Sex steroids, carcinogenesis, and cancer progression

The relationship between sex steroids and cancer has been studied for more than a century. Using an original intact cell analysis, we investigated sex steroid metabolism in a panel of human cancer cell lines, either hormone responsive or unresponsive, originating from human breast, endometrium, and prostate. We found that highly divergent patterns of steroid metabolism exist and that the catalytic preference (predominantly reductive or oxidative) is strictly associated with the steroid receptor status of cells. We explored intra-tissue concentrations and profiles of estrogens in a set of human breast tumors as compared to normal mammary tissues, also in relation to their estrogen receptor status. In particular, we showed that, with hydroxyestrogens representing the majority of all tissue estrogens, concentrations of individual metabolites, as well as their ratios, significantly differ when comparing normal tissue with cancer tissues or when they are related to the overall survival of cancer patients. © 2004 New York Academy of Sciences

Retinol oxidation to retinoic acid in human thyroid glandular cells

Retinoic acid is regarded as the retinol metabolite that controls proliferation and differentiation of epithelial cells. In the present study, we investigated the potential role of xanthine dehydrogenase (XDH) in retinoic acid biosynthesis in human thyroid glandular cells (HTGC). In particular, we observed that cellular retinoids binding proteins (CRBPs) are also implicated in the biosynthetic pathway leading to retinoic acid formation in primary cultures of HTGC, as we have already reported for human mammary epithelial cells (HMEC). After partial protein purification, the enzyme responsible for retinoic acid biosynthesis was identified and quantified as XDH by immunoassay, by its ability to oxidize xanthine to uric acid and its sensitivity to the inhibitory effect of oxypurinol. The evidence of XDH-driven formation of retinoic acid in HTGC cultures further corroborates the potential role of XDH in retinoic acid biosynthesis in the epithelia

Profiling Cancer Stem Cells in Androgen-Responsive and Refractory Human Prostate Tumor Cell Lines

In this study, we investigated androgen metabolism in two different human prostate cancer cell lines, the androgen-responsive LNCaP cells and the nonresponsive PC3 cells. Following 24-h and 72-h incubation with either testosterone (T) or androstenedione (Ad) used as precursor, divergent patterns and rates of androgen metabolism were observed. Given the recent interest in the multiple uses of embryonic and adult stem cells for basic and applied research, we compared the expression of three presumptive stem cell markers (Oct-4, SUZ-12, and Cripto-1), along with connexin 43 (Cx43), Cx32, and androgen receptor (AR), used as cell differentiation gene markers. In anchorage-independent cell growth conditions, the expression levels of candidate markers of cancer stem cells initially increased (days 2–4) but drastically fell thereafter (day 6) in both cell lines. Results of immunocytochemical assay (ICA) largely confirmed those obtained by RT-PCR. Interestingly, both symmetrical and asymmetrical cell divisions were revealed in PC3 cells using Oct-4 immunostaining. Our data suggest that both androgen-responsive and androgen-nonresponsive prostate tumor cell lines contain a presumptive cancer stem cell population that can be identified using a panel of selected gene markers, including Oct-4, SUZ-12, and Cripto-1

Intercellular communication and human hepatocellular carcinoma

We have previously reported that gap junction-mediated intercellular communication (GJIC) can be restored in junctionally deficient human prostate epithelial cells, also suggesting that GJIC activity is regulated by estrogen. In the present work, we report studies on sex steroid regulation of GJIC and proliferative activity in both nontumoral (Chang liver, CL) and malignant (HepG2, Huh7) human liver cells. Junctional activity and liver cell growth were measured using the scrape-loading/dye-transfer (SL/DT) and the MTS assay, respectively. Using the SL/DT, only Huh7 cells exhibited a moderate degree of Junctional activity in basic conditions, while neither CL nor HepG2 cells showed functional GJIC. Under exactly the same experimental approach used for prostate studies, we observed that, once again, both estrogen (either estradiol or estrone) and FK induce a significant increase of GJIC in Huh7 cells, while exposure of HepG2 cells to FK produces only a limited rise of Junctional activity in this cell line. However, estrogen induced a significant increase and reduction of the proliferative activity of CL and Huh? cells, respectively, while growth of HepG2 cells was not affected. While the above evidence suggests that estrogens are primarily implicated in growth regulation and communication of both prostate and liver epithelial cells, it also implies that compounds able to restore GJIC in junctionally deficient cells or prevent its disruption in junctionally proficient cells may be used for development of new strategies in the prevention and/or treatment of several human malignancies, including hepatocellular carcinoma (HCC). © 2004 New York Academy of Sciences

Pasta Supplemented with Opuntia ficus-indica Extract Improves Metabolic Parameters and Reduces Atherogenic Small Dense Low-Density Lipoproteins in Patients with Risk Factors for the Metabolic Syndrome: A Four-Week Intervention Study

Food supplementation with Opuntia ficus-indica (OFI) has been associated with a significant reduction in total cholesterol, body fat, hyperglycemia and blood pressure. Since OFI may also have antioxidant and anti-atherogenic properties, we hypothesized that its supplementation might reduce atherogenic lipoproteins, including small, dense low-density lipoproteins (sdLDL). Forty-nine patients (13 men and 36 women, mean age: 56 ± 5 years) with one or two criteria for the metabolic syndrome weekly consumed 500 g of pasta supplemented with 3% OFI extract (30% of insoluble polysaccharides with high antioxidant power) for 1 month. The full LDL subclass profile was assessed by gel electrophoresis (Lipoprint, Quantimetrix, Redondo Beach, CA, USA). After 1 month of pasta supplementation, waist circumference (p = 0.0297), plasma glucose (p < 0.0001), triglycerides (p = 0.0137), plasma creatinine (p = 0.0244), urea and aspartate transaminase (p < 0.0001 for each) significantly decreased. A percentage increase in larger, less atherogenic LDL-1 (p = 0.0002), with a concomitant reduction in smaller, denser LDL-2 (p < 0.0001) and LDL-3 (p = 0.0004), were found. LDL-4 and-5 decreased, although not significantly. This is the first intervention study suggesting that pasta enriched with an OFI extract may have beneficial effects on some metabolic parameters and the LDL particle sizes, reducing atherogenic sdLDL. Future studies will help to establish if these findings impact cardiovascular outcomes

European survey of newborn bloodspot screening for CF: opportunity to address challenges and improve performance

European CF Society Neonatal Screening Working Group (ECFS NSWG): Sabine Renner , Max Zeyda , Elke de Wachter , Luc Regal , Felix Votava, Andrea Holubova, Marianne Skov , Tessa Morgan, Paul Bregeaut , Loretta O'Grady, Ines Bucci , Stefano Pantano , Simonetta Simonetti, Domenica De Venuto, Donatello Salvatore, Nicola Perrotti, Mimma Caloiero, Giuseppe Castaldo, Antonella Tosco, Francesca Righetti, Giovanna Pisi, Fiorella Battistini, Antonio Angeloni, Giuseppe Cimino, Giovanni Fiocchi, Antonella Angiolillo, Michela Cassanello, Luisella Alberti, Laura E Claut, Raffaele Badolato, Enza Pavanello, Benedetta Fabrizzi, Elisabetta Bignamini, Anna Cardillo, Mariangela Lombardo, Letizia Cocciadiferro, Lisa Termini, Daniela Dolce, Vito Terlizzi, Anna Tamanini, Francesca Pauro, Giancarlo la Marca, Elina Aleksejeva, Dita Gaidule-Logina, Stoika Fustik, Violeta Anastasovska, Marelle Bouva, Alastair Reid, Jennifer Cundick, Emma Lundman, Egil Bakkeheim, Katarzyna Zybert, Mariusz Oltarzewski, Laura Vilarinho, Victoria Sherman, Elena Kondratyeva, Sarah Smith, Gordana Vilotijevic Dautovic, Maria Knapkova, Zuzana Mydlova, Rosa Mª López, Valle Velasco, Felicitas Díaz Flores, Cristóbal Colón Mejeras, Eva Sl Pedersen, Ugur Ozcelik, Bulent Karadag, Halyna Makukh, Moat Stuart.European CF Society Neonatal Screening Working Group (ECFS NSWG): INSA - Laura VilarinhoBackground: The aim of this study was to record the current status of newborn bloodspot screening (NBS) for CF across Europe and assess performance. Methods: Survey of representatives of NBS for CF programmes across Europe. Performance was assessed through a framework developed in a previous exercise. Results: In 2022, we identified 22 national and 34 regional programmes in Europe. Barriers to establishing NBS included cost and political inertia. Performance was assessed from 2019 data reported by 21 national and 21 regional programmes. All programmes employed different protocols, with IRT-DNA the most common strategy. Six national and 11 regional programmes did not use DNA analysis. Conclusions: Integrating DNA analysis into the NBS protocol improves PPV, but at the expense of increased carrier and CFSPID recognition. Some programmes employ strategies to mitigate these outcomes. Programmes should constantly strive to improve performance but large datasets are needed to assess outcomes reliably.Highlights: In 2022, newborn bloodspot screening (NBS) for CF is undertaken in 30 European countries, 26 of them are national programmes; Some programmes are still not achieving ECFS standards. Compared to 2014, there is an improvement in sensitivity but a deterioration in achieving a sufficient PPV; There continues to be a wide variety of approaches, but the majority of national programmes are now using DNA analysis as a 2nd tier; This survey demonstrates areas of good practice, but there is considerable scope for improvement in the quality of NBS for CF across Europe; The framework of the 20 parameters to calculate the 8 key outcomes should be part of any annual report of a CF NBS programme, and thus improve future surveys.The survey was funded by the European CF Societyinfo:eu-repo/semantics/publishedVersio