tbuckley/cabot-search huggingface dataset:
Abstract POSTER-BIOL-1322: Natural anti-glycan IgM recognize P1 glycosphingolipid expressed on ovarian cancer cells
Authors: Francis Jacob, Merrina Anugraham, Tatiana Pochechueva, Brian Wan-Chi Tse, Shahidul Alam, Rea Guertler, Nicolai V. Bovin, André Fedier, Neville F. Hacker, Margaret E. Huflejt, Nicolle Packer, Viola A. Heinzelmann-Schwarz
Journal: Clinical Cancer Research (2015)

Abstract Recent research strongly suggests a role of plasma-derived anti-P1 antibodies (AGA) in ovarian cancer, as demonstrated by three independent glycan-based immunoassays. The level of these antibodies was lower in ovarian cancer patients and therefore discriminate cancer patients from healthy women. Here we investigate in a separate Australian cohort (n=155) whether IgM or IgG to P1 accounts for this discrimination and whether plasma matched ascites samples contain AGA. We also aimed to identify the P1 antigen in cancer tissue and cultured cells that are recognized by naturally occurring anti-P1 IgM and to investigate the potential function in respect to cell migration. Our results demonstrated that the IgM to P1 discriminates patients with ovarian cancer from healthy controls (p=0.0002) and that lower anti-P1 antibody levels are associated with a slightly higher risk for early relapse. Mass spectrometry identified P1 and structurally related epitopes in fresh tissue specimens and cultured cells. Ovarian cancer cell line IGROV1 was identified to be P1-positive while others (n=7) including human ovarian surface epithelial cells were negative determined by comprehensive flow cytometry. Epitope-mapped and characterized affinity purified anti-P1 antibodies from ascites were shown to bind P1-expressing cancer cells. IGROV1 was cell-sorted into two subpopulations, P1–high (66.1%) and P1-low (33.3%) and we found a significantly higher migration rate in P1-high expressing cells. Plasma-and ascites-derived natural anti-P1 IgM bind to the corresponding selfantigen expressed on the ovarian cancer cell surface. These findings are in concordance with the literature on natural IgM as part of the innate immune system recognizing carbo-neo-epitopes. These results deliver the first evidence that P1 may also be involved in cell migration and therefore may have a role in metastasis. Citation Format: Francis Jacob, Merrina Anugraham, Tatiana Pochechueva, Brian Wan-Chi Tse, Shahidul Alam, Rea Guertler, Nicolai V. Bovin, André Fedier, Neville F. Hacker, Margaret E. Huflejt, Nicolle Packer, Viola A. Heinzelmann-Schwarz. Natural anti-glycan IgM recognize P1 glycosphingolipid expressed on ovarian cancer cells [abstract]. In: Proceedings of the 10th Biennial Ovarian Cancer Research Symposium; Sep 8-9, 2014; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(16 Suppl):Abstract nr POSTER-BIOL-1322.
Brief Communication: Possible Gene Complementation in In Vitro Cell Lines of Ehrlich Ascites Tumor Established by Cell Fusion With Sendai Virus2
Authors: Michihiro C. Yoshida, Kenji Funaki
Journal: JNCI Journal of the National Cancer Institute (1974)

Cells of the hyperdiploid Ehrlich ascites tumor were readily adapted to grow in vitro after cell fusion by Sendai virus. NQ cell growth occurred in untreated control cultures. The quinacrine fluorescent analysis of the karyotype revealed that the cultured cells were progeny of hybrids formed between 2 karyotypically different cells. Rapid and extensive chromosome loss occurred in the hybrid line within 30 days of culture, and the stemline chromosome number shifted trom the 25 to hyper-1s region. The results of karyotype analyses in the original hybrid line and its hyper-1s clones suggested that the in vitro growth potential of the hybrid cells was operated by possible Jene complementation between the parental karyotypes and that the chromosomes involved in this unique mechanism might not be numerous.
Differential clinical and prognostic impact of myeloid sarcoma vs medullary myeloid blast phase of chronic myelogenous leukemia in the era of tyrosine kinase inhibitor therapy
Authors: Z Chen, W Wang, J E Cortes, E Liu, R N Miranda, C Zhao, J Yuan, X Lu, W Yang, M D Ameri, H M Kantarjian, L J Medeiros, S Hu
Journal: Blood Cancer Journal (2016)

Myeloid sarcoma (MS) is a rare neoplasm consisting of immature myeloid cells that forms a tumor mass at an anatomic site other than the bone marrow (BM).1 MS may develop de novo or secondary to other types of myeloid neoplasm. MS is most often associated with acute myeloid leukemia (AML), and develops in 2–5% of AML patients.2, 3 Less frequently, MS can arise in patients with chronic myelogenous leukemia (CML), mainly in the setting of blast phase (BP) or accelerated phase (AP).3, 4, 5 Traditionally, MS is considered the equivalent of AML, and is one of diagnostic criteria for CML-BP, regardless of the blast count in the BM or peripheral blood. According to the 2008 World Health Organization criteria, CML-BP can be diagnosed when: (1) blasts are ⩾20% in the BM or peripheral blood (medullary BP); or (2) there is an extramedullary blast proliferation, in other words, MS.
Nuclear Export Inhibitor KPT-8602 Is Highly Active Against Leukemic Blasts and Leukemia-Initiating Cells in Patient-Derived Xenograft Models of AML
Authors: Julia Etchin, Alla Berezovskaya, Amy Saur Conway, Weihsu Claire Chen, Erkan Baloglu, Yosef Landesman, William Senapedis, Joel Ellis, Dilara McCauley, Richard M. Stone, Ilene Galinsky, Daniel J. DeAngelo, Michael Kauffman, Sharon Shacham, Jean C.Y. Wang, A. Thomas Look
Journal: Blood (2015)
RAINBOW: A global, phase 3, double-blind study of ramucirumab (RAM) plus paclitaxel (PTX) versus placebo (PL) plus PTX in the treatment of advanced gastric and gastroesophageal junction (GEJ) adenocarcinoma following disease progression on first-line platinum- and fluoropyrimidine-containing combination therapy—An age-group analysis.
Authors: Kei Muro, Gyorgy Bodoky, Alvydas Cesas, Yee Chao, Philip Clingan, Shuichi Hironaka, Yoshito Komatsu, Galina Petrova Kurteva, Oleg N. Lipatov, Tomohiro Nishina, Sang Cheul Oh, Atsushi Ohtsu, Yasuhiro Shimada, Naotoshi Sugimoto, Eric Van Cutsem, Roberto Carlesi, Kumari Chandrawansa, Hansjochen Wilke
Journal: Journal of Clinical Oncology (2015)

11 Background: RAM is a human IgG 1 monoclonal antibody VEGF-R2 antagonist. The RAINBOW trial demonstrated that RAM added to PTX significantly improved overall survival (OS), progression free survival (PFS), and objective response rates (ORR) in 2 nd -line gastric and GEJ adenocarcinoma patients (pts). Outcomes are reported by pts aged &lt;65 and ≥65 yrs. Methods: Pts with advanced gastric and GEJ adenocarcinoma after disease progression on platinum- and fluoropyrimidine-based chemotherapy were randomized 1:1 to receive RAM (8 mg/kg) or placebo (PL) on days 1 and 15 plus PTX 80 mg/m 2 IV on days 1, 8, and 15 of a 28-day cycle. Eligible pts had ECOG PS ≤ 1 and adequate organ function. OS was the primary endpoint. Secondary endpoints included PFS, ORR, and safety. Results: Baseline characteristics were generally well balanced. Outcomes are summarized in the Table. The incidence of Grade ≥3 adverse events (AEs) was higher in the RAM+PTX arms for both age groups and similar across age groups. Grade ≥3 AEs occurring in ≥10% of pts and at higher rate in the RAM+PTX arm, and febrile neutropenia are shown in the Table. Conclusions: RAM+PTX conferred similar improvements over PL+PTX for OS, PFS, and ORR in both age groups. Toxicity profiles were similar in both groups, although a relatively higher incidence of Grade ≥3 neutropenia and leukopenia in pts ≥65 years was noted. [Table: see text]
Effectiveness of and Financial Returns to Voluntary Medical Male Circumcision for HIV Prevention in South Africa: An Incremental Cost-Effectiveness Analysis
Authors: Markus Haacker, Nicole Fraser-Hurt, Marelize Gorgens
Journal: PLoS Medicine (2016)

Empirical studies and population-level policy simulations show the importance of voluntary medical male circumcision (VMMC) in generalized epidemics. This paper complements available scenario-based studies (projecting costs and outcomes over some policy period, typically spanning decades) by adopting an incremental approach-analyzing the expected consequences of circumcising one male individual with specific characteristics in a specific year. This approach yields more precise estimates of VMMC's cost-effectiveness and identifies the outcomes of current investments in VMMC (e.g., within a fiscal budget period) rather than of investments spread over the entire policy period.The model has three components. We adapted the ASSA2008 model, a demographic and epidemiological model of the HIV epidemic in South Africa, to analyze the impact of one VMMC on HIV incidence over time and across the population. A costing module tracked the costs of VMMC and the resulting financial savings owing to reduced HIV incidence over time. Then, we used several financial indicators to assess the cost-effectiveness of and financial return on investments in VMMC. One circumcision of a young man up to age 20 prevents on average over 0.2 HIV infections, but this effect declines steeply with age, e.g., to 0.08 by age 30. Net financial savings from one VMMC at age 20 are estimated at US$617 at a discount rate of 5% and are lower for circumcisions both at younger ages (because the savings occur later and are discounted more) and at older ages (because male circumcision becomes less effective). Investments in male circumcision carry a financial rate of return of up to 14.5% (for circumcisions at age 20). The cost of a male circumcision is refinanced fastest, after 13 y, for circumcisions at ages 20 to 25. Principal limitations of the analysis arise from the long time (decades) over which the effects of VMMC unfold-the results are therefore sensitive to the discount rate applied, and more generally to the future course of the epidemic and of HIV/AIDS-related policies pursued by the government.VMMC in South Africa is highly effective in reducing both HIV incidence and the financial costs of the HIV response. The return on investment is highest if males are circumcised between ages 20 and 25, but this return on investment declines steeply with age.
Immune Responses to Shope Fibroma Virus in Adult and Newborn Rabbits
Authors: A. C. Allison
Journal: JNCI Journal of the National Cancer Institute (1966)

In adult domestic rabbits inoculated with Shope fibroma virus, tumors began to regress about the 9th day. Well-defined, delayed-type hypersensitivity reactions following intradermal challenge with virus antigen developed on the 5th day, but circulating antibody was not demonstrable before the 7th day. Second injections of virus produced tumors up to the 4th day but not later. Rabbits inoculated with virus shortly after birth had progressively growing tumors. Circulating antibody was demonstrable in the newborns on the 7th or 8th day, but no delayed-type reaction could be elicited, even by passive transfer of lymph node cells into the skins of adult rabbits carrying fibromas. From these results and experiments with immunosuppressants it is concluded that the main Factor involved in the regression of the fibroma is the cellular immune response, and that the failure of this response can account For the progressive growth of fibromas in newborns.
New Salvo Against Opioid Abuse
Authors: Rebecca Voelker
Journal: JAMA (2016)

Building on its recent efforts to reverse the US epidemic of opioid abuse, the FDA has issued draft guidance for the pharmaceutical industry to develop generic abuse-deterrent formulations of approved opioid medications.

Last year, the FDA provided the industry with final guidance on developing abuse-deterrent versions of brand-name opioids. “We recognize that abuse-deterrent technology is still evolving and is only 1 piece of a much broader strategy to combat the problem of opioid abuse,” FDA Commissioner Robert Califf, MD, said in a statement (http://1.usa.gov/25nA0QN).
Over-the-scope clip-assisted endoscopic full-thickness resection after incomplete resection of rectal adenocarcinoma
Authors: Pavlos Lagoussis, Paola Soriani, Gian Tontini, Helmut Neumann, Luca Pastorelli, Germana de Nucci, Maurizio Vecchi
Journal: Endoscopy (2016)

Endoscopic resection is a valuable therapeutic option for early colorectal cancer (CRC), especially in high risk surgical patients [1]. A novel endoscopic full-thickness resection device (FTRD; Ovesco Endoscopy, Tübingen, Germany) has been developed recently to achieve complete endoscopic resection of early CRC [2] [3].
Cultural Influences Reflected in Divergent US vs UK Human Embryo Research Policies
Authors: Eli Y. Adashi
Journal: JAMA (2016)

In a first, the Human Fertilisation and Embryology Authority (HFEA) of the United Kingdom recently approved a research application to use a gene-editing tool on early human embryos (http://nyti.ms/219K7DR). The applicant, Kathy K. Niakan, PhD, a developmental biologist with the Francis Crick Institute in London, England, is seeking to define the molecular program of the earliest stages of human development.

The studies would use surplus embryos from in vitro fertilization treatments donated by consenting parties and would conclude at the embryonic blastocyst stage without transfer to a recipient uterus. Preliminary experiments to edit out select genes with an eye toward delineating their role in cell lineage fate specification—how the single cell of an embryo develops into different cell lines—may soon be under way.
Safety profiles of anti-CTLA-4 and anti-PD-1 antibodies alone and in combination
Authors: Celine Boutros, Ahmad Tarhini, Emilie Routier, Olivier Lambotte, Francois Leroy Ladurie, Franck Carbonnel, Hassane Izzeddine, Aurelien Marabelle, Stephane Champiat, Armandine Berdelou, Emilie Lanoy, Matthieu Texier, Cristina Libenciuc, Alexander M. M. Eggermont, Jean-Charles Soria, Christine Mateus, Caroline Robert
Journal: Nature Reviews Clinical Oncology (2016)
Endothelial Actions of ANP Enhance Myocardial Inflammatory Infiltration in the Early Phase After Acute Infarction
Authors: Wen Chen, Annett Spitzl, Denise Mathes, Viacheslav O. Nikolaev, Franziska Werner, Johannes Weirather, Katarina Špiranec, Katharina Röck, Jens W. Fischer, Ulrike Kämmerer, David Stegner, Hideo A. Baba, Ulrich Hofmann, Stefan Frantz, Michaela Kuhn
Journal: Circulation Research (2016)

Rationale: In patients after acute myocardial infarction (AMI), the initial extent of necrosis and inflammation determine clinical outcome. One early event in AMI is the increased cardiac expression of atrial natriuretic peptide (NP) and B-type NP, with their plasma levels correlating with severity of ischemia. It was shown that NPs, via their cGMP-forming guanylyl cyclase-A (GC-A) receptor and cGMP-dependent kinase I (cGKI), strengthen systemic endothelial barrier properties in acute inflammation. Objective: We studied whether endothelial actions of local NPs modulate myocardial injury and early inflammation after AMI. Methods and Results: Necrosis and inflammation after experimental AMI were compared between control mice and littermates with endothelial-restricted inactivation of GC-A (knockout mice with endothelial GC-A deletion) or cGKI (knockout mice with endothelial cGKI deletion). Unexpectedly, myocardial infarct size and neutrophil infiltration/activity 2 days after AMI were attenuated in knockout mice with endothelial GC-A deletion and unaltered in knockout mice with endothelial cGKI deletion. Molecular studies revealed that hypoxia and tumor necrosis factor-α, conditions accompanying AMI, reduce the endothelial expression of cGKI and enhance cGMP-stimulated phosphodiesterase 2A (PDE2A) levels. Real-time cAMP measurements in endothelial microdomains using a novel fluorescence resonance energy transfer biosensor revealed that PDE2 mediates NP/cGMP-driven decreases of submembrane cAMP levels. Finally, intravital microscopy studies of the mouse cremaster microcirculation showed that tumor necrosis factor-α–induced endothelial NP/GC-A/cGMP/PDE2 signaling impairs endothelial barrier functions. Conclusions: Hypoxia and cytokines, such as tumor necrosis factor-α, modify the endothelial postreceptor signaling pathways of NPs, with downregulation of cGKI, induction of PDE2A, and altered cGMP/cAMP cross talk. Increased expression of PDE2 can mediate hyperpermeability effects of paracrine endothelial NP/GC-A/cGMP signaling and facilitate neutrophil extravasation during the early phase after MI.
Multiplex bead-based measurement of humoral immune responses against tumor-associated antigens in stage II melanoma patients of the EORTC 18961 trial
Authors: J. Michels, N. Becker, I. Kaiser, A. Benner, S. Agoussi, S. Suciu, N. Halama, D. Jäger, A.M.M. Eggermont, I. Zörnig
Journal: Annals of Oncology (2015)
Barefoot doctor
Authors: Trisha Greenhalgh
Journal: BMJ (2007)

Nothing is more flattering to the precious academic ego than being asked to be the subject of someone's dissertation. I have had walk-on parts in several MSc theses—chiefly in the role of (assumed) “opinion leader” in some topic or other, and an enlightened PhD student from the Netherlands once gave me a star part in her study of female role models in medicine.

Here's the latest request. My brother in law, an enthusiastic gardener with retirement looming, has signed up for a distance learning course on horticultural design. His thesis must describe the makeover of a garden along a theme of the candidate's choice. My garden (our garden, reminds spouse, who keeps the weeds at bay) has been selected from a short list of a dozen on the sole criterion of “room for improvement.” The theme, announced the brother in law, will be medicinal plants that will help me in my practice.

He came round for tea, armed with a pair of jumbo-sized tape measures, his soil analysis kit, and some grandiose ideas. The dampest and dingiest corner could be devoted to cardiology (“perfect climate for digitalis”). Over here, perhaps, the respiratory section (sage, garden myrrh). A raised bed against the back fence (to be built when we've uprooted the prickly bush that serves as the left half of the rugby goal) could be the dermatology department—lemon balm, camomile. And we'd need some neurological cures over here in the sun: nettles (really?), feverfew, angelica.

Quaint, isn't it? Every morning, before setting off to the surgery, I would refill my set of little brown bottles with fresh, scented leaves. Instead of worrying whether a borderline cholesterol level justifies an expensive statin, I could offer garlic, one clove t.d.s. Who needs topical non-steroidal anti-inflammatory drugs when I can formulate Tincture of Arnica in my trusty pestle and mortar? And all those stamped addressed envelopes from sedentary old people requesting “something for constipation” could be filled with a generous handful of senna pods.

I hate to admit it, but the project has got me thinking seriously about home grown remedies. Has anyone ever done a randomised controlled trial of Gaviscon versus peppermint tea for non-specific dyspepsia, or dock leaves versus chlorpheniramine for hives? Someone has certainly shown significant benefit over placebo for St John's wort in depression, and for ginger in hyperemesis gravidarum—and that was without the additional therapeutic benefit of nurturing the plant.

We're talking early days here. The thesis is yet to be written, and the kids are protesting against anything that might “stink.” But maybe, just maybe, I'll junk the British National Formulary and go barefoot for a while.
Microautoradiographic Localization of Bound Metabolites in the Nasal Cavities of F344 Rats Treated With the Tobacco-Specific Carcinogen 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: H Tjälve, A Castonguay, A Rivenson
Journal: JNCI Journal of the National Cancer Institute (1985)

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), the tobacco-specific N-nitrosamine, labeled with 14C on the carbonyl group, was given iv or orally to F334 rats. The animals were killed 4 hours later, and the localization of bound radioactivity in the nasal cavities was studied by light microscopic autoradiography. The strongest labeling was observed in the following groups of glands situated in the lamina propria mucosae: 1) Bowman's glands in the olfactory region, 2) the group of serous glands situated in the anterior half of the nasal septum beneath the respiratory epithelium, 3) the group of serous glands in the middle portion of the lateral wall of the nasal cavity, and 4) the lateral nasal gland (Steno's gland) located lateroventrally to the maxillary sinus. The group of mucous glands in the septum in connection with Jacobson's organ and the group of glands in connection with the dorsal, medial, and lateral parts of the maxillary sinus were not labeled. The olfactory and respiratory surface epithelia in the various parts of the nasal cavity were only weakly labeled. These results indicate that Bowman's glands, some serous glands, and Steno's glands are the principal sites where NNK is activated to alkylating species.
Host immune responses to antigens derived from a predominant strain of Mycobacterium tuberculosis
Authors: Yun-Gyoung Hur, Wou Young Chung, Ahreum Kim, Young Sun Kim, Hyon-Suk Kim, Sun-Hee Jang, Yeun Kim, Hyeyoung Lee, Kwang Joo Park, Sang-Nae Cho
Journal: Journal of Infection (2016)
Case 5-1967
Authors: Richard A. Field, Benjamin Castleman
Journal: New England Journal of Medicine (1967)

Presentation of Case First admission. A seventy-year-old man was admitted to the hospital because of abdominal pain.He had been well until a year previously, when he began to experience nonradiating periumbilical pain one to two hours after meals. The pain, which was most severe after a large meal but seemed unrelated to any type of food, was not relieved by antacids and was unaffected by activity. There was no history of pain in the chest, jaundice or melena. His weight was stable, and his appetite remained good.Physical examination revealed a man who appeared healthy. The optic fundi . . .
Spotlight on Volasertib: Preclinical and Clinical Evaluation of a Promising Plk1 Inhibitor
Authors: J. Van den Bossche, F. Lardon, V. Deschoolmeester, I. De Pauw, J.B. Vermorken, P. Specenier, P. Pauwels, M. Peeters, A. Wouters
Journal: Medicinal Research Reviews (2016)

Considering the important side effects of conventional microtubule targeting agents, more and more research focuses on regulatory proteins for the development of mitosis-specific agents. Polo-like kinase 1 (Plk1), a master regulator of several cell cycle events, has arisen as an intriguing target in this research field. The observed overexpression of Plk1 in a broad range of human malignancies has given rise to the development of several potent and specific small molecule inhibitors targeting the kinase. In this review, we focus on volasertib (BI6727), the lead agent in category of Plk1 inhibitors at the moment. Numerous preclinical experiments have demonstrated that BI6727 is highly active across a variety of carcinoma cell lines, and the inhibitor has been reported to induce tumor regression in several xenograft models. Moreover, volasertib has shown clinical efficacy in multiple tumor types. As a result, Food and Drug Administration (FDA) has recently awarded volasertib the Breakthrough Therapy status after significant benefit was observed in acute myeloid leukemia (AML) patients treated with the Plk1 inhibitor. Here, we discuss both preclinical and clinical data available for volasertib administered as monotherapy or in combination with other anticancer therapies in a broad range of tumor types.