Combined epigenetic and immunotherapy for blastic and classical mantle cell lymphoma

Classical MCL (cMCL) constitutes 6-8% of all B cell NHL. Despite recent advances, MCL is incurable except with allogeneic stem cell transplant. Blastic mantle cell lymphoma (bMCL) is a rarer subtype of cMCL associated with an aggressive clinical course and poor treatment response, frequent relapse and poor outcomes. We treated 13 bMCL patients with combined epigenetic and immunotherapy treatment consisting of vorinostat, cladribine and rituximab (SCR). We report an increased OS greater than 40 months with several patients maintaining durable remissions without relapse for longer than 5 years. This is remarkably better then current treatment regimens which in bMCL range from 14.5-24 months with conventional chemotherapy regimens. We demonstrate that the G/A870 CCND1 polymorphism is predictive of blastic disease, nuclear localization of cyclinD1 and response to SCR therapy. The major resistance mechanisms to SCR therapy are loss of CD20 expression and evasion of treatment by sanctuary in the CNS. These data indicate that administration of epigenetic agents improves efficacy of anti-CD20 immunotherapies. This approach is promising in the treatment of MCL and potentially other previously treatment refractory cancers. © 2022 LeBlanc et al.Open access articleThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Evidence of Sex-specific Differences in Masticatory Jaw Movement Patterns

The complexity of human oral functional movements has not been studied in detail quantitatively, and only recently have studies begun to evaluate whether such movements contain sex-specific characteristics. Therefore, the purposes of this study were: (1) to quantify in detail the jaw movements and associated masticatory electromyographic activity occurring during gum chewing, and (2) to explore these data for evidence of sex specificity. Fourteen male and 17 female subjects participated in the study. Approximately 11 right- and 11 left-sided chewing cycles and associated masticatory electromyographic activity were sampled from each subject. The samples were quantified into 165 variables per chewing cycle, averaged to create a single multivariate vector for each subject, and then analyzed by a step-wise discriminant analysis. With a combination of 6 variables, a jackknifed cross-validation test found the probability of correct classification to be 93.5%. These findings support the hypothesis that masticatory jaw movements contain sex-specific features.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66870/2/10.1177_00220345970760031301.pd