Effects of Piptoporus betulinus Ethanolic Extract on the Proliferation and Viability of Melanoma Cells and Models of Their Cell Membranes.

Piptoporus betulinus is a fungus known for its medicinal properties. It possesses antimicrobial, anti-inflammatory, and anti-cancer activity. In this study, several tests were performed to evaluate the cytotoxic effect of the ethanolic extract of Piptoporus betulinus on two melanoma human cell lines, WM115 primary and A375 metastatic cell lines, as well as Hs27 human skin fibroblasts. The extract proved to affect cancer cells in a dose-dependent manner, and at the same time showed a low cytotoxicity towards the normal cells. The total phenolic content (TPC) was determined spectrophotometrically by the Folin-Ciocalteu method (F-C), and the potential antioxidant activity was measured by ferric-reducing antioxidant power (FRAP) assay. One of the active compounds in the extract is betulin. It was isolated and then its cytotoxic activity was compared to the results obtained from the Piptoporus betulinus extract. To further understand the mechanism of action of the extract's anticancer activity, tests on model cell membranes were conducted. A model membrane of a melanoma cell was designed and consisted of 1,2-dimyristoyl-sn-glycero-3-phosphocholine, disialoganglioside-GD1a and cholesterol: DMPC:GD1a:chol (5:2:3 mole ratio). Changes in a Langmuir monolayer were observed and described based on Π-Amol isotherm and compressibility modulus changes. LB lipid bilayers were deposited on a hydrophilic gold substrate and analyzed by IR and X-ray photoelectron spectroscopy. Our study provides new data on the effect of Piptoporus betulinus extract on melanoma cells and its impact on the model of melanoma plasma membranes.

Ferritin as a potential biomarker of efficacy of treatment of atrial fibrillation - preliminary report.

BACKGROUND: Complex mechanisms of responsible for originating and maintaining of atrial fibrillation (AF) are involved in pathophysiology of this arrhythmia. Inflammation substantially contribute to arrhythmic remodelling of atrial tissue.The aim of the present study is to assess an applicability of ferritin and high sensitive C-reactive protein (hs-CRP) as biomarkers of atrial fibrillation and their usefulness in evaluation of efficacy of cryoablation. MATERIALS AND METHODS: The study population consisted of 40 patients who underwent first AF cryoablation procedure. The whole follow-up time was for 6 months. The efficacy of cryoablation was defined as lack of episodes of AF longer than 30 s reported either in patient's medical documentation or present in standard or Holter ECG records. Concentrations of hs-CRP (latex method ) and ferritin (immunochemical method) were determined in standard way in hospital laboratory. RESULTS: The recurrence of atrial fibrillation during follow-up was detected in 7 of 40 patients (efficacy 82.5%). Basal concentrations of hs-CRP and ferritin were significantly higher in patients who underwent ablation during AF. Ablation resulted in an increase of either hs-CRP or ferritin concentrations. After seven days, both hs-CRP and ferritin concentrations returned to basal level. The trend toward the higher concentration of hs-CRP was observed in AF recurrence subgroup in 30th and the 90th day after the procedure. Ferritin concentrations were significantly higher in recurrence subgroup after 30 and 90 days. CONCLUSION: Our results suggest that the evaluation of ferritin serum level can be a potential tool for assessment of AF treatment efficacy.

Ultraconserved regions encoding ncRNAs are altered in human leukemias and carcinomas.

Noncoding RNA (ncRNA) transcripts are thought to be involved in human tumorigenesis. We report that a large fraction of genomic ultraconserved regions (UCRs) encode a particular set of ncRNAs whose expression is altered in human cancers. Genome-wide profiling revealed that UCRs have distinct signatures in human leukemias and carcinomas. UCRs are frequently located at fragile sites and genomic regions involved in cancers. We identified certain UCRs whose expression may be regulated by microRNAs abnormally expressed in human chronic lymphocytic leukemia, and we proved that the inhibition of an overexpressed UCR induces apoptosis in colon cancer cells. Our findings argue that ncRNAs and interaction between noncoding genes are involved in tumorigenesis to a greater extent than previously thought.

A differential microRNA profile distinguishes cholangiocarcinoma from pancreatic adenocarcinoma.

BACKGROUND: Cancers of the bile duct and the pancreas are virtually indistinguishable using conventional histopathological and clinical characteristics. We sought to use microRNA (miR) profiling to differentiate these two cancers. METHODS: RNA was harvested from the tumors of patients undergoing curative resection for cholangiocarcinoma or pancreatic adenocarcinoma and compared with adjacent normal bile duct or pancreas, respectively. There were 31 pairs of cholangiocarcinoma with matched tumor and adjacent bile duct and nine pairs of pancreatic cancer with matched tumor and adjacent uninvolved pancreas that had sufficient quantity of RNA that were included in the final analysis. Differential microRNA expression profiles were determined using the nCounter System from nanoString Technologies (Seattle, WA,USA). RESULTS: A total of 41 differentially expressed miRs were identified in cholangiocarcinoma (25 overexpressed, 16 underexpressed) and 52 differentially expressed miRs were found in pancreatic adenocarcinoma (30 overexpressed, 22 underexpressed) relative to adjacent normal tissue. Of these two profiles, 15 miRs were commonly dysregulated between tumor types. Also, eight miRs were similarly overexpressed or underexpressed in cholangiocarcinoma and pancreatic adenocarcinoma, whereas the other seven miRs had inverse expression levels. CONCLUSIONS: Cholangiocarcinoma has a distinct miR profile from pancreatic adenocarcinoma. Discrimination between these two tumor types may be possible with as few as seven miRs.

Estimation of the level of anthropogenic impact based on the determination of radionuclides and heavy metals in sediments taken from Rybnik reservoir, Poland.

The aim of the study was to estimate the degree of anthropogenic risk by evaluating the level of the contamination of sediments collected from the Rybnik reservoir. The results of the determination of radionuclides (137Cs, 40K, 228Th, 228Ra, 226Ra, 210Pb, 238U) and heavy metals (Zn, Cd, Pb, Cu, Cr, Ni) were presented. The Rybnik reservoir is located in a highly urbanised area, the Lower Silesian Voivodeship in Poland. Radionuclides (137Cs, 40K, 228Th, 228Ra, 226Ra, 210Pb, 238U) were measured using gamma spectrometry. The heavy metal (Zn, Cd, Pb, Cu, Ni and Cr) content was determined using an inductively coupled plasma optical emission spectrophotometer (ICP-OES). The classification of sediment pollution was made on the basis of geochemical and ecotoxicological indices. Radioactivity was varied with the highest for 40K (more than 200 Bq·kg-1). The concentrations for the remaining radionuclides were mostly below 20 Bq·kg-1. At the inlet zone (no. 9) an increase in radioactivity of each radioisotope was observed. The values of heavy metals from the lowest to the highest total amount in the sediments were as follows: Cd < Cr < Pb < Ni < Cu < Zn. The sediments of the reservoir are largely contaminated with Cu, but the sediments generally are contaminated to an average degree. Most pollutants accumulate in the inlet zone and near the dam wall. The content of artificial radionuclides, as well as the geochemical and ecological indicators used, can serve as an indicator of the level of anthropopressure in the vicinity of the Rybnik reservoir.

Hypoxia induces the overexpression of microRNA-21 in pancreatic cancer cells.

BACKGROUND: Pancreatic cancer cells exist in a hypoxic microenvironment containing numerous factors that impact tumor survival, proliferation, and metastasis. MicroRNAs (miRs) are differentially expressed in cancer but also altered by hypoxia. We hypothesized that hypoxia could induce expression of miR-21, an oncomir in pancreatic cancer cells. MATERIALS AND METHODS: We examined how hypoxia regulates miR-21 expression in pancreatic cancer cell lines (BxPC-3, AsPC-1) by stem-loop RT-PCR. Chromatin immunoprecipitation assays were used to study how hypoxia alters hypoxia-inducible factor (HIF)-1α binding to the hypoxia response element of miR-21. BxPC-3 and AsPC-1 cells were transfected with a constitutively stable HIF-1α subunit or vector control (pcDNA3.1) to determine the influence of miR-21 in normoxia. The effect of mature miR-21 sense and antisense oligonucleotides on proliferation and apoptosis in hypoxic and normoxic conditions was assessed via WST-1 assay and flow cytometry. RESULTS: MiR-21 levels increased in all cell lines grown in hypoxic conditions versus normoxia, whereas siRNA targeting HIF-1α reduced miR-21 expression. Hypoxic conditions resulted in direct binding of HIF-1α to the predicted binding site in miR-21. Transfection with a constitutively stable HIF-1α expression plasmid in normoxia resulted in upregulated miR-21, similar to that seen in hypoxia. Cells transfected with antisense constructs targeting miR-21 had reduced proliferation and increased apoptosis in normoxia, whereas miR-21 overexpression abrogated hypoxia-associated reductions in proliferation. CONCLUSIONS: MiR-21 is induced by hypoxia in pancreatic cancer cells via HIF-1α upregulation. MiR-21 overexpression allows cells to avoid apoptosis in a hypoxic microenvironment. Inhibition of miR-21 expression may increase cellular susceptibility to hypoxia in pancreatic cancer.

Concomitant dysregulation of microRNAs miR-151-3p and miR-126 correlates with improved survival in resected cholangiocarcinoma.

BACKGROUND: MicroRNAs (miRNAs) are small non-coding genes which become dysregulated in cancer and may predict survival. The role of miRNAs in outcomes in cholangiocarcinoma (CC) has not been reported. METHODS: RNA was extracted from 32 resected CCs along with adjacent uninvolved bile duct epithelium. A total of 43 miRNAs were quantified using NanoString™. Clinicopathologic characteristics and outcomes were captured and compared. Overall survival curves were created using the Kaplan-Meier method; factors, including miRNA expression, were compared by log-rank, chi-squared or Cox regression analyses. RESULTS: Absolute expression of each miRNA was compared with overall survival after excluding perioperative deaths (n= 3). One upregulated (miR-151-3p; P= 0.003) and one downregulated (miR-126; P= 0.023) miRNA in resected CC relative to adjacent normal bile duct epithelium correlated with survival on univariate analysis. Clinical factors and these miRNAs were compared. Dysregulated miR-151-3p and miR-126, respectively, were the only factors that correlated with improved overall survival [41.5 months vs. 12.3 months (P= 0.002) and 21.9 months vs. 15.1 months (P= 0.02), respectively]. In eight patients, both miRNAs were dysregulated. In the remainder, only one or neither showed dysregulation. Concomitant dysregulation correlated with the best overall survival (58.7 months vs. 15.1 months; P < 0.000; n= 8); clinicopathologic factors in these groups were otherwise similar. CONCLUSIONS: In resected CC, the concomitant dysregulation of both miR-151-3p and miR-126 was the factor related to the greatest improvement in overall survival. Further analysis of the targets of these miRNAs may yield potential therapeutic targets or prognostic biomarkers.

Perioperative Management of Dental Surgery Patients Chronically Taking Antithrombotic Medications.

The development of medicine is based not only on the introduction of new methods of treatment, but also on the use of increasingly effective drugs, including antithrombotic drugs. Drugs that inhibit the activity of platelets (antiplatelet and anti-aggregating drugs) and pharmaceuticals that inhibit the activity of plasma coagulation factors (anticoagulants) are used in antithrombotic therapy. In our daily practice we encounter patients who take chronic antiplatelet or anticoagulant drugs. However, more and more often we are dealing with patients who are treated with two antiplatelet drugs, an antiplatelet and an anticoagulant or even undergoing triple antithrombotic therapy. When preparing the patient for invasive craniofacial procedures, it should be assessed whether the temporary discontinuation of antithrombotic treatment due to the fear of excessive perioperative bleeding is justified and will not result in life-threatening thromboembolic complications. The authors discuss in detail the medications used in modern antithrombotic treatment and present a perioperative management procedure with a patient who takes l4 z of these medications chronically.

MiR-15a and miR-16-1 cluster functions in human leukemia.

MicroRNAs (miRNAs) are short noncoding RNAs regulating gene expression that play roles in human diseases, including cancer. Each miRNA is predicted to regulate hundreds of transcripts, but only few have experimental validation. In chronic lymphocytic leukemia (CLL), the most common adult human leukemia, miR-15a and miR-16-1 are lost or down-regulated in the majority of cases. After our previous work indicating a tumor suppressor function of miR-15a/16-1 by targeting the BCL2 oncogene, here, we produced a high-throughput profiling of genes modulated by miR-15a/16-1 in a leukemic cell line model (MEG-01) and in primary CLL samples. By combining experimental and bioinformatics data, we identified a miR-15a/16-1-gene signature in leukemic cells. Among the components of the miR-15a/16-1 signature, we observed a statistically significant enrichment in AU-rich elements (AREs). By examining the Gene Ontology (GO) database, a significant enrichment in cancer genes (such as MCL1, BCL2, ETS1, or JUN) that directly or indirectly affect apoptosis and cell cycle was found.

Association of a microRNA/TP53 feedback circuitry with pathogenesis and outcome of B-cell chronic lymphocytic leukemia.

CONTEXT: Chromosomal abnormalities (namely 13q, 17p, and 11q deletions) have prognostic implications and are recurrent in chronic lymphocytic leukemia (CLL), suggesting that they are involved in a common pathogenetic pathway; however, the molecular mechanism through which chromosomal abnormalities affect the pathogenesis and outcome of CLL is unknown. OBJECTIVE: To determine whether the microRNA miR-15a/miR-16-1 cluster (located at 13q), tumor protein p53 (TP53, located at 17p), and miR-34b/miR-34c cluster (located at 11q) are linked in a molecular pathway that explains the pathogenetic and prognostic implications (indolent vs aggressive form) of recurrent 13q, 17p, and 11q deletions in CLL. DESIGN, SETTING, AND PATIENTS: CLL Research Consortium institutions provided blood samples from untreated patients (n = 206) diagnosed with B-cell CLL between January 2000 and April 2008. All samples were evaluated for the occurrence of cytogenetic abnormalities as well as the expression levels of the miR-15a/miR-16-1 cluster, miR-34b/miR-34c cluster, TP53, and zeta-chain (TCR)-associated protein kinase 70 kDa (ZAP70), a surrogate prognostic marker of CLL. The functional relationship between these genes was studied using in vitro gain- and loss-of-function experiments in cell lines and primary samples and was validated in a separate cohort of primary CLL samples. MAIN OUTCOME MEASURES: Cytogenetic abnormalities; expression levels of the miR-15a/miR-16-1 cluster, miR-34 family, TP53 gene, downstream effectors cyclin-dependent kinase inhibitor 1A (p21, Cip1) (CDKN1A) and B-cell CLL/lymphoma 2 binding component 3 (BBC3), and ZAP70 gene; genetic interactions detected by chromatin immunoprecipitation. RESULTS: In CLLs with 13q deletions the miR-15a/miR-16-1 cluster directly targeted TP53 (mean luciferase activity for miR-15a vs scrambled control, 0.68 relative light units (RLU) [95% confidence interval {CI}, 0.63-0.73]; P = .02; mean for miR-16 vs scrambled control, 0.62 RLU [95% CI, 0.59-0.65]; P = .02) and its downstream effectors. In leukemic cell lines and primary CLL cells, TP53 stimulated the transcription of miR-15/miR-16-1 as well as miR-34b/miR-34c clusters, and the miR-34b/miR-34c cluster directly targeted the ZAP70 kinase (mean luciferase activity for miR-34a vs scrambled control, 0.33 RLU [95% CI, 0.30-0.36]; P = .02; mean for miR-34b vs scrambled control, 0.31 RLU [95% CI, 0.30-0.32]; P = .01; and mean for miR-34c vs scrambled control, 0.35 RLU [95% CI, 0.33-0.37]; P = .02). CONCLUSIONS: A microRNA/TP53 feedback circuitry is associated with CLL pathogenesis and outcome. This mechanism provides a novel pathogenetic model for the association of 13q deletions with the indolent form of CLL that involves microRNAs, TP53, and ZAP70.

Extreme Situation Experienced by Dental Students of the Medical University of Silesia Due to the SARS-CoV-2 Epidemic during the First Lockdown.

The pandemic declared in many countries in 2020 due to COVID-19 led to the freezing of economies and the introduction of distance learning in both schools and universities. This unusual situation has affected the mental state of citizens, which has the potential to lead to the development of post-traumatic stress and depression. This study aimed to assess the level of stress in dental students in the context of the outbreak of the SARS-CoV-2 virus pandemic. A survey on the PSS-10 scale was prepared to measure the level of perceived stress. The study included 164 dental students at the Faculty of Medical Sciences of the Medical University of Silesia in Katowice, Poland. The results showed the impact of COVID-19 on the stress of students, with 67.7% reporting high levels of stress. The study also revealed that stress was higher among older female students. This paper recommends that the university provide more intensive psychological care as psychological first aid strategies in epidemics or natural disasters and to consider telemedicine in order to deliver services due to the limitations of the pandemic.

Evaluation of the Most Stressful Dental Treatment Procedures of Conservative Dentistry among Polish Dental Students.

BACKGROUND: Dental schools are considered to be a very stressful environment; the stress levels of dental students are higher than those of the general population. The aim of this study was to assess the level of stress among dental students while performing specific dental procedures. METHODS: A survey was conducted among 257 participants. We used an original questionnaire, which consisted of 14 questions assigned to three categories: I-Diagnosis, II-Caries Treatment, and III-Endodontic Treatment. Each participant marked their perceived level of stress during the performed dental treatment procedures. The scale included values of 0-6, where 0 indicates no stress, while 6 indicates high stress. RESULTS: Third- (p=0.006) and fourth-year (p=0.009) women were characterized by a higher level of perceived stress during dental procedures related to caries treatment. Caries treatment procedures were the most stressful for 18.3% of third-year students, 4.3% of fourth-year students, and 3.2% of fifth-year students. Furthermore, 63.4% of third-year students, 47.3% of fourth-year students, and 17.2% of fifth-year students indicated that they felt a high level of stress when performing endodontic procedures. CONCLUSION: Third- and fourth-year female students are characterized by a higher level of stress during caries and endodontic treatment procedures. The most stressful treatments for participants were endodontic treatment procedures.

Non-codingRNA sequence variations in human chronic lymphocytic leukemia and colorectal cancer.

Cancer is a genetic disease in which the interplay between alterations in protein-coding genes and non-coding RNAs (ncRNAs) plays a fundamental role. In recent years, the full coding component of the human genome was sequenced in various cancers, whereas such attempts related to ncRNAs are still fragmentary. We screened genomic DNAs for sequence variations in 148 microRNAs (miRNAs) and ultraconserved regions (UCRs) loci in patients with chronic lymphocytic leukemia (CLL) or colorectal cancer (CRC) by Sanger technique and further tried to elucidate the functional consequences of some of these variations. We found sequence variations in miRNAs in both sporadic and familial CLL cases, mutations of UCRs in CLLs and CRCs and, in certain instances, detected functional effects of these variations. Furthermore, by integrating our data with previously published data on miRNA sequence variations, we have created a catalog of DNA sequence variations in miRNAs/ultraconserved genes in human cancers. These findings argue that ncRNAs are targeted by both germ line and somatic mutations as well as by single-nucleotide polymorphisms with functional significance for human tumorigenesis. Sequence variations in ncRNA loci are frequent and some have functional and biological significance. Such information can be exploited to further investigate on a genome-wide scale the frequency of genetic variations in ncRNAs and their functional meaning, as well as for the development of new diagnostic and prognostic markers for leukemias and carcinomas.

A microRNA signature of hypoxia.

Recent research has identified critical roles for microRNAs in a large number of cellular processes, including tumorigenic transformation. While significant progress has been made towards understanding the mechanisms of gene regulation by microRNAs, much less is known about factors affecting the expression of these noncoding transcripts. Here, we demonstrate for the first time a functional link between hypoxia, a well-documented tumor microenvironment factor, and microRNA expression. Microarray-based expression profiles revealed that a specific spectrum of microRNAs (including miR-23, -24, -26, -27, -103, -107, -181, -210, and -213) is induced in response to low oxygen, at least some via a hypoxia-inducible-factor-dependent mechanism. Select members of this group (miR-26, -107, and -210) decrease proapoptotic signaling in a hypoxic environment, suggesting an impact of these transcripts on tumor formation. Interestingly, the vast majority of hypoxia-induced microRNAs are also overexpressed in a variety of human tumors.

The Effect of 4'-hydroxy-3,4,5-trimetoxystilbene, the Metabolite of Resveratrol Analogue DMU-212, on Growth, Cell Cycle and Apoptosis in DLD-1 and LOVO Colon Cancer Cell Lines.

Resveratrol is a phytoalexin that naturally occurs in grapes, blueberries, cranberries, peanuts and many other plants. Although resveratrol inhibits carcinogenesis in all three stages, its clinical application is restricted due to poor pharmacokinetics. The methylated analogues of resveratrol have been found to have higher bioavailability and cytotoxic activity than that of the prototupe compound. Among the various methoxy derivatives of resveratrol, 3,4,5,4'-tetrametoxystilbene (DMU-212) is suggested to be one of the strongest activators of cytotoxicity and apoptosis. DMU-212 has been shown to exert anti-tumor activity in DLD-1 and LOVO colon cancer cells. Since colorectal cancer is the third most common cause of cancer-related deaths worldwide, the development of new anticancer agents is nowadays of high significance. The aim of the present study was to assess the anticancer activity of 4'-hydroxy-3,4,5-trimetoxystilbene (DMU-281), the metabolite of DMU-212, in DLD-1 and LOVO cell lines. We showed for the first time the cytotoxic activity of DMU-281 triggered via cell cycle arrest at G2/M phase and apoptosis induction accompanied by the activation of caspases-9, -8, -3/7. Furthermore, DMU-281 has been found to change the expression pattern of genes and proteins related to intrinsic as well as extrinsic apoptosis. Since the activation of these pathways of apoptosis is still the most desired strategy in anticancer research, DMU-281 seems to provide a promising approach to the treatment of colon cancer.

MicroRNAs in solid tumors.

MicroRNAs (miRNAs or miRs) are small, noncoding RNAs (approximately 20-22 nucleotides) that have critical functions in cell proliferation, apoptosis, and differentiation. These evolutionarily conserved RNA sequences are the result of a complex sequence of processing steps, which can regulate the expression of tens, and even hundreds, of genes. Their regulatory effect is based upon the degree of complementarity between the mature miRNA and the 3' untranslated region region of the target mRNA resulting in either complete degradation or translational inhibition of the target mRNA. In vertebrates they are often tissue specific in their expression patterns and dysregulated in malignancies. Thus, miRNA profiling has been used to create signatures for many solid malignancies. These profiles have been used to not only classify tumors, but also to help predict survival and outcome. Herein, we review the role of miRNAs in the development and progression of solid tumors.

The Reliability and Validity of the Telephone-Based and Online Polish eHealth Literacy Scale Based on Two Nationally Representative Samples.

Adequate ehealth literacy is one of the key instruments safeguarding people against unreliable health-related information obtained from the Internet. This paper presents an assessment of the reliability and the validity of a Polish version of the ehealth literacy scale (Pl-eHEALS). The assessment was carried out on the basis of two nationally representative samples of the Polish population. In the first survey of adults at least 50 years old, the technique of computer-assisted telephone interviewing (CATI) was applied. In the second survey of young adult women (18-35 years old), the technique of computer-assisted web interviewing (CAWI) was used. The reliability and the validity of the Pl-eHEALS was analyzed. There were no floor or ceiling effects revealed in either sample. The Cronbach's alpha coefficients were 0.90 and 0.88, and Guttman split-half coefficients were 0.89 and 0.81, respectively. Exploratory factors analysis revealed single factor models in both cases. The sum of squared loadings in the first survey was 6.090 and accounted for 58.72% of the variance. In the second survey, the sum was 5.927 and was responsible for 55.06% of the variance. Hypothesis testing showed that, for older adults, higher ehealth literacy was prevalent in the respondents who used the Internet more frequently. Among young adult women, higher readiness to use the Internet as a primary source of health-related information and to undertake specific internet health-related activities was associated with higher ehealth literacy. The analysis reported in this paper confirmed the reliability and the validity of the instrument. It should be stressed that, prior to this study, there was no validated Polish version of the eHEALS that could be used with Polish-speaking respondents.

A MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukemia.

BACKGROUND: MicroRNA expression profiles can be used to distinguish normal B cells from malignant B cells in patients with chronic lymphocytic leukemia (CLL). We investigated whether microRNA profiles are associated with known prognostic factors in CLL. METHODS: We evaluated the microRNA expression profiles of 94 samples of CLL cells for which the level of expression of 70-kD zeta-associated protein (ZAP-70), the mutational status of the rearranged immunoglobulin heavy-chain variable-region (IgV(H) ) gene, and the time from diagnosis to initial treatment were known. We also investigated the genomic sequence of 42 microRNA genes to identify abnormalities. RESULTS: A unique microRNA expression signature composed of 13 genes (of 190 analyzed) differentiated cases of CLL with low levels of ZAP-70 expression from those with high levels and cases with unmutated IgV(H) from those with mutated IgV(H) . The same microRNA signature was also associated with the presence or absence of disease progression. We also identified a germ-line mutation in the miR-16-1-miR-15a primary precursor, which caused low levels of microRNA expression in vitro and in vivo and was associated with deletion of the normal allele. Germ-line or somatic mutations were found in 5 of 42 sequenced microRNAs in 11 of 75 patients with CLL, but no such mutations were found in 160 subjects without cancer (P<0.001). CONCLUSIONS: A unique microRNA signature is associated with prognostic factors and disease progression in CLL. Mutations in microRNA transcripts are common and may have functional importance.

Alterations of the tumor suppressor gene ARLTS1 in ovarian cancer.

ARLTS1 is a tumor suppressor gene initially described as a low-penetrance cancer gene: a truncated Trp149Stop (MUT) polymorphism is associated with general familial cancer aggregation and, particularly, high-risk familial breast cancer. DNA hypermethylation has been identified as a mechanism of ARLTS1 expression down-regulation in lung carcinomas and B-cell chronic lymphocytic leukemia. We found that, in the majority of ovarian carcinomas (61.5%) and in a significant proportion of ovarian and breast cancer cell lines (45%), ARLTS1 is strongly down-regulated due to DNA methylation in its promoter region. After ARLTS1 restoration by adenoviral transduction, only the negative TOV-112 and the homozygously mutated (MUT) MCF7 cells, but not the OV-90 cells expressing a normal ARLTS1 product, underwent apoptosis and inhibition of cell growth. Furthermore, ARLTS1 reexpression significantly reduced the tumorigenic potential of TOV-112 in nude mice. On the contrary, the ARLTS1-MUT induced significantly lower levels of apoptosis in infected cells and reduced in vivo tumorigenesis only partially, supporting the hypothesis that Trp149Stop polymorphism is retained in the general population and predisposes to cancer because of a reduction, but not full loss, of normal ARLTS1 function.

[Complications after alcoholization of mental nerve]. / Powiklanie po alkoholizacji nerwu bródkowego.

Trigeminal neuralgia (TN) is a syndrome affecting usually one half of the face and consisting of severe pains within one or more branches of the nerve. One of the methods for conservative treatment is using anesthetic drugs in the form of perineural sensory branch blockades n. V. If these are found ineffective, alcoholic blockades are used in some cases although complications like necrosis, tissue fibrosis or risk of developing a neuroma may occur. The paper describes a case of complication after alcoholic blockade into left mental nerve, namely oral tissue necrosis.