University of Turin

About: University of Turin is a education organization based out in Turin, Piemonte, Italy. It is known for research contribution in the topics: Population & Cancer. The organization has 29607 authors who have published 77952 publications receiving 2480900 citations. The organization is also known as: Universita degli Studi di Torino & Università degli Studi di Torino.

Lactobacillus reuteri DSM 17938 in Infantile Colic: A Randomized, Double-Blind, Placebo-Controlled Trial

Abstract: OBJECTIVE: To test the efficacy of Lactobacillus reuteri on infantile colic and to evaluate its relationship to the gut microbiota. STUDY DESIGN: Fifty exclusively breastfed colicky infants, diagnosed according to modified Wessel9s criteria, were randomly assigned to receive either L reuteri DSM 17 938 (108 colony-forming units) or placebo daily for 21 days. Parental questionnaires monitored daily crying time and adverse effects. Stool samples were collected for microbiologic analysis. RESULTS: Forty-six infants (L reuteri group: 25; placebo group: 21) completed the trial. Daily crying times in minutes/day (median [interquartile range]) were 370 (120) vs 300 (150) (P = .127) on day 0 and 35.0 (85) vs 90.0 (148) (P = .022) on day 21, in the L reuteri and placebo groups, respectively. Responders (50% reduction in crying time from baseline) were significantly higher in the L reuteri group versus placebo group on days 7 (20 vs 8; P = .006), 14 (24 vs 13; P = .007), and 21 (24 vs 15; P = .036). During the study, there was a significant increase in fecal lactobacilli (P = .002) and a reduction in fecal Escherichia coli and ammonia in the L reuteri group only (P = .001). There were no differences in weight gain, stooling frequency, or incidence of constipation or regurgitation between groups, and no adverse events related to the supplementation were observed. CONCLUSION: L. reuteri DSM 17 938 at a dose of 108 colony-forming units per day in early breastfed infants improved symptoms of infantile colic and was well tolerated and safe. Gut microbiota changes induced by the probiotic could be involved in the observed clinical improvement.

Standardized definitions of molecular response in chronic myeloid leukemia

Abstract: The International Randomized Study of Interferon and STI571 (IRIS) demonstrated long-term cytogenetic responses in patients with chronic-phase chronic myeloid leukemia (CML-CP) treated with the tyrosine kinase inhibitor (TKI) imatinib. However, deep molecular responses (MRs), as measured by reductions in BCR-ABL transcript levels below the threshold of major MR, were achieved only by a small proportion of patients. With the advent of the second-generation TKIs nilotinib and dasatinib for the treatment of patients with newly diagnosed CML-CP, the proportion of patients who achieve the deepest levels of MR is likely to increase significantly. With these changes, the potential for patient eligibility in TKI cessations studies is becoming a more widely discussed topic and area for research. These developments highlight the need for robust, standardized and workable definitions of deep MRs. Specifically, it is critical that the measurement of MR is standardized in a manner to withstand both intra- and inter-laboratory variability, as well as new methodological developments. This review summarizes the relevant clinical background and proposes a framework within which standardization of MR can be taken forward.

Expression of somatostatin receptor types 1-5 in 81 cases of gastrointestinal and pancreatic endocrine tumors. A correlative immunohistochemical and reverse-transcriptase polymerase chain reaction analysis.

Abstract: Somatostatin receptors (SSTRs) have been extensively mapped in human tumors by means of autoradiography, reverse-transcriptase polymerase chain reaction (RT-PCR), in situ hybridization (ISH) and immunohistochemistry (IHC). We analyzed the SSTR type 1–5 expression by means of RT-PCR and/or IHC in a series of 81 functioning and non-functioning gastroenteropancreatic (GEP) endocrine tumors and related normal tissues. Moreover, we compared the results with clinical, pathological and hormonal features. Forty-six cases (13 intestinal and 33 pancreatic) were studied for SSTR 1–5 expression using RT-PCR, IHC with antibodies to SSTR types 2, 3, 5 and ISH for SSTR2 mRNA. The vast majority of tumors expressed SSTR types 1, 2, 3 and 5, while SSTR4 was detected in a small minority. Due to the good correlation between RT-PCR and IHC data on SSTR types 2, 3, and 5, thirty-five additional GEP endocrine tumors were studied with IHC alone. Pancreatic insulinomas had an heterogeneous SSTR expression, while 100% of somatostatinomas expressed SSTR5 and 100% gastrinomas and glucagonomas expressed SSTR2. Pre-operative biopsy material showed an overlapping immunoreactivity with that of surgical specimens, suggesting that the SSTR status can be detected in the diagnostic work-up. It is concluded that SSTRs 1–5 are heterogeneously expressed in GEP endocrine tumors and that IHC is a reliable tool to detect SSTR types 2, 3 and 5 in surgical and biopsy specimens.

PIK3CA mutations associated with gene signature of low mTORC1 signaling and better outcomes in estrogen receptor–positive breast cancer

Abstract: PIK3CA mutations are reported to be present in approximately 25% of breast cancer (BC), particularly the estrogen receptor-positive (ER+) and HER2-overexpressing (HER2+) subtypes, making them one of the most common genetic aberrations in BC. In experimental models, these mutations have been shown to activate AKT and induce oncogenic transformation, and hence these lesions have been hypothesized to render tumors highly sensitive to therapeutic PI3K/mTOR inhibition. By analyzing gene expression and protein data from nearly 1,800 human BCs, we report that a PIK3CA mutation-associated gene signature (PIK3CA-GS) derived from exon 20 (kinase domain) mutations was able to predict PIK3CA mutation status in two independent datasets, strongly suggesting a characteristic set of gene expression-induced changes. However, in ER+/HER2- BC despite pathway activation, PIK3CA mutations were associated with a phenotype of relatively low mTORC1 signaling and a good prognosis with tamoxifen monotherapy. The relationship between clinical outcome and the PIK3CA-GS was also assessed. Although the PIK3CA-GS was not associated with prognosis in ER- and HER2+ BC, it could identify better clinical outcomes in ER+/HER2- disease. In ER+ BC cell lines, PIK3CA mutations were also associated with sensitivity to tamoxifen. These findings could have important implications for the treatment of PIK3CA-mutant BCs and the development of PI3K/mTOR inhibitors.

PEGylation of proteins and liposomes: a powerful and flexible strategy to improve the drug delivery.

Abstract: PEGylation is one of the most successful strategies to improve the delivery of therapeutic molecules such as proteins, macromolecular carriers, small drugs, oligonucleotides, and other biomolecules. PEGylation increase the size and molecular weight of conjugated biomolecules and improves their pharmacokinetics and pharmacodinamics by increasing water solubility, protecting from enzymatic degradation, reducing renal clearance and limiting immunogenic and antigenic reactions. PEGylated molecules show increased half-life, decreased plasma clearance, and different biodistribution, in comparison with non-PEGylated counterparts. These features appear to be very useful for therapeutic proteins, since the high stability and very low immunogenicity of PEGylated proteins result in sustained clinical response with minimal dose and less frequent administration. PEGylation of liposomes improves not only the stability and circulation time, but also the 'passive' targeting ability on tumoral tissues, through a process known as the enhanced permeation retention effect, able to improve the therapeutic effects and reduce the toxicity of encapsulated drug. The molecular weight, shape, reactivity, specificity, and type of bond of PEG moiety are crucial in determining the effect on PEGylated molecules and, at present, researchers have the chance to select among tens of PEG derivatives and PEG conjugation technologies, in order to design the best PEGylation strategy for each particular application. The aim of the present review will be to elucidate the principles of PEGylation chemistry and to describe the already marketed PEGylated proteins and liposomes by focusing our attention to some enlightening examples of how this technology could dramatically influence the clinical application of therapeutic biomolecules.