Metronomic Chemotherapy with Vinorelbine Produces Clinical Benefit and Low Toxicity in Frail Elderly Patients Affected by Advanced Non-Small Cell Lung Cancer

Lung cancer is the leading cause of death worldwide. The treatment choice for advanced stage of lung cancer may depend on histotype, performance status (PS), age, and comorbidities. In the present study, we focused on the effect of metronomic vinorelbine treatment in elderly patients with advanced unresectable non-small cell lung cancer (NSCLC). Methods. From January 2016 to December 2016, 44 patients affected by non-small cell lung cancer referred to our oncology day hospital were progressively analyzed. The patients were treated with oral vinorelbine 30 mg x 3/wk or 40 mg x 3/wk meaning one day on and one day off. The patients were older than 60, stage IIIB or IV, ECOG PS ≥ 1, and have at least one important comorbidity (renal, hepatic, or cardiovascular disease). The schedule was based on ECOG-PS and comorbidities. The primary endpoint was progression-free survival (PFS). PFS was used to compare patients based on different scheduled dosage (30 or 40 mg x3/weekly) and age (more or less than 75 years old) as exploratory analysis. We also evaluated as secondary endpoint toxicity according to Common Toxicity Criteria Version 2.0. Results. Vinorelbine showed a good safety profile at different doses taken orally and was effective in controlling cancer progression. The median overall survival (OS) was 12 months. The disease control rate (DCR) achieved 63%. The median PFS was 9 months. A significant difference in PFS was detected comparing patients aged below with those over 75, and the HR value was 0.72 (p<0.05). Not significant was the difference between groups with different schedules. Conclusions. This study confirmed the safety profile of metronomic vinorelbine and its applicability for patients unfit for standard chemotherapies and adds the possibility of considering this type of schedule not only for very elderly patients

Effect of soil management and training system on negroamaro wine aroma

This study aimed to assess the impact of two soil managements and training systems on yield and wine aroma compounds of Negroamaro variety grown in a warm climate region (southern Italy). Cover crop (CC) and soil tillage (ST) as soil management, whilst bilateral Guyot (BG) and monolateral Guyot (MG) as training systems were compared. Free and bound volatile fractions were evaluated by GC-MS. ST and CC as well as BG and MG significantly affected yield parameters. In particular, yield was higher in ST and BG than in CC and MG, respectively; moreover, it was found to be positively influenced by interaction between BG and ST. Regarding aroma compounds, significant interactions between soil management and training system factors were observed. In case of free volatiles, the most positive interaction was found between BG and ST, whereas, for bound volatiles, the best interaction was represented by MG with both soil tillage and cover crop. Vine leaf area and development over vine growth stages along with water stress levels played an important role in determining the aroma profile as well as yield parameters. In conclusion, the training system significantly interacted with soil management and affected most of important aroma compounds in Negroamaro wine

A brief review about anxiety and aggressive behavior in pediatric age

Anxiety can be considered a normal experience of the human being and as such also of the child. It manifests itself in different ways according to the level of development: in the smaller the child, the more anxiety is expressed with manifestations that involve the whole organism, becoming evident either with motor excitement or with physical discomfort. As the psychic apparatus is structured, anxiety is experienced as an inner phenomenon and is experienced as an unpleasant state. Fortunately, we are all a bit anxious, even if there are some people who are more, others less

Psychopathological and psychodynamic hypotheses for pediatric stuttering

Stuttering is a common language alteration in pediatric age consisting in repetitions and blocks, which entail a break in the rhythm and melody of the speech. According to the WHO it is a disorder of the rhythm of the word, the subject knows precisely what he would like to say, but at the same time he is not able to say it. It is a great inconvenience for those affected, also because the slowing down of speaking is not about thought or cognitive skills

Acetaldehyde binding energies: a coupled experimental and theoretical study

Acetaldehyde is one of the most common and abundant gaseous interstellar complex organic molecules, found in cold and hot regions of the molecular interstellar medium. Its presence in the gas-phase depends on the chemical formation and destruction routes, and its binding energy (BE) governs whether acetaldehyde remains frozen onto the interstellar dust grains or not. In this work, we report a combined study of the acetaldehyde BE obtained via laboratory TPD (Temperature Programmed Desorption) experiments and theoretical quantum chemical computations. BEs have been measured and computed as a pure acetaldehyde ice and as mixed with both polycrystalline and amorphous water ice. Both calculations and experiments found a BE distribution on amorphous solid water that covers the 4000--6000 K range, when a pre-exponential factor of $1.1\times 10^{18}s^{-1}$ is used for the interpretation of the experiments. We discuss in detail the importance of using a consistent couple of BE and pre-exponential factor values when comparing experiments and computations, as well as when introducing them in astrochemical models. Based on the comparison of the acetaldehyde BEs measured and computed in the present work with those of other species, we predict that acetaldehyde is less volatile than formaldehyde, but much more than water, methanol, ethanol, and formamide. We discuss the astrochemical implications of our findings and how recent astronomical high spatial resolution observations show a chemical differentiation involving acetaldehyde, which can easily explained as due to the different BEs of the observed molecules.Comment: 12 pages, 6 figure

Highly efficient synthesis of the tricyclic core of Taxol by cascade metathesis

An efficient enantioselective synthesis of the ABC tricyclic core of the anticancer drug Taxol is reported. The key step of this synthesis is a cascade metathesis reaction, which leads in one operation to the required tricycle if appropriate fine-tuning of the dienyne precursor is performed

Breast tumor cell invasion and pro-invasive activity of cancer-associated fibroblasts co-targeted by novel urokinase-derived decapeptides

Among peritumoral cells, cancer-associated fibroblasts (CAFs) are major facilitators of tumor progression. This study describes the effects of two urokinase-derived, novel decapeptides, denoted as Pep 1 and its cyclic derivative Pep 2. In a mouse model of tumor dissemination, using HT1080 fibrosarcoma cells, Pep 2 reduced the number and size of lung metastases. Specific binding of fluoresceinated Pep 2 to HT1080 and telomerase immortalised fibroblasts (TIF) cell surfaces was enhanced by αv overexpression or abolished by excess vitronectin, anti-αv antibodies or silencing of ITGAV αv gene, identifying αv-integrin as the Pep 2 molecular target. In 3D-organotypic assays, peptide-exposed TIFs and primary CAFs from breast carcinoma patients both exhibited a markedly reduced pro-invasive ability of either HT1080 fibrosarcoma or MDA-MB-231 mammary carcinoma cells, respectively. Furthermore, TIFs, either exposed to Pep 2, or silenced for αv integrin, were impaired in their ability to chemoattract cancer cells and to contract collagen matrices, exhibiting reduced α-smooth muscle actin (α-SMA) levels. Finally, peptide exposure of αv-expressing primary CAFs led to the downregulation of α-SMA protein and to a dramatic reduction of their pro-invasive capability. In conclusion, the ability of the novel decapeptides to interfere with tumor cell invasion directly and through the down-modulation of CAF phenotype suggests their use as lead compounds for co-targeting anti-cancer strategies