Lymphoepithelial carcinoma of the larynx: An unusual response to EXTREME regimen therapy. A new option for treatment?

Lymphoepithelial Carcinoma (LEC), an aggressive variant of Squamous Cell Carcinoma (SCC), is an undifferentiated carcinoma with an intermixed reactive lymphoplasmacytic infiltrate. Most cases of LEC occur in the nasopharynx, while it rarely involves other sites. LEC of larynx and hypopharynx is an extremely rare and aggressive neoplasm, characterized by a high propensity to loco-regional dissemination and a poor prognosis; it represents the 0,2% of all tumours of the larynx. Since it is such a rare tumor, the current literature provides only recommendations and there are no treatment guidelines available. A 70-year-old man with laryngeal LEC and both distant and nodal metastases was treated with chemotherapy, following EXTREME regimen therapy. It was classified as a cT3 N3b M1 glottic cancer (Stage IVC, AJCC 8th Ed.), stage IVC. As the response on metastases was unexpectedly encouraging, surgical treatment on T could be performed. Patient underwent to total laryngectomy and bilateral neck dissection. To date, eight months after surgery, the patient is disease free. The unusual clinical course is reported.

Airborne microbial flora in buffalo farms in a Mediterranean climate

The last few decades have seen an increase in intensive buffalo farms worldwide. Such industrialized activity entails human and animal potential health-related hazards as well as for the environment. Given the breadth of the issue, in this study we focused on gathering microbiological air sampling in the Southern Italian buffalo farms in order to obtain further information on airborne microbial flora. In details, we evaluated the bio-aerosol concentration of cultivable bacteria and fungi in ten different buffalo farms. There are evidences showing that exposure to organic dust may exacerbate asthma, just as it may cause mucous membrane irritation and chronic bronchitis. Likewise, studies show that inhaling noninfectious microorganisms and their components may cause inflammation of the respiratory tract. As a result, this is a significant health hazard to these farms’ workers as well as to rural residents living closely to them.

Antibacterial and antiviral potential of neuropeptides

The emergence of multidrug resistant bacteria is a global health threat and the discovery of new antimicrobial agents is an absolute priority. In this context endogenous peptides are emerging as novel potential candidates. In this work, we assessed the antimicrobial effects of orexins and ghrelin neuropeptides against gram-negative (Escherichia coli, Salmonella typhimurium, Klebsiella pneumoniae) and gram-positive (Staphylococcus aureus) bacteria. Orexin-B and ghrelin showed a potent bactericidal effect at concentration equal to or greater than 25 μg/ml. No antimicrobial activity has been observed for orexin-A. Furthermore, we investigated the antiviral proprieties of the three peptides against herpes simplex virus 1 (HSV-1). We found that orexin-B, but not orexin-A is effective for HSV-1 infectivity inhibition.

Relationship between type 2 diabetes and pancreatic cancer

Diabetes mellitus and cancer are conditions that constitute a serious problem for the health of the world’s population, and their co-existence in the same person is becoming increasingly common. Glucose metabolism and the presence of insulin in inflammatory situations appear to be the main factors driving this association, where hyperinsulinemia has been shown to contribute to an increase in risk of association between type 2 diabetes and cancer. Therefore, administering lower levels of exogenously administered insulin to patients with type 1 diabetes would decrease their risk of developing cancer when compared to patients with type 2 diabetes. The results from animal experiments seem promising in terms of pharmacological treatment.

Application of omic technologies in cancer research

Understanding the biology of health and diseases such as cancer, generating insight into the triggers and potentiators of disease and the development of therapeutic approaches to counter and treat disease requires detailed interrogation of inherited genes, and the dynamic positioning of the transcriptome and proteome. In the last 10 years, significant technological developments and increases in sample throughput capabilities have led to a dramatic increase in the size and complexity of the datasets that can be generated. A key challenge now is to develop robust approaches for analysing and interpreting these, and converting data into biologically- and clinically-relevant information. Herein, we provide an overview of approaches for acquiring, integrating and interpreting complex datasets generated using multiple omic platforms, with a focus on the field of cancer research, and highlight key successful data handling and integration applications.

Polycaprolactone nanofiber mesh with adhered liposomes as a simple delivery system for bioactive growth factors

Polycaprolactone (PCL) nanofibers were prepared using electrospinning and functionalized with liposomes containing growth factors by simple surface adhesion. A tight interaction between the liposomes and PCL nanofibers has been clearly demonstrated. Additionally, the interaction of the liposomes with the PCL nanofibers was visualized by FESEM. The potential of the liposome-immobilized scaffold as a delivery system for synthetic growth factors, and as a suitable system for mesenchymal stem cells (MSCs) adhesion and proliferation, was evaluated by confocal microscopy, DNA synthesis rate and dsDNA amount determination. The results showed that the growth factors adhered to the surface of the PCL nanofibers stimulated cell proliferation mainly up to day 7, and that afterwards their effect was significantly lower. By contrast, the release of growth factors from liposomes resulted in gradual proliferation of MSCs throughout the whole experiment. Moreover, the functionalized nanofibers stimulated type II collagen production, which was confirmed by immunohistochemical staining using monoclonal antibody against type II collagen. The study has indicated that growth factor-enriched liposomes adhered to the PCL nanofiber system could be useful as a drug delivery tool in various biomedical applications.

Anaplastic lymphoma tyrosine kinase oncogene in human cancer: gene aberrations, methods of detection and therapeutic potential

Anaplastic lymphoma tyrosine kinase (ALK) gene could be an attractive oncotarget in human cancers, since it is involved in several genetic alterations resulting in an aberrant activity of the receptor. To date, ALK-rearrangement represents a molecular target for the treatment of ALK-rearranged Non Small Cell Lung Cancer patients, who are highly sensitive to crizotinib, a specific inhibitor. ALK-rearranged patients treated with crizotinib show relevant clinical implications, however several different resistance mechanisms have been identified. Here we review various critical issues related to ALK-targeting therapy, including ALK gene aberrations, methods of detection, mechanism of acquired resistance and second-generation ALK inhibitors.

New molecular targets for the treatment of neovascular age-related macular degeneration

Age-related macular degeneration (AMD) is a progressive chronic disease that currently represents the leading cause of irreversible vision loss in the western world. Experimental and clinical evidence has demonstrated that vascular endothelial growth factor A (VEGF-A) plays an important role in promoting the choroidal neovascularization that characterizes the wet form of AMD. Intravitreal injection of anti- VEGF-A agents is the current treatment of choice for neovascular AMD (nAMD). These agents have brought about dramatic changes in the treatment of nAMD, but most patients require frequently repeated injections and regular long-term follow-up, with a significant percentage of them showing resistance to anti-VEGF-A drugs. Thus, the identification of additional therapies that could improve the treatment protocols is needed. There are numerous areas of investigation into new treatments, with increasing efforts being made to study drugs that address various targets along the angiogenic signaling cascade, or other pathways related to the onset of nAMD. The aim of the present review is to summarize and discuss promising new therapies and targets that have the potential to improve outcomes and to lengthen treatment durability, especially in patients with recalcitrant or recurrent forms of nAMD.

The role of mouse models in translational cancer research: present and future directions

A major issue in the research for new anticancer therapeutics is represented by the low number of new compounds approved for clinical use in comparison to the good success rate reported in preclinical studies. This high attrition rate could be attributed to many factors including the unsatisfactory predictive value of experiments performed in animals. To this purpose, general opinions suggest that classical models as murine tumors and xenografts do not mimic the complexity of human cancer diseases and that the use and integration of different relevant mouse models could improve the efficiency of the drug development process. In this review, we overview the present state of research in the field of mouse models for cancer and describe the advantages and limitations of the different models. Finally, strategies for improving the predictive value of animal experiments will be also discussed.

Species specificity of an adrenal androgen-mediated kill-switch triggered by p53 inactivation

Glucose-6-phosphate dehydrogenase (G6PD) is an oncoprotein that is regulated by the p53 tumor suppressor. Mutant p53 loses the ability to inhibit G6PD, and loss of G6PD control clearly plays a role in oncogenesis. The steroid hormone precursor dehydroepiandrosterone (DHEA) is an endogenous uncompetitive inhibitor of G6PD. In humans, and a few other species, the sulfated circulatory form of DHEA (DHEAS) is present at extremely high concentrations – much higher than can be accounted for by DHEA’s function as a precursor to steroid hormones. Uncompetitive inhibition is extremely rare in natural systems because it is irreversible in the presence of high concentrations of substrate and inhibitor. What has gone unappreciated is that such uncompetitive inhibition can quickly lead to cell death when the target is an obligatory housekeeping gene such as G6PD. Cells with inactivated p53 not only lose control over G6PD, but also over hexokinase (HK), the enzyme that converts glucose into glucose-6-phosphate (G6P), the substrate of G6PD. Furthermore, loss of p53 function de-represses NFκB activity, resulting in the upregulation of steroid sulfatase (SS) which converts circulating DHEAS into active DHEA. We propose that inactivation of p53 rapidly elevates G6P and DHEA concentrations in affected cells, driving uncompetitive inhibition of G6PD to lethal irreversibility. In animals with circulating DHEAS, this kill-switch mechanism may prevent most cases of p53 inactivation from becoming tumorigenic. Tumors would thus represent instances in which this mechanism had not been triggered, but which might still be triggered by application of DHEA sufficient to uncompetitively inhibit tumor G6PD. To test this hypothesis, we performed a pilot study in which dogs with cardiac hemangiosarcoma were treated with high dose (HD) DHEA supplemented with isoprene precursors to maintain geranylation of Rac GTPase. Tumor regression and longevity observed in these dogs supported the concept that some tumors retain extraordinary sensitivity to uncompetitive inhibition by DHEA.