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Toshiharu Kamura

Publications and source records attributed to Toshiharu Kamura.

At least 19 recordsLinked to original sources
PubMed2006

Fertility-preserving treatment for patients with malignant germ cell tumors of the ovary.

AIM: The aim of this study was to investigate whether fertility preservation influences the clinical outcome in patients with malignant germ cell tumors of the ovary (MGCTO). METHODS: A case study analysis was performed on patients with MGCTO treated at Kurume University Hospital between 1986 and 2004. Thirty-five patients were included in the study, 14 with immature teratoma, 11 with dysgerminoma, eight with endodermal sinus tumor, and two with mixed germ cell tumor. Twenty-three patients had International Federation of Gynecology and Obstetrics stage I (Ia, 11; Ib, 2; Ic, 10), one had stage II, seven had stage III, and four had stage IV disease. RESULTS: Five patients with stage III or IV disease received radical surgery. Thirty patients underwent conservative surgery. As the adjuvant treatment, 30 patients received chemotherapy, while five patients did not receive any chemotherapy. The overall survival rate was 97.1%. One patient died of the disease. She was 13 years old with a stage IV endodermal sinus tumor. Twelve have attempted conception, and eight have achieved at least one pregnancy (66.7%). CONCLUSIONS: Irrespective of the stage of the disease, conservative surgery and adjuvant chemotherapy for MGCTO can achieve a favorable outcome in terms of survival and fertility.

Adolescent↗
PubMed2005

Identification of human papillomavirus 16-E6 protein-derived peptides with the potential to generate cytotoxic T-lymphocytes toward human leukocyte antigen-A24+ cervical cancer.

Human papillomavirus 16 (HPV16)-E6 and -E7 proteins are considered to be appropriate targets in specific immunotherapy for cervical cancer. In this study, we attempted to identify epitope peptides from the HPV16-E6 protein that have the potential to generate cytotoxic T-lymphocytes (CTLs) toward human leukocyte antigen (HLA)-A24+ cervical cancer. Two HPV16-E6 peptides at positions 75-83 and 91-100 effectively induced peptide-specific CTLs from peripheral blood mononuclear cells of HLA-A24+ cervical cancer patients. These HPV16-E6 peptide-induced CTLs showed cytotoxicity against HLA-A24+ and HPV16-E6 protein-expressing cervical cancer cells. Experiments with blocking antibodies and cold inhibition targets revealed that the cytotoxicity was mainly dependent on peptide-specific and CD8+ T cells. In addition, based on our observation that induction of immunoglobulin G (IgG) reactive to administered CTL-directed peptides is correlated with clinical responses, we attempted to detect IgG reactive to HPV16-E6 peptides in the plasma of cancer patients. As a result, IgGs reactive to the HPV16-E691-100 peptide were detected in 4 of 12 cervical cancer patients. These results indicate that these HPV16-E6-derived peptides are good candidates in peptide-based immunotherapy for HLA-A24+ cervical cancer patients.

Female↗
PubMed2004

Antiproliferative effects of interferon-alphaCon1 on ovarian clear cell adenocarcinoma in vitro and in vivo.

PURPOSE: We examined the antiproliferative effect of IFN-alphaCon1 and its mechanism on ovarian clear cell adenocarcinoma in vitro and in vivo. EXPERIMENTAL DESIGN: (a) The effects of IFN-alphaCon1 on growth, morphology, cell cycle, and type I IFN-alpha receptor (IFNAR-2) expression were examined on two ovarian clear cell adenocarcinoma cell lines (KOC-5C and KOC-7C) in vitro. (b) KOC-5C or KOC-7C cells were transplanted into nude mice, and changes in tumor volume, tumor weight, apoptosis, necrosis, and microvessel density were investigated. The expression of angiogenesis factors was examined in the serum and the developed tumors. RESULTS: Both cell lines expressed IFNAR-2 mRNA, but its protein was detected only in KOC-7C. In KOC-7C cells, antiproliferative effects were observed in a time- and dose-dependent manner and cell division was blocked at the S phase. The KOC-7C tumors showed decreases in tumor volume and weight; a decreasing tendency in basic fibroblast growth factor (bFGF), vascular endothelial growth factor, and interleukin (IL)-8 protein expression in the tumor; a significant decrease in bFGF and IL-8 protein expression in the serum, and of microvessel density; and significant increase in apoptosis and necrosis in the tumor. In the KOC-5C tumors, these in vitro and in vivo changes were not apparent, and the antiproliferative effects of IFN-alphaCon1 were not obvious. CONCLUSIONS: IFN-alphaCon1 suppresses tumor proliferation by inducing apoptosis, blocking the cell cycle, and inhibiting tumor angiogenesis. Our findings show that the clinical efficacy of IFN-alphaCon1 can be predicted by examining IFNAR-2 expression on tumor cells, and the efficacy of IFN-alphaCon1 treatment can be evaluated by measuring serum bFGF and IL-8 levels.

Adenocarcinoma, Clear Cell↗
PubMed2004

Vascular endothelial growth factor C and vascular endothelial growth factor receptor 2 are related closely to the prognosis of patients with ovarian carcinoma.

BACKGROUND: The vascular endothelial growth factor (VEGF) family and VEGF receptors (VEGFR) play an essential role in the angiogenesis of both pathologic and nonpathologic conditions. However, the prognostic significance of VEGF and VEGFR expression in ovarian carcinoma is unclear. METHODS: The tissue expression levels of VEGF-A, VEGF-C, VEGFR-2, and VEGFR-3 in 80 specimens of ovarian carcinoma were examined immnohistochemically. The results obtained were analyzed clinicopathologically. RESULTS: VEGF-A, VEGF-C, VEGFR-2, and VEGFR-3 were expressed both in tumor cells and in adjacent endothelial cells of blood and lymph vessels. The tissue expressions of VEGF-C and VEGFR-2 were correlated significantly with tumor extension, including peritoneal metastases outside the pelvic cavity (P = 0.0010 and P = 0.0008, respectively), lymph node metastases (P = 0.0030 and P = 0.0018, respectively), and positive ascitic cytology (P = 0.025 and P = 0.0016, respectively). Conversely, there was no significant correlation between VEGF-A and VEGFR-3 expression and clinicopathologic features of ovarian carcinoma. Logistic regression analysis revealed that the expressions of VEGF-C and VEGFR-2 also were independent risk factors for peritoneal and lymph node metastases. Survival curves determined by the Kaplan-Meier method and in univariate analysis demonstrated that high expression levels of VEGF-C and VEGFR-2 were associated with the 5-year survival rate. In multivariate analysis, high expression levels of VEGF-C and VEGFR-2 emerged as independent indicators for disease-specific survival. CONCLUSIONS: High tissue expression of VEGF-C and VEGFR-2 reflects the aggressiveness of the spread of tumor in ovarian carcinoma. Thus, both have predictive value for identifying high-risk patients who have a poor prognosis.

Adult↗
PubMed2004

Humoral responses to peptides correlate with overall survival in advanced cancer patients vaccinated with peptides based on pre-existing, peptide-specific cellular responses.

PURPOSE: The aim of this study is to find a laboratory marker for overall survival in advanced cancer patients who were vaccinated with peptides based on pre-existing, peptide-specific CTL precursors in the circulation. EXPERIMENTAL DESIGN: A group of 113 patients with advanced cancer (28 colorectal, 22 prostate, 15 lung, 14 gastric, and 34 other cancers) was enrolled in a Phase I clinical study of peptide vaccination in which peptide-specific CTL precursors of prevaccination peripheral blood mononuclear cells were measured, followed by vaccination with these peptides (maximum of four). For cellular responses, pre and postvaccination (sixth) peripheral blood mononuclear cells were provided for measurement of both peptide-specific CTL precursors by IFN-gamma release assay and tumor reactivity by (51)Cr release assay. Delayed type hypersensitivity was also measured. For humoral response, pre and postvaccination (sixth) sera were provided for measurement of peptide-reactive IgG by an ELISA. RESULTS: The median survival time and 1-year survival rate of the total cases were 346 +/- 64.9 days and 44.6%, respectively, and those of patients vaccinated more than six times (n = 91) were 409 +/- 15 days and 54.4%, respectively. In these 91 patients, the overall survival of patients whose sera showed increased levels of peptide-reactive IgG (n = 60) was significantly more prolonged (P = 0.0003) than that of patients whose sera did not (n = 31), whereas none of cellular responses correlated with overall survival. CONCLUSIONS: Peptide-specific IgG in postvaccination sera could be a suitable laboratory maker for the prediction of prolonged survival in advanced cancer patients vaccinated with peptides based on pre-existing CTL precursors.

Adult↗
PubMed2004

Pulmonary metastasectomy for uterine cervical cancer: a multivariate analysis.

BACKGROUND: This study evaluated the results of resection of pulmonary metastases from cervical cancer. METHODS: A total of 7,748 patients with primary stage Ib or II cervical cancer underwent curative initial treatment consisting of radical hysterectomy or radiotherapy in 22 hospitals. Of the 7,748 patients, 29 (0.37%) patients had pulmonary metastases, which were detected after a disease-free period after initial treatment (radical hysterectomy or radiotherapy) and were resected with the intention to cure by June 30, 1998. RESULTS: The 5-year disease-free survival rate after pulmonary metastasectomy for all patients was 32.9%. Patients with one or two pulmonary metastases had a 5-year disease-free survival rate of 42.2% compared with 0% for patients with three or four metastases (p = 0.0003). Patients with squamous cell cancers had a 5-year disease-free survival rate of 47.4% compared with 0% for patients with adenosquamous cell cancers or adenocarcinoma (p = 0.0141). On multivariate analysis, the significant prognostic variables for disease-free survival were two or fewer metastases (p = 0.0232) and squamous cell cancer (p = 0.0168). CONCLUSIONS: Cervical cancer patients with pulmonary metastases after initial treatment (radical hysterectomy or radiotherapy) could expect to achieve long-term disease-free survival by pulmonary metastasectomy when there are two or fewer metastases diagnosed as squamous cell cancer.

Adenocarcinoma↗
PubMed2004

Co-expression of Y box-binding protein-1 and P-glycoprotein as a prognostic marker for survival in epithelial ovarian cancer.

OBJECTIVES: This study aimed to observe the expressions of Y box-binding protein-1 (YB-1) and P-glycoprotein (P-gp) in primary ovarian tumor and to determine whether they act as biomarkers for survival in epithelial ovarian cancer. METHODS: The expressions of YB-1 and P-gp were examined immunohistochemically in 59 patients who were treated from 1997 to 2000 at Kurume University Hospital. Samples were paraffin-embedded primary ovarian cancer tissue taken from the surgical specimens. RESULTS: Of the 59 primary ovarian tumors examined, 32 (54.2%) and 18 (30.5%) were positive for YB-1 and P-gp, respectively. Co-expression of these two proteins was observed in 20.3% (12/59) cases. Patients showing this co-expression had a worse 3-year survival than those without co-expression (40.0% vs. 73.1%, P = 0.0447). This co-expression significantly correlated with poor prognosis according to multivariate analysis (P = 0.0007). CONCLUSION: Co-expression of YB-1 and P-gp emerged as a promising relevant biomarker for unfavorable prognosis in ovarian cancer.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2004

Feasibility study of neoadjuvant chemotherapy followed by interval cytoreductive surgery for stage III/IV ovarian, tubal and peritoneal cancers: Japan Clinical Oncology Group Study JCOG0206.

A feasibility study was started in January 2003 on neoadjuvant chemotherapy (NAC) followed by interval cytoreductive surgery (ICS) and postoperative chemotherapy for stage III/IV müllerian carcinomas such as ovarian, tubal and peritoneal carcinomas. The purpose is to assess the safety and efficacy of the treatment starting with NAC and also to know whether we can accurately diagnose these advanced carcinomas by imaging studies, cytologic findings and tumor markers without staging laparotomy or laparoscopy. Fifty-six patients with advanced müllerian carcinomas will be recruited to the study. After confirmation of diagnosis by laparoscopic inspection and biopsies, patients undergo four cycles of chemotherapy as NAC, followed by ICS and an additional four cycles of post-surgical chemotherapy. The primary endpoint is proportion of clinical complete remission after accomplishment of the protocol treatment, while the major secondary endpoint is positive predictive value of diagnosis before laparoscopy regarding tumor origin, histology and stage. Based on the results of this study, we will conduct a phase III study to compare the treatment starting with NAC and primary cytoreductive surgery followed by post-surgical chemotherapy.

Adult↗
PubMed2004

Cisplatin, paclitaxel and escalating doses of doxorubicin (TAP) in advanced ovarian cancer: a phase I trial.

BACKGROUND: The objectives of this phase I trial were to determine the maximum tolerated dose (MTD) and the recommended dose (RD) for phase II/III trials of doxorubicin (DOX) combined with paclitaxel (PTX) and cisplatin (CDDP) in patients with advanced ovarian cancer (AOC). METHODS: Twenty-eight patients with stage III/IV AOC received fixed doses of PTX (110 mg/m(2) over 24 h on day 1) and CDDP (75 mg/m(2) on day 2) and an escalating dose of DOX (20, 30, 40 or 50 mg/m(2) on day 1) every 3 weeks. The patients received up to six cycles of chemotherapy. At level 1, one of the original dose-limiting toxicities (DLTs), grade (G) 4 neutropenia lasting for 4 days or longer, occurred in four of six patients. The criterion for DLT was amended to 'G4 neutropenia lasting for 8 days or longer accompanied with G4 leukopenia' and four additional patients were evaluated at level 1. RESULTS: According to the new criteria, DLT was observed only in one of nine patients except one ineligible patient at level 1 and two of six patients at level 4. G4 neutropenia and G4 leukopenia occurred in 85% and 44%, respectively, in the first course of chemotherapy. Non-hematological toxicity was generally mild or moderate. MTD was not determined at the planned dose levels. A clinical response was observed in 16 of 19 (84%) evaluable patients. Further dose escalation was not performed and RD was determined as level 4 because more than 30% of cycles required some modification of chemotherapy at level 4. CONCLUSION: The combination of TAP including 50 mg/m(2) of DOX is feasible and well tolerated as first line chemotherapy in AOC, warranting further study of this regimen.

Adolescent↗
PubMed2004

Immunological evaluation of vaccination with pre-designated peptides frequently selected as vaccine candidates in an individualized peptide vaccination regimen.

We previously conducted a trial of an 'individualized' regimen, in which cancer patients were vaccinated with peptides after the confirmation of pre-existing peptide-specific cytotoxic T lymphocyte (CTL) precursors. In this study, we performed a new trial of 'pre-designated' regimen, in which cancer patients were vaccinated with peptides that were frequently selected as vaccine candidates in the preceding individualized regimen. Eighteen cancer patients (10 with uterine cervical cancer and 8 with gastric cancer) were enrolled in the new regimen. The pre-designated regimen was well tolerated by all patients. Although peptide-specific CTL precursors and humoral responses increased in the majority of patients with the pre-designated regimen, neither of the responses correlated with clinical outcome. Three patients had long stable disease, and their pre-vaccination peripheral blood mononuclear cells contained peptide-specific CTL precursors reactive to more than 2 of 4 peptides. With the pre-designated regimen, the levels of pre-existing immunoglobulin G reactive to non-vaccinated peptides decreased in 5 of 15 patients with progressive disease, and their time to progression was very short, whereas such a decrease was rarely observed in the preceding individualized regimen. These results suggest that the pre-designated regimen can elicit a primary immune response, but may incidentally suppress pre-existing immune responses.

Adult↗
PubMed2004

The role of nuclear Y-box binding protein 1 as a global marker in drug resistance.

Gene expression can be regulated by nuclear factors at the transcriptional level. Many such factors regulate MDR1 gene expression, but what are the sequence elements and transcription factors that control the basal and inducible expression of this gene? The general principles through which transcription factors participate in drug resistance are now beginning to be understood. Here, we review the factors involved in the transcriptional regulation of the MDR1 gene. In particular, we focus on the transcription factor Y-box binding protein 1 and discuss the possible links between Y-box binding protein 1 expression and drug resistance in cancer, which are mediated by the transmembrane P-glycoprotein or non-P-glycoprotein.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2003

Weekly 1-h paclitaxel infusion in patients with recurrent endometrial cancer: a preliminary study.

BACKGROUND: The aim of this study was to evaluate the toxicity and efficacy of weekly paclitaxel in patients with recurrent endometrial cancer. METHODS: Nine patients with recurrent endometrial cancer who had previously received chemotherapy or radiotherapy participated in the study, between May 1999 and August 2001. Paclitaxel was given at a dose of 70 mg/m(2) as a 1-h infusion every week for at least 20 consecutive weeks unless lesions became progressive. Intravenous dexamethasone and cimetidine and oral diphenhydramine were administered 30 min before paclitaxel infusion. RESULTS: The nine patients received a total of 149 cycles of therapy. No hypersensitivity reactions were elicited. Grade 3 leukopenia, neutropenia, and anemia occurred in 22%, 33%, and 33% of the patients, respectively. Granulocyte colony-stimulating factor was required for two patients and no patients experienced febrile neutropenia. Neurotoxicity was commonly observed. Grade 1 peripheral neuropathy and myalgias were observed in 78% and 11% of the patients, respectively. No grade 3 or higher nonhematological toxicities were observed. Partial responses were seen in six of the nine patients (67%). The median progression-free interval was 8 months (range, 0-12 months) and the median overall survival was 10 months (range, 4-24 months). CONCLUSION: Weekly 1-h paclitaxel administration is considered safe and effective as a salvage therapy for recurrent endometrial cancer, with this schedule and delivery making its use more convenient and easier in the outpatient setting. The current results support further evaluation.

Adult↗
PubMed2003

Molecular pathology of atypical polypoid adenomyoma of the uterus.

Atypical polypoid adenomyoma (APA) is an uncommon and benign tumor of the uterus. In some patients, however, APA has been found to coexist with or to precede the development of an endometrioid adenocarcinoma similarly to complex endometrial hyperplasia. The molecular changes underlying the progression from APA to adenocarcinoma are unknown. DNA from paraffin-embedded tissue of 6 APAs was evaluated for microsatellite instability (MI), MLH-1 promoter hypermethylation, and CTNNB-1 mutations. Tissue sections were also subjected to MLH-1, MSH-2, and beta-catenin immunostaining. MI was not detected in any case. Two tumors exhibited MLH-1 promoter hypermethylation and showed focal negative MHL-1 immunostaining; 1 of these showed marked architectural complexity and cellular pleomorphism. Five cases presented beta-catenin nuclear immunoreactivity, but none of them had CTNNB-1 mutations. The results of this study suggest that APA and complex endometrial hyperplasia may share some molecular alterations. Some APAs exhibit MLH-1 promoter hypermethylation with focal lack of MLH-1 immunostaining, a molecular abnormality involved in the transition from complex atypical hyperplasia to endometrioid adenocarcinoma.

Adaptor Proteins, Signal Transducing↗
PubMed2003

Primary leiomyoma of the ovary--a report of 2 resected cases.

Leiomyoma of the ovary is relatively rare and its origin is still controversial. Here, we report 2 cases of ovarian leiomyoma. Case 1, a 59-year-old woman who complained of abdominal distention. Ultrasonography and computed tomography revealed a large solid mass in the lower abdomen. The mass was diagnosed as uterine myoma preoperatively, but it turned out to be a left ovarian tumor at laparotomy. The tumor was about an adult-head size, grayish, elastic hard, and solid. In case 2, a fist-sized mass was accidentally detected in the right ovary of a 84-year-old woman during laparotomy for rectal cancer. Histologically both tumors were composed of solid proliferation of short spindle-shaped cells, that formed interlacing fascicles and showed varying degrees of hyalinization. Both tumors were diagnosed as leiomyoma. Although this tumor is rather infrequent, it is necessary to consider leiomyoma for differential diagnosis, when a solid tumor is detected in the ovary.

Aged↗
PubMed2002

Increased nuclear localization of transcription factor YB-1 in acquired cisplatin-resistant ovarian cancer.

PURPOSE: Nuclear expression of Y box-binding protein (YB-1), a member of the DNA-binding protein family, was recently reported to have a much higher concentration in cisplatin-resistant cancer cell lines than in their drug-sensitive parental counterparts, suggesting the ability to induce cisplatin resistance. Ovarian cancer has been generally treated with cisplatin-based chemotherapy and often recurs due to acquired cisplatin resistance. The aim of our study is to elucidate the association between nuclear YB-1 and cisplatin resistance in human ovarian cancer using cultured cell lines and surgical specimens. METHODS: Intracellular YB-1 localization was examined by Western blot analysis for both cisplatin sensitive and resistant human ovarian cancer cell lines. Moreover, 35 pairs of surgical specimens derived from primary and matched recurrent ovarian cancers of the same patient were evaluated for their nuclear YB-1 expression by immunohistochemical staining. RESULTS: Western blot analysis for nuclear and cytoplasmic extracts indicated that cisplatin-resistant cells showed much higher nuclear YB-1 expression than sensitive parental cells. Immunohistochemical analysis showed that ten paired cases turned from negative nuclear YB-1 in primary lesions to positive nuclear YB-1 in recurrent lesions, whereas only two paired cases showed a reverse turn from positive to negative. CONCLUSIONS: The expression of YB-1 in the nucleus seems to be associated with acquired cisplatin resistance in ovarian cancers. Nuclear YB-1 might be a useful predictive marker indicating cisplatin sensitivity and/or a target molecule to treat recurring ovarian cancers by cisplatin-based second-line chemotherapy.

Antineoplastic Agents↗
PubMed2002

PTEN expression is associated with prognosis for patients with advanced endometrial carcinoma undergoing postoperative chemotherapy.

The prognostic significance of PTEN expression in endometrial carcinoma has not been clear. We conducted the present study to clarify the relationship between PTEN expression and prognosis in advanced endometrial carcinoma. Of 784 patients with endometrial carcinoma who underwent primary treatment between 1985 and 2000 at 5 institutions, 98 pure endometrioid carcinomas with retroperitoneal lymph node metastasis were provided for our study. PTEN expression was determined by immunohistochemic staining. Negative or mixed PTEN staining was observed in 64 (65.3%) patients. The survival rate for PTEN-positive patients was significantly higher than that for PTEN-negative or -mixed patients. PTEN-staining status was not associated with patient age, International Federation of Gynecology and Obstetrics (FIGO) stage, myometrial invasion or histologic grade. Of the 98 patients, 87 received radiation therapy (n = 25) or chemotherapy (n = 62) after surgery. PTEN expression did not relate to survival for patients receiving radiation therapy. In contrast, the survival rate for PTEN-positive cases was significantly higher than that for PTEN-negative or -mixed cases when patients underwent chemotherapy (62.4% vs. 11.8%). Subsequent multivariate analysis revealed that PTEN staining was an independent prognostic factor for patients undergoing chemotherapy. PTEN-positive staining was a significant prognostic indicator of favorable survival for patients with advanced endometrial carcinoma who underwent postoperative chemotherapy.

Adult↗