Pre-treatment of mice with tumor-conditioned media accelerates metastasis to lymph nodes and lungs: a new spontaneous breast cancer metastasis model

Current spontaneous metastasis models require a long period of observation after establishment of primary tumors to see significant metastatic progression. The degree of metastasis is not consistent among animals: this is problematic since it requires the use of a large number of animals to obtain reliable statistics. Here we report that pre-treatment of animals with tumor-conditioned media (TCM) consistently accelerates spontaneous metastasis in breast cancer. An inguinal breast tumor model facilitated by TCM showed robust anterior metastasis to the axillary and brachial lymph nodes (LN), and the lungs compared to the serum-free media treated group. The LN in TCM-treated animals showed enhanced angiogenesis and lymphangiogenesis. Primary tumors and lungs in TCM-treated animals showed enhanced lymphangiogenesis with no significant change in angiogenesis. TCM-treated animals also showed metastatic dissemination to abdomen from the primary injection site: this would generally enhance metastasis to other organs. In sum, the addition of TCM pre-treatment to current metastasis models results in accelerated and robust metastasis which would enable more efficient evaluation of anti-metastatic agents.     

Development of Laser Welding and Surface Treatment of Metals

This Special Issue on Development of Laser Welding and Surface Treatment of Metals contains as many as twenty-two research articles mainly related to the application of lasers, but also on other welding processes that may be competitive to laser technologies under specific conditions. Despite the introduction of lasers for material processing in the 1960s, the continuous development of laser devices also leads to the development and expansion of laser technology applications. This Special Issue is a compendium of knowledge in the field of fusion welding, the manufacturing of surface layers and coatings with increased wear resistance and tribological characteristics, as well as corrosion resistance and the characterization of coatings and surface layers. The topics of the presented research articles include aspects related to laser welding (eight articles), especially technological conditions, the properties of different types of joints, and analytical and numerical aspects of modelling the laser heat sources. The second dominant issue concerns laser cladding and laser surface treatment of different ferrous and nonferrous metallic and composite materials (six articles). In addition, there are interesting results of the study of fusion welding under forced cooling of the deposit or underwater conditions (four articles), results on the characterization of wear resistance coating produced by different technologies that can be competitive for laser cladding (three articles), and an original study on local strengthening of the thin-walled structure by laser treatment (one article). This Special Issue provides very wide and valuable knowledge based on theoretical and empirical study in the field of laser and fusion welding, laser and related coating technologies, characterization of coatings, and wear phenomena.     

The Influence of Low-Molecular-Weight Monomers (TEGDMA,HDDMA, HEMA) on the Properties of Selected Matrices and Composites Based on Bis-GMA and UDMA

Bisphenol A-glycidyl methacrylate (bis-GMA) and urethane dimethacrylate (UDMA) are usually combined with low-viscosity monomers to obtain more desirable viscosity, handling characteristics and general properties. The present study determined the flexural strength (FS), flexural modulus (FM), diametral tensile strength (DTS), and hardness (HV) of five matrices and composites based on these resins. The polymerization shrinkage stress (PSS) was also studied for the composites. The polymer matrices were formed using bis-GMA and UDMA. TEGDMA, HEMA and HDDMA acted as co-monomers. The composites had 45 wt.% of filler content. The highest FS and FM were obtained from the UDMA/bis-GMA/TEGDMA/HEMA matrix and the composite (matrix + filler). The best DTS values were obtained from the UDMA/bis-GMA/HEMA matrix and the composite. One of the lowest values of FS, FM, and DTS was obtained from the UDMA/bis-GMA/HDDMA matrix and the composite. All the composites demonstrated similar hardness values. The lowest polymerization shrinkage stress was observed for the UDMA/bis-GMA/TEGDMA/HEMA composite, and the highest PSS was observed for the UDMA/bis-GMA/TEGDMA/HDDMA composite. The addition of HEMA had a positive effect on the properties of the tested materials, which may be related to the improved mobility of the bis-GMA and UDMA monomers.     

A comparison of replicative senescence and doxorubicin-induced premature senescence of vascular smooth muscle cells isolated from human aorta

Senescence of vascular smooth muscle cells (VSMCs) contributes to aging as well as age-related diseases of the cardiovascular system. Senescent VSMCs have been shown to be present in atherosclerotic plaques. Both replicative (RS) and stress-induced premature senescence (SIPS) accompany cardiovascular diseases. We aimed to establish the signature of RS and SIPS of VSMCs, induced by a common anticancer drug, doxorubicin, and to discover the so far undisclosed features of senescent cells that are potentially harmful to the organism. Most of the senescence hallmarks were common for both RS and SIPS; however, some differences were observed. 32 % of doxorubicin-treated cells were arrested in the G2/M phase of the cell cycle, while 73 % of replicatively senescing cells were arrested in the G1 phase. Moreover, on the basis of alkaline phosphatase activity measurements, we show that a 7-day treatment with doxorubicin (dox), does not cause precocious cell calcification, which is a characteristic feature of RS. We did not observe calcification even though after 7 days of dox-treatment many other markers characteristic for senescent cells were present. It can suggest that dox-induced SIPS does not accelerate the mineralization of vessels. We consider that detailed characterization of the two types of cellular senescence can be useful in in vitro studies of potential anti-aging factors.     

Risk of lymph node metastases in multifocal papillary thyroid cancer associated with Hashimoto's thyroiditis

Aims

The aim of this study was to evaluate the risk factors of lymph nodes metastases (LNM) in patients with papillary thyroid cancer (PTC) and coexisting Hashimoto’s thyroiditis (HT).

Patients and methods

This was a retrospective cohort study of patients with PTC and HT who had undergone total thyroidectomy (TT) with central neck dissection (CND) over an 11-year period (between 2002 and 2012). Pathological reports of all eligible patients were reviewed. Multivariable analysis was performed to identify risk factors of LNM.

Results

During the study period, PTC was diagnosed in 130 patients with HT who had undergone TT with CND (F/M ratio?=?110:20; median age, 52.4?±?12.7 years). Multifocal lesions were observed in 28 (21.5 %) patients. LNM were identified in 25 of 28 (89.3 %) patients with multifocal PTC and HT versus 69 of 102 (67.5 %) patients with a solitary focus of PTC and HT (p?=?0.023). In multivariable analysis, multifocal disease was identified as an independent risk factor for LNM (odds ratio, 3.99; 95 % confidence interval, 1.12 to 14.15; p?=?0.033).

Conclusions

Multifocal PTC in patients with HT is associated with an increased risk of LNM. Nevertheless, the clinical importance of this finding needs to be validated in well-designed prospective studies.     

Randomized Controlled Trial of Visualization versus Neuromonitoring of the External Branch of the Superior Laryngeal Nerve during Thyroidectomy

Background  

Injury to the external branch of the superior laryngeal nerve (EBSLN) during thyroidectomy results in a lowered fundamental frequency of the voice and deteriorated voice performance in producing high-frequency sounds. It remains unclear if the use of intraoperative nerve monitoring (IONM) can improve the clinical outcome of thyroidectomy in terms of preserved individual voice performance. This study was designed to test that hypothesis.     

Intrinsic activity and comparative molecular dynamics of buspirone analogues at the 5-HT(1A) receptors

In CNS, the 5-hydroxytryptamine(1A) (5-HT(1A)) receptors exist in two different populations with different behavioural and physiological effects: (1) somatodendritic autoreceptors located pre-synaptically of 5-HT containing neurons and (2) receptors located post-synaptic to 5-HT containing neurons. Clinical studies have shown that 5-HT(1A) partial agonists have anxiolytic properties, while antagonists of pre-synaptical autoreceptors shorten the onset time of selective serotonin reuptake inhibitors (SSRIs). In the present study, the pre- and post-synaptic activity of structural analogues of buspirone was evaluated in animal models. A three dimensional model of the 5-HT(1A) receptor was used to study their interaction modes and helical displacements upon receptor binding. The predicted receptor-ligand interactions indicated similarities in the receptor binding modes for all buspirone analogues, and no clear relationship between receptor contact residues and activity at pre- and post-synaptic receptors. Comparative molecular dynamics (MD) simulations for 650ps indicated that pre-synaptic antagonistic behaviour is connected to large displacements of transmembrane helix (TMH) 7 upon binding, while pre-synaptic agonistic behaviour is connected to large displacements of TMH2 and small displacements of TMH7. Post-synaptic partial agonist behaviour is connected to large displacements of TMH4 and TMH5 upon binding, while post-synaptic antagonists only slightly displace these helices.