Is telomerase reactivation associated with the down-regulatoin of TGFβ receptor-II expression in human breast cancer?

Background Telomerase is a ribonucleoprotein that synthesizes telomeres and plays an important role in chromosomal stability and cellular immortalisation. Telomerase activity is detectable in most human cancers but not in normal somatic cells. TGF beta (transforming growth factor beta) is a member of a family of cytokines that are essential for cell survival and seems to be down-regulated in human cancer. Recent in vitro work using human breast cancer cell lines has suggested that TGF beta down-regulates the expression of hTERT (human telomerase reverse transcriptase) : the catalytic subunit of telomerase. We have therefore hypothesised that telomerase reactivation is associated with reduced immunohisto-chemical expression of TGF beta type II receptor (RII) in human breast cancer. Methods TGF beta RII immunohistochemical expression was determined in 24 infiltrating breast carcinomas with known telomerase activity (17 telomerase-positive and 7 telomerase-negative). Immunohistochemical expression of TGF beta RII was determined by a breast pathologist who was blinded to telomerase data. Results TGF beta RII was detected in all lesions. The percentage of stained cells ranged from 1–100%. The difference in TGF beta RII expression between telomerase positive and negative tumours was not statistically significant (p = 1.0). Conclusion The results of this pilot study suggest that there is no significant association between telomerase reactivation and TGF-beta RII down-regulation in human breast cancer

SYK expression in human breast cancer

BACKGROUND: Syk (Splenic Tyrosine Kinase) is an intracellular receptor protein kinase involved in cell proliferation, differentiation and phagocytosis. It has been studied in T and B lymphocytes, NK cells and platelets. The strong expression of Syk in mammary gland prompted research into its potential role in mammary carcinogenesis. There have been very few studies about its role in breast cancer with conflicting results. This study aims to investigate the hypothesis that Syk expression is down-regulated in breast cancer compared with ANCT and the association between its expression and clinicopathological parameters. MATERIALS AND METHODS: mRNA was extracted from 48 breast cancer specimens. Relative Syk to ribosomal RNA expression was determined by RT-PCR and Taqman methodology. Mann-Whitney U test was used to examine the association between Syk expression in cancer and ANCT. Spearman's rank correlation test was used to examine the association between Syk expression in tumours and patients' age, tumour size, tumour grade, estrogen and progesterone receptor status, lymph node metastasis, vascular invasion and clinical outcome. RESULTS: The median for the relative value of Syk expression was 0.17 and 0.18 (range: 0.12 – 0.56 and 0.0 – 1.77) for tumours and ANCT respectively. There was no significant association between Syk expression in cancers and ANCT (p= 0.598) nor between Syk expression in tumours and patients' age, tumour size, tumour grade, estrogen and progesterone receptor status, lymph node metastasis, vascular invasion or prognosis. CONCLUSION: This study shows that Syk mRNA expression does not seem to vary between breast tumours and ANCT. Furthermore, we observed no significant association between Syk expression and clinicopathological parameters

hTERT protein expression is independent of clinicopathological parameters and c-Myc protein expression in human breast cancer

Background Telomerase is a ribonucleoprotein enzyme that synthesises telomeres after cell division and maintains chromosomal stability leading to cellular immortalization. Telomerase has been associated with negative prognostic indicators in some studies. The present study aims to detect any association between telomerase sub-units: hTERT and hTR and the prognostic indicators including tumour's size and grade, nodal status and patient's age. Methods Tumour samples from 46 patients with primary invasive breast cancer and 3 patients with benign tumours were collected. RT-PCR analysis was used for the detection of hTR, hTERT, and PGM1 (as a housekeeping) genes expression. Results The expression of hTR and hTERT was found in 31(67.4%) and 38 (82.6%) samples respectively. We observed a significant association between hTR gene expression and younger age at diagnosis (p = 0.019) when comparing patients ≤ 40 years with those who are older than 40 years. None of the benign tumours expressed hTR gene. However, the expression of hTERT gene was revealed in 2 samples. No significant association between hTR and hTERT expression and tumour's grade, stage and nodal status was seen. Conclusion The expression of hTR and hTERT seems to be independent of tumour's stage. hTR expression probably plays a greater role in mammary tumourogenesis in younger women (≤ 40 years) and this may have therapeutic implications in the context of hTR targeting strategies

Antes de GIRLS, Sexo en Nueva York: Factores que definen, acercan y alejan estos dos paradigmas televisivos

Treball Final de Grau en Comunicació Audiovisual. Codi: CA0932. Curs 2013-2014En este Trabajo de Final de Grado se realiza un estudio antropológico y feminista acerca de dos series que autoproclaman serlo: Sexo en Nueva York (1998-2004) y Girls (2012-presente). El feminismo de ambas series será estudiado en los distintos escenarios a través de los cuales los personajes principales y secundarios conviven como ejemplo paradigmático de representación de la mujer en dos contextos (muy) lejanos. Nuestro fin es descubrir si ambas generaciones tienen más aspectos en común de los que puede parecer a simple vista y para ello, analizaremos puntos tan relevantes en estas ficciones como la sexualidad, el amor, la amistad, el feminismo, la moda como identidad y el empleo de la narrativa. Obtendremos datos de diversas fuentes, basándonos principalmente en Sex and The City (Jermyn, 2009) y Reading Sex and The City (Akass y McCabe, 2004) para Sexo en Nueva York y en fuentes más alternativas para Girls. Con la ayuda de estas lecturas esperamos ser capaces de determinar si tanto las mujeres de SENY como las chicas de Girls entienden el feminismo de la misma manera o, si al contrario, las segundas lo rechazan.We propose to analyse the similarities and differences between the TV series, Girls and Sex and The City. The title of my project implies that of which is my final purpose: defining the resemblance that can be found in both shows, but also find what makes them so different: their antithesis. At first instance it seems obvious that the success of these shows is because of its feminine gaze, but there is more. In order to define what makes these shows authentic blockbusters, I will contrast them, considering aspects such as the characters, feminine sexuality, fashion as a fifth element or the huge importance of friendship. All these characteristics will make us understand why these shows, which represent such different types of women from the third wave of feminism, have been converted to worldwide milestones. Hence I will do my research in various supports, such as Deborah Jermynʼs book Sex and The City (2009) or Kim Akass and Janet Mccabeʼs Reading Sex and The city (2004), among others. Due to these readings, we will be able to understand why their protagonists have become the “voices of their generations”, for the thirty-something to forty-plus women and the almost- twenty/twenty-something young ladies, respectively

Plasma Leptin, hTERT Gene Expression, and Anthropometric Measures in Obese and Non-Obese Women with Breast Cancer

Introduction Expression of human telomerase reverse transcriptase (hTERT) occurs in most cancers but its relation with obesity is unclear. This study explores the association between leptin levels and anthropometric indices with hTERT mRNA levels in breast cancer patients of different obesity grades. Materials and methods In this case-control study, 65 breast cancer patients participated. Expression of tissues hTERT mRNA was carried out by real-time reverse transcription polymerase chain reaction. Leptin concentrations were measured by enzyme-linked immunoassay. Results Twelve patients (18.46%) were hTERT negative and 53(81.54%) were positive. hTERT mRNA levels were associated with BMI but not with waist circumference (WC) (r = 0.219, P = 0.22) and waist to hip ratio (WHR) (r = 0.212, P = 0.237). Leptin level and hTERT mRNA levels (r = 0.484, P = 0.008) were correlated as well as BMI and hTERT expression. Conclusions This study has shown a correlation between leptin levels and hTERT expression. These findings may clarify the role of leptin in breast carcinogenesis, and hence obesity could be responsible for increased incidences in breast cancer as well as its progression via enhanced production of leptin

Chemical composition, antioxidant and antibacterial activities of extracts obtained from the roots bark of Arbutus andrachne L. a Lebanese tree.

Context and purpose of the study: The leaves, fruits, barks and roots of Arbutus andrachne L (A. andrachne), have been adopted to have high therapeutic value resulting from the presence of antioxidant compounds such as flavonoids, phenolic and tannins. In the present work, three extracts obtained from A. andrachne roots bark were evaluated for their antioxidant and antibacterial activities .The total phenolic content, flavonoid, condensed tannins and anthocyanins were determined in order to correlate them with the antioxidant activity of extracts.Main findings: The highest amounts of phenolic and tannins were found in the ethyl-acetate, while the anthocyanins ones were highly observed in the methanol-water extract. The lowest IC50 values for DPPH (0.6 µg/mL), and metal chelating assay (13.45µg/mL) were recorded in the ethyl-acetate extract and the methanolic one respetively. Gram positive bacteria (S. aureus and E. faecalis) were more susceptible to the antimicrobial potential of the methanol extract, while E.coli and P. aeruginosa as Gram negative bacteria turned out to be more resistant to the same extract. The ethyl-acetate extract was more effective on E. faecalis than on S. aureus; while E. coli and P. aeruginosa were the most resistant to this extract.Brief summary and potential implications: An appropriate dose of antioxidants derived from A. andrachne bark of the roots extracts in the human diet can help to avoid the risk of contracting diseases where ROS are involved in the pathogenesis. In fact, phenolic compounds in these extracts are among the natural antioxidants being studied by the scientific community due to their biological properties, e.g., antioxidant and antimicrobial activities

Chemical composition, antioxidant and antibacterial activities of extracts obtained from the roots bark of Arbutus andrachne L. a Lebanese tree.

Context and purpose of the study: The leaves, fruits, barks and roots of Arbutus andrachne L (A. andrachne), have been adopted to have high therapeutic value resulting from the presence of antioxidant compounds such as flavonoids, phenolic and tannins. In the present work, three extracts obtained from A. andrachne roots bark were evaluated for their antioxidant and antibacterial activities .The total phenolic content, flavonoid, condensed tannins and anthocyanins were determined in order to correlate them with the antioxidant activity of extracts.Main findings: The highest amounts of phenolic and tannins were found in the ethyl-acetate, while the anthocyanins ones were highly observed in the methanol-water extract. The lowest IC50 values for DPPH (0.6 µg/mL), and metal chelating assay (13.45µg/mL) were recorded in the ethyl-acetate extract and the methanolic one respetively. Gram positive bacteria (S. aureus and E. faecalis) were more susceptible to the antimicrobial potential of the methanol extract, while E.coli and P. aeruginosa as Gram negative bacteria turned out to be more resistant to the same extract. The ethyl-acetate extract was more effective on E. faecalis than on S. aureus; while E. coli and P. aeruginosa were the most resistant to this extract.Brief summary and potential implications: An appropriate dose of antioxidants derived from A. andrachne bark of the roots extracts in the human diet can help to avoid the risk of contracting diseases where ROS are involved in the pathogenesis. In fact, phenolic compounds in these extracts are among the natural antioxidants being studied by the scientific community due to their biological properties, e.g., antioxidant and antimicrobial activities

Constitutively Nuclear FOXO3a Localization Predicts Poor Survival and Promotes Akt Phosphorylation in Breast Cancer

Background: The PI3K-Akt signal pathway plays a key role in tumorigenesis and the development of drug-resistance. Cytotoxic chemotherapy resistance is linked to limited therapeutic options and poor prognosis. Methodology/Principal Findings: Examination of FOXO3a and phosphorylated-Akt (P-Akt) expression in breast cancer tissue microarrays showed nuclear FOXO3a was associated with lymph node positivity (p = 0.052), poor prognosis (p = 0.014), and P-Akt expression in invasive ductal carcinoma. Using tamoxifen and doxorubicin-sensitive and -resistant breast cancer cell lines as models, we found that doxorubicin- but not tamoxifen-resistance is associated with nuclear accumulation of FOXO3a, consistent with the finding that sustained nuclear FOXO3a is associated with poor prognosis. We also established that doxorubicin treatment induces proliferation arrest and FOXO3a nuclear relocation in sensitive breast cancer cells. Induction of FOXO3a activity in doxorubicin-sensitive MCF-7 cells was sufficient to promote Akt phosphorylation and arrest cell proliferation. Conversely, knockdown of endogenous FOXO3a expression reduced PI3K/Akt activity. Using MDA-MB-231 cells, in which FOXO3a activity can be induced by 4-hydroxytamoxifen, we showed that FOXO3a induction up-regulates PI3K-Akt activity and enhanced doxorubicin resistance. However FOXO3a induction has little effect on cell proliferation, indicating that FOXO3a or its downstream activity is deregulated in the cytotoxic drug resistant breast cancer cells. Thus, our results suggest that sustained FOXO3a activation can enhance hyperactivation of the PI3K/Akt pathway. Conclusions/Significance: Together these data suggest that lymph node metastasis and poor survival in invasive ductal breast carcinoma are linked to an uncoupling of the Akt-FOXO3a signaling axis. In these breast cancers activated Akt fails to inactivate and re-localize FOXO3a to the cytoplasm, and nuclear-targeted FOXO3a does not induce cell death or cell cycle arrest. As such, sustained nuclear FOXO3a expression in breast cancer may culminate in cancer progression and the development of an aggressive phenotype similar to that observed in cytotoxic chemotherapy resistant breast cancer cell models. © 2010 Chen et al.published_or_final_versio