I’m interested in translational research, i.e. studies that can be (almost) immediately transferred from the laboratory bench to the patient's bedside. In my research work, I focus on the role of microRNAs as biomarkers of early and late toxicity in the course of radiation therapy for the head and neck cancers as well as biology and clinical course of HPV-dependent cancers. In addition, I deal with issues related to the cellular response to fractionated total body irradiation.
Skills and Expertise
- Department of Biostatistics and Translational Medicine
- Łódź, Poland
- PhD Student
- Project "Predictive Biomarkers of Radiation Toxicity (PBRTox)" funded by the Foundation for Polish Science
- Department of Biostatistics and Translational Medicine
- Łódź, Poland
- Project Leader
- "MicroRNA profile in oropharyngeal cancer and its utility in radiotoxicity monitoring", Preludium 11 - financing provided by the National Science Center
Jul 2013 - Mar 2017
Medical University of Lodz
- Department of Pediatrics, Oncology, Hematology and Diabetology
- Łódź, Poland
- Project Leader
- “The relationship between NBN gene variability and the clinical course of acute lymphoblastic leukemia in children”, Diamond Grant - financing provided by Ministry of Science and Higher Education
Research Items (45)
Background: The role of isoprostanes in cerebral vasospasm (CVS) after aneurysmal subarachnoid haemorrhage (aSAH) has remained controversial. Recent studies have suggested that the level of isoprostanes in cerebral spinal fluid could play a role in aSAH patients outcomes. We have measured their concentration in urine as collection is simple and non-invasive. Due to their biological mechanism of action, it is essential to identify their role in aSAH patients. Methods: A prospective analysis of clinical data and urine samples of 20 patients with aSAH who underwent microsurgical clipping of the aneurysmal neck between May 2016 and January 2017. The role of isoprostanes as a CVS biomarker was analyzed with regard to patients’ clinical conditions. Outcome was assessed at discharge and during 1 month and 4 months’ follow-up using the Glasgow Outcome Scale and modified Rankin scale. Results: We noted that the concentration of urine F2-isoprostane was significantly greater in aSAH patients than in the healthy controls (p<0.001). Additionally, we observed that increased F2-isoprostane levels on day 3 after aSAH were associated with development of CVS (p=0.015) and worse performance after 1 and 4 months (p=0.042 and p=0.027, respectively). The prognostic value of urine F2-isoprostane on day 3 in terms of CVS was found to be high (AUC: 0.864, 95% CI: 0.691-1.000). Conclusions: Urine F2-IsopPs may be used as a new non-invasive prognostic biochemical marker in aSAH patients. F2-IsopPs levels in urine may have significant implications in the pathogenesis of CVS.
Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system (CNS). Four distinct disease courses are known, although approximately 90 % of patients are diagnosed with the relapsing-remitting form (RRMS). The name “multiple sclerosis” pertains to the underlying pathology: the presence of demyelinating plaques in the CNS, in particular in the periventricular region, corpus callosum, cervical spine, and the cerebellum. There are ongoing efforts to discover biomarkers that would allow for an unequivocal diagnosis, assess the activity of inflammatory and neurodegenerative processes, or warn of disease progression. At present, small noncoding RNA particles-microRNA (miRNA, miR) seem to be particularly noteworthy, as they take part in posttranscriptional regulation of expression of various genes. Changes in composition as well as function of miRNA found in body fluids of MS patients are subjects of research, in the hope they prove accurate markers of MS activity. This preliminary study aims to evaluate the expression of selected extracellular microRNA particles (miRNAlet-7a, miRNA-92a, miRNA-684a) in patients experiencing MS relapse and remission, with healthy volunteers serving as a control group and to evaluate the correlation between miRNA expression and selected clinical parameters of those patients. Thirty-seven patients suffering from MS formed two examined groups: 20 patients undergoing relapse and 17 in remission. Thirty healthy volunteers formed the control group. All patients who were subjects to peripheral blood sampling had been hospitalized in the Department of Neurology and Stroke. Four milliliters of venous whole blood had been collected into EDTA tubes. The basis for the selection of the three particular miRNA investigated in this study (miRNAlet-7a, miRNA-92a, miRNA-684a) was a preliminary bioinformatic analysis of data compiled from several medical databases, including Ovid MEDLINE®, Embase, Cochrane Database of Systematic Reviews (CDSR), miRWalk, and miRBase. The isolation of extracellular microRNA from plasma was carried out using miRNeasy Mini Kit (Qiagen) reagents. The reverse transcription was carried out with TaqMan® MicroRNA Reverse Transcription Kit (Applied Biosystems), as per manufacturers’ instructions. Standard microRNA TaqMan® tests (Applied Biosystems) were used for miRNA quantification. The qPCR were performed on a 7900 HT Fast Real-Time PCR System (Applied Biosystems) and analyzed using Sequence Detection System 2.3 software. In addition, all patients at the Department of Neurology and Stroke undergo a routine complete blood count with differential. The main objective of this study was to evaluate the expression of selected microRNA (has-miR-let-7a, miR-92a, and miR-648a) in the plasma of patients with MS during a relapse as well as in remission and attempt to correlate the acquired data with clinically relevant parameters of the disease. Finding such correlations may potentially lead to the use of miRNA as a biomarker of MS, which could help diagnose the disease and assess its severity and the efficacy of treatment. The difference in the expression of has-miR-let-7a in the remission group and the control group was statistically significant (p=0.002). Similarly, the expression of miRNA-648a in patients in remission was significantly different from the expression in the control group (p=0.02). Analysis of the correlation between the expression of miRNA-92a and the severity of the disease as measured by the EDSS scale in patients undergoing relapse showed significant negative linear correlation (r=−0.54, p=0.01). Higher miR-648a expression correlated with more frequent flare-ups in the joint group of patients in remission and relapse (p=0.03). This study is one of the few that demonstrate significantly changed expression of selected extracellular miRNA in plasma of MS patients and correlate those findings with clinical parameters. These observations may suggest that some miRNA subsets may be potential biomarkers for MS activity.
- Apr 2019
Purpose To evaluate the prognostic potential of lipopolysaccharide-binding protein (LBP) levels after breast cancer radiotherapy (RT) for incipient cardiac dysfunction. Methods and Materials In this single-centered study, we prospectively enrolled female patients treated for left breast cancer. Healthy age- and sex-matched participants were recruited as controls. LBP levels, cardiac troponin T (cTnT), N-terminal propeptide of the brain natriuretic peptide (pro-ntBNP), fatty acid binding protein (FABP) and C-reactive protein (CRP) were assessed at three timepoints – before RT, after the last RT fraction and one month after the last fraction. Echocardiographic evaluation was done 3-3.75 years after RT. Results We recruited 51 patients and 78 controls. Baseline LBP concentrations in the study group were significantly higher than in controls at baseline (p<0.001), 24 hours and 1 month after RT (p=0.003 and p<0.001, respectively). Other biomarkers (cTnT, pro-ntBNP, FABP and CRP) did not differ in any of the timepoints. Post-treatment LBP concentrations were significantly and positively correlated with heart and lung-associated dose-volume histogram (DVH) variables. Post-treatment and follow-up LBP levels correlated positively with the E/E’ echocardiographic index reflective of the diastolic function. After adjustment for left anterior descending artery mean dose (LADmean), left ventricle mean dose (LVmean), mean heart dose (MHD) and type of surgery, LBP remained significantly correlated with E/E’ when measured 24 hours after RT (beta=0.41, p=0.032) and one month after RT (beta=0.43, p=0.028). Conclusions Serum LBP concentrations correlate with diastolic function evaluated 3 years after the completion of RT, making LBP a potentially useful prognostic parameter.
The germline variant at rs3824662 in GATA3 is a risk locus for Philadelphia‐like acute lymphoblastic leukemia (Ph‐like ALL), the biological subtype of B‐cell precursor (BCP)‐ALL defined by a distinct gene expression profile and the presence of specific somatic aberrations including rearrangements of CRLF2. In this study, we investigated whether rs3824662 in GATA3 associates with CRLF2 expression in leukemic cells and predicts prognosis in pediatric BCP‐ALL patients treated according to the ALL Intercontinental Berlin‐Frankfurt‐Münster (IC BFM) 2009 (n=645) and the ALL IC BFM 2002 (n=216) protocols. High expression of CRLF2 was observed at both protein and mRNA levels (4‐fold higher in AA than in CA+CC) among GATA3 AA variant carriers, independent of the presence of P2RY8‐CRLF2 fusion. Additionally, the AA variant at rs3824662 was a significant factor affecting minimal residual disease (MRD) level at the end of induction phase and overall survival (OS) regardless of the risk group and the protocol. The germline variant at rs3824662 in GATA3 is a prognostic factor which associates with CRLF2 expression in leukemic cells supporting the hypothesis that GATA3 may have a regulatory effect on the CRLF2 pathway in pediatric BCP‐ALL. This article is protected by copyright. All rights reserved.
Purpose/Objective(s): Deep-inspiration breath-hold (DIBH) is a widely used and highly efficient technique of adjuvant left breast radiotherapy (RT), associated with lower radiation exposure to the left anterior descending artery (LAD). This technique involves patient training and coaching and high level of compliance is required. Hence, DIBH cannot be performed in some patients with left-sided breast cancer and free-breathing (FB) tangential RT is usually used. Volumetric modulated arc therapy (VMAT) can achieve highly conformal dose distributions and reduces treatment time. The aim of our study was to evaluate whether the patients who are ineligible for DIBH will benefit from free-breathing volumetric modulated arc therapy (FB-VMAT). Materials/Methods: Twenty patients with left-sided breast cancer underwent computed tomography simulation and images were obtained in both FB and DIBH. Ten patients were ineligible for DIBH and in this group FB-VMAT plans were generated. In FB and DIBH plans 42.72 Gy in 16 fractions was prescribed to breast tissue with 10.0 Gy boost in 4 fractions to the tumor bed. In FB-VMAT group simultaneous integrated boost planning was performed and 54.0 Gy in 20 fractions was prescribed. Treatment plans (DIBH, FB and FB-VMAT) were compared using various parameters, including mean heart dose, mean and maximal LAD dose, mean ipsilateral lung dose, percentage of ipsilateral lung receiving 20 Gy (Lung V20), mean contralateral lung dose and mean contralateral breast dose. Statistical analysis was performed using one-way ANOVA and with post-hoc Tukey test. Results: Mean heart dose was significantly lower in DIBH plans (1.96 Gy, p<0.001) compared to FB (7.05 Gy) and FB-VMAT plans (6.99 Gy). Mean LAD doses for DIBH, FB and FB-VMAT plans were 10.61 Gy, 35.71 Gy and 20.15 Gy (p < 0.001) and maximal LAD doses were 33.64 Gy, 45.59 Gy and 35.20 Gy (p<0.001), respectively. Mean ipsilateral lung dose was significantly higher in FB-VMAT plans (11.32 Gy, p=0.006) compared to FB (7.72 Gy) and DIBH (8.49 Gy) plans while no significant difference was noted for Lung V20 (15.74 Gy, 15.42 Gy and 14.91 Gy, respectively; p=0.956). Mean contralateral lung dose was significantly higher in FB-VMAT plans (3.31 Gy, p<0.001) compared to FB (0.31 Gy) and DIBH (0.28 Gy) plans. Mean contralateral breast dose was also significantly higher in FB-VMAT plans (2.65 Gy, p<0.001) compared to FB (0.47 Gy) and DIBH (0.43 Gy) plans. Conclusion: Compared to the FB plans, the FB-VMAT plans allowed significant dose sparing in LAD in terms of both mean and maximal dose. However, mean heart dose reduction was achieved only in DIBH plans. In addition, VMAT-FB plans resulted in significantly higher mean doses for both ipsi- and contralateral lung and contralateral breast which may be attributed to a higher whole-body exposure to leakage radiation described in this technique. This trade-off should be considered before implementation of VMAT-FB treatment planning in patients ineligible for DIBH.
- Aug 2018
Background: Papillary tumors of the pineal region (PTPRs) are malignant WHO grade II/III tumors, however they may perfectly mimic benign tumors, e.g. pineocytomas (WHO grade I). Case description: We present a case of a 28-year-old male with a 35mm tumor of the pineal region. Considering the typical radiological and pathological presentation, the tumor was firstly diagnosed as pineocytoma. However, despite first total resection the tumor recurred after 7 years. The recurrent neoplasm was composed mainly of papillary structures with low-grade atypical cells positive for CKAE1/AE3 and CK18. This lead to the final diagnosis of PTPR. The patient underwent adjuvant radiotherapy, which vastly improved his neurological condition and resulted in significant tumor regression. Conclusions: This case exemplifies that PTPRs can perfectly mimic pineocytomas and simple staining for cytokeratins may warrant the correct diagnosis and better treatment allocation.
- Jun 2018
Due to tremendous technological advances, radiation oncologists are now capable of personalized treatment plans and deliver the dose in a highly precise manner. However, a crucial challenge is how to escalate radiation doses to cancer cells while reducing damage to surrounding healthy tissues. This determines the probability of achieving therapeutic success whilst safeguarding patients from complications. The current dose constraints rely on observational data. Therefore, incidental toxicity observed in a minority of patients limits the admissible dose thresholds for the whole population, theoretically narrowing down the curative potential of radiotherapy. Future tools for measurements of individual's radiosensitivity before and during treatment would allow proper treatment personalization. Variation in tissue tolerance is at least partially genetically-determined and recent progress in the field of molecular biology raises the possibility that novel assays will allow to predict the response to ionizing radiation. Recently, microRNAs have garnered interest as stable biomarkers of tumor radiation response and normal-tissue toxicity. Preclinical studies in mice and non-human primates have shown that serum circulating microRNAs can be used to accurately distinguish pre- and post-irradiation states and predict the biological impact of high-dose irradiation. First reports from human studies are also encouraging, however biology-driven precision radiation oncology, which tailors treatment to individual patient's needs, still remains to be translated into clinical studies. In this review, we summarize current knowledge about the potential of serum microRNAs as biodosimeters and biomarkers for radiation injury to lung and hematopoietic cells.
Purpose/Objective: One of the most frequently reported side effect of radiotherapy in the head and neck region is xerostomia. Higher than grade 2 acute xerostomia is noted in about 75% patients treated for head and neck cancer. There is an increasing interest in the prevention of radiation-induced xerostomia because reduced salivary output may result in problems with mastication, digestion, swallowing and increase the risk of oral infections. Hence, the aim of this study was to create an efficient serum miRNA-based test predictive for xerostomia in patients treated for oropharyngeal squamous cell carcinoma (OPSCC). Material/Methods: Our study is designed as a prospective cohort study which enrolled OPSCC patients treated with IMRT (total dose of 70Gy or equivalent) from June 2016. Until now, we have recruited 44 OPSCC patients and 31 patients (70%) developed acute grade≥3 xerostomia. We randomly selected a group of 10 patients with grade≥3 xerostomia and matched a comparative group of 10 patients without severe xerostomia. We performed microRNA profiling of serum samples collected within 24 hours after the last fraction of RT using qPCR arrays (miRCURY LNA, Human panels I & II, Exiqon, Copenhagen, Denmark). Expression data were normalized toward the average expression of microRNAs detectable in all samples. Acute side effects were prospectively assessed using EORTC QLQ-C30 and EORTC H&N-35 questionnaires. The primary endpoint was moderate-to-severe (grade ≥3) patient-rated xerostomia reported 3 months after the end of treatment. The choice of candidate microRNAs for the classifier was based on differential expression, false discovery rate was controlled using Benjamini-Hochberg method. The classifier for patient-rated xerostomia was created using 5-fold cross-validated logistic regression model built after significance-based feature selection. The study was funded by the National Science Centre within the framework of Preludium 11 project (2016/21/N/NZ5/01938). Results: Ten patients (50%) suffered from moderate-to-severe xerostomia 3 months after treatment. Out of 540 miRNAs measured in at least one sample, 49 were detected in all 20 samples. After correction for multiple hypothesis testing, two microRNAs: miR-425-5p and miR-26b-5p, were found to be differentially expressed as depicted on Figure. The logistic regression model based on miR-425-5p and miR-26b-5p showed nearly perfect separation of the groups with AUC 0.98 (95%CI: 0.93–1.00) and maintained its performance in 5-fold cross validation (AUC=0.96, 95%CI: 0.88–1.00). Hosmer-Lemeshow’s test showed a very good fit of the model (p=1.00). Conclusion: A classification model based on serum expression of miR-425-5p and miR-26b-5p allowed nearly perfect prediction of xerostomia 3 months after treatment, however further studies with an external validation set are needed to confirm the model’s accuracy in a larger population.
Introduction: Posterior circulation aneurysms account for approximately 30% of all intracranial aneurysms, and their rupture often causes aneurysmal subarachnoid hemorrhage (aSAH). Because surgical treatment of posterior circulation aneurysms is difficult, endovascular treatment is commonly indicated. However, simple coil embolization is associated with a high rate of recanalization. Our goal was to investigate morphometric aneurysmal features assessed on pre-embolization computed tomography angiography (CTA) as predictors of recanalization in patients with posterior circulation aneurysms. Material and methods: We retrospectively analyzed data of 24 patients who underwent coil embolization due to rupture of saccular posterior circulation aneurysms. The morphometric features of aneurysms were measured based on pre-embolization 3D-CTA-aneurysm models, and aneurysmal size and volume were measured on digital subtraction angiography (DSA) images. The effectiveness of initial endovascular treatment was determined visually with the modified Raymond Roy classification directly after embolization and on follow-up DSAs. Recanalization was diagnosed when, compared to the primary embolization aneurysm appearance, compaction and filling of the aneurysm occurred. Statistical analysis was performed with Statistica 13.1 software. Results: Higher maximal aneurysm height perpendicular to the aneurysmal neck was associated with a greater aneurysm recanalization risk (12.12±5.13mm vs. 7.41±3.97mm, p=0.039), and this relationship remained significant after adjustment for patient’s age, sex and aneurysm localization (OR=1.26, 95%CI: 1.01-1.60, p=0.047). Maximal aneurysm height perpendicular to the aneurysmal neck distinguished well between recanalized and non-recanalized aneurysms (AUC=0.755, 95%CI: 0.521- 0.989, p=0.033). Conclusions: Predictors of aneurysm recanalization can help choose best endovascular treatment strategies, which could reduce complication rates.
Purpose/Objective(s): Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor in adults and its prognosis, despite the best efforts, remains poor. Taking into consideration the paucity of reliable clinical predictors in patients with GBM and because of the large molecular heterogeneity of cases, increasing importance is given to molecular subclassifications of GBM. Limited findings in gliomas biology (e.g. MGMT methylation or 1p/19q codeletion) now allow the identification of a group of patients with a better prognosis. The aim of our study was to analyze the influence of selected clinical factors and molecular prognosis in patients with GBM. Materials/Methods: The study group consisted of 244 patients treated for GBM in the years 2007-2015. This cohort was retrospectively analysed in order to evaluate the influence of selected clinical and molecular factors on patients overall survival (OS). The assessment of molecular abnormalities was done on DNA was extracted from formalin-fixed and paraffinembedded tissue with utilization of multiplex ligation-dependent probe amplification method and Sanger sequencing. Results: The study group consisted of 103 women (42.21%) and 141 men (57.79%). The average age of the patients was 55.3 10.7 years. Higher preoperative Karnofsky Performance Scale scores (HR=0.89, 95% CI: 0.87-0.91; p <0.001) and concurrent radiochemotherapy with temozolomide (HR=0.38, 95%CI: 0.25-0.61; p<0.001) were associated with a better prognosis for patients. Higher age at diagnosis was found to be significantly associated with worse prognosis - HR=1.06 (95% CI: 1.04-1.07); p <0.001. In terms of molecular markers, we have shown that the incidence of chromosome 7 polysomy significantly worsened prognosis (HR=2.37, 95% CI: 1.20-5.84; p=0.022) while EGFRvIII expression was associated with a better prognosis (HR =0.71, 95%CI: 0.54-0.97; p=0.041). Conclusion: Despite many years of research, GBM remains the most lethal tumor of the central nervous system with very poor natural history. The results of our study indicate that the modern classification of gliomas should take into account both clinical and molecular factors thereby allowing more precise diagnosis and tailored therapy in this group of patients.
Purpose/Objective(s) Xerostomia is a common complication in patients treated for head and neck cancers (HNC). Highly conformal radiotherapy (RT) techniques, such as intensity modulated radiotherapy (IMRT), result in better normal tissue sparing in comparison to 3-dimensional conformal radiotherapy. We investigated salivary function using quantitative scintigraphy and aimed to identify associations between dosimetric parameters of the parotid glands and quality of life (QoL) for HNC patients receiving IMRT. Materials/Methods Thirty patients treated for HNC were prospectively recruited. Salivary excretion function (SEF) was measured by 99mTc pertechnetate scintigraphy prior to RT and then 1 and 12 months after its completion. The recovery of parotid gland excretion function was expressed as the ratio of post- and pre-treatment SEF. Patient-reported QoL was evaluated by the EORTC QLQ-C30 and H&N35 questionnaires. Results The mean SEF before RT was 49.2±14.8%. In the univariate analysis we found that older age (r=-0.29, p=0.049) and localization of tumour in oral cavity or oropharynx (comparing to larynx/hypopharynx, p=0.030) affected recovery of salivary flow 12 months after RT. Mean parotid dose was significantly correlated with recovery of salivary flow 12 months after RT (r=-0.46, p=0.001). In the multivariate analysis all aforementioned factors were found to be significantly associated with salivary flow 12 months after RT - age (β=-0.39, p=0.002), tumour localized in oral cavity or oropharynx (β =-0.36, p=0.004), mean parotid dose (β=-0.44, p<0.001). Self-reported grade ≥3 xerostomia was more often in patients with tumour localized in oral cavity or oropharynx (p=0.027). It was also more common in patients who received higher mean dose for both parotids and in patients with worse recovery of salivary flow 12 months after RT. However these results were not statistically significant (p=0.104 and p=0.089, respectively). Conclusion The results of scintigraphic evaluation of salivary function are strongly correlated with the mean parotid dose. However, this objective method is only partially associated with patients’ self-reported outcomes. The possible reason for that phenomenon is the fact that xerostomia is highly subjective and several factors, not just simply salivary flow, may be involved in its perception. This may be particularly important in older patients who were found to have the worst recovery of salivary flow.
Objective: We present a case of a patient with pineal region tumour with typical features of pineocytoma, which recurred after 7 years as a papillary tumour of the pineal region (PPTR). Method: The analysis of clinical setting along with radiological and histopathological image lead us to the final diagnosis. Results: In 2007, a 28 years-old male was diagnosed with a welldelineated 35 mm tumour in the pineal region with a strong, homogenous contrast enhancement both in CT&MRI scans. The tumour histopathologically consisted of solid and highly-cellular areas with small, uniform cells that formed typical rosettes. Atypia, mitoses and necrosis were absent. The tumour was positive for Synaptophysin, NSE, negative for GFAP. Ki67 index was 1 %. Considering the typical presentation, the tumour was diagnosed as WHO grade I pineocytoma. After 7 years, the neoplasm recurred and was composed mainly of papillary structures with cells with low-grade atypia. Rosettes, mitoses and necrosis were absent. The recurrent tumour was only focally positive for Synaptophysin, negative for GFAP, but it was positive for CKAE1/AE3 and CK18 which lead to the final diagnosis of a PPTR. Conclusion: Our case shows that PPTRs can perfectly mimic pineocytomas. In such cases, staining for cytokeratins may lead to the correct primary diagnosis.
PurposeThe purpose of this study was to investigate the association between body mass index (BMI) and the results of SCARF osteotomy of the first metatarsal for hallux valgus (HV) correction, as the literature on this is scant. Methods This prospective study was carried out between 2011 and 2015. One hundred and thirty-three patients diagnosed with moderate to severe HV underwent a SCARF corrective osteotomy. We divided the patients into two groups according to their BMI: normal and overweight. Postoperative follow-up was two years. All patients were examined twice by two medical doctors simultaneously: pre-operatively and post-operatively at two years’ follow-up. Data collected included biometrical records, X-rays [HV angle (HVA), intermetatarsal angle (IMA), American Orthopaedic Foot and Ankle Society Hallux Metatarsophalangeal Index (AOFAS-HMI) and visual analogue scale (VAS) for pain and satisfaction]. ResultsThere was a significant difference between patient age (p = 0.001), age at onset (p < 0.001) and AOFAS-HMI (p = 0.035) at follow-up. Other parameters were similar in both groups. Conclusion Regardless of BMI, the radiological outcome was comparable. Despite a significant difference in AOFAS-HMI results, pain and satisfaction level were similar. The authors agreed that high BMI has protective role in the prevalence of HV.
- Feb 2017
The aim of this study was to evaluate the possible role in and contribution of antioxidant enzymes to bladder cancer (BC) etiology and recurrence after transurethral resection (TUR). We enrolled 40 patients with BC who underwent TUR and 100 sex- and age-matched healthy controls. The analysis was performed at diagnosis and recurrence, taking into account the time of recurrence. Gene expression of catalase (CAT), glutathione peroxidase 1 (GPX1) and manganese superoxide dismutase (SOD2) was determined in peripheral blood leukocytes. The activity of glutathione peroxidase 3 (GPX3) was examined in plasma, and GPX1 and copper-zinc containing superoxide dismutase 1 (SOD1) in erythrocytes. SOD2 and GPX1 expression and GPX1 and SOD1 activity were significantly higher in patients at diagnosis of BC in comparison to controls. In patients who had recurrence earlier than 1 year from TUR, CAT and SOD2 expression was lower (at diagnosis p=0.024 and p=0.434, at recurrence p=0.022 and p=0.010), while the GPX1 and GPX3 activity was higher (at diagnosis p=0.242 and p=0.394, at recurrence p=0.019 and p=0.025) compared to patients with recurrence after 1 year from TUR. This study revealed that the gene expression and activity of the antioxidant enzymes are elevated in blood of patients with BC, although a low expression of CAT might contribute to the recurrence of BC, in early prognosis.
Thyroid surgery is the most commonly performed procedure in the field of endocrine surgery. Studies are still ongoing on the development of a single algorithm for diagnosis and care of patients at risk of postoperative hypoparathyroidism. The aim of the study was to determine the biochemical marker that would allow the most accurate diagnosis of patient groups at risk of developing hypoparathyroidism and to identify risk factors for this disorder. MATERIAL AND METHODS: The prospective study included 142 consecutive patients undergoing total thyroidectomy for benign goiter from January 1st 2014 to December 31st 2015. Serum intact parathyroid hormone (iPTH), total calcium (Ca), phosphate (P), and magnesium (Mg) levels have been measured preoperatively and at 1, 6, 24, and 48 h postoperatively. RESULTS: Clinical symptoms of hypoparathyroidism developed in 25 (17.6%) of 142 patients. The best diagnostic accuracy for hypoparathyroidism based on ROC curves was obtained for iPTH at 6h (AUC 0.942; 95% CI: 0.866-1.000, p<0.001) and its percentage change from baseline ΔiPTH at 6h (AUC 0.930; 95% CI: 0.858-1.000, p<0.001). In an multivariate analysis, the preoperative Ca level higher by 0.1 mmol/l, and iPTH level higher by 0.1 pmol/l were associated with a lower risk of hypoparathyroidism, by 68% (p=0.012) and 61% (p=0.007), respectively. A 1% decline in iPTH from baseline increased the risk of hypoparathyroidism by 15% (p<0.001). CONCLUSIONS: The most reliable markers indicating a high risk of postoperative hypoparathyroidism are the decline in ΔiPTH at 6h by > 65% or iPTH level at 6h <1.57 pmol /l. A postoperative decline in iPTH levels is an independent risk factor for the development of hypoparathyroidism. Preoperative higher concentrations of Ca and iPTH are protective factors for the development of this disorder.
The inactivation of tumor suppressor genes located within 9p21 locus (CDKN2A, CDKN2B) occurs in up to 30% of children with B-cell precursor acute lymphoblastic leukemia (BCP-ALL), but its independent prognostic significance remains controversial. In order to investigate the prognostic impact of deletions and promoter methylation within 9p21, 641 children with newly diagnosed BCP-ALL using methylation specific multiplex ligation-dependent probe amplification (MS-MLPA) were investigated. A total of 169 (26.4%) microdeletions in 9p21 were detected, of which 71 were homozygous. Patients with CDKN2A homozygous deletions were older at diagnosis (p < .001), more frequently steroid resistant (p = .049), had higher WBC count (p < .001), higher MRD at Day 15 (p = .013) and lower relapse-free survival [p = .028, hazard ratio: 2.28 (95% confidence interval: 1.09–4.76)] than patients without these alterations. CDKN2A homozygous deletions coexisted with IKZF1 and PAX5 deletions (p < .001). In conclusion, CDKN2A homozygous deletions, but not promoter methylation, are associated with poor response to treatment and increased relapse risk of pediatric BCP-ALL.
Wstęp: Glejak wielopostaciowy (GB — glioblastoma) to najczęstszy i najgorzej rokujący nowotwór pierwotny OUN. W świetle braku wiarygodnych klinicznych czynników predykcyjnych w grupie chorych z tym rozpoznaniem oraz ze względu na dużą heterogenność molekularną przypadków GB, coraz większe znaczenie przypisuje się subklasyfikacji molekularnej glejaków wielopostaciowych. Niektóre odkrycia dotyczące biologii glejaków (metylacja genu MGMT czy kodelecja 1p/19q) już teraz umożliwiają wyodrębnienie grupy chorych z lepszym rokowaniem. Celem naszej pracy jest analiza wpływu wybranych czynników klinicznych i molekularnych na rokowanie u pacjentów z GB. Materiały i metody: Do badania włączono 277 chorych leczonych z powodu GB w łódzkich ośrodkach onkologicznych w latach 2001–2015. Opisaną kohortę poddano retrospektywnej analizie pod kątem wpływu wybranych czynników klinicznych oraz molekularnych na przeżycie pacjentów (OS). Wyniki: Grupę badaną stanowiło 119 kobiet (42,96%) i 158 mężczyzn (57,04%). Średni wiek pacjentów wynosił 58,3 ± 11,8 lat. Wyższa przedoperacyjna ocena w skali Karnofsky’ego wiązała się z lepszym rokowaniem u chorych: HR 0,91 (95% CI: 0,89–0,93); p < 0,001. Z kolei wyższy wiek przy rozpoznaniu okazał się być czynnikiem pogarszającym rokowanie — HR 1,05 (95% CI: 1,03–1,06); p < 0,001. Ponadto wykazaliśmy, że występowanie polisomii chromosomu 7 istotnie pogarszało rokowanie — HR 2,68 (95% CI: 1,24–5,79), p = 0,012. Omówienie: Ze względu na heterogenność GB konieczne jest dogłębne poznanie biologii tego nowotworu. Wyniki naszego badania sugerują, że nowoczesna klasyfikacja glejaków powinna brać pod uwagę zarówno czynniki kliniczne, jak i molekularne, co umożliwi lepszą diagnostykę oraz dostosowanie terapii w omawianej grupie chorych.
Wstęp: Toksyczność sercowa jest najważniejszym następstwem radioterapii raka piersi. W erze radioterapii planowanej trójwymiarowo ważne i możliwe jest oszacowanie dawek nie tylko w sercu, ale także w naczyniach wieńcowych czy jamach serca, a w przyszłości oszacowanie dawek tolerancji. Celem pracy było zakonturowanie wybranych struktur serca według atlasu kardiologiczego Mary Feng oraz RTOG, oszacowanie średnich dawek i odpowiedzenie na pytanie, czy istnieją zależności pomiędzy dawka średnią na serce a dawką na pozostałe zakonturowane struktury. Materiał i metody: Do badania włączono 15 chorych z wczesnym rakiem piersi lewej w stopniu zaawansowania I i IIA po chirurgicznym leczeniu oszczędzającym. Planowanie wykonano przy użyciu TK z kontrastem. Według atlasu kardiologicznego i RTOG doświadczony lekarz radioterapeuta zakonturował serce, lewą komorę — LV, lewą przednią tętnicę zstępującą — LAD, lewą tętnicę wieńcową — LMCA, prawą tętnice wieńcową — RCA, gałąź okalającą lewej tętnicy — LC oraz obszary anterior myocardial territory — AMT i anterior myocardium — AMC. U wszystkich pacjentek wykonano konformalne plany leczenia. Dawki porównano korelacją rang Spearmana, za istotne statystycznie przyjęto p < 0,05. Wyniki: Istnieje korelacja pomiędzy dawką średnią w LAD, LV i RCA a dawką średnią w sercu, AMT i AMC (dla wszystkich powyższych r > 0,4, p < 0,05). W przypadku LCA oraz LMCA nie wykazano istotnych statystycznie korelacji z dawką w sercu, AMT i AMC. Omówienie: Wykazaliśmy, że istnieje silna dodatnia korelacja pomiędzy średnią dawką na LAD, LV i RCA z dawką na serce, AMT i AMC. Nasze wyniki sugerują, że w przypadku trudności z zakonturowaniem naczyń wieńcowych, moż- na je zastąpić konturingiem serca, AMT lub AMC, które są strukturami łatwymi do zakonturowania nawet dla mało doświadczonego lekarza.
Wstęp: Badania randomizowane wskazują, że hipofrakcjonowana radioterapia jest tak samo skuteczną i bezpieczną metodą jak radioterapia konwencjonalna. W przypadku leczenia nowotworów piersi dodatkowym czynnikiem o szczególnym znaczeniu jest efekt kosmetyczny. Celem pracy jest ocena jakości życia i efektu kosmetycznego u pacjentek poddanych leczeniu hipofrakcjonowaną radioterapią. Materiał i metody: Przeanalizowano 78 chorych z rakiem piersi prawej w stopniu zaawansowania 0–IIA leczonych w latach 2014–2015. U pacjentek zastosowano konformalną, trójwymiarową tangencjalną radioterapię na obszar piersi, z podwyższeniem dawki w obszarze loży po guzie. Chore napromieniono do dawki 40,05 Gy w 15 frakcjach po 2,67 Gy 128 fotonami o energii 6 lub 15 MV. Dawkę w loży po guzie (10,0 Gy po 2,5 lub 2,0 Gy) podwyższano przy użyciu wiązki elektronów. Efekt kosmetyczny był oceniany raz w tygodniu w trakcie radioterapii, a po jej zakończeniu co 3 miesiące, oceny dokonywała chora oraz lekarz. Wyniki: Średnia wieku pacjentek włączonych do badania wynosiła 58,6 ± 18,9 roku. U większości chorych guz był zlokalizowany w kwadrancie górnym zewnętrznym. Wczesna reakcja skórna 1. stopnia wystąpiła u 44% (n = 34) chorych, 2. stopnia u 9% (n = 7), zwłóknienie u 26% (n = 20), obrzęk piersi u 13% (n = 10), hiperpigmentacja 1. stopnia u 56% (n = 44). W 91% (n = 71) efekt kosmetyczny oceniono jako znakomity lub dobry. Omówienie: U większości chorych efekt kosmetyczny był oceniony jako znakomity lub dobry. U tych pacjentek nie występowały odczyny późne. Gorszy efekt kosmetyczny powiązany był z kwadrantektomią i lokalizacją guza w kwadrantach wewnętrznych, szczególnie dolnym. Pacjentki jako główną zaletę radioterapii hipofrakcjonowanej podawały krótszy czas i bardzo dobrą tolerancję leczenia.
There is ongoing research with the goal of finding precise and sensitive biomarkers of multiple sclerosis (MS). Recently, researchers have paid particular attention to small, non-encoding, single stranded endogenous microRNA molecules (miR, miRNA). At first these molecules were thought to be found only within the cell. Today it is known, however, that they can also be found in the extracellular spaces (plasma, serum, saliva, urine, tears, sweat, milk, sperm and amniotic fluid, among others). It has been established that extracellular miRNA perform a wide spectrum of functions, such as transmitting signals between cells, modulating processes involved in angiogenesis, neurogenesis, proliferation or apoptosis. Given the high stability of these small molecules in the extracellular compartment (plasma), their tissue specificity and strong ties with pathological processes underlying multiple sclerosis, miRNA seem to be a good target for researchers trying to discover diseases’ new markers. Determining an accurate miRNA expression profile in MS and correlating it with the gene profile may lead to the discovery of new pathophysiological processes. Demonstrating that changes in the composition and concentration of extracellular miRNA may in some cases correlate with certain aspects of the underlying disease (such as its severity) could lead to their use as biomarkers of MS. Further research is needed.
Background NBN gene encodes nibrin which is a part of the MRN complex responsible for DNA double-strand brakes (DSB) repair. Homozygous mutation in NBN gene leads to rare autosomal recessive immunodeficiency associated with chromosomal instability and increased predisposition to lymphoproliferative disorders, called Nijmegen breakage syndrome (NBS). Although the role of homozygous deletion (657del5) of NBN gene in ALL development has been established, the impact of heterozygous variants of NBN gene on clinical course of childhood ALL remains undefined. Aims To determine clinical course and biological features of childhood ALL in homo- and heterozygous carriers of 657del5 mutation in NBN gene. Methods In total, 593 children (mean age 6.48±4.64 years, median follow-up 3.31 years) with newly diagnosed BCP-ALL treated in 15 centers of the Polish Pediatric Leukemia/Lymphoma Study Group were enrolled in the study. We detected 657del5 mutation in NBN gene using PCR with fluorescent primer and capillary electrophoresis. Positive results were subsequently confirmed by Sanger’s sequencing. Targeted copy number screening of selected 23 loci was performed on available DNA samples (n=366) using the P335-B2 SALSA MLPA kit (MRC-Holland, Netherlands). IKZF1 deletions were additionally identified using multiplex-PCR with breakpoint-specific primers. Survival analysis with estimation of the probability of overall survival (OS), event-free survival (EFS) and relapse-free survival (RFS) was performed with respect to cytogenetic and molecular features of ALL, clinical characteristics at diagnosis (WBC, age, gender, risk group, CNS involvement ) as well as response to treatment (steroidoresistance and minimal residual disease at day 15). Results In total, we identified n=23 patients (3.88%) with 657del5 in NBN gene, four of them (17.39%) harbouring biallelic deletions (Nijmegen breakage syndrome) while the remaining n=19 were heterozygous carriers (82.61%). Carriers of 657del5 in NBN had shorter EFS compared to wild type patients (median 2.05 years, IQR: 1.52-3.82 years vs. 3.16 years, IQR:1.89-4.79 years; p=0.082). No significant differences in OS were observed. Interestingly, we found that CNS relapse of BCP-ALL was significantly more frequent in 657del5 carriers as compare to wild-type patients (17.65% vs. 1.87%; p=0.002). In the multivariate analysis we found that steroidoresistance (OR=15.82, 95%CI 2.44-102.37, p=0.004) and being a carrier of 657del5 in NBN (OR=38.46, 95%CI 5.69-259.22, p<0.001) are independent risk factors increasing the risk of CNS relapse. Conclusion We report for the first time the association between NBN gene variants and biological and clinical features of childhood ALL. In our study cohort, carriers of 657del5 in NBN gene who were diagnosed with BCP-ALL had increased risk of CNS relapse regardless CNS involvement at diagnosis. Carriers of 657del5 have worse prognosis (shorter EFS) comparing to wild-type patients.
Purpose: An imbalance between matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) appears critical for tumor progression and metastasis. This study aimed to determine whether gene expression of MMP1, MMP2, MMP9, TIMP1 and TIMP3 and the MMP/TIMP expression ratio in peripheral blood leukocytes (PBLs) and the MMP1 and TIMP1 contents or MMP1/TIMP1 ratio in plasma were associated with clinicopathological characteristics in invasive ductal carcinoma (IDC) of the breast. Materials and methods: Blood samples were collected from women newly diagnosed with IDC who had not received prior treatment (n = 102). Gene expression in PBLs was analyzed by quantitative real-time polymerase chain reaction. Concentrations of MMP1 and TIMP1 in plasma were measured using ELISA. Results: In univariate analysis the expression levels of MMP2 and TIMP1 mRNA were significantly higher in premenopausal compared to postmenopausal patients (p<0.001 and p = 0.014, respectively). MMP2 mRNA expression negatively correlated with age (p<0.001, r = -0.43). We found that the MMP2/TIMP3 expression ratio was significantly higher in women after menopause (p = 0.007). The MMP2/TIMP1 expression ratio was higher in human epidermal growth factor receptor 2 (HER2)-positive patients (p = 0.022). Low-grade tumors had significantly lower MMP1/TIMP1 and MMP2/TIMP1 expression ratios (p = 0.047 and p = 0.048, respectively). TIMP1 plasma concentration was significantly higher in small tumors compared with T2-T3 tumors (p = 0.013). Conclusions: These findings reveal an important association between tumor characteristics and expression ratios of MMP1/TIMP1 and MMP2/TIMP1 in PBLs and TIMP1 concentration in plasma. Menopausal status may influence the mRNA expression levels of MMP2 and TIMP1 as well as the MMP2/TIMP3 expression ratio in IDC of the breast.
The authors present the anterior approach to cervical spine, which enabled complete resection of tumor located in the anterior part of the spinal canal. Considering there are not many reports in the literature, the authors present a case of a meningioma at the level C5–C6 resected with good result through anterolateral approach.
Introduction Neurofibromatosis type 2 (NF2) and schwannomatosis are entities that may, due to the similarity of clinical symptoms, cause diagnostic difficulties. Incidence rate of both diseases is similar and estimated between 1:25000 and 1:40,000. The genes associated with the development of the aforementioned disorders are in proximity and located on chromosome 22, although schwannomatosis is characterized by an incomplete penetrance and the risk of its transmission to the offspring is significantly lower than in the case of NF 2. Schwannomatosis clinical characteristic is similar to the NF2, however vestibular schwannomas are not present. Therefore the imaging studies evaluated by an experienced radiologist play a key role in the diagnostic process. Case report Forty two-year-old female hospitalized three times because of the tumors of the spinal canal was admitted to the Department of Neurosurgery and Peripheral Nerve Surgery in 2008 because of the cervical pain syndrome with concomitant headache. She was diagnosed with a schwannomatosis, recently distinguished, the third form of neurofibromatosis. MRI imaging revealed craniocervical junction tumor. Suboccipital craniectomy with concomitant C1–C2 laminectomy was done in order to remove the lesion. After the surgery the patient did not present any deficits in neurological examination and was discharged from hospital in good general condition. Conclusions The patient was diagnosed with schwannomatosis, recently established neurofibromatosis entity which may resemble NF2 clinically. In patients after the age of 30, in whom we observe multiple schwannomas without the concomitant hearing impairment, the diagnosis of schwannomatosis is very likely.
Introduction: It remains unclear how HbA1c recommendations influence metabolic control of paediatric patients with type 1 diabetes mellitus. To evaluate this we compared reported HbA1c with guideline thresholds. Materials and Methods: We searched systematically MEDLINE and EMBASE for studies reporting on HbA1c in children with T1DM and grouped them according to targeted HbA1c obtained from regional guidelines. We assessed the discrepancies in the metabolic control between these groups by comparing mean HbA1c extracted from each study and the differences between actual and targeted HbA1c. Results: We included 105 from 1365 searched studies. The median (IQR) HbA1c for the study population was 8.30% (8.00%–8.70%) and was lower in “6.5%” than in “7.5%” as targeted HbA1c level (8.20% (7.85%–8.57%) versus 8.40% (8.20%–8.80%);p=0.028). Median difference between actual and targeted HbA1c was 1.20% (0.80%–1.70%) and was higher in “6.5%” than in “7.5%” (1.70% (1.30%–2.07%) versus 0.90% (0.70%–1.30%), resp.; p<0.001). Conclusions: Our study indicates that the 7.5% threshold results in HbA1c levels being closer to the therapeutic goal, but the actual values are still higher than those observed in the “6.5%” group. A meta-analysis of raw data from national registries or a prospective study comparing both approaches is warranted as the next step to examine this subject further.
We divided Supplementary materials into five sections. The first two sections demonstrate the study design and search strategy. The third part presents the results for the comparisons of HbA1c and ∆HbA1c within pre-planned subgroups. The fourth part displays the results from the meta-analysis of ∆HbA1c with respect to HbA1c guideline values. Tabularized features of the studies included in the review along with references are included in the fifth part.
Background: Radiation toxicity is an important issue limiting the dose prescription during therapy planning. Study Aims: The aims of this study are to evaluate changes of cytokines in patients undergoing radiotherapy for non-small cell lung cancer (NSCLC) to establish changes of their levels and evaluate which of the markers: IL-6, TNF-alpha, LBP and CRP are specifically affected by radiation dose received by normal tissue. Materials/Patients and Methods: We evaluated 32 patients irradiated for NSCLC by means of 2.0 Gy/daily schemes with total target doses in the range of 60–74 Gy. Cytokines were measured before start of treatment, on the day of reaching the total dose of 20 Gy and at 40 Gy. Data from the 40 Gy timepoint were correlated with histogram parameters of the radiotherapy protocol. Two control groups: healthy people (n=26) and breast cancer patients (21 cases) after radical surgical procedures were used for comparison. ELISA kits were used for cytokine quantification (IL-6, TNF-a, LBP and CRP). Results: NSCLC group showed higher than healthy controls and breast cancer patients baseline levels of IL-6 (4.64 pg/ml vs 1.5 vs 2.5; p<0.001) and higher TNF-alpha (17.53 pg/ml vs 5.66 vs 6.97; p<0.001) and CRP (37.33 μg/ml vs 37.57 vs 36.92, p=0.006). No such differences were seen in LBP levels (116.08 μg/ml vs 36.63 vs 58.26; p=0.85). Levels of all cytokines did not change significantly during treatment of NSCLC patients: However, at the 40Gy time point, positive, significant correlations were noted for LBP and medium lung dose (r=0.41, p=0.034). CRP concentrations increased significantly along with medium oesophageal dose (r=0.4, p=0.03). No other cytokines showed such associations, suggesting specificity of the LBP reaction to lung irradiation and CRP reaction to oesophageal toxicity. Acknowlegements:This study was funded by INTER projectNo. 127/UD/SKILLS/2015
Wstęp: Miejsce polimorficzne rs3824662 zlokalizowane w genie GATA-3 zostało opisane jako locus podatności zachorowania na BCR-ABL1-like ALL, nowo wyodrębniony podtyp B-komórkowej ostrej białaczki limfoblastycznej. Cel: Celem badania jest analiza związku polimorfizmu w linii germinalnej oraz ekspresji genu GATA-3 w komórkach białaczkowych z profilem mikrodelecji oraz przebiegiem klinicznym BCP-ALL u dzieci. Materiał i metody: Do badania włączono 461 pacjentów (średnia wieku 8,6�4,9 roku; czas obserwacji 2,4�1,7 roku) z diagnozą BCP-ALL, leczonych protokołem ALL-IC BFM09 w 15 ośrodkach Onkologii i Hematologii Dziecięcej. Pacjentów z fuzją BCR/ ABL1, rearanżacjami MLL lub hipodiploidią wyłączono z analizy. Poziom choroby resztkowej (MRD) oceniono w 15. dobie terapii. Obecność delecji w genach: IKZF1, PAX5, RB1, EBF1, IL3RA, ETV6, CSF2RA, BTG, SHOX, CRLF2, IKZF3, CDKN2B, CDKN2A, mir31 zidentyfikowano metodą MLPA (n=457). Genotyp locus rs3824662 oznaczono sondami TaqMan (n=461). Poziom ekspresji genu GATA-3 oceniono metodą qPCR (n=81). Wyniki: Rozkład genotypów w badanej grupie: AA: n=28 (6%); CA: n=150 (33%); CC: n=283 (61%). Wariant AA był związany z wyższą ekspresją genu GATA-3 w porównaniu do CA i CC, średnia dCT wynosiła odpowiednio: -0,11; -1,68, -3,72 (p=0,04). Nosiciele genotypu AA (mediana 7,6 roku; IQR: 4,24–11,16 roku) byli starsi (p=0,02) w chwili rozpoznania w porównaniu z chorymi z wariantami CA (mediana 4,7 roku; IQR: 3,00–8,54 roku) i CC (mediana 4,4 roku; IQR: 2,76–7,53 roku). Nie wykazaliśmy istotnych różnic w poziomach leukocytozy oraz MRD. Analiza mikrodelecji wykazała współwystępowanie defektów klastra PAR1 obejmującego geny IL3RA, CSF2RA, SHOX, CRLF2, co jest związane późniejszym rozpoznaniem (mediana 6,6 lat; IQR: 3,28–10,63 roku) w porównaniu z pacjentami z pozostałymi defektami (mediana 4,29 roku; IQR: 2,80–7,61 roku), p=0,03, wśród osób z genotypem AA 34,78% ma delecje w PAR1, natomiast CA – 11,72%, a CC – 6,84%, p=0,0001. Wnioski: Ekspresja GATA-3 w komórkach białaczkowych jest związana z genotypem w locus rs3824662, u nosicieli genotypu AA częściej występują delecje w regionie pseudoautosomalnym 1 na chromosomie X (PAR1). Badanie finansowane przez NCBiR w ramach projektu LIDER/031/635/l-5/13/NCBR/2014.
Wstęp: Nibryna, będąca białkowym produktem genu NBN, wchodzi w skład kompleksu MRN odpowiedzialnego za naprawę pęknięć dwuniciowych DNA w komórkach. Zespół Nijmegen, dziedziczony w sposób autosomalny recesywny, wiąże się z fragmentacją nibryny na 2 niefunkcjonalne części i ponad 50-krotnie zwiększa ryzyko rozwoju zmian limfoproliferacyjnych, w szczególności chłoniaków nieziarniczych oraz ALL. Dane dotyczące wpływu wariantu heterozygotycznego są niejednoznaczne. Cel: Określenie częstości homo- i heterozygotycznej mutacji 657del5 oraz polimorfizmu 171 V genu NBN w populacji polskiej oraz ocena ich wpływu na przebieg kliniczny i biologię ALL u dzieci. Materiał i metody: Do badania włączono 500 pacjentów w wieku 6,88�4,90 roku leczonych w polskich ośrodkach onkohematologii dziecięcej. Z pobranego w dniu rozpoznania szpiku kostnego wyizolowane zostało DNA, które posłużyło do genotypowania w kierunku homo- i heterozygotycznej mutacji 657del5 (metodą analizy dyskryminacji fluorescencji) oraz polimorfizmu I171 V (metodą restriction fragment polimorphism; PCR-RFLP) genu NBN. Wyniki pozytywne zostały potwierdzone metodą bezpośredniego sekwencjonowania. Stopień zajęcia OUN przez białaczkę oceniany był wg kryteriów ALL IC BFM 2009. Wyniki: Zmiany o typie delecji pięciu nukleotydów w pozycji 657 stwierdzono u 28 chorych (5,6%), u czterech z nich były to delecje homozygotyczne, u pozostałych 24 – heterozygotyczne. Polimorfizm I171 V stwierdzono u 17 pacjentów (3,4%), u wszystkich zmiana miała charakter heterozygotyczny. Wykazano, że wznowa ALL w obrębie OUN występowała istotnie częściej u pacjentów będących nosicielami delecji w porównaniu z osobami z wariantem wild type (18,75% vs 2,74%; p=0,008). Podobna zależność występowała przy porównaniu pacjentów z wariantem polimorficznym (15,38% vs 2,10%, p=0,039). Nie stwierdzono, by zmiany w obrębie NBN istotnie częściej towarzyszyły zmianom w genach zaangażowanych w patogenezę ALL. Nie wykazano wpływu zmian w genie NBN na przeżycie pacjentów. Wnioski: Nosicielstwo zarówno wariantu 657del5, jak i polimorfizmu I171 V, predysponuje do częstszego występowania wznowy ALL w obrębie OUN. Ocenione w badaniu warianty w obrębie genu NBN są częstym zjawiskiem w polskiej populacji dzieci leczonych z powodu ALL.
BACKGROUND We investigated whether in young children with inadequately controlled type 1 diabetes and technical problems with continuous subcutaneous infusion of insulin at 100 units/mL the switch to insulin diluted to 10 units/mL (U10) can limit technical problems and improve glycemic control. SUBJECTS AND METHODS: Diluted U10 insulin was started in three children 3.8, 3.2, and 1.3 years old with a hemoglobin A1c (HbA1c) level (mean±SD) of 8.1±0.17% (65±1.7 mmol/mol) and insulin dose of 8.80±2.93 units/day. Patients were evaluated with continuous glucose monitoring (iPro™2; Medtronic Minimed, Northridge, CA) and a quality of life questionnaire (PedsQL™; www.pedsql.org/ ) and surveyed for pump-related problems at baseline and after 3 and 9 months of U10 insulin therapy. RESULTS: Continuous glucose monitoring records showed that glycemic variability assessed by SD and M100 decreased significantly (P=0.0085 and P=0.0482, respectively). HbA1c levels dropped to 7.3±1.00% (56±11.0 mmol/mol) after 3 months and to 6.7±0.55% (50±6.1 mmol/mol) after 9 months (P=0.12). Technical difficulties were minimized. CONCLUSIONS: These results suggest that the use of U10 insulin decreases glycemic variability and improves hampered pump therapy in young children with inadequately controlled type 1 diabetes.
To investigate the clinical correlates and prognostic utility of MMP, VEGF and TIMP genes expression in bladder cancer (BCa) recurrence. Expression of MMP1, MMP2, MMP9, VEGFA and TIMP1, TIMP3 was analyzed byqRT-PCR using SYBR Green in peripheral blood leukocytes (PBLs) of BCa patients at two time points (diagnosis (n=40), and firstrecurrence (n=40)) and an age-matched group of healthy controls (n=100). Plasma concentrations of MMP1 (pro- and active forms) were measured using ELISA in BCa patients. The expression of MMP1 mRNA was significantly lower in BCa patients with first recurrence compared to control (p=0.019). Expression of other genes did not differ significantly between the groups. MMP9 gene expression was associated with differentiation grade (p=0.043), with the highest expression in poorly differentiated tumors (G3) and was higher in smokers than in non-smokers (p=0.039) in BCa patients at diagnosis. The results at two time points showed that MMP9 and VEGFA genes expression was increased in patients with moderately differentiated BCa (p=0.029), and advanced pathologic stage (p=0.048), respectively. Moreover, gene expression of TIMP1 was increased for G3 (p=0.043), and was decreased for early recurrence (p=0.003). Our study suggests that the expression of MMP9 in PBLs of BCa patients at diagnosis is associated with the differentiation grade of the BCa, and smoking status. Genes expression of MMP9, VEGFA and TIMP1 in PBLs may play a pivotal role in regulation of progression of BCa. Additionally, TIMP1 gene expression may be important factor for early recurrence of BCa. Copyright © 2015. Published by Elsevier Inc.
Chemokines are cytokines that act selectively on cells and are capable of inducing selective migration of cells in vitro and in vivo. The term was first coined at the 3rd International Symposium on Chemotactic Cytokines in 1992. The name “chemokine” is a contraction of “chemotactic cytokine,” meaning that these molecules combine features of both cytokines and chemotactic factors. They are a family of low-molecular-mass proteins acting on specific membrane receptors. A cell’s overall sensitivity to chemotaxis depends on the expression profile of chemokine receptors. Atherosclerosis is essentially an excessive inflammatory and proliferative response to the damage of arterial walls. It takes place within the wall and leads to the formation of unstable atherosclerotic plaques. Many chemokines have been studied in terms of their role in the pathogenesis of an atheromatous plaque in the carotid arteries, both in animal models and with the use of human tissue. It seems that molecules that are the most involved in the formation of atheromas in the carotid arteries include: CCL2, CCL3, CCL4 and CCL5. However, reports are sometimes contradictory, and more research is needed. Finding a marker that could help predict the destabilisation of an atheromatous plaque would be a valuable addition to the standard diagnostic panel of tests used in both the diagnosis and monitoring of vascular pathologies.
Background Platelet hyperreactivity is a factor which contributes towards increased risk of cardiovascular events in adults with type 2 diabetes (T2DM). However, little is known about platelets’ disturbances among children with type 1 diabetes (T1DM). The aim of the study was to investigate whether platelets’ morphology or function are altered in children with type 1 diabetes, potentially predisposing them to cardiovascular events in the future. Methods The study group consisted of 389 children with T1DM during the 2008–2010 period. Patients with acute diabetes complications and ongoing infections were excluded from the study. An equinumerous (N = 389), age and sex-matched control group was assembled from children undergoing routine, minor surgical procedures in the same hospital. Platelet: count (PLT), mean volume (MPV), distribution width (PDW) and platelet large cell ratio (P-LCR) as well as HbA1c levels were measured. For statistical analysis we used Chi-square tests, the student’s t-test, one-way analysis of variance (ANOVA), the Pearson’s correlation coefficient and linear regression models in order to adjust for covariates. Results MPV, PDW and P-LCR were significantly higher among children with diabetes in comparison with the control group (MPV 10.47+/−0.85 fL vs 10.23+/−0.94 fL, p = 0.0007; PDW 12.09+/−1.80% vs 11.66+/−1.90%, p = 0.0032; P-LCR 28.21+/−6.15% vs 26.29+/−6.38%, p < 0.0001). PLT however, were shown to be similar (263.55+/−60.04 vs 268.77+/−65.78 103/μl; p = 0.5637). In both cases and controls age was inversely correlated with platelet count (for study group: r = −0.30, p < 0.0001; for control group: r = −0.34, p < 0.0001), positively correlated with MPVs (r = 0.20, p < 0.0001; r = 0.26, p < 0.0001), PDW (r = 0.25, p < 0.0001 and r = 0.24, p < 0.0001) and P-LCR (r = 0.26, p < 0.0001; r = 0.26, p < 0.0001). After adjustment for confounding factors, higher platelet counts were associated with poorer metabolic control (beta = 0.20; 0.0001). Conclusions Platelets of paediatric patients with T1DM show morphological evidence of hyperreactivity (higher MPV, PDW and P-LCR), while poorer metabolic control increases their number potentially predisposing the patients to future cardiovascular events.
Purpose/Objective(s) Prostate cancer is the most common cancer in men with constantly increasing incidence rates. Considering that radiation therapy (RTx) is accepted alternative to radical prostatectomy, evaluation of outcomes regarding to dose RTx and its techniques is extremely important. Materials/Methods The study group covered patients with localized prostate cancer treated initially with radical RTx between January 2005 and June 2012. Radiation therapy protocols and outcomes from the Regional Radiation therapy Center in Lodz were retrospectively analyzed. Patients were treated either with 3D conformal RTx or Image-Guided Modulated RTx (IMRT) with hypofractionation (2.6Gy/day) or standard fractionation (2Gy/Day). Total dose of radiation ranged between 65 and 76 Gy. Radiotoxicity was assessed using the RTOG scales. The assessment of factors modifying the course of RTx and their impact on overall survival (OS) was performed using multivariate proportional hazard regression adjusting for patient’s age, Gleason score and socioeconomic status (SES). Results During the analysed period patients underwent RTx in the Center. Complete clinical and outcome data was collected for 932 individuals. Mean age at RTx initiation was 67.4±6.9 years. Thirty-three patients (3.54%) had T1 stage tumor and 899 patients (96.46%) T2 stage cancer. Gleason score equal or greater than 7 was observed in 481 patients (51.61%). No significant baseline differences were noted for patient’s age, Gleason’s score or T classification (all p>0.05). Hypofractionated RTx was used in 586 (62.88%) and 346 patients (37.12%) received standard fractionation protocol. In 713 patients (76.5%) IMRT was applied, while in 219 patients (23.5%) 3D conformal RTx was the method of choice. The analysis showed that hypofractionation was a favorable prognostic factor for OS (HR 0.64, 95% CI = 0.41-0.98, p = 0.043). The use of IMRT also promoted better overall survival (HR 0.63, 95% CI = 0.41-0.96, p = 0.033). In addition, older age (HR 1.06, 95% CI = 1.02-1.09, p = 0.0007), higher Gleason’s score (HR 1.48, 95% CI = 1.28-1.73, p<0.0001) and lower SES (HR 1.60, 95% CI = 1.06-2.41, p = 0.024) were associated with worse prognosis. The frequency of late gastrointestinal events of any severity did not differ significantly between the IMRT and 3D conformal RTx (32.0% vs 32.2%; p = 1.00). Late genitourinary events of any severity was significantly reduced in the IMRT group (25.7% vs 46.7%; p = 0.01). Conclusions Despite a relatively short observation time, we showed that the use of IMRT and hypofractionation in radical prostate cancer treatment improve OS. Use of IMRT reduced the rate of late radiotoxicity reactions from the genitourinary system. Lower SES is a factor which may worsen outcomes of treatment in prostate cancer patients.
Multiple sclerosis (MS) is a common chronic neurological disorder of the central nervous system that leads to progressive disability. The disease usually affects people between 20 and 40 years of age, with women being affected twice as often. Despite many years of research, very little is known about its pathogenesis. There are four distinct clinical presentations, of which the most common are the relapsing-remitting, the secondary progressive and primary progressive courses. The pathogenesis of MS is a complicated process, involving the disruption of the blood–brain and blood–cerebrospinal fluid barriers, secondary hyperplasia of the astroglia, inflammation, and neurodegeneration in a broad sense, among others. The inflammatory process involving various subpopulations of inflammatory cells plays a major role in the development of the disease, especially in its early stages. Previous studies have indicated that the tumour necrosis factor alpha (TNF-α), a proinflammatory cytokine, is particularly involved in the process. Aim of the study: To assess levels of TNF-α in the plasma of patients suffering from MS both undergoing a relapse and in remission, to correlate its concentration with clinical parameters, and to determine whether TNF-α could potentially serve as a marker of MS progression. The relationship between plasma concentrations of TNF-α and the number of leukocytes and subpopulations was analyzed in an attempt to identify major sources of TNF-α in the plasma in MS patients. Material and methods: Thirty-seven MS patients formed study groups (20 in the relapse group, 17 in the remission group). Thirty healthy volunteers formed the control group. Four millilitres of venous blood were collected from each participant. The blood was centrifuged (5000 rpm, 20 min, 23ºC) until the plasma layer could be separated and stored at –80ºC until the testing. TNF-α concentrations were determined using the ELISA method. Results and conclusions: The preliminary results did not show a statistically significant increase in TNF-α levels in the plasma of MS patients, both in the relapse and the remission groups. A positive correlation was found between the clinical severity of MS (measured by the EDSS score) and TNF-α levels in remission and relapse groups. However, it was not statistically significant. In a subgroup of patients in remission with low plasma levels of TNF-α (<1 pg/ml), higher TNF-α concentrations correlated with greater disability (EDSS score). WBC counts were statistically significantly higher in patients undergoing a relapse compared to the joint group of MS patients in relapse and in remission. Preliminary findings of small studies indicate that TNF-α plasma concentrations could potentially reflect the activity of underlying pathological processes in MS. Further studies on larger groups of patients are necessary to confirm the hypothesis as well as in order to correlate TNF-α concentrations in blood and the cerebrospinal fluid.
According to the established medical knowledge, the atheromatous lesions occur in the arteries of large and medium diameter. Their presence in the aorta, arteries of extremities as well as extracerebral and coronal arteries is clinically relevant. The evolution of atherosclerotic plaques probably starts in the prenatal development, what may be proved by the presence of the fatty streaks in endothelium of coronal arteries in some newborns. Then it evolves through lipid accumulation, media inflammatory response, vasa vasorum proliferation, fibrination and calcification of plaques. Researches proved that the matter of atherosclerosis is exaggerated inflammatory proliferative reaction to the arterial wall damage. The oxidative stress phenomenon and infections with common pathogens play an undoubtful role in this process. Ultimately the direct damage is an effect of immune response cells infiltration and secretion of cytokines and proinflammatory factors. Among the cells of immune system responsible for formation and development of atheromatous plaque are considered: macrophages, dendritic cells, T and B lymphocytes, monocytes. Attention was also paid to the inflammatory mediators and growth factors. Scientist are interested in unstable atherosclerotic plaque and accompanying inflammatory process within the artery wall for a long time. Meanwhile, there are conducted researches on inflammation markers underlying the destabilisation of plaques. Revealing the role of these cells in evolution of atherosclerosis would enable more complex understanding of the mechanism of lesions development. Then it would facilitate an introduction of the new and upgraded methods of treatment and prevention. Also the progress of imaging examinations is meaningful for diagnostics and treatment. It is contributory to the choice of therapeutic strategy and assessment of surgical intervention urgency. In the clinical practice there are recognized standards of imaging the morphology of atheromatous plaque. Development of diagnostics aims the indirect assessment of possible dynamics of lesions progression. Targeting the complex plaque analysis is based on excellence of established standards such as ultrasound examination or computed tomography.
Hearing is one of the most important human senses closely associated with the organ of hearing and balance. Patients with sudden hearing loss sometimes report ear fullness, tinnitus or vertigo. Hearing disturbances is a very unpleasant sensation lowering the quality of life. Sudden hearing loss is mostly caused by otologic diseases but also disturbances of brain circulation, brain injury, viral (mumps, rubella, herpes zoster) and bacterial infections, bone diseases, bone tumours, 8th nerve tumours, genetic disorders, autoimmune diseases (e.g. multiple sclerosis), ototoxic medications and many others. Hearing disorders are generally divided into central and peripheral, the latter divided into conductive and perceptive. Deafness is a worrying symptom not only for the patient but also for a clinical neurologist. Diagnosis is based on the past history, physical examination, both otolaryngological and neurological, diagnostic investigations, audiological investigation, atrial excitability testing (caloric tests, electronystagmography) depending on clinical indications, neuroradiological investigations, brainstem auditory evoked potentials, blood tests and others, which enables instituting a proper treatment.
Background / Purpose: Vascular occlusion and cardiovascular events in adult diabetic population are associated with platelet hyperactivity. There is not enough evidence considering effects of diabetes on platelets in children with type 1 (T1DM). Main conclusion: Platelets of diabetic children have greater volume, are more anisotropic and probably more functionally active (as evidenced by P-LCR) in comparison with healthy controls. Poorer metabolic control was associated with even greater increases in platelet count and their volume hinting at an increased risk of cardiovascular complications.
Question - Rkg
I am a "rookie" and I am just beginning my adventure with microRNAs. Recently I've come across some interesting presentations on this subject (links below). I hope they will also help you.
Awards & Achievements (3)
Scholarship · Apr 2014
Scholarship: Scholarship of Marshal of Łódź Voivodeship
Scholarship · Dec 2013
Scholarship: Scholarschip of Ministry of Science and Higher Education for achievements in science
Scholarship · Dec 2012
Scholarship: Scholarschip of Ministry of Science and Higher Education for achievements in science