Mogamulizumab-induced photosensitivity in patients with mycosis fungoides and other T-cell neoplasms.

BACKGROUND: Mogamulizumab (Mog) is a defucosylated, therapeutic monoclonal antibody, targeting CCR4 and was first approved in Japan for the treatment of adult T-cell leukaemia/lymphoma (ATLL), followed by cutaneous T-cell lymphoma and peripheral T-cell lymphoma. OBJECTIVE: To retrospectively investigate development of photosensitivity in patients with mycosis fungoides and other T-cell neoplasms after treatment with Mog. METHODS: We treated seven cutaneous lymphoma patients with Mog. Upon combination treatment with narrow-band UVB, we noticed that four patients developed photosensitivity dermatitis following Mog therapy, including two cases of mycosis fungoides, one case of adult T-cell leukaemia/lymphoma and one case of EB virus-associated T-cell lymphoproliferative disorder. Phototest was performed with UVA and UVB, and immunohistochemical staining for CD4, CD8 and Foxp3 was conducted in both photosensitivity and lymphoma lesions. RESULTS: Phototest revealed that the action spectrum of the photosensitivity was UVB in three cases and both UVB and UVA in one case. Histopathologically, the photosensitive lesions were characterized by a lichenoid tissue reaction with a CD8+ T cell-dominant infiltrate, sharing the feature with chronic actinic dermatitis, an autoreactive photodermatosis with a cytotoxic T-cell response. Foxp3+ regulatory T cells (Tregs) were decreased in the photosensitivity lesions compared with the lymphoma lesions. CONCLUSION: Increased incidence of photosensitivity reaction was observed during Mog treatment. Decreased number of Tregs in the lesional skin suggests that this reaction is possibly induced by autoreactive cytotoxic T cells.

Thioredoxin: a redox-regulating cellular cofactor for glucocorticoid hormone action. Cross talk between endocrine control of stress response and cellular antioxidant defense system.

Adaptation to stress evokes a variety of biological responses, including activation of the hypothalamic-pituitary-adrenal (HPA) axis and synthesis of a panel of stress-response proteins at cellular levels: for example, expression of thioredoxin (TRX) is significantly induced under oxidative conditions. Glucocorticoids, as a peripheral effector of the HPA axis, exert their actions via interaction with a ligand-inducible transcription factor glucocorticoid receptor (GR). However, how these stress responses coordinately regulate cellular metabolism is still unknown. In this study, we demonstrated that either antisense TRX expression or cellular treatment with H2O2 negatively modulates GR function and decreases glucocorticoid-inducible gene expression. Impaired cellular response to glucocorticoids is rescued by overexpression of TRX, most possibly through the functional replenishment of the GR. Moreover, not only the ligand binding domain but the DNA binding domain of the GR is also suggested to be a direct target of TRX. Together, we here present evidence showing that cellular glucocorticoid responsiveness is coordinately modulated by redox state and TRX level and propose that cross talk between neuroendocrine control of stress responses and cellular antioxidant systems may be essential for mammalian adaptation processes.

Outbreak of Nocardia farcinica infection with the same pattern in randomly amplified polymorphic DNA analysis.

We experienced three cases of nocardiosis by Nocardia farcinica in the same ward within a six-month period. The result of gene analysis by randomly amplified polymorphic DNA gave the same pattern. Thus, these three cases were considered to be caused by the same strain of N. farcinica, implying the presence of nosocomial infection.

Alteration of biologic behavior of a rat leukemia by different routes of passage.

Two clonal leukemia cell lines exhibiting diploidy or tetraploidy were isolated separately from a mother cell population of rat myelogenous leukemia DBLA-6 (induced by 1-butyl-1-nitrosourea), and their biologic characteristics altered during serial iv or ip passages in Donryu rats were examined. In early generations after the establishment of the clones, leukemia-inducing capacities were clearly demonstrated only in the diploid clone and were characterized as follows: a) release of leukemia cells into the peripheral blood after inoculation, and b) infiltration, and growth of leukemia cells in the bone marrow and spleen. After repeated iv passages, however, leukemia-inducing capacity was greater not only in the diploid but also in the tetraploid clone. By serial ip passages, this capacity was never acquired but was gradually lost even in the diploid clone. Cell electrophoretic mobility, cell size, or susceptibility to chemotherapeutic agents were also modified. There was a strong correlation between the routes of passage and the direction of the changes: The iv route enhanced or the ip route suppressed the leukemia-inducing capacity. Chromosome constitutions were also changed.

N4-Behenoyl-1-beta-D-arabinofuranosylcytosine as a potential new antitumor agent.

N4-Acyl-1-beta-D-arabinofuranosylcytosines, which are lipophilic antitumor analogs of 1-beta-D-arabinofuranosylcytosine, were dissolved by the use of a detergent, HCO-60, and the differences in the antitumor activities when the drugs were administered in the forms of solution or suspension were compared. N4-Stearoyl-1-beta-D-arabinofuranosylcytosine (NSC 201290), which was the most active compound when administered as an aqueous suspension, diminished in its activities after it had been dissolved into a clear solution, whereas N4-behenoyl-1-beta-D-arabinofuranosylcytosine (NSC 239336) exhibited activities superior to those of the parent compound 1-beta-D-arabinofuranosylcytosine when administered as a solution. Moreover, the high efficacy of this compound was long lasting in the host animal, regardless of the treatment schedules or the presence of the 1-beta-D-arabinofuranosylcytosine-inactivating enzyme, cytidine deaminase.

Antitumor activities of newly synthesized N4-acyl-1-beta-D-arabinofuranosylcytosine.

New derivatives of 1-beta-D-arabinofuranosylcytosine were synthesized and their antitumor activities were tested against mouse leukemia L1210. Among the 50 compounds investigated, a series of N4-acyl derivatives with long-chain saturated fatty acids were found to be highly active. The most active derivatives were N4-stearoly-1-beta-D-arabinofuranosylcytosine, which was administered in the form of suspension, and N4-behenoyl-1-beta-D-arabinofuranosylcytosine given in the form of solution. They were superior to the parent compound, 1-beta-D-arabinofuranosylcytosine, in that smaller dosages exhibited strong activities regardless of the treatment schedule, and they were also resistant to cytidine deaminase.

Purification and characterization of isocitrate dehydrogenase from a hyperthermophilic archaebacterium, Caldococcus noboribetus.

Isocitrate dehydrogenase from a hyperthermophilic archaebacterium Caldococcus noboribetus produced in Escherichia coli was purified. The purification was performed by heat treatment at 80 degrees C followed by single column chromatography. N-terminal amino acid sequencing analysis revealed that the N-terminal methionine is removed from the purified enzyme. Gel filtration analysis suggests that the enzyme has a homodimeric structure with a molecular weight of 90,000. The isoelectric point of the enzyme was estimated to be 5.6 by isoelectric focusing electrophoresis. The circular dichroism spectrum suggests that the enzyme has a secondary structure consisting of 23% alpha-helix and 34% beta-sheet. Enzymatic activity was observed under neutral pH, and the highest specific activity was obtained using cacodylic acid-KOH (pH 7.0) buffer. MgCl2 or MnCl2 was essential for the activity, and KCl concentrations higher than 0.33 M had an inhibitory effect on it. Apparent Km values were 72 and 43 microM for D,L-isocitrate and NADP, respectively. The enzyme showed extremely high stability against heat treatment, and no activity loss was observed by the treatment at 80 degrees C. The specific activity of the enzyme increased as temperature rose. Nearly no activity was observed at 40 degrees C or lower.