Marta Molińska-Glura

PRAME expression in head and neck cancer correlates with markers of poor prognosis and might help in selecting candidates for retinoid chemoprevention in pre-malignant lesions

OBJECTIVES PRAME (Preferentially Expressed Antigen in Melanoma) is a tumor-associated antigen recognized by immunocytes, and it induces cytotoxic T cell-mediated responses in melanoma. PRAME expression in tumors interferes with retinoic acid receptor (RAR) signaling thus promoting tumor progression. Here, we study PRAME expression in head and neck squamous cell carcinoma (HNSCC) to determine its potential clinical significance. MATERIALS AND METHODS PRAME expression in HNSCC was evaluated by immunohistochemistry in tissue microarrays of primary tumors (n=53), metastatic lymph nodes (n=8) and normal oral mucosa (n=11). Biopsies of dysplastic oral lesions (n=12) were also examined. PRAME expression levels in tissues were correlated with markers of poor prognosis in HNSCC. PRAME mRNA in HNSCC cell lines and in normal immortalized human keratinocytes (HaCaT cell line) was measured by qRT-PCR, and the protein expression by flow cytometry and western blots. RESULTS PRAME was expressed in HNSCC cell lines and HNSCC lesions. PRAME expression in dysplastic mucosa was variable. No or only weak expression was found in normal cells or tissues. PRAME expression levels significantly correlated with the tumor grade, size, nodal involvement and the clinical status of HNSCC patients. CONCLUSIONS Elevated PRAME expression associates with clinicopathologic markers of poor outcome in HNSCC and might identify potential candidates with pre-cancerous lesions for chemoprevention with retinoids.

Test for screening olfactory function in children.

OBJECTIVE The research determining odors recognizable by children from Poland and Eastern Europe has not been widely described in the literature. The aim of the study was to determine the odors recognizable by Polish children which could be used in a screening olfactory test. METHODS The study was performed in Childrens Hospital in Warsaw. Ninety-one children aged from 2.9 years to 10 years (SD=5.6 years) were examined, 85 (93.4%) of which completed a full olfactory test. Children were separated into three age groups. The olfactory test consisted of 21 odors. RESULTS The analysis of the results of all childrens examinations showed statistically significant influence of age on the number of odors identified (p=0.0001; r=0.676). The olfactory test score enabled identification of 6 odors to be included in the screening test: bubble gum, lemon, cola, mint, toffee, fish. Correct identification of at least 4 out of them was accepted as a norm and was achieved by 96.5% of children. CONCLUSIONS Olfactory evaluation is possible for children as young as 3 years old. Childs age influences the number of odors recognized and the specific odors recognition depends also on the home place geographic location and eating habits. Eastern European children most often recognized the following odors: bubble gum, lemon, cola, mint, toffee and fish, as so these odors were considered for olfactory screening test. The 6 odors test has good ability to generalize performance to olfactory status, has normative data and good validity and reliability, is fast, easy and inexpensive to administer.

Physical activity and body composition, body physique, and quality of life in premenopausal breast cancer patients during endocrine therapy – a feasibility study

Abstract Endocrine therapy (ET) is a common method of treatment in breast cancer patients; however, its negative impact on body composition, body physique (physical body shape/measurements), and quality of life (QoL) remains controversial. Previous studies have shown physical exercise can have a positive effect on QoL in breast cancer patients, especially premenopausal subjects. Objective. In this feasibility study, we sought to assess the impact that physical exercise had on body composition and QoL in premenopausal breast cancer patients undergoing ET, and to determine the appropriateness of further testing of this intervention in this patient group. Material and methods. This study involved 41 premenopausal female breast cancer patients before and after six, 12, and 18 months of ET. Aerobic training began in the 6th month and resistance training was added in the 12th month. Body composition was evaluated using dual-energy x-ray absorptiometry (DXA) scans, body physique was evaluated using anthropometric measurement techniques, and QoL was evaluated using questionnaires from the European Organization for Research and Treatment of Cancer. Results. The initial period of ET with no exercise resulted in a reduction in fat-free body mass (FFBM), an increase in fat body mass (FBM), and a decline in QoL scores. Adding aerobic training resulted in a reduction of FBM and percentage of android fat, and improved QoL scores. The introduction of resistance training further reduced percentage of android and gynoid fat, increased FFBM, and further improved QoL scores. Conclusion. ET negatively impacts body composition, body physique, and QoL of premenopausal breast cancer patients. This feasibility study shows that physical activity may improve QoL and reduce adverse effects of ET on body composition and body physique, indicating appropriateness for further investigation on the use of exercise programs in premenopausal breast cancer patients to improve the outcomes of therapy.

The impact of an external breast prosthesis on the gait parameters of women after mastectomy.

Background: An integral part of the recovery process after mastectomy involves the consideration of restorative options, including external prosthesis use; however, only few studies regarding the influence of breast prostheses on functional status have been done. Objective: This study aimed to determine whether wearing an external breast prosthesis affects gait in women after a mastectomy. Methods: Spatiotemporal gait parameters were collected in 40 women, postmastectomy, aged 37 to 70 years, divided into age subgroups of 37 to 54 years and 55 to 70 years, and in 38 healthy controls, women aged 38 to 69 years. Gait parameters were assessed with and without the breast prosthesis, including walking velocity, cadence, step length, step time, and left-right step time asymmetry. Results: Significant differences were found in the gait parameters of the younger age group with and without a prosthesis. No significant differences were found in the women of the older group with and without the prosthesis. Conclusion: Gait parameters of the younger age group were closer to those of the healthy control group when they were wearing an external prosthesis, as compared with when they were not. This suggests a positive influence of breast prosthesis use on the functional status of women after mastectomy. Implications for Practice: Clinical practitioners should be aware of the study results suggesting a positive influence of breast prosthesis use on gait parameters after mastectomy surgery, which could improve the patient’s functional status after surgery; however, further research is still needed on factors affecting changes in gait with a larger study population.

Exercise tolerance in breast cancer patients during radiotherapy after aerobic training.

Aim of the study In spite of the introduction of dose constraints based on patient individual assessment techniques for radiation therapy (RT), some side effects from the heart and lungs are observed. Regular physical exercises improve efficiency, which was confirmed in clinical trials. The aim of this study was to evaluate endurance exercise tolerance and the impact of aerobic training (AT) on selected clinical parameters in breast cancer patients during RT. Material and methods This study involved 46 women with breast cancer who were irradiated using conformal technique (3DCRT) to a total dose of 50 Gray during a 5-week course of RT. In this period 25 patients (group A) simultaneously performed AT, and the rest of the patients, without rehabilitation (group B), undertook irregular physical activity on their own. The exercise tolerance was assessed through the 6-minute walk test (6MWT) using: oxygen saturation (SO2), heart rate (HR), blood pressure (BP), 6-minute walk distance (6MWD) and dyspnea scale. Results After AT in group A, a statistically significant (p < 0.05) decrease was observed in average diastolic BP before 6MWT and in HR parameters before and after 6MWT (p > 0.05), and 6MWD was increased (p < 0.05). In group B, after RT, an increase (p < 0.05) in HR was observed after the test as well as dyspnea. Oxygen saturation in both groups was not significantly changed. Conclusions The results of our study showed that regular AT after just 6 weeks caused an improvement in exercise tolerance parameters with a substantial decline in dyspnea in breast cancer patients receiving RT.

Impact of CYP2E1, GSTA1 and GSTP1 gene variants on serum alpha glutathione S-transferase level in patients undergoing anaesthesia

BackgroundThe serum glutathione S-transferase alpha (α-GST) concentration has been used as a marker of hepatic condition. After sevoflurane anaesthesia a mild impairment of hepatocellular integrity was observed. Genetic polymorphisms in CYP2E1, GSTA1 and GSTP1 genes, affecting enzymes activity, may possibly influence the hepatotoxic effect of sevoflurane. The aim of this study was to assess the influence of genetic polymorphism of CYP2E1, GSTA1 and GSTP1 genes on serum α-GST level in 86 unrelated patients representing ASA physical status I-II, undergoing laryngological surgery under general anaesthesia with sevoflurane.MethodsThe serum samples from three perioperative time points were analyzed using ELISA. Genetic variants were detected by pyrosequencing and sequencing. Finally, the statistical associations between serum α-GST concentration and analyzed alleles of CYP2E1, GSTP1 and GSTA1 genes were estimated.ResultsThe allele GSTA1*B (−567G, −69T, −52A) frequency was 0.43, whereas the alleles c.313G and c.341T of GSTP1 were identified with frequencies of 0.28 and 0.1 respectively. The -1053T allele of the CYP2E1 gene was observed with 0.01 frequency. We found serum α-GST concentrations in homozygous changes c.313A>G and c.341C>T of the GSTP1 gene significantly higher at the end of anaesthesia as compared with the levels at pre-anaesthetic and 24 h post-anaesthetic time points. Moreover, GSTA1 wild type genotype was associated with increased α-GST concentration at 24 h after the end of anaesthesia.ConclusionsGSTP1 gene polymorphism has an impact on the perioperative serum α-GST concentration in patients undergoing sevoflurane anaesthesia. A similar association, although not statistically significant exists between GSTA1 gene variants and perioperative serum α-GST level.

Longrange PCR-based next-generation sequencing in pharmacokinetics and pharmacodynamics study of propofol among patients under general anaesthesia

The individual response of patients to propofol results from the influence of genetic factors. However, the state of knowledge in this matter still remains insufficient. The aim of our study was to determine genetic predictors of variable pharmacokinetics and pharmacodynamics of propofol within selected 9 genes coding for propofol biotransformation enzymes, receptors and transporters. Our studies are the first extensive pharmaocgenetics research of propofol using high throughput sequencing technology. After the design and optimization of long range PCR-based next-generation sequencing experiment, we screened promoter and coding sequences of all genes analyzed among 87 Polish patients undergoing general anaesthesia with propofol. Initially we found that two variants, c.516 G > T in the CYP2B6 gene and c.2677 T > G in the ABCB1 gene, significantly correlate with propofol’s metabolic profile, however after Bonferroni correction the P-values were not statistically significant. Our results suggest, that variants within the CYP2B6 and ABCB1 genes correlate stronger with propofol’s metabolic profile compared to other 7 genes. CYP2B6 and ABCB1 variants can play a potentially important role in response to this anaesthetic and they are promising object for further studies.

Analysis of the relationship between coefficients of relatedness and molecular similarity of parental forms with respect to the heterosis effect in maize

SUMMARY Within the last twenty years studies have been conducted at many research centers with the aim of dividing breeding materials into heterotic groups based on molecular markers. Molecular techniques make it possible to study the genetic purity of inbred lines, determine their genetic variability and classify breeding materials for which no information is available on their origin. This study aims to investigate relationships between coefficients of relatedness (pedigree analysis) and molecular similarity estimated on the basis of AFLP and RAPD molecular markers, between parental forms of F1 maize hybrids. Determination of these relationships will make it possible to establish a hierarchy of importance for applied methods concerning selection of parental components for heterotic crossings based on the degree of relatedness and genetic similarity. As a result of the experiment it was shown that in the case of incomplete pedigree information, in the selection of parental components for crossings we may use information concerning molecular similarity determined using AFLP markers and the Jaccard index, which to the least degree differentiates matrices of AFLP and RAPD molecular similarity.

Attempt to adapt a statistical model for the heterosis effect in maize F1 hybrids depending on the genetic distance of parental forms

Attempt to adapt a statistical model for the heterosis effect in maize F1 hybrids depending on the genetic distance of parental forms During the recent years traditional tillage techniques and procedures have been successfully used in combination with the modern molecular technologies. This enables the researchers not only to employ more objective methods of parental material selection, but also shortens the time required to breed a new variant. Many researchers tried to surmise the heterosis effect by examining the genetic distance between two parental lines. The main objective of this work was to display the correlation between the heterosis effect among the F1 generation of maize and the genetic distance between the parental components. Furthermore, an attempt was made to predict the future heterosis effect using mathematical functions. Finding a proof of those correlations would make it possible to select the parental material, used to create a new variation, more effectively and thus to reduce the number of lines tested during the experiment. Hence it would reduce the time needed for the experiments and also significantly reduce the overall cost of the research project. The research displayed that the molecular markers AFLP and RAPD are useful for predicting the formula of a new corn hybrid. They can be also used to group lines according to their origin or parentage, including those having incomplete information about their parentage. For both markers: RAPD and AFLP, the functions that best describe the correlation between the heterosis effect and the genetic distance, were: a third degree polynomial y=a+bx+cx^2+dx^3 and a linear function y = a + bx.