Adrenomedullin in Ovarian Cancer: Foe In Vitro and Friend In Vivo?

Stromal elements within a tumor interact with cancer cells to create a microenvironment that supports tumor growth and survival. Adrenomedullin (ADM) is an autocrine/paracrine factor produced by both stromal cells and cancer cells to create such a microenvironment. During differentiation of macrophages, ADM is produced in response to pro-inflammatory stimuli and hypoxia. In this study we investigated the role of ADM as a growth factor for ovarian cancer cells and as a modulator of macrophages. We also analyzed ADM expression levels in a retrospective clinical study using nanofluidic technology and assessment of ADM at the gene level in 220 ovarian cancer patients. To study the effects of ADM, ovarian cancer cell lines A2780, OVCAR-3, and HEY and their drug-resistant counterparts were used for proliferation assays, while monocytes from healthy donors were differentiated in vitro. ADM was a weak growth factor, as revealed by proliferation assays and cell cycle analysis. After culturing cancer cells under stressing conditions, such as serum starvation and/or hypoxia, ADM was found to be a survival factor in HEY but not in other cell lines. In macrophages, ADM showed activity on proliferation/differentiation, primarily in type 2 macrophages (M2). Unexpectedly, the clinical study revealed that high expression of ADM was linked to positive outcome and to cancer with low Ca125. In conclusion, although in vitro ADM was a potential factor in biological aggressiveness, this possibility was not confirmed in patients. Therefore, use of an ADM antagonist would be inappropriate in managing ovarian cancer patients.     

Adoptive immunotherapy with cytokine-induced killer cells generated with a new good manufacturing practice-grade protocol

Background aimsWe have recently shown that thymoglobulin (TG) efficiently expands cytokine-induced killer (CIK) cells in combination with interferon (IFN)-γ and interleukin (IL)-2 (ITG2 protocol). It is presently unknown whether the infusion of autologous immune effector cells generated by TG, IFN-γ and IL-2 is feasible and safeMethodsFive patients with advanced and/or refractory solid tumors were enrolled in the present phase I/II study. Peripheral blood mononuclear cells (PBMC) collected by leukapheresis were stimulated under good manufacturing practice (GMP)-conditions with IFN-γ, followed by TG and IL-2. After 2–3 weeks in culture, a median of 4.65 × 10⁶ immune effector cells per kilogram of recipient's body weight was obtained and infused intravenously. The median time from enrollment into the study to infusion of the expanded CIK cells was 30 daysResultsITG2 efficiently expanded immune effector cells that comprised both conventional natural killer (NK) cells and CD3⁺ CD16⁺ CD56⁺ CIK cells. One patient with advanced melanoma died because of disease progression before the infusion of CIK cells. The target dose of at least 2.5 × 10⁶ CIK cells/kg of recipient's body weight was reached in four out of five evaluable patients. CIK cells were administered intravenously without any measurable toxicity. In vitro, CIK cells exerted lytic activity against cervical cancer cells. The median survival was 4.5 months (range 1–13) from the first infusion of CIK cells.ConclusionsThis study has highlighted the feasibility and safety of the administration of CIK cells generated with the ITG2 protocol. Whether CIK cells can help control disease burden in patients with advanced malignancies will be determined in future clinical trials.     

g<Emphasis FontCategory="NonProportional">raphite</Emphasis> - a Bioconductor package to convert pathway topology to gene network

Background  

Gene set analysis is moving towards considering pathway topology as a crucial feature. Pathway elements are complex entities such as protein complexes, gene family members and chemical compounds. The conversion of pathway topology to a gene/protein networks (where nodes are a simple element like a gene/protein) is a critical and challenging task that enables topology-based gene set analyses.     

Seasonality of marriages in sardinian pastoral and agricultural communities in the nineteenth century

The study of marriage seasonality of populations with different socioeconomic backgrounds may contribute to the better understanding their reproductive behaviours. This study analyses the monthly distribution of marriages in the 19th century in four agricultural villages and four pastoral villages on the island of Sardinia (Italy). The data were derived from 7340 marriage acts (3571 for the four agricultural villages and 3769 for the four pastoral villages). The aim is to ascertain whether the Sardinian agricultural and pastoral communities followed the matrimonial models reported for contemporary Italy and Europe and whether there was a change in the monthly distribution of marriages between the two halves of the 19th century. The results suggest that the marriage seasonality of the Sardinian farmers and shepherds was very similar to the patterns shown in the 19th century by Italian and European agricultural and pastoral communities. The Sardinian farmers preferred to marry in autumn-winter, while the Sardinian shepherds had a very high concentration of marriages in summer-autumn. Both communities avoided marriages in the Advent and Easter periods and in the month of May (dedicated to the Virgin Mary), and the farmers also in August (also dedicated to the Virgin Mary). Despite a certain seasonal stability, there was a significant change in the monthly distribution of marriages between the two halves of the 19th century in both the agricultural and pastoral communities, probably due to a series of laws that transformed the centuries-old socioeconomic system of Sardinia in the second half of the century.     

The applicability of an amidated polysaccharide hydrogel as a cartilage substitute: structural and rheological characterization

An amidic derivative of a carboxymethylcellulose-based hydrogel was obtained and characterized in terms of amidation degree. NMR studies and FT-IR imaging spectroscopy demonstrated that the reaction allowed a polymer to be obtained that was characterized by a regular distribution of amidic groups along the polysaccharide chains. Through this regularity, a homogenous three-dimensional scaffold was obtained, which maintained the thixotropic property of the linear polysaccharide.     

Organization and Regulation of meta Cleavage Pathway Genes for Toluene and o-Xylene Derivative Degradation in Pseudomonas stutzeri OX1

Pseudomonas stutzeri OX1 meta pathway genes for toluene and o-xylene catabolism were analyzed, and loci encoding phenol hydroxylase, catechol 2,3-dioxygenase, 2-hydroxymuconate semialdehyde dehydrogenase, and 2-hydroxymuconate semialdehyde hydrolase were mapped. Phenol hydroxylase converted a broad range of substrates, as it was also able to transform the nongrowth substrates 2,4-dimethylphenol and 2,5-dimethylphenol into 3,5-dimethylcatechol and 3,6-dimethylcatechol, respectively, which, however, were not cleaved by catechol 2,3-dioxygenase. The identified gene cluster displayed a gene order similar to that of the Pseudomonas sp. strain CF600 dmp operon for phenol catabolism and was found to be coregulated by the tou operon activator TouR. A hypothesis about the evolution of the toluene and o-xylene catabolic pathway in P. stutzeri OX1 is discussed.     

Apport de l’injection intracaverneuse de Prostaglandine E1 lors de la premiere consultation de l’impuissant: à propos de 414 cas

The authors report their experience of 414 injections of prostaglandin E1 (prostine). The diagnostic orientation between functional or organic impotence was assessed through questionaires and more particularly on the presence or absence of nocturnal or morning erections. The prostine reconditioning and self injection use techniques are precised: 80% of positive responses with better results in the oldest patients, whatever their medical antecedents. No relation between positive response to prostaglandin E1 and normal nocturnal erections could be found. Patients still presenting erections can present good or bad responses. This confirms the results previously given only allow us to put in evidence the good functional and anatomic state of cavernous bodies, without any etiological orientation (not mentioning the cases in which these self-injections reveal the presence of deformation, bend or fibrosis). The acceptance of self injection is low (30%) as well as a regular and prolonged medical observance (only 15%). This work confirms the low rate of local complications after repeated injections and the low rate of prolonged erections or priapism during Test 1. However, these possibilities must incite to prudence as for the generalization of this kind of treatment, out of specialized centers.     

Cognitive Modulation of Psychophysical,Respiratory and Autonomic Responses to Cold Pressor Test

In healthy subjects with high hypnotisability (highs) under hypnosis, subjectively effective suggestions for analgesia abolish the increases in blood pressure associated with cold pressor test (cpt) by reducing the peripheral vascular resistance. The aim of the present study was to investigate the effects of the suggestions of analgesia on the responses to cpt in healthy highs (n = 22) and in low hypnotisable participants (lows, n = 22) out of hypnosis. Cpt was administered without (CPT) and with suggestions for analgesia (CPT+AN). Psychophysical (pain intensity, pain threshold, cpt duration (time of immersion) and pain tolerance, defined as the difference between cpt duration and pain threshold), respiratory (amplitude and frequency) and autonomic variables (tonic skin conductance, mean RR interval (RR = 1/heart rate), blood pressure, skin blood flow) were studied. The suggestions for analgesia increased cpt duration and RR in both groups, but decreased pain intensity and enhanced pain threshold only in highs; in both groups they did not modulate systolic blood pressure, tonic skin conductance and skin blood flow; thus, increased parasympathetic activity appears responsible for the heart rate reduction induced by suggestions in both groups. In conclusion, our findings show that suggestions modulate pain experience differentially in highs and lows, and are partially effective also in lows. We hypothesize that the mechanisms responsible for the efficacy of suggestions in healthy lows may be involved also in their efficacy in chronic pain patients with low hypnotisability.