Search PubMed⌕ Search

Biomedical subjects

I Hara

Publications and source records attributed to I Hara.

At least 19 recordsLinked to original sources
PubMed2005

Aortic and vena caval reconstruction with retroperitoneal lymph node dissection for metastatic germ cell tumor.

A 49-year-old man who had a huge testicular tumor with retroperitoneal lymph node metastasis and bilateral multiple pulmonary metastases was referred to our hospital. Firstly orchiectomy was done obtaining the pathological diagnosis of mixed type germ cell tumor. After cisplatin-based chemotherapy, he underwent resection of the retroperitoneal lymph node involving the abdominal aorta and the inferior vena cava. Both great vessels were resected with the tumor and reconstructed with prosthetic grafts. Two months after the laparotomy, 12 metastatic nodules in the left lung were resected. Seven months later, he furthermore underwent resection of 4 metastatic nodules in the right lung. Microscopically, all resected metastatic tumors were diagnosed to be mature teratoma without viable malignant cells. The patient remains well 30 months after the first operation. Follow-up CT scan demonstrates patency of aortic and vena caval bypass grafts without local recurrence or distant metastasis.

Aorta↗
PubMed2004

Identification of parathyroid hormone-related protein-derived peptides immunogenic in human histocompatibility leukocyte antigen-A24+ prostate cancer patients.

Parathyroid hormone-related protein (PTHrP) is a key factor in the development of bone metastases, which are a major barrier in treating prostate cancer patients. In this study, we attempted to identify PTHrP-derived peptides immunogenic in human histocompatibility leukocyte antigen (HLA)-A24(+) prostate cancer patients. Among four different PTHrP peptides carrying the HLA-A24 binding motif, both the PTHrP(36-44) and PTHrP(102-111) peptides efficiently induced peptide-specific cytotoxic T lymphocytes from peripheral blood mononuclear cells (PBMCs) of HLA-A24(+) prostate cancer patients. Peptide-stimulated PBMCs showed cytotoxicity against prostate cancer cells in an HLA-A24-restricted manner. Experiments using antibodies and cold inhibition targets confirmed that their cytotoxicity was dependent on PTHrP peptide-specific and CD8(+) T cells. Immunoglobulin G reactive to the PTHrP(102-111) or PTHrP(110-119) peptide was frequently detected in the plasma of prostate cancer patients, suggesting that the PTHrP(102-111) peptide is able to elicit cellular and humoral immune responses in cancer patients. These results indicate that the PTHrP could be a promising target molecule for specific immunotherapy of HLA-A24(+) prostate cancer patients with metastases.

CD8-Positive T-Lymphocytes↗
PubMed2004

Significance of cancer detection in the anterior lateral horn on systematic prostate biopsy: the effect on pathological findings of radical prostatectomy specimens.

OBJECTIVE: To clarify the significance of cancer detection in the anterior lateral horn (ALH) on systematic prostate biopsy in relation to its effect on the pathological findings from retropubic radical prostatectomy (RRP) specimens. PATIENTS AND METHODS: The study included 84 consecutive patients who underwent RRP at our institution between January 1999 and December 2002, after being diagnosed as having prostate cancer, based on systematic prostate biopsies that included the areas taken by standard sextant biopsies and the bilateral ALHs. Several clinicopathological factors of these patients were analysed in relation to the presence or absence of cancer in the ALH on systematic biopsy. RESULTS: Of the 84 patients, cancer was detected in the ALH in 44 (group A), but not in the remaining 40 (group B). There were no significant differences in age, preoperative serum prostate-specific antigen level, or prostate volume between the groups. However, the incidence of bilateral positive cores and the percentage of positive biopsy cores in group A were significantly higher than those in group B. Pathological examinations of RRP specimens showed no significant differences in the incidence of lymphatic invasion, vascular invasion and perineural invasion, or Gleason score between the groups, but group A had a significantly larger tumour volume and higher incidence of extraprostatic disease than group B. CONCLUSIONS: Despite similar biological tumour characteristics and irrespective of the cancer location in the ALH, advanced and extensive disease frequently involves the ALH. Therefore, more aggressive treatment should be considered if cancer is detected in the ALH by systematic prostate biopsy.

Aged↗
PubMed2003

Swallowing and speech function after intraoral soft tissue reconstruction with lateral upper arm free flap and radial forearm free flap.

Swallowing, speech, and morbidity were assessed postoperatively in 25 patients, 18 of whom had had intraoral defects reconstructed by lateral upper arm free flaps (LUFF) and 7 by radial forearm free flaps (RFFF). Video fluoroscopy was used to assess swallowing, the Freiburger audiometric test to assess speech; and measurement of arm circumference to assess donor site morbidity. A questionnaire was used to evaluate swallowing, speech, and donor site morbidity subjectively. The degree of impairment in swallowing depended on the site of resection. Anterior and posterior resections affected swallowing more than lateral resections. Anterior resection and the use of LUFFs reduced intelligibility. There was no significant difference in impairment between LUFF and RFFF. We conclude that the LUFFs are superior to RFFFs because they can be closed primary and the incidence of donor site morbidity is slight.

Adult↗
PubMed2003

Increased urinary 8-hydroxy-2'-deoxyguanosine excretion after ileal neobladder replacement.

OBJECTIVES: To examine whether orthotopic neobladder replacement using either ileum or colon segments results in increased oxidative stress, by measuring urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG), one of the most commonly used markers for evaluating oxidative DNA damage. PATIENTS, SUBJECTS AND METHODS: Urinary levels of 8-OHdG and creatinine, urine analysis, nutritional status, and acid-base and electrolyte balances, were assessed in 22 patients with an ileal neobladder, 28 with a colon neobladder, 37 with an ileal conduit and 22 healthy volunteers. The results from both types of orthotopic neobladder, the ileal conduit and in the healthy controls were compared. RESULTS: The mean (sd) ratios of urinary 8-OHdG to urinary creatinine in patients with an ileal neobladder, colon neobladder, ileal conduit and in controls were 20.4 (7.8), 15.2 (4.3), 15.9 (5.1) and 15.2 (5.4) ng/mg, respectively. The urinary 8-OHdG ratio in the first group was significantly higher than in the other three groups. Among patients with a neobladder, the urinary 8-OHdG ratio was closely associated with the degree of pyuria, but not age, gender, the interval from surgery, body weight, height, serum creatinine or the degree of metabolic acidosis. CONCLUSIONS: These findings suggest that creating an ileal neobladder caused significantly greater oxidative stress than a colon neobladder, ileal conduit, or that in healthy controls. Therefore, it is recommended to conduct a careful long-term follow-up considering the possible development of malignant disease after urinary diversion, especially by an ileal neobladder.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2003

Evaluation of swallowing function after intraoral soft tissue reconstruction with microvascular free flaps.

This study assessed swallowing function after tumour resection and reconstruction utilizing free vascularized flap closures in patients with oral cancer. Swallowing function was evaluated postoperatively in 23 patients (21 men and 2 women) who had undergone reconstruction with either a lateral upper arm free flap (LUFF, n=16) or a radial forearm free flap (RFFF, n=7). Videofluoroscopy was used to assess tongue mobility and abnormalities of swallowing function. All patients who underwent reconstruction with LUFF or RFFF free flaps had decreased tongue mobility, except for the tip of the tongue. Patients who underwent anterior or posterior resection had greater decreases in tongue mobility than those who underwent medial resection. Swallowing impairment was similar in patients with LUFFs and those with RFFFs. Anterior resection of the oral cavity had a significant negative effect on swallowing function. Silent aspiration occurred in five patients. In conclusion the resection site affected swallowing function, but the type of flap did not, in patients with oral carcinoma, who underwent tumour resection with reconstruction

Adult↗
PubMed2002

Primary embryonal carcinoma of heart with SVC syndrome.

We present a case report of a 25-year-old man with embryonal carcinoma of right atrium and multiple lung metastases featuring SVC syndrome. We resected the cardiac tumor which occupied the right atrium and performed left upper lobectomy. No tumor mass or vestige was detected in the testes. Cis-platinum based combination chemotherapy was performed for residual lung tumors, which leads to the complete remission.

Adult↗
PubMed2002

Health-related quality of life after radical cystectomy for bladder cancer: a comparison of ileal conduit and orthotopic bladder replacement.

OBJECTIVE: To compare the health-related quality of life (HRQoL) after radical cystectomy in patients with an ileal conduit or an orthotopic neobladder. PATIENTS AND METHODS: The study included 85 men who underwent radical cystectomy for bladder cancer, comprising 48 with an orthotopic neobladder (26 with an ileal and 22 with a colon neobladder) and 37 with an ileal conduit. HRQoL was evaluated using the Short Form-36 survey containing 36 questions assessing eight aspects, including physical functioning, role-physical functioning, bodily pain, general health, vitality, social functioning, role-emotional functioning and mental health. RESULTS: The mean follow-up periods for patients with a neobladder (ileal and sigmoid) and with an ileal conduit was 45.9 (38.2 and 53.1, respectively) and 130.9 months, respectively. Scale scores were not affected by the duration of follow-up in either group. There was no significant difference in any scale scores between the neobladder and ileal conduit groups. However, general health and social functioning in both the neobladder and ileal conduit groups appeared to be significantly lower than those in the general population in the USA. Furthermore, patients with a colon neobladder had a significantly higher score for role-emotional functioning than those with an ileal neobladder, while there was no significant difference in the remaining seven scores between patients with ileal and colon neobladders. CONCLUSIONS: Six of the eight scales of HRQoL were favourable in both patients with a neobladder or an ileal conduit, and there was no significant difference between these groups. In addition, the HRQoL of patients with an orthotopic neobladder (except for role-emotional functioning) was unaffected by the segment of the intestine used for neobladder construction. Therefore, patients with both types of urinary diversion were generally satisfied with their overall health and quality of life.

Colon↗
PubMed2001

Simultaneous determination of six adenyl purines in human plasma by high-performance liquid chromatography with fluorescence derivatization.

A sensitive method was developed for the simultaneous determination of six adenyl purines in human plasma by high-performance liquid chromatography. The adenyl purines (adenine, adenosine, AMP, ADP, ATP and cyclic AMP) were derivatized using 2-chloroacetaldehyde for fluorescence detection, and the reaction and separation conditions were reinvestigated to improve sensitivity for small volume sample analysis. Each derivatized purine was separated on a Capcell Pack SG120A column with mobile phase consisting of 0.05 M citric acid-0.1 M dipotassium hydrogen phosphate (pH 4.0)-methanol (97+3). The detection limits were 100-1000 fmol/ml by fluorescence detection, some 500 times better than previous reports. The proposed method was applied to determine adenyl purines in human plasma. The purine levels were as follows: ATP (9.2-22.2 pmol/ml), ADP (5.5-22.2 pmol/ml), AMP (0.8-3.2 pmol/ml). Other purines, adenine, adenosine, cAMP were lower than 0.1 pmol/ml.

Calibration↗
PubMed2001

Oxidative modification of tryptophan 43 in the heme vicinity of the F43W/H64L myoglobin mutant.

The F43W/H64L myoglobin mutant was previously constructed to investigate the effects of electron-rich tryptophan residue in the heme vicinity on the catalysis, where we found that Trp-43 in the mutant was oxidatively modified in the reaction with m-chloroperbenzoic acid (mCPBA). To identify the exact structure of the modified tryptophan in this study, the mCPBA-treated F43W/H64L mutant has been digested stepwise with Lys-C achromobacter and trypsin to isolate two oxidation products by preparative fast protein liquid chromatography. The close examinations of the (1)H NMR spectra of peptide fragments reveal that two forms of the modified tryptophan must have 2,6-disubstituted indole substructures. The (13)C NMR analysis suggests that one of the modified tryptophan bears a unique hydroxyl group in stead of the NH(2) group at the amino-terminal. The results together with mass spectrometry (MS)/MS analysis (30 Da increase in mass of Trp-43) indicate that oxidation products of Trp-43 are 2,6-dihydro-2,6-dioxoindole and 2,6-dihydro-2-imino-6-oxoindole derivatives. Our finding is the first example of the oxidation of aromatic carbons by the myoglobin mutant system.

Catalysis↗
PubMed2001

Overexpression of Bcl-2 regulates sodium butyrate- and/or docetaxel-induced apoptosis in human bladder cancer cells both in vitro and in vivo.

Sodium butyrate (NaBt), a physiologically occurring short-chain fatty acid, induces differentiation as well as apoptosis in numerous cell types, and this induction is partially regulated by Bcl-2 expression. The objectives of our study were to characterize the in vitro effects of NaBt and/or docetaxel on the growth, cell cycle and apoptosis of human bladder cancer cells, and to determine whether tumor growth in vivo is inhibited by isobutyramide, an orally bioavailable Bt analogue, and/or docetaxel by using Bcl-2-transfected human bladder cancer cell line KoTCC-1/BH and control vector only-transfected cell line KoTCC-1/C. NaBt caused a decrease in growth of both KoTCC-1/C and KoTCC-1/BH cells, however, its growth inhibitory effect was significantly greater in KoTCC-1/C cells. One mM NaBt resulted in G1 cell cycle arrest, accompanied by up-regulation of p21 (waf1/cip1) and down-regulation of cyclin D1 in KoTCC-1/C cells, whereas KoTCC-1/BH showed resistance to G1 cell cycle arrest. An amount of 5 mM NaBt induced apoptosis, accompanied by up-regulation of Bak in KoTCC-1/C cells but failed to induce apoptosis in KoTCC-1/BH cells despite substantial down-regulation of Bcl-2. Oral administration of isobutyramide significantly reduced the KoTCC-1/C tumor volume compared with the KoTCC-1/BH tumor volume in nude mice. Furthermore, docetaxel induced Bcl-2 phosphorylation in KoTCC-1/BH cells and combined treatment with isobutyramide and docetaxel synergistically inhibited the growth of KoTCC-1/BH cells both in vitro and in vivo. These findings suggest that isobutyramide therapy could be a novel therapeutic strategy for patients with bladder cancer if docetaxel is combined according to the Bcl-2 expression status.

Amides↗
PubMed2001

Optimal timing and dosage of chemotherapy as a combined treatment with androgen withdrawal in the human prostate LNCaP tumour model.

Although numerous chemotherapeutic agents have been evaluated for patients with advanced prostate cancer, none have demonstrated improved survival benefits. Here, in order to determine whether the efficacy of chemotherapy can be enhanced by changing the regimen, we evaluated the effect of the varied timing and dosage of chemotherapy in combination with androgen withdrawal on time to androgen-independent (AI) progression in the human androgen-dependent LNCaP tumour model. We first demonstrated the synergistic effect of mitoxantrone on induction of apoptosis in LNCaP cells maintained in the steroid hormone-depleted charcoal-stripped media (CSM) compared to those in the standard media. In addition, this synergy was most remarkable during the simultaneous treatment of LNCaP cells with mitoxantrone and CSM compared to the pre- or post-use of mitoxantrone with CSM. LNCaP tumour growth in athymic nude mice and their increase in serum PSA levels were significantly inhibited by the simultaneous injection of mitoxantrone with castration, compared to the administration of mitoxantrone 2 weeks before or after castration. The TUNEL staining revealed that apoptotic cell death was extensively induced in LNCaP tumours treated with simultaneous castration and mitoxantrone compared to tumours treated with the other schedules. Furthermore, nude mice bearing LNCaP tumours were injected with a total of 0.5 mg mitoxantrone divided into 2, 5 and 10 days, with the most significant therapeutic effect and delayed AI progression observed in mice given injection of mitoxantrone for 2 days. These findings suggest that this might be the optimal way to perform cytotoxic chemotherapy and androgen withdrawal simultaneously in patients with advanced prostate cancer and to administer chemotherapeutic agents at high dosage within short intervals.

Androgens↗
PubMed2001

Molecular engineering of myoglobin: the improvement of oxidation activity by replacing Phe-43 with tryptophan.

The F43W and F43W/H64L myoglobin (Mb) mutants have been constructed to investigate effects of an electron rich oxidizable amino acid residue in the heme vicinity on oxidation activities of Mb. The Phe-43 --> Trp mutation increases the rate of one-electron oxidation of guaiacol by 3-4-fold; however, the peroxidase activity for F43W/H64L Mb is less than that of the F43W single mutant because the absence of histidine, a general acid-base catalyst, in the distal heme pocket suppresses compound I formation. More than 15-fold improvement versus wild-type Mb in the two-electron oxidation of thioanisole and styrene is observed with the Phe-43 --> Trp mutation. Our results indicate that Trp-43 in the mutants enhances both one- and two-electron oxidation activities (i.e., F43W Mb > wild-type Mb and F43W/H64L Mb > H64L Mb). The level of (18)O incorporation from H2(18)O2 into the epoxide product for the wild type is 31%; however, the values for F43W and F43W/H64L Mb are 75 and 73%, respectively. Thus, Trp-43 in the mutants does not appear to be utilized as a major protein radical site to form a peroxy protein radical in the oxygenation. The enhanced peroxygenase activity might be explained by the increase in the reactivity of compound I. However, the oxidative modification of F43W/H64L Mb in compound I formation with mCPBA prevents us from determining the actual reactivity of the catalytic species for the intact protein. The Lys-C achromobacter digestion of the modified F43W/H64L mutant followed by FPLC and mass analysis shows that the Trp-43-Lys-47 fragment gains a mass by 30 Da, which could correspond two oxygen atoms and loss of two protons.

Amino Acid Substitution↗
PubMed2001

Synergistic antitumor effect of ionomycin and cisplatin against renal cell carcinoma in vitro and in vivo.

Objectives. To characterize the synergistic antitumor effects of the calcium ionophore, ionomycin, and of cisplatin against human renal cell carcinoma cell line, ACHN, both in vitro and in vivo.Methods. The in vitro growth rate of ACHN after exposure to these compounds was measured, using the MTT assay. The apoptotic features in ACHN were evaluated by DNA ladder analysis and flow cytometric analysis. Bcl-2 and Bax expression levels in ACHN after treatment were examined by Western blot. The synergistic antitumor effects of ionomycin and cisplatin against the growth of established ACHN tumors in athymic nude mice were then tested.Results. The in vitro growth rate of ACHN was suppressed more by ionomycin and cisplatin in combination than by either alone. DNA ladder and fragmentation were more obvious when the cells were incubated with ionomycin and cisplatin together than with either reagent alone. Ionomycin treatment increased the expression level of Bax protein, whereas Bcl-2 expression was not influenced. Although an intraperitoneal injection of cisplatin or an intratumoral injection of ionomycin against subcutaneous ACHN tumors somewhat reduced tumorigenicity in nude mice, the effect was significantly enhanced by a combination of these drugs.Conclusions. The synergistic antitumor effects suggest that ionomycin-based therapy could be a novel therapeutic strategy with which to treat advanced renal cell carcinoma.

Animals↗
PubMed2001

Increased Fas ligand expression in the tumor tissue and serum of patients with testicular germ cell tumors with seminomatous elements.

OBJECTIVES: To measure the expression levels of Fas and Fas ligand (FasL) in testicular germ cell tumor (TGCT) and to determine whether the serum level of soluble FasL (sFasL) could be used as a marker for patients with TGCT. METHODS: The expression of Fas and FasL in 51 specimens obtained from patients with TGCT was examined by reverse transcriptase-polymerase chain reaction, and the results were confirmed by Western blot analysis. The serum levels of sFasL in 24 patients with TGCT were measured using an enzyme-linked immunosorbent assay system. RESULTS: Of 33 TGCT specimens that included seminomatous elements, Fas and FasL was expressed in 24 (73%) and 24 (73%), respectively. On the other hand, 10 (56%) and 2 (11%) specimens expressed Fas and FasL, respectively, in 18 TGCT specimens without seminomatous elements. Moreover, the serum levels of sFasL were significantly higher in patients with TGCT with a seminomatous element than in those without it. CONCLUSIONS: These results indicate that FasL is strongly expressed in tumor tissue and is present at high levels in the serum of patients with TGCT with a seminomatous element compared with those without it and that the serum levels of sFasL could be used as a novel diagnostic marker for TGCT with seminomatous elements.

Biomarkers, Tumor↗
PubMed2001

Novel therapeutic strategy for advanced prostate cancer using antisense oligodeoxynucleotides targeting anti-apoptotic genes upregulated after androgen withdrawal to delay androgen-independent progression and enhance chemosensitivity.

Progression to androgen-independence remains the main obstacle to improving survival for patients with advanced prostate cancer. In this review, findings are summarized that have recently been demonstrated to establish novel therapeutic strategy targeting several genes playing functionally important roles after androgen withdrawal and during androgen-independent progression. The authors initially characterized changes in gene expression after androgen withdrawal in the androgen-dependent Shionogi and LNCaP tumor models using cDNA arrays. Based on these results, they focused on genes highly upregulated after androgen ablation (i.e. bcl-2, bcl-xL, TR.PM-2, IGFBP-5), which have anti-apoptotic or mitogenic activities, and thereby confer a resistance to androgen withdrawal as well as cytotoxic chemotherapy. The authors further demonstrated the efficacy of an antisense oligodeoxynucleotide (ODN) strategy for patients with advanced prostate cancer through the inhibition of target gene expression, resulting in a delay in the progression to androgen-independence by enhancing apoptotic cell death induced by androgen ablation and chemotherapy. The authors also showed the effectiveness of combined antisense ODN therapy and cytotoxic chemotherapy by achieving additive or synergistic effects. These findings provide a basic significance for the design of clinical studies using antisense ODN either alone or in combination with chemotherapeutic agents in patients with advanced prostate cancer.

Androgens↗
PubMed2001

Value of prostate specific antigen alpha1-antichymotrypsin complex for the detection of prostate cancer in patients with a PSA level of 4.1-10.0 ng/mL: comparison with PSA-related parameters.

BACKGROUND: The aim of the present study was to evaluate the usefulness of prostate specific antigen alpha1-antichymotrypsin complex (PSA-ACT) in the differential diagnosis of prostate cancer in patients with a PSA level of 4.1-10.0 ng/mL compared to several PSA- and PSA-ACT-related parameters. METHODS: Serum samples were obtained from 103 patients with no evidence of malignancy on biopsy and 29 with histologically confirmed prostate cancer. All patients had pretreatment serum PSA levels between 4.0 and 10.0 ng/mL. The different forms of serum PSA, including total PSA (tPSA), free PSA (fPSA) and PSA-ACT were measured using immunofluorometric techniques with different monoclonal antibodies against PSA and ACT. Furthermore, tPSA and PSA-ACT densities of the whole prostate (PSAD and ACTD, respectively) and the f-to-tPSA and the f-to-PSA-ACT ratios (F/T ratio and F/ACT ratio, respectively) were calculated. RESULTS: The differences between patients with prostate cancer and benign prostatic disease were significant with respect to all six parameters examined in this study. Analysis of receiver operating characteristics revealed that the areas under the curve for PSA-ACT, ACTD and the F/ACT ratio were larger than those for tPSA, PSAD and the F/T ratio, respectively. However, there were no significant differences in discrimination between benign and malignant diseases among these six parameters. CONCLUSIONS: In patients who have an intermediate serum PSA level, PSA-ACT and its associated parameters may not be significantly superior in the differential diagnosis between prostate cancer and benign prostatic diseases compared to tPSA and its traditional relatives.

Aged↗