tbuckley/cabot-search huggingface dataset:
Abstract 1681: Iron chelation therapy increased the anticancer effect of sorafenib in hepatocarcinoma
Authors: Shinichi Urano, Toshiaki Ohara, Ryoichi Katsube, Shinichiro Watanabe, Kazuhiro Noma, Yasuko Tomono, Hiroshi Tazawa, Kazuhiro Nouso, Yasuhiro Shirakawa, Toshiyoshi Fujiwara
Journal: Cancer Research (2014)

Abstract [Purpose] Iron overload is known to associate with the progression of chronic hepatitis and the increase risk of hepatocellular carcinoma (HCC). We have reported that iron depletion inhibited the cancer cell proliferation and reciprocally induced angiogenesis. Anti-angiogenic drug synergistically enhanced the anti-tumor effect in iron depletion condition. Sorafenib is molecular-targeting drug with anti-angiogenic effect in HCC. We hypothesized that iron depletion also enhanced the effect of sorafenib and investigated it. [Experimental Design] HepG2 and HLE (Human HCC cell line) were used in this study. We used sorafenib (NexavarTM) and an oral iron chilator, deferasirox (EXJADETM). The anti-cancer effect and mechanism were determined using cell viability assay, VEGF ELISA, Flow Cytometry, Western blot analysis and in vivo subcutaneous tumor model. In clinical cases, we retrospectively analyzed the relationship between sorafenib response and serum iron-related makers(n=58). [Results] In HepG2 and HLE cells, deferasirox suppressed the cancer cell proliferation by itself and increased the suppression of sorafenib. Deferasirox increased VEGF secretion of supernatant on dose dependent manner. In the analysis of combination therapy, cell cycle arrest and apoptosis was enhanced in the combination therapy by down-regulation of cyclinD1 and cyclinE and up-regulation of cleaved PARP. The suppression of HepG2 subcutaneous tumor was enhanced in the combination therapy. In clinical cases, sorafenib prolonged overall survival in TIBC high and Ferritin low group. [Conclusion] Iron depletion by deferasirox increased the anti-cancer effect of sorafenib in vitro and in vivo experiments. In clinical cases, sorafenib was also effective in iron deficient patients. These results suggested that iron depletion therapy can be a novel combination chemotherapy with sorafenib for hepatocarcinoma patients. Citation Format: Shinichi Urano, Toshiaki Ohara, Ryoichi Katsube, Shinichiro Watanabe, Kazuhiro Noma, Yasuko Tomono, Hiroshi Tazawa, Kazuhiro Nouso, Yasuhiro Shirakawa, Toshiyoshi Fujiwara. Iron chelation therapy increased the anticancer effect of sorafenib in hepatocarcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1681. doi:10.1158/1538-7445.AM2014-1681
NK Cells From CLL Patients Exhibit Down-Regulation Of Interferon Response Genes That Can Be Reversed With Lenalidomide
Authors: John C. Riches, Ajanthah Sangaralingam, Tracy Chaplin, Fabienne McClanahan, Sameena Iqbal, Samir G. Agrawal, Alan G. Ramsay, John Gribben
Journal: Blood (2013)
Global patterns and trends in colorectal cancer incidence and mortality
Authors: Melina Arnold, Mónica S Sierra, Mathieu Laversanne, Isabelle Soerjomataram, Ahmedin Jemal, Freddie Bray
Journal: Gut (2016)

<h3>Objective</h3> The global burden of colorectal cancer (CRC) is expected to increase by 60% to more than 2.2 million new cases and 1.1 million deaths by 2030. In this study, we aim to describe the recent CRC incidence and mortality patterns and trends linking the findings to the prospects of reducing the burden through cancer prevention and care. <h3>Design</h3> Estimates of sex-specific CRC incidence and mortality rates in 2012 were extracted from the GLOBOCAN database. Temporal patterns were assessed for 37 countries using data from <i>Cancer Incidence in Five Continents</i> (CI5) volumes I–X and the WHO mortality database. Trends were assessed via the annual percentage change using joinpoint regression and discussed in relation to human development levels. <h3>Results</h3> CRC incidence and mortality rates vary up to 10-fold worldwide, with distinct gradients across human development levels, pointing towards widening disparities and an increasing burden in countries in transition. Generally, CRC incidence and mortality rates are still rising rapidly in many low-income and middle-income countries; stabilising or decreasing trends tend to be seen in highly developed countries where rates remain among the highest in the world. <h3>Conclusions</h3> Patterns and trends in CRC incidence and mortality correlate with present human development levels and their incremental changes might reflect the adoption of more western lifestyles. Targeted resource-dependent interventions, including primary prevention in low-income, supplemented with early detection in high-income settings, are needed to reduce the number of patients with CRC in future decades.
Effect of Obesity on Endothelial Function and Subclinical Atherosclerosis in Children
Authors: Şeref Alpsoy, Aydın Akyüz, Dursun Cayan Akkoyun, Burçin Nalbantoğlu, Birol Topçu, Mustafa Metin Donma, Hasan Değirmenci, Kubilay Erselcan
Journal: Journal of the American College of Cardiology (2013)
Specific Anti_A/B Immunoaffinity Chromatography Step Reduces Isoagglutinin Levels in an Intravenous Immunoglobulin Product
Authors: Alphonse P. Hubsch, Annette Gaida, Ibrahim El Menyawi, Sandra Wymann, A. Adriano Marques, Nicole Spiegl, Thomas Roten, Eleonora Widmer
Journal: Journal of Allergy and Clinical Immunology (2016)
A Phase I Trial Of Anti-KIR Monoclonal Antibody IPH2101 and Lenalidomide For Multiple Myeloma
Authors: Don M. Benson, Adam D Cohen, Craig C Hofmeister, Munshi C Nikhil, Sundar Jagannath, Yvonne A Efebera, Gary Spitzer, Robert Zerbib, Pascale Andre, Shawna Oxier, Michael A. Caligiuri
Journal: Blood (2013)
Pulmonary Carcinogenesis in Rats Given Implants of Cigarette Smoke Condensate in Beeswax Pellets<xref ref-type="fn" rid="FN2">2</xref>
Authors: G. E. Dagle, K. E. McDonald, L. G. Smith, D. L. Stevens, Jr.
Journal: JNCI Journal of the National Cancer Institute (1978)

Lungs of inbred OM/NCR and outbred Sprague-Dawley rats were given implants, through a thoracotomy, of pellets of cigarette smoke condensate (CSC) suspended in a beeswax-tricaprylin vehicle. The pellets slowly released material into the surrounding parenchyma, which resulted in a dose-related increased incidence of lung cancer, predominantly invasive and metastasizing epidermoid carcinoma. A 42% prevalence of pulmonary carcinoma was present in the highest dosage group, which received 67 mg CSC, exposing approximately 1.65 cm2 bronchiolar epithelium. Squamous metaplasia associated with the implanted site preceded the appearance of the carcinomas and was more severe, with the larger pellets having more concentrated CSC. No difference was observed in incidence of pulmonary carcinomas with the use of CSC containing high or low concentrations of nicotine. The potential value of this bioassay system were discussed.
Image Gallery: Linear unilateral basaloid follicular hamartoma: a unique presentation
Authors: S. ElBehairy, A. Elbendary, Z. Moussa
Journal: British Journal of Dermatology (2016)

Funding sources: none. Conflicts of interest: none declared. Dear Editor, A 26‐year‐old woman presented with an asymptomatic linear atrophic lesion on the lower part of the right cheek. The lesion was of nine years’ duration and had a very slowly progressive course. The lesion appears as multiple grouped skin‐coloured pits taking a linear distribution, measuring about 6 cm in length and following Blaschko's lines. Few open comedones were seen within these pits. A skin biopsy was performed. Histopathological examination revealed cords and strands of basaloid cells arising from the hair follicle infundibulum, extending into the upper dermis and surrounded by scant fibrocellular stroma with no retraction. No cellular atypia or atypical mitoses were noted.
Gene expression classifier for prognosis of early-stage squamous cell carcinoma of the lung
Authors: Rintaro Noro, Naomi Walsh, Teruhide Ishigame, Kouya Shiraishi, Ana I. Robles, Bríd M. Ryan, Elise Bowman, Judith A. Welsh, Aaron J. Schetter, Vidar Skaug, Steen Mollerup, Aage Haugen, Jun Yokota, Takashi Kohno, Curtis C. Harris
Journal: Journal of Thoracic Oncology (2016)
Altered type II interferon precedes autoantibody accrual and elevated type I interferon activity prior to systemic lupus erythematosus classification
Authors: Melissa E Munroe, Rufei Lu, Yan D Zhao, Dustin A Fife, Julie M Robertson, Joel M Guthridge, Timothy B Niewold, George C Tsokos, Michael P Keith, John B Harley, Judith A James
Journal: Annals of the Rheumatic Diseases (2016)

The relationship of immune dysregulation and autoantibody production that may contribute to systemic lupus erythematosus (SLE) pathogenesis is unknown. This study evaluates the individual and combined contributions of autoantibodies, type I interferon (IFN-α) activity, and IFN-associated soluble mediators to disease development leading to SLE.Serial serum specimens from 55 individuals collected prior to SLE classification (average timespan=4.3 years) and unaffected healthy controls matched by age (±5 years), gender, race and time of sample procurement were obtained from the Department of Defense Serum Repository. Levels of serum IFN-α activity, IFN-associated mediators and autoantibodies were evaluated and temporal relationships assessed by growth curve modelling, path analysis, analysis of covariance and random forest models.In cases, but not matched controls, autoantibody specificities and IFN-associated mediators accumulated over a period of years, plateauing near the time of disease classification (p<0.001). Autoantibody positivity coincided with or followed type II IFN dysregulation, preceding IFN-α activity in growth curve models, with elevated IFN-α activity and B-lymphocyte stimulator levels occurring shortly before SLE classification (p≤0.005). Cases were distinguished by multivariate random forest models incorporating IFN-γ, macrophage chemoattractant protein (MCP)-3, anti-chromatin and anti-spliceosome antibodies (accuracy 93% >4 years pre-classification; 97% within 2 years of SLE classification).Years before SLE classification, enhancement of the type II IFN pathway allows for accumulation of autoantibodies and subsequent elevations in IFN-α activity immediately preceding SLE classification. Perturbations in select immunological processes may help identify at-risk individuals for further clinical evaluation or participation in prospective intervention trials.
Impact Of The Number Of Prior Treatment Lines Received On The Distribution Of Peripheral Blood Leukocyte Subsets In Advanced-Stage B-Cell Chronic Lymphocytic Leukemia (CLL)
Authors: Georgiana Grigore, Susana Barrena, Martin Perez-Andres, Miriam Fierro, Marcos González, Pilar Rabasa, Angeles Medina, José Francisco Tomás, Fernando Solano, Javier De la Serna, Jose García Marco, Mª José Allegue, Javier Loscertales, Inmaculada PÉrez, Teresa Olave, Julia Almeida, Alberto Orfao
Journal: Blood (2013)
Application of extensively targeted next-generation sequencing for the diagnosis of primary immunodeficiencies
Authors: Daiei Kojima, Xinan Wang, Hideki Muramatsu, Yusuke Okuno, Nobuhiro Nishio, Asahito Hama, Ikuya Tsuge, Yoshiyuki Takahashi, Seiji Kojima
Journal: Journal of Allergy and Clinical Immunology (2016)
Bed crises are occurring almost daily in some hospitals
Authors: J Wardrope, N L Kidner, J Edhouse
Journal: BMJ (1995)

stay and bed use factor are better than the average for Wales, where most hospitals have parallel systems for admitting acute medical and geriatric emergencies.The appointment of a bed manager, flexible use of all acute beds in the hospital, and protocols for early discharge and transfer have failed to prevent constant overflows into non-medical wards, waits on trolleys in the accident and emergency department, and temporary closures, even though some general practices have access to community type hospital beds.Brief analysis (to be audited in more detail) suggests that few of the admissions are inappropriate.Major factors include patients' increased demands and expectations and general practitioners' fear of complaints and litigation.Given this, it is difficult to envisage any reduction in beds, let alone the 30% predicted in acute district general hospitals,3 whose surgeons are already practising day case surgery to a maximum.General practitioners have neither the time nor, probably, the skill needed to treat most of our acute medical admissions, even if they were provided with more facilities.Planning must be modified to take account of these issues.
Prevalence of Familial Hypercholesterolemia in the 1999 to 2012 United States National Health and Nutrition Examination Surveys (NHANES)
Authors: Sarah D. de Ferranti, Angie Mae Rodday, Michael M. Mendelson, John B. Wong, Laurel K. Leslie, R. Christopher Sheldrick
Journal: Circulation (2016)

Background— The prevalence of familial hypercholesterolemia (FH) is commonly reported as 1 in 500. European reports suggest a higher prevalence; the US FH prevalence is unknown. Methods and Results— The 1999 to 2012 National Health and Nutrition Examination Survey (NHANES) participants ≥20 years of age (n=36 949) were analyzed to estimate the prevalence of FH with available Dutch Lipid Clinic criteria, including low-density lipoprotein cholesterol and personal and family history of premature atherosclerotic cardiovascular disease. Prevalence and confidence intervals of probable/definite FH were calculated for the overall population and by age, sex, obesity status (body mass index ≥30 kg/m 2 ), and race/ethnicity. Results were extrapolated to the 210 million US adults ≥20 years of age. The estimated overall US prevalence of probable/definite FH was 0.40% (95% confidence interval, 0.32–0.48) or 1 in 250 (95% confidence interval, 1 in 311 to 209), suggesting that 834 500 US adults have FH. Prevalence varied by age, being least common in 20 to 29 year olds (0.06%, 1 in 1557) and most common in 60 to 69 year olds (0.85%, 1 in 118). FH prevalence was similar in men and women (0.40%, 1 in 250) but varied by race/ethnicity (whites: 0.40%, 1 in 249; blacks: 0.47%, 1 in 211; Mexican Americans: 0.24%, 1 in 414; other races: 0.29%, 1 in 343). More obese participants qualified as probable/definite FH (0.58%, 1 in 172) than nonobese (0.31%, 1 in 325). Conclusions— FH, defined with Dutch Lipid Clinic criteria available in NHANES, affects 1 in 250 US adults. Variations in prevalence by age and obesity status suggest that clinical criteria may not be sufficient to estimate FH prevalence.
Abstract 9140: The Majority of Plakophilin-2 Mutations in Arrhythmogenic Cardiomyopathy are Associated with Haploinsufficiency in the Myocardium and Epidermis
Authors: Torsten B Rasmussen, Peter H Nissen, Johan Palmfeldt, Katja Gehmlich, Søren Dalager, Uffe B Jensen, Won Y Kim, Lene Heickendorff, Henning Mølgaard, Henrik K Jensen, Ulrik T Baandrup, Peter Bross, Jens Mogensen
Journal: Circulation (2012)

Background: Arrhythmogenic cardiomyopathy (AC) is a hereditary cardiac condition associated with ventricular arrhythmias, heart failure and sudden death. The disease is most often caused by mutations in the desmosomal gene for plakophilin-2 (PKP2), which is expressed in both myocardial and epidermal tissue. It was the aim of this study to investigate protein expression in myocardial tissue of ARVC patients carrying PKP2 mutations and elucidate if keratinocytes of the same individuals exhibited a similar pattern of protein expression. Methods and Results: Direct sequencing of 5 ARVC-genes in 71 unrelated ARVC patients identified 10 different PKP2 mutations. One patient, a digenic carrier of heterozygous PKP2- and desmoglein-2 mutations, developed severe heart failure and underwent cardiac transplantation. Western blotting and immunohistochemistry of the explanted heart showed a significant decrease in PKP2 protein expression without detectable amounts of truncated PKP2 protein. Cultured keratinocytes of the patient showed a similar reduction in PKP2 protein expression. Nine additional PKP2 mutations were investigated in both cultured keratinocytes and endomyocardial biopsies from affected individuals. It was evident that PKP2 mutations introducing a premature termination codon in the reading frame were associated with reduced PKP2 transcript and protein levels while a missense variant did not affect PKP2 expression levels. Conclusion: This study indicated that the majority of PKP2 mutations in ARVC are associated with haploinsufficiency. Furthermore, myocardial PKP2 expression in mutation carriers correlate well with PKP2 expression in keratinocytes of the same individuals. This finding makes keratinocyte cultures a promising new tool to characterize desmosomal protein expression in AC patients. Figure legend: A) The explanted heart of a digenic mutation carrier with AC, B) Western blotting of PKP2, C) Western blotting of DSG2
Changes in the inflammatory microenvironment in premalignant colonic adenomatous polyps: Evidence for immunosurveillance?
Authors: David Mansouri, James Hugh Park, Clare Orange, Emilia M. Crighton, Paul G. Horgan, Donald C. Mcmillan
Journal: Journal of Clinical Oncology (2015)

535 Background: The majority of colorectal cancers develop through the adenoma-carcinoma sequence. Recently, the host inflammatory response has become recognized as a key determinant of outcome. In particular, a pronounced peri-tumoral local inflammatory infiltrate identifies those with a better outcome. The present study aimed to characterize the local inflammatory response in pre-malignant colorectal adenomatous polyps. Methods: Patients with adenomatous polyps removed at colonoscopy as part of a population FOBt screening program were identified from a prospectively maintained database. All polyps were greater than 1cm. Whole slide immunohistochemistry was performed to assess intraepithelial T-cell (CD3 + ), cytotoxic T-cell (CD8 + ) and macrophage (CD68 + ) infiltrate. Inter-observer agreement for assessment of inflammatory cell infiltrate was good or better for CD3 + , CD8 + and CD68 + staining (Kappa 0.66, 0.66, 0.79 respectively). Results: A total of 207 adenomatous polyps, 107 high-grade (HG), 100 low-grade (LG), from 134 patients were included. Median age was 65 years, 33 (25%) were female and 15 (11%) were taking regular aspirin. Comparing HG and LG polyps, there were more older and female patients in the HG group (p&lt;0.05). There was no difference in location (p=0.222), macroscopic morphology (p=0.445) or aspirin (p=0.377) use between groups. Microscopically, HG polyps were more likely to contain a villous component than LG polyps (65% vs 50%, p&lt;0.05). Overall, high levels of CD3 + , CD8 + and CD68 + infiltrate were observed in 68%, 25% and 72% of polyps respectively. Both CD3 + (74% vs 61%, p&lt;0.05) and CD8 + (37% vs 13%, p&lt;0.001) infiltrate was higher in HG polyps compared to LG polyps. There was no association with polyp grade and CD68 + infiltrate (74% vs 70%, p=0.540). Conclusions: An increase in local T-lymphocytic infiltrate, but not macrophage infiltrate was identified with progression from low-grade to high-grade dysplasia. This would suggest a specific response to early disease progression confirming increased immunosurveillance. Therefore, such early stage disease may amenable to immunomodulatory treatment.
New Attempt to Curb Opioid Abuse
Authors: Rebecca Voelker
Journal: JAMA (2016)

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Heterogeneity in the breakpoints in balanced rearrangements involving band 12p13 in hematologic malignancies identified by fluorescence in situ hybridization: TEL (ETV6 ) is involved in only one half.
Authors: Yuko Sato, Stefan K. Bohlander, Hirofumi Kobayashi, Shalini Reshmi, Yoshimasa Suto, Elizabeth M. Davis, Rafael Espinosa, Richard Hoopes, Kate T. Montgomery, Raju S. Kucherlapati, Michelle M. Le Beau, Janet D. Rowley
Journal: Blood (1997)
Risk factors for early mortality, relapse and overall survival in new cases of APL treated by arsenic trioxide
Authors: K. Alimoghaddam, A. Ghavamzadeh, S. Rostami, S. Ghaffari, R. Hosseini, B. Bahar, E. Baybordi, P. Radsafa, M. Shadpoor, E. Eini, S. Abdolahi
Journal: Journal of Clinical Oncology (2007)

7069 Background: There are several known risk factors for APL treatment by ATRA and chemotherapy, but risk factors for new cases of APL treated by Arsenic Trioxide are unknown. Methods: Between May 2000 and September 2006, we treated 141 new cases of APL (Median age 28±12.8 y/o min=11, max=71) by 2 hours iv infusion of 0.15mg/kg ATO until complete remission. Trial approved by IRB and consent form obtained. Diagnosis was by clinical and morphologic characteristics and confirmed by cytogenetic and RT-PCR for detection of t(15,17) and presence of PML-RARa. After complete remission patients received consolidation by 28 days infusion of ATO for one or four courses. Known risk factors for APL treatment outcome (including PML-RARa isoforms, presence of MRD during follow up and WBC count at presentation analyzed for early mortality, relapse rate, DFS and OS. Results: Complete remission observed in 121 cases (85.8%) and early mortality rate was 14.9%. short isoform of detected in 36% of patients and 18% presented by WBC more than 10,000/μl. For early mortality, APL differentiation syndrome during treatment and WBC count more than 10,000/μl were risk factors. (P&lt;0.001 and p=0.011 respectively) For DFS only predicting factor for relapse was detection of MRD (by nested PCR or by real time PCR) during follow up (P=0.05). For prediction of OS, again only risk factor was detection of MRD(P&lt;0.0001). Conclusions: Although WBC count before treatment and APL differentiation syndrome during treatment are risk factor for relapse, short isoform of APL is not a risk factor. After achieving to CR only risk factor is detection of MRD. No significant financial relationships to disclose.