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Yasuhiro FUJISAWA, Akifumi YAMAMOTO, Hiroaki IWATA, Akira TAKAHASHI, N ...
2004 Volume 19 Issue 1 Pages
7-15
Published: March 31, 2004
Released on J-STAGE: August 05, 2010
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Dendritic cells (DC) are professional antigen-presenting cells specialized to initiate and regulate T-cell immune responses. Many clinical trials using antigen-pulsed DC have been reported recently. We performed a phase I clinical vaccination trial on melanoma patients using peptide-pulsed DC and observed clinical and immunological responses consisting of anti-tumor responses in 2 patients and significant expansion of antigen specific cytotoxic T lymphocytes in the peripheral blood lymphocytes of 1 patient. Our data indicate that the vaccination of peptide-pulsed DC is capable of inducing clinical and systemic tumor-specific immune responses. But the clinical response was not satisfactory, indicating that a variety of immune escape mechanisms are operative at the tumor site and have to be overcome for successful vaccination. [
Skin Cancer (Japan) 2004; 19: 7-15]
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Naotaka SHIBAGAKI
2004 Volume 19 Issue 1 Pages
16-24
Published: March 31, 2004
Released on J-STAGE: August 05, 2010
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Recently, we have begun to explore the utility of bacterial recombinant proteins that bear protein transduction domains (PTDs) as a component of dendritic cell-based cancer vaccine strategies.
PTDs are short stretches of positively charged amino acids that enable to proteins that contain them to efficiently enter cells in an energy- and receptor-independent fashion. We have incorporated the HIV TAT protein PTD into recombinant proteins and demonstrated that these proteins transduce dendritic cells very efficiently. We have also demonstrated that transduction of mouse dendritic cells with recombinant PTD-containing antigens empowers them with the ability to elicit CTL response against non-self antigens. The CTL activity generated is sufficient to prevent engraftment of mice with tumors, and these vaccines have some theoretical advantages over those that are in current use, and may potentially be useful in patients. [
Skin Cancer (Japan) 2004; 19: 16-24]
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Yutaka KAWAKAMI
2004 Volume 19 Issue 1 Pages
25-33
Published: March 31, 2004
Released on J-STAGE: August 05, 2010
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Identification of human melanoma antigens by various molecular biological and immunological techniques and evaluation of tumor reactive T cells in patients with the identified tumor antigen and HLA tetramer technology revealed several basic problems involved in immunological tumor rejection, including inhibitory environment in local tumor tissues and the induction of regulatory T cell. However, the recently improved immunotherapy, based on the results from this basic and clinical research, including active immunization with modified antigen peptides and recombinant virus, T cell adoptive transfer with lymphodepletive pretreatment, and administration of anti-CTLA-4 Ab, demonstrated better anti-tumor effects. Further improvement of immunotherapy is expected for patients with melanoma. [
Skin Cancer (Japan) 2004; 19: 25-33]
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Toshiro KAGESHITA
2004 Volume 19 Issue 1 Pages
34-40
Published: March 31, 2004
Released on J-STAGE: August 05, 2010
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Recent progress in molecular genetics and improvement in the understanding of immune responses to tumors have generated an interest in using gene-based therapy for the treatment of cancers. Several basic strategies have emerged so far but one of the most popular approaches currently under development is immuno-gene therapy. Since melanomas are often immunogenic and salient aspects of their immunology are known, malignant melanoma is a promising target for immuno-gene therapy.
This article reviews the published gene transfer studies and summarizes the most recent data of clinical trials of gene therapy for patients with melanoma.
Clinical trials in the US and European countries have shown the feasibility and safety of gene therapy against melanoma. Although no major successes have been reported, positive results, which include the enhancements of systemic anti-tumor cellular and/or humoral responses, have been observed in some patients. These data support the potential of gene therapy in the management of melanoma. Better vector technology, including
in vivo delivery and targeting, as well as coping with immunological escape phenomena would provide the tools to validate gene therapy as an effective modality of treatment for malignant melanoma. [
Skin Cancer (Japan) 2004; 19: 34-40]
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Toshiaki SAIDA, Kazuhiko MATSUMOTO, Toshiro KAGESHITA, Masaaki MIZUNO, ...
2004 Volume 19 Issue 1 Pages
41-47
Published: March 31, 2004
Released on J-STAGE: August 05, 2010
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Results of our basic research for the development of gene therapy by means of cationic liposomes were reviewed.
In vitro and
in vivo studies have revealed that repeated exposure of melanoma cells to the liposomes containing interferon-β gene increased the number of transfected cells with the gene and induced substantial expression of IFN-β. In the system of B6 mice/16 mouse melanoma, growth of melanoma nodules was significantly suppressed with a single injection of IFN-β gene (3μg DNA). Moreover, human melanoma nodules transplanted to the nude mice completely regressed after 6 times of injection of the liposomes containing IFN-β gene (3μg DNA). Immunohistochemical investigation revealed degenerative changes of melanoma cells corresponding to apoptosis. These data give a solid base for the clinical application of this gene therapy to malignant melanoma. The protocol of the clinical trial was evaluated and has been approved by the Working Committee of the Ministry of Health, Labour, and Welfare. The phase I/II clinical study will soon start. [
Skin Cancer (Japan) 2004; 19: 41-47]
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Hiroaki YAGI
2004 Volume 19 Issue 1 Pages
48-54
Published: March 31, 2004
Released on J-STAGE: August 05, 2010
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Treatments should be based on reviews of the best available evidence. Evidence-based medicine has its own clear hierarchy with systematic reviews of randomized controlled trials at the top level and expert and user opinion at the lowest level of evidence. Topical application of corticosteroids and ACNU, PUVA, narrow- or broad-band UVB, interferon-γ, local or total skin electron beam irradiation, retinoids and combination chemotherapy are available in the treatment of cutaneous T-cell lymphoma (CTCL) . Sole or combinations of several methods should be appropriately used depending on the staging, prognosis and complications of the disease and performance status of the patient. However, very few randomized controlled trials are reported in the treatment of CTCL. This article reviews the evidence of each treatment based on the highest quality studies available. [
Skin Cancer (Japan) 2004; 19: 48-54]
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Shinichiro TSUMORI, Mitsuru SETOYAMA
2004 Volume 19 Issue 1 Pages
55-63
Published: March 31, 2004
Released on J-STAGE: August 05, 2010
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Cutaneous malignant lymphomas are a heterogeneous group and show an indolent to a very aggressive course. Accordingly, therapeutic goals are various.
We reviewed chemotherapies, including CHOP and supportive care, for cutaneous lymphoma based on current evidence. [
Skin Cancer (Japan) 2004; 19: 55-63]
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Kazuhiro KAWAI
2004 Volume 19 Issue 1 Pages
64-71
Published: March 31, 2004
Released on J-STAGE: August 05, 2010
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To assess the evidence for the efficacy of salvage therapy for chemorefractory or relapsed mycosis fungoides (MF)/Sézary syndrome (SS), a review of MEDLINE search was performed. Treatment recommendations cannot be made for chemorefractory or relapsed MF/SS, because no randomized controlled trial was identified. Small phase II trials have shown the effectiveness of EPOCH chemotherapy, pentostatin, pentostatin + IFN-α-2a, fludarabine + IFN-α-2a, cladribine, and gemcitabine in patients with chemorefractory or relapsed MF/SS, but no survival benefit has been established for any treatment modality because of the short duration of responses. A few case reports and small case series have been published on the effect of hematopoietic stem cell transplantation (HSCT) in MF/SS. Although most patients treated with autologous HSCT and high-dose chemotherapy achieved CR, the responses were generally short-lived. In contrast, allogeneic HSCT has been described with evidence of long-lasting remissions in patients with advanced MF/SS. Thus, allogeneic HSCT including reduced intensity regimen (mini-transplantation) may cure MF/SS, although there is a need for further validation. [
Skin Cancer (Japan) 2004; 19: 64-71]
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Mikio OHTSUKA
2004 Volume 19 Issue 1 Pages
72-79
Published: March 31, 2004
Released on J-STAGE: August 05, 2010
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In this report, a role of radiation therapy in the management of primary cutaneous lymphoma was reviewed. There is no randomized trial to evaluate the efficacy of treatment modalities for primary cutaneous lymphoma except one, which compares combination radiation and chemotherapy with topical therapy in the initial treatment of mycosis fungoides. Most of the articles referring to treatment outcomes were descriptive studies. Well-designed controlled studies may be required to establish the significance of radiation therapy for cutaneous lymphoma. [
Skin Cancer (Japan) 2004; 19: 72-79]
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Takahiro KIYOHARA
2004 Volume 19 Issue 1 Pages
80-89
Published: March 31, 2004
Released on J-STAGE: August 05, 2010
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Rituximab is a chimeric anti-CD20 monoclonal antibody containing human IgGl and κ constant regions with murine variable regions. The anti-lymphoma effects are due to complement and anti-body-dependent cell-mediated cytotoxicity, and induction of apoptosis. The safety and efficacy of rituximab in combination with CHOP chemotherapy (R-CHOP) have been demonstrated in the treatment of follicular and diffuse large B-cell lymphoma. Since rituximab combined with cytosine arabinoside brings an excellent effect of purging in relapsed or refractory follicular lymphoma, this combination is expected to be a good method for
in vivo purging in auto-peripheral blood stem cell transplants.
Ibritumomab tiuxetan has an excellent anti-lymphoma profile, and it appears to have higher response rates than rituximab. It is expected to be effective for bulky masses in follicular lymphoma.
We here examine the efficacy and possibility of anti-CD20 monoclonal therapy for the patients with cutaneous B-cell lymphoma. [
Skin Cancer (Japan) 2004; 19: 80-89]
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Mitsuru SETOYAMA
2004 Volume 19 Issue 1 Pages
90-95
Published: March 31, 2004
Released on J-STAGE: August 05, 2010
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Primary cutaneous lymphomas represent distinct clinical and histopathologic subtypes of extranodal T-and B-cell lymphomas. The EORTC classification for primary cutaneous lymphomas proposed in 1997, is based on a combination of clinical, histologic, and immunophenotypic criteria. Thus, the classification may be useful for dermatological clinicians to plan treatments. On the other hand, new WHO classification is not an organ-based classification, and some categories include both cutaneous and systemic diseases, and these may have very different prognoses. However, pathologists will try to utilize the WHO classification, and to unify diagnoses for further clinical and scientific research. The review discusses problematical areas in both WHO and EORTC classifications. [
Skin Cancer (Japan) 2004; 19: 90-95]
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Naoya YAMAZAKI
2004 Volume 19 Issue 1 Pages
96-102
Published: March 31, 2004
Released on J-STAGE: August 05, 2010
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The sentinel node biopsy technique was first described by Morton and Cochran et al., who confirmed by clinical experience the biological hypothesis that the pathological findings of the sentinel node reflects the entire situation of all the other nodes of the regional lymph node basin.
At the Division of Dermatology, National Cancer Center Hospital, intraoperative lymphatic mapping and sentinel node biopsy were performed by intradermal injection of blue dye in 49 cases, and performed by injection of technetium tin colloid plus blue dye in 12 cases of cutaneous malignant melanoma. The sensitivity and accuracy of our study were similar to those reported in another first series, and our study demonstrated that the technique of lymphatic mapping and sentinel node biopsy were both sensitive and specific.
Although it was an initial experience at the National Cancer Center Hospital, sentinel node biopsy proved feasible and successful. [
Skin Cancer (Japan) 2004; 19: 96-102]
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Eriko KUSANO, Sumino ABE, Reiko TAKIMOTO, Kenji TAKAMORI
2004 Volume 19 Issue 1 Pages
103-106
Published: March 31, 2004
Released on J-STAGE: August 05, 2010
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A 78-year-old man was referred to our dermatology department for two dusky red plaques on the forehead. The patient was diagnosed with cutaneous angiosarcoma of the scalp on the basis of histological criteria, and surgical excision of a large area was performed with local injection of rIL-2. But a relapse occurred 3 months later. Therefore the patient received electron beam therapy (68 grays) leading to a decrease of the cutaneous lesion. 50 days later, pneumothorax occurred with local recurrences and metastases to the neck skin and cervical nodes occurred. The patient died as a result of respiratory failure 381 days after the first medical examination. Postmortem examination revealed multiple metastases of the both lungs, diaphragm and liver. These findings suggest that IL-2 therapy and radiation therapy were of limited efficacy in the treatment of angiosarcoma of the scalp. [
Skin Cancer (Japan) 2004; 19: 103-106]
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Kana HIOKI, Tomoko IZUMI, Miki NAGAI, Hideki KAMIYA, Yasuo KITAJIMA
2004 Volume 19 Issue 1 Pages
107-111
Published: March 31, 2004
Released on J-STAGE: August 05, 2010
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We reported a case of angiosarcoma in a 68-year-old man. The patient had noticed some subcutaneous nodules on the left side of his forehead during the previous two years. Although, he was treated first with radiotherapy and IL-2 therapy, metastasis to the left cervical lymph node and the lungs were developed one year later. For the treatment of the metastasis, we performed intravenous Pacritaxel injection concurrent with radiation and local injection of IL-2. Pacritaxel 55mg/m
2 was administrated 3 times at six-day intervals. After 2 courses of this therapy, metastasis of lung resions had disappeared, leaving the side effect of leukopenia. After two courses of this treatment, we have continued the chemotherapy with a smaller dosage. Unfortunately, at the present time of 20 months after his first visit, metastasis to the abdominal wall was revealed and an aggravation tendency could not be prevented, although, the primary lesion had been kept in good condition without erosion or nodules. Pacritaxel should be recommended as an alternative treatment for angiosarcoma of the scalp. [
Skin Cancer (Japan) 2004; 19: 107-111]
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Mariko KUME
2004 Volume 19 Issue 1 Pages
112-115
Published: March 31, 2004
Released on J-STAGE: August 05, 2010
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We reported a case of squamous cell carcinoma (SCC) arising in an epidermal cyst on the sacrum. The patient was a 55-year-old man who had a history of a mass since 1997. Histpathologically, there was a cystic lesion composed of a benign squamous epithelium with a transition to SCC. After the surgical treatment, the patient was treated with four cycles of intramuscular injection of peplomycine sulfate. The patient is alive without local recurrence or distant metastasis at eight months postoperatively. [
Skin Cancer (Japan) 2004; 19: 112-1151]
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Naoaki FUJITA, Sayaka SUZUKI, Motohito YAMADA, Matsuyosi MAEDA
2004 Volume 19 Issue 1 Pages
116-119
Published: March 31, 2004
Released on J-STAGE: August 05, 2010
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A 54-year-old man had a slowly enlarging tumor of two years' duration on his left cheek.
The tumor was composed of cribriform and tubular masses of basaloid cells. Perineural invasion was observed. The microscopical findings were typical of true adenoid cystic carcinoma (ACC).
Primary ACC of the skin is rare. Only 10 cases have been published in the recent Japanese language literature. [
Skin Cancer (Japan) 2004; 19: 116-119]
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Masato KUROKAWA, Nobuyuki YAMADA, Naoya YUKIOKA, Yuka HAMORI, Kazuo NO ...
2004 Volume 19 Issue 1 Pages
120-123
Published: March 31, 2004
Released on J-STAGE: August 05, 2010
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It is well known that malignant melanoma arises in a large congenital pigmented nevus. We report a case of basal cell carcinoma arising in a large congenital pigmented nevus.
A 45-year-old woman had a congenital pigmented nevus on the left inguinal region that measured 23×17cm. The patient noticed a red nodule on the nevus in September 2000. When she visited our hospital on August 24, 2001, the dome-shaped nodule 4×4×4cm in size was elastic hard. The left inguinal lymph nodes were swollen. We excised the tumor, and the nevus was doubted to have been a malignant melanoma. Wide excision of the lesion including left inguinal lymph nodes was performed. However, the histopathological diagnosis was basal cell carcinoma, and the lymph nodes revealed no metastasis. [
Skin Cancer (Japan) 2004; 19: 120-123]
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Noriyuki SUZUKI, Naoaki FUJITA, Motohito YAMADA, Matsuyoshi MAEDA, Shi ...
2004 Volume 19 Issue 1 Pages
124-127
Published: March 31, 2004
Released on J-STAGE: August 05, 2010
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We report a case of cutaneous Rosai-Dorfman disease (RDD) rising in a 52-year-old Japanese female with two nodules: one was a red nodule on her cheek and the other was a subcutaneous nodule on her chest. Histopathological analysis revealed that the nodules were composed of many histiocytes that were positive to S100, but negative to CD1a showing “emperipolesis”. We diagnosed her with cutaneous RDD based on the histological findings since she had no other lymphadenopathy or extranodal involvement. RDD derived from the skin without lymph node involvement is rare worldwide with approximately 50 cases reported. No cases have been reported in Japan. [Skin Cancer (Japan) 2004; 19: 124-127]
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Hiromasa SASAKI, Miyuki OHASHI, Eiko TOICHI, Takao TACHIBANA, Yoshiki ...
2004 Volume 19 Issue 1 Pages
128-131
Published: March 31, 2004
Released on J-STAGE: August 05, 2010
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A case of clone-negative Sézary syndrome is reported. The patient was a 69-year-old male and showed the classical trias of Sézary syndrome, that is erythrodermia, generalized lymphadenopathy and neoplastic T-cells in skin, lymph nodes and peripheral blood. There is at present no consensus on the diagnostic criteria of Sézary syndrome, if T-cell clonality is not detected in peripheral blood with Southern blotting. The EORTC group demonstrates T-cell clonality is getting major as a diagnostic criterion of Sézary syndrome, which is generally accepted. However, we suppose such cases like ours are present, and should be called clone-negative or nonclonal Sézary syndrome. In addition, we have to carefully observe whether these cases advance to real Sézary syndrome with T-cell clonality, though these cases are not naturally included into cutaneous T-cell lymphomas. [
Skin Cancer (Japan) 2004; 19: 128-131]
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Haruko TARAO, Yoshimi OSHITANI, Yasuhiko TAMADA, Yoshinari MATSUMOTO, ...
2004 Volume 19 Issue 1 Pages
132-135
Published: March 31, 2004
Released on J-STAGE: August 05, 2010
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The patient was a 21-year-old woman. In May 2000, infiltrative erythema began appearing occasionally on her limbs, and after about 6 months a tumor appeared on the erythema of her right calf. This was diagnosed as CD8-positive cutaneous T-cell lymphoma (CD8+CTCL). The tumor disappeared with weekly CHOP therapy (×5), and she entered a state of remission. In November 2002, she was examined with complaints of fever 38°C, swelling of the right tonsil, and neck pain. Tonsil biopsy revealed an image of CD8-positive malignant lymphoma infiltration, and recurrence of the CD8+CTCL seemed likely. CD8-positive tumor cells were also found in the spinal fluid, and findings of intraspinal dissemination were seen on MRI. The swelling of the right tonsil disappeared following various chemo-and radiotherapies, and the tumor cells in the spinal fluid decreased. Her course was favorable, but she suffered complications with DIC and died on March 27. [
Skin Cancer (Japan) 2004; 19: 132-135]
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