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Recent reports identify the ratio between absolute neutrophil count (ANC) and absolute lymphocyte count (ALC), called neutrophil to lymphocyte ratio (NLR), as a predictor of progression-free survival (PFS) and overall survival (OS) in various malignancies. We retrospectively examined the NLR in a cohort of 309 newly diagnosed multiple myeloma (MM) patients treated upfront with novel agents. NLR was calculated using data obtained from the complete blood count (CBC) at diagnosis and subsequently correlated with PFS and OS. The median NLR was 1.9 (range 0.4-15.9). Higher NLR was independent of international staging system (ISS) stage, plasma cell infiltration or cytogenetics. The 5-year PFS and OS estimates were, respectively, 18.2 and 36.4 % for patients with NLR ≥ 2 versus 25.5 and 66.6 % in patients with NLR < 2. Among younger patients (age <65 years, N = 179), NLR ≥ 2 had a negative prognostic impact on both PFS and OS, in all ISS stages. By combining ISS stage and NLR in a model limited to young patients, we found that 19 % of the patients were classified as very low risk, 70 % standard risk and 11 % very high risk. The 5-year estimates were 39.3, 19.4 and 10.9 % for PFS and 95.8, 50.9 and 23.6 % for OS for very low, standard-risk and very high-risk groups. We found NLR to be a predictor of PFS and OS in MM patients treated upfront with novel agents. NLR can be combined with ISS staging system to identify patients with dismal outcome. However, larger cohorts and prospective studies are needed to use NLR as additional parameter to personalise MM therapy in the era of novel agents. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) from the gene cluster miR-143-145 are diminished in cells of colorectal tumor origin when compared with normal colon epithelia. Until now, no report has addressed the coordinate action of these miRNAs in colorectal cancer (CRC). In this study, we performed a comprehensive molecular and functional analysis of the miRNA cluster regulatory network. First, we evaluated proliferation, migration, anchorage-independent growth and chemoresistance in the colon tumor cell lines after miR-143 and miR-145 restoration. Then, we assessed the contribution of single genes targeted by miR-143 and miR-145 by reinforcing their expression and checking functional recovery. Restoring miR-143 and miR-145 in colon cancer cells decreases proliferation, migration and chemoresistance. We identified cluster of differentiation 44 (CD44), Kruppel-like factor 5 (KLF5), Kirsten rat sarcoma 2 viral oncogene homolog (KRAS) and v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) as proteins targeted by miR-143 and miR-145. Their re-expression can partially revert a decrease in transformation properties caused by the overexpression of miR-143 and miR-145. In addition, we determined a set of mRNAs that are diminished after reinforcing miR-143 and miR-145 expression. The whole transcriptome analysis ascertained that downregulated transcripts are enriched in predicted target genes in a statistically significant manner. A number of additional genes, whose expression decreases as a direct or indirect consequence of miR-143 and miR-145, reveals a complex regulatory network that affects cell signaling pathways involved in transformation. In conclusion, we identified a coordinated program of gene repression by miR-143 and miR-145, in CRC, where either of the two miRNAs share a target transcript, or where the target transcripts share a common signaling pathway. Major mediators of the oncosuppression by miR-143 and miR-145 are genes belonging to the growth factor receptor-mitogen-activated protein kinase network and to the p53 signaling pathway. [ABSTRACT FROM AUTHOR]

Specimens of flounder Paralichthys orbignyanus (Jenyns, 1842) were collected in Bahía Blanca estuary between February 1997 and January 1998, and their feeding habits were examined in relation to season and size class. The stomach contents of 823 specimens, ranging from 70 to 875 mm total length, were analysed. Their diet included organisms from 17 taxa. The highest vacuity index values were found during autumn and winter. The stomach fullness index indicated that flounders increased their feeding activity between October and March, reaching a highest point in February and decreasing after February. Fish were the primary prey item in frequency, number and weight, followed by crustaceans, such as shrimps and crabs. A seasonal and size class variation was detected in the diet. During summer all-size flounders consumed mainly fish. In autumn, for all-size classes the main food were fish and crustaceans even though fish were dominant in terms of biomass. In spring, crustaceans (mysids Arthromysis magellanica (Cunningham), shrimps Artemesia longinaris Bate, and prawns Pleoticus muelleri (Bate)) were the dominant prey in terms of number and biomass for flounders ≤ 450 mm TL. Size classes larger than 451 mm TL fed on crustaceans and fish though the most important prey item in terms of biomass was fish. In Bahía Blanca estuary, P. orbignyanus evidenced mainly an ichthyophagou – carcinophagous diet. The results collected from the present study lead to conclude that P. orbignyanus shows, in this region, a clear preference for fish. [ABSTRACT FROM AUTHOR]

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Copyright of Il Nuovo Cimento: A is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The kinetics of the in vitro cytotoxicity of DAB486IL-2, a genetically engineered fusion protein containing a portion of diphtheria toxin and human interleukin-2, were examined in the C91/PL cell line, which constitutively expresses IL-2 receptors. Maximal inhibition of protein synthesis was observed by 4-6 h after DAB486IL-2 addition at a concentration of 300 ng/ml. The tissue distribution, urinary excretion, and plasma pharmacokinetics of DAB486IL-2 in the rat and its plasma pharmacokinetics in the monkey were also examined. In rats the primary site of distribution of [35S]-DAB486IL-2 outside the vasculature appears to be the liver, followed by the kidney, spleen, and lung. Persistence of radioactive material in the liver and urinary excretion of metabolic degradation products suggest that labeled protein is metabolized by hepatic tissue. Following i.v. bolus administration of DAB486IL-2, the initial serum half-life for both the rat and the monkey was approximately 5 min. The overall clearance rate of drug for the two species differed, with DAB486IL-2 being cleared from circulation 2-3 times more rapidly in the monkey. Presence of high levels of neutralizing antibodies to diphtheria toxin in the rat significantly influenced the clearance of bioactive DAB486IL-2. However, the question as to whether the presence of in vitro biological activity for the molecule is masked by the presence of antibodies cannot be clearly answered. [ABSTRACT FROM AUTHOR]