Therapeutic sequences in patients with grade 1−2 neuroendocrine tumors (NET): an observational multicenter study from the ELIOS group

Purpose: Many different treatments are suggested by guidelines to treat grade 1−2 (G1−G2) neuroendocrine tumors (NET). However, a precise therapeutic algorithm has not yet been established. This study aims at identifying and comparing the main therapeutic sequences in G1−G2 NET. Methods: A retrospective observational Italian multicenter study was designed to collect data on therapeutic sequences in NET. Median progression-free survival (PFS) was compared between therapeutic sequences, as well as the number and grade of side effects and the rate of dose reduction/treatment discontinuation. Results: Among 1182 patients with neuroendocrine neoplasia included in the ELIOS database, 131 G1–G2 gastroenteropancreatic, lung and unknown primary NET, unresectable or persistent/relapsing after surgery, treated with ≥2 systemic treatments, were included. Four main therapeutic sequences were identified in 99 patients: (A) somatostatin analogs (SSA) standard dose to SSA high dose (n = 36), (B) SSA to everolimus (n = 31), (C) SSA to chemotherapy (n = 17), (D) SSA to peptide receptor radionuclide therapy (PRRT) (n = 15). Median PFS of the second-line treatment was not reached in sequence A, 33 months in sequence B, 20 months in sequence C, 30 months in sequence D (p = 0.16). Both total number and severity of side effects were significantly higher in sequences B and C than A and D (p = 0.04), as well as the rate of dose reduction/discontinuation (p = 0.03). Conclusions: SSA followed by SSA high dose, everolimus, chemotherapy or PRRT represent the main therapeutic sequences in G1−G2 NET. Median PFS was not significantly different between sequences. However, the sequences with SSA high dose or PRRT seem to be better tolerated than sequences with everolimus or chemotherapy

Field emission properties of as-grown multiwalled carbon nanotube films

Multiwalled carbon nanotubes have been produced by ethylene catalytic chemical vapor deposition and used to fabricate thick and dense freestanding films ("buckypapers") by membrane filtering. Field emission properties of buckypapers have been locally studied by means of high vacuum atomic force microscopy with a standard metallic cantilever used as anode to collect electrons emitted from the sample. Buckypapers showed an interesting linear dependence in the Fowler-Nordheim plots demonstrating their suitability as emitters. By precisely tuning the tip-sample distance in the submicron region we found out that the field enhancement factor is not affected by distance variations up to 2um. Finally, the study of current stability showed that the field emission current with intensity of about 3,3*10-5A remains remarkably stable (within 5% fluctuations) for several hours.Comment: 18 pages, 5 figure

Quenched BKB_K-parameter with the Wilson and Clover actions at β=6.0\beta = 6.0

We present results for the Kaon $B$ parameter from a sample of $200$ configurations using the Wilson action and $460$ configurations using the Clover action, on a $18^3 \times 64$ lattice at $\beta=6.0$. A slight improvement of the chiral behaviour of $B_K$ is observed due to the Clover action. We have also compared the results for $B_K$ obtained from two different procedures for the boosting of the coupling constant $g$. We observe a strong dependence of $B_K$ on the prescription adopted for $g$ in the Wilson case, contrary to the results of the Clover case which are almost unaffected by the choice of $g$. Combining some recently obtained non perturbative estimates for the renormalisation constants with our Clover matrix element, we observe a significant improvement in the chiral behaviour of $B_K$.Comment: 3 pages, Latex, Postscript file with figures available at ftp://hpteo.roma1.infn.it/pub/preprints/lat94/donini ; to appear in Lattice '94, Nucl. Phys. (Proc.Suppl.

Twenty-Seven Y-Chromosome Short Tandem Repeats Analysis of Italian Mummies of the 16th and 18th Centuries: An Interdisciplinary Research

Roccapelago (MO) is a small village located in the Northern Central Apennines, with a population of 31 inhabitants (2014). In 2010, more than 400 individuals dated between the end of the 16th and the 18th century, many of which partially mummified, were discovered in the crypt of the church. This small village, because of its geographical location and surrounding environment, seems to possess the characteristics of a genetic isolate, useful for population genetics and genealogical analyses. Thus, a diachronic study of DNA aimed at investigating the structure and dynamics of the population of Roccapelago over the about 4 centuries, was conducted by analyzing ancient and modern inhabitants of the village. The 14 modern samples were selected by considering both the founder surnames of the village, identified thanks to the study of parish registers, and the grandparent’s criterion. From 25 ancient mummies, morphologically assigned to male individuals, the petrous bone, that harbors high DNA amounts, was selected for the DNA extraction. The quantification and qualitative assessment of total human male DNA were evaluated by a real-time PCR assay using the Quantifiler Trio DNA Quantification Kit and multiplex PCR of 27 Y-chromosome short tandem repeat (Y-STR) markers included in the Yfiler Plus PCR Amplification Kit, with seven rapidly mutating Y-STR loci for improving discrimination of male lineages, was performed to genotype the samples. Y-STRs were analyzed according to the criteria of ancient DNA (aDNA) analysis to ensure that authentic DNA typing results were obtained from these ancient samples. The molecular analysis showed the usefulness of the Y chromosome to identify historically relevant remains and discover patterns of relatedness in communities moving from anthropology to genetic genealogy and forensics

Superconducting properties of Nb thin films deposited on porous silicon templates

Porous silicon, obtained by electrochemical etching, has been used as a substrate for the growth of nanoperforated Nb thin films. The films, deposited by UHV magnetron sputtering on the porous Si substrates, inherited their structure made of holes of 5 or 10 nm diameter and of 10 to 40 nm spacing, which provide an artificial pinning structure. The superconducting properties were investigated by transport measurements performed in the presence of magnetic field for different film thickness and substrates with different interpore spacing. Perpendicular upper critical fields measurements present peculiar features such as a change in the H_c2(T) curvature and oscillations in the field dependence of the superconducting resistive transition width at H=1 Tesla. This field value is much higher than typical matching fields in perforated superconductors, as a consequence of the small interpore distance.Comment: accepted for publication on Journal of Applied Physic

A New Family of Jumonji C Domain-Containing KDM Inhibitors Inspired by Natural Product Purpurogallin

Aberrant epigenetic modifications are involved in cancer development. Jumonji C domain-containing histone lysine demethylases (KDMs) are found mainly up-regulated in breast, prostate, and colon cancer. Currently, growing interest is focusing on the identification and development of new inhibitors able to block the activity of KDMs and thus reduce tumor progression. KDM4A is known to play a role in several cellular physiological processes, and was recently found overexpressed in a number of pathological states, including cancer. In this work, starting from the structure of purpurogallin 9aa, previously identified as a natural KDM4A inhibitor, we synthesized two main sets of compound derivatives in order to improve their inhibitory activity against KDM4A in vitro and in cells, as well as their antitumor action. Based on the hypothetical biogenesis of the 5-oxo-5H-benzo[7]annulene skeleton of the natural product purpurogallin (Salfeld, 1960; Horner et al., 1961; Dürckheimer and Paulus, 1985; Tanaka et al., 2002; Yanase et al., 2005) the pyrogallol and catechol units were first combined with structural modifications at different positions of the aryl ring using enzyme-mediated oxidative conditions, generating a series of benzotropolone analogs. Two of the synthetic analogs of purpurogallin, 9ac and 9bc, showed an efficient inhibition (50 and 80%) of KDM4A in enzymatic assays and in cells by increasing levels of its specific targets, H3K9me3/2 and H3K36me3. However, these two compounds/derivatives did not induce cell death. We then synthesized a further set of analogs of these two compounds with greater structural diversification. The most potent of these analogs, 9bf, displayed the highest KDM4A inhibitory enzymatic activity in vitro (IC50 of 10.1 and 24.37 μM) in colon cancer cells, and the strongest antitumor action in several solid and hematological human cancer cell lines with no toxic effect in normal cells. Our findings suggest that further development of this compound and its derivatives may lead to the identification of new therapeutic antitumor agents acting through inhibition of KDM4A

Haplotype data and forensic evaluation of 23 Y-STR and 12 X-STR loci in eight ethnic groups from Eritrea

Eritrea is a multi-ethnic country of over 3 million of people consisting of different ethnic groups, having each its own language and cultural tradition. Due to the lack of population genetic data for markers of forensic interest, in this study, we analyzed the genetic polymorphisms of 23 Y-chromosome STR loci and of 12 X-chromosome STR loci in a sample of 255 unrelated individuals from 8 Eritrean ethnic groups, with the aim to generate a reference haplotype database for anthropological and forensic applications. X- and Y-chromosomes markers may indeed offer information especially in personal identification and kinship testing, when relying on the availability of large local population data to derive sufficiently accurate frequency estimates. The population genetic analyses in the Eritrean sample for both the two set of Y- and X-STR markers showed high power of discrimination both at country-based and population levels. Comparison population results highlight the importance of considering the ethnic composition within the analyzed country and the necessity of increasing available data especially when referring to heterogeneous populations such as the African ones