tbuckley/cabot-search huggingface dataset:
Cancer Incidence Among Pesticide Applicators Exposed to Atrazine in the Agricultural Health Study
Authors: J. A. Rusiecki, A. De Roos, W. J. Lee, M. Dosemeci, J. H. Lubin, J. A. Hoppin, A. Blair, M. C. R. Alavanja
Journal: JNCI Journal of the National Cancer Institute (2004)

Background: Atrazine is the most heavily applied agricultural pesticide for crop production in the United States. Both animal and human studies have suggested that atrazine is possibly carcinogenic, but results have been mixed. We evaluated cancer incidence in atrazine-exposed pesticide applicators among 53 943 participants in the Agricultural Health Study, a prospective cohort study of licensed pesticide applicators in Iowa and North Carolina. Methods: We obtained detailed pesticide exposure information using a self-administered questionnaire completed at the time of enrollment (1993–1997). Cancer incidence was followed through December 31, 2001. We used adjusted Poisson regression to calculate rate ratios (RRs) and 95% confidence intervals (CIs) of multiple types of cancer among atrazine exposed applicators. Ptrend values were calculated using atrazine exposure as a continuous variable, and all statistical tests were two-sided. Two exposure metrics were used: quartiles of lifetime days of exposure and quartiles of intensity-weighted lifetime days of exposure. Results: 36 513 (68%) applicators reported ever using atrazine; exposure was not associated with overall cancer incidence. Comparisons of cancer incidence in applicators with the highest atrazine exposure and those with the lowest exposure, assessed by lifetime days (RR LD ) and intensity-weighted lifetime days (RR IWLD ) of exposure yielded the following results: prostate cancer, RR LD = 0.88, 95% CI = 0.63 to 1.23, Ptrend = .26, and RR IWLD = 0.89, 95% CI = 0.63 to 1.25, Ptrend = .35; lung cancer, RR LD = 1.91, 95% CI = 0.93 to 3.94, Ptrend = .08, and RR IWLD = 1.37, 95% CI = 0.65 to 2.86, Ptrend = .19; bladder cancer, RR LD = 3.06, 95% CI = 0.86 to 10.81, Ptrend =.18, and RR IWLD = 0.85, 95% CI = 0.24 to 2.94, Ptrend = .71; non-Hodgkin lymphoma, RR LD = 1.61, 95% CI = 0.62 to 4.16, Ptrend = .35, and RR IWLD = 1.75, 95% CI = 0.73 to 4.20, Ptrend = .14; and multiple myeloma, RR LD = 1.60, 95% CI = 0.37 to 7.01, Ptrend = .41, and RR IWLD = 2.17, 95% CI = 0.45 to 10.32, Ptrend = .21. Conclusions: Our analyses did not find any clear associations between atrazine exposure and any cancer analyzed. However, further studies are warranted for tumor types in which there was a suggestion of trend (lung, bladder, non-Hodgkin lymphoma, and multiple myeloma).
(20) Vinyl chloride disease
Authors: E.N. Mitchell Johnston
Journal: British Journal of Dermatology (1978)

Journal Article (20) Vinyl chloride disease Get access E.N. Mitchell Johnston E.N. Mitchell Johnston General Hospital, Nottingham Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 99, Issue s16, 1 December 1978, Pages 45–48, https://doi.org/10.1111/j.1365-2133.1978.tb15242.x Published: 01 December 1978
RhoC Promotes Metastasis via Activation of the Pyk2 Pathway in Prostate Cancer
Authors: Megumi Iiizumi, Sucharita Bandyopadhyay, Sudha K. Pai, Misako Watabe, Shigeru Hirota, Sadahiro Hosobe, Taisei Tsukada, Kunio Miura, Ken Saito, Eiji Furuta, Wen Liu, Fei Xing, Hiroshi Okuda, Aya Kobayashi, Kounosuke Watabe
Journal: Cancer Research (2008)

Abstract RhoC is a member of the Ras-homologous family of genes which have been implicated in tumorigenesis and tumor progression. However, the exact role of RhoC is controversial and is yet to be clarified. We have examined the effect of RhoC on prostate tumor cells and found that RhoC had no effect on cell proliferation in vitro or on tumor growth in mice. However, RhoC significantly enhanced the metastatic ability of the tumor cells in these animals, suggesting that RhoC affects only the metastasis but not the growth of prostate tumor cells. The results of our immunohistochemical analyses on tumor specimens from 63 patients with prostate cancer indicate that RhoC expression had no significant correlation with Gleason grade. However, the expression of RhoC showed significant positive correlation with both lymph node and distant metastasis, and it was inversely correlated with patient survival. We also found that RhoC significantly augmented the invasion and motility of prostate tumor cells by activating matrix metalloproteinases 2 and 9 (MMP2 and MMP9) in vitro. The results of our antibody array analysis for signal molecules revealed that RhoC significantly activated kinases including mitogen-activated protein kinase (MAPK), focal adhesion kinase (FAK), Akt, and Pyk2. Inhibition of Pyk2 kinase blocked the RhoC-dependent activation of FAK, MAPK, and Akt, followed by the suppression of MMP2 and MMP9. Inhibitors of both MAPK and Akt also significantly blocked the activities of these MMPs. Therefore, our results indicate that RhoC promotes tumor metastasis in prostate cancer by sequential activation of Pyk2, FAK, MAPK, and Akt followed by the up-regulation of MMP2 and MMP9, which results in the stimulation of invasiveness of tumor cells. [Cancer Res 2008;68(18):7613–20]
Impact of Follow-up Testing on Survival and Health-Related Quality of Life in Breast Cancer Patients
Authors: P. Ghezzi
Journal: JAMA (1994)

To assess prospectively the impact on survival and health-related quality of life of two follow-up protocols in patients with early breast cancer.Randomized controlled clinical trial.Multicenter study involving 26 general hospitals in Italy.A consecutive sample of 1320 women younger than 70 years with stage I, II, and III unilateral primary breast cancer.Patients were randomly assigned to an intensive surveillance, which included physician visits and performance of bone scan, liver echography, chest roentgenography, and laboratory tests at predefined intervals (n = 655), or to a control regimen (n = 665), in which patients were seen by their physicians at the same frequency but only clinically indicated tests were performed. Both groups received a yearly mammogram aimed at detecting contralateral breast cancer.Primary end points were overall survival and health-related quality of life.Compliance to the two follow-up protocols was more than 80%. At a median follow-up of 71 months, no difference was apparent in overall survival with 132 deaths (20%) in the intensive group and 122 deaths (18%) in the control group. No significant differences were apparent in time to detection of recurrence between the two groups. Measurements of health-related quality of life (ie, overall health and quality-of-life perception, emotional well-being, body image, social functioning, symptoms, and satisfaction with care) at 6, 12, 24, and 60 months of follow-up did not show differences by type of care received.Results of this trial support the view that a protocol of frequent laboratory tests and roentgenography after primary treatment for breast cancer does not improve survival or influence health-related quality of life. Routine use of these tests should be discouraged.
The impact of a specialist multi-disciplinary approach on burden of frequent asthma admissions
Authors: Jenny Davis, Andrew Tan, Sian Evans, Laura Flowers, Hannah Burke, Ramesh Kurukulaaratchy
Journal: European Respiratory Journal (2014)

Background:  While only 10% of asthmatics have “Difficult Asthma” they account for 80% of asthma-related expenditure and run the highest risk of acute severe exacerbations. An estimated 75% of admissions for asthma are avoidable. Guidelines advise that patients with “Difficult Asthma” are managed by an experienced specialist multidisciplinary team (MDT).   Aim:  To assess the impact of a case-management strategy delivered via specialist MDT on acute healthcare utilization of patients with frequent asthma admissions.   Method:  An MDT (consultant, specialist nurse, physiotherapist and psychologist) case-management strategy was introduced in 2010 at Southampton General Hospital (Southampton, United Kingdom) to support patients with frequent asthma admissions during admission and then in clinic. To assess efficacy, we systematically searched the hospital database for patients acutely admitted for asthma on ≥2 occasions in 2010, 2011 and 2012. Data were collected retrospectively covering patient demographics, admission details, asthma severity, and co-morbidity.   Results:  From 2010-2012 83 patients were admitted on ≥ 2 occasions per year (79% female, 52% BMI>30, 57% psychological co-morbidity). After introducing an MDT approach repeat asthma admission rate fell by 33% from 127 per year in 2010 to 84 in 2012 (p=0.057). Bed days also fell by 52% from 895 per year in 2010 to 430 in 2012. The number of cases per year was constant as were the number of cases who featured in only 1 year. Only 2 patients were admitted on 2 or more occasions in 2010, 2011 and 2012.   Conclusion:  An MDT case-management approach significantly reduces hospitalization in Difficult Asthma patients with prior frequent admission.
ELECTROPHORETIC STUDIES ON ELEMENTARY BODIES OF VACCINIA
Authors: Theodore Shedlovsky, Joseph E. Smadel
Journal: The Journal of Experimental Medicine (1940)

Electrophoretic studies were made on vaccine virus, collodion particles, and glass particles suspended in 0.01 molar buffer solutions at pH 7.9, in which the moving boundary method was used. In some experiments, uncoated particles were used; in others, particles were coated with proteins and then resuspended in the buffer solution after a washing; in still others, an excess of protein which had been used to coat the particles was included in the buffer medium. Streaming boundaries were obtained with all dilute suspensions of particles in solutions containing no soluble protein instead of the flat ones usually observed with the Tiselius moving boundary technique. This boundary artifact was suppressed by maintaining a density gradient of sufficient magnitude in association with the moving boundary to counteract the tendency of endosmotic flow. This was done partially by increasing the concentration of the particles in the suspensions, and almost completely by retaining an excess of soluble-coating substance in the solutions containing the particles. The mobility of elementary bodies of vaccinia corresponds to that found for the heat-stable (S) antigen. This value was not altered by drying, heating, ether extraction, or simple washing, but was materially increased by treatment with the surface active detergent (duponol) which presumably altered the nature of the surface of the virus particles. Collodion particles coated with the heat-stable antigen of vaccinia had the same mobility as elementary bodies under comparable conditions. Glass particles coated with normal rabbit serum moved at the rate of albumin, the fastest serum component in the buffer solutions used. However, both collodion particles and vaccine virus moved at a somewhat slower rate when they were similarly coated and measured in the presence of an excess of serum in the solutions. This was probably due to adsorption of a small amount of one of the slower components (globulin) of rabbit serum on the surface of the particles. Simple washing after treatment seemed to remove the coating of serum proteins, at least in part, from both collodion particles and elementary bodies of vaccinia.
Endothelial cell cytotoxicity in inflammatory vascular diseases--the possible role of oxidised lipoproteins.
Authors: D R Blake, P Winyard, D G Scott, S Brailsford, A Blann, J Lunec
Journal: Annals of the Rheumatic Diseases (1985)

One of the proposed mechanisms of vascular damage in connective tissue disease is the direct action of a cytotoxic serum factor inducing endothelial cell damage. The nature of this serum factor is unclear, but has been suggested to be a lipoprotein. Sera from patients with (1) systemic necrotising arteritis (polyarteritis nodosa, Wegener9s granulomatosis, and necrotising arteritis associated with rheumatoid synovitis), (2) systemic or joint restricted rheumatoid disease, and (3) large vessel/giant cell arteritis have been examined for cytotoxicity to human cultured endothelial cells and azide-resistant ferroxidase-like activity (indicative of the oxidised lipoprotein content). Stored sera from patients with necrotising arteritis showed a significantly enhanced tendency to develop oxidised lipoprotein, which correlated closely with human endothelial cell cytotoxicity. Fresh sera also contained this factor, but to a lesser extent. It is argued that the cytotoxic factor detected in previous clinical studies is in part an in-vitro artefact, although its accelerated development in certain patient groups might suggest an excess of pro-oxidants that have developed in vivo.
Combining Radiotherapy and Cancer Immunotherapy: A Paradigm Shift
Authors: Silvia C. Formenti, Sandra Demaria
Journal: JNCI Journal of the National Cancer Institute (2013)

The therapeutic application of ionizing radiation has been largely based on its cytocidal power combined with the ability to selectively target tumors. Radiotherapy effects on survival of cancer patients are generally interpreted as the consequence of improved local control of the tumor, directly decreasing systemic spread. Experimental data from multiple cancer models have provided sufficient evidence to propose a paradigm shift, whereby some of the effects of ionizing radiation are recognized as contributing to systemic antitumor immunity. Recent examples of objective responses achieved by adding radiotherapy to immunotherapy in metastatic cancer patients support this view. Therefore, the traditional palliative role of radiotherapy in metastatic disease is evolving into that of a powerful adjuvant for immunotherapy. This combination strategy adds to the current anticancer arsenal and offers opportunities to harness the immune system to extend survival, even among metastatic and heavily pretreated cancer patients. We briefly summarize key evidence supporting the role of radiotherapy as an immune adjuvant. A critical appraisal of the current status of knowledge must include potential immunosuppressive effects of radiation that can hamper its capacity to convert the irradiated tumor into an in situ, individualized vaccine. Moreover, we discuss some of the current challenges to translate this knowledge to the clinic as more trials testing radiation with different immunotherapies are proposed.
TopBP1 and Claspin contribute to the radioresistance of lung cancer brain metastases
Authors: Seung Ho Choi, Heekyoung Yang, Seung Ho Lee, Joo-Hyun Ki, Do-Hyun Nam, Hae Yong Yoo
Journal: Molecular Cancer (2014)

Radiation therapy is one of the most effective therapeutic tools for brain metastasis. However, it is inevitable that some cancer cells become resistant to radiation. This study is focused on the identification of genes associated with radioresistance in metastatic brain tumor from lung cancer and the functional examination of the selected genes with regards to altered sensitivity of cancer cells to radiation. After establishing radioresistant cells from the xenograft model, we explored the significant transcriptional changes by performing DNA microarray profiling. Functional analyses in vitro and in vivo performed to validate the gene responsible for radioresistance. Transcriptional changes induced by radiation therapy are much more extensive in H460 cells than in PC14PE6 cells. The expression levels of TopBP1 and Claspin were increased in the cancer cells that survived radiation therapy. Depletion of TopBP1 or Claspin using shRNA showed an enhancement of sensitivity to radiation in radioresistant lung cancer cells (PC14PE6). Moreover, increased levels of TopBP1 or Claspin endowed cells a higher resistance to radiation. In xenograft models, the knock-down of TopBP1 or Claspin significantly prolonged the median survival time post radiation therapy. We analyzed the gene expression profiles of the radiosensitive cells and the radioresistant cells to define a set of genes that may be involved in endowing lung cancer cells radioresistance post brain metastasis. Functional analyses indicated that the expression TopBP1 and Claspin positively affects the survival of cancer cells and thus negatively the xenograft metastasis model animals in response to radiation. These results show that TopBP1 and Claspin can be potential targets for the enhanced efficacy of radiotherapy.
Identification of Prognostic Biomarkers for Prostate Cancer
Authors: Farhad Kosari, Jan Marie A. Munz, C. Dilara Savci-Heijink, Craig Spiro, Eric W. Klee, Dagmar Marie Kube, Lori Tillmans, Jeff Slezak, R. Jeffrey Karnes, John C. Cheville, George Vasmatzis
Journal: Clinical Cancer Research (2008)

Abstract Purpose: This paper describes a process for the identification of genes that can report on the aggressiveness of prostate tumors and thereby add to the information provided by current pathologic analysis. Materials and Methods: Expression profiling data from over 100 laser capture microdissection derived samples from nonneoplastic epithelium; Gleason patterns 3, 4, and 5 and node metastasis prostate cancer were used to identify genes at abnormally high levels in only some tumors. These variably overexpressed genes were stratified by their association with aggressive phenotypes and were subsequently filtered to exclude genes with redundant expression patterns. Selected genes were validated in a case-control study in which cases (systemic progression within 5 years) and controls (no systemic progression at 7 years of follow-up) were matched for all clinical and pathologic criteria from time of prostatectomy (n = 175). Both cases and controls, therefore, could have nodal invasion or seminal vesicle involvement at the time of initial treatment. Results: A number of candidate variably overexpressed genes selected for their association with aggressive prostate cancer phenotype were evaluated in the case control study. The most prominent candidates were SSTR1 and genes related to proliferation, including TOP2A. Conclusions: The process described here identified genes that add information not available from current clinical measures and can improve the prognosis of prostate cancer.
Sequential tubular cell and basement membrane changes in polycystic kidney disease.
Authors: F A Carone, S Nakamura, P Punyarit, Y S Kanwar, W J Nelson
Journal: Journal of the American Society of Nephrology (1992)

Tubular basement membrane (BM) changes (dysmorphogenesis), cell proliferation, and fluid accumulation related to the altered location of Na,K-ATPase are purported essential key events in the development and progression of renal cysts. These changes were assessed daily in Phenol II (2-amino-4-hydroxyphenyl-5-phenyl thiazole)-treated rats, which rapidly develop marked and progressive cystic change of all collecting tubules (CT). At Day 1, 12% of CT were cystic and their BM were thickened severalfold. At Day 4, 30% of CT were cystic and their BM remained thickened. BM of cystic tubules showed decreased staining for heparan sulfate proteoglycan and increased staining for fibronectin. Proliferation, as determined by (3H)thymidine, incorporation, was not significant until Day 2 and involved cystic and noncystic tubular cells as well as interstitial cells. As cystic changes progressed, cell proliferation decreased. By immunohistochemistry, the altered location of Na,K-ATPase in epithelial cells lining cysts was primarily detected after Day 2 and consisted of focal loss from basal and/or lateral cell membranes and localization in the cell cytoplasm. Only rarely was Na,K-ATPase localized to the apical cell membrane. After the removal of Phenol II, cystic tubular cells, BM, and Na,K-ATPase returned to normal. Thus, in this model of polycystic kidney disease, initial cyst formation occurred in tandem with BM structural change whereas cell proliferation and altered location of Na,K-ATPase occurred after the appearance of cysts.
Modulation of the acute respiratory effects of winter air pollution by serum and dietary antioxidants: a panel study
Authors: L Grievink, SC van der Zee, G Hoek, HM Boezen, P van't Veer, B Brunekreef
Journal: European Respiratory Journal (1999)

This study investigated whether a high dietary intake or serum concentration of antioxidant (pro-) vitamins could attenuate the acute respiratory effects of air pollution in panels of adults (n = 227) aged 50-70 yrs with chronic respiratory symptoms in two winters starting in 1993/1994. Subjects performed daily peak expiratory flow (PEF) measurements in the morning and evening and reported the occurrence of respiratory symptoms in two regions (urban and nonurban) each winter. Logistic regression analysis was used with the prevalences of large PEF decrements as dependent variables and air pollution levels as independent variables. Analyses were performed separately for subjects below and above the median levels of serum beta-carotene and the intake of dietary vitamin C and beta-carotene. Subjects with low levels of serum beta-carotene more often had large PEF decrements when particles &lt;10 microm in diameter or black smoke levels which were higher compared to subjects with high levels of serum beta-carotene. The same results tended to be observed for dietary vitamin C or beta-carotene, but there were less significant air pollution effects in the low dietary antioxidant group. The results suggest that serum beta-carotene and to a lesser extent dietary vitamin C and beta-carotene may attenuate peak expiratory flow decrements due to air pollution in subjects with chronic respiratory symptoms.
Activation of Epithelial Sodium Channels by Mouse Channel Activating Proteases (mCAP) Expressed in Xenopus Oocytes Requires Catalytic Activity of mCAP3 and mCAP2 but not mCAP1
Authors: Ditte Andreasen, Gre[Combining Acute Accent]goire Vuagniaux, Nicole Fowler-Jaeger, Edith Hummler, Bernard C. Rossier
Journal: Journal of the American Society of Nephrology (2006)

Mouse channel activating proteases 1, 2, and 3 (mCAP1, mCAP2, and mCAP3) were described recently as regulators of the epithelial sodium channel (ENaC). The mCAP are membrane-bound serine proteases that are synthesized as inactive proenzymes. To mature into active proteases, they undergo intramolecular cleavage by auto- and/or heterocatalytic processing. Specific antibodies against each mCAP were developed to distinguish between proenzyme and active protease by Western blot analysis. Various point mutations were introduced in the catalytic or protein-protein interacting domains of mCAP and wild-type and mutant enzymes were expressed in the Xenopus oocyte expression system to test for ability to activate ENaC. In mCAP3, an intact catalytic triad was necessary for activation of ENaC but not for intramolecular cleavage of the protease. This suggests a heterocatalytic mechanism. Mutating the catalytic triad of mCAP2 not only abolished ENaC activation completely but also impeded cleavage of the protease. Processing of mCAP2 therefore seems to be autocatalytic. Furthermore, mutations in conserved residues of mCAP2 located in two protein-protein interacting domains significantly modulated ENaC activation. Surprisingly, mCAP1 catalytically inactive mutants were still able to fully activate ENaC, and no evidence of mCAP1 intramolecular cleavage was seen. The presence of an intact glycosylphosphatidylinositol anchor, however, was required. It is concluded that auto- and heterocatalytic requirements are specific for each CAP and that endogenous partners are a necessity for activation of ENaC by mCAP in the Xenopus oocyte expression system.