tbuckley/cabot-search huggingface dataset:
Aldolase A promotes proliferation and G<sub>1</sub>/S transition via the EGFR/MAPK pathway in non‐small cell lung cancer
Authors: Hailu Fu, Huijun Gao, Xiaoyu Qi, Lei Zhao, Donghua Wu, Yuxin Bai, Huimin Li, Xuan Liu, Jun Hu, Shujuan Shao
Journal: Cancer Communications (2018)

Our previous study demonstrated that aldolase A (ALDOA) is overexpressed in clinical human lung squamous cell carcinoma and that ALDOA promotes epithelial-mesenchymal transition and tumorigenesis. The present study aimed to explore the function of ALDOA in the modulation of non-small cell lung cancer (NSCLC) proliferation and cell cycle progression and the potential mechanism.ALDOA was knocked down by short hairpin RNA in H520 and H1299 cells. ALDOA was overexpressed with vectors carrying the full-length ALDOA sequence in H1299 and H157 cells. The proliferation capacities were assessed with immunohistochemical staining, Cell Counting Kit-8 and colony formation assays. The cell cycle distribution was examined by flow cytometry, and molecular alterations were determined by western blotting. Cell synchronization was induced with nocodazole. The stability of cyclin D1 mRNA was tested. The pyruvate kinase M2 and ALDOA protein distributions were examined. Aerobic glycolysis was evaluated with Cell Titer-Glo assay, glucose colorimetric assay and lactate colorimetric assay.ALDOA knockdown inhibited the proliferation and G1/S transition in H520 cells. Conversely, ALDOA overexpression promoted the proliferation and G1/S transition in H157 cells. The cell cycle synchronization assay showed that ALDOA expression increased in the G1 phase and G1/S transition. Furthermore, ALDOA knockdown reduced cyclin D1 expression by regulating epidermal growth factor receptor/mitogen-activated protein kinase (EGFR/MAPK) pathway. Similar results were found in H1299 and H157 cells. The inhibition of mitogen-activated protein kinase kinase 1/2 prompted the nuclear distribution of ALDOA. Additionally, ALDOA knockdown reduced nuclear distribution of PKM2, the extracellular lactate and intracellular adenosine triphosphate concentrations and elevated the extracellular glucose concentration.ALDOA contributed to activation of the EGFR/MAPK pathway, thus promoting cyclin D1 expression and enhancing proliferation and G1/S transition in NSCLC. Additionally, ALDOA facilitated NSCLC aerobic glycolysis.
Considering the Genetic and Epigenetic Signature of Early Adversity Within a Biopsychosocial Framework
Authors: Rachel Yehuda, Janine D. Flory
Journal: American Journal of Psychiatry (2018)

Is early exposure to adversity associated with a genetic or an epigenetic signature?At first glance, two articles in this issue-one from Peterson et al. ( 1), who conducted a genomewide association study for depression in a large sample of women ages 30-60, and the other from Marzi et al. ( 2), who measured genome-wide DNA methylation in a prospective twin cohort assessed at age 18-appear to say that it is not.Peterson et al. found that the occurrence of recurrent depression was associated with five genetic loci, but only in women who did not report a history of childhood adversity.In depressed women who did report early adversity, no loci were detected.These findings could lead a reader to the premature conclusion that depression with adversity is "nongenetic" and, by extension, that adversity is not associated with genetic antecedents.Similarly, Marzi et al. found no epigenetic signal in association with childhood victimization, as evaluated in real time at ages 5, 7, 10, 12, and 18.Interestingly, using retrospective reports of childhood victimization collected at age 18, two probes were identified, although co-twin analyses did not show an association between these probes and victimization severity.Marzi and colleagues' observations might lead to the conclusion that victimization is not affected by, nor does it affect, the epigenome.A second glance, however, leads to a different understanding of these findings.The first point to highlight is that a failure to identify a genetic or an epigenetic signature of victimization in a main effect analysis does not mean that adversity is not associated with genetic or epigenetic markers.Rather, it might be an indication of the necessity of directly examining, and accounting for, the moderating behavioral, psychiatric, and health effects of victimization.Thirty years of focused work on biological effects of trauma has shown that the subjective impact and biobehavioral consequences of trauma exposurenot just its presence or severity-must be considered in any investigation of biological associations with trauma exposure (3, 4).Indeed, victimization experiences predicted poor psychiatric outcomes in the same cohort (5) that Marzi et al. report on here, raising the possibility that the inclusion of those variables may have yielded a methylation signal in specific subtypes of victimized twins.In the Peterson et al. study, when the five loci detected in association with depression in women unexposed to childhood adversity were examined in the full sample, significant gene-by-environment interactions were observed.The combined power offered by
Sentinel lymph node biopsy using super magnetic iron oxide and an original magnetic probe in Japan.
Authors: Kanae Taruno, Tomoko Kurita, Katsutoshi Enokido, Seigo Nakamura, Masayuki Sekino, Moriaki Kusakabe, Hiroyuki Takei
Journal: Journal of Clinical Oncology (2018)

e12603 Background: Sentinel lymph node biopsy (SLNB) using combined radioisotope (RI) and blue dye is a gold standard technique for breast cancer surgery. A new SLNB technique using super magnetic iron oxide (SPIO) and a magnetic probe may resolve problems and limitations of the use of RI tracers. We conducted a clinical study which aimed to demonstrate non-inferiority of sentinel lymph node (SLN) detection rates by using a SPIO/magnetic probe system to the conventional RI technique in patients with breast cancer. This study was supported by AMED (Japan Agency for Medical Research and Development) research funds and was started at two institutions since May 2016. The novel magnetic probe is equipped with a permanent magnet and a magnetic sensor (Sci Rep 8, 1195, 2018). Methods: Both RI (99mTc) and SPIO (ferucarbotran, 540mg/1ml) were subcutaneously injected under the areola on the day before operation or in the morning of operation. We detected SLNs by using both the magnetic probe and a gamma probe. A primary endpoint of the study was to analyze the proportion of successful SLNB cases by the magnetic technique in comparison with the standard (RI and blue dye) technique. Over 180 cases were needed to prove non-inferiority of the magnetic method, based on an expected SLN identification rate 95% and a threshold rate 90% with higher than 80% power and one-sided α 0.05. We decided to judge the non-inferiority if the lower bound of 90% confidence interval (CI) of the rate is over the threshold. Results: 200 cases entered in this study. 4 cases were excluded because of the magnetic probe machine trouble during operation. A total of 196 cases were finally analyzed. In 186 of 196 cases at least one SLN was detected by both SPIO and RI. A concordance rate was 94.9%. In 10 and 4 cases, no SLN was detected by SPIO and by 99mTc, respectively. The SLN detection rates of SPIO and RI were 94.9% (186/196 cases, 90%CI 0.91-0.97) and 98.0% (192/196 cases, 90%CI 0.95-0.99%), respectively, and both lower bounds were over 90%. Conclusions: SLNB using SPIO and the new magnetic probe demonstrated non-inferiority to the standard RI technique. A magnetic technique of SLNB needs to be further evaluated for its efficacy and safety by larger studies. Clinical trial information: 31240.
Facilitating patient communication through understanding their social media use: A comparison by age groups.
Authors: Shayan Kassirian, Lawson Eng, Chelsea Paulo, Ilana Geist, Alexander Magony, Elliot Charles Smith, Mindy Liang, Dongyang Yang, Jennifer M. Jones, Shabbir M.H. Alibhai, Jackie Bender, M. Catherine Brown, Wei Xu, Abha A. Gupta, Geoffrey Liu
Journal: Journal of Clinical Oncology (2018)

71 Background: Social media and internet is increasingly used by patients for cancer education, which can affect provider-patient communication. Usage habits of the adolescent-young adult (AYA; aged &lt; 40 years), adult (age 40- &lt; 65 years), and geriatric cancer populations (age 65+ years) are likely different. Methods: Using age-specific sampling, cancer patients across all disease sites cross-sectionally were asked to complete a survey of demographics, health status, and social media/online resource use for cancer education. Clinical information was abstracted. Results: Of 429 approached, 320 participated (126 AYA, 128 adults, 66 elderly). Males comprised 44%; 72% had post-secondary education; 31% had household incomes of &gt; $100,000. Elderly patients were most likely to refuse participation (33% of elderly approached vs 16% AYA; p &lt; 0.001), with the most common reason being "I do not use internet resources/don't plan on using them"(96% of all elderly refusals with available data). Among respondents, the proportion who utilized the internet for cancer education was 76%, 76% and 70% in AYA, adults, and elderly, respectively (p &gt; 0.5). The use of social media tools in respondents was 49%, 40%, and 36%, respectively (p = 0.16 across age groups). While 75% of patients felt they could judge the quality of cancer-related information on the internet (no differences by age group, p &gt; 0.5), a significantly lower 43% (p &lt; 0.001) felt similarly confident to judge the quality of social media; AYA patients (49%) were numerically more likely to feel confident than seniors (36%; p = 0.16). Elderly were less likely to want online health record access (p = 0.015), treatment option (p = 0.042) and side effect education (p &lt; 0.001), future care plan (p &lt; 0.001) and wellness programs compared to others (p &lt; 0.001). Conclusions: Although cancer patients used social media frequently, confidence is lacking on the quality of cancer information obtained (across all age groups), while elderly perceive fewer benefits of using online/social media related to their cancer. Guidelines for patients on how to assess quality and appropriately use social media could help facilitate patient-provider communication.
Association between delayed gastric emptying and upper gastrointestinal symptoms: a systematic review and meta-analysis
Authors: Priya Vijayvargiya, Sina Jameie-Oskooei, Michael Camilleri, Victor Chedid, Patricia J Erwin, Mohammad Hassan Murad
Journal: Gut (2018)

The relationship between delayed gastric emptying and upper GI symptoms (UGI Sx) is controversial.To assess association between gastric emptying and UGI Sx, independent of treatment.We performed a systematic review and meta-analysis of the literature from 2007 to 2017, review of references and additional papers identified by content expert. We included studies evaluating the association between gastric emptying and nausea, vomiting, early satiety/postprandial fullness, abdominal pain and bloating. Covariate analyses included optimal gastric emptying test method, gastric emptying type (breath test or scintigraphy) and patient category. Meta-regression compared the differences based on type of gastric emptying tests.Systematic review included 92 gastric emptying studies (26 breath test, 62 scintigraphy, 1 ultrasound and 3 wireless motility capsule); 25 of these studies provided quantitative data for meta-analysis (15 scintigraphy studies enrolling 4056 participants and 10 breath test studies enrolling 2231 participants). Meta-regression demonstrated a significant difference between optimal and suboptimal gastric emptying test methods when comparing delayed gastric emptying with nausea and vomiting. On evaluating studies using optimal gastric emptying test methodology, there were significant associations between gastric emptying and nausea (OR 1.6, 95% CI 1.4 to 1.8), vomiting (OR 2.0, 95% CI 1.6 to 2.7), abdominal pain (OR 1.5, 95% CI 1.0 to 2.2) and early satiety/fullness (OR 1.8, 95% CI 1.2 to 2.6) for patients with UGI Sx; gastric emptying and early satiety/fullness in patients with diabetes; gastric emptying and nausea in patients with gastroparesis.The systematic review and meta-analysis supports an association between optimally measured delayed gastric emptying and UGI Sx.
HIF-prolyl hydroxylase 2 silencing using siRNA delivered by MRI-visible nanoparticles improves therapy efficacy of transplanted EPCs for ischemic stroke
Authors: Congxiao Wang, Gan Lin, Ying Luan, Jie Ding, Pei-cheng Li, Zhen Zhao, Cheng Qian, Gang Liu, Shenghong Ju, Gao-Jun Teng
Journal: Biomaterials (2018)
Pyruvate is a prospective alkalizer to correct hypoxic lactic acidosis
Authors: Ying Wang, Ya Huang, Jing Yang, Fang-Qiang Zhou, Lian Zhao, Hong Zhou
Journal: Military Medical Research (2018)

Type A lactic acidosis resulted from hypoxic mitochondrial dysfunction is an independent predictor of mortality for critically ill patients. However, current therapeutic agents are still in shortage and can even be harmful. This paper reviewed data regarding lactic acidosis treatment and recommended that pyruvate might be a potential alkalizer to correct type A lactic acidosis in future clinical practice. Pyruvate is a key energy metabolic substrate and a pyruvate dehydrogenase (PDH) activator with several unique beneficial biological properties, including anti-oxidant and anti-inflammatory effects and the ability to activate the hypoxia-inducible factor-1 (HIF-1α) - erythropoietin (EPO) signal pathway. Pyruvate preserves glucose metabolism and cellular energetics better than bicarbonate, lactate, acetate and malate in the efficient correction of hypoxic lactic acidosis and shows few side effects. Therefore, application of pyruvate may be promising and safe as a novel therapeutic strategy in hypoxic lactic acidosis correction accompanied with multi-organ protection in critical care patients.
An update on the Society for Immunotherapy of Cancer consensus statement on tumor immunotherapy for the treatment of cutaneous melanoma: version 2.0
Authors: Ryan J. Sullivan, Michael B. Atkins, John M. Kirkwood, Sanjiv S. Agarwala, Joseph I. Clark, Marc S. Ernstoff, Leslie Fecher, Thomas F. Gajewski, Brian Gastman, David H. Lawson, Jose Lutzky, David F. McDermott, Kim A. Margolin, Janice M. Mehnert, Anna C. Pavlick, Jon M. Richards, Krista M. Rubin, William Sharfman, Steven Silverstein, Craig L. Slingluff, Vernon K. Sondak, Ahmad A. Tarhini, John A. Thompson, Walter J. Urba, Richard L. White, Eric D. Whitman, F. Stephen Hodi, Howard L. Kaufman
Journal: Journal for ImmunoTherapy of Cancer (2018)

Cancer immunotherapy has been firmly established as a standard of care for patients with advanced and metastatic melanoma. Therapeutic outcomes in clinical trials have resulted in the approval of 11 new drugs and/or combination regimens for patients with melanoma. However, prospective data to support evidence-based clinical decisions with respect to the optimal schedule and sequencing of immunotherapy and targeted agents, how best to manage emerging toxicities and when to stop treatment are not yet available.To address this knowledge gap, the Society for Immunotherapy of Cancer (SITC) Melanoma Task Force developed a process for consensus recommendations for physicians treating patients with melanoma integrating evidence-based data, where available, with best expert consensus opinion. The initial consensus statement was published in 2013, and version 2.0 of this report is an update based on a recent meeting of the Task Force and extensive subsequent discussions on new agents, contemporary peer-reviewed literature and emerging clinical data. The Academy of Medicine (formerly Institute of Medicine) clinical practice guidelines were used as a basis for consensus development with an updated literature search for important studies published between 1992 and 2017 and supplemented, as appropriate, by recommendations from Task Force participants.The Task Force considered patients with stage II-IV melanoma and here provide consensus recommendations for how they would incorporate the many immunotherapy options into clinical pathways for patients with cutaneous melanoma.These clinical guidleines provide physicians and healthcare providers with consensus recommendations for managing melanoma patients electing treatment with tumor immunotherapy.
Combination of paclitaxel and a LAG-3 fusion protein (eftilagimod alpha), as a first-line chemoimmunotherapy in patients with metastatic breast carcinoma (MBC): Final results from the run-in phase of a placebo-controlled randomized phase II.
Authors: Francois P. Duhoux, Agnes Jager, Luc Yves Dirix, Manon Thirza Huizing, Guy Heinrich Maria Jerusalem, Peter Vuylsteke, Eveline De Cuypere, Doris Breiner, Christian Mueller, Chrystelle Brignone, Frederic Triebel
Journal: Journal of Clinical Oncology (2018)

1050 Background: Eftilagimod alpha (efti, previously IMP321) is a recombinant LAG-3Ig fusion protein that binds to MHC class II and mediates antigen-presenting cell (APC) activation followed by CD8 T-cell activation. The activation of the dendritic cell network with efti the day after chemotherapy may lead to stronger anti-tumor CD8 T cell responses. We report final results of the safety run-in of a phase IIb trial (NCT02614833) in patients (pts) with hormone receptor positive MBC receiving weekly paclitaxel as first line chemotherapy. Methods: In the safety run-in phase 15 pts with MBC received paclitaxel (80 mg/m2; D1, D8, D15; IV) in a 4-week cycle in conjunction with either 6 mg (n = 6; cohort 1) or 30 mg (n = 9; cohort 2) efti injections (D2 and D16; SC) for 6 cycles. Pts without progressive disease could continue for a maximum of 12 additional efti injections every 4 weeks. Blood samples for pharmacokinetics and immuno-monitoring were taken in cycle 1, 4 and 6. The primary endpoint was determination of the recommended phase 2 dose of this combination. Results: Between Jan and Oct 2016 15 pts (median age 53 years) were enrolled. A majority (67 %) of pts were pre-treated with hormonal therapy. Nine (67 %) pts had a serious adverse event, out of which 1 was related to paclitaxel (dizziness grade 3) and 1 to efti (cytokine release syndrome grade 1). No grade 4 and 4 grade 3 adverse events (AEs) in 4 pts were related to efti. Grade 1 and 2 injection site reactions were the most common efti related AEs and occurred in 14 pts (93 %). Increased number of circulating monocytes, dendritic cells and CD8 T cells as well as increased cellular activation were observed. This sustained (≥ 6 months) activation of the cellular response was associated with increased Th1 markers (IFN-g, CXCL10) levels in the plasma. Seven pts (47 %) had a partial response according to RECIST 1.1 (mean duration of 9 months). The disease control rate was 87 %. Conclusions: Thirty mg efti SC is the recommended phase 2 dose and is currently investigated in the ongoing phase II part of the study. Efti leads to a steady and sustainable APC and T cell activation. Clinical trial information: NCT02614833.
A hook effect-free immunochromatographic assay (HEF-ICA) for measuring the C-reactive protein concentration in one drop of human serum
Authors: Jusung Oh, Hyou-Arm Joung, Hyung Soo Han, Jong Kun Kim, Min-Gon Kim
Journal: Theranostics (2018)

The immunochromatographic (ICA) assay is a highly promising platform for rapid and simple detection of C-reactive protein (CRP) which is an indicator of the different phases of various diseases, as well as of inflammation and infection.However, the hook effect in the ICA assay limits the quantification of CRP levels at high CRP concentrations.Methods: In this study, we developed a hook effect-free immunochromatographic assay (HEF-ICA) to detect CRP over a wide concentration range.The hook effect results from the simultaneous reaction of an excess target antigens with both immobilized and labeled antibodies respectively.To reduce the potential occurrence of this simultaneous reaction, we separated the migration of the target antigen and gold nanoparticle (AuNP)-labeled antibodies on a nitrocellulose membrane and analyzed the time profiles by modifying the ICA structure.Results: The signal intensity of HEF-ICA was saturated at high CRP concentrations, without decreasing.The titration curve of HEF-ICA was adjusted with the Hill equation, and HEF-ICA was performed with the following parameters: limit of detection, 43 ng mL -1 ; dynamic range, 119 ng mL -1 to 100 µg mL -1 .The accuracy of the newly developed assay was evaluated using 33 clinical samples via comparison with a clinical chemistry analyzer.Conclusion: HEF-ICA enabled the measurement of a wide range of CRP concentrations without the hook effect, and was suitable for point-of-care testing with fingertip blood sampling, as only a minute sample volume (2.5 µL) was required.
Dynamic changes of interleukin 2 (IL-2) and circulating tumor cells (CTCs) in patients with advanced breast cancer (BCa) after systemic therapies.
Authors: Qiang Zhang, Lorenzo Gerratana, Lisa Flaum, Ami N. Shah, Brian Helfand, Youbin Zhang, William John Gradishar, Leonidas C. Platanias, Massimo Cristofanilli
Journal: Journal of Clinical Oncology (2018)

1090 Background: CTCs play a critical role in BCa metastasis and worse prognosis even after systemic treatments such as chemotherapy and biological therapy. The mechanisms that contribute to CTCs migration and tumor aggressiveness remain unknown. Herein, we report a novel finding of the correlation between plasma IL-2 and the changes of CTC for BCa patients after therapies. Methods: Duplicate whole blood samples (7.5ml/each) were collected in EDTA tubes from 43 patients with stage III/IV BCa patients before (baseline, BL) or 3 months after (first evaluation, FE) systemic therapies respectively from patients treated at NMH. CTC enrichment and enumeration were performed in FDA approved CELLTRACKS ANALYZERII System and were linked with clinical database. The CTCs were classified as CK+, EpCAM+, DAPI+ and CD25-. ELISA for IL-2 was performed by using patients' plasma. Kruskal-Wallis test was used for statistics. Results: CTCs were detected in 23 patients at BL and 21 patients at FE of blood draws respectively. CTCs count increased in 12 patients (Group 1: from 102.9 to 213.3), decreased in 14 patients (Group 2: from 23 to 13.6) and remained unchanged as 0 in 17 patients (Group 3) respectively when BL was compared to the FE. The corresponding changes of IL-2 were -17.4pg/ml, 8.04pg/ml and -4.59pg/ml in Group 1, 2 and 3 respectively. The BL level of IL-2 in Group 1 is significantly higher than the other two groups (p = 0.027), and decreased of CTCs is associated with increased IL-2 (P < 0.01), while decreased IL-2 in FE level is associated with increased of CTCs after therapy in whole population (p < 0.001). More important, IL-2 dropped significantly in patients with CTC stably ≥5 or who experienced a rise in CTC ≥5 at the FE compared to the BL time point (p < 0.001). Conclusions: The study demonstrated for the first time a reverse correlation between IL-2 level and CTCs count. The data suggest that the more aggressive BCa (CTC≥5) induce the immune response (high levels of IL2 at baseline), but subsequently the IL2 level will decrease in patients that fail to benefit from treatment. We propose that surveillance of immune cytokine will help to understand advanced BCa prognosis and predict treatment benefit.