A phase I clinical and pharmacological study evaluating vinflunine in combination with doxorubicin as first line treatment in metastatic breast cancer

Vinfunine (VFL) is a novel bifluorinated tubulin-targeted agent of the vinca alkaloids class active in advanced stage breast cancer. We conducted a phase I study combining VFL with doxorubicin (DXR) to define the recommended dose (RD), safety, pharmacokinetic (PK) interaction and efficacy. Two schedules (day 1 every 3weeks; days 1 and 8 every 3weeks) were investigated as first line chemotherapy in metastatic breast cancer patients. Thirty-two patients received a total of 162 cycles of the VFL-DXR combination (median 6). The RDs were VFL 250mg/m2/DXR 40mg/m2 every 3weeks for schedule 1 and VFL 120mg/m2/DXR 25mg/m2 days 1 and 8 every 3weeks for schedule 2. The main dose-limiting toxicity was neutropenia. The most frequent non-hematological adverse events were nausea, fatigue, constipation, vomiting, anorexia, stomatitis and dyspnea. Objective response rate was reached in 47.1% of the patients. No PK interaction was observed. VFL-DXR combination is feasible with manageable toxicity. The antitumor activity was promising and supports further evaluatio

Exploiting lipid and polymer nanocarriers to improve the anticancer sonodynamic activity of chlorophyll

Sonodynamic therapy is an emerging approach that uses low-intensity ultrasound to activate a sonosensitizer agent triggering its cytotoxicity for selective cancer cell killing. Several molecules have been proposed as sonosensitizer agents, but most of these, as chlorophyll, are strongly hydrophobic with a low selectivity towards cancer tissues. Nanocarriers can help to deliver more efficiently the sonosensitizer agents in the target tumor site, increasing at the same time their sonodynamic effect, since nanosystems act as cavitation nuclei. Herein, we propose the incorporation of unmodified plant-extracted chlorophyll into nanocarriers with different composition and structure (i.e., liposomes, solid lipid nanoparticles and poly(lactic-co-glycolic acid) nanoparticles) to obtain aqueous formulations of this natural pigment. The nanocarriers have been deeply characterized and then incubated with human prostatic cancer cells (PC-3) and spheroids (DU-145) to assess the influence of the different formulations on the chlorophyll sonodynamic effect. The highest sonodynamic cytotoxicity was obtained with chlorophyll loaded into poly(lactic-co-glycolic acid) nanoparticles, showing promising results for future clinical investigations on sonodynamic therapy

SWCNT-porphyrin nano-hybrids selectively activated by ultrasound: an interesting model for sonodynamic applications

Sonodynamic therapy (SDT) is an innovative anticancer approach, based on the excitation of a given molecule (usually a porphyrin) by inertial acoustic cavitation that leads to cell deathviathe production of reactive oxygen species (ROS). This study aims to prepare and characterize nanosystems based on porphyrin grafted carbon nanotubes (SWCNTs), to understand some aspects of the mechanisms behind the SDT phenomenon. Three different porphyrins have been covalently linked to SWCNTs using either Diels-Alder or 1,3-dipolar cycloadditions. ROS production and cell viability have been evaluated upon ultrasound irradiation. Despite the low porphyrin content linked on the SWCNT, these systems have shown high ROS production and high tumour-cell-killing ability. The existence of a PET (photoinduced electron transfer)-like process would appear to be able to explain these observations. Moreover, the demonstrated ability to absorb light limits the impact of side effects due to light-excitation

Heptavalent Pneumococcal Conjugate Vaccine: growing knowledge and its implications for Italy

Introductive note A wide literature on Streptococcus Pneumoniae (Pn) infections is available, largely published in the recent years, after the introduction of the heptavalent conjugate vaccine in US and in Europe. This review is based on the most up-to-date scientific articles about this pathogen

Assessment of knowledge, attitudes, and propensity towards HPV vaccine of young adult students in Italy

Background: Human Papillomavirus (HPV) is a common sexually transmitted infection (STI), representing the main cause of genital warts and cervical cancer. This cross-sectional study evaluated knowledge and attitudes about HPV infection, related diseases, and prevention and propensity towards HPV vaccine among undergraduate students. Methods: An online and written survey about HPV and its prevention, targeted to young adults of both genders, was addressed to students attending health sciences and other schools at Universities of Genoa and Bari. Results: The overall median knowledge and attitude scores were 56.3% (25\u201375 p = 40\u201368.8%) and four out of five (25\u201375 p = 4\u20135), respectively. In the multivariate analysis, attending a health sciences university, using social networks 642 h a day, a history of STI, having heard about HPV and HPV vaccine previously resulted as predictors of higher knowledge scores. Having heard about HPV previously also predicted a high attitude score, together with a perceived economic status as good. Having Italian and healthcare worker parents, being employed, and following a specific diet, instead, predicted lower attitude score. Conclusions: Poor knowledge and good attitudes were found among undergraduates about HPV. In order to increase HPV vaccine compliance and the counselling skills of future healthcare workers, the improvement of training on HPV is needed

Phytosociological analysis of restored and managed grassland habitat within an urban national park

Floyd Bennett Field (FBF), 579 ha in extent, is a division of Gateway National Recreation Area. It is the site of a former airfield, constructed by filling salt marshes with dredged materials. Except for the portion known locally as the “North Forty,” all sections of FBF have been cut over to maintain low vegetation. A grassland management plan (GRAMP) for 165 ha was initiated in 1986, to maintain habitats for open-country birds. Over the next few years, encroaching woody vegetation was removed manually and mechanically from the management area. Since then, it has been maintained as a grassland and receives annual mowing, as well as continued manual removal of the larger woody sprouts. A portion of the GRAMP management area (III) was selected for intensive study of vegetation composition. A grid system was created and vegetation cover was estimated in 127, 1 m × 1 m quadrats. The quadrats were subjected to cluster analysis (CA). Eleven clusters were recognized. These clusters were treated as “plant associations.” The following types were distinguished: (native) little bluestem–dewberry grassland, six-weeks fescue annual grassland, a grass marsh, a rush marsh, a switchgrass dry grassland, and a deer-tongue panicgrass grassland; (exotic) mugwort herbland, oriental bittersweet-Japanese honeysuckle vineland, Kentucky bluegrass-mixed grassland, Japanese knotweed tall herbland, and spotted knapweed-common St. Johnswort herbland. The little bluestem–dewberry association accounted for nearly half of all quadrats; six subclusters were recognized. The plant associations determined by CA were compared with plant lists compiled during traverses of all of the map categories in the six GRAMP Areas (I, II, III, IV, V, VI). A table was created to relate the quantitative data of the plant associations to the appropriate map categories. A nonmetric multidimensional scaling ordination (NMDS) was performed on the quadrat data. Finally, the plant associations were compared with those described in the literature of local vegetation studies. The mowing program has been effective in decreasing woody plant cover and has permitted the invasion of a few taxa into monospecific communities, but attendant disturbance of the substrate is likely to cause an increase in exotic plant taxa. As earlier studies noted, mowing has caused the increase in cover of sod-forming grass, and bare ground has virtually disappeared in the managed area. This has negative implications for the maintenance of those grassland bird species that require open ground for nesting

Performance testing of two new one-step real time PCR assays for detection of human influenza and avian influenza viruses isolated in humans and Respiratory Syncytial Virus

Introduction and Methods. Two real time one-step RT-PCRassays were developed for simultaneous detection and typingof influenza A and B viruses and detection of Respiratory Syncytial Virus (RSV). As regard influenza, primers were designedto amplify specific sequences of gene M of A/H1N1, A/H3N2,A/H5N1, A/H7N7 and A/H9N2 viruses and of gene NP of typeB viruses belonging both Yamagata and Victoria lineage. Specificity, analytical and clinical sensitivity, dynamic range, linearity of the new assays were evaluated.Results. Dynamic ranges for Influenza A and B, and RSV,were at least five logs and linearity was conserved. In orderto evaluate the specificity, 80 nasopharyngeal swabs resulting Influenza and RSV negative by multiplex nested PCR andcell culture, were tested and 79 resulted negative. The detection limits for influenza A and B, calculated by 95% probit,was 0,008 and 0,09 PFU, respectively, resulting more sensible than nested PCR. A total of 75 specimens (10 A/H1N1,