bluuebunny/crossref_metadata_2025_split huggingface dataset:
Krill oil to improve blood lipids status in advanced cancer patient with cachexia.
Authors: Serpe Roberto , Madeddu Clelia , Panzone Filomena , Antoni Giorgia , Cau Maria Chiara , Macciò Antonio , Mantovani Giovanni , Banni Sebastiano 
Published: March 2020

e19634 Background: Cancer patients with cachexia symptoms often show a lipid profile disorder, consisting in severe hypertriglyceridemia due to increased circulating free fatty acids and variable total cholesterol levels, decreased activity of lipoprotein lipase and increased lipolysis, which is correlated with proinflammatory cytokines levels, particularly IL-6 and TNFα. Recent evidence further confirms impairment of adipose tissue metabolism in inflammatory condition like cancer cachexia. The aim of this study was to assess the effect of nutritional supplementation with Omega 3 fatty acids (EPA and DHA) in the form of Krill Oil, on main parameters of blood lipid profile and on IL-6 and TNFα blood levels. Methods: In 2011, 34 IV stage cachectic patients (M/F 20/14; age range 55-85 y) with cancer at different sites were enrolled. 21 healthy subjects were studied as controls. All patients had high blood tryglicerides, low total cholesterol levels , high levels of blood IL-6 and TNFα compared to controls. Patients received 3 capsules (3 g/day) of krill oil (Superba™ Krill Oil, Aker Biomarine, Norway), which is an oil extract from the crustacean krill (Euphausia Superba) which contains Omega-3 series unsaturated fatty acids in phospholipidic form, of which 98 % are EPA and DHA mainly in phospholipid form. Treatment duration was 2 months. Results: A significant reduction of tryglicerides blood levels (148.23 ± 88.06 vs 114 ± 55.8 mg/dl) and a significant improvement of HDL cholesterol (42.5 ± 15.6 vs 60.9 ± 12.3 mg/dl) and Total Cholesterol (135.6 ± 46.3 vs 159 ± 41.1 mg/dl) was observed after treatment. Cytokines Il-6 and TNFα blood levels did not change significantly after treatment Conclusions: Nutritional supplementation with krill oil showed a positive activity in the regulation of blood lipid profile, involving different metabolic and inflammatory pathways, probably mainly affecting hormone-sensitive lipase activity. Our data suggest that krill oil could be useful in multi-targeted combined pharmaco-nutritional approaches to treat cancer-cachexia. Additional phase III clinical studies are warranted.
Supportive care in cancer organization in France: State of the art.
Authors: Scotte Florian , Herve Christian , Bugat Roland , Farsi Fadila , Namer Moise , Tourani Jean-Marc , Tournigand Christophe , Yazbek Gabriel , Richard Sandrine , Oudard Stephane , Krakowski Ivan ,   Association Francophone pour les Soins Oncologiques de Support
Published: March 2020

e19640 Background: Second Cancer Act was defined in France in December 2009 including enhancement of supportive care in Cancer (SCC). How are supportive care organized in France? Are patients informed about supportive treatment side effects? Methods: The AFSOS (French Speaking Association for Supportive Care in Cancer) conducted this observational study to evaluate practices, organizations and informations given to patients (pts) about SCC. Among 1621 french medical doctors (MD) caring cancer pts who were sent an adhoc questionnaire, 20% (330 MD including 44% medical oncologists) answered. Results: Three different organizations were described: Single MD, transversal team and specific structure specialized in global care (specifically developed in comprehensive cancer centers-CCC). Psycho-oncology, palliative care, nutrition and pain care were the four main items considered as supportive care. During their disease, 68% of pts are receiving SCC, presented by their MD (88%) or nurse devoted to announcement of disease and SCC information (57%). Supportive care is more dispensed during palliative period (90%) than at diagnosis (44%). Patients information is rather supplied during palliative care (85%) than at diagnosis (52%) using a specific questionnaire for outpatient (20%) or specific supportive care session (17%). 71% of cancer department have a cross team to provide supportive care, with specific SCC team particularly in CCC (62%; p=0.01)). 37% have inpatient specific units. Only 40% have a specific organization in home care connection, more in CCC than in public or private centers (respectively 69%, 45%, 20%; p=0.01). 73% use specific financial valorization of CSC activity. Adverse events information is dispensed to 54% of the pts for erythropoiesis stimulating agents (ASE), 74% for biphosphonates and 94% for opioids treatments, rather by medical oncologist than other specialists (p=0.01). Conclusions: Specific organization developed especially in comprehensive cancer centers seems to facilitate SCC organization and information to pts. In the mean time, recommendations include this information, involvement in supportive care team and methods have to be enhanced. Further results compared with patient point of views are expected.
Clinical significance of mutational status in gastrointestinal stromal tumors (GIST).
Authors: Arkhiri Peter , Stilidi Ivan S. , Poddubnaya I. , Nikulin Maxim P. , Tsymzhitova Natalia , Mazurenko Natalia N. 
Published: March 2020

e20501 Background: Mutational status of GIST patients plays an important role in clinical practice. In most cases, mutations are localized in KIT exon 11. KIT exon 9 mutations are less common and are associated with poor prognosis. The study aims to analyze the prognostic role of mutational status and type of mutation in GIST patients. Methods: Analysis of the mutational status of 52 GIST patients with localized disease was conducted between January 1, 2001 and November 1, 2007. KIT/PDGFRA tyrosine kinase inhibitors were used in the treatment of GIST patients with diseases progression only. Results: 89.6% of KIT mutations were associated with spindle cell stromal tumors while 85.7% of PDGFRA - with gastric epithelioid GISTs. KIT mutations were discovered in 40 patients (76.9%), of which 34 cases (65.5%) exhibited 11 exon, 5 (9.6%) – 9 exon and 1(1.9%) case - 13 exon. PDGFRA mutations have been detected in 7 (13.5%) patients and all of them involved 18 exon. Deletions were detected in 17 cases: 10 in patients with gastric and 7 with small intestinal GISTs. Less frequent were substitutions, in 14 patients and duplications, in 3 patients. All 5 cases with KIT 9 exon mutations were duplications in small intestine stromal tumors. Duplications and substitutions in 11 exon KIT were associated with better clinical outcome (5-year survival rate of 100.0% and 75.0 ± 21.7%) when compared with deletions and duplications in 9 exon (5-year survival rate of 48.4 ± 14.1% and 25.0 ± 21.7%). Survival analyses with deletions KIT 11 exon showed no significant difference, with 5 year survival rate in patients with gastric stromal tumors of 47.6 ± 17.1%, compared with 53.3 ± 17.3% in intestinal tumors (g = 0.6496). Conclusions: The better prognosis was observed for patients with duplications and substitutions in 11 exon KIT and worse outcome—in patients with deletions in 11 and duplications in 9 exon KIT. No prognostic difference has been detected in patients with gastric and small intestinal stromal tumors with similar mutations (deletions in KIT exon 11). The poor prognosis in small intestinal stromal tumors patients is probably due to duplications in KIT exon 9.
Analysis of Hohn (HC) and porth-a-cath (PAC) central venous catheters (CVC) adverse events (AEs) and related costs in advanced soft tissue sarcomas (STS) treated with trabectedin (TR) 24-hour (24-h) infusion therapy.
Authors: Palesandro Erica , Boccone Paola , D'Ambrosio Lorenzo , Galizia Danilo , Aliberti Sandra , Debernardi Felicino , Bona Francesco , Manca Antonio , Anselmetti Giovanni Carlo , Russo Filippo , Campanella Delia , Aglietta Massimo , Grignani Giovanni 
Published: March 2020

e20512 Background: TR is registered as second line in STS. The 24-h infusion schedule showed a better activity profile but a CVC is mandatory to administer TR with related costs and possible complications. The HC (Bard Access System, USA) is a silicone, open-ended, non-tunneled CVC characterized by low cost and easy placement and removal. We performed a retrospective analysis of STS patients (pts) treated with TR through a CVC to evaluate the incidence of CVC AEs (malfunctioning, thrombosis, infection or extravasation) in pts carrying HC or PAC. Methods: Eligible criteria were: at least 1 course of TR via CVC, adequate premedication (steroid and 4000 units/die of low molecular weight heparin), absence of previous CVC alterations or any underlying coagulation disorder. All CVC were placed in our Institution under radiological control and full medical history was available for all pts included into the study. Average total costs (placement, hospital admission, device, and medications) are 255 and 560 $ for HC and PAC, respectively. Results: Between March 2008 and October 2011 42 pts, median age 58 (20-74) yrs, received TR after placement of a CVC: 14 (33%) HC and 28 (67%) PAC. At the time of TR administration, pts had received a median of 2 (range 1-4) chemotherapeutic lines. A total of 185 courses of TR (44 via HC / 141 via PAC) were administered at a median dose of 1.3 mg/m2 with a median of 3 (1-22) courses per pts. AEs occurred after a median of 2 (range 1-6) TR courses. We recorded 13 CVC-related AEs: 7 infection (2 HC / 5 PAC), 4 thrombosis (2 HC / 2 PAC), 2 malfunctioning (1 HC / 1 PAC,) no extravasation. CVC had to be removed and substituted in 10 pts (5 HC/5 PAC) with an estimated total cost of 280 and 680 $ for HC and PAC, respectively. In PAC pts, AEs determined 5 dose delays, only. Conclusions: CVC AEs should be considered in the management of pts treated with TR. HC showed a favorable safety profile and its AEs management is easier compared to implanted CVC. If disease does not progress after 2 cycles, HC can be converted in an implanted CVC. However, HC is also an adequate and cheaper device when best supportive care is the only useful therapy left.
MicroRNAs and response to anti-EGFR therapy in metastatic colorectal cancer.
Authors: Blanco-Calvo Moisés , Haz-Conde Mar , Rodríguez-Rigueiro Teresa , Figueroa Angelica , Reboredo Margarita , Medina Villaamil Vanessa , Lorenzo-Patiño Maria J , Arnal Francisco , Antón-Aparicio Luis , Alonso-Jaudenes Curbera Guillermo , Valladares-Ayerbes Manuel 
Published: March 2020

e21002 Background: The discovery of KRAS gene as response predictive factor to anti-EGFR antibodies supposed a revolution in the pharmacological management of metastatic colorectal cancer (mCRC) patients (pts), since only KRAS native (WT) pts are possible responders (R) and susceptible to be treated with this targeted therapy. However, the appearance of non-responders (NR) among KRAS WT pts during the administration of anti-EGFR therapy has stimulated the research in additional predictive markers. Here, we explore the putative role of microRNA (miRNA) deregulation as predictive tool of response to anti-EGFR therapy in mCRC pts. Methods: Tissue samples of mCRC were obtained as formalin-fixed paraffin-embedded (FFPE) specimens from the archives of our institution, after obtaining informed consent of pts. Genomic DNA was extracted using Qiaamp DNA mini kit (Qiagen). For the mutational testing of KRAS gene, we use the TheraScreen KRAS PCR kit (DxS, Qiagen). miRNA-containing total RNA was extracted using Tripure (Roche). miRNA expression was analyzed by SYBR-green-based RT-qPCR in a LightCycler 480 (Roche) device using the Human Cancer RT2 miRNA PCR array (SABiosciences, Qiagen). First data analysis was performed with the application provided by supplier (SABiosciences, Qiagen). Bioinformatic analyses were performed in miRBase 18, TargetScanHuman 6.0 and TarBase 6.0 databases. Additional statistical analyses were performed on R 2.14 (R Foundation), SPSS 19 (IBM) and Prism (GraphPad). Results: We analyze 9 primary colon cancer and 3 non-matched normal adjacent (NAT) tissues. Tumor samples corresponded to 6 KRAS WT and 3 KRAS mutated pts. Among KRAS WT pts, 3 had shown response to anti-EGFR antibodies and 3 did not. Samples were analyzed in duplicate for the expression of 88 cancer-related miRNAs. We found 22 miRNAs significantly (p<0.01) upregulated (>4-fold) when comparing KRAS WT NR versus R pts. From these 22 miRNAs, we detected only 6 when we search in databases for experimentally tested or predicted miRNA interactions with KRAS. Conclusions: We found a miRNA signature which could be utilized as response predictive tool for anti-EGFR therapy in mCRC pts. Further analysis will be necessary to establish the performance of this signature.
MYC gene copy number (GCN) and sensitivity to anti-EGFR monoclonal antibodies in metastatic colorectal cancer (mCRC).
Authors: D'Incecco Armida , Landi Lorenza , Fountzilas George , Kalogeras Konstantine T. , Geva Ravit , Kako Severine , Robb Caroline M. , Frattini Milo , Rossi Elisa , Salvini Jessica , Ludovini Vienna , Crinò Lucio , Cappuzzo Federico , Varella-Garcia Marileila 
Published: March 2020

e21018 Background: Monoclonal antibodies against Epidermal Growth Factor Receptor (EGFR) demonstrated efficacy in mCRC patients without mutations in the KRAS gene. Previous data in breast and lung cancer suggested that MYC GCN affects sensitivity to anti-EGFR agents. Methods: This retrospective study was conducted in a cohort of 303 mCRC patients treated with cetuximab/panitumumab, either alone (N=24) or in combination with chemotherapy (N=279). MYC GCN was assessed by fluorescence in situ hybridization (FISH) in primary colorectal cancer tissue samples. Results: In the study population response rate (RR) was 28%, median progression-free survival (PFS) 5.6 months and median overall survival (OS) 11.8 months. MYC was successfully evaluated in 298 cases and was amplified in 17 patients (5.7%). Individuals with MYC amplification showed a trend for a lower RR (7.7% versus 28.9%, p=0.12), shorter PFS (3.0 months versus 5.8 months, p=0.22) and shorter OS (11.3 months versus 12.6 months, p=0.15) than patients with non-amplified tumors. A Receiver Operating Characteristic (ROC) analysis was also performed in order to verify whether a better MYC GCN cut-off could discriminate between anti-EGFR sensitive and resistant cases. In this analysis, patients with mean MYC GCN ≥2.53 (N=199, 66.8%) had a significantly higher RR (32.2% versus 19.1%, p=0.02), a longer PFS (5.8 months versus 4.5 months, p=0.06) and a longer OS (12.3 months versus 11.4 months, p=0.59) than patients with mean GCN <2.53 (N=99, 33.2%). In order to assess the potential confounding effect of KRAS and BRAF status, we further analyzed the outcome of the 81 KRAS/BRAF wild-type patients according to MYC GCN. In this subset, a trend for improved RR (42% versus 20%, p=0.05), PFS (8.6 months versus 4.2 months, p=0.16) and OS (13.5 months versus 9.7 months, p=0.51) favored MYC FISH GCN ≥2.73 patients. Conclusions: MYC amplification is a rare event in mCRC, not significantly reducing sensitivity to anti-EGFR agents. A trend for better outcome was observed in presence of increased MYC GCN.
Circulating tumor cells (CTCs) and molecular subtypes (MST) in a treatment algorithm for metastatic breast cancer (MBC).
Authors: Graham Mark , Fleming Natanya , Blumenthal Susan , Boehlke Brittani , Schuur Eric 
Published: March 2020

e21022 Background: We measured CTC s and MST of MBC [ER+, HER2- (HR+); HER2+ (H2+); or Triple Negative (TN)] in all MBC pts in our practice and used these in an algorithm to treat MBC. Methods: CTC’s were measured in 156 pts whether beginning Rx with 1st MBC (97), or under way with Rx (59). Pts had CTC s measured over 61 mo. from 11/20/06 thr. 12/31/11; 66 of the pts had died as of 12/31/11. Pts were Rx’d with an algorithm using CTC’s and MST: Pts with ≥ 5 CTC s were Rx’d with chemoRx, usually doublet ChemoRx, but accounting for pt preferences. When CTC’s improved to < 5 for a sustained 3-4 mo. period, or if initially < 5m we sought less morbid therapies: hormonal if ER+, or single agent ChemoRx +/- biologics if ER- or hormone refractory. In a detailed statistical analysis of variables affecting Disease Specific Survival (DSS) in the first 140 pts thr. 6/30/11, with median f/u of 24.0 mo., highest CTC level (max CTC) observed during f/u was used for analysis: CTC Low (max <5, n=60); CTC Moderate (max 5-99; n=55); and CTC High (max ≥ 100; n=25). Results: We reported the distribution of pts and death rates for the 3 MST and the 3 max CTC groupings earlier (Graham, ASCO 2010); the conclusions are similar with 156 pts and longer f/u. Each MST has 40% of pts with 0-4 CTC’s at all time points. Each MST has a smaller group with CTC’s ≥ 100, 16% of all pts. 33% of deaths (22 of 66) occurred in the ≥ 100 CTC pts. 88% with ≥ 100 CTC’s died; these are early deaths. Only 13 of 66 (20%) died if CTC’s < 5, and 31 of 65 (48%) ifh 5-99 CTC’s. In the first 140 pt analyzed thr. 6/30/11, the median DSS from date of highest CTC is not reached for the CTC Low (max. f/u 54 mo.), vs. 35.8 mo. in the CTC Moderate and 3.3 mo. in the CTC High. DSS was signif. longer for the CTC Low and CTC Moderate vs. the CTC High (P<0.001 for both comparisons). DSS was also signif. greater in the CTC Low vs. the CTC Moderate (P = 0.04). Cox multivariate analysis showed that the Max CTC group (HR 4.8, 95% CI 3.1 - 7.6, p < 0.001), age ≥ 55 at time of max CTC (HR 4.0, 95% CI 2.7 - 7.9, p < 0.001), and MST (HR 2.1, 95% CI 1.4 – 3.1, p < 0.001) were predictive of DSS. Conclusions: a. A treatment algorithm of CTC’s and MST in MBC finds subgroups of MBC with long, intermediate and very short DSS; b. Effective treatments are short-lived in pts with CTC max ≥ 100.
Variations of T cells following metronomic and standard chemotherapy in patients with solid tumors.
Authors: Koumarianou Anna , Christodoulou Marianna , Papadopoulos Iordanis , Stergiopoulos Spyros , Peros George , Dimitriadis George , Tountas Nikolaos , Economopoulos Theofanis , Pectasides Dimitrios G. , Pappa Vassiliki , Xiros Nikolaos 
Published: March 2020

e21027 Background: Evidence suggests that the interaction of chemotherapy with effector (Teffs) and suppressor (Tregs) T-cells may influence the survival of patients. We investigated the impact of metronomic (p.o.) and standard intravenous (i.v.) chemotherapy on Tregs and Teffs. Methods: Blood samples were collected from 37 cancer patients, before (pre) and after (post) the first cycle of i.v. (n=18) or p.o. (n=19) chemotherapy. CD4+CD25- Teffs and CD4+CD25+ Tregs were freshly isolated with magnetic-bead sorting (Miltenyi Biotec). Teffs:Tregs co-cultures were developed in the presence of CD2, CD3 and CD28 antibodies for the study of the Tregs over Teffs suppressive capacity. The cell proliferation was evaluated utilizing a colorimetric ELISA (O.D. at 450 nm) (Roche Applied Science). Statistical analyses using Mann-Whitney and Tukey’s (one-way ANOVA) tests were performed in order to determine if changes in the numerical and/or functional T-cell characteristics occurred in association with a particular chemotherapy approach. Results: Decreased numbers of total T-cells were observed in all patients regardless chemotherapy type. The post-chemotherapy group displayed higher ratio of Tregs to Teffs cells as well as higher Tregs over Teffs suppression (expressed as the % difference in Teff proliferation rate between single Teffs cultures and Teffs:Tregs co-cultures) compared to the pre-chemotherapy group (0.17±0.02 vs 0.09±0.07, p=0.002 and 30.65%±12.12 vs 10.65%±16.80, respectively). Subgroup analyses revealed that these parameters were significantly higher in patients treated with p.o. chemotherapy compared to those treated with i.v. chemotherapy (0.21±0.04 vs 0.12±0.03, p=0.01 and 44.43%±7.34 vs 16.87%±22.99, respectively). Patients receiving drugs targeting the mitotic spindle, such as docetaxel or vinorelbine, exhibited a stronger Tregs suppression (44.32%±6.78) as compared to those treated with DNA sequence-interfering drugs, such as epirubicin or cisplatin (10.30%±38.85). Conclusions: Chemotherapy influences the immune response in favor of Tregs and against Teffs in a drug-specific manner. Compared to i.v., p.o. chemotherapy correlates with greater repression of Teffs function.
Effect of targeting of syndecan-1 by microRNA miR-10b on breast cancer cell motility and invasiveness via a rho-GTPase- and E-cadherin-dependent mechanism.
Authors: Kiesel Ludwig , Ibrahim Sherif Abdelaziz , Yip George W , Gotte Martin 
Published: March 2020

e21041 Background: microRNAs are small endogenous non-coding RNAs, which posttranscriptionally regulate gene expression. In breast cancer, overexpression of the transmembrane heparan sulfate proteoglycan syndecan-1, a predicted target of the oncomiR miR-10b, correlates with poor clinical outcome. Here, we investigatet the potential functional relationship of miR-10b and syndecan-1 in an in vitro study. Methods: MDA-MB-231 and MCF-7 breast cancer cells were transiently transfected with pre-miR-10b, syndecan-1 siRNA or control reagents, respectively. Altered cell behaviour was monitored by proliferation, migration and invasion chamber assays, and time-lapse video microscopy. Results: miR-10b overexpression induced posttranscriptional downregulation of syndecan-1, as demonstrated by qPCR, flow cytometry, and 3’UTR luciferase assays, resulting in increased cancer cell migration and matrigel invasiveness. Syndecan-1 silencing generated a copy of this phenotype. Adhesion to fibronectin and laminin and basal cell proliferation were increased. Syndecan-1 co-immunoprecipitated with focal adhesion kinase, which showed increased activation upon syndecan-1 depletion. Affymetrix screening and confirmatory qPCR and Western blotting analysis of syndecan-1 deficient cells revealed upregulation of ATF-2, COX- 2, cadherin-11, vinculin, ACTG2, MYL9, transgelin-1, RhoA/C, MMP2 and heparanase, and downregulation of AML1/RUNX1, E-cadherin, CLDN1, p21WAF/CIP, Cdk6, TLR-4, PAI1/2, Collagen1alpha1, JHDM1D, Mpp4, MMP9, matrilin-2 and ANXA3/A10. Video microscopy demonstrated massively increased Rho kinase-dependent motility of syndecan-1-depleted cells, which displayed increased filopodia formation. Conclusions: We conclude that syndecan-1 is a novel target of the oncomiR miR-10b. Rho-GTPase dependent modulation of cytoskeletal function and downregulation of E-cadherin expression are identified as relevant effectors of the miR-10b-syndecan-1 axis, which emerges as a promising target for the development of new therapeutic approaches for breast cancer.