Efficacy of bath-psoralen and ultraviolet A therapy for mycosis fungoides - retrospective analysis of 62 cases.

Photochemotherapy with psoralen and ultraviolet A (PUVA) is widely used for refractory skin diseases. Bathwater delivery of 8-methoxypsoralen (8-MOPS) with subsequent UVA irradiation (bath-PUVA) or oral administration of 8-MOPS with UVA is used to treat mycosis fungoides. We retrospectively analyzed 62 patients with mycosis fungoides (8 stage IA, 30 stage IB, 5 stage IIB, 18 stage IIIA, and 1 stage IVA2) treated with bath-PUVA at the Dermatology Clinic of Nagoya City University Hospital from November 2004 to December 2013. A complete response was achieved in 37 (59.7%) patients, a partial response was achieved in 16 (25.8%), and stable disease was achieved in 6 (9.7%). Progressive disease was observed in 3 (4.8%) patients. Almost all patients in stage IA/IB achieved a complete response. Of the 5 stage IIB patients, 2 achieved a partial response, 1 achieved stable disease, and 2 had progressive disease. The serum concentrations of soluble interleukin-2 receptor and lactate dehydrogenase decreased significantly following treatment with bath-PUVA (p < 0.001). We examined the risk factors of patients whose stage progressed despite PUVA treatment. A multivariate Cox regression analysis of risk factors associated with stage progression yielded a hazard ratio of 28.5 for stage IIb. Treatment with bath-PUVA is highly effective in the early stages of mycosis fungoides, and partially effective in advanced stages.

Heat immunotherapy using magnetic nanoparticles and dendritic cells for T-lymphoma.

Dendritic cells (DCs) are potent antigen-presenting cells that play important roles in regulating immune responses in cancer. Immunotherapy using these immunocytes has become an accepted therapeutic modality. We previously reported that hyperthermia using magnetic nanoparticles induces antitumor immunity, which could be activated by adjuvant including cytokines. In the present study, we investigated the therapeutic effects of hyperthermia combined with DC immunotherapy on mouse EL4 T-lymphoma. 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 an EL4 nodule in C57BL/6 mice, which were subjected to AMF for 30 min. The temperature at the surface of the tumor reached 45 degrees C and was maintained by controlling the magnetic field intensity. Hyperthermia treatment was repeated twice with 24 h intervals. After hyperthermia, immature DCs were directly injected into the EL4 nodule. As a result, complete regression of tumors in 75% (6/8) of the mice was observed, while the percentage of complete regression of tumors was 12.5% (1/8) in the case of mice treated by hyperthermia alone. This novel cancer therapy, which we have termed "heat immunotherapy", may be applicable to patients with advanced malignancies.

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.

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.

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.