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Daisuke Nonaka

Publications and source records attributed to Daisuke Nonaka.

16 recordsLinked to original sources
PubMed2006

Association of antigen-processing machinery and HLA antigen phenotype of melanoma cells with survival in American Joint Committee on Cancer stage III and IV melanoma patients.

Because changes in the expression level of antigen-processing machinery (APM) components and HLA class I and II antigens in melanoma cells are expected to affect their interactions with the immune system of the host, we assessed the clinical relevance of quantitative variations in the expression of these molecules in melanoma lesions. Short-term (<10 in vitro passages) melanoma cell lines isolated from 85 American Joint Committee on Cancer (AJCC) stage III and IV patients were stained with APM component and HLA class I antigen-specific and HLA class II antigen-specific monoclonal antibodies and analyzed by flow cytometry. The phenotype of all tumors was characterized by intertumor and intratumor heterogeneity in the expression of all the markers and by significant correlations in the level of expression of markers belonging to the HLA class I antigen-processing and presentation pathway. Hierarchical clustering of the mean fluorescence intensity data defined two main clusters of tumors. The corresponding groups of patients differed significantly in the overall survival but not in other relevant clinical variables, including AJCC stage and therapy received after surgery. Cox regression analysis showed that beta2-microglobulin and HLA class II antigen expression were significantly associated with patients' survival. This evidence was corroborated by the immunohistochemical analysis for HLA class II antigen expression of melanoma lesions from an unrelated group of 52 AJCC stage III and IV patients. These results suggest that quantitative variations in APM component and HLA expression in melanoma lesions from AJCC stage III and IV patients may have an effect on the clinical course of the disease.

Animals↗
PubMed2006

Prognostic analysis of clinicopathologic factors in 49 patients with diffuse malignant peritoneal mesothelioma treated with cytoreductive surgery and intraperitoneal hyperthermic perfusion.

BACKGROUND: Diffuse malignant peritoneal mesothelioma (DMPM) is a subset of peritoneal mesothelioma with a poor clinical outcome. We performed a prognostic analysis in a cohort of DMPM patients treated homogeneously by cytoreductive surgery and intraperitoneal hyperthermic perfusion (IPHP). METHODS: Forty-nine DMPM patients who underwent 52 consecutive procedures were enrolled onto the study. Cytoreductive surgery was performed according to the peritonectomy technique, and the IPHP was performed with cisplatin plus doxorubicin or cisplatin plus mitomycin C. We assessed the correlation of the clinicopathologic variables (previous surgical score, age, sex, performance status, previous systemic chemotherapy, carcinomatosis extension, completeness of cytoreduction, IPHP drug schedule, mitotic count [MC], nuclear grade, and biological markers [epidermal growth factor receptor, p16, matrix metalloproteinase 2 and matrix metalloproteinase 9]) with overall and progression-free survival. RESULTS: The mean age was 52 years (range, 22-74 years). The mean follow-up was 20.3 months (range, 1-89 months). Regarding the biological markers, the rates of immunoreactivity of epidermal growth factor receptor, p16, matrix metalloproteinase 2, and matrix metalloproteinase 9 were 94%, 60%, 100%, and 85%, respectively. The strongest factors influencing overall survival were completeness of cytoreduction and MC, whereas those for progression-free survival were performance status and MC. No biological markers were shown to be of prognostic value. CONCLUSIONS: Completeness of cytoreduction, performance status, and MC seem to be the best determinants of outcome. These data warrant confirmation by a further prospective formal trial. No biological markers presented a significant correlation with the outcome. The overexpression of epidermal growth factor receptor, matrix metalloproteinase 2, and matrix metalloproteinase 9 and absent or reduced expression of p16 might be related to the underlining tumor kinetics of DMPM and warrant further investigation with other methods.

Adult↗
PubMed2005

Diffuse malignant mesothelioma of the peritoneum: a clinicopathological study of 35 patients treated locoregionally at a single institution.

BACKGROUND: In the current study, the authors report the clinicopathologic features of patients with peritoneal diffuse malignant mesothelioma (DMM) who were treated in a uniform fashion at a single institution to assess prognostic factors. METHODS: Thirty-five patients were treated with cytoreductive surgery (CRS) and intraperitoneal hyperthermic perfusion (IPHP). The tumors were classified into epithelial, sarcomatoid, and biphasic types. Immunohistochemistry stains were performed for calretinin, WT-1, pCEA, Ber-EP4, epidermal growth factor receptor (EGFR), p16, matrix metalloprotease-2 (MMP-2), and MMP-9. Statistical correlation was evaluated for age, gender, completeness of cytoreduction (CC), tumor histotype, mitotic count (MC), necrosis, nuclear grade (NG), and biologic markers with regard to overall survival (OS) and progression-free survival (PFS). RESULTS: The patient group was comprised of 15 men and 20 women with a median age of 52 years (range, 24-73 yrs). Twenty-five patients underwent optimal cytoreduction. There were 32 epithelial tumors and 3 biphasic tumors, and 3 patients had an NG of 1, 19 had an NG of 2, and 13 had an NG of 3. The mean MC was 14.1 (range, 0-160 per 50 high-power fields). Necrosis was present in 11 cases. All the tumors were found to be positive for calretinin and WT-1 and were negative for pCEA and Ber-EP4. The NG and MC were found to be significantly associated with OS (P = 0.02 and P = 0.01, respectively) whereas CC was found to be associated with both OS (P = 0.05) and PFS (P = 0.03). No biologic markers were found to be of prognostic significance. CONCLUSIONS: The results of the current study indicate that NG, MC, and CC may be useful prognostic factors in patients treated with CRS and IPHP. The expression of EGFR, MMP-2, and MMP-9 and absent and/or reduced expression of p16 in DMMs confirms the results of previous studies suggesting their role in tumor pathogenesis and kinetics.

Adult↗
PubMed2005

Apoptotic and cell cycle regulatory markers in uterine leiomyosarcoma.

OBJECTIVES: The primary aim of this study was to investigate the expression of apoptotic and cell cycle regulators p53, p21, p27, bax, and bcl-2 in uterine leiomyosarcoma in order to identify molecular pathways that possibly could be important in the development of leiomyosarcoma. A secondary aim was to examine if the apoptotic and cell cycle regulatory protein expression profile of uterine leiomyosarcoma is potentially useful for clinical prognostic purposes. METHODS: A tissue microarray representing 36 uterine leiomyosarcomas and 19 uterine leiomyomas was created with 3 representative cores from each tumor. Immunohistochemical staining was performed for bcl-2, bax, p21, p27, and p53 using standard techniques. Staining was scored 0-12 for each marker, 0-3 being negative and 4-12 positive. Outcome analyses were performed only for leiomyosarcomas. First recurrence was determined from the time of initial diagnosis. Survival was determined from the time of initial diagnosis to last follow-up. RESULTS: Associations were found between disease type (leiomyosarcoma vs. leiomyoma) and the positivity status of p21 (43% vs. 0%, P < 0.001), p53 (54% vs. 0%, P < 0.001), and bax (34% vs. 94%, P < 0.001). bcl-2-positive leiomyosarcoma was associated with a longer time to recurrence (P = 0.02) in a univariate analysis. In a multivariate analysis, tumor stage was the only independent significant prognostic factor (P = 0.002). CONCLUSION: The significant differential expression of apoptotic and cell cycle regulatory proteins in uterine leiomyosarcoma as compared to benign smooth muscle tumors suggests that pathways involving these proteins may be important in the development of malignant disease and, therefore, could be potential targets for molecular therapies.

Adult↗
PubMed2005

A phase II trial of vaccination with autologous, tumor-derived heat-shock protein peptide complexes Gp96, in combination with GM-CSF and interferon-alpha in metastatic melanoma patients.

The aim of this study was to determine the immunogenicity and antitumor activity of autologous, tumor-derived heat shock protein gp96-peptide complex vaccine (HSPPC-96; Oncophage given with GM-CSF and IFN-alpha in pre-treated metastatic (AJCC stage IV) melanoma patients. Patients underwent surgical resection of metastatic lesions for HSPPC-96 production. HSPPC-96 was administered subcutaneously (s.c.) in four weekly intervals (first cycle). Patients with more available vaccine and absence of progressive disease received four additional injections in 2-week intervals (second cycle) or more. GM-CSF was given s.c. at the same site at days -1, 0 and +1, while IFN-alpha (3 MU) was administered s.c. at a different site at days +4 and +6. Antigen-specific anti-melanoma T and NK lymphocyte response was assessed by enzyme-linked immunospot assay on peripheral blood mononuclear cells obtained before and after vaccination. Thirty-eight patients were enrolled, 20 received at least four injections (one cycle) of HSPPC-96 and were considered assessable. Toxicity was mild and most treatment-related adverse events were local erythema and induration at the injection site. Patients receiving at least four injections of HSPPC-96 were considered evaluable for clinical response: of the 18 patients with measurable disease post surgery, 11 showed stable disease (SD). The ELISPOT assay revealed an increased class I HLA-restricted T and NK cell-mediated post-vaccination response in 5 out of 17 and 12 out of the 18 patients tested, respectively. Four of the five class I HLA-restricted T cell responses fall in the group of SD patients. Vaccination with autologous HSPPC-96 together with GM-CSF and IFN-alpha is feasible and accompanied by mild local and systemic toxicity. Both tumor-specific T cell-mediated and NK cell responses were generated in a proportion of patients. Clinical activity was limited to SD. However, both immunological and clinical responses were not improved as compared with those recorded in a previous study investigating HSPPC-96 monotherapy.

Adjuvants, Immunologic↗
PubMed2005

Constitutive expression and costimulatory function of LIGHT/TNFSF14 on human melanoma cells and melanoma-derived microvesicles.

Neoplastic cells are thought to have defective expression of costimulatory molecules. However, in this study, we show that human melanoma cells express LIGHT/TNFSF14, a ligand of herpesvirus entry mediator on T cells and of lymphotoxin beta receptor on stromal cells. In vitro, melanoma cells stained for LIGHT in the intracellular compartment, with weak or negative cell surface expression. However, LIGHT was expressed on tumor-derived microvesicles released from melanoma cells. In vivo, LIGHT was found in metastatic lesions, and the extent of lymphotoxin beta receptor expression on the stromal cells was significantly associated with a "brisk" T-cell infiltrate in the neoplastic tissue. In the lesions with a brisk T-cell infiltrate, stromal cells surrounding the tumor also stained for the T-cell attractant chemokine CCL21. The intratumoral T lymphocytes frequently expressed herpesvirus entry mediator and were characterized by a differentiated phenotype. Coculture of lymphocytes with LIGHT(+) melanoma-derived microvesicles or even with LIGHT(+) melanoma cells in the presence of interleukin-2 costimulated LIGHT-dependent CD3(+)CD8(+) T-cell proliferation. However, lymphocyte coculture with LIGHT(+) microvesicles in the presence of interleukin-2 was also associated with an apoptotic response as documented by increased binding of Annexin V by CD3(+)CD8(+) T cells. These data suggest that LIGHT constitutively expressed in human melanoma cells and microvesicles may contribute to regulate T-cell responses to tumor cells.

Apoptosis↗
PubMed2005

Reduced FEZ1/LZTS1 expression and outcome prediction in lung cancer.

Chromosomal deletions are often observed in lung cancers suggesting that inactivation of tumor suppressor genes plays an important role in the development of this neoplasm. The region around chromosome 8p22 is a frequent and early target of these deletions and has therefore been investigated for the presence of candidate genes. The FEZ1/LZTS1 gene, located at 8p22, is inactivated in many cancers with 8p deletions, including prostate, esophageal, gastric, bladder, and breast cancer and the Fez1 protein has been shown to suppress growth of cancer cells and to regulate mitosis. To elucidate the role of FEZ1 in lung cancer, we have analyzed its expression by immunohistochemistry in 103 primary lung cancer specimens including 98 non-small cell lung cancers (57 adenocarcinomas, 32 squamous cell carcinomas, 7 large cell carcinomas, and 2 others) and five small cell carcinomas. Absence of Fez1 protein expression was observed in 27 cases (26%) and additional 43 cases (42%) showed strong reduction in immunoreactivity. There was a positive association between loss of FEZ1 expression and tumor grading (P = 0.0345) and a tendency toward a reduction in the mortality rate in subjects with strong FEZ1 expression. Overall, these data indicate an important role for FEZ1 in lung cancer and suggest the possibility that it may serve as a novel prognostic indicator.

Adaptor Proteins, Signal Transducing↗
PubMed2005

Combined high-grade basal cell carcinoma and malignant melanoma of the skin ("malignant basomelanocytic tumor"): report of two cases and review of the literature.

We describe two cases of a malignant cutaneous neoplasm with combined phenotypical features of high-grade basal cell carcinoma and malignant melanoma. Some tumor cells showed a keratinocytic phenotype (cytokeratins, p63) and others a melanocytic phenotype (HMB-45, MART-1, Melan-A, S100-protein). We favor the hypothesis of a tumor with bidirectional keratinocytic and melanocytic differentiation, an exceptionally rare event.

Aged↗
PubMed2005

Undifferentiated large cell carcinoma of the thymus associated with Castleman disease-like reaction: a distinctive type of thymic neoplasm characterized by an indolent behavior.

Five cases of a distinctive type of undifferentiated large cell thymic carcinoma accompanied by an inflammatory reaction having morphologic features closely resembling those of Castleman disease (CD) of the hyaline vascular type (HVCD) are reported. The tumors occurred in 3 men and 2 women with a median age of 53 years. Three patients were asymptomatic and the tumors were found incidentally; 1 patient presented with fatigue, weight loss, dyspnea, and chest pain, and another with acanthosis nigricans. The tumors were characterized by the admixture of two components: a neoplasm of cytokeratin (+)/CD5(-) undifferentiated large tumor cells and an inflammatory reaction resembling the late stage of HVCD. Some of the cases were associated with a remarkably indolent clinical course, especially when considering their high-grade morphology. Three patients were alive without disease at 1, 10, and 22 years. One patient was alive with persistent disease at 1 year. One patient's clinical course was unique in that the primary thymic tumor was found 16 years after a metastasis had been detected in two distant lymph nodes. The two possible explanations for the coexistence here described are as follows: 1) a CD-like reaction to the tumor as the morphologic manifestation of a host immune response; and 2) a malignancy engrafted upon preexisting HVCD of the thymus, in a manner analogous to that operating in the reported cases of tumors of dendritic/reticulum cells complicating HVCD at other sites. The first hypothesis is favored, with the added suggestion that the CD-like reaction may bear a relationship to the peculiarly indolent behavior that these tumors exhibit.

Carcinoma, Large Cell↗
PubMed2004

Tissue microarray immunohistochemical expression of estrogen, progesterone, and androgen receptors in uterine leiomyomata and leiomyosarcoma.

BACKGROUND: Benign uterine leiomyomata (LMA) are hormonally responsive neoplasms. To the authors' knowledge, little is known regarding the hormonal expression patterns of leiomyosarcomas (LMSs) of the uterus. The objective of the current study was to assess the immunohistochemical (IHC) patterns of estrogen receptor (ER), progesterone receptor (PR), and androgen receptor (AR) expression in LMA and LMS of the uterus using a tissue microarray. The authors also sought to assess the prognostic value of ER, PR, and AR expression in LMS. METHODS: Between January 1991 and March 2001, 25 patients were identified with primary uterine LMS for whom tissue was available. A tissue microarray was created with 3 representative cores from each of the LMS cases, as well as from 19 cases with benign uterine LMA. IHC staining was scored as follows: negative (0-1) and positive (2-3). Outcome analyses were performed for LMS only. First recurrence was determined from the time of the initial diagnosis. Survival was determined from the time of the initial diagnosis to last follow-up. RESULTS: ER, PR, and AR positivity in LMA compared with LMS was as follows: ER, 78% versus 40% (P = 0.03); PR, 88% versus 38% (P = 0.001); and AR, 32% versus 40% (P = 0.75). There was no difference noted with regard to IHC expression based on stage of LMS. The median overall survival for patients with LMS was 23.5 months (95% confidence interval, 19.5, NR). When adjusted for stage, PR and AR were found to be predictive of a lower risk of recurrence (P = 0.01 and P = 0.035, respectively). ER, PR, and AR were not found to be associated with overall survival after adjustment for stage. Tumor stage was found to be associated with survival (P = 0.005). CONCLUSIONS: The rate of ER and PR expression was found to be significantly less in uterine LMS compared with LMA. ER, PR, and AR expression was observed in approximately 30-40% of uterine LMS cases. In the current series, PR and AR expression appeared to be associated with disease-free survival but were not found to correlate with overall survival.

Adult↗
PubMed2004

Congenital fibrosarcoma with metastasis in a fetus.

It is well known that congenital or infantile fibrosarcoma has a much less aggressive behavior than fibrosarcoma in adults, and it rarely metastasizes. We report a case of congenital fibrosarcoma in a 26-wk-old fetus, the diagnosis of which was made by an in utero needle core biopsy. Metastatic tumors were identified at autopsy when the pregnancy was terminated 3 wk later. English literature of metastatic congenital fibrosarcoma was also reviewed.

Adrenal Gland Neoplasms↗
PubMed2004

Cylindroma of the breast of skin adnexal type: a study of 4 cases.

Four cases of solitary cylindroma of the breast of skin adnexal type are described. The tumors were morphologically and immunophenotypically identical to their dermal counterparts. They arose in close proximity to the nipple, such as the retroareolar area of the breast and in intimate association with the lactiferous ducts, suggesting an origin from the latter structures. One case occurred in a woman with hereditary multiple cylindromatosis (Brooke-Spiegler syndrome). This is the second reported case of this hereditary syndrome with extracutaneous manifestations and the first case in which the breast is involved.

Adult↗
PubMed2004

Thymic mucoepidermoid carcinomas: a clinicopathologic study of 10 cases and review of the literature.

BACKGROUND: Primary thymic carcinomas are rare malignant neoplasms, of which at least 10 different histologic variants have been described. Among these variants, thymic mucoepidermoid carcinomas morphologically similar to the homonymous salivary gland counterparts are particularly unusual; only 9 cases for which clinicopathologic features were available have been reported. OBJECTIVE: To study the clinicopathologic features of primary thymic mucoepidermoid carcinoma in an effort to better define their histologic features and biologic behavior. DESIGN: The clinical and pathologic features of 10 cases of thymic mucoepidermoid carcinoma were reviewed and compared with those of previously reported cases. RESULTS: The patients ranged in age from 8 to 84 years (mean 49 years), with 6 men and 4 women. The initial manifestations included respiratory symptoms and weight loss. Some patients were asymptomatic. All tumors were located adjacent to residual benign thymic tissue, and 3 cases were associated with multilocular thymic cysts. Histologically, the tumors consisted of sheets, lobules and nests of squamous, mucinous and intermediate cells in densely fibrotic stroma. There were 8 low-grade cases and 2 high-grade cases. The 2 patients with high-grade tumors died 1 year after diagnosis, whereas all but 1 patient with low-grade tumors in which follow-up was available were found to be alive and well on follow-up examination. One patient with low-grade tumor but high-stage disease died after developing a local recurrence. Among the 9 cases reported in the literature, 4 cases resulted in fatal outcomes; 2 cases were high-stage disease and 2 were high-grade tumors. CONCLUSIONS: Thymic mucoepidermoid carcinomas are predominantly low-grade tumors, and may be associated with multilocular thymic cysts. Poor prognosis is related to high-grade histology and high-stage disease.

Adolescent↗
PubMed2002

Pseudallescheriasis as an aggressive opportunistic infection in a bone marrow transplant recipient.

Pseudallescheria boydii is a low-virulence fungus that is the main causative agent of posttraumatic mycetoma in a nonimmunocompromised host. Immunocompromised patients are at high risk for locally invasive or disseminated Pseudallescheria infection. However, aggressive opportunistic infections due to P boydii are reported infrequently because it morphologically resembles other fungi, especially Aspergillus species, on tissue histology; therefore, such infections are not identified and treated properly. We report a case of disseminated P boydii infection in a patient following bone marrow transplantation. The identity of the fungus was not recognized until microbiologic culture results became available. Our case illustrates the importance of recognizing this fungus as an opportunistic infection in immunocompromised patients, as well as the need for culture of biopsy material for proper identification so that appropriate therapy can be instituted.

Bone Marrow Transplantation↗