tbuckley/cabot-search huggingface dataset:
Intrahost Genetic Diversity of Bacterial Symbionts Exhibits Evidence of Mixed Infections and Recombinant Haplotypes
Authors: Shelbi L. Russell, Colleen M. Cavanaugh
Journal: Molecular Biology and Evolution (2017)

Even the simplest microbial-eukaryotic mutualisms are comprised of entire populations of symbionts at the level of the host individual. Early work suggested that these intrahost populations maintain low genetic diversity as a result of transmission bottlenecks or to avoid competition between symbiont genotypes. However, the amount of genetic diversity among symbionts within a single host remains largely unexplored. To address this, we investigated the chemosynthetic symbiosis between the bivalve Solemya velum and its intracellular bacterial symbionts, which exhibits evidence of both vertical and horizontal transmission. Intrahost symbiont populations were sequenced to high coverage (200-1,000×). Analyses of nucleotide diversity revealed that the symbiont genome sequences were largely homogeneous within individual host specimens, consistent with vertical transmission, except for particular regions that were polymorphic in ∼20% of host specimens. These variant sites were also found segregating in other host individuals from the same population, colocalized to several regions of the genome, and consistently co-occurred on the same short read pairs (derived from the same chromosome). These results strongly suggest that these variant haplotypes originated through recombination events, potentially during prior mixed infections or in the external environment, rather than as novel mutations within symbiont populations. This abundant genetic diversity could have a profound influence on symbiont evolution as it provides the opportunity for selection to limit the extent of reductive genome evolution commonly seen in obligate intracellular bacteria and to enable the evolution of adaptive genotypes.
FKBP38 works as a novel link between cell death and cell cycle through the ROS-mediated damages on the mitochondrial membrane potential
Authors: Lin Feng, Ho Sup Yoon
Journal: Clinical Cancer Research (2007)

B25  Apoptosis and cell cycle are two fundamental physiological activities inside cells. The balance between these two biological processes is essential to maintain the normal embryonic development and tissue homeostasis. Bcl-2 was reported previously involved in regulating cell cycle progression. Here by using RNA interference and flow cytometry, we explored the Bcl-2-binding protein, FK506-binding protein (FKBP38) in the regulation of cell cycle progression. Although both the removal of Bcl-2 and FKBP38 initiated cell cycle progression, Bcl-2 indicated a more directly protective role on the mitochondrial membrane. Yet, silencing FKBP38 caused a significant increase of S-phase cell populations, which was responsible for a dramatic generation of ROS. And this high-level ROS showed a damage effect on the mitochondrial membrane potential (MMP). This damage on the MMP could be reversed by the antioxidant Tiron. Thus, we concluded that FKBP38 acted as a novel link between cell cycle and apoptosis through the ROS-mediated damages on the mitochondrial membrane potential.
Assessment of EGFR mutation status in matched plasma and tumor tissue of NSCLC patients.
Authors: Qin Feng
Journal: Journal of Clinical Oncology (2017)

e20032 Background: Tumor tissue is currently used for EGFR testing non-small cell lung cancer (NSCLC) patients, but the detection of circulating tumor DNA (ctDNA) is being actively investigated as a new method for the detection and longitudinal monitoring of actionable mutations in plasma samples. Around 30% patients with EGFR mutation presented inconsistent status of EGFR mutation between in tissues and plasma. We compared EGFR mutation detection in circulating tumor DNA from blood to that in matched tissue. Methods: EGFR mutation status were assessed by the Human EGFR Gene Mutations Detection Kit (Beijing ACCB Biotech Ltd.) both in tissue and plasma. Retrospective analysis to evaluate the concordance of tissue and plasma EGFR determination for assessing eligibility for EGFR-TKIs therapy in NSCLC patients. 10 mL tubes of blood were collected from patients who never had been treated by EGFR TKI, and plasma circulating tumor DNA were extracted from plasma by Biomark Circulating DNA Kit. Qubit2.0 Fluorometer was used to make plasma circulating DNA tumor quantitation. The concentration of final DNA sample is ≦2ng/μl. Results: A total of 224 NSCLC patients were detected by Amplification Refractory Mutation System (ARMS), with 92 tissue positive and 49 blood positive. Results showed 53.3% sensitivity in overall samples, but 81.4% sensitivity in ⅢB~Ⅲ patients. The specificity is 100%. Conclusions: The high sensitivity and specificity between tissue and plasma EGFR determination supports the blood-based EGFR mutation testing to determinate the eligibility of NSCLC patients for EGFR-TKIs treatment, especialy in ⅢB~Ⅲ NSCLC patients. Blood, in particular plasma, is a good screening substitute when tumor tissue is absent or insufficient for testing EGFR mutations to guide EGFR TKIs treatment in patients with NSCLC. EGFR mutation positivity in blood could be used to recommend EGFR TKIs treatment, but the blood negativity should be confirmed with other sample, biopsy tissue, pleural effusion, etc..
Safety and efficacy of low-dose decitabine primed chemotherapy in patients with chemoresistant relapsed/refractory gastrointestinal cancers
Authors: Meixia Chen, Jing Nie, Yang Liu, Xiang Li, Yan Zhang, Malcolm Brock, Kaichao Feng, Zhiqiang Wu, Xiaolei Li, Lu Shi, Suxia Li, Mingzhou Guo, Qian Mei, Weidong Han
Journal: Annals of Oncology (2017)
Immediate moxifloxacin hypersensitivity: Is there more than currently meets the eye?
Authors: A. L. Van Gasse, V. Sabato, A. P. Uyttebroek, J. Elst, M. A. Faber, M. M. Hagendorens, C. Mertens, C. H. Bridts, L. S. De Clerck, D. G. Ebo
Journal: Allergy (2017)

Immediate drug hypersensitivity reactions (IDHR) to moxifloxacin constitute a pathomechanistic conundrum and a diagnostic challenge. Our objective was to study whether simultaneous phenotyping and quantification of histamine release might add to our knowledge about the basophil activation properties of moxifloxacin and constitute a reliable diagnostic aid. Fifteen patients with an IDHR to moxifloxacin and nine moxifloxacin challenged controls were selected. All had a basophil activation test (BAT) with moxifloxacin. Flow cytometric analysis of basophil responses implied labeling for CD63, CD203c, and intracellular histamine. Unlike tolerant challenged controls, basophilic upregulation of CD203c in response to moxifloxacin was observed in seven of 15 patients. Only two of these seven patients demonstrated appearance of CD63 and release of histamine. In the remainder eight patients, no basophil responses were demonstrable. In conclusion, immediate hypersensitivity to moxifloxacin might involve mechanisms difficult to capture by traditional CD63-/CD203c-based BAT. Deciphering the complexity of quinolone IDHR seems mandatory.
Cancer Screening Recommendations and Clinical Management of Inherited Gastrointestinal Cancer Syndromes in Childhood
Authors: Maria Isabel Achatz, Christopher C. Porter, Laurence Brugières, Harriet Druker, Thierry Frebourg, William D. Foulkes, Christian P. Kratz, Roland P. Kuiper, Jordan R. Hansford, Hector Salvador Hernandez, Katherine L. Nathanson, Wendy K. Kohlmann, Leslie Doros, Kenan Onel, Kami Wolfe Schneider, Sarah R. Scollon, Uri Tabori, Gail E. Tomlinson, D. Gareth R. Evans, Sharon E. Plon
Journal: Clinical Cancer Research (2017)

Hereditary gastrointestinal cancer predisposition syndromes have been well characterized, but management strategies and surveillance remain a major challenge, especially in childhood. In October 2016, the American Association for Cancer Research organized the AACR Childhood Cancer Predisposition Workshop in which international experts in care of children with a hereditary risk of cancer met to define surveillance strategies and management of children with cancer predisposition syndromes. In this article, we review the current literature in polyposis syndromes that can be diagnosed in childhood and may be associated with an increased incidence of gastrointestinal neoplasms and other cancer types. These disorders include adenomatous polyposis syndromes (APC and MUTYH), juvenile polyposis coli (BMPR1A and SMAD4), Peutz-Jeghers Syndrome (STK11/LKB1), and PTEN hamartoma tumor syndrome (PHTS; PTEN), which can present with a more limited juvenile polyposis phenotype. Herein, the panel of experts provides recommendations for clinical diagnosis, approach to genetic testing, and focus on cancer surveillance recommendations when appropriate during the pediatric period. We also review current controversies on genetic evaluation of patients with hepatoblastoma and indications for surveillance for this tumor. Childhood cancer risks and surveillance associated with disorders involving the mismatch repair genes, including Lynch syndrome and constitutional mismatch repair deficiency (CMMRD), are discussed elsewhere in this series. Clin Cancer Res; 23(13); e107-e14. ©2017 AACRSee all articles in the online-only CCR Pediatric Oncology Series.
PD-L1 hotspot in tumor-infiltrating lymphocytes of radically treated esophageal squamous cell carcinoma: Pattern of recurrence and long-term clinical outcomes
Authors: K.O. Lam, A.W.I. Lo, H.C.W. Choi, Ho Issac, B.T.T. Law, W.L. Chan, V.H.F. Lee, So Tsz Him, C.L. Chiang, S.Y. Chan, D.K.H. Tong, D.L.W. Kwong, S.Y.K. Law
Journal: Annals of Oncology (2017)
The Efficacy of Novel CFTR Inhibitors on the Secretory Funtion of Human Colonic Mucosa
Authors: A Patel, DI Bovell, AD Corbett, RJ Holdsworth
Journal: Endoscopy (2006)

Aims: To examine the efficacy of the novel Cystic Fibrosis Transmembrane Regulator (CFTR) inhibitors CFTR inh-172 and GlyH-101 on secretory responses to carbachol in human colonic mucosa.
Anti-Thrombin III Inhibits Adhesion of Sickle Red Blood Cells and Leukocytes to the Endothelium in a Sickle Cell Mouse Model: Potential Therapeutic Application for Vaso-Occlusive Episodes
Authors: Diana R. Gutsaeva, Nianlan Yang, James B Parkerson, Haiyan Xiao, Shobha Yerigenahally, Carol Dickerson, Wan Jin Jahng, Steffen E. Meiler, Manuela Bartoli
Journal: Blood (2016)
Cutaneous Leishmaniasis Induces a Transmissible Dysbiotic Skin Microbiota that Promotes Skin Inflammation
Authors: Ciara Gimblet, Jacquelyn S. Meisel, Michael A. Loesche, Stephen D. Cole, Joseph Horwinski, Fernanda O. Novais, Ana M. Misic, Charles W. Bradley, Daniel P. Beiting, Shelley C. Rankin, Lucas P. Carvalho, Edgar M. Carvalho, Phillip Scott, Elizabeth A. Grice
Journal: Cell Host & Microbe (2017)
Relationship of the microRNA-223/FBXW7/MCL1 pathway and the sensitivity of HER2-positive gastric cancer cells to trastuzumab.
Authors: Eto Kojiro, Masaaki Iwatsuki, Takatsugu Ishimoto, Hideo Baba
Journal: Journal of Clinical Oncology (2014)

e22208 Background: A recent large-scale phase III study (the ToGA trial) demonstrated the significant efficacy of trastuzumab (Tra) in addition to chemotherapy in patients with HER2-positive gastric cancer (GC). However, resistance to Tra has become a problem in breast cancer. F-box and WD repeat domain-containing 7 (FBXW7) is the substrate recognition components of an evolutionarily conserved SCF-type ubiquitin ligase complexe, which has been well characterized and shown to have important roles in regulating the stability of multiple oncoprotein substrates. Therefore, FBXW7 is recognized to be one of the major causes of drug resistance. The aim of the current study is to clarify the novel microRNA (miR)-FBXW7 pathway regulating resistance to Tra. Methods: Using 5 GC cell lines, we examined the following items in vitro. 1. We examined the status of FBXW7 expression by qRT-PCR. 2. We established the Tra resistance GC cell line with continuous Tra administration. Parent GC cell line and resistance GC cell line are subjected to miR PCR array. 3. We focused on miR223-FBXW7/MCL1 pathway. We examined the status of HER2, miR223, FBXW7, and its target gene MCL1 expression by up or down regulation of miR-223 in GC cell lines. 4. We investigated whether the miR-223-FBXW7 pathway can affect the resistance of Tra. Results: FBXW7 and miR-223 expression showed inverse correlation. Moreover, miR-223 expression was increased and FBXW7 expression was decreased whereas MCL1 expression, downstream targets of FBXW7, was increased while no significant change was observed both in HER2 and p-HER2 in GC Tra resistance cells. Overexpression of miR-223 decreased FBXW7 expression persisting HER2 and p-HER2 expression and can induce the resistance of Tra. The suppression of miR-223 increased FBXW7 expression persisting HER2 and p-HER2 expression and can simultaneously restore the sensitivity of Tra. Conclusions: Our current study revealed for the first time that regulated the sensitivity of HER2-positive GC cell line to Tra. These findings suggest that this pathway may be crucial to the mechanism of resistance to Tra in GC, which may lead to the development of individualized treatment in clinical practice.
Enhanced recovery after surgery (ERAS) program in patients undergoing major surgery for gastrointestinal cancer: Results of a 6-year clinical study
Authors: Vasileios Alivizatos, Pavlos Athanasopoulos, Georgia Korfiati, George Tzouvekas, Panagiota Demetriou, Evangelia Papageorgiou, Athina Kanellopoulou
Journal: Annals of Oncology (2017)
Children with NCI Standard Risk Acute Lymphoblastic Leukemia (ALL) and TEL-AML1 or Favorable Chromosome Trisomies Are Almost Certain to Be Cured with Graduated Intensity Therapy: Results of the CCG - 1991 Study.
Authors: Yousif Matloub, Bruce C. Bostrom, Anne L Angiolillo, Meenakshi Devidas, Nyla A. Heerema, Julie M. Gastier-Foster, Stephen P Hunger, Harland Sather, Stephen Linda, William L. Carroll, James B Nachman, Paul S. Gaynon
Journal: Blood (2009)
Oxygen Enhanced Optoacoustic Tomography (OE-OT) Reveals Vascular Dynamics in Murine Models of Prostate Cancer
Authors: Michal R Tomaszewski, Isabel Quiros Gonzalez, James Pb O'Connor, Oshaani Abeyakoon, Geoff Jm Parker, Kaye J Williams, Fiona J Gilbert, Sarah E Bohndiek
Journal: Theranostics (2017)

Poor oxygenation of solid tumours has been linked with resistance to chemo- and radio-therapy and poor patient outcomes, hence non-invasive imaging of oxygen supply and demand in tumours could improve disease staging and therapeutic monitoring. Optoacoustic tomography (OT) is an emerging clinical imaging modality that provides static images of endogenous haemoglobin concentration and oxygenation. Here, we demonstrate oxygen enhanced (OE)-OT, exploiting an oxygen gas challenge to visualise the spatiotemporal heterogeneity of tumour vascular function. We show that tracking oxygenation dynamics using OE-OT reveals significant differences between two prostate cancer models in nude mice with markedly different vascular function (PC3 & LNCaP), which appear identical in static OT. LNCaP tumours showed a spatially heterogeneous response within and between tumours, with a substantial but slow response to the gas challenge, aligned with
A painful dilemma? Analgesic use in sport and the role of anti-doping
Authors: Alan Vernec, Andrew Pipe, Andrew Slack
Journal: British Journal of Sports Medicine (2017)

How clinicians should address the use and abuse of analgesics in sport has been a focus of debate for many years. Concern for an athlete’s health and a desire to prevent unfair distortion of performance underlie any discussion of this issue. In 1967 the original IOC list of prohibited substances specifically identified ‘Narcotic Analgesics’ as being prohibited in sport. The 2017 WADA Prohibited List (List) mandates that ‘Narcotics’ and ‘Cannabinoids’ are prohibited ‘In-Competition’. More commonly used analgesics, including non-steroidal anti-inflammatory drugs, paracetamol, local anaesthetics, and some weak opioids such as tramadol and codeine are not prohibited. No well-defined boundary separates either the health risk or ergogenic potential of cannabinoids and narcotics versus the more commonly used analgesics.

Should more analgesics be added to the List or should narcotics and cannabis be removed? Is the use of pain medication doping? As defined by Article 2 of the World Anti-Doping Code (Code),1 doping is defined, inter alia, as the presence, use, possession or trafficking of a prohibited substance. This leads one to query: what are the key determinants for inclusion of a substance on the List? The Code criteria for the …
Ibrutinib Represents a Novel Class of Immune Modulating Therapeutics That Enhances the Survival of Activated T Cells in Vitro and In Vivo through a Non-BTK Mediated Mechanism
Authors: Meixiao Long, Kyle A. Beckwith, Priscilla Do, Mundy L Bethany, Gordon Gordon, Amy M. Lehman, Kami J. Maddocks, Carolyn Cheney, Jeffrey Jones, Leslie A. Andritsos, Farrukh T. Awan, Joseph A. Fraietta, Carl H June, Marcela V. Maus, Jennifer A. Woyach, Michael A. Caligiuri, Amy J. Johnson, Natarajan Muthusamy, John C. Byrd
Journal: Blood (2016)
Assessment of the Efficacy of Neoadjuvant Chemoradiotherapy in Rectal Cancer. Experience of an Irish Specialist Colorectal Unit
Authors: E Nzewi, E Boyle, D O'Riordain, P Neary, F Keane
Journal: Endoscopy (2006)

Aims: Neoadjuvant Chemoradiotherapy reduces the local recurrence rates in stage II and III rectal cancers. We evaluated the preoperative staging modalities and efficacy of neoadjuvant treatment in rectal cancer patients in our unit.
Photodynamic efficacy via modulation of signal pathways on chemoresistant small cell lung cancer (SCLC) cells
Authors: Christine Yow, M.R. Hamblin
Journal: Clinical Cancer Research (2007)

A25    Introduction:  Lung cancer is the leading cause of cancer death worldwide. Small cell lung cancer (SCLC) is associated with the poorest prognosis. Photodynamic therapy (PDT) is a new approach of cancer treatment. It works by generating singlet oxygen to induce cancer cell death in the presence of photosensitizers, light and oxygen. Photosensitizer - NPe6 may be useful for treating SCLC patients.   Aims:  To evaluate the anti-tumour effect and mechanism of the photosensitizer NPe6 - PDT in chemo-resistant cell line H69AR SCLC.   Method:  The optimal uptake of NPe6 in H69AR cells was measured by flowcytometer. Phototoxicity of NPe6-PDT to the cells was evaluated by automated cell viability analysis. The expression of tumor suppressor protein p53, the anti-apoptotic protein BCl 2 , p38 mitogen-activated protein kinase  (p38 MAPK) and c-jun N-terminal protein kinases (JNKs) were analyzed by Western blot. Morphological apoptotic changes in H69AR cells after treatment were determined by DAPI under microscopic examination.   Results:  The optimal cellular uptake of NPe6 was at 4 hours incubation. The phototoxicity of NPe6-PDT induced 75% killing in H69AR cells at 20μg/mL and 4 J/cm 2 . The expression of BCl 2  was down-regulated while the level of p53 remained after treatment. The expressions of phosphorylated p38 MAPK and JNK proteins were also down-regulated post-PDT treatment. Up to 50% of cells at LD 75 .showed condensed nucleus using DAPI nuclear stain, reflecting cells undergoing apoptosis.   Conclusion:  NPe6-PDT is effective to H69AR cells causing death through apoptosis. It may be mediated by suppressing the anti-apoptotic protein BCl 2  expression and down-regulating the phosphorylated p38MAPK and JNKs. Further cellular protein modulations after treatment will be elucidated.
The Final Report of a Phase I/II Study of Panobinostat in Combination with ICE (Ifosfamide, Carboplatin and Etoposide) in Patients (pts) with Relapsed or Refractory (R/R) Classical Hodgkin Lymphoma (cHL)
Authors: Bei Hu, Anas Younes, Linda Claret, Lei Feng, Jason R. Westin, Nathan Fowler, Sattva Neelapu, Fredrick B. Hagemeister, Maria Alma Rodriguez, Felipe Samaniego, Luis E. Fayad, Loretta J. Nastoupil, Amanda R Copeland, Michelle A Fanale, Yasuhiro Oki
Journal: Blood (2016)
Electrostimulated Release of Neutral Drugs from Polythiophene Nanoparticles: Smart Regulation of Drug–Polymer Interactions
Authors: Anna Puiggalí‐Jou, Paolo Micheletti, Francesc Estrany, Luis J. del Valle, Carlos Alemán
Journal: Advanced Healthcare Materials (2017)

Poly(3,4‐ethylenedioxythiophene) (PEDOT) nanoparticles are loaded with curcumin and piperine by in situ emulsion polymerization using dodecyl benzene sulfonic acid both as a stabilizer and a doping agent. The loaded drugs affect the morphology, size, and colloidal stability of the nanoparticles. Furthermore, kinetics studies of nonstimulated drug release have evidenced that polymer···drug interactions are stronger for curcumin than for piperine. This observation suggests that drug delivery systems based on combination of the former drug with PEDOT are much appropriated to show an externally tailored release profile. This is demonstrated by comparing the release profiles obtained in presence and absence of electrical stimulus. Results indicate that controlled and time‐programmed release of curcumin is achieved in a physiological medium by applying a negative voltage of −1.25 V to loaded PEDOT nanoparticles.
Abstract 260: A miRNA-Hippo Pathway Promotes Cardiac Conduction System Regeneration
Authors: Jun Wang, James F Martin
Journal: Circulation Research (2014)

The cardiac conduction system (CCS) is required for initiating and maintaining regular rhythmic heartbeats and CCS defects can give rise to cardiac arrhythmia, a leading cause for morbidity worldwide. Given the poor self-repair potential in the adult human CCS, it is critical to elucidate the molecular mechanisms limiting CCS regeneration to facilitate developing efficient cardiovascular therapies. microRNAs (miRs) are small non-coding RNAs that repress gene expression post-transcriptionally. The miR-17-92 cluster can induce cardiomyocyte proliferation and regeneration. Hippo signaling, an ancient organ size control pathway, represses cardiomyocyte proliferation and regeneration. Here we found that both miR-17-92 and Hippo signaling were active in CCS. Disruption of either miR-17-92 or Hippo signaling in heart gave rise to cardiac arrhythmias in mice. Notably, miR-17-92 regulates Hippo signaling through repressing Lats2, a core Hippo pathway component. In miR-17-92 null mutant hearts, up-regulated Lats2 led to increased Hippo pathway activity. Moreover, we performed chromatin immunoprecipitation deep sequencing (ChIP-Seq) using YAP, the Hippo signaling effector, which suggested that Hippo signaling regulates genes involved in CCS homeostasis. Together, we propose a novel miR-Hippo genetic pathway that promotes CCS regeneration.
KEYNOTE-059 cohort 3: safety and efficacy of pembrolizumab monotherapy for first-line treatment of patients (pts) with PD-L1-positive advanced gastric/gastroesophageal (G/GEJ) cancer
Authors: V. Catenacci Daniel, Zev Wainberg, S. Fuchs Charles, Marcelo Garrido, Yung-Jue Bang, Kei Muro, Mary Savage, Jiangdian Wang, Minori Koshiji, P. Dalal Rita, Yoon-Koo Kang
Journal: Annals of Oncology (2017)
Prospective evaluation of PROMs and acute toxicity in VMAT planned radiotherapy for anal cancer and relation to planning constraints
Authors: Camilla Kronborg, Eva Serup-Hansen, Annette Schouboe, Cecilie Lefevre Anna, Eva Wilken, Jolanta Hansen, Lars Nyvang, Karen-Lise Spindler
Journal: Annals of Oncology (2017)
Novel variants in NUDT15 and thiopurine intolerance in children with acute lymphoblastic leukemia from diverse ancestry
Authors: Takaya Moriyama, Yung-Li Yang, Rina Nishii, Hany Ariffin, Chengcheng Liu, Ting-Nien Lin, Wenjian Yang, Dong-Tsamn Lin, Chih-Hsiang Yu, Shirley Kham, Ching-Hon Pui, William E. Evans, Sima Jeha, Mary V. Relling, Allen Eng-Juh Yeoh, Jun J. Yang
Journal: Blood (2017)