tbuckley/cabot-search huggingface dataset:
Letter by Verheyen et al Regarding Article, “Pacemaker Malfunction Attributed to Multidetector Cardiac Computed Tomography”
Authors: Nicolas Verheyen, Daniel Scherr, Martin Manninger
Journal: Circulation (2016)

We read with great interest the case report by Elagha and Weissman. 1 The authors reported on a pacemaker-dependent patient who underwent computed tomography (CT) coronary angiography with a 256-slice multidetector CT scanner.During direct exposure of the pacemaker to CT radiation, transient ventricular asystole was documented, and readout of device memory showed a sensed arrhythmia at a frequency similar to the CT gantry rotation speed.It is concluded that ionized radiation induced pacemaker dysfunction.The authors aim to raise awareness of this complication and recommend establishing routine safety procedures to prevent CT-induced pacemaker dysfunction, eg, asynchronous pacing.Their elegant report raises concerns about the safety of CT procedures for patients who have pacemakers, because they may induce electromagnetic interference.Their conclusions may lead to uncertainty among patients and healthcare providers.We therefore consider it important to put their conclusions into perspective with existing literature and questions that remain unanswered in the presented case.The authors correctly emphasize the vulnerability of pacemaker circuits to electromagnetic interference, but they make no mention of a potential involvement of the ventricular electrode.It is well known from previous magnetic resonance tomography studies, however, that pacemakers are distinctly more sensitive to magnetic flux density in unipolar than in bipolar sensing mode. 2 Among 245 patients with pacemakers (38% unipolar sensing) exposed to maximum 100-µT flux density, 3 of 4 pacemakers with induced dysfunction had electrodes programmed in unipolar sensing mode.Providing intracardiac electrogram readouts of the pacemaker should help in ruling out a potential involvement of the ventricular electrode.In this case, arrhythmia sensing should be more pronounced or only occur in the ventricular intracardiac electrogram.In a study by Hirose et al, 3 effects of CT radiation were tested in a series of pacemakers, and they found that pacemakers with the lowest sensing threshold were most sensitive to electromagnetic interference.We therefore kindly encourage the authors to provide intracardiac electrogram readouts, as well as data on sensing programming and minimal pacemaker sensing threshold to allow the readership a better contextualization of the described observation.Nevertheless, we are convinced that this case should raise awareness and lead to systematical studies investigating exact mechanisms and incidence of electromagnetic interference on pacemakers during multidetector CT scans.These should be carefully performed before proposing asynchronous stimulation in this setting, with a potential risk of inducing ventricular tachyarrhythmias.
235TiP Phase III study of short-term radiotherapy followed by neoadjuvant chemotherapy versus preoperative long-term chemoradiotherapy in locally advanced rectal cancer
Authors: Y. Tang, J. Jin, N. Ling, H. Ren, W.-H. Wang, Y.-W. Song, Y.-P. Liu, S.-L. Wang, H. Fang, Y.-X. Li
Journal: Annals of Oncology (2015)
Contribution of Deregulated miRNAs to the Phenotypic Characteristic of Hodgkin Lymphoma.
Authors: Lu Ping Tan, Bart-Jan Kroesen, Enrico Tiacci, Gerben Duns, Erwin Seinen, Ody Sibon, Klaas Kok, Sibrand Poppema, Anke Van Den Berg
Journal: Blood (2009)
Unexpected high incidence of hepatocellular carcinoma in patients with hepatitis C in the era of DAAs: Too alarming?
Authors: Qing-Lei Zeng, Zhi-Qin Li, Hong-Xia Liang, Guang-Hua Xu, Chun-Xia Li, Da-Wei Zhang, Wei Li, Chang-Yu Sun, Fu-Sheng Wang, Zu-Jiang Yu
Journal: Journal of Hepatology (2016)
Panayiotopoulos syndrome
Authors: M. Koutroumanidis
Journal: BMJ (2002)

Epilepsy affects 1% of the general population and 4% of children, encompassing heterogeneous seizure syndromes.1 These are defined by distinct aetiology, age at onset, seizure type, and electroencephalographic features, which taken together provide the key to diagnosis, prognosis, and optimal management. Over the past two decades various distinct paediatric epilepsy syndromes, such as rolandic epilepsy, have been formally recognised.2 Panayiotopoulos syndrome is a new idiopathic childhood epilepsy, recently recognised by the International League Against Epilepsy.2 3 It is common, benign, and may mimic other common illnesses.

Awareness of this syndrome is important for all professionals who care for children with epileptic seizures, including general practitioners and community nurses, paediatricians and paediatric neurologists and clinical neurophysiologists, for the following reasons. Firstly, it is common. It probably affects about 13% of children of 3-6 years old with one or more non-febrile seizures (peak age 4-5 years), and 6% of the age group 1-15.4 5 Secondly, seizures can be prolonged, may mimic non-epileptic disorders, and may vary in severity from trivial to apparently life threatening—implying that the diagnosis may need to be considered in a variety of clinical settings and by medical professionals of different specialties. Thirdly, it is benign—its recognition therefore can provide firm reassurance to families in situations that …
Abstract 4589: Perturbation of epidermal growth factor (EGF) receptor internalization by novel aspirin analogues in SW480 cells
Authors: Asma’U I.J. Bashir, Sarah Jones, Christopher J. Perry, Stephen T. Safrany, Iain D. Nicholl
Journal: Cancer Research (2016)

Abstract BACKGROUND Colorectal cancer (CRC) is a global phenomenon with over 135 million new cases and over 600,000 deaths worldwide annually. The EGFR regulates normal growth and differentiation of cells, however its dysregulation is the cause of a wide range of cancers, including CRC. Activation of the EGFR requires phosphorylation at specific sites, which then leads to the recruitment of proteins and ultimately its internalization. The use of low-dose aspirin as a preventative agent is a controversial topic, particularly as the mechanism of action is hotly disputed. We have previously determined that novel aspirin analogues dramatically reduce EGFR phosphorylation in SW480 CRC cells; these cells express neither COX-1 nor COX-2, the perceived target for aspirin-like compounds. We have seen these aspirin analogues to also perturb the internalization of this receptor. METHODS SW 480 CRC cells were cultured in Leibovitz's L-15 medium on glass slides and starved for 48 hours. The cells were then treated with 0.5 mM aspirin analogues (ortho-aspirin, meta-aspirin, para-aspirin, ortho-thioaspirin, meta-thioaspirin and para-thioaspirin) for 30 minutes and then treated with EGF-tagged with AlexaFluor 555 for an hour. The reaction was the quenched with cold PBS, fixed and mounted on microscope slides with VectaShield + DAPI. Confocal microscopy was used to study the effect of these aspirin analogues on EGFR internalization. RESULTS EGF increased phosphorylation at all sites tested. We have peviously shown that these effects were prevented by preincubation with thioaspirins more potently than with aspirin and its positional isomers. These novel thioaspirins are also more potent in inhibiting proliferation of SW480 CRC cells. We now show these analogues prevent the internalization of EGFR. Instead they permit the formation of clusters. Aspirin and its analogues can perturb EGFR internalization and signalling in SW 480 cells. CONCLUSION The EGFR signalling pathway is a target for aspirin and aspirin analogues. The inhibition of receptor phosphorylation is accompanied by the loss of receptor internalization. Citation Format: Asma’U I.J. Bashir, Sarah Jones, Christopher J. Perry, Stephen T. Safrany, Iain D. Nicholl. Perturbation of epidermal growth factor (EGF) receptor internalization by novel aspirin analogues in SW480 cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4589.
Re-introduction of taxane for patients with esophageal squamous cell carcinoma refractory to 5-FU, CDDP, and a taxane
Authors: Takahiro Tsushima, Nomura Motoo, Satoru Iwasa, Ken Kato, Hirofumi Yasui, Kei Muro, Narikazu Boku
Journal: Annals of Oncology (2015)
A phase II trial of radiation and cetuximab followed by irinotecan/cetuximab for children with newly diagnosed diffuse pontine tumors and high-grade astrocytomas.
Authors: Margaret Macy, Mark W. Kieran, Susan N. Chi, Kenneth J. Cohen, Tobey MacDonald, Amy A. Smith, Michael Matthew Etzl, Aru Narendran, Lia Gore, Jennifer DiRenzo, Tanya M. Trippett, Nicholas K. Foreman, Ira J. Dunkel
Journal: Journal of Clinical Oncology (2013)

10030 Background: Diffuse intrinsic pontine gliomas (DIPG) and high-grade astrocytomas (HGA) have dismal prognoses. We previously demonstrated in a phase 1 study that cetuximab and irinotecan was a safe and tolerable regimen. Consequently, we initiated this 2-strata phase 2 trial to investigate the safety and efficacy of weekly cetuximab given with involved field external beam radiation therapy followed by 10 cycles of cetuximab and irinotecan for DIPG and HGA as determined by the 1-year progression-free survival. Methods: Eligible patients aged 3-21 years with newly diagnosed HGA or DIPG were enrolled to parallel strata. All patients received radiation therapy (5940 cGy) with concurrent cetuximab at 250mg/m 2 IV weekly for 6 weeks. Following radiation, patients received cetuximab (250mg/m 2 IV) weekly and irinotecan (16mg/m 2 /day IV) daily x 5 for two weeks every 21 days for 30 weeks. Tumor, serum, and CSF samples were collected for correlative studies. Sera collected at the onset of rash were analyzed for inflammatory and immune-related cytokines. Results: Forty-eight patients (27 DIPG, 21 HGA) were enrolled and 45 were treated (median age 8 years; range: 3–19). Toxicities were manageable; the most common adverse events were fatigue, gastrointestinal complaints, neutropenia, rash, headache, electrolyte abnormalities, elevated ALT/AST, and fever. Grade 3-4 events in ≥10% of patients were hypokalemia and lymphopenia. 4 patients experienced cetuximab-related hypersensitivity reactions (2 grade 3 reactions). The median PFS was 9.5 months (95% CI: 7.0-12.2) for HGA and 7.8 months (7.0-8.6) for DIPG with a 1-year PFS±SE of 24±10% and 25%±10% respectively. The median OS for HGA was 17.7 months (95% CI: 14.1-18.0) and 11.5 months (8.8-14.2) for DIPG. Biological correlative studies will be presented. Conclusions: Cetuximab and radiation therapy followed by cetuximab and irinotecan is well tolerated in children. Based on the 1-year PFS, this regimen may deserve further investigation in patients with DIPG. Biological correlative studies will delineate the mechanisms of the rash and possible implications for EGFR-targeted therapeutics in such patients. Clinical trial information: NCT01012609.
Abstract 2358: KHK2805, a novel ADCC- and CDC-enhanced anti-FOLR1 antibody with AccretaMab® technology, shows a potent anti-tumor activity in combination with pemetrexed
Authors: Munetoshi Ando, Keiko Nagata, Toshihiko Ishii, Ryuichiro Nakai, Takeshi Takahashi
Journal: Cancer Research (2016)

Abstract Introduction: Folate receptor 1 (FOLR1, FR alpha) is a folate transporter which is expressed in many cancers including ovarian cancer (OvC) and non-small cell lung cancer (NSCLC), and which is an attractive target for cancer therapy, is currently the subject of ongoing studies. We established KHK2805, a novel anti-FOLR1 monoclonal antibody with AccretaMab® technology to enhance both the antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) activities. It was demonstrated that KHK2805 exhibits markedly high ADCC and CDC activity levels in clinical samples from ovarian cancer patients, while a tolerable safety profile has been observed in preclinical models using cynomolgus monkeys (100 mg/kg weekly for 4 weeks, intravenously). A greater understanding of the biology of FOLR1 is important for providing a novel therapeutic option for KHK2805 for patients with cancer. Pemetrexed (PEM), a second-generation anti-folate which inhibits thymidylate synthase, glycinamide ribonucleotide transformylase and dihydrofolate reductase, is used as a standard therapy for patients with cancers such as NSCLC. It is not fully understood how PEM treatment affects the expression of FOLR1 on cancer cells. We therefore examined the level of FOLR1 expression in cancer cells after PEM treatment, and the anti-tumor activity of KHK2805 in combination with PEM. Materials and Methods: The FOLR1 expression levels after PEM treatment were examined in OvC, NSCLC, and endometrial cancer cells by flow cytometry. The ADCC activity of KHK2805 against PEM-treated cells was evaluated. The anti-tumor activity of KHK2805 in combination with PEM was investigated in SCID mice. Results: Flow cytometry showed that PEM treatment increased the FOLR1 expression of various cancers such as OvC (IGROV1, SKOV3, MCAS), NSCLC (NCI-H1437, NCI-H2228), and endometrial cancer (MESSA, HEC1A, HEC1B) cells. In addition, PEM treatment enhanced the ADCC activity of KHK2805 against MCAS, NCI-H1437, and NCI-H2228, in comparison to cells that did not receive PEM treatment. Furthermore, the anti-tumor activity of KHK2805 in SCID mice bearing subcutaneous MCAS tumors was enhanced by PEM treatment. Conclusions: PEM induced further FOLR1 expression in OvC, NSCLC, and endometrial cancer, resulting in the enhancement of the ADCC activity of KHK2805. The use of KHK2805 with PEM might therefore be a potent therapeutic option. Citation Format: Munetoshi Ando, Keiko Nagata, Toshihiko Ishii, Ryuichiro Nakai, Takeshi Takahashi. KHK2805, a novel ADCC- and CDC-enhanced anti-FOLR1 antibody with AccretaMab® technology, shows a potent anti-tumor activity in combination with pemetrexed. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2358.
Abstract 1191: Anti-tumor effect of selective progesterone receptor modulator (ulipristal acetate) on endometrial cancer cell lines
Authors: Ha-Young Lee, A Ra Ko, Dong-Woo Kang, Yu-Seon Kim, Su-Min Kim, Tae-Wook Kang, Shin-Wha Lee, Yong-Man Kim
Journal: Cancer Research (2016)

Abstract Background: Endometrial cancer is the most common malignancy of the female reproductive tract and the third most common cause of death from women's cancer. Risk factors of endometrial cancer include high levels of estrogen, obesity, diabetes mellitus, breast cancer, long term use of tamoxifen, late menopause, high blood pressure, and increasing age. Although the exact mechanisms in endometrial carcinogenesis due to chronic exposure are unclear, it is though that the pro-proliferative and DNA-damaging effects of estrogen and its metabolites, related with and insufficient counterbalance by progesterone, promote the hyper-proliferation and transformation of cells. Selective progesterone receptor modulator (SPRM) is an agent that acts on the progesterone receptor. Ulipristal acetate (UA) is one of SPRM and other SPRM, such as Mifepristone, showed inhibitory effect on various endometrial cancer cell lines. UA has been available as an emergency contraception and a treatment for uterine leiomyoma. The effect of UA on leiomyoma is decreasing neovascularization, proliferation, and viability. Objective: This study was undertaken to investigate antitumor effect of UA and to explore the effect of combination treatment with chemotherapy drug in endometrial cancer. Method: Inhibitory concentration (IC), proliferation assay, and migration assay were performed using Ishikawa, HEC-1-A, HEC-1-B, and/or patient-derived primary cancer cells (PCC). Different concentration of UA were treated in endometrial cancer cell lines and PCCs for the each assay. The CellTiter-Glo assay were performed to investigate IC50 in cell lines and PCCs. Crystal violet staining and wound healing assay were performed to examine cell proliferation and migration. Results: UA inhibited cell viability of endometrial cancer cell lines and PCCs at high concentration, most abviously 10uM in dose-dependent manner. In combination treatment assay with paclitaxel, UA showed synergistic anti-tumor effect with low-dose of paclitaxel on cell lines and PCCs. Conclusions: We showed that combination treatment of UA and paclitaxel effectively than single treatment by low dosage. In summary, we are actively exploring new effective applicable drugs for endometrial cancer, and our data suggest that UA may have therapeutic value with chemo-combination treatment of patients with endometrial cancer. Citation Format: Ha-Young Lee, A Ra Ko, Dong-Woo Kang, Yu-Seon Kim, Su-Min Kim, Tae-Wook Kang, Shin-Wha Lee, Yong-Man Kim. Anti-tumor effect of selective progesterone receptor modulator (ulipristal acetate) on endometrial cancer cell lines. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1191.
FOCUS4: A prospective molecularly stratified, adaptive multicenter program of randomized controlled trials for patients with colorectal cancer (CRC).
Authors: Kai-Keen Shiu, Tim Maughan, Richard H. Wilson, Richard A. Adams, Cheryl Pugh, Louise Brown, David Fisher, Harpreet Wasan, Gary William Middleton, William P. Steward, Richard S. Kaplan
Journal: Journal of Clinical Oncology (2013)

TPS3645 Background: Targeted therapies based on somatic gene mutations or activated pathways have inhibited progression of some cancers. However, although various targets are identifiable in CRC, KRAS mutation is currently the only validated predictive biomarker for selection of a targeted therapy. FOCUS4 is a rolling phase II-III trial for testing in a staged way both the utility of molecular stratification and the efficacy of novel agents in subpopulations of mCRC patients. It is also a trial of a new strategy for testing stratified approaches to therapy in any biologically complex tumour type using a Multi-Arm, Multi-Stage design. Methods: The study population consists of subjects with newly diagnosed inoperable mCRC. Subjects receive first-line chemotherapy for 16 weeks. During this time the tumour is tested for BRAF/PIK3CA/KRAS/NRAS mutations and PTEN loss. Subjects with responding or stable disease on CT, who would normally be candidates for a treatment break, are then randomised to four coherent biomarker-based subgroups: FOCUS4-A: BRAF mutant, FOCUS4-B: PIK3CA mutant or complete loss of PTEN on IHC, FOCUS4-C: KRAS or NRAS mutant, FOCUS4-D: All wild type (no mutations of BRAF, PIK3CA, KRAS or NRAS). For each subgroup, a relevant novel agent or combination is to be tested in an adaptive double-blind placebo controlled randomised trial design with multiple interim analyses for early termination if there is no strong evidence of worthwhile activity. There will also be a 5 th subgroup FOCUS4-N testing maintenance capecitabine for unclassifiable tumours or for patients whose marker defined cohort is temporarily suspended. The primary endpoint is progression free survival. Promising results in any biomarker defined cohort will then be tested for response in cohorts without the biomarker. Within the overall trial, biomarker developments can be accommodated with changes in the distribution of the cohorts or testing of new targeted agents. Enrolment will commence in May 2013. Upto 3400 patients will be registered over a 4-5 year period depending on which cohorts pass their staged interim analyses and proceed to later stages, including an overall survival endpoint. Clinical trial information: 2012-005111-12.
Inactivation of p53 and deletion of ATM in B-CLL patients inrelation to IgVH mutation
Authors: Martin Trbušek, Jitka Malčíková, Jana Šmardová, Viera Kuhrová, Dita Mentzlová, Soňa Bukovská, Petr Kuglík, Michael Doubek, Yvona Brychtová, Šárka Pospíšilová, Dana Dvořáková, Jiří Vorlíček, Jiří Mayer, Miluše Svitáková, Věra Linková, Jiří Začal, Jitka Kujíčková
Journal: Leukemia (2006)
Oestrogen-containing contraceptive pills increase vitamin D levels, study finds
Authors: Susan Mayor
Journal: BMJ (2016)

Taking oestrogen-containing oral contraceptives is associated with increased vitamin D levels, a large US follow-up study has shown.1

Previous small studies have found that taking oestrogen in hormone replacement therapy or oral contraception may be associated with increases in serum levels of 25 hydroxyvitamin D (25[OH]D), which is the widely accepted clinical biomarker of vitamin D status. But it has been unclear whether this was a causative effect or due to other lifestyle factors.

Researchers investigated the …
Poor continuity of primary care may increase mortality in elderly people, study shows
Authors: Susan Mayor
Journal: BMJ (2016)

Poor continuity of care in general practice is associated with increased mortality in older adults, a 17 year follow-up study in the Netherlands has shown.1

Although continuity of care is a widely accepted core principle of high quality primary care, evidence of its benefits has been limited. Researchers followed up 1712 people aged over 60 who were taking part in the ongoing Longitudinal Aging Study Amsterdam, which includes a randomly selected sample of older adults.

Data on study …
T Cell Receptors Specific for the Intracellular Transcription Factor Bob1 Allow Efficient Targeting of Human B Cell Leukemia and Multiple Myeloma
Authors: Lorenz Jahn, Pleun Hombrink, Michel G.D. Kester, Dirk M. van der Steen, Renate S. Hagedoorn, Chopie Hassan, Marjolein P. Schoonakker, Erwin van der Pijl, Peter A. van Veelen, J.H. Frederik Falkenburg, Mirjam H.M. Heemskerk
Journal: Blood (2014)
Abstract 4979: Cabozantinib eradicates advanced murine prostate cancer by activating neutrophil-mediated anti-tumor innate immunity
Authors: Akash Patnaik, Kenneth D. Swanson, Eva Csizmadia, Marina P. Gehring, Katja Helenius, Athalia R. Pyzer, Lily C. Wang, Jesse Novak, Olivier Elemento, Thomas B. Thornley, John M. Asara, John G. Clohessy, Kathy Kelly, Pier Paolo Pandolfi, Jacalyn M. Rosenblatt, David E. Avigan, Huihui Ye, Sabina Signoretti, Steven P. Balk, Lewis C. Cantley
Journal: Cancer Research (2016)

Abstract Several kinase inhibitors targeting aberrant signaling pathways in tumor cells have been deployed in cancer therapy. However, their impact on the tumor immune microenvironment remains poorly understood. The tyrosine kinase inhibitor cabozantinib showed striking responses in cancer clinical trial patients across several malignancies. Here we show that cabozantinib rapidly eradicates invasive, poorly-differentiated PTEN/p53 deficient murine prostate cancer. This was associated with enhanced release of neutrophil chemotactic factors from tumor cells, including CXCL12 and HMGB1, resulting in robust infiltration of neutrophils into the tumor. Critically, cabozantinib-induced tumor clearance in mice was abolished by antibody-mediated granulocyte depletion or HMGB1 neutralization or blockade of neutrophil chemotaxis with the CXCR4 inhibitor, plerixafor. Collectively, these data demonstrate that cabozantinib triggers a neutrophil-mediated anti-tumor innate immune response, resulting in rapid tumor clearance. Citation Format: Akash Patnaik, Kenneth D. Swanson, Eva Csizmadia, Marina P. Gehring, Katja Helenius, Athalia R. Pyzer, Lily C. Wang, Jesse Novak, Olivier Elemento, Thomas B. Thornley, John M. Asara, John G. Clohessy, Kathy Kelly, Pier Paolo Pandolfi, Jacalyn M. Rosenblatt, David E. Avigan, Huihui Ye, Sabina Signoretti, Steven P. Balk, Lewis C. Cantley. Cabozantinib eradicates advanced murine prostate cancer by activating neutrophil-mediated anti-tumor innate immunity. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4979.