Activity of Aloe arborescens leaf extracts: in vitro effects on Human Adenocarcinoma HT-29 cell line and free-radical species.

Aloe arborescens Mill. (syn. Candelabra Aloe; Xanthorrhoeaceae) is native to South Africa; in Italy it is grown for ornamental, therapeutic and cosmetic uses. Various Aloe spp. have been used since ancient times and have a well-documented history of use as medicines. Nowadays, it is widely studied as potential anticancer, antidiabetic, antimicrobial and for several other uses. The presence of aloin, aloe-emodin, polysaccharides, mannose and acemannan was reported in whole-leaf preparations. The aim of the present research was to study Aloe arborescens leaf extracts, also to improve the uses of Aloe since many products are marketed also in Western countries. For this purpose, methanolic and ethanolic extracts were obtained from freeze-dried leaves, and then studied using: a) HPLC-DAD analysis to determine aloins and aloe-emodin contents, b) two radical-scavenging assays to assess the radical scavenger activity, and 3) MTT assay on colorectal adenocarcinoma cell line (HT29 cells) to evaluate cell viability

Inter- vs. Intra-Speaker Variation in Mixed Heritage Syntax: A Statistical Analysis

Based on the novel data pertaining to five syntactic phenomena (the position of the finite verb in embedded clauses, in sentences with a modal verb, negative concord, the position of focused light/heavy objects in main clauses with a complex tense and scrambling) in the heritage language Mòcheno collected via original fieldwork, we show that there are two populations – one exhibiting intra-speaker variation between German and Italian word orders, and one lacking it; and these two populations are the result of diatopic variation and, to a lesser extent, of diastratic variation. The results achieved using quantitative statistical analysis are partially convergent with those arrived at via the traditional theoretical syntax for Mòcheno, but our analysis has allowed us to shed new light on a series of phenomena that have been neglected or poorly understood thus far. More specifically, and for the first time, we discovered that there is a micro-variation resulting from diastratic (age) variation within the Roveda variety, which represents the only case in Mòcheno in which age is a relevant factor in determining variation. We also show that the traditional claim that the Palù variety is ‘more German’ than is the other Mòcheno variety is to be confirmed; however, we could refine it by showing that German word orders are also accepted by speakers of other varieties and that the acceptability of these word orders in competition with the Italian syntax is not due to their age (no diastratic variation). Finally, we show that the acceptance of German word orders across speakers varies according to the phenomenon investigated: German word orders are more likely to be accepted in sentences featuring a negation, whereas German word orders are more likely to be rejected in embedded clauses. Based on this fine-grained description of the distribution of OV/VO word orders across different contexts and groups and the available theoretical account for the derivation of OV word order given by Cognola (2013 b), we propose that the observed variation can be parametrised along the lines of recent developments of Parameter Theory (Roberts 2012; Biberauer, Holmberg, Roberts & Sheehan 2014 a.o.). More specifically, we propose that the movement of the non-finite verb form to lowForce°, which is responsible for OV in Mòcheno, can be captured in terms of a parametric hierarchy. When verb movement takes place in all syntactic conditions, including with all non-finite verb forms and when the auxiliary has not moved out of v° to Spec,CP, a macroparametric effect obtains which corresponds to the system instantiated by the Palù variety. The mesoparameter corresponds to a system in which the movement to the non-finite verb form can only be found when v° is empty, i.e. in main declarative clauses. The fact that for a subgroup of speakers from Fierozzo and Roveda OV word order is accepted with modal verbs follows from a microparamter: the movement of the non-finite verb form to lowFocus° can only take place with non-finite verbs. Finally, the fact that OV is obligatory for nearly all groups is captured in terms of a nanoparamenter associated with negative constituents

131I Whole-Body Scan Incidental Uptake Due to Spermatocele

A 46-year-old man with papillary thyroid cancer post total thyroidectomy was referred for post radioiodine (I) whole-body scan. Whole-body images revealed intense I uptake in the bed thyroid and a focal abnormal uptake in the testicular area. Subsequent SPECT/CT demonstrated that the focal uptake corresponded to the left epididymis, and the pathology report revealed a spermatocele with no immunohistochemical features for thyroid tissue. Many cases of unexpected radioiodine uptake have been reported, and spermatocele could be counted for another possibility of incidental I uptake despite an unclear mechanism

Personalized therapeutic strategies in HER2-driven gastric cancer.

Trastuzumab is the only approved targeted therapy in patients with HER2-amplified metastatic gastric cancer (GC). Regrettably, in clinical practice, only a fraction of them achieves long-term benefit from trastuzumab-based upfront strategy. To advance precision oncology, we investigated the therapeutic efficacy of different HER2-targeted strategies, in HER2 "hyper"-amplified (≥ 8 copies) tumors. We undertook a prospective evaluation of HER2 targeting with monoclonal antibodies, tyrosine kinase inhibitors and antibody-drug conjugates, in a selected subgroup of HER2 "hyper"-amplified gastric patient-derived xenografts (PDXs), through the design of ad hoc preclinical trials. Despite the high level of HER2 amplification, trastuzumab elicited a partial response only in 2 out of 8 PDX models. The dual-HER2 blockade with trastuzumab plus either pertuzumab or lapatinib led to complete and durable responses in 5 (62.5%) out of 8 models, including one tumor bearing a concomitant HER2 mutation. In a resistant PDX harboring KRAS amplification, the novel antibody-drug conjugate trastuzumab deruxtecan (but not trastuzumab emtansine) overcame KRAS-mediated resistance. We also identified a HGF-mediated non-cell-autonomous mechanism of secondary resistance to anti-HER2 drugs, responsive to MET co-targeting. These preclinical randomized trials clearly indicate that in HER2-driven gastric tumors, a boosted HER2 therapeutic blockade is required for optimal efficacy, leading to complete and durable responses in most of the cases. Our results suggest that a selected subpopulation of HER2-"hyper"-amplified GC patients could strongly benefit from this strategy. Despite the negative results of clinical trials, the dual blockade should be reconsidered for patients with clearly HER2-addicted cancers