The LH/hCG Axis in Endometrial Cancer: A New Target in the Treatment of Recurrent or Metastatic Disease

Endometrial cancer (EC) is a hormone-dependent cancer that currently represents the most frequent malignancy of the female reproductive tract. The involvement of steroid hormones in EC etiology and progression has been reported. More recently, gonadotropins, and, in particular LH/hCG, are emerging as novel regulators of tumor progression. In the present review, we discuss the role of the LH/hCG axis (i.e. LH/hCG and its receptors, LH/hCG-R) in both gonadal and nongonadal tissues, in physiological and neoplastic conditions. In cancer cells, LH/hCG mainly controls cell proliferation and apoptosis. In particular, in EC LH/hCG improves cell invasiveness, through a mechanism which involves the LH/hCG-R, which in turn activate protein kinase A and modulate integrin adhesion receptors. Indeed, the LH/hCG-R mRNA is expressed in primary ECs and this expression correlates with LH/hCG-induced cell invasiveness in vitro. These results lead to hypothesize that recurrent and metastatic ECs, which express LH/hCG-R, could benefit from therapies aimed at decreasing LH levels, through Gn-RH analogues. Hence, the LH/hCG axis could represent a prognostic factor and a new therapeutic target in EC

Lipid Oxidation and Sensory Characteristics of Grass-Fed Beef: Effect of Duration of Grazing Prior to Slaughter

Beef from cattle produced from grass has a higher concentration of fatty acids considered to be beneficial to human health than beef produced from more intensive production systems and this increase in fatty acid concentration is dependant on the duration at pasture prior to slaughter (Noci et al., 2003). Improvements in the fatty acid composition of beef must not impair other quality characteristics of beef. Little information is available on the pattern of change of quality characteristics in grazing animals. The objective of this study was to determine the shelf-life and eating quality of beef from cattle produced from a standard Irish grass silage/concentrates finishing system but allowed to graze grass for different periods prior to slaughter

Enhancement of the Nutritional Value and Eating Quality of Beef

End of Project ReportThis project was supported by the European Commission (Healthy Beef, QLRT-CT-2000-31423).Consumer interest in the nutritional aspects of health has increased interest in developing methods to manipulate the fatty acid composition of ruminant products. Ruminant meats such as beef and lamb are often criticised by nutritionists for having high amounts of saturated fatty acids (S) and low polyunsaturated fatty acids (P).The P:S ratio in beef is approximately 0.1, the ideal being about 0.4. This project is part of a larger EU-supported project entitled Healthy Beef (Enhancing the content of beneficial fatty acids in beef and improving meat quality for the consumer: QLRT-CT-2000-31423). The Teagasc contribution, which was a collaboration between Grange Research Centre and The National Food Centre, focussed on nutritional manipulation of beef cattle. In particular, on exploiting grazing and fishoil as tools to enhance the concentration of “healthy” fatty acids in beef. The conclusions were: • The beneficial effect of a grazed grass-based diet on the fatty acid composition of beef was confirmed • The scale of this beneficial effect is strongly dependent on the duration of grazing • The optimum concentration of beneficial fatty acids was not achieved suggesting that feeding management prior to grazing is important • Grazing influenced beef colour and drip-loss in a durationdependent manner • Animals finished off grass for 40 or 98 days produced meat that was tougher than that from animals finished on silage and concentrates or fed grass for the last 158 days. • Fish oil supplementation enhanced the concentration in beef, of fatty acids that are beneficial to human health • The linear response to increasing level of fish oil consumption indicates scope to further enhance the concentrations of beneficial fatty acids in beef Wilting of grass prior to ensiling did not impact negatively on the overall content of n-3P in muscle, but it increased the concentration of conjugated linoleic acid • Dietary inclusion of fish oil or wilting of grass prior to ensiling did not affect muscle appearance • Fish oil seemed to increase tenderness but only at the high level of inclusion. This merits further study • There was some evidence that wilting of grass prior to ensiling enhanced meat tenderness. This needs to be confirmed.European Unio

The lung microbiota: role in maintaining pulmonary immune homeostasis and its implications in cancer development and therapy

Like other body districts, lungs present a complex bacteria community. An emerging function of lung microbiota is to promote and maintain a state of immune tolerance, to prevent uncontrolled and not desirable inflammatory response caused by inhalation of harmless environmental stimuli. This effect is mediated by a continuous dialog between commensal bacteria and immune cells resident in lungs, which express a repertoire of sensors able to detect microorganisms. The same receptors are also involved in the recognition of pathogens and in mounting a proper immune response. Due to its important role in preserving lung homeostasis, the lung microbiota can be also considered a mirror of lung health status. Indeed, several studies indicate that lung bacterial composition drastically changes during the occurrence of pulmonary pathologies, such as lung cancer, and the available data suggest that the modifications of lung microbiota can be part of the etiology of tumors in lungs and can influence their progression and response to therapy. These results provide the scientific rationale to analyze lung microbiota composition as biomarker for lung cancer and to consider lung microbiota a new potential target for therapeutic intervention to reprogram the antitumor immune microenvironment. In the present review, we discussed about the role of lung microbiota in lung physiology and summarized the most relevant data about the relationship between lung microbiota and cancer

Luteinizing Hormone/Human Chorionic Gonadotropin Receptor Immunohistochemical Score Associated with Poor Prognosis in Endometrial Cancer Patients.

The aim of this study was to develop a scoring system of the immunohistochemical (IHC) expression of luteinizing hormone/human chorionic gonadotropin receptor (LHCG-R) in endometrial cancer (EC) patients. Nonconsecutive hysterectomy specimens containing EC collected from April 2013 to October 2015 were selected. Hematoxylin-eosin stained sections from each case were reviewed and representative sections from each tumor were selected. IHC staining was performed for the detection of LHCG-R. The percentage of stained cells and the staining intensity were assessed in order to develop an immunohistochemical score. Moreover, we examined the correlation of the score with grading and lymphovascular space invasion (LVSI). There was a statistically significant positive correlation between grading and IHC scoring (p=0.01) and a statistically significant positive correlation between LVSI and IHC score (p<0.01). In conclusion, we suggest that the immunohistochemical score presented here could be used as a marker of bad prognosis of EC patients. Nevertheless, further studies are needed in order to validate it. The study was registered in the Careggi Hospital public trials registry with the following number: 2013/0011391

Improved Constraints on the Preferential Heating and Acceleration of Oxygen Ions in the Extended Solar Corona

We present a detailed analysis of oxygen ion velocity distributions in the extended solar corona, based on observations made with the Ultraviolet Coronagraph Spectrometer (UVCS) on the SOHO spacecraft. Polar coronal holes at solar minimum are known to exhibit broad line widths and unusual intensity ratios of the O VI 1032, 1037 emission line doublet. The traditional interpretation of these features has been that oxygen ions have a strong temperature anisotropy, with the temperature perpendicular to the magnetic field being much larger than the temperature parallel to the field. However, recent work by Raouafi and Solanki suggested that it may be possible to model the observations using an isotropic velocity distribution. In this paper we analyze an expanded data set to show that the original interpretation of an anisotropic distribution is the only one that is fully consistent with the observations. It is necessary to search the full range of ion plasma parameters to determine the values with the highest probability of agreement with the UVCS data. The derived ion outflow speeds and perpendicular kinetic temperatures are consistent with earlier results, and there continues to be strong evidence for preferential ion heating and acceleration with respect to hydrogen. At heliocentric heights above 2.1 solar radii, every UVCS data point is more consistent with an anisotropic distribution than with an isotropic distribution. At heights above 3 solar radii, the exact probability of isotropy depends on the electron density chosen to simulate the line-of-sight distribution of O VI emissivity. (abridged abstract)Comment: 19 pages (emulateapj style), 13 figures, ApJ, in press (v. 679; May 20, 2008

Poly(I:C) and CpG-ODN combined aerosolization to treat lung metastases and counter the immunosuppressive microenvironment

The immunostimulatory ability of synthetic oligonucleotides containing CpG motifs (CpG-ODN), agonists of Toll-like receptor 9 (TLR9), can be harnessed to promote antitumor immunity by their application at the tumor site to stimulate local activation of innate immunity; however, particularly in the lung, tumor-associated immunosuppression can subvert such antitumor innate immune responses. To locally maintain continuous activation of innate subpopulations while inhibiting immunosuppressive cells, we evaluated aerosol delivery CpG-ODN combined with Poly(I:C), a TLR3 agonist able to convert tumor-supporting macrophages to tumoricidal effectors, in the treatment of B16 melanoma lung metastases in C57BL/6 mice. Aerosolization of CpG-ODN with Poly(I:C) into the bronchoalveolar space reduced the presence of M2-associated arginase- and IL-10-secreting macrophages in tumor-bearing lungs and increased the antitumor activity of aerosolized CpG-ODN alone against B16 lung metastases without apparent signs of toxicity or injury of the bronchial-bronchiolar structures and alveolar walls. Moreover, CpG-ODN/Poly(I:C) aerosol combined with dacarbazine, a therapeutic agent used in patients with inoperable metastatic melanoma able to exert immunostimulatory effects, led to a significant increase in antitumor activity as compared to treatments with aerosolized CpG-ODN/Poly(I:C) or dacarbazine alone. This effect was related to an enhanced recruitment and cytotoxic activity of tumor-infiltrating NK cells in the lung. Our results point to aerosol delivery as a convenient approach for repeated applications of immunostimulants in patients with lung metastases to maintain a continuous local activation of innate immune cells while suppressing polarization of tumor-infiltrating macrophages to an M2 phenotype

Toll-like receptor 3 as a new marker to detect high risk early stage Non-Small-Cell Lung Cancer patients

Immune and epithelial cells express TLR3, a receptor deputed to respond to microbial signals activating the immune response. The prognostic value of TLR3 in cancer is debated and no data are currently available in NSCLC, for which therapeutic approaches that target the immune system are providing encouraging results. Dissecting the lung immune microenvironment could provide new prognostic markers, especially for early stage NSCLC for which surgery is the only treatment option. In this study we investigated the expression and the prognostic value of TLR3 on both tumor and immune compartments of stage I NSCLCs. In a cohort of 194 NSCLC stage I, TLR3 immunohistochemistry expression on tumor cells predicted a favorable outcome of early stage NSCLC, whereas on the immune cells infiltrating the tumor stroma, TLR3 expression associated with a poor overall survival. Patients with TLR3-positive immune infiltrating cells, but not tumor cells showed a worse prognosis compared with all other patients. The majority of TLR3-expressing immune cells resulted to be macrophages and TLR3 expression associates with PD-1 expression. TLR3 has an opposite prognostic significance when expressed on tumor or immune cells in early stage NCSCL. Analysis of TLR3 in tumor and immune cells can help in identifying high risk stage I patients for which adjuvant treatment would be beneficial