tbuckley/cabot-search huggingface dataset:
Targeting the extrinsic apoptotic pathway in endometrial carcinoma cell lines and tumor cell explants
Authors: X. Matias-guiu, X. Dolcet, D. Llobet, A. Poveda, J. Pallares, N. Eritia, A. Yeramian, A. Sorolla, E. Ortega, A. Llombart-Cussac
Journal: Journal of Clinical Oncology (2009)

e16555 Background: Endometrial carcinoma (EC) frequently shows deregulation of the extrinsic apoptotic pathway. One of the critical regulators of apoptosis resistance in EC is FLIP, under the control of NFkB and a cellular complex composed of CK2, KSR1, and BRAF. Methods: Four different EC cell lines, which are known to exhibit resistance to TRAIL/FAS-induced apoptosis (Ishikawa, KLE, HEC1A, and RL-95) were exposed to various pharmacologic substances that target proteins involved in the regulation of the extrinsic apoptotic pathway and receptor tyrosine kinases including bortezomib, sorafenib, sunitinib, DRB, apigenin, MG-132, epoxomicin, and ALLN. Moreover, EC cell lines were subjected to down-regulation of several of these genes (FLIP, CK2, KSR1, and BRAF) by shRNA. Cell viability and apoptotic morphology was determined. Results were validated in tumor cell explants. Results: Bortezomib induced cell death on EC cells and primary explants to a 70% extent. However, 100% of treated explants and cell lines activated NF-kB instead of blocking its transcriptional potential. Combination of sunitinib plus bortezomib induced 75% fold reduction in NFkB activity and induced a 5% of synergistic increse of apoptotic cell death in Ishikawa cells. Treatment of the four cell lines with TRAIL failed to induce cell death. However, FLIP knock-down sensitized the cells to TRAIL-induced apoptosis (80%). Moreover, down-regulation of CK2, KSR1, and BRAF by pharmacological inhibition, or shRNA, reduced FLIP cellular levels, and induced TRAIL-dependent apoptosis in 70%-100% of EC cell lines tested. Sorafenib induced a dose-dependent cell death in all four cell lines, to a 70%-100% extent at 48 hours. Conclusions: In vitro pharmacologic targeting of the apoptotic pathway effectively induces cell death in EC cell lines. These findings justify clinical trials with these agents in EC. [Table: see text]
Breast cancer care in Latin America and the Caribbean (LAC)
Authors: E. L. Cazap, A. Buzaid, R. Chacon, C. Garbino, J. de la Garza, A. Guercovich, E. Mickiewicz, F. Orlandi, G. Schwartsmann, C. Vallejos
Journal: Journal of Clinical Oncology (2007)

21140 Background: This study was designed to evaluate breast cancer care (BCC) in LAC trough a survey of 65 questions. Methods: We surveyed 96 opinion leaders (OL) from 12 countries that were first contacted by a researcher explaining the project and methodology. A phone interview was done by a specialist in epidemiology surveys. Answers were analyzed by center or country with Intercooled State 8 software (State Corp.) Results: 92 % OL confirm that there is no country law or guidelines making mandatory mammographyc screening. Nearly 75% of the OL stated that some type of cancer registry was available. The first consultation is done by gynecologists or breast cancer surgeons (83%), clinicians (13%) and surgeons (4%).Time lapsed from consultation until pathologic diagnosis was less than 3 months in 62% (country) and 91% (centers). Accessibility for hormone receptor and molecular markers is very good in specialized centers: 90% and 83% respectively but it is only available to 52% and 5% of country patients. Conservative surgery is widely accepted (87%) and 71% OL are able to perform sentinel node biopsies (centers). Systemic treatment is mainly based in Anthracyclines and Tamoxifen. The treatment coverage at centers is through medical insurance companies (53%), government (28%) and patient (19%) while 67% of country patients are government covered. Radiation treatment is mainly indicated by oncologists and 62% consider that radiotherapy centers in their countries are insufficient. There is adequate availability of morphine for 93% (centers) and 82% (countries).The choice of the chemotherapy or hormonal adjuvant treatment is free for 74% of those surveyed at their centers and in 23% is pre-established by the coverage. Majority of opinions are that all types of research are deficient. It is mainly organized in public institutions and sponsored by pharmaceutical companies (76%). Full results will be presented. Conclusions: We obtained data about the reality of BCC in the region. There is a general lack of prevention plans. Time to diagnosis and first treatment is similar to developed countries. Treatment according to stage is similar to international standards. Radiotherapy availability is poor. Based on this data a strategic plan for BCC in LAC will be developed. Supported by a grant from The Breast Cancer Research Foundation No significant financial relationships to disclose.
Randomized phase III trial comparing vincristine, actinomycin, cyclophosphamide (VAC) with VAC/V topotecan/cyclophosphamide (TC) for intermediate risk rhabdomyosarcoma (IRRMS). D9803, COG study
Authors: C. A. Arndt, D. S. Hawkins, J. A. Stoner, M. D. Wharam, D. A. Rodeberg, D. M. Parham, W. H. Meyer
Journal: Journal of Clinical Oncology (2007)

9509 Background: IRRMS was defined as nonmetastatic alveolar (A) RMS or undifferentiated sarcoma (UDS); stage (stg) 2 and 3, group (gr) III embryonal (E) RMS; stg 4 ERMS &lt;10y. IRRMS had a 5 yr failure free survival (FFS) of 64% on IRS IV. Since T alone and with C has significant activity in RMS, we tested whether alternating VAC/VTC improved FFS for IRRMS compared with VAC alone. Methods: Patients (pts) &lt; 50 y with IRRMS with adequate organ function were randomized to 39 wks of VAC (V=1.5 mg/m 2 , A=0.045 mg/kg, C=2.2 g/m 2 q 3 wk) vs VAC alternating with VTC (T=0.75 mg/m 2 /d ×5, C=250 mg/m 2 /d ×5 q 3 wk), with additional wkly V; doses adjusted for age &lt;3y; local therapy was after wk 12. Pts with parameningeal RMS/meningeal extension (PME) were nonrandomly treated with VAC and immediate XRT. Primary study endpoint was FFS. The study was designed with 80% power (5% 2-sided alpha level) to detect an increase in 5 yr FFS from 64% to 75%, a relative risk (RR) of 0.64, with VAC/VTC, requiring 518 randomized pts. Results reflect the 3 rd of 4 planned analyses (75% information); O'Brien Fleming adjusted alpha level is 0.0166; and Cox PH model was used. Results: 620 eligible pts were entered from 9/99 to 8/05: 266 randomized to VAC, 253 to VAC/VTC, 101 PME patients were nonrandomly treated with VAC. Treatment strata were ERMS stg 2/3, gr III 37%; ERMS grp IV &lt;10 y 6%; ARMS/UDS stg 1 or gr I 16%; ARMS/UDS other 25%; PME 16%. 3% of pts were &lt;1 y, 69% 1–9 y, 28% ≥10 y; 13% of pts were stg 1; 26% stg 2; 54% stg 3; 7% stg 4. 77% pts had gr III tumors. Primary tumor sites were PM in 35% pts, extremity 15%, bladder/prostate 16%, retroperitoneal/perineal 15%, other 19%. Median follow up is 2.4 yrs. FFS at 2 yrs is 77% with VAC and 72% with VAC/VTC. Observed data are inconsistent with hypothesized improvement under VAC/VTC (RR=1.20, 98.34% CI: 0.78–1.85, p=0.3). Similar patients on IRS IV had 2 yr FFS of 77%. 2 yr survival (OS) with VAC: 91%; VAC/VTC: 87% (RR=0.94, CI: 0.55–1.59, p=0.8). There were 12 2 nd malignancies and 10 deaths as first events. 4 of 10 deaths were from hepatopathy, which decreased in incidence following dose changes for A and C. Conclusions: In IRRMS, VAC/VTC does not significantly improve FFS nor OS versus VAC, and outcome is similar to IRS IV. No significant financial relationships to disclose.
Next Generation Sequencing. a Key in Search of Locks?
Authors: A. Ferreira, A.S.D.A. Gomes, P.M. Hoff, F.P. Costa, D.F. Saragiotto, A. Katz, G.D.S. Fernandes, K.K. Machado, F.C. Azevedo, M.I.F.M. Braghiroli, R. Coudry, S.I. Meireles
Journal: Annals of Oncology (2014)
Tumor <i>PIK3CA</i> genotype and prognosis: A pooled analysis of 4,241 patients (pts) with early-stage breast cancer (BC).
Authors: Dimitrios Zardavas, Luc Te Marvelde, Roger Milne, Heikki Joensuu, Mary Ellen Moynahan, Bryan Hennessy, Ivan Bieche, Lao H Saal, Olle Stal, Barry Iacopetta, Jeanette Dupont Jensen, Sandra O'Toole, Mattia Barbareschi, Shinzaburo Noguchi, Enrique Lerma, Qing Wang, Martine J. Piccart-Gebhart, Christos Sotiriou, Stefan Michiels, Sherene Loi
Journal: Journal of Clinical Oncology (2015)

516 Background: PIK3CA mutations (mt) are frequently observed in BC but their clinical relevance is unclear. We performed an individual pt data pooled-analysis to evaluate the prognostic impact of PIK3CA status on early-stage BC. Methods: Participating studies were identified by literature search. Associations of PIK3CA status with clinicopathologic characteristics were tested. Cox regression models were applied adjusting for age, tumor size, nodes, grade, ER and HER2 status, treatment and study. Invasive disease-free survival (IDFS) was the primary endpoint, followed by distant disease-free survival (DDFS), overall and by BC subtypes. Results: Data from 16 studies were included. Median age was 56yrs (18-96) and median follow-up was 6.5yrs; 1384 pts (33%) received chemotherapy, 1147 (27%) endocrine monotherapy, 816 (19%) both and 894 (21%) none/unknown. PIK3CA mt occurred in 26.9%: 55.2% exon 20 and 36.2% exon 9. They were associated with ER+ tumors, increasing age, lower grade (all p < 0.001) and smaller size (p = 0.04). Incidence of PIK3CA mt was 15%, 23%, 32% in the ER-/HER2-, HER2+ and ER+/HER2- subtypes respectively (p < 0.001). In the univariate analysis, PIK3CA mt were associated with better IDFS: HR = 0.85 [95%CI:0.75-0.96]; p = 0.0009. A statistically significant non-proportional prognostic effect was observed (p = 0.02): during the first 3 yrs PIK3CA mt had better IDFS (HR = 0.73 [0.60-0.88]) compared to after 3yrs (IDFS HR = 0.96[0.8-1.1]; P interaction:0.03). There was no significant interaction by BC subtype (p = 0.6) and no significant differences by exon 9 or 20 site (p = 0.7). In the multivariate analysis, PIK3CA status did not remain statistically significant overall (HR = 0.94 [0.8-1.2]; p = 0.6) nor in the first 3 yrs. Results were similar for the DDFS endpoint. In further analyses, a significant interaction between PIK3CA status and age was found, remaining after adjustment (P = 0.04). PIK3CA mutant BCs had significantly better IDFS in women ≤ 50yrs (HR = 0.65 [0.4-0.95]) but not > 50yrs (HR = 1.10 [0.9-1.4]; Pint = 0.01). Conclusions: PIK3CA mutations are associated with a better prognosis. This effect is greatest in young women for whom PIK3CA status could potentially refine treatment decisions.
Uterine Sarcoma, Version 1.2016
Authors: Wui-Jin Koh, Benjamin E. Greer, Nadeem R. Abu-Rustum, Sachin M. Apte, Susana M. Campos, Kathleen R. Cho, Christina Chu, David Cohn, Marta Ann Crispens, Don S. Dizon, Oliver Dorigo, Patricia J. Eifel, Christine M. Fisher, Peter Frederick, David K. Gaffney, Suzanne George, Ernest Han, Susan Higgins, Warner K. Huh, John R. Lurain, Andrea Mariani, David Mutch, Amanda Nickles Fader, Steven W. Remmenga, R. Kevin Reynolds, Todd Tillmanns, Fidel A. Valea, Catheryn M. Yashar, Nicole R. McMillian, Jillian L. Scavone
Journal: Journal of the National Comprehensive Cancer Network (2015)

The NCCN Guidelines for Uterine Neoplasms provide interdisciplinary recommendations for treating endometrial carcinoma and uterine sarcomas. These NCCN Guidelines Insights summarize the NCCN Uterine Neoplasms Panel's 2016 discussions and major guideline updates for treating uterine sarcomas. During this most recent update, the panel updated the mesenchymal tumor classification to correspond with recent updates to the WHO tumor classification system. Additionally, the panel revised its systemic therapy recommendations to reflect new data and collective clinical experience. These NCCN Guidelines Insights elaborate on the rationale behind these recent changes.
Tumor characteristics in obese women with breast cancer.
Authors: Jennifer Chun, Ana Paula Refinetti, Freya Ruth Schnabel, Alison Price, Jessica Billig, Arielle Cimeno, Shira Schwartz, Amber Guth, Deborah M. Axelrod
Journal: Journal of Clinical Oncology (2012)

179 Background: Obesity is an established risk factor for postmenopausal breast cancer. Though women with high BMI tend to develop less aggressive molecular subtypes, previous studies have shown that they still have a higher risk of recurrence and worse prognosis. The biological mechanisms for this difference in outcome have yet to be identified. The purpose of this study is to determine the correlation between obesity and tumor characteristics, including Ki67, and Oncotype DX scores in both pre- and post-menopausal women. Methods: The Breast Cancer Database of NYU Langone Medical Center was queried for patients who were newly diagnosed with invasive breast cancer. We looked at the following variables: menopausal status, body mass index (BMI), histology, stage, ER/PR/Her2-neu status, Ki67, and Oncotype DX scores. Obesity was defined as having a BMI (kg/m 2 ) ≥30. We looked at Ki67 as a continuous variable. Oncotype scores were categorized as low (&lt;18), intermediate (18-30), and high (&gt;31). Statistical analyses were performed using Spearman Correlation Coefficients. Results: Out of a total of 648 patients with a median age of 59 years, 153 (24%) women had a BMI≥30. The majority of the obese women had stage I and II (88%) cancers that were ER positive (84%), PR positive (74%), Her2-neu negative (86%), with mean Ki67 of 22%, and low to intermediate Oncotype DX scores (85%). However, when compared with women of BMI &lt;30, there was no correlation between BMI and tumor characteristics, even when stratified by menopausal status. Conclusions: In our cohort, obesity was not correlated with tumor stage, histology, Ki67 and Oncotype DX scores, even after adjusting for menopausal status. There are other factors that may explain the higher risk of recurrence and worse prognosis of breast cancer in obese women, such as insulin resistance, and obesity-related inflammatory cytokines that are independent of breast cancer subtypes and genomics. Treatment-related factors, such as non-compliance and inadequate dosing of chemotherapeutic agents, may also play a role in the worse outcome seen in this population. Further studies are necessary to identify measurable molecular characteristics of breast cancer in obese women that would allow us to predict more aggressive disease.
Establishment of a Hairy Cell Leukemia Cell Line Carrying Tac Antigen and Phagocytic Activity With B-Cell Characteristics&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Y Matsuo, K Sagawa, M Morita, J Minowada, M M Yokoyama
Journal: JNCI Journal of the National Cancer Institute (1986)

A hairy cell leukemia cell line designated "Hair-M" was established in a suspension culture derived from the peripheral blood of an 86-year-old Japanese male with a diagnosis of hairy cell leukemia. The Hair-M cells were identified as having prominent hair-like cytoplasmic projections by examination with phase-contrast and scanning electron microscopy. These cells displayed ruffled membranes and stublike microvilli similar to those observed on the surfaces of cells in the peripheral blood of the patient. Immunologic and cytochemical studies on the Hair-M cells confirmed derivation from the clone of the patient's leukemia cells. Although the cultured Hair-M cells had definite B-cell characteristics, such as IgG kappa-chains on the surface and in cytoplasm, they also demonstrated Tac antigen, which is usually expressed on activated T-cells, and myelomonocyte antigens determined by OKM-1 and MCS-1 monoclonal antibodies. Other cell surface markers, including E(-), IgGFc(-), IgMFc(-), C3R(+), Ia-like antigen(+), OKT9(+), OKT10(+), and terminal deoxynucleotidyl transferase(-), were detected; no Epstein-Barr virus-determined nuclear antigen was detected. The karyotype of the Hair-M cells was determined to be 46XY with -11, -14, and two marker chromosomes. The Hair-M cells also had phagocytic activity to rabbit anti-human IgG serum-coated polyacrylamide gel particles.
Investing in Better Care for Patients Dying in Nursing Homes
Authors: Mary Beth Hamel
Journal: New England Journal of Medicine (2015)

Dame Cicely Saunders founded St. Christopher’s Hospice in London in the 1960s and established the principles of modern hospice care. Remarkably, she was trained as a nurse, social worker, and physician — the professions instrumental in the delivery of high-quality care at the end of life. In 1982, the U.S. Congress expanded Medicare to include coverage for hospice care. Patients with a life expectancy of 6 months or shorter who are willing to forgo curative treatments may choose the Medicare hospice benefit. The per diem payment covers the costs of care by the hospice team (which typically includes nurses, physicians, . . .
Chromosome Studies of a Contagious Reticulum Cell Sarcoma of the Syrian Hamster
Authors: Cooper, Herbert L., Mackay, Carol M., Banfield, William G.
Journal: JNCI Journal of the National Cancer Institute (1964)

Journal Article Chromosome Studies of a Contagious Reticulum Cell Sarcoma of the Syrian Hamster Get access Herbert L. Cooper, Herbert L. Cooper National Institute of Dental Research and National Cancer Institute,4Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar Carol M. Mackay, Carol M. Mackay National Institute of Dental Research and National Cancer Institute,4Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar William G. Banfield William G. Banfield National Institute of Dental Research and National Cancer Institute,4Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 33, Issue 4, October 1964, Pages 691–706, https://doi.org/10.1093/jnci/33.4.691 Published: 01 October 1964 Article history Received: 16 April 1964 Published: 01 October 1964
Inflammation activation and resolution in human tendon disease
Authors: Stephanie G. Dakin, Fernando O. Martinez, Clarence Yapp, Graham Wells, Udo Oppermann, Benjamin J. F. Dean, Richard D. J. Smith, Kim Wheway, Bridget Watkins, Lucy Roche, Andrew J. Carr
Journal: Science Translational Medicine (2015)

Improved understanding of the role of inflammation in tendon disease is required to facilitate therapeutic target discovery. We studied supraspinatus tendons from patients experiencing pain before and after surgical subacromial decompression treatment. Tendons were classified as having early, intermediate, or advanced disease, and inflammation was characterized through activation of pathways mediated by interferon (IFN), nuclear factor κB (NF-κB), glucocorticoid receptor, and signal transducer and activator of transcription 6 (STAT-6). Inflammation signatures revealed expression of genes and proteins induced by IFN and NF-κB in early-stage disease and genes and proteins induced by STAT-6 and glucocorticoid receptor activation in advanced-stage disease. The proresolving proteins FPR2/ALX and ChemR23 were increased in early-stage disease compared to intermediate- to advanced-stage disease. Patients who were pain-free after treatment had tendons with increased expression of CD206 and ALOX15 mRNA compared to tendons from patients who continued to experience pain after treatment, suggesting that these genes and their pathways may moderate tendon pain. Stromal cells from diseased tendons cultured in vitro showed increased expression of NF-κB and IFN target genes after treatment with lipopolysaccharide or IFNγ compared to stromal cells derived from healthy tendons. We identified 15-epi lipoxin A4, a stable lipoxin isoform derived from aspirin treatment, as potentially beneficial in the resolution of tendon inflammation.
Continuity in general practice
Authors: G. Taylor
Journal: BMJ (2001)

EDITOR—With reference to the article by Guthrie and Wyke,1 continuity in general practice is one of those obvious good things, but it is too complicated to be something with an easy answer, an all or nothing. In 1988 I wrote a personal view which proposed that patients might see a different doctor for acute illness than for their long term problems.2 They might even travel to see this personal doctor. This was met with some amazement by some of my colleagues.

The changes in a society that now expects to be able to get money at midnight and shop in Tesco at 2 am (and I am as guilty as anyone else) means that, in places where general practice demand is high, systems have to be developed to cope. So we have walk in centres, triage systems, or duty doctors seeing all those strange things, social, medical, or just “I'm off work today,” that need to be seen now. In quiet places of low demand, …
EFFICACY, SAFETY AND IMPACT ON QUALITY OF LIFE OF A TREATMENT WITH SORAFENIB IN ELDERLY CANCER PATIENTS WITH ADVANCED HEPATOCELLULAR CARCINOMA. RESULTS OF A PHASE II STUDY
Authors: E Massa, C Spiga, L Chessa, T Zolfino, R Piras, C Madeddu, S Lepori, G Serra, S Marini, G Mantovani
Journal: Annals of Oncology (2009)
Oncogenic HPV-DNA testing alone as cervical cancer screening in high-risk population of Southern Mexico
Authors: F. Gutierrez-Delgado, J. E. Enriquez-Freire, H. Leon-Velasco, J. A. Manzur-Perez, A. Baron-Rojas, J. Perez-Romero, J. Vazquez-Luna, S. Terrazas-Espitia, J. Cortes-Guzman, S. Marcial-Toledo
Journal: Journal of Clinical Oncology (2008)

16519 Background: A causal relationship has been established between oncogenic HPV infection and cervical cancer. Clinical trials have showed that HPV-DNA testing is considerably more sensitive than cytology. Southern Mexico is a region with the highest incidence of cervical cancer in the country. In this study we evaluate the feasibility of oncogenic HPV-DNA testing alone as a potential cervical cancer screening program in a high-risk region. Methods: Between 08/2006 and 12/2007, HPV-DNA testing was offered to women aged 14 to 89 years. Testing for the DNA of oncogenic HPV types (16,18,31,33, 35, 39, 45, 51, 52, 56, 58, 59 and 68) was performed on endocervical samples obtained with the Cytobrush method, using the Hybrid Capture II (hC2) assay (Digene Corp, Gaithersburg, MD, USA). The results of the HPV test were expressed as relative lights units (RLU). An RLU ≥ 1.0 was considered to be positive. Those women who had a HPV-DNA positive test were referred for colposcopy, and if indicated, directed cervical biopsy. Results: 309 women (median age 34 years, range: 16- 87) were recruited. 212 (69%) of them were ≥ 30 years old. Overall, 67 (22%) women had a positive viral load (median 56.74 RLU; range: 1.04 - 9019). Among 97 women younger than 30 years old, HPV-DNA testing was positive in 29 (30%) (median: 70.45 RLU; range: 1.11 - 2403.62) and in 38 (18%) out of 212 women ≥ 30 years old: median 23.72 (1.04 - 9019). Thirty-five (52%) out of 67 women who had a HPV positive test were evaluated by colposcopy and the histopathological diagnosis of HPV/HSIL was established in 25 (71%) women (<30 years old n= 17; ≥ 30 years old n=8). Conclusions: Oncogenic HPV-DNA testing alone is a feasible cervical cancer screening program in a high-risk population. HPV-DNA testing increases the number of women need to be identified and treated earlier. No significant financial relationships to disclose.