High frequency of macrophages expressing elevated level of CD80, PD-Ls and TLR1 in nasal polyps of CRS patients

Identification of the association between tissue biomarkers, their surrogates in blood and clinical features, could provide new diagnostic tools and facilitate adequate choices of therapeutic interventions for selected patients suffering from CRS. The aim of present study was the assessment of macrophages in the polyp tissue and monocytes in the peripheral blood in the course of CRSwNP, and their functional immunophenotype. We analyzed 31 patients with CRSwNP. Nasal mucosa tissue was obtained via functional endoscopic sinus surgery (FESS). The control group included 10 patients with deviated nasal septum (DNS). Fluorochrome stained cells were proceed to acquisition using FACS Canto flow cytometer, and the results were analyzed using the software FACS Diva. In our study, we observed a significantly higher level of CD80, CD274, CD273 and TLR1 in nasal polyps compared to blood samples from patients with CRSwNP. This finding may suggest the importance of the PD-1 pathway as a therapeutic target in CRS and an important role for TLR1 in nasal polyp formation and maintenance. Our results may provide some insight into potential future targets of recurrent nasal polyp treatment and contribute to a better understanding of the inflammatory process in Chronic Rhinosinusitis.     

Fatigue Life of Austenitic Steel 304 Bolts Strengthened by Surface Treatment with Graphene Oxide Layer and Surface Shot Peening

This paper presents the results of investigations of the effect of graphene oxide and surface shot peening on the mechanical properties and fatigue life of bolts made of austenitic 304 steel. An innovative method for the uniform deposition of graphene oxide on screws is presented. The process involved activating the surface using plasma and then performing graphene oxide deposition using centrifugal force and vacuum drying. The screw specimens prepared in this way were subjected to a surface peening process. Comparative studies have shown that the combination of graphene oxide deposition and shot peening processes results in an increase in fatigue life of approximately 42 ÷ 275% (depending on the stress amplitude level) compared to the as-delivered samples. The results presented are promising and may provide a basis for further research on the application of graphene and its derivatives to increase fatigue life and improve the mechanical properties of machine components.     

Titanium–silicon ferrierites and their delaminated forms modified with copper as effective catalysts for low-temperature NH3-SCR

Titanium–silicon ferrierites with different Si/Ti ratios and their delaminated forms were modified with copper by ion-exchange. The obtained samples were characterized with respect to their chemical composition (ICP-OES), structure (XRD), texture (N₂ sorption), morphology (SEM), form and aggregation of titanium and copper species (UV-vis-DRS), reducibility of deposited copper species (H₂-TPR) and surface acidity (NH₃-TPD). The porous structure of the zeolitic samples strongly influenced the form and aggregation of deposited copper species. In the case of the three dimensional microporous structure of ferrierites (Ti-FER), copper was deposited mainly in the form of aggregated copper oxide species, in contrast to the open micro- and mesoporous structure of delaminated ferrierites (Ti-ITQ-6), where mainly copper in the form of monomeric cations was identified. It was shown that monomeric copper cations are more catalytically active in NO to NO₂ oxidation than aggregated copper oxide species and, therefore, for the low-temperature conversion of nitrogen oxides the fast SCR reaction pathway is more effective for delaminated ferrierites modified with copper (Cu-Ti-ITQ-6) than for microporous three dimensional ferrierite catalysts (Cu-Ti-FER).

Titanium–silicon ferrierites with different Si/Ti ratios and their delaminated forms were modified with copper by ion-exchange.     

The Associations between Metalloestrogens,GSTP1, and SLC11A2 Polymorphism and the Risk of Endometrial Cancer

Background: The incidence of endometrial cancer (EC) is still rising. Numerous risk factors including patient characteristics and molecular instability have been identified for EC. The presence of specific molecular markers allows specific diagnostic and prognostic approaches. Several single nucleotide polymorphisms (SNPs) have been identified to influence endometrial cancer risk. Metalloestrogens are metal ions which can mimic estrogen activity; however, their role in uterine pathologies remains unknown. This study aimed to investigate total blood trace elements levels and evaluate the distribution of selected genotypes in GSTP1 and SLC11A2 genes. Methods: This retrospective case-control analysis was carried out in peripheral blood samples of 110 women with endometrial cancer (EC; n = 21), uterine fibroma (n = 25), endometrial polyp (n = 48), and normal endometrium (n = 16). Analysis included measurement of metals and phosphor in serum, and of genetic polymorphisms in GST (rs1695) and SLC11A2 (rs224589) in DNA from white blood cells. Serum trace elements were measured using ICP-OES spectrometry. SNPs were identified using Taq Man real-time PCR genotyping assays. Results: The study confirmed higher age (OR 2.19, 95% CI 1.69–2.24), post-menopausal status (OR 1.89, 95% CI 1.36–1.94), and diabetes type 2 (OR 1.54; 95% CI 0.97–1.72) as independent risk factors for EC. We also found a high level of Cd (OR 1.49; 95% CI 1.31–1.63) and a low level of Co (OR 0.76; 95% CI 0.53–0.59) to be independent risk factors of EC. None of the tested polymorphisms of GSTP1 and SLC11A2 were associated with EC risk. However, high Cd (OR 1.21, 95% CI 1.15–1.29) and Ni (OR 1.07, 95% CI 1.05–1.18) serum levels were significantly associated with a SLC1A2 TG genotype, and high Cd levels with GSTP1 (OR 1.05, 95% CI 1.01–1.13).     

Molecular Effects of Iodine-Biofortified Lettuce in Human Gastrointestinal Cancer Cells

Considering the growing number of cancer cases around the world, natural products from the diet that exhibit potential antitumor properties are of interest. Our previous research demonstrated that fortification with iodine compounds is an effective way to improve the antioxidant potential of lettuce. The purpose of the present study was to evaluate the effect of iodine-biofortified lettuce on antitumor properties in human gastrointestinal cancer cell lines, gastric AGS and colon HT-29. Our results showed that extracts from iodine-biofortified lettuce reduce the viability and proliferation of gastric and colon cancer cells. The extracts mediated cell cycle arrest which was accompanied by inactivation of anti-apoptotic Bcl-2 and activation of caspases, as assessed by flow cytometry. However, extracts from lettuce fortified with organic forms of iodine acted more effectively than extracts from control and KIO₃-enriched plants. Using quantitative PCR, we detected the increase in pro-apoptotic genes BAD, BAX and BID in AGS cells whereas up-regulation of cell cycle progression inhibitor CDKN2A and downregulation of pro-proliferative MDM2 in HT-29 cells. Interestingly, lettuce extracts led to down-regulation of pro-survival AKT1 and protooncogenic MDM2, which was consistent for extracts of lettuce fortified with organic form of iodine, 5-ISA, in both cell lines. MDM2 downregulation in HT-29 colon cancer cells was associated with RB1 upregulation upon 5-ISA-fortified lettuce extracts, which provides a link to the epigenetic regulation of tumor suppressor genes by RB/MDM2 pathway. Indeed, SEMA3A tumor suppressor gene was hypomethylated and upregulated in HT-29 cells treated with 5-ISA-fortified lettuce. Control lettuce exerted similar effects on RB/MDM2 pathway and SEMA3A epigenetic activation in HT-29 cells. Our findings suggest that lettuce as well as lettuce fortified with organic form of iodine, 5-ISA, may exert epigenetic anti-cancer effects that can be cancer type-specific.     

The NOD2 3020insC Mutation in Women with Breast Cancer from the Bydgoszcz Region in Poland. First Results

The frameshift NOD2 gene mutation 3020insC is predominantly associated with Crohn's disease, but predisposes to many types of common cancers as well. We studied the frequency of this mutant NOD2 allele in 148 breast cancer women from the Bydgoszcz region in Poland. The NOD2 mutation was present in 8.8% of the patients. The mean age at breast cancer diagnosis of the mutation carriers was 43 years. We did not find any mutation in patients diagnosed with breast cancer after the age of 50 years. There was no association of the NOD2 mutation with a strong family history of breast cancer. On the contrary, the mutation frequency (11.4%) was two times higher in women from families with a single case of breast cancer and with aggregation of other common types of cancer, especially digestive tract cancers. Low risk of breast cancer in the mutation carriers seems to be confirmed by finding the 3020insC mutation in three healthy parents of probands aged 73, 74 and 83 years, from three separate families.     

Collagen deposition around polypropylene tapes implanted in the rectus fascia of female rats

OBJECTIVE: Implantation of the mesh induces a foreign-body reaction followed by the development of connective tissue that may alter tape property. The aim of our study was to evaluate the deposition of collagen in the vicinity of monofilament tension-free vaginal tape (TVT; Ethicon Inc., Johnson & Johnson) and multifilament intravaginal slingplasty (IVS; Tyco Healthcare) polypropylene tapes implanted in female rats. METHODS: The samples of the meshes (10 mg each) were implanted in the rectus fascia of 14 Wistar female rats and removed after 42 days. Collagen was extracted with 0.5 M acetic acid and subsequently with pepsin (1 mg/ml in 0.5 M acetic acid). Collagen concentration was measured using Sircol Collagen Assay (Biocolor Ltd.) and normalised for milligrams of tape weight. For histological examination, tape samples were stained with haematoxylin and eosin or with silver for type III collagen. RESULTS: The total amount of collagen extracted did not differ significantly between TVT and IVS samples. For both tapes, extraction with acetic acid yielded a higher amount of collagen (about 70%) than extraction with pepsin. On histological examination, less densely packed bundles of collagen fibres and a slightly more intense inflammatory reaction were observed with TVT compared with IVS mesh. CONCLUSION: The total amount of collagen deposited around the polypropylene mesh implanted in female rats was similar for TVT and IVS meshes, but differences were noted in the arrangement of the collagen fibres and the intensity of the inflammatory reaction.     

Macrocytosis during sunitinib treatment predicts progression-free survival in patients with metastatic renal cell carcinoma

Sunitinib, a multi-targeted receptor tyrosine kinase inhibitor, is a first-line treatment for metastatic renal cell carcinoma (mRCC) in patients in ‘low’ and ‘intermediate’ Memorial Sloan Kettering Cancer Center and Heng risk groups. Disruptions of hematopoiesis, such as anemia, neutropenia, and thrombocytopenia, are typically observed during sunitinib treatment. When it comes to RBC parameters, an increase in mean cell volume (MCV) tends to occur, meeting the criteria for macrocytosis in some patients (MCV > 100 fL). We examined changes in RBC parameters of 27 mRCC patients treated with sunitinib (initial dose of 50 mg/day, 6-week treatment: 4 weeks on, 2 weeks off) and correlated them with progression-free survival time (PFS). Patients who had macrocytosis after 3 treatment cycles had significantly longer PFS than those whose MCV stayed less than 100 fL (not reached vs. 11.2 months, p < 0.001). We also found a correlation between MCV values after the first and third treatment cycles and the risk of progression: HR of 0.9 (0.81–0.99) and 0.76 (0.65–0.90) per 1 fL increase in MCV, respectively. The mechanism of MCV elevation during sunitinib treatment has not yet been fully explained. One of the probable causes is sunitinib’s inhibitory influence on c-Kit kinase, as is the case with imatinib. For mRCC patients, this phenomenon could help predict PFS, but since our sample was small, further studies are essential.     

Limited significance of family history for presence of BRCA1 gene mutation in Polish breast and ovarian cancer cases

It is estimated that about 5–10% of ovarian and 2–5% of all breast cancer patients are carriers of a germline BRCA1 or BRCA2 gene mutation. Most families with detected BRCA1 or BRCA2 gene mutation are qualified for molecular testing on the basis of family history of breast or ovarian cancers. The purpose of our study was to establish the frequency of positive family history of cancer in a series of Polish consecutive breast and ovarian cancer patients in two groups, with and without the BRCA1 gene mutations. We analysed the prevalence of four of the most common BRCA1 mutations: 5382insC (c.5266dupC), 300T>G (p.181T>G), 185delAG (c.68_69delAG) and 3819del5 (c.3700_3704del5). The patient group consisted of 1,845 consecutive female breast and 363 ovarian cancer cases. 19 out of 37 (51%) of BRCA1-positive ovarian cancer patients and 21 out of 55 (39%) BRCA1-positive breast cancer had negative family history of breast and/or ovarian cancer among first- and second-degree relatives. In ovarian cancer patients, negative family history was more frequent in those with 300T>G BRCA1 gene mutation than in 5382insC carriers. This finding indicates the necessity of searching for 300T>G mutation in families with a single diagnosis of ovarian cancer in family. The high frequency of mutations detected in breast cancer patients lacking obvious family history shows that breast cancer patients should be qualified for genetic testing on the basis of wide clinical and pathological criteria.