Uterine cancer restaging according to the updated 2023 FIGO Guidelines does not uniformly affect prognosis: An institutional retrospective cohort study.

OBJECTIVE: Efforts have been made to better risk stratify patients given the rise in incidence of endometrial cancer (EC). The 2023 FIGO staging now incorporates histologic subtype and molecular classification into determination of EC stage. We sought to elucidate if the new staging system demonstrated prognostic differences compared to the 2009 staging system. METHODS: A retrospective chart review was performed on women treated for EC at our institution from September 2013 to May 2023 and combined with the publicly available TCGA Nature 2013 dataset. Detailed clinical information was captured. Patients were restaged according to the 2023 guidelines. Survival estimates were obtained using Kaplan-Meier method, and the log-rank test was used to compare survival curves for progression-free survival (PFS). RESULTS: 919 patients were included in our analysis. The datasets were comparable regarding histologic grade, stage, and age at diagnosis. 175 (31.5%) of patients in the institution dataset and 115 (31.6%) patients in the TCGA dataset experienced a stage change. Most patients whose stage changed were upstaged (275/290; 94.8%). 3-year PFS estimates for stage IA patients with no stage change versus those upstaged were 92.3% (95% CI: 87.2, 95.4) v. 72.0% (95% CI: 68.4, 84.9), p = 0.002. No significant differences in survival difference were seen in other stage subsets. CONCLUSION: Modest survival differences exist in patients with EC originally staged as IA who underwent upstaging. No significant survival difference is observed in patients who are restaged to stage II or III subsets. Improved risk stratification is needed in assessing prognosis and adjuvant therapy for patients with endometrial cancer.

From plasma to nanoparticles: optical and particle emission of a spark discharge generator.

The increased demand for high purity nanoparticles (NPs) of defined geometry necessitates the continuous development of generation routes. One of the most promising physical techniques for producing metal, semiconductor or alloy NPs in the gas phase is spark discharge NP generation. The technique has a great potential for up-scaling without altering the particles. Despite the simplicity of the setup, the formation of NPs in a spark discharge takes place via complex multi-scale processes, which greatly hinders the investigation via conventional NP measurement techniques. In the present work, time-resolved optical emission spectroscopy (OES) was used to provide information on the species present in the spark from as early as approximately 100 ns after the initiation of the discharge. We demonstrate that operando emission spectroscopy can deliver valuable insights into NP formation. The emission spectra of the spark are used to identify, among others, the main stages of material erosion and to calculate the quenching rate of the generated metal vapour. We demonstrate that the alteration of key control parameters, that are typically used to optimize NP generation, clearly affect the emission spectra. We report for Cu and Au NPs that the intensity of spectral lines emitted by metal atoms levels off when spark energy is increased above an energy threshold, suggesting that the maximum concentration of metal vapour produced in the generator is limited. This explains the size variation of the generated NPs. We report a strong correlation between the optical and particle emission of the spark discharge generator, which demonstrate the suitability of OES as a valuable characterization tool that will allow for the more deliberate optimization of spark-based NP generation.

Thermoresponsive latexes for fragrance encapsulation and release.

OBJECTIVE: To synthesize cross-linked latex particles protecting the encapsulated fragrance at ambient temperatures and facilitating the release of cargo at the temperature of the surface of the skin that varies in different regions of the body between 33.5 and 36.9°C. Poly(stearyl acrylate) (PSA), a polymer with long crystallizable alkyl side chains (undergoes order-disorder transitions at 45°C), was chosen as the main component of the polymer particles. As a result, new thermoresponsive polymer particles for fragrance encapsulation were synthesized and characterized, including assessing the performance of particles in triggered release by elevated temperature. METHODS: To obtain network domains of various crystallinity, stearyl acrylate was copolymerized with dipropylene glycol acrylate caprylate (DGAC) (comonomer) in the presence of a dipropylene glycol diacrylate sebacate (cross-linker) using the miniemulsion process. Comonomers and a cross-linker were mixed directly in a fragrance during polymerization. Fragrance release was evaluated at 25, 31, 35 and 39°C to demonstrate a new material potential in personal/health care skin-related applications. RESULTS: Particles protect the fragrance from evaporation at 25°C. The fragrance release rate gradually increases at 31, 35 and 39°C. Two slopes were found on release plots. The first slope corresponds to a rapid fragrance release. The second slope indicates a subsequent reduction in the release rate. CONCLUSION: Crystalline-to-amorphous transition of PSA triggers the release of fragrances from cross-linked latex particles at elevated temperatures. The presence of the encapsulated fragrance, as well as the inclusion of amorphous fragments in the polymer network, reduces the particle crystallinity and enhances the release. Release profiles can be tuned by temperature and controlled by the amount of loaded fragrance and the ratio of comonomers in the feed mixture.

Amphiphilic invertible polymers for adsolubilization on hydrophilic and hydrophobized silica nanoparticles.

Adsolubilization of poorly water-soluble 2-naphthol into amphiphilic invertible polymers (AIPs) has been successfully performed on hydrophilic and hydrophobized silica nanoparticles. The polymers adsolubilize molecules of sparingly water-soluble 2-naphthol into the adsorbed layer on both substrates. AIP macromolecules show different surface activity depending on length of the hydrophobic fragment in macromolecules. Different AIP fragments are responsible for polymer adsorption on hydrophilic and hydrophobized silica. It is expected that mainly AIP hydrophobic fragments interact with 2-naphthol molecules and facilitate adsolubilization. The amount of adsolubilized 2-naphthol does not depend on substrate nature and length of the hydrophobic fragment in polymer. It is primarily regulated by the total length of the adsorbed macromolecules.

MDR1 (C3435T) polymorphism: relation to the risk of breast cancer and therapeutic outcome.

P-glycoprotein (PGP), the product of the MDR1 gene, is a transmembrane active efflux pump for a variety of carcinogens and cytostatics. It has been suggested that MDR1 polymorphisms contribute to the variability in cancer risk and therapeutic outcome. We examined the relevance of C3435T polymorphism in relation to breast cancer susceptibility, clinical and pathological characteristics of breast carcinoma, the therapeutic response and hematologic toxicities after anthracycline-based chemotherapy. A significant association between allele frequencies and histological type, stage and histological grade was observed (P=0.024, 0.014, 0.006, respectively, chi(2)-test or Fisher's exact test). We also found significantly higher (P=0.019, chi(2)-test) T allele frequency in breast cancer patients (n=221) than in controls (n=113). A significantly enhanced therapeutic outcome after neoadjuvant therapy (n=38; P=0.021, Fisher's exact test) and longer time to progression after anthracycline-based chemotherapy (n=102; P=0.049, log-rank test) were observed in CC homozygotes. However, no significant association between hematologic toxicities and C3435T polymorphism was detectable.

[Polymorphism of gene p53 and apoptosis in patients with malignant lung disease--our observation]. / Polymorfizmus génu p 53 a apoptóza u pacientov s nádormi pl'úc--nase sledovanie.

BACKGROUND: Many proved alterations in genoms of cells are said to be related to tumorigenesis. Apoptosis--a "programmed" death of cell, which has different morphology from necrosis, is one of the control mechanisms of cell division and participates in tumorigenesis. METHODS AND MATERIAL: The authors present their results of analysis of the relation between genetic polymorphism of the p53 gene and the level of apopotosis in patients with confirmed malignant lung disease. Comparison of genetic polymorphism of the p53 gene in patients with the healthy group showed that allocation of BstUI A2 and MspI A1 alleles was significantly related to lung cancer. The apoptosis of peripheral lymphocytes was significantly increased in lung cancer patients. The highest increase of apoptosis in non-small cell lung cancer (NSCLC) group was found in adenocarcinomas. The level of apoptosis was also studied in correlation to polymorphism of the p53 gen. Substantially higher percentage of apoptotic cells was detected in BstUI 2/2 and MspI 2/2 homozygotes. In response to operation a distinctive increase of apoptosis in the first and second postoperative day was recorded. Therefore a lymphocyte count in peripheral blood was also monitored. The lymphocyte count in patients that underwent the operation proved a decrease in absolute and relative values. CONCLUSION: Observation of known genetic polymorphisms indicates the risk of malignant disease. Together with the analysis of level of apoptosis it may add to complexity of the nature of malignant disease or serve as determinants of its prognosis.

Mechanism of silver ion reduction in concentrated solutions of amphiphilic invertible polyesters in nonpolar solvent at room temperature.

Fast formation and efficient stabilization of silver nanoparticles from [Ag(NH3)2]OH are achieved in concentrated nonpolar solutions of amphiphilic invertible polyesters based on poly(ethylene oxide) (PEO) and aliphatic dicarboxylic acids. Surface-modified silver nanoparticles able to be dispersed in both a polar and nonpolar medium are developed in the form of a ready-to-use colloidal solution with an enhanced silver concentration. The PEO fragments of polyesters form cavities (also called pseudo-crown ester structures) that can bind metal ions. The reduction of bound metal ions proceeds via oxidation of polyoxyethylene fragments. No chemical reducing agents are necessary in this approach. The polyesters act simultaneously as an efficient reducing agent and stabilizer. The main focus of the present research is to clarify the chemical mechanism of silver ion reduction in amphiphilic polyester solutions. A one-electron reduction mechanism is proposed to explain the formation of silver nanoparticles. The effect of the poly(ethylene oxide) fragment length and the polyester concentration are explored by examining several amphiphilic polyesters.

Surface activity of new invertible amphiphilic polyesters based on poly(ethylene glycol) and aliphatic dicarboxylic acids.

The surface active properties of aqueous solutions of invertible amphiphilic alternated polyesters differing by hydrophilic-lipophilic balance (HLB) and molecular weight have been determined over the wide concentration range. The polyesters are based on poly(ethylene glycol) (PEG) of two molecular weights and aliphatic dicarboxylic acids (decanedioic and dodecanedioic). The surface activity of the polyesters and their ability to form micellar assemblies (which was recently shown for organic solvents) has been confirmed in water. The central role of the balance of hydrophilic to hydrophobic groups ratio in the formation of polymeric arrangements having hydrophobic pockets and external hydrophilic shell has been shown. The effect of molecular weight has been found considerable as well. Two changes in slope have been observed for the more hydrophobic polyesters in the surface tension vs log concentration curve. The change at low concentration is believed to originate from the formation of polyester assemblies with a hydrophobic interior and hydrophilic exterior due to the interaction of hydrophobic fragments and macromolecular flexibility. The higher concentration region exhibits behavior consistent with a cmc, which was confirmed by additional dye solubilization experiments. Molecular structure of the polyester micelles is determined by the solubilization of a solvatochromic dye. The experiment confirmed that micellization of polyesters is accompanied by the association of more hydrophobic (aliphatic) constituents forming the micelle interior. The hydrophilic fragments (ethylene oxide groups) are involved in the formation of micelle exterior.

Study of amphiphilic polyester micelles by hyper-rayleigh scattering: invertibility and phase transfer.

For the first time, hyper-Rayleigh scattering (HRS) of invertible polymeric micellar structures has been measured. HRS measurements on amphiphilic invertible polyesters with alternating hydrophilic and hydrophobic fragments were carried out in solvents of differing polarity. The observed strong variation of the HRS signals is attributed to the switching behavior of the polyester micelles in the different solvents. The hyperpolarizabilities and the size of the micelles increased with decreasing polarity of the solvent. Observing the dynamics of the solubilization of an insoluble dye (malachite green) by the invertible polyester in toluene confirmed the possibility to reveal conformational changes in polyester macromolecules by HRS. In contrast to UV measurements which showed a continuous increase in absorbance and indicated overall solubilization of the dye, the HRS signals decreased after approaching a maximum value. The decrease of the HRS signals is attributed to the change of dye molecules' orientation within the micelles due to the change of polymeric conformation in toluene. The results have shown that HRS is sensitive to reorientation and ordering of the macromolecules and might become a powerful tool for studying polymer micellar structures as well as phase transfer processes at the nanoscale.

An effective way to stabilize colloidal particles dispersed in polar and nonpolar media.

This article offers a new approach to building up self-adjustable invertible polymer coatings at solid surfaces. The approach is based on a two-step process. In the first step, the surface of dispersed TiO2 has been functionalized with the aid of toluene diisocyanate (TDI) as a coupling agent. In the second step, the chains of amphiphilic oligoester have been covalently grafted to the titanium dioxide surface functionalized with isocyanate groups. It is shown that the titania modified in this way can form stable suspensions in both polar (water) and nonpolar (toluene) media. Multiple redispersion cycles show the ability of the modified titanium dioxide particles, after their removal from one type of dispersion and consequent drying, to be redispersed in dispersing media strongly differing by polarity from the previous.

Design of a new invertible polymer coating on a solid surface and its effect on dispersion colloidal stability.

This article presents a new approach to building up self-adjustable invertible polymer coatings at solid surfaces. The approach is based on a two-step process. In the first step, the surface of dispersed TiO2 or silicon wafers was functionalized with the aid of a reactive copolymer, viz., poly(styrene-alt-maleic anhydride) (PSM), to which, in the second step, the chains of amphiphilic oligoester have been tethered. The latter contains both hydrophilic poly(ethylene glycol) and hydrophobic aliphatic dibasic acid moieties being alternately distributed along the oligomer chains. It is shown that the titania modified in this way can form stable suspensions in both polar (water) and nonpolar (toluene) media. Moreover, multiple drying/redispersion cycles demonstrate the ability of the modified titania particles, after their removal from one type of dispersion and consequent drying, to be redispersed in dispersing media strongly differing by polarity from that of the previous medium. An environmentally induced switching of the surface properties has been observed via the measurement of the wetting contact angles and scanning force microscopy (SFM) of silicon wafers covered by PSM with tethered oligoester chains. These experiments give strong support for the predicted capability of such polymer coatings to switch their environmental appearance (i.e., to behave as a self-adjustable invertible interface because of the ability of the tethered amphiphilic oligoester chains to change their conformations in response to environmental changes in such a manner so as to adapt and enhance their compatibility with the surrounding media).

[Apoptosis, tumor phenotype and pathogenesis of malignant tumors]. / Apoptóza, nádorový fenotyp a patogenéza zhubných nádorov.

Integrity of multicellular organisms is maintained by balance between cell proliferation and programmed cell death (apoptosis). Apoptosis is programmed cell death by regulated active process characterized by specific morphological and biochemical changes, whereas necrosis is a passive and genetically uncontrolled process followed by an inflammatory reaction of surrounding tissue. Suppression of apoptosis may contribute to the development of malignant tumours by means of accumulation of continuously proliferating cells and disruption of elimination of genetically altered cells with increasing malignant potential. Cell proliferation, differentiation and apoptosis are regulated by p16-cyclin D1-CDK4-Rb and p19ARF-p53-p21WAF1 pathways, which interact through multifunctional genes Rb and p53. Malignant tumours result from an accumulation of mutations of oncogenes, tumour-suppressor genes, pro-apoptotic and anti-apoptotic genes or from functional alterations of protein products of these genes as well. That results in dysregulation of the cell cycle and apoptosis and in the development of other signs of tumour phenotype (chromosomal instability, disruption of DNA repair, disruption of cell-cell communications and interactions between cells and extracellular matrix, suppression of the cell differentiation and replicative senescence, angiogenesis and changes in cell motile activity). Alteration of apoptosis, and/or genes involved in its regulation, is expressed in most manifestations of tumour phenotype. Thus, alteration of apoptosis strongly affects biological properties of malignant tumours and efficacy of their multimodal therapy. Present-day multimodal therapy of malignant tumours is specifically aimed at promoting the rate of apoptosis within tumours.

[Apoptosis in T-lymphocytes and its significance]. / Apoptóza T-lymfocytov a jej význam.

Apoptosis is an integral process of the immune system development and existence. Due to the ability of lymphocytes to follow the apoptotic pathway a very negative effect--the escape of tumor cells population from the immune system control is observed. Multiplying malignant cells during the tumor progression cause the synergic effect of tumor cells apoptosis blocation and unfavourable T-lymphocytes apoptosis induction. The lymphocyte cells apoptosis can be induced by the tumor produced substances as well as the receptor spectrum exprimated by the tumor cells. Physical and chemical anti-cancer therapy causing the non-selective apoptosis induction also contributes substantially to the immune system weakening. Fas-receptor (FasR) is constitutionally expressed on the activated T-lymphocyte surface. The common sign of the lung, colorectal, breast and other carcinomas is the presence of the surfacial Fas-ligand (FasL). During the infiltration process of tumor by the lymphocytes the FasR/FasL interaction is present, which is probably the most effective trigger mechanism of the T cells apoptosis. The contact of T-lymphocytes and tumor cells for the active antitumor immunity is inevitable. The apoptotic pathways modulation of T-lymphocytes provides a space for FasR/FasL induction influence and thus the anticancer immunity efficiency determination.

Allelic and haplotype frequencies of the p53 polymorphisms in brain tumor patients.

The polymorphisms of the tumor suppressor gene p53 in exon 4 (p53 BstUI) and in intron 6 (p53 MspI) have been suggested to be associated with the genetically determined susceptibility in diverse types of human cancer. In our hospital-based case-control study, we examined the allele and genotype incidence of these polymorphisms as well as their haplotype combinations in 60 brain tumor patients (27 males and 33 females) and 183 controls without malignancies. The genotype characteristics were determined by the PCR-based RFLP method using DNA extracted from peripheral blood. In this study we show that the p53 BstUI and the p53 MspI polymorphisms are not associated with increased risk of brain tumors. Thus, we conclude that the p53 BstUI and the p53 MspI polymorphic sites within the tumor suppressor gene p53 do not represent genetic determinants of susceptibility to brain tumors.

Changes of gastric lipase activity after ethanol and indomethacin administration: influence of pretreatment with allopurinol, pentoxifylline and L-DOPA.

Gastric lipase (GL) plays an important role in emulsification and digestion of food fat. Lipids are components of the hydrophobic mucus and mucosa barrier. Damage of the gastric mucosa may therefore be related to changes in the lipid content and GL activity. In the present paper, we studied the effect of administration of a single dose of 96 % ethanol (E) and indomethacin 20 mg x kg(-1) (IND) on the activity of GL and on the concentrations of nonesterified fatty acids (NEFA) and triacylglycerols (TG) in the gastric mucosa of rats. Furthermore, we studied how these changes are affected by allopurinol (ALO), pentoxifylline (PX) and L-DOPA pretreatment 30 min before administration of E or IND. The effect of sialoadenectomy (SA) on these parameters was also evaluated. We found: 1) significant (p < 0.01) inhibition of GL activity after administration of E and IND and also ALO, as well as after pretreatment with ALO before E and PX before IND. L-DOPA administered alone stimulated GL activity, but its administration before IND significantly (p < 0.01) inhibited this enzymatic activity. GL activity was decreased to the threshold values in SA rats and after administration of E to SA animals. 2) NEFA concentrations were decreased after E and increased significantly (p < 0.01) after IND administration. A marked significant (p < 0.01) decrease in NEFA was found after PX and L-DOPA administration. The administration of ALO also lowered the concentration of NEFA. Pretreatment by drugs before E and IND resulted in a significant increase of NEFA in comparison with the drugs given alone (p < 0.05 for ALO + E; p < 0.01 for PX + IND). 3) TG were also decreased in all experimental groups in comparison with the control group, i.e. after E and IND, after ALO and SA and also after pretreatment by ALO before E. The concentration of TG decreased after PX, significantly (p < 0.05) after L-DOPA and after pretreatment by PX before IND. Pretreatment by ALO before E and L-DOPA before IND resulted in the increase of TG in comparison with drugs alone. Thus, these results suggest certain protective effect of pretreatment with ALO, PX and L-DOPA against the E- and IND-induced decrease in NEFA and TG during injury of the gastric mucosa. On the other hand, inhibition of GL activity was also apparent after administration of these drugs before E and IND, which suggest presence of a persisting impairment of lipid digestion in the stomach.

Germ line polymorphisms of the tumor suppressor gene p53 and lung cancer.

Two p53 variable sites (BstUI and MspI SNPs in exon 4 and intron 6, respectively) and their haplotype combinations were studied in 109 patients (84 males and 25 females) with lung cancer and 113 healthy controls from the region of Eastern Slovakia. There were no differences found between lung cancer patients and controls carrying the distribution of p53 BstUI and MspI alleles. However, the genotype distribution showed a significantly higher proportion of MspI heterozygotes in lung cancer patients (P=0.048, OR 1.83, 95% CI 1.00-3.34) than in controls. The analysis based on haplotype frequencies showed the presence of BstUI-MspI 2-1 haplotype in cancer patients (5.4%) in contrast to the absence of this haplotype in healthy controls. The results of this study suggest that the p53 MspI polymorphism may modify the susceptibility to lung cancer as a single factor rather than in combination with BstUI polymorphism.

Polymorphism of the p53 gene within the codon 72 in lung cancer patients.

We tested the codon 72 single nucleotide polymorphism (SNP) of the tumor suppressor gene p53 for association with lung cancer. In our hospital-based case-control study, 168 lung cancer patients (134 males and 34 females) and 148 controls without malignant diseases were recruited. The genotype characteristics were determined by PCR-based RFLP method using DNA extracted from peripheral blood. Only in lung cancer patients but not in the controls we found both significant decrease of A1 allele of the p53 codon 72 (p=0.024, OR 0.56, 95% CI 0.43-0.72) and A1/A1 homozygous genotype (p=0.006, OR 0.27,95% CI 0.15-0.51). The results of this study suggest a protective effect of A1 allele against lung cancer.

Consequences of reducing nonresponse in a national telephone survey.

Critics of public opinion polls often claim that methodological shortcuts taken to collect timely data produce biased results. This study compares two random digit dial national telephone surveys that used identical questionnaires but very different levels of effort: a "Standard" survey conducted over a 5-day period that used a sample of adults who were home when the interviewer called, and a "Rigorous" survey conducted over an 8-week period that used random selection from among all adult household members. Response rates, computed according to AAPOR guidelines, were 60.6 percent for the Rigorous and 36.0 percent for the Standard study. Nonetheless, the two surveys produced similar results. Across 91 comparisons, no difference exceeded 9 percentage points, and the average difference was about 2 percentage points. Most of the statistically significant differences were among demographic items. Very few significant differences were found on attention to media and engagement in politics, social trust and connectedness, and most social and political attitudes, including even those toward surveys.

[Biochemical changes in apoptosis and methods for their determination (review)]. / Niektoré biochemické zmeny pri apoptóze a metódy ich stanovenia (aktuálny prehl'ad).

Apoptosis or programmed cell death is a physiological process which occurs at different biological states as well as at disease process. Morphologically it is characterized by the chromatine condensation and other changes with preserved integrity of plasmatic membrane. The major and most frequently studied biochemical characteristic of apoptosis is a DNA fragmentation. In our paper attention is directed to the early biochemical changes in cell membranes, i.g., the externalization of phosphatidylserine, hydrolysis of sphingomyeline on the ceramide and activation of phospholipases especially phospholipase A2. In one part we described the changes of cysteine proteases (caspases), which play a key role in the execution of apoptosis. These biochemical changes are associated with ceramide signalization of apoptosis. Briefly are presented also some dates about apoptosis induction with reactive oxygen radicals and the role of the arachidonic acid metabolites in this process. We consider the investigation and determination of these changes as important parameters of apoptosis at some diseases, e.g., cancer or degenerative diseases, and of their treatment.

Reciprocal adaptive response of human peripheral lymphocytes induced by bleomycine or gamma rays.

The adaptive response and reciprocal adaptive response induced in vitro by exposure to low doses of gamma rays (0.05 Gy) or bleomycin (0.05 microg/ml) in human peripheral blood lymphocytes were assessed by the frequency of chromosome aberrations. Gamma rays (1.5 Gy) or bleomycin (1.5 microg/ml) were used as the challenge doses. In the experiments, blood samples from 5 healthy donors were investigated. It has been found that low doses of bleomycin and gamma rays induced a reciprocal adaptive response to high doses of gamma rays or bleomycin. Moreover, the results confirmed that the adaptive response did not correlate with the radiosensitivity of the peripheral blood lymphocytes.