tbuckley/cabot-search huggingface dataset:
Molecular Screening for Hereditary Nonpolyposis Colorectal Cancer: A Prospective, Population-Based Study
Authors: Antonio Percesepe, Francesca Borghi, Mirco Menigatti, Lorena Losi, Moira Foroni, Carmela Di Gregorio, Giuseppina Rossi, Monica Pedroni, Elisa Sala, Fabiana Vaccina, Luca Roncucci, Piero Benatti, Alessandra Viel, Maurizio Genuardi, Giancarlo Marra, Paula Kristo, Paivi Peltomäki, Maurizio Ponz de Leon
Journal: Journal of Clinical Oncology (2001)

PURPOSE: Germline mutations in mismatch repair genes predispose to hereditary nonpolyposis colorectal cancer (HNPCC). To address effective screening programs, the true incidence of the disease must be known. Previous clinical investigations reported estimates ranging between 0.5% and 13% of all the colorectal cancer (CRC) cases, whereas biomolecular studies in Finland found an incidence of 2% to 2.7% of mutation carriers for the disease. The aim of the present report is to establish the frequency of the disease in a high-incidence area for colon cancer. PATIENTS AND METHODS: Through the data of the local CRC registry, we prospectively collected all cases of CRC from January 1, 1996, through December 31, 1997 (N = 391). Three hundred thirty-six CRC cases (85.9% of the incident cases) were screened for microsatellite instability (MSI) with six to 12 mono- and dinucleotide markers. MSI cases were subjected to MSH2 and MLH1 germline mutation analysis and immunohistochemistry; the methylation of the promoter region was studied for MLH1. RESULTS: Twenty-eight cases (8.3% of the total) showed MSI. MSI cases differed significantly from microsatellite-stable (MSS) cases for their proximal location (P &lt; .01), high mucinous component (P &lt; .01), and poor differentiation (P = .002). Of MSI cases studied (n = 12), only one with a family history compatible with HNPCC had a germline mutation (in MSH2). Five other patients with a family history of HNPCC (two with MSI and three with MSS tumors) did not show germline mutations. CONCLUSION: We conclude that the incidence of molecularly confirmed HNPCC (one [0.3%] of 336) in a high-incidence area for CRC is lower than in previous biomolecular and clinical estimates.
Endothelial Cells Enhance the Migration of Bovine Meniscus Cells
Authors: Xiaoning Yuan, George M. Eng, Derya E. Arkonac, Pen‐hsiu Grace Chao, Gordana Vunjak‐Novakovic
Journal: Arthritis & Rheumatology (2014)

To study the interactions between vascular endothelial cells and meniscal fibrochondrocytes from the inner avascular and outer vascular regions of the meniscus and to identify angiogenic factors that enhance cell migration and integrative repair. Bovine meniscal fibrochondrocytes (bMFCs) from the inner and outer regions of meniscus were cultured for 7 days with or without human umbilical vein endothelial cells (HUVECs) in a micropatterned 3-dimensional hydrogel system for assessment of cell migration. Angiogenic factors secreted by HUVECs were probed for their role in paracrine mechanisms governing bMFC migration and applied to a full-thickness defect model of meniscal repair in explants from the inner and outer meniscal regions over 4 weeks. Endothelial cells enhanced the migration of inner and outer bMFCs in the micropatterned system via endothelin 1 (ET-1) signaling. Supplementation with ET-1 significantly enhanced the integration strength of full-thickness defects in the inner and outer explants, as well as cell migration at the macroscale level, as compared to controls without ET-1 treatment. This study is the first to show that bMFCs from both the avascular and vascular regions of the meniscus respond to the presence of endothelial cells with increased migration. Paracrine signaling by endothelial cells regulates the bMFCs differentially by region, but we identified ET-1 as an angiogenic factor that stimulates the migration of inner and outer cells at the microscale level and the integrative repair of inner and outer explants at the macroscale level. These findings reveal the regional interactions between the vasculature and MFCs, and suggest ET-1 as a potential new treatment for avascular meniscus injuries in order to prevent the development of osteoarthritis.
Parenchymal cell populations involved in the development of fibrosis
Authors: Birgitta Christine Heckl, Isis Enlil Fernandez Buelvas, Katharina Heinzelmann, Oliver Eickelberg
Journal: European Respiratory Journal (2014)

Lung fibrosis is a severe, chronic lung disease, with a median survival of 3 – 5 years after diagnosis. While there has been significant progress in defining cell-specific functions in disease development and progression, a detailed analysis of definitive cell compartments during fibrosis remains to be elucidated.  Intratracheal installation of bleomycin (3U/Kg) or PBS was performed in C57/bl6 mice, and single cell suspensions of the lungs were obtained at day 14 after treatment. To analyze dynamic changes in the parenchyma, epithelial, endothelial, and mesenchymal markers were used for flow cytometry analysis. Parenchymal CD45- cells were sorted and further analyzed by immunofluorescence staining for epithelial, endothelial cells and mesenchymal cells.  FACS analysis of single cell suspensions from lung homogenates confirmed an increase in cellularity during the onset of fibrosis. Cell-specific analysis for mesenchymal, endothelial, and epithelial markers revealed an increase in CD45- cells at day 14 to 3.3x10 6  (144.75%), compared with 2.3x10 6  (100%) of controls. Epithelial cells were gated as CD45-, EpCAM+ and showed a slight increase during fibrosis (6.1x10 5  -132.46%- vs. 4.6x10 5  -100%-). Endothelial CD45-, CD31+ cells showed up to two-fold increase (2.8x10 6  -187.30%- vs. 1.5x10 6  -100%-), similar to the mesenchymal CD45-, CD90.2+ population (2.7x10 5  -274.59%- vs. 1.0x10 5  -100%-). Sorted CD45- CD31+ CD90.2 -cells showed a positive staining for T1α, E-Cadherin, proSPC and α-SMA.  Our results show that an overall increase in cellularity is a critical determinant of parenchymal expansion in lung fibrosis. To characterize these populations more in detail, further analysis needs to be done.
Intercellular adhesion molecule-1 (ICAM-1) and endothelial leucocyte adhesion molecule-1 (ELAM-1) expression in the bronchial mucosa of normal and asthmatic subjects
Authors: S Montefort, WR Roche, PH Howarth, R Djukanovic, C Gratziou, M Carroll, L Smith, KM Britten, D Haskard, TH Lee, al. et
Journal: European Respiratory Journal (1992)

Bronchial lavage and biopsy studies suggest the involvement of eosinophils and T-lymphocytes in allergic inflammation in asthma. There is evidence suggesting that the expression of adhesion molecules on endothelial cells and of their receptors on leucocytes is involved in this process. To investigate these mechanisms we have obtained bronchial mucosal biopsies from 10 normal subjects and from 10 symptomatic atopic asthmatics. Six of the asthmatics were re-biopsied after 6 weeks of inhaled beclomethasone dipropionate (BDP) during which time their clinical response was monitored. Frozen sections were stained by the immunoperoxidase method using monoclonal antibody (MoAb) 6.5B5 to identify expression of intercellular adhesion molecule (ICAM-1) and MoAb 1.2B6 for endothelial leucocyte adhesion molecule (ELAM-1). Araldite-embedded sections were also stained for eosinophils using MoAb EG2 to identify eosinophilic cationic protein (ECP). A significant mucosal eosinophilia was apparent in the asthmatic but not in the normal biopsies. Immunostaining for ICAM-1 was observed in both the epithelium and endothelium and ELAM-1 in endothelium, with no significant differences being apparent between the asthmatic and normal subjects. Topical BDP markedly reduced the mucosal eosinophilia without affecting the expression of either adhesion molecule. Using this method, we conclude that there is basal expression of ICAM-1 and ELAM-1 in normal human bronchial mucosa, which is not significantly different from that in asthmatics, and that it is insensitive to suppression with corticosteroids at an inhaled dose that causes clinical improvement.
Neoadjuvant chemotherapy and bladder-sparing surgery for invasive bladder cancer: ten-year outcome.
Authors: H W Herr, D F Bajorin, H I Scher
Journal: Journal of Clinical Oncology (1998)

To evaluate the 10-year outcome of patients with invasive (T2-3N0M0, staged according to the tumor, node, metastasis system) bladder cancer who responded completely to a combination of methotrexate, vinblastine, adriamycin, and cisplatin (MVAC) chemotherapy followed by bladder-sparing surgery.Of 111 surgical candidates who received neoadjuvant MVAC, 60 (54%) achieved a complete clinical response (T0) on transurethral resection (TUR) of the primary tumor site. Of these, 28 requested follow-up with TUR alone, 15 had a partial cystectomy, and 17 elected a radical cystectomy. The patients were followed up for a median of 10 years (range, 8 to 13 years).Of 43 patients who had bladder-sparing surgery, 32 (74%) are alive, which includes 25 (58%) with an intact functioning bladder. Twenty-four patients (56%) developed bladder tumor recurrences from 5 to 96 months, which were invasive in 13 (30%) and superficial in 11 (26%). Thirteen patients required a salvage cystectomy, of whom 6 died, which includes 4 (9%) from a new invasive neoplasm. Of the 17 patients who had radical cystectomy, 11 (65%) are alive.The majority of patients with invasive bladder tumors who achieve T0 status after neoadjuvant MVAC chemotherapy preserve their bladders for up to 10 years with bladder-sparing surgery. The bladder remains at risk for new invasive tumors. Cystectomy salvages the majority, but not all, of relapsing patients.
Electronic cigarettes: Perceptions of doctors working in a large teaching hospital in the UK
Authors: Raghu Raju, Vinod Palissery, Ali Al-Ameri, Doytchin Dimov
Journal: European Respiratory Journal (2014)

Background  Electronic cigarettes (E-cigarettes) are marketed as a smoking cessation method but the overall risks and benefits uncertain. Medical professionals are expected to offer advice regarding E-cigarettes and therefore, this study explored the perception amongst doctors towards the use of E-cigarette by patients.  Methods  An electronic survey was emailed to all doctors in a large teaching hospital in Leeds (United Kingdom). The survey consisted of 10 questions including doctors9 grade and specialty, exposure to patients using E-cigarettes, advice provided and professional perception of E-cigarettes.  Results  146 responses were received. Grades consisted of consultants (37%), specialty registrars (29%) and foundation trainees (25.5%). Main Specialties included medical (39%), surgical (13.6%), anaesthetics (15.5%) and emergency medicine (9%). 70% had come across patients using E-cigarettes occasionally (52%), one to five times a week (41%) or five to ten times a week (6%). 64 doctors (44%) provided advise to patients. The advise was to continue using E-cigarettes, as the intention was smoking cessation (n=13, 20%), to continue using E-cigarettes despite the reason (n=3, 5%), to stop using E-cigarettes (n=9, 14%) or explained they were unable to provide any specific medical advice (n=39, 61%). E-cigarettes were deemed to be safe by 20 (14%) and unsafe by 57 (40%). 67 (46%) admitted lack of knowledge in this regard.  Conclusions  Healthcare professionals are increasingly exposed to patients using E-cigarettes. There is however, a lack of consensus regarding its use and safety with a majority unable to give any specific advice. Research and guidelines in this area are urgently needed.
Outcomes of Advanced Renal Cell Carcinoma Patients (Arcc) Treated with Mammalian Target of Rapamycin Inhibitor (Mtori) Therapy Following First-Line Pazopanib (Paz) in a Us Community Oncology Setting
Authors: T. Hutson, M.D. Hackshaw, N. Vogelzang, D. Bhowmik, M. Yap, D. Rembert, E. Jonasch
Journal: Annals of Oncology (2014)
Breast Cancer Risk From Low-Dose Exposures to Ionizing Radiation: Results of Parallel Analysis of Three Exposed Populations of Women
Authors: C E Land, J D Boice, R E Shore, J E Norman, M Tokunaga
Journal: JNCI Journal of the National Cancer Institute (1980)

Breast cancer incidence data were analyzed from three populations of women exposed to ionizing radiation: survivors of the Hiroshima and Nagasaki atomic bombs, patients in Massachusetts tuberculosis sanitoria who were exposed to multiple chest fluoroscopies, and patients treated by X-rays for acute postpartum mastitis in Rochester, New York. Parallel analyses by radiation dose, age at exposure, and time after exposure suggested that risk of radiation-induced cancer increased approximately linearly with increasing dose and was heavily dependent on age at exposure; however, the risk was otherwise remarkably similar among the three population, at least for age 10-40 years at exposure, and followed the same temporal pattern of occurrence as did breast cancer incidence in nonexposed women of similar ages.
Intrapleural cut of cavity (cut of abscess) with excision of externally walls of cavities and suturing of perforation bronchi under fiber tuberculosis and chronic abscess of lung
Authors: Anatolij Laptev, Irina Orlova
Journal: European Respiratory Journal (2012)

In common chronic processes are often of the standard operations can be applied only Pneumonectomy, the operation of such a large volume in the presence of low functional reserves is a big risk in these cases organsaving operations are preferred.  The object of study is based on 65 patients who had been made on the organsaving operation of various chronic destructive lung disease. Of these, the tuberculosis was observed in 23 people, a chronic abscess - with 16 people, bullous disease - in 23 people, aspergilloma - with 3 people.  The study assessed the efficiency of surgical intervention in the form of intrapleural cut of cavity with suturing draining bronchi.  Application of Intrapleural cut of cavity became possible after the development of techniques for suturing bronchi, draining intrapulmonary cavity (Author9s evidence. No. 1426554 of 1988.).  The Methods of suturing of bronchi, must prevent probability of the origin opening of bronchi, that ligature, overlaying bronchi, turned out to be around wall bronchi directly, at the depth 0,4-0,5 refer to from mouth bronchi.  With the implementation of this type of surgical treatment in 64 patients showed a stable remission of chronic process, without the occurrence of infectious complications. In 1 patients death came as a result of pulmonary embolism.  Organsaving surgical interventions targeting the elimination of the cavity create the conditions for termination of exacerbations.  With the wide application of this type of organsaving operations increases the possibility of improving the quality of life of patients after surgery on the destructive lung disease.
Cost-Effectiveness Analysis of Human Papillomavirus Vaccination in the Netherlands
Authors: I. M. C. M. de Kok, M. van Ballegooijen, J. D. F. Habbema
Journal: JNCI Journal of the National Cancer Institute (2009)

In the Netherlands, low cervical cancer incidence and mortality rates might limit the cost-effectiveness of vaccination against the human papillomavirus (HPV). We examined the effect on cervical cancer incidence and mortality of adding HPV vaccination to the current Dutch cervical cancer screening situation and calculated the cost-effectiveness. Costs and effects were estimated under favorable assumptions (ie, that HPV vaccination provides lifelong protection against 70% of all cervical cancers, has no side effects, and is administered to all women regardless of their risk of cervical cancer) by using the microsimulation screening analysis (MISCAN) model. The impact of changes in the price of vaccination, number of booster vaccinations, vaccination attendance rate, vaccination efficacy, cervical cancer incidence level, and quality-of-life assumptions was investigated in sensitivity analyses. Using the current price of €118 per vaccine dose and with discounting of costs and effects at an annual rate of 3%, adding HPV vaccination to the current Dutch screening situation had a cost-effectiveness ratio of €53 500 per quality-adjusted life-year (QALY) gained. The threshold price per vaccine dose at which the cost-effectiveness of vaccination would correspond to an acceptability threshold of €20 000 per QALY gained was €40. With the addition of one or more (up to four) booster vaccinations during a lifetime, this threshold price decreased to €33 for one booster (to €16 for four boosters). With a doubling of the cervical cancer incidence level, the cost-effectiveness ratio was €24 400 per QALY gained and the maximum price per dose at threshold of €20 000 was €97. All threshold prices were lower under less favorable effectiveness assumptions. In the Netherlands, HPV vaccination is not cost-effective even under favorable assumptions. To become cost-effective, the vaccine price would have to be decreased considerably, depending on the effectiveness of the vaccine.
Second neoplasms in patients with Hodgkin's disease following combined modality therapy--the Yale experience.
Authors: A J Koletsky, J R Bertino, L R Farber, L R Prosnitz, D S Kapp, D Fischer, C S Portlock
Journal: Journal of Clinical Oncology (1986)

From 1969 to 1982, 183 patients with previously untreated stages IIIB and IV Hodgkin's disease and relapsing Hodgkin's disease after radiation therapy were treated with combination chemotherapy plus low-dose irradiation (CRT). One hundred fifty patients who achieved a complete response (CR) were analyzed for risk of developing a second neoplasm. Median follow-up has been 8.3 years. Actuarial survival of all patients is 74% at 10 years with a relapse-free survival of 68%. An additional 24 patients with stage IIIA disease were also treated with CRT. There were 22 CRs at risk who were analyzed. Median follow-up has been 3+ years with an actuarial survival of 90% at five years and a relapse-free survival of 83%. Second neoplasms have developed in 14 of 172 patients at risk: acute nonlymphocytic leukemia (ANLL; five patients); aggressive histology non-Hodgkin's lymphoma (NHL; three patients); and a variety of solid neoplasms (six patients). Time to second neoplasm diagnosis after initial treatment ranged from 12 to 141 months. Five patients were older than 40 years. At the time of diagnosis of the second malignancy, 11 patients were free of Hodgkin's disease (for 36 to 141 months) and three were receiving therapy for recurrent Hodgkin's disease. The 10-year actuarial risk (%) of developing ANLL was 5.9 +/- 2.8; for NHL, the risk was 3.5 +/- 2.4, and for solid neoplasms, 5.8 +/- 3.0. Our results suggest that combination chemotherapy plus low-dose irradiation does not appear to significantly increase the risk of developing second neoplasms above that already reported for combination chemotherapy when administered as either initial or salvage treatment of Hodgkin's disease.
Malignant Transformation of Rat Liver Cells by &lt;italic&gt;N&lt;/italic&gt;-Benzoyloxy-3′-methyl-4-methylaminoazobenzene and its Related Compound&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: T Tokiwa, T Hishinuma, M Degawa, Y Hashimoto, J Sato
Journal: JNCI Journal of the National Cancer Institute (1986)

N-Benzoyloxy-3'-methyl-4-methylaminoazobenzene-(N-benzoyloxy-3'-Me-MAB) was highly toxic to rat liver epithelial cells (Ac2F) and induced many more chromosome aberrations and unscheduled DNA synthesis than did 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB). N-Benzoyloxy-3'-Me-MAB and its related compound, N-acetoxy-4-methylaminoazobenzene, efficiently induced malignant transformation of the cells, but 3'-Me-DAB was not so effective. The cells transformed by N-acyloxy-4-methylaminoazobenzene (N-acyloxy-MAB) derivatives showed significant increases in plating efficiency in liquid medium and in the size of aggregates in rotation culture. Such increases were not seen in the 3'-Me-DAB-transformed cells. The results indicate that the N-acyloxy form of the 4-dimethylaminobenzene derivatives seems very likely to be the ultimate metabolite.
Genome-Wide Dosage-Dependent and -Independent Regulation Contributes to Gene Expression and Evolutionary Novelty in Plant Polyploids
Authors: Xiaoli Shi, Changqing Zhang, Dae Kwan Ko, Z. Jeffrey Chen
Journal: Molecular Biology and Evolution (2015)

Polyploidy provides evolutionary and morphological novelties in many plants and some animals. However, the role of genome dosage and composition in gene expression changes remains poorly understood. Here, we generated a series of resynthesized Arabidopsis tetraploids that contain 0–4 copies of Arabidopsis thaliana and Arabidopsis arenosa genomes and investigated ploidy and hybridity effects on gene expression. Allelic expression can be defined as dosage dependent (expression levels correlate with genome dosages) or otherwise as dosage independent. Here, we show that many dosage-dependent genes contribute to cell cycle, photosynthesis, and metabolism, whereas dosage-independent genes are enriched in biotic and abiotic stress responses. Interestingly, dosage-dependent genes tend to be preserved in ancient biochemical pathways present in both plant and nonplant species, whereas many dosage-independent genes belong to plant-specific pathways. This is confirmed by an independent analysis using Arabidopsis phylostratigraphic map. For A. thaliana loci, the dosage-dependent alleles are devoid of TEs and tend to correlate with H3K9ac, H3K4me3, and CG methylation, whereas the majority of dosage-independent alleles are enriched with TEs and correspond to H3K27me1, H3K27me3, and CHG (H = A, T, or C) methylation. Furthermore, there is a parent-of-origin effect on nonadditively expressed genes in the reciprocal allotetraploids especially when A. arenosa is used as the pollen donor, leading to metabolic and morphological changes. Thus, ploidy, epigenetic modifications, and cytoplasmic-nuclear interactions shape gene expression diversity in polyploids. Dosage-dependent expression can maintain growth and developmental stability, whereas dosage-independent expression can facilitate functional divergence between homeologs (subfunctionalization and/or neofunctionalization) during polyploid evolution.
A case–control study: Association between serum neuregulin 4 level and non-alcoholic fatty liver disease
Authors: Yi-Ning Dai, Jin-Zhou Zhu, Zhi-Yun Fang, De-Jian Zhao, Xing-Yong Wan, Hua-Tuo Zhu, Chao-Hui Yu, You-Ming Li
Journal: Metabolism (2015)