Immune expression of E-cadherin and alpha, beta and gamma-Catenin adhesion molecules and prognosis for upper urinary tract urothelial carcinomas

Introduction: Cell adhesion molecules (CAM) are required for maintaining a normal epithelial phenotype, and abnormalities in CAM expression have been related to cancer progression, including bladder urothelial carcinomas. There is only one study that correlates E-cadherin and alpha-, beta- and gamma-catenin expression with prognosis of upper tract urothelial carcinomas. Our aim is to study the pattern of immune expression of these CAMs in urothelial carcinomas from the renal pelvis and ureter in patients who have been treated surgically. Our goal is to correlate these expression levels and characteristics with well-known prognostic parameters for disease-free survival. Materials and Methods: We evaluated specimens from 20 patients with urothelial carcinomas of the renal pelvis and ureter who were treated with nephroureterectomy or ureterectomy between June 1997 and January 2007. CAM expression was evaluated by immunohistochemistry in a tissue microarray and correlated with histopathological characteristics and patient outcomes after a mean follow-up of 55 months. Results: We observed a relationship between E-cadherin expression and disease recurrence. Disease recurrence occurred in 87.5% of patients with strong E-cadherin expression. Only 50.0% of patients with moderate expression and 0% of patients with weak or no expression of E-cadherin had disease recurrence (p = 0.014). There was also a difference in disease-free survival. Patients with strong E-cadherin expression had a mean disease-free survival rate of 49.1 months, compared to 83.9 months for patients with moderate expression (p = 0.011). Additionally, an absence of a-catenin expression was associated with tumors that were larger than 3 cm (p = 0.003). Conclusions: We demonstrated for the first time that immune expression of E-cadherin is related to tumor recurrence and disease-free survival rates, and the absence of a-catenin expression is related to tumor size in upper tract urothelial carcinomas

Increased expression of MMP-9 and IL-8 are correlated with poor prognosis of Bladder Cancer

Background: Extracellular matrix homeostasis is strictly maintained by a coordinated balance between the expression of metalloproteinases (MMPs) and their inhibitors. The purpose of this study was to investigate whether the expression of MMP-9, MMP-2 and its specific inhibitors, are expressed in a reproducible, specific pattern and if the profiles are related to prognosis in Bladder Cancer (BC). Methods: MMP-9, MMP-2 and its specific inhibitors expression levels were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) in fresh-frozen malignant tissue collected from 40 patients with BC submitted to transurethral resection of bladder. The control group consisted of normal bladder tissue from five patients who had undergone retropubic prostatectomy to treat benign prostatic hyperplasia. Results: MMP-9 was overexpressed in 59.0 % of patients, and MMP-2, TIMP-1, TIMP-2, MMP-14, RECK and IL-8 was underexpressed in most of the patients. Regarding prognostic parameters we observed that high-grade tumors exhibited significantly higher levels of MMP-9 and IL-8 (p = 0.012, p = 0.003). Invasive tumors (pT1-pT2) had higher expression levels of MMP-9 than superficial tumors (pTa) (p = 0.026). The same was noted for IL-8 that was more expressed by invasive tumors (p = 0.015, p = 0.048). Most importantly tumor recurrence was related with higher levels of both MMP-9 (p = 0.003) and IL-8 (p = 0.005). Conclusion: We have demonstrated that the overexpression of MMP-9 and higher expression of IL-8 are related to unfavorable prognostic factors of urothelial bladder cancer and tumor recurrence and may be useful in the follow up of the patients.FAPESP (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo) [2009/50368-9]Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP

The role of micro RNAs 143 and 145 and their target genes in the etiopathogenesis of benign prostatic hyperplasia

Introdução: A hiperplasia prostática benigna (HPB) é apontada como um dos mais comuns problemas de saúde associado ao envelhecimento dos homens. A incidência da doença começa a aumentar a partir dos 40 anos de idade, e se torna frequente em cerca de 50% dos homens com 50 anos e em quase 90% dos homens após a oitava década. A etiopatogenia da HPB ainda não foi totalmente elucidada, mas sabe-se que alguns fatores aumentam os riscos de aparecimento do problema. Seu melhor entendimento contribuiria substancialmente para o estabelecimento de um consenso terapêutico para a doença. Nesse sentido, os marcadores moleculares têm sido pesquisados na tentativa de auxiliar ou mesmo suplantar a eficiência dos métodos tradicionais. MicroRNAs (miRNAs) são uma classe de pequenos RNA regulatórios (19-25 nucleotídeos), não codificadores que possuem um papel fundamental no controle da expressão gênica. Essas pequenas moléculas estão envolvidas em vários processos celulares fisiológicos e patológicos. Alguns estudos demonstraram que os miRNAs 143 e 145 têm papel fundamental na diferenciação e proliferação celular da musculatura lisa. A ação de miRNAs na HPB ainda foi pouco explorada. Objetivos: Analisar a expressão do miR-143 e de seus genes e proteínas alvo ERK5 e KRAS e do miR-145 e dos seus genes e proteínas alvo MAP3K3 e MAP4K4, em pacientes portadores de HPB e comparar os perfis de expressão destes com parâmetros clínicos dos pacientes. Material e Métodos: Para análise dos miRNAs e dos seus genes alvo, foram estudados 44 pacientes diagnosticados com HPB submetidos à ressecção transuretral da próstata ou prostatectomia aberta. A análise da expressão foi realizada pela técnica de RT-PCR quantitativo. O grupo controle foi composto de tecido prostático normal de dois pacientes jovens doadores de órgãos. A análise proteica foi feita a partir de 38 pacientes, pela técnica de Western Blotting. Resultados: Os miRNA 143 e 145, apresentaram superexpressão em 62,5% e 73,8% dos casos, respectivamente. O gene ERK5 apresentou subexpressão de 59,4%, evidenciando um possível controle negativo por parte do miR-143. O gene MAP4K4 apresentou subexpressão na totalidade das amostras estudadas, demonstrando um possível controle por parte do miR-145. Os genes KRAS e MAP3K3 apresentaram superexpressão de 79,4% e 61,5% das amostras, respectivamente. De acordo com a expressão proteica, encontramos perfis semelhantes aos da expressão gênica. Foi encontrada maior expressão das proteínas KRAS e MAP3K3. Considerando a expressão gênica e proteica comparadas aos parâmetros clínicos, somente a proteína ERK5 apresentou significância (p=0,019), estando mais presente em pacientes com próstatas > 60 gramas. Conclusão: A superexpressão dos miRNAs 143 e 145 encontrada neste estudo pode estar envolvida na etiopatogenia da HPB alterando a homeostase do tecido fibromuscular principalmente, controlando proliferação e diferenciação. A superexpressão gênica e a forte expressão proteica de KRAS também pode estar envolvida na etiopatogenia da HPB, já que esta molécula quando ativada é responsável pelo estímulo de vias que resultam na proliferação, sobrevivência, motilidade celular e tráfego intracelular. A superexpressão do MAP3K3 pode estar sendo responsável pela angiogênese que ocorre em HPB. A subexpressão de MAP4K4, neste caso possivelmente controlada por miR-145, pode estar deixando de regular negativamente mTOR, gerando uma proliferação celular irregular responsável pela HPB. A detecção das proteínas em níveis semelhantes aos que foram encontrados na expressão gênica reforça estas hipóteses.Introduction: Benign prostatic hyperplasia (BPH) is one of the most common male health problems associated with aging. The incidence of disease starts to increase after 40 years, and compromises half of men in the fifths and almost 90% over 80 years. The pathogenesis of BPH has not been fully elucidated, but it is known that some factors increase the risk of occurrence of the problem. A better understanding of BPH pathogenesis would substantially contribute to the establishment of a therapeutic consensus for the disease. Thus, molecular markers have been investigated attempting to help or even overcome the efficiency of traditional methods. MicroRNAs (miRNAs) are a class of small non-coding regulatory RNA (19-25 nucleotides) that plays a key role in gene expression control. These small molecules are involved in various physiological and pathological cellular processes. Some studies have shown that miRNAs 143 and 145 play a fundamental role in cellular differentiation and proliferation of smooth muscles. The action of miRNAs in BPH has been poorly explored. Objectives: Analyze the expression of miR-143 and its target genes and proteins ERK5 and KRAS and miR-145 and its target genes and proteins MAP3K3 and MAP4K4, in patients with BPH and compare their expression profiles with clinical parameters of patients. Material and Methods: For analysis of miRNAs and its target genes, we studied 44 patients diagnosed with BPH undergoing transurethral resection of the prostate or open prostatectomy. The expression analysis was performed by quantitative RT-PCR. Control group consisted of normal prostate tissue from two young patients organ donors. Protein analysis was done from of 38 patients using Western Blotting technique. Results: miR-143 and 145 presented overexpression in 62.5% and 73.8% of cases, respectively. The ERK5 gene demonstrated underexpression in 59.4%, indicating a possible control by the miR-143. MAP4K4 gene showed underexpression in 100% of samples and could be under a potential control by the miR-145. KRAS and MAP3K3 genes revealed overexpression of 79.4% and 61.5% of cases, respectively. According protein expression, to find similar profiles of gene expression. We found an increased expression of the proteins MAP3K3 and KRAS. Considering the gene expression and protein compared to clinical parameters, only the protein ERK5 showed significance (p = 0.019), being more present in patients with prostates > 60 grams. Conclusions: Overexpression of miRNAs 143 and 145 found in this work may be involved in the pathogenesis of BPH mainly by changing the fibromuscular tissue homeostasis, controlling proliferation and differentiation. Overexpression of KRAS may also be involved in the pathogenesis of BPH, since this molecule when activated can trigger cell proliferation, survival, intracellular trafficking and motility. Overexpression of MAP3K3 can be responsible for BPH angiogenesis. The MAP4K4 underexpression, in this case possibly controlled by miR-145 overexpression, could inhibit mTOR pathway, leading to irregular cell proliferation responsible for disease. Detection of proteins at similar levels to those found in gene expression reinforce our hypothesis

The role of micro RNAs 143 and 145 and their target genes in the etiopathogenesis of benign prostatic hyperplasia

Introdução: A hiperplasia prostática benigna (HPB) é apontada como um dos mais comuns problemas de saúde associado ao envelhecimento dos homens. A incidência da doença começa a aumentar a partir dos 40 anos de idade, e se torna frequente em cerca de 50% dos homens com 50 anos e em quase 90% dos homens após a oitava década. A etiopatogenia da HPB ainda não foi totalmente elucidada, mas sabe-se que alguns fatores aumentam os riscos de aparecimento do problema. Seu melhor entendimento contribuiria substancialmente para o estabelecimento de um consenso terapêutico para a doença. Nesse sentido, os marcadores moleculares têm sido pesquisados na tentativa de auxiliar ou mesmo suplantar a eficiência dos métodos tradicionais. MicroRNAs (miRNAs) são uma classe de pequenos RNA regulatórios (19-25 nucleotídeos), não codificadores que possuem um papel fundamental no controle da expressão gênica. Essas pequenas moléculas estão envolvidas em vários processos celulares fisiológicos e patológicos. Alguns estudos demonstraram que os miRNAs 143 e 145 têm papel fundamental na diferenciação e proliferação celular da musculatura lisa. A ação de miRNAs na HPB ainda foi pouco explorada. Objetivos: Analisar a expressão do miR-143 e de seus genes e proteínas alvo ERK5 e KRAS e do miR-145 e dos seus genes e proteínas alvo MAP3K3 e MAP4K4, em pacientes portadores de HPB e comparar os perfis de expressão destes com parâmetros clínicos dos pacientes. Material e Métodos: Para análise dos miRNAs e dos seus genes alvo, foram estudados 44 pacientes diagnosticados com HPB submetidos à ressecção transuretral da próstata ou prostatectomia aberta. A análise da expressão foi realizada pela técnica de RT-PCR quantitativo. O grupo controle foi composto de tecido prostático normal de dois pacientes jovens doadores de órgãos. A análise proteica foi feita a partir de 38 pacientes, pela técnica de Western Blotting. Resultados: Os miRNA 143 e 145, apresentaram superexpressão em 62,5% e 73,8% dos casos, respectivamente. O gene ERK5 apresentou subexpressão de 59,4%, evidenciando um possível controle negativo por parte do miR-143. O gene MAP4K4 apresentou subexpressão na totalidade das amostras estudadas, demonstrando um possível controle por parte do miR-145. Os genes KRAS e MAP3K3 apresentaram superexpressão de 79,4% e 61,5% das amostras, respectivamente. De acordo com a expressão proteica, encontramos perfis semelhantes aos da expressão gênica. Foi encontrada maior expressão das proteínas KRAS e MAP3K3. Considerando a expressão gênica e proteica comparadas aos parâmetros clínicos, somente a proteína ERK5 apresentou significância (p=0,019), estando mais presente em pacientes com próstatas > 60 gramas. Conclusão: A superexpressão dos miRNAs 143 e 145 encontrada neste estudo pode estar envolvida na etiopatogenia da HPB alterando a homeostase do tecido fibromuscular principalmente, controlando proliferação e diferenciação. A superexpressão gênica e a forte expressão proteica de KRAS também pode estar envolvida na etiopatogenia da HPB, já que esta molécula quando ativada é responsável pelo estímulo de vias que resultam na proliferação, sobrevivência, motilidade celular e tráfego intracelular. A superexpressão do MAP3K3 pode estar sendo responsável pela angiogênese que ocorre em HPB. A subexpressão de MAP4K4, neste caso possivelmente controlada por miR-145, pode estar deixando de regular negativamente mTOR, gerando uma proliferação celular irregular responsável pela HPB. A detecção das proteínas em níveis semelhantes aos que foram encontrados na expressão gênica reforça estas hipóteses.Introduction: Benign prostatic hyperplasia (BPH) is one of the most common male health problems associated with aging. The incidence of disease starts to increase after 40 years, and compromises half of men in the fifths and almost 90% over 80 years. The pathogenesis of BPH has not been fully elucidated, but it is known that some factors increase the risk of occurrence of the problem. A better understanding of BPH pathogenesis would substantially contribute to the establishment of a therapeutic consensus for the disease. Thus, molecular markers have been investigated attempting to help or even overcome the efficiency of traditional methods. MicroRNAs (miRNAs) are a class of small non-coding regulatory RNA (19-25 nucleotides) that plays a key role in gene expression control. These small molecules are involved in various physiological and pathological cellular processes. Some studies have shown that miRNAs 143 and 145 play a fundamental role in cellular differentiation and proliferation of smooth muscles. The action of miRNAs in BPH has been poorly explored. Objectives: Analyze the expression of miR-143 and its target genes and proteins ERK5 and KRAS and miR-145 and its target genes and proteins MAP3K3 and MAP4K4, in patients with BPH and compare their expression profiles with clinical parameters of patients. Material and Methods: For analysis of miRNAs and its target genes, we studied 44 patients diagnosed with BPH undergoing transurethral resection of the prostate or open prostatectomy. The expression analysis was performed by quantitative RT-PCR. Control group consisted of normal prostate tissue from two young patients organ donors. Protein analysis was done from of 38 patients using Western Blotting technique. Results: miR-143 and 145 presented overexpression in 62.5% and 73.8% of cases, respectively. The ERK5 gene demonstrated underexpression in 59.4%, indicating a possible control by the miR-143. MAP4K4 gene showed underexpression in 100% of samples and could be under a potential control by the miR-145. KRAS and MAP3K3 genes revealed overexpression of 79.4% and 61.5% of cases, respectively. According protein expression, to find similar profiles of gene expression. We found an increased expression of the proteins MAP3K3 and KRAS. Considering the gene expression and protein compared to clinical parameters, only the protein ERK5 showed significance (p = 0.019), being more present in patients with prostates > 60 grams. Conclusions: Overexpression of miRNAs 143 and 145 found in this work may be involved in the pathogenesis of BPH mainly by changing the fibromuscular tissue homeostasis, controlling proliferation and differentiation. Overexpression of KRAS may also be involved in the pathogenesis of BPH, since this molecule when activated can trigger cell proliferation, survival, intracellular trafficking and motility. Overexpression of MAP3K3 can be responsible for BPH angiogenesis. The MAP4K4 underexpression, in this case possibly controlled by miR-145 overexpression, could inhibit mTOR pathway, leading to irregular cell proliferation responsible for disease. Detection of proteins at similar levels to those found in gene expression reinforce our hypothesis

Immune expression of E-cadherin and α, β and γ-Catenin adhesion molecules and prognosis for upper urinary tract urothelial carcinomas

ABSTRAcT ARTIcLE INFO _________________________________________________________ ___________________ Introduction: Cell adhesion molecules (CAM) are required for maintaining a normal epithelial phenotype, and abnormalities in CAM expression have been related to cancer progression, including bladder urothelial carcinomas. There is only one study that correlates E-cadherin and α-, β-and γ-catenin expression with prognosis of upper tract urothelial carcinomas. Our aim is to study the pattern of immune expression of these CAMs in urothelial carcinomas from the renal pelvis and ureter in patients who have been treated surgically. Our goal is to correlate these expression levels and characteristics with well-known prognostic parameters for disease-free survival. Materials and Methods: We evaluated specimens from 20 patients with urothelial carcinomas of the renal pelvis and ureter who were treated with nephroureterectomy or ureterectomy between June 1997 and January 2007. CAM expression was evaluated by immunohistochemistry in a tissue microarray and correlated with histopathological characteristics and patient outcomes after a mean follow-up of 55 months. Results: We observed a relationship between E-cadherin expression and disease recurrence. Disease recurrence occurred in 87.5% of patients with strong E-cadherin expression. Only 50.0% of patients with moderate expression and 0% of patients with weak or no expression of E-cadherin had disease recurrence (p = 0.014). There was also a difference in disease-free survival. Patients with strong E-cadherin expression had a mean disease-free survival rate of 49.1 months, compared to 83.9 months for patients with moderate expression (p = 0.011). Additionally, an absence of α-catenin expression was associated with tumors that were larger than 3 cm (p = 0.003). Conclusions: We demonstrated for the first time that immune expression of E-cadherin is related to tumor recurrence and disease-free survival rates, and the absence of α-catenin expression is related to tumor size in upper tract urothelial carcinomas

Loss of TIMP-1 immune expression and tumor recurrence in localized prostate cancer

Introduction and objective: Overexpression of MMPs has been related to biochemical recurrence after radical prostatectomy. TIMP1 and TIMP2 are controllers of MMPs and the aim of this study is to evaluate the expression levels of MMPs and their regulators using immunohistochemistry in tissue microarray of localized prostate cancer (PC). Materials and Methods: Immune-expression of MMP-9, MMP-2, TIMP1, TIMP-2, MMP-14 and IL8, were analyzed by immunohistochemistry in radical prostatectomy specimens of 40 patients with localized PC who underwent surgery between September 1997 and February 2000. Protein expression was considered as categorical variables, negative or positive. The results of the immune-expression were correlated to Gleason score (GS), pathological stage (TNM), pre-operatory PSA serum levels and biochemical recurrence in a mean follow up period of 92.5 months. Results: The loss of TIMP1 immune-expression was related to biochemical recurrence. When TIMP1 was negative, 56.3% patients recurred versus 22.2% of those whose TIMP1 was positive (p=0.042). MMP-9, MMP-2, IL8 and MMP-14 were positive in the majority of PC. TIMP-2 was negative in all cases. Conclusion: Negative immune-expression of TIMP1 is correlated with biochemical recurrence in patients with PC possibly by failing to control MMP-9, an important MMP related to cancer progression

Expression of micro-RNAs and genes related to angiogenesis in ccRCC and associations with tumor characteristics

Abstract Background Clear cell renal cell carcinoma (ccRCC) is the third most common urological cancer in adults. Our aim is to evaluate genes and miRNAs expression profiles involved with angiogenesis and tumor characteristics in ccRCC. Methods The expression levels of miRNAs miR-99a, 99b, 100; 199a; 106a; 106b; 29a; 29b; 29c; 126; 200a, 200b and their respective target genes: mTOR, HIF1-α, VHL, PDGF, VEGF, VEGFR1 and VEGFR2 were analyzed using qRT-PCR in tumor tissue samples from 56 patients with ccRCC. Five samples of benign renal tissue were utilized as control. The expression levels of miRNAs and genes were related to tumor size, Fuhrman nuclear grade and microvascular invasion. Results miR99a was overexpressed in most samples and its target gene mTOR was underexpressed, this also occurs for miRNAs 106a, 106b, and their target gene VHL. An increase in miR-200b was correlated with high-risk tumors (p = 0.01) while miR-126 overexpression was associated with Fuhrman’s low grade (p = 0.03). Conclusions Our results show that in ccRCC there are changes in miRNAs expression affecting gene expression that could be important in determining the aggressiveness of this lethal neoplasia

The archaea (2017)

The Archaea’ features a series of constructed photographic tableaux of tangled, botanical phantasmagoria, which refer to the landscape with a suggestion of figuration. Inspired by the ‘Jungle paintings’ of Max Ernst and alluding to Ballardian themes of Nature’s retribution, the resulting images succeed in being both menacing and simultaneously humorous. The high-contrast, backlit, large scale photographs are created in the studio and subsequently manipulated with a digital technique; used here to denote an underlying molecular structure redolent of microscopic photography. This serves to enforce a link between animal and vegetable but also lends the work a painterly quality, paradoxically at odds with the photographic medium. The resulting imagery emits a dreamlike quality that induces the pareidolic illusion latent in the human Psyche, this anthropomorphism further reinforcing the Archean molecular link between everything that exists. All plants, animals and humans, are biologically connected and this genetic inheritance can be traced back to the human brain and spinal column. The split between animals and plants on the Phylogenetic tree occurred around 1.6 million years ago, however with some plant species we still share as much as 75% genetic similarity.N/