tbuckley/cabot-search huggingface dataset:
Abstract 2302: Analysis of the role of CADM1 in suppression of lung cancer using Cadm1-deficient mice
Authors: Takeshi Ito, Masayoshi Nagata, Taketo Kawai, Mika Sakurai-Yageta, Akihiko Ito, Akiteru Goto, Daisuke Matsubara, Yoshinori Murakami
Journal: Cancer Research (2015)

Abstract Lung cancer is the leading cause of cancer deaths, and non-small-cell lung cancer (NSCLC) is the most prevalent form of lung cancer. The tumor suppressor gene CADM1/TSLC1 was originally identified in NSCLC. CADM1 encodes an immunoglobulin superfamily cell adhesion molecule. CADM1 is inactivated by deletion and/or promoter methylation of the gene in 40-60% of NSCLC, especially in their advanced stages. Previously we generated conventional Cadm1-deficient mice and found that around 40% of Cadm1-deficient mice spontaneously developed lung adenoma and adenocarcinoma by 15 months of age. To assess the precise role of CADM1 in suppression of lung tumorigenesis, we crossed Cadm1-deficient mice to conditional K-ras-mutant mice, well-established mouse models of lung cancer. The K-ras-mutant mice are shown to develop multiple lung adenocarcinomas by 25 weeks after administration of adenovirus expressing Cre recombinase followed by the activation of oncogenic K-ras. We then analyzed the development of lung tumors in K-ras-mutant (K) mice and K-ras-mutant Cadm1-deficient (KC) mice. Loss of Cadm1 results in enlargement of the size of alveolar tumors (adenomas or adenocarcinomas) as well as higher tumor grades. The most malignant histology of vascular or pleural invasion was only detected in tumors from KC mice. On the other hand, the size of the bronchial tumors was larger in K mice than in KC mice. Immunohistochemical analysis of bronchial marker SOX2 showed that adenomas or adenocarcinomas expressing SOX2 were larger in KC mice, indicating that loss of Cadm1 enhanced the rapid growth of alveolar tumors and thereby impaired the growth of bronchial tumors originated from the common stem cells, bronchio-alveolar stem cells (BASCs). Furthermore, tumors from K mice showed frequent loss of CADM1 expression and the tumors with low expression of CADM1 exhibited more malignant histological features. These results suggest that loss of Cadm1 promotes the malignant progression of alveolar tumor. Citation Format: Takeshi Ito, Masayoshi Nagata, Taketo Kawai, Mika Sakurai-Yageta, Akihiko Ito, Akiteru Goto, Daisuke Matsubara, Yoshinori Murakami. Analysis of the role of CADM1 in suppression of lung cancer using Cadm1-deficient mice. [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 2302. doi:10.1158/1538-7445.AM2015-2302
From BLISS to ILLUMINATE studies: “Blys repetita placent”?: Table 1
Authors: Laurent Chiche, Noémie Jourde-Chiche, Frederique Retornaz, Divi Cornec
Journal: Annals of the Rheumatic Diseases (2015)

Although disappointing, the results of the ILLUMINATE trials are read with great attention.1 ,2 These trials assessed the efficacy of tabalumab, a B lymphocyte stimulator (Blys) inhibitor, in systemic lupus erythematosus (SLE). Unfortunately, the results were not considered by Lilly worth following the development of this new agent, of the same therapeutic class than belimumab, the first biologic to be labelled in SLE.3 ,4 Overall, what retained our attention were the similarities between designs and results of ILLUMINATE and BLISS studies, while the fates of the two corresponding drugs were so different (table 1).

View this table:

Table 1 
Phase III studies conducted in non-renal patients with SLE targeting Blys



Indeed, apart from slight differences in the design concerning the management of standard of care treatments, the inclusion of patients from different countries and the choice of a different cut-off for the outcome criteria, these four studies addressed large populations of patients with SLE with similar characteristics that were evaluated with the same composite outcome measure SLE Responder Index5 and showed only a modest (around 10%) response rate difference between active treatment and placebo. Notably, there were differences between the two ILLUMINATE studies as observed between the two BLISS studies (table 1). A significant …
Phase II trial of chemotherapy alone for primary CNS and intraocular lymphoma.
Authors: V Sandor, V Stark-Vancs, D Pearson, R Nussenblat, S M Whitcup, P Brouwers, N Patronas, J Heiss, E Jaffe, M deSmet, D Kohler, R Simon, R Wittes
Journal: Journal of Clinical Oncology (1998)

PURPOSE Primary CNS lymphoma (PCNSL) and primary intraocular lymphoma (IOL) are usually treated with radiation therapy alone or in combination with chemotherapy. The neurotoxicity of these treatments can be substantial. This study attempts to define the toxicity and efficacy of the treatment of this disease with chemotherapy alone. PATIENTS AND METHODS Fourteen nonimmunocompromised patients were accrued to a chemotherapy regimen that incorporated a 24-hour infusion of high-dose methotrexate total dose of 8.4 g/m2 with leucovorin rescue; thiotepa 35 mg/m2; vincristine 1.4 mg/m2; dexamethasone; and intrathecal cytarabine (Ara-C) and methotrexate (MTV) administered in 21-day cycles. Seven patients were prospectively followed up with formal neuropsychologic assessments for evidence of CNS toxicity. RESULTS The response rate was 100% with 11 (79%) complete responses and three (21%) partial responses. Cumulative survival and progression-free survival rates at more than 4.5 years were 68.8% and 34.3%, respectively. Median survival has not been reached, and median progression-free survival was 16.5 months. Toxicity included severe leukoencephalopathy that was clearly attributable to chemotherapy (two patients), grade 3 or 4 neutropenia in 50% of the cycles administered, ileus (one patient), and seizures (two patients). Mucositis and renal and hepatic toxicity were mild and not therapy limiting. CONCLUSION The MTV regimen is generally well tolerated and produces a high complete response rate. Chemotherapy alone should be investigated further in this disease to assess the necessity of initial radiation therapy, either alone or in combined modality regimens, for the achievement of optimal response and survival.
The Role of Craving in Substance Use Disorders: Theoretical and Methodological Issues
Authors: Michael A. Sayette
Journal: Annual Review of Clinical Psychology (2015)

Craving is a central feature of addiction. Its recent inclusion as a diagnostic criterion for substance use disorders in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders appears at a time when craving research is at an all-time high. Craving is thought to predict relapse and may deter individuals from even trying to quit. Researchers have developed experimental craving-induction paradigms to identify factors contributing to craving and to test interventions to alleviate craving. This review offers a critique of laboratory craving studies, with particular emphasis on cigarette craving. It raises questions concerning several conceptual and methodological assumptions underlying this research, identifies processes that may explain why cravings are linked to drug use and relapse, addresses contextual factors that may influence various experiences of craving, and considers recent interventions targeting craving. The relation between craving and both emotion and coping is discussed, as well as the level of insight that individuals have about their own future cravings.
A unique monoclonal antibody for therapeutic use against chronic hepatitis B: not all antibodies are created equal
Authors: Camille Sureau
Journal: Gut (2015)

Even though current antiviral treatments based on pegylated interferon, or nucleos(t)ide analogues, in mono or combination therapies, have demonstrated clinical benefit to HBV-infected patients, chronic hepatitis B remains a difficult-to-cure disease. An absolute cure, defined as total elimination of HBV DNA, is currently not achievable, and a functional cure characterised by sustained virological response and HBV surface antigen (HBsAg) clearance off-treatment remains a challenge. Pegylated interferon treatment can lead to a sustained virological response and HBsAg clearance off-treatment in only 3–7% of patients,1 and it is too often associated with contraindications and adverse effects. Long-term treatment with nucleos(t)ide analogues is better tolerated, but the chance to achieve a sustained virological response and HBsAg loss remains low,2 and the drugs do not eradicate intrahepatic HBV DNA.

The risk of disease progression and development of hepatocellular carcinoma in chronically HBV-infected patients is clearly associated with high levels of serum HBV DNA and HBsAg.3 ,4 Since high levels of serum HBsAg may be responsible for exhaustion of HBsAg-specific T-cell response in chronically infected individuals, an antiviral strategy aimed at suppressing circulating HBsAg could restore virus-specific immune response and promote viral clearance.5

Zhang et al 6 investigated the potential of anti-HBsAg monoclonal antibodies (mAbs) infusion for clearance of circulating HBsAg in chronic infection. The study was based on (i) the previous observation that anti-HBsAg mAbs treatments could have short-term antiviral effects,7 ,8 and (ii) the growing interest in mAbs-based immunotherapy for viral diseases, including infections with HIV, HCV and Ebola virus.9 The therapeutic use of antiviral mAbs was initially based on the mAbs activity in virus neutralisation …
Effect of body surface decolonisation on bacteriuria and candiduria in intensive care units: an analysis of a cluster-randomised trial
Authors: Susan S Huang, Edward Septimus, Mary K Hayden, Ken Kleinman, Jessica Sturtevant, Taliser R Avery, Julia Moody, Jason Hickok, Julie Lankiewicz, Adrijana Gombosev, Rebecca E Kaganov, Katherine Haffenreffer, John A Jernigan, Jonathan B Perlin, Richard Platt, Robert A Weinstein
Journal: The Lancet Infectious Diseases (2015)
The current state of respiratory research in the UK
Authors: Noel Snell, Ian Jarrold, Stephen Holgate
Journal: Thorax (2015)

In 1985, Malcolm (now Sir Malcolm) Green wrote a Thorax editorial bemoaning the lack of funding for research into respiratory diseases in the UK and announcing the launch of a new charity devoted to raising funds specifically for respiratory research—the British Lung Foundation (BLF).1 Subsequent reviews from the BLF and other perspectives reaffirmed the theme of relative underfunding for research in respiratory disorders compared with other disease areas with a comparable disease burden.2–4 As the BLF celebrates its 30th anniversary this year, it seems an appropriate time to take stock of the current situation.

Figure 1 is derived from data generated by the UK Clinical Research Collaboration.5 It shows very clearly the marked disparity in research spending on respiratory disorders compared with other comparable disease areas, both in absolute terms and also, more tellingly, in relation to disease burden as measured by WHO disability-adjusted life-year rates in the UK. There is little real change in the relative spends between 2004–2005 and 2009–2010. A third report is due to be published later this year; we await the updated figures with interest.



Figure 1 
Comparison of proportion of combined spend on health-specific categories with WHO DALY rates. Data taken from ref. 5, with permission. DALY, disability-adjusted life-year.



We have attempted to obtain figures for recent spending on UK respiratory research by government agencies (the Medical Research Council, MRC; and National Institute for Health Research, NIHR) and relevant major charities (see table 1). The annual research spend by each body is the most recent full-year figure obtainable from publicly-available annual reports (financial years and reporting periods differ between the various bodies; hence, the period covered lies between 2012 and 2015).

View this table:

Table 1 
Annual spend on respiratory research by major government agencies and charities



It can be seen that …
Genome Editing: A New Approach to Human Therapeutics
Authors: Matthew Porteus
Journal: The Annual Review of Pharmacology and Toxicology (2015)

The ability to manipulate the genome with precise spatial and nucleotide resolution (genome editing) has been a powerful research tool. In the past decade, the tools and expertise for using genome editing in human somatic cells and pluripotent cells have increased to such an extent that the approach is now being developed widely as a strategy to treat human disease. The fundamental process depends on creating a site-specific DNA double-strand break (DSB) in the genome and then allowing the cell's endogenous DSB repair machinery to fix the break such that precise nucleotide changes are made to the DNA sequence. With the development and discovery of several different nuclease platforms and increasing knowledge of the parameters affecting different genome editing outcomes, genome editing frequencies now reach therapeutic relevance for a wide variety of diseases. Moreover, there is a series of complementary approaches to assessing the safety and toxicity of any genome editing process, irrespective of the underlying nuclease used. Finally, the development of genome editing has raised the issue of whether it should be used to engineer the human germline. Although such an approach could clearly prevent the birth of people with devastating and destructive genetic diseases, questions remain about whether human society is morally responsible enough to use this tool.
Advances in Functional Assemblies for Regenerative Medicine
Authors: Matteo Palma, John G. Hardy, Ghazal Tadayyon, Maria Farsari, Shalom J. Wind, Manus J. Biggs
Journal: Advanced Healthcare Materials (2015)

The ability to synthesise bioresponsive systems and selectively active biochemistries using polymer-based materials with supramolecular features has led to a surge in research interest directed towards their development as next generation biomaterials for drug delivery, medical device design and tissue engineering.
Amenorrhoea need not be an end point
Authors: D T Y Liu
Journal: BMJ (1995)

after extensive division of ahesions she was found to have moderate diverticular disease of the sigmoid colon with a loop stuck to the left posterolateral aspect of the uterus forming the fistulous communication.Given the degree of adhesions and the anatomy, she underwent a subtotal hysterectomy and oversewing of the colonic defect.Apart from a minor wound infection the remainder of her recovery was uneventful.Presumably the fistula resulted from trauma arising from the conduction of diathermy current during the endometrial ablation.While the introduction of minimally invasive but equiefficacious hysteroscopic techniques should be encouraged, serious complications may still arise.
Heightening Energetic Stress Selectively Targets LKB1-Deficient Non–Small Cell Lung Cancers
Authors: Milica Momcilovic, Robert McMickle, Evan Abt, Atsuko Seki, Sarah A. Simko, Clara Magyar, David B. Stout, Michael C. Fishbein, Tonya C. Walser, Steven M. Dubinett, David B. Shackelford
Journal: Cancer Research (2015)

Abstract Inactivation of the LKB1 tumor suppressor is a frequent event in non–small cell lung carcinoma (NSCLC) leading to the activation of mTOR complex 1 (mTORC1) and sensitivity to the metabolic stress inducer phenformin. In this study, we explored the combinatorial use of phenformin with the mTOR catalytic kinase inhibitor MLN0128 as a treatment strategy for NSCLC bearing comutations in the LKB1 and KRAS genes. NSCLC is a genetically and pathologically heterogeneous disease, giving rise to lung tumors of varying histologies that include adenocarcinomas and squamous cell carcinomas (SCC). We demonstrate that phenformin in combination with MLN0128 induced a significant therapeutic response in KRAS/LKB1–mutant human cell lines and genetically engineered mouse models of NSCLC that develop both adenocarcinomas and SCCs. Specifically, we found that KRAS/LKB1–mutant lung adenocarcinomas responded strongly to phenformin + MLN0128 treatment, but the response of SCCs to single or combined treatment with MLN0128 was more attenuated due to acquired resistance to mTOR inhibition through modulation of the AKT-GSK signaling axis. Combinatorial use of the mTOR inhibitor and AKT inhibitor MK2206 robustly inhibited the growth and viability of squamous lung tumors, thus providing an effective strategy to overcome resistance. Taken together, our findings define new personalized therapeutic strategies that may be rapidly translated into clinical use for the treatment of KRAS/LKB1–mutant adenocarcinomas and squamous cell tumors. Cancer Res; 75(22); 4910–22. ©2015 AACR.
Infections in Child Day Care Centers as they Relate to Internal Medicine
Authors: Randall R. Reves, Larry K. Pickering
Journal: Annual Review of Medicine (1990)

Internists should be aware of the increased frequency of most communicable diseases among parents and child care providers exposed to children attending child day care centers. Episodes of shigellosis and hepatitis A among adults in contact with children in day care centers should be promptly reported to public health authorities, since they may indicate the presence of a day care center outbreak for which effective control measures are available. Although effective treatment or intervention is limited or not available for many other infections acquired by adults from children in day care centers, significant illness may result in a minority of individuals at increased risk for infection with agents such as cytomegalovirus and varicella. Acute infectious diseases of children caused by organisms transmitted from day care center staff are less common and largely preventable by ensuring that staff are appropriately immunized and screened for tuberculosis.
Defining remission and treatment success using the DAPSA score: response to letter by Helliwell and Coates
Authors: Monika M Schoels, Daniel Aletaha, Josef S Smolen
Journal: Annals of the Rheumatic Diseases (2015)

We truly appreciate the comments on our study of Disease Activity Index for Psoriatic Arthritis (DAPSA) disease activity states and DAPSA responses provided by Drs. Helliwell and Coates,1 because this gives us a dual opportunity: first, to address the principal differences in our thinking on psoriatic arthritis (PsA) compared with that of the authors of the letter, and second to expand on our findings. The authors, whose work we have followed and valued highly for many years, present a large number of comments that we will try to answer individually. 

1.  Concerns about only assessing joints. The authors ought to take notice that the DAPSA is not solely comprised of joint counts, but, aside from C-reactive protein (CRP), also includes patient global assessment (PtGA) as well as patient pain assessment (PtP).

2.  Cut-offs were developed based entirely on physician opinion without including patients. While we sent our survey only to physicians, it needs to be borne in mind that the DAPSA includes PtGA and PtP and thus is already heavily weighted with the views of the patient. This item is again mentioned as being ‘disappointing’ toward the end of the letter. However, we were partly inspired by the authors themselves who stated in their publication on the definition of moderate disease activity (MDA) that the “questionnaire … was then circulated to rheumatologists and dermatologists with an interest in PsA, identified through membership of GRAPPA”,2 without involving patients. To us it seemed preferable to obtain the patients‘ opinions on cut points and responses in a separate currently evolving activity. This will enable involving a large number of patients, rather than adding a few patients to the survey as suggested by the authors.

3.  Response criteria used randomised controlled trial (RCT) datasets rather than data from the PsA population as a whole. In …
Post-Translational Modification of CCL23 in Chronic Rhinosinusitis with Nasal Polyps
Authors: Anjeni Keswani, Julie Poposki, Sarah Peterson, Lydia Suh, James Norton, Anju Peters, Leslie C. Grammer, Bruce Tan, Rakesh Chandra, David Conley, Juan Jaen, Thomas Schall, Robert Kern, Robert P. Schleimer, Atsushi Kato
Journal: Journal of Allergy and Clinical Immunology (2013)
Leptin, BMI, and a Metabolic Gene Expression Signature Associated with Clinical Outcome to VEGF Inhibition in Colorectal Cancer
Authors: Aurélien J.C. Pommier, Matthew Farren, Bhavika Patel, Mark Wappett, Filippos Michopoulos, Neil R. Smith, Jane Kendrew, Jeremy Frith, Russell Huby, Catherine Eberlein, Hayley Campbell, Christopher Womack, Paul D. Smith, Jane Robertson, Shethah Morgan, Susan E. Critchlow, Simon T. Barry
Journal: Cell Metabolism (2015)
Multiparametric prostate magnetic resonance imaging in the evaluation of prostate cancer
Authors: Baris Turkbey, Anna M. Brown, Sandeep Sankineni, Bradford J. Wood, Peter A. Pinto, Peter L. Choyke
Journal: CA A Cancer Journal for Clinicians (2015)

Imaging has traditionally played a minor role in the diagnosis and staging of prostate cancer. However, recent controversies generated by the use of prostate‐specific antigen (PSA) screening followed by random biopsy have encouraged the development of new imaging methods for prostate cancer. Multiparametric magnetic resonance imaging (mpMRI) has emerged as the imaging method best able to detect clinically significant prostate cancers and to guide biopsies. Here, the authors explain what mpMRI is and how it is used clinically, especially with regard to high‐risk populations, and we discuss the impact of mpMRI on treatment decisions for men with prostate cancer. CA Cancer J Clin 2016;66:326‐336. © 2015 American Cancer Society
Resection rate of lung cancer in Teesside (UK) and Varese (Italy): a comparison after implementation of the National Cancer Plan
Authors: Andrea Imperatori, Richard N Harrison, Lorenzo Dominioni, Neil Leitch, Elisa Nardecchia, Vandana Jeebun, Jacqueline Brown, Elena Altieri, Massimo Castiglioni, Maria Cattoni, Nicola Rotolo
Journal: Thorax (2015)

<h3>Background</h3> In a lung cancer survey in 2000 we showed significantly less favourable stage distribution and lower resection rate in Teesside (UK) than in the comparable industrialised area of Varese (Italy). Lung cancer services in Teesside were subsequently reorganised according to National Cancer Plan recommendations. <h3>Methods</h3> For all new lung cancer cases diagnosed in Teesside (n=324) and Varese (n=260) during the 12 months October 2010 to September 2011 (hereafter ‘the 2010 cohort’), demographic, clinico-pathological and disease management data were prospectively recorded using the same database and protocol as the 2000 survey. Findings were analysed focusing on resection rate. <h3>Results</h3> In the 2010 cohort compared with 2000, both in Teesside and Varese emergency referral decreased (p&lt;0.001), performance status improved (p&lt;0.001), but cancer stage shift was not seen; resection rate improved in Teesside, from 7% to 11% (p=0.054), and was unchanged in Varese (24%). Moreover, in Teesside compared with Varese the stage distribution remained less favourable, stage I–II non-small cell lung cancer (NSCLC) proportion being respectively 12% and 19% (p=0.040), and resection rate in all lung cancers remained lower (11% and 24%; p&lt;0.001). On multivariate analysis, resection predictors in Teesside were as follows: stage I–II NSCLC (OR 86.14; 95% CI 31.80 to 233.37), performance status 0–1 (OR 5.02; 95% CI 1.48 to 17.07), belonging to 2010 cohort (OR 2.85; 95% CI 1.06 to 7.64). <h3>Conclusions</h3> In Teesside the main independent predictor of resection was disease stage; in 2010–2011 compared with 2000, lung cancer service improved but stage shift did not occur, and resection rate increased but remained significantly lower than in Varese.