Treatment of refractory and relapsed Hodgkin's lymphoma: Facts and perspectives

The most effective salvage strategy for patients with Hodgkin's lymphoma relapsed or refractory to front-line therapy has yet to be conclusively defined. This problem has evolved in the last years and it is time to reconsider its dimension and to comment on mature data, new facts and perspective

Neuroendocrine Mediators, Food Intake and Obesity: A Narrative Review

Obesity is a chronic multifactorial disease caused by imbalance between caloric intake and energy expenditure. The Neuroendocrine system is one of the main factors regulating energy intake in humans. The Neuroendocrine system is made up of cells able to synthesize and secrete amines, peptides, growth factors and biological mediators, known as neurohormones, which modulate various biological functions by interacting with the nervous and immune system. In the central nervous system, neurosecretory elements are mainly located in the hypothalamus which is the anatomical site of the hunger (lateral nucleus) and satiety (ventromedial nucleus) centers; thus it plays a key role in chemical coding of food intake. Dopamine, Noradrenaline and Serotonin are historically considered key points in the regulation of feeding behavior. However, other neurohormones have been identified; these substances, also synthesized in peripheral tissues (especially adipose tissue and digestive tract), influence food intake. Some of these hormones have orexigenic activity; conversely, other substances have anorexigenic activity. A constant balance between orexigenic and anorexigenic neurohormones is essential to ensure a smooth feeding behavior, whereas a subtle and progressive disruption of neurochemical transmission is sufficient to induce hyperphagia or anorexia. Several factors affect the synthesis and release of neuropeptides: genetic, hormonal, psychological, environmental, receptorial, type of feeding and meal frequency. In the recent past some drugs, as Sibutramine and Rimonabant, modulating the activity of several neuroendocrine mediators (Serotonin, Noradrenaline, Endocannabinoids), have proven to be effective in reducing weight excess, even if they were withdrawn because of serious side effects. Recently, promising results in this way have been obtained with Glucagon like Peptide-1 analogs, showing significant efficacy in counteracting weight excess without side effects. Further knowledge developments on these complex neuroendocrine circuits and their hypothalamic interactions in food intake regulation could open new frontiers for effective pharmacological therapeutic approach to Obesity and other nutritional disorders

Metabolic Disorders in Elderly Patients with Hematologic Malignancies. A Review

Over recent decades, due to the gradual rise in life expectancy and the consequent aging of the population, the incidence of some hematological malignancies most common in the elderly is expected to increase. In elderly cancer patients, the older age is an adverse prognostic factor because of specific age-related conditions, such as changes in cellular biology and reduced functional reserve in multiple organ systems, as well as in consequence of comorbidities. Some age-related pathological conditions, such as diabetes mellitus, renal failure, chronic obstructive pulmonary disease, cardiovascular dysfunction, liver disease and other disorders may predispose the elderlies to develop metabolic abnormalities. In the elderly, the occurrence of hematological malignancies can cause some metabolic disorders or worsen pre-existing dysmetabolic conditions that increase the outcomes of these patients. Hyperuricemia is the most common metabolic abnormality; hyperuricemia less commonly may be associated with hyperkalemia, hyperphosphatemia and hypocalcemia, in the framework of oncologic emergency that is the Tumor lysis syndrome. Hypercalcemia is relatively common in patients with multiple myeloma and adult T-cell Lymphoma. Cases of Syndrome of inappropriate secretion of antidiuretic hormone (SIADH) in patients with hematological malignancies have also been reported. Idiopathic hyperammonemia may occur in oncohematological patients after receiving intensive chemotherapy or following bone marrow transplantation. Moreover, there is evidence that patients with lymphoma, leukemia and multiple myeloma can develop Type B lactic acidosis. Non–islet cell tumor hypoglycemia and Hyperglycemia are other potential metabolic abnormalities occurring in patients with hematological malignancies. The pathogenesis of these metabolic disorders is often unclear and several theories have been postulated; possible mechanisms include: increase in neoplastic cell turnover and apoptosis, blast crisis, cytotoxic effects of chemotherapy, tumor secretion of hormones, peptides or cytokines, immune cross-reactivity between malignant and normal tissues, malignancy-induced enzyme dysfunction. Parenteral nutrition, sarcopenia, cachexia, stress, immune deficiency and infections could contribute. Although successful treatment of the underlying tumor often improves metabolic disorders, these conditions often worse prognosis and are associated with poor survival; thus it is important to consider early detection and effective treatment

Multifaceted enrichment analysis of RNA-RNA crosstalk reveals cooperating micro-societies in human colorectal cancer

Alterations in the balance of mRNA and microRNA (miRNA) expression profiles contribute to the onset and development of colorectal cancer. The regulatory functions of individual miRNA-gene pairs are widely acknowledged, but group effects are largely unexplored. We performed an integrative analysis of mRNA–miRNA and miRNA–miRNA interactions using high-throughput mRNA and miRNA expression profiles obtained from matched specimens of human colorectal cancer tissue and adjacent non- tumorous mucosa. This investigation resulted in a hypernetwork-based model, whose functional back- bone was fulfilled by tight micro-societies of miR- NAs. These proved to modulate several genes that are known to control a set of significantly enriched cancer-enhancer and cancer-protection biological processes, and that an array of upstream regulatory analyses demonstrated to be dependent on miR-145, a cell cycle and MAPK signalling cascade master regulator. In conclusion, we reveal miRNA-gene clusters and gene families with close functional relationships and highlight the role of miR-145 as potent upstream regulator of a complex RNA–RNA crosstalk, which mechanistically modulates several signalling path- ways and regulatory circuits that when deranged are relevant to the changes occurring in colorectal carcinogenesis

MicroRNA co-expression networks exhibit increased complexity in pancreatic ductal compared to Vater’s papilla adenocarcinoma

iRNA expression abnormalities in adenocarcinoma arising from pancreatic ductal system (PDAC) and Vater’s papilla (PVAC) could be associated with distinctive pathologic features and clinical cancer behaviours. Our previous miRNA expression profiling data on PDAC (n=9) and PVAC (n=4) were revaluated to define differences/ similarities in miRNA expression patterns. Afterwards, in order to uncover target genes and core signalling pathways regulated by specific miRNAs in these two tumour entities, miRNA interaction networks were wired for each tumour entity, and experimentally validated target genes underwent pathways enrichment analysis. One hundred and one miRNAs were altered, mainly over-expressed, in PDAC samples. Twenty-six miRNAs were deregulated in PVAC samples, where more miRNAs were down-expressed in tumours compared to normal tissues. Four miRNAs were significantly altered in both subgroups of patients, while 27 miRNAs were differentially expressed between PDAC and PVAC. Although miRNA interaction networks were more complex and dense in PDAC than in PVAC, pathways enrichment analysis uncovered a functional overlapping between PDAC and PVAC. However, shared signalling events were influenced by different miRNA and/or genes in the two tumour entities. Overall, specific miRNA expression patterns were involved in the regulation of a limited core signalling pathways in the biology landscape of PDAC and PVAC

Focus on Pitavastatin

Currently, different statins are available for the treatment of dyslipidemia: Atorvastatin, Simvastatin, Rosuvastatin, Lovastatin, Pravastatin, and Fluvastatin; the newest entry in this class of drugs is Pitavastatin.The purpose of the present study was to examine the latest evidences on Pitavastatin, more than 10 years after its first marketing and focuses on the most recent evidence regarding its differences with other available statins. A literature review of the last 3 years (January 2013 - January 2016) has been carried out via Pub Med. 193 obtained items were analysed.Pitavastatin has been studied against other drugs in its class and has demonstrated high potency in reducing LDL-Cholesterol levels and increasing HDL-Cholesterol. Pitavastatin has demonstrated a significant reduction in atherosclerotic plaque volumes and several pleiotropic effects, which suggest its potential benefits in reducing cardiovascular risk.At present, Pitavastatin don’t seem to have adverse effects on glucose metabolism; it has no adverse effects on renal function and currently there is no clinical evidence of Pitavastatin-induced hepatotoxicity. Pitavastatin has favorable pharmacokinetic and safety profiles and its characteristic structure provides significant efficacy at low doses

The electronic structure and dynamics of the excited triplet state of octaethylaluminum(III)-porphyrin investigated with advanced EPR methods

The photoexcited triplet state of octaethylaluminum(III)-porphyrin (AlOEP) was investigated by time-resolved Electron Paramagnetic Resonance, Electron Nuclear Double Resonance and Electron Spin Echo Envelope Modulation in an organic glass at 10 and 80 K. This main group element porphyrin is unusual because the metal has a small ionic radius and is six-coordinate with axial covalent and coordination bonds. It is not known whether triplet state dynamics influence its magnetic resonance properties as has been observed for some transition metal porphyrins. Together with density functional theory modelling, the magnetic resonance data of AlOEP allow the temperature dependence of the zero-field splitting (ZFS) parameters, D and E, and the proton AZZ hyperfine coupling (hfc) tensor components of the methine protons, in the zero-field splitting frame to be determined. The results provide evidence that the ZFS, hfc and spin–lattice relaxation are indeed influenced by the presence of a dynamic process that is discussed in terms of Jahn-Teller dynamic effects. Thus, these effects should be taken into account when interpreting EPR data from larger complexes containing AlOEP