Skin directed treatment of cutaneous T-cell lymphomas, case report

Cutaneous T-cell lymphomas are rare diseases with significant differences in their clinical course and prognosis. The choice of treatment basically depends on the stage, in the early stages of the disease only skin directed treatment is recommended. With most of the treatment modalities, complete cure is not possible, only long-term remission can be achieved. The authors report the case of a 52-year-old female patient who developed extensive annular, erythematous, infiltrated plaques in the spring of 2019. Histological examination confirmed mycosis fungoides, imaging did not show lymph node or other organ involvement. Given the disease (stage IB), PUVA treatment was initiated. After a total of 21 sessions of phototherapy from September 2019, the patient underwent complete remission. The authors provide a detailed review of skin directed treatment options for mycosis fungoides based on current international recommendations.

Slowly Repaired Bulky DNA Damages Modulate Cellular Redox Environment Leading to Premature Senescence

Treatments on neoplastic diseases and cancer using genotoxic drugs often cause long-term health problems related to premature aging. The underlying mechanism is poorly understood. Based on the study of a long-lasting senescence-like growth arrest (10-12 weeks) of human dermal fibroblasts induced by psoralen plus UVA (PUVA) treatment, we here revealed that slowly repaired bulky DNA damages can serve as a “molecular scar” leading to reduced cell proliferation through persistent endogenous production of reactive oxygen species (ROS) that caused accelerated telomere erosion. The elevated levels of ROS were the results of mitochondrial dysfunction and the activation of NADPH oxidase (NOX). A combined inhibition of DNA-PK and PARP1 could suppress the level of ROS. Together with a reduced expression level of BRCA1 as well as the upregulation of PP2A and 53BP1, these data suggest that the NHEJ repair of DNA double-strand breaks may be the initial trigger of metabolic changes leading to ROS production. Further study showed that stimulation of the pentose phosphate pathway played an important role for NOX activation, and ROS could be efficiently suppressed by modulating the NADP/NADPH ratio. Interestingly, feeding cells with ribose-5-phosphate, a precursor for nucleotide biosynthesis that produced through the PPP, could evidently suppress the ROS level and prevent the cell enlargement related to mitochondrial biogenesis. Taken together, these results revealed an important signaling pathway between DNA damage repair and the cell metabolism, which contributed to the premature aging effects of PUVA, and may be generally applicable for a large category of chemotherapeutic reagents including many cancer drugs.