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

Arbuscular Mycorrhizal Fungi and Plant Growth Promoting Rhizobacteria Avoid Processing Tomato Leaf Damage during Chilling Stress

Chilling stress limits processing tomato growth and yield, leading to high losses. An approach to increase the sustainability of crop production could involve the use of beneficial microorganisms. The objectives of this research were to investigate: (i) the ecacy of Funneliformis mosseae and Paraburkholderia graminis C4D1M in avoiding processing tomato damage during severe chilling stress; (ii) the synergic eect of the two microorganisms inoculated as a consortium; (iii) if the putative microorganism eects depended on the processing tomato genotype. To achieve these objectives, two experiments were carried out. In the first experiment, a modern genotype was assessed, while three genotypes were evaluated in the second experiment. At sowing, F. mosseae was mixed with peat. Nine days after sowing, P. graminis was inoculated close to the plant\u2019s root collar. After 40 days of seed sowing, chilling treatment was performed at 1 C for 24 h. F. mosseae mainly reduced the cell membrane injuries in term of electrolytic leakage and eciency of photosystem II, after the chilling stress in both experiments. Conversely, in the second experiment, the consortium improved the seedling regrowth, increasing the eciency of photosystem II. In addition, modern genotypes inoculated with microorganisms showed a better seedling regrowth.Chilling stress limits processing tomato growth and yield, leading to high losses. An approach to increase the sustainability of crop production could involve the use of beneficial microorganisms. The objectives of this research were to investigate: (i) the efficacy of Funneliformis mosseae and Paraburkholderia graminis C4D1M in avoiding processing tomato damage during severe chilling stress; (ii) the synergic effect of the two microorganisms inoculated as a consortium; (iii) if the putative microorganism effects depended on the processing tomato genotype. To achieve these objectives, two experiments were carried out. In the first experiment, a modern genotype was assessed, while three genotypes were evaluated in the second experiment. At sowing, F. mosseae was mixed with peat. Nine days after sowing, P. graminis was inoculated close to the plant's root collar. After 40 days of seed sowing, chilling treatment was performed at 1 \ub0C for 24 h. F. mosseae mainly reduced the cell membrane injuries in term of electrolytic leakage and efficiency of photosystem II, after the chilling stress in both experiments. Conversely, in the second experiment, the consortium improved the seedling regrowth, increasing the efficiency of photosystem II. In addition, modern genotypes inoculated with microorganisms showed a better seedling regrowth

Double gamers—can modified natural regulators of higher plants act as antagonists against phytopathogens? The case of jasmonic acid derivatives

As key players in biotic stress response of plants, jasmonic acid (JA) and its derivatives cover a specific and prominent role in pathogens-mediated signaling and hence are promising candidates for a sustainable management of phytopathogenic fungi. Recently, JA directed antimicrobial effects on plant pathogens has been suggested, supporting the theory of oxylipins as double gamers in plant-pathogen interaction. Based on these premises, six derivatives (dihydrojasmone and cis-jasmone, two thiosemicarbazonic derivatives and their corresponding complexes with copper) have been evaluated against 13 fungal species affecting various economically important herbaceous and woody crops, such as cereals, grapes and horticultural crops: Phaeoacremonium minimum, Neofusicoccum parvum, Phaeomoniella chlamydospora, Fomitiporia mediterranea, Fusarium poae, F. culmorum, F. graminearum, F. oxysporum f. sp. lactucae, F. sporotrichioides, Aspergillus flavus, Rhizoctonia solani, Sclerotinia spp. and Verticillium dahliae. The biological activity of these compounds was assessed in terms of growth inhibition and, for the two mycotoxigenic species A. flavus and F. sporotrichioides, also in terms of toxin containment. As expected, the inhibitory effect of molecules greatly varied amongst both genera and species; cis-jasmone thiosemicarbazone in particular has shown the wider range of effectiveness. However, our results show that thiosemicarbazones derivatives are more effective than the parent ketones in limiting fungal growth and mycotoxins production, supporting possible applications for the control of pathogenic fungi

Rational design and validation of a Tip60 histone acetyltransferase inhibitor

Histone acetylation is required for many aspects of gene regulation, genome maintenance and metabolism and dysfunctional acetylation is implicated in numerous diseases, including cancer. Acetylation is regulated by histone acetyltransferases (HATs) and histone deacetylases and currently, few general HAT inhibitors have been described. We identified the HAT Tip60 as an excellent candidate for targeted drug development, as Tip60 is a key mediator of the DNA damage response and transcriptional co-activator. Our modeling of Tip60 indicated that the active binding pocket possesses opposite charges at each end, with the positive charges attributed to two specific side chains. We used structure based drug design to develop a novel Tip60 inhibitor, TH1834, to fit this specific pocket. We demonstrate that TH1834 significantly inhibits Tip60 activity in vitro and treating cells with TH1834 results in apoptosis and increased unrepaired DNA damage (following ionizing radiation treatment) in breast cancer but not control cell lines. Furthermore, TH1834 did not affect the activity of related HAT MOF, as indicated by H4K16Ac, demonstrating specificity. The modeling and validation of the small molecule inhibitor TH1834 represents a first step towards developing additional specific, targeted inhibitors of Tip60 that may lead to further improvements in the treatment of breast cancer

Intratumoral CRH modulates immuno-escape of ovarian cancer cells through FasL regulation

Although corticotropin-releasing hormone (CRH) and Fas ligand (FasL) have been documented in ovarian carcinoma, a clear association with tumour progression and immuno-escape has not been established. FasL plays an important role in promoting tumour cells' ability to counterattack immune cells. Here, we examined immunohistochemically the expression of CRH, CRHR1, CRHR2 and FasL in 47 human ovarian cancer cases. The ovarian cancer cell lines OvCa3 and A2780 were further used to test the hypothesis that CRH might contribute to the immune privilege of ovarian tumours, by modulating FasL expression on the cancer cells. We found that CRH, CRHR1, CRHR2 and FasL were expressed in 68.1, 70.2, 63.8 and 63.8% of the cases respectively. Positivity for CRH or FasL expression was associated with higher tumour stage. Finally, CRH increased the expression of FasL in OvCa3 and A2780 cells through CRHR1 thereby potentiated their ability to induce apoptosis of activated peripheral blood lymphocytes. Corticotropin-releasing hormone produced by human ovarian cancer might favour survival and progression of the tumour by promoting its immune privilege. These findings support the hypothesis that CRHR1 antagonists could potentially be used against ovarian cancer