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Biomedical subjects

Hiroshi Hoshiai

Publications and source records attributed to Hiroshi Hoshiai.

At least 19 recordsLinked to original sources
PubMed2007

Hypoxia inducible factor 1-alpha expression as a factor predictive of efficacy of taxane/platinum chemotherapy in advanced primary epithelial ovarian cancer.

To investigate the impact on survival of HIF 1-alpha expression on primary advanced epithelial ovarian cancer (EOC), we examined the correlations between prognosis and HIF 1-alpha expression by Western blot analysis in 52 cases of stage III/IV EOC. HIF 1-alpha expression was confirmed in 36 cases (69.2%) of EOC, and HIF 1-alpha-expressing tumors had a significantly higher rate of response (p<0.01) to postoperative paclitaxel/carboplatin combination chemotherapy (TC) than tumors without HIF1-alpha expression. Moreover, patients with HIF 1-alpha-expressing tumors with suboptimal resection of stage III/IV tumors indicated for postoperative TC exhibited significantly better survival (p<0.01).

Adult↗
PubMed2006

IgG antibodies to HPV16, 52, 58 and 6 L1-capsids and spontaneous regression of cervical intraepithelial neoplasia.

To identify the predictive markers for spontaneous regression of cervical intraepithelial neoplasia (CIN), we examined whether IgG antibody responses to common human papillomavirus (HPV) L1-capsids correlate with CIN regression. In a cohort study, a total of 116 Japanese women with CIN grade I/II were tested for cervical HPV DNA and serum IgG antibodies to HPV16/52/58/6 L1-capsids. Our data suggest that baseline IgG reactivities to HPV L1-capsids do not serve as a predictive marker of CIN regression, in contrast to histological CIN grades and HPV DNA status.

Antibodies, Viral↗
PubMed2006

Feasibility of concurrent cisplatin use during primary and adjuvant chemoradiation therapy: a phase I study in Japanese patients with cancer of the uterine cervix.

BACKGROUND: Although the prognostic advantages of concurrent cisplatin (CDDP) chemoradiation therapy (CCRT), for uterine cervical cancer (UCC) has been demonstrated, the feasibility of concurrent CDDP administration has not yet been evaluated. We determined the optimal CDDP dose for both weekly and monthly schedules during primary and adjuvant CCRT in patients with UCC. METHODS: The study was conducted as a phase I, dose-escalation trial. Concurrent CDDP was started at the dose of 30 mg/m(2) for the weekly schedule and at 50 mg/m(2) for the monthly schedule, and the doses were steadily escalated to the maximum tolerated dose (MTD). RESULTS: A total of 45 patients with UCC (25 receiving primary CCRT and 20 receiving adjuvant CCRT) were entered in the study. In both the primary and adjuvant CCRT patients, the MTD was observed to be 40 mg/m(2) for the weekly schedule and 80 mg/m(2) for the monthly schedule. Dose-limiting toxicity was observed in 10 patients (granulocytopenia in 9 patients and diarrhea in 1 patient). Disease recurrence was confirmed in 6 patients in the primary CCRT group during a mean follow-up period of 22.4 +/- 13.2 months, and in patients 3 in the adjuvant CCRT group during a mean follow-up period of 17.7 +/- 6.8 months. CONCLUSION: For Japanese patients with UCC receiving primary or adjuvant CCRT therapy, the recommended CDDP dose was determined to be 30 mg/m(2) for the weekly schedule and 75 mg/m(2) for the monthly schedule.

Adult↗
PubMed2006

Preoperative diagnosis of ovarian tumors, focusing on the solid area based on diagnostic imaging.

AIM: The objectives were to attempt to differentiate between benignancy and malignancy by focusing not on macroscopic finding of tumor sections, but on the solid areas by diagnostic imaging. To investigate the usefulness of diagnostic imaging for ovarian tumors, we examined the solid areas in the tumor and their shape and analyzed the relationship between these factors and the malignant potential. METHODS: Subjects were 921 surgical cases (1074 tumors) over a period of 7 years. Diagnostic images (ultrasonography, computed tomography and magnetic resonance imaging) were reread, focusing on the solid area. Tumors were classified into four groups according to the prominence of the solid area, and the findings were compared with the postoperative diagnosis. RESULTS: Of the cases, 718 indicated benign, borderline malignancy in 29 and malignancy in 174. The malignant potential of tumors with solid areas was significantly higher than those with no solid area. However, upon comparison among the different groups with solid areas, no significant differences were detected in terms of the frequency at which malignancies were detected, despite the differences between the groups with respect to size and shape. CONCLUSION: It is important for the treatment strategy that solid areas, even if small, should not be neglected, and that malignancies are found at high frequency regardless of shape, size and prominence.

Adolescent↗
PubMed2006

Inhibition of Oct4 expression in mouse preimplantation embryos using morpholino antisense oligonucleotides.

Morpholino oligonucleotides (MO) can induce gene silencing by binding to a target mRNA and inhibiting its translation, and this technique has been especially successful in studies of embryonic development in various vertebrates. But in mice MO-induced downregulation of target genes has not been widely reported. In this study, we examined whether MO delivery using ethoxylated polyethylenimine (EPEI) delivery reagent is useful for silencing gene expression in the mouse preimplantation embryo, by targeting endogenous gene Oct4. To optimize the conditions for MO delivery, we examined the MO concentration, the EPEI concentration, the treatment time, and the number of MO treatments. The MO treatment was performed at the 2-cell, the morula, the blastocyst, and the hatched blastocyst stage. We first determined the optimal conditions for MO delivery into the nucleus using fluorescein isothiocyanate (FITC)-labeled MO, and demonstrated that treatment with a combination of 20 microM MO and 0.56 microM EPEI for 3 hrs produced effective MO delivery. MO-induced downregulation of Oct4 was then examined. Two-step MO treatment at the 2-cell and blastocyst stages successfully suppressed Oct4 expression. This MO treatment resulted in marked reduction of Oct4 protein at the blastocyst stage. After cultivation of blastocysts for further 4 days, derivatives of embryos either differentiated to trophoblastic cells or showed developmental arrest at the blastocyst. This phenocopy is similar to Oct4-deficient embryos. Overall, our results indicate that MO delivery with EPEI is an effective tool for analyzing gene function in mouse preimplantation embryos.

Animals↗
PubMed2005

Evaluation of weekly low-dose paclitaxel and carboplatin treatment for patients with platinum-sensitive relapsed ovarian cancer.

OBJECTIVE: Although paclitaxel and carboplatin therapy (TC) is an established effective standard regimen for patients with ovarian cancer, both treatment delay for hematologic toxicity and discontinuation of treatment due to neurotoxicity have occasionally been reported. To achieve therapeutic density, we evaluated the usefulness of weekly low-dose TC therapy (WTC) in patients with platinum-sensitive (median PFI was 11.4 +/- 2.7 months) recurrent epithelial ovarian cancer. METHODS: A total of 25 patients were treated with paclitaxel at 60 mg/m(2) and carboplatin at AUC = 2 using 3 weekly courses with a 1-week break schedule. Eighteen patients had assessable tumors for response, and the other seven patients were evaluated by CA-125-based response. All of the patients were assessable for toxicity. RESULTS: The overall response rate (OR) based on WHO criteria was 84.2% (95% CI; 0.65-0.98), including nine complete responses (CR); OR based on CA-125 was 85.7% (95% CI; 0.42-0.99), including 3 CR. The total response rate was 88.0% (95% C.I.; 0.68-0.97). The median progression-free survival of the patients was 13.5 months during the mean follow-up period of 21.9 +/- 9.2 months. No patients had grade 1 or higher thrombocytopenia, and although 44% of the patients developed neurotoxicity, all cases remained grade 1. Treatment delay of over 7 days due to toxicity was observed in only two patients (16.0%) and in six cycles (1.3%) in a total of 451 cycles. CONCLUSION: WTC combination, as used in this study, produced a high response rate with acceptable toxicity, and the optimal combination in a weekly regimen remains to be determined.

Adult↗
PubMed2005

The effect of granisetron on in vitro metabolism of doxorubicin, irinotecan and etoposide.

OBJECTIVE: Doxorubicin, irinotecan and etoposide are all associated with the debilitating side-effects of nausea and vomiting, thereby necessitating concomitant antiemetic therapy. However, this may increase the potential for drug-drug interactions by inhibition or induction of the cytochrome P450 enzymes. A study was undertaken to investigate the effects of the 5-HT(3) -receptor antagonist granisetron on the metabolism of doxorubicin, irinotecan and etoposide in vitro in human liver microsomal preparations. RESEARCH DESIGN AND METHODS: Doxorubicin, 20 microM, irinotecan, 10 microM, and etoposide, 50 microM, were incubated in the presence of granisetron, 0 nM, 20 nM, 200 nM and 2000 nM, in human liver microsomal preparations (250 microg). The levels of unchanged doxorubicin, irinotecan and etoposide in the incubation mixture were determined by high-performance liquid chromatography. Positive controls were ketoconazole, 20 microM, a potent inhibitor of CYP3A metabolism, for irinotecan and etoposide and quercitrin, 2 mM, a potent inhibitor of aldo-keto reductase, for doxorubicin. RESULTS: In the absence of granisetron, unchanged doxorubicin, irinotecan and etoposide levels decreased by 34.2 +/- 5.5%, 21.3 +/- 2.9% and 13.4 +/- 1.6% of control, respectively. Ketoconazole prevented the breakdown of both irinotecan and etoposide, while quercitrin inhibited the breakdown of doxorubicin. Granisetron had no effect on the rate of reduction of doxorubicin, irinotecan or etoposide. CONCLUSIONS: The results from this study suggest that granisetron neither inhibits nor induces the enzymes involved in the metabolism of doxorubicin, irinotecan or etoposide. Thus, granisetron can be used safely to treat nausea and vomiting induced by these agents with minimal risk of drug-drug interactions.

Antibiotics, Antineoplastic↗
PubMed2005

Current guidelines for treatment of endometriosis. The present status in Japan.

Laparoscopy currently remains the only effective tool for the diagnosis and evaluation of endometriosis, and in Japan is particularly recommended in patients with concurrent infertility. Diagnosis based on clinical examination alone is associated with a false-negative rate of 19% and a false-positive rate of 44%. Furthermore, unidentified and untreated endometriosis progresses 0.3 revised American Fertility Society (Re-AFS) stage points per month. Given this gradual progression, medical therapy, including long-term treatment, should be initiated in women with definitive evidence of endometriosis who need to maintain their reproductive potential. Gonadotropin- releasing hormone (GnRH) agonists are recommended for the treatment of endometriosis-associated pelvic pain in younger women who wish to become pregnant at a later date, and in women in whom reproductive status is not a concern. Laparoscopy should be used in patients with endometriosis and infertility, while GnRH agonists should be used in patients with pelvic pain.

Endometriosis↗
PubMed2003

Platelet-derived endothelial cell growth factor predicts of progression and recurrence in primary epithelial ovarian cancer.

We investigated the clinical significance of platelet-derived endothelial cell growth factor (PD-ECGF) as measured by enzyme-linked immunosorbent assay in primary epithelial ovarian cancers (EOC), finding amounts to be significantly greater in cancers than in normal ovarian tissue (p<0.01). PD-ECGF was significantly more abundant in stages III and IV than in lower stages (p<0.05), and also was high in tumors with macroscopically evident metastases in the peritoneal cavity (p<0.05), or pelvic (p<0.01) or paraaortic (p<0.01) lymph node metastases. Further, PD-ECGF was significantly lower in mucinous than in serous adenocarcinomas (p<0.05). No significant correlation was seen between PD-ECGF and histologic grade, maximum intraperitoneal metastatic tumor diameter (<2 vs.>2 cm), or presence of demonstrable malignant cells in peritoneal fluid. In stage III disease, PD-ECGF exhibited significant correlation with recurrence (p<0.05). Our data suggested that results of PD-ECGF assays in primary tumors can predict progression and recurrence of EOC.

Adult↗
PubMed2003

Prognostic factors associated with the clinical outcome of cervical intraepithelial neoplasia: a cohort study in Japan.

One hundred and eighty-five Japanese women with cervical intraepithelial neoplasia (CIN) were enrolled in this follow-up study. On the basis of the prevalence of human papillomavirus (HPV) DNA in Japanese cervical cancer patients, HPV types were categorized into three groups as follows: (1) high risk (types 16, 18, 33, 52, and 58), (2) intermediate risk (types 31, 35, 39, 51, 56, 59, 68, and 70), (3) low risk (type 6, 30, 42, 53, 54, 55, 66 and unclassified types). High-risk HPV infection was a risk factor for progression of the disease. The regression rate in the HPV negative group was higher (83.3%) than those in the HPV positive groups, but the differences in regression were no longer significant after adjustment for age and CIN grade. It is also noted that a lower cytomegalovirus IgG level and a smaller number of past pregnancies might be associated with the regression of CIN lesions.

Cohort Studies↗
PubMed2002

Is endometriosis really associated with pain?

To address the contrasting findings regarding how pain is related to endometriosis, the relationship between pain and stage of endometriosis was dissected differently by the chief complaint to eliminate selection biases. A total of 1,092 women with endometriosis were classified into two groups depending on their chief complaint, i.e., infertility (infertility group; n = 476) or pain (pain group; n = 616). The correlations between disease stage and various types of pain were analyzed differently in each group. The frequencies of chronic pelvic pain and dyspareunia increased with disease stage either in the infertility group, in the pain group or in the aggregate. On the other hand, no significant relation between the severity of dysmenorrhea and disease stage was observed in the aggregate. Interestingly, a parallel increase in the severity of dysmenorrhea with disease stage was observed in the infertility group, but not in the pain group. In view of selection biases involved in analyzing endometriosis associated with pain, these results could be seen to support the contention that chronic pelvic pain, dyspareunia and dysmenorrhea are in fact related to the extent of endometriosis.

Adolescent↗
PubMedDate not supplied

The effect of granisetron on in vitro metabolism of paclitaxel and docetaxel.

PURPOSE: Paclitaxel and docetaxel are effective anticancer agents; however, these agents can be associated with the debilitating side effects of nausea and vomiting, thereby necessitatingthe administration of concomitant antiemetic agents. This increases the potential fordrug-drug interactionsthrough inhibition or induction of the cytochrome P450 (CYP) enzymes. The 5-HT3-receptor antagonists are currently regarded as the antiemetic 'gold standard' and this study was undertaken to investigate the effects of granisetron on the metabolism of paclitaxel and docetaxel in human liver microsomal preparations in vitro. METHODS: Paclitaxel, 5 nM, and docetaxel, 1.25 nM, were incubated in the presence of granisetron, 0, 10, 100, and 1000 pM, in human liver microsomal preparations (500 microg). The levels of unchanged paclitaxel and docetaxel in the incubation mixture were determined by high-performance liquid chromatography. Ketoconazole, 10 nM, a potent inhibitor of CYP3A metabolism, served as a positive control. RESULTS: In the absence of granisetron, unchanged paclitaxel and docetaxel levels measured were 27.2 +/- 2.8% and 44.3 +/- 4.0% of control, respectively. Ketoconazole prevented the breakdown of both paclitaxel and docetaxel, to the degree that no unchanged paclitaxel or docetaxel was detected in the incubation mixture. Granisetron had no effect on the rate of reduction of either paclitaxel or docetaxel; unchanged paclitaxel and docetaxel decreased to 25.0 +/- 1.5%, 26.4 +/- 1.0%, and 27.6 +/- 6.4%, and 44.2 +/- 1.5%, 41.2 +/- 4.1%, and 43.1 +/- 0.5%, respectively. DISCUSSION: The results from this study suggest that granisetron neither inhibits nor induces the enzymes involved in the metabolism of paclitaxel or docetaxel. Thus, granisetron can be used safely as a supportive care agent to treat paclitaxel or docetaxel chemotherapy-induced nausea and vomiting with minimal risk of drug-drug interactions.

Analysis of Variance↗
PubMedDate not supplied

Cytopathologic and clinicopathologic features of ovarian hepatoid carcinoma. A case report.

BACKGROUND: Hepatoid carcinoma is a rare ovarian tumor and is thought to be a different histopathologic subtype from hepatoid-type yolk sac tumor based upon its pathologic features. However, the cytopathologic characteristics of ovarian hepatoid carcinoma (OHC) have not been reported previously. We report the clinicopathologic and cytopathologic features and immunoreactivity of a case of OHC. CASE: A 36-year-old woman presented to our department with lower abdominal pain. A left ovarian tumor was found on pelvic examination, magnetic resonance imaging and computed tomography. The tumor was diagnosed as a hepatoid carcinoma of the left ovary based upon the histopathology of the surgically resected specimen. Cytopathologic specimens from a tumor touch preparation of the tumor exhibited pleomorphic tumor cells with abundant cytoplasm. The nuclei contained rough, granular chromatin and large, prominent nucleoli. Several tumor cells were multinucleated. Tumor cells were immunoreactive for alpha-fetoprotein (AFP). Hematoxylin and eosin staining revealed that the tumor cells were in a sinusoidal pattern resembling hepatocellular carcinoma without any glandular formation. The tumor cells were negative for human chorionic gonadotropin while positive for AFP, alpha-1-antitripsin, CA-125 and carcinoembryonic antigen. CONCLUSION: Cytopathologic examination is of considerable aid in the diagnosis of OHC since cytopathologic preparations highlight the characteristic cell pleomorphism.

Adult↗
PubMedDate not supplied

Advanced primary clear cell carcinoma of the vagina not associated with diethylstilbestrol.

BACKGROUND: Primary vaginal clear cell carcinoma occurs in young women exposed to diethylstilbestrol (DES) in utero. Primary vaginal clear cell carcinoma not associated with DES is very rare. We report the clinicopathologic and cytopathologic features of a patient with advanced, sporadic primary vaginal clear cell carcinoma with metastases to liver, lung and paraaortic lymph nodes. CASE: A postmenopausal, 63-year-old woman presented to our department with genital bleeding. A hemorrhagic tumor found in the vagina was diagnosed as a clear cell carcinoma by cytopathologic examination of the tumor smear and by histopathologic examination of a biopsy specimen. A chest radiograph revealed multiple lung metastases, and metastases to the liver and paraaortic lymph nodes were noted on computed tomography and magnetic resonance imaging. The tumor was diagnosed as primary clear cell carcinoma of the vagina, stage IVb (FIGO) based on a normal cytopathologic examination of the cervix, endometrium and ascites; normal appearance of the uterus, ovaries and kidneys on magnetic resonance imaging; and absence of detectable tumor in the urinary tract. The patient died of respiratory failure 31 days after hospitalization. The tumor demonstrated overexpression of p53 protein and did not show microsatellite instability. CONCLUSION: This patient was the second reported Japanese woman with advanced primary vaginal clear cell carcinoma not associated with DES.

Adenocarcinoma, Clear Cell↗
PubMedDate not supplied

Antitumor activity of new combination chemotherapy with irinotecan hydrochloride and nedaplatin against human cervical cancer cell lines.

Antitumor activity of combination chemotherapy with irinotecan hydrochloride (CPT-11) and nedaplatin was compared to that with CPT-11 and cisplatin. In vitro cytotoxicity of SN-38 (an active metabolite of CPT-11) in combination with nedaplatin or cisplatin was evaluated using three human cervical cancer cell lines (ME-180, CaSki and SiHa). IC50 values of nedaplatin against these three human cervical cancer cell lines were about 2-fold as high as those of cisplatin, indicating somewhat weak cytotoxic effects of nedaplatin. Interactions between two drugs in combination were investigated using a simultaneous-exposure schedule and analyzed by the IC50-based isobologram method. Simultaneous exposure to SN-38 with each platinum preparation showed synergistic and additive effects against ME-180 and SiHa. In vivo antitumor effects of CPT-11 in the combination with each platinum were studied using SiHa xenografts. While CPT-11, nedaplatin and cisplatin alone hardly showed any antitumor effects even at the maximum tolerated dose (MTD) levels, the combination chemotherapy with CPT-11 and nedaplatin or cisplatin resulted in significant antitumor effects even at three-quarter MTD of CPT-11 combined with two-third MTD of platinum. All treatments were tolerable for mice, indicating that the combinations did not cause significant enhancement in toxicity. In clinical application, nedaplatin causes a lower incidence of nephropathy and does not require the replacement of a large volume of fluid, which is needed for cisplatin administration, facilitating treatment at the out-patient clinic. In addition, the incidences of digestive disorder, peripheral neuropathy and auditory disorder are lower. These findings suggest that the combination chemotherapy with CPT-11 and nedaplatin for squamous cell cancer of uterine cervix is very useful in clinical practice. A dose-finding study should be conducted.

Animals↗