tbuckley/cabot-search huggingface dataset:
Exercise induced laryngeal obstruction (EILO) diagnosed with laryngoscopy during rest or during exercise
Authors: Hege Clemm, Maria Vollsæter, Magnus Hilland, Astrid Sandnes, Lorentz Sandvik, Thomas Halvorsen, John-Helge Heimdal, Ola Røksund
Journal: European Respiratory Journal (2014)

Introduction Exercise Induced Inspiratory Symptoms (EIIS) are often confused with those of exercise induced asthma. EIIS tend to be attributed to inappropriate adduction of the vocal cords (VCD); however, EILO involves supraglottic adduction in a majority. It has been argued that laryngoscopy during maximum voluntary ventilation (MVV) is a suitable diagnostic tool for EILO.

Aim s Study relationships between supraglottic laryngoscopic findings obtained at MVV maneuvers at rest and during continuous laryngoscopy exercise (CLE) test.

Method Patients with EIIS at our institution have been offered a CLE-test the last 15 years. Video recordings from the two last years were analyzed in a blinded fashion for supraglottic laryngeal adduction during MVV maneuvers and CLE-tests, using Maat-score1 (mild, moderate, severe).

Results CLE-test recordings from 198 patients were analyzed, 177 were technically adequate and 106 were considered positive with a moderate or severe supraglottic adduction. MVV at rest resulted in no or mild supraglottic adduction in 114 (65%) patients, of whom 51 scored worse during CLE-test with moderate or severe supraglottic adduction. MVV at rest resulted in moderate or severe supraglottic adduction in 63 subjects, of whom 8 scored better during CLE-test with no or mild supraglottic adduction. Only 59% with moderate or severe supraglottic adduction at CLE-test had similar findings during MVV at rest.

Conclusion Laryngoscopy during MVV at rest has low sensitivity relative to supraglottic EILO diagnosed with CLE-test, findings that may have diagnostic and therapeutic consequences.

1 Maat RC et.al. Eur Arch Otorhinolaryngol 2009 .
Drug Supply Chain Security Act and Oral Anticancer Medications
Authors: Daniel M. Geynisman, Yu-Ning Wong
Journal: JAMA Oncology (2015)

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
In Vitro Induction of Malignant Transformation and In Vivo Resistance to Tumor Growth in the X/Gf Mouse&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: F Nahas, C Lichtig, H Gershon
Journal: JNCI Journal of the National Cancer Institute (1983)

Inbred X/Gf mice are reported to have a very low incidence of spontaneous and induced tumors. Experiments were performed to determine whether the cells of the X/Gf mouse are themselves resistant to in vitro oncogenesis or the organism as a whole is surveyed by a homeostatic mechanism that prevents the expression of potential neoplasia. Cultures of X/Gf or C57BL/6J embryonic fibroblasts were exposed to the chemical carcinogens 7,12-dimethylbenz[a]anthracene and benzo[a]pyrene to test whether the cells of the X/Gf mouse are themselves resistant to oncogenesis. The chemical carcinogens caused transformation of both X/Gf and C57BL/6 fibroblasts into cells that demonstrated altered growth patterns in liquid culture and grew in a clonal fashion in soft agar. Cloned transformed cells were shown to be malignant and resulted in the growth of sarcomas in vivo. X/Gf mice were decidedly more resistant than were C57BL/6 mice to their respective clones of transformed cells. The resistance to neoplastic growth demonstrated by the X/Gf mice was inherited by (C57BL/6J × X/Gf)F1 mice that were resistant to the growth of X/Gf-transformed and C57BL/6-transformed cells at cell doses at which the parental X/Gf mice had survived but at which the C57BL/6 had succumbed to progressively growing tumors. It has thus been established that the tumor resistance of the X/Gf mice is not based on the resistance of isolated cells from these animals to malignant transformation, but rather is attributable to an in vivo homeostatic mechanism that prevents tumor growth.
FOXO1 activation is an effector of SYK and AKT inhibition in tonic BCR signal-dependent diffuse large B-cell lymphomas
Authors: Maciej Szydlowski, Przemyslaw Kiliszek, Tomasz Sewastianik, Ewa Jablonska, Emilia Bialopiotrowicz, Patryk Gorniak, Anna Polak, Sergiusz Markowicz, Eliza Nowak, Monika A. Grygorowicz, Monika Prochorec-Sobieszek, Anna Szumera-Cieckiewicz, Agata Malenda, Ewa Lech-Maranda, Krzysztof Warzocha, Przemyslaw Juszczynski
Journal: Blood (2016)
Early spread of the 2009 influenza A(H1N1) pandemic in the United Kingdom – use of local syndromic data, May–August 2009
Authors: S Smith, G E Smith, B Olowokure, S Ibbotson, D Foord, H Maguire, R Pebody, A Charlett, J Hippisley-Cox, A J Elliot
Journal: Eurosurveillance (2011)

Following the confirmation of the first two cases of pandemic influenza on 27 April 2009 in the United Kingdom (UK), syndromic surveillance data from the Health Protection Agency (HPA)/QSurveillance and HPA/NHS Direct systems were used to monitor the possible spread of pandemic influenza at local level during the first phase of the outbreak. During the early weeks, syndromic indicators sensitive to influenza activity monitored through the two schemes remained low and the majority of cases were travel-related. The first evidence of community spread was seen in the West Midlands region following a school-based outbreak in central Birmingham. During the first phase several Primary Care Trusts had periods of exceptional influenza activity two to three weeks ahead of the rest of the region. Community transmission in London began slightly later than in the West Midlands but the rates of influenza-like illness recorded by general practitioners (GPs) were ultimately higher. Influenza activity in the West Midlands and London regions peaked a week before the remainder of the UK. Data from the HPA/NHS Direct and HPA/QSurveillance systems were mapped at local level and used alongside laboratory data and local intelligence to assist in the identification of hotspots, to direct limited public health resources and to monitor the progression of the outbreak. This work has demonstrated the utility of local syndromic surveillance data in the detection of increased transmission and in the epidemiological investigation of the pandemic and has prompted future spatio-temporal work.
Phase I/II storm study: Intravenous delivery of a novel oncolytic immunotherapy agent, Coxsackievirus A21, in advanced cancer patients
Authors: Hardev Pandha, Kevin Harrington, Christy Ralph, Alan Melcher, Mark Grose, Darren Shafren
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Coxsackievirus A21 (CVA21) is a naturally occurring "common cold" intercellular adhesion molecule-1 (ICAM-1)-targeted RNA virus. Surface ICAM-1 is up-regulated on a number of cancers including melanoma, non-small cell lung, bladder and prostate cancers. CAVATAK is a novel bio-
BALR-6 regulates cell growth and cell survival in B-lymphoblastic leukemia
Authors: Norma I. Rodríguez-Malavé, Thilini R. Fernando, Parth C. Patel, Jorge R. Contreras, Jayanth Kumar Palanichamy, Tiffany M. Tran, Jaime Anguiano, Michael J. Davoren, Michael O. Alberti, Kimanh T. Pioli, Salemiz Sandoval, Gay M. Crooks, Dinesh S. Rao
Journal: Molecular Cancer (2015)

A new class of non-coding RNAs, known as long non-coding RNAs (lncRNAs), has been recently described. These lncRNAs are implicated to play pivotal roles in various molecular processes, including development and oncogenesis. Gene expression profiling of human B-ALL samples showed differential lncRNA expression in samples with particular cytogenetic abnormalities. One of the most promising lncRNAs identified, designated B-ALL associated long RNA-6 (BALR-6), had the highest expression in patient samples carrying the MLL rearrangement, and is the focus of this study. Here, we performed a series of experiments to define the function of BALR-6, including several novel splice forms that we identified. Functionally, siRNA-mediated knockdown of BALR-6 in human B-ALL cell lines caused reduced cell proliferation and increased cell death. Conversely, overexpression of BALR-6 isoforms in both human and mouse cell lines caused increased proliferation and decreased apoptosis. Overexpression of BALR-6 in murine bone marrow transplantation experiments caused a significant increase in early hematopoietic progenitor populations, suggesting that its dysregulation may cause developmental changes. Notably, the knockdown of BALR-6 resulted in global dysregulation of gene expression. The gene set was enriched for leukemia-associated genes, as well as for the transcriptome regulated by Specificity Protein 1 (SP1). We confirmed changes in the expression of SP1, as well as its known interactor and downstream target CREB1. Luciferase reporter assays demonstrated an enhancement of SP1-mediated transcription in the presence of BALR-6. These data provide a putative mechanism for regulation by BALR-6 in B-ALL. Our findings support a role for the novel lncRNA BALR-6 in promoting cell survival in B-ALL. Furthermore, this lncRNA influences gene expression in B-ALL in a manner consistent with a function in transcriptional regulation. Specifically, our findings suggest that BALR-6 expression regulates the transcriptome downstream of SP1, and that this may underlie the function of BALR-6 in B-ALL.
Interim results of an ongoing Phase I, dose escalation study of MGA271 (Fc-optimized humanized anti-B7-H3 monoclonal antibody) in patients with refractory B7-H3-expressing neoplasms or neoplasms whose vasculature expresses B7-H3
Authors: John Powderly, Gregory Cote, Keith Flaherty, Russell Z Szmulewitz, Antoni Ribas, Jeffrey Weber, Deryk Loo, Jan Baughman, Francine Chen, Paul Moore, Ezio Bonvini, James Vasselli, Jon Wigginton, Roger Cohen, Howard Burris, Bartosz Chmielowski
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts MGA271 is a humanized IgG1 monoclonal antibody-targeting B7-H3 (CD276), a member of the B7 family. MGA271 has been Fc-engineered to enhance binding to activating FcγR (CD16A), decrease binding to inhibitory FcγR (CD32B), and potentiate ADCC. B7-H3 has limited expression in
Phase III, open-label, randomized, comparative study of tremelimumab (CP-675,206) and chemotherapy (temozolomide [TMZ] or dacarbazine [DTIC]) in patients with advanced melanoma
Authors: A. Ribas, A. Hauschild, R. Kefford, C. J. Punt, J. B. Haanen, M. Marmol, C. Garbe, J. Gomez-Navarro, D. Pavlov, M. Marshall
Journal: Journal of Clinical Oncology (2008)

LBA9011 Background: Tremelimumab, a fully human anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA4) monoclonal antibody was tested in a phase III study to compare the overall survival (OS) with standard, single-agent chemotherapy. Methods: Pts with unresectable stage IIIc-IV melanoma without brain metastasis, LDH below 2x ULN, and no prior systemic treatment for advanced melanoma were randomized 1:1 to either tremelimumab 15 mg/kg IV q90d, or physician's choice of TMZ 200 mg/m2 p.o. d1–5 q28d or DTIC 1,000 mg/m2 IV q21d (chemotherapy arm). Primary endpoint was OS, secondary endpoints included response, durable tumor response, 6-mo PFS, and safety. 537 deaths would provide 90% power to detect a 33% improvement in true median OS with an unstratified log-rank test at overall 2-sided significance level of 0.045. Two equally spaced interim analyses were planned based on the group sequential design using the Lan-DeMets alpha and beta spending approach to an O'Brien-Fleming boundary. Results: 655 pts were enrolled between March 2006 and July 2007, 328 pts randomized to tremelimumab (324 treated), 327 to chemotherapy (319 treated). There were no significant imbalances in age, sex, LDH, or stage (5% stage IIIc, 15% M1a, 22% M1b, 58% M1c). Diarrhea (43% overall, 14% grade 3/4), pruritus (25%) and rash (23%) were the most common treatment-related adverse events in the tremelimumab arm. 3% of pts had pituitary or adrenal gland toxicities, and 4% thyroid. There were 3 treatment-related deaths in the tremelimumab arm and none in the chemotherapy arm. Based on a protocol-specified second interim analysis with 340 deaths, the independent DSMC advised to stop the study on 3/28/08 since the Logrank test-statistic (P-value of 0.729) had crossed the O'Brien-Fleming futility boundary. Median OS by intent-to-treat was 11.8 mo (95% CI 10.4, 13.9) in the tremelimumab arm, and 10.7 mo (95% CI 9.3, 12.0) in the chemotherapy arm, with a HR (chemotherapy over tremelimumab) of 1.04 (95% CI 0.84, 1.28). Conclusions: Tremelimumab as a single agent failed to demonstrate an improvement in OS as a first line treatment in patients with metastatic melanoma when compared with standard chemotherapy. Analysis of secondary endpoints may provide further information on the role of tremelimumab in the management of metastatic melanoma. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Pfizer Pfizer Pfizer Pfizer Pfizer
A combination of pertuzumab, trastuzumab, and vinorelbine for first-line treatment of patients with HER2-positive metastatic breast cancer: An open-label, two-cohort, phase II study (VELVET).
Authors: Edith A. Perez, Jose Manuel Lopez-Vega, Lucia Del Mastro, Thierry Petit, Lada Mitchell, Christina H. Pelizon, Michael Andersson
Journal: Journal of Clinical Oncology (2012)

TPS653 Background: Pertuzumab (P) is a humanized monoclonal antibody directed against the dimerization domain of HER2: it prevents HER2 heterodimerization and thus activation of downstream signaling. Since P targets a different epitope than trastuzumab (H), a more comprehensive HER2 blockade is achieved by combining the two agents. Data from CLEOPATRA showed improved efficacy for P and H plus docetaxel. The combination of P and H has not yet been assessed with other chemotherapy partners in the metastatic setting. H plus vinorelbine (V) has shown comparable efficacy to H plus docetaxel but with a superior safety profile. VELVET will assess the overall response rate (ORR) of P with H+V in first-line patients (pts) with HER2-positive MBC. Co-administration of P and H within the same infusion bag will also be investigated as this could increase pt convenience by reducing administration and observation time. Methods: VELVET is a multicenter, open-label, two-cohort, Phase II trial. Pts with HER2-positive LABC or MBC not previously treated in the metastatic setting with non-hormonal anticancer therapy are eligible. Pts must have an LVEF &gt;55% at baseline and an ECOG PS of 0 or 1. Study enrollment started in January 2012. A total of 210 pts will be included. Based on statistical assumptions, 95 pts must be evaluable per cohort, which assumes a withdrawal rate around 10%. Pts in Cohort 1 (the first 105 pts enrolled) will receive P and H sequentially and pts in Cohort 2 (the next 105 pts) will receive P and H in the same infusion bag at Cycle 2 onwards if drug administration in Cycle 1 was well tolerated. V will be given in both cohorts. Treatment duration is until disease progression or unacceptable toxicity. Study dose: P: 840 mg loading dose, 420 mg q3w (iv); H: 8 mg/kg loading dose, 6 mg/kg q3w (iv), and V: 25 mg/m 2 Day 1 and 8 (first cycle) then 30−35 mg/m 2 Day 1 and 8 q3w (iv) (dose escalation at investigator’s discretion). The primary endpoint is ORR by independent assessment. Secondary endpoints include investigator assessment of ORR, time to response, duration of response, PFS, time to progression, overall survival, safety and tolerability, and QoL.
Development of a therapeutic monoclonal antibody that targets secreted fatty acid–binding protein aP2 to treat type 2 diabetes
Authors: M. Furkan Burak, Karen E. Inouye, Ariel White, Alexandra Lee, Gurol Tuncman, Ediz S. Calay, Motohiro Sekiya, Amir Tirosh, Kosei Eguchi, Gabriel Birrane, Daniel Lightwood, Louise Howells, Geofrey Odede, Hanna Hailu, Shauna West, Rachel Garlish, Helen Neale, Carl Doyle, Adrian Moore, Gökhan S. Hotamisligil
Journal: Science Translational Medicine (2015)

A monoclonal antibody to fatty acid–binding protein aP2 has antidiabetic effects on glucose output and utilization.
LCIS: Is tamoxifen a rational chemoprevention choice?
Authors: G. H. Perkins, L. P. Middleton, A. A. Sahin, S. E. Singletary
Journal: Journal of Clinical Oncology (2005)

1012 Body: Purpose: Tamoxifen is a proven chemopreventive modality that reduces the risk of invasive breast cancer by over 50% in high risk women. LCIS is a known risk factor for the development of breast cancer; however, the use of tamoxifen for prevention in LCIS is based upon data for ER+ receptor status of LCIS associated with invasive cancer. Tamoxifen use in randomized trials has been beneficial for ER+ patients. There is no published literature on hormone receptor status of LCIS not associated with invasive cancer. We therefore examined the receptor status of patients with ALH and LCIS not associated with invasive breast cancer to identify patients that may not benefit from tamoxifen therapy. Methods: Core biopsy material of 50 patients diagnosed with ALH and LCIS between 1999 and 2004 at UTMDACC was examined. Histology was reviewed. The presence or absence of co-existing pathology was noted. E-cadherin and ER immunological staining was performed with adequate controls. Statistics were analyzed using STATA software package. Results: Mean patient age was 55 years (range 37–79 years). Mean Follow-up was 36 months. 35 patients had ALH by criteria; 15 had LCIS. Nuclear grade was as follows: grade 1 (n=48); grade 2 (n=2). LCIS with central necrosis was noted in 1 patient. Columnar cell alterations and fibrocystic changes were noted in 10% and 14% of patients respectively. All patients were E cadherin negative. With respect to ER receptor status, all 50 patients were ER+ (median 75% staining intensity; range 10% [weak positive] - 100% [strong positive]) (p<0.05). No correlation was noted between histological features and intensity of ER staining (p>0.05). Conclusions: This study is the first report of ER receptor status in LCIS/ALH not associated with invasive cancer. In our cohort, 100% of patients were ER + and we were unable to identify histologic features indicative of weak ER positivity. This study confirms the hormonal influence in the development and biology of ALH/LCIS, and validates the consideration of tamoxifen as a component of quality preventive patient care. Further studies may elucidate predictive factors for weak ER positivity and indentify patients least likely to benefit from this preventive strategy. No significant financial relationships to disclose.
Oral contraceptives and alopecia.
Authors: A E Greenwald
Journal: BMJ (1968)

Exfoliative cytology of the colon' is difficult because of faecal debris.Painstaking bowel preparation and skilful interpretation of the cytological findings are essential, so that it is doubtful whether this method has a role in screening.How then can tumours of the large bowel be diagnosed at 'their earliest stage ?In practice this implies constant clinical awareness.Slight changes in bowel habit or rectal bleeding must be regarded as danger signs which are not to be ignored.The test for occult blood in the stools is simple and even if bedevilled by false positive and negative results at least it gives some rough screening in a symptomatic patient.If the test is performed on several specimens a false negative is unlikely to occur.The sigmoidoscope is easy to use and should be employed at every opportunity in routine examinations; two-thirds of large bowel growths are within its reach, and, perhaps more important, polyps can be detected and removed before malignant change can take place.
DNA–gadolinium–gold nanoparticles for in vivo T1 MR imaging of transplanted human neural stem cells
Authors: Francesca J. Nicholls, Matthew W. Rotz, Harmanvir Ghuman, Keith W. MacRenaris, Thomas J. Meade, Michel Modo
Journal: Biomaterials (2015)

The unambiguous imaging of transplanted cells remains a major challenge to understand their biological function and therapeutic efficacy. In vivo imaging of implanted cells is reliant on tagging these to differentiate them from host tissue, such as the brain. We here characterize a gold nanoparticle conjugate that is functionalized with modified deoxythymidine oligonucleotides bearing Gd(III) chelates and a red fluorescent Cy3 moiety to visualize in vivo transplanted human neural stem cells. This [email protected] nanoparticle ([email protected]) exhibits an improved T1 relaxivity and excellent cell uptake. No significant effects of cell uptake have been found on essential cell functions. Although T1 relaxivity is attenuated within cells, it is sufficiently preserved to afford the in vivo detection of transplanted cells using an optimized voxel size. In vivo MR images were corroborated by a post-mortem histological verification of [email protected] in transplanted cells. With 70% of cells being correctly identified using the DNA-Gd-AuNPs indicates an overall reliable detection. Less than 1% of cells were false positive for [email protected], but a significant number of 30% false negatives reveals a dramatic underestimation of transplanted cells using this approach. [email protected] therefore offer new opportunities to visualize transplanted cells unequivocally using T1 contrast and use cellular MRI as a tool to derive biologically relevant information that allows us to understand how the survival and location of implanted cells determines therapeutic efficacy.