tbuckley/cabot-search huggingface dataset:
Identification of RNA-Binding Protein LARP4B as a Tumor Suppressor in Glioma
Authors: Hideto Koso, Hungtsung Yi, Paul Sheridan, Satoru Miyano, Yasushi Ino, Tomoki Todo, Sumiko Watanabe
Journal: Cancer Research (2016)

Transposon-based insertional mutagenesis is a valuable method for conducting unbiased forward genetic screens to identify cancer genes in mice. We used this system to elucidate factors involved in the malignant transformation of neural stem cells into glioma-initiating cells. We identified an RNA-binding protein, La-related protein 4b (LARP4B), as a candidate tumor-suppressor gene in glioma. LARP4B expression was consistently decreased in human glioma stem cells and cell lines compared with normal neural stem cells. Moreover, heterozygous deletion of LARP4B was detected in nearly 80% of glioblastomas in The Cancer Genome Atlas database. LARP4B loss was also associated with low expression and poor patient survival. Overexpression of LARP4B in glioma cell lines strongly inhibited proliferation by inducing mitotic arrest and apoptosis in four of six lines as well as in two patient-derived glioma stem cell populations. The expression levels of CDKN1A and BAX were also upregulated upon LARP4B overexpression, and the growth-inhibitory effects were partially dependent on p53 (TP53) activity in cells expressing wild-type, but not mutant, p53. We further found that the La module, which is responsible for the RNA chaperone activity of LARP4B, was important for the growth-suppressive effect and was associated with BAX mRNA. Finally, LARP4B depletion in p53 and Nf1-deficient mouse primary astrocytes promoted cell proliferation and led to increased tumor size and invasiveness in xenograft and orthotopic models. These data provide strong evidence that LARP4B serves as a tumor-suppressor gene in glioma, encouraging further exploration of the RNA targets potentially involved in LARP4B-mediatd growth inhibition. Cancer Res; 76(8); 2254-64. ©2016 AACR.
Abstract 11525: Severity of Sleep-Disordered Breathing Has an Impact on the Prevalence of Nocturnal Enuresis in Patients With Cardiovascular Disease
Authors: Sunao Kojima, Takashi Miyazaki, Sayaka Noguchi, Seiji Hokimoto, Hisao Ogawa
Journal: Circulation (2013)

Backgrounds: Enuresis is an essential factor for a tumble at nighttime in hospitalized patients with advanced age. Nocturnal pulse-oxymetry is recommended as a first assessment of respiratory balan...
Molecular Profile and FDG-PET/CT Total Metabolic Tumor Volume Improve Risk Classification at Diagnosis for Patients with Diffuse Large B-Cell Lymphoma
Authors: Anne-Ségolène Cottereau, Hélène Lanic, Sylvain Mareschal, Michel Meignan, Pierre Vera, Hervé Tilly, Fabrice Jardin, Stéphanie Becker
Journal: Clinical Cancer Research (2016)

The prognostic impact of total metabolic tumor volume (TMTV) measured on pretreatment (18)F-FDG PET/CT and its added value to molecular characteristics was investigated in patients with diffuse large B-cell lymphoma (DLBCL).For 81 newly diagnosed patients with DLBCL treated with rituximab and CHOP/CHOP-like regimen, TMTV was computed using the 41% SUVmax thresholding method. According to the gene expression profile, determined using DASL (cDNA-mediated Annealing, Selection, Ligation and extension) technology, a subset of 57 patients was classified in germinal center B (GCB) or activated B-cell (ABC) subtypes and MYC or BCL2 overexpressed.Median follow-up was 64 months. Five-year progression-free survival (PFS) and overall survival (OS) were 60% and 63% in the whole population. Median pretherapy TMTV was 320 cm(3) (25th-75th percentiles 106-668 cm(3)). With a 300 cm(3) cutoff, patients with high TMTV (n = 43) had a 5-year PFS and OS of 43% and 46% compared with 76% and 78% for patients with a low TMTV (P = 0.0023, P = 0.0047). ABC status, MYC, or BCL2 overexpression and both overexpression ("dual expressor," DE) were significantly associated with a worse PFS and OS. TMTV combined with molecular data allowed a significant better risk substratification of ABC/GCB patients, on PFS and OS. High TMTV individualized in molecular-low-risk patients a group with a poor outcome (MYC, PFS=51%, OS=55% BCL2, PFS=49%, OS=49% or DE PFS=50%, OS=50%) and a group with a good outcome (MYC, PFS=93%, OS=93% BCL2, PFS=86%, OS=86%, or DE PFS=81%, OS=81%).The combination of molecular and imaging characteristics at diagnosis could lead to a more accurate selection of patients, to increase tailor therapy. Clin Cancer Res; 22(15); 3801-9. ©2016 AACR.
Systematic review of celecoxib for osteoarthritis and rheumatoid arthritis
Authors: P. Juni
Journal: BMJ (2003)

Editor—Deeks et al say that celecoxib has improved gastrointestinal safety and tolerability compared with traditional non-steroidal anti-inflammatory drugs (NSAIDs).1 We have several concerns.

Firstly, Deeks et al reported the papers by Bensen et al, Zhao et al (1999), Simon et al, and Zhao et al (2000) as if they referred to four different trials.1 The papers by Bensen et al and Zhao et al (1999) were, however, merely duplicate reports of one trial, whereas the papers by Simon et al and Zhao et al (2000) reported in duplicate on another trial. Deeks et al either included the same data more than once or mixed up unpublished data with unrelated publications.

Secondly, Deeks et al report similar relative risks for ulcer complications observed after six months in CLASS's two trials2: 0.54 (95% confidence interval 0.20 to 1.47) for study 035 (celecoxib v ibuprofen) and 0.56 (0.19 to 1.66) for study 102 (celecoxib v diclofenac), implying that it is appropriate to pool two trials by using comparator drugs of different cyclo-oxygenase-2 selectivity. According to the Food and Drug Administration (www.fda.gov), however, four events occurred in the celecoxib group and 11 in the ibuprofen group in study 035 (0.36, 0.12 to 1.14), whereas seven events occurred in the celecoxib group and nine in the diclofenac group in study 102 (0.78, 0.29 to 2.08).3 This implies that pooling these trials may be inappropriate.

Thirdly, Deeks et al's justification for considering only CLASS's six month results is problematic.4 Admittedly, data available from the FDA indicate that rates of patient withdrawal were different in the celecoxib and ibuprofen groups, implying that results for study 035 were unreliable at all time points. In accordance with Deeks et al, this trial should therefore have been excluded from all analyses. Contrary to Deeks et al, however, no relevant differences were found between celecoxib and diclofenac groups in study 102. The differences in duration of treatment between the celecoxib and diclofenac groups reported by Deeks et al merely relate to the fact that for half of the patients taking celecoxib (study 035) the maximum duration of treatment was 15 months, whereas for patients allocated to diclofenac in study 102 the maximum duration of treatment was only 12 months. 4

Fourthly, patients with osteoarthritis or rheumatoid arthritis generally take NSAIDs for years. Therefore, Deeks et al's short term results are misleading. There is no evidence that in the long term celecoxib is more beneficial than diclofenac in avoiding severe gastrointestinal complications (relative risk for CLASS's complete follow up 1.10, 0.47 to 2.58).3
Erucism Due to Lepidoptera Caterpillar Envenomation
Authors: Robert N E French, Daniel Brillhart
Journal: New England Journal of Medicine (2015)

A 42-year-old woman contacted the Arizona poison center after envenomation by a tricolor buckmoth caterpillar. She had been underneath a mesquite tree when the caterpillar fell onto her left shoulder. Within minutes, a pruritic urticarial eruption had developed.
Duration of Bronchial Squamous Metaplasia Produced in Dogs by Cigarette Smoke Condensate&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Dale L. Tipton, M.D., T. Timothy Crocker, M.D.
Journal: JNCI Journal of the National Cancer Institute (1964)

Cigarette smoke condensate, 0.05 to 0.1 ml, was applied on the left mainstem bronchus of dogs daily, for 8 days, by bronchoscopy. Biopsy 3 days later demonstrated that all animals had developed squamous metaplasia of respiratory mucosa. Two dogs were autopsied at intervals of 3 days, 5, 9, 11, 14, and 18 weeks after the last tar application. Tissue blocks were taken from the trachea down to the lobar bronchi in an unbroken series so that this entire area could be scanned histologically. At 3 days, squamous metaplasia extended from the terminal trachea into the left mainstem bronchus with some spread to the right side. By 5 weeks, the squamous metaplasia had declined as the major abnormality, and a transitional type of epithelium was most prominent. At 9 weeks normal, transitional, and hyperplastic epithelium occurred in equal frequency. Hyperplasia predominated at 11 weeks, though the transitional state persisted in some areas. At 14 weeks, hyperplastic zones occurred at peak frequency alternating with normal epithelium. By 18 weeks essentially all epithelium was normal. These results demonstrate that squamous metaplasia can be induced rapidly in dogs by cigarette smoke condensate. Reversal occurred in a sequence of abnormal epithelial states of differentiation which, though progressively more normal, did not reach normal until several divisions of basal cells were presumed to have occurred. The suggestion is made that abnormal differentiation persisting through several cell generations in the absence of further irritant identifies basal cells as the probable site of action of the tar and indicates that these cells were so altered as to produce daughter cells which failed to differentiate normally.
Erythema Dyschromicum Perstans Response to Isotretinoin
Authors: Fang Wang, Yu-Kun Zhao, Zhuo Wang, Juan-Hua Liu, Di-Qing Luo
Journal: JAMA Dermatology (2016)

of cutaneous cancers; the addition of voriconazole appears to accelerate UV-induced skin damage. 5While our patient had been on a long-term treatment regimen of low-dose corticosteroids, she was relatively immunocompetent, suggesting that immunocompetent individuals may also be at risk for photocarcinogenic effects of voriconazole. 6 Posaconazole appears to have a more favorable adverse effect profile than voriconazole. 3 In a case series of 3 patients with voriconazole-associated SCC, posaconazole was replaced in 2 of 3 patients, with improvement of the photosensitivity reaction. 6 While the present patient did not cease developing SCCs, tumor burden and quality of life improved.Considering that posaconazole has a favorable adverse effect profile, it should be considered more often for patients who are at risk of cutaneous cancer development.
Frequency of and risk factors for the surgical resection of nonmalignant colorectal polyps: a population-based study
Authors: Florence Le Roy, Sylvain Manfredi, Stéphanie Hamonic, Christine Piette, Guillaume Bouguen, Françoise Riou, Jean-François Bretagne
Journal: Endoscopy (2015)

<b>Background and study aims: </b>The management of patients with colon polyps who are referred to surgery remains uncharacterized in a population-based setting. The aims of this study were to determine the frequency, risk factors, and outcomes of patients referred for surgical resection of colorectal polyps. <b>Patients and methods: </b>All patients who underwent a colonoscopy for positive fecal occult blood test in the setting of a population-based colorectal cancer screening program in France between 2003 and 2012 were analyzed. The primary outcome was the proportion of patients undergoing colorectal surgery for polyps without invasive carcinoma. Logistic regression analysis was applied to identify risk factors for surgical resection. <b>Results: </b>Among 4251 patients with at least one colorectal polyp, 175 (4.1 %) underwent colorectal surgery. Risk factors for surgery included size, proximal polyp location, advanced histology (villous or high grade dysplasia), the endoscopy center, and colonoscopy performed during the first half of the study period. Subgroup analysis of 3475 colonoscopies performed by 22 endoscopists who performed at least 50 colonoscopies during the study period, identified the endoscopist as an additional risk factor. The adjusted proportions of referrals to surgery ranged from 0 to 46.6 % per endoscopist for polyps ≥ 20 mm (median 20.2 %). Overall, surgical complications occurred in 24.0 %, and one patient died following surgery (0.5 %). None of the 175 patients who underwent surgery were referred to a tertiary endoscopic center prior to surgery. <b>Conclusions: </b>In this population-based study, 4.1 % of patients with nonmalignant polyps were referred for surgical resection. The endoscopist was one important factor that was associated with surgical referral. To further decrease the proportion of inappropriate surgery in patients, endoscopists should refer their patients with large or difficult polyps to expert endoscopists prior to surgery.
A longitudinal study about lung function and symptoms in patients with pollution-related illness
Authors: Takako Tanaka, Masaharu Asai, Hideaki Senjyu
Journal: European Respiratory Journal (2012)

Background:  Air pollution is known a leading cause of respiratory symptoms. In Japan, an improvement of the atmosphere was achieved by the pollution organic act, and patients with air pollution-related illness have received medical care for more than 20 years under the Pollution Compensation Law.   Objectives:  This study was to verify the effects of Japan system by investigating the long-term consequences of exposure to air pollution on lung function and symptoms in patients with pollution-related illness.   Methods:  The study included 782 surviving patients with pollution-related illness in Okayama who were ≥ 65 years of age in 2009. The patients had all received medical care, including expectorants and bronchodilators, once or twice a month and had undergone spirometry and assessment of respiratory symptoms each year for more than twenty years. We analyzed lung function and symptoms from 2000-09.   Results:  Almost all (male: 59.0%, female: 78.6%) of the subjects had normal pulmonary function. However, a high proportion of subjects reported respiratory symptoms. All measures of pulmonary function decreased. The annual mean change of the VC was -40.5 ml/y (male) and -32.7 ml/y (female). The change in the FEV 1  was -27.6 ml/y (male) and -23.9ml/y (female). In addition, there was a significant (male: p   Conclusions:  The annual mean changes of lung function were within the normal ranges. The findings suggested that the medical care compensation system in Japan is effective. Although in order to reduce dyspnea, we believe that it is necessary for patients with pollution-related illness to also receive respiratory rehabilitation.
Concurrent Genetic Alterations in Lung Cancer: a Comprehensive Genomic Profiling in a Japanese Cohort
Authors: T. Taira, H. Kenmotsu, M. Serizawa, K. Wakuda, H. Akamatsu, T. Shukuya, A. Ono, H. Imai, T. Naito, H. Murakami, M. Endo, T. Nakajima, Y. Ohde, N. Yamamoto, Y. Koh, T. Takahashi
Journal: Annals of Oncology (2014)
Clinical presentation pattern is more closely associated with treatment outcome than histologic subtypes in Castleman’s disease
Authors: Y. S. Hong, Y. H. Park, D. W. Kim, S. A. Im, T. Y. Kim, S. S. Yoon, D. S. Heo, Y. J. Bang, S. Park, N. K. Kim
Journal: Journal of Clinical Oncology (2005)

6635 Background: Three histologic variants (hyaline vascular, plasma-cell, and mixed) and two clinical types (localized and multicentric) of Castleman’s disease have been described. However, it is not known whether there is any correlation between histologic and clinical types. To evaluate prognostic implication of subtyping, treatment outcome was evaluated based on histologic and clinical types. Methods: 42 patients with histologically confirmed Castleman’s disease were studied between Jun 1994 and Apr 2004. Patients were identified as having localized or multicentric disease, and further divided as histology. The endpoint was patient death. Results: Of the 42 patients, 27 patients had localized disease and 15 patients had multicentric disease. 18 patients of the localized disease had histology of hyaline vascular type and 8 patients of the multicentric disease had histology of plasma-cell type (p=0.006). Most frequent involved site was neck in localized disease and abdomen in multicentric disease. All of 27 patients with localized disease underwent surgical excision and all remain free of disease for median follow up duration of 55 months (range 1–124 months). 6 patients in multicentric disease were associated with POEMS syndrome, but none in localized disease (p=0.001). 13 patients with multicentric disease treated with steroids and 1 patient with combination chemotherapy. Of 13 patients treated initially with steroids, 4 patents showed clinical improvements, 9 patients showed refractoriness or progression. 1 patient treated with combination chemotherapy showed complete remission for 16 months. 5 year survival rates for localized disease and multicentric disease were 100% and 40.6% respectively (p<0.001). There was no survival difference among histologic variants in multicentric disease (p=0.319). Causes of deaths might be due to immunologic dysfunction of unknown causes, rather than neoplastic progression. Conclusions: Clinical presentation pattern is more closely associated with treatment outcome than histologic subtypes in Castleman’s disease. Localized disease could be controlled by surgery alone, but multicentric disease showed poor prognosis. No significant financial relationships to disclose.
Pseudoaneurysm of the pulmonary artery with massive haemoptysis due to an invasive pulmonary mucormycosis
Authors: Alberto Lopez-Pastorini, Aris Koryllos, Michael Brockmann, Wolfram Windisch, Erich Stoelben
Journal: Thorax (2015)

A 62-year-old man diagnosed with glioblastoma multiforme and currently under chemoradiation therapy presented with massive haemoptysis. Chest computed tomographic scan disclosed a round-shaped formation in the right upper lobe with contrast agent leakage indicating …
How well do we communicate with patients concerning adjuvant systemic therapy? A survey of 150 colorectal cancer survivors
Authors: N. Love, C. Bylund, N. J. Meropol, J. L. Marshall, S. A. Curley, L. M. Ellis, A. Grothey, H. J. Lenz, L. B. Saltz, M. A. Elder
Journal: Journal of Clinical Oncology (2007)

4020 Background: Adjuvant chemotherapy (AC) presents a substantial patient education challenge to medical oncologists (MOs). Findings from our 2005 pilot survey suggest that a significant fraction of colorectal cancer (CRC) survivors are willing to undergo AC for modest treatment benefits, but their understanding of risks and benefits may be suboptimal. This project attempted to validate these findings by surveying patients with CRC (Pts) who previously received AC. Methods: 150 Pts who received AC for CRC in the last 5 years were recruited to listen to an audio program on AC featuring interviews with clinical investigators (CIs) and Pts who received AC. Based on this input, Pts were asked whether they would undergo the same AC again for varying absolute treatment benefits. A corresponding survey asked 24 CRC CIs and 150 MOs to predict how patients would respond. The survey also queried Pts about their expectations of and experiences with AC side effects. Results: About 1/3 of Pts would be treated again with AC for a 1% absolute reduction in recurrence risk (ARRR), and about 2/3 believed a 5% ARRR would justify treatment. There were no statistically significant differences between responses of males and females or between Pts receiving oxaliplatin (OX) and those receiving other regimens. ( Table 1 ) The corresponding estimates of CIs and MOs were lower. Additionally, AC side effects were different than expected: 57% and 66% of Pts experienced less GI toxicity and alopecia, respectively, while 38% and 46% of Pts receiving OX experienced greater cold intolerance and numbness. Conclusions: Many potential obstacles exist in communicating with Pts about AC including heterogeneity in Pts’ attitudes towards risk/benefit trade-offs and preconceptions about treatment side effects. The next step in this initiative will be to examine these issues prospectively by evaluating the impact of an audio/web education supplement on the decision-making process. [Table: see text] No significant financial relationships to disclose.
Evidence of benefit of personal budgets is outdated, says spending watchdog
Authors: Matthew Limb
Journal: BMJ (2016)

The Department of Health for England should collect better data to understand how personal budgets and direct payments benefit people, the National Audit Office (NAO) has said.

The spending watchdog said that much of the positive evidence for “personalised commissioning” was old or related to subgroups of users and that current monitoring couldn’t fully explain the effect of personal budgets on outcomes.

Another concern was how financially hardpressed local authorities were expected to save money by using personal budgets for adult social care.

“It is not clear whether local authorities will achieve the spending reductions they have forecast without putting user outcomes at risk,” said the NAO in a report on personalised commissioning in adult social care published on 3 March.1

It …
Registry of Experimental Cancers of the National Cancer Institute
Authors: Harold L. Stewart, Thelma B. Dunn, John H. Schneider, Margaret K. Deringer
Journal: JNCI Journal of the National Cancer Institute (1976)

This report describes the organization and functions of the Registry of Experimental Cancers and gives the chronology of events that led to its establishment. Currently 21,500 accessions have been coded; the vast majority are spontaneous and induced cancers, chiefly of rodents, and also a wide variety of nonneoplastic diseases. Accessions are accepted from contributors working in laboratories in this country and abroad. The material is available for study by responsible scientists, and a limited number of study sets is available for loan on request.
Drunk on risk: how the chief medical officers’ alcohol guidelines are demonising drink
Authors: David M Shaw
Journal: BMJ (2016)

Marteau praises the new alcohol guidelines,1 2 but they send a mixed message that miscommunicates the risks of drinking to the public. Except for the strong willed minority who will quit drinking entirely, the warning that “no alcohol is safe” will probably be counterproductive, as people might be happy to cut down but not to eliminate alcohol completely.3 In addition, …
Tobacco mosaic virus-based protein nanoparticles and nanorods for chemotherapy delivery targeting breast cancer
Authors: Michael A. Bruckman, Anna E. Czapar, Allen VanMeter, Lauren N. Randolph, Nicole F. Steinmetz
Journal: Journal of Controlled Release (2016)

Drug delivery systems are required for drug targeting to avoid adverse effects associated with chemotherapy treatment regimes. Our approach is focused on the study and development of plant virus-based materials as drug delivery systems; specifically, this work focuses on the tobacco mosaic virus (TMV). Native TMV forms a hollow, high aspect-ratio nanotube measuring 300 × 18 nm with a 4 nm-wide central channel. Heat-transformation can be applied to TMV yielding spherical nanoparticles (SNPs) measuring ~ 50 nm in size. While bioconjugate chemistries have been established to modify the TMV rod, such methods have not yet been described for the SNP platform. In this work, we probed the reactivity of SNPs toward bioconjugate reactions targeting lysine, glutamine/aspartic acid, and cysteine residues. We demonstrate functionalization of SNPs using these chemistries yielding efficient payload conjugation. In addition to covalent labeling techniques, we developed encapsulation techniques, where the cargo is loaded into the SNP during heat-transition from rod-to-sphere. Finally, we developed TMV and SNP formulations loaded with the chemotherapeutic doxorubicin, and we demonstrate the application of TMV rods and spheres for chemotherapy delivery targeting breast cancer.