tbuckley/cabot-search huggingface dataset:
Methylseleninic acid to enhance the efficacy of doxorubicin and paclitaxel in triple-negative breast cancer cells.
Authors: Meijun Long, Yong Huang, Jun An, Hang Su, Renbin Liu
Journal: Journal of Clinical Oncology (2016)

e12563 Background: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer without the expression of hormone receptor or HER2. Due to the “triple-negative” feature, chemotherapy is the only systemic treatment available, and the first line regimen is anthracycline and taxane-based chemotherapy. Although TNBC generally has a favorable initial response to chemotherapy, its prognosis is greatly compromised by acquired drug resistance and undesirable side effects. Therefore, new agents are urgently needed to overcome the resistance and enhance the chemosensitivity. Methylseleninic acid (MSA) is a second-generation organic selenium compound. It has been demonstrated as a potent cancer cell killing drug in vitro and in vivo. In combination therapy, MSA has shown to enhance the therapeutic efficacy of several chemodrugs in vitro. However, the effect of MSA on doxorubicin (DOX) and paclitaxel (PA) in TNBC cells are still under exploring. Methods: Three TNBC cell lines, MDA-MB-231, MDA-MB-436 and MDA-MB-468, were tested in this study. Cellular viability was determined by the MTT assay and cell morphology was recorded under a light microscope. Cellular apoptosis was detected using Annexin V/PI staining assay and cell cycle distribution was analyzed by flow cytometry. Protein levels were examined by Western blotting. Results: PA treatment alone activated G2/M checkpoint as evidenced by G2/M phase cell cycle arrest, apoptosis induction, increased phosphorylation of p53 and PARP1 cleaveage, as well as decreased accumulation of G2/M cell cycle proteins. Combination treatment of MSA and PA further enhanced this effect. DOX treatment alone also activated p53 and induced apoptosis, and the adding of MSA further increased the level of phospho-p53 and apoptosis rate. Conclusions: We found that MSA synergistically enhanced the growth-inhibitory effect of doxorubicin and paclitaxel in TNBC cells. The synergism was partialy due to the induction of caspase-mediated apoptosis, arrest of cell cycle progression at the G2/M in the combinatory effect of MSA and PA. Our findings indicated that combination therapy with MSA and either DOX or PA is a potential therapeutic strategy for TNBC.
Clinical experience with infliximab biosimilar in psoriasis
Authors: F. Ricceri, L. Pescitelli, L. Lazzeri, F. Prignano
Journal: British Journal of Dermatology (2017)

biosimilar medicines are biological medicine that have been developed to be highly similar and clinically equivalent to an existing biological medicine. Just as patent expiry for conventional drugs has led to the marketing of generic versions, the expiry of data protection and patents for original biologics has prompted development of biosimilars.

This article is protected by copyright. All rights reserved.
Homosexuality and the military
Authors: F D Jones, R J Koshes
Journal: American Journal of Psychiatry (1995)

Homosexuality has remained a focus of military concern despite society's increasing acceptance of homosexual men and women and evidence that homosexuals have served and currently serve in the U.S. armed forces. President Clinton has stated a determination to end discrimination against homosexuals in the military and reverse the exclusionary policy on homosexuals serving in the armed forces. The authors review the history of the policy of the U.S. military to exclude homosexuals from serving in the armed forces.The data for this study were drawn from military archives and court cases that have shaped U.S. policy excluding homosexuals from serving in the armed forces. The three main arguments are addressed: 1) homosexuality is a mental disorder rendering a person unstable, 2) homosexual service members are a source of poor morale for military units, and 3) homosexual service members are poor security risks.Considerable evidence demonstrates that homosexuals in the military pose no documented threat to national security and show no evidence of poor work performance.Although issues of morale and fraternization in the military remain challenges, no evidence in this review supports the exclusion of homosexuals from service in the U.S. armed forces.
Identifying patients according to breast cancer stage and ER/HER2 receptor status using claims data.
Authors: Cynthia De Luise, Daniel C Beachler, Ruihua Yin, Jamileh Jemison, Philip T Cochetti, Kelsey Gangemi, Stephan Lanes
Journal: Journal of Clinical Oncology (2017)

e13096 Background: Safety analyses of targeted oncology therapies often require cancer stage and receptor status. Automated claims databases offer the largest populations to study rare outcomes, but lack these characteristics. We conducted a validation study of claims data using predictive models to identify two cohorts of women with early-stage and advanced-stage ER+/HER2- breast cancer (ESBC and ASBC, respectively). Methods: Retrospective cohort and validation study using electronic data linkage of a nationwide claims database (HealthCore Integrated Research Database – HIRD) and Anthem’s Cancer Care Quality program (CCQP). The CCQP served as a validation sample. We used claims data to develop two predictive models to estimate breast cancer stage and receptor status. We applied these models to the HIRD to identify ER+/HER2- ESBC and ASBC cohorts. In each cohort we assessed adverse event (AE) rates. Results:: In addition to breast cancer diagnoses, predictive models for ER+/HER2- ESBC and ASBC included 21 and 15 factors, respectively (Table).When compared to an a priori ASBC algorithm developed from clinical experience, the claims-based predictive model for ASBC had better PPV (0.78 v. 0.62) with similar sensitivity (0.39 v. 0.38). For the ASBC cohort, selected AE rates per 100 person-years included: anemia, 26.4; neutropenia, 14.3; pulmonary embolism, 5.7; and leukopenia, 4.0. Conclusions: Identification ofcancer stage and biomarkers using claims data can be improved through predictive modeling. ER+/HER2- ESBC and ASBC cohorts are being utilized for characterizing indications and conducting safety evaluations of targeted therapies. [Table: see text]
Place de l'échoendoscopie dans la prise en charge du cancer rectal en France
Authors: AM Bouvier, G Launoy, P Grosclaude, A Buémi, B Trétarre, M Velten, F Ménégoz, AV Guizard, J Peng, F Molinié, A Danzon, J Faivre
Journal: Endoscopy (2006)

L'apport de l'échoendoscopie dans le cancer du rectum est indispensable pour savoir s'il y a une indication de radiothérapie préopératoire.La mise en commun des données des registres des cancers français, au sein du réseau FRANCIM, a permis de connaître la place qu'occupait l'échoendoscopie dans le bilan d'extension du cancer du rectum dans la population française.
Evaluation des prothèses métalliques expansives couvertes pour le traitement des sténoses oesophagiennes bénignes: résultats d'une étude multicentrique de la Société Française d'Endoscopie Digestive
Authors: A Chryssostalis, PN d'Halluin, D Heresbach, M Gaudric, P Bichard, G Vanbiervliet, F Fumex, D Coumaros, H Lamouliatte, F Prat
Journal: Endoscopy (2009)

But: Evaluer la faisabilité de la mise en place et de l'ablation endoscopique de prothèses métalliques couvertes dans les sténoses bénignes de l'œsophage après une période de calibrage.
Posterior individual predictive cancer incidences in clinical genetic models.
Authors: Tinhinan Belaribi, Gregory Nuel
Journal: Journal of Clinical Oncology (2016)

e13029 Background: In clinical genetic oncology, cancer risk assessment is of primary importance to establish the decision thresholds needed by clinicians to define prevention strategies. Several models are used in cancer centers to evaluate patient risks. For example at Institut Curie, we use a survival breast cancer model with genetic factor X (BRCA1, BRCA2) and familial frailty Z (e.g. unobserved polygenic factor). It allows to predict the lifelong risk for an unaffected woman to be diagnosed with breast cancer given her family history FH. For that purpose, it is necessary to calculate the individual cancer incidences, also called individual hazard rates. Methods: In this work, we present three methods to evaluate the individual hazard rates for breast and ovarian cancers, using the distribution a posteriori of X and Z knowing FH. In the first method called « MAP » (maximum a posteriori) we simply use the couple (XMAP,YMAP) that maximize individual posterior distribution. In the second method called « average », instead of considering only one value of (X, Z) we integrate over the whole posterior distribution. Finally, we present the « exact » method which is similar to « average » at the noticeable difference that integration is performed over P(X, Z | FH, T > t); the updated individual posterior distribution taking into account the age of the patient in the years to come. Results: We show that the hazard rates are underestimated with MAP because of the skewed relative hazard of the frailty, and overestimated with the average method. Both methods are easy to compute but both give biased results since they don't consider patients evolution over time. Indeed, the passing time without being affected alters the posterior distribution of (X, Z) and hence usually subsequently reduces the cancer risks. Our method presented here is technically more sophisticated but provide unbiased results. Conclusions: In the context of genetic models for predictive cancer risks based on FH, we presented a new exact method to calculate unbiased individual posterior incidences taking into account patient aging in the forthcoming years after genetic counseling. The new method could easily replace the simpler biased approaches which are usually used with these models.
TIBIOFEMORAL LATERAL COMPARTMENT'S MORPHOLOGY AS A RISK FACTOR: A RADIOGRAPHIC COMPARISON BETWEEN ACL-RUPTURED AND NON-INJURED SUBJECTS
Authors: Renato Andrade, Sebastiano Vasta, Rogério Pereira, Ana Leal, Luís Silva, Cátia Saavedra, Ricardo Bastos, Rui Rocha, Alberto Monteiro, Nuno Sevivas, Rocco Papalia, João Espregueira-Mendes
Journal: British Journal of Sports Medicine (2017)

Background Tibiofemoral bone morphology has been proposed as a potential risk factor for anterior cruciate ligament (ACL) rupture, with recent increasing interest in the lateral femoral condyle. Objective Investigate several tibiofemoral bone morphology measurements as risk factors for rupturing the ACL. Design Retrospective case–control study. Setting Clinical setting. Patients (or Participants) 200 ACL-ruptured patients and 200 normal subjects without history of previous knee injuries, with a mean age of 24 years old. Main Outcome Measurements Presence or not of ACL rupture. Assessment of Risk Factors Radiographic measurements of the distal epiphysis/diaphysis of the femur and proximal epiphysis of the tibia were performed, including: anteroposterior-flattened surface of the femur's lateral condyle; femur's diaphysis anteroposterior distance; anteroposterior distance of the femur's lateral condyle; height of the femur's lateral condyle; anteroposterior distance of the tibial plateaus; tibial slope. In addition, three morphological ratios were calculated. Results Most of the bone morphological parameters were different between genders (P&lt;0.001). Similarly, there were significant differences between ACL-ruptured and control subjects (P&lt;0.001), either for total sample or subgrouped by gender. Logistic regression model showed that 5 bone morphological parameters were significantly associated with ACL rupture (AUC=0.967, P&lt;0.001). The calculated ratios showed significant accuracy in identifying individuals with higher risk of sustaining an ACL injury (P&lt;0.001). Conclusions Several tibiofemoral bone morphology radiographic measurements are associated with an ACL rupture. Morphological ratios based on these measurements seem to identify individuals at higher risk of sustaining an ACL rupture. These findings might contribute to health counselling on level of sports participation. Moreover, it may help to identify individuals who may benefit the most from secondary prevention programs, where the risk of new injury is very high.
Screening for Testicular Cancer: U.S. Preventive Services Task Force Reaffirmation Recommendation Statement
Journal: Annals of Internal Medicine (2011)

Description: Reaffirmation of the 2004 U.S. Preventive Services Task Force (USPSTF) recommendation statement on screening for testicular cancer. Methods: The USPSTF performed a targeted literature search for benefits and harms of screening for testicular cancer in asymptomatic males and found no new studies. Recommendation: The USPSTF does not recommend screening for testicular cancer in asymptomatic adolescent or adult males. (Grade D recommendation)
Pruritus in patients treated with targeted cancer therapies: Systematic review and meta-analysis.
Authors: Courtney J. Ensslin, Alyx C. Rosen, Shenhong Wu, Mario E. Lacouture
Journal: Journal of Clinical Oncology (2013)

e13571 Background: Pruritus is a disabling symptom that has been anecdotally described in patients treated with targeted cancer therapies, and reports on its incidence vary. The overall risk to develop pruritus in these patients has not been systematically ascertained. We conducted a systematic review and meta-analysis of the literature to determine the incidence and risk of developing pruritus among patients treated with targeted therapies. Methods: Databases from PubMed and Web of Science from January 1998 until July 2012 and abstracts presented at the American Society of Clinical Oncology annual meetings from 2004 through 2012 were searched to identify relevant studies. The incidence and relative risk (RR) of pruritus were calculated using random-effects or fixed-effects model depending on the heterogeneity of included studies. Results: Of 5,065 studies initially identified, a total of 20,532 patients from 144 studies were included for analysis. The summary incidences of all-grade and high-grade pruritus were 17.4% (95% confidence interval (CI): 16.0%-19.0%) and 1.4% (95% CI: 1.2%-1.6%). From randomized controlled trials, patients treated with targeted therapies had a significantly increased risk of developing all-grade pruritus, with an overall RR of 2.59 (95% CI: 2.03-3.30, p&lt;0.001); there was a significant variation among different classes of drugs (P&lt;0.001). Conclusions: There is a significant risk of developing pruritus in cancer patients receiving targeted therapies. In order to prevent suboptimal dosing and reductions in quality of life, these patients should be counseled and treated against this disabling event.
Fall in rate of stillbirth drives down perinatal mortality
Authors: Anne Gulland
Journal: BMJ (2017)

The rate of perinatal deaths in the UK has declined over two years, largely driven by a drop in rates of stillbirth, according to new figures.1

The report, conducted by the National Perinatal Epidemiology Unit at Oxford University, shows that in 2013 the rate of stillbirth was 4.2 per 1000 deaths. It fell to 3.87 per 1000 in 2015, representing a fall of 8%. The rate of neonatal death fell from 1.84 to 1.74 over the same period, with the rate of extended perinatal death falling from 6.04 to 5.61.

However, the report stressed that, despite the reduction, rates in the UK are higher than in other high income countries.

The data also show strong variation …
Учений-дослідник Дмитро Яворницький у колі медиків
Authors: M.P. Chaban, Z.I. Shevtsova, V.V. Gaponov
Journal: GASTROENTEROLOGY (2017)

Проведено вивчення стосунків дослідника запорозького козацтва академіка Дмитра Яворницького з представниками медичної спільноти. Відображено вплив Д. Яворницького на формування світогляду та громадянської позиції медиків. Наведено відомості про життєвий шлях, професійну та громадську діяльність найбільш колоритних постатей медичних працівників з оточення Дмитра Яворницького.
REGOMA: A randomized, multicenter, controlled open-label phase II clinical trial evaluating regorafenib (REG) activity in relapsed glioblastoma (GBM) patients (PTS).
Authors: Giuseppe Lombardi, Gian Luca De Salvo, Marica Eoli, Alba Ariela Brandes, Roberta Ruda, Marina Faedi, Andrea Pace, Ivan Lolli, Francesco Pasqualetti, Simona Rizzato, Domenico Germano, Evaristo Maiello, Stefano Indraccolo, Giulio Cabrini, Marina Paola Gardiman, Vittorina Zagonel
Journal: Journal of Clinical Oncology (2017)

TPS2085 Background: GBM is the most common and malignant form of primary brain tumor with a high recurrence rate after surgery, radiation therapy and temozolomide. Currently, there is no established regimen for the treatment of recurrent GBM. GBMs are highly vascularized tumors with high expression of pro-angiogenic factors and activation of multiple signaling pathways in the tumor microenvironment, including the receptor tyrosine kinases, VEGFR, FGFR, and PDGFR, which control the tumor vasculature. REG, an oral multikinase inhibitor, inhibits these angiogenic kinases and the mutant oncogenic kinases KIT, RET and B-RAF. REG was demonstrated to be safe and effective in metastatic colon-rectal cancer, hepatocellular carcinoma and GIST PTS. It was shown that REG inhibits tumor angiogenesis and tumor cell proliferation in rat GBM tumor xenografts (Wilhelm S.M, et al. Regorafenib: a new oral multikinase inhibitor of angiogenic, stromal and oncogenic receptor tyrosine kinases with potent preclinical antitumor activity. Int. J. Cancer:129,245-255.2011). Methods: Primary aim of the study is to assess the role of REG activity in prolonging the overall survival in relapsed GBM PTS after surgery and Stupp regimen; secondary aims are to analyze progression free survival, objective response rate, disease control rate and quality of life. Eligible PTS with ECOG PS 0-1, documented progression of disease (after Stupp treatment) as defined by RANO criteria, adequate bone marrow, liver and renal function are randomized in a 1:1 ratio to REG 160 mg/die (3 weeks on, 1 week off) or lomustine 110 mg/m2 (every 6 weeks). A total of 112 PTS will be randomized (α = 0.20, β = 0.20) and stratified based on surgery at recurrence. Disease evaluation is performed with gadolinium brain MRI every 8 weeks according to RANO criteria. Additional exploratory objectives include analysis of specific angiogenic and metabolic biomarkers in tissue as possible predictors of response to REG. The trial started in Nov 2015; as of Jan 2017, 105 PTS have been enrolled. Final analysis is planned in Dec 2017. Clinical trial information: NCT02926222.
Abstract #1940: Prominin1/CD133 marks adult intestinal stem cells that are susceptible to neoplastic transformation
Authors: Liqin Zhu, Paul Gibson, D. Spencer Currle, Yiai Tong, Robert Richardson, Ildar Bayazitov, Helen Poppleton, Stanislav Zakharenko, David Ellison, Richard Gilbertson
Journal: Cancer Research (2009)

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

Cancer stem cells (CSC) are remarkably similar to normal stem cells: both self-renew, are multipotent and express common surface markers, e.g., PROMININ-1 (PROM1, CD133). What remains unclear is whether CSC are the direct progeny of mutated stem cells, or more mature cells that reacquire stem cell properties during tumor formation. Answering this important question will require knowledge of whether normal stem cells are susceptible to cancer causing mutations; however, this has proved difficult to test since the identity of most adult tissue stem cells is not known. Here, using an inducible-Cre-nuclear(n)LacZ reporter allele knocked into the Prom1 locus ( Prom1C-L ), we show that Prom1 is expressed in a variety of developing and adult tissues. Lineage-tracing studies of adult Prom1+/C-L mice containing the Rosa26-YFP reporter allele showed that Prom1+ cells are located at the base of crypts in the small intestine, co-express Lgr5, generate the entire intestinal epithelium, and are therefore likely to be the small intestinal stem cell. Prom1 was reported recently to mark CSC of human intestinal tumors that arise frequently as a consequence of aberrant Wingless (WNT) signaling. Activation of endogenous Wnt signaling in Prom1+/C-L mice containing a Cre-dependent mutant allele of Beta-catenin ( Ctnnb1lox(ex3) ) resulted first in a gross disruption of crypt architecture and a disproportionate expansion of Prom1+ cells at the crypt base. Lineage-tracing demonstrated that the progeny of these cells replaced the mucosa of the entire small intestine with neoplastic tissue that was characterized by focal high-grade intraepithelial neoplasia and crypt adenoma formation. Although all neoplastic cells arose from Prom1+ cells in these mice, only 7% of tumor cells retained Prom1 expression. Our data indicate that Prom1 marks stem cells in the adult small intestine, which are susceptible to transformation into tumors retaining a fraction of mutant-Prom1+ tumor cells.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 1940.
Can exercise influence survival following breast cancer: Results from a randomised, controlled trial.
Authors: Sandra Christine Hayes, Megan Steele, Rosa Spence, Christopher Pyke, Christobel Saunders, John Bashford, Elizabeth Eakin
Journal: Journal of Clinical Oncology (2017)

10067 Background: Exercise for Health was a randomised, controlled trial designed to evaluate an 8-month translational exercise intervention, commencing 6-weeks post-surgery for newly diagnosed breast cancer. Outcomes for this follow-up exploratory analysis were overall- and disease-free survival. Methods: Consenting urban-based women (n = 194) were randomized to one of two exercise groups (intervention delivered either face-to-face or over the telephone) or a usual care group, while consenting rural/regional women (n = 143) were randomised to either the telephone-delivered exercise group or usual care group. For the purposes of these analyses, exercise groups and usual care groups were combined (exercise group, n = 207; usual care group, n = 130). Analyses were done on an intention-to-treat basis and trials were registered with the Australian New Zealand Clinical Trials Registry (ACTRN12606000233527; 12609000809235). Results: Participant disease and treatment characteristics were similar to the wider breast cancer population in Queensland, Australia, and 42% of the sample resided in rural or regional areas. After a median follow-up of 101 months, there were 15/130 (11.5%) survival events in the usual care group, compared with 11/207 (5.3%) events in the exercise group. Disease-free events for the usual care versus exercise group were 23/130 (17.7%) and 25/207 (12.1%), respectively. The corresponding unadjusted hazard ratio for the exercise group for overall survival was 0.45 (95% CI = 0.21-0.97; p = 0.037), and for disease-free survival was 0.66 (95% CI = 0.38-1.17; p = 0.155). Conclusions: Epidemiological evidence consistently shows a positive relationship between physical activity and survival post-breast cancer, but is unable to establish causality. These exploratory findings suggest that an exercise intervention delivered during and beyond conventional treatment for breast cancer and that was designed to cater for all women, irrespective of place of residence and access to medical services, has clear potential to influence survival. Clinical trial information: ACTRN12606000233527; 12609000809235.