Expression of the Selected Proteins of JAK/STAT Signaling Pathway in Diseases with Oral Mucosa Involvement.

The JAK/STAT signal pathway is a system of intracellular proteins used by many cytokines and growth factors to express genes responsible for the process of cell activation, proliferation and differentiation. There has been numerous inflammatory and autoimmune diseases identified where the JAK/STAT signaling is disrupted; however, there are only a few papers concerning autoimmune bullous diseases published. The aim of this study was to evaluate the expression of proteins: JAK3, STAT2, STAT4 and STAT6 in epithelium lesions in patients with pemphigus vulgaris (PV), bullous pemphigoid (BP), oral lichen planus (LP) and chronic ulcerative stomatitis (CUS), as well as in the control group. Immunohistochemistry and immunoblotting were used to evaluate expression of selected proteins. We found significantly higher expression of selected JAK/STAT proteins in oral mucosa lesions in study groups in comparison to the control group, which indicates participation of JAK/STAT pathway in pathogenesis of these diseases. In BP and PV there were no increased STAT2 expression, whereas in CUS and LP no increased STAT4 expression occurred. The differences in expression of JAK/STAT proteins in selected disorders have been observed. These results create new potential therapeutic targets for the treatment.

Close relationship between TAZhigh/SOX2high co-localization and metastasis in oral squamous cell carcinoma.

There is growing evidence which indicates that the development and the biological features of cancer such as the invasion, metastases and recurrence are related to the presence and behavior of the cancer stem cells (CSC). However, the regulatory mechanisms underlying CSCs-specific properties are poorly determined, the Hippo pathway has emerged as a fundamental regulator underlying CSCs stemness. Immunohistochemical method was used to examine the immunoexpression of SOX2, TAZ and α-SMA in oral squamous cells carcinomas: with metastases - OSCC M+ (n = 42), and without metastases - OSCC M- (n = 44), and 17 control cases. The immunoexpression of SOX2, TAZ and α-SMA was significantly increased in both group of OSCC in comparison to control groups. Moreover, significantly increased TAZ and α-SMA immunoexpression were found in OSCC M+ compared to OSCC M-. In OSCC M+ and OSCC M- groups there were statistically significant correlations between the immunoexpression of TAZ vs SOX2 (r = 0.56, p < 0.001; r = 0.33, p < 0.03 respectively), and TAZ vs α-SMA (r = 0.64, p < 0.001; r = 0.67, p < 0.001 respectively). Moreover, there was statistically significant association between TAZ high /SOX2 high coexistent immunoexpression and the presence of metastases (p < 0.007). Our results may suggest that SOX2 and TAZ could potentially cooperate and contribute to process of metastasis, especially in cases with TAZ high /SOX2 high expression.

Maltotriose-modified poly(propylene imine) Glycodendrimers as a potential novel platform in the treatment of chronic lymphocytic Leukemia. A proof-of-concept pilot study in the animal model of CLL.

Cancer nanotherapeutics have shown promise in resolving some of the limitations of conventional drug delivery systems such as nonspecific biodistribution and targeting, lack of water solubility, and low therapeutic indices, Among the various nanoparticles that are available, dendrimers, highly branched macromolecules with a specific size and shape, are one of the most promising ones. In this preliminary study, we tested the anti-tumor activity of maltotriose-modified fourth-generation poly(propylene imine) glycodendrimers (PPI-G4-M3) in vivo in the subcutaneous MEC-1 xenograft model of human chronic lymphocytic leukemia (CLL) in NOD scid gamma mice. Fludarabine was used for model validation and as a positive treatment control. The anti-tumor response was calculated as tumor volume, tumor control ratio, and tumor growth inhibition. The study showed that PPI-G4-M3 inhibited subcutaneous tumor growth more efficiently than fludarabine. The anti-tumor response was dose-dependent. Cationic PPI-G4-M3 showed the highest anti-tumor activity but also higher toxicity than the neutral dendrimers and fludarabine. These first promising results warrant further studies in the optimization of dendrimers charge, dose, route and schedule of administration to combat CLL.

Overexpression of cathepsin K and vascular endothelial growth factor in chronic venous ulcerations.

INTRODUCTION: Chronic venous disease (CVD) is a disabling condition affecting about 1% to 3% of the general population. Besides varicose veins, CVD can result also in the formation of severe skin lesions, especially venous ulcerations (VU). The exact mechanism of VU is still unknown. AIM: To evaluate immunoexpression of vascular endothelial growth factor (VEGF) and cathepsin K in healthy individuals and patients with VU. MATERIAL AND METHODS: The study included 12 patients with venous ulcers and 10 healthy individuals who served as controls; both groups were sex- and age-matched. Biopsy samples were obtained from lower leg areas and submitted to histochemical analysis. RESULTS: There was a significant difference between the study group and the control group in cathepsin K expression (1.007 ±0.3 vs. 0.22 ±0.2, respectively, p < 0.001) and VEGF expression (1.17 ±0.59 vs. 0.27 ±0.19, respectively, p < 0.001). Additionally, the microvessel density (per mm2) differed significantly between the study group and the control group (97.6 ±28.81 vs. 59.32 ±12.71, respectively, p < 0.001). We found no correlation between cathepsin K and microvessel density, and cathepsin K and VEGF in both groups, but there was a significant correlation between microvessel density and VEGF immunoexpression in the study group (r = 0.82, p = 0.002). CONCLUSIONS: Increased immunoexpression of VEGF and cathepsin K suggests that both of these proteins may play a role in VU development.

The number of CD163 positive macrophages is associatedwith more advanced skin melanomas, microvessels density and patient prognosis.

The study was aimed to evaluate the number of TAMs and to investigate whether they have association with microvessels density and patients' survival times. 46 cases of melanomas, divided into four groups according to the Breslow scale, were tested immunohistochemically with antibodies anti-CD68, CD163, iNOS to vizualized macrophages and anti-CD34 antibody to stain microvessels. The number of macrophages and the microvessels density were counted by hotspot analysis using an image analysis system. The study revealed increased numbers of CD68 and CD163 positive macrophages in successive stages of Breslow scale, but statistically significant differences were observed only between I and IV group for CD68 positive macrophages, and between I and III, IV group for CD163 positive macrophages. The mean number of the microvessels was significantly increased in group II, III, IV compared to group I. The correlative study showed significant positive correlations between the mean number of CD68 and CD163 positive macrophages and microvessels density. Moreover, the number of CD163 positive macrophages was associated inversely with patient's survival time. The results of our study may indicate that higher infiltration of macrophages, especially CD163 positive cells, is associated with more advanced melanomas, microvessels density and worse patient's prognosis.

T cells are involved in the induction of macrophage phenotypes in oral leukoplakia and squamous cell carcinoma-a preliminary report.

BACKGROUND: The prognosis of human malignancies has been shown to depend on immunological parameters, such as macrophage polarization (M1 and M2). In this study, we identify the phenotype of macrophages, and investigate an involvement of infiltrated T cells that participate in the polarization of macrophages, in oral leukoplakia (OLK), and oral squamous cell carcinoma (OSCC). METHODS: Immunohistochemical method was used to examine the number of CD68+ , CD163+ (M2), iNOS+ (M1) macrophages, and CD4+ , CD8+ , CCR4+ (Th2), CCR5+ (Th1) cells in 102 cases of OSCC: without metastases-OSCC M(-) (n = 54), and with metastases-OSCC M(+) (n = 48), 23 cases of OLK, and 18 control cases. RESULTS: The mean number of CD68+ , CD163+ , iNOS+ , CD4+ , CCR4+ , CCR5+ cells was significantly increased in OSCC M(+) group compared with OLK, OSCC M(-) and control group. We found positive correlations between the number of CD4+ T cells and CD163+ and iNOS+ macrophages as well as CCR4+ and CCR5+ cells in both OSCC groups. The mean number of CD8+ cells was significantly increased in OSCC M(-) and OLK compared with OSCC M(+) and control group. In OSCC M(+) and OSCC M(-) groups, a negative correlation between the number of CD8+ cells and CD163+ and iNOS+ macrophages was found. CONCLUSIONS: The number and co-localization of lymphocytes and macrophages in OLK and OSCC may indicate that infiltrating cells influence the early and subsequent stage of oral carcinogenesis.

Overexpression of ADAM10 in oral squamous cell carcinoma with metastases.

ADAMs (a disintegrin and metalloproteinase) are important mediators of cell signalling events, which play a role in the pathogenesis and progression of cancers. Immunohistochemical method was used to examine the immunoexpression of ADAM10 and microvessel density in 80 cases of oral squamous cell carcinoma (OSCC): without metastases - OSCC M(-) (n = 38), and with metastases - OSCC M(+) (n = 42), in 24 cases of oral leukoplakia (OLK), (15 cases with low-grade dysplasia - OLK-LG, and 9 cases with high-grade dysplasia - OLK-HG), and 19 controls. The immunoexpression of ADAM10 and the mean number of vessels were significantly increased in both groups of OSCC in comparison to both groups of OLK and controls. Moreover, the immunoexpression of ADAM10 and microvessel density were significantly increased in the OSCC M(+) group in comparison to the OSCC M(-) group. No statistically significant differences were found between immunoexpression of ADAM10 and microvessels density in the OLK-LG, OLK-HG, and control cases. In conclusion, the present study revealed overexpression of ADAM10 in OSCCs, especially in OSCC with metastasis. These findings suggest that ADAM10 could potentially contribute to metastases of oral cancer. Although, our findings suggest that ADAM10 may be involved in angiogenesis of OSCC, further studies are required to determine the role of ADAM10 in this process.

Clinicopathologic correlations of renal pathology in the adult population of Poland.

BACKGROUND: This is the first report on the epidemiology of biopsy-proven kidney diseases in Poland. METHODS: The Polish Registry of Renal Biopsies has collected information on all (n = 9394) native renal biopsies performed in Poland from 2009 to 2014. Patients' clinical data collected at the time of biopsy, and histopathological diagnoses were used for epidemiological and clinicopathologic analysis. RESULTS: There was a gradual increase in the number of native renal biopsies performed per million people (PMP) per year in Poland in 2009-14, starting from 36 PMP in 2009 to 44 PMP in 2014. A considerable variability between provinces in the mean number of biopsies performed in the period covered was found, ranging from 5 to 77 PMP/year. The most common renal biopsy diagnoses in adults were immunoglobulin A nephropathy (IgAN) (20%), focal segmental glomerulosclerosis (FSGS) (15%) and membranous glomerulonephritis (MGN) (11%), whereas in children, minimal change disease (22%), IgAN (20%) and FSGS (10%) were dominant. Due to insufficient data on the paediatric population, the clinicopathologic analysis was limited to patients ≥18 years of age. At the time of renal biopsy, the majority of adult patients presented nephrotic-range proteinuria (45.2%), followed by urinary abnormalities (38.3%), nephritic syndrome (13.8%) and isolated haematuria (1.7%). Among nephrotic patients, primary glomerulopathies dominated (67.6% in those 18-64 years of age and 62.4% in elderly patients) with leading diagnoses being MGN (17.1%), FSGS (16.2%) and IgAN (13.0%) in the younger cohort and MGN (23.5%), amyloidosis (18.8%) and FSGS (16.8%) in the elderly cohort. Among nephritic patients 18-64 years of age, the majority (55.9%) suffered from primary glomerulopathies, with a predominance of IgAN (31.3%), FSGS (12.7%) and crescentic GN (CGN) (11.1%). Among elderly nephritic patients, primary and secondary glomerulopathies were equally common (41.9% each) and pauci-immune GN (24.7%), CGN (20.4%) and IgAN (14.0%) were predominant. In both adult cohorts, urinary abnormalities were mostly related to primary glomerulopathies (66.8% in younger and 50% in elderly patients) and the leading diagnoses were IgAN (31.4%), FSGS (15.9%), lupus nephritis (10.7%) and FSGS (19.2%), MGN (15.1%) and pauci-immune GN (12.3%), respectively. There were significant differences in clinical characteristics and renal biopsy findings between male and female adult patients. CONCLUSIONS: The registry data focused new light on the epidemiology of kidney diseases in Poland. These data should be used in future follow-up and prospective studies.

The utility of glomerular C4d immunostaining in renal biopsies in patients with immunoglobulin A nephropathy. A clinicopathological study.

The course of IgA nephropathy (IgAN) is highly variable and ranges from a totally benign condition to end-stage renal disease in approximately one third of cases. The identification of new prognostic markers could provide insights into the pathogenesis of IgAN and unveil new therapeutic avenues. Glomerular deposition of C4d is a marker of activation of the lectin pathway of complement. It is thought that activation of the lectin pathway in IgAN is associated with more severe renal damage, and more severe histological findings. In view of the above, the aim of the present study was to compare the clinical presentation, laboratory data, and histological lesions in the renal biopsy in IgAN patients with positive and negative staining for mesangial C4d depositions. Our study revealed that hypertension, severe proteinuria, a high level of serum creatinine, low eGFR at the time of presentation, as well as tubular atrophy/interstitial fibrosis > 50%, and endocapillary proliferation were significantly more frequent in the C4d (+) group than in the C4d (-) group. Based on our research, we can assume that mesangial immunoexpression of C4d seems to be a useful prognostic factor in IgAN.

Association of infiltrating cells with microvessel density in oral squamous cell carcinoma.

Several lines of evidence indicate that immune cells in the tumor microenvironment play an important role in regulating tumor progression. An immunohistochemical method was used to examine the abundance of natural killer (NK) cells, mucosal dendritic cells (DCs), macrophages, mast cells, and microvessel density in 78 cases of oral squamous cell carcinoma (OSCC): with better prognosis - OSCCBP (n = 37), and with poorer prognosis - OSCCPP (n = 41), and 18 controls. The mean numbers of macrophages and microvessels were significantly higher in the OSCCPP group in comparison to both OSCCBP and control groups. The mean number of NK cells, mast cells and DCs was lower in the OSCCPP group in comparison to the OSCCBP group, but there were no statistically significant differences between mean numbers of NK cells in tested groups. Statistically significant correlations between the number of DCs and NK cells and mast cells, as well as between microvessel density and numbers of macrophages, DCs and mast cells were revealed in both OSCCPP and OSCCBP groups. In conclusion, our findings revealed an association between the number of infiltrating cells and oral cancer prognosis. Moreover, our results suggest that the infiltrating cells (macrophages, Langerhans and mast cells) may be involved in the process of angiogenesis.

Perirenal perivascular epithelioid cell tumor (PEComa) coexisting with other malignancies: a case report.

Perivascular epithelioid cell tumor (PEComa) is a very rare lesion and is described by the World Health Organization (WHO) as a mesenchymal tumor composed of histologically and immunohistochemically distinctive perivascular epithelioid cells. In this report we describe PEComa with perirenal manifestation, which is exceedingly rare and to our best knowledge up to now worldwide only three cases have been described. Despite the reports that most PEComas are benign, this tumor met criteria for malignancy and coexisted with mucinous gallbladder cancer and nonresectable pancreatic head tumor. We concluded that despite the rarity of perirenal PEComas, in cases with an unusual epithelioid histological pattern the diagnosis of PEComa should also be taken into consideration on the basis of the immunohistochemical study.

Biological evaluation of the toxicity and the cell cycle interruption by some benzimidazole derivatives.

In this work, the in vitro tests of biological activity of benzimidazoles were conducted. This group of benzimidazole derivatives was evaluated as potential bioreductive agents and their characteristic pro-apoptosis activity and cell cycle interruption on the human lung adenocarcinoma A549 cells were discussed. Their toxicity on the healthy human erythrocytes and their influence on the healthy human erythrocytes acetylcholinesterase enzyme (AChE) were established. Their apoptosis activity on A549 cells line was determined by Annexin V-APC test, and it was visualized by Hoechst test. In the next stage, their influence on the cell cycle interruption was determined by using the ribonuclease reagent. The AChE inhibition test was defined by the Ellman method, and the red blood cell lysis was defined by erythrotoxicity test. The results proved the pro-apoptosis properties of all tested compounds in normoxia and hypoxia. The DNA content assay showed that the benzimidazoles possess the ability to interrupt S phase of tumor cell cycle. The best activity in this action was presented by compound 1, especially in hypoxia, and it proves that the N-oxide analogs are predispositioned to the hypoxic target. In this study, the benzimidazoles were found as potentially biocompatible and their inhibition of acetylcholinesterase was lower than tirapazamine and much lower than tacrine which constitutes their desired effect of potential biological activity.

Gene/protein expression of CAPN1/2-CAST system members is associated with ERK1/2 kinases activity as well as progression and clinical outcome in human laryngeal cancer.

Recent evidence indicates the involvement of calpains (CAPNs), a family of cysteine proteases, in cancer development and progression, as well as the insufficient response to cancer therapies. The contribution of CAPNs and regulatory calpastatin (CAST) and ERK1/2 kinases to aggressiveness, disease course, and outcome in laryngeal cancer remains elusive. This study was aimed to evaluate the CAPN1/2-CAST-ERK1/2 enzyme system mRNA/protein level and to investigate whether they can promote the dynamic of tumor growth and prognosis. The mRNA expression of marker genes was determined in 106 laryngeal cancer (SCLC) cases and 73 non-cancerous adjacent mucosa (NCLM) controls using quantitative real-time PCR. The level of corresponding proteins was analyzed by Western Blot. SLUG expression, as indicator of pathological advancement was determined using IHC staining. Significant increases of CAPN1/2-CAST-ERK1/2 levels of mRNA/protein were noted in SCLC compared to NCLM (p < 0.05). As a result, a higher level of CAPN1 and ERK1 genes was related to larger tumor size, more aggressive and deeper growth according to TFG scale and SLUG level (p < 0.05). There were also relationships of CAPN1/2 and ERK1 with incidences of local/nodal recurrences (p < 0.05). An inverse association for CAPN1/2, CAST, and ERK1/2 transcripts was determined with regard to overall survival (p < 0.05). In addition, a higher CAPN1 and phospho-ERK1 protein level was related to higher grade and stage (p < 0.05) and was found to promote worse prognosis. This is the first study to show that activity of CAPN1/2- CAST-ERK1/2 axis may be an indicator of tumor phenotype and unfavorable outcome in SCLC.

Atrophy of type I and II muscle fibers is reversible in the case of grade >2 fatty degeneration of the supraspinatus muscle: an experimental study in rabbits.

BACKGROUND: Although clinical investigations indicate that the limit of reversibility of rotator cuff muscles fibers type I and II atrophy is grade 2 of fatty degeneration (FD) according to the Goutallier computed tomography classification, little is known about the morphometric verification of these findings. METHODS: The supraspinatus tendon was detached from the greater tubercle and the infraspinatus and subscapularis in 12 rabbits, and a 12-week observation period followed. This proved to be sufficient for development of grade >2 FD of the supraspinatus tendon. The tendon was then reinserted. The animals were euthanized 24 weeks after tendon reconstruction. The sections of middle part of supraspinatus were stained for adenosine triphosphatase reaction, and morphometric measurements were taken of type I and II muscle fiber diameters. The contralateral shoulders served as controls. RESULTS: The macroscopic inspection of the supraspinatus tendons revealed complete healing in all cases. No statistically significant differences were found between controls and operated-on shoulders for type I (P = .13) and type II (P = .55) muscle fibers. CONCLUSIONS: Atrophy of type I and II muscle fibers in rabbit supraspinatus muscle, characterized by grade >2 fatty degeneration according to the Goutallier computed tomography classification, is reversible after 24 weeks from reattachment of its tendon. A requirement for type I and II muscle fibers hypertrophy is a change in the biomechanical and functional conditions of the muscle after its tendon is reconstructed.

The effect of metallothionein 2A core promoter region single-nucleotide polymorphism on accumulation of toxic metals in sinonasal inverted papilloma tissues.

Metallothioneins (MTs) are intracellular thiol-rich heavy metal-binding proteins which join trace metal ions protecting cells against heavy metal toxicity and regulate metal distribution and donation to various enzymes and transcription factors. The goal of this study was to identify the -5 A/G (rs28366003) single-nucleotide polymorphism (SNP) in the core promoter region of the MT2A gene, and to investigate its effect on allele-specific gene expression and Cd, Zn, Cu and Ni content in sinonasal inverted papilloma tissue (IP), with non-cancerous sinonasal mucosa (NCM) as a control. The MT2A promoter region -5 A/G SNP was identified by restriction fragment length polymorphism using 117 IP and 132 NCM. MT2A gene analysis was performed by quantitative real-time PCR. Metal levels were analyzed by flame atomic absorption spectrometry. The frequency of A allele carriage was 99.2% and 100% in IP and NCM, respectively. The G allele carriage was detected in 23.9% of IP and in 12.1% of the NCM samples. As a result, a significant association of -5 A/G SNP in MT2A gene with mRNA expression in both groups was determined. A significant association was identified between the -5 A/G SNP in the MT2A gene with mRNA expression in both groups. A highly significant association was detected between the rs28366003 genotype and Cd and Zn content in IP. Furthermore, significant differences were identified between A/A and A/G genotype with regard to the type of metal contaminant. The Spearman rank correlation results showed the MT2A gene expression and both Cd and Cu levels were negatively correlated. The results obtained in this study suggest that the -5 A/G SNP in the MT2A gene may have an effect on allele-specific gene expression and toxic metal accumulation in sinonasal inverted papilloma.

Metallothionein 2A core promoter region genetic polymorphism and its impact on the risk, tumor behavior, and recurrences of sinonasal inverted papilloma (Schneiderian papilloma).

Inverted papillomas are a unique group of locally aggressive benign epithelial neoplasms in the nasal cavity and paranasal sinuses arising from the Schneiderian mucosa. Metallothioneins are sulfhydryl-rich heavy metal-binding proteins required for metal toxicity protection and regulation of biological mechanisms including proliferation and invasion. The goal of this study was to identify three SNPs at loci -5 A/G (rs28366003) and -209 A/G (rs1610216) in the core promoter region and at locus +838 C/G (rs10636) in 3'UTR region of the MT2A gene with IP risk and with tumor invasiveness according to Krouse staging. Genotyping was performed using the PCR restriction fragment length polymorphism technique in 130 genetically unrelated IP individuals, and 418 randomly selected healthy volunteers. The presence of the rs28366003 SNP was significantly related to the risk of IP within the present population-based case-control study. Compared to homozygous common allele carriers, heterozygosity and homozygosity for the G variant had a significantly increased risk of IP (adjusted odds ratio [OR] = 7.71, 95% confidence interval [CI]: 4.01-14.91, p(dominant) < 0.001). Moreover, risk allele carriers demonstrated higher Krouse stage (pT1 vs. pT2-4) (OR = 19.32; 95% CI, 2.30-173.53; p < 0.0001), diffuse tumor growth (OR = 4.58; 95% CI, 1.70-12.11; p = 0.0008), bone destruction (OR = 4.13; 95% CI, 1.50-11.60; p = 0.003), and higher incidence of tumor recurrences (OR = 5.11; 95% CI, 1.68-15.20; p = 0.001). The findings suggest that MT2A gene variation rs28366003 may be implicated in the etiology of sinonasal inverted papilloma in a Polish population.

Tissue Factor in Dermatitis Herpetiformis and Bullous Pemphigoid: Link between Immune and Coagulation System in Subepidermal Autoimmune Bullous Diseases.

Dermatitis herpetiformis (DH) and bullous pemphigoid (BP) are skin diseases associated with eosinophilic and neutrophilic infiltrations. Although chemokines are critical for the selective accumulation and activation of various leukocyte subsets in the inflammatory process, there are few findings concerning inflammatory cells and production of coagulation factors in blistering diseases. Skin biopsies were taken from 14 patients with DH, 27 with BP, and 20 control subjects. The localization and expression of tissue factor (TF) in skin lesions and perilesional skin were studied by immunohistochemistry and confirmed by Western Blot. Moreover the plasma concentrations of TF were measured by immunoassays. D dimers, fibrinogen, and selected coagulation parameters were measured by routine methods. Expression of TF in the epidermis and in inflammatory influxed cells in dermis was detected in skin biopsies from BP patients. Examined TF expression was detected in perilesional skin of all BP patients too. The expression of TF was not observed in biopsies from healthy people and DH patients. The findings of the study show an increased expression of tissue factor in the lesional and perilesional skin of patients with bullous pemphigoid. The difference in chemokine pattern expression and variations in the cellular infiltration in BP and DH cause variable expression of TF.

Spectrum of biopsy-proven renal diseases in patients with type 2 diabetes mellitus. A single center study.

This is the first report from Poland documenting biopsy-proven renal diseases in type 2 diabetes mellitus. We analyzed the data of 76 patients with type 2 diabetes who underwent renal biopsy and were diagnosed in the Department of Nephropathology, Medical University of Lodz. The patients were divided into the following three groups according to the histological diagnosis: group I - isolated non-diabetic renal disease (NDRD); group II - NDRD superimposed on underlying diabetic nephropathy (NDRD + DN); and group III - isolated diabetic nephropathy (DN). Non-diabetic renal disease was found in 38 patients (50%), non-diabetic renal disease superimposed on underlying diabetic nephropathy was diagnosed in 11 patients (14.5%), and isolated diabetic nephropathy was seen in 27 patients (35.5%). The most common glomerular lesion found in groups I and II was focal segmental glomerulosclerosis (FSGS). On the basis of clinical and laboratory parameters, differentiating NDRD from DN in diabetic patients is not always obvious. However, our study revealed that hematuria, short duration of diabetes and the absence of diabetic retinopathy in type 2 diabetic patients manifesting renal involvement may suggest NDRD. The only way to distinguish NDRD from DN is histological evaluation of renal tissue.

Augmented immunoexpression of survivin correlates with parameters of aggressiveness in prostate cancer.

The clinical significance of the immunoexpression of survivin in prostate cancer and its correlation with the biological aggressiveness of prostate cancer remains unclear. Therefore, the present study was undertaken to compare the immunoexpression of survivin in prostate cancer (PCa) and benign prostatic hyperplasia (BPH) as well as to determine whether this immunoexpression could correlate with Gleason score, proliferation activity and prostate specific antigen (PSA) levels. The prostate needle biopsies from 28 patients with elevated serum PSA levels were studied. As a control, 12 needle biopsies of prostate diagnosed as BPH were used. The immunoexpression of survivin was evaluated semiquantitatively, whereas the Ki-67 index was assessed quantitatively. The immunoexpression of survivin and Ki-67 in epithelial cells in the prostate cancer group was significantly increased as compared to BPH cases. In the prostate cancer group there were positive significant correlations between the immunoexpression of survivin and Gleason score as well as Ki­67 antigen. The correlation between the immunoexpression of survivin and PSA levels was also positive, but it did not reach statistical significance. In conclusion, we can confirm that in prostate cancer the immunoexpression of survivin is augmented as compared to BPH and positively correlated with parameters of tumor aggressiveness.