinase suppresses TNFalpha-induced reporter expression. The overexpression of MEK kinase suppresses the inhibitory activity of co-transfected IkappaB-alpha on the kappaB-CAT or human immunodeficiency virus-long terminal repeat-luciferase reporter expression and causes the simultaneous disappearance of the overexpressed IkappaB-alpha. The disappearance of exogenous IkappaB-alpha by the overexpression of MEK kinase is prevented by calpain inhibitor-I, an inhibitor of IkappaB-alpha degradation. These results suggest that MEK kinase is a signal mediator involved in TNFalpha-induced NF-kappaB activation and that the activation of NF-kappaB by MEK kinase is regulated through the degradation of IkappaB-alpha.
3T3 Cells↗
Differential effects of overexpression of PKC alpha and PKC delta/epsilon on cellular E2F activity in late G1 phase.
Introduction of a reporter gene containing E2F binding sites linked to the luciferase gene permitted us to detect transient cellular E2F activity in late G1 phase rat 3Y1 fibroblasts. Overexpression of three major protein kinase C (PKC) isozymes expressed in 3Y1 cells caused differing effects on E2F activity depending on the isozymes overexpressed. Overexpression of PKC alpha inhibited E2F activity while the overexpression of PKC delta or PKC epsilon enhanced it, suggesting that these PKC isozymes play different roles in the regulation of E2F activity. Consistent with previous findings that the activation of PKC by TPA in late G1 phase results in the inhibition of DNA synthesis (Huang, C., and Ives, H.E., 1987, Nature 329, 849-850), the addition of TPA in late G1 phase specifically inhibited E2F activity. Overexpression of PKC isozymes resulted in an enhancement of the TPA-induced inhibition of E2F in late G1 phase. This enhancement was observed for all three PKC isozymes examined, suggesting that these PKC isozymes all are potent mediators of the TPA-induced inhibition of E2F activity in late G1 phase.
Animals↗
[Case of renovascular hypertension with pheochromocytoma].
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Adrenal Gland Neoplasms↗
A new method of the electrolyte-free long-term preservation of human sperm at 4 degrees C.
OBJECTIVES: To develop a new method for the long-term preservation of human sperm. SETTING: Andrology laboratory of our hospital. PATIENTS: Thirty-one normal and 19 asthenozoospermic semen samples obtained from patients attending our infertility clinic. The average sperm motility was 70.2% and 36.0% in the normal and asthenozoospermic groups, respectively. INTERVENTIONS: Ejaculated sperm were centrifuged and washed using the electrolyte-free Percoll gradient and then were preserved at 4 degrees C. MAIN OUTCOME MEASURES: The motility of the preserved sperm was analyzed using computer-assisted semen analyzer after the addition of Ham's modified F-10 (GIBCO, Grand Island, NY). RESULTS: In the normal group, motility rate after the addition of Ham's F-10 for 1, 2, and 4 weeks of preservation was 65.4%, 40.4%, and 5.5%, respectively. In the asthenozoospermic group, motility rate after 1 and 2 weeks of preservation was 31.3% and 18.1%, respectively. Preservation solutions containing sodium or potassium decreased motility after preservation. Restoration of preserved sperm was not achieved by incubation alone; however, reinitiation was induced by incubation together with Ham's F-10. CONCLUSIONS: Human sperm in the electrolyte-free solution survived for a long period of time at 4 degrees C and reinitiation of sperm motility after preservation required the addition of Ham's F-10.
Cold Temperature↗
Structure and intracellular localization of mouse ADP-ribosylation factors type 1 to type 6 (ARF1-ARF6).
ADP-ribosylation factors (ARFs) are a family of small GTP-binding proteins that are proposed to be involved in the formation of coated transport vesicles. Although six ARF sequences have been reported in mammals to date, it has been unclear how many ARF members are present in a single organism. In this study, we provide the first direct evidence by cDNA cloning for the presence of all six ARF members in mouse. These proteins are highly conserved across mammalian species and Northern blot analysis revealed that mRNAs for all the members were expressed ubiquitously. Transfection of cells with epitope-tagged ARFs revealed that ARFs 1-3 displayed a perinuclear Golgi localization, while ARFs 4-6 appeared to be widely dispersed throughout the cytoplasm. These results suggest that although all the ARF proteins play fundamental and critical roles in cellular function, they are involved in different vesicular transport processes.
ADP-Ribosylation Factor 1↗
High energy gamma -ray production from Be, C, and Al targets with 65 MeV 3He bombardment.
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Journal Article↗
Molecular genetic diagnosis of von Hippel-Lindau disease: analysis of five Japanese families.
We analyzed deoxyribonucleic acids from blood samples of five Japanese von Hippel-Lindau (VHL) disease families (three familial cases, two new mutations) for the presence of VHL gene mutations by single-strand conformational polymorphism analysis and direct sequencing. Four of the five families showed germ line mutations in VHL gene, comprising 2 missense mutations, 1 deletion, and 1 splice-site mutation. Two families had VHL gene mutations at exon 1; 1 family at exon 3; and 1 family at the splice-site adjacent to exon 3. Presymptomatic patients were accurately diagnosed by these methods. However, one family did not show a VHL gene mutation in the germ line but showed a somatic mutation at exon 2 in the hemangioblastoma tissue. The consequence of the somatic mutation was a microdeletion leading to a frameshift mutation. Our study is the first report of VHL gene analyses of Japanese VHL disease families, and suggests that not only germ line mutation, but also somatic mutation can lead to development of a tumor associated with the VHL disease.
Base Sequence↗
Uptake and intracellular activity of AM-1155 in phagocytic cells.
The uptake and intracellular activity of AM-1155 in murine J774.1 macrophages and human polymorphonuclear leukocytes were investigated. AM-1155 penetrated phagocytic cells rapidly and reversibly, although the penetration process was not affected by metabolic inhibitors such as sodium fluoride, cyanide m-chlorophenylhydrazone, or ouabain or by nucleoside transport system inhibitors such as adenosine. The intracellular concentration-to-extracellular concentration ratio of AM-1155 in both cell types of phagocytes ranged from 5 to 7. These ratios were almost equal to those for sparfloxacin. The intracellular activity of AM-1155 in J774.1 macrophages, examined with Staphylococcus aureus 209P as a test bacterium, was dependent on the extracellular concentration. AM-1155 at a concentration of 1 microgram/ml reduced the number of viable cells of S. aureus ingested by more than 90%. The intracellular activity of AM-1155 was more potent than those of sparfloxacin, ofloxacin, ciprofloxacin, flomoxef, and erythromycin. These results suggest that the potent intracellular activity of AM-1155 might mainly be due to the high intracellular concentration and its potent in vitro activity.
Animals↗
A quantitative analysis of testosterone action on FSH secretion from individual pituitary cells using the cell immunoblot assay.
We investigated the effects of testosterone on FSH secretion from male rat anterior pituitary cells in culture at the single cell level. Anterior pituitary cells cultured with or without 10 ng/ml testosterone for 72 h were mono-dispersed and subjected to cell immunoblot assays for FSH. Cell blots specific for FSH were quantified by means of a microscopic image analyzer. The number of FSH-secreting cells detected as immunoreactive cells blots on the transfer membrane represented 4.1% of total pituitary cells applied on the membrane. The amount of FSH secreted by single cells varied from < 20 to > 8,000 fg/cell/h. The number of FSH-secreting cells was not changed by the addition of 10 ng/ml testosterone into the culture medium. Testosterone administration increased the mean FSH secretion by 64% after 3 h incubation, resulting in a shift to the right in the frequency distribution of FSH secretion from single cells. The total amount of FSH, namely the sum of FSH secreted by each FSH-secreting cel, was increased by 92% by the addition of testosterone. However, mean amounts of FSH secretion by the top ten cells of the largest secretor subgroup (> 5 pg/cell/3 h) were not different between control and testosterone-treated groups. The present study analyzed, for the first time, FSH secretion from rat anterior pituitary cells at the single cell level. The results suggest that stimulation by testosterone of FSH secretion in vitro is not due to an increase in the number of FSH-secreting cells but to an increase in FSH secretion from each cell.
Animals↗
[Usefulness of newly developed subcutaneous one point lifting method in gynecological laparoscopic operation].
We first introduced the abdominal wall lifting method in gynecological laparoscopic operations in 1994. Now we have developed a new one-point lifting technique (Tokyo Medical College method) that enables gynecological laparoscopic operations to be performed more safely, easily and economically. 1. The TMC method provides a sufficiently spacious operative field in the same way as artificial pneumoperitoneum and can overcome the negative influence of obesity on the operative field. 2. Because the abdominal wall is lifted up by means of a single stainless steel wire passed under the skin in this method, the limitations of previous methods are completely overcome. Furthermore setting up for this method is very easy and can be completed in a short time. 3. Because the aperture for the Surgigrip made in the abdominal wall is short and has a large internal diameter, we can manipulate operative instruments freely. Especially suturing and ligation can be carried out simply and accurately. 4. We were able to continue irrigation and suction without deterioration of the operative field and to easily remove resected tissue from the abdominal cavity. 5. The frequency of intracorporeal suture and ligation in this method increased significantly compared with the pneumoperitoneum method in cases of ovarian diseases. As a result, most operative procedures in ovarian diseases became cystectomies, preserving the healthy part of the ovary. This also reduced operative cost by avoiding expensive autosuture equipment. 6. There were no complications such as subcutaneous bleeding with this method. There was no significant difference between this method and pneumoperitoneum in terms of postoperative pain. The TMC method is a new laparoscopic operative technique that allows procedures to be performed under conditions close to laparotomy procedures and solves most of the problems of the pneumoperitoneum method.
Abdominal Muscles↗
Prognostic significance of Ki-67 labeling index in urothelial tumors of the renal pelvis and ureter.
PURPOSE: We evaluated the prognostic significance of the Ki-67 labeling index in 70 patients with primary urothelial tumors of the renal pelvis and ureter. MATERIALS AND METHODS: Immunohistochemical staining for Ki-67 in archival tumor materials was done by the streptavidin-biotin method. RESULTS: Univariate survival analysis showed that the prognosis of patients with a high Ki-67 labeling index of 21.7 or more was significantly worse than that of patients with an intermediate labeling index of 13.3 to less than 21.7 (p < 0.01) or a low labeling index of less than 13.3 (p < 0.001). Multivariate survival analysis showed that staining for Ki-67 labeling index was significantly correlated with prognosis (p < 0.01). CONCLUSIONS: Analysis of Ki-67 labeling index provides useful prognostic information about patients with primary urothelial tumors of the renal pelvis and ureter.
Antigens, Neoplasm↗
[Combination therapy with estrogen and UFT in newly diagnosed prostatic cancer (poorly differentiated, stage D2)].
To determine whether long-term oral administration of UFT, a combination of 5-fluorouracil and uracil, in addition to conventional estrogen therapy improved the response and survival of the patients with advanced stage D2 prostate adenocarcinoma, a randomized prospective study was performed with either estrogen alone (Honvan 200 mg/day or presexol 1 mg/day: group A) or estrogen plus UFT (400 mg/day:group B). This study comprises 34 newly diagnosed patients with poorly differentiated prostatic adenocarcinoma (18 patients in group A and 16 in group B). Survival from all causes of death or cancer-specific death were compared using Kaplan-Meier actual methods among the patients separated by histological composition of tumors analyzed WHO histologic patterns, score of extent of disease (EOD), and with or without normalization of serum PSA or PAP levels after treatment. Although combination therapy with UFT against overall survival was effective without statistical significance, better survival in this group than the patients treatment with estrogen alone assessed among the patients whose tumor contained more than 70% of medullary and/or column-cord histological components. The survivals among the patients with EOD score 3 and whose serum PSA or PAP levels did not lead to decrease within normal levels after treatment were also better in group B than in group A. These findings suggest the validity of the combination therapy with UFT in addition to estrogen against highly advanced prostatic cancer patients whose tumor composed of abundant non-hormone-refractor histological components.
Adenocarcinoma↗
Hydronephrosis and hydroureter with extremely high levels of serum carbohydrate antigens 19-9 and SPan-1: a case report.
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Antigens, Neoplasm↗
Loss of heterozygosity at the p53, RB, DCC and APC tumor suppressor gene loci in human bladder cancer.
PURPOSE: Allelic losses within several tumor suppressor genes have been detected frequently in various types of human cancer. We investigated the roles and possible interactions of the tumor suppressor genes p53, Rb, DCC and APC in bladder cancer. MATERIALS AND METHODS: Loss of heterozygosity (LOH) of these 4 genes was examined in 45 human bladder cancers by polymerase chain reaction and restriction fragment length polymorphism assay. RESULTS: Of the evaluated cases, LOH was seen at P53 in 38%, at Rb in 22%, at DCC in 36% and at APC in 6% of tumors. Loss of heterozygosity at p53 and Rb was predominantly observed in high grade (grade 3) and/or invasive (T2 or greater) tumors, whereas LOH at DCC was present irrespective of tumor grade and stage. Allelic losses at either p53, Rb, DCC or APC were seen in 82% of high grade tumors, but in only 21% of low grade (grade 1 and 2) tumors (p<0.005). Similarly, 71% of invasive tumors had LOH at one or more loci compared with 20% of superficial (Ta and T1) tumors (p<0.005). Interestingly, p53-LOH and Rb-LOH were often observed simultaneously in the same tumor. CONCLUSIONS: These results suggest that loss of the p53, Rb and/or DCC genes is involved in most of the late and some of the early steps of bladder carcinogenesis.
Base Sequence↗
[A case of hydronephrosis with high level of serum Span-1 antigen and CA19-9].
A sixty-year-old woman visited our hospital with a complaint of left flank pain. Laboratory data showed a high level of serum CA19-9. Computerized tomography and ultrasonography revealed left hydronephrosis and hydroureter. No tumors were found in the liver, pancreas, gallbladder, gastrointestinal tract or genitourinary tract. The serum SPan-1 antigen level was elevated to 250 U/ml, and the serum CA19-9 level was also elevated to 580 U/ml. Since urological malignancy was not excluded from these findings, left nephroureterectomy was performed. Pathological findings revealed chronic inflammation, and malignant cells were not found in the resected specimens. Although high levels of SPan-1 antigen and CA19-9 have been reported in benign diseases, both are usually less than 100 U/ml. In this case, serum SPan-1 antigen and CA19-9 levels were extremely high (more than 1,000 U/ml). Since the serum SPan-1 antigen and CA19-9 levels were gradually reduced to normal levels within 4 months after the operation, a possible explanation for the high levels of the two tumor markers is hydronephrosis in the left kidney. We report this interesting hydronephrosis associated with high levels of serum SPan-1 antigen and CA19-9.
Antigens, Neoplasm↗
[Recurrent and up-grading bladder cancer in a young female: a case report].
We report a case of superficial bladder cancer in a young female, with grade-up tumor after frequent recurrences. A 29-year-old woman complained of gross hematuria on April 25, 1991. Cystoscopic examination revealed a papillary pedunculated tumor and transurethral resection of bladder tumor (TUR-BT) was performed. Pathological examination showed transitional cell carcinoma (TCC) pT1 grade 1. In spite of prophylactic therapy, such as intravesical instillation of anticancer drugs and radiochemohyperthermia, she suffered frequent recurrences. At the 6th recurrence, the tumor deteriorated to grade 3 on September 2, 1992. Total cystectomy was done on February 15, 1993 because of uncontrollable bleeding from bladder cancer. Convalescence was uneventful, and no evidence of recurrence was present 2.8 years postoperatively.
Adult↗
[Clinical early phase II study of bicalutamide (Casodex) in patients with prostatic cancer].
To investigate the efficacy and safety of bicalutamide (Casodex) with its clinically recommended dose, the randomized early phase II study was performed in 124 patients with prostatic cancer (stage C, D). The patients were given 50, 80 or 100 mg of bicalutamide orally once a day in fixed doses for 12 weeks; 122 patients were eligible for evaluation. The overall response rate was 50.0% (20/40), 61.0% (25/41) and 53.7% (22/41) in the 50 mg, 80 mg and 100 mg groups, respectively. The response rate in prostate lesion, bone and lymph node metastases was slightly higher in the 80 mg group than in the 50 mg and 100 mg groups. The proportion of patients showing a response with regard to serum PSA (CR and PR) was 84.2, 92.7 and 97.6% in the 50, 80 and 100 mg groups, respectively. The incidence of adverse reactions was 65.0, 61.0 and 61.0% in the 50, 80 and 100 mg groups, respectively, and there was no significant difference in overall safety rating in the three groups. Frequent adverse reactions were gynecomastia and breast pain. Only one patient in the 80 mg group was withdrawn due to shortness of breath. Serum concentrations of LH, testosterone and estradiol increased significantly after treatment. Bicalutamide was concluded to be effective and well tolerated in patients with prostatic cancer, and its recommended dose was 80 mg once daily.
Administration, Oral↗