The aim the present work was to produce carbon foams with as different as possible porous structures but with similar composition and carbon texture for studying precisely the influence of different ...structural parameters such as density, cell size or interconnectivity on the physical properties of these foams. Over 60 different cellular carbon foams were obtained by pyrolysis of phenolic-furanic rigid foams, whose structure was tailored through some changes in the formulations. The structures of all of these materials were thoroughly characterised through scanning electron microscopy (SEM) and X-Ray microtomography. Both methods proved to give very consistent results, justifying the use of the simpler one, i.e., SEM. Very broad ranges of bulk densities (0.015≤d≤0.333gcm−3) and of average cell diameters (100≤D≤5000μm) were obtained. Despite these very different morphologies, elemental analysis, helium pycnometry and Raman spectroscopy studies showed that the carbon constituting the foams can be considered as identical. The results presented here should be used as a basis for the most thorough and extensive studies of physical properties of vitreous carbon foams.
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Endocrine therapy of breast cancer Lumachi, F; Luisetto, G; Basso, S M M ...
Current medicinal chemistry,
02/2011, Letnik:
18, Številka:
4
Journal Article
Recenzirano
Breast cancer remains one of the first leading causes of death in women, and currently endocrine treatment is of major therapeutic value in patients with estrogen-receptor positive tumors. Selective ...estrogen-receptor modulators (SERMs), such as tamoxifen and raloxifene, aromatase inhibitors, and GnRH agonists are the drugs of choice. Tamoxifen, a partial nonsteroidal estrogen agonist, is a type II competitive inhibitor of estradiol at its receptor, and the prototype of SERMs. Aromatase inhibitors significantly lower serum estradiol concentration in postmenopausal patients, having no detectable effects on adrenocortical steroids formation, while GnRH agonists suppress ovarian function, inducing a menopause-like condition in premenopausal women. Endocrine therapy has generally a relatively low morbidity, leading to a significant reduction of mortality for breast cancer. The aim of chemoprevention is to interfere early with the process of carcinogenesis, reducing the risk of cancer development. As preventive agents, raloxifene and tamoxifene are equivalent, while raloxifene has more potent antiresorptive effects in postmenopausal osteoporosis. Endocrine treatment is usually considered a standard choice for patients with estrogen-receptor positive cancers and non-life-threatening advanced disease, or for older patients unfit for aggressive chemotherapy regimens. Several therapeutic protocols used in patients with breast cancer are associated with bone loss, which may lead to an increased risk of fracture. Bisphosphonates are the drugs of choice to treat such a drug-induced bone disease. The aim of this review is to outline current understanding on endocrine therapy of breast cancer.
Glioblastoma is the most frequent brain tumor in adults and is the most lethal form of human cancer. Despite the improvements in treatments, survival of patients remains poor. In order to identify ...microRNAs (miRs) involved in glioma tumorigenesis, we evaluated, by a miRarray, differential expression of miRs in the tumorigenic glioma LN-18, LN-229 and U87MG cells compared with the non-tumorigenic T98G cells. Among different miRs we focused our attention on miR-221 and -222. We demonstrated the presence of a binding site for these two miRs in the 3' untranslated region of the protein tyrosine phosphatase μ (PTPμ). Previous studies indicated that PTPμ suppresses cell migration and is downregulated in glioblastoma. Significantly, we found that miR-221 and -222 overexpression induced a downregulation of PTPμ as analyzed by both western blot and real-time PCR. Furthermore, miR-222 and -221 induced an increase in cell migration and growth in soft agar in glioma cells. Interestingly, the re-expression of PTPμ gene was able to revert the miR-222 and -221 effects on cell migration. Furthermore, we found an inverse correlation between miR-221 and -222 and PTPμ in human glioma cancer samples. In conclusion, our results suggest that miR-221 and -222 regulate glioma tumorigenesis at least in part through the control of PTPμ protein expression.
The integrated stress response (ISR) attenuates the rate of protein synthesis while inducing expression of stress proteins in cells. Various insults activate kinases that phosphorylate the GTPase ...eIF2 leading to inhibition of its exchange factor eIF2B. Vanishing White Matter (VWM) is a neurological disease caused by eIF2B mutations that, like phosphorylated eIF2, reduce its activity. We show that introduction of a human VWM mutation into mice leads to persistent ISR induction in the central nervous system. ISR activation precedes myelin loss and development of motor deficits. Remarkably, long-term treatment with a small molecule eIF2B activator, 2BAct, prevents all measures of pathology and normalizes the transcriptome and proteome of VWM mice. 2BAct stimulates the remaining activity of mutant eIF2B complex in vivo, abrogating the maladaptive stress response. Thus, 2BAct-like molecules may provide a promising therapeutic approach for VWM and provide relief from chronic ISR induction in a variety of disease contexts.
Pine bark tannin foams were prepared for the first time. The high reactivity of pine tannins in relation to other tannins induced the change in the tannin foam formulations in order to coordinate ...foam resin hardening, reaction exotherm and solvent blowing allowing the formation of a rigid foam. Pine tannin foams with and without formaldehyde were prepared. Their characteristics were tested as regards stress–strain curves, thermal conductivity, Young's modulus, compression strength, densification, densification rate and energy absorbed under compression. Mostly, properties the pine tannin foams with formaldehyde have properties similar to mimosa tannin foams, in some cases slightly lower and in others slightly higher. Pine tannin foams without formaldehyde showed lower mechanical strength and more elastic behaviour. Display omitted
► Pine bark tannin foams were prepared with and without formaldehyde for the first time. ► High reactivity tannin induced change in foam formulations to coordinate foam resin hardening, reaction exotherm and solvent blowing. ► Stress–strain curves, thermal conductivity, E-modulus, compression strength and energy adsorbed, densification and its rate, were tested. ► Pine tannin foams have properties similar to mimosa tannin foams. ► Pine tannin foams without formaldehyde showed lower mechanical strength and more elastic behaviour.
Pine bark tannin foams were prepared for the first time. The high reactivity of pine tannins in relation to other tannins induced the change in the tannin foam formulations in order to coordinate foam resin hardening, reaction exotherm and solvent blowing allowing the formation of a rigid foam. Pine tannin foams with and without formaldehyde were prepared. Their characteristics were tested as regards stress–strain curves, thermal conductivity, Young's modulus, compression strength, densification, densification rate and energy absorbed under compression. Mostly, properties the pine tannin foams with formaldehyde have properties similar to mimosa tannin foams, in some cases slightly lower and in others slightly higher. Pine tannin foams without formaldehyde showed lower mechanical strength and more elastic behaviour.
Cellular vitreous carbon (CVC) foams have been prepared from tannin-based resin modified by isocyanates of different natures, added in different amounts, and according to different mixing methods. We ...show that low amounts of isocyanate allow considerable changes in the porous structures of the resultant CVC foams. The latter are now more homogeneous, present thicker cell walls, porous struts, and their cells are less connected with each others. Additionally, average cell size and density can be independently controlled, whereas they were intimately related to each other in the first generation of tannin-based CVC foams. The accessible range of bulk density is also much wider (0.04–0.3gcm−3) than before. CVC foams modified with isocyanate present extremely low thermal conductivity (less than 0.1Wm−1K−1), whereas their mechanical properties have been significantly improved (up to 8.4 and 140MPa for compressive strength and elastic modulus, respectively). Modification by isocyanate thus opened a new route towards CVC foams of controlled porosity and properties.
Background
Endocrine neoplasms are generally slow-growing tumors that can show hormonal activity and give metastases. In most cases they are benign and clearly malignant forms are easy to diagnose. ...However, borderline forms may occur and be, for the pathologists, very difficult to classify. In these cases, there is a strong need to identify factors that may aid. Official classification systems for endocrine neoplasms are based on the evaluation of proliferation and, in most cases, they rely on mitotic count. In support, the study of Ki67 is carried out which, however, has not yet been included in any official classification system, except for neuroendocrine neoplasms of the gastro-entero-pancreatic tract.
Purpose
The aim of the present study was to investigate the proven or unproven role of Ki67 in endocrine neoplasms, in different districts, in order to bring to light the substantial differences, in terms of proliferation, existing between neoplasms so similar, but at the same time, so different.
Methods
A thorough search of English language literature was performed, looking for articles concerning Ki67 in five endocrine neoplasms (pituitary adenomas, thyroid neoplasms, adrenocortical neoplasms, pheochromocytomas and paragangliomas).
Results
From 2170, 236 articles were selected and it was seen that the endocrine neoplasm in which Ki67 was most studied was the pituitary, where it still shows a controversial role. In other neoplasms different roles were identified.
Conclusion
The pathologist should be aware of the contribution that this proliferative marker can give to the diagnosis and, sometimes, to the therapy selection, for the clinician.
Estrogen receptor (ER) expression is the main indicator of potential responses to endocrine therapy (ET), and approximately 70% of human breast cancers (BCs) are hormone-dependent and ER-positive. ...The introduction of adjuvant systemic therapy led to a significant improvement in post-surgical survival and a reduction in disease relapse, especially in women with early BC and those with ER+ tumors, who may receive ET alone or in combination with cytotoxic therapy. Adjuvant ET currently consists of (i) ovarian suppression, (ii) selective estrogen receptor modulators (SERMs) and down-regulators, and (iii) aromatase inhibitors (AIs). In patients with ER+ tumors pharmacologic ovary suppression with gonadotropin-releasing hormone agonists in combination with standard adjuvant therapy is generally more effective than adjuvant chemotherapy alone. Tamoxifen is the best established SERM, has favorable effects on BC control and bone metabolism, but also has adverse effects due to its estrogenic activity in other tissues. For these reasons, other SERMs have been developed. Fulvestrant is an ER down-regulator with several potential advantages over SERMs, including a 100-fold increase in its affinity for ER compared with tamoxifen and no estrogen-like activity in the uterus. The inhibition of the aromatase system with third-generation AIs is associated with improved survival in patients with advanced BC compared with SERMs. In postmenopausal patients with ER+ BC adjuvant treatment with AIs should be performed, either as sequential treatment after tamoxifen or as upfront therapy. Studies evaluating the role of AIs as first-line therapy are ongoing and the results are encouraging.
Knowledge without awareness, or implicit knowledge, influences a variety of behaviors. It is unknown however, whether implicit knowledge of statistical structure informs visual perceptual decisions ...or whether explicit knowledge of statistical probabilities is required. Here, we measured visual decision-making performance using a novel task in which humans reported the orientation of two differently colored translational Glass patterns; each color associated with different orientation probabilities. The task design allowed us to assess participants' ability to learn and use a general orientation prior as well as a color specific feature prior. Classifying decision-makers based on a questionnaire revealed that both implicit and explicit learners implemented a general orientation bias by adjusting the starting point of evidence accumulation in the drift diffusion model framework. Explicit learners additionally adjusted the drift rate offset. When subjects implemented a stimulus specific bias, they did so by adjusting primarily the drift rate offset. We conclude that humans can learn priors implicitly for perceptual decision-making and depending on awareness implement the priors using different mechanisms.
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