ABSTRACT
Some NK cell subpopulations may be involved in the modulation of fibrogenesis in the liver. The aim of the study was to evaluate the relationship between the number and phenotype of NK cell subsets in peripheral blood (PB) and total NK cell percentage, population density and the degree of liver fibrosis of patients infected with hepatitis C virus (HCV+). The study group consisted of 56 HCV+ patients, divided into two subgroups: patients with mild or moderate fibrosis and patients with advanced liver fibrosis or cirrhosis (F ≥ 3 in METAVIR classification). The preparations were stained with H-E and AZAN staining. NK cells were targeted with anti-CD56 antibody and identified automatically in situ using the DakoVision system. Assessment of different NK cell subsets in PB was performed with the flow cytometry technique. In the PB of HCV+ patients with advanced liver fibrosis, there was a lower proportion of CD62L+; CD62L+/CD94++; CD27+; CD127+/CD27+ and CXCR3+/CD27+ NK subsets, as compared to patients with mild/moderate liver fibrosis. The results also showed no association between total PB NK cell level and total intrahepatic NK cell population density between patients with mild/moderate fibrosis and with advanced liver fibrosis. However, positive correlations between the PB levels of CD94+ and CD62L+ NK cell subsets and the intrahepatic total NK cell percentage and population density in the liver, irrespectively to the extent of fibrosis, were observed. Additionally, positive correlation was found between the PB CXCR3+/CD94+ NK cell percentages and intrahepatic NK cell percentages in patients with advanced hepatic fibrosis. Lower blood availability of specific NK subsets in patients with chronic type C hepatitis might be a cause of progression of liver fibrosis via insufficient control over hepatic stellate cells.
ABSTRACT
We studied the long-term effect of ileal transposition (IT) metabolic surgery on the hepatokines: retinol-binding protein-4 (RBP4), α-2-HS-glycoprotein (aHSG/fetuin-A), and fibroblast growth factor 21 (FGF21), C-reactive protein (CRP) plasma levels, glucose metabolism, body weight, liver histology, as well as total lipids concentration in muscle, liver, and fat tissue of obese Zucker (Crl:ZUC(ORL)-Leprfa) rats. 14 adult males were randomly submitted either to IT or SHAM (control) surgery. Pre-operative hepatokines plasma levels were not significantly different in rats submitted to IT or SHAM protocol. Three months after the procedures the plasma levels of RBP4, aHSG, FGF21, and CRP were significantly lower in IT-operated animals when compared to SHAM-operated group. Three and 12 weeks after the IT and SHAM surgery, the AUCOGTT were significantly lower than AUCOGTT before the surgery. HOMA-IR was lower in rats after IT surgery in comparison to the SHAM-operated rats. Muscle and liver total lipids concentration was reduced after the IT procedure when compared to pre-IT conditions. IT had a significant reductive impact on the body weight in comparison to SHAM surgery in the 4th, 6th, 8th, and 10th week after the surgery. We conclude that IT reduces hepatokines' plasma concentrations, muscle and liver total lipids concentration but not the inflammatory processes in the liver of Zucker (Crl:ZUC(ORL)-Leprfa) rats.
Subject(s)
Bariatric Surgery/methods , Cytokines/blood , Glucose/metabolism , Lipid Metabolism , Obesity/surgery , Animals , Male , Rats , Rats, ZuckerABSTRACT
Water-soluble polymer-drug conjugates were obtained and analyzed towards their potential use as prodrugs for two hydrophobic antipsoriatic agents, including methotrexate (MTX) and acitretin (AC). The conjugation efficacy of MTX decreased with a decreasing molar ratio of N,N-dimethylaminoethyl methacrylate (DMAEMA) repeating units in the polymethacrylic chains. Cytotoxicity of positively charged (from +5 to +10 mV) nano- and microparticles (3-1500 nm in DMEM at 37 °C) were estimated by in vitro MTT and Annexin-V apoptosis assays on Me45, NHDF, HaCaT and BEAS-2B cell lines. Further, cell cycle analysis revealed arrest in G0/G1 phase in melanoma cells, while neither apoptosis induction nor cell cycle arrest occurred in normal epidermal and epithelial cells. Tested conjugates displayed a novel cytostatic effect in Me45 cells and a pro-apoptotic effect in HaCaT cells. Epithelial BEAS-2B cells were the most sensitive to the tested conjugates and responded via induction of necrosis. Cell line models allowed for characterization of the biologically relevant potential action of pro-drugs. Additionally, a skin in vitro evaluation assay provided the first known evidence of side-effect reduction with pro-drug use. Histological examinations confirmed the lack of negative effects of conjugates on the skin and showed no irritating properties.
Subject(s)
Acitretin/chemistry , Methotrexate/chemistry , Polymethacrylic Acids/chemical synthesis , Polymethacrylic Acids/toxicity , Psoriasis/drug therapy , Apoptosis/drug effects , Cell Cycle/drug effects , Cell Line, Tumor , Chemistry Techniques, Synthetic , Dose-Response Relationship, Drug , Humans , Polymethacrylic Acids/chemistry , Polymethacrylic Acids/therapeutic use , Skin/drug effectsABSTRACT
AIM OF THE STUDY: Chronic hepatitis C (CHC) is a viral disease with metabolic disturbances involved in its pathogenesis. Adipokines may influence the inflammatory response and contribute to development of metabolic abnormalities in CHC. Visfatin exerts immunomodulatory and insulin-mimetic effects. The aim was to measure visfatin serum concentrations and its mRNA hepatic expression in non-obese CHC patients and to assess the relationships with metabolic and histological parameters. MATERIAL AND METHODS: In a group of 63 non-obese CHC patients (29 M/34 F) infected with genotype 1b aged 46.6 ±14.6 years, body mass index (BMI) 24.8 ±3.0 kg/m2, serum visfatin levels and its mRNA hepatic expression were examined and the subsequent associations with metabolic and histopathological features were assessed. RESULTS: Serum visfatin levels were significantly higher in CHC patients compared to controls (22.7 ±5.7 vs. 17.8 ±1.5 ng/ml, p < 0.001). There was no difference in serum visfatin and its mRNA hepatic expression regardless of sex, BMI, insulin sensitivity and lipids concentrations. There was no mutual correlation between serum visfatin and visfatin mRNA hepatic expression. Hepatic visfatin mRNA levels but not visfatin serum levels were higher in patients with steatosis (1.35 ±0.75 vs. 0.98 ±0.34, p = 0.009). CONCLUSIONS: Serum visfatin levels may reflect its involvement in chronic inflammatory processes accompanying HCV infection. Increased visfatin mRNA hepatic expression in patients with steatosis seems to be a compensatory mechanism enabling hepatocytes to survive metabolic abnormalities resulting from virus-related lipid droplet deposition prerequisite to HCV replication.
ABSTRACT
The study evaluates the influence of steatosis on hepatocytes proliferative potential, reflected by proliferating cell nuclear antigen (PCNA) expression in chronic hepatitis C (CHC) patients both in steatotic and non-steatotic areas of lobules. The liver histology was evaluated according to Kleiner's score. Nonalcoholic steatohepatitis (NASH) was also defined as the presence of lobular inflammation, hepatocyte ballooning and steatosis. Expression of PCNA was significantly in patients with definite NASH compared to those with simple steatosis, but not to those with borderline NASH. Advanced steatosis negatively influenced PCNA expression. NASH not only affects PCNA expression in staetotic, but also in non-steatotic lobule areas. Expression of PCNA could be an independent indicator of changes in hepatocyte metabolism in CHC patients. High NAS values and low PCNA expression may be a negative prognostic factor in predicting the further course of the disease.
Subject(s)
Hepatitis C, Chronic/pathology , Hepatocytes/cytology , Non-alcoholic Fatty Liver Disease/pathology , Cell Proliferation , Humans , Inflammation , LiverABSTRACT
BACKGROUND: The proper use of new medical tests in clinical practice requires the establishment of their value and range of diagnostic usefulness. While whole-exome sequencing (WES) has already entered the medical practice, recognizing its diagnostic usefulness in multifactorial diseases has not yet been achieved. AIMS: The objective of this study was to establish usability of WES in determining genetic background of chronic cholestatic liver disease (CLD) in young patients. METHODS: WES was performed on six young patients (between 17 and 22 years old) with advanced fibrosis or cirrhosis due to CLD and their immediate families. Sequencing was performed on an Ion Proton sequencer. RESULTS: On average, 19,673 variants were identified, of which from 7 to 14 variants of an individual were nonsynonymous, homozygous, recessively inherited, and considered in silico as pathogenic. Although monogenic cause of CLD has not been determined, several heterozygous rare variants and polymorphisms were uncovered in genes previously known to be associated with CLD, including ATP8B1, ABCB11, RXRA, and ABCC4, indicative of multifactorial genetic background. CONCLUSIONS: WES is a potentially useful diagnostic tool in determining genetic background of multifactorial diseases, but its main limitation results from the lack of opportunities for direct linkage between the uncovered genetic variants and molecular mechanisms of disease.
ABSTRACT
Angiogenesis can be described as a formation of new vessels from the existing microvasculature and is a process of great importance to the tumor development. Parathyroid tissue can trigger spontaneous induction of angiogenesis in vitro and in vivo models in a vascular endothelial growth factor (VEGF)-dependent manner. Autotransplantated parathyroid tissue after thyroidectomy is able to form new vasculature and produce parathormone, maintaining calcium homeostasis. A great amount of factors contributes to the process of new vessel formation in primary hyperparathyroidism, such as VEGF, transforming growth factor ß, and angiopoietins. Studies demonstrated that markers for angiogenesis can be useful in distinguishing between parathyroid hyperplasia and neoplasia, due to the increased angiogenesis in parathyroid proliferative lesions compared with parathyroid adenomas. These factors include, inter alia, VEGF, VEGFR2, CD105, and fibroblast growth factor-2. Although these differences appear promising in the differential diagnosis, there is an overlap between benign and malignant parathyroid lesions and there is no definite cutoff value. Loss of heterozygosity and comparative genomic hybridization studies revealed chromosomal regions frequently altered in parathyroid tumorigenesis at 9p21, 1p21-22, 1p35-36, and 11q13. Therefore, immunohistochemistry and genetic testing should be an additional diagnostic marker in combination with the traditional criteria. A better understanding of angiogenesis in primary hyperparathyroidism could result in more precise assessment of diagnosis and more effective treatment, especially in those cases, in which the commonly used parameters are insufficient.
Subject(s)
Hyperparathyroidism, Primary/pathology , Parathyroid Glands/blood supply , Parathyroid Glands/pathology , Humans , Hyperparathyroidism, Primary/physiopathology , Neovascularization, Pathologic/pathology , Parathyroid Neoplasms/blood supply , Parathyroid Neoplasms/pathologyABSTRACT
Antioxidant enzymes (AOEs), including superoxide dismutase isoenzymes (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) along with glutathione reductase (GR), reduced glutathione (GSH) and glutathione transferase (GST), are thought to be necessary for life process in all oxygen-metabolizing cells by removing reactive oxygen species (ROS). The biological significance of AOEs in transformed cells is still unclear, but their capacity to survive may be affected by changes in cellular process such as proliferation, invasiveness, migration, apoptosis and drug resistance. This review summaries the significance of antioxidant enzymes in cancer cell progression mainly in an in vitro context.
Subject(s)
Antioxidants/metabolism , Neoplasms/enzymology , Oxidative Stress/physiology , Reactive Oxygen Species/metabolism , Animals , Disease Progression , Glutathione Peroxidase/metabolism , Glutathione Transferase/metabolism , Humans , Superoxide Dismutase/metabolismABSTRACT
INTRODUCTION: Chemerin seems to be involved in pathogenesis of chronic hepatitis C (CHC). Hepatic expressions of chemerin and its receptor, chemokine receptor-like 1 (CMKLR1), in CHC have not been studied so far. AIM: To evaluate chemerin and CMKLR1 hepatic expression together with serum chemerin concentration in CHC patients and to assess their relationship with metabolic and histopathological abnormalities. METHODS: The study included 63 nonobese CHC patients. Transcription of chemerin and CMKLR1 was assessed by quantitative real-time PCR, while serum chemerin was assessed by enzyme-linked immunosorbent assay. RESULTS: Expression of chemerin and CMKLR1 was present in the liver of all CHC patients regardless of sex or age. This expression was not associated with necroinflammatory activity and steatosis grade, fibrosis stage, and metabolic abnormalities. There was a negative association between serum chemerin and chemerin hepatic expression (r = (-0.41), P = 0.006). CONCLUSION: The study for the first time confirmed a marked expression of chemerin and CMKLR1 in the liver of CHC patients. The study was performed using the homogenates of human liver tissue, so it is not possible to define whether hepatocytes or other cell types which are abundantly represented in the liver constitute the main source of chemerin and CMKLR1 mRNA.
Subject(s)
Chemokines/metabolism , Hepatitis C, Chronic/metabolism , Intercellular Signaling Peptides and Proteins/metabolism , Liver/metabolism , Receptors, Chemokine/metabolism , Body Mass Index , Case-Control Studies , Chemokines/blood , Female , Gene Expression Regulation , Hepatitis C, Chronic/blood , Hepatitis C, Chronic/genetics , Hepatocytes/metabolism , Hepatocytes/pathology , Humans , Intercellular Signaling Peptides and Proteins/blood , Logistic Models , Male , Middle AgedABSTRACT
Inflammatory bowel disease (IBD) is characterized by a chronic inflammation accompanied by procoagulation settings. However, tissue hemostasis in IBD patients was only incidentally reported. Accordingly, the current study characterizes changes in tissue hemostasis components in a colon inflammatory setting. Serial cryostat sections of endoscopic mucosal biopsy specimens taken from 26 consecutive IBD patients diagnosed de novo and normal colon resection specimens taken from 6 patients were immunohistochemically stained with monoclonal anti-human tissue factor (TF), tissue factor pathway inhibitor (TFPI), thrombomodulin (TM), as well as CD3 and CD68 positive cells. The hemostatic components studied differed significantly from the control subjects. Up-regulation predominated in the case of TF while down-regulation was mainly found in TM and TFPI in IBD. In the control sections, TF was observed in a few fibroblast-shaped cells in the lamina propria, while in the majority of IBD sections, TF positively stained small microvessels, infiltrating mononuclear cells and fibroblast-shaped cells tightly surrounding the colon crypts. Thrombomodulin intensively stained the endothelium of the small capillary vessels in the control, whereas such staining mainly accompanied infiltrating mononuclear cells of the IBD subjects. Tissue factor pathway inhibitor positively stained the endothelium of the small capillary vessels in the control group, whereas in the IBD group endothelial cells presented only weak TFPI staining. The mean number of CD3-positive lymphocytes in IBD was 23.3 ± 14.3, but the mean number of CD68-positive cells was 114.5 ± 55.8. In the control sections, it was 4.1 ± 2.4 and 39.6 ± 17.9, respectively. There was no relationship between CD3 and CD68 (+) cells and the hemostasis markers studied. The results of the current study indicate a shift of tissue hemostasis toward the procoagulant state irrespective of the severity of inflammatory infiltration. In addition, TF distribution in the colon sections of IBD patients may indicate a role in the restoration of the barrier function in injured intestinal mucosa.
Subject(s)
Colitis, Ulcerative/blood , Hemostasis , Antigens, CD/metabolism , Biomarkers/blood , Biopsy , Colon/metabolism , Endoscopy , Endothelium, Vascular/metabolism , Female , Gene Expression Regulation , Humans , Lipoproteins/metabolism , Male , Middle Aged , Thrombomodulin/metabolism , Thromboplastin/metabolismABSTRACT
INTRODUCTION: Fibroblast growth factor-21 (FGF21) regulates glucose, lipid, and energy homeostasis. Retinol-binding protein-4 (RBP4) controls metabolic and proliferative cell functions. AIMS AND METHODS: Aims of the study were to assess (1) serum FGF21 and RBP4 levels in 75 non-obese chronic hepatitis C (CHC) patients and 41 healthy controls similar in age and BMI; (2) the relationship between their serum concentration and insulin resistance, liver histology, and biochemical parameters; (3) their effectiveness as diagnostic markers. RESULTS: FGF21 levels increased significantly in CHC patients compared with controls (p = 0.04). CHC patients with steatosis had significantly higher FGF21 levels compared with those without steatosis (p = 0.01). FGF21 concentration was positively related to steatosis grade (r = 0.39, p = 0.007). RBP4 levels did not differ between CHC patients and controls, but were negatively associated with necro-inflammatory activity grade (r = (-0.34), p = 0.04), with significantly higher levels in patients with minimal inflammatory activity (G1 vs. G2/3, p < 0.001; G1 vs. G2, p = 0 < 001; G1 vs. G3, p = 0.01). After stepwise linear regression analysis adjusting for potential confounders, RBP4 levels retained their independent significance as a predictor of necro-inflammatory activity (ß = -0.31; t = -2.15, p = 0.035) and FGF21 levels as a predictor of steatosis (ß = 0.34; t = 2.31, p = 0.024). Serum FGF21 correlated with serum RBP4 levels (r = 0.32, p = 0.02). CONCLUSIONS: Serum FGF21 levels increased in CHC patients, especially in those with steatosis and were associated with steatosis grade. FGF21 seems to be a useful diagnostic marker in determining hepatic steatosis in CHC. A negative association between serum RBP4 and necro-inflammatory activity indicates that disease severity may determine RBP4 levels.
Subject(s)
Fatty Liver/blood , Fatty Liver/pathology , Fibroblast Growth Factors/blood , Hepatitis C, Chronic/blood , Hepatitis C, Chronic/pathology , Retinol-Binding Proteins, Plasma/metabolism , Adult , Alanine Transaminase/blood , Biomarkers/blood , Body Mass Index , Case-Control Studies , Fatty Liver/complications , Female , Hepatitis C, Chronic/complications , Humans , Insulin Resistance , Linear Models , Male , Middle Aged , Multivariate Analysis , Statistics, NonparametricABSTRACT
A 72 year-old woman with primary hyperparathyroidism was operated for parathyroid crisis. PTH serum level was 808 pg/mL. During the operation, only two superior parathyroid glands were found. One was normal, and hypertrophy was revealed in the other. After the surgical procedure, PTH serum level was 726.5 pg/mL. Helical computer tomography examination showed a heterogeneous mass in the anterior mediastinum. The tumour was removed via a sternotomy approach. Histopathological examination revealed parathyroid carcinoma. PTH level dropped to 5.74 pg/mL. Cytofluorometric examination revealed diploidy (DI = 1) in both the hypertrophic and the unchanged upper glands, whereas parathyroid cancer was aneuploid. After the initial operation, the woman was discharged from the hospital on the 27th postoperative day. One year after surgical procedures, she is well. She has to take calcium.
Subject(s)
Calcium/administration & dosage , Carcinoma/surgery , Hyperparathyroidism, Primary/surgery , Parathyroid Hormone/metabolism , Parathyroid Neoplasms/surgery , Aged , Aneuploidy , Carcinoma/complications , Carcinoma/genetics , Diploidy , Female , Follow-Up Studies , Humans , Hyperparathyroidism, Primary/complications , Hyperparathyroidism, Primary/genetics , Parathyroid Neoplasms/complications , Parathyroid Neoplasms/genetics , Treatment OutcomeABSTRACT
Vaspin was found to modulate insulin resistance (IR) and to inhibit proinflammatory and profibrogenic agents. The aim of the study was to evaluate vaspin serum concentration prior to and after antiviral treatment and to assess its relationship with morphological alterations, IR and response to antiviral therapy. The study encompassed 75 non-obese, non-diabetic chronic hepatitis C (CHC) patients, 30 of whom underwent antiviral treatment. Serum vaspin levels decreased in CHC patients and was positively associated with fibrosis stage (r = 0.44, p = 0.001). Serum vaspin was significantly higher in patients with septal fibrosis/cirrhosis or periportal fibrosis compared to those with portal fibrosis or without fibrosis (F3-4 vs. F2 vs. F1 vs. F0, p = 0.012). A marked increase in the serum vaspin level occurred in patients with periportal or more advanced fibrosis (F0-1 vs. F2-4, p < 0.001). Serum vaspin levels were also positively related to steatosis grade (r = 0.32, p = 0.03). Antiviral therapy did not change serum vaspin levels, irrespective of its efficiency. Our study showed that the serum vaspin level is decreased in CHC patients with non-advanced fibrosis, but the virus seems to have no direct effect on this finding. Progressive fibrosis is associated with rise of the vaspin level and this adipokine may serve as a predictor of advanced liver fibrosis.
Subject(s)
Hepatitis C, Chronic/blood , Hepatitis C, Chronic/pathology , Serpins/blood , Adult , Antiviral Agents/therapeutic use , Biomarkers/blood , Enzyme-Linked Immunosorbent Assay , Female , Hepatitis C, Chronic/drug therapy , Humans , Liver Cirrhosis/pathology , Liver Cirrhosis/virology , Male , Middle Aged , Young AdultABSTRACT
It is unclear whether angiogenesis merely represents a homeostatic mechanism aimed at ensuring an adequate oxygen supply or one that exerts an additional pathogenic role leading to liver damage in chronic hepatitis. Chronic hepatitis C (CHC) patients present a proangiogenic profile of angiogenic markers. Adipokines not only regulate adipose tissue and glucose metabolism, but also influence inflammation, fibrogenic process and production of proangiogenic factors. On the basis of this evidence we aimed to assess the number of new blood vessels in lobules and portal tracts in the liver and evaluate the relationship between angiogenesis intensity and serum adipokine concentrations in CHC. Our study showed a positive association between serum vaspin and angiogenesis intensity in portal tracts and lobules in CHC patients (r = 0.41, p = 0.04; r = 0.46, p = 0.03; respectively). Serum visfatin was found to be negatively related to angiogenesis in portal tracts and lobules but only in females (r = -0.76, p = 0.03; r= -0.95, p < 0.001; respectively). In conclusion, the role of some adipokines in liver angiogenesis seems to be different in females than in males. Serum vaspin concentration seems to reflect intensity of liver angiogenesis in CHC. Further studies are necessary to better determine the role of adipokines in new blood vessel formation in CHC.
Subject(s)
Adipokines/blood , Hepatitis C, Chronic/pathology , Liver/pathology , Neovascularization, Pathologic/pathology , Obesity , Adiponectin/blood , Adult , Chemokines/blood , Cytokines/blood , Female , Hepatitis C, Chronic/blood , Hepatitis C, Chronic/physiopathology , Humans , Intercellular Signaling Peptides and Proteins , Leptin/blood , Liver/blood supply , Liver/virology , Male , Middle Aged , Neovascularization, Pathologic/blood , Nicotinamide Phosphoribosyltransferase/blood , Serpins/blood , Sex Factors , Young AdultABSTRACT
INTRODUCTION: Lichen sclerosus (LS) is a chronic skin and mucosa inflammatory disease. It affects mainly the female anogenital area especially in postmenopausal period. The main symptoms include pruritus, burning, pain, sometimes urinary problems, or difficulties in defecation. Usually, porcelain-white plaques are seen in the skin and mucosa. The etiology and pathogenesis of LS are still uncertain. There are some research studies on possible genetic predisposition, yet autoimmune, hormonal, or infectious factors are not excluded. The typical treatment of LS is mainly pharmacological, although the alternative treatment method used in LS is photodynamic therapy (PDT), which is noninvasive technique based on selective destruction of lesions. Our study is focused on molecule markers of vascularisation (CD34), nervous cell function (myelin basic protein [MBP]), keratinocyte function (CD44), and proliferation index (Ki67) in cases treated with photodynamic method. MATERIALS AND METHODS: A group of 100 patients treated in our department was included in the study. All 100 women had LS on the basis of clinical and histological criteria. All the subjects underwent PDT. In all cases, skin biopsies were taken before and after treatment, and samples were analyzed with CD34, CD44, MBP, and Ki67 antibodies using immunohistochemical staining. RESULTS: The study shows the high efficacy of PDT in LS treatment including beneficial changes to CD34, CD44, and MBP immunostained molecules. The Ki67 proliferation index did not change significantly. A significant increase of CD34 (microvessel density), MBP, and CD44 expression was confirmed in the histological images and in the partial or full remission of clinical objective and subjective symptoms. CONCLUSIONS: The PDT is a very effective therapeutic method in LS treatment.
Subject(s)
Antigens, CD34 , Hyaluronan Receptors , Ki-67 Antigen , Myelin Basic Protein , Photochemotherapy , Vulvar Lichen Sclerosus/therapy , Female , Humans , Immunohistochemistry , Middle Aged , Treatment Outcome , Vulvar Lichen Sclerosus/metabolismABSTRACT
The data on the association between angiogenesis and mast cell density in cervical tumors and pretumoral conditions are scanty. The aims of the study were as follows: (1) to assess microvessel density and mast cell density in cervical lesions as well as in normal cervix samples and (2) to study the correlation between these variables. A hundred and one cervical samples were submitted to histopathological evaluation. Four study groups were distinguished: normal cervix samples, low-grade squamous intraepithelial lesions, high-grade squamous intraepithelial lesions, and invasive squamous cell carcinomas. The immunohistochemistry was performed using anti-CD34, Anti-Human Mast Cell Tryptase, and Anti-Human Mast Cell Chymase antibodies. The microvessels and mast cells in the corresponding areas of tissue samples were counted by three observers using a multi-headed microscope. Microvessel density and density of mast cells that contain tryptase increased from normal samples through intraepithelial lesions to invasive carcinoma. The density of mast cells containing chymase was significantly higher in invasive carcinomas than in normal samples. In the entire study population, but not in the separated study groups, significant correlations between microvessel density and mast cell density were found. A specific mechanism of this interaction still needs to be evaluated.
Subject(s)
Carcinoma, Squamous Cell/pathology , Mast Cells/pathology , Neovascularization, Pathologic/pathology , Uterine Cervical Dysplasia/pathology , Uterine Cervical Neoplasms/pathology , Cell Count , Cervix Uteri/pathology , Female , Humans , Immunohistochemistry , Statistics, NonparametricABSTRACT
The skeletal system is the third most frequent (after lungs and liver) seat of metastases, and metastatic tumours are the most common bone malignancies. The diagnostic work-up of spinal metastases begins with the identification of the primary neoplastic site. Histological analysis confirms the final diagnosis. The work-up of bony metastases poses considerable difficulty and requires the collaboration of a number of specialists. Historical paraffin-embedded tissue samples were subjected to a routine procedure for the preparation of histology specimens. All specimens were independently reassessed by two diagnosticians. The samples of metastatic tumours of 57 patients whose primary tumour sites had not been identified were subjected to an immunohistochemical analysis based on monoclonal antibodies and assays for antigens associated with tumours most often producing bony metastases, i.e.:: PSA, thyreoglobulin, villin, cytokeratin 7, cytokeratin 8, cytokeratin 17, cytokeratin 18, cytokeratin 19, cytokeratin 20, CD 38, oestrogen and progesterone and Vimentin, LCA, HMB-45 and S-100. The monoclonal antibodies and assays were shown to be useful aids for the identification of the histology and location of the primary tumour in patients in whom routine histological assessments had failed to determine the histological type of tumour. In many cases, effective immunohistochemical work-up can contribute to halting the progression of the tumour by enabling qualification for appropriate surgical and oncological treatment.
Subject(s)
Antibodies, Monoclonal/analysis , Antigens, CD/analysis , Biomarkers, Tumor/analysis , Bone Neoplasms/pathology , Bone Neoplasms/secondary , Humans , Immunohistochemistry/methods , Poland , Retrospective Studies , Sensitivity and Specificity , Staining and Labeling/methodsABSTRACT
BACKGROUND: The relationship between steatosis and angiogenesis in chronic hepatitis C (CHC) is unclear. AIM AND METHODS: The aim was to explain whether liver steatosis presence and its extent are associated with the number of new-formed blood vessels in lobules and portal tracts in CHC. 72 CHC patients infected with viral genotype 1b, 35 of whom had steatosis were evaluated. Monoclonal antibody anti-CD34 was used to identify new-formed blood vessels. RESULTS: Patients with steatosis had a significantly more advanced stage of fibrosis (p = 0.002) and higher inflammatory activity grade (p = 0.062). CD34 expression in portal tracts (CD34pt), lobules and fibrous septa (CD34lfs) and total (CD34) were significantly higher in patients with steatosis (p = 0.034; p = 0.021; p = 0.023, respectively). CD34, CD34pt and CD34lfs differed significantly between patients with various steatosis grade (p = 0.006; p = 0.009; p = 0.013, respectively). CD34 and CD34pt differed significantly between each steatosis grade whereas CD34lfs between grade 1 and 3. Fibrosis stage and inflammatory grade were positively associated with steatosis extent (p = 0.015; p = 0.003, respectively). CONCLUSIONS: Our observations suggest that extensive steatosis of liver parenchyma in CHC patients is associated with formation of new blood vessels in lobules and portal tracts. Understanding the relationship between steatosis, fibrosis and angiogenesis is therefore of great importance for the introduction of new therapeutic approaches and in the evaluation of CHC progression.
Subject(s)
Blood Vessels/pathology , Fatty Liver/pathology , Hepatitis C, Chronic/pathology , Neovascularization, Pathologic/pathology , Adult , Antigens, CD34/metabolism , Biomarkers/metabolism , Blood Vessels/metabolism , Female , Humans , Immunohistochemistry , Liver/blood supply , Liver/pathology , Liver Cirrhosis/metabolism , Liver Cirrhosis/pathology , Male , Middle AgedABSTRACT
Data regarding the assessment of angiogenesis in liver tissue in chronic hepatitis C (CHC) are rare. The study was performed to explain the association between the histopathological features and the number of new blood vessels in lobules and portal tracts in CHC. The second aim of the study was to define the localization of sprouting and pattern of formation of new vessels by estimating CD 34 antigen expression in the liver. The study involved 74 patients with CHC, infected with viral genotype 1b before antiviral therapy. The number of new-formatted blood vessels was positively associated with fibrosis stage and inflammatory activity grade in the liver biopsy from CHC patients. The relationship was evident in the portal tract, fibrous septa and periportal zones of lobules. The results suggest that inflammatory hepatocyte injury may promote neo-angiogenesis.
Subject(s)
Hepatitis C, Chronic/pathology , Inflammation/pathology , Liver/pathology , Neovascularization, Pathologic/pathology , Adult , Antigens, CD34/metabolism , Female , Fibrosis , Hepatitis C, Chronic/physiopathology , Humans , Inflammation/physiopathology , Liver/metabolism , Liver/physiopathology , Male , Middle Aged , Neovascularization, Pathologic/physiopathology , Statistics, NonparametricABSTRACT
INTRODUCTION: The skeletal system is the third most frequent (after lungs and liver) seat of metastases, and metastatic tumours are the most common type of bone malignancies. The aim of the study was to evaluate the influence of the type of neoplasm and method of treatment on the survival of patients with malignant spinal tumours. MATERIALS AND METHODS: A retrospective analysis of 452 patients operated on between 2000 and 2004 in the Orthopaedic Surgery Hospital in Piekary Slaskie revealed a group of 203 patients whose histopathologic examination confirmed the presence of neoplastic foci in the spine. Data concerning the type of surgery and tumour location in 139 patients with the most frequent malignant spinal tumors were analyzed. The other information concerning subsequent treatment was analyzed in the Maria Sklodowska-Curie Oncology Centre and Institute in Gliwice. Patient deaths were verified in the Regional Administrative Office in Katowice. RESULTS: The most common types of neoplasms producing spinal metastases (in patients who underwent surgery) were: breast cancer, prostatic adenocarcinoma and kidney cancer. Multiple myeloma was the most frequent diagnosis among primary bone neoplasms. The survival of patients with multiple myeloma was statistically longer than the survival of patients with renal, breast and prostatic cancer metastases. It appears that, in the absence of contraindications, the best treatment for patients with spinal metastases is locally radical surgery combined with radiation therapy (a single teleradiotherapy session of 8 Gy). This treatment resulted in a statistically significant prolongation of life of the patients. CONCLUSIONS: The length of survival of patients with malignant spinal metastases is influenced by the type of neoplasm and locally radical surgery combined with palliative radiation therapy.