563 research outputs found

    Tas-102 in metastatic colorectal cancer (MCRC): Efficacy, tolerability, and quality of life in heavily pretreated elderly patients: A real-life study

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    Background: TAS-102 is an oral monotherapy, combining trifluridine and tipiracil hydrochloride, indicated for the treatment of pretreated metastatic colorectal cancer (mCRC). The aim of this real-life study is to evaluate the efficacy and safety of TAS-102 in heavily pretreated elderly patients with mCRC whose disease has progressed with standard therapies. Methods: In this retrospective observational study, we enrolled 50 elderly patients >70 years of age (median age 78 years) with a diagnosis of mCRC who were previously treated or were not considered candidates for treatment with other available therapies. Patients aged >70 years with advanced colorectal cancer and with an ECOG performance status of grade 0 (n=18) or grade 1 (n=32) were included. Overall survival and progression-free survival were the primary endpoints, whereas objective response rate, tolerability, and quality of life were the secondary endpoints. Results: Treatment with TAS-102 appeared to be well tolerated and side effects were generally mild, achieving disease control and a benefit on quality of life. The median overall survival was 6.7 (95% CI 5.7-11.3) and the median progression-free survival was 2.1 months (95% CI 1.2-3.2), estimated using the Kaplan-Meier method. Conclusion: TAS-102 represents a manageable and effective therapeutic opportunity and appeared to be well tolerated with generally mild side effects in elderly patients with mCRC who were heavily pretreated with standard therapies

    Prognostic value of diabetes and metformin use in a real-life population of head and neck cancer patients

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    Introduction: Head and neck carcinoma (HNC) is a disease with a poor prognosis despite currently available treatments. The management of patients with this tumor is often complicated by several comorbidities. Among these, diabetes is the second most frequent and its influence on the prognosis is not known.Methods: In this work, we collected data on progression free survival (PFS) and overall survival (OS) of one hundred twenty-three patients with HNC who received biweekly cetuximab maintenance treatment after first-line chemotherapy. We then compared the survival of nondiabetic patients versus diabetics' one.Results: Surprisingly, both PFS (4 vs. 5 months, HR 2.297, p < 0.0001) and OS (7 vs. 10 months, HR 3.138, p < 0.0001) were in favor of diabetic patients, even after excluding other clinical confounding factors. In addition, we also studied survivals in patients taking metformin, a widely used oral antidiabetic drug that has demonstrated antitumor efficacy in some cancers. Indeed, diabetic patients taking metformin had better PFS and OS than those not taking it, 7 vs. 5 months (HR 0.56, p = 0.0187) and 11 vs. 8.5 months (HR 0.53, p = 0.017), respectively.Discussion: In conclusion, real-world outcomes of biweekly cetuximab maintenance remain comparable to clinical trials. The prognostic role of diabetes and metformin was confirmed to be significant in our series, but further prospective studies are needed for a definitive evaluation

    Kinetics of Formation of Butyric and Pyroglutamic Acid during the Shelf Life of Probiotic, Prebiotic and Synbiotic Yoghurt

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    Butyric acid (C4) and pyroglutamic acid (pGlu) exert significant beneficial effects on human health. In this study, the influence of probiotics (Lactobacillus acidophilus and Bifidobacteria) and/or prebiotics (1 and 3% inulin and fructo-oligosaccharides) on the content of C4 and pGlu in yoghurt during the shelf-life period was evaluated. The contents of C4 and pGlu were determined in probiotic, prebiotic and synbiotic yoghurts during 30 days of storage at 4 ◩C by solid-phase microextraction coupled with gas chromatography/mass spectrometry and HPLC analysis. Traditional yoghurt and uninoculated milk were used as control. Prebiotic yoghurt contained more C4 (2.2–2.4 mg/kg) than the uninoculated milk, and no increase was detected with respect to traditional yoghurt. However, probiotic yoghurt showed 10% more C4 than traditional yoghurt. Adding fibre to probiotics (synbiotic yoghurt) the C4 content increased by 30%. Regarding pGlu, probiotic yoghurt presented the highest content of approximately 130 mg/100 g. Fibre did not affect pGlu content. Finally, C4 and pGlu contents generally increased up to 20 days of storage and then decreased up to 30 days of storage. The results might be useful for the preparation of other functional foods rich in C4 and pGlu using lactic acid bacteria

    Novel targets for immune-checkpoint inhibition in cancer.

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    Immune-checkpoint inhibitors have revolutionized cancer therapy, yet many patients either do not derive any benefit from treatment or develop a resistance to checkpoint inhibitors. Intrinsic resistance can result from neoantigen depletion, defective antigen presentation, PD-L1 downregulation, immune-checkpoint ligand upregulation, immunosuppression, and tumor cell phenotypic changes. On the other hand, extrinsic resistance involves acquired upregulation of inhibitory immune-checkpoints, leading to T-cell exhaustion. Current data suggest that PD-1, CTLA-4, and LAG-3 upregulation limits the efficacy of single-agent immune-checkpoint inhibitors. Ongoing clinical trials are investigating novel immune-checkpoint targets to avoid or overcome resistance. This review provides an in-depth analysis of the evolving landscape of potentially targetable immune-checkpoints in cancer. We highlight their biology, emphasizing the current understanding of resistance mechanisms and focusing on promising strategies that are under investigation. We also summarize current results and ongoing clinical trials in this crucial field that could once again revolutionize outcomes for cancer patients

    Blood profile and productive performance after partial substitution of maize grain with ancient wheat lines by-products in organic laying hens' diet

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    The aim of this research was to evaluate the effects of the partial substitution of maize grain with local ancient wheats by-products in an organic laying hens farm on animal performance and blood profile, as well as on eggs quality. A total of 80 Hy-Line W-36 Single Comb White Leghorn, 18 weeks old hens were homogenously divided into two groups. The two groups (40 laying hens each, 8 replicates, 5 hens/replicate) were fed two isoprotein and isoenergetic diets: the Control group (C) was fed a standard, organic maize-soybean meal diet whereas in the Ancient Grains group (AG) part of the maize grain was replaced by a mix of ancient grains middling, consisting in 50:50 of Triticum aestivum var. spelta (spelt) and Triticum durum dicoccum L. (emmer wheat). The birds fed the maize based-diet (C) showed a higher (P < 0.01) egg weight and feed intake than the Ancient Grains (AG) group. By contrary, the feed conversion ratio was more favourable (P < 0.05) in hens fed the Ancient Grains diet. The eggs produced by the hens fed the Control diet showed higher length and width than the other group (P < 0.01). The shell thickness and strength were also higher in the Control group (P < 0.01 and P < 0.05, respectively). The experimental dietary treatment positively affected some blood parameters. The Control group showed higher levels of cholesterol and triglycerides (P < 0.05) as well as of alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) (P < 0.01). In addition, butyrate, which may have great implications for the regulation of the immune response, resulted significantly higher in the caecal content of hens from the Ancient Grains group. Overall, the Ancient Grains diet seemed to be able to guarantee the production performances with positive effects on the animal health

    Proteomic study of muscle sarcoplasmic proteins using AUT-PAGE/SDS-PAGE as two-dimensional gel electrophoresis

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    The conversion of muscle to meat in pig involves mainly proteolysis of myofibrillar proteins, which undergo notable changes since early stage of rigor mortis, even after 48 h post mortem. The tenderness of meat has been thoroughly investigated to understand the biochemical mechanisms, which influence texture and flavour development as well as the technological parameters and hence meat quality. Cytoplasmic proteolytic calcium dependent enzymes, named -and m-calpains, which act in the early stages of rigor mortis, significantly contribute to tenderization weakening myofibrils. These enzymes, however, act for fewdays because they are specifically inhibited by calpastatin and by pH lowering. However, when pH falls to about 5.0, proteolytic activity on muscle proteins is continued by longer acting lysosomal proteinase, cathepsins [3,7–9]. Post mortem proteolysis also causes relevant changes in sarcoplamic protein fraction, which represent the water soluble fraction (quantitatively about 30–35%) of meat total protein, and the involved proteins has already been identified by proteomic-based studies. Recent investigations have demonstrated that the most commonly found Lactobacillus species in dry fermented meats are able to hydrolyse myofibrillar and sarcoplasmic muscle proteins in vitro.The most abundant sarcoplasmic proteins, as mixture of basic polypeptides with a narrow spread range of molecular masses, represented an excellent model to test our analytical technique and to delineate its capabilities. In the present study, we compared 2D AUT-PAGE/SDSPAGE maps of water-soluble proteins extracted from fresh meat and from dry-cured ham, a non fermented product, from “Naples-type” salami, a microbiologically fermented product, and from “Coppa”, a typical semi-fermented product. Electrophoretically separated proteins have been identified by MALDI-ToF mass fingerprinting
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