tbuckley/cabot-search huggingface dataset:
Treatment of non-small cell lung cancer (NSCLC) patients with the trifunctional antibody catumaxomab (anti-EpCAM x anti-CD3): Results of a phase I/II study
Authors: B. Passlick, A. Schmittel, H. Friccius-Quecke, F. Kanniess, R. Wiewrodt, H. Lindhofer, M. Jaeger, M. Sebastian
Journal: Journal of Clinical Oncology (2006)

2540 Background: Catumaxomab is a trifunctional monoclonal antibody with binding specificities to human EpCAM, human CD3 and Fc gamma receptor I/III-positive accessory cells leading to induction of cell mediated, tumor specific cytotoxicity. As EpCAM is overexpressed in NSCLC patients (pts.) the present study was conducted in order to evaluate safety and tolerability of intravenous (i.v.) treatment with catumaxomab. Methods: Patients with NSCLC (UICC stage IB - IV) with at least one prior therapy were included into this trial. Escalating doses of 2–7,5 μg catumaxomab were given as a single i.v. infusion. Various doses of dexamethasone premedication (10 and 40 mg) were investigated at five different dose levels (level: catumaxomab (μg)/dexamethasone (mg)/number of pts. treated: I: 2/40/3, II: 2/0/1, III: 5/40/4, IV: 5/10/5, V: 7,5/40/2, respectively). Primary objectives were toxicity and definition of the maximum tolerated dose (MTD). In addition, time to progression (TTP) and survival were evaluated. Results: 24 pts. were included into this trial; 15 pts. were evaluable for safety analysis, 13 pts. for follow up. 13/15 pts. experienced a total of 68 AEs, of which 55 were reported as drug related and 9 defined as critical AEs. The majority (77%) of AEs were mild (CTC grade 1 and 2), 19% were grade 3 and 4% grade 4. 73% of the AEs were elevation of liver enzymes (gamma-GT, AST and ALT). Other toxicities were increase of blood ALP, dizziness, lymphopenia and pyrexia. Dose limiting toxicity (DLT) was a transient grade 3 and 4 elevation of ALT, AST and gamma-GT, observed at dose levels IV and V. Maximum tolerated dose (MTD) was defined at dose level III. Remarkably, follow up data showed 4/4 pts. stage IIIB and 1/4 pts. stage IV still alive at 26–28 months after catumaxomab treatment. Conclusion: 5 μg of catumaxomab can safely be administered intravenously with 40 mg dexamethasone as premedication. Based on the current results we recommend this regimen as first dose in a future study consisting of multiple catumaxomab infusions in pts. with locally advanced NSCLC. [Table: see text]
RARE-04PRIMARY INTRAVENTRICULAR LEIOMYOMA IN AN IMMUNOCOMPETENT PATIENT: A CASE REPORT AND REVIEW OF THE LITERATURE
Authors: Juanita Garces, Edison Valle, Tyler Scullen, Mansour Mathkour, Franklin Berry, Roger Smith
Journal: Neuro-Oncology (2015)

INTRODUCTION: Primary intracranial leiomyoma is an extremely rare presentation of low-grade mesenchymal tumor characterized by a proliferation of smooth muscle cells. The lesions predominantly occur in immunocompromised patients in the setting of infection or transplant, and have never been reported to involve the ventricular system. In this report we describe a case of primary leiomyoma of the lateral ventricle in an immunocompetent patient. CASE REPORT: A 30-year-old male with no past medical history presented with complaints of several weeks of progressive diplopia and occipital headaches. Magnetic resonance imaging revealed a homogenously enhancing mass of the left lateral ventricle with associated cerebral edema. The patient underwent interhemispheric transcollosal craniotomy for resection of this intraventricular tumor. Histopathology and immunohistochemistry was consistent with leiomyoma. Genetic probing for Epstein-Barr virus was negative. Computed tomography of the chest and abdomen failed to uncover a primary tumor. The patient did well post-operatively, and was discharged 3 days following resection. At 2-year follow up, there continues to be no evidence of recurrence. CONCLUSION: To date and up to our knowledge, there are less than 25 reported cases of primary intracranial leiomyoma including our case, with less than 15 reports occurring in immunocompetent individuals. We believe this is the first report of this tumor type occurring within the ventricles. As such, leiomyoma should be considered as a rare etiology in the differential diagnosis of intraventricular lesions.
Abstract 19944: A PDE5A Gene Mutation Affecting Risk of Myocardial Infarction
Authors: Tan An Dang, Ingrid Braenne, Redouane Aherrahrou, Stephanie Tennstedt, Thorsten Kessler, Christian Hengstenberg, Jeanette Erdmann, Heribert Schunkert
Journal: Circulation (2014)

INTRODUCTION: Multiple frequent genetic variants were shown to affect myocardial infarction (MI) risk. Genetic causes for familial clustering of MI are less clear. We aimed to identify and characterize the molecular underpinnings of premature MI in a family with 9 affected individuals. METHODS AND RESULTS: Employing cosegregation analysis and exome sequencing we identified a mutation in the phosphodiesterase 5A ( PDE5A ) gene in all affected individuals (LOD score 3.16). It is located in an alternative promoter site of PDE5A and leads to a premature stop codon in one of the PDE5A isoforms (p.Lys7Ter). PDE5A encodes for three isoforms catalyzing cGMP, a second messenger mediating vasodilation and platelet passivation. Effects of the stop codon were investigated by western blot analysis after in vitro mutagenesis. Overexpression in HEK cells did not reveal a loss of transcript but the expression of a N-terminally truncated protein. Deeper analyses of translation initiation by deletion of possible transcription starts via in vitro mutagenesis uncovered a protein lacking 91 amino acids compared to the full-length isoform. Activity of the truncated PDE5A was measured using PDEGlo (Promega). Moreover, the effect of the variant on the alternative promoter site was analyzed by luciferase assays. Therefore, a 600 bp fragment containing either the mutated or WT allele was cloned into a pGL4.10 vector (Promega). Overexpression in HEK cells showed 40% increase of promoter activity with the mutated allele (p&lt;0.05). Similar results could be shown in other cell lines. CONCLUSION: We identified a mutation in the PDE5A gene associated with premature MI. While a gain of function of PDE5A makes sense from a pathophysiological stance, the particular variant seemed to result in a premature stop codon. However, we could demonstrate that the variant might lead to increased promoter activity and that the presumable stop codon does not result into a loss of transcript but rather a truncated, potentially more active PDE5A isoform. Along with our homology modeling results and x-ray crystallographic and biochemical studies of Wang et al. (2010), these data support the idea of overexpression of a truncated though functional PDE5A in mutation carriers, possibly resulting in a gain function.
Proteomic Profile Of CD34+ Cells From Chronic Myeloid Leukemia Patients and From Normal Donors
Authors: Maria Rosaria Ricciardi, Valentina Salvestrini, Mattia Forcato, Roberto Licchetta, Simone Mirabilii, Lara Rossi, Matteo Allegretti, Martina Vincenzi, Simona Salati, Fausto Castagnetti, Gianantonio Rosti, Giuliana Alimena, Rossella Manfredini, Silvio Bicciato, Roberto Lemoli, Agostino Tafuri
Journal: Blood (2013)
US health officials press Congress for Zika funds
Authors: Michael McCarthy
Journal: BMJ (2016)

Tom Frieden, director of the US Centers for Disease Control and Prevention, has called on Congress to move quickly to appropriate funds to support the government’s response to the Zika virus disease epidemic.

Frieden, who had returned from touring the US territory of Puerto Rico, where an outbreak of Zika infections was ongoing, told reporters that funding was “crucially important and urgently needed.” “The rains are coming, and with the rains will come mosquito season, and with mosquito season will be the risk of an explosive spread of …
Allogeneic Hematopoietic Cell Transplantation Is Effective In Patients With Advanced Systemic Mastocytosis: A Multicenter Retrospective Analysis
Authors: Celalettin Ustun, Andreas Reiter, Bart L Scott, Ryotaro Nakamura, Damaj Gandhi, Sebastian Kreil, Ryan Shanley, William J Hogan, Miguel-Angel Perales, Tsiporah B. Shore, Herrad Baurmann, Robert K Stuart, Bernd Gruhn, Michael Doubek, Jack W Hsu, Eleni Tholouli, Tanja Gromke, Lucy A Godley, Livio Pagano, Andrew Gilman, Eva Maria Wagner, Tor Shwayder, Martin Bornhaeuser, Esperanza B Papadopoulos, Alexandra Boehm, Gregory M Vercellotti, Maria Theresa Van Lint, Christoph Schmid, Werner Rabitsch, Vinod Pullarkat, A. John Barrett, Olivier Hermine, Hans Gustaf Hagglund, Wolfgang R Sperr, Uday R Popat, Steven M. Devine, H. Joachim Deeg, Daniel J. Weisdorf, Cem Akin, Peter Valent
Journal: Blood (2013)
Dysgerminoma of the ovary: Review of 32 cases
Authors: O. Streltsova, S. Tjulandin, K. Jordaniya, V. Kuznetsov, A. Kedrova
Journal: Journal of Clinical Oncology (2007)

16072 Purpose: This study was undertaken to determine the frequency, characteristics, treatment and outcome of patients with dysgerminomas in single institution between 1990 and 2006. Methods: A total of 32 patients with pure dysgerminoma were retrospectively reviewed, among whom 23 patients had primary treatment in NNBRCRC during the period 1990–2006 and referred for follow-up (n=1) or salvage therapy after recurrence (n=9). Results: The median (range) age at presentation was 21 (14–42) years. 17 women (53%) presented with FIGO surgical stage I disease, 2 (6%) had pelvic metastases (stage II), and 9 (28%) had advanced (stage III/IV) disease. 4 patients had no comprehensive surgical staging. 2 women had evidence of dysgenetic gonads with a 46 XY karyotype. Primary surgery was done in all patients. 22 patients (69%) underwent fertility-sparing surgery. 4 (13%) patients received no adjuvant treatment after surgery due to stage Ia. All of them are alive without evidence of disease at a median (range) follow-up of 4,2 (2–6,4) years. Postoperative systemic chemotherapy was administered to 28 (87%) women. 16 of them received adjuvant chemotherapy and 12 received chemotherapy for metastatic disease. Among them 20 received platinum-based chemotherapy. Six patients had disease progression during first-line systemic treatment, all women received non-platinum-based chemotherapy. Three of them were salvage with second-line cisplatinum-based chemotherapy. Two deaths were associated with progressive disease, and one patient died of intercurrent disease. Overall, 29 women (90%) are alive without evidence of disease at a median follow-up of 68 months. Conclusions: Our date confirmed that the majority of patients can be managed with fertility sparing surgery and platinum-based adjuvant treatment without compromising survival. No significant financial relationships to disclose.
Different regulation of cigarette smoke induced inflammation in upper versus lower airways: findings from a mouse model
Authors: Wouter Huvenne, Claudina Perez Novo, Natalie De Ruyck, Nele Pauwels, Lander Robays, Tania Maes, Paul Van Cauwenberge, Guy Joos, Guy Brusselle, Claus Bachert
Journal: Allergy (2009)
Shaken baby witness was dishonest about her expertise, finds tribunal
Authors: Clare Dyer
Journal: BMJ (2016)

A leading expert witness who gave evidence for parents in alleged “shaken baby” cases was dishonest in acting outside her expertise and in deliberately misrepresenting the research literature, a medical practitioners’ tribunal has ruled.

Waney Squier, a consultant neuropathologist since 1984, changed her opinion on the mechanisms of abusive head trauma after the publication of hypotheses by the clinical neuropathologist Jennian Geddes,1 said the tribunal chair, Michele Codd.

The tribunal found that, in Squier’s written and oral evidence to courts, she was “dogmatic, inflexible, and unreceptive to any other view” and that she “cherry picked” the literature to support her argument …
SIRT6 Overexpression Potentiates Apoptosis Evasion in Hepatocellular Carcinoma via BCL2-Associated X Protein–Dependent Apoptotic Pathway
Authors: Long-Kuan Ran, Yong Chen, Zhen-Zhen Zhang, Na-Na Tao, Ji-Hua Ren, Li Zhou, Hua Tang, Xiang Chen, Ke Chen, Wan-Yu Li, Ai-Long Huang, Juan Chen
Journal: Clinical Cancer Research (2016)

Abstract Purpose: To characterize the functional role of SIRT6 in hepatocellular carcinoma (HCC). Experimental Design: The expression of SIRT6 in 60 paired paraffin-embedded HCC tissues and adjacent nontumoral liver tissues was examined by immunohistochemistry. The expression of SIRT6 in 101 paired frozen HCC tissues and adjacent nontumoral liver tissues was analyzed by Western blotting analysis and qPCR. The biologic consequences of overexpression and knockdown of SIRT6 in HCC cell lines were studied in vitro and in vivo. Results: SIRT6 expression was frequently upregulated in clinical HCC samples, and its expression was highly associated with tumor grade (P = 0.02), tumor size (P = 0.02), vascular invasion (P = 0.004), and shorter survival (P = 0.024). Depletion of SIRT6 from multiple liver cancer cell lines inhibited their growth and induced apoptosis in vitro. At the molecular level, we observed that the activation of the BCL2-associated X protein (Bax) signaling pathway, a major pathway that determines cancer cell apoptosis, is regulated by SIRT6 via its deacetylase activity. SIRT6 was recruited to the promoter of Bax, where it deacetylated histone 3 lysine 9 and suppressed its promoter activity. Binding of transcription factors (p53 and E2F-1) to Bax promoter was also generally increased in SIRT6-depleted cells. In mouse xenografts, SIRT6 suppression inhibited tumor growth and induced apoptosis. Finally, there is a negative correlation between SIRT6 and Bax mRNA expressions in human HCC samples. Conclusions: SIRT6 is an important protumorigenic factor in liver carcinogenesis. Thus, the therapeutic targeting of SIRT6 may offer options for HCC treatment. Clin Cancer Res; 22(13); 3372–82. ©2016 AACR.
Differential Analysis of Cyclocytidine, 1-β-D-Arabinofuranosylcytosine, and 1-β-D-Arabinofuranosyluracil by Ultraviolet Spectophotometry2
Authors: R. L. Furner, R. W. Gaston, J. D. Strobel, S. El Dareer, L. B. Mellett
Journal: JNCI Journal of the National Cancer Institute (1974)

Journal Article Differential Analysis of Cyclocytidine, 1-β-D-Arabinofuranosylcytosine, and 1-β-D-Arabinofuranosyluracil by Ultraviolet Spectophotometry Get access R. L. Furner, R. L. Furner Search for other works by this author on: Oxford Academic PubMed Google Scholar R. W. Gaston, R. W. Gaston Search for other works by this author on: Oxford Academic PubMed Google Scholar J. D. Strobel, J. D. Strobel Search for other works by this author on: Oxford Academic PubMed Google Scholar S. El Dareer, S. El Dareer Search for other works by this author on: Oxford Academic PubMed Google Scholar L. B. Mellett L. B. Mellett Biochemical Pharmacology Division, Kettering-Meyer Laboratories, Southern Research Institute, 2000 9th Ave. S., Birmingham, Ala. 35205 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 52, Issue 5, May 1974, Pages 1521–1528, https://doi.org/10.1093/jnci/52.5.1521 Published: 01 May 1974 Article history Received: 17 October 1973 Accepted: 25 January 1974 Published: 01 May 1974
High Level Engraftment of NOD/SCID Mice by Primitive Normal and Leukemic Hematopoietic Cells From Patients With Chronic Myeloid Leukemia in Chronic Phase
Authors: J.C.Y. Wang, T. Lapidot, J.D. Cashman, M. Doedens, L. Addy, D.R. Sutherland, R. Nayar, P. Laraya, M. Minden, A. Keating, A.C. Eaves, C.J. Eaves, J.E. Dick
Journal: Blood (1998)
Author confused natural birth with normal birth
Authors: C. Essex
Journal: BMJ (1996)

EDITOR,—Ann Oakley rightly wants quality of care and consumer satisfaction in childbirth to increase1; an increase in these two variables should be our aim in all aspects of medicine. Whether Oakley is well placed to judge them in childbirth is another matter.

In her description of her daughter in law's labour the health of the baby and mother takes second place to her acerbic comments about obstetricians. It is unclear why she believes that obstetricians, whom she derisively refers to as …
An Ether-Sensitive Antigen Associated With Bovine Leukemia Virus Infection2
Authors: M. Onuma, C. Olson, L. E. Baumgartener, L. D. Pearson
Journal: JNCI Journal of the National Cancer Institute (1975)

An ether-sensitive antigen (es-Ag) associated with bovine leukemia virus infection was detected by immunodiffusion tests. This antigen was sensitive to ether, sodium periodate, and trypsin treatment. Based on column chromatography, eS-Ag was a larger molecule than that of ether-resistant antigen (gs-Ag). With infection, precipitating antibody against es-Ag developed earlier than the precipitating antibody against the gs-Ag.
New recruitment contract for health and care services regulator dismays lay experts
Authors: Caroline White
Journal: BMJ (2016)

The private company recently made responsible for recruiting most of the non-clinical experts who inspect health and social care services in England has upped its rates of pay after previously halving them.

The move follows protests and resignations from existing post holders who conduct inspections for the regulator, the Care Quality Commission (CQC). But all new applicants will still be paid less, the employment agency Remploy has confirmed. It won the three year contract to recruit “experts by experience,” in three of the four CQC regions in England from 1 February this year.

Remploy informed existing recruits in January that hourly pay would be £9.40 …
Results of a clinical phase I dose-escalation study of cytarabine in combination with fixed dose vinorelbine, paclitaxel, etoposide, and cisplatin (VTEPA) for the treatment of relapsed/refractory lymphoma
Authors: M. L. Arellano, S. Lonial, A. Langston, C. Flowers, T. Heffner, D. Hutcherson, E. Winton, E. Waller
Journal: Journal of Clinical Oncology (2005)

6691 Background:High dose chemotherapy and autologous transplant remains the goal for patients with chemo-responsive relapsed lymphoma. Microtubule agents (Paclitaxel and Vinorelbine) may synchronize cells in G2/M phase, improving anti-tumor effects of cycle-specific agents. We conducted a phase I dose- escalation study of Cytarabine (AC)with fixed dose Vinorelbine (V), Paclitaxel (T), Etoposide (E), and Cisplatin (P)for patients with relapsed/refractory lymphoma. Methods:Therapy: day1: T 175mg/m2+V 30mg/m2; days 2–5: P 20 mg/m2+E 100mg/m2. AC 2 gm/m2over 4 hours in 3 cohorts: A on day 5; B days 4–5; C days 3–5. G-CSF and prophylactic anti-biotics were started on day 6. Standard response criteria were used. Results: 16 patients (6 HD; 10 NHL) enrolled. 14/16 (88%) were refractory, 7 (44%) primary refractory. M:F 1:1 and median age 44 (25–64 yrs.). Median # of prior regimens was 2 (1–9). Toxicities are described in table 1. A median of 5 units PRBCs and 2 units of platelets were given. Infectious complications included neutropenic fever, sepsis, and fungal pneumonia. There was one treatment-related death on day 7 of the protocol. Other toxicities: electrolyte imbalance, mild renal insufficiency and transient LFT elevation. Response:0 CR, 27% PR, 33% stable disease, and 40% PD. 5 patients went on to transplantation (4 auto, 1 allo), and 5/7 patients mobilized with VTEPA were successfully collected. Median OS was 225 days (range 7–1119 days) with 7 patients alive at last follow up. DLT occurred in the 3rd cytarabine cohort. Conclusion: VTEPA is active in patients with refractory lymphoma, and results in PBSC mobilization. This response rate after 1 cycle of therapy is significant in this refractory cohort. The regimen containing 2 days of AC forms the basis for a current phase II trial for patients with relapsed/refractory lymphoma. No significant financial relationships to disclose.
Travel-Associated Zika Virus Disease Cases Among U.S. Residents — United States, January 2015–February 2016
Authors: Paige Armstrong, Morgan Hennessey, Monica Adams, Cara Cherry, Sophia Chiu, Alexia Harrist, Natalie Kwit, Lillianne Lewis, Dana Olzenak McGuire, Titilope Oduyebo, Kate Russell, Pamela Talley, Mary Tanner, Charnetta Williams
Journal: MMWR Morbidity and Mortality Weekly Report (2016)

Zika virus is an emerging mosquito-borne flavivirus. Recent outbreaks of Zika virus disease in the Pacific Islands and the Region of the Americas have identified new modes of transmission and clinical manifestations, including adverse pregnancy outcomes. However, data on the epidemiology and clinical findings of laboratory-confirmed Zika virus disease remain limited. During January 1, 2015-February 26, 2016, a total of 116 residents of 33 U.S. states and the District of Columbia had laboratory evidence of recent Zika virus infection based on testing performed at CDC. Cases include one congenital infection and 115 persons who reported recent travel to areas with active Zika virus transmission (n = 110) or sexual contact with such a traveler (n = 5). All 115 patients had clinical illness, with the most common signs and symptoms being rash (98%; n = 113), fever (82%; 94), and arthralgia (66%; 76). Health care providers should educate patients, particularly pregnant women, about the risks for, and measures to prevent, infection with Zika virus and other mosquito-borne viruses. Zika virus disease should be considered in patients with acute onset of fever, rash, arthralgia, or conjunctivitis, who traveled to areas with ongoing Zika virus transmission (http://www.cdc.gov/zika/geo/index.html) or who had unprotected sex with a person who traveled to one of those areas and developed compatible symptoms within 2 weeks of returning.
STEM-07EXPOSING GLIOBLASTOMA STEM CELLS TO LEVETIRACETAM RESULTS IN AN ALTERED MOLECULAR PROGRAM
Authors: Markus Luedi, Sanjay Singh, Eric Sulman, Frederick Lang, Rivka Colen, Pascal Zinn
Journal: Neuro-Oncology (2015)

Glioblastoma stem cells (GSCs) are widely accepted as key players in glioblastoma (GBM) pathogenesis. Levetiracetam is extensively used for both prevention and therapy of seizures in GBM and also reported to inhibit glioma cell proliferation. However, its global impact on expression profiles specifically in GSC is unknown. The purpose of this research was to evaluate the impact of Levetiracetam on the expression profiles and cellular properties of GSCs. Total RNA from two independent GSC lines after Levetiracetam exposure was used for mRNA and miRNA expression profiling by microarrays. Gene ontology (GO) and ingenuity pathway analyses (IPA) of differentially expressed genes including miRNAs were used to uncover altered pathways. Additionally, the impact of Levetiracetam on cellular properties such as self-renewal (limiting dilution assay), differentiation (neural lineage marker analysis), proliferation (BrdU labeling), and invasion (Boyden chamber assays) was studied. Exposure to Levetiracetam altered expression profiles of GSCs. Gene ontology (GO) and ingenuity pathway analyses (IPA) of significantly altered genes in Levetiracetam treated cells show multiple cellular functions being potentially affected. Further, in vitro experiments such as self-renewal, differentiation, proliferation and migration/invasion assays indeed showed a significant impact on cellular behavior upon treatment of GSCs with Levetiracetam. In this pre-clinical study we uncovered the impact of Levetiracetam on the expression profiles of GSC, which alters the behavior of GSCs. These molecular findings bare potential to significantly impact GBM patient care by optimizing the established therapy with Levetiracetam.