Expression of Beta-Catenin, Cadherins and P-Runx2 in Fibro-Osseous Lesions of the Jaw: Tissue Microarray Study.

Fibrous dysplasia (FD) and hyperparathyroidism-jaw tumor syndrome (HPT-JT) are well-characterized benign bone fibro-osseous lesions. The intracellular mechanism leading to excessive deposition of fibrous tissue and alteration of differentiation processes leading to osteomalacia have not yet been fully clarified. Tissue Microarray (TMA)-based immunohistochemical expression of ß-catenin, CK-AE1/AE3, Ki-67, cadherins and P-Runx2 were analyzed in archival samples from nine patients affected by FD and HPT-JT and in seven controls, with the aim of elucidating the contribution of these molecules (ß-catenin, cadherins and P-Runx2) in the osteoblast differentiation pathway. ß-catenin was strongly upregulated in FD, showing a hyper-cellulated pattern, while it was faintly expressed in bone tumors associated with HPT-JT. Furthermore, the loss of expression of OB-cadherin in osteoblast lineage in FD was accompanied by N-cadherin and P-cadherin upregulation (p < 0.05), while E-cadherin showed a minor role in these pathological processes. P-Runx2 showed over-expression in six out of eight cases of FD and stained moderately positive in the rimming lining osteoblasts in HPT-JT syndrome. ß-catenin plays a central role in fibrous tissue proliferation and accompanies the lack of differentiation of osteoblast precursors in mature osteoblasts in FD. The study showed that the combined evaluation of the histological characteristics and the histochemical and immunohistochemical profile of key molecules involved in osteoblast differentiation are useful in the diagnosis, classification and therapeutic management of fibrous-osseous lesions.

Protein corona profile of graphene oxide allows detection of glioblastoma multiforme using a simple one-dimensional gel electrophoresis technique: a proof-of-concept study.

Glioblastoma multiforme (GBM) is the most aggressive form of gliomas. The development of supplementary approaches for glioblastoma diagnosis, limited to imaging techniques and tissue biopsies so far, is a necessity of clinical relevance. In this context, nanotechnology might afford tools to enable early diagnosis. Upon exposure to biological media, nanoparticles are coated with a layer of proteins, the protein corona (PC), whose composition is individual and personalized. Here we show that the PC of graphene oxide nanosheets has a capacity to detect GBM using a simple one-dimensional gel electrophoresis technique. In a range of molecular weights between 100 and 120 kDa, the personalized PC from GBM patients is completely discernible from that of healthy donors and that of cancer patients affected by pancreatic adenocarcinoma and colorectal cancer. Using tandem mass spectrometry, we found that inter-alpha-trypsin inhibitor (ITI) heavy chain H4 is enriched in the PC of all tested individuals but not in the GBM patients. Overall, if confirmed on a larger cohort series, this approach could be advantageous at the first level of investigation to decide whether to carry out more invasive analyses and/or to follow up patients after surgery and/or pharmacological treatment.

Sex Hormones and Inflammation Role in Oral Cancer Progression: A Molecular and Biological Point of View.

Oral cancers have been proven to arise from precursors lesions and to be related to risk behaviour such as alcohol consumption and smoke. However, the present paper focuses on the role of chronic inflammation, related to chronical oral infections and/or altered immune responses occurring during dysimmune and autoimmune diseases, in the oral cancerogenesis. Particularly, oral candidiasis and periodontal diseases introduce a vicious circle of nonhealing and perpetuation of the inflammatory processes, thus leading toward cancer occurrence via local and systemic inflammatory modulators and via genetic and epigenetic factors.

Expression and clinical implication of cyclooxygenase-2 and E-cadherin in oral squamous cell carcinomas.

Epithelial-Mesenchymal Transition (EMT) and angiogenesis are crucial events for development of aggressive and often fatal Oral Squamous Cell Carcinomas (OSCCs). Both promote cancer progression and metastasis development, but while the former induces the loss of E-cadherin expression and, hence cadherin switching; the latter produces hematic blood vessel neo-formation and contribute to OSCC cell growth, tumor mass development, and dissemination. Cyclooxygenase-2 (COX-2) has an important role, not only in angiogenic mechanisms, but also in favoring cancer invasion. Indeed it decreases the expression of E-cadherin and leads to phenotypic changes in epithelial cells (EMT) enhancing their carcinogenic potential. Our aim is to evaluate the interplay between E-cadherin cytoplasmic delocalization, COX-2 up-regulation and COX-2 induced neo-angiogenesis in 120 cases of OSCC. We have analyzed the distribution and the number of neo-formed endothelial buds surrounding infiltrating cells that express COX-2, as well as the neo-formed vessels in chronic inflammatory infiltrate, which surround the tumor. A double immunostaining method was employed in order to verify co-localization of endothelial cell marker (CD34) and COX-2. IHC has also been used to assess E-cadherin expression. Our data demonstrate that the OSCC cells, which lose membranous E-cadherin staining, acquiring a cytoplasmic delocalization, overexpress COX-2. Moreover, we find a new CD34+ vessel formation (sprouting angiogenesis). Only basaloid type of OSCC showes low level of COX-2 expression together with very low level of neo-angiogenesis and consequent tumor necrosis. The well-known anti-metastatic effect of certain COX-2 inhibitors suggests that these molecules might have clinical utility in the management of advanced cancers.

Emerging role of secreted miR-210-3p as potential biomarker for clear cell Renal Cell Carcinoma metastasis.

BACKGROUND: MicroRNAs (miRNAs) are emerging as promising molecules in the diagnosis, prognosis and treatment of urological tumours. Recently, our group performed two independent studies highlighting that miR-210-3p may be a useful biomarker not only for diagnosis but also for post-surgery clear cell Renal Cell Carcinoma (ccRCC) management. OBJECTIVE: The aim of this study is to further explore the effectiveness of miRNA as non-invasive biomarker for clinical outcomes and ccRCC response to the treatment. METHODS: We analyzed miR-210-3p levels in neoplastic and healthy tissue and in urine specimens collected at surgery and during follow-up of 21 ccRCC patients by RTqPCR. RESULTS: Firstly, we confirmed that the expression of miR-210-3p was upregulated in tumor tissues and in urine samples of analyzed cohort. Of note is that miR-210-3p expression was significantly reduced in urine samples from disease-free patients during follow-up (from 3 to 12 months) compared to the baseline levels observed at the time of surgery. In a small subgroup of patients presenting metastatic progression (such as bone, intestinal or lung metastasis), the urine levels of miR-210-3p correlated with responsiveness to the therapy. CONCLUSIONS: This pilot study highlights the relevance of secreted miR-210-3p as powerful non-invasive prognostic and predictive biomarker for the evaluation of clinical outcomes and treatment response during ccRCC follow up.

The enigmatic role of matrix metalloproteinases in epithelial-to-mesenchymal transition of oral squamous cell carcinoma: Implications and nutraceutical aspects.

The most prevalent malignancy in the oral cavity is represented by oral squamous cell carcinoma, an aggressive disease mostly detected in low-income communities. This neoplasia is mostly diffused in older men particularly exposed to risk factors such as tobacco, alcohol, and a diet rich in fatty foods and poor in vegetables. In oral squamous cell carcinoma, a wide range of matrix-cleaving proteinases are involved in extracellular matrix remodeling of cancer microenvironment. In particular, matrix metalloproteinases (MMPs) represent the major and most investigated protagonists. Owing to their strong involvement in malignant pathologies, MMPs are considered the most promising new biomarkers in cancer diagnosis and prognosis. The interest in studying MMPs in oral cancer biology is also owing to their prominent role in epithelial-to-mesenchymal transition (EMT). EMT is an intricate process involving different complex pathways. EMT-related proteins are attractive diagnostic biomarkers that characterize the activation of biological events that promote cancer's aggressive expansion. Different antioncogenic natural compounds have been investigated to counteract oral carcinogenesis, with the scope of obtaining better clinical results and lower morbidity. In particular, we describe the role of different nutraceuticals used for the regulation of MMP-related invasion and proliferation of oral cancer cells.

Nanoparticle-biomolecular corona: A new approach for the early detection of non-small-cell lung cancer.

Lung cancer (LC) is the most common type of cancer and the second cause of death worldwide in men and women after cardiovascular diseases. Non-small-cell lung cancer (NSCLC) is the most frequent type of LC occurring in 85% of cases. Developing new methods for early detection of NSCLC could substantially increase the chances of survival and, therefore, is an urgent task for current research. Nowadays, explosion in nanotechnology offers unprecedented opportunities for therapeutics and diagnosis applications. In this context, exploiting the bio-nano-interactions between nanoparticles (NPs) and biological fluids is an emerging field of research. Upon contact with biofluids, NPs are covered by a biomolecular coating referred to as "biomolecular corona" (BC). In this study, we exploited BC for discriminating between NSCLC patients and healthy volunteers. Blood samples from 10 NSCLC patients and 5 subjects without malignancy were allowed to interact with negatively charged lipid NPs, leading to the formation of a BC at the NP surface. After isolation, BCs were characterized by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). We found that the BCs of NSCLC patients was significantly different from that of healthy individuals. Statistical analysis of SDS-PAGE results allowed discriminating between NSCLC cancer patients and healthy subjects with 80% specificity, 80% sensitivity and a total discriminate correctness rate of 80%. While the results of the present investigation cannot be conclusive due to the small size of the data set, we have shown that exploitation of the BC is a promising approach for the early diagnosis of NSCLC.

Prep1 Deficiency Affects Olfactory Perception and Feeding Behavior by Impairing BDNF-TrkB Mediated Neurotrophic Signaling.

Prep1 is a homeodomain transcription factor which has an important role in hindbrain development. Prep1 expression is also kept in adult mouse brain and in particular within the olfactory bulbs. Moreover, many Prep1 neurons co-localize with Calbindin-positive periglomerular interneurons in olfactory glomerular layer. However, Prep1 function in this brain region is still unknown. In this study, we show that Prep1 hypomorphic heterozygous (Prep1i/+) mice express low levels of protein and feature a 30% reduction of olfactory bulb area, compared to WT mice. In addition, Prep1i/+ mice olfactory bulb histological analysis indicated a 20% lower cytochrome C oxidase activity within the glomerular layer, accompanied by a reduced number of periglomerular interneurons, compared to the WT littermates. Consistently, olfactory perception test highlighted that Prep1 hypomorphic heterozygous mice display a scant ability to distinguish odors, which significantly impacts on feeding behavior, as Prep1i/+ mice revealed a reduced preference for high-fat food. Analysis of BDNF signaling, which represents the main molecular mediator of olfactory plasticity, showed that Prep1i/+ mouse olfactory bulbs feature a 30% reduction of TrkB receptor levels and a decreased activation of ERK1/2. Similarly, overexpression of Prep1 in mouse neuronal cells (N2A) caused an increase of TrkB expression levels, BDNF-induced ERK phosphorylation, and cell viability, compared to control cells. We conclude that Prep1 deficiency alters olfactory morpho-functional integrity and olfaction-mediated eating behavior by affecting BDNF-TrkB signaling. Prep1 could, therefore, play a crucial role in behavioral dysfunctions associated to impaired responsiveness to BDNF.

Secreted miR-210-3p as non-invasive biomarker in clear cell renal cell carcinoma.

The most common subtype of renal cell carcinoma (RCC) is clear cell RCC (ccRCC). It accounts for 70-80% of all renal malignancies representing the third most common urological cancer after prostate and bladder cancer. The identification of non-invasive biomarkers for the diagnosis and responsiveness to therapy of ccRCC may represent a relevant step-forward in ccRCC management. The aim of this study is to evaluate whether specific miRNAs deregulated in ccRCC tissues present altered levels also in urine specimens. To this end we first assessed that miR-21-5p, miR-210-3p and miR-221-3p resulted upregulated in ccRCC fresh frozen tissues compared to matched normal counterparts. Next, we evidenced that miR-210-3p resulted significantly up-regulated in 38 urine specimens collected from two independent cohorts of ccRCC patients at the time of surgery compared to healthy donors samples. Of note, miR-210-3p levels resulted significantly reduced in follow-up samples. These results point to miR-210-3p as a potential non-invasive biomarker useful not only for diagnosis but also for the assessment of complete resection or response to treatment in ccRCC management.

Multifaceted Breast Cancer: The Molecular Connection With Obesity.

Obesity is characterized by a disruption in energy balance regulation that results in an excess accumulation of body fat. Its increasing prevalence poses a major public health concern because it is a risk factor for a host of additional chronic conditions, including type 2 diabetes, hypertension, and cardiovascular disease. Obesity is increasingly recognized as a growing cause of cancer risk. In particular excessive adipose expansion during obesity causes adipose dysfunction and inflammation that can regulate tumor growth. In obesity, dysregulated systemic metabolism and inflammation induce hyperinsulinemia, hyperglycemia, dyslipidemia, and enhance sex hormone production with increased secretion of proinflammatory adipokine that impact breast cancer development and progression. This review describes how adipose inflammation that characterizes obesity is responsible of microenvironment to promote cancer, and discuss how steroid hormones, that are essential for the maintenance of the normal development, growth and differentiation of the cells, influence the induction and progression of breast cancer. J. Cell. Physiol. 232: 69-77, 2017. © 2016 Wiley Periodicals, Inc.

Evaluation of matrix metalloproteinase type IV-collagenases in serum of patients with tumors of the central nervous system.

The basement membrane collagen IV-degrading matrix metalloproteinases -2 and -9 (MMPs) are most often linked to the malignant phenotype of tumor cells by playing a critical role in invasion, metastasis, angiogenesis, and vasculogenesis. We verified the activity of these two MMPs in the sera of patients affected by brain tumors (20 gliomas, 28 meningiomas and 20 metastasis) by zymography. The sera of 25 healthy volunteers with no concomitant illnesses were used for controls. Zymography showed four dominant gelatinolytic bands of 240, 130, 92 (MMP-9) and 72 (MMP-2) kDa. No statistically significant variations of MMP-2 proteolytic activity between patients and healthy individuals were observed. On the contrary, MMP-9 (both monomeric and multimeric forms) lytic activities were significantly higher in tumors specimens compared to healthy controls (p < 0.001). Moreover, MMP-9 immunohistochemistry revealed: (1) a strong reactivity in neoplastic vessels of high-grade gliomas showing an inverse correlation with serum multimeric gelatinolytic activity; (2) a cytoplasmatic reactivity in meningiomas with a significantly increase in atypical meningioma compared with low-grade ones (p = 0.036); (3) a positive correlation between MMP-9 and Ki-67 (Sperman Rho coefficient r = 0.418 and p = 0.034). Our results suggest that serum and tissue MMP-9 might provide clinicians additional objective information in intracranial neoplasms. Finally, it should be possible to use MMP-9 as a target for new forms of therapy. Nevertheless, due to the small number of patients included in the study, the conclusion may not be transferable to the general population and therefore further evaluations are needed.

Malvidin's Effects on Rat Pial Microvascular Permeability Changes Due to Hypoperfusion and Reperfusion Injury.

The present study was aimed to evaluate the malvidin's protective effects on damage induced by 30 min bilateral common carotid artery occlusion (BCCAO) and 60 min reperfusion (RE) in rat pial microcirculation. Rat pial microcirculation was observed using fluorescence microscopy through a closed cranial window. Western blotting analysis was performed to investigate the endothelial nitric oxide synthase (eNOS), phosphorylated eNOS (p-eNOS) and matrix metalloproteinase 9 (MMP-9) expression. Moreover, MMP-9 activity was evaluated by zymography. Finally, neuronal damage and radical oxygen species (ROS) formation were assessed. In all animals, pial arterioles were classified in five orders of branching according to Strahler's method. In hypoperfused rats, 30 min BCCAO and 60 min RE caused a decrease in arteriolar diameter, an increase in microvascular leakage and leukocyte adhesion, accompanied by decreased capillary perfusion and red blood cell velocity (VRBC). Moreover, marked neuronal damage and evident ROS generation were detected. Conversely, malvidin administration induced arteriolar dilation in dose-related manner, reducing microvascular leakage as well as leukocyte adhesion. Capillary perfusion and VRBC were protected. Nitric oxide (NO) synthase inhibition significantly attenuated malvidin's effects on arteriolar diameter. Western blotting analysis revealed an increase in eNOS and p-eNOS expression, while zymography indicated a decrease in MMP-9 activity after malvidin's administration. Furthermore, malvidin was able to prevent neuronal damage and to decrease ROS generation. In conclusion, malvidin protects rat pial microcirculation against BCCAO/RE injury, preventing blood-brain impairment and neuronal loss. Malvidin's effects appear to be mediated by eNOS activation and scavenger activity.

Matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in diagnosis of pleural effusion of malignant origin.

OBJECTIVES: The aim of the present study was to evaluate the diagnostic accuracy of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in differentiating benign from malignant exudative pleural effusions. METHODS: This is a unicentre observational study including 97 consecutive patients with exudative pleural effusions. Metalloproteinase-9, tissue inhibitor of metalloproteinase-1, lactate dehydrogenase, ferritin, carcinoembryonic antigen and carbohydrate antigen 15-3 were measured in pleural effusion and serum by enzyme-linked immunosorbent assay. The activity of metalloproteinase-9 was also evaluated by substrate zymography. The data were correlated with final diagnosis of pleural effusions to evaluate the diagnostic accuracy. RESULTS: Of the 97 eligible patients, 6 were excluded. Of the 91 patients included in the study, 70 had malignant pleural effusions and 21 had benign pleural effusions. Both in sera and pleural effusions, matrix metalloproteinase-9 (P < 0.0001), tissue inhibitor of metalloproteinase-1 (P < 0.0001) and carcinoembryonic antigen (P < 0.0001) levels were higher in neoplastic patients than in benign group. Zymography analysis showed a most prominent band at a molecular weight of 92 kDa (metalloproteinase-9) whereas a less intense band was observed at 72 kDa (metalloproteinase-2). A significant correlation was found between metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 levels in pleural effusion (P < 0.0001; r = 0.8) and serum (P < 0.03; r = 0.2). Pleural effusion metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 levels showed higher value of sensitivity (97 and 91%, respectively) and specificity (90 and 95%, respectively) compared with other standard markers. Serum metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 levels showed similar results. Among 70 neoplastic patients, 29 had negative pleural cytology. Of these, 25 presented elevated levels of metalloproteinase-9 and tissue inhibitor of metalloproteinase-1, whereas 4 patients had elevated levels of one of the two markers. CONCLUSIONS: Our results showed that metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 might be valuable markers in differentiating benign from malignant pleural effusions. Their levels are neither influenced by the histology and tumour origin nor by the presence of tumour cells in pleural effusions. Thus, their use in clinical practice could help in the selection of patients needing more invasive procedures, such as thoracoscopic biopsy.

Substrate-zymography: a still worthwhile method for gelatinases analysis in biological samples.

Matrix metallo-proteinases (MMPs) are a family of zinc-dependent endopeptidases, capable of degrading all the molecular components of extracellular matrix. A class of MMPs is gelatinases which includes gelatinase A or MMP-2 (72 kDa) and gelatinase B or MMP-9 (92 kDa), which have been shown to play critical roles in pathophysiology of many human disease and, in particular, cancer progression. For these reasons they obtained a great interest as potential non-invasive biomarker in providing useful clinical information in cancer diagnosis and therapy. A sensitive and unexpensive method for analysis of gelatinases is the gelatine zymography, which allows to measure the relative amounts of active and inactive enzymes in body fluids and tissue extracts. The procedure involves the electrophoretic separation of proteins under denaturing but non reducing conditions through a polyacrylamide gel containing a synthetic substrate (gelatin). The aim of this mini-review has been to describe the general principles of gelatine zymography technique, underling the main advantages and disadvantages. Even though an improvement of this method is necessary for a better applicability in laboratory medicine, gelatine zymography represents the most convenient method to detect the activity of the different gelatinases from a wide range of biological samples.

Translational Research and Plasma Proteomic in Cancer.

Proteomics is a recent field of research in molecular biology that can help in the fight against cancer through the search for biomarkers that can detect this disease in the early stages of its development. Proteomic is a speedily growing technology, also thanks to the development of even more sensitive and fast mass spectrometry analysis. Although this technique is the most widespread for the discovery of new cancer biomarkers, it still suffers of a poor sensitivity and insufficient reproducibility, essentially due to the tumor heterogeneity. Common technical shortcomings include limitations in the sensitivity of detecting low abundant biomarkers and possible systematic biases in the observed data. Current research attempts are trying to develop high-resolution proteomic instrumentation for high-throughput monitoring of protein changes that occur in cancer. In this review, we describe the basic features of the proteomic tools which have proven to be useful in cancer research, showing their advantages and disadvantages. The application of these proteomic tools could provide early biomarkers detection in various cancer types and could improve the understanding the mechanisms of tumor growth and dissemination.

Evaluation of MMP-2, MMP-9, TIMP-1, TIMP-2, NGAL and MMP-9/NGAL complex in urine and sera from patients with bladder cancer.

The identification of biomarkers in urine or serum samples from patients with bladder cancer is urgently required for the development of non-invasive methods for the diagnosis of bladder carcinoma and to facilitate follow-up surveillance, to combat the high progression and recurrence rates of this type of cancer. The current study measured the content of matrix metalloproteinase (MMP)-2 and -9, as well as tissue inhibitor of metalloproteinase (TIMP)-1 and -2 in the urine and sera of 41 patients with bladder cancer by ELISA. The association between levels of MMP-2 and -9 and TIMP-1 and -2, and tumor grade and stage were investigated to verify whether these molecules are involved in tumor differentiation. Statistical analysis of the data revealed that urinary TIMP-1 levels were significantly higher in the high grade group compared with those of the low grade samples (P=0.022). The results also revealed a significantly differing distribution of TIMP-1 expression between Ta and T1 stage specimens (P=0.040). The corresponding area under the curves (AUCs) were 0.72, with a sensitivity of 0.70 and specificity of 0.75. In addition, neutrophil gelatinase-associated lipocalin (NGAL) and MMP-9/NGAL complex levels in the sera were measured. All molecules evaluated were detected in the sera of the patients studied. In particular, tumors staged as non-muscle invasive (Ta and T1), demonstrated significantly higher NGAL levels compared with those of muscle invasive (>T1) bladder cancer (32.8 ng/ml vs. 16.2 ng/ml; P=0.029). The discriminatory ability of NGAL expression was confirmed by receiver operating characteristic curve analysis that revealed an AUC of 0.75, a sensitivity of 0.88 and a specificity of 0.67. These data indicated that urinary TIMP-1 and serum NGAL may be useful non-invasive biomarkers to provide clinical information for bladder cancer disease management. Multicenter, prospective studies are required to confirm these preliminary results.

Oncogenic MicroRNAs Characterization in Clear Cell Renal Cell Carcinoma.

A key challenge for the improvement of clear cell renal cell carcinoma (ccRCC) management could derive from a deeper characterization of the biology of these neoplasms that could greatly improve the diagnosis, prognosis and treatment choice. The aim of this study was to identify specific miRNAs that are deregulated in tumor vs. normal kidney tissues and that could impact on the biology of ccRCC. To this end we selected four miRNAs (miR-21-5p, miR-210-3p, miR-185-5p and miR-221-3p) and their expression has been evaluated in a retrospective cohort of formalin-fixed paraffin-embedded (FFPE) tissues from 20 ccRCC patients who underwent surgical nephrectomy resection. miR-21-5p and miR-210-3p resulted the most significantly up-regulated miRNAs in this patient cohort, highlighting these onco-miRNAs as possible relevant players involved in ccRCC tumorigenesis. Thus, this study reports the identification of specific oncogenic miRNAs that are altered in ccRCC tissues and suggests that they might be useful biomarkers in ccRCC management.

Molecular profile of sensitization in subjects with short occupational exposure to latex.

OBJECTIVES: We examined the prevalence of latex allergy in subjects with occupational exposure to latex allergens for less than 5 years, determining the disease spectrum in symptomatic workers. We identified the most frequent molecular allergens by Immuno- CAP (ICAP), correlating the findings with skin prick test (SPT) results. MATERIAL AND METHODS: Seven hundred twenty-three healthcare students using latex gloves on a regular basis were invited to participate in a baseline questionnaire screening. An ICAP serum test was performed only when a possible latex allergy was indicated by the questionnaire. RESULTS: The total number of participants responding to the baseline survey was 619. Glove-related symptoms were indicated by 4% (N = 25) of the students. The most common symptom was contact dermatitis (N = 18, 72%). In 12 subjects, ICAP revealed a real sensitization to latex, with a recombinant latex allergen profile showing a high frequency for rHev b 6.01 specific immunoglobulin E (sIgE) (N = 9, 67%). In these individuals, skin symptoms were more prevalent than other types (88%). CONCLUSIONS: The combined positivity for rHev b 6.01, rHev 8 and rHev b 5 determined by ICAP identified 92% of latex-allergic subjects with short-term exposure to latex.

Matrix metalloproteinase-2 and -9 and tissue inhibitor of metalloproteinase-1 and -2 in sera and urine of patients with renal carcinoma.

The matrix metalloproteinase (MMP) family has been shown to play a critical role in tissue remodeling and tumor infiltration. Their activity is normally strictly controlled by tissue inhibitors of metalloproteinases (TIMPs). However, TIMPs act indirectly through modulation of protease activity or directly through cell surface receptors to direct cell fate. These molecules have been proposed as markers of malignant cancer. Previous studies on MMP and TIMP expression in kidney carcinoma have been limited and have reported variable observations. The current study measured the content of MMP-2 and -9 and TIMP-1 and -2 in the sera and urine of patients with kidney carcinoma by enzyme-linked immunosorbent assay. Of these patients, 16 exhibited clear cell renal cell carcinoma (ccRCC) and 4 exhibited oncocytoma. Sera and urine samples of 53 healthy subjects were used as controls. In the sera of the control group, MMP-2 and TIMP-2 were detectable in all samples, while MMP-9 and TIMP-1 were below the sensitivity of the assay. In the pathological specimens, the mean serum values of MMP-2 and TIMP-1 and -2 were similar in the ccRCC and oncocytoma patients, whereas the value for MMP-9 was 2-fold higher in the ccRCC patients compared with the oncocytoma patients. With regard to the urine specimens, all four molecules were undetectable in the normal healthy samples and in a few pathological samples. The mean values for MMP-2 and -9 and TIMP-2 in the positive urine specimens were similar in the ccRCC and oncocytoma patients, whereas the mean value of TIMP-1 was higher in the ccRCC patients compared with that of the oncocytoma patients. The mean urinary levels of the four molecules were less than those of the sera. Statistical analysis of the data did not reveal any correlation between the tumor grades and expression levels of the molecules examined.

Evaluation of neutrophil gelatinase-associated lipocalin (NGAL), matrix metalloproteinase-9 (MMP-9) and their complex MMP-9/NGAL in sera and urine of patients with kidney tumors.

Recent evidence suggests that neutrophil gelatinase-associated lipocalin (NGAL) is required for the development and/or progression of benign and malignant disease, and is overexpressed in several types of tumor. Matrix metalloproteinase-9 (MMP-9), by degrading components of the extracellular matrix and thus promoting the release of growth factors, is important in tumor growth and tumorigenicity. NGAL protects MMP-9 from proteolytic degradation and enhances its enzymatic activities by binding and forming the MMP-9/NGAL complex. Therefore, NGAL, MMP-9 and their complex MMP-9/NGAL have been proposed as soluble biomarkers for numerous malignancies. In the present study, we measured the concentration of these molecules in sera and urine of patients with kidney disease using ELISA. Of these patients, 16 had clear cell renal cell carcinoma (ccRCC) and 4 had oncocytoma. Sera and urine samples of 53 healthy patients were used as controls. In sera, MMP-9 was enhanced in ccRCC patients compared with oncocytoma patients. In urine, the most abundant molecule was NGAL and its mean value was higher in cancer patients. However, there was a broad overlap of the data and we did not identify any correlation with disease type, stage or grade. Therefore, these molecules may not be useful as biomarkers for predicting kidney carcinoma.