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Kazunori Kihara

Publications and source records attributed to Kazunori Kihara.

At least 19 recordsLinked to original sources
PubMed2004

C-H to N substitution dramatically alters the sequence-specific DNA alkylation, cytotoxicity, and expression of human cancer cell lines.

We designed and synthesized sequence-specific alkylating conjugates 1 and 2, which selectively alkylate matched sequences at nanomolar concentrations. Conjugates 1 and 2 differ only in that the C-H is substituted by an N in the second ring, which precisely recognizes and effectively alkylates DNA according to the recognition rule of Py-Im polyamides. We investigated sequence-specific DNA alkylation, cytotoxicity in 39 human cancer cell lines, and the effect on expression levels in cancer cell lines by Py-Im conjugates 1 and 2. The COMPARE analysis of the mean graphs showed that conjugates 1 and 2 did not correlate well with each other (r = 0.65) despite having a common DNA alkylating mechanism (purine N3 alkylation). Array-based gene expression analysis demonstrated that there are several oppositely regulated genes. The results suggest the intriguing possibility that DNA alkylating agents recognizing longer base-pair sequences may provide a promising approach for developing new types of antigene agents.

Alkylation↗
PubMed2004

Regulation of prostate-specific antigen by activin A in prostate cancer LNCaP cells.

Activins are multifunctional growth and differentiation factors and stimulate FSH-beta gene expression and FSH secretion by the pituitary gonadotropes. Follistatins bind activin, resulting in the neutralization of activin bioactivity. The activin/follistatin system is present in the prostate tissue. Prostate-specific antigen (PSA) plays an important role in male reproductive physiology as well as being very important as a tumor marker for prostate cancer. Thus the regulation of PSA has important clinical implications. Previous studies showed that PSA is primarily regulated by androgens. In the present study, we evaluated the direct effects of activin A on the proliferation and PSA production of prostate cancer LNCaP cells, which express functional activin receptors and androgen receptor and PSA. LNCaP cells were treated with activin A and 5alpha-dihydrotestosterone (DHT) with or without their antagonists (follistatin or the nonsteroidal anti-androgen bicalutamide). Activin A decreased cell growth of LNCaP cells in a dose-dependent manner, whereas DHT increased it in a biphasic manner. In contrast to their opposing actions on cell growth, both activin A and DHT upregulated PSA gene expression and increased PSA secretion by LNCaP cells. The effects of activin A and DHT to increase PSA production were synergistic or additive. Follistatin or bicalutamide was without effect on cell growth or PSA production. The effects of activin A on LNCaP cells were blocked by follistatin, not by bicalutamide, whereas effects of DHT were prevented by bicalutamide, not by follistatin. Activin A upregulates PSA production, and the effect is through an androgen receptor-independent pathway. The activin/follistatin system can be a physiological modulator of PSA gene transcription and secretion in the prostate tissue, and activins may cooperate with androgen to upregulate PSA in vivo.

Activins↗
PubMed2004

Modulation of intrinsic cavernous tone and nitric oxide production by arginase in rabbit corpus cavernosum.

PURPOSE: Arginase shares the common substrate L-arginine with nitric oxide synthase (NOS). We investigated the roles of NOS and arginase for modulating intrinsic and vasoconstrictor tone in rabbit corpus cavernosum (RCC). MATERIALS AND METHODS: Isolated RCC tissues were used for isometric tension experiments, and NOS and arginase activities. The endothelium lining RCC lacunar spaces was disrupted and/or removed by saponin treatment. RESULTS: Following stretch of approximately 1gm NG-nitro-L-arginine methyl ester (L-NAME) as a NOS inhibitor caused endothelium dependent contraction, while the potent and specific arginase inhibitor N omega-hydroxy-nor-L-arginine (nor-NOHA) caused endothelium dependent relaxation. Relaxation with nor-NOHA was reversed by L-NAME. In the presence of 10 mM L-arginine 0.1 mM nor-NOHA was ineffective. Pretreatment with 0.1 mM L-NAME and 0.1 mM nor-NOHA did not significantly affect the vasoconstrictor response to phenylephrine. The magnitude of contraction with 0.1 mM L-NAME and relaxation with 0.1 mM nor-NOHA during contraction induced by phenylephrine were not significantly different from changes with L-NAME and nor-NOHA under intrinsic basal tone. In the enzymatic study NOS and arginase were detectable in cavernous homogenates. Nor-NOHA inhibited arginase but not NOS activity. CONCLUSIONS: Results indicate that basal nitric oxide production from the endothelium regulates intrinsic cavernous tone and endogenous arginase activity in the endothelium modulates tone by inhibiting nitric oxide production, presumably through competition with constitutive NOS for the common substrate L-arginine.

Animals↗
PubMed2004

Prognostic significance of endothelial Per-Arnt-sim domain protein 1/hypoxia-inducible factor-2alpha expression in a subset of tumor associated macrophages in invasive bladder cancer.

PURPOSE: Endothelial Per-Arnt-Sim domain protein 1 (EPAS1) is induced under hypoxia and it transactivates a series of genes involved in angiogenesis and energy metabolism. Recent studies showed that EPAS1 is expressed in tumor associated macrophages (TAMs), which have multifaceted roles in tumor progression. We hypothesized that EPAS1 expressed in TAMs may contribute to bladder cancer progression. MATERIALS AND METHODS: Clinicopathological and followup data on 69 patients undergoing radical cystectomy for T1-4N0-2M0 high grade bladder urothelial carcinoma were reviewed. Quantitative immunohistochemical analysis of TAMs and EPAS1 was performed separately in invasive front and in other superficial parts of carcinoma tissues. TAM counts and EPAS1 positive cell counts were compared with pathological variables and cancer specific survival (CSS). RESULTS: The 5-year CSS rate in the 69 patients was 69% at a median followup of 58 months (range 2 to 196). EPAS1 expression was restricted to a small subset of TAMs. Although TAM counts were not associated with T stage or lymph node metastasis, EPAS1 expressing TAM counts were significantly associated with higher T stage. On univariate and multivariate analyses higher EPAS1 expressing TAM counts in invasive front along with higher T stage and positive lymph node metastasis were significantly associated with shorter CSS, while total TAM counts or EPAS1 expressing TAM counts in other superficial parts did not. CONCLUSIONS: Despite limited prognostic effects of total TAMs EPAS1 expressing TAMs were associated with a poor prognosis of invasive bladder cancer, suggesting that EPAS1 expressed in a subset of TAMs mediates bladder cancer progression.

Adult↗
PubMed2003

Impaired p63 expression associates with poor prognosis and uroplakin III expression in invasive urothelial carcinoma of the bladder.

PURPOSE: p63 is proposed to play roles in normal development and differentiation of stratified epithelia including urothelium. We recently reported that impaired p63 expression is a common feature of high-grade invasive urothelial carcinomas and associates with reduced beta-catenin. On the basis of these facts, we proposed that impaired p63 expression contributes to biological aggressiveness of urothelial neoplasms. Uroplakin (UP) III expression was also evaluated to investigate a possible association between loss of p63 expression and terminal urothelial differentiation. EXPERIMENTAL DESIGN: Expression of p63, beta-catenin, and UP III was immunohistochemically analyzed in 75 cystectomy specimens of high-grade invasive bladder carcinoma. p63 expression was semiquantified and compared with pathological parameters, expression of beta-catenin and UP III, and cancer-specific survival. RESULTS: Lower p63 expression was significantly associated with higher Tumor-Node-Metastasis (TNM) stage (P = 0.0004), lymph-node metastasis (P = 0.013), and reduced beta-catenin expression (P = 0.003). By univariate analysis, lower p63 expression, along with TNM stage and lymph-node status, were significantly associated with a poor prognosis (P = 0.0005), whereas reduced beta-catenin was not. By multivariate analysis, the prognostic effect of p63 expression was independent of TNM stage and lymph-node status with marginal statistical significance (P = 0.074). UP III expression was restricted to a subset of p63-negative carcinoma cells, including even anaplastic carcinoma cells. CONCLUSIONS: Impaired p63 expression characterizes biological aggressiveness of high-grade invasive urothelial carcinomas. Moreover, loss of p63 expression is a prerequisite for UP III expression. Our data suggest that p63 plays critical roles in tumor progression and biochemical terminal differentiation of urothelial neoplasms.

Adult↗
PubMed2003

Control of canine membranous urethra, bulbocavernosus and ischiocavernosus muscles by lumbosacral sympathetic pathways.

The membranous urethral muscles, bulbocavernosus muscle (BCM) and ischiocavernosus muscle (ICM) play a significant role on expulsion at ejaculation. Projection of the sympathetic pathways in the retroperitoneum to these muscles was investigated in the dog. Intraluminar pressure of the membranous urethra and contractions of the BCM and ICM to electrical stimulation of the lumbar splanchnic nerve (LSN) or the lumbosacral sympathetic chain (LSC) were examined. Stimulation of the LSN was performed after transection of the unilateral hypogastric nerve (HGN) to clarify its cross-innervation. Stimulation of each of the 2nd to 4th LSNs elicited elevation of the intraluminal pressure of the membranous urethra. In eight dogs whose right HGNs were transected, 15 of the 19 right LSNs, and 12 of the 16 left LSNs examined elicited elevation of the membranous urethral pressure, respectively. In five dogs whose left HGNs were transected, 6 of the 9 right LSNs and 10 of the 12 left LSNs stimulated elicited elevation of the pressure. Stimulation of the HGN caused no detectable contractions of the BCM and ICM in all six dogs examined. Stimulation of the LSC elicited responses of the BCM and ICM in all six dogs examined and the membranous urethra in three of six dogs. The maximum value of the response of the BCM was greater than that of the ICM. After consecutive transection of the ipsilateral pelvic nerve, stimulation of the LSC showed no significant changes in the responses of the BCM and ICM. The above results indicate the following: (1). each of the L2-L4 LSNs sends signals to the membranous urethra via two routes, passing through the ipsilateral or contralateral HGN; (2). the above nerve does not send effective signals to the BCM and ICM; (3). the LSC sends signals to the membranous urethra, BCM and ICM; (4). the signals from the LSC mainly pass through the pudendal nerve to the BCM and ICM; and (5). the signals were dominant to the BCM compared with the ICM.

Animals↗
PubMed2003

Successful long-term disease-free survival following multimodal treatments in a patient with a repeatedly recurrent refractory adrenal cortical carcinoma.

A 47-year-old male patient underwent surgery for a 10-cm adrenal cortical carcinoma. A large invasive adrenal mass was surgically removed en bloc with the right kidney and the lower lobe of the liver. Two months postoperatively, a 7-cm recurrent mass developed in the right psoas muscle. After a partial response was achieved by irradiation (40 Gy) and high-dose chemotherapy (carboplatin and etoposide) with peripheral blood stem cell transplantation, the patient underwent surgery with a wide excision of the psoas muscle. Twelve months after the initial surgery, an 8-cm rib metastasis developed and the patient again underwent surgery after a combination of irradiation (50 Gy) and chemotherapy (cisplatin and etoposide). The patient has been doing well without any evidence of recurrence for 5 years. Refractory or metastatic adrenal cortical carcinomas have been thought to be lethal, therefore, the present case provides support for multimodal treatments of refractory adrenocortical cancers.

Adrenocortical Carcinoma↗
PubMed2003

Adenocarcinoma arising at the ileoileal anastomotic site of Scheele's ring.

Most tumors arising after augmentation ileocystoplasty have been reported to develop adjacent to the ileovesical anastomosis. Herein, we report a case of adenocarcinoma arising at the ileoileal anastomotic site 33 years after augmentation ileocystoplasty (Scheele's ring plasty) for tuberculous contracted bladder. The present case shows the possibility of late malignancy developing at the ileoileal junction after ileal neobladder.

Adenocarcinoma↗
PubMed2003

Favorable outcome of preoperative low dose chemoradiotherapy against muscle-invasive bladder cancer.

To investigate the feasibility of preoperative low-dose chemoradiotherapy, 50 patients with localized muscle-invasive bladder cancer (T2-T4) were treated with concurrent cisplatin (100 mg/body x 2 courses) and pelvic irradiation (40 Gy). Among 20 patients (40%) who achieved clinical complete regression, 11 with solitary tumor underwent partial cystectomy because of advanced age, poor condition of the patients, or a reluctance to have radical surgery. Radical cystectomy was carried out in the remaining 39 cases (complete regression 9, partial regression 30). Pathologic T0 response (no residual tumor) was achieved in 18 (36%) of all the cases. Median follow-up was 19 months (range 2-59 months). Estimated 3-year disease-free survival was 75% for all patients and 100% for T0 responders. Local recurrence (2 patients) or distant metastasis (6 patients) developed in 8 of 32 patients with pathologic persistent tumor. All of the 11 patients (9 with T0 response and 2 with a small residual tumor nest) who underwent partial cystectomy were recurrence free for observation periods up to 59 months. Low-dose chemoradiotherapy is as effective as other neoadjuvant protocols and is applicable to high-risk patients. The bladder can be preserved by partial cystectomy in selected cases with clinical complete regression.

Aged↗
PubMed2003

Roles of accumulated endogenous nitric oxide synthase inhibitors and decreased nitric oxide synthase activity for impaired trigonal relaxation with ischemia.

PURPOSE: We examined whether endogenous nitric oxide (NO) synthase (NOS) inhibitors are involved in the impaired trigonal relaxation with ischemia in rabbits. MATERIALS AND METHODS: Rabbits were divided into control and ischemia groups. Two weeks after partial vessel occlusion strips of trigone and detrusor were processed to determine endogenous methylarginines and L-arginine by automated high performance liquid chromatography. We also compared NOS activity and NO mediated functional responses to electrical field stimulation between 2 groups. RESULTS: Neurogenic and NO but not sodium nitroprusside induced mediated relaxation in the trigone were significantly impaired following ischemia. Ca2+ dependent NOS activity, and baseline and stimulated cyclic guanosine monophosphate production with electrical field stimulation were significantly decreased following ischemia. The contents of L-NMMA (NG-monomethyl-L-arginine) and asymmetrical ADMA (NG, NG-dimethyl-L-arginine) but not L-arginine or symmetrical SDMA (NG, N'G-dimethyl-L-arginine) were increased in the trigone following ischemia. Authentic L-NMMA and ADMA but not SDMA inhibited neurogenic relaxations in a concentration dependent manner without affecting the relaxation produced by sodium nitroprusside in control tissue. Excess L-arginine abolished L-NMMA and ADMA inhibition. CONCLUSIONS: These results suggest that impaired NO mediated trigonal relaxation following ischemia is closely related to decreased NOS activity and the increased accumulation of L-NMMA and ADMA.

Animals↗
PubMed2003

[Fibroepithelial polyp of the anterior urethra, found during post-operative follow-up of ureteral cancer].

A 52-year-old man underwent nephroureterectomy against left distal ureteral cancer (transitional cell carcinoma, Grade 2, pTa), and was followed up by surveillance alone. Twenty-two months postoperatively, a pedunculated tumor was found in the anterior urethra by cystourethroscopy. Pathological examination of the tumor resected transurethrally revealed a fibroepithelial polyp. There have been only twelve cases of fibroepithelial polyp of the anterior urethra reported in the literature. Since 4 out of 8 adult cases among them were found during the postoperative follow up period of urothelial cancer, mechanical irritation by repeated transurethral procedures might be responsible for the development of fibroepithelial polyp of the anterior urethra in these cases. If anterior urethral tumor is found during follow-up urothelial carcinoma, benign urethral polyp should be considered in the differential diagnosis.

Carcinoma, Transitional Cell↗
PubMed2003

[A case of fibroepithelial ureteral polyp in an adult patient].

A 24-year-old man complaining of asymptomatic gross hematuria was referred to our hospital for treatment of bilateral hydronephroses (left > right) diagnosed at a previous clinic. Radiological examinations demonstrated a filling defect at the left uretero-pelvic junction. Cytological examination of the urine was negative. With the diagnosis of suspected benign ureteral polyp, the patient underwent endoscopic-assisted partial ureterectomy and pyeloplasty through a 5 cm flank incision. Histological examination revealed that the villous tumor in the ureter was a fibroepithelial polyp.

Adult↗
PubMed2003

[Cyclophosphamide-induced bladder cancer: three case reports].

Three cases of cyclophosphamide (CPM)-induced transitional cell carcinoma (TCC) of the bladder are reported. A 36-year-old female (case 1) and a 63-year-old male (case 2) received CPM at total doses of 104 g and 100 g, respectively, for the therapy of Wegener's granulomatosis. A 50-year-old female (case 3) received CPM at a dose of 57 g for the therapy of recurrent breast cancer. They visited our institute with the chief complaint of macrohematuria. In all cases, cystoscopy revealed bladder tumor with hemorrhagic cystitis. They underwent transurethral resection of bladder tumor. Histological examination revealed grade 2 TCC in cases 1 and 2 and grade 3 TCC in case 3. All patients underwent intravesical instillation of Mitomycin C with or without hyperthermia. Including our 3 cases, 17 cases of CPM-induced bladder tumor have been reported in the Japanese literature.

Administration, Intravesical↗
PubMed2003

[A case of idiopathic adrenal hemorrhage].

A 67-year-old woman underwent abdominal ultrasonography as part of a general health examination and was incidentally found to have a mass 5 cm in diameter in the left adrenal gland. She had no experience of abdominal trauma. Computerized tomography (CT) revealed a 5.5 x 5.0 cm mass in the left adrenal gland, which was heterogeneously enhanced by the contrast medium. Hormanal data for adrenal function were all within the normal range. For the suspected non-functioning adrenal tumor, the patient underwent adrenalectomy. Histopathological examination demonstrated only hematoma without tumor cells.

Adrenal Gland Diseases↗
PubMed2003

[A case of non-functioning adrenocortical adenoma associated with renal cell carcinoma].

Left renal and left adrenal masses were incidentally found by computerized tomography (CT) in a 56-year-old man who was admitted to our hospital for treatment of upper digestive tract hemorrhage. Apparently no clinical signs suggestive of Cushing's syndrome existed. The renal tumor was diagnosed as renal cell carcinoma based on the findings on enhanced CT. 131I-adosterol uptake in the examination of adrenal scintigraphy under dexamethasone suppression was definitely increased in the left adrenal gland, although hormonal examinations of serum and urine for adrenal functions were within the normal range. Plasma adrenocorticotropic hormone (ACTH) and serum cortisol were suppressed by administration of 2 mg dexamethasone for 2 days. The left kidney was radically removed by surgery together with the left adrenal gland. Histological diagnoses were left renal cell carcinoma and adrenocortical adenoma.

Adrenal Cortex Neoplasms↗