tbuckley/cabot-search huggingface dataset:
Ethics and the Underreporting of Research Biopsy Findings in Clinical Trials
Authors: Michael J. Overman, Lee M. Ellis, Steven Joffe
Journal: JAMA Oncology (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Distinct, IgG1-driven antibody response landscapes demarcate individuals with broadly HIV-1 neutralizing activity
Authors: Claus Kadelka, Thomas Liechti, Hanna Ebner, Merle Schanz, Peter Rusert, Nikolas Friedrich, Emanuel Stiegeler, Dominique L. Braun, Michael Huber, Alexandra U. Scherrer, Jacqueline Weber, Therese Uhr, Herbert Kuster, Benjamin Misselwitz, Matthias Cavassini, Enos Bernasconi, Matthias Hoffmann, Alexandra Calmy, Manuel Battegay, Andri Rauch, Sabine Yerly, Vincent Aubert, Thomas Klimkait, Jürg Böni, Roger D. Kouyos, Huldrych F. Günthard, Alexandra Trkola
Journal: The Journal of Experimental Medicine (2018)

Understanding pathways that promote HIV-1 broadly neutralizing antibody (bnAb) induction is crucial to advance bnAb-based vaccines. We recently demarcated host, viral, and disease parameters associated with bnAb development in a large HIV-1 cohort screen. By establishing comprehensive antibody signatures based on IgG1, IgG2, and IgG3 activity to 13 HIV-1 antigens in 4,281 individuals in the same cohort, we now show that the same four parameters that are significantly linked with neutralization breadth, namely viral load, infection length, viral diversity, and ethnicity, also strongly influence HIV-1–binding antibody responses. However, the effects proved selective, shaping binding antibody responses in an antigen and IgG subclass–dependent manner. IgG response landscapes in bnAb inducers indicated a differentially regulated, IgG1-driven HIV-1 antigen response, and IgG1 binding of the BG505 SOSIP trimer proved the best predictor of HIV-1 neutralization breadth in plasma. Our findings emphasize the need to unravel immune modulators that underlie the differentially regulated IgG response in bnAb inducers to guide vaccine development.
The Case | A 69-year-old man with bladder carcinoma and renal lesions
Authors: Pierre Isnard, Hoang Minh Tran, Marie-Bénédicte Le Stang, Perrine Parize, Arnaud Méjean, Dominique Joly, Jean-Michel Correas, Marion Rabant, Mohamad Zaidan
Journal: Kidney International (2018)
MMP1/PAR1/SP/NK1R paracrine loop modulates early perineural invasion of pancreatic cancer cells
Authors: Chumei Huang, Yaqing Li, Yubo Guo, Zuoquan Zhang, Guoda Lian, Yinting Chen, Jian Li, Yonghui Su, Jiajia Li, Kege Yang, Shaojie Chen, Hong Su, Kaihong Huang, Linjuan Zeng
Journal: Theranostics (2018)

The molecular mechanism of perineural invasion (PNI) is unclear, and insufficient detection during early-stage PNI in vivo hampers its investigation. We aimed to identify a cytokine paracrine loop between pancreatic ductal adenocarcinoma (PDAC) cells and nerves and established a noninvasive method to monitor PNI in vivo. Methods: A Matrigel/ dorsal root ganglia (DRG) system was used to observe PNI in vitro, and a murine sciatic nerve invasion model was established to examine PNI in vivo. PNI was assessed by MRI with iron oxide nanoparticle labeling. We searched publicly available datasets as well as obtained PDAC tissues from 30 patients to examine MMP1 expression in human tumor and non-tumor tissues. Results: Our results showed that matrix metalloproteinase-1 (MMP1) activated AKT and induced protease-activated receptor-1 (PAR1)-expressing DRG to release substance P (SP), which, in turn, activated neurokinin 1 receptor (NK1R)-expressing PDAC cells and enhanced cellular migration, invasion, and PNI via SP/NK1R/ERK. In animals, hind limb paralysis and a decreased hind paw width were observed approximately 20 days after inoculation of cancer cells in the perineurium. MMP1 silencing with shRNA or treatment with either a PAR1 or an NK1R antagonist inhibited PNI. MRI detected PNI as early as 10 days after implantation of PDAC cells. PNI also induced PDAC liver metastasis. Bioinformatic analyses and pathological studies on patient tissues corroborated the clinical relevance of these findings. Conclusion: In this study, we provided evidence that the MMP1/PAR1/SP/NK1R paracrine loop contributes to PNI during the early stage of primary tumor formation. Furthermore, we established a sensitive and non-invasive method to detect nerve invasion using iron oxide nanoparticles and MRI.
Prophylactic Cranial Irradiation Versus Observation in Radically Treated Stage III Non–Small-Cell Lung Cancer: A Randomized Phase III NVALT-11/DLCRG-02 Study
Authors: Dirk De Ruysscher, Anne-Marie C. Dingemans, John Praag, Jose Belderbos, Caroline Tissing-Tan, Judith Herder, Tjeerd Haitjema, Fred Ubbels, Frank Lagerwaard, Sherif Y. El Sharouni, Jos A. Stigt, Egbert Smit, Harm van Tinteren, Vincent van der Noort, Harry J.M. Groen
Journal: Journal of Clinical Oncology (2018)

Purpose The purpose of the current study was to investigate whether prophylactic cranial irradiation (PCI) reduces the incidence of symptomatic brain metastases in patients with stage III non–small-cell lung cancer (NSCLC) treated with curative intention. Patients and Methods Patients with stage III NSCLC—staged with a contrast-enhanced brain computed tomography or magnetic resonance imaging—were randomly assigned to either observation or PCI after concurrent/sequential chemoradiotherapy with or without surgery. The primary end point—development of symptomatic brain metastases at 24 months—was defined as one or a combination of key symptoms that suggest brain metastases—signs of increased intracranial pressure, headache, nausea and vomiting, cognitive or affective disturbances, seizures, and focal neurologic symptoms—and magnetic resonance imaging or computed tomography demonstrating the existence of brain metastasis. Adverse effects, survival, quality of life, quality-adjusted survival, and health care costs were secondary end points. Results Between 2009 and 2015, 175 patients were randomly assigned: 87 received PCI and 88 underwent observation only. Median follow-up was 48.5 months (95% CI, 39 to 54 months). Six (7.0%) of 86 patients in the PCI group and 24 (27.2%) of 88 patients in the control group had symptomatic brain metastases ( P = .001). PCI significantly increased the time to develop symptomatic brain metastases (hazard ratio, 0.23; [95% CI, 0.09 to 0.56]; P = .0012). Median time to develop brain metastases was not reached in either arm. Overall survival was not significantly different between both arms. Grade 1 and 2 memory impairment (26 of 86 v seven of 88 patients) and cognitive disturbance (16 of 86 v three of 88 patients) were significantly increased in the PCI arm. Quality of life was only decreased 3 months post-PCI and was similar to the observation arm thereafter. Conclusion PCI significantly decreased the proportion of patients who developed symptomatic brain metastases with an increase of low-grade toxicity.
Correction to: Redefining mouse transgenesis with CRISPR/Cas9 genome editing technology
Authors: Gaetan Burgio
Journal: Genome biology (2018)

In the recent Research Highlight [1], it has been highlighted that part b of Fig. 1 was incorrectly labelled as "sgRNA + tracrRNA" instead of "sgRNA (crRNA + tracrRNA)". An updated Figure 1, including also the amended figure legend has therefore been provided below.
Abstract #4284: Blockade of VEGFR2/KDR increases malignancy in human epithelial ovarian carcinoma
Authors: Sirin Adham, Ifat Sher, Brenda L. Coomber
Journal: Cancer Research (2009)

Human epithelial ovarian carcinoma (EOC) is the most lethal neoplasm affecting the female genital tract. Vascular Endothelial Growth Factor (VEGF) and its tyrosine kinase receptor KDR (VEGFR2) are overexpressed in these lesions. We previously demonstrated that this signaling loop provides a survival pathway for human EOC growth in suspension, similar to what would occur in ascites fluid that accumulates in the peritoneal cavity of the patient. Chemoresistance is a major problem for successful therapy of this cancer, however, some progress has recently been made using bevacizumab (Avastin; a monoclonal antibody against VEGF) in adjuvant settings. We therefore explored whether a more complete blockade of VEGF signaling would be an effective strategy for cancer control by knocking down KDR expression in chemoresistant OVCAR-3 EOC cells using siRNA. Cells with KDR knockdown demonstrated more aggressive subcutaneous growth in vivo. In addition, when cells lacking KDR were implanted into the peritoneal cavity of immune deficient mice, these cells enhanced the accumulation of ascites characterized by higher VEGF levels. The cells lacking KDR showed increased Neuropilin-1 expression and decreased expression of some adhesion proteins, notable cadherins and integrins. Evaluation of 80 clinical cases of EOC for NRP-1 versus KDR expression showed a significantly higher NRP-1:KDR ratio with cancer progression. Our findings reveal additional complexity of interaction between VEGF pathway molecules in ovarian cancer, and demonstrate the potential limitations of applying specific molecular techniques in a therapeutic setting.  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 4284.
Prevalence of abdominal cystic echinococcosis in rural Bulgaria, Romania, and Turkey: a cross-sectional, ultrasound-based, population study from the HERACLES project
Authors: Francesca Tamarozzi, Okan Akhan, Carmen Michaela Cretu, Kamenna Vutova, Devrim Akinci, Rossitza Chipeva, Turkmen Ciftci, Corina Manuela Constantin, Massimo Fabiani, Branimir Golemanov, Denisa Janta, Patricia Mihailescu, Marin Muhtarov, Serra Orsten, Marius Petrutescu, Patrizio Pezzotti, Alexandru Cosmin Popa, Loredana Gabriela Popa, Mircea Ioan Popa, Valeri Velev, Mar Siles-Lucas, Enrico Brunetti, Adriano Casulli
Journal: The Lancet Infectious Diseases (2018)
Immunotherapy in CNS cancers: the role of immune cell trafficking
Authors: Nivedita M Ratnam, Mark R Gilbert, Amber J Giles
Journal: Neuro-Oncology (2018)

Glioblastoma (GBM) is a highly malignant CNS tumor with very poor survival despite intervention with conventional therapeutic strategies. Although the CNS is separated from the immune system by the blood–brain barrier (BBB) and the blood–cerebrospinal fluid barrier, emerging evidence of immune surveillance and the selective infiltration of GBMs by immune suppressive cells indicates that there is breakdown or compromise of these physical barriers. This in turn offers hope that immunotherapy can be applied to specifically target and reduce tumor burden. One of the major setbacks in translating immunotherapy strategies is the hostile microenvironment of the tumor that inhibits trafficking of effector immune cells such as cytotoxic T lymphocytes into the CNS. Incorporating important findings from autoimmune disorders such as multiple sclerosis to understand and thereby enhance cytotoxic lymphocyte infiltration into GBM could augment immunotherapy strategies to treat this disease. However, although these therapies are designed to evoke a potent immune response, limited space in the brain and cranial vault reduces tolerance for immune therapy–induced inflammation and resultant brain edema. Therefore, successful immunotherapy requires that a delicate balance be maintained between activating and retaining lasting antitumor immunity.
Glycosylation of Recombinant Anticancer Therapeutics in Different Expression Systems with Emerging Technologies
Authors: Tariq Nadeem, Mohsin Ahmad Khan, Bushra Ijaz, Nadeem Ahmed, Zia ur Rahman, Muhammad Shahzad Latif, Qurban Ali, Muhammad Adeel Rana
Journal: Cancer Research (2018)

Glycosylation, a posttranslational modification, has a major role in recombinant anticancer therapeutic proteins, as most of the approved recombinant therapeutics are glycoproteins. The constant amino acid sequence of therapeutics determines the enzymatic activity, while the presence of glycans influences their pharmacokinetics, solubility, distribution, serum half-life, effector function, and binding to receptors. Glycoproteins expressed in different expression systems acquire their own oligosaccharides, which increases the protein diversity. The heterogeneity of glycans creates hurdles in downstream processing, ultimately leading to variable anticancer therapeutic efficacy. Therefore, glycoproteins require an appropriate expression system to obtain structurally and functionally identical glycans, as in humans. In many expression systems, the N-glycosylation pathway remains conserved in the endoplasmic reticulum, but divergence is observed when the protein enters the Golgi complex. Hence, in recent decades, numerous approaches have been adopted to engineer the Golgi's N-glycosylation pathway to attain human-like glycans. Several researchers have tried to engineer the N-glycosylation pathway of expression systems. In this review, we examine the glycosylation pattern in various expression systems, along with emerging technologies for glycosylation engineering of anticancer therapeutic drugs. Cancer Res; 78(11); 2787-98. ©2018 AACR.
Temperature-controlled, phase-transition ultrasound imaging-guided photothermal-chemotherapy triggered by NIR light
Authors: Wei Li, Wanqing Hou, Xiaomeng Guo, Lihua Luo, Qingpo Li, Chunqi Zhu, Jie Yang, Jiang Zhu, Yongzhong Du, Jian You
Journal: Theranostics (2018)

Recently, nano-sized ultrasound contrast agents encapsulating drugs for cancer diagnosis and therapy have attracted much attention. However, the ultrasound signal of these agents is too weak to obtain an ideal ultrasound imaging effect. Furthermore, conventional ultrasound contrast agents with strong echo signal are not suitable for drug delivery against cancer because of their large size. To circumvent this problem, phase-transition ultrasound contrast agents are believed to be an excellent choice. Methods: Liposomes co-encapsulating doxorubicin (DOX), hollow gold nanospheres (HAuNS), and perfluorocarbon (PFC) were synthesized by film dispersion method. The morphology, particle size, and stability of these liposomes (DHPL) were investigated. The photothermal effect, drug release, particle size change, cytotoxicity, and ultrasound imaging were studied by using the near infrared (NIR) light. Furthermore, tumor accumulation of DHPL was observed by in vivo fluorescence imaging and the antitumor effect was verified in a 4T1 tumor model. Results: The nanosystem displayed a homogeneous size distribution (~200 nm) and an efficient light-to-heat conversion effect under 808 nm NIR laser irradiation. The nanometer size enabled considerable accumulation of DHPL in the tumor sites. The localized hyperthermia resulting from the photothermal effect of HAuNS could trigger the size transformation of DHPL followed by significant DOX release. Due to the gasification of PFC, a remarkably enhanced ultrasound signal was detected. DHPL also exhibited a prominent photothermally reinforced chemotherapeutic effect under the control of NIR light both in vitro and in vivo. Importantly, no systemic toxicity was observed by DHPL treatment. Conclusion: In this study, we fabricated multi-functional perfluorocarbon liposomes for ultrasound imaging-guided photothermal chemotherapy which have the potential to serve as a prospective cancer treatment approach.
Drug Slows Disability Progression in Multiple Sclerosis
Authors: Anita Slomski
Journal: JAMA (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
A Young Man With Cardiomegaly and Edema
Authors: Sushan Yang, Jared O’Leary, Mark A. Lawson
Journal: JAMA Cardiology (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Cardiology journal
Re: Niven Mehra, David Dolling, Semini Sumanasuriya, et al. Plasma Cell-free DNA Concentration and Outcomes from Taxane Therapy in Metastatic Castration-resistant Prostate Cancer from Two Phase III Trials (FIRSTANA and PROSELICA). Eur Urol 2018;74:283–91
Authors: Vincenza Conteduca, Giorgia Gurioli, Ugo De Giorgi
Journal: European Urology (2018)
Abstract B52: Brusatol inhibits oral squamous cell carcinoma cells by targeting glycolytic metabolism
Authors: Guilian Zhang, Ying Su, Suhong Chen, Xinyan Zhang
Journal: Cancer Research (2018)

Abstract Brusatol is a natural terpenoid that is isolated from the Brucea javanica plant, a medicine plant distributed widely throughout Asia, and its bitter fruits have been used traditionally in medicine for treating various ailments and controlling some pests. Brusatol has recently been shown to be capable of inducing a variety of biologic effects, including a potential antitumor effect. The goal of this study was to investigate the role of brusatol in oral squamous cell carcinoma (OSCC) cells and its mechanism. Brusatol treatment had broad effects against oral cancer cells in vitro including inhibition of proliferation, colony formation, cell migration and invasion, and induction of apoptosis. Mechanism studies showed that brusatol inhibited glucose uptake and lactate secretion and glycolytic pathway key enzymes HK and PK activity in vitro. Brusatol inhibited glycolysis, glycolytic capacity, and reserve capacity by Seahorse XF glycolysis stress test assay. In vivo study showed that brusatol suppresses tumor growth in a nude mouse xenograft model by inhibiting cell proliferation and angiogenesis and by inducing apoptosis. Glycolysis-related genes were also deceased in the nude mice xenografts. Taken together, these data clearly indicated that brusatol is a promising chemotherapeutic agent for OSCC treatment. Citation Format: Guilian Zhang, Ying Su, Suhong Chen, Xinyan Zhang. Brusatol inhibits oral squamous cell carcinoma cells by targeting glycolytic metabolism [abstract]. In: Proceedings of the AACR Special Conference: Advances in Modeling Cancer in Mice: Technology, Biology, and Beyond; 2017 Sep 24-27; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(10 Suppl):Abstract nr B52.
Translation: The Universal Structural Core of Life
Authors: Chad R Bernier, Anton S Petrov, Nicholas A Kovacs, Petar I Penev, Loren Dean Williams
Journal: Molecular Biology and Evolution (2018)

The Universal Gene Set of Life (UGSL) is common to genomes of all extant organisms. The UGSL is small, consisting of <100 genes, and is dominated by genes encoding the translation system. Here we extend the search for biological universality to three dimensions. We characterize and quantitate the universality of structure of macromolecules that are common to all of life. We determine that around 90% of prokaryotic ribosomal RNA (rRNA) forms a common core, which is the structural and functional foundation of rRNAs of all cytoplasmic ribosomes. We have established a database, which we call the Sparse and Efficient Representation of the Extant Biology (the SEREB database). This database contains complete and cross-validated rRNA sequences of species chosen, as far as possible, to sparsely and efficiently sample all known phyla. Atomic-resolution structures of ribosomes provide data for structural comparison and validation of sequence-based models. We developed a similarity statistic called pairing adjusted sequence entropy, which characterizes paired nucleotides by their adherence to covariation and unpaired nucleotides by conventional conservation of identity. For canonically paired nucleotides the unit of structure is the nucleotide pair. For unpaired nucleotides, the unit of structure is the nucleotide. By quantitatively defining the common core of rRNA, we systematize the conservation and divergence of the translational system across the tree of life, and can begin to understand the unique evolutionary pressures that cause its universality. We explore the relationship between ribosomal size and diversity, geological time, and organismal complexity.