tbuckley/cabot-search huggingface dataset:
A prospective randomized comparison of continuous infusion fluorouracil with a conventional bolus schedule in metastatic colorectal carcinoma: a Mid-Atlantic Oncology Program Study.
Authors: J J Lokich, J D Ahlgren, J J Gullo, J A Philips, J G Fryer
Journal: Journal of Clinical Oncology (1989)

One hundred seventy-nine patients with advanced measurable colorectal cancer not previously treated with chemotherapy were entered into a prospective randomized clinical trial by the Mid-Atlantic Oncology Program (MAOP) to compare two schedules of delivery for single-agent fluorouracil (5-FU). The "standard" treatment was a schedule commonly employed in clinical practice, namely, a daily bolus dose administered intravenously (IV) for five consecutive days and repeated at 5-week intervals. The investigational treatment was a continuous infusion of 5-FU administered 24 hours a day for a protracted time (10 weeks or more). Both treatments were continued until the development of disease progression or unless interrupted for toxicity. Using stringent objective criteria requiring independent confirmation of x-ray or scan-documented response, the tumor response rate reached 7% (six of 87) for the bolus arm and 30% (26 of 87) for the infusion arms (P less than .001). Toxicity was substantially different for the two arms with major leukopenia observed only on the bolus arm, 22% developing grade 3 (severe) or grade 4 (life-threatening) leukopenia with four sepsis-related deaths. Hand-foot syndrome was observed only in the infusional arm, requiring treatment interruptions and dose reductions in 24% of patients, but with little impact on quality of life. In spite of the major difference in objective response rate, overall survival for the two groups was comparable. Administration of 5-FU as a continuous infusion for protracted periods clearly improves the therapeutic index for this agent in patients with advanced colon cancer with respect to response rate and reduced toxicity. This schedule appears workable in the community setting and yields response rates similar to those reported for 5-FU with high-dose leucovorin, but without the gastroin testinal toxicity profile of the latter combination.
BH3 profiling can determine dependence on antiapoptotic Bcl-2 family members and can predict response to chemotherapeutic agents.
Authors: Joslyn Brunelle, Jing Deng, Anthony Letai
Journal: Clinical Cancer Research (2008)

A18  Bcl-2 family member proteins regulate the mitochondrial pathway of apoptosis. These family members can be divided into anti-apoptotic proteins and pro-apoptotic proteins. Pro-apoptotic proteins can be further divided into multi-domain (Bax and Bak) and BH3 only (including Bid, Bim, Bad, Noxa,etc.). All Bcl-2 family proteins have at least one BH domain which share sequence homology and are involved in protein interactions. Anti-apoptotic Bcl-2 family proteins (Bcl-2, Bcl-XL, Mcl-1) function by binding and sequestering pro-apoptotic proteins. Anti-apoptotic proteins show preferential binding to certain pro-apoptotic BH3-only proteins, as determined by fluorescent polarization. For example, Bcl-2 can bind to Bad, whereas Mcl-1 can bind to Noxa.  BH3 profiling is a technique that utilizes this distinct binding code in order to determine whether cells are dependent on anti-apoptotic proteins for survival. Peptides that match the BH3 domain sequence of Bcl-2 family proteins are used. When added to isolated mitochondria these BH3 peptides can induce release of cytochrome c, which provides a functional read out for the measurement of dependence on anti-apoptotic proteins. BH3 profiling can distinguish between Bcl-2 and Mcl-1 dependence in primary leukemia from genetically designed mouse models and cell lines, as well as leukemia samples from human patients. In addition, we show that Bcl-2 and Mcl-1 are primed with the pro-apoptotic BH3-only proteins Bim and Puma and not Bax or Bak. BH3 profiling can also identify three classes of apoptotic blocks, which are (A) loss of pro-apoptotic BH3 only protein, (B) loss of pro-apoptotic Bax and Bak, and (C) overexpression of anti-apoptotic proteins (Bcl-2, Bcl-XL, Mcl-1). Class A and B blocks would be resistant to chemotherapeutic agents, while a Class C block would be sensitive to chemotherapeutic agents. Cells that are Bcl-2 dependent according to BH3 profiling would be sensitive to the Bcl-2 antagonist ABT-737.
Enzyme Activities in Induced and Serially Transplanted Murine Mammary Adenocarcinomas2
Authors: S. Abraham, J. Bartley, K. B. DeOme, L. J. Faulkin, Daniel Medina
Journal: JNCI Journal of the National Cancer Institute (1973)

Journal Article Enzyme Activities in Induced and Serially Transplanted Murine Mammary Adenocarcinomas Get access S. Abraham, S. Abraham 3Bruce Lyon Memorial Research Laboratory, Children's Hospital Medical Center, Oakland, Calif. 94609 Search for other works by this author on: Oxford Academic PubMed Google Scholar J. Bartley, J. Bartley 3Bruce Lyon Memorial Research Laboratory, Children's Hospital Medical Center, Oakland, Calif. 94609 Search for other works by this author on: Oxford Academic PubMed Google Scholar K. B. DeOme, K. B. DeOme 4Department of Zoology and Its Cancer Research Laboratory, University of California, Berkeley, Calif. 94720 Search for other works by this author on: Oxford Academic PubMed Google Scholar L. J. Faulkin, L. J. Faulkin 5Department of Anatomy, School of Veterinary Medicine, University of California, Davis, Calif. 95616 Search for other works by this author on: Oxford Academic PubMed Google Scholar Daniel Medina, Jr. Daniel Medina, Jr. 6Department of Anatomy, Baylor College of Medicine, Texas Medical Center, Houston, Tex. 77025 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 51, Issue 1, July 1973, Pages 251–256, https://doi.org/10.1093/jnci/51.1.251 Published: 01 July 1973 Article history Received: 11 January 1973 Accepted: 27 February 1973 Published: 01 July 1973
Phase II clinical study of erlotinib for treatment of myelodysplastic syndromes
Authors: Rami S. Komrokji, Eric Padron, Daohai Yu, William J. Fulp, Yuraima Rodriguez, Sara Tinsley, Alan F. List, Jeffrey E. Lancet
Journal: American Journal of Hematology (2014)

Outcome in patients with myelodysplastic syndrome (MDS) after azanucleoside failure is poor with unmet need for active novel agents. Preclinical data have suggested that erlotinib has in vivo and in vitro off epidermal growth factor receptor (EGFR)-target activity in MDS. We conducted a phase II study with single-agent erlotinib 150 mg/day orally in MDS patients following azanucleoside failure. All intermediate-2 or high-risk MDS patients by International Prognostic Scoring System and only those low/intermediate-1 patients with transfusion-dependent anemia or platelet counts <50 × 10(9) /L or a significant clinical hemorrhage requiring platelet transfusion or ANC <1 × 10(9) /L were eligible, with most of our patients being at high risk. In 35 eligible patients, overall best response was 14% (3 patients having marrow complete response and 2 hematological improvement). Four deaths occurred on study (sepsis, intracranial hemorrhage, sudden death, and acute myeloid leukemia (AML)). The most common observed grade 3/4 toxicities according to CTCAE v3 were diarrhea (17.1%), rash (17.1%), and infection (11.6%), accompanied by fatigue, thrombocytopenia, and anorexia at 5.7% each. Median overall survival was 6.8 months (95% CI 4.9-13.2), and leukemia-free survival was 5 months (95% CI 3.4-7.3). Erlotinib was generally well tolerated, with modest single-agent activity. Given these results and preclinical data suggesting synergistic effect with azanucleosides, the combination should be further explored.
Tracheobronchopathia osteochondroplastica - Analysis of 10 years period
Authors: Milda Nanushi, Jolanda Nikolla, Hasan Hafizi
Journal: European Respiratory Journal (2012)

Background : Tracheobronchopathia osteochondroplastica (TO) is a pulmonary orphan disease and consists at the presence of multiple osseous or cartilaginous nodules localised in the submucosa of the tracheobronchial wall. These nodules protrude into the lumen of the trachea and the large bronchi, leading to the airway obstruction.The disease does not involve other organs.   Method : We studied in retrospective all cases of TO diagnosed with fiberoptic bronchoscopy for the period 2001 - 2011. In our hospital we realise aproximately 1200 bronchocopies per year.   Results : We found 17 cases, 52 % were female and 48 % male. The average age was 40.6 years, 42 % were smokers (∼40 UPA) without family history for TO. The duration of symptoms till the diagnostic was 2.3 years. The most frequent symptoms were: cough 100 %, sputum 64 %, dyspnea 41 %, haemoptisis 5 %, and erythema nodosa 5 %. The laboratory findings demonstrate an increase of sediment in 58 % of cases, 11 % leucocytosis and all the others were normal. Proteus mirabilis was the most frequent microbiological strain (17 %). Functional respiratory tests resulted: 35 % obstruction, 11 % restriction, 5 % mixed and 17 % normal. The bronchial biopsy demonstrated epithelial displasia and fibrosis stroma with inflammatory elements. One case was accompanied with bronchial cancer. The treatment was with antibiotics and symptomatic.  We didn9t have the possibility to realize FBS reevaluation for judging the disease9s evolution.   Conclusions:  TO present frequently with chronic or acute non specific respiratory symptoms, but with pathognomonic characteristic features in FBS. Thoracic CT scanner is a non invasive diagnostic method. The treatment is symptomatic.
Anti-depressants in severe and brittle asthma patients on long term corticosteroids: An observational study
Authors: Rahul Bhat, Adel H. Mansur, Verity Mitchell
Journal: European Respiratory Journal (2013)

Introduction: Anxiety and depression is highly prevalent in patients with difficult-to-control asthma. Previous studies have also shown significantly higher depressive symptoms in patients on long term corticosteroids.  Objective: The purpose of the study was to measure the effect of antidepressants in brittle asthma patients on long term steroids compared to those not on long term corticosteroids.  Methods: We studied patients on the severe and brittle asthma register on long term corticosteroids (n=57) and patients not on long term corticosteroids(n=83). We then made two subgroups of each group one on antidepressants and one not on anti depressants. The HADS-D(Hospital Anxiety Depression scale-Depression) scores of 2 subgroups on anti-depressants(on steroids n=7 and not on steroids n=9) were compared.Both groups had mean age of 40.8 and no significant difference in the mean pre-bronchodialator FEV1 and similar Asthma Control Questionnaire(ACQ) scores.  Results:1)Mean HADS-D score of steroid dependant group and non-steroid dependant group were 11.3 and 4.2 respectively(p  2)Mean HADS-D scores were 11.58 and 10.28 in the no antidepressant and antidepressant sub-groups respectively(p=0.93) in the steroid dependant group. Mean ACQ scores were 3.8 and 3.58 respectively (p=0.36). Conclusions: 1)Study confirms level of depressive symptoms are significantly higher in the steroid dependant group in Brittle Asthma.  2) Anti- depressants are less effective in the steroid dependant group after correcting for Age, pre-bronchodialator FEV1 and ACQ scores as measured by the HADS-D scale.
The roles of Ki-67, p53, transforming growth factor- and lysyl oxidase in the metastasis of lung cancer
Authors: Omer Araz, Elif Demirci, Elif Yilmazel Ucar, Muhammet Calik, Adem Karaman, Irmak Durur Subasi, Ebru Orsal, Mahmut Subasi, Ferah Daloglu, Metin Akgun
Journal: European Respiratory Journal (2014)

Objectives : This study aimed to evaluate the microscopic predictive molecular markers that play roles in metastasis. The secondary aim of the study was the investigation of the relationship between these parameters and the SUVmax of the primary lesion, obtained by PET-CT.  Methods : Eighty-five patients with newly diagnosed LC were enrolled in this study. All patients were examined using the PET-CT and brain magnetic resonance imaging. Ki-67, p53, transforming growth factor-β (TGF-β), and lysyl oxidase (LOX) were evaluated histopathologically in all of the cases.  Results : Immunohistochemical evaluations revealed small cell lung carcinoma (SCLC) as showing the most intense staining in all parameters and differentiated adenocarcinoma demonstrated a more diffuse and intense staining than squamous cell carcinoma (SCC). There was a statistically significant relationship between the parameters of TGF-β, LOX, and the metastasis of adenocarcinoma in terms of diffusivity and intensity; however, p53 and Ki-67 did not show a statistically significant relationship. These four parameters obtained from both the SCLC and SCC cases demonstrated no correlation to the SUVmax. In the case of adenocarcinoma, the diffusivity and intensity of the LOX and p53 staining showed a statistically significant relationship to the SUVmax; but for the other parameters, a statistically significant relationship was not seen.  Conclusion : LOX and TGF-β may play roles in cases of metastases in lung adenocarcinoma. The inhibition of these factors and their signaling pathways can be used as a method of treatment for lung cancer.
Association between adult atopic dermatitis, cardiovascular disease, and increased heart attacks in three population‐based studies
Authors: J. I. Silverberg
Journal: Allergy (2015)

Abstract Background Adults with eczema are more likely to smoke cigarettes, consume alcohol, and have sedentary lifestyle. We sought to determine whether adult eczema is associated with increased cardiovascular and cerebrovascular disease. Methods Data from the 2005–2006 National Health and Nutrition Examination Survey ( NHANES ) ( n = 4970) and 2010 ( n = 27 157) and 2012 ( n = 34 525) National Health Interview Survey ( NHIS ). History of coronary artery disease ( CAD ), angina, heart attack, stroke, and peripheral vascular disease ( PVD ) were determined. Results In NHANES , flexural eczema in the past year was associated with significantly higher odds of CAD ( P ≤ 0.04), heart attack ( P ≤ 0.01), and congestive heart failure ( P ≤ 0.02), but not with stroke ( P ≥ 0.37), in survey‐weighted multivariate logistic regression models that controlled for socio‐demographics, comorbid asthma, and hay fever. Similarly, in NHIS 2010 and 2012, 1‐year history of eczema was associated with significantly higher odds of CAD ( P ≤ 0.02), angina ( P ≤ 0.02), heart attack ( P ≤ 0.047), other heart disease ( P &lt; 0.0001), stroke ( P ≤ 0.02), and PVD (&lt;0.0001) in multivariate models. Conclusions Adults with atopic dermatitis may have increased cardiovascular disease, heart attack, and stroke.
Identification of atopy amongst wheezing infants via electronic nose
Authors: Marc P. van der Schee, Simone Hashimoto, Marlous van den Ouweland, Nora Adriaens, Anne-Marie C. Schuurman, Aline B. Sprikkelman, Eric G. Haarman, Wim M.C. van Aalderen, Peter J. Sterk
Journal: European Respiratory Journal (2014)

Rationale: Infants with physician confirmed wheeze have higher risk of developing asthma. Moreover, there is increased evidence on the role of atopy as contributor to a high risk phenotype for severe airway diseases. Non-invasive biomarkers have been used in the assessment of various clinical and inflammatory characteristics.We aimed to determine whether electronic nose (eNose) can identify atopic sensitization to common allergens amongst wheezy infants.

Methods: Cross-sectional analysis from the EUROPA study (n=1212), an unbiased birth cohort aimed at early diagnose of asthma in infants. Wheeze was confirmed by a trained physician during a period of acute respiratory symptoms. Blood and exhaled breath were collected in wheezy infants and healthy controls (no history of wheeze or dyspnea). Specific IgE was investigated by ImmunoCAP Immuno Solid-phase Allergen Chip (Phadia, Sweden) and exhaled breath was analyzed by eNose. Raw eNose data was analyzed using principal component and discriminant analysis and ROC-curves were constructed.

Results: 64 wheezy infants (42 male, 29.2±3.2months) and 73 healthy controls (38 male, 26.9±2.4 months) were included. Sensitization to any allergen (cut-off 0.3 ISU) was present in 49 (79%) and 51 (69%) infants, respectively. Breath prints differed significantly between wheezy infants sensitized and not sensitized (AUC of ROC = 0.74±0.07, p value=0.008). There were no differences in the exhaled breath profiles between healthy controls sensitized and not sensitized (p value=0.14).

Conclusion: eNose can discriminate atopic and non-atopic wheezy infants with moderate accuracy. These findings support the added value of non-invasive biomarkers in the phenotyping of wheezy infants.
The relationship between dementia and elder abuse
Authors: A C Coyne, W E Reichman, L J Berbig
Journal: American Journal of Psychiatry (1993)

Alzheimer's disease and other dementias may be associated with greater risk for physical abuse than other illnesses of the elderly. The authors examined the relationship between dementia and abusive behavior in a group of demented patients and their caregivers.An anonymous questionnaire was distributed to 1,000 caregivers who called a telephone help line specializing in dementia. Demographic characteristics of patients and caregivers were assessed, the occurrence of abuse was examined, and caregivers completed the Zarit Burden Interview and the Zung Self-Rating Depression Scale.Questionnaires were completed by 342 caregivers. The mean age of caregivers was 56.1 years; 163 (54.5%) were adult children caring for parents, 111 (37.1%) cared for spouses, and 25 (8.4%) cared for other relatives. Thirty-three caregivers (11.9%) reported that they had directed physically abusive behavior (e.g., pinching, shoving, biting, kicking, striking) toward the dementia patient in their care. These caregivers had been providing care for more years, cared for patients functioning at a lower level, displayed higher burden scores, and displayed higher depression scores than caregivers who reported no abuse. In addition, 92 caregivers (33.1%) reported that the patient directed abuse toward them during the course of providing care. Caregivers who had been abused by patients, in comparison to those who had not, were more likely to direct abusive behavior back toward the patient in their care.These results support the hypothesis that abuse involving cognitively impaired older adults and their caregivers may be associated with the relatively high psychological and physical demands placed on family members who care for relatives with dementia.
Dermoscopy of discoid lupus erythematosus
Authors: A. Lallas, Z. Apalla, I. Lefaki, E. Sotiriou, E. Lazaridou, D. Ioannides, D. Tiodorovic-Zivkovic, T. Sidiropoulos, D. Konstantinou, V. Di Lernia, G. Argenziano, I. Zalaudek
Journal: British Journal of Dermatology (2012)

Summary Background Dermoscopy is useful in evaluating skin tumours, but its applicability also extends into the field of inflammatory skin disorders. Discoid lupus erythematosus (DLE) represents the most common subtype of cutaneous lupus erythematosus. While dermoscopy and videodermoscopy have been shown to aid the differentiation of scalp DLE from other causes of scarring alopecia, limited data exist concerning dermoscopic criteria of DLE in other locations, such as the face, trunk and extremities. Objective To describe the dermoscopic criteria observed in a series of patients with DLE located on areas other than the scalp, and to correlate them to the underlying histopathological alterations. Methods DLE lesions located on the face, trunk and extremities were dermoscopically and histopathologically examined. Selection of the dermoscopic variables included in the evaluation process was based on data in the available literature on DLE of the scalp and on our preliminary observations. Analysis of data was done with SPSS analysis software. Results Fifty-five lesions from 37 patients with DLE were included in the study. Perifollicular whitish halo, follicular keratotic plugs and telangiectasias were the most common dermoscopic criteria. Statistical analysis revealed excellent correlation between dermoscopic and histopathological findings. Notably, a time-related alteration of dermoscopic features was observed. Conclusions The present study provides new insights into the dermoscopic variability of DLE located on the face, trunk and extremities.
Antigenic Properties of Experimental Leukemias. I. Serological Studies &lt;italic&gt;In Vitro&lt;/italic&gt; With Spontaneous and Radiation-Induced Leuke-mias&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Lloyd J. Old, Edward A. Boyse, Elisabeth Stockert
Journal: JNCI Journal of the National Cancer Institute (1963)

Antisera prepared in C57BL/6 mice against several spontaneous or radiation-induced leukemias of strain A, or against a radiation-induced (C57BL/6 × A)F1 leukemia, were cytotoxic in vitro for the cells of 14 radiation-induced C57BL/6 leukemias and 1 C57BL/6 leukemia induced by urethan. These antisera were not cytotoxic for any of the normal C57BL/6 tissues studied. Specific cytotoxic activity was removed by absorption with those C57BL/6 leukemias that are sensitive in the cytotoxic test, but not by normal C57BL/6 tissue. Cytotoxic activity was removed by absorption with normal thymus of strains A, (C57BL/6 × A)F1, and C58, but not with normal thymus of several other strains, including C57-BL/6. Normal strain A tissues, other than thymus, did not absorb specific cytotoxic activity. These serological data indicate the presence of a common antigenic component in certain C57-BL/6 leukemias and in the normal thymus and leukemias of strains A and C58 origin. In conformity with presence of the antigen in the thymus of normal strain A mice, cytotoxic activity against strain A leukemias was not demonstrable in the sera of strain Amice immunized against cross-reacting C57-BL/6 leukemias.
Genetic Modifiers of Age at Onset in Carriers of the G206A Mutation in<i>PSEN1</i>With Familial Alzheimer Disease Among Caribbean Hispanics
Authors: Joseph H. Lee, Rong Cheng, Badri Vardarajan, Rafael Lantigua, Dolly Reyes-Dumeyer, Ward Ortmann, Robert R. Graham, Tushar Bhangale, Timothy W. Behrens, Martin Medrano, Ivonne Z. Jiménez-Velázquez, Richard Mayeux
Journal: JAMA Neurology (2015)

The present study identified potential genetic modifiers that may delay or accelerate age at onset of familial Alzheimer disease (AD) by examining age at onset in PSEN1 mutation carrier families, and further investigation of these modifiers may provide insight into the pathobiology of AD and potential therapeutic measures.To identify genetic variants that modify age at onset of AD.Using a subset of Caribbean Hispanic families that carry the PSEN1 p.G206A mutation, we performed a 2-stage genome study. The mutation carrier families from an ongoing genetic study served as a discovery set, and the cohort of those with LOAD served as a confirmation set. To identify candidate loci, we performed linkage analysis using 5 p.G206A carrier families (n = 56), and we also performed whole-exome association analysis using 31 p.G206A carriers from 26 families. To confirm the genetic modifiers identified from the p.G206A carrier families, we analyzed the GWAS data for 2888 elderly individuals with LOAD. All study participants were Caribbean Hispanics.Age at onset of AD.Linkage analysis of AD identified the strongest linkage support at 4q35 (LOD [logarithm of odds] score, 3.69), and the GWAS of age at onset identified variants on 1p13.1, 2q13, 4q25, and 17p11. In the confirmation stage, genewise analysis identified SNX25, PDLIM3, and 3 SH3 domain genes (SORBS2, SH3RF3, and NPHP1) to be significantly associated with LOAD. Subsequent allelic association analysis confirmed SNX25, PDLIM3, and SORBS2 as genetic modifiers of age at onset of EOAD and LOAD and provided modest support for SH3RF3 and NPHP1.Our 2-stage analysis revealed that SNX25, PDLIM3, and SORBS2 may serve as genetic modifiers of age at onset in both EOAD and LOAD.