Topoisomerase II-alfa gene as a predictive marker of response to anthracyclines in breast cancer

Amplification or deletion of the topoisomerase IIα (TOP2A) gene in breast cancer has been related with responsiveness to anthracyclines-based chemotherapy. The purpose of this study was to evaluate the predictive value of TOP2A gene for the efficacy of neo-adjuvant anthracycline in a population with locally advanced breast cancer. Sixty-two patients were included, and the status of TOP2A gene was determined by in situ hybridization method. Treatment efficacy was determined by clinical and pathological response and overall survival. TOP2A gene alterations were found in 22.6% (21.0% of cases with amplification and 1.6% with deletion), and these tumors were biologically more aggressive, with higher nuclear grade, more frequently with HER2 amplification and inflammatory type. Also in these tumors response to chemotherapy appeared to be increased. There was a higher clinical and pathological response rate (complete pathological response of 21.4% vs. 8.3%), a trend toward longer progression-free survival (82.51 vs. 63.12 months) and a trend to increased overall survival (92.08 months; 95% CI 82.81–101.35 vs. 73.40 months; 95% CI 63.44–83.36; p = 0.113). These results corroborate that the TOP2A gene alterations may play an important role in determining anthracycline sensitivity in breast cancer.     

Estrogen receptor alpha and androgen receptor are commonly expressed in well-differentiated liposarcoma

Background

Liposarcoma (LS) is the second-most common type of soft-tissue sarcoma. Despite advances in knowledge and treatment of this disease, there remains a need for more effective LS therapy. Steroid hormone receptors regulate metabolism in adipocytes. Estrogen receptor alpha (ER), progesterone receptor (PR), and androgen receptor (AR) have been implicated in the pathophysiology of other cancer types. We sought to comprehensively determine temporal expression patterns of these receptors in LS.

Methods

We analyzed 561 histologically subtyped LS specimens from 354 patients for expression of ER, PR, and AR by immunohistochemistry (IHC) using diagnostic-grade reagents and protocols. The fractions of positively stained tumor cells were scored within each specimen. IHC scores were compared across LS subtypes using the Kruskal-Wallis test, and subtypes were compared using Dunn’s post-hoc test. Ages of patients with receptor-positive vs. -negative LS were compared by t-test. Genders and races were compared for hormone receptor positivity using Fisher’s exact test and Chi-square analysis, respectively. Recurrence-free survival was compared between receptor-positive and negative patients by log-rank test. p<?0.05 was considered significant.

Results

ER and AR were frequently expressed in LS, while few tumors expressed PR. Most of the ER?+?and AR?+?samples were of the well-differentiated LS subtype. A smaller fraction of de-differentiated LS expressed ER or AR, but expression was common within well-differentiated regions of tumors histologically classified as de-differentiated LS. In LS specimens from patients who underwent multiple surgeries over time, receptor expression frequently changed over time, which may be attributable in part to intratumor heterogeneity, varying degrees of de-differentiation, and biopsy bias. ER and AR were frequently co-expressed. Receptor status was not significantly associated with gender or race, but AR and PR expression were associated with earlier age at diagnosis. Receptor expression was not associated with altered recurrence-free survival.

Conclusions

ER and AR are commonly expressed in LS, particularly in well-differentiated tumors. These data warrant further functional study to determine receptor function in LS, and the potential efficacy of anti-hormone therapies for the treatment of patients with LS.

     

Fatigue resistance of rotary instruments manufactured using different nickel–titanium alloys: a comparative study

The aim of this study was to investigate whether cyclic fatigue resistance is increased for Controlled Memory (CM) Nickel–Titanium (NiTi) instruments, compared to instruments produced using traditional NiTi and instruments produced using M-Wire alloy. Two groups of NiTi endodontic instruments consisting of identical instrument sizes (constant 0.06 taper and 0.25 tip diameter and constant 0.04 taper and 0.40 tip diameter) were tested: group A compared Hyflex? CM, Vortex ? and ProFile ? size 25 and 0.06 taper and group B compared Hyflex? CM, Vortex? and ProFile? size 40 and 0.04 taper. 10 files from each different subgroup were tested for cyclic fatigue resistance. Mean and standard deviations of the Number of Cycles to Failure (NCF) were calculated for each group and data were statistically analysed (p < 0.05). Hyflex? CM instruments, size 25 and 0.06 taper, and size 40 and 0.04 taper, showed a significant increase in the mean number of cycles to failure when compared with size 25 and 0.06 taper Vortex? and ProFile?. No statistically significant difference (p > 0.05) was noted between Vortex? and ProFile? in the tested sizes. The new manufacturing process involving memory shape heat treatment produced new NiTi rotary files (Hyflex? CM) significantly more resistant to fatigue than instruments produced with other proprietary methods of treatment (Vortex?) and with the traditional NiTi grinding process (ProFile?).     

The specificity of sociotropy-autonomy personality dimensions to depression vs. Anxiety

Previous cognitive vulnerability studies have identified sociotropy/dependency as a personality characteristic related to depression. We evaluated sociotropy in differential prediction of depression vs. anxiety. Participants (70 females, 42 males) were tested on the Beck Depression Inventory (BDI) and the Beck Anxiety Inventory (BAI) at two points in time (T1 and T2), separated by an interval of 4 weeks. The Sociotropy-Autonomy Scale (SAS) was administered at T1. Sociotropy was related moderately to the BDI at T1 and T2, but also to the BAI. Autonomy was related to neither. Hierarchical multiple regression analyses found sociotropy to predict anxiety at T2, but not depression. The issue of cognitive vulnerability marker specificity is discussed.     

Hybrid thermosensitive-mucoadhesive in situ forming gels for enhanced corneal wound healing effect of L-carnosine

PurposeThermosensitive in situ gels have been around for decades but only a few have been translated into ophthalmic pharmaceuticals. The aim of this study was to combine the thermo-gelling polymer poloxamer 407 and mucoadhesive polymers chitosan (CS) and methyl cellulose (MC) for developing effective and long-acting ophthalmic delivery systems for L-carnosine (a natural dipeptide drug) for corneal wound healing.MethodsThe effect of different polymer combinations on parameters like gelation time and temperature, rheological properties, texture, spreading coefficients, mucoadhesion, conjunctival irritation potential, in vitro release, and ex vivo permeation were studied. Healing of corneal epithelium ulcers was investigated in a rabbit’s eye model.ResultsBoth gelation time and temperature were significantly dependent on the concentrations of poloxamer 407 and additive polymers (chitosan and methyl cellulose), where it ranged from <10 s to several minutes. Mechanical properties investigated through texture analysis (hardness, adhesiveness, and cohesiveness) were dependent on composition. Promising spreading-ability, mucoadhesion, transcorneal permeation of L-carnosine, high ocular tolerability, and enhanced corneal epithelium wound healing were recorded for poloxamer 407/chitosan systems.ConclusionIn situ gelling systems comprising combinations of poloxamer-chitosan exhibited superior gelation time and temperature, mucoadhesion, and rheological characteristics suitable for effective long-acting drug delivery systems for corneal wounds.     

Clinical implications of hepatic progenitor cell activation in non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is one of the most prominent causes of liver-related morbidity in the Western world. NAFLD is a chronic disease charac...     

Brain tumor revealed by atrial sinus block

Bradycardia is rare in children and may be asymptomatic or cause fatigue or discomfort leading to syncope. It may be a warning sign of underlying pathology. A check-up for a cardiac or extra-cardiac organic cause should be performed. We report the case of an 8-year-old child admitted to the emergency room for bradycardia with a sino-atrial block that caused syncope. The assessment has objectified a brain tumor. We will discuss the different mechanisms that can explain the occurrence of bradycardia during a brain tumor, and the specificities of the management.     

Patterns of relapse after successful completion of initial therapy in primary central nervous system lymphoma: a case series

Journal of Neuro-Oncology - Primary central nervous system lymphoma (PCNSL) is a subtype of non-Hodgkin’s lymphoma that involves the brain, spinal cord, or leptomeninges, without evidence of...     

Core–Shell Particle Reinforcements—A New Trend in the Design and Development of Metal Matrix Composites

Metal matrix composites (MMCs) are a constantly developing class of materials. Simultaneously achieving a high strength and a high ductility is a challenging task in the design of MMCs. This article aims to highlight a recent trend: the development of MMCs reinforced with particles of core–shell structure. The core–shell particles can be synthesized in situ upon a partial transformation of metal (alloy) particles introduced into a metal matrix. MMCs containing core–shell particles with cores of different compositions (metallic, intermetallic, glassy alloy, high-entropy alloy, metal-ceramic) are currently studied. For metal core–intermetallic shell particle-reinforced composites, the property gain by the core–shell approach is strengthening achieved without a loss in ductility. The propagation of cracks formed in the brittle intermetallic shell is hindered by both the metal matrix and the metal core, which constitutes a key advantage of the metal core–intermetallic shell particles over monolithic particles of intermetallic compounds for reinforcing purposes. The challenges of making a direct comparison between the core–shell particle-reinforced MMCs and MMCs of other microstructures and future research directions are discussed.