Fukuko Moriya

Kurume University, Куруме, Fukuoka, Japan

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Publications (39)109.63 Total impact

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    ABSTRACT: Anaplastic lymphoma kinase (ALK) translocation renal cell carcinomas (RCCs) have been reported by several independent groups in recent times. The clinical behavior and histopathologic characteristics of these carcinomas are not fully understood because of the paucity of cases reported. Here, we describe 2 cases of RCC harboring a novel striatin (STRN)-ALK fusion. The first case was a 33-year-old woman with no sickle cell trait who underwent nephrectomy for right renal mass and had late recurrence in para-aortic lymph nodes twice 10 and 12 years after initial surgery. After the second recurrence, she was carefully observed without any treatment. Twenty-six years after the initial nephrectomy, the second para-aortic lymphadenectomy was performed, and gastrectomy was performed for newly developed primary gastric cancer. The resected para-aortic lymph nodes were largely replaced by metastatic carcinoma. The second case was a 38-year-old man with no sickle cell trait who underwent cytoreductive nephrectomy followed by sunitinib therapy for metastatic RCC. In both cases, the tumor showed solid, papillary, tubular, and mucinous cribriform structures. Psammoma bodies were occasionally seen in the stroma. Tumor cells had a large nucleus and prominent nucleoli with predominantly eosinophilic cytoplasm. Rhabdoid cells and signet-ring cells were also observed. Intracytoplasmic mucin deposition and background mucinous stroma were confirmed. In the second case, tumor necrosis was seen in some areas. Tumor cells exhibited diffuse positive staining for ALK in both cases. ALK translocation was confirmed by fluorescent in situ hybridization, and further gene analysis revealed a STRN-ALK fusion. These cases provide great insights into ALK translocation RCCs.
    No preview · Article · Feb 2016 · The American journal of surgical pathology
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    ABSTRACT: This study investigated the effect of metronomic cyclophosphamide (CPA) in combination with personalized peptide vaccination (PPV) on regulatory T cells (Treg) and myeloid-derived suppressor cells (MDSC), and whether it could improve the antitumor effect of PPV. Seventy patients with metastatic castration-resistant prostate cancer were randomly assigned (1:1) to receive PPV plus oral low-dose CPA (50 mg/day), or PPV alone. PPV treatment used a maximum of four peptides chosen from 31 pooled peptides according to human leukocyte antigen types and antigen-specific humoral immune responses before PPV, for 8 subcutaneous weekly injections. Peptide-specific cytotoxic T lymphocyte (CTL) and immunoglobulin G responses were measured before and after PPV. The incidence of grade 3 or 4 hematologic adverse events was higher in the PPV plus CPA arm than in the PPV alone arm. Decrease in Treg and increase in MDSC were more pronounced in PPV plus CPA treatment than in PPV alone (p = 0.036 and p = 0.048, respectively). There was no correlation between the changes in Treg or MDSC and CTL response. There was no difference in positive immune responses between the two arms, although overall survival in patients with positive immune responses was longer than in those with negative immune responses (p = 0.001). Significant differences in neither progression-free survival nor overall survival were observed between the two arms. Low-dose CPA showed no change in the antitumor effect of PPV, possibly due to the simultaneous decrease in Treg and increase in MDSC, in patients under PPV.
    No preview · Article · Jan 2016 · Cancer Immunology and Immunotherapy
  • Masanori Noguchi · Noriko Koga · Fukuko Moriya · Kyogo Itoh
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    ABSTRACT: Although treatment options for castration-resistant prostate cancer (CRPC) have increased over the last decade, there remains a need for strategies that can provide durable disease control and long-term benefit. Recently, immunotherapy has emerged as a viable and attractive strategy for the treatment of CRPC. To date, there are multiple strategies to target the immune system, and several approaches including therapeutic cancer vaccines and immune checkpoint inhibitors have been most successful in clinical trials. With regard to this, we report the results of the most recent clinical trials investigating immunotherapy in CRPC and discuss the future development of immunotherapy for CRPC, as well as the potential importance of biomarkers in the future progress of this field.
    No preview · Article · Dec 2015 · Immunotherapy
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    ABSTRACT: Purpose: The prognosis of platinum-based chemotherapy-resistant metastatic urothelial cancer of the bladder remains poor. Personalized selection of the right peptides for each patient could be a novel approach for a cancer vaccine to boost anticancer immunity. Experimental design: In this randomized, open-label, phase II study, patients ages ≥18 years with progressive bladder cancer after first-line platinum-based chemotherapy were randomly assigned (1:1) to receive personalized peptide vaccination (PPV) plus best supportive care (BSC) or BSC. PPV treatment used a maximum of four peptides chosen from 31 candidate peptides according to human leukocyte antigen types and peptide-reactive IgG titers, for 12 s.c. injections (8 injections, weekly; 4 injections, bi-weekly). The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), immune response, and toxicity. Results: Eighty patients were randomly assigned to receive either PPV plus BSC (n = 39) or BSC (n = 41). No significant improvement in PFS was noted [HR, 0.7; 95% confidence interval (CI), 0.4-1.2, P = 0.17]. For the secondary endpoints, PPV plus BSC significantly prolonged OS compared with BSC (HR, 0.58; 95% CI, 0.34-0.99, P = 0.049), with median OS of 7.9 months (95% CI, 3.5-12.0) in the PPV plus BSC and 4.1 months (95% CI, 2.8-6.9) in the BSC. PPV treatment was well tolerated, without serious adverse drug reactions. Conclusions: PPV could not prolong PFS, but OS appeared to be improved with low toxicity and immune responses. Further large-scale, randomized trials are needed to confirm these results. Clin Cancer Res; 1-7. ©2015 AACR.
    Full-text · Article · Nov 2015 · Clinical Cancer Research
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    ABSTRACT: The present study aimed to examine the association between 18F-fluorodeoxyglucose (18F-FDG) uptake and cell proliferation markers; in addition, the correlation between 18F-FDG uptake and biological characteristic in patients with renal cell carcinoma (RCC) was investigated using dual-phase 18F-FDG-positron emission tomography/computed tomography (PET/CT). Dual-phase 18F-FDG PET/CT was performed on 31 RCC patients and the maximum standardized uptake values at 1 h (SUV1) and 2 h (SUV2) as well as the retention index (RI; %) in the primary tumors were calculated. Monoclonal antibodies for Ki-67, minichromosome maintenance 2 (MCM2) and topoisomerase II α (topo II α) were used to assess the expression levels of their respective proteins in excised tumor tissue using immunohistochemistry. The results demonstrated that RI and SUV2 in patients with Stage I/II + grade 1 (G1) RCC were significantly decreased compared with all patients with other stages/grades (RI, P=0.0065; SUV2, P=0.043); in addition, significantly increased uptake and RI were detected in patients with metastases compared with patients without metastases (SUV1, P=0.029; SUV2, P=0.0003; RI, P<0.001). All proliferation markers significantly correlated with RI (Ki-67, r=0.501, P=0.004; MCM2, r=0.359, P=0.047; topo II α, r=0.402, P=0.024), while SUV1 and SUV2 correlated with Ki-67 only. In conclusion, the results of the present study demonstrated that dual-phase 18F-FDG-PET/CT was more useful for predicting cell proliferation in RCC compared with single-phase imaging alone. However, follow-ups are required in order to determine whether dual-phase 18F-FDG-PET/CT provides independent prognostic information.
    Full-text · Article · Jun 2015 · Oncology letters
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    ABSTRACT: The heterogeneity expression of tumor-associated antigens (TAA) and variability of human T cell repertoire suggest that effective cancer vaccine requires induction of a wide breadth of cytotoxic T lymphocyte (CTL) specificities. This can be achieved with vaccines targeting multiple TAA. We evaluated the safety and immune dynamics of a cancer vaccine consisting of 20 mixed peptides (KRM-20) designed to induce CTLs against 12 different TAA in patients with castration-resistant prostate cancer (CRPC). Patients received each of three different randomly assigned doses of KRM-20 (6, 20, or 60 mg) once a week for 6 weeks. KRM-20 was applicable for patients with positive human leukocyte antigen (HLA) A2, A3, A11, A24, A26, A31 or A33 alleles, which cover the majority of the global population. To evaluate the minimum immunological effective dose (MIED), peptide-specific CTL and immunoglobulin G (IgG) responses, and immune suppressive subsets were evaluated during the vaccination. Total of 17 patients was enrolled. No serious adverse drug reactions were encountered. The MIED of KRM-20 in CTL or IgG response calculated by logistic regression model was set as 16 or 1.6 mg, respectively. The frequency of immune suppressive subsets was fewer in the 20 mg cohort than that in 6 or 60 mg cohort. Clinical responses determined by prostate-specific antigen levels were two partial responses (from the 20 mg cohort), five no changes and ten progressive diseases. Twenty milligrams of KRM-20 could be recommended for further studies because of the safety and ability to augment CTL activity.
    No preview · Article · Feb 2015 · Cancer Immunology and Immunotherapy
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    ABSTRACT: Cancer vaccine is one of the attractive treatment modalities for patients with castration-resistant prostate cancer (CRPC). However, because of delayed immune responses, its clinical benefits, besides for overall survival (OS), are not well captured by the World Health Organization (WHO) and Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Several surrogate markers for evaluation of cancer vaccine, including prostate-specific antigen doubling time (PSADT), are currently sought. The purpose of this study was to assess prospectively the PSA kinetics and immune responses, as well as the efficacy, safety, and biomarkers of personalized peptide vaccination (PPV) in progressive CRPC. One hundred patients with progressive CRPC were treated with PPV using 2-4 positive peptides from 31 candidate peptides determined by both human leukocyte antigen (HLA) class IA types and the levels of immunoglobulin G (IgG) against each peptide. The association between immune responses and PSADT as well as overall survival (OS) was studied. PPV was safe and well tolerated in all patients with a median survival time of 18.8 months. Peptide-specific IgG and T-cell responses strongly correlated with PSADT (p < 0.0001 and p = 0.0007, respectively), which in turn showed correlation with OS (p = 0.018). Positive IgG responses and prolongation of PSADT during PPV were also significantly associated with OS (p = 0.001 and p = 0.004) by multivariate analysis. PSADT could be an appropriate surrogate marker for evaluation of the clinical benefit of cancer vaccine. Further randomized trials are needed to confirm these results.Trial registration: UMIN000001850.
    Full-text · Article · Dec 2013 · BMC Cancer

  • No preview · Article · Apr 2013 · The Journal of Urology
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    ABSTRACT: Treating extended prostatic small cell neuroendocrine carcinoma (PSCNC) is extremely difficult and no standard treatment has yet been established. We experienced a case of advanced mixed-type PSCNC in which the patient achieved long-term survival and local control following combined therapy. Locally advanced PSCNC causing lower urinary obstruction was detected during androgen-ablation therapy for stage D2 mixed adenocarcinoma PSCNC. The patient was treated with intra-arterial infusion chemotherapy using a reservoir system and external-beam radiotherapy (EBRT) to the whole pelvis and local tumor. After chemoradiotherapy, the patient's lower urinary obstruction was reduced and did not return during the remaining 40 months of the patient's life. The patient survived for 70 months following the start of the androgen-ablation therapy. The present study reports a useful treatment for advanced mixed-type PSCNC, androgen-ablation therapy and chemoradiotherapy. The present results also suggest that the prognostic factors for advanced mixed-type PSCNC are the sensitivity of the conventional adenocarcinoma to androgen-ablation therapy, degree of metastasis and extent of the small cell neuroendocrine carcinoma component.
    Preview · Article · Mar 2013 · Oncology letters
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    ABSTRACT: In general, only ≤5% of patients with renal cell carcinoma (RCC) develop paraneoplastic erythropoietin (EPO) overproduction-induced polycythemia. However, a number of reports on EPO-producing RCC are available. The present study aimed to report the first case of a patient demonstrating a therapeutic effect on EPO-producing advanced RCC, subsequent to targeted pre-surgical sunitinib therapy, with a review of the literature. The patient involved was a 62-year-old male who presented with a malformation of the left scrotum. Examination revealed a tumor of 73 mm in diameter along with lymph node metastasis. The histological examination indicated a clear cell RCC containing viable cells as well as hemorrhage and necrosis. EPO in cancer cells was confirmed by immunohistochemistry. Subsequently, a case of EPO-producing RCC with polycythemia was diagnosed. The EPO-producing RCC was successfully treated following targeted presurgical therapy with sunitinib.
    Full-text · Article · Jan 2013 · Molecular and Clinical Oncology
  • M. Noguchi · S. Suekane · F. Moriya · T. Sasada · A. Yamada · K. Itoh

    No preview · Conference Paper · Oct 2012
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    ABSTRACT: Because only a subset of patients show clinical responses to peptide-based cancer vaccination, it is critical to identify biomarkers for selecting patients who would most likely benefit from this treatment. The authors characterized the gene expression profiles in peripheral blood of vaccinated patients to identify biomarkers to predict patient prognosis. Peripheral blood was obtained from advanced castration-resistant prostate cancer patients, who survived for >900 days (long-term survivors, n = 20) or died within 300 days (short-term survivors, n = 20) after treatment with personalized peptide vaccination. Gene expression profiles in prevaccination and postvaccination peripheral blood mononuclear cells (PBMCs) were assessed by DNA microarray. There were no statistically significant differences in the clinical or pathological features between the 2 groups. Microarray analysis of prevaccination PBMCs identified 19 genes that were differentially expressed between the short-term and long-term survivors. Among the 15 up-regulated genes in the short-term survivors, 13 genes, which were also differentially expressed in postvaccination PBMCs, were associated with gene signatures of granulocytes. When a set of 4 differentially expressed genes were selected as the best combination to determine patient survival, prognosis was correctly predicted in 12 of 13 patients in a validation set (accuracy, 92%). These results suggested that abnormal granulocytes present in the PBMC faction may contribute to poor prognosis in advanced prostate cancer patients receiving personalized peptide vaccination. Gene expression profiling in peripheral blood might thus be informative for devising better therapeutic strategies by predicting patient prognosis after cancer vaccines.
    Full-text · Article · Jun 2012 · Cancer
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    ABSTRACT: Docetaxel-based chemotherapy (DBC) showed limited clinical efficacy for castration-resistant prostate cancer (CRPC) patients. To explore cancer vaccine as a new treatment modality, we conducted a phase II study of personalized peptide vaccine (PPV) for DBC-resistant CRPC patients. Twenty DBC-resistant CRPC patients and 22 patients with no prior DBC, as a control, were treated with PPV using peptides chosen from 31 peptides in patients, respectively. Cytokines, inflammatory markers, and immune responses were measured as candidate biomarkers. DBC-resistant CRPC patients without PPV was set as a historical control for evaluation of clinical benefit of PPV. Median overall survival (OS) time from the first vaccination was 14.8 months or not reached in DBC-resistant CRPC patients and patients with no prior DBC (log-rank; P = 0.07), respectively. Median OS time from the first day of progression disease was 17.8 and 10.5 months in DBC-resistant CRPC patients receiving PPV and those with no PPV (P = 0.1656), respectively. Elevated IL-6 levels before vaccination was an unfavorable factor for OS of DBC-resistant CRPC patients (P = 0.0161, hazard ratio (HR): 0.024, 95% CI:0.001-0.499) as well as all 42 patients with PPV(P = 0.0011, HR: 0.212, 95% CI:0.068-0.661) by multivariable analysis. Further clinical study of PPV is recommended for DBC-resistant CRPC patients, because of the safety and possible prolongation of MST. Control of elevated IL-6 by combined therapy may provide much better clinical outcome.
    No preview · Article · Jun 2012 · The Prostate
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    ABSTRACT: Recently in Japan, most therapy for advanced renal cell carcinoma (RCC) involves a molecular targeted therapeutic agent However, we sometimes experience cases where the administration of such drugs is difficult to continue due to severe adverse effects. Accordingly, immunotherapy for advanced RCC needs to be reconsidered. To explore cancer vaccine as a new treatment modality, we conducted a phase II study of personalized peptide vaccine (PPV) for advanced renal cell carcinoma patients. Therapeutic cancer vaccine therapy has undergone clinical trials for renal cell carcinoma, and is expected to become the fourth therapeutic method following surgery, radiotherapy and chemotherapy. Five advanced renal cell carcinoma patients were treated with PPV using peptides chosen from among 31 peptides in the patients. PPV was safe and well tolerated with no severe adverse effects in any of the patients. The overall survival (OS) time from the first vaccination was 30+, 13, 21+, 20+ and 8+ months in the five advanced renal cell carcinoma patients. Further clinical study of PPV is recommended for advanced renal cell carcinoma patients, with a view to the safety and possible prolongation of median survival time.
    No preview · Article · May 2012 · Nishinihon Journal of Urology

  • No preview · Article · Apr 2012 · The Journal of Urology
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    ABSTRACT: Adenoma of the retinal pigment epithelium (RPE) is a rare intraocular tumor that can simulate other pigmented tumors such as choroidal melanoma. We report a case of non-pigmented adenoma of the RPE initially diagnosed as choroidal hemangioma. A 42-year-old woman presented to Kurume University Hospital in November 1992 with an orange-yellow tumor nasal to the optic disc in the left fundus. The tumor was 9.0 × 9.0 mm in diameter, 6.0 mm thick, and was characterized by high intensity on T1-weighted magnetic resonance imaging (MRI), low intensity on T2-weighted MRI, and enhancement on gadolinium MRI. Fluorescein angiography revealed early hypofluorescence and late hyperfluorescence of the tumor and retinal feeder vessels. By April 1996, exudate had developed around the tumor margins. The patient was treated with external beam radiation therapy (20 Gy) in July 1996, but the tumor did not diminish in size. Subsequently, she developed extensive loss of vision due to total retinal detachment. Accordingly, her left eye was enucleated in June 2005 because of severe ocular pain due to absolute glaucoma. Histopathological examination indicated that the tumor was contiguous with the normal surrounding RPE and was composed of cords and tubules of mostly non-pigmented spindle-shaped cells with round to oval nuclei and a small amount of cytoplasm containing melanin granules. The tumor cells were immunoreactive for vimentin, S-100 protein, and cytokeratin 18. The final diagnosis was adenoma of the RPE. Adenoma of the retinal pigment epithelium may be associated with incompetent vessels leading to serous retinal detachment and extensive visual loss, and may exhibit clinical characteristics similar to choroidal hemangioma.
    Preview · Article · Mar 2012 · Clinical Ophthalmology
  • K. Itoh · F. Moriya · S. Suekane · K. Matsuoka · M. Noguchi
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    ABSTRACT: The field of cancer vaccines has moved forward dramatically since 1991, when Boon and colleagues reported their discovery of the first tumour-associated antigen. Numerous tumour-associated antigens have since been identified and some of them have been clinically tested with encouraging results in immunotherapy against patients with various types of cancer. Indeed, several immunotherapy strategies for prostate cancer, such as single-peptide-based vaccine, multiple-peptide-based vaccine, cell-based vaccine, viral vaccine, antibody-based therapy and their combination with other therapies, have been evaluated. We also reported the clinical outcome along with the safety and immune responses of the personalized peptide vaccination (PPV) alone, as well as combined with other therapies. More recently, the US Food and Drug Administration (FDA) recently approved two novel immunotherapy agents, sipuleucel-T and ipilimumab, which showed a survival benefit for patients with metastatic prostate cancer and melanoma, respectively. These cancer vaccines, however, had several limitations with regard to clinical efficacy, cost, and HLA-restriction. To overcome these limitations, new types of cancer vaccine are under basic and clinical investigation. This article reviews the current status of cancer vaccines, particularly peptide-based vaccine, and discusses the future direction of therapeutic cancer vaccines.
    No preview · Article · Mar 2012 · Nishinihon Journal of Urology
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    ABSTRACT: A 78-year-old man underwent surgery for colon cancer in 1994, and in 1996 he hemodialysis therapy due to end-stage renal failure. Abdominal ultrasound imaging demonstrated left adrenal gland swelling and computed tomographic scan showed a φ33 × 36 mm size mass on the left adrenal gland in January, 2008. After some endocrine examinations, we diagnosed the adrenal mass as a left nonfunctional adrenal tumor. The size of the adrenal tumor had increased to φ 65 × 45 mm in October, 2010. At the same time we recognized a renal tumor on the same side kidney and diagnosed it as renal cancer. We performed a left nephrectomy and adrenalectomy. Histological evaluation showed an adrenal hemorrhage without malignant cells and renal cell carcinoma It was difficult for us to identify the bleeding site of the adrenal hemorrhage. Finally, we diagnosed the renal tumor as papillary renal cell carcinoma type 2.
    No preview · Article · Feb 2012 · Nishinihon Journal of Urology
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    ABSTRACT: The prognosis of standard therapy-resistant urothelial carcinoma (UC) remains poor. To explore cancer vaccine as a new treatment modality, we conducted a phase II study of personalized peptide vaccine (PPV) for standard therapy-resistant UC patients. Therapeutic cancer vaccine therapy has undergone clinical trials for urothelial carcinoma, and is being developed as a drug so that it can supply. It is expected to become the fourth therapeutic method following surgery, radiotherapy and chemotherapy. Twenty-five standard therapy-resistant UC patients were treated with PPV using peptides chosen from among 31 peptides in the patients. This study protocol was approved by the institutional ethical review boards of Kurume University, and conducted in accordance with the Declaration of Helsinki. Written informed consent was obtained from all patients they participated in this clinical trial. Peptide vaccination was safe and well tolerated, with no severe adverse events in any of the patients. Median overall survival (OS) time from the first vaccination was 11. 3 months in the standard therapy-resistant UC patients. Increased anti-peptide IgG titer was revealed in ten patients (40%) out of twenty-five patients at post 6 th vaccination, and in six patients (100%) out of six patients at post 12 th vaccination. Further clinical study of PPV is recommended for standard therapy-resistant UC patients, with a view of the safety and possible prolongation of MST.
    No preview · Article · Feb 2012 · European Urology Supplements
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    Full-text · Article · Jun 2011 · International Journal of Urology