Relationship between polymorphism rs2794521 in CRP gene and survival of depressive patients with chronic heart failure.

OBJECTIVE: Currently, there is a lack of studies combining the relationship between depression, chronic heart failure (CHF) and CRP polymorphisms (SNPs). The objective of the study was the investigation of the potential influence of rs2794521 in CRP on the survival and clinical profile of patients suffering from both depression and CHF. PATIENTS AND METHODS: 103 CHF individuals were studied to evaluate depression occurrence and to compare values of cardiac, laboratory and nutritional parameters depending on CRP genotypes. RESULTS: The higher frequency of CC genotype was found in depressive patients (p=0.021). Serum CRP concentration was significantly higher in depressed patients than in non-depressed ones (p=0.032). CC depressive individuals demonstrated greater frequency of NYHA grade III-IV (p<0.001) and higher level of circulating CRP (p=0.001) and TNF-α (p=0.042) compared with CT or TT carriers. CC individuals were more frequently classified as moderately or severely malnourished according to SGA (p=0.014). CC genotype was associated with a higher risk of early death during the 72 months of the follow-up (HR=4.01; p=0.006 for CC vs. CT vs. TT and HR=4.46; p<0.001 for CC vs. CT+TT). CONCLUSIONS: CC genotype of CRP more frequently occurs in depressive CHF patients, and it is associated with worse clinical outcomes and disease prognosis.

Effect of polymorphism rs1799964 in TNF-α gene on survival in depressive patients with chronic heart failure.

OBJECTIVE: To date, there are no literature reports combining the relationship between depression and chronic heart failure (CHF) in relations to selective nutritional, cardiac and laboratory parameters. The aim of this study was to correlate the rs1799964 genotypes in TNF-α with clinical outcomes of depressive CHF patients. PATIENTS AND METHODS: 94 CHF patients were enrolled to assess depression prevalence and to compare values of cardiac, laboratory and nutritional parameters between depressed and non-depressed patients with different rs1799964 genotypes. RESULTS: Depression was diagnosed in 66 individuals (70.2%). We noted significant reduction of EF% in CC genotype carriers compared to other patients (mean EF%: 36±11 CC vs. 44±14 CT and 46±7 TT; p=0.023) and worse outcomes in NYHA examination (p=0.033). We noticed a significant increase in serum CRP and TNF-α in CC patients (p=0.003 and p<0.001). Compared with T allele carriers, the CHF patients bearing CC genotype were more frequently diagnosed as cachectic (cachexia incidence for CC - 80% vs. 28% for CT and 38.7% for TT; p=0.017). CC genotype of rs1799964 was found as unfavorable factor affecting survival of depressive CHF patients (HR=8.87; p<0.001). CONCLUSIONS: The presence of the CC genotype in patients with depression and CHF can be considered an unfavorable prognostic factor related to the risk of shortening the life expectancy and deteriorating its quality, which is reflected in the severity of inflammation.

MiRNA and lung cancer radiosensitivity: a mini-review.

Radiotherapy (RTH) is still one of the leading treatment options for lung cancer patients. This treatment option is especially significant for patients with diagnosis of locally advanced or advanced tumor. To date, it is difficult to predict RTH outcomes basing only on patients' clinical features. Moreover, there are no established molecular markers, which could improve the prediction of RTH efficacy. Among the most promising markers which could serve as valuable biomarkers of RTH, miRNAs seem to be the most appropriate. According to literature reports, these molecules may be used for the prediction of RTH response, selection of patients who could benefit from RTH, as well as to estimate the risk of toxicity after irradiation. Moreover, thanks to the possibility of its testing in blood samples whenever it is required, miRNAs seem to be a much more attractive predictive marker of response to RTH than other molecular factors. In the present mini-review, we discuss recent findings of experimental studies (cell cultures analysis) and clinical studies concerning the relationship between miRNAs and sensitivity of lung tumors to RTH.

Status of hydration assessed by bioelectrical impedance analysis: a valuable predictive factor for radiation-induced oral mucositis in head and neck cancer patients.

BACKGROUND: Apart from surgery, the methods of treatment of HNC are radiotherapy (RTH) and/or chemotherapy (CRTH/CHT). One of the most frequent and serious complications of RTH is oral mucositis (OM). There is a strict correlation between the inflammation and the status of hydration. The aim of the study was to evaluate the changes in hydration, occurring in the course of RTH, measured by means of bioelectrical impedance analysis (BIA) and to analyze them in correlation with the intensification of OM in HNC patients. PATIENTS AND METHODS: Data from 49 HNC patients (stages I-IV) were analyzed. All of them were irradiated using IMRT technique with the doses of 50-70 Gy. Oral mucositis (OM) was evaluated according to RTOG/EORTC guidelines. BIA was performed using ImpediMed bioimpedance analysis SFB7 BioImp v1.55. RESULTS: In the fourth week of RTH, 4-5 days before the occurrence of severe OM, it was found that patients with OM grade 3 or higher compared to OM grade 2 or lower had significantly: lower ICW% values (respectively, 53.02% vs 50.72%; p = 0.0047), higher: ECW%: (47.95% vs 46.92%; p = 0.0020), TBW% (respectively, 56.34% vs 51.06%; p = 0.0455), ECW/ICW (respectively, 0.96 vs 0.86; p = 0.0007) and ECW/TBW (respectively, 0.49 vs 0.46, p = 0.0033). CONCLUSION: Our study indicates that HNC patients undergo changes in hydration in the course of RTH. We have also confirmed that the intensification of OM leads to ICW decrease and the increase of ECW, TBW as well as ECW/ICW and ECW/TBW values.

Three types of ion channels in the cell membrane of mouse fibroblasts.

Patch clamp recordings carried out in the inside-out configuration revealed activity of three kinds of channels: nonselective cation channels, small-conductance K(+) channels, and large-conductance anion channels. The nonselective cation channels did not distinguish between Na(+) and K(+). The unitary conductance of these channels reached 28 pS in a symmetrical concentration of 200 mM NaCl. A lower value of this parameter was recorded for the small-conductance K(+) channels and in a 50-fold gradient of K(+) (200 mM/4 mM) it reached 8 pS. The high selectivity of these channels to potassium was confirmed by the reversal potential (-97 mV), whose value was close to the equilibrium potential for potassium (-100 mV). One of the features of the largeconductance anion channels was high conductance amounting to 493 pS in a symmetrical concentration of 200 mM NaCl. The channels exhibited three subconductance levels. Moreover, an increase in the open probability of the channels at voltages close to zero was observed. The anion selectivity of the channels was low, because the channels were permeable to both Cl(-) and gluconate - a large anion. Research on the calcium dependence revealed that internal calcium activates nonselective cation channels and small-conductance K(+) channels, but not largeconductance anion channels.

Bioelectrical impedance phase angle as a prognostic indicator of survival in head-and-neck cancer.

BACKGROUND: Phase angle could be an alternative to subjective global assessment for the assessment of nutrition status in patients with head-and-neck cancer. METHODS: We prospectively evaluated a cohort of 75 stage iiib and iv head-and-neck patients treated at the Otolaryngology Department, Head and Neck Surgery, Medical University of Lublin, Poland. Bioelectrical impedance analysis was performed in all patients using an analyzer that operated at 50 kHz. The phase angle was calculated as reactance divided by resistance (Xc/R) and expressed in degrees. The Kaplan-Meier method was used to calculate survival. RESULTS: Median overall survival in the cohort was 32.0 months. At the time of analysis, 47 deaths had been recorded in the cohort (62.7%). The risk of shortened overall survival was significantly higher in patients whose phase angle was less than 4.733 degrees than in the remaining patients (19.6 months vs. 45 months, p = 0.0489; chi-square: 3.88; hazard ratio: 1.8856; 95% confidence interval: 1.0031 to 3.5446). CONCLUSIONS: Phase angle might be prognostic of survival in patients with advanced head-and-neck cancer. Further investigation in a larger population is required to confirm our results.

The relationship between polymorphisms of genes regulating DNA repair or cell division and the toxicity of platinum and vinorelbine chemotherapy in advanced NSCLC patients.

INTRODUCTION: Platinum-based chemotherapy and 3rd generation drugs is still the main treatment option for advanced non-small cell lung cancer (NSCLC) patients without activating EGFR mutations or ALK rearrangements. However, the side effects associated with cytostatics are well known. Changes in the genes (e.g. single nucleotide polymorphisms, SNPs) encoding proteins regulating DNA repair or cell division could potentially influence on both the susceptibility of cancer cells to chemotherapy, and the occurrence of toxicities. MATERIALS AND METHODS: In presented study, the relationship between the fourteen SNPs in nine DNA repair and cell division regulating genes: ERCC1, XPD, XPA, XPC, XRCC1, XPG, RRM1, BRCA1, STMN1 and the toxicity of first-line chemotherapy in NSCLC patients were investigated. SNPs were determined by SNaPshot PCR® in DNA isolated from peripheral blood of 55 NSCLC patients treated with platinum compound and vinorelbine. The toxicity of therapy was evaluated according to the Common Toxicity Criteria (CTC) Version 4.03. RESULTS: The odds ratio (OR) of severe haematological toxicity was significantly lower in carriers of the T allele of XRCC1 gene (1196A > G, OR = 0.22, 95 % CI: 0.06-0.82, p = 0.018) and higher in the carriers of the T allele (2704C > A) of XPC gene (OR: 7.50, 95 % CI: 0.89-63.17, p = 0.036) compared to the remaining patients. Risk of severe hepatotoxicity was significantly lower in carriers of the C allele of STMN1 (-2166T > C, OR = 0.09, 95 % CI: 0.01-1.12, p = 0.025) than in patients with T allele of this gene. In carriers of G allele (2251A > C, OR: 0.24, 95 % CI: 0.07-0.81, p = 0.017) and T (934G > A, OR: 0.26, 95 % CI: 0.07-0.90, p = 0.029) of XPD gene, risk of severe nephrotoxicity was significantly lower than in other patients. CONCLUSIONS: Selected SNPs of genes encoding DNA repair enzymes and cell division regulation proteins could be useful biomarkers for prediction of platinum and vinorelbine-based chemotherapy toxicity in patients with advanced NSCLC.

The relationship between RRM1 gene polymorphisms and effectiveness of gemcitabine-based first-line chemotherapy in advanced NSCLC patient.

PURPOSE: Chemotherapy with platinum compounds and gemcitabine is frequently used in first-line treatment of advanced non-small cell lung cancer (NSCLC) patients in which tyrosine kinase inhibitors (EGFR or ALK) cannot be administered. Unfortunately, less than half of the patients achieve the benefit from chemotherapy. Gemcitabine is an analog of deoxycytidine (pyrimidine antimetabolite) with antitumor activity. The excess of deoxycytidine synthesized by RRM1 enzyme activity may be a cause of competitive displacement of gemcitabine, which reduces the efficacy of this cytostatic. The aim of this study was to determine the association between single nucleotide polymorphisms (SNPs) of the RRM1 promoter (-37C>A, -524C>T) and the effectiveness of first-line chemotherapy based on platinum compounds and gemcitabine in NSCLC patients. PATIENTS AND METHODS: SNPs were determined by SNaPshot PCR(®) in DNA isolated from peripheral blood of 91 NSCLC patients. RESULTS: The median progression-free survival (PFS) was significantly longer in carriers of AA (-37C>A) as well as CC (-524C>T) genotype of RRM1 compared to patients with other genotypes (10.5 vs 3.5 months, p = 0.0437; HR = 2.17, 95 % CI 1.02-4.62 and 10.5 vs 3.5 months, p = 0.0343; HR = 2.12, 95 % CI 1.06-4.27). In addition, the CC genotype carriers (-37C>A) showed a significant increase in the risk of shortening overall survival (OS) in comparison to patients with AA or AC genotypes (9.5 vs 18 months, p = 0.0193; HR = 2.13, 95 % CI 1.13-4.03). CONCLUSIONS: Presence of rare AA (-37C>A) and CC (-524C>T) genotypes of the RRM1 may be favorable predictive factors for chemotherapy with platinum compounds and gemcitabine in NSCLC patients.

Retrospective analysis of second-line chemotherapy outcomes with paclitaxel or docetaxel in correlation with STMN1 polymorphism in advanced non-small cell lung cancer patients.

PURPOSE: Second-line chemotherapy of advanced non-small cell lung cancer (NSCLC) with docetaxel or pemetrexed allows to achieve objective response rate only in 5-10 % of patients. Recent studies have shown that single nucleotide polymorphisms (SNPs) in genes encoding proteins which regulate dynamics of microtubules may be considered as predictive factors of response to taxane-based chemotherapy. STMN1 gene encodes stathmin 1, which plays role in cell division by regulation of microtubules depolarisation, and this process may be associated with taxanes' effectiveness. MATERIALS AND METHODS: Using HRM-PCR technique, we evaluated the -2166C>T SNP of STMN1 gene in DNA from peripheral blood leucocytes of 54 advanced NSCLC patients treated in second-line monotherapy with docetaxel or paclitaxel. RESULTS: Patients with TT genotype of STMN1 gene demonstrated significantly longer progression-free survival (PFS) and the lower risk of early disease progression after second-line treatment compared to patients with other STMN1 genotypes (median PFS: 7 and 2 months; p = 0.0154; HR = 0.371; 95 % CI 0.184-0.743). Early disease progression during second-line chemotherapy was significantly more frequently observed in patients with CC genotype of STMN1 in contrast to patients with presence of T allele (median PFS: 2 and 4 months; p = 0.0385; HR = 1.776; 95 % CI 0.905-3.445). CONCLUSION: Only selected NSCLC patients could benefit from second-line chemotherapy. Therefore, investigations of novel predictive molecular factors for proper qualification of patients to second-line taxane-based chemotherapy are justified. Studied SNP of STMN1 gene may have potential predictive role in such therapy.

Tissue electrical properties in head and neck tumors before and after surgery: Preliminary observations.

Context: Bioelectrical impedance analysis (BIA) detects changes in tissue electrical properties and has been seen as a prognostic tool in several chronic conditions, including cancer. AIMS: The study was conducted to investigate whether there are any tissue electrical differences in patients with head and neck cancer (H and NC) before and after surgery treatment. Settings and Design: The observational study was performed at the Otolaryngology Department, Head and Neck Oncology. Materials and Methods : Tissue electrical properties were assessed in 31 patients with H and NC before and 2 weeks after surgery treatment. Direct bioimpedance measures [resistance, reactance, phase angle (PA)] were determined by BIA. Statistical Analysis Used: The Shapiro-Wilk test was used to assess the distribution conformity of examined parameters with a normal distribution; the Fisher (F) test was used to assess variance homogeneity. For group comparisons of metric data we used the Mann-Whitney U test. P value < 0.05 was considered as statistically significant. The statistical analysis for this study was performed using the computer software STATISTICA v. 8.0 (StatSoft). Results: PA at 50 kHz was found to be significantly (P = 0.000009) lower after surgery in patients with H and NC than before treatment (4.69° ±0.71 vs. 4.22 ± 0.83, respectively). Resistance was significantly (P = 0.0005) greater after surgery in patients with H and NC than before (596.24 ± 96.31 ohm vs 647.64 ± 276.11 ohm, respectively). Conclusions: There are tissue electrical differences before and after surgery in patients diagnosed with H and NC. Further observations would be useful to feedback in support therapy planning of individual patients.

Extracellular-to-body cell mass ratio and subjective global assessment in head-and-neck cancers.

BACKGROUND: The ratio of extracellular mass to body cell mass (ecm/bcm), determined by bioelectrical impedance analysis, has been found to be a potentially useful indicator of nutrition status. Subjective global assessment (sga) is a subjective method of evaluating nutrition status in head-and-neck cancer. The present study was conducted to investigate the association between ecm/bcm and sga in head-and-neck cancer. METHODS: Patients were classified as either well-nourished or malnourished by sga. Bioelectrical impedance analysis was conducted on a population of 75 patients with histologically confirmed head-and-neck cancer, and the ecm/bcm was calculated. Receiver operating characteristic curves were estimated using the nonparametric method to determine an optimal cut-off value of the ecm/bcm. RESULTS: Compared with malnourished patients, those who were well-nourished had a statistically significantly lower ecm/bcm (1.11 vs. 1.28, p = 0.005). An ecm/bcm cut-off of 1.194 was 76% sensitive and 63% specific in detecting malnutrition. CONCLUSIONS: The ecm/bcm can be an indicator that detects malnutrition in patients with head-and-neck cancer. Further observations are needed to validate the significance of the ecm/bcm and to monitor nutrition interventions.

Bioimpedance vector pattern in head and neck squamous cell carcinoma.

Direct bioimpedance measures (resistance, reactance, phase angle (PA)) determined by bioelectrical impedance analysis (BIA) detect changes in tissue electrical properties. The study was conducted to evaluate soft tissue hydration and mass through pattern analysis of vector plots as height, normalized resistance, and reactance measurements by bioelectric impedance vector analysis in patients with head and neck cancer. Whole-body measurements were made with ImpediMed bioimpedance analysis in 56 adult, white, male subjects 42 to 79 years old: 28 patients with head and neck squamous cell carcinoma (H&NC) and 28 healthy volunteers matched by sex, age and BMI as a control group. All patients were previously untreated and without active nutritional interventions. Mean vectors of H&NC group vs. the control group were characterized by an increased normalized resistance component with a reduced reactance component (separate 95% confidence limits, P<0.05), indicating a decreased ionic conduction (dehydration) with loss of dielectric mass (cell membranes and tissue interfaces) of soft tissue. Monitoring vector displacement trajectory toward the reference target vector position may represent useful feedback in support therapy planning of individual patients before surgery in patients with head and neck cancer in order to reduce post-operational complications.

Successful pregnancy in a chronically hemodialyzed patient with end-stage renal failure.

A 36 year-old female with chronic kidney failure due to hypertension and who was being treated with hemodialysis for eight months, was admitted to the hospital on the suspicion of being pregnant. Gynecological examination and ultrasound scan confirmed the pregnancy. Gestation was diagnosed in the 29(th) week after the patient felt fetal movements. Intensification of the dialysis treatment was started immediately after the diagnosis was made.

Simvastatin could prevent increase of the serum MMP-9/TIMP-1 ratio in acute ischaemic stroke.

MMP-9 plays an important role in the pathogenesis of AIS and predicts haemorrhagic transformation of the ischaemic focus. The aim of our study was to analyse both serum MMP-9 and its most specific endogenous inhibitor (TIMP-1) levels in AIS and to check whether HMG-CoA reductase inhibitor (simvastatin) affects the MMP-9/TIMP-1 ratio value. Fifty patients with AIS were randomly divided into two groups: Group I (N = 25) treated with 40 mg/day with simvastatin within 24 hours after the onset of stroke and Group II (N = 25) non-treated with statin. To evaluate MMP-9 and TIMP-1 serum levels, the ELISA method was used. The serum MMP-9 level was significantly elevated on the 7th day of stroke in both groups (from 668 to 862 ng/ml and 670 to 855 ng/ml, respectively, in Group I and II). The serum TIMP-1 level was also elevated on the 7th day of stroke in both groups but the results were not significant. The MMP-9/TIMP-1 ratio was elevated on the 7th day of stroke in both groups, but the result was significant only in the Group II (P < 0.01). These findings indicate that simvastatin given during 24 hours after the onset of stroke could have an influence on the MMP-9/TIMP-1 ratio during AIS.