tbuckley/cabot-search huggingface dataset:
TOPICAL: Randomized phase III trial of erlotinib compared with placebo in chemotherapy-naive patients with advanced non-small cell lung cancer (NSCLC) and unsuitable for first-line chemotherapy.
Authors: S. Lee, R. Rudd, I. Khan, S. Upadhyay, C. R. Lewanski, S. Falk, G. Skailes, R. Partridge, Y. Ngai, C. Boshoff
Journal: Journal of Clinical Oncology (2010)

7504 Background: Poor performance status (PS) NSCLC is an important, under-studied group of lung cancer patients, affecting 30-40% of patients. We determined the role of erlotinib plus best supportive care (BSC) in chemo-naïve, poor PS advanced NSCLC patients. Methods: Chemo-naïve NSCLC patients (ECOG PS 2/3 or PS 0/1 unfit for platinum chemotherapy; stage IIIB/IV) were randomized to erlotinib (150 mg/d) plus BSC (n = 350) or placebo plus BSC (n = 320). Endpoints were overall survival (OS), progression-free survival (PFS), response rate, and toxicity. The trial had 90% power to detect an increase in 1-year OS from 10% to 17.5%. Results: Between 2005 and 2009, 670 patients were randomised to either erlotinib (350) or placebo (320), from 78 UK centres. Median age was 77 yrs (range 42-91); 61% male; 38% adenocarcinoma, 39% squamous histology; the % with ECOG PS score of 0/1, 2 and 3 were 16%, 55% and 29% respectively; 35% stage IIIB and 65% stage IV disease. Baseline patient characteristics were balanced between the groups. At the time of analysis, 559 patients had died. Hazard ratio (HR; erlotinib vs placebo) for OS was 0.98 [95% CI 0.82-1.15; p = 0.77]. PFS HR was 0.86 [0.74-1.01, p = 0.07]. Pre-specified subgroup analyses showed significant longer OS and PFS for females only: HR of 0.75 [0.57-0.99, p = 0.04] and 0.64 [0.49-0.83, p = < 0.001] respectively. PFS HR for adenocarcinoma was 0.74 [0.57-0.97, p = 0.03]. PFS HR according to gender and histology were: 0.68 [0.46-0.99, p = 0.046] females with adenocarcinoma; 0.62 [0.43-0.89, p = 0.01] females with non-adenocarcinoma; 0.85 [0.59-1.22, p=0.37] males with adenocarcinoma; and 1.14 [0.89-1.45, p = 0.31] male with non- adenocarcinoma. As expected, increased Grade 3/4 rash and diarrhoea were observed in patients receiving erlotinib. Conclusions: Overall, erlotinib plus BSC did not improve OS, but there was some evidence of benefit for PFS. However, there was a clear effect on both OS and PFS for females, and PFS for adenocarcinoma. However, the effect in adenocarcinoma was largely driven by female patients. Final analyses, including EGFR mutation, VeriStrat serum tests and QoL will be presented. No significant financial relationships to disclose.
Hyperactivation of JAK1 tyrosine kinase induces stepwise, progressive pruritic dermatitis
Authors: Takuwa Yasuda, Toshiyuki Fukada, Keigo Nishida, Manabu Nakayama, Masashi Matsuda, Ikuo Miura, Teruki Dainichi, Shinji Fukuda, Kenji Kabashima, Shinji Nakaoka, Bum-Ho Bin, Masato Kubo, Hiroshi Ohno, Takanori Hasegawa, Osamu Ohara, Haruhiko Koseki, Shigeharu Wakana, Hisahiro Yoshida
Journal: Journal of Clinical Investigation (2016)

Skin homeostasis is maintained by the continuous proliferation and differentiation of epidermal cells. The skin forms a strong but flexible barrier against microorganisms as well as physical and chemical insults; however, the physiological mechanisms that maintain this barrier are not fully understood. Here, we have described a mutant mouse that spontaneously develops pruritic dermatitis as the result of an initial defect in skin homeostasis that is followed by induction of a Th2-biased immune response. These mice harbor a mutation that results in a single aa substitution in the JAK1 tyrosine kinase that results in hyperactivation, thereby leading to skin serine protease overexpression and disruption of skin barrier function. Accordingly, treatment with an ointment to maintain normal skin barrier function protected mutant mice from dermatitis onset. Pharmacological inhibition of JAK1 also delayed disease onset. Together, these findings indicate that JAK1-mediated signaling cascades in skin regulate the expression of proteases associated with the maintenance of skin barrier function and demonstrate that perturbation of these pathways can lead to the development of spontaneous pruritic dermatitis.
Cetuximab and EGFR inhibitors in patients with neurological symptoms due to chordoma.
Authors: Ola Linden, Mats Ehinger, Sara Kinhult, Thomas Relander, Lotta Lundgren, Jakob Engellau, Elisabeth Kjellén
Journal: Journal of Clinical Oncology (2012)

10024 Background: Chordomas are rare tumours located along the neuraxis, showing limited sensitivity to radiotherapy and lack of response to chemotherapy. However, tyrosine kinase inhibitors (TKIs) have been reported to have an effect. Following the failure of single-agent treatment in a young patient using cetuximab, we decided to treat patients (pts) with neurological symptoms with dual targeting of the epidermal growth factor receptor (EGFR), based on a case report by Hof et al., who successfully used dual targeting of EGFR, and supporting in vitro data. Methods: Eight consecutive pts with neurological symptoms at referral were treated with cetuximab (250 mg/m 2 weekly) and an EGFR signalling inhibitor (250 mg gefitinib or 150 mg erlotinib daily). The duration of treatment was not decided in advance. Results: EGFR expression on tumour cells was variable but present in all pts. Six pts were evaluable. One tetraplaegic pt died of an unknown cause and one pt on lithium carbonate discontinued treatment before the first follow-up due to renal toxicity. Four pts showed neurological improvement. Two of these regained and one improved the ability to walk, and a fourth, with a sacral tumour, improved his voiding ability. The fifth pt had clinically stable disease and, although the PET scan showed improvement, the treatment had to be discontinued due to skin toxicity. One pt showed progressive disease. In the four pts responding neurologically, improvement was noted already by the end of the third week. Three pts were retreated without failure while on treatment. The first pt who regained the ability to walk is still walking at 52+ months. This pt, while still responsive to cetuximab and erlotinib, has failed to respond to single-agent treatment with imatinib, sorafenib or everolimus. The second pt who regained walking ability had severe alcoholism and died while being treated. The third is still walking at 16+ months. All pts exhibited significant cutaneous side effects, in some cases necessitating intermittent interruption of therapy. Conclusions: Treatment with cetuximab and TKIs can thus achieve meaningful and long-lasting clinical improvement in pts with paresis due to chordoma, and is feasible in pts with limited comorbidities.
Family Perspectives on Aggressive Cancer Care Near the End of Life
Authors: Joan M. Teno, J. Randall Curtis
Journal: JAMA Oncology (2016)

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
A man with altered mental status and metabolic acidosis
Authors: Abhishek Maiti, Avash Das
Journal: BMJ (2016)

A 52 year old man was brought to the emergency department for acute onset shortness of breath and confusion. On physical examination he was agitated and taking deep breaths at the rate of 28/min. Initial venous blood gas on ambient air showed pH 7.02, partial pressure of carbon dioxide 3.4 kPa, partial pressure of oxygen 4.1 kPa. …
Colorectal Cancer Screening Based on Age and Gender: A Cost-effectiveness Analysis
Authors: Martin C.S. Wong, Victor C.W. Chan, Jeffrey P. Shum, Jessica Y.L. Ching, Simon S.M. Ng, Thomas Y.T. Lam, Arthur K.C. Luk, Sunny H. Wong, Siew C. Ng, Justin C.Y. Wu, Francis K.L. Chan, Joseph J.Y. Sung
Journal: Clinical Gastroenterology and Hepatology (2015)
Data science for mental health: a UK perspective on a global challenge
Authors: Andrew M McIntosh, Robert Stewart, Ann John, Daniel J Smith, Katrina Davis, Cathie Sudlow, Aiden Corvin, Kristin K Nicodemus, David Kingdon, Lamiece Hassan, Matthew Hotopf, Stephen M Lawrie, Tom C Russ, John R Geddes, Miranda Wolpert, Eva Wölbert, David J Porteous
Journal: The Lancet Psychiatry (2016)
Rebuilding the front line
Authors: Sophie Cook
Journal: BMJ (2016)

GPs are overstretched, out-of-hours care is disorganised, and this week history was in the making, as junior doctors in England staged their first ever all-out strike (doi: 10.1136/bmj.i2404, doi:10.1136/bmj.i2382). The NHS front line is fragmented, strained, and in dire need of help.

“If general practice fails, the NHS fails,” said Martin Roland and Sam Everington in a recent BMJ editorial (doi:10.1136/bmj.i942). They called for substantial investment to redress the balance that has favoured hospital services in …
Quantifying Treatment Benefit in Molecular Subgroups to Assess a Predictive Biomarker
Authors: Alexia Iasonos, Paul B. Chapman, Jaya M. Satagopan
Journal: Clinical Cancer Research (2016)

An increased interest has been expressed in finding predictive biomarkers that can guide treatment options for both mutation carriers and noncarriers. The statistical assessment of variation in treatment benefit (TB) according to the biomarker carrier status plays an important role in evaluating predictive biomarkers. For time-to-event endpoints, the hazard ratio (HR) for interaction between treatment and a biomarker from a proportional hazards regression model is commonly used as a measure of variation in TB. Although this can be easily obtained using available statistical software packages, the interpretation of HR is not straightforward. In this article, we propose different summary measures of variation in TB on the scale of survival probabilities for evaluating a predictive biomarker. The proposed summary measures can be easily interpreted as quantifying differential in TB in terms of relative risk or excess absolute risk due to treatment in carriers versus noncarriers. We illustrate the use and interpretation of the proposed measures with data from completed clinical trials. We encourage clinical practitioners to interpret variation in TB in terms of measures based on survival probabilities, particularly in terms of excess absolute risk, as opposed to HR. Clin Cancer Res; 22(9); 2114-20. ©2016 AACR.
Case 37-1970
Authors: Richard C. Cabot, Benjamin Castleman, Betty U. McNeely, James B. Wyngaarden, Benjamin Castleman
Journal: New England Journal of Medicine (1970)

PRESENTATION OF CASE First admission A 32-year-old man was admitted to the hospital because of arthritis and cutaneous lesions.He had been well until 15 years previously, when he began to experience morning stiffness in the shoulders, elbows and wrists; the joints were never red or tender; he was treated initially with aspirin and later with phenylbutazone. Seven years before admission pain in the hips developed, and adrenocorticosteroid treatment was begun. The joint pain progressed in severity, with involvement of the hands, feet, elbows, knees, shoulders and hips; there was crackling of the temporomandibular joints, but the neck and the . . .
TCTAP C-137 Two Years Follow-up of a Case with Peri-stent Contrast Staining After Implanting 2 Types of Second-generation Drug-eluting Stents, Resulted in Coronary Thrombosis During Intravascular Ultrasound Procedure
Authors: Tetsuro Kataoka, Kazuhiro Anzaki
Journal: Journal of the American College of Cardiology (2016)
AB0045 Complement Analysis Reveals New Biomarker in Patients with Juvenile Idiopathic Arthritis
Authors: J. Brunner, L. Hackl, R. Wuerzner, T. Giner
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> The juvenile idiopathic arthritis is a well researched disease in the group of autoimmunopathies. Beside the deregulation of T-cells and cytokines also the complement system is involved in the pathogenesis of this group of diseases. <h3>Objectives</h3> This prospective longitudinal study investigated the contribution of the complement system in patients with juvenile idiopathic arthritis, using practicable ELISA techniques (Wieslab® screening kit; SC5b9 soluble terminal complement complex ELISA). <h3>Methods</h3> Serum and plasma of the peripheral blood and the synovial fluid were investigated for the activity of the three complement pathways - classical (CP), mannose binding lectin (MBL), and the alternative pathway (AP) and total complement activity by measuring SC5b9. Results where compared to published reference controls and 18 children without activation of inflammation as an age matched control group. In total 57 samples of peripheral blood (PB) and 8 samples from synovial fluid (SF) from 28 children with JIA were investigated in a longitudinal observation during acute phase and remission. <h3>Results</h3> The screening of complement system showed debasement of the AP (8 of 10) and CP (7 of 10) in patients during acute phase (7 of 10). The SC5b9 measurement showed a significant (p&lt;0.002) higher amount in plasma (3,6AU/ml in median) and serum (31,4AU/ml) during acute phase compared to the control group (serum - 7,72AU/ml and plasma – 1,25AU/ml in median). <h3>Conclusions</h3> In conclusion the study confirmed, that the CP and AP of the complement system are main contributors in the pathogenesis of JIA. Because of significant elevation of SC5b9 in acute phase of JIA, complement blockade with Anti-C5 may be a therapeutically option in the future. <h3>References</h3> Brunner J, et al Rheumatology International 32:1815–1818; 2012 <h3>Acknowledgements</h3> Austrian Society for Rheumatology and Rehabilitation <h3>Disclosure of Interest</h3> None declared
Results of the phase I trial of cetuximab with mitomycin c and 5-fluorouracil concurrent with radiotherapy treatment in patients with muscle-invasive bladder cancer.
Authors: Syed A. Hussain, Carey Hendron, Laura Buckley, Lynne Dickinson, Isabel Syndikus, Zafar Malik, Chinnamani Eswar, Nicholas David James
Journal: Journal of Clinical Oncology (2015)

368 Background: Synchronous chemo-radiotherapy is an alternative to cystectomy in patients with muscle invasive bladder cancer (MIBC). BC2001 trial reported improved local control in patients randomised to synchronous chemo-radiotherapy compared to radiotherapy alone (James, Hussain, Hall et al NEJM 2012). TUXEDO trial reports phase I trial results with additional weekly cetuximab (Cet) in combination with Mitomycin c (MMC), 5-Fluouracil (5-FU) and concurrent radiotherapy (RT). Methods: This two centre phase I trial recruited 7 patients with MIBC in Queen Elizabeth Hospital Birmingham and Clatterbridge Cancer Centre Liverpool to synchronous chemotherapy using Loading dose of Cet 400 mg/m2 followed by weekly Cet 250 mg/m2, continuous infusion 5-FU 500mg/m 2 /day during fractions 1-5 and 16-20 of RT and MMC12mg/m 2 on day 1 in combination with radical RT treatment 64 Gys in 32 fractions. The primary endpoint was to assess toxicity. Secondary end- points included 3 months pathological complete response, loco-regional disease-free survival and overall survival. Results: Median age of patients was 70 (range: 60-75) years, all were male, 6 had received prior neoadjuvant chemotherapy. Two patients had T2B, 3 T3A and 2 T3B disease, all had G3, TCC disease, 6 patients had neo-adjuvant chemotherapy. All 7 patients completed RT as planned except for 1 who withdrew from trial after 5 weeks of protocol treatment due to relocation. Median dose intensity for Cet and MMC was 97.6% and for 5-FU was 99.4%. Grade 3 toxicity to report was maculopapular rash in 3 patients. Grade 2 toxicities include UTI/ frequency/ nocturia / fatigue /constipation / hypokalemia/epistaxis/palmar-plantar reported in 3/1/1/1/1/1/1/2 cases respectively. Grade 2 maculo-papular rash was reported in 3 cases. All seven patients have achieved complete responses at 3 months cystoscopic assessment. Patients continue on surveillance as per TUXEDO trial protocol. Conclusions: Synchronous chemotherapy with Cet and 5FU/MMC concurrent with radical RT is safe to deliver. Complete response rates are encouraging and a phase II trial with added centres within UK is being launched. Clinical trial information: NOT KNOWN.
Risk for Hospitalized Heart Failure Among New Users of Saxagliptin, Sitagliptin, and Other Antihyperglycemic Drugs
Authors: Sengwee Toh, Christian Hampp, Marsha E. Reichman, David J. Graham, Suchitra Balakrishnan, Frank Pucino, Jack Hamilton, Samuel Lendle, Aarthi Iyer, Malcolm Rucker, Madelyn Pimentel, Neesha Nathwani, Marie R. Griffin, Nancy J. Brown, Bruce H. Fireman
Journal: Annals of Internal Medicine (2016)

Recent postmarketing trials produced conflicting results about the risk for hospitalized heart failure (hHF) associated with dipeptidyl peptidase-4 (DPP-4) inhibitors, creating uncertainty about the safety of these antihyperglycemic agents.
Effect of Oxygen on the Cytotoxicity and Antitumor Activity of Etoposide&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: B A Teicher, S A Holden, C M Rose
Journal: JNCI Journal of the National Cancer Institute (1985)

The selective cytotoxicity of the epipodophyllotoxin etoposide toward normally oxygenated and hypoxic EMT6 mouse mammary tumor cells in culture was examined. Etoposide was much more toxic to normally oxygenated cells. The ratio (hypoxic to oxygenated) of drug concentrations producing 1 log of cell kill was approximately 30:1. Established FSa-11C fibrosarcomas of C3HeB/FeJ mice were treated with 10, 15, or 20 mg etoposide/kg body weight in a 6-day protocol. Fluosol-DA with or without breathing of carbogen (i.e., 95% O2-5% CO2) was added to the treatment program on days 1, 3, and 5. The combination of etoposide-Fluosol-DA-carbogen markedly enhanced tumor growth delay compared to the result with etoposide alone. The dose-modifying effect observed was 1.9 +/- 0.3. With the use of both single-dose and multiple-dose protocols for etoposide and Fluosol-DA with air or carbogen breathing, the survival of bone marrow cells was measured by colony formation in vitro (granulocyte-monocyte colony-forming units). Fluosol-DA and carbogen breathing did not increase the toxicity of etoposide to the bone marrow. Thus the enhancement in antitumor activity produced by the addition of Fluosol-DA and carbogen breathing to etoposide treatment was not accompanied by a concomitant increase in normal tissue toxicity and represents an increase in the therapeutic efficacy of etoposide.
Development of dedifferentiated liposarcoma during JAK inhibitor treatment in a rheumatoid arthritis patient
Authors: Atsushi Iwashige, Makoto Hirosawa, Takefumi Katsuragi, Hiroaki Morimoto, Takehiro Higashi, Aya Tanaka, Takahiro Yamaguchi, Noriaki Kitamura, Ai Kawahara, Junichi Tsukada
Journal: Annals of Oncology (2015)
Abstract 5501: Antagonism of sorafenib and regorafenib actions by epidermal growth factor in hepatoma cells
Authors: Brian I. Carr, Rosalba D'Alessandro, Maria Grazia Refolo, Catia Lippolis, Caterina Messa, Aldo Cavallini
Journal: Cancer Research (2015)

Abstract Background. Platelet numbers are related to growth and aggressiveness of several tumor types, including hepatoma (hepatocellular carcinoma). We previously found that platelet lysates also stimulated growth and migration of hepatoma lines in vitro and antagonized the growth-inhibitory effects on hepatoma cells of both multikinase inhibitors sorafenib and regorafenib (BMC Cancer 2014; 14:351). Aims. To investigate the mechanisms for the platelet-mediated multikinase drug resistance, we examined the actions of several mitogens that are known to be contained by platelets (PDGF, VEGF, TGF beta, FGF, IGF-1, EGF). Results. We found that epidermal growth factor (EGF) alone antagonized the growth inhibitory actions of Sorafenib or Regorafenib on HepG2, PLC/PRF/5 and Hep3B human hepatoma cells, using an MTT assay. Detailed studies revealed that EGF also antagonized Regorafenib-mediated inhibition of cell migration and invasion. Furthermore, EGF also blocked regorafenib-induced apoptosis, measured by Annexin V using a MUSE cell analyzer. These effects of EGF were antagonized by concomitant addition to the cultures of EGF receptor antagonist Erlotinib, showing that the EGF receptor was involved in the mechanisms of EGF-mediated blocking of Regorafenib effects. In addition, Erlotinib also partially blocked the effects of platelet lysates in antagonizing regorafenib-mediated growth inhibition. Similar antagonism was found using IGF-1, and those effects were blocked by GSK IGF-1 receptor antagonist. Other platelet factors had only weak actions in these assays. Conclusions. EGF antagonized regorafenib-mediated growth and migration inhibition and apoptosis induction in hepatoma cells. These EGF actions were mediated via the EGF receptor, as were the similar platelet lysate actions. Citation Format: Brian I. Carr, Rosalba D'Alessandro, Maria Grazia Refolo, Catia Lippolis, Caterina Messa, Aldo Cavallini. Antagonism of sorafenib and regorafenib actions by epidermal growth factor in hepatoma cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5501. doi:10.1158/1538-7445.AM2015-5501
Enrollment Criteria Controversies for Active Surveillance and Triggers for Conversion to Treatment in Prostate Cancer
Authors: David D. Buethe, Julio Pow-Sang
Journal: Journal of the National Comprehensive Cancer Network (2012)

In the era of widespread prostate-specific antigen screening, low-risk and very-low-risk prostate cancers are commonly identified, many of which will be of clinical insignificance. This has led to overtreatment and undue exposure to treatment-related morbidity in men harboring indolent tumors. Over the past 10 years, active surveillance (AS) has been evolving as a management strategy for these cancers. With continual reevaluation, the intent is to definitively treat tumors that are clearly progressive before the window of opportunity for cure has closed. To date, many of the surveillance parameters are without validation of utility, variably used, and without a standardized schedule. However, new instruments for characterizing prostate cancer offer the potential to better distinguish which men are best managed definitively at the outset from those who would be better served with observation. The findings of currently available AS cohorts suggest that initial expectant management of early prostate cancer is reasonable, showing that only approximately 30% of observed tumors are reclassified to ones of intermediate risk with short-term follow-up. Prostate cancer survival for men undergoing AS is close to 100% in all available studies, but long-term data remain scarce for those requiring delayed curative therapy.