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INTRODUCTION: Several studies have already shown that changes in the AR gene may be associated with a more aggressive disease phenotype and even castration-resistant prostate cancer. Thus, we investigated cytogenetic and molecular alterations linked to AR. MATERIALS AND METHODS: To evaluate AR methylation, we performed a cytogenetic-molecular analysis using fluorescence in situ hybridization that uses specific probes for the AR gene (Xq11.12) and the X chromosome centromere. For AR activity, we performed a qualitative analysis of human androgen receptor activity. To analyze the expression of AR in PC3 and LNCaP cell lines, we used qPCR assays. RESULTS: In the qPCR assay, we found downregulation of AR in the PC3 cell line compared with the LNCaP. We found the presence of X chromosome polysomy in PC-3 and LNCaP cell lines by FISH assay. In the HUMARA-Q assay, we found two X chromosomes/cell and the activity of both AR in the PC-3 cell line. In LNCaP cells, we found two X chromosomes/cell and methylation of only one AR. CONCLUSION: Castration-resistant prostate cancer phenotype represents a significant challenge in the setting of urological management. The X chromosomes and AR-linked alterations may contribute to a better understanding of the disease. However, further studies should be performed in an attempt to elucidate as much as possible the role of AR in the castration-resistant prostate cancer phenotype.

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Intratumoral heterogeneity (ITH) represents an obstacle for cancer diagnosis and treatment, but little is known about its functional role in cancer progression. The A Desintegrin And Metalloproteinase 23 (ADAM23) gene is epigenetically silenced in different types of tumors, and silencing is often associated with advanced disease and metastasis. Here, we show that invasive breast tumors exhibit significant ADAM23-ITH and that this heterogeneity is critical for tumor growth and metastasis. We demonstrate that while loss of ADAM23 expression enhances invasion, it causes a severe proliferative deficiency and is not itself sufficient to trigger metastasis. Rather, we observed that, in ADAM23-heterotypic environments, ADAM23-negative cells promote tumor growth and metastasis by enhancing the proliferation and invasion of adjacent A23-positive cells through the production of LGI4 (Leucine-rich Glioma Inactivated 4) and nitric oxide (NO). Ablation of LGI4 and NO in A23-negative cells significantly attenuates A23-positive cell proliferation and invasion. Our work denotes a driving role of ADAM23-ITH during disease progression, shifting the malignant phenotype from the cellular to the tissue level. Our findings also provide insights for therapeutic intervention, enforcing the need to ascertain ITH to improve cancer diagnosis and therapy.

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PURPOSE: To investigate the effects of hypercholesterolemic diet on the collagen composition of urinary bladder wall. MATERIALS AND METHODS: Forty-five female 4-week-old Wistar rats were divided into three groups: 1) control group fed a normal diet (ND); 2) model of bladder outlet obstruction (BOO) group fed a ND; and 3) group fed a HCD (1.25% cholesterol). Total serum cholesterol, LDL cholesterol and body weight were assessed at baseline. Four weeks later, group 2 underwent a surgical procedure resulting in a partial BOO, while groups 1 and 3 underwent a sham similar surgical procedure. Six weeks later, all animals had their bladders removed; serum cholesterol and LDL cholesterol levels and body weights were measured. Morphological and morphometric analysis was performed by Picrosirius staining and collagen types I and III were identified by immunofluorescence. Statistical analysis was completed and significance was considered when p<0.05. RESULTS: Rats fed an HCD exhibited a significant increase in LDL cholesterol levels (p<0.001) and body weight (p=0.017), when compared to the groups fed a ND during the ten-week study period. Moreover, the HCD induced morphological alterations of the bladder wall collagen, regarding thin collagen fibers and the amounts of type III collagen when compared to the control group (p=0.002 and p=0.016, respectively), resembling the process promoted in the BOO model. CONCLUSIONS: A hyper-cholesterolemic diet in Wistar rats promoted morphological changes of the bladder types of collagen, as well as increases in body weight and LDL cholesterol.

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Temporary lakes are common in the semi-arid region of the State of Bahia and form water mirrors in the rainy season. In this period, various vegetal species appear having different life forms adapted to the seasonality conditions of the rainfall regime. This work surveyed the adaptive anatomical structures of some emergent and amphibious monocot species occurring in these lakes. We studied the anatomy of roots, rhizomes, leaves and scapes of Cyperus odoratus, Oxycaryum cubense, Pycreus macrostachyos (Cyperaceae) - amphibious species; and of Echinodorus grandiflorus (Alismataceae), Eichhornia paniculata (Pontederiaceae) and Habenaria repens (Orchidaceae) - emergent species. The anatomical features of the dermal, fundamental and vascular systems confirming the tendency of the adaptive convergence of these plants to temporary lacustrine the environment include: single layered epidermal cells with a thin cuticle layer in the aerial organs; the presence of air canals in all the organs; few or no supporting tissues; and less numerous conducting elements and thinner cell walls in the xylem. The reduction of the supporting tissues, the number of stomata, which can even be absent, and the number of conducting elements and the degree of cell wall lignification in the xylem of the emergent species is more accentuated than that of the amphibious species. The pattern of distribution of aerenchyma in the roots of the studied species was considered important to distinguish between amphibious and emergent life forms.

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Parodiolyra is a member of Olyreae, a tribe of herbaceous bamboo species within the Poaceae. The genus has five species, four of which were previously regarded as belonging to Olyra L. Parodiolyra has a Neotropical distribution and only two species occur on forests in Eastern Brazil: P. micrantha (Kunth) Zuloaga & Davidse and P. ramosissima (Trin.) Soderstr. & Zuloaga, the first widely distributed in the Neotropics while the second is endemic to the state of Bahia. Leaf anatomy of the two species was analysed with the aid of an optical microscope. The objective was to describe the microscopic characters and evaluate if they can be useful for the taxonomy of the genus. The observed anatomical structures did not differ from other genera of herbaceous bamboos, however some characters, both from the mesophyll and the epidermis, were useful to delimit the two species.

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OBJECTIVE: The aim of the study was to develop a new durable animal model (using rabbits) for anatomical-functional evaluation of urethral sphincter deficiency. MATERIALS AND METHODS: A total of 40 New Zealand male rabbits, weighting 2.500 kg to 3.100 kg, were evaluated to develop an incontinent animal model. Thirty-two animals underwent urethrolysis and 8 animals received sham operation. Before and at 2, 4, 8 and 12 weeks after urethrolysis or sham operation, it was performed cystometry and leak point pressure (LPP) evaluation with different bladder distension volumes (10, 20, 30 mL). In each time point, 10 animals (8 from the study group and 2 from the sham group) were sacrificed to harvest the bladder and urethra. The samples were evaluated by H&E and Masson's Trichrome to determine urethral morphology and collagen/smooth muscle density. RESULTS: Twelve weeks after urethrolysis, it was observed a significant decrease in LPP regardless the bladder volume (from 33.7 ± 6.6 to 12.8 ± 2.2 cmH2O). The histological analysis evidenced a decrease of 22% in smooth muscle density with a proportional increase in the collagen, vessels and elastin density (p < 0.01). CONCLUSIONS: Transabdominal urethrolysis develops urethral sphincter insufficiency in rabbits, with significant decrease in LPP associated with decrease of smooth muscle fibers and increase of collagen density. This animal model can be used to test autologous cell therapy for stress urinary incontinence treatment.

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Hymenaea martiana Hayne (Fabaceae-Caesalpinioideae) apresenta grande valor na medicina popular em Caetité. A casca, entrecasca do caule e a resina, são utilizadas no tratamento de diversos males. Neste estudo são apresentadas a caracterização anatômica e histoquímica dos órgãos vegetativos. Amostras foram coletadas e processadas segundo técnicas usuais em anatomia vegetal e histoquímica. Todos os órgãos apresentam, em visão transversal, epiderme unisseriada e cavidades secretoras. Cutícula espessa ocorre em todos os órgãos aéreos. A raiz é tetrarca. Colênquima lacunar foi encontrado no caule. Bainha de fibras esclerenquimáticas envolve os feixes vasculares dos órgãos aéreos. Células pétreas ocorrem no pecíolo. Tricomas tectores ocorrem em ambas as faces da folha. A folha é hipoestomática com estômatos paracíticos e o mesofilo é dorsiventral. Cristais de oxalato de cálcio ocorrem no caule, pecíolo e lâmina foliar. Compostos fenólicos ocorrem na raiz, pecíolo e nervura central da folha. Grãos de amido ocorrem na raiz, caule e pecíolo. Lipídios ocorrem em todos os órgãos. Acredita-se que compostos fenólicos e cavidades secretoras de resina podem justificar a utilidade medicinal da espécie pela população de Caetité.

Hymenaea martiana Hayne (Fabaceae-Caesalpinioideae) shows a great value in folk medicine in Caetité. Its bark, stem-bark and resin are used to treat various ailments. In this study, the anatomical and histochemical characterization of vegetative organs is reported. Samples were collected and processed according to usual techniques of plant anatomy and histochemistry. All organs have, by cross-sectional view, uniseriate epidermis and secretory cavities. Thick cuticle occurs in all aerial organs. The root is tetrarch. Lacunar collenchyma was found in the stem. Sclerenchymatic sheath of fibers surrounds the vascular bundles of the aerial organs. Stone cells occur in the petiole. Trichomes occur on both sides of the leaves. The leaf is hypostomatic with paracytic stomata and the mesophyll is dorsiventral. Calcium oxalate crystals occur in the stem, petiole and leaf blade. Phenolic compounds occur in the root, petiole and midrib of the leaf. Starch grains occur in the root, stem and petiole. Lipids occur in all organs. It is believed that phenolic compounds and resin secretory cavities may justify the use of medicinal species by the population of Caetité.

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The objective of this study was to determine the levels of TERT mRNA and TERT protein expression in stomach precancerous lesions such as intestinal metaplasia (IM) and gastric ulcer (GU) and compare them to gastric cancer (GC). Real-time PCR was performed to detect TERT mRNA expression levels in 35 biopsies of IM, 30 of GU, and 22 of GC and their respective normal mucosas. TERT protein was detected by immunohistochemistry in 68 samples, 34 of IM, 23 of GU, and 11 of GC. Increased TERT mRNA expression levels were observed in a significant number of cases, i.e., 46 percent of IM, 50 percent of GU, and 79 percent of GC. The relative mean level of TERT mRNA after normalization with the β-actin reference gene and comparison with the respective adjacent normal mucosa was slightly increased in the IM and GU groups, 2.008 ± 2.605 and 2.730 ± 4.120, respectively, but high TERT mRNA expression was observed in the GC group (17.271 ± 33.852). However, there were no statistically significant differences between the three groups. TERT protein-positive immunostaining was observed in 38 percent of IM, 39 percent of GU, and 55 percent of GC. No association of TERT mRNA and protein expression with Helicobacter pylori infection or other clinicopathological variables was demonstrable, except for the incomplete type vs the complete type of IM. This study confirms previous data of the high expression of both TERT mRNA and protein in gastric cancer and also demonstrates this type of changed expression in IM and GU, thus suggesting that TERT expression may be deregulated in precursor lesions that participate in the early stages of gastric carcinogenesis.

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The objective of this study was to determine the levels of TERT mRNA and TERT protein expression in stomach precancerous lesions such as intestinal metaplasia (IM) and gastric ulcer (GU) and compare them to gastric cancer (GC). Real-time PCR was performed to detect TERT mRNA expression levels in 35 biopsies of IM, 30 of GU, and 22 of GC and their respective normal mucosas. TERT protein was detected by immunohistochemistry in 68 samples, 34 of IM, 23 of GU, and 11 of GC. Increased TERT mRNA expression levels were observed in a significant number of cases, i.e., 46% of IM, 50% of GU, and 79% of GC. The relative mean level of TERT mRNA after normalization with the ß-actin reference gene and comparison with the respective adjacent normal mucosa was slightly increased in the IM and GU groups, 2.008 ± 2.605 and 2.730 ± 4.120, respectively, but high TERT mRNA expression was observed in the GC group (17.271 ± 33.852). However, there were no statistically significant differences between the three groups. TERT protein-positive immunostaining was observed in 38% of IM, 39% of GU, and 55% of GC. No association of TERT mRNA and protein expression with Helicobacter pylori infection or other clinicopathological variables was demonstrable, except for the incomplete type vs the complete type of IM. This study confirms previous data of the high expression of both TERT mRNA and protein in gastric cancer and also demonstrates this type of changed expression in IM and GU, thus suggesting that TERT expression may be deregulated in precursor lesions that participate in the early stages of gastric carcinogenesis.

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Ginkgo biloba (Egb 761) extract, the most prescribed phytomedicine in Europe for the treatment of cerebral insufficiency and vascular diseases, was tested for its possible protective effects against mitomycin C (MMC)- and cyclophosphamide (CP)-induced mutagenicity using the micronucleus test in mouse bone marrow. The extract was co-administered to mice at doses of 50, 100 and 200 mg/kg (po) with 4 mg/kg (ip) MMC or 24 mg/kg (ip) CP. All doses of Egb 761 were significantly (P < 0.05) effective in reducing the frequency of micronucleated polychromatic erythrocytes, when compared with MMC or CP alone. Based on these results, we suggest that Egb 761 possesses both direct and indirect antimutagenic potential.

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