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.

     

Vertical Bone Augmentation Using Different Osteoconductive Scaffolds Combined with Barrier Domes in the Rat Calvarium

Purpose: To compare the regenerative potential for vertical bone augmentation of various osteoconductive scaffolds when used in conjunction with barrier domes. Materials and Methods: Following exposure and perforation of the calvarium, a gold occlusive dome was filled with the tested scaffold and anchored by fixation screws. Flaps were repositioned and secured. The four treatment groups, three to five rats each, were as follows: Bio‐Oss collagen (BOC), β‐tricalcium phosphate (TCP), collagen sponge (COL), and empty domes (C). Rats were sacrificed 8 weeks later, and specimens were prepared for histological and histomorphometric analysis. Vertical bone height and total tissue height were measured. Results: The newly regenerated bone appeared mature, highly vascularized, and with no signs of inflammation. Vertical bone height in the TCP group (mean 2.04 ± 0.2 mm) was greater than all other groups (0.76 ± 0.02, 1.52 ± 0.18, and 1.77 ± 0.61 mm for the BOC, C, and COL, respectively) but significantly only for the BOC group (p = .0145). Total tissue height was significantly higher (p < .0001) in both BOC and TCP groups (4.48 ± 0.23 and 5.5 ± 0.24 mm, respectively) compared with COL (3.22 ± 0.11 mm) and C (2.39 ± 0.3 mm) groups. Conclusion: TCP in conjunction with barrier dome resulted in greater vertical bone augmentation in the calvarium of rats.     

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 influence of the sacrificial agent nature on transformations of the Zn(OH)2/Cd0.3Zn0.7S photocatalyst during hydrogen production under visible light

Photocatalysts based on zinc hydroxide and a solid solution of CdS and ZnS were prepared via the precipitation method and used for photocatalytic hydrogen production from aqueous solutions of inorganic (Na₂S/Na₂SO₃) and organic (ethanol) sacrificial agents. The photocatalysts were tested in cyclic experiments for hydrogen evolution and studied using X-ray diffraction (XRD), UV-Vis diffuse reflectance spectroscopy, high-resolution transmission electron microscopy (HRTEM), energy-dispersive X-ray spectroscopy (EDX), and X-ray photoelectron spectroscopy (XPS) techniques. Different transformations of the β-Zn(OH)₂ co-catalyst were observed in the presence of inorganic and organic sacrificial agents; namely, ZnS was formed in Na₂S/Na₂SO₃ solution, whereas the formation of ε-Zn(OH)₂ was detected in solution with ethanol. The composite Zn(OH)₂/Cd_1−xZn_xS photocatalysts have great potential in various photocatalysis processes (e.g., hydrogen production, CO₂ reduction, and the oxidation of organic contaminants) under visible light.

The nature of the sacrificial agent affects the transformations of a Zn(OH)₂ co-catalyst during photocatalytic hydrogen production.     

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.     

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...     

Cerebrovascular inflammation promotes the formation of brain metastases

Brain metastases are the most prevalent intracranial malignancy. Patient outcome is poor and treatment options are limited. Hence, new avenues must be explored to identify potential therapeutic targets. Inflammation is a known critical component of cancer progression. Intratumoral inflammation drives progression and leads to the release of circulating tumor cells (CTCs). Inflammation at distant sites promotes adhesion of CTCs to the activated endothelium and then initiates the formation of metastases. These interactions mostly involve cell adhesion molecules expressed by activated endothelial cells. For example, the vascular cell adhesion molecule-1 (VCAM-1) is known to promote transendothelial migration of cancer cells in different organs. However, it is unclear whether a similar mechanism occurs within the specialized environment of the brain. Our objective was therefore to use molecular imaging to assess the potential role of VCAM-1 in promoting the entry of CTCs into the brain. First, magnetic resonance imaging (MRI) and histological analyses revealed that cerebrovascular inflammation induced by intracranial injection of lipopolysaccharide significantly increased the expression of VCAM-1 in the Balb/c mouse brain. Next, intracardiac injection of 4T1 mammary carcinoma cancer cells in animals with cerebrovascular inflammation yielded a higher brain metastasis burden than in the control animals. Finally, blocking VCAM-1 prior to 4T1 cells injection prevented this increased metastatic burden. Here, we demonstrated that by contributing to CTCs adhesion to the activated cerebrovascular endothelium, VCAM-1 improves the capacity of CTCs to form metastatic foci in the brain.