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Toshiaki Saida

Publications and source records attributed to Toshiaki Saida.

At least 19 recordsLinked to original sources
PubMed2005

Intratumoral injection of immature dendritic cells enhances antitumor effect of hyperthermia using magnetic nanoparticles.

Dendritic cells (DCs) are potent antigen-presenting cells that play a pivotal role in regulating immune responses in cancer and have recently been shown to be activated by heat shock proteins (HSPs). We previously reported that HSP70 expression after hyperthermia induces antitumor immunity. Our hyperthermia system using magnetite cationic liposomes (MCLs) induced necrotic cell death that was correlated with HSP70 release. In the present study, we investigated the therapeutic effects of DC therapy combined with MCL-induced hyperthermia on mouse melanoma. In an in vitro study, when immature DCs were pulsed with mouse B16 melanoma cells heated at 43 degrees C, major histocompatibility complex (MHC) class I/II, costimulatory molecules CD80/CD86 and CCR7 in the DCs were upregulated, thus resulting in DC maturation. C57BL/6 mice bearing a melanoma nodule were subjected to combination therapy using hyperthermia and DC immunotherapy in vivo by means of tumor-specific hyperthermia using MCLs and directly injected immature DCs. Mice were divided into 4 groups: group I (control), group II (hyperthermia), group III (DC therapy) and group IV (hyperthermia + DC therapy). Complete regression of tumors was observed in 60% of mice in group IV, while no tumor regression was seen among mice in the other groups. Increased cytotoxic T lymphocyte (CTL) and natural killer (NK) activity was observed on in vitro cytotoxicity assay using splenocytes in the cured mice treated with combination therapy, and the cured mice rejected a second challenge of B16 melanoma cells. This study has important implications for the application of MCL-induced hyperthermia plus DC therapy in patients with advanced malignancies as a novel cancer therapy.

Animals↗
PubMed2005

Anatomical and histopathological correlates of the dermoscopic patterns seen in melanocytic nevi on the sole: a retrospective study.

BACKGROUND: Anatomical and histopathologic correlates of the unique dermoscopic patterns seen in melanocytic nevi on acral volar skin is yet to be clarified. OBJECTIVE: Our aim was to investigate the relation between the dermoscopic patterns and anatomical and histopathological characteristics of melanocytic nevi on the sole. METHODS: The precise locations of 298 melanocytic nevi on the sole from 278 patients were retrospectively investigated, with attention paid to each dermoscopic pattern. In addition, 35 nevi showing each typical dermoscopic pattern were excised and evaluated histopathologically. RESULTS: Melanocytic nevi showing the parallel furrow pattern or the fibrillar pattern were located on the portions of the sole with regular parallel skin markings and were not found on the arch areas of the foot. Moreover, a subtle but distinctive difference in the distribution was observed between nevi of the two patterns; the nevi with the fibrillar pattern showed a tendency for the sites directly pressed by the body's weight. Melanocytic nevi of the lattice-like pattern were mostly located on the arch areas. Histopathologically, irrespective of the dermoscopic patterns, nests of nevus cells were mainly located in the epidermal rete ridges underlying the surface sulci. In the nevi with a fibrillar pattern, the cornified layer showed a slanting arrangement, which is considered to be a histopathological background of the fibrillar pattern. CONCLUSION: Dermoscopic patterns seen in acral melanocytic nevi could be explained by the unique anatomical and histopathological characteristics of the acral skin.

Adolescent↗
PubMed2004

Significance of dermoscopic patterns in detecting malignant melanoma on acral volar skin: results of a multicenter study in Japan.

OBJECTIVE: To determine diagnostic variables such as sensitivity and specificity of the major dermoscopic patterns observed in melanocytic lesions on acral volar skin, with particular attention to the significance of the parallel ridge pattern and irregular diffuse pigmentation in detecting acral melanoma. DESIGN: Multicenter, retrospective study. SETTING: University hospitals in Japan. PATIENTS: Patients with melanocytic lesions on acral volar skin. A total of 712 melanocytic lesions (103 malignant melanomas, including 36 in situ lesions, and 609 melanocytic nevi) were consecutively collected from the files of 3 hospitals. Diagnoses of all the lesions had been determined histopathologically. INTERVENTIONS: Dermoscopic examination. MAIN OUTCOME MEASURES: The sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of the major dermoscopic patterns seen in benign and malignant melanocytic lesions on acral volar skin. RESULTS: The parallel ridge pattern and irregular diffuse pigmentation showed extremely high specificity (99.0% and 96.6%, respectively) and very high negative predictive value (97.7% and 97.5%, respectively) in malignant melanoma. For melanoma in situ, the positive predictive value and diagnostic accuracy of the parallel ridge pattern were significantly higher than those of irregular diffuse pigmentation (P = .009 and P = .006, respectively). In melanocytic nevi, the specificity and positive predictive value of the parallel furrow pattern and/or the latticelike pattern were found to be very high (93.2% and 98.3%, respectively). CONCLUSIONS: Dermoscopy is immensely helpful in differentiating malignant melanomas from melanocytic nevi on acral volar skin. Moreover, the parallel ridge pattern aids in detecting acral melanomas in early, curable stages.

Adult↗
PubMed2004

Number of acquired melanocytic nevi in patients with melanoma and control subjects in Japan: Nevus count is a significant risk factor for nonacral melanoma but not for acral melanoma.

BACKGROUND: Epidemiologic studies have suggested that number of acquired melanocytic nevi is a risk factor for melanoma development in Japanese as it is in white populations. However, there are only a few population-based studies on acquired nevi in Asian populations, and no epidemiologic study on relationship between number of acquired nevi and melanoma in Japanese populations has been reported. OBJECTIVE: The purpose of this study was to assess number, size, and distribution of acquired melanocytic nevi in a Japanese population. Particular attention was paid to evaluation of relationship between number of acquired nevi and development of nonacral or acral malignant melanoma. METHODS: In all, 82 patients with malignant melanoma and 600 control subjects were included in this study. All participants were Japanese. The number of acquired melanocytic nevi, 2 mm or larger in diameter, on the whole body except the scalp and genital areas was counted by experienced dermatologists. The participants were divided into 5 age categories (0-19, 20-39, 40-59, 60-79, and >80 years old) for the statistical analyses. This categorization adjusted the age and sex distribution between patients with melanomas and control subjects in 40- to 59-, 60- to 79-, and over 80-year-old groups. RESULTS: In the control Japanese population, the number of acquired melanocytic nevi on the whole body increased with age in 0- to 19-year-old age group and reached the highest number, 6.7 +/- 8.1/person, in 20- to 39-year-old group. In patients with nonacral melanoma, the number of acquired nevi on the whole body in 40- to 59- and 60- to 79-year-old groups was significantly higher than that of the corresponding control group. In contrast, the rate of individuals who had acquired nevi on soles, palms, and nail apparatus was not significantly different between acral melanoma group and the control group in 40- to 59- and 60- to 79-year-old groups. CONCLUSION: This study has revealed that a large number of acquired melanocytic nevi is a risk factor for the development of nonacral melanoma in Japanese and white populations. However, acquired nevi on soles, palms, and nail apparatus do not seem to be a risk factor for acral melanoma in Japanese populations.

Adult↗
PubMed2004

Histopathological characteristics of malignant melanoma affecting mucous membranes: a unifying concept of histogenesis.

AIMS: To investigate histopathological characteristics of melanocytic lesions affecting mucous membranes in various anatomical sites. Particular attention was paid to elucidation of morphological characteristics of early phases of mucosal melanoma in order to contribute to effective detection of this highly malignant neoplasm in the curable stages. METHODS: A total of 87 melanocytic lesions of mucous membranes were investigated histopathologically. There were 55 malignant melanomas including eight lesions of melanoma in situ, three in the radial growth phase (RGP) and 44 in the vertical growth phase (VGP), and 28 benign melanocytic lesions including four melanotic macules, 19 melanocytic naevi and five blue naevi. In addition, this series also included four equivocal lesions for which diagnoses were not definitely determined. With regard to malignant melanoma, histopathological patterns of in situ phase and RGP were intensely evaluated. RESULTS: Histopathological features of benign melanocytic lesions were essentially the same as those of the corresponding lesions of the skin. In the vast majority of mucosal melanomas, irrespective of anatomical sites, the main histopathological pattern seen in melanoma in situ and in RGP was the lentiginous pattern, which shows proliferation of atypical melanocytes in the lower layer of more or less acanthotic epithelium, though subtle variations of the pattern were detected. No association of melanocytic naevus was detected in any cases of melanoma. Based on these findings, we have proposed a unifying concept of de novo histogenesis of mucosal malignant melanoma. CONCLUSIONS: Our concept of histogenesis of mucosal melanoma assists in the identification of this highly malignant neoplasm in the early curable stages.

Diagnosis, Differential↗
PubMed2004

Skin infiltration of juvenile myelomonocytic leukemia.

We described a two-year-old boy who developed a skin infiltration from JMML. Several indurated erythematous lesions were seen on his back on his first visit to our department. Edematous erythemas had repeatedly appeared on his auricles and feet for the previous six months. He had had a high fever for a month. Hepatosplenomegaly and superficial lymphadenopathy were recognized. Laboratory investigation showed leukocytosis and anemia. The diagnosis of JMML was confirmed by the findings of myeloid hyperplasia in his bone marrow and the spontaneous colony formation and GM-CSF hypersensitivity in a culture of bone marrow cells. Histopathologically, large atypical mononuclear cells were infiltrated throughout the dermis in a perivascular and interstitial distribution in a skin biopsy specimen. These cells were CD3 (-), CD20 (-), CD45 (+), CD68 (+) and myeloperoxidase (+). Bone marrow transplantation and then cord blood stem cell transplantation were performed but soon rejected. The indurated erythematous lesions appeared again soon after the relapse of JMML. There are other reported cases of JMML with skin infiltration that preceded any other manifestations of the disease. JMML cells in some patients, including our case, seem to have a great affinity for the skin, and skin biopsy aids in early detection of this disease.

Back↗
PubMed2004

Diagnosis and categorization of acral melanocytic lesions using teledermoscopy.

We performed a multicentre study to test the validity of teledermoscopy for diagnosing acral melanoma and to evaluate inter-observer agreement on the classification of acral melanocytic lesions. Dermoscopic images of 77 acral melanocytic lesions (71 common melanocytic naevi and 6 melanomas) were sent by email to 11 dermatologists with different degrees of experience in dermoscopy. The observers analysed the images on a computer monitor to diagnose acral melanoma or atypical lesions and to categorize all lesions. All 11 observers, regardless of their degree of experience, obtained high values for sensitivity (mean 0.91, SD 0.09) and specificity (mean 0.95, SD 0.04) with regard to the diagnosis of melanoma. The inter-observer agreement was good to excellent (kappa 0.49-0.88) for the categorization of acral melanocytic lesions. All six melanomas were correctly classified as 'atypical pattern' and all observers recommended surgical excision. Teledermoscopy represents a useful tool for the diagnosis of acral melanoma and for the categorization of patterns that suggest benign or potentially malignant acral melanocytic lesions.

Adolescent↗
PubMed2004

[Angiosarcoma].

Angiosarcoma is a malignant neoplasm of endothelial cells. It is a fatal disease because of the high potentiality of hematogeneous metastasis. Although a definitively effective treatment has not yet established, a rational combination of multimodal therapies could prolong the survival time to some extent. In this review, recent advances in the management of this neoplasm are discussed, including those in surgery, radiation, chemotherapy and biotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2003

ASC/TMS1, a caspase-1 activating adaptor, is downregulated by aberrant methylation in human melanoma.

ASC/TMS1 is an adaptor protein activating caspase-1 that stimulates processing of proIL-1beta and proIL-18. ASC was reported to be aberrantly methylated and silenced in human breast cancers. In our present study, ASC expression was examined in 12 melanoma cell lines by Western blot analysis and in 18 benign melanocytic nevi and 32 melanoma tissues by immunohistochemical staining. ASC expression was absent or reduced in 7 of 12 (58.3%) cell lines and in 20 of 32 (62.5%) melanoma tissues, whereas all 18 benign melanocytic nevi showed intensive ASC expression. To investigate whether ASC silencing in melanoma is involved in aberrant methylation, methylation specific PCR was carried out. Five of ten (50%) melanoma tissues exhibited methylation in CpG island of ASC companied with reduced ASC expression. Six of twelve (50%) melanoma cell lines showed aberrant methylation in the ASC gene, and 4 of the 6 (66.7%) methylation positive cell lines exhibited reduced ASC expression. We characterized methylation patterns in melanoma cell lines by using bisulfite genomic sequencing, and found that the degree of aberrant methylation correlated with the level of reductive ASC expression. Treatment with demethylating agent 5-aza-2'-deoxycytidine resulted in both demethylation of the ASC gene and the upregulation of ASC expression in the methylation positive melanoma cell lines. Our study shows that ASC is downregulated in melanoma, and that its suppression is partially mediated by aberrant methylation.

Apoptosis↗
PubMed2003

The place of lymphatic mapping and sentinel node biopsy in oncology.

The techniques of sentinel lymphatic mapping (LM) and sentinel lymph node biopsy (SLNB) have become almost routine for the staging of clinically node-negative patients with high-risk cutaneous melanoma. The techniques are also widely applied to staging of the axilla in breast cancer. Investigations of the use of LM and SLNB for other solid malignancies have also shown promise. LM/SLNB requires a multidisciplinary effort involving experienced surgeons, nuclear medicine physicians, and surgical pathologists. The techniques require a learning curve for all involved personnel, requiring experience with at least 30 cases followed by complete nodal dissection after SLNB to achieve full competency. Surgical pathologists play a pivotal role in determining optimum sentinel node analysis. The techniques have lower morbidity and greater accuracy than traditional complete regional node dissection. Pathologists are receiving increasing numbers of SLN specimens and are expected to evaluate the results of the application of the LM/SLNB techniques to a range of solid tumors. We have reviewed LM/SLNB in regard to melanoma and breast cancer and other types of malignancies. The techniques have much to offer, but despite their seeming simplicity, need considerable technical skill and clinical judgment if they are to be effectively applied. They also provide unique opportunities for basic and translational research.

Breast Neoplasms↗
PubMed2003

Nonpigmenting solitary fixed drug eruption caused by a Chinese traditional herbal medicine, ma huang (Ephedra Hebra), mainly containing pseudoephedrine and ephedrine.

We describe a case of nonpigmenting solitary fixed drug eruption appearing on the right thigh of a 31-year-old woman in Japan. The causative drug was determined by closed patch test on postlesional skin as a Chinese traditional herbal medicine, ma huang (Ephedra Hebra), mainly containing pseudoephedrine and ephedrine.

Adult↗
PubMed2003

Dermoscopy of pigmented skin lesions: results of a consensus meeting via the Internet.

BACKGROUND: There is a need for better standardization of the dermoscopic terminology in assessing pigmented skin lesions. OBJECTIVE: The virtual Consensus Net Meeting on Dermoscopy was organized to investigate reproducibility and validity of the various features and diagnostic algorithms. METHODS: Dermoscopic images of 108 lesions were evaluated via the Internet by 40 experienced dermoscopists using a 2-step diagnostic procedure. The first-step algorithm distinguished melanocytic versus nonmelanocytic lesions. The second step in the diagnostic procedure used 4 algorithms (pattern analysis, ABCD rule, Menzies method, and 7-point checklist) to distinguish melanoma versus benign melanocytic lesions. kappa Values, log odds ratios, sensitivity, specificity, and positive likelihood ratios were estimated for all diagnostic algorithms and dermoscopic features. RESULTS: Interobserver agreement was fair to good for all diagnostic methods, but it was poor for the majority of dermoscopic criteria. Intraobserver agreement was good to excellent for all algorithms and features considered. Pattern analysis allowed the best diagnostic performance (positive likelihood ratio: 5.1), whereas alternative algorithms revealed comparable sensitivity but less specificity. Interobserver agreement on management decisions made by dermoscopy was fairly good (mean kappa value: 0.53). CONCLUSION: The virtual Consensus Net Meeting on Dermoscopy represents a valid tool for better standardization of the dermoscopic terminology and, moreover, opens up a new territory for diagnosing and managing pigmented skin lesions.

Algorithms↗
PubMed2003

Growth inhibition of subcutaneous mouse melanoma and induction of natural killer cells by liposome-mediated interferon-beta gene therapy.

In this study we investigated the antitumour effect and mechanism of action of cationic liposome-mediated murine interferon-beta (IFNbeta) gene therapy in mouse B16F1 melanoma cells in vitro and in vivo. Murine IFNbeta gene transfer by cationic liposome resulted in substantial growth inhibition of B16F1 melanoma cells in culture when compared with phosphate buffered saline or recombinant murine IFNbeta treatment, or lacZ control gene transfer. Use of video-enhanced contrast-differential interference contrast (VEC-DIC) microscopy revealed that liposomes containing the murine IFNbeta gene [lip(pSV2muIFNbeta)], but not recombinant murine IFNbeta, induced dramatic morphological changes that characterize apoptosis, including bleb formation, shrinkage of cells, nuclear condensation and 'ballooning', in approximately 30% of the cells treated. Intratumoral administration of lip(pSV2muIFNbeta) resulted in a 5.5-fold reduction in the mean volume of subcutaneous melanoma lesions in syngeneic mice 15 days after treatment and eradicated the tumour in 18% of the mice treated. Immunocytochemical analysis demonstrated that a larger number of natural killer (NK) cells infiltrated the tumour following lip(pSV2muIFNbeta) treatment than in controls. In vivo depletion of NK cells using the anti-asialoGM1 antibody reduced the efficacy of lip(pSV2muIFNbeta) treatment. Taken together, our data suggest that cationic liposome-mediated IFNbeta gene therapy could be effective against melanoma by directly inducing cell death and stimulating NK cells.

Animals↗
PubMed2003

Results of a phase I clinical study using autologous tumour lysate-pulsed monocyte-derived mature dendritic cell vaccinations for stage IV malignant melanoma patients combined with low dose interleukin-2.

We conducted a pilot study to assess the feasibility and efficacy of immunotherapy for stage IV malignant melanoma patients resistant to conventional therapies involving vaccination with mature dendritic cells (mDCs) combined with administration of low dose interleukin-2. Autologous monocytes were harvested from a single apheresis and cultured for 7 days with granulocyte-macrophage colony-stimulating factor and interleukin-4, yielding immature dendritic cells (iDCs), which were then cryopreserved until use. For 4 days prior to vaccination, iDCs were exposed to autologous tumour lysate combined with tumour necrosis factor-alpha to induce terminal differentiation into mDCs. Patients were then vaccinated weekly with 107 mDCs for 10 weeks and given 350-700 kIU of interleukin-2 three times per week. Of the 10 patients in the study, one showed stable disease, seven showed progressive disease, and two showed mixed responses, including partial tumour regression, and were therefore given 20 additional injections. Only minimal adverse events were noted, including localized skin reactions and mild fever (NIH-CTC grade 0-1). Median survival from the first vaccination was 240 days (range 31-735 days). In vitro, melanoma patient-derived dendritic cells (DCs) showed reduced cell surface expression of CD1a antigen on iDCs and reduced CD86 and HLA-DR expression on mDCs. In addition, antigen uptake, chemotaxis and antigen presentation were all attenuated in DCs from the patients. In summary, although improvement of clinical efficacy will require further research, autologous tumour lysate-pulsed monocyte-derived mDCs could be safely harvested, cryopreserved and administrated to patients without obvious complications.

Adult↗
PubMed2003

Tumor regression by combined immunotherapy and hyperthermia using magnetic nanoparticles in an experimental subcutaneous murine melanoma.

Immunotherapy (IT) has become an accepted therapeutic modality. We previously reported that intracellular hyperthermia (IH) using magnetic nanoparticles induces antitumor immunity. We undertook these studies in order to study the combined effects of IT and IH on melanoma. Magnetite cationic liposomes (MCLs) have a positive surface charge and generate heat in an alternating magnetic field (AMF) due to hysteresis loss. MCLs were injected into a B16 melanoma nodule in C57BL/6 mice, which were subjected to AMF for 30 min. The temperature at the tumor reached 43 degrees C and was maintained by controlling the magnetic field intensity. At 24 h after IH, interleukin-2 (IL-2) or granulocyte macrophage-colony stimulating factor (GM-CSF) was injected directly into the melanoma. Mice were divided into six groups: group I (control), group II (IH), group III (IL-2), group IV (GM-CSF), group V (IH + IL-2), and group VI (IH + GM-CSF). Complete regression of tumors was observed in mice of groups V and VI (75% (6/8) and 40% (4/10) of the mice, respectively), while no tumor regression was observed in mice of the other groups. This study supports the combined use of IT and IH using MCLs in patients with advanced malignancies.

Animals↗