bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biomimetic Synthesis of Silver Nanoparticles for Preparing Preservative Solutions for Mandarins (Citrus DeliciosaTenore)
Authors: Bao Vo-Van Quoc , Vuong Le Dai , Luan Le Van 
Published: February 2018

Mandarin (Citrus deliciosa Tenore) is one of the most important fruit crops grown in the Hue province, Vietnam, and has immense economic, health and cultural significance. However, mandarins are highly perishable and more susceptible to diseases compared to other citrus fruits. In the present study, biomimetic synthesis of silver nanoparticles (AgNPs) for preparing preservative solutions for mandarins was investigated. Spherical and nanometer-sized AgNPs that were prepared with the help of ultrasound wave induced a reaction between silver nitrate solution (AgNO30.02[Formula: see text]M) and the leaf extract of Centella asiatica. Spherical AgNPs were formed easily in the extract at an ambient temperature and their average size ranged from 3[Formula: see text]nm to 30[Formula: see text]nm. These AgNPs exhibited potent antifungal activity against Macrophoma theicola B1 fungi, which were isolated from mandarin peels collected from agricultural lands of rural villages of Thua Thien-Hue province in Vietnam. Thus, we are successful in preparing an AgNPs-containing preservative solution as a mandarin fruit-coating material to inhibit the growth of M. theicola B1 fungi. The coating of mandarin fruits with this preservative solution prolonged the storage life of the fruits from 9 to 35 days. On the 35th day, the preserved fruits maintained their natural color and ripening, whereas the control sample decayed with white fungus covering its skin after 9 days of storage. Thus, coating mandarins with this solution can be proposed as an additional treatment for increasing their postharvest quality. Additionally, it can be a solution for protection against fungal infection and physiological damage and controlling the decay of mandarins, thereby prolonging their shelf life.
Cross-talk Signaling between HER3 and HPV16 E6 and E7 Mediates Resistance to PI3K Inhibitors in Head and Neck Cancer
Authors: Brand Toni M. , Hartmann Stefan , Bhola Neil E. , Li Hua , Zeng Yan , O'Keefe Rachel A. , Ranall Max V. , Bandyopadhyay Sourav , Soucheray Margaret , Krogan Nevan J. , Kemp Carolyn , Duvvuri Umamaheswar , LaVallee Theresa , Johnson Daniel E. , Ozbun Michelle A. , Bauman Julie E. , Grandis Jennifer R. 
Published: February 2018

AbstractHuman papillomavirus (HPV) type 16 is implicated in approximately 75% of head and neck squamous cell carcinomas (HNSCC) that arise in the oropharynx, where viral expression of the E6 and E7 oncoproteins promote cellular transformation, tumor growth, and maintenance. An important oncogenic signaling pathway activated by E6 and E7 is the PI3K pathway, a key driver of carcinogenesis. The PI3K pathway is also activated by mutation or amplification of PIK3CA in over half of HPV(+) HNSCC. In this study, we investigated the efficacy of PI3K-targeted therapies in HPV(+) HNSCC preclinical models and report that HPV(+) cell line- and patient-derived xenografts are resistant to PI3K inhibitors due to feedback signaling emanating from E6 and E7. Receptor tyrosine kinase profiling indicated that PI3K inhibition led to elevated expression of the HER3 receptor, which in turn increased the abundance of E6 and E7 to promote PI3K inhibitor resistance. Targeting HER3 with siRNA or the mAb CDX-3379 reduced E6 and E7 abundance and enhanced the efficacy of PI3K-targeted therapies. Together, these findings suggest that cross-talk between HER3 and HPV oncoproteins promotes resistance to PI3K inhibitors and that cotargeting HER3 and PI3K may be an effective therapeutic strategy in HPV(+) tumors.Significance: These findings suggest a new therapeutic combination that may improve outcomes in HPV(+) head and neck cancer patients. Cancer Res; 78(9); 2383–95. ©2018 AACR.
The FACT inhibitor CBL0137 Synergizes with Cisplatin in Small-Cell Lung Cancer by Increasing NOTCH1 Expression and Targeting Tumor-Initiating Cells
Authors: De Sarmishtha , Lindner Daniel J. , Coleman Claire J. , Wildey Gary , Dowlati Afshin , Stark George R. 
Published: February 2018

Abstract
Traditional treatments of small-cell lung cancer (SCLC) with cisplatin, a standard-of-care therapy, spare the tumor-initiating cells (TIC) that mediate drug resistance. Here we report a novel therapeutic strategy that preferentially targets TICs in SCLC, in which cisplatin is combined with CBL0137, an inhibitor of the histone chaperone facilitates chromatin transcription (FACT), which is highly expressed in TICs. Combination of cisplatin and CBL0137 killed patient-derived and murine SCLC cell lines synergistically. In response to CBL0137 alone, TICs were more sensitive than non-TICs, in part, because CBL0137 increased expression of the tumor suppressor NOTCH1 by abrogating the binding of negative regulator SP3 to the NOTCH1 promoter, and in part because treatment decreased the high expression of stem cell transcription factors. The combination of cisplatin and CBL0137 greatly reduced the growth of a patient-derived xenograft in mice and also the growth of a syngeneic mouse SCLC tumor. Thus, CBL0137 can be a highly effective drug against SCLC, especially in combination with cisplatin.
Significance: These findings reveal a novel therapeutic regimen for SCLC, combining cisplatin with an inhibitor that preferentially targets tumor-initiating cells. Cancer Res; 78(9); 2396–406. ©2018 AACR.
RSK Regulates PFK-2 Activity to Promote Metabolic Rewiring in Melanoma
Authors: Houles Thibault , Gravel Simon-Pierre , Lavoie Geneviève , Shin Sejeong , Savall Mathilde , Méant Antoine , Grondin Benoit , Gaboury Louis , Yoon Sang-Oh , St-Pierre Julie , Roux Philippe P. 
Published: February 2018

Abstract
Metabolic reprogramming is a hallmark of cancer that includes increased glucose uptake and accelerated aerobic glycolysis. This phenotype is required to fulfill anabolic demands associated with aberrant cell proliferation and is often mediated by oncogenic drivers such as activated BRAF. In this study, we show that the MAPK-activated p90 ribosomal S6 kinase (RSK) is necessary to maintain glycolytic metabolism in BRAF-mutated melanoma cells. RSK directly phosphorylated the regulatory domain of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 2 (PFKFB2), an enzyme that catalyzes the synthesis of fructose-2,6-bisphosphate during glycolysis. Inhibition of RSK reduced PFKFB2 activity and glycolytic flux in melanoma cells, suggesting an important role for RSK in BRAF-mediated metabolic rewiring. Consistent with this, expression of a phosphorylation-deficient mutant of PFKFB2 decreased aerobic glycolysis and reduced the growth of melanoma in mice. Together, these results indicate that RSK-mediated phosphorylation of PFKFB2 plays a key role in the metabolism and growth of BRAF-mutated melanomas.
Significance: RSK promotes glycolytic metabolism and the growth of BRAF-mutated melanoma by driving phosphorylation of an important glycolytic enzyme. Cancer Res; 78(9); 2191–204. ©2018 AACR.
The Balance Players of the Adaptive Immune System
Authors: Andersen Mads Hald 
Published: February 2018

Abstract
Equilibrium between immune activation and suppression may be necessary to maintain immune homeostasis, because proinflammatory effector T cells (defined as antiregulatory T cells) counteract the functions of regulatory immune cells. These self-reactive T cells recognize human leukocyte antigen (HLA)–restricted epitopes derived from proteins expressed by regulatory immune cells such as IDO, PD-L1, PD-L2, or arginase. The activation of such proinflammatory effector T cells offers a novel way to directly target the tumor microenvironment, potentially giving them considerable clinical value, especially in patients with cancer. Vaccination against genetically stable cells with regular HLA expression is an attractive way to directly target immunosuppressive cells in addition to attracting proinflammatory cells into the tumor microenvironment. Importantly, vaccination toward IDO or PD-L1 to potentiate such T cells have proven safe, with minimal toxicity in the clinical phase I trials conducted thus far.Cancer Res; 78(6); 1379–82. ©2018 AACR.
T-Cell Exhaustion Signatures Vary with Tumor Type and Are Severe in Glioblastoma
Authors: Woroniecka Karolina , Chongsathidkiet Pakawat , Rhodin Kristen , Kemeny Hanna , Dechant Cosette , Farber S. Harrison , Elsamadicy Aladine A. , Cui Xiuyu , Koyama Shohei , Jackson Christina , Hansen Landon J. , Johanns Tanner M. , Sanchez-Perez Luis , Chandramohan Vidyalakshmi , Yu Yen-Rei Andrea , Bigner Darell D. , Giles Amber , Healy Patrick , Dranoff Glenn , Weinhold Kent J. , Dunn Gavin P. , Fecci Peter E. 
Published: February 2018

AbstractPurpose: T-cell dysfunction is a hallmark of glioblastoma (GBM). Although anergy and tolerance have been well characterized, T-cell exhaustion remains relatively unexplored. Exhaustion, characterized in part by the upregulation of multiple immune checkpoints, is a known contributor to failures amid immune checkpoint blockade, a strategy that has lacked success thus far in GBM. This study is among the first to examine, and credential as bona fide, exhaustion among T cells infiltrating human and murine GBM.Experimental Design: Tumor-infiltrating and peripheral blood lymphocytes (TILs and PBLs) were isolated from patients with GBM. Levels of exhaustion-associated inhibitory receptors and poststimulation levels of the cytokines IFNγ, TNFα, and IL2 were assessed by flow cytometry. T-cell receptor Vβ chain expansion was also assessed in TILs and PBLs. Similar analysis was extended to TILs isolated from intracranial and subcutaneous immunocompetent murine models of glioma, breast, lung, and melanoma cancers.Results: Our data reveal that GBM elicits a particularly severe T-cell exhaustion signature among infiltrating T cells characterized by: (1) prominent upregulation of multiple immune checkpoints; (2) stereotyped T-cell transcriptional programs matching classical virus-induced exhaustion; and (3) notable T-cell hyporesponsiveness in tumor-specific T cells. Exhaustion signatures differ predictably with tumor identity, but remain stable across manipulated tumor locations.Conclusions: Distinct cancers possess similarly distinct mechanisms for exhausting T cells. The poor TIL function and severe exhaustion observed in GBM highlight the need to better understand this tumor-imposed mode of T-cell dysfunction in order to formulate effective immunotherapeutic strategies targeting GBM. Clin Cancer Res; 24(17); 4175–86. ©2018 AACR.See related commentary by Jackson and Lim, p. 4059
Mechanistic Exploration of Cancer Stem Cell Marker Voltage-Dependent Calcium Channel α2δ1 Subunit-mediated Chemotherapy Resistance in Small-Cell Lung Cancer
Authors: Yu Jiangyong , Wang Shuhang , Zhao Wei , Duan Jianchun , Wang Zhijie , Chen Hanxiao , Tian Yanhua , Wang Di , Zhao Jun , An Tongtong , Bai Hua , Wu Meina , Wang Jie 
Published: February 2018

Abstract
Purpose: Chemoresistance in small-cell lung cancer (SCLC) is reportedly attributed to the existence of resistant cancer stem cells (CSC). Studies involving CSC-specific markers and related mechanisms in SCLC remain limited. This study explored the role of the voltage-dependent calcium channel α2δ1 subunit as a CSC marker in chemoresistance of SCLC, and explored the potential mechanisms of α2δ1-mediated chemoresistance and strategies of overcoming the resistance.
Experimental Design: α2δ1-positive cells were identified and isolated from SCLC cell lines and patient-derived xenograft (PDX) models, and CSC-like properties were subsequently verified. Transcriptome sequencing and Western blotting were carried out to identify pathways involved in α2δ1-mediated chemoresistance in SCLC. In addition, possible interventions to overcome α2δ1-mediated chemoresistance were examined.
Results: Different proportions of α2δ1+ cells were identified in SCLC cell lines and PDX models. α2δ1+ cells exhibited CSC-like properties (self-renewal, tumorigenic, differentiation potential, and high expression of genes related to CSCs and drug resistance). Chemotherapy induced the enrichment of α2δ1+ cells instead of CD133+ cells in PDXs, and an increased proportion of α2δ1+ cells corresponded to increased chemoresistance. Activation and overexpression of ERK in the α2δ1-positive H1048 cell line was identified at the protein level. mAb 1B50-1 was observed to improve the efficacy of chemotherapy and delay relapse as maintenance therapy in PDX models.
Conclusions: SCLC cells expressing α2δ1 demonstrated CSC-like properties, and may contribute to chemoresistance. ERK may play a key role in α2δ1-mediated chemoresistance. mAb 1B50-1 may serve as a potential anti-SCLC drug. Clin Cancer Res; 24(9); 2148–58. ©2018 AACR.
Human Papillomavirus DNA Methylation as a Biomarker for Cervical Precancer: Consistency across 12 Genotypes and Potential Impact on Management of HPV-Positive Women
Authors: Clarke Megan A. , Gradissimo Ana , Schiffman Mark , Lam Jessica , Sollecito Christopher C. , Fetterman Barbara , Lorey Thomas , Poitras Nancy , Raine-Bennett Tina R. , Castle Philip E. , Wentzensen Nicolas , Burk Robert D. 
Published: February 2018

Abstract
Purpose: Human papillomavirus (HPV) DNA methylation testing is a promising triage option for women testing HPV positive during cervical cancer screening. However, the extent to which methylation indicates precancer for all 12 carcinogenic HPV types has not been evaluated.
Experimental Design: In this nested case–control study, we tested up to 30 cases of precancer [cervical intraepithelial neoplasia grade 3 (CIN3)/adenocarcinoma in situ (AIS)] and 30 normal controls for each carcinogenic type (single infections with 16/18/31/33/35/39/45/51/52/56/58/59). Next-generation bisulfite sequencing was performed on CpG sites within the L1 and L2 genes. We calculated differences in methylation, ORs, and AUC. Using a fixed sensitivity of 80%, we evaluated the specificity and the risk of CIN3/AIS for best performing CpG sites, and compared the performance of an explorative multi-type methylation assay with current triage strategies.
Results: Methylation was positively associated with CIN3/AIS across all 12 types. AUCs for the top sites ranged from 0.71 (HPV51 and HPV56) to 0.86 (HPV18). A combined 12-type methylation assay had the highest Youden index (0.46), compared with cytology (0.31) and a 5-type methylation assay, including only previously described types (0.26). The 12-type methylation assay had higher sensitivity (80% vs. 76.6%) and lower test positivity compared with cytology (38.5% vs. 48.7%). The risk of CIN3/AIS was highest for methylation positives and lowest for cytology or HPV16/18 positives.
Conclusions: HPV DNA methylation is a general phenomenon marking the transition from HPV infection to precancer for all 12 carcinogenic types. Development of a combined multitype methylation assay may serve as a triage test for HPV-positive women. Clin Cancer Res; 24(9); 2194–202. ©2018 AACR.
Harnessing the Power of Patient-Reported Outcomes in Oncology
Authors: Nipp Ryan D. , Temel Jennifer S. 
Published: February 2018

Abstract
Patient-reported outcomes (PRO) represent an increasingly important mechanism for incorporating patients' experiences and perspectives into their care to enhance cancer care delivery and outcomes. In this article, we discuss the importance of integrating PROs into both the clinical and research settings in oncology and highlight potential challenges. Clin Cancer Res; 24(8); 1777–9. ©2018 AACR.
See related article by Kim et al., p. 1780
Impact of the Anticancer Drug NT157 on Tyrosine Kinase Signaling Networks
Authors: Su Shih-Ping , Flashner-Abramson Efrat , Klein Shoshana , Gal Mor , Lee Rachel S. , Wu Jianmin , Levitzki Alexander , Daly Roger J. 
Published: February 2018

AbstractThe small-molecule drug NT157 has demonstrated promising efficacy in preclinical models of a number of different cancer types, reflecting activity against both cancer cells and the tumor microenvironment. Two known mechanisms of action are degradation of insulin receptor substrates (IRS)-1/2 and reduced Stat3 activation, although it is possible that others exist. To interrogate the effects of this drug on cell signaling pathways in an unbiased manner, we have undertaken mass spectrometry–based global tyrosine phosphorylation profiling of NT157-treated A375 melanoma cells. Bioinformatic analysis of the resulting dataset resolved 5 different clusters of tyrosine-phosphorylated peptides that differed in the directionality and timing of response to drug treatment over time. The receptor tyrosine kinase AXL exhibited a rapid decrease in phosphorylation in response to drug treatment, followed by proteasome-dependent degradation, identifying an additional potential target for NT157 action. However, NT157 treatment also resulted in increased activation of p38 MAPK α and γ, as well as the JNKs and specific Src family kinases. Importantly, cotreatment with the p38 MAPK inhibitor SB203580 attenuated the antiproliferative effect of NT157, while synergistic inhibition of cell proliferation was observed when NT157 was combined with a Src inhibitor. These findings provide novel insights into NT157 action on cancer cells and highlight how globally profiling the impact of a specific drug on cellular signaling networks can identify effective combination treatments. Mol Cancer Ther; 17(5); 931–42. ©2018 AACR.
Need of Emergency Surgery in Elderly Patients with Upper Gastrointestinal Bleeding: Survival Analysis during 2009–2015
Authors: Miilunpohja Sami , Kärkkäinen Jussi , Hartikainen Juha , Jyrkkä Johanna , Rantanen Tuomo , Paajanen Hannu 
Published: February 2018

<b><i>Background/Aims:</i></b> The role of emergency surgery is decreasing in the treatment of patients with upper gastrointestinal bleeding (UGIB). We investigated the need of urgent surgery and outcome of elderly UGIB patients who often have cardiovascular comorbidities with antithrombotic medication. <b><i>Methods:</i></b> All consecutive adult patients who received emergency treatment for suspected gastrointestinal bleeding between January 2009 and December 2011 were registered in an electronic database (<i>n</i> = 1,643). A total of 569 patients with a first-time UGIB were identified, of whom 282 were ≥70 years old. Age-specific incidence rates, risk factors for bleeding and need of endoscopic or emergency surgery were studied. Long-term mortality was compared to age-adjusted control subjects (<i>n</i> = 569) without bleeding. <b><i>Results:</i></b> The age-specific incidence of UGIB increased from 156 to 401 cases per 100,000 inhabitants from age 60–69 to 80–89 years, respectively. Cardiovascular comorbidities and antithrombotic therapies (acetosalicylic acid 51 vs. 27%; warfarins 25 vs. 11%) related to UGIB were more common in patients over than under 70 years of age (<i>p</i> &#x3c; 0.0001). Early endoscopic therapy was successful in over 95% of patients, whereas emergency surgery was needed only in 6 (2%) patients ≥70 years old. Hospital mortality (7.8%) was acceptable in these patients, but the 5-year mortality (40%) was significantly higher than in controls (20%, <i>p</i> &#x3c; 0.001). <b><i>Conclusion:</i></b> Today, emergency surgery is seldom needed in the patients with UGIB. In comparison to the age-matched control population, long-term survival was significantly lower after UGIB in the elderly.
Is Enhanced One-Stage Hepatectomy a Safe and Feasible Alternative to the Two-Stage Hepatectomy in the Setting of Multiple Bilobar Colorectal Liver Metastases? A Comparative Analysis between Two Pioneering Centers
Authors: Torzilli Guido , Viganò Luca , Cimino Matteo , Imai Katsunori , Vibert Eric , Donadon Matteo , Mansour Doaa , Castaing Denis , Adam Ren 
Published: February 2018

<b><i>Background:</i></b> Two-stage hepatectomy (TSH) is the present standard for multiple bilobar colorectal metastases (CLM). As alternative, ultrasound-guided one-stage hepatectomy (E-OSH) has been proposed even for deep-located nodules to compare TSH and E-OSH. <b><i>Methods:</i></b> All consecutive TSH at the Paul Brousse Hospital and E-OSH at the Humanitas Research Hospital were considered. The inclusion criteria were ≥6 CLM, ≥3 CLM in the left liver, and ≥1 lesion with vascular contact. A total of 74 TSH and 35 E-OSH were compared. <b><i>Results:</i></b> The 2 groups had similar characteristics. Drop-out rate of TSH was 40.5%. In comparison with the cumulated hepatectomies of TSH, E-OSH had lower blood loss (500 vs. 1,100 mL, <i>p</i> = 0.009), overall morbidity (37.1 vs. 70.5%, <i>p</i> = 0.003), severe morbidity (14.3 vs. 36.4%, <i>p</i> = 0.04), and liver-specific morbidity (22.9 vs. 40.9%, <i>p</i> = 0.02). R0 resection rate was similar between groups. E-OSH and completed TSH had similar overall survival (5-year 38.2 vs. 31.8%), recurrence-free survival (3-year 17.6 vs. 17.7%), and recurrence sites. <b><i>Conclusions:</i></b> E-OSH is a safe alternative to TSH for multiple bilobar deep-located CLM. Whenever feasible, E-OSH should even be considered the preferred option because it has excellent safety and oncological outcomes equivalent to completed TSH, without the drop-out risk.
Radiation Exposure during Ureterorenoscopy and Laser Lithotripsy: An Analysis of Stone Characteristics
Authors: Hadjipavlou Marios , Lam Vincent , Seth Jai , Anjum Faqar , Sriprasad Seshadri 
Published: February 2018

<b><i>Introduction and Objectives:</i></b> Stone formers often have a chronic exposure to significant quantities of ionising radiation from radiological investigations and interventions. Predicting radiation exposure would allow the clinician to quantify expected cumulative radiation and find strategies to minimise exposure. We evaluated radiation exposure during ureteroscopy and laser lithotripsy (URS + LL) for a single stone episode and correlated the results to stone characteristics. <b><i>Method:</i></b> Data was collected retrospectively for all patients undergoing URS + LL in our institution over a 1 year period. Patients with multiple stones, staghorn stones or incomplete stone clearance were excluded to simplify the analysis. Patient characteristics, fluoroscopy data and stone characteristics were recorded. <b><i>Results:</i></b> We included 302 consecutive patients in the study. The majority of stones were located in the renal calyces/pelvis (54%) with the rest located in the upper (18%), middle (13%) and lower ureter (15%). Mean stone diameter was 9.9 mm (range 4–30 mm). Mean radiation exposure time during URS + LL was 44 s (range 12–119 s) with a mean total radiation exposure of 7.5 milligray (mGy; range 1.2–29.7 mGy). Renal stones were associated with 27% higher radiation exposure compared to ureteral stones (8.3 vs. 6.7 mGy; <i>p</i> = 0.02). There was a positive correlation between stone diameter and radiation exposure (Spearman’s correlation coefficient ρ = 0.28; <i>p</i> &#x3c; 0.001). Stones with diameter greater than 10 mm were associated with 37% higher radiation exposure compared to smaller stones (9.1 vs. 6.6 mGy; <i>p</i> &#x3c; 0.001). <b><i>Conclusion:</i></b> There is a direct correlation between stone burden, as well as location, and radiation exposure during URS + LL. Clinicians should consider strategies to reduce total radiation exposure in recurrent stone formers at risk of high radiation exposure by limiting screening time, using pulsed rather than continuous fluoroscopy, management with primary URS + LL, or using ultrasound guidance.