Organic nucleating agents and inorganic nanoparticles, as well as their hybrid composites, affect the crystallization temperature and morphology of the monoclinic α-form of isotactic polypropylene ...(iPP). Techniques such as differential scanning calorimetry, hot-stage optical microscopy with cross polars, wide angle X-ray diffraction, and transmission electron microscopy were employed. Nanoparticles of zinc oxide function as efficient supports for 1,3,5-benzene tricarboxylic-(
N-2-methylcyclohexyl)triamine because the temperature at which the maximum rate of iPP crystallization occurs during 10 °C/min cooling from the molten state increases from 111 °C for the pure polymer to 125 °C at low concentrations of this hybrid nucleating agent. In the absence of zinc oxide, 0.06
wt% of this aliphatic triamine recrystallizes near 165 °C and increases the crystallization temperature of iPP by 7 °C, relative to the pure polymer. Fluorinated aromatic triamines, such as 1,3,5-benzene tricaboxylic-(
N-4-fluorophenyl)triamine, are weak nucleating agents that reduce spherulite size in isotactic polypropylene but only increase the crystallization temperature marginally when the polymer is cooled from the molten state. Both micro- and nanoparticles of zinc oxide reduce spherulite size in isotactic polypropylene, but smaller spherulites are observed when the inorganic nanoparticles exhibit dimensions on the order of 40–150 nm relative to micron-size particles. In contrast, 0.06
wt% of the aliphatic triamine in iPP yields a distorted birefringent texture under cross polars that is not spherulitic. Non-spherulitic birefringent textures in iPP are also observed when the aliphatic triamine nucleating agent is coated onto micro- or nanoparticles of zinc oxide. This study demonstrates that the nonisothermal crystallization temperature of isotactic polypropylene increases by an additional 7 °C when an aliphatic triamine is distributed efficiently within the polymeric matrix by coating this nucleating agent onto zinc oxide nanoparticles.
It is now well established that the development and progression of a variety of human malignancies are associated with dysregulated activity of the insulin-like growth factor (IGF) system. In this ...regard, promising drugs have been developed to target the IGF-I receptor or its ligands. These therapies are limited by the development of insulin resistance and compensatory hyperinsulinemia, which in turn, may stimulate cancer growth. Novel therapeutic approaches are, therefore, required. Synthetic PPAR-γ agonists, such as thiazolidinediones (TZDs), are drugs universally used as antidiabetic agents in patients with type 2 diabetes. In addition of acting as insulin sensitizers, PPAR-γ agonists mediate in vitro and in vivo pleiotropic anticancer effects. At least some of these effects appear to be linked with the downregulation of the IGF system, which is induced by the cross-talk of PPAR-γ agonists with multiple components of the IGF system signaling. As hyperinsulinemia is an emerging cancer risk factor, the insulin lowering action of PPAR-γ agonists may be expected to be also beneficial to reduce cancer development and/or progression. In light of these evidences, TZDs or other PPAR-γ agonists may be exploited in those tumors “addicted” to the IGF signaling and/or in tumors occurring in hyperinsulinemic patients.
Functional cross talk between insulin-like growth factor-I (IGF-I) system and estrogen signaling has been largely reported, although the underlying molecular mechanisms remain to be fully elucidated. ...As GPR30/GPER mediates rapid cell responses to estrogens, we evaluated the potential of IGF-I to regulate GPER expression and function in estrogen receptor (ER)α-positive breast (MCF-7) and endometrial (Ishikawa) cancer cells. We found that IGF-I transactivates the GPER promoter sequence and upregulates GPER mRNA and protein levels in both cells types. Similar data were found, at least in part, in carcinoma-associated fibroblasts. The upregulation of GPER expression by IGF-I involved the IGF-IR/PKCδ/ERK/c-fos/AP1 transduction pathway and required ERα, as ascertained by specific pharmacological inhibitors and gene-silencing. In both MCF-7 and Ishikawa cancer cells, the IGF-I-dependent cell migration required GPER and its main target gene CTGF, whereas the IGF-I-induced proliferation required both GPER and cyclin D1. Our data demonstrate that the IGF-I system regulates GPER expression and function, triggering the activation of a signaling network that leads to the migration and proliferation of cancer cells.
ABSTRACT
The wealth of detections of millisecond pulsars (MSPs) in γ-rays by Fermi has spurred searches for these objects among the several unidentified γ-ray sources. Interesting targets are a ...sub-class of binary MSPs, dubbed ‘black widows’ (BWs) and ‘redbacks’ (RBs), which are in orbit with low-mass non-degenerate companions fully or partially ablated by irradiation from the MSP wind. These systems can be easily missed in radio pulsar surveys owing to the eclipse of the radio signal by the intra-binary plasma from the ablated companion star photosphere, making them better targets for multiwavelength observations. We used optical and X-ray data from public data bases to carry out a systematic investigation of all the unidentified γ-ray sources from the Fermi Large Area Telescope Third Source Catalog, which have been pre-selected as likely MSP candidates according to a machine-learning technique analysis. We tested our procedure by recovering known binary BW/RB identifications and searched for new ones, finding two possible candidates. At the same time, we investigated previously proposed BW/RB identifications and we ruled out one of them based upon the updated γ-ray source coordinates.
Non-randomized studies showed that temozolomide (TMZ) achieves an average 10% response rate in heavily pretreated metastatic colorectal cancer (mCRC) patients with promoter methylation of the DNA ...repair gene O6-methylguanine-DNA methyltransferase (MGMT). In this phase II trial, irinotecan and temozolomide (TEMIRI) combination regimen was assessed in irinotecan-sensitive, MGMT methylated/microsatellite stable (MSS) pretreated mCRC patients.
Key inclusion criteria were centrally confirmed MGMT methylation by methylation-specific PCR, MSS mCRC, progression after at least two prior chemotherapy regimens for advanced disease and irinotecan-free interval >3months. TEMIRI (TMZ 150mg/m2 on days 1–5 plus irinotecan 100mg/m2 on days 1, 15 q28 days) was administered for six cycles, followed by maintenance with TMZ. The primary end point was overall response rate (ORR). Exploratory translational analyses included MGMT immunohistochemistry (IHC) and methyl-BEAMing (MB).
Between December 2014 and June 2017, 25 patients were enrolled. The primary end point was met, since six patients achieved a partial response ORR 24%, 95% confidence interval (CI) 11% to 43%. At a median follow-up of 15.6months, median progression-free survival (mPFS) and overall survival (mOS) were 4.4 and 13.8months, respectively. Only four (16%) patients had ≥ grade 3 (CTCAE 4.0) adverse events. All patients whose cancer was MGMT-positive IHC were non-responders. Consistently, patients with MGMT-negative/low tumors had a significantly longer mPFS than others (6.9 versus 2.0months; hazard ratio=0.29, 95% CI 0.02–0.41; P=0.003) and a non-significant trend for longer mOS. MB testing showed similar accuracy.
TEMIRI regimen is a safe and active option in pre-treated, irinotecan-sensitive mCRC patients with MGMT methylation.
Ultraluminous X-ray sources (ULXs) are a class of accreting compact objects with X-ray luminosities above 1039 erg s−1. The ULX population counts several hundred objects but only a fraction are well ...studied. Here we present a detailed analysis of all ULXs hosted in the galaxy NGC 7456. It was observed in X-rays only once in the past (in 2005) by XMM-Newton. but the observation was short and strongly affected by high background. In 2018, we obtained a new, deeper (∼90 ks) XMM-Newton observation that allowed us to perform a detailed characterization of the ULXs hosted in the galaxy. ULX-1 and ULX-2, the two brightest objects (LX ∼ 6−10 × 1039 erg s−1), have spectra that can be described by a model with two thermal components, as often found in ULXs. ULX-1 also shows one order of magnitude in flux variability on short-term timescales (hundreds to thousands of kiloseconds). The other sources (ULX-3 and ULX-4) show flux changes of at least an order of magnitude, and these objects may be candidate transient ULXs, although longer X-ray monitoring or further studies are required to ascribe them to the ULX population. In addition, we found a previously undetected source that might be a new candidate ULX (labeled as ULX-5), with a luminosity of ∼1039 erg s−1 and hard power-law spectral shape, whose nature is still unclear and for which a background active galactic nucleus cannot be excluded. We discuss the properties of all the ULXs in NGC 7456 within the framework of super-Eddington accretion onto stellar-mass compact objects. Although no pulsations were detected, we cannot exclude that the sources host neutron stars.
Long-acting insulin analogs and cancer Sciacca, L.; Vella, V.; Frittitta, L. ...
Nutrition, metabolism, and cardiovascular diseases,
20/May , Letnik:
28, Številka:
5
Journal Article
Recenzirano
Hyperinsulinemia is a recognized risk factor for cancer and plays a major role for the increased cancer incidence in diabetic patients. Whether insulin analogs, and particularly long-acting analogs, ...worsen the pro-cancer effect of excess insulin is still controversial.
In this paper we summarize the biological bases for the potential detrimental effect of long-acting analogs on cancer cells and review the in vitro and in vivo evidence on this issue.
Because of their different molecular structure relative to native insulin, insulin analogs may activate the insulin receptor (IR) and the post receptor pathways differently. Most, but not all, in vitro evidence indicate that long-acting analogs may have a stronger mitogenic potency than insulin on cancer cells. Notably insulin glargine, the most studied long-acting analog, also has a higher affinity for the insulin-like growth factor (IGF)-1 receptor, a potent growth mediator. In vitro observations, however, may not reflect what occurs in vivo when analogs are metabolized to derivatives with a different mitogenic activity. Clinical studies, mostly retrospective and predominantly concerning glargine, provide contrasting results. The only perspective trial found no cancer increase in patients treated with glargine. All these studies, however, have severe weaknesses because of the insufficient evaluation of important factors such as dose administered, length of exposure, patient follow-up duration and site-specific cancer investigation. Moreover, whether cancer promotion is a long-acting analog class characteristic or a specific effect of a single agent is not clear.
In conclusion the carcinogenic risk of long-acting analogs, and specifically glargine, can be neither confirmed nor excluded. A personalized and shared decision, considering all the individual risk factors (metabolic and non-metabolic), is the suggestion for the clinician.
•Hyperinsulinemia is a recognized risk factor for cancer. Whether or not insulin analogs increase this risk is debated.•Long-acting insulin analogs (particularly glargine) have an increased growth promoting effect on cancer cells in vitro.•Most clinical studies, that have severe limitations, found no cancer increase in patients treated with insulin analogs.•A causal association between insulin analogs and cancer is neither demonstrated nor excluded.
Three types of graphene oxide/silver nanoparticles (GO/AgNPs) composite membranes were prepared to investigate size-effect of AgNPs on nanofiltration ability. The size of AgNPs was 8, 20, and 33 nm, ...which was characterized by UV-visible spectroscopy and transmission electron microscopy. The morphology and structure of GO and GO/AgNPs composite membranes were characterized by atomic force microscopy, scanning electron microscopy, and X-ray diffraction. The filtration performance of membranes were evaluated on a dead-end filtration device. When the size of AgNPs is 20 nm, the GO/AgNPs composite membrane has the highest water flux (106.1 L m
h
bar
) and rejection of Rhodamine B (RhB) (97.73%) among three types of composite membranes. The effect of feed concentration of dye solution and the flux of common solvent was also investigated. The mechanism was discussed, which demonstrated that both interlaying spacing and defect size influence the filtration ability of membrane, which is instructive to future study.
With the growing needs for flexible fluorescence emission materials, emission fibers and related wearable fabrics with bright emission properties have become key factors for wearable applications. In ...this article, novel cuboid-like crystals of Eu3+ complexes were generated. Except for light-energy-harvesting ligands of thenoyltrifluoroacetone (TTA) and 1,10-phenanthroline hydrate (Phen), the crystal structures were adjusted by other functional amphiphilic molecules. Not only does ETPC-SA, adjusted by stearic acid, have a regular cuboid-like crystal with a size of about 2 μm size, but it also generates the best photon emission property, with a fluorescence quantum yield of 98.4% fluorescence quantum yield in this report. Furthermore, we succeeded in producing novel fluorescent fibers by mini-twin-screw extrusion, and it was easy to form bright red fabrics, which are equipped with strong fluorescence intensity, flexibility, and a smooth hand feeling, with the normal fabricating method in our work. It is worth noting that ETPC-HQ fibers, which carry a crystal complex adjusted by hydroquinone, possess the lowest quantum yield but have the longest average fluorescence lifetime of 1259 µs. This result means that a low-density polyethylene (LDPE) matrix could make excited electrons stand in the excited state for a relatively long time when adjusted by hydroquinone, so as to increase the afterglow property of fluorescent fibers.
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