A glycolytic phenotype is associated with prostate cancer progression and aggressiveness: a role for monocarboxylate transporters as metabolic targets for therapy.

Metabolic adaptation is considered an emerging hallmark of cancer, whereby cancer cells exhibit high rates of glucose consumption with consequent lactate production. To ensure rapid efflux of lactate, most cancer cells express high levels of monocarboxylate transporters (MCTs), which therefore may constitute suitable therapeutic targets. The impact of MCT inhibition, along with the clinical impact of altered cellular metabolism during prostate cancer (PCa) initiation and progression, has not been described. Using a large cohort of human prostate tissues of different grades, in silico data, in vitro and ex vivo studies, we demonstrate the metabolic heterogeneity of PCa and its clinical relevance. We show an increased glycolytic phenotype in advanced stages of PCa and its correlation with poor prognosis. Finally, we present evidence supporting MCTs as suitable targets in PCa, affecting not only cancer cell proliferation and survival but also the expression of a number of hypoxia-inducible factor target genes associated with poor prognosis. Herein, we suggest that patients with highly glycolytic tumours have poorer outcome, supporting the notion of targeting glycolytic tumour cells in prostate cancer through the use of MCT inhibitors.Pertega-Gomes N. and Sousa S. received fellowships from the Portuguese Foundation for Science and Technology (FCT), refs. SFRH/BD/61027/2009, and PTDC/SAU-MET/113415/2009, respectively. Felisbino S. received a fellowship from the Sao Paulo Research Foundation (FAPESP) ref. 2013/08830-2 and 2013/06802-1. We thank the core facilities at the Cancer Research UK Cambridge Institute led by James Hadfield (Genomics), Matt Eldridge (Bioinformatics) and Allen Hazelhurst (BRU). We also thank the support and critical advice on the project given by Christian Frezza and Marco Sciacovelli from The MRC Cancer Cell Unit and Professor Rui Henrique from Portuguese Institute of Oncology for providing samples from patients with metastatic prostate cancer.This is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1002/path.454

The expression of monocarboxylate transporters in thyroid carcinoma can be associated with the morphological features of BRAF (V600E) mutation

BRAF (V600E) mutation, usually performed by DNA techniques, is one of the most common diagnostic markers in papillary thyroid carcinoma. Few papers have demonstrated that plump cells (eosinophilic cytoplasms and papillary thyroid carcinoma nuclei) and peculiar sickle-shaped nuclei represent morphological features of BRAF (V600E) on papillary thyroid carcinomas. These features seem to be linked to glycolytic phenotype whereby monocarboxylate transporters 1-4 are hypothesized to have a dominant role as lactate transporters. We investigated the association between these morphological features and monocarboxylate transporters 1 and 4 in 48 cyto-histological samples diagnosed as "positive for malignancy-favoring papillary thyroid carcinoma". These cases were processed with liquid-based cytology and underwent BRAF (V600E) mutational analysis (pyrosequencing) on liquid-based cytology and monocarboxylate transporters immunostaining on histology. The expression of monocarboxylate transporter 1, monocarboxylate transporter 4, glucose trasporter-1 and carbonic anhidrase were scored semi-quantitatively with expression from 0 to 3+ (strong positivity). The 33 mutated and 15 wild type cases showed 100 % cyto-histological concordance. The cytological evaluation revealed plump cells and sickle nuclear shape in 100 % mutated cases. Monocarboxylate transporter 1 yielded 76 % positivity in the mutated cases especially in both the plump cells and sickle-shaped nuclei, whereas the wild types showed 13.3 % positive monocarboxylate transporter 1 (p = 0.00013). Monocarboxylate transporter 4 resulted in 100 % positivity in mutated and 40 % in wild types (p 0.05). This is the first report analyzing the association between monocarboxylate transporter expression and the morphological features of BRAF (V600E) mutated papillary thyroid carcinomas suggesting the possible involvement of lactate in the morphological features.info:eu-repo/semantics/publishedVersio

Studies of the enzymology of fatty acid oxidation and of methyl ketone production in Aspergillus niger

SIGLEAvailable from British Library Document Supply Centre-DSC:DXN022604 / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Jane & Louise Wilson: o rescaldo do tempo histórico e a mediação artística

status: publishe

Is that your final answer?: a descriptive study on attribution of success and failure in television game shows.

This descriptive study aims to determine the attributions of success and failure of the organizers/hosts, contestants and the audience participating in television game shows through their feelings and behavior. The study focused on game shows, such as Who Wants To Be A Millionaire, The Weakest Link, and Game KNB?. There were 184 respondents who participated in the study, 9 of them were organizers, 75 of them were contestants, while the remaining 100 were audiences. The 9 organizers consisted of 3 organizers from each of the three game shows. The contestants were broken down into 42 winners and 63 losers. On the other hand, 50 of the audiences consisted of studio audiences while the remaining half consisted of home audiences. The researchers used a non-probability type of sampling design, wherein purposive sampling was used for the organizers/hosts and contestants while convenient sampling was used for the audience. Structured interview guides and surveys were used as instruments in this study. The data from the interviews and the survey questionnaires were assessed using content analysis. Organizers/hosts attributed the success of the game show to the number of sponsors and callers, ratings and positive feedback from viewers. The contestants attributed their success or failure to God, destiny or luck, which leads to the Filipinos\u27 fatalistic attitude and strong faith in God. Lastly, the audience attributed the success and failure of the contestants through internal causes like cleverness and alertness

Expression of Monocarboxylate Transporters 1, 2, and 4 in Human Tumours and Their Association with CD147 and CD44

Monocarboxylate transporters (MCTs) are important cellular pH regulators in cancer cells; however, the value of MCT expression in cancer is still poorly understood. In the present study, we analysed MCT1, MCT2, and MCT4 protein expression in breast, colon, lung, and ovary neoplasms, as well as CD147 and CD44. MCT expression frequency was high and heterogeneous among the different tumours. Comparing with normal tissues, there was an increase in MCT1 and MCT4 expressions in breast carcinoma and a decrease in MCT4 plasma membrane expression in lung cancer. There were associations between CD147 and MCT1 expressions in ovarian cancer as well as between CD147 and MCT4 in both breast and lung cancers. CD44 was only associated with MCT1 plasma membrane expression in lung cancer. An important number of MCT1 positive cases are negative for both chaperones, suggesting that MCT plasma membrane expression in tumours may depend on a yet nonidentified regulatory protein

Comparison of routine prenatal iron prophylaxis and screening and treatment for anaemia: pregnancy results and preliminary birth results from a pragmatic randomised controlled trial (PROFEG) in Maputo, Mozambique

OBJECTIVE: To present the pregnancy results and interim birth results of a pragmatic randomised controlled trial comparing routine iron prophylaxis with screening and treatment for anaemia during pregnancy in a setting of endemic malaria and HIV. DESIGN: A pragmatic randomised controlled trial. SETTING: Two health centres (1° de Maio and Machava) in Maputo, Mozambique, a setting of endemic malaria and high prevalence of HIV. PARTICIPANTS: Pregnant women (≥18-year-olds; non-high-risk pregnancy, n=4326) attending prenatal care consultation at the two health centres were recruited to the trial. INTERVENTIONS: The women were randomly allocated to either Routine iron (n=2184; 60 mg ferrous sulfate plus 400 μg of folic acid daily throughout pregnancy) or Selective iron (n=2142; screening and treatment for anaemia and daily intake of 1 mg of folic acid). OUTCOME MEASURES: The primary outcomes were preterm delivery (delivery <37 weeks of gestation) and low birth weight (<2500 g). The secondary outcomes were symptoms suggestive of malaria and self-reported malaria during pregnancy; birth length; caesarean section; maternal and child health status after delivery. RESULTS: The number of follow-up visits was similar in the two groups. Between the first and fifth visits, the two groups were similar regarding the occurrence of fever, headache, cold/chills, nausea/vomiting and body aches. There was a suggestion of increased incidence of self-reported malaria during pregnancy (OR 1.37, 95% CI 0.98 to1.92) in the Routine iron group. Birth data were available for 1109 (51%) in the Routine iron group and for 1149 (54%) in the Selective iron group. The birth outcomes were relatively similar in the two groups. However, there was a suggestion (statistically non-significant) of poorer outcomes in the Routine iron group with regard to long hospital stay after birth (relative risk (RR) 1.43, 95% CI 0.97 to 1.26; risk difference (RD) 0.02, 95% CI −0.00 to 0.03) and unavailability of delivery data (RR 1.06, 95% CI 1.00 to 1.13; RD 0.03, 95% CI −0.01 to 0.07). CONCLUSIONS: These interim results suggest that routine iron prophylaxis during pregnancy did not confer advantage over screening and treatment for anaemia regarding maternal and child health. Complete data on birth outcomes are being collected for firmer conclusions. TRIAL REGISTRATION: The trial is registered at ClinicalTrials.gov, number NCT00488579 (June 2007). The first women were randomised to the trial proper April 2007–March 2008. The pilot was November 2006–March 2008. The 3-month lag was due to technical difficulties in completing trial registration

Is selective prenatal iron prophylaxis better than routine prophylaxis: final results of a trial (PROFEG) in Maputo, Mozambique

OBJECTIVE: To compare routine versus selective (ie, screening and treatment for anaemia) prenatal iron prophylaxis in a malaria-endemic and HIV-prevalent setting, an extended analysis including previously missing data. DESIGN: A pragmatic randomised controlled clinical trial. SETTING: 2 health centres in Maputo, Mozambique. PARTICIPANTS: Pregnant women (≥18 years old; non-high-risk pregnancy) were randomly allocated to routine iron (n=2184) and selective iron (n=2142) groups. INTERVENTIONS: In the routine group, women received 60 mg ferrous sulfate plus 400 μg folic acid daily. In the selective group, women received 1 mg of folic acid daily and haemoglobin (Hb) screening at each visit; with low Hb (cut-off 9 g/dL) treatment (120 mg+800 μg of folic acid daily) for a month. OUTCOME MEASURES: Primary outcomes: preterm birth, low birth weight; secondary outcomes: self-reported malaria, labour complications, caesarean section, perinatal death, woman's death. Nurses collected pregnancy data. Birth data were abstracted from hospital records for 52% of women and traced using various methods and linked with probabilistic matching for 24%. Women's deaths were collected from death registers. RESULTS: Birth data were available for 3301 (76%) of the women. Outcomes were similar in the two groups: preterm births (27.1% in the selective vs 25.3% in the routine group), low birthweight infants (11.0% vs 11.7%), perinatal deaths (2.4% vs 2.4%) and caesarean sections (4.0% vs 4.5%). Women's deaths during pregnancy or <42 days postpartum were more common in the selective group (0.8% among the two best matched women) than in the routine group (0.4%). Extra deaths could not be explained by the cause of death, Hb level or HIV status at recruitment. CONCLUSIONS: Birth outcomes were similar in the two iron groups. There might have been more women's deaths in the selective iron group, but it is unclear whether this was due to the intervention, other factors or chance finding. TRIAL REGISTRATION NUMBER: NCT00488579