Evaluation of the MD Anderson tumor score for diffuse large B-cell lymphoma in the rituximab era.

OBJECTIVES: Diffuse large B-cell lymphoma (DLBCL) is an aggressive heterogeneous lymphoma with standard treatment. However, 30%-40% of patients still fail, so we should know which patients are candidates for alternative therapies. IPI is the main prognostic score but, in the rituximab era, it cannot identify a very high-risk (HR) subset. The MD Anderson Cancer Center reported a score in the prerituximab era exclusively considering tumor-related variables: Tumor Score (TS). We aim to validate TS in the rituximab era and to analyze its current potential role. METHODS: From GELTAMO DLBCL registry, we selected those patients homogeneously treated with R-CHOP (n = 1327). RESULTS: Five-years PFS and OS were 62% and 74%. All variables retained an independent prognostic role in the revised TS (R-TS), identifying four different risk groups, with 5-years PFS of 86%, 71%, 50%, and very HR (28%). With a further categorization of three variables of the original TS (Ann Arbor Stage, LDH and B2M), we generated a new index that allowed an improvement in HR assessment. CONCLUSIONS: (a) All variables of the original TS retain an independent prognostic role, and R-TS remains predictive in the rituximab era; (b) R-TS and additional categorization of LDH, B2M, and AA stage (enhanced TS) increased the ability to identify HR subsets.

Thermogenic capacity in subterranean Ctenomys: Species-specific role of thermogenic mechanisms.

One way to understand ecological patterns of species is to determine their physiological diversity on a large geographic and/or temporal scales, in a context of hierarchical biodiversity framework. In particular, macrophysiological studies analyze how environmental factors affect the physiology and therefore the distribution of species. Subterranean species are an excellent model for evaluating the large-scale effects of ambient temperature (Ta) conditions on thermal physiology and distribution, due to their extensive use of burrows that provide a relatively thermal stable environment. Species belonging to the genus Ctenomys are all subterranean and endemic of South America. Cold induced maximum metabolic rate (MMR), basal metabolic rate (BMR) and non shivering thermogenesis (NST) were analyzed, as well as the expression of uncoupled proteins (UCP) in brown adipose tissue (BAT). Biogeographical variables appear to have no effect MMR experimentally induced by cold condition within Ctenomys. Also, mechanisms of heat production are species-specific, varying from a combination of ST and NST to a complete use of shivering mechanisms. This pattern is correlated at tissue level, since species that use only ST show a smaller interscapular BAT patch, not detectable presence of UCP1 and low COX activity. Thus, other factors, including body mass, that constrain cold induced MMR could affect thermogenic variability among Ctenomys. In the evolutionary timescale, if low O2 levels of burrows impose a ceiling in cold induced MMR, and ST is enhanced due to species-specific life history traits, such as digging effort, then the observed differences among Ctenomys species might be explained.

Modulation of white adipose tissue proteome by aging and calorie restriction.

Aging is associated with an accrual of body fat, progressive development of insulin resistance and other obesity comorbidities that contribute to decrease life span. Caloric restriction (CR), which primarily affects energy stores in adipose tissue, is known to extend life span and retard the aging process in animal models. In this study, a proteomic approach combining 2-DE and MS was used to identify proteins modulated by aging and CR in rat white adipose tissue proteome. Proteomic analysis revealed 133 differentially expressed spots, 57 of which were unambiguously identified by MS. Although CR opposed part of the age-associated protein expression patterns, many effects of CR were on proteins unaltered by age, suggesting that the effects of CR on adipose tissue are only weakly related to those of aging. Particularly, CR and aging altered glucose, intermediate and lipid metabolism, with CR enhancing the expression of enzymes involved in oxalacetate and NADPH production, lipid biosynthesis and lipolysis. Consistently, insulin-ß and ß3-adrenergic receptors were also increased by CR, which denotes improved sensitivity to lipogenic/lipolytic stimuli. Other beneficial outcomes of CR were an improvement in oxidative stress, preventing the age-associated decrease in several antioxidant enzymes. Proteins involved in cytoskeleton, iron storage, energy metabolism and several proteins with novel or unknown functions in adipose tissue were also modulated by age and/or CR. Such orchestrated changes in expression of multiple proteins provide insights into the mechanism underlying CR effects, ultimately allowing the discovery of new markers of aging and targets for the development of CR-mimetics.