Phase II study of oxaliplatin for treatment of patients with mucosa-associated lymphoid tissue lymphoma.

PURPOSE: Various chemotherapeutic regimens have been applied for treatment of mucosa-associated lymphoid tissue (MALT) lymphoma, but no standard regimen has been identified to date. In view of the activity of oxaliplatin (L-OHP) in various types of lymphoma, we performed a phase II study to evaluate the activity of L-OHP for treatment of MALT lymphoma. The primary objective of this study was to determine the objective response rate according to WHO standard criteria. PATIENTS AND METHODS: A total of 16 patients with MALT lymphoma of various sites of origin (four of the ocular adnexa, five of the salivary glands, three of the stomach, two of the lung, and one of the colon and the breast) were administered L-OHP at a dose of 130 mg/m2 infused during 2 hours every 3 weeks. Restaging was performed every two cycles; treatment was continued until complete remission (CR) or for a maximum of six cycles in responders. RESULTS: Sixty-five cycles were administered (median, four; range, two to six); toxicity consisted of transient sensory neuropathy in eight patients and nausea/emesis WHO grade 2 in two patients, whereas hematologic adverse effects (thrombocytopenia and leukocytopenia grade 2) occurred in only one patient each. Fifteen patients responded to chemotherapy, with nine achieving CR (56%), six (37.5%) achieving partial response, and one achieving stable disease; the median time to response was 4 months (range; 2 to 4 months). CONCLUSION: These data suggest L-OHP is a highly active agent for treatment of MALT lymphoma. However, a longer follow-up is needed to judge whether these remissions are durable.     

IL-24 intrinsically regulates Th17 cell pathogenicity in mice

In certain instances, Th17 responses are associated with severe immunopathology. T cell–intrinsic mechanisms that restrict pathogenic effector functions have been described for type 1 and 2 responses but are less well studied for Th17 cells. Here, we report a cell-intrinsic feedback mechanism that controls the pathogenicity of Th17 cells. Th17 cells produce IL-24, which prompts them to secrete IL-10. The IL-10–inducing function of IL-24 is independent of the cell surface receptor of IL-24 on Th17 cells. Rather, IL-24 is recruited to the inner mitochondrial membrane, where it interacts with the NADH dehydrogenase (ubiquinone) 1 α subcomplex subunit 13 (also known as Grim19), a constituent of complex I of the respiratory chain. Together, Grim19 and IL-24 promote the accumulation of STAT3 in the mitochondrial compartment. We propose that IL-24–guided mitochondrial STAT3 constitutes a rheostat to blunt extensive STAT3 deflections in the nucleus, which might then contribute to a robust IL-10 response in Th17 cells and a restriction of immunopathology in experimental autoimmune encephalomyelitis.     

The dopamine D2 receptor gene, perceived parental support, and adolescent loneliness: longitudinal evidence for gene-environment interactions

Background: Loneliness is a common problem in adolescence. Earlier research focused on genes within the serotonin and oxytocin systems, but no studies have examined the role of dopamine‐related genes in loneliness. In the present study, we focused on the dopamine D2 receptor gene (DRD2). Methods: Associations among the DRD2, sex, parental support, and loneliness were examined in a longitudinal study spanning five annual waves (N = 307). Results: Using Latent Growth Curve Modeling, DRD2 genotype was not directly related to loneliness. Interactions were found between parental support and DRD2 genotype, showing that adolescents with the A2A2 genotype who perceived little support from their parents had the highest baseline levels of loneliness. Adolescents with an A1 allele were not susceptible to the rewarding effect of parental support. Conclusions: The present study is the first to examine the role of the DRD2 genotype in loneliness. Our results contribute to a further understanding of the environmental and genetic basis of loneliness in adolescence.     

Deoxyribonucleic acid-damaged sperm in cryopreserved-thawed specimens from cancer patients and healthy men

A similarity was found between the percentage of thawed, DNA-damaged spermatozoa in cancer patients and that in candidates to become sperm bank donors who had low sperm cryofreezability. Both groups were significantly different from the sperm bank donor group. It is suggested that the higher rate of DNA fragmentation in sperm from cancer patients compared with sperm bank donors is apparently a result of selecting donors by the level of sperm cryofreezability (i.e., high), rather than a direct effect of an existing malignancy.