tbuckley/cabot-search huggingface dataset:
Changes in gene expression that accompany the immortalization or transformation of human bronchial epithelial cells
Authors: Chunyu Zhang, Abdel G. Elkahloun, Phillip A. Dennis
Journal: Cancer Research (2004)

Proc Amer Assoc Cancer Res, Volume 45, 2004

1720 

Lung cancer, the most lethal cancer worldwide, is mostly caused by smoking and is characterized by complex genetic, epigenetic and biochemical changes in epithelial tissue. Previously, our laboratory showed that two tobacco components, nicotine or the tobacco specific carcinogen, NNK, activate the PI3K/Akt pathway in a phenotypic spectrum of lung epithelial cells and partially induce a transformed phenotype in primary human bronchial epithelial cells. Because Akt activation alters the activity of transcription factors such as forkhead family members, and because the genetic and epigenetic changes that accompany transformation of human lung epithelial cells are not known, we performed gene expression profiling of normal human bronchial epithelial cells (NHBE), NHBE cells immortalized by SV40 (BEAS-2B), isogenic BEAS-2B cells fully transformed by the tobacco-specific carcinogen NNK (NNK-BEAS-2B), as well as a squamous cell lung cancer cell line (H157). From an analysis of 28,798 cDNA clones, a total of 1,053 identifiable genes were differentially expressed in BEAS-2B, NNK-BEAS-2B or H157 cells, compared to NHBE. Immortalization was characterized by changes in 191 genes (73 upregulated, 118 downregulated), and transformation by 689 genes (285 upregulated, 404 downregulated). Gene expression profiles were further validated at the protein level for 27 molecules using immunoblot analysis. During immortalization, we observed increased levels of CDC2, CENPE, cyclin A, MAD2L1, PRO2000, PCNA, RRM2 and TOP2A, as well as oncogenes such as DEK, PTTG1 and stathmin 1. In contrast, differentiation markers such as keratin family member KRT5, KRT6A, KRT6B, KRT14 and KRT16, and NDRG1 were downregulated in immortalization, as were the CDK inhibitor p21 and tumor suppressor genes such as CHK2, PERP, S100 calcium binding protein S100A2, S100A6, S100A8 and S100A9, p63, PAI-2, maspin and TRAIL. Transformation was characterized by overexpression of survivin, CENPF, cyclin B2, Cyr61, DKK1, FKBP1A, hnRNPA2/B1, HMG1, galectin 1, MCM2, MCM4, MCM7, neuregulin 2, NEK2, ANKT, PBK, TACC3, CDC20, CDC45L, cyclin F, cyclin G1, CDK2, DNMT1, EIF5A, HIP1, NNMT, PLK1, SPARC, STK15, STK18, TACC1, TROP1 and ETS1, and suppression of 15-LOX2, p15, FAT2, FKHR, GADD45G, GAS2, ING1, RIN1, SERPINB3 and TAO1. These studies are the first to identify changes in gene expression that accompany the phenotypic progression of human lung epithelial cells, and identify targets that might be exploited to prevent the phenotypic transformation of lung epithelial cells.
PTU-300 Enhancing patient care by total integration of multidisciplinary skills
Authors: E Hills, A St. Clair Jones
Journal: Gut (2015)

<h3>Introduction</h3> A multidisciplinary team (MDT) is essential to ensure high quality and compassionate care for patients with longterm diseases. We established a holistic care model using a MDT approach to provide support through easily accessible services and permeable pathways. In addition to the medical/nursing staff a post for a pharmacist was incorporated into the team; this complemented and highlighted total integration of roles. Multidisciplinary services are widely reported but having nursing/pharmacy staff sharing responsibility for patients care is innovative and new ways of working were explored in the redesigning of our IBD service. <h3>Method</h3> Clear pathways were developed to ensure patients attended appropriate clinics and enabled reviews with the correct team member. Therapeutic drug monitoring (TDM) was newly introduced to optimise medical treatment. At the MDM pathways were developed to initiate and review immunomodulators and were facilitated by the nurse/pharmacist. <h3>Results</h3> Established patients were seen for follow ups mainly by the nurse specialist. One pharmacist clinic was established weekly. Referrals to the pharmacist clinic consisted of patients needing to initiate and optimisation of immunomodulating therapies, adverse drug reactions (ADRs) or with perceived concordance issues. The nurse/pharmacist clinics are well used with 10 patients per clinic supporting the effectiveness of the new developed pathways. Interdisciplinary support was provided to enable the nurse/pharmacy team to deputise for each other when answering the patient helpline/email queries and undertaking the TDM for patients on immunosuppressants. The helpline had an average of 11 calls per day. In the 4 months analysed 1032 calls were managed of which the pharmacist answered 142 queries whilst deputising. Due to the involvement of the pharmacist early adoption of innovative TDM was established.47 patients had their immunosupressant therapy changed or stopped, resulting in a minimum of £50,000 savings in the initial 4 months. The infusion clinic was expanded to include cross speciality patients on immunosuppressants, nutritional supplements and iron due to the involvement of the pharmacist guaranteeing effective support for non speciality patients. The MDM reviewed 42 patients according to the developed pathways. 10 patients considered eligible for biologics/7 patients needed their therapy altered. <h3>Conclusion</h3> Interprofessional relationships profit greatly when working closely and deputising for each other. Providing support for each other when taking over responsibility for non traditional roles proved to be an effective way of enhancing patient safety. Permeable pathways and standardisation of treatments including consistent monitoring provided sound governance for individualised medical care. <h3>Disclosure of interest</h3> None Declared.
Triple receptor comparison between primary breast cancer and metachronous or synchronous liver metastasis
Authors: Sebastiaan Tuyls, Olivier Brouckaert, Adriaan Vanderstichele, Joke Vanderhaegen, Frédéric Amant, Karin Leunen, Ann Smeets, Patrick Berteloot, Erik Van Limbergen, Caroline Weltens, Stéphanie Peeters, Dirk Vanbeckevoort, Beppe Floris, Philippe Moerman, Robert Paridaens, Hans Wildiers, Ignace Vergote, Rose Christiaens, Patrick Neven
Journal: Cancer Research (2012)
Competency-based psychiatric education
Authors: H M Weinstein, M L Russell
Journal: American Journal of Psychiatry (1976)

The focus of training in a competency-based residency program is on ensuring that all residents attain prespecified levels of competence for particular objectives in each training activity. The authors examine the components of a competency-based program and describe the phases of development that their department went through in creating such a program. They conclude that the competency-based training model directly faces the issue of certifying competence by holding itself accountable in a demonstrable way for ensuring that its residents have mastered specific areas of knowledge, skills, and attitudes.
Identification of Japanese Apricot Peamaclein As a New Allergen Related to Food-Dependent Exercise-Induced Anaphylaxis Due to Japanese Apricot: Cross-Reactivity to Pru p 7
Authors: Naoko Inomata, Mami Miyakawa, Asa Hotta, Michiko Aihara
Journal: Journal of Allergy and Clinical Immunology (2016)
PD-012 Validation study of the 12-gene Recurrence Score (RS) in patients (pts) with stage II and III colon cancer (CC) without adjuvant chemotherapy; SUNRISE Study
Authors: M. Ikeda, T. Yamanaka, K. Yamazaki, K. Yamaguchi, K. Muro, T. Kusumoto, H. Uetake, T. Sato, T. Kato, T. Nishina, A. Kanazawa, E. Oki, C. Chao, T. Maddala, J. Krishnakumar, K. Akagi, A. Ochiai, Y. Ohashi, A. Ohtsu, T. Yoshino
Journal: Annals of Oncology (2015)
Using the Internet to Identify Infectious-Disease Outbreaks
Authors: Eric V. Granowitz, Arjun Srinivasan, Neville D. Clynes
Journal: New England Journal of Medicine (2004)

To the Editor: The Emerging Infections Network (EIN) is a health care provider–based, sentinel network that was established in 1996. Its central feature is an e-mail list (listserv) with 946 participants from all 50 states and 36 foreign countries. The majority of participants are infectious-disease consultants in academia or private practice; 16 percent work in the public health sector. Participants communicate by means of a closed electronic mail system and Web site.1 The purposes of EIN are to detect new infectious diseases or outbreaks, identify cases during investigations of outbreaks, acquire knowledge rapidly about newer infections, facilitate research, and foster . . .
Case 2-2008
Authors: Colm C. Magee, Matthew P. Coggins, C. Stephen Foster, Victorine V. Muse, Robert B. Colvin
Journal: New England Journal of Medicine (2008)

A 38-year-old woman was admitted to the hospital 2 weeks after delivery because of loss of vision, shortness of breath, and renal failure. Preeclampsia had developed during pregnancy, and cesarean section was performed at 25 weeks' gestation. The day after delivery, blurred vision and scotomata developed and persisted. Intravenous corticosteroid therapy was begun, but shortness of breath developed, and the patient was admitted to the hospital.
Skin toxicity associated with pegylated liposomal doxorubicin (40 mg/m<sup>2</sup>) in the treatment of gynecologic cancers
Authors: R. J. Kim, G. Peterson, B. Kulp, K. M. Zanotti, M. Markman
Journal: Journal of Clinical Oncology (2004)

5080 Background: Pegylated liposomal doxorubicin (PLD) is a chemotherapeutic agent used in the management of myriad gynecologic cancers. Although it is proposed to have less side effects than doxorubicin, PLD is associated with significant skin reactions. The incidence of skin toxicity of PLD administered at a lower dose (40 mg/m2) is not well-characterized. Methods: Medical charts of all patients who initiated PLD at a starting dose of 40 mg/m2 from 1997–2003 for the treatment of gynecologic cancers were retrospectively reviewed. PLD was infused over 1–2 hours and administered every 4–6 weeks. No patient had previously received doxorubicin. All patients were clinically assessed for adverse reactions including skin toxicity. Results: 90 patients (mean age 62 yrs, range 45–82 yrs) were included in this analysis. There were 55 ovarian, 16 endometrial, 2 fallopian, and 17 primary peritoneal cancers. The median cumulative dose of PLD was 100 mg/m2 (range 40–855 mg/m2) with a median of 3 cycles (range 1–25). 33/90 (37%) developed a skin reaction during therapy. The overall incidence of grade 1, 2, and 3 skin toxicity was 23 (26%), 9 (10%), and 1 (1%), respectively. Of the 23 cases of grade 1 toxicity, 16 (70%) occurred within 1–3 cycles. All 9 cases of grade 2 toxicity occurred within 1–3 cycles. The only case of grade 3 toxicity occurred after the first cycle. 28/30 (93%) patients who continued treatment did not experience further episodes of skin toxicity with subsequent cycles after a dose reduction (5–20 mg/m2). PLD was stopped in only 2/90 (2%) cases due to a skin reaction. Conclusions: Severe skin toxicity (≥grade 2) associated with PLD occurs infrequently when initial doses of 40 mg/m2 are administered. When skin reactions appear, they usually occur early in the course of treatment, respond to dose reduction, and do not appear to limit the duration of treatment. No significant financial relationships to disclose.
A phase I pharmacokinetic and target validation study of the novel anti-tubulin agent E7389: A California Cancer Consortium trial
Authors: T. W. Synold, R. J. Morgan, E. M. Newman, H. J. Lenz, D. R. Gandara, A. D. Colevas, M. D. Lewis, J. H. Doroshow
Journal: Journal of Clinical Oncology (2005)

3036 Background: The California Cancer Consortium recently completed a Phase I pharmacokinetic (PK) and target validation (TV) trial of E7389. E7389, an analog of the marine compound halichondrin B, inhibits microtubule polymerization by a mechanism that is distinct from all other tubulin-binding agents. Sub- to low-nanomolar levels of E7389 inhibit cancer cell proliferation via induction of a G2/M block, disruption of mitotic spindles, and initiation of apoptosis. Methods: This first-in-man trial included a rapid titration design with real-time PK to guide dose escalation. E7389 was administered as a weekly bolus 3 weeks out of 4, starting at 0.125 mg/m2/wk. During the 1st phase, single patient (pt) cohorts were enrolled with intra- and inter-pt dose-doubling until toxicity was observed. The 2nd phase consisted of a standard 3x3 dose escalation schedule. Once the MTD was determined, a cohort of pts with biopsiable tumors was enrolled for TV studies. Results: A total of 40 (38 evaluable) pts with refractory or advanced solid tumors were entered. Median age was 61 yrs, KPS ≥ 80% in 31/38, and gender was 20/18 (M/F). Most common primary tumor sites were lung (9), breast (4), and bladder (2). Rapid escalation ended with a gr 3 alk phos at 0.5 mg/m2/wk. The 2nd phase ended at 2.0 mg/m2/wk with 2 DLT's; 1 gr 3 febrile neutropenia and 1 gr 4 neutropenia. Other serious non-heme toxicities included hypoglycemia, hypophosphatemia, and fatigue. The MTD was 1.4 mg/m2/wk. Responses included 2 PRs (NSCLC; bladder) and 3 MR (NSCLC, breast, and thyroid). SD as best response was seen in 12 pts lasting a median of 4 months (range 2–14). PK results demonstrate a tri-phasic elimination and a prolonged terminal t1/2 of 36–48 hrs. At the MTD, plasma levels of E7389 are above concentrations required for in vitro cytotoxicity for >1 week. A cohort of 13 pts was treated at the MTD and serial tumor biopsies were obtained. Fluorescent IHC analyses of these specimens demonstrate that E7389 disrupts microtubule structure in tumors in vivo Conclusions: Phase II studies of this novel, active agent are ongoing. (Sponsored by CA62505) Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eisai Eisai
Medicine and books: The Pocket Guide to Grant Applications
Authors: Nick Black
Journal: BMJ (1998)

I K Crombie, C du V Florey 

BMJ Publishing Group, £16.95, pp 88 

ISBN 0 7279 1219 4 

Doctors have traditionally received little or no formal help in learning some of the most useful and important skills that they need, such as dealing with bereavement, organising their work, management and team skills, and even some practical clinical activities. The ability to carry out research could also be included. This tradition may be peculiar to the British, with their reverence for the enthusiastic amateur, but it risks making either for poor quality research or for many disappointed and frustrated would-be researchers. 

While there are plenty of basic and advanced textbooks on how to do research, this short, concise book unashamedly addresses the most practical needs of budding health services researchers. It clearly guides the reader through all stages of preparing a project grant application, taking care to include useful advice, the need for which other authors might have failed to recognise. It even includes a disk version, which sits on screen alongside a grant application form for easy reference when writing. 

As a researcher and a member of funding bodies, I found the description of common failings in grant applications (not always confined to those received from inexperienced researchers) all too familiar. A common mistake that received insufficient attention, however, is to fail to make explicit the study design to be used or, even more worrying, to state one design and describe another. The commonest confusion seems to be between case-control and retrospective cohort studies. In this respect, it would have been helpful if the authors had made clear whether their use of “clinical trial” meant exclusively randomised trials or also included non-randomised trials (or prospective cohort studies). 

Although much health services research is quantitative, not all is. In places the authors acknowledge this and try to accommodate qualitative approaches in their general advice. This, however, was the least convincing aspect of their work—it is assumed that a sample size calculation is a requirement for all research studies and that the application of statistical techniques will always be needed. 

Apart from that, the only other things I’d take issue with were minor. Firstly, is the only problem in obtaining drug company sponsorship knowing how to apply? What about ethical considerations? Secondly, the parochial references to research funding in the United Kingdom are helpful for compatriots but will limit the book’s appeal elsewhere. And thirdly, while the authors’ call for plain English is to be applauded, their use of “methodology” for “method” irritated this reader.
Abstract IA09: Use of novel treatments for childhood ALL
Authors: Lia Gore
Journal: Cancer Research (2016)

Abstract Overall and disease free survival for childhood acute lymphoblastic leukemia (ALL) has continued to improve such that there are now subsets of patients with ALL who have a greater than 98% chance for cure, while some have significantly poorer outcomes and remain refractory to conventional treatments. Prognostic factors are refined sufficiently to allow risk-directed categorization and disease treatment allocation, which for some patients may mean less intensive therapy and the potential for fewer short- and long-term side effects, while advances in molecular and genomic diagnostics are increasingly being used to consider alterations in primary therapy for higher risk patients. Recent developments in therapies for childhood ALL such as those presented at this meeting have altered the landscape of available options for the treatment of relapsed ALL in particular, and increasingly, practicing pediatric oncologists are challenged to place these new treatments into the context of currently established therapies and prioritize the options for relapsed patients specifically. Immunotherapy and strategies using chimeric antigen T-cells, virus-specific T-cells, bi-specific antibodies (T-cell engaging and otherwise), and immunotoxins have greatly increased in availability and sophistication, and are now more widely available, with ever-increasing potential applications, although to date, they have not been applied to newly diagnosed patients. Simultaneously, the number of available new therapeutic options is large enough that meaningful clinical trials can be difficult to conduct based on the proportion of agents to the number of available patients eligible for such trials. A pressing challenge to the field is to begin to place these therapies in the context of more conventional approaches to the currently highly successful treatment of ALL for a large majority of affected patients, and to continue to evaluate both the short- and long-term consequences of newer treatments both alone and in combination with other more conventional agents. Discussion about what constitutes a truly novel therapy and examples of currently available experimental therapies for childhood ALL will be reviewed. The context of these treatments to future strategies and trial opportunities for both single agent and combination explorations will be discussed. Citation Format: Lia Gore. Use of novel treatments for childhood ALL. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Pediatric Cancer Research: From Mechanisms and Models to Treatment and Survivorship; 2015 Nov 9-12; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(5 Suppl):Abstract nr IA09.
11P Prognostic impact of MET mutations in exon 14 and copy number alterations in a series of NSCLC patients
Authors: S. Clavé, A. Dalmases, R. Longarón, L. Pijuan, D. Casadevall, Á. Taus, B. Espinet, E. Arriola, B. Bellosillo, M. Salido
Journal: Journal of Thoracic Oncology (2016)
White clot syndrome associated with renal failure.
Authors: D L Somers, C Sotolongo, J A Bertolatus
Journal: Journal of the American Society of Nephrology (1993)

In a minority of patients, heparin administration is associated with thrombocytopenia and this thrombocytopenia may be associated with thromboembolic events. Heparin-associated thromboembolism is described as heparin-associated thrombocytopenia and thrombosis or white clot syndrome. White clot syndrome is caused by antibodies to a heparin-platelet membrane complex. The diagnosis carries a high mortality and morbidity from limb thromboembolism. Treatment includes discontinuation of heparin, use of alternate anticoagulants, and aggressive treatment of thromboses. A case in which acute renal failure occurred in the setting of heparin treatment and thrombocytopenia is described, and evidence that renal failure was a result of white clot syndrome is provided.
Efficacy of BCG Vaccination in Prevention of Cancer: An Update: Brief Communication 2
Authors: Dixie E. Snider, George W. Comstock, Isidro Martinez, Gus J. Caras
Journal: JNCI Journal of the National Cancer Institute (1978)

From 1949 to 1951, a controlled trial of BCG vaccinations was conducted in Puerto Rico. The 191,827 children, 1–18 years of age, inHially enrolled in the study were skin-tested with tuberculin to determine their eligibility for vaccination. A total of 82,269 children were classified as reactors and not vaccinated. Of the 109,558 nonreactors, 31,586 refused vaccination, 50,634 were vaccinated wHh BCG, and 27,338 were left unvaccinated as controls. We ascertained the incidence of cancer over an average follow-up period of 23.3 years in the latter two groups using the Puerto Rico Central Cancer Registry. By the end of December 1973, a total of 77 cancers had been diagnosed among the controls and 150 among the vacclnees. The overall incidence of cancer among the two groups was similar. Although a number of differences existed between the vaccinee group and the controls in regard to the incidence of cancer at various "sites," none of these differences was statistically significant. However, when cases of lymphosarcoma and Hodgkin's disease were combined for analysis, a statistically significant excess of cases occurred among the vaccinees. We concluded that BCG vaccination had no protective effect on the subsequent development of cancer in this population. The slight excess of cases of lymphosarcoma and Hodgkin's disease among the vaccinees raised the possibility that BCG may have had an adverse effect.
Production of Platelet-Derived Growth Factor–like Mitogen by Smooth-Muscle Cells from Human Atheroma
Authors: Peter Libby, Stephen J.C. Warner, Robert N. Salomon, Louis K. Birinyi
Journal: New England Journal of Medicine (1988)

Proliferation of vascular smooth-muscle cells occurs during the development of atherosclerosis and the remodeling of arteries that accompanies chronic systemic or pulmonary hypertension. To help define the signals that initiate this abnormal growth, we cultured smooth-muscle cells from human atherosclerotic plaques. These cells (n = 9) released material into their culture medium that stimulated the proliferation of aortic smooth-muscle cells to a mean (±SD) level 5.1±1 times that in control medium. Part of this activity was due to molecules that resemble a mitogen first isolated from platelets and known as platelet-derived growth factor (PDGF), since these cells released PDGF measured in a radioreceptor assay (355±117 pg per milliliter per 48 hours; n = 6) and since anti-PDGF antibody neutralized 38±7 percent of this mitogenic activity (range, 13 to 60 percent; n = 6 carotid-plaque isolates). Two human genes encode distinct PDGF subunits that form dimers in different combinations to create biologically active PDGF. Cells cultured from human atheroma contained mRNAs for the PDGF A chain (16 of 17 isolates) but none (of 13) that encoded PDGF B chain (the c-sis protooncogene product). We conclude that smooth-muscle cells from diseased human arteries can secrete mitogenic activity, some of which resembles PDGF, and that these cells express the gene for the PDGF A chain selectively. This capacity to produce an endogenous, potentially self-stimulatory (autocrine) growth factor may help to explain how replication of smooth-muscle cells can begin, even while the endothelial barrier remains morphologically intact, early in atherogenesis. (N Engl J Med 1988; 318: 1493–8.)