Association between skin lymphangiogenesis parameters and arterial hypertension status in patients: An observational study.

BACKGROUND: Recent studies have indicated that the skin lymphatic system and interstitium may play a role in the pathophysiology of arterial hypertension (AH). OBJECTIVES: We aimed to determine whether the set of pathway parameters described previously in rodents would allow for the distinction between hypertensive and normotensive patients. MATERIAL AND METHODS: Molecular and histopathological parameters from the skin and blood of patients with AH (AH group, n = 53), resistant AH (RAH group, n = 32) and control (C group, n = 45) were used, and a statistical multivariate bootstrap methodology combining partial least squares-discriminant analysis (PLS-DA) and selectivity ratio (SR) were applied. RESULTS: The C vs RAH model presented the best prediction performance (AUC test = 0.90) and had a sensitivity and specificity of 73.68% and 83.33%, respectively. However, the parameters selected for the C vs AH group model were the most important for the pathway described in the rodent model, i.e., greater density of the skin lymphatic vessels (D2-40 expression) and greater number of macrophages (CD68 expression), higher expression of the messenger ribonucleic acid (mRNA) of nuclear factor of activated T cells 5 (NFAT5), vascular endothelial growth factor C (VEGFC) and podoplanin (PDPN) in the skin, greater concentration of hyaluronic acid (HA) in the skin, and lower serum concentration of VEGF-C. CONCLUSIONS: Our study suggests that the NFAT5/VEGF-C/lymphangiogenesis pathway, previously described in rodent studies, may also be present in human HA. Further experiments are needed to confirm our findings.

Impaired Expression of the Salvador Homolog-1 Gene Is Associated with the Development and Progression of Colorectal Cancer.

Salvador homolog-1 (SAV1) is a component of the Hippo pathway that regulates tissue growth and homeostasis by affecting diverse cell processes, including apoptosis, cell division, and differentiation. The aberrant expression of Hippo pathway components has been observed in various human cancers. This study aimed to examine the expression level of the SAV1 gene in colorectal cancer (CRC) and its prognostic value and associations with tumor progression. We obtained matched pairs of tumor tissue and non-cancerous mucosa of the large intestine from 94 CRC patients as well as 40 colon biopsies of healthy subjects collected during screening colonoscopy. The tissue samples and CRC cell lines were quantified for SAV1 mRNA levels using the quantitative polymerase chain reaction method, while SAV1 protein expression was estimated in the paired tissues of CRC patients using immunohistochemistry. The average level of SAV1 mRNA was decreased in 93.6% of the tumor tissues compared to the corresponding non-cancerous tissues and biopsies of healthy colon mucosa. A downregulated expression of SAV1 mRNA was also noted in the CRC cell lines. Although the average SAV1 immunoreactivity was increased in the CRC samples compared to the non-cancerous tissues, a decreased immunoreactivity of the SAV1 protein in the tumor specimens was associated with lymph node involvement and higher TNM disease stage and histological grade. The results of our study suggest that the impaired expression of SAV1 is involved in CRC progression.

Sodium accumulation in the skin is associated with higher density of skin lymphatic vessels in patients with arterial hypertension.

PURPOSE: Recent studies, conducted mainly on the rodent model, have demonstrated that regulatory pathway in the skin provided by glycosaminoglycans, nuclear factor of activated T cells 5 (NFAT5), vascular endothelial growth factor C (VEGF-C) and process of lymphangiogenesis may play an important role in extrarenal regulation of sodium (Na+) balance, body water volume, and blood pressure. We aimed to investigate the concentrations and relations among the main factors of this pathway in human skin to confirm that this regulatory axis also exists in humans. PATIENTS AND METHODS: Skin specimens from patients diagnosed with arterial hypertension and from control group were histologically and molecularly examined. RESULTS: The primary hypertensive and control groups did not differ in Na+ â€‹concentrations in the skin. However, the patients with hypertension and higher skin Na+ concentration had significantly greater density of skin lymphatic vessels. Higher skin Na+concentration was associated with higher skin water content. In turn, skin water content correlated with factors associated with lymphangiogenesis, i.e. NFAT5, VEGF-C, and podoplanin (PDPN) mRNA expression in the skin. The strong mutual pairwise correlations of the expressions of NFAT5, VEGF-C, vascular endothelial growth factor D (VEGF-D) and PDPN mRNA were noted in the skin in all of the studied groups. CONCLUSIONS: Our study confirms that skin interstitium and the lymphatic system may be important players in the pathophysiology of arterial hypertension in humans. Based on the results of our study and existing literature in this field, we propose the hypothetical model which might explain the phenomenon of salt-sensitivity.

Effects of the Foam Massage Roller on VEGF-A and FGF-2 Blood Levels in Young Men.

BACKGROUND/AIM: Angiogenesis induced in muscles or massaged tissue is thought to support their regeneration and performance. Therefore, different methods that could promote angiogenesis are investigated. The aim of this study was to examine whether the use of the foam roller massager for lower limb muscles affects VEGF-A and FGF-2 levels in young men. MATERIALS AND METHODS: The study group included 60 healthy young men attending Military University of Land Forces, Wroclaw, Poland. The participants were randomly divided into two groups. The experimental group included 40 individuals who performed self-massage of the lower limbs using a foam roller. The control group comprised 20 individuals who did not perform massage. Massage was applied to lower limb muscles four times a week for seven weeks. Blood was collected before the experiment and after weeks 1, 3, 5, and 7. ELISA was used to determine changes in VEGF-A and FGF-2 levels in blood serum. RESULTS: The results of the study demonstrated a significant increase in VEGF-A serum levels in the group of individuals who underwent massage each week compared to VEGF-A concentrations before the experiment. The increase in VEGF-A levels in the experimental group was observed throughout the experiment compared to the control group. No significant changes in serum FGF-2 levels were found. CONCLUSION: The use of a foam massage roller increased VEGF-A serum levels, which may indicate stimulation of angiogenesis.

BCL11A Expression in Non-Small Cell Lung Cancers.

B-cell leukemia/lymphoma 11A (BCL11A) may be one of the potential biomarkers of non-small cell lung cancer (NSCLC). However, its role in the development of this cancer has not yet been precisely established. The aim of this study was to investigate the expression of BCL11A at the mRNA and protein levels in NSCLC cases and non-malignant lung tissue (NMLT) and to determine the relationship between BCL11A expression and the clinicopathological factors and Ki-67, Slug, Snail and Twist. The localization and the level of BCL11A protein were examined using immunohistochemistry (IHC) on 259 cases of NSCLC, and 116 NMLT samples were prepared as tissue microarrays and using immunofluorescence (IF) in the following cell lines: NCI-H1703, A549 and IMR-90. The mRNA expression of BCL11A was determined using real-time PCR in 33 NSCLC cases, 10 NMLT samples and the cell lines. BCL11A protein expression was significantly higher in NSCLC cases compared to NMLT. Nuclear expression was found in lung squamous cell carcinoma (SCC) cells, while cytoplasmic expression was demonstrated in adenocarcinoma (AC) cells. Nuclear expression of BCL11A decreased with increasing malignancy grade and correlated positively with Ki-67 and Slug and Twist expression. The opposite relationships were found for the cytoplasmic expression of BCL11A. Nuclear expression of BCL11A in NSCLC cells may affect tumor cell proliferation and change their phenotype, thus promoting tumor progression.

The Role of Irisin/FNDC5 Expression and Its Serum Level in Breast Cancer.

Irisin (Ir) is an adipomyokine formed from fibronectin type III domain-containing protein 5 (FNDC5), which can be found in various cancer tissues. Additionally, FNDC5/Ir is suspected of inhibiting the epithelial-mesenchymal transition (EMT) process. This relationship has been poorly studied for breast cancer (BC). The ultrastructural cellular localizations of FNDC5/Ir were examined in BC tissues and BC cell lines. Furthermore, we compared serum levels of Ir with FNDC5/Ir expression in BC tissues. The aim of this study was to examine the levels of EMT markers, such as E-cadherin, N-cadherin, SNAIL, SLUG, and TWIST, and to compare their expression levels with FNDC5/Ir in BC tissues. Tissue microarrays with 541 BC samples were used to perform immunohistochemical reactions. Serum levels of Ir were assessed in 77 BC patients. We investigated FNDC5/Ir expression and ultrastructural localization in MCF-7, MDA-MB-231, and MDA-MB-468 BC cell lines and in the normal breast cell line (Me16c), which was used as the control. FNDC5/Ir was present in BC cell cytoplasm and tumor fibroblasts. FNDC5/Ir expression levels in BC cell lines were higher compared to those in the normal breast cell line. Serum Ir levels did not correlate with FNDC5/Ir expression in BC tissues but were associated with lymph node metastasis (N) and histological grade (G). We found that FNDC5/Ir correlated moderately with E-cadherin and SNAIL. Higher Ir serum level is associated with lymph node metastasis and increased grade of malignancy. FNDC5/Ir expression is associated with E-cadherin expression level.

BCL11A Expression in Breast Cancer.

B-cell leukemia/lymphoma 11A (BCL11A) is a transcription factor that regulates the expression of genes involved in cell division or apoptosis. A link between high BCL11A expression and a worse prognosis has been demonstrated in patients with various cancers. The aim of this study was to investigate the expression pattern of BCL11A in breast cancer (BC) cases and mastopathy samples and to correlate the results with the clinicopathological data. The expression of the BCL11A protein was investigated using immunohistochemistry (IHC) on 200 cases of BC and 13 mastopathy samples. The level of BCL11A mRNA was determined using real-time PCR in 22 cases of BC and 6 mastopathy samples. The expression of BCL11A was also examined at the protein and mRNA levels in BC cell lines. A higher expression level of BCL11A in BC cases was shown compared to mastopathy samples. The expression level of BCL11A in BC cases and in the studied cell lines decreased with the increasing grade of histological malignancy (G). It was also negatively correlated with the primary tumor size. A significantly lower expression of BCL11A was found in BC that did not express estrogen or progesterone receptors and in triple-negative cases. The results of our research suggest that BCL11A may be relevant in the development of BC.

Expression of RBMS3 in Breast Cancer Progression.

The aim of the study was to evaluate the localization and intensity of RNA-binding motif single-stranded-interacting protein 3 (RBMS3) expression in clinical material using immunohistochemical (IHC) reactions in cases of ductal breast cancer (in vivo), and to determine the level of RBMS3 expression at both the protein and mRNA levels in breast cancer cell lines (in vitro). Moreover, the data obtained in the in vivo and in vitro studies were correlated with the clinicopathological profiles of the patients. Material for the IHC studies comprised 490 invasive ductal carcinoma (IDC) cases and 26 mastopathy tissues. Western blot and RT-qPCR were performed on four breast cancer cell lines (MCF-7, BT-474, SK-BR-3 and MDA-MB-231) and the HME1-hTERT (Me16C) normal immortalized breast epithelial cell line (control). The Kaplan-Meier plotter tool was employed to analyze the predictive value of overall survival of RBMS3 expression at the mRNA level. Cytoplasmatic RBMS3 IHC expression was observed in breast cancer cells and stromal cells. The statistical analysis revealed a significantly decreased RBMS3 expression in the cancer specimens when compared with the mastopathy tissues (p < 0.001). An increased expression of RBMS3 was corelated with HER2(+) cancer specimens (p < 0.05) and ER(-) cancer specimens (p < 0.05). In addition, a statistically significant higher expression of RBMS3 was observed in cancer stromal cells in comparison to the control and cancer cells (p < 0.0001). The statistical analysis demonstrated a significantly higher expression of RBMS3 mRNA in the SK-BR-3 cell line compared with all other cell lines (p < 0.05). A positive correlation was revealed between the expression of RBMS3, at both the mRNA and protein levels, and longer overall survival. The differences in the expression of RBMS3 in cancer cells (both in vivo and in vitro) and the stroma of breast cancer with regard to the molecular status of the tumor may indicate that RBMS3 could be a potential novel target for the development of personalized methods of treatment. RBMS3 can be an indicator of longer overall survival for potential use in breast cancer diagnostic process.

The Expression of Testin, Ki-67 and p16 in Cervical Cancer Diagnostics.

Testin is a protein expressed in normal human tissues, being responsible, with other cytoskeleton proteins, for the proper functioning of cell−cell junction areas and focal adhesion plaques. It takes part in the regulation of actin filament changes during cell spreading and motility. Loss of heterozygosity in the testin-encoding gene results in altered protein expression in many malignancies, as partly described for cervical cancer. The aim of our study was the assessment of the immunohistochemical (IHC) expression of testin in cervical cancer and its analysis in regard to clinical data as well the expression of the Ki-67 antigen and p16 protein. Moreover, testin expression was assessed by Western blot (WB) in commercially available cell lines. The IHC analysis disclosed that the expression of testin inversely correlated with p16 (r = −0.2104, p < 0.0465) and Ki-67 expression (r = −0.2359, p < 0.0278). Moreover, weaker testin expression was observed in cancer cases vs. control ones (p < 0.0113). The WB analysis of testin expression in the cervical cancer cell lines corresponded to the IHC results and showed a weaker expression compared to that in the control cell line. When we compared the expression of testin in cervical cancer cell lines, we found a weaker expression in HPV-negative cell lines. In summary, we found that the intensity of testin expression and the number of positive cells inversely correlated with the expression of Ki-67 (a marker of proliferation) and p16 (a marker of cell cycle dysregulation). This study shows that the combined assessment of testin, Ki-67 and p16 expression may improve cervical cancer diagnostics.

Role of RBMS3 Novel Potential Regulator of the EMT Phenomenon in Physiological and Pathological Processes.

RNA-binding protein 3 (RBMS3) plays a significant role in embryonic development and the pathogenesis of many diseases, especially cancer initiation and progression. The multiple roles of RBMS3 are conditioned by its numerous alternative expression products. It has been proven that the main form of RBMS3 influences the regulation of microRNA expression or stabilization. The absence of RBMS3 activates the Wnt/ß-catenin pathway. The expression of c-Myc, another target of the Wnt/ß-catenin pathway, is correlated with the RBMS3 expression. Numerous studies have focused solely on the interaction of RBMS3 with the epithelial-mesenchymal transition (EMT) protein machinery. EMT plays a vital role in cancer progression, in which RBMS3 is a new potential regulator. It is also significant that RBMS3 may act as a prognostic factor of overall survival (OS) in different types of cancer. This review presents the current state of knowledge about the role of RBMS3 in physiological and pathological processes, with particular emphasis on carcinogenesis. The molecular mechanisms underlying the role of RBMS3 are not fully understood; hence, a broader explanation and understanding is still needed.

Influence of Single Experience with Intraoperative Near-Infrared Autofluorescence on Postoperative Parathyroid Insufficiency after Thyroidectomy - A Preliminary Clinical Study.

Introduction: Total thyroidectomy has become the most common thyroid procedure. This treatment method results in most postoperative hypocalcemia (PH) and hypoparathyroidism (HPT) cases due to the unwitting removal of the parathyroid glands (PTGs). Near-infrared autofluorescence (NIRAF) is a new method that helps identify PTGs. This study aimed to determine whether short-term experience with intraoperative NIRAF may influence postoperative complications after thyroidectomy. Materials and methods: Overall, 65 patients who underwent thyroidectomy by one high-volume surgeon were enrolled in the study between March 2018 and August 2021. In August 2020, the surgeon performed four operations using the NIRAF device. After that experience, the technique of operating and preserving PTGs has been totally changed. Postoperative serum calcium (Ca) and parathormone (PTH) concentrations were measured. Using retrospective study analysis, we assessed the rate of PH and HPT. Results: There was no statistically significant difference in Ca (p = 0.1612) and PTH (p = 0.3590) concentrations between groups operated on before and after the NIRAF experience. The serum concentrations of Ca and PTH of all patients were positively correlated (r = 0.4074; p = 0.0022) as well as the Ca concentration and age of patients (r = 0.3292; p = 0.0116), respectively. Conclusions: These findings suggest that short-term NIRAF experience, and changing attitude to preserving PTGs does not affect thyroidectomy outcomes, even when utilized by a highly experienced high-volume thyroid surgeon. However, continuous use of NIRAF might enhance treatment outcomes, particularly for surgeons with limited experience.

Expression of NUCB2/NESF-1 in Breast Cancer Cells.

Recently, the expression of NUCB2/NESF-1 has been linked to tumor development. We report NUCB2/NESF-1 expression and its relation to clinicopathological parameters in breast cancer cells. Immunohistochemical reactions were conducted on 446 cases of invasive ductal carcinoma (IDC) and 36 cases of mastopathy. The expression of NUCB2/NESF-1 was also examined at the mRNA and protein levels in breast cancer cell lines. A statistically significant higher level of NUCB2/NESF-1 in IDC cells was noted compared to that in mastopathy samples. The level of NUCB2 expression in the cytoplasm of IDC cells decreased with the increasing degree of tumor malignancy (G). Higher NUCB2 expression was found in tumors with estrogen receptor (ER)-positive and progesterone receptor (PR)-positive phenotypes compared to that in estrogen-receptor-negative and progesterone-receptor-negative cases. Moreover, a higher expression was shown in ER(+) and PR(+) MCF-7 and T47D cell lines compared to that in triple-negative MDA-MB-468 and normal human breast epithelial cells. The analysis of the five-year survival rate indicated that a positive NUCB2/NESF-1 expression in tumor cells was also associated with longer patient survival. The study results suggest that NUCB2/NESF1 may play an important role in malignant transformation and may be a positive prognostic factor in IDC.

Expression of Zyxin in Non-Small Cell Lung Cancer-A Preliminary Study.

BACKGROUND: The potential involvement of zyxin (ZYX) in carcinogenesis has been investigated in many cancer types. However, there are a limited number of studies on the role of ZYX in the progression of non-small cell lung cancer (NSCLC). Since lung cancer is one of the most frequently diagnosed carcinomas, the aim of our study was to determine the localization and expression levels of ZYX in NSCLC and to correlate the results with the clinicopathological data. MATERIALS AND METHODS: The expression of ZYX was assessed in NSCLC cases and in cell lines representing this tumor type. Levels of ZYX were determined in the clinical material using immunohistochemistry (IHC) and Western Blot. Real-time PCR was used to assess ZYX mRNA levels. The expression of ZYX was also checked in NSCLC cell lines using real-time PCR, Western Blot, and immunofluorescence/immunocytochemistry. RESULTS: The results showed lower levels of ZYX in NSCLC cells compared with control tissues. This trend was observed at the protein and mRNA levels. The assays on the NSCLC model also demonstrated lower levels of ZYX in cancer cells compared with control cells. CONCLUSIONS: The decreased expression of ZYX in NSCLC may indicate a suppressor role of this protein in NSCLC.

Myokines in Acromegaly: An Altered Irisin Profile.

Introduction: The muscle is an endocrine organ controlling metabolic homeostasis. Irisin and myostatin are key myokines mediating this process. Acromegaly is a chronic disease with a wide spectrum of complications, including metabolic disturbances. Purpose: To examine the influence of acromegaly on irisin and myostatin secretion and their contribution to metabolic profile and body composition. Materials and Methods: In 43 patients with acromegaly and 60 controls, serum levels of irisin, myostatin, growth hormone (GH), insulin-like growth factor 1 (IGF-1), parameters of glucose, and lipid metabolism were determined. Body composition was assessed with dual-energy x-ray absorptiometry. Results: The irisin concentration was significantly lower in patients with acromegaly compared to controls (3.91 vs. 5.09 µg/ml, p = 0.006). There were no correlations between irisin and GH/IGF-1 levels. In the study group, irisin was negatively correlated with fasting insulin (r = -0.367; p = 0.042), HOMA-IR (r = -0.510; p = 0.011), and atherogenic factors: Castelli I (r = -0.416; p = 0.005), Castelli II (r = -0.400; p = 0.001), and atherogenic coefficient (AC) (r = -0.417; p = 0.05). Irisin and myostatin concentrations were also lower in acromegalics with insulin resistance than without (2.80 vs. 4.18 µg/ml, p = 0.047; 81.46 vs. 429.58 ng/L, p = 0.018, respectively). There were no differences between study group and controls in myostatin concentration. Myostatin levels negatively correlated with GH (r = -0.306; p = 0.049), HOMA-IR (r = -0.046; p = 0.411), and insulin levels (r = -0.429; p = 0.016). Conclusions: Decreased irisin concentrations in acromegaly may suggest impaired hormonal muscle function contributing to metabolic complications in this disorder. However, learning more about the association between myostatin and GH in acromegaly requires further studies. Nevertheless, it appears that myostatin is not critical for muscle mass regulation in acromegaly.

The frequency of TLR2 (rs3804099, rs3804100, and rs5743708) and TLR4 (rs4986790 and rs4986791) polymorphisms in women with polycystic ovary syndrome - preliminary study.

INTRODUCTION: Low-grade chronic inflammation may participate in PCOS etiology. Toll-like receptors (TLRs) may play a pivotal role in the initiation and progression of inflammatory process. We examined TLR2 and TLR4 gene polymorphisms in women with PCOS and their associations with metabolic/hormonal parameters. MATERIAL AND METHODS: Sixty-eight women qualified for the study. PCOS was diagnosed in 40 women. The control group consisted of 28 women. All patients underwent anamnesis, physical examination, anthropometric measurements, and biochemical/hormonal assessments. The TLRs gene polymorphism was tested using PCR and the minisequencing method. RESULTS: The frequency of TLR2 gene polymorphisms genotypes (rs3804099, rs3804100, and rs5743708) did not differ significantly between the groups. The difference in frequency of genotypes of TLR4 gene polymorphisms (rs4986790 and rs4986791) was close to the statistical significance level. No significant correlations between TLR2/TLR4 polymorphisms and anthropometric/metabolic parameters in PCOS group were observed. However, the relationship between HDL concentration and TLR2 S450S (rs3804100) polymorphism was close to the statistical significance level. Positive correlations between the two TLR4 polymorphisms (rs4986790 and rs4986791) were found, as well as between the TLR2 S450S (rs3804100) gene polymorphism and FSH concentration. CONCLUSIONS: The TLR4 gene polymorphism may play a role in the PCOS etiopathogenesis but this observation needs further investigation.

Metallothioneins in Inflammatory Bowel Diseases: Importance in Pathogenesis and Potential Therapy Target.

Immunological disorders, increased oxidative stress, and damage to the epithelial barrier play an important role in the pathogenesis of inflammatory bowel diseases (IBDs). In the treatment of patients with Crohn's disease (CD) and ulcerative colitis (UC), it is increasingly common to use biological drugs that selectively affect individual components of the inflammatory cascade. However, administering the medicines currently available does not always result in obtaining and maintaining remission, and it may also lead to the development of resistance to a given agent over time. Metallothioneins (MTs) belong to the group of low molecular weight proteins, which, among others, regulate the inflammation and homeostasis of heavy metals as well as participating in the regulation of the intensity of oxidative stress. The results of the studies conducted so far do not clearly indicate the role of MTs in the process of inflammation in patients with IBD. However, there are reports that suggest the possibility of using MTs as a potential target in the treatment of this group of patients.

Role of tesmin expression in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is the most commonly diagnosed cancer and the most frequent cause of cancer-associated mortality worldwide. Tesmin (MTL5) is a 60 kDa protein which has cysteine rich motifs, characteristic of metallothioneins. Tesmin expression was first observed in germ cells during spermatogenesis. Increased tesmin expression in NSCLC has been described previously. Minichromosome maintenance proteins (MCMs) serve a critical role in replication and cell cycle progression, i.e. in NSCLC. The aim of the present study was to evaluate the localization and intensity of tesmin, MCM5 and MCM7 protein expression in NSCLC and their association with the clinicopathological data of patients. Archival paraffin blocks of 243 cases of NSCLC and 104 non-cancerous tissue samples from the surgical margin (control) were obtained from patients treated at the Clinic of Thoracic Surgery of Wroclaw Medical University (Wroclaw, Poland) between 2010 and 2016, and were used for tissue microarrays and immunohistochemical (IHC) experiments. Laser capture microdissection was used for the isolation of cancer cells from 36 frozen samples of NSCLC and 8 control samples, and subsequently, MTL5, MCM5 and MCM7 mRNA expression was detected separately by reverse transcription-quantitative PCR. Positive cytoplasmic and nuclear tesmin, as well as nuclear MCM5 and MCM7 IHC expression were observed in 95.1, 83.67, 95.51 and 100% of the NSCLC cases, respectively. MTL5, MCM5 and MCM7 mRNA expression was observed in 91.66% of the cancer cases for all genes. The statistical analysis revealed increased tesmin IHC expression in cancer cells compared with the control. A positive correlation was observed between the IHC expression of nuclear tesmin and MCM5 proteins (r=0.33; P<0.0001) and nuclear tesmin and MCM7 proteins (r=0.315; P<0.0001). In addition, a positive correlation between the mRNA expression levels of MTL5 and MCM5 (r=0.421; P<0.05), MTL5 and MCM7 (r=0.557; P<0.01) was demonstrated. The survival analysis revealed that the presence of IHC cytoplasmic tesmin expression was a positive prognostic marker in NSCLC (P=0.0524). Furthermore, in vitro experiments performed on the NCI-H1703 cell line revealed that silencing of MTL5 mRNA and tesmin caused the downregulation of the expression levels of MCM5 and MCM7 and decreased the number of cells in the G2 phase. A positive association among tesmin, MCM5 and MCM7 could indicate a possible role of tesmin in the proliferation of NSCLC cancer cells.

Etiology, baseline clinical profile and comorbidities of patients with Cushing's syndrome at a single endocrinological center.

PURPOSE: The aim of this study was to compare phenotype of patients with pituitary, adrenal and ectopic CS and identify the differences regarding biochemical parameters, clinical presentations, and comorbidities in CS patients who were diagnosed at the single endocrinological center in Wroclaw. METHODS: The study population involved 64 patients with CS (53 women and 11 men) diagnosed in Department of Endocrinology, Diabetes and Isotope Therapy in 2000-2018. Patients were divided into three etiologic groups: pituitary dependent-CS (P-CS) (64%), adrenal dependent CS (A-CS) (25%), and CS from an ectopic source (E-CS) (11%). RESULTS: Percentage of men in the A-CS group was significantly higher than in the other etiologic groups. ACTH, UFC, and cortisol in DST were significantly higher in E-CS group compare to P-CS and A-CS (p < 0.05). Mean potassium level in E-CS group was significantly lower than in P-CS and A-CS (p < 0.05). Median of time elapsed to diagnosis was significantly lower in the E-CS group compared with either the P-CS and the A-CS group (p < 0.01). The most frequently symptoms in CS patients were skin alterations (82.8%), weight gain (81.2%), and hypertension (81.2%). CONCLUSIONS: The epidemiology of CS is changing toward a growing proportion of A-CS. All patients with E-CS presented a profound hypokalemia. Salient hypokalemia could be a biochemical marker more suggestive for E-CS rather than P-CS. The incidence of diabetes is more frequent in E-CS group than in P-CS and A-CS groups.

Prognostic Significance of Stromal Periostin Expression in Non-Small Cell Lung Cancer.

BACKGROUND: The microenvironment of solid tumours is significant in cancer development and progression. The aim of this study was to determine periostin (POSTN) expression by cancer-associated fibroblasts (CAFs) in non-small-cell lung cancer (NSCLC), as well as to assess associations with clinicopathological factors and prognosis. MATERIALS AND METHODS: Immunohistochemical analysis of POSTN expression was performed on NSCLC (N = 700) and non-malignant lung tissue (NMLT) (N = 110) using tissue microarrays. Laser capture microdissection (LCM) for isolation of stromal and cancer cells of NSCLC was employed, and subsequently, POSTN mRNA expression was detected by real-time PCR. Immunofluorescence reaction and colocalisation analysis were performed by confocal microscopy. RESULTS: Expression of POSTN in CAFs was significantly higher in NSCLC and in the adenocarcinoma (AC) and squamous cell carcinoma (SCC) subtypes compared to NMLT. POSTN expression in CAFs increased with clinical cancer stage, grades (G) of malignancy, and lymph node involvement in NSCLC. Higher POSTN expression in CAFs was an independent prognostic factor for overall survival (OS). LCM confirmed significantly higher POSTN mRNA expression in the stromal cells (CAFs) compared to the lung cancer cells. CONCLUSIONS: POSTN produced by CAFs might be crucial for NSCLC progression and can be an independent negative prognostic factor in NSCLC.

Effect of Physical Training on the Levels of Sex Hormones and the Expression of Their Receptors in Rats With Induced Mammary Cancer in Secondary Prevention Model - Preliminary Study.

BACKGROUND/AIM: Breast cancer is the most common malignant tumor among women worldwide. In previous work, we presented results of physical activity in primary prevention in a model of induced mammary gland cancer. In the present study, we assessed the influence of physical activity on sex hormone levels (estradiol and progesterone) and the expression of their receptors (ER, PR), as well as the level of apoptosis of tumor cells in secondary prevention. MATERIALS AND METHODS: Fifty 1-month-old female Sprague-Dawley rats received intraperitoneal injection of 180 mg/kg body weight of N-methyl-N-nitrosourea (MNU) for tumor induction. Three months after the administration of MNU, rats were divided into four groups: low-intensity, moderate-intensity, and high-intensity physical training groups (combined as PT) and a sedentary control (SC) group. Physical training was conducted 5 days per week with a three-position treadmill according to a precisely described protocol. The entire training was completed by 32 rats from which tissue and blood were collected for further analysis. Immunohistochemistry for ER and PR expression, terminal deoxynucleotidyl transferase dUTP nick-end labeling method for detection of apoptosis, and enzyme-linked fluorescent assay for detection of plasma hormone levels (estradiol and progesterone) were performed. Statistical analysis used p<0.05 as the significance level. RESULTS: Significantly stronger expression of ER and PR was found in the SC in comparison to the PT group (p=0.035 and p=0.036, respectively). No statistically significant differences were found in estradiol or progesterone concentrations between SC and PT groups. Apoptosis was non-significantly increased in the PT group in comparison with the SC group. Stronger apoptosis in the PT group correlated positively with the level of training intensity (r=0.35, p=0.05). CONCLUSION: Physical training may reduce ER and PR expression in breast cancer cells, and reduce cell sensitivity to pro-proliferative and anti-apoptotic effects of estrogens, ultimately leading to apoptosis.