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Hitoshi Inoue

Publications and source records attributed to Hitoshi Inoue.

At least 19 recordsLinked to original sources
PubMed2006

Inhibition of glutathione synthesis overcomes Bcl-2-mediated topoisomerase inhibitor resistance and induces nonapoptotic cell death via mitochondrial-independent pathway.

Bcl-2 protein plays a critical role in inhibiting anticancer drug-induced apoptosis. We found that Bcl-2 overexpression is associated with a nearly 3-fold increase in cellular glutathione levels and with increased resistance to cell death after treatment with etoposide or SN-38, a derivative of camptothecin, in leukemia 697 cells with wild-type p53. Treatment of Bcl-2-overexpressing 697 cells (697-Bcl-2) with buthionine sulfoximine (BSO), an inhibitor of glutathione synthesis, reduced cellular glutathione levels and completely abolished Bcl-2-mediated drug resistance. Morphologic studies revealed that nonapoptotic cell death was induced in 697-Bcl-2 cells after treatment with BSO plus etoposide or SN-38. Activation of caspase-3/7 and cytochrome c release could not be detected in 697-Bcl-2 cells after these drug treatments. Notably, we showed that proteasome-mediated down-regulation of Puma and Noxa proteins occurs in 697-Bcl-2 cells after treatment with BSO plus topoisomerase inhibitor, although there is an increase in the protein levels of p53 in these 697-Bcl-2 cells. In contrast, parental 697 cells underwent typical apoptosis with up-regulation of Puma and Noxa proteins, followed by cytochrome c release and caspase-3/7 activation after treatment with topoisomerase inhibitor in the presence or absence of BSO. Our data suggest that BSO may possess a unique activity to overcome Bcl-2-mediated drug resistance by stimulating the signals that can bypass mitochondrial process in Bcl-2-overexpressing cells.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2006

The expression of thymidine phosphorylase is a prognostic predictor for the intravesical recurrence of superficial bladder cancer.

BACKGROUND: Thymidine phosphorylase (TP), also known as platelet-derived endothelial cell growth factor, has been implicated in the angiogenesis of bladder cancer. The aim of this study is to investigate the association between TP expression and the clinicopathologic findings, and the prognostic value. METHODS: TP immunohistochemical staining was performed in specimens from 71 patients (50 men and 21 women) with superficial bladder cancer (pTa or pT1). Thirty-nine patients had received intravesical instillation of tetrahydropyranyladriamycin (THP) after transurethral resection (TUR) and the other 32 had not. For immunohistochemistry, paraffin-embedded specimens were stained with mouse monoclonal antibody against TP. When more than 10% of tumor cells were positively stained, staining was defined as positive. The correlations between TP immunostaining and clinicopathological features were analyzed. Multivariate analysis, using the Cox proportional hazard model, was performed to determine the risk factors for intravesical recurrence. RESULTS: Specimens from 29 of the 71 patients (19 men and 10 women) were positive for TP. The expression of TP was not correlated with age, sex, histological grade, multiplicity, or morphology. Also, TP expression was not associated with whether the cases were primary or recurrent. Multivariate analysis demonstrated that the decreased expression of TP and the use of THP instillation could be independent predictors of a higher rate of intravesical recurrence-free bladder cancer. CONCLUSION: The present study suggests that immunohistochemical TP staining is useful for predicting the intravesical recurrence of superficial bladder cancer after Transurethral resection of bladder tumor (TUR-Bt).

Administration, Intravesical↗
PubMed2006

Possible correlation between polymorphism in the tumor necrosis factor-beta gene and the clinicopathological features of bladder cancer in Japanese patients.

OBJECTIVES: In a variety of cancers, several polymorphisms of the tumor necrosis factor (TNF) genes have been reported to result in different clinical outcomes. We investigated whether a polymorphism of the TNF gene is associated with a susceptibility to bladder cancer and its disease status. METHODS: Polymorphisms in the TNF-alpha gene promoter (-308 bp) and the NcoI site in the first intron of the TNF-beta gene were analyzed in 141 Japanese patients with bladder cancer and 173 Japanese controls by polymerase chain reaction-restriction fragment length polymorphism. The correlations between the polymorphisms of the TNF genes and the clinicopathological features were analyzed. RESULTS: The number of cases and controls with TNF-alpha2 was too small to be assessable. In contrast, the TNF-beta1/2 genotype at the NcoI site in the first intron conferred a 1.71-fold increased risk of bladder cancer compared to the TNF-beta2/2 genotype. In the bladder cancer group, patients with the TNF-beta1 allele had a significantly higher risk for a high-grade tumor (grade 3) or carcinoma in situ (CIS) than those without the TNF-beta1 allele. Moreover, in the superficial bladder cancers, patients with the TNF-beta1 allele showed a significantly higher intravesical recurrence rate than those without the TNF-beta1 allele. CONCLUSION: This polymorphism in the TNF-beta gene appears to be associated with tumor occurrence and disease status, such as the tumor grade and the presence of CIS. Further study with an increased sample size is warranted.

Adult↗
PubMed2006

[Adrenal ganglioneuroma in a 14-year-old girl: a case report].

A 14-year-old girl was referred to our hospital for examination of a right adrenal tumor, incidentally found by abdominal ultrasound sonography. Computed tomographic scan and magnetic resonance imaging showed a 44 x 20 mm solid tumor in the right adrenal region. Endocrinological examination were within normal limits except for slightly increased serum aldosterone. Laparoscopic adrenalectomy was performed and the tumor was histologically diagnosed as ganglioneuroma originated from the right adrenal medulla.

Adolescent↗
PubMed2006

[Pelvic lymph node metastasis from bladder cancer markedly responsive to methotrexate vinblastine doxorubicin and cisplatin (M-VAC) therapy followed by radiotherapy: a case report].

We report a case of bladder cancer with pelvic lymph node metastasis effectively treated by chemotherapy followed by radiotherapy. The patient was a 65-year-old man who had undergone radical cystectomy. Histological findings showed urothelial carcinoma, G3 > G2, pT1b. After 31 months, computerized tomography (CT) revealed a bulky tumor (7.0 x 5.6 cm) along the left pelvic wall, indicating pelvic lymph node metastasis. Five courses of chemotherapy consisting of M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin) was performed. The size of the tumor was reduced to 1.5 x 1.0 cm. Then, external beam radiotherapy (50 Gy) was added to the residual tumor. He has been alive with no evidence of disease progression for 31 months since the radiotherapy.

Aged↗
PubMed2005

KIT (c-kit oncogene product) pathway is constitutively activated in human testicular germ cell tumors.

We investigated the expression of KIT (product of c-kit oncogene), gain-of-function mutations, and activation of its downstream signal transduction in human testicular cancers. KIT was expressed in 88% (22/25) of seminomas and in 44.4% (4/9) of non-seminomas compared to adjacent normal testicular tissue. Nine of the KIT-expressing seminomas had mutations (40.9%; 9/22) in the c-kit gene; two cases in exon 11 and 7 cases in exon 17. Two of these mutations in exon 17 were novel, and the other seven mutations were identical to the already known gain-of-function mutations which cause activation of KIT without ligand stem cell factor. All of the mutant KIT and 53.8% (7/13) of wild-type KIT were phosphorylated (activated) and associated with phosphorylated phosphatidylinositol 3-kinase (PI3K). Akt was also phosphorylated in these seminomas, suggesting that the KIT-PI3K-Akt pathway is activated in seminoma. These findings suggest that the KIT-PI3K-Akt pathway is constitutively activated in testicular germ cell tumors, due to overexpression of KIT protein and/or gain-of-function mutations in the c-kit gene.

Adult↗
PubMed2005

Prostate cancer mediates osteoclastogenesis through two different pathways.

The present study was undertaken to test the effects of prostate cancer cell lines (LNCaP, DU145, PC3, and MDA PCa 2b) on osteoclastogenesis. Crude conditioned medium (CM) from all four prostate cancer cell lines enhanced expression of the mRNA for receptor activator of NF-kappaB ligand (RANKL) in a mouse osteoblast cell line, MC3T3-E1; however, CM had no effect on expression of osteoprotegerin (OPG) mRNA. Coculture of MC3T3-E1 with prostate cancer cells yielded similar results. The number of mature osteoclasts induced by soluble RANKL increased significantly when osteoclast precursor cells were cultured with CM from LNCaP and DU145 cells. CM from LNCaP and DU145 cells also induced maturation from precursor in the absence of soluble RANKL, and this effect was not blocked by OPG. Addition of CM from DU145 cells increased expression of MMP-9 mRNA by osteoclast precursors. Our findings indicate that prostate cancer mediates osteoclastogenesis through induction of RANKL expression by osteoblasts and through direct actions on osteoclast precursors mediated by some factors other than RANKL.

Bone Neoplasms↗
PubMed2005

[Ureteral polyp resected with a ureteroscope: report of two cases].

Two cases of ureteral polyp resected by a transurethral approach are presented. Case 1: A 70-year-old woman was referred to our clinic because of hydronephrosis incidentally found. Excretory urography demonstrated a filling defect with a long and round smooth contour in the left lower ureter without hydroureter. Urine cytology was negative for malignant cells. Under the clinical diagnosis of left ureteral polyp, polyp was resected transurethrally. The pathological diagnosis was fibroepithelial polyp. Case 2: A 59-year-old woman was referred to our clinic with a chief complaint of macroscopic hematuria. Excretory urography revealed a filling defect with a long and round smooth contour in the left upper ureter. Because urine cytology was negative for malignant cells, left ureteral polyp was suspected. After the operation by tranthurethral approach, the pathological diagnosis was fibroepithelial polyp. No intraoperative complication was observed in either case. Ureteral polyps resected by a transurethral approach are relatively rare. We reviewed and discussed 46 cases of ureteral polyp resected transurethrally, reported in Japan including our two cases.

Aged↗
PubMed2005

[A rare case of transitional cell carcinoma of the ileum segment arising 43 years after ureteroileocystoplasty due to tuberculous bladder atrophy].

A 60-year-old woman visited our hospital complaining of fever up. She had undergone augmentation ileoplasty for tuberculous bladder atrophy 43 years age. Cystoscopy revealed a broadbased tumor on the ileal segment. Histopathological findings of the biopsy specimen demonstrated grade 3 transitional cell carcinoma. She was given 2 courses of chemotherapy (methotrexate, vincristine, adriamicin, cisplatin), but died of metastasis of carcinoma 4 months after diagnosis.

Anastomosis, Surgical↗
PubMed2004

Modulation of the human interleukin-12p40 response by a triazole antifungal derivative, itraconazole.

Some types of antimicrobial agents such as fosfomycin, clarithromycin, and erythromycin have been known to affect the host's immunological response. We investigated whether itraconazole (ITCZ) can modulate the serum cytokine levels (tumor necrosis factor (TNF-alpha, interleukin (IL)-10, IL-12p40) in both patients and healthy subjects. Serum samples were collected and TNF-alpha, IL-10 and IL-12p40 were measured using a sandwich enzyme-linked immunosorbent assay (ELISA). We showed increased levels of IL-12p40 in patients treated with ITCZ. In healthy subjects, moreover, ITCZ treatment significantly increased the production of IL-12p40, but not TNF-alpha or IL-10. These findings suggest that the effectiveness of ITCZ in the treatment of fungal infection may be due not only to its direct antifungal effect, but also to induction of an immunomodulative effect on the host defense systems by regulation of cytokine production.

Adult↗
PubMed2004

Breathing chest radiography using a dynamic flat-panel detector combined with computer analysis.

Kinetic information is crucial when evaluating certain pulmonary diseases. When a dynamic flat-panel detector (FPD) can be used for a chest examination, kinetic information can be obtained simply and cost-effectively. The purpose of this study was to develop methods for analyzing respiratory kinetics, such as movement of the diaphragm and lung structures, and the respiratory changes in x-ray translucency in local lung fields. Postero-anterior dynamic chest radiographs during respiration were obtained with a modified FPD, which provided dynamic chest radiographs at a rate of 3 frames/s. Image registration for correction of physical motion was followed by measurement of the distance from the lung apex to the diaphragm. Next, we used a cross-correlation technique to measure the vectors of respiratory movement in specific lung areas. Finally, the average pixel value for a given local area was calculated by tracing the same local area in the lung field. This method of analysis was used for six healthy volunteers and one emphysema patient. The results reported here represent the initial stage in the development of a method that may constitute a new method for diagnosing certain pulmonary diseases, such as chronic obstructive pulmonary disease, fibroid lung, and pneumonia. A clinical evaluation of our method is now in progress.

Humans↗
PubMed2004

[Squamous cell carcinoma of the urinary bladder after intravesical bacillus Calmette-Guerin therapy for carcinoma in situ: a case report].

A 88-year-old woman presented with bladder tamponade caused by gross hematuria. She had received 2 courses of bacillus-Calmette-Guerin (BCG) intravesical instillation therapy 4 months previously because of the bladder tumor with carcinoma in situ (CIS). Imaging studies and cystoscopy showed a bladder tumor invading into perivesical fat. She underwent total cystectomy and bilateral ureterocutaneostomy on May 27, 2002. Histopathologically, the tumor consisted of squamous cell carcinoma and transitional cell carcinoma.

Administration, Intravesical↗
PubMed2003

Clinical application of the Harmonic Scalpel to allergic rhinitis.

OBJECTIVE: The Harmonic Scalpel (HS) (Johnson & Johnson K.K.) is a surgical tool that allows cutting and coagulation using ultrasonic mechanical vibrations. Its use in the field of otolaryngology has recently been attracting interest. In this study we applied the HS on the inferior nasal concha using a sword shaped blade ('KATANA'). METHODS: Subjects were 20 patients with intractable, perennial allergies that resisted conservative therapy. Subjective symptoms were evaluated as one of five stages, 'symptoms disappeared' 'markedly improved', 'improved', 'unchanged', and 'aggravated'. RESULTS: At the 12th week, 18 patients (90%) with nasal congestion, 16 (80%) with nasal discharge, and 15 (75%) with sneezing had shown at least 'markedly improved'. CONCLUSION: Based on the improvement in subjective symptoms, local and histopathological findings, the HS is an effective surgical modality for these cases. We believe the HS is a safe and useful tool for nasal surgery.

Adolescent↗
PubMed2003

[Development of breathing chest radiography: study of exposure timing].

The flat-panel detector (FPD) has been introduced into clinical practice. A modified FPD, which has the ability to obtain dynamic chest radiographs, was introduced into our hospital, and clinical testing is ongoing. Both the inspiratory and expiratory phases have to be included in dynamic chest radiographs. The purpose of this study was to investigate the most appropriate chest radiography signal for observation of the respiratory process. We prepared ten protocol patterns that differed in terms of respiratory phase at X-ray exposure, exposure duration, and signal multiplicity. We also performed preliminary experiments and administered several questionnaires to ten volunteers. The volunteers breathed according to vocal and visual signals, and their respiratory waves were recorded by spirometer. The most appropriate protocol was similar to the method used for conventional chest radiography.

Adult↗
PubMed2003

Atypical nuclear apoptosis downstream to caspase-3 activation in ara-C treated CCRF-CEM cells.

The necessity of internucleosomal DNA fragmentation for the complete execution of apoptosis is still controversial. While investigating the apoptotic pathway induced by 1-beta-D-arabinofuranosylcytosine (ara-C) in the human T-lymphoblastic leukemia CCRF-CEM (CEM) cells, we could easily retrieve high molecular weight (HMW) DNA fragments with a predominant size of 50 kb. However, under the same circumstances, internucleosomal DNA fragmentation characteristic of apoptosis was undetectable despite estimated heightened caspase-3 activity. Paradoxically, generation of low molecular weight DNA fragments was readily demonstrable by flow cytometric and immunohistochemical evidence in the absence of any detectable DNA ladder formation. These findings present a proof that, within certain contexts, small-sized DNA fragmentation occurring in apoptosis may not necessarily be of the ladder yielding internucleosomal integer multiples' pattern. Our data also add to the evidence that the machinery underlying HMW DNA fragmentation is distinct from that responsible for the internucleosomal one.

Antimetabolites, Antineoplastic↗
PubMed2003

[Leiomyoma of spermatic cord: a case report].

A 68-year-old male was admitted to our hospital with the complaint of left painless mass of extratesticular scrotal content. Laboratory examinations were unremarkable. The tumor was resected by operation. The removed specimen was solid, 15 x 15 x 20 mm in size. Histopathological findings revealed leiomyoma. Other cases from the Japanese publications, together with our case, are reviewed.

Aged↗
PubMed2003

[A case of inverted papilloma of the prostatic urethra].

A 59-year-old male with a complaint of gross hematuria was found to have a pedunculated and non-papillary tumor on the prostatic urethra. The tumor was resected transurethrally. The pathological finding was inverted papilloma. Although the majority of the cases of inverted papilloma have been found in the bladder, we reported the 32nd case located on the prostatic urethra in Japan.

Humans↗