Leek Research Articles

Abstract P2-09-21: Molecular alterations and poziotinib, a pan-HER inhibitor efficacy in human epidermal growth factor receptor 2(HER2) positive breast cancers: Combined exploratory biomarker analysis from phase II clinical trial of poziotinib for refractory HER2 positive breast cancer(BC) patients

Abstract Introduction: Poziotinib is a novel, pan-HER kinase inhibitor which showed potent anti-tumor activities through irreversible inhibition of HER family tyrosine kinases in preclinical and early clinical studies. Recent the open-label, multicenter phase II trial of poziotinib monotherapy evaluated that poziotinib is a new promising option for patients with HER2-positive metastatic BC who have failed more than two HER2 targeted therapy (NCT02418689). We evaluated genetic profiles of HER2-positive metastatic BC and investigated potential biomarkers of poziotinib for HER2-positive metastatic BC (MBC). Methods: All participants were diagnosed as HER2-positive BCs according to American Society of Clinical Oncology/College of American Pathologists HER2 guideline and provided tissue specimens that would be possible to extract DNA and RNA for next generation sequencing. We performed targeted deep sequencing with a customized 381 cancer gene panel (CancerSCAN™) and analyzed the relationship among the sequencing data, immunohistochemistry and clinical outcome. Results: From Apr 2015 to Feb 2016, 106 patients were enrolled in the trial from 7 institutes in Korea. Of 106 patients, biomarker data were available for 79 patients. TP53 was the most frequently mutated gene (70.8%) followed by PIK3CA (45.6%). HER2 single nucleotide variant (SNV) was detected in 13 BCs (16.5%) and HER3 SNV was in 9 (11.4%). The score of HER2 immunohistochemistry (IHC) was 3+ in 68 BCs and 2+ with positive in situ hybridization in 11 BCs. In copy number variant (CNV) analysis, HER2 amplification (86.1%) was most frequently observed and followed by CDK12 amplification (58.2%) and APOBEC3B deletion (30.4%). IHC score of HER2 was positively correlated to copy number (CN) of HER2 (P=0.001) but 11 breast cancer tissue did not have copy number amplification of HER2 (13.9%) (Six of HER2 IHC score 2+ and 5 of 3+). The median progression free survival (PFS) was 4.04 months (95% CI, 2.96 - 4.40) for patients who treated with poziotinib in this study. PIK3CA activating mutations were associated with short PFS compared to wild type (WT) and other SNVs (Median PFS of activating mutations vs. WT and others: 2.66 vs. 4.40 (months), P=0.009). HER2 CN amplification was positively correlated to duration of PFS (Median PFS of no amplification vs. 4 ≤ CN < 16 vs. 16 ≤ CN: 2.56 vs. 3.02 vs. 4.86 (months), P=0.032). HER2 SNVs prolonged duration of PFS without statistical significance (Median PFS of HER2 SNVs vs. WT: 4.24 vs. 3.19 (months), P=0.114), but 10 of 13 BCs with HER2 SNV (76.9%) had clinical benefit from poziotinib and 5 BCs (38.5%) had durable response more than 6 months. Conclusion: In this biomarker analysis, SNV of HER2 was frequently observed in HER2 positive MBCs and HER2 CN amplification was detected not in all. High CN amplification of HER2 derived longer PFS than those with low CN. To contrary to this, activating PIK3CA mutations shorten PFS compared to those with WT. In addition, HER2 SNVs might be a potential biomarker of poziotinib in HER2-positive MBC. Further functional study would be warranted. Citation Format: Kim J-Y, Lee E, Park K, Jung HH, Park W-Y, Lee K-H, Sohn JH, Lee KS, Jung KH, Kim J-H, Lee KH, Im S-A, Park YH. Molecular alterations and poziotinib, a pan-HER inhibitor efficacy in human epidermal growth factor receptor 2(HER2) positive breast cancers: Combined exploratory biomarker analysis from phase II clinical trial of poziotinib for refractory HER2 positive breast cancer(BC) patients [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-09-21.

Abstract GS2-05: First-line ribociclib vs placebo with goserelin and tamoxifen or a non-steroidal aromatase inhibitor in premenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer: Results from the randomized phase III MONALEESA-7 trial

Abstract Background:Endocrine therapy (ET) with ovarian function suppression is an established first-line treatment for pre- and peri-menopausal women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2–) advanced breast cancer (ABC). Addition of ribociclib (orally bioavailable, selective cyclin-dependent kinase [CDK] 4/6 inhibitor) to first-line ET prolonged progression-free survival (PFS) in a Phase III trial of postmenopausal women with HR+, HER2– ABC (MONALEESA-2). Here we report results from MONALEESA-7 (NCT02278120), the first double-blind, randomized, Phase III trial evaluating ribociclib + tamoxifen/non-steroidal aromatase inhibitor (NSAI) and goserelin specifically in pre- and peri-menopausal patients. Methods: Pre- or peri-menopausal women with HR+, HER2– ABC who had received ≤1 line of chemotherapy and no prior ET for ABC were randomized (1:1) to ribociclib (600 mg/day, 3-weeks-on/1-week-off) or placebo in combination with either tamoxifen (20 mg/day) or an NSAI (letrozole [2.5 mg/day] or anastrozole [1 mg/day]) + goserelin (3.6 mg every 28 days). The primary endpoint was locally assessed PFS. Secondary endpoints included overall response rate (ORR), clinical benefit rate (CBR), and safety. Results: 672 patients were enrolled. Baseline patient characteristics were balanced between treatment arms. The primary analysis was conducted after 318 events had occurred; median time from randomization to data cut-off date was 19.2 months. The study met its primary objective: PFS was significantly improved in the ribociclib arm (median PFS = 23.8 months; 95% CI: 19.2–not reached) vs the placebo arm (median PFS = 13.0 months; 95% CI: 11.0–16.4), with a hazard ratio of 0.553 (95% CI: 0.441–0.694; p=9.83×10–8). Subgroup analyses demonstrated consistent PFS benefits for ribociclib vs placebo. In patients with measurable disease at baseline, ORR was 51% vs 36% (ribociclib vs placebo arm; p=3.17×10–4) and CBR was 80% vs 67% (p=3.40×10–4). The most frequent all-grade adverse events (Aes; ≥25% of patients; ribociclib vs placebo arm) were neutropenia (76% vs 8%), hot flush (34% vs 34%), nausea (32% vs 20%), leukopenia (31% vs 6%), and arthralgia (30% vs 27%). Of these, neutropenia (61% vs 4%) and leukopenia (14% vs 1%) were the only Grade 3/4 events reported in ≥5% of patients (ribociclib vs placebo arm). Febrile neutropenia (ribociclib vs placebo arm) occurred in 2% vs <1% of patients. Grade 3/4 QT prolongation (ribociclib vs placebo arm) was reported in 1% vs <1% of patients. Aes leading to permanent discontinuation of ribociclib + tamoxifen/NSAI + goserelin vs placebo + tamoxifen/NSAI + goserelin occurred in 4% vs 3% of patients. Conclusions: MONALEESA-7, the first dedicated trial investigating a CDK4/6 inhibitor in pre- and peri-menopausal women with HR+, HER2– ABC, demonstrated that addition of ribociclib to first-line ET (tamoxifen/NSAI + goserelin) significantly prolonged PFS and had a manageable safety profile. The trial validates the clinical utility of ribociclib with multiple endocrine therapies, including tamoxifen, in premenopausal women with HR+, HER2– ABC. Citation Format: Tripathy D, Sohn J, Im S-A, Colleoni M, Franke F, Bardia A, Harbeck N, Hurvitz S, Chow L, Lee KS, Campos-Gomez S, Villanueva Vazquez R, Jung KH, Carlson G, Hughes G, Diaz-Padilla I, Germa C, Hirawat S, Lu Y-S. First-line ribociclib vs placebo with goserelin and tamoxifen or a non-steroidal aromatase inhibitor in premenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer: Results from the randomized phase III MONALEESA-7 trial [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr GS2-05.

Abstract GS2-07: MANTA - A randomized phase II study of fulvestrant in combination with the dual mTOR inhibitor AZD2014 or everolimus or fulvestrant alone in estrogen receptor-positive advanced or metastatic breast cancer

Abstract Background: Resistance to endocrine therapy remains a major clinical challenge with aberrant PI3K/ mTOR pathway activation being one of the main drivers. Randomised clinical trials have demonstrated a substantial benefit of adding everolimus to endocrine therapy. Vistusertib (AZD2014), a dual inhibitor of mTORC1 and mTORC2, has shown a broader range of activity in preclinical ER+ breast cancer models, showing superior activity to everolimus (EVE) both in hormone-sensitive and resistant models. The MANTA trial was desgined to evaluate the safety and efficacy of vistusertib (VIS) in combination with fulvestrant (FULV) relative to FULV alone or FULV + EVE. In addition to a continuous (cont) daily schedule of VIS, the study also explored an intermittent (int) schedule to assess the potential of short-term, maximum target inhibition. Methods: MANTA is an investigator-led, randomised, open-label phase II trial. Postmenopausal women with estrogen-receptor (ER)-positive breast cancer were eligible if they had disease recurrence while on or within 12 months of end of adjuvant treatment with an aromatase inhibitor (AI), or progression while on or within one month of end of AI treatment for locally advanced or metastatic breast cancer. Patients were randomly assigned (2:3:3:2) to receive either FULV (500 mg intramuscular injection on day 1, followed by 500 mg doses on days 15 and 29, and then every 28 days); FULV + daily VIS (50mg BD), FULV + intermittent VIS (2 days on, 5 days off; 125mg BD); or FULV + EVE (10mg OD). Treatment was given until disease progression (RECIST 1.1) or intolerable toxicity. Patients were stratified by disease measurability and response to prior endocrine therapy. The primary endpoint was investigator-assessed progression-free survival (PFS). Secondary objectives included objective response, clinical benefit rate, duration of response and clinical benefit, overall survival and safety. Results: Between 04/2014 and 10/2016, a total of 333 patients were randomised at 88 sites in 9 countries. 66 patients were assigned to receive FULV; 101 to FULV+VIS (cont), 95 to FULV+VIS (int); and 64 to FULV+EVE. Median PFS was 4.6 months (95% CI 3.4–6.9) in patients assigned to FULV; 7.5 months (95% CI 5.6–9.4) in those assigned to FULV+VIS (cont); 7.6 months (95% CI 5.5–9.6) in those assigned to FULV+VIS (int); and 12.2 months (95% CI 7.5–14.3) in those assigned to FULV+EVE. No significant difference was recorded between the patients assigned to FULV+VIS (cont) and FULV (hazard ratio 0.87, 95% CI 0.62-1.23; log-rank p=0.42); FULV+VIS (int) and FULV (HR 0.78, 95% CI 0.55-1.12; log-rank p=0.16); and FULV+VIS (cont) and FULV+VIS (int) (HR 1.11, 95% CI 0.81-1.52; log-rank p=0.52). PFS was significantly longer in patients assigned to FULV+EVE compared to FULV+VIS (cont) (HR 0.64, 95% CI 0.45-0.91; log-rank p=0.01) and FULV+EVE compared to FULV (HR 0.64, 95% CI 0.43-0.94; log-rank p=0.02). Conclusion: The trial failed to demonstrate a benefit of adding the TORC1/2 inhibitor vistusertib (AZD2014) to FULV. The combination FULV+EVE demonstrated significantly longer PFS compared to FULV+VIS or FULV. Citation Format: Schmid P, Zaiss M, Harper-Wynne C, Ferreira M, Dubey S, Chan S, Makris A, Nemsadze G, Brunt AM, Kuemmel S, Ruiz Cabrero I, Perelló A, Kendall A, Brown J, Kristeleit H, Conibear J, Saura C, Grenier J, Máhr K, Schenker M, Sohn JH, Lee KS, Sarker S-J, Coetzee C, Mousa K, Cortes Castan J. MANTA - A randomized phase II study of fulvestrant in combination with the dual mTOR inhibitor AZD2014 or everolimus or fulvestrant alone in estrogen receptor-positive advanced or metastatic breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr GS2-07.

Stale seedbed technique for weed control negatively impacts the indigenous AM fungal population

Among weed control tools available to organic farmers are a variety of stale seedbed techniques. Stale seedbed methods create a surface layer of soil depleted in viable weed seeds through repetitive cycles of seed germination followed by cultivation to uproot and kill those seedlings. Two experiments were conducted to examine the impact of two stale seedbed techniques, roto-tilling and spading (each at two frequencies), upon the native AM fungal communities in organically farmed high P soils. Weed biomass, propagule densities of the indigenous AM fungal communities, development of mycorrhizas in roots of transplanted leek (Allium porrum L.) seedlings, and impact of AM fungus inoculation upon growth and yield were measured for repetitively cultivated vs. control planting beds. Stale seedbed treatments had significant negative impact upon total weed biomass the first month after planting the leek seedlings. Control beds, cultivated only just before planting, had significantly greater AM fungus propagule density than soils roto-tilled (Pr > F = 0.0004) or spaded (Pr > F = 0.0008) at 2–4 week intervals. Early season development of mycorrhizas in transplanted seedlings was greater in the control beds than in repetitively cultivated beds, e.g. 6% vs. 1% of root length colonized (Pr > F = 0.0001) two weeks after transplanting in Exp II. Even though the stale seedbed techniques had negative impacts upon the indigenous AM fungal populations, there was no measurable impact on crop yield in the high P soils used here. Nevertheless, farmers may want to consider use of AM fungus inoculation of vegetable seedlings transplanted into stale seedbed-treated fields low in plant available P.

Yield losses in vegetable and arable crops caused by yellow nutsedge ( Cyperus esculentus ) in farmers fields in Switzerland

Cyperus esculentus has become a serious weed in Switzerland. Despite intensive awareness training unaffected farmers tend to underestimate the consequences of C. esculentus infestation, especially the potential yield losses. Hence, countermeasures are often taken hesitantly. Yield loss data from abroad is widely available. However, this data was of limited value to raise awareness in Switzerland, because its transferability to our production systems was questioned. To close this gap yield losses caused by C. esculentus were determined for different crops in farmers’ fields in Switzerland (2013-2016). Yield was assessed with and without C. esculentus infestation and its coverage was estimated. Standard herbicides had been applied in the fields. For sugar beet and potatoes average, actual yield losses of 67% and 34% were detected at C. esculentus coverages of 68% and 44%, respectively. High infestation (80-100%) in leek, onions and Brussels sprouts caused losses of 86%, 90%, 93%, accordingly. In carrots: A high infestation led to 61% yield loss. At these infestation levels yield quality was also negatively affected. In Switzerland, these figures are employed to further train farmers. The findings are presented here to make this more recent yield loss data available to colleagues facing the same problem in their countries.

Response of Leek (Allium porrum L.) to Different Irrigation Water Levels Under Rain Shelter

ABSTRACTA pot experiment was conducted to investigate the effects of different water levels on water-use efficiency, yield and growth parameters of leek (Allium porrum L.) and was carried out in the practical research field of Ondokuz Mayıs University in Turkey. Different irrigation water levels were based on the weight changes of each pot and included 5 irrigation treatments [25% (I25), 50% (I50), 75% (I75), 100% (I100) and 118% (I118) times of consumed water]. Decreases in irrigation water resulted in decreases in plant height, stem diameter, leaf and stem fresh weights, leaf and stem dry weights and leaf area, but did not significantly affect leaf number or chlorophyll content. A yield-response factor of 1.26 was obtained, implying that the leek crop was sensitive to water stress caused by deficit irrigation. Comprehensive analysis of yield, water use efficiency, and evapotranspiration, the I75 treatment can be suggested for leek production in water-scarce regions.

Opportunities and risks of biofertilization for leek production in urban areas: Influence on both fungal diversity and human bioaccessibility of inorganic pollutants

The influence of biofertilization with arbuscular mycorrhizal fungi (AMF) on trace metal and metalloids (TM) - Pb, Cd and Sb - uptake by leek (Allium porrum L.) grown in contaminated soils was investigated. The effect of biofertilization on human bioaccessibility of the TM in the plants was also examined. Leek were cultivated in one soil with geogenic TM sources and one soil with anthropogenic TM, to assess the influence of pollutant origin on soil-plant transfer. Leek were grown for six months on these contaminated soils, with and without a local AMF based biofertilizer. Fungal communities associated with leek roots were identified by high throughput sequencing (illumina Miseq®) metagenomic analysis. The TM compartmentation was studied using electron microscopy in plants tissues. In all the soils, biofertilization generated a loss of diversity favoring the AM fungal species Rhizophagus irregularis, which could explain the observed modification of metal transfer at the soil-AMF-plant interface. The human bioaccessibility of Sb increased in biofertilized treatments. Consequently, this latter result highlights a potential health risk of the use of this fertilization technique on contaminated soil since further field investigation is performed to better understand the mechanisms governing (1) the effect of AMF on TM bioaccessibility and (2) the evolution of AMF communities in contaminated soils.

Evaluation and comparison of bioactive substances in selected species of the genus Allium

Allium is a genus of some 650 species belonging to the family Liliaceae. However only a few of these are important as food plants, notably garlic (Allium sativum L.), onion (Allium cepa L.), leek (Allium porrum L.) and wild garlic (Allium ursinum L.). They contain many health beneficial substances, such as sulphur compounds, vitamins (vitamin C), mineral substances (Fe, Mg, Ca, P), polyphenols (especielly quercetin) and substances antioxidant activity and fiber. In this work we evaluated the content of bioactive substances, especially the content of total polyphenols and antioxidant activity in several species (red onion, yellow onion, white onion, garlic, leek, wild garlic) of the genus Allium. Samples of plant material were collected at full maturity stages from Zohor (Slovak Republic). Zohor is an area without negative influences and emission sources. Samples of fresh species of the genus Allium were homogenized and prepared as an extract: 25 g cut plants material (red onion, yellow onion, white onion, garlic, leek, wild garlic) extracted with 50 mL of 80% ethanol for sixteen hours. These extracts were used for analyzes. The content of total polyphenols was determined using the Folin-Ciocalteu reagent (FCR). The absorbance was measured at 765 nm of wavelength versus blank. Antioxidant activity was measured using DPPHË™ (2,2-difenyl-1-picrylhydrazyl) at 515.6 nm in the spectrophotometer. In the present experiment it was found that total polyphenols content in samples ranged from 83.59 mg.kg-1 to 758.63 mg.kg-1 and values of antioxidant activity were in the range from 7.19% to 53.55%.

Engineered Nickel Oxide Nanoparticle Causes Substantial Physicochemical Perturbation in Plants.

Concentration of engineered nickel oxide nanoparticle (NiO-NP) in nature is on the rise, owing to large scale industrial uses, which have accreted the scope of its exposure to plants, the primary producers of the ecosystem. Though an essential micronutrient for the animal system, supported by numerous studies confirming its toxicity at higher dosages, nickel oxide is graded as a human carcinogen by WHO. A few studies do depict toxicity and bioaccumulation of nickel in plants; however, interaction of NiO-NP with plants is not well-elucidated. It is known that exposure to NiO-NP can incite stress response, leading to cytotoxicity and growth retardation in some plants, but a defined work on the intricate physicochemical cellular responses and genotoxic challenges is wanting. The present study was planned to explore cytotoxicity of NiO-NP in the model plant, Allium cepa L., its internalization in the tissue and concomitant furore created in the antioxidant enzyme system of the plant. The prospect of the NiO-NP causing genotoxicity was also investigated. Detailed assessments biochemical profiles and genotoxicity potential of NiO-NP on A. cepa L. was performed and extended to four of its closest economically important relatives, Allium sativum L., Allium schoenoprasum L., Allium porrum L., and Allium fistulosum L. Growing root tips were treated with seven different concentrations of NiO-NP suspension (10–500 mg L−1), with deionised distilled water as negative control and 0.4 mM EMS solution as positive control. Study of genotoxic endpoints, like, mitotic indices (MI), chromosomal aberrations (CAs), and chromosome breaks confirmed NiO-NP induced genotoxicity in plants, even at a very low dose (10 mg L−1). That NiO-NP also perturbs biochemical homeostasis, disrupting normal physiology of the cell, was confirmed through changes in state of lipid peroxidation malonaldehyde (MDA), as well as, in oxidation marker enzymes, like catalase (CAT), super oxide dismutase (SOD), and guiacol peroxidase (POD) activities. It was evident that increase in NiO-NP concentration led to decrease in MIs in all the study materials, concomitant with a spike of stress-alleviating, antioxidant enzymes-CAT, POD, SOD, and significant increase in MDA formation. Hence, it can be confirmed that NiO-NP should be treated as an environmental hazard.

Steroidal Saponin from Allium porrum

A new steroidal glycoside (1) was isolated by fractionation of total extracted substances from Allium porrum. Its structure was determined as (25R)-5α-spirostan-3β,6β-diol-12-one 3-O-β-D-glucopyranosyl-(1→2)-[β-D-fucopyranosyl-(1→3)]-β-D-glucopyranosyl-(1→4)-β-D-galactopyranoside using chemical transformations, physical constants, and spectral data.

Determination of Fe, Mn, Cu, Zn and Cd after Heat Treatment in some vegetables and Green Bean (Phaseolus vulgaris L.) grown in the Middle Black Sea Region

Background: In this study, Fe, Mn, Cu, Zn and Cd were determined after heat treatment of spinach (Spinacia oleracea L.), leek (Allium porrum L.), green bean (Phaseolus vulgaris L.),

Carbon flow from plant to arbuscular mycorrhizal fungi is reduced under phosphorus fertilization

Arbuscular mycorrhizal fungi (AMF) are plant root symbionts highly specialized upon phosphorus (P) supply to their hosts. We investigated plants’ ability to regulate carbon (C) flow to AMF depending on the soil P supply. Leek (Allium porrum), medic (Medicago truncatula), and ryegrass (Lolium perenne) were subjected to AMF inoculation and/or P fertilization in a glasshouse experiment. The C flows were traced using 13C pulse labelling. Mycorrhizal P uptake responses were lowered by P fertilization in all tested plant species. Independently from the C flow to the roots, the C flow to AMF-signature fatty acid 16:1ω5 were reduced by P fertilization in leek and ryegrass (but not in medic). Calculated mycorrhizal C costs ranged between 0.9% and 10.5% of the plant C budget. Suppression of the C flow from the plants to AMF resulted from both reduced abundance of AMF in the roots and lowered relative C income per unit of AMF biomass in P-fertilized pots. Although inconsistencies amongst different plant species demand caution in making generalizations, these results suggest an active role of host plants in regulating the C flow to AMF.

Evaluation of degradable nonwoven covers on the growth and yield of overwintering leeks

Evaluation of degradable nonwoven covers on the growth and yield of overwintering leeks

The Influence of the Ratio of Nitrate to Ammonium Nitrogen on Nitrogen Removal in the Economical Growth of Vegetation in Hybrid Constructed Wetlands

Growing vegetables economically in the use of constructed wetland for wastewater treatment can play a role in overcoming water and food scarcity. Allium porrum L., Solanum melongena L., Ipomoea aquatica Forsk., and Capsicum annuum L. plants were selected to grow in hybrid constructed wetland (CW) under natural conditions. The impact of the ratio of nitrate to ammonium nitrogen on ammonium and nitrate nitrogen removal and on total nitrogen were studied in wastewater. Constructed wetland planted with Ipomoea aquatica Forsk. and Solanum melongena L. showed higher removal efficiency for ammonium nitrogen under higher ammonium concentration, whereas Allium porrum L.-planted CW showed higher nitrate nitrogen removal when NO3–N concentration was high in wastewater. Capsicum annuum L.-planted CW showed little efficiency for both nitrogen sources compared to other vegetables.

FIRST REPORT OF ONION YELLOW DWARF VIRUS IN GARLIC FROM NIGERIA

Garlic (Allium sativum L.) is one of the most important culinary herbs in the world. Several viruses belonging to genera Potyvirus, Carlavirus, and Allexivirus are known to infect garlic (Dijk, 1994; Walkey and Antill, 1989). This study was undertaken to investigate the status of viral infection in Nigerian garlic. Ten garlic bulbs showing mild to severe mosaic symptoms each were collected in March of 2015 from two fields in Kano and Sokoto region of Nigeria. Direct antigen coated (DAC)-ELISA was performed with antisera to Onion yellow dwarf virus (OYDV) (Bioreba, Reinach, Switzerland). All the samples were positive for OYDV. To confirm the presence of OYDV, reverse transcription (RT)-PCR was performed using primers published earlier (Majumder and Baranwal, 2014) and total RNA extracted from 100 mg of leaves with the RNeasy Plant Mini kit (Qiagen, Germany) according to the manufacturer’s instructions. Expected amplicons of ca. 320 bp for OYDV were obtained from all the samples tested, indicating infection by OYDV. Direct sequencing of the PCR products produced 276 bp long nucleotide sequences with 87% identity with sequence of an OYDV isolate from leek in Vietnam (GenBank accession No. DQ925454.1). Sequence obtained from the Nigerian isolate was deposited in GenBank under accession number KU854388. To our knowledge, this is the first report of OYDV in garlic from Nigeria.

Abstract OT1-01-12: A phase II, multicenter, randomized trial of eribulin plus gemcitabine (EG) vs. paclitaxel plus gemcitabine (PG) in patients with HER2-negative metastatic breast cancer as first-line chemotherapy

Abstract Background: Metastatic breast cancer (MBC) is an incurable disease and is needed to improve effective chemotherapy. Paclitaxel plus Gemcitabine (PG) combination chemotherapy is one of the preferred chemotherapeutic regimens for patients with MBC, and was found to be proper as a maintenance chemotherapy regimen with survival benefit and feasible toxicity profile. Eribulin mesylate is a non-taxane inhibitor of microtubule dynamics of the halichondrin class of antineoplastic drugs. A recent pooled analysis of two phase II studies with eribulin showed improved overall survival in in various patient subgroups with advanced/metastatic breast cancer who had previously received an anthracycline and a taxane. Furthermore, eribulin may have rational benefit compared with paclitaxel in terms of neurotoxicity. Therefore, Eribulin plus Gemcitabine (EG) combination chemotherapy may have less neurotoxocity comparing to PG. Trial Design: Prospective randomized phase 2, open-label, two-arm, multi-center study comparing EG chemotherapy with PG chemotherapy for patients with HER-2 negative MBC as first-line chemotherapy. Eligibility Criteria: Histologically confirmed breast cancer patients, at least 19 years of age, with no prior history of chemotherapy for metastatic, recurrent breast cancer with evaluable lesions (as per RECIST, 1.1) who have adequate hematologic, renal, and hepatic function. Patients either may or may not have a prior anthracycline containing regimen. Prior hormonal therapy as a treatment of metastatic disease is allowed. Specific Aims: The primary efficacy endpoint of the trial is Progression-Free Survival (PFS). The secondary efficacy endpoints are: Time to Treatment Failure (TTF); Overall Survival (OS); neuropathic scale (FACT for Taxane QOL assessment); toxicity; duration of response; Objective Response Rate (ORR); Clinical Benefit Rate. The exploratory endpoint of the study includes pharmacogenetic profile. Statistical Methods: The initial sample size of the present study was determined based on the data derived from a previous trial on PG maintenance chemotherapy design; 6-month PFS is 70% for PG chemotherapy. This design was hypothesized that EG chemotherapy would not be inferior to PG chemotherapy. Thus, estimated PFS for each arm is 70%. Based on this estimate, we would plan to recruit a total of 100 patients (50 per arm). Considering drop-out rate of 10%, total 112 MBC patients planned to be enrolled. Present Accrual and Target Accrual:Enrollment has been completed as of March, 2016 with a target enrollment of 112 patients. Contact information:Kyung Hae Jung MD, Ph.D. khjung@amc.seoul.kr ClinicalTrials.gov Identifier: NCT02263495. Citation Format: Park YH, Im S-A, Sohn JH, Lee KS, Chae YS, Lee KH, Kim J-H, Im Y-H, Ahn JS, Kim T-Y, Lee K-H, Kim S-B, Ahn J-H, Kim GM, Park IH, Lee SJ, Han HS, Kim SH, Jung KH. A phase II, multicenter, randomized trial of eribulin plus gemcitabine (EG) vs. paclitaxel plus gemcitabine (PG) in patients with HER2-negative metastatic breast cancer as first-line chemotherapy [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr OT1-01-12.

Abstract P5-15-04: The PROCEED trial KCSG BR11-01 phase III multicenter randomized open-label study of irinotecan plus capecitabine versus capecitabine in patients previously treated with anthracycline and taxane for HER2 negative metastatic breast cancer

Abstract Purpose We investigated whether the combination of irinotecan plus capecitabine improved progression free survival (PFS) compared with capecitabine alone in patients with HER2 negative MBC previously exposed to anthracyclines and taxanes. Patients and methods A total of 211 patients were randomly assigned to irinotecan (80mg/m2 on D1 and D8) and capecitabine (1,000mg/m2 bid on D1 to D14) or capecitabine alone (1,250mg/m2 bid on D1 to D14) every 3 weeks. The primary objective was PFS; secondary objectives included overall response rate, overall survival and safety. Results Both arms were well balanced in terms of age, hormone receptor status, visceral involvement, and number of previous treatment. There was no significant difference in PFS between the combination and capecitabine monotherapy arm (median, 6.6 vs. 5.3 months; HR=0.87; 95% CI, 0.65 to 1.16; P=0.33). In patients with triple negative breast cancer (N=87), the combination treatment significantly improved PFS (median, 4.8 vs. 2.8 months; HR=0.59 ; 95% CI, 0.37 to 0.94; P=0.03). Overall response rate was higher in the combination arm though it did not reach statistical significance (42.7% vs. 29.6%, P=0.06). Overall survival did not differ between two groups (median, 2.2 vs. 1.7 years; P=0.47). Grade 3 or 4 neutropenia occurred in 39.6% in the combination arm and 10% in the monotherapy arm. Hand-foot syndrome (≥ grade 2) was more common in the monotherapy arm (23.0% vs. 12.6%). Table 1. Patient characteristics IX(N=111)X(N=100)p-valueAge (yr, median, range)50 (29-73)49 (30-80)0.47ECOG 0.80025 (22.5%)22 (22%) 185 (76.6%)76 (76%) 21 (0.9%)2 (2%) Pre-menopause28 (25.2%)29 (29%)0.64Post-menopause83 (74.8%)71 (71%) ER/PgR 0.16positive60 (54.1%)64 (64%) negative51 (45.9%)36 (36%) Adjuvant Chemotherapy86 (77.5%)72 (72%)0.43Adjuvant Endocrine46 (41.4%)39 (39%)0.78Visceral meta 1.0yes64 (57.7%)58 (58%) no47 (42.3%)42 (42%) Previous Chemotherapy 0.40012 (10.8%)12 (12%) 160 (54.1%)46 (46%) 232 (28.8%)34 (34%) 35 (4.5%)8 (8%) 42 (1.8%)0 IX, irinotecan plus capecitabine; X, capecitabine. Conclusions Irinotecan plus capecitabine did not demonstrate superior clinical activity in heavily treated HER2 negative MBC patients. The role of adding irinotecan to capecitabine in triple negative breast cancer remains to be elucidated. Citation Format: Park IH, Im S-A, Jung KH, Sohn JH, Park YH, Park K-H, Nam B-H, Kim JH, Kim H-J, Lee S, Kim T-Y, Lee K-H, Kim S-B, Lee KS, Ro J. The PROCEED trial KCSG BR11-01 phase III multicenter randomized open-label study of irinotecan plus capecitabine versus capecitabine in patients previously treated with anthracycline and taxane for HER2 negative metastatic breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-15-04.

Abstract P2-01-15: Clinical application of multimodal fluorescent-radioactive system in advanced breast cancer patients with neoadjuvant therapy; interim analysis for 65 patients

Abstract Purpose This study aimed to evaluated the identification rate and operation time of sentinel lymph node biopsy (SLNB) by a multimodal fluorescent-radioactive system (MFS) using a mixture of indocyanine green (ICG), radioisotope (RI) compared with the RI alone in advanced breast cancer patients with neoadjuvant therapy. Methods In this phase II randomized study, we enrolled 65 patients with advanced breast cancer with neoadjuvant therapy. Then, they received SLNB with either MFS or RI. We compared the identification rate, operation time of SLNB and number of sentinel lymph nodes. We also evaluated the safety. We analyzed the data of 65 patients for interim analysis. Results The mean age of the MFS group and RI group was 51.7 and 45.9 years (p=0.024), respectively. There were no differences in histopathological characteristics, including tumor size, node positivity, and hormone receptor status between two groups. The radiologic study showed the clinically complete response in axillary lymph nodes after neoadjuvant therapy. In MFS group, sentinel lymph nodes (SLNs) were identified in 30 patients and we could not identify the SLNs in one patient. In RI group, we identified the SLNs in 33 patients and also could not identify them in one patient. (p=0.947). The average numbers of SLNs in the MFS and RI group were similar. (2.32±1.10 vs. 2.18 ± 1.57, respectively; p=0.668) The operation time of SLNB was similar in the each group (11.65 ± 6.49 vs. 9.47 ± 6.26, respectively, p= 0.174) There were no complication, including allergic reactions, skin staining or necrosis. Conclusions This study is the randomized trial that compared MFS using ICG and RI and the conventional RI method for SLNB in the advanced breast cancer with neoadjuvant therapy. The multimodal fluorescent-radioactive system is a feasible and safe method for SLNB for the breast cancer patients with neoadjuvant therapy. We will evaluate the 130 patients for final analysis. Citation Format: Lee S, Jung S-Y, Kim S-K, Lee ES, Lee MH, Park SJ, Kang H-S, Lee KS, Park IH, Sim SH, Kim Y, Kwon Y, Joo J, Kang SH. Clinical application of multimodal fluorescent-radioactive system in advanced breast cancer patients with neoadjuvant therapy; interim analysis for 65 patients [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-01-15.

Abstract P2-01-12: Development of prediction model for omission of sentinel lymph node biopsy in T1 breast cancer

Abstract INTRODUCTION Axillary sentinel lymph node (SLN) biopsy is a standard method for axillary nodal staging in the treatment of breast cancer. However, along with the trends to SLN performed only without additional axillary lymph node dissection, it's time to be considered omission of SLN for selective patients. We developed a prediction model to assess the negative probability of sentinel lymph node metastasis, specifically focus on the patients with clinical T1 breast cancer. METHODS and MATERIALS The study group consisted of 513 consecutive patients with clinical T1 breast cancer, who had undergone primary surgery between 2007 and 2012. The clinicopathologic factors and imaging modalities including breast ultrasound (US), magnetic resonance imaging (MRI), chest computed tomography (CT), and positron emission tomography (PET) were evaluated. Patients who fulfilled our inclusion criteria were randomized into experimental and validation set by 3:1 ratio. In the experimental group (n = 256), multivariate logistic regression analysis was used to analyze the association of each variable with the likelihood of SLN metastases. A prediction model was developed based on the patients in the experimental group and was validated with internal patient cohorts. RESULTS Of the 513 patients, 119 (23.1%) were found to have SLN metastases. In univariate analysis, presence of lymphovascular invasion (P < 0.001) and suspicious finding of preoperative image studies (US, PET, and MRI, P < 0.001) were independent positive predictors of SLN metastases. In multivariate analysis of experimental group, estrogen receptor status (P = 0.012), presence of lymphatic invasion (P < 0.001), and suspicious finding of preoperative image studies (US, PET, and MRI, P < 0.001) were each associated with involvement of SLN. A prediction model based on this analysis consists of 9 rows including 6 variables (age, estrogen receptor status, presence of lymphatic invasion, and results of preoperative US, PET or CT, MRI). The sum of assigned points for all six variables made corresponding value of negative probability of SLN metastasis. The accuracy of prediction model applied to the validation group, as measured by the area under the receiver operating curve was 0.789. CONCLUSIONS The prediction model developed here may be a useful tool to assess SLN involvement for clinical T1 breast cancer patients. And prospective study for additional validation of the prediction model is currently in preparation, exploring the possibility of SLN biopsy omission. Citation Format: Cho JN, Song EJ, Lee MH, Jung S-Y, Lee S, Kang H-S, Sim SH, Park IH, Lee KS, Kim YJ, Kim S-K, Kwon Y, Nam B-H, Lee ES. Development of prediction model for omission of sentinel lymph node biopsy in T1 breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-01-12.

Generation, characterization and reuse of solid wastes from a biodiesel production plant

The aim of this study was to identify and characterize industrial solid wastes generated by a biodiesel production plant in Brazil, as well as to present strategies for the management of these materials. This plant produces every year around 100,000tons of biodiesel from vegetable oils and animal fats. The methodology of the study included technical visits, interviews with the operational and environmental management staff as well as analysis of documents, reports and computerized data systems. An approach to reduce the generation of hazardous waste was investigated. It was take into account the amount of raw material that was processed, reduction of landfill disposal, and the maximization of the their recycling and reuse. The study also identified the sources of waste generation and accordingly prepared an evaluation matrix to determine the types of waste with the higher potential for minimization. The most important residue of the process was the filter material impregnated with oil and biodiesel, requiring, therefore, measures for its minimization. The use of these residues in the production of ceramic artefacts (light bricks) was considered to be very promising, since no significant effect on the physico-chemical and mechanical properties of the artefacts produced was observed. Phytotoxicity test using seeds of Lactuva sativa (lettuce), Brassica juncea (mustard), Abelmoschus esculentus (okra), Chrysanthemum leucanthemum (daisy), Dendranthema grandiflorum (chrysanthemum) and Allium porrum (leek) were carried out. The results clearly show incorporation of the waste material into bricks did not influence relative germination and relative root elongation in comparison to control tests.