Expression of prostaglandin E2 prostanoid receptor EP2 and interleukin-1ß in laryngeal carcinoma - preliminary study.

AIM OF THE STUDY: Expression of EP2 protein, the prostaglandin E2 (PGE2) receptor, produced by tumour microenvironment inflammatory cells as well as tumour cells, may promote cellular proliferation and growth in an autocrine and paracrine fashion. The phenomenon involving these proteins is regulated by interleukin 1ß (IL-1ß). Many researchers indicate a connection of EP2 and IL-1ß in various types of neoplasms with higher tumour progression and poor prognosis. The aim of this study was to analyse the EP2 expression within laryngeal carcinoma tissue and IL-1ß levels in peripheral blood mononuclear cell supernatants and to find relationships between clinicomorphological features. MATERIAL AND METHODS: A group of 50 patients with verified squamous cell laryngeal carcinoma was analysed in this study. The pathological evaluation included pTNM depth of invasion according to tumour front grading criteria. Immunohistochemical analysis for membranous staining of EP2 in tumour tissues was used. The IL-1ß expression was determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: Increased EP2 expression in carcinoma cells was confirmed for more advanced tumours (pT3-pT4 vs. pT1-pT2, p < 0.0001 and pN1-3 vs. pN0, p = 0.02). Tumours with the highest aggressiveness identified by deeper invasion of submucosa or cartilage were characterised by the highest expression of EP2 (p < 0.0001). In laryngeal carcinomas characterised by a lower differentiation the highest EP2 expression in tumour cells was noted (p = 0.009). A positive relationship between IL-1ß expression and the presence of lymph node metastases was also confirmed (p = 0.04). CONCLUSIONS: The study indicates the potential effect of EP2 receptor and IL-1ß on tumour progression in laryngeal carcinoma.

[Analysis of HIF-1α and COX-2 expression in tumor stroma and correlation with the degree of neoplasm invasiveness in laryngeal cancer--preliminary study]. / Analiza ekspresji HIF-1α i COX-2 w utkaniu guza oraz korelacja ze stopniem inwazyjnosci zmian nowotworowych u chorych z rakiem krtani--badania wstepne.

INTRODUCTION: Despite extensive research in the field of molecular biology, immunology and histopathology, prognostically unambiguous morphological indicators of the invasiveness of tumor which allow the prediction of disease course in laryngeal cancer have not yet been identified. The aim of this study was to analyze gene and protein expression of HIF-1a and COX-2 in the tumor stroma and to find relationships between clinical and morphological features (pT, G, depth of tumor invasion, plasmalymphocytic infiltration) and certain markers in squamous cell laryngeal carcinoma. MATERIAL AND METHODS: We analyzed a group of 59 patients with verified squamous cell carcinoma of the larynx. The pathological evaluation was included pTNM classification criteria, depth of invasion according to tumor front grading and degree of morphological differentiation. Quantitative analysis of the amplified product in real time (real-time RT2-PCR) for estimation of mRNA HIF-1a and COX-2 expression in tumor cells were used. The level of HIF-1a and COX-2 protein expression by Western blot analysis was determined. RESULTS: In studied group of laryngeal cancers significant differences in expression of certain molecules analyzed in tumor tissue and noncancerous epithelium of the larynx have been shown. Increased expression of HIF-1a and COX-2 at both mRNA and protein level was indicator of greater aggressiveness of the tumor, evaluated on the basis of clinical and morphological features in laryngeal squamous cell carcinomas. Tumors with the most invasive growth (pT4 stage, low-differentiated tumors G3, neoplastic infiltration with invasion of cartilage of the larynx) had the highest expression of HIF-1a and COX-2 at the mRNA and protein level. CONCLUSIONS: The study pointed out the direction for further research to find unambiguous indicators for estimation of tumor invasiveness and the possibility of practical use of HIF-1a and COX-2 mRNA and protein level assessment as important methods for determining the advancement of clinical and morphological changes in laryngeal cancer, thereby selecting an appropriate model of treatment.

[Expression of Foxp3 and RORgamma t in peripheral blood mononuclear cells in patients with laryngeal carcinoma as indicators of tumor stage--preliminary study]. / Ocena ekspresji Foxp3 i RORgamma t w jednojadrzastych komórkach krwi obwodowej u chorych z rakiem krtani jako wskazników zaawansowania zmian nowotworowych--badania wstepne.

INTRODUCTION: The degree of activation of cells involved in cellular immune response against tumor antigens (cytotoxic lymphocytes Tc) as well as efficiency of the mechanisms which promote immunosuppression (Treg - regulatory cells CD4(+)CD25(+)Foxp3(+)) may determine the course of the neoplastic disease. The aim of this study was to assess the function of autologous peripheral blood mononuclear cells (PBMCs) involved in the immunological processes on the basis of expression of Foxp3 and RORgamma t molecules as well as analysis of the relationships with clinical and morphological features of the tumor (pT and pN stage, G feature, degree of invasiveness according to the TFG classification) in laryngeal carcinoma. MATERIAL AND METHODS: The analysis included a group of 59 patients with verified squamous cell carcinoma of the larynx. In the pathologic evaluation pTNM classification criteria, depth of invasion and degree of histological differentiation were used. Expression levels of mRNA for Foxp3 and RORgamma t in peripheral blood mononuclear cells by quantitative analysis of the amplified product in real time (real-time RT(2)-PCR) were evaluated. The level of Foxp3 and RORgamma t protein expression by Western blot analysis was determined. RESULTS: In squamous cell carcinomas of the larynx, with the highest tumor aggressiveness the significantly highest level of mRNA and protein expression for Foxp3 molecule were observed. The severity of Foxp3 expression at both gene and protein level were positively linearly correlated with the degree of local extent of the tumor (pT3-4), depth of invasion (invasion of cartilage) and the degree of histological differentiation (low-differentiated tumors G3). In the study group of laryngeal cancers significantly lower level of RORgamma t expression in carcinomas with less invasive changes (pT1-2, high-differentiated tumors G1, carcinomas with microinvasion without evidence of invasion beyond the lamina propria) was also noted. CONCLUSIONS: The study results indicate the important role of immune cell activity as indicators of advancement of clinical and morphological changes in squamous cell carcinoma of the larynx.

Determination of stability constants and acute toxicity of potential hepatotropic gadolinium complexes.

Due to their high specificity for the hepatobiliary system, iminodiacetic acid derivatives are known to form a class of hepatobiliary agents. In this paper we present new hepatotropic gadolinium complexes to be used as potential MRI contrast agents. Derivatives of N-(2-phenylamine-2-oxoethyl) iminodiacetic acid are introduced as ligands into such complexes. In this way, we hope to achieve a valuable diagnostic tool for investigating of pathological changes in the liver. Stability constants of complexes were determined by potentiometric titration in 0.1 mol L(-1) NaNO3 solution at 20.0 +/- 0.1 degrees C. Stability and selectivity constants were also determined for endogenous metal ions such as Cu2+, Ca2+, and Zn2+ with the use of SUPERQUAD computer program. Acute toxicity of new gadolinium complexes was assessed in mice and histopathology examinations were carried out.

Immunoexpression of CAS protein is augmented in high grade serous ovarian tumors.

Ovarian cancer is one of the most important causes of death from gynecological malignancies in Poland. Recent investigations took a note of possible relationship between tumor histological grading and immunoexpression of apoptosis and proliferation related proteins in serous ovarian cancers. The aim of the study was to assess the immunoexpression of CAS protein in serous ovarian tumors of different histological grade, as well as to find possible relationships between this immunoexpression and tumor proliferation activity expressed by immuneexpression of Ki-67 protein. The analysis comprised of 66 women diagnosed and treated for malignant epithelial ovarian tumors. The immunoexpression of CAS protein was assessed semiquantitatively whereas immunoexpression of Ki-67 was performed using computer image analysis system. On immunohistochemical examinations it was found a significantly higher immunoexpression of both examined proteins in invasive serous ovarian cancers than in cystadenomas. Also, the significant positive correlation has been shown between immunoexpression of Ki-67 and CAS protein in particular group of tumors. In conclusion, our data suggest that increased immunoexpression of CAS protein in serous ovarian tumors may be useful in identifying the patients with more aggressive disease.

[Diagnostic and prognostic values of repair protein hMLH1, hMSH2 and protein CD34 immunoexpression in sporadic colorectal cancer]. / Znaczenie diagnostyczne i prognostyczne immunoekspresji bialek genów naprawczych hMLH1 i hMSH2 oraz blalka CD34 w sporadycznym raku jelita grubego.

UNLABELLED: Colorectal carcinoma is the most common gastrointestinal malignancy in the world. The survival of patients with colorectal cancer has not varied appreciably in recent years. The knowledge that genetic factors could play a role in the etiology and prognosis of patients with sporadic colorectal cancer has opened up new lines of research. The aim of the study was to evaluate a group of patients with colorectal cancer and the possible influence on the prognosis of immunohistochemical hMLH1, hMSH2 and CD34 expression. MATERIAL AND METHODS: 37 cases of colorectal cancer were included in this study. HMLH1, hMSH2 and CD34 protein expression in tumor tissue sections was determined using immunohistochemical staining with specific monoclonal antibodies. A total of 37 tumors were analyzed for histopathology. The immunoexpression status of MMR genes was correlated with cancer stage, location, histology, gender and CD34 immunoexpression. RESULTS: Of the 37 cases immunohistochemical analysis showed 13 (35.1%) had loss of expression of hMLH1, 5 (13.5%) had loss of expression of hMSH2, and five cases had loss of expression of both proteins. Multivariate analysis showed that right side dominance (p<0.05) poorly differentiated and male (p<0.05) were associated with loss of expression of hMLH1 or hMSH2. Loss of expression of hMLH1 or hMSH2 correlated with low CD34 expression (p>0.05). CD34 immunoexpression was higher in the left side tumor location, stage D Dukes'a (p<0.05) and G2 (p<0.05). CONCLUSIONS: These results confirm that sporadic colorectal MMR-defective adenocarcinomas display certain specific morphological characteristics. However, these pathological features are not sufficiently predictive and immunohistochemistry is needed to identify such tumours accurately. The researches on angiogenesis of cancer cells can be used as prognostic factors for the patients with colorectal cancer.

EGFR immunoexpression and peripheral blood cytokine secretion as potential biomarkers of tumor behavior in laryngeal squamous cell carcinoma.

BACKGROUND: Epidermal growth factor receptor (EGFR) and proinflammatory cytokines have been implicated in the dysregulated cell growth and increased aggressiveness of human cancers. The purpose of this study was to analyze EGFR immunoexpression in neoplastic tissues and IL-6 and TNFalpha secretion by peripheral blood mononuclear cells (PBMCs) and to investigate their relationships with certain clinicopathological characteristics. MATERIAL/METHODS: Tumor expression of membranous and cytoplasmic EGFR was measured in 45 cases of laryngeal squamous cell carcinoma by IHC staining. IL-6 and TNFalpha concentrations in 21-h PBMC cultures were measured by ELISA. Relationships between EGFR and cytokine secretion and clinicopathological characteristics such as pT status, pN status, and TFG classification, which include the parameters of the most invasive zones of neoplastic tissue and histological grade, were analyzed. RESULTS: The membranous EGFR index had a very strong association with pT stage, mode of invasion, and lymphocytic plasma infiltration of the tumor stroma. Relationships between the cytoplasmic EGFR index and nuclear polymorphism as well as TFG score for advanced carcinomas and histological grade in less invasive tumors were highlighted. The correlations of IL-6 and TNFalpha levels with TFG score, pT status, histological grade, and mode of tumor invasion were also significant. CONCLUSIONS: These findings confirmed the importance of EGFR immunoexpression rate as well as IL-6 and TNFalpha secretion by PBMCs as potential biomarkers for assessing the aggressive tumor phenotype in laryngeal carcinoma.

Impact of EGFR immunoexpression on STAT3 activation and association with proinflammatory/regulatory cytokine pattern in laryngeal squamous cell carcinoma.

Stimulation of epidermal growth factor receptor (EGFR) results in the activation of signal transducer and activator of transcription-3 (STAT3), a transcriptional factor associated with carcinogenesis. Proinflammatory cytokines are capable of activating a tumor cell death program by reducing EGFR tyrosine phosphorylation. This study aimed to identify EGFR expression in laryngeal carcinoma and determine the relationship with STAT3 and proinflammatory/regulatory cytokine secretion. An analysis of EGFR expression (membranous EGFR-m and cytoplasmic EGFR-c) was performed in tumor tissues by immunohistochemical (IHC) staining in 45 medical cases of laryngeal carcinoma. STAT3 expression in freshly isolated tumor and non-cancerous normal epithelial cells by RT-PCR was analyzed in 24 patients after total larynx resection. The concentrations of TNFalpha, IL-2, IL-6, IL-8 and IFNgamma secreted by purified peripheral blood mononuclear cells (PBMCs) or contained in whole blood samples were measured by ELISA. The relationship between EGFR and mRNA STAT3 expression as well as the level of secreted cytokines was investigated. In our study, 93.3% tumors expressed EGFR-m and 37.8% EGFR-c. It also revealed a statistically significant dependence of the EGFR status on STAT3 expression in neoplastic tissues. Tumors with IHC EGFR-m positive staining >50% of the total number of cells, as well as with EGFR-c positive staining, were characterized by the most frequent presence of STAT3 expression. Our data demonstrate a significant negative relationship between EGFR-m expression and TNFalpha concentration, and a positive connection between membranous EGFR and IL-8 or IFNgamma levels recorded in isolated PBMCs. Furthermore, this study revealed a significant relationship between EGFR-c immunoexpression and IL-8 or IFNgamma concentration. Our findings have confirmed a key role of EGFR in determining the proliferative and malignant potential of laryngeal carcinoma.

The inhibitory effect of diarylpropionitrile, a selective agonist of estrogen receptor beta, on the growth of MC38 colon cancer line.

The protective role of estrogens in the colon carcinogenesis has been suggested for many years and attributed mainly to estrogen receptor beta (ERbeta). However, the direct effect of estrogens and their action through ERbeta on the growth of colon cancer have been rarely studied. The aim of this study was to examine the effect of various concentrations (10(-4)-10(-12)M) of diarylpropionitrile (DPN)--a selective agonist of ERbeta--on the growth of murine MC38 colon cancer line. Moreover, the aim of this paper was the immunohistochemical assessment of estrogen and progesterone receptor expression in human colon tissues and in MC38 cells (only ERbeta). We found that DPN induced a growth inhibition of MC38 cancer (50-94% of control group) at the highest (10(-4)M) and two lowest concentrations (10(-11) and 10(-12)M). Furthermore, we detected a nuclear-cytoplasmic expression of ERbeta in human normal and neoplastic colon tissues and in the studied MC38 cancer cells. The inhibitory effect of DPN on the growth of MC38 colon cancer line suggests a possibility of using a selective estrogen receptor agonist in the treatment of colon cancer.

The expression of SOCS1 and TLR4-NFkappaB pathway molecules in neoplastic cells as potential biomarker for the aggressive tumor phenotype in laryngeal carcinoma.

Suppressor of cytokine signaling 1 (SOCS1) is the key regulator of cytokine-mediated innate and adaptive immunity. One of the molecular mechanisms of SOCS1 is connected with inhibition of TLR4-NFkappaB pathway. The relationships among these molecules in laryngeal carcinoma are not exactly known. In this preliminary study we focused on their special activity and role in regulation of development and progression of laryngeal carcinoma. To investigate NFkappaB (p65 subunit) nuclear and cytoplasmic expression in 45 tumor samples of advanced laryngeal carcinoma IHC staining was performed. To determine the mRNA expression levels of TLR4, IRAK1, TRAF6 and SOCS1 in isolated neoplasm cells and non-cancerous adjacent mucosa epithelial cells RT-PCR was used. The invasiveness of laryngeal carcinomas was evaluated according to tumor front grading, TFG, which included tumor-related features (cytoplasmic differentiation, nuclear polymorphism, number of mitoses) and adjacent stroma-related characteristics of the peripheral edge of tumor infiltration (mode of infiltration, depth of invasion and plasmalymphocytic infiltration). The relationships between pT, pN status, the histological G grade, certain clinicopathological characteristics as well as postoperative observation time and the mRNA expression of the molecules mentioned earlier were investigated. Significant differences of TLR4-NFkappaB pathway molecules and SOCS1 mRNA expression in laryngeal tumor cells and normal adjacent mucosa cells as well as significant interconnections of TLR4, SOCS1 and NFkappaB(p65) in isolated tumor cells were obtained. This preliminary study demonstrated that the expression of SOCS1 and TLR4-NFkappaB pathway molecules had a strong association with the aggressiveness of laryngeal carcinoma. Positive relationships of TRAF6 in tumor margin cells with the histological grade and the mode of tumor invasion as well as the TFG total score were highlighted. Significant positive correlations were found between the TLR4 in tumor central cells and the TFG total score. Negative relationships of SOCS1 in tumor central cells with the histological grade were also noted. Significant positive correlations were found between the cytoplasmic NFkappaB(p65) and the mode of invasion as well as TFG total score. Our findings confirmed the importance of SOCS1 and TLR4-NFkappaB pathway molecules as potential biomarkers for assessment of the aggressive tumor phenotype in laryngeal carcinoma.

[Expression of transcription nuclear factor NFkappaB in laryngeal carcinoma tumor cells--correlation with IL-10 expression by blood mononuclear cells and clinicomorphological features]. / Ekspresja transkrypcyjnego czynnika jadrowego NFkappaB w komórkach raka krtani--korelacja z ekspresja IL-10 oraz cechami kliniczno-morfologicznymi guza.

PURPOSE: Transcription nuclear factor NFkappaB (p65-p50/RelA) is an activator of transcription process and regulates the apoptosis, cell cycle, proliferation, secretion of cytokines, angiogenic and growth factors by initiation gene transcription. NFkappaB can be activated by signaling pathway following IL-10 stimulation. The aim of this study was to estimate NFkappaB cytoplasmic and nuclear immunoexpression and to analyze the connection with clinicopathological features and IL-10 concentration produced by blood mononuclear cells in patients with laryngeal carcinoma. MATERIALS AND METHODS: Analysis of NFkappaB expression by immunmohistochemistry and IL-10 production by PBMCs and measured by Elisa in 45 patients with squamous cell carcinoma of the larynx were performed. Connections NFkappaB immunoexpression with clinicomorphological features (pT, pN, Anneroth, Batsakis i Lunas' classification) and IL-10 secretion were analyzed. RESULTS: Authors reported statistical correlation between NFkappaB cytoplasmic level and clinicomorphological parameters such as neoplasm advance according to Anneroth, Batsakis i Lunas' classification and depth of invasion as well as IL-10 secretion by PBMCs. CONCLUSION: Our studied indicated the important influence of NFkappaB activity on advance in laryngeal carcinoma as well as connection of anti-inflammatory and regulatory cytokine IL-10 produced by immunocompetent cells for course of neoplasm disease.

[Production of cytokines by peripheral blood mononuclear cells--correlation with clinicomorphological features in laryngeal carcinoma]. / Wydzielanie wybranych cytokin przez monocytarne komórki krwi--korelacja z cechami kliniczno-morfologicznymi w raku krtani.

INTRODUCTION: In studied analyzed role of the cytokines in pathology of neoplasms of various origin the importance of these proteins in regulation of immunocompetent cells function has been described. The aim of this study was to estimate of cho sen cytokines concentration produced by peripheral blood mononuclear cells and in whole blood in patients with laryngeal carcinoma and to analyze the connection of cytokines profile with clinicopathological features. MATERIALA AND METHODS: 55 patients with squamous cell carcinoma of the larynx treated at ENT Department Medical University of Lodz between 2003-2007 were analyzed. For estimation of cytokine secretion the cultures of isolated peripheral blood mononuclear cells (T lymphocytes) and the whole blood were established. Production of cytokines in supernatants was detected by Elisa. Connections with clinicomorphological features (pT, pN, Anneroth, Batsakis i Lunas' classification) were analyzed. RESULTS: Authors reported statistical correlation between chosen cytokines concentration and clinicomorphological parameters: pT and IL-2, IL-6, IL-8, TNFalpha produced by isolated cells and IL-2, IL-6, TNFa and IFNgamma in whole blood, pN and IL-8, IL-10, IFNgamma; ABL score and IL-6, TNFalpha, IFNgamma produced by isolated cells and IL-2, IL-6, IL-10, TNFalpha, IFNgamma in whole blood. CONCLUSION: Our studied indicated the important influence of proinflammatory and regulatory cytokines produced by immunocompetent cells for course of neoplasm disease, aggressiveness and advance in laryngeal carcinoma.

Immunoexpression of beta-catenin--E-cadherin complex in primary serous ovarian tumors.

Ovarian cancer takes a fourth place as cause of death from all cancers and a first place from gynecologic malignancies in Poland. Up to now, relatively little is known about immunohistochemical markers accepted as prognostic indicators for ovarian cancers. Recent investigations took a note of prognostic significance of catenin-cadherin adhesion complex and Ki-67 proliferation protein in serous ovarian cancers. The aim of the study was to evaluate the immunoexpression of beta-catenin and E-cadherin in metastatic and nonmetastatic serous ovarian tumors, as well as to find possible relationships between this immunoexpression and tumor proliferation activity. The analysis comprised of 66 women diagnosed and treated for epithelial ovarian tumors. On immunohistochemical examinations it was found a significantly lower immunoexpression of beta-catenin and E-cadherin in invasive serous ovarian cancers than in cystadenomas. Additionally, in metastatic group the immunoexpression of both beta-catenin and E-cadherin was significantly decreased as compared with patients without metastases. Moreover, the significant inverse correlations have been shown between immunoexpression of Ki-67 and beta-catenin as well as Ki-67 and E-cadherin. In conclusion, our data suggest that decreased immunoexpression of beta-catenin and E-cadherin in serous ovarian tumors may be helpful in identifying the cases of higher metastatic potential and infiltration ability.

[Correlation of membrane type I matrix metalloproteinase (MT1-MMP) expression with clinicomorphological features of tumor front in squamous cell carcinoma of the larynx]. / Korelacja ekspresji metaloproteinazy blonowej macierzy zewnatrzkomórkowej typu I (MT1-MMP) we froncie nacieku nowotworowego z cechami kliniczno--morfologicznymi w raku plalkonablolkowym krtani.

UNLABELLED: Matrix metalloproteases (MMPs) are proteolytic enzymes contribute to tumor expansion by degrading components of the extracellular matrix. MPPs play a key role in tumor invasion and metastases of various cancers and head and neck carcinoma as well. The aim of this study was to investigate MT1-MMP expression in squamous cell carcinoma of the larynx to relate these levels of expression to clinicohistological features of the tumor and lymph nodes e.g. TNM, nodal micrometastases, tumor front grading and 3- and 5-year survival. MATERIAL AND METHODS: The study included 22 patients with laryngeal cancer surgical treated in ENT Department Medical University of Lódz between 1998 and 1999. The expression of MT1-MMP was evaluated immunohistochemically using monoclonal antibodies anti-MT1-MMP (Mouse Anti-Human MT1-MMP, MAB3319 Chemicon). The polyclonal antibodies anti-CK for developing nodal micrometastases was used as well. RESULTS: Positive MT1-MMP expression in 68.2% cases was observed. Immunoexpression of MT1-MMP in advanced laryngeal carcinoma as indicator for 3-year survival was noted. In addition, levels of staining correlated with number of mitoses in tumor front and plasmocytolymphatic infiltration in its environment. CONCLUSIONS: The expression of MT1-MMP in tumor front appears to play an important role in determining prognosis in patients with carcinoma of the larynx.

The significant role of RANTES and CCR5 in progressive tubulointerstitial lesions in lupus nephropathy.

Glomerulonephritis is an important cause of end-stage renal failure, yet the pathogenetic mechanisms of most forms of glomerulonephritis are not clear. Renal fibrosis is the final common pathway for many kidney lesions that lead to chronic progressive organ failure. Recent study suggests that chemokines and chemokine receptors are involved in the resolution or progression of renal diseases. In view of the above we detected using immunohistochemistry the expression of RANTES, CCR5+ cells,TGF-beta1, alpha-SMA in renal biopsy specimens in 17 patients with IVG A/C class of lupus nephritis and in 10 normal kidneys. The correlative study was undertaken to evaluate the possible relationships between the immunoexpression of RANTES, the number of CCR5+ cells, the immunoexpression of TGF-beta1, alpha-SMA, the value of interstitial cortical volume and the serum creatinine level in patients with lupus nephropathy. Statistical analysis revealed significant increase in tubulointerstitial RANTES immunoexpression in lupus nephritis as compared to normal controls. In our study CCR5+ cells were detected in the interstitium in tissue samples in patient with lupus nephritis, meanwhile no CCR5+ cells were documented in normal controls. We found a strong positive correlation between tubulointerstitial immunoexpression of RANTES and the number of interstitial CCR5+ cells as well as between immunoexpression of RANTES and the immunoexpression of TGF-beta1, alpha-SMA, renal cortical volume and serum creatinine in patients with lupus nephritis. Moreover, the number of interstitial CCR5+ cells was positively correlated with tubulointerstitial alpha-SMA immunoexpression and renal cortical volume. In summary, the results suggest that in lupus nephritis RANTES may participate in interstitial lesions via CCR5+ cells.

Transforming growth factor beta 1 and metalloproteinase-9 overexpression in colorectal cancer (CC) and adenoma.

BACKGROUND AND AIMS: Although the role of transforming growth factor beta (TGFbeta) 1 and metalloproteinase-9 (MMP-9) is well documented in colorectal cancer (CC), there is a little evidence supporting its role in early carcinogenesis. The aim of the study was to determine the pattern of immunohistochemical expression of TGFbeta1, MMP-9, and Ki-67 in CC and adenomatous polyps. PATIENT/METHODS: The study group comprised 50 patients with colorectal polyps and 33 patients with CC. Endoscopically removed polyps and CC biopsies had been evaluated with histopatologic examination and immunohistochemistry. The biopsies from 30 healthy objects served as a control group. For all antibodies labeling indices (LI) had been calculated. RESULTS: Among 62 adenomas, 33 high-grade dysplasia (HGD) and 29 low-grade dysplasia (LGD) had been detected. Mean TGFbeta1, MMP-9, and Ki-67 LI in CC were significantly higher (p < 0.01, 0.01, and 0.01, respectively) than in HGD polyps. Mean TGFbeta1, MMP-9, and Ki-67 LI in HGD polyps were significantly higher than in LGD polyps (p < 0.01, 0.01, and 0.01, respectively). There had been no statistical difference in TGFbeta1, MMP-9, and Ki-67 LI between LGD and the control group (p > 0.05, 0.05, and 0.05, respectively). There was a positive correlation between TGFbeta1 and MMP-9 (r = 0.898), Ki-67 and MMP-9 (r = 0.938), and TGFbeta1 and Ki-67 (r = 0.913). We did not observe any correlation between TGFbeta1, MMP-9, Ki-67 LI and the clinical parameters evaluated. CONCLUSION: The increased expression of TGFbeta1, MMP-9 observed in colorectal adenomas seems to be related to the grade of dysplasia. We assume that overexpression of TGFbeta1, MMP-9 represent an early event in colorectal carcinogenesis and may possibly have the prognostic value.

Chemokines and chemokine receptors in glomerulonephritis and renal allograft rejection.

Infiltration by mononuclear cells is found within the renal tissue in various types of kidney diseases. The migration of leukocytes through vessels and beyond the vascular compartment is dependent in part on small chemoattractant proteins called chemokines. All types of renal cells can produce chemokines in a cell- and stimulus-specific manner. Some chemokines appear to be constitutively expressed, while proinflammatory chemokines are expressed only in responses to specific stimuli. MCP-1 expression in renal tubuli is enhanced in proteinuric states, irrespective of the types of renal disease, and this increased MCP-1 expression probably contributes to renal tubular damage in proteinuric states. Expression of individual chemokines correlate with intrarenal T cells and monocyte/macrophage infiltrates as well as with interstitial kidney damage and renal function. Experimental data and studies on human renal tissue in patients with glomerulonephritis and renal allograft rejection indicate that MCP-1, MIP-lalpha, beta, RANTES, and IL-8 play a main role in the resolution and progression of inflammatory processes in these cases. Renal cells and inflammatory cells also express chemokine receptors, especially CCR-5, CCR-1, CCR-2, and CXCR3. Analysis of the immunoexpression of chemokines and chemokine receptors in renal tissue of patients with glomerulonephritis and renal allograft rejection may be helpful in evaluating the progression of kidney disease, whereas monitoring chemokines in the urine may provide a dynamic picture of the inflammatory state. The pharmacological regulation of chemokine and chemokine receptor expression may be a useful tool in the therapy of kidney diseases.

[Clinico-histopathological characteristic of inverted papilloma of nasal cavity and paranasal sinuses cases treated in Department of Laryngological Oncology UM of Lodz between 2002-2006--review of latest literature]. / Kliniczno-histopatologiczna charakterystyka przypadków brodawczaka odwróconego jam nosa i zatok przynosowych leczonych w Klinice Laryngologii Onkologicznej UM w Lodzi w latach 2002-2006--przeglad najnowszego pismiennictwa.

Authors introduced diagnostic procedures, clinico-morphological features and treatment results of 16 cases of nasal cavity and paranasal sinuses inverted papillomas treated surgically on Department of Laryngological Oncology of Medical University of Lodz between 2002-2006. References review, definition, classification, clinico-hiostopathological criteria and treatment methods of Schneiderian papilloma were introduced in study.

[Morphological tumor front grading and matrix metalloproteinases type I expression as a prognostic parameter of the presence of lymph node micrometastases in laryngeal carcinoma]. / Morfologiczna ocena nacieku nowotworowego oraz ekspresji metaloproteinazy blonowej macierzy zewnatrzkomórkowej typu I jako prognostyczny wskaznik powstawania mikroprzerzutów w raku krtani.

INTRODUCTION: Occult foci of neoplasm cells in lymph nodes (referred to as micrometastases) in various squamous cell carcinomas may be discovered by immunohistochemistry by using anti-CKs (cytokeratine filaments) policlonal antibodies which reactive with epithelial cells. Matrix metalloproteinases (MMPs) are proteolytic family enzymes represent a group of endopeptidases which are capable to degrading components of the extracellular matrix and have been implicated as playing an important role in cancer invasion and metastases. The purpose of this study was to analyze the morphological parameters and to investigate MT1-MMP expression in laryngeal carcinoma to relate the expression to CKs in pN0 lymph nodes. MATERIALS AND METHODS: To presented the direct correlation between the morphological features of tumor front and the probability of micrometastases and prediction of prognosis we have analyzed 22 patients operated for squamous cell carcinoma of the larynx. The total score of TFG classification, tumor clinicomorphological features and grade of matrix metalloproteinase membrane type 1 staining in tumor front were analyzed to predict the presence of micrometastases and prognosis. Immunohistochemical methods with a panel of CKs antigens in lymph nodes and MT1-MMP expression in tumor tissue were performed. RESULTS: Our study showed that the total morphologic score TFG is very useful in the prediction of micrometastases in patients with laryngeal squamous cell carcinoma. The statistical analysis has revealed a significant correlation between the total TFG score and the depth of invasion and the presence of micrometastases. Positive MT1-MMP expression in 68.2% cases was observed. There was no significant relationship for immunoexpression of MT1-MMP in examined group of patients with advanced laryngeal carcinoma and positive poliCKs stain in lymph nodes. CONCLUSIONS: The results of study suggest that extended traditional pathologic evaluation by features from the TFG classification, especially the depth of invasion, could aid in diagnosis of micrometastases. The positive expression of poliCKs in the conventional pathological examination of pN0 lymph nodes appears to play an important role in determining prognosis in patients with carcinoma of the larynx.

Immunoexpression of podocyte-associated proteins in acquired human glomerulopathies with nephrotic syndrome.

CD2AP, alpha-actinin-4 and podocalyxin are thought to play an important role in the structure and function of glomerular podocytes, therefore we intended to evaluate quantitatively, using computer image analysis system, the immunoexpression of these proteins in renal biopsy specimens in glomerulopathies presented with nephrotic syndrome: minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS) and nephropathy IgA (IgAN). As a control 10 biopsy specimens of the kidneys removed because of trauma were used. In normal kidneys CD2AP, alpha-actinin-4, and podocalyxin showed intense staining in podocytes along the capillary walls of the glomeruli. The intensity of immunoexpression of CD2AP and alpha-actinin-4 in renal tissue in patients with MCD, FSGS, and IgAN was similar to normal controls, but the distribution of these proteins was more granular in glomeruli of diseased kidney. The immunostaining of podocalyxin was weaker in podocytes in patients with FSGS as compared with normal glomeruli. The immunostaining of podocalyxin was not significantly altered in MCD and IgAN. The immunostaining of CD2AP and alpha-actinin-4 did not correlate with the intensity of proteinuria in patients with MCD, FSGS and IgAN, whilst in FSGS patients the significant correlation was found between the glomerular immunostaining of podocalyxin and proteinuria. In conclusion, revealed in our study diminished immunoexpression of podocalyxin and significant correlation with the level of proteinuria in FSGS patients suggests a possible role of this sialoprotein in the alteration of the glomerular filtration barrier in this disease.