Clinicopathological significance of the EMT-related proteins and their interrelationships in prostate cancer. An immunohistochemical study.

The chronic inflammation influences a microenvironment, where as a result of losing control over tissue homeostatic mechanisms, the carcinogenesis process may be induced. Inflammatory response cells can secrete a number of factors that support both initiation and progression of cancer and also they may consequently induct an epithelial-mesenchymal transition (EMT), the process responsible for development of distant metastasis. Macrophage migration inhibitory factor (MIF) acts as a pro-inflammatory cytokine that is considered as a link between chronic inflammation and tumor development. MIF can function as a modulator of important cancer-related genes expression, as well as an activator of signaling pathways that promotes the development of prostate cancer. The study was performed on FFPE tissues resected from patients who underwent radical prostatectomy. To investigate the relationship of studied proteins with involvement in tumor progression and initiation of epithelial-to-mesenchymal transition (EMT) process, we selected clinicopathological parameters related to tumor progression. Immunohistochemical analyses of MIF, SOX-4, ß-catenin and E-cadherin were performed on TMA slides. We found a statistically significant correlation of overall ß-catenin expression with the both lymph node metastasis (p<0.001) and presence of angioinvasion (p = 0.012). Membrane ß-catenin expression was associated with distant metastasis (p = 0.021). In turn, nuclear MIF was correlated with lymph node metastasis (p = 0.003). The positive protein-protein correlations have been shown between the total ß-catenin protein expression level with level of nuclear SOX-4 protein expression (r = 0.27; p<0.05) as well as negative correlation of ß-catenin expression with level of nuclear MIF protein expression (r = -0.23; p<0.05). Our results seem promising and strongly highlight the potential role of MIF in development of nodal metastases as well as may confirm an involvement of ß-catenin in disease spread in case of prostate cancer.

The prognostic value of leucine-rich repeat-containing G-protein (Lgr5) and its impact on clinicopathological features of colorectal cancer.

INTRODUCTION: Colorectal cancer (CRC) constitutes one of the most prevalent malignancies in the world. Recent research suggests that cancer stem cells (CSCs) are responsible for tumor cell's malignant behavior in CRC. This study has been designed to determinate clinical implications of CSC markers: CD44, DCLK1, Lgr5, and ANXA2 in CRC. MATERIALS AND METHODS: The study was performed on tissue samples which were collected from 89 patients undergoing colectomy. Formalin-fixed paraffin-embedded tissue blocks with representative tumor areas were identified and corded. Immunohistochemical staining was performed using anti-CD44, anti-LGR5, anti-ANXA2, and anti-DCLK1 antibodies. The H-score system was utilized to determine the immunointensity of CRC cells. RESULTS: The lower expression of Lgr5 was significantly correlated with the presence of lymph-node metastases (p = 0.011), while high expression of Lgr5 was statistically significant in vascular invasion in examined cancer tissue samples (p = 0.027). Moreover, a high H-score value of Lgr5 expression was significantly related to a reduced overall survival rate (p = 0.043). CONCLUSION: Our results suggest a strong relationship between CSC marker Lgr5 and vascular invasion, presence of lymph-node metastasis, and overall poor survival. The presence of Lgr5 might be an unfavorable prognostic factor, and its high level in cancer tissue is related to an aggressive course. This marker could also be used to access the effectiveness of the treatment.

Real-world effectiveness of abobotulinumtoxinA (Dysport®) in adults with upper limb spasticity in routine clinical practice: an observational study.

AbobotulinumtoxinA (aboBoNT-A, Dysport®) is used in clinical practice as a well-tolerated and effective therapy for muscle spasticity. AboBoNT-A has been shown to reduce upper and lower limb spastic paresis in clinical trials, demonstrating improvements in muscle tone and limb function. This open-label, multicentre, observational, non-interventional study was the first to investigate aboBoNT-A's efficacy in adult patients with upper limb spasticity (ULS) in routine clinical practice in Poland. All enrolled patients received ≥1 aboBoNT-A injection cycles, per routine clinical practice (full analysis set, FAS), and ≥1 rehabilitation session. Patients attended a baseline visit (V1) and two follow-up visits (V2, V3) for retreatment, depending on the investigator's assessment of individual patient needs, with a mean interval (SD) between injections of 4.4 (1.4) and 4.5 (1.2) months. The primary effectiveness endpoint was patient- and physician-based evaluation using the Clinical Global Impression-Improvement Scale (CGII), a validated 7-point scale (1 = very much improved to 7 = very much worse) relative to baseline. CGI-I has not previously been used as a primary endpoint in studies evaluating ULS. Secondary endpoints included muscle tone in shoulder, elbow, carpal joint, and finger muscles, measured by the Modified Ashworth Scale (MAS), and muscle strength according to the Medical Research Council scale (MRC). Of 108 enrolled patients (FAS), 92 (85.2%) completed the study and 57 (52.8%) were included in the per protocol (PP) population. AboBoNT-A improved patient conditions in 96.4% and 98.6% at V2 and V3 (investigator assessment) and 92.8% and 98.6% (as reported by patient) of patients, respectively. Significant reductions in muscle tone from baseline were observed at both visits (p < 0.0001-0.0077) across muscle groups. Increased muscle strength by cumulative MRC was observed at V2 (p = 0.0566) and V3 (p = 0.0282) versus baseline. Safety was consistent with the known profile of aboBoNT-A. In conclusion, aboBoNT-A treatment is beneficial in patients with post-stroke ULS in routine clinical practice, assessed by patients and investigators.

Effect of acetylsalicylic acid intake on platelet derived microvesicles in healthy subjects.

Platelet-derived microvesicles (pMVs) are released from platelets in physiological and pathological conditions and exhibit a wide range of prothrombotic, antithrombotic, proatherogenic, and pro-inflammatory properties. Antiplatelet agents, such as acetylsalicylic acid (ASA), are widely used for the prevention and treatment of vascular diseases, but their impact on pMV release remains poorly understood and contradictory mainly because of discrepancies in the methodology and lack of well-standardized MV assessment protocols. The present study investigated the effects of ASA not only on total pMV release but also on their phenotypes defined using the surface expression of pro-inflammatory (CD40L, CD62P, CD31) and procoagulant (PS, PAC-1) markers in healthy subjects. Fifty healthy volunteers were enrolled in the study and received a daily dose of 150 mg ASA for 3 consecutive days. Circulating pMVs were characterized and quantified before and after the intervention period using flow cytometry. Serum levels of thromboxane B2 (TXB2) and whole blood impedance platelet aggregation under arachidonic acid (AA) stimulation were also investigated to assess ASA compliance. In general, ASA did not effect pMV numbers in healthy subjects despite its effective inhibition of platelet aggregation Moreover, in premenopausal women, we noticed an increase in the number of pMVs. Further studies are needed to assess whether dose modification of ASA or combinations or changes in antiplatelet therapy would reduce pMV formation, especially in patients with cardiovascular risk factors.

Association of platelet-derived microvesicles and their phenotypes with carotid atherosclerosis and recurrent vascular events in patients after ischemic stroke.

INTRODUCTION: Platelet-derived microvesicles (pMVs) exhibit procoagulant and proinflammatory properties and play a role in the development and progression of atherosclerosis. The study examined the association between the total number of pMVs and their phenotypes with carotid atherosclerosis and recurrent vascular events (VEs) in patients in the convalescent phase of ischemic stroke (IS). MATERIALS AND METHODS: The study group consisted of 72 patients with IS secondary to large artery atherosclerosis (LAA) (n = 40) and small arteries occlusion (SAO) (n = 32) and 69 matched cardiovascular disease risk-factor (RF) controls. Total pMV number, defined as CD61+ microvesicles (MVs), and their phenotypes, defined as the surface expression of proinflammatory (CD40L, CD62P, CD31) and procoagulant (PS, PAC-1) markers, were characterized and quantified using flow cytometry. The mean common carotid intima-media thickness (CCA mean IMT), maximal common carotid IMT (CCA max IMT) and maximal bifurcation IMT (BIF max IMT) were measured bilaterally using B-mode, color Doppler ultrasonography. All study subjects were observed for one-year to establish the occurrence of VEs. RESULTS: No differences in pMV parameters between LAA and SAO stroke subjects and between stroke subgroups and controls were found. Stroke patients with carotid atherosclerosis exhibited higher concentration of CD62P+/CD61+ and PAC-1+/CD61+ MVs compared to patients without the atherosclerosis. Positive associations between total number of pMVs, AnV+ MVs and AnV+/CD61+ MVs and atherosclerotic thickening of carotid intima-media in stroke patients were found. Elevated concentration of AnV+/CD61+, PAC-1+/CD61+, CD61P+/CD61+ and CD31+/CD61+ MVs, were revealed in stroke patients who suffered from recurrent VE in one-year follow-up period. Negative correlation of pMVs and CD62P+/CD61+ MVs concentration as well as percentage of total CD61+ in AnV+ population of MVs and time elapsed from IS in convalescent stroke subjects was revealed. CONCLUSION: Our results confirm positive correlations between total pMV number, the number of PAC-1+/CD61+ and CD62+/CD61+ MVs and carotid atherosclerosis in stroke subjects. Some pMV parameters may exhibit a predictive value for the next VE in groups with a history of stroke. pMVs and some of their phenotypes decline over time elapsed from stroke in convalescent stroke subjects.

Association of platelet-derived microvesicles with high on-treatment platelet reactivity in convalescent ischemic stroke patients treated with acetylsalicylic acid

Introduction: Elevated concentrations of platelet-derived microvesicles are found in cerebrovascular diseases. The impact of acetylsalicylic acid on these microvesicles remains inconsistent, despite its well-established effect on platelet aggregation. High residual platelet aggregation is defined as high on-treatment platelet reactivity, while "treatment failure" is the occurrence of vascular events despite antiplatelet treatment. The aim of this study was to determine whether the antiaggregatory effect of acetylsalicylic acid correlates with platelet-derived microvesicles in convalescent ischaemic stroke patients and cardiovascular risk factor controls as well as to evaluate the association between high on-treatment platelet reactivity and recurrent vascular events with the studied platelet-derived microvesicle parameters. Material and methods: The study groups consisted of 76 convalescent stroke patients and 74 controls. Total platelet-derived microvesicles, annexino-positive microvesicles number, and platelet-derived microvesicles with surface expression of proinflammatory (CD40L, CD62P, CD31) and procoagulant (PS, GPIIb/IIIa) markers were characterized and quantified using flow cytometry. Cyclooxygenase-1-specific platelet responsiveness, with whole blood impedance platelet aggregation under arachidonic acid stimulation and the serum concentration of thromboxane B2, were evaluated. Results: Neither acetylsalicylic acid intake nor modification of its daily dose caused statistically significant differences in the studied microvesicle parameters. Additionally, no statistically significant differences in the studied microvesicle parameters were revealed between high on-treatment platelet reactivity and non-high on-treatment platelet reactivity subjects in either study subgroup. However, elevated concentrations of PAC-1+/CD61+, CD62P+/CD61+ and CD31+/CD61+ microvesicles were found in stroke patients with treatment failure, defined in this study as a recurrent vascular events in a one-year follow-up period. Conclusions: This study revealed no relationship between circulating microvesicle number and platelet aggregation. The procoagulant and proinflammatory phenotype of circulating platelet-derived microvesicles might contribute to acetylsalicylic acid treatment failure.

[Tobacco smoking and HPV infection]. / Palenie tytoniu a zakazenie HPV.

Cervical cancer is one of the most common neoplasm in women in Poland. Etiopathogenesis of this neoplasm is mainly related to HPV infections. The persistent HPV infection is an important but not the only one sufficient factor in neoplastic transformation. The additional factors include tobacco smoking. Nowadays, prophylactic programs are conducted as cytologic screening, sexual education as well as decreased tobacco smoking. The aim of the present paper was the evaluation of correlation of number of smoked cigarettes and duration of smoking habit with histopathological changes uterine cervix. From 143 women operated due to gynecological problems there were selected 21 cases (medium age 44 years) with cervical cancer. In 5 women preoperative brachytherapy was done. E used immunohistochemical methods (with LSAB system) for evaluation of presence of L1 protein of HPV. The correlation between the stage of neoplasm and presence of viral protein was impossible as clinical records missed the information on tobacco smoking. In conclusion we would like to stress that evaluation of the possible role of proved and possible neoplastic factors needs a preparation of proper databases.

[Is low pre-pregnancy body mass index a risk factor for preterm birth and low neonatal birth weight?]. / Niski BMI przed zajsciem w ciaze: czy jest czynnikiem ryzyka porodów przedwczesnych i niskiej masy urodzeniowej noworodków?

OBJECTIVES: A pregnant woman's weight is an extremely important factor in the course of pregnancy and delivery. Not only obesity but also being underweight may lead to complications in pregnancy such as: preterm delivery and low neonatal birth weight. DESIGN: The aim of this study was to analyze the relationship between a low BMI and outcome of pregnancy, birth weight and general well being of the neonates. MATERIAL AND METHODS: 415 patients who were hospitalized in the Department of Obstetrics and Reproduction Wroclaw Medical University between 1996-2005 was done. The patients were divided into 3 groups I--Underweight (BMI <19,8), II--Appropriate weight (BMI 19,8-26,0) and III--Overweight (BMI>26,0). RESULTS: The frequency of preterm deliveries as well as low neonatal birth weight <2500g, in underweight mothers was higher than in other groups. CONCLUSIONS: Low pre-pregnancy BMI is an important factor risk factor in preterm deliveries. There was no correlation between BMI and the general well being of the neonates.