tbuckley/cabot-search huggingface dataset:
Sequence Variants of<b><i>Toll-Like Receptor 4</i></b>Are Associated with Prostate Cancer Risk
Authors: S. Lilly Zheng, Katarina Augustsson-Bälter, Baoli Chang, Maria Hedelin, Liwu Li, Hans-Olov Adami, Jeanette Bensen, Ge Li, Jan-Erik Johnasson, Aubrey R. Turner, Tamara S. Adams, Deborah A. Meyers, William B. Isaacs, Jianfeng Xu, Henrik Grönberg
Journal: Cancer Research (2004)

Abstract Inflammation has been implicated as an etiological factor in several human cancers. Growing evidence suggests that chronic inflammation may also play a role in the etiology of prostate cancer. Considering that genetic susceptibility is a major risk factor for this disease, we hypothesize that sequence variants in genes that regulate inflammation may modify individual susceptibility to prostate cancer. The lipopolysaccharide receptor Toll-like receptor 4 (TLR4) is a central player in the signaling pathways of the innate immune response to infection by Gram-negative bacteria and is an important candidate inflammatory gene. We performed a systematic genetic analysis of TLR4 sequence variants by evaluating eight single-nucleotide polymorphisms that span the entire gene among 1383 newly diagnosed prostate cancer patients and 780 age- and residence-matched controls in Sweden. We found an association between a sequence variant (11381G/C) in the 3′-untranslated region of the TLR4 gene and prostate cancer risk. The frequency of the variant genotypes (CG or CC) was significantly higher in the patients (24.1%) than in the controls (19.7%; P = 0.02). The frequency of risk genotypes among patients diagnosed before the age of 65 years was even higher (26.3%). Compared with men who had the wild-type genotype of this single-nucleotide polymorphism (GG), those with GC or CC genotypes had a 26% increased risk for prostate cancer (odds ratio, 1.26; 95% confidence interval, 1.01–1.57) and 39% increased risk increased risk for early onset prostate cancer (before age 65 years; odds ratio, 1.39; 95% confidence interval, 1.02–1.91). The risk attributable to this variant for prostate cancer in Sweden was estimated to be 4.9%. Although the biological mechanism of the observed association remains to be elucidated, our finding supports a role for a bacteria-associated response pathway, possibly acting via inflammation, in the development of prostate cancer.
Primary malignant melanomas of cervix uteri and vulva
Authors: A. Butt, D.L. Roberts, J.P. Calvert, S. Williams
Journal: British Journal of Dermatology (1996)

Journal Article Primary malignant melanomas of cervix uteri and vulva Get access A. Butt, A. Butt Department of Dermatology, Singleton Hospital, Sketty, Swansea, U.K. Search for other works by this author on: Oxford Academic Google Scholar D.L. Roberts, D.L. Roberts Department of Dermatology, Singleton Hospital, Sketty, Swansea, U.K. Search for other works by this author on: Oxford Academic Google Scholar J.P. Calvert, J.P. Calvert Gynaecology and Obstetrics Department, Singleton Hospital, Sketty, Swansea, U.K. Search for other works by this author on: Oxford Academic Google Scholar S. Williams S. Williams Pathology Department, Singleton Hospital, Sketty, Swansea, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 135, Issue 5, 1 November 1996, Pages 858–859, https://doi.org/10.1111/j.1365-2133.1996.tb03908.x Published: 01 November 1996
Couples coping with COPD: exploring (dis)similarity between patients’ and spouses’ psychosocial adjustment
Authors: Daniela Figueiredo, Joana Cruz, Cristina Jácome, Raquel Gabriel, Alda Marques
Journal: European Respiratory Journal (2014)

Being diagnosed and treated for COPD is often associated with emotional distress. Evidence suggests that spouses play a major role in determining patient9s psychosocial adjustment. Yet, much less is known about partners9 adjustment to COPD demands. This study aimed to explore and compare patients9 and spouses9 psychosocial adjustment to COPD.  A cross-sectional study with a convenience sample was conducted. Socio-demographic data were collected. Psychosocial adjustment was evaluated in seven life domains by the Psychosocial Adjustment to Illness Scale - Self-Report (PAIS-SR). Depression, Anxiety and Stress Scales (DASS) were used to assess emotional status. In both scales, higher scores indicate greater disturbance. Descriptive and inferential analyses were performed.  Twenty five dyads of patients with COPD (66.1±9.2yrs, FEV 1  53.6±18.5pp) and spouses (63.6±8.7yrs) have participated. Spouses reported more problems in overall psychosocial adjustment (23.9±12.1 vs. 31.6±11.8, p=.042) and psychological distress (6.3±2.6 vs. 3.7±2.8; p=.004). Health care orientation was the life domain with the highest scores in both patients (7.0±2.9) and spouses (8.8±3.3, p=.060). Spouses presented higher levels of depressive (9.6±7.7 vs. 5.4±5.1, p=.027) and stress (14.2±7.5 vs. 9.7±6.5, p=.028) symptoms than patients. High levels of anxiety symptoms were found for both patients and spouses (8.9±5.5 vs. 9.6±6.5, p=.676).  Findings suggest that COPD can result in considerable emotional distress for marital couples, in particular, for spouses. Recognising COPD as a family disease is crucial to the development of family-based supportive interventions that can improve couples9 healthy adjustment.
231 Terlipressin and albumin therapy for patients with advanced cirrhosis and severe renal failure
Authors: M. Serrano, J.M. Pascasio, J.M. Sousa, E. De la Santa, M. Sayago, M.T. Ferrer, J.L. Márquez, M. Garzón, T. Grilo, M. Cabanillas
Journal: Journal of Hepatology (2006)
HIF Induces Human Embryonic Stem Cell Markers in Cancer Cells
Authors: Julie Mathieu, Zhan Zhang, Wenyu Zhou, Amy J. Wang, John M. Heddleston, Claudia M.A. Pinna, Alexis Hubaud, Bradford Stadler, Michael Choi, Merav Bar, Muneesh Tewari, Alvin Liu, Robert Vessella, Robert Rostomily, Donald Born, Marshall Horwitz, Carol Ware, C. Anthony Blau, Michele A. Cleary, Jeremy N. Rich, Hannele Ruohola-Baker
Journal: Cancer Research (2011)

Low oxygen levels have been shown to promote self-renewal in many stem cells. In tumors, hypoxia is associated with aggressive disease course and poor clinical outcomes. Furthermore, many aggressive tumors have been shown to display gene expression signatures characteristic of human embryonic stem cells (hESC). We now tested whether hypoxia might be responsible for the hESC signature observed in aggressive tumors. We show that hypoxia, through hypoxia-inducible factor (HIF), can induce an hESC-like transcriptional program, including the induced pluripotent stem cell (iPSC) inducers, OCT4, NANOG, SOX2, KLF4, cMYC, and microRNA-302 in 11 cancer cell lines (from prostate, brain, kidney, cervix, lung, colon, liver, and breast tumors). Furthermore, nondegradable forms of HIFα, combined with the traditional iPSC inducers, are highly efficient in generating A549 iPSC-like colonies that have high tumorigenic capacity. To test potential correlation between iPSC inducers and HIF expression in primary tumors, we analyzed primary prostate tumors and found a significant correlation between NANOG-, OCT4-, and HIF1α-positive regions. Furthermore, NANOG and OCT4 expressions positively correlated with increased prostate tumor Gleason score. In primary glioma-derived CD133 negative cells, hypoxia was able to induce neurospheres and hESC markers. Together, these findings suggest that HIF targets may act as key inducers of a dynamic state of stemness in pathologic conditions.
Mitigating Age-Related Immune Dysfunction Heightens the Efficacy of Tumor Immunotherapy in Aged Mice
Authors: Vincent Hurez, Benjamin J. Daniel, Lishi Sun, Ai-Jie Liu, Sara M. Ludwig, Mark J. Kious, Suzanne R. Thibodeaux, Srilakshmi Pandeswara, Kruthi Murthy, Carolina B. Livi, Shawna Wall, Michael J. Brumlik, Tahiro Shin, Bin Zhang, Tyler J. Curiel
Journal: Cancer Research (2012)

Although cancer tends to affect the elderly, most preclinical studies are carried out in young subjects. In this study, we developed a melanoma-specific cancer immunotherapy that shows efficacy in aged but not young hosts by mitigating age-specific tumor-associated immune dysfunction. Both young and aged CD4(+)CD25(hi) regulatory T cells (Treg) exhibited equivalent in vitro T-cell suppression and tumor-associated augmentation in numbers. However, denileukin diftitox (DT)-mediated Treg depletion improved tumor-specific immunity and was clinically effective only in young mice. DT-mediated Treg depletion significantly increased myeloid-derived suppressor cell (MDSC) numbers in aged but not young mice, and MDSC depletion improved tumor-specific immunity and reduced tumor growth in aged mice. Combining Treg depletion with anti-Gr-1 antibody was immunologically and clinically more efficacious than anti-Gr-1 antibody alone in aged B16-bearing mice, similar to Treg depletion alone in young mice. In contrast, DT increased MDSCs in young and aged mice following MC-38 tumor challenge, although effects were greater in aged mice. Anti-Gr-1 boosted DT effects in young but not aged mice. Aged antitumor immune effector cells are therefore competent to combat tumor when underlying tumor-associated immune dysfunction is appropriately mitigated, but this dysfunction varies with tumor, thus also varying responses to immunotherapy. By tailoring immunotherapy to account for age-related tumor-associated immune dysfunctions, cancer immunotherapy for aged patients with specific tumors can be remarkably improved.
Comparative Effectiveness of a Multifaceted Intervention to Improve Adherence to Annual Colorectal Cancer Screening in Community Health Centers
Authors: David W. Baker, Tiffany Brown, David R. Buchanan, Jordan Weil, Kate Balsley, Lauren Ranalli, Ji Young Lee, Kenzie A. Cameron, M. Rosario Ferreira, Quinn Stephens, Shira N. Goldman, Alred Rademaker, Michael S. Wolf
Journal: JAMA Internal Medicine (2014)

Colorectal cancer (CRC) screening rates are lower among Latinos and people living in poverty. Fecal occult blood testing (FOBT) is one recommended screening modality that may overcome cost and access barriers. However, the ability of FOBT to reduce CRC mortality depends on high rates of adherence to annual screening.To determine whether a multifaceted intervention increases adherence to annual FOBT compared with usual care.Patient-level randomized controlled trial conducted in a network of community health centers. Included were 450 patients who had previously completed a home FOBT from March 2011 through February 2012 and had a negative test result: 72% of participants were women; 87% were Latino; 83% stated that Spanish was their preferred language; and 77% were uninsured.Usual care at participating health centers included computerized reminders, standing orders for medical assistants to give patients home fecal immunochemical tests (FIT), and clinician feedback on CRC screening rates. The intervention group also received (1) a mailed reminder letter, a free FIT with low-literacy instructions, and a postage-paid return envelope; (2) an automated telephone and text message reminding them that they were due for screening and that a FIT was being mailed to them; (3) an automated telephone and text reminder 2 weeks later for those who did not return the FIT; and (4) personal telephone outreach by a CRC screening navigator after 3 months.Completion of FOBT within 6 months of the date the patient was due for annual screening.Intervention patients were much more likely than those in usual care to complete FOBT (82.2% vs 37.3%; P < .001). Of the 185 intervention patients completing screening, 10.2% completed prior to their due date (intervention was not given), 39.6% within 2 weeks (after initial intervention), 24.0% within 2 to 13 weeks (after automated call/text reminder), and 8.4% between 13 and 26 weeks (after personal call).This intervention greatly increased adherence to annual CRC screening; most screenings were achieved without personal calls. It is possible to improve annual CRC screening for vulnerable populations with relatively low-cost strategies that are facilitated by health information technologies.clinicaltrials.gov Identifier: NCT01453894.
Circulating tumour cells early predict progression-free and overall survival in advanced colorectal cancer patients treated with chemotherapy and targeted agents
Authors: J. Tol, M. Koopman, M.C. Miller, A. Tibbe, A. Cats, G.J.M. Creemers, A.H. Vos, I.D. Nagtegaal, L.W.M.M. Terstappen, C.J.A. Punt
Journal: Annals of Oncology (2009)
Development and Future of the American Society of Clinical Oncology's Quality Oncology Practice Initiative
Authors: Douglas W. Blayney, Kristen McNiff, Peter D. Eisenberg, Terry Gilmore, Paul B. Jacobsen, Joseph O. Jacobson, Pamela J. Kadlubek, Michael N. Neuss, Joseph Simone
Journal: Journal of Clinical Oncology (2014)

Summary In 1999, the IOM issued a cancer quality report that spurred onQOPI development. In 2013, the IOM released a follow-up report. 29 The update reinforces that there is work yet to be accomplished;however,webelievethatoncologyhasmadesigniﬁcantprogresssince1999 and that QOPI has contributed positively. Ongoing evolution oftheQOPIprogram,underthecarefulguidanceofoncologyproviders,is critical to maintaining the relevance and meaningfulness of theprogram to ASCO members and positive impact for their patients. AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST Disclosures provided by the authors are available with this article atwww.jco.org. AUTHOR CONTRIBUTIONSAdministrative support: Kristen McNiff, Terry Gilmore, Pamela J.Kadlubek Manuscriptwriting: All authors Finalapprovalofmanuscript: All authors REFERENCES 1. Hewitt M, Simone J: National Cancer Policy Board, Institute of Medicine:Ensuring Quality Cancer Care. Washington, DC, National Academies Press, 1999 2. MalinJL,SchneiderEC,EpsteinAM,etal:ResultsofTheNationalInitiativefor Cancer Care Quality: How can we improve the quality of cancer care in theUnited States? J Clin Oncol 24:626-634, 2006
Association of Third-Year Medical Students' First Clerkship With Overall Clerkship Performance and Examination Scores
Authors: Susan M Kies, Valerie Roth, Michelle Rowland
Journal: JAMA (2010)

Anecdotal experience has suggested that third-year medical students whose first clerkship is internal medicine may have superior performance throughout the academic year.To determine whether the order of clerkships by specialty is associated with student performance.Clerkship performance records of medical students at all 4 campuses of the University of Illinois College of Medicine who completed their third-year core clerkships from July 2000 through June 2008 (N = 2236) were reviewed.Analysis of covariance was used to test for between-group differences (by first clerkship) in mean National Board of Medical Examiners subject examination scores (range, 0-100), preceptor ratings of clerkship clinical performances (range, 12-30), total overall clerkship grades (range, 12-30), and United States Medical Licensing Examination (USMLE) Step 2 scores, adjusted for sex, campus, and USMLE Step 1 score.First clerkship specialty was significantly associated with mean subject examination scores (family medicine, 71.96 [95% confidence interval {CI}, 70.90-72.98], internal medicine, 73.86 [95% CI, 73.33-74.39], obstetrics/gynecology, 72.36 [95% CI, 71.64-73.04], pediatrics, 73.11 [95% CI, 72.38-73.84], psychiatry, 72.17 [95% CI, 71.52-72.81], surgery, 72.37 [95% CI, 71.73-73.02]; P < .001) and overall clerkship grades (family medicine, 24.20 [95% CI, 23.90-24.90], internal medicine, 25.33 [95% CI, 25.07-25.60], obstetrics/gynecology, 24.68 [95% CI, 24.32-25.05], pediatrics, 24.92 [95% CI, 24.59-25.27], psychiatry, 24.61 [95% CI, 24.33-25.01], surgery 24.97 [95% CI, 24.64-25.30]; P = .01). There was no significant association with preceptor ratings or USMLE Step 2 scores. Pairwise comparisons for mean total overall clerkship grades showed a significant difference for students taking internal medicine first compared with obstetrics/gynecology (mean difference, 0.65; 95% CI, 0.18-1.12), psychiatry (mean difference, 0.66; 95% CI, 0.20-1.12), and family medicine (mean difference, 0.93; 95% CI, 0.37-1.50).Among students at 4 campuses of a US medical school, clerkship order was significantly associated with performance on clerkship subject examinations and overall grades but not with clerkship clinical performance or USMLE Step 2 scores.
Independent sector treatment centres: the first independent evaluation, a Scottish case study
Authors: Allyson M Pollock, Graham Kirkwood
Journal: Journal of the Royal Society of Medicine (2009)

Summary Objectives The £5 billion English Independent Sector Treatment Centre (ISTC) programme remains unevaluated because of a lack of published contract data and poor quality data returns. Scotland has a three-year pilot ISTC, the Scottish Regional Treatment Centre (SRTC), the contract for which is now in the public domain. This study aims to conduct an independent evaluation of the performance of the SRTC during the first year of operation. Design A retrospective analysis of the SRTC comparing activity as reported by hospital episode statistics returned to ISD Scotland with: volume and cost data in the SRTC contract; a 10-month audit carried out by management consultants Price Waterhouse Coopers (PWC); and an internal NHS Tayside performance report. Setting All day-case and inpatient activity at the SRTC from 1 December 2006 to 31 January 2008. Main outcome measures Activity and cost. Results The annual contract was based on patient referrals to the SRTC and not actual treatments. The contract was awarded on the basis of 2624 referrals a year, total value of £5,667,464. According to ISD data, the SRTC performed 831 procedures (32% of annual contract) in the first 13 months worth £1,035,603 (18%). PWC's figures report 2200 referrals (84%) to the SRTC at a cost of 2,642,000 (47%) in the first 10 months. Conclusions Basing the SRTC contract on payments for referrals rather than actual treatment represents a major departure from normal standards of reporting and commissioning and may have resulted in over-payment for referrals for patients who did not receive treatment of up to £3 million in the first 10 months. The PWC report falls well below the standards one would expect of an independent evaluation and we were unable to validate PWC's analysis and the claim of value for money. If wave-one ISTCs in England perform similarly to the SRTC then as much as £927 million may have been paid for patients who did not receive treatment. We recommend a moratorium on all ISTC contracts until the contracts have been published and properly evaluated with respect to work paid for and actual work carried out and quality of care.
The Suppression of <i>Aurora-A/STK15/BTAK</i> Expression Enhances Chemosensitivity to Docetaxel in Human Esophageal Squamous Cell Carcinoma
Authors: Eiji Tanaka, Yosuke Hashimoto, Tetsuo Ito, Kan Kondo, Motoshige Higashiyama, Shigeru Tsunoda, Cristian Ortiz, Yoshiharu Sakai, Johji Inazawa, Yutaka Shimada
Journal: Clinical Cancer Research (2007)

Abstract Purpose: We previously reported that the expression of Aurora-A was frequently up-regulated in human esophageal squamous cell carcinoma (ESCC) tissues as well as cell lines and the up-regulation contributed to a poor prognosis. In this study, we assessed the possibility of Aurora-A suppression as a therapeutic target for ESCC using ESCC cell lines. Experimental Design: We established subclones using vector-based short hairpin RNA (shRNA). Then, we investigated the effect of Aurora-A suppression on proliferation and cell cycle changes in vitro. Next, chemosensitivity against docetaxel was investigated by tetrazolium salt–based proliferation assay (WST assay) and cell number determinations, and furthermore, the type of cell death induced by docetaxel was analyzed by flow cytometry. Finally, to examine the effect of Aurora-A shRNA on proliferation and chemosensitivity against docetaxel in vivo, a s.c. tumor formation assay in nude mice was done. Results: We established two genetically different stable cell lines (510 A and 1440 A) in which levels of Aurora-A were reduced. Cell growth was inhibited by 38.7% in 510 A and by 24.3% in 1440 A in vitro compared with empty vector–transfected controls (510 m and 1440 m), and this growth inhibition was mediated through G2-M arrest as confirmed by flow cytometry. Next, in a WST assay, the IC50 for Aurora-A shRNA-transfected cells was lower than that of empty vector–transfected cells (510 A, 2.7 × 10−7 mol/L; 510 m, 4.8 × 10−7 mol/L; 1440 A, 2.6 × 10−7 mol/L; 1440 m, 4.9 × 10−7 mol/L). In addition, 0.3 nmol/L docetaxel induced a notable level of apoptosis in Aurora-A shRNA-transfected cells compared with empty vector–transfected cells. In the assay of s.c. tumors in nude mice, tumor growth in 510 A was inhibited by 36.1% compared with that in 510 m, and in tumors treated with docetaxel, the suppression of Aurora-A resulted in 44.0% tumor growth suppression in vivo. Conclusions: These results indicated that Aurora-A might play an important role in chemosensitivity to docetaxel, and the suppression of its expression might be a potential therapeutic target for ESCC.
Transformation to Aggressive Lymphoma in Nodular Lymphocyte-Predominant Hodgkin's Lymphoma
Authors: Mubarak Al-Mansour, Joseph M. Connors, Randy D. Gascoyne, Brian Skinnider, Kerry J. Savage
Journal: Journal of Clinical Oncology (2010)

PURPOSE Prior observations suggest a higher risk of transformation of nodular lymphocyte-predominant Hodgkin's lymphoma (NLPHL) to aggressive lymphoma, most commonly diffuse large B-cell lymphoma (DLBCL), than in classical Hodgkin's lymphoma. We evaluated the frequency of transformation in all patients diagnosed with NLPHL at the British Columbia Cancer Agency with long-term follow-up. PATIENTS AND METHODS The Lymphoid Cancer Database of the British Columbia Cancer Agency was searched to identify all patients diagnosed with NLPHL between 1965 and 2006. After pathologic review, 95 patients with NLPHL were confirmed. Results Patients with NLPHL had the following characteristics at diagnosis: median age of 37 years, 73% male, and 68% stage I or II disease. With a median follow-up time for living patients of 6.5 years (range, 2.5 to 33 years), 13 patients (14%) experienced transformation to aggressive lymphoma (median time to transformation, 8.1 years; range, 0.35 to 20.3 years). The actuarial risk of transformation to aggressive lymphoma was 7% and 30% at 10 and 20 years, respectively. Transformation was more likely in patients with initial splenic involvement (P = .006) at the time of diagnosis of NLPHL. The 10-year progression-free and overall survival rates in patients with transformed lymphoma were 52% and 62%, respectively. CONCLUSION The risk of transformation in patients with NLPHL to DLBCL is substantial and underappreciated. Because transformation can occur years after the primary diagnosis of NLPHL, long-term follow-up of these individuals is necessary to accurately estimate the risk of development of secondary DLBCL.
Molecular Pathways: Hippo Signaling, a Critical Tumor Suppressor
Authors: Ana Sebio, Heinz-Josef Lenz
Journal: Clinical Cancer Research (2015)

The Salvador-Warts-Hippo pathway controls cell fate and tissue growth. The main function of the Hippo pathway is to prevent YAP and TAZ translocation to the nucleus where they induce the transcription of genes involved in cell proliferation, survival, and stem cell maintenance. Hippo signaling is, thus, a complex tumor suppressor, and its deregulation is a key feature in many cancers. Recent mounting evidence suggests that the overexpression of Hippo components can be useful prognostic biomarkers. Moreover, Hippo signaling appears to be intimately linked to some of the most important signaling pathways involved in cancer development and progression. A better understanding of the Hippo pathway is thus essential to untangle tumor biology and to develop novel anticancer therapies. Here, we comment on the progress made in understanding Hippo signaling and its connections, and also on how new drugs modulating this pathway, such as Verteporfin and C19, are highly promising cancer therapeutics.